FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Tassa, C Liong, M Hilderbrand, S Sandler, JE Reiner, T Keliher, EJ Weissleder, R Shaw, SY AF Tassa, C. Liong, M. Hilderbrand, S. Sandler, J. E. Reiner, T. Keliher, E. J. Weissleder, R. Shaw, S. Y. TI On-chip bioorthogonal chemistry enables immobilization of in situ modified nanoparticles and small molecules for label-free monitoring of protein binding and reaction kinetics SO LAB ON A CHIP LA English DT Article ID SURFACE-PLASMON RESONANCE; CLICK CHEMISTRY; LIVING CELLS; TAT PEPTIDE; CYCLOADDITION; BIOCONJUGATION; PROBES; CONJUGATION; SENSITIVITY; INHIBITORS AB Efficient methods to immobilize small molecules under continuous-flow microfluidic conditions would greatly improve label-free molecular interaction studies using biosensor technology. At present, small-molecule immobilization chemistries require special conditions and in many cases must be performed outside the detector and microfluidic system where real-time monitoring is not possible. Here, we have developed and optimized a method for on-chip bioorthogonal chemistry that enables rapid, reversible immobilization of small molecules with control over orientation and immobilization density, and apply this technique to surface plasmon resonance (SPR) studies. Immobilized small molecules reverse the orientation of canonical SPR interaction studies, and also enable a variety of new SPR applications including on-chip assembly and interaction studies of multicomponent structures, such as functionalized nanoparticles, and measurement of bioorthogonal reaction rates. We use this approach to demonstrate that on-chip assembled functionalized nanoparticles show a preserved ability to interact with their target protein, and to measure rapid bioorthogonal reaction rates with k(2) > 10(3) M-1 s(-1). This method offers multiple benefits for microfluidic biological applications, including rapid screening of targeted nanoparticles with vastly decreased nanoparticle synthetic requirements, robust immobilization chemistry in the presence of serum, and a continuous flow technique that mimics biologic contexts better than current methods used to measure bioorthogonal reaction kinetics such as NMR or UV-vis spectroscopy (e. g., stopped flow kinetics). Taken together, this approach constitutes a flexible and powerful technique for evaluating a wide variety of reactions and intermolecular interactions for in vitro or in vivo applications. C1 [Weissleder, R.] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Weissleder, R (reprint author), Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. EM rweissleder@mgh.harvard.edu; shaw.stanley@mgh.harvard.edu OI Reiner, Thomas/0000-0002-7819-5480 FU NIH (NHLBI) [HHSN268201000044C] FX We thank Nikolay Sergeyev for providing the cross-linked magnetic nanoparticles, Mark Karver and Jenna A. Klubnick for reagents, and Paul Belcher (GE Healthcare) for SPR technical support. We acknowledge funding from NIH (NHLBI Contract No. HHSN268201000044C to R. W., S. H. and S.Y.S.). NR 58 TC 16 Z9 16 U1 1 U2 47 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 1473-0197 J9 LAB CHIP JI Lab Chip PY 2012 VL 12 IS 17 BP 3103 EP 3110 DI 10.1039/c2lc40337d PG 8 WC Biochemical Research Methods; Chemistry, Multidisciplinary; Nanoscience & Nanotechnology SC Biochemistry & Molecular Biology; Chemistry; Science & Technology - Other Topics GA 982ST UT WOS:000307066400019 PM 22760641 ER PT J AU Chen, GD Fachin, F Colombini, E Wardle, BL Toner, M AF Chen, Grace D. Fachin, Fabio Colombini, Elena Wardle, Brian L. Toner, Mehmet TI Nanoporous micro-element arrays for particle interception in microfluidic cell separation SO LAB ON A CHIP LA English DT Article ID CYLINDRICAL COLLECTOR; REYNOLDS-NUMBERS; FLOW; CYLINDER; CAPTURE; SUSPENSION; MEMBRANES; FLUID AB The ability to control cell-surface interactions in order to achieve binding of specific cell types is a major challenge for microfluidic immunoaffinity cell capture systems. In the majority of existing systems, the functionalized capture surface is constructed of solid materials, where flow stagnation at the solid-liquid interface is detrimental to the convection of cells to the surface. We study the use of ultra-high porosity (99%) nanoporous micro-posts in microfluidic channels for enhancing interception efficiency of particles in flow. We show using both modelling and experiment that nanoporous posts improve particle interception compared to solid posts through two distinct mechanisms: the increase of direct interception, and the reduction of near-surface hydrodynamic resistance. We provide initial validation that the improvement of interception efficiency also results in an increase in capture efficiency when comparing nanoporous vertically aligned carbon nanotube (VACNT) post arrays with solid PDMS post arrays of the same geometry. Using both bacteria (similar to 1 mu m) and cancer cell lines (similar to 15 mu m) as model systems, we found capture efficiency increases by 6-fold and 4-fold respectively. The combined model and experimental platform presents a new generation of nanoporous microfluidic devices for cell isolation. C1 [Chen, Grace D.; Fachin, Fabio; Toner, Mehmet] Massachusetts Gen Hosp, BioMEMS Resource Ctr, Charlestown, MA 02129 USA. [Fachin, Fabio; Colombini, Elena; Wardle, Brian L.] MIT, Dept Aeronaut & Astronaut, Cambridge, MA 02139 USA. [Colombini, Elena] Univ Modena & Reggio Emilia, Dept Mat & Environm Engn DIMA, Modena, Italy. RP Toner, M (reprint author), Massachusetts Gen Hosp, BioMEMS Resource Ctr, Charlestown, MA 02129 USA. EM mtoner@hms.harvard.edu FU National Institute of Biomedical Imaging and Bioengineering [P41 EB002503]; MRSEC Program of the National Science Foundation [DMR-0819762]; U.S. Department of State's Fulbright Science and Technology Award; Massachusetts Institute of Technology's Nano-Engineered Composite aerospace Structures (NECST) Consortium; National Science Foundation [DMR-0819762] FX We thank Octavio Hurtado and Namiko Yamamoto for technical support with nano- and micro-fabrication procedures. This work was supported by the National Institute of Biomedical Imaging and Bioengineering under Grant No. P41 EB002503, the MRSEC Program of the National Science Foundation under award number DMR-0819762, and U.S. Department of State's Fulbright Science and Technology Award. Materials used in this work were the result of work sponsored by the Massachusetts Institute of Technology's Nano-Engineered Composite aerospace Structures (NECST) Consortium. This work made use of the MRSEC shared experimental facilities supported by the National Science Foundation under award number DMR-0819762 and was carried out in part through the use of MIT's Microsystems Technology Laboratories. NR 38 TC 9 Z9 10 U1 1 U2 37 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 1473-0197 J9 LAB CHIP JI Lab Chip PY 2012 VL 12 IS 17 BP 3159 EP 3167 DI 10.1039/c2lc40109f PG 9 WC Biochemical Research Methods; Chemistry, Multidisciplinary; Nanoscience & Nanotechnology SC Biochemistry & Molecular Biology; Chemistry; Science & Technology - Other Topics GA 982ST UT WOS:000307066400026 PM 22763858 ER PT J AU Leung, FW Aljebreen, A AF Leung, Felix W. Aljebreen, Abdulrahman TI Health Care Providers' Acceptance of Unsedated Colonoscopy Before and After a State-of-the-art Lecture on the Feasibility of the Option SO SAUDI JOURNAL OF GASTROENTEROLOGY LA English DT Article DE Acceptance; health care providers; unsedated colonoscopy ID SEDATION; ENDOSCOPY; VETERANS AB Background/Aim: The impact of education on acceptance of unsedated colonoscopy by health care providers is unknown. To test the hypothesis that knowledge imparted by a lecture on unsedated colonoscopy is associated with its enhanced acceptance. Settings and Design: At the State-of-the-Art Lecture on "Unsedated colonoscopy: Is it feasible?" presented at the 8th Pan-Arab Conference on Gastroenterology, February, 2011, Riyadh, Saudi Arabia, a questionnaire survey of the audience was undertaken. Materials and Methods: An expectation questionnaire was administered before and after the lecture. Attendees responded anonymously. Statistical analysis used: The responses of a convenient sample of 49 attendees who provided completed responses to the questionnaire both before and after the lecture were analyzed. Data are expressed as frequency counts and means +/- SEM. Repeated measures analysis of variance (ANOVA), ANOVA with contrasts and Chi-square analysis (Statview II Program for Macintosh computers) were used to assess the data. A P value of <0.05 is considered significant. Results and Conclusions: The mean +/- SEM credibility score (maximum possible score=50) was 25.8 +/- 1.8 before and 33.3 +/- 2.1 after the lecture, with a significant improvement in mean score of 7.5 +/- 1.3 (P=0.001, paired t test). Nineteen (39%) respondents were not willing to consider unsedated colonoscopy for themselves before the lecture. This number decreased to 13 (27%) after the lecture. Before the lecture only 4(8%) respondents were willing to consider unsedated colonoscopy for themselves. After the lecture this number increased to 8(16%). The data suggest education of healthcare professionals regarding the feasibility of unsedated colonoscopy appears to enhance its acceptance as a credible patient care option at a Pan-Arab Gastroenterology Conference. C1 [Leung, Felix W.] VA Greater Los Angeles Healthcare Syst, Sepulveda Ambulatory Care Ctr, Res Serv, Los Angeles, CA USA. [Leung, Felix W.] VA Greater Los Angeles Healthcare Syst, Sepulveda Ambulatory Care Ctr, Med Serv, Los Angeles, CA USA. [Leung, Felix W.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Aljebreen, Abdulrahman] King Khalid Univ Hosp, KSU, Riyadh 11472, Saudi Arabia. RP Leung, FW (reprint author), VAGLAHS, Sepulveda Ambulatory Care Ctr, 111G,16111 Plummer St, North Hills, CA 91343 USA. EM felixleung@socal.rr.com FU ACG Clinical Research Award; ASGE Career Development Award; Veterans Affairs Greater Los Angeles Healthcare System medical research funds FX Supported in part by 2009 ACG Clinical Research Award, 1985 ASGE Career Development Award, and Veterans Affairs Greater Los Angeles Healthcare System medical research funds. NR 18 TC 0 Z9 0 U1 0 U2 0 PU MEDKNOW PUBLICATIONS PI MUMBAI PA B-9, KANARA BUSINESS CENTRE, OFF LINK RD, GHAKTOPAR-E, MUMBAI, 400075, INDIA SN 1319-3767 J9 SAUDI J GASTROENTERO JI Saudi J. Gastroenterol. PD JAN-FEB PY 2012 VL 18 IS 1 BP 50 EP 54 DI 10.4103/1319-3767.91736 PG 5 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 980JZ UT WOS:000306890800010 PM 22249093 ER PT J AU Wadlow, R Hezel, AF Abrams, TA Blaszkowsky, LS Fuchs, CS Kulke, MH Kwak, EL Meyerhardt, JA Ryan, DP Szymonifka, J Wolpin, BM Zhu, AX Clark, JW AF Wadlow, Raymond Hezel, Aram F. Abrams, Thomas A. Blaszkowsky, Lawrence S. Fuchs, Charles S. Kulke, Matthew H. Kwak, Eunice L. Meyerhardt, Jeffrey A. Ryan, David P. Szymonifka, Jackie Wolpin, Brian M. Zhu, Andrew X. Clark, Jeffrey W. TI Panitumumab in Patients with KRAS Wild-Type Colorectal Cancer after Progression on Cetuximab SO ONCOLOGIST LA English DT Article ID 1ST-LINE TREATMENT; INFUSION REACTIONS; CHEMOTHERAPY; OXALIPLATIN; MONOTHERAPY; BEVACIZUMAB; IRINOTECAN; EFFICACY; THERAPY; SAFETY C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Dana Farber Canc Inst, Boston, MA USA. RP Wadlow, R (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. RI Inov Farmaceutica, Inct/K-2313-2013 FU Dana-Farber Cancer Institute [NCT00842257]; Massachusetts General Hospital [NCT00842257]; Amgen, Inc [NCT00842257] FX ClinicalTrials.gov Identifier NCT00842257 Sponsor(s) Amgen, Inc., Massachusetts General Hospital, and Dana-Farber Cancer Institute NR 26 TC 30 Z9 30 U1 0 U2 3 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1083-7159 J9 ONCOLOGIST JI Oncologist PD JAN PY 2012 VL 17 IS 1 BP E27 EP E35 DI 10.1634/theoncologist.2011-0452 PG 9 WC Oncology SC Oncology GA 887UG UT WOS:000299955500022 PM 22210091 ER PT J AU Pisano, DV Niesten, MEF Merchant, SN Nakajima, HH AF Pisano, Dominic V. Niesten, Marlien E. F. Merchant, Saumil N. Nakajima, Hideko Heidi TI The Effect of Superior Semicircular Canal Dehiscence on Intracochlear Sound Pressures SO AUDIOLOGY AND NEURO-OTOLOGY LA English DT Article DE Superior semicircular canal dehiscence; Cochlear pressure; Scala vestibuli; Scala tympani; Cochlea; Differential pressure ID CONDUCTIVE HEARING-LOSS; INNER-EAR MECHANICS; MIDDLE-EAR; CHINCHILLA AB Semicircular canal dehiscence (SCD) is a pathological opening in the bony wall of the inner ear that can result in conductive hearing loss. The hearing loss is variable across patients, and the precise mechanism and source of variability are not fully understood. Simultaneous measurements of basal intracochlear sound pressures in scala vestibuli (SV) and scala tympani (ST) enable quantification of the differential pressure across the cochlear partition, the stimulus that excites the cochlear partition. We used intracochlear sound pressure measurements in cadaveric preparations to study the effects of SCD size. Sound-induced pressures in SV and ST, as well as stapes velocity and ear canal pressure were measured simultaneously for various sizes of SCD followed by SCD patching. Our results showed that at low frequencies (<600 Hz), SCD decreased the pressure in both SV and ST, as well as differential pressure, and these effects became more pronounced as dehiscence size was increased. Near 100 Hz, SV decreased by about 10 dB for a 0.5-mm dehiscence and by 20 dB for a 2-mm dehiscence, while ST decreased by about 8 dB for a 0.5-mm dehiscence and by 18 dB for a 2-mm dehiscence. Differential pressure decreased by about 10 dB for a 0.5-mm dehiscence and by about 20 dB for a 2-mm dehiscence at 100 Hz. In some ears, for frequencies above 1 kHz, the smallest pinpoint dehiscence had bigger effects on the differential pressure (10-dB decrease) than larger dehiscences (less than 10-dB decrease), suggesting larger hearing losses in this frequency range. These effects due to SCD were reversible by patching the dehiscence. We also showed that under certain circumstances such as SCD, stapes velocity is not related to how the ear can transduce sound across the cochlear partition because it is not directly related to the differential pressure, emphasizing that certain pathologies cannot be fully assessed by measurements such as stapes velocity. Copyright (C) 2012 S. Karger AG, Basel C1 [Pisano, Dominic V.; Merchant, Saumil N.; Nakajima, Hideko Heidi] Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA. [Niesten, Marlien E. F.; Merchant, Saumil N.; Nakajima, Hideko Heidi] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. [Merchant, Saumil N.; Nakajima, Hideko Heidi] Harvard MIT Div Hlth Sci & Technol, Speech & Hearing Biosci & Technol Program, Cambridge, MA USA. [Niesten, Marlien E. F.] Univ Med Ctr, Dept Otorhinolaryngol Head & Neck Surg, Utrecht, Netherlands. RP Nakajima, HH (reprint author), Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, 243 Charles St, Boston, MA 02114 USA. EM heidi_nakajima@meei.harvard.edu FU NIH [R03DC011158, R01DC004798] FX John Rosowski kindly provided advice on this project and manuscript. We thank Diane Jones, Mike Ravicz, and Ishmael Stefanov-Wagner and the other staff of the Otolaryngology Department and Eaton Peabody Laboratory for their generous contributions. We are also indebted to Lisa Olson for consulting on our work and providing expertise regarding the fiberoptic micro pressure transducers. This work was carried out in part through the use of MIT's Microsystems Technology Laboratories for the fabrication of the micro fiberoptic pressure sensors. Support was provided by NIH grants R03DC011158 (H.H.N.) and R01DC004798 (S.N.M.). NR 18 TC 17 Z9 17 U1 0 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1420-3030 J9 AUDIOL NEURO-OTOL JI Audiol. Neuro-Otol. PY 2012 VL 17 IS 5 BP 338 EP 348 DI 10.1159/000339653 PG 11 WC Audiology & Speech-Language Pathology; Neurosciences; Otorhinolaryngology SC Audiology & Speech-Language Pathology; Neurosciences & Neurology; Otorhinolaryngology GA 977RT UT WOS:000306682800008 PM 22814034 ER PT J AU Hayes, SM Verfaellie, M AF Hayes, Scott M. Verfaellie, Mieke TI The impact of fluency on explicit memory tasks in amnesia SO COGNITIVE NEUROSCIENCE LA English DT Editorial Material AB Distinguishing implicit and explicit memory and delineating their relationship has haunted memory researchers for decades, and Voss et al. provide an impressive overview of their work examining these issues. We briefly comment on the following: (1) There is evidence indicating that implicit memory impacts cued recall, in addition to recognition; (2) Fluency can manifest as priming in implicit memory or it can be experienced as familiarity (in association with attribution processes) in recognition tasks; and (3) The impact of fluency on accuracy of "guess" responses during recognition memory in normal subjects is reminiscent of similar effects on recognition in amnesia. C1 [Hayes, Scott M.; Verfaellie, Mieke] VA Boston Healthcare Syst, Memory Disorders Res Ctr, Boston, MA USA. [Hayes, Scott M.; Verfaellie, Mieke] Boston Univ, Sch Med, Boston, MA 02118 USA. [Hayes, Scott M.] VA Boston Healthcare Syst, Neuroimaging Res Ctr, Boston, MA USA. RP Hayes, SM (reprint author), VA Boston Healthcare Syst, Memory Disorders Res Ctr, Boston, MA USA. EM smhayes@bu.edu FU Department of Veteran Affairs Rehabilitation Research and Development Service; Department of Veteran Affairs Clinical Science Research and Development Service FX This work was supported by the Department of Veterans Affairs Rehabilitation Research and Development Service and Clinical Science Research and Development Service. NR 0 TC 2 Z9 3 U1 0 U2 5 PU PSYCHOLOGY PRESS PI HOVE PA 27 CHURCH RD, HOVE BN3 2FA, EAST SUSSEX, ENGLAND SN 1758-8928 J9 COGN NEUROSCI-UK JI Cogn. Neurosci PY 2012 VL 3 IS 3-4 SI SI BP 216 EP 217 DI 10.1080/17588928.2012.689974 PG 2 WC Neurosciences SC Neurosciences & Neurology GA 979QJ UT WOS:000306834600015 PM 24171743 ER PT J AU Hassman, H Targum, SD Fava, M Pinho, M AF Hassman, H. Targum, S. D. Fava, M. Pinho, M. TI VALIDATION OF A GLOBAL ASSESSMENT MEASURE FOR FATIGUE SO EUROPEAN PSYCHIATRY LA English DT Meeting Abstract C1 [Hassman, H.; Pinho, M.] CRI Worldwide, Mt Laurel, NJ USA. [Targum, S. D.; Fava, M.] Clintara LLC, Boston, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER PI PARIS PA 23 RUE LINOIS, 75724 PARIS, FRANCE SN 0924-9338 J9 EUR PSYCHIAT JI Eur. Psychiat. PY 2012 VL 27 SU 1 MA P-862 PG 1 WC Psychiatry SC Psychiatry GA 977WL UT WOS:000306695401482 ER PT J AU Joshi, G Biederman, J Petty, C Goldin, RL Wozniak, J AF Joshi, G. Biederman, J. Petty, C. Goldin, R. L. Wozniak, J. TI EXAMINING THE COMORBIDITY OF BIPOLAR DISORDER AND AUTISM SPECTRUM DISORDERS: A LARGE CONTROLLED ANALYSIS OF PHENOTYPIC AND FAMILIAL CORRELATES IN YOUTH WITH BIPOLAR DISORDER SO EUROPEAN PSYCHIATRY LA English DT Meeting Abstract C1 [Joshi, G.; Biederman, J.; Petty, C.; Goldin, R. L.; Wozniak, J.] Massachusetts Gen Hosp, Cambridge, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 6 PU ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER PI PARIS PA 23 RUE LINOIS, 75724 PARIS, FRANCE SN 0924-9338 J9 EUR PSYCHIAT JI Eur. Psychiat. PY 2012 VL 27 SU 1 MA O-22 PG 1 WC Psychiatry SC Psychiatry GA 977WL UT WOS:000306695400173 ER PT J AU Wilkinson, CW Peskind, ER Pagulayan, KF Colasurdo, EA Shofer, JB AF Wilkinson, C. W. Peskind, E. R. Pagulayan, K. F. Colasurdo, E. A. Shofer, J. B. TI CHRONIC PITUITARY DYSFUNCTION ASSOCIATED WITH COGNITIVE AND NEUROPSYCHIATRIC DEFICITS AFTER BLAST-RELATED MILD TRAUMATIC BRAIN INJURY SO EUROPEAN PSYCHIATRY LA English DT Meeting Abstract C1 VA Puget Sound Hlth Care Syst, Geriatr Res Educ & Clin Ctr, Seattle, WA USA. Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. VA Puget Sound Hlth Care Syst, Educ & Clin Ctr, NW Network Mental Illness Res, Seattle, WA USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER PI PARIS PA 23 RUE LINOIS, 75724 PARIS, FRANCE SN 0924-9338 J9 EUR PSYCHIAT JI Eur. Psychiat. PY 2012 VL 27 SU 1 MA P-985 PG 1 WC Psychiatry SC Psychiatry GA 977WL UT WOS:000306695402007 ER PT J AU Song, JW Bazou, D Munn, LL AF Song, Jonathan W. Bazou, Despina Munn, Lance L. TI Anastomosis of endothelial sprouts forms new vessels in a tissue analogue of angiogenesis SO INTEGRATIVE BIOLOGY LA English DT Article ID MICROFLUIDIC PLATFORM; MOLECULAR-MECHANISMS; NETWORK FORMATION; GROWTH-FACTORS; IN-VITRO; CELL; CANCER; VEGF; MORPHOGENESIS; FABRICATION AB Here we describe a microfluidic device that accurately reproduces the dynamics of vascular anastomosis, the process by which vascular sprouts connect to achieve perfusion during angiogenesis. The micro-device features two parallel endothelial cell-lined vessel analogues separated by a 300 mu m wide collagenous matrix into which the vessels can sprout and form perfused bridging connections. By accurately recapitulating anastomosis in vitro, the device will enable a new generation of studies of the mechanisms of angiogenesis and provide a novel and practical platform for drug screening. C1 [Song, Jonathan W.] Massachusetts Gen Hosp, Edwin L Steele Lab Tumour Biol, Dept Radiat Oncol, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. RP Song, JW (reprint author), Massachusetts Gen Hosp, Edwin L Steele Lab Tumour Biol, Dept Radiat Oncol, Charlestown, MA 02129 USA. EM munn@steele.mgh.harvard.edu RI Munn, Lance/L-3950-2016; Song, Jonathan/C-1922-2013 OI Munn, Lance/0000-0003-0698-7232; Song, Jonathan/0000-0002-6991-5298 FU National Cancer Institute [NIH R01CA149285, R21CA12676-02, T32CA073479] FX The authors would like to acknowledge funding from the National Cancer Institute (NIH R01CA149285, R21CA12676-02, and T32CA073479). We thank Abhishek Jain for his helpful discussions. NR 43 TC 40 Z9 40 U1 3 U2 25 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 1757-9694 J9 INTEGR BIOL-UK JI Integr. Biol. PY 2012 VL 4 IS 8 BP 857 EP 862 DI 10.1039/c2ib20061a PG 6 WC Cell Biology SC Cell Biology GA 978AA UT WOS:000306708500004 PM 22673771 ER PT J AU Claunch, JD Chan, ST Nixon, EE Qiu, WQ Sporko, T Dunn, JP Kwong, KK Hui, KKS AF Claunch, Joshua D. Chan, Suk-Tak Nixon, Erika E. Qiu, Wei Qiao Sporko, Tara Dunn, Joseph P. Kwong, Kenneth K. Hui, Kathleen K. S. TI Commonality and Specificity of Acupuncture Action at Three Acupoints as Evidenced by fMRI SO AMERICAN JOURNAL OF CHINESE MEDICINE LA English DT Article DE Acupuncture; fMRI; Limbic-Paralimbic-Neocortical Network; Default Mode; Acupoint Specificity; Deqi ID POSTTRAUMATIC-STRESS-DISORDER; HUMAN CINGULATE CORTEX; FUNCTIONAL MRI; HUMAN BRAIN; ANTIDEPRESSANT TREATMENT; AMYGDALA ACTIVATION; MANUAL ACUPUNCTURE; PANIC DISORDER; LIMBIC SYSTEM; DEFAULT MODE AB Previous work from our team and others has shown that manual acupuncture at LI4 (hegu), ST36 (zusanli), and LV3 (taichong) deactivates a limbic-paralimbic-neocortical brain network, and at the same time activates somatosensory regions of the brain. The objective of the present study was to explore the specificity and commonality of the brain response to manual acupuncture at LI4, ST36, and LV3, acupoints that are located on different meridians and are used to treat pain disorders. We used functional magnetic resonance imaging (fMRI) to monitor the brain responses to acupuncture at three different acupoints; we examined 46 healthy subjects who, according to their psychophysical responses, experienced deqi sensation during acupuncture. Brain responses to stimulation at each of the acupoints were displayed in conjunction with one another to show the spatial distribution. We found clusters of deactivation in the medial prefrontal, medial parietal and medial temporal lobes showing significant convergence of two or all three of the acupoints. The largest regions showing common responses to all three acupoints were the right subgenual BA25, right subgenual cingulate, right isthmus of the cingulum bundle, and right BA31. We also noted differences in major sections of the medial prefrontal and medial temporal lobes, with LI4 predominating in the pregenual cingulate and hippocampal formation, ST36 predominating in the subgenual cingulate, and LV3 predominating in the posterior hippocampus and posterior cingulate. The results suggest that although these acupoints are commonly used for anti-pain and modulatory effects, they may mobilize the same intrinsic global networks, with substantial overlap of common brain regions to mediate their actions. Our findings showing preferential response of certain limbic-paralimbic structures suggests acupoints may also exhibit relative specificity. C1 [Claunch, Joshua D.; Chan, Suk-Tak; Nixon, Erika E.; Sporko, Tara; Kwong, Kenneth K.; Hui, Kathleen K. S.] Massachusetts Gen Hosp, Dept Radiol, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. [Claunch, Joshua D.; Chan, Suk-Tak; Nixon, Erika E.; Sporko, Tara; Kwong, Kenneth K.; Hui, Kathleen K. S.] Harvard Univ, Sch Med, Charlestown, MA USA. [Qiu, Wei Qiao] Boston Univ, Dept Psychiat, Boston, MA 02215 USA. [Dunn, Joseph P.] Boston Coll, Chestnut Hill, MA 02167 USA. RP Chan, ST (reprint author), Massachusetts Gen Hosp, Dept Radiol, Athinoula A Martinos Ctr Biomed Imaging, 149 13th St, Charlestown, MA 02129 USA. EM phoebe@nmr.mgh.harvard.edu RI Chan, Suk-tak/G-5846-2015 FU National Institutes of Health/National Center for Complementary and Alternative Medicine [R21AT00978, P01AT002048]; National Center for Research Resources [P41RR14075]; National Institute of Neurological Disorders and Stroke [R01NS34189] FX The work was supported in part by the National Institutes of Health/National Center for Complementary and Alternative Medicine (R21AT00978, P01AT002048) and the National Center for Research Resources (P41RR14075), and the National Institute of Neurological Disorders and Stroke (R01NS34189). NR 70 TC 15 Z9 17 U1 2 U2 16 PU WORLD SCIENTIFIC PUBL CO PTE LTD PI SINGAPORE PA 5 TOH TUCK LINK, SINGAPORE 596224, SINGAPORE SN 0192-415X J9 AM J CHINESE MED JI Am. J. Chin. Med. PY 2012 VL 40 IS 4 BP 695 EP 712 DI 10.1142/S0192415X12500528 PG 18 WC Integrative & Complementary Medicine; Medicine, General & Internal SC Integrative & Complementary Medicine; General & Internal Medicine GA 976NL UT WOS:000306591500004 PM 22809025 ER PT J AU Hipp, J Monaco, J Kunju, LP Cheng, J Yagi, Y Rodriguez-Canales, J Emmert-Buck, MR Hewitt, S Feldman, MD Tomaszewski, JE Toner, M Tompkins, RG Flotte, T Lucas, D Gilbertson, JR Madabhushi, A Balis, U AF Hipp, Jason Monaco, James Kunju, L. Priya Cheng, Jerome Yagi, Yukako Rodriguez-Canales, Jaime Emmert-Buck, Michael R. Hewitt, Stephen Feldman, Michael D. Tomaszewski, John E. Toner, Mehmet Tompkins, Ronald G. Flotte, Thomas Lucas, David Gilbertson, John R. Madabhushi, Anant Balis, Ulysses TI Integration of architectural and cytologic driven image algorithms for prostate adenocarcinoma identification SO ANALYTICAL CELLULAR PATHOLOGY LA English DT Article DE Pathology informatics; whole slide imaging; computer aided diagnosis; SIVQ; PPMM; digital imaging; prostate cancer; cancer ID RADICAL PROSTATECTOMY; INDEPENDENT PREDICTOR; ANTIGEN RECURRENCE; CANCER; CARCINOMA; TUMOR; PERCENTAGE; SPECIMENS; PATHOLOGY; DIAMETER AB Introduction: The advent of digital slides offers new opportunities within the practice of pathology such as the use of image analysis techniques to facilitate computer aided diagnosis (CAD) solutions. Use of CAD holds promise to enable new levels of decision support and allow for additional layers of quality assurance and consistency in rendered diagnoses. However, the development and testing of prostate cancer CAD solutions requires a ground truth map of the cancer to enable the generation of receiver operator characteristic (ROC) curves. This requires a pathologist to annotate, or paint, each of the malignant glands in prostate cancer with an image editor software - a time consuming and exhaustive process. Recently, two CAD algorithms have been described: probabilistic pairwise Markov models (PPMM) and spatially-invariant vector quantization (SIVQ). Briefly, SIVQ operates as a highly sensitive and specific pattern matching algorithm, making it optimal for the identification of any epithelial morphology, whereas PPMM operates as a highly sensitive detector of malignant perturbations in glandular lumenal architecture. Methods: By recapitulating algorithmically how a pathologist reviews prostate tissue sections, we created an algorithmic cascade of PPMM and SIVQ algorithms as previously described by Doyle el al. [1] where PPMM identifies the glands with abnormal lumenal architecture, and this area is then screened by SIVQ to identify the epithelium. Results: The performance of this algorithm cascade was assessed qualitatively (with the use of heatmaps) and quantitatively (with the use of ROC curves) and demonstrates greater performance in the identification of malignant prostatic epithelium. Conclusion: This ability to semi-autonomously paint nearly all the malignant epithelium of prostate cancer has immediate applications to future prostate cancer CAD development as a validated ground truth generator. In addition, such an approach has potential applications as a pre-screening/quality assurance tool. C1 [Hipp, Jason; Kunju, L. Priya; Cheng, Jerome; Lucas, David; Balis, Ulysses] Univ Michigan, Dept Pathol, Catherine, MI USA. [Monaco, James; Madabhushi, Anant] Rutgers State Univ, Dept Biomed Engn, Piscataway, NJ USA. [Yagi, Yukako] MGH Pathol Imaging & Commun Technol PICT Ctr, Boston, MA USA. [Rodriguez-Canales, Jaime; Emmert-Buck, Michael R.; Hewitt, Stephen] NCI, Pathol Lab, NIH, Adv Technol Ctr, Gaithersburg, MD USA. [Flotte, Thomas] Mayo Clin, Dept Lab Med & Pathol, Rochester, MN USA. [Toner, Mehmet; Tompkins, Ronald G.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Charlestown, MA USA. [Gilbertson, John R.] Harvard Univ, Sch Med, Dept Pathol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Feldman, Michael D.] Univ Penn, Dept Pathol & Lab Med, Perlman Sch Med, Div Surg Pathol,Founders Hosp 6, Philadelphia, PA 19104 USA. [Tomaszewski, John E.] SUNY Buffalo, Sch Med & Biomed Sci, Buffalo, NY 14260 USA. RP Balis, U (reprint author), Univ Michigan Hlth Syst, Dept Pathol, M4233A Med Sci 1,1301 Catherine, Ann Arbor, MI 48109 USA. EM anantm@rci.rutgers.edu; Ulysses@med.umich.edu OI Rodriguez-Canales, Jaime/0000-0002-0885-2377; Hewitt, Stephen/0000-0001-8283-1788 FU Wallace H. Coulter Foundation; National Cancer Institute [R01CA136535-01, R03CA143991-01]; Burroughs Wellcome Fund; Center for Cancer Research of the National Cancer Institute, NIH, Bethesda, MD FX This work was made possible via grants from the Wallace H. Coulter Foundation, National Cancer Institute (Grant Nos. R01CA136535-01 and R03CA143991-01), and Burroughs Wellcome Fund (Collaborative Research Travel Grant) supported in part by the Center for Cancer Research of the National Cancer Institute, NIH, Bethesda, MD. NR 29 TC 6 Z9 6 U1 0 U2 6 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 2210-7177 J9 ANAL CELL PATHOL JI Anal. Cell. Pathol. PY 2012 VL 35 IS 4 BP 251 EP 265 DI 10.3233/ACP-2012-0054 PG 15 WC Oncology; Cell Biology; Pathology SC Oncology; Cell Biology; Pathology GA 976AO UT WOS:000306553100003 PM 22425661 ER PT J AU Nishimori, M Low, JHS Zheng, H Ballantyne, JC AF Nishimori, Mina Low, James H. S. Zheng, Hui Ballantyne, Jane C. TI Epidural pain relief versus systemic opioid-based pain relief for abdominal aortic surgery SO COCHRANE DATABASE OF SYSTEMATIC REVIEWS LA English DT Review DE Analgesia, Epidural [adverse effects; methods]; Analgesics, Opioid [adverse effects; therapeutic use]; Aorta, Abdominal [surgery]; Cause of Death; Intubation, Intratracheal; Pain, Postoperative [prevention & control]; Postoperative Complications [mortality]; Adult; Humans ID PATIENT-CONTROLLED ANALGESIA; ENDOVASCULAR-ANEURYSM-REPAIR; RANDOMIZED CONTROLLED-TRIAL; PLUS GENERAL-ANESTHESIA; POSTOPERATIVE ANALGESIA; MAJOR SURGERY; SURGICAL STRESS; BYPASS-SURGERY; FUNNEL PLOT; BUPIVACAINE AB Background Epidural analgesia offers greater pain relief compared to systemic opioid-based medications, but its effect on morbidity and mortality is unclear. This review was originally published in 2006 and was updated in 2011. Objectives To assess the benefits and harms of postoperative epidural analgesia in comparison with postoperative systemic opioid-based pain relief for adult patients who underwent elective abdominal aortic surgery. Search methods We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2010, Issue 11) via Ovid; Ovid MEDLINE (from inception to week 1 November 2010); and EMBASE (from inception to week 1, November 2010). The original search was performed in 2004. We assessed non-English language reports and contacted researchers in the field. We did not seek unpublished data. Selection criteria We included all randomized and quasi-randomized controlled trials comparing postoperative epidural analgesia and postoperative systemic opioid-based analgesia for adult patients who underwent elective open abdominal aortic surgery. Data collection and analysis Two authors independently assessed trial quality and extracted data. We contacted study authors for additional information and data. Main results We included 15 trials that involved 1297 patients (633 patients received epidural analgesia and 664 received systemic opioid analgesia) in this review. This included one trial we found in our updated search and one trial from our original review that had been awaiting translation. The epidural analgesia group showed significantly lower visual analogue scale scores for pain on movement (up to postoperative day three) regardless of the site of the epidural catheter and epidural formulation. The postoperative duration of tracheal intubation and mechanical ventilation was significantly shorter, by about 48%, in the epidural analgesia group. The overall event rates of myocardial infarction, acute respiratory failure (defined as an extended need for mechanical ventilation), gastrointestinal complications, and renal complications were significantly lower in the epidural analgesia group. Authors' conclusions Epidural analgesia provides better pain relief (especially during movement) in the period up to three postoperative days. It reduces the duration of postoperative tracheal intubation by roughly half. The occurrence of prolonged postoperative mechanical ventilation, myocardial infarction, gastric complications and renal complications was reduced by epidural analgesia. However, current evidence does not confirm the beneficial effect of epidural analgesia on postoperative mortality and other types of complications. C1 [Nishimori, Mina] Univ Tokyo, Dept Anesthesiol, Bunkyo Ku, Tokyo, Japan. [Low, James H. S.] So Derbyshire Acute Hosp NHS Trust Derbyshire Roy, Dept Anaesthesia & Crit Care, Derby DE1 2QY, England. [Zheng, Hui] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Biostat, Boston, MA USA. [Ballantyne, Jane C.] Univ Washington, Dept Anesthesiol & Pain Med, Seattle, WA 98195 USA. RP Nishimori, M (reprint author), Univ Tokyo, Dept Anesthesiol, Bunkyo Ku, Tokyo, Japan. EM Minansm@aol.com FU Japan Society for Promotion of Science, Japan FX External sources; Japan Society for Promotion of Science, Japan. NR 95 TC 9 Z9 9 U1 0 U2 7 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1469-493X J9 COCHRANE DB SYST REV JI Cochrane Database Syst Rev. PY 2012 IS 7 AR CD005059 DI 10.1002/14651858.CD005059.pub3 PG 86 WC Medicine, General & Internal SC General & Internal Medicine GA 972ME UT WOS:000306280400020 PM 22786494 ER PT J AU Kertesz, S Polli, D Holt, C Johnson-Roe, K Gordon, A Steward, J Borden, A Kim, T Stringfellow, E AF Kertesz, Stefan Polli, David Holt, Cheryl Johnson-Roe, Kay Gordon, Adam Steward, Jocelyn Borden, Allison Kim, Theresa Stringfellow, Erin TI Implications of Substance Abuse for Primary Care Quality of Homeless Patients SO SUBSTANCE ABUSE LA English DT Meeting Abstract C1 [Kertesz, Stefan] Birmingham VA Med Ctr, Birmingham, AL USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 0889-7077 J9 SUBST ABUS JI Subst. Abus. PY 2012 VL 33 IS 2 BP 220 EP 221 PG 2 WC Substance Abuse SC Substance Abuse GA 974UZ UT WOS:000306464200069 ER PT J AU Gordon, AJ Alford, DP AF Gordon, Adam J. Alford, Daniel P. TI Screening, Brief Intervention, and Referral to Treatment (SBIRT) Curricular Innovations: Addressing a Training Gap SO SUBSTANCE ABUSE LA English DT Editorial Material ID PRIMARY-CARE; ALCOHOL-PROBLEMS; EMERGENCY-DEPARTMENT; DRUG-USE; HEALTH; PHYSICIANS; MEDICINE; HOMELESS; BENEFIT; TIME C1 [Gordon, Adam J.] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. [Gordon, Adam J.] Univ Pittsburgh, Sch Med, Pittsburgh, PA USA. [Alford, Daniel P.] Boston Univ, Sch Med, Boston, MA 02118 USA. [Alford, Daniel P.] Boston Med Ctr, Boston, MA USA. RP Gordon, AJ (reprint author), VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. NR 34 TC 13 Z9 13 U1 2 U2 2 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 0889-7077 J9 SUBST ABUS JI Subst. Abus. PY 2012 VL 33 IS 3 SI SI BP 227 EP 230 DI 10.1080/08897077.2011.640156 PG 4 WC Substance Abuse SC Substance Abuse GA 974UT UT WOS:000306463600001 PM 22737999 ER PT J AU Childers, JW Broyles, LM Hanusa, BH Kraemer, KL Conigliaro, J Spagnoletti, C McNeil, M Gordon, AJ AF Childers, Julie W. Broyles, Lauren M. Hanusa, Barbara H. Kraemer, Kevin L. Conigliaro, Joseph Spagnoletti, Carla McNeil, Melissa Gordon, Adam J. TI Teaching the Teachers: Faculty Preparedness and Evaluation of a Retreat in Screening, Brief Intervention, and Referral to Treatment SO SUBSTANCE ABUSE LA English DT Article DE Alcohol-related disorders; continuing education; faculty; medical education; substance abuse ID ATTITUDES; DISORDERS; EDUCATION AB Effective clinical faculty are essential for disseminating substance abuse screening, brief intervention, and referral to treatment (SBIRT). The authors developed an 8-hour SBIRT training for internal medicine faculty preceptors. Trainers conducted SBIRT lectures and small-group communication practice sessions. The authors assessed participants' (n = 27) knowledge, skills, and attitudes using an enhanced Alcohol and Alcohol Problems Perceptions Questionnaire (AAPPQ). Participants self-assessed their changes in SBIRT competence and comfort. Faculty trainees did not feel competent in SBIRT, particularly in intervention and referral to treatment. AAPPQ subscale scores were highest in Role Legitimacy and Motivation and lowest in Role Adequacy and Satisfaction. After training, faculty members reported greater likelihood of performing and teaching SBIRT. In some topic areas, faculty attending an SBIRT training reported limited knowledge and competence for treating drinkers; however, their interest and motivation for doing so was high. Ongoing faculty and organizational development efforts may help close these gaps. C1 [Childers, Julie W.] Univ Pittsburgh, Sch Med, Dept Med, Div Gen Internal Med,Sect Palliat Care & Med Eth, Pittsburgh, PA 15213 USA. [Broyles, Lauren M.; Hanusa, Barbara H.; Gordon, Adam J.] VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA USA. [Broyles, Lauren M.; Hanusa, Barbara H.; Gordon, Adam J.] VA Pittsburgh Healthcare Syst, Mental Illness Res Educ & Clin Ctr, Pittsburgh, PA USA. [Kraemer, Kevin L.; McNeil, Melissa; Gordon, Adam J.] Univ Pittsburgh, Ctr Res Hlth Care, Pittsburgh, PA 15213 USA. [Conigliaro, Joseph] NYU, Dept Internal Med, Langone Med Ctr, New York, NY USA. RP Childers, JW (reprint author), Univ Pittsburgh, Sch Med, Dept Med, Div Gen Internal Med,Sect Palliat Care & Med Eth, Iroqouis Bldg,Suite 405, Pittsburgh, PA 15213 USA. EM childersjw2@upmc.edu FU SBIRT Substance Abuse and Mental Health Service Administration (SAMHSA); SBIRT Center for Substance Abuse Treatment (CSAT) [1TI020263-01]; Division of General Internal Medicine, University of Pittsburgh School of Medicine FX This work was partially funded by the SBIRT in Medical Residency Training Program (Substance Abuse and Mental Health Service Administration (SAMHSA) and the Center for Substance Abuse Treatment (CSAT), 1TI020263-01, Principal Investigator: Janice Pringle, PhD). Additional infrastructure support funding was provided by the Division of General Internal Medicine, University of Pittsburgh School of Medicine. NR 16 TC 3 Z9 3 U1 2 U2 5 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 0889-7077 EI 1547-0164 J9 SUBST ABUS JI Subst. Abus. PY 2012 VL 33 IS 3 SI SI BP 272 EP 277 DI 10.1080/08897077.2011.639686 PG 6 WC Substance Abuse SC Substance Abuse GA 974UT UT WOS:000306463600006 PM 22738004 ER PT J AU Satterfield, JM O'Sullivan, P Satre, DD Tsoh, JY Batki, SL Julian, K McCance-Katz, EF Wamsley, M AF Satterfield, Jason M. O'Sullivan, Patricia Satre, Derek D. Tsoh, Janice Y. Batki, Steven L. Julian, Kathy McCance-Katz, Elinore F. Wamsley, Maria TI Using Standardized Patients to Evaluate Screening, Brief Intervention, and Referral to Treatment (SBIRT) Knowledge and Skill Acquisition for Internal Medicine Residents SO SUBSTANCE ABUSE LA English DT Article DE Graduate medical education; SBIRT; standardized patients; substance use disorders AB Comprehensive clinical competency curricula for hazardous drinking and substance use disorders (SUDs) exists for medical students, residents, and practicing health care providers. Evaluations of these curricula typically focus on learner attitudes and knowledge, although changes in clinical skills are of greater interest and utility. The authors present a pre-post clinical skill evaluation of a 10-hour screening, brief intervention, and referral to treatment (SBIRT) curriculum for hazardous drinking and SUDs for primary care internal medicine residents using standardized patient examinations to better determine the impact of SBIRT training on clinical practice. Residents had large improvements in history taking, substance use screening skills, SUD assessment and diagnostic skills, and in SBIRT knowledge, including documentation, systems, and diversity issues. Residents made moderate improvements in brief intervention skills. Future SBIRT curricular evaluations would ideally include a controlled comparison with larger samples from multiple institutions. C1 [Satterfield, Jason M.; O'Sullivan, Patricia; Julian, Kathy; Wamsley, Maria] Univ Calif San Francisco, Div Gen Internal Med, San Francisco, CA 94143 USA. [Satre, Derek D.; Tsoh, Janice Y.; Batki, Steven L.; McCance-Katz, Elinore F.] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94143 USA. [Satre, Derek D.] Kaiser Permanente Div Res, San Francisco, CA USA. [Batki, Steven L.] San Francisco Vet Adm Med Ctr, San Francisco, CA USA. RP Satterfield, JM (reprint author), Univ Calif San Francisco, Div Gen Internal Med, 1545 Divisadero St,Box 0320, San Francisco, CA 94143 USA. EM Jsatter@medicine.ucsf.edu NR 8 TC 12 Z9 12 U1 0 U2 2 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 0889-7077 EI 1547-0164 J9 SUBST ABUS JI Subst. Abus. PY 2012 VL 33 IS 3 SI SI BP 303 EP 307 DI 10.1080/08897077.2011.640103 PG 5 WC Substance Abuse SC Substance Abuse GA 974UT UT WOS:000306463600012 PM 22738010 ER PT J AU Arnstein, PM AF Arnstein, Paul M. TI Evolution of Topical NSAIDs in the Guidelines for Treatment of Osteoarthritis in Elderly Patients SO DRUGS & AGING LA English DT Article ID NONSTEROIDAL ANTIINFLAMMATORY DRUGS; QUALITY-OF-LIFE; OLDER-ADULTS; KNEE OSTEOARTHRITIS; GASTROINTESTINAL TOXICITY; CARDIOVASCULAR RISKS; BLOOD-PRESSURE; MANAGEMENT; HIP; PREVENTION AB Increasing age is the primary predictor of osteoarthritis, the most prevalent painful condition in the US. Because there are no disease-modifying therapies for osteoarthritis, relief of symptoms and maintenance of quality of life through improving joint function become the focus of management. Although highly effective for pain relief, oral nonsteroidal anti-inflammatory drugs (NSAIDs) are associated with systemic adverse reactions that are sometimes treatment limiting, especially for older patients. Thus, osteoarthritis management in elderly populations is shifting away from traditional NSAIDs to therapies that provide comparable pain relief with improved safety. Since the approval by the US Food and Drug Administration of the use of topical NSAIDs to manage osteoarthritis pain, current treatment guidelines put forth by several professional societies have begun to recommend topical NSAIDs as an alternative therapy and, most recently, as first-line therapy for osteoarthritis management in the elderly. This review provides an overview of the various treatment guidelines that are available to assist prescribers in making safe and effective decisions in the treatment of osteoarthritis in this high-risk patient population. C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Arnstein, PM (reprint author), Massachusetts Gen Hosp, GRB-1034,55 Fruit St, Boston, MA 02114 USA. EM pmarnstein@partner.org FU Mallinckrodt Inc., a Covidien company, Hazelwood, MO, USA FX Technical editorial and medical writing assistance for the development of this manuscript was provided by Lauren Burawski, MA, Synchrony Medical, LLC, West Chester, PA, USA. Funding for this support was provided by Mallinckrodt Inc., a Covidien company, Hazelwood, MO, USA. NR 70 TC 10 Z9 11 U1 1 U2 2 PU ADIS INT LTD PI AUCKLAND PA 41 CENTORIAN DR, PRIVATE BAG 65901, MAIRANGI BAY, AUCKLAND 1311, NEW ZEALAND SN 1170-229X J9 DRUG AGING JI Drugs Aging PY 2012 VL 29 IS 7 BP 523 EP 531 PG 9 WC Geriatrics & Gerontology; Pharmacology & Pharmacy SC Geriatrics & Gerontology; Pharmacology & Pharmacy GA 974OG UT WOS:000306445200001 PM 22559274 ER PT J AU Norton, BA Thomas, R Lomax, KG Dudley-Brown, S AF Norton, Beth-Ann Thomas, Rosemarie Lomax, Kathleen G. Dudley-Brown, Sharon TI Patient perspectives on the impact of Crohn's disease: results from group interviews SO PATIENT PREFERENCE AND ADHERENCE LA English DT Article DE Crohn's disease; patient perspective; quality of life ID INFLAMMATORY-BOWEL-DISEASE; ULCERATIVE-COLITIS; PATIENTS PREFERENCES; NURSE-PRACTITIONERS; CERTOLIZUMAB PEGOL; RANDOMIZED-TRIAL; TOP-DOWN; MANAGEMENT; INFLIXIMAB; QUALITY AB Aim: To understand the impact of Crohn's disease (CD) on various aspects of daily life from the perspective of patients living with CD. Awareness of the disease and biologic therapies, patient satisfaction and adherence, and physician (provider) relationships were also assessed. Background: CD is a chronic, inflammatory, autoimmune disorder of the gastrointestinal tract that substantially impacts patients' physical and emotional well-being. For patients eligible for biologic therapy, anti-tumor necrosis factor agents represent an important addition to the available therapies for CD. Methods: The study sample included biologic-naive and biologic-experienced patients who had self-reported moderate to severe CD, were under the care of a specialist, and agreed to film a video diary and participate in a focus group. Data from the videos and group interviews were collected from May to June of 2009 and summarized qualitatively by grouping similar answers and quotations. Results: Of the 44 participants who submitted video diaries, 23 were biologic-experienced and 21 were biologic-naive. Participants stated that CD caused fear and embarrassment, that they were reluctant to share the full impact of CD with family and providers, and that they relied on their provider for treatment decisions. Many participants accepted a new state of normalcy if their current medication helped their most bothersome symptoms without providing sustained remission. Participants receiving biologic therapy generally were more informed, more-satisfied, and more likely to adhere to treatment regimens. Conclusion: Participants' responses suggest a need for more patient education and more collaborative relationships between patients and providers (physicians) regarding treatment decisions. C1 [Norton, Beth-Ann] Massachusetts Gen Hosp, Boston, MA 01224 USA. [Thomas, Rosemarie; Lomax, Kathleen G.] Abbott Labs, Abbott Pk, IL USA. [Dudley-Brown, Sharon] Johns Hopkins Univ, Sch Med, Baltimore, MD USA. [Dudley-Brown, Sharon] Johns Hopkins Univ, Sch Nursing, Baltimore, MD USA. RP Norton, BA (reprint author), Massachusetts Gen Hosp, 165 Cambridge St,9th Floor, Boston, MA 01224 USA. EM beth-ann.norton@mssm.edu FU Abbott Laboratories; Abbott FX Medical writing services were provided by Eileen M Burkhart-Hartman, PhD, of Abbott Laboratories; Cathryn M Carter, MS, of Arbor Communications; and Elaine Hanna, MA. This support was funded by Abbott Laboratories. The authors would like to thank the patients for their participation in this research.; Beth-Ann Norton is a consultant for UCB and Abbott Laboratories. Rosemarie Thomas is an employee of Abbott Laboratories and owns stock. Sharon Dudley-Brown is a consultant for Shire, UCB, and Salix Pharmaceuticals. Kathleen G Lomax is a former employee of Abbott Laboratories. Abbott was the financial sponsor of this study. This research was conducted by M/A/R/C Research under contract with Abbott. NR 48 TC 4 Z9 5 U1 0 U2 13 PU DOVE MEDICAL PRESS LTD PI ALBANY PA PO BOX 300-008, ALBANY, AUCKLAND 0752, NEW ZEALAND SN 1177-889X J9 PATIENT PREFER ADHER JI Patient Prefer. Adherence PY 2012 VL 6 BP 509 EP 520 DI 10.2147/PPA.S32690 PG 12 WC Medicine, General & Internal SC General & Internal Medicine GA 974CI UT WOS:000306407000001 PM 22879737 ER PT J AU Alcantara, D Guo, YY Yuan, HS Goergen, CJ Chen, HH Cho, HS Sosnovik, DE Josephson, L AF Alcantara, David Guo, Yanyan Yuan, Hushan Goergen, Craig J. Chen, Howard H. Cho, Hoonsung Sosnovik, David E. Josephson, Lee TI Fluorochrome-Functionalized Magnetic Nanoparticles for High-Sensitivity Monitoring of the Polymerase Chain Reaction by Magnetic Resonance SO ANGEWANDTE CHEMIE-INTERNATIONAL EDITION LA English DT Article DE fluorescence; imaging agents; magnetic nanoparticles; magnetic resonance imaging; polymerase chain reaction ID THIAZOLE ORANGE; MOLECULAR-INTERACTIONS; DNA; NMR; PURIFICATION; FERUMOXYTOL; NANOSENSORS; EXTRACTION; KINETICS; BINDING C1 [Alcantara, David; Guo, Yanyan; Yuan, Hushan; Cho, Hoonsung; Sosnovik, David E.; Josephson, Lee] Massachusetts Gen Hosp, Ctr Translat Nucl Med & Mol Imaging, Charlestown, MA 02129 USA. [Alcantara, David] Univ Zaragoza, Inst Nanociencia Aragon, Zaragoza 50018, Spain. [Goergen, Craig J.; Chen, Howard H.; Sosnovik, David E.; Josephson, Lee] Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. RP Josephson, L (reprint author), Massachusetts Gen Hosp, Ctr Translat Nucl Med & Mol Imaging, 149 13th St, Charlestown, MA 02129 USA. EM ljosephson@mgh.harvard.edu RI Alcantara, David /A-3357-2014; OI Goergen, Craig/0000-0001-8883-7953 FU NIH [R01 EB009691, R01 EB011996, R01 HL093038]; Marie Curie Fellowship (IOF, MRI Nanobiosensor) FX This work was funded by NIH grants R01 EB009691 and R01 EB011996 to L.J. and R01 HL093038 (D.E.S.). D.A. was a recipient of a Marie Curie Fellowship (IOF, MRI Nanobiosensor). NR 29 TC 16 Z9 16 U1 2 U2 24 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA BOSCHSTRASSE 12, D-69469 WEINHEIM, GERMANY SN 1433-7851 J9 ANGEW CHEM INT EDIT JI Angew. Chem.-Int. Edit. PY 2012 VL 51 IS 28 BP 6904 EP 6907 DI 10.1002/anie.201201661 PG 4 WC Chemistry, Multidisciplinary SC Chemistry GA 968NY UT WOS:000305990800016 PM 22684680 ER PT J AU Amariglio, RE Frishe, K Olson, LE Wadsworth, LP Lorius, N Sperling, RA Rentz, DM AF Amariglio, Rebecca E. Frishe, Katherine Olson, Lauren E. Wadsworth, Lauren P. Lorius, Natacha Sperling, Reisa A. Rentz, Dorene M. TI Validation of the Face Name Associative Memory Exam in cognitively normal older individuals SO JOURNAL OF CLINICAL AND EXPERIMENTAL NEUROPSYCHOLOGY LA English DT Article DE Preclinical Alzheimer's disease; Aging; Neuropsychology; Instrument validation ID PRECLINICAL ALZHEIMERS-DISEASE; AMYLOID DEPOSITION; NEUROPSYCHOLOGICAL TESTS; IMPAIRMENT; DEMENTIA; ACTIVATION; PERFORMANCE; DEFICITS; DECLINE; FMRI AB The recently developed Face Name Associative Memory Exam (FNAME), a challenging paired associative learning task, shows promise in detecting the subtle cognitive changes characteristic of preclinical Alzheimer's disease. In this study, we evaluated the validity and reliability of the FNAME in 210 cognitively normal older individuals (58-90 years of age). Construct validity of the measure was assessed by principal components analysis, which revealed two independent factors. Correlations between the FNAME subtests and another episodic memory test were significant. The results indicated strong test-retest reliability in a subsample (n = 41). Normative data stratified by age were also generated. C1 [Amariglio, Rebecca E.; Frishe, Katherine; Olson, Lauren E.; Lorius, Natacha; Sperling, Reisa A.; Rentz, Dorene M.] Brigham & Womens Hosp, Ctr Alzheimer Res & Treatment, Dept Neurol, Boston, MA 02115 USA. [Amariglio, Rebecca E.; Olson, Lauren E.; Wadsworth, Lauren P.; Lorius, Natacha; Sperling, Reisa A.; Rentz, Dorene M.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Amariglio, Rebecca E.; Sperling, Reisa A.; Rentz, Dorene M.] Harvard Univ, Sch Med, Boston, MA USA. RP Amariglio, RE (reprint author), Div Cognit & Behav Neurol, 221 Longwood Ave, Boston, MA 02115 USA. EM ramariglio@partners.org FU Alzheimer Association [IIRG-08-90934]; Charles H. Farnsworth Trust; National Institute on Aging [P01-AG036694-01, P50-AG00513421, R01-AG027435, R01-AG027435-S1] FX This work was supported by Alzheimer Association Grants IIRG-08-90934 (D. R.), by the Charles H. Farnsworth Trust (D. R.), and by National Institute on Aging Grants P01-AG036694-01 (R. S.), P50-AG00513421 (R. S.), R01-AG027435 (R. S.), and R01-AG027435-S1 (R. S). The authors wish to thank M. Frey for helping to collect FNAME data, the investigators and staff of the Massachusetts Alzheimer's Disease Research Center, and the individual research participants. NR 34 TC 14 Z9 14 U1 1 U2 12 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1380-3395 J9 J CLIN EXP NEUROPSYC JI J. Clin. Exp. Neuropsychol. PY 2012 VL 34 IS 6 BP 580 EP 587 DI 10.1080/13803395.2012.666230 PG 8 WC Psychology, Clinical; Clinical Neurology; Psychology SC Psychology; Neurosciences & Neurology GA 970YM UT WOS:000306168400003 PM 22765048 ER PT J AU Campos, SM Berlin, S Matulonis, UA Muto, MG Pereira, L Mosquera, MM Horowitz, N AF Campos, Susana M. Berlin, Suzanne Matulonis, Ursula A. Muto, Michael G. Pereira, Lauren Mosquera, Merily M. Horowitz, Neil TI Young Women Diagnosed with Early-Stage Ovarian Cancer or Borderline Malignancy of the Ovary: A Focus on Fertility and Sexual Function SO JOURNAL OF PSYCHOSOCIAL ONCOLOGY LA English DT Article DE ovarian cancer; borderline malignancy of the ovary; fertility options; sexual function; survival ID GERM-CELL TUMORS; SPARING SURGERY; AGE; PRESERVATION; CARCINOMA; MANAGEMENT; HEALTH AB Malignant ovarian neoplasms represent the leading cause of death in gynecological malignancies. Although the majority of ovarian neoplasms occur in women of advanced years, ovarian neoplasms can occur in women of the reproductive age group. Preservation of fertility balanced with treatment of disease is the goal of young patients diagnosed with ovarian neoplasms. A new discipline termed "oncofertility" has emerged; however, several informational gaps exist. Concern has centered on the safety of conservative treatment, the uncertain efficacy of fertility options, the detrimental effects of chemotherapy to remaining reproductive organs, and the timing and execution of fertility workup relative to disease requiring treatment. This study involved an evaluation of young premenopausal women who underwent fertility-sparing surgery for an ovarian neoplasm. Given the rarity of this disease in premenopausal women the objective was to assess the feasibility of this study as defined by the completion rate of the survey. The aim was to broaden our knowledge of patient needs to partner with our survivorship clinic thereby ensuring that patients may facilitate their options. Patients were asked to complete a questionnaire titled Ovarian Cancer or Borderline Malignancy of the Ovary: Fertility Sparing Survey and a previously published instrument termed The Sexual Activity Questionnaire, a 21-item scale that assessed the impact of treatment on sexual functioning. All participants completed the survey illustrating the feasibility of the study. The study revealed that the majority of patients (91%) discussed fertility options with their clinicians, yet only 16% engaged in measures to preserve fertility. Patient's sexual interest and activity was maintained in this cohort of patients. This underscores the importance of continued studies in this unique population to ensure optimal fertility counseling and to better delineate the sexual well-being of young women diagnosed with ovarian neoplasms. C1 [Campos, Susana M.; Berlin, Suzanne; Matulonis, Ursula A.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Gynecol Oncol, Boston, MA 02115 USA. [Muto, Michael G.; Horowitz, Neil] Brigham & Womens Hosp, Div Gynecol Oncol, Boston, MA 02115 USA. RP Campos, SM (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Gynecol Oncol, 450 Brookline Ave, Boston, MA 02115 USA. EM scampos@partners.org NR 36 TC 5 Z9 5 U1 1 U2 8 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 0734-7332 J9 J PSYCHOSOC ONCOL JI J. Psychosoc. Oncol. PY 2012 VL 30 IS 4 BP 387 EP 401 DI 10.1080/07347332.2012.684854 PG 15 WC Psychology, Social SC Psychology GA 970DY UT WOS:000306109500001 PM 22747104 ER PT J AU Bogdanov, AA Metelev, V Zhang, SR Kumar, ATN AF Bogdanov, Alexei A., Jr. Metelev, Valeriy Zhang, Surong Kumar, Anand T. N. TI Sensing of transcription factor binding via cyanine dye pair fluorescence lifetime changes SO MOLECULAR BIOSYSTEMS LA English DT Article ID NF-KAPPA-B; RESONANCE ENERGY-TRANSFER; SURFACE-PLASMON RESONANCE; DONOR-ACCEPTOR PAIR; IN-VIVO; INTRAMOLECULAR DIMERS; CRYSTAL-STRUCTURE; DNA INTERACTIONS; TURBID MEDIA; TOMOGRAPHY AB We designed and synthesized sensors for imaging transcription factor-DNA interactions using a complementary pair of 21-base pair long oligonucleotides (ODNs) carrying two internucleoside phosphate-linked cyanine fluorophores that can either engage in Forster's resonance energy transfer (FRET) with fluorescence emission or assemble into a ground state quenched dimer with short fluorescence lifetimes (FL). Cyanine fluorophores were linked to ODNs within the NF-kappa B binding site. These sensors were tested in the presence of recombinant p50 and p65 NF-kappa B proteins or constitutively NF-kappa B activating HeLa cell lysates. By using a coherent light excitation source we followed changes in fluorescence lifetime of the donor (Cy5.5) at the donor's excitation and emission light wavelengths, as well as the acceptor (800CW or Cy7 cyanine fluorophores) in FRET mode. We observed increases in the donor lifetime in both emitting (0.08 0.15 ns) and non-emitting quenched (0.21 ns) sensors in response to protein binding. The measurements of lifetimes in FRET mode in quenched pair-carrying ODN duplex sensors showed significant differences in FL of the acceptor cyanine fluorophore between NF-kappa B-containing and NF-kappa B-free samples but not in control sensors with ODN sequences that have decreased binding affinity to NF-kappa B. We anticipate that the observed effects will be instrumental for developing sensors enabling non-invasive imaging in cells that undergo activation of NF-kappa B. C1 [Bogdanov, Alexei A., Jr.; Metelev, Valeriy; Zhang, Surong] Univ Massachusetts, Sch Med, Dept Radiol, Lab Mol Imaging Probes, Worcester, MA 01655 USA. [Metelev, Valeriy] Moscow MV Lomonosov State Univ, Dept Chem, Moscow, Russia. [Kumar, Anand T. N.] Massachusetts Gen Hosp, A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. RP Bogdanov, AA (reprint author), Univ Massachusetts, Sch Med, Dept Radiol, Lab Mol Imaging Probes, S6-434,55 Lake Ave N, Worcester, MA 01655 USA. EM Alexei.Bogdanov@umassmed.edu RI Metelev, Valeri/I-3238-2012 FU National Cancer Institute IMAT grant [R33CA134385, R01EB015325, R01AG026240] FX This work was supported in part by the National Cancer Institute IMAT grant R33CA134385 to A.B., R01EB015325 (to A.T.N.K.) and R01AG026240. The authors are grateful to Dr David Tabatadze (ZATA Pharmaceuticals) for his work on ODN synthesis. NR 34 TC 5 Z9 5 U1 2 U2 15 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 1742-206X J9 MOL BIOSYST JI Mol. Biosyst. PY 2012 VL 8 IS 8 BP 2166 EP 2173 DI 10.1039/c2mb25057h PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 968GK UT WOS:000305965100015 PM 22710322 ER PT J AU Biederman, J Spencer, TJ Petty, C Hyder, LL O'Connor, KB Surman, CBH Faraone, SV AF Biederman, Joseph Spencer, Thomas J. Petty, Carter Hyder, Laran L. O'Connor, Katherine B. Surman, Craig B. H. Faraone, Stephen V. TI Longitudinal course of deficient emotional self-regulation CBCL profile in youth with ADHD: prospective controlled study SO NEUROPSYCHIATRIC DISEASE AND TREATMENT LA English DT Article DE attention-deficit/hyperactivity disorder; emotion; regulation; longitudinal; youth ID CHILD-BEHAVIOR CHECKLIST; FAMILY RISK ANALYSIS; BIPOLAR DISORDER; HYPERACTIVITY DISORDER; SOCIAL-ADJUSTMENT; ATTENTION; ADOLESCENTS AB Background: While symptoms of deficient emotional self-regulation (DESR) have been long associated with attention-deficit/hyperactivity disorder (ADHD), there has been limited investigation of this aspect of the clinical picture of the disorder. The main aim of this study was to examine the predictive utility of DESR in moderating the course of ADHD children into adolescence. Methods: Subjects comprised 177 children with and 204 children without ADHD followed for an average of 4 years (aged 6-18 years at baseline, 54% male). Subjects were assessed with structured diagnostic interviews and measures of psychosocial functioning. DESR was defined by the presence (n = 79) or absence (n = 98) of Child Behavior Checklist (CBCL)-DESR profile (score >= 180 < 210 total of Attention, Aggression, and Anxious/Depressed subscales) at the baseline assessment. Results: Of subjects with DESR at baseline, 57% had DESR at follow-up. Persistent ADHD was significantly associated with DESR at follow-up (chi(2)((1)) = 15.37, P < 0.001). At follow-up, ADHD + DESR subjects had significantly more comorbidities (z = 2.55, P = 0.01), a higher prevalence of oppositional defiant disorder (z = 3.01, P = 0.003), and more impaired CBCL social problems t-score (t((227)) = 2.41, P = 0.02) versus ADHD subjects. Conclusion: This work suggests that a positive CBCL-DESR profile predicts subsequent psychopathology and functional impairments in children with ADHD suggesting that it has the potential to help identify children with ADHD at high risk for compromised outcomes. C1 [Biederman, Joseph; Spencer, Thomas J.; Petty, Carter; Hyder, Laran L.; O'Connor, Katherine B.; Surman, Craig B. H.] Massachusetts Gen Hosp, Clin & Res Program Pediat Psychopharmacol & Adult, Pediat Psychopharmacol Unit, Yawkey Ctr Outpatient Care, Boston, MA 02114 USA. [Biederman, Joseph; Spencer, Thomas J.; Surman, Craig B. H.] Harvard Univ, Sch Med, Dept Psychiat, Cambridge, MA 02138 USA. [Faraone, Stephen V.] SUNY Upstate Med Univ, Dept Psychiat & Neurosci, Syracuse, NY USA. [Faraone, Stephen V.] SUNY Upstate Med Univ, Dept Physiol, Syracuse, NY USA. RP Biederman, J (reprint author), Massachusetts Gen Hosp, Clin Program Pediat Psychopharmacol & Adult ADHD, 55 Fruit St,YAW6A, Boston, MA 02114 USA. EM jbiederman@partners.org FU National Institutes of Health [R01 HD36317, R01 MH50657]; Shire Pharmaceuticals; Elminda; Janssen; McNeil; Shire; MGH Psychiatry Academy; Fundacion Areces (Spain); Medice Pharmaceuticals (Germany); Spanish Child Psychiatry Association; Abbott; Alza; AstraZeneca; Boston University; Bristol Myers Squibb; Celltech; Cephalon; Eli Lilly and Co; Esai; Forest; Glaxo; Gliatech; Hastings Center; Merck; MMC Pediatric; NARSAD; NIDA; New River; NICHD; NIMH; Novartis; Noven; Neurosearch; Organon; Otsuka; Pfizer; Pharmacia; Phase V Communications; Physicians Academy; Prechter Foundation; Quantia Communications; Reed Exhibitions; Stanley Foundation; UCB Pharma Inc; Veritas; Wyeth; Shire Laboratories Inc; Eli Lilly and Company; Glaxo-Smith Kline; McNeil Pharmaceutical; Novartis Pharmaceuticals; MGH Corporate Sponsored Research and Licensing; Hilda and Preston Davis Foundation; National Institutes of Health; Takeda; Janssen-Ortho; Alcobra FX JB is currently receiving research support from the following sources: Elminda, Janssen, McNeil, and Shire. In 2011, JB gave a single unpaid talk for Juste Pharmaceutical Spain, received honoraria from the MGH Psychiatry Academy for a tuition-funded continuing medical education course, and received an honorarium for presenting at an international scientific conference on ADHD. He also received an honorarium from Cambridge University Press for a chapter publication. JB received departmental royalties from a copyrighted rating scale used for ADHD diagnoses, paid by Eli Lilly, Shire and AstraZeneca; these royalties are paid to the Department of Psychiatry at MGH. In 2010, JB received a speaker's fee from a single talk given at Fundacion Dr Manuel Camelo AC in Monterrey Mexico. JB provided single consultations for Shionogi Pharma Inc and Cipher Pharmaceuticals Inc; the honoraria for these consultations were paid to the Department of Psychiatry at the MGH. JB received honoraria from the MGH Psychiatry Academy for a tuition-funded continuing medical education course. In 2009, JB received a speaker's fee from the following sources: Fundacion Areces (Spain), Medice Pharmaceuticals (Germany), and the Spanish Child Psychiatry Association. In previous years, JB has received research support, consultation fees, or speaker's fees for/from the following additional sources: Abbott, Alza, AstraZeneca, Boston University, Bristol Myers Squibb, Celltech, Cephalon, Eli Lilly and Co, Esai, Forest, Glaxo, Gliatech, Hastings Center, Janssen, McNeil, Merck, MMC Pediatric, NARSAD, NIDA, New River, NICHD, NIMH, Novartis, Noven, Neurosearch, Organon, Otsuka, Pfizer, Pharmacia, Phase V Communications, Physicians Academy, The Prechter Foundation, Quantia Communications, Reed Exhibitions, Shire, The Stanley Foundation, UCB Pharma Inc, Veritas, and Wyeth.; TS has received research support from the following sources: Shire Laboratories Inc, Cephalon, Eli Lilly and Company, Glaxo-Smith Kline, Janssen, McNeil Pharmaceutical, Novartis Pharmaceuticals, Pfizer, and NIMH. TS has been a speaker or on a speaker's bureau for the following pharmaceutical companies: Shire Laboratories Inc, Eli Lilly and Company, Glaxo-Smith Kline, Janssen, McNeil Pharmaceutical, and Novartis Pharmaceuticals. TS has been an advisor or on an advisory board for the following pharmaceutical companies: Shire Laboratories Inc, Cephalon, Eli Lilly and Company, Glaxo-Smith Kline, Janssen, McNeil Pharmaceutical, Novartis Pharmaceuticals, and Pfizer. TS receives research support from royalties and licensing fees on copyrighted ADHD scales through MGH Corporate Sponsored Research and Licensing. TS has a US patent application pending (Provisional Number 61/233,686), through MGH corporate licensing, on a method to prevent stimulant abuse.; CBHS has received research support from Abbott, Alza, Cephalon, Eli Lilly, the Hilda and Preston Davis Foundation, McNeil, Merck, New River, National Institutes of Health, Organon, Pfizer, Shire, and Takeda; has received support from Janssen-Ortho, McNeil, Novartis, and Shire for speaking and other educational activities; and has been a consultant/advisor for McNeil, Shire, Somaxon, and Takeda. CBHS has also received honoraria from Reed Medical Education (a logistics collaborator for the MGH Psychiatry Academy). Commercial entities supporting the MGH Psychiatry Academy are listed on the academy's web site, http://www.mghcme.org.; In the past year, SVF received consulting income and research support from Shire and Alcobra and research support from the National Institutes of Health. In previous years, he received consulting fees or was on advisory boards or participated in continuing medical education programs sponsored by: Shire, McNeil, Janssen, Novartis, Pfizer and Eli Lilly. SVF receives royalties from books published by Guilford Press (Straight Talk about Your Child's Mental Health) and Oxford University Press (Schizophrenia: The Facts).; CP, LH, and KOC report no conflict of interest in this work. This manuscript was supported in part by grants to JB from the National Institutes of Health (R01 HD36317, R01 MH50657) and to TS from Shire Pharmaceuticals. NR 28 TC 19 Z9 19 U1 2 U2 24 PU DOVE MEDICAL PRESS LTD PI ALBANY PA PO BOX 300-008, ALBANY, AUCKLAND 0752, NEW ZEALAND SN 1176-6328 J9 NEUROPSYCH DIS TREAT JI Neuropsychiatr. Dis. Treat. PY 2012 VL 8 BP 267 EP 276 DI 10.2147/NDT.S29670 PG 10 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 973DZ UT WOS:000306336900001 PM 22848182 ER PT J AU Binagwaho, A Fuller, A Kerry, V Dougherty, S Agbonyitor, M Wagner, C Nzayizera, R Farmer, P AF Binagwaho, Agnes Fuller, Arlan Kerry, Vanessa Dougherty, Sarah Agbonyitor, Mawuena Wagner, Claire Nzayizera, Rodrigue Farmer, Paul TI Adolescents and the right to health: Eliminating age-related barriers to HIV/AIDS services in Rwanda SO AIDS CARE-PSYCHOLOGICAL AND SOCIO-MEDICAL ASPECTS OF AIDS/HIV LA English DT Article DE HIV/AIDS; adolescents; age of majority; Rwanda; barriers to care AB Under international, regional, and domestic law, adolescents are entitled to measures ensuring the highest attainable standard of health. For HIV/AIDS, this is essential as adolescents lack many social and economic protections and are disproportionately vulnerable to the effects of the disease. In many countries, legal protections do not always ensure access to health care for adolescents, including for HIV/AIDS prevention, treatment, and care. Using Rwanda as an example, this article identifies gaps, policy barriers, and inconsistencies in legal protection that can create age-related barriers to HIV/AIDS services and care. One of the most pressing challenges is defining an age of majority for access to prevention measures, such as condoms, testing and treatment, and social support. Occasionally drawing on examples of existing and proposed laws in other African countries, Rwanda and other countries may strengthen their commitment to adolescents' rights and eliminate barriers to prevention, family planning, testing and disclosure, treatment, and support. Among the improvements, Rwanda and other countries must align its age of consent with the actual behavior of adolescents and ensure privacy to adolescents regarding family planning, HIV testing, disclosure, care, and treatment. C1 [Kerry, Vanessa] Massachusetts Gen Hosp, Ctr Global Hlth, Boston, MA 02114 USA. [Binagwaho, Agnes] Minist Hlth, Kigali, Rwanda. [Fuller, Arlan; Dougherty, Sarah] Harvard Univ, Sch Publ Hlth, FXB Ctr, Boston, MA 02115 USA. [Binagwaho, Agnes; Kerry, Vanessa; Agbonyitor, Mawuena; Wagner, Claire; Farmer, Paul] Harvard Univ, Sch Med, Dept Global Hlth & Social Med, Boston, MA USA. [Nzayizera, Rodrigue] Univ Rwanda, Butare, Rwanda. [Farmer, Paul] Brigham & Womens Hosp, Div Global Hlth Equ, Boston, MA 02115 USA. RP Kerry, V (reprint author), Massachusetts Gen Hosp, Ctr Global Hlth, Boston, MA 02114 USA. EM vkerry@partners.org NR 36 TC 15 Z9 15 U1 1 U2 7 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 0954-0121 J9 AIDS CARE JI Aids Care-Psychol. Socio-Med. Asp. Aids-Hiv PY 2012 VL 24 IS 7 BP 936 EP 942 DI 10.1080/09540121.2011.648159 PG 7 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychology, Multidisciplinary; Respiratory System; Social Sciences, Biomedical SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychology; Respiratory System; Biomedical Social Sciences GA 968JB UT WOS:000305973900016 PM 22292484 ER PT J AU Yang, KS Budin, G Reiner, T Vinegoni, C Weissleder, R AF Yang, Katherine S. Budin, Ghyslain Reiner, Thomas Vinegoni, Claudio Weissleder, Ralph TI Bioorthogonal Imaging of Aurora Kinase A in Live Cells SO ANGEWANDTE CHEMIE-INTERNATIONAL EDITION LA English DT Article DE aurora kinase; cancer; cell cycle; cycloaddition; live cell imaging ID LIVING CELLS; CANCER; INHIBITORS; MLN8054; PROBES; POLES C1 [Yang, Katherine S.; Budin, Ghyslain; Reiner, Thomas; Vinegoni, Claudio; Weissleder, Ralph] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. [Weissleder, Ralph] Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Weissleder, R (reprint author), Massachusetts Gen Hosp, Ctr Syst Biol, 185 Cambridge St, Boston, MA 02114 USA. EM rweissleder@mgh.harvard.edu OI Reiner, Thomas/0000-0002-7819-5480 FU National Institutes of Health (NIH) [RO1EB010011, P50CA086355, T32-CA079443]; German Academy of Sciences Leopoldina [LPDS 2009-24] FX This work was supported by the National Institutes of Health (NIH) grant number RO1EB010011 and P50CA086355, K.Y. was supported by an NIH grant T32-CA079443 and T.R. was supported by a grant from the German Academy of Sciences Leopoldina (LPDS 2009-24). We thank Prof. Peter Sorger and Dr. Robert Yang for assistance with cellWoRx and ImageRail and Paolo Fumene Feruglio for assistance with image processing. We also thank Dr. Jonathan Carlson, Dr. Greg Thurber, and Dr. Carlos Tassa for helpful input and discussions about the manuscript. NR 21 TC 38 Z9 38 U1 3 U2 33 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA BOSCHSTRASSE 12, D-69469 WEINHEIM, GERMANY SN 1433-7851 J9 ANGEW CHEM INT EDIT JI Angew. Chem.-Int. Edit. PY 2012 VL 51 IS 27 BP 6598 EP 6603 DI 10.1002/anie.201200994 PG 6 WC Chemistry, Multidisciplinary SC Chemistry GA 968NE UT WOS:000305987900007 PM 22644700 ER PT J AU Ke, YG Bellot, G Voigt, NV Fradkov, E Shih, WM AF Ke, Yonggang Bellot, Gaetan Voigt, Niels V. Fradkov, Elena Shih, William M. TI Two design strategies for enhancement of multilayer-DNA-origami folding: underwinding for specific intercalator rescue and staple-break positioning SO CHEMICAL SCIENCE LA English DT Article ID NANOSCALE SHAPES; LATTICES; NANOTECHNOLOGY; TRANSFECTION; KINETICS; COMPLEX; CELLS AB Single-layer DNA origami is an efficient method for programmable self-assembly of nanostructures approximating almost any desired two-dimensional shape from similar to 5 MDa of DNA building material. In this method, a 7 kilobase single "scaffold" strand is assembled with hundreds of oligodeoxyribonucleotide "staple" strands to form a parallel array of double helices. Multiple layers of such DNA sheets also can be designed to assemble into a stack, enabling the construction of solid three-dimensional shapes with considerably greater mechanical rigidity than two-dimensional shapes; however, the folding yield often is much lower and the required folding times are much longer. Here we introduce two strategies for designing multi-layer DNA origami that demonstrate potential for boosting assembly yield: (1) individual base pairs can be inserted between crossovers, allowing for greater bowing of helices at positions away from crossovers and therefore reduced electrostatic repulsion. At the same time, this underwinding of double helices increases a destabilizing torsional strain energy but then also increases affinity for intercalators, and binding of such intercalators can relieve this stress. We also have exploited this enhanced affinity for intercalators to PEGylate the surface of the nanostructures in a noncovalent fashion using PEG-tris-acridine. (2) Positioning of staple-strand breaks in the DNA origami such that each staple strand includes a 14 nucleotide (nt) continuous segment that binds to a complementary 14 nt continuous segment of the scaffold can greatly improve folding yields. C1 [Ke, Yonggang; Bellot, Gaetan; Fradkov, Elena; Shih, William M.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [Ke, Yonggang; Bellot, Gaetan; Fradkov, Elena; Shih, William M.] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. [Ke, Yonggang; Bellot, Gaetan; Fradkov, Elena; Shih, William M.] Wyss Inst Biol Inspired Engn Harvard, Cambridge, MA 02138 USA. [Voigt, Niels V.] Aarhus Univ, Danish Natl Res Fdn, Ctr DNA Nanotechnol, Interdisciplinary Nanosci Ctr INANO, DK-8000 Aarhus, Denmark. [Voigt, Niels V.] Aarhus Univ, Dept Chem, DK-8000 Aarhus, Denmark. RP Shih, WM (reprint author), Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. EM William_Shih@dfci.harvard.edu FU NIH HHS [DP2 OD004641] NR 24 TC 32 Z9 32 U1 6 U2 52 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 2041-6520 J9 CHEM SCI JI Chem. Sci. PY 2012 VL 3 IS 8 BP 2587 EP 2597 DI 10.1039/c2sc20446k PG 11 WC Chemistry, Multidisciplinary SC Chemistry GA 967IO UT WOS:000305900700024 PM 24653832 ER PT J AU Bryant, MS Rintala, DH Hou, JG Rivas, SP Fernandez, AL Lai, EC Protas, EJ AF Bryant, M. S. Rintala, D. H. Hou, J. G. Rivas, S. P. Fernandez, A. L. Lai, E. C. Protas, E. J. TI The Relation of Falls to Fatigue, Depression and Daytime Sleepiness in Parkinson's Disease SO EUROPEAN NEUROLOGY LA English DT Article DE Parkinson's disease; Fatigue; Depressive symptomatology; Falls; Non-motor symptoms; Sleepiness ID QUALITY-OF-LIFE; NONMOTOR SYMPTOMS; RISK-FACTORS; SCALE; PREVALENCE; ATTENTION; SEVERITY; PEOPLE; SAMPLE AB Objective: To characterize non-motor symptoms in individuals with Parkinson's disease (PD) who experience falls compared to those who do not fall. Methods: Fifty-four individuals with PD were studied. Thirty-six were fallers and 18 were non-fallers. Fatigue was assessed by the Iowa Fatigue Scale. Excessive daytime sleepiness was assessed by the Epworth Sleepiness Scale, and depressive symptomatology was assessed by the short-form Center for Epidemiologic Studies Depression Scale. Results: Compared to non-fallers, fallers had more severe disability, greater general physical fatigue (p = 0.024), lower energy levels (p = 0.042) and less productivity (p = 0.007). Fallers had more depressive symptomatology than the non-fallers (p = 0.01). Excessive daytime sleepiness was not different between the two groups (p = 0.695). Conclusions: Individuals with PD who fell had more severe motor and non-motor symptoms than those who did not fall. These non-motor symptoms included physical fatigue, energy, productivity and depressive symptomatology. Copyright (C) 2012 S. Karger AG, Basel C1 [Bryant, M. S.; Rivas, S. P.; Fernandez, A. L.; Protas, E. J.] Univ Texas Med Branch, Sch Hlth Profess, Galveston, TX USA. [Bryant, M. S.; Rintala, D. H.] Baylor Coll Med, Dept Phys Med & Rehabil, Houston, TX 77030 USA. [Bryant, M. S.; Hou, J. G.] Baylor Coll Med, Michael E DeBakey Vet Affairs Med Ctr, Houston, TX 77030 USA. [Hou, J. G.] Baylor Coll Med, Dept Neurol, Houston, TX 77030 USA. [Lai, E. C.] Methodist Neurol Inst, Houston, TX USA. RP Bryant, MS (reprint author), Rehabil Res MEDVAMC 153, 2002 Holcombe Blvd, Houston, TX 77030 USA. EM mon.bryant@yahoo.com FU Eunice Kennedy Shriver National Institute of Child Health and Human Development [K12 HD055929, R01 HD051844]; National Institute of Neurological Disorders and Stroke FX This work was supported in part by grant K12 HD055929 from the Eunice Kennedy Shriver National Institute of Child Health and Human Development and the National Institute of Neurological Disorders and Stroke and grant R01 HD051844 from the Eunice Kennedy Shriver National Institute of Child Health and Human Development. NR 45 TC 8 Z9 8 U1 0 U2 8 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0014-3022 J9 EUR NEUROL JI Eur. Neurol. PY 2012 VL 67 IS 6 BP 326 EP 330 DI 10.1159/000335877 PG 5 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 966ZG UT WOS:000305875300002 PM 22555623 ER PT J AU Granziera, C Ay, H Koniak, SP Krueger, G Sorensen, AG AF Granziera, Cristina Ay, Hakan Koniak, Susan P. Krueger, Gunnar Sorensen, A. Gregory TI Diffusion Tensor Imaging Shows Structural Remodeling of Stroke Mirror Region: Results from a Pilot Study SO EUROPEAN NEUROLOGY LA English DT Article DE Stroke recovery; Diffusion tensor imaging; Plasticity; Contralesional hemisphere ID WATER DIFFUSION; CONTRALESIONAL HEMISPHERE; LONGITUDINAL FMRI; MOTOR RECOVERY; HUMAN BRAIN; CORTEX; REORGANIZATION; PROJECTIONS; ANISOTROPY; PATHWAYS AB Background: The role of the non-injured hemisphere in stroke recovery is poorly understood. In this pilot study, we sought to explore the presence of structural changes detectable by diffusion tensor imaging (DTI) in the contralesional hemispheres of patients who recovered well from ischemic stroke. Methods: We analyzed serial DTI data from 16 stroke patients who had moderate initial neurological deficits (NIHSS scores 3-12) and good functional outcome at 3-6 months (NIHSS score 0 or modified Rankin Score <= 1). We segmented the brain tissue in gray and white matter (GM and WM) and measured the apparent diffusion coefficient (ADC) and fractional anisotropy in the infarct, in the contralesional infarct mirror region as well as in concentrically expanding regions around them. Results: We found that GM and WM ADC significantly increased in the infarct region (p < 0.01) from acute to chronic time points, whereas in the infarct mirror region, GM and WM ADC increased (p < 0.01) and WM fractional anisotropy decreased (p < 0.05). No significant changes were detected in other regions. Conclusion: DTI-based metrics are sensitive to regional structural changes in the contralesional hemisphere during stroke recovery. Prospective studies in larger cohorts with varying levels of recovery are needed to confirm our findings. Copyright (C) 2012 S. Karger AG, Basel C1 [Granziera, Cristina] CHU Vaudois, Dept Clin Neurosci, CH-1011 Lausanne, Switzerland. [Granziera, Cristina; Ay, Hakan; Sorensen, A. Gregory] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Koniak, Susan P.] Boston Univ, Boston, MA 02215 USA. [Granziera, Cristina] Univ Lausanne, Lausanne, Switzerland. [Krueger, Gunnar] Siemens Schweiz AG, Healthcare Sect IM&WS S, Rennes, France. [Sorensen, A. Gregory] Siemens Healthcare N Amer, Tarrytown, NY USA. RP Granziera, C (reprint author), CHU Vaudois, Dept Clin Neurosci, CH-1011 Lausanne, Switzerland. EM cristina.granziera@chuv.ch FU Swiss Heart Foundation; NIH [R01-NS059710] FX We thank Dr. Ashok Kumar for invaluable help in data processing. C.G. was supported by the Swiss Heart Foundation. H.A. was funded by NIH grant R01-NS059710. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 29 TC 5 Z9 6 U1 0 U2 4 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0014-3022 J9 EUR NEUROL JI Eur. Neurol. PY 2012 VL 67 IS 6 BP 370 EP 376 DI 10.1159/000336062 PG 7 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 966ZG UT WOS:000305875300009 PM 22614706 ER PT J AU Kumar, M Singh, G Arora, V Mewar, S Sharma, U Jagannathan, NR Sapra, S Dinda, AK Kharbanda, S Singh, H AF Kumar, Manoj Singh, Gurpal Arora, Vikas Mewar, Sujeet Sharma, Uma Jagannathan, N. R. Sapra, Sameer Dinda, Amit K. Kharbanda, Surender Singh, Harpal TI Cellular interaction of folic acid conjugated superparamagnetic iron oxide nanoparticles and its use as contrast agent for targeted magnetic imaging of tumor cells SO INTERNATIONAL JOURNAL OF NANOMEDICINE LA English DT Article DE superparamagnetic iron oxide nanoparticles (SPION); cellular internalization; magnetic resonance imaging (MRI); cancer-cell targeting ligand ID IN-VIVO; PHYSICOCHEMICAL CHARACTERISTICS; INTRACELLULAR UPTAKE; DRUG-DELIVERY; PARTICLE-SIZE; CANCER-CELLS; ENDOCYTOSIS; FUNCTIONALIZATION; NANOCRYSTALS; TISSUES AB The purpose of the study was to develop tumor specific, water dispersible superparamagnetic iron oxide nanoparticles (SPIONs) and evaluate their efficacy as a contrast agent in magnetic resonance imaging (MRI). We have developed SPIONs capped with citric acid/2-bromo-2-methylpropionic acid which are compact, water dispersible, biocompatible having narrow range of size dispersity (8-10 nm), and relatively high T-2 relaxivity (R-2 = 222L.mmol(-1).sec(-l)). The targeting efficacy of unconjugated and folic acid-conjugated SPIONs (FA-SPIONS) was evaluated in a folic acid receptor overexpressing and negative tumor cell lines. Folic acid receptor-positive cells incubated with FA-SPIONs showed much higher intracellular iron content without any cytotoxicity. Ultrastructurally, SPIONs were seen as clustered inside the various stages of endocytic pathways without damaging cellular organelles and possible mechanism for their entry is via receptor mediated endocytosis. In vitro MRI studies on tumor cells showed better T-2-weighted images in FA-SPIONs. These findings indicate that FA-SPIONs possess high colloidal stability with excellent sensitivity of imaging and can be a useful MRI contrast agent for the detection of cancer. C1 [Kumar, Manoj; Singh, Gurpal; Singh, Harpal] Indian Inst Technol, Ctr Biomed Engn, New Delhi 110016, India. [Arora, Vikas; Sapra, Sameer] Indian Inst Technol, Dept Chem, New Delhi 110016, India. [Mewar, Sujeet; Sharma, Uma; Jagannathan, N. R.] All India Inst Med Sci, Dept NMR, New Delhi 110029, India. [Dinda, Amit K.] All India Inst Med Sci, Dept Pathol, New Delhi 110029, India. [Kharbanda, Surender] Harvard Univ, Dept Med Oncol, Dana Farber Canc Inst, Sch Med, Boston, MA 02115 USA. RP Singh, H (reprint author), Indian Inst Technol, Ctr Biomed Engn, Hauz Khas, New Delhi 110016, India. EM amit_dinda@yhaoo.com; harpal2000@yahoo.com RI Sapra, Sameer/I-3551-2012; OI Sapra, Sameer/0000-0002-1778-2884 FU Lockheed Martin Corporation (NJ, USA); Department of Science and Technology, Govt of India; Council of Scientific and Industrial Research FX The authors gratefully acknowledge Lockheed Martin Corporation (NJ, USA), Department of Science and Technology, Govt of India and Council of Scientific and Industrial Research for financial assistance and Supported Accommodation Innovation Fund, SAIF, AIIMS for TEM studies. NR 46 TC 33 Z9 33 U1 1 U2 40 PU DOVE MEDICAL PRESS LTD PI ALBANY PA PO BOX 300-008, ALBANY, AUCKLAND 0752, NEW ZEALAND SN 1178-2013 J9 INT J NANOMED JI Int. J. Nanomed. PY 2012 VL 7 BP 3503 EP 3516 DI 10.2147/IJN.S32694 PG 14 WC Nanoscience & Nanotechnology; Pharmacology & Pharmacy SC Science & Technology - Other Topics; Pharmacology & Pharmacy GA 970BP UT WOS:000306103400001 PM 22848174 ER PT J AU Timucin, C Gul, O Kutuk, O Basaga, H AF Timucin, Can Gul, Ozgur Kutuk, Ozgur Basaga, Huveyda TI ANTIBODY ARRAY-BASED IMMUNOSENSOR FOR DETECTING CARDIOVASCULAR DISEASE RISK MARKERS SO JOURNAL OF IMMUNOASSAY & IMMUNOCHEMISTRY LA English DT Article DE ELISA; method comparison; multiplexed immunosensor; myoglobin; serum amyloid a; vascular cell adhesion molecule ID PROTEIN; ELISA; MICROARRAYS; TECHNOLOGIES; CHALLENGES; VALIDATION; BIOMARKERS; CYTOKINES; ASSAYS AB Quantitative detection of proteins in multiplexed platforms presents technical advantages at clinical and laboratory settings compared to the monoplex ELISA method. With this purpose, we implemented a pilot study using in-house-designed sandwich-type antibody array for multiplexed detection of seven cardiovascular disease (CVD) risk markers and compared the performance of our immunosensor to conventional ELISA kits. Results indicated that our immunosensor can determine serum amyloid A (SAA), vascular cell adhesion molecule (VCAM), and myoglobin (MYO) concentrations accurately, precisely, and above all very much similar to ELISA. Hence, multiplexed detection and quantification of SAA, VCAM, and MYO with our immunosensor can be considered as a potential multiplexed alternative to the ELISA method. C1 [Basaga, Huveyda] Sabanci Univ, Fac Engn & Nat Sci, Biol Sci & Bioengn Program, TR-34956 Istanbul, Turkey. [Kutuk, Ozgur] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Basaga, H (reprint author), Sabanci Univ, Fac Engn & Nat Sci, Biol Sci & Bioengn Program, TR-34956 Istanbul, Turkey. EM huveyda@sabanciuniv.edu OI Timucin, Ahmet Can/0000-0002-9483-3593 FU Scientific and Technological Research Council of Turkey (TUBITAK) [TUBITAK-SBAG-104S380] FX We would like to thank the Scientific and Technological Research Council of Turkey (TUBITAK) for the financial support provided for this study with a contract number TUBITAK-SBAG-104S380. We would also like to acknowledge the contributions of Bayer Cinar and Cuneyt Konuralp for supplying the CVD patient group samples. NR 25 TC 3 Z9 3 U1 2 U2 21 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1532-1819 J9 J IMMUNOASS IMMUNOCH JI J. Immunoass. Immunoch. PY 2012 VL 33 IS 3 BP 275 EP 290 DI 10.1080/15321819.2011.638407 PG 16 WC Biochemical Research Methods; Immunology; Medical Laboratory Technology SC Biochemistry & Molecular Biology; Immunology; Medical Laboratory Technology GA 968DK UT WOS:000305957000005 PM 22738651 ER PT J AU Gerber, MR Fried, LE Pineles, SL Shipherd, JC Bernstein, CA AF Gerber, Megan R. Fried, Lise E. Pineles, Suzanne L. Shipherd, Jillian C. Bernstein, Carolyn A. TI Posttraumatic Stress Disorder and Intimate Partner Violence in a Women's Headache Center SO WOMEN & HEALTH LA English DT Article DE posttraumatic stress disorder; intimate partner violence; headache; chronic pain; disability ID NATIONAL COMORBIDITY SURVEY; SHORT SCREENING SCALE; PRIMARY-CARE PATIENTS; CHRONIC PAIN; MIGRAINE DISABILITY; TRAUMA EXPOSURE; PHYSICAL HEALTH; SEXUAL-ABUSE; SYMPTOMS; PTSD AB Background: Posttraumatic stress disorder has been linked to women's ill health, including headaches. Intimate partner violence, which may result in posttraumatic stress disorder, is often reported by women with headaches. Prior studies of intimate partner violence and headache have estimated lifetime but not 12-month prevalence. The researchers in this study examined the relationship between headache and posttraumatic stress disorder in a novel population, and estimated 12-month and lifetime prevalence rates of intimate partner violence. Methods: Patients were recruited from a women's headache center (n = 92) during 2006-07 and wompleted the Migraine Disability Assessment measure of headache severity. Posttraumatic stress disorder was measured using a modified Breslau scale. Twelve-month and lifetime physical intimate partner violence were measured with the Partner Violence Screen and the STaT ("slapped, threatened and throw") measure. Multivariable regression determined factors independently associated with headache severity. Results: Among all participants, 28.3% screened positive for posttraumatic stress disorder; 9.8% and 36.9% of women endorsed recent and lifetime intimate partner violence. Posttraumatic stress disorder was strongly associated with headache severity (beta = 34.12, p = 0.01). Patients reporting lifetime intimate partner violence exhibited a trend of nine additional days of disability due to headache over 90 days. Conclusions: Posttraumatic stress disorder and intimate partner violence occur among a sizable proportion of women referred for headache. The authors' findings reaffirm that clinicians treating women with headaches must be aware of the possibility of posttraumatic stress disorder and intimate partner violence in such patients. C1 [Gerber, Megan R.] Boston Univ, Sch Med, VA Boston Healthcare Syst Womens Hlth, Boston, MA 02118 USA. [Fried, Lise E.] Harvard Univ, Sch Med, Inst Community Hlth, Cambridge, MA 02138 USA. [Pineles, Suzanne L.; Shipherd, Jillian C.] Boston Univ, Sch Med, VA Boston Healthcare Syst, Natl Ctr PTSD,Womens Hlth Sci Div, Boston, MA 02118 USA. [Bernstein, Carolyn A.] Harvard Univ, Beth Israel Deaconess Med Ctr, Harvard Med Fac, Phys Comprehens Headache Ctr,Med Sch, Boston, MA 02215 USA. RP Gerber, MR (reprint author), Boston Univ, Sch Med, VA Boston Healthcare Syst Womens Hlth, 150 S Huntington Ave, Jamaica Plain, MA 02130 USA. EM megan.gerber@va.gov OI Gerber, Megan/0000-0002-8444-5554 NR 72 TC 5 Z9 5 U1 1 U2 9 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 0363-0242 EI 1541-0331 J9 WOMEN HEALTH JI Women Health PY 2012 VL 52 IS 5 BP 454 EP 471 DI 10.1080/03630242.2012.684088 PG 18 WC Public, Environmental & Occupational Health; Women's Studies SC Public, Environmental & Occupational Health; Women's Studies GA 968MZ UT WOS:000305987400003 PM 22747183 ER PT J AU Bansal, N Hsu, CY Whooley, M Berg, AH Ix, JH AF Bansal, Nisha Hsu, Chi-yuan Whooley, Mary Berg, Anders H. Ix, Joachim H. TI Relationship of Urine Dopamine with Phosphorus Homeostasis in Humans: The Heart and Soul Study SO AMERICAN JOURNAL OF NEPHROLOGY LA English DT Article DE Urine dopamine; Phosphorus; Kidney; Proximal tubule ID CORONARY-ARTERY-DISEASE; PHOSPHATE EXCRETION; CYSTATIN-C; CARDIOVASCULAR-DISEASE; DEPRESSIVE SYMPTOMS; PARATHYROID-HORMONE; SERUM PHOSPHORUS; REMNANT KIDNEY; RENAL DOPAMINE; OK CELLS AB Background: Urine dopamine (DA) is produced in the proximal tubule and has been found to increase in response to dietary phosphorus intake, and to contribute to greater urinary phosphorus excretion in animal models. Whether urine DA is associated with phosphorus homeostasis in humans is uncertain. Methods: This was a cross-sectional study of 884 outpatients. DA was measured from 24-hour urine collections. We examined cross-sectional associations between urine DA and serum phosphorus, 24-hour urine phosphorus (as an indicator of dietary phosphorus absorption), fractional excretion of phosphorus (FEphos), fibroblast growth factor (FGF)-23, and parathyroid hormone (PTH). Models were adjusted for age, sex, race, eGFR, albuminuria, hypertension, heart failure, tobacco use, body mass index, and diuretic use. Results: Mean age was 66.6 +/- 11 years and mean eGFR was 71 +/- 21.3 ml/min/1.73 m(2). The mean urine DA was 193 +/- 86 mu g/day, mean serum phosphorus was 3.6 +/- 0.6 mg/dl, mean daily urine phosphorus excretion was 671 8 312 mg/day, and mean FEphos was 17 +/- 9%. In adjusted models, each standard deviation higher DA was associated with 78.4 mg/day higher urine phosphorus and 0.9% lower FEphos (p < 0.05 for both). There was no statistically significant association between urine DA, serum phosphorus, FGF-23 or PTH in adjusted models. Conclusions: Higher dietary phosphorus absorption is associated with higher urine DA in humans, consistent with animal models. However, higher urine DA is not associated with FGF-23 or PTH, suggesting that known mechanisms of renal tubular handling of phosphorus may not be involved in the renal dopamine-phosphorus regulatory pathway in humans. Copyright (C) 2012 S. Karger AG, Basel C1 [Bansal, Nisha] Univ Calif San Francisco, Div Nephrol, Dept Med, San Francisco, CA 94143 USA. [Whooley, Mary] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Whooley, Mary] San Francisco VA Med Ctr, San Francisco, CA USA. [Berg, Anders H.] Beth Israel Deaconess Med Ctr, Dept Pathol, Boston, MA 02215 USA. [Ix, Joachim H.] Vet Affairs San Diego Healthcare Syst, Nephrol Sect, San Diego, CA USA. [Ix, Joachim H.] Univ Calif San Diego, Dept Med, Div Nephrol, San Diego, CA 92103 USA. [Ix, Joachim H.] Univ Calif San Diego, Dept Family & Preventat Med, Div Preventat Med, San Diego, CA 92103 USA. RP Bansal, N (reprint author), Univ Calif San Francisco, Div Nephrol, Dept Med, 521 Parnassus Ave,Box 0532, San Francisco, CA 94143 USA. EM nisha.bansal@ucsf.edu FU American Kidney Fund; National Institute of Diabetes and Digestive and Kidney Diseases [K23 DK088865, K24 DK92291]; National Heart Lung and Blood Institute [1R01HL096851]; American Heart Association; Sandra Daugherty Foundation; Department of Veterans Affairs; American Federation of Aging Research; Robert Wood Johnson Foundation; Nancy Kirwan Heart Research Fund; Ischemia Research and Education Foundation; NHLBI [R01 HL079235] FX This study was supported by grants from the American Kidney Fund (N.B.), National Institute of Diabetes and Digestive and Kidney Diseases (K23 DK088865 to N.B. and K24 DK92291 to C.H.), National Heart Lung and Blood Institute (1R01HL096851) (J.H.I.), an American Heart Association Fellow-to-Faculty Transition Award (J.H.I.), and an award from the Sandra Daugherty Foundation (J.H.I.). The Heart and Soul Study was funded by the Department of Veterans Affairs, American Federation of Aging Research, Robert Wood Johnson Foundation, Nancy Kirwan Heart Research Fund, Ischemia Research and Education Foundation, and the NHLBI (R01 HL079235). NR 28 TC 1 Z9 1 U1 0 U2 15 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0250-8095 J9 AM J NEPHROL JI Am. J. Nephrol. PY 2012 VL 35 IS 6 BP 483 EP 490 DI 10.1159/000338483 PG 8 WC Urology & Nephrology SC Urology & Nephrology GA 966BP UT WOS:000305812100001 PM 22572568 ER PT S AU McBride, SM Taghian, AG AF McBride, Sean M. Taghian, Alphonse G. BE Taghian, AG Halyard, MY TI The History of Local Treatment for Breast Cancer SO BREAST CANCER SE Radiation Medicine Rounds LA English DT Article; Book Chapter DE breast cancer; local; history ID RANDOMIZED CLINICAL-TRIAL; COMPARING TOTAL MASTECTOMY; RADICAL-MASTECTOMY; PREMENOPAUSAL WOMEN; NATURAL-HISTORY; RADIOTHERAPY; CHEMOTHERAPY; IRRADIATION; METASTASES; LUMPECTOMY AB The historical tale of how the current standard of care for breast cancer local therapy evolved involves the rise and fall of prominent physicians and theories. From Halsted to Fisher, the pitched battles over the role and importance of the radical mastectomy and the theories on how cancer spread that were used to justify, the varieties of treatment consumed generations of oncologists. In this chapter, we attempt to summarize this history, providing insight into the key personalities and the crucial theoretical breakthroughs that brought us into the modern era. C1 [McBride, Sean M.; Taghian, Alphonse G.] Harvard Univ, Dept Radiat Oncol, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. [McBride, Sean M.] Harvard Univ, Harvard Radiat Oncol Program, Sch Med, Boston, MA 02114 USA. RP McBride, SM (reprint author), Harvard Univ, Dept Radiat Oncol, Massachusetts Gen Hosp, Sch Med, Cox 3,100 Blossom St, Boston, MA 02114 USA. EM smcbride@lroc.harvard.edu NR 42 TC 1 Z9 1 U1 0 U2 0 PU DEMOS MEDICAL PUBLICATIONS PI NEW YORK PA 11 WEST 42ND STREET, 15TH FLOOR, NEW YORK, NY 10036 USA SN 2151-4208 BN 978-1-936287-65-9 J9 RADIAT MED ROUNDS PY 2012 VL 3 IS 1 BP 1 EP 14 DI 10.5003/2151-4208.3.1.1 PG 14 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA BAI68 UT WOS:000304281300001 ER PT S AU Arvold, ND Taghian, AG AF Arvold, Nils D. Taghian, Alphonse G. BE Taghian, AG Halyard, MY TI Local Recurrence and Biological Subtypes of Breast Cancer SO BREAST CANCER SE Radiation Medicine Rounds LA English DT Article; Book Chapter DE breast-cancer; subtype; local recurrence; locoregional recurrence; breast-conserving therapy; mastectomy; luminal; HER2; triple negative ID CONSERVING THERAPY; GENE-EXPRESSION; ADJUVANT CHEMOTHERAPY; PROGESTERONE-RECEPTOR; MOLECULAR PORTRAITS; ESTROGEN-RECEPTOR; YOUNG AGE; PROGNOSIS; RISK; SURVIVAL AB Estimation of the risk of local and regional recurrence after treatment for early stage breast cancer has long relied on traditional clinical and pathologic prognostic factors, but these remain imprecise. With the discovery of intrinsic breast cancer subtypes based on gene expression profiling, there has been great interest in determining the value of these subtypes as prognostic and predictive factors. Several retrospective reports have now examined the risk of local and regional recurrence after breast-conserving therapy or mastectomy according to immunohistochemistry-based approximations of the molecular subtypes. Luminal breast cancers, defined by hormone receptor positivity, have been found to have markedly improved local outcomes as compared to nonluminal breast cancers. Further work is required to prospectively, validate the use of breast cancer subtypes as prognostic and/or predictive markers for eventual clinical use with individual patients. C1 [Taghian, Alphonse G.] Harvard Univ, Dept Radiat Oncol, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. [Arvold, Nils D.] Harvard Univ, Sch Med, Harvard Radiat Oncol Program, Boston, MA USA. RP Taghian, AG (reprint author), Harvard Univ, Dept Radiat Oncol, Massachusetts Gen Hosp, Sch Med, Mailstop Cox 3,100 Blossom St, Boston, MA 02114 USA. EM ataghian@partners.org; ataghian@partners.org NR 30 TC 0 Z9 0 U1 0 U2 1 PU DEMOS MEDICAL PUBLICATIONS PI NEW YORK PA 11 WEST 42ND STREET, 15TH FLOOR, NEW YORK, NY 10036 USA SN 2151-4208 BN 978-1-936287-65-9 J9 RADIAT MED ROUNDS PY 2012 VL 3 IS 1 BP 99 EP 106 DI 10.5003/2151-4208.3.1.99 PG 8 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA BAI68 UT WOS:000304281300008 ER PT S AU MacDonald, SM AF MacDonald, Shannon M. BE Taghian, AG Halyard, MY TI Proton Radiation for Breast Cancer SO BREAST CANCER SE Radiation Medicine Rounds LA English DT Article; Book Chapter DE proton radiation; breast cancer ID CONTRALATERAL PROPHYLACTIC MASTECTOMY; 3-DIMENSIONAL CONFORMAL RADIOTHERAPY; ADJUVANT CHEMOTHERAPY; RANDOMIZED-TRIAL; POSTOPERATIVE RADIOTHERAPY; PREMENOPAUSAL WOMEN; THERAPY; IRRADIATION; PNEUMONITIS; RISK AB Proton therapy allows for radiation delivery to targeted areas with decreased radiation dose to healthy surrounding tissues when compared with standard radiation. For many malignancies, the goal of using proton therapy is to decrease the side effects from radiation therapy. Clinical experience for the use of protons for breast malignancies to date is limited. Given the increased access to this form of therapy and the potential for long-term survival for breast cancer patients, we are beginning to explore the potential benefits of this form of radiation. Clinical trials are starting to explore the best indications for this more expensive form of radiation treatment. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Boston, MA 02114 USA. RP MacDonald, SM (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Boston, MA 02114 USA. EM smacdonald@partners.org NR 44 TC 0 Z9 0 U1 1 U2 1 PU DEMOS MEDICAL PUBLICATIONS PI NEW YORK PA 11 WEST 42ND STREET, 15TH FLOOR, NEW YORK, NY 10036 USA SN 2151-4208 BN 978-1-936287-65-9 J9 RADIAT MED ROUNDS PY 2012 VL 3 IS 1 BP 119 EP 127 DI 10.5003/2151-4208.3.1.119 PG 9 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA BAI68 UT WOS:000304281300010 ER PT B AU Beaser, RS Snow, K Rizzotto, JAM Brown, J Abrahamson, MJ AF Beaser, Richard S. Snow, Kenneth Rizzotto, Jo-Anne M. Brown, Julie Abrahamson, Martin J. BE Harrington, JT Newman, ED TI Diabetes: Everyone's Number One Priority SO GREAT HEALTH CARE: MAKING IT HAPPEN LA English DT Article; Book Chapter DE Diabetes; Joslincare; Partnership; Communication; Customer service; Multidiscipinary teams; Joslin affiliates; Joslin professional education continuum ID CONTINUING MEDICAL-EDUCATION; SELF-ASSESSMENT; CLINICAL-PRACTICE; COMPLICATIONS; ASSOCIATION; PERFORMANCE; STRATEGIES; MELLITUS; US C1 [Beaser, Richard S.; Snow, Kenneth; Rizzotto, Jo-Anne M.; Brown, Julie; Abrahamson, Martin J.] Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA. RP Beaser, RS (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA. EM Richard.Beaser@joslin.harvard.edu NR 26 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 978-1-4614-1197-0 PY 2012 BP 101 EP 112 DI 10.1007/978-1-4614-1198-7_13 D2 10.1007/978-1-4614-1198-7 PG 12 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA BAB52 UT WOS:000303690200013 ER PT J AU Nieuwsma, JA Trivedi, RB McDuffie, J Kronish, I Benjamin, D Williams, JW AF Nieuwsma, Jason A. Trivedi, Ranak B. McDuffie, Jennifer Kronish, Ian Benjamin, Dinesh Williams, John W., Jr. TI BRIEF PSYCHOTHERAPY FOR DEPRESSION: A SYSTEMATIC REVIEW AND META-ANALYSIS SO INTERNATIONAL JOURNAL OF PSYCHIATRY IN MEDICINE LA English DT Review DE depression; psychotherapy; primary healthcare; meta-analysis; review; systematic; psychotherapy; brief ID RANDOMIZED CONTROLLED-TRIAL; PROBLEM-SOLVING TREATMENT; PRIMARY-CARE PATIENTS; COGNITIVE-BEHAVIOR THERAPY; MINOR DEPRESSION; MAJOR DEPRESSION; TELEPHONE PSYCHOTHERAPY; DYSTHYMIA; DISORDER; MINDFULNESS AB Objective: Because evidence-based psychotherapies of 12 to 20 sessions can be perceived as too lengthy and time intensive for the treatment of depression in primary care, a number of studies have examined abbreviated psychotherapy protocols. The purpose of this study was to conduct a systematic review and meta-analysis to determine the efficacy of brief psychotherapy (i.e., <= 8 sessions) for depression. Methods: We used combined literature searches in PubMed, EMBASE, PsycINFO, and an Internet-accessible database of clinical trials of psychotherapy to conduct two systematic searches: one for existing systematic reviews and another for randomized controlled trials (RCTs). Included studies examined evidence-based psychotherapy(s) of eight or fewer sessions, focused on adults with depression, contained an acceptable control condition, were published in English, and used validated measures of depressive symptoms. Results: We retained 2 systematic reviews and 15 RCTs evaluating cognitive behavioral therapy, problem-solving therapy, and mindfulness-based cognitive therapy. The systematic reviews found brief psychotherapies to be more efficacious than control, with effect sizes ranging from -0.33 to -0.25. Our meta-analysis found six to eight sessions of cognitive behavioral therapy to be more efficacious than control (ES -0.42, 95% CI -0.74 to -0.10, I-2 = 56%). A sensitivity analysis controlled for statistical heterogeneity but showed smaller treatment effects (ES -0.24, 95% Cl -0.42 to -0.06, I-2 = 0%). Conclusions: Depression can be efficaciously treated with six to eight sessions of psychotherapy, particularly cognitive behavioral therapy and problem-solving therapy. Access to non-pharmacologic treatments for depression could be improved by training healthcare providers to deliver brief psychotherapies. (Inn. J. Psychiatry in Medicine 2012;43:129-151) C1 [Nieuwsma, Jason A.] Durham VA MIRECC, Durham, NC USA. [Nieuwsma, Jason A.; McDuffie, Jennifer; Williams, John W., Jr.] Duke Univ, Med Ctr, Durham, NC 27706 USA. [Trivedi, Ranak B.] VA Puget Sound Hlth Care Syst, Seattle, WA USA. [Trivedi, Ranak B.] Univ Washington, Seattle, WA 98195 USA. [McDuffie, Jennifer; Williams, John W., Jr.] Durham VA Evidence Synth Program, Durham, NC USA. [Kronish, Ian] Columbia Univ, Med Ctr, New York, NY 10027 USA. [Benjamin, Dinesh] Carolina Behav Care, Durham, NC USA. RP Nieuwsma, JA (reprint author), VA Midatlantic MIRECC, Legacy Towers 800B,411 W Chapel Hill St, Durham, NC 27701 USA. EM jason.nieuwsma@duke.edu OI Kronish, Ian/0000-0003-0945-2380 FU Department of Veterans Affairs FX The Department of Veterans Affairs Evidence-based Synthesis Program funded this review. The views and opinions in this manuscript are those of the authors and do not reflect those of the VA. NR 46 TC 17 Z9 17 U1 1 U2 18 PU BAYWOOD PUBL CO INC PI AMITYVILLE PA 26 AUSTIN AVE, PO BOX 337, AMITYVILLE, NY 11701 USA SN 0091-2174 J9 INT J PSYCHIAT MED JI Int. J. Psychiatr. Med. PY 2012 VL 43 IS 2 BP 129 EP 151 DI 10.2190/PM.43.2.c PG 23 WC Psychiatry SC Psychiatry GA 964WP UT WOS:000305727700003 PM 22849036 ER PT J AU Gard, T Brach, N Holzel, BK Noggle, JJ Conboy, LA Lazar, SW AF Gard, Tim Brach, Narayan Hoelzel, Britta K. Noggle, Jessica J. Conboy, Lisa A. Lazar, Sara W. TI Effects of a yoga-based intervention for young adults on quality of life and perceived stress: The potential mediating roles of mindfulness and self-compassion SO JOURNAL OF POSITIVE PSYCHOLOGY LA English DT Article DE yoga; mindfulness; self-compassion; quality of life; perceived stress; young adults ID REDUCTION INTERVENTION; SATISFACTION; HEALTH; ADOLESCENTS; HAPPINESS; BENEFITS; VALIDITY; STUDENTS; PROGRAM; DESIGN AB The purpose of this pilot study was to investigate the effects of a yoga-based program on quality of life, perceived stress, mindfulness, and self-compassion in young adults. These variables were measured in 33 self-selected participants of a four-month residential yoga intervention before and after the program. Forty-three demographically matched controls completed the same questionnaires at two time points with a four-month interval inbetween. Participation in the program predicted increases in quality of life and decreases in perceived stress, mediated by mindfulness and self-compassion. Multiple mediator models revealed that the effect of group on quality of life was simultaneously mediated by mindfulness and self-compassion, while the effect of group on perceived stress was only mediated by self-compassion. These positive effects on perceived stress and quality of life suggest that yoga-based interventions may be of value in cultivating subjective well-being in young adults. Furthermore, yoga-based and mindfulness-based interventions may share underlying mechanisms. C1 [Gard, Tim; Brach, Narayan; Hoelzel, Britta K.; Lazar, Sara W.] Massachusetts Gen Hosp, Dept Psychiat, Charlestown, MA 02129 USA. [Gard, Tim; Hoelzel, Britta K.] Univ Giessen, Bender Inst Neuroimaging, D-35390 Giessen, Germany. [Hoelzel, Britta K.; Noggle, Jessica J.; Conboy, Lisa A.; Lazar, Sara W.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Noggle, Jessica J.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Conboy, Lisa A.] New England Sch Acupuncture, Newton, MA 02458 USA. RP Gard, T (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Charlestown, MA 02129 USA. EM tgard@nmr.mgh.harvard.edu RI Lazar, Sara/G-3809-2012 OI Lazar, Sara/0000-0003-1126-8363 NR 61 TC 20 Z9 20 U1 6 U2 59 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 1743-9760 J9 J POSIT PSYCHOL JI J. Posit. Psychol. PY 2012 VL 7 IS 3 BP 165 EP 175 DI 10.1080/17439760.2012.667144 PG 11 WC Psychology, Multidisciplinary SC Psychology GA 965WC UT WOS:000305797200001 ER PT J AU Mariano, JM Vaillant, GE AF Mariano, Jenni Menon Vaillant, George E. TI Youth purpose among the 'greatest generation' SO JOURNAL OF POSITIVE PSYCHOLOGY LA English DT Article DE adolescents; college students; goal-setting and planning; purpose; youth purpose; emerging adulthood ID EMERGING ADULTHOOD; ADOLESCENCE; LIFE; INTELLIGENCE; HAPPINESS AB Purpose is a stable and generalized intention to accomplish something that is at once important to self and directed at making a difference in the world beyond the self. In the present study, ratings of one aspect of purpose, pro-social beyond-the-self intentions, were gleaned from data collected from young men attending college between 1938 and 1942 as a part of the Study of Adult Development. Associations were examined between pro-social beyond-the-self intentions and childhood environment, and between pro-social beyond-the-self intentions and college and adult personality, psychological adjustment, and achievement. Higher levels of pro-social beyond-the-self intentions were associated with informant ratings of global impressions of positive childhood environment, and with humanistic, political, and well-integrated personality dispositions in college. C1 [Mariano, Jenni Menon] Univ S Florida Sarasota Manatee, Coll Educ, Sarasota, FL 34243 USA. [Vaillant, George E.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Vaillant, George E.] Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Mariano, JM (reprint author), Univ S Florida Sarasota Manatee, Coll Educ, 8350 N Tamiami Trail, Sarasota, FL 34243 USA. EM jmmariano@sar.usf.edu NR 51 TC 1 Z9 1 U1 0 U2 4 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 1743-9760 J9 J POSIT PSYCHOL JI J. Posit. Psychol. PY 2012 VL 7 IS 4 BP 281 EP 293 DI 10.1080/17439760.2012.686624 PG 13 WC Psychology, Multidisciplinary SC Psychology GA 965WF UT WOS:000305797500002 ER PT J AU Bogdanov, AA Mazzanti, M Castillo, G Bolotin, E AF Bogdanov, Alexei A., Jr. Mazzanti, Mary Castillo, Gerardo Bolotin, Elijah TI Protected Graft Copolymer (PGC) in Imaging and Therapy: A Platform for the Delivery of Covalently and Non-Covalently Bound Drugs SO THERANOSTICS LA English DT Review DE contrast agent; gaft-copolymer; poly(ethylene glycol); chelate; paramagnetic; gadolinium ID ATRIAL-NATRIURETIC-PEPTIDE; MATRIX-METALLOPROTEINASE ACTIVITY; INFRARED FLUORESCENT-PROBES; CYCLASE-A RECEPTOR; LONG-ACTING GLP-1; POLY-L-LYSINE; IN-VIVO; POLYETHYLENE-GLYCOL; BLOOD-VOLUME; CONTRAST AGENTS AB Initially developed in 1992 as an MR imaging agent, the family of protected graft copolymers (PGC) is based on a conjugate of polylysine backbone to which methoxypoly(ethylene glycol) (MPEG) chains are covalently linked in a random fasion via N-epsilon-amino groups. While PGC is relatively simple in terms of its chemcial composition and structure, it has proved to be a versatile platform for in vivo drug delivery. The advantages of poly amino acid backbone grafting include multiple available linking sites for drug and adaptor molecules. The grafting of PEG chains to PGC does not compromise biodegradability and does not result in measurable toxicity or immunogenicity. In fact, the biocompatablility of PGC has resulted in its being one of the few 100% synthetic non-proteinaceous macromolecules that has suceeded in passing the initial safety phase of clinical trials. PGC is capable of long circulation times after injection into the blood stream and as such found use early on as a carrier system for delivery of paramagnetic imaging compounds for angiography. Other PGC types were later developed for use in nuclear medicine and optical imaging applications in vivo. Recent developments in PGC-based drug carrier formulations include the use of zinc as a bridge between the PGC carrier and zinc-binding proteins and re-engineering of the PGC carrier as a covalent amphiphile that is capabe of binding to hydrophobic residues of small proteins and peptides. At present, PGC-based formulations have been developed and tested in various disease models for: 1) MR imaging local blood circulation in stroke, cancer and diabetes; 2) MR and nuclear imaging of blood volume and vascular permeability in inflammation; 3) optical imaging of proteolytic activity in cancer and inflammation; 4) delivery of platinum(II) compounds for treating cancer; 5) delivery of small proteins and peptides for treating diabetes, obesity and myocardial infarction. This review summarizes the experience accumulated by various research groups that chose to use PGC as a drug delivery platform. C1 [Bogdanov, Alexei A., Jr.] Univ Massachusetts, Sch Med, Dept Radiol, Lab Mol Imaging Probes, Worcester, MA 01655 USA. [Castillo, Gerardo; Bolotin, Elijah] PharmaIn Corp, Seattle, WA USA. [Castillo, Gerardo; Bolotin, Elijah] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Castillo, Gerardo; Bolotin, Elijah] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Bogdanov, AA (reprint author), Univ Massachusetts, Sch Med, Dept Radiol, Lab Mol Imaging Probes, S6-434,55 Lake Ave N, Worcester, MA 01655 USA. EM Alexei.Bogdanov@umassmed.edu FU NIH [R01CA074424-02, R44AA019584, R44DK069727] FX We are grateful for contributions to PGC applications development to current and former members of the Laboratory of Molecular Imaging Probes (University of Massachusetts Medical School) and Center for Molecular imaging Research (Massachusetts General Hospital). This work was supported by NIH grants: R01CA074424-02, R44AA019584 and R44DK069727. NR 103 TC 13 Z9 13 U1 3 U2 21 PU IVYSPRING INT PUBL PI LAKE HAVEN PA PO BOX 4546, LAKE HAVEN, NSW 2263, AUSTRALIA SN 1838-7640 J9 THERANOSTICS JI Theranostics PY 2012 VL 2 IS 6 BP 553 EP 576 DI 10.7150/thno.4070 PG 24 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 965JY UT WOS:000305765100002 PM 22737192 ER PT J AU Banks, WA AF Banks, W. A. TI The Blood-Brain Barrier: Neuroinflammation and Neurodegenerative Disease SO CELL TRANSPLANTATION LA English DT Meeting Abstract CT 19th Annual Meeting of the American-Society-for-Neural-Therapy-and-Repair CY APR 26-28, 2012 CL Clearwater Beach, FL SP Amer Soc Neural Therapy & Repair C1 [Banks, W. A.] Univ Washington, Sch Med, Dept Med,Div Gerontol & Geriatr Med, Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA 98195 USA. NR 0 TC 0 Z9 0 U1 0 U2 4 PU COGNIZANT COMMUNICATION CORP PI ELMSFORD PA 3 HARTSDALE ROAD, ELMSFORD, NY 10523-3701 USA SN 0963-6897 J9 CELL TRANSPLANT JI Cell Transplant. PY 2012 VL 21 IS 4 BP 773 EP 774 PG 2 WC Cell & Tissue Engineering; Medicine, Research & Experimental; Transplantation SC Cell Biology; Research & Experimental Medicine; Transplantation GA 961VP UT WOS:000305497900016 ER PT J AU Teng, YD Benn, SC Kalkanis, SN Shefner, JM Onario, RC Cheng, B Lachyankar, MB Marconi, M Li, J Maragakis, NJ Llado, J Erkmen, K Redmond, DE Sidman, RL Przedborski, S Rothstein, JD Brown, RH Snyder, EY AF Teng, Y. D. Benn, S. C. Kalkanis, S. N. Shefner, J. M. Onario, R. C. Cheng, B. Lachyankar, M. B. Marconi, M. Li, J. Maragakis, N. J. Llado, J. Erkmen, K. Redmond, D. E., Jr. Sidman, R. L. Przedborski, S. Rothstein, J. D. Brown, R. H., Jr. Snyder, E. Y. TI Neural Stem Cells, Acting Through Multiple Mechanisms, Extensively Prolong Life and Preserve Function in a Mouse Model of ALS: Meta-Analysis of Consortium-Wide Studies SO CELL TRANSPLANTATION LA English DT Meeting Abstract CT 19th Annual Meeting of the American-Society-for-Neural-Therapy-and-Repair CY APR 26-28, 2012 CL Clearwater Beach, FL SP Amer Soc Neural Therapy & Repair C1 [Teng, Y. D.; Kalkanis, S. N.; Onario, R. C.; Erkmen, K.; Sidman, R. L.; Snyder, E. Y.] Harvard Univ, Sch Med, Dept Neurosurg, Boston, MA USA. [Teng, Y. D.; Onario, R. C.] Vet Affairs Boston Healthcare Syst, SCI Res, Boston, MA USA. [Teng, Y. D.; Onario, R. C.; Lachyankar, M. B.; Marconi, M.; Erkmen, K.; Snyder, E. Y.] Harvard Univ, Sch Med, Dept Neurol, Childrens Hosp Boston, Boston, MA 02115 USA. [Benn, S. C.; Kalkanis, S. N.; Brown, R. H., Jr.] Harvard Univ, Sch Med, Dept Neurol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Shefner, J. M.] SUNY Syracuse, Dept Neurol, Syracuse, NY USA. [Cheng, B.] Columbia Univ, Mailman Sch Publ Hlth, Dept Biostat, New York, NY USA. [Marconi, M.; Li, J.; Sidman, R. L.; Snyder, E. Y.] Harvard Univ, Sch Med, Dept Neurol, Beth Israel Deconess Med Ctr, Boston, MA 02115 USA. [Maragakis, N. J.; Llado, J.; Rothstein, J. D.] Johns Hopkins Univ, Dept Neurol, Baltimore, MD 21218 USA. [Redmond, D. E., Jr.] Yale Univ, Sch Med, Dept Psychiat, New Haven, CT USA. [Redmond, D. E., Jr.] Yale Univ, Sch Med, Dept Neurosurg, New Haven, CT USA. [Przedborski, S.] Columbia Univ Coll Phys & Surg, Ctr Neurobiol & Behav, Neurol Inst, Movement Disorder Div, New York, NY 10032 USA. [Brown, R. H., Jr.] Univ Massachusetts, Sch Med, Dept Neurol, Worcester, MA USA. [Snyder, E. Y.] Sanford Burnham Med Res Inst, La Jolla, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU COGNIZANT COMMUNICATION CORP PI ELMSFORD PA 3 HARTSDALE ROAD, ELMSFORD, NY 10523-3701 USA SN 0963-6897 J9 CELL TRANSPLANT JI Cell Transplant. PY 2012 VL 21 IS 4 BP 794 EP 794 PG 1 WC Cell & Tissue Engineering; Medicine, Research & Experimental; Transplantation SC Cell Biology; Research & Experimental Medicine; Transplantation GA 961VP UT WOS:000305497900074 ER PT J AU Algharabli, J Kintner, DB Wang, QW Begum, G Clark, PA Yang, SS Lin, SH Kahle, KT Kuo, JS Sun, DD AF Algharabli, Jehad Kintner, Douglas B. Wang, Qiwei Begum, Gulnaz Clark, Paul A. Yang, Sung-Sen Lin, Shih-Hua Kahle, Kristopher T. Kuo, John S. Sun, Dandan TI Inhibition of Na+-K+-2Cl(-) Cotransporter isoform 1 Accelerates Temozolomide-mediated Apoptosis in Glioblastoma Cancer Cells SO CELLULAR PHYSIOLOGY AND BIOCHEMISTRY LA English DT Article DE Glioblastoma multiforme; Apoptosis; Caspase; Apoptotic volume decrease; Temozolomide Bumetanide ID K+-CL-COTRANSPORTER; HUMAN GLIOMA-CELLS; STEM-CELLS; CHLORIDE CHANNELS; NA-K-2CL COTRANSPORTER; VOLUME REGULATION; NULL MICE; NA+; NEURONS; BRAIN AB The hallmark of apoptosis is a significant reduction in cell volume (AVD) resulting from loss of K-i(+) and Cl-1(-). Loss of cell volume and lowering of ionic strength of intracellular K+ and Cl- occur before any other detectable characteristics of apoptosis. In the present study, temozolomide (TMZ) triggered loss of K-i(+) and Cl-i(-) and AVD in primary glioblastoma multiforme (GBM) cancer cells (GC) and GC cancer stem cells (GSC). We hypothesize that Na+-K+-2Cl(-) cotransporter isoform 1 (NKCC1) counteracts AVD during apoptosis in GBM cancer cells by regulating cell volume and Cl- homeostasis. NKCC1 protein was expressed in both GC and GSC and played an essential role in regulatory volume increase (RVI) in response to hypertonic cell shrinkage and isotonic cell shrinkage. Blocking NKCC1 activity with its potent inhibitor bumetanide abolished RVI. These cells maintained a basal [Cl-](i) ( similar to 68 mM) above the electrochemical equilibrium for Cl-i(-). NKCC1 also functioned to replenish Cl-i(-) levels following the loss of Cl-i(-). TMZ-treated cells exhibited increased phosphorylation of NKCC1 and its up-stream novel Cl-/volume-sensitive regulatory kinase WNK1. Inhibition of NKCC1 activity with bumetanide accelerated AVD, early apoptosis, as well as activation of caspase-3 and caspase-8. Taken together, this study strongly suggests that NKCC1 is an essential mechanism in GBM cells to maintain K+, Cl-, and volume homeostasis to counteract TMZ-induced loss of K+, Cl- and AVD. Therefore, blocking NKCC1 function augments TMZ-induced apoptosis in glioma cells. Copyright (c) 2012S. Karger AG, Basel C1 [Sun, Dandan] Univ Pittsburgh, Sch Med, Dept Neurol, Pittsburgh, PA 15213 USA. [Algharabli, Jehad; Kintner, Douglas B.; Clark, Paul A.; Kuo, John S.; Sun, Dandan] Univ Wisconsin, Sch Med & Publ Hlth, Dept Neurosurg, Madison, WI 53706 USA. [Wang, Qiwei] Univ Wisconsin, Sch Med & Publ Hlth, Cellular & Mol Pathol Training Program, Madison, WI 53706 USA. [Yang, Sung-Sen; Lin, Shih-Hua] Natl Def Med Ctr, Triserv Gen Hosp, Div Nephrol, Dept Med, Taipei, Taiwan. [Kahle, Kristopher T.] Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. [Kahle, Kristopher T.] Harvard Univ, Sch Med, Boston, MA USA. RP Sun, DD (reprint author), Univ Pittsburgh, Sch Med, Dept Neurol, S-598 S Biomed Sci Tower BST,3500 Terrace St, Pittsburgh, PA 15213 USA. EM sund@upmc.edu RI Kuo, John/D-3561-2013 OI Kuo, John/0000-0001-6809-4806 FU NIH grant [R01NS75995, R01NS38118, R01NS42828, P30 HD03352]; NIH [T32]; AANS-NREF Young Clinician Investigator Award; Loff Memorial Fund; Department of Neurological Surgery Brain Tumor Research Fund FX This work was supported in part by NIH grant R01NS75995, R01NS38118, and R01NS42828 (D. Sun), NIH grant P30 HD03352 (Waisman Center), a NIH T32 grant to University of Wisconsin Stem Cell Training Program (R A. Clark), and the HEADRUSH Brain Tumor Research Professorship, the AANS-NREF Young Clinician Investigator Award, Loff Memorial Fund, and Department of Neurological Surgery Brain Tumor Research Fund (J. S. K). NR 44 TC 17 Z9 18 U1 1 U2 17 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1015-8987 J9 CELL PHYSIOL BIOCHEM JI Cell. Physiol. Biochem. PY 2012 VL 30 IS 1 BP 33 EP 48 DI 10.1159/000339047 PG 16 WC Cell Biology; Physiology SC Cell Biology; Physiology GA 962YA UT WOS:000305585400004 PM 22759954 ER PT B AU McGrath, MM Rubin, MF AF McGrath, Martina M. Rubin, Mario F. BE Chandraker, A Sayegh, MH Singh, AK TI Evaluation of Renal Transplant Candidates SO CORE CONCEPTS IN RENAL TRANSPLANTATION LA English DT Article; Book Chapter DE Age; Malignancy; Infections; Waiting list; Psychosocial issues ID CORONARY-ARTERY-DISEASE; DOBUTAMINE STRESS ECHOCARDIOGRAPHY; ASSOCIATION TASK-FORCE; KIDNEY-TRANSPLANTATION; PRACTICE GUIDELINES; DIABETIC-PATIENTS; PROGNOSTIC VALUE; PANCREAS TRANSPLANTATION; MYOCARDIAL-INFARCTION; HEMODIALYSIS-PATIENTS AB The pretransplant evaluation of kidney transplant candidates is a complex process which is best carried out in the context of a multidisciplinary approach. A given patient's candidacy is determined not only by a careful assessment of the medical/surgical risks but also by a thorough determination of each individual's psychosocial aspects. What follows is our attempt to provide the reader with a series of simple facts which we hope will, in turn, facilitate an understanding of this delicate process. Kidney transplantation is the treatment of choice for most patients with end stage kidney disease (ESKD). There is ample evidence that transplantation is associated with a superior quality and length of life at a lower economic cost. Therefore, appropriate selection of transplant candidates is one of the most important goals of a transplant team. There have been several sets of guidelines produced by experts in the transplantation field to guide the appropriate and timely evaluation of these patients. The goal pretransplant evaluation is to determine that the necessary medical, surgical, and psychosocial conditions are met to derive a maximal benefit from transplantation. C1 [Rubin, Mario F.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [McGrath, Martina M.] Brigham & Womens Hosp, Div Renal, Boston, MA 02115 USA. RP Rubin, MF (reprint author), Massachusetts Gen Hosp, 165 Cambridge St,Suite 302, Boston, MA 02114 USA. EM mfrubin@partners.org NR 62 TC 0 Z9 0 U1 1 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 978-1-4614-0007-3 PY 2012 BP 59 EP 83 DI 10.1007/978-1-4614-0008-0_4 D2 10.1007/978-1-4614-0008-0 PG 25 WC Gastroenterology & Hepatology; Transplantation SC Gastroenterology & Hepatology; Transplantation GA BAC09 UT WOS:000303779000004 ER PT J AU Jubran, A AF Jubran, Amal TI Nurses and ventilators SO CRITICAL CARE LA English DT Editorial Material ID CONTROLLED-TRIAL; OUTCOMES AB In the previous issue of Critical Care, Rose and colleagues report the results of a survey on the frequency with which ICU nurses are involved in decision-making in ventilator management. About 63 to 88% of the decisions were made by nurses in collaboration with physicians, and as much as 68% of ventilator adjustments were performed by nurses independent of physicians. Nurse involvement in decision-making was twice as likely in ICUs that use weaning protocols. The ICU nurse performs many roles, the most important being the continuous observation of a patient. The diversion of a nurse's attention from constant vigilance by performing tasks of no benefit, such as the use of weaning protocols, would be a most unfortunate turn of events. C1 [Jubran, Amal] US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Div Pulm & Crit Care Med, Hines, IL 60141 USA. [Jubran, Amal] Loyola Univ, Med Ctr, Div Pulm & Crit Care Med, Maywood, IL 60153 USA. RP Jubran, A (reprint author), US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Div Pulm & Crit Care Med, 111N,5th Ave & Roosevelt Rd, Hines, IL 60141 USA. EM ajubran@lumc.edu NR 8 TC 2 Z9 2 U1 0 U2 1 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1466-609X J9 CRIT CARE JI Crit. Care PY 2012 VL 16 IS 1 AR 115 DI 10.1186/cc11186 PG 2 WC Critical Care Medicine SC General & Internal Medicine GA 960MU UT WOS:000305393400049 PM 22369739 ER PT J AU Chindelevitch, L Stanley, S Hung, D Regev, A Berger, B AF Chindelevitch, Leonid Stanley, Sarah Hung, Deborah Regev, Aviv Berger, Bonnie TI MetaMerge: scaling up genome-scale metabolic reconstructions with application to Mycobacterium tuberculosis SO GENOME BIOLOGY LA English DT Article ID IDENTIFICATION; CAPABILITIES; YEAST; MODEL AB Reconstructed models of metabolic networks are widely used for studying metabolism in various organisms. Many different reconstructions of the same organism often exist concurrently, forcing researchers to choose one of them at the exclusion of the others. We describe MetaMerge, an algorithm for semi-automatically reconciling a pair of existing metabolic network reconstructions into a single metabolic network model. We use MetaMerge to combine two published metabolic networks for Mycobacterium tuberculosis into a single network, which allows many reactions that could not be active in the individual models to become active, and predicts essential genes with a higher positive predictive value. C1 [Chindelevitch, Leonid; Berger, Bonnie] MIT, Dept Math, Cambridge, MA 02139 USA. [Chindelevitch, Leonid; Berger, Bonnie] MIT, Comp Sci & Artificial Intelligence Lab, Cambridge, MA 02139 USA. [Stanley, Sarah; Hung, Deborah] Massachusetts Gen Hosp, Dept Mol Biol, Simches Res Ctr, Boston, MA 02114 USA. [Stanley, Sarah; Hung, Deborah; Regev, Aviv; Berger, Bonnie] Broad Inst MIT & Harvard, Cambridge, MA 02142 USA. [Regev, Aviv] MIT, Dept Biol, Cambridge, MA 02139 USA. [Regev, Aviv] Howard Hughes Med Inst, Chevy Chase, MD 20815 USA. RP Berger, B (reprint author), MIT, Dept Math, 77 Massachusetts Ave, Cambridge, MA 02139 USA. EM bab@mit.edu FU National Sciences and Engineering Research Council of Canada; Howard Hughes Medical Institute; Burroughs Wellcome Fund; NIH PIONEER; Sloan Fellowship FX The authors would like to thank Marina Druz for providing the IUPAC names and CAS numbers for the metabolites, Jeremy Zucker for providing the KEGG and BioCyc identifiers and Daniel Ziemek for help with the figures. Leonid Chindelevitch was supported by the Postgraduate Award from the National Sciences and Engineering Research Council of Canada. Work was supported by the Howard Hughes Medical Institute, a Career Award at the Scientific Interface from the Burroughs Wellcome Fund, an NIH PIONEER award, and a Sloan Fellowship (AR). NR 20 TC 15 Z9 17 U1 0 U2 4 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1474-7596 J9 GENOME BIOL JI Genome Biol. PY 2012 VL 13 IS 1 AR r6 DI 10.1186/gb-2012-13-1-r6 PG 13 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 960LS UT WOS:000305390300006 PM 22292986 ER PT J AU Mendenhall, EM Bernstein, BE AF Mendenhall, Eric M. Bernstein, Bradley E. TI DNA-protein interactions in high definition SO GENOME BIOLOGY LA English DT Editorial Material AB An elegant, genome-wide approach to define the precise DNA sequences bound by transcription factors has been developed by Rhee and Pugh. C1 [Mendenhall, Eric M.; Bernstein, Bradley E.] Massachusetts Gen Hosp, Howard Hughes Med Inst, Boston, MA 02114 USA. [Mendenhall, Eric M.; Bernstein, Bradley E.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Mendenhall, Eric M.; Bernstein, Bradley E.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Mendenhall, Eric M.; Bernstein, Bradley E.] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. [Mendenhall, Eric M.; Bernstein, Bradley E.] Massachusetts Gen Hosp, Ctr Canc Res, Boston, MA 02114 USA. [Mendenhall, Eric M.; Bernstein, Bradley E.] Broad Inst Harvard & Massachusetts Inst Technol, Cambridge, MA 02139 USA. RP Bernstein, BE (reprint author), Massachusetts Gen Hosp, Howard Hughes Med Inst, Boston, MA 02114 USA. EM Bernstein.Bradley@mgh.harvard.edu OI Mendenhall, Eric/0000-0002-7395-6295 NR 10 TC 1 Z9 1 U1 1 U2 6 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1474-7596 J9 GENOME BIOL JI Genome Biol. PY 2012 VL 13 IS 1 AR 139 DI 10.1186/gb-2012-13-1-139 PG 3 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 960LS UT WOS:000305390300008 PM 22283870 ER PT J AU Zwemer, LM Zak, A Thompson, BR Kirby, A Daly, MJ Chess, A Gimelbrant, AA AF Zwemer, Lillian M. Zak, Alexander Thompson, Benjamin R. Kirby, Andrew Daly, Mark J. Chess, Andrew Gimelbrant, Alexander A. TI Autosomal monoallelic expression in the mouse SO GENOME BIOLOGY LA English DT Article ID ALLELE-SPECIFIC EXPRESSION; CD4(+) T-CELLS; X-CHROMOSOME; GENE-EXPRESSION; INACTIVATION; INTERLEUKIN-2; GENOME AB Background: Random monoallelic expression defines an unusual class of genes displaying random choice for expression between the maternal and paternal alleles. Once established, the allele-specific expression pattern is stably maintained and mitotically inherited. Examples of random monoallelic genes include those found on the X-chromosome and a subset of autosomal genes, which have been most extensively studied in humans. Here, we report a genome-wide analysis of random monoallelic expression in the mouse. We used high density mouse genome polymorphism mapping arrays to assess allele-specific expression in clonal cell lines derived from heterozygous mouse strains. Results: Over 1,300 autosomal genes were assessed for allele-specific expression, and greater than 10% of them showed random monoallelic expression. When comparing mouse and human, the number of autosomal orthologs demonstrating random monoallelic expression in both organisms was greater than would be expected by chance. Random monoallelic expression on the mouse autosomes is broadly similar to that in human cells: it is widespread throughout the genome, lacks chromosome-wide coordination, and varies between cell types. However, for some mouse genes, there appears to be skewing, in some ways resembling skewed X-inactivation, wherein one allele is more frequently active. Conclusions: These data suggest that autosomal random monoallelic expression was present at least as far back as the last common ancestor of rodents and primates. Random monoallelic expression can lead to phenotypic variation beyond the phenotypic variation dictated by genotypic variation. Thus, it is important to take into account random monoallelic expression when examining genotype-phenotype correlation. C1 [Zwemer, Lillian M.; Kirby, Andrew; Daly, Mark J.; Chess, Andrew] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Zak, Alexander; Thompson, Benjamin R.; Gimelbrant, Alexander A.] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. [Chess, Andrew] Mt Sinai Sch Med, Friedman Brain Inst, Dept Dev & Regenerat Biol, Fishberg Dept Neurosci,Dept Genet & Genom Sci, New York, NY 10029 USA. [Gimelbrant, Alexander A.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. RP Chess, A (reprint author), Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. EM andrew.chess@mssm.edu; alexander_gimelbrant@dfci.harvard.edu FU NIH; Barr award; Pew Scholar award FX The authors gratefully acknowledge Aimee Landry for assistance in the maintenance of cell lines, and Jason Alvarez, John Hutchinson, Kathryn Levasseur, and Anwesha Nag for helpful discussions. This work was supported by grants from the NIH to AC and by the Barr award and Pew Scholar award to AAG. NR 22 TC 42 Z9 42 U1 2 U2 14 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1474-7596 J9 GENOME BIOL JI Genome Biol. PY 2012 VL 13 IS 2 AR R10 DI 10.1186/gb-2012-13-2-r10 PG 13 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 960MD UT WOS:000305391700003 PM 22348269 ER PT J AU Patti, JA AF Patti, John A. TI Research, Quality and Safety, Economics: An International Perspective SO JOURNAL OF THE AMERICAN COLLEGE OF RADIOLOGY LA English DT Editorial Material C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Patti, JA (reprint author), Massachusetts Gen Hosp, Dept Radiol, 55 Fruit St,FND 202, Boston, MA 02114 USA. EM jpatti@partners.org 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 1546-1440 J9 J AM COLL RADIOL JI J. Am. Coll. Radiol. PD JAN PY 2012 VL 9 IS 1 BP 1 EP 1 DI 10.1016/j.jacr.2011.11.018 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 961FJ UT WOS:000305449200001 PM 22221625 ER PT J AU Singh, S Kaira, MK Thrall, JH Mahesh, M AF Singh, Sarabjeet Kaira, Mannudeep K. Thrall, James H. Mahesh, Mahadevappa TI Pointers for Optimizing Radiation Dose in Pediatric CT Protocols SO JOURNAL OF THE AMERICAN COLLEGE OF RADIOLOGY LA English DT Editorial Material ID REDUCTION C1 [Singh, Sarabjeet; Kaira, Mannudeep K.; Thrall, James H.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Massachusetts Gen Hosp Imaging, Boston, MA 02114 USA. [Mahesh, Mahadevappa] Johns Hopkins Univ, Russell H Morgan Dept Radiol & Radiol Sci, Baltimore, MD 21287 USA. RP Singh, S (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Massachusetts Gen Hosp Imaging, Boston, MA 02114 USA. EM mmahesh@jhmi.edu NR 11 TC 8 Z9 8 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1546-1440 J9 J AM COLL RADIOL JI J. Am. Coll. Radiol. PD JAN PY 2012 VL 9 IS 1 BP 77 EP 79 DI 10.1016/j.jacr.2011.10.005 PG 3 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 961FJ UT WOS:000305449200017 PM 22221641 ER PT J AU Guiberteau, MJ Brown, ML Oates, ME Thrall, JH AF Guiberteau, Milton J. Brown, Manuel L. Oates, M. Elizabeth Thrall, James H. CA ACR ABR Writing Grp TI Re: "ACR/ABR Clinical Statement on Credentialing and Privileging of Radiologists for Diagnostic Nuclear Medicine, Including Multimodality Hybrid Imaging" Reply SO JOURNAL OF THE AMERICAN COLLEGE OF RADIOLOGY LA English DT Letter C1 [Guiberteau, Milton J.; ACR ABR Writing Grp] St Joseph Med Ctr, Dept Radiol, Houston, TX 77002 USA. [Brown, Manuel L.] Henry Ford Hosp, Dept Diagnost Radiol, Detroit, MI 48202 USA. [Oates, M. Elizabeth] Univ Kentucky, Dept Radiol, Lexington, KY USA. [Thrall, James H.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Guiberteau, MJ (reprint author), St Joseph Med Ctr, Dept Radiol, 1919 LaBranch St, Houston, TX 77002 USA. EM guiberteau@theabr.org NR 1 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1546-1440 J9 J AM COLL RADIOL JI J. Am. Coll. Radiol. PD JAN PY 2012 VL 9 IS 1 BP 83 EP 84 DI 10.1016/j.jacr.2011.11.009 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 961FJ UT WOS:000305449200022 ER PT J AU Thompson, LA Haburcakova, C Gong, WS Lee, DJ Wall, C Merfeld, DM Lewis, RF AF Thompson, Lara A. Haburcakova, Csilla Gong, Wangsong Lee, Daniel J. Wall, Conrad, III Merfeld, Daniel M. Lewis, Richard F. TI Responses evoked by a vestibular implant providing chronic stimulation SO JOURNAL OF VESTIBULAR RESEARCH-EQUILIBRIUM & ORIENTATION LA English DT Article DE Vestibular; vestibular prosthesis; implant; vestibulooccular reflex; psychophysics; balance; posture ID ELECTRICAL-STIMULATION; PROSTHESIS AB Patients with bilateral vestibular loss experience dehabilitating visual, perceptual, and postural difficulties, and an implantable vestibular prosthesis that could improve these symptoms would be of great benefit to these patients. In previous work, we have shown that a one-dimensional, unilateral canal prosthesis can improve the vestibulooccular reflex (VOR) in canal-plugged squirrel monkeys. In addition to the VOR, the potential effects of a vestibular prosthesis on more complex, highly integrative behaviors, such as the perception of head orientation and posture have remained unclear. We tested a one-dimensional, unilateral prosthesis in a rhesus monkey with bilateral vestibular loss and found that chronic electrical stimulation partially restored the compensatory VOR and also that percepts of head orientation relative to gravity were improved. However, the one-dimensional prosthetic stimulation had no clear effect on postural stability during quiet stance, but sway evoked by head-turns was modestly reduced. These results suggest that not only can the implementation of a vestibular prosthesis provide partial restitution of VOR but may also improve perception and posture in the presence of bilateral vestibular hypofunction (BVH). In this review, we provide an overview of our previous and current work directed towards the eventual clinical implementation of an implantable vestibular prosthesis. C1 [Thompson, Lara A.; Haburcakova, Csilla; Gong, Wangsong; Merfeld, Daniel M.; Lewis, Richard F.] Massachusetts Eye & Ear Infirm, Jenks Vestibular Physiol Lab, Boston, MA 02114 USA. [Haburcakova, Csilla; Gong, Wangsong; Lee, Daniel J.; Wall, Conrad, III; Merfeld, Daniel M.; Lewis, Richard F.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. [Lee, Daniel J.; Merfeld, Daniel M.; Lewis, Richard F.] Harvard Univ, Sch Med, Dept Otol & Neurol, Boston, MA USA. [Thompson, Lara A.; Wall, Conrad, III; Merfeld, Daniel M.; Lewis, Richard F.] Harvard Univ, Cambridge, MA 02138 USA. [Thompson, Lara A.; Wall, Conrad, III; Merfeld, Daniel M.; Lewis, Richard F.] MIT, Cambridge, MA 02139 USA. RP Thompson, LA (reprint author), Massachusetts Eye & Ear Infirm, Jenks Vestibular Physiol Lab, 243 Charles St, Boston, MA 02114 USA. EM lthomps@mit.edu FU NIH/NIDCD [DC8362, DC3066, DC008167]; European Commission [225929] FX This work is supported by NIH/NIDCD grants DC8362 and DC3066, DC008167, and European Commission 225929. NR 7 TC 9 Z9 9 U1 0 U2 3 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 0957-4271 J9 J VESTIBUL RES-EQUIL JI J. Vestib. Res.-Equilib. Orientat. PY 2012 VL 22 IS 1 BP 11 EP 15 DI 10.3233/VES-2012-0442 PG 5 WC Neurosciences; Otorhinolaryngology SC Neurosciences & Neurology; Otorhinolaryngology GA 960MJ UT WOS:000305392300003 PM 22699148 ER PT S AU Nappi, JJ Kim, SH Yoshida, H AF Naeppi, Janne J. Kim, Se Hyung Yoshida, Hiroyuki BE VanGinneken, B Novak, CL TI Automated detection of colorectal lesions with dual-energy CT colonography SO MEDICAL IMAGING 2012: COMPUTER-AIDED DIAGNOSIS SE Proceedings of SPIE LA English DT Proceedings Paper CT Conference on Medical Imaging - Computer-Aided Diagnosis CY FEB 07-09, 2012 CL San Diego, CA SP SPIE, Agilent Technol, Diamond SA, DQE Instruments Inc, eMagin, Isuzu Glass Co Ltd, Medtron Inc, Ocean Thin Films Inc DE Computed tomographic colonography; dual energy; polyp detection; false positive reduction; texture analysis; tagging; colon; virtual colonoscopy ID COMPUTED TOMOGRAPHIC COLONOGRAPHY; INITIAL-EXPERIENCE; FALSE POSITIVES; POLYPS AB Conventional single-energy computed tomography colonography (CTC) tends to miss polyps 6 - 9 mm in size and flat lesions. Dual-energy CTC (DE-CTC) provides more complete information about the chemical composition of tissue than does conventional CTC. We developed an automated computer-aided detection (CAD) scheme for detecting colorectal lesions in which dual-energy features were used to identify different bowel materials and their partial-volume artifacts. Based on these features, the dual-energy CAD (DE-CAD) scheme extracted the region of colon by use of a lumen-tracking method, detected lesions by use of volumetric shape features, and reduced false positives by use of a statistical classifier. For validation, 20 patients were prepared for DE-CTC by use of reduced bowel cleansing and orally administered fecal tagging with iodine and/or barium. The DE-CTC was performed in dual positions by use of a dual-energy CT scanner (SOMATOM Definition, Siemens) at 140 kVp and 80 kVp energy levels. The lesions identified by subsequent same-day colonoscopy were correlated with the DE-CTC data. The detection accuracies of the DE-CAD and conventional CAD schemes were compared by use of leave-one-patient-out evaluation and a bootstrap analysis. There were 25 colonoscopy-confirmed lesions: 22 were 6 - 9 mm and 3 were flat lesions >= 10 mm in size. The DE-CAD scheme detected the large flat lesions and 95% of the 6 - 9 mm lesions with 9.9 false positives per patient. The improvement in detection accuracy by the DE-CAD was statistically significant. C1 [Naeppi, Janne J.; Yoshida, Hiroyuki] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Nappi, JJ (reprint author), Massachusetts Gen Hosp, 25 New Chardon St,Suite 400C, Boston, MA 02114 USA. EM jnappi@partners.org; yoshida.hiro@mgh.harvard.edu NR 13 TC 0 Z9 0 U1 0 U2 0 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-0-8194-8964-7 J9 PROC SPIE PY 2012 VL 8315 AR 83150Y DI 10.1117/12.911708 PG 6 WC Optics; Physics, Applied; Radiology, Nuclear Medicine & Medical Imaging SC Optics; Physics; Radiology, Nuclear Medicine & Medical Imaging GA BAT32 UT WOS:000305454600033 ER PT S AU Zhang, D Li, XH Liu, B AF Zhang, Da Li, Xinhua Liu, Bob BE Pelc, NJ Nishikawa, RM Whiting, BR TI Characterization of Adaptive Statistical Iterative Reconstruction (ASiR) in low contrast helical abdominal imaging via a transfer function based method SO MEDICAL IMAGING 2012: PHYSICS OF MEDICAL IMAGING SE Proceedings of SPIE LA English DT Proceedings Paper CT Conference on Medical Imaging - Physics of Medical Imaging CY FEB 05-08, 2012 CL San Diego, CA SP SPIE, Agilent Technol, Diamond SA, DQE Instruments Inc, eMagin, Isuzu Glass Co Ltd, Medtronic, Inc., Ocean Thin Films Inc DE Computed Tomography; Adaptive Statistical Iterative Reconstruction; ASiR; resolution; noise; low contrast imaging ID FILTERED BACK-PROJECTION; RADIATION-DOSE REDUCTION; CORONARY CT ANGIOGRAPHY; QUALITY; CHEST; NOISE AB Since the introduction of ASiR, its potential in noise reduction has been reported in various clinical applications. However, the influence of different scan and reconstruction parameters on the trade off between ASiR's blurring effect and noise reduction in low contrast imaging has not been fully studied. Simple measurements on low contrast images, such as CNR or phantom scores could not explore the nuance nature of this problem. We tackled this topic using a method which compares the performance of ASiR in low contrast helical imaging based on an assumed filter layer on top of the FBP reconstruction. Transfer functions of this filter layer were obtained from the noise power spectra (NPS) of corresponding FBP and ASiR images that share the same scan and reconstruction parameters. 2D transfer functions were calculated as sqrt[NPSASiR(u, v)/NPSFBP(u, v)]. Synthesized ACR phantom images were generated by filtering the FBP images with the transfer functions of specific (FBP, ASiR) pairs, and were compared with the ASiR images. It is shown that the transfer functions could predict the deterministic blurring effect of ASiR on low contrast objects, as well as the degree of noise reductions. Using this method, the influence of dose, scan field of view (SFOV), display field of view (DFOV), ASiR level, and Recon Mode on the behavior of ASiR in low contrast imaging was studied. It was found that ASiR level, dose level, and DFOV play more important roles in determining the behavior of ASiR than the other two parameters. C1 [Zhang, Da; Li, Xinhua; Liu, Bob] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Liu, B (reprint author), Massachusetts Gen Hosp, Dept Radiol, 55 Fruit St, Boston, MA 02114 USA. EM bliu7@bics.bwh.harvard.edu NR 18 TC 0 Z9 0 U1 0 U2 0 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-0-8194-8962-3 J9 PROC SPIE PY 2012 VL 8313 AR 83133S DI 10.1117/12.911082 PG 8 WC Optics; Physics, Applied; Radiology, Nuclear Medicine & Medical Imaging SC Optics; Physics; Radiology, Nuclear Medicine & Medical Imaging GA BAM70 UT WOS:000304768000131 ER PT B AU Ring, D AF Ring, David BE Culp, RW Jacoby, SM TI EXAMINATION OF ELBOW, WRIST, AND HAND FRACTURES SO MUSCULOSKELETAL EXAMINATION OF THE ELBOW, WRIST, AND HAND: MAKING THE COMPLEX SIMPLE SE Musculoskeletal Examination Series LA English DT Article; Book Chapter ID INSTABILITY; SUBLUXATION; DISLOCATION C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Ring, D (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 13 TC 0 Z9 0 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE ROAD, THOROFARE, NJ 08086-9447 USA BN 978-1-55642-918-7 J9 MUSCULOSKELET EXAM PY 2012 BP 274 EP 290 PG 17 WC Orthopedics SC Orthopedics GA BAC22 UT WOS:000303780300013 ER PT S AU McMahon, E Wintermark, P Lahav, A AF McMahon, Erin Wintermark, Pia Lahav, Amir GP Annals NY Acad Sci TI Auditory brain development in premature infants: the importance of early experience SO NEUROSCIENCES AND MUSIC IV: LEARNING AND MEMORY SE Annals of the New York Academy of Sciences LA English DT Article; Proceedings Paper CT Conference on Neurosciences and Music-IV - Learning and Memory CY JUN 09-12, 2011 CL Univ Edinburgh, Edinburgh, SCOTLAND SP Mariani Fdn, Inst Mus Human & Social Dev HO Univ Edinburgh DE auditory; brain; prematurity; newborns; noise; plasticity ID INTENSIVE-CARE-UNIT; KANGAROO MOTHER CARE; FULL-TERM INFANTS; PRETERM INFANTS; SOUND ENVIRONMENT; SENSORY DEPRIVATION; CONTROLLED-TRIAL; FETAL HEARING; MESSENGER-RNA; BIRTH WEIGHTS AB Preterm infants in the neonatal intensive care unit (NICU) often close their eyes in response to bright lights, but they cannot close their ears in response to loud sounds. The sudden transition from the womb to the overly noisy world of the NICU increases the vulnerability of these high-risk newborns. There is a growing concern that the excess noise typically experienced by NICU infants disrupts their growth and development, putting them at risk for hearing, language, and cognitive disabilities. Preterm neonates are especially sensitive to noise because their auditory system is at a critical period of neurodevelopment, and they are no longer shielded by maternal tissue. This paper discusses the developmental milestones of the auditory system and suggests ways to enhance the quality control and type of sounds delivered to NICU infants. We argue that positive auditory experience is essential for early brain maturation and may be a contributing factor for healthy neurodevelopment. Further research is needed to optimize the hospital environment for preterm newborns and to increase their potential to develop into healthy children. C1 [Lahav, Amir] Brigham & Womens Hosp, Neonatal Res Lab, Dept Newborn Med, Boston, MA 02115 USA. [Wintermark, Pia] McGill Univ, Montreal Childrens Hosp, Div Newborn Med, Montreal, PQ H3H 1P3, Canada. [Lahav, Amir] Harvard Univ, Sch Med, Dept Pediat, MassGen Hosp Children, Boston, MA 02115 USA. RP Lahav, A (reprint author), Brigham & Womens Hosp, Neonatal Res Lab, Dept Newborn Med, 75 Francis St, Boston, MA 02115 USA. EM amir@hms.harvard.edu FU Christopher Joseph Concha foundation; Hailey's Hope foundation; Capita foundation; Waterloo foundation; Heather on Earth foundation; Christopher Douglas Hidden Angel foundation; Peter and Elizabeth C. Tower foundation; John Alden Trust; Lifespan Healthcare; Philips Healthcare FX This work was supported by the following foundations: Christopher Joseph Concha, Hailey's Hope, Capita, Waterloo, Heather on Earth, Christopher Douglas Hidden Angel, and Peter and Elizabeth C. Tower, as well as by the John Alden Trust, Lifespan Healthcare, and Philips Healthcare. NR 105 TC 26 Z9 28 U1 3 U2 44 PU BLACKWELL SCIENCE PUBL PI OXFORD PA OSNEY MEAD, OXFORD OX2 0EL, ENGLAND SN 0077-8923 BN 978-1-57331-841-9 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2012 VL 1252 BP 17 EP 24 DI 10.1111/j.1749-6632.2012.06445.x PG 8 WC Multidisciplinary Sciences; Neurosciences; Psychology SC Science & Technology - Other Topics; Neurosciences & Neurology; Psychology GA BAU07 UT WOS:000305518900002 PM 22524335 ER PT S AU Fujioka, T Ween, JE Jamali, S Stuss, DT Ross, B AF Fujioka, Takako Ween, Jon Erik Jamali, Shahab Stuss, Donald T. Ross, Bernhard GP Annals NY Acad Sci TI Changes in neuromagnetic beta-band oscillation after music-supported stroke rehabilitation SO NEUROSCIENCES AND MUSIC IV: LEARNING AND MEMORY SE Annals of the New York Academy of Sciences LA English DT Article; Proceedings Paper CT Conference on Neurosciences and Music-IV - Learning and Memory CY JUN 09-12, 2011 CL Univ Edinburgh, Edinburgh, SCOTLAND SP Mariani Fdn, Inst Mus Human & Social Dev HO Univ Edinburgh DE event-related desynchronization (ERD); stroke rehabilitation; magnetoencephalography (MEG); rhythmic auditory stimulation; timing processing ID MOTOR AREAS; CORTICAL OSCILLATIONS; TACTILE STIMULATION; LONGITUDINAL FMRI; BRAIN; RECOVERY; ACTIVATION; PLASTICITY; THERAPY; ARM AB Precise timing of sound is crucial in music for both performing and listening. Indeed, listening to rhythmic sound sequences activates not only the auditory system but also the sensorimotor system. Previously, we showed the significance of neural beta-band oscillations (15-30 Hz) for the timing processing that involves such auditory-motor coordination. Thus, we hypothesized that motor rehabilitation training incorporating music playing will stimulate and enhance auditory-motor interaction in stroke patients. We examined three chronic patients who received Music-Supported Therapy following the protocols practiced by Schneider. Neuromagnetic beta-band activity was remarkably alike during passive listening to ametronome and during finger tapping, with or without the metronome, for either the paretic or nonparetic hand, suggesting a shared mechanism of the beta modulation. In the listening task, the magnitude of the beta decrease after the tone onset was more pronounced at the posttraining time point and was accompanied by improved arm and hand skills. The present case data give insight into the neural underpinnings of rehabilitation with music making and rhythmic auditory stimulation. C1 [Fujioka, Takako; Stuss, Donald T.; Ross, Bernhard] Baycrest Ctr Geriatr Care, Rotman Res Inst, Toronto, ON M6A 2E1, Canada. [Ween, Jon Erik] Baycrest Ctr Geriatr Care, Stroke & Cognit Clin, Toronto, ON M6A 2E1, Canada. [Ween, Jon Erik] Rockwood Deaconess Med Ctr, Stroke Program, Spokane, WA USA. [Ross, Bernhard] Univ Toronto, Dept Med Biophys, Toronto, ON, Canada. RP Fujioka, T (reprint author), Baycrest Ctr Geriatr Care, Rotman Res Inst, 3560 Bathurst St, Toronto, ON M6A 2E1, Canada. EM tfujioka@rotman-baycrest.on.ca OI Fujioka, Takako/0000-0003-2421-9106 FU Canadian Institutes of Health Research; Centre for Stroke Rehabilitation of the Heart and Stroke Foundation of Ontario; James S. McDonnell Foundation; Canadian Foundation for Innovation FX This work was supported by the Canadian Institutes of Health Research, the Centre for Stroke Rehabilitation of the Heart and Stroke Foundation of Ontario, the James S. McDonnell Foundation, and the Canadian Foundation for Innovation. The authors sincerely thank Eckert Altenmuller and Sabine Schneider for their guidance in MST protocols, Deirdre Dawson and Sara McEwen for their insightful discussions about the study design, Panteha Razavi and Susan Gillingham for their assistance in organizing testing materials and data collection, Michelle Nurwandi for her assistance in behavioral data analysis, Ellen Cohen for her assistance in clinical assessment for the motor skills, and Patricia Van Roon and Brian Fidali for their editorial assistance in the earlier version of the manuscript. NR 72 TC 8 Z9 9 U1 1 U2 15 PU BLACKWELL SCIENCE PUBL PI OXFORD PA OSNEY MEAD, OXFORD OX2 0EL, ENGLAND SN 0077-8923 BN 978-1-57331-841-9 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2012 VL 1252 BP 294 EP 304 DI 10.1111/j.1749-6632.2011.06436.x PG 11 WC Multidisciplinary Sciences; Neurosciences; Psychology SC Science & Technology - Other Topics; Neurosciences & Neurology; Psychology GA BAU07 UT WOS:000305518900038 PM 22524371 ER PT J AU Shazly, TA Latina, MA AF Shazly, Tarek A. Latina, Mark A. TI Use of Processed Pericardium Graft to Plug Patulous Old Sclerostomy Track During Glaucoma Shunt Revision for Exposure SO OPHTHALMIC SURGERY LASERS & IMAGING LA English DT Article ID FOLLOW-UP; TRABECULECTOMY; TUBE AB The authors demonstrate a reproducible technique using processed pericardium to seal sclerostomy track during glaucoma shunt revision. The suggested method involves placement of a wedge-shaped processed pericardial graft into the old sclerostomy tract following tube explantation. The graft is trimmed and sutured to the sclera. The tube is reinserted into a new sclerostomy and then sutured in place and covered in the usual fashion. This method allowed relatively easy treatment of three patients with patulous sclerostomy with necrotic edges. A successful tube revision and repositioning of the tube using this technique was performed on three patients with exposed tubes. The intraocular pressure was between 8 and 12 mm Hg from postoperative day 1. The authors suggest the use of pericardium plug to adequately seal the old sclerostomy track during glaucoma shunt revision. The plug allows tube repositioning at a new site without the need to suture the friable sclerostomy edges. [Ophthalmic Surg Lasers Imaging 2012;43:72-75.] C1 [Shazly, Tarek A.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, Boston, MA USA. [Latina, Mark A.] Reading Hlth Ctr, Reading, MA USA. [Shazly, Tarek A.] Assiut Univ Hosp, Dept Ophthalmol, Assiut, Egypt. RP Latina, MA (reprint author), 20 Pond Meadow Dr,Ste 203, Reading, MA 01867 USA. EM shazlyt@gmail.com OI A Shazly, Tarek/0000-0002-4561-1871 NR 3 TC 2 Z9 2 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 USA SN 1542-8877 J9 OPHTHAL SURG LAS IM JI Ophthalmic Surg. Lasers Imaging PD JAN-FEB PY 2012 VL 43 IS 1 BP 72 EP 75 DI 10.3928/15428877-20111020-01 PG 4 WC Ophthalmology; Surgery SC Ophthalmology; Surgery GA 959VA UT WOS:000305342600012 PM 22045593 ER PT J AU Carbo, AR Blanco, PG Graeme-Cooke, F Misdraji, J Kappler, S Shaffer, K Goldsmith, JD Berzin, T Leffler, D Najarian, R Sepe, P Kaplan, J Pitman, M Goldman, H Pelletier, S Hayward, JN Shields, HM AF Carbo, Alexander R. Blanco, Paola G. Graeme-Cooke, Fiona Misdraji, Joseph Kappler, Steven Shaffer, Kitt Goldsmith, Jeffrey D. Berzin, Tyler Leffler, Daniel Najarian, Robert Sepe, Paul Kaplan, Jennifer Pitman, Martha Goldman, Harvey Pelletier, Stephen Hayward, Jane N. Shields, Helen M. TI Revitalizing pathology laboratories in a gastrointestinal pathophysiology course using multimedia and team-based learning techniques SO PATHOLOGY RESEARCH AND PRACTICE LA English DT Article DE Modified team-based learning; Multimedia presentations; Interdisciplinary curriculum ID EDUCATION; CURRICULUM AB In 2008, we changed the gastrointestinal pathology laboratories in a gastrointestinal pathophysiology course to a more interactive format using modified team-based learning techniques and multimedia presentations. The results were remarkably positive and can be used as a model for pathology laboratory improvement in any organ system. Over a two-year period,. engaging and interactive pathology laboratories were designed. The initial restructuring of the laboratories included new case material, Digital Atlas of Video Education Project videos, animations and overlays. Subsequent changes included USMLE board-style quizzes at the beginning of each laboratory, with individual readiness assessment testing and group readiness assessment testing, incorporation of a clinician as a co-teacher and role playing for the student groups. Student responses for pathology laboratory contribution to learning improved significantly compared to baseline. Increased voluntary attendance at pathology laboratories was observed. Spontaneous student comments noted the positive impact of the laboratories on their learning. Pathology laboratory innovations, including modified team-based learning techniques with individual and group self-assessment quizzes, multimedia presentations, and paired teaching by a pathologist and clinical gastroenterologist led to improvement in student perceptions of pathology laboratory contributions to their learning and better pathology faculty evaluations. These changes can be universally applied to other pathology laboratories to improve student satisfaction. (C) 2012 Elsevier GmbH. All rights reserved. C1 [Shields, Helen M.] Beth Israel Deaconess Med Ctr, Div Gastroenterol, Dept Med, Boston, MA 02215 USA. [Carbo, Alexander R.; Blanco, Paola G.; Graeme-Cooke, Fiona; Misdraji, Joseph; Kappler, Steven; Goldsmith, Jeffrey D.; Berzin, Tyler; Leffler, Daniel; Najarian, Robert; Sepe, Paul; Kaplan, Jennifer; Pitman, Martha; Goldman, Harvey; Pelletier, Stephen; Shields, Helen M.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Graeme-Cooke, Fiona; Misdraji, Joseph; Pitman, Martha] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Goldsmith, Jeffrey D.; Najarian, Robert; Kaplan, Jennifer; Goldman, Harvey] Beth Israel Deaconess Med Ctr, Dept Pathol, Boston, MA 02215 USA. [Shaffer, Kitt] Boston Univ, Dept Radiol, Sch Med, Boston, MA 02215 USA. RP Shields, HM (reprint author), Beth Israel Deaconess Med Ctr, Div Gastroenterol, Dept Med, 330 Brookline Ave, Boston, MA 02215 USA. EM hshields@bidmc.harvard.edu RI Herring, Anna/L-7859-2014; OI Berzin, Tyler/0000-0002-4364-6210; Shaffer, Kitt/0000-0001-6488-6988 NR 8 TC 4 Z9 4 U1 0 U2 5 PU ELSEVIER GMBH, URBAN & FISCHER VERLAG PI JENA PA OFFICE JENA, P O BOX 100537, 07705 JENA, GERMANY SN 0344-0338 J9 PATHOL RES PRACT JI Pathol. Res. Pract. PY 2012 VL 208 IS 5 BP 300 EP 305 DI 10.1016/j.prp.2012.02.010 PG 6 WC Pathology SC Pathology GA 963XZ UT WOS:000305659600006 PM 22464153 ER PT S AU Yonker, LM Fracchia, MS AF Yonker, Lael M. Fracchia, M. Shannon BE Hartnick, CJ Hansen, MC Gallagher, TQ TI Flexible Bronchoscopy SO PEDIATRIC AIRWAY SURGERY SE Advances in Oto-Rhino-Laryngology LA English DT Article; Book Chapter AB Flexible bronchoscopy is an important procedure for evaluating the pediatric airway, allowing a dynamic view from the trachea through the lower bronchi. The flexible bronchoscope offers greater maneuverability than the rigid bronchoscope and may be done in conjunction with other procedures, such as bronchoalveolar lavage, transbronchial biopsy, endobronchial ultrasound, electrocautery or laser treatments. Common indications for flexible bronchoscopy include recurrent croup or pneumonia, aspiration, foreign body and chronic cough. Although bronchospasm, transient fever, infection and pneumothorax are rare complications of flexible bronchoscopy, these risks are minimized with careful technique and an ongoing dialogue with the anesthesiologist. Flexible bronchoscopy is an important tool in the diagnosis, monitoring and therapy of certain pulmonary diseases and should be considered in the management of carefully selected pediatric patients. Copyright (C) 2012 S. Karger AG, Basel C1 [Yonker, Lael M.; Fracchia, M. Shannon] Massachusetts Gen Hosp, Pediat Pulm Dept, Boston, MA 02114 USA. [Fracchia, M. Shannon] Massachusetts Eye & Ear Infirm, Pediat Airway Clin, Boston, MA 02114 USA. RP Yonker, LM (reprint author), Massachusetts Gen Hosp, Pediat Pulm Dept, 275 Cambridge St, Boston, MA 02114 USA. EM lyonker@partners.org NR 4 TC 2 Z9 2 U1 0 U2 1 PU KARGER PI BASEL PA POSTFACH, CH-4009 BASEL, SWITZERLAND SN 0065-3071 BN 978-3-8055-9932-0 J9 ADV OTO-RHINO-LARYNG JI Adv.Otorhinolaryngol. PY 2012 VL 73 BP 12 EP 18 PG 7 WC Otorhinolaryngology SC Otorhinolaryngology GA BAE11 UT WOS:000303897800002 PM 22472222 ER PT S AU Gallagher, TQ Hartnick, CJ AF Gallagher, Thomas Q. Hartnick, Christopher J. BE Hartnick, CJ Hansen, MC Gallagher, TQ TI Direct Laryngoscopy and Rigid Bronchoscopy SO PEDIATRIC AIRWAY SURGERY SE Advances in Oto-Rhino-Laryngology LA English DT Article; Book Chapter ID ENDOSCOPY AB Laryngoscopy and rigid bronchoscopy represent a necessary tool in the otolaryngologist's arsenal. The advancement in designing smaller and more versatile laryngeal equipment and fiber-optic telescopes as well as the increasingly higher resolution of still and video imagery have allowed otolaryngologists to better diagnose and treat many airway lesions. This chapter describes the basic equipment necessary as well step-by-step description of the technique to perform rigid airway endoscopy. C1 [Hartnick, Christopher J.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Massachusetts Eye & Ear Infirm, Boston, MA 02116 USA. [Gallagher, Thomas Q.] USN, LCDR, MC, Dept Otolaryngol,Med Ctr Portsmouth, Portsmouth, VA USA. RP Hartnick, CJ (reprint author), Harvard Univ, Sch Med, Dept Otol & Laryngol, Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02116 USA. EM christopher_hartnick@meei.harvard.edu; christopher_hartnick@meei.harvard.edu NR 2 TC 2 Z9 2 U1 0 U2 0 PU KARGER PI BASEL PA POSTFACH, CH-4009 BASEL, SWITZERLAND SN 0065-3071 BN 978-3-8055-9932-0 J9 ADV OTO-RHINO-LARYNG JI Adv.Otorhinolaryngol. PY 2012 VL 73 BP 19 EP 25 PG 7 WC Otorhinolaryngology SC Otorhinolaryngology GA BAE11 UT WOS:000303897800003 PM 22472223 ER PT S AU Gallagher, TQ Hartnick, CJ AF Gallagher, Thomas Q. Hartnick, Christopher J. BE Hartnick, CJ Hansen, MC Gallagher, TQ TI Pediatric Tracheotomy SO PEDIATRIC AIRWAY SURGERY SE Advances in Oto-Rhino-Laryngology LA English DT Article; Book Chapter ID INFANT TRACHEOTOMY; COMPLICATIONS; TRACHEOSTOMY AB The procedure of tracheotomy dates back to ancient times. Its use has been adapted in the neonatal and pediatric population over the past half-century. Despite being a life-saving measure, tracheotomy-related mortality rates range from 0.5 to 3.6%, and this procedure is not without significant and sometimes frequent complications. Techniques regarding pediatric tracheotomy vary from surgeon to surgeon and include orientation of skin incision, removal of subcutaneous tissue, orientation of tracheotomy, maturation and stay sutures, as well postoperative care and surveillance. In this chapter, the authors detail their technique for tracheotomy. Surgical pearls for success are highlighted. C1 [Hartnick, Christopher J.] Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Dept Otol & Laryngol, Boston, MA 02116 USA. [Gallagher, Thomas Q.] USN, LCDR, MC, Dept Otolaryngol,Med Ctr Portsmouth, Portsmouth, VA USA. RP Hartnick, CJ (reprint author), Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Dept Otol & Laryngol, 243 Charles St, Boston, MA 02116 USA. EM christopher_hartnick@meei.harvard.edu; christopher_hartnick@meei.harvard.edu NR 8 TC 5 Z9 5 U1 0 U2 1 PU KARGER PI BASEL PA POSTFACH, CH-4009 BASEL, SWITZERLAND SN 0065-3071 BN 978-3-8055-9932-0 J9 ADV OTO-RHINO-LARYNG JI Adv.Otorhinolaryngol. PY 2012 VL 73 BP 26 EP 30 PG 5 WC Otorhinolaryngology SC Otorhinolaryngology GA BAE11 UT WOS:000303897800004 PM 22472224 ER PT S AU Gallagher, TQ Hartnick, CJ AF Gallagher, Thomas Q. Hartnick, Christopher J. BE Hartnick, CJ Hansen, MC Gallagher, TQ TI Laryngotracheal Reconstruction SO PEDIATRIC AIRWAY SURGERY SE Advances in Oto-Rhino-Laryngology LA English DT Article; Book Chapter ID SUBGLOTTIC STENOSIS AB Laryngotracheal reconstruction (LTR) along with cricotracheal resection and thyrotracheal anastomosis has become the standard of care for symptomatic subglottic stenosis in the pediatric age group. Success rates in achieving decannulation or avoiding tracheotomy approach 90%. Fearon and Cotton introduced pediatric LTR in 1972 using cartilage interposition grafting. The procedure has evolved to include a variety of techniques for expanding the laryngotracheal complex to obtain a stable airway of sufficient size for respiration. In this chapter, the authors will describe their single and double-stage technique for LTR highlighting surgical pearls necessary for success. C1 [Hartnick, Christopher J.] Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Dept Otol & Laryngol, Boston, MA 02116 USA. [Gallagher, Thomas Q.] USN, LCDR, MC, Dept Otolaryngol,Med Ctr Portsmouth, Portsmouth, VA USA. RP Hartnick, CJ (reprint author), Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Dept Otol & Laryngol, 243 Charles St, Boston, MA 02116 USA. EM christopher_hartnick@meei.harvard.edu; christopher_hartnick@meei.harvard.edu NR 4 TC 4 Z9 5 U1 0 U2 0 PU KARGER PI BASEL PA POSTFACH, CH-4009 BASEL, SWITZERLAND SN 0065-3071 BN 978-3-8055-9932-0 J9 ADV OTO-RHINO-LARYNG JI Adv.Otorhinolaryngol. PY 2012 VL 73 BP 31 EP 38 PG 8 WC Otorhinolaryngology SC Otorhinolaryngology GA BAE11 UT WOS:000303897800005 PM 22472225 ER PT S AU Gallagher, TQ Hartnick, CJ AF Gallagher, Thomas Q. Hartnick, Christopher J. BE Hartnick, CJ Hansen, MC Gallagher, TQ TI Costal Cartilage Harvest SO PEDIATRIC AIRWAY SURGERY SE Advances in Oto-Rhino-Laryngology LA English DT Article; Book Chapter AB Cartilage interposition grafting for treatment of subglottic stenosis was pioneered by Fearon and Cotton in 1972. Costal cartilage is the preferred source for graft material in most cases. In this section, the authors highlight the surgical technique for cartilage graft harvest with discussion of surgical pearls necessary for success. C1 [Hartnick, Christopher J.] Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Dept Otol & Laryngol, Boston, MA 02116 USA. [Gallagher, Thomas Q.] USN, LCDR, MC, Dept Otolaryngol,Med Ctr Portsmouth, Portsmouth, VA USA. RP Hartnick, CJ (reprint author), Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Dept Otol & Laryngol, 243 Charles St, Boston, MA 02116 USA. EM christopher_hartnick@meei.harvard.edu; christopher_hartnick@meei.harvard.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU KARGER PI BASEL PA POSTFACH, CH-4009 BASEL, SWITZERLAND SN 0065-3071 BN 978-3-8055-9932-0 J9 ADV OTO-RHINO-LARYNG JI Adv.Otorhinolaryngol. PY 2012 VL 73 BP 39 EP 41 PG 3 WC Otorhinolaryngology SC Otorhinolaryngology GA BAE11 UT WOS:000303897800006 PM 22472226 ER PT S AU Gallagher, TQ Hartnick, CJ AF Gallagher, Thomas Q. Hartnick, Christopher J. BE Hartnick, CJ Hansen, MC Gallagher, TQ TI Cricotracheal Resection and Thryotracheal Anastomosis SO PEDIATRIC AIRWAY SURGERY SE Advances in Oto-Rhino-Laryngology LA English DT Article; Book Chapter ID PEDIATRIC SUBGLOTTIC STENOSIS; LARYNGOTRACHEAL STENOSIS; CHILDREN; LARYNGEAL AB Cricotracheal resection and thryotracheal anastomosis along with laryngotracheal reconstruction have become the standard of care for symptomatic subglottic stenosis in the pediatric age g roup with decannulation rates approaching 90%. The procedure is ideal for children with subglottic stenosis several millimeters distal to the true vocal cords and can be extended to include costal interposition grafting if necessary. In this chapter, the authors describe the surgical techniques necessary for successful resection and reanastonnosis. C1 [Gallagher, Thomas Q.] USN, LCDR, MC, Med Ctr Portsmouth,Dept Otolaryngol, Portsmouth, VA 23708 USA. [Hartnick, Christopher J.] Massachusetts Eye & Ear Infirm, Dept Otol & Laryngol, Boston, MA 02114 USA. RP Gallagher, TQ (reprint author), USN, LCDR, MC, Med Ctr Portsmouth,Dept Otolaryngol, Bldg 3,4th Floor,620 John Paul Jones Circle, Portsmouth, VA 23708 USA. EM thomasqgallagher@yahoo.com; thomasqgallagher@yahoo.com NR 13 TC 1 Z9 1 U1 0 U2 0 PU KARGER PI BASEL PA POSTFACH, CH-4009 BASEL, SWITZERLAND SN 0065-3071 BN 978-3-8055-9932-0 J9 ADV OTO-RHINO-LARYNG JI Adv.Otorhinolaryngol. PY 2012 VL 73 BP 42 EP 49 PG 8 WC Otorhinolaryngology SC Otorhinolaryngology GA BAE11 UT WOS:000303897800007 PM 22472227 ER PT S AU Gallagher, TQ Hartnick, CJ AF Gallagher, Thomas Q. Hartnick, Christopher J. BE Hartnick, CJ Hansen, MC Gallagher, TQ TI Tracheal Resection and Reanastomosis SO PEDIATRIC AIRWAY SURGERY SE Advances in Oto-Rhino-Laryngology LA English DT Article; Book Chapter AB Isolated short segment tracheal stenosis occurs in a relatively rare subpopulation of patients with laryngotracheal stenosis. Etiologies include both acquired and congenital, the most common being the acquired type. Management options include observation, endoscopic balloon dilation with or without CO2 laser, stent placement and open airway surgery. In this chapter, we will discuss tracheal resection and reanastomosis with emphasis on surgical pearls for success. C1 [Hartnick, Christopher J.] Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Dept Otol & Laryngol, Boston, MA 02116 USA. [Gallagher, Thomas Q.] USN, LCDR, MC, Dept Otolaryngol,Med Ctr Portsmouth, Portsmouth, VA USA. RP Hartnick, CJ (reprint author), Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Dept Otol & Laryngol, 243 Charles St, Boston, MA 02116 USA. EM christopher_hartnick@meei.harvard.edu; christopher_hartnick@meei.harvard.edu NR 3 TC 3 Z9 4 U1 0 U2 0 PU KARGER PI BASEL PA POSTFACH, CH-4009 BASEL, SWITZERLAND SN 0065-3071 BN 978-3-8055-9932-0 J9 ADV OTO-RHINO-LARYNG JI Adv.Otorhinolaryngol. PY 2012 VL 73 BP 50 EP 57 PG 8 WC Otorhinolaryngology SC Otorhinolaryngology GA BAE11 UT WOS:000303897800008 PM 22472228 ER PT S AU Gallagher, TQ Hartnick, CJ AF Gallagher, Thomas Q. Hartnick, Christopher J. BE Hartnick, CJ Hansen, MC Gallagher, TQ TI Slide Tracheoplasty SO PEDIATRIC AIRWAY SURGERY SE Advances in Oto-Rhino-Laryngology LA English DT Article; Book Chapter ID CONGENITAL TRACHEAL STENOSIS; MANAGEMENT; GROWTH AB Slide tracheoplasty, first described in 1989, has become the procedure of choice for long segment tracheal stenosis and complete tracheal rings. Although a challenging surgery with higher mortality than other open airway procedures, this technique offers a successful alternative for parents who just a couple decades ago had no reasonable surgical option. We describe the management of long segment tracheal stenosis using the slide tracheoplasty highlighting the surgical pearls necessary for success. C1 [Hartnick, Christopher J.] Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Dept Otol & Laryngol, Boston, MA 02116 USA. [Gallagher, Thomas Q.] USN, LCDR, MC, Dept Otolaryngol,Med Ctr Portsmouth, Portsmouth, VA USA. RP Hartnick, CJ (reprint author), Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Dept Otol & Laryngol, 243 Charles St, Boston, MA 02116 USA. EM christopher_hartnick@meei.harvard.edu; christopher_hartnick@meei.harvard.edu NR 6 TC 0 Z9 0 U1 1 U2 1 PU KARGER PI BASEL PA POSTFACH, CH-4009 BASEL, SWITZERLAND SN 0065-3071 BN 978-3-8055-9932-0 J9 ADV OTO-RHINO-LARYNG JI Adv.Otorhinolaryngol. PY 2012 VL 73 BP 58 EP 62 PG 5 WC Otorhinolaryngology SC Otorhinolaryngology GA BAE11 UT WOS:000303897800009 PM 22472229 ER PT S AU Gallagher, TQ Hartnick, CJ AF Gallagher, Thomas Q. Hartnick, Christopher J. BE Hartnick, CJ Hansen, MC Gallagher, TQ TI Suprastomal Granuloma SO PEDIATRIC AIRWAY SURGERY SE Advances in Oto-Rhino-Laryngology LA English DT Article; Book Chapter ID TRACHEOTOMY; CHILDREN AB Suprastomal granuloma is one of the most common sequelae of pediatric tracheotomy. Numerous different techniques have been described for their removal including endoscopic and open procedures. The following chapter discusses the intraoperative techniques for open removal of suprastomal granuloma in infants. C1 [Hartnick, Christopher J.] Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Dept Otol & Laryngol, Boston, MA 02116 USA. [Gallagher, Thomas Q.] USN, LCDR, MC, Dept Otolaryngol,Med Ctr Portsmouth, Portsmouth, VA USA. RP Hartnick, CJ (reprint author), Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Dept Otol & Laryngol, 243 Charles St, Boston, MA 02116 USA. EM christopher_hartnick@meei.harvard.edu; christopher_hartnick@meei.harvard.edu NR 5 TC 0 Z9 0 U1 0 U2 1 PU KARGER PI BASEL PA POSTFACH, CH-4009 BASEL, SWITZERLAND SN 0065-3071 BN 978-3-8055-9932-0 J9 ADV OTO-RHINO-LARYNG JI Adv.Otorhinolaryngol. PY 2012 VL 73 BP 63 EP 65 PG 3 WC Otorhinolaryngology SC Otorhinolaryngology GA BAE11 UT WOS:000303897800010 PM 22472230 ER PT S AU Gallagher, TQ Hartnick, CJ AF Gallagher, Thomas Q. Hartnick, Christopher J. BE Hartnick, CJ Hansen, MC Gallagher, TQ TI Thyroglossal Duct Cyst Excision SO PEDIATRIC AIRWAY SURGERY SE Advances in Oto-Rhino-Laryngology LA English DT Article; Book Chapter ID MANAGEMENT AB Thyroglossal duct cysts (TGDCs) are the most common congenital anomaly of the neck. The most common presentation of TGDCs is a firm, midline mass. The Sistrunk procedure is the recommended treatment for TGDCs. Based on anatomic and embryologic study, Dr. Sistrunk recommended removal of not only the cyst and central portion of the hyoid bone, but also a central core of deep tongue musculature. By doing so, the rate of recurrence is decreased from approximately 50 to 3-5%. In this chapter, the authors will describe the Sistrunk procedure step by step including surgical pearls for success. C1 [Hartnick, Christopher J.] Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Dept Otol & Laryngol, Boston, MA 02116 USA. [Gallagher, Thomas Q.] USN, LCDR, MC, Dept Otolaryngol,Med Ctr Portsmouth, Portsmouth, VA USA. RP Hartnick, CJ (reprint author), Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Dept Otol & Laryngol, 243 Charles St, Boston, MA 02116 USA. EM christopher_hartnick@meei.harvard.edu; christopher_hartnick@meei.harvard.edu NR 5 TC 2 Z9 4 U1 0 U2 0 PU KARGER PI BASEL PA POSTFACH, CH-4009 BASEL, SWITZERLAND SN 0065-3071 BN 978-3-8055-9932-0 J9 ADV OTO-RHINO-LARYNG JI Adv.Otorhinolaryngol. PY 2012 VL 73 BP 66 EP 69 PG 4 WC Otorhinolaryngology SC Otorhinolaryngology GA BAE11 UT WOS:000303897800011 PM 22472231 ER PT S AU Gallagher, TQ Hartnick, CJ AF Gallagher, Thomas Q. Hartnick, Christopher J. BE Hartnick, CJ Hansen, MC Gallagher, TQ TI Bilateral Submandibular Gland Excision and Parotid Duct Ligation SO PEDIATRIC AIRWAY SURGERY SE Advances in Oto-Rhino-Laryngology LA English DT Article; Book Chapter ID CEREBRAL-PALSY; SIALORRHEA; CHILDREN; MANAGEMENT; RESECTION AB Sialorrhea affects a significant number of children with cerebral palsy and other neuromuscular disorders. It can lead not only to social embarrassment but also to severe medical issues including chronic aspiration. There are numerous medical and surgical options, which include oral medications and transdermal patches, botulinum injection, and various forms of surgical ligation or excision of the major salivary glands. In this chapter, the authors describe the surgical management of sialorrhea, highlighting surgical pearls necessary for success. C1 [Gallagher, Thomas Q.] USN, LCDR, MC, Med Ctr Portsmouth,Dept Otolaryngol, Portsmouth, VA 23708 USA. [Hartnick, Christopher J.] Massachusetts Eye & Ear Infirm, Dept Otol & Laryngol, Boston, MA 02114 USA. RP Gallagher, TQ (reprint author), USN, LCDR, MC, Med Ctr Portsmouth,Dept Otolaryngol, Bldg 3,4th Floor,620 John Paul Jones Circle, Portsmouth, VA 23708 USA. EM thomasqgallagher@yahoo.com; thomasqgallagher@yahoo.com NR 9 TC 0 Z9 0 U1 0 U2 0 PU KARGER PI BASEL PA POSTFACH, CH-4009 BASEL, SWITZERLAND SN 0065-3071 BN 978-3-8055-9932-0 J9 ADV OTO-RHINO-LARYNG JI Adv.Otorhinolaryngol. PY 2012 VL 73 BP 70 EP 75 PG 6 WC Otorhinolaryngology SC Otorhinolaryngology GA BAE11 UT WOS:000303897800012 PM 22472232 ER PT S AU Gallagher, TQ Hartnick, CJ AF Gallagher, Thomas Q. Hartnick, Christopher J. BE Hartnick, CJ Hansen, MC Gallagher, TQ TI Tracheocutaneous Fistula Closure SO PEDIATRIC AIRWAY SURGERY SE Advances in Oto-Rhino-Laryngology LA English DT Article; Book Chapter ID STOMA AB Tracheocutaneous fistula (TCF) is one of the recognized sequelae of tracheotomy in the pediatric age group. Persistent TCF can cause considerable morbidity due to recurrent aspiration, and subsequent respiratory infection, difficulty in phonation, ineffective cough, skin irritation, cosmesis, social acceptance, and intolerance to submersion. Methods of TCF closure remain controversial and vary based on the otolaryngologist's preference. The authors' choice is fistulectomy with primary closure in layers as this definitively removes the fistula and provides the patient with a good cosmetic result without the need for any significant postoperative wound care. The following chapter describes our techniques as well as surgical pearls for success. C1 [Hartnick, Christopher J.] Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Dept Otol & Laryngol, Boston, MA 02116 USA. [Gallagher, Thomas Q.] USN, LCDR, MC, Dept Otolaryngol,Med Ctr Portsmouth, Portsmouth, VA USA. RP Hartnick, CJ (reprint author), Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Dept Otol & Laryngol, 243 Charles St, Boston, MA 02116 USA. EM christopher_hartnick@meei.harvard.edu; christopher_hartnick@meei.harvard.edu NR 9 TC 4 Z9 6 U1 0 U2 0 PU KARGER PI BASEL PA POSTFACH, CH-4009 BASEL, SWITZERLAND SN 0065-3071 BN 978-3-8055-9932-0 J9 ADV OTO-RHINO-LARYNG JI Adv.Otorhinolaryngol. PY 2012 VL 73 BP 76 EP 79 PG 4 WC Otorhinolaryngology SC Otorhinolaryngology GA BAE11 UT WOS:000303897800013 PM 22472233 ER PT S AU Maturo, SC Hartnick, CJ AF Maturo, Stephen C. Hartnick, Christopher J. BE Hartnick, CJ Hansen, MC Gallagher, TQ TI Pediatric Laryngeal Electromyography SO PEDIATRIC AIRWAY SURGERY SE Advances in Oto-Rhino-Laryngology LA English DT Article; Book Chapter ID VOCAL FOLD PARALYSIS; CORD PARALYSIS; THYROARYTENOID MUSCLES; CANINE MODEL; CHILDREN; IMMOBILITY AB Vocal fold immobility (VFI) is a challenging management issue in pediatric otolaryngology. VFI is most commonly distinguished between unilateral (UVFI) and bilateral (BVFI) dysfunction. UVFI and BVFI are different pathophysiologic and clinical entities with distinct symptoms and etiologies. It has been generally accepted in the adult literature to wait at least 1 year prior to carrying out more permanent type procedures for VFI. This period has been extended out even further in children as the literature has suggested that vocal fold function may return many years later. Unfortunately, there is no simple test or procedure to help predict return of vocal fold function. In adult patients LEMG has been used to help guide management decisions, but it has not been widely investigated in children. In this chapter the authors describe a LEMG technique that has been a useful adjunct in managing children with VFI. C1 [Hartnick, Christopher J.] Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Dept Otol & Laryngol, Boston, MA 02116 USA. [Maturo, Stephen C.] San Antonio Mil Med Ctr, Dept Otolaryngol, Ft Sam Houston, TX USA. RP Hartnick, CJ (reprint author), Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Dept Otol & Laryngol, 243 Charles St, Boston, MA 02116 USA. EM christopher_hartnick@meei.harvard.edu; christopher_hartnick@meei.harvard.edu NR 17 TC 2 Z9 2 U1 0 U2 0 PU KARGER PI BASEL PA POSTFACH, CH-4009 BASEL, SWITZERLAND SN 0065-3071 BN 978-3-8055-9932-0 J9 ADV OTO-RHINO-LARYNG JI Adv.Otorhinolaryngol. PY 2012 VL 73 BP 86 EP 89 PG 4 WC Otorhinolaryngology SC Otorhinolaryngology GA BAE11 UT WOS:000303897800015 PM 22472235 ER PT S AU Maturo, SC Hartnick, CJ AF Maturo, Stephen C. Hartnick, Christopher J. BE Hartnick, CJ Hansen, MC Gallagher, TQ TI Juvenile-Onset Recurrent Respiratory Papillomatosis SO PEDIATRIC AIRWAY SURGERY SE Advances in Oto-Rhino-Laryngology LA English DT Article; Book Chapter ID INTRALESIONAL CIDOFOVIR; CHILDREN; INDOLE-3-CARBINOL; INJECTIONS; LARYNGEAL; EXPOSURE AB Juvenile-onset recurrent respiratory papillomatosis, caused by the human papilloma virus, is the most common benign neoplasm of the larynx in children. Recurrent respiratory papillomatosis is relatively rare, but it can have a significant impact on afflicted children and their family's quality of life as dysphonia and multiple surgical procedures are hallmarks of this disease. The current standard of care is surgical therapy with a goal of complete papilloma removal and preservation of normal structures. The technique in this atlas combines both the microdebrider and the pulse KTP laser. The microdebrider allows for rapid removal of bulky lesions without the risk of thermal injury, yet it cannot provide precise removal in areas such as the anterior commissure and ventricle. The pulse KTP laser allows for removal of sessile lesions and in sensitive areas such as the vocal folds. The authors describe this technique as well as discuss adjuvant therapies and pearls for success. C1 [Hartnick, Christopher J.] Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Dept Otol & Laryngol, Boston, MA 02116 USA. [Maturo, Stephen C.] San Antonio Mil Med Ctr, Dept Otolaryngol, Ft Sam Houston, TX USA. RP Hartnick, CJ (reprint author), Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Dept Otol & Laryngol, 243 Charles St, Boston, MA 02116 USA. EM christopher_hartnick@meei.harvard.edu; christopher_hartnick@meei.harvard.edu NR 13 TC 1 Z9 2 U1 0 U2 2 PU KARGER PI BASEL PA POSTFACH, CH-4009 BASEL, SWITZERLAND SN 0065-3071 BN 978-3-8055-9932-0 J9 ADV OTO-RHINO-LARYNG JI Adv.Otorhinolaryngol. PY 2012 VL 73 BP 105 EP 108 PG 4 WC Otorhinolaryngology SC Otorhinolaryngology GA BAE11 UT WOS:000303897800019 PM 22472239 ER PT S AU Maturo, SC Hartnick, CJ AF Maturo, Stephen C. Hartnick, Christopher J. BE Hartnick, CJ Hansen, MC Gallagher, TQ TI Pediatric Lingual Tonsillectomy SO PEDIATRIC AIRWAY SURGERY SE Advances in Oto-Rhino-Laryngology LA English DT Article; Book Chapter AB Tonsillectomy and adenoidectomy are an effective surgical treatment of pediatric obstructive sleep apnea; however, up to 20% of these patients can have persistent disease. In this select patient population, the lingual tonsil may be an occult source of obstruction. Lingual tonsillectomy can be a challenging procedure due to poor access and visualization, airway edema, postoperative pain and hemostasis during tissue removal. In this chapter, we describe our preferred technique for lingual tonsillectomy including surgical pearls for success. C1 [Hartnick, Christopher J.] Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Dept Otol & Laryngol, Boston, MA 02116 USA. [Maturo, Stephen C.] San Antonio Mil Med Ctr, Dept Otolaryngol, Ft Sam Houston, TX USA. RP Hartnick, CJ (reprint author), Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Dept Otol & Laryngol, 243 Charles St, Boston, MA 02116 USA. EM christopher_hartnick@meei.harvard.edu; christopher_hartnick@meei.harvard.edu NR 4 TC 2 Z9 2 U1 1 U2 2 PU KARGER PI BASEL PA POSTFACH, CH-4009 BASEL, SWITZERLAND SN 0065-3071 BN 978-3-8055-9932-0 J9 ADV OTO-RHINO-LARYNG JI Adv.Otorhinolaryngol. PY 2012 VL 73 BP 109 EP 111 PG 3 WC Otorhinolaryngology SC Otorhinolaryngology GA BAE11 UT WOS:000303897800020 PM 22472240 ER PT S AU Maturo, SC Hartnick, CJ AF Maturo, Stephen C. Hartnick, Christopher J. BE Hartnick, CJ Hansen, MC Gallagher, TQ TI Pediatric Airway Balloon Dilation SO PEDIATRIC AIRWAY SURGERY SE Advances in Oto-Rhino-Laryngology LA English DT Article; Book Chapter ID SUBGLOTTIC STENOSIS AB Over the past decade, there has also been renewed interest in serial dilatation for the management of subglottic and tracheal stenosis with the advent of new technologies such as airway balloons designed for the pediatric airway. In this chapter, the authors describe the technique of application of airway balloons as a useful adjunct for management of airway lesions. C1 [Hartnick, Christopher J.] Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Dept Otol & Laryngol, Boston, MA 02116 USA. [Maturo, Stephen C.] San Antonio Mil Med Ctr, Dept Otolaryngol, Ft Sam Houston, TX USA. RP Hartnick, CJ (reprint author), Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Dept Otol & Laryngol, 243 Charles St, Boston, MA 02116 USA. EM christopher_hartnick@meei.harvard.edu; christopher_hartnick@meei.harvard.edu NR 6 TC 4 Z9 4 U1 0 U2 2 PU KARGER PI BASEL PA POSTFACH, CH-4009 BASEL, SWITZERLAND SN 0065-3071 BN 978-3-8055-9932-0 J9 ADV OTO-RHINO-LARYNG JI Adv.Otorhinolaryngol. PY 2012 VL 73 BP 112 EP 115 PG 4 WC Otorhinolaryngology SC Otorhinolaryngology GA BAE11 UT WOS:000303897800021 PM 22472241 ER PT S AU Gallagher, TQ Hartnick, CJ AF Gallagher, Thomas Q. Hartnick, Christopher J. BE Hartnick, CJ Hansen, MC Gallagher, TQ TI Endoscopic Choanal Atresia Repair SO PEDIATRIC AIRWAY SURGERY SE Advances in Oto-Rhino-Laryngology LA English DT Article; Book Chapter ID HYPERTHYROIDISM AB Congenital choanal atresia (CA) is relatively rare, with an incidence of 1 in 7,000 births with a majority being the mixed bony-membranous type. There are 5 described methods of CA repair: transpalatal, transnasal, sublabial-transnasal, transantral, and transseptal approaches. Transpalatal and transnasal have been the most popular in the last several decades with transnasal becoming the preferred technique with the advent of endoscopic instruments and techniques. In this chapter, the authors seek to describe their techniques for endoscopic transnasal repair of CA including surgical pearls for success. C1 [Hartnick, Christopher J.] Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Dept Otol & Laryngol, Boston, MA 02116 USA. [Gallagher, Thomas Q.] USN, LCDR, MC, Dept Otolaryngol,Med Ctr Portsmouth, Portsmouth, VA USA. RP Hartnick, CJ (reprint author), Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Dept Otol & Laryngol, 243 Charles St, Boston, MA 02116 USA. EM christopher_hartnick@meei.harvard.edu; christopher_hartnick@meei.harvard.edu NR 6 TC 1 Z9 1 U1 0 U2 1 PU KARGER PI BASEL PA POSTFACH, CH-4009 BASEL, SWITZERLAND SN 0065-3071 BN 978-3-8055-9932-0 J9 ADV OTO-RHINO-LARYNG JI Adv.Otorhinolaryngol. PY 2012 VL 73 BP 127 EP 131 PG 5 WC Otorhinolaryngology SC Otorhinolaryngology GA BAE11 UT WOS:000303897800024 PM 22472244 ER PT S AU Bruch, JM Setlur, J AF Bruch, Jean M. Setlur, Jennifer BE Hartnick, CJ Hansen, MC Gallagher, TQ TI Pediatric Sialendoscopy SO PEDIATRIC AIRWAY SURGERY SE Advances in Oto-Rhino-Laryngology LA English DT Article; Book Chapter ID JUVENILE RECURRENT PAROTITIS; SIALOLITHIASIS AB Sialendoscopy was introduced in the early 1990s as a minimally invasive alternative to standard methods for diagnosis and treatment of inflammatory and obstructive salivary gland disease. The technique was pioneered in adults; however, advances in instrumentation have allowed this to be adapted to the smaller salivary ductal anatomy found in the pediatric population. In this chapter, the technique of sialendoscopy for parotid and submandibular glands is described. Copyright (C) 2012 S. Karger AG, Basel C1 [Bruch, Jean M.; Setlur, Jennifer] Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. RP Bruch, JM (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA. EM jean_bruch@meei.harvard.edu NR 12 TC 3 Z9 3 U1 0 U2 0 PU KARGER PI BASEL PA POSTFACH, CH-4009 BASEL, SWITZERLAND SN 0065-3071 BN 978-3-8055-9932-0 J9 ADV OTO-RHINO-LARYNG JI Adv.Otorhinolaryngol. PY 2012 VL 73 BP 149 EP 152 PG 4 WC Otorhinolaryngology SC Otorhinolaryngology GA BAE11 UT WOS:000303897800028 PM 22472248 ER PT J AU Fang, MA Heiney, C Yentes, JM Harada, ND Masih, S Perell-Gerson, KL AF Fang, Meika A. Heiney, Constance Yentes, Jennifer M. Harada, Nancy D. Masih, Sulabha Perell-Gerson, Karen L. TI Clinical and Spatiotemporal Gait Effects of Canes in Hip Osteoarthritis SO PM&R LA English DT Article ID KNEE OSTEOARTHRITIS; ASSISTIVE DEVICES; MUSCLE MOMENTS; PAIN; EPIDEMIOLOGY; PREVENTION; MANAGEMENT; WALKERS; WALKING AB Objective: To investigate the effects of cane use on spatiotemporal gait parameters, pain, and function in adults with hip osteoarthritis (OA). Design: Prospective observational study. Setting: An academic tertiary Veterans Affairs Healthcare Center. Participants: Thirteen adults with symptomatic hip OA and 13 healthy adults. Methods: We undertook gait analysis in all subjects with an optoelectronic camera system. Pain, stiffness, and physical function in subjects with hip OA were assessed with the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). Main Outcome Measurements: Baseline spatiotemporal measures of unaided gait were obtained for healthy subjects. Baseline and 4-week spatiotemporal gait parameters were assessed for hip OA subjects while they walked with and without a cane. Participants with hip OA completed the WOMAC at baseline and after 4 weeks of cane use. Results: At baseline when walking unaided, the subjects with hip OA (age range 60-75 years) had a significantly slower gait velocity, shorter affected limb stride length, and longer double-stance time compared with healthy control subjects. When walking with a cane, they had a reduction in gait velocity (P < .05) caused by a decrease in cadence (P < .05) compared with walking unaided. After 4 weeks of cane use, the participants with hip OA demonstrated significant improvements in gait velocity (P < .05) and double-stance time (P < .05) when walking with a cane in comparison with baseline data. There was no improvement in pain and function after 4 weeks of cane use, a period in which only approximately 60% of the hip OA subjects used the cane 6 or more times per week. Conclusions: Initial use of a cane led to decreased gait velocity and cadence in people with hip OA compared with walking unaided. This difference in gait velocity diminished after they practiced walking with the cane. Inconsistent use of the cane may have contributed to the lack of improvement in the subjects' hip OA pain and function. PM R 2012;4:30-36 C1 [Fang, Meika A.; Heiney, Constance; Harada, Nancy D.; Masih, Sulabha; Perell-Gerson, Karen L.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Fang, Meika A.; Harada, Nancy D.; Masih, Sulabha] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Yentes, Jennifer M.] Univ Nebraska, Nebraska Biomech Core Facil, Omaha, NE 68182 USA. [Perell-Gerson, Karen L.] Georgia Gwinnett Coll, Sch Sci & Technol, Lawrenceville, GA USA. RP Fang, MA (reprint author), Rheumatol Sect 111J,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM meika.fang@med.va.gov OI Yentes, Jennifer/0000-0001-6550-7759 FU Southern California Arthritis Foundation FX This work was supported by an Innovative Research Grant from the Southern California Arthritis Foundation. NR 36 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 1934-1482 J9 PM&R JI PM&R PD JAN PY 2012 VL 4 IS 1 BP 30 EP 36 DI 10.1016/j.pmrj.2011.08.534 PG 7 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 961BF UT WOS:000305438200006 PM 22088853 ER PT B AU Sundt, TM AF Sundt, Thoralf M., III BE Machiraju, VR Schaff, H Svensson, LG TI Reoperation Following Homograft Aortic Valve Replacement SO REDO CARDIAC SURGERY IN ADULTS, SECOND EDITION LA English DT Article; Book Chapter C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Sundt, TM (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. EM tsundt@partners.org NR 10 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 978-1-4614-1325-7 PY 2012 BP 133 EP 139 DI 10.1007/978-1-4614-1326-4_16 D2 10.1007/978-1-4614-1326-4 PG 7 WC Cardiac & Cardiovascular Systems; Surgery SC Cardiovascular System & Cardiology; Surgery GA BAC18 UT WOS:000303779900016 ER PT B AU Weir, GC Bonner-Weir, S Sharma, A AF Weir, Gordon C. Bonner-Weir, Susan Sharma, Arun BE Skyler, JS TI Regulation of Insulin Secretion and Islet Cell Function SO ATLAS OF DIABETES, FOURTH EDITION LA English DT Article; Book Chapter ID CHRONIC HYPERGLYCEMIA; GLUCOSE-TOLERANCE; DIABETES-MELLITUS; BETA-CELLS; PANCREAS; RAT; PROGENITORS; DYSFUNCTION; PROGRESSION; LANGERHANS C1 [Weir, Gordon C.; Bonner-Weir, Susan; Sharma, Arun] Harvard Univ, Sch Med, Joslin Diabet Ctr, Islet Cell & Regenerat Biol Dept, Boston, MA 02115 USA. RP Weir, GC (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, Islet Cell & Regenerat Biol Dept, Boston, MA 02115 USA. OI Bonner-Weir, Susan/0000-0003-4682-0656 NR 40 TC 0 Z9 0 U1 1 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 978-1-4614-1027-0 PY 2012 BP 1 EP 17 DI 10.1007/978-1-4614-1028-7_1 D2 10.1007/978-1-4614-1028-7 PG 17 WC Primary Health Care SC General & Internal Medicine GA BAB34 UT WOS:000303688400001 ER PT B AU Aiello, LP Silva, PS Sun, JK AF Aiello, Lloyd Paul Silva, Paolo S. Sun, Jennifer K. BE Skyler, JS TI Eye Complications of Diabetes SO ATLAS OF DIABETES, FOURTH EDITION LA English DT Article; Book Chapter ID ENDOTHELIAL GROWTH-FACTOR; MACULAR EDEMA; INTRAVITREAL TRIAMCINOLONE; RETINAL NEOVASCULARIZATION; COST-EFFECTIVENESS; RETINOPATHY; MELLITUS; TRIAL; PROGRESSION; PHOTOCOAGULATION C1 [Aiello, Lloyd Paul; Sun, Jennifer K.] Harvard Univ, Sch Med, Dept Ophthalmol, Beetham Eye Inst, Boston, MA 02114 USA. [Aiello, Lloyd Paul] Harvard Dept Ophthalmol, Ctr Excellence, Boston, MA USA. [Aiello, Lloyd Paul] Brigham & Womens Hosp, Boston, MA 02115 USA. [Aiello, Lloyd Paul; Sun, Jennifer K.] Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA. [Silva, Paolo S.] Joslin Diabet Ctr, Beetham Eye Inst, Boston, MA 02215 USA. [Sun, Jennifer K.] Harvard Univ, Eye Res Sect, Boston, MA USA. RP Aiello, LP (reprint author), Harvard Univ, Sch Med, Dept Ophthalmol, Beetham Eye Inst, Boston, MA 02114 USA. NR 52 TC 0 Z9 0 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 978-1-4614-1027-0 PY 2012 BP 249 EP 275 DI 10.1007/978-1-4614-1028-7_12 D2 10.1007/978-1-4614-1028-7 PG 27 WC Primary Health Care SC General & Internal Medicine GA BAB34 UT WOS:000303688400012 ER PT B AU Stanton, RC AF Stanton, Robert C. BE Skyler, JS TI Diabetes and the Kidney SO ATLAS OF DIABETES, FOURTH EDITION LA English DT Article; Book Chapter ID STAGE RENAL-DISEASE; OXIDATIVE STRESS; CARDIOVASCULAR-DISEASE; INTENSIVE TREATMENT; OVERT NEPHROPATHY; BLOOD-PRESSURE; UNITED-STATES; END-PRODUCTS; COMPLICATIONS; PROGRESSION C1 [Stanton, Robert C.] Joslin Diabet Ctr, Renal Sect, Boston, MA 02215 USA. [Stanton, Robert C.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. RP Stanton, RC (reprint author), Joslin Diabet Ctr, Renal Sect, Boston, MA 02215 USA. NR 61 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 978-1-4614-1027-0 PY 2012 BP 277 EP 294 DI 10.1007/978-1-4614-1028-7_13 D2 10.1007/978-1-4614-1028-7 PG 18 WC Primary Health Care SC General & Internal Medicine GA BAB34 UT WOS:000303688400013 ER PT B AU Snapper, SB Nguyen, DD AF Snapper, Scott B. Nguyen, Deanna D. BE Baumgart, DC TI Immunobiology of T Cells in Inflammatory Bowel Disease SO CROHN'S DISEASE AND ULCERATIVE COLITIS: FROM EPIDEMIOLOGY AND IMMUNOBIOLOGY TO A RATIONAL DIAGNOSTIC AND THERAPEUTIC APPROACH LA English DT Article; Book Chapter DE CD4+T cells; CD8+T cells; TCR gamma delta cells; Regulatory T cells; Effector T cells; T-cell plasticity; Tr1 cells; Th3 cells; Th1 cells; Th2 cells; Th17 cells; iT(R)35; Inducible regulatory T cells; iTregs; Naturally occurring regulatory T cells; nTregs; NK-T cells; Foxp3; Scurfy mice; IPEX; IL-10; TGF-beta; IL-35; IL-5; IL-13; IL-17; CCR9; alpha 4 beta 7; Natalizumab; Vedolizumab ID CHRONIC INTESTINAL INFLAMMATION; IMMUNOLOGICAL SELF-TOLERANCE; TRANSCRIPTION FACTOR FOXP3; ULCERATIVE-COLITIS; CROHNS-DISEASE; AUTOIMMUNE ENCEPHALOMYELITIS; LAMINA PROPRIA; CUTTING EDGE; HUMANIZED ANTIBODY; ADOPTIVE TRANSFER C1 [Snapper, Scott B.] Childrens Hosp, Boston, MA 02115 USA. [Snapper, Scott B.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Nguyen, Deanna D.] Massachusetts Gen Hosp, Dept Med, Gastrointestinal Unit, Boston, MA 02114 USA. RP Snapper, SB (reprint author), Childrens Hosp, 300 Longwood Ave, Boston, MA 02115 USA. EM scott.snapper@childrens.harvard.edu NR 63 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 978-1-4614-0997-7 PY 2012 BP 151 EP 159 DI 10.1007/978-1-4614-0998-4_11 D2 10.1007/978-1-4614-0998-4 PG 9 WC Gastroenterology & Hepatology; Medicine, General & Internal SC Gastroenterology & Hepatology; General & Internal Medicine GA BAD42 UT WOS:000303840400011 ER PT B AU Mizoguchi, A Bhan, AK AF Mizoguchi, Atsushi Bhan, Atul K. BE Baumgart, DC TI Immunobiology of B Cells in Inflammatory Bowel Disease SO CROHN'S DISEASE AND ULCERATIVE COLITIS: FROM EPIDEMIOLOGY AND IMMUNOBIOLOGY TO A RATIONAL DIAGNOSTIC AND THERAPEUTIC APPROACH LA English DT Article; Book Chapter DE Autoantibodies; Breg; Colitis; IL-10; IL-12; Inflammatory bowel disease; Regulatory B cells; T-cell receptor knockout mice ID ALPHA MUTANT MICE; REGULATORY T-CELLS; GROWTH-FACTOR-BETA; ULCERATIVE-COLITIS; INTESTINAL INFLAMMATION; MURINE MODEL; CROHNS-DISEASE; DEFICIENT MICE; ANIMAL-MODELS; LYMPHOCYTES C1 [Mizoguchi, Atsushi; Bhan, Atul K.] Harvard Univ, Massachusetts Gen Hosp, Dept Pathol, Immunopathol Unit, Boston, MA 02114 USA. RP Bhan, AK (reprint author), Harvard Univ, Massachusetts Gen Hosp, Dept Pathol, Immunopathol Unit, Warren 501,55 Fruit St, Boston, MA 02114 USA. EM abhan@partners.org NR 66 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 978-1-4614-0997-7 PY 2012 BP 161 EP 168 DI 10.1007/978-1-4614-0998-4_12 D2 10.1007/978-1-4614-0998-4 PG 8 WC Gastroenterology & Hepatology; Medicine, General & Internal SC Gastroenterology & Hepatology; General & Internal Medicine GA BAD42 UT WOS:000303840400012 ER PT B AU Liu, SH Ren, SP Howell, PM Riker, AI AF Liu, Suhu Ren, Suping Howell, Paul M., Jr. Riker, Adam I. BE Murphy, MJ TI Epigenetic Biomarkers in Melanoma SO DIAGNOSTIC AND PROGNOSTIC BIOMARKERS AND THERAPEUTIC TARGETS IN MELANOMA SE Current Clinical Pathology LA English DT Article; Book Chapter ID HISTONE DEACETYLASE INHIBITORS; NF-KAPPA-B; ISLAND METHYLATOR PHENOTYPE; HUMAN CUTANEOUS MELANOMA; HUMAN CANCER-CELLS; MODIFICATIONS PREDICT PROGNOSIS; PROMOTER DNA METHYLATION; HUMAN LUNG CANCERS; PHASE-I TRIAL; MALIGNANT-MELANOMA C1 [Riker, Adam I.] Ochsner Hlth Syst, Ochsner Canc Inst, Ochsner Med Ctr, Dept Surg, New Orleans, LA 70121 USA. [Liu, Suhu] Harvard Univ, Dana Farber Canc Inst, Boston, MA 02115 USA. [Ren, Suping; Howell, Paul M., Jr.] Univ S Alabama, Mitchell Canc Inst, Mobile, AL 36688 USA. RP Riker, AI (reprint author), Ochsner Hlth Syst, Ochsner Canc Inst, Ochsner Med Ctr, Dept Surg, New Orleans, LA 70121 USA. EM ariker1234@gmail.com NR 198 TC 0 Z9 0 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA BN 978-1-60761-432-6 J9 CURR CLIN PATHOL PY 2012 BP 89 EP 112 DI 10.1007/978-1-60761-433-3_8 D2 10.1007/978-1-60762-433-3 PG 24 WC Oncology; Dermatology; Pathology SC Oncology; Dermatology; Pathology GA BAF46 UT WOS:000304018300008 ER PT S AU Sackstein, R AF Sackstein, Robert GP Annals NY Acad Sci TI Engineering cellular trafficking via glycosyltransferase- programmed stereosubstitution SO GLYCOBIOLOGY OF THE IMMUNE RESPONSE SE Annals of the New York Academy of Sciences LA English DT Article; Book Chapter DE HCELL; GPS; mesenchymal stem cell; hematopoietic stem cell; cell migration ID L-SELECTIN LIGAND; P-SELECTIN; IN-VIVO; LEUKOCYTE ADHESION; HEMATOPOIETIC STEM; PROGENITOR CELLS; BONE-MARROW; EXPRESSION; HCELL; NEUTROPHILS AB The proximate hurdle for cell trafficking to any anatomic site is the initial attachment of circulating cells to target tissue endothelium with sufficient strength to overcome prevailing forces of blood flow. E-selectin, an endothelial molecule that is inducibly expressed at all sites of inflammation, is a potent effector of this primary braking process. This molecule is a member of a family of C-type lectins known as selectins that bind sialofucosylated glycans displayed on either a protein (i.e., glycoprotein) or lipid (i.e., glycolipid) scaffold. On human cells, the predominant E-selectin ligand is a specialized glycoform of CD44 known as hematopoietic cell E-/L-selectin ligand (HCELL). This review focuses on the biology of HCELL/E-selectin interactions in cell migration, and discusses the utility and applicability of glycosyltransferase-programmed stereosubstitution (GPS) for glycoengineering HCELL expression. Without compromising cell viability or native phenotype, this exoglycosylation technology literally "sweetens" CD44, licensing E-selectin-dependent vascular delivery for all cell-based therapeutics. C1 [Sackstein, Robert] Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. [Sackstein, Robert] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med,Dept Med Oncol,Dana Farber Canc Inst, Boston, MA 02115 USA. RP Sackstein, R (reprint author), Harvard Inst Med, 77 Ave Louis Pasteur,Room 671, Boston, MA 02115 USA. EM Rsackstein@rics.bwh.harvard.edu FU NCI NIH HHS [R01 CA121335-03, R01 CA121335-05, R01 CA121335-04, R01 CA121335, R01 CA121335-02, R01 CA121335-01A1]; NHLBI NIH HHS [R01 HL073714-01, R01 HL060528-06A1, P01 HL107146, R01 HL060528-07, R01 HL060528-08, R01 HL073714-02, R01 HL073714-03, R01 HL060528-04, P01 HL107146-01, R01HL60528, R01 HL060528, R01 HL073714-05, R01 HL060528-10, R01 HL073714-04, R01 HL073714, R01 HL060528-09, R01HL73714, R01 HL073714-08, R01 HL073714-07, R01 HL060528-05, R01 HL073714-06] NR 31 TC 7 Z9 7 U1 0 U2 4 PU BLACKWELL SCIENCE PUBL PI OXFORD PA OSNEY MEAD, OXFORD OX2 0EL, ENGLAND SN 0077-8923 BN 978-1-57331-839-6 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2012 VL 1253 BP 193 EP 200 DI 10.1111/j.1749-6632.2011.06421.x PG 8 WC Biochemistry & Molecular Biology; Immunology; Multidisciplinary Sciences SC Biochemistry & Molecular Biology; Immunology; Science & Technology - Other Topics GA BAU74 UT WOS:000305567700017 PM 22352800 ER PT J AU Suvak, MK Brogan, LA Shipherd, JC AF Suvak, Michael K. Brogan, Leah A. Shipherd, Jillian C. TI PREDICTORS OF SEXUAL FUNCTIONING IN A SAMPLE OF US MARINES: AN 11-YEAR FOLLOW-UP STUDY SO INTERNATIONAL JOURNAL OF SEXUAL HEALTH LA English DT Article DE Sexual functioning; military personnel; veterans; trauma; mental health ID POSTTRAUMATIC-STRESS-DISORDER; VETERANS-ADMINISTRATION OUTPATIENTS; COMMON MENTAL-DISORDERS; GULF-WAR VETERANS; NEGATIVE AFFECT; EXTERNALIZING SPECTRUM; PERSONALITY-DISORDER; ANTISOCIAL-BEHAVIOR; SOCIAL-ADJUSTMENT; MILITARY SERVICE AB We examined predictors of sexual functioning in male and female U. S. Marines (n = 589) assessed longitudinally for approximately 11 years. Multiple domains of sexual functioning (dysfunctional sexual behaviors, sexual frequency, sexual problems, and sexual satisfaction) were assessed at the 11-year follow-up assessment (T5). T5 depressive symptoms emerged as the most robust predictor of all domains of sexual functioning. Different patterns of correlates were associated with the different domains of sexual functioning-a finding that highlights the importance of considering the multidimensional nature of human sexuality. In addition, several significant gender x predictor interactions indicated differential relationships between predictors and sexual functioning outcomes for men and women. In particular, concurrent physical health and mental health were more strongly related to sexual functioning for women compared with men. We discuss how findings of the current study can contribute to the development of theories that can better capture the complexity of human sexuality, and we suggest ways that the current findings can inform mental health practitioners working with veterans and military personnel. C1 [Suvak, Michael K.] Suffolk Univ, Dept Psychol, Boston, MA 02114 USA. [Shipherd, Jillian C.] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02118 USA. [Suvak, Michael K.; Brogan, Leah A.; Shipherd, Jillian C.] VA Boston Healthcare Syst, Womens Hlth Sci Div, Natl Ctr PTSD, Boston, MA USA. RP Suvak, MK (reprint author), Suffolk Univ, Dept Psychol, 41 Temple St, Boston, MA 02114 USA. EM msuvak@suffolk.edu NR 61 TC 5 Z9 5 U1 1 U2 6 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 1931-7611 J9 INT J SEX HEALTH JI Int. J. Sex. Health PY 2012 VL 24 IS 1 SI SI BP 26 EP 44 DI 10.1080/19317611.2011.640387 PG 19 WC Psychology, Clinical; Public, Environmental & Occupational Health; Social Sciences, Interdisciplinary SC Psychology; Public, Environmental & Occupational Health; Social Sciences - Other Topics GA 956BS UT WOS:000305065400004 ER PT J AU Shipherd, JC Mizock, L Maguen, S Green, KE AF Shipherd, Jillian C. Mizock, Lauren Maguen, Shira Green, Kelly E. TI MALE-TO-FEMALE TRANSGENDER VETERANS AND VA HEALTH CARE UTILIZATION SO INTERNATIONAL JOURNAL OF SEXUAL HEALTH LA English DT Article DE Transgender; transsexual; gender; veteran; service utilization; barriers to care AB This study examined rates of military veteran status in an American male-to-female transgender community sample (n = 141). Thirty percent were veterans (n = 43), a rate that is triple the proportion of veteran status noted in the general population (10.1%). Among the veteran subsample, we examined health care utilization, including Veterans Health Administration (VA), health, and barriers to care. Use of VA services was higher among transgender veterans (transvets) than published rates of VA use in the general population of veterans (annual 6.2% to 15.8%), with 16.3% of all transvets seeking some VA care in the past 6-months. The most common physical health problems treated at the VA in the past year were high cholesterol, blood pressure, and vision problems. Irrespective of VA use, the majority of transvets reported getting routine health care (88.4%), and their physical health ratings were commensurate with population norms. Mental health services (e. g., depression, posttraumatic stress disorder, and gender identity counseling) were also utilized (9.3% VA, 25.6% non-VA) at levels consistent with the relatively low mental health functioning scores in this sample (SF-12 = 32.6, SD = 8.3). Barriers to care were endorsed more for medical than mental health treatment. In particular, transvets were concerned about medical providers' reactions to their gender identity or sexual orientation. Given elevated rates of transvets in this community sample and reported barriers to care, culturally sensitive treatment is a priority for transvets in both VA and non-VA health care systems. C1 [Shipherd, Jillian C.; Green, Kelly E.] VA Boston Healthcare Syst, Dept Vet Affairs, Boston, MA USA. [Shipherd, Jillian C.] Natl Ctr PTSD, Womens Hlth Sci Div, Boston, MA USA. [Shipherd, Jillian C.] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02118 USA. [Mizock, Lauren] Boston Univ, Ctr Psychiat Rehabil, Boston, MA 02215 USA. [Maguen, Shira] San Francisco VA Med Ctr, Dept Vet Affairs, San Francisco, CA USA. [Maguen, Shira] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA USA. [Green, Kelly E.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. RP Shipherd, JC (reprint author), VA Boston Healthcare Syst 116B 3, Dept Vet Affairs, 150 S Huntington Ave, Boston, MA 02130 USA. EM Jillian.shipherd@va.gov NR 21 TC 18 Z9 18 U1 1 U2 5 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 1931-7611 J9 INT J SEX HEALTH JI Int. J. Sex. Health PY 2012 VL 24 IS 1 SI SI BP 78 EP 87 DI 10.1080/19317611.2011.639440 PG 10 WC Psychology, Clinical; Public, Environmental & Occupational Health; Social Sciences, Interdisciplinary SC Psychology; Public, Environmental & Occupational Health; Social Sciences - Other Topics GA 956BS UT WOS:000305065400007 ER PT J AU Desseilles, M Chang, TN Piguet, C Bertschy, G Dayer, AG AF Desseilles, Martin Chang, Trina Piguet, Camille Bertschy, Gilles Dayer, Alexandre G. TI A Three-Dimensional Model of Thoughts: Insight into Depression SO PSYCHOPATHOLOGY LA English DT Review DE Thoughts; Cognition; Mood; Depression; Creativity ID MOOD INDUCTION PROCEDURE; BIPOLAR DISORDER; POSITIVE AFFECT; HEDONIC TONE; CREATIVITY; NETWORK; METAANALYSIS; REAPPRAISAL; ACTIVATION; DREAMS AB Thought processing and mood regulation are closely linked, but existing classifications of mood disorders fail to recognize the complex interplay between these two clinical dimensions. Furthermore, existing classifications fail to account for the possibility that depression might be associated with an increased frequency of self-referential thoughts that could in some circumstances be related to creativity processes. Based on recent evidence from clinical phenomenology, experimental psychology and affective neuroscience, we propose a novel comprehensive theoretical framework that incorporates thought processing and emotional valence. This new taxonomy provides insights into the clinical understanding of the spectrum of mood disorders and accounts for the possibility of increased creativity in altered mood states. Copyright (C) 2012 S. Karger AG, Basel C1 [Desseilles, Martin] Univ Liege, Cyclotron Res Ctr, Liege, Belgium. [Desseilles, Martin; Chang, Trina] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Depress Clin & Res Program, Boston, MA USA. [Bertschy, Gilles] Univ Strasbourg, Dept Psychiat, Strasbourg, France. [Bertschy, Gilles] Univ Hosp Strasbourg, INSERM, U666, Strasbourg, France. [Desseilles, Martin; Piguet, Camille; Dayer, Alexandre G.] Univ Hosp Geneva, Dept Basic Neurosci, Univ Med Ctr, Geneva, Switzerland. [Desseilles, Martin; Piguet, Camille; Dayer, Alexandre G.] Univ Hosp Geneva, Dept Mental Hlth & Psychiat, Geneva, Switzerland. RP Desseilles, M (reprint author), Univ Liege B30, Cyclotron Res Ctr, 8,Allee 6 Aout, BE-4000 Liege, Belgium. EM m.desseilles@ulg.ac.be OI Dayer, Alexandre/0000-0002-4490-9780 FU FNRS-FRS; Fonds National de la Recherche Scientifique (FNRS - Switzerland); Jean and Madeleine Vachoux Foundation; Fonds Leon Fredericq; Wallonie-Bruxelles International; Belgian American Educational Foundation FX Funding for this study was provided by an FNRS-FRS grant to M.D. C.P. and A.G.D. are supported by the Fonds National de la Recherche Scientifique (FNRS - Switzerland). Additional funds come from the Jean and Madeleine Vachoux Foundation, the Fonds Leon Fredericq, Wallonie-Bruxelles International, and the Belgian American Educational Foundation. The sponsors had no further role in study design; in the collection, analysis and interpretation of data; in the writing of the report, and in the decision to submit the paper for publication. NR 50 TC 3 Z9 3 U1 0 U2 13 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0254-4962 J9 PSYCHOPATHOLOGY JI Psychopathology PY 2012 VL 45 IS 4 BP 203 EP 214 DI 10.1159/000335073 PG 12 WC Psychiatry SC Psychiatry GA 960IA UT WOS:000305380000001 PM 22627507 ER PT J AU Farabaugh, A Bitran, S Nyer, M Holt, DJ Pedrelli, P Shyu, I Hollon, SD Zisook, S Baer, L Busse, W Petersen, TJ Pender, M Tucker, DD Fava, M AF Farabaugh, Amy Bitran, Stella Nyer, Maren Holt, Daphne J. Pedrelli, Paola Shyu, Irene Hollon, Steven D. Zisook, Sidney Baer, Lee Busse, Wilma Petersen, Timothy J. Pender, Maribeth Tucker, Dorothy D. Fava, Maurizio TI Depression and Suicidal Ideation in College Students SO PSYCHOPATHOLOGY LA English DT Article DE Suicide; College students; Screening; Depression; Suicidal ideation ID HOPELESSNESS; BEHAVIORS AB Background/Aims: Suicide is one of the leading causes of death in college students and is often associated with depression. The aim of this study was to assess the rates of suicidal ideation (SI) on college campuses and to identify its correlates. Methods: On-campus depression screening sessions were conducted at 3 universities (n = 898; 55% female; mean age 20.07 +/- 1.85 years). Participants completed the Beck Depression Inventory (BDI; mean +/- SD of total score = 6.27 +/- 6.31) and other measures. Eighty-four students endorsed a '1' on the BDI suicidality item, suggesting thoughts of suicide. Results: Results showed that students with greater depression severity, higher levels of hopelessness, and poorer quality of life were more likely to endorse SI. Conclusion: Factors associated with SI highlighted in this study may aid in the identification of college students at risk for suicide. Copyright (C) 2012 S. Karger AG, Basel C1 [Farabaugh, Amy; Bitran, Stella; Nyer, Maren; Holt, Daphne J.; Pedrelli, Paola; Shyu, Irene; Baer, Lee; Petersen, Timothy J.; Pender, Maribeth; Fava, Maurizio] Suffolk Univ, Depress Clin & Res Program, Massachusetts Gen Hosp, Boston, MA 02114 USA. [Busse, Wilma] Suffolk Univ, Counseling Ctr, Boston, MA 02114 USA. [Hollon, Steven D.; Tucker, Dorothy D.] Vanderbilt Univ, Dept Psychol, Nashville, TN 37240 USA. [Zisook, Sidney] Univ Calif San Diego, Dept Psychiat, San Diego, CA 92103 USA. RP Farabaugh, A (reprint author), Suffolk Univ, Depress Clin & Res Program, Massachusetts Gen Hosp, 50 Staniford St,Suite 401, Boston, MA 02114 USA. EM afarabaugh@partners.org FU Jed Foundation FX Supported by a grant from The Jed Foundation. NR 27 TC 19 Z9 20 U1 2 U2 22 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0254-4962 J9 PSYCHOPATHOLOGY JI Psychopathology PY 2012 VL 45 IS 4 BP 228 EP 234 DI 10.1159/000331598 PG 7 WC Psychiatry SC Psychiatry GA 960IA UT WOS:000305380000004 PM 22627683 ER PT J AU Trevisi, M Talamo, A Bandinelli, PL Ducci, G Kotzalidis, GD Santucci, C Manfredi, G Girardi, N Tatarelli, R AF Trevisi, Manuela Talamo, Alessandra Bandinelli, Pier Luca Ducci, Giuseppe Kotzalidis, Giorgio D. Santucci, Chiara Manfredi, Giovanni Girardi, Nicoletta Tatarelli, Roberto TI Insight and Awareness as Related to Psychopathology and Cognition SO PSYCHOPATHOLOGY LA English DT Article DE Insight (illness awareness); Schizophrenia; Bipolar disorder; Depression, unipolar; Wisconsin Card Sorting Test ID BIPOLAR-I DISORDER; CHRONIC-SCHIZOPHRENIA; DEPRESSIVE-DISORDERS; CLINICAL-PSYCHIATRY; TREATMENT ADHERENCE; VERBAL MEMORY; RATING-SCALE; PSYCHOSIS; ILLNESS; PSYCHOEDUCATION AB Background: Insight affects adherence and treatment outcome and relates to cognitive impairment and psychopathology. We investigated the relationship of insight with cognition in patients with major depression, schizophrenia and bipolar disorder in acute psychiatric care, long-term inpatient, and outpatient settings. Methods: Eighty-one patients (women, 59.5%; age, 45.9 +/- 13.5 years; 27 in each setting group; 33.3% with DSM-IV bipolar disorder, 39.5% with unipolar major depression, and 27.2% with schizophrenia) underwent the Wisconsin Card Sorting Test (WCST) to test flexibility, clinician-rated Scale to Assess Unawareness of Mental Disorder (SUMD), and self-rated Insight Scale (IS) to assess insight/awareness. Results: Poor performance on the WCST correlated with higher SUMD scores such as current psychiatric illness unawareness, impaired symptom attribution, unawareness of medication effect, or of social consequences, but not with IS scores. The latter correlated with days on continuous treatment. Patients receiving psycho-education showed greater symptom awareness compared to patients treated with drugs alone. Cognitive flexibility and diagnostic category did not correlate. Poor insight corresponded with severe mental illness, particularly acute psychosis. Conclusions: Treatment setting specificity reflects psychopathology and severity. Insight is inversely proportional to illness severity and cognitive flexibility, which is also affected by psychopathology. Limitations comprise group heterogeneity, cross-sectional design, and limited sample size. Copyright (C) 2012 S. Karger AG, Basel C1 [Talamo, Alessandra] Univ Roma La Sapienza, Dept Neurosci Mental Hlth & Sensory Funct NESMOS, Sch Med 2, St Andrea Hosp,Unit Psychiat, IT-00189 Rome, Italy. [Bandinelli, Pier Luca; Ducci, Giuseppe] Roma E Hlth Trust, Acute Psychiat Care Unit, Dept Mental Hlth, San Filippo Neri Hosp, Rome, Italy. [Talamo, Alessandra] Harvard Univ, Sch Med, Dept Psychiat,McLean Div,Massachusetts Gen Hosp, Int Consortium Bipolar & Psychot Disorders Res, Boston, MA 02115 USA. RP Talamo, A (reprint author), Univ Roma La Sapienza, Dept Neurosci Mental Hlth & Sensory Funct NESMOS, Sch Med 2, St Andrea Hosp,Unit Psychiat, Via Grottarossa 1035-1039, IT-00189 Rome, Italy. EM atalamo@mclean.org RI Manfredi, Giovanni/C-2176-2011; OI Tatarelli, Roberto/0000-0003-4396-2632; Talamo, Alessandra/0000-0001-7321-9247 NR 61 TC 13 Z9 13 U1 3 U2 14 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0254-4962 J9 PSYCHOPATHOLOGY JI Psychopathology PY 2012 VL 45 IS 4 BP 235 EP 243 DI 10.1159/000329998 PG 9 WC Psychiatry SC Psychiatry GA 960IA UT WOS:000305380000005 PM 22627702 ER PT B AU Hutter, MM AF Hutter, Matthew M. BE Tichansky, DS Morton, J Jones, DB TI Data Drives Quality: ACS-NSQIP SO SAGES MANNUAL OF QUALITY, OUTCOMES AND PATIENT SAFETY LA English DT Article; Book Chapter ID SURGICAL QUALITY; IMPROVEMENT PROGRAM; OUTCOMES; SURGERY; SAFETY; CARE RP Hutter, MM (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, 55 Fruit St, Boston, MA 02114 USA. NR 10 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 978-1-4419-7900-1 PY 2012 BP 111 EP 118 DI 10.1007/978-1-4419-7901-8_12 D2 10.1007/978-1-4419-7901-8 PG 8 WC Medicine, General & Internal; Surgery SC General & Internal Medicine; Surgery GA BAF37 UT WOS:000304017200013 ER PT B AU Gee, DW Rattner, DW AF Gee, Denise W. Rattner, David W. BE Tichansky, DS Morton, J Jones, DB TI NOTES: Common Complications and Management SO SAGES MANNUAL OF QUALITY, OUTCOMES AND PATIENT SAFETY LA English DT Article; Book Chapter ID ORIFICE TRANSESOPHAGEAL MEDIASTINOSCOPY; TRANSGASTRIC ENDOSCOPIC PERITONEOSCOPY; SAFETY VALVE TECHNIQUE; HELLER MYOTOMY; SURGERY-NOTES; SUBMUCOSAL ENDOSCOPY; NOTES ACCESS; SURVIVAL; CAVITY; CHOLECYSTECTOMY C1 [Gee, Denise W.] Massachusetts Gen Hosp, Div Gen & Gastrointestinal Surg, Boston, MA 02459 USA. [Rattner, David W.] Massachusetts Gen Hosp, Div Gastrointestinal & Gen Surg, Boston, MA 02114 USA. RP Gee, DW (reprint author), Massachusetts Gen Hosp, Div Gen & Gastrointestinal Surg, 15 Parkman St,WACC460, Boston, MA 02459 USA. NR 26 TC 0 Z9 1 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 978-1-4419-7900-1 PY 2012 BP 355 EP 366 DI 10.1007/978-1-4419-7901-8_35 D2 10.1007/978-1-4419-7901-8 PG 12 WC Medicine, General & Internal; Surgery SC General & Internal Medicine; Surgery GA BAF37 UT WOS:000304017200036 ER PT B AU Hutter, MM AF Hutter, Matthew M. BE Tichansky, DS Morton, J Jones, DB TI The Culture of Safety and the Era of Better Practices SO SAGES MANNUAL OF QUALITY, OUTCOMES AND PATIENT SAFETY LA English DT Editorial Material; Book Chapter RP Hutter, MM (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, 55 Fruit St, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 978-1-4419-7900-1 PY 2012 BP 577 EP 578 DI 10.1007/978-1-4419-7901-8_59 D2 10.1007/978-1-4419-7901-8 PG 2 WC Medicine, General & Internal; Surgery SC General & Internal Medicine; Surgery GA BAF37 UT WOS:000304017200060 ER PT B AU Gupta, R Jones, DB Callery, MP AF Gupta, Rahul Jones, Daniel B. Callery, Mark P. BE Soper, NJ ScottConner, CEH TI Cholangiography SO SAGES MANUAL, VOL 1: BASIC LAPAROSCOPY AND ENDOSCOPY, THIRD EDITION LA English DT Article; Book Chapter ID BILE-DUCT INJURIES; LAPAROSCOPIC CHOLECYSTECTOMY; INTRAOPERATIVE ULTRASONOGRAPHY; OPERATIVE CHOLANGIOGRAPHY; ROUTINE C1 [Gupta, Rahul; Jones, Daniel B.; Callery, Mark P.] Beth Israel Deaconess Med Ctr, Dept Surg, Div Gen Surg, Boston, MA 02215 USA. RP Gupta, R (reprint author), Beth Israel Deaconess Med Ctr, Dept Surg, Div Gen Surg, 330 Brookline Ave, Boston, MA 02215 USA. NR 20 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 978-1-4614-2343-0 PY 2012 BP 273 EP 289 DI 10.1007/978-1-4614-2344-7_22 D2 10.1007/978-1-4614-2344-7 PG 17 WC Gastroenterology & Hepatology; Surgery SC Gastroenterology & Hepatology; Surgery GA BAB44 UT WOS:000303689400022 ER PT B AU Sasaki, H Stashenko, P AF Sasaki, Hajime Stashenko, Philip BE Hargreaves, KM Goodis, HE Tay, FR TI Interrelationship of the Pulp and Apical Periodontitis SO SELTZER AND BENDER'S DENTAL PULP, SECOND EDITION LA English DT Article; Book Chapter ID TUMOR-NECROSIS-FACTOR; REGULATORY T-CELLS; HUMAN PERIAPICAL LESIONS; LEUKOCYTE ADHESION DEFICIENCY; BONE-RESORBING ACTIVITY; HUMAN DENTAL-PULP; MONOCYTE CHEMOATTRACTANT PROTEIN-1; ARACHIDONIC-ACID METABOLISM; HUMAN PERIRADICULAR LESIONS; MIXED ANAEROBIC INFECTION C1 [Stashenko, Philip] Harvard Univ, Dept Oral Med Infect & Immun, Cambridge, MA 02138 USA. [Stashenko, Philip] Forsyth Inst, Cambridge, MA USA. NR 243 TC 3 Z9 3 U1 0 U2 0 PU QUINTESSENCE PUBLISHING CO INC PI HANOVER PARK PA 4350 CHANDLER DRIVE, HANOVER PARK, IL 60133 USA BN 978-0-86715-480-1 PY 2012 BP 277 EP 299 PG 23 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA BZI22 UT WOS:000301676000012 ER PT S AU Joseph, CS Yaroslavsky, AN Neel, VA Goyette, TM Giles, RH AF Joseph, Cecil S. Yaroslavsky, Anna N. Neel, Victor A. Goyette, Thomas M. Giles, Robert H. BE Sadwick, LP OSullivan, CM TI Continuous-Wave Terahertz Reflection Imaging of Ex-Vivo Nonmelanoma Skin Cancers SO TERAHERTZ TECHNOLOGY AND APPLICATIONS V SE Proceedings of SPIE LA English DT Proceedings Paper CT Conference on Terahertz Technology and Applications V CY JAN 25-26, 2012 CL San Francisco, CA SP SPIE DE Terahertz spectroscopy; continuous wave terahertz imaging; skin cancer imaging ID BASAL-CELL CARCINOMA; RADIATION; TISSUE; TUMORS; WATER AB Nonmelanoma skin cancers are the most common form of cancer. Continuous wave terahertz imaging has the potential to differentiate between nonmelanoma skin cancers and normal skin. Terahertz imaging is non-ionizing and offers a high sensitivity to water content. Contrast between cancerous and normal tissue in transmission mode has already been demonstrated using a continuous wave terahertz system. The aim of this experiment was to implement a system that is capable of reflection modality imaging of nonmelanoma skin cancers. Fresh excisions of skin cancer specimens were obtained from Mohs surgeries for this study. A CO2 optically pumped far-infrared molecular gas laser was used for illuminating the tissue at 584 GHz. The reflected signal was detected using a liquid Helium cooled Silicon bolometer. The terahertz images were compared with sample histology. The terahertz reflection images exhibit some artifacts that can hamper the specificity. The beam waist at the sample plane was measured to be 0.57 mm, and the system's signal-to-noise ratio was measured to be 65 dB. C1 [Joseph, Cecil S.; Goyette, Thomas M.; Giles, Robert H.] Univ Massachusetts, Submillimeter Wave Technol Lab, 175 Cabot St, Lowell, MA 01854 USA. [Yaroslavsky, Anna N.] Univ Massachusetts, Adv Biophoton Lab, 175 Cabot St, Lowell, MA 01854 USA. [Yaroslavsky, Anna N.; Neel, Victor A.] Massachusetts Gen Hosp, Harvard Med Sch, Dept Dermatol, Boston, MA 02114 USA. RP Joseph, CS (reprint author), Univ Massachusetts, Submillimeter Wave Technol Lab, 175 Cabot St, Lowell, MA 01854 USA. NR 24 TC 1 Z9 1 U1 1 U2 16 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-0-8194-8904-3 J9 PROC SPIE PY 2012 VL 8261 AR 82610X DI 10.1117/12.909135 PG 7 WC Optics; Radiology, Nuclear Medicine & Medical Imaging; Spectroscopy SC Optics; Radiology, Nuclear Medicine & Medical Imaging; Spectroscopy GA BAP69 UT WOS:000305073700027 ER PT B AU Lane, SW Williams, DA AF Lane, Steven W. Williams, David A. BE Scatena, R Mordente, A Giardina, B TI Leukemia Stem Cells SO ADVANCES IN CANCER STEM CELL BIOLOGY LA English DT Article; Book Chapter ID ACUTE MYELOID-LEUKEMIA; ACUTE MYELOGENOUS LEUKEMIA; HEMATOPOIETIC PROGENITOR CELLS; ACUTE PROMYELOCYTIC LEUKEMIA; GUANOSINE TRIPHOSPHATASES REPRESENT; ACUTE LYMPHOBLASTIC-LEUKEMIA; RECEPTOR-ALPHA CHAIN; BONE-MARROW; INITIATING CELLS; BCR-ABL C1 [Lane, Steven W.] Queensland Inst Med Res, Div Immunol, Brisbane, Qld 4006, Australia. [Williams, David A.] Harvard Univ, Sch Med, Dept Pediat, Div Hematol Oncol,Childrens Hosp Boston, Boston, MA 02115 USA. [Williams, David A.] Harvard Stem Cell Inst, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA USA. [Lane, Steven W.] Queenland Inst Med Res, Div Immonol, Brisbane, Qld, Australia. RP Lane, SW (reprint author), Queensland Inst Med Res, Div Immunol, Brisbane, Qld 4006, Australia. EM steven.lane@gimr.edu.au NR 109 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 978-1-4614-0808-6 PY 2012 BP 85 EP 103 DI 10.1007/978-1-4614-0809-3_6 D2 10.1007/978-1-4614-0809-3 PG 19 WC Oncology; Cell Biology; Medicine, Research & Experimental SC Oncology; Cell Biology; Research & Experimental Medicine GA BZK10 UT WOS:000301803600006 ER PT J AU Gaffo, AL Jacobs, DR Lewis, CE Mikuls, TR Saag, KG AF Gaffo, Angelo L. Jacobs, David R., Jr. Lewis, Cora E. Mikuls, Ted R. Saag, Kenneth G. TI Association between being African-American, serum urate levels and the risk of developing hyperuricemia: findings from the Coronary Artery Risk Development in Young Adults cohort SO ARTHRITIS RESEARCH & THERAPY LA English DT Article ID NUTRITION EXAMINATION SURVEY; 3RD NATIONAL-HEALTH; URIC-ACID LEVELS; RACIAL-DIFFERENCES; KIDNEY-DISEASE; RENAL-DISEASE; UNITED-STATES; CARDIA; PREVALENCE; BLACK AB Introduction: Findings that African-American race/ethnicity is associated with higher concentrations of serum urate have not been adjusted for possible confounding factors or have not explored this question as a primary outcome. We tested this hypothesis in a bi-racial cohort of younger African-American and white men and women. Methods: Data from 5,049 participants at the Coronary Artery Risk Development in Young Adults (CARDIA) cohort baseline (1985 to1986) and follow-up for up to 20 years of individuals without hyperuricemia (defined as a serum urate of 6.8 mg/dL or more) at baseline were utilized. We determined associations between race, serum urate and the development of hyperuricemia in sex-specific cross-sectional and longitudinal analyses. Confounding factors examined included: age at enrollment, body mass index, development of hypertension, glomerular filtration rate, medication use, diet and alcohol intake and menopausal symptoms in women. Results: Referent to whites, African-American men and women had significantly lower concentrations of serum urate at baseline. African-American men had an essentially equal risk of developing incident hyperuricemia during follow-up compared with white men (multivariable adjusted HR = 1.12 (0.88 to1.40)). African-American women developed a significantly increased risk of hyperuricemia when compared to white women (HR = 2.31 (1.34 to 3.99)). Conclusions: Young African-American men and women had lower concentrations of serum urate than whites. During longitudinal follow-up, African-American women had a significantly increased risk of developing hyperuricemia when compared with white women, a difference that was not observed in men. Differences in production of serum urate or a more rapid decline in fractional excretion of serum urate are potential, albeit still unproven, explanations for these findings in African-American women. C1 [Gaffo, Angelo L.; Saag, Kenneth G.] Div Rheumatol, Birmingham, AL 35294 USA. [Gaffo, Angelo L.] Birmingham VA Med Ctr, Birmingham, AL 35233 USA. [Jacobs, David R., Jr.] Univ Minnesota, Sch Publ Hlth, Div Epidemiol & Community Hlth, Minneapolis, MN 55454 USA. [Jacobs, David R., Jr.] Univ Oslo, Dept Nutr, N-0316 Oslo, Norway. [Lewis, Cora E.] Univ Alabama Birmingham, Dept Med, Div Prevent Med, Birmingham, AL 35294 USA. [Mikuls, Ted R.] Univ Nebraska Med Ctr, Sect Rheumatol & Immunol, Omaha, NE 68198 USA. RP Saag, KG (reprint author), Div Rheumatol, 172 Shelby Interdisciplinary Biomed Res Bldg,1825, Birmingham, AL 35294 USA. EM ksaag@uab.edu FU University of Alabama at Birmingham, Coordinating Center [N01-HC-95095]; University of Alabama at Birmingham, Field Center [N01-HC-48047]; University of Minnesota, Field Center and Diet Reading Center [N01-HC 48048]; Northwestern University, Field Center [N01-HC-48049]; Kaiser Foundation Research Institute [N01-HC-48050]; University of California, Irvine, Echocardiography Reading Center [N01-HC-45134]; Harbor-UCLA Research Education Institute, Computed Tomography Reading Center [N01-HC-05187]; Wake Forest University [N01-HC-45205]; New England Medical Center from the National Heart, Lung and Blood Institute [N01-HC-45204] FX Work on this manuscript was supported (or partially supported) by contracts: University of Alabama at Birmingham, Coordinating Center, N01-HC-95095; University of Alabama at Birmingham, Field Center, N01-HC-48047; University of Minnesota, Field Center and Diet Reading Center (Year 20 Exam), N01-HC 48048; Northwestern University, Field Center, N01-HC-48049; Kaiser Foundation Research Institute, N01-HC-48050; University of California, Irvine, Echocardiography Reading Center (Year 5 and 10), N01-HC-45134; Harbor-UCLA Research Education Institute, Computed Tomography Reading Center (Year 15 Exam), N01-HC-05187; Wake Forest University (Year 20 Exam), N01-HC-45205; New England Medical Center (Year 20 Exam), N01-HC-45204 from the National Heart, Lung and Blood Institute. NHLBI had input into the overall design and conduct of the CARDIA study. NR 32 TC 11 Z9 11 U1 0 U2 2 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1478-6354 J9 ARTHRITIS RES THER JI Arthritis Res. Ther. PY 2012 VL 14 IS 1 AR R4 DI 10.1186/ar3552 PG 7 WC Rheumatology SC Rheumatology GA 951CQ UT WOS:000304698800018 PM 22225548 ER PT J AU Nabatian, AS Bashir, MM Wysocka, M Sharma, M Werth, VP AF Nabatian, Adam S. Bashir, Muhammad M. Wysocka, Maria Sharma, Meena Werth, Victoria P. TI Tumor necrosis factor alpha release in peripheral blood mononuclear cells of cutaneous lupus and dermatomyositis patients SO ARTHRITIS RESEARCH & THERAPY LA English DT Article ID HUMAN DENDRITIC CELLS; TNF-ALPHA; ENDOTHELIAL-CELLS; SKIN DISEASES; ERYTHEMATOSUS; RECEPTORS; PSORIASIS; CYTOKINES; LESIONS; ACCUMULATION AB Introduction: Several studies have reported that TNF alpha is substantially increased within skin lesions of patients with discoid lupus erythematosus (DLE), subacute cutaneous lupus erythematosus (SCLE) and dermatomyositis (DM) compared to controls. Elevated TNF alpha has been reported in the sera of some patients with systemic lupus erythematosus, DLE and SCLE, but not in the sera of patients with DM. Because of the key pathogenic role of autoimmunity in these diseases, in this study we sought to evaluate TNF alpha production by a readily available source of immune cells (namely, peripheral blood mononuclear cells (PBMCs)) taken from controls and from patients with cutaneous lupus or DM. Methods: Freshly isolated PBMCs were cultured overnight, and TNF alpha protein accumulation in conditioned medium was determined. In addition, flow cytometry using cell-type-specific markers was performed to determine the sources of TNF alpha. One-way analysis of variance and Dunnett's multiple comparisons test were performed for statistical comparisons. Results: Accumulation of TNF alpha protein in conditioned medium containing PBMCs from DLE patients, but not from SCLE, TLE or DM patients, was significantly greater (19-fold) than that from controls (P < 0.001). In DLE PBMCs, increased TNF alpha was produced by circulating monocytes and myeloid dendritic cells (mDCs). The mean TNF alpha fluorescence intensity, but not the total number, of both monocytes and mDCs (P < 0.01) from DLE patients was significantly greater (2.3-fold) than that of controls. There were significantly more (13.3-fold) mDCs with intracellular TNF alpha in blood from DLE patients (P < 0.001) and DM patients (P < 0.001) compared to controls. Most importantly, a positive correlation was seen in DLE patients between their disease activity measured using the Cutaneous Lupus Erythematosus Disease Area and Severity Index and TNF alpha protein secretion (r = 0.61, P < 0.08). Conclusions: TNF alpha protein production by PBMCs is greater in DLE patients than in patients with other cutaneous forms of lupus and DM or in controls. Flow cytometric studies demonstrated that circulating monocytes and mDCs contributed to this increased TNF alpha production. Monocytes and mDCs are present in lesional skin, and the increased TNF alpha production by these cells and other PBMCs likely increase the number of inflammatory cells seen in DLE skin relative to other subsets of cutaneous lupus erythematosus and DM. These results provide a possible biological explanation for the denser infiltrate seen in DLE relative to DM. C1 [Nabatian, Adam S.; Bashir, Muhammad M.; Sharma, Meena; Werth, Victoria P.] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. [Nabatian, Adam S.; Bashir, Muhammad M.; Wysocka, Maria; Sharma, Meena; Werth, Victoria P.] Univ Penn, Dept Dermatol, Sch Med, Philadelphia, PA 19104 USA. [Nabatian, Adam S.] Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Piscataway, NJ 08854 USA. RP Werth, VP (reprint author), Philadelphia Vet Affairs Med Ctr, 38th & Woodland Ave, Philadelphia, PA USA. EM werth@mail.med.upenn.edu FU Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Biomedical Laboratory Research and Development; National Institutes of Health (NIH) [K24-AR 02207] FX This study was supported in part by a merit review grant from the Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Biomedical Laboratory Research and Development, and by National Institutes of Health (NIH) grant K24-AR 02207 (to VPW).). In addition, funding was provided by the Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Biomedical Laboratory Research and Development. NR 36 TC 9 Z9 9 U1 0 U2 3 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1478-6354 J9 ARTHRITIS RES THER JI Arthritis Res. Ther. PY 2012 VL 14 IS 1 AR R1 DI 10.1186/ar3549 PG 11 WC Rheumatology SC Rheumatology GA 951CQ UT WOS:000304698800015 PM 22217359 ER PT J AU Rao, SM Auger, JL Gaillard, P Weissleder, R Wada, E Torres, R Kojima, M Benoist, C Mathis, D Binstadt, BA AF Rao, Sindhuja M. Auger, Jennifer L. Gaillard, Philippe Weissleder, Ralph Wada, Etsuko Torres, Richard Kojima, Masayasu Benoist, Christophe Mathis, Diane Binstadt, Bryce A. TI The neuropeptide neuromedin U promotes autoantibody-mediated arthritis SO ARTHRITIS RESEARCH & THERAPY LA English DT Article ID INFLAMMATORY ARTHRITIS; THERAPEUTIC TARGET; SIGNALING PATHWAY; MOUSE MODEL; MAST-CELLS; RECEPTORS; IMMUNE; MICE; NEUTROPHILS; INITIATION AB Introduction: Neuromedin U (NMU) is a neuropeptide with pro-inflammatory activity. The primary goal of this study was to determine if NMU promotes autoantibody-induced arthritis. Additional studies addressed the cellular source of NMU and sought to define the NMU receptor responsible for its pro-inflammatory effects. Methods: Serum containing arthritogenic autoantibodies from K/BxN mice was used to induce arthritis in mice genetically lacking NMU. Parallel experiments examined whether NMU deficiency impacted the early mast-cell-dependent vascular leak response induced by these autoantibodies. Bone-marrow chimeric mice were generated to determine whether pro-inflammatory NMU is derived from hematopoietic cells or stromal cells. Mice lacking the known NMU receptors singly and in combination were used to determine susceptibility to serum-transferred arthritis and in vitro cellular responses to NMU. Results: NMU-deficient mice developed less severe arthritis than control mice. Vascular leak was not affected by NMU deficiency. NMU expression by bone-marrow-derived cells mediated the pro-arthritogenic effect. Deficiency of all of the known NMU receptors, however, had no impact on arthritis severity and did not affect the ability of NMU to stimulate intracellular calcium flux. Conclusions: NMU-deficient mice are protected from developing autoantibody-induced inflammatory arthritis. NMU derived from hematopoietic cells, not neurons, promotes the development of autoantibody-induced inflammatory arthritis. This effect is mediated by a receptor other than the currently known NMU receptors. C1 [Rao, Sindhuja M.; Auger, Jennifer L.; Binstadt, Bryce A.] Univ Minnesota, Ctr Immunol, Minneapolis, MN 55414 USA. [Rao, Sindhuja M.; Auger, Jennifer L.; Binstadt, Bryce A.] Univ Minnesota, Dept Pediat, Minneapolis, MN 55414 USA. [Rao, Sindhuja M.] Washington Univ, Dept Med, Div Rheumatol, St Louis, MO 63110 USA. [Gaillard, Philippe] Univ Minnesota, Biostat Design & Anal Ctr, Clin & Translat Sci Inst, Minneapolis, MN 55414 USA. [Weissleder, Ralph] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. [Weissleder, Ralph] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Wada, Etsuko] NCNP, Natl Inst Neurosci, Dept Degenerat Neurol Dis, Tokyo 187, Japan. [Torres, Richard] Regeneron Pharmaceut Inc, Tarrytown, NY 10591 USA. [Kojima, Masayasu] Kurume Univ, Inst Life Sci, Dept Mol Genet, Kurume, Fukuoka 8390842, Japan. [Benoist, Christophe; Mathis, Diane] Harvard Univ, Dept Pathol, Sch Med, Boston, MA 02215 USA. RP Binstadt, BA (reprint author), Univ Minnesota, Ctr Immunol, Med Biosci Bldg,2101 6th St SE, Minneapolis, MN 55414 USA. EM binstadt@umn.edu RI Binstadt, Bryce/N-1305-2013 OI Binstadt, Bryce/0000-0003-3127-3856 FU Arthritis Foundation; Minnesota Medical Foundation; National Institute of Arthritis and Musculoskeletal and Skin Diseases [K08 AR054317]; University of Minnesota Department of Pediatrics; [R01 AR055271] FX We thank Pratik Patel and Donna Skinner for technical assistance. The studies were supported by an Arthritis Foundation Arthritis Investigator Award and a Minnesota Medical Foundation Research Grant (to BAB). BAB is also supported by K08 AR054317 from the National Institute of Arthritis and Musculoskeletal and Skin Diseases and by start-up funds from the University of Minnesota Department of Pediatrics. CB and DM's participation was supported by R01 AR055271. NR 33 TC 2 Z9 3 U1 1 U2 3 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1478-6354 J9 ARTHRITIS RES THER JI Arthritis Res. Ther. PY 2012 VL 14 IS 1 AR R29 DI 10.1186/ar3732 PG 8 WC Rheumatology SC Rheumatology GA 951CQ UT WOS:000304698800043 PM 22314006 ER PT S AU Tanaka, M Mroz, P Dai, T Kinoshita, M Morimoto, Y Hamblin, MR AF Tanaka, Masamitsu Mroz, Pawel Dai, Tianhong Kinoshita, Manabu Morimoto, Yuji Hamblin, Michael R. BE Chen, WR TI Photodynamic therapy can induce non-specific protective immunity against a bacterial infection SO BIOPHOTONICS AND IMMUNE RESPONSES VII SE Proceedings of SPIE LA English DT Proceedings Paper CT Conference on Biophotonics and Immune Responses VII CY JAN 23, 2012 CL San Francisco, CA SP SPIE DE bacterial arthritis; photodynamic therapy; intra-articular photosensitizer; biphasic dose response; neutrophil attraction ID RESISTANT STAPHYLOCOCCUS-AUREUS; BIOFILM INFECTIONS AB Photodynamic therapy (PDT) for cancer is known to induce an immune response against the tumor, in addition to its well-known direct cell-killing and vascular destructive effects. PDT is becoming increasingly used as a therapy for localized infections. However there has not to date been a convincing report of an immune response being generated against a microbial pathogen after PDT in an animal model. We have studied PDT as a therapy for bacterial arthritis caused by Staphylococcus aureus infection in the mouse knee. We had previously found that PDT of an infection caused by injection of MRSA (5X10(7) CFU) into the mouse knee followed 3 days later by 1 mu g of Photofrin and 635-nm diode laser illumination with a range of fluences within 5 minutes, gave a biphasic dose response. The greatest reduction of MRSA CFU was seen with a fluence of 20 J/cm(2), whereas lower antibacterial efficacy was observed with fluences that were either lower or higher. We then tested the hypothesis that the host immune response mediated by neutrophils was responsible for most of the beneficial antibacterial effect. We used bioluminescence imaging of luciferase expressing bacteria to follow the progress of the infection in real time. We found similar results using intra-articular methylene blue and red light, and more importantly, that carrying out PDT of the noninfected joint and subsequently injecting bacteria after PDT led to a significant protection from infection. Taken together with substantial data from studies using blocking antibodies we believe that the pre-conditioning PDT regimen recruits and stimulates neutrophils into the infected joint which can then destroy bacteria that are subsequently injected and prevent infection. C1 [Tanaka, Masamitsu; Mroz, Pawel; Dai, Tianhong; Hamblin, Michael R.] Massachusetts Gen Hosp, Wellman Ctr Photomed, BAR414,40 Blossom St, Boston, MA 02114 USA. [Tanaka, Masamitsu; Mroz, Pawel; Dai, Tianhong; Hamblin, Michael R.] Harvard Med Sch, Dept Dermatol, Boston, MA 02115 USA. [Tanaka, Masamitsu] Natl Def Med Coll, Dept Orthopaed Surg, Tokorozawa, Saitama, Japan. [Mroz, Pawel] Northwestern Mem Hosp, Dept Pathol, Chicago, IL 60611 USA. [Hamblin, Michael R.] Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. [Kinoshita, Manabu] Natl Def Med Coll, Dept Immunol & Microbiol, Tokorozawa, Saitama, Japan. [Morimoto, Yuji] Natl Def Med Coll, Dept Integrat Physiol & Bio Nano Med, Tokorozawa, Saitama, Japan. 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 US NIH [R01AI050875]; MRH; Tianhong Dai by an Airlift Research Foundation Extremity Trauma Research [109421]; Ministry of Education, Culture, Sports, Science and Technology of Japan [23659628] FX Liyi Huang and Michael R. Hamblin were supported by US NIH grant R01AI050875 to MRH and Tianhong Dai by an Airlift Research Foundation Extremity Trauma Research Grant (grant 109421). This work was supported by a Grant-in-Aid for Challenging Exploratory Research (23659628) from the Ministry of Education, Culture, Sports, Science and Technology of Japan to Yuji Morimoto. NR 15 TC 0 Z9 0 U1 0 U2 3 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-0-8194-8867-1 J9 PROC SPIE PY 2012 VL 8224 DI 10.1117/12.906012 PG 9 WC Optics; Radiology, Nuclear Medicine & Medical Imaging SC Optics; Radiology, Nuclear Medicine & Medical Imaging GA BAP74 UT WOS:000305117000001 ER PT J AU Elia, AEH Elledge, SJ AF Elia, Andrew E. H. Elledge, Stephen J. TI BRCA1 as tumor suppressor: lord without its RING? SO BREAST CANCER RESEARCH LA English DT Article ID UBIQUITIN; BINDING; RECOGNITION; COMPLEX; REPAIR; DOMAIN AB BRCA1 is a tumor suppressor with critical roles in the maintenance of genomic stability. It encodes a large protein with an amino-terminal RING domain that possesses ubiquitin-ligase activity. Given the occurrence of numerous cancer-causing mutations within its RING domain, investigators have long suspected that BRCA1's ubiquitin ligase is important for its tumor suppression and DNA repair activities. Using genetically engineered mouse models, two recent studies shed light on this age-old hypothesis. C1 [Elia, Andrew E. H.; Elledge, Stephen J.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. [Elia, Andrew E. H.; Elledge, Stephen J.] Brigham & Womens Hosp, Div Genet, Boston, MA 02115 USA. [Elia, Andrew E. H.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. RP Elledge, SJ (reprint author), Harvard Univ, Sch Med, Dept Genet, 77 Ave Louis Pasteur,NRB158, Boston, MA 02115 USA. EM selledge@genetics.med.harvard.edu FU Jane Coffin Childs Foundation; American Society for Radiation Oncology FX AEHE is supported by fellowships from The Jane Coffin Childs Foundation and The American Society for Radiation Oncology. SJE is an investigator with the Howard Hughes Medical Institute. NR 15 TC 3 Z9 3 U1 0 U2 1 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1465-542X J9 BREAST CANCER RES JI Breast Cancer Res. PY 2012 VL 14 IS 2 AR 306 DI 10.1186/bcr3118 PG 3 WC Oncology SC Oncology GA 952DZ UT WOS:000304771800008 PM 22494569 ER PT J AU Liu, MH Wang, LW Bongartz, T Hawse, JR Markovic, SN Schaid, DJ Mushiroda, T Kubo, M Nakamura, Y Kamatani, N Goss, PE Ingle, JN Weinshilboum, RM AF Liu, Mohan Wang, Liewei Bongartz, Tim Hawse, John R. Markovic, Svetomir N. Schaid, Daniel J. Mushiroda, Taisei Kubo, Michiaki Nakamura, Yusuke Kamatani, Naoyuki Goss, Paul E. Ingle, James N. Weinshilboum, Richard M. TI Aromatase inhibitors, estrogens and musculoskeletal pain: estrogen-dependent T-cell leukemia 1A (TCL1A) gene-mediated regulation of cytokine expression SO BREAST CANCER RESEARCH LA English DT Article ID NF-KAPPA-B; AKT KINASE COACTIVATOR; EARLY BREAST-CANCER; RECEPTOR; ACTIVATION; ARTHRITIS; THERAPY; PATHWAY; ALPHA; WOMEN AB Introduction: Arthralgias and myalgias are major side effects associated with aromatase inhibitor (AI) therapy of breast cancer. In a recent genome-wide association study, we identified SNPs - including one that created an estrogen response element near the 3' end of the T-cell leukemia 1A (TCL1A) gene - that were associated with musculoskeletal pain in women on adjuvant AI therapy for breast cancer. We also showed estrogen-dependent, SNP-modulated variation in TCL1A expression and, in preliminary experiments, showed that TCL1A could induce IL-17RA expression. In the present study, we set out to determine whether these SNPs might influence cytokine expression and effect more widely, and, if so, to explore the mechanism of TCL1A-related AI-induced side effects. Methods: The functional genomic experiments performed included determinations of TCL1A, cytokine and cytokine receptor expression in response to estrogen treatment of U2OS cells and lymphoblastoid cell lines that had been stably transfected with estrogen receptor alpha. Changes in mRNA and protein expression after gene knockdown and overexpression were also determined, as was NF-kappa B transcriptional activity. Results: Estradiol (E2) increased TCL1A expression and, in a TCL1A SNP-dependent fashion, also altered the expression of IL-17, IL-17RA, IL-12, IL-12RB2 and IL-1R2. TCL1A expression was higher in E2-treated lymphoblastoid cell lines with variant SNP genotypes, and induction of the expression of cytokine and cytokine receptor genes was mediated by TCL1A. Finally, estrogen receptor alpha blockade with ICI-182,780 in the presence of E2 resulted in greatly increased NF-kappa B transcriptional activity, but only in cells that carried variant SNP genotypes. These results linked variant TCL1A SNP sequences that are associated with AI-dependent musculoskeletal pain with increased E2-dependent TCL1A expression and with downstream alterations in cytokine and cytokine receptor expression as well as NF-kappa B transcriptional activity. Conclusions: SNPs near the 3' terminus of TCL1A were associated with AI-dependent musculoskeletal pain. E2 induced SNP-dependent TCL1A expression, which in turn altered IL-17, IL-17RA, IL-12, IL-12RB2, and IL-1R2 expression as well as NF-kappa B transcriptional activity. These results provide a pharmacogenomic explanation for a clinically important adverse drug reaction as well as insights into a novel estrogen-dependent mechanism for the modulation of cytokine and cytokine receptor expression. C1 [Liu, Mohan; Wang, Liewei; Weinshilboum, Richard M.] Mayo Clin, Div Clin Pharmacol, Dept Mol Pharmacol & Expt Therapeut, Rochester, MN 55905 USA. [Bongartz, Tim] Mayo Clin, Div Rheumatol, Dept Med, Rochester, MN 55905 USA. [Hawse, John R.] Mayo Clin, Dept Biochem & Mol Biol, Rochester, MN 55905 USA. [Markovic, Svetomir N.; Ingle, James N.] Mayo Clin, Div Med Oncol, Dept Oncol, Rochester, MN 55905 USA. [Schaid, Daniel J.] Mayo Clin, Dept Hlth Sci Res, Div Biomed Stat & Informat, Rochester, MN 55905 USA. [Mushiroda, Taisei; Kubo, Michiaki; Nakamura, Yusuke; Kamatani, Naoyuki] RIKEN Ctr Genom Med, Tsurumi Ku, Yokohama, Kanagawa 2300045, Japan. [Goss, Paul E.] Harvard Univ, Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. RP Weinshilboum, RM (reprint author), Mayo Clin, Div Clin Pharmacol, Dept Mol Pharmacol & Expt Therapeut, 200 1st St SW, Rochester, MN 55905 USA. EM weinshilboum.richard@mayo.edu RI Mushiroda, Taisei/E-3022-2010; Kubo, Michiaki/N-7947-2015 FU NIH (The Pharmacogenomics Research Network) [R01 GM28157, R01 CA132780, U01 HG05137, U19 GM61388]; NIH [P50 CA116201, U10 CA77202]; Mayo Clinic Center for Individualized Medicine; Ministry of Education, Culture, Sports, Science and Technology; Canadian Cancer Society [CCS 015469]; Breast Cancer Research Foundation; NIH Pharmacogenomics Research Network (PGRN) - RIKEN Center for Genomic Medicine (CGM) Global Alliance; Avon Foundation, New York, USA FX The authors thank Luanne Wussow for her assistance with the preparation of this manuscript. Funding support: NIH grants R01 GM28157, R01 CA132780, U01 HG05137, U19 GM61388 (The Pharmacogenomics Research Network), P50 CA116201, U10 CA77202, the Mayo Clinic Center for Individualized Medicine, the Biobank Japan Project funded by the Ministry of Education, Culture, Sports, Science and Technology, CCS 015469 from the Canadian Cancer Society, and the Breast Cancer Research Foundation. This study was supported, in part, by the NIH Pharmacogenomics Research Network (PGRN) - RIKEN Center for Genomic Medicine (CGM) Global Alliance. PEG is supported by the Avon Foundation, New York, USA. NR 30 TC 25 Z9 25 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1465-542X J9 BREAST CANCER RES JI Breast Cancer Res. PY 2012 VL 14 IS 2 AR R41 DI 10.1186/bcr3137 PG 11 WC Oncology SC Oncology GA 952DZ UT WOS:000304771800016 PM 22405131 ER PT J AU Schierberl, K Giordano, T Satpute, S Hao, J Kaur, G Hofmann, F Moosmang, S Striessnig, J Rajadhyaksha, A AF Schierberl, Kathryn Giordano, Thomas Satpute, Shirish Hao, Jin Kaur, Gagandeep Hofmann, Franz Moosmang, Sven Striessnig, Joerg Rajadhyaksha, Anjali TI Ca(v)1.3 L-type Ca2+ channels mediate long-term adaptation in dopamine D2L-mediated GluA1 trafficking in the dorsal striatum following cocaine exposure SO CHANNELS LA English DT Article DE cocaine; dorsal striatum; VTA; GluA1; Ca(v)1.3; dopamine D2; ERK; CREB; DARPP-32; Akt; GSK3 beta ID GLUR1 AMPA RECEPTOR; LOCOMOTOR SENSITIZATION; SEEKING BEHAVIOR; ADDICTION; PHOSPHORYLATION; MECHANISMS; EXPRESSION; PLASTICITY; DARPP-32; MEMORY AB AMPA receptor (AMPAR) plasticity at glutamatergic synapses in the mesostriatal dopaminergic pathway has been implicated in persistent cocaine-induced behavioral responses; however, the precise mechanism underlying these changes remains unknown. Utilizing cocaine psychomotor sensitization in mice we find that repeated cocaine results in a basal reduction of Ser 845 GluA1 and cell surface GluA1 levels in the dorsal striatum (dStr) following a protracted withdrawal period, an adaptation that is dependent on Ca(v)1.3 channels but not those expressed in the VTA. We find that the basally-induced decrease in this phosphoprotein is the result of recruitment of the striatal dopamine D2 pathway, as evidenced by enhanced levels of D2 receptor (D2R) mRNA expression and D2R function as examined using the D2R antagonist, eticlopride, as well as alterations in the phosphorylation status of several downstream molecular targets of D2R's, including CREB, DARPP-32, Akt and GSK3 beta. Taken together with our recently published findings examining similar phenomena in the nucleus accumbens (NAc), these results underscore the utilization of divergent molecular mechanisms in the dStr, in mediating cocaine-induced persistent behavioral changes. C1 [Schierberl, Kathryn; Rajadhyaksha, Anjali] Weill Cornell Med Coll, Grad Program Neurosci, New York, NY USA. [Giordano, Thomas; Satpute, Shirish; Rajadhyaksha, Anjali] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Martinos Ctr Biomed Engn, Charlestown, MA USA. [Giordano, Thomas; Hao, Jin; Kaur, Gagandeep; Rajadhyaksha, Anjali] Weill Cornell Med Coll, Div Pediat Neurol, Dept Pediat, New York, NY USA. [Hofmann, Franz] Tech Univ Munich, Res Grp 923, Munich, Germany. [Moosmang, Sven] Tech Univ Munich, Inst Pharmacol, Munich, Germany. [Striessnig, Joerg] Univ Innsbruck, Inst Pharm Pharmacol & Toxicol, A-6020 Innsbruck, Austria. RP Rajadhyaksha, A (reprint author), Weill Cornell Med Coll, Grad Program Neurosci, New York, NY USA. EM amr2011@med.cornell.edu OI Striessnig, Joerg/0000-0002-9406-7120 FU NIDA [K01 DA14057, R21 DA023686, DA007274-19]; Austrian Science Fund [P20670]; Deutsche Forschungsgemeinschaft FX This work was supported by NIDA Grants K01 DA14057 (A. M. R.), R21 DA023686 (A. M. R.) and DA007274-19 (K. S.), Austrian Science Fund P20670 (J.S.) and Deutsche Forschungsgemeinschaft (F.H. and S.M.). NR 37 TC 6 Z9 7 U1 0 U2 4 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 1933-6950 J9 CHANNELS JI Channels PD JAN-FEB PY 2012 VL 6 IS 1 BP 11 EP 17 DI 10.4161/chan.19324 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 953XG UT WOS:000304906500002 PM 22419037 ER PT J AU Zuniga, J Torres-Garcia, D Santos-Mendoza, T Rodriguez-Reyna, TS Granados, J Yunis, EJ AF Zuniga, Joaquin Torres-Garcia, Diana Santos-Mendoza, Teresa Rodriguez-Reyna, Tatiana S. Granados, Julio Yunis, Edmond J. TI Cellular and Humoral Mechanisms Involved in the Control of Tuberculosis SO CLINICAL & DEVELOPMENTAL IMMUNOLOGY LA English DT Review ID TUMOR-NECROSIS-FACTOR; ACTIVE PULMONARY TUBERCULOSIS; ADAPTIVE IMMUNE-RESPONSE; MEDIASTINAL LYMPH-NODES; IMPAIRED TH1 CYTOKINE; ACUTE-PHASE RESPONSE; TOLL-LIKE RECEPTORS; CLASS-II MOLECULES; LONG-TERM CONTROL; MYCOBACTERIUM-TUBERCULOSIS AB Mycobacterium tuberculosis (Mtb) infection is a major international public health problem. One-third of the world's population is thought to have latent tuberculosis, a condition where individuals are infected by the intracellular bacteria without active disease but are at risk for reactivation, if their immune system fails. Here, we discuss the role of nonspecific inflammatory responses mediated by cytokines and chemokines induced by interaction of innate receptors expressed in macrophages and dendritic cells (DCs). We also review current information regarding the importance of several cytokines including IL-17/IL-23 in the development of protective cellular and antibody-mediated protective responses against Mtb and their influence in containment of the infection. Finally, in this paper, emphasis is placed on the mechanisms of failure of Mtb control, including the immune dysregulation induced by the treatment with biological drugs in different autoimmune diseases. Further functional studies, focused on the mechanisms involved in the early host-Mtb interactions and the interplay between host innate and acquired immunity against Mtb, may be helpful to improve the understanding of protective responses in the lung and in the development of novel therapeutic and prophylactic tools in TB. C1 [Rodriguez-Reyna, Tatiana S.] Inst Nacl Ciencias Med & Nutr Salvador Zubiran, Dept Immunol & Rheumatol, Mexico City 14000, DF, Mexico. [Zuniga, Joaquin; Torres-Garcia, Diana; Santos-Mendoza, Teresa] Inst Nacl Enfermedades Resp Ismael Cosio Villegas, Lab Immunobiol & Genet, Mexico City 14080, DF, Mexico. [Granados, Julio] Inst Nacl Ciencias Med & Nutr Salvador Zubiran, Dept Transplants, Mexico City 14000, DF, Mexico. [Yunis, Edmond J.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Yunis, Edmond J.] Harvard Univ, Sch Med, Dept Canc Immunol & AIDS, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Rodriguez-Reyna, TS (reprint author), Inst Nacl Ciencias Med & Nutr Salvador Zubiran, Dept Immunol & Rheumatol, Mexico City 14000, DF, Mexico. EM sofarodriguez@yahoo.com.mx; edmond_yunis@dfci.harvard.edu FU National Council of Science and Technology of Mexico (CONACYT) [115497] FX The publication of this paper was supported by the National Council of Science and Technology of Mexico (CONACYT Grant no. 115497). NR 205 TC 33 Z9 33 U1 2 U2 16 PU HINDAWI PUBLISHING CORPORATION PI NEW YORK PA 410 PARK AVENUE, 15TH FLOOR, #287 PMB, NEW YORK, NY 10022 USA SN 1740-2522 EI 1740-2530 J9 CLIN DEV IMMUNOL JI Clin. Dev. Immunol. PY 2012 AR 193923 DI 10.1155/2012/193923 PG 18 WC Immunology SC Immunology GA 955KD UT WOS:000305016700001 ER PT J AU Shamloo, BK Chhabra, P Freedman, AN Potosky, A Malin, J Smith, SW AF Shamloo, Behrooz K. Chhabra, Pankdeep Freedman, Andrew N. Potosky, Arnold Malin, Jennifer Smith, Sheila Weiss TI Novel Adverse Events of Bevacizumab in the US FDA Adverse Event Reporting System Database A Disproportionality Analysis SO DRUG SAFETY LA English DT Article ID ENDOTHELIAL GROWTH-FACTOR; NITRIC-OXIDE SYNTHASE; METASTATIC COLORECTAL-CANCER; INTRAVITREAL BEVACIZUMAB; TUMOR-GROWTH; ANGIOGENESIS; CARCINOMA; RECEPTOR; CELLS; SURVEILLANCE AB Background: Bevacizumab is the first in its class, vascular endothelial growth factor (VEGF) inhibitor that was initially approved by the US FDA in 2004 for the treatment of metastatic colon cancer and other solid tumors. Pre-approval clinical trials, particularly for oncology drugs, are limited in their ability to detect certain adverse effects and, therefore, the FDA and pharmaceutical sponsors collect and monitor reports of adverse events (AEs) following approval. Objective: The purpose of this study was to screen the FDA's Adverse Event Reporting System (AERS) database for novel AEs that may be attributed to bevacizumab. Methods: The FDA AERS database was used to identify all AE reports for bevacizumab from February 2004 to September 2009. Disproportionality analysis was conducted for bevacizumab against all other drugs in the background by setting statistical significance at proportional reporting ratio (PRR) >= 2, observed case count >= 3 and chi-square >= 4. Subsequent clinical evaluation was performed to determine the clinical relevance of the findings and to group related events. Results: A total of 523 Preferred Terms (PTs) were disproportionally reported; following clinical review 63 (12%) were found to be both unlabelled and of clinical importance. These PTs were grouped into 15 clinical disorder groups. Among the clinical disorders, electrolyte abnormalities had the greatest number of reports (n=426) followed by cardiovascular events (n=421), gastrointestinal events (n=345), nervous system disorders (n=106) and pneumonitis (n=96). On sensitivity analysis, a number of clinically important unlabelled disorders, such as necrotizing fasciitis, vessel wall disorders, arrhythmia and conduction disorder and autoimmune thrombocytopenia still met the statistical significance criteria. Conclusions: During the study period, out of 12 010 AE reports mentioning bevacizumab, it was listed as the suspect drug in 94.2% of the reports. Our disproportionality analysis identified many events that are already recognized as AEs of bevacizumab, but it also identified a number of clinically important unlabelled terms, which if confirmed in future studies would have potential implications for use of bevacizumab in clinical practice. C1 [Chhabra, Pankdeep; Smith, Sheila Weiss] Univ Maryland, Ctr Drug Safety, Sch Pharm, Baltimore, MD 21201 USA. [Shamloo, Behrooz K.] Univ Nevada, Sch Med, Nevada Canc Inst, Las Vegas, NV 89154 USA. [Freedman, Andrew N.] NCI, NIH, Bethesda, MD 20892 USA. [Potosky, Arnold] Lombardi Comprehens Canc Ctr, Dept Oncol, Washington, DC USA. [Malin, Jennifer] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. RP Smith, SW (reprint author), Univ Maryland, Ctr Drug Safety, Sch Pharm, 220 Arch St,12th Floor, Baltimore, MD 21201 USA. EM sweiss@rx.umaryland.edu NR 37 TC 10 Z9 11 U1 0 U2 2 PU ADIS INT LTD PI AUCKLAND PA 41 CENTORIAN DR, PRIVATE BAG 65901, MAIRANGI BAY, AUCKLAND 1311, NEW ZEALAND SN 0114-5916 J9 DRUG SAFETY JI Drug Saf. PY 2012 VL 35 IS 6 BP 507 EP 518 PG 12 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy; Toxicology SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy; Toxicology GA 955TF UT WOS:000305043100008 PM 22612854 ER PT J AU Royall, DR Palmer, RF O'Bryant, SE AF Royall, Donald R. Palmer, Raymond F. O'Bryant, Sid E. CA Texas Alzheimer's Res Care TI Validation of a Latent Variable Representing the Dementing Process SO JOURNAL OF ALZHEIMERS DISEASE LA English DT Article DE Aging; cognition; dementia; functional status; g ID MILD COGNITIVE IMPAIRMENT; AMERICAN-NEUROPSYCHIATRIC-ASSOCIATION; MINI-MENTAL-STATE; GENERAL INTELLIGENCE; INSTRUMENTAL ACTIVITIES; COMMUNITY DWELLERS; COMPLEX ACTIVITIES; FUNCTIONAL STATUS; PERFORMANCE; DIAGNOSIS AB The cognitive correlates of functional status are essential to dementia case-finding. Nevertheless, cognitive performance is a generally weak predictor of functional outcomes. We have employed structural equation models to explicitly distinguish functional status, and therefore "dementia-relevant" variance in cognitive task performance (i.e., delta) from the variance that is unrelated to a dementing process (i.e., g'). Together, g' + delta encompass Spearman's g. Although delta represents only a small fraction of the total variance in cognitive task performance, it is more strongly associated with dementia status than is g'. In this study, we validate delta in a well characterized Alzheimer's disease cohort, the Texas Alzheimer's Research and Care Consortium. Our approach results in "error free" continuous variables. This suggests that delta can serve as a dementia specific endophenotype. As a result, future studies may be able to associate delta with inflammatory and genetic biomarkers. C1 [Royall, Donald R.] Univ Texas Hlth Sci Ctr San Antonio, Dept Psychiat, San Antonio, TX 78229 USA. [Royall, Donald R.] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA. [Royall, Donald R.; Palmer, Raymond F.] Univ Texas Hlth Sci Ctr San Antonio, Dept Family & Community Med, San Antonio, TX 78229 USA. [Royall, Donald R.] S Texas Vet Hlth Syst Audie L Murphy Div GRECC, San Antonio, TX USA. [O'Bryant, Sid E.] Univ N Texas Hlth Sci Ctr, Dept Internal Med, Ft Worth, TX USA. [O'Bryant, Sid E.] Univ N Texas Hlth Sci Ctr, Inst Aging & Alzheimers Dis Res, Ft Worth, TX USA. RP Royall, DR (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Psychiat, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM royall@uthscsa.edu OI O'Bryant, Sid/0000-0003-0582-5266 FU Texas Council on Alzheimer's Disease and Related Disorders FX This study was made possible by the Texas Alzheimer's Research Consortium (TARCC) funded by the state of Texas through the Texas Council on Alzheimer's Disease and Related Disorders. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 49 TC 20 Z9 20 U1 1 U2 6 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 1387-2877 J9 J ALZHEIMERS DIS JI J. Alzheimers Dis. PY 2012 VL 30 IS 3 BP 639 EP 649 DI 10.3233/JAD-2012-120055 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 955OX UT WOS:000305031400015 PM 22451315 ER PT J AU Mahoney, CR Brunye, TT Giles, GE Ditman, T Lieberman, HR Taylor, HA AF Mahoney, Caroline R. Brunye, Tad T. Giles, Grace E. Ditman, Tali Lieberman, Harris R. Taylor, Holly A. TI Caffeine increases false memory in nonhabitual consumers SO JOURNAL OF COGNITIVE PSYCHOLOGY LA English DT Article DE Arousal; Caffeine; False memory; Veridical memory ID COGNITIVE PERFORMANCE; DECLARATIVE MEMORY; STRESS; HIPPOCAMPAL; RECOGNITION; ADULTS; MOOD AB Insight into caffeine's equivocal effects on memory can be derived from work suggesting both emotional arousal and psychosocial stress increase false memory rates without increasing veridical memory. This study investigated how a range of caffeine doses affect veridical and false memory formation in nonhabitual consumers. A double-blind, repeated-measures design with caffeine (0 mg, 100 mg, 200 mg, 400 mg caffeine) was used to examine memory using the Deese-Roediger-McDermott (DRM) paradigm. Results showed that caffeine modulated arousal levels, peaking at 200 mg and returning to near baseline levels at 400 mg. Main effects of caffeine demonstrated higher critical lure recall and recognition ratings (i.e., false memory) as a function of dose, again peaking at 200 mg. Those who showed the highest arousal increases as a function of caffeine also tended to produce the highest false recall and recognition rates. Veridical memory was not affected. Results demonstrate that consumption of as little as 100 mg of caffeine elicits reliable inverted-U shape changes in arousal and, in turn, false memories in individuals who do not habitually consume caffeine. C1 [Mahoney, Caroline R.; Brunye, Tad T.; Giles, Grace E.] USA, Natick Soldier Res Dev & Engn Ctr, Natick, MA 01760 USA. [Mahoney, Caroline R.; Brunye, Tad T.; Giles, Grace E.; Ditman, Tali; Taylor, Holly A.] Tufts Univ, Dept Psychol, Medford, MA 02155 USA. [Ditman, Tali] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Lieberman, Harris R.] USA, Environm Med Res Inst, Natick, MA 01760 USA. RP Mahoney, CR (reprint author), USA, Soldier Ctr, Kansas St, Natick, MA 01760 USA. EM caroline.mahoney@us.army.mil NR 22 TC 3 Z9 3 U1 5 U2 35 PU PSYCHOLOGY PRESS PI HOVE PA 27 CHURCH RD, HOVE BN3 2FA, EAST SUSSEX, ENGLAND SN 2044-5911 J9 J COGN PSYCHOL JI J. Cogn. Psychol. PY 2012 VL 24 IS 4 BP 420 EP 427 DI 10.1080/20445911.2011.647905 PG 8 WC Psychology, Experimental SC Psychology GA 955OM UT WOS:000305030100005 ER PT S AU Antony, BJ Abramoff, MD Sonka, M Kwon, YH Garvin, MK AF Antony, Bhavna J. Abramoff, Michael D. Sonka, Milan Kwon, Young H. Garvin, Mona K. BE Haynor, DR Ourselin, S TI Incorporation of Texture-based Features in Optimal Graph-Theoretic Approach with Application to the 3-D Segmentation of Intraretinal Surfaces in SD-OCT Volumes SO MEDICAL IMAGING 2012: IMAGE PROCESSING SE Proceedings of SPIE LA English DT Proceedings Paper CT Conference on Medical Imaging - Image Processing CY FEB 06-09, 2012 CL San Diego, CA SP SPIE, Agilent Technol, Diamond SA, DQE Instruments Inc, eMagin, Isuzu Glass Co Ltd, Medtron Inc, Ocean Thin Films Inc DE Graph-theoretic approach; texture features; multiple surface segmentation; optical coherence tomography; intra-retinal surfaces ID GABOR FILTERS; SEARCH; IMAGES; MOTION AB While efficient graph-theoretic approaches exist for the optimal (with respect to a cost function) and simultaneous segmentation of multiple surfaces within volumetric medical images, the appropriate design of cost functions remains an important challenge. Previously proposed methods have used simple cost functions or optimized a combination of the same, but little has been done to design cost functions using learned features from a training set, in a less biased fashion. Here, we present a method to design cost functions for the simultaneous segmentation of multiple surfaces using the graph-theoretic approach. Classified texture features were used to create probability maps, which were incorporated into the graph-search approach. The efficiency of such an approach was tested on 10 optic nerve head centered optical coherence tomography (OCT) volumes obtained from 10 subjects that presented with glaucoma. The mean unsigned border position error was computed with respect to the average of manual tracings from two independent observers and compared to our previously reported results. A significant improvement was noted in the overall means which reduced from 9.25 +/- 4.03 mu m to 6.73 +/- 2.45 mu m (p < 0.01) and is also comparable with the inter-observer variability of 8.85 +/- 3.85 mu m. C1 [Antony, Bhavna J.; Abramoff, Michael D.; Sonka, Milan; Garvin, Mona K.] Univ Iowa, Dept Elect & Comp Engn, Iowa City, IA 52242 USA. RP Garvin, MK (reprint author), US Dept Vet Affairs, Iowa City, IA USA. EM bantony@engineering.uiowa.edu; mona-garvin@uiowa.edu NR 16 TC 2 Z9 2 U1 0 U2 1 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-0-8194-8963-0 J9 PROC SPIE PY 2012 VL 8314 AR 83141G DI 10.1117/12.911491 PG 11 WC Optics; Radiology, Nuclear Medicine & Medical Imaging SC Optics; Radiology, Nuclear Medicine & Medical Imaging GA BAN14 UT WOS:000304820000050 ER PT S AU Dagher, J Bilgin, A AF Dagher, Joseph Bilgin, Ali BE Haynor, DR Ourselin, S TI A field map estimation strategy without the noise-bandwidth tradeoff SO MEDICAL IMAGING 2012: IMAGE PROCESSING SE Proceedings of SPIE LA English DT Proceedings Paper CT Conference on Medical Imaging - Image Processing CY FEB 06-09, 2012 CL San Diego, CA SP SPIE, Agilent Technol, Diamond SA, DQE Instruments Inc, eMagin, Isuzu Glass Co Ltd, Medtron Inc, Ocean Thin Films Inc DE MRI; field inhomogeneity; distortion; field map estimation ID GEOMETRIC DISTORTION; IMAGE REGISTRATION; LOCALIZATION; FMRI AB We propose a joint acquisition-processing solution to the problem of field map estimation. Our acquisition method captures data at three echo times carefully chosen to yield optimal field map estimation using the corresponding algorithm. We show that, over an arbitrary spectral range of inhomogeneity values, our method is not subject to the traditional noise-bandwidth tradeoff. The resulting implications include: improved robustness, enhanced spectral estimation and eliminating the need for spatial phase unwrapping. Our simulations show factors of improvement in the quality of field map estimates, as compared to existing methods. Our phantom data confirms these impressive gains. C1 [Dagher, Joseph] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. [Bilgin, Ali] Univ Arizona, Inst BIO5, Dept Elect & Comp Engn, Dept Biomed Engn, Tucson, AZ 85721 USA. RP Dagher, J (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. EM dagher@nmr.mgh.harvard.edu FU NIH [T32EB013180] FX This work was supported in part by NIH funding under T32EB013180. NR 11 TC 0 Z9 0 U1 0 U2 0 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-0-8194-8963-0 J9 PROC SPIE PY 2012 VL 8314 AR 831449 DI 10.1117/12.911026 PG 7 WC Optics; Radiology, Nuclear Medicine & Medical Imaging SC Optics; Radiology, Nuclear Medicine & Medical Imaging GA BAN14 UT WOS:000304820000149 ER PT J AU Jeong, J Lee, SW Min, KS Shin, S Jun, SB Kim, SJ AF Jeong, Joonsoo Lee, Seung Woo Min, Kyou Sik Shin, Soowon Jun, Sang Beom Kim, Sung June TI Liquid Crystal Polymer (LCP), an Attractive Substrate for Retinal Implant SO SENSORS AND MATERIALS LA English DT Article DE liquid crystal polymer; retinal implant; conformable structure; planar coil; retinal prosthesis; monolithic encapsulation; soak test ID MICROELECTRODE ARRAYS; PROSTHESIS; STIMULATION; VISION; SYSTEM AB Recently, there has been growing interest in liquid crystal polymer (LCP) as a new biomaterial for next-generation implantable neural prosthetic devices. LCP has a very low moisture absorption rate compared with other polymers such as polyimide or parylene-C, providing a superior long-term reliability in the human body. In addition, LCP film is compatible with semiconductor processes, and layer-to-layer lamination is possible simply by fusion bonding of multiple LCP sheets with heat and pressure without the use of adhesives. A monolithic system can be implemented by using LCP as the substrate of electrodes and printed circuit boards as well as packaging material. Therefore, the LCP-based system can achieve a much higher long-term reliability, while maintaining the merits of conventional polymer-based systems such as thinness, flexibility, and simple fabrication procedure. In the present study, we have shown the feasibility of LCP as a substrate and packaging material for a novel monolithic retinal prosthetic device. The patterns of printed circuits and a planar coil were formed on LCP films by thin-film processes, and eye-surface-conformable structure was achieved that enables the attachment of the whole retinal implant on the eyeball. It has been verified that the spherical deformation process did not adversely affect the electrical characteristics or the performance of the printed circuits and the planar coil. The long-term reliability of LCP-encapsulation was evaluated by an in vitro accelerated soak test, and possible failure mechanisms were investigated. The LCP-encapsulation could provide reliable electrical insulation for similar to 400 days in 75 degrees C phosphate-buffered solution (PBS). C1 [Jeong, Joonsoo; Min, Kyou Sik; Shin, Soowon; Kim, Sung June] Seoul Natl Univ, Dept Elect Engn & Comp Sci, Seoul 151742, South Korea. [Jeong, Joonsoo; Min, Kyou Sik; Shin, Soowon; Kim, Sung June] Seoul Natl Univ, Interuniv Semicond Res Ctr, Seoul 151742, South Korea. [Lee, Seung Woo] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. [Jun, Sang Beom] Ewha Womans Univ, Dept Elect Engn, Seoul 120750, South Korea. RP Kim, SJ (reprint author), Seoul Natl Univ, Dept Elect Engn & Comp Sci, 1 Gwanak Ro, Seoul 151742, South Korea. EM kimsj@snu.ac.kr RI Min, Kyou Sik/M-7373-2014 FU National Research Foundation of Korea (NRF); Ministry of Education, Science and Technology [2011-0020987, SIRC-2011-0031866]; Department of Electrical Engineering, Seoul National University; National Research Foundation of Korea [2011-0007411]; Smart IT Convergence System Research Center FX This work was supported in part by the Public Welfare & Safety research program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (2011-0020987), in part by the Brain Korea 21 Project, the Department of Electrical Engineering, Seoul National University in 2011, in part by the project of the Global Ph.D. Fellowship conducted by National Research Foundation of Korea from 2011 (2011-0007411). This work was also supported by the Smart IT Convergence System Research Center funded by the Ministry of Education, Science and Technology as Global Frontier Project (SIRC-2011-0031866). NR 26 TC 11 Z9 11 U1 3 U2 22 PU MYU, SCIENTIFIC PUBLISHING DIVISION PI TOKYO PA 1-23-3-303 SENDAGI, TOKYO, 113-0022, JAPAN SN 0914-4935 J9 SENSOR MATER JI Sens. Mater. PY 2012 VL 24 IS 4 SI SI BP 189 EP 203 PG 15 WC Instruments & Instrumentation; Materials Science, Multidisciplinary SC Instruments & Instrumentation; Materials Science GA 956MI UT WOS:000305093400005 ER PT B AU Ibrahim, N Hodi, FS AF Ibrahim, Nageatte Hodi, F. Stephen BE Gajewski, TF Hodi, FS TI KIT as a Therapeutic Target for Melanoma SO TARGETED THERAPEUTICS IN MELANOMA SE Current Clinical Oncology Series LA English DT Article; Book Chapter DE KIT; CD117; Acral melanoma; Mucosal melanoma; Chronic sun-damaged skin; Imatinib; Sunitinib; Nilotinib; Dasatinib; Masatinib ID GASTROINTESTINAL STROMAL TUMORS; TYROSINE KINASE INHIBITOR; STEM-CELL FACTOR; CHRONIC MYELOGENOUS LEUKEMIA; CHRONIC MYELOID-LEUKEMIA; PHASE-II TRIAL; DOSE IMATINIB MESYLATE; PROTOONCOGENE C-KIT; CLINICAL-EFFICACY; METASTATIC MELANOMA AB We have embarked on an exciting era of targeted therapy in oncology, and in many ways a most exciting one for melanoma. Understanding the fundamental genetic changes that govern the development and growth of melanoma has propelled the field forward. Genetic mutations in KIT have proven to be successful targets of several tyrosine kinase inhibitors with demonstrated clinical efficacy in gastrointestinal stromal tumors (GIST). With the identification of mutations and amplifications in KIT in melanomas that occur on acral and mucosal surfaces as well as on skin with chronic sun damage, initial reports of treatment with inhibitors in selected patients have suggested promising clinical activity. In this chapter, we review the biology of KIT and its role in melanoma as well report on the current experience with kinase inhibitors in selected melanoma patient populations. We will also outline the ongoing efforts that strive to answer critical questions on efficacy, dosing, and tumor genomics that predict response and suggest mechanisms of resistance. C1 [Ibrahim, Nageatte; Hodi, F. Stephen] Dana Farber Brigham & Womens Canc Ctr, Dept Med Oncol, Dana Farber Canc Inst, Boston, MA 02115 USA. [Ibrahim, Nageatte; Hodi, F. Stephen] Dana Farber Brigham & Womens Canc Ctr, Melanoma Dis Ctr, Boston, MA USA. RP Hodi, FS (reprint author), Dana Farber Brigham & Womens Canc Ctr, Dept Med Oncol, Dana Farber Canc Inst, Boston, MA 02115 USA. EM stephen_hodi@dfci.harvard.edu NR 85 TC 0 Z9 0 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA BN 978-1-61779-406-3 J9 CURR CLIN ONCOL PY 2012 BP 43 EP 61 DI 10.1007/978-1-61779-407-0_4 D2 10.1007/978-1-61779-407-0 PG 19 WC Oncology SC Oncology GA BZT70 UT WOS:000302922900004 ER PT B AU Chapman, PB Flaherty, K AF Chapman, Paul B. Flaherty, Keith BE Gajewski, TF Hodi, FS TI Targeted Inhibition of B-Raf SO TARGETED THERAPEUTICS IN MELANOMA SE Current Clinical Oncology Series LA English DT Article; Book Chapter DE BRAF; MAPK; Vemurafenib; MEK; PLX4032 ID SIGNAL-REGULATED KINASE; RANDOMIZED PHASE-II; WILD-TYPE BRAF; ADVANCED MELANOMA; METASTATIC MELANOMA; MUTATIONS; CRAF; COMBINATION; SORAFENIB; HETERODIMERIZATION AB The hunt for mutated and activated kinases in cancer has proceeded at an accelerated pace since the successful treatment of chronic myelogenous leukemia with imatinib and with the development of new genomic sequencing technologies. The identification of activating mutations in B-Raf in a major subset of melanomas was first reported in 2002. Basic laboratory experiments confirmed the ability of mutant B-Raf to function as a driver oncogene in vivo. Relatively rapidly, inhibitors that preferentially target the mutated kinase were developed and tested clinically, and these studies revealed that the majority of patients bearing V600E B-Raf mutant melanomas showed a clinical response. Positive results of a randomized phase III clinical trial were released in early 2011. The current phase of this remarkable story is focused upon understanding mechanisms of primary and secondary resistance to B-Raf inhibitors in the clinic. C1 [Chapman, Paul B.] Mem Sloan Kettering Canc Ctr, Dept Med, New York, NY 10021 USA. [Flaherty, Keith] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. RP Chapman, PB (reprint author), Mem Sloan Kettering Canc Ctr, Dept Med, 1275 York Ave, New York, NY 10021 USA. EM chapmanp@mskoc.org NR 45 TC 1 Z9 1 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA BN 978-1-61779-406-3 J9 CURR CLIN ONCOL PY 2012 BP 63 EP 76 DI 10.1007/978-1-61779-407-0_5 D2 10.1007/978-1-61779-407-0 PG 14 WC Oncology SC Oncology GA BZT70 UT WOS:000302922900005 ER PT B AU Singh, A Kim, M AF Singh, Anuradha Kim, Minjee BA Singh, A BF Singh, A TI Periods of Confusion, Agitation, and Disorientation SO CASE-BASED NEUROLOGY LA English DT Article; Book Chapter ID STATUS EPILEPTICUS C1 [Singh, Anuradha] NYU, Dept Neurol, Langone Med Ctr, New York, NY 10016 USA. [Kim, Minjee] Massachusetts Gen Hosp, Dept Neurol, Harvard Univ Residency Program, Boston, MA 02114 USA. [Kim, Minjee] Brigham & Womens Hosp, Boston, MA 02115 USA. RP Singh, A (reprint author), NYU, Dept Neurol, Langone Med Ctr, New York, NY 10016 USA. NR 6 TC 0 Z9 0 U1 0 U2 0 PU DEMOS MEDICAL PUBLICATIONS PI NEW YORK PA 11 WEST 42ND STREET, 15TH FLOOR, NEW YORK, NY 10036 USA BN 978-1-933864-25-9 PY 2012 BP 357 EP 364 PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA BYM57 UT WOS:000299358800049 ER PT B AU Fan, VS Giardino, ND AF Fan, Vincent S. Giardino, Nicholas D. BE Nici, L Wallack, RZ TI Anxiety and Depression SO CHRONIC OBSTRUCTIVE PULMONARY DISEASE: CO-MORBIDITIES AND SYSTEMIC CONSEQUENCES SE Respiratory Medicine Series LA English DT Article; Book Chapter DE Depression; Anxiety; COPD; Comorbidity; Quality of life; Exacerbation; Mortality; Diagnosis; Medication; Pharmacotherapy; Treatment ID OBSTRUCTIVE PULMONARY-DISEASE; QUALITY-OF-LIFE; C-REACTIVE PROTEIN; RANDOMIZED CONTROLLED-TRIAL; CORONARY-HEART-DISEASE; COGNITIVE-BEHAVIORAL THERAPY; INTERFERON-ALPHA THERAPY; COPD PATIENTS; MAJOR DEPRESSION; FUNCTIONAL STATUS AB Increasing evidence suggests that depression and anxiety are important comorbidities in COPD, and are associated with a number of adverse outcomes including worse health-related quality of life, an increased risk of exacerbations, and a higher mortality. The burden of depression in COPD is higher than in the general population, and many patients remain undiagnosed. Although treatment of depression and anxiety may include medications or pharmacotherapy, many patients with depressive symptoms do not receive treatment. C1 [Fan, Vincent S.] Univ Washington, Sch Med, Dept Med, VA Puget Sound Hlth Care Syst, Seattle, WA 98195 USA. [Giardino, Nicholas D.] Univ Michigan, Dept Psychiat, VA Ann Arbor Healthcare Syst, Ann Arbor, MI 48109 USA. RP Fan, VS (reprint author), Univ Washington, Sch Med, Dept Med, VA Puget Sound Hlth Care Syst, Seattle, WA 98195 USA. EM Vincent.Fan@va.gov; ngiardin@med.umich.edu NR 144 TC 1 Z9 1 U1 0 U2 1 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA BN 978-1-60761-672-6 J9 RESPIR MED SER PY 2012 BP 95 EP 118 DI 10.1007/978-1-60761-673-3_7 D2 10.1007/978-1-60761-673-3 PG 24 WC Cardiac & Cardiovascular Systems; Medicine, General & Internal SC Cardiovascular System & Cardiology; General & Internal Medicine GA BZD38 UT WOS:000301157200007 ER PT J AU Soskin, DP Carl, JR Alpert, J Fava, M AF Soskin, David P. Carl, Jenna R. Alpert, Jonathan Fava, Maurizio TI Antidepressant Effects on Emotional Temperament: Toward a Biobehavioral Research Paradigm for Major Depressive Disorder SO CNS NEUROSCIENCE & THERAPEUTICS LA English DT Review DE Combined cognitive-behavioral and pharmacological treatment; Dopamine and the reward system; Emotional temperament; Major depressive disorder ID SEROTONIN REUPTAKE INHIBITORS; DSM-IV ANXIETY; STAR-ASTERISK-D; SELECTIVE SEROTONIN; MOOD DISORDERS; NEGATIVE AFFECT; DOUBLE-BLIND; STRUCTURAL RELATIONSHIPS; BEHAVIORAL ACTIVATION; PERSONALITY-TRAITS AB Background: Given the limited efficacy of current pharmacotherapy for major depressive disorder (MDD) and the historical decline in antidepressant development, there is increasing clinical urgency to develop more effective treatments. Objectives: To synthesize findings from clinical psychology and affective neuroscience related to the construct of emotional temperament; to examine the effects of antidepressants on the temperament dimensions of positive (PA) and negative affectivity (NA); and to propose a biobehavioral research paradigm for the treatment of MDD. Methods: We begin with an introduction to PA and NA, which emphasizes their construct development, historical context, and relevance to psychopathology. We then review studies of antidepressant effects on PA and NA, and explore two related hypotheses: (1) Cause-correction: The antidepressant response may fundamentally occur through changes in emotional temperament, with subsequent spread to syndrome or symptom changes; (2) preferential effects: Antidepressants with different mechanisms of action may have preferential effects on PA or NA. Results: Preliminary findings appear to support the cause-correction hypothesis; there is insufficient clinical evidence to support the preferential effects hypothesis. Conclusions: PA and NA are biologically based temperament dimensions, which modulate emotional, motivational, and behavioral responses to positive and negative incentives. They can be altered by antidepressants, and may independently contribute to depression improvement. In addition, the distinct biobehavioral features of PA and NA suggest that combined pharmacological and cognitivebehavioral treatments targeting these dimensions may have specific, and perhaps, synergistic antidepressant effects. C1 [Soskin, David P.; Alpert, Jonathan; Fava, Maurizio] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Depress Clin & Res Program, Boston, MA 02114 USA. [Carl, Jenna R.] Boston Univ, Ctr Anxiety & Related Disorders, Boston, MA 02215 USA. RP Soskin, DP (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Depress Clin & Res Program, 1 Bowdoin Sq,6th Floor, Boston, MA 02114 USA. EM dsoskin@partners.org OI Alpert, Jonathan/0000-0002-4332-908X FU Abbott Laboratories; Alkermes; Lichtwer Pharma GmbH; Lorex Pharmaceuticals; Aspect Medical Systems; Astra-Zeneca; Bristol-Myers Squibb Company; Cephalon; Cyberonics; Eli Lilly Company; Forest Pharmaceuticals Inc.; GlaxoSmithkline; J & J Pharmaceuticals; Novartis; Organon Inc.; PamLab, LLC; Pfizer Inc; Pharmavite; Roche; Sanofi/Synthelabo; Solvay Pharmaceuticals, Inc.; Wyeth-Ayerst Laboratories; Belvoir Publishing; Abbot Laboratasuories; Alkermes, Inc.; AstraZeneca; BioResearch; BrainCells Inc.; Bristol-Myers Squibb; CeNeRx BioPharma; Clinical Trials Solutions, LLC; Clintara, LLC; Covance; Covidien; Eli Lilly and Company; EnVivo Pharmaceuticals, Inc.; Euthymics Bioscience, Inc.; Forest Pharmaceuticals, Inc.; Ganeden Biotech, Inc.; Icon Clinical Research; i3 Innovus/Ingenix; Johnson & Johnson Pharmaceutical Research Development; National Alliance for Research on Schizophrenia & Depression (NARSAD); National Center for Complementary and Alternative Medicine (NCCAM); National Institute of Drug Abuse (NIDA); National Institute of Mental Health (NIMH); Novartis AG; Organon Pharmaceuticals; PamLab, LLC.; Pfizer Inc.; Pharmavite(R) LLC; Photothera; Roche Pharmaceuticals; RCT Logic, LLC; Sanofi-Aventis US LLC; Shire; Synthelabo FX Dr. Jonathan Alpert has received research support from: Abbott Laboratories, Alkermes, Lichtwer Pharma GmbH, Lorex Pharmaceuticals; Aspect Medical Systems, Astra-Zeneca, Bristol-Myers Squibb Company, Cephalon, Cyberonics, Eli Lilly & Company, Forest Pharmaceuticals Inc., GlaxoSmithkline, J & J Pharmaceuticals, Novartis, Organon Inc., PamLab, LLC, Pfizer Inc, Pharmavite, Roche, Sanofi/Synthelabo, Solvay Pharmaceuticals, Inc., and Wyeth-Ayerst Laboratories. Dr. Jonathan Alpert has participated on advisory boards for or consulted to: Eli Lilly & Company, Pamlab LLC, and Pharmavite LLC. Dr. Jonathan Alpert has received speakers' honoraria from: Eli Lilly & Company, Xian-Janssen, Organon, MGH Psychiatry Academy, Reed Medical Education and Primedia, and the American Psychiatric Association and has received editorial fees from Belvoir Publishing.; Dr. Maurizio Fava has received research support from: Abbot Laboratasuories; Alkermes, Inc.; Aspect Medical Systems; AstraZeneca; BioResearch; BrainCells Inc.; Bristol-Myers Squibb; CeNeRx BioPharma; Cephalon; Clinical Trials Solutions, LLC; Clintara, LLC; Covance; Covidien; Eli Lilly and Company; EnVivo Pharmaceuticals, Inc.; Euthymics Bioscience, Inc.; Forest Pharmaceuticals, Inc.; Ganeden Biotech, Inc.; GlaxoSmithKline; Icon Clinical Research; i3 Innovus/Ingenix; Johnson & Johnson Pharmaceutical Research & Development; Lichtwer Pharma GmbH; Lorex Pharmaceuticals; National Alliance for Research on Schizophrenia & Depression (NARSAD); National Center for Complementary and Alternative Medicine (NCCAM); National Institute of Drug Abuse (NIDA); National Institute of Mental Health (NIMH); Novartis AG; Organon Pharmaceuticals; PamLab, LLC.; Pfizer Inc.; Pharmavite (R) LLC; Photothera; Roche Pharmaceuticals; RCT Logic, LLC; Sanofi-Aventis US LLC; Shire; Solvay Pharmaceuticals, Inc.; Synthelabo; Wyeth-Ayerst Laboratories. NR 89 TC 12 Z9 12 U1 5 U2 22 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1755-5930 EI 1755-5949 J9 CNS NEUROSCI THER JI CNS Neurosci. Ther. PY 2012 VL 18 IS 6 BP 441 EP 451 DI 10.1111/j.1755-5949.2012.00318.x PG 11 WC Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA 952AR UT WOS:000304762600002 PM 22672296 ER PT J AU Rigotti, NA Clair, C Munafo, MR Stead, LF AF Rigotti, Nancy A. Clair, Carole Munafo, Marcus R. Stead, Lindsay F. TI Interventions for smoking cessation in hospitalised patients SO COCHRANE DATABASE OF SYSTEMATIC REVIEWS LA English DT Review DE Hospitalization; Patient Education as Topic; Randomized Controlled Trials as Topic; Sensitivity and Specificity; Smoking [prevention & control]; Smoking Cessation [methods]; Humans ID RANDOMIZED CONTROLLED-TRIAL; CORONARY-HEART-DISEASE; NICOTINE REPLACEMENT THERAPY; ACUTE MYOCARDIAL-INFARCTION; OBSTRUCTIVE PULMONARY-DISEASE; FOLLOW-UP INTERVENTION; BYPASS GRAFT-SURGERY; QUALITY-OF-LIFE; CARDIOVASCULAR-DISEASE; NONSMOKING WINS AB Background Smoking contributes to reasons for hospitalisation, and the period of hospitalisation may be a good time to provide help with quitting. Objectives To determine the effectiveness of interventions for smoking cessation that are initiated for hospitalised patients. Search methods We searched the Cochrane Tobacco Addiction Group register which includes papers identified from CENTRAL, MEDLINE, EMBASE and PsycINFO in December 2011 for studies of interventions for smoking cessation in hospitalised patients, using terms including (hospital and patient*) or hospitali* or inpatient* or admission* or admitted. Selection criteria Randomized and quasi-randomized trials of behavioural, pharmacological or multicomponent interventions to help patients stop smoking, conducted with hospitalised patients who were current smokers or recent quitters (defined as having quit more than one month before hospital admission). The intervention had to start in the hospital but could continue after hospital discharge. We excluded studies of patients admitted to facilities that primarily treat psychiatric disorders or substance abuse, studies that did not report abstinence rates and studies with follow-up of less than six months. Both acute care hospitals and rehabilitation hospitals were included in this update, with separate analyses done for each type of hospital. Data collection and analysis Two authors extracted data independently for each paper, with disagreements resolved by consensus. Main results Fifty trials met the inclusion criteria. Intensive counselling interventions that began during the hospital stay and continued with supportive contacts for at least one month after discharge increased smoking cessation rates after discharge (risk ratio (RR) 1.37, 95% confidence interval (CI) 1.27 to 1.48; 25 trials). A specific benefit for post-discharge contact compared with usual care was found in a subset of trials in which all participants received a counselling intervention in the hospital and were randomly assigned to post-discharge contact or usual care. No statistically significant benefit was found for less intensive counselling interventions. Adding nicotine replacement therapy (NRT) to an intensive counselling intervention increased smoking cessation rates compared with intensive counselling alone (RR 1.54, 95% CI 1.34 to 1.79, six trials). Adding varenicline to intensive counselling had a non-significant effect in two trials (RR 1.28, 95% CI 0.95 to 1.74). Adding bupropion did not produce a statistically significant increase in cessation over intensive counselling alone (RR 1.04, 95% CI 0.75 to 1.45, three trials). A similar pattern of results was observed in a subgroup of smokers admitted to hospital because of cardiovascular disease (CVD). In this subgroup, intensive intervention with follow-up support increased the rate of smoking cessation (RR 1.42, 95% CI 1.29 to 1.56), but less intensive interventions did not. One trial of intensive intervention including counselling and pharmacotherapy for smokers admitted with CVD assessed clinical and health care utilization endpoints, and found significant reductions in all-cause mortality and hospital readmission rates over a two-year follow-up period. These trials were all conducted in acute care hospitals. A comparable increase in smoking cessation rates was observed in a separate pooled analysis of intensive counselling interventions in rehabilitation hospitals (RR 1.71, 95% CI 1.37 to 2.14, three trials). Authors' conclusions High intensity behavioural interventions that begin during a hospital stay and include at least one month of supportive contact after discharge promote smoking cessation among hospitalised patients. The effect of these interventions was independent of the patient's admitting diagnosis and was found in rehabilitation settings as well as acute care hospitals. There was no evidence of effect for interventions of lower intensity or shorter duration. This update found that adding NRT to intensive counselling significantly increases cessation rates over counselling alone. There is insufficient direct evidence to conclude that adding bupropion or varenicline to intensive counselling increases cessation rates over what is achieved by counselling alone. C1 [Rigotti, Nancy A.] Massachusetts Gen Hosp, Tobacco Res & Treatment Ctr, Dept Med, Boston, MA 02114 USA. [Rigotti, Nancy A.; Clair, Carole] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Clair, Carole] Univ Lausanne, Dept Ambulatory Care & Community Med, Lausanne, Switzerland. [Munafo, Marcus R.] Univ Bristol, Dept Expt Psychol, Bristol, Avon, England. [Stead, Lindsay F.] Univ Oxford, Dept Primary Care Hlth Sci, Oxford, England. RP Rigotti, NA (reprint author), Massachusetts Gen Hosp, Tobacco Res & Treatment Ctr, Dept Med, S50-9, Boston, MA 02114 USA. EM nrigotti@partners.org RI Clair, Carole/D-9786-2014; OI Clair, Carole/0000-0001-5281-0943; Munafo, Marcus/0000-0002-4049-993X FU U.S. National Institutes of Health; private nonprofit foundations; U.S. National Heart Lung and Blood Institute; Pfizer; Department of Primary Health Care, Oxford University, UK; NHS, UK; NIH / NHLBI, USA [K24-044440] FX Dr Rigotti was the co-author of three studies included in the review. Dr. Rigotti's research is funded by the U.S. National Institutes of Health, by private nonprofit foundations, and by the pharmaceutical companies that make investigational or approved smoking cessation products. Her work on this review was funded by a Midcareer Investigator Award in Patient-Oriented Research from the U.S. National Heart Lung and Blood Institute. Marcus Munaf has received grant funding from Pfizer through their Investigator Initiated Research programme.; Internal sources; Department of Primary Health Care, Oxford University, UK.; External sources; NHS Research and Development Programme, UK.; NIH / NHLBI Mid-career Investigator Award in Patient Oriented Research (#K24-044440), USA. NR 169 TC 60 Z9 60 U1 2 U2 29 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1469-493X J9 COCHRANE DB SYST REV JI Cochrane Database Syst Rev. PY 2012 IS 5 AR CD001837 DI 10.1002/14651858.CD001837.pub3 PG 87 WC Medicine, General & Internal SC General & Internal Medicine GA 943CU UT WOS:000304098900006 PM 22592676 ER PT J AU Chung, YSA Kocks, C AF Chung, Yoon-Suk Alexander Kocks, Christine TI Phagocytosis of bacterial pathogens SO FLY LA English DT Article DE innate immunity; phagocytosis; antimicrobial peptides; phagocytic receptor; Eater; cecropin A; lysozyme; Gram-negative bacteria; pattern recognition; pattern recognition receptor ID CATIONIC ANTIMICROBIAL PEPTIDES; MOUSE LYSOZYME-M; PSEUDOMONAS-AERUGINOSA; IMMUNE-RESPONSE; DROSOPHILA-MELANOGASTER; SCAVENGER RECEPTORS; OUTER-MEMBRANE; HOST-DEFENSE; INFECTION; PLASMATOCYTES AB Phagocytosis is an evolutionarily ancient, receptor-driven process, by which phagocytic cells recognize invading microbes and destroy them after internalization. The phagocytosis receptor Eater is expressed exclusively on Drosophila phagocytes and is required for the survival of bacterial infections. In a recent study, we explored how Eater can defend fruit flies against different kinds of bacteria. We discovered that Eater bound to certain types of bacteria directly, while for others bacterial binding was dependent on prior disruption of the bacterial envelope. Similar to phagocytes, antimicrobial peptides and lysozymes are ancient components of animal immune systems. Our results suggest that cationic antimicrobial peptides, as well as lysozymes, can facilitate Eater binding to live Gram-negative bacteria. Both types of molecules promote surface-exposure of bacterial ligands that otherwise would remain buried and hidden under an outer membrane. We propose that unmasking ligands for phagocytic receptors may be a conserved mechanism operating in many animals, including humans. Thus, studying a Drosophila phagocytosis receptor may advance our understanding of innate immunity in general. C1 [Chung, Yoon-Suk Alexander; Kocks, Christine] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pediat, Boston, MA 02114 USA. [Chung, Yoon-Suk Alexander; Kocks, Christine] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Mol Biol, Boston, MA USA. RP Kocks, C (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pediat, Boston, MA 02114 USA. EM kocks@molbio.mgh.harvard.edu FU NIH/NIAID [P01 AI44220]; Ausubel laboratory; Department of Molecular Biology; NIH Center for the Study of Inflammatory Bowel Disease [DK43351]; Boston Area Diabetes and Endocrinology Research Center [DK57521] FX We gratefully acknowledge funding by NIH/NIAID through grant P01 AI44220. We thank Janice Lee for expert technical help and our colleagues in the Ausubel laboratory and the Department of Molecular Biology for support, in particular Julia Dewdney and Yuval Tabach for advice with microarray analysis and Read Pukkila-Worley for comments on the manuscript. EM was performed by Mary McKee, Microscopy Core, Center for Systems Biology/Program in Membrane Biology, which is partially supported by NIH Center for the Study of Inflammatory Bowel Disease Grant DK43351 and Boston Area Diabetes and Endocrinology Research Center Award DK57521. NR 36 TC 4 Z9 4 U1 2 U2 9 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 1933-6934 J9 FLY JI Fly PD JAN-MAR PY 2012 VL 6 IS 1 BP 21 EP 25 DI 10.4161/fly.18497 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 947FD UT WOS:000304412700004 PM 22223092 ER PT J AU Brun, R Kuo, B AF Brun, Rita Kuo, Braden BE Parkman, HP McCallum, RW TI Wireless Motility Capsule in Gastroparesis SO GASTROPARESIS: PATHOPHYSIOLOGY, PRESENTATION AND TREATMENT SE Clinical Gastroenterology LA English DT Article; Book Chapter DE Capsule technology; Gastrointestinal tract; Gastrointestinal transit; Electronic radiotelemetry capsule ID GASTRIC-MOTILITY; PH; RADIOTELEMETRY; SCINTIGRAPHY; SMARTPILL; TRANSIT C1 [Kuo, Braden] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastrointestinal Unit,GI Motil Lab, Boston, MA 02114 USA. RP Kuo, B (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastrointestinal Unit,GI Motil Lab, Boston, MA 02114 USA. EM bkuo@partners.org NR 18 TC 0 Z9 0 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA BN 978-1-60761-552-1 J9 CLIN GASTROENT-SER PY 2012 BP 113 EP 121 DI 10.1007/978-1-60761-552-1_10 D2 10.1007/978-1-60761-552-1 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA BZJ09 UT WOS:000301749900010 ER PT J AU Schaid, DJ Sinnwell, JP Jenkins, GD McDonnell, SK Ingle, JN Kubo, M Goss, PE Costantino, JP Wickerham, DL Weinshilboum, RM AF Schaid, Daniel J. Sinnwell, Jason P. Jenkins, Gregory D. McDonnell, Shannon K. Ingle, James N. Kubo, Michiaki Goss, Paul E. Costantino, Joseph P. Wickerham, D. Lawrence Weinshilboum, Richard M. TI Using the Gene Ontology to Scan Multilevel Gene Sets for Associations in Genome Wide Association Studies SO GENETIC EPIDEMIOLOGY LA English DT Article DE gene-sets; genome wide association; pathways; score statistics ID PRINCIPAL-COMPONENTS; PATHWAY ANALYSIS; LINKAGE DISEQUILIBRIUM; MISSING HERITABILITY; LOGISTIC-REGRESSION; COMPLEX DISEASES; BREAST-CANCER; MULTIPLE SNPS; TAMOXIFEN; REGION AB Gene-set analyses have been widely used in gene expression studies, and some of the developed methods have been extended to genome wide association studies (GWAS). Yet, complications due to linkage disequilibrium (LD) among single nucleotide polymorphisms (SNPs), and variable numbers of SNPs per gene and genes per gene-set, have plagued current approaches, often leading to ad hoc "fixes.'' To overcome some of the current limitations, we developed a general approach to scan GWAS SNP data for both gene-level and gene-set analyses, building on score statistics for generalized linear models, and taking advantage of the directed acyclic graph structure of the gene ontology when creating gene-sets. However, other types of gene-set structures can be used, such as the popular Kyoto Encyclopedia of Genes and Genomes (KEGG). Our approach combines SNPs into genes, and genes into gene-sets, but assures that positive and negative effects of genes on a trait do not cancel. To control for multiple testing of many gene-sets, we use an efficient computational strategy that accounts for LD and provides accurate step-down adjusted P-values for each gene-set. Application of our methods to two different GWAS provide guidance on the potential strengths and weaknesses of our proposed gene-set analyses. Genet. Epidemiol. 36 : 3-16, 2012. (C) 2011 Wiley Periodicals, Inc. C1 [Schaid, Daniel J.; Sinnwell, Jason P.; Jenkins, Gregory D.; McDonnell, Shannon K.] Mayo Clin, Dept Hlth Sci Res, Div Biomed Stat & Informat, Rochester, MN 55905 USA. [Ingle, James N.] Mayo Clin, Dept Oncol, Div Med Oncol, Rochester, MN 55905 USA. [Weinshilboum, Richard M.] Mayo Clin, Dept Mol Pharmacol & Expt Therapeut, Div Clin Pharmacol, Rochester, MN 55905 USA. [Kubo, Michiaki] RIKEN Ctr Genom Med, Tokyo, Japan. [Goss, Paul E.] Harvard Univ, Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Costantino, Joseph P.] Univ Pittsburgh, Dept Biostat, Pittsburgh, PA 15261 USA. [Wickerham, D. Lawrence] Allegheny Gen Hosp, Sect Canc Genet & Prevent, Pittsburgh, PA 15212 USA. RP Schaid, DJ (reprint author), Mayo Clin, Div Biostat, Harwick 7,200 1st St SW, Rochester, MN 55905 USA. EM schaid@mayo.edu RI Kubo, Michiaki/N-7947-2015 FU National Institutes of Health [GM065450, U10-CA-37377, U10-CA-69974, U01GM61388, U01GM63173, P50CA116201, U10CA77202, U19 GM6138]; National Cancer Institute of Canada [CCS 015469]; Ministry of Education, Culture, Sports, Science and Technology, Japan; U.S. Public Health Service, National Institutes of Health (NIH) [GM065450] FX Contract grant sponsor: National Institutes of Health; Contract grant numbers: GM065450; U10-CA-37377; U10-CA-69974; U01GM61388; U01GM63173; P50CA116201; U10CA77202; U19 GM6138; Contract grant sponsor: National Cancer Institute of Canada; Contract grant number: CCS 015469; Contract grant sponsor: Ministry of Education, Culture, Sports, Science and Technology, Japan.; This research was supported by the U.S. Public Health Service, National Institutes of Health (NIH), contract grant number GM065450 (D.J.S., J.P.S.). The NSABP trials were supported by NIH contract grant numbers U10-CA-37377 and U10-CA-69974. The MA.27 trail was supported by NIH contract grant numbers U01GM61388, U01GM63173, P50CA116201, U10CA77202, and the National Cancer Institute of Canada contract grant number CCS 015469. The administrative coordination and data analyses were supported by NIH contract number U19 GM6138 (Mayo PGRN). The genotyping was supported the Biobank Japan Project funded by the Ministry of Education, Culture, Sports, Science and Technology, Japan. Genotyping was performed at the RIKEN Center for Genomic Medicine, Japan. NR 58 TC 15 Z9 16 U1 0 U2 15 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0741-0395 J9 GENET EPIDEMIOL JI Genet. Epidemiol. PD JAN PY 2012 VL 36 IS 1 BP 3 EP 16 DI 10.1002/gepi.20632 PG 14 WC Genetics & Heredity; Mathematical & Computational Biology SC Genetics & Heredity; Mathematical & Computational Biology GA 918JB UT WOS:000302244400002 PM 22161999 ER PT B AU Murphy, JE Ryan, DP AF Murphy, Janet E. Ryan, David P. BE Mueller, PR Adam, A TI Principles of Medical Oncology and Chemotherapy SO INTERVENTIONAL ONCOLOGY: A PRACTICAL GUIDE FOR THE INTERVENTIONAL RADIOLOGIST LA English DT Article; Book Chapter ID CELL LUNG-CANCER; ADVANCED HEPATOCELLULAR-CARCINOMA; CLINICAL-PRACTICE GUIDELINES; BREAST-CANCER; PHASE-II; INTERFERON-ALPHA; RANDOMIZED-TRIAL; RECTAL-CANCER; DOXORUBICIN; SURVIVAL C1 [Murphy, Janet E.; Ryan, David P.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Canc, Boston, MA 02114 USA. [Ryan, David P.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. RP Murphy, JE (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Canc, 55 Fruit St,Yawkey 7E, Boston, MA 02114 USA. EM jemurphy@partners.org NR 41 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 978-1-4419-1468-2 PY 2012 BP 3 EP 13 DI 10.1007/978-1-4419-1469-9_1 D2 10.1007/978-1-4419-1469-9 PG 11 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA BYP66 UT WOS:000299651300001 ER PT B AU Hong, TS AF Hong, Theodore S. BE Mueller, PR Adam, A TI Modern Radiation Therapy Approaches: Targeted and Ablative Strategies SO INTERVENTIONAL ONCOLOGY: A PRACTICAL GUIDE FOR THE INTERVENTIONAL RADIOLOGIST LA English DT Article; Book Chapter ID PROTON-BEAM THERAPY; 3-DIMENSIONAL CONFORMAL RADIOTHERAPY; STEREOTACTIC BODY RADIOTHERAPY; INDUCED LIVER-DISEASE; STAGE LUNG-CANCER; HEPATOCELLULAR-CARCINOMA; PHASE-II; PANCREATIC-CANCER; METASTASES; TRIAL C1 Massachusetts Gen Hosp, Dept Radiat Oncol, Gastrointestinal Serv, Boston, MA 02114 USA. RP Hong, TS (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Gastrointestinal Serv, 100 Blossom St, Boston, MA 02114 USA. EM tshong1@partners.org NR 29 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 978-1-4419-1468-2 PY 2012 BP 15 EP 22 DI 10.1007/978-1-4419-1469-9_2 D2 10.1007/978-1-4419-1469-9 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA BYP66 UT WOS:000299651300002 ER PT B AU Thabet, A Gervais, DA AF Thabet, Ashraf Gervais, Debra A. BE Mueller, PR Adam, A TI The Role of Diagnostic Imaging in the Planning and Evaluation of Ablation Techniques SO INTERVENTIONAL ONCOLOGY: A PRACTICAL GUIDE FOR THE INTERVENTIONAL RADIOLOGIST LA English DT Article; Book Chapter ID PERCUTANEOUS RADIOFREQUENCY ABLATION; RENAL-CELL CARCINOMA; UNRESECTABLE LUNG-TUMORS; HEPATOCELLULAR-CARCINOMA; THERMAL ABLATION; HEPATIC-TUMORS; FOLLOW-UP; LIVER-TRANSPLANTATION; SINGLE-INSTITUTION; PART I C1 [Thabet, Ashraf; Gervais, Debra A.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Thabet, A (reprint author), Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. EM athabet@partners.org NR 52 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 978-1-4419-1468-2 PY 2012 BP 65 EP 79 DI 10.1007/978-1-4419-1469-9_6 D2 10.1007/978-1-4419-1469-9 PG 15 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA BYP66 UT WOS:000299651300006 ER PT B AU Psutka, SP Eisner, BH AF Psutka, Sarah P. Eisner, Brian H. BE Mueller, PR Adam, A TI Nonradiological Treatment for Renal Tumors SO INTERVENTIONAL ONCOLOGY: A PRACTICAL GUIDE FOR THE INTERVENTIONAL RADIOLOGIST LA English DT Article; Book Chapter ID LAPAROSCOPIC RADICAL NEPHRECTOMY; LYMPH-NODE DISSECTION; NEPHRON-SPARING SURGERY; CELL-CARCINOMA; CYTOREDUCTIVE NEPHRECTOMY; SURVIVAL; CANCER; INVOLVEMENT; EXPERIENCE; MANAGEMENT C1 [Psutka, Sarah P.; Eisner, Brian H.] Massachusetts Gen Hosp, Dept Urol, Boston, MA 02114 USA. RP Psutka, SP (reprint author), Massachusetts Gen Hosp, Dept Urol, PGY 4, Boston, MA 02114 USA. EM spsutka@partners.org NR 46 TC 1 Z9 1 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 978-1-4419-1468-2 PY 2012 BP 119 EP 125 DI 10.1007/978-1-4419-1469-9_11 D2 10.1007/978-1-4419-1469-9 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA BYP66 UT WOS:000299651300011 ER PT B AU Oklu, R Kalva, SP AF Oklu, Rahmi Kalva, Sanjeeva P. BE Mueller, PR Adam, A TI Embolotherapy for Renal Tumors SO INTERVENTIONAL ONCOLOGY: A PRACTICAL GUIDE FOR THE INTERVENTIONAL RADIOLOGIST LA English DT Article; Book Chapter ID TERM-FOLLOW-UP; CELL-CARCINOMA; ARTERIAL EMBOLIZATION; SURGICAL-MANAGEMENT; ANGIOMYOLIPOMAS; COMPLICATIONS; NEPHRECTOMY; EXPERIENCE; HEMORRHAGE; THROMBUS C1 [Oklu, Rahmi; Kalva, Sanjeeva P.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Vasc Imaging & Intervent,Dept Imaging, Boston, MA 02115 USA. RP Kalva, SP (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Vasc Imaging & Intervent,Dept Imaging, Boston, MA 02115 USA. EM skalva@partners.org NR 19 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 978-1-4419-1468-2 PY 2012 BP 127 EP 130 DI 10.1007/978-1-4419-1469-9_12 D2 10.1007/978-1-4419-1469-9 PG 4 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA BYP66 UT WOS:000299651300012 ER PT J AU Winey, B Daartz, J Dankers, F Bussiere, M AF Winey, Brian Daartz, Juliane Dankers, Frank Bussiere, Marc TI Immobilization precision of a modified GTC frame SO JOURNAL OF APPLIED CLINICAL MEDICAL PHYSICS LA English DT Article DE stereotactic radiosurgery; immobilization; patient setup ID FRACTIONATED STEREOTACTIC RADIOTHERAPY; ACCURACY; HEAD AB The purpose of this study was to evaluate and quantify the interfraction reproducibility and intrafraction immobilization precision of a modified GTC frame. The error of the patient alignment and imaging systems were measured using a cranial skull phantom, with simulated, predetermined shifts. The kV setup images were acquired with a room-mounted set of kV sources and panels. Calculated translations and rotations provided by the computer alignment software relying upon three implanted fiducials were compared to the known shifts, and the accuracy of the imaging and positioning systems was calculated. Orthogonal kV setup images for 45 proton SRT patients and 1002 fractions (average 22.3 fractions/patient) were analyzed for interfraction and intrafraction immobilization precision using a modified GTC frame. The modified frame employs a radiotransparent carbon cup and molded pillow to allow for more treatment angles from posterior directions for cranial lesions. Patients and the phantom were aligned with three 1.5 mm stainless steel fiducials implanted into the skull. The accuracy and variance of the patient positioning and imaging systems were measured to be 0.10 +/- 0.06 mm, with the maximum uncertainty of rotation being +/- 0.07 degrees. 957 pairs of interfraction image sets and 974 intrafraction image sets were analyzed. 3D translations and rotations were recorded. The 3D vector interfraction setup reproducibility was 0.13 mm +/- 1.8 mm for translations and the largest uncertainty of +/- 1.07 degrees for rotations. The intrafraction immobilization efficacy was 0.19 mm +/- 0.66 mm for translations and the largest uncertainty of +/- 0.50 degrees for rotations. The modified GTC frame provides reproducible setup and effective intrafraction immobilization, while allowing for the complete range of entrance angles from the posterior direction. C1 [Winey, Brian] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol,FH Burr Proton Therapy Ctr, Boston, MA 02114 USA. [Winey, Brian; Bussiere, Marc] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Daartz, Juliane] Paul Scherrer Inst, Dept Radiat Oncol, CH-5232 Villigen, Switzerland. [Dankers, Frank] Eindhoven Univ Technol, Dept Appl Phys, NL-5600 MB Eindhoven, Netherlands. RP Winey, B (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol,FH Burr Proton Therapy Ctr, 55 Fruit St, Boston, MA 02114 USA. EM winey.brian@mgh.harvard.edu NR 13 TC 0 Z9 0 U1 0 U2 2 PU MULTIMED INC PI TORONTO PA 66 MARTIN ST, TORONTO, ON L9T 2R2, CANADA SN 1526-9914 J9 J APPL CLIN MED PHYS JI J. Appl. Clin. Med. Phys PY 2012 VL 13 IS 3 BP 12 EP 19 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 943QX UT WOS:000304141400002 ER PT J AU Ng, SK Zygmanski, P Jeung, A Mostafavi, H Hesser, J Bellon, JR Wong, JS Lyatskaya, Y AF Ng, Sook Kien Zygmanski, Piotr Jeung, Andrew Mostafavi, Hassan Hesser, Juergen Bellon, Jennifer R. Wong, Julia S. Lyatskaya, Yulia TI Optimal parameters for clinical implementation of breast cancer patient setup using Varian DTS software SO JOURNAL OF APPLIED CLINICAL MEDICAL PHYSICS LA English DT Article DE digital tomosynthesis; patient setup; shift-and-add algorithm; triangulation ID CONE-BEAM CT; DIGITAL TOMOSYNTHESIS DTS; SURGICAL CLIPS; ANTHROPOMORPHIC PHANTOM; COMPUTED-TOMOGRAPHY; IMAGE REGISTRATION; LUMPECTOMY CAVITY; IRRADIATION; LOCALIZATION; TARGET AB Digital tomosynthesis (DTS) was evaluated as an alternative to cone-beam computed tomography (CBCT) for patient setup. DTS is preferable when there are constraints with setup time, gantry-couch clearance, and imaging dose using CBCT. This study characterizes DTS data acquisition and registration parameters for the setup of breast cancer patients using nonclinical Varian DTS software. DTS images were reconstructed from CBCT projections acquired on phantoms and patients with surgical clips in the target volume. A shift-and-add algorithm was used for DTS volume reconstructions, while automated cross-correlation matches were performed within Varian DTS software. Triangulation on two short DTS arcs separated by various angular spread was done to improve 3D registration accuracy. Software performance was evaluated on two phantoms and ten breast cancer patients using the registration result as an accuracy measure; investigated parameters included arc lengths, arc orientations, angular separation between two arcs, reconstruction slice spacing, and number of arcs. The shifts determined from DTS-to-CT registration were compared to the shifts based on CBCT-to-CT registration. The difference between these shifts was used to evaluate the software accuracy. After findings were quantified, optimal parameters for the clinical use of DTS technique were determined. It was determined that at least two arcs were necessary for accurate 3D registration for patient setup. Registration accuracy of 2 mm was achieved when the reconstruction arc length was > 5 degrees for clips with HU >= 1000; larger arc length (>= 8 degrees) was required for very low HU clips. An optimal arc separation was found to be >= 20 degrees and optimal arc length was 10. Registration accuracy did not depend on DTS slice spacing. DTS image reconstruction took 10-30 degrees seconds and registration took less than 20 seconds. The performance of Varian DTS software was found suitable for the accurate setup of breast cancer patients. Optimal data acquisition and registration parameters were determined. C1 [Ng, Sook Kien; Zygmanski, Piotr; Bellon, Jennifer R.; Wong, Julia S.; Lyatskaya, Yulia] Brigham & Womens Hosp, Dept Radiat Oncol, Boston, MA 02115 USA. [Ng, Sook Kien] Harvard Univ, Sch Med, Dana Faber Canc Inst, Boston, MA 02115 USA. [Ng, Sook Kien; Hesser, Juergen] Univ Heidelberg, Mannheim Med Ctr, Dept Radiat Oncol, D-6800 Mannheim, Germany. [Jeung, Andrew; Mostafavi, Hassan] Varian Med Syst Inc, Palo Alto, CA 94304 USA. RP Ng, SK (reprint author), Brigham & Womens Hosp, Dept Radiat Oncol, 75 Francis St,ASBI L2, Boston, MA 02115 USA. EM Sook_Ng@DFCI.HARVARD.EDU; pzygmanski@lroc.harvard.edu FU Varian Medical Systems Inc.; Kaye Scholars Grant FX This research was funded in part by a grant from Varian Medical Systems Inc. and a Kaye Scholars Grant. NR 28 TC 2 Z9 2 U1 0 U2 0 PU MULTIMED INC PI TORONTO PA 66 MARTIN ST, TORONTO, ON L9T 2R2, CANADA SN 1526-9914 J9 J APPL CLIN MED PHYS JI J. Appl. Clin. Med. Phys PY 2012 VL 13 IS 3 BP 60 EP 73 PG 14 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 943QX UT WOS:000304141400006 ER PT J AU Othus, M Li, Y Tiwari, R AF Othus, Megan Li, Yi Tiwari, Ram TI Change-point cure models with application to estimating the change-point effect of age of diagnosis among prostate cancer patients SO JOURNAL OF APPLIED STATISTICS LA English DT Article DE cure models; change-point models; right censoring; smoothing; survival analysis ID LIKELIHOOD-RATIO TEST; HAZARD-RATE MODEL; SURVIVAL-DATA; COX REGRESSION; MIXTURE-MODELS; DISPARITIES; THRESHOLD; COVARIATE; OUTCOMES; RATES AB Previous research on prostate cancer survival trends in the United States National Cancer Institute's Surveillance Epidemiology and End Results database has indicated a potential change-point in the age of diagnosis of prostate cancer around age 50. Identifying a change-point value in prostate cancer survival and cure could have important policy and health care management implications. Statistical analysis of this data has to address two complicating features: (1) change-point models are not smooth functions and so present computational and theoretical difficulties; and (2) models for prostate cancer survival need to account for the fact that many men diagnosed with prostate cancer can be effectively cured of their disease with early treatment. We develop a cure survival model that allows for change-point effects in covariates to investigate a potential change-point in the age of diagnosis of prostate cancer. Our results do not indicate that age under 50 is associated with increased hazard of death from prostate cancer. C1 [Othus, Megan] Fred Hutchinson Canc Res Ctr, Seattle, WA 98117 USA. [Li, Yi] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Li, Yi] Harvard Univ, Dept Biostat, Boston, MA 02115 USA. [Tiwari, Ram] US FDA, Off Biostat, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. RP Othus, M (reprint author), Fred Hutchinson Canc Res Ctr, 1100 Fairview Ave N,M3-C102,POB 19024, Seattle, WA 98117 USA. EM mothus@fhcrc.org FU National Cancer Institute [CA090998] FX The authors thank two referees for comments that led to an improved paper. This work was supported in part by grant CA090998 from the National Cancer Institute. Most of R. Tiwari's work was done during his previous employment at the National Cancer Institute. The views expressed in this article do not necessarily represent those of the USA Food and Drug Administration or the National Cancer Institute. NR 34 TC 3 Z9 3 U1 4 U2 5 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 0266-4763 J9 J APPL STAT JI J. Appl. Stat. PY 2012 VL 39 IS 4 BP 901 EP 911 DI 10.1080/02664763.2011.626849 PG 11 WC Statistics & Probability SC Mathematics GA 947KF UT WOS:000304428200015 PM 22544992 ER PT J AU Pachas, GN Cather, C Pratt, SI Hoeppner, B Nino, J Carlini, SV Achtyes, ED Lando, H Mueser, KT Rigotti, NA Goff, DC Evins, AE AF Pachas, Gladys N. Cather, Corinne Pratt, Sarah I. Hoeppner, Bettina Nino, Johanna Carlini, Sara V. Achtyes, Eric D. Lando, Harry Mueser, Kim T. Rigotti, Nancy A. Goff, Donald C. Evins, A. Eden TI Varenicline for Smoking Cessation in Schizophrenia: Safety and Effectiveness in a 12-Week Open-Label Trial SO JOURNAL OF DUAL DIAGNOSIS LA English DT Article DE schizophrenia; smoking cessation; varenicline; CBT; open label; adverse events ID RECEPTOR PARTIAL AGONIST; RANDOMIZED CONTROLLED-TRIAL; NICOTINE REPLACEMENT THERAPY; SUSTAINED-RELEASE BUPROPION; LONGITUDINAL DATA-ANALYSIS; PLACEBO-CONTROLLED TRIAL; BIPOLAR DISORDER; DOUBLE-BLIND; CARDIOVASCULAR-DISEASE; TOBACCO DEPENDENCE AB Objective: Varenicline was approved by the FDA in 2006. In 2009, based largely on case reports, the FDA issued a warning of possible adverse neuropsychiatric effects including depression and suicidal thoughts and behavior for varenicline and bupropion. Prospective trials of varenicline have not reported increased incidence of psychiatric adverse events other than sleep disturbance, but smokers with major mental illness have been excluded from large prospective trials of varenicline to date. We sought to evaluate the effect of a standard open-label 12-week varenicline trial on prospectively assessed safety and smoking outcomes in adults with stable, treated schizophrenia spectrum disorder and nicotine dependence. Methods: One-hundred twelve stable outpatients who smoked 10 or more cigarettes/day participated in a 12-week open-label smoking cessation trial of varenicline and weekly group cognitive behavioral therapy. Participants took varenicline for 4 weeks before attempting cessation. Trained raters collected safety and smoking outcome data weekly. Results: Participants demonstrated improved psychotic symptoms, depressive symptoms, and nicotine withdrawal symptoms from baseline to week 12 or early termination. At the end of 12 weeks' open-label treatment, the 14- and 28-day continuous abstinence rates were 47.3% and 34%, respectively. Expired carbon monoxide declined significantly during treatment in those who did not achieve abstinence. Conclusions: This prospective study suggests that varenicline may be well tolerated and effective for smoking cessation in combination with group cognitive behavioral therapy in stable outpatients with schizophrenia, a group with high rates of smoking and smoking-attributable morbidity and mortality. This clinical trial is registered at www.clinicaltrials.gov as trial #NCT00621777. (Journal of Dual Diagnosis, 8: 117-125, 2012) C1 [Pachas, Gladys N.; Cather, Corinne; Hoeppner, Bettina; Nino, Johanna; Carlini, Sara V.; Rigotti, Nancy A.; Goff, Donald C.; Evins, A. Eden] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Pachas, Gladys N.; Cather, Corinne; Hoeppner, Bettina; Rigotti, Nancy A.; Goff, Donald C.; Evins, A. Eden] Harvard Univ, Sch Med, Boston, MA USA. [Pratt, Sarah I.] Geisel Sch Med Dartmouth, Concord, NH USA. [Achtyes, Eric D.] Michigan State Univ, Coll Human Med, E Lansing, MI 48824 USA. [Lando, Harry] Univ Minnesota, Div Epidemiol & Community Hlth, Minneapolis, MN USA. [Mueser, Kim T.] Boston Univ, Ctr Psychiat Rehabil, Boston, MA 02215 USA. RP Evins, AE (reprint author), MGH Ctr Addict Med, 60 Staniford St, Boston, MA 02114 USA. EM a_eden_evins@hms.harvard.edu OI Achtyes, Eric/0000-0001-8939-1535 FU NIDA NIH HHS [R01 DA021245-01A2, K24 DA030443-02, R01 DA021245-03, L30 DA025511, R01 DA021245, K24 DA030443-01, R01 DA021245-02, K24 DA030443-03, K01 DA027097, R01 DA021245-04, K24 DA030443] NR 53 TC 30 Z9 31 U1 2 U2 12 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 1550-4263 J9 J DUAL DIAGN JI J. Dual Diagn. PY 2012 VL 8 IS 2 SI SI BP 117 EP 125 DI 10.1080/15504263.2012.663675 PG 9 WC Psychology, Clinical; Substance Abuse; Psychiatry SC Psychology; Substance Abuse; Psychiatry GA 947ZW UT WOS:000304474200006 PM 22888309 ER PT J AU Lim, EJ Ober, TJ Edd, JF McKinley, GH Toner, M AF Lim, Eugene J. Ober, Thomas J. Edd, Jon F. McKinley, Gareth H. Toner, Mehmet TI Visualization of microscale particle focusing in diluted and whole blood using particle trajectory analysis SO LAB ON A CHIP LA English DT Article ID INERTIAL MIGRATION; FLOW; CELLS; VISCOSITY; TUBES; MICROCHANNELS; ERYTHROCYTES; MARGINATION; HEMATOCRIT; LEUKOCYTES AB Inertial microfluidics has demonstrated the potential to provide a rich range of capabilities to manipulate biological fluids and particles to address various challenges in biomedical science and clinical medicine. Various microchannel geometries have been used to study the inertial focusing behavior of particles suspended in simple buffer solutions or in highly diluted blood. One aspect of inertial focusing that has not been studied is how particles suspended in whole or minimally diluted blood respond to inertial forces in microchannels. The utility of imaging techniques (i.e., high-speed bright-field imaging and long exposure fluorescence (streak) imaging) primarily used to observe particle focusing in microchannels is limited in complex fluids such as whole blood due to interference from the large numbers of red blood cells (RBCs). In this study, we used particle trajectory analysis (PTA) to observe the inertial focusing behavior of polystyrene beads, white blood cells, and PC-3 prostate cancer cells in physiological saline and blood. Identification of in-focus (fluorescently labeled) particles was achieved at mean particle velocities of up to 1.85 m s(-1). Quantitative measurements of in-focus particles were used to construct intensity maps of particle frequency in the channel cross-section and scatter plots of particle centroid coordinates vs. particle diameter. PC-3 cells spiked into whole blood (HCT = 45%) demonstrated a novel focusing mode not observed in physiological saline or diluted blood. PTA can be used as an experimental frame of reference for understanding the physical basis of inertial lift forces in whole blood and discover inertial focusing modes that can be used to enable particle separation in whole blood. C1 [Lim, Eugene J.] MIT, Dept Elect Engn & Comp Sci, Cambridge, MA 02139 USA. [Lim, Eugene J.; Toner, Mehmet] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Engn Med & Surg Serv, Boston, MA 02129 USA. [Ober, Thomas J.; McKinley, Gareth H.] MIT, Dept Mech Engn, Cambridge, MA 02139 USA. [Edd, Jon F.] Vanderbilt Univ, Dept Mech Engn, Nashville, TN 37212 USA. RP Lim, EJ (reprint author), MIT, Dept Elect Engn & Comp Sci, Cambridge, MA 02139 USA. OI McKinley, Gareth/0000-0001-8323-2779 FU NIBIB NIH HHS [P41 EB002503] NR 43 TC 21 Z9 21 U1 2 U2 30 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 1473-0197 J9 LAB CHIP JI Lab Chip PY 2012 VL 12 IS 12 BP 2199 EP 2210 DI 10.1039/c2lc21100a PG 12 WC Biochemical Research Methods; Chemistry, Multidisciplinary; Nanoscience & Nanotechnology SC Biochemistry & Molecular Biology; Chemistry; Science & Technology - Other Topics GA 947RY UT WOS:000304448700013 PM 22382737 ER PT B AU Arai, K Pham, LDD Lo, EH AF Arai, Ken Pham, Loc-Duyen D. Lo, Eng H. BE Lapchak, PA Zhang, JH TI Experimental Platforms for Assessing White Matter Pathophysiology in Stroke SO TRANSLATIONAL STROKE RESEARCH: FROM TARGET SELECTION TO CLINICAL TRIALS SE Springer Series in Translational Stroke Research LA English DT Article; Book Chapter ID FOCAL CEREBRAL-ISCHEMIA; BLOOD-BRAIN-BARRIER; OLIGODENDROCYTE PROGENITOR CELLS; FREE-RADICAL SCAVENGERS; MYELIN BASIC-PROTEIN; OPTIC-NERVE ISCHEMIA; SMALL-VESSEL DISEASE; TERT-BUTYL-NITRONE; ARTERY OCCLUSION; AXONAL DAMAGE AB This chapter aims at summarizing current knowledge on experimental systems for analyzing the role of white matter injury relevant to stroke. In this chapter, we will provide a broad but brief survey of existing models at the cell, tissue, and whole-animal levels. Experimental approaches have recently allowed a better understanding of the molecular and cellular pathways underlying oligodendrocyte and oligodendrocyte precursor cell damage and demyelination. Since white matter damage is a clinically important part of stroke, a systematic utilization of these cell/tissue/whole-animal platforms related to white matter pathophysiology may eventually lead us to discover new targets for treating stroke. C1 [Arai, Ken; Pham, Loc-Duyen D.; Lo, Eng H.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neuroprotect Res Lab, Charlestown, MA 02129 USA. RP Arai, K (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neuroprotect Res Lab, Charlestown, MA 02129 USA. EM karai@partners.org; lpham1@partners.org; lo@helix.mgh.harvard.edu NR 157 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 978-1-4419-9529-2 J9 SPR SER TRANSL STROK PY 2012 BP 57 EP 78 DI 10.1007/978-1-4419-9530-8_3 D2 10.1007/978-1-4419-9530-8 PG 22 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA BAC01 UT WOS:000303777600004 ER PT B AU Hokari, M Yenari, MA AF Hokari, Masaaki Yenari, Midori A. BE Lapchak, PA Zhang, JH TI Hypothermia to Identify Therapeutic Targets for Stroke Treatment SO TRANSLATIONAL STROKE RESEARCH: FROM TARGET SELECTION TO CLINICAL TRIALS SE Springer Series in Translational Stroke Research LA English DT Article; Book Chapter ID FOCAL CEREBRAL-ISCHEMIA; TRAUMATIC BRAIN-INJURY; ANEURYSMAL SUBARACHNOID HEMORRHAGE; DELAYED POSTISCHEMIC HYPOTHERMIA; DAMAGE COOL AID; NF-KAPPA-B; MILD HYPOTHERMIA; MODERATE HYPOTHERMIA; INTRACEREBRAL HEMORRHAGE; RAT-BRAIN AB Hypothermia has emerged as a viable neuroprotectant at the clinical level. The reasons for its protective effect arc likely due to its ability to affect multiple facets of ischemic brain injury. While at times difficult to implement in humans due to various comorbidities, hypothermia can also be viewed as a tool by which neuroprotective targets may be identified. In this review, we discuss optimal conditions for therapeutic hypothermia, as evidenced by laboratory studies, as well as many of the effects of cooling on several cell death and cell survival pathways. The collective scientific literature indicates that temperature need only be decreased by a few degrees in order to confer protection, but early cooling and cooling of somewhat long duration (12-24 h) seem to be the more critical factors that determine success. Hypothermia seems to halt many damaging processes that lead to brain tissue injury, while upregulating factors that aid in its recovery. However, it should be noted that not all forms of brain injury benefit front therapeutic cooling. While global and focal cerebral ischemia appears to benefit from hypothermia, it is less clear whether brain hemorrhage responds in the same way. Thus, the laboratory literature also emphasizes the importance of careful preclinical studies prior to applying such concepts to humans. C1 [Hokari, Masaaki; Yenari, Midori A.] Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94121 USA. [Hokari, Masaaki; Yenari, Midori A.] San Francisco VA Med Ctr, San Francisco, CA 94121 USA. RP Yenari, MA (reprint author), Univ Calif San Francisco, Dept Neurol, 4150 Clement St, San Francisco, CA 94121 USA. EM karimasa@med.hokudai.ac.jp; Yenari@alum.mit.edu NR 100 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 978-1-4419-9529-2 J9 SPR SER TRANSL STROK PY 2012 BP 305 EP 320 DI 10.1007/978-1-4419-9530-8_15 D2 10.1007/978-1-4419-9530-8 PG 16 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA BAC01 UT WOS:000303777600016 ER PT B AU Yu, ZY Liu, N Wang, XY AF Yu, Zhanyang Liu, Ning Wang, Xiaoying BE Lapchak, PA Zhang, JH TI Neuroglobin: A Novel Target for Endogenous Neuroprotection SO TRANSLATIONAL STROKE RESEARCH: FROM TARGET SELECTION TO CLINICAL TRIALS SE Springer Series in Translational Stroke Research LA English DT Article; Book Chapter ID NUCLEOTIDE DISSOCIATION INHIBITOR; OUTER MITOCHONDRIAL-MEMBRANE; CYTOCHROME BC(1) COMPLEX; FOCAL CEREBRAL-ISCHEMIA; NEURON GENE SMN; SMALL-MOLECULE; NITRIC-OXIDE; GLUCOSE DEPRIVATION; OXIDATIVE STRESS; SH-SY5Y CELLS AB Augmentation of endogenous protective mechanisms has been thought to he promising strategies to develop new therapies against stroke. Neuroglobin (Ngb) is a tissue oxygen-binding globin that is highly and specifically expressed in brain neurons. Accumulating evidences have proved Ngb is a unique endogenous neuroprotective molecule against hypoxic/ischemic insults in cultured neurons and in stroke animals, which strongly suggest that development of pharmacological strategies that upregulate endogenous Ngb expression may lead to a novel therapeutic approach for stroke intervention. In this chapter, recent experimental findings from our laboratory and others in understanding Ngb's biological function, gene expression regulation, and neuroprotective mechanisms are summarized. We also propose strategies to identify small molecules that upregulate endogenous Ngb for neuroprotection against stroke and related neurological disorders. Briefly, the strategies comprise two translational features. First, we will establish both mouse and human Ngb gene activation reporter stable cell lines to ensure that only compounds capable of activating both mouse and human Ngb promoters will be selected for further testing. Second, validation is the key component of any single step in drug screening and therapeutic development processes. C1 [Yu, Zhanyang; Liu, Ning; Wang, Xiaoying] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neuroprotect Res Lab,Dept Neurol, Charlestown, MA 02129 USA. [Yu, Zhanyang; Liu, Ning; Wang, Xiaoying] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neuroprotect Res Lab,Dept Radiol, Charlestown, MA 02129 USA. RP Wang, XY (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neuroprotect Res Lab,Dept Neurol, 149 13th St,Room 2411A, Charlestown, MA 02129 USA. EM zyu@partners.org; liuning0731@yahoo.cn; wangxi@helix.mgh.harvard.edu NR 107 TC 0 Z9 0 U1 0 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 978-1-4419-9529-2 J9 SPR SER TRANSL STROK PY 2012 BP 353 EP 372 DI 10.1007/978-1-4419-9530-8_18 D2 10.1007/978-1-4419-9530-8 PG 20 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA BAC01 UT WOS:000303777600019 ER PT J AU Maneta, E Cohen, S Schulz, M Waldinger, RJ AF Maneta, Eleni Cohen, Shiri Schulz, Marc Waldinger, Robert J. TI Links Between Childhood Physical Abuse and Intimate Partner Aggression: The Mediating Role of Anger Expression SO VIOLENCE AND VICTIMS LA English DT Article DE childhood abuse; revictimization; intimate partner violence; couples ID POSTTRAUMATIC-STRESS-DISORDER; CONFLICT-TACTICS-SCALES; ADULT VICTIMIZATION; SEXUAL-ABUSE; RISK-FACTORS; VIOLENCE; PERPETRATION; DISSOCIATION; EXPERIENCES; RECOMMENDATIONS AB Research linking childhood physical abuse (CPA) and adult intimate partner aggression (IPA) has focused on individuals without sufficient attention to couple processes. In this study, 109 couples reported on histories of CPA, IPA, and anger expression. Actor-partner interdependence model (APIM) was used to examine links between CPA and revictimization and perpetration of IPA, with anger suppression as a potential mediator. Women's CPA histories were associated with more physical aggression towards and more revictimization by partners. Men's CPA histories were only associated at the trend level with their revictimization. Anger suppression fully mediated the link between women's CPA and both revictimization and perpetration of IPA. Findings suggest that women with CPA histories are more prone to suppress anger, which leaves them at greater risk for revictimization and perpetration of IPA. C1 [Maneta, Eleni] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02114 USA. [Cohen, Shiri; Waldinger, Robert J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Schulz, Marc] Bryn Mawr Coll, Bryn Mawr, PA 19010 USA. RP Maneta, E (reprint author), Harvard Univ, Sch Med, Dept Psychiat, 151 Merrimac St,2nd Floor, Boston, MA 02114 USA. EM manetael@gmail.com FU NIMH NIH HHS [K08MH01555] NR 44 TC 14 Z9 14 U1 4 U2 20 PU SPRINGER PUBLISHING CO PI NEW YORK PA 11 WEST 42ND STREET, NEW YORK, NY 10036 USA SN 0886-6708 J9 VIOLENCE VICTIMS JI Violence Vict. PY 2012 VL 27 IS 3 BP 315 EP 328 DI 10.1891/0886-6708.27.3.315 PG 14 WC Criminology & Penology SC Criminology & Penology GA 949VD UT WOS:000304603200002 PM 22852434 ER PT J AU Hendricks, JA Keliher, EJ Wan, DP Hilderbrand, SA Weissleder, R Mazitschek, R AF Hendricks, J. Adam Keliher, Edmund J. Wan, Dongpeng Hilderbrand, Scott A. Weissleder, Ralph Mazitschek, Ralph TI Synthesis of [F-18]BODIPY: Bifunctional Reporter for Hybrid Optical/Positron Emission Tomography Imaging SO ANGEWANDTE CHEMIE-INTERNATIONAL EDITION LA English DT Article DE dyes/pigments; fluorescent probes; imaging agents; radiopharmaceuticals; synthetic methods ID CANCER; PROBES; PET C1 [Hendricks, J. Adam; Keliher, Edmund J.; Wan, Dongpeng; Hilderbrand, Scott A.; Weissleder, Ralph; Mazitschek, Ralph] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Syst Biol, Boston, MA 02114 USA. RP Weissleder, R (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Syst Biol, Boston, MA 02114 USA. EM rweissleder@mgh.harvard.edu; rmazitschek@mgh.harvard.edu RI Mazitschek, Ralph/E-3741-2013 OI Mazitschek, Ralph/0000-0002-1105-689X FU NCI [P50A086355, U24A092782, T32-CA079443] FX Financial support from the NCI (P50A086355, U24A092782, T32-CA079443) is gratefully acknowledged. NR 14 TC 54 Z9 54 U1 3 U2 37 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA BOSCHSTRASSE 12, D-69469 WEINHEIM, GERMANY SN 1433-7851 J9 ANGEW CHEM INT EDIT JI Angew. Chem.-Int. Edit. PY 2012 VL 51 IS 19 BP 4603 EP 4606 DI 10.1002/anie.201107957 PG 4 WC Chemistry, Multidisciplinary SC Chemistry GA 935GJ UT WOS:000303506800016 PM 22473535 ER PT S AU Whitfield-Gabrieli, S Ford, JM AF Whitfield-Gabrieli, Susan Ford, Judith M. BE NolenHoeksema, S TI Default Mode Network Activity and Connectivity in Psychopathology SO ANNUAL REVIEW OF CLINICAL PSYCHOLOGY, VOL 8 SE Annual Review of Clinical Psychology LA English DT Article; Book Chapter DE resting state; schizophrenia; depression ID RESTING HUMAN BRAIN; STATE FUNCTIONAL CONNECTIVITY; MEDIAL PREFRONTAL CORTEX; TREATMENT-RESISTANT DEPRESSION; POSITRON-EMISSION-TOMOGRAPHY; FREQUENCY BOLD FLUCTUATIONS; ANTERIOR CINGULATE CORTEX; MAJOR DEPRESSION; BIPOLAR DISORDER; WORKING-MEMORY AB Neuropsychiatric disorders are associated with abnormal function of the default mode network (DMN), a distributed network of brain regions more active during rest than during performance of many attention-demanding tasks and characterized by a high degree of functional connectivity (i.e., temporal correlations between brain regions). Functional magnetic resonance imaging studies have revealed that the DMN in the healthy brain is associated with stimulus-independent thought and self-reflection and that greater suppression of the DMN is associated with better performance on attention-demanding tasks. In schizophrenia and depression, the DMN is often found to be hyperactivated and hyperconnected. In schizophrenia this may relate to overly intensive self-reference and impairments in attention and working memory. In depression, DMN hyperactivity may be related to negative rumination. These findings are considered in terms of what is known about psychological functions supported by the DMN, and alteration of the DMN in other neuropsychiatric disorders. C1 [Whitfield-Gabrieli, Susan] MIT, Dept Brain & Cognit Sci, Cambridge, MA 02139 USA. [Ford, Judith M.] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94121 USA. [Ford, Judith M.] Univ Calif San Francisco, San Francisco Vet Adm Med Ctr, San Francisco, CA 94121 USA. RP Whitfield-Gabrieli, S (reprint author), MIT, Dept Brain & Cognit Sci, E25-618, Cambridge, MA 02139 USA. EM swg@mit.edu NR 188 TC 320 Z9 331 U1 17 U2 111 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0897 USA SN 1548-5943 BN 978-0-8243-3908-1 J9 ANNU REV CLIN PSYCHO JI Annu. Rev. Clin. Psychol. PY 2012 VL 8 BP 49 EP + DI 10.1146/annurev-clinpsy-032511-143049 PG 37 WC Psychology, Clinical; Psychology SC Psychology GA BAH99 UT WOS:000304200200004 PM 22224834 ER PT S AU Pillai, S Netravali, IA Cariappa, A Mattoo, H AF Pillai, Shiv Netravali, Ilka Arun Cariappa, Annaiah Mattoo, Hamid BE Paul, WE TI Siglecs and Immune Regulation SO ANNUAL REVIEW OF IMMUNOLOGY, VOL 30 SE Annual Review of Immunology LA English DT Review; Book Chapter DE inhibitory receptors; tolerance; autoimmunity; inflammation; clonal ignorance ID PLASMACYTOID DENDRITIC CELLS; ACID-BINDING-RECEPTOR; NATURAL-KILLER-CELLS; LYN-DEFICIENT MICE; MYELIN-ASSOCIATED GLYCOPROTEIN; PROTEIN-TYROSINE PHOSPHATASES; ALPHA-2,6-LINKED SIALIC ACIDS; LYMPHOCYTE ADHESION MOLECULE; HUMAN-EOSINOPHIL APOPTOSIS; I-TYPE LECTINS AB Sialic acid-binding Ig-like lectins, or Siglecs, vary in their specificity for sialic acid-containing ligands and are mainly expressed by cells of the immune system. Many Siglecs are inhibitory receptors expressed in innate immune cells that regulate inflammation mediated by damage-associated and pathogen-associated molecular patterns (DAMPs and PAMPs). This family also includes molecules involved in adhesion and phagocytosis and receptors that can associate with the ITAM-containing DAP12 adaptor. Siglecs contribute to the inhibition of immune cells both by binding to cis ligands (expressed in the same cells) and by responding to pathogen-derived sialoglycoconjugates. They can help maintain tolerance in B lymphocytes, modulate the activation of conventional and plasmacytoid dendritic cells, and contribute to the regulation of T cell function both directly and indirectly. Siglecs modulate immune responses, influencing almost every cell in the immune system, and are of relevance both in health and disease. C1 [Pillai, Shiv; Netravali, Ilka Arun; Cariappa, Annaiah; Mattoo, Hamid] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Canc Res, Boston, MA 02129 USA. RP Pillai, S (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Canc Res, Boston, MA 02129 USA. EM pillai@helix.mgh.harvard.edu; ilka_netravali@hms.harvard.edu; cariappa@helix.mgh.harvard.edu; hmattoo@partners.org FU NIAID NIH HHS [AI064930, AI076505, AI090867, R01 AI064930, R01 AI076505, R01 AI090867]; NIAMS NIH HHS [AR058481, RC1 AR058481]; NIDDK NIH HHS [P30 DK043351] NR 169 TC 103 Z9 106 U1 3 U2 36 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0897 USA SN 0732-0582 BN 978-0-8243-3030-9 J9 ANNU REV IMMUNOL JI Annu. Rev. Immunol. PY 2012 VL 30 BP 357 EP 392 DI 10.1146/annurev-immunol-020711-075018 PG 36 WC Immunology SC Immunology GA BAH94 UT WOS:000304198100016 PM 22224769 ER PT S AU Kuballa, P Nolte, WM Castoreno, AB Xavier, RJ AF Kuballa, Petric Nolte, Whitney M. Castoreno, Adam B. Xavier, Ramnik J. BE Paul, WE TI Autophagy and the Immune System SO ANNUAL REVIEW OF IMMUNOLOGY, VOL 30 SE Annual Review of Immunology LA English DT Review; Book Chapter DE macroautophagy; virus; bacterial infection; innate immunity; adaptive immunity; xenophagy ID ACTIVATED PROTEIN-KINASE; REGULATES AGGRESOME FORMATION; STARVATION-INDUCED AUTOPHAGY; STRESS-INDUCED AUTOPHAGY; NF-KAPPA-B; PHOSPHATIDYLINOSITOL 3-KINASE COMPLEXES; CHAPERONE-MEDIATED AUTOPHAGY; TRANSCRIPTION FACTOR NRF2; GENOME-WIDE ASSOCIATION; PROGRAMMED CELL-DEATH AB Stressors ranging from nutrient deprivation to immune signaling can induce the degradation of cytoplasmic material by a process known as autophagy. Increasingly, research on autophagy has begun to focus on its role in inflammation and the immune response. Autophagy acts as an immune effector that mediates pathogen clearance. The roles of autophagy bridge both the innate and adaptive immune systems and include functions in thymic selection, antigen presentation, promotion of lymphocyte homeostasis and survival, and regulation of cytokine production. In this review, we discuss the mechanisms by which autophagy is regulated, as well as the functions of autophagy and autophagy proteins in immunity and inflammation. C1 [Kuballa, Petric; Nolte, Whitney M.; Castoreno, Adam B.; Xavier, Ramnik J.] MIT, Broad Inst, Cambridge, MA 02142 USA. [Kuballa, Petric; Nolte, Whitney M.; Castoreno, Adam B.; Xavier, Ramnik J.] Univ Cambridge, Cambridge, MA 02142 USA. [Kuballa, Petric; Nolte, Whitney M.; Castoreno, Adam B.; Xavier, Ramnik J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Computat & Integrat Biol, Boston, MA 02114 USA. [Xavier, Ramnik J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastrointestinal Unit, Boston, MA 02114 USA. [Xavier, Ramnik J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Study Inflammatory Bowel Dis, Boston, MA 02114 USA. RP Kuballa, P (reprint author), MIT, Broad Inst, Cambridge, MA 02142 USA. EM pkuballa@ccib.mgh.harvard.edu; whitney@broadinstitute.org; acastore@broadinstitute.org; xavier@molbio.mgh.harvard.edu FU NIDDK NIH HHS [P30DK043351, 5R01DK064869, 5R01DK083756, 5U01DK062432, P30 DK043351, R01 DK064869, R01 DK083756, RC1 DK086502, RC1DK086502] NR 328 TC 125 Z9 138 U1 7 U2 49 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0897 USA SN 0732-0582 BN 978-0-8243-3030-9 J9 ANNU REV IMMUNOL JI Annu. Rev. Immunol. PY 2012 VL 30 BP 611 EP + DI 10.1146/annurev-immunol-020711-074948 PG 50 WC Immunology SC Immunology GA BAH94 UT WOS:000304198100023 PM 22449030 ER PT J AU Halpin, C Rauch, SD AF Halpin, Chris Rauch, Steven D. TI Improvement in Word Recognition Score with Level Is Associated with Hearing Aid Ownership among Patients with Hearing Loss SO AUDIOLOGY AND NEURO-OTOLOGY LA English DT Article DE Hearing aid, recommendation; Hearing loss; Speech Intelligibility Index AB Market surveys consistently show that only 22% of those with hearing loss own hearing aids. This is often ascribed to cosmetics, but is it possible that patients apply a different auditory criterion than do audiologists and manufacturers? We tabulated hearing aid ownership in a survey of 1000 consecutive patients. We separated hearing loss cases, with one cohort in which word recognition in quiet could improve with gain (vs. 40 dB HL) and another without such improvement but nonetheless with audiometric thresholds within the manufacturer's fitting ranges. Overall, we found that exactly 22% of hearing loss patients in this sample owned hearing aids; the same finding has been reported in many previous, well-accepted surveys. However, while all patients in the two cohorts experienced difficulty in noise, patients in the cohort without word recognition improvement were found to own hearing aids at a rate of 0.3%, while those patients whose word recognition could increase with level were found to own hearing aids at a rate of 50%. Results also coherently fit a logistic model where shift of the word recognition performance curve by level corresponded to the likelihood of ownership. In addition to the common attribution of low hearing aid usage to patient denial, cosmetic issues, price, or social stigma, these results provide one alternative explanation based on measurable improvement in word recognition performance. Copyright (C) 2011 S. Karger AG, Basel C1 [Halpin, Chris] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Audiol, Boston, MA 02114 USA. [Rauch, Steven D.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Otolaryngol, Boston, MA 02114 USA. [Halpin, Chris; Rauch, Steven D.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02114 USA. RP Halpin, C (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Audiol, 243 Charles St, Boston, MA 02114 USA. EM chris_halpin@meei.harvard.edu NR 11 TC 1 Z9 1 U1 0 U2 4 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1420-3030 J9 AUDIOL NEURO-OTOL JI Audiol. Neuro-Otol. PY 2012 VL 17 IS 3 BP 139 EP 147 DI 10.1159/000333777 PG 9 WC Audiology & Speech-Language Pathology; Neurosciences; Otorhinolaryngology SC Audiology & Speech-Language Pathology; Neurosciences & Neurology; Otorhinolaryngology GA 948CL UT WOS:000304481100001 PM 22104328 ER PT J AU de Heer, AMR Merchant, SN Kammeraad, JAE Cruysberg, JRM Huygen, PLM Cremers, CWRJ AF de Heer, Anne-Martine R. Merchant, Saumil N. Kammeraad, Janneke A. E. Cruysberg, Johannes R. M. Huygen, Patrick L. M. Cremers, Cor W. R. J. TI Clinical Follow-Up and Histopathology of the Temporal Bones in Nathalie Syndrome SO AUDIOLOGY AND NEURO-OTOLOGY LA English DT Article DE Genetic hearing impairment; Nathalie syndrome; Juvenile cataract; Cardiomyopathy; Heart failure ID SENSORINEURAL HEARING-LOSS; SNELLS-WALTZER MICE; HYPERTROPHIC CARDIOMYOPATHY; DILATED CARDIOMYOPATHY; HUMAN HOMOLOG; HAIR-CELLS; MYOSIN-VI; DEAFNESS; MUTATION; EYA4 AB The Nathalie syndrome (OMIM 255990) comprises a combination of features that do not resemble any other known syndrome and is as such an independent, rare entity. It is characterized by sensorineural hearing impairment, juvenile cataract, spinal muscular atrophy, skeletal abnormalities, retardation of growth, underdeveloped secondary gender characteristics and cardiomyopathy. Worldwide, only one family with this syndrome is known. An update of the clinical follow-up in this family and the results of autopsy are given. Audiometry showed a downsloping configuration that corresponded to the findings at histopathological examination of the cochlea: a diffuse atrophy of the organ of Corti, severe and diffuse atrophy of the stria vascularis and moderate loss of cochlear neurons in all turns. Another new striking feature is that individuals with the Nathalie syndrome have a shortened life expectancy with a risk of sudden death or death from heart failure resulting from (dilated) cardiomyopathy. Copyright (C) 2012 S. Karger AG, Basel C1 [de Heer, Anne-Martine R.; Huygen, Patrick L. M.] Radboud Univ Nijmegen, Med Ctr, Dept Otorhinolaryngol, NL-6500 HB Nijmegen, Netherlands. [Kammeraad, Janneke A. E.] Radboud Univ Nijmegen, Med Ctr, Dept Cardiol, NL-6500 HB Nijmegen, Netherlands. [Cruysberg, Johannes R. M.] Radboud Univ Nijmegen, Med Ctr, Dept Ophthalmol, NL-6500 HB Nijmegen, Netherlands. [de Heer, Anne-Martine R.; Huygen, Patrick L. M.] Radboud Univ Nijmegen, Donders Inst Brain Cognit & Behav, NL-6500 HB Nijmegen, Netherlands. [Merchant, Saumil N.; Cremers, Cor W. R. J.] Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Otopathol Lab, Boston, MA 02114 USA. [Merchant, Saumil N.; Cremers, Cor W. R. J.] Harvard Univ, Sch Med, Boston, MA USA. RP de Heer, AMR (reprint author), Radboud Univ Nijmegen, Med Ctr, Dept Otorhinolaryngol, POB 9101, NL-6500 HB Nijmegen, Netherlands. EM A.deHeer@kno.umcn.nl RI Cruysberg, Johannes/D-4313-2009; Cremers, C.W.R.J./L-4254-2015; Huygen, P.L.M./L-4401-2015 OI Cruysberg, Johannes/0000-0002-5330-0774; FU Heinsius Houbolt Foundation; European Commission; NIH [U24DC008559]; [LSHG-CT-20054-512063] FX This work was supported by the Heinsius Houbolt Foundation, the European Commission FP6 Integrated Project EUROHEAR, both assigned to C.W.R.J. Cremers, LSHG-CT-20054-512063, NIH grant U24DC008559, Mr. Lakshmi Mittal and Mr. Axel Eliasen. NR 20 TC 1 Z9 1 U1 0 U2 2 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1420-3030 J9 AUDIOL NEURO-OTOL JI Audiol. Neuro-Otol. PY 2012 VL 17 IS 4 BP 219 EP 227 DI 10.1159/000336212 PG 9 WC Audiology & Speech-Language Pathology; Neurosciences; Otorhinolaryngology SC Audiology & Speech-Language Pathology; Neurosciences & Neurology; Otorhinolaryngology GA 948CY UT WOS:000304482400002 PM 22487897 ER PT J AU Bramoweth, AD Taylor, DJ AF Bramoweth, Adam D. Taylor, Daniel J. TI Chronic Insomnia and Health Care Utilization in Young Adults SO BEHAVIORAL SLEEP MEDICINE LA English DT Article ID EPWORTH SLEEPINESS SCALE; QUALITY-OF-LIFE; PSYCHIATRIC-DISORDERS; GENERAL-POPULATION; ECONOMIC BURDEN; INDIRECT COSTS; UNITED-STATES; DEPRESSION; INVENTORY; EPIDEMIOLOGY AB Chronic insomnia is prevalent, contributes a significant economic burden, and people with insomnia have increased health care utilization (HCU). The purpose of this study was to investigate the relationship between chronic insomnia and HCU in a population with fewer medical/mental health problems, using current operational definitions of chronic insomnia and multiple measures of HCU. Participants with chronic insomnia had greater HCU than normal sleepers. Participants with chronic insomnia plus a comorbid condition had greater HCU than normal sleepers with a medical/mental health problem and participants with only chronic insomnia. The relationship between chronic insomnia and HCU was moderated by comorbid medical/mental health problems. Early identification and intervention of chronic insomnia may help reduce HCU and costs associated with chronic insomnia. C1 [Bramoweth, Adam D.] Pittsburgh Healthcare Syst, VISN Mental Illness Res Educ & Clin Ctr MIRECC 4, Pittsburgh, PA USA. [Taylor, Daniel J.] Univ N Texas, Dept Psychol, Ft Worth, TX USA. RP Bramoweth, AD (reprint author), VA Pittsburgh Healthcare Syst, 7180 Highland Dr,151R-H, Pittsburgh, PA 15206 USA. EM adam.bramoweth@va.gov OI Bramoweth, Adam/0000-0002-3535-0292 NR 55 TC 9 Z9 9 U1 1 U2 4 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 1540-2002 J9 BEHAV SLEEP MED JI Behav. Sleep Med. PY 2012 VL 10 IS 2 BP 106 EP 121 DI 10.1080/15402002.2011.587067 PG 16 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 945ME UT WOS:000304277100003 PM 22468929 ER PT J AU Wisco, BE Treat, TA Hollingworth, A AF Wisco, Blair E. Treat, Teresa A. Hollingworth, Andrew TI Visual attention to emotion in depression: Facilitation and withdrawal processes SO COGNITION & EMOTION LA English DT Article DE Depression; Visual attention; Attentional bias; Cognitive bias ID SELECTIVE ATTENTION; FACIAL EXPRESSIONS; NEGATIVE INFORMATION; UNIPOLAR DEPRESSION; SOCIAL PHOBIA; BIASES; DYSPHORIA; ANXIETY; DISENGAGEMENT; MOOD AB Attentional biases for sadness are integral to cognitive theories of depression, but do not emerge under all conditions. Some researchers have argued that depression is associated with delayed withdrawal from, but not facilitated initial allocation of attention toward, sadness. We compared two types of withdrawal processes in clinically depressed and non-depressed individuals: (1) withdrawal requiring overt eye movements during visual search; and (2) covert disengagement of attention in a modified cueing paradigm. We also examined initial allocation of attention towards emotion on the visual search task, allowing comparison of withdrawal and facilitation processes. As predicted, we found no evidence of facilitated attention towards sadness in depressed individuals. However, we also found no evidence of depression-linked differences in withdrawal of attention from sadness on either task, offering no support for the theory that depression is associated with withdrawal rather than initial facilitation of attention. C1 [Wisco, Blair E.] Yale Univ, Dept Psychol, New Haven, CT 06520 USA. [Treat, Teresa A.; Hollingworth, Andrew] Univ Iowa, Dept Psychol, Iowa City, IA 52242 USA. RP Wisco, BE (reprint author), VA Boston Healthcare Syst, 150 S Huntington Ave,116B, Boston, MA 02130 USA. EM Blair.wisco@va.gov FU NEI NIH HHS [R01 EY017356] NR 42 TC 5 Z9 5 U1 6 U2 29 PU PSYCHOLOGY PRESS PI HOVE PA 27 CHURCH RD, HOVE BN3 2FA, EAST SUSSEX, ENGLAND SN 0269-9931 J9 COGNITION EMOTION JI Cogn. Emot. PY 2012 VL 26 IS 4 BP 602 EP 614 DI 10.1080/02699931.2011.595392 PG 13 WC Psychology, Experimental SC Psychology GA 945YC UT WOS:000304311800003 PM 21851151 ER PT J AU Stewart, SE Hezel, D Stachon, AC AF Stewart, S. Evelyn Hezel, Dianne Stachon, Andrea C. TI Assessment and Medication Management of Paediatric Obsessive-Compulsive Disorder SO DRUGS LA English DT Article ID RANDOMIZED CONTROLLED-TRIAL; PLACEBO-CONTROLLED TRIAL; COGNITIVE-BEHAVIOR THERAPY; LONG-TERM TREATMENT; INTENSIVE RESIDENTIAL-TREATMENT; INVENTORY-CHILD VERSION; DOUBLE-BLIND; EARLY-ONSET; D-CYCLOSERINE; PSYCHOMETRIC PROPERTIES AB Paediatric obsessive-compulsive disorder (OCD) is a common, yet under recognized, neuropsychiatric illness in both clinical and community settings. Symptoms tend to be hidden or misunderstood by affected youth, and parents may inadvertently accommodate OCD, thus worsening its severity. These symptoms may include compulsive reassurance seeking, confessing and 'just right' rituals, in addition to more classic OCD behaviours. Fortunately, numerous psychometric measures are available to assist in clinical assessment of this disorder and its sequelae. Once properly diagnosed, paediatric OCD is highly treatable with empirically proven approaches including cognitive-behaviour therapy (CBT) and serotonin reuptake inhibitor (SRI) medications. Clinically meaningful symptom improvement is the norm following these strategies, although full remission is not, as symptoms tend to wax and wane over time. Paediatric OCD is highly co-morbid with other anxiety disorders, tic disorders, depression and attention-deficit hyperactivity disorder, which also require specific attention. For moderate to severe OCD, an interdisciplinary approach combining individual and family CBT with SRI trials is recommended. For severe treatment-refractory illness, early evidence supports the benefit of augmenting agents, such as atypical antipsychotics and potentially those with glutamatergic activity. Clinical outcome assessment in paediatric OCD should always include broad domains of individual and family functioning, in addition to symptom improvement. C1 [Stachon, Andrea C.] Univ British Columbia, Dept Psychiat, OCD Program, BC Childrens Hosp, Vancouver, BC V5Z 4H4, Canada. [Stewart, S. Evelyn] McLean Hosp, Belmont, MA 02178 USA. [Stewart, S. Evelyn; Hezel, Dianne] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Stewart, S. Evelyn] Harvard Univ, Sch Med, Boston, MA USA. RP Stewart, SE (reprint author), Univ British Columbia, Dept Psychiat, OCD Program, BC Childrens Hosp, A3-118,W 28th Ave, Vancouver, BC V5Z 4H4, Canada. EM evelyn.stewart@ubc.ca OI Stewart, S. Evelyn/0000-0002-0994-6383 FU Toronto Hospital for Sick Children Research Institute; Michael Smith Foundation for Health Research (MSFHR); American Academy of Child and Adolescent Psychiatry (AACAP); University of British Columbia (UBC); British Columbia Mental Health and Addictions Research Institute (BCMHARI) FX The authors would like to acknowledge the invaluable assistance of Rhonda Ellwyn and Annie Kuan in manuscript preparation and formatting. In addition, Dr Stachon received funding from a Toronto Hospital for Sick Children Research Institute Clinician-Scientist Training Program Scholarship. Dr Stewart received funding from several sources that were used to support the article preparation: the Michael Smith Foundation for Health Research (MSFHR), American Academy of Child and Adolescent Psychiatry (AACAP), University of British Columbia (UBC) and British Columbia Mental Health and Addictions Research Institute (BCMHARI). None of the authors have conflicts of interest to report. NR 106 TC 4 Z9 4 U1 3 U2 18 PU ADIS INT LTD PI AUCKLAND PA 41 CENTORIAN DR, PRIVATE BAG 65901, MAIRANGI BAY, AUCKLAND 1311, NEW ZEALAND SN 0012-6667 J9 DRUGS JI Drugs PY 2012 VL 72 IS 7 BP 881 EP 893 PG 13 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 945RM UT WOS:000304293700002 PM 22564131 ER PT J AU Largent, EA Pearson, SD AF Largent, Emily A. Pearson, Steven D. TI Which ORPHANS Will Find a HOME? The Rule of Rescue in Resource Allocation for Rare Diseases SO HASTINGS CENTER REPORT LA English DT Article ID CELL LUNG-CANCER; DRUGS; PRIORITY; THERAPY; COST; CARE C1 [Largent, Emily A.] NIH, Dept Bioeth, Bethesda, MD 20892 USA. [Pearson, Steven D.] Massachusetts Gen Hosp, Inst Clin & Econ Review, Boston, MA 02114 USA. RP Largent, EA (reprint author), Harvard Univ, PhD Program Hlth Policy, Cambridge, MA 02138 USA. NR 30 TC 14 Z9 14 U1 1 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0093-0334 J9 HASTINGS CENT REP JI Hastings Cent. Rep. PD JAN-FEB PY 2012 VL 42 IS 1 BP 27 EP 34 DI 10.1002/HAST.12 PG 8 WC Ethics; Health Care Sciences & Services; Medical Ethics; Social Sciences, Biomedical SC Social Sciences - Other Topics; Health Care Sciences & Services; Medical Ethics; Biomedical Social Sciences GA 946YU UT WOS:000304394500017 PM 22616398 ER PT J AU Lewis, N Martinez, LS Freres, DR Schwartz, JS Armstrong, K Gray, SW Fraze, T Nagler, RH Bourgoin, A Hornik, RC AF Lewis, Nehama Martinez, Lourdes S. Freres, Derek R. Schwartz, J. Sanford Armstrong, Katrina Gray, Stacy W. Fraze, Taressa Nagler, Rebekah H. Bourgoin, Angel Hornik, Robert C. TI Seeking Cancer-Related Information From Media and Family/Friends Increases Fruit and Vegetable Consumption Among Cancer Patients SO HEALTH COMMUNICATION LA English DT Article ID COLORECTAL ADENOMAS; PROSTATE-CANCER; RISK; BEHAVIOR; METAANALYSIS; PREVENTION; PATTERNS; THERAPY; HEALTH AB Previous research suggests positive effects of health information seeking on prevention behaviors such as diet, exercise, and fruit and vegetable consumption among the general population. The current study builds upon this research by examining the effect of cancer patients' active information seeking from media and (nonmedical) interpersonal sources on fruit and vegetable consumption. The results of this longitudinal study are based on data collected from a randomly drawn sample from the Pennsylvania Cancer Registry, comprising breast, prostate, and colorectal cancer patients who completed mail surveys in the fall of 2006 and 2007. There was a 65% response rate for baseline subjects (resulting n = 2013); of those, 1,293 were interviewed one year later and 845 were available for final analyses. We used multiple imputation to replace missing data and propensity scoring to adjust for effects of possible confounders. There is a positive effect of information seeking at baseline on fruit and vegetable servings at follow-up; seekers consumed 0.43 (95% CI: 0.28 to 0.58) daily servings more than nonseekers adjusting for baseline consumption and other confounders. Active information seeking from media and interpersonal sources may lead to improved nutrition among the cancer patient population. C1 [Lewis, Nehama] Florida Int Univ, Dept Psychol, Community Based Intervent Res Grp, Miami, FL 33199 USA. [Martinez, Lourdes S.; Freres, Derek R.; Bourgoin, Angel; Hornik, Robert C.] Univ Penn, Annenberg Sch Commun, Philadelphia, PA 19104 USA. [Schwartz, J. Sanford; Armstrong, Katrina] Univ Penn, Dept Med, Philadelphia, PA 19104 USA. [Schwartz, J. Sanford] Univ Penn, Wharton Sch, Philadelphia, PA 19104 USA. [Gray, Stacy W.] Harvard Univ, Dana Farber Canc Inst, Cambridge, MA 02138 USA. [Fraze, Taressa] Thomson Reuters, Healthcare Div, Santa Barbara, CA USA. [Nagler, Rebekah H.] Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst, Cambridge, MA 02138 USA. RP Lewis, N (reprint author), Florida Int Univ, Dept Psychol, Community Based Intervent Res Grp, MARC 310,11200 SW 8th St, Miami, FL 33199 USA. EM nehamalewis@gmail.com OI Hornik, Robert/0000-0002-2148-8805 FU NCI NIH HHS [P20 CA095856, P50 CA095856, P50-CA095856-05] NR 39 TC 21 Z9 21 U1 3 U2 10 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 1041-0236 EI 1532-7027 J9 HEALTH COMMUN JI Health Commun. PY 2012 VL 27 IS 4 BP 380 EP 388 DI 10.1080/10410236.2011.586990 PG 9 WC Communication; Health Policy & Services SC Communication; Health Care Sciences & Services GA 946BO UT WOS:000304323800006 PM 21932985 ER PT J AU Ravona-Springer, R Moshier, E Schmeidler, J Godbold, J Akrivos, J Rapp, M Grossman, HT Wysocki, M Silverman, JM Haroutunian, V Beeri, MS AF Ravona-Springer, Ramit Moshier, Erin Schmeidler, James Godbold, James Akrivos, Jimmy Rapp, Michael Grossman, Hillel T. Wysocki, Michael Silverman, Jeremy M. Haroutunian, Vahram Beeri, Michal Schnaider TI Changes in Glycemic Control are Associated with Changes in Cognition in Non-Diabetic Elderly SO JOURNAL OF ALZHEIMERS DISEASE LA English DT Article DE Cognition; elderly; glucose control; HbA1c; non-diabetic ID MINI-MENTAL-STATE; ALZHEIMER-DISEASE; OLDER-ADULTS; GLYCATED HEMOGLOBIN; DIABETES-MELLITUS; ALL-CAUSE; DEMENTIA; IMPAIRMENT; BRAIN; POPULATION AB The aim of the present study was to examine the relationship of changes in long term glucose levels as measured by Hemoglobin A1c (HbA1c) with simultaneous changes in cognition. The sample included in the present analysis consisted of 101 community dwelling non-diabetic elderly subjects participating in ongoing longitudinal studies of cognition. Subjects were included in this study if they were cognitively normal at baseline, had at least one co-temporaneous follow-up assessment of HbA1c and the Mini Mental State Exam (MMSE), and complete data on age, gender, race, and years of education. MMSE decline over time was the main outcome measure. In TOBIT mixed regression models, MMSE was the dependent variable and HbA1c the time-varying covariate. Sociodemographic (age, gender, and education), cardiovascular (hypertension and APOE4 status), and lifestyle (smoking and physical activity) covariates were included in the statistical model. After adjusting for age at follow-up, there was a decrease of 1.37 points in the MMSE (p = 0.0002) per unit increase in HbA1c. This result remained essentially unchanged after adjusting also for gender and education (p = 0.0005), cardiovascular factors (p = 0.0003), and lifestyle (p = 0.0006). Additionally, results remained very similar after excluding subjects with potentially incipient diabetes with HbA1c between 6 and 7. These findings suggest that in non-diabetic non-demented elderly subjects, an increase in HbA1c over time is associated with cognitive decline. Such results may have broad clinical applicability since manipulation of glucose control, even in non-diabetics, may affect cognitive performance, perhaps enabling preventive measures against dementia. C1 [Ravona-Springer, Ramit] Chaim Sheba Med Ctr, Ramat Gan, Israel. [Moshier, Erin; Godbold, James] Mt Sinai Sch Med, Dept Prevent Med, New York, NY USA. [Schmeidler, James; Akrivos, Jimmy; Grossman, Hillel T.; Wysocki, Michael; Silverman, Jeremy M.; Haroutunian, Vahram; Beeri, Michal Schnaider] Mt Sinai Sch Med, Dept Psychiat, New York, NY USA. [Rapp, Michael] Humboldt Univ, Dept Psychiat, D-10099 Berlin, Germany. [Grossman, Hillel T.; Silverman, Jeremy M.; Haroutunian, Vahram] James J Peters Vet Affairs Med Ctr, Bronx, NY USA. RP Ravona-Springer, R (reprint author), Chaim Sheba Med Ctr, Memory Clin, IL-52621 Tel Hashomer, Israel. EM ramit.ravona@sheba.health.gov.il FU NIA [K01 AG023515-01, R01 AG034087, P01 AG02219, P50 AG05138]; Irma T. Hirschl award; Berkman Trust; Leir Foundation FX Supported by NIA grants K01 AG023515-01 and R01 AG034087 for Dr. Beeri, P01 AG02219 for Drs. Haroutunian and Schmeidler, and P50 AG05138 for Drs. Sano and Schmeidler, as well as by the Irma T. Hirschl award for Dr. Beeri and the Berkman Trust and Leir Foundation for Dr. Haroutunian. NR 46 TC 31 Z9 31 U1 1 U2 7 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 1387-2877 J9 J ALZHEIMERS DIS JI J. Alzheimers Dis. PY 2012 VL 30 IS 2 BP 299 EP 309 DI 10.3233/JAD-2012-120106 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 947BD UT WOS:000304400700007 PM 22426020 ER PT J AU Trevino, KM Desai, K Lauricella, S Pargament, KI Mahoney, A AF Trevino, Kelly M. Desai, Kavita Lauricella, Shauna Pargament, Kenneth I. Mahoney, Annette TI Perceptions of Lesbian and Gay (LG) Individuals as Desecrators of Christianity as Predictors of Anti-LG Attitudes SO JOURNAL OF HOMOSEXUALITY LA English DT Article DE desecration; gay; lesbian; prejudice; religious coping ID RELIGIOUS FUNDAMENTALISM; PREJUDICE; ADULTS; SAMPLE; ASSOCIATIONS; ORIENTATION; HOMOSEXUALS; PERSONALITY; PREVALENCE; HOMOPHOBIA AB This study applied religious coping theory to examine the relationship between participants' perceptions that lesbian and gay (LG) individuals desecrate Christian values (the stressor) and anti-LG attitudes (the response) and whether religious coping influences the relationship between these variables. Greater agreement with desecration messages was associated with higher levels of anti-LG attitudes. Positive religious coping was associated with lower levels of anti-LG attitudes while negative religious coping was associated with higher levels. Greater exposure to messages that LG individuals desecrate Christian values was associated with greater agreement with those messages. Longitudinal studies with more diverse samples are needed to examine causality and the generalizability of the findings. However, these results have implications for preventing and mitigating anti-LG attitudes. C1 [Trevino, Kelly M.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Desai, Kavita] Univ Michigan Healthcare Syst, Dept Pediat, Ann Arbor, MI USA. [Lauricella, Shauna] CHE Senior Psychol Serv, Brooklyn, NY USA. [Pargament, Kenneth I.; Mahoney, Annette] Bowling Green State Univ, Dept Psychol, Bowling Green, OH 43403 USA. RP Trevino, KM (reprint author), 450 Brookline Ave,Dana 1105, Boston, MA 02215 USA. EM trevino.kelly@gmail.com NR 64 TC 4 Z9 5 U1 3 U2 12 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 0091-8369 J9 J HOMOSEXUAL JI J. Homosex. PY 2012 VL 59 IS 4 BP 535 EP 563 DI 10.1080/00918369.2012.665672 PG 29 WC Psychology, Multidisciplinary; Social Sciences, Interdisciplinary SC Psychology; Social Sciences - Other Topics GA 948XK UT WOS:000304536700002 PM 22500992 ER PT B AU Awad, MM Singh, H Attar, EC AF Awad, Mark M. Singh, Harshabad Attar, Eyal C. BE Batchelor, T DeAngelis, LM TI Overview of the Leukemias SO LYMPHOMA AND LEUKEMIA OF THE NERVOUS SYSTEM, SECOND EDITION LA English DT Editorial Material; Book Chapter ID ACUTE LYMPHOBLASTIC-LEUKEMIA; HEMATOPOIETIC STEM-CELLS; CHEMOTHERAPY; REMISSION; ADHESION; ADULTS; TRIAL C1 [Attar, Eyal C.] Massachusetts Gen Hosp, Ctr Canc, Bone Marrow Transplant Unit, Boston, MA 02114 USA. [Awad, Mark M.] Massachusetts Gen Hosp, Dept Med, Wang Ambulatory Care Ctr, Boston, MA 02114 USA. [Singh, Harshabad] Massachusetts Gen Hosp, Ctr Canc, Ctr Regenerat Med, Boston, MA 02114 USA. RP Attar, EC (reprint author), Massachusetts Gen Hosp, Ctr Canc, Bone Marrow Transplant Unit, Boston, MA 02114 USA. EM mawad1@partners.org; hsingh3@partners.org; eattar@partners.org NR 17 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 978-1-4419-7667-3 PY 2012 BP 41 EP 58 DI 10.1007/978-1-4419-7668-0_2 D2 10.1007/978-1-4419-7668-0 PG 18 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA BAE00 UT WOS:000303896600002 ER PT B AU Ferry, JA Pfannl, R Harris, NL AF Ferry, Judith A. Pfannl, Rolf Harris, Nancy L. BE Batchelor, T DeAngelis, LM TI Pathology of Primary Central Nervous System Lymphoma and Related Conditions SO LYMPHOMA AND LEUKEMIA OF THE NERVOUS SYSTEM, SECOND EDITION LA English DT Article; Book Chapter ID B-CELL LYMPHOMA; PRIMARY CNS LYMPHOMA; PRIMARY INTRAOCULAR LYMPHOMA; OF-THE-LITERATURE; POSTTRANSPLANTATION LYMPHOPROLIFERATIVE DISORDER; NON-HODGKINS-LYMPHOMA; ABERRANT SOMATIC HYPERMUTATION; COLLABORATIVE GROUP-REPORT; IMMUNOCOMPETENT PATIENTS; INTRAVASCULAR LYMPHOMA C1 [Ferry, Judith A.; Harris, Nancy L.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Pfannl, Rolf] Tufts Med Ctr, Dept Pathol, Boston, MA 02111 USA. [Harris, Nancy L.] Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Ferry, JA (reprint author), Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. EM jferry@partners.org; rpfannl@tuftsmedicalcenter.org; nlharris@partners.org NR 123 TC 0 Z9 0 U1 1 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 978-1-4419-7667-3 PY 2012 BP 61 EP 86 DI 10.1007/978-1-4419-7668-0_3 D2 10.1007/978-1-4419-7668-0 PG 26 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA BAE00 UT WOS:000303896600003 ER PT B AU Batchelor, T Neuwelt, E Wang, DL Gonzalez, RG AF Batchelor, Tracy Neuwelt, Edward Wang, Daphne L. Gonzalez, R. Gilberto BE Batchelor, T DeAngelis, LM TI Clinical and Diagnostic Considerations in Primary Central Nervous System Lymphoma SO LYMPHOMA AND LEUKEMIA OF THE NERVOUS SYSTEM, SECOND EDITION LA English DT Article; Book Chapter ID PRIMARY CNS LYMPHOMA; POLYMERASE-CHAIN-REACTION; COLLABORATIVE GROUP-REPORT; CEREBROSPINAL-FLUID CELLS; MALIGNANT-LYMPHOMA; FDG-PET; MENINGEAL DISSEMINATION; COMPUTED-TOMOGRAPHY; BRAIN BIOPSY; MRI FEATURES C1 [Batchelor, Tracy] Harvard Univ, Massachusetts Gen Hosp, Sch Med,Div Hematol & Oncol, Dept Neurol,Stephen E & Catherine Pappas Ctr Neur, Boston, MA 02114 USA. [Batchelor, Tracy] Harvard Univ, Massachusetts Gen Hosp, Sch Med,Div Hematol & Oncol, Dept Radiat Oncol,Stephen E & Catherine Pappas, Boston, MA 02114 USA. [Neuwelt, Edward] Oregon Hlth & Sci Univ, Blood Brain Barrier & Neurooncol Program, Dept Neurol, Portland, OR 97239 USA. [Neuwelt, Edward] Oregon Hlth & Sci Univ, Blood Brain Barrier & Neurooncol Program, Dept Neurosurg, Portland, OR 97239 USA. [Wang, Daphne L.; Gonzalez, R. Gilberto] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Gonzalez, R. Gilberto] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Batchelor, T (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med,Div Hematol & Oncol, Dept Neurol,Stephen E & Catherine Pappas Ctr Neur, 55 Fruit St, Boston, MA 02114 USA. EM thatchelor@partners.org; neuwelte@ohsu.edu; dlwang@partners.org; rggonzalez@partners.org NR 45 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 978-1-4419-7667-3 PY 2012 BP 113 EP 128 DI 10.1007/978-1-4419-7668-0_6 D2 10.1007/978-1-4419-7668-0 PG 16 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA BAE00 UT WOS:000303896600006 ER PT B AU Batchelor, T Grigg, A Thiel, E AF Batchelor, Tracy Grigg, Andrew Thiel, Eckhard BE Batchelor, T DeAngelis, LM TI Chemotherapy for Primary Central Nervous System Lymphoma SO LYMPHOMA AND LEUKEMIA OF THE NERVOUS SYSTEM, SECOND EDITION LA English DT Article; Book Chapter ID PRIMARY CNS LYMPHOMA; HIGH-DOSE METHOTREXATE; RECURRENT PRIMARY CNS; TERM-FOLLOW-UP; PHASE-II; SALVAGE THERAPY; DEFERRED RADIOTHERAPY; INTRAOCULAR LYMPHOMA; PROSPECTIVE TRIAL; ELDERLY-PATIENTS C1 [Batchelor, Tracy] Harvard Univ, Massachusetts Gen Hosp, Sch Med,Div Hematol & Oncol, Dept Neurol,Stephen E & Catherine Pappas Ctr Neur, Boston, MA 02114 USA. [Batchelor, Tracy] Harvard Univ, Massachusetts Gen Hosp, Sch Med,Div Hematol & Oncol, Dept Radiat Oncol,Stephen E & Catherine Pappas Ct, Boston, MA 02114 USA. [Grigg, Andrew] Royal Melbourne Hosp, Melbourne, Vic, Australia. [Thiel, Eckhard] Charite, Dept Hematol & Oncol, D-13353 Berlin, Germany. RP Batchelor, T (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med,Div Hematol & Oncol, Dept Neurol,Stephen E & Catherine Pappas Ctr Neur, 55 Fruit St, Boston, MA 02114 USA. EM tbatchelor@partners.org; andrew.grigg@mh.org.au; eckhard.thiel@charite.de; tbatchelor@partners.org NR 42 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 978-1-4419-7667-3 PY 2012 BP 141 EP 153 DI 10.1007/978-1-4419-7668-0_8 D2 10.1007/978-1-4419-7668-0 PG 13 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA BAE00 UT WOS:000303896600008 ER PT B AU Gerstner, ER Mrugala, MM AF Gerstner, Elizabeth R. Mrugala, Maciej M. BE Batchelor, T DeAngelis, LM TI Neurological Complications of Hodgkin Lymphoma SO LYMPHOMA AND LEUKEMIA OF THE NERVOUS SYSTEM, SECOND EDITION LA English DT Article; Book Chapter ID CENTRAL-NERVOUS-SYSTEM; PARANEOPLASTIC CEREBELLAR DEGENERATION; OF-THE-LITERATURE; PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY; SPINAL-CORD COMPRESSION; GRANULOMATOUS-ANGIITIS; EOSINOPHILIC MENINGITIS; OPHELIA SYNDROME; MEMORY LOSS; DISEASE C1 [Gerstner, Elizabeth R.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Gerstner, Elizabeth R.] Harvard Univ, Sch Med, Boston, MA USA. [Mrugala, Maciej M.] Univ Washington, Fred Hutchinson Canc Res Ctr, Sch Med, Dept Neurol, Seattle, WA 98195 USA. [Mrugala, Maciej M.] Univ Washington, Fred Hutchinson Canc Res Ctr, Sch Med, Dept Neurosurg, Seattle, WA 98195 USA. RP Gerstner, ER (reprint author), Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. EM egerstner@partners.org; mmrugala@u.washington.edu NR 79 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 978-1-4419-7667-3 PY 2012 BP 287 EP 297 DI 10.1007/978-1-4419-7668-0_17 D2 10.1007/978-1-4419-7668-0 PG 11 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA BAE00 UT WOS:000303896600017 ER PT B AU Drappatz, J Jaeckle, KA AF Drappatz, Jan Jaeckle, Kurt A. BE Batchelor, T DeAngelis, LM TI Neurological Complications of Plasma Cell Disorders SO LYMPHOMA AND LEUKEMIA OF THE NERVOUS SYSTEM, SECOND EDITION LA English DT Article; Book Chapter ID SPINAL-CORD COMPRESSION; CENTRAL-NERVOUS-SYSTEM; BING-NEEL-SYNDROME; MULTIPLE-MYELOMA; PERIPHERAL NEUROPATHY; WALDENSTROMS MACROGLOBULINEMIA; HYPERVISCOSITY SYNDROME; MONOCLONAL GAMMOPATHY; POEMS SYNDROME; DEMYELINATING NEUROPATHIES C1 [Drappatz, Jan] Harvard Univ, Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Neurol,Sch Med,Ctr Neurooncol, Boston, MA 02115 USA. [Jaeckle, Kurt A.] Mayo Clin Jacksonville, Dept Oncol, Jacksonville, FL 32224 USA. [Jaeckle, Kurt A.] Mayo Clin Jacksonville, Dept Neurol, Jacksonville, FL 32224 USA. RP Drappatz, J (reprint author), Harvard Univ, Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Neurol,Sch Med,Ctr Neurooncol, Boston, MA 02115 USA. EM jan_drappatz@dfci.harvard.edu; jaeckle.kurt@mayo.edu NR 90 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 978-1-4419-7667-3 PY 2012 BP 299 EP 312 DI 10.1007/978-1-4419-7668-0_18 D2 10.1007/978-1-4419-7668-0 PG 14 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA BAE00 UT WOS:000303896600018 ER PT B AU Quant, EC Fisher, DC Wen, PY AF Quant, Eudocia C. Fisher, David C. Wen, Patrick Y. BE Batchelor, T DeAngelis, LM TI Neurological Complications of Chemotherapy in Lymphoma and Leukemia Patients SO LYMPHOMA AND LEUKEMIA OF THE NERVOUS SYSTEM, SECOND EDITION LA English DT Article; Book Chapter ID CENTRAL-NERVOUS-SYSTEM; PRIMARY CNS LYMPHOMA; ACUTE LYMPHOBLASTIC-LEUKEMIA; HIGH-DOSE METHOTREXATE; CHRONIC LYMPHOCYTIC-LEUKEMIA; CHRONIC MYELOGENOUS LEUKEMIA; PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY; INTRATHECAL CYTOSINE-ARABINOSIDE; NON-HODGKINS-LYMPHOMA; TERM-FOLLOW-UP C1 [Quant, Eudocia C.; Wen, Patrick Y.] Brigham & Womens Hosp, Dept Neurol, Dana Farber Canc Inst, Div Neurooncol,Ctr Neurooncol, Boston, MA 02115 USA. [Fisher, David C.] Brigham & Womens Hosp, Dept Med, Dana Farber Canc Inst, Div Hematol Malignancies, Boston, MA 02115 USA. RP Wen, PY (reprint author), Brigham & Womens Hosp, Dept Neurol, Dana Farber Canc Inst, Div Neurooncol,Ctr Neurooncol, Boston, MA 02115 USA. EM equant@partners.org; david_c_fisher@dfci.harvard.edu; pwen@partners.org NR 184 TC 1 Z9 1 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 978-1-4419-7667-3 PY 2012 BP 357 EP 381 DI 10.1007/978-1-4419-7668-0_22 D2 10.1007/978-1-4419-7668-0 PG 25 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA BAE00 UT WOS:000303896600022 ER PT S AU Bertram, L Tanzi, RE AF Bertram, Lars Tanzi, Rudolph E. BE Teplow, DB TI The Genetics of Alzheimer's Disease SO MOLECULAR BIOLOGY OF NEURODEGENERATIVE DISEASES SE Progress in Molecular Biology and Translational Science LA English DT Review; Book Chapter ID GENOME-WIDE ASSOCIATION; AMYLOID PRECURSOR PROTEIN; DENSITY-LIPOPROTEIN RECEPTOR; BETA-PROTEIN; SUSCEPTIBILITY GENES; IDENTIFIES VARIANTS; MISSENSE MUTATIONS; GAMMA-SECRETASE; RARE VARIANTS; RISK-FACTOR C1 [Bertram, Lars] Max Planck Inst Mol Genet, Dept Vertebrate Genom, D-14195 Berlin, Germany. [Tanzi, Rudolph E.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Genet & Aging Res Unit, Boston, MA USA. RP Bertram, L (reprint author), Max Planck Inst Mol Genet, Dept Vertebrate Genom, Ihnestr 73, D-14195 Berlin, Germany. RI Bertram, Lars/K-3889-2015 OI Bertram, Lars/0000-0002-0108-124X NR 89 TC 81 Z9 82 U1 1 U2 33 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 1877-1173 BN 978-0-12-385883-2 J9 PROG MOL BIOL TRANSL JI Prog. Molec. Biol. Transl. Sci. PY 2012 VL 107 BP 79 EP 100 DI 10.1016/B978-0-12-385883-2.00008-4 PG 22 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA BAD99 UT WOS:000303896500003 PM 22482448 ER PT J AU Lei, XG Wang, XD AF Lei, Xin Gen Wang, Xiaodan BE Hatfield, DL Berry, MJ Gladyshev, VN TI Glutathione Peroxidase 1 and Diabetes SO SELENIUM: ITS MOLECULAR BIOLOGY AND ROLE IN HUMAN HEALTH, THIRD EDITION LA English DT Article; Book Chapter ID PANCREATIC BETA-CELLS; INSULIN GENE-TRANSCRIPTION; SUPEROXIDE-DISMUTASE GENE; INDUCED OXIDATIVE STRESS; PROTEIN-KINASE-B; REACTIVE OXYGEN; VITAMIN-E; HYDROGEN-PEROXIDE; IN-VIVO; RECEPTOR PHOSPHORYLATION AB Discovery of development of type 2 diabetes-like phenotypes in glutathione peroxidase-1 (GPx1) overexpressing mice reveals a novel function of this "oldest" and most abundant selenoprotein in the body. The finding signifies an exciting progress in Se biology, and helps understand metabolic impacts of Se supplementation on human health. While its dual role in coping with reactive oxygen and nitrogen species has received broad recognition, unique functions and mechanisms of GPx1 in beta cell physiology, insulin synthesis and secretion, and body glucose homeostasis are just being unveiled. By modulating intracellular redox status, the GPx1 overproduction or knockout is able to regulate functional expressions of key transcriptional factors or protein in pancreatic islet and insulin-responsive tissues. C1 [Lei, Xin Gen] Cornell Univ, Dept Anim Sci, Ithaca, NY 14853 USA. [Wang, Xiaodan] Harvard Univ, Sch Med, Joslin Diabet Ctr, Dept Med,Sect Islet Cell Biol & Regenerat Med, Boston, MA 02215 USA. RP Lei, XG (reprint author), Cornell Univ, Dept Anim Sci, Ithaca, NY 14853 USA. EM XL20@cornell.edu NR 103 TC 5 Z9 5 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 978-1-4614-1025-6 PY 2012 BP 261 EP 270 DI 10.1007/978-1-4614-1025-6_20 D2 10.1007/978-1-4614-1025-6 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BZZ25 UT WOS:000303410300020 ER PT J AU Yehia, BR Long, JA Stearns, CR French, B Tebas, P Frank, I AF Yehia, Baligh R. Long, Judith A. Stearns, Cordelia R. French, Benjamin Tebas, Pablo Frank, Ian TI Impact of transitioning from HIV clinical trials to routine medical care on clinical outcomes and patient perceptions SO AIDS CARE-PSYCHOLOGICAL AND SOCIO-MEDICAL ASPECTS OF AIDS/HIV LA English DT Article DE HIV; transitions in care; patient perceptions; clinical outcomes; clinical trials ID ACTIVE ANTIRETROVIRAL THERAPY; RANDOMIZED CONTROLLED-TRIAL; SEQUENTIAL 3-DRUG REGIMENS; PROTEASE INHIBITOR THERAPY; CD4 CELL COUNT; INITIAL TREATMENT; VIROLOGICAL RESPONSE; INFECTED PATIENTS; ADHERENCE; PREDICTORS AB Participation in antiretroviral therapy clinical trials (ART-RCTs) offers many advantages including access to new drugs, close monitoring, and cost savings. These same benefits may pose a risk to patients ending ART-RCTs and returning to routine care; as they may experience changes to their drug regimen, decreased monitoring, and new out-of-pocket costs. We aimed to evaluate this transition and determine its effects on viral outcomes and patient perceptions. A retrospective cohort was assembled from participants of naive ART-RCTs at the University of Pennsylvania between 1 January 2000 and 31 December 2009. Data were collected in the 12 months prior to and after trial completion. Multivariable logistic regression was used to evaluate viral failure rates and to identify factors associated with viral failure. Qualitative interviews were held with a subset of patients. Content analysis was used to identify thematic differences between patients with viral failure and those with viral suppression. In total, 116 patients enrolled in 5 ART-RCTs from 2000 to 2009. Viral failure was observed in 39 patients (34%). Nonwhites, high enrollment CD4 count, and trial completion in 1999-2002 were risk factors for failure. Patients transitioning from ART-RCTs to routine care had a 20% increased odds of failure (Adjusted Odds Ratio 1.20 (95% CI[ 0.37, 3.88])). Nine patients with viral suppression and three with viral failure in the year after trail completion were interviewed. Suppressed patients were more eager to continue trial participation, nervous about leaving the trial, and felt prepared to return to routine care. In contrast, those with viral failure were less concerned about the transition. These findings suggest that the posttrial period may be a vulnerable time for patients. Patients without a healthy fear of transitioning from ART-RCTs to routine care may be at increased risk of viral failure. Focus should be given to assisting patients during this transition. C1 [Yehia, Baligh R.; Long, Judith A.; Stearns, Cordelia R.; Tebas, Pablo; Frank, Ian] Univ Penn, Dept Med, Perelman Sch Med, Philadelphia, PA 19104 USA. [Long, Judith A.] Philadelphia Vet Affairs Ctr Hlth Equ Res & Promo, Philadelphia, PA USA. [French, Benjamin] Univ Penn, Dept Biostat & Epidemiol, Perelman Sch Med, Philadelphia, PA 19104 USA. RP Yehia, BR (reprint author), Univ Penn, Dept Med, Perelman Sch Med, Philadelphia, PA 19104 USA. EM byehia@upenn.edu NR 42 TC 1 Z9 1 U1 1 U2 3 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 0954-0121 J9 AIDS CARE JI Aids Care-Psychol. Socio-Med. Asp. Aids-Hiv PY 2012 VL 24 IS 6 BP 769 EP 777 DI 10.1080/09540121.2011.630368 PG 9 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychology, Multidisciplinary; Respiratory System; Social Sciences, Biomedical SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychology; Respiratory System; Biomedical Social Sciences GA 944LS UT WOS:000304204400013 PM 22106980 ER PT S AU Forman, SA Stewart, D AF Forman, Stuart A. Stewart, Deirdre BE Fenton, AW TI Mutations in the GABA(A) Receptor that Mimic the Allosteric Ligand Etomidate SO ALLOSTERY: METHODS AND PROTOCOLS SE Methods in Molecular Biology LA English DT Article; Book Chapter DE GABA-A receptor; Nicotinic acetylcholine receptor; Ion channel; Allosteric model; Etomidate; General anesthesia; Site-directed mutagenesis; Electrophysiology ID GENERAL ANESTHETIC ETOMIDATE; A RECEPTOR; AZI-ETOMIDATE; BINDING-SITE; BENZODIAZEPINES; DESENSITIZATION; MODULATION; ACTIVATION; MECHANISM AB Etomidate is a hydrophobic molecule, a potent general anesthetic, and the best understood drug in this group. Etomidate's target molecules are GABA(A) receptors, its site of action has been identified with photolabeling, and a quantitative allosteric coagonist model has emerged for etomidate effects on GABA(A) receptors. We have shown that when methionine residues that are thought to be adjacent to the etomidate site are mutated to tryptophan, that the bulky hydrophobic side-chains alter mutant GABA(A) receptor function in ways that mimic the effects of etomidate binding to wild-type receptors. Furthermore, these mutations reduce receptor modulation by etomidate. Both of these observations support the hypothesis that these methionine residues form part of the etomidate binding pocket. C1 [Forman, Stuart A.; Stewart, Deirdre] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. RP Forman, SA (reprint author), Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. FU NIGMS NIH HHS [R01 GM089745, P01 GM058448] NR 16 TC 1 Z9 1 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-61779-333-2 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2012 VL 796 BP 317 EP 333 DI 10.1007/978-1-61779-334-9_17 D2 10.1007/978-1-61779-334-9 PG 17 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BAB17 UT WOS:000303686100017 PM 22052498 ER PT J AU Yang, J Karver, MR Li, WL Sahu, S Devaraj, NK AF Yang, Jun Karver, Mark R. Li, Weilong Sahu, Swagat Devaraj, Neal K. TI Metal-Catalyzed One-Pot Synthesis of Tetrazines Directly from Aliphatic Nitriles and Hydrazine SO ANGEWANDTE CHEMIE-INTERNATIONAL EDITION LA English DT Article DE bioorthogonal synthesis; cycloaddition; heterocycles; metal catalysis; tetrazines ID DIELS-ALDER REACTION; ONE-STEP SYNTHESIS; BIOORTHOGONAL REACTION; LIVING CELLS; S-TETRAZINES; CHEMISTRY; 1,2,4,5-TETRAZINES; 3,6-DISUBSTITUTED-1,2,4,5-TETRAZINES; CYCLOADDITION; COMPLEXES C1 [Yang, Jun; Li, Weilong; Sahu, Swagat; Devaraj, Neal K.] Univ Calif San Diego, La Jolla, CA 92093 USA. [Karver, Mark R.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Devaraj, NK (reprint author), Univ Calif San Diego, 9500 Gilman Dr, La Jolla, CA 92093 USA. EM ndevaraj@ucsd.edu RI Yang, Jun/E-8916-2012; Devaraj, Neal/B-4712-2014 FU NIH [K01EB010078]; University of California, San Diego; NSF [CHE-0741968] FX The authors gratefully acknowledge Ralph Mazitschek, Carlos Guerrero, and Scott Hilderbrand for helpful discussions. This material is based upon work supported in part by NIH grant K01EB010078, the University of California, San Diego, and the NSF under CHE-0741968. NR 64 TC 64 Z9 65 U1 7 U2 83 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA BOSCHSTRASSE 12, D-69469 WEINHEIM, GERMANY SN 1433-7851 J9 ANGEW CHEM INT EDIT JI Angew. Chem.-Int. Edit. PY 2012 VL 51 IS 21 BP 5222 EP 5225 DI 10.1002/anie.201201117 PG 4 WC Chemistry, Multidisciplinary SC Chemistry GA 942LG UT WOS:000304044900037 PM 22511586 ER PT S AU Glavis-Bloom, J Muhammed, M Mylonakis, E AF Glavis-Bloom, Justin Muhammed, Maged Mylonakis, Eleftherios BE Mylonakis, E Ausubel, FM Gilmore, M Casadevall, A TI Of Model Hosts and Man: Using Caenorhabditis elegans, Drosophila melanogaster and Galleria mellonella as Model Hosts for Infectious Disease Research SO RECENT ADVANCES ON MODEL HOSTS SE Advances in Experimental Medicine and Biology LA English DT Article; Book Chapter ID ANTIFUNGAL DRUG EFFICACY; INNATE IMMUNE-RESPONSE; CANDIDA-ALBICANS; CRYPTOCOCCUS-NEOFORMANS; VIRULENCE FACTORS; PATHOGENESIS; LARVAE; MECHANISMS; GENETICS; DEFENSE AB The use of invertebrate model hosts has increased in popularity due to numerous advantages of invertebrates over mammalian models, including ethical, logistical and budgetary features. This review provides an introduction to three model hosts, the nematode Caenorhabditis elegans, the fruit fly Drosophila melanogaster and the larvae of Galleria mellonella, the greater wax moth. It highlights principal experimental advantages of each model, for C. elegans the ability to run high-throughput assays, for D. melanogaster the evolutionarily conserved innate immune response, and for G. mellonella the ability to conduct experiments at 37 degrees C and easily inoculate a precise quantity of pathogen. It additionally discusses recent research that has been conducted with each host to identify pathogen virulence factors, study the immune response, and evaluate potential antimicrobial compounds, focusing principally on fungal pathogens. C1 [Mylonakis, Eleftherios] Harvard Univ, Sch Med, Div Infect Dis, Massachusetts Gen Hosp, Boston, MA 02114 USA. [Glavis-Bloom, Justin; Muhammed, Maged] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. RP Mylonakis, E (reprint author), Harvard Univ, Sch Med, Div Infect Dis, Massachusetts Gen Hosp, 55 Fruit St,Gray Jackson 5,Room GRJ-504, Boston, MA 02114 USA. EM emylonakis@partners.org; emylonakis@partners.org OI Glavis-Bloom, Justin/0000-0002-4879-1572 NR 41 TC 39 Z9 39 U1 3 U2 21 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0065-2598 BN 978-1-4419-5637-8 J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 2012 VL 710 BP 11 EP 17 DI 10.1007/978-1-4419-5638-5_2 D2 10.1007/978-1-44195638-8 PG 7 WC Biology; Medicine, Research & Experimental SC Life Sciences & Biomedicine - Other Topics; Research & Experimental Medicine GA BAD93 UT WOS:000303895900002 PM 22127881 ER PT S AU Boyer, L Paquette, N Silverman, N Stuart, LM AF Boyer, Laurent Paquette, Nicholas Silverman, Neal Stuart, Lynda M. BE Mylonakis, E Ausubel, FM Gilmore, M Casadevall, A TI Bacterial Effectors: Learning on the Fly SO RECENT ADVANCES ON MODEL HOSTS SE Advances in Experimental Medicine and Biology LA English DT Article; Book Chapter ID KAPPA-B ACTIVATION; RHO-GTPASES; HELICOBACTER-PYLORI; INNATE IMMUNITY; DROSOPHILA-MELANOGASTER; PATHOGEN RECOGNITION; VIRULENCE FACTORS; DOWN-REGULATION; CELL BIOLOGY; HOST IMMUNE AB A common defining characteristic of pathogenic bacteria is the expression of a repertoire of effector molecules that have been named virulence factors. These bacterial factors include a variety of proteins, such as toxins that are internalized by receptors and translocate across endosomal membranes to reach the cytosol, as well as others that are introduced directly into the cell by means of bacterial secretory apparatuses. Given the importance of these effectors for understanding bacterial pathogenicity, significant effort has been made to dissect their molecular mechanisms of action and their respective roles during infection. Herein we will discuss how Drosophila have been used as a model system to study these important microbial effectors, and to understand their contribution to pathogenicity. C1 [Boyer, Laurent] INSERM, U895, Ctr Mediterraneen Med Mol, F-06204 Nice 3, France. [Boyer, Laurent] Univ Nice Sophia Antipolis, UFR Med, Nice, France. [Paquette, Nicholas; Stuart, Lynda M.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02114 USA. [Silverman, Neal] Univ Massachusetts, Sch Med, Dept Med, Div Infect Dis, Worcester, MA 01605 USA. RP Boyer, L (reprint author), INSERM, U895, Ctr Mediterraneen Med Mol, F-06204 Nice 3, France. EM laurent.boyer@unice.fr RI Boyer, laurent/F-8921-2015; OI Boyer, laurent/0000-0002-1375-1706; Silverman, Neal/0000-0002-4259-456X FU NIAID NIH HHS [AI060025, R01 AI079198, U54 AI057159, AI074958, R01 AI060025] NR 48 TC 2 Z9 2 U1 0 U2 8 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0065-2598 BN 978-1-4419-5637-8 J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 2012 VL 710 BP 29 EP 36 DI 10.1007/978-1-4419-5638-5_4 D2 10.1007/978-1-44195638-8 PG 8 WC Biology; Medicine, Research & Experimental SC Life Sciences & Biomedicine - Other Topics; Research & Experimental Medicine GA BAD93 UT WOS:000303895900004 PM 22127883 ER PT S AU Li, YQ Alam, HB AF Li, Yongqing Alam, Hasan B. BE Mylonakis, E Ausubel, FM Gilmore, M Casadevall, A TI Creating a Pro-survival and Anti-inflammatory Phenotype by Modulation of Acetylation in Models of Hemorrhagic and Septic Shock SO RECENT ADVANCES ON MODEL HOSTS SE Advances in Experimental Medicine and Biology LA English DT Article; Book Chapter ID HISTONE DEACETYLASE INHIBITORS; NF-KAPPA-B; SUBEROYLANILIDE HYDROXAMIC ACID; MULTIPLE ORGAN FAILURE; LEUKOCYTE-ENDOTHELIAL INTERACTIONS; AMYOTROPHIC-LATERAL-SCLEROSIS; SPINAL MUSCULAR-ATROPHY; HEAT-INDUCED APOPTOSIS; TUMOR-NECROSIS-FACTOR; VALPROIC ACID AB Shock, regardless of etiology, is characterized by decreased tissue perfusion resulting in cell death, organ dysfunction, and poor survival. Current therapies largely focus on restoring tissue perfusion through resuscitation but have failed to address the specific cellular dysfunction caused by shock. Acetylation is rapidly emerging as a key mechanism that regulates the expression of numerous genes (epigenetic modulation through activation of nuclear histone proteins), as well as functions of multiple cytoplasmic proteins involved in key cellular functions such as cell survival, repair/healing, signaling, and proliferation. Cellular acetylation can be increased immediately through the administration of histone deacetylase inhibitors (HDACI). A series of studies have been performed using: (1) cultured cells; (2) single-organ ischemia-reperfusion injury models; (3) rodent models of lethal septic and hemorrhagic shock; (4) swine models of lethal hemorrhagic shock and multi-organ trauma; and (5) tissues from severely injured trauma patients, to fully characterize the changes in acetylation that occur following lethal insults and in response to treatment with HDACI. These data demonstrate that: (1) shock causes a decrease in acetylation of nuclear and cytoplasmic proteins; (2) hypoacetylation can be rapidly reversed through the administration of HDACI; (3) normalization of acetylation prevents cell death, decreases inflammation, attenuates activation of pro-apoptotic pathways, and augments pro-survival pathways; (4) the effect of HDACI significantly improves survival in lethal models of septic shock, hemorrhagic shock, and complex poly-trauma without need for conventional fluid resuscitation or blood transfusion; and (5) improvement in survival is not due to better resuscitation but due to an enhanced ability of cells to tolerate lethal insults. As different models of hemorrhagic or septic shock have specific strengths and limitations, this chapter will summarize our attempts to create "pro-survival and anti-inflammatory phenotype" in various models of hemorrhagic shock and septic shock. C1 [Alam, Hasan B.] Massachusetts Gen Hosp, Div Trauma Emergency Surg & Surg Crit Care, Boston, MA 02114 USA. [Li, Yongqing] Harvard Univ, Sch Med, Dept Surg, Div Trauma Emergency Surg & Surg Crit Care,Massac, Boston, MA 02115 USA. RP Alam, HB (reprint author), Massachusetts Gen Hosp, Div Trauma Emergency Surg & Surg Crit Care, 165 Cambridge St,Suite 810, Boston, MA 02114 USA. EM hbalam@partners.org FU NIGMS NIH HHS [R01 GM084127, R0I GM084127] NR 153 TC 22 Z9 24 U1 2 U2 10 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0065-2598 BN 978-1-4419-5637-8 J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 2012 VL 710 BP 107 EP 133 DI 10.1007/978-1-4419-5638-5_11 D2 10.1007/978-1-44195638-8 PG 27 WC Biology; Medicine, Research & Experimental SC Life Sciences & Biomedicine - Other Topics; Research & Experimental Medicine GA BAD93 UT WOS:000303895900011 PM 22127890 ER PT B AU Kaelin, WG AF Kaelin, William G., Jr. BE Figlin, RA Rathmell, WK Rini, BI TI Molecular Biology of Clear Cell Renal Carcinoma SO RENAL CELL CARCINOMA: TRANSLATIONAL BIOLOGY, PERSONALIZED MEDICINE, AND NOVEL THERAPEUTIC TARGETS LA English DT Article; Book Chapter ID HYPOXIA-INDUCIBLE FACTOR; HIPPEL-LINDAU GENE; GROWTH-FACTOR RECEPTOR; TUMOR-SUPPRESSOR GENE; PHASE-II TRIAL; PAS DOMAIN PROTEIN; HIF-1 TRANSCRIPTIONAL ACTIVITY; BIOLOGICALLY-ACTIVE PRODUCT; COPY-NUMBER ALTERATIONS; B-CHAIN GENE C1 [Kaelin, William G., Jr.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. [Kaelin, William G., Jr.] Brigham & Womens Hosp, Boston, MA 02215 USA. [Kaelin, William G., Jr.] Howard Hughes Med Inst, Chevy Chase, MD 20815 USA. RP Kaelin, WG (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. EM william_kaelin@dfci.harvard.edu NR 174 TC 1 Z9 1 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 978-1-4614-2399-7 PY 2012 BP 27 EP 47 DI 10.1007/978-1-4614-2400-0_2 D2 10.1007/978-1-4615-2400-0 PG 21 WC Oncology SC Oncology GA BZZ35 UT WOS:000303413500002 ER PT B AU Bahamon, B Signoretti, S AF Bahamon, Brittany Signoretti, Sabina BE Figlin, RA Rathmell, WK Rini, BI TI Tissue Biomarkers in Renal Cell Carcinoma: Intermediate Endpoints in the Selection of Targeted Agents for RCC SO RENAL CELL CARCINOMA: TRANSLATIONAL BIOLOGY, PERSONALIZED MEDICINE, AND NOVEL THERAPEUTIC TARGETS LA English DT Article; Book Chapter ID CARBONIC-ANHYDRASE-IX; TUMOR-SUPPRESSOR GENE; PARAFFIN-EMBEDDED TISSUE; HIPPEL-LINDAU-DISEASE; PATHOLOGISTS GUIDELINE RECOMMENDATIONS; MARKER-IMMUNOSTAINING INTENSITY; IN-SITU HYBRIDIZATION; BREAST-CANCER; KIDNEY CANCER; VHL GENE C1 [Bahamon, Brittany; Signoretti, Sabina] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Signoretti, Sabina] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Signoretti, S (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Pathol, 75 Francis St, Boston, MA 02115 USA. EM ssignoretti@partners.org NR 129 TC 3 Z9 3 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 978-1-4614-2399-7 PY 2012 BP 69 EP 89 DI 10.1007/978-1-4614-2400-0_4 D2 10.1007/978-1-4615-2400-0 PG 21 WC Oncology SC Oncology GA BZZ35 UT WOS:000303413500004 ER PT J AU Zou, L Feng, Y Li, Y Zhang, M Chen, C Chao, W AF Zou, L. Feng, Y. Li, Y. Zhang, M. Chen, C. Chao, W. TI COMPLEMENT FACTOR B EXPRESSION IS REGULATED BY TOLL-LIKE RECEPTORS AND PLAYS AN IMPORTANT ROLE IN EXPERIMENTAL POLYMICROBIAL SEPSIS SO SHOCK LA English DT Meeting Abstract CT 7th Congress of the International-Federation-of-Shock-Societies/35th Annual Conference on Shock CY JUN 09-13, 2012 CL Miami Beach, FL SP Int Federat Shock Soc C1 [Zou, L.; Feng, Y.; Li, Y.; Zhang, M.; Chen, C.; Chao, W.] 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 1073-2322 J9 SHOCK JI Shock PY 2012 VL 37 SU 1 BP 18 EP 19 PG 2 WC Critical Care Medicine; Hematology; Surgery; Peripheral Vascular Disease SC General & Internal Medicine; Hematology; Surgery; Cardiovascular System & Cardiology GA 946VL UT WOS:000304385500021 ER PT J AU Osuka, A Yamada, M Stoecklein, VM Kaneki, M Lederer, J AF Osuka, A. Yamada, M. Stoecklein, V. M. Kaneki, M. Lederer, J. TI IMMUNE-ENHANCING PROPERTIES OF STATIN AND COENZYME Q10 TREATMENT IN SEPSIS SO SHOCK LA English DT Meeting Abstract CT 7th Congress of the International-Federation-of-Shock-Societies/35th Annual Conference on Shock CY JUN 09-13, 2012 CL Miami Beach, FL SP Int Federat Shock Soc C1 [Osuka, A.; Stoecklein, V. M.; Lederer, J.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. [Yamada, M.; Kaneki, M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Osuka, A.] Social Insurance Chukyo Hosp, Nagoya, Aichi, Japan. NR 0 TC 0 Z9 0 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1073-2322 J9 SHOCK JI Shock PY 2012 VL 37 SU 1 BP 22 EP 22 PG 1 WC Critical Care Medicine; Hematology; Surgery; Peripheral Vascular Disease SC General & Internal Medicine; Hematology; Surgery; Cardiovascular System & Cardiology GA 946VL UT WOS:000304385500029 ER PT J AU Fu, M Yamada, M Kaneki, M AF Fu, M. Yamada, M. Kaneki, M. TI BURN INJURY-INDUCED SKELETAL MUSCLE INSULIN RESISTANCE IS ASSOCIATED WITH DECREASED MITOCHONDRIAL BIOGENESIS IN MICE SO SHOCK LA English DT Meeting Abstract CT 7th Congress of the International-Federation-of-Shock-Societies/35th Annual Conference on Shock CY JUN 09-13, 2012 CL Miami Beach, FL SP Int Federat Shock Soc C1 [Fu, M.; Yamada, M.; Kaneki, M.] Harvard Univ, Massachusetts Gen Hosp, Shriners Hosp Children, Sch Med, Charlestown, 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 1073-2322 J9 SHOCK JI Shock PY 2012 VL 37 SU 1 BP 91 EP 91 PG 1 WC Critical Care Medicine; Hematology; Surgery; Peripheral Vascular Disease SC General & Internal Medicine; Hematology; Surgery; Cardiovascular System & Cardiology GA 946VL UT WOS:000304385500236 ER PT J AU Tanguturi, VK Noseworthy, PA Newton-Cheh, C Baggish, AL AF Tanguturi, Varsha Keelara Noseworthy, Peter A. Newton-Cheh, Christopher Baggish, Aaron L. TI The Electrocardiographic Early Repolarization Pattern in Athletes Normal Variant or Sudden Death Risk Factor? SO SPORTS MEDICINE LA English DT Article ID ST-SEGMENT ELEVATION; J-WAVE SYNDROMES; BRUGADA-SYNDROME; VENTRICULAR-FIBRILLATION; INFERIOR LEADS; 12-LEAD ELECTROCARDIOGRAM; CELLULAR BASIS; ABNORMALITIES; POPULATION; MECHANISMS AB The clinical evaluation of athletes during symptom evaluation or preparticipation screening often involves interpretation of the 12-lead electrocardiogram (ECG). Differentiating abnormal ECG findings suggestive of underlying cardiovascular disease from benign findings caused by exercise-induced cardiac adaptations can be challenging, and recent clinical guidelines have been created for this purpose. One of the most common ECG findings in athletes is the early repolarization pattern (ERP), characterized by diffuse J-point elevation and concave ST-segment elevation, and long regarded as a normal variant. However, recently published data suggest that the ERP may be a marker of increased risk for sudden cardiac death (SCD) in the general population. The observation that the ERP can indicate increased SCD risk has important implications for the clinician charged with the care of athletes. This review will describe the evolving understanding of the ERP and will explore the relevance of the ERP for the care of athletes. C1 [Baggish, Aaron L.] Massachusetts Gen Hosp, Cardiovasc Performance Program, Div Cardiol, Cardiol Res Ctr, Boston, MA 02114 USA. [Tanguturi, Varsha Keelara] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Noseworthy, Peter A.; Newton-Cheh, Christopher; Baggish, Aaron L.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Div Cardiol, Boston, MA 02114 USA. [Baggish, Aaron L.] Harvard Univ Hlth Serv, Cambridge, MA USA. RP Baggish, AL (reprint author), Massachusetts Gen Hosp, Cardiovasc Performance Program, Div Cardiol, Cardiol Res Ctr, Yawkey Suite 5B,55 Fruit St, Boston, MA 02114 USA. EM abaggish@partners.org NR 45 TC 9 Z9 9 U1 0 U2 6 PU ADIS INT LTD PI AUCKLAND PA 41 CENTORIAN DR, PRIVATE BAG 65901, MAIRANGI BAY, AUCKLAND 1311, NEW ZEALAND SN 0112-1642 J9 SPORTS MED JI Sports Med. PY 2012 VL 42 IS 5 BP 359 EP 366 PG 8 WC Sport Sciences SC Sport Sciences GA 943MM UT WOS:000304127700001 PM 22468694 ER PT J AU Chen, HH Yuan, HS Josephson, L Sosnovik, DE AF Chen, Howard H. Yuan, Hushan Josephson, Lee Sosnovik, David E. TI Theranostic Imaging of the Kinases and Proteases that Modulate Cell Death and Survival SO THERANOSTICS LA English DT Review DE Molecular Imaging; Theranostic; Cell Death; Apoptosis; PI3K ID POSITRON-EMISSION-TOMOGRAPHY; ACTIVATING VIRIDIN PRODRUG; IN-VIVO; ISCHEMIA/REPERFUSION INJURY; PHOSPHOINOSITIDE 3-KINASE; NONINVASIVE DETECTION; CARDIAC-FUNCTION; AKT ACTIVATION; ANNEXIN-V; APOPTOSIS AB Several signaling cascades are involved in cell death, with a significant amount of crosstalk between them. Despite the complexity of these cascades several key pro-survival and pro-death players have been identified. These include PI3-kinase, AKT and caspase-3. Here we review the approaches used to date to perform molecular imaging of these important targets. We focus in particular on approaches that include the possibility of modulating the activity of these kinases and proteases in a theranostic approach. C1 [Chen, Howard H.; Josephson, Lee; Sosnovik, David E.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Martinos Ctr Biomed Imaging, Boston, MA USA. [Chen, Howard H.; Sosnovik, David E.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Mol Imaging Res, Boston, MA USA. [Yuan, Hushan; Josephson, Lee] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Translat Nucl Med & Mol Imaging, Boston, MA USA. RP Sosnovik, DE (reprint author), 149 13th St, Charlestown, MA 02129 USA. EM sosnovik@nmr.mgh.harvard.edu FU NIH [R01HL093038] FX This work was funded in part by the following NIH grants: R01HL093038. NR 40 TC 5 Z9 5 U1 2 U2 19 PU IVYSPRING INT PUBL PI LAKE HAVEN PA PO BOX 4546, LAKE HAVEN, NSW 2263, AUSTRALIA SN 1838-7640 J9 THERANOSTICS JI Theranostics PY 2012 VL 2 IS 2 BP 148 EP 155 DI 10.7150/thno.4077 PG 8 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 942FN UT WOS:000304029500004 PM 22400062 ER PT J AU Habibollahi, P Figueiredo, JL Heidari, P Dulak, AM Imamura, Y Bass, AJ Ogino, S Chan, AT Mahmood, U AF Habibollahi, Peiman Figueiredo, Jose-Luiz Heidari, Pedram Dulak, Austin M. Imamura, Yu Bass, Adam J. Ogino, Shuji Chan, Andrew T. Mahmood, Umar TI Optical Imaging with a Cathepsin B Activated Probe for the Enhanced Detection of Esophageal Adenocarcinoma by Dual Channel Fluorescent Upper GI Endoscopy SO THERANOSTICS LA English DT Article DE Esophageal Adenocarcinoma; Cathepsin B; Prosense750; Near Infrared Imaging ID OVARIAN-CANCER METASTASES; BARRETTS-ESOPHAGUS; AMPLICON; GENE; SURVEILLANCE; EXPRESSION; CARCINOMA; MICE AB Despite significant advances in diagnosis and treatment, the prognosis of esophageal adenocarcinoma remains poor highlighting the importance of early detection. Although white light (WL) upper endoscopy can be used for screening of the esophagus, it has limited sensitivity for early stage disease. Thus, development of new imaging technology to improve the diagnostic capabilities of upper GI endoscopy for early detection of esophageal adenocarcinoma is an important unmet need. The goal of this study was to develop a method for the detection of malignant lesions in the esophagus using WL upper endoscopy combined with near infrared (NIR) imaging with a protease activatable probe (Prosense750) selective for cathepsin B (CTSB). An orthotopic murine model for distal esophageal adenocarcinoma was generated through the implantation of OE-33 and OE-19 human esophageal adenocarcinoma lines in immunocompromised mice. The mice were imaged simultaneously for WL and NIR signal using a custom-built dual channel upper GI endoscope. The presence of tumor was confirmed by histology and target to background ratios (TBR) were compared for both WL and NIR imaging. NIR imaging with ProSense750 significantly improved upon the TBRs of esophageal tumor foci, with a TBR of 3.64 +/- 0.14 and 4.50 +/- 0.11 for the OE-33 and OE-19 tumors respectively, compared to 0.88 +/- 0.04 and 0.81 +/- 0.02 TBR for WL imaging. The combination of protease probes with novel imaging devices has the potential to improve esophageal tumor detection by fluorescently highlighting neoplastic regions. C1 [Habibollahi, Peiman; Heidari, Pedram; Mahmood, Umar] Harvard Univ, Sch Med, Dept Radiol, Div Nucl Med & Mol Imaging,Massachusetts Gen Hosp, Boston, MA 02115 USA. [Figueiredo, Jose-Luiz] Harvard Univ, Sch Med, Dept Med, Div Cardiovasc Med,Brigham & Womens Hosp, Boston, MA USA. [Dulak, Austin M.; Bass, Adam J.; Ogino, Shuji] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Imamura, Yu; Ogino, Shuji] Harvard Univ, Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Chan, Andrew T.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastrointestinal Unit, Boston, MA USA. RP Mahmood, U (reprint author), Harvard Univ, Sch Med, Dept Radiol, Div Nucl Med & Mol Imaging,Massachusetts Gen Hosp, Boston, MA 02115 USA. EM umahmood@mgh.harvard.edu FU National Health Institute [U01CA143056, U01CA084301, P50CA127003] FX This research was supported in part by National Health Institute grants U01CA143056, U01CA084301 and P50CA127003. NR 20 TC 20 Z9 20 U1 3 U2 12 PU IVYSPRING INT PUBL PI LAKE HAVEN PA PO BOX 4546, LAKE HAVEN, NSW 2263, AUSTRALIA SN 1838-7640 J9 THERANOSTICS JI Theranostics PY 2012 VL 2 IS 2 BP 227 EP 234 DI 10.7150/thno.4088 PG 8 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 942FN UT WOS:000304029500011 PM 22400064 ER PT J AU Brawner, BM Gomes, MM Jemmott, LS Deatrick, JA Coleman, CL AF Brawner, B. M. Gomes, M. M. Jemmott, L. S. Deatrick, J. A. Coleman, C. L. TI Clinical depression and HIV risk-related sexual behaviors among African-American adolescent females: Unmasking the numbers SO AIDS CARE-PSYCHOLOGICAL AND SOCIO-MEDICAL ASPECTS OF AIDS/HIV LA English DT Article DE HIV/AIDS; depression; adolescents; African-American; mixed methods ID RANDOMIZED CONTROLLED-TRIAL; REDUCTION INTERVENTIONS; PSYCHIATRIC OUTPATIENTS; SUBSTANCE USE; SYMPTOMS; VALIDITY; PHQ-9; PREDICTORS; INFECTION; ADULTS AB Clinically depressed and nondepressed African-American adolescent females aged 13-19 years (N = 131) were interviewed and surveyed to determine the relationship between depression and HIV risk-related sexual behaviors. Narratives indicate that the psychopathology ofdepression may create situations where the target population could become exposed to HIV. Specifically, depressed participants described feelings of loneliness, isolation, and wanting somebody to "comfort them" as aspects of depression that affect the decisions they make about sex and relationships. In essence, sex was viewed as a stress reliever, an anti-depressant and a way to increase self-esteem. They shared that even if they did not feel like having sex, they might just "git it over wit" so their partners would stop asking. Some also discussed financial and emotional stability offered by older, more sexually experienced partners. These age-discordant relationships often translated into trusting that their partners knew what was best for their sexual relationships (i.e., having unprotected sex). Sixty-nine percent (n = 88) of the sample reported engaging in sexual activity. Given their mean age (16 +/- 1.9 years) participants had been sexually active for 2 +/- 1.8 years. The adolescents reported an average of 2 +/- 1.8 sexual partners within the past three months. Depressed participants reported a higher frequency of having ever had sex (78% vs. 59%, chi(2) = 5.236, p = 0.022), and had a higher mean number ofsexual partners (2 vs. 1, t = - 2.023, p = 0.048) and sexual encounters under the influence of drugs and alcohol (8 vs. 2, t = - 3.078, p = 0.005) in the past three months. The results of this study can guide the modification and/or development of tailored HIV/sexually transmitted infection (STI) prevention programs. The findings provide explicit, psychologically and culturally relevant information regarding the interaction between depression, self-medicating behaviors and risk for HIV/STIs among clinically depressed African-American adolescent females. C1 [Brawner, B. M.; Jemmott, L. S.; Deatrick, J. A.; Coleman, C. L.] Univ Penn, Sch Nursing, Ctr Hlth Equ Res, Philadelphia, PA 19104 USA. [Gomes, M. M.] Virginia Commonwealth Univ, Sch Nursing, Richmond, VA USA. RP Brawner, BM (reprint author), Univ Penn, Sch Nursing, Ctr Hlth Equ Res, Philadelphia, PA 19104 USA. EM brawnerb@nursing.upenn.edu FU CMHS SAMHSA HHS [5SM058566-02]; NINR NIH HHS [P20 NR008361, P20 NR008361-05, P20NR008361] NR 40 TC 14 Z9 14 U1 2 U2 8 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 0954-0121 J9 AIDS CARE JI Aids Care-Psychol. Socio-Med. Asp. Aids-Hiv PY 2012 VL 24 IS 5 BP 618 EP 625 DI 10.1080/09540121.2011.630344 PG 8 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychology, Multidisciplinary; Respiratory System; Social Sciences, Biomedical SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychology; Respiratory System; Biomedical Social Sciences GA 936AK UT WOS:000303563100011 PM 22292603 ER PT J AU Kindy, MS Yu, J Zhu, H El-Amouri, SS Hook, V Hook, GR AF Kindy, Mark S. Yu, Jin Zhu, Hong El-Amouri, Salim S. Hook, Vivian Hook, Gregory R. TI Deletion of the Cathepsin B Gene Improves Memory Deficits in a Transgenic Alzheimer's Disease Mouse Model Expressing A beta PP Containing the Wild-Type beta-Secretase Site Sequence SO JOURNAL OF ALZHEIMERS DISEASE LA English DT Article DE Amyoid-beta; amyoid-beta protein precursor; cathepsin B; gene knockout; protease ID AMYLOID PRECURSOR PROTEIN; IN-VIVO; SYNAPTIC PLASTICITY; PARTIAL REDUCTION; MESSENGER-RNA; MICE; BACE1; BRAIN; INHIBITORS; ENZYME AB Therapeutic agents that improve the memory loss of Alzheimer's disease (AD) may eventually be developed if drug targets are identified that improve memory deficits in appropriate AD animal models. One such target is beta-secretase which, in most AD patients, cleaves the wild-type (WT) beta-secretase site sequence of the amyloid-beta protein precursor (A beta PP) to produce neurotoxic amyloid-beta (A beta). Thus, an animal model representing most AD patients for evaluating beta-secretase effects on memory deficits is one that expresses human A beta PP containing the WT beta-secretase site sequence. BACE1 and cathepsin B (CatB) proteases have beta-secretase activity, but gene knockout studies have not yet validated that the absence of these proteases improves memory deficits in such an animal model. This study assessed the effects of deleting these protease genes on memory deficits in the AD mouse model expressing human A beta PP containing the WT beta-secretase site sequence and the London gamma-secretase site (A beta PPWT/Lon mice). Knockout of the CatB gene in the A beta PPWT/Lon mice improved memory deficits and altered the pattern of A beta-related biomarkers in a manner consistent with CatB having WT beta-secretase activity. But deletion of the BACE1 gene had no effect on these parameters in the A beta PPWT/Lon mice. These data are the first to show that knockout of a putative beta-secretase gene results in improved memory in an AD animal model expressing the WT beta-secretase site sequence of A beta PP, present in the majority of AD patients. CatB may be an effective drug target for improving memory deficits in most AD patients. C1 [Kindy, Mark S.; Yu, Jin; Zhu, Hong] Med Univ S Carolina, Dept Neurosci, Charleston, SC 29425 USA. [Kindy, Mark S.] Ralph H Johnson VA Med Ctr, Charleston, SC USA. [Kindy, Mark S.] Appl Neurotechnol Inc, Charleston, SC USA. [El-Amouri, Salim S.] Univ Cincinnati, Cincinnati Childrens Hosp Med Ctr, Div Expt Hematol, Cincinnati, OH USA. [Hook, Vivian] Univ Calif San Diego, Skaggs Sch Pharm & Pharmaceut Sci, La Jolla, CA 92093 USA. [Hook, Vivian] Univ Calif San Diego, Dept Neurosci, La Jolla, CA 92093 USA. [Hook, Vivian] Univ Calif San Diego, Dept Pharmacol, La Jolla, CA 92093 USA. [Hook, Vivian] Univ Calif San Diego, Dept Med, La Jolla, CA 92093 USA. [Hook, Gregory R.] Amer Life Sci Pharmaceut, San Diego, CA USA. RP Kindy, MS (reprint author), Med Univ S Carolina, Dept Neurosci, 114 Doughty St,Room 503, Charleston, SC 29425 USA. EM kindyms@musc.edu FU National Institute on Aging, National Institutes of Health, Bethesda, MD [R21 AG0311963, R44 AG030865, R44 AG032784]; Alzheimer's Drug Discovery Foundation, New York City, NY [20100304]; Alzheimer's Association FX This work was supported by grants R21 AG0311963, R44 AG030865, and R44 AG032784 from the National Institute on Aging, National Institutes of Health, Bethesda, MD, and grant no. 20100304 from the Alzheimer's Drug Discovery Foundation, New York City, NY to American Life Science Pharmaceuticals (ALSP), and a grant from the Alzheimer's Association to Dr. Vivian Hook. NR 41 TC 17 Z9 17 U1 0 U2 3 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 1387-2877 J9 J ALZHEIMERS DIS JI J. Alzheimers Dis. PY 2012 VL 29 IS 4 BP 827 EP 840 DI 10.3233/JAD-2012-111604 PG 14 WC Neurosciences SC Neurosciences & Neurology GA 937RC UT WOS:000303674900011 PM 22337825 ER PT J AU Messmer-Blust, AF Zhang, CL Shie, JL Song, QH He, P Lubenec, I Liu, YH Sellke, F Li, J AF Messmer-Blust, Angela F. Zhang, Cuili Shie, Jue-Lon Song, Qinhui He, Ping Lubenec, Isabel Liu, Yuhong Sellke, Frank Li, Jian TI Related Transcriptional Enhancer Factor 1 Increases Endothelial-Dependent Microvascular Relaxation and Proliferation SO JOURNAL OF VASCULAR RESEARCH LA English DT Article DE Fibroblast growth factor receptor 1; Related transcriptional enhancer factor 1; Endothelial nitric oxide synthase; Endothelial function; Microvascular relaxation ID FIBROBLAST-GROWTH-FACTOR; SMOOTH-MUSCLE-CELLS; TRANSGENIC MICE; FACTOR RECEPTOR-1; ANGIOGENESIS; EXPRESSION; RTEF-1; VEGF; MYOCARDIUM; MATRIX AB Objective: Related transcriptional enhancer factor 1 (RTEF-1) is a key transcriptional regulator in endothelial function. In this study, we investigated a possible role for RTEF-1 in the regulation of microvascular relaxation and the underlying mechanism involved. Activation of fibroblast growth factor receptor 1 (FGFR1) by FGFs increases vasodilation, although transcriptional control of the molecular mechanisms underlying FGFR1 is still unclear. Materials and Methods:We demonstrated that RTEF-1 stimulated FGFR1 expression at the transcriptional level, specifically an area including Sp1 elements, as evidenced by promoter assays. Additionally, RTEF-1 increased FGFR1 mRNA and protein expression in vitro and in VE-cadherin-promoted RTEF-1 (VE-Cad/RTEF-1) transgenic mice, whereas RTEF-1 siRNA blocked the upregulation of FGFR1 expression. Furthermore, increased endothelial-dependent microvessel relaxation was observed in the coronary arteries of VE-Cad/RTEF-1 mice, and increased proliferation was observed in RTEF-1-overexpressing cells, both of which correlated to increased FGF/FGFR1 signaling and endothelial nitric oxide synthase (eNOS) upregulation. Our results indicate that RTEF-1 acts as a transcriptional stimulator of FGFR1 and is involved in FGF pathways by increasing microvessel dilatation via eNOS. Conclusions: These findings suggest that RTEF-1 plays an important role in FGFR1-stimulated vasodilatation. Understanding the effect of RTEF-1 in microvessel relaxation may provide beneficial knowledge in improving treatments in regards to ischemic vascular disorders. Copyright (C) 2012 S. Karger AG, Basel C1 [Li, Jian] Harvard Univ, Sch Med, Div Cardiovasc Med, Beth Israel Deaconess Med Ctr,Ctr Life Sci Bldg, Boston, MA 02115 USA. [Liu, Yuhong; Sellke, Frank] Brown Univ, Rhode Isl Hosp, Div Cardiothorac Surg, Providence, RI 02903 USA. [Liu, Yuhong; Sellke, Frank] Brown Univ, Alpert Med Sch, Providence, RI 02912 USA. [Zhang, Cuili] Harbin Med Univ, Affiliated Hosp 1, Dept Cardiol, Harbin, Peoples R China. RP Li, J (reprint author), Harvard Univ, Sch Med, Div Cardiovasc Med, Beth Israel Deaconess Med Ctr,Ctr Life Sci Bldg, 3 Blackfan Circle, Boston, MA 02115 USA. EM jli@bidmc.harvard.edu FU NIH [R01HL082837, R01HL69024, T32HL007374] FX We would like to thank Dr. Alex Stewart (University of Ottawa, Canada) for providing the RTEF-1 expression vector and Dr. Pablo Quintero Pinzon for helpful discussions regarding the manuscript. This study was supported by NIH R01HL082837 (J.L.), NIH R01HL69024 (F.S.) and by an NIH training grant T32HL007374 (A.F.M.-B.). NR 26 TC 6 Z9 6 U1 0 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1018-1172 J9 J VASC RES JI J. Vasc. Res. PY 2012 VL 49 IS 3 BP 249 EP 259 DI 10.1159/000335180 PG 11 WC Physiology; Peripheral Vascular Disease SC Physiology; Cardiovascular System & Cardiology GA 941MS UT WOS:000303967900007 PM 22433836 ER PT J AU Husk, JS Farivar, R Hess, RF AF Husk, Jesse S. Farivar, Reza Hess, Robert F. TI Amblyopic deficits in processing structure-from-motion SO JOURNAL OF VISION LA English DT Article DE amblyopic deficits; structure-from-motion; extrastriate processing ID STRABISMIC AMBLYOPIA; GLOBAL MOTION; ORIENTATION INFORMATION; ANISOMETROPIC AMBLYOPIA; FELLOW EYE; PERCEPTION; INTEGRATION; FORM; AREA; 3D AB Amblyopic observers exhibit a range of low-and high-level cortical deficits, and there is strong evidence that the extrastriate cortex is selectively affected for signal/noise tasks but not for simple integration tasks. We tested amblyopic and control observers on a structure-from-motion (SFM) task involving signal integration to gauge whether extrastriate processing is compromised at a level where dorsal and ventral information is combined. SFM tasks require integration of local elements to perceive the global structure using motion-defined depth cues. Observers were monocularly presented with a 2-IFC shape discrimination task and asked to indicate whether two consecutive SFM stimuli represented the same or different depth-defined shapes. Amblyopic observers had higher depth thresholds than control observers, even after controlling for low-level differences in contrast thresholds across eyes and observers. Combined with the presence of the deficit in both the amblyopic and fellow-fixing eyes, this suggests a high-level locus for the SFM deficit. C1 [Husk, Jesse S.; Farivar, Reza; Hess, Robert F.] McGill Univ, McGill Vis Res Unit, Dept Ophthalmol, Montreal, PQ H3X 2E9, Canada. [Farivar, Reza] Massachusetts Gen Hosp, A Athinoula Martinos Ctr Biomed Imaging, Boston, MA 02114 USA. [Farivar, Reza] Harvard Univ, Sch Med, Boston, MA USA. RP Husk, JS (reprint author), McGill Univ, McGill Vis Res Unit, Royal Victoria Hosp, Montreal, PQ H3X 2E9, Canada. EM jesse.husk@mail.mcgill.ca RI Hess, Robert/A-5624-2008 FU CIHR [MOP10818] FX This research was supported by CIHR Grant MOP10818 awarded to Dr. Robert Hess. NR 44 TC 5 Z9 5 U1 1 U2 4 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 1534-7362 J9 J VISION JI J. Vision PY 2012 VL 12 IS 4 AR 4 DI 10.1167/12.4.4 PG 12 WC Ophthalmology SC Ophthalmology GA 940RI UT WOS:000303910300004 ER PT J AU Friedlander, AH Lopez-Lopez, J Velasco-Ortega, E AF Friedlander, Arthur H. Lopez-Lopez, Jose Velasco-Ortega, Eugenio TI Diagonal ear lobe crease and atherosclerosis: A review of the medical literature and dental implications SO MEDICINA ORAL PATOLOGIA ORAL Y CIRUGIA BUCAL LA English DT Article DE Diagonal ear lobe crease; atherosclerosis disease; calcified carotid artery; atheromas; panoramic radiographs ID CORONARY-ARTERY-DISEASE; EARLOBE CREASE; CARDIOVASCULAR-DISEASE; HEART-DISEASE; RISK-FACTORS; ALL-CAUSE; THICKNESS; ASSOCIATION; MORTALITY; DEATH AB In Spain a significant number of individuals die from atherosclerotic disease of the coronary and carotid arteries without having classic risk factors and prodromal symptoms. The diagonal ear lobe crease (DELC) has been characterized in the medical literature as a surrogate marker which can identify high risk patients having occult atherosclerosis. This topic however has not been examined in either the medical or dental literature emanating from Spain. The majority of clinical, angiography and postmortem reports support the premise that DELC is a valuable extravascular physical sign able to distinguish some patients at risk of succumbing to atherosclerosis of the coronary arteries. A minority of studies have however failed to support this hypothesis. More recently reports using B mode ultrasound have also linked DELC to atherosclerosis of the carotid artery and another report has related DELC to the presence of calcified carotid artery atheromas on panoramic radiographs. DELC is readily visible during head and neck cancer screening examinations. In conjunction with the patient's medical history, vital signs, and panoramic radiograph, the DELC may assist in atherosclerotic risk assessment. C1 [Friedlander, Arthur H.] VA Greater Los Angeles Healthcare Syst, Grad Med Educ, Los Angeles, CA USA. [Friedlander, Arthur H.] UCLA Med Ctr, Hosp Dent Serv, Los Angeles, CA USA. [Friedlander, Arthur H.] Univ Calif Los Angeles, Sch Dent, Los Angeles, CA 90024 USA. [Lopez-Lopez, Jose] Univ Barcelona, Sch Dent, Dept Stomatol, Catalonia, Spain. [Velasco-Ortega, Eugenio] Univ Seville, Dept Stomatol, Sch Dent, Andalucia, Spain. RP Lopez-Lopez, J (reprint author), Dept Odontostomatol, Bellvitge Univ Campus,Pabellon Gobierno 2A Planta, Barcelona 08907, Spain. EM 18575jll@gmail.com NR 39 TC 6 Z9 7 U1 0 U2 2 PU MEDICINA ORAL S L PI VALENCIA PA CALLE DANIEL BALACIART N 4 PTA 17, VALENCIA, 46020, SPAIN SN 1698-4447 J9 MED ORAL PATOL ORAL JI Med. Oral Patol. Oral Cir. Bucal PD JAN PY 2012 VL 17 IS 1 BP E153 EP E159 AR 17390 DI 10.4317/medoral.17390 PG 7 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 936SH UT WOS:000303609800026 PM 21743392 ER PT J AU Atri, A Rountree, SD Lopez, OL Doody, RS AF Atri, Alireza Rountree, Susan D. Lopez, Oscar L. Doody, Rachelle S. TI Validity, Significance, Strengths, Limitations, and Evidentiary Value of Real-World Clinical Data for Combination Therapy in Alzheimer's Disease: Comparison of Efficacy and Effectiveness Studies SO NEURODEGENERATIVE DISEASES LA English DT Article; Proceedings Paper CT 10th International Conference on Alzheimers and Parkinsons Diseases (AD/PD) CY MAR 09-13, 2011 CL Barcelona, SPAIN DE Comparative effectiveness; Evidence grade; Dementia treatment; Donepezil; Galantamine; Rivastigmine; Memantine; Observational trial ID RANDOMIZED CONTROLLED-TRIAL; PLACEBO-CONTROLLED TRIAL; MEMANTINE TREATMENT; DOUBLE-BLIND; OPEN-LABEL; MODERATE; DONEPEZIL; GALANTAMINE; MULTICENTER; EXTENSION AB Background: Randomized controlled efficacy trials (RCTs), the scientific gold standard, are required for regulatory approval of Alzheimer's disease (AD) interventions, yet provide limited information regarding real-world therapeutic effectiveness. Objective: To compare the nature of evidence regarding the combination of approved AD treatments from RCTs versus long-term observational controlled studies (LTOCs). Methods: Comparisons of strengths, limitations, and evidence level for monotherapy [cholinesterase inhibitor (ChEI) or memantine] and combination therapy (ChEI + memantine) in RCTs versus LTOCs. Results: RCTs examined highly selected populations over months. LTOCs collected data across multiple AD stages in large populations over many years. RCTs and LTOCs show similar patterns favoring combination over monotherapy over placebo/no treatment. Long-term combination therapy compared to monotherapy reduced cognitive and functional decline and delayed time to nursing home admission. Persistent treatment was associated with slower decline. While LTOCs used control groups, adjusted for multiple covariates, had higher external validity, and favorable ethical, practical and cost considerations, their limitations included potential selection bias due to lack of placebo comparisons and randomization. Conclusions: Naturalistic LTOCs provide complementary long-term level II evidence to complement level I evidence from short-term RCTs regarding therapeutic effectiveness in AD that may otherwise be unobtainable. A coordinated strategy/consortium to pool LTOC data from multiple centers to estimate long-term comparative effectiveness, risks/benefits, and costs of AD treatments is needed. Copyright (C) 2012 S. Karger AG, Basel C1 [Atri, Alireza] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Atri, Alireza] ENRM VA Med Ctr, Ctr Geriatr Res Educ & Clin, Bedford, MA USA. [Atri, Alireza] Harvard Univ, Sch Med, Boston, MA USA. [Rountree, Susan D.; Doody, Rachelle S.] Baylor Coll Med, Dept Neurol, Alzheimers Dis & Memory Disorders Ctr, Houston, TX 77030 USA. [Lopez, Oscar L.] Univ Pittsburgh, Sch Med, Dept Neurol, Pittsburgh, PA 15261 USA. RP Atri, A (reprint author), MGH Memory Disorders Unit, 15 Parkman St,WACC 715, Boston, MA 02114 USA. EM atri@nmr.mgh.harvard.edu OI Atri, Alireza/0000-0003-4405-6973 FU NIA NIH HHS [K23 AG027171, K23AG027171, P50 AG005133, P50AG05133] NR 36 TC 10 Z9 10 U1 1 U2 10 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1660-2854 J9 NEURODEGENER DIS JI Neurodegener. Dis. PY 2012 VL 10 IS 1-4 BP 170 EP 174 DI 10.1159/000335156 PG 5 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 937LS UT WOS:000303660600035 PM 22327239 ER PT J AU McLaren, DG Sreenivasan, A Diamond, EL Mitchell, MB Van Dijk, KRA DeLuca, AN O'Brien, JL Rentz, DM Sperling, RA Atri, A AF McLaren, Donald G. Sreenivasan, Aishwarya Diamond, Eli L. Mitchell, Meghan B. Van Dijk, Koene R. A. DeLuca, Amy N. O'Brien, Jacqueline L. Rentz, Dorene M. Sperling, Reisa A. Atri, Alireza TI Tracking Cognitive Change over 24 Weeks with Longitudinal Functional Magnetic Resonance Imaging in Alzheimer's Disease SO NEURODEGENERATIVE DISEASES LA English DT Article DE Functional MRI; Clinical trial; Episodic memory; Biomarker; Dementia ID MENTAL-STATE-EXAMINATION; DEFAULT-MODE NETWORK; MEMORY IMPAIRMENT; ASSOCIATION WORKGROUPS; HIPPOCAMPAL ACTIVATION; DIAGNOSTIC GUIDELINES; CLINICAL-DIAGNOSIS; NATIONAL INSTITUTE; CEREBRAL-CORTEX; AD DEMENTIA AB Background: Previous studies have revealed that functional magnetic resonance imaging (fMRI) blood oxygen level-dependent (BOLD) signal in specific brain regions correlates with cross-sectional performance on standardized clinical trial measures in Alzheimer's disease (AD); however, the relationship between longitudinal change in fMRI-BOLD signal and neuropsychological performance remains unknown. Objective: To identify changes in regional fMRI-BOLD activity that tracks change in neuropsychological performance in mild AD dementia over 6 months. Methods: Twenty-four subjects (mean age 71.6) with mild AD dementia (mean Mini Mental State Examination 21.7, Global Clinical Dementia Rating 1.0) on stable donepezil dosing participated in two task-related fMRI sessions consisting of a face-name paired associative encoding memory paradigm 24 weeks apart during a randomized placebo-controlled pharmaco-fMRI drug study. Regression analysis was used to identify regions where the change in fMRI activity for Novel > Repeated stimulus contrast was associated with the change scores on postscan memory tests and the Free and Cued Selective Reminding Test (FCSRT). Results: Correlations between changes in postscan memory accuracy and changes in fMRI activity were observed in regions including the angular gyrus, parahippocampal gyrus, inferior frontal gyrus and cerebellum. Correlations between changes in FCSRT-free recall and changes in fMRI were observed in regions including the inferior parietal lobule, precuneus, hippocampus and parahippocampal gyrus. Conclusion: Changes in encoding-related fMRI activity in regions implicated in mnemonic networks correlated with changes in psychometric measures of episodic memory retrieval performed outside the scanner. These exploratory results support the potential of fMRI activity to track cognitive change and detect signals of short-term pharmacologic effect in early-phase AD studies. Copyright (C) 2012 S. Karger AG, Basel C1 [Atri, Alireza] Massachusetts Gen Hosp, Memory Disorders Unit, Dept Neurol, Boston, MA 02114 USA. [McLaren, Donald G.; Diamond, Eli L.; Mitchell, Meghan B.; Rentz, Dorene M.; Sperling, Reisa A.; Atri, Alireza] Harvard Univ, Sch Med, Boston, MA USA. [O'Brien, Jacqueline L.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Rentz, Dorene M.; Sperling, Reisa A.] Brigham & Womens Hosp, Dept Neurol, Ctr Alzheimer Res & Treatment, Boston, MA 02115 USA. [McLaren, Donald G.; Sreenivasan, Aishwarya; Mitchell, Meghan B.; Van Dijk, Koene R. A.; DeLuca, Amy N.; O'Brien, Jacqueline L.; Rentz, Dorene M.; Sperling, Reisa A.; Atri, Alireza] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. [McLaren, Donald G.; Sreenivasan, Aishwarya; Mitchell, Meghan B.; Atri, Alireza] ENRM VA Med Ctr, Geriatr Res Educ & Clin Ctr, Bedford, MA USA. [Van Dijk, Koene R. A.] Harvard Univ, Dept Psychol, Ctr Brain Sci, Cambridge, MA 02138 USA. RP Atri, A (reprint author), Massachusetts Gen Hosp, Memory Disorders Unit, Dept Neurol, 15 Parkman St,WACC 715, Boston, MA 02114 USA. EM atri@nmr.mgh.harvard.edu RI Van Dijk, Koene/G-3317-2012; OI Van Dijk, Koene/0000-0001-6137-4282; Atri, Alireza/0000-0003-4405-6973; McLaren, Donald/0000-0002-0566-4610 FU NIA National Institute on Aging [K23 AG027171, RO1 AG027435]; Harvard-Massachusetts Institute of Technology Health Sciences & Technology Pfizer-Merck; NIH National Institutes of Health; Forest Pharmaceuticals; Harvard Center for Neurodegeneration Repair; Clinical, Neuroimaging, and Statistics Cores of the Massachusetts Alzheimer's Disease Research Center (NIA National Institute on Aging) [P50 AG05134]; Geriatric Research, Education and Clinical Center (GRECC) at the Edith Nourse Rogers Memorial (ENRM) Veterans Administration (VA) Bedford Medical Center; Forest Research Institute; Eisai Pharmaceuticals; Forest Pharmaceuticals Inc.; H. Lundbeck A/S; Merck Co Inc.; Merz Pharmaceuticals; Novartis AG; Elan; Pfizer; Bristol-Myers-Squibb; NIH/NIA [K23, R01, P50] FX the study was supported by: NIA National Institute on Aging grants K23 AG027171 (Dr. Atri) and RO1 AG027435 (Dr. Sperling); The Harvard-Massachusetts Institute of Technology Health Sciences & Technology Pfizer-Merck Clinical Investigator Training Program (Dr. Atri); the NIH National Institutes of Health loan repayment program (Dr. Atri); Investigator-Initiated Research Grants from Forest Pharmaceuticals and The Harvard Center for Neurodegeneration & Repair; the Clinical, Neuroimaging, and Statistics Cores of the Massachusetts Alzheimer's Disease Research Center (NIA National Institute on Aging grant P50 AG05134 to Drs. Growdon and Hyman); and the Geriatric Research, Education and Clinical Center (GRECC) at the Edith Nourse Rogers Memorial (ENRM) Veterans Administration (VA) Bedford Medical Center. Less than 30% of this research was supported by an Investigator-Initiated Research Grant from Forest Research Institute. The contents of this study do not represent the views of the Department of Veterans Affairs or the United States Government.; A.A., within the past 5 years, has served as a consultant, on the advisory board, received lecture honoraria, or institutional-research grant funding from Eisai Pharmaceuticals, Forest Pharmaceuticals Inc., H. Lundbeck A/S, Merck & Co Inc., Merz Pharmaceuticals, and Novartis AG. R. A. S. has served as a consultant for Eisai Pharmaceuticals, Elan Corporation plc, Pfizer Inc., Bristol-Myers-Squibb, and Roche. She has received institutional research funding or served as a site investigator for Elan, Pfizer, Bristol-Myers-Squibb, and Forest Pharmaceuticals. Principal support for this research was provided by the NIH/NIA (K23, R01, P50 grant mechanisms). The principal author, A. A., retains full control of the data and publication rights. NR 67 TC 11 Z9 12 U1 3 U2 11 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1660-2854 J9 NEURODEGENER DIS JI Neurodegener. Dis. PY 2012 VL 9 IS 4 BP 176 EP 186 DI 10.1159/000335876 PG 11 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 940AJ UT WOS:000303862100003 PM 22456451 ER PT J AU Rodriguez, FJ Orr, BA Ligon, KL Eberhart, CG AF Rodriguez, Fausto J. Orr, Brent A. Ligon, Keith L. Eberhart, Charles G. TI Neoplastic cells are a rare component in human glioblastoma microvasculature SO ONCOTARGET LA English DT Article DE Glioblastoma; microvascular proliferation; endothelium; stem cells; FISH ID TUMOR STEM-CELLS; BEVACIZUMAB PLUS IRINOTECAN; INTEGRATED GENOMIC ANALYSIS; VASCULOGENIC MIMICRY; ENDOTHELIAL-CELLS; RECURRENT GLIOBLASTOMA; PERIVASCULAR NICHE; IDH2 MUTATIONS; BRAIN-TUMORS; GLIOMA-CELLS AB Microvascular proliferation is a key biological and diagnostic hallmark of human glioblastoma, one of the most aggressive forms of human cancer. It has recently been suggested that stem-like glioblastoma cells have the capacity to differentiate into functional endothelial cells, and that a significant proportion of the vascular lining in tumors has a neoplastic origin. In principle, this finding could significantly impact the efficacy and development of antiangiogenic therapies targeting the vasculature. While the potential of stem-like cancer cells to form endothelium in culture seems clear, in our clinical experience using a variety of molecular markers, neoplastic cells do not contribute significantly to the endothelial-lined vasculature of primary human glioblastoma. We sought to confirm this impression by analyzing vessels in glioblastoma previously examined using chromogenic in situ hybridization (CISH) for EGFR and immunohistochemistry for mutant IDH1. Vessels containing cells expressing these definitive neoplastic markers were identified in a small fraction of tumors, but only 10% of vessel profiles examined contained such cells and when identified these cells comprised less than 10% of the vascular cellularity in the cross section. Interestingly, these rare intravascular cells showing EGFR amplification by CISH or mutant IDH1 protein by immunohistochemistry were located in the middle or outer portions of vessel walls, but not amongst the morphologic boundaries of the endothelial lining. To more directly address the capacity of glioblastoma cells to contribute to the vascular endothelium, we performed double labeling (Immunofluorescence/FISH) for the endothelial marker CD34 and EGFR gene locus. Although rare CD34 positive neoplastic cells unassociated with vessels were identified (<1%), this analysis did not identify EGFR amplified cells within vascular linings, and further supports our observations that incorporation of glioblastoma cells into the tumor vessels is at best extremely rare, and therefore of questionable clinical or therapeutic significance. C1 [Rodriguez, Fausto J.; Orr, Brent A.; Eberhart, Charles G.] Johns Hopkins Univ, Dept Pathol, Baltimore, MD 21218 USA. [Ligon, Keith L.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Ligon, Keith L.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Ligon, Keith L.] Dana Farber Canc Inst, Ctr Mol Oncol Pathol, Boston, MA USA. [Ligon, Keith L.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA USA. RP Rodriguez, FJ (reprint author), Johns Hopkins Univ, Dept Pathol, Baltimore, MD 21218 USA. EM frodrig4@jhmi.edu; ceberha@jhmi.edu FU NIH [T32CA067751, 5R01NS055089] FX This work was funded by NIH postdoctoral fellowship (T32CA067751) to B.A.O and 5R01NS055089 to C.G.E. NR 71 TC 24 Z9 26 U1 0 U2 6 PU IMPACT JOURNALS LLC PI ALBANY PA 6211 TIPTON HOUSE, STE 6, ALBANY, NY 12203 USA SN 1949-2553 J9 ONCOTARGET JI Oncotarget PD JAN PY 2012 VL 3 IS 1 BP 98 EP 106 PG 9 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 940SS UT WOS:000303914000013 PM 22298889 ER PT B AU Jacoby, GA Hooper, DC AF Jacoby, George A. Hooper, David C. BE Dougherty, TJ Pucci, MJ TI Review of the Quinolone Family SO ANTIBIOTIC DISCOVERY AND DEVELOPMENT, VOLS 1 AND 2 LA English DT Article; Book Chapter ID URINARY-TRACT-INFECTION; MULTIPLE-ANTIBIOTIC-RESISTANCE; MULTIDRUG EFFLUX PUMP; ENTERICA SEROVAR TYPHIMURIUM; PELVIC-INFLAMMATORY-DISEASE; SINGLE-DOSE CIPROFLOXACIN; RANDOMIZED-CLINICAL-TRIAL; ACUTE BACTERIAL SINUSITIS; GRAM-POSITIVE BACTERIA; COLI DNA GYRASE C1 [Jacoby, George A.; Hooper, David C.] Lahey Clin Fdn, Burlington, MA 01805 USA. [Hooper, David C.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. RP Jacoby, GA (reprint author), Lahey Clin Fdn, 41 Mall Rd, Burlington, MA 01805 USA. EM george.@jacobyelahey.org; dhooper@partners.org NR 217 TC 2 Z9 3 U1 0 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 978-1-4614-1399-8 PY 2012 BP 119 EP 146 DI 10.1007/978-1-4614-1400-1_4 D2 10.1007/978-1-4614-1400-1 PG 28 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA BZX53 UT WOS:000303216800004 ER PT B AU Meyerhardt, J AF Meyerhardt, Jeffrey BE Markowitz, SD Berger, NA TI Energy Balance and Other Modifiable Host Factors on Colorectal Cancer Prognosis SO ENERGY BALANCE AND GASTROINTESTINAL CANCER SE Energy Balance and Cancer LA English DT Article; Book Chapter ID BODY-MASS INDEX; QUALITY-OF-LIFE; III COLON-CANCER; GROWTH-FACTOR-I; TREATMENT-RELATED TOXICITY; MAJOR DIETARY PATTERNS; TIME PHYSICAL-ACTIVITY; STAGE BREAST-CANCER; IOWA WOMENS HEALTH; RISK-FACTORS AB Epidemiologic and scientific research indicates that host factors that influence energy balance have a significant influence on the risk of developing colorectal cancer. Obesity and certain diets increase one's risk of developing colorectal cancer, while physical activity decreases this risk. Until recently, it was largely unknown if any of these modifiable factors influence the outcomes of patients already diagnosed with colorectal cancer. However, data are emerging of factors that may influence disease recurrences and mortality for colorectal cancer survivors. Prospective observational studies have shown that increased exercise after diagnosis and avoidance of a Western pattern diet are associated with reduced risk of cancer recurrence and improved overall survival in early stage colorectal cancer after standard therapy. Patients with class II and III obesity (BMI >= 35 kg/m(2)) have a modestly increased risk of recurrence. In contrast, change of weight after diagnosis is not associated with outcomes after diagnosis. The data supporting these observations will be reviewed and potential mechanisms of actions will be discussed. C1 [Meyerhardt, Jeffrey] Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Med Oncol, Boston, MA 02215 USA. [Meyerhardt, Jeffrey] Harvard Univ, Sch Med, Dept Med, Boston, MA 02215 USA. RP Meyerhardt, J (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Med Oncol, Boston, MA 02215 USA. EM jeffrey_meyerhardt@dfci.harvard.edu NR 117 TC 1 Z9 1 U1 2 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 978-1-4614-2366-9 J9 ENERG BALANCE CANCER JI Energy Balance Canc. PY 2012 VL 4 BP 141 EP 156 DI 10.1007/978-1-4614-2367-6_9 D2 10.1007/978-1-4614-2367-6 PG 16 WC Oncology SC Oncology GA BZW40 UT WOS:000303132900009 ER PT B AU Bertagnolli, MM AF Bertagnolli, Monica M. BE Markowitz, SD Berger, NA TI Cyclooxygenase-2 and Chronic Inflammation: Drivers of Colorectal Tumorigenesis SO ENERGY BALANCE AND GASTROINTESTINAL CANCER SE Energy Balance and Cancer LA English DT Article; Book Chapter ID FAMILIAL ADENOMATOUS POLYPOSIS; NONSTEROIDAL ANTIINFLAMMATORY DRUGS; COLON-CANCER CELLS; PHASE-II TRIAL; PROSTAGLANDIN SYNTHASE 2; PROTEIN-KINASE PATHWAYS; GROWTH-FACTOR RECEPTOR; NECROSIS-FACTOR-ALPHA; N-TERMINAL KINASE; GENE-EXPRESSION AB A common feature of the relationship between abnormal energy balance, altered hormonal regulation, and cancer is the presence of increased inflammation. In individuals with obesity-associated metabolic disorder, an increased inflammatory response can be identified on both systemic and tissue-specific levels. This chapter details the relationship between cyclooxygenase-2 (COX-2), a key mediator of local inflammatory response, and the development of colorectal cancer. It also describes the modulation of COX-2 activity as a means of preventing and treating colorectal tumors. Finally, this chapter addresses new data concerning the role of COX-2 activity in obesity and metabolic syndrome. C1 Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Surg Oncol,Dana Farber Canc Inst, Boston, MA 02115 USA. RP Bertagnolli, MM (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Surg Oncol,Dana Farber Canc Inst, Boston, MA 02115 USA. EM mbertagnolli@partners.org NR 164 TC 0 Z9 0 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 978-1-4614-2366-9 J9 ENERG BALANCE CANCER JI Energy Balance Canc. PY 2012 VL 4 BP 157 EP 182 DI 10.1007/978-1-4614-2367-6_10 D2 10.1007/978-1-4614-2367-6 PG 26 WC Oncology SC Oncology GA BZW40 UT WOS:000303132900010 ER PT B AU Kucherlapati, M Hung, K Kuraguchi, M Kucherlapati, R AF Kucherlapati, Melanie Hung, Ken Kuraguchi, Mari Kucherlapati, Raju BE Green, JE Ried, T TI Mouse Models for Colorectal Cancer SO GENETICALLY ENGINEERED MICE FOR CANCER RESEARCH: DESIGN, ANALYSIS, PATHWAYS, VALIDATION AND PRE-CLINICAL TESTING LA English DT Article; Book Chapter ID DNA MISMATCH REPAIR; FAMILIAL ADENOMATOUS POLYPOSIS; NONPOLYPOSIS COLON-CANCER; BETA-CATENIN; MICROSATELLITE INSTABILITY; APC GENE; HMLH1 PROMOTER; SOMATIC APC; INTESTINAL TUMORIGENESIS; GASTROINTESTINAL-TRACT C1 [Kucherlapati, Melanie; Kucherlapati, Raju] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Genet,Dept Med, Boston, MA 02115 USA. [Hung, Ken] Tufts Med Ctr, Dept Gastroenterol, Boston, MA 02111 USA. [Kuraguchi, Mari] Dana Farber Canc Inst, Belfer Inst Appl Canc Sci, Dept Med Oncol, Boston, MA 02115 USA. RP Kucherlapati, M (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Genet,Dept Med, Boston, MA 02115 USA. EM kucherlapati@partners.org NR 108 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 978-0-387-69803-8 PY 2012 BP 309 EP 329 DI 10.1007/978-0-387-69805-2_15 D2 10.1007/978-0-387-69805-2 PG 21 WC Oncology; Medicine, Research & Experimental SC Oncology; Research & Experimental Medicine GA BZX47 UT WOS:000303216200015 ER PT B AU Dougan, M Dranoff, G AF Dougan, Michael Dranoff, Glenn BE Wang, RF TI Immunotherapy of Cancer SO INNATE IMMUNE REGULATION AND CANCER IMMUNOTHERAPY LA English DT Article; Book Chapter ID REGULATORY T-CELLS; METASTATIC BREAST-CANCER; GROWTH-FACTOR RECEPTOR; PHASE-III TRIAL; BACILLUS-CALMETTE-GUERIN; RECOMBINANT INTERLEUKIN-2 THERAPY; HELICOBACTER-PYLORI ERADICATION; LYMPHOCYTE-ASSOCIATED ANTIGEN-4; FAMILIAL ADENOMATOUS POLYPOSIS; RANDOMIZED CONTROLLED-TRIAL C1 [Dougan, Michael; Dranoff, Glenn] Brigham & Womens Hosp, Dept Med Oncol, Boston, MA 02115 USA. [Dougan, Michael; Dranoff, Glenn] Brigham & Womens Hosp, Canc Vaccine Ctr, Dana Farber Canc Inst, Boston, MA 02115 USA. [Dougan, Michael; Dranoff, Glenn] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Dougan, Michael; Dranoff, Glenn] Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Dranoff, G (reprint author), Brigham & Womens Hosp, Dept Med Oncol, 75 Francis St, Boston, MA 02115 USA. EM glenn_dranoff@dfci.harvard.edu NR 160 TC 18 Z9 19 U1 1 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 978-1-4419-9913-9 PY 2012 BP 391 EP 414 DI 10.1007/978-1-4419-9914-6_22 D2 10.1007/978-1-4419-9914-6 PG 24 WC Oncology; Immunology SC Oncology; Immunology GA BZX39 UT WOS:000303215400022 ER PT J AU Williams, BR Sawyer, P Allman, RM AF Williams, Beverly Rosa Sawyer, Patricia Allman, Richard M. TI Wearing the Garment of Widowhood: Variations in Time Since Spousal Loss Among Community-Dwelling Older Adults SO JOURNAL OF WOMEN & AGING LA English DT Article DE widow; bereavement; older women; Black women; community-dwelling; social isolation ID SOCIAL-ISOLATION; MARITAL-STATUS; HEALTH; WOMEN; SUPPORT; LIFE; BEREAVEMENT; FAMILY; CARE; PERSPECTIVES AB We examine how the passage of time since spousal loss varies by social and demographic characteristics, using data from the University of Alabama at Birmingham Study of Aging. In multivariate analyses, African American race, female sex, lower income, and higher risk of social isolation had significant and independent associations with variation in time since spousal loss. African American women were at highest risk for long-term widowhood. Accurate characterizations of widowhood among community-dwelling older adults must consider variation in the length of time individuals are living as widowed persons and socioeconomic concomitants of long-term widowhood. C1 [Williams, Beverly Rosa] Univ Alabama Birmingham, Birmingham VA Med Ctr, Birmingham Atlanta Geriatr Res Educ & Clin Ctr, Div Gerontol Geriatr & Palliat Care,Dept Med, Birmingham, AL 35233 USA. [Williams, Beverly Rosa; Sawyer, Patricia; Allman, Richard M.] UAB Ctr Aging, Birmingham, AL USA. [Williams, Beverly Rosa; Allman, Richard M.] Birmingham Atlanta VA Geriatr Res Educ & Clin Ctr, Birmingham, AL USA. RP Williams, BR (reprint author), Univ Alabama Birmingham, Birmingham VA Med Ctr, Birmingham Atlanta Geriatr Res Educ & Clin Ctr, Div Gerontol Geriatr & Palliat Care,Dept Med, GRECC 11G,700 19th St S, Birmingham, AL 35233 USA. EM Beverly.williams3@va.gov FU NIA NIH HHS [P30AG031054, P30 AG031054, R01 AG16062, R01 AG015062]; NIDA NIH HHS [R01 DA016062] NR 48 TC 2 Z9 2 U1 0 U2 3 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 0895-2841 J9 J WOMEN AGING JI J. Women Aging PY 2012 VL 24 IS 2 BP 126 EP 139 DI 10.1080/08952841.2012.639660 PG 14 WC Gerontology; Women's Studies SC Geriatrics & Gerontology; Women's Studies GA 936FF UT WOS:000303575600004 PM 22486476 ER PT J AU Strang, BL Boulant, S Kirchhausen, T Coen, DM AF Strang, Blair L. Boulant, Steeve Kirchhausen, Tomas Coen, Donald M. TI Host Cell Nucleolin Is Required To Maintain the Architecture of Human Cytomegalovirus Replication Compartments SO MBIO LA English DT Article ID POLYMERASE SUBUNIT UL44; VIRAL-DNA REPLICATION; SIMPLEX-VIRUS TYPE-1; ACCESSORY PROTEIN UL44; CATALYTIC SUBUNIT; PROCESSIVITY FACTOR; INFECTION; BINDING; IDENTIFICATION; LOCALIZATION AB Drastic reorganization of the nucleus is a hallmark of herpesvirus replication. This reorganization includes the formation of viral replication compartments, the subnuclear structures in which the viral DNA genome is replicated. The architecture of replication compartments is poorly understood. However, recent work with human cytomegalovirus (HCMV) showed that the viral DNA polymerase subunit UL44 concentrates and viral DNA synthesis occurs at the periphery of these compartments. Any cellular factors involved in replication compartment architecture are largely unknown. Previously, we found that nucleolin, a major protein component of nucleoli, associates with HCMV UL44 in infected cells and is required for efficient viral DNA synthesis. Here, we show that nucleolin binds to purified UL44. Confocal immunofluorescence analysis demonstrated colocalization of nucleolin with UL44 at the periphery of replication compartments. Pharmacological inhibition of viral DNA synthesis prevented the formation of replication compartments but did not abrogate association of UL44 and nucleolin. Thus, association of UL44 and nucleolin is unlikely to be a nonspecific effect related to development of replication compartments. No detectable colocalization of 5-ethynyl-2'-deoxyuridine (EdU)-labeled viral DNA with nucleolin was observed, suggesting that nucleolin is not directly involved in viral DNA synthesis. Small interfering RNA (siRNA)-mediated knockdown of nucleolin caused improper localization of UL44 and a defect in EdU incorporation into viral DNA. We propose a model in which nucleolin anchors UL44 at the periphery of replication compartments to maintain their architecture and promote viral DNA synthesis. IMPORTANCE Human cytomegalovirus (HCMV) is an important human pathogen. HCMV infection causes considerable rearrangement of the structure of the nucleus, largely due to the formation of viral replication compartments within the nucleus. Within these compartments, the virus replicates its DNA genome. We previously demonstrated that nucleolin is required for efficient viral DNA synthesis and now find that the nucleolar protein nucleolin interacts with a subunit of the viral DNA polymerase, UL44, specifically at the periphery of replication compartments. Moreover, we find that nucleolin is required to properly localize UL44 at this region. Nucleolin is, therefore, involved in the organization of proteins within replication compartments. This, to our knowledge, is the first report identifying a cellular protein required for maintaining replication compartment architecture. C1 [Strang, Blair L.; Coen, Donald M.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Immune Dis Inst, Boston, MA 02115 USA. [Boulant, Steeve; Kirchhausen, Tomas] Harvard Univ, Sch Med, Dept Cell Biol, Immune Dis Inst, Boston, MA USA. Childrens Hosp, Program Cellular & Mol Med, Boston, MA 02115 USA. RP Coen, DM (reprint author), Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Immune Dis Inst, Boston, MA 02115 USA. EM don_coen@hms.harvard.edu FU Coen laboratory; NIH [AI19838, AI26077, GM 075252]; New England Regional Center of Excellence in Biodefense and Emerging Infectious Disease, Core Imaging Facility [U54 AI057159] FX We thank Lynne Chang and David Knipe (Harvard Medical School) for helpful discussions, comments on the manuscript, and provision of microscopy facilities and technical assistance in preliminary experiments. We gratefully acknowledge Les Hanakahi (University of Illinois) for providing reagents and all members of the Coen laboratory for their support, especially Jean Pesola for assistance with statistical analysis.; This work was supported by NIH grants AI19838 and AI26077 to D. M. C. and grants GM 075252 (NIH) and U54 AI057159 (New England Regional Center of Excellence in Biodefense and Emerging Infectious Disease, Core Imaging Facility) to T.K. NR 37 TC 11 Z9 12 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 2150-7511 J9 MBIO JI mBio PD JAN-FEB PY 2012 VL 3 IS 1 AR e00301-11 DI 10.1128/mBio.00301-11 PG 11 WC Microbiology SC Microbiology GA 933AK UT WOS:000303331400017 ER PT J AU Tanev, K Sablosky, M Vento, J O'Hanlon, D AF Tanev, Kaloyan Sablosky, Marylin Vento, John O'Hanlon, Donal TI Structural and functional neuroimaging methods in the diagnosis of dementias: A retrospective chart and brain imaging review SO NEUROCASE LA English DT Article DE Structural neuroimaging; Functional neuroimaging; Dementia; Alzheimer's disease ID MILD COGNITIVE IMPAIRMENT; POSITRON-EMISSION-TOMOGRAPHY; ALZHEIMERS-DISEASE; FRONTOTEMPORAL DEMENTIA; LEWY BODIES; WORK GROUP; SPECT; MRI; PET; PREDICTORS AB Objective: Assess the contribution of structural and functional neuroimaging methods to the diagnosis of dementia. Methods: This was a retrospective chart and imaging review. Participants were 24 inpatient dementia cases from a general hospital-based, university medical psychiatry unit. Data from clinical charts and imaging results were reviewed. Results: Most common initial diagnoses were dementia NOS and vascular dementia (VD); most common discharge diagnoses were VD, Alzheimer's, Dementia NOS and dementia with Lewy bodies. Most diagnostic changes occurred following family meetings or SPECT/PET, with fewer changes after CT/MRI. Conclusions: Diagnostic steps that contributed the most to the final diagnosis were the family meeting and the functional neuroimaging evaluation. C1 [Tanev, Kaloyan; Sablosky, Marylin; Vento, John; O'Hanlon, Donal] Univ Connecticut, Ctr Hlth, Dept Psychiat, Farmington, CT 06032 USA. RP Tanev, K (reprint author), Massachusetts Gen Hosp, Dept Psychiat, 55 Fruit St,Warren 1220,Blake 11, Boston, MA 02144 USA. EM ktanev@partners.org NR 31 TC 1 Z9 1 U1 2 U2 7 PU PSYCHOLOGY PRESS PI HOVE PA 27 CHURCH RD, HOVE BN3 2FA, EAST SUSSEX, ENGLAND SN 1355-4794 J9 NEUROCASE JI Neurocase PY 2012 VL 18 IS 3 BP 224 EP 234 DI 10.1080/13554794.2011.588177 PG 11 WC Clinical Neurology; Psychiatry; Psychology SC Neurosciences & Neurology; Psychiatry; Psychology GA 936BH UT WOS:000303565400006 PM 21879994 ER PT J AU Hayes, JP Morey, RA Tupler, LA AF Hayes, Jasmeet Pannu Morey, Rajendra A. Tupler, Larry A. TI A case of frontal neuropsychological and neuroimaging signs following multiple primary-blast exposure SO NEUROCASE LA English DT Article DE Blast-induced neurotrauma; Closed-head injury; Diffusion-tensor imaging; Executive control; Explosive Ordnance Disposal Service; Fractional anisotropy; Primary blast; Traumatic brain injury; White matter ID TRAUMATIC BRAIN-INJURY; POSTTRAUMATIC-STRESS-DISORDER; VERBAL-LEARNING TEST; AXONAL INJURY; PROFESSIONAL BOXERS; HEAD-INJURY; FOOTBALL PLAYERS; EXPLOSIVE BLAST; PERFORMANCE; SOLDIERS AB Blast-related traumatic brain injury (TBI) from the Afghanistan and Iraq wars represents a significant medical concern for troops and veterans. To better understand the consequences of primary-blast injury in humans, we present a case of a Marine exposed to multiple primary blasts during his 14-year military career. The neuropsychological profile of this formerly high-functioning veteran suggested primarily executive dysfunction. Diffusion-tensor imaging revealed white-matter pathology in long fiber tracks compared with a composite fractional-anisotropy template derived from a veteran reference control group without TBI. This study supports the existence of primary blast-induced neurotrauma in humans and introduces a neuroimaging technique with potential to discriminate multiple-blast TBI. C1 [Hayes, Jasmeet Pannu] VA Boston Healthcare Syst, Natl Ctr PTSD, Boston, MA 02130 USA. [Hayes, Jasmeet Pannu] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02118 USA. [Hayes, Jasmeet Pannu; Morey, Rajendra A.] Duke Univ, Duke UNC Brain Imaging & Anal Ctr, Durham, NC USA. [Hayes, Jasmeet Pannu; Morey, Rajendra A.; Tupler, Larry A.] Durham VA Med Ctr, Mental Illness Res Educ & Clin Ctr Postdeployment, Durham, NC USA. [Hayes, Jasmeet Pannu; Morey, Rajendra A.; Tupler, Larry A.] Duke Univ, Med Ctr, Dept Psychiat & Behav Sci, Durham, NC USA. RP Hayes, JP (reprint author), VA Boston Healthcare Syst, Natl Ctr PTSD 116B 2, 150 S Huntington Ave, Boston, MA 02130 USA. EM jphayes@bu.edu FU [NIMH K23 MH084013]; [K23 MH073091]; [VHA 101RX000389]; [VISN6 MIRECC] FX We would like to thank J.G. for sharing his story with us, Elizabeth Selgrade and Gregory McCarthy for helpful discussions regarding the project, and Christopher Lascola for providing a neuroradiology consult. We would also like to acknowledge the contributions of the Mid-Atlantic Mental Illness Research, Education, and Clinical Center workgroup (members include Jean C. Beckham, Patrick S. Calhoun, Rita M. Davison, A. Meade Eggleston, John A. Fairbank, Kimberly T. Green, Angela C. Kirby, Harold Kudler, Jeffrey M. Hoerle, Christine E. Marx, Scott D. Moore, Victoria Payne, Mary C. Pender, Jennifer L. Strauss, Kristy K. Straits-Troster, and Richard D. Weiner). This work was supported by grants NIMH K23 MH084013 and K23 MH073091, VHA 101RX000389, and the VISN6 MIRECC. The views expressed herein are those of the authors and do not necessarily reflect the views of the Department of Veterans Affairs. NR 65 TC 11 Z9 11 U1 3 U2 7 PU PSYCHOLOGY PRESS PI HOVE PA 27 CHURCH RD, HOVE BN3 2FA, EAST SUSSEX, ENGLAND SN 1355-4794 J9 NEUROCASE JI Neurocase PY 2012 VL 18 IS 3 BP 258 EP 269 DI 10.1080/13554794.2011.588181 PG 12 WC Clinical Neurology; Psychiatry; Psychology SC Neurosciences & Neurology; Psychiatry; Psychology GA 936BH UT WOS:000303565400009 PM 21879996 ER PT J AU Valassi, E Biller, BMK Klibanski, A Misra, M AF Valassi, Elena Biller, Beverly M. K. Klibanski, Anne Misra, Madhusmita TI Adipokines and Cardiovascular Risk in Cushing's Syndrome SO NEUROENDOCRINOLOGY LA English DT Article DE Cushing's syndrome; Adipokines; Cardiovascular risk ID NECROSIS-FACTOR-ALPHA; CORTICOTROPIN-RELEASING HORMONE; PITUITARY-ADRENAL AXIS; HUMAN ADIPOSE-TISSUE; SOLUBLE LEPTIN RECEPTOR; PLASMINOGEN-ACTIVATOR INHIBITOR-1; ANGIOTENSINOGEN GENE-EXPRESSION; VASCULAR ENDOTHELIAL-CELLS; MESSENGER-RIBONUCLEIC-ACID; MOLECULAR-WEIGHT FORM AB Cushing's syndrome (CS) is associated with increased cardiovascular morbidity and mortality. Recent evidence also suggests that increased cardiovascular risk may persist even after long-term remission of CS. Increased central obesity, a typical feature of CS, is associated with altered production of adipokines, which contributes to the pathogenesis of several metabolic and cardiovascular complications observed in this condition. In vitro and in vivo studies have shown a relationship between cortisol and adipokines in several experimental settings. In patients with either active or 'cured' CS, an increase in leptin and resistin levels as well as the release of pro-inflammatory cytokines, such as tumor necrosis factor-alpha and interleukin-6, may be associated with increased cardiovascular risk. For other adipokines, including adiponectin, results are inconclusive. Studies are needed to further elucidate the interactions between clinical and subclinical increases in cortisol production and altered adipokine release in CS. Copyright (C) 2011 S. Karger AG, Basel C1 [Misra, Madhusmita] Massachusetts Gen Hosp Children, Pediat Endocrine Unit, Boston, MA 02114 USA. [Valassi, Elena; Biller, Beverly M. K.; Klibanski, Anne; Misra, Madhusmita] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Valassi, Elena; Biller, Beverly M. K.; Klibanski, Anne] Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA 02114 USA. RP Misra, M (reprint author), Massachusetts Gen Hosp Children, Pediat Endocrine Unit, 55 Fruit St, Boston, MA 02114 USA. EM mmisra@partners.org NR 196 TC 16 Z9 18 U1 0 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0028-3835 EI 1423-0194 J9 NEUROENDOCRINOLOGY JI Neuroendocrinology PY 2012 VL 95 IS 3 BP 187 EP 206 DI 10.1159/000330416 PG 20 WC Endocrinology & Metabolism; Neurosciences SC Endocrinology & Metabolism; Neurosciences & Neurology GA 934KD UT WOS:000303442100002 PM 22057123 ER PT J AU Spencer, TJ Biederman, J Martin, JM Moorehead, TM Mirto, T Clarke, A Batchelder, H Faraone, SV AF Spencer, Thomas J. Biederman, Joseph Martin, Jessica M. Moorehead, Tara McDonnell Mirto, Tara Clarke, Allison Batchelder, Holly Faraone, Stephen V. TI Importance of Pharmacokinetic Profile and Timing of Coadministration of Short- and Long-Acting Formulations of Methylphenidate on Patterns of Subjective Responses and Abuse Potential SO POSTGRADUATE MEDICINE LA English DT Article DE stimulants; drug abuse liability; attention-deficit/hyperactivity disorder ID ORAL METHYLPHENIDATE; DOPAMINE; COCAINE; BRAIN; OCCUPANCY; RELEASE; HUMANS; SINGLE; ADHD AB Objective: Subjective responses (ie, liking, disliking) to stimulants are thought to be proxies for abuse potential. Greater subjective responses have been documented in formulations that are more rapidly absorbed. However, repeat dosing has not been examined. Methods: Subjective responses on the Drug Rating Questionnaire were compared in 26 healthy adults after administration of short- (immediate-release [IR] methylphenidate [MPH]) and long- (osmotically controlled release oral delivery system [OROS] MPH) acting stimulant formulations. The second dose was administered 4 hours after initial dosing. All subjects received all 5 conditions (ie, placebo to placebo; IR-MPH to IR-MPH; IR-MPH to OROS-MPH; OROS-MPH to IR-MPH; or OROS-MPH to OROS-MPH) in a double-blind, counter-balanced design on 5 separate days. Results: Plasma levels and subjective patterns of detection were higher when an IR formulation was administered during the ascending phase of a first-administered long-acting dose (OROS). Conclusion: These results emphasize the critical role that formulation type (IR vs OROS) and timing of administration (ascending vs descending phase) play when short- and long-acting formulations are coadministered. Such knowledge provides important information for clinicians about the safety and tolerability of the timing of repeat dosing of various permutations of coadministration of MPH formulations. C1 [Spencer, Thomas J.; Biederman, Joseph] Massachusetts Gen Hosp, Clin & Res Program Pediat Psychopharmacol, Boston, MA 02114 USA. [Spencer, Thomas J.; Biederman, Joseph] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Martin, Jessica M.; Moorehead, Tara McDonnell; Mirto, Tara; Clarke, Allison; Batchelder, Holly] Massachusetts Gen Hosp, Pediat Psychopharmacol Res Unit, Boston, MA 02114 USA. [Faraone, Stephen V.] SUNY Upstate Med Univ, Syracuse, NY USA. [Spencer, Thomas J.] Massachusetts Gen Hosp, Clin Res Program Adult ADHD, Boston, MA 02114 USA. RP Spencer, TJ (reprint author), Massachusetts Gen Hosp, Joint Program Pediat Psychopharmacol, 55 Fruit St,YAW6A, Boston, MA 02114 USA. EM tspencer@partners.org OI Faraone, Stephen/0000-0002-9217-3982 FU Janssen Scientific Affairs, LLC.; Cephalon; Eli Lilly and Company; GlaxoSmithKline; Janssen Pharmaceuticals; McNeil Pharmaceuticals; Novartis Pharmaceuticals; Pfizer Inc; National Institute of Mental Health; Shire Laboratories, Inc.; Elminda; Next Wave Pharmaceuticals; Massachusetts General Hospital (MGH) Psychiatry Academy; AstraZeneca; Fundacion Dr. Manuel Camelo A.C. in Monterrey, Mexico; Fundacion Areces (Spain); Medice Pharmaceuticals (Germany); Spanish Child Psychiatry Association; Abbott; Alza; Bristol-Myers Squibb; Celltech; Esai; Forest; Gliatech; Merck Co, Inc.; NARSAD; National Institute on Drug Abuse; New River; National Institute of Child Health and Human Development; Novartis; Noven; Neurosearch; Organon; Otsuka; Pharmacia; Prechter Foundation; Shire; Stanley Foundation; UCB Pharma, Inc.; Wyeth; National Institutes of Health (NIH); McNeil FX This article was supported by a grant to Thomas J. Spencer, MD from Janssen Scientific Affairs, LLC. The ClinicalTrials. gov identifier for the study is NCT00302458.; Thomas J. Spencer, MD has received research support from, has been a speaker or on a speakers' bureau, or has been an advisor or on an advisory board of the following: Cephalon, Eli Lilly and Company, GlaxoSmithKline, Janssen Pharmaceuticals, McNeil Pharmaceuticals, Novartis Pharmaceuticals, Pfizer Inc, the National Institute of Mental Health, Shire Laboratories, Inc., and has received royalties on adult ADHD scales (research support). Joseph Biederman, MD is currently receiving research support from the following: Elminda, Janssen Pharmaceuticals, McNeil Pharmaceuticals, Next Wave Pharmaceuticals, and Shire Laboratories, Inc. In 2011, Dr. Biederman gave an unpaid talk for Juste Pharmaceutical Spain, and received honoraria from the Massachusetts General Hospital (MGH) Psychiatry Academy for a tuition-funded CME course. He also received an honorarium from Cambridge University Press for a chapter publication. Dr. Biederman received departmental royalties from a copyrighted rating scale used for ADHD diagnoses, paid by AstraZeneca, Eli Lilly and Company, and Shire Laboratories, Inc.; these royalties are paid to the Department of Psychiatry at MGH. In 2010, Dr. Biederman received a speaker's fee from a talk given at Fundacion Dr. Manuel Camelo A.C. in Monterrey, Mexico. Dr. Biederman provided single consultations for Shionogi Pharma, Inc., and Cipher Pharmaceuticals, Inc.; the honoraria for these consultations were paid to the Department of Psychiatry at the MGH. Dr. Biederman received honoraria from the MGH Psychiatry Academy for a tuition-funded CME course. In 2009, Dr. Biederman received a speaker's fee from the following sources: Fundacion Areces (Spain), Medice Pharmaceuticals (Germany), and the Spanish Child Psychiatry Association. In previous years, Dr. Biederman received research support, consultation fees, or speaker's fees for/from the following additional sources: Abbott, Alza, AstraZeneca, Bristol-Myers Squibb, Celltech, Cephalon, Eli Lilly and Company, Esai, Forest, GlaxoSmithKline, Gliatech, Janssen Pharmaceuticals, McNeil Pharmaceuticals, Merck & Co, Inc., NARSAD, The National Institute on Drug Abuse, New River, National Institute of Child Health and Human Development, National Institute of Mental Health, Novartis, Noven, Neurosearch, Organon, Otsuka, Pfizer Inc, Pharmacia, The Prechter Foundation, Shire, The Stanley Foundation, UCB Pharma, Inc., and Wyeth. In the past year, Stephen V. Faraone, PhD received research support from Shire and the National Institutes of Health (NIH). In previous years, he received consulting fees, was on advisory boards, or participated in continuing medical education programs sponsored by: Shire, McNeil, Janssen Pharmaceuticals, Novartis, Pfizer Inc, and Eli Lilly and Company. In previous years, he received research support from Eli Lilly and Company, Shire, Pfizer Inc, and the NIH. Dr. Faraone receives royalties from a book published by Guilford Press: Straight Talk about Your Child's Mental Health. Jessica M. Martin, MA, Tara McDonnell Moorehead, BA, Tara Mirth, BA, Allison Clarke, BA, and Holly Batchelder, BS disclose no conflicts of interest. NR 20 TC 4 Z9 4 U1 0 U2 3 PU JTE MULTIMEDIA PI BERWYN PA 1235 WESTLAKES DR, STE 220, BERWYN, PA 19312 USA SN 0032-5481 J9 POSTGRAD MED JI Postgrad. Med. PD JAN PY 2012 VL 124 IS 1 BP 166 EP 173 DI 10.3810/pgm.2012.01.2529 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 934CS UT WOS:000303420200017 PM 22314126 ER PT J AU Peterson, LM Helweg-Larsen, M Volpp, KG Kimmel, SE AF Peterson, Laurel M. Helweg-Larsen, Marie Volpp, Kevin G. Kimmel, Stephen E. TI Heart attack risk perception biases among hypertension patients: The role of educational level and worry SO PSYCHOLOGY & HEALTH LA English DT Article DE comparative optimism; heart attack risk; hypertension; perceived risk; risk inaccuracy; worry ID SOCIOECONOMIC-STATUS; CARDIOVASCULAR RISK; RACIAL DISPARITIES; CANCER WORRY; HEALTH-RISK; INFORMATION; KNOWLEDGE; BEHAVIOR; SMOKERS; VACCINATION AB Risk biases such as comparative optimism (thinking one is better off than similar others) and risk inaccuracy (misestimating one's risk compared to one's calculated risk) for health outcomes are common. Little research has investigated racial or socioeconomic differences in these risk biases. Results from a survey of individuals with poorly controlled hypertension (N=813) indicated that participants showed (1) comparative optimism for heart attack risk by underestimating their heart attack risk compared to similar others, and (2) risk inaccuracy by overestimating their heart attack risk compared to their calculated heart attack risk. More highly educated participants were more comparatively optimistic because they rated their personal risk as lower; education was not related to risk inaccuracy. Neither race nor the federal poverty level was related to risk biases. Worry partially mediated the relationship between education and personal risk. Results are discussed as they relate to the existing literature on risk perception. C1 [Peterson, Laurel M.] George Washington Univ, Dept Psychol, Washington, DC 20052 USA. [Helweg-Larsen, Marie] Dickinson Coll, Dept Psychol, Carlisle, PA 17013 USA. [Volpp, Kevin G.] Philadelphia Vet Affairs Med Ctr, Leonard Davis Inst, Ctr Hlth Incent & Behav Econ, Philadelphia, PA USA. [Volpp, Kevin G.] Perelman Sch Med, Dept Med, Philadelphia, PA USA. [Volpp, Kevin G.] Univ Penn, Wharton Sch, Dept Hlth Care Management, Philadelphia, PA 19104 USA. [Kimmel, Stephen E.] Univ Penn, Dept Med, Philadelphia, PA 19104 USA. [Kimmel, Stephen E.] Univ Penn, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA. RP Peterson, LM (reprint author), George Washington Univ, Dept Psychol, Washington, DC 20052 USA. EM laurel_p@gwmail.gwu.edu NR 37 TC 4 Z9 4 U1 3 U2 6 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 0887-0446 J9 PSYCHOL HEALTH JI Psychol. Health PY 2012 VL 27 IS 6 BP 737 EP 751 DI 10.1080/08870446.2011.626856 PG 15 WC Public, Environmental & Occupational Health; Psychology, Multidisciplinary SC Public, Environmental & Occupational Health; Psychology GA 936GX UT WOS:000303580000007 PM 22148955 ER PT J AU Ristow, M AF Ristow, Michael TI Interview with Michael Ristow SO AGING-US LA English DT Editorial Material C1 Univ Jena, D-6900 Jena, Germany. [Ristow, Michael] Harvard Univ, Sch Med, Joslin Diabet Ctr, Cambridge, MA 02138 USA. [Ristow, Michael] German Inst Human Nutr, Potsdam, Germany. RP Ristow, M (reprint author), Univ Jena, D-6900 Jena, Germany. RI Ristow, Michael/O-9858-2014 OI Ristow, Michael/0000-0003-2109-2453 NR 1 TC 1 Z9 1 U1 0 U2 4 PU IMPACT JOURNALS LLC PI ALBANY PA 6211 TIPTON HOUSE, STE 6, ALBANY, NY 12203 USA SN 1945-4589 J9 AGING-US JI Aging-US PD JAN PY 2012 VL 4 IS 1 BP 2 EP 2 PG 1 WC Cell Biology SC Cell Biology GA 931SM UT WOS:000303239600002 PM 22317964 ER PT J AU Egede, LE Dismuke, C Echols, C AF Egede, Leonard E. Dismuke, Clara Echols, Carrae TI Racial/Ethnic Disparities in Mortality Risk Among US Veterans With Traumatic Brain Injury SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article ID HEALTH-CARE-SYSTEM; RACIAL DISPARITIES; ETHNIC DISPARITIES; FUNCTIONAL OUTCOMES; ADMINISTRATIVE DATA; REHABILITATION; RACE; MODERATE; COHORT AB Objectives. We examined the association of race/ethnicity with mortality risk in a national cohort of US veterans clinically diagnosed with traumatic brain injury. Methods. Between January 1, 2006 and December 31, 2006, we obtained data from a national cohort study of 7885 non-Hispanic White, 1748 Non-Hispanic Black, 314 Hispanic, and 4743 other or missing race/ethnicity veterans clinically diagnosed with traumatic brain injury in Veterans Affairs medical centers and community-based outpatient clinics. Results. Overall mortality at 48 months was 6.7% in Hispanic, 2.9% in non-Hispanic White, and 2.7% in non-Hispanic Black veterans. Compared with non-Hispanic White, Hispanic ethnicity was positively associated with a higher mortality risk (hazard ratio [HR]=2.33; 95% confidence interval [CI]=1.49, 3.64) in the race/ethnicity-only adjusted model. After adjusting for sociodemographic characteristics and comorbidities, Hispanic ethnicity continued to be positively associated (HR=1.61; 95% CI=1.00, 2.58) with a higher mortality risk relative to non-Hispanic White ethnicity. Conclusions. Hispanic ethnicity is positively associated with higher mortality risk among veterans clinically diagnosed with traumatic brain injury. More research is needed to understand the reasons for this disparity. (Am J Public Health. 2011;102:S266-S271. doi:10.2105/AJPH.2011.300176) C1 [Egede, Leonard E.; Dismuke, Clara] Med Univ S Carolina, Ctr Hlth Dispar Res, Charleston, SC 29425 USA. [Egede, Leonard E.; Dismuke, Clara; Echols, Carrae] Ralph H Johnson Vet Affairs Med Ctr, Ctr Dis Prevent & Hlth Intervent Div Populat, Charleston, SC USA. RP Egede, LE (reprint author), Med Univ S Carolina, Ctr Hlth Dispar Res, 135 Rutledge Ave,Room 280H,POB 250593, Charleston, SC 29425 USA. EM egedel@musc.edu FU Veterans Health Administration Health Services Research and Development (HSRD) [REA 08-261] FX This study was funded by the Veterans Health Administration Health Services Research and Development (HSR&D) program (grant REA 08-261). NR 34 TC 6 Z9 6 U1 1 U2 2 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 800 I STREET, NW, WASHINGTON, DC 20001-3710 USA SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PY 2012 VL 102 SU 2 BP S266 EP S271 DI 10.2105/AJPH.2011.300176 PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 928FV UT WOS:000302969500021 PM 21852658 ER PT J AU Cote, GM Hochberg, EP Muzikansky, A Hochberg, FH Drappatz, J McAfee, SL Batchelor, TT LaCasce, AS Fisher, DC Abramson, JS Armand, P Chen, YB AF Cote, Gregory M. Hochberg, Ephraim P. Muzikansky, Alona Hochberg, Fred H. Drappatz, Jan McAfee, Steven L. Batchelor, Tracy T. LaCasce, Ann S. Fisher, David C. Abramson, Jeremy S. Armand, Philippe Chen, Yi-Bin TI Autologous Stem Cell Transplantation with Thiotepa, Busulfan, and Cyclophosphamide (TBC) Conditioning in Patients with CNS Involvement by Non-Hodgkin Lymphoma SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article DE Lymphoma; Autologous stem cell transplantation; Thiotepa; CNS lymphoma; PCNSL ID CENTRAL-NERVOUS-SYSTEM; HIGH-DOSE CHEMOTHERAPY; BONE-MARROW-TRANSPLANTATION; RECURRENT PRIMARY CNS; STUDY-GROUP DSHNHL; PHASE-II; CONSOLIDATING RADIOTHERAPY; INTRAOCULAR LYMPHOMA; AGGRESSIVE LYMPHOMA; CEREBROSPINAL-FLUID AB Primary central nervous system non-Hodgkin lymphoma (PCNSL) carries a poor prognosis and, although it responds to chemotherapy, fewer than 20% of patients are long-term disease-free survivors. Secondary CNS non-Hodgkin lymphoma (SCNSL) has an even worse prognosis with a median survival of only months and very few reported long-term survivors. For both of these groups of patients, there has been interest in using high-dose chemotherapy with autologous stem cell transplantation (ASCT) following conditioning with thiotepa, busulfan, and cyclophosphamide (TBC). We performed a retrospective review (from 2006-2010) of 32 patients from the Dana-Farber Cancer Institute and Massachusetts General Hospital with PCNSL or SCNSL who underwent ASCT with TBC conditioning. Of the 32 patients, 56% received TBC/ASCT after achieving brain magnetic resonance imaging (MRI) and/or cerebrospinal fluid complete response in brain, and 44% of patients were treated with TBC/ASCT in the setting of measurable CNS disease. The 100-day transplant-related mortality rate was only 3%. The most common nonhematologic grade 3 or 4 toxicity was mucositis, which occurred in 73% of patients. Notably, there was only 1 patient with prolonged significant neurologic toxicity that manifested as ataxia and dysphagia. The 1-year OS estimate is 93% (95% confidence interval [CI]: 75%-98%), and the 1-year progression-free survival (PFS) estimate is 90% (95% CI: 72%-96%) from the date of transplantation. Although these outcomes are encouraging, longer follow-up is required and comparison with other traditional ASCT regimens used for patients with non-Hodgkin lymphoma (NHL) is warranted. Biol Blood Marrow Transplant 18: 76-83 (2012) 2012 American Society for Blood and Marrow Transplantation C1 [Cote, Gregory M.; Hochberg, Ephraim P.; Muzikansky, Alona; Hochberg, Fred H.; McAfee, Steven L.; Batchelor, Tracy T.; Abramson, Jeremy S.; Chen, Yi-Bin] MGH Canc Ctr, Boston, MA 02114 USA. [Drappatz, Jan; LaCasce, Ann S.; Fisher, David C.; Armand, Philippe] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Chen, YB (reprint author), MGH Canc Ctr, 100 Blossom St,Cox 108, Boston, MA 02114 USA. EM ychen6@partners.org OI Cote, Gregory/0000-0003-0181-886X FU Leukemia Lymphoma Society; Otsuka Pharmaceuticals, Inc. FX Dr. Chen is a recipient of a career development award in clinical research from the Leukemia Lymphoma Society, and receives funding from Otsuka Pharmaceuticals, Inc. to conduct clinical trials. The other authors have nothing to disclose. NR 27 TC 26 Z9 27 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD JAN PY 2012 VL 18 IS 1 BP 76 EP 83 DI 10.1016/j.bbmt.2011.07.006 PG 8 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 930LF UT WOS:000303140200009 PM 21749848 ER PT J AU Ruan, YC Roy, J Breton, S AF Ruan, Ye Chun Roy, Jeremy Breton, Sylvie TI REAL-TIME IN VIVO IMAGING OF ENDOCYTOSIS AND MICROVILLI EXTENSION IN EPIDIDYMAL CLEAR CELLS BY MULTIPHOTON INTRAVITAL MICROSCOPY SO JOURNAL OF ANDROLOGY LA English DT Meeting Abstract CT 37th Annual Meeting of the American-Society-of-Andrology (ASA) CY APR 21-24, 2012 CL Tucson, AZ SP Amer Soc Androl (ASA) C1 [Ruan, Ye Chun; Roy, Jeremy; Breton, Sylvie] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Program Membrane Biol,Ctr Syst Biol, Cambridge, MA 02138 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC ANDROLOGY, INC PI LAWRENCE PA C/O ALLEN PRESS, INC PO BOX 368, LAWRENCE, KS 66044 USA SN 0196-3635 J9 J ANDROL JI J. Androl. PY 2012 VL 33 IS 2 SU S BP 50 EP 51 PG 2 WC Andrology SC Endocrinology & Metabolism GA 931BG UT WOS:000303188500033 ER PT J AU Roy, J Paunescu, TG Brown, D Breton, S AF Roy, Jeremy Paunescu, Teodor G. Brown, Dennis Breton, Sylvie TI CIRCULATING ALDOSTERONE INDUCES THE APICAL ACCUMULATION OF THE PROTON PUMPING V-ATPASE IN CLEAR CELLS IN THE CAPUT EPIDIDYMIS SO JOURNAL OF ANDROLOGY LA English DT Meeting Abstract CT 37th Annual Meeting of the American-Society-of-Andrology (ASA) CY APR 21-24, 2012 CL Tucson, AZ SP Amer Soc Androl (ASA) C1 [Roy, Jeremy; Paunescu, Teodor G.; Brown, Dennis; Breton, Sylvie] Harvard Univ, Sch Med, Program Membrane Biol, Massachusetts Gen Hosp,Ctr Syst Biol, Cambridge, MA 02138 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC ANDROLOGY, INC PI LAWRENCE PA C/O ALLEN PRESS, INC PO BOX 368, LAWRENCE, KS 66044 USA SN 0196-3635 J9 J ANDROL JI J. Androl. PY 2012 VL 33 IS 2 SU S BP 71 EP 72 PG 2 WC Andrology SC Endocrinology & Metabolism GA 931BG UT WOS:000303188500087 ER PT J AU Werner, RM Norton, EC Konetzka, RT Polsky, D AF Werner, Rachel M. Norton, Edward C. Konetzka, R. Tamara Polsky, Daniel TI Do consumers respond to publicly reported quality information? Evidence from nursing homes SO JOURNAL OF HEALTH ECONOMICS LA English DT Article DE Report cards; Quality information; Nursing home care; Nursing home demand ID REPORT CARDS; MARKET SHARE; CHOICE; IMPACT AB Public reporting of quality information is designed to address information asymmetry in health care markets. Without public reporting, consumers may have little information to help them differentiate quality among providers, giving providers little incentive to compete on quality. Public reporting enables consumers to choose highly ranked providers. Using a four-year (2000-2003) panel dataset, we examine the relationship between report card scores and patient choice of nursing home after the Centers for Medicare and Medicaid Services began publicly reporting nursing home quality information on postacute care in 2002. We find that the relationship between reported quality and nursing home choice is positive and statistically significant suggesting that patients were more likely to choose facilities with higher reported post-acute care quality after public reporting was initiated. However, the magnitude of the effect was small. We conclude that there has been minimal consumer response to information in the post-acute care market. Published by Elsevier B.V. C1 [Werner, Rachel M.] Philadelphia VA Med Ctr, Philadelphia, PA 19104 USA. [Werner, Rachel M.; Polsky, Daniel] Univ Penn, Philadelphia, PA 19104 USA. [Norton, Edward C.] Univ Michigan, Ann Arbor, MI 48109 USA. [Konetzka, R. Tamara] Univ Chicago, Chicago, IL 60637 USA. RP Werner, RM (reprint author), Philadelphia VA Med Ctr, 1230 Blockley Hall,423 Guardian Dr, Philadelphia, PA 19104 USA. EM rwerner@upenn.edu; ecnorton@umich.edu; konetzka@uchicago.edu; polsky@mail.med.upenn.edu OI , Edward/0000-0003-4555-0631 FU Agency for Healthcare Research and Quality [R01 HS016478-01]; VA HSR&D Career Development Award FX This research was funded by a grant from the Agency for Healthcare Research and Quality (R01 HS016478-01). Rachel Werner is funded in part by a VA HSR&D Career Development Award. The authors thank Ying Fan, David Grabowski, and Alan Zaslavsky for helpful comments on an earlier draft of this manuscript, and seminar participants at Imperial College London, Harvard Health Care Policy, University of South Florida, University of Miami at Ohio, and the University of Michigan. NR 28 TC 32 Z9 32 U1 1 U2 21 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-6296 EI 1879-1646 J9 J HEALTH ECON JI J. Health Econ. PD JAN PY 2012 VL 31 IS 1 BP 50 EP 61 DI 10.1016/j.jhealeco.2012.01.001 PG 12 WC Economics; Health Care Sciences & Services; Health Policy & Services SC Business & Economics; Health Care Sciences & Services GA 928GW UT WOS:000302972200005 PM 22307033 ER PT J AU Murray, DR Mummidi, S Valente, AJ Yoshida, T Somanna, NK Delafontaine, P Dinarello, CA Chandrasekar, B AF Murray, David R. Mummidi, Srinivas Valente, Anthony J. Yoshida, Tadashi Somanna, Naveen K. Delafontaine, Patrice Dinarello, Charles A. Chandrasekar, Bysani TI beta 2 adrenergic activation induces the expression of IL-18 binding protein, a potent inhibitor of isoproterenol induced cardiomyocyte hypertrophy in vitro and myocardial hypertrophy in vivo SO JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY LA English DT Article DE Signal transduction; Transcription; Cloning; Molecular mechanism; Adrenergic stimulation; Heart failure ID NF-KAPPA-B; NATRIURETIC-PEPTIDE GENE; HEART-FAILURE; BETA(2)-ADRENERGIC RECEPTOR; INFLAMMATORY CYTOKINES; TRANSCRIPTION FACTORS; CARDIAC-HYPERTROPHY; PRESSURE-OVERLOAD; RESPONSE ELEMENT; FAILING HEART AB Both the sympathetic nervous system and the proinflammatory cytokine interleukin-18 (IL-18) play key roles in the pathophysiology of the hypertrophied failing heart IL-18 binding protein (IL-18BP), a natural inhibitor of IL-18, counters its biological effects. beta-AR stimulation induces IL-18 expression, but whether it also regulates IL-18BP is not known. Here we demonstrate that the beta-AR agonist isoproterenol (ISO) increases steady state IL-18BP mRNA and protein levels in adult mouse cardiomyocytes in a beta(2)-AR-dependent manner. We cloned mouse Il18bp 5'cis-regulatory region, and identified putative CREB and C/EBP beta transcription factor-binding sites. Forced expression of mutant CREB or C/EBP beta knockdown markedly attenuated ISO-induced Il18bp transcription and deletion or mutation of CREB and C/EBP motifs in the Il18bp promoter reduced ISO-induced promoter-reporter gene activity. ISO induced CREB and C/EBI beta activation in cardiomyocytes via PI3K/Akt and ERK1/2. Importantly, ISO-induced hypertrophy in vitro was dependent on IL-18 induction as it was blunted by IL-18 neutralizing antibodies and forced expression of IL-18BP. Moreover, ISO-induced hypertrophy was markedly attenuated in IL-18 null and IL-18BP transgenic mice. These data support the novel concept that beta-AR activation, in addition to inducing cardiomyocyte hypertrophy via IL-18, concomitantly induces a countering effect by stimulating IL-18BP expression, and that ISO-induced cardiomyocyte hypertrophy may result from a net effect of IL-18 and IL-18BP induction. (C) 2011 Elsevier Ltd. All rights reserved. C1 [Yoshida, Tadashi; Delafontaine, Patrice; Chandrasekar, Bysani] Tulane Univ, Sch Med, Inst Heart & Vasc, New Orleans, LA 70112 USA. [Murray, David R.] William S Middleton Mem Vet Adm Med Ctr, Madison, WI 53705 USA. [Mummidi, Srinivas; Valente, Anthony J.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Somanna, Naveen K.] Tulane Univ, Sch Med, New Orleans, LA 70112 USA. [Dinarello, Charles A.] Univ Colorado, Dept Med, Aurora, CO USA. [Chandrasekar, Bysani] SE Louisiana Vet Hlth Care Syst, Res Serv, New Orleans, LA 70161 USA. RP Chandrasekar, B (reprint author), Tulane Univ, Sch Med, Inst Heart & Vasc, 1430 Tulane Ave,SL-48, New Orleans, LA 70112 USA. EM bchandra@tulane.edu RI Mummidi, Srinivas/C-1004-2008 OI Mummidi, Srinivas/0000-0002-4068-6380 FU Veterans Affairs Office of Research and Development- Biomedical Laboratory Research and Development Service [1IO1BX000246]; NHLBI [HL-86787]; [I01BX007080]; [AI043279]; [HL-70241]; [HL-80682]; [AI15614] FX This work was supported by the Veterans Affairs Office of Research and Development- Biomedical Laboratory Research and Development Service Award 1IO1BX000246 and the NHLBI Grant HL-86787 (to BC). SM is supported by I01BX007080 and AI043279. PD is a supported by HL-70241 and HL-80682. CAD is supported by AI15614. The contents of this report do not represent the views of the Department of Veterans Affairs or the United States Government. NR 43 TC 14 Z9 17 U1 0 U2 7 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2828 EI 1095-8584 J9 J MOL CELL CARDIOL JI J. Mol. Cell. Cardiol. PD JAN PY 2012 VL 52 IS 1 BP 206 EP 218 DI 10.1016/j.yjmcc.2011.09.022 PG 13 WC Cardiac & Cardiovascular Systems; Cell Biology SC Cardiovascular System & Cardiology; Cell Biology GA 932FE UT WOS:000303275000024 PM 22004899 ER PT S AU Stylianopoulos, T Wong, C Bawendi, MG Jain, RK Fukumura, D AF Stylianopoulos, Triantafyllos Wong, Cliff Bawendi, Moungi G. Jain, Rakesh K. Fukumura, Dai BE Duzgunes, N TI MULTISTAGE NANOPARTICLES FOR IMPROVED DELIVERY INTO TUMOR TISSUE SO NANOMEDICINE: CANCER, DIABETES, AND CARDIOVASCULAR, CENTRAL NERVOUS SYSTEM, PULMONARY AND INFLAMMATORY DISEASES SE Methods in Enzymology LA English DT Review; Book Chapter ID MESOPOROUS SILICON PARTICLES; IN-VIVO; INTERSTITIAL HYPERTENSION; THERAPEUTIC APPLICATIONS; EXTRACELLULAR-MATRIX; SOLID TUMORS; SUBCUTANEOUS TUMORS; FIBRILLAR COLLAGEN; NEOPLASTIC TISSUES; GENE-EXPRESSION AB The enhanced permeability and retention (EPR) effect has been a key rationale for the development of nanoscale carriers to solid tumors. As a consequence of EPR, nanotherapeutics are expected to improve drug and detection probe delivery, have less adverse effects than conventional chemotherapy, and thus result in improved detection and treatment of tumors. Physiological barriers posed by the abnormal tumor microenvironment, however, can hinder the homogeneous delivery of nanomedicine in amounts sufficient to eradicate cancer. To effectively enhance the therapeutic outcome of cancer patients by nanotherapeutics, we have to find ways to overcome these barriers. One possibility is to exploit the abnormal tumor microenvironment for selective and improved delivery of therapeutic agents to tumors. Recently, we proposed a multistage nanoparticle delivery system as a potential means to enable uniform delivery throughout the tumor and improve the efficacy of anticancer therapy. Here, we describe the synthesis of a novel multistage nanoparticle formulation that shrinks in size once it enters the tumor interstitial space to optimize the delivery to tumors as well as within tumors. Finally, we provide detailed experimental methods for the characterization of such nanoparticles. C1 [Stylianopoulos, Triantafyllos] Univ Cyprus, Dept Mech & Mfg Engn, Nicosia, Cyprus. [Wong, Cliff; Bawendi, Moungi G.] MIT, Dept Chem, Cambridge, MA 02139 USA. [Jain, Rakesh K.; Fukumura, Dai] Harvard Univ, Sch Med, Boston, MA USA. [Jain, Rakesh K.; Fukumura, Dai] Massachusetts Gen Hosp, Edwin L Steele Lab, Boston, MA 02114 USA. RP Stylianopoulos, T (reprint author), Univ Cyprus, Dept Mech & Mfg Engn, Nicosia, Cyprus. OI Stylianopoulos, Triantafyllos/0000-0002-3093-1696 FU NCI NIH HHS [R01-CA096915, P01 CA080124, P01-CA080124, R01 CA096915, R01 CA126642, R01-CA126642]; NCRR NIH HHS [S10 RR027070, S10-RR027070] NR 70 TC 21 Z9 21 U1 4 U2 33 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0076-6879 BN 978-0-12-391860-4 J9 METHOD ENZYMOL JI Methods Enzymol. PY 2012 VL 508 BP 109 EP 130 DI 10.1016/B978-0-12-391860-4.00006-9 PG 22 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BZW43 UT WOS:000303133200006 PM 22449923 ER PT S AU Erdem, SS Sazonova, IY Hara, T Jaffer, FA McCarthy, JR AF Erdem, S. Sibel Sazonova, Irina Y. Hara, Tetsuya Jaffer, Farouc A. McCarthy, Jason R. BE Duzgunes, N TI DETECTION AND TREATMENT OF INTRAVASCULAR THROMBI WITH MAGNETOFLUORESCENT NANOPARTICLES SO NANOMEDICINE: CANCER, DIABETES, AND CARDIOVASCULAR, CENTRAL NERVOUS SYSTEM, PULMONARY AND INFLAMMATORY DISEASES SE Methods in Enzymology LA English DT Review; Book Chapter ID ACUTE MYOCARDIAL-INFARCTION; ACUTE ISCHEMIC-STROKE; IN-VIVO; TARGETED THROMBOLYSIS; CONTRAST AGENT; IRON-OXIDE; FIBRIN; ACCUMULATION; PLATELETS; PEPTIDE AB Thrombosis, the formation of a clot within a blood vessel, underlies a number of life-threatening cardiovascular disorders such as heart attack, ischemic stroke, pulmonary embolism, and deep vein thrombosis. These conditions affect the lives of millions of people worldwide and result in significant morbidity and mortality. It is thus crucial to develop novel methodologies to enhance the detection and treatment of these disorders. Thrombolysis, or the dissolution of blood clots, relies upon the administration of exogenous plasminogen activators (PAs) that lyse fibrin. Yet, there are several drawbacks to the use of current PAs, including significant risks of uncontrolled bleeding and suboptimal efficacy and pharmacokinetics. Nanomaterials are well positioned to address these priority issues in thrombolysis, via the alteration of PA pharmacokinetics and biodistribution. Additionally, due to the multifunctional nature of nanoparticles, these thrombolytics may be targeted to the site of occlusion, effectively concentrating the drug where it is most needed. Herein, we describe the methodology associated with the synthesis of a novel thrombus-targeted fibrinolytic nanoagent. At each step of the synthesis, we analyze the nanomaterials, including their physical properties and their ability to bind to thrombosis targets of interest. The effect of the conjugation of tPA to the nanoparticle surface on the amidolytic and fibrinolytic activities of nanoagents is also investigated. Lastly, the in vivo binding of the targeted thrombolytic to intravascular thrombi is examined. C1 [Erdem, S. Sibel; McCarthy, Jason R.] Harvard Univ, Sch Med, Ctr Syst Biol, Charlestown, MA USA. [Erdem, S. Sibel; McCarthy, Jason R.] Massachusetts Gen Hosp, Charlestown, MA USA. [Sazonova, Irina Y.] Georgia Hlth Sci Univ, Cardiol Sect, Dept Med, Med Coll Georgia, Augusta, GA USA. [Hara, Tetsuya; Jaffer, Farouc A.] Harvard Univ, Sch Med, Div Cardiol, Cardiovasc Res Ctr, Boston, MA USA. [Hara, Tetsuya; Jaffer, Farouc A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Erdem, SS (reprint author), Harvard Univ, Sch Med, Ctr Syst Biol, Charlestown, MA USA. OI Jaffer, Farouc/0000-0001-7980-384X NR 23 TC 5 Z9 5 U1 1 U2 17 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0076-6879 BN 978-0-12-391860-4 J9 METHOD ENZYMOL JI Methods Enzymol. PY 2012 VL 508 BP 191 EP 209 DI 10.1016/B978-0-12-391860-4.00010-0 PG 19 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BZW43 UT WOS:000303133200010 PM 22449927 ER PT J AU Kim, SW Maturo, S Dwyer, D Monash, B Yager, PH Zanger, K Hartnick, CJ AF Kim, Sang W. Maturo, Stephen Dwyer, Danielle Monash, Bradley Yager, Phoebe H. Zanger, Kerstin Hartnick, Christopher J. TI Interdisciplinary Development and Implementation of Communication Checklist for Postoperative Management of Pediatric Airway Patients SO OTOLARYNGOLOGY-HEAD AND NECK SURGERY LA English DT Article DE safety; quality; checklist; pediatric airway; pediatric surgery ID INFORMATION-TRANSFER; INTENSIVE-CARE; SURGERY AB Objective. The authors describe their multidisciplinary experience in applying the Institute of Health Improvement methodology to develop a protocol and checklist to reduce communication error during transfer of care for postoperative pediatric surgical airway patients. Preliminary outcome data following implementation of the protocol and checklist are also presented. Study Design. Prospective study from July 1, 2009, to February 1, 2011. Setting. Tertiary care center. Subjects. One hundred twenty-six pediatric airway patients who required coordinated care between Massachusetts Eye and Ear Infirmary and Massachusetts General Hospital. Methods. Two sentinel events involving airway emergencies demonstrated a critical need for a standardized, comprehensive instrument that would ensure safe transfer of care. After development and implementation of the protocol and checklist, an initial pilot period on the first set of 9 pediatric airway patients was reassessed. Subsequent prospective 11-month follow-up data of 93 pediatric airway patients were collected and analyzed. Results. A multidisciplinary pediatric team developed and implemented a formalized, postoperative checklist and transfer protocol. After implementation of the checklist and transfer protocol, prospective analysis showed no adverse events from miscommunication during transfer of care over the subsequent 11-month period involving 93 pediatric airway patients. Conclusion. There has been very little written in the quality and safety patient literature about coordinating effective transfer of care between the pediatric surgical and medical subspecialty realms. After design and implementation of a simple, electronically based transfer-of-care checklist and protocol, the number of postsurgical pediatric airway information transfer and communication errors decreased significantly. C1 [Kim, Sang W.; Maturo, Stephen; Hartnick, Christopher J.] Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02104 USA. [Dwyer, Danielle; Monash, Bradley; Yager, Phoebe H.; Zanger, Kerstin] Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA. RP Hartnick, CJ (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol, 243 Charles St, Boston, MA 02104 USA. EM christopher_hartnick@meei.harvard.edu NR 11 TC 13 Z9 13 U1 0 U2 2 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 0194-5998 J9 OTOLARYNG HEAD NECK JI Otolaryngol. Head Neck Surg. PD JAN PY 2012 VL 146 IS 1 BP 129 EP 134 DI 10.1177/0194599811421745 PG 6 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA 935SA UT WOS:000303539300023 PM 21908802 ER PT S AU Applegate, MB Hariri, LP Beagle, J Tan, KM Chee, C Hales, CA Suter, MJ AF Applegate, Matthew B. Hariri, Lida P. Beagle, John Tan, Khay Ming Chee, Chunmin Hales, Charles A. Suter, Melissa J. BE Kollias, N Choi, B Zeng, H Kang, HW Knudsen, BE Wong, BJF Ilgner, JF Izdebski, K Suter, MJ Lam, S Brenner, M Gregory, KW Tearney, GJ Marcu, L Hirschberg, H Madsen, S MahadevanJansen, A Jansen, ED Mandelis, A TI Assessment of smoke inhalation injury using volumetric optical frequency domain imaging in sheep models SO PHOTONIC THERAPEUTICS AND DIAGNOSTICS VIII, PTS 1 AND 2 SE Proceedings of SPIE LA English DT Proceedings Paper CT Conference on Photonic Therapeutics and Diagnostics VIII CY JAN 21-24, 2012 CL San Francisco, CA SP SPIE DE Smoke; Optical Frequency Domain Imaging; Inhalation injury; Optical Coherence Tomography ID IN-VIVO AB Smoke inhalation injury is a serious threat to victims of fires and explosions, however accurate diagnosis of patients remains problematic. Current evaluation techniques are highly subjective, often involving the integration of clinical findings with bronchoscopic assessment. It is apparent that new quantitative methods for evaluating the airways of patients at risk of inhalation injury are needed. Optical frequency domain imaging (OFDI) is a high resolution optical imaging modality that enables volumetric microscopy of the trachea and upper airways in vivo. We anticipate that OFDI may be a useful tool in accurately assessing the airways of patients at risk of smoke inhalation injury by detecting injury prior to the onset of symptoms, and therefore guiding patient management. To demonstrate the potential of OFDI for evaluating smoke inhalation injury, we conducted a preclinical study in which we imaged the trachea/upper airways of 4 sheep prior to, and up to 60 minutes post exposure to cooled cotton smoke. OFDI enabled the visualization of increased mucus accumulation, mucosal thickening, epithelial disruption and sloughing, and increased submucosal signal intensity attributed to polymorphonuclear infiltrates. These results were consistent with histopathology findings. Bronchoscopic inspection of the upper airways appeared relatively normal with only mild accumulation of mucus visible within the airway lumen. The ability of OFDI to not only accurately detect smoke inhalation injury, but to quantitatively assess and monitor the progression or healing of the injury over time may provide new insights into the management of patients such as guiding clinical decisions regarding the need for intubation and ventilator support. C1 [Applegate, Matthew B.; Beagle, John; Tan, Khay Ming; Chee, Chunmin; Hales, Charles A.; Suter, Melissa J.] Massachusetts Gen Hosp, Pulm & Crit Care Unit, Boston, MA 02114 USA. RP Applegate, MB (reprint author), Massachusetts Gen Hosp, Pulm & Crit Care Unit, Boston, MA 02114 USA. NR 14 TC 0 Z9 0 U1 0 U2 2 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-0-8194-8850-3 J9 PROC SPIE PY 2012 VL 8207 AR 82073N DI 10.1117/12.909363 PG 6 WC Optics; Radiology, Nuclear Medicine & Medical Imaging SC Optics; Radiology, Nuclear Medicine & Medical Imaging GA BZR49 UT WOS:000302580900069 ER PT J AU Smits, JAJ Minhajuddin, A Thase, ME Jarrett, RB AF Smits, Jasper A. J. Minhajuddin, Abu Thase, Michael E. Jarrett, Robin B. TI Outcomes of Acute Phase Cognitive Therapy in Outpatients with Anxious versus Nonanxious Depression SO PSYCHOTHERAPY AND PSYCHOSOMATICS LA English DT Article DE Cognitive therapy; Major depressive disorder; Anxious depression; Treatment outcome ID STAR-ASTERISK-D; RECURRENT DEPRESSION; MAJOR DEPRESSION; CONTINUATION PHASE; BEHAVIOR-THERAPY; ANXIETY SYMPTOMS; SOCIAL PHOBIA; DISORDER; FLUOXETINE; RELAPSE AB Objective: Compared to nonanxious depressed patients, anxious depressed patients respond less to pharmacotherapy, prompting consideration of alternate treatments. Based on the transdiagnostic principles of cognitive therapy (CT), we predicted that anxious depressed patients would respond as well to CT as nonanxious depressed patients. Method: Adults (n = 523) with recurrent major depressive disorder received 12-14 weeks of CT as part of the Continuation Phase Cognitive Therapy Relapse Prevention Trial. Anxious depressed patients (n = 264; 50.4%) were compared to nonanxious depressed patients (n = 259; 49.6%) on demographic variables, initial severity, attrition, and rates and patterns of response and remission. Results: Anxious depressed patients presented with greater illness severity and had significantly lower response (55.3 vs. 68.3%) and remission rates (26.9 vs. 40.2%) based on clinician-administered measures. By contrast, smaller between-group differences for attrition, and for response (59.1 vs. 64.9%) and remission (41.7 vs. 48.7%) rates on self-report measures were not significant. Further, anxious depressed patients had greater speed of improvement on self-reported anxiety symptom severity and clinician-rated depressive and anxiety symptom severity measures. Conclusion: Consistent with prior reports, anxious depressed patients presented with greater severity and, following CT, had lower response and remission rates on clinician-administered scales. However, anxious depressed patients improved more rapidly and response and remission rates on self-report measures were not significantly different from nonanxious depressed patients. Our findings suggest that anxious depressed patients may simply need additional time or more CT sessions to reach outcomes fully comparable to those of less anxious patients. Copyright (C) 2012 S. Karger AG, Basel C1 [Smits, Jasper A. J.] So Methodist Univ, Dept Psychol, Dedman Coll, Dallas, TX 75275 USA. [Minhajuddin, Abu; Jarrett, Robin B.] Univ Texas SW Med Ctr Dallas, Dept Psychiat, Dallas, TX 75390 USA. [Thase, Michael E.] Univ Penn, Sch Med, Philadelphia, PA 19104 USA. [Thase, Michael E.] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. [Thase, Michael E.] Univ Pittsburgh, Med Ctr, Pittsburgh, PA USA. RP Smits, JAJ (reprint author), So Methodist Univ, Dept Psychol, Dedman Coll, POB 750442, Dallas, TX 75275 USA. EM jsmits@smu.edu RI Smits, Jasper/A-4350-2008; OI Smits, Jasper/0000-0001-7128-9807; Smits, Jasper/0000-0003-1633-9693 FU National Institute of Mental Health (NIMH) [K24MH001571, R01MH058397, R0IMH069619, R01MH058356, R01MH069618]; Eli Lilly Co.; CT; Forest; GlaxoSmithKline; Otsuka; Rexahn; Agency for Healthcare Research and Quality; American Psychiatric Publishing Inc.; Guilford Publications; Herald House; W.W. Norton Co. Inc.; National Institutes of Health [R01MH075889, R01DA027533]; Oxford University Press; Merck FX This report was supported by Grants No. K24MH001571, R01MH058397 and R0IMH069619 (to Robin B. Jarrett, PhD) and R01MH058356 and R01MH069618 (to Michael E. Thase, MD) from the National Institute of Mental Health (NIMH).; We appreciate the support of the NIMH. We wish to acknowledge the unrestricted support of Eli Lilly & Co., who provided the fluoxetine and matched pill placebo for use in the continuation phase of this research until 2006. Thereafter, study materials were purchased and prepared to appear identical for both sites by the pharmacy at the University of Texas Southwestern Medical Center at Dallas.; Dr. Smits is currently supported by the National Institutes of Health Grants No. R01MH075889 and R01DA027533 and receives royalties from Oxford University Press. During the past 3 years, he has received grant support from Organon/Schering-Plough (now Merck).; Dr. Thase has served as a consultant to and was a member of various advisory boards for Eli Lilly & Co. and received honoraria for talks sponsored by this company. In addition to Eli Lilly & Co., during the past 3 years Dr. Thase has consulted with, served on advisory boards for or received honoraria for talks from: Aldolor, Alkermes, AstraZeneca, Bristol-Myers Squibb, Dey, Forest Laboratories, GlaxoSmithKline, Janssen Pharmaceutica, Lundbeck, MedAvante Inc., Merck, Neuronetics Inc., Otsuka, Pam Lab, Pfizer Pharmaceuticals, PGx (now Forest), PharmaNeuroboost, Rexahn, Schering-Plough, Shire US Inc., Supernus Pharmaceuticals, Transcept Pharmaceuticals, and Wyeth Pharmaceuticals (now Pfizer). During the past 2 years, he has received grant support from Eli Lilly & Co., Forest, GlaxoSmithKline, Otsuka, and Rexahn, in addition to funding from the National Institutes of Mental Health and the Agency for Healthcare Research and Quality. He has equity holdings in MedAvante Inc. and has received royalties from American Psychiatric Publishing Inc., Guilford Publications, Herald House, and W.W. Norton & Co. Inc. One book currently promoted by American Psychiatric Publishing Inc. specifically pertains to CT. Dr. Thase also discloses that his spouse is an employee of Embryon Inc. (formerly Advogent and Cardinal Health), which does business with several pharmaceutical companies that market medications used to treat depression.; Dr. Jarrett's medical center receives fees from the CT she provides to patients. Dr. Jarrett is a paid consultant to the NIMH. NR 30 TC 14 Z9 14 U1 2 U2 5 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0033-3190 J9 PSYCHOTHER PSYCHOSOM JI Psychother. Psychosom. PY 2012 VL 81 IS 3 BP 153 EP 160 DI 10.1159/000334909 PG 8 WC Psychiatry; Psychology SC Psychiatry; Psychology GA 929SY UT WOS:000303087200003 PM 22398963 ER PT J AU Kutner, NG Zhang, R Huang, YJ Johansen, KL AF Kutner, Nancy G. Zhang, Rebecca Huang, Yijian Johansen, Kirsten L. TI Impact of Race on Predialysis Discussions and Kidney Transplant Preemptive Wait-Listing SO AMERICAN JOURNAL OF NEPHROLOGY LA English DT Article DE Education; Kidney transplantation; Preemptive wait-listing; Race; United States Renal Data System ID RENAL-TRANSPLANTATION; PATIENT EDUCATION; ACCESS; DIALYSIS; DISPARITIES AB Background/Aims: US registry data have consistently shown that blacks are less likely than whites to be wait-listed before beginning dialysis. Methods: The Comprehensive Dialysis Study (CDS) was a special study conducted by the US Renal Data System (USRDS) in which a national cohort of patients who began maintenance dialysis therapy in 2005-2007 were asked whether kidney transplantation (KT) had been discussed with them before they started dialysis. Using responses from black and white CDS participants and information from the USRDS, we investigated preemptive wait-listing as a function of patient-reported predialysis KT discussion. Results: Among those reporting early KT discussion, 31.0% of patients preemptively wait-listed were black, compared to 27.5% of those not preemptively wait-listed. Two thirds of preemptively wait-listed patients had received nephrology care more than 12 months before starting dialysis and reported that KT was discussed with them 12 months or more before dialysis. Early KT discussion and higher serum albumin and hemoglobin levels remained significant predictors of preemptive wait-listing in an adjusted logistic regression analysis. Among those preemptively wait-listed, 33% of blacks and 60% of whites had received a transplant by September 30, 2009 (study end date). Conclusion: Early KT discussion appeared to reduce barriers to black patients' waiting list placement before the start of dialysis, which in turn may facilitate earlier access to a deceased donor organ transplant. Copyright (C) 2012 S. Karger AG, Basel C1 [Kutner, Nancy G.] Emory Univ, Dept Rehabil Med, Rehabil Qual Life Special Studies Ctr, US Renal Data Syst, Atlanta, GA 30322 USA. [Johansen, Kirsten L.] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. [Johansen, Kirsten L.] San Francisco VA Med Ctr, Nephrol Sect, San Francisco, CA USA. RP Kutner, NG (reprint author), Emory Univ, Dept Rehabil Med, Rehabil Qual Life Special Studies Ctr, US Renal Data Syst, Atlanta, GA 30322 USA. EM nkutner@emory.edu FU National Institutes of Health [HHSN267200715004C, N01-DK-7-5004] FX This study was supported by contract HHSN267200715004C, ADB No. N01-DK-7-5004 (N.G.K.), from the National Institutes of Health. NR 20 TC 12 Z9 12 U1 6 U2 7 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0250-8095 J9 AM J NEPHROL JI Am. J. Nephrol. PY 2012 VL 35 IS 4 BP 305 EP 311 DI 10.1159/000336891 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA 927HB UT WOS:000302896900001 PM 22414927 ER PT J AU Li, YM Shlipak, MG Grunfeld, C Choi, AI AF Li, Yongmei Shlipak, Michael G. Grunfeld, Carl Choi, Andy I. TI Incidence and Risk Factors for Acute Kidney Injury in HIV Infection SO AMERICAN JOURNAL OF NEPHROLOGY LA English DT Article DE Acute kidney injury; HIV; Chronic kidney disease; Proteinuria; Hypoalbuminemia ID ACUTE-RENAL-FAILURE; HUMAN-IMMUNODEFICIENCY-VIRUS; DISEASE; ASSOCIATION; SURVIVAL AB Background/Aims: Although HIV-infected persons are at higher risk for acute kidney injury (AKI) during hospitalization compared with their uninfected counterparts, risk factors for AKI are not well-defined. We aimed to describe the evolving incidence of AKI among HIV-infected individuals and to identify important AKI risk factors. Methods: We conducted a prospective cohort study of 56,823 HIV-infected persons in the Department of Veterans Affairs Clinical Case Registry. Outcomes were: AKI (acute in-hospital serum creatinine increase of >= 0.3 mg/dl, or a relative increase by 50% or greater), and dialysis-requiring AKI. We used proportional hazards regressions to identify risk factors. Results: From its peak in 1995 at 62 per 1,000 person-years, the incidence of AKI declined after the introduction of highly active antiretroviral therapy (HAART) in 1996 to a low point of 25 per 1,000 person-years in 2006. Incidence of dialysis-requiring AKI declined in the early 1990s, but doubled between 2000 and 2006. Using multivariate proportional hazard regression, we identified the following strong risk factors for AKI: chronic kidney disease (eGFR <60 ml/min/1.73 m(2)) (5.38, 95% CI: 5.11-5.67), proteinuria (1.78, 1.70-1.87), low serum albumin (<3.7 mg/dl) (5.24, 4.82-5.71), low body mass index (<18.5 kg/m(2)) (1.69, 1.54-1.86), cardiovascular disease (1.77, 1.66-1.89), low CD4 count (<200 cells/mm(3)) (2.54, 2.33-2.77), and high viral load (>= 100,000 copies/ml) (2.51, 2.28-2.75). In addition, there was substantial heterogeneity in the strengths of risk factors for dialysis-requiring AKI before and after the introduction of HAART. Conclusions: Although AKI incidence has decreased during the HAART era, it remains common in HIV-infected persons and appears attributable to both kidney-and HIV-related factors. Copyright (C) 2012 S. Karger AG, Basel C1 [Li, Yongmei; Shlipak, Michael G.; Grunfeld, Carl; Choi, Andy I.] San Francisco VA Med Ctr, Dept Med, San Francisco, CA USA. [Shlipak, Michael G.; Choi, Andy I.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. RP Shlipak, MG (reprint author), San Francisco VA Med Ctr, 4150 Clement St,Box 111A1, San Francisco, CA 94121 USA. EM michael.shlipak@ucsf.edu FU National Institutes of Health [K23DK080645-01A1, K23AI65244, R01 DK066488-01, 1R03AG034871-01] FX This study was supported by grants from the National Institutes of Health (K23DK080645-01A1, K23AI65244, R01 DK066488-01, 1R03AG034871-01). These funding sources had no involvement in the design or execution of this study. NR 28 TC 9 Z9 9 U1 1 U2 4 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0250-8095 J9 AM J NEPHROL JI Am. J. Nephrol. PY 2012 VL 35 IS 4 BP 327 EP 334 DI 10.1159/000337151 PG 8 WC Urology & Nephrology SC Urology & Nephrology GA 927HB UT WOS:000302896900004 PM 22456100 ER PT S AU Ackerman, ME Dugast, AS Alter, G AF Ackerman, Margaret E. Dugast, Anne-Sophie Alter, Galit BE Caskey, CT Austin, CP Hoxie, JA TI Emerging Concepts on the Role of Innate Immunity in the Prevention and Control of HIV Infection SO ANNUAL REVIEW OF MEDICINE, VOL 63 SE Annual Review of Medicine LA English DT Review; Book Chapter DE effector function; antibody-dependent cellular cytotoxicity; IgG Fe; antibody-dependent cellular viral inhibition; IgG; Fc gamma R ID DEPENDENT CELLULAR CYTOTOXICITY; SIMIAN IMMUNODEFICIENCY VIRUS; NEUTRALIZING ANTIBODY-RESPONSE; MANNOSE-BINDING LECTIN; GAMMA-RIIA GENOTYPE; RHESUS MACAQUES; FC-RECEPTOR; MONOCLONAL-ANTIBODIES; PASSIVE-IMMUNIZATION; HIV-1-INFECTED INDIVIDUALS AB While neutralizing antibodies can provide sterilizing protection from HIV infection via their variable domains, the antibody constant domain provides a functional link between innate and adaptive immunity and offers a means to harness the potent antiviral properties of a wide spectrum of innate immune effector cells. There has been a growing appreciation of the role of these effector mechanisms across fields from cancer immunotherapy to autoimmunity and infectious disease, as well as speculation that this mechanism may be responsible for the protection observed in the RV144 HIV vaccine trial. This review summarizes these extraneutralizing humoral immune activities, progress in defining the importance of these effector mechanisms during progression in HIV infection, and the potential impact that such vaccine-induced immune responses may have on protection from infection. C1 [Ackerman, Margaret E.; Dugast, Anne-Sophie; Alter, Galit] Massachusetts Gen Hosp, MIT, Ragon Inst, Charlestown, MA 02149 USA. [Ackerman, Margaret E.; Dugast, Anne-Sophie; Alter, Galit] Harvard Univ, Charlestown, MA 02149 USA. [Ackerman, Margaret E.] Dartmouth Coll, Thayer Sch Engn, Hanover, NH 03755 USA. RP Ackerman, ME (reprint author), Massachusetts Gen Hosp, MIT, Ragon Inst, Charlestown, MA 02149 USA. EM galter@partners.org RI Dugast, AnneSophie/L-9541-2015 NR 101 TC 35 Z9 35 U1 2 U2 11 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0897 USA SN 0066-4219 BN 978-0-8243-0563-5 J9 ANNU REV MED JI Annu. Rev. Med. PY 2012 VL 63 BP 113 EP 130 DI 10.1146/annurev-med-050310-085221 PG 18 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA BZK46 UT WOS:000301838400007 PM 22077718 ER PT S AU Flaherty, KT AF Flaherty, Keith T. BE Caskey, CT Austin, CP Hoxie, JA TI Targeting Metastatic Melanoma SO ANNUAL REVIEW OF MEDICINE, VOL 63 SE Annual Review of Medicine LA English DT Review; Book Chapter DE BRAF; vemurafenib; GSK2118436; MEK; CTLA-4 ID ULTRAVIOLET-RADIATION; BRAF; KINASE; MUTATIONS; RAF; CANCER; CELLS; INHIBITION; SUSCEPTIBILITY; EPIDEMIOLOGY AB Metastatic melanoma has historically been one of the most treatment-refractory types of cancer. Recent headway has been made in understanding the genetic underpinnings of this cancer. A subset of oncogenic events is amenable to targeting with drug therapy. BRAF-targeted therapies represent the first major breakthrough in systemic therapy for melanoma leveraging the new genetic knowledge. Ongoing translational research seeks to identify the most scientifically rational combination treatment strategies to build on single-agent targeted therapy. C1 Harvard Univ, Massachusetts Gen Hosp, Ctr Canc, Sch Med, Boston, MA 02114 USA. RP Flaherty, KT (reprint author), Harvard Univ, Massachusetts Gen Hosp, Ctr Canc, Sch Med, Boston, MA 02114 USA. EM kflaherty@partners.org NR 53 TC 28 Z9 28 U1 0 U2 7 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0897 USA SN 0066-4219 BN 978-0-8243-0563-5 J9 ANNU REV MED JI Annu. Rev. Med. PY 2012 VL 63 BP 171 EP 183 DI 10.1146/annurev-med-050410-105655 PG 13 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA BZK46 UT WOS:000301838400011 PM 22034865 ER PT S AU Fusco, DN Chung, RT AF Fusco, Dahlene N. Chung, Raymond T. BE Caskey, CT Austin, CP Hoxie, JA TI Novel Therapies for Hepatitis C: Insights from the Structure of the Virus SO ANNUAL REVIEW OF MEDICINE, VOL 63 SE Annual Review of Medicine LA English DT Review; Book Chapter DE HCV; direct acting antiviral agent (DAA); telaprevir; boceprevir; host cofactor inhibitor ID GENOTYPE 1 INFECTION; NS3/4A PROTEASE INHIBITOR; CHRONIC HCV INFECTION; PEGYLATED INTERFERON-ALPHA-2B; PEGINTERFERON ALPHA-2A; ANTIVIRAL ACTIVITY; RANDOMIZED-TRIAL; RNA REPLICATION; PLUS RIBAVIRIN; TELAPREVIR AB For the first time since the discovery of the hepatitis C virus (HCV), therapeutic options for hepatitis C have expanded. Several agents directly effective against HCV are now in development, including both direct-acting antiviral agents (DAAs) and host cofactor inhibitors. DAAs have been developed to inhibit several HCV proteins, including the NS3/4A serine protease, the NS5B RNA polymerase, NS5A, and NS4B. Host cofactor inhibitors include, but are not limited to, cyclophilin inhibitors, miR122 antagonists, and statins. Development of these agents represents a major advance in HCV therapeutics. This review provides a guide to HCV drugs in various stages of development, including an introduction to their mechanism of action, state of clinical development, efficacy, and side effects. C1 [Fusco, Dahlene N.; Chung, Raymond T.] Massachusetts Gen Hosp, Div Gastroenterol, Boston, MA 02114 USA. RP Fusco, DN (reprint author), Massachusetts Gen Hosp, Div Gastroenterol, Boston, MA 02114 USA. EM dnfusco@partners.org; rtchung@partners.org NR 69 TC 26 Z9 27 U1 1 U2 14 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0897 USA SN 0066-4219 BN 978-0-8243-0563-5 J9 ANNU REV MED JI Annu. Rev. Med. PY 2012 VL 63 BP 373 EP 387 DI 10.1146/annurev-med-042010-085715 PG 15 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA BZK46 UT WOS:000301838400025 PM 21942423 ER PT S AU Lai, TL Lavori, PW Shih, MC AF Lai, Tze Leung Lavori, Philip William Shih, Mei-Chiung BE Insel, PA Amara, SG Blaschke, TF TI Adaptive Trial Designs SO ANNUAL REVIEW OF PHARMACOLOGY AND TOXICOLOGY, VOL 52 SE Annual Review of Pharmacology and Toxicology LA English DT Review; Book Chapter DE group-sequential; variance spending; Bayesian methods; randomization ID SAMPLE-SIZE ADJUSTMENT; CLINICAL-TRIALS; CONDITIONAL POWER; ERROR AB We review adaptive designs for clinical trials, giving special attention to the control of the Type I error in late-phase confirmatory trials, when the trial planner wishes to adjust the final sample size of the study in response to an unblinded analysis of interim estimates of treatment effects. We point out that there is considerable inefficiency in using the adaptive designs that employ conditional power calculations to reestimate the sample size and that maintain the Type I error by using certain weighted test statistics. Although these adaptive designs have little advantage over familiar group-sequential designs, our review also describes recent developments in adaptive designs that are both flexible and efficient. We also discuss the use of Bayesian designs, when the context of use demands control over operating characteristics (Type I and II errors) and correction of the bias of estimated treatment effects. C1 [Lai, Tze Leung; Lavori, Philip William] Stanford Univ, Dept Stat, Stanford, CA 94305 USA. [Lai, Tze Leung; Lavori, Philip William; Shih, Mei-Chiung] Stanford Univ, Dept Hlth Res & Policy, Stanford, CA 94305 USA. [Shih, Mei-Chiung] US Dept Vet Affairs, Cooperat Studies Program, Mountain View, CA 94043 USA. RP Lai, TL (reprint author), Stanford Univ, Dept Stat, Stanford, CA 94305 USA. EM Lavori@Stanford.edu FU NCATS NIH HHS [UL1 TR001085]; NCI NIH HHS [P30 CA124435]; NCRR NIH HHS [UL1 RR025744] NR 24 TC 8 Z9 8 U1 0 U2 11 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0897 USA SN 0362-1642 BN 978-0-8243-0452-2 J9 ANNU REV PHARMACOL JI Annu. Rev. Pharmacol. Toxicol. PY 2012 VL 52 BP 101 EP 110 DI 10.1146/annurev-pharmtox-010611-134504 PG 10 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA BZK49 UT WOS:000301839600006 PM 21838549 ER PT S AU Peterson, RT MacRae, CA AF Peterson, Randall T. MacRae, Calum A. BE Insel, PA Amara, SG Blaschke, TF TI Systematic Approaches to Toxicology in the Zebrafish SO ANNUAL REVIEW OF PHARMACOLOGY AND TOXICOLOGY, VOL 52 SE Annual Review of Pharmacology and Toxicology LA English DT Review; Book Chapter DE pharmacogenetics; toxicogenetics; drug discovery; high-throughput screening; genomics ID ZINC-FINGER NUCLEASES; TAGGED TRIAZINE LIBRARY; LONG QT SYNDROME; CARDIAC-ARRHYTHMIA; TRANSGENIC ZEBRAFISH; CHEMICAL GENETICS; DRUG DISCOVERY; DANIO-RERIO; CAENORHABDITIS-ELEGANS; VERTEBRATE DEVELOPMENT AB As the current paradigms of drug discovery evolve, it has become clear that a more comprehensive understanding of the interactions between small molecules and organismal biology will be vital. The zebrafish is emerging as a complement to existing in vitro technologies and established preclinical in vivo models that can be scaled for high-throughput. In this review, we highlight the current status of zebrafish toxicology studies, identify potential future niches for the model in the drug development pipeline, and define the hurdles that must be overcome as zebrafish technologies are refined for systematic toxicology. C1 [Peterson, Randall T.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. RP Peterson, RT (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02115 USA. EM camacrae@bics.bwh.harvard.edu FU NINDS NIH HHS [NS 063563, NS 063733] NR 132 TC 64 Z9 66 U1 11 U2 46 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0897 USA SN 0362-1642 BN 978-0-8243-0452-2 J9 ANNU REV PHARMACOL JI Annu. Rev. Pharmacol. Toxicol. PY 2012 VL 52 BP 433 EP 453 DI 10.1146/annurev-pharmtox-010611-134751 PG 21 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA BZK49 UT WOS:000301839600021 PM 22017682 ER PT J AU Alam, HB AF Alam, H. B. TI Translational barriers and opportunities for emergency preservation and resuscitation in severe injuries SO BRITISH JOURNAL OF SURGERY LA English DT Review ID HYPOTHERMIC CIRCULATORY ARREST; TRAUMATIC BRAIN-INJURY; MILD THERAPEUTIC HYPOTHERMIA; PROFOUND HYPOTHERMIA; SWINE MODEL; CARDIAC-ARREST; HEMORRHAGIC-SHOCK; LETHAL HEMORRHAGE; CARDIOPULMONARY BYPASS; MODERATE HYPOTHERMIA AB Background: Hypothermia is commonly used for organ and tissue preservation in multiple clinical settings, but its role in the management of injured patients remains controversial. There is no doubt that temperature modulation is a powerful tool, and hypothermia has been shown to protect cells during ischaemia and reperfusion, decrease organ damage and improve survival. Yet hypothermia is a double-edged sword: unless carefully managed, its induction can be associated with a number of complications. Methods: A literature review was performed to include important papers that address the impact of hypothermia on key biological processes, and explore the potential therapeutic role of hypothermia in trauma/haemorrhage models. Results: No clinical studies have been conducted to test the therapeutic benefits of hypothermia in injured patients. However, numerous well designed animal studies support this concept. Despite excellent preclinical data, there are several potential barriers to translating hypothermia into clinical practice. Conclusion: Therapeutic hypothermia is a promising life-saving strategy. Appropriate patient selection requires a thorough understanding of how temperature modulation affects various biological mechanisms. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Trauma Emergency Surg & Surg Crit Care, Boston, MA 02114 USA. RP Alam, HB (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Trauma Emergency Surg & Surg Crit Care, 165 Cambridge St,Suite 810, Boston, MA 02114 USA. EM hbalam@partners.org FU National Institutes of Health [RO1 HL71698] FX Hypothermia research performed by H.B.A. was supported by a research grant from the National Institutes of Health (RO1 HL71698). NR 103 TC 12 Z9 12 U1 2 U2 3 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0007-1323 J9 BRIT J SURG JI Br. J. Surg. PD JAN PY 2012 VL 99 SU 1 BP 29 EP 39 DI 10.1002/bjs.7756 PG 11 WC Surgery SC Surgery GA 930PG UT WOS:000303151000008 PM 22441853 ER PT J AU Wen, XH Duda, T Pertzev, A Venkataraman, V Makino, CL Sharma, RK AF Wen, Xiao-Hong Duda, Teresa Pertzev, Alexandre Venkataraman, Venkateswar Makino, Clint L. Sharma, Rameshwar K. TI S100B Serves as a Ca2+ Sensor for ROS-GC1 Guanylate Cyclase in Cones but Not in Rods of the Murine Retina SO CELLULAR PHYSIOLOGY AND BIOCHEMISTRY LA English DT Article DE Guanylate cyclase; S100B; Phototransduction; Cyclic GMP; Calcium; Retina; Photoreceptors; Knockout mice; Synapse ID ACTIVATING PROTEIN; S-100 PROTEIN; MULLER CELLS; MICROSCOPIC IMMUNOCYTOCHEMISTRY; FUNCTIONAL-CHARACTERIZATION; SYNAPTOSOMAL FRACTIONS; BOVINE RETINA; MOUSE RETINA; WILD-TYPE; CD-GCAP AB Rod outer segment membrane guanylate cyclase (ROS-GC1) is a bimodal Ca2+ signal transduction switch. Lowering [Ca2+](i) from 200 to 20 nM progressively turns it "ON" as does raising [Ca2+](i) from 500 to 5000 nM. The mode operating at lower [Ca2+](i) plays a vital role in phototransduction in both rods and cones. The physiological function of the mode operating at elevated [Ca2+](i) is not known. Through comprehensive studies on mice involving gene deletions, biochemistry, immunohistochemistry, electroretinograms and single cell recordings, the present study demonstrates that the Ca2+-sensor S100B coexists with and is physiologically linked to ROS-GC1 in cones but not in rods. It up-regulates ROS-GC1 activity with a K-1/2 for Ca2+ greater than 500 nM and modulates the transmission of neural signals to cone ON-bipolar cells. Furthermore, a possibility is raised that under pathological conditions where [Ca2+](i) levels rise to and perhaps even enter the micromolar range, the S100B signaling switch will be turned "ON" causing an explosive production of CNG channel opening and further rise in [Ca2+](i) in cone outer segments. The findings define a new cone-specific Ca2+-dependent feature of photoreceptors and expand our understanding of the operational principles of phototransduction machinery. Copyright (C) 2012 S. Karger AG, Basel C1 [Wen, Xiao-Hong; Makino, Clint L.] Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02114 USA. [Wen, Xiao-Hong; Makino, Clint L.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Duda, Teresa; Pertzev, Alexandre; Sharma, Rameshwar K.] Salus Univ, Res Div Biochem & Mol Biol, Unit Regulatory & Mol Biol, Elkins Pk, PA USA. [Venkataraman, Venkateswar] Univ Med & Dent New Jersey SOM, Dept Cell Biol, Stratford, NJ USA. RP Wen, XH (reprint author), Massachusetts Eye & Ear Infirm, Dept Ophthalmol, 243 Charles St, Boston, MA 02114 USA. EM wenx@meei.harvard.edu OI Makino, Clint/0000-0002-6005-9069 FU Lions of Massachusetts; Pennsylvania Lions Sight Conservation and Eye Research Foundation; National Eye Institute [EY014104, EY011358]; National Heart Blood and Lung Institute [HL084584, S82701] FX We thank Drs. A. M. Dizhoor and A. Savchenko for the ERG recordings. This study was supported by the Lions of Massachusetts, the Pennsylvania Lions Sight Conservation and Eye Research Foundation, the National Eye Institute: EY014104, EY011358, the National Heart Blood and Lung Institute: HL084584 and S82701. The contents herein are the responsibility of the authors and do not necessarily represent the official views of any of the National Institutes of Health. NR 53 TC 10 Z9 10 U1 0 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1015-8987 J9 CELL PHYSIOL BIOCHEM JI Cell. Physiol. Biochem. PY 2012 VL 29 IS 3-4 BP 417 EP 430 DI 10.1159/000338496 PG 14 WC Cell Biology; Physiology SC Cell Biology; Physiology GA 925HS UT WOS:000302752600011 PM 22508049 ER PT J AU Van Dyke, TE AF Van Dyke, Thomas E. TI The impact of genotypes and immune reactivity on peri-implant inflammation: identification and therapeutic use of anti-inflammatory drugs and immunomodulators SO EUROPEAN JOURNAL OF ORAL IMPLANTOLOGY LA English DT Review DE genetic markers; inflammation; lipoxins; peri-implantitis; resolvins ID TRIGGERED 15-EPI-LIPOXIN A(4); POLYUNSATURATED FATTY-ACIDS; PERIODONTAL-DISEASE; STABLE ANALOGS; LIPOXIN A(4); RESOLVIN E1; IN-VIVO; APOPTOTIC NEUTROPHILS; CLINICAL-PARAMETERS; POTENT INHIBITORS AB Purpose: Peri-implantitis is a growing problem because of the increasing number of patients rehabilitated with oral implants. Predictors of susceptibility to peri-implantitis and pharmacological agents for the treatment of inflammatory peri-implantitis are of significant interest to the practicing community. The goal of this paper is to review the current literature relating to the impact of genotypes and immune reactivity on pen-implant inflammation and to identify the potential use of anti-inflammatory and immunomodulatory drugs. Materials and methods: A MEDLINE search of the relevant literature was performed and all related articles were evaluated. Results: There was little support in the literature for a specific genotype or phenotype of immune reactivity that could be reliably used as an indicator of susceptibility to pen-implant disease. Furthermore, no currently available anti-inflammatory drugs were identified that could be used long term for the treatment of inflammatory peri-implantitis. New pathways for the control of inflammation have been identified that have the potential for new pharmacologic therapies. The basis for these new discoveries is reviewed in some detail. Conclusions: While there are varying reports of associations of specific genotypes with peri-implantitis, the studies are inconsistent and generally underpowered precluding any interpretable pattern. Inflammatory peri-implantitis is associated with increased local inflammation, but no consistent systemic inflammatory markers have been identified. To date, no safe and effective anti-inflammatory therapy is known for the treatment of peri-implantitis. However, a new class of molecules in development for the active regulation and resolution of inflammation shows theoretical promise for the treatment of inflammatory lesions. C1 Forsyth Inst, Dept Periodontol, Cambridge, MA 02142 USA. RP Van Dyke, TE (reprint author), Forsyth Inst, Dept Periodontol, 245 1st St, Cambridge, MA 02142 USA. EM tvandyke@forsyth.org NR 73 TC 2 Z9 2 U1 0 U2 5 PU QUINTESSENCE PUBLISHING CO INC PI HANOVER PARK PA 4350 CHANDLER DRIVE, HANOVER PARK, IL 60133 USA SN 1756-2406 J9 EUR J ORAL IMPLANTOL JI Eur. J. Oral Implant. PY 2012 VL 5 SU S BP S51 EP S60 PG 10 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 928FG UT WOS:000302968000006 PM 22834394 ER PT J AU Delano-Wood, L Stricker, NH Sorg, SF Nation, DA Jak, AJ Woods, SP Libon, DJ Delisa, DC Frank, LR Bondi, MW AF Delano-Wood, Lisa Stricker, Nikki H. Sorg, Scott F. Nation, Daniel A. Jak, Amy J. Woods, Steven P. Libon, David J. Delisa, Dean C. Frank, Lawrence R. Bondi, Mark W. TI Posterior Cingulum White Matter Disruption and its Associations with Verbal Memory and Stroke Risk in Mild Cognitive Impairment SO JOURNAL OF ALZHEIMERS DISEASE LA English DT Article DE Aging; diffusion tensor imaging; memory; mild cognitive impairment; posterior cingulum; white matter ID EARLY ALZHEIMERS-DISEASE; VOXEL-BASED MORPHOMETRY; AGE-RELATED-CHANGES; MINI-MENTAL-STATE; IN-VIVO; APOLIPOPROTEIN-E; DIFFERENTIAL VULNERABILITY; AMYLOID DEPOSITION; MYELIN BREAKDOWN; DEFAULT NETWORK AB Medial temporal lobe and temporoparietal brain regions are among the earliest neocortical sites to undergo pathophysiologic alterations in Alzheimer's disease (AD), although the underlying white matter changes in these regions is less well known. We employed diffusion tensor imaging to evaluate early alterations in regional white matter integrity in participants diagnosed with mild cognitive impairment (MCI). The following regions of interests (ROIs) were examined: 1) anterior cingulum (AC); 2) posterior cingulum (PC); 3) genu of the corpus callosum; 4) splenium of the corpus callosum; and 5) as a control site for comparison, posterior limb of the internal capsule. Forty nondemented participants were divided into demographically-similar groups based on cognitive status (MCI: n = 20; normal control: n = 20), and fractional anisotropy (FA) estimates of each ROI were obtained. MCI participants showed greater posterior white matter (i.e., PC, splenium) but not anterior white matter (i.e., AC, genu) changes, after adjusting for age, stroke risk, and whole brain volume. FA differences of the posterior white matter were best accounted for by changes in radial but not axial diffusivity. PC FA was also significantly positively correlated with hippocampal volume as well as with performance on tests of verbal memory, whereas stroke risk was significantly correlated with genu FA and was unrelated to PC FA. When investigating subtypes of our MCI population, amnestic MCI participants showed lower PC white matter integrity relative to those with non-amnestic MCI. Findings implicate involvement of posterior microstructural white matter degeneration in the development of MCI-related cognitive changes and suggest that reduced FA of the PC may be a candidate neuroimaging marker of AD risk. C1 [Bondi, Mark W.] VA San Diego Healthcare Syst, Psychol Serv 116B, San Diego, CA 92161 USA. [Delano-Wood, Lisa; Sorg, Scott F.; Nation, Daniel A.; Jak, Amy J.; Woods, Steven P.; Delisa, Dean C.; Bondi, Mark W.] Univ Calif San Diego, Sch Med, Dept Psychiat, San Diego, CA 92103 USA. [Frank, Lawrence R.] Univ Calif San Diego, Sch Med, Dept Radiol, San Diego, CA 92103 USA. [Stricker, Nikki H.; Frank, Lawrence R.] VA Boston Healthcare Syst, Psychol Serv, Boston, MA USA. [Stricker, Nikki H.] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02118 USA. [Libon, David J.] Drexel Univ, Coll Med, Dept Neurol, Philadelphia, PA 19104 USA. RP Bondi, MW (reprint author), VA San Diego Healthcare Syst, Psychol Serv 116B, 3350 La Jolla Village Dr, San Diego, CA 92161 USA. EM mbondi@ucsd.edu FU National Institutes of Health [K24 AG026431, R01 AG12674, R01 MH64729, R01 MH75870, P50 AG05131]; Department of Veterans Affairs; Alzheimer's Association [IIRG 07-59343, NIRG 09-134067] FX This work was supported by grants from the National Institutes of Health (K24 AG026431, R01 AG12674, R01 MH64729, R01 MH75870, and P50 AG05131), by a Career Development Award and Merit Review Research Program from the Department of Veterans Affairs, and by Investigator Initiated (IIRG 07-59343) and New Investigator (NIRG 09-134067) Research Grants from the Alzheimer's Association. The authors gratefully acknowledge the assistance of staff, patients, and volunteers of the UCSD Alzheimer's Disease Research Center, and the UCSD Laboratory of Cognitive Imaging. NR 104 TC 18 Z9 22 U1 0 U2 4 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 1387-2877 J9 J ALZHEIMERS DIS JI J. Alzheimers Dis. PY 2012 VL 29 IS 3 BP 589 EP 603 DI 10.3233/JAD-2012-102103 PG 15 WC Neurosciences SC Neurosciences & Neurology GA 925UM UT WOS:000302787200011 PM 22466061 ER PT J AU Harris, AHS Kivlahan, D Barnett, PG Finney, JW AF Harris, Alex H. S. Kivlahan, Daniel Barnett, Paul G. Finney, John W. TI Longer Length of Stay Is Not Associated with Better Outcomes in VHA's Substance Abuse Residential Rehabilitation Treatment Programs SO JOURNAL OF BEHAVIORAL HEALTH SERVICES & RESEARCH LA English DT Article ID ADDICTION SEVERITY INDEX; PATTERN-MIXTURE MODELS; MISSING DATA; TIME SPENT; ALCOHOLISM; CARE AB Are longer stays in Veterans Health Administration (VHA) substance abuse residential rehabilitation treatment programs (SARRTPs) associated with better substance-related outcomes? To investigate, up to 50 new patients were randomly selected from each of 28 randomly selected programs (1,307 patients). The goal was to examine if patient and program average length of stay (ALOS) were associated with improvement on Addiction Severity Index (ASI) Alcohol and Drug composite scores in covariate-adjusted, multi-level regression models. Patients in programs with ALOS greater than 90 days tended to have more mental health treatment prior to the index episode and less severe substance-related symptoms, but more homelessness. At follow-up, programs longer than 90 days had the least improvement in the ASI Alcohol composite and significantly less improvement than programs with ALOSs of 15 to 30 and 31 to 45 days (both p<0.05). Therefore, in VHA SARRTPs, ALOS greater than 90 days cannot be justified by the substance use disorder severity of the patients served or the magnitude of the clinical improvement observed. C1 [Harris, Alex H. S.; Barnett, Paul G.; Finney, John W.] Stanford Univ, Ctr Hlth Care Evaluat, VA Palo Alto Hlth Care Syst, Sch Med, Menlo Pk, CA 94025 USA. [Kivlahan, Daniel] Univ Washington, Sch Med, VA Puget Sound Hlth Care Syst, Seattle, WA USA. [Barnett, Paul G.] Stanford Univ, Hlth Econ Resource Ctr, VA Palo Alto Hlth Care Syst, Sch Med, Menlo Pk, CA 94025 USA. RP Harris, AHS (reprint author), Stanford Univ, Ctr Hlth Care Evaluat, VA Palo Alto Hlth Care Syst, Sch Med, 795 Willow Rd,MC152, Menlo Pk, CA 94025 USA. EM alexander.harris2@va.gov; Daniel.Kivlahan@va.govPhD; Paul.Barnett@va.gov; John.Finney@va.gov FU VA Substance Use Disorders Quality Enhancement Research Initiative; Health Service Research and Development Service [RRP 09-393, SUS 99-015] FX This study was funded by the VA Substance Use Disorders Quality Enhancement Research Initiative and Health Service Research and Development Service (grants nos. RRP 09-393 and SUS 99-015). NR 27 TC 2 Z9 2 U1 3 U2 9 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1094-3412 J9 J BEHAV HEALTH SER R JI J. Behav. Health Serv. Res. PD JAN PY 2012 VL 39 IS 1 BP 68 EP 79 DI 10.1007/s11414-011-9250-2 PG 12 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 928QZ UT WOS:000302999300007 PM 21732222 ER PT J AU Goldfarb-Rumyantzev, AS Rout, P Sandhu, GS Barenbaum, A Patibandla, BK Narra, A Chawla, V Williams, M AF Goldfarb-Rumyantzev, Alexander S. Rout, Preeti Sandhu, Gurprataap S. Barenbaum, Anna Patibandla, Bhanu K. Narra, Akshita Chawla, Varun Williams, Mark TI Social adaptability index predicts overall mortality in patients with diabetes SO JOURNAL OF DIABETES AND ITS COMPLICATIONS LA English DT Article DE Diabetes; Social adaptability index; Outcome; Epidemiology; Mortality; Prediction ID QUALITY-OF-CARE; SOCIOECONOMIC-STATUS; EDUCATIONAL DISPARITIES; MARITAL-STATUS; COMPLICATIONS; SURVIVAL; OUTCOMES; ASSOCIATION; POPULATION; RECIPIENT AB Background: A quantifiable assessment of socioeconomic status and its bearing on clinical outcome in patients with diabetes is lacking. The social adaptability index (SAI) has previously been validated in the general population and in patients with chronic kidney disease, including those on dialysis and with kidney transplant. We hypothesize that SAI could be used in diabetes practice to identify a disadvantaged population at risk for inferior outcomes. Methods: The NHANES-3 database of patients who have diabetes was analyzed. The association of the SAI (calculated as the linear combination of indicators of education status, employment, income, marital status, and substance abuse) with patient survival was evaluated using Cox model. Results: The study population consisted of 1634 subjects with diabetes mellitus with mean age of 61.9 +/- 15.3 years; 40.9% males; 38.5% white, 27.7% African American, and 31.3% Mexican American. The highest SAI was in whites (6.9 +/- 2.5), followed by Mexican Americans (6.5 +/- 2.3), and then African Americans (6.1 +/- 2.6) (ANOVA, P<.001). SAI was higher in subjects living in metropolitan areas (6.8 +/- 2.6) compared to the rural population (6.3 +/- 2.4) (T test, P<.001). Also, SAI was greater in males (7.1 +/- 2.4) than in females (6.1 2.4) (T test, P<.001). SAI had significant association with survival (hazard ratio 0.9, P<.001) in the entire study population and in most of the subgroups (divided by race, sex, and urban/rural location). Furthermore, SAI divided into tertiles (<= 5, 6 to 8, >8) demonstrated a significant and "dose-dependent" association with survival. Conclusion: Social adaptability index is associated with mortality in the diabetic population and is useful in identifying individuals who are at risk for inferior outcomes. (C) 2012 Elsevier Inc. All rights reserved. C1 [Goldfarb-Rumyantzev, Alexander S.; Rout, Preeti; Sandhu, Gurprataap S.; Patibandla, Bhanu K.; Narra, Akshita; Chawla, Varun; Williams, Mark] Beth Israel Deaconess Med Ctr, Div Nephrol, Boston, MA 02215 USA. [Goldfarb-Rumyantzev, Alexander S.; Rout, Preeti; Sandhu, Gurprataap S.; Patibandla, Bhanu K.; Narra, Akshita; Chawla, Varun; Williams, Mark] Harvard Univ, Sch Med, Boston, MA USA. [Goldfarb-Rumyantzev, Alexander S.] Beth Israel Deaconess Med Ctr, Transplant Inst, Boston, MA 02215 USA. [Barenbaum, Anna] Tel Aviv Univ, IL-69978 Tel Aviv, Israel. [Williams, Mark] Joslin Diabet Ctr, Div Nephrol, Boston, MA 02215 USA. RP Goldfarb-Rumyantzev, AS (reprint author), Beth Israel Deaconess Med Ctr, Div Nephrol, 185 Pilgrim Rd,FA 832, Boston, MA 02215 USA. EM agoldfar@bidmc.harvard.edu NR 37 TC 5 Z9 5 U1 0 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1056-8727 J9 J DIABETES COMPLICAT JI J. Diabetes Complications PD JAN-FEB PY 2012 VL 26 IS 1 BP 44 EP 49 DI 10.1016/j.jdiacomp.2011.12.002 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 925JZ UT WOS:000302758800008 PM 22321220 ER PT J AU Tierney, K AF Tierney, Kathryn TI Therapeutic choices, and the nurse practitioner's role, in type 2 diabetes when metformin alone is no longer enough SO JOURNAL OF THE AMERICAN ACADEMY OF NURSE PRACTITIONERS LA English DT Article DE Type 2 diabetes; treatments; nurse practitioner; patient education ID INCRETIN-BASED THERAPIES; TWICE-DAILY EXENATIDE; HUMAN GLP-1 ANALOG; OPEN-LABEL TRIAL; GLYCEMIC CONTROL; COMBINATION THERAPY; PLUS METFORMIN; PARALLEL-GROUP; LIRAGLUTIDE; EFFICACY AB Purpose: This article provides an overview of the currently available treatments for type 2 diabetes (T2D), outlining the most up to date information to assist nurse practitioners (NPs) to make informed prescribing decisions for T2D therapy once patients are no longer able to maintain blood glucose control using lifestyle modification and/or metformin therapy. Data sources: Published guidelines for the management of T2D, review articles, primary manuscripts, and FDA prescribing information documents. Conclusions: In the past, options for the treatment of T2D were limited. However, there is now an ever increasing number of available therapeutic choices for T2D, that, as well as glycemic control, offer significant additional benefits, particularly in terms of reducing hypoglycemic risk and weight gain. Consequently, these newer agents provide both patients and NPs with a much greater choice for ongoing therapy. Implications for practice: The differing benefits and risk profiles shown by the currently available antidiabetic treatments provide NPs with a unique opportunity to tailor treatment plans more closely to the requirements of each patient. This approach can ensure that the right drug reaches the right patient, which should in turn promote greater treatment compliance and improved outcomes, ultimately slowing disease progression. C1 Hosp Cent Connecticut, Joslin Diabet Ctr, New Britain, CT 06051 USA. RP Tierney, K (reprint author), Hosp Cent Connecticut, Joslin Diabet Ctr, 100 Grand St, New Britain, CT 06051 USA. EM ktierney@thocc.org FU Novo Nordisk Inc, Princeton, NJ, USA FX The assistance of Watermeadow Medical, Witney, UK, funded by Novo Nordisk Inc, Princeton, NJ, USA, in preparing this article is gratefully acknowledged. NR 72 TC 2 Z9 2 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1041-2972 J9 J AM ACAD NURSE PRAC JI J. Am. Acad. Nurse Pract. PY 2012 VL 24 SU 1 BP 234 EP 248 DI 10.1111/j.1745-7599.2012.00720.x PG 15 WC Health Care Sciences & Services; Nursing SC Health Care Sciences & Services; Nursing GA 926OH UT WOS:000302840200002 PM 22564100 ER PT S AU Sun, W Lu, Y Stewart, JB Bifano, TG Lin, CP AF Sun, Wei Lu, Yang Stewart, Jason B. Bifano, Thomas G. Lin, Charles P. BE Olivier, SS Bifano, TG Kubby, J TI Critical considerations of pupil alignment to achieve open-loop control of MEMS deformable mirror in non-linear laser scanning fluorescence microscopy SO MEMS ADAPTIVE OPTICS VI SE Proceedings of SPIE LA English DT Proceedings Paper CT Conference on MEMS Adaptive Optics VI CY JAN 24-26, 2012 CL San Francisco, CA SP SPIE, Dyoptyka, VUZIX Corp DE Adaptive optics; MEMS deformable mirror; open-loop control; Shack-Hartmann wavefront sensor AB In this paper we present an alignment methodology for a non-linear laser scanning fluorescence microscopic imaging system integrated with a MEMS deformable mirror that is used to compensate microscope aberrations and improve sample image quality. The procedure uses an accurate open-loop control mechanism of the MEMS DM, a high resolution CMOS camera and a compact Shack-Hartmann wavefront sensor. The success of the indirect AO control method used by the microscope to compensate aberrations requires careful alignment of the optical system, specifically the DM conjugate planes in the scanning laser optical path. Considerations of this procedure are presented here, in addition to an assessment of the final accuracy of the alignment task is presented, by verifying the pupil conjugation and wavefront response. This method can also serve as a regular check-up of the system's performance and trouble-shoot for system misalignment. C1 [Sun, Wei; Lin, Charles P.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Adv Microscopy Program, Boston, MA 02114 USA. RP Sun, W (reprint author), Massachusetts Gen Hosp, Wellman Ctr Photomed, Adv Microscopy Program, 185 Cambridge St, Boston, MA 02114 USA. EM wsun@buphy.bu.edu RI Bifano, Thomas/E-6412-2013 OI Bifano, Thomas/0000-0003-4952-2515 NR 17 TC 1 Z9 1 U1 1 U2 3 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-0-8194-8896-1 J9 PROC SPIE PY 2012 VL 8253 AR 82530H DI 10.1117/12.909652 PG 7 WC Engineering, Electrical & Electronic; Materials Science, Multidisciplinary; Optics SC Engineering; Materials Science; Optics GA BZS20 UT WOS:000302692300014 ER PT S AU Gagnon, L Yucel, MA Dehaes, M Cooper, RJ Perdue, KL Selb, J Boas, DA AF Gagnon, Louis Yuecel, Meryem A. Dehaes, Mathieu Cooper, Robert J. Perdue, Katherine L. Selb, Juliette Boas, David A. BE Azar, FS Intes, X TI Quantifying the cortical contribution to the NIRS signal using simultaneous NIRS-BOLD measurements SO MULTIMODAL BIOMEDICAL IMAGING VII SE Proceedings of SPIE LA English DT Proceedings Paper CT Conference on Multimodal Biomedical Imaging VII CY JAN 21-22, 2012 CL San Francisco, CA SP SPIE DE Blood flow measurement; Near-infrared spectroscopy; Speckle ID NEAR-INFRARED SPECTROSCOPY; CEREBRAL OXYGEN-METABOLISM; BRAIN ACTIVATION; BALLOON MODEL; BLOOD-VOLUME; RESPONSES; DYNAMICS; FLOW; RESOLUTION; ACCURACY AB Near-Infrared Spectroscopy (NIRS) measures the functional hemodynamic response occuring at the surface of the cortex. Large pial veins are located above the surface of the cerebral cortex. Following activation, these veins exhibit oxygenation changes but their volume likely stays constant. The back-reflection geometry of the NIRS measurement renders the signal very sensitive to these superficial pial veins. As such, the measured NIRS signal contains contributions from both the cortical region as well as the pial vasculature. In this work, the cortical contribution to the NIRS signal was investigated using (1) Monte Carlo simulations over a realistic geometry constructed from anatomical and vascular MRI and (2) multimodal NIRS-BOLD recordings during motor stimulation. A good agreement was found between the simulations and the modeling analysis of in vivo measurements. Our results suggest that the cortical contribution to the deoxyhemoglobin signal change (Delta HbR) is equal to 16-22% of the cortical contribution to the total hemoglobin signal change (Delta HbT). Similarly, the cortical contribution of the oxyhemoglobin signal change (Delta HbO) is equal to 73-79% of the cortical contribution to the Delta HbT signal. These results suggest that Delta HbT is far less sensitive to pial vein contamination and therefore, it is likely that the Delta HbT signal provides better spatial specificity and should be used instead of Delta HbO or Delta HbR to map cerebral activity with NIRS. While different stimuli will result in different pial vein contributions, our finger tapping results do reveal the importance of considering the pial contribution. C1 [Gagnon, Louis; Yuecel, Meryem A.; Cooper, Robert J.; Selb, Juliette; Boas, David A.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging,Dept Radi, Charlestown, MA 02129 USA. RP Gagnon, L (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging,Dept Radi, Charlestown, MA 02129 USA. EM lgagnon@nmr.mgh.harvard.edu NR 31 TC 0 Z9 0 U1 0 U2 2 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-0-8194-8859-6 J9 PROC SPIE PY 2012 VL 8216 AR 82160F DI 10.1117/12.909629 PG 12 WC Engineering, Biomedical; Optics; Imaging Science & Photographic Technology SC Engineering; Optics; Imaging Science & Photographic Technology GA BZR45 UT WOS:000302569400009 ER PT J AU Dawes, SE Palmer, BW Meeks, T Golshan, S Kasckow, J Mohamed, S Zisook, S AF Dawes, Sharron E. Palmer, Barton W. Meeks, Thomas Golshan, Shahrokh Kasckow, John Mohamed, Somaia Zisook, Sidney TI Does Antidepressant Treatment Improve Cognition in Older People with Schizophrenia or Schizoaffective Disorder and Comorbid Subsyndromal Depression? SO NEUROPSYCHOBIOLOGY LA English DT Article DE Schizophrenia; Citalopram; Cognition; Subsyndromal depression ID BIPOLAR DISORDER; PERFORMANCE; FAMILIES; SCALE AB Background: Subsyndromal symptoms of depression (SSD) in patients with schizophrenia are common and clinically important. While treatment of depression in major depressive disorder may partially ameliorate cognitive deficits, the cognitive effects of antidepressant medications in patients with schizophrenia or schizoaffective disorder and SSD are unknown. Methods: The goal of this study was to assess the impact of SSD and their treatment on cognition in participants with schizophrenia or schizoaffective disorder aged 6 40 years. Participants were randomly assigned to a flexible dose treatment with citalopram or placebo augmentation of their current medication for 12 weeks. An ANCOVA compared improvement in the cognitive composite scores, and a linear model determined the moderation of cognition on treatment effects based on the Hamilton Depression Rating Scale and the Calgary Depression Rating Scale scores between treatment groups. Results: There were no differences between the citalopram and placebo groups in changes in cognition. Baseline cognitive status did not moderate antidepressant treatment response. Conclusions: Although there are other cogent reasons why SSD in schizophrenia warrant direct intervention, treatment does not substantially affect the level of cognitive functioning. Given the effects of cognitive deficits associated with schizophrenia on functional disability, there remains an ongoing need to identify effective means of directly ameliorating them. Copyright (C) 2012 S. Karger AG, Basel C1 [Zisook, Sidney] Univ Calif San Diego, Dept Psychiat, Div Geriatr Psychiat, San Diego, CA 92161 USA. [Golshan, Shahrokh; Zisook, Sidney] Vet Affairs San Diego Healthcare Syst, Dept Psychiat, San Diego, CA USA. [Palmer, Barton W.; Zisook, Sidney] San Diego Vet Med Res Fdn, San Diego, CA USA. [Kasckow, John] MIRECC, VA Pittsburgh Hlth Care Syst, Pittsburgh, PA USA. [Kasckow, John] CHERP, Pittsburgh, PA USA. [Kasckow, John] UPMC Western Psychiat Inst & Clin, Pittsburgh, PA USA. [Mohamed, Somaia] Vet Affairs New England Mental Illness Res Educ &, West Haven, CT USA. [Mohamed, Somaia] Yale Univ, Sch Med, Dept Psychiat, New Haven, CT USA. RP Zisook, S (reprint author), Univ Calif San Diego, Dept Psychiat, Div Geriatr Psychiat, 3350 La Jolla Village Dr, San Diego, CA 92161 USA. EM szisook@ucsd.edu FU Citalopram Augmentation of Older Patients with Schizophrenia [RO-1 MH 063931]; NIMH [MH66248, MH19934, P30 MH080002]; Department of Veterans Affairs; VISN 4 MIRECC [R01 MH6398]; VISN 4 CPPF FX This work was supported by RO-1 MH 063931 Citalopram Augmentation of Older Patients with Schizophrenia (S.Z.), NIMH grants MH66248, MH19934, P30 MH080002 and the Department of Veterans Affairs. J.K. was supported by R01 MH6398, the VISN 4 MIRECC and a VISN 4 CPPF award. NR 24 TC 3 Z9 3 U1 1 U2 2 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0302-282X EI 1423-0224 J9 NEUROPSYCHOBIOLOGY JI Neuropsychobiology PY 2012 VL 65 IS 3 BP 168 EP 172 DI 10.1159/000331141 PG 5 WC Neurosciences; Psychiatry; Psychology SC Neurosciences & Neurology; Psychiatry; Psychology GA 926ZX UT WOS:000302875300009 PM 22456094 ER PT J AU Colpo, A Wilson, FH Nardi, V Hochberg, E AF Colpo, Anna Wilson, Frederick H. Nardi, Valentina Hochberg, Ephraim TI Administration of Vincristine in a Patient with Machado-Joseph Disease SO ONCOLOGY LA English DT Article DE Machado-Joseph disease; Spinocerebellar ataxia type 3; Vinca alkaloid; Vincristine ID MARIE-TOOTH-DISEASE; B-CELL LYMPHOMA; HEREDITARY NEUROPATHY; PERIPHERAL NEUROPATHY; NEUROTOXICITY; CHEMOTHERAPY; CHOP AB Chemotherapy-induced peripheral neurotoxicity is a major problem because it represents the dose-limiting side effect of a significant number of antineoplastic drugs, such as vinca alkaloids. Hereditary neuropathies usually predispose to severe vincristine neurotoxicity. Here, we report the case of a 56-year-old man with Machado-Joseph disease, also known as spinocerebellar ataxia type 3, treated with a vinca alkaloid without exacerbation of neurological symptoms. C1 [Hochberg, Ephraim] Massachusetts Gen Hosp, Ctr Canc, Div Haematol Oncol, Boston, MA 02114 USA. [Nardi, Valentina] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Colpo, Anna] Univ Padua, Sch Med, Dept Med Haematol & Clin Immunol, Padua, Italy. RP Hochberg, E (reprint author), Massachusetts Gen Hosp, Ctr Canc, Div Haematol Oncol, Yawkey Bldg,55 Fruit St, Boston, MA 02114 USA. EM ehochberg@partners.org FU NCI NIH HHS [T32 CA009172] NR 16 TC 1 Z9 1 U1 0 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0030-2414 J9 ONCOLOGY-BASEL JI Oncology PY 2012 VL 82 IS 3 BP 165 EP 167 DI 10.1159/000336602 PG 3 WC Oncology SC Oncology GA 926ZN UT WOS:000302873800005 PM 22433430 ER PT S AU Alt, C Lin, CP AF Alt, Clemens Lin, Charles P. BE Manns, F Soderberg, PG Ho, A TI In vivo quantification of microglia dynamics with a scanning laser ophthalmoscope in a mouse model of focal laser injury SO OPHTHALMIC TECHNOLOGIES XXII SE Proceedings of SPIE LA English DT Proceedings Paper CT Conference on Ophthalmic Technologies XXII/SPIE Photonics West BiOS Meeting CY JAN 21-22, 2012 CL San Francisco, CA SP SPIE ID SELECTIVE PHOTOTHERMOLYSIS; RETINAL MICROGLIA; RESTING MICROGLIA; CELLS; EYE; MICROSCOPY; TRACKING AB Microglia are the resident immune cells of the central nervous system and play a crucial role in maintaining neuronal health and function. Their dynamic behavior, that is, the constant extension and retraction of microglia processes, is thought to be critical for communication between microglia and their cellular neighbors, such as neurons, astrocytes and vascular endothelial cells. Here, we investigated the morphology and dynamics of retinal microglia in vivo under normal conditions and in response to focal laser injury of blood vessel endothelial wall, using a scanning laser ophthalmoscope (SLO) designed specifically for imaging the retina of live mice. The multichannel confocal imaging system allows retinal microstructure, such as the processes of microglia and retinal vasculature, to be visualized simultaneously. In order to generate focal laser injury, a photocoagulator based on a continuous wave (cw) laser was coupled into the SLO. An acousto-optic modulator chopped pulses from the cw laser. A tip-tilt-scanner was used to direct the laser beam into a blood vessel of interest under SLO image guidance. Mild coagulation was produced using millisecond-long pulses. Microglia react dynamically to focal laser injury of blood vessel endothelial walls. Under normal conditions, microglia somas remain stationary and the processes probe a territory of their immediate environment. In response to local injury, process movement velocity approximately doubles within minutes after injury. Moreover, the previously unpolarized process movement assumes a distinct directionality towards the injury site, indicating signaling between the injured tissue and the microglia. In vivo retinal imaging is a powerful tool for understanding the dynamic behavior of retinal cells. C1 [Alt, Clemens] Harvard Univ, Adv Microscopy Program, Wellman Ctr Photomed, Massachusetts Gen Hosp,Med Sch, Cambridge, MA 02138 USA. RP Alt, C (reprint author), Harvard Univ, Adv Microscopy Program, Wellman Ctr Photomed, Massachusetts Gen Hosp,Med Sch, Cambridge, MA 02138 USA. NR 25 TC 3 Z9 3 U1 1 U2 4 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-0-8194-8852-7 J9 PROC SPIE PY 2012 VL 8209 AR 820907 DI 10.1117/12.909141 PG 9 WC Optics; Radiology, Nuclear Medicine & Medical Imaging SC Optics; Radiology, Nuclear Medicine & Medical Imaging GA BZR33 UT WOS:000302553200002 ER PT S AU Glidden, MD Massodi, I Rizvi, I Celli, JP Hasan, T AF Glidden, Michael D. Massodi, Iqbal Rizvi, Imran Celli, Jonathan P. Hasan, Tayyaba BE Kessel, DH Hasan, T TI Probing tumor-stroma interactions and response to photodynamic therapy in a 3D pancreatic cancer-fibroblast co-culture model SO OPTICAL METHODS FOR TUMOR TREATMENT AND DETECTION: MECHANISMS AND TECHNIQUES IN PHOTODYNAMIC THERAPY XXI SE Proceedings of SPIE LA English DT Proceedings Paper CT Conference on Optical Methods for Tumor Treatment and Detection - Mechanisms and Techniques in Photodynamic Therapy XXI CY JAN 21-22, 2012 CL San Francisco, CA SP SPIE DE Fibroblast Co-Cultures; Pancreatic Cancer; Tumor-Stroma Interactions; Image Processing; Photodynamic Therapy; PDT; In Vitro Model ID PROGRESSION AB Pancreatic ductal adenocarcinoma is a lethal disease that is often unresectable by the time of diagnosis and is typically non-responsive to chemo- and radiotherapy, resulting in a five year survival of only 3%. Tumors of the pancreas are characterized by a dense fibrous stroma rich in extracellular matrix proteins, which is implicated in poor therapeutic response, though its precise roles remain poorly understood. Indeed, while the use of therapeutics that target the stroma is an emerging paradigm in the clinical management of this disease, the primary focus of such efforts is to enhance drug penetration through dense fibrous stroma and it is unclear to what extent the characteristically rigid stroma of pancreatic tumors imparts drug resistance by acting as a complex signaling partner, or merely as a physical barrier for drug delivery. Here we use 3D in vitro co-cultures of pancreatic cancer cells and normal human fibroblasts as a model system to study heterotypic interactions between these populations. Leveraging this in vitro model along with image-based methods for quantification of growth and therapeutic endpoints, we characterize these co-cultures and examine the role of verteporfin-based photodynamic therapy (PDT) for targeting tumor-fibroblast interactions in pancreatic tumors. C1 [Glidden, Michael D.; Massodi, Iqbal; Rizvi, Imran; Celli, Jonathan P.; Hasan, Tayyaba] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. RP Glidden, MD (reprint author), Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. EM jonathan.celli@umb.edu; thasan@partners.org OI Rizvi, Imran/0000-0001-9673-4700 NR 15 TC 1 Z9 1 U1 2 U2 8 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-0-8194-8853-4 J9 PROC SPIE PY 2012 VL 8210 AR 821006 DI 10.1117/12.910924 PG 8 WC Optics; Radiology, Nuclear Medicine & Medical Imaging SC Optics; Radiology, Nuclear Medicine & Medical Imaging GA BZR69 UT WOS:000302600500004 ER PT J AU Jeger, V Willi, S Liu, T Yeh, DD DeMoya, M Zimmermann, H Exadaktylos, AK AF Jeger, Victor Willi, Sandra Liu, Tun Yeh, Daniel D. DeMoya, Marc Zimmermann, Heinz Exadaktylos, Aristomenis K. TI The Rapid TEG alpha-Angle May Be a Sensitive Predictor of Transfusion in Moderately Injured Blunt Trauma Patients SO SCIENTIFIC WORLD JOURNAL LA English DT Article ID THROMBELASTOGRAPHY; COAGULOPATHY AB Background. To guide the administration of blood products, coagulation screening of trauma patients should be fast and accurate. The purpose of this study was to identify the correlation between CCT and TEG in trauma, to determine which CCT or TEG parameter is most sensitive in predicting transfusion in trauma, and to define TEG cut-off points for trauma care. Methods. A six-month, prospective observational study of 76 adult patients with suspected multiple injuries was conducted at a Level 1 trauma centre of a university hospital. Physicians blinded to TEG results made the decision to transfuse based on clinical evaluation. Results. The study results showed that conventional coagulation tests correlate moderately with Rapid TEG parameters (R: 0.44-0.61). Kaolin and Rapid TEG were more sensitive than CCTs, and the Rapid TEG a-Angle was identified as the single parameter with the greatest sensitivity (84%) and validity (77%) at a cut-off of 74.7 degrees. When the Rapid TEG a-Angle was combined with heart rate >75 bpm, or haematocrit <41%, sensitivity (84%, 88%) and specificity (75%, 73%) were improved. Conclusion. Cutoff points for transfusion can be determined with the Rapid TEG a-Angle and can provide better sensitivity than CCTs, but a larger study population is needed to reproduce this finding. C1 [Jeger, Victor; Willi, Sandra; Zimmermann, Heinz; Exadaktylos, Aristomenis K.] Univ Hosp Inselspital Bern, Dept Emergency Med, CH-3010 Bern, Switzerland. [Liu, Tun] Haemonetics Corp, Braintree, MA 02184 USA. [Yeh, Daniel D.; DeMoya, Marc] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Jeger, V (reprint author), Univ Hosp Inselspital Bern, Dept Emergency Med, CH-3010 Bern, Switzerland. EM victor.jeger@students.unibe.ch FU AACC (American Academy of Clinical Chemistry) FX This study was supported by the "AACC (American Academy of Clinical Chemistry) Critical and Point-of-Care Testing Research Grant 2009". An abstract of this study has been presented at the International Symposium on Intensive Care and Emergency Medicine 2011, Brussels, Belgium. NR 17 TC 11 Z9 11 U1 0 U2 1 PU HINDAWI PUBLISHING CORPORATION PI NEW YORK PA 410 PARK AVENUE, 15TH FLOOR, #287 PMB, NEW YORK, NY 10022 USA SN 1537-744X J9 SCI WORLD J JI Sci. World J. PY 2012 AR 821794 DI 10.1100/2012/821794 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 928TM UT WOS:000303008100001 ER PT S AU Bautista, PA Yagi, Y AF Bautista, Pinky A. Yagi, Yukako BE VoDinh, T MahadevanJansen, A Grundfest, WS TI Multispectral image enhancement by spectral shifting SO ADVANCED BIOMEDICAL AND CLINICAL DIAGNOSTIC SYSTEMS X SE Proceedings of SPIE LA English DT Proceedings Paper CT Conference on Advanced Biomedical and Clinical Diagnostic Systems X CY JAN 22-24, 2012 CL San Francisco, CA SP SPIE DE Multispectral enhancement; spectral enhancement; multispectral visualization; pathology; multispectral imaging ID TRANSFORM AB A multispectral enhancement method that preserves the natural color of the background pixels was previously proposed. In such method, the band for enhancement was identified from the N-band spectral residual-error of the objects of interest. The spectral residual-error is determined by taking the difference between the original spectrum of the pixel and its estimate using M << N principal components in principal component analysis (PCA). However, for stained histopathology images where staining variations do exist even among tissue sections the band for enhancement could vary. In this work, we introduced a modification to the previously proposed multispectral enhancement method such that the band for enhancement could be specified independent of the spectral residual-error configurations. In the proposed modification the original spectral transmittance of the pixels at each band are shifted by the product between the spectral residual-error coefficient, which is the most dominant PC coefficient of the spectral error, of the pixel and the weighting factor assigned by the user to each band. Results of our experiments on H&E stained sections of liver tissue show that the proposed modification delivers more consistent enhancement results compared to the previously proposed methods, especially when the band for enhancement varies. C1 [Bautista, Pinky A.; Yagi, Yukako] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Bautista, PA (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. NR 7 TC 0 Z9 0 U1 0 U2 0 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-0-8194-8857-2 J9 PROC SPIE PY 2012 VL 8214 AR 82140K DI 10.1117/12.910060 PG 7 WC Engineering, Biomedical; Optics; Imaging Science & Photographic Technology SC Engineering; Optics; Imaging Science & Photographic Technology GA BZR44 UT WOS:000302567700011 ER PT J AU Januzzi, JL AF Januzzi, James L., Jr. TI The role of natriuretic peptide testing in guiding chronic heart failure management: Review of available data and recommendations for use SO ARCHIVES OF CARDIOVASCULAR DISEASES LA English DT Review DE Natriuretic peptides; Heart failure; Outcomes ID LEFT-VENTRICULAR HYPERTROPHY; NT-PROBNP LEVELS; GUIDED THERAPY; VAL-HEFT; SYSTOLIC DYSFUNCTION; FILLING PRESSURES; RANDOMIZED-TRIAL; PROGNOSTIC VALUE; TERMINAL PROBNP; BETA-BLOCKER AB The care of patients with heart failure can be challenging, with few objective tools available to assist in therapy decision-making. Natriuretic peptides are powerfully prognostic biomarkers in patients with heart failure and may represent an objective target for therapy. Accordingly, the use of biomarker-guided care with either B-type natriuretic peptide (BNP) or amino-terminal pro-B-type natriuretic peptide (NT-proBNP) has been recently explored. Over the past few years, a number of studies with heterogeneous inclusion criteria, methods and results have been performed. We have reviewed the available literature, summarizing the results of biomarker-guided heart failure trials and deriving recommendations for optimal application of biomarker-guided heart failure care based on the experience gained. In general, positive studies had low BNP or NT-proBNP target concentrations (similar to 100 pg/mL and similar to 1000 pg/mL, respectively) and achieved lower natriuretic peptide concentrations compared with standard care. Patients in the biomarker-guided arms of the studies typically received more aggressive heart failure care and had no excess adverse outcomes. In the recent ProBNP Outpatient Tailored Chronic Heart Failure Therapy (PROTECT) study, patients treated with biomarker-guided care also had improved quality of life and significantly better reverse remodeling on echocardiography compared with patients who received standard care. In conclusion, heart failure therapy guided by a goal to reduce natriuretic peptide concentrations below prognostically-meaningful levels results in more aggressive heart failure care, is well tolerated and is associated with superior outcomes. (C) 2011 Elsevier Masson SAS. All rights reserved. C1 Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. RP Januzzi, JL (reprint author), Massachusetts Gen Hosp, Div Cardiol, Yawkey 5984, Boston, MA 02114 USA. EM JJanuzzi@partners.org FU Roche Diagnostics; Critical Diagnostics; Siemens Diagnostics; Thermo-Fisher Diagnostics FX Dr. Januzzi reports having received research grants and consulting income from Roche Diagnostics, Critical Diagnostics, Siemens Diagnostics, and Thermo-Fisher Diagnostics. NR 51 TC 31 Z9 34 U1 1 U2 4 PU ELSEVIER MASSON PI MILANO PA VIA PALEOCAPA 7, 20121 MILANO, ITALY SN 1875-2136 J9 ARCH CARDIOVASC DIS JI Arch. Cardiovasc. Dis. PD JAN PY 2012 VL 105 IS 1 BP 40 EP 50 DI 10.1016/j.acvd.2011.10.007 PG 11 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 921PW UT WOS:000302490500007 PM 22369917 ER PT J AU Manning, KJ Clarke, C Lorry, A Weintraub, D Wilkinson, JR Duda, JE Moberg, PJ AF Manning, Kevin J. Clarke, Christina Lorry, Alan Weintraub, Daniel Wilkinson, Jayne R. Duda, John E. Moberg, Paul J. TI Medication Management and Neuropsychological Performance in Parkinson's Disease SO CLINICAL NEUROPSYCHOLOGIST LA English DT Article DE Parkinson's disease; Medication management; Instrumental activities of daily living; Aging ID MILD COGNITIVE IMPAIRMENT; ADHERENCE; DEMENTIA; DIAGNOSIS; MOCA AB Medication non-adherence is associated with chronic disease and complex medication schedules, and Parkinson's disease (PD) patients also frequently have cognitive impairments that may interfere with effective medication management. The current study quantitatively assessed the medication management skills of PD patients and probed the neurocognitive underpinnings and clinical correlates of this skill. A total of 26 men with PD completed a neuropsychological battery and a modified version of the Hopkins Medication Schedule (HMS), a standard test of a person's ability to understand and implement a routine prescription medication. Estimated adherence rates from performance on the HMS were low. Memory, executive functioning, and processing speed were strongly related to different components of the HMS. A range of neuropsychological abilities is associated with the ability to understand and implement a medication schedule and pillbox in individuals with PD. C1 [Manning, Kevin J.] Drexel Univ, Dept Psychol, Philadelphia, PA 19104 USA. [Manning, Kevin J.; Weintraub, Daniel; Moberg, Paul J.] Univ Penn, Sch Med, Dept Psychiat, Philadelphia, PA 19104 USA. [Clarke, Christina] Ralph H Johnson Vet Affairs Med Ctr, Dept Pharm, Charleston, SC USA. [Lorry, Alan] Philadelphia Vet Affairs Med Ctr, Dept Pharm, Philadelphia, PA USA. [Lorry, Alan; Weintraub, Daniel; Wilkinson, Jayne R.; Duda, John E.; Moberg, Paul J.] Philadelphia Vet Affairs Med Ctr, Parkinsons Dis Res Educ & Clin Ctr, Philadelphia, PA USA. [Weintraub, Daniel; Wilkinson, Jayne R.; Duda, John E.; Moberg, Paul J.] Univ Penn, Sch Med, Dept Neurol, Philadelphia, PA 19104 USA. RP Manning, KJ (reprint author), Drexel Univ, Dept Psychol, PSA Bldg,3141 Chestnut St, Philadelphia, PA 19104 USA. EM kevin.j.manning@gmail.com FU NIMH NIH HHS [K23 MH067894] NR 31 TC 11 Z9 11 U1 1 U2 7 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1385-4046 J9 CLIN NEUROPSYCHOL JI Clin. Neuropsychol. PY 2012 VL 26 IS 1 BP 45 EP 58 DI 10.1080/13854046.2011.639312 PG 14 WC Psychology, Clinical; Clinical Neurology; Psychology SC Psychology; Neurosciences & Neurology GA 922JN UT WOS:000302543300005 PM 22150514 ER PT J AU Klein, MM Lee, JW Siegel, SM Downs, HM Oaklander, AL AF Klein, M. M. Lee, J. W. Siegel, S. M. Downs, H. M. Oaklander, A. L. TI Endoneurial pathology of the needlestick-nerve-injury model of Complex Regional Pain Syndrome, including rats with and without pain behaviors SO EUROPEAN JOURNAL OF PAIN LA English DT Article ID SYNDROME TYPE-I; MAST-CELLS; PERIPHERAL-NERVE; NEUROPATHIC PAIN; DIABETES-MELLITUS; SENSATION LIKE; SCIATIC-NERVE; SUBSTANCE-P; DISORDERS; NEURONS AB Current rodent models of neuropathic pain produce pain hypersensitivity in almost all lesioned animals and not all identified experimental effects are pain specific. 18G needlestick-nerve-injury (NNI) to one tibial nerve of outbred Sprague-Dawley rats models the phenotype of Complex Regional Pain Syndrome (CRPS), a post-traumatic neuropathic pain syndrome, leaving roughly half of NNI rats with hyperalgesia. We compared endoneurial data from these divergent endophenotypes searching for pathological changes specifically associated with pain-behaviors. Tibial, sural, and common sciatic nerves from 12 NNI rats plus 10 nerves from sham-operated controls were removed 14 days post-surgery for morphometric analysis. PGP9.5(+) unmyelinated-fibers were quantitated in plantar hindpaw skin. Distal tibial nerves of NNI rats had endoneurial edema, 30% fewer axons, twice as many mast cells, and thicker blood-vessel walls than uninjured tibial nerves. However the only significant difference between nerves from hyperalgesic versus non-hyperalgesic NNI rats was greater endoneurial edema in hyperalgesic rats (p < 0.01). We also discovered significant axonal losses in uninjured ipsilateral sural nerves of NNI rats, demonstrating spread of neuropathy to nearby nerves formerly thought spared. Tibial and sural nerves contralateral to NNI had significant changes in endoneurial blood-vessels. Similar pathological changes have been identified in CRPS-I patients. The current findings suggest that severity of endoneurial vasculopathy and inflammation may correlate better with neuropathic pain behaviors than degree of axonal loss. Spread of pathological changes to nearby ipsilateral and contralateral nerves might potentially contribute to extraterritorial pain in CRPS. C1 [Oaklander, A. L.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA 02114 USA. RP Oaklander, AL (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, 275 Charles St,Warren Bldg 310, Boston, MA 02114 USA. EM aoaklander@partners.org FU Public Health Service [NINDS NS42866, K24NS059892]; Reflex Sympathetic Dystrophy Association of America; National Organization for Rare Disorders FX Supported by the Public Health Service (NINDS NS42866, K24NS059892), the Reflex Sympathetic Dystrophy Association of America, and the National Organization for Rare Disorders. Presented in abstract form to the American Neurological Association and the Society for Neuroscience. This study does not concern commercial products and the authors have no conflicts of interest. NR 44 TC 3 Z9 3 U1 0 U2 7 PU WILEY PERIODICALS, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN STREET, MALDEN, MA 02148-529 USA SN 1090-3801 J9 EUR J PAIN JI Eur. J. Pain PD JAN PY 2012 VL 16 IS 1 BP 28 EP 37 DI 10.1016/j.ejpain.2011.05.004 PG 10 WC Anesthesiology; Clinical Neurology; Neurosciences SC Anesthesiology; Neurosciences & Neurology GA 921SG UT WOS:000302497200004 PM 21676634 ER PT J AU Skordis, N Efstathiou, E Kyriakides, TC Savvidou, A Savva, SC Phylactou, LA Shammas, C Neocleous, V AF Skordis, Nicos Efstathiou, Elisavet Kyriakides, Tassos C. Savvidou, Antria Savva, Savvas C. Phylactou, Leonidas A. Shammas, Christos Neocleous, Vassos TI Epidemiology of Type 1 diabetes mellitus in Cyprus: rising incidence at the dawn of the 21st century SO HORMONES-INTERNATIONAL JOURNAL OF ENDOCRINOLOGY AND METABOLISM LA English DT Article DE Epidemiology; Incidence; Type 1 Diabetes Mellitus ID ECOLOGICAL ANALYSIS; FINNISH CHILDREN; DRINKING-WATER; CHILDHOOD; WORLDWIDE; ONSET; RISK; DIAGNOSIS; NITRATE; TIME AB OBJECTIVE: The incidence of Type 1 diabetes mellitus (T1DM) in Greek-Cypriot children aged less than 15 years between 1990 and 2009 was examined along with gender differences concerning the age of onset and the seasonal variation at manifestation of the disease. DESIGN: All newly diagnosed cases of T1DM in children less than 15 years old were registered with the capture-recapture method from 1990 until 2009. RESULTS: The overall mean annual incidence during these 20 years is 12.46 per 100,000. A comparison of the incidence between the two decades (1990-1999 vs 2000-2009) indicated a rising trend, from 10.80 per 100,000 person-years during the first decade to 14.44 per 100,000 person-years during the second decade. There was an overall male predominance (M/F: 1.05), which is in agreement with the male predominance in the population less than 15 years of age, except for the group who manifested T1DM at ages 10-15 years where females prevail. The percentage of children who developed T1DM at ages 0-5 years in the total T1DM population increased in the second decade (26.4% vs 19.0%), and significantly more children were diagnosed during the cold months as opposed to the warm months (p < 0.001). CONCLUSION: The incidence of T1DM in Cyprus is rising. The identification of causative environmental factors will theoretically explain this phenomenon and new preventive strategies can therefore potentially be developed. C1 [Skordis, Nicos; Efstathiou, Elisavet; Savvidou, Antria] Makarios Hosp, Paediat Endocrine Unit, Dept Paediat, CY-1474 Nicosia, Cyprus. [Kyriakides, Tassos C.] Yale Univ, Yale Ctr Analyt Sci, Sch Publ Hlth, West Haven, CT USA. [Kyriakides, Tassos C.] US Dept Vet Affairs, VA Cooperat Studies Program Coordinating Ctr, West Haven, CT USA. [Savva, Savvas C.] Res & Educ Inst Child Hlth, Nicosia, Cyprus. [Phylactou, Leonidas A.; Shammas, Christos; Neocleous, Vassos] Cyprus Inst Neurol & Genet, Nicosia, Cyprus. RP Skordis, N (reprint author), Makarios Hosp, Paediat Endocrine Unit, Dept Paediat, CY-1474 Nicosia, Cyprus. EM nskordis@cytanet.com.cy NR 37 TC 6 Z9 6 U1 1 U2 6 PU HELLENIC ENDOCRINE SOC PI ATHENS PA 14 ALEXANDRAS AVE, ATHENS, 106 82, GREECE SN 1109-3099 J9 HORM-INT J ENDOCRINO JI Horm.-Int. J. Endocrinol. Metab. PD JAN-MAR PY 2012 VL 11 IS 1 BP 86 EP 93 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 921RN UT WOS:000302495100009 PM 22450348 ER PT J AU Scarcelli, G Pineda, R Yun, SH AF Scarcelli, Giuliano Pineda, Roberto Yun, Seok Hyun TI Brillouin Optical Microscopy for Corneal Biomechanics SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID OCULAR RESPONSE ANALYZER; COLLAGEN CROSS-LINKING; ULTRAVIOLET-A; REFRACTIVE-INDEX; IN-VIVO; IMAGING MICROSCOPY; ANTERIOR STROMA; PORCINE EYE; LENS; RIBOFLAVIN AB PURPOSE. The mechanical properties of corneal tissue are linked to prevalent ocular diseases and therapeutic procedures. Brillouin microscopy is a novel optical technology that enables three-dimensional mechanical imaging. In this study, the feasibility of this noncontact technique was tested for in situ quantitative assessment of the biomechanical properties of the cornea. METHODS. Brillouin light-scattering involves a spectral shift proportional to the longitudinal modulus of elasticity of the tissue. A 532-nm single-frequency laser and a custom-developed ultra-high-resolution spectrometer were used to measure the Brillouin frequency. Confocal scanning was used to perform Brillouin elasticity imaging of the corneas of whole bovine eyes. The longitudinal modulus of the bovine corneas was compared before and after riboflavin corneal collagen photo-cross-linking. The Brillouin measurements were then compared with conventional stress-strain mechanical test results. RESULTS. High-resolution Brillouin images of the cornea were obtained, revealing a striking depth-dependent variation of the elastic modulus across the cornea. Along the central axis, the Brillouin frequency shift varied gradually from 8.2 GHz in the epithelium to 7.5 GHz near the endothelium. The coefficients of the down slope were measured to be approximately 1.09, 0.32, and 2.94 GHz/mm in the anterior, posterior, and innermost stroma, respectively. On riboflavin collagen cross-linking, marked changes in the axial Brillouin profiles (P < 0.001) were noted before and after cross-linking. CONCLUSIONS. Brillouin imaging can assess the biomechanical properties of cornea in situ with high spatial resolution. This novel technique has the potential for use in clinical diagnostics and treatment monitoring. (Invest Ophthalmol Vis Sci. 2012;53:185-190) DOI:10.1167/iovs.11-8281 C1 [Scarcelli, Giuliano; Yun, Seok Hyun] Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02114 USA. [Scarcelli, Giuliano; Yun, Seok Hyun] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Pineda, Roberto] Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02114 USA. [Yun, Seok Hyun] Harvard MIT Hlth Sci & Technol, Cambridge, MA USA. RP Yun, SH (reprint author), Harvard Univ, Sch Med, Dept Dermatol, 55 Fruit St, Boston, MA 02114 USA. EM syun@hms.harvard.edu OI scarcelli, giuliano/0000-0002-1736-077X FU National Institutes of Health [R21EB008472]; National Science Foundation [CBET-0853773] FX Supported by a Tosteson Fellowship (GS), Grant R21EB008472 from the National Institutes of Health, and Grant CBET-0853773 from the National Science Foundation. NR 54 TC 76 Z9 77 U1 2 U2 26 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD JAN PY 2012 VL 53 IS 1 BP 185 EP 190 DI 10.1167/iovs.11-8281 PG 6 WC Ophthalmology SC Ophthalmology GA 924LY UT WOS:000302694500030 PM 22159012 ER PT J AU Adamus, G Brown, L Andrew, S Meza-Romero, R Burrows, GG Vandenbark, AA AF Adamus, Grazyna Brown, Lori Andrew, Shayne Meza-Romero, Roberto Burrows, Gregory G. Vandenbark, Arthur A. TI Neuroprotective Effects of Recombinant T-cell Receptor Ligand in Autoimmune Optic Neuritis in HLA-DR2 Mice SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID PROMISING THERAPEUTIC APPROACH; MULTIPLE-SCLEROSIS; TRANSGENIC MICE; TREATMENT TRIAL; FOLLOW-UP; ENCEPHALOMYELITIS; MYELIN; RISK; PEPTIDE; UVEITIS AB PURPOSE. Optic neuritis (ON) is a condition involving primary inflammation, demyelination, and axonal injury in the optic nerve and leads to apoptotic retinal ganglion cell (RGC) death, which contributes to the persistence of visual loss. Currently, ON has no effective treatment. The goal was to determine the effectiveness of immunotherapy with recombinant T-cell receptor ligand (RTL) in preventing ON in humanized HLA-DR2 transgenic mice. METHODS. Experimental autoimmune encephalomyelitis (EAE) was induced with myelin oligodendrocyte glycoprotein in humanized HLA-DR2 (DR beta 1* 1501) transgenic mice. Five consecutive doses of RTL342M were administrated at the onset of ON. The development of autoimmune ON was assessed by histopathology at different time points. The levels of myelin loss, axonal loss, and RGC damage were examined by immunofluorescence. RESULTS. HLA-DR2 mice developed chronic ON 2 days before EAE characterized by progressive neurodegeneration in both organs. RTL342M significantly suppressed inflammation in the optic nerve and spinal cord and provided protection for at least 30 days. Examination of myelin loss showed a marked suppression of demyelination and an increase in myelin recovery in the optic nerve. Moreover, RTL342M treatment revealed a neuroprotective effect on optic nerve axons and RGCs in retinas at postimmunization (PI) day 62. CONCLUSIONS. RTL342M suppressed clinical and histologic signs of EAE/ON by preventing the recruitment of inflammatory cells into the optic nerve and showed neuroprotective effects against ON. However, to achieve full therapeutic benefit, more doses may be needed. These findings suggest a possible clinical application of this novel class of T-cell-tolerizing drugs for patients with optic neuritis. (Invest Ophthalmol Vis Sci. 2012; 53: 406-412) DOI:10.1167/iovs.11-8419 C1 [Adamus, Grazyna; Brown, Lori] Oregon Hlth & Sci Univ, Casey Eye Inst, Portland, OR 97239 USA. [Vandenbark, Arthur A.] Dept Vet Affairs Med Ctr, Res Serv, Portland, OR USA. [Andrew, Shayne; Meza-Romero, Roberto; Burrows, Gregory G.] Portland VA Med Ctr, R&D31, Portland, OR USA. [Burrows, Gregory G.] Oregon Hlth & Sci Univ, Dept Biochem, Portland, OR 97239 USA. [Burrows, Gregory G.; Vandenbark, Arthur A.] Oregon Hlth & Sci Univ, Dept Neurol, Portland, OR 97239 USA. [Vandenbark, Arthur A.] Oregon Hlth & Sci Univ, Dept Mol Microbiol & Immunol, Portland, OR 97239 USA. RP Adamus, G (reprint author), Oregon Hlth & Sci Univ, Casey Eye Inst, BRB L467AD,3181 SW Sam Jackson Pk Rd, Portland, OR 97239 USA. EM adamusg@ohsu.edu FU National Eye Institute [EY17781]; National Institutes of Health [NIH NS047661]; Research to Prevent Blindness; Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Biomedical Laboratory Research and Development FX Supported by National Eye Institute Grant EY17781 (GA) and National Institutes of Health Grant NIH NS047661 (AAV) and an unrestricted grant from Research to Prevent Blindness (CEI). This material is based on work supported in part by the Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Biomedical Laboratory Research and Development. The contents do not represent the views of the Department of Veterans Affairs or the United States Government. NR 36 TC 6 Z9 6 U1 0 U2 1 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD JAN PY 2012 VL 53 IS 1 BP 406 EP 412 DI 10.1167/iovs.11-8419 PG 7 WC Ophthalmology SC Ophthalmology GA 924LY UT WOS:000302694500059 PM 22167100 ER PT J AU Park, WM Wang, S Kim, YH Wood, KB Sim, JA Li, G AF Park, W. M. Wang, S. Kim, Y. H. Wood, K. B. Sim, J. A. Li, G. TI Effect of the Intra-Abdominal Pressure and the Center of Segmental Body Mass on the Lumbar Spine Mechanics - A Computational Parametric Study SO JOURNAL OF BIOMECHANICAL ENGINEERING-TRANSACTIONS OF THE ASME LA English DT Article DE spine biomechanics; lumbar spine; intra-abdominal pressure; center of mass ID IN-VIVO; MUSCLE FORCES; FOLLOWER LOAD; GEOMETRICAL DIMENSIONS; FIXATION DEVICE; TRUNK; EXTENSION; MODEL; ACTIVATION; VERTEBRAE AB Determination of physiological loads in human lumbar spine is critical for understanding the mechanisms of lumbar diseases and for designing surgical treatments. Computational models have been used widely to estimate the physiological loads of the spine during simulated functional activities. However, various assumptions on physiological factors such as the intra-abdominal pressure (IAP), centers of mass (COMs) of the upper body and lumbar segments, and vertebral centers of rotation (CORs) have been made in modeling techniques. Systematic knowledge of how these assumptions will affect the predicted spinal biomechanics is important for improving the simulation accuracy. In this paper, we developed a 3D subject-specific numerical model of the lumbosacral spine including T12 and 90 muscles. The effects of the IAP magnitude and COMs locations on the COR of each motion segment and on the joint/muscle forces were investigated using a global convergence optimization procedure when the subject was in a weight bearing standing position. The data indicated that the line connecting the CORs showed a smaller curvature than the lordosis of the lumbar spine in standing posture when the IAP was 0 kPa and the COMs were 10 mm anterior to the geometric center of the T12 vertebra. Increasing the IAP from 0 kPa to 10 kPa shifted the location of CORs toward the posterior direction (from 1.4+/-8.9 mm anterior to intervertebral disc (IVD) centers to 40.5+/-3.1 mm posterior to the IVD centers) and reduced the average joint force (from 0.78+/-0.11 Body weight (BW) to 0.31+/-0.07 BW) and overall muscle force (from 349.3+/-57.7 N to 221.5+/-84.2 N). Anterior movement of the COMs from 30 mm to 70 mm relative to the geometric center of T12 vertebra caused an anterior shift of the CORs (from 25.1+/-8.3 mm posterior to IVD centers to 7.8+/-6.2 mm anterior to IVD centers) and increases of average joint forces (from 0.78+/-0.1 BW to 0.93+/-0.1 BW) and muscle force (from 348.9+/-47.7 N to 452.9+/-58.6 N). Therefore, it is important to consider the IAP and correct COMs in order to accurately simulate human spine biomechanics. The method and results of this study could be useful for designing prevention strategies of spinal injuries and recurrences, and for enhancing rehabilitation efficiency. [DOI: 10.1115/1.4005541] C1 [Park, W. M.; Wang, S.; Sim, J. A.; Li, G.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Bioengn Lab,Dept Orthopaed Surg, Boston, MA 02114 USA. [Park, W. M.; Kim, Y. H.] Kyung Hee Univ, Dept Mech Engn, Yongin, Gyeonggi Do, South Korea. [Wang, S.] MIT, Dept Mech Engn, Cambridge, MA 02139 USA. [Wood, K. B.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Spine Serv,Dept Orthopaed Surg, Boston, MA 02114 USA. [Sim, J. A.] Gachon Univ, Gachon Med Sch, Gil Med Ctr, Dept Orthopaed Surg, Inchon, South Korea. RP Li, G (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Bioengn Lab,Dept Orthopaed Surg, 55 Fruit St,GRJ 1215, Boston, MA 02114 USA. EM muhaguy@gmail.com; SWANG17@partners.org; yoonhkim@khu.ac.kr; kbwood@partners.org; sim_ja@gilhospital.com; gli1@partners.org FU ECOR from MGH; NIH [R21AR057989]; National Agenda Project (NAP); Korea Research Council of Fundamental Science Technology [P-09-JC-LU63-C01] FX This work is supported by ECOR fund from MGH and NIH (Grant No. R21AR057989), and National Agenda Project (NAP) funded by Korea Research Council of Fundamental Science & Technology (Grant No. P-09-JC-LU63-C01). NR 48 TC 8 Z9 8 U1 5 U2 15 PU ASME-AMER SOC MECHANICAL ENG PI NEW YORK PA THREE PARK AVE, NEW YORK, NY 10016-5990 USA SN 0148-0731 J9 J BIOMECH ENG-T ASME JI J. Biomech. Eng.-Trans. ASME PD JAN PY 2012 VL 134 IS 1 AR 011009 DI 10.1115/1.4005541 PG 10 WC Biophysics; Engineering, Biomedical SC Biophysics; Engineering GA 922XO UT WOS:000302582100009 PM 22482664 ER PT J AU Larvie, M Shoup, T Chang, WC Chigweshe, L Hartshorn, K White, MR Stahl, GL Elmaleh, DR Takahashi, K AF Larvie, Mykol Shoup, Timothy Chang, Wei-Chuan Chigweshe, Lorencia Hartshorn, Kevan White, Mitchell R. Stahl, Gregory L. Elmaleh, David R. Takahashi, Kazue TI Mannose-Binding Lectin Binds to Amyloid beta Protein and Modulates Inflammation SO JOURNAL OF BIOMEDICINE AND BIOTECHNOLOGY LA English DT Article ID INFLUENZA-A VIRUS; PATTERN-RECOGNITION MOLECULE; AGE-DEPENDENT ASSOCIATION; CYSTEINE-RICH DOMAIN; ALZHEIMERS-DISEASE; INCREASES SUSCEPTIBILITY; INNATE IMMUNITY; GENETIC-VARIANTS; EPITHELIAL-CELLS; DEFICIENT MICE AB Mannose-binding lectin (MBL), a soluble factor of the innate immune system, is a pattern recognition molecule with a number of known ligands, including viruses, bacteria, and molecules from abnormal self tissues. In addition to its role in immunity, MBL also functions in the maintenance of tissue homeostasis. We present evidence here that MBL binds to amyloid beta peptides. MBL binding to other known carbohydrate ligands is calcium-dependent and has been attributed to the carbohydrate-recognition domain, a common feature of other C-type lectins. In contrast, we find that the features of MBL binding to A beta are more similar to the reported binding characteristics of the cysteine-rich domain of the unrelated mannose receptor and therefore may involve the MBL cysteine-rich domain. Differences in MBL ligand binding may contribute to modulation of inflammatory response and may correlate with the function of MBL in processes such as coagulation and tissue homeostasis. C1 [Chang, Wei-Chuan; Chigweshe, Lorencia; Takahashi, Kazue] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pediat, Boston, MA 02114 USA. [Larvie, Mykol] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Neuroradiol,Dept Radiol, Boston, MA 02114 USA. [Larvie, Mykol; Shoup, Timothy; Elmaleh, David R.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Nucl Med & Mol Imaging,Dept Radiol, Boston, MA 02114 USA. [Hartshorn, Kevan; White, Mitchell R.] Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA. [Stahl, Gregory L.] Harvard Univ, Sch Med, Dept Anesthesiol Perioperat & Pain Med, Ctr Expt Therapeut & Reperfus Injury,Harvard Inst, Boston, MA 02115 USA. RP Takahashi, K (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pediat, Boston, MA 02114 USA. EM ktakahashi1@partners.org FU NIH [U01 AI074503] FX This paper was supported in part by grants from NIH U01 AI074503. The authors thank Enzon Pharmaceutical Inc. for recombinant human MBL. NR 70 TC 8 Z9 8 U1 0 U2 1 PU HINDAWI PUBLISHING CORPORATION PI NEW YORK PA 410 PARK AVENUE, 15TH FLOOR, #287 PMB, NEW YORK, NY 10022 USA SN 1110-7243 J9 J BIOMED BIOTECHNOL JI J. Biomed. Biotechnol. PY 2012 AR 929803 DI 10.1155/2012/929803 PG 12 WC Biotechnology & Applied Microbiology; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Research & Experimental Medicine GA 924JQ UT WOS:000302688000001 ER PT J AU Jeon, JY Meyerhardt, JA AF Jeon, Justin Y. Meyerhardt, Jeffrey A. TI Energy in and Energy out: What Matters for Survivors of Colorectal Cancer? SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Editorial Material ID BODY-MASS INDEX; III COLON-CANCER; TREATMENT-RELATED TOXICITY; PHYSICAL-ACTIVITY; RECTAL-CANCER; INSULIN-RESISTANCE; PATIENT SURVIVAL; ADIPOSE-TISSUE; RISK; OBESITY C1 [Jeon, Justin Y.] Yonsei Univ, Seoul 120749, South Korea. [Meyerhardt, Jeffrey A.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Jeon, JY (reprint author), Yonsei Univ, Seoul 120749, South Korea. FU NCI NIH HHS [R01 CA149222] NR 46 TC 10 Z9 10 U1 0 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JAN 1 PY 2012 VL 30 IS 1 BP 7 EP 10 DI 10.1200/JCO.2011.39.6374 PG 5 WC Oncology SC Oncology GA 923KJ UT WOS:000302617900007 PM 22124098 ER PT J AU Rahbari, NN Bork, U Motschall, E Thorlund, K Buchler, MW Koch, M Weitz, J AF Rahbari, Nuh N. Bork, Ulrich Motschall, Edith Thorlund, Kristian Buechler, Markus W. Koch, Moritz Weitz, Juergen TI Molecular Detection of Tumor Cells in Regional Lymph Nodes Is Associated With Disease Recurrence and Poor Survival in Node-Negative Colorectal Cancer: A Systematic Review and Meta-Analysis SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID II COLON-CANCER; POLYMERASE-CHAIN-REACTION; LOWER RECTAL-CANCER; GUANYLYL CYCLASE-C; PROGNOSTIC-SIGNIFICANCE; STAGE-I; CLINICAL-SIGNIFICANCE; CURATIVE RESECTION; BETA-CATENIN; DUKES STAGES AB Purpose Up to 25% of patients with node-negative colorectal cancer (CRC) on conventional histopathologic analysis ultimately die of recurrent disease. We performed a systematic review with meta-analyses to clarify whether molecular detection of isolated tumor cells or micrometastases in regional lymph nodes indicates high risk of disease recurrence and poor survival in node-negative CRC. Methods The following databases were searched in August 2011 to identify studies on the prognostic significance of molecular tumor-cell detection in regional lymph nodes of node-negative CRC: MEDLINE, BIOSIS, Science Citation Index, EMBASE, CCMed, and publisher databases. We extracted hazard ratios (HRs) and associated 95% CIs from the identified studies and performed random-effects model meta-analyses on overall survival, disease-specific survival, and disease-free survival. Results A total of 39 studies with a cumulative sample size of 4,087 patients were included. Immunohistochemistry, reverse transcriptase polymerase chain reaction, and both techniques were applied in 30, seven, and two studies, respectively. Thirteen studies were graded with low risk of bias. Meta-analyses revealed that molecular tumor-cell detection in regional lymph nodes was associated with poor overall survival (HR, 2.20; 95% CI, 1.43 to 3.40), disease-specific survival (HR, 3.37; 95% CI, 2.31 to 4.93), and disease-free survival (HR, 2.24; 95% CI, 1.57-3.20). Subgroup analyses showed the prognostic significance of molecular tumor-cell detection of being independent of the applied detection method, molecular target, and number of retrieved lymph nodes. Conclusion Molecular detection of occult disease in regional lymph nodes is associated with an increased risk of disease recurrence and poor survival in patients with node-negative CRC. J Clin Oncol 30:60-70. (c) 2011 by American Society of Clinical Oncology C1 [Rahbari, Nuh N.] Heidelberg Univ, Dept Gen Visceral & Transplant Surg, D-69120 Heidelberg, Germany. [Motschall, Edith] Univ Freiburg, D-79106 Freiburg, Germany. [Rahbari, Nuh N.] Massachusetts Gen Hosp, Edwin L Steele Lab Tumor Biol, Boston, MA 02114 USA. [Rahbari, Nuh N.] Harvard Univ, Sch Med, Boston, MA USA. [Thorlund, Kristian] McMaster Univ, Hamilton, ON, Canada. RP Rahbari, NN (reprint author), Heidelberg Univ, Dept Gen Visceral & Transplant Surg, Neuenheimer Feld 110, D-69120 Heidelberg, Germany. EM nuh.rahbari@med.uni-heidelberg.de OI Motschall, Edith/0000-0001-7795-242X FU Deutsche Forschungsgemeinschaft [WE 3548/4-1] FX Supported by the Deutsche Forschungsgemeinschaft (Grant No. WE 3548/4-1). NR 82 TC 66 Z9 71 U1 0 U2 8 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JAN 1 PY 2012 VL 30 IS 1 BP 60 EP 70 DI 10.1200/JCO.2011.36.9504 PG 11 WC Oncology SC Oncology GA 923KJ UT WOS:000302617900014 PM 22124103 ER PT J AU Chawla, SP Staddon, AP Baker, LH Schuetze, SM Tolcher, AW D'Amato, GZ Blay, JY Mita, MM Sankhala, KK Berk, L Rivera, VM Clackson, T Loewy, JW Haluska, FG Demetri, GD AF Chawla, Sant P. Staddon, Arthur P. Baker, Laurence H. Schuetze, Scott M. Tolcher, Anthony W. D'Amato, Gina Z. Blay, Jean-Yves Mita, Monica M. Sankhala, Kamalesh K. Berk, Lori Rivera, Victor M. Clackson, Tim Loewy, John W. Haluska, Frank G. Demetri, George D. TI Phase II Study of the Mammalian Target of Rapamycin Inhibitor Ridaforolimus in Patients With Advanced Bone and Soft Tissue Sarcomas SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID GASTROINTESTINAL STROMAL TUMORS; ANGIOGENESIS INHIBITOR; EUROPEAN-ORGANIZATION; TRIAL; EFFICACY; ECTEINASCIDIN-743; CHEMOTHERAPY; TRABECTEDIN; IMATINIB; MK-8669 AB Purpose Ridaforolimus is an inhibitor of mammalian target of rapamycin, an integral component of the phosphatidyl 3-kinase/AKT signaling pathway, with early evidence of activity in sarcomas. This multicenter, open-label, single-arm, phase II trial was conducted to assess the antitumor activity of ridaforolimus in patients with distinct subtypes of advanced sarcomas. Patients and Methods Patients with metastatic or unresectable soft tissue or bone sarcomas received ridaforolimus 12.5 mg administered as a 30-minute intravenous infusion once daily for 5 days every 2 weeks. The primary end point was clinical benefit response (CBR) rate (complete response or partial response [PR] or stable disease >= 16 weeks). Safety, progression-free survival (PFS), overall survival (OS), time to progression, and duration of response were also evaluated. Results A total of 212 patients were treated in four separate histologic cohorts. In this heavily pretreated population, 61 patients (28.8%) achieved CBR. Median PFS was 15.3 weeks; median OS was 40 weeks. Response Evaluation Criteria in Solid Tumors (RECIST) confirmed response rate was 1.9%, with four patients achieving confirmed PR (two with osteosarcoma, one with spindle cell sarcoma, and one with malignant fibrous histiocytoma). Archival tumor protein markers analyzed were not correlated with CBR. Related adverse events were generally mild or moderate and consisted primarily of stomatitis, mucosal inflammation, mouth ulceration, rash, and fatigue. Conclusion Single-agent ridaforolimus in patients with advanced and pretreated sarcomas led to PFS results that compare favorably with historical metrics. A phase III trial based on these data will further define ridaforolimus activity in sarcomas. J Clin Oncol 30:78-84. (c) 2011 by American Society of Clinical Oncology C1 [Demetri, George D.] Dana Farber Canc Inst, Ludwig Ctr, Boston, MA 02215 USA. [Demetri, George D.] Harvard Univ, Sch Med, Boston, MA USA. [Chawla, Sant P.] Sarcoma Oncol Ctr, Int Inst Clin Studies, Santa Monica, CA USA. [Staddon, Arthur P.] Penn Oncol Hematol Associates, Philadelphia, PA USA. [Baker, Laurence H.; Schuetze, Scott M.] Univ Michigan, Sch Med, Ann Arbor, MI USA. [Tolcher, Anthony W.] S Texas Accelerated Res Therapeut, San Antonio, TX USA. [Mita, Monica M.; Sankhala, Kamalesh K.] Inst Drug Dev, Canc Therapy Res Ctr, San Antonio, TX USA. [D'Amato, Gina Z.] Univ S Florida, H Lee Moffitt Canc Ctr, Tampa, FL 33682 USA. [Blay, Jean-Yves] Ctr Leon Berard, F-69373 Lyon, France. RP Demetri, GD (reprint author), Dana Farber Canc Inst, Ludwig Ctr, Dana 1212,450 Brookline Ave, Boston, MA 02215 USA. EM gdemetri@partners.org RI Blay, Jean-Yves/N-3966-2016 OI Blay, Jean-Yves/0000-0001-7190-120X FU ARIAD Pharmaceuticals, Cambridge, MA; ARIAD Pharmaceuticals; Merck; Amgen; GlaxoSmithKline; sanofi-aventis; Novartis; Pfizer; Johnson Johnson; PharmaMar FX Supported by ARIAD Pharmaceuticals, Cambridge, MA.. Research Funding: Sant P. Chawla, ARIAD Pharmaceuticals; Arthur P. Staddon, ARIAD Pharmaceuticals, Merck, Amgen, GlaxoSmithKline, sanofi-aventis; Scott M. Schuetze, ARIAD Pharmaceuticals; Anthony W. Tolcher, ARIAD Pharmaceuticals; Monica M. Mita, ARIAD Pharmaceuticals; Kamalesh K. Sankhala, ARIAD Pharmaceuticals; George D. Demetri, ARIAD Pharmaceuticals, Merck, Novartis, Pfizer, Amgen, GlaxoSmithKline, Johnson & Johnson, PharmaMar NR 34 TC 101 Z9 108 U1 0 U2 6 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JAN 1 PY 2012 VL 30 IS 1 BP 78 EP 84 DI 10.1200/JCO.2011.35.6329 PG 7 WC Oncology SC Oncology GA 923KJ UT WOS:000302617900016 PM 22067397 ER PT J AU Oxnard, GR Schwartz, LH Riely, GJ AF Oxnard, Geoffrey R. Schwartz, Lawrence H. Riely, Gregory J. TI Radiologic Reviews: More Second Guessing From Armchairs Cannot Lead the Way Reply SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Letter ID TUMOR MEASUREMENTS; VARIABILITY; SCANS C1 [Oxnard, Geoffrey R.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Schwartz, Lawrence H.] Columbia Univ Coll Phys & Surg, New York, NY 10032 USA. [Riely, Gregory J.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. RP Oxnard, GR (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. NR 5 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JAN 1 PY 2012 VL 30 IS 1 BP 117 EP 117 DI 10.1200/JCO.2011.39.3959 PG 1 WC Oncology SC Oncology GA 923KJ UT WOS:000302617900025 ER PT J AU Rowles, J Duan, CM AF Rowles, Joanna Duan, Changming TI Perceived Racism and Encouragement Among African American Adults SO JOURNAL OF MULTICULTURAL COUNSELING AND DEVELOPMENT LA English DT Article ID MENTAL-HEALTH; DISCRIMINATION; SOCIALIZATION; EXPERIENCES; IDENTITY AB The effects of spirituality, racial socialization, and ethnic pride on encouragement in the face of racism among African American adults (N = 201) were investigated. The negative relationship between perceived racism and encouragement disappeared when spirituality, ethnic pride, and a racial socialization history were entered into the regression equation. C1 [Rowles, Joanna] Greater Los Angeles Vet Adm Healthcare Syst, Los Angeles, CA 90073 USA. [Duan, Changming] Univ Kansas, Dept Psychol & Res Educ, Lawrence, KS 66045 USA. RP Rowles, J (reprint author), Greater Los Angeles Vet Adm Healthcare Syst, 11301 Wilshire Blvd,Bldg 206, Los Angeles, CA 90073 USA. EM Joanna.rowles@va.gov NR 20 TC 3 Z9 3 U1 1 U2 1 PU WILEY PERIODICALS, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN STREET, MALDEN, MA 02148-529 USA SN 0883-8534 J9 J MULTICULT COUNS D JI J. Multicult. Couns. Dev. PD JAN PY 2012 VL 40 IS 1 BP 11 EP 23 DI 10.1111/j.2161-1912.2012.00002.x PG 13 WC Psychology, Applied SC Psychology GA 922LF UT WOS:000302547800002 ER PT J AU Wu, FY Selvadurai, C Smithwick, Q Cain, J Cavallerano, J Silver, P Goldring, E AF Wu, Faye Selvadurai, Chindhuri Smithwick, Quinn Cain, James Cavallerano, Jerry Silver, Phil Goldring, Elizabeth TI The Seeing Machine Camera: An Artistic Tool for the Visually Challenged Conceived by a Visually Challenged Artist SO LEONARDO LA English DT Article AB The Vision Group at the Center for Advanced Visual Studies (CAVS) at the Massachusetts Institute of Technology (MIT) has developed the Seeing Machine Camera (SMC) under the direction of Elizabeth Goldring, a visually challenged artist. The SMC is an innovative tool that enables artistic expression for those with decreased vision. The camera enhances the ability to see the face of a loved one, look at a painting in a museum, photograph landscapes or create digital artwork. For visually challenged artists who may feel isolated from their visual world, the SMC provides an opportunity to connect to the people around them, enjoy a greater sense of independence and expand their creativity. C1 [Wu, Faye] Robust Design Grp, Cambridge, MA 02139 USA. [Selvadurai, Chindhuri] Manoach Lab, Charlestown, MA 02129 USA. [Smithwick, Quinn] MIT Media Lab, Cambridge, MA 02139 USA. [Cain, James] MIT, Off Educ Innovat & Technol, Cambridge, MA 02139 USA. [Cavallerano, Jerry; Silver, Phil] Joslin Diabet Ctr, William Beetham Eye Unit, Boston, MA 02215 USA. [Goldring, Elizabeth] MIT Program Art Culture & Technol, Cambridge, MA 02139 USA. RP Wu, FY (reprint author), Robust Design Grp, 77 Massachusetts Ave,3-436, Cambridge, MA 02139 USA. EM yfwu@mit.edu; chindhuri@gmail.com; smithwic@alum.mit.edu; jrcain@mit.edu; jerry.cavallerano@joslin.harvard.edu; philip.silver@joslin.harvard.edu; goldring@mit.edu NR 5 TC 0 Z9 0 U1 0 U2 0 PU MIT PRESS PI CAMBRIDGE PA 55 HAYWARD STREET, CAMBRIDGE, MA 02142 USA SN 0024-094X J9 LEONARDO JI Leonardo PY 2012 VL 45 IS 2 BP 141 EP 147 PG 7 WC Art SC Art GA 910CV UT WOS:000301615700006 ER PT S AU Huang, YY Tedford, CE McCarthy, T Hamblin, MR AF Huang, Ying-Ying Tedford, Clark E. McCarthy, Thomas Hamblin, Michael R. BE Hamblin, MR Anders, J Carroll, JD TI Low level laser therapy reduces oxidative stress in cortical neurons in vitro SO MECHANISMS FOR LOW-LIGHT THERAPY VII SE Proceedings of SPIE LA English DT Proceedings Paper CT Conference on Mechanisms for Low-Light Therapy VII CY JAN 21, 2012 CL San Francisco, CA SP SPIE DE low-level laser therapy; cultured cortical neurons; oxidative stress; reactive oxygen species; cobalt chloride; hydrogen peroxide ID TERM NEUROLOGICAL DEFICITS; NEAR-INFRARED LIGHT; HELIUM-NEON LASER; PROMOTES REGENERATION; FUNCTIONAL RECOVERY; ISCHEMIC-STROKE; SPINAL-CORD; IRRADIATION; MITOCHONDRIA; CELLS AB It is accepted that the mechanisms of low level laser therapy (LLLT) involves photons that are absorbed in the mitochondria of cells and lead to increase of mitochondrial metabolism resulting in more electron transport, increase of mitochondrial membrane potential, and more ATP production. Intracellular calcium changes are seen that correlate with mitochondrial stimulation. The situation with two other intermediates is more complex however: reactive oxygen species (ROS) and nitric oxide (NO). Evidence exists that low levels of ROS are produced by LLLT in normal cells that can be beneficial by (for instance) activating NF-kB. However high fluences of light can produce large amounts of ROS that can damage the cells. In oxidatively stressed cells the situation may be different. We exposed primary cultured cortical neurons to hydrogen peroxide (H2O2) or cobalt chloride (CoCl2) oxidative insults in the presence or absence of LLLT (810-nm laser at 0.3 or 3 J/cm(2)). Cell viability of cortical neurons was determined by lactate dehydrogenase assay. ROS in neurons was detected using an ROS probe, MitoRox with confocal microscopy. Results showed that LLLT dose-dependently reversed ROS production and protected cortical neurons against H2O2 or CoCl2 induced oxidative injury in cultured cortical neurons. Conclusion: LLLT can protect cortical neurons against oxidative stress by reversing the levels of ROS. C1 [Huang, Ying-Ying; Hamblin, Michael R.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 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; hamblin@helix.mgh.harvard.edu OI Hamblin, Michael/0000-0001-6431-4605 NR 43 TC 0 Z9 0 U1 0 U2 3 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-0-8194-8854-1 J9 PROC SPIE PY 2012 VL 8211 AR 821103 DI 10.1117/12.912948 PG 8 WC Optics SC Optics GA BZR70 UT WOS:000302602400001 ER PT S AU Xuan, WJ Wu, QH Huang, YY Ando, T Huang, L Hamblin, MR AF Xuan, Weijun Wu, Qiuhe Huang, Ying-Ying Ando, Takahiro Huang, Liyi Hamblin, Michael R. BE Hamblin, MR Anders, J Carroll, JD TI In vivo studies of low level laser (light) therapy for traumatic brain injury SO MECHANISMS FOR LOW-LIGHT THERAPY VII SE Proceedings of SPIE LA English DT Proceedings Paper CT Conference on Mechanisms for Low-Light Therapy VII CY JAN 21, 2012 CL San Francisco, CA SP SPIE DE low-level laser therapy; traumatic brain injury; controlled cortical impact; mouse model; neurological severity score; wire grip and motion test ID TERM NEUROLOGICAL DEFICITS; ACUTE ISCHEMIC-STROKE; FLUORO-JADE; ADULT BRAIN; NEURONAL DEGENERATION; SUBVENTRICULAR ZONE; TRANSCRANIAL LASER; DOSE-RESPONSE; STEM-CELLS; MICE AB Low-level laser (or light) therapy (LLLT) is attracting growing interest to treat both stroke and traumatic brain injury (TBI). The fact that near-infrared light can penetrate into the brain allows non-invasive treatment to be carried out with a low likelihood of treatment-related adverse events. It is proposed that red and NIR light is absorbed by chromophores in the mitochondria of cells leading to changes in gene transcription and upregulation of proteins involved in cell survival, antioxidant production, collagen synthesis, reduction of chronic inflammation and cell migration and proliferation. We developed a mouse model of controlled cortical impact (CCI) TBI and examined the effect of 0, 1, 3, and 14 daily 810-nm CW laser treatments in the CCI model as measured by neurological severity score and wire grip and motion test. 1 laser Tx gave a significant improvement while 3 laser Tx was even better. Surprisingly 14 laser Tx was no better than no treatment. Histological studies at necropsy suggested that the neurodegeneration was reduced at 14 days and that the cortical lesion was repaired by BrdU+ve neural progenitor (stem) cells at 28 days. Transcranial laser therapy is a promising treatment for acute (and chronic TBI) and the lack of side-effects and paucity of alternative treatments encourages early clinical trials. C1 [Xuan, Weijun; Wu, Qiuhe; Huang, Ying-Ying; Ando, Takahiro; Huang, Liyi; Hamblin, Michael R.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 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; hamblin@helix.mgh.harvard.edu OI Hamblin, Michael/0000-0001-6431-4605 NR 52 TC 0 Z9 0 U1 0 U2 4 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-0-8194-8854-1 J9 PROC SPIE PY 2012 VL 8211 AR 82110A DI 10.1117/12.905782 PG 10 WC Optics SC Optics GA BZR70 UT WOS:000302602400007 ER PT J AU Kohli, P Cannon, CP AF Kohli, Payal Cannon, Christopher P. TI Triglycerides: How Much Credit Do They Deserve? SO MEDICAL CLINICS OF NORTH AMERICA LA English DT Article DE Hypertriglyceridemia; Dyslipidemia; Statin; Metabolic syndrome; Diabetes ID CORONARY-HEART-DISEASE; DENSITY-LIPOPROTEIN-CHOLESTEROL; TYPE-2 DIABETES-MELLITUS; METABOLIC RISK-FACTORS; CARDIOVASCULAR-DISEASE; MYOCARDIAL-INFARCTION; SECONDARY PREVENTION; CONTROLLED-TRIAL; LDL CHOLESTEROL; WEIGHT-LOSS AB In the modern era of statin therapy, major advances have been made in treating coronary heart disease. However, despite intensive treatment with statin therapy, residual cardiovascular risk persists and has been attributed to the persistence of atherogenic dyslipidemia and, in part, elevated triglycerides (TGs). In this review, the authors focus on the mechanism of elevated TGs and provide a discussion of the challenges of measuring TGs as a biomarker, its role in the pathogenesis of atherosclerotic heart disease, and results of several recent studies that have elucidated the relationship between TGs and cardiovascular morbidity and mortality. C1 [Kohli, Payal; Cannon, Christopher P.] Brigham & Womens Hosp, Dept Med, Div Cardiovasc, TIMI Study Grp, Boston, MA 02115 USA. RP Kohli, P (reprint author), Brigham & Womens Hosp, Dept Med, Div Cardiovasc, TIMI Study Grp, 350 Longwood Ave,1st Floor, Boston, MA 02115 USA. EM pkohli@partners.org NR 91 TC 9 Z9 9 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 0025-7125 J9 MED CLIN N AM JI Med. Clin. N. Am. PD JAN PY 2012 VL 96 IS 1 BP 39 EP + DI 10.1016/j.mcna.2011.11.006 PG 19 WC Medicine, General & Internal SC General & Internal Medicine GA 926HZ UT WOS:000302823200005 PM 22391250 ER PT S AU Srinivasan, VJ Radhakrishnan, H Jiang, JY Barry, S Cable, AE AF Srinivasan, Vivek J. Radhakrishnan, Harsha Jiang, James Y. Barry, Scott Cable, Alex E. BE Izatt, JA Fujimoto, JG Tuchin, VV TI Optical Coherence Microscopy for deep tissue imaging of the cerebral cortex with intrinsic contrast SO OPTICAL COHERENCE TOMOGRAPHY AND COHERENCE DOMAIN OPTICAL METHODS IN BIOMEDICINE XVI SE Proceedings of SPIE LA English DT Proceedings Paper CT Conference on Optical Coherence Tomography and Coherence Domain Optical Methods in Biomedicine XVI/SPIE Photonics West Symposia CY JAN 23-25, 2012 CL San Francisco, CA SP SPIE DE Optical Coherence Tomography; angiography; Optical Coherence Microscopy; neuron; myelin; scattering; hemodynamics; image processing ID 2-PHOTON; EXCITATION AB We demonstrate Optical Coherence Microscopy (OCM) for in vivo imaging of the rat cerebral cortex. Imaging does not require addition of dyes or contrast agents, and is achieved through intrinsic scattering contrast and image processing alone. Furthermore, we demonstrate in vivo, quantitative measurements of optical properties and angiography in the rat cerebral cortex. Imaging depths greater than those achieved by conventional two-photon microscopy are demonstrated. C1 [Srinivasan, Vivek J.; Radhakrishnan, Harsha] Harvard Univ, Sch Med, Massachusetts Gen Hosp,Dept Radiol, MGH MIT HMS Athinoula A Martinos Ctr Biomed Imagi, Charlestown, MA 02129 USA. RP Srinivasan, VJ (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp,Dept Radiol, MGH MIT HMS Athinoula A Martinos Ctr Biomed Imagi, Charlestown, MA 02129 USA. NR 8 TC 0 Z9 0 U1 0 U2 0 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-0-8194-8856-5 J9 PROC SPIE PY 2012 VL 8213 AR 82131Y DI 10.1117/12.911587 PG 5 WC Optics; Radiology, Nuclear Medicine & Medical Imaging SC Optics; Radiology, Nuclear Medicine & Medical Imaging GA BZR71 UT WOS:000302605000034 ER PT J AU Lipinski, B Pretorius, E AF Lipinski, Boguslaw Pretorius, Etheresia TI Novel pathway of iron-induced blood coagulation: implications for diabetes mellitus and its complications SO POLSKIE ARCHIWUM MEDYCYNY WEWNETRZNEJ-POLISH ARCHIVES OF INTERNAL MEDICINE LA English DT Review DE diabetes; fibrinogen; hydroxyl radicals; iron; polyphenols ID OXIDATIVE STRESS; METABOLIC SYNDROME; ERYTHROCYTE SEDIMENTATION; INSULIN-RESISTANCE; GLYCEMIC CONTROL; HEART-DISEASE; LABILE IRON; LIPOIC ACID; IN-VITRO; FIBRIN AB Fibrinogen (FBG) is a high-molecular-weight protein and precursor to the enzymatically formed fibrin. It has been recently discovered that FBG can be converted into an insoluble, fibrin-like polymer by a nonenzymatic action of hydroxyl radicals (HRs). These free radicals are generated due to the reaction between hydroxyl groups of water and trivalent ferric ions without the participation of any redox agent. The inter-action between HRs and FBG occurs in a purified system, as well as in human plasma and in whole blood. Scanning electron microscopy (SEM) of thrombin-induced fibers and those generated with ferric chloride has shown substantial differences in their morphology and susceptibility to enzymatic degradation. Fibrin strands caused by thrombin are thick and easily digested with chymotrypsin. By contrast, the dense matted deposits formed from FBG in the presence of ferric ions are remarkably resistant to proteolytic and chemical degradations due to the presence of inter-molecular hydrophobic bonds. Thus, we postulate that this iron-catalyzed reaction represents a novel blood coagulation pathway operating in degenerative diseases. By means of SEM, we showed the presence of dense fibrin-like deposits in the blood of diabetic patients. Therefore, the prothrombotic state and cardiovascular complications observed in diabetes can be explained in terms of the persistent in vivo action of free iron. This phenomenon may explain hemorheologic disturbances in patients with metabolic syndrome and other diseases caused by iron overload. Of note, HRs can be effectively scavenged by phenolic substances; therefore, certain natural polyphenolic substances, which also scavenge HRs, may be considered to have a potential antidiabetic effect. Moreover, natural or synthetic iron-binding substances may also be considered as a new class of antidiabetic drugs. C1 [Lipinski, Boguslaw] Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02215 USA. [Pretorius, Etheresia] Univ Pretoria, Fac Hlth Sci, Dept Physiol, Arcadia, South Africa. RP Lipinski, B (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, 1 Joslin Pl, Boston, MA 02215 USA. EM b.lipinski2006@rcn.com NR 69 TC 40 Z9 41 U1 0 U2 10 PU MEDYCYNA PRAKTYCZNA PI KRAKOW PA UL KRAKOWSKA 41, KRAKOW, 31-066, POLAND SN 0032-3772 J9 POL ARCH MED WEWN JI Pol. Arch. Med. Wewn. PY 2012 VL 122 IS 3 BP 115 EP 122 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 922HG UT WOS:000302537400006 PM 22460041 ER PT J AU Coviello, DM Cornish, JW Lynch, KG Boney, TY Clark, CA Lee, JD Friedmann, PD Nunes, EV Kinlock, TW Gordon, MS Schwartz, RP Nuwayser, ES O'Brien, CP AF Coviello, Donna M. Cornish, James W. Lynch, Kevin G. Boney, Tamara Y. Clark, Cynthia A. Lee, Joshua D. Friedmann, Peter D. Nunes, Edward V. Kinlock, Timothy W. Gordon, Michael S. Schwartz, Robert P. Nuwayser, Elie S. O'Brien, Charles P. TI A Multisite Pilot Study of Extended-Release Injectable Naltrexone Treatment for Previously Opioid-Dependent Parolees and Probationers SO SUBSTANCE ABUSE LA English DT Article DE Extended-release naltrexone; opioid dependence; Depotrex; addiction pharmacotherapy; offenders; heroin ID ADDICTION SEVERITY INDEX; METHADONE-MAINTENANCE; RANDOMIZED-TRIAL; COCAINE USE; FOLLOW-UP; BUPRENORPHINE; PLACEBO; INDIVIDUALS; RELIABILITY; PREDICTORS AB A feasibility study was conducted to pilot test the ability of 5 sites to recruit, treat, and retain opioid-dependent offenders in a trial of extended-release injectable naltrexone (XR-NTX). The participants, 61 previously opioid-dependent individuals under legal supervision in the community, received up to 6 monthly injections of Depotrex brand naltrexone and completed a 6-month follow-up interview. Six-month outcomes showed that those who completed treatment had significantly fewer opioid-positive urines and were less likely to have been incarcerated than those who had not completed treatment. The findings indicate that XR-NTX holds promise as a feasible, effective treatment option for opioid-dependent offenders. C1 [Coviello, Donna M.; Cornish, James W.; Lynch, Kevin G.; Boney, Tamara Y.; Clark, Cynthia A.; O'Brien, Charles P.] Univ Penn, Philadelphia, PA 19104 USA. [Cornish, James W.; O'Brien, Charles P.] Vet Affairs Med Ctr, Philadelphia, PA USA. [Lee, Joshua D.] NYU, Bellevue Hosp, New York, NY USA. [Friedmann, Peter D.] Rhode Isl Hosp, Vet Affairs Med Ctr, Providence, RI USA. [Friedmann, Peter D.] Brown Univ, Providence, RI 02912 USA. [Nunes, Edward V.] Columbia Univ, New York, NY USA. [Kinlock, Timothy W.; Gordon, Michael S.; Schwartz, Robert P.] Friends Res Inst, Baltimore, MD USA. [Kinlock, Timothy W.] Univ Baltimore, Baltimore, MD 21201 USA. [Nuwayser, Elie S.] Biotek Inc, Woburn, MA USA. RP Coviello, DM (reprint author), Treatment Res Ctr, 3440 Market St,Suite 370, Philadelphia, PA 19104 USA. EM coviello_d@mail.trc.upenn.edu FU National Institute on Drug Abuse [R01-DA-012268-05]; Dana foundation FX The study was supported by grants from the National Institute on Drug Abuse (R01-DA-012268-05) and the Dana foundation. NR 42 TC 24 Z9 24 U1 3 U2 6 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 0889-7077 J9 SUBST ABUS JI Subst. Abus. PY 2012 VL 33 IS 1 SI SI BP 48 EP 59 DI 10.1080/08897077.2011.609438 PG 12 WC Substance Abuse SC Substance Abuse GA 923HE UT WOS:000302609500007 PM 22263713 ER PT J AU Huddle, TS AF Huddle, Thomas S. TI Honesty Is an Internal Norm of Medical Practice and the Best Policy SO AMERICAN JOURNAL OF BIOETHICS LA English DT Editorial Material C1 [Huddle, Thomas S.] Univ Alabama, Sch Med, Birmingham, AL 35294 USA. [Huddle, Thomas S.] Birmingham VA Med Ctr, Birmingham, AL USA. RP Huddle, TS (reprint author), Univ Alabama, Sch Med, 1530 3rd Ave S, Birmingham, AL 35294 USA. EM thuddle@uab.edu NR 9 TC 1 Z9 1 U1 0 U2 2 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 1526-5161 J9 AM J BIOETHICS JI Am. J. Bioeth. PY 2012 VL 12 IS 3 BP 15 EP 17 DI 10.1080/15265161.2012.656812 PG 3 WC Ethics; Medical Ethics; Social Issues; Social Sciences, Biomedical SC Social Sciences - Other Topics; Medical Ethics; Social Issues; Biomedical Social Sciences GA 919BW UT WOS:000302296600004 PM 22416742 ER PT J AU Roosli, C Linthicum, FH Cureoglu, S Merchant, SN AF Roosli, Christof Linthicum, Fred H., Jr. Cureoglu, Sebahattin Merchant, Saumil N. TI What Is the Site of Origin of Cochleovestibular Schwannomas? SO AUDIOLOGY AND NEURO-OTOLOGY LA English DT Article DE Vestibular schwannoma; Histopathology, temporal bone; Origin; Obersteiner-Redlich zone; Glial-Schwann cell transition zone ID ACOUSTIC NEUROMA; NERVE ORIGIN; BRAIN TUMORS; EAR AB The belief that cochleovestibular schwannomas arise from the glial-Schwann cell junction has repeatedly been quoted in the literature, although there is no published evidence that supports this statement. A systematic evaluation of the nerve of origin and the precise location of cochleovestibular schwannomas using our respective archival temporal bone collections was conducted. Forty tumors were within the internal auditory canal (IAC), while 10 were intralabyrinthine neoplasms. Of the 40 IAC schwannomas, 4 arose from the cochlear nerve, and 36 from the vestibular nerve. Twenty-one tumors clearly arose lateral to the glial-Schwann cell junction, while 16 tumors filled at least two thirds of the IAC, with the epicenter of the neoplasm located in the mid part or the lateral part of the IAC. Only 3 schwannomas were located in the medial one third of the IAC in the area of the glial-Schwann cell junction. We concluded that cochleovestibular schwannomas may arise anywhere along the course of the axons of the eighth cranial nerve from the glial-Schwann sheath junction up until their terminations within the auditory and vestibular end organs. Copyright (C) 2011 S. Karger AG, Basel C1 [Roosli, Christof; Merchant, Saumil N.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA 02114 USA. [Linthicum, Fred H., Jr.] House Ear Res Inst, Los Angeles, CA USA. [Cureoglu, Sebahattin] Univ Minnesota, Dept Otolaryngol, Minneapolis, MN USA. [Roosli, Christof] Univ Zurich Hosp, Clin Otorhinolaryngol Head & Neck Surg, CH-8091 Zurich, Switzerland. RP Roosli, C (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, 243 Charles St, Boston, MA 02114 USA. EM christof_roosli@meei.harvard.edu FU NIH (National Institute on Deafness and Other Communication Disorders) [U24DC011943] FX The authors wish to thank Jon Pack for the photomicrographs. This study was supported by funding from NIH (National Institute on Deafness and Other Communication Disorders) grant No. U24DC011943. NR 28 TC 11 Z9 12 U1 1 U2 4 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1420-3030 J9 AUDIOL NEURO-OTOL JI Audiol. Neuro-Otol. PY 2012 VL 17 IS 2 BP 121 EP 125 DI 10.1159/000331394 PG 5 WC Audiology & Speech-Language Pathology; Neurosciences; Otorhinolaryngology SC Audiology & Speech-Language Pathology; Neurosciences & Neurology; Otorhinolaryngology GA 916XN UT WOS:000302136600006 PM 21968195 ER PT J AU Badesch, DB Feldman, J Keogh, A Mathier, MA Oudiz, RJ Shapiro, S Farber, HW McGoon, M Frost, A Allard, M Despain, D Dufton, C Rubin, LJ AF Badesch, David B. Feldman, Jeremy Keogh, Anne Mathier, Michael A. Oudiz, Ronald J. Shapiro, Shelley Farber, Harrison W. McGoon, Michael Frost, Adaani Allard, Martine Despain, Darrin Dufton, Christopher Rubin, Lewis J. CA ARIES 3 Study Grp TI ARIES-3: Ambrisentan Therapy in a Diverse Population of Patients with Pulmonary Hypertension SO CARDIOVASCULAR THERAPEUTICS LA English DT Article DE Ambrisentan; Non-Group 1 patient population; Prostacyclin analog therapy; Pulmonary hypertension; Sildenafil therapy ID CLINICAL-PRACTICE GUIDELINES; ARTERIAL-HYPERTENSION; DOUBLE-BLIND; FIBROSIS AB Introduction: Ambrisentan is an oral, once daily, endothelin receptor antagonist approved for treatment of pulmonary arterial hypertension (PAH). Previous studies of ambrisentan were limited to patients with Group 1 PAH and often excluded patients receiving other pulmonary hypertension (PH) therapies. Aims: ARIES-3 was an open-label study evaluating efficacy and safety of ambrisentan in patients with various PH etiologies and background PH medications. Patients received 5 mg ambrisentan once daily for 24 weeks. The primary endpoint was change from baseline in 6-minute walk distance (6MWD) at week 24. Results: A total of 224 patients with PH due to idiopathic and familial PAH (31%), connective tissue disease (18%), chronic hypoxemia (22%), chronic thromboembolic disease (13%), or other etiologies (16%) were enrolled and 53% of patients received stable background PAH therapies. After 24 weeks of therapy, an increase in 6MWD (+21 m; 95% CI: 1229) and a decrease in B-type natriuretic peptide (26%; 95% CI: 34 to 16%) was observed in the overall population compared to baseline; however, increases in 6MWD were not observed in several non-Group 1 PH subpopulations. Peripheral edema, headache, and dyspnea were the most common adverse events. Conclusion: This study reconfirms the results of previous placebo-controlled studies, which demonstrate that ambrisentan is well tolerated and provides benefit in patients with PAH. Definitive conclusions regarding the safety and efficacy of ambrisentan in specific non-Group 1 PH etiologies cannot be determined and larger, controlled studies will be necessary to determine the efficacy and safety of ambrisentan in these populations. C1 [Badesch, David B.] Univ Colorado, Clin Res Ctr, Aurora, CO 80045 USA. [Feldman, Jeremy] Arizona Pulm Specialists Ltd, Phoenix, AZ USA. [Keogh, Anne] St Vincents Hosp, Sydney, NSW 2010, Australia. [Mathier, Michael A.] Univ Pittsburgh, Pittsburgh, PA USA. [Oudiz, Ronald J.] Harbor UCLA Med Ctr, LA Biomed Res Inst, Torrance, CA 90509 USA. [Shapiro, Shelley] VA Greater Angeles VA Healthcare Syst, Los Angeles, CA USA. [Shapiro, Shelley] David Geffen UCLA Sch Med, Los Angeles, CA USA. [Farber, Harrison W.] Boston Univ, Sch Med, Boston, MA 02118 USA. [McGoon, Michael] Mayo Clin, Rochester, MN USA. [Frost, Adaani] Baylor Coll Med, Houston, TX 77030 USA. [Allard, Martine; Despain, Darrin; Dufton, Christopher] Gilead Sci Inc, Foster City, CA 94404 USA. [Rubin, Lewis J.] UCSD, La Jolla, CA USA. RP Badesch, DB (reprint author), Univ Colorado, Clin Res Ctr, Leprino Bldg,Rm 536,12401 E 17th Ave, Aurora, CO 80045 USA. EM David.Badesch@ucdenver.edu OI Farber, Harrison/0000-0002-0297-7902 FU Gilead Sciences Inc., Foster City, California, USA FX This study was sponsored by Gilead Sciences Inc., Foster City, California, USA. NR 21 TC 34 Z9 39 U1 0 U2 7 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1755-5914 J9 CARDIOVASC THER JI Cardiovasc. Ther. PY 2012 VL 30 IS 2 BP 93 EP 99 DI 10.1111/j.1755-5922.2011.00279.x PG 7 WC Cardiac & Cardiovascular Systems; Pharmacology & Pharmacy SC Cardiovascular System & Cardiology; Pharmacology & Pharmacy GA 907UE UT WOS:000301443500010 PM 21884013 ER PT J AU Souza, LCS Payabvash, S Wang, YF Kamalian, S Schaefer, P Gonzalez, RG Furie, KL Lev, MH AF Souza, Leticia C. S. Payabvash, Seyedmehdi Wang, Yifei Kamalian, Shervin Schaefer, Pamela Gonzalez, R. Gilberto Furie, Karen L. Lev, Michael H. TI Admission CT Perfusion Is an Independent Predictor of Hemorrhagic Transformation in Acute Stroke with Similar Accuracy to DWI SO CEREBROVASCULAR DISEASES LA English DT Article DE Stroke; Hemorrhagic transformation; CT scan; Perfusion ID ACUTE ISCHEMIC-STROKE; TISSUE-PLASMINOGEN ACTIVATOR; BRAIN-BARRIER PERMEABILITY; COOPERATIVE ACUTE STROKE; THROMBOLYTIC THERAPY; INFARCT; VOLUME; ECASS; RISK; SIZE AB Background: The utility of admission CT perfusion (CTP) to that of diffusion-weighted imaging (DWI) as a predictor of hemorrhagic transformation (HT) in acute stroke was compared. Methods: We analyzed the admission CTP and DWI scans of 96 consecutive stroke patients. HT was present in 22 patients (23%). Infarct core was manually segmented on the admission DWI. We determined the: (1) hypoperfused tissue volume in the ischemic hemisphere using a range of thresholds applied to multiple different CTP parameter maps, and (2) mean relative CTP (rCTP) voxel values within both the DWI-segmented lesions and the thresholded CTP parameter maps. Receiver operating characteristic area under curve (AUC) analysis and multivariate regression were used to evaluate the test characteristics of each set of volumes and mean rCTP parameter values as predictors of HT. Results: The hypoperfused tissue volumes with either relative cerebral blood flow (rCBF) <0.48 (AUC = 0.73), or relative mean transit time (rMTT) >1.3 (AUC = 0.70), had similar accuracy to the DWI-segmented core volume (AUC = 0.68, p = 0.2 and p = 0.1, respectively) as predictors of HT. The mean rMTT voxel values within the rMTT >1.3 segmented lesion (AUC = 0.71) had similar accuracy to the mean rMTT voxel values ( AUC = 0.65, p = 0.24) and mean rCBF voxel values (AUC = 0.64, p = 0.22) within the DWI-segmented lesion. The only independent predictors of HT were: (1) mean rMTT with rMTT >1.3, and (2) mechanical thrombectomy. Conclusion: Admission CTP-based hypoperfused tissue volumes and thresholded mean voxel values are markers of HT in acute stroke, with similar accuracy to DWI. This could be of value when MRI cannot be obtained. Copyright (c) 2011 S. Karger AG, Basel C1 [Souza, Leticia C. S.; Payabvash, Seyedmehdi; Kamalian, Shervin; Schaefer, Pamela; Gonzalez, R. Gilberto; Lev, Michael H.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Furie, Karen L.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. [Wang, Yifei] Univ Western Ontario, Schulich Sch Med & Dent, London, ON, Canada. RP Lev, MH (reprint author), Massachusetts Gen Hosp, Dept Radiol, GRB285,POB 9657, Boston, MA 02114 USA. EM mlev@partners.org RI Kamalian, Shervin/D-7667-2013 OI Kamalian, Shervin/0000-0001-8962-4773 FU Translational Research in Acute Stroke (SPOTRIAS) Network; National Institute of Health (NIH) [P50 NS051343]; Massachusetts General Hospital Clinical Research Center [1 UL1 RR025758-01]; Harvard Clinical and Translational Science Center, from the National Center for Research Resources; Agency for Healthcare Research and Quality AHRQ [R01 HS11392] FX This work was supported by the Specialized Programs of Translational Research in Acute Stroke (SPOTRIAS) Network grant funded by the National Institute of Health (NIH; P50 NS051343), the Agency for Healthcare Research and Quality grant AHRQ R01 HS11392, and the Massachusetts General Hospital Clinical Research Center (No. 1 UL1 RR025758-01) Harvard Clinical and Translational Science Center, from the National Center for Research Resources. NR 20 TC 14 Z9 18 U1 0 U2 2 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1015-9770 J9 CEREBROVASC DIS JI Cerebrovasc. Dis. PY 2012 VL 33 IS 1 BP 8 EP 15 DI 10.1159/000331914 PG 8 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 916XG UT WOS:000302135900003 PM 22143195 ER PT J AU Bowden, CL Perlis, RH Thase, ME Ketter, TA Ostacher, MM Calabrese, JR Reilly-Harrington, NA Gonzalez, JM Singh, V Nierenberg, AA Sachs, GS AF Bowden, C. L. Perlis, R. H. Thase, M. E. Ketter, T. A. Ostacher, M. M. Calabrese, J. R. Reilly-Harrington, N. A. Gonzalez, J. M. Singh, V. Nierenberg, A. A. Sachs, G. S. TI Aims and Results of the NIMH Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD) SO CNS NEUROSCIENCE & THERAPEUTICS LA English DT Review DE Neuropsychopharmacology; Mood Disorders; Bipolar; Treatment ID RANDOMIZED EFFECTIVENESS TRIAL; QUALITY-OF-LIFE; DEPRESSIVE EPISODES; COLLABORATIVE CARE; ANTIDEPRESSANT USE; MANIC SYMPTOMS; PARTICIPANTS; COMORBIDITY; RECURRENCE; RECOVERY AB The Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD) was funded as part of a National Institute of Mental Health initiative to develop effectiveness information about treatments, illness course, and assessment strategies for severe mental disorders. STEP-BD studies were planned to be generalizable both to the research knowledge base for bipolar disorder and to clinical care of bipolar patients. Several novel methodologies were developed to aid in illness characterization, and were combined with existing scales on function, quality of life, illness burden, adherence, adverse effects, and temperament to yield a comprehensive data set. The methods integrated naturalistic treatment and randomized clinical trials, which a portion of STEP-BD participants participated. All investigators and other researchers in this multisite program were trained in a collaborative care model with the objective of retaining a high percentage of enrollees for several years. Articles from STEP-BD have yielded evidence on risk factors impacting outcomes, suicidality, functional status, recovery, relapse, and caretaker burden. The findings from these studies brought into question the widely practiced use of antidepressants in bipolar depression as well as substantiated the poorly responsive course of bipolar depression despite use of combination strategies. In particular, large studies on the characteristics and course of bipolar depression (the more pervasive pole of the illness), and the outcomes of treatments concluded that adjunctive psychosocial treatments but not adjunctive antidepressants yielded outcomes superior to those achieved with mood stabilizers alone. The majority of patients with bipolar depression concurrently had clinically significant manic symptoms. Anxiety, smoking, and early age of bipolar onset were each associated with increased illness burden. STEP-BD has established procedures that are relevant to future collaborative research programs aimed at the systematic study of the complex, intrinsically important elements of bipolar disorders. C1 [Bowden, C. L.; Gonzalez, J. M.; Singh, V.] Univ Texas Hlth Sci Ctr San Antonio, Dept Psychiat, San Antonio, TX 78229 USA. [Perlis, R. H.; Reilly-Harrington, N. A.; Nierenberg, A. A.; Sachs, G. S.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat,Partners Bipolar Treatment Ctr, Boston, MA USA. [Thase, M. E.] Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA. [Ketter, T. A.; Ostacher, M. M.] Stanford Univ, Dept Psychiat & Behav Sci, Sch Med, Stanford, CA 94305 USA. [Calabrese, J. R.] Case Western Reserve Univ, Sch Med, Dept Psychiat, Cleveland, OH USA. RP Bowden, CL (reprint author), 7703 Floyd Curl Dr,MC 7734, San Antonio, TX 78229 USA. EM bowdenc@uthscsa.edu OI Ostacher, Michael/0000-0003-0353-7535 FU NIMH [N01MH80001] FX Supported by NIMH Contract N01MH80001, 1998-2005, GS Sachs, P. I. Massachusetts General Hospital, Boston. Additional detail on STEP-BD can be located at http://www.nimh.nih.gov/health/trials/practical/step-bd/questions-and-an swers-for-the-systematic-treatment-enhancement-program-for-bipolar-disor der-step-bd-study- background.shtml. NR 43 TC 19 Z9 19 U1 1 U2 15 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1755-5930 EI 1755-5949 J9 CNS NEUROSCI THER JI CNS Neurosci. Ther. PY 2012 VL 18 IS 3 BP 243 EP 249 DI 10.1111/j.1755-5949.2011.00257.x PG 7 WC Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA 906KK UT WOS:000301343800010 PM 22070541 ER PT J AU Zeidan, MA Lebron-Milad, K Thompson-Hollands, J Im, JJY Dougherty, DD Holt, DJ Orr, SP Milad, MR AF Zeidan, Mohamed A. Lebron-Milad, Kelimer Thompson-Hollands, Johanna Im, Jamie J. Y. Dougherty, Darin D. Holt, Daphne J. Orr, Scott P. Milad, Mohammed R. TI Test-Retest Reliability during Fear Acquisition and Fear Extinction in Humans SO CNS NEUROSCIENCE & THERAPEUTICS LA English DT Article DE Anxiety disorders; Fear conditioning; Fear extinction; Test-retest ID POSTTRAUMATIC-STRESS-DISORDER; VENTROMEDIAL PREFRONTAL CORTEX; MEMORY; INHIBITION; ACTIVATION; MECHANISMS; AMYGDALA; THERAPY; CONTEXT; PTSD AB Aims: Classical fear conditioning and extinction has been used to understand the neurobiology of fear learning and its inhibition. The recall of an extinction memory involves the ventromedial prefrontal cortex and the amygdala, and patients with posttraumatic stress disorder (PTSD) have been shown to exhibit deficits in this process. Furthermore, extinction forms the basis of exposure therapies commonly used to treat PTSD patients. It is possible that effective pharmacological and/or psychological treatment regimens could influence the activity of these regions, and thereby increase the ability to retain an extinction memory. However, to test this, a fear conditioning and extinction paradigm must demonstrate within-subject reproducibility over time. We, therefore, sought to test the within-subject reliability of a previously used 2-day, classical fear conditioning and extinction paradigm. Methods: Eighteen healthy participants participated in a 2-day paradigm on three occasions, each separated by at least 12 weeks. Conditioning and extinction took place on Day 1, and extinction recall and fear renewal were evaluated on Day 2 on each of the three occasions. The conditioned stimulus was a visual cue and the unconditioned stimulus was a mild electric shock to the fingers. Skin conductance was recorded throughout the experiment to measure conditioned responses. Results: We found that conditioning and extinction recall were not significantly different across time and were correlated within subjects. Conclusion: These data illustrate the reliability of this paradigm and its potential usefulness in evaluating the influence of a given treatment on the fear extinction network in longitudinal within-subject designs. C1 [Milad, Mohammed R.] Harvard Univ, Sch Med, Dept Psychiat, Charlestown, MA 02129 USA. [Zeidan, Mohamed A.; Lebron-Milad, Kelimer; Thompson-Hollands, Johanna; Im, Jamie J. Y.; Dougherty, Darin D.; Holt, Daphne J.; Orr, Scott P.; Milad, Mohammed R.] Massachusetts Gen Hosp, Dept Psychiat, Charlestown, MA 02129 USA. [Orr, Scott P.] Dept Vet Affairs Med Ctr, Res Serv, Manchester, NH USA. RP Milad, MR (reprint author), Harvard Univ, Sch Med, Dept Psychiat, 149 13th St,CNY 2614, Charlestown, MA 02129 USA. EM milad@nmr.mgh.harvard.edu FU National Institute of Mental Health [R01MH081975-01A1]; Wyeth; Jazz Pharmaceuticals; Bristol Myers Squibb; Brand Ideas; Reed Elsevier; Medtronic; Cyberonics; Eli Lilly; McNeil; Northstar; Microtranspondor; [MH086400] FX This work was supported by a grant from the National Institute of Mental Health (R01MH081975-01A1) to M.R.M. The project described was also supported by Grant MH086400 to M.RM. and D.D.D. 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.; Darin D. Dougherty, MD has received honoraria, consultation fees, and/or royalties from Wyeth, Jazz Pharmaceuticals, Bristol Myers Squibb, Brand Ideas, and Reed Elsevier. He has also participated in research funded by Medtronic, Cyberonics, Eli Lilly, McNeil, and Northstar. Mohammed R. Milad, PhD received consultation fees from Microtranspondor. The remaining authors have no financial disclosures to report. NR 21 TC 9 Z9 9 U1 3 U2 10 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1755-5930 J9 CNS NEUROSCI THER JI CNS Neurosci. Ther. PY 2012 VL 18 IS 4 BP 313 EP 317 DI 10.1111/j.1755-5949.2011.00238.x PG 5 WC Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA 919UM UT WOS:000302355000006 PM 21592319 ER PT S AU Yardley, H Perlovsky, L Bar, M AF Yardley, Helena Perlovsky, Leonid Bar, Moshe BE Weinshall, D Anemuller, J VanGool, L TI Predictions and Incongruency in Object Recognition: A Cognitive Neuroscience Perspective SO DETECTION AND IDENTIFICATION OF RARE AUDIOVISUAL CUES SE Studies in Computational Intelligence LA English DT Proceedings Paper CT DIRAC Workshop on Detection and Identification of Rare Audiovisual Cues CY SEP 24, 2010 CL Barcelona, SPAIN ID TOP-DOWN FACILITATION; MEDIAL PREFRONTAL CORTEX; CORTICAL ACTIVITY; RHESUS-MONKEY; VISUAL-CORTEX; TEMPORAL CORTEX; NEURAL ACTIVITY; AFFERENT INPUT; FRONTAL-LOBE; ORGANIZATION AB The view presented here is that visual object recognition is the product of interaction between perception and cognition, a process budding from memories of past events. Our brain is proactive, in that it is continuously aiming to predict how the future will unfold, and this inherent ability allows us to function optimally in our environment. Our memory serves as a database from which we can form analogies from our past experiences, and apply them to the current moment. We arc able to recognize an object through top-down and bottom-up processing pathways, which integrate to facilitate successful and timely object recognition. Specifically, it is argued that when we encounter an object our brain asks "what is this like" and therefore draws on years of experience, stored in memory, to generate predictions that directly facilitate perception. These feed-forward and feedback systems time our perceptive and cognitive faculties based on a number of factors: predictive astuteness, context, personal relevance of the given event, and the degree to which its potential rarity differs from our original expectations. We discuss both computational and theoretical models of object recognition, and review evidence to support the theory that we do not merely process incoming information serially, and that during our attempts to interpret the world around us, perception relies on existing knowledge as much as it does on incoming information. C1 [Yardley, Helena] Massachusetts Gen Hosp, Madinos Ctr Biomed Imaging, Boston, MA 02114 USA. RP Yardley, H (reprint author), Massachusetts Gen Hosp, Madinos Ctr Biomed Imaging, Boston, MA 02114 USA. EM helena.yardley@gmail.com; leonid@seas.harvard.edu; bar@mmr.mgh.harvard.edu NR 91 TC 2 Z9 2 U1 0 U2 3 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 1860-949X BN 978-3-642-24033-1 J9 STUD COMPUT INTELL PY 2012 VL 384 BP 139 EP 153 PG 15 WC Computer Science, Artificial Intelligence; Computer Science, Information Systems; Engineering, Electrical & Electronic SC Computer Science; Engineering GA BZM19 UT WOS:000302002500013 ER PT J AU Cevasco, M Haime, M AF Cevasco, Marisa Haime, Miguel TI Response to Letter to the Editor: Aortic Valve Endocarditis SO JOURNAL OF CARDIAC SURGERY LA English DT Letter C1 [Cevasco, Marisa] Brigham & Womens Hosp, Dept Surg, Boston, MA 02115 USA. [Haime, Miguel] Boston Healthcare Syst, Vet Affairs, Boston, MA USA. [Haime, Miguel] Harvard Univ, Sch Med, Boston, MA USA. RP Cevasco, M (reprint author), Brigham & Womens Hosp, Dept Surg, 75 Francis St, Boston, MA 02115 USA. EM mcevasco@partners.org NR 1 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0886-0440 J9 J CARDIAC SURG JI J. Card. Surg. PD JAN PY 2012 VL 27 IS 1 BP 64 EP 64 DI 10.1111/j.1540-8191.2011.01371.x PG 1 WC Cardiac & Cardiovascular Systems; Surgery SC Cardiovascular System & Cardiology; Surgery GA 917JX UT WOS:000302172000015 ER PT J AU Theruvath, TP Jones, JA Ikonomidis, JS AF Theruvath, Tom P. Jones, Jeffrey A. Ikonomidis, John S. TI Matrix Metalloproteinases and Descending Aortic Aneurysms: Parity, Disparity, and Switch SO JOURNAL OF CARDIAC SURGERY LA English DT Review ID SMOOTH-MUSCLE-CELLS; GROWTH-FACTOR-BETA; ASCENDING THORACIC AORTA; INCREASED PLASMA-LEVELS; IN-SITU LOCALIZATION; TISSUE INHIBITORS; ABDOMINAL-AORTA; MURINE MODEL; INTERSTITIAL COLLAGENASE; DILATATIVE PATHOLOGY AB Central to the pathologic changes in developing aortic aneurysms are alterations in the abundance and activity of proteases, of which the most important for aneurysm production comprise the matrix metalloproteinase (MMP) family. In this review, literature demonstrating the role of MMPs in the development of aortic aneurysms is presented, with emphasis on the parity and disparity between the thoracic and abdominal aorta. Furthermore, the role of embryologic cellular origins and evidence of phenotypic switch will be addressed in terms of how this process alters MMP production during aneurysm development. doi: 10.1111/j.1540-8191.2011.01315.x (J Card Surg 2012;27:81-90) C1 [Ikonomidis, John S.] Med Univ S Carolina, Dept Surg, Div Cardiothorac Surg, Charleston, SC 29425 USA. Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC USA. RP Ikonomidis, JS (reprint author), Med Univ S Carolina, Dept Surg, Div Cardiothorac Surg, 25 Courtenay Dr, Charleston, SC 29425 USA. EM ikonomij@musc.edu FU NIH/NHLBI [R21 HL089170, R01 HL102121] FX This manuscript was supported by NIH/NHLBI grants R21 HL089170 and R01 HL102121. NR 100 TC 12 Z9 14 U1 0 U2 3 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0886-0440 J9 J CARDIAC SURG JI J. Card. Surg. PD JAN PY 2012 VL 27 IS 1 BP 81 EP 90 DI 10.1111/j.1540-8191.2011.01315.x PG 10 WC Cardiac & Cardiovascular Systems; Surgery SC Cardiovascular System & Cardiology; Surgery GA 917JX UT WOS:000302172000020 PM 21958052 ER PT J AU Blum, K Werner, T Carnes, S Carnes, P Bowirrat, A Giordano, J Marlene-Oscar-Berman Gold, M AF Blum, Kenneth Werner, Tonia Carnes, Stefanie Carnes, Patrick Bowirrat, Abdalla Giordano, John Marlene-Oscar-Berman Gold, Mark TI Sex, Drugs, and Rock 'N' Roll: Hypothesizing Common Mesolimbic Activation as a Function of Reward Gene Polymorphisms SO JOURNAL OF PSYCHOACTIVE DRUGS LA English DT Article DE dopamine; mesolimbic systems; neurogenetics; reward deficiency syndrome (RDS); sexual addiction ID DOPAMINE-D4 RECEPTOR GENE; NUCLEUS-ACCUMBENS; ROMANTIC LOVE; ALLELIC ASSOCIATION; DEFICIENCY SYNDROME; PENILE ERECTION; VIDEO GAME; MEN; STIMULATION; BEHAVIOR AB The nucleus accumbens, a site within the ventral striatum, plays a prominent role in mediating the reinforcing effects of drugs of abuse, food, sex, and other addictions. Indeed, it is generally believed that this structure mandates motivated behaviors such as eating, drinking, and sexual activity, which are elicited by natural rewards and other strong incentive stimuli. This article focuses on sex addiction, but we hypothesize that there is a common underlying mechanism of action for the powerful effects that all addictions have on human motivation. That is, biological drives may have common molecular genetic antecedents, which if impaired, lead to aberrant behaviors. Based on abundant scientific support, we further hypothesize that dopaminergic genes, and possibly other candidate neurotransmitter-related gene polymorphisms, affect both hedonic and anhedonic behavioral outcomes. Genotyping studies already have linked gene polymorphic associations with alcohol and drug addictions and obesity, and we anticipate that future genotyping studies of sex addicts will provide evidence for polymorphic associations with specific clustering of sexual typologies based on clinical instrument assessments. We recommend that scientists and clinicians embark on research coupling the use of neuroimaging tools with dopaminergic agonistic agents to target specific gene polymorphisms systematically for normalizing hyper- or hypo-sexual behaviors. C1 [Blum, Kenneth; Gold, Mark] Univ Florida, Dept Psychiat, Coll Med, Gainesville, FL 32610 USA. [Blum, Kenneth; Gold, Mark] McKnight Brain Inst, Gainesville, FL USA. [Blum, Kenneth; Giordano, John] G&G Holist Addict Treatment Ctr, Dept Holist Med, N Miami Beach, FL USA. [Werner, Tonia] Univ Florida, Dept Psychiat, Forens Inst, Gainesville, FL 32610 USA. [Carnes, Stefanie; Carnes, Patrick] Pine Grove Behav Ctr, Gentle Path Program, Hattiesburg, MS USA. [Bowirrat, Abdalla] Nazareth Hosp, EMMS Nazareth, IL-16100 Nazareth, Israel. [Marlene-Oscar-Berman] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. [Marlene-Oscar-Berman] Boston Univ, Sch Med, Dept Anat & Neurobiol, Boston, MA 02118 USA. [Marlene-Oscar-Berman] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02118 USA. [Marlene-Oscar-Berman] Boston VA Healthcare Syst, Boston, MA USA. RP Blum, K (reprint author), Univ Florida, Dept Psychiat, Coll Med, Box 100256, Gainesville, FL 32610 USA. EM drd2gene@aol.com FU NIAAA NIH HHS [K05 AA000219, R01-AA07112, R01 AA007112] NR 122 TC 14 Z9 14 U1 12 U2 38 PU HAIGHT-ASHBURY PUBL PI SAN FRANCISCO PA 409 CLAYTON ST, SAN FRANCISCO, CA 94117 USA SN 0279-1072 J9 J PSYCHOACTIVE DRUGS JI J. Psychoact. Drugs PD JAN-MAR PY 2012 VL 44 IS 1 BP 38 EP 55 DI 10.1080/02791072.2012.662112 PG 18 WC Psychology, Clinical; Substance Abuse SC Psychology; Substance Abuse GA 917VR UT WOS:000302207200005 PM 22641964 ER PT J AU Lally, RM Underhill, ML AF Lally, Robin M. Underhill, Meghan L. TI Transition to Breast Cancer Survivorship: A Longitudinal Qualitative Follow-Up Study of Two-Year Survivors SO JOURNAL OF PSYCHOSOCIAL ONCOLOGY LA English DT Article DE breast cancer; survivorship; adjustment; longitudinal; qualitative ID LONG-TERM SURVIVORS; PSYCHOLOGICAL ADJUSTMENT; OF-LIFE; COPING STRATEGIES; EMOTIONAL DISTRESS; 1ST YEAR; WOMEN; DIAGNOSIS; PREVALENCE; DEPRESSION AB This article reports on a qualitative, longitudinal follow-up of a cohort of breast cancer survivors through which their pretreatment psychological adjustment thought processes and behaviors were compared with those 2 years following diagnosis. Analysis revealed five interrelated themes reflecting changing thought processes and behaviors over time. Quantitative measures of psychological adjustment at 2 years were consistent with the qualitative findings in some respects; however, the concepts measured by these tools were inconsistent with themes identified through qualitative analysis. Findings support a need to study ways to assess women's psychosocial needs and intervene to support adjustment among 2-year breast cancer survivors. C1 [Lally, Robin M.] SUNY Buffalo, Sch Nursing, Buffalo, NY 14214 USA. [Lally, Robin M.] Roswell Pk Canc Inst, Buffalo, NY 14263 USA. [Underhill, Meghan L.] Univ Massachusetts, Boston, MA 02125 USA. [Underhill, Meghan L.] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Lally, RM (reprint author), SUNY Buffalo, Sch Nursing, 3435 Main St,304D Wende Hall, Buffalo, NY 14214 USA. EM rmlally@buffalo.edu OI Underhill, Meghan/0000-0002-1433-5915 NR 62 TC 3 Z9 3 U1 0 U2 7 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 0734-7332 J9 J PSYCHOSOC ONCOL JI J. Psychosoc. Oncol. PY 2012 VL 30 IS 1 BP 97 EP 127 DI 10.1080/07347332.2011.633983 PG 31 WC Psychology, Social SC Psychology GA 918AU UT WOS:000302222000006 PM 22269078 ER PT J AU Maserejian, NN Shifren, J Parish, SJ Segraves, RT Huang, LY Rosen, RC AF Maserejian, Nancy N. Shifren, Jan Parish, Sharon J. Segraves, R. Taylor Huang, Liyuan Rosen, Raymond C. TI Sexual Arousal and Lubrication Problems in Women With Clinically Diagnosed Hypoactive Sexual Desire Disorder: Preliminary Findings from the Hypoactive Sexual Desire Disorder Registry for Women SO JOURNAL OF SEX & MARITAL THERAPY LA English DT Article ID FUNCTION INDEX FSFI; POPULATION-BASED SAMPLE; MENOPAUSAL STATUS; DYSFUNCTION; VALIDATION; DISTRESS; PREVALENCE; INSTRUMENT; TRANSITION; HEALTH AB Sexual desire and arousal difficulties are often correlated in women. However, no studies have examined characteristics of women with clinically diagnosed hypoactive sexual desire disorder (HSDD) that increase the likelihood of co-occurring arousal difficulties. The authors examined combined HSDD and arousal/lubrication problems using baseline cross-sectional data from the HSDD Registry for Women. Their analyses were restricted to women who could be classified with certainty as having arousal or lubrication difficulties by the Female Sexual Function Index (requiring sexually activity in the past 4 weeks). Results showed that among 426 premenopausal women with HSDD, 50.2% had arousal problems, 42.5% lubrication problems, 39.0% combination, and 46.2% neither. Among 174 postmenopausal women, prevalence percentages were 58.0% arousal, 56.9% lubrication, 49.4% combined, and 34.5% neither. The strongest predictor of combined arousal/lubrication problems was self-reported severity of HSDD. Among premenopausal women, race/ethnicity, depression, and lower relationship happiness were also associated with combined arousal/lubrication problems. Among postmenopausal women, surgical menopause and use of selective serotonin reuptake inhibitors were positively associated with arousal problems. Arousal and lubrication problems were present in approximately half of this subsample of HSDD Registry participants, with distinctions in prevalence and predictors by menopausal status and type of arousal difficulty (arousal vs. lubrication). C1 [Maserejian, Nancy N.; Huang, Liyuan; Rosen, Raymond C.] New England Res Inst Inc, Dept Epidemiol, Watertown, MA 02472 USA. [Shifren, Jan] Massachusetts Gen Hosp, Vincent OB GYN Serv, Boston, MA 02114 USA. [Parish, Sharon J.] Montefiore Med Ctr, Albert Einstein Coll Med, Dept Med, Bronx, NY 10467 USA. [Segraves, R. Taylor] Case Western Reserve Univ, Dept Pathol, Metrohlth Med Ctr, Cleveland, OH 44106 USA. RP Maserejian, NN (reprint author), New England Res Inst Inc, Dept Epidemiol, 9 Galen St, Watertown, MA 02472 USA. EM nmaserjian@neriscience.com NR 34 TC 13 Z9 14 U1 0 U2 1 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 0092-623X J9 J SEX MARITAL THER JI J. Sex Marital Ther. PY 2012 VL 38 IS 1 BP 41 EP 62 DI 10.1080/0092623X.2011.569642 PG 22 WC Psychology, Clinical; Family Studies SC Psychology; Family Studies GA 917MM UT WOS:000302181500003 PM 22268981 ER PT J AU Zhai, RH Zhao, Y Su, L Cassidy, L Liu, G Christiani, DC AF Zhai, Rihong Zhao, Yang Su, Li Cassidy, Lauren Liu, Geoffrey Christiani, David C. TI Genome-wide DNA Methylation Profiling of Cell-Free Serum DNA in Esophageal Adenocarcinoma and Barrett Esophagus SO NEOPLASIA LA English DT Article ID LUNG-CANCER PATIENTS; K-RAS MUTATIONS; FREE PLASMA DNA; PROMOTER METHYLATION; NEOPLASTIC PROGRESSION; ABERRANT METHYLATION; COLORECTAL-CANCER; GASTRIC CARDIA; PROTEIN GENES; RISK AB Aberrant DNA methylation (DNAm) is a feature of most types of cancers. Genome-wide DNAm profiling has been performed successfully on tumor tissue DNA samples. However, the invasive procedure limits the utility of tumor tissue for epidemiological studies. While recent data indicate that cell-free circulating DNAm (cfDNAm) profiles reflect DNAm status in corresponding tumor tissues, no studies have examined the association of cfDNAm with cancer or precursors on a genome-wide scale. The objective of this pilot study was to evaluate the putative significance of genome-wide cfDNAm profiles in esophageal adenocarcinoma (EA) and Barrett esophagus (BE, EA precursor). We performed genome-wide DNAm profiling in EA tissue DNA (n = 8) and matched serum DNA (n = 8), in serum DNA of BE (n = 10), and in healthy controls (n = 10) using the Infinium HumanMethylation27 BeadChip that covers 27,578 CpG loci in 14,495 genes. We found that cfDNAm profiles were highly correlated to DNAm profiles in matched tumor tissue DNA (r = 0.92) in patients with EA. We selected the most differentially methylated loci to perform hierarchical clustering analysis. We found that 911 loci can discriminate perfectly between EA and control samples, 554 loci can separate EA from BE samples, and 46 loci can distinguish BE from control samples. These results suggest that genome-wide cfDNAm profiles are highly consistent with DNAm profiles detected in corresponding tumor tissues. Differential cfDNAm profiling may be a useful approach for the noninvasive screening of EA and EA premalignant lesions. C1 [Zhai, Rihong; Zhao, Yang; Su, Li; Cassidy, Lauren; Christiani, David C.] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Environm & Occupat Med & Epidemiol Program, Boston, MA 02115 USA. [Liu, Geoffrey] Univ Toronto, Ontario Canc Inst, Princess Margaret Hosp, Dept Med, Toronto, ON M5S 1A1, Canada. [Christiani, David C.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. RP Christiani, DC (reprint author), Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Environm & Occupat Med & Epidemiol Program, 665 Huntington Ave,FXB109, Boston, MA 02115 USA. EM rzhai@hsph.harvard.edu; dchris@hsph.harvard.edu RI Liu, Geoffrey/N-4421-2016 FU National Institutes of Health [RO1CA109193, RO3CA110822, RO1CA074386, P50CA090578, ES00002]; Flight Attendant Medical Research Institute [YCSA-062459] FX This study was funded by National Institutes of Health grant RO1CA109193, RO3CA110822, RO1CA074386, P50CA090578, and ES00002 and by the Flight Attendant Medical Research Institute Award YCSA-062459. All authors disclosed no conflict of interest; the institutes that provided the grant supports did not participate in the study design, the collection, analysis, or interpretation of data. NR 44 TC 22 Z9 24 U1 1 U2 11 PU NEOPLASIA PRESS PI ANN ARBOR PA 1150 W MEDICAL CENTER DR, MSRB III, RM 9303, ANN ARBOR, MI 48109-0648 USA SN 1522-8002 J9 NEOPLASIA JI Neoplasia PD JAN PY 2012 VL 14 IS 1 BP 29 EP U39 DI 10.1593/neo.111626 PG 6 WC Oncology SC Oncology GA 922HJ UT WOS:000302537700003 PM 22355271 ER PT J AU Byers, AL Arean, PA Yaffe, K AF Byers, Amy L. Arean, Patricia A. Yaffe, Kristine TI Low Use of Mental Heat Services Among Older Americans With Mood and Anxiety Disorders SO PSYCHIATRIC SERVICES LA English DT Article ID COMORBIDITY-SURVEY-REPLICATION; WORLD-HEALTH-ORGANIZATION; RANDOMIZED CONTROLLED-TRIAL; REDUCING SUICIDAL IDEATION; PRIMARY-CARE PATIENTS; LATE-LIFE DEPRESSION; UNITED-STATES; NCS-R; FUTURE-RESEARCH; ADULTS AB Objective: It is unclear why late-life mood and anxiety disorders are highly undertreated, despite being common among older adults. Thus this study examined prevalence of and key factors associated with nonuse of mental health services among older community-dwelling adults with these disorders. Methods: The sample included 348 participants aged 55 years or older who met 12-month criteria for DSM-IV mood and anxiety disorders and responded to the National Comorbidity Survey Replication (NCS-R), a population-based probability sample. Analyses included frequency measures and logistic regression with weights and complex design corrected statistical tests. Key factors associated with not using mental health services were determined in a final multivariable model based on a systematic approach that accounted for a comprehensive list of potential predictors. Results: Approximately 70% of older adults with mood and anxiety disorders did not use services. Those who were from racial-ethnic minority groups, were not comfortable with discussing personal problems, were married or cohabitating, and had middle- versus high-income status had increased odds of not using mental health services. In addition, respondents with mild versus serious disorders, no chronic pain complaints, and low versus high perceived cognitive impairment had greater odds of nonuse. Conclusions: Results indicate that improvements are needed in the following areas to combat the very high number of mood and anxiety disorders that go untreated in older Americans: awareness of need, comfort in discussing personal problems with a health care professional, and screening and other prevention efforts. (Psychiatric Services 63:66-72, 2012) C1 [Byers, Amy L.; Arean, Patricia A.; Yaffe, Kristine] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94121 USA. [Yaffe, Kristine] Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94121 USA. [Yaffe, Kristine] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94121 USA. [Yaffe, Kristine] San Francisco VA Med Ctr, Mental Hlth Res Serv, San Francisco, CA USA. RP Byers, AL (reprint author), Univ Calif San Francisco, Dept Psychiat, 4150 Clement St,116H, San Francisco, CA 94121 USA. EM amy.byers@ucsf.edu FU National Institute of Mental Health [MH079093, MH074717, U01-MH60220]; National Institute on Aging [AG031155]; Substance Abuse and Mental Health Services Administration [044708]; Robert Wood Johnson Foundation; John W. Alden Trust FX This work was supported by grants MH079093 and MH074717 from the National Institute of Mental Health and by grant AG031155 from the National Institute on Aging. The NCS-R was supported by grant U01-MH60220 from the National Institute of Mental Health, with supplemental support from the National Institute on Drug Abuse, the Substance Abuse and Mental Health Services Administration, grant 044708 by the Robert Wood Johnson Foundation, and the John W. Alden Trust. The views and opinions expressed in this report are those of the authors and should not be construed otherwise. NR 53 TC 27 Z9 27 U1 2 U2 8 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 1075-2730 J9 PSYCHIAT SERV JI Psychiatr. Serv. PD JAN PY 2012 VL 63 IS 1 BP 66 EP 72 PG 7 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychiatry SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychiatry GA 917NP UT WOS:000302184900013 PM 22227762 ER PT J AU Thompson-Brenner, H Satir, DA Franko, DL Herzog, DB AF Thompson-Brenner, Heather Satir, Dana A. Franko, Debra L. Herzog, David B. TI Clinician Reactions to Patients With Eating Disorders: A Review of the Literature SO PSYCHIATRIC SERVICES LA English DT Review ID HEALTH-CARE PROFESSIONALS; ANOREXIA-NERVOSA; BULIMIA-NERVOSA; THERAPEUTIC ALLIANCE; ATTITUDES; COUNTERTRANSFERENCE; MORTALITY; KNOWLEDGE; STIGMA; PSYCHOTHERAPY AB Objective: The delivery of psychiatric services may be affected by clinicians' negative reactions to treatment-resistant or stigmatized patient groups. Some research has found that clinicians across professional disciplines react negatively to patients with eating disorders, but empirical data related to this topic have not been systematically reviewed. The authors sought to review all published empirical studies of clinician reactions to patients with eating disorders in order to characterize negative reactions to these patients and identify patient or clinical factors associated with negative reactions. Methods: The authors conducted a comprehensive online search for all published studies of clinician reactions in regard to patients with eating disorders. The reference lists of articles found in the literature search were examined to identify additional studies. Results: Twenty studies, published between 1984 and 2010, were found. Clinician negative reactions in regard to patients with eating disorders typically reflected frustration, hopelessness, lack of competence, and worry. Inexperienced clinicians appeared to hold more negative attitudes toward patients with eating disorders than toward other patient groups, but experienced psychotherapists did not experience strong negative reactions to patients with eating disorders. Medical practitioners consistently reported strong feelings of lack of competence in treating eating disorders. Negative reactions to patients with eating disorders were associated with patients' lack of improvement and personality pathology and with clinicians' stigmatizing beliefs, inexperience, and gender. Conclusions: Research about the impact of negative clinician attitudes toward patients with eating disorders on psychiatric service delivery, including multivariate analyses using larger samples, comparison groups, validated instruments, and experimental methods, is much needed. (Psychiatric Services 63:73-78,2012) C1 [Thompson-Brenner, Heather] Boston Univ, Dept Psychol, Ctr Anxiety & Related Disorders, Boston, MA 02215 USA. [Franko, Debra L.] Northeastern Univ, Dept Counseling & Appl Educ Psychol, Boston, MA 02115 USA. [Herzog, David B.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Herzog, David B.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Thompson-Brenner, H (reprint author), Boston Univ, Dept Psychol, Ctr Anxiety & Related Disorders, 648 Beacon St, Boston, MA 02215 USA. EM heatherthompsonbrenner@gmail.com FU Harris Center for Education and Advocacy in Eating Disorders; National Institute of Mental Health [K23 MH071641-01A2] FX This work was supported by the Harris Center for Education and Advocacy in Eating Disorders and by grant K23 MH071641-01A2 from the National Institute of Mental Health. NR 43 TC 15 Z9 16 U1 1 U2 12 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 1075-2730 J9 PSYCHIAT SERV JI Psychiatr. Serv. PD JAN PY 2012 VL 63 IS 1 BP 73 EP 78 PG 6 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychiatry SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychiatry GA 917NP UT WOS:000302184900014 PM 22227763 ER PT J AU Oaklander, AL AF Oaklander, Anne Louise TI Common Neuropathic Itch Syndromes SO ACTA DERMATO-VENEREOLOGICA LA English DT Review DE itch; pruritus; diagnosis; herpes zoster; radiculopathy; peripheral nerve ID TRIGEMINAL TROPHIC SYNDROME; TOXIN TYPE-A; SYMMETRIC POLYNEUROPATHY ROLE; PRACTICE PARAMETER EVALUATION; POSITRON-EMISSION-TOMOGRAPHY; REGIONAL PAIN SYNDROME; HISTAMINE-INDUCED ITCH; NOTALGIA PARESTHETICA; BRACHIORADIAL PRURITUS; HERPES-ZOSTER AB Patients with chronic itch are diagnosed and treated by dermatologists. However, itch is a neural sensation and some forms of chronic itch are the presenting symptoms of neurological diseases. Dermatologists need some familiarity with the most common neuropathic itch syndromes to initiate diagnostic testing and to know when to refer to a neurologist. This review summarizes current knowledge, admittedly incomplete, on neuropathic itch caused by diseases of the brain, spinal cord, cranial or spinal nerve-roots, and peripheral nerves. C1 [Oaklander, Anne Louise] Massachusetts Gen Hosp, Dept Neurol, Nerve Injury Unit, Boston, MA 02114 USA. [Oaklander, Anne Louise] Massachusetts Gen Hosp, Dept Pathol, Nerve Injury Unit, Boston, MA 02114 USA. RP Oaklander, AL (reprint author), Massachusetts Gen Hosp, Dept Neurol, Nerve Injury Unit, 275 Charles St,Warren 310, Boston, MA 02114 USA. EM aoaklan-der@partners.org FU NIH (NINDS) [K24 NS059892]; National Institutes of Health; Department of Defense FX Supported in part by the NIH (NINDS K24 NS059892).; Dr. Oaklander receives research support from the National Institutes of Health, the Department of Defense, and several family foundations. She serves on the editorial boards of PAIN, Neurology Today, and Pain Research Forum. She is a member of the Scientific Advisory Board of the RSD Syndrome Association. NR 60 TC 18 Z9 18 U1 0 U2 8 PU ACTA DERMATO-VENEREOLOGICA PI UPPSALA PA TRADGARDSGATAN 14, UPPSALA, SE-753 09, SWEDEN SN 0001-5555 J9 ACTA DERM-VENEREOL JI Acta Derm.-Venereol. PY 2012 VL 92 IS 2 BP 118 EP 125 DI 10.2340/00015555-1318 PG 8 WC Dermatology SC Dermatology GA 912TQ UT WOS:000301823400002 PM 22307048 ER PT J AU Caplan, D Waters, G Howard, D AF Caplan, David Waters, Gloria Howard, David TI Slave systems in verbal short-term memory SO APHASIOLOGY LA English DT Article DE Aphasia; Aphasiology; Neuropsychology; Psychosocial; Language; Brain ID IMMEDIATE SERIAL-RECALL; STIMULUS SET SPECIFICITY; WORD-LENGTH; IRRELEVANT SPEECH; WORKING-MEMORY; PHONOLOGICAL SIMILARITY; ARTICULATORY SUPPRESSION; LEXICAL ACCESS; CONDUCTION APHASIA; UNATTENDED SPEECH AB Background: The model of performance in short-termmemory (STM) tasks that has been most influential in cognitive neuropsychological work on deficits of STM is the "working memory" model mainly associated with the work of Alan Baddeley and his colleagues. Aim: This paper reviews the model. We examine the development of this theory in studies that account for STM performances in normal (non-brain-damaged) individuals, and then review the application of this theory to neuropsychological cases and specifications, modifications, and extensions of the theory that have been suggested on the basis of these cases. Our approach is to identify the major phenomena that have been discussed and to examine selected papers dealing with those phenomena in some detail. Main Contribution: The main contribution is a review of the WM model that includes both normative and neuropsychological data. Conclusions: We conclude that the WM model has many inconsistencies and empirical inadequacies, and that cognitive neuropsychologists might benefit from considering other models when they attempt to describe and explain patients' performances on STM tasks. C1 [Caplan, David] Massachusetts Gen Hosp, Dept Neurol, Neuropsychol Lab, Boston, MA 02114 USA. [Waters, Gloria] Boston Univ, Sargent Coll, Dept Speech & Hearing Sci, Boston, MA 02215 USA. [Howard, David] Newcastle Univ, Sch Educ Commun & Language Sci, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England. RP Caplan, D (reprint author), Massachusetts Gen Hosp, Dept Neurol, Neuropsychol Lab, 175 Cambridge St,Suite 340, Boston, MA 02114 USA. EM dcaplan@partners.org NR 169 TC 7 Z9 7 U1 6 U2 32 PU PSYCHOLOGY PRESS PI HOVE PA 27 CHURCH RD, HOVE BN3 2FA, EAST SUSSEX, ENGLAND SN 0268-7038 J9 APHASIOLOGY JI Aphasiology PY 2012 VL 26 IS 3-4 SI SI BP 279 EP 316 DI 10.1080/02687038.2011.642795 PG 38 WC Clinical Neurology SC Neurosciences & Neurology GA 910OT UT WOS:000301649800003 ER PT J AU Liu, J Cristea, MC Frankel, P Neuhausen, SL Steele, L Engelstaedter, V Matulonis, U Sand, S Tung, N Garber, JE Weitzel, JN AF Liu, Joyce Cristea, Mihaela C. Frankel, Paul Neuhausen, Susan L. Steele, Linda Engelstaedter, Verena Matulonis, Ursula Sand, Sharon Tung, Nadine Garber, Judy E. Weitzel, Jeffrey N. TI Clinical characteristics and outcomes of BRCA-associated ovarian cancer: genotype and survival SO CANCER GENETICS LA English DT Article DE BRCA1; BRCA2; ovarian carcinoma; genetics; cancer ID GERM-LINE MUTATIONS; WOMEN; CARCINOMA; FEATURES; BREAST; CHEMOTHERAPY; RESISTANCE; SENSITIVITY; POLYMERASE; CARRIERS AB Previous studies have suggested that BRCA-related epithelial ovarian cancer (EOC) conveys improved survival compared with that of sporadic EOC, but few studies have evaluated differences between BRCA genotypes. We compared characteristics and outcome by genotype in BRCA-associated EOC. Patients with BRCA-associated EOC who were diagnosed between January 30,1981, and December 30, 2008, were retrospectively identified through institutional review board approved registry studies. We examined clinical characteristics, including event-free survival (EFS) and overall survival (OS), for BRCA1 versus BRCA2 patients. We identified 197 cases (148 BRCA1 cases; 49 BRCA2 cases); the median follow-up period was 63 months. BRCA2 patients were older (55.4 vs. 51.1 y; P < 0.01) and had fewer poorly differentiated tumors (67% vs. 82%; P < 0.05). No difference in EFS was observed. OS at 5 years was 75% in BRCA2 patients versus 61% in BRCA1 patients; this was not statistically significant. A non-significant trend toward improved OS was observed in BRCA2 patients with advanced-stage disease (hazard ratio = 0.59; 95% confidence interval 0.32-1.08). Age and grade differed significantly between BRCA1 and BRCA2 carriers in our study population. Whereas no overall differences in EFS or OS were observed, there was a trend toward improved OS in BRCA2 carriers with advanced-stage disease. This may reflect important differences between BRCA genotypes and should be validated in larger studies. C1 [Cristea, Mihaela C.; Weitzel, Jeffrey N.] City Hope Natl Med Ctr, Dept Med Oncol, Duarte, CA 91010 USA. [Liu, Joyce; Engelstaedter, Verena; Matulonis, Ursula; Garber, Judy E.] Dana Farber Partners CancerCare, Dept Med Oncol, Boston, MA USA. [Frankel, Paul] City Hope Natl Med Ctr, Div Informat Sci, Duarte, CA USA. [Neuhausen, Susan L.; Steele, Linda] City Hope Natl Med Ctr, Dept Populat Sci, Beckman Res Inst, Duarte, CA USA. [Sand, Sharon; Weitzel, Jeffrey N.] City Hope Natl Med Ctr, Div Clin Canc Genet, Duarte, CA USA. [Tung, Nadine] Beth Israel Deaconess Med Ctr, Dept Med, Canc Risk & Prevent Program, Boston, MA 02215 USA. RP Weitzel, JN (reprint author), City Hope Natl Med Ctr, Dept Med Oncol, Duarte, CA 91010 USA. EM jweitzel@coh.org FU Markel Foundation; National Cancer Institute [RC4CA153828]; Dana-Farber/Harvard Cancer Center SPORE in Breast Cancer; Friends of Dana-Farber; National Institutes of Health [R01CA074415]; Morris and Horowitz Families Endowed Professorship FX The research described was supported in part by the Markel Foundation; by Award Number RC4CA153828 (to JNW) from the National Cancer Institute (the content is solely the responsibility of the authors and does not necessarily represent the official views of the National Cancer Institute or the National Institutes of Health); by the Dana-Farber/Harvard Cancer Center SPORE in Breast Cancer (to JEG); and by the Friends of Dana-Farber (to JL). Support was also received from Award Number R01CA074415 (to SLN) from the National Institutes of Health, and from the Morris and Horowitz Families Endowed Professorship (to SLN). NR 42 TC 9 Z9 10 U1 2 U2 8 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 2210-7762 J9 CANCER GENET-NY JI Cancer Genet. PD JAN-FEB PY 2012 VL 205 IS 1-2 BP 34 EP 41 DI 10.1016/j.cancergen.2012.01.008 PG 8 WC Oncology; Genetics & Heredity SC Oncology; Genetics & Heredity GA 916PB UT WOS:000302114600005 PM 22429596 ER PT J AU Wisneski, AD Azadani, AN Matthews, PB Chitsaz, S Guccione, JM Ge, L Tseng, EE AF Wisneski, A. D. Azadani, A. N. Matthews, P. B. Chitsaz, S. Guccione, J. M. Ge, L. Tseng, E. E. TI A Quantitative Approach to Pulmonary Autograft Remodeling After the Ross Procedure SO CARDIOLOGY LA English DT Meeting Abstract C1 Univ Calif San Francisco, Dept Surg, San Francisco, CA USA. San Francisco VA Med Ctr, Dept Surg, San Francisco, CA USA. RI Chitsaz, Sam/C-4586-2008 NR 0 TC 0 Z9 0 U1 0 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0008-6312 J9 CARDIOLOGY JI Cardiology PY 2012 VL 121 IS 2 BP 144 EP 144 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 916WL UT WOS:000302133800122 ER PT J AU Forster, A Gass, A Kern, R Ay, H Chatzikonstantinou, A Hennerici, MG Szabo, K AF Foerster, A. Gass, A. Kern, R. Ay, H. Chatzikonstantinou, A. Hennerici, M. G. Szabo, K. TI Brain Imaging in Patients with Transient Ischemic Attack: A Comparison of Computed Tomography and Magnetic Resonance Imaging SO EUROPEAN NEUROLOGY LA English DT Article DE Transient ischemic attack; TIA; CT; MRI ID DIFFUSION-WEIGHTED MRI; CEREBRAL-ISCHEMIA; ACUTE-PHASE; STROKE; DEFINITION; CT AB Background: Brain imaging in stroke aims at the detection of the relevant ischemic tissue pathology. Cranial computed tomography (CT) is frequently used in patients with transient ischemic attack (TIA) but no data is available on how it directly compares to magnetic resonance imaging (MRI). Methods: We compared detection of acute ischemic lesions on CT and MRI in 215 consecutive TIA patients who underwent brain imaging with either CT (n = 161) or MRI (n = 54). An MRI was performed within 24 h in all patients who had CT initially. Results: An initial assessment with CT revealed no acute pathology in 154(95.7%) and possible acute infarction in 7 (4.3%) patients. The acute infarct on CT was confirmed by diffusion-weighted imaging (DWI) in only 2 cases (28.6%). DWI detected an acute infarct in 50 of the 154 patients with normal baseline CT (32.5%). Among 54 patients without baseline CT, DWI showed acute ischemic lesions in 19(35.2%). The ischemic lesions had a median volume of 0.87 cm(3) (range: 0.08-15.61), and the lesion pattern provided clues to the underlying etiology in 13.7%. Conclusion: Acute MRI is advantageous over CT to confirm the probable ischemic nature and to identify the etiology in TIA patients. Copyright (C) 2012 S. Karger AG, Basel C1 [Foerster, A.] Univ Heidelberg, Univ Med Mannheim, Dept Neurol, Univ Klinikum Mannheim, DE-68167 Mannheim, Germany. [Ay, H.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Boston, MA USA. [Ay, H.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA USA. RP Forster, A (reprint author), Univ Heidelberg, Univ Med Mannheim, Dept Neurol, Univ Klinikum Mannheim, Theodor Kutzer Ufer 1-3, DE-68167 Mannheim, Germany. EM foerster@neuro.ma.uni-heidelberg.de FU NIH [R01-NS059710] FX The authors have no conflict of interest related to the present study. Dr. Ay has been supported by NIH grant R01-NS059710. NR 13 TC 13 Z9 15 U1 0 U2 11 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0014-3022 J9 EUR NEUROL JI Eur. Neurol. PY 2012 VL 67 IS 3 BP 136 EP 141 DI 10.1159/000333286 PG 6 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 914PM UT WOS:000301963600002 PM 22261538 ER PT J AU Won, SH Lu, Q Bertram, L Tanzi, RE Lange, C AF Won, Sungho Lu, Qing Bertram, Lars Tanzi, Rudolph E. Lange, Christoph TI On the Meta-Analysis of Genome-Wide Association Studies: A Robust and Efficient Approach to Combine population and Family-Based Studies SO HUMAN HEREDITY LA English DT Article DE Meta-analysis; Genome-wide study; Population stratification ID UNIFIED APPROACH; GENETIC ASSOCIATION; ALZHEIMERS-DISEASE; IMPUTATION; TESTS; INFERENCE; LOCI; STRATIFICATION; APOE AB For the meta-analysis of genome-wide association studies, we propose a new method to adjust for the population stratification and a linear mixed approach that combines family-based and unrelated samples. The proposed approach achieves similar power levels as a standard meta-analysis which combines the different test statistics or p values across studies. However, by virtue of its design, the proposed approach is robust against population admixture and stratification, and no adjustments for population admixture and stratification, even in unrelated samples, are required. Using simulation studies, we examine the power of the proposed method and compare it to standard approaches in the meta-analysis of genome-wide association studies. The practical features of the approach are illustrated with a meta-analysis of three genome-wide association studies for Alzheimer's disease. We identify three single nucleotide polymorphisms showing significant genome-wide association with affection status. Two single nucleotide polymorphisms are novel and will be verified in other populations in our follow-up study. Copyright (C) 2012S. Karger AG, Basel C1 [Won, Sungho] Chung Ang Univ, Dept Appl Stat, Seoul 156756, South Korea. [Won, Sungho] Chung Ang Univ, Res Ctr Data Sci, Seoul 156756, South Korea. [Lu, Qing] Michigan State Univ, Dept Epidemiol, E Lansing, MI 48824 USA. [Bertram, Lars; Tanzi, Rudolph E.] Massachusetts Gen Hosp, Dept Neurol, Genet & Aging Res Unit, Charlestown, MA USA. [Bertram, Lars] Max Planck Inst Mol Genet, Dept Vertebrate Gen, Neuropsychiat Genet Grp, D-14195 Berlin, Germany. [Lange, Christoph] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Lange, Christoph] Harvard Univ, Sch Med, Boston, MA USA. [Lange, Christoph] Brigham & Womens Hosp, Ctr Genom Med, Boston, MA 02115 USA. [Lange, Christoph] Univ Bonn, Inst Genom Math, Bonn, Germany. [Lange, Christoph] German Ctr Neurodegenerat Dis DZNE, Bonn, Germany. RP Won, SH (reprint author), Chung Ang Univ, Dept Appl Stat, Seoul 156756, South Korea. EM swon@cau.ac.kr RI Bertram, Lars/K-3889-2015 OI Bertram, Lars/0000-0002-0108-124X FU National Research Foundation of Korea; Korean Government [2010-0023594]; Industrial Strategic Technology Development Program [10040176]; Ministry of Knowledge Economy (MKE, Korea); NIMH [1R37MH60009]; Cure Alzheimer's Fund FX This work was supported by National Research Foundation of Korea Grant funded by the Korean Government 2010-0023594, and by the Industrial Strategic Technology Development Program (10040176) funded by the Ministry of Knowledge Economy (MKE, Korea). Also this work was supported by the NIMH 1R37MH60009 and Cure Alzheimer's Fund. The authors would like to thank the anonymous referees for their helpful suggestions and comments. NR 36 TC 3 Z9 3 U1 0 U2 2 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0001-5652 J9 HUM HERED JI Hum. Hered. PY 2012 VL 73 IS 1 BP 35 EP 46 DI 10.1159/000331219 PG 12 WC Genetics & Heredity SC Genetics & Heredity GA 916NS UT WOS:000302111100006 PM 22261799 ER PT J AU Lang, HJ Huang, XD Yang, YL AF Lang, Haijing Huang, Xudong Yang, Yongliang TI Identification of Putative Molecular Imaging Probes for BACE-1 by Accounting for Protein Flexibility in Virtual Screening SO JOURNAL OF ALZHEIMERS DISEASE LA English DT Article DE Alzheimer's disease; BACE; MICAD; PET probes; protein flexibility; receptor ensemble; virtual screening ID DRUG DESIGN; RECEPTOR FLEXIBILITY; LIGAND DOCKING; CONFORMATIONS; INHIBITORS; DISCOVERY; DISEASE; PET AB beta-secretase (BACE-1), an enzyme critical in the process of amyloid-beta (A beta) peptides deposition in human brain, is closely associated with the onset and progression of Alzheimer's disease (AD). A strong need exists, therefore, to identify molecular imaging probes homing at BACE-1 for use with positron emission tomography (PET) that is recognized as an effective tool for detecting AD. Through this imaging, an early diagnosis of AD could be made. Herein, to identify suitable molecular probes for use with PET, we searched the Molecular Imaging and Contrast Agent Database (MICAD), an online database warehousing scientific information regarding molecular imaging and contrast agents, and applied a virtual screening approach against the different confirmations of BACE-1 obtained from the World Wide Protein Database. The lack of considering receptor flexibility is a key drawback in virtual screening for drug discovery. Therefore, we incorporated protein flexibility into the virtual screening by using an ensemble of 143 experimental BACE-1 structures derived from the Protein Data Bank. Finally, the best performing affinity was recorded and used in the ranking of each ligand. To the best of our knowledge, this is the first virtual screening approach used to identify four new molecular probes that could target BACE-1 with favorable affinity, a discovery that can lead to the development of new PET probes for the early detection and therapy of AD. However, the actual utility of these probes can only be ascertained after in vitro and in vivo investigations. C1 [Lang, Haijing; Yang, Yongliang] Dalian Univ Technol, Ctr Mol Med, Sch Life Sci & Biotechnol, Dalian 116023, Peoples R China. [Huang, Xudong] Brigham & Womens Hosp, Dept Radiol, Conjugate & Med Chem Lab, Div Nucl Med & Mol Imaging, Boston, MA 02115 USA. [Huang, Xudong] Harvard Univ, Sch Med, Boston, MA USA. [Huang, Xudong] Massachusetts Gen Hosp, Dept Psychiat, Neurochem Lab, Boston, MA 02114 USA. RP Yang, YL (reprint author), Dalian Univ Technol, Ctr Mol Med, Sch Life Sci & Biotechnol, Dalian 116023, Peoples R China. EM xhuang3@partners.org; everbright99@gmail.com FU Fundamental Research Funds for the Central Universities [DUT11SM12]; National Science Foundation in China, Medical Board Oncology Department [81000975]; Radiology Department of Brigham and Women's Hospital (BWH) FX Work in the Y. Yang laboratory was supported by the Fundamental Research Funds for the Central Universities (grant: DUT11SM12) and National Science Foundation in China, Medical Board Oncology Department (grant: 81000975); Work in the X. Huang laboratory was supported by the research funds from Radiology Department of Brigham and Women's Hospital (BWH). NR 24 TC 3 Z9 3 U1 1 U2 11 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 1387-2877 J9 J ALZHEIMERS DIS JI J. Alzheimers Dis. PY 2012 VL 29 IS 2 BP 351 EP 359 DI 10.3233/JAD-2011-111787 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 916SV UT WOS:000302124400010 PM 22232010 ER PT J AU Biswas, A Petnicki-Ocwieja, T Kobayashi, KS AF Biswas, Amlan Petnicki-Ocwieja, Tanja Kobayashi, Koichi S. TI Nod2: a key regulator linking microbiota to intestinal mucosal immunity SO JOURNAL OF MOLECULAR MEDICINE-JMM LA English DT Review DE NLR proteins; Nod2; Commensal microflora; Crohn's disease; Paneth cells ID INFLAMMATORY-BOWEL-DISEASE; NF-KAPPA-B; ILEAL CROHNS-DISEASE; ALPHA-DEFENSIN EXPRESSION; TOLL-LIKE RECEPTORS; MURAMYL DIPEPTIDE; EPITHELIAL-CELLS; PANETH CELLS; PYRIN DOMAIN; MAINTAIN HOMEOSTASIS AB The human intestine harbors a large number of bacteria that are constantly interacting with the intestinal immune system, eliciting non-pathological basal level immune responses. Increasing evidence points to dysbiosis of microbiota in the intestine as an underlying factor in inflammatory bowel disease susceptibility. Loss-of-function mutations in NOD2 are among the stronger genetic factors linked to ileal Crohn's disease. Indeed, Nod2 is a key regulator of microbiota in the intestine, as microflora in the terminal ileum is dysregulated in Nod2-deficient mice. Nod2 is highly expressed in Paneth cells, which are responsible for the regulation of ileal microflora by antimicrobial compounds, and Nod2-deficient ileal intestinal epithelia are unable to kill bacteria efficiently. It is therefore likely that NOD2 mutations in Crohn's disease may increase disease susceptibility by altering interactions between ileal microbiota and mucosal immunity. C1 [Biswas, Amlan; Petnicki-Ocwieja, Tanja; Kobayashi, Koichi S.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02215 USA. [Biswas, Amlan; Petnicki-Ocwieja, Tanja; Kobayashi, Koichi S.] Harvard Univ, Sch Med, Dept Microbiol & Immunobiol, Boston, MA 02215 USA. RP Kobayashi, KS (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Dana 1420A,450 Brookline Ave, Boston, MA 02215 USA. EM Koichi_Kobayashi@dfci.harvard.edu FU NIH [R01DK074738]; Crohn's and Colitis Foundation of America; Cancer Research Institute; Claudia Adams Barr Award FX The authors thank Yuen-Joyce Liu for critical reading. This work was supported by grants from the NIH (K.S.K. R01DK074738) and the Crohn's and Colitis Foundation of America (K.S.K.). K.S.K. is a recipient of the Investigator Award from the Cancer Research Institute and the Claudia Adams Barr Award. NR 91 TC 36 Z9 38 U1 1 U2 15 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0946-2716 J9 J MOL MED JI J. Mol. Med. PD JAN PY 2012 VL 90 IS 1 BP 15 EP 24 DI 10.1007/s00109-011-0802-y PG 10 WC Genetics & Heredity; Medicine, Research & Experimental SC Genetics & Heredity; Research & Experimental Medicine GA 916WX UT WOS:000302135000003 PM 21861185 ER PT J AU McFarland, LV Raugi, GJ Taylor, LL Reiber, GE AF McFarland, Lynne V. Raugi, Greg J. Taylor, Leslie L. Reiber, Gayle E. TI Implementation of an education and skills programme in a teledermatology project for rural veterans SO JOURNAL OF TELEMEDICINE AND TELECARE LA English DT Article ID CONSULT SYSTEM; CARE; DERMATOLOGY; WORKFORCE AB In July 2009 we implemented a store-and-forward teledermatology project to provide dermatology care to veterans living in underserved rural areas of the Pacific Northwest region of the US. We also developed an educational programme for rural primary care providers and imaging technicians. Participants were tested and their competencies were assessed at baseline and during a two-year project. Participation in a comprehensive education programme improved the knowledge of dermatology diagnosis and treatment care plans. All of the providers were performing dermatology procedures (e.g. biopsies, excisions, cauteries) after two years and more patients were being seen at their rural clinics than when the teledermatology project began (85% vs 39%). After two years, 71% of the providers and 56% of the imaging technicians had completed surgical training sessions and all passed their competency assessments. The educational component of the teledermatology project created teams of primary care health-care providers and imaging technicians with improved dermatology educational levels and new dermatology skills. C1 [McFarland, Lynne V.; Taylor, Leslie L.; Reiber, Gayle E.] VA Puget Sound Hlth Care Syst, Dept Vet Affairs, Seattle, WA 98101 USA. [McFarland, Lynne V.] Univ Washington, Dept Med Chem, Seattle, WA 98195 USA. [Raugi, Greg J.] VA Puget Sound Hlth Care Syst, Div Dermatol, Seattle, WA 98101 USA. [Raugi, Greg J.] Univ Washington, Dept Med, Seattle, WA USA. [Reiber, Gayle E.] Univ Washington, Dept Hlth Serv & Epidemiol, Seattle, WA 98195 USA. RP McFarland, LV (reprint author), VA Puget Sound Hlth Care Syst, Dept Vet Affairs, 1100 Olive Way,Suite 1400, Seattle, WA 98101 USA. EM Lynne.McFarland@va.gov FU US Department of Veterans Affairs; VISN 20 Office of Rural Health Services; VA Health Services Research and Development FX The work was funded by the US Department of Veterans Affairs, the VISN 20 Office of Rural Health Services and VA Health Services Research and Development. Parts of the work were presented at the VISN20 Teledermatology Summer Conferences, Seattle, WA, 14 June 2010 and 13 June 2011 and at the HSR&D National Meeting, National Harbor, MA, 16 February 2011. 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 16 TC 10 Z9 10 U1 0 U2 0 PU ROYAL SOC MEDICINE PRESS LTD PI LONDON PA 1 WIMPOLE STREET, LONDON W1G 0AE, ENGLAND SN 1357-633X J9 J TELEMED TELECARE JI J. Telemed. Telecare PY 2012 VL 18 IS 2 BP 66 EP 71 DI 10.1258/jtt.2011.110518 PG 6 WC Health Care Sciences & Services SC Health Care Sciences & Services GA 912PE UT WOS:000301811300002 PM 22198956 ER PT J AU Choi, K Kim, JY Ahn, JH Choi, JM Im, M Choi, YK AF Choi, Kyungyong Kim, Jee-Yeon Ahn, Jae-Hyuk Choi, Ji-Min Im, Maesoon Choi, Yang-Kyu TI Integration of field effect transistor-based biosensors with a digital microfluidic device for a lab-on-a-chip application SO LAB ON A CHIP LA English DT Article ID ELECTRICAL DETECTION; PLURONIC ADDITIVES; MASS-SPECTROMETRY; MALDI-MS; DROPLETS AB A new platform for lab-on-a-chip system is suggested that utilizes a biosensor array embedded in a digital microfluidic device. With field effect transistor (FET)-based biosensors embedded in the middle of droplet-driving electrodes, the proposed digital microfluidic device can electrically detect avian influenza antibody (anti-AI) in real time by tracing the drain current of the FET-based biosensor without a labeling process. Digitized transport of a target droplet enclosing anti-AI from an inlet to the embedded sensor is enabled by the actuation of electrowetting-on-dielectrics (EWOD). A reduction of the drain current is observed when the target droplet is merged with a pre-existing droplet on the embedded sensor. This reduction of the drain current is attributed to the specific binding of the antigen and the antibody of the AI. The proposed hybrid device consisting of the FET-based sensor and an EWOD device, built on a coplanar substrate by monolithic integration, is fully compatible with current fabrication technology for control and read-out circuitry. Such a completely electrical manner of inducing the transport of bio-molecules, the detection of bio-molecules, the recording of signals, signal processing, and the data transmission process does not require a pump, a fluidic channel, or a bulky transducer. Thus, the proposed platform can contribute to the construction of an all-in-one chip. C1 [Choi, Kyungyong; Kim, Jee-Yeon; Ahn, Jae-Hyuk; Choi, Ji-Min; Choi, Yang-Kyu] Korea Adv Inst Sci & Technol, Dept Elect Engn, Taejon 305701, South Korea. [Im, Maesoon] Harvard Univ, Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. RP Choi, YK (reprint author), Korea Adv Inst Sci & Technol, Dept Elect Engn, Taejon 305701, South Korea. EM ykchoi@ee.kaist.ac.kr FU National Research Foundation of Korea (NRF); Korean Ministry of Education, Science and Technology (MEST) [2011-0020487]; National Research and Development Program (NRDP) [2011-0002182] FX This research was supported by a grant from the National Research Foundation of Korea (NRF) funded by the Korean Ministry of Education, Science and Technology (MEST) (no. 2011-0020487). It was also partially supported by the National Research and Development Program (NRDP, 2011-0002182) for the development of biomedical function monitoring biosensors. NR 23 TC 23 Z9 23 U1 1 U2 54 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 1473-0197 J9 LAB CHIP JI Lab Chip PY 2012 VL 12 IS 8 BP 1533 EP 1539 DI 10.1039/c2lc21203j PG 7 WC Biochemical Research Methods; Chemistry, Multidisciplinary; Nanoscience & Nanotechnology SC Biochemistry & Molecular Biology; Chemistry; Science & Technology - Other Topics GA 914XL UT WOS:000301986500020 PM 22402581 ER PT S AU Kural, C Kirchhausen, T AF Kural, Comert Kirchhausen, Tom BE Conn, PM TI LIVE-CELL IMAGING OF CLATHRIN COATS SO METHODS IN ENZYMOLOGY, VOL 505: IMAGING AND SPECTROSCOPIC ANALYSIS OF LIVING CELLS: LIVE CELL IMAGING OF CELLULAR ELEMENTS AND FUNCTIONS SE Methods in Enzymology LA English DT Review; Book Chapter ID MEDIATED ENDOCYTOSIS; PLASMA-MEMBRANE; VESICLE COATS; IN-VIVO; PROTEINS; PITS; ACTIN; RECRUITMENT; DYNAMICS; ADAPTER AB We compare the use of two-dimensional total internal reflection fluorescence microscopy with a rapid, simple-to-implement method for three-dimensional (3D) imaging using spinning-disk confocal microscopy suitable for reliable 3D tracking of clathrin-coated endocytic and endosomal carriers. These carriers contain about 20 EGFP (enhanced green fluorescent protein) equivalents of a chimeric fluorescent protein (either clathrin light chain or one of the clathrin adaptor subunits). Under tissue culture conditions, the clathrin-containing carriers correspond to a variable number of relatively sparse, diffraction-limited, fluorescent objects that can be identified with a spatial precision of similar to 30 nm or better and a temporal resolution of <1 s. The applicability of these approaches to mammalian cells in culture allows investigators detailed monitoring of the composition dynamics of the clathrin-containing carriers which can then be used to study in living cells the molecular mechanisms required for the formation and traffic of clathrin-coated pits and vesicles. C1 [Kural, Comert; Kirchhausen, Tom] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. [Kural, Comert; Kirchhausen, Tom] Childrens Hosp, Immune Dis Inst, Boston, MA 02115 USA. [Kural, Comert; Kirchhausen, Tom] Childrens Hosp, Program Cellular & Mol Med, Boston, MA 02115 USA. RP Kural, C (reprint author), Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. FU NIAID NIH HHS [U54 AI057159]; NIGMS NIH HHS [R01 GM075252, GM 075252] NR 61 TC 5 Z9 5 U1 3 U2 17 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0076-6879 BN 978-0-12-388448-0 J9 METHOD ENZYMOL JI Methods Enzymol. PY 2012 VL 505 BP 59 EP 80 DI 10.1016/B978-0-12-388448-0.00012-7 PG 22 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BZG69 UT WOS:000301550700004 PM 22289448 ER PT B AU Munn, LL Kamoun, W Dupin, M Tyrrell, JA AF Munn, Lance L. Kamoun, Walid Dupin, Michael Tyrrell, James Alex BA Jackson, TL BF Jackson, TL TI Modeling Structural and Functional Adaptation of Tumor Vessel Networks During Antiangiogenic Therapy SO MODELING TUMOR VASCULATURE: MOLECULAR, CELLULAR, AND TISSUE LEVEL ASPECTS AND IMPLICATIONS LA English DT Article; Book Chapter ID ENDOTHELIAL GROWTH-FACTOR; LATTICE BOLTZMANN ANALYSIS; ANTI-ANGIOGENIC THERAPY; VASCULAR NORMALIZATION; BLOOD-FLOW; SKELETAL-MUSCLE; POSTCAPILLARY EXPANSIONS; MATHEMATICAL-MODEL; METABOLIC STIMULI; KINASE INHIBITOR C1 [Munn, Lance L.; Kamoun, Walid; Dupin, Michael; Tyrrell, James Alex] Massachusetts Gen Hosp, Charlestown, MA 02129 USA. [Munn, Lance L.; Kamoun, Walid; Dupin, Michael; Tyrrell, James Alex] Harvard Univ, Sch Med, Charlestown, MA 02129 USA. RP Munn, LL (reprint author), Massachusetts Gen Hosp, 149 13th St,Room 3409, Charlestown, MA 02129 USA. EM lance@steele.mgh.harvard.edu; walid@steele.mgh.harvard.edu; mdupin@steele.mgh.harvard.edu; james@steele.mgh.harvard.edu RI Munn, Lance/L-3950-2016 OI Munn, Lance/0000-0003-0698-7232 NR 85 TC 1 Z9 2 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 978-1-4614-0051-6 PY 2012 BP 213 EP 233 DI 10.1007/978-1-4614-0052-3_9 D2 10.1007/978-1-4614-0052-3 PG 21 WC Mathematical & Computational Biology; Pathology SC Mathematical & Computational Biology; Pathology GA BZJ07 UT WOS:000301749700009 ER PT S AU Greka, A Mundel, P AF Greka, Anna Mundel, Peter BE Julius, D Clapham, DE TI Cell Biology and Pathology of Podocytes SO ANNUAL REVIEW OF PHYSIOLOGY, VOL 74 SE Annual Review of Physiology LA English DT Review; Book Chapter DE glomerulus; foot process; slit diaphragm; actin cytoskeleton; calcium; angiotensin; synaptopodin; TRPC channels; Rac1; RhoA; integrins; mTOR; autophagy ID FOCAL SEGMENTAL GLOMERULOSCLEROSIS; INTEGRIN-LINKED KINASE; GLOMERULAR SLIT DIAPHRAGM; RESISTANT NEPHROTIC SYNDROME; PROTEINURIC KIDNEY-DISEASE; PARIETAL EPITHELIAL-CELLS; TUMOR SUPPRESSOR GENE; NAIL-PATELLA SYNDROME; ANGIOTENSIN-II; WILMS-TUMOR AB As an integral member of the filtration barrier in the kidney glomerulus, the podocyte is in a unique geographical position: It is exposed to chemical signals from the urinary space (Bowman's capsule), it receives and transmits chemical and mechanical signals to/from the glomerular basement membrane upon which it elaborates, and it receives chemical and mechanical signals from the vascular space with which it also communicates. As with every cell, the ability of the podocyte to receive signals from the surrounding environment and to translate them to the intracellular milieu is dependent largely on molecules residing on the cell membrane. These molecules are the first-line soldiers in the ongoing battle to sense the environment, to respond to friendly signals, and to defend against injurious foes. In this review, we take a membrane biologist's view of the podocyte, examining the many membrane receptors, channels, and other signaling molecules that have been implicated in podocyte biology. Although we attempt to be comprehensive, our goal is not to capture every membrane-mediated pathway but rather to emphasize that this approach may be fruitful in understanding the podocyte and its unique properties. C1 [Greka, Anna] Massachusetts Gen Hosp, Dept Med, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. RP Greka, A (reprint author), Massachusetts Gen Hosp, Dept Med, Charlestown, MA 02129 USA. EM greka.anna@mgh.harvard.edu; mundel.peter@mgh.harvard.edu FU NIDDK NIH HHS [R01 DK062472, DK062472, DK083511, DK57683, K08 DK083511, R01 DK057683, R01 DK091218] NR 198 TC 141 Z9 148 U1 7 U2 51 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0897 USA SN 0066-4278 BN 978-0-8243-0374-7 J9 ANNU REV PHYSIOL JI Annu. Rev. Physiol. PY 2012 VL 74 BP 299 EP 323 DI 10.1146/annurev-physiol-020911-153238 PG 25 WC Physiology SC Physiology GA BZJ96 UT WOS:000301794000014 PM 22054238 ER PT J AU Foley, JM Ettenhofer, ML Kim, MS Behdin, N Castellon, SA Hinkin, CH AF Foley, Jessica M. Ettenhofer, Mark L. Kim, Michelle S. Behdin, Nina Castellon, Steven A. Hinkin, Charles H. TI Cognitive Reserve as a Protective Factor in Older HIV-Positive Patients at Risk for Cognitive Decline SO APPLIED NEUROPSYCHOLOGY-ADULT LA English DT Article DE aging; cognitive reserve; HIV; neuropsychologically intact; protective factors ID INFECTED ADULTS; VIRUS-INFECTION; AIDS; EDUCATION; AGE; INDIVIDUALS; PERFORMANCE; HYPOTHESIS; DEMENTIA; DISEASE AB The present study examined the impact of cognitive reserve in maintaining intact neuropsychological (NP) function among older HIV-positive individuals, a uniquely at-risk subgroup. Participants included 129 individuals classified by HIV serostatus, age group, and NP impairment. A three-way analysis of variance (ANOVA) followed by a series of within-group ANOVA and multiple regression analyses were conducted to investigate the pattern of cognitive reserve (vs. other protective) influence among groups with varying risks of NP impairment. Results indicated a significant age x HIV status interaction, with older HIV-positive individuals demonstrating higher cognitive reserve than subgroups with less risk for NP compromise (younger age and/or HIV-negative). Results demonstrated higher cognitive reserve specific to NP-intact older HIV-positive individuals. Within this group, the interaction of younger age and higher cognitive reserve independently contributed to cognitive status when controlling for psychiatric, immunological, and psychosocial protective mechanisms, suggesting the importance of cognitive reserve beyond other protective mechanisms in maintaining optimal NP functioning in those individuals most at risk. Alongside younger age, factors contributing to cognitive reserve (i.e., education and estimated premorbid intelligence) may provide substantial benefit for older HIV-positive adults who are at high risk for NP compromise. C1 [Foley, Jessica M.] Harvard Univ, Sch Med, VA Boston Healthcare Syst, Dept Psychiat, Brockton, MA 02301 USA. [Foley, Jessica M.; Ettenhofer, Mark L.; Castellon, Steven A.; Hinkin, Charles H.] Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Semel Inst Neurosci & Human Behav, Los Angeles, CA 90024 USA. [Ettenhofer, Mark L.] Uniformed Serv Univ Hlth Sci, Dept Med & Clin Psychol, Bethesda, MD 20814 USA. [Kim, Michelle S.; Castellon, Steven A.; Hinkin, Charles H.] W Los Angeles Vet Affairs Med Ctr, Dept Psychiat, Los Angeles, CA 90073 USA. [Behdin, Nina] Univ Calif Los Angeles, Dept Psychol, Los Angeles, CA 90024 USA. RP Foley, JM (reprint author), Harvard Univ, Sch Med, VA Boston Healthcare Syst, Dept Psychiat, 940 Belmont St, Brockton, MA 02301 USA. EM jfoley@post.harvard.edu FU VA Merit Review: Aging & HIV/AIDS: Neurocognitive Sequelae and Functional Consequences; Neuropsychology of HIV/AIDS [5 T32 MH19535] FX This study was conducted at the University of California Los Angeles and the West Los Angeles Veteran's Affairs Medical Center and was supported by VA Merit Review: Aging & HIV/AIDS: Neurocognitive Sequelae and Functional Consequences to CHH, and 5 T32 MH19535: Neuropsychology of HIV/AIDS to CHH. NR 37 TC 16 Z9 16 U1 2 U2 3 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 0908-4282 EI 1532-4826 J9 APPL NEUROPSYCH-ADUL JI Appl. Neuropsychol.-Adult PY 2012 VL 19 IS 1 BP 16 EP 25 DI 10.1080/09084282.2011.595601 PG 10 WC Clinical Neurology; Psychology SC Neurosciences & Neurology; Psychology GA 909XZ UT WOS:000301602000004 PM 22385375 ER PT J AU Bloom, JD Bleier, BS Goldstein, SA Carniol, PJ Palmer, JN Cohen, NA AF Bloom, Jason D. Bleier, Benjamin S. Goldstein, Stephen A. Carniol, Paul J. Palmer, James N. Cohen, Noam A. TI Laser Facial Nerve Welding in a Rabbit Model SO ARCHIVES OF FACIAL PLASTIC SURGERY LA English DT Article ID IN-VIVO; ANIMAL-MODEL; REPAIR; SUTURE; RAT; REGENERATION; ANASTOMOSIS; SOLDER AB Objective: To assess the feasibility of laser tissue welding for repair of facial nerve injury. Methods: In a prospective in vivo animal survival surgery model, rabbit facial nerve injury was followed by either standard suture neurorrhaphy or laser tissue welding using a diode laser (808 +/- 1 nm) to weld biological solder. Rabbits were evaluated at 4, 8, 12, and 16 weeks by facial videography and electromyography. Histopathological analysis of the repair was performed at 4 and 16 weeks. Results: Videographic analysis demonstrated the laser tissue welding repair trended toward superior outcomes compared with suture neurorrhaphy at all 4 time points. Electrophysiological analysis demonstrated similar or better results, with statistically significant improvement at week 16 (P < .05). Histologic analysis demonstrated no difference in axon organization or extravasation between groups; however, the laser nerve repair created a greater initial inflammatory reaction. An analysis of operative time demonstrated significantly decreased time and ease of use for laser tissue welding. Conclusions: This pilot study demonstrates that laser nerve welding may be an expedient, feasible, and safe method for facial nerve repair in a rabbit model. Further experiments with larger numbers are needed to provide additional evidence that laser tissue welding produces a neurorrhaphy that has functional, electrophysiological, and histological results that could rival traditional suture neurorrhaphy. Arch Facial Plast Surg. 2012;14(1):52-58. Published online August 15, 2011. doi: 10.1001/archfacial.2011.61 C1 [Bloom, Jason D.] NYU, Dept Otolaryngol, Langone Med Ctr, Div Facial Plast & Reconstruct Surg, New York, NY 10016 USA. [Bleier, Benjamin S.] Harvard Univ, Sch Med, Dept Otolaryngol Head & Neck Surg, Boston, MA USA. [Bleier, Benjamin S.] Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. [Goldstein, Stephen A.] Univ Arizona, Dept Surg, Div Otolaryngol, Tucson, AZ USA. [Goldstein, Stephen A.] Univ Arizona, Dept Surg, Div Facial Plast & Reconstruct Surg, Tucson, AZ USA. [Carniol, Paul J.] Carniol Res Ctr, Summit, NJ USA. [Palmer, James N.; Cohen, Noam A.] Univ Penn, Dept Otorhinolaryngol Head & Neck Surg, Philadelphia, PA 19104 USA. RP Bloom, JD (reprint author), NYU, Dept Otolaryngol, Langone Med Ctr, Div Facial Plast & Reconstruct Surg, 550 1st Ave,NBV Ste 5E5, New York, NY 10016 USA. EM bloomj@gmail.com OI Cohen, Noam/0000-0002-9462-3932 FU American Academy of Otolaryngology-Head and Neck Surgery Resident Research Centralized Otolaryngology Research Efforts (CORE) FX This research project is the recipient of the 2009 American Academy of Otolaryngology-Head and Neck Surgery Resident Research Centralized Otolaryngology Research Efforts (CORE) Grant ($5000). NR 20 TC 4 Z9 4 U1 0 U2 4 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 1521-2491 J9 ARCH FACIAL PLAST S JI Arch. Facial Plast. Surg. PD JAN-FEB PY 2012 VL 14 IS 1 BP 52 EP 58 DI 10.1001/archfacial.2011.61 PG 7 WC Surgery SC Surgery GA 912YF UT WOS:000301836800010 PM 21844481 ER PT J AU Stewart, S O'Riley, A Edelstein, B Gould, C AF Stewart, Sarah O'Riley, Alisa Edelstein, Barry Gould, Christine TI A Preliminary Comparison of Three Cognitive Screening Instruments in Long Term Care: The MMSE, SLUMS, and MoCA SO CLINICAL GERONTOLOGIST LA English DT Article DE assessment; cognitive screening; dementia; memory ID MINI-MENTAL-STATE; PARKINSONS-DISEASE; ALZHEIMERS-DISEASE; EDUCATIONAL-LEVEL; DEMENTIA; IMPAIRMENT; VALIDITY; RELIABILITY; POPULATION; VALIDATION AB The Mini-Mental State Examination (MMSE) is a widely utilized cognitive screening instrument. Despite its popularity, there are problems with this instrument. Many researchers have questioned the utility of the MMSE when used among adults without cognitive impairment. Additionally, the MMSE lacks tasks targeting a wider variety of cognitive domains. Finally, the MMSE is no longer in the public domain and may be too costly for some settings. Given these problems, some mental health settings may be obliged to utilize another instrument, such as the Montreal Cognitive Assessment (MoCA) or the Saint Louis Mental Status Examination (SLUMS). The present pilot study examined the current literature related to the MoCA, SLUMS, and MMSE and compared performances on these measures across a sample of participants. A within-subject design was utilized to compare performance on the MMSE, MoCA, and SLUMS in a sample of 40 long-term care residents (aged 48-89). Several participants appeared to lack clinically significant cognitive deficits as assessed by the MMSE, but demonstrated clinically significant deficits as assessed by the MoCA or SLUMS. The MMSE was significantly positively correlated with both the MoCA (r = .90) and the SLUMS (r = .83). The results of this pilot study have important implications regarding how to choose an appropriate replacement for the MMSE for practitioners who utilize cognitive screening instruments. C1 [Stewart, Sarah] S Texas Vet Healthcare Syst, San Antonio, TX 78229 USA. [O'Riley, Alisa] Univ Rochester, Med Ctr, Rochester, NY 14642 USA. [Edelstein, Barry; Gould, Christine] W Virginia Univ, Morgantown, WV 26506 USA. RP Stewart, S (reprint author), S Texas Vet Healthcare Syst, 7400 Merton Minter Blvd, San Antonio, TX 78229 USA. EM Sarah.Stoner@va.gov NR 50 TC 6 Z9 6 U1 1 U2 8 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 0731-7115 J9 CLIN GERONTOLOGIST JI Clin. Gerontol. PY 2012 VL 35 IS 1 BP 57 EP 75 DI 10.1080/07317115.2011.626515 PG 19 WC Geriatrics & Gerontology; Gerontology; Psychiatry SC Geriatrics & Gerontology; Psychiatry GA 911RZ UT WOS:000301738600005 ER PT J AU Bland, SE Mimiaga, MJ Reisner, SL White, JM Driscoll, MA Isenberg, D Cranston, K Mayer, KH AF Bland, Sean E. Mimiaga, Matthew J. Reisner, Sari L. White, Jaclyn M. Driscoll, Maura A. Isenberg, Deborah Cranston, Kevin Mayer, Kenneth H. TI Sentencing risk: history of incarceration and HIV/STD transmission risk behaviours among Black men who have sex with men in Massachusetts SO CULTURE HEALTH & SEXUALITY LA English DT Article DE Black; men who have sex with men; incarceration; HIV; STDs; USA ID AFRICAN-AMERICAN MEN; SEXUALLY-TRANSMITTED INFECTIONS; HIV-INFECTION; HIDDEN POPULATIONS; DISPARITIES; PREVENTION; COMMUNITY; HIV/AIDS; STRESS AB This study investigated the role of incarceration in HIV/STD risk among 197 Black men who have sex with men in Massachusetts, USA. More than half (51%) reported a history of incarceration (28% <90 days in jail/prison; 23% >= 90 days in jail/prison). Multivariable logistic regression models adjusted for age and sexual orientation examined associations between demographic, behavioural, social-psychological and cultural factors and incarceration history. Factors associated with,90 days of incarceration were: unprotected sex with a man, STD history, injection drug use and substance abuse treatment. Factors associated with >= 90 days of incarceration were: unprotected sex with a woman, crack use during sex, STD history, injection drug use, substance abuse treatment, depressive symptoms, post-traumatic stress symptoms, HIV fatalism and social capital. Black men who have sex with men with incarceration histories may be at increased risk for HIV/STDs compared to those without such histories. HIV prevention efforts that focus on individual risk and cultural-contextual issues among Black men who have sex with men are warranted. C1 [Bland, Sean E.; Mimiaga, Matthew J.; Reisner, Sari L.; White, Jaclyn M.; Mayer, Kenneth H.] Fenway Hlth, Fenway Inst, Boston, MA 02215 USA. [Mimiaga, Matthew J.; Reisner, Sari L.] Harvard Univ, Sch Publ Hlth, Dept Soc Human Dev & Hlth, Boston, MA 02115 USA. [Mimiaga, Matthew J.; Reisner, Sari L.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Mimiaga, Matthew J.; Mayer, Kenneth H.] Harvard Univ, Sch Med, Boston, MA USA. [Mimiaga, Matthew J.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Driscoll, Maura A.; Isenberg, Deborah; Cranston, Kevin] Massachusetts Dept Publ Hlth, Boston, MA USA. [Mayer, Kenneth H.] Beth Israel Deaconess Med Ctr, Div Infect Dis, Boston, MA 02215 USA. RP Mimiaga, MJ (reprint author), Fenway Hlth, Fenway Inst, Boston, MA 02215 USA. EM mmimiaga@fenwayhealth.org NR 41 TC 12 Z9 12 U1 12 U2 17 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 1369-1058 J9 CULT HEALTH SEX JI Cult. Health Sex PY 2012 VL 14 IS 3 BP 329 EP 345 DI 10.1080/13691058.2011.639902 PG 17 WC Family Studies; Social Sciences, Biomedical SC Family Studies; Biomedical Social Sciences GA 911IN UT WOS:000301710600007 PM 22150578 ER PT S AU Srinivasan, C Peer, D Shimaoka, M AF Srinivasan, Charudharshini Peer, Dan Shimaoka, Motomu BE Ley, MD TI Integrin-Targeted Stabilized Nanoparticles for an Efficient Delivery of siRNAs In Vitro and In Vivo SO CYTOKINE PROTOCOLS SE Methods in Molecular Biology LA English DT Article; Book Chapter DE Liposomes; RNAi; Leukocytes; Inflammation; Hyaluronan; Antibody; Transfection; Systemic delivery ID SMALL INTERFERING RNA; NONVIRAL DELIVERY; GENE; EXPRESSION; LYMPHOCYTES; MICE AB Utilizing small interfering RNAs (siRNAs) to silence disease-associated genes holds promise as a potential therapeutic strategy. However, the greatest challenge for RNAi remains the delivery of siRNA to target tissues or cells. Specifically lymphocytes are difficult to transduce by conventional methods but represent good targets for anti-inflammatory therapeutics. Integrins are an important class of cell adhesion receptors on leukocytes. Antibodies to integrins have been used to inhibit inflammatory reactions in patients. Here, we describe a strategy to deliver the siRNA cargo to leukocytes by stabilized nanoparticles surface-decorated with antibodies to integrin as targeting moieties. A detailed methodology for preparation of the integrin-targeted stabilized nanoparticles (I-tsNPs) and their delivery in vitro and in vivo is discussed. C1 [Srinivasan, Charudharshini; Shimaoka, Motomu] Immune Dis Inst, Boston, MA USA. [Srinivasan, Charudharshini; Shimaoka, Motomu] Childrens Hosp, Program Cellular & Mol Med, Boston, MA 02115 USA. [Srinivasan, Charudharshini; Shimaoka, Motomu] Harvard Univ, Sch Med, Dept Anesthesia, Boston, MA 02115 USA. [Peer, Dan] Tel Aviv Univ, George S Wise Fac Life Sci, Lab Nanomed, Dept Cell Res & Immunol, IL-69978 Tel Aviv, Israel. [Peer, Dan] Tel Aviv Univ, Ctr Nanosci & Nanotechnol, IL-69978 Tel Aviv, Israel. RP Srinivasan, C (reprint author), Immune Dis Inst, Boston, MA USA. RI Peer, Dan/A-1785-2011 OI Peer, Dan/0000-0001-8238-0673 NR 22 TC 4 Z9 4 U1 0 U2 8 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-61779-438-4 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2012 VL 820 BP 105 EP 116 DI 10.1007/978-1-61779-439-1_7 D2 10.1007/978-1-61779-439-1 PG 12 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BYN05 UT WOS:000299396700007 PM 22131028 ER PT J AU Teerlink, JR Iragui, VJ Mohr, JP Carson, PE Hauptman, PJ Lovett, DH Miller, AB Pina, IL Thomson, S Varosy, PD Zile, MR Cleland, JGF Givertz, MM Metra, M Ponikowski, P Voors, AA Davison, BA Cotter, G Wolko, D DeLucca, P Salerno, CM Mansoor, GA Dittrich, H O'Connor, CM Massi, BM AF Teerlink, John R. Iragui, Vicente J. Mohr, Jay P. Carson, Peter E. Hauptman, Paul J. Lovett, David H. Miller, Alan B. Pina, Ileana L. Thomson, Scott Varosy, Paul D. Zile, Michael R. Cleland, John G. F. Givertz, Michael M. Metra, Marco Ponikowski, Piotr Voors, Adriaan A. Davison, Beth A. Cotter, Gad Wolko, Denise DeLucca, Paul Salerno, Christina M. Mansoor, George A. Dittrich, Howard O'Connor, Christopher M. Massi, Barry M. TI The Safety of an Adenosine A(1)-Receptor Antagonist, Rolofylline, in Patients with Acute Heart Failure and Renal Impairment Findings from PROTECT SO DRUG SAFETY LA English DT Article ID RANDOMIZED CONTROLLED-TRIAL; A(1) RECEPTOR ANTAGONIST; ACUTE ISCHEMIC-STROKE; KW-3902 AB Background: Adenosine exerts actions in multiple organ systems, and adenosine receptors are a therapeutic target in many development programmes. Objective: The aim of this analysis was to evaluate the safety of rolofylline, an adenosine A(1)-receptor antagonist, in patients with acute heart failure. Methods: The effect of rolofylline was investigated in patients hospitalized for acute heart failure with impaired renal function. Intravenous rolofylline 30 mg or placebo was infused over 4 hours daily for up to 3 days. Adverse events (AEs) and serious AEs (SAEs) were recorded from baseline through 7 and 14 days, respectively, and clinical events were adjudicated through 60 days. Results: Of 2033 patients enrolled, 2002 received study drug randomized 2: 1 to rolofylline or placebo. Rolofylline and placebo were associated with a similar risk of pre-specified groups of AEs or SAEs, other than selected neurological events. Investigator-reported seizures occurred in 11(0.8%) rolofylline-treated patients and zero patients receiving placebo (p = 0.02). Stroke occurred in 21(1.6%) patients assigned to rolofylline compared with 3 (0.5%) placebo-treated patients through 60 days with a greater risk for stroke in the rolofylline group (hazard ratio 3.49; 95% CI 1.04, 11.71; p = 0.043). There was no temporal relation to rolofylline administration and no specific stroke subtype or clinical characteristics that predicted stroke in the rolofylline group. Conclusions: Rolofylline treatment was associated with an increased seizure rate, an anticipated complication of A(1)-receptor antagonists. An unanticipated, disproportionate increase in strokes in the rolofylline-treated patients emerged, although no clear temporal relation, aetiology, stroke subtype or interacting factor suggestive of a causal mechanism was identified. Further research into stroke as a potential complication of adenosine-modulating therapies is required. Additionally, this study underscores the value of longer follow-up durations for AEs, even for agents with short treatment periods, such as in acute heart failure. C1 [Teerlink, John R.] San Francisco VA Med Ctr, Cardiol Sect, San Francisco, CA 94121 USA. [Teerlink, John R.; Lovett, David H.; Massi, Barry M.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Iragui, Vicente J.] Univ Calif San Diego, San Diego, CA 92103 USA. [Carson, Peter E.] Washington DC Vet Affairs Med Ctr, Washington, DC USA. [Carson, Peter E.] Georgetown Univ, Washington, DC USA. [Hauptman, Paul J.] St Louis Univ, Sch Med, St Louis, MO USA. [Miller, Alan B.] Univ Florida, Hlth Sci Ctr, Jacksonville, FL 32209 USA. [Pina, Ileana L.] Cleveland Vet Affairs Med Ctr, Cleveland, OH USA. [Pina, Ileana L.] Case Western Reserve Univ, Cleveland, OH 44106 USA. [Thomson, Scott] Univ Calif San Diego, San Diego Vet Affairs Med Ctr, San Diego, CA 92103 USA. [Varosy, Paul D.] Vet Affairs Eastern Colorado Hlth Care Syst, Denver, CO USA. [Varosy, Paul D.] Univ Colorado, Denver, CO 80202 USA. [Zile, Michael R.] RHJ Dept Vet Affairs Med Ctr, Charleston, SC USA. [Zile, Michael R.] Med Univ S Carolina, Charleston, SC 29425 USA. [Cleland, John G. F.] Univ Hull, Kingston Upon Hull, Yorks, England. [Givertz, Michael M.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Metra, Marco] Univ Brescia, Brescia, Italy. [Ponikowski, Piotr] Med Univ, Clin Mil Hosp, Wroclaw, Poland. [Voors, Adriaan A.] Univ Groningen, Univ Med Ctr Groningen, NL-9713 AV Groningen, Netherlands. [Davison, Beth A.; Cotter, Gad] Momentum Res Inc, Durham, NC USA. [Wolko, Denise; DeLucca, Paul; Salerno, Christina M.] Merck Res Labs, N Wales, PA USA. [Mansoor, George A.] Merck Res Labs, Rahway, NJ USA. [Dittrich, Howard] NovaCardia Inc, San Diego, CA USA. [O'Connor, Christopher M.] Duke Univ, Med Ctr, Durham, NC USA. [Mohr, Jay P.] Columbia Univ, Coll Phys & Surg, New York, NY USA. RP Teerlink, JR (reprint author), San Francisco VA Med Ctr, Cardiol Sect, 111C,4150 Clement St, San Francisco, CA 94121 USA. EM john.teerlink@ucsf.edu RI Teerlink, John/D-2986-2012; Ponikowski, Piotr/O-6454-2015; OI Ponikowski, Piotr/0000-0002-3391-7064; Davison, Beth/0000-0003-2374-6449; Cleland, John/0000-0002-1471-7016; Metra, Marco/0000-0001-6691-8568 FU NovaCardia, a subsidiary of Merck FX Funding for this study was provided by NovaCardia, a subsidiary of Merck. Representatives of the sponsor were directly involved in the design and conduct of the study; collection, management, analysis and interpretation of the data; and preparation, review and approval of the manuscript.; The authors declare the following conflicts of interest in relation to the content of this study: Peter E. Carson received honorarium for services on the Clinical Events Committee; John G.F. Cleland received fees for work as a PROTECT steering committee member, and consulted with Merck on an international advisory board. He has also received support for travel and speakers' bureaus; Gad Cotter has received consulting fee/honorarium and is an employee of Momentum Research Inc., who provided consulting services to NovaCardia; Beth Davison received consulting fee/honorarium and is an employee of Momentum Research Inc., who provided consulting services to NovaCardia; Paul De Lucca is an employee of Merck and has received stock options as part of his employee compensation, and has received travel payments; Howard Dittrich received consulting fee/honorarium and support for travel, and is an employee of NovaCardia (acquired by Merck in 2007). He is also a consultant to Merck, with stock ownership of NovaCardia and Merck, and had a patent issued (no money was received); Michael M. Givertz received institutional research support for participation in the PROTECT study, and has served as a Scientific Advisory Baord member for Merck; Paul J. Hauptman was a member of the Clinical Events Committee and a site co-principal investigator on the PROTECT study. He received funding from NovaCardia and Merck; Vicente lragui served as a consultant, and received honoraria for conduct of the research but not for preparation of the manuscript; David H. Lovett received payments for the PROTECT Clinical Events Committee from Merck/NovaCardia, and has received payments for work as a member of Merck's speakers' bureau; George A. Mansoor is an employee of Merck, owns stock options in Merck and has received travel payments; Barry M. Massie received compensation for consultation from the sponsor, Merck/NovaCardia, for time spent on the design and oversight of this trial in his capacity of co-principal investigator and has received support for travel; Marco Metra has received honoraria for participation in advisory boards and speeches from Bayer, Corthera, Merck, Novartis and Servier, in addition to support for travel; Alan D. Miller received payments for work as a member of the Clinical Events Committee of the PROTECT study; J.P. Mohr received payments for the PROTECT Clinical Events Committee from Merck/NovaCardia; Christopher O'Connor received research funding from NovaCardia/Merck; Ileana Pina was a member of the Clinical Endpoints Committee that adjudicated events in the trial and received honoraria for the time involved in the adjudication work. Members were blinded during the entire process; Piotr Ponikowski received payments from NovaCardia/Merck for work performed on the PROTECT study and received honoraria from Merck as a speaker; Christina Salerno is an employee of Merck and discloses ownership of stock options and receipt of travel payments; John Teerlink received payments for clinical research for services as the Chairperson on the Clinical Events Committee for the PROTECT study; Scott Thomson occasionally consults for Merck and has previously consulted to NovaCardia; Paul D. Varosy was a member of the blinded, independent Clinical Endpoints Committee for the PROTECT study. In this capacity, he adjudicated clinical endpoints but was blinded to the patients' randomization status. All processes were conducted in compliance with FDA-mandated Good Clinical Practice. He received compensation for this work from Merck, which funded the study.; Last funding was received in July 2009; Adriaan Voors received payments for work performed on the PROTECT study from NovaCardia/Merck. In addition, Dr Voors received speakers' fees and advisory board payments from NovaCardia/Merck; Denise Wolko is an employee of Merck, owns stock or stock options in the company and has received travel payments; Michael R. Zile served as a member of the Events Committee of the PROTECT study and received an honorarium to perform this task. NR 26 TC 18 Z9 18 U1 1 U2 2 PU ADIS INT LTD PI AUCKLAND PA 41 CENTORIAN DR, PRIVATE BAG 65901, MAIRANGI BAY, AUCKLAND 1311, NEW ZEALAND SN 0114-5916 J9 DRUG SAFETY JI Drug Saf. PY 2012 VL 35 IS 3 BP 233 EP 244 PG 12 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy; Toxicology SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy; Toxicology GA 910DT UT WOS:000301618100005 PM 22339573 ER PT S AU Tse, WKF Jiang, YJ AF Tse, William Ka Fai Jiang, Yun-Jin BE Kaufmann, M Klinger, C TI Functional Screen of Zebrafish Deubiquitylating Enzymes by Morpholino Knockdown and In Situ Hybridization SO FUNCTIONAL GENOMICS: METHODS AND PROTOCOLS, SECOND EDITION SE Methods in Molecular Biology LA English DT Article; Book Chapter DE Deubiquitylating enzymes; In situ hybridization; "Loss-of-function" screening; Morpholino; Zebrafish ID DEUBIQUITINATING ENZYMES; UBIQUITIN AB In order to unfold the function of genes, solely performing mRNA over-expression is not enough nowadays. Traditional protein expression experiments, such as Western blotting and immunohistochemical staining, could only provide researchers the changes of expression levels and/or location of their targets. To make a more strong and convincing statement about gene function, it is necessary to perform both "gain-of-function" and "loss-of-function" studies. Both assays can be performed easily by transfccting DNA plasmid and siRNA in cell culture system; while in zebrafish, mRNA and morpholino (MO) microinjection can serve similar purposes. It is common for the zebrafish community to carry out microinjection experiments to explore a gene function. Instead of making a single knockdown/over-expression of a gene, we foresee that more and more large-scale screens on certain protein families will be performed in the future. Here, based on our previous experience in zebrafish "loss-of-function" screening on deubiquitylating enzymes, we describe a general work flow, from morpholino designation, in situ hybridization, to data analysis, as a reference for researchers who may be interested in a similar screen. C1 [Tse, William Ka Fai] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Craniofacial Dev Biol Lab,Ctr Regenerat Med, Boston, MA 02114 USA. [Jiang, Yun-Jin] Natl Hlth Res Inst, Inst Mol & Genom Med, Zhunan Town 35053, Miaoli County, Taiwan. RP Tse, WKF (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Craniofacial Dev Biol Lab,Ctr Regenerat Med, 185 Cambridge St, Boston, MA 02114 USA. RI Jiang, Yun-Jin/E-3995-2010; TSE, KA FAI WILLIAM/C-9384-2012 OI Jiang, Yun-Jin/0000-0003-0499-7306; TSE, KA FAI WILLIAM/0000-0002-3738-0460 NR 7 TC 6 Z9 6 U1 0 U2 3 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-61779-423-0 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2012 VL 815 BP 321 EP 331 DI 10.1007/978-1-61779-424-7_24 D2 10.1007/978-1-61779-424-7 PG 11 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BYN04 UT WOS:000299396500024 PM 22131002 ER PT S AU Trachtenberg, AJ Robert, JH Abdalla, AE Fraser, A He, SY Lacy, JN Rivas-Morello, C Truong, A Hardiman, G Ohno-Machado, L Liu, F Hovig, E Kuo, WP AF Trachtenberg, Alexander J. Robert, Jae-Hyung Abdalla, Azza E. Fraser, Andrew He, Steven Y. Lacy, Jessica N. Rivas-Morello, Chiara Truong, Allison Hardiman, Gary Ohno-Machado, Lucila Liu, Fang Hovig, Eivind Kuo, Winston Patrick BE Wang, J Tan, AC Tian, T TI A Primer on the Current State of Microarray Technologies SO NEXT GENERATION MICROARRAY BIOINFORMATICS: METHODS AND PROTOCOLS SE Methods in Molecular Biology LA English DT Editorial Material; Book Chapter DE Microarrays; Gene expression; One dye; Two dye; High throughput; QRT-PCR; Cross platform ID GENE-EXPRESSION MEASUREMENTS; SINGLE-NUCLEOTIDE POLYMORPHISM; CANCER; INFORMATION; AFFYMETRIX; PLATFORMS; ARRAYS; CDNA; REPRODUCIBILITY; BIOINFORMATICS AB DNA microarray technology has been used for genome-wide gene expression studies that incorporate molecular genetics and computer science analyses on massive levels. The availability of microarrays permit the simultaneous analysis of tens of thousands of genes for the purposes of gene discovery, disease diagnosis, improved drug development, and therapeutics tailored to specific disease processes. In this chapter, we provide an overview on the current state of common microarray technologies and platforms. Since many genes contribute to normal functioning, research efforts are moving from the search for a disease-specific gene to the understanding of the biochemical and molecular functioning of a variety of genes whose disrupted interaction in complicated networks can lead to a disease state. The field of microarrays has evolved over the past decade and is now standardized with a high level of quality control, while providing a relatively inexpensive and reliable alternative to studying various aspects of gene expression. C1 [Trachtenberg, Alexander J.; Lacy, Jessica N.; Rivas-Morello, Chiara; Kuo, Winston Patrick] Harvard Univ, Sch Med, Harvard Catalyst Lab Innovat Translat Technol, Boston, MA USA. [Truong, Allison] Univ Calif Los Angeles, Dept Biol, Los Angeles, CA 90024 USA. [Liu, Fang; Hovig, Eivind] Norwegian Radium Hosp, Inst Canc Res, Dept Tumor Biol, Oslo, Norway. [Liu, Fang] PubGene AS, Oslo, Norway. [Ohno-Machado, Lucila] Univ Calif San Diego, Div Biomed Informat, San Diego, CA 92103 USA. [Robert, Jae-Hyung; Kuo, Winston Patrick] Harvard Univ, Sch Dent Med, Dept Dev Biol, Boston, MA 02115 USA. [Abdalla, Azza E.] Univ S Carolina, Dept Biol, Columbia, SC 29208 USA. [Fraser, Andrew; Hardiman, Gary] BIDMC, Dept Allergy & Inflammat, Boston, MA USA. [He, Steven Y.] Univ Calif San Diego, Dept Med, San Diego, CA 92103 USA. [Hovig, Eivind] Norwegian Radium Hosp, Inst Canc Res, Dept Med Informat, Oslo, Norway. RP Trachtenberg, AJ (reprint author), Harvard Univ, Sch Med, Harvard Catalyst Lab Innovat Translat Technol, Boston, MA USA. RI Hovig, Eivind/H-2474-2011; OI Hovig, Eivind/0000-0002-9103-1077; Truong, Allison/0000-0002-9985-1280; Ohno-Machado, Lucila/0000-0002-8005-7327 FU NCRR NIH HHS [UL1 RR 025758, UL1 RR025758] NR 41 TC 6 Z9 6 U1 1 U2 3 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-61779-399-8 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2012 VL 802 BP 3 EP 17 DI 10.1007/978-1-61779-400-1_1 D2 10.1007/978-1-61779-400-1 PG 15 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Mathematical & Computational Biology GA BYQ68 UT WOS:000299796400001 PM 22130870 ER PT J AU King, D Ogilvie, M Michailidou, M Velmahos, G Alam, H deMoya, M Fikry, K AF King, D. Ogilvie, M. Michailidou, M. Velmahos, G. Alam, H. deMoya, M. Fikry, K. TI FIFTY-FOUR EMERGENT CRICOTHYROIDOTOMIES: ARE SURGEONS RELUCTANT TEACHERS? SO SCANDINAVIAN JOURNAL OF SURGERY LA English DT Review DE Cricothyroidotomy; surgical airway; tracheostomy; emergency medicine; trauma surgery ID DIFFICULT AIRWAY; MANAGEMENT AB Background: Emergent cricothyroidotomy remains an uncommon, but life-saving, core procedural training requirement for emergency medicine (EM) physician training. We hypothesized that, although most cricothyroidotomies occur in the emergency department (ED), they are rarely performed by EM physicians. Methods: We conducted a retrospective analysis of all emergent cricothyroidotomies performed at two large level one trauma centers over 10 years. Operators and assistants for all procedures were identified, as well as mechanism of injury and patient demographics were examined. Results: Fifty-four cricothyroidotomies were performed. Patients were: mean age of 50, 80% male and 90% blunt trauma. The most common primary operator was a surgeon (n = 47, 87%), followed by an Emergency Medical Services (EMS) provider (n = 6, 11%) and a EM physician (n = 1, 2%). In all cases, except those performed by EMS, the operator or assistant was an attending surgeon. All EMS procedures resulted in serious complications compared to in-hospital procedures (p < 0.0001). Conclusions: 1. Pre-hospital cricothyroidotomy results in serious complications. 2. Despite the ubiquitous presence of emergency medicine physicians in the ED, all cricothyroidotomies were performed by a surgeon, which may represent a serious emergency medicine training deficiency. C1 [King, D.] Massachusetts Gen Hosp, Div Trauma Emergency Surg & Surg Crit Care, Boston, MA 02141 USA. [King, D.; Michailidou, M.; Velmahos, G.; Alam, H.; deMoya, M.; Fikry, K.] Harvard Univ, Sch Med, Div Trauma Emergency Surg & Surg Crit Care, Boston, MA 02141 USA. [Ogilvie, M.] Univ Miami, Jackson Mem Hosp, Sch Med, Ryder Trauma Ctr,Div Trauma Surg, Miami, FL 33136 USA. RP King, D (reprint author), Massachusetts Gen Hosp, Div Trauma Emergency Surg & Surg Crit Care, 165 Cambridge St,Suite 810, Boston, MA 02141 USA. EM dking3@partners.org NR 5 TC 4 Z9 5 U1 0 U2 0 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1457-4969 EI 1799-7267 J9 SCAND J SURG JI Scand. J. Surg. PY 2012 VL 101 IS 1 BP 13 EP 15 PG 3 WC Surgery SC Surgery GA 912VY UT WOS:000301830700003 PM 22414462 ER PT B AU Feener, EP AF Feener, Edward P. BE TombranTink, J Barnstable, CJ Gardner, TW TI Proteomics in the Vitreous of Diabetic Retinopathy Patients SO VISUAL DYSFUNCTION IN DIABETES: THE SCIENCE OF PATIENT IMPAIRMENT AND HEALTH CARE SE Ophthalmology Research LA English DT Article; Book Chapter DE Diabetic retinopathy; Mass spectrometry; Proteomics; Retina; Vitreous ID ENDOTHELIAL GROWTH-FACTOR; SPECTROMETRY-BASED PROTEOMICS; MASS-SPECTROMETRY; MACULAR EDEMA; VITREORETINAL DISEASES; VASCULAR-PERMEABILITY; GEL-ELECTROPHORESIS; INTRAOCULAR FLUIDS; SOLUBLE-PROTEINS; CELL-GROWTH C1 Joslin Diabet Ctr, Boston, MA 02215 USA. RP Feener, EP (reprint author), Joslin Diabet Ctr, Boston, MA 02215 USA. NR 52 TC 0 Z9 0 U1 1 U2 3 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA BN 978-1-60761-149-3 J9 OPHTHALMOL RES JI Ophthalmol. Res. PY 2012 BP 173 EP 188 DI 10.1007/978-1-60761-150-9_11 D2 10.1007/978-1-60761-150-9 PG 16 WC Primary Health Care; Ophthalmology SC General & Internal Medicine; Ophthalmology GA BYQ71 UT WOS:000299796700012 ER PT J AU Wang, TY Mancuso, JJ Kazmi, SMS Dwelle, J Sapozhnikova, V Willsey, B Ma, LL Qiu, JZ Li, XK Dunn, AK Johnston, KP Feldman, MD Milner, TE AF Wang, Tianyi Mancuso, J. Jacob Kazmi, S. M. Shams Dwelle, Jordan Sapozhnikova, Veronika Willsey, Brian Ma, Li L. Qiu, Jinze Li, Xiankai Dunn, Andrew K. Johnston, Keith P. Feldman, Marc D. Milner, Thomas E. TI Combined two-photon luminescence microscopy and OCT for macrophage detection in the hypercholesterolemic rabbit aorta using plasmonic gold nanorose SO LASERS IN SURGERY AND MEDICINE LA English DT Article DE atherosclerosis; macrophage; nanorose; two-photon luminescence microscopy; optical coherence tomography; photothermal wave imaging ID OPTICAL COHERENCE TOMOGRAPHY; CORONARY-ARTERY-DISEASE; ATHEROSCLEROTIC PLAQUE STABILITY; CENTRAL-NERVOUS-SYSTEM; MYOCARDIAL-INFARCTION; IRON-OXIDE; IN-VIVO; MAGNETIC-RESONANCE; NANOPARTICLE; INFLAMMATION AB Background and Objectives The macrophage is an important early cellular marker related to risk of future rupture of atherosclerotic plaques. Two-channel two-photon luminescence (TPL) microscopy combined with optical coherence tomography (OCT) was used to detect, and further characterize the distribution of aorta-based macrophages using plasmonic gold nanorose as an imaging contrast agent. Study Design/Materials and Methods: Nanorose uptake by macrophages was identified by TPL microscopy in macrophage cell culture. Ex vivo aorta segments (8 x 8 x 2 mm(3)) rich in macrophages from a rabbit model of aorta inflammation were imaged by TPL microscopy in combination with OCT. Aorta histological sections (5 mm in thickness) were also imaged by TPL microscopy. Results: Merged two-channel TPL images showed the lateral and depth distribution of nanorose-loaded macrophages (confirmed by RAM-11 stain) and other aorta components (e.g., elastin fiber and lipid droplet), suggesting that nanorose-loaded macrophages are diffusively distributed and mostly detected superficially within 20 mm from the luminal surface of the aorta. Moreover, OCT images depicted detailed surface structure of the diseased aorta. Conclusions: Results suggest that TPL microscopy combined with OCT can simultaneously reveal macrophage distribution with respect to aorta surface structure, which has the potential to detect vulnerable plaques and monitor plaque-based macrophages overtime during cardiovascular interventions. Lasers Surg. Med. 44:49-59, 2012. (C) 2012 Wiley Periodicals, Inc. C1 [Wang, Tianyi; Kazmi, S. M. Shams; Dwelle, Jordan; Qiu, Jinze; Dunn, Andrew K.; Milner, Thomas E.] Univ Texas Austin, Dept Biomed Engn, Austin, TX 78712 USA. [Mancuso, J. Jacob; Sapozhnikova, Veronika; Li, Xiankai; Feldman, Marc D.] Univ Texas Hlth Sci Ctr San Antonio, Div Cardiol, San Antonio, TX 78229 USA. [Willsey, Brian; Ma, Li L.; Johnston, Keith P.] Univ Texas Austin, Dept Chem Engn, Austin, TX 78712 USA. [Feldman, Marc D.] S Texas Vet Hlth Care Syst, San Antonio, TX 78229 USA. RP Milner, TE (reprint author), Univ Texas Austin, Dept Biomed Engn, 1 Univ Stn,C0800, Austin, TX 78712 USA. EM terra.laser@gmail.com RI Dunn, Andrew/I-9527-2014; OI Ma, Li/0000-0002-0959-5616 FU American Society for Laser Medicine and Surgery; Veterans Administration; Welch Foundation [F-1319]; NSF [CBET-0968038]; Department of Energy Center for Frontiers of Subsurface Energy Security FX The authors would like to acknowledge the technical support from the University of Texas Health Science Center at San Antonio. This study was supported in part by a travel grant from the American Society for Laser Medicine and Surgery to Wang, a Veterans Administration merit grant to Feldman, a Welch Foundation grant F-1319 and NSF grant CBET-0968038 to Johnston, and the Department of Energy Center for Frontiers of Subsurface Energy Security. NR 55 TC 3 Z9 3 U1 1 U2 9 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0196-8092 EI 1096-9101 J9 LASER SURG MED JI Lasers Surg. Med. PD JAN PY 2012 VL 44 IS 1 BP 49 EP 59 DI 10.1002/lsm.21153 PG 11 WC Dermatology; Surgery SC Dermatology; Surgery GA 875ZS UT WOS:000299076500007 ER PT J AU Sun, F Park, NS Roff, LL Klemmack, DL Parker, M Koenig, HG Sawyer, P Allman, RM AF Sun, Fei Park, Nan S. Roff, Lucinda L. Klemmack, David L. Parker, Michael Koenig, Harold G. Sawyer, Patricia Allman, Richard M. TI Predicting the trajectories of depressive symptoms among southern community-dwelling older adults: The role of religiosity SO AGING & MENTAL HEALTH LA English DT Article DE depressive symptoms; HLM; religiosity; trajectories ID MENTAL-HEALTH; PHYSICAL HEALTH; SOCIAL SUPPORT; RISK-FACTORS; SPIRITUALITY; INVOLVEMENT; PREVALENCE; CARE; SERVICES AB Background: This study examined the effects of religiosity on the trajectories of depressive symptoms in a sample of community-dwelling older adults over a four-year period in a Southern state in the US. Methods: Data from the University of Alabama at Birmingham (UAB) Study of Aging were analyzed using a hierarchical linear modeling (HLM) method. This study involved 1000 participants aged 65 and above (M age = 75 at baseline, SD = 5.97) and data were collected annually from 1999 to 2003. The Geriatric Depression Scale measured depressive symptoms; the Duke University Religion Index measured religious service attendance, prayer, and intrinsic religiosity; and control variables included sociodemographics, health, and social and economic factors. Results: The HLM analysis indicated a curvilinear trajectory of depressive symptoms over time. At baseline, participants who attended religious services more frequently tended to report fewer depressive symptoms. Participants with the highest levels of intrinsic religiosity at baseline experienced a steady decline in the number of depressive symptoms over the four-year period, while those with lower levels of intrinsic religiosity experienced a short-term decline followed by an increase in the number of depressive symptoms. Implications: In addition to facilitating access to health, social support and financial resources for older adults, service professionals might consider culturally appropriate, patient-centered interventions that boost the salutary effects of intrinsic religiosity on depressive symptoms. C1 [Sun, Fei] Arizona State Univ, Sch Social Work, Phoenix, AZ 85069 USA. [Park, Nan S.] Univ S Florida, Sch Social Work, Tampa, FL USA. [Roff, Lucinda L.; Klemmack, David L.; Parker, Michael] Univ Alabama, Sch Social Work, Tuscaloosa, AL USA. [Koenig, Harold G.] Duke Univ, Med Ctr, Durham, NC 27706 USA. [Sawyer, Patricia] Univ Alabama, Ctr Aging, Birmingham, AL USA. [Allman, Richard M.] Birmingham VA Med Ctr, Birmingham, AL USA. [Allman, Richard M.] Birmingham Atlanta VA Geriatr Res Educ & Clin Ctr, Birmingham, AL USA. RP Sun, F (reprint author), Arizona State Univ, Sch Social Work, Phoenix, AZ 85069 USA. EM fei.sun.1@asu.edu RI Koenig, Harold/F-7379-2011 FU National Institute on Aging [R01 AG15062, P30 AG031054] FX The project described was supported in part from grants R01 AG15062 and P30 AG031054 from the National Institute on Aging. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute on Aging or the National Institutes of Health. The authors also acknowledge the assistance of the John A. Harford Foundation's Geriatric Social Work Faculty Scholars Program. NR 48 TC 13 Z9 13 U1 1 U2 10 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 1360-7863 J9 AGING MENT HEALTH JI Aging Ment. Health PY 2012 VL 16 IS 2 BP 189 EP 198 DI 10.1080/13607863.2011.602959 PG 10 WC Geriatrics & Gerontology; Gerontology; Psychiatry SC Geriatrics & Gerontology; Psychiatry GA 909BG UT WOS:000301536400008 PM 22032625 ER PT J AU Tripathi, M Vibha, D Gupta, P Bhatia, R Srivastava, MVP Vivekanandhan, S Singh, MB Prasad, K Dergalust, S Mendez, MF AF Tripathi, Manjari Vibha, Deepti Gupta, Praveen Bhatia, Rohit Srivastava, M. V. Padma Vivekanandhan, S. Singh, Mamta Bhushan Prasad, Kameshwar Dergalust, Sunita Mendez, Mario F. TI Risk factors of dementia in North India: a case-control study SO AGING & MENTAL HEALTH LA English DT Article DE risk factors; dementia; diet; life style; apolipoprotein E ID INCIDENT ALZHEIMER-DISEASE; MILD COGNITIVE IMPAIRMENT; VASCULAR DEMENTIA; PROSPECTIVE COHORT; POPULATION; HOMOCYSTEINE; DECLINE; PREVALENCE; POLYMORPHISM; CHOLESTEROL AB Objective: The prevalence of dementia in northern India is among the lowest in the world but reasons are unclear. The aim of the study was to evaluate the risk and protective factors for dementia in North India. Methods: In a case-control study, we investigated demographic, medical, genetic, dietary, lifestyle, and sociocultural protective and risk factors associated with dementia. Results: 150 patients of dementia (118 males and 32 females) and 150 healthy controls (112 males and 38 females) were included in the study. Diabetes, depression, hyperhomocysteinemia, hyperlipidemia, APOE epsilon 4 gene, BMI, use of saturated fatty acids, pickles in diet, urban living, and lack of exercise were associated with independent risk of dementia. Various dietary factors and sociocultural factors, like cognitively stimulating activities, active socialization, living in joint families, increased intake of polyunsaturated fats, fruits, and salads conferred protection against dementia. Conclusions: Dietary, lifestyle, and sociocultural interventions may be protective against dementia. C1 [Tripathi, Manjari; Vibha, Deepti; Gupta, Praveen; Bhatia, Rohit; Srivastava, M. V. Padma; Singh, Mamta Bhushan; Prasad, Kameshwar] All India Inst Med Sci, Dept Neurol, New Delhi, India. [Vivekanandhan, S.] All India Inst Med Sci, Dept Neurobiochem, New Delhi, India. [Dergalust, Sunita] W Los Angeles VA Healthcare Ctr, Los Angeles, CA USA. [Mendez, Mario F.] Greater Los Angeles VA Med Ctr, UCLA Sch Med, Neurobehav Unit, Los Angeles, CA USA. RP Tripathi, M (reprint author), All India Inst Med Sci, Dept Neurol, New Delhi, India. EM manjari.tripathi@gmail.com NR 50 TC 10 Z9 10 U1 2 U2 21 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 1360-7863 J9 AGING MENT HEALTH JI Aging Ment. Health PY 2012 VL 16 IS 2 BP 228 EP 235 DI 10.1080/13607863.2011.583632 PG 8 WC Geriatrics & Gerontology; Gerontology; Psychiatry SC Geriatrics & Gerontology; Psychiatry GA 909BG UT WOS:000301536400012 PM 21714688 ER PT J AU Curtis, AR Oaklander, AL Johnson, A Yosipovitch, G AF Curtis, Ashley R. Oaklander, Anne L. Johnson, Annette Yosipovitch, Gil TI Trigeminal Trophic Syndrome from Stroke An Under-Recognized Central Neuropathic Itch Syndrome SO AMERICAN JOURNAL OF CLINICAL DERMATOLOGY LA English DT Article ID NASAL ULCERATION; PAIN; MECHANISMS; DIAGNOSIS AB Trigeminal trophic syndrome (TTS) is the historic name for neuropathic self-induced facial ulceration from abnormal sensory symptoms leading to uncontrolled scratching. Anatomic co-localization of sensory loss (numbness) plus neuropathic itch and pain permits painless scratching. If the itch is severe, some patients will scratch to the point of causing self-injury. Patients may be unaware or may conceal the fact that their lesions are self-induced and thus the diagnosis presents a clinical challenge. Many cases remain undiagnosed, leading to unnecessary and ineffective tests, procedures, and prescribing. We document a patient with a central cause of TTS - multiple cerebral vascular accidents and summarize the presentation, pathogenesis, and treatment options. C1 [Curtis, Ashley R.; Yosipovitch, Gil] Wake Forest Univ, Sch Med, Dept Dermatol, Winston Salem, NC 27104 USA. [Johnson, Annette] Wake Forest Univ, Baptist Med Ctr, Dept Radiol, Winston Salem, NC 27104 USA. [Oaklander, Anne L.] Harvard Univ, Sch Med, Dept Neurol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Oaklander, Anne L.] Harvard Univ, Sch Med, Dept Pathol, Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Yosipovitch, G (reprint author), Wake Forest Univ, Sch Med, Dept Dermatol, 4618 Country Club Rd, Winston Salem, NC 27104 USA. EM gyosipov@wfubmc.edu FU Public Health Service [K24NS59892] FX This case report was supported in part by the Public Health Service (K24NS59892, PI Oaklander). The authors have no conflicts of interest that are directly relevant to the content of this case report. NR 16 TC 6 Z9 6 U1 0 U2 6 PU ADIS INT LTD PI AUCKLAND PA 41 CENTORIAN DR, PRIVATE BAG 65901, MAIRANGI BAY, AUCKLAND 1311, NEW ZEALAND SN 1175-0561 J9 AM J CLIN DERMATOL JI Am. J. Clin. Dermatol. PY 2012 VL 13 IS 2 BP 125 EP 128 PG 4 WC Dermatology SC Dermatology GA 910EG UT WOS:000301619400005 PM 22220970 ER PT J AU Ezra, N Binder, SW Behroozan, D AF Ezra, Navid Binder, Scott W. Behroozan, Daniel TI Plasma Cell Balanitis Presenting in a Patient with a History of Syphilis SO AMERICAN JOURNAL OF CLINICAL DERMATOLOGY LA English DT Article ID PIMECROLIMUS 1-PERCENT CREAM; CARBON-DIOXIDE LASER; ZOONS BALANITIS; TOPICAL TACROLIMUS; GLANS-PENIS; CIRCUMCISION; ERYTHROPLASIA; CARCINOMA; VULVITIS; QUEYRAT AB Plasma cell balanitis (PCB), also knows as Zoon balanitis, is a benign asymptomatic but chronic and erosive inflammatory condition of the glans penis and prepuce that generally affects uncircumcised men in later years. Clinical presentation involves a single, shiny, well defined reddish patch. We describe the first case of PCB ever reported in a patient with a previous history of syphilis, and include a review of the current literature. A 57-year-old Hispanic man with a remote history of syphilis presented with a 6-month nonhealing, granulating ulcer of the foreskin and glans penis that had been repeatedly mistaken for syphilis and treated unsuccessfully with circumcision 3 weeks previously. Biopsy of the glans penis demonstrated sections with denuded chronic granulation tissue showing a fibrotic stroma with numerous blood vessels and a mixed inflammatory infiltrate including scattered plasma cells. It is important to differentiate PCB from a syphilitic chancre in a patient presenting with a nonhealing penile lesion. This case report demonstrates that these entities may be seen in the same patient at different times. C1 [Behroozan, Daniel] Dermatol Inst So Calif, Santa Monica, CA 90405 USA. [Ezra, Navid; Behroozan, Daniel] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Div Dermatol, Los Angeles, CA 90095 USA. [Binder, Scott W.] Univ Calif Los Angeles, David Geffen Sch Med, Div Dermatopathol, Dept Pathol & Lab Med, Los Angeles, CA 90095 USA. [Behroozan, Daniel] W Los Angeles Vet Adm Med Ctr, Dermatol Serv, Los Angeles, CA USA. RP Behroozan, D (reprint author), Dermatol Inst So Calif, 2221 Lincoln Blvd,Suite 100, Santa Monica, CA 90405 USA. EM db@dermsurgery.net NR 37 TC 1 Z9 3 U1 0 U2 1 PU ADIS INT LTD PI AUCKLAND PA 41 CENTORIAN DR, PRIVATE BAG 65901, MAIRANGI BAY, AUCKLAND 1311, NEW ZEALAND SN 1175-0561 J9 AM J CLIN DERMATOL JI Am. J. Clin. Dermatol. PY 2012 VL 13 IS 2 BP 129 EP 133 PG 5 WC Dermatology SC Dermatology GA 910EG UT WOS:000301619400006 PM 21992223 ER PT J AU Bloom, DE Canning, D Shenoy, ES AF Bloom, David E. Canning, David Shenoy, Erica S. TI The effect of vaccination on children's physical and cognitive development in the Philippines SO APPLIED ECONOMICS LA English DT Article DE vaccination; education; health; human capital; matching ID DEVELOPING-COUNTRIES; FILIPINO CHILDREN; CHILDHOOD; HEALTH; INFECTION; SKILLS; PERFORMANCE; BANGLADESH; NUTRITION; MORTALITY AB We use data from the Cebu Longitudinal Health and Nutrition Survey (CLHNS) in the Philippines to link vaccination in the first 2 years of life with later physical and cognitive development in children. We use propensity score matching to estimate the causal effect of vaccination on child development. We find no effect of vaccination on later height or weight, but full childhood vaccination for measles, polio, Tuberculosis (TB), Diphtheria, Pertussis and Tetanus (DPT) significantly increases cognitive test scores relative to matched children who received no vaccinations. The size of the effect is large, raising test scores, on average, by about half an SD. C1 [Bloom, David E.; Canning, David] Harvard Univ, Harvard Sch Publ Hlth, Boston, MA 02115 USA. [Shenoy, Erica S.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Shenoy, Erica S.] Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Canning, D (reprint author), Harvard Univ, Harvard Sch Publ Hlth, Boston, MA 02115 USA. EM dcanning@hsph.harvard.edu RI Canning, David/A-1917-2008 NR 36 TC 10 Z9 10 U1 1 U2 6 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 0003-6846 J9 APPL ECON JI Appl. Econ. PY 2012 VL 44 IS 21 BP 2777 EP 2783 DI 10.1080/00036846.2011.566203 PG 7 WC Economics SC Business & Economics GA 909CR UT WOS:000301540200010 ER PT J AU Lang, RM Badano, LP Tsang, W Adams, DH Agricola, E Buck, T Faletra, FF Franke, A Hung, JD de Isla, LP Kamp, O Kasprzak, JD Lancellotti, P Marwick, TH McCulloch, ML Monaghan, MJ Nihoyannopoulos, P Pandian, NG Pellikka, PA Pepi, M Roberson, DA Shernan, SK Shirali, GS Sugeng, L Ten Cate, FJ Vannan, MA Zamorano, JL Zoghbi, WA AF Lang, Roberto M. Badano, Luigi P. Tsang, Wendy Adams, David H. Agricola, Eustachio Buck, Thomas Faletra, Francesco F. Franke, Andreas Hung, Judy Perez de Isla, Leopoldo Kamp, Otto Kasprzak, Jaroslaw D. Lancellotti, Patrizio Marwick, Thomas H. McCulloch, Marti L. Monaghan, Mark J. Nihoyannopoulos, Petros Pandian, Natesa G. Pellikka, Patricia A. Pepi, Mauro Roberson, David A. Shernan, Stanton K. Shirali, Girish S. Sugeng, Lissa Ten Cate, Folkert J. Vannan, Mani A. Luis Zamorano, Jose Zoghbi, William A. CA Amer Soc Echocardiography Amer Soc Echocardiography European Assoc Echocardiography TI EAE/ASE Recommendations for Image Acquisition and Display Using Three-Dimensional Echocardiography SO EUROPEAN HEART JOURNAL-CARDIOVASCULAR IMAGING LA English DT Article DE Echocardiography; Two-dimensional; Three-dimensional; Transthoracic; Transesophageal ID DOBUTAMINE-STRESS-ECHOCARDIOGRAPHY; LEFT-VENTRICULAR VOLUMES; CARDIAC MAGNETIC-RESONANCE; VENA CONTRACTA AREA; CORONARY-ARTERY-DISEASE; LEFT ATRIAL APPENDAGE; AORTIC-VALVE AREA; 3D TRANSESOPHAGEAL ECHOCARDIOGRAPHY; FUNCTIONAL TRICUSPID REGURGITATION; COLOR DOPPLER-ECHOCARDIOGRAPHY C1 [Lang, Roberto M.; Tsang, Wendy] Univ Chicago, Chicago, IL 60637 USA. [Badano, Luigi P.] Univ Padua, Padua, Italy. [Adams, David H.] Mt Sinai Med Ctr, New York, NY 10029 USA. [Agricola, Eustachio] Hosp San Raffaele, I-20132 Milan, Italy. [Buck, Thomas] Univ Duisburg Essen, Essen, Germany. [Faletra, Francesco F.] Fdn Cardioctr Ticino, Lugano, Switzerland. [Franke, Andreas] Klinikum Reg Hannover Siloah, Hannover, Germany. [Hung, Judy] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Perez de Isla, Leopoldo; Luis Zamorano, Jose] Univ Clin San Carlos, Madrid, Spain. [Kamp, Otto] Vrije Univ Amsterdam, Med Ctr, Amsterdam, Netherlands. [Kasprzak, Jaroslaw D.] Med Univ Lodz, Lodz, Poland. [Lancellotti, Patrizio] Univ Liege, Liege, Belgium. [Marwick, Thomas H.] Cleveland Clin, Cleveland, OH 44106 USA. [McCulloch, Marti L.; Zoghbi, William A.] Methodist Hosp, Methodist DeBakey Heart & Vasc Ctr, Houston, TX 77030 USA. [Monaghan, Mark J.] Kings Coll Hosp London, London, England. [Nihoyannopoulos, Petros] Univ London Imperial Coll Sci Technol & Med, London, England. [Pandian, Natesa G.] Tufts Univ, Med Ctr, Boston, MA 02111 USA. [Pellikka, Patricia A.] Mayo Clin, Rochester, MN USA. [Pepi, Mauro] IRCCS, Ctr Cardiol Monzino, Milan, Italy. [Roberson, David A.] Heart Inst Children, Oak Lawn, IL USA. [Shernan, Stanton K.] Harvard Univ, Sch Med, Boston, MA USA. [Shirali, Girish S.] Med Univ S Carolina, Charleston, SC 29425 USA. [Sugeng, Lissa] Yale Univ, New Haven, CT USA. [Ten Cate, Folkert J.] Erasmus MC, Rotterdam, Netherlands. [Vannan, Mani A.] ASE Writing Grp, Morrisville, NC USA. RP Lang, RM (reprint author), Amer Soc Echocardiog, 2100 Gateway Ctr Blvd,Suite 310, Morrisville, NC 27560 USA. RI Marwick, Thomas/C-7261-2013; Kasprzak, Jaroslaw/S-4496-2016; OI Marwick, Thomas/0000-0001-9065-0899; Badano, Luigi/0000-0002-0379-3283 NR 153 TC 129 Z9 133 U1 1 U2 16 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 2047-2404 J9 EUR HEART J-CARD IMG JI Eur. Heart J.-Cardiovasc. Imaging PD JAN PY 2012 VL 13 IS 1 BP 1 EP 46 DI 10.1093/ehjci/jer316 PG 46 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 904ZB UT WOS:000301237900002 PM 22275509 ER PT J AU Tournoux, F Singh, JP Chan, RC Chen-Tournoux, A McCarty, D Manzke, R Ruskin, JN Semigran, M Heist, EK Moore, S Picard, MH Weyman, AE AF Tournoux, Francois Singh, Jagmeet P. Chan, Raymond C. Chen-Tournoux, Annabel McCarty, David Manzke, Robert Ruskin, Jeremy N. Semigran, Marc Heist, E. Kevin Moore, Stephanie Picard, Michael H. Weyman, Arthur E. TI Absence of left ventricular apical rocking and atrial-ventricular dyssynchrony predicts non-response to cardiac resynchronization therapy SO EUROPEAN HEART JOURNAL-CARDIOVASCULAR IMAGING LA English DT Article DE Heart failure; Echocardiography; Pacing; Mechanics; CRT ID IDIOPATHIC DILATED CARDIOMYOPATHY; HEART-FAILURE PATIENTS; ISCHEMIC CARDIOMYOPATHY; ANATOMICAL INFORMATION; MULTISITE STIMULATION; INTEGRATIVE APPROACH; DOPPLER; ECHOCARDIOGRAPHY; ASYNCHRONY; TISSUE AB Aims Current imaging techniques attempt to identify responders to cardiac resynchronization therapy (CRT). However, because CRT response may depend upon several factors, it may be clinically more useful to identify patients for whom CRT would not be beneficial even under optimal conditions. We aimed to determine the negative predictive value of a composite echocardiographic index evaluating atrial-ventricular dyssynchrony (AV-DYS) and intraventricular dyssynchrony. Methods and results Subjects with standard indications for CRT underwent echo before and during the month following device implantation. AV-DYS was defined as a percentage of left ventricular (LV) filling time over the cardiac cycle. AV-DYS, which produces a characteristic rocking of the LV apex, was quantified as the percentage of the cardiac cycle over which tissue Doppler-derived displacement curves of the septal and lateral walls showed discordance. CRT responder status was determined based on the early haemodynamic response to CRT (intra-individual improvement.25% in the Doppler-derived LV dP/dt). Among 40 patients, optimal cut-points predicting CRT response were 31% for LV apical rocking and 39% for AV-DYS. The presence of either apical rocking.31% or AV-DYS = 39% had a sensitivity of 95%, specificity of 80%, positive predictive value of 83%, and a negative predictive value of 94% for CRT response. Conclusion After pre-selection of candidates for CRT by QRS duration, application of a simple composite echocardiographic index may exclude patients who would be non-responders to CRT and thus improve the global rate of therapy success. C1 [Tournoux, Francois; Singh, Jagmeet P.; Chen-Tournoux, Annabel; McCarty, David; Ruskin, Jeremy N.; Semigran, Marc; Heist, E. Kevin; Moore, Stephanie; Picard, Michael H.; Weyman, Arthur E.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA 02115 USA. [Tournoux, Francois] Massachusetts Gen Hosp, Cardiac Ultrasound Lab, Boston, MA 02114 USA. [Chan, Raymond C.; Manzke, Robert] Philips Res N Amer, Boston, MA USA. RP Tournoux, F (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA 02115 USA. EM francois.tournoux@cardiopixel.com OI Picard, Michael/0000-0002-9264-3243 FU Harvard Medical School FX This work was supported the Harvard Medical School Harold M. English Research Grant (F.T.). NR 36 TC 11 Z9 11 U1 2 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 2047-2404 J9 EUR HEART J-CARD IMG JI Eur. Heart J.-Cardiovasc. Imaging PD JAN PY 2012 VL 13 IS 1 BP 86 EP 94 DI 10.1093/ehjci/jer167 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 904ZB UT WOS:000301237900009 PM 21921079 ER PT J AU Shazly, TA Al-Hussaini, AK AF Shazly, Tarek A. Al-Hussaini, A. K. TI Pediatric Ocular Injuries From Airsoft Toy Guns SO JOURNAL OF PEDIATRIC OPHTHALMOLOGY & STRABISMUS LA English DT Article ID AIR GUN; CHILDREN; BB AB Purpose: To report ocular injuries caused by airsoft guns in children. Methods: A retrospective chart review of pediatric patients who sustained ocular injuries related to airsoft guns between November 2005 and December 2007. Place of trauma, presenting symptoms and signs, surgical interventions performed, and final visual outcome were reviewed. Results: Thirty-two patients with a mean age of 8.8 +/- 4.0 years (range: 1.5 to 18 years) were examined; 28 were boys (87.5%). Presenting visual acuity ranged from hand motions to 20/20 and could not be assessed in 2 patients. Hyphema was a common finding that was present in 24 cases, corneal abrasions were present in 10 cases, and raised intraocular pressure was present in 7 cases. Seven patients presented with traumatic cataract, and two had iridodialysis. Immediate surgical intervention was performed in 7 patients and 7 patients were scheduled for elective surgery. The patients presented after an average of 1.9 +/- 1.9 days (range: 4 hours to 6 days) after the injury. Average follow-up was 18 days (range: 7 days to 5 months). Final visual acuity was 20/200 or worse in 5 patients, 20/40 or better in 23 patients, and could not be assessed in 2 cases. Conclusion: Airsoft guns can cause a variety of serious injuries, sometimes necessitating operative intervention. The long-term morbidity from some of these injuries is significant. Airsoft guns are capable of inflicting serious and permanent ocular damage. C1 [Shazly, Tarek A.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA USA. [Shazly, Tarek A.; Al-Hussaini, A. K.] Assiut Univ Hosp, Dept Ophthalmol, Assiut, Egypt. RP Shazly, TA (reprint author), 20 Pondmeadow Dr,Ste 203, Reading, MA 01867 USA. EM shazlyt@gmail.com OI A Shazly, Tarek/0000-0002-4561-1871 NR 18 TC 2 Z9 2 U1 1 U2 2 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 USA SN 0191-3913 J9 J PEDIAT OPHTH STRAB JI J. Pediatr. Ophthalmol. Strabismus. PD JAN-FEB PY 2012 VL 49 IS 1 BP 54 EP 57 DI 10.3928/01913913-20110118-05 PG 4 WC Ophthalmology; Pediatrics SC Ophthalmology; Pediatrics GA 905VJ UT WOS:000301303900012 PM 21261240 ER PT J AU Sadaka, A Cherfan, DG Melki, SA AF Sadaka, Ama Cherfan, Daniel G. Melki, Samir A. TI Inadvertent LASIK Flap Creation Over a Soft Contact Lens SO JOURNAL OF REFRACTIVE SURGERY LA English DT Article AB PURPOSE: To report the findings and outcomes in two cases in which a contact lens was inadvertently present during creation of a LASIK corneal flap. METHODS: Interventional case report. RESULTS: A soft contact lens blocked the successful creation of the corneal flap with a femtosecond laser in one patient. Repeat surgery 1 week later resulted in a normal flap. In the second patient, a thin but normal-shaped flap was successfully created using a microkeratome despite the presence of a soft contact lens in the patient's eye. No adverse effect on vision was noted in either case. CONCLUSIONS: Refractive surgeons are encouraged to establish or review current procedures to ensure adequate contact lens removal prior to LASIK surgery, as it may result in an aborted procedure or a potentially thin and/or irregular corneal flap. [J Refract Surg. 2012; 28(1): 74-76.] doi:10.3928/1081597X-20111102-01 C1 [Sadaka, Ama; Melki, Samir A.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA USA. [Cherfan, Daniel G.; Melki, Samir A.] Boston Eye Grp, Boston, MA USA. RP Melki, SA (reprint author), 1101 Beacon St,6W, Brookline, MA 02446 USA. EM samir_melki@meei.harvard.edu NR 1 TC 1 Z9 1 U1 0 U2 2 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 USA SN 1081-597X J9 J REFRACT SURG JI J. Refractive Surg. PD JAN PY 2012 VL 28 IS 1 BP 74 EP 76 DI 10.3928/1081597X-20111102-01 PG 3 WC Ophthalmology; Surgery SC Ophthalmology; Surgery GA 905VX UT WOS:000301305400015 PM 22074465 ER PT J AU Rosenthal, P Borsook, D AF Rosenthal, Perry Borsook, David TI The Corneal Pain System. Part I: The Missing Piece of the Dry Eye Puzzle SO OCULAR SURFACE LA English DT Article DE allodynia; corneal pain; dry eye; hyperalgesia; inflammation; nociceptive network; pain ID VIVO CONFOCAL MICROSCOPY; PRIMARY SENSORY NEURONS; CONTACT-LENS WEAR; NEUROPATHIC PAIN; TEAR PRODUCTION; SPINAL-CORD; SECONDARY HYPERALGESIA; REFRACTIVE SURGERY; DESICCATING STRESS; CENTRAL MECHANISMS AB The traditional model of dry eye disease based on tear deficiency has presented us with many unanswered questions. Recent studies support the notion that dry eyelike symptoms represent non-specific corneal pain and provide new insights into the mechanisms that sustain the integrity of the optical tear layer. Thus, this enigmatic disease can be viewed with a new perspective, which involves the dysfunctional corneal pain system as a central pathogenetic feature of a series of disorders collectively known today as dry eye. C1 [Rosenthal, Perry] Boston Fdn Sight, Needham, MA 02494 USA. [Borsook, David] Harvard Univ, Sch Med, Ctr Pain & Brain, McLean Hosp, Boston, MA USA. [Borsook, David] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Pain & Brain, Boston, MA USA. [Borsook, David] Harvard Univ, Childrens Hosp, Sch Med, Ctr Pain & Brain, Boston, MA 02115 USA. RP Rosenthal, P (reprint author), Boston Fdn Sight, 464 Hillside Ave, Needham, MA 02494 USA. EM prosenthal@bostonsight.org FU Boston Foundation for Sight FX Supported by The Boston Foundation for Sight. NR 130 TC 57 Z9 57 U1 0 U2 7 PU ETHIS COMMUNICATINS, INC PI NEW YORK PA 75 MAIDEN LANE, STE 408, NEW YORK, NY 10038 USA SN 1542-0124 J9 OCUL SURF JI Ocul. Surf. PD JAN PY 2012 VL 10 IS 1 BP 2 EP 14 PG 13 WC Ophthalmology SC Ophthalmology GA 907EK UT WOS:000301400400002 PM 22330055 ER PT J AU Dichter, ME Gelles, RJ AF Dichter, Melissa E. Gelles, Richard J. TI Women's Perceptions of Safety and Risk Following Police Intervention for Intimate Partner Violence SO VIOLENCE AGAINST WOMEN LA English DT Article DE battering; intimate partner violence; revictimization ID WIFE ASSAULT RECIDIVISM; DOMESTIC VIOLENCE; PROTECTIVE FACTORS; BATTERED WOMEN; ABUSE; VICTIMIZATION; BEHAVIOR; VICTIMS; SHELTER; REABUSE AB Police intervention is a primary response to intimate partner violence (IPV) but does not guarantee a victim's future safety. This study sought to identify factors associated with IPV survivors' perceptions of safety and risk of revictimization following police intervention. One hundred sixty-four women completed a questionnaire, and 11 of those women also took part in qualitative interviews. The findings revealed that feeling unsafe and perceiving oneself to be at risk of future violence is associated with experiencing particular forms of IPV, including battering, lethality threats, and sexual violence. Having support from others and distance from the partner helps women feel safe. C1 [Dichter, Melissa E.] Philadelphia VA Med Ctr, Ctr Hlth Equ Res & Promot, Philadelphia, PA 19104 USA. [Gelles, Richard J.] Univ Penn, Sch Social Policy & Practice, Philadelphia, PA 19104 USA. RP Dichter, ME (reprint author), Philadelphia VA Med Ctr, Ctr Hlth Equ Res & Promot, 3900 Woodland Ave, Philadelphia, PA 19104 USA. EM mdichter@sp2.upenn.edu FU NCIPC CDC HHS [1R49CE001226-01, R49 CE001226] NR 50 TC 12 Z9 12 U1 6 U2 31 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1077-8012 J9 VIOLENCE AGAINST WOM JI Violence Against Women PD JAN PY 2012 VL 18 IS 1 BP 44 EP 63 DI 10.1177/1077801212437016 PG 20 WC Women's Studies SC Women's Studies GA 906OJ UT WOS:000301355300004 PM 22411298 ER PT J AU Gaffo, AL Saag, KG AF Gaffo, Angelo L. Saag, Kenneth G. TI Drug Treatment of Hyperuricemia to Prevent Cardiovascular Outcomes Are We There Yet? SO AMERICAN JOURNAL OF CARDIOVASCULAR DRUGS LA English DT Article ID SERUM URIC-ACID; NUTRITION EXAMINATION SURVEY; 3RD NATIONAL-HEALTH; BLOOD-PRESSURE; GLOMERULAR HYPERTENSION; HEART-FAILURE; INCIDENT HYPERTENSION; METABOLIC SYNDROME; DECISION-ANALYSIS; OXIDATIVE STRESS AB Data supporting an association between high levels of serum urate and cardiovascular disease have continued to emerge. Basic science data, small clinical trials, and epidemiologic studies have provided support for the idea of a true causal effect. In this paper, we present evidence about the association between hyperuricemia and selected cardiovascular diseases. Although data generated so far compellingly support pharmacologic urate-lowering therapy in selected cases with high cardiovascular risk, further evidence is necessary before widely advocating this approach to prevent cardiovascular outcomes putatively associated with hyperuricemia. C1 [Gaffo, Angelo L.] Birmingham VA Med Ctr, Birmingham, AL USA. [Gaffo, Angelo L.; Saag, Kenneth G.] Univ Alabama, Div Clin Immunol & Rheumatol, Birmingham, AL 35294 USA. RP Saag, KG (reprint author), FOT 820,1530 3rd Ave S, Birmingham, AL 35294 USA. EM ksaag@uab.edu FU Takeda; Savient; Merck FX Dr Saag is a consultant to Takeda, Savient, and Merck. He has received research grants from Takeda, Savient, and Merck. Dr Gaffo has no conflicts of interest to declare. NR 58 TC 6 Z9 7 U1 0 U2 2 PU ADIS INT LTD PI AUCKLAND PA 41 CENTORIAN DR, PRIVATE BAG 65901, MAIRANGI BAY, AUCKLAND 1311, NEW ZEALAND SN 1175-3277 J9 AM J CARDIOVASC DRUG JI Am. J. Cardiovasc. Drugs PY 2012 VL 12 IS 1 BP 1 EP 6 PG 6 WC Cardiac & Cardiovascular Systems; Pharmacology & Pharmacy SC Cardiovascular System & Cardiology; Pharmacology & Pharmacy GA 905NE UT WOS:000301278100001 PM 22204636 ER PT J AU Ingmanson, EJ May-Benson, TA Braccini, S Porton, I Hunnicutt, T Bauman, ML AF Ingmanson, Ellen J. May-Benson, Teresa A. Braccini, Stephanie Porton, Ingrid Hunnicutt, Terri Bauman, Margaret L. TI Application of human-based sensory integration therapy for improving the well-being of a captive chimpanzee (Pan troglodytes). SO AMERICAN JOURNAL OF PHYSICAL ANTHROPOLOGY LA English DT Meeting Abstract CT 81st Annual Meeting of the American-Association-of-Physical-Anthropologists CY 2012 CL Portland, OR SP Amer Assoc Phys Anthropol C1 [Ingmanson, Ellen J.] Bridgewater State Univ, Bridgewater, MA USA. [Bauman, Margaret L.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Bauman, Margaret L.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0002-9483 J9 AM J PHYS ANTHROPOL JI Am. J. Phys. Anthropol. PY 2012 VL 147 SU 54 BP 172 EP 172 PG 1 WC Anthropology; Evolutionary Biology SC Anthropology; Evolutionary Biology GA 895LW UT WOS:000300498700410 ER PT J AU Goldfarb-Rumyantzev, AS Sandhu, GS Baird, B Barenbaum, A Yoon, JH Dimitri, N Koford, JK Shihab, F AF Goldfarb-Rumyantzev, Alexander S. Sandhu, Gurprataap S. Baird, Bradley Barenbaum, Anna Yoon, Joo Heung Dimitri, Noelle Koford, James K. Shihab, Fuad TI Effect of education on racial disparities in access to kidney transplantation SO CLINICAL TRANSPLANTATION LA English DT Article DE access to transplantation; education; outcome; race; racial and ethnic disparities; renal transplant ID RENAL-TRANSPLANTATION; SURVIVAL; OUTCOMES; RECIPIENT; DISEASE; GRAFT; LIVE AB Higher education level might result in reduced disparities in access to renal transplantation. We analyzed two outcomes: (i) being placed on the waiting list or transplanted without listing and (ii) transplantation in patients who were placed on the waiting list. We identified 3224 adult patients with end-stage renal disease (ESRD) in United States Renal Data System with education information available (mean age of ESRD onset of 57.1 +/- 16.2 yr old, 54.3% men, 64.2% white, and 50.4% diabetics). Compared to whites, fewer African Americans graduated from college (10% vs. 16.7%) and a higher percentage never graduated from the high school (38.6% vs. 30.8%). African American race was associated with reduced access to transplantation (hazard ratio [HR] 0.70, p < 0.001 for wait-listing/transplantation without listing; HR 0.58, p < 0.001 for transplantation after listing). African American patients were less likely to be wait-listed/transplanted in the three less-educated groups: HR 0.67 (p = 0.005) for those never completed high school, HR 0.76 (p = 0.02) for high school graduates, and HR 0.65 (p = 0.003) for those with partial college education. However, the difference lost statistical significance in those who completed college education (HR 0.75, p = 0.1). In conclusion, in comparing white and African American candidates, racial disparities in access to kidney transplantation do exist. However, they might be alleviated in highly educated individuals. C1 [Goldfarb-Rumyantzev, Alexander S.; Sandhu, Gurprataap S.] Beth Israel Deaconess Med Ctr, Div Nephrol, Boston, MA 02215 USA. [Yoon, Joo Heung] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med, Boston, MA USA. [Goldfarb-Rumyantzev, Alexander S.; Dimitri, Noelle] Beth Israel Deaconess Med Ctr, Transplant Inst, Boston, MA 02215 USA. [Baird, Bradley; Shihab, Fuad] Univ Utah, Sch Med, Div Nephrol & Hypertens, Salt Lake City, UT USA. [Barenbaum, Anna] Tel Aviv Univ, IL-69978 Tel Aviv, Israel. [Koford, James K.] Univ Utah, Writing Program, Div Undergrad Studies, Salt Lake City, UT USA. RP Goldfarb-Rumyantzev, AS (reprint author), Beth Israel Deaconess Med Ctr, Div Nephrol, 330 Brookline Ave,DA 517, Boston, MA 02215 USA. EM agoldfar@bidmc.harvard.edu NR 20 TC 16 Z9 16 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0902-0063 J9 CLIN TRANSPLANT JI Clin. Transplant. PD JAN-FEB PY 2012 VL 26 IS 1 BP 74 EP 81 DI 10.1111/j.1399-0012.2010.01390.x PG 8 WC Surgery; Transplantation SC Surgery; Transplantation GA 898DH UT WOS:000300715100021 PM 21198857 ER PT J AU Mariappan, MM AF Mariappan, Meenalakshmi M. TI Signaling Mechanisms in the Regulation of Renal Matrix Metabolism in Diabetes SO EXPERIMENTAL DIABETES RESEARCH LA English DT Review ID MESSENGER-RNA TRANSLATION; GLYCOGEN-SYNTHASE KINASE-3-BETA; ACTIVATED PROTEIN-KINASE; UPSTREAM BINDING-FACTOR; RICTOR-MTOR COMPLEX; BASEMENT-MEMBRANE; EPITHELIAL-CELLS; HIGH GLUCOSE; ANGIOTENSIN-II; MESANGIAL CELLS AB Renal hypertrophy and accumulation of extracellular matrix proteins are among cardinal manifestations of diabetic nephropathy. TGF beta system has been implicated in the pathogenesis of these manifestations. Among signaling pathways activated in the kidney in diabetes, mTOR- (mammalian target of rapamycin-) regulated pathways are pivotal in orchestrating high glucose-induced production of ECM proteins leading to functional and structural changes in the kidney culminating in adverse outcomes. Understanding signaling pathways that influence individual matrix protein expression could lead to the development of new interventional strategies. This paper will highlight some of the diverse components of the signaling network stimulated by hyperglycemia with an emphasis on extracellular matrix protein metabolism in the kidney in diabetes. C1 Univ Texas Hlth Sci Ctr San Antonio, Dept Med, Div Nephrol, S Texas Vet Healthcare Syst, San Antonio, TX 78229 USA. RP Mariappan, MM (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Med, Div Nephrol, S Texas Vet Healthcare Syst, MC7882,7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM malini@uthscsa.edu FU NIH; American Diabetes Association; Juvenile Diabetes Research Foundation; National Kidney Foundation of South and Central Texas; VA merit review program FX The author thanks his mentor Dr. B. S. Kasinath for critically reading the paper and for giving comments and advice. Work contained in this paper was supported by the NIH, VA merit review program, and American Diabetes Association awarded to B. S. Kasinath and Juvenile Diabetes Research Foundation and the National Kidney Foundation of South and Central Texas awarded to M. M. Mariappan. The author regrets that due to space limitations many seminal publications could not be cited. NR 115 TC 20 Z9 21 U1 0 U2 2 PU HINDAWI PUBLISHING CORPORATION PI NEW YORK PA 410 PARK AVENUE, 15TH FLOOR, #287 PMB, NEW YORK, NY 10022 USA SN 1687-5214 J9 EXP DIABETES RES JI Exp. Diabetes Res. PY 2012 AR 749812 DI 10.1155/2012/749812 PG 10 WC Endocrinology & Metabolism; Medicine, Research & Experimental SC Endocrinology & Metabolism; Research & Experimental Medicine GA 906NF UT WOS:000301351400001 ER PT J AU Hussain, M Javeed, A Ashraf, M Zhao, Y Mukhtar, MM Rehman, MU AF Hussain, Muzammal Javeed, Aqeel Ashraf, Muhammad Zhao, Yong Mukhtar, Muhammad Mahmood Rehman, Muti Ur TI Aspirin and immune system SO INTERNATIONAL IMMUNOPHARMACOLOGY LA English DT Review DE Aspirin; Autoimmunity; Immunosuppressant; NO-aspirin; Immune tolerance; Tolerogenic dendritic cells ID PITUITARY-ADRENAL AXIS; NF-KAPPA-B; REGULATORY T-CELLS; TRIGGERED LIPOXIN A(4); BLOOD MONONUCLEAR-CELLS; GINKGO-BILOBA EXTRACT; NCX-4016 NO-ASPIRIN; LOW-DOSE ASPIRIN; NITRIC-OXIDE; DENDRITIC CELLS AB The time-tested gradual exploration of aspirin's diverse pharmacological properties has made it the most reliable therapeutic agent worldwide. In addition to its well-argued anti-inflammatory effects, many new and exciting data have emerged regarding the role of aspirin in cells of the immune system and certain immunopathological states. For instance, aspirin induces tolerogenic activity in dendritic cells and determines the fate of naive T cells to regulatory phenotypes, which suggests its immunoregulatory potential in relevance to immune tolerance. It also displays some intriguing traits to modulate the innate and adaptive immune responses. In this article, the immunomodulatory relation of aspirin to different immune cells, such as neutrophils, macrophages, dendritic cells (DCs), natural killer (NK) cells, and the T and B lymphocytes has been highlighted. Moreover, the clinical prospects of aspirin in terms of autoimmunity, allograft rejection and immune tolerance have also been outlined. (C) 2011 Elsevier B.V. All rights reserved. C1 [Hussain, Muzammal; Javeed, Aqeel; Ashraf, Muhammad] Univ Vet & Anim Sci, Dept Pharmacol & Toxicol, Lahore 54600, Pakistan. [Zhao, Yong] Chinese Acad Sci, Transplantat Biol Res Div, State Key Lab Biomembrane & Membrane Biotechnol, Inst Zool, Beijing 100101, Peoples R China. [Mukhtar, Muhammad Mahmood] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Rehman, Muti Ur] Univ Vet & Anim Sci, Dept Pathol, Lahore 54600, Pakistan. RP Javeed, A (reprint author), Univ Vet & Anim Sci, Dept Pharmacol & Toxicol, Abdul Qadir Jilani Rd, Lahore 54600, Pakistan. EM aqeel.javeed@uvas.edu.pk OI Hussain, Muzammal/0000-0002-1117-5864 NR 164 TC 29 Z9 30 U1 1 U2 10 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1567-5769 EI 1878-1705 J9 INT IMMUNOPHARMACOL JI Int. Immunopharmacol. PD JAN PY 2012 VL 12 IS 1 BP 10 EP 20 DI 10.1016/j.intimp.2011.11.021 PG 11 WC Immunology; Pharmacology & Pharmacy SC Immunology; Pharmacology & Pharmacy GA 901LU UT WOS:000300969200002 PM 22172645 ER PT J AU Mizwicki, MT Menegaz, D Zhang, J Barrientos-Duran, A Tse, S Cashman, JR Griffin, PR Fiala, M AF Mizwicki, Mathew T. Menegaz, Danusa Zhang, Jun Barrientos-Duran, Antonio Tse, Stephen Cashman, John R. Griffin, Patrick R. Fiala, Milan TI Genomic and Nongenomic Signaling Induced by 1 alpha,25(OH)(2)-Vitamin D-3 Promotes the Recovery of Amyloid-beta Phagocytosis by Alzheimer's Disease Macrophages SO JOURNAL OF ALZHEIMERS DISEASE LA English DT Article DE Alzheimer's disease; amyloid-beta; chloride channel; ClC-3; curcumin; hydrogen-deuterium exchange; nongenomic; nuclear vitamin D receptor; phagocytosis; 1 alpha,25(OH)(2)-vitamin D-3 ID VITAMIN-D-RECEPTOR; CHLORIDE CHANNELS; ANION CHANNELS; PROTEIN-KINASE; ENSEMBLE MODEL; CELLS; CLC-3; THERAPEUTICS; PATHWAYS; CIC-3 AB Brain clearance of amyloid-beta (A beta(42)) by innate immune cells is necessary for maintenance of normal brain function. Phagocytosis of soluble A beta(42) by Alzheimer's disease (AD) macrophages is defective, recovered in all "Type I and Type II" AD patients by 1 alpha,25(OH)(2)-vitamin D-3 (1,25D3) and blocked by the nuclear vitamin D receptor (VDR) antagonist (23S)-25-dehydro-1 alpha(OH)-vitamin D-3-26,23-lactone (MK). Bisdemethoxycurcumin (BDC) is a VDR ligand and additive with 1,25D3 in promoting A beta(42) phagocytosis by Type I, but not by Type II macrophages. Here, we define the following intracellular mechanisms regulated by 1,25D3 that are associated with recovery of phagocytosis and consistent with the selectivity of BDC: 1) 1,25D3 potentiates a 4,4-diisothiocyanostilbene-2,2-disulfonic acid-sensitive chloride channel (i.e., ClC-3) currents in both Type I and II AD macrophages, but curcumin only potentiates the currents in Type I cells; 2) 1,25D3 is particularly effective in upregulating ClC-3 mRNA expression in Type II peripheral blood mononuclear cells (PBMCs) while both 1,25D3 and the BDC analog, C180, upregulate VDR mRNA, repressed by A beta(42) in Type II PBMCs; and 3) 1,25D3-induced A beta(42) phagocytosis is attenuated by the calcium-dependent ClC-3 blocker, inositol 3,4,5,6-tetraphosphate (IP4), in both AD Types and by the MEK1/2 inhibitor U0126 only in Type II macrophages. VDR hydrogen/deuterium exchange coupled mass spectrometry and computational results show differences between the abilities of 1,25D3 and curcuminoids to stabilize VDR helices associated with the regulation of gene transcription. The structure-function results provide evidence that 1,25D3 activation of VDR-dependent genomic and nongenomic signaling, work in concert to recover dysregulated innate immune function in AD. C1 [Mizwicki, Mathew T.; Menegaz, Danusa; Barrientos-Duran, Antonio] Univ Calif Riverside, Dept Biochem, Riverside, CA 92521 USA. [Zhang, Jun; Griffin, Patrick R.] Scripps Res Inst, Dept Mol Therapeut, Jupiter, FL USA. [Tse, Stephen; Fiala, Milan] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA. [Tse, Stephen; Fiala, Milan] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Cashman, John R.] Human BioMol Res Inst, San Diego, CA USA. RP Mizwicki, MT (reprint author), UCLA CHS, 650 Charles E Young Dr S,Room 23-338, Los Angeles, CA 90095 USA. EM mtmizwicki@gmail.com; fiala@mednet.ucla.edu FU Fundacion Alfonso Martin Escudero; NIH [DK-09012-048] FX A.B-D would like to acknowledge his post-doctoral fellowship supported by Fundacion Alfonso Martin Escudero. MTM would like to acknowledge support from Anthony W. Norman (NIH grant: DK-09012-048) and his mentorship. NR 50 TC 28 Z9 29 U1 0 U2 10 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 1387-2877 J9 J ALZHEIMERS DIS JI J. Alzheimers Dis. PY 2012 VL 29 IS 1 BP 51 EP 62 DI 10.3233/JAD-2011-110560 PG 12 WC Neurosciences SC Neurosciences & Neurology GA 903SB UT WOS:000301139000005 PM 22207005 ER PT J AU Ishii, S Streim, JE Saliba, D AF Ishii, Shinya Streim, Joel E. Saliba, Debra TI A Conceptual Framework for Rejection of Care Behaviors: Review of Literature and Analysis of Role of Dementia Severity SO JOURNAL OF THE AMERICAN MEDICAL DIRECTORS ASSOCIATION LA English DT Review DE Rejection of care; challenging behavior; disruptive behavior; conceptual framework; meta-analysis ID NURSING-HOME RESIDENTS; QUALITY-OF-LIFE; VERSION NPI-NH; MILD COGNITIVE IMPAIRMENT; LOWERED STRESS THRESHOLD; SKILL-BUILDING PROGRAM; E E4 ALLELE; ALZHEIMERS-DISEASE; NEUROPSYCHIATRIC SYMPTOMS; PSYCHOLOGICAL SYMPTOMS AB Rejection of care behaviors is common in the geriatric population, especially among patients with dementia. Nonetheless, the concept of rejection of care is not well defined and existing psychosocial theoretical models fall short of capturing complex relationships between factors associated with rejection of care. We propose a definition of rejection of care and develop a conceptual framework of rejection of care incorporating 7 components: intrinsic factors, match between needs and environmental resources, behavior state, antecedents, individual preferences, rejection of care behaviors, and consequences. A literature search yielded 55 studies that examined the associations between rejection of care and factors of the conceptual framework. We quantitatively synthesized studies focused on dementia severity and rejection of care. The literature review demonstrated that rejection of care is more prevalent among patients with dementia or functional impairment, associated with some mutable factors, and is triggered by specific antecedents in the context of daily personal care provision and associated with various adverse outcomes. The meta-analysis provided evidence that severe dementia is associated with higher likelihood of developing rejection of care behaviors compared with mild to moderate dementia. We also found that research on unmet needs, antecedents, and individual preferences has been scarce. The direction of further research is discussed. Copyright (C) 2012 - American Medical Directors Association, Inc. C1 [Ishii, Shinya; Saliba, Debra] VA Greater Los Angeles Healthcare Syst, VA Geriatr Res Educ & Clin Ctr, Los Angeles, CA 90073 USA. [Streim, Joel E.] Philadelphia Vet Affairs VA Med Ctr, Vet Integrated Serv Network 4 VISN 4, Mental Illness Res Educ & Clin Ctr MIRECC, Philadelphia, PA USA. [Streim, Joel E.; Saliba, Debra] Univ Penn, Dept Psychiat, Geriatr Psychiat Sect, Philadelphia, PA 19104 USA. [Saliba, Debra] VA HSR&D Ctr Excellence Study Healthcare Provider, Los Angeles, CA USA. [Saliba, Debra] UCLA JH Borun Ctr Gerontol Res, Los Angeles, CA USA. [Saliba, Debra] RAND Corp, Santa Monica, CA USA. RP Ishii, S (reprint author), VA Greater Los Angeles Healthcare Syst, VA Geriatr Res Educ & Clin Ctr, 11301 Wilshire Blvd,Bldg 220,Room 302, Los Angeles, CA 90073 USA. EM sishii@mednet.ucla.edu FU US Department of Veterans Affairs, Veterans Health Administration, VA Health Services Research & Development (HSR&D) Service through the VA Greater Los Angeles HSR&D Center of Excellence [SDR 03-217]; VA Office of Academic Affairs; Centers for Medicare & Medicaid Services FX This work was funded by the US Department of Veterans Affairs, Veterans Health Administration, VA Health Services Research & Development (HSR&D) Service through the VA Greater Los Angeles HSR&D Center of Excellence (Project # SDR 03-217), the VA Office of Academic Affairs, and the Centers for Medicare & Medicaid Services. NR 110 TC 13 Z9 13 U1 1 U2 13 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1525-8610 J9 J AM MED DIR ASSOC JI J. Am. Med. Dir. Assoc. PD JAN PY 2012 VL 13 IS 1 BP 11 EP U40 DI 10.1016/j.jamda.2010.11.004 PG 15 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA 898HT UT WOS:000300733100010 PM 21450222 ER PT J AU Castle, NG Wagner, LM Ferguson, JC Smith, ML Handler, SM AF Castle, Nicholas G. Wagner, Laura M. Ferguson, Jamie C. Smith, Mary Lindsey Handler, Steven M. TI Alcohol Misuse and Abuse in Assisted Living SO JOURNAL OF THE AMERICAN MEDICAL DIRECTORS ASSOCIATION LA English DT Letter C1 [Castle, Nicholas G.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Hlth Policy & Management, Pittsburgh, PA 15260 USA. [Wagner, Laura M.] Baycrest Geriatr Healthcare Syst, Kunin Lunenfeld Appl Res Unit, Toronto, ON, Canada. [Smith, Mary Lindsey] Univ Pittsburgh, Dept Psychiat, Mental Illness Res Educ & Clin Ctr, VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. [Handler, Steven M.] Univ Pittsburgh, Sch Med,Vet Affairs Pittsburgh Healthcare Syst, Dept Biomed Informat,Geriatr Res Educ & Clin Ctr,, LTC Hlth Informat Technol,UPMC Senior Communities, Pittsburgh, PA USA. RP Castle, NG (reprint author), Univ Pittsburgh, Grad Sch Publ Hlth, Dept Hlth Policy & Management, Pittsburgh, PA 15260 USA. OI Handler, Steven/0000-0002-3940-3224 FU AHRQ HHS [1 RO3 HS0165347-01A1] NR 3 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 1525-8610 J9 J AM MED DIR ASSOC JI J. Am. Med. Dir. Assoc. PD JAN PY 2012 VL 13 IS 1 BP E7 EP E7 DI 10.1016/j.jamda.2011.06.010 PG 1 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA 898HT UT WOS:000300733100004 PM 21764389 ER PT J AU Hanlon, JT Aspinall, SL AF Hanlon, Joseph T. Aspinall, Sherrie L. TI Renal Function Equations to Use to Guide Prescribing of Primarily Renally Cleared Medications for Older Adults SO JOURNAL OF THE AMERICAN MEDICAL DIRECTORS ASSOCIATION LA English DT Letter ID ELDERLY HOSPITALIZED-PATIENTS; GLOMERULAR-FILTRATION-RATE; ADVERSE DRUG-REACTIONS; PHARMACOKINETICS C1 [Hanlon, Joseph T.; Aspinall, Sherrie L.] Vet Affairs Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA USA. [Hanlon, Joseph T.] Pittsburgh VA Geriatr Res Educ & Clin Ctr, Pittsburgh, PA USA. [Hanlon, Joseph T.] Univ Pittsburgh, Sch Med Geriatr, Pittsburgh, PA USA. [Hanlon, Joseph T.; Aspinall, Sherrie L.] Univ Pittsburgh, Sch Pharm, Pittsburgh, PA USA. [Hanlon, Joseph T.; Aspinall, Sherrie L.] Univ Pittsburgh, Geriatr Pharmaceut & Gero Informat Res & Training, Pittsburgh, PA USA. [Hanlon, Joseph T.] Univ Pittsburgh, Sch Med, Dept Bioinformat, Pittsburgh, PA USA. [Hanlon, Joseph T.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA USA. [Aspinall, Sherrie L.] US Dept Vet Affairs, Pharm Benefits Management Serv, Hines, IL USA. RP Hanlon, JT (reprint author), Vet Affairs Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA USA. NR 8 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1525-8610 J9 J AM MED DIR ASSOC JI J. Am. Med. Dir. Assoc. PD JAN PY 2012 VL 13 IS 1 BP E6 EP E6 DI 10.1016/j.jamda.2011.06.014 PG 1 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA 898HT UT WOS:000300733100003 ER PT J AU Kelly, NA Mahoney, DF Bonner, A O'Malley, T AF Kelly, Nancy A. Mahoney, Diane F. Bonner, Alice O'Malley, Terrence TI Use of a Transitional Minimum Data Set (TMDS) to Improve Communication Between Nursing Home and Emergency Department Providers SO JOURNAL OF THE AMERICAN MEDICAL DIRECTORS ASSOCIATION LA English DT Article DE Transition of care; communication between providers; skilled nursing facility ID CARE; QUALITY; INFORMATION; TEAMWORK; OUTCOMES AB Objective: To study the adoption of a transitional minimum data set (TMDS) and its effectiveness in conveying essential clinical data elements between skilled nursing facility (SNF) and emergency department (ED) staff. Design: Retrospective medical record review of patients transferred from one SNF to one ED over a 14-month period before and after the implementation of the TMDS, to determine whether it improved data transfer compared with prior practice. Settings: One urban 140-bed SNF, averaging 17 ED transfers per month, and their affiliated ED at a major tertiary care hospital in Boston, MA. Participants: The medical records of 74 residents transferred from the SNF to the ED comprised the study data. Intervention: A Transition of Care Minimum Data Set necessary for ED care was developed based on a literature review and expert panel consensus. From this, a TMDS tool was derived. The nursing facility staff was trained on the use of the TMDS tool (Resident Transfer Form and transfer packet), which was sent with each patient at the time of transfer from the SNF to the ED. Measurements: Effectiveness of data transfer was determined by the proportion of TMDS items received by the ED following implementation of the TMDS in comparison with prior care. Adoption rate of the TMDS tool was determined by the proportion of hospital medical records that contained a paper copy of the resident transfer form. Results: Following the implementation of the TMDS there was statistically significant improvement in data transfer of 15 of 30 TMDS items. Among these items were the following: patient's family notified of transfer, contact information for the MD/NP at the SNF, contact information for obtaining more patient information from the SNF, resuscitation status, baseline cognitive and functional status, isolation precautions and risk alerts, and whether the SNF could accept the patient back after treatment in the ED. The Resident Transfer Form was found in the hospital medical record of 73% of patients. There were anecdotal reports of hospital provider satisfaction with the TMDS and RTF. Conclusion: The TMDS was associated with marked improvement in the transfer of essential clinical information. Educational efforts are warranted to increase consistency of usage. Copyright (C) 2012 - American Medical Directors Association, Inc. C1 [Kelly, Nancy A.] MGH Inst Hlth Profess, Sch Nursing, MGH Patient Care Serv, Boston, MA 02129 USA. [Bonner, Alice] Massachusetts Dept Publ Hlth, Boston, MA USA. [O'Malley, Terrence] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [O'Malley, Terrence] Partners Healthcare Syst Inc, Partners Continuing Care & Spaulding Rehabil Netw, Boston, MA USA. RP Kelly, NA (reprint author), MGH Inst Hlth Profess, Sch Nursing, MGH Patient Care Serv, Boston, MA 02129 USA. EM nkelly@mghihp.edu OI Mahoney, Diane/0000-0002-6415-475X NR 20 TC 1 Z9 1 U1 1 U2 14 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1525-8610 J9 J AM MED DIR ASSOC JI J. Am. Med. Dir. Assoc. PD JAN PY 2012 VL 13 IS 1 AR 85.e9 DI 10.1016/j.jamda.2011.02.007 PG 7 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA 898HT UT WOS:000300733100036 PM 21450258 ER PT J AU Shinagare, AB Ramaiya, NH Bellizzi, AM Mayer, RJ AF Shinagare, Atul B. Ramaiya, Nikhil H. Bellizzi, Andrew M. Mayer, Robert J. TI Locally advanced anaplastic pancreatic adenocarcinoma with initial response to FOLFIRINOX and rapid progression after five months SO PANCREATOLOGY LA English DT Article DE Anaplastic pancreatic carcinoma; FOLFIRINOX; CT; FDG-PET/CT ID UNDIFFERENTIATED CARCINOMA; PHASE-III; CANCER; CHEMOTHERAPY; GEMCITABINE; EXPRESSION AB Anaplastic pancreatic carcinoma (APC) is a rare, aggressive variant of pancreatic ductal adenocarcinoma. Surgery is the preferred treatment whenever possible, however APC is often unresectable at presentation and prognosis remains poor. We present a case of APC which showed a marked initial response to FOLFIRINOX with decreased size and increased cystic change, however then rapidly progressed with innumerable hepatic metastases after five months of FOLFIRINOX treatment. Although there is limited data on use of FOLFIRINOX in locally advanced pancreatic adenocarcinoma, it remains an attractive option in comparison to radiotherapy and 5-fluorouracil. Copyright (C) 2012, IAP and EPC. Published by Elsevier India, a division of Reed Elsevier India Pvt. Ltd. All rights reserved. C1 [Shinagare, Atul B.; Ramaiya, Nikhil H.] Dana Farber Canc Inst, Dept Imaging, Boston, MA 02215 USA. [Shinagare, Atul B.; Ramaiya, Nikhil H.] Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA. [Bellizzi, Andrew M.] Univ Iowa Hosp & Clin, Dept Pathol, Iowa City, IA 52242 USA. [Mayer, Robert J.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. [Mayer, Robert J.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. RP Shinagare, AB (reprint author), Dana Farber Canc Inst, Dept Imaging, 450 Brookline Ave, Boston, MA 02215 USA. EM ashinagare@partners.org NR 18 TC 0 Z9 0 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1424-3903 J9 PANCREATOLOGY JI Pancreatology PD JAN-FEB PY 2012 VL 12 IS 1 BP 35 EP 38 DI 10.1016/j.pan.2012.01.001 PG 4 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 902JZ UT WOS:000301035700006 PM 22487471 ER PT J AU Gudis, D Zhao, KQ Cohen, NA AF Gudis, David Zhao, Ke-qing Cohen, Noam A. TI Acquired cilia dysfunction in chronic rhinosinusitis SO AMERICAN JOURNAL OF RHINOLOGY & ALLERGY LA English DT Review ID CIGARETTE-SMOKE EXPOSURE; OUTER DYNEIN ARMS; SIGNAL-TRANSDUCTION MECHANISMS; MAMMALIAN RESPIRATORY-TRACT; BRONCHIAL EPITHELIAL-CELLS; SURFACE LIQUID VOLUME; BEAT FREQUENCY; CHRONIC SINUSITIS; MUCOCILIARY CLEARANCE; AIRWAY EPITHELIUM AB Background: Cilia are complex and powerful cellular structures of the respiratory mucosa that play a critical role in airway defense. Respiratory epithelium is lined with cilia that perform an integrated and coordinated mechanism called mucociliary clearance. Mucociliary clearance is the process by which cilia transport the mucus blanket overlying respiratory mucosa to the gastrointestinal tract for ingestion. It is the primary means by which the airway clears pathogens, allergens, debris, and toxins. The complex structure and regulatory mechanisms that dictate the form and function of normal cilia are not entirely understood, but it is clear that ciliary dysfunction results in impaired respiratory defense. Methods: A literature review of the current knowledge of cilia dysfunction in chronic rhinosinsusitis was conducted. Results: Ciliary dysfunction may be primary, the result of genetic mutations resulting in abnormal cilia structure, or, more commonly, secondary, the result of environmental, infectious, or inflammatory stimuli that disrupt normal motility or coordination. Patients with chronic rhinosinusitis (CRS) have been found to have impaired mucociliary clearance. Many biochemical, environmental, and mechanical stimuli have been shown to influence ciliary beat frequency, and common microbial pathogens of respiratory mucosa such as Pseudomonas aeruginosa and Haemophilus influenzae have developed toxins that appear to interrupt normal mucociliary function. Furthermore, inflammatory mediators known to be present in patients with CRS appear to impair secondarily mucociliary clearance. Conclusion: The goal of this article is to summarize the recent developments in the understanding of cilia dysfunction and mucociliary clearance in CRS. (Am J Rhinol Allergy 26, 1-6, 2012; doi: 10.2500/ajra.2012.26.3716) C1 [Gudis, David; Zhao, Ke-qing; Cohen, Noam A.] Univ Penn, Dept Otorhinolaryngol Head & Neck Surg, Philadelphia, PA 19104 USA. [Zhao, Ke-qing] Fudan Univ, Eye & Ear Nose & Throat Hosp, Dept Otorhinolaryngol Head & Neck Surg, Sch Shanghai Med, Shanghai 200433, Peoples R China. [Cohen, Noam A.] Philadelphia Vet Affairs Med Ctr, Div Otolaryngol, Philadelphia, PA USA. RP Cohen, NA (reprint author), Univ Penn, Dept Otorhinolaryngol Head & Neck Surg, Ravdin Bldg 5th Floor,3400 Spruce St, Philadelphia, PA 19104 USA. EM Noam.Cohen@uphs.upenn.edu OI Cohen, Noam/0000-0002-9462-3932 NR 92 TC 35 Z9 35 U1 0 U2 6 PU OCEAN SIDE PUBLICATIONS INC PI PROVIDENCE PA 95 PITMAN ST, PROVIDENCE, RI 02906 USA SN 1945-8924 J9 AM J RHINOL ALLERGY JI Am. J. Rhinol. Allergy PD JAN-FEB PY 2012 VL 26 IS 1 BP 1 EP 6 DI 10.2500/ajra.2012.26.3716 PG 6 WC Otorhinolaryngology SC Otorhinolaryngology GA 898VB UT WOS:000300769300012 PM 22391065 ER PT J AU Wise, SK Schlosser, RJ AF Wise, Sarah K. Schlosser, Rodney J. TI Subcutaneous and sublingual immunotherapy for allergic rhinitis: What is the evidence? SO AMERICAN JOURNAL OF RHINOLOGY & ALLERGY LA English DT Review ID RANDOMIZED CONTROLLED-TRIAL; HOUSE-DUST MITE; DOUBLE-BLIND; PEDIATRIC-PATIENTS; CLINICAL-EFFICACY; FATAL REACTIONS; POLLEN TABLET; DOUBLE-DUMMY; SAFETY; CHILDREN AB Background: Increasing interest in sublingual immunotherapy (SLIT) among practitioners and patients has resulted in numerous publications and clinical trials in recent years. With the clinical growth of SLIT, discussions of its efficacy, safety, and immunologic effects have intensified, as have comparisons to subcutaneous immunotherapy (SCIT). In the United States, SCIT has been the traditional form of immunotherapy for inhalant allergy and is the only immunotherapy method approved by the U. S. Food and Drug Administration at this time. The similarities and differences between SLIT and SCIT are often discussed, yet clinical studies directly comparing these immunotherapy methods are scarce. Methods: A literature review of specific issues and controversies between SLIT and SCIT for allergic rhinitis was conducted. Results: Safety, efficacy, and immunologic effects of these two immunotherapy techniques are reviewed. Conclusion: Unanswered questions relating to SLIT are examined. (Am J Rhinol Allergy 26, 18-22, 2012; doi: 10.2500/ajra.2012.26.3691) C1 [Schlosser, Rodney J.] Med Univ S Carolina, Dept Otolaryngol Head & Neck Surg, Charleston, SC 29425 USA. [Wise, Sarah K.] Emory Univ, Dept Otolaryngol Head & Neck Surg, Atlanta, GA 30322 USA. [Schlosser, Rodney J.] Med Univ S Carolina, Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC 29425 USA. RP Schlosser, RJ (reprint author), Med Univ S Carolina, Dept Otolaryngol Head & Neck Surg, 135 Rutledge Ave,MSC 550, Charleston, SC 29425 USA. EM schlossr@musc.edu NR 47 TC 11 Z9 15 U1 1 U2 8 PU OCEAN SIDE PUBLICATIONS INC PI PROVIDENCE PA 95 PITMAN ST, PROVIDENCE, RI 02906 USA SN 1945-8924 J9 AM J RHINOL ALLERGY JI Am. J. Rhinol. Allergy PD JAN-FEB PY 2012 VL 26 IS 1 BP 18 EP 22 DI 10.2500/ajra.2012.26.3691 PG 5 WC Otorhinolaryngology SC Otorhinolaryngology GA 898VB UT WOS:000300769300015 PM 22391071 ER PT J AU DeMaria, S Govindaraj, S Chinosorvatana, N Kang, S Levine, AI AF DeMaria, Samuel, Jr. Govindaraj, Satish Chinosorvatana, Nina Kang, Stanley Levine, Adam I. TI Bilateral sphenopalatine ganglion blockade improves postoperative analgesia after endoscopic sinus surgery SO AMERICAN JOURNAL OF RHINOLOGY & ALLERGY LA English DT Article ID INFRAORBITAL NERVE BLOCK; OUTPATIENT NASAL SURGERY; CLEFT-LIP REPAIR; AMBULATORY SURGERY; REGIONAL ANESTHESIA; PAIN; MANAGEMENT; DISCHARGE; HEADACHE; STAY AB Background: Endoscopic sinus surgery (ESS) is a common procedure preferably done with an anesthetic technique ensuring effective postoperative analgesia while speeding discharge home. Although anesthesia administered locally in conjunction with vasoconstricting agents is known to minimize intraoperative bleeding, its usefulness in providing postoperative analgesia has not been well characterized. The results supporting the use of regional anesthesia for sinus surgery have also been limited. Using a randomized, double-blinded and placebo-controlled design, we evaluated recovery times, opioid consumption, and nausea and vomiting after ESS when patients were randomized to either general anesthesia (GA) alone or with regional blockade. Methods: Subjects were 70 adults scheduled for sinus surgery. All participants underwent propofol/remifentanil/nitrous oxide anesthesia and similar intraoperative care. Patients received either GA alone or with sphenopalatine ganglion (SPG) blocks in a double-masked study design. Independent observers recorded readiness for discharge, incidence of nausea/vomiting, and pain scores every 15 minutes until discharge. Overall opioid use in the recovery area was also a secondary end point. Twenty-four hours later, patients were called and asked to rate their pain and overall satisfaction with their pain control. Results: Block group participants were considered ready for discharge after 45 minutes and discharged from the hospital similar to 40 minutes sooner than GA group participants. The block group required less total fentanyl in the recovery room than did the GA group. The incidences of nausea and vomiting did not differ significantly. Data at 24 hours postoperatively did not differ significantly between groups but trended toward increased satisfaction in the block group. No lasting adverse events were observed. Conclusion: Regional anesthesia using targeted nerve blocks is effective in ESS. The combination of GA and SPG blockade appears to shorten hospital stay and reduce narcotic requirements in the recovery area. No demonstrable benefits were observed after 24 hours regarding pain management. (Am J Rhinol Allergy 26, e23-e27, 2012; doi: 10.2500/ajra.2012.26.3709) C1 [DeMaria, Samuel, Jr.; Levine, Adam I.] Mt Sinai Med Ctr, Dept Anesthesiol, New York, NY 10029 USA. [Govindaraj, Satish; Chinosorvatana, Nina] Mt Sinai Med Ctr, Dept Otolaryngol, New York, NY 10029 USA. [Kang, Stanley] Massachusetts Gen Hosp, Dept Pain Management, Boston, MA 02114 USA. RP DeMaria, S (reprint author), Mt Sinai Med Ctr, Dept Anesthesiol, 1 Gustave L Levy Pl,Box 1010, New York, NY 10029 USA. EM samuel.demaria@mountsinai.org RI DeMaria, Samuel/I-8138-2013 OI DeMaria, Samuel/0000-0003-2808-5539 FU Department of Anesthesiology, Mount Sinai Medical Center FX Funded by the Department of Anesthesiology, Mount Sinai Medical Center NR 22 TC 4 Z9 5 U1 0 U2 2 PU OCEAN SIDE PUBLICATIONS INC PI PROVIDENCE PA 95 PITMAN ST, PROVIDENCE, RI 02906 USA SN 1945-8924 J9 AM J RHINOL ALLERGY JI Am. J. Rhinol. Allergy PD JAN-FEB PY 2012 VL 26 IS 1 BP E23 EP E27 DI 10.2500/ajra.2012.26.3709 PG 5 WC Otorhinolaryngology SC Otorhinolaryngology GA 898VB UT WOS:000300769300006 PM 22391074 ER PT S AU Milad, MR Quirk, GJ AF Milad, Mohammed R. Quirk, Gregory J. BE Fiske, ST Schacter, DL Taylor, SE TI Fear Extinction as a Model for Translational Neuroscience: Ten Years of Progress SO ANNUAL REVIEW OF PSYCHOLOGY, VOL 63 SE Annual Review of Psychology LA English DT Review; Book Chapter DE conditioning; prefrontal; cingulate; amygdala; fMRI; anxiety ID MEDIAL PREFRONTAL CORTEX; POSTTRAUMATIC-STRESS-DISORDER; POTENTIATED STARTLE PARADIGM; LONG-TERM POTENTIATION; INTERCALATED AMYGDALA NEURONS; COGNITIVE-BEHAVIORAL THERAPY; LOW-FREQUENCY STIMULATION; CEREBRAL-BLOOD-FLOW; CONDITIONED FEAR; FUNCTIONAL CONNECTIVITY AB The psychology of extinction has been studied for decades. Approximately 10 years ago, however, there began a concerted effort to understand the neural circuits of extinction of fear conditioning, in both animals and humans. Progress during this period has been facilitated by a high degree of coordination between rodent and human researchers examining fear extinction. Here we review the major advances and highlight new approaches to understanding and exploiting fear extinction. Research in fear extinction could serve as a model for translational research in other areas of behavioral neuroscience. C1 [Milad, Mohammed R.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Boston, MA 02129 USA. [Quirk, Gregory J.] Univ Puerto Rico, Sch Med, Dept Psychiat, San Juan, PR 00936 USA. [Quirk, Gregory J.] Univ Puerto Rico, Sch Med, Dept Anat & Neurobiol, San Juan, PR 00936 USA. RP Milad, MR (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Boston, MA 02129 USA. EM gjquirk@yahoo.com FU NIMH NIH HHS [P50 MH086400, K01 MH080346, K01-MH08036, P50-MH086400, R01 MH058883, R01 MH081975, R01-MH058883, R01-MH081975] NR 228 TC 338 Z9 343 U1 12 U2 99 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0897 USA SN 0066-4308 BN 978-0-8243-0263-4 J9 ANNU REV PSYCHOL JI Annu. Rev. Psychol PY 2012 VL 63 BP 129 EP 151 DI 10.1146/annurev.psych.121208.131631 PG 23 WC Psychology; Psychology, Multidisciplinary SC Psychology GA BYQ10 UT WOS:000299709900006 PM 22129456 ER PT J AU Echart, CL Somaini, S Distaso, M Palumbo, A Richardson, PG Fareed, J Iacobelli, M AF Echart, C. L. Somaini, S. Distaso, M. Palumbo, A. Richardson, P. G. Fareed, J. Iacobelli, M. TI Defibrotide Blunts the Prothrombotic Effect of Thalidomide on Endothelial Cells SO CLINICAL AND APPLIED THROMBOSIS-HEMOSTASIS LA English DT Article DE defibrotide; fibrinolysis; endothelium protection; multiple myeloma; antithrombotic ID HEPATIC VENOOCCLUSIVE DISEASE; MULTIPLE-MYELOMA; APOPTOSIS; TRANSPLANTATION; PREDNISONE; THROMBOSIS; MELPHALAN; TRIAL AB Patients with multiple myeloma (MM) are at relatively high risk of developing thromboembolic events such deep venous thrombosis (DVT) where thalidomide therapy has been identified to increase this risk. Defibrotide (DF), a polydisperse oligonucleotide, showed previously to counteract the alterations in endothelial cells (ECs) induced by lipopolysaccharide. It prompts us to investigate the impact of thalidomide on ECs and whether DF modulates changes in fibrinolysis induced by thalidomide. In this in vitro study, MM by itself alters the profibrinolytic potential of ECs decreasing the tissue plasminogen activator (t-PA) and increasing the plasminogen activator inhibitor 1 (PAI-1) levels which is potentiated by thalidomide. Defibrotide was able to counteract these effects. Additionally, DF upregulated the t-PA and downregulated PAI-1 gene expression modulated by thalidomide. Defibrotide also protects ECs from thalidomide-mediated cell death without interfering with its antitumor effects. These findings support DF clinical use for the prevention of DVT induced by immunomodulatory drugs. C1 [Echart, C. L.; Somaini, S.; Distaso, M.; Iacobelli, M.] Gentium SpA, Villa Guardia, Como, Italy. [Palumbo, A.] Univ Turin, Azienda Osped San Giovanni Battista, Div Ematol, Turin, Italy. [Richardson, P. G.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr, Boston, MA 02115 USA. [Fareed, J.] Loyola Univ, Med Ctr, Maywood, IL 60153 USA. RP Echart, CL (reprint author), Gentium SpA, Piazza 20,Settembre 2,2079 Villa Guardia Co, Villa Guardia, Como, Italy. EM cechart@gentium.it NR 26 TC 4 Z9 4 U1 2 U2 2 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1076-0296 J9 CLIN APPL THROMB-HEM JI Clin. Appl. Thromb.-Hemost. PD JAN-FEB PY 2012 VL 18 IS 1 BP 79 EP 86 DI 10.1177/1076029611412367 PG 8 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 893SX UT WOS:000300376800010 PM 21733935 ER PT J AU Stedman, MR Lew, RA Losina, E Gagnon, DR Solomon, DH Brookhart, MA AF Stedman, Margaret R. Lew, Robert A. Losina, Elena Gagnon, David R. Solomon, Daniel H. Brookhart, M. Alan TI A comparison of statistical approaches for physician-randomized trials with survival outcomes SO CONTEMPORARY CLINICAL TRIALS LA English DT Article DE Cluster randomized trials; Survival analysis; Physician-randomized trials; Permutation test; Simulation study; Shared frailty model ID OSTEOPOROSIS; IMPROVEMENT; PATIENT; TESTS; CARE AB This study compares methods for analyzing correlated survival data from physician-randomized trials of health care quality improvement interventions. Several proposed methods adjust for correlated survival data; however the most suitable method is unknown. Applying the characteristics of our study example, we performed three simulation studies to compare conditional, marginal, and non-parametric methods for analyzing clustered survival data. We simulated 1000 datasets using a shared frailty model with (1) fixed cluster size, (2) variable cluster size, and (3) non-lognormal random effects. Methods of analyses included: the nonlinear mixed model (conditional), the marginal proportional hazards model with robust standard errors, the clustered logrank test and the clustered permutation test (non-parametric). For each method considered we estimated Type I error, power, mean squared error, and the coverage probability of the treatment effect estimator. We observed underestimated Type I error for the clustered logrank test. The marginal proportional hazards method performed well even when model assumptions were violated. Nonlinear mixed models were only advantageous when the distribution was correctly specified. Published by Elsevier Inc. C1 [Stedman, Margaret R.; Losina, Elena] Brigham & Womens Hosp, Orthoped & Arthrit Ctr Outcomes Res, Dept Orthoped, Boston, MA 02115 USA. [Stedman, Margaret R.; Losina, Elena; Solomon, Daniel H.] Harvard Univ, Sch Med, Boston, MA USA. [Lew, Robert A.; Losina, Elena; Gagnon, David R.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. [Lew, Robert A.; Gagnon, David R.] Boston VA Healthcare Syst, MAVERIC, VA Cooperat Studies, Boston, MA USA. [Solomon, Daniel H.] Brigham & Womens Hosp, Div Rheumatol, Dept Med, Boston, MA 02115 USA. [Brookhart, M. Alan] Univ N Carolina, Dept Epidemiol, Gillings Sch Global Publ Hlth, Chapel Hill, NC USA. RP Stedman, MR (reprint author), Brigham & Womens Hosp, Orthoped & Arthrit Ctr Outcomes Res, Dept Orthoped, 75 Francis St,BC-4-4016, Boston, MA 02115 USA. EM mstedman2@partners.org OI Gagnon, David/0000-0002-6367-3179; Stedman, Margaret/0000-0001-9271-8332 FU National Institutes of Health [AG-027400, NRSA/T32 AR055885] FX The authors would like to thank Youyi Shu for her SAS program for simulating positive stable data and Sin-Ho Jung for his Fortran program for the logrank test. This work was supported in part by grants from the National Institutes of Health to Drs. Brookhart (AG-027400) and Stedman (NRSA/T32 AR055885). NR 27 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 1551-7144 J9 CONTEMP CLIN TRIALS JI Contemp. Clin. Trials PD JAN PY 2012 VL 33 IS 1 BP 104 EP 115 DI 10.1016/j.cct.2011.08.008 PG 12 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA 889KL UT WOS:000300072500018 PM 21924382 ER PT J AU Ruggiero, KJ Resnick, HS Paul, LA Gros, K McCauley, JL Acierno, R Morgan, M Galea, S AF Ruggiero, Kenneth J. Resnick, Heidi S. Paul, Lisa A. Gros, Kirstin McCauley, Jenna L. Acierno, Ron Morgan, Mark Galea, Sandro TI Randomized controlled trial of an internet-based intervention using random-digit-dial recruitment: the Disaster Recovery Web project SO CONTEMPORARY CLINICAL TRIALS LA English DT Article DE Disaster mental health; Internet intervention; Randomized controlled trial; Hurricane Ike; Posttraumatic stress ID POSTTRAUMATIC-STRESS-DISORDER; GENERALIZED ANXIETY DISORDER; STATE WORRY QUESTIONNAIRE; SEPTEMBER-11 TERRORIST ATTACKS; POST-RAPE PSYCHOPATHOLOGY; 2004 FLORIDA HURRICANES; NEW-YORK-CITY; IN-PERSON; PANIC DISORDER; MENTAL-HEALTH AB Disasters occur with high frequency throughout the world and increase risk for development of mental health problems in affected populations. Research focused on the development and evaluation of secondary prevention interventions addressing post-disaster mental health has high potential public-health impact. Toward this end, internet-based interventions (IBIS) are particularly attractive in that they: (1) offer a low-cost means of delivering standardized, targeted, personalized intervention content to a broad audience: and (2) are easily integrated within a stepped care approach to screening and service delivery. We describe a unique study design intended to evaluate an IBI with a disaster-affected population-based sample. Description and rationale are provided for sampling selection and procedures, selection of assessment measures and methods, design of the intervention, and statistical evaluation of critical outcomes. Unique features of this intervention include the use of a population-based sample, telephone and internet-based assessments, and development of a highly individualized web-based intervention. Challenges related to the development and large-scale evaluation of IBIs targeting post-disaster mental health problems, as well as implications for future research and practice are discussed. (C) 2011 Elsevier Inc. All rights reserved. C1 [Ruggiero, Kenneth J.; Resnick, Heidi S.; Paul, Lisa A.; Gros, Kirstin; McCauley, Jenna L.; Acierno, Ron] Med Univ S Carolina, Dept Psychiat & Behav Sci, Natl Crime Victims Res & Treatment Ctr, Charleston, SC 29425 USA. [Ruggiero, Kenneth J.; Acierno, Ron] Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC 29401 USA. [Morgan, Mark] Abt SRBI, New York, NY 10001 USA. [Galea, Sandro] Columbia Univ, Mailman Sch Publ Hlth, Dept Epidemiol, New York, NY 10032 USA. RP Ruggiero, KJ (reprint author), Med Univ S Carolina, Dept Psychiat & Behav Sci, Natl Crime Victims Res & Treatment Ctr, 67 President St,MSC861, Charleston, SC 29425 USA. EM ruggierk@musc.edu FU National Institute of Mental Health [R34 MH77149, R01 MH081056, P60 MH082598] FX This research was supported by National Institute of Mental Health Grants R34 MH77149 (PI: KJ Ruggiero), R01 MH081056 (PI: KJ Ruggiero), and P60 MH082598 (PI: FH Norris). All views and opinions expressed herein are those of the authors and do not necessarily reflect those of the funding agency or respective institutions. We acknowledge the important contributions of Wendy Muzzy and Kye Welsh of the Medical University of South Carolina, and of Daniel Loew of Abt SRBI. NR 87 TC 13 Z9 13 U1 7 U2 10 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1551-7144 J9 CONTEMP CLIN TRIALS JI Contemp. Clin. Trials PD JAN PY 2012 VL 33 IS 1 BP 237 EP 246 DI 10.1016/j.cct.2011.10.001 PG 10 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA 889KL UT WOS:000300072500034 PM 22008248 ER PT J AU Garcia, M Bruno, N Grunenwald, S Bui, E Birmes, P AF Garcia, Magalie Bruno, Nicolas Grunenwald, Solange Bui, Eric Birmes, Philippe TI Cortisol and post-traumatic stress disorder SO CORRESPONDANCES EN METABOLISMES HORMONES DIABETES ET NUTRITION LA French DT Article DE Cortisol; Post-traumatic stress disorder; Hypothalamic-pituitary-adrenal axis; Glucocorticoid receptor; FKPB5 gene AB Cortisol regulation abnormalities are noticed in post-traumatic stress disorder (PTSD). The basal cortisol level is often lowered. The reactivity of the hypothalamic-pituitary-adrenal (HPA) tests stimulation is increased. Exposure to a traumatic event may have more effects than PTSD itself on the HPA axis. At molecular level, some cartisol-related genes are more expressed in case of PTSD. In functional brain imaging, administration of glucocorticoids normalizes the abnormal activation of some areas previously modified by PTSD. Molecules targeting glucocorticoids receptors are used experimentally in animals, with encouraging results. C1 [Garcia, Magalie; Bui, Eric; Birmes, Philippe] Univ Toulouse 3, F-31062 Toulouse, France. [Garcia, Magalie; Bui, Eric; Birmes, Philippe] Hop Casselardit, Lab Stress Traumat LST EA 4560, Toulouse, France. [Bruno, Nicolas] CHU St Antoine, Psychiat Serv, Paris, France. [Grunenwald, Solange] CHU Toulouse, Serv Endocrinol Malad Metabol & Nutr, Toulouse, France. [Bui, Eric] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Bui, Eric] Harvard Univ, Sch Med, Boston, MA USA. RP Garcia, M (reprint author), Univ Toulouse 3, F-31062 Toulouse, France. RI Bui, Eric/J-8347-2015 OI Bui, Eric/0000-0002-1413-6473 NR 10 TC 0 Z9 0 U1 0 U2 5 PU EDIMARK SANTE PI COURBEVOIE CEDEX PA 2 RUE SAINTE-MARIE, COURBEVOIE CEDEX, 92418, FRANCE SN 2100-9619 J9 CORRESP MHDN JI Corresp. M H D N PD JAN-FEB PY 2012 VL 16 IS 1-2 BP 26 EP 30 PG 5 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 901YW UT WOS:000301006800006 ER PT J AU Larauche, M Mulak, A Tache, Y AF Larauche, Muriel Mulak, Agata Tache, Yvette TI Stress and visceral pain: From animal models to clinical therapies SO EXPERIMENTAL NEUROLOGY LA English DT Review DE Colorectal distension; CRF receptor; Irritable bowel syndrome; Mast cells; Stress; Visceral pain ID IRRITABLE-BOWEL-SYNDROME; CORTICOTROPIN-RELEASING-FACTOR; FUNCTIONAL GASTROINTESTINAL DISORDERS; NEONATAL MATERNAL SEPARATION; RECEPTOR-MEDIATED MECHANISMS; ANTERIOR CINGULATE CORTEX; LOCUS-COERULEUS NEURONS; CENTRAL-NERVOUS-SYSTEM; DSS-INDUCED COLITIS; ROBALZOTAN TARTRATE MONOHYDRATE AB Epidemiological studies have implicated stress (psychosocial and physical) as a trigger of first onset or exacerbation of irritable bowel syndrome (IBS) symptoms of which visceral pain is an integrant landmark. A number of experimental acute or chronic exteroceptive or interoceptive stressors induce visceral hyperalgesia in rodents although recent evidence also points to stress-related visceral analgesia as established in the somatic pain field. Underlying mechanisms of stress-related visceral hypersensitivity may involve a combination of sensitization of primary afferents, central sensitization in response to input from the viscera and dysregulation of descending pathways that modulate spinal nociceptive transmission or analgesic response. Biochemical coding of stress involves the recruitment of corticotropin releasing factor (CRF) signaling pathways. Experimental studies established that activation of brain and peripheral CRF receptor subtype 1 plays a primary role in the development of stress-related delayed visceral hyperalgesia while subtype 2 activation induces analgesic response. In line with stress pathways playing a role in IBS, nonpharmacologic and pharmacologic treatment modalities aimed at reducing stress perception using a broad range of evidence-based mind-body interventions and centrally-targeted medications to reduce anxiety impact on brain patterns activated by visceral stimuli and dampen visceral pain. (C) 2011 Elsevier Inc. All rights reserved. C1 [Larauche, Muriel] Univ Calif Los Angeles, CURE Digest Dis Res Ctr, W Los Angeles VA Med Ctr, Los Angeles, CA 90073 USA. [Larauche, Muriel; Mulak, Agata; Tache, Yvette] Univ Calif Los Angeles, Ctr Neurobiol Stress, Div Digest Dis, Dept Med,David Geffen Sch Med, Los Angeles, CA 90073 USA. [Larauche, Muriel; Tache, Yvette] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Mulak, Agata] Wroclaw Med Univ, Dept Gastroenterol & Hepatol, PL-50556 Wroclaw, Poland. RP Larauche, M (reprint author), Univ Calif Los Angeles, CURE Digest Dis Res Ctr, W Los Angeles VA Med Ctr, 11301 Wilshire Blvd,Bldg 115,Rm 111, Los Angeles, CA 90073 USA. EM mlarauche@mednet.ucla.edu OI Larauche, Muriel/0000-0003-3320-3675 FU NIH [R01 DK-57238, DK 33061, P50 DK-64539] FX This review is part of studies supported by the VA Research Career Scientist Award, NIH grants R01 DK-57238 and DK 33061 and P50 DK-64539 (YT). The authors thank Miss E. Hu for reviewing the manuscript. NR 368 TC 73 Z9 75 U1 4 U2 42 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 JAN PY 2012 VL 233 IS 1 BP 49 EP 67 DI 10.1016/j.expneurol.2011.04.020 PG 19 WC Neurosciences SC Neurosciences & Neurology GA 890CY UT WOS:000300123900007 PM 21575632 ER PT J AU Scherber, C Aranyosi, AJ Kulemann, B Thayer, SP Toner, M Iliopoulos, O Irimia, D AF Scherber, Cally Aranyosi, Alexander J. Kulemann, Birte Thayer, Sarah P. Toner, Mehmet Iliopoulos, Othon Irimia, Daniel TI Epithelial cell guidance by self-generated EGF gradients SO INTEGRATIVE BIOLOGY LA English DT Article ID EPIDERMAL-GROWTH-FACTOR; TYROSINE KINASE INHIBITOR; PERINEURAL INVASION; SUBMAXILLARY GLAND; TUMOR STROMA; CANCER-CELLS; MIGRATION; PROTEIN; INTERNALIZATION; FIBROBLASTS AB Cancer epithelial cells often migrate away from the primary tumor to invade into the surrounding tissues. Their migration is commonly assumed to be directed by pre-existent spatial gradients of chemokines and growth factors in the target tissues. Unexpectedly however, we found that the guided migration of epithelial cells is possible in vitro in the absence of pre-existent chemical gradients. We observed that both normal and cancer epithelial cells can migrate persistently and reach the exit along the shortest path from microscopic mazes filled with uniform concentrations of media. Using microscale engineering techniques and biophysical models, we uncovered a self-guidance strategy during which epithelial cells generate their own guiding cues under conditions of biochemical confinement. The self-guidance strategy depends on the balance between three interdependent processes: epidermal growth factor (EGF) uptake by the cells (U), the restricted transport of EGF through the structured microenvironment (T), and cell chemotaxis toward the resultant EGF gradients (C). The UTC self-guidance strategy can be perturbed by inhibition of signalling through EGF-receptors and appears to be independent from chemokine signalling. Better understanding of the UTC self-guidance strategy could eventually help devise new ways for modulating epithelial cell migration and delaying cancer cell invasion or accelerating wound healing. C1 [Scherber, Cally; Aranyosi, Alexander J.; Kulemann, Birte; Thayer, Sarah P.; Toner, Mehmet; Irimia, Daniel] Massachusetts Gen Hosp, Surg Serv, Boston, MA 02114 USA. [Scherber, Cally; Aranyosi, Alexander J.; Toner, Mehmet; Irimia, Daniel] Massachusetts Gen Hosp, BioMEMS Resource Ctr, Boston, MA 02114 USA. [Scherber, Cally; Aranyosi, Alexander J.; Kulemann, Birte; Thayer, Sarah P.; Toner, Mehmet; Irimia, Daniel] Harvard Univ, Sch Med, Boston, MA USA. [Iliopoulos, Othon] Massachusetts Gen Hosp, Ctr Canc Res, MGH Canc Ctr, Boston, MA 02114 USA. [Iliopoulos, Othon] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. RP Scherber, C (reprint author), Massachusetts Gen Hosp, Surg Serv, Boston, MA 02114 USA. EM dirimia@hms.harvard.edu OI Aranyosi, Alexander/0000-0002-8133-5026; Irimia, Daniel/0000-0001-7347-2082 FU National Institutes of Health [CA135601, EB002503, CA117969] FX We thank Dr Jun Yan for help with the biochemical analysis and Miss Nil Gural for help with the image analysis. This work was supported by funds from the National Institutes of Health (CA135601, EB002503, and CA117969). NR 37 TC 34 Z9 34 U1 0 U2 28 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 1757-9694 J9 INTEGR BIOL-UK JI Integr. Biol. PY 2012 VL 4 IS 3 BP 259 EP 269 DI 10.1039/c2ib00106c PG 11 WC Cell Biology SC Cell Biology GA 899PA UT WOS:000300827100002 PM 22314635 ER PT J AU Yerramilli-Rao, P Beal, MF Watanabe, D Kieburtz, K de Blieck, EA Kitano, M Hosoe, K Funahashi, I Cudkowicz, ME AF Yerramilli-Rao, Padmaja Beal, M. Flint Watanabe, Dai Kieburtz, Karl de Blieck, Elisabeth A. Kitano, Mitsuaki Hosoe, Kazunori Funahashi, Iwao Cudkowicz, Merit E. TI Oral Repeated-Dose Toxicity Studies of Coenzyme Q10 in Beagle Dogs SO INTERNATIONAL JOURNAL OF TOXICOLOGY LA English DT Article DE beagle dogs; coenzyme Q10; neurodegenerative disorders; toxicology; ubiquinone ID PLACEBO-CONTROLLED TRIAL; HUNTINGTONS-DISEASE; PARKINSONS-DISEASE; SAFETY ASSESSMENT; HEALTHY-SUBJECTS; DOUBLE-BLIND; Q(10); RATS; UBIQUINONE; REMACEMIDE AB To support phase III testing of coenzyme Q10 (CoQ(10)) in humans, we conducted pharmacokinetic and toxicology studies in beagle dogs. Following single gavage administration of CoQ(10) at 600, 1200, 1800, or 2400 mg/kg per d no obvious dose response was observed in maximum concentration (C-max) or area under the curve (AUC) versus time curve at the 3 highest dosages. In a repeated-dose study of CoQ(10) at 600, 1200, 1800, or 2400 mg/kg per d for 4 weeks, CoQ(10) reached steady state in plasma by 2 weeks at all dosages. Both C-max and AUC increased with increasing dosage of CoQ(10). The highest plasma levels were recorded at 1800 mg/kg per d. In a 39-week chronic toxicity study of CoQ(10) at 1200 and 1800 mg/kg per d or placebo, CoQ(10) reached steady state in plasma by 13 weeks. Behaviors, blood chemistries, and detailed histopathology were normal. No deaths occurred. These results support the use of a 2400 mg/d dosage of CoQ(10) in human clinical trials. C1 [Yerramilli-Rao, Padmaja; Cudkowicz, Merit E.] Harvard Univ, Sch Med, Dept Neurol, Neurol Clin Trials Unit,Massachusetts Gen Hosp, Boston, MA 02115 USA. [Beal, M. Flint] Cornell Univ, Dept Neurol, Weill Med Coll, New York, NY 10021 USA. [Beal, M. Flint] Cornell Univ, Dept Neurosci, Weill Med Coll, New York, NY 10021 USA. [Watanabe, Dai] Bozo Res Ctr Inc, Kannami Lab, Shizuoka, Japan. [Kieburtz, Karl; de Blieck, Elisabeth A.] Univ Rochester, Med Ctr, Ctr Human Expt Therapeut, Rochester, NY 14642 USA. [Kitano, Mitsuaki] Kaneka Corp, Pharmacol & Toxicol Lab, Frontier Biochem & Med Res Labs, Hyogo, Japan. [Hosoe, Kazunori; Funahashi, Iwao] Kaneka Corp, Sci Affairs & IP Grp, QOL Div, Osaka, Japan. RP Cudkowicz, ME (reprint author), Massachusetts Gen Hosp, Neurol Clin Trials Unit, 13th St,Bldg 149,Room 2274, Charlestown, MA 02129 USA. EM mcudkowicz@partners.org FU NINDS [5 R0I NS05292]; National Institutes of Health (NIH) [U0I NS050324]; Kaneka Corporation, Osaka, Japan FX This work was supported by Award Number 5 R0I NS05292 from the NINDS, Award Number U0I NS050324 from the National Institutes of Health (NIH), and Kaneka Corporation, Osaka, Japan. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NINDS or the NIH. The authors would like to thank Wendy Galpern for her review of the manuscript. NR 42 TC 1 Z9 4 U1 0 U2 6 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1091-5818 EI 1092-874X J9 INT J TOXICOL JI Int. J. Toxicol. PD JAN-FEB PY 2012 VL 31 IS 1 BP 58 EP 69 DI 10.1177/1091581811425256 PG 12 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 895PP UT WOS:000300508900007 PM 22267890 ER PT J AU Erickson, MA Niehoff, ML Farr, SA Morley, JE Dillman, LA Lynch, KM Banks, WA AF Erickson, Michelle A. Niehoff, Michael L. Farr, Susan A. Morley, John E. Dillman, Lucy A. Lynch, Kristin M. Banks, William A. TI Peripheral Administration of Antisense Oligonucleotides Targeting the Amyloid-beta Protein Precursor Reverses A beta PP and LRP-1 Overexpression in the Aged SAMP8 Mouse Brain SO JOURNAL OF ALZHEIMERS DISEASE LA English DT Article DE Abcb1; amyloid-beta peptides; amyloid-beta protein precursor; antisense; blood-brain barrier; LRP1; oligonucleotides; Pgp; RAGE; SAMP8 ID RECEPTOR-RELATED PROTEIN; SENESCENCE-ACCELERATED MOUSE; METHIONINE-ENKEPHALIN LEVELS; ALZHEIMERS-DISEASE; OBJECT RECOGNITION; CYTOPLASMIC DOMAIN; WATER MAZE; BARRIER; MEMORY; PEPTIDE AB The senescence accelerated mouse-prone 8 (SAMP8) mouse model of Alzheimer's disease has a natural mutation leading to age-related increases in the amyloid-beta protein precursor (A beta PP) and amyloid-beta (A beta) in the brain, memory impairment, and deficits in A beta removal from the brain. Previous studies show that centrally administered antisense oligonucleotide directed against A beta PP can decrease A beta PP expression and A beta production in the brains of aged SAMP8 mice, and improve memory. The same antisense crosses the blood-brain barrier and reverses memory deficits when injected intravenously. Here, we give 6 mu g of A beta PP or control antisense 3 times over 2 week intervals to 12 month old SAMP8 mice. Object recognition test was done 48 hours later, followed by removal of whole brains for immunoblot analysis of A beta PP, low-density lipoprotein-related protein-1 (LRP-1), p-glycoprotein (Pgp), receptor for advanced glycation endproducts (RAGE), or ELISA of soluble A beta(40). Our results show that A beta PP antisense completely reverses a 30% age-associated increase in A beta PP signal (p < 0.05 versus untreated 4 month old SAMP8). Soluble A beta(40) increased with age, but was not reversed by antisense. LRP-1 large and small subunits increased significantly with age (147.7%, p < 0.01 and 123.7%, p < 0.05 respectively), and A beta PP antisense completely reversed these increases (p < 0.05). Pgp and RAGE were not significantly altered with age or antisense. Antisense also caused improvements in memory (p < 0.001). Together, these data support the therapeutic potential of A beta PP antisense and show a unique association between A beta PP and LRP-1 expression in the SAMP8 mouse. C1 [Erickson, Michelle A.; Dillman, Lucy A.; Lynch, Kristin M.; Banks, William A.] Vet Affairs Puget Sound Hlth Care Syst, GRECC, Seattle, WA USA. [Erickson, Michelle A.; Dillman, Lucy A.; Lynch, Kristin M.; Banks, William A.] Univ Washington, Sch Med, Dept Internal Med, Div Gerontol & Geriatr Med, Seattle, WA USA. [Erickson, Michelle A.] St Louis Univ, Dept Physiol & Pharmacol, St Louis, MO 63103 USA. [Niehoff, Michael L.; Farr, Susan A.; Morley, John E.] Vet Affairs Med Ctr St Louis, St Louis, MO USA. [Niehoff, Michael L.; Farr, Susan A.; Morley, John E.] St Louis Univ, Sch Med, Dept Internal Med, Div Geriatr, St Louis, MO USA. RP Banks, WA (reprint author), Bldg 1,Rm 810A,1660 Columbian Way, Seattle, WA 98108 USA. EM bankswa@slu.edu FU VA Merit Review; National Institutes of Health [AG029839] FX This work was funded by VA Merit Review and the National Institutes of Health (AG029839). NR 64 TC 22 Z9 22 U1 3 U2 8 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 1387-2877 J9 J ALZHEIMERS DIS JI J. Alzheimers Dis. PY 2012 VL 28 IS 4 BP 951 EP 960 DI 10.3233/JAD-2011-111517 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 898DL UT WOS:000300715600019 PM 22179572 ER PT S AU Verdine, GL Hilinski, GJ AF Verdine, Gregory L. Hilinski, Gerard J. BE Wittrup, KD Verdine, GL TI STAPLED PEPTIDES FOR INTRACELLULAR DRUG TARGETS SO METHODS IN ENZYMOLOGY: PROTEIN ENGINEERING FOR THERAPEUTICS, VOL 203, PT B SE Methods in Enzymology LA English DT Review; Book Chapter ID PROTEIN-PROTEIN INTERACTIONS; CLOSING OLEFIN METATHESIS; STABILIZED ALPHA-HELICES; BH3 HELIX; ASYMMETRIC-SYNTHESIS; UNDRUGGABLE TARGETS; DRUGGABLE GENOME; NUCLEIC-ACIDS; BCL-2 DOMAINS; IN-VIVO AB Proteins that engage in intracellular interactions with other proteins are widely considered among the most biologically appealing yet chemically intractable targets for drug discovery. The critical interaction surfaces of these proteins typically lack the deep hydrophobic involutions that enable potent, selective targeting by small organic molecules, and their localization within the cell puts them beyond the reach of protein therapeutics. Considerable interest has therefore arisen in next-generation targeting molecules that combine the broad target recognition capabilities of protein therapeutics with the robust cell-penetrating ability of small molecules. One type that has shown promise in early-stage studies is hydrocarbon-stapled alpha-helical peptides, a novel class of synthetic miniproteins locked into their bioactive alpha-helical fold through the site-specific introduction of a chemical brace, an all-hydrocarbon staple. Stapling can greatly improve the pharmacologic performance of peptides, increasing their target affinity, proteolytic resistance, and serum half-life while conferring on them high levels of cell penetration through endocytic vesicle trafficking. Here, we discuss considerations crucial to the successful design and evaluation of potent stapled peptide interactions, our intention being to facilitate the broad application of this technology to intractable targets of both basic biologic interest and potential therapeutic value. C1 [Verdine, Gregory L.] Harvard Univ, Dept Chem & Chem Biol, Boston, MA 02115 USA. [Verdine, Gregory L.] Harvard Univ, Dept Stem Cell & Regenerat Biol, Boston, MA 02115 USA. [Verdine, Gregory L.] Harvard Univ, Dept Mol & Cellular Biol, Boston, MA 02115 USA. [Verdine, Gregory L.] Dana Farber Canc Inst, Program Canc Chem Biol, Boston, MA 02115 USA. [Hilinski, Gerard J.] Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA. RP Verdine, GL (reprint author), Harvard Univ, Dept Chem & Chem Biol, Boston, MA 02115 USA. NR 58 TC 148 Z9 151 U1 16 U2 145 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0076-6879 BN 978-0-12-396962-0 J9 METHOD ENZYMOL JI Methods Enzymol. PY 2012 VL 503 BP 3 EP 33 DI 10.1016/B978-0-12-396962-0.00001-X PG 31 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BYT78 UT WOS:000300198000001 PM 22230563 ER PT B AU Kim, DH Lee, JT AF Kim, Daniel H. Lee, Jeannie T. BE Morris, KV TI The X-chromosome Archetype for Non-coding RNA Regulation of the Epigenome SO NON-CODING RNAS AND EPIGENETIC REGULATION OF GENE EXPRESSION: DRIVERS OF NATURAL SELECTION LA English DT Article; Book Chapter ID EMBRYONIC STEM-CELLS; DOSAGE COMPENSATION; INACTIVATION CENTER; CHROMATIN-STRUCTURE; DNA METHYLATION; XIST GENE; TSIX; POLYCOMB; PLURIPOTENCY; COMPLEXES AB X-chromosome inactivation provides a model for discovering the still emerging functions of non-coding RNAs, which exhibit diverse roles in regulating the epigenome. Combining recent insights into X-chromosome non-coding RNAs with the advent of next-generation sequencing technologies promises many new discoveries in interrogating the functions of non-coding RNAs at the genomic level. Global RNA protein interaction information can now be queried by utilizing RNA immunoprecipitation followed by high-throughput sequencing (RIP-Seq), which has recently uncovered the diversity of the non-coding Polycomb transcriptome. In this chapter, we discuss non-coding RNAs of the X-inactivation centre that have provided unique insights into RNA molecules as molecular switches, guides and tethers to the epigenome, and key participants in diverse regulatory pathways, including RNA interference and Polycomb silencing. C1 [Kim, Daniel H.] CALTECH, Div Biol, Pasadena, CA 91125 USA. [Lee, Jeannie T.] Harvard Univ, Sch Med, Howard Hughes Med Inst, Dept Mol Biol,Massachusetts Gen Hosp,Dept Genet, Boston, MA 02115 USA. RP Kim, DH (reprint author), CALTECH, Div Biol, Pasadena, CA 91125 USA. EM dkim@caltech.edu; lee@molbio.mgh.harvard.edu NR 45 TC 0 Z9 0 U1 0 U2 0 PU CAISTER ACADEMIC PRESS PI WYMONDHAM PA 32 HEWITTS LANE, WYMONDHAM NR 18 0JA, ENGLAND BN 978-1-904455-94-3 PY 2012 BP 77 EP 83 PG 7 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Microbiology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Microbiology GA BYM54 UT WOS:000299358100004 ER PT J AU Daudi, A Cheng, ZY O'Brien, JA Mammarella, N Khan, S Ausubel, FM Bolwell, GP AF Daudi, Arsalan Cheng, Zhenyu O'Brien, Jose A. Mammarella, Nicole Khan, Safina Ausubel, Frederick M. Bolwell, G. Paul TI The Apoplastic Oxidative Burst Peroxidase in Arabidopsis Is a Major Component of Pattern-Triggered Immunity SO PLANT CELL LA English DT Article ID HYPERSENSITIVE CELL-DEATH; HYDROGEN-PEROXIDE; DEFENSE RESPONSE; PLANT DEFENSE; SUBCELLULAR-LOCALIZATION; MICROBE INTERACTIONS; OXIDASE GP91(PHOX); BASAL RESISTANCE; CROSS-LINKING; THALIANA AB In plants, reactive oxygen species (ROS) associated with the response to pathogen attack are generated by NADPH oxidases or apoplastic peroxidases. Antisense expression of a heterologous French bean (Phaseolus vulgaris) peroxidase (FBP1) cDNA in Arabidopsis thaliana was previously shown to diminish the expression of two Arabidopsis peroxidases (peroxidase 33 [PRX33] and PRX34), block the oxidative burst in response to a fungal elicitor, and cause enhanced susceptibility to a broad range of fungal and bacterial pathogens. Here we show that mature leaves of T-DNA insertion lines with diminished expression of PRX33 and PRX34 exhibit reduced ROS and callose deposition in response to microbe-associated molecular patterns (MAMPs), including the synthetic peptides Flg22 and Elf26 corresponding to bacterial flagellin and elongation factor Tu, respectively. PRX33 and PRX34 knockdown lines also exhibited diminished activation of Flg22-activated genes after Flg22 treatment. These MAMP-activated genes were also downregulated in unchallenged leaves of the peroxidase knockdown lines, suggesting that a low level of apoplastic ROS production may be required to preprime basal resistance. Finally, the PRX33 knockdown line is more susceptible to Pseudomonas syringae than wild-type plants. In aggregate, these data demonstrate that the peroxidase-dependent oxidative burst plays an important role in Arabidopsis basal resistance mediated by the recognition of MAMPs. C1 [Daudi, Arsalan; O'Brien, Jose A.; Khan, Safina; Bolwell, G. Paul] Univ London, Sch Biol Sci, Egham TW20 0EX, Surrey, England. [Cheng, Zhenyu; Mammarella, Nicole; Ausubel, Frederick M.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. [Cheng, Zhenyu; Mammarella, Nicole; Ausubel, Frederick M.] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. RP Bolwell, GP (reprint author), Univ London, Sch Biol Sci, Egham TW20 0EX, Surrey, England. EM p.bolwell@rhul.ac.uk FU National Science Foundation [MCB-0519898]; Natural Sciences and Engineering Research Council of Canada; National Institutes of Health [R37 GM48707]; Biotechnology and Biological Science Research Council [BB/E021166] FX We thank Annie Connery and Pauline Lim for carrying out the DAB quantitation using CellProfiler, Jenifer Bush for technical assistance, and Natalie Sykes for assistance with the DAB and callose staining. This work was supported by postdoctoral fellowships from the National Science Foundation (N.M.) and the Natural Sciences and Engineering Research Council of Canada (Z.C.), by National Institutes of Health grant R37 GM48707 and National Science Foundation grant MCB-0519898 (F.M.A.), and Biotechnology and Biological Science Research Council grant BB/E021166 (G.P.B). NR 47 TC 150 Z9 157 U1 5 U2 72 PU AMER SOC PLANT BIOLOGISTS PI ROCKVILLE PA 15501 MONONA DRIVE, ROCKVILLE, MD 20855 USA SN 1040-4651 J9 PLANT CELL JI Plant Cell PD JAN PY 2012 VL 24 IS 1 BP 275 EP 287 DI 10.1105/tpc.111.093039 PG 13 WC Biochemistry & Molecular Biology; Plant Sciences; Cell Biology SC Biochemistry & Molecular Biology; Plant Sciences; Cell Biology GA 900JA UT WOS:000300881800024 PM 22247251 ER PT J AU Hao, YS Hu, ZT Sieburth, D Kaplan, JM AF Hao, Yingsong Hu, Zhitao Sieburth, Derek Kaplan, Joshua M. TI RIC-7 Promotes Neuropeptide Secretion SO PLOS GENETICS LA English DT Article ID DENSE-CORE VESICLE; CAENORHABDITIS-ELEGANS; C-ELEGANS; NEUROTRANSMITTER RELEASE; NEUROMUSCULAR-JUNCTIONS; SYNAPTIC-TRANSMISSION; ACETYLCHOLINE-RELEASE; FUSION-COMPETENCE; MEMBRANE-FUSION; PLASMA-MEMBRANE AB Secretion of neurotransmitters and neuropeptides is mediated by exocytosis of distinct secretory organelles, synaptic vesicles (SVs) and dense core vesicles (DCVs) respectively. Relatively little is known about factors that differentially regulate SV and DCV secretion. Here we identify a novel protein RIC-7 that is required for neuropeptide secretion in Caenorhabditis elegans. The RIC-7 protein is expressed in all neurons and is localized to presynaptic terminals. Imaging, electrophysiology, and behavioral analysis of ric-7 mutants indicates that acetylcholine release occurs normally, while neuropeptide release is significantly decreased. These results suggest that RIC-7 promotes DCV-mediated secretion. C1 [Hao, Yingsong; Hu, Zhitao; Kaplan, Joshua M.] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. [Hao, Yingsong; Hu, Zhitao; Kaplan, Joshua M.] Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA 02115 USA. [Sieburth, Derek] Univ So Calif, Zilkha Neurogenet Inst, Los Angeles, CA USA. RP Hao, YS (reprint author), Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. EM kaplan@molbio.mgh.harvard.edu FU NIH [DK80215] FX This work was supported by NIH research grant DK80215 (JMK). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 47 TC 7 Z9 10 U1 2 U2 4 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1553-7390 J9 PLOS GENET JI PLoS Genet. PD JAN PY 2012 VL 8 IS 1 AR e1002464 DI 10.1371/journal.pgen.1002464 PG 12 WC Genetics & Heredity SC Genetics & Heredity GA 891NH UT WOS:000300223400028 PM 22275875 ER PT J AU Osorio, EY Zhao, WG Espitia, C Saldarriaga, O Hawel, L Byus, CV Travi, BL Melby, PC AF Osorio, E. Yaneth Zhao, Weiguo Espitia, Claudia Saldarriaga, Omar Hawel, Leo Byus, Craig V. Travi, Bruno L. Melby, Peter C. TI Progressive Visceral Leishmaniasis Is Driven by Dominant Parasite-induced STAT6 Activation and STAT6-dependent Host Arginase 1 Expression SO PLOS PATHOGENS LA English DT Article ID NITRIC-OXIDE SYNTHASE; MESSENGER-RNA EXPRESSION; T-CELL RESPONSES; INDIAN KALA-AZAR; CUTANEOUS LEISHMANIASIS; INTERFERON-GAMMA; IN-VIVO; ALTERNATIVE ACTIVATION; L-ARGININE; IFN-GAMMA AB The clinicopathological features of the hamster model of visceral leishmaniasis (VL) closely mimic active human disease. Studies in humans and hamsters indicate that the inability to control parasite replication in VL could be related to ineffective classical macrophage activation. Therefore, we hypothesized that the pathogenesis of VL might be driven by a program of alternative macrophage activation. Indeed, the infected hamster spleen showed low NOS2 but high arg1 enzyme activity and protein and mRNA expression (p < 0.001) and increased polyamine synthesis (p < 0.05). Increased arginase activity was also evident in macrophages isolated from the spleens of infected hamsters (p < 0.05), and arg1 expression was induced by L. donovani in primary hamster peritoneal macrophages (p < 0.001) and fibroblasts (p < 0.01), and in a hamster fibroblast cell line (p < 0.05), without synthesis of endogenous IL-4 or IL-13 or exposure to exogenous cytokines. miRNAi-mediated selective knockdown of hamster arginase 1 (arg1) in BHK cells led to increased generation of nitric oxide and reduced parasite burden (p < 0.005). Since many of the genes involved in alternative macrophage activation are regulated by Signal Transducer and Activator of Transcription-6 (STAT6), and because the parasite-induced expression of arg1 occurred in the absence of exogenous IL-4, we considered the possibility that L. donovani was directly activating STAT6. Indeed, exposure of hamster fibroblasts or macrophages to L. donovani resulted in dose-dependent STAT6 activation, even without the addition of exogenous cytokines. Knockdown of hamster STAT6 in BHK cells with miRNAi resulted in reduced arg1 mRNA expression and enhanced control of parasite replication (p < 0.0001). Collectively these data indicate that L. donovani infection induces macrophage STAT6 activation and STAT6-dependent arg1 expression, which do not require but are amplified by type 2 cytokines, and which contribute to impaired control of infection. C1 [Osorio, E. Yaneth; Zhao, Weiguo; Espitia, Claudia; Saldarriaga, Omar; Travi, Bruno L.; Melby, Peter C.] S Texas Vet Hlth Care Syst, Dept Vet Affairs Med Ctr, Res Serv, San Antonio, TX USA. [Osorio, E. Yaneth; Zhao, Weiguo; Espitia, Claudia; Travi, Bruno L.; Melby, Peter C.] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA. [Saldarriaga, Omar; Melby, Peter C.] Univ Texas Hlth Sci Ctr San Antonio, Dept Microbiol & Immunol, San Antonio, TX 78229 USA. [Hawel, Leo; Byus, Craig V.] Univ Calif Riverside, Div Biomed Sci, Riverside, CA 92521 USA. RP Osorio, EY (reprint author), Univ Texas Med Branch, Dept Internal Med, Ctr Trop Dis, Galveston, TX 77555 USA. EM melby@uthscsa.edu FU National Institutes of Allergy and Infectious Diseases, National Institutes of Health [AI061624]; Department of Veteran Affairs FX This work was supported by funding from the National Institutes of Allergy and Infectious Diseases, National Institutes of Health (AI061624) and the Department of Veteran Affairs. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 105 TC 22 Z9 24 U1 0 U2 6 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1553-7366 J9 PLOS PATHOG JI PLoS Pathog. PD JAN PY 2012 VL 8 IS 1 AR e1002417 DI 10.1371/journal.ppat.1002417 PG 17 WC Microbiology; Parasitology; Virology SC Microbiology; Parasitology; Virology GA 898UI UT WOS:000300767100007 PM 22275864 ER PT J AU Frissen, I Vroomen, J de Gelder, B AF Frissen, Ilja Vroomen, Jean de Gelder, Beatrice TI The Aftereffects of Ventriloquism: The Time Course of the Visual Recalibration of Auditory Localization SO SEEING AND PERCEIVING LA English DT Article DE Sensory perception; multisensory processes; perceptual adaptation; sound localization; ventriloquism after effect; time course ID SOUND LOCALIZATION; DIRECTED ATTENTION; ADAPTATION; FIELD; PLASTICITY; SYSTEMS; SPEECH; SPACE AB Exposure to synchronous but spatially discordant auditory and visual inputs produces adaptive recalibration of the respective localization processes, which manifest themselves in measurable aftereffects. Here we report two experiments that examined the time course of visual recalibration of apparent sound location in order to establish the build-up and dissipation of recalibration. In Experiment 1 participants performed a sound localization task before and during exposure to an auditory-visual discrepancy. In Experiment 2, participants performed a sound localization task before and after 60,180 or 300 exposures to the discrepancy and aftereffects were measured across a series of post-adaptation sound localization trials. The results show that recalibration is very fast. Substantial aftereffects are obtained after only 18-24 exposures and asymptote appears to be reached between 60 and 180 exposures. The rate of adaptation was independent of the size of the discrepancy. The retention of the aftereffect was strong, as we found no dissipation, not even after as few as 60 exposure trials. (C) Koninklijke Brill NV, Leiden, 2012 C1 [Frissen, Ilja; Vroomen, Jean] Tilburg Univ, Dept Med Psychol & Neuropsychol, NL-5000 LE Tilburg, Netherlands. [Frissen, Ilja] LUNAM Univ, Ecole Cent Nantes, Inst Rech Commun & Cybernet Nantes, Nantes, France. [de Gelder, Beatrice] Tilburg Univ, Cognit & Affect Neurosci Lab, NL-5000 LE Tilburg, Netherlands. [de Gelder, Beatrice] Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. RP Frissen, I (reprint author), Tilburg Univ, Dept Med Psychol & Neuropsychol, NL-5000 LE Tilburg, Netherlands. EM ilja.frissen@irccyn.ec-nantes.fr RI Vroomen, Jean/K-1033-2013 NR 37 TC 8 Z9 8 U1 1 U2 4 PU BRILL ACADEMIC PUBLISHERS PI LEIDEN PA PLANTIJNSTRAAT 2, P O BOX 9000, 2300 PA LEIDEN, NETHERLANDS SN 1878-4755 J9 SEEING PERCEIVING JI Seeing Perceiving PY 2012 VL 25 IS 1 BP 1 EP 14 DI 10.1163/187847611X620883 PG 14 WC Biophysics; Psychology; Psychology, Experimental SC Biophysics; Psychology GA 901JP UT WOS:000300963500001 PM 22353565 ER PT J AU Scalea, J Hanecamp, I Robson, SC Yamada, K AF Scalea, Joseph Hanecamp, Isabel Robson, Simon C. Yamada, Kazuhiko TI T-cell-mediated immunological barriers to xenotransplantation SO XENOTRANSPLANTATION LA English DT Review DE cellular responses; T cell; tolerance; xenotransplantation ID ISLET XENOGRAFT REJECTION; THYMIC LOBE TRANSPLANTATION; PLURIPOTENT STEM-CELLS; ANTI-PIG CYTOTOXICITY; SKIN-GRAFT TOLERANCE; GENE-KNOCKOUT PIGS; MINIATURE SWINE; ALPHA-1,3-GALACTOSYLTRANSFERASE GENE; BONE-MARROW; COMPOSITE THYMOKIDNEYS AB Xenotransplantion remains the most viable option for significant expansion of the donor organ pool in clinical transplantation. With the advent of nuclear transfer technologies, the production of transgenic swine has become a possibility. These animals have allowed transplant investigators to overcome humoral mechanisms of hyperacute xenograft rejection in experimental pig-to-non-human primate models. However, other immunologic barriers preclude long-term acceptance of xenografts. This review article focuses on a major feature of xenogeneic rejection: xenogeneic T cell responses. Evidence obtained from both small and large animal models, particularly those using either islet cells or kidneys, have demonstrated that T cell responses play a major role in xenogeneic rejection, and that immunosuppression alone is likely incapable of completely suppressing these responses. Additionally, both the direct and indirect pathway of antigen presentation appear to be involved in these anti donor processes. Enhanced understanding of ( i) CD47 and its role in transduced xeno-bone marrow ( ii) CD39 and its role in coagulation dysregulation and ( iii) thymic transplantation have provided us with encouraging results. Presently, experiments evaluating the possibility of xenogeneic tolerance are underway. C1 [Yamada, Kazuhiko] Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Organ Transplantat Tolerance & Xenotransplantat L, MGH E, Boston, MA 02129 USA. RP Yamada, K (reprint author), Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Organ Transplantat Tolerance & Xenotransplantat L, MGH E, Blg 14909019,13th St, Boston, MA 02129 USA. EM kaz.yamada@tbrc.mgh.harvard.edu FU NIAID NIH HHS [P01 AI045897] NR 84 TC 22 Z9 22 U1 0 U2 9 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0908-665X EI 1399-3089 J9 XENOTRANSPLANTATION JI Xenotransplantation PD JAN-FEB PY 2012 VL 19 IS 1 BP 23 EP 30 DI 10.1111/j.1399-3089.2011.00687.x PG 8 WC Medicine, Research & Experimental; Transplantation SC Research & Experimental Medicine; Transplantation GA 897ZT UT WOS:000300704100019 PM 22360750 ER PT J AU Sadhu, JM AF Sadhu, Julie M. TI Sexting: The Impact of a Cultural Phenomenon on Psychiatric Practice SO ACADEMIC PSYCHIATRY LA English DT Article C1 Mass Gen Hosp, Dept Psychiat, Boston, MA USA. RP Sadhu, JM (reprint author), Mass Gen Hosp, Dept Psychiat, Boston, MA USA. EM JSADHU@PARTNERS.ORG NR 17 TC 4 Z9 4 U1 0 U2 10 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 1042-9670 J9 ACAD PSYCHIATR JI Acad. Psych. PD JAN-FEB PY 2012 VL 36 IS 1 BP 76 EP 81 PG 6 WC Education & Educational Research; Psychiatry SC Education & Educational Research; Psychiatry GA 898PA UT WOS:000300753100020 PM 22362446 ER PT J AU Williams, EC Bryson, CL Sun, HL Chew, RB Chew, LD Blough, DK Au, DH Bradley, KA AF Williams, Emily C. Bryson, Chris L. Sun, Haili Chew, Ryan B. Chew, Lisa D. Blough, David K. Au, David H. Bradley, Katharine A. TI Association between Alcohol Screening Results and Hospitalizations for Trauma in Veterans Affairs Outpatients SO AMERICAN JOURNAL OF DRUG AND ALCOHOL ABUSE LA English DT Article DE alcohol screening; trauma; AUDIT-C; brief alcohol counseling intervention ID PRIMARY-CARE PATIENTS; PRIMARY-HEALTH-CARE; ALL-CAUSE MORTALITY; BRIEF INTERVENTION; PROBLEM DRINKING; CASE-CROSSOVER; SCORES; RISK; POPULATION; AUDIT AB Background: Alcohol consumption is a risk factor for traumatic injury, but it is unknown whether responses to alcohol screening questionnaires administered routinely in primary care are associated with subsequent hospitalization for traumatic injury. Objective: We evaluated the association between alcohol screening scores and the risk for subsequent hospitalizations for trauma among Veterans Affairs (VA) general medicine patients. Method: This study included VA outpatients (n = 32,623) at seven sites who returned mailed surveys (1997-1999). Alcohol Use Disorders Identification Test Consumption (AUDIT-C) scores grouped patients into six drinking categories representing nondrinkers, screen-negative drinkers, and drinkers who screened positive for mild, moderate, severe, and very severe alcohol misuse (scores 0, 1-3, 4-5, 6-7, 8-9, 10-12, respectively). VA administrative and Medicare data identified primary discharge diagnoses for trauma. Cox proportional hazard models were used to estimate the risk of trauma-related hospitalization for each drinking group adjusted for demographics, smoking, and comorbidity. Results: Compared with screen-negative drinkers, patients with severe and very severe alcohol misuse (AUDIT-C 8-9 and = 10) were at significantly increased risk for trauma-related hospitalization over the follow-up period (adjusted hazard ratios AUDIT-C: 8-9 2.06, 95% confidence interval (CI) 1.31-3.24 and AUDIT-C >= 10 2.13, 95% CI 1.32-3.42). Conclusions: Patients with severe and very severe alcohol misuse had a twofold increased risk of hospital admission for trauma compared to drinkers without alcohol misuse. Scientific Significance: Alcohol screening scores could be used to provide feedback to patients regarding risk of trauma-related hospitalization. Findings could be used by providers during brief alcohol-related interventions with patients with alcohol misuse. C1 [Williams, Emily C.; Bryson, Chris L.; Sun, Haili; Au, David H.; Bradley, Katharine A.] Vet Affairs VA Puget Sound Hlth Care Syst, Hlth Serv Res & Dev HSR& D NW Ctr Excellenc, Seattle, WA USA. [Williams, Emily C.; Bradley, Katharine A.] Univ Washington, Dept Hlth Sci, Seattle, WA 98195 USA. [Bryson, Chris L.; Chew, Lisa D.; Au, David H.; Bradley, Katharine A.] Univ Washington, Dept Med, Seattle, WA 98195 USA. [Chew, Ryan B.] Overlake Hosp, Med Ctr, Bellevue, WA USA. [Chew, Lisa D.] Univ Washington, Harborview Med Ctr, Adult Med Clin, Seattle, WA 98104 USA. [Blough, David K.] Univ Washington, Dept Pharm, Seattle, WA 98104 USA. RP Williams, EC (reprint author), VA Puget Sound Hlth Care Syst, Hlth Serv Res & Dev HSR& D NW Ctr Excellence, 1100 OliveWay,Suite 1400, Seattle, WA 98101 USA. EM emily.williams3@va.gov NR 37 TC 17 Z9 17 U1 1 U2 1 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 0095-2990 J9 AM J DRUG ALCOHOL AB JI Am. J. Drug Alcohol Abuse PD JAN PY 2012 VL 38 IS 1 BP 73 EP 80 DI 10.3109/00952990.2011.600392 PG 8 WC Psychology, Clinical; Substance Abuse SC Psychology; Substance Abuse GA 896HC UT WOS:000300555300011 PM 21797815 ER PT J AU Baffy, G AF Baffy, Gyoergy TI Hepatocellular Carcinoma in Type 2 Diabetes: More Than Meets the Eye SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Editorial Material ID FATTY LIVER-DISEASE; POPULATION-BASED COHORT; UNITED-STATES; RISK-FACTORS; CANCER; INFLAMMATION; MORTALITY; CIRRHOSIS; MELLITUS; OBESITY AB Hepatocellular carcinoma (HCC), a disease with poor survival rates unless recognized and treated early, ranks as the fifth most common cancer worldwide and has a rising incidence in the United States. Recent data indicate that the growing epidemic of type 2 diabetes mellitus may contribute to this alarming trend. In this issue, Lai et al. utilize a large Taiwanese insurance claims database to demonstrate that diabetes is associated with an increased risk of HCC. Moreover, this risk escalates if diabetes coincides with chronic hepatitis C and cirrhosis. Lai et al. also show that treatment with metformin or thiazolidinediones may reduce the risk of HCC. The findings may prompt risk stratification for HCC surveillance and improved disease control in diabetes as measures of cancer prevention. C1 [Baffy, Gyoergy] Harvard Univ, VA Boston Healthcare Syst, Gastroenterol Sect, Sch Med, Boston, MA 02130 USA. [Baffy, Gyoergy] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02130 USA. RP Baffy, G (reprint author), Harvard Univ, VA Boston Healthcare Syst, Gastroenterol Sect, Sch Med, 150 S Huntington Ave,Room 6A-46, Boston, MA 02130 USA. EM gbaffy@partners.org NR 25 TC 12 Z9 12 U1 1 U2 4 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0002-9270 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD JAN PY 2012 VL 107 IS 1 BP 53 EP 55 DI 10.1038/ajg.2011.390 PG 3 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 896NC UT WOS:000300573000009 PM 22218030 ER PT J AU Sterling, RK Wright, EC Morgan, TR Seeff, LB Hoefs, JC Di Bisceglie, AM Dienstag, JL Lok, AS AF Sterling, Richard K. Wright, Elizabeth C. Morgan, Timothy R. Seeff, Leonard B. Hoefs, John C. Di Bisceglie, Adrian M. Dienstag, Jules L. Lok, Anna S. CA HALT-C Trial Grp TI Frequency of Elevated Hepatocellular Carcinoma (HCC) Biomarkers in Patients With Advanced Hepatitis C SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Article ID GAMMA-CARBOXY PROTHROMBIN; SERUM ALPHA-FETOPROTEIN; UNITED-STATES; LIVER-DISEASE; RISK-FACTORS; DIAGNOSIS; CARBOXYPROTHROMBIN; SURVEILLANCE; SENSITIVITY; CIRRHOSIS AB OBJECTIVES: Prospective studies of serum hepatocellular carcinoma (HCC) biomarkers in patients with advanced hepatitis C are lacking. The aim of this study was to determine the frequencies and performance of elevated alpha-fetoprotein (AFP), AFP-L3, and des-gamma-carboxy prothrombin (DCP) levels as HCC biomarkers in advanced hepatitis C. METHODS: Patients in the HALT-C Trial were tested every 3 months for 42 months. Screening ultrasound was performed every 12 months. Levels of biomarkers were compared in patients in whom HCC did or did not develop. RESULTS: In all, 855 patients were evaluated; HCC developed in 46. Among patients without HCC, 73.2% had AFP consistently <20, 24.5% had at least one AFP between 20 and 199, and 2.3% had at least one AFP value >= 200 ng/ml; 73.7% had DCP consistently <90, 11.6% had at least one DCP between 90 and 149, and 14.7% had at least one DCP value >= 150 mAU/ml. AFP-L3 >= 10% was present at least once in 9.0% and in 17.1% of those with AFP >= 20 ng/ml. Among all patients with elevated biomarkers, a diagnosis of HCC was made in 0-31.6% (depending on the biomarker and cutoff) during the subsequent 24 months. AFP >= 200 ng/ml had the highest specificity (99%), but sensitivity was <= 20%. DCP >= 40 mAU/ml had the highest sensitivity (76%), but specificity was <= 58%. Independent predictors of elevated AFP were gender (female), race (Black), more advanced disease, and HCC. Elevated DCP was associated with more advanced disease and HCC. CONCLUSIONS: Mild-moderate elevations in total AFP and DCP but not in AFP-L3 occur frequently in patients with chronic hepatitis C and advanced fibrosis, are related to factors other than HCC, and are poor predictors of HCC. C1 [Sterling, Richard K.] Virginia Commonwealth Univ, Hepatol Sect, Med Ctr, Richmond, VA 23298 USA. [Wright, Elizabeth C.] NIDDK, Off Director, NIH, Dept Hlth & Human Serv, Bethesda, MD USA. [Morgan, Timothy R.; Hoefs, John C.] Univ Calif Irvine, Div Gastroenterol, Irvine, CA USA. [Morgan, Timothy R.] VA Long Beach Healthcare Syst, Gastroenterol Serv, Long Beach, CA USA. [Seeff, Leonard B.] NIDDK, Div Digest Dis & Nutr, NIH, Dept Hlth & Human Serv, Bethesda, MD USA. [Seeff, Leonard B.] NIDDK, Liver Dis Branch, NIH, Dept Hlth & Human Serv, Bethesda, MD USA. [Di Bisceglie, Adrian M.] St Louis Univ, Sch Med, Div Gastroenterol & Hepatol, St Louis, MO USA. [Dienstag, Jules L.] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. [Dienstag, Jules L.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Lok, Anna S.] Univ Michigan, Sch Med, Dept Internal Med, Div Gastroenterol, Ann Arbor, MI USA. RP Sterling, RK (reprint author), Virginia Commonwealth Univ, Hepatol Sect, Med Ctr, Med Coll Virginia Campus, Richmond, VA 23298 USA. EM RKSterli@vcu.edu OI Yang, Shuman/0000-0002-9638-0890 FU National Institute of Diabetes & Digestive & Kidney Diseases; National Institute of Allergy and Infectious Diseases (NIAID); National Cancer Institute; National Center for Minority Health and Health Disparities; General Clinical Research Center; Clinical and Translational Science Center from the National Center for Research Resources, National Institutes of Health FX This study was supported by the National Institute of Diabetes & Digestive & Kidney Diseases (contract numbers are listed below). Additional support was provided by the National Institute of Allergy and Infectious Diseases (NIAID), the National Cancer Institute, the National Center for Minority Health and Health Disparities, and by General Clinical Research Center and Clinical and Translational Science Center grants from the National Center for Research Resources, National Institutes of Health (grant numbers are listed below). Additional funding to conduct this study was supplied by Hoffmann-La Roche (now Genentech) and Wako Chemicals USA through Cooperative Research and Development Agreements (CRADAs) with the National Institutes of Health. NR 37 TC 36 Z9 37 U1 1 U2 11 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0002-9270 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD JAN PY 2012 VL 107 IS 1 BP 64 EP 74 DI 10.1038/ajg.2011.312 PG 11 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 896NC UT WOS:000300573000011 PM 21931376 ER PT J AU Post, JB Morin, KG Sano, M Jegede, AB Langhoff, E Spungen, AM AF Post, James B. Morin, Kel G. Sano, Mary Jegede, Adejoke B. Langhoff, Erik Spungen, Ann M. TI Increased Presence of Cognitive Impairment in Hemodialysis Patients in the Absence of Neurological Events SO AMERICAN JOURNAL OF NEPHROLOGY LA English DT Article DE Cognitive impairment; Chronic kidney disease; Hemodialysis ID CHRONIC KIDNEY-DISEASE; BRAIN; DEMENTIA; COHORT AB Background/Aims:Cognitive impairment (CI) is highly prevalent among hemodialysis (HD) patients and is associated with increased morbidity and mortality. The aim was to compare cognitive function in HD patients with no history of stroke or dementia and well-matched controls. Studies are required to determine the impact of HD and chronic kidney disease-specific risks on CI. Methods: 76 outpatients (50 receiving outpatient HD and 26 with normal kidney function matched for age and comorbidity) underwent a cross-sectional observational study. HD patients were well dialyzed and had optimal hemoglobin levels. A battery of eight neuropsychological tests was used. Outcomes included assessment scores of neurocognitive testing and prevalence and subtype of CI. Results: Compared to controls, HD subjects had significantly lower composite scores for each tested cognitive domain. In each domain except memory, the percentage of subjects with impairment was significantly higher in HD subjects than controls. Differences between the groups were independent of vascular and dementia risk factors. 82% of HD subjects met criteria for Cl versus 50% of controls. Non-amnestic subtype of Cl was more prevalent in both groups. Conclusion: Well-dialyzed HD patients with optimized hemoglobin levels and with no history of stroke or dementia performed significantly worse on multiple measures of cognition compared to controls. A higher prevalence of non-memory impairment may suggest an underlying vascular versus neurodegenerative mechanism. HD and chronic kidney disease-specific risk factors may contribute to early Cl not readily detected by routine screening methods. Copyright (C) 2011 S. Karger AG, Basel C1 [Post, James B.; Langhoff, Erik] James J Peters VA Med Ctr, Div Nephrol, Bronx, NY 10468 USA. [Post, James B.; Morin, Kel G.; Jegede, Adejoke B.; Spungen, Ann M.] James J Peters VA Med Ctr, VA RR&D Ctr Excellence Med Consequences SCI, Bronx, NY 10468 USA. [Sano, Mary] James J Peters VA Med Ctr, VA RR&D, Bronx, NY 10468 USA. [Post, James B.; Langhoff, Erik] Mt Sinai Sch Med, Dept Med, New York, NY USA. [Sano, Mary] Mt Sinai Sch Med, Dept Psychiat, New York, NY USA. RP Post, JB (reprint author), James J Peters VA Med Ctr, Div Nephrol, 130 W Kingsbridge Rd,4C-12 Outpatient Renal Pract, Bronx, NY 10468 USA. EM james.post@va.gov FU VA VISN; VA RRD CDA [B5050W]; VA RR&D Center of Excellence [B4162C]; NIH/NIA Alzheimer's Disease Research Center [AG005138] FX Funding for this project was provided by the VA VISN 3 Seed Grant Program, VA RR&D CDA 2 #B5050W, VA RR&D Center of Excellence #B4162C and NIH/NIA Alzheimer's Disease Research Center #AG005138. NR 24 TC 13 Z9 13 U1 1 U2 2 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0250-8095 J9 AM J NEPHROL JI Am. J. Nephrol. PY 2012 VL 35 IS 2 BP 120 EP 126 DI 10.1159/000334871 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA 896UY UT WOS:000300598100003 PM 22212437 ER PT J AU Appelbaum, FR Bacigalupo, A Soiffer, R AF Appelbaum, Frederick R. Bacigalupo, Andrea Soiffer, Robert TI Anti-T Cell Antibodies as Part of the Preparative Regimen in Hematopoietic Cell Transplantation-A Debate SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article ID VERSUS-HOST-DISEASE; MATCHED UNRELATED DONORS; ANTITHYMOCYTE GLOBULIN; RANDOMIZED-TRIAL; ACUTE GRAFT; PROPHYLAXIS; PREVENTION; DEPLETION; RISK C1 [Appelbaum, Frederick R.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98109 USA. [Bacigalupo, Andrea] S Martinos Hosp, Genoa, Italy. [Soiffer, Robert] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Appelbaum, FR (reprint author), Fred Hutchinson Canc Res Ctr, 1100 Fairview Ave N,D5-310, Seattle, WA 98109 USA. FU Fresenius; Genzyme FX Dr. Bacigalupo has received small consulting fees from Fresenius and Genzyme. The authors have nothing to disclose. NR 15 TC 8 Z9 8 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD JAN PY 2012 VL 18 IS 1 SU 1 BP S111 EP S115 DI 10.1016/j.bbmt.2011.11.002 PG 5 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 878EY UT WOS:000299239500021 PM 22226093 ER PT J AU Chapman, M Warren, EH Wu, CJ AF Chapman, Michael Warren, Edus H., III Wu, Catherine J. TI Applications of Next-Generation Sequencing to Blood and Marrow Transplantation SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article DE Genome analysis; Exome sequencing; Transplantation; TCR ID ACUTE MYELOID-LEUKEMIA; STEM-CELL TRANSPLANTATION; MULTIPLE-MYELOMA; GAMMA-DELTA; T-CELLS; TUMOR-REGRESSION; ALPHA-BETA; B-CELL; MUTATIONS; GENOME AB Since the advent of next-generation sequencing (NGS) in 2005, there has been an explosion of published studies employing the technology to tackle previously intractable questions in many disparate biological fields. This has been coupled with technology development that has occurred at a remarkable pace. This review discusses the potential impact of this new technology on the field of blood and marrow stem cell transplantation. Hematologic malignancies have been among the forefront of those cancers whose genomes have been the subject of NGS. Hence, these studies have opened novel areas of biology that can be exploited for prognostic, diagnostic, and therapeutic means. Because of the unprecedented depth, resolution and accuracy achievable by NGS, this technology is well-suited for providing detailed information on the diversity of receptors that govern antigen recognition; this approach has the potential to contribute important insights into understanding the biologic effects of transplantation. Finally, the ability to perform comprehensive tumor sequencing provides a systematic approach to the discovery of genetic alterations that can encode peptides with restricted tumor expression, and hence serve as potential target antigens of graft-versus-leukemia responses. Altogether, this increasingly affordable technology will undoubtedly impact the future practice and care of patients with hematologic malignancies. Biol Blood Marrow Transplant 18: S151-S160 (2012) (C) 2012 American Society for Blood and Marrow Transplantation C1 [Wu, Catherine J.] Harvard Inst Med, Dana Farber Canc Inst, Canc Vaccine Ctr, Boston, MA 02115 USA. [Chapman, Michael] Univ Cambridge, Dept Haematol, Cambridge, England. [Warren, Edus H., III] Fred Hutchinson Canc Res Ctr, Program Immunol, Seattle, WA 98104 USA. RP Wu, CJ (reprint author), Harvard Inst Med, Dana Farber Canc Inst, Canc Vaccine Ctr, Rm 416B,77 Ave Louis Pasteur, Boston, MA 02115 USA. EM cwu@partners.org OI Warren, Edus/0000-0002-9570-2755 FU Leukaemia and Lymphoma Research; Clinical Scientist Award in Translational Research from the Burroughs Wellcome Fund [1007475]; NIH [P30 CA015704-37, R43 DK089783, R56 AI081860, NCI-1R01CA155010-01A1]; Damon-Runyon Cancer Research Foundation [CI-38-07]; Leukemia and Lymphoma Society; Blavatnik Family Foundation FX M.C. acknowledges support from Leukaemia and Lymphoma Research. E.H.W. is supported by a Clinical Scientist Award in Translational Research from the Burroughs Wellcome Fund (1007475) and NIH Grants P30 CA015704-37, R43 DK089783, and R56 AI081860. C.J.W is supported by a Clinical Investigator award from the Damon-Runyon Cancer Research Foundation (CI-38-07) and acknowledges support from the Leukemia and Lymphoma Society Translational Research Program, the Blavatnik Family Foundation, and from the NIH (NCI-1R01CA155010-01A1). NR 47 TC 8 Z9 8 U1 0 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD JAN PY 2012 VL 18 IS 1 SU 1 BP S151 EP S160 DI 10.1016/j.bbmt.2011.11.011 PG 10 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 878EY UT WOS:000299239500026 PM 22226099 ER PT J AU Confer, DL Weisdorf, D Weinstock, D Case, C Chao, N AF Confer, Dennis L. Weisdorf, Daniel Weinstock, David Case, Cullen Chao, Nelson TI Radiation Disasters: Role of the BMT Team SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article ID NUCLEAR DETONATION; SCARCE RESOURCES; ALLOCATION; STANDARDS; TRIAGE AB Bone marrow transplant (BMT) teams do not generally consider themselves to be emergency responders. But the bone marrow is the most radiosensitive organ in the body, and early changes in peripheral blood counts remain the best indicator of major total-body radiation exposures. Following a mass casualty incident, such as that occasioned by a nuclear detonation, BMT teams should expect that they will be called upon for their expertise in managing severe myelosuppression. Numerous resources, including the Radiation Injury Treatment Network, are available to assist BMT teams in planning for such a role. Biol Blood Marrow Transplant 18: S189-S192 (2012) (C) 2012 Published by Elsevier Inc. on behalf of American Society for Blood and Marrow Transplantation C1 [Confer, Dennis L.; Case, Cullen] Natl Marrow Donor Program, Minneapolis, MN 55447 USA. [Weisdorf, Daniel] Univ Minnesota, Masonic Canc Ctr, Minneapolis, MN USA. [Weinstock, David] Dana Farber Canc Inst, Boston, MA 02115 USA. [Chao, Nelson] Duke Univ, Med Ctr, Durham, NC USA. RP Confer, DL (reprint author), Natl Marrow Donor Program, 3001 Broadway St NE,Suite 100, Minneapolis, MN 55447 USA. EM dconfer@nmdp.org NR 12 TC 1 Z9 2 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD JAN PY 2012 VL 18 IS 1 SU 1 BP S189 EP S192 DI 10.1016/j.bbmt.2011.11.021 PG 4 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 878EY UT WOS:000299239500032 PM 22226106 ER PT J AU Matsui, W Borrello, I Mitsiades, C AF Matsui, William Borrello, Ivan Mitsiades, Constantine TI Autologous Stem Cell Transplantation and Multiple Myeloma Cancer Stem Cells SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article ID HIGH-DOSE THERAPY; PERIPHERAL-BLOOD; RANDOMIZED-TRIAL; BONE-MARROW; B-CELLS; STANDARD CHEMOTHERAPY; MAINTENANCE TREATMENT; IMPROVES SURVIVAL; PLASMA-CELLS; IN-VIVO AB It is well established that high-dose therapy (HDT) combined with autologous stem cell transplantation (ASCT) produces superior response rates and progression-free survival compared with conventional chemotherapy in patients with multiple myeloma (MM). Accordingly, MM currently represents the most common indication for ASCT. Despite these clinical improvements, the impact of ASCT on overall survival is unclear because the vast majority of patients eventually experience disease relapse and progression. The continual risk of relapse suggests that malignant cells resistant to HDT possess the clonogenic growth potential to mediate tumor regrowth, and in several diseases cancer stem cells (CSCs) have been identified that are both highly tumorigenic and resistant to standard anticancer approaches. Putative CSCs have been identified in MM, and their characterization may lead to the development of novel maintenance strategies that inhibit the production of new tumor cells, prevent disease relapse, and improve overall survival. Biol Blood Marrow Transplant 18: S27-S32 (2012) (C) 2012 American Society for Blood and Marrow Transplantation C1 [Matsui, William; Borrello, Ivan] Johns Hopkins Univ, Sidney Kimmel Comprehens Canc Ctr, Sch Med, Div Hematol Malignancies,Dept Oncol, Baltimore, MD 21287 USA. [Mitsiades, Constantine] Harvard Univ, Sch Med, Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr,Dept Med Oncol, Boston, MA 02115 USA. RP Matsui, W (reprint author), Johns Hopkins Univ, Sidney Kimmel Comprehens Canc Ctr, Sch Med, Div Hematol Malignancies,Dept Oncol, CRB245,1650 Orleans St, Baltimore, MD 21287 USA. EM matsuwi@jhmi.edu OI Matsui, William/0000-0002-3088-0964 FU NCI NIH HHS [R01 CA127574-03, R01 CA127574, R01 CA127574-01A2, R01 CA127574-02, R01 CA127574-02S1, R01 CA127574-04, R21 CA155733, R21 CA155733-01A1, R21 CA155733-02] NR 48 TC 14 Z9 14 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD JAN PY 2012 VL 18 IS 1 SU 1 BP S27 EP S32 DI 10.1016/j.bbmt.2011.10.036 PG 6 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 878EY UT WOS:000299239500010 PM 22226109 ER PT J AU Reddy, P de Lima, M Koreth, J AF Reddy, Pavan de Lima, Marcos Koreth, John TI Emerging Therapies in Hematopoietic Stem Cell Transplantation SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article DE Allogeneic; Proteasome; Bortezomib; HDAC; Hypomethylating agent; Azacytidine; Review ID VERSUS-HOST-DISEASE; SUBEROYLANILIDE HYDROXAMIC ACID; PROTEASOME INHIBITOR BORTEZOMIB; NF-KAPPA-B; HISTONE DEACETYLASE INHIBITORS; DENDRITIC CELLS; TUMOR-CELLS; MULTIPLE-MYELOMA; IMMUNE-RESPONSES; IN-VITRO AB Despite improvements to hematopoietic stem cell transplantation over the past several decades, further advances are necessary to achieve: improved control of toxicities like graft-versus-host disease; enhanced immunologic reconstitution posttransplantation; and reduction in relapse risk via enhancement of graft-versus-tumor responses. Achieving these disparate hematopoietic stem cell transplantation goals will likely require the introduction of novel therapeutic agents to the current armamentarium. In this article, we outline preclinical and early-phase clinical data indicating the potential of proteasome-inhibitor therapy (bortezomib), hypomethylating agent therapy (azacytidine), and histone deacetylase-inhibitor therapy (vorinostat) to help improve hematopoietic stem cell transplantation outcomes. Biol Blood Marrow Transplant 18: S125-S131 (2012) (C) 2012 American Society for Blood and Marrow Transplantation C1 [Koreth, John] Dana Farber Canc Inst, Div Hematol Malignancies, Boston, MA 02215 USA. [Reddy, Pavan] Univ Michigan, Ann Arbor, MI 48109 USA. [de Lima, Marcos] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. RP Koreth, J (reprint author), Dana Farber Canc Inst, Div Hematol Malignancies, 450 Brookline Ave, Boston, MA 02215 USA. EM john_koreth@dfci.harvard.edu FU Merck; Celgene FX Merck has contributed drugs and financing for the clinical trial. Dr. de Lima received a research grant from Celgene. NR 59 TC 5 Z9 5 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD JAN PY 2012 VL 18 IS 1 SU 1 BP S125 EP S131 DI 10.1016/j.bbmt.2011.10.022 PG 7 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 878EY UT WOS:000299239500023 PM 22226096 ER PT J AU Reddy, P Socie, G Cutler, C Weisdorf, D AF Reddy, Pavan Socie, Gerard Cutler, Corey Weisdorf, Daniel TI GVHD Prevention: An Ounce Is Better Than a Pound SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Editorial Material ID VERSUS-HOST-DISEASE; BONE-MARROW-TRANSPLANTATION; REGULATORY T-CELLS; TOTAL-BODY IRRADIATION; CLASS-II-DISPARATE; GRAFT-REJECTION; TUMOR ACTIVITY; DONOR; TH2; LEUKEMIA C1 [Reddy, Pavan] Univ Michigan, Dept Med CCGC 3312, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA. [Socie, Gerard] Hop St Louis, AP HP, Serv Hematol Greffe de Moelle, Paris, France. [Socie, Gerard] Univ Paris 07, Paris, France. [Socie, Gerard] Unite INSERM U728, Paris, France. [Cutler, Corey] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Weisdorf, Daniel] Mason Canc Ctr, Div Hematol, Minneapolis, MN USA. RP Reddy, P (reprint author), Univ Michigan, Dept Med CCGC 3312, Ctr Comprehens Canc, 1500 E Med Ctr Dr, Ann Arbor, MI 48109 USA. EM reddypr@umich.edu FU NCI NIH HHS [R01 CA143379, R01 CA143379-03]; NHLBI NIH HHS [HL-090775, R01 HL090775, R01 HL090775-05]; NIAID NIH HHS [AI-075284, R01 AI075284, R01 AI075284-05] NR 64 TC 4 Z9 4 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 EI 1523-6536 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD JAN PY 2012 VL 18 IS 1 SU 1 BP S17 EP S21 DI 10.1016/j.bbmt.2011.10.034 PG 5 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 878EY UT WOS:000299239500007 PM 22226102 ER PT J AU Abuabara, K Lee, H Kimball, AB AF Abuabara, K. Lee, H. Kimball, A. B. TI Association of systemic psoriasis therapies and incidence of myocardial infarction: reply from authors SO BRITISH JOURNAL OF DERMATOLOGY LA English DT Letter C1 [Kimball, A. B.] Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA. [Abuabara, K.] Univ Penn, Dept Dermatol, Philadelphia, PA 19104 USA. [Lee, H.] Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA. RP Kimball, AB (reprint author), Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA. EM harvardskinstudies@partners.org NR 2 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0007-0963 J9 BRIT J DERMATOL JI Br. J. Dermatol. PD JAN PY 2012 VL 166 IS 1 BP 233 EP 233 DI 10.1111/j.1365-2133.2011.10668.x PG 1 WC Dermatology SC Dermatology GA 897XU UT WOS:000300695900072 PM 21966952 ER PT J AU Becker, AE Kleinman, A AF Becker, Anne E. Kleinman, Arthur TI An Agenda for Closing Resource Gaps in Global Mental Health: Innovation, Capacity Building, and Partnerships Introduction SO HARVARD REVIEW OF PSYCHIATRY LA English DT Editorial Material C1 [Becker, Anne E.; Kleinman, Arthur] Harvard Univ, Sch Med, Dept Global Hlth & Social Med, Boston, MA 02115 USA. [Becker, Anne E.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Kleinman, Arthur] Harvard Univ, Asia Ctr, Boston, MA 02115 USA. Harvard Univ, Dept Anthropol, Boston, MA 02115 USA. RP Becker, AE (reprint author), Harvard Univ, Sch Med, Dept Global Hlth & Social Med, Boston, MA 02115 USA. EM anne_becker@hms.harvard.edu; kleinman@wjh.harvard.edu NR 5 TC 5 Z9 5 U1 1 U2 4 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1067-3229 J9 HARVARD REV PSYCHIAT JI Harv. Rev. Psychiatr. PD JAN-FEB PY 2012 VL 20 IS 1 BP 3 EP 5 DI 10.3109/10673229.2012.652875 PG 3 WC Psychiatry SC Psychiatry GA 895IO UT WOS:000300489900002 PM 22335177 ER PT J AU Fricchione, GL Borba, CPC Alem, A Shibre, T Carney, JR Henderson, DC AF Fricchione, Gregory L. Borba, Christina P. C. Alem, Atalay Shibre, Teshome Carney, Julia R. Henderson, David C. TI Capacity Building in Global Mental Health: Professional Training SO HARVARD REVIEW OF PSYCHIATRY LA English DT Review DE capacity building; global mental health; psychiatry education ID RANDOMIZED CONTROLLED-TRIAL; COST-EFFECTIVENESS; LOW-INCOME; DEPRESSION; CARE; WORLD; PSYCHIATRY; DISORDERS; RESOURCES; COUNTRIES AB We suggest that the optimal approach to building capacity in global mental health care will require partnerships between professional resources in high-income countries and promising health-related institutions in low-and middle-income countries. The result of these partnerships will be sustainable academic relationships that can educate a new generation of in-country primary care physicians and, eventually, specialized health professionals. Research capabilities will be an essential educational component to inform policy and practice, and to ensure careful outcome measurements of training and of intervention, prevention, and promotion strategies. The goal of these academic centers of excellence will be to develop quality, in-country clinical and research professionals, and to build a productive environment for these professionals to advance their careers locally. In sum, this article discusses human capacity building in global mental health, provides recommendations for training, and offers examples of recent initiatives. (HARV REV PSYCHIATRY 2012; 20: 47-57.) C1 [Fricchione, Gregory L.; Borba, Christina P. C.; Carney, Julia R.; Henderson, David C.] Massachusetts Gen Hosp, Dept Psychiat, Pierce Global Div, Boston, MA 02114 USA. [Fricchione, Gregory L.; Borba, Christina P. C.; Carney, Julia R.; Henderson, David C.] Harvard Univ, Sch Med, Boston, MA USA. [Alem, Atalay; Shibre, Teshome] Univ Addis Ababa, Dept Psychiat, Addis Ababa, Ethiopia. RP Fricchione, GL (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Pierce Global Div, 55 Fruit St, Boston, MA 02114 USA. EM gfricchione@partners.org RI yan, liu/A-1822-2015 OI yan, liu/0000-0001-8517-1084 NR 37 TC 18 Z9 18 U1 0 U2 9 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1067-3229 J9 HARVARD REV PSYCHIAT JI Harv. Rev. Psychiatr. PD JAN-FEB PY 2012 VL 20 IS 1 BP 47 EP 57 DI 10.3109/10673229.2012.655211 PG 11 WC Psychiatry SC Psychiatry GA 895IO UT WOS:000300489900007 PM 22335182 ER PT J AU Hooper, DG Bolton, VE Sutton, JS Guilford, FT Straus, DC Najvar, LK Wiederhold, NP Kirkpatrick, WR Patterson, TF AF Hooper, Dennis G. Bolton, Vincent E. Sutton, John S. Guilford, Frederick T. Straus, David C. Najvar, Laura K. Wiederhold, Nathan P. Kirkpatrick, William R. Patterson, Thomas F. TI Assessment of Aspergillus fumigatus in Guinea Pig Bronchoalveolar Lavages and Pulmonary Tissue by Culture and Realtime Polymerase Chain Reaction Studies SO INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES LA English DT Article DE Aspergillus fumigatus; Realtime PCR; bronchoalveolar lavages ID INVASIVE ASPERGILLOSIS; TRANSPLANT RECIPIENTS; QUANTITATIVE PCR; GALACTOMANNAN; INFECTIONS; PRINCIPLES; BURDEN; ASSAYS; MODEL AB In this study we pursued a diagnostic target in Aspergillus fumigatus (AF) by using qualitative Realtime PCR combined with proprietary DNA primers and a hydrolysis probe specific for this fungal target. Qualitative Realtime PCR is a diagnostic tool that utilizes Realtime PCR technology and detects the presence or absence target specific DNA within a predetermined detection range. Respiratory tissue and fluids from experimentally infected guinea pigs were tested by extracting DNA from the samples which were amplified and detected using AF specific DNA primers and probe. This study included qualitative evaluations of all specimens for the presence of the DNA of AF. The findings in the tissues after AF infection were compared to the numbers of spores in aerosolized samples used to inoculate the animals. Results demonstrated that the specific probe and primer set could detect the presence or absence of AF DNA in the sample. The qualitative detection limit of the assay ranged from 6 x 10(4) copies to 6 copies. Since blood cultures are rarely positive for Aspergillosis, our data indicate that qualitative Realtime PCR, in combination with the appropriate DNA primers and probe can serve as an effective diagnostic tool in the early detection of fungal infections. C1 [Hooper, Dennis G.; Bolton, Vincent E.] RealTime Labs Inc, Carrollton, TX 75010 USA. [Sutton, John S.] S&S BioConsulting LLC, Austin, TX 78660 USA. [Guilford, Frederick T.] Your Energy Syst, Los Altos, CA 94022 USA. [Straus, David C.] Texas Tech Univ, Hlth Sci Ctr, Dept Microbiol & Immunol, Lubbock, TX 79430 USA. [Najvar, Laura K.; Wiederhold, Nathan P.; Kirkpatrick, William R.; Patterson, Thomas F.] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA. [Najvar, Laura K.; Kirkpatrick, William R.; Patterson, Thomas F.] S Texas Vet Hlth Care Syst, San Antonio, TX 78229 USA. [Wiederhold, Nathan P.] Univ Texas Austin, Coll Pharm, Div Pharmacotherapy, Austin, TX 78712 USA. RP Hooper, DG (reprint author), RealTime Labs Inc, 4100 Fairway Court,600, Carrollton, TX 75010 USA. EM dhooper@realtimelab.com OI Patterson, Thomas /0000-0002-9513-7127; Wiederhold, Nathan/0000-0002-2225-5122 NR 24 TC 0 Z9 0 U1 0 U2 8 PU MDPI AG PI BASEL PA POSTFACH, CH-4005 BASEL, SWITZERLAND SN 1661-6596 J9 INT J MOL SCI JI Int. J. Mol. Sci. PD JAN PY 2012 VL 13 IS 1 BP 726 EP 736 DI 10.3390/ijms13010726 PG 11 WC Biochemistry & Molecular Biology; Chemistry, Multidisciplinary SC Biochemistry & Molecular Biology; Chemistry GA 890ZE UT WOS:000300184800048 PM 22312282 ER PT J AU Izar, B Mannala, GK Abu Mraheil, M Chakraborty, T Hain, T AF Izar, Benjamin Mannala, Gopala Krishna Abu Mraheil, Mobarak Chakraborty, Trinad Hain, Torsten TI microRNA Response to Listeria monocytogenes Infection in Epithelial Cells SO INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES LA English DT Article DE Listeria monocytogenes; microRNA; non-coding RNA; infection; epithelial cells; Caco-2 ID HELICOBACTER-PYLORI INFECTION; INFLAMMATORY RESPONSE; NEGATIVELY MODULATE; EXPRESSION; INDUCTION; PROTEINS; INVASION; FAMILY AB microRNAs represent a family of very small non-coding RNAs that control several physiologic and pathologic processes, including host immune response and cancer by antagonizing a number of target mRNAs. There is limited knowledge about cell expression and the regulatory role of microRNAs following bacterial infections. We investigated whether infection with a Gram-positive bacterium leads to altered expression of microRNAs involved in the host cell response in epithelial cells. Caco-2 cells were infected with Listeria monocytogenes EGD-e, a mutant strain (Delta inlAB or Delta hly) or incubated with purified listeriolysin (LLO). Total RNA was isolated and microRNA and target gene expression was compared to the expression in non-infected cells using microRNA microarrays and qRT-PCR. We identified and validated five microRNAs (miR-146b, miR-16, let-7a1, miR-145 and miR-155) that were significantly deregulated following listerial infection. We show that expression patterns of particular microRNAs strongly depend on pathogen localization and the presence of bacterial effector proteins. Strikingly, miR-155 which was shown to have an important role in inflammatory responses during infection was induced by wild-type bacteria, by LLO-deficient bacteria and following incubation with purified LLO. It was downregulated following Delta inlAB infection indicating a new potent role for internalins in listerial pathogenicity and miRNA regulation. Concurrently, we observed differences in target transcript expression of the investigated miRNAs. We provide first evidence that L. monocytogenes infection leads to deregulation of a set of microRNAs with important roles in host response. Distinct microRNA expression depends on both LLO and pathogen localization. C1 [Izar, Benjamin; Mannala, Gopala Krishna; Abu Mraheil, Mobarak; Chakraborty, Trinad; Hain, Torsten] Univ Giessen, Inst Med Microbiol, D-35392 Giessen, Germany. [Izar, Benjamin] Massachusetts Gen Hosp, Dept Internal Med, Boston, MA 02118 USA. RP Hain, T (reprint author), Univ Giessen, Inst Med Microbiol, Frankfurter Str 107, D-35392 Giessen, Germany. EM bizar@partners.org; Gopala.K.Mannala@mikrobio.med.uni-giessen.de; Mobarak.Mraheil@mikrobio.med.uni-giessen.de; Trinad.Chakraborty@mikrobio.med.uni-giessen.de; Torsten.Hain@mikrobio.med.uni-giessen.de FU German Federal Ministry of Education and Research (BMBF, ERA-NET PathoGenomics Network) [0315437A, 0315907A] FX We would like to thank Alexandra Amend for technical assistance. This work was supported by the German Federal Ministry of Education and Research (BMBF, ERA-NET PathoGenomics Network projects sncRNAomics 0315437A to TH and LISTRESS 0315907A to TH and TC) and through the LOEWE program of the state Hessia by the collaborative research project Insect Biotechnology to TH and TC. NR 32 TC 24 Z9 29 U1 2 U2 20 PU MDPI AG PI BASEL PA POSTFACH, CH-4005 BASEL, SWITZERLAND SN 1661-6596 J9 INT J MOL SCI JI Int. J. Mol. Sci. PD JAN PY 2012 VL 13 IS 1 BP 1173 EP 1185 DI 10.3390/ijms13011173 PG 13 WC Biochemistry & Molecular Biology; Chemistry, Multidisciplinary SC Biochemistry & Molecular Biology; Chemistry GA 890ZE UT WOS:000300184800077 PM 22312311 ER PT J AU Papaspyridakos, P Chen, CJ Chuang, SK Weber, HP Gallucci, GO AF Papaspyridakos, Panos Chen, Chun-Jung Chuang, Sung-Kiang Weber, Hans-Peter Gallucci, German O. TI A Systematic Review of Biologic and Technical Complications with Fixed Implant Rehabilitations for Edentulous Patients SO INTERNATIONAL JOURNAL OF ORAL & MAXILLOFACIAL IMPLANTS LA English DT Article DE biologic complications; edentulism; implant-supported full-arch prosthesis; technical complications ID SUPPORTED MANDIBULAR PROSTHESES; 5-YEAR PROSPECTIVE MULTICENTER; LEAST 5 YEARS; FOLLOW-UP; ASTRA TECH; OBSERVATION PERIOD; DENTAL PROSTHESES; PARTIAL DENTURES; SURVIVAL; MAXILLA AB Purpose: The purpose of this systematic review was to assess the incidence and types of biologic and technical complications associated with implant-supported fixed complete dental prostheses (IFCDPs) for edentulous patients. Materials and Methods: An electronic MEDLINE/PubMED search was conducted to identify randomized controlled clinical trials and prospective cohort studies with IFCDPs for edentulous patients. Reports with at least 5 years of follow-up after prosthesis insertion were selected. Pooled data were analyzed statistically, and the cumulative complication rates were calculated by meta-analysis and regression. Results: Of a total of 281 one-piece IFCDPs (mean exposure time of 9.5 years) and 653 complication events, the complication rate was estimated at 24.6% per 100 restoration-years. The cumulative rates of "prosthesis free of complications" after 5 and 10 years were 29.3% and 8.6%, respectively. The most common implant-related biologic complication was peri-implant bone loss (> 2 mm), at rates of 20.1% after 5 years and 40.3% after 10 years. The most frequent implant-related technical complication was screw fracture, yielding a 5-year complication rate of 10.4% and a 10-year rate of 20.8%. The most frequent prosthesis-related biologic complication was hypertrophy or hyperplasia of tissue around the IFCDPs (13.0% and 26.0% after 5 and 10 years, respectively). The most common prosthesis-related technical complication reported with IFCDPs was chipping or fracture of the veneering material (33.3% at 5 years and 66.6% at 10 years). Conclusion: Biologic and technical complications after the placement of IFCDPs occur continuously over time as a result of fatigue and stress. These events may not lead to implant/prosthetic failures, but they are significant in relation to the amount of repair and maintenance needed, time, and cost to both the clinician and patient. INT J ORAL MAXILLOFAC IMPLANTS 2012;27:102-110 C1 [Papaspyridakos, Panos; Chen, Chun-Jung; Weber, Hans-Peter; Gallucci, German O.] Harvard Univ, Sch Dent Med, Dept Restorat Dent & Biomat Sci, Boston, MA 02115 USA. [Weber, Hans-Peter] Tufts Univ, Sch Dent Med, Dept Prosthodont & Operat Dent, Boston, MA 02111 USA. [Chuang, Sung-Kiang] Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Boston, MA 02114 USA. RP Gallucci, GO (reprint author), Harvard Univ, Sch Dent Med, Dept Restorat Dent & Biomat Sci, 188 Longwood Ave, Boston, MA 02115 USA. EM german_gallucci@hsdm.harvard.edu RI Gallucci, German/H-4505-2011 NR 38 TC 88 Z9 90 U1 1 U2 19 PU QUINTESSENCE PUBLISHING CO INC PI HANOVER PARK PA 4350 CHANDLER DRIVE, HANOVER PARK, IL 60133 USA SN 0882-2786 J9 INT J ORAL MAX IMPL JI Int. J. Oral Maxillofac. Implants PD JAN-FEB PY 2012 VL 27 IS 1 BP 102 EP 110 PG 9 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 893WZ UT WOS:000300389700013 PM 22299086 ER PT J AU Ladapo, JA David, G Gunnarsson, CL Hao, SC White, SA March, JL Reynolds, MR AF Ladapo, Joseph A. David, Guy Gunnarsson, Candace L. Hao, Steven C. White, Sarah A. March, Jamie L. Reynolds, Matthew R. TI Healthcare Utilization and Expenditures in Patients with Atrial Fibrillation Treated with Catheter Ablation SO JOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY LA English DT Article DE atrial fibrillation; catheter ablation; healthcare expenditures; health policy; healthcare utilization; MarketScan; Medicare Supplemental Database ID ANTIARRHYTHMIC-DRUG THERAPY; COST-EFFECTIVENESS; UNITED-STATES; LONG-TERM; RADIOFREQUENCY ABLATION; POPULATION; PREVALENCE; MORTALITY; FLUTTER; TRIAL AB Catheter Ablation in AF Patients, Including Age 65+, Reduces Utilization. Aim: The aim was to estimate the impact of catheter ablation on short- and long-term healthcare utilization and expenditures among atrial fibrillation (AF) patients in general and Medicare populations. Methods: Data were analyzed from TheMarketScan (R) Databases. MarketScan data contain deidentified patient-level records from employer-sponsored and public health insurance plans. Multivariable regression models for utilization and expenditures were built for all patients, with subanalyses performed for patients >= 65 years. Results were compared to preablation figures and reported for 5 time groups, based on duration of available postablation follow-up: 6-12 months; 12-18 months; 18-24 months; 24-30 months; and 30-36 months. Results: A total of 3,194 patients were identified who had undergone catheter ablation for treatment of AF, had continuous enrollment in the database 6 months prior to first ablation, and had at least 1-year follow-up postablation. Compared to the 6 months prior to ablation, there were significant reductions in the number of outpatient appointments, inpatient days, and emergency room visits in the total study population and in the subset >= 65 years. There was a statistically significant (P < 0.01) decrease in total healthcare expenditures across 4 of the 5 6-month time periods, with annual savings ranging from $ 3,300 to $ 9,200. For patients >= 65 years, annual savings ranged from $3,200 to $9,200. Drug utilization also significantly declined (P < 0.01), with average annual medication savings ranging from $670 to $890, and from $740 to $880 for patients >= 65 years. Conclusion: Catheter ablation for AF reduced healthcare utilization and expenditures up to 3 years postablation. This reduction was consistent, significant, and had implications for general and Medicare populations. (J Cardiovasc Electrophysiol, Vol. 23, pp. 1-8, January 2012) C1 [Ladapo, Joseph A.] Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA 02215 USA. [Ladapo, Joseph A.] Harvard Univ, Sch Med, Boston, MA USA. [David, Guy] Univ Penn, Philadelphia, PA 19104 USA. [Gunnarsson, Candace L.] S2 Stat Solut Inc, Cincinnati, OH USA. [Hao, Steven C.] Sutter Pacific Med Fdn, San Francisco, CA USA. [White, Sarah A.; March, Jamie L.] Biosense Webster Inc, Diamond Bar, CA USA. [Reynolds, Matthew R.] VA Boston Hlth Care Syst, Boston, MA USA. RP Ladapo, JA (reprint author), Beth Israel Deaconess Med Ctr, Dept Med, 330 Brookline Ave, Boston, MA 02215 USA. EM jladapo@post.harvard.edu OI Ladapo, Joseph/0000-0002-8518-4800 FU Biosense Webster, Inc. FX This study was funded by Biosense Webster, Inc. NR 35 TC 10 Z9 10 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1045-3873 J9 J CARDIOVASC ELECTR JI J. Cardiovasc. Electrophysiol. PD JAN PY 2012 VL 23 IS 1 BP 1 EP 8 DI 10.1111/j.1540-8167.2011.02130.x PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 877CY UT WOS:000299155700001 PM 21777324 ER PT J AU Keating, NL Malin, JL AF Keating, Nancy L. Malin, Jennifer L. TI Providing Cancer Care: Individual or Team Sport? SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Editorial Material ID MEDICAL HOME C1 [Keating, Nancy L.] Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. [Keating, Nancy L.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Gen Internal Med, Boston, MA 02115 USA. [Malin, Jennifer L.] W Los Angeles Vet Affairs Med Ctr, Los Angeles, CA USA. RP Keating, NL (reprint author), Harvard Univ, Sch Med, Dept Hlth Care Policy, 180 Longwood Ave, Boston, MA 02115 USA. EM keating@hcp.med.harvard.edu NR 11 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JAN PY 2012 VL 27 IS 1 BP 3 EP 4 DI 10.1007/s11606-011-1922-3 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 873LD UT WOS:000298883900002 PM 22086752 ER PT J AU Brown, RT Kiely, DK Bharel, M Mitchell, SL AF Brown, Rebecca T. Kiely, Dan K. Bharel, Monica Mitchell, Susan L. TI Geriatric Syndromes in Older Homeless Adults SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE homeless persons; aged; geriatric syndromes ID MINI-MENTAL-STATE; ELDERLY PERSONS; SAN-FRANCISCO; HEALTH-STATUS; POPULATION; FALLS; PREDICTORS; ACCURACY; INDEX; NEEDS AB The average age of the US homeless population is increasing. Little is known about the prevalence of geriatric syndromes in older homeless adults. To determine the prevalence of common geriatric syndromes in a sample of older homeless adults, and to compare these prevalences to those reported in the general older population. Cross-sectional. Two hundred and forty-seven homeless adults aged 50-69 recruited from eight homeless shelters in Boston, MA. Interviews and examinations for geriatric syndromes, including functional impairment, cognitive impairment, frailty, depression, hearing impairment, visual impairment, and urinary incontinence. The prevalences of these syndromes in the homeless cohort were compared to those reported in three population-based cohorts. The mean age of the homeless cohort was 56.0 years, and 19.8% were women. Thirty percent of subjects reported difficulty performing at least one activity of daily living, and 53.2% fell in the prior year. Cognitive impairment, defined as a Mini-Mental State Examination score < 24, was present in 24.3% of participants; impaired executive function, defined as a Trail Making Test Part B duration > 1.5 standard deviations above population-based norms, was present in 28.3% of participants. Sixteen percent of subjects met criteria for frailty, and 39.8% had major depression, defined as a score a parts per thousand yen10 on the Patient Health Questionnaire 9. Self-reported hearing and visual impairment was present among 29.7% and 30.0% of subjects, respectively. Urinary incontinence was reported by 49.8% of subjects. After multivariate adjustment for demographic characteristics, homeless adults were more likely to have functional impairment, frailty, depression, visual impairment and urinary incontinence compared to three population-based cohorts of older persons. Geriatric syndromes that are potentially amenable to treatment are common in older homeless adults, and are experienced at higher rates than in the general older population. C1 [Brown, Rebecca T.; Kiely, Dan K.; Mitchell, Susan L.] Hebrew SeniorLife Inst Aging Res, Boston, MA 02131 USA. [Brown, Rebecca T.; Mitchell, Susan L.] Beth Israel Deaconess Med Ctr, Div Gerontol, Boston, MA 02215 USA. [Bharel, Monica] Boston Healthcare Homeless Program, Boston, MA USA. [Bharel, Monica] Boston Med Ctr, Dept Med, Boston, MA USA. [Bharel, Monica] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. RP Brown, RT (reprint author), Hebrew SeniorLife Inst Aging Res, 1200 Ctr St, Boston, MA 02131 USA. EM rebeccabrown@hsl.harvard.edu FU Hartford Foundation; NIH-NIA [T32 AG023480, AG004390, K24 AG033640]; HRCA FX We thank the data management team(Margaret Bryan, Ellen Gornstein, Diane Engorn); Michele Shaffer, PhD, for statistical consultation; the staff at participating shelters; and the subjects who generously gave their time to this study. This work was supported by the Hartford Foundation, NIH-NIA T32 AG023480, and the HRCA/Harvard Research Nursing Home Program Project, funded by NIH-NIA AG004390. Dr. Mitchell was supported by NIH-NIA K24 AG033640. NR 40 TC 37 Z9 38 U1 2 U2 10 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JAN PY 2012 VL 27 IS 1 BP 16 EP 22 DI 10.1007/s11606-011-1848-9 PG 7 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 873LD UT WOS:000298883900006 PM 21879368 ER PT J AU Kind, AJH Thorpe, CT Sattin, JA Walz, SE Smith, MA AF Kind, Amy J. H. Thorpe, Carolyn T. Sattin, Justin A. Walz, Stacy E. Smith, Maureen A. TI Provider Characteristics, Clinical-Work Processes and Their Relationship to Discharge Summary Quality for Sub-Acute Care Patients SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE discharge documentation; hospital discharge quality; discharge summary; transitions in care; work processes ID HOSPITAL DISCHARGE; GENERAL-PRACTITIONERS; INTERNAL-MEDICINE; STROKE; COMMUNICATION; TRANSITIONS; CONTINUITY; PHYSICIANS; SAFETY; HOME AB Discharge summaries play a pivotal role in the transitional care of patients discharged to sub-acute care facilities, but the best ways to facilitate document completeness/quality remain unknown. To examine the relationship among clinical-work processes, provider characteristics, and discharge summary content to identify approaches that promote high-quality discharge documentation. Retrospective cohort study. All hip fracture and stroke patients discharged to sub-acute care facilities during 2003-2005 from a large Midwestern academic medical center (N = 489). Patients on hospice/comfort care were excluded. We abstracted 32 expert-recommended components in four categories ('patient's medical course,' 'functional/cognitive ability at discharge,' 'future plan of care,' and 'name/contact information') from the discharge summaries of sample patients. We examined predictors for the number of included components within each category using Poisson regression models. Predictors included work processes (document completion in relation to discharge day; completion time of day) and provider characteristics (training year; specialty). Historical components (i.e., 'patient's medical course' category) were included more often than components that directly inform the admission orders in the sub-acute care facility (i.e., 'future plan of care'). In this latter category, most summaries included a discharge medication list (99%), disposition (90%), and instructions for follow-up (91%), but less frequently included diet (68%), activity instructions (58%), therapy orders (56%), prognosis/diagnosis communication to patient/family (15%), code status (7%), and pending studies (6%). 'Future plan of care' components were more likely to be omitted if a discharge summary was created > 24 h after discharge (incident rate ratio = 0.91, 95% confidence interval = 0.84-0.98) or if an intern created the summary (0.90, 0.83-0.97). Critical component omissions in discharge summaries were common, and were associated with delayed document creation and less experienced providers. More research is needed to understand the impact of discharge documentation quality on patient/system outcomes. C1 [Kind, Amy J. H.] William S Middleton Hosp, US Dept Vet Affairs, Geriatr Res Educ & Clin Ctr GRECC, Madison, WI 53705 USA. [Kind, Amy J. H.] Univ Wisconsin, Dept Med, Sch Med & Publ Hlth, Div Geriatr, Madison, WI USA. [Thorpe, Carolyn T.; Walz, Stacy E.; Smith, Maureen A.] Univ Wisconsin, Sch Med & Publ Hlth, Dept Populat Hlth Sci, Madison, WI USA. [Sattin, Justin A.] Univ Wisconsin, Dept Neurol, Sch Med & Publ Hlth, Madison, WI 53706 USA. [Walz, Stacy E.] Univ Wisconsin, Sch Med & Publ Hlth, Dept Pathol & Lab Med, Madison, WI USA. [Smith, Maureen A.] Univ Wisconsin, Sch Med & Publ Hlth, Dept Family Med, Madison, WI USA. [Smith, Maureen A.] Univ Wisconsin, Dept Surg, Sch Med & Publ Hlth, Madison, WI USA. RP Kind, AJH (reprint author), William S Middleton Hosp, US Dept Vet Affairs, Geriatr Res Educ & Clin Ctr GRECC, 2500 Overlook Terrace, Madison, WI 53705 USA. EM ajk@medicine.wisc.edu FU National Institute on Aging [K23AG034551]; National Institute of Health [1KL2RR025012-01, 1UL1RR025011]; National Center for Research Resources, National Institutes of Health [1UL1RR025011] FX This project was supported by a National Institute on Aging Beeson Career Development Award (K23AG034551, National Institute on Aging, The American Federation for Aging Research, The John A. Hartford Foundation, The Atlantic Philanthropies, and The Starr Foundation) and by a K-L2 through the National Institute of Health grant 1KL2RR025012-01 [Institutional Clinical and Translational Science Award (UW-Madison) 1UL1RR025011 (KL2) program of the National Center for Research Resources, National Institute of Health]. Additional support was provided by the University of Wisconsin (UW) Hartford Center of Excellence in Geriatrics, the UW School of Medicine and Public Health from The Wisconsin Partnership Program, the Health Innovation Program, the UW Hospitals and Clinics, and the Community-Academic Partnerships core of the University of Wisconsin Institute for Clinical and Translational Research (UW ICTR), grant 1UL1RR025011 from the Clinical and Translational Science Award (CTSA) program of the National Center for Research Resources, National Institutes of Health. The Health Innovation Program assisted with data management and with manuscript formatting. No other funding source had a role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; or preparation, review, or approval of the manuscript. NR 26 TC 21 Z9 22 U1 2 U2 6 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JAN PY 2012 VL 27 IS 1 BP 78 EP 84 DI 10.1007/s11606-011-1860-0 PG 7 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 873LD UT WOS:000298883900015 PM 21901489 ER PT J AU Wright, A Poon, EG Wald, J Feblowitz, J Pang, JE Schnipper, JL Grant, RW Gandhi, TK Volk, LA Bloom, A Williams, DH Gardner, K Epstein, M Nelson, L Businger, A Li, Q Bates, DW Middleton, B AF Wright, Adam Poon, Eric G. Wald, Jonathan Feblowitz, Joshua Pang, Justine E. Schnipper, Jeffrey L. Grant, Richard W. Gandhi, Tejal K. Volk, Lynn A. Bloom, Amy Williams, Deborah H. Gardner, Kate Epstein, Marianna Nelson, Lisa Businger, Alex Li, Qi Bates, David W. Middleton, Blackford TI Randomized Controlled Trial of Health Maintenance Reminders Provided Directly to Patients Through an Electronic PHR SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE health maintenance reminders; personal health record; preventive care; clinical decision support; Patient Gateway ID MAMMOGRAPHY USE; PRIMARY-CARE; INTERVENTIONS; QUALITY; RECORDS; DISEASE AB Provider and patient reminders can be effective in increasing rates of preventive screenings and vaccinations. However, the effect of patient-directed electronic reminders is understudied. To determine whether providing reminders directly to patients via an electronic Personal Health Record (PHR) improved adherence to care recommendations. We conducted a cluster randomized trial without blinding from 2005 to 2007 at 11 primary care practices in the Partners HealthCare system. A total of 21,533 patients with access to a PHR were invited to the study, and 3,979 (18.5%) consented to enroll. Patients in the intervention arm received health maintenance (HM) reminders via a secure PHR "eJournal," which allowed them to review and update HM and family history information. Patients in the active control arm received access to an eJournal that allowed them to input and review information related to medications, allergies and diabetes management. The primary outcome measure was adherence to guideline-based care recommendations. Intention-to-treat analysis showed that patients in the intervention arm were significantly more likely to receive mammography (48.6% vs 29.5%, p = 0.006) and influenza vaccinations (22.0% vs 14.0%, p = 0.018). No significant improvement was observed in rates of other screenings. Although Pap smear completion rates were higher in the intervention arm (41.0% vs 10.4%, p < 0.001), this finding was no longer significant after excluding women's health clinics. Additional on-treatment analysis showed significant increases in mammography (p = 0.019) and influenza vaccination (p = 0.015) for intervention arm patients who opened an eJournal compared to control arm patients, but no differences for any measure among patients who did not open an eJournal. Providing patients with HM reminders via a PHR may be effective in improving some elements of preventive care. C1 [Wright, Adam; Poon, Eric G.; Wald, Jonathan; Feblowitz, Joshua; Pang, Justine E.; Schnipper, Jeffrey L.; Gandhi, Tejal K.; Williams, Deborah H.; Businger, Alex; Bates, David W.; Middleton, Blackford] Brigham & Womens Hosp, Boston, MA 02115 USA. [Wright, Adam; Poon, Eric G.; Wald, Jonathan; Feblowitz, Joshua; Pang, Justine E.; Schnipper, Jeffrey L.; Gandhi, Tejal K.; Volk, Lynn A.; Bloom, Amy; Gardner, Kate; Epstein, Marianna; Nelson, Lisa; Businger, Alex; Li, Qi; Bates, David W.; Middleton, Blackford] Partners HealthCare, Boston, MA USA. [Wright, Adam; Poon, Eric G.; Wald, Jonathan; Grant, Richard W.; Gandhi, Tejal K.; Bates, David W.; Middleton, Blackford] Harvard Univ, Sch Med, Boston, MA USA. [Grant, Richard W.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Wright, A (reprint author), Brigham Womens Hosp, 1620 Tremont St, Boston, MA 02115 USA. EM awright5@partners.org OI Feblowitz, Joshua/0000-0002-8750-859X; Grant, Richard/0000-0002-6164-8025 FU AHRQ [R01-HS013660-02] FX This work was partially supported by AHRQ Grant R01-HS013660-02: Shared Online Health Records for Patient Safety and Quality. AHRQ was not involved in the design, execution or analysis of the study, or in the preparation of this manuscript. The study protocol was approved by the Partners HealthCare Human Research Committee and registered at ClinicalTrials.gov (NCT00251875). NR 28 TC 22 Z9 22 U1 4 U2 10 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JAN PY 2012 VL 27 IS 1 BP 85 EP 92 DI 10.1007/s11606-011-1859-6 PG 8 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 873LD UT WOS:000298883900016 PM 21904945 ER PT J AU Minemura, N Dhaliwal, G Tierney, LM AF Minemura, Nobuyoshi Dhaliwal, Gurpreet Tierney, Lawrence M., Jr. TI Against All Odds SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Editorial Material DE clinical reasoning ID TUBERCULOUS MYOSITIS; PATIENT; ENTITY C1 [Minemura, Nobuyoshi] Natl Sanat Tama Zenshoen, Div Internal Med, Higashimurayama, Tokyo 1898550, Japan. [Dhaliwal, Gurpreet; Tierney, Lawrence M., Jr.] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. [Dhaliwal, Gurpreet; Tierney, Lawrence M., Jr.] San Francisco VA Med Ctr, San Francisco, CA USA. RP Minemura, N (reprint author), Natl Sanat Tama Zenshoen, Div Internal Med, 4-1-1 Aoba Cho, Higashimurayama, Tokyo 1898550, Japan. EM ici01059@mbj.nifty.com NR 10 TC 0 Z9 0 U1 1 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JAN PY 2012 VL 27 IS 1 BP 125 EP 128 DI 10.1007/s11606-011-1830-6 PG 4 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 873LD UT WOS:000298883900023 PM 21879373 ER PT J AU Szecket, N Wong, HJ Wu, RC Berman, HD Morra, D AF Szecket, Nicolas Wong, Hannah J. Wu, Robert C. Berman, Hershl D. Morra, Dante TI Implementation of a continuous admission model reduces the length of stay of patients on an internal medicine clinical teaching unit SO JOURNAL OF HOSPITAL MEDICINE LA English DT Article ID DISCHARGE; SERVICE; SATISFACTION; EFFICIENCY; WORKLOAD; OUTCOMES; IMPACT; CARE AB BACKGROUND: Optimizing hospital operations is a critical issue facing healthcare systems. Reducing unnecessary variation in patient flow is likely to improve efficiency and optimize capacity for hospital inpatients. The objective of this study was to determine whether changing admissions, from a bolus system to a drip system, would result in a smoothed daily discharge rate, and reduce the length of stay of patients on a General Internal Medicine clinical teaching unit over a period of 1 year. METHODS: We conducted a retrospective analysis of the General Internal Medicine inpatient service at Toronto General Hospital for the 6-month periods from March to August during 2 consecutive years. Length of stay distributions and daily discharge rate variations were compared between the 2 study periods. RESULTS: There were a total of 2734 discharges, 1446 occurring in the pre-change period, and 1288 in the post-change period. There was overall smoothing of the daily discharge rates, and a reduction of 0.3 days in median length of stay in the post-change period (P = 0.0065). CONCLUSIONS: Restructuring the admission system to achieve constant daily admissions to each care team resulted in a smoothing of daily discharge rates and improved operational efficiency with shorter lengths of stay. Journal of Hospital Medicine 2012;7:55-59. (C) 2011 Society of Hospital Medicine. C1 [Szecket, Nicolas; Wong, Hannah J.; Wu, Robert C.; Berman, Hershl D.; Morra, Dante] Univ Toronto, Univ Hlth Network, Ctr Innovat Complex Care, Toronto, ON, Canada. [Wong, Hannah J.] Massachusetts Gen Hosp, Inst Technol Assessment, Boston, MA 02114 USA. [Wong, Hannah J.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Wong, Hannah J.] Harvard Univ, Sch Med, Boston, MA USA. RP Szecket, N (reprint author), Auckland City Hosp, Level 6,Support Bldg, Auckland, New Zealand. EM nicolas.szecket@utoronto.ca OI Wong, Hannah/0000-0002-9740-0312 NR 18 TC 4 Z9 4 U1 0 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1553-5592 J9 J HOSP MED JI J. Hosp. Med. PD JAN PY 2012 VL 7 IS 1 BP 55 EP 59 DI 10.1002/jhm.926 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA 871IX UT WOS:000298732600010 PM 21954169 ER PT J AU Kim, J Hegde, M Kim, SH Wood, TK Jayaraman, A AF Kim, Jeongyun Hegde, Manjunath Kim, Sun Ho Wood, Thomas K. Jayaraman, Arul TI A microfluidic device for high throughput bacterial biofilm studies SO LAB ON A CHIP LA English DT Article ID ESCHERICHIA-COLI BIOFILMS; MICROBIAL BIOFILMS; INDOLE; INFECTIONS; EXPRESSION; 7-HYDROXYINDOLE; MONOOXYGENASE; CHEMOTAXIS; OXIDATION; CANCER AB Bacteria are almost always found in ecological niches as matrix-encased, surface-associated, multi-species communities known as biofilms. It is well established that soluble chemical signals produced by the bacteria influence the organization and structure of the biofilm; therefore, there is significant interest in understanding how different chemical signals are coordinately utilized for community development. Conventional methods for investigating biofilm formation such as macro-scale flow cells are low-throughput, require large volumes, and do not allow spatial and temporal control of biofilm community formation. Here, we describe the development of a PDMS-based two-layer microfluidic flow cell (mu FC) device for investigating bacterial biofilm formation and organization in response to different concentrations of soluble signals. The mFC device contains eight separate microchambers for cultivating biofilms exposed to eight different concentrations of signals through a single diffusive mixing-based concentration gradient generator. The presence of pneumatic valves and a separate cell seeding port that is independent from gradient-mixing channels offers complete isolation of the biofilm microchamber from the gradient mixer, and also performs well under continuous, batch or semi-batch conditions. We demonstrate the utility of the mu FC by studying the effect of different concentrations of indole-like biofilm signals (7-hydroxyindole and isatin), either individually or in combination, on biofilm development of pathogenic E. coli. This model can be used for developing a fundamental understanding of events leading to bacterial attachment to surfaces that are important in infections and chemicals that influence the biofilm formation or inhibition. C1 [Kim, Jeongyun; Hegde, Manjunath; Wood, Thomas K.; Jayaraman, Arul] Texas A&M Univ, Dept Chem Engn, College Stn, TX 77843 USA. [Kim, Sun Ho] Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA. RP Jayaraman, A (reprint author), Texas A&M Univ, Dept Chem Engn, 222 Jack E Brown Engn Bldg, College Stn, TX 77843 USA. EM arulj@tamu.edu RI Hegde, Manjunath/M-3038-2014; OI Hegde, Manjunath/0000-0002-5396-2241; Wood, Thomas/0000-0002-6258-529X FU National Institutes of Health [R01 GM089999]; National Science Foundation [CBET 0846453] FX This work was supported by grants from the National Institutes of Health (R01 GM089999) to TKW and AJ and the National Science Foundation (CBET 0846453) to AJ. We thank Dr Tarun Bansal for constructing the EHEC Delta tnaA mutant used in this study. NR 42 TC 26 Z9 26 U1 0 U2 61 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 1473-0197 EI 1473-0189 J9 LAB CHIP JI Lab Chip PY 2012 VL 12 IS 6 BP 1157 EP 1163 DI 10.1039/c2lc20800h PG 7 WC Biochemical Research Methods; Chemistry, Multidisciplinary; Nanoscience & Nanotechnology SC Biochemistry & Molecular Biology; Chemistry; Science & Technology - Other Topics GA 895QO UT WOS:000300511500020 PM 22318368 ER PT J AU Chang, TI Tanner, JM Harada, ND Garrett, NR Friedlander, AH AF Chang, Tina I. Tanner, Jeffrey M. Harada, Nancy D. Garrett, Neal R. Friedlander, Arthur H. TI Prevalence of calcified carotid artery atheromas on the panoramic images of patients with syndrome Z, coexisting obstructive sleep apnea, and metabolic syndrome SO ORAL SURGERY ORAL MEDICINE ORAL PATHOLOGY ORAL RADIOLOGY LA English DT Article ID CORONARY-HEART-DISEASE; CARDIOVASCULAR-DISEASE; INSULIN-RESISTANCE; RISK-FACTORS; FOLLOW-UP; INTERMITTENT HYPOXIA; OXIDATIVE STRESS; BLOOD-PRESSURE; ATHEROSCLEROSIS; ADULTS AB Objectives. The objective of this study was to compare the prevalence of calcified carotid artery atheromas (CCAAs) on panoramic images of individuals (n = 31) with obstructive sleep apnea (OSA) with individuals (n = 117) with syndrome Z (SZ: OSA with concomitant metabolic syndrome [MetS]). Study design. Images of patients with OSA or SZ referred from the Sleep Service to Dentistry were evaluated. Descriptive statistics and t tests (Bonferroni correction) were conducted to determine significant differences between atheroma prevalence and proatherogenic factors (age, apnea-hypopnea index, body mass index, lipid profile, blood pressure, glucose) between OSA and SZ groups. Results. Individuals with OSA had an atheroma prevalence of 35% and those with SZ 42% (P = .52). Individuals with SZ also had significantly more severe atherogenic profiles (obesity, dyslipidemia, hyperglycemia) than OSA patients (P <= .05). Greatest CCAA prevalence (63%) was evidenced by SZ patients with severe OSA and moderate MetS. Conclusion. Individuals with SZ have significantly greater atherogenic burden and slightly higher prevalence of CCAAs when compared with individuals with OSA. (Oral Surg Oral Med Oral Pathol Oral Radiol 2012;113:134-141) C1 [Tanner, Jeffrey M.; Friedlander, Arthur H.] VA Greater Los Angeles Healthcare Syst, Dent Serv, Oral & Maxillofacial Surg Sect, Los Angeles, CA 90073 USA. [Harada, Nancy D.] Vet Affairs Greater Los Angeles Healthcare Syst, Geriatr Res Educ & Clin Ctr, Los Angeles, CA 90073 USA. [Garrett, Neal R.] Univ Calif Los Angeles, Sch Dent, Div Adv Prosthodont Biomat & Hosp Dent, Los Angeles, CA 90024 USA. [Harada, Nancy D.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Friedlander, Arthur H.] Ronald Reagan UCLA Med Ctr, Hosp Dent Serv, Torrance, CA USA. RP Friedlander, AH (reprint author), VA Greater Los Angeles Healthcare Syst, Dent Serv, Oral & Maxillofacial Surg Sect, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM arthur.friedlander@va.gov FU Department of Veterans Affairs; University of California; National Center for Research Resources, National Institutes of Health [C06 RR-14529-01] FX The financial support of this project was limited to the full-time salaries paid to the authors by the Department of Veterans Affairs and the University of California. Elements of this investigation were conducted in a facility constructed with support from Research Facilities Improvement Program Grant Number C06 RR-14529-01 from the National Center for Research Resources, National Institutes of Health. NR 59 TC 1 Z9 2 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 2212-4403 J9 OR SURG OR MED OR PA JI Oral Surg. Oral Med. Oral Pathol. Oral Radiol. PD JAN PY 2012 VL 113 IS 1 BP 134 EP 141 DI 10.1016/j.tripleo.2011.07.039 PG 8 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 898ZW UT WOS:000300781900016 PM 22669072 ER PT B AU Spitz, DR McCormick, ML Oberley, TD AF Spitz, Douglas R. McCormick, Michael L. Oberley, Terry D. BE Spitz, DR Dornfeld, KJ Krishnan, K Gius, D TI Oxidative Stress in Cancer Biology and Therapy Preface SO OXIDATIVE STRESS IN CANCER BIOLOGY AND THERAPY SE Oxidative Stress in Applied Basic Research and Clinical Practice LA English DT Editorial Material; Book Chapter ID HUMAN TUMOR-CELLS; DEPRIVATION-INDUCED CYTOTOXICITY; GLUCOSE DEPRIVATION; SUPEROXIDE-DISMUTASE; HYDROGEN-PEROXIDE; H2O2 MEDIATE; ENZYMOLOGY C1 [Spitz, Douglas R.; McCormick, Michael L.] Univ Iowa, Free Rad & Radiat Biol Program, Dept Radiat Oncol, Holden Comprehens Canc Ctr, Iowa City, IA 52242 USA. [Oberley, Terry D.] Univ Wisconsin, Mol & Environm Toxicol Ctr, Sch Med & Publ Hlth, Madison, WI USA. [Oberley, Terry D.] Univ Wisconsin, Dept Pathol & Lab Med, Sch Med & Publ Hlth, Madison, WI USA. [Oberley, Terry D.] William S Middleton Mem Vet Adm Med Ctr, Pathol & Lab Med Serv, Madison, WI 53705 USA. RP Spitz, DR (reprint author), Univ Iowa, Free Rad & Radiat Biol Program, Dept Radiat Oncol, Holden Comprehens Canc Ctr, Iowa City, IA 52242 USA. NR 19 TC 2 Z9 2 U1 0 U2 0 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY BN 978-1-61779-396-7 J9 OXID STRESS APPL BAS JI Oxid. Stress Appl. Basic Res. Clin. Pract. PY 2012 BP V EP VII D2 10.1007/978-1-61779-397-4 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA BYQ04 UT WOS:000299709300001 ER PT B AU Shan, WH Zhong, WX Swanlund, J Oberley, TD AF Shan, Weihua Zhong, Weixiong Swanlund, Jamie Oberley, Terry D. BE Spitz, DR Dornfeld, KJ Krishnan, K Gius, D TI Oxidative Stress in Prostate Cancer SO OXIDATIVE STRESS IN CANCER BIOLOGY AND THERAPY SE Oxidative Stress in Applied Basic Research and Clinical Practice LA English DT Article; Book Chapter ID MANGANESE SUPEROXIDE-DISMUTASE; CARCINOMA-CELL-LINES; FACTOR-KAPPA-B; REACTIVE OXYGEN; INTRAEPITHELIAL NEOPLASIA; ANTIOXIDANT ENZYMES; PROTEIN EXPRESSION; ANDROGEN RECEPTOR; HYDROGEN-PEROXIDE; SEQUENCE VARIANTS AB Prostate cancer primarily affects older men and is the second leading cause of cancer deaths in males in the USA. Known risk factors for prostate carcinogenesis include age, race, and family history, while possible risk factors include diet, lifestyle, androgens, and inflammation. At least three of these known or potential risk factors (androgens, inflammation, and age) are indirectly linked by the fact that each may result in and/or be derived from oxidative stress. Low levels of reactive oxygen species (ROS) participate in many important physiological and pathological processes in the cell, including proliferation, cell cycle progression, migration, angiogenesis, invasion/metastasis, and inhibition of apoptosis, features that cancer cells might regulate to facilitate progression to a more aggressive phenotype. High levels of ROS/oxidative stress are capable of causing damage to various cellular constituents, including DNA, proteins, and lipids. Elevated levels of ROS, due to increased ROS production or impaired antioxidant defense systems, have been implicated in prostate carcinogenesis. Specific redox compartmental oxidation, which is believed to function as a mechanism for specificity in redox signaling and oxidative stress, is also manifested in prostate cancer. In this chapter, we present and analyze recent findings and ideas relating oxidative stress to prostate cancer and discuss their implications for future studies. C1 [Shan, Weihua; Oberley, Terry D.] Univ Wisconsin, Mol & Environm Toxicol Ctr, Sch Med & Publ Hlth, Madison, WI 53706 USA. [Zhong, Weixiong; Oberley, Terry D.] Univ Wisconsin, Dept Pathol & Lab Med, Sch Med & Publ Hlth, Madison, WI USA. [Zhong, Weixiong; Swanlund, Jamie; Oberley, Terry D.] William S Middleton Mem Vet Adm Med Ctr, Pathol & Lab Med Serv, Madison, WI 53705 USA. RP Oberley, TD (reprint author), Univ Wisconsin, Mol & Environm Toxicol Ctr, Sch Med & Publ Hlth, Madison, WI 53706 USA. EM toberley@wisc.edu NR 153 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY BN 978-1-61779-396-7 J9 OXID STRESS APPL BAS JI Oxid. Stress Appl. Basic Res. Clin. Pract. PY 2012 BP 301 EP 331 DI 10.1007/978-1-61779-397-4_15 D2 10.1007/978-1-61779-397-4 PG 31 WC Medicine, General & Internal SC General & Internal Medicine GA BYQ04 UT WOS:000299709300016 ER PT J AU Cheng, YK Beroukhim, R Levine, RL Mellinghoff, IK Holland, EC Michor, F AF Cheng, Yu-Kang Beroukhim, Rameen Levine, Ross L. Mellinghoff, Ingo K. Holland, Eric C. Michor, Franziska TI A Mathematical Methodology for Determining the Temporal Order of Pathway Alterations Arising during Gliomagenesis SO PLOS COMPUTATIONAL BIOLOGY LA English DT Article ID COMPARATIVE GENOMIC HYBRIDIZATION; ONCOGENETIC TREE MODEL; SECONDARY GLIOBLASTOMAS; ANAPLASTIC ASTROCYTOMA; SPONTANEOUS MUTATION; GENETIC INSTABILITY; CANCER PROGRESSION; CORE PATHWAYS; GLIOMA; TUMORS AB Human cancer is caused by the accumulation of genetic alterations in cells. Of special importance are changes that occur early during malignant transformation because they may result in oncogene addiction and thus represent promising targets for therapeutic intervention. We have previously described a computational approach, called Retracing the Evolutionary Steps in Cancer (RESIC), to determine the temporal sequence of genetic alterations during tumorigenesis from cross-sectional genomic data of tumors at their fully transformed stage. Since alterations within a set of genes belonging to a particular signaling pathway may have similar or equivalent effects, we applied a pathway-based systems biology approach to the RESIC methodology. This method was used to determine whether alterations of specific pathways develop early or late during malignant transformation. When applied to primary glioblastoma (GBM) copy number data from The Cancer Genome Atlas (TCGA) project, RESIC identified a temporal order of pathway alterations consistent with the order of events in secondary GBMs. We then further subdivided the samples into the four main GBM subtypes and determined the relative contributions of each subtype to the overall results: we found that the overall ordering applied for the proneural subtype but differed for mesenchymal samples. The temporal sequence of events could not be identified for neural and classical subtypes, possibly due to a limited number of samples. Moreover, for samples of the proneural subtype, we detected two distinct temporal sequences of events: (i) RAS pathway activation was followed by TP53 inactivation and finally PI3K2 activation, and (ii) RAS activation preceded only AKT activation. This extension of the RESIC methodology provides an evolutionary mathematical approach to identify the temporal sequence of pathway changes driving tumorigenesis and may be useful in guiding the understanding of signaling rearrangements in cancer development. C1 [Cheng, Yu-Kang; Michor, Franziska] Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Cheng, Yu-Kang; Michor, Franziska] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Cheng, Yu-Kang; Holland, Eric C.] Mem Sloan Kettering Canc Ctr, Brain Tumor Ctr, Canc Biol & Genet Program, New York, NY 10021 USA. [Cheng, Yu-Kang] Weill Cornell Med Coll, Tri Inst Training Program Computat Biol & Med, New York, NY USA. [Beroukhim, Rameen] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. [Beroukhim, Rameen] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Beroukhim, Rameen] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Beroukhim, Rameen] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Beroukhim, Rameen] Broad Inst MIT & Harvard, Canc Program, Cambridge, MA USA. [Levine, Ross L.; Mellinghoff, Ingo K.] Mem Sloan Kettering Canc Ctr, Human Oncol & Pathogenesis Program, New York, NY 10021 USA. RP Cheng, YK (reprint author), Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. EM michor@jimmy.harvard.edu FU NIH [U54CA143798] FX NIH U54CA143798: Evolutionary Dynamics of Brain, Lung, and Hematopoietic Tumors. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 71 TC 25 Z9 25 U1 0 U2 4 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1553-734X J9 PLOS COMPUT BIOL JI PLoS Comput. Biol. PD JAN PY 2012 VL 8 IS 1 AR e1002337 DI 10.1371/journal.pcbi.1002337 PG 15 WC Biochemical Research Methods; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Mathematical & Computational Biology GA 891LI UT WOS:000300218100018 PM 22241976 ER PT S AU Farkas, MH Grant, GR Pierce, EA AF Farkas, Michael H. Grant, Greg R. Pierce, Eric A. BE LaVail, MM Ash, JD Anderson, RE Hollyfield, JG Grimm, C TI Transcriptome Analyses to Investigate the Pathogenesis of RNA Splicing Factor Retinitis Pigmentosa SO RETINAL DEGENERATIVE DISEASES SE Advances in Experimental Medicine and Biology LA English DT Article; Book Chapter DE RNA-seq; Next-generation sequencing; Retinitis pigmentosa; RNA splicing factors; Prpf; Transcriptome ID SEQUENCING TECHNOLOGIES; PREVALENCE; ALIGNMENT; GENE; GENOME; CELLS; TOOL C1 [Farkas, Michael H.; Pierce, Eric A.] Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Berman Gund Lab, Ocular Genom Inst, Boston, MA 02114 USA. [Grant, Greg R.] Univ Penn, Penn Ctr Bioinformat, Philadelphia, PA 19104 USA. RP Pierce, EA (reprint author), Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Berman Gund Lab, Ocular Genom Inst, 243 Charles St, Boston, MA 02114 USA. EM mfarkas@mail.med.upenn.edu; ggrant@grant.org; eric_pierce@meei.harvard.edu OI Pierce, Eric/0000-0002-2354-4102 FU NEI NIH HHS [R01 EY020902] NR 28 TC 4 Z9 4 U1 1 U2 9 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0065-2598 BN 978-1-4614-0630-3 J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 2012 VL 723 BP 519 EP 525 DI 10.1007/978-1-4614-0631-0_65 D2 10.1007/978-1-4614-0631-0 PG 7 WC Biology; Medicine, Research & Experimental; Ophthalmology SC Life Sciences & Biomedicine - Other Topics; Research & Experimental Medicine; Ophthalmology GA BYQ08 UT WOS:000299709700065 PM 22183372 ER PT J AU Masland, RH AF Masland, Richard H. TI The tasks of amacrine cells SO VISUAL NEUROSCIENCE LA English DT Article DE Retina; Neuron; Stratification; Ganglion; Types; Review ID RETINAL GANGLION-CELLS; RABBIT RETINA; MOUSE RETINA; DOPAMINERGIC-NEURONS; ELECTRON-MICROSCOPY; CAT RETINA; PA1 CELLS; Y-CELLS; ACETYLCHOLINE; INHIBITION AB Their unique patterns of size, numbers, and stratification indicate that amacrine cells have diverse functions. These are mostly unknown, as studies using imaging and electrophysiological methods have only recently begun. However, some of the events that occur within the amacrine cell population and some important unresolved puzzles can be stated purely from structural reasoning. C1 Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. RP Masland, RH (reprint author), Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, 243 Charles St,5th Floor, Boston, MA 02114 USA. EM richard_masland@meei.harvard.edu FU NIH [RO1 017169] FX Supported by NIH grant RO1 017169. R.H.M. is a Senior Investigator of Research to Prevent Blindness. I thank Michael Becker for help with the figures and the members of the Jakobs-Masland lab for reading the manuscript. NR 66 TC 33 Z9 33 U1 0 U2 15 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 0952-5238 J9 VISUAL NEUROSCI JI Visual Neurosci. PD JAN PY 2012 VL 29 IS 1 BP 3 EP 9 DI 10.1017/S0952523811000344 PG 7 WC Neurosciences; Ophthalmology SC Neurosciences & Neurology; Ophthalmology GA 895TM UT WOS:000300519300002 PM 22416289 ER PT J AU Eisen, SV Schultz, MR Vogt, D Glickman, ME Elwy, AR Drainoni, ML Osei-Bonsu, PE Martin, J AF Eisen, Susan V. Schultz, Mark R. Vogt, Dawne Glickman, Mark E. Elwy, A. Rani Drainoni, Mari-Lynn Osei-Bonsu, Princess E. Martin, James TI Mental and Physical Health Status and Alcohol and Drug Use Following Return From Deployment to Iraq or Afghanistan SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article ID POSTTRAUMATIC-STRESS-DISORDER; WAR VETERANS; MILITARY PERSONNEL; GENDER-DIFFERENCES; COMBAT DEPLOYMENT; OEF/OIF VETERANS; SCREENING-TEST; SYMPTOMS; PTSD; SOLDIERS AB Objectives. We examined (1) mental and physical health symptoms and functioning in US veterans within 1 year of returning from deployment, and (2) differences by gender, service component (Active, National Guard, other Reserve), service branch (Army, Navy, Air Force, Marines), and deployment operation (Operation Enduring Freedom/Operation Iraqi Freedom [OEF/OIF]). Methods. We surveyed a national sample of 596 OEF/OIF veterans, over-sampling women to make up 50% of the total, and National Guard and Reserve components to each make up 25%. Weights were applied to account for stratification and nonresponse bias. Results. Mental health functioning was significantly worse compared with the general population; 13.9% screened positive for probable posttraumatic stress disorder, 39% for probable alcohol abuse, and 3% for probable drug abuse. Men reported more alcohol and drug use than did women, but there were no gender differences in posttraumatic stress disorder or other mental health domains. OIF veterans reported more depression or functioning problems and alcohol and drug use than did OEF veterans. Army and Marine veterans reported worse mental and physical health than did Air Force or Navy veterans. Conclusions. Continuing identification of veterans at risk for mental health and substance use problems is important for evidence-based interventions intended to increase resilience and enhance treatment. (Am J Public Health. 2012;102:S66-S73. doi:10.2105/AJPH.2011.300609) C1 [Eisen, Susan V.; Schultz, Mark R.; Glickman, Mark E.; Elwy, A. Rani; Drainoni, Mari-Lynn; Osei-Bonsu, Princess E.] Edith Nourse Rogers Mem Vet Hosp, CHQOER, Bedford, MA 01730 USA. [Eisen, Susan V.; Glickman, Mark E.; Elwy, A. Rani; Drainoni, Mari-Lynn; Osei-Bonsu, Princess E.] Boston Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA USA. [Vogt, Dawne] VA Boston Healthcare Syst, Natl Ctr PTSD, Womens Hlth Sci Div, Boston, MA USA. [Martin, James] Bryn Mawr Coll, Bryn Mawr, PA 19010 USA. [Vogt, Dawne] Boston Univ, Sch Med, Div Psychiat, Boston, MA 02118 USA. RP Eisen, SV (reprint author), Edith Nourse Rogers Mem Vet Hosp, CHQOER, 200 Springs Rd,152, Bedford, MA 01730 USA. EM Susan.Eisen@va.gov OI Glickman, Mark/0000-0003-3993-2801 FU Veterans Administration Health Services Research and Development (HSRD) [IAC 06-259-2]; Center for Health Quality, Outcomes & Economic Research, VA HSR&D Center of Excellence; Women's Health Sciences Division, National Center for PTSD, VA Boston Healthcare System FX This research was funded by the Veterans Administration Health Services Research and Development (HSR & D; grant IAC 06-259-2; S. V. Eisen, PI), by the Center for Health Quality, Outcomes & Economic Research, a VA HSR&D Center of Excellence, and by Women's Health Sciences Division, National Center for PTSD, VA Boston Healthcare System. NR 52 TC 50 Z9 50 U1 3 U2 27 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 800 I STREET, NW, WASHINGTON, DC 20001-3710 USA SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PY 2012 VL 102 SU 1 BP S66 EP S73 DI 10.2105/AJPH.2011.300609 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 893EO UT WOS:000300338600021 PM 22390605 ER PT J AU Katz, IR McCarthy, JF Ignacio, RV Kemp, J AF Katz, Ira R. McCarthy, John F. Ignacio, Rosalinda V. Kemp, Janet TI Suicide Among Veterans in 16 States, 2005 to 2008: Comparisons Between Utilizers and Nonutilizers of Veterans Health Administration (VHA) Services Based on Data From the National Death Index, the National Violent Death Reporting System, and VHA Administrative Records SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article ID MILITARY SERVICE; FIREARM SUICIDE; US VETERANS; RISK; CARE; POPULATION; MORTALITY; AFFAIRS; DEPRESSION; PATIENT AB Objectives. We sought to compare suicide rates among veterans utilizing Veterans Health Administration (VHA) services versus those who did not. Methods. Suicide rates from 2005 to 2008 were estimated for veterans in the 16 states that fully participated in the National Violent Death Reporting System (NVDRS), using data from the National Death Index, NVDRS, and VHA records. Results. Between 2005 and 2008, veteran suicide rates differed by age and VHA utilization status. Among men aged 30 years and older, suicide rates were consistently higher among VHA utilizers. However, among men younger than 30 years, rates declined significantly among VHA utilizers while increasing among nonutilizers. Over these years, an increasing proportion of male veterans younger than 30 years received VHA services, and these individuals had a rising prevalence of diagnosed mental health conditions. Conclusions. The higher rates of suicide for utilizers of VHA among veteran men aged 30 and older were consistent with previous reports about which veterans utilize VHA services. The increasing rates of mental health conditions in utilizers younger than 30 years suggested that the decreasing relative rates in this group were related to the care provided, rather than to selective enrollment of those at lower risk for suicide. (Am J Public Health. 2012;102:S105-S110. doi: 10.2105/AJPH.2011.300503) C1 [Katz, Ira R.; McCarthy, John F.; Ignacio, Rosalinda V.; Kemp, Janet] US Dept Vet Affairs, Washington, DC USA. [Katz, Ira R.; McCarthy, John F.; Ignacio, Rosalinda V.] VA Off Mental Hlth Operat, Richmond, VA 23219 USA. RP McCarthy, JF (reprint author), VA Serious Mental Illness Treatment Resource & Ev, Bldg 14,Room D0129,2800 Plymouth Rd, Ann Arbor, MI 48109 USA. EM John.McCarthy2@VA.gov FU VA Office of Mental Health Services FX This study was funded by the VA Office of Mental Health Services. NR 39 TC 20 Z9 20 U1 2 U2 12 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 800 I STREET, NW, WASHINGTON, DC 20001-3710 USA SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PY 2012 VL 102 SU 1 BP S105 EP S110 DI 10.2105/AJPH.2011.300503 PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 893EO UT WOS:000300338600027 PM 22390582 ER PT J AU Magruder, KM Yeager, D Brawman-Mintzer, O AF Magruder, Kathyrn M. Yeager, Derik Brawman-Mintzer, Olga TI The Role of Pain, Functioning, and Mental Health in Suicidality Among Veterans Affairs Primary Care Patients SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article ID POSTTRAUMATIC-STRESS-DISORDER; NEUROPSYCHIATRIC INTERVIEW MINI; RELIABILITY; VALIDITY; RISK; COMORBIDITY; POPULATION; PREVALENCE; ADULTS; SF-36 AB Objectives. We examined suicidality, pain, functioning, and psychiatric disorders among veterans in primary care by using both self-report and clinical measures of pain and mental health to determine correlates that might be clinically useful in primary care settings. Methods. Data were from 884 Veterans Affairs patients enrolled in a regional 4-site cross-sectional study. Patients were administered measures that assessed functioning (including pain) and psychiatric disorders. Data were merged with medical records for clinical pain indicators. Results. Overall, 9.1% (74 of 816) of patients indicated suicidal ideation, with those who were middle-aged, unemployed because of disability, had less than college education, and served in a warzone most likely to consider suicidality. Suicidal patients had worse functioning (measured by the Short Form-36) than did nonsuicidal patients in every domain, including bodily pain, and were more likely to meet criteria for a psychiatric diagnosis. However, when pain and mental health were jointly considered, only mental health (both psychiatric diagnosis and mental health functioning) was related to suicidality. Conclusions. Although providers should be alert to the possibility of suicidality in patients with pain, they should be vigilant when patients have a psychiatric disorder or poor mental health. (Am J Public Health. 2012;102:S118-S124. doi:10.2105/AJPH.2011.300451) C1 [Magruder, Kathyrn M.; Yeager, Derik; Brawman-Mintzer, Olga] Ralph H Johnson VA Med Ctr, Mental Hlth Serv Line, Charleston, SC 29401 USA. [Magruder, Kathyrn M.] Med Univ S Carolina, Dept Psychiat & Behav Sci, Mil Sci Div, Dept Med,Biostat & Epidemiol Div, Charleston, SC USA. RP Yeager, D (reprint author), Ralph H Johnson VA Med Ctr, Mental Hlth Serv Line, 109 Bee St, Charleston, SC 29401 USA. EM yeagerde@musc.edu FU Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Health Services Research and Development [VCR 99-010-2, SHP 08-160] FX This article is based upon work supported by the Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Health Services Research and Development (VCR 99-010-2 and SHP 08-160). NR 30 TC 9 Z9 9 U1 1 U2 5 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 800 I STREET, NW, WASHINGTON, DC 20001-3710 USA SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PY 2012 VL 102 SU 1 BP S118 EP S124 DI 10.2105/AJPH.2011.300451 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 893EO UT WOS:000300338600029 PM 22390584 ER PT J AU Miller, M Azrael, D Barber, C Mukamal, K Lawler, E AF Miller, Matthew Azrael, Deborah Barber, Catherine Mukamal, Kenneth Lawler, Elizabeth TI A Call to Link Data to Answer Pressing Questions About Suicide Risk Among Veterans SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Editorial Material ID PERSIAN-GULF-WAR; US VETERANS; MORTALITY C1 [Miller, Matthew] Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Harvard Injury Control Res Ctr, Boston, MA 02115 USA. [Mukamal, Kenneth] Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA 02215 USA. [Lawler, Elizabeth] VA Boston Healthcare Syst, VA Cooperat Studies Program, Massachusetts Vet Epidemiol Res & Informat Ctr, Boston, MA USA. [Lawler, Elizabeth] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Aging, Boston, MA 02115 USA. RP Miller, M (reprint author), Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Harvard Injury Control Res Ctr, 677 Huntington Ave,Kresge 305, Boston, MA 02115 USA. EM mmiller@hsph.harvard.edu NR 10 TC 9 Z9 9 U1 0 U2 4 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 800 I STREET, NW, WASHINGTON, DC 20001-3710 USA SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PY 2012 VL 102 SU 1 BP S20 EP + DI 10.2105/AJPH.2011.300572 PG 2 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 893EO UT WOS:000300338600010 PM 22390593 ER PT S AU Lee, JH Bacskai, BJ Ayata, C AF Lee, Jeong Hyun Bacskai, Brian J. Ayata, Cenk BE Conn, PM TI Genetic Animal Models of Cerebral Vasculopathies SO ANIMAL MODELS OF MOLECULAR PATHOLOGY SE Progress in Molecular Biology and Translational Science LA English DT Review; Book Chapter ID AMYLOID PRECURSOR PROTEIN; AUTOSOMAL-DOMINANT ARTERIOPATHY; SMOOTH-MUSCLE-CELLS; TRANSGENIC MOUSE MODEL; INSULIN-DEGRADING ENZYME; WHITE-MATTER HYPERINTENSITIES; FAMILIAL ALZHEIMERS-DISEASE; LONG-TERM POTENTIATION; SMALL-VESSEL-DISEASE; BLOOD-BRAIN-BARRIER C1 [Lee, Jeong Hyun; Ayata, Cenk] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol,Neurovasc Res Lab, Charlestown, MA USA. [Bacskai, Brian J.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol,MassGen Inst Neurodegenerat Dis, Charlestown, MA USA. [Ayata, Cenk] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Neurosci Intens Care Unit,Dept Neurol, Charlestown, MA USA. [Ayata, Cenk] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Stroke Serv,Dept Neurol, Charlestown, MA USA. RP Lee, JH (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol,Neurovasc Res Lab, Charlestown, MA USA. OI Lee, Jeong Hyun/0000-0003-0504-0119 FU NCRR NIH HHS [UL1 RR 025758, UL1 RR025758]; NIA NIH HHS [AG021084, R01 AG021084]; NIBIB NIH HHS [R01 EB000768]; NINDS NIH HHS [NS055104, NS061505, P01 NS055104, R01 NS061505] NR 197 TC 8 Z9 8 U1 0 U2 7 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 1877-1173 BN 978-0-12-394596-9 J9 PROG MOL BIOL TRANSL JI Prog. Molec. Biol. Transl. Sci. PY 2012 VL 105 BP 25 EP 55 DI 10.1016/B978-0-12-394596-9.00002-0 PG 31 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BYN14 UT WOS:000299397700002 PM 22137428 ER PT S AU Mizoguchi, A AF Mizoguchi, Atsushi BE Conn, PM TI Animal Models of Inflammatory Bowel Disease SO ANIMAL MODELS OF MOLECULAR PATHOLOGY SE Progress in Molecular Biology and Translational Science LA English DT Review; Book Chapter ID T-CELL-RECEPTOR; ALPHA MUTANT MICE; CHRONIC INTESTINAL INFLAMMATION; HAPTEN-INDUCED COLITIS; ALDRICH-SYNDROME PROTEIN; TUMOR-NECROSIS-FACTOR; TNBS-INDUCED COLITIS; GROWTH-FACTOR-BETA; NF-KAPPA-B; ESTABLISHED EXPERIMENTAL COLITIS C1 Harvard Univ, Sch Med, Dept Pathol,Massachusetts Gen Hosp, Mol Pathol Unit,Ctr Study Inflammatory Bowel Dis, Boston, MA 02115 USA. RP Mizoguchi, A (reprint author), Harvard Univ, Sch Med, Dept Pathol,Massachusetts Gen Hosp, Mol Pathol Unit,Ctr Study Inflammatory Bowel Dis, Boston, MA 02115 USA. FU NIAID NIH HHS [R01 AI081807, R01AI081807]; NIDDK NIH HHS [RC1DK086242] NR 246 TC 61 Z9 62 U1 4 U2 27 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 1877-1173 BN 978-0-12-394596-9 J9 PROG MOL BIOL TRANSL JI Prog. Molec. Biol. Transl. Sci. PY 2012 VL 105 BP 263 EP 320 DI 10.1016/B978-0-12-394596-9.00009-3 PG 58 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BYN14 UT WOS:000299397700009 PM 22137435 ER PT S AU Smith, GP AF Smith, Gideon P. BE Conn, PM TI Animal Models of Cutaneous and Hepatic Fibrosis SO ANIMAL MODELS OF MOLECULAR PATHOLOGY SE Progress in Molecular Biology and Translational Science LA English DT Review; Book Chapter ID GROWTH-FACTOR-BETA; TUMOR-NECROSIS-FACTOR; C VIRUS-INFECTION; EXPERIMENTAL AUTOIMMUNE HEPATITIS; BLEOMYCIN-INDUCED SCLERODERMA; STELLATE CELL ACTIVATION; MITOCHONDRIAL TRIFUNCTIONAL PROTEIN; SYSTEMIC-SCLEROSIS SCLERODERMA; COLLAGEN GENE-EXPRESSION; RENIN-ANGIOTENSIN SYSTEM C1 Harvard Univ, Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02115 USA. RP Smith, GP (reprint author), Harvard Univ, Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02115 USA. NR 217 TC 4 Z9 4 U1 0 U2 7 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 1877-1173 BN 978-0-12-394596-9 J9 PROG MOL BIOL TRANSL JI Prog. Molec. Biol. Transl. Sci. PY 2012 VL 105 BP 371 EP 409 DI 10.1016/B978-0-12-394596-9.00011-1 PG 39 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BYN14 UT WOS:000299397700011 PM 22137437 ER PT J AU Graziotto, JJ Cao, K Collins, FS Krainc, D AF Graziotto, John J. Cao, Kan Collins, Francis S. Krainc, Dimitri TI Rapamycin activates autophagy in Hutchinson-Gilford progeria syndrome Implications for normal aging and age-dependent neurodegenerative disorders SO AUTOPHAGY LA English DT Editorial Material DE progerin; rapamycin; autophagy; aging; neurodegeneration; progeria ID GENETICALLY HETEROGENEOUS MICE; AGGREGATE-PRONE PROTEINS; EXTENDS LIFE-SPAN; MOUSE MODEL; DEFICIENT MICE; POLYGLUTAMINE EXPANSIONS; TELOMERE DYSFUNCTION; CELLULAR SENESCENCE; HUNTINGTONS-DISEASE; MUTANT HUNTINGTIN AB While rapamycin has been in use for years in transplant patients as an antirejection drug, more recently it has shown promise in treating diseases of aging, such as neurodegenerative disorders and atherosclerosis. We recently reported that rapamycin reverses the cellular phenotype of fibroblasts from children with the premature aging disease Hutchinson-Gilford progeria syndrome (HGPS). We found that the causative aberrant protein, progerin, was cleared through autophagic mechanisms when the cells were treated with rapamycin, suggesting a new potential treatment for HGPS. Recent evidence shows that progerin is also present in aged tissues of healthy individuals, suggesting that progerin may contribute to physiological aging. While it is intriguing to speculate that rapamycin may affect normal aging in humans, as it does in lower organisms, it will be important to identify safer analogs of rapamycin for chronic treatments in humans in order to minimize toxicity. In addition to its role in HGPS and normal aging, we discuss the potential of rapamycin for the treatment of age-dependent neurodegenerative diseases. C1 [Graziotto, John J.; Krainc, Dimitri] Harvard Univ, Sch Med, MassGen Inst Neurodegenerat Dis, Dept Neurol,Massachusetts Gen Hosp, Charlestown, MA USA. [Cao, Kan] Univ Maryland, Dept Cell Biol & Mol Genet, College Pk, MD 20742 USA. [Collins, Francis S.] NHGRI, Genome Technol Branch, NIH, Bethesda, MD 20892 USA. RP Krainc, D (reprint author), Harvard Univ, Sch Med, MassGen Inst Neurodegenerat Dis, Dept Neurol,Massachusetts Gen Hosp, Charlestown, MA USA. EM krainc@helix.mgh.harvard.edu FU NIA NIH HHS [R00 AG029761] NR 56 TC 25 Z9 30 U1 2 U2 11 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 1554-8627 J9 AUTOPHAGY JI Autophagy PD JAN PY 2012 VL 8 IS 1 BP 147 EP 151 DI 10.4161/auto.8.1.18331 PG 5 WC Cell Biology SC Cell Biology GA 892ZR UT WOS:000300325000021 PM 22170152 ER PT J AU Furin, J Gegia, M Mitnick, C Rich, M Shin, S Becerra, M Drobac, P Farmer, P Hurtado, R Joseph, JK Keshavjee, S Kalandadze, I AF Furin, Jennifer Gegia, Medea Mitnick, Carole Rich, Michael Shin, Sonya Becerra, Mercedes Drobac, Peter Farmer, Paul Hurtado, Rocio Joseph, J. Keith Keshavjee, Salmaan Kalandadze, Iagor TI Eliminating the category II retreatment regimen from national tuberculosis programme guidelines: the Georgian experience SO BULLETIN OF THE WORLD HEALTH ORGANIZATION LA English DT Article AB Problem The category II retreatment regimen for management of tuberculosis in previously treated patients was first introduced in the early 1990s. It consists of 8 months of total therapy with the addition of streptomycin to standard first-line medications. A review of 6500 patients on category II therapy in Georgia showed poor outcomes and high rates of streptomycin resistance. Approach The National Tuberculosis Program used an evidence-based analysis of national data to convince policy-makers that category II therapy should be eliminated from national guidelines in Georgia. Local setting The World Health Organization tuberculosis case-notification rate in Georgia is 102 per 100000 population. All patients receive culture and drug susceptibility testing as a standard part of tuberculosis diagnosis. In 2009, routine surveillance found multidrug-resistant tuberculosis in 10.6% of newly diagnosed patients and 32.5% of previously treated cases. Relevant changes Category II retreatment regimen is no longer used in Georgia. Treatment is guided by results of drug susceptibility testing - using rapid, molecular tests where possible - for all previously treated tuberculosis patients. Lessons learnt There was little resistance to policy change because the review was initiated and led by the National Tuberculosis Program. This experience can serve as a successful model for other countries to make informed decisions about the use of category II therapy. C1 [Furin, Jennifer] Case Western Reserve Univ, Sch Med, Cleveland, OH 44106 USA. [Gegia, Medea; Kalandadze, Iagor] Natl Ctr TB & Lung Dis, Tbilisi, Rep of Georgia. [Mitnick, Carole; Becerra, Mercedes] Harvard Univ, Sch Med, Boston, MA USA. [Rich, Michael; Drobac, Peter; Farmer, Paul; Joseph, J. Keith] Partners Hlth, Boston, MA USA. [Shin, Sonya; Keshavjee, Salmaan] Brigham & Womens Hosp, Boston, MA 02115 USA. [Hurtado, Rocio] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Furin, J (reprint author), Case Western Reserve Univ, Sch Med, 10900 Euclid Ave, Cleveland, OH 44106 USA. EM jenniferfurin@gmail.com NR 9 TC 12 Z9 12 U1 0 U2 3 PU WORLD HEALTH ORGANIZATION PI GENEVA 27 PA MARKETING AND DISSEMINATION, CH-1211 GENEVA 27, SWITZERLAND SN 0042-9686 J9 B WORLD HEALTH ORGAN JI Bull. World Health Organ. PD JAN PY 2012 VL 90 IS 1 BP 63 EP 66 DI 10.2471/BLT.11.092320 PG 4 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 887FZ UT WOS:000299913600024 PM 22271966 ER PT J AU Gerstner, ER Batchelor, TT AF Gerstner, Elizabeth R. Batchelor, Tracy T. TI Antiangiogenic Therapy for Glioblastoma SO CANCER JOURNAL LA English DT Review DE Antiangiogenic therapy; treatment; VEGF; small molecule inhibitors; antibodies; glioblastoma ID ENDOTHELIAL GROWTH-FACTOR; BEVACIZUMAB PLUS IRINOTECAN; TYROSINE KINASE INHIBITOR; MALIGNANT GLIOMA-CELLS; RECURRENT GLIOBLASTOMA; TUMOR ANGIOGENESIS; VEGF-TRAP; IN-VIVO; RADIATION NECROSIS; CLINICAL-TRIALS AB Glioblastomas are among the most vascular tumors due to the expression of a variety of proangiogenic factors. New drug regimens are being developed to target angiogenesis in an attempt to arrest tumor growth. In particular, the vascular endothelial growth factor (VEGF) pathway has been a prime drug target. Preliminary results with anti-VEGF agents have been promising with prolonged progression-free survival reported. In addition, the antipermeability effects of anti-VEGF agents have important consequences for tumor imaging and for patient quality of life by decreasing corticosteroid dependence. Unfortunately, the response to anti-VEGF therapy is transient, and the majority of patients eventually relapsed, so more work is needed to understand the mechanisms of tumor escape. C1 [Gerstner, Elizabeth R.] Massachusetts Gen Hosp, Ctr Canc, Stephen E & Catherine Pappas Ctr Neurooncol, Dept Neurol, Boston, MA 02114 USA. [Gerstner, Elizabeth R.; Batchelor, Tracy T.] Massachusetts Gen Hosp, Ctr Canc, Dept Radiat Oncol, Boston, MA 02114 USA. [Batchelor, Tracy T.] Massachusetts Gen Hosp, Ctr Canc, Div Hematol & Oncol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Gerstner, ER (reprint author), Massachusetts Gen Hosp, Ctr Canc, Stephen E & Catherine Pappas Ctr Neurooncol, Dept Neurol, Yawkey 9E,55 Fruit St, Boston, MA 02114 USA. EM egerstner@partners.org FU Pfizer; AstraZeneca; millennium FX Dr Batchelor has received honoraria from Merck, Roche, Spectrum, and Millennium. He has also received grants from Pfizer, AstraZeneca, and millennium. For the remaining authors none were declared. NR 53 TC 28 Z9 31 U1 1 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1528-9117 EI 1540-336X J9 CANCER J JI Cancer J. PD JAN-FEB PY 2012 VL 18 IS 1 BP 45 EP 50 DI 10.1097/PPO.0b013e3182431c6f PG 6 WC Oncology SC Oncology GA 892RZ UT WOS:000300304600009 PM 22290257 ER PT J AU Figueroa, AL Subramanian, SS Cury, RC Truong, QA Gardecki, JA Tearney, GJ Hoffmann, U Brady, TJ Tawakol, A AF Figueroa, Amparo L. Subramanian, Sharath S. Cury, Ricardo C. Truong, Quynh A. Gardecki, Joseph A. Tearney, Guillermo J. Hoffmann, Udo Brady, Thomas J. Tawakol, Ahmed TI Distribution of Inflammation Within Carotid Atherosclerotic Plaques With High-Risk Morphological Features A Comparison Between Positron Emission Tomography Activity, Plaque Morphology, and Histopathology SO CIRCULATION-CARDIOVASCULAR IMAGING LA English DT Article DE atherosclerosis; carotid arteries; imaging; morphogenesis ID SURFACE-MORPHOLOGY; CORONARY SYNDROMES; ISCHEMIC-STROKE; CT ANGIOGRAPHY; OXFORD PLAQUE; ARTERY; FLUORODEOXYGLUCOSE; STENOSIS; MACROPHAGES; ULTRASOUND AB Background-Several high-risk morphological features (HRM) of plaques, especially in combination, are associated with an increased risk of a clinical event. Although plaque inflammation is also associated with atherothrombosis, the relationship between inflammation and number of HRM is not well understood. Methods and Results-Thirty-four patients underwent (18)flurodeoxyglucose positron emission tomography (FDG-PET) imaging, and carotid atherosclerotic inflammation was assessed (target-to-background ratio). Additionally, in a subset of 10 subjects with carotid stenosis who underwent carotid endarterectomy, inflammation was histologically assessed (CD68 staining). Vessel wall morphology was examined using computed tomography for the presence of visible plaque and presence of 3 HRM: positive remodeling, luminal irregularity, and low attenuation. A total of 100 vascular segments were analyzed, of which 69 contained visible plaque (26 plaques with >= 1 HRM). Inflammation, by FDG uptake (target-to-background ratio), was higher in plaques with (versus without) HRM (mean +/- SEM: 2.21 +/- 0.20 versus 1.66 +/- 0.07, P=0.0003) and increased with the number of HRM observed (P<0.001 for trend). Similarly, inflammation within atherosclerotic specimens (% CD68 staining) was higher in plaques with (versus without) HRM (median [interquartile range]: 10 [0, 19.85] versus 0 [0, 1.55], P=0.01) and increased with the number of HRM observed (P<0.001 for trend). Conclusions-Inflammation, as assessed by both FDG uptake and histology, is increased in plaques containing HRM and increases with increasing number of HRM. These data support the concept that inflammation accumulates relative to the burden of morphological abnormalities. (Circ Cardiovasc Imaging. 2012;5:69-77.) C1 [Figueroa, Amparo L.; Subramanian, Sharath S.; Cury, Ricardo C.; Truong, Quynh A.; Hoffmann, Udo; Brady, Thomas J.; Tawakol, Ahmed] Massachusetts Gen Hosp, Cardiac MR PET CT Program, Dept Radiol, Boston, MA 02114 USA. [Figueroa, Amparo L.; Subramanian, Sharath S.; Cury, Ricardo C.; Truong, Quynh A.; Hoffmann, Udo; Brady, Thomas J.; Tawakol, Ahmed] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Figueroa, Amparo L.; Subramanian, Sharath S.; Cury, Ricardo C.; Truong, Quynh A.; Gardecki, Joseph A.; Tearney, Guillermo J.; Hoffmann, Udo; Brady, Thomas J.; Tawakol, Ahmed] Harvard Univ, Sch Med, Boston, MA USA. [Figueroa, Amparo L.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Cury, Ricardo C.] Baptist Cardiac & Vasc Inst, Miami, FL USA. [Truong, Quynh A.; Tawakol, Ahmed] Massachusetts Gen Hosp, Dept Med, Div Cardiol, Boston, MA 02114 USA. [Gardecki, Joseph A.] Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA. [Tearney, Guillermo J.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Tearney, Guillermo J.] Harvard MIT Hlth Sci & Technol, Cambridge, MA USA. [Gardecki, Joseph A.; Tearney, Guillermo J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Ctr Photomed, Boston, MA USA. RP Tawakol, A (reprint author), Massachusetts Gen Hosp, Cardiac MR PET CT Program, Dept Radiol, 165 Cambridge St,Suite 400, Boston, MA 02114 USA. EM atawakol@partners.org FU CIMIT (Center for the Integration of Medicine and Innovative Technologies); [NIH/R01 HL095123-01] FX Dr Tawakol was funded by NIH/R01 HL095123-01 and CIMIT (Center for the Integration of Medicine and Innovative Technologies). NR 39 TC 57 Z9 59 U1 2 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1941-9651 J9 CIRC-CARDIOVASC IMAG JI Circ.-Cardiovasc. Imaging PD JAN PY 2012 VL 5 IS 1 BP 69 EP 77 DI 10.1161/CIRCIMAGING.110.959478 PG 9 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA 894HG UT WOS:000300417100012 PM 22038986 ER PT J AU Truong, QA Massaro, JM Rogers, IS Mahabadi, AA Kriegel, MF Fox, CS O'Donnell, CJ Hoffmann, U AF Truong, Quynh A. Massaro, Joseph M. Rogers, Ian S. Mahabadi, Amir A. Kriegel, Matthias F. Fox, Caroline S. O'Donnell, Christopher J. Hoffmann, Udo TI Reference Values for Normal Pulmonary Artery Dimensions by Noncontrast Cardiac Computed Tomography The Framingham Heart Study SO CIRCULATION-CARDIOVASCULAR IMAGING LA English DT Article DE pulmonary artery; Framingham Heart Study; computed tomography ID HYPERTENSION; CT; DIAMETER; QUANTIFICATION; LUNG AB Background-Main pulmonary artery diameter (mPA) and ratio of mPA to ascending aorta diameter (ratio PA) derived from chest CT are commonly reported in clinical practice. We determined the age-and sex-specific distribution and normal reference values for mPA and ratio PA by CT in an asymptomatic community-based population. Methods and Results-In 3171 men and women (mean age, 51 +/- 10 years; 51% men) from the Framingham Heart Study, a noncontrast, ECG-gated, 8-slice cardiac multidetector CT was performed. We measured the mPA and transverse axial diameter of the ascending aorta at the level of the bifurcation of the right pulmonary artery and calculated the ratio PA. We defined the healthy referent cohort (n=706) as those without obesity, hypertension, current and past smokers, chronic obstructive pulmonary disease, history of pulmonary embolism, diabetics, cardiovascular disease, and heart valve surgery. The mean mPA diameter in the overall cohort was 25.1 +/- 2.8 mm and mean ratio PA was 0.77 +/- 0.09. The sex-specific 90th percentile cutoff value for mPA diameter was 28.9 mm in men and 26.9 mm in women and was associated with increase risk for self-reported dyspnea (adjusted odds ratio, 1.31; P=0.02). The 90th percentile cutoff value for ratio PA of the healthy referent group was 0.91, similar between sexes but decreased with increasing age (range, 0.82-0.94), though not associated with dyspnea. Conclusions-For simplicity, we established 29 mm in men and 27 mm in women as sex-specific normative reference values for mPA and 0.9 for ratio PA. (Circ Cardiovasc Imaging. 2012;5:147-154.) C1 [Truong, Quynh A.] Harvard Univ, Massachusetts Gen Hosp, Div Cardiol, Cardiac MR PET CT Program,Med Sch,Div Cardiol, Boston, MA 02114 USA. [Massaro, Joseph M.] Boston Univ, Dept Math, Boston, MA 02215 USA. [Rogers, Ian S.] Stanford Univ, Div Cardiovasc Med, Sch Med, Stanford, CA 94305 USA. [Mahabadi, Amir A.] Univ Clin Essen, W German Heart Ctr, Dept Cardiol, Essen, Germany. [Fox, Caroline S.; O'Donnell, Christopher J.] NHLBI, Framingham Heart Study, Framingham, MA USA. RP Truong, QA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Div Cardiol, Cardiac MR PET CT Program,Med Sch,Div Cardiol, 165 Cambridge St,Suite 400, Boston, MA 02114 USA. EM qtruong@partners.org OI Massaro, Joseph/0000-0002-2682-4812 FU National Heart, Lung, and Blood Institute [N01-HC-25195]; National Institutes of Health [T32HL076136, K23HL098370, L30HL093896] FX The Framingham Heart Study is supported by the National Heart, Lung, and Blood Institute (N01-HC-25195). Drs Truong and Rogers received support from National Institutes of Health grant T32HL076136. Dr. Truong also received support from National Institutes of Health grant K23HL098370 and L30HL093896. NR 20 TC 46 Z9 49 U1 0 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1941-9651 J9 CIRC-CARDIOVASC IMAG JI Circ.-Cardiovasc. Imaging PD JAN PY 2012 VL 5 IS 1 BP 147 EP 154 DI 10.1161/CIRCIMAGING.111.968610 PG 8 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA 894HG UT WOS:000300417100021 PM 22178898 ER PT J AU Sedaghat, AR Anderson, ICW McGinley, BM Rossberg, MI Redett, RJ Ishman, SL AF Sedaghat, Ahmad R. Anderson, Iee Ching W. McGinley, Brian M. Rossberg, Mark I. Redett, Richard J. Ishman, Stacey L. TI Characterization of Obstructive Sleep Apnea Before and After Tongue-Lip Adhesion in Children With Micrognathia SO CLEFT PALATE-CRANIOFACIAL JOURNAL LA English DT Article; Proceedings Paper CT 66th Annual Meeting of the American-Cleft-Palate-Craniofacial-Association (ACPA) on Flood, Disaster and Turmoil - Preserving the Continuity of Team Care When a Community Is in Crisis CY APR 20-25, 2009 CL Scottsdale, AZ SP Amer Cleft Palate Craniofacial Assoc (ACPA) DE micrognathia; OSA; Pierre Robin; tongue-lip adhesion ID ISOLATED ROBIN,PIERRE SEQUENCE; PIERRE ROBIN-SEQUENCE; AIRWAY MANAGEMENT; MANDIBULAR DISTRACTION; INFANCY AB Objectives: To characterize airway obstruction before and after tongue-lip adhesion in children with micrognathia using polysomnography. Design: Retrospective pilot case series. Participants and Methods: Evaluation of all children with micrognathia who underwent tongue-lip adhesion and polysomnography before and after surgery from 2002 to 2007 (N = 8). Results: Eight children met inclusion criteria; six were girls. The mean interval between polysomnography and tongue-lip adhesion was 6 days (range, 2 to 13 days) preoperatively and 17 days (range, 5 to 32 days) postoperatively. Severe obstructive sleep apnea was identified in seven of eight (88%) children, with a mean preoperative obstructive apnea hypopnea index of 52.6 events per hour (range, 7.1 to 85.7 events per hour). None had significant central sleep apneas (>5 per hour). Tongue-lip adhesion resulted in a mean decrease of 34.5 events per hour (range, -65.8 to 71.6 events per hour). After tongue-lip adhesion, seven of eight (87.5%) patients had an improved obstructive apnea hypopnea index, with resolution of obstructive sleep apnea in one child and improvement to mild (two) and moderate (two) obstructive sleep apnea in four others. Only one child had an obstructive apnea hypopnea index that increased after tongue-lip adhesion. Peak end-tidal pCO(2) measurements were elevated in all eight children before surgery at a mean of 60 mm Hg (range, 52 to 76 mm Hg) that improved to 51 mm Hg (range, 45 to 59 mm Hg), with normal peak levels in four children. Oxygen saturation nadir improved from 73% (range, 58% to 81%) to 82% (range, 65% to 94%). Conclusions: Tongue-lip adhesion may be performed in micrognathic infants to alleviate airway obstruction. Polysomnographic evaluation in this pilot study before and after surgery suggests that tongue-lip adhesion usually improves obstructive sleep apnea, but only 38% had complete resolution. Future studies of tongue-lip adhesion efficacy should include polysomnographic evaluation. C1 [Ishman, Stacey L.] Johns Hopkins Sch Med, Dept Otolaryngol Head & Neck Surg, Baltimore, MD 21287 USA. [Sedaghat, Ahmad R.; Anderson, Iee Ching W.] Harvard Univ, Sch Med, Dept Otolaryngol, Massachusetts Eye & Ear Infirm, Boston, MA 02115 USA. [McGinley, Brian M.] Johns Hopkins Sch Med, Dept Pediat, Eudowood Div Pediat Pulmonol, Baltimore, MD 21287 USA. [Rossberg, Mark I.] Johns Hopkins Sch Med, Dept Anesthesiol & Crit Care Med, Baltimore, MD 21287 USA. [Redett, Richard J.] Johns Hopkins Sch Med, Dept Surg, Div Plast Surg, Baltimore, MD 21287 USA. RP Ishman, SL (reprint author), Johns Hopkins Sch Med, Dept Otolaryngol Head & Neck Surg, 601 N Caroline St,Room 6231, Baltimore, MD 21287 USA. EM sishman1@jhmi.edu OI Ishman, Stacey/0000-0003-0997-9692 NR 23 TC 16 Z9 17 U1 0 U2 1 PU ALLIANCE COMMUNICATIONS GROUP DIVISION ALLEN PRESS PI LAWRENCE PA 810 EAST 10TH STREET, LAWRENCE, KS 66044 USA SN 1545-1569 J9 CLEFT PALATE-CRAN J JI Cleft Palate-Craniofac. J. PD JAN PY 2012 VL 49 IS 1 BP 21 EP 26 DI 10.1597/10-240 PG 6 WC Dentistry, Oral Surgery & Medicine; Surgery SC Dentistry, Oral Surgery & Medicine; Surgery GA 893JQ UT WOS:000300352600004 PM 21495918 ER PT J AU Mahon, MJ AF Mahon, M. J. TI The Parathyroid Hormone Receptorsome and the Potential for Therapeutic Intervention SO CURRENT DRUG TARGETS LA English DT Review DE Parathyroid hormone 1 receptor; parathyroid hormone; G proteins; calpain; calmodulin; arrestins; NHERF-1 and-2; ezrin; osteoporosis ID (PTH)/PTH-RELATED PEPTIDE RECEPTOR; EXCHANGER REGULATORY FACTOR; OPOSSUM KIDNEY-CELLS; PROTEIN-COUPLED-RECEPTORS; CARBOXYL-TERMINAL REGION; PDZ-DOMAIN INTERACTIONS; CALPAIN SMALL-SUBUNIT; PHOSPHOLIPASE-C-BETA; OSTEOBLASTIC CELLS; CYCLIC-AMP AB The parathyroid hormone 1 receptor (PTH1R) is activated by parathyroid hormone (PTH) and parathyroid hormone related protein (PTHrP), hormones that mediate mineral ion homeostasis and tissue development, respectively. These diverse actions mediated by one receptor are likely due to the formation of cell-specific receptorsome complexes with cytosolic constituents. Through the second and third intracellular loops, the PTH1R couples to several G protein subclasses, including G(s), G(q/11), G(i/o) and G(12/13), resulting in the activation of many pathways. The PTH1R carboxy-terminal tail directs interactions with a plethora of binding partners. The WD1 and WD7 repeats of the G protein beta subunit directly bind to a novel interaction domain located near the amino-terminal end of the PTH1R carboxy-terminal tail. This G beta gamma binding site likely contributes to the promiscuous G protein coupling displayed by the PTH1R. Partially overlapping this site is an EF-hand binding domain that directs interactions with calpain, a calcium-activated protease, and calmodulin, a ubiquitous calcium sensor. A lysine-arginine-lysine motif located on the juxtamembrane region of the carboxy-terminal tail mediates interactions with ezrin, an actin-membrane cross-linking protein. The C-terminus of the PTH1R binds to the sodium-hydrogen regulatory factors (NHERFs) via a PDZ domain-mediated interaction, an association that influences signaling and membrane anchoring. Through direct interactions with ezrin and NHERF-1, a PTH1R receptorsome complex exists on apical membranes of the proximal tubule, an assembly that directs PTH-mediated regulation of phosphate transport. Targeting the PTH1R receptorsome will likely enhance therapies directed towards the treatment of osteoporosis and enhancing the hematopoietic stem cell niche. C1 [Mahon, M. J.] Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. [Mahon, M. J.] Harvard Univ, Dept Med, Sch Med, Cambridge, MA 02138 USA. RP Mahon, MJ (reprint author), Massachusetts Gen Hosp, Endocrine Unit, 50 Blossom St,Their 10, Boston, MA 02114 USA. EM mahon@helix.mgh.harvard.edu FU National Institutes of Health [P01 DK073911] FX This work was supported by a grant from the National Institutes of Health (P01 DK073911). NR 112 TC 8 Z9 8 U1 0 U2 15 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y-2, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1389-4501 J9 CURR DRUG TARGETS JI Curr. Drug Targets PD JAN PY 2012 VL 13 IS 1 BP 116 EP 128 PG 13 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 892JD UT WOS:000300281600009 PM 21777186 ER PT J AU Kurbanyan, K Hoesl, LM Schrems, WA Hamrah, P AF Kurbanyan, K. Hoesl, L. M. Schrems, W. A. Hamrah, P. TI Corneal nerve alterations in acute Acanthamoeba and fungal keratitis: an in vivo confocal microscopy study SO EYE LA English DT Article DE corneal nerves; Acanthamoeba keratitis; fungal keratitis; in vivo confocal microscopy ID MORPHOLOGY AB Purpose To study sub-basal corneal nerve alterations in patients with acute Acanthamoeba keratitis (AK) and fungal keratitis (FK), using laser in vivo confocal microscopy (IVCM). Methods A retrospective analysis of IVCM (Heidelberg Retina Tomograph 3/Rostock Cornea Module) images of 10 AK corneas and 4 FK corneas was performed, and the results compared with those of 10 normal and 12 acute herpetic keratitis (HK) corneas. Sub-basal corneal nerves were analyzed with respect to total number of nerves, main nerve trunks, branching pattern and total length of nerves per image, as well as tortuosity. For each variable, results for three frames were averaged and analyzed using analysis of variance. Results Total corneal nerve length was significantly (P < 0.0001) reduced in patients with AK (193.4 +/- 124.5 mu m) and FK (268.6 +/- 257.4 mu m) when compared with normal controls (3811.84 +/- 911.4 mu m). Total nerve counts in patients with AK (3.9 +/- 1.2) and FK (3.6 +/- 3.2) were significantly (P < 0.0001) decreased in comparison with normal controls (24.7 +/- 5.5). The number of main nerve trunks and nerve branching was found to be significantly lower in AK and FK corneas, when compared with controls. There was a statistically significant decrease in the above parameters when compared with HK controls. Conclusions The sub-basal corneal nerve plexus is significantly diminished in eyes with AK and FK, as demonstrated by IVCM. These results are more profound than previously reported findings of a diminished nerve plexus in HK. Eye (2012) 26, 126-132; doi:10.1038/eye.2011.270; published online 11 November 2011 C1 [Hamrah, P.] Harvard Univ, Ocular Surface Imaging Ctr, Massachusetts Eye & Ear Infirm, Sch Med,Dept Ophthalmol, Boston, MA 02114 USA. [Hamrah, P.] Harvard Univ, Cornea Serv, Massachusetts Eye & Ear Infirm, Sch Med,Dept Ophthalmol, Boston, MA 02114 USA. RP Hamrah, P (reprint author), Harvard Univ, Ocular Surface Imaging Ctr, Massachusetts Eye & Ear Infirm, Sch Med,Dept Ophthalmol, 243 Charles St, Boston, MA 02114 USA. EM pedram_hamrah@meei.harvard.edu FU NIH [K12-EY016335, K08-EY-020575]; New England Corneal Transplant Research Fund; Falk Medical Research Foundation FX This work was supported by NIH K12-EY016335, NIH K08-EY-020575, the New England Corneal Transplant Research Fund and Falk Medical Research Foundation. The funding organizations had no role in the design or conduct of this research. NR 15 TC 18 Z9 19 U1 1 U2 3 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-222X J9 EYE JI Eye PD JAN PY 2012 VL 26 IS 1 BP 126 EP 132 DI 10.1038/eye.2011.270 PG 7 WC Ophthalmology SC Ophthalmology GA 892UN UT WOS:000300311200015 PM 22079969 ER PT J AU Bamberg, F Truong, QA Koenig, W Schlett, CL Nasir, K Butler, J Kurtz, E Nikolaou, K Hoffmann, U Januzzi, JL AF Bamberg, Fabian Truong, Quynh A. Koenig, Wolfgang Schlett, Christopher L. Nasir, Khurram Butler, Javed Kurtz, Emily Nikolaou, Konstantin Hoffmann, Udo Januzzi, James L., Jr. TI Differential associations between blood biomarkers of inflammation, oxidation, and lipid metabolism with varying forms of coronary atherosclerotic plaque as quantified by coronary CT angiography SO INTERNATIONAL JOURNAL OF CARDIOVASCULAR IMAGING LA English DT Article DE Biomarkers; Atherosclerosis; Cardiac CT; Imaging; Coronary artery disease ID MULTIDETECTOR COMPUTED-TOMOGRAPHY; PERIPHERAL ARTERIAL-DISEASE; AMERICAN-HEART-ASSOCIATION; ACUTE CHEST-PAIN; REACTIVE-PROTEIN; SUBCLINICAL ATHEROSCLEROSIS; DENSITY-LIPOPROTEIN; ADIPOSE-TISSUE; OXIDIZED LDL; D-DIMER AB Although epidemiologic data link biomarkers of cardiovascular risk with incident and prevalent coronary artery disease, exact anatomic relationships between biomarkers and coronary atherosclerosis as measured by coronary CT angiography remain unclear. Patients with acute chest pain who ultimately had no evidence of acute coronary syndrome underwent contrast-enhanced 64-slice coronary CT angiography to determine presence, extent and composition of coronary atherosclerotic plaque. We determined the differences in levels of blood biomarkers measured at the time of the CT scan between different CT-based atherosclerotic plaque groups. Among 313 patients (mean age: 51.6 +/- A 11 years, 62% male) high-sensitivity C-reactive protein (hs-CRP) and matrix metalloproteinase-2 were associated with the extent of calcified plaque (P = 0.03 and P < 0.001), while hs-CRP and apolipoprotein A1 were associated with the extent of non-calcified plaque (P = 0.03 and P = 0.004; respectively). Despite a generally lower risk profile, subjects with exclusively non-calcified plaque had significantly higher levels of hs-CRP and oxidized low-density lipoprotein (P = 0.01 and P = 0.03; respectively) and lower levels of adiponectin (P = 0.03) when compared to subjects with calcified plaque (n = 130, 42%). Biomarkers reflecting inflammation, vascular remodeling, oxidation, and lipoprotein metabolism maybe associated with different patterns of coronary atherosclerosis as quantified by coronary CT angiography. C1 [Bamberg, Fabian; Nikolaou, Konstantin] Univ Munich, Klinikum Grosshadern, Dept Clin Radiol, D-81377 Munich, Germany. [Bamberg, Fabian; Truong, Quynh A.; Schlett, Christopher L.; Nasir, Khurram; Butler, Javed; Kurtz, Emily; Hoffmann, Udo] Harvard Univ, Massachusetts Gen Hosp, Cardiac MR PET CT Program, Sch Med, Boston, MA USA. [Januzzi, James L., Jr.] Harvard Univ, Div Cardiol, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Koenig, Wolfgang] Univ Ulm, Dept Internal Med Cardiol, Med Ctr, Ulm, Germany. RP Bamberg, F (reprint author), Univ Munich, Klinikum Grosshadern, Dept Clin Radiol, Marchioninistr 15, D-81377 Munich, Germany. EM fbamberg@med.lmu.de OI Nikolaou, Konstantin/0000-0003-2668-7325 FU NIH [R01 HL080053]; Siemens Medical Solutions; General Electrics Healthcare; Balson Scholar Fund; German National Merit Foundation; ERP Scholarship FX The authors would like to thank Gerlinde Trischler for excellent technical assistance of the blood biomarker measurements. This work was supported by the NIH (R01 HL080053), and in part supported by Siemens Medical Solutions and General Electrics Healthcare. Dr. Januzzi is supported in part by the Balson Scholar Fund. Dr. Schlett is supported in part by the German National Merit Foundation and the ERP Scholarship. NR 39 TC 11 Z9 11 U1 0 U2 4 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 1569-5794 J9 INT J CARDIOVAS IMAG JI Int. J. Cardiovasc. Imaging PD JAN PY 2012 VL 28 IS 1 BP 183 EP 192 DI 10.1007/s10554-010-9773-2 PG 10 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA 892TZ UT WOS:000300309800019 PM 21222039 ER PT J AU Lewiecki, EM Bilezikian, JP Jankowski, LG McCloskey, EV Miller, PD Morgan, SL Orwoll, ES Potts, JT AF Lewiecki, E. Michael Bilezikian, John P. Jankowski, Lawrence G. McCloskey, Eugene V. Miller, Paul D. Morgan, Sarah L. Orwoll, Eric S. Potts, John T., Jr. TI Proceedings of the 2011 Santa Fe Bone Symposium SO JOURNAL OF CLINICAL DENSITOMETRY LA English DT Article; Proceedings Paper CT Santa Fe Bone Symposium CY 2011 CL Santa Fe, NM SP Osteoporosis Fdn DE Denosumab; emerging; FRAX; new; osteoporosis; safety; treatment ID X-RAY ABSORPTIOMETRY; DUAL-PHOTON-ABSORPTIOMETRY; CALCIUM/VITAMIN-D SUPPLEMENTATION; CORONARY-ARTERY CALCIFICATION; PARATHYROID-HORMONE RECEPTOR; DENSITY PRECISION ASSESSMENT; FRACTURE INTERVENTION TRIAL; VITAMIN-D SUPPLEMENTATION; CHRONIC KIDNEY-DISEASE; CATHEPSIN-K INHIBITOR AB The 11th Santa Fe Bone Symposium was held in Santa Fe, NM, USA, on August 6-7, 2010. This annual event addresses the clinical relevance of recent scientific advances in the fields of osteoporosis and metabolic bone disease. The symposium format included plenary presentations, oral abstracts, and interactive panel discussions, with participation of clinicians, researchers, and bone densitometry technologists. Among the many topics included in the symposium were new developments in nutritional therapy for osteoporosis, parathyroid hormone for the assessment and treatment of skeletal disease, osteoporosis in men, new and emerging concepts in osteoporosis therapy, report on the 2010 International Society for Clinical Densitometry (ISCD)-International Osteoporosis Foundation FRAX Initiative and the ISCD Position Development Conference, balancing benefits and risks of bisphosphonate therapy, and an advanced bone densitometry workshop for clinicians and technologists. C1 [Lewiecki, E. Michael] New Mexico Clin Res & Osteoporosis Ctr, Albuquerque, NM 87106 USA. [Bilezikian, John P.] Columbia Univ, Coll Phys & Surg, New York, NY USA. [Jankowski, Lawrence G.] Illinois Bone & Joint Inst, Morton Grove, IL USA. [McCloskey, Eugene V.] Univ Sheffield, Sheffield, S Yorkshire, England. [Miller, Paul D.] Colorado Ctr Bone Res, Lakewood, CO USA. [Morgan, Sarah L.] Univ Alabama, Birmingham, AL USA. [Orwoll, Eric S.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Potts, John T., Jr.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. RP Lewiecki, EM (reprint author), New Mexico Clin Res & Osteoporosis Ctr, 300 Oak St NE, Albuquerque, NM 87106 USA. EM Lewiecki@aol.com OI Orwoll, Eric/0000-0002-8520-7355 NR 173 TC 5 Z9 5 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1094-6950 J9 J CLIN DENSITOM JI J. Clin. Densitom. PD JAN-MAR PY 2012 VL 15 IS 1 BP 1 EP 20 DI 10.1016/j.jocd.2011.11.004 PG 20 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 890JC UT WOS:000300139900001 PM 22284629 ER PT J AU Ishii, S Cauley, JA Crandall, CJ Srikanthan, P Greendale, GA Huang, MH Danielson, ME Karlamangla, AS AF Ishii, Shinya Cauley, Jane A. Crandall, Carolyn J. Srikanthan, Preethi Greendale, Gail A. Huang, Mei-Hua Danielson, Michelle E. Karlamangla, Arun S. TI Diabetes and Femoral Neck Strength: Findings from The Hip Strength Across the Menopausal Transition Study SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID BONE-MINERAL DENSITY; FRACTURE RISK; OSTEOPOROTIC FRACTURES; BODY-COMPOSITION; OLDER WOMEN; MELLITUS; ASSOCIATION; HEALTH; MEN; MASS AB Context: Diabetes mellitus is associated with increased hip fracture risk, despite being associated with higher bone mineral density in the femoral neck. Objective: The objective of the study was to test the hypothesis that composite indices of femoral neck strength, which integrate dual-energy x-ray absorptiometry derived femoral neck size, femoral neck areal bone mineral density, and body size and are inversely associated with hip fracture risk, would be lower in diabetics than in nondiabetics and be inversely related to insulin resistance, the primary pathology in type 2 diabetes. Design: This was a cross-sectional analysis. Setting and Participants: The study consisted of a multisite, multiethnic, community-dwelling sample of 1887 women in pre- or early perimenopause. Outcome Measurements: Composite indices for femoral neck strength in different failure modes (axial compression, bending, and impact) were measured. Results: Adjusted for age, race/ethnicity, menopausal stage, body mass index, smoking, physical activity, calcium and vitamin D supplementation, and study site, diabetic women had higher femoral neck areal bone mineral density [+0.25 SD, 95% confidence interval (CI) (+0.06, +0.44) SD] but lower composite strength indices [-0.20 SD, 95% CI (-0.38, -0.03) SD for compression, -0.19 SD, 95% CI (-0.38, -0.003) SD for bending, -0.19 SD, 95% CI (-0.37, -0.02) SD for impact] than non-diabetic women. There were graded inverse relationships between homeostasis model-assessed insulin resistance and all three strength indices, adjusted for the same covariates. Conclusions: Despite having higher bone density, diabetic women have lower indices of femoral neck strength relative to load, consistent with their documented higher fracture risk. Insulin resistance appears to play an important role in bone strength reduction in diabetes. (J Clin Endocrinol Metab 97: 190-197, 2012) C1 [Ishii, Shinya] Vet Affairs Greater Los Angeles Healthcare Syst, Geriatr Res Educ & Clin Ctr, Los Angeles, CA 90073 USA. [Cauley, Jane A.; Danielson, Michelle E.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA 15260 USA. [Greendale, Gail A.; Huang, Mei-Hua; Karlamangla, Arun S.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Div Geriatr, Los Angeles, CA 90095 USA. [Crandall, Carolyn J.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Div Gen Internal Med & Hlth Serv Res, Los Angeles, CA 90095 USA. [Srikanthan, Preethi] Univ Calif Los Angeles, David Geffen Sch Med, Res Ctr Alhambra, Dept Med,Div Clin Epidemiol & Preventat Med, Alhambra, CA 91801 USA. RP Ishii, S (reprint author), Univ Tokyo, Grad Sch Med, Dept Geriatr Med, Bunkyo Ku, 7-3-1 Hongo, Tokyo 1138655, Japan. EM sishii@ucla.edu OI Cauley, Jane A/0000-0003-0752-4408 FU National Institutes of Health (NIH), Department of Health and Human Services, through the National Institute on Aging (NIA); National Institute of Nursing Research; NIH Office of Research on Women's Health [NR004061, AG012505, AG012535, AG012531, AG012539, AG012546, AG012553, AG012554, AG012495]; NIA [AG026463, AG028748, AG033067]; Veterans Affairs Greater Los Angeles Healthcare System Geriatric Research, Education, and Clinical Center; Veterans Affairs FX SWAN was supported by the National Institutes of Health (NIH), Department of Health and Human Services, through the National Institute on Aging (NIA), the National Institute of Nursing Research, and the NIH Office of Research on Women's Health (Grants NR004061, AG012505, AG012535, AG012531, AG012539, AG012546, AG012553, AG012554, and AG012495). The Hip Strength Through the Menopausal Transition was supported by NIA Grant AG026463. The SWAN Hip Strength Substudy was supported by NIA Grant AG028748. The current study was also supported by NIA Grant AG033067. S.I. was supported by the Veterans Affairs Greater Los Angeles Healthcare System Geriatric Research, Education, and Clinical Center; and the Veterans Affairs Advanced Geriatrics Fellowship. NR 40 TC 31 Z9 33 U1 1 U2 8 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD JAN PY 2012 VL 97 IS 1 BP 190 EP 197 DI 10.1210/jc.2011-1883 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 893YM UT WOS:000300393800051 PM 22072739 ER PT J AU Lewkowitz-Shpuntoff, HM Hughes, VA Plummer, L Au, MG Doty, RL Seminara, SB Chan, YM Pitteloud, N Crowley, WF Balasubramanian, R AF Lewkowitz-Shpuntoff, Hilana M. Hughes, Virginia A. Plummer, Lacey Au, Margaret G. Doty, Richard L. Seminara, Stephanie B. Chan, Yee-Ming Pitteloud, Nelly Crowley, William F., Jr. Balasubramanian, Ravikumar TI Olfactory Phenotypic Spectrum in Idiopathic Hypogonadotropic Hypogonadism: Pathophysiological and Genetic Implications SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID GONADOTROPIN-RELEASING-HORMONE; LINKED KALLMANN-SYNDROME; OF-FUNCTION MUTATIONS; PROKINETICIN 2; RECEPTOR; DEFICIENCY; REPRODUCTION; MOLECULES; ADHESION; DELETION AB Context: The olfactory phenotype in patients with idiopathic hypogonadotropic hypogonadism (IHH) ranges from complete anosmia (Kallmann syndrome) to normosmia (normosmic IHH). However, the true prevalence of intermediary olfactory phenotypes (hyposmia) in IHH patients has not yet been assessed, and systematic correlations with anatomical and genetic abnormalities have not been reported. Objective: The objective of this study was to evaluate olfactory function in a large IHH cohort and correlate these findings with olfactory magnetic resonance imaging (MRI) and underlying genetic etiology. Design and Setting: We conducted a cross-sectional case-control study at an academic referral center. Patients: A total of 286 IHH patients (201 males and 85 females) and 2183 healthy historic controls (1011 males and 1172 females) were studied. Main Outcome Measures: We measured olfactory function using the University of Pennsylvania Smell Identification Test; in 208 subjects, the genetic etiology of IHH was ascertained by DNA sequencing; in a minor subset [39 of 286 subjects (13%)], olfactory structures were determined by MRI. Results: In the IHH cohort, 31.5% were anosmic, 33.6% were hyposmic, and 34.9% were normosmic. Most hyposmic (seven of 11) subjects with MRI data exhibited olfactory structure abnormalities. Of hyposmic subjects, 39.5% harbored mutations in genes involved in either GnRH neuronal migration or GnRH secretion. Conclusions: IHH subjects display a broad spectrum of olfactory function, with a significant hyposmic phenotype in nearly one third of subjects. The hyposmic subjects harbor mutations in genes affecting GnRH neuronal migration and its secretion, suggesting a pathophysiological overlap between Kallmann syndrome and normosmic IHH. Accurate olfactory phenotyping in IHH subjects will inform the pathophysiology of this condition and guide genetic testing. (J Clin Endocrinol Metab 97: E136-E144, 2012) C1 [Lewkowitz-Shpuntoff, Hilana M.; Hughes, Virginia A.; Plummer, Lacey; Au, Margaret G.; Seminara, Stephanie B.; Chan, Yee-Ming; Crowley, William F., Jr.; Balasubramanian, Ravikumar] Massachusetts Gen Hosp, Harvard Reprod Endocrine Sci Ctr, Reprod Endocrine Unit, Dept Med, Boston, MA 02114 USA. [Doty, Richard L.] Univ Penn, Sch Med, Ctr Smell & Taste, Philadelphia, PA 19104 USA. [Pitteloud, Nelly] CHU Vaudois, Endocrine Diabet & Metab Serv, CH-1011 Lausanne, Switzerland. [Chan, Yee-Ming] Childrens Hosp, Dept Med, Div Endocrinol, Boston, MA 02115 USA. RP Balasubramanian, R (reprint author), Massachusetts Gen Hosp, Harvard Reprod Endocrine Sci Ctr, Reprod Endocrine Unit, Dept Med, Bartlett Hall Extens,5th Floor,55 Fruit St, Boston, MA 02114 USA. EM rbalasubramanian@partners.org RI Doty, Richard/B-7623-2012; Doty, Richard/G-1602-2013; PITTELOUD, Nelly/K-2709-2014 FU Eunice Kennedy Shriver National Institute of Child Health and Human Development/National Institutes of Health as part of the Specialized Cooperative Centers [U54 HD028138-21]; U.S. Army [W81XWH-09-1-0467] FX This work was supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development/National Institutes of Health, through cooperative agreement U54 HD028138-21 as part of the Specialized Cooperative Centers Program in Reproduction and Infertility Research. R. L. D. is supported, in part, by U.S. Army Medical Research Acquisition Activity Grant W81XWH-09-1-0467. NR 40 TC 20 Z9 20 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 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD JAN PY 2012 VL 97 IS 1 BP E136 EP E144 DI 10.1210/jc.2011-2041 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 893YM UT WOS:000300393800022 PM 22072740 ER PT J AU Shaw, ND Klingman, KM Srouji, SS Histed, SN Hall, JE AF Shaw, N. D. Klingman, K. M. Srouji, S. S. Histed, S. N. Hall, J. E. TI Gonadotropin Responses to Estrogen-Positive and -Negative Feedback Are Identical in African-American and Caucasian Women SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID FOLLICLE-STIMULATING-HORMONE; ESTRADIOL; STEROIDS; INHIBIN; SURGES AB Context: Gonadotropin levels are similar in African-American women (AAW) and Caucasian women (CW), despite higher preovulatory estradiol (E2) levels in AAW, suggesting that AAW may be less sensitive to E2 feedback than CW. Objective: The aim of the study was to determine whether responsivity to estrogen feedback differs in AAW and CW. Design and Setting: Subjects were studied in the early follicular phase using a 5-d, graded E2 and progesterone infusion. Subjects: Healthy, normal-cycling AAW(n = 10) and CW (n = 13) aged 23-30 yr participated in the study. Main Outcome Measures: Blood samples were collected every 4 h and assayed for LH, FSH, E2, and progesterone. Results: There was no difference in E2-negative feedback on LH(nadir, 3.8 +/- 0.4 vs. 5.4 +/- 0.9 IU/liter; time of nadir, 33.2 +/- 3.3 vs. 32.3 +/- 2.7 h) or FSH (nadir, 3.1 +/- 0.4 vs. 3.1 +/- 0.3 IU/liter; time of nadir, 48.8 +/- 2.7 vs. 50.5 +/- 3.1 h) in AAW compared to CW. The two groups also demonstrated similar positive feedback responses of E2 on LH (peak, 80.3 +/- 13.3 vs. 73.1 +/- 11.6 IU/liter; time of peak, 80.4 +/- 4.3 vs. 86.5 +/- 3.1 h) and FSH (peak, 13.4 +/- 1.4 vs. 10.2 +/- 1.0 IU/liter; time of peak, 82.2 +/- 4.0 vs. 97.2 +/- 4.9 h). Conclusions: LH and FSH feedback responses to a controlled steroid infusion do not differ between AAW and CW, indicating that AAW do not have diminished hypothalamic-pituitary responsivity to E2. These studies support the concept of a threshold effect of E2 in generating LH-positive feedback, suggest pituitary insensitivity to differences in E2 of the magnitude observed in prior studies, and account for similarities in gonadotropins despite E2 differences in AAW compared with CW. (J Clin Endocrinol Metab 97: E106-E109, 2012) C1 [Shaw, N. D.; Klingman, K. M.; Srouji, S. S.; Histed, S. N.; Hall, J. E.] Massachusetts Gen Hosp, Reprod Endocrine Unit, Dept Med, Boston, MA 02114 USA. [Shaw, N. D.] Childrens Hosp, Div Endocrinol, Boston, MA 02115 USA. RP Hall, JE (reprint author), Massachusetts Gen Hosp, Reprod Endocrine Unit, Dept Med, BHX 5,55 Fruit St, Boston, MA 02114 USA. EM jehall@partners.org OI Shaw, Natalie/0000-0002-0847-9170 FU National Institutes of Health (NIH) [R01HD 42708, M01 RR01066, 5T32 HD007396]; Harvard Clinical and Translational Science Center [UL1 RR 025758] FX This work was supported by National Institutes of Health (NIH) Grants R01HD 42708 and M01 RR01066. N.D.S. received fellowship support from the NIH (5T32 HD007396) and from the Scholars in Clinical Science program of Harvard Catalyst [The Harvard Clinical and Translational Science Center (award no. UL1 RR 025758) and financial contributions from Harvard University and its affiliated academic health care centers). The content is solely the responsibility of the authors and does not necessarily represent the official views of Harvard Catalyst, Harvard University and its affiliated academic health care centers, the National Center for Research Resources, or the NIH. NR 14 TC 1 Z9 1 U1 0 U2 2 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 JAN PY 2012 VL 97 IS 1 BP E106 EP E109 DI 10.1210/jc.2011-2102 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 893YM UT WOS:000300393800017 PM 22049179 ER PT J AU Gordon, CR Susarla, SM Peacock, ZS Kaban, LB Yaremchuk, MJ AF Gordon, Chad R. Susarla, Srinivas M. Peacock, Zachary S. Kaban, Leonard B. Yaremchuk, Michael J. TI Le Fort-Based Maxillofacial Transplantation: Current State of the Art and a Refined Technique Using Orthognathic Applications SO JOURNAL OF CRANIOFACIAL SURGERY LA English DT Article DE Craniomaxillofacial surgery; Le Fort osteotomy; maxillofacial allotransplant; face transplant; osteocutaneous; facial composite tissue allograft; orthognathic ID FACIAL ALLOGRAFT TRANSPLANTATION; TOTAL HUMAN FACE; CADAVER; ALLOTRANSPLANTATION; OUTCOMES; HUMANS; RECOMMENDATIONS; APPEARANCE; MODEL AB Following encouraging results from the first 6 maxillofacial allotransplants, there has been a dramatic rise in interest worldwide. Numerous groups are now devoting resources to increase the frequency of these complex procedures, and with this, the craniomaxillofacial surgeon should become familiar with the emerging state of the art. This article reviews the evolution of Le Fort-based cadaveric studies pertaining to maxillofacial allotransplantation, briefly describes the clinical reports through 2010, and introduces a refined technique applying orthognathic applications. Preliminary studies over the last 5 years have highlighted the challenges associated with transplanting skeletal components, and clinical results presented thus far have been extremely promising. However, a notable area for improvement is suboptimal facial-skeletal harmony and profile in the context of sagittal skeletal projection and maxillomandibular relation. To our knowledge, orthognathic planning as applied to osteocutaneous face transplantation has not been described. Many recipients seen thus far demonstrate some degree of malocclusion and suboptimal harmony, as expected, given the donor-to-recipient skeletal/jaw discrepancies. Given that the goal is to improve function as well as form, the importance of orthognathic planning cannot be overstated with respect to optimizing harmony, profile, and occlusion. Preoperative planning, including generation of donor/recipient dental cast models, as described herein for the first time, is essential. C1 [Gordon, Chad R.; Yaremchuk, Michael J.] Harvard Univ, Sch Med, Dept Surg, Massachusetts Gen Hosp,Div Plast & Reconstruct Su, Boston, MA 02115 USA. [Susarla, Srinivas M.; Peacock, Zachary S.; Kaban, Leonard B.] Harvard Univ, Sch Dent Med, Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Boston, MA 02115 USA. [Gordon, Chad R.] Johns Hopkins Univ, Sch Med, Dept Plast & Reconstruct Surg, Baltimore, MD USA. RP Gordon, CR (reprint author), Johns Hopkins Univ Hosp, Dept Plast & Reconstruct Surg, JHOC 8th Floor,Suite 8161, Baltimore, MD 21287 USA. EM cgordon@jhmi.edu OI Susarla, Srinivas/0000-0003-0155-8260 FU New England Society of Plastic and Reconstructive Surgeons FX Dr Gordon received the 2011 Joseph E. Murray, MD Award from the New England Society of Plastic and Reconstructive Surgeons for his paper on osteocutaneous maxillofacial allotransplantation. NR 32 TC 16 Z9 16 U1 1 U2 9 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1049-2275 J9 J CRANIOFAC SURG JI J. Craniofac. Surg. PD JAN PY 2012 VL 23 IS 1 BP 81 EP 87 DI 10.1097/SCS.0b013e318240ca77 PG 7 WC Surgery SC Surgery GA 891RS UT WOS:000300234900045 PM 22337380 ER PT J AU Abbott, MM Rogers, GF Proctor, MR Busa, K Meara, JG AF Abbott, Megan M. Rogers, Gary F. Proctor, Mark R. Busa, Kathleen Meara, John G. TI Cost of Treating Sagittal Synostosis in the First Year of Life SO JOURNAL OF CRANIOFACIAL SURGERY LA English DT Article DE Craniosynostosis; sagittal; endoscopic; cost analysis; cranial vault remodeling ID ENDOSCOPIC CRANIECTOMY; MOLDING THERAPY; CRANIOSYNOSTOSIS; MANAGEMENT AB Background: Endoscopically assisted suturectomy (EAS) has been reported to reduce the morbidity and cost of treating sagittal synostosis when compared with traditional open cranial vault remodeling (CVR) procedures. Whereas the former claim is well substantiated and intuitive, the latter has not been validated by rigorous cost analysis. Methods: Patient medical records and financial database reports were culled retrospectively to determine the total cost associated with both EAS and CVR during 1 year of care. Recorded cost data included physician and hospital services, orthotic equipment and fittings, and indirect patient cost. Results: Ten patients treated with CVR were compared with 10 patients who underwent EAS. The CVR patients incurred greater costs in nearly all categories studied, including overall 1-year costs, physician services, hospital services, supplies/equipment, medications/intravenous fluids, and laboratory and blood bank services. Postoperative costs were greater in the EAS group, primarily because of the cost associated with orthotic services and indirect patient costs for travel and lost work. However, overall indirect patient costs for the whole year did not differ between the groups. One-year median costs were $55,121 for CVR and $23,377 for EAS. Early clinical results were similar for the 2 groups. Conclusions: Cranial vault remodeling was more costly in the first year of treatment than EAS, although indirect patient costs were similar. The favorable cost of EAS compared with CVR provides further justification to consider this procedure as first-line treatment of sagittal synostosis in young infants. C1 [Abbott, Megan M.; Rogers, Gary F.; Busa, Kathleen; Meara, John G.] Childrens Hosp Boston, Dept Plast & Oral Surg, Boston, MA 02115 USA. [Abbott, Megan M.; Rogers, Gary F.; Proctor, Mark R.; Meara, John G.] Harvard Univ, Sch Med, Boston, MA USA. [Abbott, Megan M.] Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. [Proctor, Mark R.] Childrens Hosp Boston, Dept Neurosurg, Boston, MA 02115 USA. RP Meara, JG (reprint author), Childrens Hosp Boston, Dept Plast & Oral Surg, 300 Longwood Ave,Enders 1, Boston, MA 02115 USA. EM john.meara@childrens.harvard.edu NR 13 TC 11 Z9 11 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1049-2275 J9 J CRANIOFAC SURG JI J. Craniofac. Surg. PD JAN PY 2012 VL 23 IS 1 BP 88 EP 93 DI 10.1097/SCS.0b013e318240f965 PG 6 WC Surgery SC Surgery GA 891RS UT WOS:000300234900046 PM 22337381 ER PT J AU Abbott, MM Meara, JG AF Abbott, Megan M. Meara, John G. TI Patient Protection and Affordable Care Act: Implications for Pediatric Plastic Surgery SO JOURNAL OF CRANIOFACIAL SURGERY LA English DT Article DE Patient protection and affordable care act; health care reform; pediatric plastic surgery; health care policy AB Passage of the Patient Protection and Affordable Care Act (PPACA) has stimulated wide debate in the medical and surgical community. Endorsed by the American Medical Association and a number of primary care-focused organizations, the American College of Surgeons (ACS) and nearly all other surgical associations opposed the bill. This divergence stems not from direct disagreement over provisions in the bill but from opposition to or support of certain provisions with direct implications for the physicians represented by a given organization, as well as the relative importance of provisions for which these organizations share a common opinion. Regarding the field of pediatric plastic surgery, the surgical perspective of the ACS and the American Society of Plastic Surgeons and the medical perspective of the American Academy of Pediatrics align on many issues. Given the lack of specificity of any of the provisions for a field as specialized as pediatric plastic surgery, this review will focus on broader implications of the PPACA both for medical and surgical needs of pediatric patients and for the surgeons providing their care. The provisions of the PPACA are distributed along an implementation timeline, with some major changes having already occurred. The popularity of some of the early provisions, many pertaining to the pediatric population, has implications for any attempt at repeal of the law as a whole in coming years. Despite its daunting length, the PPACA can be approached by considering its provisions in 4 major categories: increased consumer protections, increased accountability for insurers, increased access to affordable care, and quality and cost improvement. C1 [Abbott, Megan M.; Meara, John G.] Childrens Hosp, Dept Plast & Oral Surg, Boston, MA 02115 USA. [Abbott, Megan M.; Meara, John G.] Harvard Univ, Sch Med, Boston, MA USA. [Abbott, Megan M.] Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. RP Meara, JG (reprint author), Childrens Hosp, Dept Plast & Oral Surg, 300 Longwood Ave,Enders 1, Boston, MA 02115 USA. EM john.meara@childrens.harvard.edu NR 9 TC 2 Z9 2 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1049-2275 J9 J CRANIOFAC SURG JI J. Craniofac. Surg. PD JAN PY 2012 VL 23 IS 1 BP 217 EP 219 DI 10.1097/SCS.0b013e318241b8a4 PG 3 WC Surgery SC Surgery GA 891RS UT WOS:000300234900077 PM 22337412 ER PT J AU Leonard, DA Gordon, CR Sachs, DH Cetrulo, CL AF Leonard, David A. Gordon, Chad R. Sachs, David H. Cetrulo, Curtis L., Jr. TI Immunobiology of Face Transplantation SO JOURNAL OF CRANIOFACIAL SURGERY LA English DT Article DE Face transplant; composite tissue allotransplant; immune biology; facial allograft ID KIDNEY ALLOGRAFTS; MIXED CHIMERISM; MINIATURE SWINE; BONE-MARROW; TOLERANCE; CELLS; MODEL; INDUCTION; GRAFT; ALLOTRANSPLANTATION AB Fourteen face transplants have been performed worldwide since the procedure was successfully introduced in 2005. Vascularized composite tissue allotransplantation may now be considered a viable option for the repair of complex craniofacial defects, for which the results of autologus reconstruction remain suboptimal. However, the benefits must be balanced against the risks inherent in major surgery and the adverse effects of lifelong immunosuppression. In this article, we review the current practice and areas of controversy in facial vascularized composite tissue allotransplantation with particular respect to the unique immunobiology of this procedure. We also describe promising recent advances in immunotherapy and tolerance induction strategies that may soon reach clinical application. C1 [Leonard, David A.; Sachs, David H.; Cetrulo, Curtis L., Jr.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr, Boston, MA USA. [Gordon, Chad R.; Cetrulo, Curtis L., Jr.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Plast Surg, Boston, MA USA. RP Cetrulo, CL (reprint author), Massachusetts Gen Hosp E, Transplantat Biol Res Ctr, Room 9019,Bldg 149,13th St, Boston, MA 02129 USA. EM curt.cetrulo@tbrc.mgh.harvard.edu FU Musculoskeletal Transplant Foundation; Melina Nakos Foundation FX This work was supported by the Musculoskeletal Transplant Foundation and the Melina Nakos Foundation. NR 31 TC 9 Z9 9 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1049-2275 J9 J CRANIOFAC SURG JI J. Craniofac. Surg. PD JAN PY 2012 VL 23 IS 1 BP 268 EP 271 DI 10.1097/SCS.0b013e318241b8e0 PG 4 WC Surgery SC Surgery GA 891RS UT WOS:000300234900088 PM 22337423 ER PT J AU Bekris, LM Lutz, F Yu, CE AF Bekris, Lynn M. Lutz, Franziska Yu, Chang-En TI Functional analysis of APOE locus genetic variation implicates regional enhancers in the regulation of both TOMM40 and APOE SO JOURNAL OF HUMAN GENETICS LA English DT Article DE APOC1; APOE; BCR; enhancer; luciferase reporter assay; ME1; regulation; TOMM40 ID GENOME-WIDE ASSOCIATION; APOLIPOPROTEIN-E GENE; ONSET ALZHEIMERS-DISEASE; LINKAGE DISEQUILIBRIUM; SUSCEPTIBILITY GENES; QUANTITATIVE TRAIT; PROTEIN-LEVELS; EXPRESSION; BRAIN; RISK AB Genetic variation within the apolipoprotein E gene (APOE) locus is associated with late-onset Alzheimer's disease risk and quantitative traits as well as apoE expression in multiple tissues. The aim of this investigation was to explore the influence of APOE locus cis-regulatory element enhancer region genetic variation on regional gene promoter activity. Luciferase reporter constructs containing haplotypes of APOE locus gene promoters; APOE, APOC1 and TOMM40, and regional putative enhancers; TOMM40 intervening sequence (IVS) 2-4, TOMM40 IVS6 poly-T, as well as previously described enhancers; multienhancer 1 (ME1), or brain control region (BCR), were evaluated for their effects on luciferase activity in three human cell lines. Results of this investigation demonstrate that in SHSY5Y cells, the APOE promoter is significantly influenced by the TOMM40 IVS2-4 and ME1, and the TOMM40 promoter is significantly influenced by the TOMM40 IVS6 poly-T, ME1 and BCR. In HepG2 cells, the TOMM40 promoter is significantly influenced by all four enhancers, whereas the APOE promoter is not influenced by any of the enhancers. The main novel finding of this investigation was that multiple APOE locus cis-elements influence both APOE and TOMM40 promoter activity according to haplotype and cell type, suggesting that a complex transcriptional regulatory structure modulates regional gene expression. Journal of Human Genetics (2012) 57, 18-25; doi: 10.1038/jhg.2011.123; published online 17 November 2011 C1 [Bekris, Lynn M.] Univ Washington, Dept Med, Div Gerontol & Geriatr Med, VA Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. [Bekris, Lynn M.; Lutz, Franziska; Yu, Chang-En] VA Puget Sound Hlth Care Syst, Geriatr Res Educ & Clin Ctr, Seattle, WA USA. RP Bekris, LM (reprint author), Univ Washington, Dept Med, Div Gerontol & Geriatr Med, VA Puget Sound Hlth Care Syst, Box 358280 VAPSHCS GRECC S182,1660 S Columbian Wa, Seattle, WA 98108 USA. EM lbekris@u.washington.edu FU US Department of Veterans Affairs; Office of Research and Development Biomedical Laboratory; National Institutes of Health/National Institutes on Aging [1K99AG034214-01A1] FX This work was supported in part by the US Department of Veterans Affairs, Office of Research and Development Biomedical Laboratory Research Program and the National Institutes of Health/National Institutes on Aging Grant 1K99AG034214-01A1. We thank J Anthony Gill for the editing of the manuscript. NR 33 TC 36 Z9 36 U1 2 U2 7 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1434-5161 J9 J HUM GENET JI J. Hum. Genet. PD JAN PY 2012 VL 57 IS 1 BP 18 EP 25 DI 10.1038/jhg.2011.123 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA 892PI UT WOS:000300297700006 PM 22089642 ER PT J AU Sanchez-Reilly, S Ross, JS AF Sanchez-Reilly, Sandra Ross, Jeanette S. TI Hospice and Palliative Medicine: Curriculum Evaluation and Learner Assessment in Medical Education SO JOURNAL OF PALLIATIVE MEDICINE LA English DT Article ID OF-LIFE CARE; STUDENTS; COMPETENCES; PROJECT; RESIDENTS; OUTCOMES; SCHOOLS AB Major efforts have been pursued to improve palliative care education for physicians at all levels of their training. Such changes include the incorporation of palliative care curriculum and guidelines, an established process for competency-based evaluation and certification, faculty development, innovative educational experiences, the improvement of textbooks, and the establishment of accredited palliative medicine fellowships. Hospice and palliative medicine (HPM) has been clearly defined as a subspecialty and a crucial area of medical education. As innovative curricular approaches have become available to educate medical and other interprofessional trainees, this article aims to describe different models and methods applied in curriculum evaluation, tailoring such approaches to the field of palliative medicine. A stepwise process of curriculum development and evaluation is described, focusing on available curriculum evaluation competency-based tools for each level of learners. As HPM evolves and its educational programs grow, curriculum evaluation will provides invaluable feedback to institutions and programs in many ways. C1 [Sanchez-Reilly, Sandra] Univ Texas Hlth Sci Ctr San Antonio, Div Geriatr Gerontol & Palliat Med, San Antonio, TX 78229 USA. [Ross, Jeanette S.] Univ Texas Hlth Sci Ctr San Antonio, Dept Family & Community Med, San Antonio, TX 78229 USA. [Ross, Jeanette S.] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA. [Sanchez-Reilly, Sandra] S Texas Vet Hlth Care Syst, GEC, San Antonio, TX 78229 USA. [Sanchez-Reilly, Sandra] S Texas Vet Hlth Care Syst, GRECC, San Antonio, TX 78229 USA. RP Sanchez-Reilly, S (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Div Geriatr Gerontol & Palliat Med, 7703 Floyd Curl Dr,MC 7875, San Antonio, TX 78229 USA. EM sanchezreill@uthscsa.edu NR 58 TC 10 Z9 10 U1 0 U2 2 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1096-6218 J9 J PALLIAT MED JI J. Palliat. Med. PD JAN PY 2012 VL 15 IS 1 BP 116 EP 122 DI 10.1089/jpm.2011.0155 PG 7 WC Health Care Sciences & Services SC Health Care Sciences & Services GA 891HK UT WOS:000300207600021 PM 22268408 ER PT J AU Solomon, B Shaw, AT AF Solomon, Benjamin Shaw, Alice T. TI Are Anaplastic Lymphoma Kinase Gene Rearrangements in Non-small Cell Lung Cancer Prognostic, Predictive, or Both? SO JOURNAL OF THORACIC ONCOLOGY LA English DT Editorial Material ID EML4-ALK FUSION; BREAST C1 [Solomon, Benjamin] Peter MacCallum Canc Ctr, Dept Med Oncol, Melbourne, Vic 3002, Australia. [Shaw, Alice T.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. RP Solomon, B (reprint author), Peter MacCallum Canc Ctr, Dept Med Oncol, St Andrews Pl, Melbourne, Vic 3002, Australia. EM ben.solomon@petermac.org NR 20 TC 4 Z9 4 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1556-0864 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD JAN PY 2012 VL 7 IS 1 BP 5 EP 7 DI 10.1097/JTO.0b013e31823f1289 PG 3 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 892SJ UT WOS:000300305600003 PM 22173659 ER PT J AU Roelofs, E Engelsman, M Rasch, C Persoon, L Qamhiyeh, S de Ruysscher, D Verhaegen, F Pijls-Johannesma, M Lambin, P AF Roelofs, Erik Engelsman, Martijn Rasch, Coen Persoon, Lucas Qamhiyeh, Sima de Ruysscher, Dirk Verhaegen, Frank Pijls-Johannesma, Madelon Lambin, Philippe CA ROCOCO Consortium TI Results of a Multicentric In Silico Clinical Trial (ROCOCO) Comparing Radiotherapy with Photons and Protons for Non-small Cell Lung Cancer SO JOURNAL OF THORACIC ONCOLOGY LA English DT Article DE In silico planning study; Multicentric trial; Lung cancer; NSCLC; Radiotherapy; Particle therapy; Dose escalation ID MODULATED RADIATION-THERAPY; PARTICLE THERAPY; COST-EFFECTIVENESS; DOSE PRESCRIPTION; INDUCED DYSPHAGIA; HADRON THERAPY; BEAM THERAPY; STAGE-I; CHEMOTHERAPY; CONSTRAINTS AB Introduction: This multicentric in silico trial compares photon and proton radiotherapy for non-small cell lung cancer patients. The hypothesis is that proton radiotherapy decreases the dose and the volume of irradiated normal tissues even when escalating to the maximum tolerable dose of one or more of the organs at risk (OAR). Methods: Twenty-five patients, stage IA-IIIB, were prospectively included. On 4D F-18-labeled fluorodeoxyglucose-positron emission tomography-computed tomography scans, the gross tumor, clinical and planning target volumes, and OAR were delineated. Three-dimensional conformal radiotherapy (3DCRT) and intensity-modulated radiotherapy (IMRT) photon and passive scattered conformal proton therapy (PSPT) plans were created to give 70 Gy to the tumor in 35 fractions. Dose (de-)escalation was performed by rescaling to the maximum tolerable dose. Results: Protons resulted in the lowest dose to the OAR, while keeping the dose to the target at 70 Gy. The integral dose (ID) was higher for 3DCRT (59%) and IMRT (43%) than for PSPT. The mean lung dose reduced from 18.9 Gy for 3DCRT and 16.4 Gy for IMRT to 13.5 Gy for PSPT. For 10 patients, escalation to 87 Gy was possible for all 3 modalities. The mean lung dose and ID were 40 and 65% higher for photons than for protons, respectively. Conclusions: The treatment planning results of the Radiation Oncology Collaborative Comparison trial show a reduction of ID and the dose to the OAR when treating with protons instead of photons, even with dose escalation. This shows that PSPT is able to give a high tumor dose, while keeping the OAR dose lower than with the photon modalities. C1 [Roelofs, Erik; Persoon, Lucas; Qamhiyeh, Sima; de Ruysscher, Dirk; Verhaegen, Frank; Pijls-Johannesma, Madelon; Lambin, Philippe] Maastricht Univ Med Ctr, GROW Sch Oncol & Dev Biol, Dept Radiat Oncol MAASTRO, Maastricht, Netherlands. [Engelsman, Martijn] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Engelsman, Martijn] Harvard Univ, Sch Med, MGH, Boston, MA USA. [Rasch, Coen] Antoni van Leeuwenhoek Hosp, Netherlands Canc Inst, Dept Radiotherapy, Amsterdam, Netherlands. [Verhaegen, Frank] McGill Univ, Montreal, PQ, Canada. RP Roelofs, E (reprint author), Maastro Clin, POB 3035, NL-6202 NA Maastricht, Netherlands. EM Erik.Roelofs@maastro.nl OI schilstra, cornelis/0000-0002-1526-1743; Roelofs, Erik/0000-0003-2172-8669; Dekker, Andre/0000-0002-0422-7996 NR 64 TC 40 Z9 41 U1 1 U2 16 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1556-0864 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD JAN PY 2012 VL 7 IS 1 BP 165 EP 176 DI 10.1097/JTO.0b013e31823529fc PG 12 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 892SJ UT WOS:000300305600025 PM 22071782 ER PT J AU Pietanza, MC Lynch, TJ Lara, PN Cho, J Yanagihara, RH Vrindavanam, N Chowhan, NM Gadgeel, SM Pennell, NA Funke, R Mitchell, B Wakelee, HA Miller, VA AF Pietanza, M. Catherine Lynch, Thomas James, Jr. Lara, Primo N., Jr. Cho, John Yanagihara, Ronald H. Vrindavanam, Nandagopal Chowhan, Naveed Mahfooz Gadgeel, Shirish M. Pennell, Nathan A. Funke, Roel Mitchell, Ben Wakelee, Heather A. Miller, Vincent A. TI XL647-A Multitargeted Tyrosine Kinase Inhibitor Results of a Phase II Study in Subjects with Non-small Cell Lung Cancer Who Have Progressed after Responding to Treatment with Either Gefitinib or Erlotinib SO JOURNAL OF THORACIC ONCOLOGY LA English DT Article DE EGFR-sensitizing mutation; EGFR-resistance mutation; Tyrosine kinase inhibitors; Acquired resistance; Molecular analysis ID GROWTH-FACTOR RECEPTOR; ACQUIRED-RESISTANCE; EGFR MUTATION; T790M MUTATIONS; GENE-MUTATIONS; GEFITINIB; ERLOTINIB; MUTANT; TUMORS; ADENOCARCINOMAS AB Introduction: Although patients with non-small cell lung cancer (NSCLC) whose tumors harbor epidermal growth factor receptor (EGFR) activating mutations commonly experience significant regressions when treated with erlotinib or gefitinib, they uniformly develop resistance to these agents. The secondary EGFR T790M mutation is found in 50% of patients with acquired resistance. Herein, we studied XL647, an oral small molecule inhibitor of multiple receptor tyrosine kinases, including EGFR, VEGFR2, HER2, and EphB4, in NSCLC patients known or suspected of having tumors harboring T790M. Methods: Eligible patients included those with relapsed or recurrent advanced NSCLC who progressed after >= 12 weeks of stable disease or response to erlotinib or gefitinib and/or those patients with a documented EGFR T790M. XL647 300 mg was administered once daily. The primary end point was objective response rate. Pretreatment plasma samples were collected for mutation testing of circulating tumor DNA. Results: Forty-one patients were enrolled; 33 were evaluable for efficacy. One partial response was observed (response rate 3% and 90% confidence interval, 0% to 14%). Of patients whose tumors harbored T790M, 67% (8/12) had progression of disease as best response compared with 14% (3/21) of those without this mutation. Plasma samples from 40 patients were available for mutation testing, 14 (35%) of which were found to have EGFR mutations. Conclusions: The 3% response rate observed did not meet the prespecified threshold to recommend further study of XL647 in patients who develop acquired resistance to erlotinib or gefitinib. Patients with T790M had a significantly worse progression-free survival. C1 [Pietanza, M. Catherine; Miller, Vincent A.] Cornell Univ, Mem Sloan Kettering Canc, Div Solid Tumor Oncol, Dept Med,Thorac Oncol Serv, New York, NY 10065 USA. [Pietanza, M. Catherine; Miller, Vincent A.] Cornell Univ, Weill Med Coll, New York, NY 10065 USA. [Lynch, Thomas James, Jr.; Pennell, Nathan A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Lynch, Thomas James, Jr.; Pennell, Nathan A.] Harvard Univ, Sch Med, Boston, MA USA. [Lara, Primo N., Jr.] Univ Calif Davis, Ctr Canc, Dept Med Hematol & Oncol, Sacramento, CA 95817 USA. [Cho, John] New Bern Canc Ctr, New Bern, NC USA. [Chowhan, Naveed Mahfooz] Floyd Mem Canc Ctr Indiana, New Albany, IN USA. [Gadgeel, Shirish M.] Wayne State Univ, Dept Med, Div Hematol Oncol, Karmanos Canc Inst, Detroit, MI 48202 USA. [Funke, Roel; Mitchell, Ben] Exelixis Inc, So San Francisco, CA USA. [Wakelee, Heather A.] Stanford Univ, Med Ctr, Dept Med, Thorac Oncol Serv, Stanford, CA 94305 USA. [Vrindavanam, Nandagopal] Signal Point Hematol Oncol, Middletown, OH USA. RP Pietanza, MC (reprint author), Cornell Univ, Mem Sloan Kettering Canc, Div Solid Tumor Oncol, Dept Med,Thorac Oncol Serv, 1275 York Ave, New York, NY 10065 USA. EM pietanzm@mskcc.org FU Exelixis, Inc.; Exelixis FX Supported by Exelixis, Inc.; Thomas J. Lynch has served as a consultant for Merck, Supergen, and BI; is on the Board of Directors for Infinity; and holds an EGFR mutation testing patent from Partners H. C. Primo N. Lara, Jr., has served as a consultant to and has received research funding from Exelixis. Ronald Yanagihara has received funding to register and treat patients on this protocol. Nandagopal Vrindavanam's organization has been paid to perform a clinical trial involving the investigational product, XL647. Roel Funke was employed by Exelixis until September 2010 and continues to hold stock in the organization. Ben Mitchel is employed by Exelixis. Heather A. Wakelee reports that Stanford University received resources to conduct this study and other trials from Exelixis, for which she served as the P. I. Vincent A. Miller has served as an advisor to Pfizer, Boehringer Ingenheim, Roche, OSI Pharmaceuticals, ArQule, and Genentech. NR 36 TC 30 Z9 31 U1 0 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1556-0864 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD JAN PY 2012 VL 7 IS 1 BP 219 EP 226 DI 10.1097/JTO.0b013e31822eebf9 PG 8 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 892SJ UT WOS:000300305600032 PM 22011666 ER PT S AU Vadysirisack, DD Ellisen, LW AF Vadysirisack, Douangsone D. Ellisen, Leif W. BE Weichhart, T TI mTOR Activity Under Hypoxia SO MTOR: METHODS AND PROTOCOLS SE Methods in Molecular Biology LA English DT Article; Book Chapter DE mTOR; Hypoxia; Phospho-4E-BP1; Phospho-p70S6K; Phospho-S6; REDD1; TSC2; 14-3-3; Protein translation ID MESSENGER-RNA TRANSLATION; ENERGY STRESS; MAMMALIAN TARGET; CELL-GROWTH; PHOSPHORYLATION; MECHANISMS; CANCER; RAPAMYCIN; PATHWAY; KINASE AB The adaptive response to hypoxia, low oxygen tension, involves inhibition of energy-intensive cellular processes including protein translation. This effect is mediated in part through a decrease in the kinase activity of mammalian target of rapamycin complex I (mTORC1), a master regulator of protein translation. The principle mechanism for hypoxia-induced mTORC1 inhibition, however, was not elucidated until recently. Our work has demonstrated that the stress-induced protein REDD1 is essential for hypoxia regulation of mTORC1 activity and has further defined the molecular mechanism whereby REDD1 represses mTORC1 activity under hypoxic stress. Using our studies with REDD1 as an example, we describe in detail biochemical approaches to assess mTORC1 activity in the hypoxic response. Here, we provide methodologies to monitor signaling components both downstream and upstream of the hypoxia-induced mTORC1 inhibitory pathway. These methodologies will serve as valuable tools for researchers seeking to understand mTORC1 dysregulation in the context of hypoxic stress. C1 [Vadysirisack, Douangsone D.; Ellisen, Leif W.] Harvard Univ, Massachusetts Gen Hosp, Ctr Canc, Sch Med, Boston, MA 02114 USA. RP Vadysirisack, DD (reprint author), Harvard Univ, Massachusetts Gen Hosp, Ctr Canc, Sch Med, Boston, MA 02114 USA. FU NCI NIH HHS [F32 CA150633, K08 CA082831, R01 CA122589] NR 19 TC 9 Z9 9 U1 0 U2 1 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-61779-429-2 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2012 VL 821 BP 45 EP 58 DI 10.1007/978-1-61779-430-8_4 D2 10.1007/978-1-61779-430-8 PG 14 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BYN18 UT WOS:000299398200004 PM 22125059 ER PT S AU Papageorgiou, A Avruch, J AF Papageorgiou, Angela Avruch, Joseph BE Weichhart, T TI A Genome-wide RNAi Screen for Polypeptides that Alter rpS6 Phosphorylation SO MTOR: METHODS AND PROTOCOLS SE Methods in Molecular Biology LA English DT Article; Book Chapter DE rpS6; Phosphorylation; mTOR; Genome wide; RNAi; Screen; Immunofluorescence; Pancreatic cancer ID P70 S6 KINASE; AMINO-ACID REGULATION; IN-VITRO; PROTEIN-KINASE; MTOR INHIBITORS; DRUG DISCOVERY; CANCER-THERAPY; PATHWAY; VIVO; IDENTIFICATION AB Mammalian target of rapamycin (mTOR) is a giant protein kinase that controls cell proliferation, growth, and metabolism. mTOR is regulated by nutrient availability, by mitogens, and by stress, and operates through two independently regulated hetero-oligomeric complexes. We have attempted to identify the cellular components necessary to maintain the activity of mTOR complex 1 (mTORC1), the amino acid-dependent, rapamycin-inhibitable complex, using a whole genome approach involving RNAi-induced depletion of cellular polypeptides. We have used a pancreatic ductal adenocarcinoma (PDAC) cell line, Mia-PaCa for this screen; as with many pancreatic cancers, these cells exhibit constitutive activation of mTORC1. PDAC is the most common form of pancreatic cancer and the 5-year survival rate remains 3-5% despite current nonspecific and targeted therapies. Although rapamycin-related mTOR inhibitors have yet to demonstrate encouraging clinical responses, it is now evident that this class of compounds is capable of only partial mTORC1 inhibition. Identifying previously unappreciated proteins needed for maintenance of mTORC1 activity may provide new targets and lead to the development of beneficial therapies for pancreatic cancer. C1 [Papageorgiou, Angela; Avruch, Joseph] Massachusetts Gen Hosp, Diabet Unit, Boston, MA 02114 USA. [Papageorgiou, Angela; Avruch, Joseph] Massachusetts Gen Hosp, Med Serv, Boston, MA 02114 USA. [Papageorgiou, Angela; Avruch, Joseph] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. [Papageorgiou, Angela; Avruch, Joseph] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. RP Papageorgiou, A (reprint author), Massachusetts Gen Hosp, Diabet Unit, Boston, MA 02114 USA. FU NCI NIH HHS [CA73818, R01 CA073818]; NIDDK NIH HHS [DK17776, P30 DK040561, P30 DK057521, R37 DK017776] NR 28 TC 2 Z9 2 U1 0 U2 1 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-61779-429-2 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2012 VL 821 BP 187 EP 214 DI 10.1007/978-1-61779-430-8_11 D2 10.1007/978-1-61779-430-8 PG 28 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BYN18 UT WOS:000299398200011 PM 22125066 ER PT S AU Liu, QS Kang, SA Thoreen, CC Hur, W Wang, JH Chang, JW Markhard, A Zhang, JM Sim, T Sabatini, DM Gray, NS AF Liu, Qingsong Kang, Seong A. Thoreen, Carson C. Hur, Wooyoung Wang, Jinhua Chang, Jae Won Markhard, Andrew Zhang, Jianming Sim, Taebo Sabatini, David M. Gray, Nathanael S. BE Weichhart, T TI Development of ATP-Competitive mTOR Inhibitors SO MTOR: METHODS AND PROTOCOLS SE Methods in Molecular Biology LA English DT Article; Book Chapter DE mTOR; mTORC1; mTORC2; PI3K; PIKK; Akt; Rapamycin; Torin 1 ID MAMMALIAN TARGET; SIGNALING NETWORK; RAPAMYCIN MTOR; CANCER; 3-KINASE AB The mammalian Target of Rapamycin (mTOR)-mediated signaling transduction pathway has been observed to be deregulated in a wide variety of cancer and metabolic diseases. Despite extensive clinical development efforts, the well-known allosteric mTOR inhibitor rapamycin and structurally related rapalogs have failed to show significant single-agent antitumor efficacy in most types of cancer. This limited clinical success may be due to the inability of the rapalogs to maintain a complete blockade mTOR-mediated signaling. Therefore, numerous efforts have been initiated to develop ATP-competitive mTOR inhibitors that would block both mTORC1 and mTORC2 complex activity. Here, we describe our experimental approaches to develop Torin1 using a medium throughput cell-based screening assay and structure-guided drug design. C1 [Liu, Qingsong; Thoreen, Carson C.; Hur, Wooyoung; Wang, Jinhua; Chang, Jae Won; Zhang, Jianming; Sim, Taebo; Gray, Nathanael S.] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. [Liu, Qingsong; Thoreen, Carson C.; Hur, Wooyoung; Wang, Jinhua; Chang, Jae Won; Zhang, Jianming; Sim, Taebo; Gray, Nathanael S.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [Kang, Seong A.; Markhard, Andrew; Sabatini, David M.] Whitehead Inst Biomed Res, Cambridge, MA 02142 USA. [Sabatini, David M.] MIT, Dept Biol, Howard Hughes Med Inst, Cambridge, MA USA. [Sabatini, David M.] MIT, Koch Ctr Integrat Canc Res, Cambridge, MA 02139 USA. RP Liu, QS (reprint author), Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. OI liu, qing song/0000-0002-7829-2547 FU NCI NIH HHS [R01 CA103866, R01 CA129105]; NIAID NIH HHS [R01 AI047389] NR 19 TC 12 Z9 12 U1 0 U2 2 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-61779-429-2 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2012 VL 821 BP 447 EP 460 DI 10.1007/978-1-61779-430-8_29 D2 10.1007/978-1-61779-430-8 PG 14 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BYN18 UT WOS:000299398200029 PM 22125084 ER PT J AU Liu, J Hu, Y Waller, DL Wang, JF Liu, QS AF Liu, Jing Hu, Yi Waller, David L. Wang, Junfeng Liu, Qingsong TI Natural products as kinase inhibitors SO NATURAL PRODUCT REPORTS LA English DT Review ID CYCLIN-DEPENDENT KINASES; RECEPTOR TYROSINE KINASE; OKINAWAN MARINE SPONGE; HUMAN PROSTATE-CANCER; ROUS-SARCOMA VIRUS; KAPPA-B KINASE; TRANSFORMING GENE-PRODUCT; RESORCYLIC ACID LACTONE; STREPTOMYCES SP KY11783; CELLS IN-VITRO AB Natural products have been widely used to dissect the basic mechanisms of fundamental life science and as clinical therapeutics. Recently, there has been significant interest in discovering new chemical pharmacophores in natural products to fulfil the vast demand for novel kinase inhibitors and address critical unmet medical needs with respect to signal transduction pathways. In this review, we summarize the history of several different classes of natural product-derived kinase inhibitors, discuss their kinome-wide target profiles and examine their structural binding modes based on available 3D X-ray structures. In particular, their origin, target activity, selectivity, scope and potential therapeutic development are highlighted against the backdrop of medicinal chemistry. C1 [Liu, Jing; Wang, Junfeng; Liu, Qingsong] Chinese Acad Sci, High Magnet Field Lab, Hefei 230031, Anhui, Peoples R China. [Liu, Jing] Harvard Univ, Dept Cell Biol, Sch Med, Boston, MA 02115 USA. [Hu, Yi] Harvard Univ, Ctr Neurol Dis, Sch Med, Cambridge, MA 02139 USA. [Hu, Yi] Brigham & Womens Hosp, Cambridge, MA 02139 USA. [Waller, David L.; Liu, Qingsong] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. [Waller, David L.; Liu, Qingsong] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. RP Liu, QS (reprint author), Chinese Acad Sci, High Magnet Field Lab, POB 1110, Hefei 230031, Anhui, Peoples R China. EM qsliu97@hmfl.ac.cn OI liu, qing song/0000-0002-7829-2547 NR 134 TC 22 Z9 23 U1 1 U2 35 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 0265-0568 J9 NAT PROD REP JI Nat. Prod. Rep. PY 2012 VL 29 IS 3 BP 392 EP 403 DI 10.1039/c2np00097k PG 12 WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Chemistry, Organic SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry GA 891YB UT WOS:000300251800004 PM 22231144 ER PT J AU Rosand, J Sheth, KN AF Rosand, Jonathan Sheth, Kevin N. TI Cutting Edge of Neurocritical Care SO NEUROTHERAPEUTICS LA English DT Editorial Material ID MORTALITY C1 [Rosand, Jonathan] Massachusetts Gen Hosp, Ctr Human Genet Res, Div Neurocrit Care & Emergency Neurol, Stroke Serv, Boston, MA 02114 USA. [Sheth, Kevin N.] Shock Trauma & Anesthesiol Res STAR Ctr, Div Stroke & Neurocrit Care, Dept Neurol, Boston, MA USA. [Sheth, Kevin N.] Shock Trauma & Anesthesiol Res STAR Ctr, Div Stroke & Neurocrit Care, Dept Neurosurg, Boston, MA USA. Shock Trauma & Anesthesiol Res STAR Ctr, Div Stroke & Neurocrit Care, Dept Surg, Boston, MA USA. [Sheth, Kevin N.] Shock Trauma & Anesthesiol Res STAR Ctr, Div Stroke & Neurocrit Care, Dept Anesthesiol, Boston, MA USA. [Sheth, Kevin N.] Shock Trauma & Anesthesiol Res STAR Ctr, Div Stroke & Neurocrit Care, Dept Emergency Med, Boston, MA USA. [Sheth, Kevin N.] Univ Maryland, Sch Med, R Adams Cowley Shock Trauma Ctr, Baltimore, MD 21201 USA. RP Rosand, J (reprint author), Massachusetts Gen Hosp, Ctr Human Genet Res, Div Neurocrit Care & Emergency Neurol, Stroke Serv, Boston, MA 02114 USA. EM jrosand@partners.org; KSheth@som.umaryland.edu NR 3 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1933-7213 J9 NEUROTHERAPEUTICS JI Neurotherapeutics PD JAN PY 2012 VL 9 IS 1 BP 1 EP 2 DI 10.1007/s13311-011-0099-0 PG 2 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA 891AG UT WOS:000300187900001 PM 22234456 ER PT J AU Murphy, S AF Murphy, Sarah TI Pediatric Neurocritical Care SO NEUROTHERAPEUTICS LA English DT Review DE Pediatric neurocritical care; Children; Pediatric TBI; Childhood stroke; Neuroprotection; Nonconvulsive seizures ID TRAUMATIC BRAIN-INJURY; ARTERIAL ISCHEMIC-STROKE; EXTRACORPOREAL MEMBRANE-OXYGENATION; CEREBRAL PERFUSION-PRESSURE; SEVERE HEAD-INJURY; NONCONVULSIVE STATUS EPILEPTICUS; EARLY DECOMPRESSIVE CRANIECTOMY; SINGLE-CENTER EXPERIENCE; HOSPITAL CARDIAC-ARREST; LENGTH-OF-STAY AB Pediatric neurocritical care is an emerging multidisciplinary field of medicine and a new frontier in pediatric critical care and pediatric neurology. Central to pediatric neurocritical care is the goal of improving outcomes in critically ill pediatric patients with neurological illness or injury and limiting secondary brain injury through optimal critical care delivery and the support of brain function. There is a pressing need for evidence based guidelines in pediatric neurocritical care, notably in pediatric traumatic brain injury and pediatric stroke. These diseases have distinct clinical and pathophysiological features that distinguish them from their adult counterparts and prevent the direct translation of the adult experience to pediatric patients. Increased attention is also being paid to the broader application of neuromonitoring and neuroprotective strategies in the pediatric intensive care unit, in both primary neurological and primary non-neurological disease states. Although much can be learned from the adult experience, there are important differences in the critically ill pediatric population and in the circumstances that surround the emergence of neurocritical care in pediatrics. C1 [Murphy, Sarah] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Murphy, Sarah] MassGen Hosp Children, Boston, MA 02114 USA. RP Murphy, S (reprint author), Harvard Univ, Sch Med, Boston, MA 02114 USA. EM samurphy@partners.org NR 194 TC 9 Z9 9 U1 2 U2 5 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1933-7213 J9 NEUROTHERAPEUTICS JI Neurotherapeutics PD JAN PY 2012 VL 9 IS 1 BP 3 EP 16 DI 10.1007/s13311-011-0093-6 PG 14 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA 891AG UT WOS:000300187900002 PM 22183817 ER PT J AU Kimberly, WT AF Kimberly, W. Taylor TI Biomarkers in Neurocritical Care SO NEUROTHERAPEUTICS LA English DT Review DE Neurocritical care; Biomarker; Surrogate endpoint; Neuroimaging; Intracranial monitor ID TRAUMATIC BRAIN-INJURY; SEVERE HEAD-INJURY; TISSUE-PLASMINOGEN ACTIVATOR; ANEURYSMAL SUBARACHNOID HEMORRHAGE; ACUTE ISCHEMIC-STROKE; INTRA-CRANICAL PRESSURE; MIDDLE CEREBRAL-ARTERY; DIGITAL-SUBTRACTION-ANGIOGRAPHY; ACUTE INTRACEREBRAL HEMORRHAGE; COMPUTED-TOMOGRAPHY FINDINGS AB The gold standard for assessing neurological function is the bedside clinical examination. However, in neurocritical patients, the signs and symptoms related to the severity of illness can often be ambiguous. It can be hard to distinguish between a severe but stable disease state and one that is dynamic and in a critical decline. Clinicians and family members alike may struggle with the uncertainty of functional outcome prediction. Intermediate biomarkers of brain injury can assist with ongoing clinical management of patients, and in some circumstances can guide prognosis. Used in the right setting, biomarkers in neurocritical care can also aid with decisions to intensify treatment or avoid prolonged and unnecessary therapy. The term biomarker is used in various ways, and here we use it to refer to 3 general types: 1) circulating blood macromolecules, 2) brain imaging, and 3) continuous invasive monitors. Despite its promise, biomarkers have several limitations and should be interpreted in the context of the overall clinical assessment. C1 Massachusetts Gen Hosp, Div Neurocrit Care & Emergency Neurol, Dept Neurol, Boston, MA 02114 USA. RP Kimberly, WT (reprint author), Massachusetts Gen Hosp, Div Neurocrit Care & Emergency Neurol, Dept Neurol, Boston, MA 02114 USA. EM wtkimberly@partners.org FU National Institutes of Health [1K23NS076597]; Beth Israel Deaconess Medical Center, Harvard Medical School; Pfizer Inc.; Merck Co. FX This work was supported by the National Institutes of Health (No. 1K23NS076597) and a grant from the Clinical Investigator Training Program: Beth Israel Deaconess Medical Center, Harvard Medical School, in collaboration with Pfizer Inc. and Merck & Co. NR 79 TC 3 Z9 3 U1 0 U2 5 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1933-7213 J9 NEUROTHERAPEUTICS JI Neurotherapeutics PD JAN PY 2012 VL 9 IS 1 BP 17 EP 23 DI 10.1007/s13311-011-0089-2 PG 7 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA 891AG UT WOS:000300187900003 PM 22105793 ER PT J AU Rosenthal, ES AF Rosenthal, Eric S. TI The Utility of EEG, SSEP, and Other Neurophysiologic Tools to Guide Neurocritical Care SO NEUROTHERAPEUTICS LA English DT Review DE Seizures; Critical care; Evoked potentials; Electroencephalography; Physiologic monitoring; Stroke; Cerebral hemorrhage; Traumatic brain injury; Subarachnoid hemorrhage ID TRAUMATIC BRAIN-INJURY; NONCONVULSIVE STATUS EPILEPTICUS; SOMATOSENSORY-EVOKED-POTENTIALS; REFRACTORY STATUS EPILEPTICUS; CONVULSIVE STATUS EPILEPTICUS; NEURON-SPECIFIC ENOLASE; CORTICAL SPREADING DEPRESSION; GRADE SUBARACHNOID HEMORRHAGE; NEAR-INFRARED SPECTROSCOPY; DELAYED CEREBRAL-ISCHEMIA AB Neuromonitoring is an emerging field that aims to characterize real-time neurophysiology to tailor therapy for acute injuries of the central nervous system. While cardiac telemetry has been used for decades among patients requiring critical care of all kinds, neurophysiology and neurotelemetry has only recently emerged as a routine screening tool in comatose patients. The increasing utilization of electroencephalography in comatose patients is primarily due to the recognition of the common occurrence of nonconvulsive seizures among comatose patients, the development of quantitative measures to detect regional ischemia, and the appreciation of electroencephalography phenotypes that indicate prognosis after cardiac arrest. Other neuromonitoring tools, such as somatosensory evoked potentials have a complementary role, surveying the integrity of the neuroaxis as an indicator of prognosis or illness progression in both acute brain and spinal injuries. C1 Massachusetts Gen Hosp, Dept Neurol, Div Neurocrit Care & Emergency Neurol, Boston, MA 02114 USA. RP Rosenthal, ES (reprint author), Massachusetts Gen Hosp, Dept Neurol, Div Neurocrit Care & Emergency Neurol, 55 Fruit St, Boston, MA 02114 USA. EM erosenthal@partners.org OI Rosenthal, Eric/0000-0003-3900-356X NR 132 TC 6 Z9 6 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1933-7213 J9 NEUROTHERAPEUTICS JI Neurotherapeutics PD JAN PY 2012 VL 9 IS 1 BP 24 EP 36 DI 10.1007/s13311-011-0101-x PG 13 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA 891AG UT WOS:000300187900004 PM 22234455 ER PT J AU Walcott, BP Kahle, KT Simard, JM AF Walcott, Brian P. Kahle, Kristopher T. Simard, J. Marc TI Novel Treatment Targets for Cerebral Edema SO NEUROTHERAPEUTICS LA English DT Review DE Cerebral edema; Hyponatraemia; Osmotherapy; NKCC1; SUR1/TRPM4; Vaptan; Glyburide ID TRAUMATIC BRAIN-INJURY; K+-CL-COTRANSPORTER; ANEURYSMAL SUBARACHNOID HEMORRHAGE; EXPERIMENTAL INTRACEREBRAL HEMORRHAGE; ELEVATED INTRACRANIAL-PRESSURE; BARRIER PERMEABILITY INCREASE; NONSELECTIVE CATION CHANNEL; ADULT-RAT BRAIN; HYPERTONIC SALINE; VASOPRESSIN ANTAGONISTS AB Cerebral edema is a common finding in a variety of neurological conditions, including ischemic stroke, traumatic brain injury, ruptured cerebral aneurysm, and neoplasia. With the possible exception of neoplasia, most pathological processes leading to edema seem to share similar molecular mechanisms of edema formation. Challenges to brain-cell volume homeostasis can have dramatic consequences, given the fixed volume of the rigid skull and the effect of swelling on secondary neuronal injury. With even small changes in cellular and extracellular volume, cerebral edema can compromise regional or global cerebral blood flow and metabolism or result in compression of vital brain structures. Osmotherapy has been the mainstay of pharmacologic therapy and is typically administered as part of an escalating medical treatment algorithm that can include corticosteroids, diuretics, and pharmacological cerebral metabolic suppression. Novel treatment targets for cerebral edema include the Na(+)-K(+)-2Cl(-) co-transporter (NKCC1) and the SUR1-regulated NCCa-ATP (SUR1/TRPM4) channel. These two ion channels have been demonstrated to be critical mediators of edema formation in brain-injured states. Their specific inhibitors, bumetanide and glibenclamide, respectively, are well-characterized Food and Drug Administration-approved drugs with excellent safety profiles. Directed inhibition of these ion transporters has the potential to reduce the development of cerebral edema and is currently being investigated in human clinical trials. Another class of treatment agents for cerebral edema is vasopressin receptor antagonists. Euvolemic hyponatremia is present in a myriad of neurological conditions resulting in cerebral edema. A specific antagonist of the vasopressin V1A- and V2-receptor, conivaptan, promotes water excretion while sparing electrolytes through a process known as aquaresis. C1 [Simard, J. Marc] Univ Maryland, Sch Med, Dept Neurosurg, Baltimore, MD 21201 USA. [Walcott, Brian P.; Kahle, Kristopher T.] Harvard Univ, Sch Med, Dept Neurosurg, Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Simard, JM (reprint author), Univ Maryland, Sch Med, Dept Neurosurg, Baltimore, MD 21201 USA. EM MSimard@smail.umaryland.edu FU Department of Veterans Affairs (Baltimore, MD); National Heart, Lung and Blood Institute [HL082517]; National Institute of Neurological Disorders and Stroke [NS061808, NS060801] FX This work was supported in part by grants from the Department of Veterans Affairs (Baltimore, MD to J.M.S.); the National Heart, Lung and Blood Institute (HL082517 to J.M.S.), and the National Institute of Neurological Disorders and Stroke (NS061808, NS060801 to J.M.S.). NR 99 TC 43 Z9 46 U1 3 U2 13 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1933-7213 J9 NEUROTHERAPEUTICS JI Neurotherapeutics PD JAN PY 2012 VL 9 IS 1 BP 65 EP 72 DI 10.1007/s13311-011-0087-4 PG 8 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA 891AG UT WOS:000300187900008 PM 22125096 ER PT J AU Brouwers, HB Goldstein, JN AF Brouwers, H. Bart Goldstein, Joshua N. TI Therapeutic Strategies in Acute Intracerebral Hemorrhage SO NEUROTHERAPEUTICS LA English DT Review DE Intracerebral hemorrhage; Diagnosis; Treatment; Blood pressure; Anticoagulation; Surgery ID PROTHROMBIN COMPLEX CONCENTRATE; ANGIOGRAPHY SPOT SIGN; ACTIVATED FACTOR-VII; PREDICTS HEMATOMA EXPANSION; RANDOMIZED CONTROLLED-TRIAL; ORAL ANTICOAGULANT-THERAPY; ACUTE CEREBRAL-HEMORRHAGE; CT ANGIOGRAPHY; BLOOD-PRESSURE; INTRAVENTRICULAR HEMORRHAGE AB Intracerebral hemorrhage is a devastating disease, and no specific therapy has been proven to reduce mortality in a randomized controlled trial. However, management in a neuroscience intensive care unit does appear to improve outcomes, suggesting that many available therapies do in fact provide benefit. In the acute phase of intracerebral hemorrhage care, strategies aimed at minimizing ongoing bleeding include reversal of anticoagulation and modest blood pressure reduction. In addition, the monitoring and regulation of glucose levels, temperature, and, in selected cases, intracranial pressure are recommended by many groups. Selected patients may benefit from hematoma evacuation or external ventricular drainage. Ongoing clinical trials are examining aggressive blood pressure management, hemostatic therapy, platelet transfusion, stereotactic hematoma evacuation, and intraventricular thrombolysis. Finally, preventing recurrence of intracerebral hemorrhage is of pivotal importance, and tight blood pressure management is paramount. C1 [Brouwers, H. Bart] Massachusetts Gen Hosp, J Philip Kistler Stroke Res Ctr, Boston, MA 02114 USA. [Brouwers, H. Bart; Goldstein, Joshua N.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol,Div Neurocrit Care & Emergency Neurol, Boston, MA 02114 USA. [Brouwers, H. Bart] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Goldstein, Joshua N.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. RP Brouwers, HB (reprint author), Massachusetts Gen Hosp, J Philip Kistler Stroke Res Ctr, 175 Cambridge St,Suite 300, Boston, MA 02114 USA. EM brouwers@chgr.mgh.harvard.edu RI Goldstein, Joshua/H-8953-2016 FU National Institutes of Health (NIH) - National Institute of Neurological Disorders and Stroke (NINDS) [5K23NS059774, P50NS051343] FX All funding entities had no involvement in study design, data collection and interpretation, writing of the manuscript and decision to submit it for publication. The study was funded by the National Institutes of Health (NIH) - National Institute of Neurological Disorders and Stroke (NINDS) grant No. 5K23NS059774. Dr. Brouwers was supported by the NIH - NINDS Specialized Program of Translational Research in Acute Stroke (SPOTRIAS) fellowship grant No. P50NS051343. NR 134 TC 14 Z9 18 U1 2 U2 5 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1933-7213 EI 1878-7479 J9 NEUROTHERAPEUTICS JI Neurotherapeutics PD JAN PY 2012 VL 9 IS 1 BP 87 EP 98 DI 10.1007/s13311-011-0091-8 PG 12 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA 891AG UT WOS:000300187900010 PM 22139592 ER PT J AU Ho, L Varghese, M Wang, J Zhao, W Chen, F Knable, LA Ferruzzi, M Pasinetti, GM AF Ho, Lap Varghese, Merina Wang, Jun Zhao, Wei Chen, Fei Knable, Lindsay Alexis Ferruzzi, Mario Pasinetti, Giulio M. TI Dietary supplementation with decaffeinated green coffee improves diet-induced insulin resistance and brain energy metabolism in mice SO NUTRITIONAL NEUROSCIENCE LA English DT Article DE Alzheimer's disease; Dementia; Mitochondria; Chlorogenic acid; Coffee ID CHLOROGENIC ACID; ALZHEIMERS-DISEASE; BODY-WEIGHT; HUMANS; CONSUMPTION; RISK; TEA; CAFFEINE; OBESITY AB Objectives: There is accumulating evidence that coffee consumption may reduce risk for type 2 diabetes, a known risk factor for Alzheimer's and other neurological diseases. Coffee consumption is also associated with reduced risk for Alzheimer's disease and non-Alzheimer's dementias. However, preventive and therapeutic development of coffee is complicated by the cardiovascular side effects of caffeine intake. As coffee is also a rich source of chlorogenic acids and many bioactive compounds other than caffeine, we hypothesized that decaffeinated coffee drinks may exert beneficial effects on the brain. Methods: We have investigated whether dietary supplementation with a standardized decaffeinated green coffee preparation, Svetol (R), might modulate diet-induced insulin resistance and brain energy metabolism dysfunction in a high-fat diet mouse model. Results: As expected, dietary supplementation with Svetol (R) significantly attenuated the development of high-fat diet-induced deficits in glucose-tolerance response. We have also found that Svetol (R) treatment improved brain mitochondrial energy metabolism as determined by oxygen consumption rate. Consistent with this evidence, follow-up gene expression profiling with Agilent whole-genome microarray revealed that the decaffeinated coffee treatment modulated a number of genes in the brain that are implicated in cellular energy metabolism. Discussion: Our evidence is the first demonstration that dietary supplementation with a decaffeinated green coffee preparation may beneficially influence the brain, in particular promoting brain energy metabolic processes. C1 [Ho, Lap; Varghese, Merina; Wang, Jun; Zhao, Wei; Chen, Fei; Knable, Lindsay Alexis; Pasinetti, Giulio M.] Mt Sinai Sch Med, Dept Neurol, New York, NY 10029 USA. [Ferruzzi, Mario] Purdue Univ, Dept Food Sci, W Lafayette, IN 47907 USA. [Ferruzzi, Mario] Purdue Univ, Dept Foods & Nutr, W Lafayette, IN 47907 USA. [Pasinetti, Giulio M.] Mt Sinai Sch Med, Dept Psychiat, New York, NY 10029 USA. [Pasinetti, Giulio M.] Mt Sinai Sch Med, Dept Neurosci, New York, NY 10029 USA. [Pasinetti, Giulio M.] James J Peters Vet Affairs Med Ctr, Geriatr Res Educ & Clin Ctr, Bronx, NY USA. RP Pasinetti, GM (reprint author), Mt Sinai Sch Med, Dept Neurol, Annenberg Bldg,Room 20-06,1468 Madison Ave & 100, New York, NY 10029 USA. EM giulio.pasinetti@mssm.edu OI Varghese, Merina/0000-0002-1517-3903 NR 28 TC 16 Z9 16 U1 2 U2 16 PU MANEY PUBLISHING PI LEEDS PA STE 1C, JOSEPHS WELL, HANOVER WALK, LEEDS LS3 1AB, W YORKS, ENGLAND SN 1028-415X J9 NUTR NEUROSCI JI Nutr. Neurosci. PD JAN PY 2012 VL 15 IS 1 BP 37 EP 45 DI 10.1179/1476830511Y.0000000027 PG 9 WC Neurosciences; Nutrition & Dietetics SC Neurosciences & Neurology; Nutrition & Dietetics GA 894HE UT WOS:000300416900006 PM 22305652 ER PT J AU Yaffe, K Laffan, AM Harrison, SL Redline, S Spira, AP Ensrud, KE Ancoli-Israel, S Stone, KL AF Yaffe, Kristine Laffan, Alison M. Harrison, Stephanie Litwack Redline, Susan Spira, Adam P. Ensrud, Kristine E. Ancoli-Israel, Sonia Stone, Katie L. TI Sleep-Disordered Breathing, Hypoxia, and Risk of Mild Cognitive Impairment and Dementia in Older Women EDITORIAL COMMENT SO OBSTETRICAL & GYNECOLOGICAL SURVEY LA English DT Editorial Material AB Up to 60% of older adults have sleep-disordered breathing, a disorder characterized by recurrent arousals from sleep and intermittent hypoxemia. Cognitive impairment is also common in older populations. Several cross-sectional studies have reported an association between sleep-disordered breathing and poor cognition. However, other studies have found no association, and the majority of studies showing an association had deficiencies in design and methodology. Therefore, it is unclear whether sleep-disordered breathing precedes impaired cognition in the elderly population. The present investigation, a substudy of the Study of Osteoporotic Fractures, was designed to determine prospectively whether sleep-disordered breathing is associated with mild cognitive impairment and dementia, increasing the risk of its development 5 years later. Potential mechanisms (hypoxia, sleep fragmentation, and sleep duration) to explain a positive association with cognitive dysfunction were also investigated. Sleep-disordered breathing was measured objectively with overnight polysomnography in 298 women without dementia (mean age: 82.3 years) from 2002 to 2004. The apnea-hypopnea index (the number of apnea plus hypopnea events per hour of sleep) was determined. Sleep-disordered breathing was defined as an index of 15 or more events per hour. Cognitive status (normal, dementia, or mild cognitive impairment) was determined in all participants between 2006 and 2008 at a mean follow-up of 4.7 years. Univariate and multivariate logistic regression models were used to examine the associations in women with (n = 105) and without (n = 193) dementia. Multivariate models were adjusted for potential confounders (demographic risk factors and comorbidities), including age, race, body mass index, educational attainment, smoking status, presence of diabetes or hypertension, use of medication (antidepressants, benzodiazepines, or nonbenzodiazepine anxiolytics), and baseline cognitive scores. Of the 298 women in the analysis, 105 (35.2%) had sleep-disordered breathing. The affected women were more likely to develop mild cognitive impairment or dementia than women without sleep-disordered breathing (44.8% vs. 31.1%); the adjusted odds ratio (aOR) was 1.85, with a 95% confidence interval (CI) of 1.11-3.08 (P = 0.02). A higher incidence of mild cognitive impairment or dementia was found for 2 measures of apnea or hypopnea: an oxygen desaturation index: >= 15 (aOR, 1.71; 95% CI, 1.04-2.83) and a high percentage of total sleep time (>7%) (aOR, 2.04; 95% CI, 1.10-3.78). No significant association in the adjusted data was observed for the sleep fragmentation or sleep duration measures. These findings suggest that older women with sleep-disordered breathing are at increased risk of developing cognitive impairment 5 years later compared with those without sleep-disordered breathing. C1 [Yaffe, Kristine] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94143 USA. [Yaffe, Kristine] Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94143 USA. [Yaffe, Kristine] Univ Calif San Francisco, Dept Epidemiol, San Francisco, CA 94143 USA. [Yaffe, Kristine] San Francisco VA Med Ctr, San Francisco, CA USA. [Laffan, Alison M.; Harrison, Stephanie Litwack; Stone, Katie L.] Calif Pacific Med Ctr, San Francisco Coordinating Ctr, San Francisco, CA USA. [Redline, Susan] Brigham & Womens Hosp, Div Sleep Med, Boston, MA 02115 USA. [Redline, Susan] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Boston, MA 02215 USA. [Spira, Adam P.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Mental Hlth, Baltimore, MD USA. [Ensrud, Kristine E.] Univ Minnesota, Dept Med, Minneapolis, MN 55455 USA. [Ensrud, Kristine E.] Univ Minnesota, Dept Epidemiol, Minneapolis, MN USA. [Ensrud, Kristine E.] Univ Minnesota, Dept Community Hlth, Minneapolis, MN USA. [Ensrud, Kristine E.] Vet Affairs Med Ctr, Minneapolis, MN USA. [Ancoli-Israel, Sonia] Univ Calif San Diego, Dept Psychiat, San Diego, CA 92103 USA. RP Yaffe, K (reprint author), Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94143 USA. NR 0 TC 0 Z9 0 U1 3 U2 11 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0029-7828 J9 OBSTET GYNECOL SURV JI Obstet. Gynecol. Surv. PD JAN PY 2012 VL 67 IS 1 BP 34 EP 36 DI 10.1097/OGX.0b013e3182439f33 PG 3 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 891MD UT WOS:000300220300016 ER PT J AU Sun, L Yao, Y Liu, B Lin, Z Lin, L Yang, M Zhang, W Chen, W Pan, C Liu, Q Song, E Li, J AF Sun, L. Yao, Y. Liu, B. Lin, Z. Lin, L. Yang, M. Zhang, W. Chen, W. Pan, C. Liu, Q. Song, E. Li, J. TI MiR-200b and miR-15b regulate chemotherapy-induced epithelial-mesenchymal transition in human tongue cancer cells by targeting BMI1 SO ONCOGENE LA English DT Article DE chemotherapy resistance; EMT; microRNA; BMI1; tongue squamous cell carcinoma ID BREAST-CANCER; TAMOXIFEN RESISTANCE; MULTIDRUG-RESISTANCE; SIGNALING PATHWAY; SELF-RENEWAL; MICRORNAS; EXPRESSION; APOPTOSIS; CHEMORESISTANCE; TUMORIGENICITY AB Chemotherapy has been reported to induce epithelial-mesenchymal transition (EMT) in tumor cells, which is a critical step in the process of metastasis leading to cancer spreading and treatment failure. However, the underlying mechanisms of chemotherapy-induced EMT remain unclear, and the involvement of microRNAs (miRNA) in this process is poorly understood. To address these questions, we established stable chemotherapy-resistant tongue squamous cell carcinoma (TSCC) cell lines CAL27-res and SCC25-res by exposing the parental CAL27 and SCC25 lines to escalating concentrations of cisplatin for 6 months. CAL27-res and SCC25-res cells displayed mesenchymal features with enhanced invasiveness and motility. MiRNA microarray illustrated that miR-200b and miR-15b were the most significantly downregulated microRNAs in CAL27-res cells. Ectopic expression of miR-200b and miR-15b with miRNA mimics effectively reversed the phenotype of EMT in CAL27-res and SCC25-res cells, and sensitized them to chemotherapy, but inhibition of miR-200b and miR-15b in the sensitive lines with anti-sense oligonucleotides induced EMT and conferred chemoresistance. Retrieving the expression of B lymphoma Mo-MLV insertion region 1 homolog (BMI1), a target for miR-200b and miR-15b, in the presence of the miRNA mimics by transfecting CAL27-res cells with pcDNA3.1-BMI1-carrying mutated seed sequences of miR-200b or miR-15b at its 3'-UTR recapitulated chemotherapy-induced EMT. In vivo, enforced miR-200b or miR-15b expression suppressed metastasis of TSCC xenografts established by CAL27-res cells. Clinically, reduced miR-200b or miR-15b expression was associated with chemotherapeutic resistance in TSCCs and poor patient survival. Our data suggest that reduced expression of miR-200b and miR-15b underscores the mechanisms of chemotherapy-induced EMT in TSCC, and may serve as therapeutic targets to reverse chemotherapy resistance in tongue cancers. Oncogene (2012) 31, 432-445; doi: 10.1038/onc.2011.263; published online 4 July 2011 C1 [Sun, L.; Yao, Y.; Liu, B.; Lin, L.; Yang, M.; Song, E.] Sun Yat Sen Univ, Dept Breast Tumor Ctr, Sun Yat Sen Mem Hosp, Guangzhou 510275, Guangdong, Peoples R China. [Lin, Z.; Zhang, W.; Chen, W.; Pan, C.; Li, J.] Sun Yat Sen Univ, Dept Oral & Maxillofacial Surg, Sun Yat Sen Mem Hosp, Guangzhou 510275, Guangdong, Peoples R China. [Liu, Q.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Song, E.] Sun Yat Sen Univ, Key Lab Gene Engn, Minist Educ, State Key Lab Biocontrol,Sch Life Sci, Guangzhou 510275, Guangdong, Peoples R China. RP Song, E (reprint author), Sun Yat Sen Univ, Breast Tumor Ctr, Sun Yat Sen Mem Hosp, 107 Yanjiang W Rd, Gz 510120, Peoples R China. EM songerwei02@yahoo.com.cn; lijinsong1967@163.com RI Liu, Bodu/G-5222-2016 OI Liu, Bodu/0000-0003-2097-725X FU National Natural Science Foundation of China [81072225, 30921140312, 30831160515, 30830110, 81072177]; Natural Science Foundation of Guangdong Province [10251008901000022, 9151008901000201, 8251008901000011]; Guangzhou Science and Technology Bureau [2008Z1-E201]; Ministry of Science and Technology of China [2010CB912800, 2011CB504203, 2009CB521706]; Key Laboratory of malignant tumor gene regulation and target therapy of Guangdong Higher Education Institutes, Sun Yat-sen University [KLB09001] FX This work was supported by Grants to JL from National Natural Science Foundation of China (81072225), Natural Science Foundation of Guangdong Province (10251008901000022, 9151008901000201) and Guangzhou Science and Technology Bureau (2008Z1-E201); and to ES from '973' Program Projects (2010CB912800, 2011CB504203, 2009CB521706) from Ministry of Science and Technology of China, National Natural Science Foundation of China (30921140312, 30831160515, 30830110), and Natural Science Foundation of Guangdong Province (8251008901000011), Key Laboratory of malignant tumor gene regulation and target therapy of Guangdong Higher Education Institutes, Sun Yat-sen University (KLB09001), and to LL from National Natural Science Foundation of China (81072177). NR 43 TC 101 Z9 107 U1 5 U2 34 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD JAN PY 2012 VL 31 IS 4 BP 432 EP 445 DI 10.1038/onc.2011.263 PG 14 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 891LU UT WOS:000300219300003 PM 21725369 ER PT S AU Hasturk, H Kantarci, A Van Dyke, TE AF Hasturk, Hatice Kantarci, Alpdogan Van Dyke, Thomas E. BE Kinane, DF Mombelli, A TI Paradigm Shift in the Pharmacological Management of Periodontal Diseases SO PERIODONTAL DISEASE SE Frontiers of Oral Biology LA English DT Article; Book Chapter ID NONSTEROIDAL ANTIINFLAMMATORY DRUGS; POLYUNSATURATED FATTY-ACIDS; A(4) STABLE ANALOGS; LIPOXIN A(4); DOCOSAHEXAENOIC ACID; ANTI-INFLAMMATION; CYCLOOXYGENASE-2 INHIBITORS; JUVENILE PERIODONTITIS; CARDIOVASCULAR-DISEASE; ISCHEMIA-REPERFUSION AB It is becoming clear that variations in inflammatory response are a major determinant in susceptibility to periodontitis. However, our understanding of the relationship of the causal agents in periodontitis to the pathogenesis is not as clear as we once thought, and thus therapies based on etiopathogenesis are similarly in question. We are entering a new era of therapeutic discovery that may have a major impact on our management of the periodontal diseases. Fundamentally, periodontitis is an irreversible condition and once both soft and hard tissues are lost, the healthy periodontal architecture cannot be completely or predictably rebuilt. The discovery of new families of lipid mediators of resolution of inflammation (the lipoxins) and eicosapentaenoic-acid- and docosahexaenoic-acid-derived chemical mediators (the resolvins and protectins) opens new avenues to designing resolution-targeted therapies to control the unwanted side effects of excessive inflammation. The novel protective and therapeutic actions of pro-resolution lipid mediators following microbial challenge are mediated by regulation of the local and systemic inflammatory response that has a direct impact on the organization of the biofilm (plaque) and suggests a new paradigm in clinical periodontal therapeutics. Copyright (C) 2012 S. Karger AG, Basel C1 [Hasturk, Hatice; Kantarci, Alpdogan; Van Dyke, Thomas E.] Forsyth Inst, Dept Periodontol, Cambridge, MA 02142 USA. RP Hasturk, H (reprint author), Forsyth Inst, Dept Periodontol, Suite 1757,245 1st St, Cambridge, MA 02142 USA. EM hhasturk@forsyth.org FU NIDCR NIH HHS [DE16191, DE19938, P50 DE016191, R01 DE015566, R01 DE019938, DE15566, K23 DE018917] NR 113 TC 24 Z9 26 U1 0 U2 1 PU KARGER PI BASEL PA POSTFACH, CH-4009 BASEL, SWITZERLAND SN 1420-2433 BN 978-3-8055-9833-0 J9 FRONT ORAL BIOL JI Front. Oral Biol. PY 2012 VL 15 BP 160 EP 176 PG 17 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA BYN41 UT WOS:000299437600011 PM 22142963 ER PT J AU Carmena, M Pinson, X Platani, M Salloum, Z Xu, ZJ Clark, A MacIsaac, F Ogawa, H Eggert, U Glover, DM Archambault, V Earnshaw, WC AF Carmena, Mar Pinson, Xavier Platani, Melpi Salloum, Zeina Xu, Zhenjie Clark, Anthony MacIsaac, Fiona Ogawa, Hiromi Eggert, Ulrike Glover, David M. Archambault, Vincent Earnshaw, William C. TI The Chromosomal Passenger Complex Activates Polo Kinase at Centromeres SO PLOS BIOLOGY LA English DT Article ID HISTONE H3 PHOSPHORYLATION; AURORA-B KINASE; TRCP-DEPENDENT DEGRADATION; INNER CENTROMERE; MITOTIC ENTRY; CENTRAL SPINDLE; PROTEIN INCENP; KINETOCHORE; MITOSIS; PLK1 AB The coordinated activities at centromeres of two key cell cycle kinases, Polo and Aurora B, are critical for ensuring that the two sister kinetochores of each chromosome are attached to microtubules from opposite spindle poles prior to chromosome segregation at anaphase. Initial attachments of chromosomes to the spindle involve random interactions between kinetochores and dynamic microtubules, and errors occur frequently during early stages of the process. The balance between microtubule binding and error correction (e.g., release of bound microtubules) requires the activities of Polo and Aurora B kinases, with Polo promoting stable attachments and Aurora B promoting detachment. Our study concerns the coordination of the activities of these two kinases in vivo. We show that INCENP, a key scaffolding subunit of the chromosomal passenger complex (CPC), which consists of Aurora B kinase, INCENP, Survivin, and Borealin/Dasra B, also interacts with Polo kinase in Drosophila cells. It was known that Aurora A/Bora activates Polo at centrosomes during late G2. However, the kinase that activates Polo on chromosomes for its critical functions at kinetochores was not known. We show here that Aurora B kinase phosphorylates Polo on its activation loop at the centromere in early mitosis. This phosphorylation requires both INCENP and Aurora B activity (but not Aurora A activity) and is critical for Polo function at kinetochores. Our results demonstrate clearly that Polo kinase is regulated differently at centrosomes and centromeres and suggest that INCENP acts as a platform for kinase crosstalk at the centromere. This crosstalk may enable Polo and Aurora B to achieve a balance wherein microtubule mis-attachments are corrected, but proper attachments are stabilized allowing proper chromosome segregation. C1 [Carmena, Mar; Platani, Melpi; Xu, Zhenjie; Clark, Anthony; MacIsaac, Fiona; Ogawa, Hiromi; Earnshaw, William C.] Univ Edinburgh, Wellcome Trust Ctr Cell Biol, Edinburgh, Midlothian, Scotland. [Pinson, Xavier; Salloum, Zeina; Archambault, Vincent] Univ Montreal, Inst Rech Immunol & Cancerol, Montreal, PQ, Canada. [Eggert, Ulrike] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Eggert, Ulrike] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [Glover, David M.] Univ Cambridge, Dept Genet, Cell Cycle Genet Res Grp, Canc Res UK, Cambridge CB2 3EH, England. [Archambault, Vincent] Univ Montreal, Dept Biochim, Montreal, PQ H3C 3J7, Canada. RP Carmena, M (reprint author), Univ Edinburgh, Wellcome Trust Ctr Cell Biol, Edinburgh, Midlothian, Scotland. EM mar.carmena@ed.ac.uk; vincent.archambault.1@umontreal.ca RI Xu, Zhenjie/A-6443-2014; OI Glover, David/0000-0003-0956-0103 FU Wellcome Trust [WCE 073915/Z/03/Z]; Wellcome Trust Centre for Cell Biology [077707, 092076]; Human Frontier Science Program Organization [CDA00036/2009]; Fonds de recherche en sante du Quebec; Canadian Institutes of Health Research; NIH [R01 GM082834] FX The WCE Lab is supported by Wellcome Trust Principal Research Fellowship to WCE 073915/Z/03/Z (The Wellcome Trust: http://www.wellcome.ac.uk/). The Wellcome Trust Centre for Cell Biology is funded by core grants number 077707 and 092076. VA Holds a Career Development Award from the Human Frontier Science Program Organization - CDA00036/2009 (www.hfspo.org) and a fellowship from the Fonds de recherche en sante du Quebec. Work in VA's lab was funded by the Canadian Institutes of Health Research (www.cihr-irsc.gc.ca). U.S.E. was supported by NIH grant R01 GM082834. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 54 TC 46 Z9 47 U1 0 U2 7 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1544-9173 J9 PLOS BIOL JI PLoS. Biol. PD JAN PY 2012 VL 10 IS 1 AR e1001250 DI 10.1371/journal.pbio.1001250 PG 15 WC Biochemistry & Molecular Biology; Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics GA 894IM UT WOS:000300420400019 PM 22291575 ER PT J AU Bass, JK Bornemann, TH Burkey, M Chehil, S Chen, L Copeland, JRM Eaton, WW Ganju, V Hayward, E Hock, RS Kidwai, R Kolappa, K Lee, PT Minas, H Or, F Raviola, GJ Saraceno, B Patel, V AF Bass, Judith K. Bornemann, Thomas H. Burkey, Matthew Chehil, Sonia Chen, Lenis Copeland, John R. M. Eaton, William W. Ganju, Vijay Hayward, Erin Hock, Rebecca S. Kidwai, Rubeena Kolappa, Kavitha Lee, Patrick T. Minas, Harry Or, Flora Raviola, Giuseppe J. Saraceno, Benedetto Patel, Vikram TI A United Nations General Assembly Special Session for Mental, Neurological, and Substance Use Disorders: The Time Has Come SO PLOS MEDICINE LA English DT Editorial Material ID RANDOMIZED CONTROLLED-TRIAL; MIDDLE-INCOME COUNTRIES; HEALTH; INTERVENTION; DEPRESSION C1 [Bass, Judith K.; Eaton, William W.; Hock, Rebecca S.; Kidwai, Rubeena; Or, Flora] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Mental Hlth, Baltimore, MD USA. [Bornemann, Thomas H.] Emory Univ, Carter Ctr, Mental Hlth Program, Atlanta, GA 30322 USA. [Burkey, Matthew] Johns Hopkins Univ Hosp, Dept Psychiat & Behav Sci, Baltimore, MD 21287 USA. [Chehil, Sonia] Dalhousie Univ, Div Child & Adolescent Psychiat, Halifax, NS, Canada. [Chen, Lenis] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Int Hlth, Baltimore, MD USA. [Copeland, John R. M.] Univ Liverpool, Div Psychiat, Liverpool L69 3BX, Merseyside, England. [Ganju, Vijay] World Federat Mental Hlth, Woodbridge, VA USA. [Hayward, Erin; Kolappa, Kavitha] Johns Hopkins Sch Med, Baltimore, MD USA. [Lee, Patrick T.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Minas, Harry] Univ Melbourne, Melbourne Sch Populat Hlth, Ctr Int Mental Hlth, Melbourne, Vic 3010, Australia. [Raviola, Giuseppe J.] Harvard Univ, Sch Med, Dept Global Hlth & Social Med, Program Global Mental Hlth & Social Change, Boston, MA USA. [Saraceno, Benedetto] Univ Geneva, Dept Psychiat, Geneva, Switzerland. [Saraceno, Benedetto] Global Initiat Psychiat, Hilversum, Netherlands. [Patel, Vikram] London Sch Hyg & Trop Med, Fac Epidemiol & Populat Hlth, London WC1, England. RP Bass, JK (reprint author), Johns Hopkins Bloomberg Sch Publ Hlth, Dept Mental Hlth, Baltimore, MD USA. EM vikram.patel@lshtm.ac.uk RI Minas, Harry/F-7718-2010; OI Minas, Harry/0000-0003-1719-7367; Chen-Edinboro, Lenis/0000-0002-8927-4256; Bass, Judith/0000-0002-5192-628X FU NIMH NIH HHS [T32 MH014592]; Wellcome Trust [091834] NR 22 TC 18 Z9 18 U1 0 U2 6 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1549-1277 J9 PLOS MED JI PLos Med. PD JAN PY 2012 VL 9 IS 1 AR e1001159 DI 10.1371/journal.pmed.1001159 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 894IE UT WOS:000300419600007 PM 22272191 ER PT J AU Ciaranello, AL Perez, F Keatinge, J Park, JE Engelsmann, B Maruva, M Walensky, RP Dabis, F Chu, J Rusibamayila, A Mushavi, A Freedberg, KA AF Ciaranello, Andrea L. Perez, Freddy Keatinge, Jo Park, Ji-Eun Engelsmann, Barbara Maruva, Matthews Walensky, Rochelle P. Dabis, Francois Chu, Jennifer Rusibamayila, Asinath Mushavi, Angela Freedberg, Kenneth A. TI What Will It Take to Eliminate Pediatric HIV? Reaching WHO Target Rates of Mother-to-Child HIV Transmission in Zimbabwe: A Model-Based Analysis SO PLOS MEDICINE LA English DT Article ID SINGLE-DOSE NEVIRAPINE; SUB-SAHARAN AFRICA; ANTIRETROVIRAL THERAPY PROGRAMS; RESOURCE-LIMITED SETTINGS; PLACEBO-CONTROLLED TRIAL; SAMPLING-BASED APPROACH; LOWER-INCOME COUNTRIES; DAR-ES-SALAAM; FOLLOW-UP; RANDOMIZED-TRIAL AB Background: The World Health Organization (WHO) has called for the "virtual elimination'' of pediatric HIV: a mother-to-child HIV transmission (MTCT) risk of less than 5%. We investigated uptake of prevention of MTCT (PMTCT) services, infant feeding recommendations, and specific drug regimens necessary to achieve this goal in Zimbabwe. Methods and Findings: We used a computer model to simulate a cohort of HIV-infected, pregnant/breastfeeding women (mean age, 24 y; mean CD4, 451/mu l; breastfeeding duration, 12 mo). Three PMTCT regimens were evaluated: (1) single-dose nevirapine (sdNVP), (2) WHO 2010 guidelines' "Option A'' (zidovudine in pregnancy, infant nevirapine throughout breastfeeding for women without advanced disease, lifelong combination antiretroviral therapy for women with advanced disease), and (3) WHO "Option B'' (pregnancy/breastfeeding-limited combination antiretroviral drug regimens without advanced disease; lifelong antiretroviral therapy with advanced disease). We examined four levels of PMTCT uptake (proportion of pregnant women accessing and adhering to PMTCT services): reported rates in 2008 and 2009 (36% and 56%, respectively) and target goals in 2008 and 2009 (80% and 95%, respectively). The primary model outcome was MTCT risk at weaning. The 2008 sdNVP-based National PMTCT Program led to a projected 12-mo MTCT risk of 20.3%. Improved uptake in 2009 reduced projected risk to 18.0%. If sdNVP were replaced by more effective regimens, with 2009 (56%) uptake, estimated MTCT risk would be 14.4% (Option A) or 13.4% (Option B). Even with 95% uptake of Option A or B, projected transmission risks (6.1%-7.7%) would exceed the WHO goal of less than 5%. Only if the lowest published transmission risks were used for each drug regimen, or breastfeeding duration were shortened, would MTCT risks at 95% uptake fall below 5%. Conclusions: Implementation of the WHO PMTCT guidelines must be accompanied by efforts to improve access to PMTCT services, retain women in care, and support medication adherence throughout pregnancy and breastfeeding, to approach the "virtual elimination'' of pediatric HIV in Zimbabwe. C1 [Ciaranello, Andrea L.; Walensky, Rochelle P.; Freedberg, Kenneth A.] Massachusetts Gen Hosp, Med Practice Evaluat Ctr, Div Infect Dis, Boston, MA 02114 USA. [Perez, Freddy; Dabis, Francois] Univ Bordeaux Segalen, Inst Sante Publ Epidemiol & Dev, Africa Team, INSERM,U897, Bordeaux, France. [Perez, Freddy] Pan Amer Hlth Org, HIV AIDS Unit, Washington, DE USA. [Keatinge, Jo; Maruva, Matthews] Elizabeth Glaser Pediat AIDS Fdn, Zimbabwe Country Off, Harare, Zimbabwe. [Park, Ji-Eun; Chu, Jennifer; Rusibamayila, Asinath; Freedberg, Kenneth A.] Massachusetts Gen Hosp, Med Practice Evaluat Ctr, Div Gen Med, Boston, MA 02114 USA. [Engelsmann, Barbara] Org Publ Hlth Intervent & Dev, Harare, Zimbabwe. [Walensky, Rochelle P.] Brigham & Womens Hosp, Div Infect Dis, Boston, MA 02115 USA. [Mushavi, Angela] Minist Hlth & Child Welf, Harare, Zimbabwe. [Freedberg, Kenneth A.] Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA 02115 USA. [Walensky, Rochelle P.; Freedberg, Kenneth A.] Harvard Univ, Ctr AIDS Res, Boston, MA 02115 USA. RP Ciaranello, AL (reprint author), Massachusetts Gen Hosp, Med Practice Evaluat Ctr, Div Infect Dis, Boston, MA 02114 USA. EM aciaranello@partners.org OI Walensky, Rochelle P./0000-0002-8795-379X FU Elizabeth Glaser Pediatric AIDS Foundation; National Institute of Allergy and Infectious Disease [K01 AI078754, K24 AI062476, R01 AI058736] FX Funding for this work was provided by the Elizabeth Glaser Pediatric AIDS Foundation (all authors) and the National Institute of Allergy and Infectious Disease (K01 AI078754 [ALC], K24 AI062476 [KAF], R01 AI058736 [KAF, RPW, JC, JP]). The funders had no role in study design, interpretation of results, or decision to publish. NR 97 TC 32 Z9 32 U1 2 U2 11 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1549-1277 J9 PLOS MED JI PLos Med. PD JAN PY 2012 VL 9 IS 1 AR e1001156 DI 10.1371/journal.pmed.1001156 PG 15 WC Medicine, General & Internal SC General & Internal Medicine GA 894IE UT WOS:000300419600004 PM 22253579 ER PT J AU Fava, M Mischoulon, D Iosifescu, D Witte, J Pencina, M Flynn, M Harper, L Levy, M Rickels, K Pollack, M AF Fava, Maurizio Mischoulon, David Iosifescu, Dan Witte, Janet Pencina, Michael Flynn, Martina Harper, Linda Levy, Michael Rickels, Karl Pollack, Mark TI A Double-Blind, Placebo-Controlled Study of Aripiprazole Adjunctive to Antidepressant Therapy among Depressed Outpatients with Inadequate Response to Prior Antidepressant Therapy (ADAPT-A Study) SO PSYCHOTHERAPY AND PSYCHOSOMATICS LA English DT Article DE Antidepressant; Augmentation therapy; Major depressive disorder; Placebo ID REPORT QIDS-SR; PSYCHOMETRIC EVALUATION; QUICK INVENTORY; CLINICAL-TRIALS; DISORDER; QUESTIONNAIRE; AUGMENTATION; SYMPTOMATOLOGY; MULTICENTER; EFFICACY AB Background: We assessed the efficacy of low-dose aripiprazole added to antidepressant therapy (ADT) in major depressive disorder (MDD) patients with inadequate response to prior ADT. Methods: As per the sequential parallel comparison design, 225 MDD subjects were randomized to adjunctive treatment with aripiprazole 2 mg/day or placebo across two 30-day phases, with a 2:3:3 randomization ratio to drug/drug (aripiprazole 2 mg/day in phase 1; 5 mg/day in phase 2), placebo/placebo (placebo in both phases), and placebo/drug (placebo in phase 1; aripiprazole 2 mg/day in phase 2). Eligible subjects were patients whose MDD was independently deemed 'valid' with SAFER criteria. Subjects had been receiving ADT for >= 8 weeks, and had inadequate response to >= 1 and <4 adequate ADTs in the current episode, as defined by the Antidepressant Treatment Response Questionnaire. Results: The pooled, weighted response difference between aripiprazole 2 mg/day and placebo in the two phases was 5.6% (p = 0.18; NS). The aripiprazole 2 mg/day-placebo difference on the Montgomery-Asberg Depression Rating Scale pooled across the two phases was -1.51 (p = 0.065; NS). Other secondary endpoint analyses showed non-significant pooled differences favoring aripiprazole over placebo. Of the 225 randomized subjects in phase 1, 2 dropped out in both arms, while in phase 2, of 138 phase 1 placebo nonresponders, 9 dropped out on aripiprazole and 5 on placebo. There were only minimal differences in adverse event rates between treatments, except for constipation, weight gain, and dry mouth, more common on aripiprazole. Conclusions: This study provides clear support for the tolerability of low-dose aripiprazole as an ADT-augmenting agent, with marginal efficacy. Copyright (C) 2012 S. Karger AG, Basel C1 [Fava, Maurizio] Massachusetts Gen Hosp, Dept Psychiat, CTNI, Boston, MA 02114 USA. [Pencina, Michael] Boston Univ, Dept Biostat, Boston, MA 02215 USA. [Harper, Linda] CNS Healthcare, Orlando, FL USA. [Iosifescu, Dan] Mt Sinai Sch Med, Mood & Anxiety Disorders Program, New York, NY USA. [Levy, Michael] Staten Isl, Behav Med Res, New York, NY USA. [Rickels, Karl] Univ Penn, Sch Med, Dept Psychiat, Philadelphia, PA 19104 USA. [Pollack, Mark] Rush Med Coll, Dept Psychiat, Chicago, IL 60612 USA. RP Fava, M (reprint author), Massachusetts Gen Hosp, Dept Psychiat, CTNI, 55 Fruit St,Bulfinch 351, Boston, MA 02114 USA. EM MFava@partners.org FU Bristol-Myers Squibb FX This was an investigator-initiated study supported by Bristol-Myers Squibb, which also provided blinded study medication. NR 25 TC 50 Z9 50 U1 1 U2 10 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0033-3190 J9 PSYCHOTHER PSYCHOSOM JI Psychother. Psychosom. PY 2012 VL 81 IS 2 BP 87 EP 97 DI 10.1159/000332050 PG 11 WC Psychiatry; Psychology SC Psychiatry; Psychology GA 894JE UT WOS:000300422200004 PM 22286203 ER PT J AU Xiao, ZY Levy-Nissenbaum, E Alexis, F Luptak, A Teply, BA Chan, JM Shi, JJ Digga, E Cheng, J Langer, R Farokhzad, OC AF Xiao, Zeyu Levy-Nissenbaum, Etgar Alexis, Frank Luptak, Andrej Teply, Benjamin A. Chan, Juliana M. Shi, Jinjun Digga, Elise Cheng, Judy Langer, Robert Farokhzad, Omid C. TI Engineering of Targeted Nanoparticles for Cancer Therapy Using Internalizing Aptamers Isolated by Cell-Uptake Selection SO ACS NANO LA English DT Article DE nanoparticles; internalization; in vitro selection; aptamer; targeted cancer therapy ID MEMBRANE ANTIGEN PSMA; PROSTATE-CANCER; DRUG-DELIVERY; EXPONENTIAL ENRICHMENT; SYSTEMATIC EVOLUTION; IN-VITRO; ANTIBODY; EFFICACY; LIGANDS; HETEROGENEITY AB One of the major challenges in the development of targeted nanoparticles (NPs) for cancer therapy Is to discover targeting ligands that allow for differential binding and uptake by the target cancer cells. Using prostate cancer (PCa) as a model disease, we developed a cell-uptake selection strategy to isolate PCa-specific internalizing 2'-O-methyl RNA aptamers (Apts) for NP incorporation. Twelve cycles of selection and counter-selection were done to obtain a panel of internalizing Apts, which can distinguish PCa cells from nonprostate and normal prostate cells. After Apt characterization, size minimization, and conjugation of the Apts with fluorescently labeled polymeric NPs, the NP Apt conjugates exhibit PCa specificity and enhancement In cellular uptake when compared to nontargeted NPs lacking the Internalizing Apts. Furthermore, when docetaxel, a chemotherapeutic agent used for the treatment of PCa, was encapsulated within the NP Apt, a significant improvement In cytotoxicity was achieved in targeted PCa cells. Rather than Isolating high-affinity Apts as reported in previous selection processes, our selection strategy was designed to enrich cancer cell-specific internalizing Apts. A similar cell-uptake selection strategy may be used to develop specific internalizing ligands for a myriad of other diseases and can potentially facilitate delivering various molecules, including chugs and siRNAs, into target cells. C1 [Xiao, Zeyu; Levy-Nissenbaum, Etgar; Alexis, Frank; Teply, Benjamin A.; Shi, Jinjun; Digga, Elise; Cheng, Judy; Farokhzad, Omid C.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Lab Nanomed & Biomat,Dept Anesthesiol, Boston, MA 02115 USA. [Xiao, Zeyu; Levy-Nissenbaum, Etgar; Alexis, Frank; Teply, Benjamin A.; Shi, Jinjun; Cheng, Judy; Langer, Robert; Farokhzad, Omid C.] MIT, MIT Harvard Ctr Canc Nanotechnol Excellence, Cambridge, MA 02139 USA. [Chan, Juliana M.; Langer, Robert] MIT, David H Koch Inst Integrat Canc Res, Cambridge, MA 02139 USA. [Luptak, Andrej] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. [Luptak, Andrej] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Boston, MA 02114 USA. [Chan, Juliana M.] MIT, Dept Biol, Cambridge, MA 02139 USA. RP Farokhzad, OC (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Lab Nanomed & Biomat,Dept Anesthesiol, Boston, MA 02115 USA. EM ofarokhzad@zeus.bwh.harvard.edu RI Chan, Juliana/E-8646-2014; Dong, Ping/H-4011-2016 OI Chan, Juliana/0000-0002-7489-3716; FU National Institutes of Health [CA151884, EB003647]; David Koch Prostate Cancer Foundation; USA Department of Defence [PC 051156] FX E.L-N. dedicates this work in memory of Emilia Levy. We thank Jack W. Szostak, Brian Haines, and Noam Shomron for helpful discussions and suggestions. We thank Rosa Larraide-Ridaura for helping with the sequence identification. This research was supported by National Institutes of Health Grants CA151884 and EB003647, the David Koch Prostate Cancer Foundation Award in Nanotherapeutics, and the USA Department of Defence Prostate Cancer Research Program PC 051156. R.L. and O.C.F. disclose their financial interest in BIND Biosciences and Selecta Biosciences, two biotechnology companies developing nanoparticle technologies for medical applications. NR 41 TC 86 Z9 90 U1 11 U2 87 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1936-0851 J9 ACS NANO JI ACS Nano PD JAN PY 2012 VL 6 IS 1 BP 696 EP 704 DI 10.1021/nn204165v PG 9 WC Chemistry, Multidisciplinary; Chemistry, Physical; Nanoscience & Nanotechnology; Materials Science, Multidisciplinary SC Chemistry; Science & Technology - Other Topics; Materials Science GA 879YH UT WOS:000299368300084 PM 22214176 ER PT J AU Sohani, AR Sohani, MA AF Sohani, Aliyah R. Sohani, Moez A. TI Static digital telepathology: A model for diagnostic and educational support to pathologists in the developing world SO ANALYTICAL CELLULAR PATHOLOGY LA English DT Article DE Telepathology; static imaging; developing world; teledermatopathology; telecytology ID TELEMEDICINE PLATFORM; IPATH AB Background: The practice of pathology in the developing world presents challenges in terms of limited resources, shortages of trained personnel, and lack of continuing education programs. Telepathology holds promise as a means of diagnostic and educational support. Methods: We donated multiheaded teaching microscopes equipped with digital cameras to four hospitals in Eastern Africa and trained local pathologists on their use. Static images of challenging cases were posted on a web-based telepathology platform. A U. S.-based pathologist reviewed images in consultation with subspecialist colleagues. Results: Over a period of 40 months, 109 cases were submitted for second opinion consultation, including 29 dermatopathology cases (26.6%), 14 hematopathology cases (12.8%), and 13 cases each (11.9%) in cytopathology and bone and soft tissue pathology. Static images enabled a complete or partial diagnosis in 100/109 cases (91.7%). Factors precluding a definitive diagnosis included absence of confirmatory immunophenotyping, technical issues, or lack of clinical history. Case responses included a diagnosis and discussion, including differential diagnosis, references, and treatment recommendations. Conclusion: Static digital telepathology is a simple, cost-effective, reliable and efficient means to provide diagnostic and educational support to pathologists in the developing world. Additional training may help overcome technical factors precluding a definitive diagnosis in certain cases. C1 [Sohani, Aliyah R.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Sohani, Aliyah R.] Harvard Univ, Sch Med, Boston, MA USA. [Sohani, Moez A.] Tufts Univ, Fletcher Sch Law & Diplomacy, Medford, MA 02155 USA. RP Sohani, AR (reprint author), Massachusetts Gen Hosp, Dept Pathol, 55 Fruit St,WRN 219, Boston, MA 02114 USA. EM arsohani@partners.org FU Aga Khan Health Board, USA; Aga Khan Foundation, USA; Department of Pathology, Massachusetts General Hospital (MGH) FX The authors wish to thank the Aga Khan Health Board, USA, the Aga Khan Foundation, USA, and the Department of Pathology, Massachusetts General Hospital (MGH) for their support of the telepathology program; Telemed Basel and the AKDN eHealth Resource Centre for their support of the internet-based platforms that were used during this study; and all of the pathologists at MGH and other institutions who have generously donated their time and expertise in evaluating these cases. NR 13 TC 8 Z9 8 U1 0 U2 0 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 2210-7177 J9 ANAL CELL PATHOL JI Anal. Cell. Pathol. PY 2012 VL 35 IS 1 BP 25 EP 30 DI 10.3233/ACP-2011-0032 PG 6 WC Oncology; Cell Biology; Pathology SC Oncology; Cell Biology; Pathology GA 889VF UT WOS:000300102100005 PM 22233701 ER PT J AU Bautista, PA Yagi, Y AF Bautista, Pinky A. Yagi, Yukako TI Multispectral enhancement towards digital staining SO ANALYTICAL CELLULAR PATHOLOGY LA English DT Article DE Multispectral imaging; multispectral enhancement; spectral enhancement; digital staining; digital pathology ID DISPLAY; IMAGES AB Background: Digital staining can be considered as a special form of image enhancement wherein the concern is not only to increase the contrast between the background objects and objects of interest, but to also impart the colors that mark the objects' unique reactions to a specific stain. In this paper, we extended the previously proposed multispectral enhancement methods such that the colors of the background pixels can also be changed. Methods: In the previous multispectral enhancement methods a shifting factor is provided to the original spectrum. To implement digital staining, a spectral transformation process is introduced prior to spectral shifting. Results: The enhancement method is applied to multispectral images of H&E stained liver tissue. The resulting digitally stained images show good correlation with the serial-section images of the tissue which were physically stained with Masson's trichrome. Conclusions: We have presented a multispectral enhancement method that can be adjusted to produce digitally stained-images. The current experimental results show the viability of the method. However, to achieve robust enhancement performance issues that arise from variations in staining conditions has to be addressed as well. This would be part of our future work. C1 [Bautista, Pinky A.; Yagi, Yukako] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA 02114 USA. RP Bautista, PA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA 02114 USA. EM pbautista@partners.org NR 8 TC 2 Z9 2 U1 0 U2 1 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 2210-7177 J9 ANAL CELL PATHOL JI Anal. Cell. Pathol. PY 2012 VL 35 IS 1 BP 51 EP 55 DI 10.3233/ACP-2011-0038 PG 5 WC Oncology; Cell Biology; Pathology SC Oncology; Cell Biology; Pathology GA 889VF UT WOS:000300102100009 PM 22002722 ER PT J AU McClintock, DS Lee, RE Gilbertson, JR AF McClintock, David S. Lee, Roy E. Gilbertson, John R. TI Using computerized workflow simulations to assess the feasibility of whole slide imaging full adoption in a high-volume histology laboratory SO ANALYTICAL CELLULAR PATHOLOGY LA English DT Article DE Whole slide imaging; virtual microscopy; workflow; histology; business analysis software; computer simulations; process modeling; BPMN ID PATIENT FLOW; IMPLEMENTATION AB Background: Whole slide Imaging (WSI) has been touted by many as the future of pathology, with estimates of full adoption occurring sometime in the next 5 to 15 years. While WSI devices have become increasingly capable since their inception, there has been little consideration of how WSI will be implemented and subsequently affect the workflow of high-volume histology laboratories. Methods: Histology workflow process data was collected from a high-volume histology laboratory (Massachusetts General Hospital) and a process model developed using business process management software. Computerized workflow simulations were performed and total histology process time evaluated under a number of different WSI conditions. Results: Total histology process time increased approximately 10-fold to 20-fold over baseline with the presence of one WSI robot in the histology workflow. Depending on the specifications of the WSI robot, anywhere from 9 to 14 WSI robots were required within the histology workflow to minimize the effects of WSI. Conclusions: Placing a WSI robot into the current workflow of a high-volume histology laboratory with the intent of full adoption is not feasible. Implementing WSI without making significant changes to the current workflow of the histology laboratory would prove to be both disruptive and costly to surgical pathology. C1 [McClintock, David S.; Lee, Roy E.; Gilbertson, John R.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP McClintock, DS (reprint author), Massachusetts Gen Hosp, Dept Pathol, Warren Bldg 225, Boston, MA 02114 USA. EM dsmcclin@gmail.com NR 11 TC 3 Z9 3 U1 0 U2 2 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 2210-7177 J9 ANAL CELL PATHOL JI Anal. Cell. Pathol. PY 2012 VL 35 IS 1 BP 57 EP 64 DI 10.3233/ACP-2011-0034 PG 8 WC Oncology; Cell Biology; Pathology SC Oncology; Cell Biology; Pathology GA 889VF UT WOS:000300102100010 PM 21987587 ER PT J AU Yagi, Y Yoshioka, S Kyusojin, H Onozato, M Mizutani, Y Osato, K Yada, H Mark, EJ Frosch, MP Louis, DN AF Yagi, Yukako Yoshioka, Shigeatsu Kyusojin, Hiroshi Onozato, Maristela Mizutani, Yoichi Osato, Kiyoshi Yada, Hiroaki Mark, Eugene J. Frosch, Matthew P. Louis, David N. TI An ultra-high speed whole slide image viewing system SO ANALYTICAL CELLULAR PATHOLOGY LA English DT Article DE Ultra-high speed viewing system; whole slide imaging; PS3 (R) AB Background: One of the goals for a Whole Slide Imaging (WSI) system is implementation in the clinical practice of pathology. One of the unresolved problems in accomplishing this goal is the speed of the entire process, i.e., from viewing the slides through making the final diagnosis. Most users are not satisfied with the correct viewing speeds of available systems. We have evaluated a new WSI viewing station and tool that focuses on speed. Method: A prototype WSI viewer based on PlayStation (R) 3 with wireless controllers was evaluated at the Department of Pathology at MGH for the following reasons: 1. For the simulation of signing-out cases; 2. Enabling discussion at a consensus conference; and 3. Use at slide seminars during a Continuing Medical Education course. Results: Pathologists were being able to use the system comfortably after 0-15 min training. There were no complaints regarding speed. Most pathologists were satisfied with the functionality, usability and speed of the system. The most difficult situation was simulating diagnostic sign-out. Conclusions: The preliminary results of adapting the Sony PlayStation (R) 3 (PS3 (R)) as an ultra-high speed WSI viewing system were promising. The achieved speed is consistent with what would be needed to use WSI in daily practice. C1 [Yagi, Yukako] Massachusetts Gen Hosp, MGH Pathol Imaging & Commun Technol PICT Ctr, Pathol Serv, Boston, MA 02114 USA. [Yagi, Yukako; Onozato, Maristela; Mark, Eugene J.; Frosch, Matthew P.; Louis, David N.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Yoshioka, Shigeatsu; Kyusojin, Hiroshi; Mizutani, Yoichi; Osato, Kiyoshi; Yada, Hiroaki] Sony Corp, Tokyo, Japan. RP Yagi, Y (reprint author), Massachusetts Gen Hosp, MGH Pathol Imaging & Commun Technol PICT Ctr, Pathol Serv, 101 Merrimac St,Suite 820, Boston, MA 02114 USA. EM yyagi@partners.org NR 4 TC 2 Z9 2 U1 0 U2 2 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 2210-7177 J9 ANAL CELL PATHOL JI Anal. Cell. Pathol. PY 2012 VL 35 IS 1 BP 65 EP 73 DI 10.3233/ACP-2011-0042 PG 9 WC Oncology; Cell Biology; Pathology SC Oncology; Cell Biology; Pathology GA 889VF UT WOS:000300102100011 PM 22063731 ER PT J AU Onozato, ML Klepeis, VE Yagi, Y Mino-Kenudson, M AF Onozato, Maristela L. Klepeis, Veronica E. Yagi, Yukako Mino-Kenudson, Mari TI A role of three-dimensional (3D)-reconstruction in the classification of lung adenocarcinoma SO ANALYTICAL CELLULAR PATHOLOGY LA English DT Article DE Lung; adenocarcinoma; solid; micropapillary; classification; histology; 3D; automation ID SERIAL SECTIONS; EXPRESSION AB Background: Three-dimensional (3D)-reconstruction from paraffin embedded sections has been considered laborious and time-consuming. However, the high-resolution images of large object areas and different fields of view obtained by 3D-reconstruction make one wonder whether it can add a new insight into lung adenocarcinoma, the most frequent histology type of lung cancer characterized by its morphological heterogeneity. Objective: In this work, we tested whether an automated tissue sectioning machine and slide scanning system could generate precise 3D-reconstruction of microanatomy of the lung and help us better understand and define histologic subtypes of lung adenocarcinoma. Methods: Four formalin-fixed human lung adenocarcinoma resections were studied. Paraffin embedded tissues were sectioned with Kurabo Automated tissue sectioning machine and serial sections were automatically stained and scanned with a whole slide imaging system. The resulting stacks of images were 3D reconstructed by Pannoramic Viewer software. Results: Two of the four specimens contained islands of tumor cells detached in alveolar spaces that had not been described in any of the existing adenocarcinoma classifications. 3D-reconstruction revealed the details of spatial distribution and structural interaction of the tumor that could hardly be observed by 2D light microscopy studies. The islands of tumor cells extended into a deeper aspect of the tissue, and were interconnected with each other and with the main tumor with a solid pattern that was surrounded by the islands. The finding raises the question whether the islands of tumor cells should be classified into a solid pattern in the current classification. Conclusion: The combination of newtechnologies enabled us to build an effective 3D-reconstruction of resected lung adenocarcinomas. 3D-reconstruction may help us refine the classification of lung adenocarcinoma by adding detailed spatial/structural information to 2D light microscopy evaluation. C1 [Onozato, Maristela L.; Klepeis, Veronica E.; Yagi, Yukako; Mino-Kenudson, Mari] Harvard Univ, Dept Pathol, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. RP Onozato, ML (reprint author), Harvard Univ, Dept Pathol, Massachusetts Gen Hosp, Sch Med, 101 Merrimac St,Suite 820, Boston, MA 02114 USA. EM likaono@gmail.com NR 8 TC 12 Z9 12 U1 0 U2 2 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 2210-7177 J9 ANAL CELL PATHOL JI Anal. Cell. Pathol. PY 2012 VL 35 IS 2 BP 79 EP 84 DI 10.3233/ACP-2011-0030 PG 6 WC Oncology; Cell Biology; Pathology SC Oncology; Cell Biology; Pathology GA 889VI UT WOS:000300102500002 PM 21955723 ER PT J AU Ayad, E Yagi, Y AF Ayad, Essam Yagi, Yukako TI Virtual microscopy beyond the pyramids, applications of WSI in Cairo University for E-education & telepathology SO ANALYTICAL CELLULAR PATHOLOGY LA English DT Article DE Telepathology; Egypt; Cairo University; Italy; UCDMC; WSI; E-learning AB Background: Telepathology, the practice of pathology at a long distance, has advanced continuously since 1986. The progress of telepathology passed through four stages: Static, Dynamic, Hybrid & Whole Slide Imaging. Materials and methods: A pilot project between the Italian Hospital in Cairo& the Civico Hospital in Palermo was completed successfully, applying the static & dynamic techniques of telepathology. This project began in 2003 and continued till now. In 2004, centers in Venice, London and Pittsburgh participated actively in our project. Results: Over eight years we consulted on many problematic pathological cases with specialized pathological centers in Italy, UK & USA. In addition to the highly specialized scientific value, we saved a lot of time and money. Conclusion: We concluded from our experience that telepathology is a very useful and applicable tool for additional consulting on difficult pathological cases especially for emerging countries. In view of this success we have already established our Digital Telepathology Unit in Cairo University, using the WSI technique in teaching which was greatly successful and encouraged us to build a huge digital pathology library which will expand our telepathology & E-learning programs to cover staff and students in Egypt and Eastern Mediterranean. C1 [Ayad, Essam] Cairo Univ, Dept Pathol, Fac Med, Digital Pathol Unit, Cairo, Egypt. [Yagi, Yukako] Massachusetts Gen Hosp, MGH Pathol Imaging & Commun Technol PICT Ctr, Boston, MA 02114 USA. RP Ayad, E (reprint author), Cairo Univ, Dept Pathol, Fac Med, Digital Pathol Unit, Cairo, Egypt. EM essamayad@yahoo.com NR 5 TC 7 Z9 7 U1 1 U2 8 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 2210-7177 J9 ANAL CELL PATHOL JI Anal. Cell. Pathol. PY 2012 VL 35 IS 2 BP 93 EP 95 DI 10.3233/ACP-2011-0027 PG 3 WC Oncology; Cell Biology; Pathology SC Oncology; Cell Biology; Pathology GA 889VI UT WOS:000300102500004 PM 22297472 ER PT J AU Malon, C Brachtel, E Cosatto, E Graf, HP Kurata, A Kuroda, M Meyer, JS Saito, A Wu, SL Yagi, Y AF Malon, Christopher Brachtel, Elena Cosatto, Eric Graf, Hans Peter Kurata, Atsushi Kuroda, Masahiko Meyer, John S. Saito, Akira Wu, Shulin Yagi, Yukako TI Mitotic figure recognition: Agreement among pathologists and computerized detector SO ANALYTICAL CELLULAR PATHOLOGY LA English DT Article ID BREAST-CANCER; REPRODUCIBILITY; PROLIFERATION; INDEX; GRADE AB Despite the prognostic importance of mitotic count as one of the components of the Bloom - Richardson grade [3], several studies [2, 9, 10] have found that pathologists' agreement on the mitotic grade is fairly modest. Collecting a set of more than 4,200 candidate mitotic figures, we evaluate pathologists' agreement on individual figures, and train a computerized system for mitosis detection, comparing its performance to the classifications of three pathologists. The system's and the pathologists' classifications are based on evaluation of digital micrographs of hematoxylin and eosin stained breast tissue. On figures where the majority of pathologists agree on a classification, we compare the performance of the trained system to that of the individual pathologists. We find that the level of agreement of the pathologists ranges from slight to moderate, with strong biases, and that the system performs competitively in rating the ground truth set. This study is a step towards automatic mitosis count to accelerate a pathologist's work and improve reproducibility. C1 [Malon, Christopher; Cosatto, Eric; Graf, Hans Peter] NEC Labs Amer, Dept Machine Learning, Princeton, NJ 08540 USA. [Brachtel, Elena; Wu, Shulin; Yagi, Yukako] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Brachtel, Elena; Wu, Shulin; Yagi, Yukako] Harvard Univ, Sch Med, Boston, MA USA. [Kurata, Atsushi; Kuroda, Masahiko] Tokyo Med Univ, Dept Mol Pathol, Tokyo, Japan. [Meyer, John S.] St Lukes Hosp St Louis, Dept Pathol, Chesterfield, MO USA. [Saito, Akira] NEC Corp Ltd, Innovat Serv Solut Div, Tokyo, Japan. RP Malon, C (reprint author), NEC Labs Amer, Dept Machine Learning, 4 Independence Way, Princeton, NJ 08540 USA. EM malon@nec-labs.com NR 13 TC 8 Z9 8 U1 0 U2 6 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 2210-7177 J9 ANAL CELL PATHOL JI Anal. Cell. Pathol. PY 2012 VL 35 IS 2 BP 97 EP 100 DI 10.3233/ACP-2011-0029 PG 4 WC Oncology; Cell Biology; Pathology SC Oncology; Cell Biology; Pathology GA 889VI UT WOS:000300102500005 PM 21965283 ER PT J AU Sharma, A Bautista, P Yagi, Y AF Sharma, Anurag Bautista, Pinky Yagi, Yukako TI Balancing image quality and compression factor for special stains whole slide images SO ANALYTICAL CELLULAR PATHOLOGY LA English DT Article DE Special stains; image; quality factor; compression; whole slide; image quality; digital pathology AB The objective is to find a practical balance between quality and performance for daily high volume whole slide imaging. We evaluated whole slide images created by various scanners at different compression factors to determine the best suitable quality factor (QF) needed for pathological images of special stains. Method: We scanned two sets of eight special stains slides each at 0.50 mu m/pixel resolution in Hamamatsu scanner at six and five QF levels respectively to generate 72 images which were observed at a calibrated monitor by imaging specialists, a histo-technician, and a pathologist to find the most suitable QF level for special stains in digital slides. Results: Most special stains images were acceptable at QF 30 except for the stain Reticulin where the lowest acceptable QF was 50. The compression of images from QF 90 to QF 50 reduced the size of the images by 62.73%. Conclusion: 0.50 mu m/pixel images at QF 50 or above were found suitable 12 special stain. C1 [Sharma, Anurag; Bautista, Pinky; Yagi, Yukako] Harvard Univ, Dept Pathol, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. [Sharma, Anurag] NEC Labs Amer Inc, Princeton, NJ USA. RP Sharma, A (reprint author), Harvard Univ, Dept Pathol, Massachusetts Gen Hosp, Sch Med, 101 Merrimac St,Ste 820, Boston, MA 02114 USA. EM asharma@nec-labs.com NR 3 TC 3 Z9 3 U1 0 U2 0 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 2210-7177 J9 ANAL CELL PATHOL JI Anal. Cell. Pathol. PY 2012 VL 35 IS 2 BP 101 EP 106 DI 10.3233/ACP-2011-0035 PG 6 WC Oncology; Cell Biology; Pathology SC Oncology; Cell Biology; Pathology GA 889VI UT WOS:000300102500006 PM 21987586 ER PT J AU Weintraub, D Dietz, N Duda, JE Wolk, DA Doshi, J Xie, SX Davatzikos, C Clark, CM Siderowf, A AF Weintraub, Daniel Dietz, Nicole Duda, John E. Wolk, David A. Doshi, Jimit Xie, Sharon X. Davatzikos, Christos Clark, Christopher M. Siderowf, Andrew TI Alzheimer's disease pattern of brain atrophy predicts cognitive decline in Parkinson's disease SO BRAIN LA English DT Article DE Alzheimer's disease; dementia; mild cognitive impairment; Parkinson's disease; neurodegeneration ID DEMENTIA RATING-SCALE; LEWY BODIES; ELASTIC REGISTRATION; MCI PATIENTS; BASE-LINE; IMPAIRMENT; HALLUCINATIONS; HIPPOCAMPAL; BETA; CLASSIFICATION AB Research suggests overlap in brain regions undergoing neurodegeneration in Parkinson's and Alzheimer's disease. To assess the clinical significance of this, we applied a validated Alzheimer's disease-spatial pattern of brain atrophy to patients with Parkinson's disease with a range of cognitive abilities to determine its association with cognitive performance and decline. At baseline, 84 subjects received structural magnetic resonance imaging brain scans and completed the Dementia Rating Scale-2, and new robust and expanded Dementia Rating Scale-2 norms were applied to cognitively classify participants. Fifty-nine non-demented subjects were assessed annually with the Dementia Rating Scale-2 for two additional years. Magnetic resonance imaging scans were quantified using both a region of interest approach and voxel-based morphometry analysis, and a method for quantifying the presence of an Alzheimer's disease spatial pattern of brain atrophy was applied to each scan. In multivariate models, higher Alzheimer's disease pattern of atrophy score was associated with worse global cognitive performance (beta = -0.31, P = 0.007), including in non-demented patients (beta = -0.28, P = 0.05). In linear mixed model analyses, higher baseline Alzheimer's disease pattern of atrophy score predicted long-term global cognitive decline in non-demented patients [F(1, 110) = 9.72, P = 0.002], remarkably even in those with normal cognition at baseline [F(1, 80) = 4.71, P = 0.03]. In contrast, in cross-sectional and longitudinal analyses there was no association between region of interest brain volumes and cognitive performance in patients with Parkinson's disease with normal cognition. These findings support involvement of the hippocampus and parietal-temporal cortex with cognitive impairment and long-term decline in Parkinson's disease. In addition, an Alzheimer's disease pattern of brain atrophy may be a preclinical biomarker of cognitive decline in Parkinson's disease. C1 [Weintraub, Daniel] Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA. [Weintraub, Daniel; Duda, John E.] Philadelphia Vet Affairs Med Ctr, Parkinsons Dis Res Educ & Clin Ctr PADRECC, Philadelphia, PA USA. [Weintraub, Daniel] Philadelphia Vet Affairs Med Ctr, Mental Illness Res Educ & Clin Ctr MIRECC, Philadelphia, PA USA. [Weintraub, Daniel; Dietz, Nicole; Duda, John E.; Wolk, David A.; Clark, Christopher M.; Siderowf, Andrew] Univ Penn, Dept Neurol, Philadelphia, PA 19104 USA. [Doshi, Jimit; Davatzikos, Christos] Univ Penn, Dept Radiol, Philadelphia, PA 19104 USA. [Xie, Sharon X.] Univ Penn, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA. [Clark, Christopher M.] Avid Radiopharmaceut, Philadelphia, PA 19104 USA. RP Weintraub, D (reprint author), Univ Penn, Dept Psychiat, 3615 Chestnut St,330, Philadelphia, PA 19104 USA. EM daniel.weintraub@uphs.upenn.edu FU Department of Health of the Commonwealth of Pennsylvania [SAP4100027296, 2001-77]; National Institute of Neurological Disorders and Strokes [NS-053488]; National Institute of Aging [R01-14971, P30-AG10124] FX This work was supported by a health research grant [grant number SAP4100027296] awarded by the Department of Health of the Commonwealth of Pennsylvania from the Tobacco Master Settlement Agreement under Act 2001-77, the National Institute of Neurological Disorders and Strokes [NS-053488], and the National Institute of Aging [R01-14971 and P30-AG10124]. NR 77 TC 54 Z9 56 U1 1 U2 8 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0006-8950 J9 BRAIN JI Brain PD JAN PY 2012 VL 135 BP 170 EP 180 DI 10.1093/brain/awr277 PN 1 PG 11 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 888ZX UT WOS:000300044400024 PM 22108576 ER PT J AU Biederman, J Mick, E Spencer, T Surman, C Faraone, SV AF Biederman, Joseph Mick, Eric Spencer, Thomas Surman, Craig Faraone, Stephen V. TI Is Response to OROS-Methylphenidate Treatment Moderated by Treatment with Antidepressants or Psychiatric Comorbidity? A Secondary Analysis from a Large Randomized Double Blind Study of Adults with ADHD SO CNS NEUROSCIENCE & THERAPEUTICS LA English DT Article DE ADHD; Adult; Comorbidity; Methylphenidate; Moderators; Pharmacotherapy ID ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; DEFICIT HYPERACTIVITY DISORDER; PLACEBO-CONTROLLED TRIAL; SUBSTANCE USE; SURVEY REPLICATION; EFFICACY; METAANALYSIS; DEPRESSION; ASSOCIATION; PREVALENCE AB Aims: The main aim of this post hoc analysis was to evaluate whether response to osmotic release oral system (OROS) methylphenidate (OROS-MPH) was moderated by the concomitant use of antidepressants in attention-deficit/hyperactivity disorder (ADHD) adults stabilized on these medicines for the treatment of depression or anxiety disorders, or a history of mood, anxiety, or substance use disorders. Methods: Two hundred and ninety-six subjects were screened for participation; 227 were randomized (112 to OROS-MPH and 115 to placebo), and 223 were analyzed (N= 109 and N= 114 for OROS-MPH and placebo, respectively). Subjects with anxiety disorders and depression treated with a stable medication regimen of non-MAOI antidepressants or benzodiazepines for at least 3 months could be enrolled in the study. Subjects currently receiving pharmacotherapy for anxiety disorders or depression were required to have Hamilton-Depression and Hamilton-Anxiety rating scales below 15 (mild range). Results: Concomitant antidepressant use at baseline was not associated with ADHD response, OROS-MPH dose, study completion rate, adverse effects, or exacerbation of anxiety/depression. We did find nominally significant evidence that a lifetime history of mood (P= 0.09) or anxiety (P= 0.04) disorders was a moderator of ADHD symptoms and that a lifetime history of substance use disorder (P= 0.02) was a potential moderator of dose at endpoint. Discussion and Conclusions: We found few moderating effects in this large clinical trial of OROS-MPH in adults with ADHD, which supports the robustness of the clinical response to OROS-MPH in adult ADHD despite variable clinical pictures. C1 [Biederman, Joseph; Mick, Eric; Spencer, Thomas; Surman, Craig] Massachusetts Gen Hosp, Clin & Res Program Pediat Psychopharmacol & Adult, Boston, MA 02114 USA. [Biederman, Joseph; Mick, Eric; Spencer, Thomas; Surman, Craig] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Faraone, Stephen V.] SUNY Upstate Med Univ, Dept Psychiat, Syracuse, NY USA. [Faraone, Stephen V.] SUNY Upstate Med Univ, Dept Neurosci & Physiol, Syracuse, NY USA. RP Biederman, J (reprint author), Massachusetts Gen Hosp, Clin & Res Program Pediat Psychopharmacol & Adult, 55 Fruit St,Warren 705, Boston, MA 02114 USA. EM jbiederman@partners.org OI Mick, Eric/0000-0001-8505-8145; Faraone, Stephen/0000-0002-9217-3982 FU Ortho-McNeil Janssen Scientific Affairs, LLC.; Pediatric Psychopharmacology Council; Elminda; Janssen; McNeil; Next Wave Pharmaceuticals; Shire; MGH Psychiatry Academy; Eli Lilly; AstraZeneca; Fundacion Dr. Manuel Camelo A. C. in Monterrey Mexico; Fundacion Areces (Spain); Medice Pharmaceuticals (Germany); Spanish Child Psychiatry Association; Abbott; Alza; Boston University; Bristol Myers Squibb; Celltech; Cephalon; Eli Lilly and Co.; Esai; Forest; Glaxo; Gliatech; Hastings Center; Merck; MMC Pediatric; NARSAD; NIDA; New River; NICHD; NIMH; Novartis; Noven; Neurosearch; Organon; Otsuka; Pfizer; Pharmacia; Phase V Communications; Physicians Academy; Prechter Foundation; Quantia Communications; Reed Exhibitions; Stanley Foundation; UCB Pharma Inc.; Veritas; Wyeth; Ortho-McNeil Janssen Scientific Affairs; Shire Pharmaceuticals; Shire Laboratories Inc; Glaxo-Smith Kline; McNeil Pharmaceutical; Movartis Pharmaceuticals; ElMinda the Hilda and Preston Davis Foundation; National Institutes of Health; Takeda FX Clinical trials were supported with financial support from Ortho-McNeil Janssen Scientific Affairs, LLC. Secondary analyses were conducted with the support of the Pediatric Psychopharmacology Council Fund.; Dr. Joseph Biederman is currently receiving research support from the following sources: Elminda, Janssen, McNeil, Next Wave Pharmaceuticals, and Shire. In 2011, he gave a single unpaid talk for Juste Pharmaceutical Spain, and received honoraria from the MGH Psychiatry Academy for a tuition-funded CME course. He also received an honorarium from Cambridge University Press for a chapter publication. Dr. Biederman received departmental royalties from a copyrighted rating scale used for ADHD diagnoses, paid by Eli Lilly, Shire, and AstraZeneca; these royalties are paid to the Department of Psychiatry at MGH. In 2010, he received a speaker's fee from a single talk given at Fundacion Dr. Manuel Camelo A. C. in Monterrey Mexico. Dr. Biederman provided single consultations for Shionogi Pharma Inc. and Cipher Pharmaceuticals Inc.; the honoraria for these consultations were paid to the Department of Psychiatry at the MGH. He received honoraria from the MGH Psychiatry Academy for a tuition-funded CME course. In 2009, he received a speaker's fee from the following sources: Fundacion Areces (Spain), Medice Pharmaceuticals (Germany) and the Spanish Child Psychiatry Association. In previous years, Dr. Joseph Biederman received research support, consultation fees, or speaker's fees for/from the following additional sources: Abbott, Alza, AstraZeneca, Boston University, Bristol Myers Squibb, Celltech, Cephalon, Eli Lilly and Co., Esai, Forest, Glaxo, Gliatech, Hastings Center, Janssen, McNeil, Merck, MMC Pediatric, NARSAD, NIDA, New River, NICHD, NIMH, Novartis, Noven, Neurosearch, Organon, Otsuka, Pfizer, Pharmacia, Phase V Communications, Physicians Academy, The Prechter Foundation, Quantia Communications, Reed Exhibitions, Shire, The Stanley Foundation, UCB Pharma Inc., Veritas, and Wyeth. Dr. Eric Mick, research supports: Ortho-McNeil Janssen Scientific Affairs, Pfizer, Shire Pharmaceuticals, and has been an advisory board member for Shire Pharmaceuticals; Dr. Thomas Spencer has received research support from the following sources: Shire Laboratories Inc, Cephalon, Eli Lilly & Company, Glaxo-Smith Kline, Janssen, McNeil Pharmaceutical, Movartis Pharmaceuticals, Pfizer, NIMH. He has been a speaker or on a speaker's bureau for the following pharmaceutical companies: Shire Laboratories Inc, Eli Lilly & Company, Glaxo-Smith Kline, Janssen, McNeil Pharmaceutical, Novartis Pharmaceuticals. He has been an advisor or on an advisory board for the following pharmaceutical companies: Shire Laboratories Inc, Cephalon, Eli Lilly & Company, Glaxo-Smith Kline, Janssen, McNeil Pharmaceutical, Novartis Pharmaceuticals, and Pfizer. He receives research support from Royalties and Licensing fees on copyrighted ADHD scales through MGH Corporate Sponsored Research and Licensing. He also has a US Patent Application pending (Provisional Number 61/233,686), through MGH Corporate Licensing, on a method to prevent stimulant abuse. Dr. Craig Surman, research supports: Abbott, Alza, Cephalon, Eli Lilly, ElMinda the Hilda and Preston Davis Foundation, McNeil, Merck, New River, National Institutes of Health, Organon, Pfizer, Shire, and Takeda; Dr. Stephen Faraone, research supports: Eli Lilly, Pfizer, Shire and the National Institutes of Health. NR 34 TC 6 Z9 7 U1 0 U2 5 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1755-5930 J9 CNS NEUROSCI THER JI CNS Neurosci. Ther. PY 2012 VL 18 IS 2 BP 126 EP 132 DI 10.1111/j.1755-5949.2010.00233.x PG 7 WC Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA 888KF UT WOS:000300001700005 PM 22070421 ER PT J AU Deckersbach, T Holzel, BK Eisner, LR Stange, JP Peckham, AD Dougherty, DD Rauch, SL Lazar, S Nierenberg, AA AF Deckersbach, Thilo Hoelzel, Britta K. Eisner, Lori R. Stange, Jonathan P. Peckham, Andrew D. Dougherty, Darin D. Rauch, Scott L. Lazar, Sara Nierenberg, Andrew A. TI Mindfulness-Based Cognitive Therapy for Nonremitted Patients with Bipolar Disorder SO CNS NEUROSCIENCE & THERAPEUTICS LA English DT Article DE Bipolar disorder; Cognitive-behavior therapy; Mindfulness-based cognitive therapy; Residual symptoms; Well-being ID RANDOMIZED CONTROLLED-TRIAL; INTERNATIONAL NEUROPSYCHIATRIC INTERVIEW; TREATMENT ENHANCEMENT PROGRAM; GENERALIZED ANXIETY DISORDER; BEHAVIORAL-APPROACH SYSTEM; FAMILY-FOCUSED TREATMENT; SOCIAL RHYTHM THERAPY; LIFE EVENTS; SPECTRUM DISORDERS; I-DISORDER AB Introduction: Bipolar disorder is characterized by recurrent episodes of depression and/or mania along with interepisodic mood symptoms that interfere with psychosocial functioning. Despite periods of symptomatic recovery, many individuals with bipolar disorder continue to experience substantial residual mood symptoms that often lead to the recurrence of mood episodes. Aims: This study explored whether a new mindfulness-based cognitive therapy (MBCT) for bipolar disorder would increase mindfulness, reduce residual mood symptoms, and increase emotion-regulation abilities, psychological well-being, positive affect, and psychosocial functioning. Following a baseline clinical assessment, 12 individuals with DSM-IV bipolar disorder were treated with 12 group sessions of MBCT. Results: At the end of treatment, as well as at the 3 months follow-up, participants showed increased mindfulness, lower residual depressive mood symptoms, less attentional difficulties, and increased emotion-regulation abilities, psychological well-being, positive affect, and psychosocial functioning. Conclusions: These findings suggest that treating residual mood symptoms with MBCT may be another avenue to improving mood, emotion regulation, well-being, and functioning in individuals with bipolar disorder. C1 [Deckersbach, Thilo] Massachusetts Gen Hosp, Bipolar Clin & Res Program, Dept Psychiat, Boston, MA 02114 USA. [Deckersbach, Thilo; Hoelzel, Britta K.; Eisner, Lori R.; Dougherty, Darin D.; Rauch, Scott L.; Lazar, Sara; Nierenberg, Andrew A.] Harvard Univ, Sch Med, Boston, MA USA. [Hoelzel, Britta K.] Univ Giessen, Giessen, Germany. [Rauch, Scott L.] McLean Hosp, Dept Psychiat, Belmont, MA 02178 USA. RP Deckersbach, T (reprint author), Massachusetts Gen Hosp, Bipolar Clin & Res Program, Dept Psychiat, 50 Staniford St,5th Floor, Boston, MA 02114 USA. EM tdeckersbach@partners.org RI Lazar, Sara/G-3809-2012 OI Lazar, Sara/0000-0003-1126-8363 FU K-23 NIMH [1K23MH074895] FX This work was supported by a K-23 NIMH Career Award 1K23MH074895 to Thilo Deckersbach. Part of this research has been presented at the annual meeting of the World Congress for Cognitive and Behavior Therapies, Boston, 2010. NR 81 TC 43 Z9 43 U1 6 U2 56 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1755-5930 J9 CNS NEUROSCI THER JI CNS Neurosci. Ther. PY 2012 VL 18 IS 2 BP 133 EP 141 DI 10.1111/j.1755-5949.2011.00236.x PG 9 WC Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA 888KF UT WOS:000300001700006 PM 22070469 ER PT J AU Nguyen, CA Akiba, Y Kaunitz, JD AF Nguyen, C. A. Akiba, Y. Kaunitz, J. D. TI Recent Advances in Gut Nutrient Chemosensing SO CURRENT MEDICINAL CHEMISTRY LA English DT Review DE Fatty acids; amino acids; bile acids; G Protein-coupled receptors; enteroendocrine cells; gut hormones; cholecystokinin; glucagon-like peptide; metabotropic glutamate receptor; TIR2/TIR3; SGLT1; transgenic mice; obesity; diabetes ID PROTEIN-COUPLED RECEPTOR; GLUCAGON-LIKE PEPTIDE-1; GASTRIC-ACID-SECRETION; FREE FATTY-ACIDS; EXTRACELLULAR CA2+-SENSING RECEPTOR; SODIUM-GLUCOSE COTRANSPORTER; CALCIUM-SENSING RECEPTOR; CANDIDATE TASTE RECEPTOR; RAT DUODENAL MUCOSA; CELL-LINE STC-1 AB The field of gut nutrient chemosensing is evolving rapidly. Recent advances have uncovered the mechanism by which specific nutrient components evoke multiple metabolic responses. Deorphanization of G protein-coupled receptors (GPCRs) in the gut has helped identify previously unliganded receptors and their cognate ligands. In this review, we discuss nutrient receptors, their ligand preferences, and the evoked neurohormonal responses. Family A GPCRs includes receptor GPR93, which senses protein and proteolytic degradation products, and free fatty acid-sensing receptors. Short-chain free fatty acids are ligands for FFA2, previously GPR43, and FFA3, previously GPR41. FFA1, previously GPR40, is activated by long-chain fatty acids with GPR120 activated by medium-and long-chain fatty acids. The GPR119 agonist ethanolamide oleoylethanolamide (OEA) and bile acid GPR131 agonists have also been identified. Family C receptors ligand preferences include L-amino acids, carbohydrate, and tastants. The metabotropic glutamate receptor (mGluR), calcium-sensing receptor (CaR), and GPCR family C, group 6, subtype A receptor (GPRC6A) mediate L-amino acid-sensing. Taste receptors have a proposed role in intestinal chemosensing; sweet, bitter, and umami evoke responses in the gut via GPCRs. The mechanism of carbohydrate-sensing remains controversial: the heterodimeric taste receptor T1R2/T1R3 and sodium glucose cotransporter 1 (SGLT-1) expressed in L cells are the two leading candidates. Identification of specific nutrient receptors and their respective ligands can provide novel therapeutic targets for the treatment of diabetes, acid reflux, foregut mucosal injury, and obesity. C1 [Kaunitz, J. D.] W Los Angeles VAMC, Dept Med, Los Angeles, CA 90073 USA. [Nguyen, C. A.] W Los Angeles Vet Affairs Med Ctr, Dept Nutr, Los Angeles, CA 90073 USA. [Akiba, Y.] W Los Angeles Vet Affairs Med Ctr, Dept Res, Los Angeles, CA 90073 USA. [Akiba, Y.; Kaunitz, J. D.] Univ Calif Los Angeles, Sch Med, Dept Med, Los Angeles, CA 90073 USA. [Akiba, Y.; Kaunitz, J. D.] CURE DDRC Digest Dis Ctr, Los Angeles, CA 90073 USA. RP Kaunitz, JD (reprint author), W Los Angeles VAMC, Dept Med, 11301 Wilshire Blvd,Bldg 114,Suite 217E, Los Angeles, CA 90073 USA. EM jake@ucla.edu FU NIDDK NIH HHS [R01 DK054221] NR 90 TC 20 Z9 20 U1 3 U2 32 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 0929-8673 J9 CURR MED CHEM JI Curr. Med. Chem. PD JAN PY 2012 VL 19 IS 1 BP 28 EP 34 PG 7 WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy GA 890XH UT WOS:000300179300005 PM 22300073 ER PT J AU Tache, Y AF Tache, Y. TI Brainstem Neuropeptides and Vagal Protection of the Gastric Mucosal Against Injury: Role of Prostaglandins, Nitric Oxide and Calcitonin-Gene Related Peptide in Capsaicin Afferents SO CURRENT MEDICINAL CHEMISTRY LA English DT Review DE Adrenomedullin; CGRP; ethanol; ghrelin; nitric oxide; prostaglandins; TRH; vagus ID THYROTROPIN-RELEASING-HORMONE; CENTRAL-NERVOUS-SYSTEM; DORSAL MOTOR NUCLEUS; URETHANE-ANESTHETIZED RATS; PYY-PREFERRING RECEPTORS; ACID-SECRETION; TRH ANALOG; INTRACISTERNAL TRH; ADAPTIVE CYTOPROTECTION; MESSENGER-RNA AB Earlier experimental studies indicated that the integrity of vagal pathway was required to confer gastric protection against damaging agents. Several peptides located in the brainstem initially identified to influence vagal outflow to the stomach, as assessed by electrophysiological approach or by vagal dependent alterations of gastric secretory and motor function, were investigated for their influence in the vagal regulation of the resistance of the gastric mucosa to injury. Thyrotropin releasing hormone (TRH), or its stable TRH analog, RX-77368, injected at low doses into the cisterna magna or the dorsal motor nucleus (DMN) was the first peptide reported to protect the gastric mucosa against ethanol injury through stimulation of vagal cholinergic pathways, inducing the release of gastric prostaglandins/nitric oxide (NO) and the recruitment of efferent function of capsaicin sensitive afferent fibers containing calcitonin-gene related peptide (CGRP). Activation of endogenous TRH-TRH1 receptor signaling located in the brainstem plays a role in adaptive gastric protection against damaging agents. Since then, an expanding number of peptides, namely peptide YY, CGRP, adrenomedullin, amylin, glugacon-like peptide, opioid peptides acting on, 1 or 2 receptors, nocicpetin, nocistatin, ghrelin, leptin and TLQP-21, a peptide derived from VGF prohormone, have been reported to act in the brainstem to afford gastric protection against ethanol injury largely through similar peripheral effectors mechanisms than TRH. Therefore gastric prostaglandins and CGRP/NO pathways represent a common final mechanism through which brain peptides confer vagally mediated gastroprotection against injury. A better understanding of brain circuitries through which these peptides are released will provide new strategies to recruit integrated and multifaceted gastroprotective mechanisms. C1 [Tache, Y.] Univ Calif Los Angeles, CURE Digest Dis Res Ctr, VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. [Tache, Y.] Univ Calif Los Angeles, David Geffen Sch Med, Ctr Neurovisceral Sci & Womens Hlth, Div Digest Dis, Los Angeles, CA 90073 USA. RP Tache, Y (reprint author), Univ Calif Los Angeles, CURE Digest Dis Res Ctr, VA Greater Los Angeles Healthcare Syst, Bldg 115,Room 117,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM ytache@mednet.ucla.edu FU Veteran Affairs Research Career Scientist Award; National Institute of Health [DK-33061, DK-57238, DK-41301] FX Yvette Tache is in receipt of Veteran Affairs Research Career Scientist Award and Merit Award and National Institute of Health grants R01grants, DK-33061 and DK-57238, and Center grant DK-41301 (Animal core). We thank Ms. Eugenia Hu for helping in the preparation of the manuscript. No potential conflict of interest. NR 129 TC 27 Z9 30 U1 0 U2 4 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y-2, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 0929-8673 J9 CURR MED CHEM JI Curr. Med. Chem. PD JAN PY 2012 VL 19 IS 1 BP 35 EP 42 PG 8 WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy GA 890XH UT WOS:000300179300006 PM 22300074 ER PT J AU Madrigano, J Baccarelli, A Mittleman, MA Sparrow, D Vokonas, PS Tarantini, L Schwartz, J AF Madrigano, Jaime Baccarelli, Andrea Mittleman, Murray A. Sparrow, David Vokonas, Pantel S. Tarantini, Letizia Schwartz, Joel TI Aging and epigenetics Longitudinal changes in gene-specific DNA methylation SO EPIGENETICS LA English DT Article DE aging; DNA methylation; epigenesis; genetic ID PROMOTER METHYLATION; HUMAN COLON; AGE; ATHEROSCLEROSIS; NEOPLASIA; CANCER AB DNA methylation has been associated with age-related disease. Intra-individual changes in gene-specific DNA methylation over time in a community-based cohort has not been well described. We estimated the change in DNA methylation due to aging for nine genes in an elderly, community-dwelling cohort of men. Seven hundred and eighty four men from the Veterans Administration Normative Aging Study who were living in metropolitan Boston from 19992009 donated a blood sample for DNA methylation analysis at clinical examinations repeated at approximately 3-5 year intervals. We used mixed effects regression models. Aging was significantly associated with decreased methylation of GCR, iNOS and TLR2 and with increased methylation of IFN gamma, F3, CRAT and OGG. Obstructive pulmonary disease at baseline modified the effect of aging on methylation of IFN gamma (interaction p = 0.04). For participants who had obstructive pulmonary disease at their baseline visit, the rate of change of methylation of IFN gamma was -0.05% 5-methyl-cytosine (5-mC) per year (95% CI: -0.22, 0.13), but was 0.14% 5-mC per year (95% CI: 0.05, 0.24) for those without this condition. Models with random slopes indicated significant heterogeneity in the effect of aging on methylation of GCR, iNOS and OGG. These findings suggest that DNA methylation may reflect differential biological aging. C1 [Madrigano, Jaime] Columbia Univ, Earth Inst, New York, NY 10027 USA. [Madrigano, Jaime] Columbia Univ, Mailman Sch Publ Hlth, New York, NY USA. [Madrigano, Jaime; Baccarelli, Andrea; Schwartz, Joel] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. [Mittleman, Murray A.; Schwartz, Joel] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Mittleman, Murray A.] Beth Israel Deaconess Med Ctr, Cardiovasc Epidemiol Res Unit, Boston, MA 02215 USA. [Sparrow, David; Vokonas, Pantel S.] Boston Univ, Sch Med, VA Boston Healthcare Syst, VA Normat Aging Study, Boston, MA 02118 USA. [Sparrow, David; Vokonas, Pantel S.] Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA. [Sparrow, David] Harvard Univ, Brigham & Womens Hosp, Sch Med, Channing Lab, Boston, MA 02115 USA. [Tarantini, Letizia] Univ Milan, Ctr Mol & Genet Epidemiol, IRCCS Ca Granda Maggiore Policlin Hosp Fdn, Milan, Italy. [Tarantini, Letizia] Univ Milan, Dept Environm & Occupat Hlth, Milan, Italy. RP Madrigano, J (reprint author), Columbia Univ, Earth Inst, New York, NY 10027 USA. EM jm3731@columbia.edu OI Baccarelli, Andrea/0000-0002-3436-0640 FU National Institue of Environmental Health Sciences at the National Institutes of Health [T32ES07069, ES0002, ES015172-01, ES014663, T32ES016645]; Epidemiology Research and Information Center of the US. Department of Veterans Affairs FX This work was supported by the National Institue of Environmental Health Sciences at the National Institutes of Health (T32ES07069, ES0002, ES015172-01, ES014663 and T32ES016645). The VA NAS is supported by the Cooperative Studies Program/Epidemiology Research and Information Center of the US. Department of Veterans Affairs and is a component of the Massachusetts Veterans Epidemiology Research and Information Center, Boston, MA. NR 36 TC 42 Z9 46 U1 5 U2 13 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 1559-2294 J9 EPIGENETICS-US JI Epigenetics PD JAN PY 2012 VL 7 IS 1 BP 63 EP 70 DI 10.4161/epi.7.1.18749 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 886CN UT WOS:000299828900008 PM 22207354 ER PT J AU Geoerger, B Kieran, MW Grupp, S Perek, D Clancy, J Krygowski, M Ananthakrishnan, R Boni, JP Berkenblit, A Spunt, SL AF Geoerger, Birgit Kieran, Mark W. Grupp, Stephan Perek, Danuta Clancy, Jill Krygowski, Mizue Ananthakrishnan, Revathi Boni, Joseph P. Berkenblit, Anna Spunt, Sheri L. TI Phase II trial of temsirolimus in children with high-grade glioma, neuroblastoma and rhabdomyosarcoma SO EUROPEAN JOURNAL OF CANCER LA English DT Article DE Temsirolimus; mTOR; Child; Adolescent; Glioma; Neuroblastoma; Rhabdomyosarcoma; Clinical trial; Phase II ID CHILDHOOD-CANCER SURVIVOR; RENAL-CELL CARCINOMA; MAMMALIAN TARGET; SOLID TUMORS; MTOR INHIBITION; CCI-779; THERAPY; PATHWAY; GROWTH; MALIGNANCIES AB Purpose: A phase II study of temsirolimus was conducted in children and adolescents with high-grade glioma, neuroblastoma or rhabdomyosarcoma. Patients and methods: Temsirolimus 75 mg/m(2) was administered once weekly until disease progression or intolerance. Using the Simon 2-stage design, further enrolment in each disease cohort required >= 2 objective responses within the first 12 weeks for the first 12 evaluable patients (those who received >= 3 temsirolimus doses). Results: Fifty-two heavily pretreated patients with relapsed (12%) or refractory (88%) disease, median age 8 years (range 1-21 years), were enroled and treated. One patient with neuroblastoma achieved confirmed partial response within the first 12 weeks; thus, none of the 3 cohorts met the criterion for continued enrolment. Disease stabilisation at week 12 was observed in 7 of 17 patients (41%) with high-grade glioma (5 diffuse pontine gliomas, 1 glioblastoma multiforme and 1 anaplastic astrocytoma), 6 of 19 (32%) with neuroblastoma and 1 of 16 (6%) with rhabdomyosarcoma (partial response confirmed at week 18). In the three cohorts, median duration of stable disease or better was 128, 663 and 75 d, respectively. The most common treatment-related adverse events were thrombocytopaenia, hyperlipidaemia and aesthenia. Pharmacokinetic findings were similar to those observed in adults. Conclusions: Temsirolimus administered weekly at the dose of 75 mg/m(2) did not meet the primary objective efficacy threshold in children with high-grade glioma, neuroblastoma or rhabdomyosarcoma; however, meaningful prolonged stable disease merits further evaluation in combination therapy. (C) 2011 Elsevier Ltd. All rights reserved. C1 [Geoerger, Birgit] Univ Paris 11, Inst Gustave Roussy, Dept Paediat & Adolescent Med, F-94805 Villejuif, France. [Kieran, Mark W.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Kieran, Mark W.] Childrens Hosp, Boston, MA 02115 USA. [Grupp, Stephan] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. [Perek, Danuta] Childrens Mem Hlth Inst, Warsaw, Poland. [Clancy, Jill; Ananthakrishnan, Revathi] inVentiv Clin Solut, Cambridge, MA USA. [Krygowski, Mizue] Pfizer Oncol Res, Cambridge, MA USA. [Boni, Joseph P.; Berkenblit, Anna] Pfizer Oncol Res, Collegeville, PA USA. [Spunt, Sheri L.] St Jude Childrens Hosp, Memphis, TN 38105 USA. [Spunt, Sheri L.] Univ Tennessee, Ctr Hlth Sci, Memphis, TN 38163 USA. RP Geoerger, B (reprint author), Univ Paris 11, Inst Gustave Roussy, Dept Paediat & Adolescent Med, 114 Rue Edouard Vaillant, F-94805 Villejuif, France. EM geoerger@igr.fr OI Kieran, Mark/0000-0003-2184-7692 FU Wyeth Research; Pfizer Inc.; Wyeth FX This study was sponsored by Wyeth Research, which was acquired by Pfizer Inc. in October 2009. A. Berkenblit provided data acquisition and manuscript preparation and review. J. Boni provided study concepts and design (pharmacokinetics), data analysis and interpretation, and manuscript review. M. Krygowski provided statistical analysis, quality control analysis and interpretation of data, and manuscript preparation and review. R. Ananthakrishnan provided statistical analysis, quality control, analysis and interpretation of data and manuscript preparation, editing and review. J Clancy provided analysis and interpretation of data and manuscript preparation, editing, and review. Christine H. Blood, PhD, of Peloton Advantage provided assistance with manuscript preparation, which was funded by Pfizer Inc.; No author received an honorarium or other forms of financial support related to the development of this manuscript. D. Perek, and S. Spunt received research funding from Wyeth for the conduct of this study. B. Geoerger, M.W. Kieran and S. Grupp disclose no potential conflicts of interest. J. Clancy is an employee of inVentiv Clinical Solutions, a paid consultant to Pfizer Inc. Mizue Krygowski is an employee of Wyeth Pharmaceuticals/Pfizer Inc. R. Ananthakrishnan is an employee of inVentiv Clinical Solutions, a paid consultant to Pfizer Inc. J.P. Boni and A. Berkenblit are employees of and stockholders in Wyeth Pharmaceuticals/Pfizer Inc. No other potential conflicts of interest were disclosed. NR 42 TC 46 Z9 47 U1 0 U2 5 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0959-8049 J9 EUR J CANCER JI Eur. J. Cancer PD JAN PY 2012 VL 48 IS 2 BP 253 EP 262 DI 10.1016/j.ejca.2011.09.021 PG 10 WC Oncology SC Oncology GA 891EK UT WOS:000300199800013 PM 22033322 ER PT J AU Park, D Sykes, DB Scadden, DT AF Park, Dongsu Sykes, David B. Scadden, David T. TI The hematopoietic stem cell niche SO FRONTIERS IN BIOSCIENCE-LANDMARK LA English DT Article DE Hematopoietic Stem Cells; Niche; Osteoblasts; Endothelial Cells; Review ID COLONY-STIMULATING FACTOR; ACUTE MYELOID-LEUKEMIA; BONE-MARROW NICHE; CXCR4 ANTAGONIST AMD3100; PROGENITOR CELLS; IN-VIVO; SELF-RENEWAL; ENDOTHELIAL-CELLS; MOUSE MODEL; N-CADHERIN AB Hematopoietic stem cells (HSCs) possess the ability to self-renew and to differentiate to mature progeny along multiple different hematopoietic lineages. The function of HSCs depends upon the signals from surrounding cells found within the highly specialized microenvironment termed the hematopoietic stem cell niche. Understanding and exploiting the HSC niche is a goal of basic scientists and clinicians alike. Recent studies have focused on defining the cellular components and molecular factors critical to this microenvironment. Here we review recent findings, discuss unresolved questions, and examine the clinical implications of our current knowledge of the HSC niche. C1 [Park, Dongsu; Sykes, David B.; Scadden, David T.] Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA 02114 USA. [Park, Dongsu; Sykes, David B.; Scadden, David T.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Park, Dongsu; Sykes, David B.; Scadden, David T.] Harvard Stem Cell Inst, Cambridge, MA 02138 USA. [Park, Dongsu; Sykes, David B.; Scadden, David T.] Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA. RP Scadden, DT (reprint author), 185 Cambridge St, Boston, MA 02115 USA. EM dscadden@mgh.harvard.edu FU Leukemia & Lymphoma Society; American Society of Hematology; National Institutes of Health FX This work was supported by a Leukemia & Lymphoma Society Fellowship award (D.P), American Society of Hematology Fellowship award (D.B.S), and grants of the National Institutes of Health (D.T.S.) NR 58 TC 23 Z9 24 U1 1 U2 7 PU FRONTIERS IN BIOSCIENCE INC PI IRVINE PA 16471 SCIENTIFIC WAY, IRVINE, CA 92618 USA SN 1093-9946 J9 FRONT BIOSCI-LANDMRK JI Front. Biosci. PD JAN 1 PY 2012 VL 17 BP 30 EP 39 DI 10.2741/3913 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 889BG UT WOS:000300047900003 PM 22201730 ER PT J AU Brusic, A Wu, CJ AF Brusic, Ana Wu, Catherine J. TI Enhancing graft-versus-leukemia after transplant: the rise of anti-cancer vaccines SO FRONTIERS IN BIOSCIENCE-LANDMARK LA English DT Article DE HSCT; Cancer Vaccine; Antigen Discovery; Whole Cell; Defined Antigen; GM-CSF; Negative Immune Regulation; TLR agonists; CD40L; CTLA-4; PD-1; Review ID STEM-CELL TRANSPLANTATION; BONE-MARROW-TRANSPLANTATION; CHRONIC MYELOGENOUS LEUKEMIA; DONOR LYMPHOCYTE INFUSION; COLONY-STIMULATING FACTOR; CHRONIC MYELOID-LEUKEMIA; REGULATORY T-CELLS; PULSED DENDRITIC CELLS; MINOR HISTOCOMPATIBILITY ANTIGENS; MULTIPLE-MYELOMA AB Allogeneic hematopoietic stem cell transplantation (HSCT) remains the only truly effective curative treatment for refractory hematological malignancies. Unfortunately, relapse and transplant rejection continue to be of major concern. In order to enhance the effectiveness of the HSCT, various strategies have been explored to amplify the graft versus leukemia (GvL) effect. Cancer vaccines have emerged in recent years as a promising strategy for the immunotherapeutic treatment of cancer. Evidence shows that they are most likely to have the greatest effect in the setting of minimal residual disease and as adjuvant agents. With this in mind, researchers have begun to explore the use of cancer vaccines in conjunction with HSCT, with exciting results. There has also been recent work examining the effect of novel adjuvants or blockers of negative immune regulation to augment the effect of cancer vaccines in both the transplant and non-transplant settings. The addition of these agents may prove vital to developing effective vaccine based strategies. C1 [Brusic, Ana; Wu, Catherine J.] Harvard Inst Med, Dana Farber Canc Inst, Canc Vaccine Ctr, Boston, MA 02115 USA. [Brusic, Ana] Monash Univ, Melbourne, Vic 3004, Australia. [Wu, Catherine J.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Wu, Catherine J.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med, Boston, MA 02115 USA. RP Wu, CJ (reprint author), Harvard Inst Med, Dana Farber Canc Inst, Canc Vaccine Ctr, Rm 416B,77 Ave Louis Pasteur, Boston, MA 02115 USA. EM cwu@partners.org FU NCI [5R21CA115043-2]; Blavatnik Family Foundation; Leukemia and Lymphoma Translational Research Program; Howard Hughes Medical Institute; Damon-Runyon Cancer Research Foundation [CI-38-07] FX None of the authors have conflicts of interest to disclose. C.J.W. acknowledges support from the NCI (5R21CA115043-2), the Blavatnik Family Foundation, the Leukemia and Lymphoma Translational Research Program, the Early Career Physician-Scientist Award of the Howard Hughes Medical Institute, and is a Damon-Runyon Clinical Investigator supported in part by the Damon-Runyon Cancer Research Foundation (CI-38-07). NR 144 TC 4 Z9 4 U1 0 U2 3 PU FRONTIERS IN BIOSCIENCE INC PI IRVINE PA 16471 SCIENTIFIC WAY, IRVINE, CA 92618 USA SN 1093-9946 J9 FRONT BIOSCI-LANDMRK JI Front. Biosci. PD JAN 1 PY 2012 VL 17 BP 635 EP 655 DI 10.2741/3949 PG 21 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 889BX UT WOS:000300049600016 PM 22201766 ER PT J AU Arbelaez, C Wright, EA Losina, E Millen, JC Kimmel, S Dooley, M Reichmann, WM Mikulinsky, R Walensky, RP AF Arbelaez, Christian Wright, Elizabeth A. Losina, Elena Millen, Jennifer C. Kimmel, Simeon Dooley, Matthew Reichmann, William M. Mikulinsky, Regina Walensky, Rochelle P. TI EMERGENCY PROVIDER ATTITUDES AND BARRIERS TO UNIVERSAL HIV TESTING IN THE EMERGENCY DEPARTMENT SO JOURNAL OF EMERGENCY MEDICINE LA English DT Article DE HIV/AIDS; testing; emergency department; emergency providers ID INTIMATE PARTNER VIOLENCE; FOR-DISEASE-CONTROL; PREVENTION GUIDELINES; INFECTION; HEALTH; OUTCOMES; NURSES; ADULTS; TRIAGE AB Background: The Centers for Disease Control and Prevention (CDC) recently published recommendations for routine, voluntary human immunodeficiency virus (HIV) testing of adults in all health care settings, including the emergency department (ED). Study Objective: The objective of this study was to examine the willingness of ED providers to offer HIV testing, as well as their perceived barriers to implementation of these guidelines. Methods: Before the establishment of a routine HIV testing program in the ED, a 21-item survey was used to assess ED providers' knowledge, attitudes, and perceived challenges to HIV testing. Six months after program initiation, the identical survey was re-administered to determine whether HIV testing program experience altered providers' perceptions. Results: There were 108 of 146 (74%) providers who completed both the pre- and post-implementation surveys. Although the majority of emergency providers at 6 months were supportive of an ED-based HIV testing program (59/108 [55%]), only 38% (41/108) were willing to offer the HIV test most or all of the time. At 6 months, the most frequently cited barriers to offering a test were: inadequate time (67/108 [62%]), inadequate resources (65/108 [60%]), and concerns regarding provision of follow-up care (64/108 [59%]). Conclusions: After the implementation of a large-scale HIV testing program in an ED, the majority of emergency providers were supportive of routine HIV testing. Nevertheless, 6 months after program initiation, providers were still reluctant to offer the test due to persistent barriers. Further studies are needed to identify feasible implementation strategies that minimize barriers to routine HIV testing in the ED. (C) 2012 Elsevier Inc. C1 [Arbelaez, Christian; Millen, Jennifer C.; Kimmel, Simeon; Dooley, Matthew] Brigham & Womens Hosp, Dept Emergency Med, Boston, MA 02115 USA. [Wright, Elizabeth A.; Losina, Elena; Reichmann, William M.; Mikulinsky, Regina] Brigham & Womens Hosp, Dept Orthoped Surg, Boston, MA 02115 USA. [Reichmann, William M.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. [Walensky, Rochelle P.] Brigham & Womens Hosp, Dept Med, Div Infect Dis, Boston, MA 02115 USA. [Walensky, Rochelle P.] Massachusetts Gen Hosp, Dept Med, Div Infect Dis, Boston, MA 02114 USA. [Walensky, Rochelle P.] Massachusetts Gen Hosp, Dept Med, Div Gen Med, Boston, MA 02114 USA. [Walensky, Rochelle P.] Harvard Univ, Sch Med, Ctr AIDS Res, Boston, MA USA. RP Arbelaez, C (reprint author), Brigham & Womens Hosp, Dept Emergency Med, 75 Francis St, Boston, MA 02115 USA. OI Walensky, Rochelle P./0000-0002-8795-379X FU National Institute of Mental Health [R01 MH0735445, R01 MH65869]; Doris Duke Charitable Foundation [NCT00502944] FX This research was funded by the National Institute of Mental Health (R01 MH0735445, R01 MH65869) and the Doris Duke Charitable Foundation (Clinical Scientist Development Award to Rochelle P. Walensky, MD, MPH), ClinicalTrials.Gov: #NCT00502944. NR 24 TC 24 Z9 24 U1 1 U2 7 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0736-4679 J9 J EMERG MED JI J. Emerg. Med. PD JAN PY 2012 VL 42 IS 1 BP 7 EP 14 DI 10.1016/j.jemermed.2009.07.038 PG 8 WC Emergency Medicine SC Emergency Medicine GA 890KB UT WOS:000300142400002 PM 19828278 ER PT J AU Capp, R Chang, YC Brown, DFM AF Capp, Roberta Chang, Yuchiao Brown, David F. M. TI ACCURACY OF MICROSCOPIC URINE ANALYSIS AND CHEST RADIOGRAPHY IN PATIENTS WITH SEVERE SEPSIS AND SEPTIC SHOCK SO JOURNAL OF EMERGENCY MEDICINE LA English DT Article DE chest radiography; microscopic urine analysis; pneumonia; urinary tract infection ID ANTIMICROBIAL THERAPY; TRACT-INFECTIONS; EPIDEMIOLOGY; PNEUMONIA; INITIATION; SURVIVAL; OUTCOMES AB Background: Diagnosis of source of infection in patients with septic shock and severe sepsis needs to be done rapidly and accurately to guide appropriate antibiotic therapy. Objective: The purpose of this study is to evaluate the accuracy of two diagnostic studies used in the emergency department (ED) to guide diagnosis of source of infection in this patient population. Methods: This was a retrospective review of ED patients admitted to an intensive care unit with the diagnosis of severe sepsis or septic shock over a 12-month period. We evaluated accuracy of initial microscopic urine analysis testing and chest radiography in the diagnosis of urinary tract infections and pneumonia, respectively. Results: Of the 1400 patients admitted to intensive care units, 170 patients met criteria for severe sepsis and septic shock. There were a total of 47 patients diagnosed with urinary tract infection, and their initial microscopic urine analysis with counts > 10 white blood cells were 80% sensitive (95% confidence interval [CI].66-.90) and 66% specific (95% CI.52-.77) for the positive final urine culture result. There were 85 patients with final diagnosis of pneumonia. The sensitivity and specificity of initial chest radiography were, respectively, 58% (95% CI.46-.68) and 91% (95% CI.81-.95) for the diagnosis of pneumonia. Conclusion: In patients with severe sepsis and septic shock, the chest radiograph has low sensitivity of 58%, whereas urine analysis has a low specificity of 66%. Given the importance of appropriate antibiotic selection and optimal but not perfect test characteristics, this population may benefit from broad-spectrum antibiotics, rather than antibiotics tailored toward a particular source of infection. Published by Elsevier Inc. C1 [Capp, Roberta; Chang, Yuchiao; Brown, David F. M.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02115 USA. [Capp, Roberta; Chang, Yuchiao; Brown, David F. M.] Harvard Univ, Sch Med, Boston, MA USA. [Capp, Roberta; Chang, Yuchiao; Brown, David F. M.] Massachusetts Gen Hosp, Brigham & Womens Hosp, Boston, MA 02115 USA. RP Capp, R (reprint author), Massachusetts Gen Hosp, Dept Emergency Med, 10 Neville House, Boston, MA 02115 USA. NR 18 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 0736-4679 J9 J EMERG MED JI J. Emerg. Med. PD JAN PY 2012 VL 42 IS 1 BP 52 EP 57 DI 10.1016/j.jemermed.2010.10.017 PG 6 WC Emergency Medicine SC Emergency Medicine GA 890KB UT WOS:000300142400010 PM 21215552 ER PT J AU Ehrmann, U Muth, CM Shank, E AF Ehrmann, Ulrich Muth, Claus-Martin Shank, Erik TI EHRMANN RESPONSE TO HAWKINS AND SEMPSROTT SO JOURNAL OF EMERGENCY MEDICINE LA English DT Letter C1 [Ehrmann, Ulrich; Muth, Claus-Martin] Univ Ulm, Dept Anesthesiol, Ulm, Germany. [Shank, Erik] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesiol,Div Pediat Anesthesia, Boston, MA USA. RP Ehrmann, U (reprint author), Univ Ulm, Dept Anesthesiol, Ulm, Germany. 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 0736-4679 J9 J EMERG MED JI J. Emerg. Med. PD JAN PY 2012 VL 42 IS 1 BP 67 EP 67 DI 10.1016/j.jemermed.2011.03.018 PG 1 WC Emergency Medicine SC Emergency Medicine GA 890KB UT WOS:000300142400017 ER PT J AU Driver, JA AF Driver, Jane A. TI Understanding the link between cancer and neurodegeneration SO JOURNAL OF GERIATRIC ONCOLOGY LA English DT Review DE Neurodegenerative disease; Cancer; Alzheimer's disease; Parkinson's disease; Pin1; Cell cycle ID PROLYL ISOMERASE PIN1; DEPENDENT PROLINE ISOMERIZATION; APOLIPOPROTEIN-E POLYMORPHISM; ATAXIA-TELANGIECTASIA BRAIN; NEURONAL CELL-DEATH; ALZHEIMERS-DISEASE; PARKINSONS-DISEASE; BREAST-CANCER; DIFFERENTIAL EXPRESSION; COGNITIVE IMPAIRMENT AB There is growing evidence that cancer shares a number of biological pathways with common neurodegenerative diseases of aging. In epidemiologic studies, Parkinson's and Alzheimer's disease seem to be associated with a decreased cancer risk. Genes associated with neurodegeneration have important functions in protein folding and processing, but often play a role in the cell cycle. Activation and deregulation of the cell cycle is a core feature of both diseases; in the neuron, the end result is apoptosis, while in the malignant cell, it is uncontrolled proliferation. Successful aging requires a careful balance between the forces that promote tissue renewal and those that suppress the cell cycle. Proteins such as p53 and Pin1 might explain why some individuals are relatively protected from cancer but at increased risk of neurodegeneration. This article reviews the available epidemiologic evidence linking neurodegenerative disease and cancer, discusses the cellular pathways and genes which might account for this unexpected relationship, and explores the potential therapeutic implications of this area of research. (C) 2011 Elsevier Ltd. All rights reserved. C1 [Driver, Jane A.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Aging,Dept Med, Boston, MA 02120 USA. [Driver, Jane A.] Harvard Univ, New England Geriatr Res Educ & Clin Ctr, VA Boston Healthcare Syst, Sch Med, Boston, MA 02120 USA. RP Driver, JA (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Aging,Dept Med, 1620 Tremont St, Boston, MA 02120 USA. EM jdriver@partners.org FU Veteran's Administration Career Development Award; Parkinson's Disease Foundation; Hartford Foundation; Harvard Medical School FX Dr. Driver is funded by a Veteran's Administration Career Development Award, and is a past recipient of grants from the Parkinson's Disease Foundation, the Hartford Foundation and Harvard Medical School. She has no conflicts of interest to disclose. NR 123 TC 18 Z9 18 U1 0 U2 12 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1879-4068 J9 J GERIATR ONCOL JI J. Geriatr. Oncol. PD JAN PY 2012 VL 3 IS 1 BP 58 EP 67 DI 10.1016/j.jgo.2011.11.007 PG 10 WC Oncology; Geriatrics & Gerontology SC Oncology; Geriatrics & Gerontology GA 889JN UT WOS:000300070100008 ER PT J AU Rosendorff, C Go, O Schmeidler, J Silverman, JM Beeri, MS AF Rosendorff, Clive Go, Orson Schmeidler, James Silverman, Jeremy M. Beeri, Michal S. TI Correlation of arterial blood pressure and compliance with left ventricular structure and function in the very elderly SO JOURNAL OF THE AMERICAN SOCIETY OF HYPERTENSION LA English DT Article DE Blood pressure; arterial stiffness; arterial compliance; myocardial remodeling; left ventricular hypertrophy; elderly ID PULSE CONTOUR ANALYSIS; PRESERVED EJECTION FRACTION; HEART-FAILURE; TISSUE DOPPLER; LOW PREVALENCE; WAVE VELOCITY; HYPERTENSION; AGE; IMPACT; ECHOCARDIOGRAPHY AB There are very few data on the relationship between systolic blood pressure (SBP), diastolic blood pressure (DBP), arterial compliance, and left ventricular structure and function, particularly left ventricular hypertrophy (LVH), in the very elderly (>75 years). SBP and arterial stiffness increase with age, and the question is: which of the two is the main stimulus to LVH? This is a cross-sectional study to compare blood pressure and arterial stiffness measures with regard to their correlations with echocardiographic parameters of LV structure and function, controlling for age and cardiovascular risk factors, in a very elderly population. Arterial stiffness was determined by radial pulse waveform using pulse contour analysis. LV dimensions were measured by transthoracic M-mode echocardiography, and diastolic function by tissue Doppler measurements of diastolic mitral annular velocities. There were 179 subjects, all male, with a mean age of 81.8 years. Using age-adjusted partial correlations, SBP, DBP, and mean arterial pressure (MAP) were correlated with parameters of LV structure and function. Correlation coefficients were: SBP versus left ventricular mass index (LVMI), r = 0.246; SBP versus early diastolic mitral annular velocity (MAV), r = 0.179; DBP versus LVMI, r = 0.199; DBP versus MAV, r = 0.199; MAP versus LVMI, r = 0.276; and MAP versus MAV, r = 0.206, all with P <.05. However, neither capacitative nor reflective arterial compliance was significantly correlated with any parameter of LV structure and function. After controlling for age and 10 cardiovascular and metabolic risk factors, the correlation between blood pressure and the measured LV parameters was substantially unchanged, as was the lack of correlation between indices of arterial compliance and the LV indices. Arterial blood pressure is correlated with LV structure and function in the very elderly, but arterial stiffness, as measured by diastolic pulse contour analysis, is not. J Am Soc Hypertens 2012;6(1):48-55. Published by Elsevier Inc on behalf of American Society of Hypertension. C1 [Rosendorff, Clive; Go, Orson] James J Peters VA Med Ctr, Dept Med, Bronx, NY 10468 USA. [Rosendorff, Clive] Mt Sinai Sch Med, Dept Med Cardiol, New York, NY USA. [Schmeidler, James; Silverman, Jeremy M.; Beeri, Michal S.] Mt Sinai Sch Med, Dept Psychiat, New York, NY USA. RP Rosendorff, C (reprint author), James J Peters VA Med Ctr, Dept Med, 130 W Kingsbridge Rd, Bronx, NY 10468 USA. EM clive.rosendorff@va.gov FU National Institute of Aging of the National Institutes of Health [AGO-02219] FX Supported by a Program Project Grant from the National Institute of Aging of the National Institutes of Health (AGO-02219), "Clinical and Biological Studies of Early Alzheimer's Disease; Project 4: Age at Onset and Cardiovascular Risk Factors in Very Late Onset Cognitive Decline and Alzheimer's Disease." NR 40 TC 2 Z9 3 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1933-1711 J9 J AM SOC HYPERTENS JI J. Am. Soc. Hypertens. PD JAN-FEB PY 2012 VL 6 IS 1 BP 48 EP 55 DI 10.1016/j.jash.2011.10.004 PG 8 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 887XQ UT WOS:000299965800006 PM 22243840 ER PT J AU Goodney, PP Wallaert, JB Scali, ST Stone, DH Patel, V Shaw, P Nolan, BW Cronenwett, JL AF Goodney, Philip P. Wallaert, Jessica B. Scali, Salvatore T. Stone, David H. Patel, Virendra Shaw, Palma Nolan, Brian W. Cronenwett, Jack L. CA Vasc Study Grp New England TI Impact of practice patterns in shunt use during carotid endarterectomy with contralateral carotid occlusion SO JOURNAL OF VASCULAR SURGERY LA English DT Article; Proceedings Paper CT Vascular Annual Meeting of the Society-for-Vascular-Surgery/Plenary Session of William von Liebig Forum/36th Annual Meeting of the Peripheral-Vascular-Surgery-Society CY JUN 15-18, 2011 CL Chicago, IL SP Soc Vasc Surg, Peripheral Vasc Surg Soc ID NORTHERN NEW-ENGLAND; ARTERY OCCLUSION; INTRAOPERATIVE CHOLANGIOGRAPHY; HIGHER RISK; ROUTINE; STENOSIS; QUALITY; TRIAL; SAFE AB Purpose: This study investigated the association between surgeon practice pattern in shunt placement and 30-day stroke/death in patients undergoing carotid endarterectomy (CEA) with contralateral carotid occlusion (CCO). Methods: Among 6379 CEAs performed in the Vascular Study Group of New England (VSGNE) between 2002 and 2009, we identified 353 patients who underwent CEA with CCO and compared the 30-day stroke/death rate with 5279 patients who underwent primary, isolated CEA with a patent contralateral carotid artery. Within patients with CCO, we examined the 30-day stroke/death rate across the reason for shunt placement and two distinct surgeon practice patterns in shunt placement: surgeons who selectively used a shunt (<= 95% of CEAs) or routinely used a shunt (>95% of CEAs). We used observed/expected (O/E) ratios to provide risk-adjusted comparisons across groups. Results: Of 353 patients with CCO, 118 (33%) underwent CEA without a shunt, 173 (49%) underwent CEA using a shunt placed routinely, and 62 (18%) had a shunt placed for a neurologic indication. Rates of 30-day stroke/death across categories of reason for shunt use were no shunt, 3.4%; routine shunt, 4.0%; and shunt for indication, 4.8% (P = .891). The risk of 30-day stroke/death was higher for surgeons who selectively placed shunts (5.6%) in all their CEAs and lower for surgeons who routinely placed shunts (1.5%, P = .05). The risk of 30-day stroke/death was >1 in patients undergoing selective shunting (O/E ratio, 1.4; 95% confidence interval [CI], 1.1-1.7) and <1 for surgeons who placed shunts routinely (O/E ratio, 0.4; 95% CI, 0.2-0.9). Stroke/death rates were lowest when individual surgeons' intraoperative decisions reflected their usual pattern of practice: 1.5% stroke/death rate when "routine" surgeons placed a shunt, 3.4% when "selective" surgeons did not place a shunt, and 7.6% stroke/death rate for "selective" surgeons who placed a shunt (P = .05 for trend). Conclusions: The risk of 30-day stroke/death is higher in CEA in patients with CCO than with a patent contralateral carotid artery. Surgeons who place shunts selectively during CEA have higher rates of stroke/death in patients with CCO. This suggests that shunt use for CCO during CEA is associated with fewer complications, but only if the surgeon uses a shunt as part of his or her routine practice in CEA. Surgeons should preoperatively consider their own practice pattern in shunt use when faced with a patient who may require shunt placement. (J Vase Surg 2012;55:61-71.) C1 [Goodney, Philip P.; Wallaert, Jessica B.; Stone, David H.; Nolan, Brian W.; Cronenwett, Jack L.] Dartmouth Hitchcock Med Ctr, Vasc Surg Sect, Lebanon, NH 03766 USA. [Goodney, Philip P.; Nolan, Brian W.; Cronenwett, Jack L.] Dartmouth Inst Hlth Policy & Clin Practice, Dartmouth Hitchcock Med Ctr, Hanover, NH USA. [Scali, Salvatore T.] Univ Florida, Sect Vasc & Endovasc Surg, Gainesville, FL USA. [Patel, Virendra] Massachusetts Gen Hosp, Vasc Surg Sect, Boston, MA 02114 USA. [Shaw, Palma] Brigham & Womens Hosp, Boston, MA 02115 USA. RP Goodney, PP (reprint author), Dartmouth Hitchcock Med Ctr, Vasc Surg Sect, 1 Med Ctr Dr, Lebanon, NH 03766 USA. EM philip.goodney@hitchcock.org FU NHLBI NIH HHS [1K08HL05676-01, K08 HL105676, K08 HL105676-02, K08 HL105676-01, K08 HL105676-03]; NIMHD NIH HHS [L32 MD006323] NR 40 TC 27 Z9 29 U1 0 U2 3 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0741-5214 J9 J VASC SURG JI J. Vasc. Surg. PD JAN PY 2012 VL 55 IS 1 BP 61 EP 71 DI 10.1016/j.jvs.2011.07.046 PG 11 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 871YF UT WOS:000298772900009 PM 22051863 ER PT J AU Spencer, J Amin, J Boddiboyena, R Packham, G Cavell, BE Alwi, SSS Paranal, RM Heightman, TD Wang, MH Marsden, B Coxhead, P Guille, M Tizzard, GJ Coles, SJ Bradner, JE AF Spencer, John Amin, Jahangir Boddiboyena, Ramesh Packham, Graham Cavell, Breeze E. Alwi, Sharifah S. Syed Paranal, Ronald M. Heightman, Tom D. Wang, Minghua Marsden, Brian Coxhead, Peter Guille, Matthew Tizzard, Graham J. Coles, Simon J. Bradner, James E. TI Click JAHAs: conformationally restricted ferrocene-based histone deacetylase inhibitors SO MEDCHEMCOMM LA English DT Article ID CHEMISTRY; DRUG AB A small library of ferrocene-based 1,2,3-triazole-containing hydroxamic acids has been synthesised employing click chemistry: 7-(4-ferrocenyl-1H-1,2,3-triazol-1-yl)-N-hydroxyheptanamide, 4b, containing the 1,2,3-triazole moiety adjacent to the ferrocene group, displayed excellent HDAC inhibition and activity in cells, inhibiting the deacetylation of tubulin as well as inducing cell cycle arrest. C1 [Spencer, John; Amin, Jahangir; Boddiboyena, Ramesh] Univ Greenwich Medway, Sch Sci, Chatham ME4 4TB, Kent, England. [Packham, Graham; Cavell, Breeze E.; Alwi, Sharifah S. Syed] Univ Southampton, Fac Med, Southampton Gen Hosp, Canc Res UK Ctr, Southampton SO16 6YD, Hants, England. [Paranal, Ronald M.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Heightman, Tom D.; Wang, Minghua; Marsden, Brian] Univ Oxford, Struct Genom Consortium, Oxford OX3 7DQ, England. [Coxhead, Peter; Guille, Matthew] Univ Portsmouth, Sch Biol Sci, Portsmouth PO1 2DT, Hants, England. [Tizzard, Graham J.; Coles, Simon J.] Univ Southampton, Sch Chem, UK Natl Crystallog Serv, Southampton SO17 1BJ, Hants, England. RP Spencer, J (reprint author), Univ Greenwich Medway, Sch Sci, Cent Ave, Chatham ME4 4TB, Kent, England. EM j.spencer@gre.ac.uk RI Coles, Simon/A-1795-2009; spencer, john/C-2156-2008; Tizzard, Graham/D-1227-2010; OI Coles, Simon/0000-0001-8414-9272; spencer, john/0000-0001-5231-8836; Syed Alwi, Sharifah Sakinah/0000-0002-6497-706X FU Greenwich University (GRE); CRUK; Malaysian Government; Biochemical and Biophysical Sciences Research Council; University of Southampton; Watercress Alliance; Multiple Myeloma Research Foundation; National Institutes of Health; EPSRC; Canadian Institutes for Health Research; Canadian Foundation for Innovation; Genome Canada through the Ontario Genomics Institute; GlaxoSmithKline; Karolinska Institutet; Knut and Alice Wallenberg Foundation; Ontario Innovation Trust; Ontario Ministry for Research and Innovation; Merck Co Inc.; Novartis Research Foundation; Swedish Agency for Innovation Systems; Swedish Foundation for Strategic Research; Wellcome Trust FX Greenwich University (GRE and the Alumni fund), BP are thanked for financial assistance (J.S. and J.A., for equipment), CRUK (G.P.), the Malaysian Government (S.S.S.A.), the Biochemical and Biophysical Sciences Research Council, University of Southampton and the Watercress Alliance (B.E. C.). J.E.B. and R.M.P. are supported by grants from the Multiple Myeloma Research Foundation and the National Institutes of Health. S.J.C. and G.J.T. would like to thank the EPSRC for funding. The EPSRC National Mass Spectrometry Service Centre (Swansea University) is thanked for HRMS measurements. Jose de Jesus Cazares Marinero, ENSCP (Paris), is thanked for helping rename our ferrocene compounds. The Structural Genomics Consortium is a registered charity (number 1097737) that receives funds from the Canadian Institutes for Health Research, the Canadian Foundation for Innovation, Genome Canada through the Ontario Genomics Institute, GlaxoSmithKline, Karolinska Institutet, the Knut and Alice Wallenberg Foundation, the Ontario Innovation Trust, the Ontario Ministry for Research and Innovation, Merck & Co Inc., the Novartis Research Foundation, the Swedish Agency for Innovation Systems, the Swedish Foundation for Strategic Research, and the Wellcome Trust. NR 14 TC 27 Z9 27 U1 1 U2 7 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 2040-2503 J9 MEDCHEMCOMM JI MedChemComm PD JAN PY 2012 VL 3 IS 1 BP 61 EP 64 DI 10.1039/c1md00203a PG 4 WC Biochemistry & Molecular Biology; Chemistry, Medicinal SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy GA 888AD UT WOS:000299975300010 ER PT J AU Glasser, JR Mallampalli, RK AF Glasser, Jennifer R. Mallampalli, Rama K. TI Surfactant and its role in the pathobiology of pulmonary infection SO MICROBES AND INFECTION LA English DT Review DE Surfactant; Collectin; Phospholipid; Infection ID ACUTE LUNG INJURY; RESPIRATORY-DISTRESS-SYNDROME; INNATE HOST-DEFENSE; PROTEIN-A; APOPTOTIC MIMICRY; II PNEUMOCYTES; VIRUS ENTRY; SP-C; COLLECTINS; DISEASE AB Pulmonary surfactant is a complex surface-active substance comprised of key phospholipids and proteins that has many essential functions. Surfactant's unique composition is integrally related to its surface-active properties, its critical role in host defense, and emerging immunomodulatory activities ascribed to surfactant lipids. Together these effector functions provide for lung stability and protection from a barrage of potentially virulent infectious pathogens. (C) 2011 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved. C1 [Glasser, Jennifer R.; Mallampalli, Rama K.] Acute Lung Injury Ctr Excellence, Dept Med, Pittsburgh, PA 15213 USA. [Mallampalli, Rama K.] Univ Pittsburgh, Dept Cell Biol & Physiol, Pittsburgh, PA 15213 USA. [Mallampalli, Rama K.] Vet Affairs Pittsburgh Healthcare Syst, Med Specialty Serv Line, Pittsburgh, PA 15213 USA. RP Mallampalli, RK (reprint author), PACCM, Dept Med, NW628 Montefiore,3459 5th Ave, Pittsburgh, PA 15213 USA. EM mallampallirk@upmc.edu FU US Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Biomedical Laboratory Research and Development; US Department of Veterans Affairs; National Institutes of Health [HL096376, HL097376, HL098174] FX We thank Ms. Tiffany Coon for critical review of the manuscript and helpful suggestions. This material is based upon work supported, in part, by the US Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Biomedical Laboratory Research and Development. This work was supported by a Merit Review Award from the US Department of Veterans Affairs and National Institutes of Health R01 grants HL096376, HL097376 and HL098174 (to R.K.M.). The contents presented do not represent the views of the Department of Veterans Affairs or the United States Government. NR 67 TC 19 Z9 23 U1 1 U2 18 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1286-4579 J9 MICROBES INFECT JI Microbes Infect. PD JAN PY 2012 VL 14 IS 1 BP 17 EP 25 DI 10.1016/j.micinf.2011.08.019 PG 9 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 888UO UT WOS:000300030300003 PM 21945366 ER PT J AU Biffi, A Shulman, JM Jagiella, JM Cortellini, L Ayres, AM Schwab, K Brown, DL Silliman, SL Selim, M Worrall, BB Meschia, JF Slowik, A De Jager, PL Greenberg, SM Schneider, JA Bennett, DA Rosand, J AF Biffi, A. Shulman, J. M. Jagiella, J. M. Cortellini, L. Ayres, A. M. Schwab, K. Brown, D. L. Silliman, S. L. Selim, M. Worrall, B. B. Meschia, J. F. Slowik, A. De Jager, P. L. Greenberg, S. M. Schneider, J. A. Bennett, D. A. Rosand, J. TI Genetic variation at CR1 increases risk of cerebral amyloid angiopathy SO NEUROLOGY LA English DT Article ID GENOME-WIDE ASSOCIATION; ALZHEIMERS-DISEASE; INTRACEREBRAL HEMORRHAGE; COGNITIVE IMPAIRMENT; IDENTIFIES VARIANTS; CLU; WINNERS; LINKAGE; DESIGN; COHORT AB Objective: Accumulated evidence suggests that a variant within the CR1 gene (single nucleotide polymorphism rs6656401), known to increase risk for Alzheimer disease (AD), influences beta-amyloid (A beta) deposition in brain tissue. Given the biologic overlap between AD and cerebral amyloid angiopathy (CAA), a leading cause of intracerebral hemorrhage (ICH) in elderly individuals, we investigated whether rs6656401 increases the risk of CAA-related ICH and influences vascular A beta deposition. Methods: We performed a case-control genetic association study of 89 individuals with CAArelated ICH and 280 individuals with ICH unrelated to CAA and compared them with 324 ICHfree control subjects. We also investigated the effect of rs6656401 on risk of recurrent CAA-ICH in a prospective longitudinal cohort of ICH survivors. Finally, association with severity of histopathologic CAA was investigated in 544 autopsy specimens from 2 longitudinal studies of aging. Results: rs6656401 was associated with CAA-ICH (odds ratio [OR] = 1.61, 95% confidence interval [CI] 1.19-2.17, p = 8.0 x 10(-4)) as well as with risk of recurrent CAA-ICH (hazard ratio = 1.35, 95% CI 1.04-1.76, p = 0.024). Genotype at rs6656401 was also associated with severity of CAA pathology at autopsy (OR = 1.34, 95% CI 1.05-1.71, rho = 0.009). Adjustment for parenchymal amyloid burden did not cancel this effect, suggesting that, despite the correlation between parenchymal and vascular amyloid pathology, CR1 acts independently on both processes, thus increasing risk of both AD and CAA. Conclusion: The CR1 variant rs6656401 influences risk and recurrence of CAA-ICH, as well as the severity of vascular amyloid deposition. Neurology (R) 2012;78:334-341 C1 [Biffi, A.; Cortellini, L.; Rosand, J.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Biffi, A.; Cortellini, L.; Ayres, A. M.; Schwab, K.; Greenberg, S. M.; Rosand, J.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Biffi, A.; Shulman, J. M.; Cortellini, L.; De Jager, P. L.; Rosand, J.] Broad Inst, Program Med & Populat Genet, Cambridge, MA USA. [Shulman, J. M.; De Jager, P. L.] Brigham & Womens Hosp, Dept Neurol, Program Translat NeuroPsychiat Genom, Inst Neurosci, Boston, MA 02115 USA. [Shulman, J. M.; De Jager, P. L.] Brigham & Womens Hosp, Dept Psychiat, Program Translat NeuroPsychiat Genom, Inst Neurosci, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. [Jagiella, J. M.] Jagiellonian Univ Med Coll, Dept Neurol, Krakow, Poland. [Brown, D. L.] Univ Michigan Hlth Syst, Dept Neurol, Stroke Program, Ann Arbor, MI USA. [Silliman, S. L.] Univ Florida, Dept Neurol, Coll Med, Jacksonville, FL USA. [Selim, M.] Beth Israel Deaconess Med Ctr, Dept Neurol, Boston, MA 02215 USA. [Worrall, B. B.] Univ Virginia Hlth Syst, Dept Neurol & Publ Hlth Sci, Charlottesville, VA USA. [Meschia, J. F.] Mayo Clin, Dept Neurol, Jacksonville, FL 32224 USA. [Schneider, J. A.; Bennett, D. A.] Rush Univ, Med Ctr, Dept Neurol Sci, Rush Alzheimers Dis Ctr, Chicago, IL 60612 USA. RP Rosand, J (reprint author), Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. EM jrosand@partners.org OI Brown, Devin/0000-0002-9815-3421 FU Edward and Maybeth Sonn Research Fund; University of Michigan General Clinical Research Center [M01-RR000042]; National Institute for Neurologic Disorders and Stroke [R01-NS063925, R01-NS059727, P50-NS051343, K23-NS064052, K23-NS059774]; National Institute on Aging [R01-AG026484]; American Heart Association/Bugher Foundation Centers for Stroke Prevention Research [0775011N, 0755984T]; NIH [R01-AG30146, R01-AG179917, R01-AG15819, P30-AG10161, K08-AG0344290]; American Heart Association Bugher Foundation; NIH/NIA; Beth Israel Deaconess Medical Center and Harvard/MIT Health Sciences and Technology; Pfizer Inc; Merck Co, Inc.; Parkinson's Study Group; Harvard NeuroDiscovery Center/Massachusetts Alzheimer's Disease Research Center; Burroughs Wellcome Fund; NIH/NINDS; NIH; NIH (NINDS, NIA); NINDS [K23 NS051202]; CVR Global, Inc.; University of Michigan; Michigan Department of Community Health; Blue Cross Blue Shield of Michigan Foundation; Diocese of Corpus Christi; NIH (NINDS, NHLBI); Biogen Idec; Novartis; Genzyme Corporation; Schering-Plough Corp.; Mitsubishi Tanabe Pharma Corporation; Avanir Pharmaceuticals; NIH (NHGRI, NHLBI, NINDS); University of Virginia-CTSA; Alzheimer's Association; American Heart Association-Bugher Foundation; MGH Deane Institute for Integrative Research in Atrial Fibrillation and Stroke FX The GOCHA study was supported by the Edward and Maybeth Sonn Research Fund, the University of Michigan General Clinical Research Center (M01-RR000042), the National Institute for Neurologic Disorders and Stroke (R01-NS063925, R01-NS059727, P50-NS051343, K23-NS064052, and K23-NS059774) and the National Institute on Aging (R01-AG026484). Dr. Biffi received support from the American Heart Association/Bugher Foundation Centers for Stroke Prevention Research (0775011N, 0755984T). The ROS and MAP studies are supported by NIH grants (R01-AG30146, R01-AG179917, R01-AG15819, P30-AG10161, and K08-AG0344290).; Dr. Biffi receives research support from the American Heart Association Bugher Foundation. Dr. Shulman receives research support from the NIH/NIA, the Clinical Investigator Training Program: Beth Israel Deaconess Medical Center and Harvard/MIT Health Sciences and Technology, in collaboration with Pfizer Inc and Merck & Co, Inc., Parkinson's Study Group, Harvard NeuroDiscovery Center/Massachusetts Alzheimer's Disease Research Center, and Burroughs Wellcome Fund, Career Award for Medical Scientists. Dr. Jagiella reports no disclosures. L. Cortellini receives research support from the NIH/NINDS. A. M. Ayres receives research support from the NIH. K. Schwab receives research support from the NIH (NINDS, NIA). Dr. Brown serves on the editorial board of Neurology (R); is supported by an NINDS Career Development Award (K23 NS051202); and has received research support from CVR Global, Inc., the University of Michigan, Michigan Department of Community Health, Blue Cross Blue Shield of Michigan Foundation, the Diocese of Corpus Christi, and the NIH. Dr. Brown has received speaker honoraria from the Hazel K. Goddess Fund for Stroke Research in Women and receives research support from the NIH (NINDS, NHLBI). Dr. Silliman serves on the speakers' bureau for and has received speaker honoraria from Biogen Idec and has received research support from Biogen Idec, Novartis, Genzyme Corporation, Schering-Plough Corp., and the NIH/NINDS. Dr. Selim serves on scientific advisory boards for Mitsubishi Tanabe Pharma Corporation and Avanir Pharmaceuticals; serves as Controversies Section Co-editor for Stroke; receives publishing royalties for The Stroke Book (Cambridge University Press, 2007) and Neurology Emergencies (Oxford University Press, 2011); and receives research support from the NIH. Dr. Worrall serves as an Associate Editor of Neurology (R) and on the editorial board of Seminars in Neurology; receives royalties from the publication of Merritt's Neurology, 10th, 11th, and 12th eds. (chapter author); and receives/has received research support from the NIH (NHGRI, NHLBI, NINDS) and from the University of Virginia-CTSA Pilot Project. Dr. Meschia serves on the editorial boards of Stroke and the Journal of Stroke and Cerebrovascular Diseases and receives research support from the NIH/NINDS. Dr. Slowik reports no disclosures Dr. De Jager has served on scientific advisory boards for Teva Pharmaceutical Industries Ltd. and Biogen Idec; has received speaker honoraria from Biogen Idec; serves on the editorial board of Journal of Neuroimmunology; and receives research support from Biogen Idec and the NIH. Dr. Greenberg serves on a data safety monitoring board for the NIH/NINDS; has received speaker honoraria from Esteve, Medtronics, Inc., and Pfizer Inc; serves on the editorial boards of Neurology (R), Stroke, Cerebrovascular Disease, and the Journal of Alzheimer's Disease and Other Dementias; has served as a consultant for Roche, Janssen Alzheimer Immunotherapy, and Bristol-Myers Squibb; and has received/receives research support from the NIH and the Alzheimer's Association. Dr. Schneider served on a scientific advisory board for GE Healthcare; serves as Monitoring Editor for the Journal Histochemistry and Cytochemistry, on the editorial board of the International Journal of Clinical and Experimental Pathology, and as Associate Editor for the Journal of Alzheimer's Disease; serves as a consultant for Avid Radiopharmaceuticals, Inc.; and receives research support from Avid Radiopharmaceuticals, Inc. and the NIH. Dr.; Bennett serves on the editorial boards of eurology (R), Neuroepidemiology, and Current Alzheimer's Research; serves on the scientific advisory board for Vigorous Minds; serves/has served as a consultant to Schering-Plough Corp., Double Helix Development, Medivation, Inc., Danone Research B. V., and Gerson Lehrman Group; and receives research support from Danone Research B. V., the NIH, the Illinois Department of Public Health, and the Robert C. Borwell Endowment Fund. Dr. Rosand receives research support from the NIH (NINDS, NHLBI), the American Heart Association-Bugher Foundation, and the MGH Deane Institute for Integrative Research in Atrial Fibrillation and Stroke. NR 31 TC 36 Z9 41 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD JAN PY 2012 VL 78 IS 5 BP 334 EP 341 DI 10.1212/WNL.0b013e3182452b40 PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA 888YJ UT WOS:000300040300013 PM 22262751 ER PT J AU Kotton, CN Poznansky, MC AF Kotton, Camille N. Poznansky, Mark C. TI Vaccination of Oncology Patients: An Effective Tool and an Opportunity Not to Be Missed SO ONCOLOGIST LA English DT Editorial Material ID TRANSPLANT RECIPIENTS; INFLUENZA; H1N1; RECOMMENDATIONS C1 [Poznansky, Mark C.] Harvard Univ, Sch Med, Vaccine & Immunotherapy Ctr, Massachusetts Gen Hosp E,Infect Dis Div, Charlestown, MA 02129 USA. [Kotton, Camille N.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Kotton, Camille N.; Poznansky, Mark C.] Harvard Univ, Sch Med, Boston, MA USA. RP Poznansky, MC (reprint author), Harvard Univ, Sch Med, Vaccine & Immunotherapy Ctr, Massachusetts Gen Hosp E,Infect Dis Div, 13th St, Charlestown, MA 02129 USA. EM mpoznansky@partners.org RI Inov Farmaceutica, Inct/K-2313-2013 NR 12 TC 2 Z9 2 U1 0 U2 4 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1083-7159 J9 ONCOLOGIST JI Oncologist PD JAN PY 2012 VL 17 IS 1 BP 1 EP 2 DI 10.1634/theoncologist.2011-0383 PG 2 WC Oncology SC Oncology GA 887UG UT WOS:000299955500001 PM 22240542 ER PT J AU Borger, DR Tanabe, KK Fan, KC Lopez, HU Fantin, VR Straley, KS Schenkein, DP Hezel, AF Ancukiewicz, M Liebman, HM Kwak, EL Clark, JW Ryan, DP Deshpande, V Dias-Santagata, D Ellisen, LW Zhu, AX Iafrate, AJ AF Borger, Darrell R. Tanabe, Kenneth K. Fan, Kenneth C. Lopez, Hector U. Fantin, Valeria R. Straley, Kimberly S. Schenkein, David P. Hezel, Aram F. Ancukiewicz, Marek Liebman, Hannah M. Kwak, Eunice L. Clark, Jeffrey W. Ryan, David P. Deshpande, Vikram Dias-Santagata, Dora Ellisen, Leif W. Zhu, Andrew X. Iafrate, A. John TI Frequent Mutation of Isocitrate Dehydrogenase (IDH)1 and IDH2 in Cholangiocarcinoma Identified Through Broad-Based Tumor Genotyping SO ONCOLOGIST LA English DT Article DE Biliary tract cancer; Cholangiocarcinoma; IDH1; IDH2; 2-Hydroxyglutarate; Mutation ID ACUTE MYELOID-LEUKEMIA; CELL LUNG-CANCER; BILIARY-TRACT; K-RAS; GALLBLADDER CARCINOMA; GENE-MUTATIONS; CODON 132; GLIOMAS; 2-HYDROXYGLUTARATE; ASSOCIATION AB Cancers of origin in the gallbladder and bile ducts are rarely curable with current modalities of cancer treatment. Our clinical application of broad-based mutational profiling for patients diagnosed with a gastrointestinal malignancy has led to the novel discovery of mutations in the gene encoding isocitrate dehydrogenase 1 (IDH1) in tumors from a subset of patients with cholangiocarcinoma. A total of 287 tumors from gastrointestinal cancer patients (biliary tract, colorectal, gastroesophageal, liver, pancreatic, and small intestine carcinoma) were tested during routine clinical evaluation for 130 site-specific mutations within 15 cancer genes. Mutations were identified within a number of genes, including KRAS (35%), TP53 (22%), PIK3CA (10%), BRAF (7%), APC (6%), NRAS (3%), AKT1 (1%), CTNNB1 (1%), and PTEN (1%). Although mutations in the metabolic enzyme IDH1 were rare in the other common gastrointestinal malignancies in this series (2%), they were found in three tumors (25%) of an initial series of 12 biliary tract carcinomas. To better define IDH1 and IDH2 mutational status, an additional 75 gallbladder and bile duct cancers were examined. Combining these cohorts of biliary cancers, mutations in IDH1 and IDH2 were found only in cholangiocarcinomas of intrahepatic origin (nine of 40, 23%) and in none of the 22 extrahepatic cholangiocarcinomas and none of the 25 gallbladder carcinomas. In an analysis of frozen tissue specimens, IDH1 mutation was associated with highly elevated tissue levels of the enzymatic product 2-hydroxyglutarate. Thus, IDH1 mutation is a molecular feature of cholangiocarcinomas of intrahepatic origin. These findings define a specific metabolic abnormality in this largely incurable type of gastrointestinal cancer and present a potentially new target for therapy. The Oncologist 2012; 17: 72-79 C1 [Iafrate, A. John] Massachusetts Gen Hosp, Pathol Serv, Ctr Canc, Dept Pathol, Boston, MA 02114 USA. [Borger, Darrell R.; Fan, Kenneth C.; Lopez, Hector U.; Ancukiewicz, Marek; Liebman, Hannah M.; Kwak, Eunice L.; Clark, Jeffrey W.; Ryan, David P.; Ellisen, Leif W.; Zhu, Andrew X.] Massachusetts Gen Hosp, Div Hematol Oncol, Ctr Canc, Boston, MA 02114 USA. [Tanabe, Kenneth K.] Massachusetts Gen Hosp, Div Surg Oncol, Ctr Canc, Boston, MA 02114 USA. [Fantin, Valeria R.; Straley, Kimberly S.; Schenkein, David P.] Agios Pharmaceut, Cambridge, MA USA. [Hezel, Aram F.] Univ Rochester, Dept Med, Rochester, NY USA. [Borger, Darrell R.; Tanabe, Kenneth K.; Kwak, Eunice L.; Clark, Jeffrey W.; Ryan, David P.; Deshpande, Vikram; Dias-Santagata, Dora; Ellisen, Leif W.; Zhu, Andrew X.; Iafrate, A. John] Harvard Univ, Sch Med, Boston, MA USA. RP Iafrate, AJ (reprint author), Massachusetts Gen Hosp, Pathol Serv, Ctr Canc, Dept Pathol, 55 Fruit St,GRJ-1015, Boston, MA 02114 USA. EM aiafrate@partners.org RI Inov Farmaceutica, Inct/K-2313-2013 FU Amgen; Bayer; internal MGH Cancer Center FX Aram F. Hezel: Amgen, (H, RF); Andrew X. Zhu: Onyx, ImClone, Novartis, Pfizer, Sanofi (C/A); Bayer (RF); We thank Vanessa Scialabba and Jae Han for their technical assistance. We also thank Mohammad Miri for his assistance in tissue procurement from the MGH Tissue Repository, which was used in the metabolite analysis. This work was supported by internal MGH Cancer Center funds. NR 44 TC 195 Z9 198 U1 2 U2 22 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1083-7159 EI 1549-490X J9 ONCOLOGIST JI Oncologist PD JAN PY 2012 VL 17 IS 1 BP 72 EP 79 DI 10.1634/theoncologist.2011-0386 PG 8 WC Oncology SC Oncology GA 887UG UT WOS:000299955500011 PM 22180306 ER PT J AU Colpo, A Hochberg, E Chen, YB AF Colpo, Anna Hochberg, Ephraim Chen, Yi-Bin TI Current Status of Autologous Stem Cell Transplantation in Relapsed and Refractory Hodgkin's Lymphoma SO ONCOLOGIST LA English DT Article DE Autologous stem cell transplant; Hodgkin's lymphoma; High-dose chemotherapy ID HIGH-DOSE CHEMOTHERAPY; BONE-MARROW-TRANSPLANTATION; POSITRON-EMISSION-TOMOGRAPHY; TERM-FOLLOW-UP; PROGRESSION-FREE SURVIVAL; PROGNOSTIC-FACTORS; SALVAGE THERAPY; DISEASE PATIENTS; 1ST RELAPSE; SEQUENTIAL CHEMOTHERAPY AB Despite the relatively high long-term disease-free survival (DFS) rate for patients with Hodgkin lymphoma (HL) with modern combination chemotherapy or combined modality regimens, similar to 20% of patients die from progressive or relapsed disease. The standard treatment for relapsed and primary refractory HL is salvage chemotherapy followed by high-dose chemotherapy and autologous stem cell transplantation (ASCT), which has shown a 5-year progression-free survival rate of similar to 50%-60%. Recent developments in a number of diagnostic and therapeutic modalities have begun to improve these results. Functional imaging, refinement of clinical prognostic factors, and development of novel biomarkers have improved the predictive algorithms, allowing better patient selection and timing for ASCT. In addition, these algorithms have begun to identify a group of patients who are candidates for more aggressive treatment beyond standard ASCT. Novel salvage regimens may potentially improve the rate of complete remission prior to ASCT, and the use of maintenance therapy after ASCT has become a subject of current investigation. We present a summary of developments in each of these areas. The Oncologist 2012; 17: 80-90 C1 [Chen, Yi-Bin] Massachusetts Gen Hosp, Bone Marrow Transplant Unit, Div Hematol Oncol, Boston, MA 02114 USA. [Colpo, Anna] Univ Padua, Sch Med, Hematol & Clin Immunol Branch, Dept Clin & Expt Med, Padua, Italy. RP Chen, YB (reprint author), Massachusetts Gen Hosp, Bone Marrow Transplant Unit, Div Hematol Oncol, Cox 108,55 Fruit St, Boston, MA 02114 USA. EM ychen6@partners.org RI Inov Farmaceutica, Inct/K-2313-2013 FU Otsuka; Millennium; Bayer; Leukemia and Lymphoma Society FX Yi-Bin Chen: Genzyme (C/A); Otsuka, Millennium, Bayer (RF).; Dr. Chen is supported by a career development award in clinical research from the Leukemia and Lymphoma Society. NR 111 TC 9 Z9 9 U1 0 U2 2 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1083-7159 EI 1549-490X J9 ONCOLOGIST JI Oncologist PD JAN PY 2012 VL 17 IS 1 BP 80 EP 90 DI 10.1634/theoncologist.2011-0177 PG 11 WC Oncology SC Oncology GA 887UG UT WOS:000299955500012 PM 22210089 ER PT J AU Tanner, JM Chang, TI AF Tanner, Jeffrey M. Chang, Tina I. TI Syndrome Z: A comparison of prevalence between females and males SO SLEEP MEDICINE LA English DT Letter C1 [Tanner, Jeffrey M.; Chang, Tina I.] VA Greater Los Angeles Healthcare Syst, Oral & Maxillofacial Surg Sect, Dent Serv, Los Angeles, CA 90073 USA. [Chang, Tina I.] Univ Calif Los Angeles, Sch Dent, Los Angeles, CA 90024 USA. RP Chang, TI (reprint author), VA Greater Los Angeles Healthcare Syst, Oral & Maxillofacial Surg Sect, Dent Serv, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM tinachangdmdmd@gmail.com NR 5 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1389-9457 J9 SLEEP MED JI Sleep Med. PD JAN PY 2012 VL 13 IS 1 BP 119 EP 120 DI 10.1016/j.sleep.2011.06.005 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 890GA UT WOS:000300131900025 PM 21982339 ER PT J AU Ji, ZY Flaherty, KT Tsao, H AF Ji, Zhenyu Flaherty, Keith T. Tsao, Hensin TI Targeting the RAS pathway in melanoma SO TRENDS IN MOLECULAR MEDICINE LA English DT Review ID RECOMBINANT INTERLEUKIN-2 THERAPY; INHIBITOR AZD6244 ARRY-142886; KIT PROTEIN EXPRESSION; METASTATIC MELANOMA; CUTANEOUS MELANOMA; PHASE-II; IMATINIB MESYLATE; TUMOR-GROWTH; B-RAF; SELECTIVE INHIBITOR AB Metastatic melanoma is a highly lethal type of skin cancer and is often refractory to all traditional chemotherapeutic agents. Key insights into the genetic make-up of melanoma tumors have led to the development of promising targeted agents. An activated RAS pathway, anchored by oncogenic BRAF, appears to be the central motor driving melanoma proliferation. Although recent clinical trials have brought enormous hope to patients with melanoma, adverse effects and novel escape mechanisms of these inhibitors have already emerged. Definition of the limits of the first successful targeted therapies will provide the basis for further advances in management of disseminated melanoma. In this review, the current state of targeted therapy for melanoma is discussed, including the potent BRAF(V600E) inhibitor vemurafenib. C1 [Ji, Zhenyu; Tsao, Hensin] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Ji, Zhenyu; Tsao, Hensin] Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02114 USA. [Flaherty, Keith T.; Tsao, Hensin] Massachusetts Gen Hosp, MGH Canc Ctr, Boston, MA 02114 USA. RP Tsao, H (reprint author), Massachusetts Gen Hosp, Wellman Ctr Photomed, 55 Fruit St, Boston, MA 02114 USA. EM htsao@partners.org FU National Institutes of Health [K24 CA149202]; Melanoma Research Alliance; American Skin Association; Massachusetts General Hospital FX We want to thank the National Institutes of Health (K24 CA149202 to H.T.), the Melanoma Research Alliance, the American Skin Association and the generous donors to the Massachusetts General Hospital Millennium Melanoma Fund for their support during the writing of this review. NR 94 TC 33 Z9 33 U1 2 U2 14 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1471-4914 EI 1471-499X J9 TRENDS MOL MED JI Trends Mol. Med PD JAN PY 2012 VL 18 IS 1 BP 27 EP 35 DI 10.1016/j.molmed.2011.08.001 PG 9 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 887ZT UT WOS:000299974300005 PM 21962474 ER PT J AU Hyman, BT Phelps, CH Beach, TG Bigio, EH Cairns, NJ Carrillo, MC Dickson, DW Duyckaerts, C Frosch, MP Masliah, E Mirra, SS Nelson, PT Schneider, JA Thal, DR Thies, B Trojanowski, JQ Vinters, HV Montine, TJ AF Hyman, Bradley T. Phelps, Creighton H. Beach, Thomas G. Bigio, Eileen H. Cairns, Nigel J. Carrillo, Maria C. Dickson, Dennis W. Duyckaerts, Charles Frosch, Matthew P. Masliah, Eliezer Mirra, Suzanne S. Nelson, Peter T. Schneider, Julie A. Thal, Dietmar Rudolf Thies, Bill Trojanowski, John Q. Vinters, Harry V. Montine, Thomas J. TI National Institute on Aging-Alzheimer's Association guidelines for the neuropathologic assessment of Alzheimer's disease SO ALZHEIMERS & DEMENTIA LA English DT Article DE Alzheimer's disease; Lewy body disease; Vascular brain injury; Neuropathology; Consensus guidelines ID CEREBRAL AMYLOID ANGIOPATHY; LEWY BODY DISEASE; A-BETA-DEPOSITION; FRONTOTEMPORAL LOBAR DEGENERATION; VASCULAR COGNITIVE IMPAIRMENT; BRAINNET EUROPE CONSORTIUM; MEDIAL TEMPORAL-LOBE; NEUROFIBRILLARY TANGLES; DIAGNOSTIC GUIDELINES; HIPPOCAMPAL SCLEROSIS AB A consensus panel from the United States and Europe was convened recently to update and revise the 1997 consensus guidelines for the neuropathologic evaluation of Alzheimer's disease (AD) and other diseases of brain that are common in the elderly. The new guidelines recognize the pre-clinical stage of AD, enhance the assessment of AD to include amyloid accumulation as well as neurofibrillary change and neuritic plaques, establish protocols for the neuropathologic assessment of Lewy body disease, vascular brain injury, hippocampal sclerosis, and TDP-43 inclusions, and recommend standard approaches for the workup of cases and their clinico-pathologic correlation. (C) 2012 The Alzheimer's Association. All rights reserved. C1 [Montine, Thomas J.] Univ Washington, Sch Med, Dept Pathol, Seattle, WA 98195 USA. [Hyman, Bradley T.] Harvard Univ, Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02115 USA. [Phelps, Creighton H.] NIA, Bethesda, MD 20892 USA. [Beach, Thomas G.] Banner Sun Hlth Res Inst, Civin Lab Neuropathol, Sun City, AZ USA. [Bigio, Eileen H.] Northwestern Univ, Dept Pathol, NW Alzheimer Dis Ctr, Feinberg Sch Med, Chicago, IL 60611 USA. [Cairns, Nigel J.] Washington Univ, Sch Med, Dept Neurol, St Louis, MO 63110 USA. [Cairns, Nigel J.] Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO USA. [Carrillo, Maria C.; Thies, Bill] Alzheimers Assoc, Chicago, IL USA. [Dickson, Dennis W.] Mayo Clin, Dept Neurosci, Jacksonville, FL 32224 USA. [Duyckaerts, Charles] Hop La Pitie Salpetriere, Serv Neuropathol Raymond Escourolle, Paris, France. [Frosch, Matthew P.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, CS Kubik Lab Neuropathol, Boston, MA USA. [Masliah, Eliezer] Univ Calif San Diego, Sch Med, Dept Neurosci, La Jolla, CA 92093 USA. [Masliah, Eliezer] Univ Calif San Diego, Sch Med, Dept Pathol, La Jolla, CA 92093 USA. [Mirra, Suzanne S.] Suny Downstate Med Ctr, Dept Pathol, Brooklyn, NY 11203 USA. [Nelson, Peter T.] Univ Kentucky, Sanders Brown Ctr Aging, Lexington, KY 40536 USA. [Schneider, Julie A.] Rush Univ, Med Ctr, Rush Alzheimers Dis Ctr, Chicago, IL 60612 USA. [Schneider, Julie A.] Rush Univ, Med Ctr, Dept Pathol, Chicago, IL 60612 USA. [Schneider, Julie A.] Rush Univ, Med Ctr, Dept Neurol Sci, Chicago, IL 60612 USA. [Thal, Dietmar Rudolf] Univ Ulm, Inst Pathol, Neuropathol Lab, Ulm, Germany. [Trojanowski, John Q.] Univ Penn, Sch Med, Dept Pathol & Lab Med, Inst Aging,Ctr Neurodegenerat Dis Res, Philadelphia, PA 19104 USA. [Vinters, Harry V.] Univ Calif Los Angeles, Dept Pathol & Lab Med Neuropathol, Los Angeles, CA USA. [Vinters, Harry V.] Univ Calif Los Angeles, Dept Neurol, Los Angeles, CA 90024 USA. RP Montine, TJ (reprint author), Univ Washington, Sch Med, Dept Pathol, Seattle, WA 98195 USA. EM tmontine@uw.edu OI Dickson, Dennis W/0000-0001-7189-7917 FU NIH [AG05134, AG05136, AG03991, AG05681, AG24904, AG28383, AG10161, AG17917, AG10124, AG13854, AG19610, NS62684, AG16570, AG15819, AG12435, AG05131, AG016976, AG18840]; AA, Arizona Department of Health Services (Arizona Alzheimer's Consortium) [211002]; Deutsche Forschungsgemeinschaft (DFG) [TH-624-4-1]; Alzheimer Forschung Initiative (AFT) [10810]; Nancy and Buster Alvord Endowment; Charles and Joanne Knight Alzheimer Research Initiative FX Support was provided by the NIH (AG05134, AG05136, AG03991, AG05681, AG24904, AG28383, AG10161, AG17917, AG10124, AG13854, AG19610, NS62684, AG16570, AG15819, AG12435, AG05131, AG016976, and AG18840) as well as the AA, Arizona Department of Health Services (contract 211002, Arizona Alzheimer's Consortium), Deutsche Forschungsgemeinschaft (DFG TH-624-4-1) and Alzheimer Forschung Initiative (AFT #10810), the Nancy and Buster Alvord Endowment, and the Charles and Joanne Knight Alzheimer Research Initiative. The authors extend their deepest thanks to Dr. Heiko Braak, Dr. Kelly Del Tredici, Dr. Nina Silverberg, Dr. Walter Kukull, Dr. Kathleen Montine, Dr. Cerise Elliott, and Ms. Sarah Monsell for their valuable input. NR 106 TC 401 Z9 412 U1 6 U2 50 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1552-5260 J9 ALZHEIMERS DEMENT JI Alzheimers. Dement. PD JAN PY 2012 VL 8 IS 1 BP 1 EP 13 DI 10.1016/j.jalz.2011.10.007 PG 13 WC Clinical Neurology SC Neurosciences & Neurology GA 882TN UT WOS:000299586900001 PM 22265587 ER PT J AU Goodman, A AF Goodman, Annekathryn TI The Tensions and Challenges of Unpredictable Drug Shortages SO AMERICAN JOURNAL OF BIOETHICS LA English DT Editorial Material C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Goodman, A (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. EM agoodman@partners.org NR 5 TC 4 Z9 4 U1 0 U2 0 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 1526-5161 J9 AM J BIOETHICS JI Am. J. Bioeth. PY 2012 VL 12 IS 1 BP 20 EP 22 DI 10.1080/15265161.2012.634667 PG 5 WC Ethics; Medical Ethics; Social Issues; Social Sciences, Biomedical SC Social Sciences - Other Topics; Medical Ethics; Social Issues; Biomedical Social Sciences GA 885PC UT WOS:000299790200008 PM 22220954 ER PT J AU Karver, MR Weissleder, R Hilderbrand, SA AF Karver, Mark R. Weissleder, Ralph Hilderbrand, Scott A. TI Bioorthogonal Reaction Pairs Enable Simultaneous, Selective, Multi-Target Imaging SO ANGEWANDTE CHEMIE-INTERNATIONAL EDITION LA English DT Article DE azides; bioorthogonal reactions; cycloaddition; imaging; tetrazines ID FREE CLICK CHEMISTRY; LIVING CELLS; 1,3-DIPOLAR CYCLOADDITION; COPPER-FREE; PROBES; AZIDE C1 [Karver, Mark R.; Weissleder, Ralph; Hilderbrand, Scott A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Syst Biol, Boston, MA 02114 USA. RP Hilderbrand, SA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Syst Biol, 185 Cambridge St,Suite 5-210, Boston, MA 02114 USA. EM scott_hilderbrand@hms.harvard.edu FU NIH [RO1EB010011, P50A86355] FX The authors would like to thank Dr. Jack Szostak at MGH for the use of the stopped-flow spectrometer. The authors would also like to thank Alex Chudnovskiy, Elizabeth Tiglao, and Yoshi Iwamoto of CSB for technical assistance with cell culture and flow cytometry as well as Neal K. Devaraj and Jason R. McCarthy for helpful discussions. This research is supported in part by NIH grants RO1EB010011 and P50A86355. NR 34 TC 107 Z9 108 U1 4 U2 63 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA POSTFACH 101161, 69451 WEINHEIM, GERMANY SN 1433-7851 EI 1521-3773 J9 ANGEW CHEM INT EDIT JI Angew. Chem.-Int. Edit. PY 2012 VL 51 IS 4 BP 920 EP 922 DI 10.1002/anie.201104389 PG 3 WC Chemistry, Multidisciplinary SC Chemistry GA 877EB UT WOS:000299158700014 PM 22162316 ER PT J AU Iftimia, N Iyer, AK Hammer, DX Lue, N Mujat, M Pitman, M Ferguson, RD Amiji, M AF Iftimia, Nicusor Iyer, Arun K. Hammer, Daniel X. Lue, Niyom Mujat, Mircea Pitman, Martha Ferguson, R. Daniel Amiji, Mansoor TI Fluorescence-guided optical coherence tomography imaging for colon cancer screening: a preliminary mouse study SO BIOMEDICAL OPTICS EXPRESS LA English DT Article ID COLORECTAL-CANCER; APC(MIN/+) MOUSE; GASTRIC-CANCER; DIAGNOSIS; ENDOSCOPY; RESPONSES; CELLS; ACID AB A new concept for cancer screening has been preliminarily investigated. A cancer targeting agent loaded with a near-infrared (NIR) dye was topically applied on the tissue to highlight cancer-suspect locations and guide optical coherence tomography (OCT) imaging, which was used to further investigate tissue morphology at the micron scale. A pilot study on ApcMin mice has been performed to preliminarily test this new cancer screening approach. As a cancer-targeting agent, poly(epsilon-caprolactone) microparticles (PCLMPs), labeled with a NIR dye and functionalized with an RGD (argenine-glycine-aspartic acid) peptide, were used. This agent recognizes the alpha(nu)beta(3) integrin receptor (ABIR), which is over-expressed by epithelial cancer cells. The contrast agent was administered topically in vivo in mouse colon. After incubation, the animals were sacrificed and fluorescence-guided high resolution optical coherence tomography (OCT) imaging was used to visualize colon morphology. The preliminary results show preferential staining of the abnormal tissue, as indicated by both microscopy and laser-induced fluorescence imaging, and OCT's capability to differentiate between normal mucosal areas, early dysplasia, and adenocarcinoma. Although very preliminary, the results of this study suggest that fluorescence-guided OCT imaging might be a suitable approach for cancer screening. If successful, this approach could be used by clinicians to more reliably diagnose early stage cancers in vivo. (C) 2011 Optical Society of America C1 [Iftimia, Nicusor; Hammer, Daniel X.; Lue, Niyom; Mujat, Mircea; Ferguson, R. Daniel] Phys Sci Inc, Andover, MA 01810 USA. [Iyer, Arun K.; Amiji, Mansoor] Northeastern Univ, Sch Pharm, Boston, MA 02115 USA. [Pitman, Martha] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Iftimia, N (reprint author), Phys Sci Inc, 20 New England Business Ctr, Andover, MA 01810 USA. EM iftimia@psicorp.com RI Amiji, Mansoor/A-4365-2014 OI Amiji, Mansoor/0000-0001-6170-881X FU National Institutes of Health [5R41 CA 132256] FX This work was funded by the National Institutes of Health (Grant 5R41 CA 132256). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. NR 37 TC 18 Z9 19 U1 2 U2 7 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 JAN 1 PY 2012 VL 3 IS 1 BP 178 EP 191 PG 14 WC Biochemical Research Methods; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Biochemistry & Molecular Biology; Optics; Radiology, Nuclear Medicine & Medical Imaging GA 886WM UT WOS:000299884600016 PM 22254178 ER PT J AU Davis, BJ Horwitz, EM Lee, WR Crook, JM Stock, RG Merrick, GS Butler, WM Grimm, PD Stone, NN Potters, L Zietman, AL Zelefsky, MJ AF Davis, Brian J. Horwitz, Eric M. Lee, W. Robert Crook, Juanita M. Stock, Richard G. Merrick, Gregory S. Butler, Wayne M. Grimm, Peter D. Stone, Nelson N. Potters, Louis Zietman, Anthony L. Zelefsky, Michael J. TI American Brachytherapy Society consensus guidelines for transrectal ultrasound-guided permanent prostate brachytherapy SO BRACHYTHERAPY LA English DT Article DE Prostate cancer; Brachytherapy; Quality assurance; Safety; Dosimetry; Guideline; Standard; Interstitial; Radiation therapy; Radiotherapy ID EXTERNAL-BEAM RADIOTHERAPY; PUBIC ARCH INTERFERENCE; ACUTE URINARY RETENTION; VOLUME HISTOGRAM ANALYSIS; BODY-MASS INDEX; POSTIMPLANT DOSIMETRIC ANALYSIS; ANDROGEN DEPRIVATION THERAPY; QUALITY-OF-LIFE; INTERSTITIAL-BRACHYTHERAPY; SEED IMPLANTATION AB PURPOSE: To provide updated American Brachytherapy Society (ABS) guidelines for transrectal ultrasound-guided transperineal interstitial permanent prostate brachytherapy (PPB). METHODS AND MATERIALS: The ABS formed a committee of brachytherapists and researchers experienced in the clinical practice of PPB to formulate updated guidelines for this technique. Sources of input for these guidelines included prior published guidelines, clinical trials, published literature, and experience of the committee. The recommendations of the committee were reviewed and approved by the Board of Directors of the ABS. RESULTS: Patients with high probability of organ-confined disease or limited extraprostatic extension are considered appropriate candidates for PPB monotherapy. Low-risk patients may be treated with PPB alone without the need for supplemental external beam radiotherapy. High-risk patients should receive supplemental external beam radiotherapy if PPB is used. Intermediate-risk patients should be considered on an individual case basis. Intermediate-risk patients with favorable features may appropriately be treated with PPB monotherapy but results from confirmatory clinical trials are pending. Computed tomography based postimplant dosimetry performed within 60 days of the implant is considered essential for maintenance of a satisfactory quality assurance program. Postimplant computed tomography magnetic resonance image fusion is viewed as useful, but not mandatory. CONCLUSIONS: Updated guidelines for patient selection, workup, treatment, postimplant dosimetry, and followup are provided. These recommendations are intended to be advisory in nature with the ultimate responsibility for the care of the patients resting with the treating physicians. (C) 2012 Published by Elsevier Inc. on behalf of American Brachytherapy Society. All rights reserved. C1 [Davis, Brian J.] Mayo Clin, Dept Radiat Oncol, Rochester, MN 55905 USA. [Horwitz, Eric M.] Fox Chase Canc Ctr, Dept Radiat Oncol, Philadelphia, PA 19111 USA. [Lee, W. Robert] Duke Univ, Dept Radiat Oncol, Durham, NC USA. [Crook, Juanita M.] British Columbia Canc Agcy, Kelowna, BC, Canada. [Stock, Richard G.] Mt Sinai Med Ctr, Dept Radiat Oncol, New York, NY 10029 USA. [Merrick, Gregory S.; Butler, Wayne M.] Schiffler Canc Ctr, Wheeling, WV USA. [Merrick, Gregory S.; Butler, Wayne M.] Wheeling Jesuit Univ, Wheeling Hosp, Wheeling, WV USA. [Grimm, Peter D.] Prostate Canc Treatment Ctr, Seattle, WA USA. [Stone, Nelson N.] Mt Sinai Med Ctr, Dept Urol, New York, NY 10029 USA. [Potters, Louis] N Shore LIJ Hlth Syst, Dept Radiat Med, Oceanside, NY USA. [Zietman, Anthony L.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Zelefsky, Michael J.] Mem Sloan Kettering Canc Ctr, Dept Radiat Oncol, New York, NY 10021 USA. RP Davis, BJ (reprint author), Mayo Clin, Dept Radiat Oncol, 200 1st St SW, Rochester, MN 55905 USA. EM davis.brian@mayo.edu OI Davis, Brian/0000-0002-8288-1096; Potters, Louis/0000-0003-4922-2061 NR 168 TC 140 Z9 152 U1 2 U2 8 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1538-4721 J9 BRACHYTHERAPY JI Brachytherapy PD JAN-FEB PY 2012 VL 11 IS 1 SI SI BP 6 EP 19 DI 10.1016/j.brachy.2011.07.005 PG 14 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 886JS UT WOS:000299851300004 PM 22265434 ER PT J AU Viswanathan, AN Thomadsen, B AF Viswanathan, Akila N. Thomadsen, Bruce CA Amer Brachytherapy Soc TI American Brachytherapy Society consensus guidelines for locally advanced carcinoma of the cervix. Part I: General principles SO BRACHYTHERAPY LA English DT Article DE Cervical cancer; Brachytherapy; Guidelines ID MODULATED RADIATION-THERAPY; DOSE-RATE BRACHYTHERAPY; INTRACAVITARY GYNECOLOGIC BRACHYTHERAPY; POSITRON-EMISSION-TOMOGRAPHY; SQUAMOUS-CELL CARCINOMA; PARAAORTIC LYMPH-NODES; UTERINE CERVIX; CANCER BRACHYTHERAPY; CONCURRENT CHEMOTHERAPY; COMPUTED-TOMOGRAPHY AB PURPOSE: To develop brachytherapy recommendations covering aspects of pretreatment evaluation, treatment, and dosimetric issues for locally advanced cervical cancer. METHODS: Members of the American Brachytherapy Society (ABS) with expertise in cervical cancer brachytherapy formulated updated recommendations for locally advanced (Federation of Gynecology and Obstetrics Stages IB2-IVA) cervical cancer based on literature review and clinical experience. RESULTS: The ABS recommends the use of brachytherapy as a component of the definitive treatment of locally advanced cervical carcinoma. Precise applicator placement is necessary to maximize the probability of achieving local control without major side effects. The ABS recommends a cumulative delivered dose of approximately 80-90 Gy for definitive treatment. The close delivered to point A should be reported for all brachytherapy applications regardless of treatment-planning technique. The ABS also recommends adoption of the Groupe Europeen Curietherapie-European Society of Therapeutic Radiation Oncology (GEC-ESTRO) guidelines for contouring, image-based treatment planning, and dose reporting. Interstitial brachytherapy may be considered for a small proportion of patients whose disease cannot be adequately encompassed by intracavitary application. It should be performed by practitioners with special expertise in these procedures. CONCLUSIONS: Updated ABS recommendations are provided for brachytherapy for locally advanced cervical cancer. Practitioners and cooperative groups are encouraged to use these recommendations to formulate their clinical practices and to adopt dose-reporting policies that are critical for outcome analysis. (C) 2012 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved. C1 [Viswanathan, Akila N.] Brigham & Womens Hosp, Dept Radiat Oncol, Boston, MA 02115 USA. [Viswanathan, Akila N.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Thomadsen, Bruce] Univ Wisconsin, Madison, WI USA. RP Viswanathan, AN (reprint author), Brigham & Womens Hosp, Dept Radiat Oncol, 75 Francis St,ASB 1,L2, Boston, MA 02115 USA. EM abs@americanbrachytherapy.org RI Beriwal, Sushil/J-6404-2012; OI Kirisits, Christian/0000-0002-2815-8083 NR 99 TC 96 Z9 100 U1 1 U2 11 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1538-4721 J9 BRACHYTHERAPY JI Brachytherapy PD JAN-FEB PY 2012 VL 11 IS 1 SI SI BP 33 EP 46 DI 10.1016/j.brachy.2011.07.003 PG 14 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 886JS UT WOS:000299851300006 PM 22265436 ER PT J AU Viswanathan, AN Beriwal, S De Los Santos, JF Demanes, DJ Gaffney, D Hansen, J Jones, E Kirisits, C Thomadsen, B Erickson, B AF Viswanathan, Akila N. Beriwal, Sushil De Los Santos, Jennifer F. Demanes, D. Jeffrey Gaffney, David Hansen, Jorgen Jones, Ellen Kirisits, Christian Thomadsen, Bruce Erickson, Beth TI American Brachytherapy Society consensus guidelines for locally advanced carcinoma of the cervix. Part II: High-dose-rate brachytherapy SO BRACHYTHERAPY LA English DT Article DE Cervical cancer; Brachytherapy; High dose rate ID RATE INTRACAVITARY THERAPY; UTERINE CERVIX; RANDOMIZED-TRIAL; CANCER; PATTERNS; CARE; RADIOTHERAPY; RADIATION AB PURPOSE: This report presents an update to the American Brachytherapy Society (ABS) high-dose-rate (HDR) brachytherapy guidelines for locally advanced cervical cancer. METHODS: Members of the ABS with expertise in cervical cancer formulated updated guidelines for HDR brachytherapy using tandem and ring, ovoids, cylinder, or interstitial applicators for locally advanced cervical cancer. These guidelines were written based on medical evidence in the literature and input of clinical experts in gynecologic brachytherapy. RESULTS: The ABS affirms the essential curative role of tandem-based brachytherapy in the management of locally advanced cervical cancer. Proper applicator selection, insertion, and imaging are fundamental aspects of the procedure. Three-dimensional imaging with magnetic resonance or computed tomography or radiographic imaging may be used for treatment planning. Dosimetry must be performed after each insertion before treatment delivery. Applicator placement, dose specification, and dose fractionation must be documented, quality assurance measures must be performed, and follow-up information must be obtained. A variety of dose/fractionation schedules and methods for integrating brachytherapy with external-beam radiation exist. The recommended tumor close in 2-Gray (Gy) per fraction radiobiologic equivalence (normalized therapy dose) is 80-90 Gy, depending on tumor size at the time of brachytherapy. Dose limits for normal tissues are discussed. CONCLUSION: These guidelines update those of 2000 and provide a comprehensive description of HDR cervical cancer brachytherapy in 2011. (C) 2012 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved. C1 [Viswanathan, Akila N.; Hansen, Jorgen] Brigham & Womens Hosp, Dept Radiat Oncol, Dana Farber Canc Inst, Boston, MA 02115 USA. [Viswanathan, Akila N.; Hansen, Jorgen] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Beriwal, Sushil] Univ Pittsburgh, Sch Med, Dept Radiat Oncol, Pittsburgh, PA USA. [De Los Santos, Jennifer F.] Univ Alabama Birmingham, Dept Radiat Oncol, Birmingham, AL USA. [Demanes, D. Jeffrey] Univ Calif Los Angeles, David Geffen Sch Med, Dept Radiat Oncol, Los Angeles, CA 90095 USA. [Gaffney, David] Univ Utah, Dept Radiat Oncol, Huntsman Canc Ctr, Salt Lake City, UT USA. [Jones, Ellen] Univ N Carolina, Dept Radiat Oncol, Chapel Hill, NC USA. [Kirisits, Christian] Med Univ Vienna, Dept Radiotherapy, Vienna, Austria. [Thomadsen, Bruce] Univ Wisconsin, Dept Med Phys, Madison, WI 53706 USA. [Thomadsen, Bruce] Univ Wisconsin, Dept Human Oncol, Madison, WI USA. [Erickson, Beth] Med Coll Wisconsin, Dept Radiat Oncol, Milwaukee, WI 53226 USA. RP Viswanathan, AN (reprint author), Brigham & Womens Hosp, Dept Radiat Oncol, Dana Farber Canc Inst, 75 Francis St,ASB 1,L2, Boston, MA 02115 USA. EM abs@americanbrachytherapy.org RI Beriwal, Sushil/J-6404-2012; OI Kirisits, Christian/0000-0002-2815-8083 FU NCI NIH HHS [K07 CA117979] NR 25 TC 93 Z9 96 U1 3 U2 9 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1538-4721 J9 BRACHYTHERAPY JI Brachytherapy PD JAN-FEB PY 2012 VL 11 IS 1 SI SI BP 47 EP 52 DI 10.1016/j.brachy.2011.07.002 PG 6 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 886JS UT WOS:000299851300007 PM 22265437 ER PT J AU Lee, LJ Das, IJ Higgins, SA Jhingran, A Small, W Thomadsen, B Viswanathan, AN Wolfson, A Eifel, P AF Lee, Larissa J. Das, Indra J. Higgins, Susan A. Jhingran, Anuja Small, William, Jr. Thomadsen, Bruce Viswanathan, Akila N. Wolfson, Aaron Eifel, Patricia TI American Brachytherapy Society consensus guidelines for locally advanced carcinoma of the cervix. Part III: Low-dose-rate and pulsed-dose-rate brachytherapy SO BRACHYTHERAPY LA English DT Article DE Cervical cancer; Brachytherapy; Low-dose-rate; Pulsed-dose-rate; Guidelines ID SQUAMOUS-CELL CARCINOMA; CT-COMPATIBLE VERSION; UTERINE CERVIX; RADIATION-THERAPY; WORKING GROUP; INTRACAVITARY BRACHYTHERAPY; CANCER BRACHYTHERAPY; VOLUME PARAMETERS; QUALITY-ASSURANCE; PDR BRACHYTHERAPY AB PURPOSE: To develop a guideline for quality practice of low-dose-rate (LDR) and pulsed-dose-rate (PDR) brachytherapy for locally advanced cervical cancer. METHODS: Members of the American Brachytherapy Society (ABS) with expertise in cervical cancer brachytherapy formulated updated guidelines for LDR and PDR brachytherapy for locally advanced (International Federation of Gynecology and Obstetrics [FIGO] Stages IB2-IVA) cervical cancer based on literature review and clinical experience. RESULTS: The ABS strongly recommends the use of brachytherapy as a component of the definitive treatment of locally advanced cervical carcinoma. Precise applicator placement is necessary to maximize the probability of achieving local control without major side effects. The ABS recommends a cumulative delivered dose of approximately 80-90 Gy for definitive treatment. Dosimetry must be performed after each insertion before treatment delivery. The dose delivered to point A should be reported for all intracavitary brachytherapy applications regardless of treatment planning technique. The ABS also recommends adoption of the Groupe Europeen de Curietherapie-European Society for Therapeutic Radiology and Oncology guidelines for contouring, image-based treatment planning and dose reporting. Interstitial brachytherapy may be considered for a small proportion of patients whose disease cannot be adequately encompassed by intracavitary application and should be performed by practitioners with special expertise in these procedures. Quality management measures must be performed, and follow-up information should also be obtained. CONCLUSIONS: Updated ABS guidelines are provided for LDR and PDR brachytherapy for locally advanced cervical cancer. Practitioners and cooperative groups are encouraged to use these guidelines to formulate their clinical practices and to adopt dose-reporting policies that are critical for outcome analysis. (C) 2012 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved. C1 [Lee, Larissa J.; Viswanathan, Akila N.] Brigham & Womens Hosp, Dept Radiat Oncol, Boston, MA 02115 USA. [Lee, Larissa J.; Viswanathan, Akila N.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Das, Indra J.] Indiana Univ Sch Med, Dept Radiat Oncol, Indianapolis, IN USA. [Higgins, Susan A.] Yale Univ, Sch Med, Dept Therapeut Radiol, New Haven, CT 06510 USA. [Jhingran, Anuja; Eifel, Patricia] Univ Texas MD Anderson Canc Ctr, Dept Radiat Oncol, Houston, TX 77030 USA. [Small, William, Jr.] Northwestern Univ, Dept Radiat Oncol, Robert H Lurie Comprehens Canc Ctr, Chicago, IL 60611 USA. [Thomadsen, Bruce] Univ Wisconsin, Dept Med Phys, Madison, WI 53706 USA. [Wolfson, Aaron] Univ Miami, Miller Sch Med, Dept Radiat Oncol, Miami, FL 33136 USA. RP Viswanathan, AN (reprint author), Brigham & Womens Hosp, Dept Radiat Oncol, 75 Francis St,ASB1,L2, Boston, MA 02115 USA. EM aviswanathan@lroc.harvard.edu NR 34 TC 25 Z9 25 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1538-4721 J9 BRACHYTHERAPY JI Brachytherapy PD JAN-FEB PY 2012 VL 11 IS 1 SI SI BP 53 EP 57 DI 10.1016/j.brachy.2011.07.001 PG 5 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 886JS UT WOS:000299851300008 PM 22265438 ER PT J AU Beriwal, S Demanes, DJ Erickson, B Jones, E De Los Santos, JF Cormack, RA Yashar, C Rownd, JJ Viswanathan, AN AF Beriwal, Sushil Demanes, D. Jeffrey Erickson, Beth Jones, Ellen De Los Santos, Jennifer F. Cormack, Robert A. Yashar, Catheryn Rownd, Jason J. Viswanathan, Akila N. TI American Brachytherapy Society consensus guidelines for interstitial brachytherapy for vaginal cancer SO BRACHYTHERAPY LA English DT Article DE HDR; Vagina; Interstitial ID DOSE-RATE BRACHYTHERAPY; RATE INTRACAVITARY BRACHYTHERAPY; RECURRENT ENDOMETRIAL CANCER; EXTERNAL-BEAM RADIOTHERAPY; SQUAMOUS-CELL CARCINOMA; GYNECOLOGIC MALIGNANCIES; MAGNETIC-RESONANCE; RADIATION-THERAPY; CERVICAL-CANCER; PROGNOSTIC-FACTORS AB PURPOSE: To present recommendations for the use of interstitial brachytherapy in patients with vaginal cancer or recurrent endometrial cancer in the vagina. METHODS: A panel of members of the American Brachytherapy Society reviewed the literature, supplemented that with their clinical experience, and formulated recommendations for interstitial brachytherapy for primary or recurrent cancers in the vagina. RESULTS: Patients with bulky disease (approximately > 0.5 cm thick) should be considered for treatment with interstitial brachytherapy. The American Brachytherapy Society reports specific recommendations for techniques, target volume definition, and dose-fractionation schemes. Three-dimensional treatment planning is recommended with CT scan and/or MRI. The treatment plan should be optimized to conform to the clinical target volume and should reduce the dose to critical organs, including the rectum, bladder, urethra, and sigmoid colon. Suggested doses in combination with external beam radiation therapy and summated equivalent doses in 2 Gy fractions are tabulated. CONCLUSION: Recommendations are made for interstitial brachytherapy for vaginal cancer and recurrent disease in the vagina. Practitioners and cooperative groups are encouraged to use these recommendations to formulate treatment and dose-reporting policies. Such a process will result in meaningful outcome comparisons, promote technical advances, and lead to appropriate utilization of these techniques. (C) 2012 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved. C1 [Beriwal, Sushil] Univ Pittsburgh, Dept Radiat Oncol, Inst Canc, Pittsburgh, PA USA. [Demanes, D. Jeffrey] Univ Calif Los Angeles, Dept Radiat Oncol, Calif Endocurietherapy Program, Los Angeles, CA 90024 USA. [Erickson, Beth; Rownd, Jason J.] Med Coll Wisconsin, Dept Radiat Oncol, Milwaukee, WI 53226 USA. [Jones, Ellen] Univ N Carolina, Dept Radiat Oncol, Chapel Hill, NC USA. [De Los Santos, Jennifer F.] Univ Alabama Birmingham, Dept Radiat Oncol, Birmingham, AL USA. [Cormack, Robert A.] Harvard Univ, Dept Radiat Oncol, Sch Med, Boston, MA USA. [Yashar, Catheryn] Univ Calif San Diego, Dept Radiat Oncol, Moores Canc Ctr, La Jolla, CA 92093 USA. [Viswanathan, Akila N.] Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. RP Beriwal, S (reprint author), UPMC, Magee Womens Hosp, 300 Halket St, Pittsburgh, PA 15213 USA. EM beriwals@upmc.edu RI Beriwal, Sushil/J-6404-2012; OI Cormack, Robert/0000-0001-5553-9984 NR 73 TC 36 Z9 37 U1 2 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1538-4721 J9 BRACHYTHERAPY JI Brachytherapy PD JAN-FEB PY 2012 VL 11 IS 1 SI SI BP 68 EP 75 DI 10.1016/j.brachy.2011.06.008 PG 8 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 886JS UT WOS:000299851300010 PM 22265440 ER PT J AU Badalian-Very, G Vergilio, JA Degar, BA Rodriguez-Galindo, C Rollins, BJ AF Badalian-Very, Gayane Vergilio, Jo-Anne Degar, Barbara A. Rodriguez-Galindo, Carlos Rollins, Barrett J. TI Recent advances in the understanding of Langerhans cell histiocytosis SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Review DE histiocytosis; BRAF; neoplasia; dendritic cell ID CHEMOKINE RECEPTOR EXPRESSION; LA MICROSCOPIE ELECTRONIQUE; MATURE DENDRITIC CELLS; BONE-MARROW; STEADY-STATE; MONOCLONAL-ANTIBODIES; ADHESION MOLECULES; BRAF MUTATIONS; E-CADHERIN; IN-VIVO AB Langerhans cell histiocytosis (LCH) is a proliferative disease of cells that share phenotypic characteristics with the primary antigen presenting cells of the epidermis. Its clinical manifestations are highly variable, extending from very benign forms to a disseminated, aggressive disease that causes significant mortality. Although many of the fundamental pathogenetic features of LCH have been enigmatic, recent advances have led to a much clearer understanding of the disease. In particular, careful molecular analyses of mouse models and human LCH samples suggest that LCHs cell of origin may not be the epidermal LC itself but a myeloid-derived precursor. Advanced genomic technologies have revealed the presence of activating, somatic BRAF mutations in the majority of patient specimens. Together, these observations have produced a new picture of LCH as a myeloid neoplasm. These advances are likely to have profound implications for the use of targeted therapeutics in LCH. C1 [Badalian-Very, Gayane; Rollins, Barrett J.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. [Vergilio, Jo-Anne] Childrens Hosp, Dept Pathol, Boston, MA 02115 USA. [Degar, Barbara A.; Rodriguez-Galindo, Carlos] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02215 USA. [Badalian-Very, Gayane; Rollins, Barrett J.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med, Boston, MA 02115 USA. [Degar, Barbara A.; Rodriguez-Galindo, Carlos] Harvard Univ, Childrens Hosp Boston, Sch Med, Dept Med, Boston, MA 02115 USA. [Badalian-Very, Gayane; Vergilio, Jo-Anne; Degar, Barbara A.; Rodriguez-Galindo, Carlos; Rollins, Barrett J.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Badalian-Very, Gayane; Vergilio, Jo-Anne; Degar, Barbara A.; Rodriguez-Galindo, Carlos; Rollins, Barrett J.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. RP Rollins, BJ (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 450 Brookline Ave, Boston, MA 02215 USA. EM barrett_rollins@dfci.harvard.edu FU Histiocytosis Association of America; Team Ippolittle/Deloitte of the Boston Marathon Jimmy Fund Walk; PHS [AI050225] FX The authors acknowledge support from the Histiocytosis Association of America, Team Ippolittle/Deloitte of the Boston Marathon Jimmy Fund Walk and PHS grant AI050225. The authors also appreciate the insights and ideas of Dr. Mark D. Fleming. NR 103 TC 39 Z9 44 U1 0 U2 6 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD JAN PY 2012 VL 156 IS 2 BP 163 EP 172 DI 10.1111/j.1365-2141.2011.08915.x PG 10 WC Hematology SC Hematology GA 867UJ UT WOS:000298480000002 PM 22017623 ER PT J AU Ngo, DA Aygun, B Akinsheye, I Hankins, JS Bhan, I Luo, HY Steinberg, MH Chui, DHK AF Ngo, Duyen A. Aygun, Banu Akinsheye, Idowu Hankins, Jane S. Bhan, Ishir Luo, Hong Y. Steinberg, Martin H. Chui, David H. K. TI Fetal haemoglobin levels and haematological characteristics of compound heterozygotes for haemoglobin S and deletional hereditary persistence of fetal haemoglobin SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Article DE fetal haemoglobin; sickle cell; hereditary persistence of fetal haemoglobin ID SICKLE-CELL-ANEMIA; MOLECULAR-BASIS; GAMMA-CHAIN; F-CELLS; HB-F; DISEASE; ERYTHROCYTES; ADULT AB Compound heterozygotes for sickle haemoglobin (HbS) and hereditary persistence of fetal haemoglobin (HPFH) have high fetal haemoglobin (HbF) levels but few, if any, sickle cell disease-related complications. We studied 30 cases of HbS-HPFH (types 1 and 2), confirmed by molecular analysis, and report the haematological features and change in HbF levels over time. These results were compared to those of patients with sickle cell anaemia or HbS-beta degrees thalassaemia, including a subgroup of patients carrying the XmnI polymorphism, known to be associated with elevated HbF. Among the HbS-HPFH patients, HbF level was 5090% during infancy and declined steeply within the first few years of life, stabilizing between ages 3 and 5 years, at approximately 30%. Mean HbF of individuals age 5 or older was 31 +/- 3%, average haemoglobin concentration was 130 +/- 10 g/l and average mean corpuscular volume (MCV) was 75 +/- 4 fl. Univariate and multivariate regression analyses significantly associated HbF with age, haemoglobin concentration, and MCV (P < 0.001). There was a strong inverse association between HbF and age (r = -0.9, P < 0.001). Despite having a much higher HbF level, patients with HbS-HPFH have a similar age-related pattern of HbF decline and associations as patients with sickle cell anaemia or HbS-beta degrees thalassaemia. C1 [Ngo, Duyen A.; Akinsheye, Idowu; Luo, Hong Y.; Steinberg, Martin H.; Chui, David H. K.] Boston Univ, Med Ctr, Dept Med, Boston, MA 02118 USA. [Aygun, Banu; Hankins, Jane S.] St Jude Childrens Hosp, Dept Hematol, Memphis, TN 38105 USA. [Bhan, Ishir] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Ngo, DA (reprint author), Boston Univ, Med Ctr, Dept Med, 820 Harrison Ave,FGH 1025, Boston, MA 02118 USA. EM duyen.ngo@bmc.org OI Ngo, Duyen/0000-0001-6125-7756; Steinberg, Martin/0000-0001-8800-8020 FU American Lebanese Syrian Associated Charities; [U54 HL070819-07]; [U54 HL 70819]; [R01 HL068970]; [R01 DK069646] FX This work was supported by: U54 HL070819-07 (DAN), U54 HL 70819 (MHS), R01 HL068970 (MHS), R01 DK069646 (DHKC), and in part by the American Lebanese Syrian Associated Charities (BA, JSH). NR 18 TC 20 Z9 20 U1 0 U2 8 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD JAN PY 2012 VL 156 IS 2 BP 259 EP 264 DI 10.1111/j.1365-2141.2011.08916.x PG 6 WC Hematology SC Hematology GA 867UJ UT WOS:000298480000012 PM 22017641 ER PT J AU Roberts, NJ Jiao, YC Yu, J Kopelovich, L Petersen, GM Bondy, ML Gallinger, S Schwartz, AG Syngal, S Cote, ML Axilbund, J Schulick, R Ali, SZ Eshleman, JR Velculescu, VE Goggins, M Vogelstein, B Papadopoulos, N Hruban, RH Kinzler, KW Klein, AP AF Roberts, Nicholas J. Jiao, Yuchen Yu, Jun Kopelovich, Levy Petersen, Gloria M. Bondy, Melissa L. Gallinger, Steven Schwartz, Ann G. Syngal, Sapna Cote, Michele L. Axilbund, Jennifer Schulick, Richard Ali, Syed Z. Eshleman, James R. Velculescu, Victor E. Goggins, Michael Vogelstein, Bert Papadopoulos, Nickolas Hruban, Ralph H. Kinzler, Kenneth W. Klein, Alison P. TI ATM Mutations in Patients with Hereditary Pancreatic Cancer SO CANCER DISCOVERY LA English DT Article ID ATAXIA-TELANGIECTASIA; BREAST-CANCER; GENE; IDENTIFICATION; HETEROZYGOTES; PHENOTYPES; FAMILIES; TUMORS; ONSET AB Pancreatic cancers are the fourth most-common cause of cancer-related deaths in the Western world, with >200,000 cases reported in 2010. Although up to 10% of these cases occur in familial patterns, the hereditary basis for predisposition in the vast majority of affected families is unknown. We used next-generation sequencing, including whole-genome and whole-exome analyses, and identified heterozygous, constitutional, ataxia telangiectasia mutated (ATM) gene mutations in 2 kindreds with familial pancreatic cancer. Mutations segregated with disease in both kindreds and tumor analysis demonstrated LOH of the wild-type allele. By using sequence analysis of an additional 166 familial pancreatic cancer probands, we identified 4 additional patients with deleterious mutations in the ATM gene, whereas we identified no deleterious mutations in 190 spouse controls (P = 0.046). When we considered only the mostly severely affected families with 3 or more pancreatic cancer cases, 4 deleterious mutations were found in 87 families (P = 0.009). Our results indicate that inherited ATM mutations play an important role in familial pancreatic cancer predisposition. SIGNIFICANCE : The genes responsible for the majority of cases of familial pancreatic ductal adenocarcinoma are unknown. We here identify ATM as a predisposition gene for pancreatic ductal adenocarcinoma. Our results have important implications for the management of patients in affected families and illustrate the power of genome-wide sequencing to identify the basis of familial cancer syndromes. Cancer Discovery; 2(1): 41-6. (C) 2011 AACR. C1 [Yu, Jun; Axilbund, Jennifer; Ali, Syed Z.; Eshleman, James R.; Goggins, Michael; Hruban, Ralph H.; Klein, Alison P.] Johns Hopkins Med Inst, Sol Goldman Pancreat Canc Res Ctr, Dept Pathol, Baltimore, MD 21231 USA. [Schulick, Richard] Johns Hopkins Med Inst, Sol Goldman Pancreat Canc Res Ctr, Dept Surg, Baltimore, MD 21231 USA. [Goggins, Michael; Hruban, Ralph H.; Klein, Alison P.] Johns Hopkins Med Inst, Sol Goldman Pancreat Canc Res Ctr, Dept Oncol, Baltimore, MD 21231 USA. [Yu, Jun; Goggins, Michael] Johns Hopkins Med Inst, Sol Goldman Pancreat Canc Res Ctr, Dept Med, Baltimore, MD 21231 USA. [Roberts, Nicholas J.; Jiao, Yuchen; Velculescu, Victor E.; Vogelstein, Bert; Papadopoulos, Nickolas; Kinzler, Kenneth W.] Johns Hopkins Kimmel Canc Ctr, Ludwig Ctr Canc Genet, Baltimore, MD USA. [Roberts, Nicholas J.; Jiao, Yuchen; Velculescu, Victor E.; Vogelstein, Bert; Papadopoulos, Nickolas; Kinzler, Kenneth W.] Johns Hopkins Kimmel Canc Ctr, Howard Hughes Med Inst, Baltimore, MD USA. [Klein, Alison P.] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. [Kopelovich, Levy] NCI, Canc Prevent Div, Bethesda, MD 20892 USA. [Petersen, Gloria M.] Mayo Clin, Div Epidemiol, Rochester, MN USA. [Bondy, Melissa L.] Baylor Coll Med, Dan L Duncan Canc Ctr, Houston, TX 77030 USA. [Gallinger, Steven] Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Univ Hlth Network, Hepatobiliary Pancreat Surg Oncol Program, Toronto, ON M5G 1X5, Canada. [Schwartz, Ann G.; Cote, Michele L.] Wayne State Univ, Sch Med, Karmanos Canc Inst, Detroit, MI USA. [Syngal, Sapna] Dana Farber Canc Inst, Div Populat Sci, Boston, MA 02115 USA. [Syngal, Sapna] Brigham & Womens Hosp, Div Gastroenterol, Boston, MA 02115 USA. RP Klein, AP (reprint author), Johns Hopkins Med Inst, Sol Goldman Pancreat Canc Res Ctr, Dept Pathol, 303 CRB2,1550 Orleans St, Baltimore, MD 21231 USA. EM rhruban@jhmi.edu; kinzlke@jhmi.edu; aklein1@jhmi.edu RI Papadopoulos, Nickolas/K-7272-2012; Gallinger, Steven/E-4575-2013 FU Lustgarten Foundation for Pancreatic Cancer Research; Virginia and D. K. Ludwig Fund for Cancer Research; Sol Goldman Pancreatic Cancer Research Center NIH [CA62924, CA057345, CA123483, CA121113, RO1CA97075]; Michael Rolfe Pancreatic Cancer Foundation; Stand Up To Cancer Dream Team; Entertainment Industry Foundation [SU2C-AACR-DT0509]; Stringer Foundation; Joseph L. Rabinowitz Fund for Pancreatic Cancer Research; Karp Family; H.H. & M. Metals, Inc.; Fund for Cancer Research; NCI [N01-PC-35145, NO1-CN-43302] FX This work was supported by the Lustgarten Foundation for Pancreatic Cancer Research; The Virginia and D. K. Ludwig Fund for Cancer Research; Sol Goldman Pancreatic Cancer Research Center NIH grants CA62924, CA057345, CA123483, CA121113, and RO1CA97075; the Michael Rolfe Pancreatic Cancer Foundation; V. E. Velculescu, R. H. Hruban, and K. W. Kinzler are supported by a Stand Up To Cancer Dream Team Translational Research Grant, a Program of the Entertainment Industry Foundation (SU2C-AACR-DT0509); The Stringer Foundation; The Joseph L. Rabinowitz Fund for Pancreatic Cancer Research; the family and friends of Dick Knox and Cliff Minor; The Karp Family; H.H. & M. Metals, Inc. Fund for Cancer Research; and NCI contracts N01-PC-35145 and NO1-CN-43302. NR 29 TC 136 Z9 139 U1 0 U2 15 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 2159-8274 J9 CANCER DISCOV JI Cancer Discov. PD JAN PY 2012 VL 2 IS 1 BP 41 EP 46 DI 10.1158/2159-8290.CD-11-0194 PG 6 WC Oncology SC Oncology GA 883LR UT WOS:000299636100030 PM 22585167 ER PT J AU Weigert, O Kopp, N Lane, AA Yoda, A Dahlberg, SE Neuberg, D Bahar, AY Chapuy, B Kutok, JL Longtine, JA Kuo, FC Haley, T Salois, M Sullivan, TJ Fisher, DC Fox, EA Rodig, SJ Antin, JH Weinstock, DM AF Weigert, Oliver Kopp, Nadja Lane, Andrew A. Yoda, Akinori Dahlberg, Suzanne E. Neuberg, Donna Bahar, Anita Y. Chapuy, Bjoern Kutok, Jeffery L. Longtine, Janina A. Kuo, Frank C. Haley, Terry Salois, Maura Sullivan, Timothy J. Fisher, David C. Fox, Edward A. Rodig, Scott J. Antin, Joseph H. Weinstock, David M. TI Molecular Ontogeny of Donor-Derived Follicular Lymphomas Occurring after Hematopoietic Cell Transplantation SO CANCER DISCOVERY LA English DT Article ID NON-HODGKINS-LYMPHOMAS; SOMATIC MUTATIONS; LEUKEMIA; INDIVIDUALS; SURVIVAL; DISEASE; PROTEIN; GENOME; DIFFER; ARID1A AB The relative timing of genetic alterations that contribute to follicular lymphoma remains unknown. We analyzed a donor-recipient pair who both developed grade 2/3A follicular lymphoma 7 years after allogeneic transplantation and donor lymphocyte infusions. Both patients harbored identical BCL2/IGH rearrangements also present in 1 in 2,000 cells in the donor lymphocyte infusion, and the same V(D)J rearrangement, which underwent somatic hypermutation both before and after clonal divergence. Exome sequencing of both follicular lymphomas identified 15 shared mutations, of which 14 (including alterations in EP300 and KLHL6) were recovered from the donor lymphocyte infusion by ultra-deep sequencing (average read coverage, 361,723), indicating acquisition at least 7 years before clinical presentation. Six additional mutations were present in only one follicular lymphoma and not the donor lymphocyte infusion, including an ARID1A premature stop, indicating later acquisition during clonal divergence. Thus, ultrasensitive sequencing can map clonal evolution within rare subpopulations during human lymphomagenesis in vivo. SIGNIFICANCE: For the first time, we define the molecular ontogeny of follicular lymphoma during clonal evolution in vivo. By using ultrasensitive mutation detection, we mapped the time-course of somatic alterations after passage of a malignant ancestor by hematopoietic cell transplantation. Cancer Discovery; 2(1); 47-55. (C) 2011 AACR. C1 [Weigert, Oliver; Kopp, Nadja; Lane, Andrew A.; Yoda, Akinori; Chapuy, Bjoern; Fisher, David C.; Antin, Joseph H.; Weinstock, David M.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. [Dahlberg, Suzanne E.; Neuberg, Donna] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02215 USA. [Haley, Terry; Salois, Maura; Sullivan, Timothy J.; Fox, Edward A.] Dana Farber Canc Inst, Dept Microarray Core, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA USA. [Bahar, Anita Y.; Longtine, Janina A.; Kuo, Frank C.; Rodig, Scott J.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Kutok, Jeffery L.] Infin Pharmaceut, Cambridge, MA USA. RP Weinstock, DM (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 450 Brookline Ave,Dana 510B, Boston, MA 02215 USA. EM dweinstock@partners.org FU Deutsche Forschungsgemeinschaft [WE 4679]; Jock and Bunny Adams Education and Research Endowment; Stand Up To Cancer Innovative Research; Entertainment Industry Foundation [SU2C-AACR-IRG0409]; American Cancer Society [RSG-10-181-01-RMC]; Stellato Fund FX O. Weigert is supported by the Deutsche Forschungsgemeinschaft (WE 4679). J.H. Antin is supported by the Jock and Bunny Adams Education and Research Endowment. D. M. Weinstock is supported by a Stand Up To Cancer Innovative Research Grant, a Program of the Entertainment Industry Foundation (SU2C-AACR-IRG0409); an American Cancer Society Research Scholar Grant (RSG-10-181-01-RMC); and the Stellato Fund. NR 27 TC 29 Z9 29 U1 1 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 2159-8274 J9 CANCER DISCOV JI Cancer Discov. PD JAN PY 2012 VL 2 IS 1 BP 47 EP 55 DI 10.1158/2159-8290.CD-11-0208 PG 9 WC Oncology SC Oncology GA 883LR UT WOS:000299636100031 PM 22585168 ER PT J AU Wagle, N Berger, MF Davis, MJ Blumenstiel, B DeFelice, M Pochanard, P Ducar, M Van Hummelen, P MacConaill, LE Hahn, WC Meyerson, M Gabriel, SB Garraway, LA AF Wagle, Nikhil Berger, Michael F. Davis, Matthew J. Blumenstiel, Brendan DeFelice, Matthew Pochanard, Panisa Ducar, Matthew Van Hummelen, Paul MacConaill, Laura E. Hahn, William C. Meyerson, Matthew Gabriel, Stacey B. Garraway, Levi A. TI High-Throughput Detection of Actionable Genomic Alterations in Clinical Tumor Samples by Targeted, Massively Parallel Sequencing SO CANCER DISCOVERY LA English DT Article ID BREAST-CANCER; COLORECTAL-CANCER; BRAF MUTATIONS; PI3K PATHWAY; TAMOXIFEN RESISTANCE; HYBRID SELECTION; POOR-PROGNOSIS; GENE-MUTATIONS; PLASMA DNA; AMPLIFICATION AB Knowledge of "actionable" somatic genomic alterations present in each tumor (e.g., point mutations, small insertions/deletions, and copy-number alterations that direct therapeutic options) should facilitate individualized approaches to cancer treatment. However, clinical implementation of systematic genomic profiling has rarely been achieved beyond limited numbers of oncogene point mutations. To address this challenge, we utilized a targeted, massively parallel sequencing approach to detect tumor genomic alterations in formalin-fixed, paraffin-embedded (FFPE) tumor samples. Nearly 400-fold mean sequence coverage was achieved, and single-nucleotide sequence variants, small insertions/deletions, and chromosomal copy-number alterations were detected simultaneously with high accuracy compared with other methods in clinical use. Putatively actionable genomic alterations, including those that predict sensitivity or resistance to established and experimental therapies, were detected in each tumor sample tested. Thus, targeted deep sequencing of clinical tumor material may enable mutation-driven clinical trials and, ultimately, "personalized" cancer treatment. SIGNIFICANCE : Despite the rapid proliferation of targeted therapeutic agents, systematic methods to profile clinically relevant tumor genomic alterations remain underdeveloped. We describe a sequencing-based approach to identifying genomic alterations in FFPE tumor samples. These studies affirm the feasibility and clinical utility of targeted sequencing in the oncology arena and provide a foundation for genomics-based stratification of cancer patients. Cancer Discovery; 2(1); 82-93. (C) 2011 AACR. C1 [Wagle, Nikhil; Pochanard, Panisa; Hahn, William C.; Meyerson, Matthew; Garraway, Levi A.] Harvard Univ, Dana Farber Canc Inst, Dept Med Oncol, Sch Med, Boston, MA 02215 USA. [Wagle, Nikhil; Davis, Matthew J.; Ducar, Matthew; Van Hummelen, Paul; MacConaill, Laura E.; Hahn, William C.; Meyerson, Matthew; Garraway, Levi A.] Harvard Univ, Dana Farber Canc Inst, Ctr Canc Genome Discovery, Sch Med, Boston, MA 02215 USA. [Wagle, Nikhil; Berger, Michael F.; Blumenstiel, Brendan; DeFelice, Matthew; Hahn, William C.; Meyerson, Matthew; Gabriel, Stacey B.; Garraway, Levi A.] Broad Inst MIT & Harvard, Cambridge, MA USA. RP Garraway, LA (reprint author), Harvard Univ, Dana Farber Canc Inst, Dept Med Oncol, Sch Med, 450 Brookline Ave,D1542, Boston, MA 02215 USA. EM levi_garraway@dfci.harvard.edu RI Meyerson, Matthew/E-7123-2012; Davis, Matt/F-9045-2012 FU NIH [DP2OD002750]; National Cancer Institute [R33CA126674, U24CA143867]; Snyder Medical Foundation; Starr Cancer Consortium; Novartis FX This work was supported by the NIH Director's New Innovator Award DP2OD002750 (L.A. Garraway), the National Cancer Institute R33CA126674 (L.A. Garraway), the National Cancer Institute U24CA143867 (M. Meyerson), the Snyder Medical Foundation (W.C. Hahn), and the Starr Cancer Consortium (M.F. Berger, L.A. Garraway).; Research support: Novartis (W.C. Hahn, M. Meyerson, L.A. Garraway). NR 56 TC 220 Z9 222 U1 1 U2 24 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 2159-8274 J9 CANCER DISCOV JI Cancer Discov. PD JAN PY 2012 VL 2 IS 1 BP 82 EP 93 DI 10.1158/2159-8290.CD-11-0184 PG 12 WC Oncology SC Oncology GA 883LR UT WOS:000299636100034 PM 22585170 ER PT J AU Hoge, EA Worthington, JJ Nagurney, JT Chang, YC Kay, EB Feterowski, CM Katzman, AR Goetz, JM Rosasco, ML Lasko, NB Zusman, RM Pollack, MH Orr, SP Pitman, RK AF Hoge, Elizabeth A. Worthington, John J. Nagurney, John T. Chang, Yuchiao Kay, Elaine B. Feterowski, Christine M. Katzman, Anna R. Goetz, Jared M. Rosasco, Maria L. Lasko, Natasha B. Zusman, Randall M. Pollack, Mark H. Orr, Scott P. Pitman, Roger K. TI Effect of Acute Posttrauma Propranolol on PTSD Outcome and Physiological Responses During Script-Driven Imagery SO CNS NEUROSCIENCE & THERAPEUTICS LA English DT Article DE Post-traumatic stress disorder; Propranolol; PTSD prevention script-driven imagery; Trauma ID ACUTE STRESS DISORDER; MEMORY; TRAUMA AB Introduction: Animal and human research suggests that the development of posttraumatic stress disorder (PTSD) may involve the overconsolidation of memories of a traumatic experience. Previous studies have attempted to use pharmaceutical agents, especially the beta-adrenergic blocker propranolol, to reduce this overconsolidation. Aims: In this randomized, placebo-controlled study of the efficacy of propranolol in reducing the development of PTSD, we optimized dosages and conducted both psychophysiological and clinical assessments 1 and 3 months after the traumatic event. Forty-one emergency department patients who had experienced a qualifying acute psychological trauma were randomized to receive up to 240 mg/day of propranolol or placebo for 19 days. At 4 and 12 weeks post-trauma, PTSD symptoms were assessed. One week later, participants engaged in script-driven imagery of their traumatic event while psychophysiological responses were measured. Results: Physiological reactivity during script-driven traumatic imagery, severity of PTSD symptoms, and the rate of the PTSD diagnostic outcome were not significantly different between the two groups. However, post hoc subgroup analyses showed that in participants with high drug adherence, at the 5-week posttrauma assessment, physiological reactivity was significantly lower during script-driven imagery in the propranolol than in the placebo subjects. Conclusions: The physiological results provide some limited support for a model of PTSD in which a traumatic conditioned response is reduced by posttrauma propranolol. However, the clinical results from this study do not support the preventive use of propranolol in the acute aftermath of a traumatic event. C1 [Hoge, Elizabeth A.; Worthington, John J.; Kay, Elaine B.; Feterowski, Christine M.; Katzman, Anna R.; Goetz, Jared M.; Rosasco, Maria L.; Lasko, Natasha B.; Pollack, Mark H.; Orr, Scott P.; Pitman, Roger K.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Hoge, Elizabeth A.; Worthington, John J.; Nagurney, John T.; Chang, Yuchiao; Kay, Elaine B.; Feterowski, Christine M.; Katzman, Anna R.; Goetz, Jared M.; Rosasco, Maria L.; Lasko, Natasha B.; Zusman, Randall M.; Pollack, Mark H.; Orr, Scott P.; Pitman, Roger K.] Harvard Univ, Sch Med, Boston, MA USA. [Nagurney, John T.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. [Chang, Yuchiao; Zusman, Randall M.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Orr, Scott P.] VA Med Ctr, Res Serv, Manchester, NH USA. RP Hoge, EA (reprint author), Massachusetts Gen Hosp, Dept Psychiat, 1 Bowdoin Sq,6th Flr, Boston, MA 02114 USA. EM ehoge@partners.org RI Hoge, Elizabeth/H-5879-2012 OI Hoge, Elizabeth/0000-0002-5513-2292 FU NIMH [MH068603]; Sepracor; Forest Pharmaceuticals, Sepracor; U.S. Army [W81XWH-07-1-0440, W81XWH-08-2-0126] FX This study was funded by NIMH grant #MH068603 to R.K.P.; Hoge: Research Funding: Sepracor; Worthington: Research Funding: Forest Pharmaceuticals, Sepracor; Nagurney: none; Chang: none; Kay: none; Feterowski: none; Katzman: none; Goetz: none; Rosasco: none; Zusman: Speakers bureau/consultant: Bristol-Myers Squibb, Sanofi-Aventis, Novartis, Pfizer, Forest, Daichii Sankyo, Eli Lilly, Astra Zeneca and Nicox pharmaceutical companies; Pollack: Advisory Boards and Consultation: Brain Cells, Eli Lilly, Medavante, Labopharm, Mindsite, Sepracor, Targia Pharmaceuticals. Pfizer; Research Grants: Bristol Myers Squibb, Forest Laboratories, GlaxoSmithKline, Eli Lilly, NCCAM, NIDA, NIMH, Sepracor; CME Supported Activities: Astra-Zeneca, Sepracor, Pfizer; Equity: Medavante, Mensante Corporation, Mindsite, Targia Pharmaceuticals; Royalty/patent: SIGH-A, SAFER interviews; Orr: none; Pitman: Recipient of two current U.S. Army grants: #W81XWH-07-1-0440 and #W81XWH-08-2-0126; recipient of a small annual royalty for a book chapter on legal issues in PTSD; part-time private practice of forensic psychiatry. NR 19 TC 58 Z9 59 U1 4 U2 21 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1755-5930 J9 CNS NEUROSCI THER JI CNS Neurosci. Ther. PY 2012 VL 18 IS 1 BP 21 EP 27 DI 10.1111/j.1755-5949.2010.00227.x PG 7 WC Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA 881FR UT WOS:000299468500004 PM 22070357 ER PT J AU Joshi, G Biederman, J Wozniak, J Doyle, R Hammerness, P Galdo, M Sullivan, N Williams, C Brethel, K Woodworth, KY Mick, E AF Joshi, Gagan Biederman, Joseph Wozniak, Janet Doyle, Robert Hammerness, Paul Galdo, Maribel Sullivan, Nora Williams, Courtney Brethel, Kristin Woodworth, K. Yvonne Mick, Eric TI Response to Second Generation Antipsychotics in Youth with Comorbid Bipolar Disorder and Autism Spectrum Disorder SO CNS NEUROSCIENCE & THERAPEUTICS LA English DT Article DE Autism spectrum disorder (ASD); bipolar disorder (BPD); comorbid ID PERVASIVE DEVELOPMENTAL DISORDERS; MANIA RATING-SCALE; DOUBLE-BLIND; OPEN-LABEL; INFANTILE-AUTISM; AGE-CHILDREN; RISPERIDONE; PLACEBO; ADOLESCENTS; TRIAL AB Objective: To assess the impact of comorbid autism spectrum disorders (ASD) on the response to second-generation antipsychotics (SGA) in pediatric bipolar disorder (BPD). Methods: Secondary analysis of identically designed 8-week open-label trials of SGA monotherapy (risperidone, olanzapine, quetiapine, ziprasidone, or aripiprazole) in youth with BPD. Results: Of the 151 BPD subjects 15% (n= 23) met criteria for comorbid ASD. There were no differences in the rate of antimanic response (YMRS change =30% or CGI-Improvement =2: 65% vs. 69%; P= 0.7) in the presence of comorbid ASD. Conclusion: No difference observed in the rate of antimanic response or tolerability to SGA monotherapy in the presence of ASD comorbidity. C1 [Joshi, Gagan] Massachusetts Gen Hosp, Pediat Psychopharmacol Res Program, Pediat Psychopharmacol Res Dept, Boston, MA 02114 USA. [Joshi, Gagan; Biederman, Joseph; Wozniak, Janet; Doyle, Robert; Hammerness, Paul; Mick, Eric] Harvard Univ, Sch Med, Boston, MA USA. RP Joshi, G (reprint author), Massachusetts Gen Hosp, Pediat Psychopharmacol Res Program, Pediat Psychopharmacol Res Dept, 55 Fruit St, Boston, MA 02114 USA. EM Joshi.Gagan@mgh.harvard.edu OI Mick, Eric/0000-0001-8505-8145; Brethel-Haurwitz, Kristin/0000-0003-0429-4598 FU AstraZeneca; Bristol-Myers Squibb; Janssen LP; Pfizer Inc; Stanley Medical Research Institute; Norma Fine Pediatric Psychopharmacology; MGH Pediatric Psychopharmacology Council; American Academy of Child and Adolescent Psychiatry; McNeil Pediatrics; SynerMed Communications; Glaxo Smith Kline; Abbott; Cephalon; Eli Lilly Co.; Johnson Johnson; McNeil; Merck; New River; Novartis; Organon; Otsuka; Takeda; Pfizer; Shire Pharmaceuticals; Elminda; Janssen; Next Wave Pharmaceuticals; Shire; MGH Psychiatry Academy; Fundacion Dr. Manuel Camelo A.C.; Ortho-McNeil Janssen; Eli Lilly; Elminda Ltd; Ortho-McNeil Janssen Scientific Affairs FX This work was supported by grants from industry (AstraZeneca, Bristol-Myers Squibb, Janssen LP, Pfizer Inc) and the Stanley Medical Research Institute to Dr Biederman. We also wish to acknowledge the generous support from the Norma Fine Pediatric Psychopharmacology Fellowship Fund and members of the MGH Pediatric Psychopharmacology Council.; Dr. Gagan Joshi has received the Ethel DuPontWarren Fellowship Award 2005-2006 and the Pilot Research Award from the American Academy of Child and Adolescent Psychiatry 2005. He is a reviewer and member of the National Institute of Mental Health Editorial Board. He has received CME sponsored support from McNeil Pediatrics (CME sponsored by SynerMed Communications). He was supported by Shire as a member of the national advisory board for the year 2009. Dr. Joshi has received research support from Bristol Myers Squibb and Glaxo Smith Kline (Site PI for Multi-centered Trials). Dr. Joshi has received research support as a co-investigator for clinical trials sponsored by Abbott, Bristol Myers Squibb, Cephalon, Eli Lilly & Co., Johnson & Johnson, McNeil, Merck, New River, Novartis, Organon, Otsuka, Takeda, Pfizer, and Shire Pharmaceuticals.; Dr. Joseph Biederman is currently receiving research support from the following sources: Elminda, Janssen, McNeil, Next Wave Pharmaceuticals, and Shire. In 2011, Dr. Biederman gave a single unpaid talk for Juste Pharmaceutical Spain, and received honoraria from the MGH Psychiatry Academy for a tuition-funded CME course. In 2010, Dr. Biederman received a speaker's fee from Fundacion Dr. Manuel Camelo A.C., provided single consultations for Shionogi Pharma Inc. and Cipher Pharmaceuticals Inc., and received honoraria from the MGH Psychiatry Academy for a tuition-funded CME course.; Dr. Paul Hammerness has participated in CME activities/professional talks supported by Ortho-McNeil Janssen and Shire and served on the advisory board for Shire. He has participated, as an investigator/principal investigator, in research studies funded by the following pharmaceutical companies/companies: Cephalon, Eli Lilly, Elminda Ltd, GlaxoSmithKline, Johnson & Johnson, McNeil, Merck, New River, Novartis, Ortho-McNeil Janssen, Pfizer, Shire, Takeda. Dr. Hammerness has also received honoraria from commercial entities supporting the MGH Psychiatry Academy, www.mghcme.org.; Dr. Eric Mick has received research support from Ortho-McNeil Janssen Scientific Affairs, Pfizer, Shire Pharmaceuticals, and has been an advisory board member for Shire Pharmaceuticals. NR 37 TC 9 Z9 10 U1 1 U2 9 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1755-5930 J9 CNS NEUROSCI THER JI CNS Neurosci. Ther. PY 2012 VL 18 IS 1 BP 28 EP 33 DI 10.1111/j.1755-5949.2010.00219.x PG 6 WC Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA 881FR UT WOS:000299468500005 PM 21114638 ER PT J AU Hammerness, P Biederman, J Petty, C Henin, A Moore, CM AF Hammerness, Paul Biederman, Joseph Petty, Carter Henin, Aude Moore, Constance M. TI Brain Biochemical Effects of Methylphenidate Treatment Using Proton Magnetic Spectroscopy in Youth with Attention-Deficit Hyperactivity Disorder: A Controlled Pilot Study SO CNS NEUROSCIENCE & THERAPEUTICS LA English DT Article DE ADHD; Methylphenidate; Spectroscopy ID H-1-MAGNETIC RESONANCE SPECTROSCOPY; DEFICIT/HYPERACTIVITY DISORDER; BIPOLAR DISORDER; CHILDREN; ADOLESCENTS; ADHD; METAANALYSIS; LCMODEL; SPECTRA; MODEL AB Introduction: This study conducted spectroscopic analyses using proton (1H) Magnetic Resonance Spectroscopy (at 4 Tesla) in a sample of adolescents with Attention Deficit Hyperactivity Disorder (ADHD), before and after treatment with extended release methylphenidate (OROS MPH), as compared to a sample of healthy comparators. Aims: The main aim of this study is to use 1H MRS to measure differences in brain biochemistry between adolescents with and without ADHD, and to assess changes in cerebral biochemistry, before and after stimulant treatment in ADHD youth. Results: Subjects with ADHD were medically healthy adolescents treated in an open label fashion with OROS MPH (mean dose: 54 mg/day; 0.90 mg/kg/day). Subjects with ADHD were scanned before and after OROS MPH treatment. Healthy comparators were scanned once. Magnetic resonance (MR) spectroscopy studies were performed on a 4.0 T Varian Unity/Inova MR scanner; proton spectra were acquired from the Anterior Cingulate Cortex (ACC). Data were analyzed using MANOVA and repeated measurement ANOVA. Higher metabolite ratios (Glutamate/myo-inositol, Glutamine/myo-inositol, Glutamate + Glutamine/myo-inositol) were observed in the ACC in untreated ADHD subjects as compared to controls, and to treated ADHD youth; these group differences did not reach the a priori threshold for statistical significance. Conclusions: These preliminary findings suggest the presence of glutamatergic abnormalities in adolescents with ADHD, which may normalize with MPH treatment. Larger sample, controlled studies are needed to confirm these preliminary findings. C1 [Hammerness, Paul; Biederman, Joseph; Petty, Carter; Henin, Aude] Massachusetts Gen Hosp, Clin & Res Program Pediat Psychopharmacol, Cambridge, MA 02138 USA. [Hammerness, Paul; Biederman, Joseph; Petty, Carter; Henin, Aude] Harvard Univ, Sch Med, Boston, MA USA. [Moore, Constance M.] Univ Massachusetts, Ctr Comparat Neuro Imaging, Sch Med, Cambridge, MA USA. RP Hammerness, P (reprint author), Massachusetts Gen Hosp, Clin & Res Program Pediat Psychopharmacol, 185 Alewife Brook Pkwy,Suite 2000, Cambridge, MA 02138 USA. EM phammerness@partners.org FU Pediatric Psychopharmacology Council; McNeil Pharmaceuticals; Eli Lilly; Forest; McNeil; Shire; Elminda Ltd.; Alza; AstraZeneca; Bristol Myers Squibb; Eli Lilly and Co.; Janssen Pharmaceuticals Inc.; Merck; Organon; Otsuka; NIMH; NICHD; Fundacion Areces; Medice Pharmaceuticals; Spanish Child Psychiatry Association; Abbott; Celltech; Cephalon; Esai; Glaxo; Gliatech; Janssen; NARSAD; NIDA; New River; Novartis; Noven; Neurosearch; Pfizer; Pharmacia; Prechter Foundation; Stanley Foundation; UCB Pharma, Inc.; Wyeth; Oxford University Press; McNeil Pediatrics; Forest Laboratories Inc.; Sanofi aventis; Bristol-Myers Squibb FX We thank Timothy Wilens, M.D., and J. Eric Jensen, Ph.D., for their help with this project. This work was supported in part by the Pediatric Psychopharmacology Council Fund and by McNeil Pharmaceuticals (ClinicalTrials.gov; NCT00181714).; In the past 2 years, Dr. Hammerness has received research funds or participated in CME activities/professional talks supported by the following pharmaceutical companies: Eli Lilly, Forest, McNeil, Shire. Dr. Hammerness has also received research funds from Elminda Ltd. and has served on the advisory board for Shire. In the past 2 years, Dr. Hammerness has participated, as an investigator, in research studies funded by the following pharmaceutical companies: Cephalon, Eli Lilly, Glaxo-SmithKline, Johnson & Johnson, McNeil, Ortho-McNeil Janssen, Merck, New River, Novartis, Organon, Pfizer, Shire, Takeda. Dr. Hammerness has also received honoraria from Reed Medical Education (a logistics collaborator for the MGH Psychiatry Academy). Commercial entities supporting the MGH Psychiatry Academy are listed on the Academy's website, www.mghcme.org.; Dr. Joseph Biederman is currently receiving research support from the following sources: Alza, AstraZeneca, Bristol Myers Squibb, Eli Lilly and Co., Janssen Pharmaceuticals Inc., McNeil, Merck, Organon, Otsuka, Shire, NIMH, and NICHD. In 2009, Dr. Joseph Biederman received a speaker's fee from the following sources: Fundacion Areces, Medice Pharmaceuticals, and the Spanish Child Psychiatry Association. In previous years, Dr. Joseph Biederman received research support, consultation fees, or speaker's fees for/from the following additional sources: Abbott, AstraZeneca, Celltech, Cephalon, Eli Lilly and Co., Esai, Forest, Glaxo, Gliatech, Janssen, McNeil, NARSAD, NIDA, New River, Novartis, Noven, Neurosearch, Pfizer, Pharmacia, The Prechter Foundation, Shire, The Stanley Foundation, UCB Pharma, Inc. and Wyeth.; Dr. Henin has received honoraria from Shire, Abbott Laboratories, and AACAP. She receives royalties from Oxford University Press. She has also received honoraria from Reed Medical Education (a company working as a logistics collaborator for the MGH Psychiatry Academy). The education programs conducted by the MGH Psychiatry Academy were, in part, supported though Independent Medical Education grants from pharmaceutical companies, including AstraZeneca, Lilly, McNeil Pediatrics, Shire, Forest Laboratories Inc., Sanofi aventis, Janssen, Bristol-Myers Squibb, and Pfizer. NR 29 TC 20 Z9 20 U1 3 U2 9 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1755-5930 J9 CNS NEUROSCI THER JI CNS Neurosci. Ther. PY 2012 VL 18 IS 1 BP 34 EP 40 DI 10.1111/j.1755-5949.2010.00226.x PG 7 WC Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA 881FR UT WOS:000299468500006 PM 21143432 ER PT J AU McMurrich, SL Johnson, SL Peckham, AD AF McMurrich, Stephanie L. Johnson, Sheri L. Peckham, Andrew D. TI Situational Rumination: A Method for Minimizing Retrospective Reporting Bias SO CNS NEUROSCIENCE & THERAPEUTICS LA English DT Letter ID DEPRESSION; MEMORY; CRITICISM; PRAISE C1 [McMurrich, Stephanie L.; Peckham, Andrew D.] Massachusetts Gen Hosp, Bipolar Clin & Res Program, Boston, MA 02114 USA. [Johnson, Sheri L.] Univ Calif Berkeley, Dept Clin Sci, Berkeley, CA 94720 USA. RP McMurrich, SL (reprint author), Massachusetts Gen Hosp, Bipolar Clin & Res Program, 50 Staniford St,Suite 580, Boston, MA 02114 USA. EM smcmurrich@partners.org RI johnson, sheri/D-8712-2014 OI johnson, sheri/0000-0002-9945-4816 NR 10 TC 0 Z9 0 U1 1 U2 5 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1755-5930 J9 CNS NEUROSCI THER JI CNS Neurosci. Ther. PY 2012 VL 18 IS 1 BP 87 EP 88 DI 10.1111/j.1755-5949.2011.00279.x PG 2 WC Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA 881FR UT WOS:000299468500012 PM 22280159 ER PT J AU Hinton, DE AF Hinton, Devon E. TI MULTICULTURAL CHALLENGES IN THE DELIVERY OF ANXIETY TREATMENT SO DEPRESSION AND ANXIETY LA English DT Editorial Material ID POSTTRAUMATIC-STRESS-DISORDER; TREATMENT-RESISTANT PTSD; PRIMARY-CARE PATIENTS; CAMBODIAN REFUGEES; PANIC-ATTACKS; DEPRESSION; SENSITIVITY; OUTCOMES; THERAPY; NERVIOS C1 Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. RP Hinton, DE (reprint author), Massachusetts Gen Hosp, Dept Psychiat, 15 Parkman St,WACC 812, Boston, MA 02114 USA. EM devon_hinton@hms.hardvard.edu NR 25 TC 4 Z9 4 U1 0 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1091-4269 J9 DEPRESS ANXIETY JI Depress. Anxiety PD JAN PY 2012 VL 29 IS 1 BP 1 EP 3 DI 10.1002/da.20889 PG 3 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA 886DY UT WOS:000299833400001 PM 22307921 ER PT J AU Janes, AC Smoller, JW David, SP Frederick, BD Haddad, S Basu, A Fava, M Evins, AE Kaufman, MJ AF Janes, Amy C. Smoller, Jordan W. David, Sean P. Frederick, Blaise deB. Haddad, Stephen Basu, Aditi Fava, Maurizio Evins, A. Eden Kaufman, Marc J. TI Association between CHRNA5 genetic variation at rs16969968 and brain reactivity to smoking images in nicotine dependent women SO DRUG AND ALCOHOL DEPENDENCE LA English DT Article DE Tobacco smoking; fMRI; CHRNA5; Nicotine dependence; Dorsal striatum ID ACETYLCHOLINE-RECEPTORS; CIGARETTE-SMOKING; CUES; MEMORY; FMRI; ACTIVATION; WITHDRAWAL; ADDICTION; ALPHA-5; PHARMACOLOGY AB Background: Tobacco smoking is the leading preventable cause of death in the developed world. Identifying risk factors for smoking may lead to more effective treatments. Genome wide association studies revealed a relationship between development of nicotine dependence and a single-nucleotide polymorphism (SNP, rs16969968) of the nicotine acetylcholine receptor (nAChR) alpha-5 subunit gene (CHRNA5). The relationship between this SNP and other factors contributing to smoking behavior such as smoking cue reactivity is unclear. Methods: We assessed the role of rs16969968 on brain functional MRI (fMRI) reactivity to smoking cues by studying nicotine dependent women with the nicotine dependence 'risk' allele (A allele, N = 14) and without the 'risk' allele (G/G smokers, N = 10). Nicotine dependence severity, as assessed with the Fagerstrom test for nicotine dependence, smoking pack-years, and expired carbon monoxide levels, were equivalent in these groups. Results: We observed a group difference in fMRI reactivity; women without the A allele (G/G smokers) showed greater fMRI reactivity to smoking images in brain areas related to memory and habitual behavior such as the hippocampus and dorsal striatum. Conclusions: Our finding suggests that nicotine-dependent smokers lacking the rs16969968 A allele are more likely to recall smoking-related memories and engage in habitual responding to smoking cues than A allele smokers. Although more studies are necessary to determine the mechanism underlying and significance of this cue reactivity difference, these data suggest that smokers may develop and remain nicotine dependent due to different factors including genetics and cue reactivity. This finding may have implications for personalizing smoking treatment. (C) 2011 Elsevier Ireland Ltd. All rights reserved. C1 [Janes, Amy C.; Frederick, Blaise deB.; Kaufman, Marc J.] Harvard Univ, McLean Hosp, Sch Med, Brain Imaging Ctr, Belmont, MA 02478 USA. [Smoller, Jordan W.; Haddad, Stephen; Basu, Aditi; Fava, Maurizio; Evins, A. Eden] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [David, Sean P.] Ctr Educ & Res Family & Community Med & PharmGKB, Stanford, CA USA. [David, Sean P.] SRI Int, Menlo Pk, CA 94025 USA. RP Janes, AC (reprint author), Harvard Univ, McLean Hosp, Sch Med, Brain Imaging Ctr, 115 Mill St, Belmont, MA 02478 USA. EM ajanes@mclean.harvard.edu RI Frederick, Blaise/G-6098-2012; Janes, Amy/A-5322-2013; OI Frederick, Blaise/0000-0001-5832-5279; Janes, Amy/0000-0002-3749-5006; David, Sean/0000-0002-4922-2603 FU National Institute on Drug Abuse [U01DA019378, R01DA022276, R01DA014674, R01DA09448, K02DA017324, T32DA015036]; Counter-Drug Technology Assessment Center (CTAC), an office within the Office of National Drug Control Policy (ONDCP) via Army Contracting Agency [BK39-03-C-0075]; GlaxoSmithKline; Pfizer; Abbott Laboratories; Alkermes; Aspect Medical Systems; Astra-Zeneca; BioResearch; Brain Cells, Inc.; Bristol-Myers Squibb Company; Cephalon; Clinical Trial Solutions, LLC; Eli Lilly Company; Forest Pharmaceuticals Inc.; Ganeden; J & J Pharmaceuticals; Lichtwer Pharma GmbH; Lorex Pharmaceuticals; NARSAD; NCCAM; NIDA; NIMH; Novartis; Organon Inc.; PamLab, LLC; Pfizer Inc.; Pharmavite; Roche; Sanofi-Aventis; Shire; Solvay Pharmaceuticals, Inc.; Synthelabo; Wyeth-Ayerst Laboratories; Organon; Varian Inc.; [R21DA027331]; [R24GM61374] FX This research was supported in part by National Institute on Drug Abuse grants U01DA019378, R01DA022276, R01DA014674, R01DA09448, K02DA017324, T32DA015036, by funding from the Counter-Drug Technology Assessment Center (CTAC), an office within the Office of National Drug Control Policy (ONDCP) via Army Contracting Agency contract BK39-03-C-0075, and by research support from GlaxoSmithKline. Personal support to SPD from R21DA027331 and R24GM61374. No funding sources played a role in the study design, collection, analysis and interpretation of the data, in the writing of the report; or the decision to submit the paper for publication.; No disclosures: ACJ, JWS, SPD, BBF, SH, AB. AEE: Research Product Support from Pfizer, and Speaker Honoraria from Reed Medical Education. MF: Research support: Abbott Laboratories, Alkermes, Aspect Medical Systems, Astra-Zeneca, BioResearch, Brain Cells, Inc., Bristol-Myers Squibb Company, Cephalon, Clinical Trial Solutions, LLC, Eli Lilly & Company, Forest Pharmaceuticals Inc., Ganeden, GlaxoSmithKline, J & J Pharmaceuticals, Lichtwer Pharma GmbH, Lorex Pharmaceuticals, NARSAD, NCCAM, NIDA, NIMH, Novartis, Organon Inc., PamLab, LLC, Pfizer Inc., Pharmavite, Roche, Sanofi-Aventis, Shire, Solvay Pharmaceuticals, Inc., Synthelabo, Wyeth-Ayerst Laboratories.; MJK: Research support: GSK, Organon, Varian Inc., Advisory/consulting: Amgen, Novartis. NR 45 TC 20 Z9 20 U1 1 U2 5 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0376-8716 J9 DRUG ALCOHOL DEPEN JI Drug Alcohol Depend. PD JAN 1 PY 2012 VL 120 IS 1-3 BP 7 EP 13 DI 10.1016/j.drugalcdep.2011.06.009 PG 7 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA 881PY UT WOS:000299499800002 PM 21764527 ER PT J AU Anderson, AL Li, SH Biswas, K McSherry, F Holmes, T Iturriaga, E Kahn, R Chiang, N Beresford, T Campbell, J Haning, W Mawhinney, J McCann, M Rawson, R Stock, C Weis, D Yu, E Elkashef, AM AF Anderson, Ann L. Li, Shou-Hua Biswas, Kousick McSherry, Frances Holmes, Tyson Iturriaga, Erin Kahn, Roberta Chiang, Nora Beresford, Thomas Campbell, Jan Haning, William Mawhinney, Joseph McCann, Michael Rawson, Richard Stock, Christopher Weis, Dennis Yu, Elmer Elkashef, Ahmed M. TI Modafinil for the treatment of methamphetamine dependence SO DRUG AND ALCOHOL DEPENDENCE LA English DT Article DE Methamphetamine; Substance-related disorders; Drug therapy; Modafinil; Medication adherence; Attention Deficit Hyperactivity Disorders ID PLACEBO-CONTROLLED TRIAL; ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; DOUBLE-BLIND; INDUCED WAKEFULNESS; COCAINE DEPENDENCE AB Aim: Modafinil was tested for efficacy in decreasing use in methamphetamine-dependent participants, compared to placebo. Methods: This was a randomized, double-blind, placebo-controlled study, with 12 weeks of treatment and a 4-week follow-up. Eight outpatient substance abuse treatment clinics participated in the study. There were 210 treatment-seekers randomized, who all had a DSM-IV diagnosis of methamphetamine dependence; 68 participants to placebo, 72 to modafinil 200 mg, and 70 to modafinil 400 mg, taken once daily on awakening. Participants came to the clinic three times per week for assessments, urine drug screens, and group psychotherapy. The primary outcome measure was a methamphetamine non-use week, which required all the week's qualitative urine drug screens to be negative for methamphetamine. Results: Regression analysis showed no significant difference between either modafinil group (200 or 400 mg) or placebo in change in weekly percentage having a methamphetamine non-use week over the 12-week treatment period (p=0.53). Similarly, a number of secondary outcomes did not show significant effects of modafinil. However, an ad-hoc analysis of medication compliance, by urinalysis for modafinil and its metabolite, did find a significant difference in maximum duration of abstinence (23 days vs. 10 days, p=0.003), between those having the top quartile of compliance (> 85% of urines were positive for modafinil, N=36), and the lower three quartiles of modafinil 200 and 400 mg groups (N=106). Conclusions: Although these data suggest that modafinil, plus group behavioral therapy, was not effective for decreasing methamphetamine use, the study is probably inconclusive because of inadequate compliance with taking medication. Published by Elsevier Ireland Ltd. C1 [Anderson, Ann L.] Natl Inst Drug Abuse, DPMC, Div Pharmacotherapies & Med Consequences Drug Abu, NIH, Bethesda, MD 20892 USA. [Biswas, Kousick; McSherry, Frances] VA Maryland Healthcare Ctr, Coop Studies Program, Perry Point, MD USA. [Holmes, Tyson] Stanford Univ, Sch Med, Dept Psychiat & Behav Sci, Stanford, CA 94305 USA. [Beresford, Thomas] VA Med Ctr, Psychiat Serv, Denver, CO USA. [Campbell, Jan] Univ Kansas, Med Ctr, Kansas City, KS 66103 USA. [Haning, William] Univ Hawaii, John A Burns Sch Med, Honolulu, HI 96822 USA. [Mawhinney, Joseph] S Bay Treatment Ctr, San Diego, CA USA. [McCann, Michael] Matrix Inst Addict, Los Angeles, CA USA. [Rawson, Richard] UCLA Integrated Subst Abuse Program, Los Angeles, CA USA. [Stock, Christopher] VA Salt Lake City Healthcare Syst, Salt Lake City, UT USA. [Weis, Dennis] Iowa Lutheran Hosp, Des Moines, IA USA. [Yu, Elmer] Philadelphia VA Med Ctr, Philadelphia, PA USA. RP Anderson, AL (reprint author), Natl Inst Drug Abuse, DPMC, Div Pharmacotherapies & Med Consequences Drug Abu, NIH, 6001 Execut Blvd,Rm 4149, Bethesda, MD 20892 USA. EM aa135m@nih.gov FU NIDA [Y1-DA-4006-01] FX Funding for this study was provided by NIDA Contract # Y1-DA-4006-01. The National Institute on Drug Abuse-NIH had a major role in study design, in the analysis and interpretation of data, and in the writing and submission of this manuscript for publication. NR 28 TC 44 Z9 45 U1 1 U2 11 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0376-8716 J9 DRUG ALCOHOL DEPEN JI Drug Alcohol Depend. PD JAN 1 PY 2012 VL 120 IS 1-3 BP 135 EP 141 DI 10.1016/j.drugalcdep.2011.07.007 PG 7 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA 881PY UT WOS:000299499800019 PM 21840138 ER PT J AU van Eeghen, AM Chu-Shore, CJ Pulsifer, MB Camposano, SE Thiele, EA AF van Eeghen, Agnies M. Chu-Shore, Catherine J. Pulsifer, Margaret B. Camposano, Susana E. Thiele, Elizabeth A. TI Cognitive and adaptive development of patients with tuberous sclerosis complex: A retrospective, longitudinal investigation SO EPILEPSY & BEHAVIOR LA English DT Article DE Tuberous sclerosis complex; Epilepsy; Cognition; Intelligence Quotient; Adaptive behavior; Development; Neurosurgery; Antiepileptic drugs; Interictal epileptiform discharges; Genetics ID EPILEPSY SURGERY; INFANTILE SPASMS; CHILDREN; TSC1; MUTATION; BEHAVIOR; INTELLIGENCE; IMPAIRMENT; CHILDHOOD; STABILITY AB Objective: The aim of the work described here was to systematically analyze the developmental trajectory of patients with tuberous sclerosis complex (TSC). Methods: A retrospective longitudinal chart review was performed, selecting patients who received multiple neuropsychological assessments. Intellectual/Developmental Quotients, Adaptive Behavior Composite scores, and clinical data were collected. On available EEGs, interictal epileptiform discharges were counted. Results: Sixty-six (18%) patients with TSC received multiple cognitive and adaptive development assessments. The mean intelligence of this study group remained relatively stable, albeit variable. Significant decline in adaptive functioning was observed, associated with lower age at seizure onset. Patients who underwent neurosurgery prior to baseline testing showed cognitive improvement. Developmental declines were significantly associated with increased numbers of antiepileptic drugs, with a trend toward association with mutation type and interictal epileptiform discharges. Conclusion: This study suggests that the developmental course of patients with TSC may be altered by epilepsy comorbidity and neurosurgery, underlining the need for early and effective interventions in this population. (C) 2011 Elsevier Inc. All rights reserved. C1 [van Eeghen, Agnies M.; Chu-Shore, Catherine J.; Camposano, Susana E.; Thiele, Elizabeth A.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [van Eeghen, Agnies M.] Erasmus MC, Expertise Ctr Neurodev Disorders, ENCORE, Rotterdam, Netherlands. [Pulsifer, Margaret B.] Massachusetts Gen Hosp, Dept Psychiat, Psychol Assessment Ctr, Boston, MA 02114 USA. RP Thiele, EA (reprint author), Carol & James Herscot Ctr Tuberous Sclerosis, Pediat Epilepsy Serv, 175 Cambridge St,Suite 340, Boston, MA 02114 USA. EM ethiele@partners.org FU Herscot Center for Tuberous Sclerosis Complex; NIH/NINDS [P01 NS024279] FX This study was sponsored by the Herscot Center for Tuberous Sclerosis Complex and by NIH/NINDS P01 NS024279. We thank Brian Healy of the Biostatistics Center of Massachusetts General Hospital for his assistance with statistical analysis. NR 37 TC 8 Z9 8 U1 1 U2 7 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1525-5050 J9 EPILEPSY BEHAV JI Epilepsy Behav. PD JAN PY 2012 VL 23 IS 1 BP 10 EP 15 DI 10.1016/j.yebeh.2011.10.005 PG 6 WC Behavioral Sciences; Clinical Neurology; Psychiatry SC Behavioral Sciences; Neurosciences & Neurology; Psychiatry GA 883XO UT WOS:000299668400003 PM 22099526 ER PT J AU Baca, CB Vickrey, BG Vassar, SD Berg, AT AF Baca, Christine B. Vickrey, Barbara G. Vassar, Stefanie D. Berg, Anne T. TI Seizure recency and quality of life in adolescents with childhood-onset epilepsy SO EPILEPSY & BEHAVIOR LA English DT Article DE Epilepsy; Children and adolescents; Health-related quality of life; Seizure recency; Seizure remission; Parent-proxy reports ID TEMPORAL-LOBE EPILEPSY; LONG-TERM PROGNOSIS; CHILDREN; HEALTH; SURGERY; IMPACT; OUTCOMES; SYMPTOMS; ANXIETY; ADULTS AB Health-related quality of life (HRQOL) is associated with seizure recency among adults with epilepsy. In a prospective, community-based study of long-term outcomes of childhood-onset epilepsy, we evaluated whether worse HRQOL is associated with more recent seizures among children and adolescents with epilepsy. We used the Child Health Questionnaire (CHQ), a generic measure with child and parent-proxy versions, to measure HRQOL Among 277 children with epilepsy (CWE) assessed 9 years after diagnosis, parent-proxy reported but not child self-reported HRQOL was significantly worse for those having seizures in the prior year than for those who were seizure free >= 1 year across the majority of scales. There were no differences between CWE in remission for 1-5 years and those seizure free >= 5 years for child and parent-proxy reported HRQOL with the exception of the parent Emotional Impact scale, suggesting that HRQOL differences related to seizure recency level off after the initial year of remission. Published by Elsevier Inc. C1 [Baca, Christine B.; Vickrey, Barbara G.; Vassar, Stefanie D.] Univ Calif Los Angeles, Dept Neurol, Los Angeles, CA 90024 USA. [Baca, Christine B.; Vickrey, Barbara G.; Vassar, Stefanie D.] VA Greater Los Angeles Hlth Care Syst, Dept Neurol, Los Angeles, CA USA. [Berg, Anne T.] NW Childrens Mem Hosp, Epilepsy Ctr, Chicago, IL USA. RP Baca, CB (reprint author), UCLA Neurol, RNRC, C-247, Los Angeles, CA 90095 USA. EM cbower@mednet.ucla.edu FU National Institutes of Health (PI) [NINDS R37-NS31146] FX This work was supported by Grant NINDS R37-NS31146 from the National Institutes of Health (PI-Berg). NR 40 TC 10 Z9 10 U1 2 U2 6 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1525-5050 J9 EPILEPSY BEHAV JI Epilepsy Behav. PD JAN PY 2012 VL 23 IS 1 BP 47 EP 51 DI 10.1016/j.yebeh.2011.10.010 PG 5 WC Behavioral Sciences; Clinical Neurology; Psychiatry SC Behavioral Sciences; Neurosciences & Neurology; Psychiatry GA 883XO UT WOS:000299668400009 PM 22134098 ER PT J AU Si, L Kong, Y Xu, XW Flaherty, KT Sheng, X Cui, CL Chi, ZH Li, SM Mao, LL Guo, J AF Si, Lu Kong, Yan Xu, Xiaowei Flaherty, Keith T. Sheng, Xinan Cui, Chuanliang Chi, Zhihong Li, Siming Mao, Lili Guo, Jun TI Prevalence of BRAF V600E mutation in Chinese melanoma patients: Large scale analysis of BRAF and NRAS mutations in a 432-case cohort SO EUROPEAN JOURNAL OF CANCER LA English DT Article DE Melanoma; BRAF; NRAS; Mutation; Overall survival ID N-RAS MUTATIONS; HUMAN CUTANEOUS MELANOMA; MALIGNANT-MELANOMA; METASTATIC MELANOMA; TUMOR PROGRESSION; MELANOCYTIC NEVI; POINT MUTATIONS; RELEVANCE; LESIONS; CANCER AB Background: Mutations of NRAS and BRAF have been described in Caucasian melanomas. However, the status and the clinical significance of BRAF and NRAS mutations in the Asian population have not been investigated on a large scale. Methods: Melanoma samples (n = 432) were analysed for mutations in exons 11 and 15 of the BRAF gene, and exons 1 and 2 of the NRAS gene in genomic DNA by polymerase chain reaction (PCR) amplification and Sanger sequencing. Mutations of BRAF and NRAS genes were correlated to clinicopathologic features and prognosis of the patients. Results: The incidence of somatic mutations within the BRAF and NRAS genes was 25.5% (110/432) and 7.2% (31/432), respectively. Among the 110 patients with BRAF mutations, 98 patients (89.1%) had V600E mutations. Melanomas without chronic sun-induced damage (Non-CSD) were more likely (P < 0.01) to show BRAF mutations while NRAS mutation frequency was unbiased between melanoma subtypes. Patients with genetic mutations in BRAF (P < 0.01) or NRAS (P = 0.04) gene are more likely to have ulceration as compared to patients without BRAF or NRAS mutations, respectively. Both BRAF (P = 0.003) and NRAS mutations (P = 0.031) are inversely correlated to overall survival. Conclusions: BRAF mutation is frequent while mutations in NRAS gene are rare. The most prevalent BRAF mutation type is V600E. Patients with mutations in BRAF or NRAS gene are frequently present with ulceration, and mutation in BRAF or NRAS gene is indicator for poor prognosis. Our study may warrant a clinical trial of kinase inhibitors targeting BRAF V600E in Chinese and Asian melanoma patients. Crown Copyright (C) 2011 Published by Elsevier Ltd. All rights reserved. C1 [Si, Lu; Kong, Yan; Sheng, Xinan; Cui, Chuanliang; Chi, Zhihong; Li, Siming; Mao, Lili; Guo, Jun] Peking Univ, Canc Hosp & Inst, Dept Renal Canc & Melanoma, Minist Educ,Key Lab Carcinogenesis & Translat Res, Beijing 100142, Peoples R China. [Xu, Xiaowei] Univ Penn, Dept Pathol & Lab Med, Abramson Canc Ctr, Philadelphia, PA 19104 USA. [Xu, Xiaowei] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. RP Guo, J (reprint author), Peking Univ, Canc Hosp & Inst, Dept Renal Canc & Melanoma, Minist Educ,Key Lab Carcinogenesis & Translat Res, 52 Fucheng Rd, Beijing 100142, Peoples R China. EM guoj307@126.com FU Program for New Century Excellent Talents in University [985-2-085-113]; National Natural Science Foundation of China [30973483]; Novartis Oncology in China; Program for Beijing Medical Disciplines Leaders [2011-2-25]; Program for Beijing Science Topicis FX This work is supported by the Program for New Century Excellent Talents in University (985-2-085-113), National Natural Science Foundation of China (30973483), Novartis Oncology in China, Program for Beijing Medical Disciplines Leaders (2011-2-25) and Program for Beijing Science Topicis. We thank the staff in the Department of Pathology of our hospital for help in collection and pathological analysis of tissue samples. NR 40 TC 73 Z9 84 U1 0 U2 12 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0959-8049 EI 1879-0852 J9 EUR J CANCER JI Eur. J. Cancer PD JAN PY 2012 VL 48 IS 1 BP 94 EP 100 DI 10.1016/j.ejca.2011.06.056 PG 7 WC Oncology SC Oncology GA 886PL UT WOS:000299866200012 PM 21788131 ER PT J AU Strutt, AM Simpson, R Jankovic, J York, MK AF Strutt, A. M. Simpson, R. Jankovic, J. York, M. K. TI Changes in cognitive-emotional and physiological symptoms of depression following STN-DBS for the treatment of Parkinson's disease SO EUROPEAN JOURNAL OF NEUROLOGY LA English DT Article DE cognition; depression; emotion; motor symptoms; Parkinson's disease; subthalamic nucleus deep brain stimulation; treatment ID DEEP-BRAIN-STIMULATION; SUBTHALAMIC NUCLEUS STIMULATION; QUALITY-OF-LIFE; TRIAL; MOOD; METAANALYSIS; MULTICENTER; OUTCOMES; ANXIETY; SCALES AB Background and purpose: Subthalamic nucleus deep brain stimulation (STN-DBS) has been shown to have beneficial effects on the motor features of Parkinsons disease (PD), but its impact on non-motor symptoms, most notably mood, has not been fully explored. Methods: In the first study to independently compare the emotional-cognitive and somatic/ physiological symptoms of depression, we examined mood differences in 17 bilateral STN-DBS and 22 matched non-surgical PD patients at baseline and 6 months. Results: The STN-DBS group reported higher levels of depression at baseline with significant endorsement of physical symptomatology. Postoperatively, no significant between-group differences in physical symptoms of depression were found. In contrast, a significant group by time interaction for cognitive-emotional symptoms of depression was found, with the STN-DBS group reporting an increase in psychological symptoms of distress. The STN-DBS group also reported an increase in anxiety following surgery. The suicide rate of 5% found in our study is consistent with other postoperative studies in PD. The impact of changes in levodopa and psychotropic medication are also explored. Conclusions: Preliminary results suggest that the motor improvement often observed in patients with PD following bilateral STN-DBS may be partially offset by an increase in affective-cognitive symptoms of depression. C1 [Strutt, A. M.; Jankovic, J.; York, M. K.] Baylor Coll Med, Dept Neurol, Houston, TX 77030 USA. [Strutt, A. M.; Jankovic, J.; York, M. K.] Baylor Coll Med, Parkinsons Dis Movement Disorder Clin, Houston, TX 77030 USA. [Simpson, R.] Methodist Neurol Inst, Dept Neurosurg, Houston, TX USA. [York, M. K.] PADRECC, Michael E DeBakey Vet Affairs Med Ctr, Houston, TX USA. RP Strutt, AM (reprint author), 6550 Fannin,Smith 1801, Houston, TX 77030 USA. EM adrianam@bcm.edu FU NIH/NINDS [K23] FX Work funded by a NIH/NINDS K23 grant (PI: York) and supported with resources from the Michael E. DeBakey Veteran's Affairs Hospital, Houston, TX, USA. The authors thank Kara M. Rherer for her assistance with data management, the participants of this study and the National Parkinson's Foundation. NR 35 TC 19 Z9 19 U1 1 U2 9 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1351-5101 J9 EUR J NEUROL JI Eur. J. Neurol. PD JAN PY 2012 VL 19 IS 1 BP 121 EP 127 DI 10.1111/j.1468-1331.2011.03447.x PG 7 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 878JW UT WOS:000299254100021 PM 21668586 ER PT J AU Morris, BL Scott, CA Wilkin, TJ Sax, PE Gulick, RM Freedberg, KA Schackman, BR AF Morris, Bethany L. Scott, Callie A. Wilkin, Timothy J. Sax, Paul E. Gulick, Roy M. Freedberg, Kenneth A. Schackman, Bruce R. TI Cost-effectiveness of Adding an Agent That Improves Immune Responses to Initial Antiretroviral Therapy (ART) in HIV-Infected Patients: Guidance for Drug Development SO HIV CLINICAL TRIALS LA English DT Article DE ART-naive; HIV; immune-enhanced ID UNITED-STATES; OPPORTUNISTIC INFECTIONS; HIV-1-INFECTED PATIENTS; EFAVIRENZ; LOPINAVIR/RITONAVIR; EMTRICITABINE; COMBINATION; ZIDOVUDINE; LAMIVUDINE; MARAVIROC AB Purpose: Adding an immune-enhancing agent to initial antiretroviral therapy (ART) for HIV is a potential strategy to ensure that patients achieve optimal immune response. Method: Using a mathematical model of HIV disease and treatment, we evaluated the treatment benefits and cost-effectiveness of adding a hypothetical immune-enhancing agent to the initial 6 months of ART. We assumed that the additional agent would result in a higher CD4 increase that would provide clinical benefit. The additional cost ($1,900/month) was based on the cost of a drug currently under investigation for immune enhancement. Outcomes included projected life expectancy and cost-effectiveness in 2009 US dollars/quality-adjusted life year (QALY) with costs and QALYs discounted at 3% annually. Results: Compared to standard ART, immune-enhanced ART resulting in an additional 40 CD4 cell/mu L increase at 6 months yields a 2.4 month projected undiscounted life expectancy increase with a cost-effectiveness ratio of $107,600/QALY. Achieving a cost-effectiveness ratio <$100,000/QALY requires a >43 CD4 cell/mu L improvement, or >19 cells/mu L if immune-enhancing agent costs are halved. Conclusions: In addition to showing clinical efficacy, investigational immune enhancement agents need to increase CD4 counts more than has been previously observed or have a lower cost to be considered cost-effective in the United States. C1 [Morris, Bethany L.; Scott, Callie A.; Freedberg, Kenneth A.] Massachusetts Gen Hosp, Dept Med, Div Gen Med, Boston, MA 02114 USA. [Freedberg, Kenneth A.] Massachusetts Gen Hosp, Dept Med, Div Infect Dis, Boston, MA 02114 USA. [Sax, Paul E.] Brigham & Womens Hosp, Div Infect Dis, Boston, MA 02115 USA. [Sax, Paul E.; Freedberg, Kenneth A.] Harvard Univ, Sch Med, Ctr AIDS Res, Boston, MA USA. [Wilkin, Timothy J.; Gulick, Roy M.] Weill Cornell Med Coll, Dept Med, Div Infect Dis, New York, NY USA. [Schackman, Bruce R.] Weill Cornell Med Coll, Dept Publ Hlth, Div Hlth Policy, New York, NY USA. [Freedberg, Kenneth A.] Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA 02115 USA. RP Morris, BL (reprint author), 50 Staniford St,9th Floor, Boston, MA 02144 USA. EM blmorris@partners.org FU National Institute for Allergy and Infectious Diseases [R37 AI042006, AI51966, U01 A1 069472, U01 AI068636, U01 AI069419]; Gilead; Merck; GlaxoSmithKline; Tibotec; Pfizer FX This research was funded by the National Institute for Allergy and Infectious Diseases: R37 AI042006, AI51966, U01 A1 069472 (Partners/Harvard Clinical Trials Unit), U01 AI068636 (Central AIDS Clinical Trials Group) and U01 AI069419 (Cornell Clinical Trials Unit).; Dr. Wilkin has served as a paid consultant to Pfizer and Quest Diagnostics. Dr. Sax has served as a consultant to Abbott, Bristol-Myers Squibb, Gilead, GlaxoSmithKline, Merck, and Tibotec and has received grant support from Gilead, Merck, GlaxoSmithKline, and Tibotec. Dr. Gulick has served as an ad-hoc consultant to GlaxoSmithKline, Merck, Pfizer, and ViiV and has received grant support from Merck and Pfizer. NR 43 TC 5 Z9 5 U1 0 U2 1 PU THOMAS LAND PUBLISHERS, INC PI ST LOUIS PA 255 JEFFERSON RD, ST LOUIS, MO 63119 USA SN 1528-4336 J9 HIV CLIN TRIALS JI HIV Clin. Trials PD JAN-FEB PY 2012 VL 13 IS 1 BP 1 EP 10 DI 10.1310/hct1301-1 PG 10 WC Infectious Diseases; Pharmacology & Pharmacy SC Infectious Diseases; Pharmacology & Pharmacy GA 883AB UT WOS:000299603900001 PM 22306583 ER PT J AU Opravil, M Rodriguez-Torres, M Rockstroh, J Snoeck, E Chung, RT Tietz, A Torriani, FJ AF Opravil, Milos Rodriguez-Torres, Maribel Rockstroh, Juergen Snoeck, Eric Chung, Raymond T. Tietz, Andreas Torriani, Francesca J. TI The Dose-Response Relationship of Peginterferon Alfa-2a and Ribavirin in the Treatment of Patients Coinfected with HIV-HCV SO HIV CLINICAL TRIALS LA English DT Article DE HIV-HCV coinfection; peginterferon alfa-2a; SVR ID CHRONIC HEPATITIS-C; WEIGHT-BASED RIBAVIRIN; PLUS RIBAVIRIN; INFECTED PATIENTS; VIROLOGICAL RESPONSE; COMBINATION THERAPY; AMERICAN PATIENTS; VIRUS GENOTYPE-1; AFRICAN-AMERICAN; IMPACT AB Purpose: The relationship between peginterferon/ribavirin exposure and the probability of achieving a sustained virologic response (SVR) in HIV-HCV coinfected patients is not well described. We conducted a retrospective analysis of HIV-HCV coinfected patients randomized to 48 weeks of treatment with peginterferon alfa-2a (40 kD) 180 mu g/week and ribavirin 800 mg/day in the multinational APRICOT study to define optimal exposure thresholds. Method: Actual drug exposure was estimated in 287 patients, taking into consideration dose reductions for adverse events or laboratory abnormalities. Results: SVR overall and SVR in those completing treatment was, respectively, 29% and 37% among HCV genotype-1 patients and 59% and 68% among genotype non-1 patients. No patients with <= 40% exposure to ribavirin achieved an SVR. Receiver operating characteristic analysis identified that threshold exposures to both drugs of >75% (genotype-1) and >60% (genotype non-1) are associated with SVR. An existing generalized additive model populated with data from HCV monoinfected patients was updated to predict an overall SVR of 37% if genotype-1 patients received ribavirin 1000 or 1200 mg/day but at the cost of a higher incidence of anemia (23%). Conclusion: Completion of scheduled treatment and exceeding certain thresholds for exposure to peginterferon alfa 2a (40 kD) and ribavirin is associated with higher SVR rates. C1 [Torriani, Francesca J.] Univ Calif San Diego, Div Infect Dis, San Diego, CA 92103 USA. [Opravil, Milos] Hirslanden Clin Aarau, Ctr Internal Med, Aarau, Switzerland. [Rodriguez-Torres, Maribel] Fdn Invest Diego, CCTI, Sancture, PR USA. [Rockstroh, Juergen] Univ Bonn, Dept Med, Bonn, Germany. [Snoeck, Eric] Exprimo NV, Mechelen, Belgium. [Chung, Raymond T.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastrointestinal Unit, Boston, MA USA. [Tietz, Andreas] Roche, Basel, Switzerland. RP Torriani, FJ (reprint author), Univ Calif San Diego, Div Infect Dis, 200 W Arbor Dr,MB 136,Room 100, San Diego, CA 92103 USA. EM ftorriani@ucsd.edu FU F. Hoffmann-La Roche Ltd.; Vertex; Anadys; Roche; GlaxoSmithKline; Novartis; Bristol-Myers Squibb; Idera; Pharmasset; sanofi-aventis; Merck; Abbott Labs; Pfizer; Human Genome Sciences; Gilead; Johnson Johnson; Zymogenetics; Akros; Scynexis; Santaris; Mochida; Boehringer; Inhibitex; Idenix; Siemens FX This study was sponsored by F. Hoffmann-La Roche Ltd. Support for third-party writing assistance for this manuscript was provided by F. Hoffmann-La Roche Ltd.; Maribel Rodriguez-Torres, MD, CPI, is a consultant for Hoffman La Roche, Abbott Labs, Anadys, Pharmasset, Akros, Genentech, Bristol-Myers Squibb, Novartis, and Merck. She has received grant/research support from Vertex, Anadys, Roche, GlaxoSmithKline, Novartis, Bristol-Myers Squibb, Idera, Pharmasset, sanofi-aventis, Merck, Abbott Labs, Pfizer, Human Genome Sciences, Gilead, Johnson & Johnson, Zymogenetics, Akros, Scynexis, Santaris, Mochida, Boehringer, Inhibitex, Idenix, and Siemens. NR 25 TC 4 Z9 4 U1 1 U2 1 PU THOMAS LAND PUBLISHERS, INC PI ST LOUIS PA 255 JEFFERSON RD, ST LOUIS, MO 63119 USA SN 1528-4336 J9 HIV CLIN TRIALS JI HIV Clin. Trials PD JAN-FEB PY 2012 VL 13 IS 1 BP 33 EP 45 DI 10.1310/hct1301-33 PG 13 WC Infectious Diseases; Pharmacology & Pharmacy SC Infectious Diseases; Pharmacology & Pharmacy GA 883AB UT WOS:000299603900004 PM 22306586 ER PT J AU Tam, JM Mansour, MK Khan, NS Yoder, NC Vyas, JM AF Tam, Jenny M. Mansour, Michael K. Khan, Nida S. Yoder, Nicholas C. Vyas, Jatin M. TI Use of fungal derived polysaccharide-conjugated particles to probe Dectin-1 responses in innate immunity SO INTEGRATIVE BIOLOGY LA English DT Article ID BETA-GLUCANS; RECOGNITION; RECEPTOR; PHAGOCYTOSIS; ACTIVATION; IDENTIFICATION; CANDIDIASIS; MACROPHAGES; PHAGOSOMES; INDUCTION AB The number of life-threatening fungal infections has risen in immunocompromised patients, and identification of the rules that govern an appropriate immune response is essential to develop better diagnostics and targeted therapeutics. The outer cell wall component on pathogenic fungi consists of beta-1,3-glucan, and Dectin-1, a pattern recognition receptor present on the cell surface of innate immune cells, binds specifically to this carbohydrate. A barrier in understanding the exact immunological response to pathogen-derived carbohydrate epitopes is the presence of multiple types of carbohydrate moieties on fungal cell walls. To dissect the immunological mechanisms used to recognize pathogens, a system of "fungal like particles" was developed that consisted of polystyrene beads, which mimicked the three dimensional shape of the fungus, coated covalently with purified beta-1,3-glucan derived from Saccharomyces cerevisiae. The morphology of the beta-1,3-glucan layer was examined by immunofluorescence, flow cytometery, and immuno-transmission electron microscopy. The covalent linkages of the beta-1,3-glucan to the polystyrene surface were stable after subjecting the beads to detergents. By pre-treating beta-1,3-glucan beads with laminarinase, a specific beta-1,3-gluconase, the reactivity of the anti-beta-1,3-glucan antibody was abrogated in comparison to treatment with proteinase K indicating that the coating of these beads was predominantly beta-1,3-glucan. TNF-alpha was also measured by stimulating bone-marrow derived macrophages with the beta-1,3-glucan beads, and showed a dose dependent response compared to soluble beta-glucan, insoluble beta-1,3-glucan, uncoated beads, and soluble beta-1,3-glucan mixed with uncoated beads. Finally, beta-1,3-glucan beads were incubated with GFP-Dectin-1 expressing macrophages and imaged using confocal microscopy. beta-1,3-beads were taken up within minutes and retained Dectin-1 recruitment to the phagosome as compared to uncoated beads. These data describe a unique fungal-like particle system that will permit immunologists to probe the critical steps in early recognition of pathogen-derived fungal carbohydrate antigens by innate immune cells. C1 [Yoder, Nicholas C.] Nine Cambridge Ctr, Whitehead Inst Biomed Res, Cambridge, MA 02142 USA. [Tam, Jenny M.; Mansour, Michael K.; Khan, Nida S.; Vyas, Jatin M.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med,Div Infect Dis, Boston, MA 02114 USA. RP Tam, JM (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med,Div Infect Dis, 55 Fruit St,GRJ 5-504, Boston, MA 02114 USA. EM jvyas@partners.org RI Vyas, Jatin/Q-1627-2016 OI Vyas, Jatin/0000-0002-9985-9565 FU Inflammatory Bowel Disease Grant [DK43351]; Boston Area Diabetes and Endocrinology Research Center [DK57521]; Department of Medicine; Clay Fellowship; MGH Department of Medicine; MGH ECOR; NIAID, NIH [1R01AI092084-01A1] FX We thank Dr David Underhill and Dr Douglas Golenbock for sharing reagents. Electron microscopy was performed by Mary McKee in the Microscopy Core of the Center for Systems Biology/Program in Membrane Biology, Massachusetts General Hospital, Boston, which is partially supported by an Inflammatory Bowel Disease Grant DK43351 and a Boston Area Diabetes and Endocrinology Research Center Award DK57521. JMT, MKM, and NK were supported by the Department of Medicine internal funds. NCY was supported by the Clay Fellowship. JMV was supported in part by MGH Department of Medicine internal funds, MGH ECOR funds, and the NIAID, NIH (1R01AI092084-01A1). NR 31 TC 11 Z9 11 U1 3 U2 13 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 1757-9694 J9 INTEGR BIOL-UK JI Integr. Biol. PY 2012 VL 4 IS 2 BP 220 EP 227 DI 10.1039/c2ib00089j PG 8 WC Cell Biology SC Cell Biology GA 883NK UT WOS:000299640700011 PM 22200052 ER PT J AU Armstrong, EJ Yeo, KK Javed, U Mahmud, E Patel, M Shunk, KA MacGregor, JS Low, RI Rogers, JH AF Armstrong, Ehrin J. Yeo, Khung Keong Javed, Usman Mahmud, Ehtisham Patel, Mitul Shunk, Kendrick A. MacGregor, John S. Low, Reginald I. Rogers, Jason H. TI Angiographic Stent Thrombosis at Coronary Bifurcations Short- and Long-Term Prognosis SO JACC-CARDIOVASCULAR INTERVENTIONS LA English DT Article DE bifurcation; stent thrombosis; thrombus ID DRUG-ELUTING STENTS; ELEVATION MYOCARDIAL-INFARCTION; IMPLANTATION; REGISTRY; LESIONS; RISK; PREDICTORS; SIROLIMUS; TRIALS AB Objectives This study sought to describe the presentation, management, and outcomes of patients presenting with angiographic definite stent thrombosis (ST) at coronary bifurcations. Background The development of drug-eluting stents has made it increasingly feasible to treat bifurcation lesions percutaneously. However, ST at coronary bifurcations may be associated with greater mortality than ST elsewhere. Methods We analyzed a multicenter California registry comprising all cases of angiographic definite ST at 5 academic hospitals from 2005 to 2010. Stenting was defined as occurring at a bifurcation if the main vessel stent crossed a side branch >= 2.0 mm in diameter (provisional single-stent approach), or if there was a prior 2-stent bifurcation approach. Results Among 173 cases of angiographic definite ST, we identified 20 cases of ST at coronary bifurcations. Nine of 20 bifurcation ST (45%) occurred with a stent present in both the parent and branch vessel. Eight cases had thrombus present in both the parent and side branch vessels. In-hospital mortality was much higher for subjects with bifurcation ST than ST at a nonbifurcation site (20% vs. 2%, p < 0.0001). During a median follow-up of 2.3 years, ST at a coronary bifurcation was associated with increased long-term mortality (hazard ratio [HR]: 3.3, 95% confidence interval [Cl]: 1.4 to 7.7, p = 0.007) and a significantly higher risk for major adverse cardiovascular events (HR: 2.2, 95% Cl: 1.04 to 4.8, p = 0.04) relative to ST at a nonbifurcation site. Conclusions ST at coronary bifurcations is associated with a higher in-hospital and long-term mortality than ST at nonbifurcation lesions. (Stent Thrombus in Acute Coronary Syndromes; NCT00931502) (J Am Coll Cardiol Intv 2012;5:57-63) (C) 2012 by the American College of Cardiology Foundation C1 [Armstrong, Ehrin J.; Yeo, Khung Keong; Javed, Usman; Low, Reginald I.; Rogers, Jason H.] Univ Calif Davis, Davis Med Ctr, Div Cardiovasc Med, Sacramento, CA 95817 USA. [Mahmud, Ehtisham; Patel, Mitul] Univ Calif San Diego, Med Ctr, Div Cardiol, San Diego, CA 92103 USA. [Shunk, Kendrick A.; MacGregor, John S.] Univ Calif San Francisco, Div Cardiol, Med Ctr, San Francisco, CA USA. [Shunk, Kendrick A.] San Francisco VA Med Ctr, Div Cardiol, San Francisco, CA USA. [MacGregor, John S.] San Francisco Gen Hosp, Div Cardiol, San Francisco, CA 94110 USA. RP Rogers, JH (reprint author), Univ Calif Davis, Davis Med Ctr, Div Cardiovasc Med, 4860 Y St,Suite 2820, Sacramento, CA 95817 USA. EM jason.rogers@ucdmc.ucdavis.edu FU Boston Scientific; Abbott Vascular; Accumetrics; sanofi-aventis FX Dr. Mahmud serves on the Speaker's Bureau for Medtronic and Eli Lilly; is a consultant for Eli Lilly; and receives research support from Boston Scientific, Abbott Vascular, Accumetrics, and sanofi-aventis. Dr. Low is on the advisory board of and is a consultant for Abbott Vascular and Boston Scientific. Dr. Rogers is a consultant for Volcano, Medtronic, and Boston Scientific. All other authors have reported that they have relationships relevant to the contents of this paper to disclose. NR 21 TC 7 Z9 7 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1936-8798 J9 JACC-CARDIOVASC INTE JI JACC-Cardiovasc. Interv. PD JAN PY 2012 VL 5 IS 1 BP 57 EP 63 DI 10.1016/j.jcin.2011.09.015 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 883XU UT WOS:000299669000008 PM 22230151 ER PT J AU Berenz, EC Vujanovic, AA Coffey, SF Zvolensky, MJ AF Berenz, Erin C. Vujanovic, Anka A. Coffey, Scott F. Zvolensky, Michael J. TI Anxiety sensitivity and breath-holding duration in relation to PTSD symptom severity among trauma exposed adults SO JOURNAL OF ANXIETY DISORDERS LA English DT Article DE PTSD; Trauma; Distress tolerance; Anxiety sensitivity ID POSTTRAUMATIC-STRESS-DISORDER; DISTRESS TOLERANCE; PANIC DISORDER; PSYCHOMETRIC PROPERTIES; REACTIVITY; HYPERVENTILATION; PSYCHOPATHOLOGY; INDIVIDUALS; INTOLERANCE; VALIDATION AB The present investigation examined the main and interactive effects of anxiety sensitivity and behavioral distress tolerance, indexed using the breath-holding task, in relation to PTSD symptom severity among trauma-exposed adults. Participants were 88 adults (63.6% women; M-age = 22.9, SD = 9.1, range = 18-62), recruited from the community, who met DSM-IV-TR PTSD Criterion A for lifetime trauma exposure. Covariates included number of potentially traumatic events, nonclinical panic attack history, and participant sex. Anxiety sensitivity was significantly incrementally associated with PTSD total symptom severity, as well as Avoidance and Hyperarousal symptom severity (p's < .01). Breath-holding duration was not significantly related to PTSD symptom severity (p's > .05). However, breath-holding duration emerged as a significant moderator of the association between anxiety sensitivity and PTSD Avoidance symptom severity, such that lower breath-holding duration exacerbated the effect of heightened anxiety sensitivity with regard to PTSD Avoidance symptom severity. (C) 2011 Elsevier Ltd. All rights reserved. C1 [Berenz, Erin C.; Coffey, Scott F.] Univ Mississippi, Med Ctr, Dept Psychiat, Jackson, MS 39216 USA. [Berenz, Erin C.; Zvolensky, Michael J.] Univ Vermont, Dept Psychol, Burlington, VT 05405 USA. [Berenz, Erin C.] GV Sonny Montgomery VA Med Ctr, Jackson, MS 39216 USA. [Vujanovic, Anka A.] Boston Univ, Sch Med, Div Psychiat, Boston, MA 02130 USA. [Vujanovic, Anka A.] VA Boston Hlth Care Syst, Natl Ctr PTSD Behav Sci Div, Boston, MA 02130 USA. RP Berenz, EC (reprint author), Univ Mississippi, Med Ctr, Dept Psychiat, 2500 N State St, Jackson, MS 39216 USA. EM emarshall2@umc.edu FU NIDA NIH HHS [R01 DA027533, 1 R01 DA027533-01]; NIMH NIH HHS [1 R01 MH076629-01, F31 MH080453, 1 F31 MH080453-01A1, R01 MH076629, F31 MH080453-01A1] NR 43 TC 19 Z9 19 U1 5 U2 12 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0887-6185 J9 J ANXIETY DISORD JI J. Anxiety Disord. PD JAN PY 2012 VL 26 IS 1 BP 134 EP 139 DI 10.1016/j.janxdis.2011.10.004 PG 6 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 879VU UT WOS:000299361800018 PM 22047652 ER PT J AU Walcott, BP Nahed, BV Sarpong, Y Kahle, KT Sekhar, LN Ferreira, MJ AF Walcott, Brian P. Nahed, Brian V. Sarpong, Yaw Kahle, Kristopher T. Sekhar, Laligam N. Ferreira, Manuel J. TI Incidence of cerebrospinal fluid leak following petrosectomy and analysis of avoidance techniques SO JOURNAL OF CLINICAL NEUROSCIENCE LA English DT Article DE Aneurysm; CSF; Petrosectomy; Skull base; Temporalis; Tumor; Vascularized flap ID CRANIAL BASE RECONSTRUCTION; FREE-TISSUE TRANSFER; MUSCLE FLAP; SURGERY; DEFECTS AB A cerebrospinal fluid (CSF) leak following skull base surgery can lead to meningitis, impaired wound healing, and often requires re-operation and/or CSF diversion. Thirty-two patients underwent a presigmoid, transpetrosal approach to skull base aneurysms and tumors. A vascularized temporalis muscle flap was utilized during the closure of the initial skull base reconstruction in 18 of the 32 patients. A temporary CSF diversion was utilized in 23 of the 32 patients. A permanent shunt was placed in eight patients. One patient developed a postoperative CSF leak from the contralateral ear due to a congenital abnormality in the middle ear. Another patient, who did not have a vascularized temporalis muscle flap reconstruction, developed a postoperative CSF leak in the context of an operation for recurrent tumor and prior radiation treatment. CSF diversion and vascularized temporalis muscle flaps are effective in preventing the development of postoperative CSF leaks following petrosectomy. (C) 2011 Elsevier Ltd. All rights reserved. C1 [Sarpong, Yaw; Sekhar, Laligam N.; Ferreira, Manuel J.] Univ Washington, Sch Med, Dept Neurosurg, Seattle, WA 98104 USA. [Walcott, Brian P.; Nahed, Brian V.; Kahle, Kristopher T.] Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. [Walcott, Brian P.; Nahed, Brian V.; Kahle, Kristopher T.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Ferreira, MJ (reprint author), Univ Washington, Sch Med, Dept Neurosurg, Box 359766,325 9th Ave, Seattle, WA 98104 USA. EM manuelf3@u.washington.edu NR 24 TC 5 Z9 5 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0967-5868 J9 J CLIN NEUROSCI JI J. Clin. Neurosci. PD JAN PY 2012 VL 19 IS 1 BP 92 EP 94 DI 10.1016/j.jocn.2011.08.001 PG 3 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 882YP UT WOS:000299600100016 PM 22104349 ER PT J AU Walcott, BP Nahed, BV Kahle, KT Sekhar, LN Ferreira, MJ AF Walcott, Brian P. Nahed, Brian V. Kahle, Kristopher T. Sekhar, Laligam N. Ferreira, Manuel J. TI Cerebrovascular bypass and aneurysm trapping for the treatment of an A2-segment anterior cerebral artery pseudoaneurysm and herniation through a skull base defect following trauma SO JOURNAL OF CLINICAL NEUROSCIENCE LA English DT Article DE Aneurysm; Trauma; Bypass; Skull base; Pseudoaneurysm ID PIPELINE EMBOLIZATION DEVICE; INTRACRANIAL ANEURYSMS; REVASCULARIZATION; EXPERIENCE AB Fractures of the anterior skull base can lead to pseudoaneurysm formation as a result of direct injury to a vessel wall. Pseudoaneurysms in this location are challenging to treat, as both perforator and distal blood supply must be maintained. Additionally, traumatic skull base fractures can lead to a rare condition of cerebral blood vessel herniation through the bony defect, further complicating treatment planning. Treatment of these lesions is essential to (1) prevent the occurrence of potentially fatal subarachnoid hemorrhage and (2) prevent dissection from propagating and compromising blood flow to distal vessels, perforators, and even parent vessels. We present a unique case of a traumatic proximal anterior cerebral artery pseudoaneurysm, herniating through a skull base defect. Treatment consisted of aneurysm trapping and bypass with skull base reconstruction. (C) 2011 Elsevier Ltd. All rights reserved. C1 [Sekhar, Laligam N.; Ferreira, Manuel J.] Univ Washington, Sch Med, Dept Neurosurg, Seattle, WA 98104 USA. [Walcott, Brian P.; Nahed, Brian V.; Kahle, Kristopher T.] Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA USA. [Walcott, Brian P.; Nahed, Brian V.; Kahle, Kristopher T.] Harvard Univ, Sch Med, Boston, MA USA. RP Ferreira, MJ (reprint author), Univ Washington, Sch Med, Dept Neurosurg, Box 359766,325 9th Ave, Seattle, WA 98104 USA. EM manuelf3@u.washington.edu NR 10 TC 4 Z9 4 U1 0 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0967-5868 J9 J CLIN NEUROSCI JI J. Clin. Neurosci. PD JAN PY 2012 VL 19 IS 1 BP 149 EP 151 DI 10.1016/j.jocn.2011.05.017 PG 3 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 882YP UT WOS:000299600100030 PM 22051032 ER PT J AU Stapleton, CJ Walcott, BP Kahle, KT Codd, PJ Nahed, BV Chen, L Robison, NJ Delalle, I Goumnerova, LC Jackson, EM AF Stapleton, Christopher J. Walcott, Brian P. Kahle, Kristopher T. Codd, Patrick J. Nahed, Brian V. Chen, Li Robison, Nathan J. Delalle, Ivana Goumnerova, Liliana C. Jackson, Eric M. TI Diffuse central neurocytoma with craniospinal dissemination SO JOURNAL OF CLINICAL NEUROSCIENCE LA English DT Article DE Neurocytoma; Neuroectodermal tumors; Spinal cord neoplasms ID TUMOR AB Central neurocytomas (CN) are benign central nervous system (CNS) tumors of neuroglial origin that represent 0.25 to 0.5% of all intracranial tumors in adults and an even smaller proportion of pediatric CNS tumors. These tumors characteristically occur in the subependymal layer of the lateral ventricle near the foramen of Monro and appear as sharply demarcated, solitary lesions. Surgical resection is considered curative, as the reported recurrence rate is less than 5% for patients with localized disease. In this report, we describe the case of a three-year-old boy with a diffuse CN with craniospinal dissemination identified at the time of diagnosis. Given the extensive nature of the disease, surgical resection was not indicated and he underwent a chemotherapeutic regimen of vincristine and carboplatin. At 18 months followup, the patient has completed 6 of 8 total cycles of vincristine and carboplatin and serial imaging shows stable disease within the craniospinal axis. (C) 2011 Elsevier Ltd. All rights reserved. C1 [Stapleton, Christopher J.; Walcott, Brian P.; Kahle, Kristopher T.; Codd, Patrick J.; Nahed, Brian V.] Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. [Stapleton, Christopher J.; Walcott, Brian P.; Kahle, Kristopher T.; Codd, Patrick J.; Nahed, Brian V.; Chen, Li; Delalle, Ivana; Goumnerova, Liliana C.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Chen, Li; Delalle, Ivana] Childrens Hosp, Dept Neuropathol, Boston, MA 02114 USA. [Robison, Nathan J.] Childrens Hosp, Dept Neurooncol, Boston, MA 02114 USA. [Robison, Nathan J.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Goumnerova, Liliana C.] Childrens Hosp, Dept Neurosurg, Boston, MA 02114 USA. [Jackson, Eric M.] Nationwide Childrens Hosp, Dept Neurosurg, Columbus, OH 43210 USA. [Jackson, Eric M.] Ohio State Univ, Coll Med, Columbus, OH 43210 USA. RP Walcott, BP (reprint author), Massachusetts Gen Hosp, Dept Neurosurg, 55 Fruit St,White Bldg,Room 502, Boston, MA 02114 USA. EM walcott.brian@mgh.harvard.edu OI Jackson, Eric/0000-0001-9306-9290 NR 15 TC 6 Z9 6 U1 0 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0967-5868 J9 J CLIN NEUROSCI JI J. Clin. Neurosci. PD JAN PY 2012 VL 19 IS 1 BP 163 EP 166 DI 10.1016/j.jocn.2011.07.016 PG 4 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 882YP UT WOS:000299600100035 PM 22088950 ER PT J AU Wong, KK Muller, MLTM Kuwabara, H Studenski, SA Bohnen, NI AF Wong, Ka Kit Mueller, Martijn L. T. M. Kuwabara, Hiroto Studenski, Stephanie A. Bohnen, Nicolaas I. TI Gender differences in nigrostriatal dopaminergic innervation are present at young-to-middle but not at older age in normal adults SO JOURNAL OF CLINICAL NEUROSCIENCE LA English DT Article DE Aging; Gender; Basal ganglia; Dopamine; Menopause; Parkinson's disease; Positron emission tomography ID SEX-DIFFERENCES; TRANSPORTER AVAILABILITY; SPECT AB Gender differences in brain dopaminergic activity have been variably reported in the literature. We performed an evaluation for gender effects on striatal dopamine transporter (DAT) binding in a group of normal subjects. Community-dwelling adults (n = 85, 50F/35M, mean age 62.7 +/- 16.2 SD, range 20-85) underwent DAT[C-11]-beta-carbomethoxy-3 beta-(4-fluorophenyl) tropane (beta-CFT) positron emission tomography (PET) imaging. Gender effects for DAT binding were compared using ANCOVA for two subgroups; young-to-middle aged adults and older adults, using an age threshold of 60 years. There were 54 subjects (24M/30F; mean age 72.9 +/- 7.3) 60 years and older and 31 (11M/20F; mean age 45.0 +/- 11.4) subjects younger than 60. Age-adjusted striatal DAT gender effects were present in the young-to-middle (F = 10.4, P = 0.003) but not in the elderly age group (F = 0.5, ns). Gender differences in nigrostriatal dopaminergic innervation are present, with higher levels of DAT binding in young-to-middle age women compared to men, but not present in the elderly. Published by Elsevier Ltd. C1 [Wong, Ka Kit; Bohnen, Nicolaas I.] VA Ann Arbor Healthcare Syst, GRECC, Ann Arbor, MI USA. [Mueller, Martijn L. T. M.; Bohnen, Nicolaas I.] Univ Michigan, Funct Neuroimaging Cognit & Mobil Lab, Dept Radiol, Ann Arbor, MI 48105 USA. [Mueller, Martijn L. T. M.; Bohnen, Nicolaas I.] Univ Michigan, Funct Neuroimaging Cognit & Mobil Lab, Dept Neurol, Ann Arbor, MI 48105 USA. [Kuwabara, Hiroto] Johns Hopkins Univ, Dept Radiol, Baltimore, MD USA. [Studenski, Stephanie A.] VA Pittsburgh Healthcare Syst, GRECC, Pittsburgh, PA USA. [Studenski, Stephanie A.] Univ Pittsburgh, Sch Med, Dept Med, Div Geriatr Med, Pittsburgh, PA USA. [Wong, Ka Kit] Univ Michigan, Dept Nucl Med Radiol, Ann Arbor, MI 48105 USA. RP Bohnen, NI (reprint author), VA Ann Arbor Healthcare Syst, GRECC, Ann Arbor, MI USA. EM nbohnen@umich.edu FU Department of Veterans Affairs FX This study was funded by the Department of Veterans Affairs. NR 7 TC 14 Z9 14 U1 0 U2 4 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0967-5868 J9 J CLIN NEUROSCI JI J. Clin. Neurosci. PD JAN PY 2012 VL 19 IS 1 BP 183 EP 184 DI 10.1016/j.jocn.2011.05.013 PG 2 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 882YP UT WOS:000299600100042 PM 22030267 ER PT J AU Aspinall, SL Good, CB Cunningham, FE AF Aspinall, Sherrie L. Good, Chester B. Cunningham, Francesca E. TI Glycemic Control Was Unchanged in Veterans Health Administration Patients Converted from Glyburide to Glipizide SO JOURNAL OF MANAGED CARE PHARMACY LA English DT Letter C1 [Aspinall, Sherrie L.; Good, Chester B.; Cunningham, Francesca E.] VA Ctr Medicat Safety, Hines, IL USA. [Good, Chester B.] VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA USA. [Aspinall, Sherrie L.; Good, Chester B.] Univ Pittsburgh, Sch Pharm, Pittsburgh, PA USA. [Good, Chester B.] Univ Pittsburgh, Sch Med, Pittsburgh, PA USA. RP Aspinall, SL (reprint author), VA Ctr Medicat Safety, Hines, IL USA. EM sherrie.aspinall@va.gov NR 3 TC 0 Z9 0 U1 2 U2 2 PU ACAD MANAGED CARE PHARMACY PI ALEXANDRIA PA 100 N PITT ST, 400, ALEXANDRIA, VA 22314-3134 USA SN 1083-4087 J9 J MANAGE CARE PHARM JI J. Manag. Care Pharm. PD JAN-FEB PY 2012 VL 18 IS 1 BP 73 EP 73 PG 1 WC Health Care Sciences & Services; Pharmacology & Pharmacy SC Health Care Sciences & Services; Pharmacology & Pharmacy GA 885BI UT WOS:000299753100007 PM 22235958 ER PT J AU O'Farrell, TJ Clements, K AF O'Farrell, Timothy J. Clements, Kahni TI Review of Outcome Research on Marital and Family Therapy in Treatment for Alcoholism SO JOURNAL OF MARITAL AND FAMILY THERAPY LA English DT Review ID BEHAVIORAL COUPLES THERAPY; INTIMATE PARTNER VIOLENCE; RANDOMIZED CONTROLLED-TRIAL; SUBSTANCE-ABUSING PATIENTS; INPATIENT DETOXIFICATION; TREATMENT INTERVENTION; RELAPSE PREVENTION; SIGNIFICANT OTHERS; HEAVY DRINKERS; USE DISORDERS AB This review of controlled studies of marital and family therapy (MFT) in alcoholism treatment updates the earlier review by OFarrell and Fals-Stewart (2003). We conclude that, when the alcoholic is unwilling to seek help, MFT is effective in helping the family cope better and motivating alcoholics to enter treatment. Specifically, both Al-Anon facilitation and referral and spouse coping skills training (based on new findings) help family members cope better, and CRAFT promotes treatment entry and was successfully transported to a community clinic in a new study. Once the alcoholic enters treatment, MFT, particularly behavioral couples therapy (BCT), is clearly more effective than individual treatment at increasing abstinence and improving relationship functioning. New BCT studies showed efficacy with women alcoholics and with gay and lesbian alcoholics, and BCT was successfully transported to a community clinic, a brief BCT version was tested, and BCT was adapted for family members other than spouses. Future studies should evaluate the following: MFT with couples where both members have a current alcohol problem and with minority patients, mechanisms of change, transportability of evidence-based MFT approaches to clinical practice settings, and replication of MFT outcomes of reduced partner violence and improved child functioning. C1 [O'Farrell, Timothy J.; Clements, Kahni] Harvard Univ, Sch Med, Dept Psychiat, VA Boston Healthcare Syst, Cambridge, MA 02138 USA. RP O'Farrell, TJ (reprint author), VAMC 116B1,940 Belmont St, Brockton, MA 02301 USA. EM timothy_ofarrell@hms.harvard.edu FU NIAAA NIH HHS [R01AA017865, R01 AA017865, R01 AA017865-01A1] NR 95 TC 41 Z9 43 U1 4 U2 43 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0194-472X J9 J MARITAL FAM THER JI J. Marital Fam. Ther. PD JAN PY 2012 VL 38 IS 1 BP 122 EP 144 DI 10.1111/j.1752-0606.2011.00242.x PG 23 WC Psychology, Clinical; Family Studies SC Psychology; Family Studies GA 883KO UT WOS:000299633100007 PM 22283384 ER PT J AU Susarla, SM Peacock, ZS Alam, HB AF Susarla, Srinivas M. Peacock, Zachary S. Alam, Hasan B. TI Percutaneous Dilatational Tracheostomy: Review of Technique and Evidence for Its Use SO JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY LA English DT Review ID INTENSIVE-CARE-UNIT; CRITICALLY-ILL PATIENTS; CONVENTIONAL SURGICAL TRACHEOSTOMY; TERM-FOLLOW-UP; DILATIONAL TRACHEOSTOMY; RANDOMIZED-TRIAL; BEDSIDE; TRACHEOTOMY; COST; TRANSPORT AB Tracheostomy is a technique for airway management commonly used by surgeons who care for critically ill patients. Patients with traumatic facial injuries, severe odontogenic infections, and head and neck malignancies are often recipients of tracheostomies. As such, the oral and maxillofacial surgeon who frequently treats such patients should be well-trained in tracheostomy placement. For decades, the standard technique for tracheostomy was the open surgical technique. However, during the past 20 years, the use of percutaneous dilatational tracheostomy has increased. The purpose of the present report is to review the percutaneous dilatational tracheostomy technique, describe the use of intensive care units as proxies for the operating room, and review the available evidence comparing percutaneous dilatational tracheostomy to open tracheostomy. (C) 2012 American Association of Oral and Maxillofacial Surgeons J Oral Maxillofac Surg 70:74-82, 2012 C1 [Susarla, Srinivas M.; Peacock, Zachary S.] Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Boston, MA 02114 USA. [Alam, Hasan B.] Harvard Univ, Sch Med, Boston, MA USA. RP Susarla, SM (reprint author), Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, WACC230, Boston, MA 02114 USA. EM ssusarla1@partners.org OI Susarla, Srinivas/0000-0003-0155-8260 FU Oral and Maxillofacial Surgery Foundation; Massachusetts General Hospital Department of Oral and Maxillofacial Surgery; Center for Applied Clinical Investigation FX This work was supported by the Oral and Maxillofacial Surgery Foundation Fellowship in Clinical Investigation (to S. M. S.), the Massachusetts General Hospital Department of Oral and Maxillofacial Surgery Education and Research Fund (to S. M. S. and Z.S.P.), and the Center for Applied Clinical Investigation (to S.M.S.). NR 39 TC 9 Z9 10 U1 0 U2 3 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0278-2391 J9 J ORAL MAXIL SURG JI J. Oral Maxillofac. Surg. PD JAN PY 2012 VL 70 IS 1 BP 74 EP 82 DI 10.1016/j.joms.2011.04.002 PG 9 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 877WX UT WOS:000299214500033 PM 21820231 ER PT J AU Lawler, ME Hansen, GM Williams, WB Susarla, SM Faquin, WC Troulis, MJ Kaban, LB AF Lawler, Matthew E. Hansen, Gentry M. Williams, W. Bradford Susarla, Srinivas M. Faquin, William C. Troulis, Maria J. Kaban, Leonard B. TI Serial Histologic and Immunohistochemical Changes in Anterior Digastric Myocytes in Response to Distraction Osteogenesis SO JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY LA English DT Article ID SKELETAL-MUSCLE FIBERS; SATELLITE CELL; HISTOMORPHOMETRIC EVALUATION; MYONUCLEAR NUMBER; BONE DISTRACTION; MASSETER MUSCLE; GROWTH; TISSUE; REGENERATION; DIFFERENTIATION AB Purpose: To document histologic and immunohistochemical changes in the anterior digastric muscle during distraction osteogenesis (DO). Materials and Methods: Nineteen Yucatan minipigs with mixed dentition were used for these experiments. Group A (n = 16) underwent unilateral mandibular distraction at a rate of 1 mm/day (no latency) for 12 days. Animals were killed at mid-DO (n = 5), end-DO (n = 5), mid-fixation (n = 4), and end-fixation (n = 2). Group B (n = 2) underwent acute 12-mm advancement, and group C (n = 1) dissection and osteotomy. Animals from groups B and C were killed at the end-DO time point. Digastric muscles from treatment and contralateral sides of all animals were harvested and embedded in paraffin. Specimens were stained with hematoxylin/eosin or immunohistochemically for proliferating cell nuclear antigen (PCNA; total cell proliferation), paired Box-7 gene protein (Pax7; satellite cells), or myogenic differentiation 1 protein (MyoD; differentiating myoblasts). Descriptive and bivariate statistics were computed to compare groups (P <= .05 statistically significant). Results: All animals survived the operation and observation period; there were no device failures. Two animals (1 at mid-DO, 1 at mid-fixation) were eliminated from the study because of postoperative infection. There was minimal digastric inflammation, fibrosis, and muscle fiber size variability during active DO. Immunohistochemical analysis showed statistically significant increases in PCNA (cellular proliferation), Pax7 (satellite cells), and MyoD (differentiating myoblasts) positive nuclei in digastrics at mid-DO and end-DO. Conclusions: Results of this study indicate that there are minimal pathologic changes but significant increases in PCNA, Pax7, and MyoD positive nuclei during active distraction. This supports the hypothesis that the digastric muscle response to DO consists of proliferation and hypertrophy. (C) 2012 American Association of Oral and Maxillofacial Surgeons J Oral Maxillofac Surg 70:168-178, 2012 C1 [Williams, W. Bradford; Susarla, Srinivas M.; Kaban, Leonard B.] Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Boston, MA 02114 USA. [Lawler, Matthew E.] Dept Pediat Oral & Maxillofacial Surg, Boston, MA USA. [Lawler, Matthew E.; Hansen, Gentry M.] Harvard Univ, Sch Dent Med, Boston, MA 02115 USA. [Faquin, William C.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Troulis, Maria J.] Dept Oral & Maxillofacial Surg, Boston, MA USA. RP Kaban, LB (reprint author), Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, 55 Fruit St,WRN1201, Boston, MA 02114 USA. EM lkaban@partners.org OI Susarla, Srinivas/0000-0003-0155-8260 FU AO-ASIF Foundation (Berne, Switzerland); Hanson Foundation (Boston, MA); Synthes CMF (West Chester, PA); Oral and Maxillofacial Surgery Foundation; Massachusetts General Hospital (Boston, MA) FX This project was funded in part by the AO-ASIF Foundation (Berne, Switzerland), the Hanson Foundation (Boston, MA), Synthes CMF (West Chester, PA), the Oral and Maxillofacial Surgery Foundation Fellowship in Clinical Investigation, and the Massachusetts General Hospital Oral and Maxillofacial Surgery Education and Research Fund (Boston, MA). NR 57 TC 3 Z9 3 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 0278-2391 J9 J ORAL MAXIL SURG JI J. Oral Maxillofac. Surg. PD JAN PY 2012 VL 70 IS 1 BP 168 EP 178 DI 10.1016/j.joms.2011.01.016 PG 11 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 877WX UT WOS:000299214500045 PM 21549468 ER PT J AU Tanner, JM Chang, TI Harada, ND Santiago, SM Weinreb, JE Friedlander, AH AF Tanner, Jeffrey M. Chang, Tina I. Harada, Nancy D. Santiago, Silverio M. Weinreb, Jane E. Friedlander, Arthur H. TI Prevalence of Comorbid Obstructive Sleep Apnea and Metabolic Syndrome: Syndrome Z and Maxillofacial Surgery Implications SO JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY LA English DT Article ID INSULIN-RESISTANCE; CARDIOVASCULAR-DISEASE; DIABETES-MELLITUS; ABDOMINAL OBESITY; APNOEA/HYPOPNOEA SYNDROME; MORBID-OBESITY; BLOOD-PRESSURE; FATTY-ACIDS; RISK-FACTOR; FOLLOW-UP AB Purpose: To determine the prevalence of the recently identified syndrome Z (SZ), which is the co-occurrence of obstructive sleep apnea (OSA; hypoxia, systemic and pulmonary hypertension, nocturnal arrhythmias) and metabolic syndrome (MetS; increased abdominal girth, hypertriglyceridemia, decreased high-density lipoprotein, hypertension, increased fasting glucose), which places the surgical patient at heightened risk of perioperative complications (myocardial infarction, stroke, pneumonia, wound infection). Materials and Methods: Electronic medical records of 296 male veterans were assessed for the presence of SZ using the American Academy of Sleep Medicine definition of OSA and a modified Adult Treatment Panel III definition of MetS, where obesity was defined by a body mass index of at least 30 kg/m2 rather than by waist circumference. Results: SZ was diagnosed in 59% of patients. These individuals commonly exhibited severe OSA and least commonly mild OSA. The more severe the OSA, the more likely (60%) that patients manifested moderate (4 risk markers) or severe (5 risk markers) MetS. Furthermore, with increasing apnea-hypopnea index values, the more severe were the MetS elements. Conclusions: The results of this study demonstrate the high prevalence rate of MetS in patients with OSA seeking treatment. Given the risk of perioperative complications, it is suggested that all patients scheduled for maxillofacial surgical procedures to treat OSA be evaluated for SZ. This is a US government work. There are no restrictions on its use. Published by Elsevier Inc on behalf of the American Association of Oral and Maxillofacial Surgeons. J Oral Maxillofac Surg 70:179-187, 2012 C1 [Tanner, Jeffrey M.] VA Greater Los Angeles Healthcare Syst, Oral & Maxillofacial Sect, Dent Serv, Los Angeles, CA USA. [Chang, Tina I.] VA Greater Los Angeles Healthcare Syst, Staff Oral & Maxillofacial Surg, Los Angeles, CA USA. [Chang, Tina I.; Friedlander, Arthur H.] Univ Calif Los Angeles, Sch Dent, Los Angeles, CA 90024 USA. [Harada, Nancy D.; Santiago, Silverio M.; Weinreb, Jane E.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Weinreb, Jane E.] Cedar Sinai Med Ctr, Los Angeles, CA USA. [Weinreb, Jane E.] VA Greater Los Angeles Healthcare Syst, Diabet Program, Los Angeles, CA USA. [Friedlander, Arthur H.] Ronald Reagan UCLA Med Ctr, Hosp Dent Serv, Los Angeles, CA USA. RP Friedlander, AH (reprint author), VA Med Ctr, 11301 Wilshire Blvd B218,Rm 210A, Los Angeles, CA 90073 USA. EM arthur.friedlander@med.va.gov NR 84 TC 1 Z9 2 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 0278-2391 J9 J ORAL MAXIL SURG JI J. Oral Maxillofac. Surg. PD JAN PY 2012 VL 70 IS 1 BP 179 EP 187 DI 10.1016/j.joms.2011.01.012 PG 9 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 877WX UT WOS:000299214500046 PM 21601341 ER PT J AU Abramowicz, S Katsnelson, A Forbes, PW Padwa, BL AF Abramowicz, Shelly Katsnelson, Alexander Forbes, Peter W. Padwa, Bonnie L. TI Anterior Versus Posterior Approach to Iliac Crest for Alveolar Cleft Bone Grafting SO JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY LA English DT Article ID LIP NOSE; MORBIDITY; HARVEST; DEFORMITY; RECONSTRUCTION; COMPLICATIONS; AUGMENTATION; TUBERCLE; SITES; ILIUM AB Purpose: The goal of this study was to compare perioperative outcomes for the anterior versus posterior approach to the iliac crest for alveolar bone grafting in patients with cleft lip and palate (CLP). Materials and Methods: A retrospective cohort study of patients with CLP who had an anterior or posterior iliac crest bone graft during a 10-year period was performed. Available medical records were reviewed and the outcome variables documented included the operation site for bone graft procurement (anterior or posterior), estimated blood loss, duration of operation, concurrent procedures, and length of hospital stay. The 2 groups were compared by t test, Fisher exact test, and multivariate regression to show differences. Results: There were 239 patients with CLP who had an iliac crest bone graft to the alveolar cleft; 133 had an anterior and 106 a posterior approach for bone graft procurement. The mean estimated blood loss was significantly less with the posterior approach (85 vs 177 mL; P < .0001). The mean operation duration with the posterior approach was longer (4.6 vs 3.5 hours; P < .0001). Most patients in this group (67%), however, had 2 or more additional procedures during the same anesthetic, whereas only 16% of patients in the anterior group had 2 or more additional procedures. The mean length of stay was significantly shorter for the posterior approach (1.7 vs 2.2 days; P < .0001). Conclusions: These results suggest that patients having a bone graft from the posterior iliac crest have a smaller estimated blood loss and a shorter length of stay. In addition, this approach permits repair of the alveolar cleft and additional procedures, including augmentation of the median tubercle and correction of nasolabial distortions, which are often present in patients with CLP. (C) 2012 American Association of Oral and Maxillofacial Surgeons J Oral Maxillofac Surg 70:211-215, 2012 C1 [Abramowicz, Shelly] Childrens Hosp, Dept Plast & Oral Surg, Boston, MA 02445 USA. [Abramowicz, Shelly; Katsnelson, Alexander; Padwa, Bonnie L.] Harvard Univ, Sch Dent Med, Dept Oral & Maxillofacial Surg, Boston, MA 02115 USA. [Katsnelson, Alexander] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Forbes, Peter W.] Childrens Hosp, Clin Res Program, Boston, MA 02115 USA. [Padwa, Bonnie L.] Childrens Hosp, Sect Oral & Maxillofacial Surg, Boston, MA 02115 USA. RP Abramowicz, S (reprint author), Childrens Hosp, Dept Plast & Oral Surg, 300 Longwood Ave, Boston, MA 02445 USA. EM shelly.abramowicz@childrens.harvard.edu NR 17 TC 7 Z9 7 U1 2 U2 3 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0278-2391 J9 J ORAL MAXIL SURG JI J. Oral Maxillofac. Surg. PD JAN PY 2012 VL 70 IS 1 BP 211 EP 215 DI 10.1016/j.joms.2011.02.044 PG 5 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 877WX UT WOS:000299214500050 PM 21683495 ER PT J AU Lee, A Ghaname, CB Braun, TM Sugai, JV Teles, RP Loesche, WJ Kornman, KS Giannobile, WV Kinney, JS AF Lee, Angie Ghaname, Carrie B. Braun, Thomas M. Sugai, James V. Teles, Ricardo P. Loesche, Walter J. Kornman, Kenneth S. Giannobile, William V. Kinney, Janet S. TI Bacterial and Salivary Biomarkers Predict the Gingival Inflammatory Profile SO JOURNAL OF PERIODONTOLOGY LA English DT Article DE Bacteria; biomarkers; genetic polymorphism; gingivitis; inflammation mediators; saliva ID C-REACTIVE PROTEIN; PERIODONTAL-DISEASE; CREVICULAR FLUID; BACTEROIDES-GINGIVALIS; CLINICAL-PARAMETERS; IL-1 GENOTYPE; PLAQUE; INTERLEUKIN-1-BETA; POLYMORPHISMS; HUMANS AB Background: The aim of this human investigation is to explore the relationship of gingivitis with salivary biomarkers, periodontal pathogens, and interleukin (IL)-1 polymorphism after a transient inflammatory burden. Methods: Thirty healthy human participants were randomized by IL-1 genotype status to control for potential influences of this particular single nucleotide polymorphism on the inflammatory profile. Oral hygiene practices ceased for 21 days to induce gingivitis (induction), after which home care was reinstated until 35 days (resolution). Clinical parameters included plaque (PI) and gingival (GI) indices and papillary bleeding score (PBS). Levels and proportions of 40 subgingival bacteria were determined using checkerboard DNA-DNA hybridization. Saliva was analyzed using a multiplex protein array for 30 biomarkers associated with host defense, inflammation, tissue destruction, and angiogenesis. Results: Mean PI, GI, and PBS values were significantly increased during induction and decreased during resolution as measured at 35 days (P<0.01), although no differences were observed between IL-1 groups. Participants were stratified as either "high" or "low" responders based on inflammatory response (high: GI >1.5; low: GI <= 1.5). Baseline levels of salivary IL-6 and IL-8 demonstrated the highest ability to discriminate between high and low responders (area under the curve [AUC] of 0.81 and 0.72, respectively). Salivary biomarkers, matrix metalloproteinases (MMPs), and bacterial biofilm were combined to generate receiver operating characteristic curves. High levels of IL-6 and MMP-1 at baseline demonstrated the strongest ability to predict high responders (AUC of 0.89; odds ratio of 17.0; 95% confidence interval, 1.7 to 171.7). Conclusion: In this proof-of-concept investigation, we identified specific biomarker and microbial signatures that are associated with gingival inflammation (ClinicalTrials.gov number NCT00980525). J Periodontol 2012;83:79-89. C1 [Kinney, Janet S.] Univ Michigan, Ctr Clin, Michigan Ctr Oral Hlth Res, Dept Periodont & Oral Med, Ann Arbor, MI 48106 USA. [Braun, Thomas M.] Univ Michigan, Sch Publ Hlth, Dept Biostat, Ann Arbor, MI 48106 USA. [Teles, Ricardo P.] Forsyth Inst, Dept Periodontol, Cambridge, MA USA. [Teles, Ricardo P.] Harvard Univ, Sch Dent Med, Div Periodontol, Dept Oral Infect & Immun, Boston, MA 02115 USA. [Loesche, Walter J.] Univ Michigan, Dept Biol & Mat Sci, Sch Dent, Ann Arbor, MI 48109 USA. [Kornman, Kenneth S.] Interleukin Genet, Waltham, MA USA. RP Kinney, JS (reprint author), Univ Michigan, Ctr Clin, Michigan Ctr Oral Hlth Res, Dept Periodont & Oral Med, 24 Frank Lloyd Wright Dr,Box 422, Ann Arbor, MI 48106 USA. EM kinneyj@umich.edu OI Giannobile, William/0000-0002-7102-9746 FU Colgate-Palmolive Company (Piscataway, NJ) [N011792-0]; Michigan Institute for Clinical Health Research [U026020]; National Institutes of Health/National Center for Research Resources [UL1RR024986] FX This work was supported by Colgate-Palmolive Company (Piscataway, NJ) Grant N011792-0, the Michigan Institute for Clinical Health Research (U026020), and National Institutes of Health/National Center for Research Resources Grant UL1RR024986 (J.S. Kinney). This trial was registered in the ClinicalTrials.gov database (identifier no. NCT00980525). The authors thank Lea Franco, Christina Huffman, Alice Liu, Amy Litch, Sooyeon Kwon, Anna Galloro, Chris Jung, and Andrei Taut at the Michigan Center for Oral Health Research, Ann Arbor, Michigan. Dr. Giannobile holds intellectual property related to the diagnostics technology described in this article. Dr. Kornman is chief scientific officer at Interleukin Genetics. Drs. Lee, Ghaname, Braun, Sugai, Teles, and Loesche report no conflicts of interest related to this study. NR 51 TC 24 Z9 24 U1 1 U2 14 PU AMER ACAD PERIODONTOLOGY PI CHICAGO PA 737 NORTH MICHIGAN AVENUE, SUITE 800, CHICAGO, IL 60611-2690 USA SN 0022-3492 J9 J PERIODONTOL JI J. Periodont. PD JAN PY 2012 VL 83 IS 1 BP 79 EP 89 DI 10.1902/jop.2011.110060 PG 11 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 886NT UT WOS:000299861800013 PM 21563952 ER PT J AU Loboprabhu, S Molinari, V AF Loboprabhu, Sheila Molinari, Victor TI Severe Loneliness in Community-Dwelling Aging Adults with Mental Illness SO JOURNAL OF PSYCHIATRIC PRACTICE LA English DT Article DE loneliness; attachment; aging; community; depression ID SOCIAL-ISOLATION; OLDER-PEOPLE; LATER LIFE; SUICIDE; PERSPECTIVES AB Successful aging involves adapting to changing needs. The 2009 U.S. Census noted that 43% of adult Americans are single and that the oldest-old population is the most rapidly growing aging segment. Geriatric, lonely, hopeless individuals are at high risk for depression and suicide. Lonely individuals fail to adapt to their circumstances; and physical and mental illness place them at risk for neglect, morbidity, and mortality. The authors discuss the role of attachment in the individual's subjective experience of loneliness and suggest how attachment theory can be used to guide interventions to improve the individual's self-esteem, coping, and problem-solving abilities. This article also discusses the use of multimodal therapy, including psychodynamic, interpersonal, and cognitive-behavior therapy and coping skills training, to improve the individual's ability to adapt to the surrounding environment and to reintegrate into the community. (Journal of Psychiatric Practice 2012;18:20-28) C1 [Loboprabhu, Sheila] Michael E DeBakey Dept Vet Affairs Med Ctr, Houston, TX 77030 USA. [Loboprabhu, Sheila] S Cent MIRECC, Houston, TX USA. [Loboprabhu, Sheila] Baylor Coll Med, Houston, TX 77030 USA. [Molinari, Victor] Univ S Florida, Tampa, FL USA. RP Loboprabhu, S (reprint author), Michael E DeBakey Dept Vet Affairs Med Ctr, 2002 Holcombe Blvd, Houston, TX 77030 USA. EM SheilaM.Loboprabhu@va.gov NR 45 TC 1 Z9 1 U1 3 U2 17 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1527-4160 J9 J PSYCHIATR PRACT JI J. Psychiatr. Pract. PD JAN PY 2012 VL 18 IS 1 BP 20 EP 28 DI 10.1097/01.pra.0000410984.15852.59 PG 9 WC Psychiatry SC Psychiatry GA 883XP UT WOS:000299668500004 PM 22261980 ER PT J AU Cirnigliaro, CM Lesser, M Moyer, J Kirshblum, SC Bauman, WA Spungen, AM AF Cirnigliaro, Christopher M. Lesser, Marvin Moyer, Jeremy Kirshblum, Steven C. Bauman, William A. Spungen, Ann M. TI Reproducibility and effect of posture on impulse oscillation parameters in persons with spinal cord injury SO JOURNAL OF SPINAL CORD MEDICINE LA English DT Article DE Spinal cord injuries; Paraplegia; Tetraplegia; Forced oscillation technique; Airway dynamics; Respiratory resistance; Airway obstruction; Spirometry; Plethysmography ID RESPIRATORY IMPEDANCE; FORCED OSCILLATION; LUNG; RESISTANCE; MECHANICS; PLETHYSMOGRAPHY; OSCILLOMETRY; QUADRIPLEGIA; SPIROMETRY; OBESITY AB Background: The impulse oscillation system (IOS) offers significant value in the assessment of airway dynamics in persons with spinal cord injury (SCI) because of minimal patient effort but measurement reproducibility in SCI is unknown. Objective: To evaluate between-day reproducibility and the effect of posture on airway resistance [respiratory resistances at 5 Hz (R5) and 20 Hz (R20)] in subjects with tetraplegia, paraplegia and able-bodied controls. Methods: Ten subjects with tetraplegia, 10 subjects with paraplegia and 11 able-bodied individuals were evaluated using IOS. Three 30 second trials were obtained in each while in the seated and supine position on Day 1, and repeated on Day 2. Results: The within-day coefficient of variation (CV%) for R5 and R20 were comparable in the 3 study groups in the seated and supine positions. Compared to controls, the between-day CV% for the combined data was higher in subjects with tetraplegia and paraplegia for R5 seated, and was higher in subjects with tetraplegia for R5 supine. Conclusions: IOS has applicability to the study of within-day respiratory resistance in SCI. However, performing longer-term studies in subjects with tetraplegia and paraplegia may be problematic because of the greater variability for R5 when compared to able-bodied individuals. C1 [Cirnigliaro, Christopher M.; Kirshblum, Steven C.] VA Ctr Excellence Med Consequences SCI, Kessler Inst Rehabil, W Orange, NJ 07052 USA. [Cirnigliaro, Christopher M.; Lesser, Marvin; Moyer, Jeremy; Bauman, William A.; Spungen, Ann M.] James J Peters VA Med Ctr, Rehabil Res & Dev Ctr Excellence Med Consequences, Bronx, NY USA. [Lesser, Marvin; Bauman, William A.; Spungen, Ann M.] James J Peters VA Med Ctr, Med & Spinal Cord Injury Serv, Bronx, NY USA. [Lesser, Marvin; Bauman, William A.; Spungen, Ann M.] Mt Sinai Sch Med, Dept Med, New York, NY USA. [Lesser, Marvin; Bauman, William A.; Spungen, Ann M.] Mt Sinai Sch Med, Dept Rehabil Med, New York, NY USA. [Kirshblum, Steven C.] Univ Med & Dent New Jersey, Dept Phys Med & Rehabil, Newark, NJ 07103 USA. RP Cirnigliaro, CM (reprint author), VA Ctr Excellence Med Consequences SCI, Kessler Inst Rehabil, Room L052m,1199 Pleasant Valley Way, W Orange, NJ 07052 USA. EM christopher.cirnigliaro@va.gov FU James J. Peters Medical Center, Bronx, NY; Department of Veterans Affairs Rehabilitation Research and Development Service; Kessler Institute for Rehabilitation; United Spinal Association [208] FX The authors thank The James J. Peters Medical Center, Bronx, NY, The Department of Veterans Affairs Rehabilitation Research and Development Service, and Kessler Institute for Rehabilitation for their support. This work was funded by a clinical SCI Grant (#208) from United Spinal Association. NR 25 TC 0 Z9 0 U1 0 U2 1 PU MANEY PUBLISHING PI LEEDS PA STE 1C, JOSEPHS WELL, HANOVER WALK, LEEDS LS3 1AB, W YORKS, ENGLAND SN 1079-0268 J9 J SPINAL CORD MED JI J. Spinal Cord. Med. PD JAN PY 2012 VL 35 IS 1 BP 28 EP 34 DI 10.1179/2045772311Y.0000000047 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA 879PX UT WOS:000299345200005 PM 22330188 ER PT J AU Kumar, N Busarla, SVP Sayed, S Kirimi, JM Okiro, P Gakinya, SM Moloo, Z Sohani, AR AF Kumar, Neeta Busarla, Satya Vara Prasad Sayed, Shahin Kirimi, Jesca Muthoni Okiro, Patricia Gakinya, Samuel Mukono Moloo, Zahir Sohani, Aliyah R. TI Telecytology in East Africa: a feasibility study of forty cases using a static imaging system SO JOURNAL OF TELEMEDICINE AND TELECARE LA English DT Article ID TELEMEDICINE PLATFORM; DEVELOPING-WORLD; CYTOLOGY; TELEPATHOLOGY; REPRODUCIBILITY; CONCORDANCE; DIAGNOSIS; PATHOLOGY; ACCURACY; INTERNET AB We conducted a pilot study to assess the feasibility of telecytology as a diagnostic tool in difficult cases originating from a hospital in East Africa. Forty cytology cases considered difficult by a referring pathologist were posted on a telepathology website. Six pathologists independently assessed the static images. Telecytology diagnoses were compared with the consensus diagnoses made on glass slides and also with the histogical diagnoses when available. The diagnostic agreement of the six pathologists was 71-93% and tended to be higher for pathologists with more experience. Reasons for discordance included poor image quality, presence of diagnostic cells in thick areas of smears, sampling bias and screening errors. The consensus diagnoses agreed with histological diagnoses in all 17 cases in which a biopsy was performed. Diagnostic accuracy rates (i.e. telecytology diagnosis vs. histological diagnosis) for individual pathologists were 65-88%. To ensure diagnostic accuracy both referring and consulting pathologists must have adequate training in cytology, image acquisition and image-based diagnosis and the diagnostic questions of importance must be clearly communicated by the referring pathologist when posting a case. C1 [Sohani, Aliyah R.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Sohani, Aliyah R.] Harvard Univ, Sch Med, Boston, MA USA. [Kumar, Neeta; Sayed, Shahin; Gakinya, Samuel Mukono; Moloo, Zahir] Aga Khan Univ Hosp, Dept Pathol, Nairobi, Kenya. [Busarla, Satya Vara Prasad] Aga Khan Hosp, Dept Pathol, Kisumu, Kenya. [Kirimi, Jesca Muthoni] Aga Khan Hosp, Dept Pathol, Dar Es Salaam, Tanzania. [Okiro, Patricia] Aga Khan Hosp, Dept Pathol, Mombasa, Kenya. RP Sohani, AR (reprint author), Massachusetts Gen Hosp, Dept Pathol, 55 Fruit St,WRN 219, Boston, MA 02114 USA. EM arsohani@partners.org OI Sayed, Shahin/0000-0002-3472-511X NR 33 TC 6 Z9 6 U1 0 U2 0 PU ROYAL SOC MEDICINE PRESS LTD PI LONDON PA 1 WIMPOLE STREET, LONDON W1G 0AE, ENGLAND SN 1357-633X J9 J TELEMED TELECARE JI J. Telemed. Telecare PY 2012 VL 18 IS 1 BP 7 EP 12 DI 10.1258/jtt.2011.110308 PG 6 WC Health Care Sciences & Services SC Health Care Sciences & Services GA 886PG UT WOS:000299865700002 PM 22052967 ER PT J AU Konrad-Martin, D Dille, MF McMillan, G Griest, S McDermott, D Fausti, SA Austin, DF AF Konrad-Martin, Dawn Dille, Marilyn F. McMillan, Garnett Griest, Susan McDermott, Daniel Fausti, Stephen A. Austin, Donald F. TI Age-Related Changes in the Auditory Brainstem Response SO JOURNAL OF THE AMERICAN ACADEMY OF AUDIOLOGY LA English DT Article DE Aging; auditory brainstem response; auditory nerve; hearing loss; veterans ID DIABETES-RELATED CHANGES; WAVE-V LATENCY; EVOKED-POTENTIALS; HEARING-LOSS; NERVE ACTIVITY; SEX; CARBOPLATIN; MODEL; ABR; THRESHOLDS AB Purpose: This cross-sectional study had two goals: (1) Identify and quantify the effects of aging on the auditory brainstem response (ABR); (2) Describe how click rate and hearing impairment modify effects of aging. Research Design and Analysis: ABR measures were obtained from 131 predominately male Veteran participants aged 26 to 71 yr. Metrics analyzed include amplitude and latency for waves I, Ill, and V, and the I V interpeak latency interval (IPI) at three repetition rates (11, 51, and 71 clicks/sec) using both polarities. In order to avoid confounding from missing data due to hearing impairment, participants had hearing thresholds <40 dB HL at 2 kHz and 70 dB HL at 4 kHz in at least one ear. Additionally, the median 2, 3, and 4 kHz pure tone threshold average (PTA(2,3,4)) for the sample, similar to 17 dB HL, was used to delineate subgroups of better and worse hearing ears, and only the better hearing sample was modeled statistically. We modeled ABR responses using age, repetition rate, and PTA(2,3,4) as covariates. Random effects were used to model correlation between the two ears of a subject and across repetition rates. Inferences regarding effects of aging on ABR measures at each rate were derived from the fitted model. Results were compared to data from subjects with poorer hearing. Results: Aging substantially diminished amplitudes of all of the principal ABR peaks, largely independent of any threshold differences within the group. For waves I and III, age-related amplitude decrements were greatest at a low (11/sec) click rate. At the 11/sec rate, the model-based mean wave III amplitude was significantly smaller in older compared with younger subjects even after adjusting for wave I amplitude. Aging also increased ABR peak latencies, with significant shifts limited to early waves. The I-V IPI did not change with age. For both younger and older subjects, increasing click presentation rate significantly decreased amplitudes of early peaks and prolonged latencies of later peaks, resulting in increased IPIs. Advanced age did not enhance effects of rate. Instead, the rate effect on wave I and III amplitudes was attenuated for the older subjects due to reduced peak amplitudes at lower click rates. Compared with model predictions from the sample of better hearing subjects, mean ABR amplitudes were diminished in the group with poorer hearing, and wave V latencies were prolonged. Conclusions: In a sample of veterans, aging substantially reduced amplitudes of all principal ABR peaks, with significant latency shifts limited to waves 1 and III. Aging did not influence the I V IPI even at high click rates, suggesting that the observed absolute latency changes associated with aging can be attributed to changes in auditory nerve input. In contrast, ABR amplitude changes with age are not adequately explained by changes in wave I. Results suggest that aging reduces the numbers and/or synchrony of contributing auditory nerve units. Results also support the concept that aging reduces the numbers, though perhaps not the synchrony, of central ABR generators. C1 [Konrad-Martin, Dawn; Dille, Marilyn F.; McMillan, Garnett; Griest, Susan; McDermott, Daniel; Fausti, Stephen A.; Austin, Donald F.] Portland VA Med Ctr, VA RR&D Natl Ctr Rehabilitat Auditory Res, Portland, OR USA. [Konrad-Martin, Dawn; Griest, Susan] Oregon Hlth & Sci Univ, Sch Med, Dept Otolaryngol Head & Neck Surg, Portland, OR 97201 USA. [Austin, Donald F.] Oregon Hlth & Sci Univ, Sch Med, Dept Publ Hlth & Prevent Med, Portland, OR 97201 USA. RP Konrad-Martin, D (reprint author), NCRAR, 3710 SW US Vet Hosp Rd, Portland, OR 97239 USA. EM dawn.martin@va.gov FU National Institutes of Health (NIH), National Institute on Deafness and Other Communication Disorders (NIDCD) [R03 DC008203]; Office of Rehabilitation Research and Development Service (RR&D), Department of Veterans Affairs [C4447K, C3446R] FX This work was supported by grants from the National Institutes of Health (NIH), National Institute on Deafness and Other Communication Disorders (NIDCD) (Grant R03 DC008203 awarded to the first author), and the Office of Rehabilitation Research and Development Service (RR&D), Department of Veterans Affairs (grant C4447K awarded to the first author and C3446R awarded to the last author for the parent study on diabetes mellitus). NR 42 TC 30 Z9 35 U1 0 U2 21 PU AMER ACAD AUDIOLOGY PI RESTON PA 11730 PLAZA DR, STE 300, RESTON, VA 20190 USA SN 1050-0545 J9 J AM ACAD AUDIOL JI J. Am. Acad. Audiol. PD JAN PY 2012 VL 23 IS 1 BP 18 EP 35 DI 10.3766/jaaa.23.1.3 PG 18 WC Audiology & Speech-Language Pathology; Otorhinolaryngology SC Audiology & Speech-Language Pathology; Otorhinolaryngology GA 883QV UT WOS:000299649700003 PM 22284838 ER PT J AU Jones, EG El-Zawahry, AM AF Jones, Elizabeth Geiger El-Zawahry, Ahmed M. TI Curative Treatment Without Surgical ReconstructionaAftr Perineal Debridement of Fournier's Gangrene SO JOURNAL OF WOUND OSTOMY AND CONTINENCE NURSING LA English DT Article ID HYPERBARIC-OXYGEN; MANAGEMENT; THERAPY AB BACKGROUND: Fournier's gangrene (necrotizing fasciitis) is an acute life-threatening disease of the perineal area that requires urgent medical intervention. Once the affected area is surgically debrided and the patient is stabilized, surgical management typically involves 1 or more additional procedures that may include split-thickness skin grafts, flaps, or an elective diverting urostomy and/or colostomy. The professional literature discussing nonsurgical approaches to healing for Fournier's gangrene after surgical debridement is sparse. CASE: We present 3 cases of male patients with Fournier's gangrene from our facility who healed uneventfully with negative pressure wound therapy placed after extensive debridement without further surgical intervention. An added benefit was a satisfactory aesthetic effect. CONCLUSION: Expert wound management including negative pressure wound therapy after surgical debridement of Fournier's gangrene eliminated the need for further operative procedures and prolonged hospitalizations in these cases. We believe that surgical teams should consider using negative pressure wound therapy as part of the initial curative plan of care after debridement, and that plans for restorative plastic surgery should be restricted to patients who do not exhibit adequate improvement with conservative wound management. C1 [El-Zawahry, Ahmed M.] Med Univ S Carolina, Charleston, SC USA. [El-Zawahry, Ahmed M.] Ralph H Johnson VA Med Ctr, Dept Urol, Charleston, SC 29401 USA. EM Gwammyliz@heavi.tv NR 15 TC 2 Z9 2 U1 2 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1071-5754 J9 J WOUND OSTOMY CONT JI J. Wound Ostomy Cont. Nurs. PD JAN-FEB PY 2012 VL 39 IS 1 BP 98 EP 102 DI 10.1097/WON.0b013e31823fe212 PG 5 WC Nursing SC Nursing GA 881OY UT WOS:000299497200012 PM 22237647 ER PT J AU Joyce, VR Barnett, PG Chow, A Bayoumi, AM Griffin, SC Sun, HY Holodniy, M Brown, ST Kyriakides, TC Cameron, DW Youle, M Sculpher, M Anis, AH Owens, DK AF Joyce, Vilija R. Barnett, Paul G. Chow, Adam Bayoumi, Ahmed M. Griffin, Susan C. Sun, Huiying Holodniy, Mark Brown, Sheldon T. Kyriakides, Tassos C. Cameron, D. William Youle, Mike Sculpher, Mark Anis, Aslam H. Owens, Douglas K. TI Effect of Treatment Interruption and Intensification of Antiretroviral Therapy on Health-Related Quality of Life in Patients with Advanced HIV: A Randomized, Controlled Trial SO MEDICAL DECISION MAKING LA English DT Article DE AIDS; HIV; highly active antiretroviral therapy; quality of life; treatment interruption; treatment intensification; randomized trial ID HUMAN-IMMUNODEFICIENCY-VIRUS; CD4 CELL COUNTS; STRUCTURED TREATMENT INTERRUPTIONS; INFECTED PATIENTS; HIV-1-INFECTED PATIENTS; DRUG-RESISTANCE; VIROLOGICAL FAILURE; CUBIC MILLIMETER; UTILITY SCORES; CLINICAL-TRIAL AB Background. The effect of antiretroviral therapy (ART) interruption or intensification on health-related quality of life (HRQoL) in advanced HIV patients is unknown. Objective. To assess the impact of temporary treatment interruption and intensification of ART on HRQoL. Design. A 2 x 2 factorial open label randomized controlled trial. Setting. Hospitals in the United States, Canada, and the United Kingdom. Patients. Multidrug resistant (MDR) HIV patients. Intervention. Patients were randomized to receive a 12-wk interruption or not, and ART intensification or standard ART. Measurements. The Health Utilities Index (HUI3), EQ-5D, standard gamble (SG), time tradeoff (TTO), visual analog scale (VAS), and the Medical Outcomes Study HIV Health Survey (MOS-HIV). Results. There were no significant differences in HRQoL among the four groups during follow-up; however, there was a temporary significant decline in HRQoL on some measures within the interruption group during interruption (HUI3 -0.05, P = 0.03; VAS -5.9, P = 0.002; physical health summary -2.9, P = 0.001; mental health summary -1.9, P = 0.02). Scores declined slightly overall during follow-up. Multivariate analysis showed significantly lower HRQoL associated with some clinical events. Limitations. The results may not apply to HIV patients who have not experienced multiple treatment failures or who have not developed MDR HIV. Conclusions. Temporary ART interruption and ART intensification provided neither superior nor inferior HRQoL compared with no interruption and standard ART. Among surviving patients, HRQoL scores declined only slightly over years of follow-up in this advanced HIV cohort; however, approximately one-third of patients died during the trial follow up. Lower HRQoL was associated with adverse clinical events. C1 [Joyce, Vilija R.; Barnett, Paul G.; Chow, Adam] VA Palo Alto Hlth Care Syst, VA Cooperat Studies Program Coordinating Ctr, VA HSR&D Hlth Econ Resource Ctr, Menlo Pk, CA 94025 USA. [Bayoumi, Ahmed M.] St Michaels Hosp, Li Ka Shing Knowledge Inst, Keenan Res Ctr, Ctr Res Inner City Hlth, Toronto, ON M5B 1W8, Canada. [Bayoumi, Ahmed M.] St Michaels Hosp, Div Gen Internal Med, Toronto, ON M5B 1W8, Canada. [Bayoumi, Ahmed M.] Univ Toronto, Dept Med, Toronto, ON M5S 1A1, Canada. [Bayoumi, Ahmed M.] Univ Toronto, Dept Hlth Policy Management & Evaluat, Toronto, ON M5S 1A1, Canada. [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; Anis, Aslam H.] Canadian HIV Trials Network, Vancouver, BC, Canada. [Holodniy, Mark; Owens, Douglas K.] VA Palo Alto Hlth Care Syst, Palo Alto, CA USA. [Brown, Sheldon T.] James J Peters VA Med Ctr, Bronx, NY USA. [Kyriakides, Tassos C.] VA Cooperat Studies Program Coordinating Ctr, West Haven, CT USA. [Cameron, D. William] Univ Ottawa, Ottawa Hosp Res Inst, Div Infect Dis, Ottawa, ON, Canada. [Youle, Mike] Royal Free Hosp, London NW3 2QG, England. [Anis, Aslam H.] Univ British Columbia, Dept Hlth Care & Epidemiol, Vancouver, BC V6T 1W5, Canada. [Owens, Douglas K.] Stanford Univ, Ctr Primary Care & Outcomes Res, Stanford, CA 94305 USA. RP Joyce, VR (reprint author), VA Palo Alto Hlth Care Syst, Hlth Econ Resource Ctr, 795 Willow Rd,152 MPD, Menlo Pk, CA 94025 USA. EM vilija.joyce@va.gov RI Joyce, Vilija/A-2578-2013; OI Joyce, Vilija/0000-0002-2484-4625; Cameron, Bill/0000-0002-0090-3539 FU Ontario HIV Treatment Network, Ontario Ministry of Health; Department of Veterans Affairs; Veterans Health Administration; Office of Research and Development; UK Medical Research Council; Canadian Institutes for Health Research; United Kingdom Medical Research Council FX Dr. Cameron is supported by a Career Scientist Award of the Ontario HIV Treatment Network, Ontario Ministry of Health. We thank the investigators and staff at the participating sites. We also thank Dr. Diane Fairclough for her expertise in missing data analysis techniques and longitudinal modeling.; Received 14 July 2010 from the VA Palo Alto Health Care System, VA Cooperative Studies Program Coordinating Center, VA HSR&D Health Economics Resource Center, Menlo Park, California (VRJ, PGB, AC); Centre for Research on Inner City Health, The Keenan Research Centre in the Li Ka Shing Knowledge Institute and Division of General Internal Medicine, St. Michael's Hospital, Toronto, Ontario, Canada and Departments of Medicine and Health Policy, Management and Evaluation, University of Toronto, Ontario, Canada (AMB); Centre for Health Economics, University of York, York, United Kingdom (SCG, MS); Centre for Health Evaluation and Outcome Sciences, St. Paul's Hospital, Vancouver, British Columbia, Canada (HS); Canadian HIV Trials Network, Vancouver, British Columbia, Canada (HS, AHA); VA Palo Alto Health Care System, Palo Alto, California (MH, DKO); James J. Peters VA Medical Center, Bronx, New York (STB); VA Cooperative Studies Program Coordinating Center, West Haven, Connecticut (TCK); Division of Infectious Diseases, University of Ottawa at the Ottawa Hospital Research Institute, Ottawa, Ontario, Canada (DWC); Royal Free Hospital, London, United Kingdom (MY); Department of Health Care and Epidemiology, University of British Columbia, Vancouver, British Columbia, Canada (AHA); and Center for Primary Care and Outcomes Research, Stanford University, Stanford, California (DKO). Earlier versions of this work were presented at the Canadian Association for HIV Research Conference, Vancouver, Canada, April 2009 and at the Society for Medical Decision Making Annual Meeting, Los Angeles, California, October 2009. This material is based on work supported by the Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Cooperative Studies Program; the UK Medical Research Council; and the Canadian Institutes for Health Research. Options in Management with Antiretrovirals is the initial trial of the newly established trinational program involving the above 3 agencies. 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. Primary funding source: Department of Veterans Affairs Cooperative Studies Program, the United Kingdom Medical Research Council, and the Canadian Institutes for Health Research. Trial registration: http://clinicaltrials.gov, No. NCT00050089. Revision accepted for publication 8 December 2010. NR 50 TC 4 Z9 4 U1 1 U2 3 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0272-989X J9 MED DECIS MAKING JI Med. Decis. Mak. PD JAN-FEB PY 2012 VL 32 IS 1 BP 70 EP 82 DI 10.1177/0272989X10397615 PG 13 WC Health Care Sciences & Services; Medical Informatics SC Health Care Sciences & Services; Medical Informatics GA 884JN UT WOS:000299701100011 PM 21383086 ER PT J AU Krop, I AF Krop, Ian TI Improving Therapy for HER2-Positive Cancers Through Neoadjuvant Studies SO ONCOLOGY-NEW YORK LA English DT Editorial Material ID OPERABLE BREAST-CANCER; CHEMOTHERAPY; TRASTUZUMAB; REGIMEN; UPDATE; TRIAL C1 Dana Farber Canc Inst, Boston, MA 02115 USA. RP Krop, I (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. NR 10 TC 0 Z9 0 U1 0 U2 0 PU UBM MEDICA PI NORWALK PA 535 CONNECTICUT AVE, STE 300, NORWALK, CT 06854 USA SN 0890-9091 J9 ONCOLOGY-NY JI Oncology-NY PD JAN PY 2012 VL 26 IS 1 BP 34 EP + PG 2 WC Oncology SC Oncology GA 883UB UT WOS:000299659300004 PM 22393794 ER PT J AU Manchikanti, L Benyamin, RM Falco, FJE Caraway, DL Datta, S Hirsch, JA AF Manchikanti, Laxmaiah Benyamin, Ramsin M. Falco, Frank J. E. Caraway, David L. Datta, Sukdeb Hirsch, Joshua A. TI Guidelines Warfare Over Interventional Techniques: Is There a Lack of Discourse or Straw Man? SO PAIN PHYSICIAN LA English DT Review DE Guidelines; interventional pain management; professionalism; discourse; disclosure; conflicts of interest; evidence-based medicine; comparative effectiveness research; Patient-Centered Outcomes Research Institute ID LOW-BACK-PAIN; EVIDENCE-BASED-MEDICINE; SERVICES-TASK-FORCE; CLINICAL-PRACTICE GUIDELINES; CAUDAL EPIDURAL INJECTIONS; MEDIAL BRANCH BLOCKS; FACET JOINT PAIN; CHRONIC NONCANCER PAIN; CHRONIC SPINAL PAIN; DOUBLE-BLIND TRIAL AB Guideline development seems to have lost some of its grounding as a medical science. At their best, guidelines should be a constructive response to assist practicing physicians in applying the exponentially expanding body of medical knowledge. In fact, guideline development seems to be evolving into a cottage industry with multiple, frequently discordant guidance on the same subject. Evidence Based Medicine does not always provide for conclusive opinions. With competing interests of payers, practitioners, health policy makers, and third parties benefiting from development of the guidelines as cost saving measures, guideline preparation has been described as based on pre-possession, vagary, rationalization, or congeniality of conclusion. Beyond legitimate differences in opinions regarding the evidence that could yield different guidelines there are potentials for conflicts of interest and various other issues play a major role in guideline development. As is always the case, conflicts of interest in guideline preparation must be evaluated and considered. Following the development of American Pain Society (APS) guidelines there has been an uproar in interventional pain management communities on various issues related to not only the evidence synthesis, but conflicts of interest. A recent manuscript published by Chou et al, in addition to previous publications appear to have limited clinician involvement in the development of APS guidelines, demonstrates some of these challenges clearly. This manuscript illustrates the deficiencies of Chou et al's criticisms, and demonstrates their significant conflicts of interest, and use a lack of appropriate evaluations in interventional pain management as a straw man to support their argument. Further, this review will attempt to demonstrate that excessive focus on this straw man has inhibited critique of what we believe to be flaws in the approach. C1 [Manchikanti, Laxmaiah] Pain Management Ctr Paducah, Paducah, KY USA. [Manchikanti, Laxmaiah] Univ Louisville, Louisville, KY 40292 USA. [Benyamin, Ramsin M.] Millennium Pain Ctr, Bloomington, IL USA. [Falco, Frank J. E.] Mid Atlantic Spine & Pain Phys Newark, Newark, DE USA. [Falco, Frank J. E.] Temple Univ Hosp & Med Sch, Philadelphia, PA 19140 USA. [Caraway, David L.] St Marys Pain Relief Ctr, Huntington, WV USA. [Datta, Sukdeb] Laser Spine & Pain Inst, New York, NY USA. [Hirsch, Joshua A.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Hirsch, Joshua A.] Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. [Hirsch, Joshua A.] Harvard Univ, Sch Med, Boston, MA USA. RP Manchikanti, L (reprint author), 2831 Lone Oak Rd, Paducah, KY 42003 USA. EM drlm@thepainmd.com NR 331 TC 64 Z9 64 U1 0 U2 11 PU AM SOC INTERVENTIONAL PAIN PHYSICIANS PI PADUCAH PA 81 LAKEVIEW DR, PADUCAH, KY 42001 USA SN 1533-3159 J9 PAIN PHYSICIAN JI Pain Physician PD JAN-FEB PY 2012 VL 15 IS 1 BP E1 EP E26 PG 26 WC Anesthesiology; Clinical Neurology SC Anesthesiology; Neurosciences & Neurology GA 885NL UT WOS:000299785600001 PM 22270745 ER PT J AU Manchikanti, L Singh, V Caraway, DL Benyamin, RM Falco, FJE Hirsch, JA AF Manchikanti, Laxmaiah Singh, Vijay Caraway, David L. Benyamin, Ramsin M. Falco, Frank J. E. Hirsch, Joshua A. TI Physician Payment Outlook for 2012: Deja Vu SO PAIN PHYSICIAN LA English DT Review DE Health policy; physician payment policy; physician fee schedule; Medicare; sustained growth rate formula; interventional pain management; regulatory reform ID LOW-BACK-PAIN; EPIDURAL STEROID INJECTIONS; ACTIVE CONTROLLED-TRIAL; CLINICAL-PRACTICE GUIDELINE; FACET JOINT INTERVENTIONS; CHRONIC SPINAL PAIN; 2-YEAR FOLLOW-UP; CONTROLLED DIAGNOSTIC BLOCKS; LUMBAR DISC HERNIATION; CHRONIC THORACIC PAIN AB Physician spending is complex related to national health care spending, government regulations, health care reform, private insurers, physician practice, and patient utilization patterns. In determining payment rates for each service on the fee schedule, the Centers for Medicare and Medicaid Services (CMS) considers the amount of work required to provide a service, expenses related to maintaining a practice, and liability insurance costs. The value of 3 types of resources are adjusted on a yearly basis of the combined total multiplied by a standard dollar amount, called the fee schedules conversion factor, which was $33.98 in 2011, to arrive at the payment amount. This factor will stay almost the same ($34.03) unless a 27.4% cut in the sustainable growth rate (SGR) takes place or CMS enacts further reductions. With a 27.4% cut, the conversion factor will be $24.67 in 2012 after the first 2 months if Congress fails to act. Since the inception of Medicare programs in 1965, several methods have been used to determine the amounts paid to physicians for each covered service. The SGR was enacted in 1997 to determine physician payment updates under Medicare Part B with intent to reduce Medicare physician payment updates to offset the growth and utilization of physician services that exceed gross domestic product (GDP) growth. This is achieved by setting an overall target amount of spending for physicians' services and adjusting payment rates annually to reflect differences between actual spending and the spending target. Since 2002, the SGR has annually recommended reductions in Medicare reimbursements. Payments were cut in 2002 by 4.8%. Since then, Congress has intervened on 13 separate occasions to prevent additional cuts from being imposed. The Medicare physician payment rule of 2012, which is still undergoing revisions -- but considered as the final rule-- is a 1,235 page document, released in November 2011. In this manuscript, we will describe important aspects of the 2012 physician fee schedule which include potentially disvalued services under the physician fee schedule, expansion of the multiple procedure payment reduction (MPPR) policy, establishment of the value-based payment modifier, changes to direct practice expenses (PEs), electronic prescribing, the Physician Quality Reporting System (PQRS), and lab testing signatures, along with their implications. Additionally, the impact of multiple changes on interventional pain management will be described. In conclusion, interventional pain management is facing widespread challenges in the U. S. health care system. A historic reform, which has been passed by Congress and signed into law, whose survivability is not quite known yet, is affecting medicine drastically in the United States. Interventional pain management, like other evolving specialties, will probably most likely suffer under the new affordable health care law and regulatory burden. C1 [Manchikanti, Laxmaiah] Pain Management Ctr Paducah, Paducah, KY USA. [Manchikanti, Laxmaiah] Univ Louisville, Louisville, KY 40292 USA. [Singh, Vijay] Pain Diagnost Associates, Niagara, WI USA. [Caraway, David L.] St Marys Pain Relief Ctr, Huntington, WV USA. [Benyamin, Ramsin M.] Millennium Pain Ctr, Bloomington, IL USA. [Falco, Frank J. E.] Mid Atlantic Spine & Pain Phys Newark, Newark, DE USA. [Falco, Frank J. E.] Temple Univ Hosp & Med Sch, Philadelphia, PA 19140 USA. [Hirsch, Joshua A.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Hirsch, Joshua A.] Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. [Hirsch, Joshua A.] Harvard Univ, Sch Med, Boston, MA USA. RP Manchikanti, L (reprint author), 2831 Lone Oak Rd, Paducah, KY 42003 USA. EM drlm@thepainmd.com NR 130 TC 9 Z9 9 U1 2 U2 7 PU AM SOC INTERVENTIONAL PAIN PHYSICIANS PI PADUCAH PA 81 LAKEVIEW DR, PADUCAH, KY 42001 USA SN 1533-3159 J9 PAIN PHYSICIAN JI Pain Physician PD JAN-FEB PY 2012 VL 15 IS 1 BP E27 EP E52 PG 26 WC Anesthesiology; Clinical Neurology SC Anesthesiology; Neurosciences & Neurology GA 885NL UT WOS:000299785600002 PM 22270747 ER PT J AU Singh, JA Kundukulam, JA Bhandari, M AF Singh, Jasvinder A. Kundukulam, Joseph A. Bhandari, Mohit TI A systematic review of validated methods for identifying orthopedic implant removal and revision using administrative data SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Review DE systematic review; orthopedic implant; implant removal; revision; total hip arthroplasty; arthroplasty ID TOTAL KNEE ARTHROPLASTY; TOTAL HIP-ARTHROPLASTY; STATES MEDICARE POPULATION; TOTAL JOINT ARTHROPLASTY; TOTAL SHOULDER ARTHROPLASTY; TERM COMPLICATION RATES; QUALITY-OF-LIFE; UNITED-STATES; PATIENT OUTCOMES; HOSPITAL VOLUME AB Purpose To identify studies that have validated administrative and claims database algorithms for identifying patients with orthopedic device revision or removal. Methods As a part of the Food and Drug Administration's Mini-Sentinel pilot program, we performed a systematic review to identify algorithms for orthopedic implant removal/ revision in administrative and claims databases in the USA or Canada. Results Five studies examined the validity of database algorithms against a gold standard of documentation in medical records (n = 3) or codes/ documentation in another database (n = 2). The positive predictive values (PPV) of the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) and/or the Current Procedural Terminology codes for revision total hip arthroplasty (THA) in the US Medicare population compared with medical record review were 92% and 91%, respectively. In another study of the US Medicare population, multiple ICD-9 codes for revision total knee arthroplasty were compared with newly available single ICD-9-CM codes for revision knee arthroplasty; sensitivity was 87% and specificity was 99% (PPV not provided). The fourth study validated the ICD-9-CM codes for revision total knee arthroplasty against Ontario health insurance physician fee service claims as the gold standard and found a PPV of 32%. In the last study in Medicare population, the accuracy of the attribution of revision THA to the same side as the earlier index primary THA was examined; PPV for same laterality of revision THA was 71% (using ICD-9-CM codes). Conclusions Validation data, with regard to the ICD-9-CM or the Current Procedural Terminology code algorithms for revision THA in the Medicare population, exist. More validation studies are needed to confirm these findings and examine other large databases. Copyright c (C) 2012 John Wiley & Sons, Ltd. C1 [Singh, Jasvinder A.; Kundukulam, Joseph A.] Univ Alabama, Dept Med, Birmingham, AL 35294 USA. [Singh, Jasvinder A.] Univ Alabama, Div Epidemiol, Sch Publ Hlth, Birmingham, AL 35294 USA. [Singh, Jasvinder A.] Birmingham VA Med Ctr, Med Serv, Birmingham, AL USA. [Singh, Jasvinder A.] Birmingham VA Med Ctr, Ctr Surg Med Acute Care Res & Transit C SMART, Birmingham, AL USA. [Singh, Jasvinder A.] Mayo Clin, Sch Med, Dept Orthoped Surg, Rochester, MN USA. [Bhandari, Mohit] McMaster Univ, Dept Surg, Hamilton, ON L8S 4L8, Canada. RP Singh, JA (reprint author), Univ Alabama, Dept Med, Fac Off Tower 805B,510 20th St S, Birmingham, AL 35294 USA. EM Jasvinder.md@gmail.com OI singh, jasvinder/0000-0003-3485-0006 FU Allergan; Takeda; Savient; Wyeth; Amgen; URL pharmaceuticals; Novartis; Stryker; Smith; Nephew; Zimmer; Pfizer; DePuy; FDA through the Department of Health and Human Services (HHS) [HHSF223200910006I] FX There are no financial conflicts related to this work. J.A.S. has received speaker honoraria from Abbott; research and travel grants from Allergan, Takeda, Savient, Wyeth, and Amgen; and consultant fees from Savient, URL pharmaceuticals, and Novartis. M.B. has received research funding from Stryker, Smith, and Nephew, Zimmer, Pfizer, Amgen, and DePuy. J.A.K. has no financial relationships.; This work was supported by the FDA through the Department of Health and Human Services (HHS) contract number HHSF223200910006I. The study sponsors had no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the manuscript; and in the decision to submit the manuscript for publication. The views expressed in this document do not necessarily reflect the official policies of the Department of Health and Human Services, nor does the mention of trade names, commercial practices, or organizations imply endorsement by the US government. The views expressed in this article are those of the authors and do not necessarily reflect the position or policy of the Department of Veterans Affairs. NR 61 TC 7 Z9 7 U1 1 U2 7 PU WILEY PERIODICALS, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN STREET, MALDEN, MA 02148-529 USA SN 1053-8569 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD JAN PY 2012 VL 21 SU 1 BP 265 EP 273 DI 10.1002/pds.2309 PG 9 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA 878JU UT WOS:000299253900031 PM 22262616 ER PT J AU Uher, R Tansey, KE Malki, K Perlis, RH AF Uher, Rudolf Tansey, Katherine E. Malki, Karim Perlis, Roy H. TI Biomarkers predicting treatment outcome in depression: what is clinically significant? SO PHARMACOGENOMICS LA English DT Article DE antidepressant medication; biomarkers; clinical significance; major depressive disorder; number needed to assess ID STAR-ASTERISK-D; ANTIDEPRESSANT RESPONSE; MONTGOMERY-ASBERG; NORTRIPTYLINE; PSYCHOTHERAPY; METAANALYSIS; ESCITALOPRAM; ASSOCIATION; RATIONALE; SEVERITY AB Aim: To extend to biomarker studies the consensus clinical significance criterion of a three-point difference in Hamilton Rating Scale for Depression. Materials & methods: We simulated datasets modeled on large clinical trials. Results: In a typical clinical trial comparing active treatment and placebo, a difference of three Hamilton Rating Scale for Depression (HRSD) points at the end of treatment corresponds to 6.3% of variance in outcome explained. To achieve a similar explanatory power, genotypes with minor allele frequencies of 5, 10, 20, 30 and 50% need to attain a per allele difference of 4.7, 3.6, 2.8, 2.4 and 2.2 HRSD points, respectively. A normally distributed continuous biomarker will need an effect size of 1.5 HRSD points per standard deviation. A number needed to assess of three suggests that with this effect size, a biomarker will significantly improve the prediction of outcome in one out of every three patients assessed. Conclusion: This report provides guidance on assessing clinical significance of biomarkers predictive of outcome in depression treatment. C1 [Uher, Rudolf; Tansey, Katherine E.; Malki, Karim] Kings Coll London, Inst Psychiat, London SE5 8AF, England. [Uher, Rudolf] Dalhousie Univ, Brain Repair Ctr, Halifax, NS, Canada. [Perlis, Roy H.] Massachusetts Gen Hosp, Dept Psychiat, Lab Psychiat Pharmacogenom, Boston, MA 02114 USA. [Perlis, Roy H.] Harvard Univ, Sch Med, Boston, MA USA. RP Uher, R (reprint author), Kings Coll London, Inst Psychiat, 16 De Crespigny Pk, London SE5 8AF, England. EM rudolf.uher@kcl.ac.uk RI Uher, Rudolf/A-5477-2008; Tansey, Katherine/B-1033-2013 OI Uher, Rudolf/0000-0002-2998-0546; Tansey, Katherine/0000-0002-9663-3376 FU Innovative Medicine Initiative Joint Undertaking (IMI-JU) [115008]; European Federation of Pharmaceutical Industries and Associations (EFPIA); EU [FP7/2007-2013]; National Institute of Mental Health [MH086026]; Proteus Biomedical; Concordant Rater Systems; RIDventures FX The research leading to these results has received support from the Innovative Medicine Initiative Joint Undertaking (IMI-JU) under grant agreement No. 115008, of which, resources are composed of EU and the European Federation of Pharmaceutical Industries and Associations (EFPIA) in-kind contribution and financial contribution from the EU's Seventh Framework Program (FP7/2007-2013). RH Perlis is supported by the National Institute of Mental Health MH086026. R Uher consults for the WHO. RH Perlis has received consulting fees from Proteus Biomedical, Concordant Rater Systems and RIDventures and research finding from National Institute of Mental Health. None of these organizations have direct interest in the content of this publication. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. NR 32 TC 20 Z9 20 U1 0 U2 8 PU FUTURE MEDICINE LTD PI LONDON PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3 1QB, ENGLAND SN 1462-2416 J9 PHARMACOGENOMICS JI Pharmacogenomics PD JAN PY 2012 VL 13 IS 2 BP 233 EP 240 DI 10.2217/PGS.11.161 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 886OP UT WOS:000299864000019 PM 22256872 ER PT J AU Tanaka, M Kinoshita, M Yoshihara, Y Shinomiya, N Seki, S Nemoto, K Hirayama, T Dai, TH Huang, LY Hamblin, MR Morimoto, Y AF Tanaka, Masamitsu Kinoshita, Manabu Yoshihara, Yasuo Shinomiya, Nariyoshi Seki, Shuhji Nemoto, Koichi Hirayama, Takahiro Dai, Tianhong Huang, Liyi Hamblin, Michael R. Morimoto, Yuji TI Optimal Photosensitizers for Photodynamic Therapy of Infections Should Kill Bacteria but Spare Neutrophils SO PHOTOCHEMISTRY AND PHOTOBIOLOGY LA English DT Article ID MURINE MRSA ARTHRITIS; IN-VIVO; STAPHYLOCOCCUS-AUREUS; PHENOTHIAZINIUM DYES; ANTITUMOR IMMUNITY; BASIC PRINCIPLES; METHYLENE-BLUE; HEMATOPORPHYRIN; INACTIVATION; MICROORGANISMS AB Photodynamic therapy (PDT) for localized microbial infections exerts its therapeutic effect both by direct bacterial killing and also by the bactericidal effects of host neutrophils stimulated by PDT. Therefore, PDT-induced damage to neutrophils must be minimized, while direct photoinactivation of bacteria is maintained to maximize the therapeutic efficacy of antimicrobial PDT in vivo. However, there has been no study in which the cytocidal effect of PDT on neutrophils was investigated. In this study, the cytocidal effects of PDT on neutrophils were evaluated using different antimicrobial photosensitizers to find suitable candidate photosensitizers for antimicrobial PDT. PDT on murine peripheral-blood neutrophils was performed in vitro using each photosensitizer at a concentration that exerted a maximum bactericidal effect on methicillin-resistant Staphylococcus aureus, and morphological alteration and viability of neutrophils were studied. Most neutrophils were viable (>80%) after PDT using toluidine blue-O (TB) or methylene blue (MB), while neutrophils showed morphological change and their viabilities were decreased (<70%) after PDT using other photosensitizers (erythrosine B, rose bengal, crystal violet, Photofrin, new methylene blue and Laserphyrin). These results suggest that PDT using TB or MB can preserve host neutrophils while exerting a significant therapeutic effect on in vivo localized microbial infection. C1 [Shinomiya, Nariyoshi; Hirayama, Takahiro; Morimoto, Yuji] Natl Def Med Coll, Dept Integrat Physiol & Bionano Med, Tokorozawa, Saitama 359, Japan. [Tanaka, Masamitsu; Yoshihara, Yasuo; Nemoto, Koichi] Natl Def Med Coll, Dept Orthoped Surg, Tokorozawa, Saitama 359, Japan. [Tanaka, Masamitsu; Dai, Tianhong; Huang, Liyi; Hamblin, Michael R.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Tanaka, Masamitsu; Dai, Tianhong; Huang, Liyi; Hamblin, Michael R.] Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. [Kinoshita, Manabu; Seki, Shuhji] Natl Def Med Coll, Dept Immunol & Microbiol, Tokorozawa, Saitama 359, Japan. [Hamblin, Michael R.] Harvard MIT Div Hlth Sci & Technol, Cambridge, MA USA. RP Morimoto, Y (reprint author), Natl Def Med Coll, Dept Integrat Physiol & Bionano Med, Tokorozawa, Saitama 359, Japan. EM dr21046@ndmc.ac.jp OI Hamblin, Michael/0000-0001-6431-4605 FU Ministry of Education, Culture, Sports, Science and Technology of Japan [23659628]; US NIH [R01AI050875]; Airlift Research Foundation [109421] FX This work was supported by a Grant-in-Aid for Challenging Exploratory Research (23659628) from the Ministry of Education, Culture, Sports, Science and Technology of Japan to Yuji Morimoto. Liyi Huang and Michael R. Hamblin were supported by US NIH grant R01AI050875 to MRH and Tianhong Dai by an Airlift Research Foundation Extremity Trauma Research Grant (grant 109421). NR 33 TC 26 Z9 27 U1 1 U2 21 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0031-8655 J9 PHOTOCHEM PHOTOBIOL JI Photochem. Photobiol. PD JAN-FEB PY 2012 VL 88 IS 1 BP 227 EP 232 DI 10.1111/j.1751-1097.2011.01005.x PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 871LU UT WOS:000298740400030 PM 21950417 ER PT J AU Hoerster, KD Butler, DA Mayer, JA Finlayson, T Gallo, LC AF Hoerster, Katherine D. Butler, Dalila A. Mayer, Joni A. Finlayson, Tracy Gallo, Linda C. TI Use of conventional care and complementary/alternative medicine among US adults with arthritis SO PREVENTIVE MEDICINE LA English DT Article DE Arthritis; Epidemiology; Disparities; Access to care ID ALTERNATIVE MEDICINE; ACTIVITY LIMITATIONS; IMPACT AB Objective: Managing arthritis and co-morbid conditions is of public health importance. It is therefore critical to have a comprehensive understanding of healthcare utilization among US adults with arthritis. Thus, the present study identified characteristics associated with using both complementary and alternative medicine (CAM) and conventional healthcare. Method: Using 2007 National Health Interview Survey data, multinomial logistic regression was performed to compare four categories of past year healthcare use (both CAM and conventional care vs. conventional care only, CAM only, and no healthcare use) on their potential correlates. Results: The sample (n = 3850) was 62.8% female and 80.4% non-Hispanic White. Nearly half were at least 65 years old, and had used both CAM and conventional services in the previous year. The following characteristics were associated with having used neither CAM nor conventional care in the previous year (vs. having used both CAM and conventional care): being from an ethnic and racial minority group (ORs = 2.44. 3.26, and 3.91) and being uninsured (OR = 4.06), identifying individuals potentially at risk for unmet need. Conclusion: To ensure access to comprehensive care, potentially underserved populations should be targeted with outreach (e.g., providing low-cost, accessible care, and education about benefits of various treatments for arthritis and co-morbid conditions). Published by Elsevier Inc. C1 [Hoerster, Katherine D.; Butler, Dalila A.; Mayer, Joni A.; Finlayson, Tracy] San Diego State Univ, Grad Sch Publ Hlth, San Diego, CA 92123 USA. [Hoerster, Katherine D.; Gallo, Linda C.] Univ Calif San Diego, San Diego State Univ, San Diego Joint Doctoral Program Clin Psychol, San Diego, CA 92120 USA. San Diego State Univ, Dept Psychol, San Diego, CA 92182 USA. RP Hoerster, KD (reprint author), VA Puget Sound Healthcare Syst, Seattle Div, 1660 S Columbian Way S-116, Seattle, WA 98108 USA. EM Katherine.Hoerster@va.gov NR 14 TC 6 Z9 6 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0091-7435 J9 PREV MED JI Prev. Med. PD JAN 1 PY 2012 VL 54 IS 1 BP 13 EP 17 DI 10.1016/j.ypmed.2011.08.023 PG 5 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA 881BM UT WOS:000299455500005 PM 21889528 ER PT J AU Milad, MR Rauch, SL AF Milad, Mohammed R. Rauch, Scott L. TI Obsessive-compulsive disorder: beyond segregated cortico-striatal pathways SO TRENDS IN COGNITIVE SCIENCES LA English DT Review ID ANTERIOR CINGULATE CORTEX; HUMAN ORBITOFRONTAL CORTEX; VENTROMEDIAL PREFRONTAL CORTEX; POSTTRAUMATIC-STRESS-DISORDER; COGNITIVE-BEHAVIORAL THERAPY; CEREBRAL GLUCOSE-METABOLISM; SOCIAL ANXIETY DISORDER; GOAL-DIRECTED BEHAVIOR; MEDIAL FRONTAL-CORTEX; EVENT-RELATED FMRI AB Obsessive-compulsive disorder (OCD) affects approximately 2-3% of the population and is characterized by recurrent intrusive thoughts (obsessions) and repetitive behaviors or mental acts (compulsions), typically performed in response to obsessions or related anxiety. In the past few decades, the prevailing models of OCD pathophysiology have focused on cortico-striatal circuitry. More recent neuroimaging evidence, however, points to critical involvement of the lateral and medial orbitofrontal cortices, the dorsal anterior cingulate cortex and amygdalo-cortical circuitry, in addition to cortico-striatal circuitry, in the pathophysiology of the disorder. In this review, we elaborate proposed features of OCD pathophysiology beyond the classic parallel cortico-striatal pathways and argue that this evidence suggests that fear extinction, in addition to behavioral inhibition, is impaired in OCD. C1 [Milad, Mohammed R.; Rauch, Scott L.] Massachusetts Gen Hosp, Dept Psychiat, Charlestown, MA 02129 USA. [Milad, Mohammed R.; Rauch, Scott L.] Harvard Univ, Sch Med, Charlestown, MA 02129 USA. [Rauch, Scott L.] McLean Hosp, Belmont, MA 02478 USA. RP Milad, MR (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Charlestown, MA 02129 USA. EM milad@nmr.mgh.harvard.edu FU Cyberonics; Medtronic; MircoTransponder Inc.; NIH [R01-MH081975]; DoD [W81XWH-11-2-0079]; Judah Foundation FX S.L.R. has participated in research funded by Cyberonics and Medtronic. M.R.M. has received consulting fees from MircoTransponder Inc.; M.R.M. is supported by NIH grants R01-MH081975, DoD grant W81XWH-11-2-0079 and the Judah Foundation. We would like to thank Katelyn Trecartin and Daria Boratyn for their efforts in generating the figures and their assistance in conducting the meta-analysis. NR 100 TC 166 Z9 173 U1 13 U2 63 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 JAN PY 2012 VL 16 IS 1 SI SI BP 43 EP 51 DI 10.1016/j.tics.2011.11.003 PG 9 WC Behavioral Sciences; Neurosciences; Psychology, Experimental SC Behavioral Sciences; Neurosciences & Neurology; Psychology GA 883BP UT WOS:000299607900012 PM 22138231 ER PT J AU Khanna, D Maranian, P Rothrock, N Cella, D Gershon, R Khanna, PP Spiegel, B Furst, DE Clements, PJ Bechtel, A Hays, RD AF Khanna, Dinesh Maranian, Paul Rothrock, Nan Cella, David Gershon, Richard Khanna, Puja P. Spiegel, Brennan Furst, Daniel E. Clements, Phil J. Bechtel, Amber Hays, Ron D. TI Feasibility and Construct Validity of PROMIS and "Legacy" Instruments in an Academic Scleroderma Clinic SO VALUE IN HEALTH LA English DT Article DE construct validity; health-related quality of life; systemic sclerosis; PROMIS ID INFORMATION-SYSTEM PROMIS; QUALITY-OF-LIFE; QUESTIONNAIRE-DISABILITY INDEX; MEDICAL OUTCOMES; SCLEROSIS; HEALTH; POPULATION; PREVALENCE; DEPRESSION; ARTHRITIS AB Objective: The National Institutes of Health Patient-Reported Outcomes Measurement Information System (PROMIS) roadmap initiative is a cooperative group program of research designed to develop, evaluate, and standardize item banks to measure patient-reported outcomes relevant across medical conditions. The objective of the current study was to assess feasibility and evaluation of the construct validity of PROMIS item banks versus legacy measures in an observational study in systemic sclerosis (SSc). We hypothesized that the PROMIS item banks can be administered in a clinical setting if there is adequate staff support without disrupting the flow of clinic. Methods: Patients with SSc in a single academic center completed computerized adaptive test (CAT) administered PROMIS item banks during the clinic visit and legacy measures (using paper and pencil). The construct validity of PROMIS items was evaluated by examining correlations with corresponding legacy measures using multitrait-multimethod analysis. Results: Participants consisted of 143 SSc patients with an average age of 51.5 years; 71% were female and 68% were white. The average number of items completed for each CAT-administered item bank ranged from 5 to 8 (69 CAT items per patient), and the average time to complete each CAT-administered item bank ranged from 48 seconds to 1.9 minutes per patient (average time similar to 11.9 minutes/ per patient for 11 banks). All correlations between PROMIS domains and respective legacy measures were large and in the hypothesized direction (ranged from 0.61 to 0.82). Conclusion: Our study supports the construct validity of the CAT-administered PROMIS item banks and shows that they can be administered successfully in a clinic with support staff. Future studies should assess the feasibility of PROMIS item banks in a busy clinical practice. C1 [Khanna, Dinesh] Univ Michigan, Scleroderma Program, Div Rheumatol, Dept Internal Med, Ann Arbor, MI 48106 USA. [Maranian, Paul; Furst, Daniel E.; Clements, Phil J.; Bechtel, Amber] Univ Calif Los Angeles, David Geffen Sch Med, Div Rheumatol, Los Angeles, CA 90095 USA. [Rothrock, Nan; Cella, David; Gershon, Richard] Northwestern Univ, Feinberg Sch Med, Dept Med Social Sci, Chicago, IL 60611 USA. [Spiegel, Brennan] Univ Calif Los Angeles, David Geffen Sch Med, Div Digest Dis, Los Angeles, CA 90095 USA. [Spiegel, Brennan] Univ Calif Los Angeles, David Geffen Sch Med, VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90095 USA. [Hays, Ron D.] Univ Calif Los Angeles, David Geffen Sch Med, Div Gen Internal Med & Hlth Serv Res, Los Angeles, CA 90095 USA. [Hays, Ron D.] RAND, Los Angeles, CA USA. RP Khanna, D (reprint author), Univ Michigan, Scleroderma Program, Div Rheumatol, Dept Internal Med, 24 Frank Lloyd Wright Dr,Lobby M,Suite 2500,SPC 5, Ann Arbor, MI 48106 USA. EM khannad@med.umich.edu RI Hays, Ronald/D-5629-2013 FU National Institutes of Health (NIH/ NIAMS) [U01 AR057936A]; National Institutes of Health through NIH [AR052177]; NIAMS [K23 AR053858-05]; Scleroderma Foundation; National Institutes of Health [T32 AR 053463]; UCLA Resource Center for Minority Aging Research/Center for Health Improvement in Minority Elderly (RCMAR/CHIME); NIH/NIA [P30AG021684]; UCLA/ Drew, EXPORT, NCMHD [2P20MD000182] FX D. Khanna, Maranian, Rothrock, Cella, Gershon, Furst, PP Khanna, Spiegel, Bechtel and Hays were supported by a National Institutes of Health Award (NIH/ NIAMS U01 AR057936A), and the National Institutes of Health through the NIH Roadmap for Medical Research Grant (AR052177). D. Khanna is also supported by NIAMS K23 AR053858-05 and the Scleroderma Foundation (New Investigator Award). Dr. PP Khanna was also supported by National Institutes of Health Award (T32 AR 053463). Hays was also supported by the UCLA Resource Center for Minority Aging Research/Center for Health Improvement in Minority Elderly (RCMAR/CHIME), NIH/NIA Grant Award Number P30AG021684, and the UCLA/ Drew Project EXPORT, NCMHD, 2P20MD000182. NR 37 TC 20 Z9 20 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1098-3015 J9 VALUE HEALTH JI Value Health PD JAN-FEB PY 2012 VL 15 IS 1 BP 128 EP 134 DI 10.1016/j.jval.2011.08.006 PG 7 WC Economics; Health Care Sciences & Services; Health Policy & Services SC Business & Economics; Health Care Sciences & Services GA 879GU UT WOS:000299318500015 PM 22264980 ER PT J AU Xu, S Shetterly, S Powers, D Raebel, MA Tsai, TT Ho, PM Magid, D AF Xu, Stanley Shetterly, Susan Powers, David Raebel, Marsha A. Tsai, Thomas T. Ho, P. Michael Magid, David TI Extension of Kaplan-Meier Methods in Observational Studies with Time-Varying Treatment SO VALUE IN HEALTH LA English DT Article DE Kaplan Meier estimates; Observational study; Stabilized weights; Stents; Time-varying treatment ID MARGINAL STRUCTURAL MODELS; PROPENSITY SCORE; INVERSE PROBABILITY; ANTIRETROVIRAL THERAPY; SURVIVAL; EPIDEMIOLOGY; ZIDOVUDINE; MORTALITY; WEIGHTS; SAMPLES AB Objectives: Inverse probability of treatment weighted Kaplan-Meier estimates have been developed to compare two treatments in the presence of confounders in observational studies. Recently, stabilized weights were developed to reduce the influence of extreme inverse probability of treatment-weighted weights in estimating treatment effects. The objective of this research was to use adjusted Kaplan-Meier estimates and modified log-rank and Wilcoxon tests to examine the effect of a treatment that varies over time in an observational study. Methods: We proposed stabilized weight adjusted Kaplan-Meier estimates and modified log-rank and Wilcoxon tests when the treatment was time-varying over the follow-up period. We applied these new methods in examining the effect of an anti-platelet agent, clopidogrel, on subsequent events, including bleeding, myocardial infarction, and death after a drug-eluting stent was implanted into a coronary artery. In this population, clopidogrel use may change over time based on a patient's behavior (e. g., nonadherence) and physicians' recommendations (e. g., end of duration of therapy). Consequently, clopidogrel use was treated as a time-varying variable. Results: We demonstrate that 1) the sample sizes at three chosen time points are almost identical in the original and weighted datasets; and 2) the covariates between patients on and off clopidogrel were well balanced after stabilized weights were applied to the original samples. Conclusions: The stabilized weight-adjusted Kaplan-Meier estimates and modified log-rank and Wilcoxon tests are useful in presenting and comparing survival functions for time-varying treatments in observational studies while adjusting for known confounders. C1 [Xu, Stanley; Shetterly, Susan; Powers, David; Raebel, Marsha A.; Tsai, Thomas T.; Ho, P. Michael; Magid, David] Kaiser Permanente Colorado, Inst Hlth Res, Denver, CO 80111 USA. [Xu, Stanley; Raebel, Marsha A.; Tsai, Thomas T.; Ho, P. Michael; Magid, David] Univ Colorado, Denver, CO 80202 USA. [Tsai, Thomas T.; Ho, P. Michael] Denver VA Med Ctr, Denver, CO USA. RP Xu, S (reprint author), Kaiser Permanente Colorado, Inst Hlth Res, 10065 E Harvard Ave, Denver, CO 80111 USA. EM stan.xu@kp.org FU Strategic Initiatives Funds of Kaiser Permanente Colorado; NIH/NCRR Colorado CTSI [TL1 RR025780]; Agency for Healthcare Research and Quality [290-05-0033]; US Department of Health and Human Services FX This project was supported by Strategic Initiatives Funds of Kaiser Permanente Colorado, supported by NIH/NCRR Colorado CTSI grant No. TL1 RR025780, and funded under Contract No. 290-05-0033 from the Agency for Healthcare Research and Quality, US Department of Health and Human Services as part of the Developing Evidence to Inform Decisions about Effectiveness 16 program. NR 28 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 1098-3015 J9 VALUE HEALTH JI Value Health PD JAN-FEB PY 2012 VL 15 IS 1 BP 167 EP 174 DI 10.1016/j.jval.2011.07.010 PG 8 WC Economics; Health Care Sciences & Services; Health Policy & Services SC Business & Economics; Health Care Sciences & Services GA 879GU UT WOS:000299318500020 PM 22264985 ER PT J AU Rutter, LA Weatherill, RP Taft, CT Orazem, RJ AF Rutter, Lauren A. Weatherill, Robin P. Taft, Casey T. Orazem, Robert J. TI Examining Gender Differences in the Relationship Between Dating Violence Victimization and Anger in College Students SO VIOLENCE AND VICTIMS LA English DT Article DE couples; mental health; anger; gender differences; university; dating violence ID INTIMATE PARTNER VIOLENCE; MENTAL-HEALTH; RELATIONSHIP SATISFACTION; INTERNALIZING SUBTYPES; ABUSE; WOMEN; EXPOSURE; SCALES; RISK; PTSD AB It has been well established that dating violence victimization is associated with various mental health problems. Relatively, little is known about similarities and differences between mental health correlates of dating violence victimization for males and females. We examined the associations between physical and psychological victimization experiences and measures of anger in a sample of 200 male and female undergraduates. Results suggest that men's victimization was more strongly associated with different forms of anger than women's victimization. C1 [Rutter, Lauren A.] Boston Univ, Ctr Anxiety & Related Disorders, Boston, MA 02215 USA. [Weatherill, Robin P.; Taft, Casey T.] VA Boston Healthcare Syst, Natl Ctr PTSD, Boston, MA USA. [Orazem, Robert J.] Ctr Chron Dis Outcomes Res, Minneapolis, MN USA. RP Taft, CT (reprint author), VA Boston Healthcare Syst 116B 4, Natl Ctr PTSD, 150 S Huntington Ave, Boston, MA 02130 USA. EM casey.taft@va.gov NR 25 TC 5 Z9 6 U1 5 U2 17 PU SPRINGER PUBLISHING CO PI NEW YORK PA 11 WEST 42ND STREET, NEW YORK, NY 10036 USA SN 0886-6708 J9 VIOLENCE VICTIMS JI Violence Vict. PY 2012 VL 27 IS 1 BP 70 EP 77 DI 10.1891/0886-6708.27.1.70 PG 8 WC Criminology & Penology SC Criminology & Penology GA 881HC UT WOS:000299472200005 PM 22455185 ER PT J AU Fontes, JD Lyass, A Massaro, JM Rienstra, M Dallmeier, D Schnabel, RB Wang, TJ Vasan, RS Lubitz, SA Magnani, JW Levy, D Ellinor, PT Fox, CS Benjamin, EJ AF Fontes, Joao D. Lyass, Asya Massaro, Joseph M. Rienstra, Michiel Dallmeier, Dhayana Schnabel, Renate B. Wang, Thomas J. Vasan, Ramachandran S. Lubitz, Steven A. Magnani, Jared W. Levy, Daniel Ellinor, Patrick T. Fox, Caroline S. Benjamin, Emelia J. TI Insulin Resistance and Atrial Fibrillation (from the Framingham Heart Study) SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID METABOLIC SYNDROME; DIABETES-MELLITUS; RISK; ATHEROSCLEROSIS; ASSOCIATION; DISEASE; COHORT; MEN AB Diabetes mellitus and obesity are increasing in prevalence and are associated with an elevated risk of atrial fibrillation (AF). Given the aging of the United States population, AF is projected to concomitantly increase in prevalence in the upcoming decades. Both diabetes and obesity are associated with insulin resistance. Whether insulin resistance is an intermediate step for the development of AF is uncertain. We hypothesized that insulin resistance is associated with an increased risk of incident AF. We examined the association of insulin resistance with incident AF using multivariate Cox proportional hazards regression analysis adjusting for the established AF risk factors (i.e., age, gender, systolic blood pressure, hypertension treatment, PR interval, significant heart murmur, heart failure, and body mass index). Of the 3,023 eligible participants (55% women; mean age 59 years) representing 4,583 person-examinations (Framingham Offspring fifth and seventh examination cycles), 279 participants developed AF (9.3%) within <= 10 years of follow-up. With multivariate modeling, insulin resistance was not significantly associated with incident AF (hazard ratio comparing top quartile to other 3 quartiles of homeostatic model assessment index 1.18, 95% confidence interval 0.84 to 1.65, p = 0.34). In a community-based cohort with <= 10 years of follow-up, no significant association was observed between insulin resistance and incident AF. (C) 2012 Elsevier Inc. All rights reserved. (Am J Cardiol 2012;109:87-90) C1 [Fontes, Joao D.; Lyass, Asya; Massaro, Joseph M.; Rienstra, Michiel; Dallmeier, Dhayana; Schnabel, Renate B.; Wang, Thomas J.; Vasan, Ramachandran S.; Magnani, Jared W.; Levy, Daniel; Fox, Caroline S.; Benjamin, Emelia J.] NHLBI, Framingham, MA USA. [Fontes, Joao D.; Lyass, Asya; Massaro, Joseph M.; Rienstra, Michiel; Dallmeier, Dhayana; Schnabel, Renate B.; Wang, Thomas J.; Vasan, Ramachandran S.; Magnani, Jared W.; Levy, Daniel; Fox, Caroline S.; Benjamin, Emelia J.] Boston Univ, Framingham Heart Study, Framingham, MA USA. [Fontes, Joao D.; Vasan, Ramachandran S.; Magnani, Jared W.; Benjamin, Emelia J.] Boston Univ, Sch Med, Dept Med, Sect Cardiovasc Med, Boston, MA 02118 USA. [Lyass, Asya; Massaro, Joseph M.] Boston Univ, Dept Math & Stat, Boston, MA 02215 USA. [Rienstra, Michiel; Wang, Thomas J.; Lubitz, Steven A.; Ellinor, Patrick T.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA USA. [Rienstra, Michiel] Univ Groningen, Dept Cardiol, Univ Med Ctr Groningen, Groningen, Netherlands. [Dallmeier, Dhayana] Boston Univ, Sch Med, Dept Med, Gen Internal Med Sect, Boston, MA 02118 USA. [Schnabel, Renate B.] Johannes Gutenberg Univ Mainz, Dept Med 2, Mainz, Germany. [Lubitz, Steven A.; Ellinor, Patrick T.] Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Boston, MA 02114 USA. [Vasan, Ramachandran S.; Benjamin, Emelia J.] Boston Univ, Sch Med, Dept Med, Prevent Med Sect, Boston, MA 02118 USA. [Levy, Daniel] NHLBI, Ctr Populat Studies, Bethesda, MD 20892 USA. [Fox, Caroline S.] Brigham & Womens Hosp, Div Endocrinol & Metab, Boston, MA 02115 USA. [Fox, Caroline S.] Harvard Univ, Sch Med, Boston, MA USA. [Benjamin, Emelia J.] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. RP Benjamin, EJ (reprint author), NHLBI, Framingham, MA USA. EM emelia@bu.edu RI Schnabel, Renate/F-6527-2014; OI Massaro, Joseph/0000-0002-2682-4812; Ramachandran, Vasan/0000-0001-7357-5970; Benjamin, Emelia/0000-0003-4076-2336; Rienstra, Michiel/0000-0002-2581-070X FU National Institutes of Health/National Heart, Lung, Blood Institute (Bethesda, Maryland) [N01-HC-25195, 6R01-NS17950]; Boston University's Framingham Heart Study (Framingham, Massachusetts [RO1AG028321, 1RC1HL101056, 1R01HL102214, 1R01HL092577, R01HL104156, R21DA027021, K24HL105780]; National Institutes of Health (Bethesda, Maryland) [1RO1HL71039]; Deutsche Forschungsgemeinschaft (German Research Foundation) (Bonn, Germany) [SCHN 1149/1-1]; American Heart Association [09FTF2190028]; Netherlands Organization for Scientific Research (Den Haag, The Netherlands) [825.09.020]; Evans Center for Interdisciplinary Biomedical Research ARC on Atrial Fibrillation Initiative at Boston University (Boston, Massachusetts) FX This study was supported by grants N01-HC-25195 and 6R01-NS17950 from the National Institutes of Health/National Heart, Lung, Blood Institute (Bethesda, Maryland) and Boston University's Framingham Heart Study (Framingham, Massachusetts); grants RO1AG028321, 1RC1HL101056; and 1R01HL102214 (to E. J. Benjamin), 1R01HL092577 (to E. J. Benjamin and P.T. Ellinor), R01HL104156, R21DA027021, and K24HL105780 (to P. T. Ellinor), and 1RO1HL71039 (R. S. Vasan) from the National Institutes of Health (Bethesda, Maryland); Deutsche Forschungsgemeinschaft (German Research Foundation) (Bonn, Germany) Research Fellowship SCHN 1149/1-1 (to R. B. Schnabel); American Heart Association grant 09FTF2190028 (to J.W. Magnani); and Rubicon grant 825.09.020 (to M. Rienstra) from The Netherlands Organization for Scientific Research (Den Haag, The Netherlands). This work was also partially supported by the Evans Center for Interdisciplinary Biomedical Research ARC on Atrial Fibrillation Initiative at Boston University (Boston, Massachusetts) (available from: http://www.bumc.bu.edu/evanscenteribr/thearcs/the-arcs/atrial-fibrillati on-initiative-af-arc/). NR 19 TC 14 Z9 14 U1 0 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 J9 AM J CARDIOL JI Am. J. Cardiol. PD JAN 1 PY 2012 VL 109 IS 1 BP 87 EP 90 DI 10.1016/j.amjcard.2011.08.008 PG 4 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 873RJ UT WOS:000298900400015 PM 21996140 ER PT J AU Suzuki, T Isselbacher, EM Nienaber, CA Pyeritz, RE Eagle, KA Tsai, TT Cooper, JV Januzzi, JL Braverman, AC Montgomery, DG Fattori, R Pape, L Harris, KM Booher, A Oh, JK Peterson, M Ramanath, VS Froehlich, JB AF Suzuki, Toni Isselbacher, Eric M. Nienaber, Christoph A. Pyeritz, Reed E. Eagle, Kim A. Tsai, Thomas T. Cooper, Jeanna V. Januzzi, James L., Jr. Braverman, Alan C. Montgomery, Daniel G. Fattori, Rossella Pape, Linda Harris, Kevin M. Booher, Anna Oh, Jae K. Peterson, Mark Ramanath, Vijay S. Froehlich, James B. TI Type-Selective Benefits of Medications in Treatment of Acute Aortic Dissection (from the International Registry of Acute Aortic Dissection [IRAD]) SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID MARFANS-SYNDROME; MANAGEMENT; DIAGNOSIS; MORTALITY; MORBIDITY; FRONTIERS; VALSARTAN; BLOCKADE; INSIGHTS; DISEASE AB The effects of medications on the outcome of aortic dissection remain poorly understood. We sought to address this by analyzing the International Registry of Acute Aortic Dissection (IRAD) global registry database. A total of 1,301 patients with acute aortic dissection (722 with type A and 579 with type B) with information on their medications at discharge and followed for <= 5 years were analyzed for the effects of the medications on mortality. The initial univariate analysis showed that use of beta blockers was associated with improved survival in all patients (p = 0.03), in patients with type A overall (p = 0.02), and in patients with type A who received surgery (p = 0.006). The analysis also showed that use of calcium channel blockers was associated with improved survival in patients with type B overall (p = 0.02) and in patients with type B receiving medical management (p = 0.03). Multivariate models also showed that the use of beta blockers was associated with improved survival in those with type A undergoing surgery (odds ratio 0.47, 95% confidence interval 0.25 to 0.90, p = 0.02) and the use of calcium channel blockers was associated with improved survival in patients with type B medically treated patients (odds ratio 0.55, 95% confidence interval 0.35 to 0.88, p = 0.01). In conclusion, the present study showed that use of blockers was associated with improved outcome in all patients and in type A patients (overall as well as in those managed surgically). In contrast, use of calcium channel blockers was associated with improved survival selectively in those with type B (overall and in those treated medically). The use of angiotensin-converting enzyme inhibitors did not show association with mortality. (C) 2012 Elsevier Inc. All rights reserved. (Am J Cardiol 2012;109:122-127) C1 [Suzuki, Toni] Univ Tokyo, Tokyo, Japan. [Isselbacher, Eric M.; Januzzi, James L., Jr.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Nienaber, Christoph A.] Univ Hosp, Rostock, Germany. [Pyeritz, Reed E.] Univ Penn, Philadelphia, PA 19104 USA. [Eagle, Kim A.; Cooper, Jeanna V.; Montgomery, Daniel G.; Booher, Anna; Froehlich, James B.] Univ Michigan, Ann Arbor, MI 48109 USA. [Tsai, Thomas T.] Univ Colorado, Denver, CO 80202 USA. [Braverman, Alan C.] Washington Univ, Sch Med, St Louis, MO USA. [Fattori, Rossella] Univ Hosp S Orsola, Bologna, Italy. [Pape, Linda] Univ Massachusetts Hosp, Worcester, MA USA. [Harris, Kevin M.] Minneapolis Heart Inst, Minneapolis, MN USA. [Oh, Jae K.] Mayo Clin, Rochester, MN USA. [Peterson, Mark] St Michaels Hosp, Toronto, AB, Canada. [Ramanath, Vijay S.] Dartmouth Hitchcock Med Ctr, Lebanon, NH 03766 USA. RP Suzuki, T (reprint author), Univ Tokyo, Tokyo, Japan. EM torusuzu-tky@umin.ac.jp NR 25 TC 44 Z9 46 U1 0 U2 3 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI BRIDGEWATER PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD JAN 1 PY 2012 VL 109 IS 1 BP 122 EP 127 DI 10.1016/j.amjcard.2011.08.012 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 873RJ UT WOS:000298900400022 PM 21944678 ER PT J AU Haisley, E Volpp, KG Pellathy, T Loewenstein, G AF Haisley, Emily Volpp, Kevin G. Pellathy, Thomas Loewenstein, George TI The Impact of Alternative Incentive Schemes on Completion of Health Risk Assessments SO AMERICAN JOURNAL OF HEALTH PROMOTION LA English DT Article DE Behavioral Economics; Corporate Wellness Programs; Health Incentives; Health Risk Assessments; Preventive Health Care; Prevention Research ID RANDOMIZED-TRIAL; PROMOTION; LIFE AB Purpose. The biggest challenge for corporate wellness initiatives is low rates of employee participation. We test whether a behavioral economic approach to incentive design (i.e., a lottery) is more effective than a direct economic payment of equivalent monetary value (i.e., a grocery gift certificate) in encouraging employees to complete health risk assessments (HRAs). Design. Employees were assigned to one of three arms. Assignment to a treatment arm versus the nontreatment arm was determined by management. Assignment to an arm among those eligible for treatment was randomized by office. Setting. A large health care management and information technology consulting company. Patients. A total of 1299 employees across 14 offices participated. Intervention. All employees were eligible to receive $25 for completing the HRA. Those in the lottery condition were assigned to teams of four to eight people and, conditional on HRA completion, were entered into a lottery with a prize of $100 (expected value, $25) and a bonus value of an additional $25 if 80% of team members participated. Those in the grocery gift certificate condition who completed an HRA received a $25 grocery gift certificate. Those in the comparison condition received no additional incentive. Measures. HRA completion rates. Analysis. Logistic regression analysis. Results. HRA completion rates were significantly higher among participations in the lottery incentive condition (64%) than in both the grocery gift certificate condition (44%) and the comparison condition (40%). Effects were larger for lower-income employees, as indicated by a significant interaction between income and the lottery incentive. Conclusion. Lottery incentives that incorporate regret aversion and social pressure can provide higher impact for the same amount of money as simple economic incentives. (Am J Health Promot 2012;26131:184-188.) C1 [Loewenstein, George] Carnegie Mellon Univ, Dept Social & Decis Sci, Pittsburgh, PA 15213 USA. [Haisley, Emily] Barclays Wealth, Behav Finance Grp, London, England. [Volpp, Kevin G.] Univ Penn, Ctr Hlth Equ Res & Promot, Philadelphia Vet Affairs Med Ctr,Wharton Sch, Dept Med,Sch Med,Dept Hlth Care Management, Philadelphia, PA 19104 USA. [Pellathy, Thomas] McKinsey & Co Inc, Pittsburgh, PA USA. RP Loewenstein, G (reprint author), Carnegie Mellon Univ, Dept Social & Decis Sci, 5000 Forbes Ave, Pittsburgh, PA 15213 USA. EM g120@andrew.cmu.edu NR 12 TC 24 Z9 24 U1 0 U2 18 PU AMER JOURNAL HEALTH PROMOTION INC PI TROY PA PO BOX 1254, TROY, MI 48099-1254 USA SN 0890-1171 J9 AM J HEALTH PROMOT JI Am. J. Health Promot. PD JAN-FEB PY 2012 VL 26 IS 3 BP 184 EP 188 DI 10.4278/ajhp.100729-ARB-257 PG 5 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 880ZE UT WOS:000299448300010 PM 22208418 ER PT J AU Nestadt, G Wang, Y Grados, MA Riddle, MA Greenberg, BD Knowles, JA Fyer, AJ McCracken, JT Rauch, SL Murphy, DL Rasmussen, SA Cullen, B Piacentini, J Geller, D Pauls, D Bienvenu, OJ Chen, Y Liang, KY Goes, FS Maher, B Pulver, AE Shugart, YY Valle, D Samuels, JF Chang, YC AF Nestadt, G. Wang, Y. Grados, M. A. Riddle, M. A. Greenberg, B. D. Knowles, J. A. Fyer, A. J. McCracken, J. T. Rauch, S. L. Murphy, D. L. Rasmussen, S. A. Cullen, B. Piacentini, J. Geller, D. Pauls, D. Bienvenu, O. J. Chen, Y. Liang, K. Y. Goes, F. S. Maher, B. Pulver, A. E. Shugart, Y. Y. Valle, D. Samuels, J. F. Chang, Y. C. TI Homeobox genes in obsessive-compulsive disorder SO AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS LA English DT Article DE OCD; PBX1; MEIS2; LMX1A; NANOG; genetic association ID OCD COLLABORATIVE GENETICS; EMBRYONIC STEM-CELLS; TRANSCRIPTION FACTORS; POLARIZING REGION; SELF-RENEWAL; MUTANT MICE; DNA-BINDING; PBX MARKS; FAMILY; EXPRESSION AB Background: Despite evidence that obsessive-compulsive disorder (OCD) is a familial neuropsychiatric condition, progress aimed at identifying genetic determinants of the disorder has been slow. The OCD Collaborative Genetics Study (OCGS) has identified several OCD susceptibility loci through linkage analysis. Methods: In this study we investigate two regions on chromosomes 15q and 1q by first refining the linkage region using additional short tandem repeat polymorphic (STRP) markers. We then performed association analysis on single nucleotide polymorphisms (SNP) genotyped (markers placed every 2-4 kb) in the linkage regions in the OCGS sample of 376 rigorously phenotyped affected families. Results: Three SNPs are most strongly associated with OCD: rs11854486 (P=0.00005 [0.046 after adjustment for multiple tests]; genetic relative risk (GRR)=11.1 homozygous and 1.6 heterozygous) and rs4625687 [P=0.00007 (after adjustment=0.06); GRR=2.4] on 15q; and rs4387163 (P=0.0002 (after adjustment=0.08); GRR=1.97) on 1q. The first SNP is adjacent to NANOGP8, the second SNP is in MEIS2, and the third is 150 kb between PBX1 and LMX1A. Conclusions: All the genes implicated by association signals are homeobox genes and are intimately involved in neurodevelopment. PBX1 and MEIS2 exert their effects by the formation of a heterodimeric complex, which is involved in development of the striatum, a brain region involved in the pathophysiology of OCD. NANOGP8 is a retrogene of NANOG, a homeobox transcription factor known to be involved in regulation of neuronal development. These findings need replication; but support the hypothesis that genes involved in striatal development are implicated in the pathogenesis of OCD. (C) 2011 Wiley Periodicals, Inc. C1 [Nestadt, G.; Wang, Y.; Grados, M. A.; Riddle, M. A.; Cullen, B.; Bienvenu, O. J.; Goes, F. S.; Pulver, A. E.; Samuels, J. F.] Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD 21287 USA. [Greenberg, B. D.] Butler Hosp, Brown Med Sch, Dept Psychiat & Human Behav, Providence, RI 02906 USA. [Knowles, J. A.; Rasmussen, S. A.] Univ So Calif, Keck Sch Med, Dept Psychiat, Los Angeles, CA 90033 USA. [Fyer, A. J.] Columbia Univ, Coll Phys & Surg, Dept Psychiat, Manhattan, KS USA. [McCracken, J. T.; Piacentini, J.] Univ Calif Los Angeles, Sch Med, Dept Psychiat & Behav Sci, Los Angeles, CA 90024 USA. [Rauch, S. L.; Geller, D.; Pauls, D.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Rauch, S. L.; Geller, D.; Pauls, D.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Rauch, S. L.; Geller, D.; Pauls, D.] Massachusetts Gen Hosp, Neurodev Genet Unit, Boston, MA 02114 USA. [Murphy, D. L.] NIMH, Clin Sci Lab, NIH, Bethesda, MD 20892 USA. [Chen, Y.; Liang, K. Y.] Johns Hopkins Univ, Dept Biostat, Bloomberg Sch Publ Hlth, Baltimore, MD 21205 USA. [Maher, B.] Johns Hopkins Univ, Dept Mental Hlth, Bloomberg Sch Publ Hlth, Baltimore, MD USA. [Shugart, Y. Y.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. [Shugart, Y. Y.] NIMH, Genom Res Branch, Div Neurosci & Basic Behav Sci, NIH, Bethesda, MD 20892 USA. [Valle, D.] Johns Hopkins Univ, Sch Med, Dept Pediat, Baltimore, MD 21205 USA. [Chang, Y. C.] Univ Maryland, Sch Med, Dept Med, Baltimore, MD 21201 USA. RP Nestadt, G (reprint author), Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, 600 N Wolfe St,Meyer 109, Baltimore, MD 21287 USA. EM gnestadt@jhmi.edu RI Maher, Brion/F-9185-2010; OI Samuels, Jack/0000-0002-6715-7905 FU National Institute of Health [R01-MH-50214, NIH/NCRR/OPD-GCRC RR00052] FX Grant sponsor: National Institute of Health; Grant numbers: R01-MH-50214, NIH/NCRR/OPD-GCRC RR00052. NR 62 TC 10 Z9 10 U1 0 U2 5 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1552-4841 J9 AM J MED GENET B JI Am. J. Med. Genet. B PD JAN PY 2012 VL 159B IS 1 BP 53 EP 60 DI 10.1002/ajmg.b.32001 PG 8 WC Genetics & Heredity; Psychiatry SC Genetics & Heredity; Psychiatry GA 868QC UT WOS:000298536800008 PM 22095678 ER PT J AU Fishman, JA AF Fishman, J. A. TI Prophylaxis, Preemption and Drug Resistance in CMV Infection: Too Little, Too Much or Just Right? SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Editorial Material ID CYTOMEGALOVIRUS C1 Massachusetts Gen Hosp, Transplant Infect Dis & Compromised Host Program, Boston, MA 02114 USA. RP Fishman, JA (reprint author), Massachusetts Gen Hosp, Transplant Infect Dis & Compromised Host Program, Boston, MA 02114 USA. EM jfishman@partners.org NR 5 TC 2 Z9 2 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD JAN PY 2012 VL 12 IS 1 BP 13 EP 14 DI 10.1111/j.1600-6143.2011.03764.x PG 2 WC Surgery; Transplantation SC Surgery; Transplantation GA 875XU UT WOS:000299069300005 PM 21951581 ER PT J AU DiMartini, A Cruz, RJ Dew, MA Fitzgerald, MG Chiappetta, L Myaskovsky, L DeVera, ME AF DiMartini, A. Cruz, R. J., Jr. Dew, M. A. Fitzgerald, M. G. Chiappetta, L. Myaskovsky, L. DeVera, M. E. TI Motives and Decision Making of Potential Living Liver Donors: Comparisons Between Gender, Relationships and Ambivalence SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Article DE Donor screening; living liver donors; psychological characteristics of donors ID BONE-MARROW DONORS; DONATION; OUTCOMES; TRANSPLANTATION AB The motives and decision making of potential living liver donors are critical areas for transplant clinicians evaluating these candidates to understand, yet these topics remain relatively unstudied. Thus, we surveyed 77 prospective living liver donors at the point of donation evaluation using structured instruments to gather more information on their approach to and concerns about donation. We collected information on donation decision making, motives for donation and anticipated social and physical concerns about postdonation outcomes. We examined three additional characteristics of donors: gender, the relationship of the donor to the intended recipient and the presence of ambivalence about donation. Women had more concerns about their family/social responsibilities. Those donating to nonimmediate family were more likely to have been asked to donate but less likely to feel they had to donate. However, ambivalent donors were the most distinct having difficulties and concerns across most areas from their motivations for donating, to deciding to be tested and to donate, to concerns about the postdonation outcomes. We discuss the clinical relevance of these findings to donor evaluation and preparation. C1 [DiMartini, A.; Dew, M. A.; Fitzgerald, M. G.; Chiappetta, L.; Myaskovsky, L.] Univ Pittsburgh, Med Ctr, Dept Psychiat, Pittsburgh, PA 15260 USA. [DiMartini, A.; Cruz, R. J., Jr.; DeVera, M. E.] Univ Pittsburgh, Med Ctr, Dept Transplantat Surg, Pittsburgh, PA USA. [DiMartini, A.; Cruz, R. J., Jr.; Fitzgerald, M. G.; DeVera, M. E.] Univ Pittsburgh, Thomas E Starzl Transplantat Inst, Pittsburgh, PA USA. [Dew, M. A.] Univ Pittsburgh, Dept Psychol, Med Ctr, Pittsburgh, PA 15260 USA. [Dew, M. A.] Univ Pittsburgh, Dept Epidemiol, Med Ctr, Pittsburgh, PA 15261 USA. [Myaskovsky, L.] Univ Pittsburgh, Dept Med, Med Ctr, Pittsburgh, PA USA. [Myaskovsky, L.] VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA USA. RP DiMartini, A (reprint author), Univ Pittsburgh, Med Ctr, Dept Psychiat, Pittsburgh, PA 15260 USA. EM dimartiniaf@upmc.edu FU Starzl Transplant Institute; International Transplant Nurses Society FX This research is funded by grants from the Starzl Transplant Institute Junior Investigator Award (Cruz) and an International Transplant Nurses Society research program grant. NR 22 TC 12 Z9 12 U1 0 U2 3 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD JAN PY 2012 VL 12 IS 1 BP 136 EP 151 DI 10.1111/j.1600-6143.2011.03805.x PG 16 WC Surgery; Transplantation SC Surgery; Transplantation GA 875XU UT WOS:000299069300018 PM 22081865 ER EF