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John Blair Deaver, M.D., And His Marvelous Retractor., Timothy E. Newhook, Md, Charles J. Yeo, Md, Pinckney J. Maxwell, Iv, Md Feb 2012

John Blair Deaver, M.D., And His Marvelous Retractor., Timothy E. Newhook, Md, Charles J. Yeo, Md, Pinckney J. Maxwell, Iv, Md

Department of Surgery Gibbon Society Historical Profiles

John Blair Deaver was born near Buck, Pennsylvania, in Lancaster County on July 25, 1855, to Dr. Joshua Montgomery Deaver and Elizabeth Clair Moore. The elder Deaver was a reputable country physician, educated at the University of Maryland, who fathered three physicians and a college president. John Blair Deaver (Fig. 1) went to boarding school at West Nottingham Academy in Maryland. After boarding school he taught in Lancaster County country schools to raise funds to attend the nation’s first medical school, the University of Pennsylvania. On receiving his M.D. degree in 1878, Dr. Deaver completed 1-year internships at both Germantown …


Does International Normalized Ratio Level Predict Pulmonary Embolism?, Patricia Hansen, Benjamin Zmistowski, Camilo Restrepo, Javad Parvizi, Richard H Rothman Feb 2012

Does International Normalized Ratio Level Predict Pulmonary Embolism?, Patricia Hansen, Benjamin Zmistowski, Camilo Restrepo, Javad Parvizi, Richard H Rothman

Rothman Institute Papers

BACKGROUND: Preventing pulmonary embolism is a priority after major musculoskeletal surgery. The literature contains discrepant data regarding the influence of anticoagulation on the incidence of pulmonary embolism after joint arthroplasty. The American College of Chest Physicians guidelines recommend administration of oral anticoagulants (warfarin), aiming for an international normalized ratio (INR) level between 2 and 3. However, recent studies show aggressive anticoagulation (INR > 2) can lead to hematoma formation and increased risk of subsequent infection.

QUESTIONS/PURPOSES: We asked whether an INR greater than 2 protects against pulmonary embolism.

PATIENTS AND METHODS: We identified 9112 patients with 10,122 admissions for joint arthroplasty …


Mir-25 Targets Tnf-Related Apoptosis Inducing Ligand (Trail) Death Receptor-4 And Promotes Apoptosis Resistance In Cholangiocarcinoma., Nataliya Razumilava, Steve F. Bronk, Rory L. Smoot, Christian D. Fingas, Nathan W. Werneburg, Lewis R. Roberts, Justin L. Mott Feb 2012

Mir-25 Targets Tnf-Related Apoptosis Inducing Ligand (Trail) Death Receptor-4 And Promotes Apoptosis Resistance In Cholangiocarcinoma., Nataliya Razumilava, Steve F. Bronk, Rory L. Smoot, Christian D. Fingas, Nathan W. Werneburg, Lewis R. Roberts, Justin L. Mott

Journal Articles: Biochemistry & Molecular Biology

It has been established that microRNA expression and function contribute to phenotypic features of malignant cells, including resistance to apoptosis. Although targets and functional roles for a number of microRNAs have been described in cholangiocarcinoma, many additional microRNAs dysregulated in this tumor have not been assigned functional roles. In this study, we identify elevated miR-25 expression in malignant cholangiocarcinoma cell lines as well as patient samples. In cultured cells, treatment with the Smoothened inhibitor, cyclopamine, reduced miR-25 expression, suggesting Hedgehog signaling stimulates miR-25 production. Functionally, miR-25 was shown to protect cells against TNF-related apoptosis-inducing ligand (TRAIL)-induced apoptosis. Correspondingly, antagonism of …


The Formal And Informal Surgical Ethics Curriculum: Views Of Resident And Staff Surgeons In Toronto., Frazer Howard, Martin F. Mckneally, Ross E.G. Upshur, Alex V. Levin Feb 2012

The Formal And Informal Surgical Ethics Curriculum: Views Of Resident And Staff Surgeons In Toronto., Frazer Howard, Martin F. Mckneally, Ross E.G. Upshur, Alex V. Levin

Wills Eye Hospital Papers

BACKGROUND: Understanding what staff surgeons think surgical trainees should learn and the ethical issues that trainees need to manage can strengthen surgical ethics education.

METHODS: Participants were recruited from the 15 surgical specialty and subspecialty programs at the University of Toronto. Semistructured interviews and focus groups were conducted with 13 ethics coordinators from the surgical staff and 64 resident trainees. Data were analyzed qualitatively using modified thematic analysis.

RESULTS: All coordinators and trainees felt that ethics education was an important component of surgical training. Real cases, varying teaching methods, and teachers with applicable clinical experience were valued. Trainees identified intraprofessional …


Using Health Information Technology To Engage Communities In Health, Education, And Research, Lisa K. Marriott, David A. Nelson, Shauntice Allen, Karen Calhoun, Christina Eldredge, Kim S. Kimminau, Robert J. Lucero, Fernando Pineda-Reyes, Bernice B. Rumala, Arti P. Varanasi, June S. Wasser, Jackilen Shannon Feb 2012

Using Health Information Technology To Engage Communities In Health, Education, And Research, Lisa K. Marriott, David A. Nelson, Shauntice Allen, Karen Calhoun, Christina Eldredge, Kim S. Kimminau, Robert J. Lucero, Fernando Pineda-Reyes, Bernice B. Rumala, Arti P. Varanasi, June S. Wasser, Jackilen Shannon

School of Information Faculty Publications

The August 2011 Clinical and Translational Science Awards conference "Using IT to Improve Community Health: How Health Care Reform Supports Innovation" convened four "Think Tank" sessions. Thirty individuals, representing various perspectives on community engagement, attended the "Health information technology (HIT) as a resource to improve community health and education" session, which focused on using HIT to improve patient health, education, and research involvement. Participants discussed a range of topics using a semistructured format. This article describes themes and lessons that emerged from that session, with a particular focus on using HIT to engage communities to improve health and reduce health …


Decorin-Mediated Inhibition Of Colorectal Cancer Growth And Migration Is Associated With E-Cadherin In Vitro And In Mice., Xiuli Bi, Nicole M Pohl, Zhibin Qian, George R Yang, Yuan Gou, Grace Guzman, Andre Kajdacsy-Balla, Renato V Iozzo, Wancai Yang Feb 2012

Decorin-Mediated Inhibition Of Colorectal Cancer Growth And Migration Is Associated With E-Cadherin In Vitro And In Mice., Xiuli Bi, Nicole M Pohl, Zhibin Qian, George R Yang, Yuan Gou, Grace Guzman, Andre Kajdacsy-Balla, Renato V Iozzo, Wancai Yang

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Previous studies have shown that decorin expression is significantly reduced in colorectal cancer tissues and cancer cells, and genetic deletion of the decorin gene is sufficient to cause intestinal tumor formation in mice, resulting from a downregulation of p21, p27(kip1) and E-cadherin and an upregulation of β-catenin signaling [Bi,X. et al. (2008) Genetic deficiency of decorin causes intestinal tumor formation through disruption of intestinal cell maturation. Carcinogenesis, 29, 1435-1440]. However, the regulation of E-cadherin by decorin and its implication in cancer formation and metastasis is largely unknown. Using a decorin knockout mouse model (Dcn(-/-) mice) and manipulated expression of decorin …


Surgical Outcome In Pet-Positive, Mri-Negative Patients With Temporal Lobe Epilepsy, Carla Lopinto-Khoury, Michael R. Sperling, Christopher Skidmore, Maromi Nei, James Evans, Ashwini Sharan, Scott Mintzer Feb 2012

Surgical Outcome In Pet-Positive, Mri-Negative Patients With Temporal Lobe Epilepsy, Carla Lopinto-Khoury, Michael R. Sperling, Christopher Skidmore, Maromi Nei, James Evans, Ashwini Sharan, Scott Mintzer

Department of Neurology Faculty Papers

PURPOSE:

Fluorodeoxyglucose positron emission computed tomography (FDG-PET) hypometabolism is important for surgical planning in patients with temporal lobe epilepsy (TLE), but its significance remains unclear in patients who do not have evidence of mesial temporal sclerosis (MTS) on magnetic resonance imaging (MRI). We examined surgical outcomes in a group of PET-positive, MRI-negative patients and compared them with those of patients with MTS.

METHODS:

We queried the Thomas Jefferson University Surgical Epilepsy Database for patients who underwent anterior temporal lobectomy (ATL) from 1991 to 2009 and who had unilateral temporal PET hypometabolism without an epileptogenic lesion on MRI (PET+/MRI-). We compared …


Thoratec Heartmate Ii(®) Left Ventricular Assist Device Implantation In Patient With Patent Ventriculoperitoneal Shunt., Kentaro Yamane, Linda J Bogar, Shigeki Tabata, Hitoshi Hirose Jan 2012

Thoratec Heartmate Ii(®) Left Ventricular Assist Device Implantation In Patient With Patent Ventriculoperitoneal Shunt., Kentaro Yamane, Linda J Bogar, Shigeki Tabata, Hitoshi Hirose

Department of Surgery Faculty Papers

We report a case of HeartMate II® left ventricular assist device (LVAD) implantation as a destination therapy in a patient with a patent ventriculoperitoneal (VP) shunt after being suffered from subarachnoid hemorrhage. Because the patient's VP shunt was running through her right anterior chest and abdominal wall, a driveline exit site was selected in her left upper quadrant to avoid unnecessary perioperative complication in relation to the patent VP shunt tube. Tailored driveline placement was a key element of this LVAD implantation in this already sick patient with multiple comorbidities.


Longitudinal Impact Of The Project Paths On Adolescent Risk Behavior: What Happened After Five Years?, Daniel T. L. Shek, Lu Yu Jan 2012

Longitudinal Impact Of The Project Paths On Adolescent Risk Behavior: What Happened After Five Years?, Daniel T. L. Shek, Lu Yu

Pediatrics Faculty Publications

The present study investigated the longitudinal impact of the Project PATHS, a large-scale curriculum-based positive youth development program in Hong Kong, on the development of adolescents' risk behavior over a period of five years. Using a longitudinal randomized controlled design, eight waves of data were collected from 19 experimental schools in which students participated in the Project PATHS (N = 2,850 at Wave 8) and 24 control schools without joining the Project PATHS (N = 3,640 at Wave 8). At each wave, students responded to measures assessing their current risk behaviors, including delinquency, use of different types of drug, and …


Predictors Of Survival In A Cohort Of Patients With Polymyositis And Dermatomyositis: Effect Of Corticosteroids, Methotrexate And Azathioprine, Elena Schiopu, Kristine Phillips, Paul M. Macdonald, Leslie J. Crofford, Emily C. Somers Jan 2012

Predictors Of Survival In A Cohort Of Patients With Polymyositis And Dermatomyositis: Effect Of Corticosteroids, Methotrexate And Azathioprine, Elena Schiopu, Kristine Phillips, Paul M. Macdonald, Leslie J. Crofford, Emily C. Somers

Internal Medicine Faculty Publications

INTRODUCTION: The idiopathic inflammatory myopathies are rare diseases for which data regarding the natural history, response to therapies and factors affecting mortality are needed. We performed this study to examine the effects of treatment and clinical features on survival in polymyositis and dermatomyositis patients.

METHODS: A total of 160 consecutive patients (77 with polymyositis and 83 with dermatomyositis) seen at the University of Michigan from 1997 to 2003 were included. Medical records were abstracted for clinical, laboratory and therapeutic data, including initial steroid regimen and immunosuppressive use. State vital records were utilized to derive mortality and cause of death data. …


Influence Of Medical Journal Press Releases On The Quality Of Associated Newspaper Coverage: Retrospective Cohort Study, Lisa M. Schwartz, Steven Woloshin, Alice Andrews, Therese A. Stukel Jan 2012

Influence Of Medical Journal Press Releases On The Quality Of Associated Newspaper Coverage: Retrospective Cohort Study, Lisa M. Schwartz, Steven Woloshin, Alice Andrews, Therese A. Stukel

Dartmouth Scholarship

Objective: To determine whether the quality of press releases issued by medical journals can influence the quality of associated newspaper stories.


Systematic Review Of Peer Support For Breastfeeding Continuation: Metaregression Analysis Of The Effect Of Setting, Intensity, And Timing, Kate Jolly, Lucy Annang Ingram Phd, Khalid S. Khan, Jonathan J. Deeks, Nick Freemantle, Christine Macarthur Jan 2012

Systematic Review Of Peer Support For Breastfeeding Continuation: Metaregression Analysis Of The Effect Of Setting, Intensity, And Timing, Kate Jolly, Lucy Annang Ingram Phd, Khalid S. Khan, Jonathan J. Deeks, Nick Freemantle, Christine Macarthur

Faculty Publications

OBJECTIVE: To examine the effect of setting, intensity, and timing of peer support on breast feeding. DESIGN: Systematic review and metaregression analysis of randomised controlled trials. DATA SOURCES: Cochrane Library, Medline, CINAHL, the National Research Register, and British Nursing Index were searched from inception or from 1980 to 2011. Review methods Study selection, data abstraction, and quality assessment were carried out independently and in duplicate. Risk ratios and 95% confidence intervals were calculated for individual studies and pooled. Effects were estimated for studies grouped according to setting (high income countries, low or middle income countries, and the United Kingdom), intensity …


Protocol For A Randomized Controlled Trial Of A Specialized Health Coaching Intervention To Prevent Excessive Gestational Weight Gain And Postpartum Weight Retention In Women: The Hipp Study., Helen Skouteris, Marita Mccabe, Jeannette Milgrom, Bridie Kent, Lauren J. Bruce, Cathrine Mihalopoulos, Sharon J. Herring, Malcolm Barnett, Denise Patterson, Glyn Teale, Janette Gale Jan 2012

Protocol For A Randomized Controlled Trial Of A Specialized Health Coaching Intervention To Prevent Excessive Gestational Weight Gain And Postpartum Weight Retention In Women: The Hipp Study., Helen Skouteris, Marita Mccabe, Jeannette Milgrom, Bridie Kent, Lauren J. Bruce, Cathrine Mihalopoulos, Sharon J. Herring, Malcolm Barnett, Denise Patterson, Glyn Teale, Janette Gale

School of Nursing and Midwifery

BACKGROUND: Pregnancy is a time of significant physiological and physical change for women. In particular, it is a time at which many women are at risk of gaining excessive weight. We describe the rationale and methods of the Health in Pregnancy and Post-birth (HIPP) Study, a study which aims primarily to determine the effectiveness of a specialized health coaching (HC) intervention during pregnancy, compared to education alone, in preventing excessive gestational weight gain and postpartum weight retention 12 months post birth. A secondary aim of this study is to evaluate the mechanisms by which our HC intervention impacts on weight …


A Spatial Cluster Analysis Of Tractor Overturns In Kentucky From 1960 To 2002, Daniel M. Saman, Henry P. Cole, Agricola Odoi, Melvin L. Myers, Daniel I. Carey, Susan C. Westneat Jan 2012

A Spatial Cluster Analysis Of Tractor Overturns In Kentucky From 1960 To 2002, Daniel M. Saman, Henry P. Cole, Agricola Odoi, Melvin L. Myers, Daniel I. Carey, Susan C. Westneat

Epidemiology and Environmental Health Faculty Publications

BACKGROUND: Agricultural tractor overturns without rollover protective structures are the leading cause of farm fatalities in the United States. To our knowledge, no studies have incorporated the spatial scan statistic in identifying high-risk areas for tractor overturns. The aim of this study was to determine whether tractor overturns cluster in certain parts of Kentucky and identify factors associated with tractor overturns.

METHODS: A spatial statistical analysis using Kulldorff's spatial scan statistic was performed to identify county clusters at greatest risk for tractor overturns. A regression analysis was then performed to identify factors associated with tractor overturns.

RESULTS: The spatial analysis …


Primary Care Providers’ Perspectives On Online Weight-Loss Programs: A Big Wish List, Kevin O Hwang, Heather L Stuckey, Monica C Chen, Jennifer L Kraschnewski, Samuel N Forjuoh, Jennifer M Poger, Kathleen M Mctigue, Christopher N Sciamanna Jan 2012

Primary Care Providers’ Perspectives On Online Weight-Loss Programs: A Big Wish List, Kevin O Hwang, Heather L Stuckey, Monica C Chen, Jennifer L Kraschnewski, Samuel N Forjuoh, Jennifer M Poger, Kathleen M Mctigue, Christopher N Sciamanna

Faculty, Staff and Student Publications

BACKGROUND: Integrating online weight-loss programs into the primary care setting could yield substantial public health benefit. Little is known about primary care providers' perspectives on online weight-loss programs.

OBJECTIVE: To assess primary care providers' perspectives on online weight-loss programs.

METHODS: We conducted focus group discussions with providers in family medicine, internal medicine, and combined internal medicine/pediatrics in Texas and Pennsylvania, USA. Open-ended questions addressed their experience with and attitudes toward online weight-loss programs; useful characteristics of existing online weight-loss programs; barriers to referring patients to online weight-loss programs; and preferred characteristics of an ideal online weight-loss program. Transcripts were analyzed …


Inflammatory Signaling Compromises Cell Responses To Interferon Alpha., W-C Huangfu, J Qian, C Liu, J Liu, A E Lokshin, D P Baker, H Rui, S Y Fuchs Jan 2012

Inflammatory Signaling Compromises Cell Responses To Interferon Alpha., W-C Huangfu, J Qian, C Liu, J Liu, A E Lokshin, D P Baker, H Rui, S Y Fuchs

Department of Cancer Biology Faculty Papers

Interferon alpha (IFNα) is widely used for treatment of melanoma and certain other malignancies. This cytokine as well as the related IFNβ exerts potent anti-tumorigenic effects; however, their efficacy in patients is often suboptimal. Here, we report that inflammatory signaling impedes the effects of IFNα/β. Melanoma cells can secrete pro-inflammatory cytokines that inhibit cellular responses to IFNα/β via activating the ligand-independent pathway for the phosphorylation and subsequent ubiquitination and accelerated degradation of the IFNAR1 chain of type I IFN receptor. Catalytic activity of the p38 protein kinase was required for IFNAR1 downregulation and inhibition of IFNα/β signaling induced by proinflammatory …


The Social Production Of Substance Abuse And Hiv/Hcv Risk: An Exploratory Study Of Opioid-Using Immigrants From The Former Soviet Union Living In New York City, Honoria Guarino, Sarah K. Moore, Lisa A. Marsch, Sal Florio Jan 2012

The Social Production Of Substance Abuse And Hiv/Hcv Risk: An Exploratory Study Of Opioid-Using Immigrants From The Former Soviet Union Living In New York City, Honoria Guarino, Sarah K. Moore, Lisa A. Marsch, Sal Florio

Dartmouth Scholarship

Several former Soviet countries have witnessed the rapid emergence of major epidemics of injection drug use (IDU) and associated HIV/HCV, suggesting that immigrants from the former Soviet Union (FSU) may be at heightened risk for similar problems. This exploratory study examines substance use patterns among the understudied population of opioid-using FSU immigrants in the U.S., as well as social contextual factors that may increase these immigrants' susceptibility to opioid abuse and HIV/HCV infection. In-depth interviews were conducted with 10 FSU immigrants living in New York City who initiated opioid use in adolescence or young adulthood, and with 6 drug treatment …


Usp8 Promotes Smoothened Signaling By Preventing Its Ubiquitination And Changing Its Subcellular Localization, Ruohan Xia, Hongge Jia, Junkai Fan, Yajuan Liu, Jianhang Jia Jan 2012

Usp8 Promotes Smoothened Signaling By Preventing Its Ubiquitination And Changing Its Subcellular Localization, Ruohan Xia, Hongge Jia, Junkai Fan, Yajuan Liu, Jianhang Jia

Molecular and Cellular Biochemistry Faculty Publications

The seven transmembrane protein Smoothened (Smo) is a critical component of the Hedgehog (Hh) signaling pathway and is regulated by phosphorylation, dimerization, and cell-surface accumulation upon Hh stimulation. However, it is not clear how Hh regulates Smo accumulation on the cell surface or how Hh regulates the intracellular trafficking of Smo. In addition, little is known about whether ubiquitination is involved in Smo regulation. In this study, we demonstrate that Smo is multi-monoubiquitinated and that Smo ubiquitination is inhibited by Hh and by phosphorylation. Using an in vivo RNAi screen, we identified ubiquitin-specific protease 8 (USP8) as a deubiquitinase that …


Conformational Altered P53 As An Early Marker Of Oxidative Stress In Alzheimer's Disease, Laura Buizza, Giovanna Cenini, Cristina Lanni, Giulia Ferrari-Toninelli, Chiara Prandelli, Stefano Govoni, Erica Buoso, Marco Racchi, Maria Barcikowska, Maria Styczynska, Aleksandra Szybinska, D. Allan Butterfield, Maurizio Memo, Daniela Uberti Jan 2012

Conformational Altered P53 As An Early Marker Of Oxidative Stress In Alzheimer's Disease, Laura Buizza, Giovanna Cenini, Cristina Lanni, Giulia Ferrari-Toninelli, Chiara Prandelli, Stefano Govoni, Erica Buoso, Marco Racchi, Maria Barcikowska, Maria Styczynska, Aleksandra Szybinska, D. Allan Butterfield, Maurizio Memo, Daniela Uberti

Sanders-Brown Center on Aging Faculty Publications

In order to study oxidative stress in peripheral cells of Alzheimer's disease (AD) patients, immortalized lymphocytes derived from two peculiar cohorts of patients, referring to early onset AD (EOSAD) and subjects harboured AD related mutation (ADmut), were used. Oxidative stress was evaluated measuring i) the typical oxidative markers, such as HNE Michel adducts, 3 Nitro-Tyrosine residues and protein carbonyl on protein extracts, ii) and the antioxidant capacity, following the enzymatic kinetic of superoxide dismutase (SOD), glutathione peroxidase (GPx) and glutathione reductase (GRD). We found that the signs of oxidative stress, measured as oxidative marker levels, were evident only in ADmut …


Hiv-1 Tat Triggers Nuclear Localization Of Zo-1 Via Rho Signaling And Camp Response Element-Binding Protein Activation, Yu Zhong, Bei Zhang, Sung Yong Eum, Michal Toborek Jan 2012

Hiv-1 Tat Triggers Nuclear Localization Of Zo-1 Via Rho Signaling And Camp Response Element-Binding Protein Activation, Yu Zhong, Bei Zhang, Sung Yong Eum, Michal Toborek

Neurosurgery Faculty Publications

The human immunodeficiency virus (HIV)-specific protein trans-activator of transcription (Tat) can contribute to the dysfunction of brain endothelial cells and HIV trafficking into the brain by disrupting tight junction (TJ) integrity at the blood–brain barrier (BBB) level. Specific TJ proteins, such as zonula occludens (ZO) proteins, localize not only at the cell–cell borders but are also present in the nuclei. The objective of the present study was to evaluate the mechanisms and significance of Tat-induced nuclear localization of ZO-1. Treatment of a brain endothelial cell line (hCMEC/D3 cells) with Tat resulted in a decrease in total levels of ZO-1 but …


The Role Of Ezh2 In The Regulation Of The Activity Of Matrix Metalloproteinases In Prostate Cancer Cells., Yong Jae Shin, Jeong-Ho Kim Jan 2012

The Role Of Ezh2 In The Regulation Of The Activity Of Matrix Metalloproteinases In Prostate Cancer Cells., Yong Jae Shin, Jeong-Ho Kim

Biochemistry and Molecular Medicine Faculty Publications

Degradation of the extracellular matrix (ECM), a critical step in cancer metastasis, is determined by the balance between MMPs (matrix metalloproteinases) and their inhibitors TIMPs (tissue inhibitors of metalloproteinases). In cancer cells, this balance is shifted towards MMPs, promoting ECM degradation. Here, we show that EZH2 plays an active role in this process by repressing the expression of TIMP2 and TIMP3 in prostate cancer cells. The TIMP genes are derepressed by knockdown of EZH2 expression in human prostate cancer cells but repressed by overexpression of EZH2 in benign human prostate epithelial cells. EZH2 catalyzes H3K27 trimethylation and subsequent DNA methylation …


Effect Of Spermidine On Misfolding And Interactions Of Alpha-Synuclein., Alexey V. Krasnoslobodtsev, Jie Peng, Josephat M. Asiago, Jagadish Hindupur, Jean-Christophe Rochet, Yuri L. Lyubchenko Jan 2012

Effect Of Spermidine On Misfolding And Interactions Of Alpha-Synuclein., Alexey V. Krasnoslobodtsev, Jie Peng, Josephat M. Asiago, Jagadish Hindupur, Jean-Christophe Rochet, Yuri L. Lyubchenko

Journal Articles: Pharmaceutical Sciences

Alpha-synuclein (α-Syn) is a 140 aa presynaptic protein which belongs to a group of natively unfolded proteins that are unstructured in aqueous solutions. The aggregation rate of α-Syn is accelerated in the presence of physiological levels of cellular polyamines. Here we applied single molecule AFM force spectroscopy to characterize the effect of spermidine on the very first stages of α-Syn aggregation--misfolding and assembly into dimers. Two α-Syn variants, the wild-type (WT) protein and A30P, were studied. The two protein molecules were covalently immobilized at the C-terminus, one at the AFM tip and the other on the substrate, and intermolecular interactions …


Posttraumatic Stress Disorder Prevalence And Risk Of Recurrence In Acute Coronary Syndrome Patients: A Meta-Analytic Review., D. Edmondson, S. Richardson, L. Falzon, K. W. Davidson, M. A. Mills, Y. Neria Jan 2012

Posttraumatic Stress Disorder Prevalence And Risk Of Recurrence In Acute Coronary Syndrome Patients: A Meta-Analytic Review., D. Edmondson, S. Richardson, L. Falzon, K. W. Davidson, M. A. Mills, Y. Neria

Journal Articles

BACKGROUND: Acute coronary syndromes (ACS; myocardial infarction or unstable angina) can induce posttraumatic stress disorder (PTSD), and ACS-induced PTSD may increase patients' risk for subsequent cardiac events and mortality.

OBJECTIVE: To determine the prevalence of PTSD induced by ACS and to quantify the association between ACS-induced PTSD and adverse clinical outcomes using systematic review and meta-analysis.

DATA SOURCES: Articles were identified by searching Ovid MEDLINE, PsycINFO, and Scopus, and through manual search of reference lists.

METHODOLOGY/PRINCIPAL FINDINGS: Observational cohort studies that assessed PTSD with specific reference to an ACS event at least 1 month prior. We extracted estimates of the …


Cooperative Cluster Formation, Dna Bending And Base-Flipping By O6-Alkylguanine-Dna Alkyltransferase, Ingrid Tessmer, Manana Melikishvili, Michael G. Fried Jan 2012

Cooperative Cluster Formation, Dna Bending And Base-Flipping By O6-Alkylguanine-Dna Alkyltransferase, Ingrid Tessmer, Manana Melikishvili, Michael G. Fried

Center for Structural Biology Faculty Publications

O6-Alkylguanine-DNA alkyltransferase (AGT) repairs mutagenic O6-alkylguanine and O4-alkylthymine adducts in DNA, protecting the genome and also contributing to the resistance of tumors to chemotherapeutic alkylating agents. AGT binds DNA cooperatively, and cooperative interactions are likely to be important in lesion search and repair. We examined morphologies of complexes on long, unmodified DNAs, using analytical ultracentrifugation and atomic force microscopy. AGT formed clusters of ≤11 proteins. Longer clusters, predicted by the McGhee–von Hippel model, were not seen even at high [protein]. Interestingly, torsional stress due to DNA unwinding has the potential to limit cluster size …


Follicle-Stimulating Hormone Is Independently Associated With Lean Mass But Not Bmd In Younger Postmenopausal Women, Margaret L Gourlay, Bonny Specker, Chenxi Li, Catherine A. Hammett-Stabler, Jordan B. Renner, Janet E Rubin Jan 2012

Follicle-Stimulating Hormone Is Independently Associated With Lean Mass But Not Bmd In Younger Postmenopausal Women, Margaret L Gourlay, Bonny Specker, Chenxi Li, Catherine A. Hammett-Stabler, Jordan B. Renner, Janet E Rubin

Ethel Austin Martin Program Publications

PURPOSE: Increased follicle-stimulating hormone (FSH) has been associated with lower bone mineral density (BMD) in animal models and longitudinal studies of women, but a direct effect has not been demonstrated.
METHODS: We tested associations between FSH, non-bone body composition measures and BMD in 94 younger (aged 50 to 64 years) postmenopausal women without current use of hormone therapy, adjusting for sex hormone concentrations and clinical risk factors for osteoporosis. Lean mass, fat mass and areal BMD (aBMD) at the spine, femoral neck and total hip were measured using dual energy X-ray absorptiometry (DXA). Volumetric BMD (vBMD) was measured at the …


Antibiotics For Leptospirosis, David Brett-Major, Rodney Coldren Jan 2012

Antibiotics For Leptospirosis, David Brett-Major, Rodney Coldren

Journal Articles: Epidemiology

BACKGROUND: Leptospirosis has a wide-ranging clinical and public health impact. Leptospira are globally distributed. Case attack rates are as high as 1:4 to 2:5 persons in exposed populations. In some settings mortality has exceeded 10% of infected people. The benefit of antibiotic therapy in the disease has been unclear.

OBJECTIVES: We sought to characterise the risks and benefits associated with use of antibiotic therapy in the management of leptospirosis.

SEARCH METHODS: We searched the The Cochrane Hepato-Biliary Group Controlled Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library, MEDLINE, EMBASE, and Science Citation Index Expanded …


Examining Fatigue In Copd: Development, Validity And Reliability Of A Modified Version Of Facit-F Scale, Khaled Al-Shair, Hana Muellerova, Janelle Yorke, Stephen I. Rennard, Emiel F.M. Wouters, Nicola A. Hanania, Amir Sharafkhaneh, Jørgen Vestbo, Eclipse Investigators Jan 2012

Examining Fatigue In Copd: Development, Validity And Reliability Of A Modified Version Of Facit-F Scale, Khaled Al-Shair, Hana Muellerova, Janelle Yorke, Stephen I. Rennard, Emiel F.M. Wouters, Nicola A. Hanania, Amir Sharafkhaneh, Jørgen Vestbo, Eclipse Investigators

Journal Articles: Pulmonary & Critical Care Med

INTRODUCTION: Fatigue is a disruptive symptom that inhibits normal functional performance of COPD patients in daily activities. The availability of a short, simple, reliable and valid scale would improve assessment of the characteristics and influence of fatigue in COPD.

METHODS: At baseline, 2107 COPD patients from the ECLIPSE cohort completed the Functional Assessment of Chronic Illness Therapy Fatigue (FACIT-F) scale. We used well-structured classic method, the principal components analysis (PCA) and Rasch analysis for structurally examining the 13-item FACIT-F.

RESULTS: Four items were less able to capture fatigue characteristics in COPD and were deleted. PCA was applied to the remaining …


Tropical Medicine Training In The Department Of Defense, Rodney L. Coldren, David Brett-Major, Patrick W. Hickey, Eric Garges, Peter J. Weina, Paula Corrigan, Gerald Quinnan Jan 2012

Tropical Medicine Training In The Department Of Defense, Rodney L. Coldren, David Brett-Major, Patrick W. Hickey, Eric Garges, Peter J. Weina, Paula Corrigan, Gerald Quinnan

Journal Articles: Epidemiology

No abstract provided.


Effects Of Inhaled Corticosteroids On Airway Inflammation In Chronic Obstructive Pulmonary Disease: A Systematic Review And Meta-Analysis, Rachel Jen, Stephen I. Rennard, Don D. Sin Jan 2012

Effects Of Inhaled Corticosteroids On Airway Inflammation In Chronic Obstructive Pulmonary Disease: A Systematic Review And Meta-Analysis, Rachel Jen, Stephen I. Rennard, Don D. Sin

Journal Articles: Pulmonary & Critical Care Med

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is characterized by chronic inflammation in the small airways. The effect of inhaled corticosteroids (ICS) on lung inflammation in COPD remains uncertain. We sought to determine the effects of ICS on inflammatory indices in bronchial biopsies and bronchoalveolar lavage fluid of patients with COPD.

METHODS: We searched Medline, Embase, Cinahl, and the Cochrane database for randomized, controlled clinical trials that used bronchial biopsies and bronchoalveolar lavage to evaluate the effects of ICS in stable COPD. For each chosen study, we calculated the mean differences in the concentrations of inflammatory cells before and after treatment …


A Randomized Placebo-Controlled Trial Of Varenicline For Smoking Cessation Allowing Flexible Quit Dates, Stephen I. Rennard, John Hughes, Paul M. Cinciripini, Eva Kralikova, Tobias Raupach, Carmen Arteaga, Lisa B. St Aubin, Cristina Russ, The Flexible Quit Date Study Group Jan 2012

A Randomized Placebo-Controlled Trial Of Varenicline For Smoking Cessation Allowing Flexible Quit Dates, Stephen I. Rennard, John Hughes, Paul M. Cinciripini, Eva Kralikova, Tobias Raupach, Carmen Arteaga, Lisa B. St Aubin, Cristina Russ, The Flexible Quit Date Study Group

Journal Articles: Pulmonary & Critical Care Med

INTRODUCTION: Current smoking cessation guidelines recommend setting a quit date prior to starting pharmacotherapy. However, providing flexibility in the date of quitting may be more acceptable to some smokers. The objective of this study was to compare varenicline 1 mg twice daily (b.i.d.) with placebo in subjects using a flexible quit date paradigm after starting medication.

METHODS: In this double-blind, randomized, placebo-controlled international study, smokers of ≥10 cigarettes/day, aged 18-75 years, and who were motivated to quit were randomized (3:1) to receive varenicline 1 mg b.i.d. or placebo for 12 weeks. Subjects were followed up through Week 24. Subjects were …