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Genetic Modification Of Human Mesenchymal Stem Cells Helps To Reduce Adiposity And Improve Glucose Tolerance In An Obese Diabetic Mouse Model., Sabyasachi Sen, Cleyton C Domingues, Carol Rouphael, Cyril Chou, Chul Kim, Nagendra Yadava Dec 2015

Genetic Modification Of Human Mesenchymal Stem Cells Helps To Reduce Adiposity And Improve Glucose Tolerance In An Obese Diabetic Mouse Model., Sabyasachi Sen, Cleyton C Domingues, Carol Rouphael, Cyril Chou, Chul Kim, Nagendra Yadava

Medicine Faculty Publications

INTRODUCTION: Human mesenchymal stem cells (MSCs) are multipotent cells that can differentiate into fat, muscle, bone and cartilage cells. Exposure of subcutaneous abdominal adipose tissue derived AD-MSCs to high glucose (HG) leads to superoxide accumulation and up-regulation of inflammatory molecules. Our aim was to inquire how HG exposure affects MSCs differentiation and whether the mechanism is reversible.

METHODS: We exposed human adipose tissue derived MSCs to HG (25 mM) and compared it to normal glucose (NG, 5.5 mM) exposed cells at 7, 10 and 14 days. We examined mitochondrial superoxide accumulation (Mitosox-Red), cellular oxygen consumption rate (OCR, Seahorse) and gene …


Endothelin-B Receptor Activation In Astrocytes Regulates The Rate Of Oligodendrocyte Regeneration During Remyelination., Timothy R. Hammond, Brian Mcellin, Paul D Morton, Matthew Raymond, Jeff Dupree, Vittorio Gallo Nov 2015

Endothelin-B Receptor Activation In Astrocytes Regulates The Rate Of Oligodendrocyte Regeneration During Remyelination., Timothy R. Hammond, Brian Mcellin, Paul D Morton, Matthew Raymond, Jeff Dupree, Vittorio Gallo

Medicine Faculty Publications

Reactive astrogliosis is an essential and ubiquitous response to CNS injury, but in some cases, aberrant activation of astrocytes and their release of inhibitory signaling molecules can impair endogenous neural repair processes. Our lab previously identified a secreted intercellular signaling molecule, called endothelin-1 (ET-1), which is expressed at high levels by reactive astrocytes in multiple sclerosis (MS) lesions and limits repair by delaying oligodendrocyte progenitor cell (OPC) maturation. However, as ET receptors are widely expressed on neural cells, the cell- and receptor-specific mechanisms of OPC inhibition by ET-1 action remain undefined. Using pharmacological approaches and cell-specific endothelin receptor (EDNR) ablation, …


Enhanced Fitness And Renal Function In Type 2 Diabetes., Eric S. Nylen, S. M. Gandhi, Raya E. Kheirbek, Peter Kokkinos Oct 2015

Enhanced Fitness And Renal Function In Type 2 Diabetes., Eric S. Nylen, S. M. Gandhi, Raya E. Kheirbek, Peter Kokkinos

Medicine Faculty Publications

Aims

To investigate the renal effects of fitness in people with diabetes with mild renal dysfunction.

Methods

The effect of a 12-week exercise programme on estimated GFR in 128 people with diabetes was evaluated.

Results

All cardiometabolic variables improved after 12 weeks of supervised exercise. Although there was a modest 3.9% increase in estimated GFR from baseline in the 128 people who completed the study, those with baseline chronic kidney disease stages 2 and 3 were found to have significant (6 and 12%, respectively; p < 0.01) improvements in post-exercise estimated GFR. Moreover, 42% of the people with chronic kidney disease stage 3 improved to chronic kidney disease stage 2 after the intervention.

Conclusion

Short-term exercise improves renal function in those with more moderate baseline chronic kidney disease. …


New-Onset Diabetes Mellitus With Exposure To Ledipasvir And Sofosbuvir., Resmi Premji, Nira Roopnarinesingh, Nazia Qazi, Eric S. Nylen Oct 2015

New-Onset Diabetes Mellitus With Exposure To Ledipasvir And Sofosbuvir., Resmi Premji, Nira Roopnarinesingh, Nazia Qazi, Eric S. Nylen

Medicine Faculty Publications

The combination therapy of ledipasvir/sofosbuvir was approved by the Food and Drug Administration in 2014 for the treatment of chronic hepatitis C. Although hyperglycemia is not well known to occur with its use, we present 2 cases of new-onset diabetes mellitus and a review of the literature suggesting an adverse event association. In the first patient with HIV, we postulate that ledipasvir/sofosbuvir increased the levels of tenofovir and thereby potentiated hyperglycemia. In the second case of a patient with prediabetes, ledipasvir/sofosbuvir appeared to increase insulin resistance. A literature review further supported an association of hyperglycemia and the use of ledipasvir/sofosbuvir. …


Mantle Cell Lymphoma: Current Concepts, Manish K. Pant, Weaam Alshenawy, Ahmed Alrajjal, Hussain Alrobeh, Imad A. Tabbara Aug 2015

Mantle Cell Lymphoma: Current Concepts, Manish K. Pant, Weaam Alshenawy, Ahmed Alrajjal, Hussain Alrobeh, Imad A. Tabbara

Medicine Faculty Publications

Mantle Cell Lymphoma is a rare B-cell malignancy that can invade almost any structure in the body and recur after short-lived clinical responses. The pathogenesis and clinical features are well defined, but management has not yet been optimized. Induction with traditional immune-chemotherapy regimens that are used in other nonHodgkin lymphomas rarely generate durable remissions. Therefore, clinical research is needed to improve treatment of de novo disease and to establish safe and effective regimens for maintenance and salvage options for relapsed or refractory disease. This comprehensive review discusses disease pathogenesis and focuses on emerging treatment paradigms using novel targeted therapies.


Bioregulatory Systems Medicine: An Innovative Approach To Integrating The Science Of Molecular Networks, Inflammation, And Systems Biology With The Patient's Autoregulatory Capacity?, Alyssa W Goldman, Yvonne Burmeister, Konstantin Cesnulevicius, Martha Herbert, Mary Kane, David Lescheid, Timothy Mccaffrey, Myron Schultz, Bernd Seilheimer, Alta Smit, Georges St Laurent, Brian Berman Aug 2015

Bioregulatory Systems Medicine: An Innovative Approach To Integrating The Science Of Molecular Networks, Inflammation, And Systems Biology With The Patient's Autoregulatory Capacity?, Alyssa W Goldman, Yvonne Burmeister, Konstantin Cesnulevicius, Martha Herbert, Mary Kane, David Lescheid, Timothy Mccaffrey, Myron Schultz, Bernd Seilheimer, Alta Smit, Georges St Laurent, Brian Berman

Medicine Faculty Publications

Bioregulatory systems medicine (BrSM) is a paradigm that aims to advance current medical practices. The basic scientific and clinical tenets of this approach embrace an interconnected picture of human health, supported largely by recent advances in systems biology and genomics, and focus on the implications of multi-scale interconnectivity for improving therapeutic approaches to disease. This article introduces the formal incorporation of these scientific and clinical elements into a cohesive theoretical model of the BrSM approach. The authors review this integrated body of knowledge and discuss how the emergent conceptual model offers the medical field a new avenue for extending the …


Predicting Risk Of End-Stage Liver Disease In Antiretroviral-Treated Hiv/Hepatitis C Virus-Coinfected Patients, Vincent Lo Re Iii, Michael J. Kallan, Janet P. Tate, Joseph K. Lim, Matthew Bidwell Goetz, Cynthia L. Gibert, +10 Additional Authors Jul 2015

Predicting Risk Of End-Stage Liver Disease In Antiretroviral-Treated Hiv/Hepatitis C Virus-Coinfected Patients, Vincent Lo Re Iii, Michael J. Kallan, Janet P. Tate, Joseph K. Lim, Matthew Bidwell Goetz, Cynthia L. Gibert, +10 Additional Authors

Medicine Faculty Publications

Background. End-stage liver disease (ESLD) is an important cause of morbidity among HIV/hepatitis C virus (HCV)-coinfected patients. Quantifying the risk of this outcome over time could help determine which coinfected patients should be targeted for risk factor modification and HCV treatment. We evaluated demographic, clinical, and laboratory variables to predict risk of ESLD in HIV/HCV-coinfected patients receiving antiretroviral therapy (ART).

Methods. We conducted a retrospective cohort study among 6,016 HIV/HCV-coinfected patients who received ART within the Veterans Health Administration between 1997 and 2010. The main outcome was incident ESLD, defined by hepatic decompensation, hepatocellular carcinoma, or liver-related death. Cox regression …


Human Immunodeficiency Virus (Hiv) In Washington, D.C.: Prevalence Of Antiretroviral Resistance In Treatment Naïve Patients From 2007 To 2010, Matthew J. Swierzbinski, Virginia L. Kan, David M. Parenti Jun 2015

Human Immunodeficiency Virus (Hiv) In Washington, D.C.: Prevalence Of Antiretroviral Resistance In Treatment Naïve Patients From 2007 To 2010, Matthew J. Swierzbinski, Virginia L. Kan, David M. Parenti

Medicine Faculty Publications

HIV treatment has been greatly impacted by transmitted resistance to antiretrovirals (ARV). Several studies have documented resistance in naïve individuals and estimates of transmitted drug resistance mutations range from <5% to as high as 25%. Washington, D.C. has one of the highest human immunodeficiency virus (HIV) prevalence rates in the United States (3.2% in 2009), but local data regarding the frequency of major mutations and antiretroviral (ARV) resistance has been limited. Medical records of HIV positive, ARV-naïve adults at two facilities in Washington, D.C., The George Washington University Medical Center and the Veterans Affairs Medical Center, were retrospectively analyzed in subjects who had genotypic resistance testing from 2007 to 2010. Of 407 ARV-naïve patients, at least one transmitted drug resistance mutation was detected in 17% of our patients, with non-nucleoside reverse transcriptase (NNRTI) mutations observed in 15%. Among patients with at least one reverse transcriptase (RT) or major protease region (Pr) resistance mutation, 85% had resistance against a single ARV class. Dual and triple class resistance mutations were seen in 8 patients (2%) and 3 patients (0.7%), respectively. Most of the multiple class resistance was seen in 2010. A gradual increase in NNRTI resistance was noted during 2008 to 2010. Our prevalence of transmitted RT, major Pr mutations (17.4%) and ARV resistance (8.6%) were high but similar to rates reported by others within the United States. Given the high HIV prevalence in the District of Columbia, this has important implications for treatment of these ARV-naïve patients.


Race And Ethnicity, Obesity, Metabolic Health, And Risk Of Cardiovascular Disease In Postmenopausal Women, Michelle D. Schmiegelow, Haley Hedlin, Rachel H. Mackey, Lisa W. Martin, Mara Z. Vitolins, Marcia L. Stefanick, Marco V. Perez, Matthew Allison, Mark A. Hlatky May 2015

Race And Ethnicity, Obesity, Metabolic Health, And Risk Of Cardiovascular Disease In Postmenopausal Women, Michelle D. Schmiegelow, Haley Hedlin, Rachel H. Mackey, Lisa W. Martin, Mara Z. Vitolins, Marcia L. Stefanick, Marco V. Perez, Matthew Allison, Mark A. Hlatky

Medicine Faculty Publications

Background It is unclear whether obesity unaccompanied by metabolic abnormalities is associated with increased cardiovascular disease risk across racial and ethnic subgroups.

Methods and Results We identified 14 364 postmenopausal women from the Women's Health Initiative who had data on fasting serum lipids and serum glucose and no history of cardiovascular disease or diabetes at baseline. We categorized women by body mass index (in kg/m2) as normal weight (body mass index 18.5 to P=0.05). Obese black women without metabolic syndrome had higher adjusted risk (HR 1.95) than obese white women (HR 1.07; interaction P=0.02). Among women with …


Radium-223 For The Treatment Of Castration-Resistant Prostate Cancer, Joelle El-Amm, Jeanny B. Aragon-Ching May 2015

Radium-223 For The Treatment Of Castration-Resistant Prostate Cancer, Joelle El-Amm, Jeanny B. Aragon-Ching

Medicine Faculty Publications

The vast majority of patients with metastatic castration-resistant prostate cancer (mCRPC) develop bone metastases. Bone metastases are a source of significant morbidity and affect quality of life in these patients. Several bone-targeting agents are approved for the treatment of bone metastases in prostate cancer, including bisphosphonates, denosumab, and radiopharmaceuticals. Radium-223 is a novel first-in-class alpha-emitting radiopharmaceutical that has been approved for treatment of patients with mCRPC with bone metastases. Radium-223 delivers cytotoxic radiation to the sites of bone metastases and offers the advantage of minimal myelosuppression. The landmark Phase III ALSYMPCA trial demonstrated that, in addition to providing bone-related palliation, …


Investigation Of Sex Differences In The Expression Of Rora And Its Transcriptional Targets In The Brain As A Potential Contributor To The Sex Bias In Autism, Valerie W. Hu, Tewarit Sarachana, Rachel Sherrard, Kristen M. Kocher May 2015

Investigation Of Sex Differences In The Expression Of Rora And Its Transcriptional Targets In The Brain As A Potential Contributor To The Sex Bias In Autism, Valerie W. Hu, Tewarit Sarachana, Rachel Sherrard, Kristen M. Kocher

Medicine Faculty Publications

Background

Autism spectrum disorder (ASD) is a neurodevelopmental condition characterized by significant impairment in reciprocal social interactions and communication coupled with stereotyped, repetitive behaviors and restricted interests. Although genomic and functional studies are beginning to reveal some of the genetic complexity and underlying pathobiology of ASD, the consistently reported male bias of ASD remains an enigma. We have recently proposed that retinoic acid-related orphan receptor alpha (RORA), which is reduced in the brain and lymphoblastoid cell lines of multiple cohorts of individuals with ASD and oppositely regulated by male and female hormones, might contribute to the sex bias …


Association Between Inflammation And Cardiac Geometry In Chronic Kidney Disease: Findings From The Cric Study., Jayanta Gupta, Elizabeth Dominic, Jeffrey C. Fink, Akinlolu O. Ojo, Ian R. Barrows, Muredach Reilly, Raymond R. Townsend, Marshall Joffe, Sylvia Rosas, Melanie Wolman, Samir Patel, Martin Keane, Harold I. Feldman, John W. Kusek, Dominic S. Raj Apr 2015

Association Between Inflammation And Cardiac Geometry In Chronic Kidney Disease: Findings From The Cric Study., Jayanta Gupta, Elizabeth Dominic, Jeffrey C. Fink, Akinlolu O. Ojo, Ian R. Barrows, Muredach Reilly, Raymond R. Townsend, Marshall Joffe, Sylvia Rosas, Melanie Wolman, Samir Patel, Martin Keane, Harold I. Feldman, John W. Kusek, Dominic S. Raj

Medicine Faculty Publications

Background

Left ventricular hypertrophy (LVH) and myocardial contractile dysfunction are independent predictors of mortality in patients with chronic kidney disease (CKD). The association between inflammatory biomarkers and cardiac geometry has not yet been studied in a large cohort of CKD patients with a wide range of kidney function.

Methods

Plasma levels of interleukin (IL)-1β, IL-1 receptor antagonist (IL-1RA), IL-6, tumor necrosis factor (TNF)-α, transforming growth factor (TGF)-β, high-sensitivity C-Reactive protein (hs-CRP), fibrinogen and serum albumin were measured in 3,939 Chronic Renal Insufficiency Cohort study participants. Echocardiography was performed according to the recommendations of the American Society of Echocardiography and interpreted …


Translation Initiation Complex Eif4f Is A Therapeutic Target For Dual Mtor Kinase Inhibitors In Non-Hodgkin Lymphoma., Christos Demosthenous, Jing Jing Han, Mary J Stenson, Matthew J Maurer, Linda E Wellik, Brian Link, Kristen Hege, Ahmet Dogan, Eduardo Sotomayor, Thomas Witzig, Mamta Gupta Apr 2015

Translation Initiation Complex Eif4f Is A Therapeutic Target For Dual Mtor Kinase Inhibitors In Non-Hodgkin Lymphoma., Christos Demosthenous, Jing Jing Han, Mary J Stenson, Matthew J Maurer, Linda E Wellik, Brian Link, Kristen Hege, Ahmet Dogan, Eduardo Sotomayor, Thomas Witzig, Mamta Gupta

Medicine Faculty Publications

Deregulated mRNA translation has been implicated in disease development and in part is controlled by a eukaryotic initiation complex eIF4F (composed of eIF4E, eIF4G and eIF4A). We demonstrate here that the cap bound fraction from lymphoma cells was enriched with eIF4G and eIF4E indicating that lymphoma cells exist in an activated translational state. Moreover, 77% (110/142) of diffuse large B cell lymphoma tumors expressed eIF4E and this was associated with an inferior event free survival. Over-expression of wild-type eIF4E (eIF4E(WT)) but not cap-mutant eIF4E (eIF4E(cap mutant)) increased the activation of the eIF4F complex. Treatment with the active-site dual mTOR inhibitor …


True Durability: Hiv Virologic Suppression In An Urban Clinic And Implications For Timing Of Intensive Adherence Efforts And Viral Load Monitoring., Debra A Benator, Angelo Elmi, Manuel D Rodriguez, Howard B Gale, Virginia L. Kan, Heather J. Hoffman, Susan Tramazzo, Karen Hall, Angela Mcknight, Leah Squires Apr 2015

True Durability: Hiv Virologic Suppression In An Urban Clinic And Implications For Timing Of Intensive Adherence Efforts And Viral Load Monitoring., Debra A Benator, Angelo Elmi, Manuel D Rodriguez, Howard B Gale, Virginia L. Kan, Heather J. Hoffman, Susan Tramazzo, Karen Hall, Angela Mcknight, Leah Squires

Medicine Faculty Publications

Although the majority of HIV-infected patients who begin potent antiretroviral therapy should expect long-term virologic suppression, the realities in practice are less certain. Durability of viral suppression was examined to define the best timing of targeted adherence strategies and intensive viral load monitoring in an urban clinic population with multiple challenges to ART adherence. We examined the risk of viral rebound for patients who achieved two consecutive viral loads lower than the lower limit of quantification (LLOQ) within 390 days. For 791 patients with two viral loads below the LLOQ, viral rebound >LLOQ from the first viral load was 36.9 …


The Predictive Value Of Current Haemoglobin Levels For Incident Tuberculosis And/Or Mortality During Long-Term Antiretroviral Therapy In South Africa: A Cohort Study, Andrew D. Kerkhoff, Robin Wood, Frank G. Cobelens, Ankur Gupta-Wright, Linda-Gail Bekker, Stephen D. Lawn Apr 2015

The Predictive Value Of Current Haemoglobin Levels For Incident Tuberculosis And/Or Mortality During Long-Term Antiretroviral Therapy In South Africa: A Cohort Study, Andrew D. Kerkhoff, Robin Wood, Frank G. Cobelens, Ankur Gupta-Wright, Linda-Gail Bekker, Stephen D. Lawn

Medicine Faculty Publications

Background

Low haemoglobin concentrations may be predictive of incident tuberculosis (TB) and death in HIV-infected patients receiving antiretroviral therapy (ART), but data are limited and inconsistent. We examined these relationships retrospectively in a long-term South African ART cohort with multiple time-updated haemoglobin measurements.

Methods

Prospectively collected clinical data on patients receiving ART for up to 8 years in a community-based cohort were analysed. Time-updated haemoglobin concentrations, CD4 counts and HIV viral loads were recorded, and TB diagnoses and deaths from all causes were ascertained. Anaemia severity was classified using World Health Organization criteria. TB incidence and mortality rates were calculated …


A Six-Week Home Exercise Program Improves Endothelial Function And Cd34+ Circulating Progenitor Cells In Patients With Pre-Diabetes, Sabyasachi Sen, Sarah Witkowski, Ann Lagoy, Ashequl Islam Apr 2015

A Six-Week Home Exercise Program Improves Endothelial Function And Cd34+ Circulating Progenitor Cells In Patients With Pre-Diabetes, Sabyasachi Sen, Sarah Witkowski, Ann Lagoy, Ashequl Islam

Medicine Faculty Publications

Background: Pre-diabetes is associated with endothelial dysfunction and affects endothelium-associated stem cells. Lifestyle modification has been shown to prevent the progression from pre-diabetes to overt type 2 diabetes; however, the effect of such interventions on CD34+ progenitor cells in pre-diabetes participants has not been tested. The purpose of this study was to determine whether a home-based 6-week exercise intervention improved vascular function, circulating number, function, and gene expression of circulating CD34+progenitor cells in patients with pre-diabetes.

Methods: Patients (40 - 70 years, BMI of 25 - 39.9, n = 11) were enrolled in a 16-week randomized crossover …


True Durability: Hiv Virologic Suppression In An Urban Clinic And Implications For Timing Of Intensive Adherence Efforts And Viral Load Monitoring, Debra A. Benator, Angelo Elmi, Manuel D. Rodriguez, Howard B. Gale, Virginia L. Kan, Heather J. Hoffman, Susan Tramazzo, Karen Hall, Angela Mcknight, Leah Squires Apr 2015

True Durability: Hiv Virologic Suppression In An Urban Clinic And Implications For Timing Of Intensive Adherence Efforts And Viral Load Monitoring, Debra A. Benator, Angelo Elmi, Manuel D. Rodriguez, Howard B. Gale, Virginia L. Kan, Heather J. Hoffman, Susan Tramazzo, Karen Hall, Angela Mcknight, Leah Squires

Medicine Faculty Publications

Although the majority of HIV-infected patients who begin potent antiretroviral therapy should expect long-term virologic suppression, the realities in practice are less certain. Durability of viral suppression was examined to define the best timing of targeted adherence strategies and intensive viral load monitoring in an urban clinic population with multiple challenges to ART adherence. We examined the risk of viral rebound for patients who achieved two consecutive viral loads lower than the lower limit of quantification (LLOQ) within 390 days. For 791 patients with two viral loads below the LLOQ, viral rebound >LLOQ from the first viral load was 36.9 …


Relationship Of Physical Activity And Healthy Eating With Mortality And Incident Heart Failure Among Community-Dwelling Older Adults With Normal Body Mass Index, Ahmed Abdelmawgoud, Cynthia J. Brown, Xuemei Sui, Gregg C. Fonarow, Peter F. Kokkinos, Vera Bittner, Wilbert S. Aronow, Raya Kheirbek, Ross D. Fletcher, Steven N. Blair, Ali Ahmed Mar 2015

Relationship Of Physical Activity And Healthy Eating With Mortality And Incident Heart Failure Among Community-Dwelling Older Adults With Normal Body Mass Index, Ahmed Abdelmawgoud, Cynthia J. Brown, Xuemei Sui, Gregg C. Fonarow, Peter F. Kokkinos, Vera Bittner, Wilbert S. Aronow, Raya Kheirbek, Ross D. Fletcher, Steven N. Blair, Ali Ahmed

Medicine Faculty Publications

Aims

Normal body mass index (BMI) is associated with lower mortality and may be achieved by physical activity (PA), healthy eating (HE), or both. We examined the association of PA and HE with mortality and incident heart failure (HF) among 2040 community-dwelling older adults aged ≥ 65 years with baseline BMI 18.5 to 24.99 kg/m2 during 13 years of follow-up in the Cardiovascular Health Study.

Methods and results

Baseline PA was defined as ≥500 weekly metabolic equivalent task-minutes and HE as ≥5 daily servings of vegetable and fruit intake. Participants were categorized into four groups: (i) PA−/HE− (n …


Identifying State Resources And Support Programs On E-Government Websites For Persons With Intellectual And Developmental Disabilities, Kathleen M. Fisher, Justin D. Peterson, Jon D. Albert Mar 2015

Identifying State Resources And Support Programs On E-Government Websites For Persons With Intellectual And Developmental Disabilities, Kathleen M. Fisher, Justin D. Peterson, Jon D. Albert

Medicine Faculty Publications

This descriptive cross-sectional study identified resources and programs that are available nationwide on the Internet to support individuals and families with intellectual and developmental disabilities (I/DD), with a focus on intellectual disability. This evaluation included easily identifiable information on specific resources and highlighted unique programs found in individual states that were linked from e-government websites. Researchers documented the ease of access and available information for all 50 states and the District of Columbia. A number of disparities and areas for improvement were recorded for states and I/DD websites. The researchers conclude that a number of additional health and support services …


Effect Of Handoff Skills Training For Students During The Medicine Clerkship: A Quasi-Randomized Study, Juan A. Reyes, Larrie W. Greenberg, Richard L. Amdur, James Gehring, Linda Lesky Mar 2015

Effect Of Handoff Skills Training For Students During The Medicine Clerkship: A Quasi-Randomized Study, Juan A. Reyes, Larrie W. Greenberg, Richard L. Amdur, James Gehring, Linda Lesky

Medicine Faculty Publications

Continuity is critical for safe patient care and its absence is associated with adverse outcomes. Continuity requires handoffs between physicians, but most published studies of educational interventions to improve handoffs have focused primarily on residents, despite interns expected to being proficient. The AAMC core entrustable activities for graduating medical students includes handoffs as a milestone, but no controlled studies with students have assessed the impact of training in handoff skills. The purpose of this study was to assess the impact of an educational intervention to improve third-year medical student handoff skills, the durability of learned skills into the fourth year, …


Statin Use And Risk Of Haemorrhagic Stroke In A Community-Based Cohort Of Postmenopausal Women: An Observational Study From The Women's Health Initiative, Elena Salmoriago-Blotcher, Kathleen M. Hovey, Christopher A. Andrews, Jennifer G. Robinson, Karen C. Johnson, Sylvia Wassertheil-Smoller, Sybil Crawford, Lisa W. Martin, Judith Ockene, Joann E. Manson Feb 2015

Statin Use And Risk Of Haemorrhagic Stroke In A Community-Based Cohort Of Postmenopausal Women: An Observational Study From The Women's Health Initiative, Elena Salmoriago-Blotcher, Kathleen M. Hovey, Christopher A. Andrews, Jennifer G. Robinson, Karen C. Johnson, Sylvia Wassertheil-Smoller, Sybil Crawford, Lisa W. Martin, Judith Ockene, Joann E. Manson

Medicine Faculty Publications

Objectives To determine whether statin treatment is associated with increased risk of haemorrhagic stroke (HS) in older women. A secondary objective was to evaluate HS risk in users of combined statin and antiplatelet treatment.

Design Observational study: secondary data analysis from the Women's Health Initiative (WHI) clinical trials.

Setting Women were recruited from 40 participating sites.

Participants Cohort of 68 132 women followed through 2005 (parent study) and for an additional 5 years in the extension study.

Main outcome measures Statin use was assessed at baseline and at follow-up visits (1, 3, 6 and 9 years). Women brought medications in …


Report Of The Nih Task Force On Research Standards For Chronic Low Back Pain, Richard A. Deyo, Samuel F. Dworkin, Dagmar Amtmann, Gunnar Andersson, David G. Borenstein, +15 Additional Author Feb 2015

Report Of The Nih Task Force On Research Standards For Chronic Low Back Pain, Richard A. Deyo, Samuel F. Dworkin, Dagmar Amtmann, Gunnar Andersson, David G. Borenstein, +15 Additional Author

Medicine Faculty Publications

Abstract

Despite rapidly increasing intervention, functional disability due to chronic low back pain (cLBP) has increased in recent decades. We often cannot identify mechanisms to explain the major negative impact cLBP has on patients' lives. Such cLBP is often termed non-specific, and may be due to multiple biologic and behavioral etiologies. Researchers use varied inclusion criteria, definitions, baseline assessments, and outcome measures, which impede comparisons and consensus. The NIH Pain Consortium therefore charged a Research Task Force (RTF) to draft standards for research on cLBP. The resulting multidisciplinary panel recommended using 2 questions to define cLBP; classifying cLBP by its …


Transforming Health Professions' Education Through In-Country Collaboration: Examining The Consortia Between African Medical Schools Catalyzed By The Medical Education Partnership Initiative, Zohray Talib, Elsie Kiguli-Malwadde, Hannah Wohltjen, Millard Derbew, Yakub Mulla, David Olaleye, Nelson Sewankambo Jan 2015

Transforming Health Professions' Education Through In-Country Collaboration: Examining The Consortia Between African Medical Schools Catalyzed By The Medical Education Partnership Initiative, Zohray Talib, Elsie Kiguli-Malwadde, Hannah Wohltjen, Millard Derbew, Yakub Mulla, David Olaleye, Nelson Sewankambo

Medicine Faculty Publications

Background African medical schools have historically turned to northern partners for technical assistance and resources to strengthen their education and research programmes. In 2010, this paradigm shifted when the United States Government brought forward unprecedented resources to support African medical schools. The grant, entitled the Medical Education Partnership Initiative (MEPI) triggered a number of south-south collaborations between medical schools in Africa. This paper examines the goals of these partnerships and their impact on medical education and health workforce planning.

Methods Semistructured interviews were conducted with the Principal Investigators of the first four MEPI programmes that formed an in-country consortium. These …


Clinical Significance Of A Point Mutation In Dna Polymerase Beta (Polb) Gene In Gastric Cancer., Xiaohui Tan, Hongyi Wang, Guangbin Luo, Shuyang Ren, Wenmei Li, Jiantao Cui, Harindarpal S. Gill, Sidney W. Fu, Youyong Lu Jan 2015

Clinical Significance Of A Point Mutation In Dna Polymerase Beta (Polb) Gene In Gastric Cancer., Xiaohui Tan, Hongyi Wang, Guangbin Luo, Shuyang Ren, Wenmei Li, Jiantao Cui, Harindarpal S. Gill, Sidney W. Fu, Youyong Lu

Medicine Faculty Publications

Gastric cancer (GC) is a major cause of global cancer mortality. Genetic variations in DNA repair genes can modulate DNA repair capability and, consequently, have been associated with risk of developing cancer. We have previously identified a T to C point mutation at nucleotide 889 (T889C) in DNA polymerase beta (POLB) gene, a key enzyme involved in base excision repair in primary GCs. The purpose of this study was to evaluate the mutation and expression of POLB in a larger cohort and to identify possible prognostic roles of the POLB alterations in GC. Primary GC specimens and their matched normal …


Genes Required For Survival In Microgravity Revealed By Genome-Wide Yeast Deletion Collections Cultured During Spaceflight, Corey Nislow, Anna Y. Lee, Patricia L. Allen, Guri Giaever, Andrew Smith, Marinella Gebbia, Louis S. Stodieck, Jeffrey S. Hammond, Holly H. Birdsall, Timothy R. Hammond Jan 2015

Genes Required For Survival In Microgravity Revealed By Genome-Wide Yeast Deletion Collections Cultured During Spaceflight, Corey Nislow, Anna Y. Lee, Patricia L. Allen, Guri Giaever, Andrew Smith, Marinella Gebbia, Louis S. Stodieck, Jeffrey S. Hammond, Holly H. Birdsall, Timothy R. Hammond

Medicine Faculty Publications

Spaceflight is a unique environment with profound effects on biological systems including tissue redistribution and musculoskeletal stresses. However, the more subtle biological effects of spaceflight on cells and organisms are difficult to measure in a systematic, unbiased manner. Here we test the utility of the molecularly barcoded yeast deletion collection to provide a quantitative assessment of the effects of microgravity on a model organism. We developed robust hardware to screen, in parallel, the complete collection of ~4800 homozygous and ~5900 heterozygous (including ~1100 single-copy deletions of essential genes) yeast deletion strains, each carrying unique DNA that acts as strain identifiers. …


Clinical Significance Of A Point Mutation In Dna Polymerase Beta (Polb) Gene In Gastric Cancer., Xiaohui Tan, Hongyi Wang, Guangbin Luo, Shuyang Ren, Wenmei Li, Jiantao Cui, Harindarpal S. Gill, Sidney W. Fu, Youyong Lu Jan 2015

Clinical Significance Of A Point Mutation In Dna Polymerase Beta (Polb) Gene In Gastric Cancer., Xiaohui Tan, Hongyi Wang, Guangbin Luo, Shuyang Ren, Wenmei Li, Jiantao Cui, Harindarpal S. Gill, Sidney W. Fu, Youyong Lu

Medicine Faculty Publications

Gastric cancer (GC) is a major cause of global cancer mortality. Genetic variations in DNA repair genes can modulate DNA repair capability and, consequently, have been associated with risk of developing cancer. We have previously identified a T to C point mutation at nucleotide 889 (T889C) in DNA polymerase beta (POLB) gene, a key enzyme involved in base excision repair in primary GCs. The purpose of this study was to evaluate the mutation and expression of POLB in a larger cohort and to identify possible prognostic roles of the POLB alterations in GC. Primary GC specimens and their matched normal …


Integrating Spirituality As A Key Component Of Patient Care, Suzette Bremault-Phillips, Joanne Olson, Pamela Brett-Maclean, Doreen Oneschuk, Shane Sinclair, Ralph Magnus, Jeanne Weis, Marjan Abbasi, Jasneet Parmar, Christina M. Puchalski Jan 2015

Integrating Spirituality As A Key Component Of Patient Care, Suzette Bremault-Phillips, Joanne Olson, Pamela Brett-Maclean, Doreen Oneschuk, Shane Sinclair, Ralph Magnus, Jeanne Weis, Marjan Abbasi, Jasneet Parmar, Christina M. Puchalski

Medicine Faculty Publications

Patient care frequently focuses on physical aspects of disease management, with variable attention given to spiritual needs. And yet, patients indicate that spiritual suffering adds to distress associated with illness. Spirituality, broadly defined as that which gives meaning and purpose to a person’s life and connectedness to the significant or sacred, often becomes a central issue for patients. Growing evidence demonstrates that spirituality is important in patient care. Yet healthcare professionals (HCPs) do not always feel prepared to engage with patients about spiritual issues. In this project, HCPs attended an educational session focused on using the FICA Spiritual History Tool …


Cardiac Metabolomics And Autopsy In A Patient With Early Diffuse Systemic Sclerosis Presenting With Dyspnea: A Case Report, Tracy M. Frech, Monica P. Revelo, John J. Ryan, Ami A. Shah, Jessica Gordon, Victoria K. Shanmugam, +11 Additional Authors Jan 2015

Cardiac Metabolomics And Autopsy In A Patient With Early Diffuse Systemic Sclerosis Presenting With Dyspnea: A Case Report, Tracy M. Frech, Monica P. Revelo, John J. Ryan, Ami A. Shah, Jessica Gordon, Victoria K. Shanmugam, +11 Additional Authors

Medicine Faculty Publications

Introduction Diffuse systemic sclerosis is associated with high mortality; however, the pathogenesis of cardiac death in these patients is not clear.

Case presentation A 56-year-old Caucasian female patient presented with dyspnea and requested to donate her body to science in order to improve understanding of diffuse systemic sclerosis pathogenesis. She had extensive testing for dyspnea including pulmonary function tests, an echocardiogram, cardiac magnetic resonance imaging, and right heart catheterization to characterize her condition. Her case highlights the morbidity seen in this disease, including the presence of extensive skin thickening, digital ulcerations, and scleroderma renal crisis.

Conclusion In this case report, …


Feasibility Of Focused Cardiac Ultrasound In Pre-Participation Screening, Miriam L. Fishman, Jennifer Shea, Brian G. Choi, Allen J. Solomon Jan 2015

Feasibility Of Focused Cardiac Ultrasound In Pre-Participation Screening, Miriam L. Fishman, Jennifer Shea, Brian G. Choi, Allen J. Solomon

Medicine Faculty Publications

Objective: Current American Heart Association (AHA) guidelines for pre-participation athletic screening recommend a 12-point history and exam to minimize the risk of sudden cardiac death. We tested the hypothesis that focused cardiac ultrasound (FCU) performed and simultaneously interpreted by a cardiologist using a handheld ultrasound device would be a feasible addition. Methods: We performed pre-participation screening according to AHA recommendations on high school athletes in a multi-purpose room at their school. In addition to the standard 12-point assessment, a cardiologist simultaneously performed and interpreted a FCU on each athlete using a handheld ultrasound. Results: The mean age of the athletes …


Reactivation Of Latent Hiv-1 Provirus Via Targeting Protein Phosphatase-1., Mudit Tyagi, Sergey Iordanskiy, Tatyana Ammosova, Namita Kumari, Kahli Smith, + 9 More Jan 2015

Reactivation Of Latent Hiv-1 Provirus Via Targeting Protein Phosphatase-1., Mudit Tyagi, Sergey Iordanskiy, Tatyana Ammosova, Namita Kumari, Kahli Smith, + 9 More

Medicine Faculty Publications

BACKGROUND:

HIV-1 escapes antiretroviral drugs by integrating into the host DNA and forming a latent transcriptionally silent HIV-1 provirus. This provirus presents the major hurdle in HIV-1 eradication and cure. Transcriptional activation, which is prerequisite for reactivation and the eradication of latent proviruses, is impaired in latently infected T cells due to the lack of host transcription factors, primarily NF-κB and P-TEFb (CDK9/cyclin T1). We and others previously showed that protein phosphatase-1 (PP1) regulates HIV-1 transcription by modulating CDK9 phosphorylation. Recently we have developed a panel of small molecular compounds targeting a non-catalytic site of PP1.

RESULTS:

Here we generated …