Translational Medical Research Commons^™

Developing A Community-Based Screening And Referral Mechanism For Atrial Fibrillation In Low Resource Settings: “Smartphone Monitoring For Atrial Fibrillation In Real-Time – India (Smart-India)”, Apurv Soni, Nisha Fahey, Harshil Patel, Kandarp Talati, Anna Handorf, John A. Bostrom, Shyamsundar Raihatha, Ravi Shah, Sunil Karna, Robert J. Goldberg, Jeroan J. Allison, Ki Chon, Somashekhar M. Nimbalkar, David D. Mcmanus

Apurv Soni

BACKGROUND: Atrial fibrillation (AF), the world’s most common arrhythmia, often goes undetected and untreated in low-resource communities, including India. Moreover, AF is an important risk factor for stroke, which plagues an estimated 1.6 million Indians annually. As such, early detection of AF and management of high-risk patients is critically important to decrease stroke burden in individuals with AF.

OBJECTIVE: The objectives of this study are to evaluate the age- and sex-stratified epidemiology of AF in Anand District, Gujarat India; characterize the profile of individuals who are diagnosed with AF; and determine the performance of two mobile technologies for community-based AF …

High Burden Of Unrecognized Atrial Fibrillation In Rural India: An Innovative Community-Based Cross-Sectional Screening Program, Apurv Soni, Allison Earon, Anna Handorf, Nisha Fahey, Kandarp Talati, John Bostrom, Ki Chon, Craig Napolitano, Michael S. Chin, John Stephen Sullivan, Shyamsundar Raithatha, Robert J. Goldberg, Somashekhar Nimbalkar, Jeroan J. Allison, Sunil Thanvi, David D. Mcmanus

Apurv Soni

BACKGROUND: Atrial fibrillation, the world's most common arrhythmia, is a leading risk factor for stroke, a disease striking nearly 1.6 million Indians annually. Early detection and management of atrial fibrillation is a promising opportunity to prevent stroke but widespread screening programs in limited resource settings using conventional methods is difficult and costly.

OBJECTIVE: The objective of this study is to screen people for atrial fibrillation in rural western India using a US Food and Drug Administration-approved single-lead electrocardiography device, Alivecor.

METHODS: Residents from 6 villages in Anand District, Gujarat, India, comprised the base population. After obtaining informed consent, a team …

Hepatic Changes Associated With Chronic Alcohol Exposure In An Alpha-1 Antitrypsin Piz Mouse Model, Zhuoyao Lyu, Alisha M. Gruntman, Brian O'Sullivan-Murphy, Christian Mueller, Terence R. Flotte

Christian Mueller

The PiZ mutation in the alpha-1 antitrypsin (AAT) gene causes the PiZ mutant protein to be sequestered in the endoplasmic reticulum of hepatocytes, causing significant liver pathology in ~10% of PiZZ homozygous AAT disease patients. Current transgenic mouse models of the disease include the liver-specific over-expression of mutant PiZ protein. However, these animal models do not efficiently recapitulate the liver damage found in PiZZ homozygous patients. Since only a small percentage of patients develop liver disease and it is not reproducible in animal models of AATD, it suggests that there are other factors that participate in disease pathogenesis. Here, we …

Evolution Of The Alpha-1 Antitrypsin Muscle Gene Therapy: Translation From Clinical Trial To Benchtop And Back Again, Alisha M. Gruntman, Gwladys Gernoux, Gensheng Wang, Janet Benson, Jeff Chulay, Dave Knop, Christian Mueller, Terence R. Flotte

Christian Mueller

Alpha-one antitrypsin (AAT) deficiency is a genetic disease affecting the lungs due to inadequate anti-protease activity in the pulmonary interstitium. On-going human trials use intra-muscular delivery of adeno-associated virus (rAAV1), allowing expressing myofibers to secrete normal (M)AAT protein. In the Phase IIa trial, patients in the highest dose cohort (6x1012vg/kg) were given 100 intra-muscular (IM) injections of undiluted vector, with serum AAT levels still substantially below target levels. Previous work has shown that delivering rAAV vector to the musculature via limb perfusion leads to widespread gene expression in myofibers. We hypothesize that widespread delivery would result in an overall increase …

Pain And Pharmacologic Pain Management In Long-Stay Nursing Home Residents, Jacob N. Hunnicutt, Christine M. Ulbricht, Jennifer Tjia, Kate L. Lapane

Jennifer Tjia

Prior studies estimate that >40% of long-stay nursing home (NH) residents experience persistent pain, with 20% of residents in pain receiving no analgesics. Strengthened NH surveyor guidance and improved pain measures on the Minimum Data Set (MDS) 3.0 were introduced in March 2009 and October 2010, respectively. This study aimed to provide estimates after these important initiatives of: 1) prevalence and correlates of persistent pain; and 2) prevalence and correlates of untreated or undertreated persistent pain. We identified 1,387,405 long-stay residents in United States NHs between 2011-2012 with 2 MDS assessments 90 days apart. Pain was categorized as persistent (pain …

Magnitude Of And Prognostic Factors Associated With 1-Year Mortality After Hospital Discharge For Acute Decompensated Heart Failure Based On Ejection Fraction Findings, Andrew H. Coles, Mayra Tisminetzky, Jorge L. Yarzebski, Darleen M. Lessard, Joel M. Gore, Chad E. Darling, Robert J. Goldberg

Jorge L. Yarzebski

BACKGROUND: Limited data exist about the magnitude of and the factors associated with prognosis within 1 year for patients discharged from the hospital after acute decompensated heart failure. Data are particularly limited from the more generalizable perspective of a population-based investigation and should be further stratified according to currently recommended ejection fraction (EF) findings.

METHODS AND RESULTS: The hospital medical records of residents of the Worcester, Massachusetts, metropolitan area who were discharged after acute decompensated heart failure from all 11 medical centers in central Massachusetts during 1995, 2000, 2002, 2004, and 2006 were reviewed. The average age of the 4025 …

Plasma Micrornas Are Associated With Atrial Fibrillation (The Mirhythm Study) And Change After Catheter-Ablation, David D. Mcmanus, Kahraman Tanriverdi, Honghuang Lin, Nada Esa, Menhel Kinno, Rosalind Lee, Divakar Mandapati, Stanley Tam, Patrick T. Ellinor, John F. Keaney, Emelia J. Benjamin, Victor R. Ambros, Jane E. Freedman

Victor R. Ambros

Background: Atrial fibrillation (AF) is the most common dysrhythmia in the U.S. and Europe. Few biomarkers exist to identify individuals at risk for AF. Cardiac microRNAs (miRNAs) have been implicated in susceptibility to AF and are detectable in the circulation. Nevertheless, data are limited on how circulating levels of miRNAs relate to AF or change over time after catheter- ablation. Methods: In 211 miRhythm participants (112 with paroxysmal or persistent AF; 99 without AF), we quantified plasma expression of 86 miRNAs associated with cardiac remodeling or disease by high-throughput quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR). We used qRT-PCR to examine …

Increased Number Of Circulating Exosomes And Their Microrna Cargos Are Potential Novel Biomarkers In Alcoholic Hepatitis, Fatemeh Momen-Heravi, Banishree Saha, Karen Kodys, Donna Catalano, Abhishek Satishchandran, Gyongyi Szabo

Gyongyi Szabo

BACKGROUND: It has been well documented that alcohol and its metabolites induce injury and inflammation in the liver. However, there is no potential biomarker to monitor the extent of liver injury in alcoholic hepatitis patients. MicroRNAs (miRNAs) are a class of non-coding RNAs that are involved in various physiologic and pathologic processes. In the circulation, a great proportion of miRNAs is associated with extracellular vesicles (EVs)/exosomes. Here, we hypothesized that the exosome-associated miRNAs can be used as potential biomarkers in alcoholic hepatitis (AH).

METHODS: Exosomes were isolated from sera of alcohol-fed mice or pair-fed mice, and plasma of alcoholic hepatitis …

Progression Of Non-Alcoholic Steatosis To Steatohepatitis And Fibrosis Parallels Cumulative Accumulation Of Danger Signals That Promote Inflammation And Liver Tumors In A High Fat-Cholesterol-Sugar Diet Model In Mice, Michal Ganz, Terence N. Bukong, Timea Csak, Banishree Saha, Jin-Kyu Park, Aditya Ambade, Karen Kodys, Gyongyi Szabo

Gyongyi Szabo

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is becoming a pandemic. While multiple 'hits' have been reported to contribute to NAFLD progression to non-alcoholic steatohepatitis (NASH), fibrosis and liver cancer, understanding the natural history of the specific molecular signals leading to hepatocyte damage, inflammation and fibrosis, is hampered by the lack of suitable animal models that reproduce disease progression in humans. The purpose of this study was first, to develop a mouse model that closely mimics progressive NAFLD covering the spectrum of immune, metabolic and histopathologic abnormalities present in human disease; and second, to characterize the temporal relationship between sterile/exogenous danger …

Expert–Novice Differences In Mental Models Of Viruses, Vaccines, And The Causes Of Infectious Disease, Benjamin D. Jee, David H. Uttal, Amy N. Spiegel, Judy Diamond

Amy N. Spiegel

Humans are exposed to viruses everywhere they live, play, and work. Yet people’s beliefs about viruses may be confused or inaccurate, potentially impairing their understanding of scientific information. This study used semi-structured interviews to examine people’s beliefs about viruses, vaccines, and the causes of infectious disease. We compared people at different levels of science expertise: middle school students, teachers, and professional virologists. The virologists described more entities involved in microbiological processes, how these entities behaved, and why. Quantitative and qualitative analyses revealed distinctions in the cognitive organization of several concepts, including infection and vaccination. For example, some students and teachers …

Gene Expression Profiles Identify Features Common To Lobular And Ductal Premalignant Breast Lesions, Amy L. Roberts, D. Joseph Jerry, Kelly J. Gauger, Sallie S. Schneider, Giovanna M. Crisi, Grace Makari-Judson, Ashraf Khan, Karl Simin

Grace Makari-Judson MD

Premalignant lesions have been identified in both the ductal and lobular units of the breast epithelium. These lesions have a 4-fold increase in risk of progression to invasive breast cancer, but 80% will remain indolent. This may be due, in part, to the uncertainty of diagnoses as inter-observer reproducibility is poor. When treated with prophylactic hormone therapies blocking the estrogen receptor, up to 40% of women still develop tumors. Therefore the challenge is to develop diagnostic tests that identify the subset of high-risk lesions and provide appropriate prophylactic therapies. We undertook genome-wide expression studies to define sets of genes that …

Rodent Traumatic Brain Injury As A Model For Human Traumatic Axonal Damage And Neurodegeneration, Nils Henninger

Nils Henninger

Traumatic brain injury (TBI) is inherently heterogeneous with a complex underlying pathophysiology. Over the past decades many attempts have been undertaken to develop novel and innovative ways to mimic human aspects of TBI in rodents. This presentation will provide a brief overview of translationally relevant rodent TBI models with special emphasis on mild-to-moderate injuries and associated pathology.

Trends And Characteristics Associated With The Risk Of Re-Hospitalization In Patients Discharged From The Hospital After Acute Myocardial Infarction, Mayra Tisminetzky, Han-Yang Chen, Edgard A. Granillo, Joel M. Gore, Jorge L. Yarzebski, Darleen M. Lessard, Robert J. Goldberg

Jorge L. Yarzebski

BACKGROUND: Despite encouraging declines in short-term mortality in patients hospitalized with acute myocardial infarction (AMI), repeat hospitalizations among those discharged from the hospital after AMI remain a major clinical and public health concern. Few studies, however, have described the relatively contemporary magnitude, factors associated with, as well as decade long trends in repeat hospitalizations for cardiovascular disease (CVD) and other causes in patients discharged from the hospital after AMI. METHODS: We reviewed the medical records of 6,018 residents of the Worcester (MA) metropolitan area who were hospitalized for AMI in 6 biennial periods between 1999 and 2009. Re-hospitalizations for any …

Keynote Speaker Presentations: 5th Annual Umass Center For Clinical And Translational Research Retreat (Video), Robert H. Brown Jr., Thomas Grisso

Thomas Grisso

This video features the full keynote presentations from the 5th Annual UMass Center for Clinical and Translational Science Research Retreat at the University of Massachusetts Medical School (UMMS) in Worcester, MA, on May 20, 2014.

Beginning at 12:40

1st Keynote Speaker: Robert H. Brown, Jr., MD, D.Phil, Chair, Department of Neurology, UMMS. “Lou Gehrig Disease: From Mapping to Medicines”

Beginning at 1:22:19

2nd Keynote Speaker: Thomas Grisso, PhD, Director, Law and Psychiatry Program and Professor, Department of Psychiatry, UMMS. Recipient, Chancellor’s Medal for Distinguished Scholarship. “Translational Research in Law and Psychiatry”

Also included is a brief introductory presentation with updates …

Does Functional Gain And Pain Relief After Tkr And Thr Differ By Patient Obese Status?, Wenjun Li, Jeffrey Lange, Leslie R. Harrold, Jeroan J. Allison, Courtland Lewis, Thomas Bowen, David C. Ayers, Patricia D. Franklin

Jeroan J. Allison

Introduction: Obesity is an important predictor of functional status and pain after total knee (TKR) and total hip (THR) replacement. However, variations in pre-post TKR and THR changes in function and pain by obesity status remain to be examined.

Material & Methods: Pre- and 6 month post surgery data were collected on 2,964 primary TKR and 2,040 primary THR patients between 5/2011 and 3/2013. Data included demographics, comorbidities, operative joint pain severity based on the Knee Injury or Hip Disability and Osteoarthritis Outcome Score (KOOS/HOOS), WOMAC pain (higher is better), physical function (SF-36 PCS, higher is better), mental health (SF-36 …

Identification Of A Human Monoclonal Antibody To Replace Equine Diphtheria Anti-Toxin For The Treatment Of Diphtheria, Leila M. Sevigny, Brian J. Booth, Kirk J. Rowley, Brett A. Leav, Peter S. Cheslock, Kerry A. Garrity, Susan Sloan, Gregory J. Babcock, William D. Thomas, Mark Klempner, Yang Wang

William D Thomas Jr

Diphtheria anti-toxin (DAT) has been used to treat Corynebacterium diphtheriae infection for over one hundred years. While the global incidence of diphtheria has declined in the 20th century, the disease remains endemic in many parts of the world and significant outbreaks still occur. Diphtheria anti-toxin is an equine polyclonal antibody with considerable side effects that is in critically short supply globally. A safer, more readily available alternative to DAT would be desirable. In the current study, we cloned human monoclonal antibodies (HuMabs) directly from antibody secreting cells of human volunteers immunized with Td vaccine. We isolated a diverse panel of …

Therapeutic Approaches To Aggressive Carcinomas Based On A Novel Vegf/Neuropilin Autocrine Pathway, Hira Lal Goel, Arthur M. Mercurio

Arthur M. Mercurio

Summary: Autocrine VEGF signaling in tumor cells contributes to de-differentiation and function of tumor initiating/stem cells. NRP2 is the nexus of a signaling pathway that promotes de-differentiation and sustains tumor initiating/stem sells. Anti-NRP2 therapy is worth pursuing, especially for high-grade cancers. Therapeutic Abs are available. This presentation was part of the retreat mini-symposium entitled: Biomarker Discovery and Targeted Therapeutics in Cancer.

Statin Discontinuation Among Nursing Home Residents With Advanced Dementia, Jennifer Tjia, Sarah L. Cutrona, Daniel J. Peterson, Becky A. Briesacher

Jennifer Tjia

Background: Statin use in elderly individuals with life-limiting illness such as advanced dementia is controversial.

Objective: To describe factors associated with statin discontinuation and estimate impact of discontinuation on 28-day hospitalizations in nursing home (NH) residents with advanced dementia.

Methods: Retrospective cohort study of NH residents ≥ 65 years with recent progression to advanced dementia from 5 large U.S. states drawn from the 2007-2008 Minimum Data Set 2.0. We identified residents using statins. Clinical characteristics and 28-day hospitalization risk were compared for residents discontinuing and continuing statins. Multivariable Cox proportional hazard models identified factors associated with time to statin discontinuation …

Health Literacy And Cancer Prevention: It’S Not What You Say It’S What They Hear, Kathleen M. Mazor, Douglas W. Roblin, Andrew E. Williams, Paul J. K. Han, Mary E. Costanza, Sarah L. Cutrona, Terry S. Field, Bridget Gaglio, Joann L. Wagner, Brandi E. Robinson, Vinutha Vijayadeva

Mary E. Costanza

Background: A growing body of literature documents the relationship between health literacy and important health behaviors and outcomes. Most research to date has focused on print literacy–few studies have examined literacy with respect to spoken information (“spoken health literacy”). We sought to examine the extent to which responses to physician advice about cancer prevention and screening were associated with spoken health literacy.

Methods: Participants listened to 3 simulated physician-patient discussions addressing: 1) Prostate Specific Antigen (PSA) testing; 2) tamoxifen for breast cancer prevention; and 3) colorectal cancer (CRC) screening. The physician provided information on risks and benefits but did not …