Medicine and Health Sciences Commons^™

Commentary: Recognizing Pupillary Dysfunction In Diabetic Autonomic Neuropathy, Padmaja Sudhakar

Ophthalmology and Visual Science Faculty Publications

No abstract provided.

The Medicalization Of Sleeplessness: Results Of U.S. Office Visit Outcomes, 2008-2015, Mairead Eastin Moloney, Gabriele Ciciurkaite, Robyn Lewis Brown

Sociology Faculty Publications

Previous analysis of U.S. physician office visits (1993–2007) indicated that the medicalization of sleeplessness was on the rise and had potentially negative implications for population health. Our study asks if the medicalization of sleeplessness at the level of patient-physician interaction has persisted over time. Using the most recent years available (2008–2015) of the National Ambulatory Medical Care Survey we calculated nationally representative estimates for four sleeplessness-related outcomes of physician office visits: sleeplessness complaint, insomnia diagnosis, and prescription of benzodiazepine and non-benzodiazepine sedative-hypnotics (NBSH). To test for the significance of the linear trajectory, we ran a series of bivariate linear models. …

The Late Stage Of Copi Vesicle Fission Requires Shorter Forms Of Phosphatidic Acid And Diacylglycerol, Seung-Yeol Park, Jia-Shu Yang, Zhen Li, Pan Deng, Xiaohong Zhu, David Young, Maria Ericsson, Ruben L. H. Andringa, Adriaan J. Minnaard, Chunmei Zhu, Fei Sun, D. Branch Moody, Andrew J. Morris, Jun Fan, Victor W. Hsu

Internal Medicine Faculty Publications

Studies on vesicle formation by the Coat Protein I (COPI) complex have contributed to a basic understanding of how vesicular transport is initiated. Phosphatidic acid (PA) and diacylglycerol (DAG) have been found previously to be required for the fission stage of COPI vesicle formation. Here, we find that PA with varying lipid geometry can all promote early fission, but only PA with shortened acyl chains promotes late fission. Moreover, diacylglycerol (DAG) acts after PA in late fission, with this role of DAG also requiring shorter acyl chains. Further highlighting the importance of the short-chain lipid geometry for late fission, we …

Equine Arteritis Virus Long-Term Persistence Is Orchestrated By Cd8+ T Lymphocyte Transcription Factors, Inhibitory Receptors, And The Cxcl16/Cxcr6 Axis, Mariano Carossino, Pouya Dini, Theodore S. Kalbfleisch, Alan T. Loynachan, Igor F. Canisso, R. Frank Cook, Peter J. Timoney, Udeni B. R. Balasuriya

Veterinary Science Faculty Publications

Equine arteritis virus (EAV) has the unique ability to establish long-term persistent infection in the reproductive tract of stallions and be sexually transmitted. Previous studies showed that long-term persistent infection is associated with a specific allele of the CXCL16 gene (CXCL16S) and that persistence is maintained despite the presence of local inflammatory and humoral and mucosal antibody responses. Here, we performed transcriptomic analysis of the ampullae, the primary site of EAV persistence in long-term EAV carrier stallions, to understand the molecular signatures of viral persistence. We demonstrated that the local CD8⁺ T lymphocyte response is predominantly orchestrated …

Targeting Pathogenic Lafora Bodies In Lafora Disease Using An Antibody-Enzyme Fusion, M. Kathryn Brewer, Annette M. Uittenbogaard, Grant L. Austin, Dyann M. Segvich, Anna Depaoli-Roach, Peter J. Roach, John J. Mccarthy, Zoe R. Simmons, Jason A. Brandon, Zhengqiu Zhou, Jill Zeller, Lyndsay E. A. Young, Ramon C. Sun, James R. Pauly, Nadine M. Aziz, Bradley L. Hodges, Tracy R. Mcknight, Dustin D. Armstrong, Matthew S. Gentry

Molecular and Cellular Biochemistry Faculty Publications

Lafora disease (LD) is a fatal childhood epilepsy caused by recessive mutations in either the EPM2A or EPM2B gene. A hallmark of LD is the intracellular accumulation of insoluble polysaccharide deposits known as Lafora bodies (LBs) in the brain and other tissues. In LD mouse models, genetic reduction of glycogen synthesis eliminates LB formation and rescues the neurological phenotype. Therefore, LBs have become a therapeutic target for ameliorating LD. Herein, we demonstrate that human pancreatic α-amylase degrades LBs. We fused this amylase to a cell-penetrating antibody fragment, and this antibody-enzyme fusion (VAL-0417) degrades LBs in vitro and dramatically reduces LB …

Main And Regional Campus Assessments Of Applicants To A Rural Physician Leadership Program: A Generalizability Analysis, Terry D. Stratton, Clarence Kreiter, Carol L. Elam

Behavioral Science Faculty Publications

While the selection of qualified applicants often relies, in part, on scores generated from a medical school pre-admission interview (MSPI), the growth of regional medical campuses (RMCs) – many with specialized rural tracks, programs, or missions – has challenged schools to accommodate a wider range of stakeholder input. This study examines the reliabilities of main (urban) and regional (rural) campus interviewers’ assessments of applicants to a Rural Physician Leadership Program (RPLP) located in the southeastern United States.

Data from RPLP applicants completing MSPIs on two campuses from 2009-2017 (n = 232) were examined in a generalizability analysis. In two separate …

White Matter Hyperintensity Regression: Comparison Of Brain Atrophy And Cognitive Profiles With Progression And Stable Groups, Omar M. Al-Janabi, Christopher E. Bauer, Larry B. Goldstein, Richard R. Murphy, Ahmed A. Bahrani, Charles D. Smith, Donna M. Wilcock, Brian T. Gold, Gregory A. Jicha

Sanders-Brown Center on Aging Faculty Publications

Subcortical white matter hyperintensities (WMHs) in the aging population frequently represent vascular injury that may lead to cognitive impairment. WMH progression is well described, but the factors underlying WMH regression remain poorly understood. A sample of 351 participants from the Alzheimer’s Disease Neuroimaging Initiative 2 (ADNI2) was explored who had WMH volumetric quantification, structural brain measures, and cognitive measures (memory and executive function) at baseline and after approximately 2 years. Selected participants were categorized into three groups based on WMH change over time, including those that demonstrated regression (n = 96; 25.5%), stability (n = 72; 19.1%), and …

Distinct Patterns Of Default Mode And Executive Control Network Circuitry Contribute To Present And Future Executive Function In Older Adults, Christopher A. Brown, Frederick A. Schmitt, Charles D. Smith, Brian T. Gold

Neuroscience Faculty Publications

Executive function (EF) performance in older adults has been linked with functional and structural profiles within the executive control network (ECN) and default mode network (DMN), white matter hyperintensities (WMH) burden and levels of Alzheimer's disease (AD) pathology. Here, we simultaneously explored the unique contributions of these factors to baseline and longitudinal EF performance in older adults. Thirty-two cognitively normal (CN) older adults underwent neuropsychological testing at baseline and annually for three years. Neuroimaging and AD pathology measures were collected at baseline. Separate linear regression models were used to determine which of these variables predicted composite EF scores at baseline …

Managing Intracranial Hemorrhage In Patients With A Durable Continuous Flow Left Ventricular Assist Device, Godly Jack, Phil Barker, Ryan Searcy, Jason N. Katz

The VAD Journal

Background: While intracranial hemorrhage (ICH) is a known complication of left ventricular assist device (LVAD) support, and is associated with high morbidity and mortality, optimal care pathways have neither been elucidated nor reported. We describe management of LVAD patients following ICH, with a focus on anticoagulation, operative interventions, care team designation, complications, and outcomes.

Methods: We retrospectively reviewed all durable continuous-flow LVAD implantations at our academic medical center from January 2007 to July 2018. Patients who experienced ICH after LVAD were identified. We defined baseline and ICH characteristics, medical and surgical interventions, care teams, and outcomes including death, device thrombosis, …

Ccr3 Inhibition For Ocular Angiogenesis And Macular Degeneration, Jayakrishna Ambati

Ophthalmology and Visual Science Faculty Patents

Provided are methods and compositions for the treatment or prevention of ocular angiogenesis and neovascularization. Administration of inhibitors of the CCR3 receptor or its ligands eotaxin (CCL11), eotaxin-2 (CCL24) or eotaxin-3 (CCL26) inhibits ocular angiogenesis.

A Legacy Of Disease, Arthur L. Frank

Journal of Appalachian Health

In Appalachia, like much of America, there are important health issues that have not always been appropriately predicted or dealt with when they occur. Lifestyle issues in Appalachia lead to obesity and heart disease, not surprisingly due to extensive use of sugary drinks. The current opioid crisis could have been better predicted given the trauma of mining and the past abuse of less-potent narcotics. A continuing major problem in the whole country is inadequate support for preventive health activities.

Using Mini-Grants To Build Multi-Sector Partnerships In Rural Tennessee, Ginny Kidwell, Kristine Bowers, Taylor M. Dula, Randolph F. Wykoff

Journal of Appalachian Health

Rural counties in Tennessee, including those located in Appalachia, face some of the greatest health challenges in the nation. Unpublished data collated by the East Tennessee State University College of Public Health (ETSU) show that Tennessee’s 52 Appalachian counties vary dramatically from its 43 non-Appalachian counties in virtually all socioeconomic, behavioral, and health outcome metrics. Since 2011, the Tennessee Institute of Public Health (TNIPH) has actively encouraged local communities to address behavior change, enhance educational achievement, and improve economic conditions as essential components for improving health and well-being in rural Tennessee.

Improving Access To Addiction Recovery Care In Central Appalachia Through Organizational Collaboration, Katy Stigers

Journal of Appalachian Health

Fahe, a Network of 50+ members throughout Appalachia based in Berea KY, has brought together a coalition to finance, build, and manage several addiction recovery care centers across Kentucky and West Virginia, increase access to employment, and deploy vouchers for supportive services.

Disparities In Quality Of Life By Appalachian-Designation Among Women With Breast Cancer, Robin C. Vanderpool, Ann L. Coker, Heather M. Bush, Sarah E. Cprek

Journal of Appalachian Health

Introduction: Few studies have examined the association of geography and quality of life (QOL) among breast cancer patients, particularly differences between Appalachian and non-Appalachian Kentucky women, which is important given the cancer and socioeconomic disparities present in Appalachia.

Purpose: The purpose of this study was to determine whether women with breast cancer residing in Appalachian Kentucky experience poorer health outcomes in regards to depression, stress, QOL, and spiritual wellbeing, relative to those living in non-Appalachian Kentucky after adjusting for demographic, socioeconomic, and health-related factors.

Methods: Women, aged 18–79, recruited from the Kentucky Cancer Registry between 2009 and 2013 with an …

Social Media Use Among Nonprofit Organizations In Rural Appalachia, Mckenzie Liegel, Jodi L. Southerland, Katie Baker

Journal of Appalachian Health

Introduction: Social media have changed the landscape of health communication for nonprofit organizations (NPOs). Yet, adoption and use of social media lag among NPOs in rural Appalachia due largely to limited infrastructure development.

Methods: Semi-structured phone interviews were conducted in January–March 2018 with 21 NPO representatives in an 8-county region of rural Appalachian Tennessee. NPO representatives were asked questions pertaining to social media use and message content, effective communication strategies, and best practices in social media use. Transcripts were analyzed in April–May 2018 using thematic analysis.

Results: The majority of NPOs had a Facebook page and recognized its …

Barriers To Healthy Eating Among High School Youth In Rural Southern Appalachia, Jodi L. Southerland, Taylor M. Dula, Deborah L. Slawson

Journal of Appalachian Health

Introduction: Diet and nutrition play an important role in a child’s health and reduce the risk of numerous health problems including obesity. Dietary habits can be difficult to modify in children, particularly in Appalachia, where access to affordable, healthy foods is limited.

Purpose: To examine barriers to healthy eating among Appalachian youth.

Methods: In 2013–2014, data were gathered via focus groups and interviews from parents, school personnel, and adolescents (N=99) in six counties across southern Appalachia. Data were analyzed using thematic network analysis. Analysis was completed in 2015.

Results: Participants identified multiple barriers to healthy eating among adolescents. Barriers comprised …

West Virginia’S Sugary Drink Tax: Examining Print Media Frames In Local News Sources, Lauri Andress, Ogaga Urhie, Christine Compton

Journal of Appalachian Health

Introduction: Framing is an important aspect of the policy process that helps the public and decision makers sort through and resolve highly charged claims about an issue. Through slight changes in the presentation of issues, a framing effect may alter public support. The way a proposed sugary drink tax is discussed in public discourse and by the media significantly influences policy acceptance. Given the public health significance of obesity and diabetes in West Virginia (WV) the study of media frames employed to represent a sugary drink tax policy is useful.

Methods: Using quantitative content analysis, this study assessed news articles—published …

Investigating The Impact Of The Diseases Of Despair In Appalachia, Michael Meit, Megan Heffernan, Erin Tanenbaum

Journal of Appalachian Health

Introduction: Appalachia is one of the regions most significantly impacted by the opioid crisis. This study investigated mortality due to diseases of despair within the Appalachian Region, with an additional focus on deaths attributable to opioid overdose.

Methods: Diseases of despair include: alcohol, prescription drug and illegal drug overdose, suicide, and alcoholic liver disease/cirrhosis of the liver. Mortality data from the National Center for Health Statistics (NCHS) National Vital Statistics System (NVSS) Multiple Cause of Death database were analyzed for this study, focusing on individuals aged 15–64.

Results: Over the past two decades, the mortality rate due to diseases of …

Root Causes Of Appalachia’S Deaths Of Despair, F. Douglas Scutchfield Md

Journal of Appalachian Health

The U.S. is experiencing a decline in life expectancy, particularly among rural white males in their most productive years. Appalachia is disproportionally represented in mortality rates, accounting for 30% of the U.S. population, but 50% of the excess mortality attributed to the “deaths of despair”: drug overdose, suicide, and alcoholic cirrhosis. A substantial proportion of that excess mortality is related to the current opioid crisis we are experiencing. We have data on evidence-based solutions to the treatment of addiction, but little information on prevention of addiction as well as the other deaths of despair, likely with the same etiologic agent. …

Graft Within A Graft Endoluminal Graft, David J. Minion

Surgery Faculty Patents

A segmented endograft includes at least one positioning segment and at least one main body segment which are separately deployable. The at least one positioning segment and at least one main body segment may be connected one to another. For example, the at least one positioning segment and at least one main body segment may be connected along a portion of a circumference thereof, but unconnected along a remainder of the circumference thereof. The at least one positioning segment overlaps a portion of the at least one main body segment. Deployment systems may include the segmented endograft and the segmented …

Reporter's Occupation And Source Of Adverse Device Event Reports Contained In The Fda's Maude Database, Kevin T. Kavanagh, Raeford E. Brown, Steve S. Kraman, Lindsay E. Calderon, Sean P. Kavanagh

Anesthesiology Faculty Publications

Introduction: A review of the medical device adverse events submitted to the United States Food & Drug Administration (FDA) Manufacturer and User Facility Device Experience (MAUDE) database was undertaken to determine the major sources of the information.

Methods: The reporter’s occupation and source of the medical device report were determined for acquisition dates Jan 1, 1997 to Dec 31, 2018. A total of 7,766,737 adverse event records were analyzed.

Results: 96.6% of reports originated with the manufacturer. Patients (patients/family/friend) were the most frequent submitter of reports directly to the FDA, almost five times as often as physicians. Nurses submitted reports …

Neurocognitive Basis Of Repetition Deficits In Primary Progressive Aphasia, Sladjana Lukic, Maria Luisa Mandelli, Ariane Welch, Kesshi Jordan, Wendy Shwe, John Neuhaus, Zachary Miller, H. Isabel Hubbard, Maya Henry, Bruce L. Miller, Nina F. Dronkers, Maria Luisa Gorno-Tempini

Communication Sciences and Disorders Faculty Publications

Previous studies indicate that repetition is affected in primary progressive aphasia (PPA), particularly in the logopenic variant, due to limited auditory-verbal short-term memory (avSTM). We tested repetition of phrases varied by length (short, long) and meaning (meaningful, non-meaningful) in 58 participants (22 logopenic, 19 nonfluent, and 17 semantic variants) and 21 healthy controls using a modified Bayles repetition test. We evaluated the relation between cortical thickness and repetition performance and whether sub-scores could discriminate PPA variants.

Logopenic participants showed impaired repetition across all phrases, specifically in repeating long phrases and any phrases that were non-meaningful. Nonfluent, semantic, and healthy control …

Key Mechanisms By Which Post-Icu Activities Can Improve In-Icu Care: Results Of The International Thrive Collaboratives, Kimberley J. Haines, Carla M. Sevin, Elizabeth Hibbert, Leanne M. Boehm, Krishna Aparanji, Rita N. Bakhru, Anthony J. Bastin, Sarah J. Beesley, Brad W. Butcher, Kelly Drumright, Tammy L. Eaton, Thomas Farley, Penelope Firshman, Andrew Fritschle, Clare Holdsworth, Aluko A. Hope, Annie Johnson, Michael T. Kenes, Babar A. Khan, Janet A. Kloos, Erin K. Kross, Belinda J. Macleod-Smith, Pamela Mactavish, Joel Meyer, Ashley Montgomery-Yates, Tara Quasim, Howard L. Saft, Andrew Slack, Joanna Stollings, Gerald Weinhouse

Internal Medicine Faculty Publications

Objective: To identify the key mechanisms that clinicians perceive improve care in the intensive care unit (ICU), as a result of their involvement in post-ICU programs.

Methods: Qualitative inquiry via focus groups and interviews with members of the Society of Critical Care Medicine’s THRIVE collaborative sites (follow-up clinics and peer support). Framework analysis was used to synthesize and interpret the data.

Results: Five key mechanisms were identified as drivers of improvement back into the ICU: (1) identifying otherwise unseen targets for ICU quality improvement or education programs—new ideas for quality improvement were generated and greater attention paid to detail in …

Quantitative Systems Pharmacology Model Of Chimeric Antigen Receptor T-Cell Therapy, Deni Hardiansyah, Chee Meng Ng

Pharmaceutical Sciences Faculty Publications

Chimeric antigen receptor T‐cell (CART) therapy is a new and promising cancer therapy. However, severe toxicity due to cytokine release syndrome (CRS) in CART‐treated patients highlighted the possible danger of this new therapy. Disease burden and CART doses are the potential factors associated with CRS but the detail relationships between these factors and the severity of the CRS remain largely unknown. In this study, the quantitative systems pharmacology (QSP) approach is used to quantify the complex relationships among CART doses, disease burden, and pro inflammatory cytokines in human subjects and to gain relevant insights into the determinant of clinical toxicity/efficacy …

A Technique For Approximating Transition Rates From Published Survival Analyses, Markian A. Pahuta, Joel Werier, Eugene K. Wai, Roy A. Patchell, Doug Coyle

Neurology Faculty Publications

Background: Quality-adjusted-life-years (QALYs) are used to concurrently quantify morbidity and mortality within a single parameter. For this reason, QALYs can facilitate the discussion of risks and benefits during patient counseling regarding treatment options. QALYs are often calculated using partitioned-survival modelling. Alternatively, QALYs can be calculated using more flexible and informative state-transition models populated with transition rates estimated using multistate modelling (MSM) techniques. Unfortunately the latter approach is considered not possible when only progression-free survival (PFS) and overall survival (OS) analyses are reported.

Methods: We have developed a method that can be used to estimate approximate transition rates from published PFS …

Racial And Ethnic Disparities In Stroke Outcomes: A Scoping Review Of Post-Stroke Disability Assessment Tools, Suzanne Perea Burns, Brandi M. White, Gayenell Magwood, Charles Ellis, Ayaba Logan, Joy N. Jones Buie, Robert J. Adams

Health and Clinical Sciences Faculty Publications

Purpose: To identify how post-stroke disability outcomes are assessed in studies that examine racial/ethnic disparities and to map the identified assessment content to the International Classification of Functioning, Disability, and Health (ICF) across the time course of stroke recovery.

Methods: We conducted a scoping review of the literature. Articles published between January 2001 and July 2017 were identified through Scopus, PubMed, CINAHL, and PsycINFO according to predefined inclusion and exclusion criteria.

Results: We identified 1791 articles through database and hand-searching strategies. Of the articles, 194 met inclusion criteria for full-text review, and 41 met inclusion criteria for study inclusion. The …

Prevalence And Correlates Of Diagnosed And Undiagnosed Hypertension In The Indigenous Kuna Population Of Panamá, Daniel R. Hanna, Rebekah J. Walker, Brittany L. Smalls, Jennifer A. Campbell, Aprill Z. Dawson, Leonard E. Egede

Center for Health Services Research Faculty Publications

Background: To determine the prevalence of hypertension and investigate sociodemographic correlates in an indigenous Kuna community living on the San Blas islands of Panama.

Methods: Data was collected from adults using a paper-based survey using a cross sectional study design. Blood pressure was measured, and hypertension defined at two cut-points: 130/80 mmHg and 140/90 mmHg. Individuals with undiagnosed hypertension had a blood pressure measurement that indicated hypertension, however, the individual had not been told by a doctor they had hypertension. Whereas individuals with diagnosed hypertension had been told by a healthcare provider that they had hypertension. Univariate tests compared diagnosed …

The Role Of The Community Health Delivery System In The Health And Well-Being Of Justice-Involved Women: A Narrative Review, Sharla A. Smith, Glen P. Mays, Tracie C. Collins, Megha Ramaswamy

Health Management and Policy Faculty Publications

Background: Over seven million imprisoned and jailed women are released into the community each year and many are ill-equipped to meet the challenges of re-integration. Upon release into their community, women are faced with uncertain barriers and challenges using community services to improve their health and well-being and reuniting with families. Few studies have identified and described the barriers of the community health delivery system (CHDS)- a complex set of social, justice, and healthcare organizations that provide community services aimed to improve the health and well-being (i.e. safety, health, the success of integration, and life satisfaction) of justice-involved women. We …

Phospholipases D: Making Sense Of Redundancy And Duplication, Andrew J. Morris

Internal Medicine Faculty Publications

Why have two genes when one would suffice? Evolutionary pressure means that biology, unlike government, is generally intolerant of wasted effort. Therefore, when multiple genes exist presumably they are there to provide some benefit to the organism even if that benefit is not immediately obvious to us scientists. A recent report from Raghu and colleagues (Biosci. Rep. (2018) 38, pii: BSR20181690) [1] sheds some light on one possible reason for the existence of two Phospholipases D genes in chordates when only one is present in invertebrates.

Microrna Regulation Of Epigenetic Modifiers In Breast Cancer, Brock Humphries, Zhishan Wang, Chengfeng Yang

Toxicology and Cancer Biology Faculty Publications

Epigenetics refers to the heritable changes in gene expression without a change in the DNA sequence itself. Two of these major changes include aberrant DNA methylation as well as changes to histone modification patterns. Alterations to the epigenome can drive expression of oncogenes and suppression of tumor suppressors, resulting in tumorigenesis and cancer progression. In addition to modifications of the epigenome, microRNA (miRNA) dysregulation is also a hallmark for cancer initiation and metastasis. Advances in our understanding of cancer biology demonstrate that alterations in the epigenome are not only a major cause of miRNA dysregulation in cancer, but that miRNAs …