Medicine and Health Sciences Commons^™

Operation Change Comes To Rural Appalachia, Keisha Hudson, Frances J. Feltner, Beth Bowling, Rose Gonzalez

Center of Excellence in Rural Health Presentations

Operation Change Model

Target Population: Underserved females age 45 and older who are experiencing obesity, joint pain, and limited mobility

An 18-week community-based behavioral health program that integrates:

• structured physical activity
• culturally tailored education
• motivational interviewer-led discussions to identify and address barriers to positive change

Appalachian Research Day: Come Sit On The Porch [2019], Frances J. Feltner, Melissa Slone, Beth Bowling

Center of Excellence in Rural Health Presentations

Rural Appalachian communities in eastern Kentucky suffer from some of the Nation’s most concerning health disparities. Community-based research can be an effective way to address health disparities by identifying problems and sharing workable solutions. However, challenges exist in recruiting and retaining research participants in rural populations that can often be difficult to reach. Partnerships between researchers and communities are essential to the success of the research process, particularly translation of findings back into the community.

The Importance Of Shared Language In Rural Behavioral Health Interventions: An Exploratory Linguistic Analysis, Michele Staton, Jennifer Cramer, Robert Walker, Claire Snell-Rood, Athena Kheibari

Behavioral Science Faculty Publications

A focus on the use of shared language to enhance congruence in interventionist-client dialogue is missing from traditional research on evidence-based practices and rural behavioral health. This study incorporates qualitative interactional sociolinguistics, which includes discourse analysis (typically written or audio recordings of face-to-face encounters with 11 clients and a study interventionist), to describe those speech patterns in a broad sense (dialect), as well as more specific use of communicative strategies to increase parity in the interaction between a rural interventionist delivering an evidence-based practice in the context of a research study with rural women opioid users in a non-therapeutic context. …

Child And Parent Perceptions Of Participating In Multimethod Research In The Acute Aftermath Of Pediatric Injury, Christine Kindler, Nancy Kassam-Adams, Tia Borger, Meghan L. Marsac

Pediatrics Faculty Publications

Background:

Despite growing evidence that participation in psychological trauma research is well tolerated by children and parents, ethics boards may voice concerns regarding research with families with recent acute trauma exposure. Factors impacting child and parent experiences of research participation are not well documented, particularly for methodologies including observational components.

Objectives:

This study describes child and parent perceptions of research participation involving an observational task following an acute traumatic event and explores potential relationships between research experience and selected demographic factors (race/ethnicity, sex, age, prior trauma exposure), and post-traumatic stress symptoms.

Methods:

As part of a larger study on the …

A Comprehensive Rehabilitation Program For Treating Lateral Elbow Tendinopathy, Joseph M. Day, Ann M. Lucado, Timothy L. Uhl

Physical Therapy Faculty Publications

Scapular muscle weakness in patients with lateral elbow tendinopathy is an identified impairment and is part of a multimodal rehabilitation approach. The published literature provides little information regarding specific rehabilitation guidelines that address both the proximal scapular muscle weakness and local elbow/ wrist dysfunctions common in patients with lateral elbow tendinopathy. The purpose of this clinical commentary is to describe a comprehensive rehabilitation strategy for individuals with lateral elbow tendinopathy. This program emphasizes a phased therapeutic strategy that addresses proximal and local dysfunction along the kinetic chain. This clinical protocol is currently being tested for efficacy as part of a …

Multiple Sclerosis Outcomes After Cancer Immunotherapy, Catherine R. Garcia, Rani Jayswal, Val R. Adams, Lowell B. Anthony, John L. Villano

Markey Cancer Center Faculty Publications

INTRODUCTION: Neurological immune-related adverse events are a rare but potentially deadly complication after immune checkpoint inhibitor (ICI) treatment. As multiple sclerosis (MS) is an immune-mediated disease, it is unknown how ICI treatment may affect outcomes.

METHODS: We analyzed the United States Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) database for pembrolizumab, atezolizumab, nivolumab, ipilimumab, avelumab, and durvalumab 2 years prior their FDA approval until December 31, 2017, to include all cases with confirmed diagnosis/relapse of MS. We also included cases reported in the literature and a patient from our institution.

RESULTS: We identified 14 cases of MS …

Why We Can’T Solve The Opioid Problem, Wayne F. Coombs, Ph.D.

Journal of Appalachian Health

Appalachia’s opioid epidemic is a complex, systemic problem being addressed by limited intervention processes conceptualized through narrow disciplinary models that are not working. We need a new comprehensive, collaborative approach if we ever hope to find solutions to this problem.

A Virginia Mountain City Responds To The Challenge Of Improving Health Outcomes, Robert S. Cowell Jr.

Journal of Appalachian Health

In 2012, Roanoke Virginia was becoming a city of haves and have-nots, a place where many were benefitting from revitalization underway but too many were seeing their situation grow worse and becoming even more entrenched. Poverty with levels as high as 50% in some neighborhoods; life expectancy sometimes 14 years shorter than those living just one or two neighborhoods over; and lack of access to fresh food, medical care, and economic opportunities—all within view of the largest hospital in the region was unacceptable.

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Adult Food Security And The Relationship With Adverse Childhood Experiences Among Residents Of Appalachian North Carolina, Manan Roy, Erin Bouldin, Maggie Bennett, Adam Hege

Journal of Appalachian Health

Introduction: The Appalachian region has worse health outcomes than the remainder of the United States. These disparities are often linked to the underlying social and environmental determinants of health. Adverse childhood experiences (ACEs) are associated with poor health outcomes across the lifespan and have a significant impact on future social determinants as an adult, including food security status.

Purpose: To explore the relationships between ACEs and food security among adults in the Appalachian counties of North Carolina and make comparisons with the rest of the state.

Methods: Researchers used North Carolina’s 2012 Behavioral Risk Factor Surveillance System data; namely, …

A Comparison Of Appalachian And Non-Appalachian Kentucky Dui Offenders, Megan F. Dickson, Megan Kissel, J. Matthew Webster

Journal of Appalachian Health

Background: Driving under the influence has been an overlooked consequence of the opioid epidemic. Although recent reports have highlighted the increased prevalence of DUI in rural communities and the extensive mental health problems and criminal and drug use histories among rural Appalachian DUI offenders, it is unclear how Appalachian DUI populations compare to DUI offenders in other regions.

Purpose: To help fill this void in the literature, the current study uses a statewide sample to examine how Appalachian DUI offenders differ from non-Appalachian DUI offenders in a predominantly rural state.

Methods: Assessment records were examined for 11,640 Kentucky DUI offenders …

Roanoke's Collective Public Health Activities, Michael Lytton

Journal of Appalachian Health

Roanoke is addressing problems that confront many small and medium sized cities in the U.S., especially disparities in health and life expectancy between neighborhoods. These disparities are often legacies of decades of racial and economic segregation, resulting in low-income or disinvested communities. Typically, such neighborhoods have fewer parks, higher vacancy rates and less stable affordable housing stock, inadequate public transit systems, too few clinics, too many fast food restaurants and insufficient access to high quality schools. In Roanoke these are the northwest and southeast quadrants, both federally designated Medically Underserved Areas, and characterized by a large proportion of the city’s …

Metformin Blunts Muscle Hypertrophy In Response To Progressive Resistance Exercise Training In Older Adults: A Randomized, Double-Blind, Placebo-Controlled, Multicenter Trial: The Masters Trial, R. Grace Walton, Cory M. Dungan, Douglas E. Long, S. Craig Tuggle, Kate Kosmac, Bailey D. Peck, Heather M. Bush, Alejandro G. Villasante Tezanos, Gerald Mcgwin, Samuel T. Windham, Fernando Ovalle, Marcas M. Bamman, Philip A. Kern, Charlotte A. Peterson

Clinical and Translational Science Faculty Publications

Progressive resistance exercise training (PRT) is the most effective known intervention for combating aging skeletal muscle atrophy. However, the hypertrophic response to PRT is variable, and this may be due to muscle inflammation susceptibility. Metformin reduces inflammation, so we hypothesized that metformin would augment the muscle response to PRT in healthy women and men aged 65 and older. In a randomized, double-blind trial, participants received 1,700 mg/day metformin (N = 46) or placebo (N = 48) throughout the study, and all subjects performed 14 weeks of supervised PRT. Although responses to PRT varied, placebo gained more lean body …

Metformin Blunts Muscle Hypertrophy In Response To Progressive Resistance Exercise Training In Older Adults: A Randomized, Double‐Blind, Placebo‐Controlled, Multicenter Trial: The Masters Trial, R. Grace Walton, Cory M. Dungan, Douglas E. Long, S. Craig Tuggle, Kate Kosmac, Bailey D. Peck, Heather M. Bush, Alejandro G. Villasante Tezanos, Gerald Mcgwin, Samuel T. Windham, Fernando Ovalle, Marcas M. Bamman, Philip A. Kern, Charlotte A. Peterson

Center for Muscle Biology Faculty Publications

Progressive resistance exercise training (PRT) is the most effective known intervention for combating aging skeletal muscle atrophy. However, the hypertrophic response to PRT is variable, and this may be due to muscle inflammation susceptibility. Metformin reduces inflammation, so we hypothesized that metformin would augment the muscle response to PRT in healthy women and men aged 65 and older. In a randomized, double-blind trial, participants received 1,700 mg/day metformin (N = 46) or placebo (N = 48) throughout the study, and all subjects performed 14 weeks of supervised PRT. Although responses to PRT varied, placebo gained more lean body …

The Effects Of Opioids On Kentucky's Workforce, Michael W. Clark, Jenny A. Minier, Charles J. Courtemanche, Bethany L. Paris, Michael T. Childress

CBER Research Report

From the executive summary:

Opioid abuse represents a significant and growing public health issue for both the nation and Kentucky. In 2016, opioids contributed to more than 62,000 deaths nationally and 1,406 deaths in Kentucky. National studies have placed the societal costs of opioid abuse at $55.7 billion in 2007 and $78.5 billion in 2013 (Birbaum et al. (2011) and Florence et al. (2016)). These costs included increased health care expenditures, higher criminal justice costs, and lost earnings due to reduced employment and premature deaths. The While House Council of Economic Advisors (2017) estimated the societal costs of opioid abuse …

Antisense Oligonucleotide Modulators Of Serotonin Receptor 2c And Uses Thereof, Stefan Stamm, Manli Shen, Serene Josiah

Molecular and Cellular Biochemistry Faculty Patents

The present invention provides, among other things, oligonucleotide modulators of human 5′-HT2C receptor (HTR2C) and improved methods and composition for treating HTR2C-related diseases, disorders or conditions based on such modulators. In particular, oligonucleotides modulators according to the invention target specific regions in the Exon V/Intron V junction of the human HTR2C pre-mRNA and drive expression of HTR2C Vb splice isoform, leading to increased generation of non-edited strong HTR2C receptor and enhanced serotonin receptor activity.

Imatinib Mesylate Effects On Zebrafish Reproductive Success: Gonadal Development, Gamete Quality, Fertility, Embryo-Larvae Viability And Development, And Related Genes, Nader Ahmadi, Seyed-Mohammadreza Samaee, Robert A. Yokel, Aliasghar Tehrani

Pharmaceutical Sciences Faculty Publications

Imatinib (IM) is a tyrosine kinase (TK) inhibitor (TKI) used to treat chronic myeloid leukemia. Clinical case reports and a few laboratory mammal studies provide inconclusive evidence about its deleterious effects on reproduction. The aim of the current study was to evaluate the potential of zebrafish to characterize IM-induced effects on reproduction and clarify IM effects on reproductive success. To this end, we exposed adult zebrafish to four concentrations of IM for 30 days followed by a 30-day depuration period. IM exposure caused a concentration-dependent, irreversible, suppression of folliculogenesis, reversible decrease in sperm density and motility, decreased fecundity and fertility, …

The Effect Of Smoking On Kentucky’S Workforce, Michael W. Clark, Jenny A. Minier, Charles J. Courtemanche, Bethany L. Paris, Michael T. Childress

CBER Research Report

Excerpt from the Executive Summary:

Smoking has been estimated to increase health care costs in the United States by $167.5 billion annually (Xu et al. 2015). In Kentucky, smoking adds $2.5 billion in health care expenditures each year. Most of these costs were paid by public programs such as Medicaid and Medicare. While these costs are significant, they represent only a portion of the costs that smoking imposes on society. Smoking also leads to poorer labor market outcomes. Smokers are more likely to be unemployed, earn lower wages, and die prematurely than non-smokers. These negative labor market effects reduce economic …

Altered Gating Of KV1.4 In The Nucleus Accumbens Suppresses Motivation For Reward, Bernadette O'Donovan, Adewale Adeluyi, Erin L Anderson, Robert D. Cole, Jill R. Turner, Pavel I. Ortinski

Neuroscience Faculty Publications

Deficient motivation contributes to numerous psychiatric disorders, including withdrawal from drug use, depression, schizophrenia, and others. Nucleus accumbens (NAc) has been implicated in motivated behavior, but it remains unclear whether motivational drive is linked to discrete neurobiological mechanisms within the NAc. To examine this, we profiled cohorts of Sprague-Dawley rats in a test of motivation to consume sucrose. We found that substantial variability in willingness to exert effort for reward was not associated with operant responding under low-effort conditions or stress levels. Instead, effort-based motivation was mirrored by a divergent NAc shell transcriptome with differential regulation at potassium and dopamine …

Fatty Acid Metabolites Combine With Reduced Β Oxidation To Activate Th17 Inflammation In Human Type 2 Diabetes, Dequina A. Nicholas, Elizabeth A. Proctor, Madhur Agrawal, Anna C. Belkina, James M. Van Nostrand, Leena Panneerseelan-Bharath, Albert R. Jones Iv, Forum Raval, Blanche C. Ip, Min Zhu, Jose M. Cacicedo, Chloe Habib, Nestor Sanez-Rueda, Leah Persky, Patrick G. Sullivan, Barbara E. Corkey, Caroline M. Apovian, Philip A. Kern, Douglas A. Lauffenburger, Barbara S. Nikolajczyk

Clinical and Translational Science Faculty Publications

Mechanisms that regulate metabolites and downstream energy generation are key determinants of T cell cytokine production, but the processes underlying the Th17 profile that predicts the metabolic status of people with obesity are untested. Th17 function requires fatty acid uptake, and our new data show that blockade of CPT1A inhibits Th17-associated cytokine production by cells from people with type 2 diabetes (T2D). A low CACT:CPT1A ratio in immune cells from T2D subjects indicates altered mitochondrial function and coincides with the preference of these cells to generate ATP through glycolysis rather than fatty acid oxidation. However, glycolysis was not critical for …

Extracellular Vesicle-Mediated Macrophage Activation: An Insight Into The Mechanism Of Thioredoxin-Mediated Immune Activation, Chontida Yarana, Hannah Thompson, Luksana Chaiswing, D. Allan Butterfield, Heidi L. Weiss, Subbarao Bondada, Sara S. Alhakeem, Suriyan Sukati, Daret K. St. Clair

Toxicology and Cancer Biology Faculty Publications

Extracellular vesicles (EVs) generated from redox active anticancer drugs are released into the extracellular environment. These EVs contain oxidized molecules and trigger inflammatory responses by macrophages. Using a mouse model of doxorubicin (DOX)-induced tissue injury, we previously found that the major sources of circulating EVs are from heart and liver, organs that are differentially affected by DOX. Here, we investigated the effects of EVs from cardiomyocytes and those from hepatocytes on macrophage activation. EVs from H9c2 rat cardiomyocytes (H9c2 EVs) and EVs from FL83b mouse hepatocytes (FL83 b EVs) have different levels of protein-bound 4-hydroxynonenal and thus different immunostimulatory effects …

Diabetes-Related Amylin Dyshomeostasis: A Contributing Factor To Cerebrovascular Pathology And Dementia, Han Ly, Florin Despa

Pharmacology and Nutritional Sciences Faculty Publications

Type 2 diabetes (T2D) increases the risk for cerebrovascular disease (CVD) and dementia. The underlying molecular mechanisms remain elusive, which hampers the development of treatment or/and effective prevention strategies. Recent studies suggest that dyshomeostasis of amylin, a satiety hormone that forms pancreatic amyloid in patients with T2D, promotes accumulation of amylin in cerebral small blood vessels and interaction with Alzheimer's disease (AD) pathology. Overexpression of human amylin in rodents (rodent amylin does not form amyloid) leads to late-life onset T2D and neurologic deficits. In this Review, we discuss clinical evidence of amylin pathology in CVD and AD and identify critical …

Flecainide Toxicity Resulting In Pacemaker Latency And Intermittent Failure To Capture, John M. Suffredini, Joshua Rutland, Peter Akpunonu, Regan Baum, John Catanzaro, Claude S. Elayi

Emergency Medicine Faculty Publications

BACKGROUND Flecainide is a class Ic antiarrhythmic agent used in the treatment of supraventricular and ventricular arrhythmias. It is associated with a potent adverse effect profile; however, the effects of flecainide toxicity in the setting of a pacemaker have not been well described. We describe a unique case of flecainide toxicity secondary to acute kidney injury in the setting of a dual-chamber pacemaker, resulting in ventricular capture latency and intermittent failure to capture.

CASE REPORT The patient was a 91-year-old female with a history of atrial fibrillation maintained in sinus rhythm on flecainide, who presented complaining of purple visual disturbances …

Assessing General Cognitive And Adaptive Abilities In Adults With Down Syndrome: A Systematic Review, Sarah Hamburg, Bryony Lowe, Carla Marie Startin, Concepcion Padilla, Antonia Coppus, Wayne Silverman, Juan Fortea, Shahid Zaman, Elizabeth Head, Benjamin L. Handen, Ira Lott, Weihong Song, André Strydom

Sanders-Brown Center on Aging Faculty Publications

BACKGROUND: Measures of general cognitive and adaptive ability in adults with Down syndrome (DS) used by previous studies vary substantially. This review summarises the different ability measures used previously, focusing on tests of intelligence quotient (IQ) and adaptive behaviour (AB), and where possible examines floor effects and differences between DS subpopulations. We aimed to use information regarding existing measures to provide recommendations for individual researchers and the DS research community.

RESULTS: Nineteen studies reporting IQ test data met inclusion for this review, with 17 different IQ tests used. Twelve of these IQ tests were used in only one study while …

Staying Out: Reentry Protective Factors Among Rural Women Offenders, Michele Staton, Megan F. Dickson, Martha Tillson, J. Matthew Webster, Carl G. Leukefeld

Behavioral Science Faculty Publications

The current study examines protective factors for women who transition from county jails to rural Appalachian communities, areas with limited health and behavioral health services. The study included drug-using women recruited from three jails in rural Appalachia and followed-up at 12-months post-release. Analyses focused on differences between women who remained in the community and those who returned to custody, as well as a multivariate model to determine protective factors for reentry success. At the bivariate level, staying out of jail was associated with being older, having a job, not using drugs, stable housing, receiving health treatment, and having prosocial peers. …

N-Glycosylation-Defective Splice Variants Of Neuropilin-1 Promote Metastasis By Activating Endosomal Signals, Xiuping Huang, Qing Ye, Min Chen, Aimin Li, Wenting Mi, Yuxin Fang, Yekaterina Y. Zaytseva, Kathleen L. O'Connor, Craig W. Vander Kooi, Side Liu, Qing-Bai She

Markey Cancer Center Faculty Publications

Neuropilin-1 (NRP1) is an essential transmembrane receptor with a variety of cellular functions. Here, we identify two human NRP1 splice variants resulting from the skipping of exon 4 and 5, respectively, in colorectal cancer (CRC). Both NRP1 variants exhibit increased endocytosis/recycling activity and decreased levels of degradation, leading to accumulation on endosomes. This increased endocytic trafficking of the two NRP1 variants, upon HGF stimulation, is due to loss of N-glycosylation at the Asn150 or Asn261 site, respectively. Moreover, these NRP1 variants enhance interactions with the Met and β1-integrin receptors, resulting in Met/β1-integrin co-internalization and co-accumulation on endosomes. This provides persistent …

Advances In Gene Ontology Utilization Improve Statistical Power Of Annotation Enrichment, Eugene Waverly Hinderer Iii, Robert M. Flight, Rashmi Dubey, James N. Macleod, Hunter N. B. Moseley

Maxwell H. Gluck Equine Research Center Faculty Publications

Gene-annotation enrichment is a common method for utilizing ontology-based annotations in gene and gene-product centric knowledgebases. Effective utilization of these annotations requires inferring semantic linkages by tracing paths through edges in the ontological graph, referred to as relations. However, some relations are semantically problematic with respect to scope, necessitating their omission or modification lest erroneous term mappings occur. To address these issues, we created the Gene Ontology Categorization Suite, or GOcats—a novel tool that organizes the Gene Ontology into subgraphs representing user-defined concepts, while ensuring that all appropriate relations are congruent with respect to scoping semantics. Here, we demonstrate the …

Imaging Of Glucose Metabolism By 13c-Mri Distinguishes Pancreatic Cancer Subtypes In Mice, Shun Kishimoto, Jeffrey R. Brender, Daniel R. Crooks, Shingo Matsumoto, Tomohiro Seki, Nobu Oshima, Hellmut Merkle, Penghui Lin, Galen Reed, Albert P. Chen, Jan Henrik Ardenkjaer-Larsen, Jeeva Munasinghe, Keita Saito, Kazutoshi Yamamoto, Peter L. Choyke, James Mitchell, Andrew N. Lane, Teresa W. M. Fan, W. Marston Linehan, Murali C. Krishna

Center for Environmental and Systems Biochemistry Faculty Publications

Metabolic differences among and within tumors can be an important determinant in cancer treatment outcome. However, methods for determining these differences non-invasively in vivo is lacking. Using pancreatic ductal adenocarcinoma as a model, we demonstrate that tumor xenografts with a similar genetic background can be distinguished by their differing rates of the metabolism of 13C labeled glucose tracers, which can be imaged without hyperpolarization by using newly developed techniques for noise suppression. Using this method, cancer subtypes that appeared to have similar metabolic profiles based on steady state metabolic measurement can be distinguished from each other. The metabolic maps from …

Rna-Based Compositions And Adjuvants For Prophylactic And Therapeutic Treatment, Peixuan Guo, Hui Li, Emil F. Khisamutdinov, Daniel L. Jasinski

Pharmaceutical Sciences Faculty Patents

The present invention is directed towards an artificial RNA nano structure comprising multiple external strands of RNA, each external strand comprising about 40-50 nucleotides; one internal strand of RNA comprising more than about 50 nucleotides; the internal strands and external strands assembled to form a triangle nanostructure, a square nanostructure, or a polygon nanostructure and a pRNA three-way junction (3WJ) motif at each vertex of the nanostructure. Such nanostructure can be provided in a composition together with an adjuvant for use in inducing the production of high affinity neutralizing antibodies or inhibitory antibodies, inducing the production of cytokines, inducing an …

The Effects Of Aging On Sleep Parameters In A Healthy, Melatonin-Competent Mouse Model, Jiffin K. Paulose, Chanung Wang, Bruce F. O'Hara, Vincent M. Cassone

Biology Faculty Publications

Background: Sleep disturbances are common maladies associated with human age. Sleep duration is decreased, sleep fragmentation is increased, and the timing of sleep onset and sleep offset is earlier. These disturbances have been associated with several neurodegenerative diseases. Mouse models for human sleep disturbances can be powerful due to the accessibility to neuroscientific and genetic approaches, but these are hampered by the fact that most mouse models employed in sleep research have spontaneous mutations in the biosynthetic pathway(s) regulating the rhythmic production of the pineal hormone melatonin, which has been implicated in human sleep.

Purpose and method: The present study …

Innovative Solutions For State Medicaid Programs To Leverage Their Data, Build Their Analytic Capacity, And Create Evidence-Based Policy, Lauren Adams, Susan Kennedy, Lindsay Allen, Andrew Barnes, Tom Bias, Dushka Crane, Paul Lanier, Rachel Mauk, Shamis Mohamoud, Nathan Pauly, Jeffery C. Talbert, Cynthia Woodcock, Kara Zivin, Julie Donohue

Pharmacy Practice and Science Faculty Publications

As states have embraced additional flexibility to change coverage of and payment for Medicaid services, they have also faced heightened expectations for delivering high-value care. Efforts to meet these new expectations have increased the need for rigorous, evidence-based policy, but states may face challenges finding the resources, capacity, and expertise to meet this need. By describing state-university partnerships in more than 20 states, this commentary describes innovative solutions for states that want to leverage their own data, build their analytic capacity, and create evidence-based policy. From an integrated web-based system to improve long-term care to evaluating the impact of permanent …