Digital Commons Network^™

Contributing Factors To Diabetic Brain Injury And Cognitive Decline, Nirmal Verma, Florin Despa

Pharmacology and Nutritional Sciences Faculty Publications

The link of diabetes with co-occurring disorders in the brain involves complex and multifactorial pathways. Genetically engineered rodents that express familial Alzheimer's disease-associated mutant forms of amyloid precursor protein and presenilin 1 (PSEN1) genes provided invaluable insights into the mechanisms and consequences of amyloid deposition in the brain. Adding diabetes factors (obesity, insulin impairment) to these animal models to predict success in translation to clinic have proven useful at some extent only. Here, we focus on contributing factors to diabetic brain injury with the aim of identifying appropriate animal models that can be used to mechanistically dissect the …

Phenylethynyl-Substituted Benzenes And Heterocycles For The Treatment Of Cancer, David S. Watt, Chunming Liu, Vitaliy M. Sviripa, Wen Zhang, Markos Leggas

Molecular and Cellular Biochemistry Faculty Patents

Halogenated phenylethynyl-substituted heterocycles that possess either an N-alkylamino or N,N-dialkylamino group attached to the heterocycle or halogenated phenylethynyl-substituted benzenes that a nitrogen-containing heterocycle attached to the benzene inhibit the proliferation cancer cells and are useful antineoplastic agents.

Enhancing Timeliness Of Drug Overdose Mortality Surveillance: A Machine Learning Approach, Patrick J. Ward, Peter J. Rock, Svetla Slavova, April M. Young, Terry L. Bunn, Ramakanth Kavuluru

Kentucky Injury Prevention and Research Center Faculty Publications

BACKGROUND: Timely data is key to effective public health responses to epidemics. Drug overdose deaths are identified in surveillance systems through ICD-10 codes present on death certificates. ICD-10 coding takes time, but free-text information is available on death certificates prior to ICD-10 coding. The objective of this study was to develop a machine learning method to classify free-text death certificates as drug overdoses to provide faster drug overdose mortality surveillance.

METHODS: Using 2017–2018 Kentucky death certificate data, free-text fields were tokenized and features were created from these tokens using natural language processing (NLP). Word, bigram, and trigram features were created …

A Genome-Wide Assessment Of The Ancestral Neural Crest Gene Regulatory Network, Dorit Hockman, Vanessa Chong-Morrison, Stephen A. Green, Daria Gavriouchkina, Ivan Candido-Ferreira, Irving T. C. Ling, Ruth M. Williams, Chris T. Amemiya, Jeramiah J. Smith, Marianne E. Bronner, Tatjana Sauka-Spengler

Biology Faculty Publications

The neural crest (NC) is an embryonic cell population that contributes to key vertebrate-specific features including the craniofacial skeleton and peripheral nervous system. Here we examine the transcriptional and epigenomic profiles of NC cells in the sea lamprey, in order to gain insight into the ancestral state of the NC gene regulatory network (GRN). Transcriptome analyses identify clusters of co-regulated genes during NC specification and migration that show high conservation across vertebrates but also identify transcription factors (TFs) and cell-adhesion molecules not previously implicated in NC migration. ATAC-seq analysis uncovers an ensemble of cis-regulatory elements, including enhancers of Tfap2B, …

Development Of A Non-Invasive Device For Swallow Screening In Patients At Risk Of Oropharyngeal Dysphagia: Results From A Prospective Exploratory Study, Catriona M. Steele, Rajat Mukherjee, Juha M. Kortelainen, Harri Pölönen, Michael Jedwab, Susan L. Brady, Kayla Brinkman Theimer, Susan Langmore, Luis F. Riquelme, Nancy B. Swigert, Philip M. Bath, Larry B. Goldstein, Richard L. Hughes, Dana Leifer, Kennedy R. Lees, Atte Meretoja, Natalia Muehlemann

Neurology Faculty Publications

Oropharyngeal dysphagia is prevalent in several at-risk populations, including post-stroke patients, patients in intensive care and the elderly. Dysphagia contributes to longer hospital stays and poor outcomes, including pneumonia. Early identification of dysphagia is recommended as part of the evaluation of at-risk patients, but available bedside screening tools perform inconsistently. In this study, we developed algorithms to detect swallowing impairment using a novel accelerometer-based dysphagia detection system (DDS). A sample of 344 individuals was enrolled across seven sites in the United States. Dual-axis accelerometry signals were collected prospectively with simultaneous videofluoroscopy (VFSS) during swallows of liquid barium stimuli in thin, …

Altering Social Cue Perception Impacts Honey Bee Aggression With Minimal Impacts On Aggression-Related Brain Gene Expression, James W. Harrison, Joseph H. Palmer, Clare C. Rittschof

Entomology Faculty Publications

Gene expression changes resulting from social interactions may give rise to long term behavioral change, or simply reflect the activity of neural circuitry associated with behavioral expression. In honey bees, social cues broadly modulate aggressive behavior and brain gene expression. Previous studies suggest that expression changes are limited to contexts in which social cues give rise to stable, relatively long-term changes in behavior. Here we use a traditional beekeeping approach that inhibits aggression, smoke exposure, to deprive individuals of aggression-inducing olfactory cues and evaluate whether behavioral changes occur in absence of expression variation in a set of four biomarker genes …

Visualization And Quantification Of Post-Stroke Neural Connectivity And Neuroinflammation Using Serial Two-Photon Tomography In The Whole Mouse Brain, Katherine Poinsatte, Dene Betz, Vanessa O. Torres, Apoorva D. Ajay, Shazia Mirza, Uma M. Selvaraj, Erik J. Plautz, Xiangmei Kong, Sankalp Gokhale, Julian P. Meeks, Denise M. O. Ramirez, Mark P. Goldberg, Ann M. Stowe

Neurology Faculty Publications

Whole-brain volumetric microscopy techniques such as serial two-photon tomography (STPT) can provide detailed information on the roles of neuroinflammation and neuroplasticity throughout the whole brain post-stroke. STPT automatically generates high-resolution images of coronal sections of the entire mouse brain that can be readily visualized in three dimensions. We developed a pipeline for whole brain image analysis that includes supervised machine learning (pixel-wise random forest models via the “ilastik” software package) followed by registration to a standardized 3-D atlas of the adult mouse brain (Common Coordinate Framework v3.0; Allen Institute for Brain Science). These procedures allow the detection of cellular fluorescent …

Trouble In The Tails? What We Know About Earnings Nonresponse 30 Years After Lillard, Smith, And Welch, Christopher R. Bollinger, Barry T. Hirsch, Charles M. Hokayem, James P. Ziliak

Economics Faculty Publications

Earnings nonresponse in household surveys is widespread, yet there is limited knowledge of how nonresponse biases earnings measures. We examine the consequences of nonresponse on earnings gaps and inequality using Current Population Survey individual records linked to administrative earnings data. The common assumption that earnings are missing at random is rejected. Nonresponse across the earnings distribution is U-shaped, highest in the left and right tails. Inequality measures differ between household and administrative data due in part to nonresponse. Nonresponse biases earnings differentials by race, gender, and education, particularly in the tails. Flexible copula-based models can account for nonrandom nonresponse.

Hospitalization-Associated Change In Gait Speed And Risk Of Functional Limitations For Older Adults, Wei Duan-Porter, Tien N. Vo, Kristen Ullman, Lisa Langsetmo, Elsa S. Strotmeyer, Brent C. Taylor, Adam J. Santanasto, Peggy M. Cawthon, Anne B. Newman, Eleanor M. Simonsick, Teresa M. Waters, Kristine E. Ensrud

Health Management and Policy Faculty Publications

BACKGROUND: Hospitalization-associated functional decline is a common problem for older adults, but it is unclear how hospitalizations affect physical performance measures such as gait speed. We sought to determine hospitalization-associated change in gait speed and likelihood of new limitations in mobility and activities of daily living (ADLs).

METHODS: We used longitudinal data over 5 years from the Health, Aging and Body Composition Study, a prospective cohort of black and white community-dwelling men and women, aged 70-79 years, who had no limitations in mobility (difficulty walking 1/4 mile or climbing 10 steps) or ADLs (transferring, bathing, dressing, and eating) at baseline. …

Healthy Way: Wellness In All Youth, Melissa Slone, Frances J. Feltner

Center of Excellence in Rural Health Presentations

Healthy WAY encourages student led teams to work collectively on an identified problem, by reviewing local data, trends, and research to develop a strategic plan of action with key stakeholders in their schools and communities.

Community organizations can partner to invest in initiatives like Healthy WAY to restore hope and resilience in our youth. Tips to ensure success include: Organizational support, a staff mentor dedicated to the project for the entire period, partners in the school systems and venues for the students to share their outcomes.

The Value Of Innovation To Implementation Program (Vi2p): A Strategic Approach To Aligning And Leveraging Academic Research And Clinical Care Missions, Jing Li, Mark V. Williams, Cecilia Page, Lisa A. Cassis, Philip A. Kern, Robert S. Dipaola

Clinical and Translational Science Faculty Publications

Problem: Inefficient implementation of evidence-based care garners increasing attention as a source of suboptimal value of clinical care, and integration of quality improvement methodology into clinical practice represents a potential solution. Academic medical centers (AMCs) often have expertise in implementation science, yet it is not leveraged effectively to solve operational inefficiencies or to rapidly implement evidence-based practices (EBPs).

Approach: To leverage in-house research expertise, the University of Kentucky (UK) College of Medicine and Center for Health Services Research (CHSR) launched a pilot awards program—Value of Innovation to Implementation Program (VI2P)—across its health system and six health professional colleges. Criteria for …

Image Anaysis For Predicting Body Weight In Humans, Jeffrey S. Barrett, Chee Ng

Pharmaceutical Sciences Faculty Patents

Systems and methods for determining body weight predictions and human conditions are disclosed. A body weight may be predicted by capturing at least one image of a human, and determining, from the image, a body weight prediction of the human by processing the at least one image with a data processor. The body weight prediction may further be based on an age-based weight factor. A model such as a neural network model may be used to predict body weight.

Usgs 104(B) Grant Program: Kentucky’S Fy 2018 Projects, Emily Koyagi, Steve Evans, Lindell Ormsbee

KWRRI Annual Technical Reports (USGS’s 104b Grant Program)

The Kentucky Water Resources Research Institute (KWRRI) is one of 54 federally authorized water resource institutes or centers throughout the United States and its territories. It operates under the authority of the Water Resources Research Act of 1964 (P.L. 88-379 codified at 42 U.S.C. 10301 et seq.) through the Water Resources Research Institutes Program administered by the United States Geological Survey (USGS). KWRRI’s annual base grant program under section 104(b) supports the following objectives specified in the Water Resources Research Act:

1. Plan, conduct, or otherwise arrange for competent applied and peer reviewed research that fosters: a. improvements in water …

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 …

Socioemotional Selectivity And Psychological Health In Amyotrophic Lateral Sclerosis Patients And Caregivers: A Longitudinal, Dyadic Analysis, Suzanne C. Segerstrom, Edward J. Kasarskis, David W. Fardo, Philip M. Westgate

Psychology Faculty Publications

Objective: Socioemotional selectivity theory predicts that as the end of life approaches, goals and resources that provide immediate, hedonic reward become more important than those that provide delayed rewards. This study tested whether these goal domains differentially affected psychological health in the context of marital dyads in which one partner had been diagnosed with amyotrophic lateral sclerosis (ALS), a life-limiting disease.

Design: ALS patients (N = 102) being treated in three multidisciplinary clinics and their spouses (N = 100) reported their loneliness, financial worry and psychological health every 3 months for up to 18 months.

Main …

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.

.

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 …

Connective Tissue Fibroblasts From Highly Regenerative Mammals Are Refractory To Ros-Induced Cellular Senescence, Sandeep Saxena, Hemendra J. Vekaria, Patrick G. Sullivan, Ashley W. Seifert

Biology Faculty Publications

A surveillance system in mammals constantly monitors cell activity to protect against aberrant proliferation in response to damage, injury and oncogenic stress. Here we isolate and culture connective tissue fibroblasts from highly regenerative mammals (Acomys and Oryctolagus) to determine how these cells interpret signals that normally induce cellular senescence in non-regenerating mammals (Mus and Rattus). While H₂O₂ exposure substantially decreases cell proliferation and increases p53, p21, p16, and p19 in cells from mice and rats, cells from spiny mice and rabbits are highly resistant to H₂O₂. Quantifying oxygen consumption …

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 …

Fgf-Signaling Is Compartmentalized Within The Mesenchyme And Controls Proliferation During Salamander Limb Development, Sruthi Purushothaman, Ahmed Elewa, Ashley W. Seifert

Biology Faculty Publications

Although decades of studies have produced a generalized model for tetrapod limb development, urodeles deviate from anurans and amniotes in at least two key respects: their limbs exhibit preaxial skeletal differentiation and do not develop an apical ectodermal ridge (AER). Here, we investigated how Sonic hedgehog (Shh) and Fibroblast growth factor (Fgf) signaling regulate limb development in the axolotl. We found that Shh-expressing cells contributed to the most posterior digit, and that inhibiting Shh-signaling inhibited Fgf8 expression, anteroposterior patterning, and distal cell proliferation. In addition to lack of a morphological AER, we found that salamander …