Best3-Mediated Mekk2/3 Activation: A Novel Therapeutic Target In Aortopathies, Tatiana Zyrianova, Benjamin Lopez, Kathlyn Zou, Charles Gu, Dayna Pham, Sriharsha Talapaneni, Christopher M. Waters, Riccardo Olcese, Andreas Schwingshackl

Saha Cardiovascular Research Center Faculty Publications

Influenza-A virus (IAV) infects yearly an estimated one billion people worldwide, resulting in 300,000–650,000 deaths. Preventive vaccination programs and antiviral medications represent the mainstay of therapy, but with unacceptably high morbidity and mortality rates, new targeted therapeutic approaches are urgently needed. Since inflammatory processes are commonly associated with measurable changes in the cell membrane potential (Em), we investigated whether Em hyperpolarization via TREK-1 (K2P 2.1) K þ channel activation can protect against influenza-A virus (IAV)-induced pneumonia. We infected mice with IAV, which after 5 days caused 10–15% weight loss and a decrease in spontaneous activity, representing a clinically relevant infection. …

Deep Learning, 3d Ultrastructural Analysis Reveals Quantitative Differences In Platelet And Organelle Packing In Covid-19/Sarscov2 Patient-Derived Platelets, Sagar S. Matharu, Cassidy S. Nordmann, Kurtis R. Ottman, Rahul Akkem, Douglas Palumbo, Denzel R. D. Cruz, Kenneth Campbell, Gail Sievert, Jamie L. Sturgill, James Zachary Porterfield, Smita Joshi, Hammodah Rawhi Hammodah Alfar, Chi Peng, Irina D. Pokrovskaya, Jeffrey A. Kamykowski, Jeremy P. Wood, Beth A. Garvy, Maria A. Aronova, Sidney W. Whiteheart, Richard D. Leapman, Brian Storrie

Saha Cardiovascular Research Center Faculty Publications

Platelets contribute to COVID-19 clinical manifestations, of which microclotting in the pulmonary vasculature has been a prominent symptom. To investigate the potential diagnostic contributions of overall platelet morphology and their α-granules and mitochondria to the understanding of platelet hyperactivation and micro-clotting, we undertook a 3D ultrastructural approach. Because differences might be small, we used the high-contrast, high-resolution technique of focused ion beam scanning EM (FIB-SEM) and employed deep learning computational methods to evaluate nearly 600 individual platelets and 30 000 included organelles within three healthy controls and three severely ill COVID-19 patients. Statistical analysis reveals that the α-granule/ mitochondrion-to-plateletvolume ratio …

Lrp1 Protects Against Excessive Superior Mesenteric Artery Remodeling By Modulating Angiotensin Ii–Mediated Signaling, Jackie M. Zhang, Dianaly T. Au, Hisashi Sawada, Michael K. Franklin, Jessica J. Moorleghen, Deborah A. Howatt, Pengjun Wang, Brittany O. Aicher, Brian Hampton, Mary Migliorini, Fenge Ni, Adam E. Mullick, Mashhood M. Wani, Areck A. Ucuzian, Hong S. Lu, Selen C. Muratoglu, Alan Daugherty, Dudley K. Strickland

Saha Cardiovascular Research Center Faculty Publications

Vascular smooth muscle cells (vSMCs) exert a critical role in sensing and maintaining vascular integrity. These cells abundantly express the low-density lipoprotein receptor–related protein 1 (LRP1), a large endocytic signaling receptor that recognizes numerous ligands, including apolipoprotein E–rich lipoproteins, proteases, and protease-inhibitor complexes. We observed the spontaneous formation of aneurysms in the superior mesenteric artery (SMA) of both male and female mice in which LRP1 was genetically deleted in vSMCs (smLRP1–/– mice). Quantitative proteomics revealed elevated abundance of several proteins in smLRP1–/– mice that are known to be induced by angiotensin II–mediated (AngII-mediated) signaling, suggesting that this pathway was dysregulated. …

Macrophage Angiotensin-Converting Enzyme Reduces Atherosclerosis By Increasing Peroxisome Proliferator-Activated Receptor Α And Fundamentally Changing Lipid Metabolism, Duoyao Cao, Zakir Khan, Xiaomo Li, Suguru Saito, Ellen A. Bernstein, Aaron R. Victor, Faizan Ahmed, Aoi O. Hoshi, Luciana C. Veiras, Tomohiro Shibata, Mingtian Che, Lei Cai, Michifumi Yamashita, Ryan E. Temel, Jorge F. Giani, Daniel J. Luthringer, Ajit S. Divakaruni, Derick Okwan-Duodu, Kenneth E. Bernstein

Saha Cardiovascular Research Center Faculty Publications

Aims The metabolic failure of macrophages to adequately process lipid is central to the aetiology of atherosclerosis. Here, we examine the role of macrophage angiotensin-converting enzyme (ACE) in a mouse model of PCSK9-induced atherosclerosis.

Methods and results Atherosclerosis in mice was induced with AAV-PCSK9 and a high-fat diet. Animals with increased macrophage ACE (ACE 10/10 mice) have a marked reduction in atherosclerosis vs. WT mice. Macrophages from both the aorta and peritoneum of ACE 10/10 express increased PPARα and have a profoundly altered phenotype to process lipids characterized by higher levels of the surface scavenger receptor CD36, increased uptake of …

Investigating Visinin-Like Protein 1 And Ubiquitinated Visinin-Like Protein 1 As Mild Traumatic Brain Injury Biomarkers, Yueming Wu

Theses and Dissertations--Chemistry

Traumatic brain injury (TBI) continues to be a significant cause of morbidity and mortality worldwide. Despite significant progress in understanding the complex pathophysiology of TBI, the underlying mechanisms remain poorly understood. The primary brain damage is acute and irreversible. However, secondary brain injuries often develop gradually over months to years, creating an opportunity for critical therapeutic interventions. In the past decade, research on TBI biomarkers has seen significant progress. This progress has been driven by the diverse nature of TBI pathologies and the challenges they present for evaluation, management, and prognosis. TBI biomarker proteins resulting from axonal, neuronal, or glial …

Alzheimer’S Disease Genetics And Short-Chain Fatty Acid Treatment In Studies Of The Murine Gut Microbiome, Diana Zajac

Theses and Dissertations--Physiology

Elucidating the relationship of the gut microbiome in Alzheimer's Disease (AD) risk and pathogenesis is an area of intense interest. Since 60 to 80% of AD risk is related to genetics and APOE alleles represent the most impactful genetic risk factors for AD, their mechanism(s) of action are under intense scrutiny.

First, I conducted a study on APOE targeted replacement mice to investigate the impact of APOE alleles on the murine gut microbiome. The relative abundance of bacteria from the family Ruminococacceae and related genera increased with APOE2 status. The relative abundance of the class Erysipelotrichia increased with APOE4 status, …

The Supine Moving Apprehension Test—Reliability And Validity Among Healthy Individuals And Patients With Anterior Shoulder Instability, Alon Rabin, Ofir Chechik, Margie K. Olds, Timothy L. Uhl, Efi Kazum, Adin Deutsch, Eran Citron, Tal Cohen, Oleg Dolkart, Assaf Bibas, Eran Maman

Physical Therapy Faculty Publications

Background: Performance-based tests for patients with anterior shoulder dislocation are lacking. This study determined the reliability and validity of the supine moving apprehension test designed to assess the ability to control anterior instability loads. Methods: Thirty-six participants were recruited (18 healthy individuals, and 18 patients following anterior shoulder dislocation). Healthy participants performed the supine moving apprehension test on 2 separate occasions to determine test-retest reliability. Patients completed the supine moving apprehension test and the Western Ontario Shoulder Instability index before and 6 months after surgical stabilization of their shoulder. The presence of anterior apprehension was also documented post-operatively. Results: The …

Interactive Association Of Posttraumatic Stress Disorder, Apolipoprotein Ε4 Genotype, And Age On Cognitive Functioning, Karen A. Lawrence, Colton Rippey, Bianca Welikson, Robert H. Pietrzak, Thomas G. Adams Jr.

Psychology Faculty Publications

Background: The ε4 allele of the apolipoprotein (APOE) gene and posttraumatic stress disorder (PTSD) are associated with cognitive deficits. Both associations may vary depending on age. No previous study has examined a possible three‐way interaction between APOE ε4, PTSD, and age on cognitive functioning.

Methods: Data were analyzed from 1244 European‐American U.S. military veterans who participated in the 2011 National Health and Resilience in Veterans Study (NHRVS). Analyses of covariance were used to examine the main effects and in- teractions of APOE ε4, PTSD, and age on learning/working memory (LWM) and attention/psychomotor (APM) performance.

Results: A significant three‐way interaction between …

Cumulative Risk For Children’S Behavior Problems And Child Abuse Potential Among Mothers Receiving Substance Use Treatment: The Unique Role Of Parenting Stress, Stephanie Gusler, Angela Moreland

Psychiatry Faculty Publications

There is a high prevalence of children whose parents suffer with a substance use disorder (SUD), which is associated with negative outcomes for children such as behavior problems and parents’ child abuse potential. To understand negative consequences for children, it is important to consider a cumulative risk model, examining the impact of multiple co-occurring risks, as well as examine unique singular risk factors, such as parenting stress, which may have a direct effect on outcomes as well as mediate an association between cumulative risk and outcomes. Data came from 99 mothers with SUD, engaged in a substance treatment program. Results …

Cannabidiol And Delta-9-Tetrahydrocannabinol Interactions In Male And Female Rats With Persistent Inflammatory Pain, Stevie C. Britch, Rebecca M. Craft

Behavioral Science Faculty Publications

Cannabidiol (CBD) and delta-9-tetrahydrocannabinol (THC), 2 of the primary constituents of cannabis, are used by some individuals to self-treat chronic pain. It is unclear whether the painrelieving effects of CBD alone and in combination with THC are consistent across genders and among types of pain. The present study compared the effects of CBD and THC given alone and in combination in male and female rats with Complete Freund’s adjuvant-induced inflammatory pain. After induction of hindpaw inflammation, vehicle, CBD (0.05−2.5 mg/kg), THC (0.05−2.0 mg/kg), or a CBD: THC combination (3:1, 1:1, or 1:3 dose ratio) was administered i.p. twice daily for …

The Endowment Effect And Temporal Discounting Of Drug And Non-Drug Commodities, Sean D. Regnier, Mark J. Rzeszutek, Justin C. Strickland, Thomas Shellenberg, William W. Stoops

Behavioral Science Faculty Publications

Objectives: Despite a rich history of behavioral economic research on substance use there remains a need for further exploration of behavioral mechanisms that may underlie the etiology or persistence of substance use disorder. The purpose of this study was to measure the association between delay discounting and the endowment effect in people who smoke cigarettes, use cocaine, and controls, using online crowdsourcing. Methods: Participants were categorized to a cocaine group (n = 36), cigarette group (n = 48), or control group (n = 47) based on recent reported drug use. Based on group, participants completed up to three delay discounting …

The Moderating Effect Of Physical Activity On The Relationship Between Bullying And Mental Health Among Sexual And Gender Minority Youth, Sally J. Kirklewski, Ryan J. Watson, Carolyn Lauckner

Behavioral Science Faculty Publications

Background: Sexual and gender minority youth frequently experience bullying, which often contributes to higher depressive symptoms and lower self-esteem. Given that physical activity (PA) can mitigate depressive symptoms and improve self-esteem, we examined the moderating effect of PA on the relationship between bullying and mental health among sexual and gender minority youth.

Methods: Data from the Lesbian, Gay, Bisexual, Transgender, and Queer National Teen Survey (n = 9890) were analyzed. Hierarchical regression analyses examined the influence of history and frequency of being bullied, PA, and the interaction of these variables on depressive symptoms and self-esteem. Simple slopes analyses were used …

Examining Engagement With And Acceptability And Usability Of Real Parenting: A Brief Online Parent-Based Intervention To Reduce Alcohol Use And Consequences Among High School Students, Shannon D. Glenn, Robert Turrisi, Michael L. Hecht, Michael A. Russell, Anne E. Ray

Health, Behavior & Society Faculty Publications

This study is a formative assessment of REAL Parenting (RP): a brief, digital intervention for parents of high school students that encourages parent-teen communication about alcohol and, in turn, aims to prevent teen alcohol use. The aims of this study were to describe engagement with, and acceptability and usability of RP; and to explore the relationship of these measures with each other and with short-term outcomes. Participants were 160 parents randomly assigned to the treatment group who received RP as part of a randomized pilot trial (Mage = 45.43[SD = 7.26], 59.3% female, 56% White, 19% Hispanic). App-based program analytics …

A Mini Review Of What Matters In The Management Of Nas, Is Esc The Best Care?, Enrique Gomez Pomar

Pediatrics Faculty Publications

As the use of opioids and polysubstance by pregnant women has increased over the years, there has also been a sharp increase in cases of neonatal abstinence syndrome (NAS). Classically, infants affected by NAS have been cared for in neonatal intensive care units resulting in an increase of healthcare expenditure and resource utilization as well as separation from the families. Consequently, the Eat, Sleep, and Console (ESC) tool was developed and promoted as a novel method that focuses on maternal/infant dyad during hospital stay while decreasing the use of pharmacological interventions and therefore decreasing the length of stay and healthcare …

Beyond Gatekeeping: Building A Community For Suicide Survivors, Rebecca Thomas

DSW Capstone Projects

Suicide is a complex phenomenon, yet past attempts to change it have relied on an oversimplification that to prevent suicide, suicidal people need professional mental health treatment. Fortunately, that notion has faded. Suicide is now recognized as a public health issue; One that spans various continuums of culture, socioeconomic status, and demographics. With a better understanding and increased recognition of suicide as a public health issue, more stakeholders have engaged in suicide prevention efforts, new research has emerged, and more attention and resources are being dedicated than ever before. This capstone project explores the impact a suicide death has on …

Implementing A Mobile Saliva Rinse Screening For P16 Markers For Hpv (Human Papillomavirus) Positive Head And Neck Cancers In Central Kentucky, Madeline Brown

Theses and Dissertations--Public Health (M.P.H. & Dr.P.H.)

Rates of HPV-related head and neck cancers are increasing across the nation and more specifically, there has been a significant increase in the state of Kentucky. This study focuses on the implementation of a mobile clinic saliva-rinse screening program. This program will be set up at UK Athletics Men's basketball and football games in hopes of recruiting middle aged men ages 45-60, who are the target audience of the study. This is the population with highest prevalence for HPV positive head and neck cancers and also the population least likely to visit their health providers regularly. A quick saliva rinse …

Characterizing Region Iv State Health Agency - Central Office's Workforce Needs: Results From The 2021 Public Health Workforce Interest And Needs Survey (Ph Wins), Ashley Carroll

Theses and Dissertations--Public Health (M.P.H. & Dr.P.H.)

The purpose of this project was to examine the Region IV State Health Agency – Central Office workforce in regards to retention and reasons for leaving; workforce satisfaction levels and how that influences retention; and training gaps among non-supervisors. An extensive review of existing literature was completed and showed that since the great recession, there has been a loss of 40,000 positions at state and local governmental health agencies (Castrucci & Lupi, 2020). In addition, from 2008 to 2019, there has been a 16 percent decline in the national public health workforce, and 47 percent of public health workers plan …

A Case Study In Program Evaluation: Evaluation Of A Hypertension Self Management Program, Bailey N. Schenk

Theses and Dissertations--Public Health (M.P.H. & Dr.P.H.)

The CDC's program evaluation process framework is a six-step approach that guides public health practitioners in the evaluation of public health programs. The framework includes engaging stakeholders, describing the program, focusing the evaluation design, gathering credible evidence, justifying conclusions, and ensuring use and sharing of lessons learned. Each step is important in developing a comprehensive and effective program evaluation. This evaluation discusses the application of the six steps of the CDC's program evaluation process framework and how it was utilized in evaluating a hypertension self-management program at a local health department.

Changes In Severity Of Diabetes At Diagnosis Following The Onset Of The Sars-Cov-2 Pandemic, Annelise King

Theses and Dissertations--Public Health (M.P.H. & Dr.P.H.)

During the SARS-CoV-2 pandemic it was seen that diabetes was a risk factor for severe COVID-19. The objective of this study is to assess the severity of diabetes at diagnosis during the COVID-19 pandemic compared to pre-pandemic to see how the pandemic and SARS-CoV-2 infection impacted the severity of diabetes. This study used University of Kentucky electronic health records of 13,794 patients who developed diabetes. The majority of patients were female, white non-Hispanic, 65+, and living in an urban area. There were differences seen between the COVID-19 positive and negative cohorts in the DKA and HbA₁c variables, with …

Effect Of Medicaid Expansion On Inflammatory Bowel Disease And Healthcare Utilization, Brittany Levy

Theses and Dissertations--Public Health (M.P.H. & Dr.P.H.)

Inflammatory bowel disease (IBD) affects over 3 million adults in America, relaying a

need for chronic disease management. Along with 24 other states, Kentucky expanded the

Medicaid program January 1, 2014. We hypothesize, Medicaid expansion adoption results in

reduced emergency healthcare services, and increased elective healthcare services with a

reduction in overall healthcare utilization by individuals in the adult IBD population.

The Hospital Inpatient Discharge and Outpatient Services Database identify encounters

related to ulcerative colitis or Crohn’s disease from 2009-2020, in Kentucky. Patient

demographics, admission type, discharge, length of stay, and hospital charges were compared.

3386 pre-expansion and 24255 post …

Health Management And Policy Capstone: A Case Study In Program Evaluation, Kelsey R. Gatton

Theses and Dissertations--Public Health (M.P.H. & Dr.P.H.)

Program evaluation of a hypothetical comprehensive hypertension self-management program as directed by the CDC Framework for Program Evaluation in Public Health.

Evaluation Of Facebook Social Media Messages Following The 2022 Eastern Kentucky Floods, Delaney Bonds

Theses and Dissertations--Public Health (M.P.H. & Dr.P.H.)

Purpose: The goal of this study is to examine the availability of disaster-related information online from local health departments in flood-impacted counties in the month following 2022 Eastern Kentucky Floods. This study aims to evaluate Facebook messages by (1) when messages were posted (2) types of posts (3) message content.

Methods: This mix-methods environmental scan of Facebook messages posted by 8 flood-impacted Eastern Kentucky local health departments from July 26^th, 2022, to August 26^th, 2022. Messages were coded for absence or presence of a message feature. These message features were examined to identify features relevant to …

The Prepare Mobile Program For Hiv Prevention In Washington D.C., Gabrielle Cochran

Theses and Dissertations--Public Health (M.P.H. & Dr.P.H.)

Incidence rates of HIV have decreased in the United States in the past decade, but the southern United States has higher rates of HIV than other regions, and cities in the south, like Washington D.C., have some of the highest rates of HIV incidence in the nation. Risky sexual behavior, needle sharing, and substance use increase the risk of transmitting or acquiring HIV, and these behaviors are more common among unhoused people (CDC, 2021; CPPH, 2022).

Expansion of community resources in cities with high levels of HIV have allowed for many people at high risk for HIV to comply with …

Retrospective Analysis Of Non-Ketotic Hyperglycinemia Patients In Central And Eastern Kentucky, Shane Reeves

Theses and Dissertations--Public Health (M.P.H. & Dr.P.H.)

Aim: To obtain a better understanding of the non-ketotic hyperglycinemia (NKH) patient population in regards to clinical features, mortality, geographic clustering, genetics, and incidence rate within the University of Kentucky (UK) catchment area of Central and Eastern Kentucky.

Methods: Patients with ICD codes corresponding to NKH who were treated at UK between January 1, 2008, and July 1, 2022, and who had clinical documentation available for review were identified through UK’s medical records (N=15). Demographic and clinical data were obtained through review of these patient’s charts in the electronic medical record. Differences in features among patients was assessed utilizing Fisher …

Trends In Respirable Coal Mine Dust Concentration (Mg/M3) Based On Coal Miners’ Occupational Designation: An Analysis Of The Msha Coal Dust Samples Data Set (2000-2022), Aaron Blake Charles

Theses and Dissertations--Public Health (M.P.H. & Dr.P.H.)

Rates of Coal Workers' Pneumoconiosis (CWP) have recently increased in prevalence over the past 20 years. Recent regulation (Phase III) by the Mining Safety and Health Administration to lower the coal dust standard to 1.5 mg/m3 has been mandated to assist in reducing the burden of CWP. Occupations in the coal mining industry have different exposures to coal dust depending on their occupational responsibilities. This study examined the respirable coal dust trends for underground and surface mining occupations from 2000 to 2022. The ultimate goal is to see how respirable coal dust exposures have changed in multiple occupations over this …

Health Management And Policy Capstone: A Case Study In Program Evaluation, Bradford Brewer

Theses and Dissertations--Public Health (M.P.H. & Dr.P.H.)

Hypertension has risen steadily among adults in United States over the past 30 years. This increase has also been marked by a significant increase in reported prevalence rates of cardiovascular diseases. In response, the Centers for Disease Control and Prevention (CDC) funded the Lexington-Fayette County Health Department to deliver a hypertension self-management program for adults aged 35 and older. This manuscript follows the six steps of CDC program evaluation to aid Lexington citizens with uncontrolled high blood pressure (≥140/90 mmHg) in successful hypertension self-management. This evidence-based community intervention helps patients take responsibility for managing their hypertension with assistance from health …

Rapid Scoping Review Of The Epidemiological Evidence For Mercury Exposure And Prevalence Of Alzheimer’S Disease, Rebecca Mattingly

Theses and Dissertations--Public Health (M.P.H. & Dr.P.H.)

This rapid scoping review examines the current body of epidemiologic research evaluating the potential linkage between environmental exposure to mercury and Alzheimer's disease (AD). Alzheimer’s disease accounts for 60-80% of all neurodegenerative disease in the United States and was the seventh leading cause of death in Kentucky in 2020. The exact etiology of AD needs further investigation; however, environmental factors such as pesticides, arsenic, cadmium, lead, and mercury have been correlated with development of AD lesions, cognitive decline, and AD. Mercury is a toxic metal that can be found in air, water, and soil, both from natural and human-made sources. …

Blue Oval Sk Battery Park Environmental Impact And Community Guide, Warren Rummage

Theses and Dissertations--Public Health (M.P.H. & Dr.P.H.)

This Capstone Project Paper will discuss the potential effects of the BlueOval SK Battery Park being constructed in Glendale, Kentucky based on knowledge attained from open records requests and available publicly online. Based on the process of attaining said information, a Community Guide has been generated and is available to distribute to concerned community members. It is the hope that this work will enable those in Hardin County, and possibly beyond, to ensure their environment and community health are prioritized during the construction phase and eventual operation of the EV-battery manufacturing faciliities on this massive 1,500 acre plot of land.

Pfas Clinical Guidance, John Bingham

Theses and Dissertations--Public Health (M.P.H. & Dr.P.H.)

Introduction

A broad category of synthetic organic compounds, per- and polyfluorinated alkyl substances (PFAS), forms the impetus for this project. Known compounds in this category are numerous and diverse, with over 4700 identified molecular entities (Panieri, Baralic, Djukic-Cosic, Buha Djordjevic, & Saso, 2022). Their only commonality is the presence of at least one carbon atom that is saturated with fluoride groups. These chemical bonds are exceptionally difficult to break (Tansel, 2022), which incepts both the utility of PFAS compounds and the concerns they raise for human health (Cousins et al., 2020). While PFAS are …

The Relationship Between Maternal Depressive Symptoms And Unsafe Infant Sleep Practices In A Low-Resource Community, Rebecca D. Day, Ketrell L. Mcwhorter, Hartley C. Feld, Steven R. Bronwing

Theses and Dissertations--Public Health (M.P.H. & Dr.P.H.)

Objectives: To determine the relationship between maternal depressive symptoms and unsafe infant sleep intention and practices during and after pregnancy.

Methods: This study recruited 100 women from a small clinic in a low-resource community of Santo Domingo, Ecuador from 2018 to 2020. Information on intention to practice safe sleep was collected during the third trimester of pregnancy and safe sleep practices were assessed at 1 month and 6 months postpartum via survey. Depressive symptoms were measured using the Patient Health Questionnaire 2 (PHQ-2). Using log-binomial regression, we estimated prevalence ratios (PR) and 95% confidence intervals (CI) cross-sectionally at …