Medicine and Health Sciences Commons^™

Anxiolytic Intervention: Modulation Of Cell Types Due To Nicotine Withdrawal, Taylor Elder

Theses and Dissertations--Pharmacy

Nicotine use disorder (NUD) remains a leading cause of preventable disease, yet the neurobiological mechanisms underlying nicotine withdrawal are incompletely understood. Emerging evidence implicates neuroimmune signaling and astrocytic regulation of glutamate in shaping the withdrawal-associated affective phenotype. This dissertation investigated these processes using multiple nicotine administration paradigms including osmotic minipump implant, cigarette smoke exposure, and nicotine vapor inhalation to model diverse routes of human nicotine intake.

Chapter 2 examines the effects of these three modes of administration on neuroinflammation and validation of nicotine delivery. Nicotine exposure was confirmed through receptor [³H]Epibatidine nAChR binding assay and serum cotinine measurements. …

Investigating The Role Of Dynamic Signaling Of Nrg3-Erbb4 In The Prefrontal Cortex In Mediating Nicotine Withdrawal Phenotypes, Emily Prantzalos

Theses and Dissertations--Pharmacy

While several pharmacotherapies are currently available for nicotine use disorder (NUD), smoking cessation success rates remain below 10% each year. The molecular mechanisms underlying failed quit attempts continue to represent a critical gap in our knowledge. However, recent advances in understanding the genetic contributions to nicotine dependence offer a promising avenue for developing more effective cessation therapies. Prior research has identified genetic variation in Neuregulin 3 (Nrg3) and its cognate receptor ErbB4 as potential contributors to affective nicotine withdrawal (WD) phenotypes and cessation outcomes. Therefore, this dissertation aims to systematically investigate the region-specific, functional role of the Neuregulin Signaling Pathway …

Leveraging Transcriptomics And Behavior To Investigate Potential Neuronal And Glial Drivers Of Substance Use Disorder Endophenotypes, Jack V. Keady

Theses and Dissertations--Pharmacy

Over 54 million Americans needed substance use treatment in 2023. While there are many facets of substance use disorder, two major issues of interest are the negative reinforcing aspects of substances of abuse, manifesting in part as withdrawal symptomologies, and why a subset of people who use substances of abuse escalate to a use disorder. Nicotine exposure models were used to investigate the mechanisms of withdrawal endophenotypes, as smoking is the leading cause of preventable death in the United States, and a fentanyl self-administration model was used to probe individual differences in escalation phenotypes, as 80% of overdose deaths in …

The Impact Of Maternal Environmental Exposures On The Immune Landscape Of The Maternal-Fetal Interface, Heather E. True

Theses and Dissertations--Pharmacy

Maternal environmental exposures and inflammation are known to impact fetal development in utero as well as increase the risk for chronic diseases later in life. Therefore, it is essential that we understand how the maternal environment alters placental structure and immune function.

Therefore, we isolated fetal (chorionic villous) tissues from the placentas of healthy pregnant participants (control) and those with inflammatory conditions, including SARS-COV-2 infection, pregravid obesity, and opioid use disorder. Isolated placental leukocytes were subjected to a series of assays to uncover the phenotypic, functional, and transcriptional (single-cell RNA-sequencing) landscape of placental immune cells. Additional placental tissues were subjected …

Impact Of Hyperthermia And Mitomycin C On Heat Shock Proteins, Mismatch Repair Proteins, And Cytotoxicity In Colon Cancer, Anna M. Reagan

Theses and Dissertations--Clinical and Translational Science

Cytoreductive surgery and heated intraperitoneal chemotherapy (HIPEC) is a treatment used for primary peritoneal malignancy or metastases, including colon cancer. We aimed to explore the effects of hyperthermia and/or mitomycin C (MMC) on mismatch repair (MMR) proteins and heat shock proteins (hsps) and the potential for post-HIPEC treatment with pembrolizumab treatment. Colon cancer cells were treated with hyperthermia and/or MMC for 90 minutes. Subcellular fractionation and immunofluorescent imaging were performed to identify protein abundance and localization of MSH2, MLH1, hsp70, and hsp27. Proteomics analysis was performed for HT29 cells. HT29 cells and patient-derived organoids (PDOs) underwent simulated HIPEC and treatment …

Early Adversity, Impulsivity, And Health Behaviors, Amy Lynn Meadows

Theses and Dissertations--Clinical and Translational Science

Childhood trauma and early adversity are associated with a variety of negative health outcomes, some of which may be mediated by changes to impulsivity as described by the cumulative risk model. The purpose of this project is to provide insight into the effects of cumulative adverse childhood experience on impulsivity in various populations. Three studies examine the effects of early adversity on impulsivity in normal volunteers, parents caring for a child with medical needs, and in patients with diabetes or pre-diabetes with data collected through crowdsourcing. The strongest effects for early adversity on impulsivity were seen in the patients with …

Enhancing Public Health Surveillance: Development And Validation Of Machine Learning Models For Suspected Opioid Overdose Detection In Emergency Medical Services Data, Peter J. Rock

Theses and Dissertations--Clinical and Translational Science

The ongoing opioid overdose crisis in the United States requires timely and accurate surveillance systems to inform public health responses. Traditional public health surveillance methods rely on hospital discharge data and death certificates, which suffer from significant reporting delays and miss cases where patients refuse hospital transportation. Emergency Medical Services (EMS) data presents a promising alternative with advantages in timeliness and case ascertainment but lacks validated definitions for suspected opioid overdose (SOO).

This dissertation addresses this critical gap through the development, validation, and fairness assessment of machine learning models with natural language processing (ML-NLP) for identifying SOOs in EMS data. …

Exploring Healthcare Access In Telehealth Through Spanish-Speaking Patients’ Perspectives: A Scoping Review, Abigail J. Verst

Theses and Dissertations--Communication Sciences and Disorders

Background: Telehealth offers a potential solution to addressing access barriers experienced by Spanish-speaking patients. This scoping review aimed to explore whether a comprehensive view of healthcare access is being considered when creating telehealth programs for Spanish-speakers. The Conceptual Framework of Access to Healthcare (Levesque et al., 2013) was used to guide access analysis.

Methods: A literature search was conducted across three databases to identify empirical studies in the United States that reported Spanish-speaking patients’ perspectives of telehealth through quantitative questions. Data was collected from the included articles to characterize the type of healthcare providers and telehealth modalities examined in the …

Practicing Clinicians' Views Of The Life Participation Approach To Aphasia Therapy, Stephanie H. Mays

Theses and Dissertations--Communication Sciences and Disorders

The Life Participation Approach to Aphasia therapy (LPAA) aligns with a person-centered, functional approach to speech therapy. Past research has demonstrated that persons with aphasia (PWA) benefit from this approach and prefer it when compared to the traditional medical model to therapy. However, a disconnect between PWA preferences and SLP treatment approaches in therapy persists. This study aims to identify both barriers and facilitators that SLPs face when implementing LPAA. Five CCC-SLPs practicing in the state of KY with experience working with PWA were recruited as participants. Participants were placed into two focus groups, with each group meeting for 2-3 …

M1 Macrophage-Engineered Vesicles Have Anti-Cancer Activity In Ovarian Cancer, Connie Du Cao

Theses and Dissertations--Clinical and Translational Science

Ovarian cancer typically presents at an advanced stage, has a poor prognosis, and is a leading cause of cancer-related deaths in women. Extracellular vesicles (EVs) are cell-derived membrane-bound nanoparticles that function in specific cell-to-cell communication and are under development as novel drug delivery vehicles and modulators of the tumor microenvironment. Artificial cell-derived vesicles (ACDVs) derived from M1 macrophages are able to repolarize M2 macrophages to the M1 phenotype and target tumor cells in in vitro studies.

In this study, we generated engineered EVs (EEVs) by membrane disruption of M1 macrophages (MEVs) in the presence and absence of cisplatin to generate …

Zebrafish Models To Uncover Targetable Mechanisms Of Self-Renewal In T-Cell Acute Lymphoblastic Leukemia, Majd Al-Hamaly

Theses and Dissertations--Pharmacology and Nutritional Sciences

Relapsed T-cell Acute Lymphoblastic Leukemia (T-ALL) patients have dismal prognosis, with 5-year overall survival rates of 10% for adults and 36% for children. Relapse is attributed to the inability of chemotherapy agents to eliminate Leukemia Stem Cells (LSCs) that can repopulate the leukemia. Those cells exist with a unique genetic, transcriptomic, and metabolic profile compared to the rest of the leukemia and thus, finding targeted therapies toward this population of cells can result in disease eradication and elimination of relapse. However, investigating LSCs is challenging-particularly in T-ALL- for two reasons: 1) the lack of robust surface markers that define LSCs …

Cell-Type Specific Apoe4 To Apoe2 ‘Switching’ In Astrocytes And Microglia Alters Alzheimer’S Disease Neuropathology, Lesley R. Golden

Theses and Dissertations--Physiology

Apolipoprotein E (APOE) is the strongest genetic risk factor for late-onset Alzheimer’s disease (LOAD). APOE exists in three common protein isoforms throughout the population: ApoE2 (E2), ApoE3 (E3), and ApoE4 (E4). While APOE allele frequencies and the degree of AD-associated risk vary across different ethnic groups, when compared to the ‘neutral’ and most common E3 allele, the E4 allele confers up to a 33-fold increase in Alzheimer’s Disease (AD) risk. Conversely, the neuroprotective E2 allele decreases AD risk by up to 67%. Here, we aimed to determine the therapeutic potential of cell-type specific APOE allele ‘switching’ and explore …

Biochemical And Biophysical Properties Of Failing Myocardium In Rare Patient Populations, Gregory Nathaniel Milburn

Theses and Dissertations--Physiology

Heart failure has diverse underlying etiologies, complicating research. While some types, like ischemic disease or inherited mutations, are well-studied, research on rarer forms has lagged. Understanding the molecular drivers in these populations may enhance diagnostics and therapies. This work examines two rare groups: patients with ATTR cardiac amyloidosis and those receiving mechanical assist device support. We show that myocardium from patients with amyloidosis has increased fibrosis and reduced force production without changes in cross-bridge kinetics. Additionally, we show that the passive stiffness of amyloidosis myocardium is not different from non-failing myocardium, indicating increased ventricular wall thickness may cause restrictive filling. …

Biochemical Properties Of Cardiac Sarcomeres In Human Heart Failure, Austin Grey Wellette-Hunsucker

Theses and Dissertations--Physiology

Heart failure (HF) exhibits considerable heterogeneity, posing significant challenges for research involving human cohorts. Diastolic dysfunction is a common pathophysiological feature; however, its molecular mechanisms remain incompletely elucidated. Sarcomeric proteins are integral to cardiac contraction and relaxation. Nonetheless, the phosphoproteome and the structural remodeling effects of these proteins on diastolic function within the context of HF have not been comprehensively characterized. This study examined sarcomeric modifications in diastolic dysfunction in human HF, focusing on Dilated and Ischemic HF, with non-failing donor hearts as controls. Analyzing myocardial samples from ~150 patients using electrophoretic and biochemical techniques, it found significant titin remodeling …

Development And Clinical Validation Of Automated Same-Day Stereotactic Treatment Procedures For Multiple Brain Metastases And Recurrent Head And Neck Cancers, Shane Mccarthy

Theses and Dissertations--Radiation Medicine

As technology advances, more and more cancer patients are benefiting from the use of stereotactic radiosurgery and radiotherapy (SRS/SRT) to treat their disease. One such technology, Varian’s HyperArc high-definition radiosurgery module, a tool to help facilitate the treatment of brain metastases on a medical linear accelerator (LINAC), has been demonstrated to achieve comparable low dose spillage and target conformity compared to the current gold standard for intracranial malignancies, the Elekta Gamma Knife. Furthermore, due to HyperArc’s single-isocenter multiple lesion approach, the treatment can be delivered in a significantly shorter amount of time. Unfortunately, the manual process of creating these stereotactic …

Assessing The Effectiveness Of A Modified Cook Together Eat Together Program On Food Resource Management Behaviors In A Rural Setting, Johanna K. Poysti

Theses and Dissertations--Nutrition and Food Systems

This study evaluated the effectiveness of a modified, hybrid Cook Together, Eat Together (CTET) program on food resource management behaviors in a rural setting. A six-week intervention combining virtual and in-person sessions aimed to improve health behaviors, food resource management skills, and self-efficacy. Although most behavioral changes were not statistically significant, participants reported increased confidence in cooking healthy meals on a budget. Positive qualitative feedback from focus group discussions indicated program feasibility and engagement. Strengths and limitations of the study were discussed as well as recommendations for future research were given.

Gene Expression In Relation To Bone Fractures In Throughbred Racehorses, Anna M. Rauber-Ramos

Theses and Dissertations--Veterinary Science

Evidence that fractures in Thoroughbred racehorses are outcomes of chronic bone microdamage has led to extensive research into identifying horses at increased risk of fracture. This includes the use of biomarkers and messenger RNA (mRNA) as a measure of bone turnover. Previous research has found expression differences in horses with fractures compared to controls. Utilizing pre-race whole blood samples collected over an 18-month period from Thoroughbred racehorses in Southern California, RNA-sequencing was conducted on horses with bone fractures and race-matched controls to identify differences in gene expression. Focusing on third metacarpal (MC3) and proximal sesamoid bone (PSB) fractures, differentially expressed …

Engineering Novel Biomimetic Models Of Equine Host-Microbe Interactions, Lynn M. Leedhanachoke

Theses and Dissertations--Veterinary Science

One major limitation to the study of equine disease is the lack of in vitro models that accurately reflect the dynamic physiology of the horse. Thus, there is a pressing need to develop in vitro systems that recapitulate diverse equine tissue and organ microenvironments. To overcome this deficiency, we developed multiple biomimetic equine organoid systems that can be employed for a variety of investigations aimed at resolving outstanding questions in infectious disease pathogenesis, therapeutic development and drug metabolism, host defense mechanisms, immune-modulated disease, and equine developmental biology. Our innovative platform incorporates novel equine intestinal enteroid and airway organoid models derived …

Researching Dementia Indicators Among Rural Populations, Justin S. Yount

Theses and Dissertations--Community & Leadership Development

The study explored potential dementia indicators and risk factors among older adults residing in rural areas who are actively engaged in farming operations. Data was collected in three components a questionnaire, an audiogram test, and a memory impairment screening. 104 people responded to the questionnaire, 133 participants took the audiogram test, and 94 participated in the memory impairment screening. The findings revealed that 80.9% of participants showed no sign of cognitive impairment while 19.1% showed signs of possible impairment. Participants reported moderate levels of physical and social activity, but common risk factors such as elevated BMI, diabetes, hearing loss, and …

Utilitzing A Nurse Triage Model To Decrease The Administrative Burden Of Emr Messaging, Pamela B. Schneider

DNP Projects

Abstract

Background: The volume of Electronic Medical Records (EMR) messages from patients to providers continues to rise, yet clinic workflows have not been adequately restructured to accommodate. Increased EMR, especially the inbasket, is associated with provider burnout and decreased job satisfaction, contributing to provider turnover.

Purpose: To improve the triage and distribution of the EMR messaging workload

Method: A Nurse Triage Flowchart was implemented in the Gastroenterology Clinic at the University of Kentucky to help RNs/MAs triage patient messages for improved workflow. Surveys were completed by RNs/MAs and providers before and three months post-implementation. Data from EPIC over six …

“What We Say Matters”: Reducing Drug Use Stigmatization By Healthcare Professionals Through A Narrative-Based Awareness Campaign, Adam M. Traugott

DNP Projects

Background: Stigma towards substance use has been identified as a contributor to poor care and health outcomes amongst people who use drugs (PWUD), a vulnerable population. Healthcare worker stigma negatively affects the outcomes of individual patients and may have greater public health implications. Methods of addressing drug-use stigma have previously been implemented in a variety of clinical settings. Presenting the lived experience of PWUD to healthcare workers via emotionally compelling narratives has been found to be an effective means of stigma reduction.

Purpose: This study utilized two psychometrically validated tools to measure (1) the baseline prevalence of drug use stigma …

Impact Of Obesity On The Gut Microbiome And Inflammatory Markers During Siv Infection And Antiretroviral Therapy, Casey M. Mcguire, Isaac R. Cinco, Diana Takahashi, Kristin A. Sauter, Melissa Kirigiti, Ilhem Messaoudi, Jonah B. Sacha, Charles T. Roberts, Paul Kievit

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Dysbiosis and impaired gut barrier integrity contribute to chronic immune activation associated with both obesity and HIV infection. Given the increased incidence of obesity in people living with HIV, we explored the impact of obesity on the gut microbiome and microbial translocation (MT) biomarkers during HIV infection and antiretroviral therapy (ART). Lean and obese rhesus macaques were infected with simian immunodeficiency virus (SIV) and subsequently treated with ART. Obese animals exhibited higher initial MT and inflammation biomarkers that remained constant throughout the study, while lean animals exhibited significant increases in these biomarkers that approached levels observed in obese animals. Lean …

Evaluating A Public Health Program Using The Cdc Framework: A Case Study Approach, Brooke A. Poe

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

In Bourbon County, Kentucky, where rural health challenges and chronic disease burdens persist, a coalition of public health partners set out to improve population-level physical activity through an innovative, community-centered initiative. The Bourbon County Physical Activity Program emerged through collaboration between the Bourbon County Health Department, the University of Kentucky College of Public Health, and UK HealthCare. Together, these partners designed a six-month intervention that combined discounted YMCA memberships, partnerships with employers, a physical activity tracking app with behavioral incentives, and community-wide events to promote accessible and sustained engagement.

Guided by the CDC’s framework for program evaluation in public health, …

Influence Of Perceived Health Provider Communication, Diabetes Duration And Age At Diagnosis With Confidence In Diabetes Self-Care, Courtney L. Ortz, Meredith S. Duncan, Oluwatosin Leshi, William B. Burrows, Brittany L. Smalls

Family and Community Medicine Faculty Publications

Introduction: Several factors influence individuals’ confidence to perform diabetes-related self-care activities, including perceived patient-provider communication, diabetes duration and age at diagnosis. It has been well-documented that patient-provider communication is essential when managing chronic diseases such as diabetes; however, the impact of this communication with diabetes duration and age at diabetes diagnosis on confidence in performing self-care behaviors is obscure.

Research design and methods: We utilized data from the 2021 Household Component of the Medical Expenditure Survey among participants 18 years or older who had completed the Diabetes Care Survey. Ordinal logistic regression models were utilized to assess the association between …

Alterations In Whole Muscle Quality And Physiological Cross-Sectional Area Measured With Quantitative Mri Following Acl Injury, Meredith K. Owen, Lauren Richardson, Darren L. Johnson, Moriel H. Vandsburger, Thorsten Feiweier, Katherine L. Thompson, Christopher S. Fry, Peter A. Hardy, Brian W. Noehren

Physical Therapy Faculty Publications

Background: Emerging evidence suggests that there are morphological and physiological changes to the vastus lateralis after an anterior cruciate ligament (ACL) tear. However, it is unclear whether these alterations are limited to just the vastus lateralis or are more representative of widespread changes across the thigh musculature and/or if these changes precede reconstruction. The purpose of this study was to determine T1ρ relaxation time, a measure of extracellular matrix organization in muscle, and physiological cross-sectional area (PCSA) for muscles of the quadriceps and hamstrings of the ACL-deficient and contralateral limbs soon after ACL injury.

Methods: T1ρ and diffusion …

Effects Of An Active Ankle Exoskeleton On The Walking Biomechanics Of Healthy Men, Sridevi Nagaraja, Jose E. Rubio, Junfei Tong, Aravind Sundaramurthy, Anup Pant, Meredith K. Owen, Michael A. Samaan, Brian W. Noehren, Jaques Reifman

Physical Therapy Faculty Publications

Active lower-body exoskeleton devices can decrease the energy requirement of the human body by providing mechanical assistance to lower-body muscles. However, they also alter gait kinematics and kinetics, and it is not well understood whether such alterations are detrimental or beneficial to the human body. In this pilot study, we investigated the impact of walking with an ankle exoskeleton device on the biomechanics of men while carrying a heavy load. We collected computed tomography images and motion-capture data for five young, healthy men who walked 5 km (∼60 min) with a 22.7-kg load, with and without an active ankle exoskeleton …

All-Cause And Exacerbation-Related Readmissions In Thrombotic Microangiopathy Requiring Plasmapheresis: A Population-Based Cohort Study, Alexander R. Thebert, Toru Yoshino, Sae X. Morita, Misa Ito, Ayman Qasrawi, Hirotaka Kato

Internal Medicine Faculty Publications

Objective: Thrombotic microangiopathy (TMA) is a serious condition characterized by microangiopathic hemolytic anemia and thrombocytopenia, with high exacerbation rates. This study examined all-cause and exacerbation-related readmission risks among patients hospitalized with TMA requiring plasmapheresis.

Materials and Methods: Secondary analysis of the 2020 Nationwide Readmission Database was conducted, including discharge data from non-federal hospitals in 31 U.S. states. Patients aged 18 years or older admitted non-electively with a primary or secondary diagnosis of TMA requiring plasmapheresis were included. Exacerbation-related readmission was defined as subsequent admission requiring plasmapheresis within 7 or 30 days after the original discharge. Multivariable logistic regression and Cox …

Clonal Hematopoiesis Of Indeterminate Potential And The Risk Of Cognitive Impairment In The Women’S Health Initiative Memory Study, Yasminka A. Jakubek, Aaron P. Smith, Xiaoyan I. Leng, Megan E. Hall, Daniel Ezzat, Yash Pershad, Jason M. Collins, Md Mesbah Uddin, David W. Fardo, Pradeep Natarajan, Alexander G. Bick, Jacob O. Kitzman, Michael C. Honigberg, Kathleen M. Hayden, Joann E. Manson, Siddhartha Jaiswal, Eric A. Whitsel, Alexander P. Reiner

Internal Medicine Faculty Publications

INTRODUCTION

Clonal hematopoiesis of indeterminate potential (CHIP) confers an increased risk of several chronic aging-related diseases. Paradoxically, CHIP was associated with lower risk of dementia in recent studies.

METHODS

We examined associations between baseline CHIP and incident mild cognitive impairment (MCI) and/or probable dementia in the Women's Health Initiative Memory Study. CHIP was detected using blood-based targeted sequencing. Cox proportional hazards models examined time to onset of cognitive impairment, adjusting for traditional risk factors.

RESULTS

Using a conventional variant allele fraction (VAF) threshold of 2%, CHIP was not associated with incident cognitive impairment. The presence of larger CHIP clone (VAF …

Dual Biologic Therapy Induces Remission In Refractory Crohn’S Disease With Vedolizumab And Ustekinumab, Syed Adeel Hassan, Courtney Perry, Patrick Carey, Durham Colohan, Mohamed Gebril Eltaher, Nabila Dawoud, Mahmoud Elkammar, Waqas Rasheed, Casie Mayne, Amy Stuffelbeam, Deborah R. Auer Flomenhoft, Terrence A. Barrett

Internal Medicine Faculty Publications

Background

Despite advancements in the therapeutic armamentarium for Crohn’s disease (CD), biologic and small molecule monotherapies are associated with sub-optimal response and remission rates. Utilizing dual biologic therapy (DBT) holds the potential to increase efficacy in the treatment of refractory or partially responsive CD. Evidence pertaining to this strategy remains limited. Methods

We retrospectively examined refractory CD patients treated with a combination of ustekinumab and vedolizumab. Outcomes to DBT at week (wk) 52 were compared to monotherapy. The primary outcome constituted corticosteroid-free remission. Secondary outcomes included adverse events, infections, hospitalizations, surgeries, treatment persistence, and disease clearance. Results

Sixteen of 21 …

Intracellular Survival Of Staphylococcus Aureus In Macrophages During Osteomyelitis, William A. Lathram, Christopher D. Radka

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Staphylococcus aureus, traditionally viewed as an extracellular pathogen, is increasingly recognized for its ability to persist intracellularly, particularly within macrophages. This intracellular lifestyle is central to osteomyelitis, a chronic bone infection characterized by persistent inflammation, bone destruction, and impaired repair. Within bone, S. aureus exploits macrophage plasticity by driving a shift from pro-inflammatory, bactericidal M1-like states to anti-inflammatory, tissue-reparative M2-like phenotypes. This polarization suppresses immune clearance and promotes an environment conducive to bacterial survival and dissemination. Additional strategies – including biofilm formation, small colony variants, and inhibition of phagolysosomal killing – further enhance persistence and immune evasion. While these …