Medicine and Health Sciences Commons^™

Magnetic Heating Efficiency Of Magnetite Nanoparticles: Dependence On Size And Alternating Magnetic Field, Sarah E. Kubican

Theses and Dissertations--Biomedical Engineering

Magnetic heating mediated by magnetic iron oxide nanoparticles (MION) has several clinical applications including cancer thermal therapy, tissue thawing for organ preservation, and magnetogenetics. However, current models of magnetic heating, including the widely used linear response theory, inadequately predict MION heating efficiency. An experimental study covering alternating magnetic field (AMF) strengths and frequencies ranging from 3.98 – 27.85 kA/m and 103.6 – 984.1 kHz, respectively, with a range of MION core diameters 9.5- 30.3 nm was conducted to elucidate the relationships between these AMF parameters and MION sizes and the resulting heating efficiencies. Heating efficiency was found to increase approximately …

Pathogen Surveillance Of Viruses And Antimicrobial Resistance Through Wastewater Based Epidemiology, William Strike

Theses and Dissertations--Biomedical Engineering

Pandemic surveillance is a cornerstone in public health safety, as it enables identification of pathogens circulating within a community before they become widespread outbreaks. Wastewater based epidemiology has blossomed in recent years due to its success in the SARS-CoV-2 pandemic, but this form of public health surveillance has a global equity problem. A large majority of the wastewater-based surveillance work has been done in large metropolitan cities with access to advanced testing infrastructure, which poses a challenge as we consider where pandemics have historically emerged. Therefore, there is a need to identify, adapt, and develop workflows to meet the needs …

Targeting Prmt5 In Inflammation And Cancer: A Nexus Of Endotoxin Signaling, Antigen Presentation And Immune Evasion., Jimmy James Msemo

Theses and Dissertations--Medical Sciences

Protein Arginine Methyltransferase 5 (PRMT5) is a member of PRMT family that controls both intrinsic and extrinsic oncogenic processes [1]. Protein arginine methyltransferase 5 (PRMT5) is a type II methyltransferase that exerts widespread influence over gene expression, splicing, DNA repair, and immune regulation through symmetric dimethylation of arginine residues on histone and non-histone proteins [2]. The addition of methyl groups induces gene silencing through producing dictatorial histone marks like H2AR3ne2s, H3R8me2s and H4R3mes [3], which act as epigenetic repressive marks on gene promoters. In non-histone proteins, PRMT5 can methylate and regulate transcription factor proteins such as p53, E2F1, and p65, …

Investigating Regulation And The Regulome Of The Nucleic Acid Binding Protein Spovg Within Borrelia Burgdorferi, Timothy C. Saylor

Theses and Dissertations--Medical Sciences

Prior studies indicated Borrelia burgdorferi SpoVG protein was regulated, SpoVG binds specifically to a number of nucleic acids, and SpoVG binds to the non-variable section of the major virulence factor vlsE. Although a direct transcriptional activator or inhibitor was not elucidated, it is shown that SpoVG is regulated based on cell culture density independent of the growth rate of B. burgdorferi, indicating that SpoVG regulation is outside the scope of the alternative sigma factor RpoS. Using a dCas9 CRISPRi construct to target SpoVG resulted in protein expression trending towards upregulation of the BosR-RpoS regulon, and a marked decrease …

Cellular And Behavioral Consequences Of Psychedelic Drug Action In The Claustrum, Tanner L. Anderson

Theses and Dissertations--Neuroscience

Psychedelics are rapidly garnering research attention for their ability to successfully treat a variety of psychiatric diseases after one or a handful of treatments in recent clinical research. Among the conditions treated is substance use disorder (SUD), which afflicted 48.5 million (16.7%) Americans aged 12 and older in 2023 (NSDUH). As clinical trial results continue to show lasting positive effects of psychedelic psychotherapy, there remains an enormous gap in knowledge regarding how these drugs cause lasting changes in the brain to achieve these therapeutic effects. It has been suggested that psychedelics must induce rapid and long-lasting neuronal plasticity in order …

Leveraging Clinical Standards To Improve The Translational Relevance Of Therapies For Experimental Spinal Cord Injury, Aaron L. Silverstein

Theses and Dissertations--Neuroscience

Efforts to improve treatment of spinal cord injury (SCI) often use animals to develop effective therapeutics, intending to improve the survival and the quality of life of persons with SCI. Over half of all SCIs in the United States occur at the cervical level and often cause locomotor deficits and life-threatening breathing dysfunction. Thus, my dissertation is focused on this important patient population.

After beginning with a description of translational research and surveying SCI from a clinical standpoint, I turned to describe experimental models of cervical SCI and more detailed neuroimmunological findings relevant to my work. Then, I conducted a …

Immune Dynamics And B Cell Contributions To Neuroplasticity And Recovery After Stroke, Thomas A. Ujas

Theses and Dissertations--Neuroscience

This dissertation explores the dynamic interplay between the immune system and the brain across stroke and aging using clinical, post-mortem, and pre-clinical models. The immune system plays critical roles in shaping brain function, responding to injury, and mediating recovery. These studies aim to enhance our understanding of neuroimmune dynamics across spatial and temporal dimensions.

In the first part, we conducted longitudinal sampling of aneurysmal subarachnoid hemorrhage (aSAH) patients to track immune cell and cytokine changes at days 3, 5, 7, 10, and 14 post-stroke, with a focus on delayed cerebral ischemia (DCI), a common complication. We observed distinct temporal patterns, …

Understanding The Impact Of The Medicaid Expansion On Hospital Length Of Stay And Emergency Department Use In Kentucky, Cameron Bushling

Theses and Dissertations--Epidemiology and Biostatistics

Three related analyses were performed to try to understand the immediate effects of Medicaid expansion on hospital systems in Kentucky. Medicaid expansion led to a large, sudden increase in the number of individuals eligible for various health care needs. This sudden increase in demand for health services lead to initial hypotheses regarding hospitals’ ability to handle this demand. The first analysis examined hospital average length of stay (LOS) using a linear mixed-effects model. Length of stay was modeled longitudinally between 2013 and 2015 to determine if significant changes in the slope of LOS could be detected after expansion (2014). Separate …

Changes In Cancer Diagnosis And Survival In The United States During The Covid-19 Pandemic, Justin T. Burus

Theses and Dissertations--Epidemiology and Biostatistics

The COVID-19 Pandemic led to global societal disruptions as political leaders and public health authorities attempted to control the spread of the newly discovered SARS- CoV-2 virus. While these measures were designed to lessen morbidity and mortality from a novel pathogen, their impact was also felt in many other, often unintended ways. The purpose of this dissertation is to use cancer surveillance research methods to examine the association between COVID-19 Pandemic-related disruptions and changes in the normal diagnosis and care of cancer in the United States.

The first two studies of this dissertation analyzed reductions in cancer diagnoses in the …

A Comprehensive Exploration Of Stress And Depressive Symptoms In Farm Populations, Julie C. Derringer

Theses and Dissertations--Nursing

High rates of depression and suicide continue to be a concern, despite four decades of growing research into the mental health of farmers. Most farmers have an awareness of a need for improved mental health, but a lack of knowledge persists. As agricultural production demands increase and the number of family farms decreases, the stress placed upon farmers to support the food chain is higher than ever. Understanding the association between farm demands and resources among farmers is key for the development and implementation of programs to decrease occupational stress and depressive symptoms to improve mental health outcomes across farming …

Using Hyperactive Shp-2 Mutants, A Phosphatase, To Identify Interactions With The Rna Helicase Ddx3, Devin Montgomery

Theses and Dissertations--Pharmacy

Protein-protein interactions are critical in cellular signaling pathways. This project investigates binding interactions between SHP-2, a tyrosine phosphatase, and DDX3, an RNA helicase. There is a specific focus on the impact that gain-of-function SHP-2 mutations may impact binding to DDX3 via conformational change. Using immunoprecipitation protocols as well as western blotting we were able to provide insights into SHP-2 molecular mechanisms and subsequent binding to DDX3.

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 …