Medicine and Health Sciences Commons^™

Investigating Non-Functional Overreaching In Special Operations Tactical Training, Jeremy Alan Ross

Theses and Dissertations--Rehabilitation Sciences

Special Operations Forces (SOF) tactical training requires high levels of physical performance and psychological resilience. This training is often characterized by extreme temperatures and environments, extremely high levels of physical activity and large caloric deficits. As such, SOF personnel follow intense strength and conditioning (S&C) programs to enhance a wide range of athletic abilities. Such programs rely on a balance between training stress and recovery to allow for gradual improvement in physical ability over time, however it is unknown how to quantify tactical training stress in the context of a training program. This dissertation explores evidence related to how this …

Early Changes In Inflammation-Related Proteins In The Cerebrospinal Fluid And Plasma Of Patients With Aneurysmal Subarachnoid Hemorrhage, David J. Braun, Kevin W. Hatton, Justin F. Fraser, Robert M. Flight, Hunter N. B. Moseley, Caleb S. Bailey, Josh M. Morganti, Bingqing Zhang, Ishara S. Ariyapala, Tae K. Kim, Linda J. Van Eldik

Sanders-Brown Center on Aging Faculty Publications

Background

Aneurysmal subarachnoid hemorrhage (aSAH) is a relatively uncommon but high mortality form of stroke that can result in long-lasting disability. A better understanding of key neuroinflammatory changes during the early phase (< 72 h) may provide potential avenues of treatment.

Methods

In an attempt to understand these early changes, we recruited 7 aSAH patients for profiling of longitudinal plasma and cerebrospinal fluid (CSF) proteins at up to 72 h post injury. We additionally compared this to control plasma obtained previously from healthy elderly volunteers. Using the Alamar Biosciences NULISAseq platform, we obtained a comprehensive picture of early peripheral and central inflammatory changes after injury.

Results

This study …

Nicorandil Treatment Improves Survival And Spatial Learning In Aged Granulin Knockout Mice, Dana M. Niedowicz, Wang-Xia Wang, Paresh Prajapati, Yu Zhong, Shuling X. Fister, Colin B. Rogers, Pradoldej Sompol, David K. Powell, Indumati Patel, Christopher M. Norris, Kathryn E. Saatman, Peter T. Nelson

Sanders-Brown Center on Aging Faculty Publications

Mutations in the human granulin (GRN) gene are associated with multiple diseases, including dementia disorders such as frontotemporal dementia (FTD) and limbic-predominant age-related TDP-43 encephalopathy (LATE). We studied a Grn knockout (Grn-KO) mouse model in order to evaluate a potential therapeutic strategy for these diseases using nicorandil, a commercially available agonist for the ABCC9/Abcc9-encoded regulatory subunit of the “K⁺ATP” channel that is well-tolerated in humans. Aged (13 months) Grn-KO and wild-type (WT) mice were treated as controls or with nicorandil (15 mg/kg/day) in drinking water for 7 months, then tested for neurobehavioral …

Gait Variability As A Marker Of White Matter Integrity In Individuals With Down Syndrome, Elizabeth M. Leach, David K. Powell, Amanda C. Glueck, Elizabeth Head, Moaz W. Ibrahim, Amelia J. Anderson-Mooney, Kathryn L. Van Pelt, Jordan P. Harp, Frederick A. Schmitt, Ahmed A. Bahrani

Sanders-Brown Center on Aging Faculty Publications

Introduction: Individuals with Down syndrome (DS) face a significant risk of neurodegeneration, and gait variability may serve as a clinical biomarker of neurological health. This longitudinal parent substudy aimed to explore relationships between gait, white matter (WM) integrity, and cognitive function in DS.

Methods: The associations were investigated between magnetic resonance imaging diffusion tensor imaging (DTI), cognition, and self-paced gait data from 22 DS participants (mean age ± SD 37 ± 7.5 years).

Results: DTI measures, such as lower fractional anisotropy (FA) and higher mean diffusivity, were correlated with greater step time variability but not normalized velocities. Lower cognitive scores …

Disrupted Calcium Dynamics In Reactive Astrocytes Occur With End Feet–Arteriole Decoupling In An Amyloid Mouse Model Of Alzheimer’S Disease, Blaine Weiss, John C. Gant, Ruei-Lung Lin, Jenna L. Gollihue, Colin B. Rogers, Susan D. Kraner, Edmund B. Rucker, Yuriko Katsumata, Yang Jiang, Peter T. Nelson, Donna M. Wilcock, Pradoldej Sompol, Olivier Thibault, Christopher M. Norris

Sanders-Brown Center on Aging Faculty Publications

While cerebrovascular dysfunction and reactive astrocytosis are extensively characterized hallmarks of Alzheimer's disease (AD) and related dementias, the dynamic relationship between reactive astrocytes and cerebral vessels remains poorly understood. Here, we used jGCaMP8f and two-photon microscopy to investigate calcium signaling in multiple astrocyte subcompartments, concurrent with changes in cerebral arteriole activity, in fully awake 7- to 8-month-old male and female 5xFAD mice, a model for AD-like pathology, and wild-type (WT) littermates. In the absence of movement, spontaneous calcium transients in barrel cortex occurred more frequently in astrocyte somata, processes, and perivascular regions of 5xFAD mice. However, evoked arteriole dilations (in …

Knee Health Is A Major Determinant Of Mobility Across The Healthspan, Brandon M. Peoples, Kenneth Harrison, Michael A. Samaan, Christopher B. Mobley, David T. Redden, Jaimie A. Roper

Kinesiology and Health Promotion Faculty Publications

Knee health constitutes a pivotal determinant of locomotor function and overall mobility throughout the healthspan. Impairments in knee function lead to a series of biomechanical and physiological alterations that pose substantial public health challenges and economic burdens worldwide. This review synthesizes evidence that delineates the complex and multifaceted relationship between knee health and mobility, emphasizing the interplay across various domains in adult populations. Knee health is conceptualized as a dynamic, interconnected system whereby structural integrity, neuromuscular mechanisms, biomechanical adaptations, and functional mobility are intricately interrelated through cascades of mechanistic processes operating across different temporal stages. A comprehensive understanding of these …

Chronic Alcohol Consumption Induces Phenotypic And Functional Alterations Consistent With A Hyper-Inflammatory State In Peripheral Blood Mononuclear Cell-Derived Microglia In A Rhesus Macaque Model, Hami Hemati, Madison B. Blanton, Heather E. True, Jude Koura, Rupak Khadka, Kathleen A. Grant, Ilhem Messaoudi

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Alcohol-induced dysregulation of microglial activity is associated with neuroinflammation, cognitive decline, heightened risk for neurodegenerative diseases, alcohol dependence, and escalation of alcohol drinking. Given the challenge of longitudinally sampling primary microglia, we optimized an in vitro method to differentiate peripheral blood mononuclear cells (PBMC) from rhesus macaque (RM) into induced microglia-like cells (RM-iMGLs). The RM-iMGLs displayed transcriptional profiles distinct from monocyte progenitors and closely resembling primary microglia. Notably, morphological features showed that differentiated RM-iMGLs derived from subjects with chronic alcohol consumption (CAC), while bigger, exhibited a bipolar-like morphology. Additionally, dysregulation in key inflammatory and regulatory markers, along with increased baseline …

Adapting A Mobile Health Intervention To Improve Prep Adherence Among Young Black Msm In Fulton County, Georgia, Kassidy Maust

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

Young Black men who have sex with men (YBMSM) in the southern United States, particularly in Fulton County, Georgia, face disproportionately high rates of HIV and unique structural barriers to pre-exposure prophylaxis (PrEP) uptake and adherence. Sustained adherence among YBMSM remains low due to intersecting structural, social, and behavioral barriers. To address these disparities, this paper presents an adapted implementation of the evidence-based M-Cubed (Mobile Messaging for Men) mHealth intervention. Prior studies of M-Cubed and similar mHealth interventions have shown promising outcomes in increasing PrEP adherence among Black MSM populations. The adapted intervention integrates culturally tailored messaging specific to behaviors …

Air Pollution Exposures And Cognitive Function Among Older Americans, Clarisse Nyondo Okoma

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

Background: New findings indicate that environmental factors, such as air pollution, could contribute to cognitive decline among older adults. Nonetheless, extensive longitudinal studies in the U.S. investigating this connection are few and far between.

Objective: This study assessed the relationship between long-term exposure to ambient air pollutants and cognitive function in older adults in the United States.

Methods: We examined data from the Health and Retirement Study (2010-2018), which included 234,250 observations from adults aged 50 and older. Cognitive performance was evaluated based on immediate and delayed word recall, a 27-point cognitive summary score, backward from 20, and …

Implementing An Opioid Overdose Education And Naloxone Distribution (Oend) Program Among Law Enforcement Officers In Lee County, Ky, Keelie Jolly

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

This grant proposal describes an implementation strategy for introducing an OEND training program among law enforcement officers (LEOs) to reduce opioid overdose deaths. The goal of the project is to increase LEOs' awareness and knowledge of opioid overdose and Naloxone administration and usage of Naloxone.

Rct Pre-Post Training Analysis Of The Vipcorps Maternal Mortality Prevention Course With A Focus On Intimate Partner Violence (Ipv), Rose A. Wood

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

Maternal mortality rates rob families across the U.S. of a mother figure, and each death is preventable. The U.S. has the highest maternal mortality rate of high-earning countries. This study assesses the effects of the VIPCorps program, a course on the top 3 risk factors of maternal mortality, on improving knowledge and attitudes towards victims of IPV. Students in helping professions at the University of Kentucky (n = 223) were recruited via on campus advertising and remotely allocated to either the VIPCorps program or a mock maternal mortality training control. Generalized linear modeling was used to estimate the difference in …

Improving End-Of-Life Care: A Nursing Education Initiative, Spring C. Kingsley

DNP Projects

Background: This study addresses the gap in education and training for medical intensive care unit (MICU) nurses regarding the care of hospice patients. The traditional medical model of healthcare prioritizes illness treatment, often leading to inadequate end-of-life support and increased hospitalization during patients' final days. The rise of in-hospital hospice programs, or scatter-bed hospice models, highlights the need for nurses to enhance their skills in providing end-of-life compassionate care. The MICU at the University of Kentucky’s Chandler Hospital serves as a focal point for this initiative, given its role in caring for critically ill patients who require hospice attention.

Purpose: …

Demonstration Of An Enhanced Dosing Pattern For Debulking Large And Bulky Unresectable Tumors Via Differential Hole-Size Spatially Fractionated Radiotherapy, Joshua Misa, William St. Clair, Damodar Pokhrel

Radiation Medicine Faculty Publications

Purpose/objective

We propose a novel lattice deployment for spatially fractionated radiotherapy (SFRT) treatments. In this approach, a larger diameter high-dose sphere is centrally placed in the bulky tumor mass and surrounded by smaller diameter high-dose spheres.

Materials/methods

Thirty SFRT patients (10 head and neck [HN], 10 abdominal/pelvis, and 10 chest/lung cases) treated with an MLC-based crossfire method were retrospectively analyzed. Eleven differential hole-size lattice patterns were benchmarked against the clinically delivered SFRT plans (1 cm diameter cylinders, 2 cm spacing) and the standard uniform lattice pattern (1.5 cm diameter spheres, 3 cm spacing). These patterns varied in core diameter (C: …

In Vitro Α/Β Ratio Variations In Cervical Cancer, With Consequent Effects On Equivalent Dose In 2 Gy Fraction In High-Dose-Rate Brachytherapy, Cameron Thayer-Freeman, Brien Washington, Denise Fabian, Dennis C. Cheek, William St. Clair, Mark E. Bernard, Wei Luo

Radiation Medicine Faculty Publications

Purpose: To determine the distributions of published α/β values measured in vitro and the resulting uncertainties in the equivalent dose in 2 Gy fractions (EQD ₂ ) when applied to high-dose-rate brachytherapy (HDR-BT) for cervical cancer.

Methods and Materials: An analysis of 98 published α/β values from 31 papers was conducted, spanning 23 cervical cancer cell lines. Values were further divided into squamous cell carcinoma and adenocarcinoma histologies. Probability distributions were fit to histograms using the bootstrapped Kolmogorov-Smirnov goodness-of-fit test. Both average and most probable α/β values for cervical cancer were determined. The probability distributions were then applied to three …

Innovative Biomechanical And Engineering-Based Assessments Of Hip Mechanics In Individuals With Hip-Related Pain, Holly M. Stanze

Theses and Dissertations--Kinesiology and Health Promotion

Individuals with hip-related pain exhibit altered movement patterns, and worse fear of movement (kinesiophobia), compared to asymptomatic controls. Exacerbation of hip pain during movement and the role of hip symptom duration may help further our understanding of specific movement patterns that are associated with hip-related pain. A better understanding of the potential connections between hip-related symptom duration, kinesiophobia, hip pain during movement, and lower limb mechanics in those with hip-related pain may allow for more efficient referrals to clinicians and lead to more effective rehabilitation. In addition, the impact of hip-related pain on intra-articular hip loading patterns is not well …

Psychological Impacts In Exercise Riders And Professional Jockeys Following Injury, Kelley M. Renner

Theses and Dissertations--Kinesiology and Health Promotion

One of the most well-known equestrian sports, horse racing, is not only a cornerstone of Kentucky’s economy, but also a vital part of its culture, with professional jockeys playing an essential role in the local communities and traditions that define the state. Despite its popularity and financial impact, mental health challenges within the sport have continually been shrouded in silence and ignored in research (Ball et al., 2007). Equally concerning is the high injury prevalence, and psychological impact of these injuries (e.g., psychological distress, depression, anxiety, loss of identity, and self-esteem (King et al., 2022; Losty et al., 2019; McConn-Palfreyman …

The Effects Habitual Training Shoe Use Has On Running Economy When Transitioning To High Performance Running Shoes, Dalton C. Harris

Theses and Dissertations--Kinesiology and Health Promotion

Background: The recent increase in popularity of minimal shoes in endurance running is linked to potential improvements in running economy and reduced injury risk. However, high performance running shoes, specifically designed to improve running economy remain the fastest shoe to wear when racing. Purpose: Knowing this, the aim of this paper is to examine whether or not the habitual use of minimal shoes increases the benefits of the high performance shoes. This will guide practitioners and athletes when establishing shoe rotations and training plans during race preparation. Methods: The study consisted of 4 sessions: Sessions 1 and 2 were maximal …

Proximity And Density Of Tobacco Retail Locations To Kentucky Schools And The Relationship To Youth Perceptions Of Harm And Susceptibility To E-Cigarette Use, Hannah Cardona

Theses and Dissertations--Kinesiology and Health Promotion

Purpose: To explore the potential relationship between tobacco retailer proximity/density around Kentucky elementary, middle, and high schools, and students’ perceptions, perceived norms, susceptibility to, and use of e-cigarettes. Design: A mixed-methods analysis of youth’s self-reported survey results and geographical data. Setting: 106 Kentucky elementary, middle, and high schools which participated in #iCANendthetrend’s tobacco education program between September 2023 and May 2024. Subjects: Convenience sample of students from Ky schools (N = 7,823) Measures: Items assessing e-cigarette use, susceptibility, perceptions, and perceived norms. Analysis: ANOVA tests used to compare responses of elementary, middle, and high school students. Chi-squared tests were used …

You’Re Too Slow! Self-Selected Volitional Efforts Reveal Unexploited Neuromuscular Reserve Capacity Compared To Maximal Efforts During Fatiguing, Load Equated Resistance Exercise, Brian Benitez

Theses and Dissertations--Kinesiology and Health Promotion

This investigation examined how movement intent influences neuromuscular excitation strategies during fatiguing resistance exercise, comparing maximal intended concentric efforts versus self-selected volitional efforts during load-equated Smith machine back squat exercise to quantify reserve capacity and characterize underlying neuromuscular mechanisms. Twenty-three resistance-trained participants (12 males, 11 females) completed a repeated-measures design, with replication, across six visits, performing smith machine back squat repetitions-to-failure at 70% 1RM under maximal intent (accelerate rapidly) and volitional intent (self-selected effort) conditions. Maximal voluntary isometric contractions used rapid (instantaneous 10-second effort) and ramp (5-second build-up, 5-second maximal) protocols. Surface electromyography (sEMG) was recorded from vastus lateralis and …

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.