Medicine and Health Sciences Commons^™

Enlarged Perivascular Spaces Are A Clinically Relevant Neuroimaging Biomarker Of Cerebral Small Vessel Disease, Timothy Justin Libecap

Theses and Dissertations--Neuroscience

Vascular contributions to cognitive impairment and dementia (VCID) represents the intersection between cerebrovascular disease and cognitive decline. Cerebral small vessel disease (cSVD) is an important risk factor that may precede the onset of VCID by years. cSVD is characterized by in-vivo neuroimaging biomarkers including enlarged perivascular spaces (ePVS). PVS are the site of interchange between interstitial fluid (ISF) and cerebrospinal fluid (CSF) which is believed to play a role in the removal of brain waste. Reduced clearance may lead to enlargement of the PVS and subsequent accumulation of toxic solutes characteristic of neurodegeneration. Given the presence of ePVS in brain …

The Role Of Dystrophic Microglia In Aging And Disease, Ryan K. Shahidehpour

Theses and Dissertations--Neuroscience

Microglia are the primary immune cells of the central nervous system and are crucial in maintaining homeostasis and defense from disease and injury in the brain. Recent genome-wide association studies (GWAS) have also highlighted microglia as a central player in Alzheimer’s disease (AD). However, the mechanisms of microglia’s influence are poorly understood. Traditionally, microglial subtypes characterized physiologically as “reactive” or “activated” have been linked with disease and injury in the brain. However, morphologically, a recently described microglia category known as “dystrophic,” characterized structurally by fragmented processes and cytoplasmic decay is believed to be more strongly associated with aging and neurodegeneration. …

What’S Harm Reduction Got To Do With It? A Study Of The Implementation Of Substance Use Management Practices Among A Sample Of U.S. Domestic Violence Programs, Stephanie H. Ratliff

Theses and Dissertations--Social Work

Domestic violence programs are essential resources for survivors of intimate partner violence (IPV). Programs offer services that go beyond providing safety and shelter. To improve outcomes, program staff have expanded services to meet the needs of survivors. One population of survivors that has gained attention in the peer-reviewed literature is survivors who use substances (SWUS). These survivors have unique needs and are at increased risk of IPV due to substance misuse. Research about the support available to SWUS after they access shelter is scarce. Using cross-sectional data from a national sample of 97 U.S. domestic violence programs, this study describes …

The Performance Of Marginal Modeling Methods For Rare Events With Application To Opioid Overdose Mortality And Morbidity, Shawn Nigam

Theses and Dissertations--Epidemiology and Biostatistics

Opioid misuse is a nationwide epidemic, with Kentucky having one of the highest opioid overdose-related fatality rates across all US states. These rates have increased significantly over the past decade, with particularly large increases during the COVID-19 pandemic. This dissertation aims to study the behavior of these increases and the methods for the marginal modeling of count outcomes related to opioid overdose.

Opioid overdose-related fatality rates in Kentucky increased significantly during the COVID-19 pandemic. In this chapter, we characterize the changes in opioid overdose fatality rates in Kentucky and identify associations between potential factors and fatality rates. County-level opioid overdose …

Intentions To Seek Mental Health Services Among Nursing Students In The United States: The Impact Of Adverse Childhood Experiences And Psychological Distress, Zainab Almogheer

Theses and Dissertations--Nursing

Supporting the mental health of university/college students is a crucial issue facing institutions of higher learning in the U.S. A web-based survey encompassing 196 campuses in the U.S. found that rates of diagnosed mental illness among college students has significantly increased in the last decade from 21.7% in 2007 to 35.5% in 2017 (Lipson et al., 2019). Despite the availability of mental health services within universities/colleges, students with mental health problems do not often utilize these services. Recognizing the significance of assessing the mental health of nursing students is paramount, as evident from a study where 35% of 170 participants …

Health Beliefs, Facilitators And Barriers To Engaging In Blood Glucose Screening Of Adults In Saudi Arabia, Fatema Alsada

Theses and Dissertations--Nursing

Diabetes has reached an epidemic level in Saudi Arabia with a prevalence of 19%. Saudi Arabia currently spends more than $7 billion on diabetes-related health care per year. Type 2 diabetes is preceded by a prediabetes state during which preventative measures can prevent or delay diabetes onset. Blood glucose screening is a method of identifying people with prediabetes. Encouraging people to engage in blood glucose screening will identify those who will benefit from diabetes prevention strategies. The purpose of this dissertation was to explore the knowledge, health beliefs, and perceived barriers and facilitators regarding engaging in blood glucose screenings among …

Investigating A New Drug Target In Alzheimer’S Disease: Nox2, Tiffany Adams

Theses and Dissertations--Pharmacy

Introduction: Alzheimer’s disease (AD) is a neurodegenerative disease with neuropathological changes in the blood-brain barrier that offers possible therapeutic targets. Oxidative stress is one driving factor for AD. NADPH oxidase 2 (NOX2) in the capillary endothelium produces reactive oxygen species, leading to oxidative stress-mediated blood-brain barrier dysfunction. We hypothesized that using a specific NOX2 inhibitor, PhoxI2, has the potential to reduce reactive oxygen species and repair amyloid-β (Aβ)-driven blood-brain barrier leakage in an AD mouse model.

Methods: For this study, 5xFAD (Familiar Alzheimer Disease) mice were treated with vehicle or PhoxI2, a NOX2 inhibitor. Techniques utilized were Enzyme-Linked Immunosorbent Assay …

Design Of Kappa Opioid Receptor Agonists For Potential Treatment Of Multiple Sclerosis, Lindsay Kornberger

Theses and Dissertations--Pharmacy

Multiple Sclerosis (MS) is a neurodegenerative disease of the central nervous system characterized by demyelination and neuroinflammation. There is currently no cure for MS. There is a critically unmet need for the development of pharmacotherapies that can induce remyelination promoting both repair and recovery. The kappa opioid receptor (KOR) has been identified as a potential target for the development of remyelinating pharmacotherapies. KOR activation has been shown to promote functional recovery and remyelination preclinically. However, typical KOR agonists like U50,488 have limitations such as sedation and dysphoria limiting their use. This necessitates further development of new KOR agonists that maintain …

Sensitizing Keap1 Loss Non-Small Cell Lung Cancer To Artesunate Anti-Cancer Activity, Keng Hee Peh

Theses and Dissertations--Pharmacy

Lung cancer is the global leading cause of cancer related death. Non-small cell lung cancer (NSCLC) accounts for 80% of lung cancer diagnoses conferring a significant disease burden. However, certain mutations in tumor suppressors such as Kelch-like ECH-associated protein 1 (KEAP1) confers resistance to standard of care therapy in NSCLC. KEAP1 is known to regulate multiple cellular processes such as oxidative stress response and anti-apoptotic pathways. Furthermore, KEAP1 loss of function in NSCLC is associated with poorer clinical outcomes and there are no currently approved therapies for KEAP1 loss NSCLC and represents an unmet clinical need. Artesunate (Art) demonstrated anti-cancer …

Inhibiting Pi3k/Akt To Enhance Brain Uptake Of Anticancer Agents In Glioblastoma, Louis Rodgers

Theses and Dissertations--Pharmacy

Glioblastoma (GBM) is the deadliest and most common malignant CNS tumor. Despite advances in understanding its biology and the development of targeted therapies, effective treatment options remain limited. As a result, patient survival rates are dismal, with a 5-year survival rate of only 6.8% and an overall survival of less than two years. This poor outcome is partly due to our inability to treat GBM cells that infiltrate the whole brain. Focal treatments like surgery and radiotherapy alone are insufficient due to these invasive tumor cells. Therefore, chemotherapy following resection and irradiation of the primary tumor is essential to eliminate …

Repolarizing Tumor-Associated Macrophages In Ovarian Cancer: A Novel Immunotherapeutic Approach, David Schweer

Theses and Dissertations--Clinical and Translational Science

Ovarian cancer, recognized for its high lethality and resistance to conventional immunotherapies, mandates innovative strategies to confront its intricate challenges. The tumor microenvironment (TME), orchestrated by tumor-associated macrophages (TAMs), assumes a pivotal role in disease progression, rendering TAMs an appealing therapeutic target. This study endeavors to explore the prospect of repolarizing TAMs from a protumor M2 phenotype to an antitumor M1 state, employing M1 macrophage-derived vesicles (MEVs) as a groundbreaking immunotherapeutic approach.

The primary objective is to investigate the capacity of M1 MEVs to repolarize M2 macrophages in vitro towards an anti-tumor M1-like phenotype. By inducing human macrophages to adopt …

Developing Radiosensitizers To Enhance Radiotherapy In Treating Gastroenteropancreatic Neuroendocrine Tumor, Zeta Chow

Theses and Dissertations--Clinical and Translational Science

Gastroenteropancreatic Neuroendocrine Tumor (GEP-NET) is a heterogeneous group of malignancies arising from multipotent neuroendocrine stem cells in the gastrointestinal tract. The incidence of GEP-NET continues to rise, possibly due to the advancement of imaging and biomarkers available for diagnosis. However, even though the majority of patients are diagnosed with low-grade and localized disease, a significant percentage of patients present with advanced-stage metastatic disease with poor prognosis in months to a few years. These advanced-stage GEP-NET patients can also present with a variety of debilitating symptoms that significantly impact their quality of life. The role of palliative-intent surgery is limited, and …

Evaluation Of The Cellular And Physiologic Impact Of Mitomycin C On Colon Cancer, Hannah Mcdonald

Theses and Dissertations--Clinical and Translational Science

Cytoreductive surgery (CRS) and heated intraperitoneal chemotherapy (HIPEC) with Mitomycin C (MMC) has more than doubled the overall and disease-free survival in patients with peritoneal metastases (PM) due to colorectal cancer (CRC) over the past two decades. Although MMC is the most used HIPEC drug for PM due to CRC, dosing protocols vary dramatically between and within institutions across the world. Additionally, little is known about the impact of hyperthermia and MMC on intracellular pathways for CRC. The aim of this work is to determine the optimal dosing strategy in the clinical application of MMC and hyperthermia for treatment of …

Advancing Dysphagia Screening: A Comparison Of Patient-Reported Outcome Measures And Bolus-Driven Screenings In Aspiration Prediction, Arica Amie Rusco

Theses and Dissertations--Communication Sciences and Disorders

It is known that dysphagia impacts an individual’s health and quality of life. Due to this, early identification of dysphagia is crucial. There are many different dysphagia screening tools with no consensus. This study aimed to compare the two most frequently used dysphagia screenings, a patient-reported outcome measure (PROM), the EAT-10, and bolus-driven swallow screening, the Yale Swallow Protocol, to determine if one tool is superior in aspiration prediction on a videofluoroscopic swallow study (VFSS). This study also aimed to discover the best cutoff score on the EAT-10 for aspiration prediction. A total of 66 participants were recruited after physician …

The Effects Of Exercise-Based Voice Therapy On Swallowing Outcomes: A Pilot Study Framework, Jenna F. Johnson

Theses and Dissertations--Communication Sciences and Disorders

In a 2019 study analyzing dysphonic patients in relation to coexisting dysphagia, approximately 11.8% of clients receiving treatment for voice disorders reported difficulty swallowing. However, the literature exploring the use of voice exercises to improve swallow function is limited to a small amount of voice treatment approaches, which does not reflect the wide range of evidence-based treatment approaches that may be prescribed for treatment of one’s voice complaints. This project proposes a descriptive study that would identify if completion of prescribed voice therapy exercises has implications on swallowing function in clients with co-occurring voice and swallow impairments. A pilot study …

The Relationship Between Sleep, Physical Activity, And Musculoskeletal Injury, In Us And Saudi College Students, Abdulaziz Hasan Alameer

Theses and Dissertations--Rehabilitation Sciences

According to the National Sleep Foundation, individuals should sleep 7-9 hours every night. Recently, insufficient or poor sleep has been linked to diabetes, cardiovascular illness, stroke, obesity, and Alzheimer's disease. Insufficient sleep for college students can negatively impact academic performance and mental health. In addition, especially for collegiate athletes, there is evidence that insufficient sleep is associated with an increased risk of musculoskeletal injury. However, it is uncertain if the link between sleep and injury varies between populations, types of individuals (athletes vs non-athletes), sports or types of exercise, or training volume. Despite the health risks of inadequate sleep, up …

Using Inertial Measurement Units (Imus) To Assess Fatigue-Related Changes In Running: Applications In Training Load Management, Reiley Thomas Bergin

Theses and Dissertations--Rehabilitation Sciences

The inertial measurement unit (IMU) is the most researched wearable technology in running. Yet, few studies have validated IMU-derived measures against accepted laboratory standards, such as three-dimensional (3D) motion capture and force plates. IMUs have the potential to provide information that can guide training load management decisions; however, no study has explored their capability to assess fatigue-related changes in running across consecutive days of training. Therefore, the purpose of this project was to evaluate the validity and reliability of IMU-derived measures and assess their capability for detecting fatigue-related changes in running in the days following an intensified training bout. The …

The Critical Need For Early Language Access For Deaf And Hard Of Hearing Children, Kinya D. Embry-Wright

Theses and Dissertations--Rehabilitation Sciences

According to the American Speech-Language-Hearing Association (ASHA), speech-language pathologists (SLPs) are referred to as the experts of communication (ASHA, n.d.) utilizing their specialized training, extensive education, and clinical expertise to work with individuals across the lifespan with a variety of different speech and language delays, disorders, and deficits. However, when working with deaf or hard of hearing (DHH) children, there is often precedent given to speech and listening (M. L. Hall et al., 2019). For example, ASHA only recently updated their DHH portal to include American Sign Language (ASL), though they still list it on some webpages as an Augmentative …

Exploration Of Burn Survivors’ Experiences With Nutrition During The Rehabilitation Phase Of Burn Injury Recovery: A Qualitative Study, Alyaa M. Zagzoog

Theses and Dissertations--Rehabilitation Sciences

Approximately 500,000 people in the United States are affected by a burn injury and seek care every year. With medical innovation, however, the burn injury survival rate has increased to 97% in the United States. Burn survivors undergo two phases of recovery: acute and rehabilitation.With advances in burn treatment and care, the focus has shifted from the expectation of survival to improving outcomes. Nutritional care, including assessment and education, plays a major role in burn survivors’ wellness, facilitating wound healing and promoting recovery, but nutritional guidelines and polices appear limited during the rehabilitation phase,with literature suggesting nutritional assessment has historically …

Abl1/2 And Ddr1 Cooperate To Stabilize Braf/Craf To Drive Erk1/2 Reactivation And Promote Mek Inhibitor Resistance In Nras-Mutant Melanomas, Anastasia Lyon

Theses and Dissertations--Pharmacology and Nutritional Sciences

This study addresses the escalating incidence of NRAS-mutant melanomas, a type of skin cancer lacking FDA-approved targeted therapies. Despite ongoing research targeting the RAF/MEK/ERK pathway, existing drugs fail to enhance progression-free survival due to acquired resistance. This project identifies a novel role for ABL1/2 and DDR1 kinases in driving drug resistance and proliferation of NRAS-mutant melanoma cells. ABL1/2 and DDR1 cooperate to promote RAF homodimerization and protein stability in order to reactivate MEK/ERK signaling to drive MEK1/2 inhibitor (MEKi) resistance and promote survival of resistant cells. By targeting ABL1/2 and DDR1 with nilotinib, a FDA-approved anti-leukemic inhibitor, we …

The Function Of The Insulin Receptor In Liver Subcell Types And Its Dichotomous Role In Hepatic Dysfunction, Wang-Hsin Lee

Theses and Dissertations--Pharmacology and Nutritional Sciences

Insulin resistance and metabolic dysfunction-associated steatotic liver disease (MASLD) have become significant health issues worldwide. Increased prevalence of hepatic insulin resistance and MASLD worsens the threat of its progressive complications, such as liver fibrosis, which can lead to cirrhosis and death if left untreated. Treatments for MASLD-induced liver fibrosis are mainly insulin sensitizers. However, activating insulin signaling leads to a higher death rate in end-stage liver fibrosis. This dissertation discusses the emerging insights into hepatic insulin resistance and potential treatment targets in the heme degradation pathway for reversal. We also investigated the mechanisms that the insulin receptor (INSR) regulates in …

Exenatide As Chronopharmacotherapy For T2dm Associated Complications: Targeting Nondipping Blood Pressure And Sleep Insufficiency, Aaron Chacon

Theses and Dissertations--Pharmacology and Nutritional Sciences

Although largely impacted by age, race and ethnicity, and socioeconomic factors, Type 2 Diabetes Mellitus (T2DM) is primarily driven by obesity, currently affecting ~30 million in the U.S and ~463 million globally. T2DM carries numerous complications, including high prevalence of hypertension and nondipping blood pressure (BP), sleep insufficiency and fragmentation. Nondipping BP is an inadequate drop in BP (≤ 10%) during sleeping hours compared with waking hours. Lending to this, sleep disturbance acts as both precursor and consequence of metabolic dysregulation, greatly impacting circadian rhythmicity. To model these conditions, we utilized diabetic (db/db) mice. These mice carry a point mutation …

Cell-Based Cardiac Repair And The Natural Cardiac Healing In Regenerative Adult Mammal, Hsuan Peng

Theses and Dissertations--Pharmacology and Nutritional Sciences

Heart failure (HF) following myocardial infarction (MI) remains a significant global health concern, with the initial ischemic injury often leading to microvascular damage and infarct expansion, exacerbating the overall cardiac impairment. Despite extensive research, there are currently no effective therapies to limit myocardial damage post-MI, resulting in a substantial number of patients progressing to HF. Stem cell therapy has emerged as a promising approach to modulate cardiac injury and promote healing. However, clinical trials have shown only modest success, underscoring the need for improved strategies to enhance efficacy. Additionally, the lack of significant ventricular regeneration highlights the necessity of targeting …

The Delineation Of Platelet Pathology In Cardiometabolic Disease, Chi Peng

Theses and Dissertations--Pharmacology and Nutritional Sciences

Obesity is a multifactorial disease with many comorbidities leading to multiorgan dysfunction. Current studies point towards dysregulation of platelet signaling as a driver for increased risk of cardiovascular disease and stroke. The exact mechanisms remain elusive due to the complex interplay of factors involved, warranting the need to further understand how platelets are affected. Our preliminary data evaluating changes in platelet and coagulation parameters from bariatric patients showed that obesity did not affect platelet count or clotting time as demonstrated in INR values. However, female patients had increased bleeding events before surgery that were decreased after surgery. Due to limitations …

Characterization Of Bowel Dysfunction After Spinal Cord Injury In Mice, Olivia Wireman

Theses and Dissertations--Physiology

Most individuals who suffer a spinal cord injury (SCI) will experience some form of bowel dysfunction. Trauma to the spinal cord can result in severe constipation and/or incontinence, otherwise known as neurogenic bowel. Constipation requires extensive bowel routines typically involving the help of another person. Still, many living with SCI are hospitalized due to bowel complications such as fecal impaction. While neurogenic bowel has been well characterized in the clinic, pre-clinical models of neurogenic bowel after SCI are still in development. Most pre-clinical studies in bowel dysfunction after SCI are published in rat models. Studies existing in mice, to our …

Maternal-Adolescent Communication About Sex And Risky Sexual Behaviors: A Cross-Cultural Comparison Of Czech, Spanish, And Taiwanese Youth, Mckinley Hall

Theses and Dissertations--Family Sciences

This present study aimed to test the relationship between perceived maternal-adolescent communication about sex and risky sexual behaviors, while also considering the links between perceived maternal-adolescent closeness and maternal-adolescent conflict with risky sexual behaviors, across three culturally distinct countries, namely the Czech Republic (N=878, mean age of 17.93), Spain (N =1024, mean age of 18.79), and Taiwan (N =1443, mean age of 16.48). Samples of adolescents from each country were used and statistical analyses were conducted to test the hypothesized relationships. Based on path analysis carried out on each sample, the results revealed that Czech adolescents reported the highest levels …

Nutrient Profile Assessment Of A Meal Program Impact On Older Adults' Diet Quality And Food Security Status, Millicent Yaa Gyasiwaa Ms

Theses and Dissertations--Nutrition and Food Systems

The rise in food insecurity globally has ignited institutions and organizations to implement policies and programs to reduce the burden on vulnerable people including older adults and people living in underserved areas. Though programs such as congregate, home-delivered meals, and pantries have been initiated to contribute to reducing food insecurity the nutrient content of these meals including recovered meals and their effect on food security status, food quality, and health has not been widely studied. The current study, Meals on Wings (MOW), assessed the nutrient profile of the free meals offered 4 times per week for 3 months, from May …

Acting On Routine Outcome Monitoring, Virginia Courtney

Theses and Dissertations--Family Sciences

This thesis explores the application of an Acceptance and Commitment Therapy (ACT) informed approach in achieving clients’ therapeutic objectives via systematically tracking client progress over the therapy process. The study utilized the Marriage and Family Therapy Practice Research Network (MFT-PRN), a specific tool that aids the tracking of therapy progress, to gather relevant client data. The data consisted of therapy progress for 27 individuals the author worked with, 1,001 individuals from the Individual Relational and Finance Therapy Clinic, and 4,424 individuals from the MFT-PRN-Network. Upon collecting this data, progress trajectories were generated using Microsoft Excel to compare the author’s clients’ …

Division Of Labor And Relationship Satisfaction: Examining The Mediating Role Of Self Esteem, Ellen Keith

Theses and Dissertations--Family Sciences

As a result of feminist movements, rejections of gender roles, and changing economic conditions, profound changes have occurred within the structure of American families. This study delves into the intricate dynamics of divisions of household labor (DoL), self-esteem, and relationship satisfaction within the context of contemporary relationships. Drawing on data from the Panel Analysis of Intimate Relationships and Family Dynamics (Pairfam), this study tested five hypotheses, and investigates how perceptions of fairness in DoL tasks influence self-esteem and relationship satisfaction. Significant associations were found between reported share of DoL and indicated fairness of DoL, indicated fairness of DoL and relationship …

Sex Differences In Pediatric Hypertension: Obesity, Stress, And The Renin-Angiotensin System, Allyson Dyar

Theses and Dissertations--Nutrition and Food Systems

Pediatric hypertension, linked to long-term cardiovascular risks, shows increasing prevalence and varying patterns between boys and girls. This study explores sex-based differences in hypertension among 251 children aged 6-18 from Kentucky Children’s Hospital. Using 24-hour ambulatory blood pressure monitoring (ABPM) and assessing plasma renin, aldosterone, and cortisol, we examined blood pressure severity by sex. Girls showed a higher incidence of severe hypertension and elevated cortisol levels, whereas boys had higher mean systolic blood pressure. Aldosterone was associated with night systolic blood pressure in girls, while night diastolic blood pressure was linked to aldosterone in both sexes and renin in girls. …