Medicine and Health Sciences Commons^™

Investigating The Effects Of Subchronic Dietary Zinc Supplementation On Diet-Induced Metabolic Dysfunction-Associated Steatotic Liver Disease., Oluwanifemi Esther Bolatimi

Electronic Theses and Dissertations

Zinc deficiency is associated with metabolic dysfunction-associated steatotic liver disease (MASLD). Previous studies show zinc supplementation improves steatosis, but its therapeutic effects in established MASLD remain unclear. We developed a model to characterize the effects of zinc supplementation on high-fat diet (HFD) induced MASLD and hypothesized established MASLD would be attenuated. Mice were fed control diet or HFD for 12 weeks and then grouped into normal or zinc-supplemented diets for 8 additional weeks. At euthanasia, plasma and liver tissues were collected for phenotypic analysis. Twelve weeks of HFD altered glucose clearance and body composition. Eight weeks of subsequent zinc supplementation …

Genetic Risk Scores For Hypertension And Chronic Kidney Disease In African Americans., Aastha Kakar

Electronic Theses and Dissertations

Hypertension (HT) and chronic kidney diseases (CKD) are complex conditions, disproportionally prevalent among African Americans (AA) and are influenced by multiple genetic as well as environmental factors. Genetic risk scores (GRS) enable the analysis of the combined effects of multiple single nucleotide polymorphisms (SNPs). This study investigates the association of blood pressure (BP) and CKD GRS with BP, hypertension (HT) and CKD; early-onset HT and CKD; and investigates interactions of the GRSs with environmental measures in AA. We observed a significant association between the BP-GRS with HT, SBP and DBP. The odds of HT for one standard deviation (s.d.) increase …

Ethanol Dysregulates Sirt1-Mediated Lipogenic Signaling Pathways Through Α4*-Nicotinic Acetylcholine Receptors In Hepatocytes., Caitlin Christina Wilkerson

Electronic Theses and Dissertations

Alcohol-associated liver disease (ALD) is a broad spectrum of diseases ranging from steatosis to severe hepatic cirrhosis, none of which have any FDA approved therapies. Downregulation of hepatic Sirtuin 1 (Sirt1) activity by ethanol has been shown to lead to an upregulation of the pro-lipogenic gene targets under its jurisdiction, resulting in increased lipogenesis and triglyceride accumulation. It was hypothesized that ethanol acts on α4*-nicotinic acetylcholine receptors (α4*-nAChRs) in hepatocytes to decrease Sirt1 expression, which ultimately dysregulates lipid metabolic homeostasis. Ethanol’s effects were investigated in cultured AML12 hepatocytes and in WT primary mouse hepatocytes acutely exposed to ethanol. Consistent with …

Environmental Exposures And Aging., Daniel Chris Gomes

Electronic Theses and Dissertations

In recent years, research into air pollution has shown that exposure to certain components in air pollution, primarily PM2.5 can accelerate biological aging and thereby lead to increased susceptibility to multiple diseases. We hypothesize that prolonged exposure to air pollutants can result in premature aging leading to extensive tissue dysfunction and susceptibility to diseases. To examine this, we exposed mice to PM2.5 for 9, 15, and 21 days, then measured the telomere lengths, cellular senescence, and histone methylation patterns of multiple cell types. We found consistently increased telomere attrition, cellular senescence and advanced age-consistent histone methylation patterns in groups exposed …

Genetically Engineering Gingipains For High Yield Large Scale Purification., Andrew E. Fuchs

Electronic Theses and Dissertations

Porphyromonas gingivalis is a keystone oral pathogen in the progression of periodontal disease and has been implicated in the etiology of many other systemic human diseases. P. gingivalis produces primary virulence factors termed the gingipains, a group of cysteine proteases. There is a high demand for high purity gingipains for downstream in vitro studies where P.g. is implicated, both oral and systemic. Gingipain production candidate mutant P.g. strains were generated to isolate each gingipain for large scale purification and the purified gingipains characterized. Two mutants were determined not to be viable for large scale purification of gingipains, each for different …

Formalizing The Faustian Bargain Within The Healthcare Domain: An End-Of-Life Approach., Rachel Appel

Electronic Theses and Dissertations

A Faustian Bargain refers to an individual making a “deal with the devil,” exchanging something moral or sacred for an unattainable earthly good. The Faustian Bargain has been used to describe a ubiquitous social dilemma inherent to human civilization: exchanging individual liberty for public goods (e.g., security) provided by societal leaders and governments (Ostrom, 1980). Research on Faustian Bargains often examines tradeoffs between outcome utility (i.e., value derived from the outcomes of a decision) and procedural utility (i.e., value derived from being involved in the decision process (e.g., Frey et al., 2004). Much of the research on Faustian Bargains has …

Organizational Change In Saudi Healthcare Settings: Evaluating Organizational And Individual Readiness For Change, And The Mediating Role Of Readiness For Change Between Management Support And Commitment To Change., Sultan Alsaif

Electronic Theses and Dissertations

BACKGROUND: To respond to the constantly changing environment and developments of healthcare, leaders of healthcare organizations have been trying to introduce and implement transformations that allow their organizations to be able to operate effectively and efficiently to meet the shifts in healthcare demand and to deal with new patterns of health issues, comply with the new policies, and to enhance their present in the market. Thus, it is important for managers to determine the level of readiness for implementing organizational changes from to perspectives. These perspectives include organizational readiness for change and individual readiness for change. METHOD: This first manuscript …

Investigation Of Heterocyclic Amines And N-Acetyltransferase 2 Genetic Polymorphism In The Dysregulation Of Hepatic Energy Homeostasis: A Gene-Environment Approach., Kennedy M Walls

Electronic Theses and Dissertations

Heterocyclic amines (HCAs) are mutagens generated when cooking meat for prolonged periods of time or until well-done. Recent epidemiological studies reported significant associations between dietary HCA exposure and insulin resistance and type II diabetes. However, no previous studies have examined if HCAs, independent of meat consumption, contributes to pathogenesis of insulin resistance or metabolic disease. It is well known that HCAs require hepatic bioactivation by cytochrome P450 1A2 (CYP1A2) and N-acetyltransferase 2 (NAT2). NAT2 expresses a well-defined genetic polymorphism in humans that, depending on the combination of NAT2 alleles, correlate to rapid, intermediate, or slow acetylator phenotypes that exhibit differential …

Kdm5b As A Potential Epigenetic Regulator Of Cardiomyocyte Regeneration And Cell Cycle Activation., Dana Hammouri

Electronic Theses and Dissertations

The limited regenerative capacity of adult cardiomyocytes (CMs) is manifested in prevalent morbidity and mortality associated with ischemic heart disease. We previously demonstrated that a combination of four cell cycle factors (4F) promotes efficient cell division in differentiated CMs. The temporal transcriptional reprogramming in the 4F-transduced CMs indicates that epigenetic modifications mediate the cell cycle progression. Through small molecule screening, we evaluated the epigenetic impact on CM’s response in the 4F-transduced CMs. We identified the histone demethylase 5B (KDM5B), which through in vitro and ex vivo genetic knockdown and overexpression studies, exhibited a modulative effect on CM’s cell cycle plasticity …

Food Insecurity And Residential Segregation Among Adults In The United States: The National Health And Nutrition Examination Survey 2017- March 2020 Pre-Pandemic Data., Chandre' L. Chaney

Electronic Theses and Dissertations

Food insecurity is when a household has insufficient food supply due to limited economic resources. It is a public health issue that continues to persist. The health, social, and economic impact affects millions of people nationwide. Residential segregation is a primary cause of inequities and health disparities. It shapes the differences in socio-economic conditions between Blacks and Whites living in the U.S. This country is segregated across racial lines in many of our most populated metropolitan cities. Americans worship in different churches, learn in disparate schools, and live in separate neighborhoods. Residential segregation has consequences that impact the economy, professional …

Investigation Of Possible Inflammatory Response After Ultrasound And Microbubble Procedure In The Spinal Cord., Jenna Wilkerson

Electronic Theses and Dissertations

The purpose of this experiment is to explore the inflammatory effects of focused ultrasound paired with intravenously delivered microbubbles when used in the lumbar spinal cord. There are currently very few pharmaceuticals that can successfully enter the blood spinal cord barrier (BSCB). This technique used at the lumbar enlargement might allow targeted treatment of pathologies involving the spinal cord.

To test the possible inflammatory response of this technique, an animal experiment was performed. 15 animals were given a T12 laminectomy and allowed to fully recover. Once recovered, all animals received FUS+MB at L2 and were euthanized in groups of five …

Clinical And Environmental Factors Affecting The Survival Outcomes Among Stage 1a Tn0m0 First Primary Non-Small Cell Lung Carcinoma Patients In The United States., Naiya Patel

Electronic Theses and Dissertations

Background: Lung cancer is the second leading cause of death in the United States (U.S.). The most prevalent histological type of lung cancer is Non-Small Cell Lung Cancer (NSCLC), which has an overall five years survival of 5% if left untreated. Therefore, early treatment of NSCLC is vital to improve overall survival (OS) outcomes. Several factors affect survival outcomes, which can be categorized as modifiable or non-modifiable. The difference in timely receipt of guideline-concordant treatment affects the survival outcomes of patients with stage 1A NSCLC. This dissertation explored factors that affect treatment and survival outcomes among stage 1A NSCLC patients …

Injury Induced Neuroplasticity And Cell Specific Targeting Of The Lumbar Enlargement For Gene Therapy., Brandon Lee Brown

Electronic Theses and Dissertations

This dissertation is an examination of spinal cord injury induced neuroplasticity and tests whether noninvasive gene therapy can successfully target neurons in the lumbar spinal cord. It begins with an overview of neural control of locomotion and a brief summary of therapeutics that are used and/or in development for treating spinal anatomically characterize s subset of neurons in the spinal cord, long ascending propriospinal neurons, that are involved in interlimb coordination. Characterization of these neurons allows for subsequent evaluation of their potential involvement in injury induced neuroplasticity. This dissertation is divided into five chapters, covering spinal cord injury and therapeutics. …

Swallow, Breathing And Survival: Sex-Specific Effects Of Opioids., Michael Frazure

Electronic Theses and Dissertations

This dissertation presents a series of studies examining mechanisms of deglutition and respiration, and how these vital processes are impacted by opioids. The experiments in Chapter Two investigated the role of the upper esophagus in airway protection through systematic activation of pharyngeal and esophageal mechanoreceptors in a cat electromyography model. Chapter Three compared effects of opioid administration on breathing and swallowing between male and female rats, and found that females are more susceptible to opioid-induced depression of breathing and swallow than males. Findings from Chapters Two and Three led to the development of a translational model of opioid-induced dysphagia using …

Aurka Inhibition-Based Combination Therapy Approaches In Glioblastoma., Muge Sak

Electronic Theses and Dissertations

Glioblastoma is the most common and aggressive central nervous system tumor in adults with a 6% survival rate. Decades of research for improving life expectancy and quality of life have been ineffective. The discovery of better treatment strategies is urgent to improve the survival rates for glioblastoma patients. Aurora Kinase A is a regulator of tumor progression and is overexpressed in glioblastoma. We used a specific Aurora Kinase A inhibitor alisertib in combination with DNA-damaging platinum agent carboplatin or brain-penetrating taxane TPI 287. We investigated the efficacy of these combinations in treating in vitro and in vivo tissue culture models …

Novel Insights Into Oligodendrocyte Biology From Developmental Myelination Studies In Autophagy Deficient Mice And Analysis Of Oligodendrocyte Translatome Response To Contusive Spinal Cord Injury., Michael David Forston

Electronic Theses and Dissertations

Loss of myelin causes severe neurological disorders and functional deficits in white matter injuries (WMI) such as traumatic spinal cord injury (SCI). This dissertation is focused on autophagy in OL development and the OL translatome after SCI. Chapter I describes the history of myelin, OL development, and their involvement in neurodegenerative diseases and SCI. The proteostasis network, in particular autophagy, and its contributions to white matter pathology is discussed. It concludes examining advantages and disadvantages of unbiased omics tools, like RiboTag, to study transcriptional/translational landscapes after SCI. Chapter II focuses on autophagy in OPC/OL differentiation, survival, and proper myelination in …

Incidence And Determinants Of Hypertensive Disorders Of Pregnancy In The Us: Hospitalization Discharge Rate For Preeclampsia, Eclampsia, And Gestational Hypertensions, 2016-2018., Kahir S. Jawad

Electronic Theses and Dissertations

Background: Hypertension remains one of the most prevalent medical issues in pregnancy. It contributes considerably to maternal and fetal morbidity and mortality, making it one of the most significant public health problems. Although various epidemiological studies have been conducted over the past decades to assess the disease incidence and key risk factors associated with hypertensive disorders of pregnancy, current incidence rates and trends are lacking. This is a novel and significant study because there are no current population-based incidence estimates of hypertensive disorders of pregnancy and their subtypes and very few studies with the power to explore a wide range …

The Role Of E-Liquid Constituents In E-Cigarette-Induced Cardiac Arrhythmia And Autonomic Imbalance., Cory Kucera

Electronic Theses and Dissertations

Introduction. Accumulating evidence indicates that exposure to electronic cigarettes (e-cigs) promotes sympathetic dominance and electrophysiologic instability in the heart, potentially culminating in arrhythmogenesis. E-liquids contain various formulations of nicotine and flavorings, but the effects of specific e-liquid constituents and their concentrations on e-cig-induced autonomic imbalance and electrical dysfunction are unresolved. To that end, we tested the hypothesis that e-cigs modify cardiac autonomic balance and ventricular arrhythmogenesis in mice dependent on e-liquid constituent type and concentration. Methods. Using a crossover design and a serial exposure regimen, ECG-telemetered male C57BL/6J mice underwent whole-body exposure to e-cig aerosols generated from e-liquids containing different …

Irreversible Electroporation Potentiates Beta Glucan Induced Trained Innate Immunity: A Novel Combination Treatment For Pancreatic Adenocarcinoma., Matthew Woeste

Electronic Theses and Dissertations

Pancreatic cancer (PC) is a challenging diagnosis yet to benefit from advances in immune oncologic treatments. Irreversible electroporation, a non-thermal method of tumor ablation, is used in treatment of select patients with locally advanced unresectable PC and has potentiated the effect of certain immunotherapies. Yeast-derived particulate β-glucan induces trained innate immunity and successfully reduces murine PC tumor burden. This study tests the hypothesis that IRE may augment β-glucan-induced trained immunity in the treatment of PC. β-Glucan-trained pancreatic myeloid cells were evaluated ex vivo for trained responses and anti-tumor function after exposure to ablated and un-ablated tumor conditioned media. β-Glucan and …

Postpartum Depression In Jamaica: Exploring The Lived Experiences., Shakeyrah Elmore

Electronic Theses and Dissertations

The purpose of this study was to explore the lived experiences of Jamaican women with postpartum depression (PPD). It is estimated globally, postpartum depression impacts 10-20% of women. In Jamaica, rates exceed global averages, with 26-60% of women experiencing PPD. Untreated maternal depression poses a significant physical, social, and economic threat to Jamaican women, children, and society as a whole. This study affirms that maternal mental health and postpartum depression are global public health concerns. There are limited studies that have examined PPD in Jamaican women, especially qualitatively. This research study utilized a qualitative descriptive approach to examine PPD experiences …

The Impact Of Kentucky’S Medicaid Expansion On Adult Coverage And Diagnosis Of Type 2 Diabetes Mellitus And Diabetic Peripheral Neuropathy, The Use Of Antihyperglycemics And The Role Of Social Determinants Of Health 2011-2018., Brian Mcroberts

Electronic Theses and Dissertations

Objectives: This study analyzed the impact of Medicaid expansion in Kentucky on coverage of adults aged 19-64 and the diagnosis of type 2 diabetes mellitus (T2DM) and diabetic peripheral neuropathy (DPN) and the use of antidiabetic medications or insulin (antihyperglycemics) for T2DM, controlling for Social Determinants of Health (SDOH). Method: This study assembled ICD-based claims and prescription drug NDC claims from all adult residents of Kentucky enrolled in Medicaid from 2011 to 2018. Three-digit zip code (Zip-3) data was appended to each case from the American Community Survey to provide SDOH variables. Tests performed included ANOVA, decision trees, varimax rotated …

An Analysis Of The Effects Of Certified Electronic Health Records On Organizations And Patients., Picandra Elzie

Electronic Theses and Dissertations

The growing technological advancement of electronic health records can become an issue with quality and electronic patient information exchange if hospitals do not adhere to federal guidelines. It is recommended that hospitals utilize certified electronic health records (EHRs) to receive financial incentives. This certification is supposedly also associated with the quality of the EHR itself. The certification process is criticized for allowing EHR vendors to meet a set of limited functions known in advance. EHRs can affect healthcare quality and electronic health information exchange. This dissertation explored what is known about the effects of certified EHRs on length of stay …

Supraspinal Reorganization After Pediatric-Onset Spinal Cord Injury., Luis Alvarado

Electronic Theses and Dissertations

Pediatric spinal cord injury (SCI) disrupts the efferent and afferent flow of the developing brain, leading to devastating functional impairments below the injury site, yet our understanding of its impact on the brain remains limited. This study examines supraspinal reorganization in children with SCI using electrophysiology and neuroimaging techniques to understand the relationship between residual spinal transmission and supraspinal reorganization. Chapter 2 discusses the development of a child-centric approach using ‘learn, play, and practice’ to foster a trusting relationship with each child and increase compliance with experimental protocols. Chapter 3 evaluates the residual neural transmission of three spinal pathways in …

An Evaluation Of Hospital-Based Health Technology Assessment Processes In The United States., Scott Skinner

Electronic Theses and Dissertations

This research study explored the practices of hospital-based health technology assessment (HTA) in the U.S., as experienced by healthcare technology management (HTM) professionals. HTA can play an important role in helping to evaluate health technologies at both the macro (e.g., policy) level as well as at the micro (e.g., institutional) level of the public health ecosystem (C. S. Goodman, 2004). HTA seeks to broadly evaluate the effects, properties, and other impacts of various health technologies (C. S. Goodman, 2004). Common goals of HTA are to evaluate the safety, effectiveness, and cost-benefit of health technologies. A primarily phenomenological approach was used …

Toward A Comprehensive Account Of Orientation Selectivity In The Retina., Megan Zipperer

Electronic Theses and Dissertations

Retinal Ganglion Cells (RGCs) form functionally distinct signaling channels that selectively encode features of the visual input including direction of motion, contrast polarity, size, and color. A highly conserved visual channel amongst vertebrates conveys orientation selectivity, i.e., the selective firing of neuronal cells in response to elongated stimuli along a preferred orientation. Orientation selectivity is an apparent critical computation and several studies have reported aspects of it, including cell type identity in anatomical reconstructions, and functional characterization of at least four different identified RGC types. But how cell types in the different studies relate is not well resolved; the mechanisms …

Factors Associated With Skin Cancer Prevention: Primary And Secondary Behaviors., Jeanne Ward

Electronic Theses and Dissertations

Skin cancer, seemingly more innocuous than other cancers, maintains the highest incidence among cancers in the United States. While it is treatable early, metastasized melanoma or other carcinomas present severe illness with high mortality rates and disproportionate 5-year survival rates among ethnic/racial groups. Fortunately, most skin cancer is highly treatable when found in the early stages. However, this necessitates prevention tactics to avoid the causative agent, ultraviolet radiation, and regular skin screening to catch the disease in earlier stages. Unfortunately, these tactics are not widely conducted by adults, despite substantial skin cancer awareness. Therefore, motivating people to perform these health …

Barriers And Facilitators Of Dairy Consumption Among Individuals With Metabolic Syndrome., Kofi Amoh-Mensah

Electronic Theses and Dissertations

About 35% of the United States adult population meets the criteria for metabolic syndrome, representing about 85 million individuals. Consuming dairy products protects against the development of the metabolic syndrome and protects against the development of complications associated with it. However, approximately 10% of the U.S. population meets the daily recommendation for dairy products. Information about the use of dairy products among people living with metabolic syndrome is relatively unknown, even though it will benefit them the most. About 49% of respondents met the guidance of three servings per day, and the most common facilitator was access to dairy products.

Adverse Birth Outcomes: Investigating The Role Of Nativity And Perceived Racial Discrimination Among Black Mothers Enrolled In Des Moines, Iowa Healthy Start., Kendria Kelly-Taylor

Electronic Theses and Dissertations

Birth outcomes for Black women in the United States (US) are disproportionately worse in comparison to non-Black women, even when controlling for potential confounders. Existing studies suggest foreign-born (FB) Black women present better birth outcomes in comparison to US-born (USB) Black women. Also, the longer FB Black women live in the US, the more their perinatal health advantage diminishes. Racial discrimination has been hypothesized as a potential reason for this decline. This dissertation investigates the relationship between nativity and adverse birth outcomes while also exploring how the reporting of racial discrimination impacts birth outcomes among FB and USB Black mothers …

Our Story, Our Song: Assessing And Addressing Black Women's Healthcare Experiences., Jason Deakings

Electronic Theses and Dissertations

Despite advancements in medicine and health sciences, health disparities and declining life expectancy persists among Black women in the United States. Researchers and non-traditional healthcare providers suggest alternative healing (e.g., music and Sister Circles) and research methodologies to achieve a culturally conscious, traumainformed, quality, and holistic care and practice. The intersecting identities and cultural responsibility of Black women highly influences the barriers and facilitators on the uptake of healthcare services. Utilizing a community engaged research approach, this qualitative study assessed the healthcare experiences, as well as the role of music in the lived and retold experiences of Black women navigating …

The Association Of Long Working Hours And The Use Of Prescription Sedatives Among U.S. Workers., Emmanuel Ezekekwu

Electronic Theses and Dissertations

BACKGROUND: Meeting the needs of a round-the-clock and globalized society has led to an increase in long working hours. This trend has been accompanied by a corresponding rise in sleep disorders and subsequent use of sedating medications. Overtime hours have been associated with adverse health outcomes such as cardiovascular diseases, symptoms of psychological distress, and health behaviors, including risky intake of alcohol and smoking. Hence, the main objectives of this three-paper dissertation were to examine the multi-faceted relationship between working hours, the use of prescription sleep aids, the onset of psychological distress, and the use of health care services. METHODS: …