Medicine and Health Sciences Commons^™

Characterization Of Adiposity And Inflammation Genetic Pleiotropy Underlying Cardiovascular Risk Factors In Hispanics., Mohammad Yaser (Anwar)

Electronic Theses and Dissertations

The observed overlap between genetic variants associated with both adiposity and inflammatory markers suggests that changes in both adiposity and inflammation could be partially mediated by common pathways. The pervasive but sparsely characterized “pleiotropic” genetic variants associated with both adiposity and inflammation have been hypothesized to provide insight into the shared biology. This study explored and characterized the genetic pleiotropy underpinning adiposity and inflammation using genetic and phenotypic observations from the Cameron County Hispanic Cohort (CCHC). A total of 3,313 samples and >9 million single nucleotide polymorphisms (SNPs) were examined in this study. Mixed model genome-wide association studies (GWAS) were …

The Sick Ones., Christian Loriel Lucas

Electronic Theses and Dissertations

This thesis consists of a collection of linked short stories, connected at the intersections of medicine, public health, race, gender, and socioeconomics. The Sick Ones was completed during a time of social unrest and the emergence of the Covid-19 virus. Inspired by medicine’s history of exploiting sick, poor, and racialized bodies, The Sick Ones explores the treatment of illness and societal woes in a near-speculative future. Each story is plot-driven, but complimented by a protagonist who keeps the narrative grounded, as they attempt to survive unprecedented circumstances. Some of the protagonists are complicit in their own medical exploitations, while others …

The Green House Nursing Home Model: The Gh Elements And Their Impact On Quality Of Care In Nursing Homes., Deborah Kaminka Niyongabo

Electronic Theses and Dissertations

Nursing homes (NHs) have been described as hospital-like facilities where residents are more likely to experience isolation or abuse. The Green House (GH) model is a type of culture change which focuses on deinstitutionalizing traditional NHs to provide better quality of care and quality of life to NH residents. The two main objectives of this study are: to describe the GH model and its elements and to identify which GH elements impact the quality of care. This study also seeks to identify organizational theories used in the GH analysis. The next objective is to analyze the impact of the GH …

Development Of A Pediatric Cardiac Assist Maglev Pump For Use With A Universal Driver System., Landon Heath Tompkins

Electronic Theses and Dissertations

Heart failure (HF) remains the leading cause of death, affecting 26 million adults worldwide and 6.5 million adults in the United States. Pediatric HF patients have been a historically underserved population with few options for mechanical circulatory support (MCS) therapy, a leading treatment as an alternative to heart transplantation. To address this clinical need, the Inspired Universal MagLev System is being developed; a low cost, universal magnetically levitated extracorporeal MCS system with interchangeable single-use pumps that will ultimately provide adult and pediatric patients ventricular and respiratory assist therapies. The Inspired Pediatric VAD is the first single-use pump application for this …

Evaluating The Effects Of Pcbs In Non-Alcoholic Fatty Liver Disease & Diabetes And The Role Of Ahr In Regulating The Hepatic Proteome And Lipid Metabolism., Jian Jin

Electronic Theses and Dissertations

Polychlorinated biphenyls (PCBs) are persistent organic pollutants associated with non-alcoholic fatty liver disease (NAFLD) and diabetes. Based on their ability to activate the aryl hydrocarbon receptor (AhR), PCBs are subdivided into two classes: dioxin-like (DL) and non- dioxin-like (NDL) PCBs. This study not only evaluated the chronic effect of DL PCBs (PCB126), NDL PCBs (Aroclor1260 mainly contains NDL), and the DL/NDL PCB mixture (PCB126/Aroclor1260 mixture) on liver, but also explored the acute hepatic effects of DL PCB and potential mechanisms in NAFLD and the role of AhR in regulating hepatic proteome and lipid metabolism, and whether the process independent of …

Predicting Dental Student's Performance On National Board Dental Examination (Nbde) Part I: Exploring Demographic Factors, Dental Admission Test (Dat) Factors, Pre-Program Academic Factors, And Dental Program Academic Performance., Wei-Shao Lin

Electronic Theses and Dissertations

Dental students need to successfully challenge a national licensure examination to be able to practice dentistry. Dental educators currently have difficulty in identifying candidates who are at risk of failing this examination. This non-experimental quantitative study examined existing dental student data from the 2017, 2018, and 2019 graduating classes, using a retrospective and correlational approach to identify possible markers for at risk students. Demographic factors, dental admission test (DAT) factors, pre-program academic factors, dental program academic performance, and National Board Dental Examination (NBDE) Part I performance. A series of independent t-tests and One-Way analysis of variances (ANOVAs) were used to …

Perceptions Of Executive Functions And Self-Care Actions In Major Depressive Disorder., Melanie G. Walters

Electronic Theses and Dissertations

This dissertation encompasses a study of the effect of impaired executive functions on decision-making and self-care of depressive illness. The first chapter provides an introduction and summarizes the body of literature on the executive functions and its association with depressive symptoms. The second chapter contains the second of two systematic reviews which examines conceptualizations of executive functions, classical and current measures used to assess the executive functions, and challenges and limitations related to current methods of assessment. The third chapter describes the development of a vignette technique and its use in a study to examine the association of depressive symptoms …

Plasma Resuscitation Attenuates Intestinal Barrier Disturbance Following Hemorrhagic Shock., Jessica E. Schucht

Electronic Theses and Dissertations

Background: Intestinal ischemia-reperfusion injury (IIRI) following resuscitated hemorrhagic shock (HS/RES) leads to endothelial damage, microcirculatory dysfunction and intestinal barrier breakdown, increasing intestinal permeability. This pathologic process contributes pathophysiology of multiple organ dysfunction syndrome (MODS) in some trauma patients. Although vascular smooth muscle machinery remains intact, microvascular vasoconstriction occurs secondary to endothelial cell damage, resulting in further ischemia and organ injury. Used separately, resuscitation with Fresh Frozen Plasma (FFP) or Direct Peritoneal Resuscitation (DPR) improves the intestinal microcirculation and alleviates organ injury. Further examination of these effects individually or combined could aid in the resuscitation of hemorrhagic shock. Methods: Sprague Dawley …

Tumor-Derived Exosomes Drive Immunosuppressive Macrophages In A Pre-Metastatic Niche Through Nf-Kβ Dependent Glycolytic Metabolic Reprogramming., Samantha M. Morrissey

Electronic Theses and Dissertations

The formation of a pre-metastatic niche is a fundamental requirement for primary tumor metastasis. One of the defining characteristics of a pre-metastatic niche is infiltration of immunosuppressive macrophages. However, how these macrophages acquire their immunosuppressive phenotype remains largely unexplored. Here, we demonstrate that tumor-derived exosomes (TDE) polarize macrophages towards an immunosuppressive phenotype characterized by increased PD-L1 expression through NF-kB-dependent metabolic reprogramming in mice and humans. While NF-κB has previously been shown to act as a direct transcription factor for PD-L1, we report a novel mechanism where TDE-induced NF-κB activation drives PD-L1 expression by augmenting the glycolytic capacity of macrophages through …

Soluble Epoxide Hydrolase Inhibition: A Novel Therapeutic Strategy In Alcoholic Liver Disease., Jeffrey Barr Warner

Electronic Theses and Dissertations

Emerging evidence suggests that soluble epoxide hydrolase (sEH) inhibition is a valuable therapeutic strategy for the treatment of numerous diseases. sEH rapidly degrades cytochrome P450-produced epoxygenated lipids (epoxy-fatty acids, epFAs), which generally exert beneficial effects on several cellular processes. sEH hydrolysis of epoxy-fatty acids produces dihydroxy-fatty acids which are typically less biologically active than their parent epoxide. sEH inhibition has shown efficacy in treating numerous pathologies associated with non-alcoholic liver disease, yet no efforts to date have tested the efficacy of sEH inhibition in alcoholic liver disease (ALD). Herein, we measured the levels of sEH expression and epFAs in human …

Trust In Primary Care Providers: Perspectives From Deaf People., Greir Ander Huck Flynn

Electronic Theses and Dissertations

Trust is an integral part of the patient-provider relationship, responsible for influencing several key aspects of healthcare behaviors and patient perceptions of health outcomes. Though the topic has previously been discussed by scholars, little evidence exists to support the application of our understanding of trust in culturally Deaf populations. As such, this dissertation seeks to lay the necessary groundwork for further investigations on the topic by first understanding the nature of trust in patient-provider relationships from the perspectives of culturally Deaf people. The dissertation is comprised of five chapters. The first chapter provides an introduction to salient terms and concepts …

Modulation Of Inflammatory Pathway By Inflammatory Inhibitor Jsh-23 Mitigates Diabetic Retinopathy., Rubens Petit Homme

Electronic Theses and Dissertations

Diabetic retinopathy (DR) is the most common microvascular complication of diabetes mellitus (DM). Its pathology is consisted of the breakdown of the blood-retinal barrier (BRB), particularly the inner blood-retinal barrier (iBRB). The exact mechanism that leads to the iBRB impairment and the development of DR has not been elucidated yet. However, chronic inflammation that is hallmark of the type I DM has recently become a key focus in DR study. Hyperglycemia causes dysregulation of nuclear factor-kappa B (NF-kB); and its constant activation increases the expression of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and intercellular adhesion molecule-1 (ICAM-1) in the …

Mechanisms Of Chromate-Induced Suppression Of Rad51: A One Environmental Health Approach., Rachel M. Speer

Electronic Theses and Dissertations

Lung cancer is the leading cause of cancer death. Lung cancer is commonly associated with smoking, however, 1 in 5 women and 1 in 12 men who develop lung cancer are never-smokers. Environmental exposures, therefore, account for a significant portion of lung cancer cases. Hexavalent chromium [Cr(VI)] is a global environmental contaminant and known human lung carcinogen. Cr(VI) and other carcinogenic metals induce chromosome instability, an early event in lung cancer. Structural chromosome instability arises in part due to failed DNA repair. Particulate Cr(VI), the most potent form of Cr(VI), induces DNA double strand breaks and inhibits the high-fidelity DNA …

N-Acetyltranserase 2 (Nat2) Genotype Polymorphism In Cryopreserved Human Hepatocytes And Chinese Hamster Ovary (Cho) Cells., Mariam Refaat Zaky Habil

Electronic Theses and Dissertations

Arylamine N-acetyltransferases, NAT1 and NAT2, catalyze the detoxification and/or activation of drugs and aromatic amine carcinogens. Single nucleotide polymorphisms or SNPs result in different human NAT2 genotypes thus dividing the population into rapid, intermediate, and slow acetylators. We hypothesize allelic variants of NAT2 genotype will decrease levels of N-acetylation, cytotoxicity, oxidative stress, DNA adduct formation, and mutagenesis compared to the reference allele NAT2*4. Cryopreserved human hepatocytes expressing different NAT2 genotypes and NER-deficient Chinese hamster ovary (CHO) cells transfected with human CYP1A2 and human NAT2*4, NAT2*5B or NAT2*7B have been used to investigate N-acetylation of different xenobiotics. In …

Moral Distress And Moral Residue Among Nurses Working In The Surgical Intensive Care Unit: A Descriptive Qualitative Approach., Adam Tyler Booth

Electronic Theses and Dissertations

Introduction: Approximately one in five Americans will die in the intensive care unit (ICU). Nurses spend more time with chronically ill and end-of-life patients than any other healthcare professional, and may perceive some actions in the ICU as immoral. Moral distress is defined as knowing the right course of action to take but being hindered by institutional constraints. Development of the Moral Distress Scale-Revised revealed that 31% of ICU nurses left a prior position or considered leaving their current nursing job because of moral distress. The purpose of this descriptive qualitative study is to explore surgical ICU (SICU) nurses’ perceptions …

Tissue-Resident Myeloid-Derived Suppressor Cells Modulate Immune Homeostasis In Healthy Adipose., Katlin Brooke Stivers

Electronic Theses and Dissertations

Our goal with this study was to gain insight into the homeostatic immune cell network in healthy adipose tissue. Specifically, we sought to determine if the immature myeloid cells found in healthy and inflamed adipose were, in fact, tissue-resident myeloid-derived suppressor cells (MDSCs). Using various in vitro and in vivo methods, we have uncovered a population of CD11b^Hi Ly6C^Hi Ly6G^- MDSCs resident in healthy adipose tissue. To the best of our knowledge this is the first time that these cells have been investigated and described in healthy adipose tissue. Systemic MDSC depletion lead to the accumulation of …

Plasmodium Impairs Antibacterial Innate Immunity To Systemic Infections In Part Through Hemozoin-Bound Bioactive Molecules., Christopher Lynn Harding

Electronic Theses and Dissertations

Despite efforts to decrease the global health burden of malaria, infections with Plasmodium species continue to cause over 200 million episodes of malaria each year which resulted in 405,000 deaths in 2018 [1]. One complication of malaria is increased susceptibility to invasive bacterial infections. Plasmodium infections impair host immunity to non-Typhoid Salmonella (NTS) through activities of heme oxygenase I (HO-I) )-induced release of immature granulocytes and myeloid cell-derived IL-10. Yet, it is not known if these mechanisms are specific to NTS. We show here, that Plasmodium yoelii 17XNL (Py) infected mice had impaired clearance of systemic Listeria monocytogenes (Lm) during …

Epithelial Responses To Porphyromonas Gingivalis In The Community Context., Zackary Ray Fitzsimonds

Electronic Theses and Dissertations

Porphyromonas gingivalis, a keystone pathogen for periodontal disease, initiates a complex molecular dialogue with gingival epithelial cells, leading ultimately to disruption of host signaling pathways. Dysbiotic host responses are also thought to contribute to the initiation and progression of oral squamous cell carcinomas. Recently, the homeostatic commensal Streptococcus gordonii has been shown to antagonize P. gingivalis-induced epithelial cell signaling events in host cells, such as proliferation and migration. The aim of this study was to characterize pathways that P. gingivalis targets to disturb host signaling, with a specific focus on pathways that S. gordonii can restore to homeostatic …

Identification And Structural Characterization Functional Motifs In The Porphyromonas Gingivalis Mfa1 Short Fimbria., Mohammad K. Roky

Electronic Theses and Dissertations

Porphyromonas gingivalis is a causative agent of periodontal disease, initially colonizes the oral cavity by adhering to commensal streptococci. Adherence requires the interaction of the minor fimbrial protein (Mfa1) of P. gingivalis with streptococcal antigen I/II (Ag I/II). A peptide derived from Ag I/II peptide has been well characterized and shown to significantly reduce P. gingivalis colonization and bone loss in vivo, suggesting that this interaction represents a potential target for therapeutic intervention. However, the functional motifs of Mfa1 involved in the interaction with Ag I/II remain uncharacterized. A series of N- and C-terminal peptide fragments of Mfa1 were …

Application Of Machine Learning Technologies For Detection Of Proximal Lesions In Intraoral Digital Images: In Vitro Study., Rohit Vadlamani

Electronic Theses and Dissertations

Background: Interpretation of bitewing radiographs is influenced by factors such as acquisition parameters (e.g. exposure, type of sensor), clinical technique, visualization (e.g. monitor type and calibration) and the observer (e.g. experience and fatigue bias). We hypothesized that the use of artificial intelligence (AI) will reduce visualization and observer factor in bitewing interpretation and improve diagnostic accuracy. Objective: The purpose of the present study was to evaluate the use of AI in the form of a machine-learning algorithm to detect and quantify proximal lesions compared with human trained observers. Methods: 16,000 anonymized, digital bitewings of patients were hand searched and non-bitewing, …

Oral Health-Related Quality Of Life In Us Adults With Type 2 Diabetes., Giang Truong Vu

Electronic Theses and Dissertations

This dissertation focused on the relationship between type 2 diabetes (T2DM) and oral health-related quality of life (OHRQoL) and the factors associated with this relationship in the US. The objectives of the dissertation research were a three-part process: (1) to understand the relationships of T2DM with poor OHRQoL, clarify risk and preventive factors that affect this association, and identify research gaps in the literature, (2) to analyze risk factors associated with poor OHRQoL in US adults with T2DM using a nationally representative random probability cluster sample, and (3) to apply structural equation modeling (SEM) to a simplified Andersen’s Behavioral Model …

Mechanistic Insight Of The Role Of Nherf1 In Cisplatin-Induced Acute Kidney Injury., Adrienne M. Bushau-Sprinkle

Electronic Theses and Dissertations

Background. Acute kidney injury (AKI) develops in 30% of patients who receive cisplatin, a widely used chemotherapeutic agent. We previously showed that NHERF1 loss resulted in increased susceptibility to cisplatin nephrotoxicity. The overarching goal of this dissertation was to elucidate mechanisms of susceptibility to cisplatin-induced AKI, specifically the effects of NHERF1 loss on tubule cell metabolism, tubule cell mitochondrial function, and alterations in oxidative state and/or renal handling of cisplatin. Methods. 2-4 month male wild type (WT) and NHERF1 knock out (KO) mice were treated with either vehicle control or cisplatin (20 mg/kg dose IP) for 4, 24, and 72 …

Tobacco Enhances Bacterial-Induced Periodontal Bone Loss In Mice., Mina Iskander

Electronic Theses and Dissertations

Background: Tobacco smoking is the leading environmental risk factor for periodontal diseases. Delineation of the mechanisms underlying tobacco-induced or exacerbated periodontitis is hampered by the lack of an appropriate and reliable animal model. Hypothesis: We hypothesized that Porphyromonas-gingivalis-infected, cigarette smoke-exposed mice would represent reproducible models of acute (ligature model) and chronic (oral gavage model) tobacco-enhanced periodontitis that reflect multiple aspects of the disease noted in human smokers. Methods: In a chronic oral gavage disease model, Balb/c mice (6-8 weeks, 4 groups of n = 6 per group) were exposed to smoke produced by a Teague-10 smoking machine from 1R6F research …

Evaluation Of Tracing Techniques In The Rat Spinal Cord Using A Custom Matlab Application., Rachel M. Zalla

Electronic Theses and Dissertations

The objective of this research project is to evaluate the efficiency of traditional chemical tracing compared to dual-viral tracing for labeling long ascending propriospinal neurons (LAPNs) in the uninjured rat spinal cord, and to develop a MATLAB program which will accurately quantify this labeling.

To evaluate chemical tracing, Fluoro-Ruby (FR) was injected at the level of the axon terminals, and the number of ipsilateral labeled cell bodies at lumbar level was quantified. Similarly, two dual-viral systems were evaluated, by either injecting retro-AAV-Cre or HiRet-Lenti-Cre unilaterally in combination with a Cre-dependent adeno-associated virus. The HiRet-Lenti and FR groups labeled significantly greater …

Converting Threats Into Opportunities Predicting Medical Error Reporting Behavior., Whitney Thomas Rogers

Electronic Theses and Dissertations

Medical errors are a public health epidemic and a major threat to patient safety. Estimates suggest they may be responsible for 210,000 - 440,000 preventable deaths per year. This would make medical errors the third leading cause of death in the United States. The societal burden of medical errors is steep, with the economic impact near $1 trillion. The purpose of this study was to use a theory-driven approach to better understand the reporting behavior of healthcare professional. Increased error reporting leads to heightened awareness of the precursors or conditions generating errors, which can then be corrected. In its most …

A Novel Approach To Hiv Prevention: Understanding Multi-Level Influences On Hiv Pre-Exposure Prophylaxis (Prep) Uptake And Outreach Among African Americans., Suur Debrah Ayangeakaa

Electronic Theses and Dissertations

This dissertation examined and provided basis for addressing factors related to HIV pre-exposure prophylaxis (PrEP) engagement, outreach, and uptake among high-risk African American youth groups in Louisville, KY. This qualitative dissertation study was designed through the lens of an interpretive framework of social constructivism which holds that multiple realities and interpretations exist and are socially constructed through the lived experiences of individuals and their interactions with others. Thus, lived experiences of various African American youth groups in Louisville as well as key informants of AIDS service organizations (ASOs) across the U.S. (including Louisville) were explored to develop a deeper understanding …

The Role Of Inter-Enlargement Propriospinal Neurons In Locomotion Following Spinal Cord Injury., Courtney Therese Shepard

Electronic Theses and Dissertations

The focus of this dissertation is to explore the functional role of two anatomically-defined pathways in the adult rat spinal cord before and after spinal cord injury (SCI). To do this, a Tet^On dual virus system was used to selectively and reversibly silence neurons with cell bodies at spinal segment L2 and projections to spinal segment C6 (long ascending propriospinal neurons, LAPNs) and neurons that originate in the C6 spinal segment and terminate at L2 spinal segment (long descending propriospinal neurons, LDPNs). This dissertation is divided into five chapters. Chapter One provides background information regarding spinal cord injury, locomotion, …

Dual Role Of Antimicrobial Peptide Cathelicidin In Alcohol-Associated Liver Disease., Fengyuan Li

Electronic Theses and Dissertations

Patients with alcohol-associated liver disease (ALD) have high morbidity and mortality in its severe forms. One of the major features in different forms of ALD is the altered gut microbiota. Antimicrobial peptides (AMPs) play a crucial role in maintaining gut microbiota homeostasis. LL-37 (known as CRAMP in mouse) is the sole member of the human cathelicidin family and has piqued great research interest for its dual role in modulating microbiota and the immune response in metabolic diseases. Inflammasome activation is an important component of the liver pathophysiology in ALD and requires two signals for its full activation to induce the …

The Emerging Oral Pathogen, Filifactor Alocis, Disrupts Neutrophil Functions To Enhance Survival And Dysregulate Inflammation., Irina Miralda Molina

Electronic Theses and Dissertations

Periodontitis is an irreversible, chronic inflammatory disease where pathogenic microbial communities accumulate in the gingival crevice. Advances in culture-independent techniques have facilitated the identification of new bacterial species in periodontal lesions, such as the Gram-positive anaerobe, Filifactor alocis. Neutrophils are a major component of the innate host response, and the outcome of their interaction with F. alocis may be a determinant of oral health status. While neutrophil functions typically protect the host against periodontal disease, oral pathogens have adapted to evade or disarm neutrophil microbicidal functions while promoting mechanisms that drive inflammation, which also provides a source of nutrients …

Tobacco Smoke Exposures And Fertility-Related Outcomes Among Females Seeking Fertility Care, And The Interaction With N-Acetyltransferase 2 (Nat2).., T'Shura S. A. Ali

Electronic Theses and Dissertations

Cigarette smoke contains thousands of harmful substances and is one of the leading preventable causes of mortality and morbidity in the United States. Past studies examining tobacco smoke exposures on fecundability and pregnancy outcomes are inconsistent. NAT2 is an important enzyme in the metabolism of xenobiotic substances found within tobacco smoke. This preconception cohort study examines associations between active smoking and secondhand smoke exposure (SHSe) on fecundability and spontaneous abortion (SA), and explores a possible interaction with NAT2 acetylator status. A total of 223 women seeking fertility care were followed for up to 2.3 years. Preconception tobacco smoke exposures were …