Medicine and Health Sciences Commons^™

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 …

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 …

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 …

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 …

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 …

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 …

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 …

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 …

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 …

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 …

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 …

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, …

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 …

Preventable Hospitalization Among Type 2 Diabetes Patients In Kentucky Before And After Medicaid Expansion 2010-2017., Turky Jamil Arbaein

Electronic Theses and Dissertations

Objectives: 1) Analyze county level variation in T2DM-PH rates in Kentucky before ACA (2010-2013) and after the ACA (2014-2017). 2) Analyze the relationship between county level socioeconomic factors (income per capita, percentage of uninsured people, percent of urban population, primary care and general preventive offices, population aged 65 and above, median age, household income, percentage in poverty, and unemployment rate ) and county level T2DM-PH rates before (2010-2013) and after (2014-2017) ACA implementation in Kentucky. Method: This research was conducted in two phases: Phase one of this study estimated the county-level PH variation among T2DM patients across eight years (2010-2017), …

Volatile Organic Compound Exposure And Cardiometabolic Syndrome Risk In A Nationally Representative Cohort., Stacey Lane Konkle

Electronic Theses and Dissertations

BACKGROUND: The relative importance of environmental exposures such as volatile organic compounds (VOCs) is one of the paramount public health priorities of our time, yet is presently unstudied. VOCs are ubiquitous in the environment and have been associated with numerous adverse health effects, including a number of cardiovascular and metabolic effects that are components of Cardiometabolic Syndrome (CMS). OBJECTIVES: To examine the relationship between CMS and individual-level exposures to VOCs, measured as urinary metabolites of VOCs (UM-VOCs), in a nationally representative sample. METHODS: Associations between urinary biomarkers of exposure to 19 parent VOCs and CMS were assessed using the National …

Tobacco-Derived Aldehydes: Platelet Activation, Thrombosis, And The Role Of Trpa1., Andre Dwayne Richardson

Electronic Theses and Dissertations

Cigarette smoking is the single largest risk factor for cardiovascular disease (CVD) pathophysiology. Numerous researchers have shown potential associations between aldehydes in tobacco-derived aerosols from mainstream cigarette smoke (MCS) or electronic cigarettes (e-cigs) and their cardiotoxicity by damaging blood vessel endothelium. The severity of exposure to these toxicants can furthermore lead to adverse cardiovascular outcomes such as myocardial infarctions, stroke, coronary and peripheral artery disease, or atherosclerosis due to blood clots, a pro-thrombotic event. However, the mechanisms by which levels of harmful and potentially harmful constituents (HPHCs) such as aldehydes induce thrombosis are not well-known. Of specific interest, evidence has …

Functionalizing Nanoparticles With Cafa Protein To Target Bar Peptide For Oral Delivery Applications., Hetal Desai

Electronic Theses and Dissertations

Background: Porphyromonas gingivalis adherence to Streptococcus gordonii may be important for P. gingivalis colonization in the oral cavity. Nanoparticles encapsulating synthetic peptide BAR (BAR-NPs) inhibit P. gingivalis adherence more potently than free BAR. However, BAR-NPs would exhibit low retention in an open flow environment. Hypothesis: Targeting BAR-NPs to the streptococcal surface using CafA protein will enhance their efficacy. Methods: CafA-modified NPs encapsulating BAR were synthesized using double emulsion approach. Surface binding and retention, and release kinetics of BAR from CafA-modified NPs was assessed. Functional inhibition assays were performed using dual a species biofilm. Results: CafA-modified NPs demonstrated specificity of adhesion, …

Development Of Rationally Designed Live Attenuated Vaccines For Lassa Fever And Venezuelan Equine Encephalitis., Dylan Macgregor Johnson

Electronic Theses and Dissertations

Lassa Virus (LASV) and Venezuelan Equine Encephalitis Virus (VEEV) are two single stranded RNA viruses belonging to the Arenavirus and Alphavirus families, respectively. Both are emerging pathogens without approved vaccines or treatments. VEEV is an important biothreat pathogen because it has been weaponized and is extremely infectious as an aerosol. VEEV causes biphasic febrile illness that can progress to a viral encephalitis with low mortality, but high morbidity. LASV causes a viral hemorrhagic fever, Lassa Fever (LF), which is endemic in West Africa, and responsible for between 100-500k annual infections with a 1-2% overall mortality rate. ML29 and VEEV TC-83 …

Tobacco Product-Derived Aldehydes: Effects On Circulating Angiogenic Cells & Implications For Cardiovascular Disease., Jordan B. Lynch

Electronic Theses and Dissertations

Cardiovascular disease (CVD) is the leading cause of death worldwide. Tobacco smoke is the most significant modifiable risk factor in CVD development and contains numerous toxic compounds, including aldehydes, which have been linked to CVD. Formaldehyde, acetaldehyde, acrolein, and crotonaldehyde have been identified as significant contributors to cigarette-induced health effects, but the mechanism of these effects is not well understood. These aldehydes are also found in aerosols produced by e-cigarettes (e-cigs). The goal of this dissertation was to explore the systemic, hematological, and endothelium-related effects of exposure to tobacco products and constituent aldehydes and to identify potential mechanisms of injury. …

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 …

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 …

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 …