Diseases Commons^™

Evaluating The Feasibility And Preliminary Effectiveness Of A Tailored Diabetes Education Program For Rural Residents, Brittany L. Smalls, Oluwatosin Leshi, Suraksha Khanal, Grejika E. Abram-Erby

Journal of Appalachian Health

Introduction: Diabetes is a top ten Rural Healthy People 2030 priority for health improvement among rural Americans. Socioeconomic, environmental, geographic and political barriers contribute to the type 2 diabetes (T2D) prevalence and its disparate impact in rural communities. However, promoting proper self-care behaviors via self-management education can help people with diabetes better manage their condition.

Purpose: To account for the social environmental factors that affect rural residents, a tailored diabetes education program was developed, and the program’s effectiveness in improving diabetes knowledge and T2D-related health outcomes was assessed.

Methods: Using data collected from Appalachian Kentucky residents enrolled in a six-week, …

Infective Endocarditis Hospitalizations In Kentucky, 2008-2018: Spatial And Temporal Trends, Meera Marji, Steve Browning, W. Jay Christian, Richard Charnigo, Steve W. Leung, Anna Kucharska-Newton

Journal of Appalachian Health

Introduction: Infective endocarditis (IE) hospitalization rates have increased significantly in the last decade, primarily due to the opioid epidemic. In 2016, Kentucky (KY) ranked among the top ten states for opioid-related overdose deaths, but limited data exist on IE trends in KY.

Purpose: This study seeks to examine county-level spatial and temporal trends in IE hospitalization rates in KY.

Methods: Hospital inpatient discharge data from 2008–2018 for KY residents aged 18 and older were analyzed. IE admissions and drug use status were identified using ICD-9 & 10 diagnosis codes. U.S. Census data calculated yearly IE hospitalization rates per 100,000 residents. …

Renin-Angiotensin-Aldosterone System In Preeclampsia: Pathophysiological Insights And Links To Vascular Dementia, Robin C. Finch, Jenny Lutshumba, Elizabeth Mirsky, Esther Ndashaala, Kelsey Bullens, Emma Smith

Pediatrics Faculty Publications

Pre-eclampsia, a condition characterized by new-onset hypertension during pregnancy and one or more indices of organ damage, is a major driver of both short and long-term maternal health outcomes. Individuals with a history of pre-eclampsia are at increased risk for cardiovascular, renal, and other chronic diseases. Recent studies have linked pre-eclampsia history with increased risk of dementia later in life, underscoring the importance of new guidelines emphasizing blood pressure control to reduce the risk of cognitive decline. Unfortunately, neither mechanisms underlying causes of pre-eclampsia nor their links with cognitive function are well understood. Vascular contributions to cognitive impairment and dementia …

Nutrient-Driven Transcription Factor-Dna Interactions And Their Signaling Mechanisms In Metabolic Disease, Evelyn A. Bates

Theses and Dissertations--Nutritional Sciences

Metabolic homeostasis is maintained through tightly coordinated signaling networks that integrate diverse physiological inputs. Central to this regulation are transcription factors, which sense nutrient, hormonal, and vitamin-derived signals and translate them into coordinated gene expression programs. Transcription factor activity is governed by DNA binding, recruitment of coregulatory proteins, and interactions with specific response elements in gene promoters, which allows them to selectively modulate diverse metabolic pathways. Owing to their multifactorial and tunable nature, transcription factors have emerged as promising targets for the treatment and diagnosis of metabolic diseases, including metabolic dysfunction-associated steatotic liver disease (MASLD). This dissertation explores the molecular …

Biomechanical Effects Of Exercise-Based Interventions In Chronic Nonspecific Low Back Pain: A Systematic Review And Meta-Analysis, Lara De Vecchi Machado

Theses and Dissertations--Kinesiology and Health Promotion

Chronic nonspecific low back pain (CNLBP) is the leading cause of years lived with disability worldwide and represents a complex, multifactorial, and heterogeneous condition. It is characterized by substantial interindividual variability in muscle activation patterns, lumbo-pelvic coordination, and movement strategies. Although exercise is widely recommended as a first-line intervention and its clinical benefits are well established, the biomechanical mechanisms underlying functional improvement remain fragmented in the literature and are rarely synthesized quantitatively.

This dissertation conducted a systematic review with meta-analysis to investigate the biomechanical effects of exercise-based interventions in individuals with CNLBP. A total of 39 studies were included and …

Metabolism As A Regulator Of Sleep And Cortical Activity In Health And Alzheimer’S Disease, Nicholas J. Constantino

Theses and Dissertations--Neuroscience

Metabolic flexibility is essential for maintaining normal physiological function, enabling an organism to sense, flux, utilize, and switch fuel sources in response to changing energetic availability, demand, and cellular needs. Energetic demands are state-dependent, with wake and sleep exhibiting distinct metabolic profiles. Sleep is highly sensitive to changes in metabolism and requires metabolic flexibility to both transition into and maintain sleep stability. Alzheimer’s disease (AD) is increasingly recognized as a disease of altered metabolism yet is often framed as a disease of energetic failure. We instead define AD as a disease of metabolic inflexibility, characterized not by insufficient energy availability, …

Environmental Predictors Of Human Lyme Disease Incidence Across Appalachian Counties In Kentucky, Virginia, And West Virginia, 2000-2019, Karlie D. Rennison

Theses and Dissertations--Epidemiology and Biostatistics

This ecological study examined county-level environmental, landscape, and host-related predictors of Lyme disease incidence across Kentucky, Virginia, and West Virginia from 2000-2019. Lyme disease is an emerging public health concern in the Appalachian region, where geographic expansion and shifting ecological conditions may influence disease risk.

Lyme disease case rates (per 10,000 population) were analyzed in relation to climate variables, land cover metrics, host density measures, and rurality using publicly available data sources. Descriptive and regression analyses were conducted to evaluate associations between candidate predictors and disease incidence.

Substantial geographic variation in Lyme disease incidence was observed, with higher case rates …

A Tale Of Two Serpins: Pathologic And Protective Roles Of Agt And Pai-1 In Metabolic And Cardiovascular Disease, Alex C. Pettey

Theses and Dissertations--Physiology

Metabolic and cardiovascular diseases are leading causes of morbidity and mortality worldwide. Conditions such as metabolic dysfunction-associated steatotic liver disease (MASLD), aortic aneurysm, and cardiac fibrosis have limited pharmacological therapies, underscoring the need for deeper mechanistic investigations. Serine protease inhibitors (serpins) have been implicated in these pathologies and represent potential therapeutic targets. Despite structural homology, serpins regulate diverse physiological processes through both protease inhibition and non-inhibitory mechanisms. This dissertation examines the roles of two serpins, angiotensinogen (AGT) and plasminogen activator inhibitor-1 (PAI-1), in preclinical models of metabolic and cardiovascular disease to identify novel mechanisms that may inform future therapeutic strategies. …

Bariatric Surgery Impacts Immune Cell Metabolism And Function Dependent On Metabolic Status, Samantha N. Hart

University of Kentucky Doctoral Dissertations

Type 2 Diabetes (T2D), one of the top ten causes of death worldwide, is fueled by chronic inflammation. T2D is considered a metabolic disease, and there is a great push to target metabolic and associated inflammatory pathways to ameliorate the disease & its comorbidities i.e., obesity and cardiovascular disease. Thus far, clinical trials of anti-inflammatory drugs have had modest impacts on T2D and have not led to changes in clinical practice. This may in part be due to a gap in knowledge in the mechanism(s) driving obesity-associated chronic inflammation. I posit that metabolic abnormalities in immune cells in those with …

Engineering Plga Nanoparticle Size To Modulate Immune Responses After Spinal Cord Injury, Daniel J. Kolpek

University of Kentucky Doctoral Dissertations

Spinal cord injury is a severe and debilitating condition that often results in lifelong complications, including paralysis. Many of these chronic outcomes are driven by a sustained inflammatory response at the injury site, which limits tissue regeneration and functional recovery. As a result, therapeutic strategies that modulate this immune response have gained significant interest. Polymer based nanoparticle therapies have emerged as a promising approach due to their ability to interact with and influence immune cell behavior. Importantly, the physicochemical properties of nanoparticles can be precisely tuned to optimize these effects. Among these properties, size has been shown to influence key …

Disrupted Circadian Rhythms Affect Hallmark Pathologies In Alzheimer’S Disease-Related Mouse Models, Valeria Buzinova

Theses and Dissertations--Molecular and Cellular Biochemistry

Alzheimer’s Disease (AD) is a complex neurodegenerative disease with two hallmark pathologies: extracellular amyloid-b (Ab) and intracellular neurofibrillary tangles (NFTs). Ab is proteolytically processed from amyloid precursor protein (APP) by b-secretase and g-secretase as a monomeric peptide prone to aggregation. Eventually, the aggregate-prone monomers will form dense plaques that are difficult to break down and remove. These plaques begin to deposit into the cortex decades prior to the formation of NFTs and the onset of cognitive decline. NFTs are comprised of hyper-phosphorylated tau. Tau is a protein that serves to promote and stabilize the formation of microtubules. The formation of …

Modeling Inherited Retinal Disease In Zebrafish, Meet Patel

Theses and Dissertations--Biology

Inherited retinal diseases (IRDs) affect millions of people worldwide. Majority of IRDs are caused by degeneration of rod and cone photoreceptor cells (PRCs) due to gene mutations. The overarching goal of my dissertation is to model and evaluate the molecular role of various gene candidates involved in IRDs such as cone rod dystrophy (CRD) and retinitis pigmentosa (RP).

Mutations in CDHR1, a photoreceptor specific cadherin have been associated with CRD and recapitulated in mouse CDHR1 knockouts. However, the molecular function of CDHR1 remains unknown. CDHR1 has been shown to localize at the leading edge of murine rod nascent outer segment …

Evidence-Based Best Practices For Diabetes Education And Self-Care In Appalachia: A Literature Review, Angela J. Occidental, Inga M. Zadvinskis, Jacqueline Hoying

Journal of Appalachian Health

Introduction: The Appalachian Region has a higher prevalence of type 2 diabetes mellitus (T2DM) and associated adverse health outcomes. Although numerous papers report best practices for diabetes care and education, a clinician-friendly, synthesized summary of best practices tailored to Appalachian cultural preferences is lacking.

Purpose: This paper uses the Melnyk & Fineout-Overholt evidence-based framework to identify the best practices for T2DM care and education for Appalachian residents.

Methods: A comprehensive literature search using the databases CINAHL, Academic Search Complete, and PubMed was guided by a PICOT question. Quality appraisals were completed for fifty-two articles; thirty papers were selected to synthesize …

Drive Time Analysis Of New Gynecologic Oncology Patients At West Virginia University, Kassandra Whitfield, Ariel Cohen, Krista Pfaendler, Kristy Ward

Journal of Appalachian Health

Introduction: West Virginia is a rural mountain state; access to medical care, especially specialty care, can be difficult for patients.

Purpose: The purpose of this study is to analyze the geographic status and transportation times of new gynecologic oncology patients.

Methods: Home zip codes for new patient gynecologic oncology patients were analyzed for drive times to the cancer center. Zip codes of oncology providers in the state were compared to the location of patients.

Results: A total of 1,097 new gynecologic oncology patients lived within a 240-minute drive of MBRCC; nearly half (48.9%) of them drove greater than 60 minutes. …

The Effect Of Fructose Metabolism On Hepatic De Novo Lipogenesis And Adipose Tissue Insulin Resistance, Taghreed Ibrahim Fadhul

Theses and Dissertations--Nutritional Sciences

There is a worldwide epidemic of obesity and metabolic dysfunction. The root cause of obesity is driven by a positive energy balance, which is a consequence of increased caloric intake and decreased energy expenditure. Energy intake is the more dominant force, as increasing energy expenditure is a time-consuming and labor-intensive process. The caloric surplus can be mainly accounted for by increased consumption of high-fat and high-sugar diets. While the risks associated with fat consumption are well-documented, the impact of sugar intake is less understood.

Fructose is a simple sugar widely consumed in modern diets. Its intake has been associated with …

Leveraging Clinical Standards To Improve The Translational Relevance Of Therapies For Experimental Spinal Cord Injury, Aaron L. Silverstein

Theses and Dissertations--Neuroscience

Efforts to improve treatment of spinal cord injury (SCI) often use animals to develop effective therapeutics, intending to improve the survival and the quality of life of persons with SCI. Over half of all SCIs in the United States occur at the cervical level and often cause locomotor deficits and life-threatening breathing dysfunction. Thus, my dissertation is focused on this important patient population.

After beginning with a description of translational research and surveying SCI from a clinical standpoint, I turned to describe experimental models of cervical SCI and more detailed neuroimmunological findings relevant to my work. Then, I conducted a …

Zebrafish Models To Uncover Targetable Mechanisms Of Self-Renewal In T-Cell Acute Lymphoblastic Leukemia, Majd Al-Hamaly

Theses and Dissertations--Pharmacology and Nutritional Sciences

Relapsed T-cell Acute Lymphoblastic Leukemia (T-ALL) patients have dismal prognosis, with 5-year overall survival rates of 10% for adults and 36% for children. Relapse is attributed to the inability of chemotherapy agents to eliminate Leukemia Stem Cells (LSCs) that can repopulate the leukemia. Those cells exist with a unique genetic, transcriptomic, and metabolic profile compared to the rest of the leukemia and thus, finding targeted therapies toward this population of cells can result in disease eradication and elimination of relapse. However, investigating LSCs is challenging-particularly in T-ALL- for two reasons: 1) the lack of robust surface markers that define LSCs …

Cell-Type Specific Apoe4 To Apoe2 ‘Switching’ In Astrocytes And Microglia Alters Alzheimer’S Disease Neuropathology, Lesley R. Golden

Theses and Dissertations--Physiology

Apolipoprotein E (APOE) is the strongest genetic risk factor for late-onset Alzheimer’s disease (LOAD). APOE exists in three common protein isoforms throughout the population: ApoE2 (E2), ApoE3 (E3), and ApoE4 (E4). While APOE allele frequencies and the degree of AD-associated risk vary across different ethnic groups, when compared to the ‘neutral’ and most common E3 allele, the E4 allele confers up to a 33-fold increase in Alzheimer’s Disease (AD) risk. Conversely, the neuroprotective E2 allele decreases AD risk by up to 67%. Here, we aimed to determine the therapeutic potential of cell-type specific APOE allele ‘switching’ and explore …

Biochemical And Biophysical Properties Of Failing Myocardium In Rare Patient Populations, Gregory Nathaniel Milburn

Theses and Dissertations--Physiology

Heart failure has diverse underlying etiologies, complicating research. While some types, like ischemic disease or inherited mutations, are well-studied, research on rarer forms has lagged. Understanding the molecular drivers in these populations may enhance diagnostics and therapies. This work examines two rare groups: patients with ATTR cardiac amyloidosis and those receiving mechanical assist device support. We show that myocardium from patients with amyloidosis has increased fibrosis and reduced force production without changes in cross-bridge kinetics. Additionally, we show that the passive stiffness of amyloidosis myocardium is not different from non-failing myocardium, indicating increased ventricular wall thickness may cause restrictive filling. …

Biochemical Properties Of Cardiac Sarcomeres In Human Heart Failure, Austin Grey Wellette-Hunsucker

Theses and Dissertations--Physiology

Heart failure (HF) exhibits considerable heterogeneity, posing significant challenges for research involving human cohorts. Diastolic dysfunction is a common pathophysiological feature; however, its molecular mechanisms remain incompletely elucidated. Sarcomeric proteins are integral to cardiac contraction and relaxation. Nonetheless, the phosphoproteome and the structural remodeling effects of these proteins on diastolic function within the context of HF have not been comprehensively characterized. This study examined sarcomeric modifications in diastolic dysfunction in human HF, focusing on Dilated and Ischemic HF, with non-failing donor hearts as controls. Analyzing myocardial samples from ~150 patients using electrophoretic and biochemical techniques, it found significant titin remodeling …

Rad Reduction Reveals Therapeutic Potential Of Targeting Cardiomyocyte L-Type Calcium Channel Regulation For Heart Failure, Garrett Elmore

Theses and Dissertations--Physiology

Heart failure (HF) is prevalent and is predicted to increase with the aging population. Dilated cardiomyopathy (DCM) is a common cause of systolic HF. Current therapies fail to address principal issues: compromised systolic function and dysfunctional Ca²⁺ handling. No therapeutic approach exists for direct, positive modulation of cardiomyocyte L-type calcium channels (LTCC). RAD (Ras associated with diabetes) is a key regulator of the cardiac LTCC. RAD is a downstream phosphorylated target of the ß-adrenergic receptor (ß-AR)/cAMP/protein kinase A pathway; phosphorylation augments LTCC activity, contributing to chronotropy, inotropy, and lusitropy. RAD overexpression results in LTCC inhibition, whereas knockout positively modulates …

Sex-Specific Roles Of The Adipocyte Mineralocorticoid Receptor In Obesity And Early Life Stress, Meghan B. Turner

Theses and Dissertations--Pharmacology and Nutritional Sciences

Obesity is a burgeoning health epidemic caused by chronic overnutrition and exacerbated by genetic, environmental and developmental factors. The adipocyte mineralocorticoid receptor (MR), a transcriptionally active nuclear receptor, is speculated to contribute to metabolic dysfunction in the obese state. MR expression is increased in obese adipose tissue, and MR modulates the expression of fat-derived hormones such as leptin and adiponectin. In women, obesity can be exacerbated by early life stress, such as adverse childhood experiences (ACEs). Studies show that women display a positive association between cumulative ACE exposures and increased body mass index. Previously, we demonstrated that maternal separation and …

Assessing Chronic Pain Among Adults Diagnosed With Diabetes Residing In Rural Appalachia, Brittany L. Smalls, Adebola Adegboyega, Courtney Ortz, Ellen Combs, Md. Tofial Azam, Philip M. Westgate, Nancy Schoenberg

Journal of Appalachian Health

Introduction: Appalachian populations have some of the highest rates of overdose and comorbidity, all of which are considered risk factors for and contributors to chronic pain.

Purpose: The purpose of this study was to examine the associations of comorbidity, disability (physical limitations), and depression with chronic pain among a community-based sample of Appalachian adults living with diabetes.

Methods: This study used baseline data to conduct a secondary analysis of cross-sectional data (n=356). Data included sociodemographic, disability (physical limitations), chronic pain, and depression measures. These data were collected and analyzed from 2017–2019. Multiple logistic regression was used to investigate the association …

Harmonious Healing: A Review Of Music Therapy, A Humanities-Based Approach To Alzheimer’S Disease Treatment, Rohan K. Desai

Kentucky Undergraduate Journal for the Health Humanities

Alzheimer’s Disease (AD) is a progressive neurodegenerative disease often characterized by memory loss, confusion, and overall cognitive decline. The aging global population has, in recent years, highlighted the fundamental lack of pharmacological treatments for individuals facing an AD diagnosis. In response, a growing body of research has shifted focus to non-pharmacological humanities-based interventions. One such intervention has been music therapy (MT). Music-focused measures have shown great promise as a method of slowing cognitive decline, but mixed results in the literature warrant the need for further investigation. Often, socioeconomic barriers can limit an individual’s access to drug-related treatments, but the affordable …

The Potential Beneficial Role Of Anti-Platelet/Anti-Coagulant Medications On Diabetic Retinopathy: A Scoping Review Protocol, Sarah Draud, Qingjun Wang, Lauren E. Robinson

Markey Cancer Center Faculty Publications

Diabetic retinopathy (DR) is a prevalent microvascular complication of diabetes mellitus (DM, both types 1 and 2), affecting millions of individuals worldwide. DM is known to induce changes in platelet function and hemostasis, thereby elevating the risk of thrombotic incidents. The hyperglycemic environment in DM can trigger platelet hyperactivity, potentially exacerbating the onset and progression of DR. Despite the intricate pathophysiology of DR, which involves oxidative stress, inflammation, retinal neovascularization, and the disruption of the blood-retina barrier, the specific mechanisms underlying platelet hyperactivity in the microvasculature of DM patients remain inadequately explored. Antiplatelet and anticoagulation medications have proven beneficial in …

Long-Term Cardiometabolic Effects Of Preconceptional And Prenatal Opioid Exposure In The Adult Offspring, Nermin Hassan Mohamed Selim Ahmed

Theses and Dissertations--Pharmacology and Nutritional Sciences

Opioid use disorder (OUD), one of the greatest public health threats in the US, requires urgent attention. In 2022, the CDC reported 107,941 overdose deaths, over 70% attributed to synthetic opioids such as fentanyl (FEN). An alarming increase in opioid use disorder (OUD) diagnoses in pregnant people resulted in a 5-fold rise in cases of neonatal opioid withdrawal syndrome (NOWS). This condition elicits sympathetic overactivity, neural hyperexcitability, and a stress reaction characterized by tachycardia and hypertension. Whether prenatal exposure to fentanyl induces cardiovascular dysfunction in the offspring remains undetermined, impeding the timely development of strategies to mitigate OUD-related health risks …

Human Papilloma Virus Type 16 Seroprevalence Among Men Living With Hiv, Ashley Duff

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

Objectives: Individuals living with HIV are at a higher risk for developing human papillomavirus-driven oropharyngeal cancer (HPV-OPC). There are no methods for early detection; however, HPV16 E6 antibodies have been identified as a promising early marker. The objective of this study was to evaluate seroprevalence and predictors of HPV16 E6 seropositivity among men living with HIV.

Methods:2,334 men aged 40+ living with HIV with blood specimens banked within the Tennessee Center for AIDS Research (TN-CFAR) biorepository were evaluated using HPV multiplex serology. Seroprevalence of HPV16 antibodies was calculated for all HPV16 proteins analyzed (L1, E1, E2, E4, E6, E7). …

The Role Of Intracellular Growth During The Systemic Spread Of Listeria Monocytogenes, Jamila S. Tucker

Theses and Dissertations--Microbiology, Immunology, and Molecular Genetics

Listeria monocytogenes is a facultative intracellular pathogen transmitted through the consumption of contaminated food products. Typically, infections range from mild, self-limiting gastroenteritis to life-threatening systemic infections; however, the events that occur in the gut to allow for this spread are unclear.

The focus of my thesis aims to determine how L. monocytogenes escape the mesenteric lymph nodes (MLN), the final barrier to systemic spread for both commensal and pathogenic bacteria in the gut. I have shown that intracellular replication of L. monocytogenes in an as-yet-unidentified cell type is essential for the colonization and dissemination of the bacteria from the MLN. …

Contributions Of The Replication Initiator Protein Dnaa To Physiology And Virulence Of The Lyme Disease Spirochete, Andrew Krusenstjerna

Theses and Dissertations--Microbiology, Immunology, and Molecular Genetics

Borrelia burgdorferi, the etiological agent of Lyme disease, is the most prevalent vector-borne disease in the United States. The spirochetal population is naturally maintained by consistently cycling between Ixodid ticks and small vertebrates. To survive within these diverse niches, B. burgdorferi has evolved a unique physiology and regulatory network to sense and respond to environmental fluxes. Replication is a hallmark of the Lyme spirochete’s enzootic life cycle, specifically at the nymphal tick-to-vertebrate interface. The mechanisms and regulatory schema for the basic cellular processes in B. burgdorferi, or indeed any member of the phylum spirochaetota, are largely unknown. The central hypothesis …

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 …