Associations Among Psychosocial Factors, Health-Related Quality Of Life, And Adherence In Pediatric Inflammatory Bowel Disease, Cecelia I. Nelson

Graduate Theses, Dissertations, and Problem Reports

Inflammatory Bowel Disease (IBD) is a prevalent disorder among youth in the United States. IBD is one of the leading causes of chronic pain in adolescence and symptoms can lead to reduced quality of life, social embarrassment, and lower self-esteem. Adherence to medical regimens for IBD is incredibly important to prevent morbidity, mortality, and impaired health-related quality of life (HRQOL). However, adolescents struggle generally with adherence and the regimen for IBD can be complicated and include aversive side effects. Psychological factors, such as depressive symptoms, are key factors associated with non-adherence. Nevertheless, gut-specific anxiety (GSA) is a psychological factor that …

Expansion On The Use Of The Novel Compound, Elp-004, Using A Mycobacterium Tuberculosis Experimentation Model, Kendyl Marie Berry

Graduate Theses, Dissertations, and Problem Reports

Osteoarticular tuberculosis (OAT) is a bone degenerative disease that results in bone erosion, joint effusion, joint swelling, and sometimes, nerve compression. OAT occurs from the hematogenous dissemination of Mycobacterium tuberculosis (Mtb) bacilli spreading from the primary site of infection to the bones and joints; the primary site of infection tends to be the lungs as pulmonary tuberculosis infections are the most common. OAT can occur as the result of an active or latent infection. Latent infections result in OAT when bacilli are able to escape granulomas. The incidence of OAT is not as high as pulmonary infections, making up about …

Burkholderia Collagen-Like Protein 8, Bucl8, Is An Outer-Membrane Component Of A Novel Efflux Pump And Immunogenic Vaccine Candidate, Megan Elizabeth Grund

Graduate Theses, Dissertations, and Problem Reports

Burkholderia spp. are Gram‐negative intrinsically resistant bacteria that are responsible for environmental and nosocomial infections of clinical and biodefense concern. Our laboratory previously identified in silico Burkholderia collagen-like protein 8 (Bucl8) in the BSL-3 pathogens Burkholderia pseudomallei and Burkholderia mallei (Figure 1). The protein sequence of Bucl8 contains tandem outer-membrane efflux protein domains (OEP) typical of efflux systems and a unique collagen-like domain (CL) consisting of a repeating sequence of Glycine-Alanine-Serine (GAS). Because efflux pumps are often a mechanism of pathogenicity and antibiotic resistance, we investigated Bucl8 further. Here, we determined that the locus of bucl8 contains genes …

Evaluation Of A Novel Mrna-Pertussis Vaccine Against Emerging Clinical Isolates Of Bordetella Pertussis, Graham Jeffrey Bitzer

Graduate Theses, Dissertations, and Problem Reports

Bordetella pertussis is a Gram-negative obligate aerobe that causes a respiratory disease known as pertussis or whooping cough. Pertussis is most severe in younger children, especially infants but the bacteria has been known to colonize adult populations. Before the introduction of the whole-cell pertussis (wP; wP-DTP) vaccine reported numbers of pertussis cases within the US routinely topped 100,000 cases per year. However, with the widespread usage of the wP vaccine case numbers began dropping and reached a low of less than 5,000 cases per year in the late 1970’s and early 80’s. It appeared that B. pertussis was heading towards …

A Machine Learning Approach For Early Diagnosis Of Transthyretin Amyloid Cardiomyopathy Among Heart Failure Patients, Tanjim Ahmed

Graduate Theses, Dissertations, and Problem Reports

Transthyretin Amyloid Cardiomyopathy (ATTR-CM) is a rare, progressive, and fatal disease. Prevalence of ATTR-CM ranges from 4 to 17 per 100000 cases where the mean survival time is less than 4 years. It has a history of being underdiagnosed and misdiagnosed. The diagnosis delay has a weighted mean of 6.1 years for wild-type ATTR-CM. Low awareness, the necessity of invasive procedures, and lack of treatment are the key reasons for delayed diagnosis. But, with the introduction of non-invasive tests like nuclear scintigraphy with ^99mTC-PYP and the disease modifying drug Tafamidis, the diagnosis delay signifies a missed opportunity to increase …

Understanding Vaccine-Induced Memory Responses To Develop The Next Generation Of Pertussis Vaccines, Kelly L. Weaver

Graduate Theses, Dissertations, and Problem Reports

Bordetella pertussis is a Gram-negative respiratory pathogen that can infect individuals of all ages and is notably responsible for infant fatalities. Pertussis (whooping cough) is a vaccine-preventable respiratory disease for which vaccines have been available in the United States since the 1940s. Whole cell pertussis vaccines kept incidence of pertussis under 5,000 cases per year, but were associated with reactogenicity issues. Following the introduction of less reactogenic acellular pertussis vaccines in the late 1990s, there have been noteworthy outbreaks of pertussis. For example, in 2012 there were over 50,000 reported cases of pertussis and 20 deaths in the U.S. The …

Evaluation Of A Comprehensive Diabetes Mellitus Protocol At A Rural, Federally Qualified Health Center In Southern West Virginia, Hannah D. Davis

Graduate Theses, Dissertations, and Problem Reports

Background: Diabetes mellitus is a chronic disease that affects nearly 34 million Americans. In rural Appalachia, the population is affected disproportionately at a rate of 14% compared to the national average of 10%. Diabetes is a lifelong, chronic condition managed best by a multidisciplinary team-based approach to achieve optimal disease control. Best practices in the care of diabetes support the use of evidenced based care protocols and leveraging technology to decrease the burden of disease. Type 2 diabetes mellitus (T2DM) is the most common type, making it the focal population for evaluation.

Purpose: The purpose of this project was to …

Influences Of Disrupted Circadian Rhythms On Stroke Outcome, Jennifer A. Liu

Graduate Theses, Dissertations, and Problem Reports

The circadian system is composed of a subset of temporal oscillators that function through a transcriptional and post-translational molecular and functional negative feedback loop cycling approximately every 24 hours. The central clock located in the suprachiasmatic nucleus is responsible for entrainment using light as the key timekeeper (zeitgeber); it is responsible for synchronizing and optimizing physiological behavior and function to the environment. Exogenous information, such as day length and light-dark cycles, provide critical temporal cues for adjusting to environmental conditions. Proper alignment to natural light dark cycles and circadian rhythms is optimal for vital health, fitness, and survival in organisms. …

Developing An Evaluation Process For Telehealth In A Copd Clinic, Jodi H. Biller

Graduate Theses, Dissertations, and Problem Reports

Background: Telehealth was broadly implemented as a care modality in response to a worldwide pandemic in 2020. Before the COVID-19 pandemic, while telehealth was not new, it was not widely utilized at the project site location, and a uniform method of evaluating its effectiveness was needed. This quality assurance project developed and piloted a uniform process to evaluate telehealth in a Chronic Obstructive Pulmonary Disease (COPD) clinic, then evaluated stakeholder perceptions about the process used in developing the evaluation tool.

Methods: The telehealth evaluation tool was developed using the National Quality Forum (NQF) framework and Global Obstructive Lung Disease (GOLD) …

Amelioration Of Mitochondrial Bioenergetic Dysfunction In Diabetes Mellitus: Delving Into Specialized And Non-Specific Therapeutics For The Ailing Heart, Andrya Jean Durr

Graduate Theses, Dissertations, and Problem Reports

Morbidity and mortality of the diabetic population is influenced by many confounding factors, but cardiovascular disease (CVD), remains the leading cause of death. Mitochondrial dysfunction is central in the development of cardiac contractile dysfunction, with decreased mitochondrial bioenergetic function, increased dependence on free fatty acid utilization, and a decrease in glucose utilization having been shown to contribute to contractile dysfunction. Strategies targeting the amelioration of mitochondrial bioenergetic function are attractive for limiting diabetes-induced heart failure, and preserving health-span. The goals of this dissertation were to assess two mitochondrial-centric approaches for the amelioration of mitochondrial and cardiac contractile dysfunction in diabetes …

Low- And High-Wattage Vaping During Pregnancy Influence Aortic Structure And Function In Rat Offspring, James Ian Frazier

Graduate Theses, Dissertations, and Problem Reports

Introduction: Electronic cigarettes (e-cigs) are being marketed as a healthier alternative to traditional cigarettes, yet the health consequences of e-cig usage (also called vaping) are still being investigated. E-cigs are easily customized for user preferences. For example, the choice of flavors, nicotine concentration, and/or the temperature (i.e., wattage) used to heat the e-liquid can be selected in many devices. Emerging evidence suggests that vaping during pregnancy impairs cerebral vascular function in rodent offspring. In this study, we sought to investigate the potential effects of changes to e-cig device wattage (i.e., 5W vs. 30W) with maternal vaping during pregnancy on vascular …

Utilizing The K18-Hace2 Mouse Model To Develop Protective Covid-19 Vaccines, Ting Y. Wong

Graduate Theses, Dissertations, and Problem Reports

The ongoing Coronavirus Disease 2019 (COVID-19) pandemic is caused by the respiratory virus Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Similar to other respiratory viruses, SARS-CoV-2 is transmitted through inhalation of respiratory droplets and aerosols from infected individuals. Once inhaled, SARS-CoV-2 utilizes the receptor binding domain (RBD) on the spike protein to bind to human Angiotensin Converting Enzyme 2 (hACE2) receptor to gain entrance into host cells to begin viral replication. SARS-CoV-2 infection can result in mild to severe cases of COVID-19 ranging from asymptomatic infections, cold or flu like symptoms to respiratory failure. The onset of the pandemic in …

Maternal Engineered Nanomaterial Inhalation Exposure: Cardiac Molecular Reprogramming In Progeny Through Epigenetic And Epitranscriptomic Mechanisms, Amina Kunovac

Graduate Theses, Dissertations, and Problem Reports

Introduction: Nano-titanium dioxide (TiO₂), a prominently utilized engineered nanomaterial (ENM), is being employed for its physiochemical properties in several fields including the food industry, manufacturing, and biomedicine. As the prevalence of this ENM, and other particulate matter grows, so does the concern for antagonistic consequences on long-term heart function in vulnerable populations, which until now have not been investigated. Due to the reliance of the heart on the ATP generating capacity of mitochondria for contraction, understanding the role of mitochondrial bioenergetics and structure is pivotal in understanding the repercussions of particulate matter exposure during gestation. As the mass …

Targeting The Cerebrovasculature In Sepsis: A Focus On The Brain Microvascular Endothelium, Divine C. Nwafor

Graduate Theses, Dissertations, and Problem Reports

The blood-brain barrier (BBB) is a critical interface between the systemic circulation and the brain. It is a specialized multicellular unit composed of brain microvascular endothelial cells (BMECs), pericytes, a basement membrane, and astrocytic end foot processes. BMECs are a principal component of the BBB that provide the structural framework needed for the stringent transport of molecules into the brain. BMEC dysfunction permits the trafficking of neurotoxins from systemic circulation into the brain, which ultimately exacerbates BBB dysfunction and neuroinflammation. Studies have shown that BBB dysfunction is a key determinant of cognitive decline in sepsis. However, there are critical knowledge …

Mitochondrial Aspects Of Neuronal Pathology In Triple-Transgenic Alzheimer’S Disease Mice, John Zachary Cavendish

Graduate Theses, Dissertations, and Problem Reports

Alzheimer’s disease (AD) is a fatal, progressive neurodegenerative disease afflicting millions of people in the United States alone and is the only one of the top leading causes of morbidity and mortality with no effective disease-modifying therapies. It is the most common form of dementia, affecting one in three people over the age of 85. While the hallmarks of the disease include accumulation of beta-amyloid-based extracellular plaques and hyperphosphorylated tau-based intracellular neurofibrillary tangles, treatment strategies centered on removing or mitigating these components of AD have all failed in humans. Mitochondrial dysfunction has been increasingly recognized as an early and consistent …

Nitrite Supplementation Restores Aortic Health In Chronically Stressed Mice, Tyler Coblentz

Graduate Theses, Dissertations, and Problem Reports

Chronic stress increases the risk of developing cardiovascular disease potentially via increases in elastic artery stiffness and endothelial dysfunction. Decreased bioavailability of the potent vasodilator nitric oxide (NO) describes a hallmark of endothelial dysfunction. Nitrite reduces into active NO, providing an alternative pathway of NO restoration. The effect of nitrite supplementation on aortic endothelial function has yet to be determined in chronically stressed mice. We hypothesized that nitrite supplementation would rescue chronic stress-attributed impairments in aortic endothelial function.

Mice at 18 weeks of age underwent an unpredictable chronic mild stress (UCMS; 5 days/week for 7 hrs/day) paradigm to elicit a …

A Role For Endothelial Tissue-Nonspecific Alkaline Phosphatase In Blood-Tissue Barrier Health And Disease, Allison L. Brichacek

Graduate Theses, Dissertations, and Problem Reports

Sepsis is a disorder that targets the microcirculation with significant effects at blood-tissue barriers such as the blood-brain barrier (BBB) and gut-vascular barrier (GVB). Intestinal barrier dysfunction is thought to be one of the most important contributors to multi-organ dysfunction in sepsis. As a common site of infection, the impaired gut allows the dissemination of bacteria, which exacerbates the disease pathophysiology, and can lead to long-term morbidity and mortality. The mechanisms that influence altered barrier permeability in the GVB in sepsis and other inflammatory disorders are not well understood. Tissue-nonspecific alkaline phosphatase (TNAP) enzyme activity, which has been shown to …

Bypassing The Blood-Brain Barrier: A Physical And Pharmacological Approach For The Treatment Of Metastatic Brain Tumors, Samuel A. Sprowls

Graduate Theses, Dissertations, and Problem Reports

This dissertation (a) provided an in depth literature review of methods to disrupt the BBB/BTB and improve therapeutic distribution to brain tumors, (b) evaluated the use of azacitidine as a single agent therapy for the treatment of brain metastasis of breast cancer and a potential molecular mechanism by which brain tropic cells are sensitized to hypomethylating agents, (c) determined the impact cannabidiol has on P-glycoprotein mediated efflux at the blood-brain barrier and its potential for use as a single agent treatment for metastatic brain tumors, (d) developed a preclinical radiation therapy protocol for use in small animals and in vitro …

Grouping Algorithms For Informative Array Testing In Disease Surveillance, David Sokolov

Graduate Theses, Dissertations, and Problem Reports

In order to maintain normal operations and prevent unnecessary morbidity and mortality during times of disease outbreak, institutions find a need to conduct frequent and widespread testing of their constituents, often under significantly limited testing resource constraints. Faced with the challenge of how best to allo- cate these limited resources to maximum effect, institutions are increasingly turning to group (or “pooled”) testing, which involves testing strategically-chosen groups of patient samples rather than individual samples, producing significant testing resource savings under certain regimes of disease prevalence. While group test- ing can be conducted without any a priori knowledge of individual disease …

Targeting Calcium Homeostasis For The Treatment Of Multiple Myeloma, Osama M. Elzamzamy

Graduate Theses, Dissertations, and Problem Reports

Multiple myeloma (MM) is a hematological malignancy characterized by the neoplastic proliferation of the plasma cells. MM is a relatively rare cancer that accounts for about 1.8% of all cancers and is the second most common hematologic malignancies, and despite the advancement from untreatable to treatable malignancy, it is yet incurable. Calcium ions (Ca²⁺) play an important role as second messengers in regulating a plethora of physiological and pathological processes, hence cytoplasmic Ca²⁺ is tightly regulated with strict spatial and temporal control to initiate, maintain, and terminate appropriate signaling pathways and phenotypes including cellular proliferation, cell cycle …

From Inner Segment To Outer Segment: Palmitoylation Of Photoreceptor Na+, K+-Atpase And The Importance Of Prcd In Photoreceptor Outer Segment Morphogenesis, Emily R. Sechrest

Graduate Theses, Dissertations, and Problem Reports

Photoreceptors are specialized neuroepithelial cells which are optimized for efficient capture of light and initiation of visual transduction. These cells have several compartments which are very important for proper visual function and segregation of cellular processes, including the outer segment (OS), inner segment (IS), nucleus, and synapse. The IS houses all of the cellular organelles and biosynthetic molecular machinery the cell requires and is the site of protein synthesis. The light-sensing OS is a highly modified, primary cilium, which contains many stacks of double membranous discs which house proteins required for formation and maintenance of OS structure, as well as …

Cerebrovascular Dysfunction And Degeneration In Alzheimer’S Disease Pathophysiology, Dominic Dimitri Quintana

Graduate Theses, Dissertations, and Problem Reports

Alzheimer’s disease (AD) is a terminal illness and the most common form of dementia, which disproportionately affects the aged population. The pathophysiology of AD is characterized by neurodegeneration that slowly progresses, affecting regions of the brain that are involved in learning, memory, language, and executive function. In patients with the disease, early symptoms include non-disruptive forgetfulness that evolves into the inability to form new memories and ultimately the loss of autonomy at late stages. Histopathological hallmarks in the brain from patients with AD is the presence of amyloid-β (Aβ)-plaques and neurofibrillary tangles (NFT) deposited in the parenchyma. Since the discovery …

Role Of Ciliary Proteins Adp Ribosylation Factor Like Gtpase 13b (Arl13b) And Bardet-Biedl Syndrome-8 (Bbs8) In Photoreceptor Outer Segment Morphogenesis, Maintenance, And Viability, Tanya L. Dilan

Graduate Theses, Dissertations, and Problem Reports

Photoreceptor neurons are modified primary cilia with an extended ciliary compartment known as the outer segment (OS). The mechanisms behind the elaboration of photoreceptor cilia, OS morphogenesis, and maintenance remain poorly understood. In this work, we focused on dissecting the role of two ciliary proteins, the small GTPase ADP-ribosylation factor-like GTPase 13B (ARL13B) and Bardet-Biedl Syndrome-8 (BBS8) in the context of photoreceptor biology. Both BBS8 and ARL13B are linked to defects in ciliogenesis (cilia development) and Retinitis Pigmentosa (vision loss). ARL13B is implicated in regulating ciliary length, and BBS8 is part of the Bardet-Biedl Syndrome complex (BBSome); the BBSome is …

Multimorbidity, Immune Checkpoint Inhibitor Use, And Healthcare Expenditures Among Older Patients With Late-Stage Melanoma, Pragya Rai

Graduate Theses, Dissertations, and Problem Reports

With decades of unchanged cancer care with no added survival benefit, immune checkpoint inhibitors (ICI) changed the treatment landscape of late-stage melanoma in 2011. A key factor in determining the use of ICIs is the presence of pre-existing chronic conditions, which can influence the outcome. However, the prevalence of multimorbidity (defined as presence of two or more chronic conditions) among older patients with late-stage melanoma remains unknown. It also remains unknown if the presence of multimorbidity factors into the use of ICIs. Hospital-related factors associated with ICI use have been studied. Yet, patient-level factors, such as age, sex, marital status, …

Understanding The Host Immune Response Against Pseudomonas Aeruginosa To Develop Novel Therapeutics And Vaccines, Emel Sen Kilic

Graduate Theses, Dissertations, and Problem Reports

Pseudomonas aeruginosa is a Gram-negative opportunistic bacterium that causes a broad range of acute and chronic infections. The high adaptability and emergence of multidrug-resistant strains of this bacterium pose a significant threat to human health. Particularly, pneumonia caused by this pathogen is associated with high morbidity and mortality in immunocompromised patients. To prevent these infections, we aimed to develop novel vaccine strategies by characterizing the host immune response against P. aeruginosa. During respiratory infections, P. aeruginosa first contacts with epithelial cells along the respiratory tract. Using RNA-sequencing, we were able to characterize transcriptional changes of the epithelial cells in …

Effect Of Western Diet And Caloric Substitution With Apple Pomace On Fatty Acid Composition And Gene Expression In The Hypothalamus Of Growing Female Sprague-Dawley Rats, Ayad Abdulhamid Alawadi

Graduate Theses, Dissertations, and Problem Reports

The hypothalamus plays a major role in regulating food-intake and energy-expenditure. Hypothalamic dysfunction implicated in neurodegenerative diseases is characterized by diet-induced neuroinflammation and energy dysregulation. Apple pomace, a waste byproduct of processing, is rich in polyphenols and soluble fibers, has the potential to ameliorate diet-inducing inflammation. The objective of this study was to determine the effects of Western diet and caloric substitution of Western diet with 10% apple pomace on brain fatty acid composition and gene expression related to hypothalamic function and health in growing female rats. Growing female Sprague-Dawley rats (age 22-29 days) were randomly assigned (n=8 rats/group) to …

Environmental Regulation Of The Heart: The Role Of Non-Coding Rna And Epigenetics In Influencing Mitochondrial And Cellular Health, Quincy Alexander Hathaway

Graduate Theses, Dissertations, and Problem Reports

The mitochondrion, a small but ubiquitously distributed organelle in the cell, continues to be the focus of many disease pathogeneses, tissue and organ dysfunctions, and other morbidities that occur throughout the body. The purpose of this work was to understand how cardiac mitochondrion are altered in disease and pathological states, specifically in their adaptation to environmentally stimulated regulatory networks, such as epigenetic modifications and promotion/inhibition of non-coding RNAs. Acute stress to mitochondrial regulation (inhalation toxicology) as well as chronic (type 2 diabetes mellitus) was examined. Using a FVB transgenic microRNA-378a mouse knockout model, the cardiovascular impact derived from altering the …

The Life And Work Of Alex Klein, Ramon Thiago Mendes De Oliveira

Graduate Theses, Dissertations, and Problem Reports

Alex Klein is one of the best-known figures of the American oboe school. He is the winner of multiple international competitions, including the first prize at the Geneva’s Concours International d’Execution Musicale. Appointed principal oboe at the Chicago Symphony Orchestra in 1995, Klein is one of the most highly regarded musicians hired during the Barenboim era. His recording of Richard Strauss’ oboe concerto with the CSO was awarded Best Instrumental Soloist Performance (with Orchestra) at the 44th Grammy Awards. In 2004, his tenure at CSO was interrupted due to the onset of Focal Dystonia; which affected multiple fingers in …

Predictors And Health Outcomes Of Treatment-Resistant Depression Among Adults With Chronic Non-Cancer Pain Conditions And Major Depressive Disorder, Drishti Shah

Graduate Theses, Dissertations, and Problem Reports

Understanding major depressive disorder (MDD) as a comorbidity in patients with chronic non-cancer pain conditions (CNPC) is of importance because of the high prevalence and well documented bi-directional relationship between MDD and pain. Furthermore, presence of CNPC among adults with MDD often reduces benefits of antidepressant therapy, thereby increasing the possibility of treatment resistance. Treatment-resistant depression (TRD) commonly defined as insufficient response to multiple antidepressant trials, often worsens depression and pain symptoms and can amplify the clinical and economic burden among adults with CNPC and MDD. Additionally, long-term opioid therapy (LTOT) may be prescribed at a higher rate to adults …

Adaptation Of The Streptococcal Collagen-Like Protein 1, Scl1, Of Group A Streptococcus To Recognize Fibronectin Type Iii Repeats, Dudley H. Mcnitt

Graduate Theses, Dissertations, and Problem Reports

Background: Group A Streptococcus (GAS) is responsible more than 700 million infections worldwide each year. Most of these infections start with initial colonization of the throat and skin, which is augmented by surface adhesins. The streptococcal collagen-like protein 1 (Scl1) is a major adhesin expressed by GAS that contains an N-terminal sequence-variable (V) domain, protruded away from the cell surface by the collagen domain. The Scl-V domain is comprised of three pairs of anti-parallel α-helices interconnected by surface-exposed loops. For attachment, GAS adhesins require a portal of entry, such as a wound or breach in the epithelium, to enter …