Medicine and Health Sciences Commons^™

Alterations In Synaptic Structure And Tau Phosphorylation In Alheimer's Disease, Courtney K. Walker

All ETDs from UAB

Alzheimer’s disease (AD) is the most common cause of dementia in individuals over the age of 65. Of the two hallmark pathologies of AD, tau neurofibrillary tangles (NFTs) correlate more strongly with cognitive decline than do Aβ plaques. NFTs form in the entorhinal cortex (EC) and appear in anatomically connected regions over time as disease progresses. This tau spreading may occur via synaptic connections. Most excitatory synapses occur on dendritic spines, which house the postsynaptic machinery. Spines are actin-rich, plastic structures that change their size and shape in response to synaptic activity in a process that is dependent on actin …

The Effect Of Training On Eye Movement While Learning To Use A Non-Foveal Retinal Locus, Jason Eugene Vice

All ETDs from UAB

Vision is our most far-reaching sense. It allows us to quickly detect information about the environment and enhances our ability to interact with the world around us. Accordingly, many neural areas are devoted to obtaining, processing, and interpreting visual information. When vision is impaired through normal aging or disease processes, the functional implications for a person can be quite significant. This is particularly true when a person is deprived of high acuity, central vision. Many people with bilateral central visual impairments learn to compensate for vision loss by adopting a viewing strategy that involves the use of the peripheral retina. …

The Requirement Of Transcriptional Lim Complex Co-Regulators For Pancreatic Endocrine Cell Development And Function, Eliana Davi Toren

All ETDs from UAB

The prevalence and tremendous impact of diabetes mellitus has made glucose regulation of the insulin-producing -cell and surrounding pancreatic islet of Langerhans a center of public and research interests alike. A comprehensive understanding of these hormone-producing cells begins with their developmental origins. What are the genetic cues and participants in the tightly orchestrated process of their formation? Investigating the earliest determinants of islet-cell fate not only allows us to deeply understand mature - and islet-cell function, but also produces a data-driven template for how these cells can be reproduced in future stem-cell based diabetes therapies. LIM transcriptional complexes are indispensable …

Guided Exploration Of Military Servicewomen's Healthcare Experiences And Related Outcomes (Gems Hero), Princess Victoria Jane Nash

All ETDs from UAB

Purpose: This study focuses on factors related to healthcare seeking behaviors and utilization of Veterans Affairs primary care services by female African American Veterans. The purpose of this mixed methods study is to assess what factors influence seeking care at VA healthcare facilities. Research Design: This study used a modified explanatory sequential mixed methods design to assess health services utilization and healthcare experiences of African American female Veterans. This research utilized items from the Health Belief model as a guiding framework to highlight factors that could impact VA healthcare utilization. Methodology: Health services utilization analysis used national data from the …

Evaluating The Association Among Demographic, Disease, And Symptom Profiles And Quality Of Life In Connective Tissue Disease-Related Interstitial Disease, Lanier O'Hare

All ETDs from UAB

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Connective tissue disease-related interstitial lung disease (CTD-ILD) results in an unrelenting symptom burden and may progress to death. The morbidity and mortality associated with CTD-ILD likely has a profound impact on individuals’ quality of life (QOL). Quality of life is a phenomenon that has yet to be sufficiently described in the literature on CTD-ILD. The factors associated with QOL in other chronic lung diseases have been described, but because of the different clinical and demographic characteristics of CTD-ILD, it is unknown if these same factors are associated with QOL in CTD-ILD. The purpose of this study was to examine …

Effects Of Exercise On Cerebral Oxygen Extraction Fraction, Hippocampal Subfields, And Cognition In Older Women, Amani M. Norling

All ETDs from UAB

Cardiorespiratory fitness (CRF) is associated with enhanced cognitive functions in aging. The relationship between fitness and brain function is supported by evidence of improvements or maintenance of gray matter volume, and cerebral blood flow (CBF). Research focused on interactions between CRF and changes in cerebral structure and function have not identified the underlying mechanisms of exercise-induced improvements, and none included the effects of CRF on cerebral oxygen extraction fraction (OEF), which is a measure of the ratio of oxygen that a tissue extracts from the blood to maintain morphological and functional integrity. Here, we present evidence from existing studies that …

The Role Of Alternative Payment Models In Pharmaceutical Services And Outcomes, Matthew G. Parker

All ETDs from UAB

A persistent challenge within the healthcare sector is balancing cost containment for health services and the quality of care associated with these services. This challenge has reinvigorated interest in alternative payment models (i.e., risk-sharing, shared savings, capitation), arrangements between payers and healthcare providers that structure reimbursement for services based on health outcomes. Although much research has assessed the association between these payment models and financial outcomes for medical services, there is a paucity of research that has likewise assessed pharmaceutical outcomes (i.e., electronic prescribing, evidence-based prescribing, medication adherence). The papers comprising this dissertation contribute to this limited body of research …

Synergy Between Stenotrophomonas Maltophilia And Pseudomonas Aeruginosa During Polymicrobial Airway Infections, Melissa Skye Mcdaniel

All ETDs from UAB

Stenotrophomonas maltophilia is a Gram-negative bacillus that can act as an opportunistic pathogen in patients with respiratory diseases, including cystic fibrosis (CF) and ventilator-associated pneumonia. Infection with S. maltophilia is associated with worse lung function, but it remains unclear if this organism contributes directly to lung function decline. Lung infections are often polymicrobial, and S. maltophilia can be isolated from the lung with the key pulmonary pathogen Pseudomonas aeruginosa. In the first half of this work, we investigated the pathogenicity of S. maltophilia alone and during polymicrobial infection with P. aeruginosa. We used respiratory infections in mice to assess persistence …

Nutrition Practices And Body Composition In Infants Born Preterm, Maggie Jerome

All ETDs from UAB

Adequate nutrition and optimal growth are critical goals of clinical care for premature infants in the NICU due to rapid brain growth and development that occur during this time. Emerging evidence suggests that body composition in preterm infants is predictive of neurodevelopmental and metabolic outcomes later in childhood. The objective of this dissertation is to investigate factors affecting premature infant growth and body composition, including high enteral protein supplementation, nutrition during the first two weeks of life, and race of infants born at 22-32 weeks gestational age admitted to the UAB NICU. In a pilot study, 56 preterm infants were …

Relationship Between Neighborhood Deprivation And Epigenetic Age Acceleration With Pain In Adults With Musculoskeletal Pain, Pamela Jackson

All ETDs from UAB

Residents of high-deprivation neighborhoods shoulder a greater burden of age-related health conditions, including experiencing worse chronic musculoskeletal pain outcomes, compared to residents of more affluent neighborhoods. Advancing age is a risk factor for chronic health conditions, which epigenetic modifications may explain. Epigenetic age acceleration occurs when an individual’s epigenetic age is older than their chronological age, and that discordance has been identified as a strong predictor of age-related conditions. Epigenetic age acceleration has also been correlated with neighborhood deprivation. However, the mechanisms for neighborhood disparities in chronic musculoskeletal pain remain unclear. The purpose of this dissertation study was to examine …

Evaluation Of A Living Shoreline Technique On A Southeastern United States Reservoir, Eric V. Muth

All ETDs from UAB

The impoundment of rivers in the southeastern United States has led to the creation of reservoirs that have seen the riparian zone become heavily developed with residential real estate. As the hybrid river/lake systems started forming new shorelines, property owners reacted by attempting to reduce their losses. This has been done in a variety of ways, with the majority falling into the bulkhead category. The use of vertical hard armament has resulted in a loss of ecological function and an increase in erosion of the lakebed at the toe or escarpment. In response to this, the idea was proposed by …

Study Of The Effects Of Contusion Spinal Cord Injury And Optogenetic Stimulation On Lower Urinary Tract Function, Salvador A. Lopez

All ETDs from UAB

Lower urinary tract (LUT) dysfunction is a detrimental ailment that negatively affects a person’s independence, health, and overall quality of life. More specifically, LUT dysfunction as a result of spinal cord injury (SCI) is seen in more than 17,000 cases per year and of those cases, <20% are discharged from care with normal micturition1. Initially, after SCI, there is an acute period of spinal shock when the urinary bladder is flaccid and underactive, while the external urethral sphincter (EUS) that constricts the bladder outlet quickly becomes tonically active. In days to weeks after injury, spinallymediated, reflex bladder contractions re-emerge2-4. Numerous studies have examined aspects of LUT function using various models of SCI, primarily utilizing complete transection injuries. This set of studies first examined the effect of moderate to severe midthoracic contusion SCI on LUT function by examining cystometrogram (CMG) and EUS recordings, bladder/spinal cord morphology, sensory innervation of bladder tissue, and spinal neuronal activation in female mice. This model of SCI produced significant changes in normal bladder function as well as altered bladder morphology, including a robust loss of bladder afferent nerve fibers necessary for micturition. Inhibition of histone deacetylase 6 (HDAC6) has been shown to prevent the loss of sensory nerve fibers in mouse hind paw tissue5, thus HDAC6 inhibition was examined as a possible strategy to prevent the observed loss of sensory nerve fibers in bladder tissue post-SCI. iv Mice were treated using intraperitoneal injections of inhibiting compounds ACY-1083 (10 mg/kg) or Tubacin (5 mg/kg). Treatment resulted in significant improvements in CMG measures and sensory innervation of the bladder wall. Finally, optogenetic stimulation was examined using an adenoassociated virus containing cre-recombinase for cre-dependent expression of channelrhodopsin (ChR2) in both spinal intact and SCI mice. The ability to spare afferent axons in bladder tissue post-SCI through HDAC6 inhibition allowed ChR2 expression in sensory nerve fibers. Direct photostimulation of the bladder using various parameters of duration (1, 2, 5, 10 sec continuous stimulation) and power (0.1mW/mm2, 0.95mW/mm2, 6.50mW/mm2) resulted in the ability to control bladder contractions in both spinal intact (SI) and SCI animals, allowing for on-demand voiding post-injury.

Molecular Imaging Of Cancer For Detection And Monitoring Of Response To Combination Therapy, Tiara S. Napier

All ETDs from UAB

Imaging is a primary component of cancer care and aids in diagnosing, response assessment, and monitoring. Molecular imaging techniques provide visualization of unique tumor biology that can be used to personalize treatment. Key features of an effective biomarker are sensitivity, specificity, and ability to provide clinical value beyond that of other types of information already available at the time of diagnosis. For particularly heterogeneous cancer subtypes, such as glioblastoma (GBM) and triple negative breast cancer (TNBC), reliable biomarkers can be challenging to identify and there are few tar-getable receptors for therapy. Our findings demonstrate that quantifying tumor EGFR (panitumumab-IRDye800CW), granzyme …

Restoring The Sphingolipid Balance In Glioblastoma, Cyntanna C. Hawkins

All ETDs from UAB

Glioblastoma (GBM) is a highly aggressive brain tumor with a median survival of 15 months even with standard of care—surgical resection, radiotherapy, and chemotherapy. Two of the key characteristics contributing to this malignancy are its highly invasive phenotype and resistance to the chemotherapy, temozolomide (TMZ). We, and others, have identified the sphingolipid balance as a driver of these phenotypes with dysregulated sphingolipid metabolism seen in GBM patient samples. The ceramidases, specifically acid ceramidase (ASAH1), mediate the balance between ceramides and sphingosine-1-phosphate (S1P). ASAH1 breaks down ceramides ultimately forming S1P. While ceramides induce cell death, S1P promotes migration and cell survival. …

Cell Type-Specific Diurnal Variation In Hippocampus Physiology, Lacy Kathryn Goode

All ETDs from UAB

Circadian rhythms are biological processes that cycle across 24 hours. Driven endogenously by widely expressed and highly conserved clock genes that compose the circadian molecular clock, circadian rhythms are exhibited in numerous facets of physiology across nearly every tissue throughout the body. Diurnal rhythms in cognition, long-term potentiation (LTP), and the expression of clock genes in hippocampus subfields support a role for circadian regulation of hippocampus physiology. However, little is known regarding the circadian molecular clock and diurnal rhythms in neurophysiology at the cellular level. Here, we characterized diurnal differences in spatial memory, LTP, excitability of and synaptic transmission onto …

The Use Of Vesgen For Analysis Of Retinal Vasculature In Pulmonary Arterial Hypertension, Mariana Desiree Dupont

All ETDs from UAB

Pulmonary artery hypertension is a chronic and progressive disease leading to right heart failure and, ultimately, death if untreated. The goal of the studies in this dissertation was to determine if fluorescein angiography (FA), and color fundus angiography (CF) imaging could be used to garner critical information about retinal changes in individuals with pulmonary artery hypertension (PAH). VESsel GENerational Analysis (VESGEN) is a noninvasive computer program that assigns branching generation to large and small vessels. VESGEN was utilized to investigate vascular alterations in FA, and CF imaging investigating disease progression in PAH. This dissertation demonstrated that PAH patients had aberrant …

Exploring The Influence Of Psychosocial Stress And Inflammatory Properties Of The Diet On Cardiometabolic Risk And Gut Microbiome Health Among Young Adult Women Of Birmingham, Alabama, Rachel Olivia Knight

All ETDs from UAB

Concerning trends for obesity, diabetes, heart attacks, and obesity-related cancers, or cardiometabolic disease (CMD), are developing within the emerging and young adult/adulthood (EYA) population. Evidence supports the concept that chronic stress leads to physiologic dysregulation, reduced mental health, chronic diseases, and reduced longevity; however, these are not inevitable outcomes, and resilience or vulnerability is determined by interacting environmental and biobehavioral factors. Although CMD manifests clinically in older adulthood, disease pathophysiology begins earlier, and thus, EYA is a critical time for observation and intervention. Growing evidence indicates inflammation is a major risk factor in CMD development and may be exacerbated by …

Three Heads Are Better Than One: A Structural Look At Staphylococcal Bacteriophage Capsids, N'Toia Chivon Hawkins

All ETDs from UAB

Staphylococcal species such as S. aureus and S. epidermidis are opportunistic pathogens that are the leading causes of nosocomial infections. They have become of growing concern due to the virulence factors that they have acquired as well as their inability to be treated due to resistance to antibiotics. Bacteriophages have increasingly become a popular contender for eliminating these pathogens, however not every phage is suitable for the job. Size of the genome, life cycle, the ability to mobilize genomic material, and host range all factor into how well-suited a phage is to be used as a therapeutic. In this dissertation …

Predicting Change In Quality Of Life In Patients With Advanced Cancer And Family Caregivers Using Gps Data, Kyungmi Lee

All ETDs from UAB

Patients with advanced cancer and their family caregivers often experience poor quality of life. Measuring patient and caregiver physical and mental quality of life is typically performed using participant reported outcome measures, especially validated questionnaires. However, this self-report approach has several limitations, including recall bias, respondent burden, and social desirability bias. One potential solution to these limitations may be to use passive data collected by personally owned smartphones (e.g., GPS data) to model and assess the quality of life in family caregivers and patients with advanced cancer. Yet, there is no evidence to date that passively collected smartphone data is …

Hedgehog Signaling Rewires M2 Macrophage And Regulatory T Cell Metabolism Within The Tumor Microenvironment Of Breast Cancer, Dominique C. Hinshaw

All ETDs from UAB

Current treatments for breast cancer offer little relief to patients with metastatic disease. A contributory factor to tumor growth and metastasis is aberrant up-regulation of developmental signaling pathways such as the Hedgehog (Hh) signaling pathway. This pathway is aberrantly activated in breast cancer and contributes to tumor progression and metastasis. The success of these events is highly influenced by the surrounding immune microenvironment. Macrophages exist along a spectrum of M1 (tumor-eradicating) to M2 (tumor-promoting), while regulatory T cells (Tregs) are an immunosuppressive cell type. The predominant functions of M2 macrophages and Tregs include dampening the immune response and promoting wound …

Palliative Care Experiences And Educational Needs Of Healthcare Interprofessionals In Jamaica: A Mixed Methods Study, Rebecca L. Edwards

All ETDs from UAB

Universal access to palliative care (PC) is a human right that much of the world has not accomplished and educating a PC workforce is critical to PC advancement. Higher PC disparities exist in low-and-middle income countries, such as Jamaica. The World Health Organization Public Health Model and the International PC Initiative’s PC roadmap emphasize the importance of PC education. The purpose of this mixed methods dissertation study was to investigate the PC experiences and educational needs of healthcare interprofessionals who provide care for patients with late-stage serious illnesses in Jamaica. Three specific aims incorporated quantitative investigation of physicians’, nurses’, and …

Intrinsically-Photosensitive Retinal Ganglion Cells And Their Functional Roles, Kevin Q. Chang

All ETDs from UAB

This project was conducted in Old World monkeys and focused on characterization of the intrinsically photosensitive retinal ganglion cells (ipRGCs) as they pertain to the pupillary light reflex, as well as on the neuroanatomical and electrophysiological characterization of the suprachiasmatic nucleus (SCN) of the hypothalamus as it pertains to circadian rhythms. A custom antibody was developed against the human melanopsin gene. We validated the antibody using western blot and immunohistochemistry. The functional role of ipRGCs in driving pupillary responses was investigated through immunotoxin-induced ablation in Rhesus macaques with the antibody conjugated to saporin. As hypothesized, the pupillary light reflex and …

Health Disparities In Cardiometabolic Risk Among African American And European American Adults, Catharine A. Couch

All ETDs from UAB

African American (AA) individuals are disproportionately burdened by cardiometabolic disease, including type 2 diabetes (T2D) and cardiovascular disease (CVD), and associated risk factors. The objective of this dissertation research was to investigate pathophysiological and lifestyle contributors to racial disparities in cardiometabolic disease including beta-cell dysfunction, ectopic fat, the natriuretic peptide system, and diet. These first three risk factors, beta-cell dysfunction, ectopic fat, and the natriuretic peptide system, were explored in a cross-sectional study of young AA and European American (EA) adults. The fourth risk factor, diet, was explored in a large, national cohort of black and white adults. First, we …

Multilevel Influences On Physical Activity Participation In Rural And Cancer Populations With Obesity, Nashira Inika Brown

All ETDs from UAB

espite the strong evidence of physical activity benefits, the prevalence of physical inactivity and associated obesity continues to increase. Rural and cancer survivor populations with obesity, in particular, remain highly inactive and are at increased risk of comorbidities. Thus, physical activity interventions are needed to promote active lifestyles. However, before developing or adapting existing multi-level physical activity interventions, more research is needed to understand the necessary components to meet the needs and preferences of these unique populations. Therefore, this project involved identifying the gaps in literature followed by three studies to investigate the multilevel influences on physical activity in rural …

Comprehensive Characterization Of Structural Variations Using Long-Read Sequencing Data, Yu Chen

All ETDs from UAB

Structural variants (SVs) contribute to genomic diversity and play pathogenic roles in a wide range of genetic disorders. Accurate characterization of SVs is critical for genomic research and studies of disease mechanisms. The rapid development of Third-Generation Sequencing (TGS) technologies has largely increased sequencing read length compared to Next-Generation Sequencing (NGS), bringing both great potentials and challenges in SV discovery through alignment-based and assembly-based approaches. In order to take full advantage of TGS data, I have developed a suite of bioinformatics tools focusing on comprehensive characterization of SVs. For the alignment-based SV discovery, I have developed DeBreak to identify SVs …

Il-22 Mediated Host Defense During Attaching-Effacing Pathogen Infection, Baiyi Cai

All ETDs from UAB

Intestinal infections are a cause of morbidity and mortality worldwide and remain a public threat. Interleukin (IL)-22 is central to host immune responses in the intestine during infection and inflammation. IL-22 can be produced by both innate and adaptive immune cells, yet their relative contributions to host protection remain unclear. Here we demonstrated the specific role and mechanism for IL-22 from innate and adaptive sources to protect the host. Using the Citrobacter rodentium (C.r) model, we found that IL-22 from innate cell, protect the host during early infection. IL-22 induces epithelial production of polymorphonuclear neutrophils (PMN) recruiting chemokine CXCL1, CXCL2 …

Distinct Clinical Manifestations Associated With Autoantibodies And Cytokines In Systemic Lupus Erythematosus, Fatima K. Alduraibi

All ETDs from UAB

Objective: Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by production of autoantibodies (autoAbs) and cytokines. Moreover, lupus nephritis (LN) occurs in approximately 50% of SLE patients. AutoAb and cytokine levels produced by B and T cells are high in LN patients, although their relationship with histological patterns requires investigation. Methods: We analyzed the relationship between B cell cytokines and major T cell cyto-kines, including their association with autoAbs, and the clinical manifestations of SLE, especially LN. We also analyzed endogenous intracellular interferon beta (IFNβ) expression in the peripheral blood mononuclear cells and serum circulating nephritogenic autoAbs from …

A Randomized Controlled Trial To Compare The Histomorphometric And Clinical Outcomes Of Soft Tissue Augmentation At The Time Of Lateral Ridge Augmentation Procedures, Kenneth Liu

All ETDs from UAB

Guided bone regeneration (GBR) can be used to augment deficient alveolar ridges in preparation for dental implant placement. Mucogingival deformities can result from the periosteal releasing incision during GBR. This can be addressed by additional soft tissue augmentation procedures to increase the width of keratinized tissue and vertical soft tissue thickness, both of which have demonstrated clinical benefits around implants. The drawbacks of soft tissue augmentation following ridge augmentation include an additional procedure, increased patient morbidity, and less patient acceptance of treatment. In general, soft tissue augmentation can be performed at various time points throughout treatment, but literature on soft …

Evaluation Of Flexural Strength, Modulus, Translucency, Stain Resistance, And Gloss Of Different 3d Printing Materials, Shantanu Mankar

All ETDs from UAB

Background: 3D printing, the next step in digital dentistry, has improved the technical accuracy in treating patients. There are many advantages of 3D-printed techniques in the field of prosthodontics. It can be clearly experienced from an intraoral scanner, with its digital data, making many physical working models. With the recent 3D-printed, we can eliminate the traditional impression technique, similar to the fabrication procedure. The milling method, which includes a computerized programmed pattern of cutting the material with, but can be a wastage of materials along with producing noise, heat, and other components (Park, Ahn, Cha, & Lee, 2018)Objectives: To evaluate …

Investigation Into The Structure And Function Of Streptococcal Antigen I/Ii Family Of Proteins, Joshua L. Mieher

All ETDs from UAB

Streptococci are involved in the infections of the oral cavity as well as at various sites throughout the body. Their initial contact with tissues/surfaces is enabled by adhesins present on the microbial surface. Among these the Antigen I/II- family (AgI/II) of adhesins are known be important factors in these infections as they enable adherence to multiple host proteins thus allowing the bacteria to gain a foot hold. In this thesis, we have structurally and functionally characterized yet another adhesin on S. mutans, the glucan binding protein C, which resembles the V-region of AgI/II. In addition, we have also resolved the …