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The Role Of Pim Kinases In Hepatoblastoma Tumorigenicity, Stem Cell-Like Cancer Cell Maintenance, And Chemoresistance, Laura Lee Stafman Jan 2018

The Role Of Pim Kinases In Hepatoblastoma Tumorigenicity, Stem Cell-Like Cancer Cell Maintenance, And Chemoresistance, Laura Lee Stafman

All ETDs from UAB

Hepatoblastoma is the most common primary liver malignancy in children. Despite increasing incidence, treatment has not changed significantly in the past 20 years, making the need for novel therapeutics imperative. Proviral Integration site for Moloney murine leukemia virus (PIM) kinases are a family of serine/threonine kinases that have been implicated in multiple other cancer types including the adult liver cancer, hepatocellular carcinoma. Emerging evidence has begun to elucidate a role for PIM kinases in stem-cell like cancer cells (SCLCCs). This subpopulation of cells is thought tobe responsible for tumor maintenance, recurrence, metastasis, and chemoresistance. Chemoresistance is a significant barrier to …

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The Role Of Glycosylation Initiation By Galnac-Ts In Iga Nephropathy, Tyler Stewart Jan 2018

The Role Of Glycosylation Initiation By Galnac-Ts In Iga Nephropathy, Tyler Stewart

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The autoimmune disease IgA nephropathy (IgAN) is a common cause of primary glo-merulonephritis, often resulting in end-stage renal disease. IgAN patients have elevated serum levels of immunoglobulin A1 (IgA1) with autoantigenic galactose-deficient (gd) O-glycans. The gd-O-glycans occur at specific sites within IgA1 hinge-region. We hy-pothesized that GalNAc-Ts play a role in the formation of gd-IgA1, due to their role in determining glycosylation sites and densities. To better understand how GalNAc-Ts may change O-glycans of IgA1 in IgAN we characterized the complex glycosylation mecha-nism involved in mucin-type O-glycan synthesis of IgA1 hinge-region. In the first section of this work, we explore …

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Protein O-Glcnacylation In Hippocampal Hyperexcitability & Gabaergic Neurotransmission, Luke Thomas Stewart Jan 2018

Protein O-Glcnacylation In Hippocampal Hyperexcitability & Gabaergic Neurotransmission, Luke Thomas Stewart

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Plasticity at central synapses is a vital component of neuronal function and an intensively studied phenomenon thought to underlie learning and memory processes in brain structures including the hippocampus and cerebral cortex. A principle mechanism at work during long-term plasticity is the rapid and heavily regulated post-translational modification of synaptic proteins such as phosphorylation and ubiquitination. A comparatively understudied modification is ‘O-GlcNAcylation’, a distinct form of monoglycosylation with rapid intracellular signaling capacity as opposed to the structural and extracellular signaling roles of O- and N-linked polysaccharide chains on conventionally glycosylated proteins. O-GlcNAcylated proteins are found in every cell type/tissue system …

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Pharmacological Inhibition Of Thioredoxin-Interacting Protein To Protect Against Diabetes, Lance Thielen Jan 2018

Pharmacological Inhibition Of Thioredoxin-Interacting Protein To Protect Against Diabetes, Lance Thielen

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The loss of functional beta cell mass represents a major factor in the pathogenesis of type 1 and type 2 diabetes. Inadequate production of insulin, a glucose-lowering hormone, and elevated glucagon production, a gluconeogenic hormone, contribute to impaired glycemic control and hyperglycemia. This promotes a vicious cycle involving glucotoxicity and additional beta cell dysfunction. Currently there are no therapies that halt this process; however, thioredoxin-interacting protein (TXNIP) has recently emerged as a promising therapeutic target. TXNIP was found to be the top glucose-induced gene in a human pancreatic islet microarray, is increased in mouse models of diabetes and diabetic human …

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The Effects Of Body Size, Growth, And History Of Diabetes On Glioma Risk, Rebecca Barnhill Little Jan 2018

The Effects Of Body Size, Growth, And History Of Diabetes On Glioma Risk, Rebecca Barnhill Little

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Many dietary exposures have weak or null associations with glioma risk. As nutrition can affect growth rate in adolescence, body size throughout the lifespan, and the propensity for Type 2 diabetes, the goal of this project was to examine the relationships between these surrogates of nutritional states and the risk of glioma. The aims of this project were to examine the associations between glioma risk and 1) self-reported body measures; 2) age when full height was attained; 3) and a history of diabetes. To investigate the first aim, 1,111 glioma cases and 1,096 community controls completed a structured interview to …

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Growth And Analysis Of Transition-Metal-Doped Znse-Based Materials And Thin Film Structures For Mid-Infrared Optoelectronic Applications, Zachary R. Lindsey Jan 2018

Growth And Analysis Of Transition-Metal-Doped Znse-Based Materials And Thin Film Structures For Mid-Infrared Optoelectronic Applications, Zachary R. Lindsey

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Transition metal (TM)-doped II-VI semiconductor thin films have been shown to be attractive materials for mid-infrared (mid-IR) laser sources due to broad applicability in the sensing and detection of a wide range of organic molecules. Specifically, when ZnSe is doped with Cr2+ ions, the resulting broadband emission characteristics in the 2-3 µm spectral range create the potential for tunable lasing in the mid-IR. This dissertation research is motivated by the need for low cost, efficient, portable materials to be incorporated into multilayered mid-IR optoelectronic devices providing appropriate optical confinement, efficient quantum confinement of carriers, and optical emission in the mid-IR …

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The Oxidative Tyrosine Modification, O,O’-Dityrosine, In Lung Disease, Morgan Locy Jan 2018

The Oxidative Tyrosine Modification, O,O’-Dityrosine, In Lung Disease, Morgan Locy

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The oxidative tyrosine modification, o,o′-dityrosine, has been identified in various pathologic conditions associated with oxidative stress in mammalian systems, and demonstrated to be important in physiologic processes in invertebrate organisms. The formation of o,o’-dityrosine is catalyzed by a heme peroxidase (hPx) in the presence of hydrogen peroxide (H2O2). The understanding of this stable, covalent tyrosine modifica-tion in lung biology is limited. Oxidative stress has been implicated in the pathogenesis of various lung diseases, including interstitial lung disease (ILD) and cystic fibrosis (CF). We observed that the oxidative protein modification, o,o’-dityrosine, was markedly ele-vated in the circulating plasma of ILD patients …

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Gender Differences In The Metabolism And Antidepressant Effects Of Ketamine, Emily Hugo Jan 2018

Gender Differences In The Metabolism And Antidepressant Effects Of Ketamine, Emily Hugo

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Ketamine is a dissociative anesthetic that interacts with the glutamatergic system, acting as an N-methyl-D-aspartate (NMDA) receptor antagonist. At higher doses, ketamine produces negative psychotomimetic side effects, including hallucinations and delirium, leading to its abuse in the 1980s and 90s. Recently, it has been determined that at sub-anesthetic doses, it is a fast-acting antidepressant. Because ketamine elicits fast and long-lasting antidepressant responses in patients, it is being studied as a possible treatment option for those with major depressive disorder and treatment-resistant depression. Further, studies have shown that men and women respond to ketamine treatments differently, especially in long-term treatment, suggesting …

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A Rare Case Of Primary Peritoneal Carcinoma With Atypical Presentation, Mohammed Abdulhaleem, Usman Zafar, Ali Hachem, Farrah Ibrahim Jan 2018

A Rare Case Of Primary Peritoneal Carcinoma With Atypical Presentation, Mohammed Abdulhaleem, Usman Zafar, Ali Hachem, Farrah Ibrahim

UAB Huntsville Research Day - All Presentations

2018 clinical vignette poster

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Infant Anorexia: A Case Study Of Oral Aversion Disorder, Jennie Stanford, Shivani Malhorta Jan 2018

Infant Anorexia: A Case Study Of Oral Aversion Disorder, Jennie Stanford, Shivani Malhorta

UAB Huntsville Research Day - All Presentations

2018 clinical vignette poster

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Preventing Osteoarthritis By Targeting The Transforming Growth Factor Beta Signaling Pathway, Robert Dalton Chavez Jan 2018

Preventing Osteoarthritis By Targeting The Transforming Growth Factor Beta Signaling Pathway, Robert Dalton Chavez

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Osteoarthritis (OA) is characterized by degenerated cartilage. In age-related OA, the molecular mechanisms that initiate cartilage erosion are not well defined. However, transforming growth factor beta (TGF-β) signaling is attenuated in the cartilage of patients with age-related OA and therefore may play a role in the disease. Degenerated cartilage has a rough surface and exhibits changes in stiffness. Proteoglycan 4 (PRG4), also known as lubricin, helps lubricate the surface of cartilage, and 3’-phosphoadenosine 5’-phosphosulfate synthase 2 (PAPSS2) helps maintain the stiffness of cartilage. Both PRG4 and PAPSS2 are regulated by TGF-β and down-regulated in OA cartilage. The present research elucidated …

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Characterization Of Membrane Associated Mucins In Ocular Surface Disease, Anna Ablamowicz Jan 2018

Characterization Of Membrane Associated Mucins In Ocular Surface Disease, Anna Ablamowicz

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Mucins on the ocular surface are found in the tear film and are attached to corneal and conjunctival epithelial cells on the eye. The bulbar conjunctiva of the ocular surface can be divided into four anatomical regions: temporal, superior, nasal, and inferior. The palpebral conjunctiva is the epithelial layer of the inner surfaces of the upper and lower eyelids. In the tears, mucins provide lubrication of the ocular surface through formation of a hydrophilic gel. The primary mucin in the tear film is MUC5AC which is secreted by goblet cells that are located in varying densities within the bulbar conjunctiva. …

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Parental Decision-Making In Use Of Complementary And Alternative Medicine, Meka B. Astin Jan 2018

Parental Decision-Making In Use Of Complementary And Alternative Medicine, Meka B. Astin

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One health care trend is the growing public interest in, and use of, complementary and alternative medicine (CAM). Research in the United States suggests that significant numbers of children are involved in various forms of alternative medicine. The purpose of this dissertation is to assess the predictors of parental decision-making of CAM use for their child using five categories of CAM therapies: alternative medical systems, biologically- based, mind-body, manipulative, and a separate and distinct category to include all CAM medical systems. Andersen’s health care Utilization Model (HUM), which holds that health service use is a function of predisposing, enabling, needs …

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A Study To Examine The Relationship Between Hospital Mergers And Patient Experience, Timothy William Attebery Jan 2018

A Study To Examine The Relationship Between Hospital Mergers And Patient Experience, Timothy William Attebery

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Since 2009, the United States has experienced another wave of hospital mergers. Consequently, health systems are getting larger and increasing their market concentration. How patients benefit from hospital consolidation remains an open issue for policy-makers, economists, health care executives, community leaders, politicians, government agencies, and others. One measure of healthcare consolidation’s impact, and its potential benefit/detriment, is how mergers affect patient experience, which, since 2007, has been measured by the standardized HCAHPS instrument. Hundreds of studies conducted over the past 50 years have found mergers trigger an internal, socially-disruptive effect in the first 12 to 24 months following the event …

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Examination Of The Dynamic Assembly Mechanism Of E. Coli Clpa, Elizabeth C. Duran Jan 2018

Examination Of The Dynamic Assembly Mechanism Of E. Coli Clpa, Elizabeth C. Duran

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E. coli ClpA is an AAA+ (ATPase Associated with diverse cellular Activities) chaperone that catalyzes the ATP-dependent unfolding and translocation of substrate proteins targeted for degradation into a protease, ClpP. ClpA, like many other AAA+ proteins, assembles into a hexameric ring competent for binding polypeptide substrate clients in the presence of ATP. Each ClpA protomer contains two nucleotide binding domains, NBD1 and NBD2. Recently, our lab applied hydrodynamic techniques to quantify the self-assembly mechanism of a closely related AAA+ chaperone, E. coli ClpB. Here we apply the techniques and analysis from that work to investigate the nucleotide-linked self-assembly mechanism of …

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Cerebral Vasospasm Detection And Treatment Using Transcranial Doppler Signal Analysis And Adaptive Medication Pump Mechanism, Khaled Elzaafarany Jan 2018

Cerebral Vasospasm Detection And Treatment Using Transcranial Doppler Signal Analysis And Adaptive Medication Pump Mechanism, Khaled Elzaafarany

All ETDs from UAB

In the United States, many patients pass away due to delayed detection of Cerebral Vasospasm (CV). Transcranial Doppler (TCD) is an efficient noninvasive, reliable device that can monitor the blood flow in various parts of the human brain like middle cerebral artery and basilar artery without any surgical intervention. It can help neurologists to diagnose many brain problems like edema, trauma, hemorrhage, and aneurysm. Unfortunately, continuous or even daily TCD monitoring is challenging due to the operator expertise and certification required in the form of a trained technologist, and certified physician to perform these studies. This barrier exists due to …

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Endodontic Post Retention With Resin Cements (Ilumi Fiber Post), Faimeena Farheen Jan 2018

Endodontic Post Retention With Resin Cements (Ilumi Fiber Post), Faimeena Farheen

All ETDs from UAB

Objectives: Loss of post retention is the leading cause in the cemented post. There is no good method of bonding a fiber post in a post space with resin cements because adhesive cementation into a prepared post space is difficult- due to an inability to place, dry and light cure the adhesive and the cement. A new post system (iLumi) that transmits light to the apex of the post has recently been developed. We want to know if this system will improve post retention in each section (coronal, middle and apical) of the prepared post space and if this curing …

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Membrane Capacitance Derived From Bioimpedance Spectroscopy Is Associated With Insulin Resistance In Relatively Healthy U.S. Women, But Not Men, Valene Garr Barry Jan 2018

Membrane Capacitance Derived From Bioimpedance Spectroscopy Is Associated With Insulin Resistance In Relatively Healthy U.S. Women, But Not Men, Valene Garr Barry

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Current screening methods have failed to detect more than 50% of the 120 million U.S. adults with insulin resistance and/or metabolic syndrome, conditions that substantially increase one’s risk for cardiometabolic disease (CMD).1 Evidence exists that metabolic health is associated with cell membrane composition, which is reflected in the electrical properties of the body cell mass. The objective of this study was to determine whether bioimpedance spectroscopy can identify insulin resistance and/or metabolic syndrome by evaluating membrane capacitance (CM). We hypothesized that CM would be higher in individuals with insulin resistance and/or metabolic syndrome when compared to healthy individuals. This cross-sectional …

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Effects Of Medicaid Expansion On The Financial Performance Of Rural Hospitals, Keith Darryl Brady Jan 2018

Effects Of Medicaid Expansion On The Financial Performance Of Rural Hospitals, Keith Darryl Brady

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EFFECTS OF MEDICAID EXPANSION ON THE FINANCIAL PERFORMANCE OF RURAL HOSPITALS KEITH BRADY DOCTOR OF SCIENCE IN HEALTH SERVICES ADMINISTRATION ABSTRACT The purpose of this research was to examine the effects of Medicaid expansion on the financial performance of rural hospitals. The analysis compares Medicaid revenue, uncompensated care cost and operating margins between rural hospitals in states that expanded Medicaid and rural hospitals in states that did not expand Medicaid. Strategic Management Theory was used to develop a theoretical framework to address three primary hypotheses. Secondary data from the Medicare Cost Report (MCR), the Agency for Healthcare Research and Quality …

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Nanomedicine: Electrohydrodynamic Atomization (Ehda) To Engineer Next-Generation Biomimetic Microphysiological Systems (Mps) And Precision Drug Delivery Systems (Dds), Karim Ismail Budhwani Jan 2018

Nanomedicine: Electrohydrodynamic Atomization (Ehda) To Engineer Next-Generation Biomimetic Microphysiological Systems (Mps) And Precision Drug Delivery Systems (Dds), Karim Ismail Budhwani

All ETDs from UAB

Cancer is poised to become the leading cause of death worldwide with lifetime probability of 1-in-2 men and 1-in-3 women developing cancer. Despite this, research and development of new treatment options remains expensive and slow, in part, due to inadequate disease models, therapy evaluation assays, and absence of delivery control in leading treatment options. These factors also impede patient-specific personalized medicine. Electrohydrodynamic atomization (EHDA) fabrication technologies, such as electrospinning (ESp) and electrospraying (ESy), offer promising nanomedicine pathways toward addressing these challenges. ESp has garnered much interest in tissue engineering but is dwarfed by softlithography in microphysiological systems (MPS), including lab-chip …

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Religiosity And Spirituality As Predictors Of Substance Use In Patients With Cystic Fibrosis, Benjamin Edwin Burgess Jan 2018

Religiosity And Spirituality As Predictors Of Substance Use In Patients With Cystic Fibrosis, Benjamin Edwin Burgess

All ETDs from UAB

Cystic fibrosis (CF) is a degenerative chronic illness that results in pulmonary and gastrointestinal impairment. Because health-related behaviors, such as substance use, impact health outcomes in this population, it is important to understand factors that predict substance use in patients with CF. Thus, this study aimed to examine the unique roles of spirituality and religiosity in alcohol, tobacco, and marijuana use. Higher religiosity was expected to predict lower substance use directly, reflecting a direct regulation of health behavior. Higher spirituality was expected to predict less substance use through lower depression, reflecting an indirect regulation of health behavior through emotion regulation. …

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Adiposity And Health In Zoo African And Asian Elephants, Daniella Chusyd Jan 2018

Adiposity And Health In Zoo African And Asian Elephants, Daniella Chusyd

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African (Loxodonta africana) and Asian (Elephas maximus) elephant populations are rapidly declining due to poaching, and habitat fragmentation and loss. Due to the precarious situation elephants are facing worldwide, captive elephant populations are being viewed as an insurance policy against extinction. Unfortunately, captive elephant populations are not self-sustaining, in part because of reproductive and health issues. One hypothesis for the observed reproductive and health issues is zoo elephants are obese. The current method of assessing obesity in elephants is based on a qualitative visual tool, the body condition score, which does not quantify fat mass. The purpose of this dissertation …

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Sleep Disturbances In Children With Autism Spectrum Disorder, Christian Clesi Jan 2018

Sleep Disturbances In Children With Autism Spectrum Disorder, Christian Clesi

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Autism Spectrum Disorder (ASD) is a neurodevelopmental disability characterized by impairments in social communication and restricted and repetitive patterns of behavior, interests, or activities (American Psychiatric Association, 2013). Children with autism may also have associated symptoms; one of the most prevalent being sleep disorders, with estimated prevalence rates ranging from 40 to 80% (Goldman, McGrew, Johnson, Richdale, Clemons, & Malow, 2011). Measuring sleep disturbances in this population can be particularly challenging due to the symptoms of the disorder, including impairments in communication. Therefore, research in this field regularly relies on parent-report data to measure sleep disturbances in children with ASD. …

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A Randomized Trial To Evaluate The Effect Of Allograft Bone Particle Size On Histomorphometric And Clinical Outcomes Following Ridge Augmentation Procedures, Hussein Basma Jan 2018

A Randomized Trial To Evaluate The Effect Of Allograft Bone Particle Size On Histomorphometric And Clinical Outcomes Following Ridge Augmentation Procedures, Hussein Basma

All ETDs from UAB

Ridge deficiency is an unfortunate obstacle that obviates the placement of dental implants or results in placing them at an angle that compromises the prosthetic restoration. An ideal volume is essential for implant placement in an optimal three-dimensional position. Several methods for augmenting the alveolar ridge in preparation for implant placement have been described. Autogenous bone grafts, considered to be the “gold standard”, are associated with significant morbidity and require a second surgical site. Guided bone regeneration (GBR), is an alternative technique that use bone-substitute materials as adjuncts to or replacements for autografts in bone augmentation procedures to overcome the …

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Evaluating The Biology And Ecology Of Sea Turtles In The Context Of Anthropogenic Climate Change, Elizabeth Michelle Bevan Jan 2018

Evaluating The Biology And Ecology Of Sea Turtles In The Context Of Anthropogenic Climate Change, Elizabeth Michelle Bevan

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This dissertation addresses several key gaps in our knowledge of how long-term threats, like climate change, impact the survival and reproduction of thermally-sensitive endangered sea turtles. Many aspects of the sea turtle life history, such as sex determination in hatchlings, are directly affected by environmental temperatures, making sea turtles crucial sentinels for monitoring the impacts of ecosystem variability. Chapter 1 re-evaluates the historic size of the Kemp’s ridley sea turtle population in the context of current nesting trends at its primary nesting habitat in the western Gulf of Mexico to address recovery targets and the conservation status for this species. …

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Functional Analysis Of Cdc45 In The Replication Fork And In Response To Replicative Stress, Amanda Debrot Jan 2018

Functional Analysis Of Cdc45 In The Replication Fork And In Response To Replicative Stress, Amanda Debrot

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DNA replication is a highly conserved and tightly regulated process, with a variety of factors acting to ensure faithful duplication and stability of chromosomal DNA. During replication, positive supercoils form ahead of the advancing replication fork. DNA topoisomerase 1 (Top1) acts to prevent DNA damage by relieving the torsional strain created by these supercoils. The camptothecin (CPT) class of chemotherapeutics target Top1, creating a long-lived DNA-Top1-CPT covalent complex, which leads to S-phase specific DNA lesions and cellular death. Our lab previously performed a genetic screen to isolate mutant proteins that enhance cell sensitivity to Top1-mediated DNA damage. One of the …

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The Influence Of Perceived Stress And Sleep Disturbance On Fatigue And Blood Pressure As Mediated By Cortisol In Children With Sickle Cell Disease, Heather Carol Soistmann Jan 2018

The Influence Of Perceived Stress And Sleep Disturbance On Fatigue And Blood Pressure As Mediated By Cortisol In Children With Sickle Cell Disease, Heather Carol Soistmann

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ABSTRACT Introduction: Life expectancy is improving for those with sickle cell disease (SCD); however, with this improvement come increasing risks for long-term health complications. Early identification of health concerns could lead to improved long-term health outcomes. Two health concerns in school-age children with SCD are fatigue and blood pressure (BP). Previous research with other populations indicates perceived stress and sleep disturbance may influence outcomes of fatigue and BP. Further, cortisol, a stress hormone, may mediate the proposed relationships. Therefore, the purpose of the study was to determine effect sizes of relationships between fatigue, BP, perceived stress, and sleep disturbance in …

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The Primary Cilium Regulates Interstitial Immune Cells During Renal Cystogenesis, Cheng Song Jan 2018

The Primary Cilium Regulates Interstitial Immune Cells During Renal Cystogenesis, Cheng Song

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Renal cysts are a pathological condition that can lead to end-stage renal failure and death. The mechanisms that underlie renal cyst development are under active investigation, and emerging evidence has revealed defects in a number of proteins required for cilia assembly or signaling, such as intraflagellar transport (IFT) proteins and the polycystins. Characterization of mice harboring conditional IFT mutations suggests that the rate of cyst formation is dependent upon the timing of cilia loss. Induction of cilia loss in juvenile mice results in rapid cyst development, while induction of cilia loss in adult mice leads to a slower progressing form …

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Understanding Associations Among Race, Socioeconomic Status, And The Experience Of Painful Knee Osteoarthritis: Clinical And Experimental Evidence, Kathryn Ann Thompson Jan 2018

Understanding Associations Among Race, Socioeconomic Status, And The Experience Of Painful Knee Osteoarthritis: Clinical And Experimental Evidence, Kathryn Ann Thompson

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Knee OA is an active disease process involving cartilage destruction, subchondral bone thickening, and new bone formation affecting 22% of American adults (46.4 million) over age 18 years. Past literature suggests, a disproportionate number of racial/ethnic minorities, particularly non-Hispanic Blacks, are affected by knee OA. Furthermore, over one in four (28%) Blacks have an income below the national poverty level compared with 11% of Whites. Therefore, the overall aim of this study is to examine racial and SES differences in the experience of pain and physical functioning in adults with knee OA. 191 participants (62% female, 52% Black) were recruited …

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Analysis Of The Gtp Cyclohydrolase I/Tetrahydrobiopterin Pathway In Glioblastoma Biology, Anh Tran Jan 2018

Analysis Of The Gtp Cyclohydrolase I/Tetrahydrobiopterin Pathway In Glioblastoma Biology, Anh Tran

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Glioblastomas (GBMs) are the most common primary malignant brain tumors in adults and one of the most aggressive cancers with high rates of recurrence and therapeutic resistance. In GBMs, subpopulations of highly tumorigenic cells called brain tumor initiating cells (BTICs) have the unique capacity to promote tumor maintenance, therapeutic resistance, and angiogenesis. Depending on the level, differentiation state, and tumor stage, reactive nitrogen and oxygen species inhibit or increase cancer growth and BTIC maintenance. GTP cyclohydrolase 1 (GCH1) is the rate limiting enzyme in a pathway that can regulate reactive species production but has not been thoroughly investigated in GBM. …

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