Medicine and Health Sciences Commons^™

The Multifactorial Roles Of The Cytokines Il-21 And Il-22 In Mediating Host Defense Against Enteropathogenic Infection, Daniel James Silberger

All ETDs from UAB

Enteropathogenic strains of Escherichia coli are a major public health concern, causing diarrhea and mortality particularly among infants and children in developing countries. Citrobacter rodentium is a murine intestinal pathogen that models pathogenic E. coli infection. Both innate and adaptive immune cells contribute to the clearance of C. rodentium. In particular, B cells and CD4+ T cells but not CD8+ T cells are required for protection during a primary infection with C. rodentium. In addition, T cell-dependent antibody responses are required for clearance. Th17 cells are a major CD4+ T cell population that accumulates in the large intestine during C. …

Exploiting The Glioblastoma Tumor Microenvironment For Enhanced Oncolytic Herpes Simplex Virus Therapy, Tyrel Talbert Smith

All ETDs from UAB

Gliomas are the most common and fatal malignancy of the adult central nervous system. The need for new therapeutic options is clear, as standard of care therapies only extend median survival 12-14 months beyond diagnosis. Conditionally replication-competent oncolytic herpes simplex type-1 viruses (oHSV) have emerged as promising therapeutics for treating malignant gliomas. However, two factors that contribute to the dismal prognosis of malignant gliomas, immunosuppression and invasive growth, are also thought to limit virotherapeutic efficacy. We examined these factors in tumor microenvironments to explore novel strategies to treat malignant gliomas with oHSV for improved therapeutic response. In a Phase 1b …

Acceptance And Uptake Of Influenza Vaccination By Health Care Workers, Leshonda Wallace

Walden Dissertations and Doctoral Studies

Influenza is a preventable infectious disease, against which vaccination is the primary means of protection. Health care workers (HCW) are among the most vulnerable to the illness and are likely to be sources of infection transmission while caring for patients. Circumstantial evidence suggests higher rates of vaccination coverage by HCW will coincide with a lower incidence of influenza transmission, yet a gap remains in the literature regarding governing health agencies' (i.e., licensing boards, medical and nursing associations) influence on the influenza vaccination practices of their constituents. Moreover, discrepancies exist between governing health agencies' and the National Vaccine Advisory Committee's recommendations …

Decoding Nf1 Intragenic Copy-Number Changes, Meng-Chang Hsiao

All ETDs from UAB

Genomic rearrangements may cause both Mendelian and complex disorders. Currently, several major mechanisms causing genomic rearrangements have been proposed such as non-allelic homologous recombination (NAHR), non-homologous end joining (NHEJ), fork stalling and template switching (FoSTeS) and microhomology-mediated break-induced replication (MMBIR). However, to what extent these mechanisms contribute to gene-specific pathogenic copy-number changes (CNCs) remains understudied. Furthermore, only few studies resolved these pathogenic alterations at the nucleotide-level. Accordingly, our aim was to explore which mechanisms contribute to a large, unique set of locus-specific non-recurrent genomic rearrangements causing the genetic neurocutaneous disorder neurofibromatosis type 1 (NF1). Through breakpoint-spanning PCR as well as …

Energy Metabolism Of Platelets During Activation, Oxidative Stress And Storage, Saranya Ravi

All ETDs from UAB

The principal function of platelets is to regulate hemostasis, and dysfunction of platelet aggregation or activation can lead to either excessive thrombotic or hemorrhagic complications. It has been shown that the ability to generate ATP and exposure to oxidative stress can affect platelet thrombotic potential. While platelet metabolism has been extensively studied, the importance of substrate availability and metabolic plasticity in regulating aggregation under physiological or pathological conditions is not well understood. In this dissertation, we examined the reliance of platelets on different metabolic substrates, the importance of ATP production for aggregation in response to thrombin stimulation, metabolic stress following …

Role Of Vapb/Als8 Signaling Through Lar Receptor, Jessica Lindsey Winek Schultz

All ETDs from UAB

In humans, a P56S point mutation in the VAPB/ALS8 MSP domain is associated with amyotrophic lateral sclerosis (ALS) and late-onset spinal muscular atrophy (SMA). The N-terminal MSP domain is cleaved from the C-terminus, and secreted through an unknown, nonconventional manner. The P56S mutation inhibits secretion of the MSP domain. We use Caenorhabditis elegans to study live secretion of VPR-1, as well as to understand vMSP receptor signaling in muscle and gonad. To study the secretion mechanism of VPR-1 we created a transgenic line of C. elegans with a fluorescently tagged VPR-1. Using this model, we were able to visualize live …

Children With Sli Exhibit Delays Resolving Ambiguous Reference, Julie M. Estis, Brenda L. Beverly

University Faculty and Staff Publications

Fast mapping weaknesses in children with specific language impairment (SLI) may be explained by differences in disambiguation, mapping an unknown word to an unnamed object. The impact of language ability and linguistic stimulus on disambiguation was investigated. Sixteen children with SLI (8 preschool, 8 school-age) and sixteen typically developing age-matched children selected referents given familiar and unfamiliar object pairs in three ambiguous conditions: phonologically distinct word (PD), phonologically similar word (PS), no word (NW). Preschoolers with SLI did not disambiguate, unlike typically developing age-matched participants, who consistently selected unfamiliar objects given PD. School-age children with SLI disambiguated given PD. Delays …

Development Of An Avian Model For Identifying Individual Differences In Drug Vulnerability, Beth A. Rice

Theses and Dissertations--Psychology

The attribution of incentive salience to cues that become associated with drugs of abuse is a critical characteristic of individuals who may be vulnerable to drug addiction. Rodents with the propensity to sign track are thought to be vulnerable to drug abuse. The goal of the current work was to investigate whether sign trackers (STs) would acquire cocaine conditioned place preference (CPP) to a discrete cue using an avian species. In Experiment 1, sign and goal trackers (GTs) were first identified using a one third rank order split. Following identification, cocaine-CPP was conducted with a discrete cue in each end …

Effects Of Brain-Derived Neurotrophic Factor And Its Signaling Pathway On Sensory Neuronal Activation During Colitis, Fiza Hashmi

Theses and Dissertations

Visceral hypersensitivity is the heightened response to sensory stimuli. Visceral sensations are transmitted through primary afferent neurons in the dorsal root ganglion (DRG) and the sensitization of the neural pathway leads to modification in spinal ascending and descending neurons. The aim of this investigation is to determine the effects of brain-derived neurotrophic factor (BDNF) and its signaling pathway on sensory neuronal activation during colitis. In order to evaluate this, levels of calcitonin-gene related peptide (CGRP), a neuropeptide marker for nociceptive transmission, and phosphorylated cAMP-response element binding protein (pCREB), a molecular switch in neuronal plasticity, were studied in response to BDNF …

Effects Of Hiv-1 Viral Protein Tat On The Viability And Function Of Oligodendroglial Cells, Shiping Zou

Theses and Dissertations

Myelin pallor is frequently reported in HIV patients, and can occur in the CNS prior to other evidence of disease process. Our exploratory studies showed that oligodendrocytes (OLs) are direct targets of HIV-1 Tat (transactivator of transcription). Tat induces a dose-dependent increase of intracellular Ca²⁺ level ([Ca²⁺]_i) in cultured murine OLs, which can be attenuated by ionotropic glutamate receptor (iGluR) antagonists MK801 and CNQX. The Tat-induced [Ca²⁺]_i increase leads to increased death in immature (O4⁺, MBP^-), but not mature (O4⁺, MBP⁺) OLs, over 96 …

Meta-Analysis Of Gene Expression Studies, Umaporn Siangphoe

Theses and Dissertations

Combining effect sizes from individual studies using random-effects models are commonly applied in high-dimensional gene expression data. However, unknown study heterogeneity can arise from inconsistency of sample qualities and experimental conditions. High heterogeneity of effect sizes can reduce statistical power of the models. We proposed two new methods for random effects estimation and measurements for model variation and strength of the study heterogeneity. We then developed a statistical technique to test for significance of random effects and identify heterogeneous genes. We also proposed another meta-analytic approach that incorporates informative weights in the random effects meta-analysis models. We compared the proposed …

Interaction Between Atm Kinase And P53 In Determining Glioma Radiosensitivity, Syed F. Ahmad

Theses and Dissertations

Glioblastoma multiforme (GBM) is the most common primary brain tumor. Studies have shown that targeting the DNA damage response can sensitize cancer cells to DNA damaging agents. Ataxia telangiectasia mutated (ATM) is involved in signaling DNA double strand breaks. Our group has previously shown that ATM inhibitors (ATMi) sensitize GBM cells and tumors to ionizing radiation. This effect is greater when the tumor suppressor p53 is mutated.

The goals of this work include validation of a new ATM inhibitor, AZ32, and elucidation of how ATMi and p53 status interact to promote cell death after radiation. We propose that ATMi and …

Measuring The Impact Of Recognized Patient-Centered Medical Homes (Pcmh), Rick Moore

Theses and Dissertations

This dissertation proposal seeks to understand if the increasingnumbers (density) of recognized PCMH practices incommunities affect avoidable hospitalizations related toambulatory care sensitive conditions (ACSC), as measured bythe AHRQ Composite Prevention Quality Indicators (PQI). Theresearch has two purposes: 1. Establish constructs and hypotheses to measurethe effect of the increasing numbers of NCQA-Recognized PCMH practices in communities(counties). 2. Using an outcomes-based measurement approach,investigate the relationship between growingdensities of NCQA-Recognized PCMH practicedoctors among all primary care doctors (PCD) ina community and the associated impact on theutilization of inpatient care, specifically related toACSCs, as measured by the AHRQ CompositePQIs.

The research is quasi-experimental in …

Conduction States Of The Human Dopamine Transporter, Krasnodara Cameron

Theses and Dissertations

Dysregulation of dopaminergic homeostasis has been established as the primary source of numerous neurological disorders including Parkinson’s and drug addiction. A tonic increase of dopamine (DA) in the nucleus accumbens is required for associating everyday events and behaviors with rewards. Yet many addictive exogenous compounds such as amphetamine (AMPH) and cocaine (COC) produce a much greater augmentation of synaptic DA levels that are linked to euphoria and a shift in behavior towards drug seeking. The protein responsible for maintaining extracellular levels of DA is the dopamine transporter (DAT). It is primarily located in the perisynaptic area at terminals of pre-synaptic …

Incorporation Of Molecular Diagnostics Into Medical Laboratory Science Curriculum: Clinical Facilities Expectations. An Asynchronous, Iterative, Online Delphi Study., Barbara Kraj

Theses and Dissertations

The medical laboratory science (MLS) profession is in need for published molecular diagnostics competency-based standards and curriculum. To assess their expectations of new MLS graduates, professionals performing and supervising performance of clinical molecular assays were surveyed to rate the importance of relevant cognitive and psychomotor learning objectives. A modified, asynchronous, iterative online Delphi process was utilized for assessment of consensus on the importance of the objectives. The survey was delivered through online REDCap application. Program directors of 221 MLS programs accredited by the National Accrediting Agency for Clinical Laboratory Science (NAACLS) were asked to forward the first Delphi survey to …

Effects Of Hiv-1 Tat On The Enteric Nervous, Joy Ngwainmbi

Theses and Dissertations

More than 1.2 million people are estimated to be currently living with the human immunodeficiency virus (HIV) in the United States of America. The gastrointestinal (GI) tract is both a major target and an important component of HIV pathogenesis. The GI processes that are dysregulated during HIV infection are controlled by the enteric nervous system (ENS). Indeed, both clinical and experimental studies have implicated the ENS in HIV and simian immunodeficiency virus (SIV) pathogenesis. In addition to direct viral effects, the HIV virus also indirectly affects the GI tract via cellular and/or viral toxins released by infected cells. Trans-activator of …

Dual Pi3k/Mtor Inhibition With Bez235 Augments The Therapeutic Efficacy Of Doxorubicin In Cancer Without Influencing Cardiac Function, David E. Durrant

Theses and Dissertations

Cancer continues to be a leading cause death in the United States despite improved treatments. Cancerous lesions form after acquiring oncogenic driver mutations or losing tumor suppressor function in normal cells. Traditional therapies have included use of genotoxic substances that take advantage of the increased growth rate and loss of tumor suppressor function to cause cell death. One such drug is the anthracycline antibiotic doxorubicin (DOX). DOX interchelates into DNA and disrupts transcriptional machinery while also poisoning topoisomerase II. This results in single and double stranded DNA breaks, which if severe enough leads to either necrotic or apoptotic cell death. …

Investigating The Role Of Bptf In Immunoediting In Breast Cancer And Melanoma, Kristen N. Peterson

Theses and Dissertations

In this study, we explore the effects of NURF depletion on the growth of tumors in immune-competent mice. NURF depletion in tumors results in reduced tumor growth in immune-competent mice, suggesting enhanced anti-tumor immunity. Analysis of the tumor microenvironment by flow cytometry revealed a significantly elevated CD8 and progressively elevated activated CD8 phenotype in Bptf KD tumors, possibly contributing to the increase in cell death and decrease in tumor weight observed. Examination of antigen presentation was evaluated using the OT-1 and Pmel-17 models, though no significant difference in cytotoxicity was observed as measured by LDH and/or IFNγ assays. This indicates …

Inhibition Of Mtor Signaling Protects Against Myocardial Reperfusion Injury, Acute Myocardial Infarction, Scott M. Filippone

Theses and Dissertations

Acute myocardial infarction (AMI) is the leading cause of death worldwide. Currently, the best method of treating cardiac ischemia is early reperfusion which, itself, induces myocardial damage. The mTOR complex is a key regulator of cardioprotection against cell stressors. We hypothesized that reperfusion therapy with Rapamycin, a potent mTOR inhibitor, would reduce infarct size in adult mouse hearts. Rapamycin was administered at the onset of reperfusion following 30 min in situ LAD ligation. After 24 hours of reperfusion, myocardial infarct size and apoptosis were significantly reduced in rapamycin-treated mice compared to control. Rapamycin inhibited pro-apoptotic protein Bax and phosphorylation of …

The Impact Of One Fraction Of 8 Gy Radiotherapy In Palliative Treatmentof Multiple Myeloma Patients With Painful Bone Destructions, Milda Rudzianskiene, Arturas Inciura, Elona Juozaityte, Rolandas Gerbutavicius, Renata Simoliuniene, Viktoras Rudzianskas, Greta Emilia Kiavialaitis

Turkish Journal of Medical Sciences

Background/aim: Radiotherapy is required to overcome pain and to promote recalcification in multiple myeloma (MM) patients. The aim of our prospective study was to evaluate the impact of one fraction of 8 Gy regimen in palliative treatment of MM. Materials and methods: Forty-six patients with MM and painful bone destructions were treated by 8 Gy single fraction regimen. The visual analog scale was used for evaluation of pain. Analgesic use was measured prior to and after radiotherapy (4, 12, and 24 weeks). Recalcification was evaluated with radiographs before and after radiotherapy at 1 and 3 months. Quality of life questionnaires …

Hypolipidemic Effects Of Nimesulide And Celecoxib In Experimentally Induced Hypercholesterolemia In Rabbits, Sagheer Ahmed, Saima Gul, Muhammad Zia-Ul-Haq, Muhammad Riaz

Turkish Journal of Medical Sciences

Hypercholesterolemia plays an important role in the development of atherosclerotic disease, which is one of the leading causes of mortality in the world. Previous studies showed that cyclooxygenase (COX) inhibitors could be used in treating hypercholesterolemia. The present study was designed to test whether COX-2 inhibition can improve lipid profiles in hypercholesterolemia. Materials and methods: Rabbits were fed a high-cholesterol diet to produce hypercholesterolemia. The role of COX-2 was evaluated using celecoxib and nimesulide. Rabbits were divided into 4 groups: the first with normal healthy rabbits, second with high-cholesterol diet and pretreatment with saline, third with high-cholesterol diet and pretreatment …

Selenium Status In Blood, Urine, And Hair Samples Of Newly Diagnosed Pediatric Cancer Patients, Serap Karaman, Banu Mansuroğlu, Kadri̇ye Kizilbey, Serap Derman, Afi̇fe Bi̇nnaz Hazar

Turkish Journal of Medical Sciences

Background/aim: Selenium (Se) is a trace element that has multiple functions. Low Se amounts in serum and hair have been reported in pediatric and adult cancer patients. The aim of our study was to evaluate Se levels in the serum, urine, and hair of pediatric cancer patients with leukemia, lymphoma, and solid tumors when compared with healthy children. Materials and methods: The concentrations of Se in the serum, hair, and urine of 32 Turkish children as healthy controls and 88 Turkish children diagnosed with acute leukemia (58), lymphoma (16), and solid tumors (14) were measured using inductively coupled plasma mass …

The Effects Of Prenatal Long-Duration Exposure To 900-Mhz Electromagnetic Field On The 21-Day-Old Newborn Male Rat Liver, Zehra Topal, Hati̇ce Hanci, Tolga Mercantepe, Hüseyi̇n Serkan Erol, Osman Nuri̇ Keleş, Haydar Kaya, Sevdegül Mungan, Ersan Odaci

Turkish Journal of Medical Sciences

Background/aim: To determine what effect a 900-MHz electromagnetic field (EMF) applied in the prenatal period would have on the liver in the postnatal period. Materials and methods: At the start of the study, adult pregnant rats were divided into two groups, control and experimental. The experimental group was exposed to a 900-MHz EMF for 1 h daily during days 13?21 of pregnancy. After birth, no procedure was performed on either mothers or pups. Male rat pups (n = 6) from the control group mothers (CGMR) and male rat pups (n = 6) from the experimental group mothers (EGMR) were sacrificed …

Sigma Receptor Activation Mitigates Toxicity Evoked By The Convergence Of Ischemia, Acidosis And Amyloid-Beta, Adam Alexander Behensky

USF Tampa Graduate Theses and Dissertations

Stroke is the fifth leading cause of death in the United States and a major cause of long-term disability in industrialized countries. The core region of an ischemic stroke dies within minutes due to activation of necrotic pathways. Outside of this core region is the penumbral zone, where some perfusion is maintained via collateral arteries. Delayed cell death occurs in this area due to the triggering of apoptotic mechanisms, which expands the ischemic injury over time. The cellular and molecular events that produce the expansion of the ischemic core continue to be poorly understood. The increases in the amyloid precursor …

Neuroinflammatory Alterations Via Cd-36 In Traumatic Brain Injury, Diana G. Hernandez-Ontiveros

USF Tampa Graduate Theses and Dissertations

Traumatic brain injury (TBI) has become an increasingly unmet clinical need due to intense military conflicts worldwide. Directly impacted brain cells suffer massive death, with neighboring cells succumbing to progressive neurodegeneration accompanied by inflammatory and other secondary cell death events. Subsequent neurodegenerative events may extend to normal areas beyond the core of injury, thereby exacerbating the central nervous system’s inflammatory response to TBI. Recently CD-36 (cluster of differentiation 36/fatty acid translocase (FAT), a class B scavenger receptor of modified low-density lipoproteins (mLDLs) in macrophages, has been implicated in lipid metabolism, atherosclerosis, oxidative stress, and tissue injury in cerebral ischemia, and …

Altered Intraerythrocytic Development Phenotypes Of Artemisinin-Resistant Plasmodium Falciparum Confer A Fitness Advantage, Amanda Hott

USF Tampa Graduate Theses and Dissertations

Resistance to artemisinin combination therapies (ACTs) has emerged in southeast Asia threatening the most widely used treatment against antimalarial-resistant Plasmodium falciparum worldwide. Artemisinin resistance has been associated with a reduced rate of parasite clearance following treatment with an ACT and is attributed to increased survival of ring-stage parasites. Single nucleotide polymorphisms (SNPs) in kelch gene (K13) has been associated with delayed in vivo clearance half-life of artemisinin-resistant P. falciparum and is the only known molecular marker of resistance. The absence of reliable in vitro phenotypes for artemisinin resistance has limited our understanding of the resistance mechanism(s) and fitness costs, therefore …

Attentional Allocation In Language Processing In Adults Who Stutter: Erp Evidence, Wendy Lorraine Olsen

USF Tampa Graduate Theses and Dissertations

The aim of this study was to investigate how young adults who stutterer allocate attentional resources during two linguistic stages in picture naming, specifically lemma and lexeme retrieval. This study reports on behavioral and brain electrophysiological data collected during a simple auditory oddball task and a Dual Picture-Word Interference/Tone Monitoring Task.

Ikaros Deficiency Leads To An Imbalance In Effector And Regulatory T Cell Homeostasis In Murine Pancreatic Cancer, Nadine D. Nelson

USF Tampa Graduate Theses and Dissertations

Pancreatic cancer is one of the deadliest cancers with a five-year survival rate of 6%. Pancreatic cancer is resistant to conventional chemotherapy and is usually diagnosed at late stages. Current treatment options have minimal effects in extending patients' lives beyond 10 months. One significant limitation in developing treatments to combat pancreatic cancer is its immunosuppressive microenvironment. Pancreatic cancer secretes factors that activate immunosuppressive cells, such as regulatory T cells (Tregs). These Tregs suppress effector CD4⁺ and CD8⁺ T cell anti-tumor immune responses. Therefore, novel treatment options to reduce Treg-mediated immune suppression and increase the numbers and functions of …

Utilization Of Placebo Response In Double-Blind Psychopharmacological Studies, Contextual Perspective, Margarita Olegovna Ashirova

Antioch University Dissertations & Theses

Placebo response has been an elusive phenomenon in the fields of medicine, medical research, and psychology. Even though it has been heavily utilized as a comparator treatment in double-blind psychopharmacological studies, the reliable definition and consistent understanding of placebo response are missing. In this contextual exploration, I outlined the state of current placebo response research and variable rates of placebo response reported in double-blind studies. I identified the gap in the literature—lack of consistent understanding of placebo response—that has led to a waste of resources by the psychopharmacological research industry. Further, I compared and contrasted the current inconsistent Western medical …

History Of Concussion And Current Functional Movement Screen Scores In A Collegiate Recreational Population, Jordan M. Dorrien

College of Graduate Studies: Theses & Dissertations

Introduction: 1.6-3.8 million concussions occur annually related to sport.¹ Although neurometabolic alterations in the brain last 7-10 days following a concussion, an increased Cortical Silent Period (CSP) has been found to persist after 19 months.^2,3 Further, movement impairments have been noted years after injury.⁴ The Functional Movement Screen (FMS) assesses mobility and stability in the body.⁵ The purpose of this study was to assess if FMS scores correlate to history of a concussion in healthy college club sport participants. Methods: Health history and FMS score were collected on 55 participants (38 male, …