Medicine and Health Sciences Commons^™

Effects Of A Text Message-Based Motivational Interviewing Intervention On Cigarette Smoking In College Students., Anna Jorayeva

Electronic Theses and Dissertations

Purpose: The purpose of this dissertation was to examine the effects of a novel text message-based motivational interviewing intervention on cigarette smoking behavior in college students. Three manuscripts comprised this dissertation and included: a state of the science review of motivational interviewing and text message-based smoking behavior interventions in adolescents and young adults; a critical review and analysis of instruments used to measure nicotine dependence in young adults; and a quasi-experimental study testing the effects of a novel text message-based motivational interviewing intervention on cigarette smoking behavior in college students. Background: Cigarette smoking is the number one preventable cause of …

Pro-Inflammatory Cytokines Promote Viral Replication And Cell Cycle Mediators In Arenavirus-Induced Hepatitis., Gretchen E. Holz

Electronic Theses and Dissertations

Lassa virus (LASV) is an arenavirus and causative agent of Lassa fever (LF), a viral hemorrhagic fever in West Africa for which there is no vaccine. Lymphocytic choriomeningitis virus (LCMV), is used as a surrogate to mimic LASV-induced liver pathology. LCMV-WE, not LCMV-ARM, causes disease in primates and mice characterized by hepatitis, high viral load, hepatocyte proliferation, and upregulated proliferative triggers (e.g. TNF-α, IL-6 ). We hypothesize LCMV-WE induces pathological hepatocyte proliferation via pro-inflammatory triggers (TNF-α, IL-6) from macrophages, leading to: increased viral replication, modulated cell cycle, and arrested cell cycle. RAW 264.7 macrophages and AML-12 hepatocytes, were used as …

The Role And Regulation Of Inhibitor Of Kappa B Kinase In The Impaired Monocyte Response., Norman James Galbraith

Electronic Theses and Dissertations

Trauma, major surgery and systemic infection can lead to a subsequent immunosuppressed state which can predispose patients to nosocomial infection and death. Approximately a sixth of patients will have impaired monocyte function, as determined by decreased HLA-DR expression or decreased TNF-α production in response to ex-vivo lipopolysaccharide (LPS) stimulation. This project aimed to develop an in-vitro model of impaired monocyte function using isolated monocytes from healthy volunteers, to study the effect of monocyte impairment on IκK signaling, and determine the role of IκK in the impaired monocyte response. These studies have provided the following results:

1. Monocytes treated with low dose …

The Role Of The Mir-200 Family On The Tumor Suppressor Rassf2 And The Effect On Mapk Pathway Activity In Colorectal Cancer., Jane V. Carter

Electronic Theses and Dissertations

This dissertation investigated the role of the miR-200 family in normal colon epithelial (CCD 841) and Dukes’ C (HT-29) colorectal cancer (CRC) cell lines. Our aim was to characterize expression of the miR-200 family (miR-200a, miR-200b, miR-200c, miR-141, and miR-429) in colorectal cell lines, study their effect on the tumor suppressor Ras Associated Domain-Containing Protein (RASSF) 2 and on subsequent activity within the mitogen-activated protein kinase (MAPK) signaling pathway. We wanted to determine whether regulation of miR-200 family members could change cell behavior towards more “cancer-like” in a normal colon epithelium (CCD 841) cell line, or less “cancer-like” in a …

The Impact Of Paroxysmal Sympathetic Hyperactivity Following Traumatic Brain Injury On Intensive Care Unit Length Of Stay And Discharge Disposition., Kimberly S. Meyer

Electronic Theses and Dissertations

Paroxysmal Sympathetic Hyperactivity (PSH) is a complication affecting a subset of patients with severe traumatic brain injury (TBI). It is associated with increased morbidity, longer lengths of stay, and delayed recovery (Perkes, Baguley, Nott, & Menon, 2010). The most prevalent signs and symptoms of PSH include unprovoked tachycardia, tachypnea, hypertension, dystonia, and diaphoresis (Lemke, 2007). If untreated, PSH can lead to impaired cerebral blood flow, sub-endocardial damage, dehydration, malnourishment, and contractures (Lemke, 2007). Results from this retrospective study indicate that there is no difference in intensive unit (ICU) length of stay in TBI patients with PSH compared to those without …

Mechanism Of Interaction Of Peptide Modified Nanoparticles With Porphyromonas Gingivalis., Ankita Jain

Electronic Theses and Dissertations

Studies suggest that P. gingivalis functions as a keystone pathogen and interacts with primary colonizers in the supragingival biofilm such as S. gordonii. This interaction contributes to the initial colonization of the oral cavity by P. gingivalis and thus represents a potential target for therapeutic intervention. We have identified a peptide (BAR) derived from the streptococcal SspB protein that functions to inhibit P. gingivalis adherence to S. gordonii. In addition, we showed that nanoparticles (NPs) functionalized with BAR inhibit this interaction more potently than free soluble peptide, possibly by promoting interaction with P. gingivalis at higher valency than …

Cost Of Care For Hospitalized Patients With Pulmonary Mycobacterial Diseases In The United States., Mary Beth Wells Allen

Electronic Theses and Dissertations

Background: Pulmonary mycobacterial diseases describe both tuberculosis (TB) and nontuberculous mycobacteria (NTM). Few data are available measuring the cost burden of mycobacterial diseases on the national level. The purpose of this study was to evaluate the cost burden and measure emerging trends in hospitalization of pulmonary TB and NTM in the US from 2001 through 2012. Methods: This study was a retrospective community based cost analysis of hospitalized patients with a principal diagnosis of pulmonary mycobacterial diseases from 2001 through 2012. Data for pulmonary TB and NTM were retrieved from the Healthcare Cost and Utilization Project (HCUP), US Department of …

Evaluating Cardiovascular Dysfunction During Increased Activity And Exercise Rehabilitation Following Incomplete Thoracic Spinal Cord Injury In The Adult Rat., Kathryn A. Harman

Electronic Theses and Dissertations

Spinal cord injury (SCI) results in whole-body dysfunction. While the majority of SCI research is focused on improving locomotor function after injury, cardiovascular (CV) disease continues to be the leading cause of morbidity in the chronic SCI patient population. The combination of injury-induced destruction of autonomic pathways, maladaptive plasticity within lumbosacral circuits, and the progressive decline in physical fitness contribute to the poor CV status of SCI individuals. Currently, there is little emphasis on implementing appropriately-timed acute rehabilitation techniques aimed to curtail maladaptive remodeling and improve CV outcomes. Furthermore, no pre-clinical or clinical studies have investigated the most appropriate time-course …

The Role Of Nicotine, A7 Nicotinic Acetylcholine Receptors And Extracellular Matrix Remodeling In Pulmonary Fibrosis., Glenn Ward Vicary

Electronic Theses and Dissertations

The median survival for idiopathic pulmonary fibrosis (IPF) patients from diagnosis is a dismal 3 years. This condition is characterized by pulmonary fibroproliferation and excess production and disordered deposition of extracellular matrix (ECM) proteins resulting in obliteration of the original tissue architecture, loss of lung function and eventual death due to respiratory failure. The main hindrance to the development of effective treatments against pulmonary fibrosis is the late detection of its progression and is often of unknown cause. Tobacco smoke represents the most important environmental factor linked to the development of pulmonary fibrosis, with over 60% of IPF patients current …

The Effects Of Direct Peritoneal Resuscitation On Leukocyte Infiltration After Acute Brain Death., Jessica Lee Weaver

Electronic Theses and Dissertations

Background: Brain death triggers an inflammatory response that is associated with worse outcomes for recipients of transplanted organs procured from brain dead donors. The intestine has been shown to release inflammatory mediators in other types of shock, but its role is brain death is not well described. Direct peritoneal resuscitation (DPR) improves visceral organ blood flow and has been shown to reduce inflammation after hemorrhagic shock. Better understanding of this inflammatory process within the peripheral organs, the effects of DPR, and the role of the intestine could aid in better resuscitation of potential organ donors. Methods: Male Sprague-Dawley rats were …

Immune Monitoring In Recipients Of Combined Living Donor Kidney And Hematopoietic Stem/Facilitating Cell Transplants., Mark Dewayne Badder

Electronic Theses and Dissertations

Solid organ transplantation coupled with a hematopoietic stem cell transplant from the organ donor allows for the recipient to cease immunosuppressive therapy after transplant via a chimeric immune system. This beneficial effect of stem cell transplants is negatively affected by graft versus host disease (GVHD). Better understanding of the donor and recipient’s immune system is vital to mitigating graft versus host disease and induction of donor chimerism without GVHD. In this study, flow cytometry was used to characterize immune cells of the recipients’ before and up to eighteen months post transplantation. The recipients were categorized into their respective chimeric groups. …

Establishing A Clinically Relevant Mouse Model Of Human Aml To Test Novel Transmethylation Inhibitors., Aditya Barve

Electronic Theses and Dissertations

Acute myeloid leukemia (AML) is a highly heterogeneous clonal disorder characterized by an accumulation of malignant immature myeloid progenitors in the bone marrow (BM) that hinder normal hematopoiesis. Patient AML exhibits a dramatic heterogeneity in terms of cytogenetics, disease morphology, and associated prognoses and/or chemotherapeutic sensitivity. Thus it becomes clearly evident that the investigation of novel therapeutics for AML will require model systems that are capable of recapitulating this stark heterogeneity in a patient specific manner. Furthermore, it is now understood that the surrounding bone marrow (BM) microenvironment and supporting cells play a critical role in leukemic progression as well …

The Impact Of The Patient Protection And Affordable Care Act’S Risk Adjustment Program On Adverse Selection : First Year Case Study., Steven K. Zimmerman

Electronic Theses and Dissertations

In 2014 the Patient Protection and Affordable Care Act (ACA) implemented a risk adjustment program to stabilize premiums and neutralize premiums in the individual health insurance marketplace. This dissertation will examine the impact of the ACA risk adjustment program on adverse selection for one insurer during 2014. This study utilized enrollment and claims data for one insurer and employs graphical analysis to test for adverse selection. Previous studies have been unable to utilize actual insurer data to test for adverse selection in under the ACA risk adjustment program. Until the implementation of the ACA, insurers relied on underwriting methods to …

Carnosine, A Therapeutic Potential For Critical Limb Ischemic., Adjoa Agyemang Boakye

Electronic Theses and Dissertations

Critical Limb ischemia (CLI) is a serious manifestation of peripheral artery disease. Advanced CLI patients are poor candidates for vascular surgeries. Numerous studies have shown that hypoxia inducible factor 1α (HIF1-α) plays an important role in recovery from murine hindlimb ischemia (HLI). HIF1-α is regulated by oxygen dependent prolyl hydroxylases (PHDs). Previous studies have shown that inhibition of PHDs by metal quenchers and viral delivery of HIF1-α improves blood flow to the ischemic limb. However, clinical trials with these therapies are largely negative partly because they do not address the underlying chronic oxidative stress. Based on recent observations that endogenous …

Vinyl Chloride-Diet Interactions In Liver Disease : Potential Roles Of Autophagy And Energy Management., Anna L. Lang

Electronic Theses and Dissertations

Vinyl chloride (VC) is a prevalent environmental toxicant that has been shown to cause liver injury at high, occupational exposures. However, most studies have not addressed interactions of low doses with risk-modifying factors. This study aims to explore low-level VC metabolite exposure interactions with other potential risk-modifying factors and their effect on underlying liver disease. We examined sub-hepatotoxic effects of a VC metabolite (chloroethanol, CE) in two murine models of liver injury using ethanol and lipopolysaccharide (LPS). In both, CE significantly enhanced liver injury when compared to either ethanol or LPS alone. Previous studies have shown an increase in mTOR …

Type 2 Diabetes Mellitus (T2dm) Onset And "Remission"., Srikanth Tangelloju

Electronic Theses and Dissertations

Background: Type 2 diabetes mellitus (T2DM) is a progressive disease condition. As the disease progresses the function of beta (β) cells (cells which regulate insulin) decline, thereby increasing the circulating blood glucose levels. If left unmanaged the disease progresses from onset to development of T2DM related complications and eventually death. When managed, in certain individuals, T2DM onset can be prevented and/or slowed down and in certain T2DM individuals, remission is observed. There are some known modifiable risk factors such as diet and physical activities that are associated with the speed and direction of progression, but much is still unknown. In …

Factors Associated With Self-Care Behavior In Persons With Heart Failure., Mohammed Munther Al-Hammouri

Electronic Theses and Dissertations

Introduction: Heart failure is a serious illness that mostly affects the elderly. It is characterized by progressive deterioration of the heart muscle and affects the quality of life of those living with it. The progression of the illness has been shown to be slower with appropriate self-care. Several studies examined predictors of self-care extensively. The results were inconsistent and usually explained a small fraction of the variance in self-care in persons with heart failure, and they usually overlooked some potential predictors that could be related to self-care in person with heart failure. Purpose: The purpose of this study was to …

Impact Of Luminance And Spatial Parameters On The Generation Of The Human Pattern Electroretinogram., Kate A. Godwin

Electronic Theses and Dissertations

The current work assessed some of the key hypotheses behind the generation of the pattern electroretinogram (PERG) response. The first of these hypotheses states that the PERG response is the result of linear cancellation of simultaneous increment and decrement retinal responses, as generated by the retinal ON- and OFF-pathways. Experiment 1 evaluated the possibility of simulating the PERG by summing the ERG responses elicited by increment and decrement flashes, and found that it was indeed possible to simulate the PERG from these responses. However, only the steady-state PERG could be modeled consistently. The second hypothesis evaluated a theory that the …

Multipurpose Tenofovir Disoproxil Fumarate Electrospun Fibers For The Prevention Of Hiv-1 And Hsv-2 Infections., Kevin Tyo

Electronic Theses and Dissertations

Sexually transmitted infections affect hundreds of millions of worldwide. Both human immunodeficiency virus (HIV-1 and -2) and herpes simplex virus-2 (HSV-2) remain incurable, urging the development of new prevention strategies. While current prophylactic technologies are dependent on strict user adherence to achieve efficacy, there is a dearth of delivery vehicles that provide discreet and convenient administration, combined with prolonged-delivery of active agents. To address these needs, we created electrospun fibers (EFs) comprised of FDA-approved polymers, poly(lactic-co-glycolic acid) (PLGA) and poly(DL-lactide-co-ε-caprolactone) (PLCL), to provide sustained-release and in vitro protection against HIV-1 and HSV-2. PLGA and PLCL EFs, incorporating the antiretroviral, tenofovir …

Peptoanaerobacter Stomatis Interactions With Neutrophils., Emeri Jimenez Flores

Electronic Theses and Dissertations

Peptoanaerobacter stomatis is a newly appreciated taxon, present in high numbers in oral biofilms from periodontal patients. However, little is known about this organism’s potential virulence and its interaction with the host immune response. Therefore, to better understand the role of P. stomatis in periodontitis, we studied its interactions with neutrophils. Human neutrophils were challenged with P. stomatis strain CM2 or S. aureus AF488 (positive control) for 30 min. Bacterial internalization was examined by ImageStreamX imaging flow cytometry. Bacterial viability was assessed by colony-forming unit assays and Baclight assays. Phagocytosis-stimulated respiratory burst response was measured by flow cytometry. The fusion …

The Role Of O-Glcnacase During Heart Failure., Sujith Dassanayaka

Electronic Theses and Dissertations

Global augmentation of protein O-GlcNAcylation occurs in response to a myriad of stressors and confers a survival advantage at the cellular level. This protective phenomenon has been demonstrated to mediate cardioprotection through various in vitro and in vivo studies during ischemia-reperfusion, myocardial infarction, and oxidative stress; however, relatively little is known of the regulation of protein O-GlcNAcylation. Protein O-GlcNAcylation is regulated by two antagonistic enzymes, namely, O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA). Ablation of cardiomyocyte OGT, the enzyme that catalyzes the addition of O-GlcNAc to proteins, exacerbates cardiac dysfunction during infarct-induced heart failure (HF). However, little is known of the …

Memory And Fine Motor Skill Test Performance Among Children Living Near Coal Ash Storage Sites., Lindsay Koloff Tompkins

Electronic Theses and Dissertations

Coal ash, a byproduct of coal combustion,is reduced in 47 U.S. states andfrequently contains heavy metals, some of which are known neurotoxins. An estimated 1.5 million children live near sites where coal ash is produced andstored, yet there have been no studies assessing coal ash exposure and children’s neuro behavioral health. This study is part of a larger cross-sectional study, Coal Ash and Neuro behavioral Symptoms in Children Aged 6- 14 Years Old, and aimed to determine the relationship between children’s memory and fine motor skill test performance and the proximity of the home to coal ash storage sites, the …

Air Pollution, Pulmonary Oxidative Stress, And The Endothelin System In The Development Of Cardiovascular Injury., Jordan B. Finch

Electronic Theses and Dissertations

The goal of this project was to examine the role of endothelin-1 (ET-1) as a mediator in the pathway between air pollution exposure and the development of vascular injury. A human cohort and male mice (C57BL/6 and ecSOD-Tg) were used to evaluate changes in the ET-1 system in response to exposures of fine particulate matter (PM2.5). Human ET-1 levels were significantly associated with environmental factors and markers of vascular change, but were decreased with increased PM2.5. No association was seen between ET-1 and endothelial progenitor cells (EPCs) except for EPC-4, possibly indicating a regulatory relationship with this specific population. In …

Developing A More Clinically-Relevant Mouse Model Of Cisplatin-Induced Nephrotoxicity., Cierra N. Sharp

Electronic Theses and Dissertations

Cisplatin is a nephrotoxic chemotherapeutic that causes acute kidney injury (AKI) in 30% of patients. Although recovery can occur after one episode of cisplatin-induced AKI, studies have indicated multiple episodes may lead to the development of chronic kidney disease (CKD), an irreversible disease with no current treatments. The standard mouse model of cisplatin-induced AKI consists of one, high dose of cisplatin (> 20 mg/kg) that is lethal to the animal three days later. This model doesn’t accurately reflect the repeated dosing regimen patients receive, and doesn’t allow for long-term outcome studies of pathologies associated with CKD. We have developed a …

Toll-Like Receptor 4 Mutation Suppresses Hyperhomocysteinemia-Mediated Hypertension., Anastasia Familtseva

Electronic Theses and Dissertations

Background: Hyperhomocysteinemia (HHcy) has been observed to promote hypertension, but the mechanisms are unclear. Toll-like receptor 4 (TLR-4) is a cellular membrane protein that is ubiquitously expressed in all cell types of the vasculature. TLR-4 activation has been shown to promote inflammation that has been associated with pathogenesis of hypertension. In this study, we hypothesize that HHcy induces hypertension by TLR-4 activation that promotes inflammatory cytokine up-regulation (IL-1β, IL-6, TNF-α) and initiation of mitochondrial dysfunction leading to cell death and chronic vascular inflammation. Methods: To test this hypothesis, we used C57BL/6J mice (WT); Cystathionine-β-synthase deficient mice (CBS+/-) with genetic mild …

Life Balance In Adult Healthy Siblings Of Individuals With Childhood Cancer., Yolanda Williams

Electronic Theses and Dissertations

Siblings of children who were diagnosed with cancer in childhood experience significant stress and psychological difficulties as a result of the cancer. Furthermore, the needs of siblings have often been overlooked in the cancer literature, prompting the need for more studies. The purpose of this dissertation is to examine the life balance and social support outcomes of adults who grew up in the household with a sibling that was diagnosed with cancer. The study sample consisted of 120 adult healthy siblings who grew up in a household with a sibling that was diagnosed with cancer prior to age 19. Participants …

The Discovery Of A Novel, Ras-Mediated Nore1a/Pmliv Tumor Suppressor Complex., Jessica Mezzanotte Sharpe

Electronic Theses and Dissertations

Ras is the most commonly activated oncogene in human cancer. Activated Ras drives cell growth and proliferation by activating multiple mitogenic signaling pathways. However, Ras also has the paradoxical ability to promote anti-growth, pro-apoptotic, and pro-senescent signaling. The signaling pathways of many of these biological effectors remain poorly defined. One group of proteins capable of promoting Ras-induced apoptosis and cell cycle arrest is the RASSF family of tumor suppressors. Novel Ras Effector 1A, or NORE1A, was the first member of this family discovered and is a bona fide tumor suppressor that is lost or inactivated in a number of different …

In Vivo Monitoring Of Therapeutic Efficacy And Virulence Profile By Bioluminescent Klebsiella Pneumoniae., Ramy Ameen Fodah

Electronic Theses and Dissertations

Klebsiella pneumoniae causes an acute respiratory infection in human with severe outcomes and high mortality rates even with antibiotic treatment. Even with its critical clinical importance, few virulence systems have been identified for K. pneumoniae limiting the development of new therapeutic strategies. Accordingly, we performed Next Generation sequencing for the strain ATCC 43816, a virulent strain in mouse respiratory disease models, and compared its genomic data with two previously sequenced strains NTUH-K2044 and MGH 78578 for the purpose of identifying genes required for colonizing host lungs. Furthermore, the virulence potential of the three K. pneumoniae strains were tested in a …

Characterization Of Pg1604 (Porz) As An Essential Component Of Type 9 Secretion System In Porphyromonas Gingivalis., Apurva Tadimari Prabhakar

Electronic Theses and Dissertations

Background: The numerous virulence factors of Porphyromonas gingivalis are essential for the organism to invade host tissues while escaping immune responses [1, 2]. Some of these factors, like major proteases referred to as gingipains, are secreted by a unique secretion system called PerioGate or Type IX Secretion System (T9SS). T9SS consists of a number of membrane and periplasmic proteins, which provide transportation only for proteins that possess a conserved C-terminal domain (CTD). The CTD functions as a specific recognition signal for the T9SS. PG1604 of P. gingivalis W83 is a CTD-containing protein, which has been shown in our initial studies …

Molecular Characterization Of Human Papillomavirus In Head And Neck Tumors., Sujita Khanal

Electronic Theses and Dissertations

Head and neck cancers (HNCs) are common causes of cancer-related deaths worldwide. An increasing incidence of subsets of HNCs is due to human papillomavirus (HPV). Other subsets are associated with tobacco and alcohol use. Determination of differential biomarkers and molecular mechanisms distinguishing HPV-associated and unassociated HNCs should improve diagnostic and therapeutic strategies. This study was designed to identify potential biomarkers for HPV detection, and to evaluate viral and host genetic and epigenetic mechanisms involved in HPV-associated HNCs. Overexpression of a cellular protein, p16INK4a, which is widely used as a surrogate marker for HPV-positive HNC, is non-specific because some HPV-negative cancers …