Medicine and Health Sciences Commons^™

Pharmacological Inhibition Of Cyclophilin Ameliorates Experimental Allergic Encephalomyelitis, Zi L. Huang

Theses and Dissertations

A subset of cyclophilins have been implicated in mechanisms of neuroinflammation and neurodegeneration that contributes to the pathogenesis of Multiple Sclerosis. Mitochondrial dysfunction leading to mitochondrial permeability transition plays a pivotal role in axonal damage and disease progression in Multiple Sclerosis. Cyclophilin D (CypD) is a crucial regulatory component of the mitochondrial permeability transition pore and it was demonstrated that the cyclophilin D knockout animals showed reduced experimental allergic encephalomyelitis (EAE) clinical disease severity and axonal injury. We investigated the effect of N-methyl-4-isoleucine-cyclosporin (NIM811), a non-immunosuppressive and non-selective cyclophilin inhibitor, on the course and severity of EAE. EAE mice treated …

Feasibility Of Integrating Tripterygium Wilfordii Into Modern Cancer Therapy For Increased Efficacy With Minimal Toxicity, Andy Vo

AUCTUS: The Journal of Undergraduate Research and Creative Scholarship

Cancer is the second leading cause of death in the U.S., and millions of novel cancer cases are being diagnosed each year. While chemotherapy and ionizing radiation are effective treatments against these malignant tumors, the adverse effects that accompany such treatments are devastating. In order to find alternative treatment methods with less side effects, we turn to Eastern herbal medicine. Recent scientific research has found that Tripterygium wilfordii, an herbal medicine traditionally used to treat inflammation in China, contains compounds (triptolide and celastrol) that prevent the growth of solid tumors, induce apoptosis, and prevent metastasis of developed tumors. Investigations on …

Comparison Of Treatment Planning Decisions When Combining Cbct And Digital Radiography Verses Digital Radiography Alone, Mckay Barlow Packer

Theses and Dissertations

Cone beam computed tomography (CBCT) is the recommended imaging modality of choice for evaluating previous endodontic treatment (1). The aim of this study was to compare treatment planning decisions made when evaluating previous endodontic treatment to determine if treatment planned and projected prognosis differs when digital radiography is used alone or in combination with CBCT. A retrospective chart review was conducted. Patients for whom a CBCT was taken were included in the study. Twenty-eight patients qualified. Patient’s periapical digital radiographs (Dexis©) were evaluated by 2 calibrated endodontists, a treatment plan was identified and a prognosis was projected. Later the same …

Characterization And Economic Burden Associated With Pediatric Opioid Exposures And Poisonings, Anisha M. Patel

Theses and Dissertations

Introduction

The main objectives of this study were: 1) to examine the prevalence and characteristics of opioid exposures, 2) to estimate the economic costs associated with opioid poisonings, and 3) to examine the characteristics associated with opioid poisoning-related health care resource use (HCRU) and costs in children.

Methods

Data from the National Poison Data System from January 1, 2010 to December 31, 2014 were utilized to examine the prevalence and characteristics of opioid exposures and poisonings in children <18 years. Economic costs were estimated using the 2012 Nationwide Emergency Department Sample, Kids’ Inpatient Database, Multiple Cause-of-Death file and other published sources, applying a societal perspective. Direct costs included costs associated with ED visits, hospitalizations and ambulance transports. Indirect cost included productivity costs due to caregivers’ absenteeism and premature mortality among children.

Results

There were a total of 83,418 pediatric opioid exposures and nearly half of them resulted in poisoning. The epidemiology of opioid …

Prevalence, Incremental Cost And Resource Utilization Associated With Opioid Overdoses, Batul Electricwala

Theses and Dissertations

Background –

An increase in opioid prescribing has led to an increase in opioid overdoses.^1,2 No study has estimated the incremental costs subsequent to an opioid overdose event in prescription opioid users, or the prevalence and costs of overdose events in family members of prescription opioid users and in overdose victims with no identifiable source of prescription opioid. The latter group will be referred to as “others”.

Objectives –

The first objective of this study was to estimate the prevalence of opioid overdoses in aforementioned groups. The second objective was to estimate the incremental costs and resource utilization associated …

Emerging Pathogens In Cystic Fibrosis Patients At Virginia Commonwealth University Medical Center (Vcumc), Emily M. Hill

Theses and Dissertations

Cystic fibrosis (CF) is an autosomal recessive disorder affecting 70,000 individuals worldwide. This disease is characterized by the buildup of mucus in the airways leading to chronic lung infections resulting in pulmonary failure and death in 95% of CF patients. Routine surveillance of CF pathogens using traditional microbiology culture guides management and treatment of CF patients. Molecular profiling studies have revealed emerging pathogens that may play a role in CF lung disease by either directly causing infection or upregulating the virulence factors of classic CF pathogens, such as P. aeruginosa; however, routine CF culture protocols have not been modified …

Chronic Pain Causal Attributions In An Interdisciplinary Primary Care Clinic: Patient-Provider And Provider-Provider Discrepancies, Bryan Jensen

Theses and Dissertations

The purpose of the present study was to investigate the influence of pain causal attributions on patient pain-related functioning, treatment engagement, and clinical outcomes. Additionally, the impact of discordant pain causal attributions between patients and their providers as well as between interdisciplinary providers was examined. Patients rated their pain functioning and causal pain attributions during a regular clinic visit. Following the patient’s visit both the behavioral medicine provider and internal medicine resident provided ratings of similar pain-related functioning domains and causal attributions. Follow-up data were collected from the electronic medical record three months following that clinic visit. Overall, results revealed …

Autotaxin In Central Nervous System Development And Disease, Natalie A. Wheeler

Theses and Dissertations

During development, oligodendrocytes (OLGs), the myelinating cells of the central nervous system (CNS), undergo a stepwise progression during which OLG progenitors, specified from neural stem/progenitor cells, differentiate into fully mature myelinating OLGs. This progression along the OLG lineage is characterized by well-synchronized changes in morphology and gene expression patterns. The studies presented in this dissertation identified the extracellular factor Autotaxin (ATX) as a novel upstream signal modulating HDAC1/2 activity and gene expression in cells of the OLG lineage. Using the zebrafish as an in vivo model system, as well as rodent primary OLG cultures, this functional property of ATX was …

Nest - Caring For The Caregiver, Ashley Whitehead

Theses and Dissertations

Today, more than ever, there exists an overlap between hospitality and healthcare industries; with the impact being felt in the way hospital interiors are designed. This influence impacts the patient’s experience but focuses very little on the experience of the caregiver. Caring for a sick child takes an emotional, mental, and physical toll on a family. It is especially challenging to care for a sick family member when away from the comfort and security of the family’s private home. This project explores that challenge through the interior design of a space that, for both patient and family, is restorative, healing, …

Influence Of Public Insurance On Healthcare Access And Cancer Care, Wafa W. Tarazi

Theses and Dissertations

Medicaid expansion under the Affordable Care Act (ACA) facilitates access to care among vulnerable populations, but 21 states have not yet expanded the program. Tennessee’s Medicaid program experienced a dramatic Medicaid contraction when the program disenrolled approximately 170,000 nonelderly adults in 2005. Pre-ACA expansions were associated with better access to and utilization of healthcare services. However, little is known about the effect of these policy changes on improvement in health outcomes for women diagnosed with breast cancer, access to care for cancer survivors, and the effect of generosity and duration of expansion on access to care.

This dissertation has three …

Development And Evaluation Of A Peer-To-Peer Intervention To Increase Self-Management Among Adult In-Center Hemodialysis Patients, Jennifer J. St Clair Russell

Theses and Dissertations

Background: Peer-to-peer (P2P) support programs have the potential to assist ESRD patients in managing their disease and improve outcomes. Yet, there is little research examining P2P programs’ impact on psychosocial outcomes and disease management behaviors.

Methods: A 4-month P2P mentoring intervention was designed and piloted in a facility serving 249 in-center hemodialysis patients in Lynchburg, Virginia. Preceded by a social marketing effort, which included a program naming contest and participant recruitment, the intervention included: (1) mentor training, (2) pairing of mentees and mentors, (3) kick-off social mixers, (4) ongoing meetings between mentees and mentors, (5) mentor training booster, and (6) …

Cancer Health Literacy And Hospitalization In The First Five Years Following A Cancer Diagnosis, Laura A. Cartwright

Theses and Dissertations

BACKGROUND: The field of health literacy research has been focused recently on developing more accurate measurement tools and understanding the relationship between health literacy and health outcomes. Individuals with lower levels of health literacy have worse health outcomes, including hospitalization rates, compared to those with adequate health literacy. This relationship has yet to be examined in the cancer patient population, although significant relationships between health literacy and cancer knowledge, screening behavior and quality of life have been found. This study is the first to examine the relationship between health literacy and hospitalization rates in a cancer patient population, and the …

The Incidence Of Root Dentinal Micro-Cracks Caused By Reciprocating And Continuous Rotary Instrumentation, Stephen N. Schroeder

Theses and Dissertations

The aim of this study was to compare the incidence of root canal dentinal micro-cracks after canal instrumentation using reciprocating files (WaveOne Gold® and Twisted Adaptive®) and continuous rotation files (Edge Evolve® and EndoSequence®) in an ex-vivo benchtop study. This project used a novel methodology of finding dentinal defects using the “K-cube”, which allows evaluators to visualize sectioned root surfaces before instrumentation and after instrumentation. Mesial roots from 40 human mandibular first molars were divided into 4 groups of 10 for each file type. Root section pictures were taken with a Zeiss Discovery V20 stereomicroscope before and after canal instrumentation. …

Motives For Participation In Triathlons Among Midlife To Older Black Women: A Mixed Method Study, Candace Brown

Theses and Dissertations

BACKGROUND: Research has established the positive link between physical activity and its impact on health among adults. Generally, as people get older, they are less likely to be active. Black women comprise 13% of the women in the US but constitute 52% of women who are inactive. Existing articles on exercise motivation among Black women have generally assessed sedentary individuals. Little research has examined the motivations to exercise among physically active Black women. METHODS: Guided by the regulators of the Self Determination Theory, the 56 item Motivations of Marathoners Scales for Triathletes (MOMS-T) was used to assess the motives of …

Obesity And Asthma: Adiponectin Receptor 1 (Adipo R1) And Adiponectin Receptor 2 (Adipo R2) Are Expressed By Normal Human Bronchial Epithelial (Nhbe) Cells At Air-Liquid Interface (Ali) And Expression Changes With Il-13 Stimulation, Jennifer L. Bradley

Theses and Dissertations

Obesity is recognized as an important risk factor for the development of many chronic diseases such as hypertension, Type 2 diabetes mellitus (T2DM) cardiovascular disease, cancer, renal disease, neurologic dysfunction, metabolic syndrome and asthma (3, 4). Circulating serum adiponectin levels in obese asthmatics have been reported to be low. Therefore, we aimed to investigate the role of adiponectin in a mucus hypersecretion model and hypothesized that adiponectin would decrease IL-13 induced MUC5AC expression from differentiated NHBE cells and that increasing concentrations of IL-13 would cause a decrease in Adipo R1 and Adipo R2 expression. MUC5AC expression with exposure to adiponectin …

A Study Of The Action Of Risperidone At 5-Ht2a Receptors, Supriya A. Gaitonde

Theses and Dissertations

Risperidone is an ‘atypical’ antipsychotic and is approved by the USFDA mainly for the treatment of schizophrenia and symptoms of bipolar disorder. Risperidone (an SDA or serotonin-dopamine antagonist) has ~20-fold higher affinity at 5-HT_2A receptors over dopamine D₂ receptors, which makes it more efficacious against the negative symptoms of schizophrenia and less liable to causing extrapyramidal side effects than ‘typical’ antipsychotics.

The major goal of the current investigation was to study the structure of risperidone and to identify the minimum structural features required for 5-HT_2A receptor affinity that retain antagonist action. The structure of risperidone was systematically …

The Effect Of Pre-Deployment Physiology As A Predictor Of Post-Traumatic Stress Disorder Among A Sample Of United States Army National Guard And Reserve Soldiers, David J. Rothman

Theses and Dissertations

Potential risk factors for development of Post-Traumatic Stress Disorder (PTSD) are still unclear. One potential risk factor for the development of PTSD is an individual’s cardiovascular reactivity and recovery in response to stressor tasks. The current study was conducted with 763 Army National Guard and Army Reserve soldiers. Participants completed a stressful induction along with self-report measures prior to deployment. Post-deployment, self-report measures were completed to assess PTSD symptomatology and experiences related to deployment and combat. Multiple regression was used to determine the ability of blood pressure response to stress to predict PTSD symptoms immediately and one-year after return from …

N-Methyl 4-Methyl Amphetamine N-Alkyl Chain Extension Differentially Affects Ion Flux At The Human Dopamine And Norepinephrine Transporters, Alan C. Harris Jr.

Theses and Dissertations

Amphetamine (AMPH) and its derivatives embody a remarkable breadth of pharmacology. These molecules exert their effects, both therapeutic and pathological, at the human monoamine transporters, which tune synaptic dynamics by evacuating monoamine neuromodulators from the synapse subsequent to neuronal impulses. These transporters are electrogenic, and the transporter-mediated current can be correlated to a surrogate measure of the change in membrane voltage: Ca⁺⁺ currents from co-transfected L-type Ca⁺⁺ channels. The present work makes use of this assay, with which it is possible to derive pharmacodynamic metrics from both substrates and inhibitors. This work presents data on a heretofore-unstudied class …

Pharmacological Implications Of Adenosine 2a Receptor- Dopamine Type 2 Receptor Heteromerization, Candice N. Hatcher-Solis

Theses and Dissertations

G protein-coupled receptors (GPCRs) are heptahelical, transmembrane proteins that mediate a plethora of physiological functions by binding ligands and releasing G proteins that interact with downstream effectors. GPCRs signal as monomers, complexes of the same receptor subtype (homomers), or complexes of different receptor subtypes (heteromers). Recently, heteromeric GPCR complexes have become attractive targets for drug development since they exhibit distinct signaling and cell-specific localization from their homomeric counterparts. Yet, the effect of heteromerization on the pharmacology of many GPCR homomers remains unknown. Therefore, we have undertaken the task to examine the effect of heteromerization on G_s signaling through the …

Predictors Of Caffeine-Related Withdrawal Symptoms In College Freshmen, David J. Pomm

Theses and Dissertations

While caffeine withdrawal has been well-characterized, research on caffeine intake and factors associated with withdrawal has been limited. The present study examined prevalence rates of caffeine use and identified psychosocial factors associated with having caffeine withdrawal headaches (CWH). Participants were N = 1,989 college freshmen who participated in the 2011 Spit for Science project. Caffeine use was reported by 80% of the sample. Females were more likely than males to consume caffeine, and soda was the primary source of caffeine for both genders. As hypothesized, daily caffeine users were more likely to report CWH than non-daily users. When multivariable analyses …

Continuous Stationary Phase Gradients For Planar And Column Chromatography, Veeren Dewoolkar

Theses and Dissertations

Surfaces that exhibit a gradual change in their chemical and/or physical properties are termed as surface gradients. Based on the changes in properties they are classified either as physical or chemical gradients. Chemical gradients show variations in properties like polarity, charge, functionality concentration and have found potential applications in fields of biology, physics, biosensing, catalysis and separation science. In this dissertation, surface gradients have been prepared using controlled rate infusion (CRI).

CRI is a simple method in which a surface gradient is formed by carrying out the infusion of organoalkoxysilane in a time-dependent fashion using a set infusion rate. Depending …

Radioprotective Cerium Oxide Nanoparticles: Molecular Imaging Investigations Of Conps’ Pharmacokinetics, Efficacy, And Mechanisms Of Action, Philip R. Mcdonagh Iii

Theses and Dissertations

Cerium oxide nanoparticles (CONPs) are being investigated for several anti-oxidant applications in medicine. One of their most promising applications is as a radioprotective drug, an area of research in need due to the severe side effects from radiation therapy. In this work, the potential of CONPs as a radioprotective drug is examined using four criteria: favorable biodistribution/pharmacokinetics, low toxicity, ability to protect normal tissue from radiation damage, and lack of protection of tumor. The mechanisms of action of CONPs are also studied. Biodistribution was determined in radiolabeled CONPs with surface coatings including citrate, dextran T10-amine (DT10-NH₂), dextran T10-polyethylene …

“I Just Need To Get Myself Supervised:” Exploring Transformative Learning In The Development Of Professionalism Among Physicians In The First Year Of Graduate Medical Education, Elizabeth P. Marlowe

Theses and Dissertations

The study explored the learning experiences of first-year resident physicians during the first year of graduate medical education. The experiences of four intern physicians in the first year of residency training at an urban academic health system provided the site for the research. An exploratory case study research design was employed to examine the learning experiences of these new physicians. A qualitative approach was used to analyze data from interviews and ethnographic observations. The findings of this research study provide evidence surrounding how and what these physician trainees learned regarding professionalism during the first year of residency training.

The findings …

Irreversible Zinc Block Of The Swelling-Activated Chloride Current In Di Tnc1 Astrocytes, Noah Belkhayat

Theses and Dissertations

The swelling-activated chloride current, commonly referred to as ICl,swell, is an outwardly-rectifying anion current that plays an important role in cell volume regulation, among other capacities. Despite several decades of research, the molecular identity of the channel responsible for this chloride current remains controversial. Recent indications that key endogenous sulfhydryl groups are capable of modifying the current led us to assess the effects of several divalent cations, including zinc, on ICl,swell. Zinc is known to tightly associate with sulfhydryl groups such as in zinc finger proteins. We found that extracellular zinc irreversibly inhibited ICl,swell at a site downstream in the …

Probing Allosteric, Partial Inhibition Of Thrombin Using Novel Anticoagulants, Stephen S. Verespy Iii

Theses and Dissertations

Thrombin is the key protease that regulates hemostasis; the delicate balance between procoagulation and anticoagulation of blood. In clotting disorders, like deep vein thrombosis or pulmonary embolism, procoagulation is up-regulated, but propagation of clotting can be inhibited with drugs targeting the proteases involved, like thrombin. Such drugs however, have serious side effects (e.g., excessive bleeding) and some require monitoring during the course of treatment. The reason for these side effects is the mechanism by which the drugs’ act. The two major mechanisms are direct orthosteric and indirect allosteric inhibition, which will completely abolish the protease’s activity. Herein we sought an …

Provision Of Hospital-Based Palliative Care And The Impact On Organizational And Patient Outcomes, Marisa L. Roczen

Theses and Dissertations

Hospital-based palliative care services aim to streamline medical care for patients with chronic and potentially life-limiting illnesses by focusing on individual patient needs, efficient use of hospital resources, and providing guidance for patients, patients’ families and clinical providers toward making optimal decisions concerning a patient’s care. This study examined the nature of palliative care provision in U.S. hospitals and its impact on selected organizational and patient outcomes, including hospital costs, length of stay, in-hospital mortality, and transfer to hospice. Hospital costs and length of stay are viewed as important economic indicators. Specifically, lower hospital costs may increase a hospital’s profit …

Markerless Lung Tumor Trajectory Estimation From Rotating Cone Beam Computed Tomography Projections, Shufei Chen

Theses and Dissertations

Respiration introduces large tumor motion in the thoracic region which influences treatment outcome for lung cancer patients. Tumor motion management techniques require characterization of temporal tumor motions because tumor motion varies patient to patient, day to day and cycle to cycle. This work develops a markerless algorithm to estimate 3 dimensional (3D) lung-tumor trajectories on free breathing cone beam computed tomography (CBCT) projections, which are 2 dimensional (2D) sequential images rotating about an axis and are used to reconstruct 3D CBCT images.

A gold standard tumor trajectory is required to guide the algorithm development and estimate the tumor detection accuracy …

Involvement Of Signal Peptidase I In Streptococcus Sanguinis Biofilm Formation, Jessica Aynapudi

Theses and Dissertations

Biofilm accounts for 65%-80% of microbial infections in humans. Considerable evidence links biofilm formation to oral disease and consequently systemic infections. Eradication of biofilm-associated infections is important. Streptococcus sanguinis, a Gram-positive bacterium, is one of the most abundant species in oral biofilm. It contributes to biofilm development in oral cavities and is one of the recognized causes of infective endocarditis. To study and identify biofilm genes in S. sanguinis, biofilm formation of 51 mutants was compared with the wild type SK36 strain using crystal violet (CV) staining in a microtiter plate. Confocal laser scanning microscopy (CLSM) and image analysis was …

Introducing Novel Combinatorial Targeted Therapies In Multiple Types Of Cancer, Mehrad Tavallai

Theses and Dissertations

The cancers of liver, colon and breast are amongst the top five most prevalent and most fatal worldwide. As the Raf/MEK/ERK pathway is frequently deregulated in hepatocellular carcinoma (HCC), sorafenib, a Raf kinase inhibitor, became the first systemic therapy approved for the treatment of patients with HCC. However, sorafenib only produced modest effects with low response rates in the clinic. Similarly, regorafenib, which was approved for the treatment of metastatic colorectal cancer (CRC), has had a poor response rate in the clinic. Since phosphodiesterase type 5 has been reported to be overexpressed in HCC and CRC, we hypothesized that sildenafil, …

Drug And Vaccine Development For Neisseria Gonorrhoeaea, Devin R. Cash

Theses and Dissertations

Neisseria gonorrhoeae, the causative agent of the STI gonorrhea, is not preventable by vaccination and is rapidly developing resistance to antibiotics. One important strategy for gonococcal survival in the host is iron acquisition in the face of nutritional immunity. To overcome iron limitation, the gonococcus expresses TonB dependent transporters (TdTs), outer membrane proteins that facilitate nutrient acquisition. Of the TdTs, the transferrin (Tf), lactoferrin (Lf), and hemoglobin (Hb) receptors hijack iron directly from host proteins, and studies have already shown that the Tf receptor is essential for the initiation of human infection. Given that the TdTs are virulence factors, …