Mitochondrial Biogenesis And Electrical Properties Of Hpsc-Derived Motor Neurons, Laura O'Brien

Theses and Dissertations

Human pluripotent stem cells (hPSCs), including human embryonic stem cells (hESCs) and induced pluripotent stem cells (iPSCs) hold great promise in the fields of drug development and regenerative medicine. If iPSCs reprogrammed from patient cells replicate what is seen in vivo they may be used as a model of disease. A process that is disrupted in many neurodegenerative diseases is mitochondrial biogenesis. One of these diseases is amyotrophic lateral sclerosis (ALS), which is characterized by loss of motor neurons in the brain and spinal cord. Differentiation of hPSCs into motor neurons offers a way to study a previous unavailable cell …

Development Of Non-Traditional Platinum Anticancer Agents: Trans-Platinum Planar Amine Compounds And Polynuclear Platinum Compounds, Daniel E. Lee

Theses and Dissertations

Development of Non-Traditional Platinum Anticancer Agents: trans-Platinum Planar Amine Compounds and Polynuclear Platinum Compounds

By Daniel E. Lee, Ph.D.

A dissertation submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy at Virginia Commonwealth University.

Virginia Commonwealth University, 2015

Major Director: Nicholas P Farrell, Ph.D., Professor, Department of Chemistry

Platinum anticancer compounds with cis geometry, similar to cisplatin, have been explored to circumvent the cisplatin resistance; however, they were not considered broadly active in cisplatin cells due to exhibiting similar or same cell death mechanism as cisplatin. Platinum compounds with trans geometry were less studied …

A Justification For The Trend Towards Indirect Pulp Therapy, Marissa Kuhnen

Theses and Dissertations

Purpose: The purpose of this retrospective chart review was to determine how primary molars needing vital pulp therapy have been treated in the past four years at Virginia Commonwealth University (VCU) and to determine which treatments: indirect pulp therapy (IPT), formocresol pulpotomy, and ferric sulfate pulpotomy have been successful. Methods: AxiUm records that contained the procedure codes D3120 (Pulp Cap – Indirect) or D3220 (Therapeutic Pulpotomy) were totaled by year. Visit records were queried again to identify treatment failures i.e. extractions or pulpectomy. Results: In 2010, 52% of vital pulp therapies were ferric sulfate pulpotomies and in …

Identifying Problems During Transitions Of Care And Reasons For Emergency Department Utilization In Community-Dwelling Older Adults, Antoinette B. Coe

Theses and Dissertations

A mixed methods approach was used for this study. The setting was a low-income, subsidized housing apartment building for community-dwelling older and younger disabled adults identified as a health care hot spot due to high rates of ambulance use. The study purpose was to identify reasons for ED use and problems during transition from ED to home, predictors of zip code 23220 (health care hot spot) in emergent and non-emergent ED visits, and predictors of total ED costs in community-dwelling older adults living in a health care hot spot. Semi-structured interviews with residents who used the ED, an existing database …

Axon Initial Segment Stability In Multiple Sclerosis, Suneel K. Thummala

Theses and Dissertations

Multiple sclerosis (MS) is an autoimmune disease of the central nervous system characterized by inflammation and demyelination. In addition to these hallmark features, MS also presents with axonal pathology, which is likely responsible for the signs and symptoms of the disease. Although prominent in MS, axonal pathology is frequently considered a consequence of demyelination and not a primary event. This conclusion is consistent with demyelination inducing the loss of specific axonal domains, known as the nodes of Ranvier that are responsible for the propagation of action potentials along the axon. In contrast, we propose that axonal pathology associated with MS …

Workplace Discrimination And Visual Impairment: An Analysis Of Eeoc Charges And Resolutions, Jane Mcneil

Theses and Dissertations

Workplace discrimination for individuals with visual impairments in the U.S. is an ongoing issue dating before the founding of the EEOC and the enactment of the ADA. Despite laws enacted to protect against unequal treatment in the workplace, the EEOC continues to receive submissions of formal discrimination charges from individuals with visual impairments.

The workplace is experiencing changes with increasing amounts of older adults, women, minorities, and the use of technology and the Internet. By examining characteristics of the discrimination charges and the resulting outcomes, the knowledge gained can describe the current situation and the historical progression of workplace discrimination …

Relieving Post-Stroke Fatigue Using A Group-Based Educational Training Approach, Catherine E. Emery

Theses and Dissertations

Post-stroke fatigue is a common problem that may limit participation in everyday activities. Emerging evidence suggests that group-based training in fatigue management may be an efficient means of reducing the effects of post-stroke fatigue. This mixed methods, quasi-experimental study proposed to determine whether a group-based educational program could be successful in relieving post-stroke fatigue and improving participation in daily activities. A convenience sample of stroke survivors (n=20) from retirement communities in southeastern PA were invited to participate in the research. Participants were screened for depression, motor and cognitive recovery, and sleep quality. Fatigue was measured using the Fatigue Severity Scale …

Crown Size Comparisons In Patients With Unilateral Palatally Displaced Canines, Joseph Eliason, Steven J. Lindauer

Theses and Dissertations

Abstract

CROWN SIZE COMPARISONS IN PATIENTS WITH PALATALLY DISPLACED CANINES

By Joseph L. Eliason, D.D.S.

A thesis submitted in partial fulfillment of the requirements for the degree of Master of Science in Dentistry at Virginia Commonwealth University.

Virginia Commonwealth University, 2015

Thesis Director: Steven J. Lindauer, D.M.D., M.Dent.Sc.

Professor and Chair, Department of Orthodontics

There has been significant debate over the past decades regarding the etiology of palatally displaced canines. Theorized risk factors include agenesis or malformation of the lateral incisors, incisor retroclination, transverse deficiency, or genetic predisposition. The purpose of this study is to compare the linear and volumetric …

Understanding The Function Of Dyrk1a Through Characterization Of Its Interacting Proteins, Varsha Ananthapadmanabhan

Theses and Dissertations

DYRK1A is a protein kinase encoded by a gene implicated in Down syndrome pathogenesis. Loss of DYRK1A could promote oncogenic transformation. However, the regulation and substrates of DYRK1A are not fully understood. MudPIT proteomic analysis revealed novel DYRK1A interacting proteins with poorly characterized or even unknown functions. Therefore, the aim of this thesis was to understand the function of DYRK1A through the characterization of its interacting proteins. To achieve this aim, we established stable cell lines expressing these proteins and confirmed the interactions between DYRK1A and seven candidate binding partners. Furthermore, we found that all novel DYRK1A-interacting proteins also bind …

Development And Validation Of A Discrete Event Simulation Model To Evaluate The Long Term Use Of Electronic Cigarettes In Us Population, Kunal Saxena

Theses and Dissertations

Introduction: Cigarette smoking is associated with lung cancer, cardiovascular disease, and chronic respiratory conditions. It is responsible for high mortality and morbidity risk in the US population. Smokers find sudden quitting difficult and it is reported that a large number of unassisted quitting attempts are eventually unsuccessful. Electronic cigarette or e-cig is a novel battery-driven, nicotine delivery product, currently being used as a smoking cessation tool by current and former smokers. Since its resemblance to a conventional cigarette, and its non-combustible nature, e-cig use has risen exponentially in the last few years. To address such public health issues, the US …

Characterization Of A Novel Protease In Staphylococcus Aureus, Adam L. Johnson

Theses and Dissertations

A newly discovered cysteine protease, Prp, has been shown to perform an essential, site-specific cleavage of ribosomal protein L27 in Staphylococcus aureus. In Firmicutes and related bacteria, ribosomal protein L27 is encoded with a conserved N-terminal extension that must be removed to expose residues critical for ribosome function. Uncleavable and pre-cleaved variants were unable to complement an L27 deletion in S. aureus, indicating that this N-terminal processing event is essential and likely plays an important regulatory role. The gene encoding the responsible protease (prp) has been shown to be essential, and is found in all organisms …

High-Throughput Data Analysis: Application To Micronuclei Frequency And T-Cell Receptor Sequencing, Mateusz Makowski

Theses and Dissertations

The advent of high-throughput sequencing has brought about the creation of an unprecedented amount of research data. Analytical methodology has not been able to keep pace with the plethora of data being produced. Two assays, ImmunoSEQ and the cytokinesisblock micronucleus (CBMN), that both produce count data and have few methods available to analyze them are considered.

ImmunoSEQ is a sequencing assay that measures the beta T-cell receptor (TCR) repertoire. The ImmunoSEQ assay was used to describe the TCR repertoires of patients that have undergone hematopoietic stem cell transplantation (HSCT). Several different methods for spectratype analysis were extended to the TCR …

An Association Study Between Adult Blood Pressure And Time To First Cardiovascular Disease, Yongjia Pu

Theses and Dissertations

BACKGROUND: Several studies have demonstrated the association between the time to hypertension event and multiple baseline measurements for adults, yet other survival cardiovascular disease (CVD) outcomes such as high cholesterol and heart attack have been somewhat less considered. The Fels Longitudinal Study (FLS) provides us an opportunity to connect adult blood pressure (BP) at certain ages to the time to first CVD outcomes. The availability of long-term serial BP measurements from FLS also potentially allows us to evaluate if the trend of the measured BP biomarkers over time predicts survival outcomes in adulthood through statistical modeling.

METHODS: When the reference …

Cost Effectiveness Of Warfarin In Anticoagulant Clinic After Introduction Of Dabigatran For Stroke Prevention In Atrial Fibrillation Patients In The United States, Mai Alhazami

Theses and Dissertations

OBJECTIVES: To assess cost effectiveness of anticoagulant clinics after FDA approval of New Oral Anticoagulants (NOACs) for preventing ischemic stroke in Atrial Fibrillation (AF) patients in the United States. METHODS: A decision tree was built to compare cost and effectiveness of 150mg dabigatran twice a day to adjusted dose of warfarin within anticoagulation clinic. The analysis was for one year using a societal perspective. The population in this analysis was a cohort of AF patients, ≥ 65 years old, with a CHADS₂ score>2, and no contraindication to anticoagulation. RESULTS: The base case analysis showed that changing from warfarin …

Elaboration And Design Of Α7 Nachr Negative Allosteric Modulators, Osama I. Alwassil

Theses and Dissertations

α7 Neuronal nicotinic acetylcholine receptors are one of two major classes of receptors responsible for cholinergic neurotransmission in the central nervous system. The existence of α7 neuronal nAChRs in different regions of the nervous system suggests their involvement in certain essential physiological functions as well as in disorders such as Alzheimer’s disease (AD), drug dependence, and depression. This project was aimed toward the discovery and development of small–molecule arylguanidines that modulate α7 nAChR function with improved subtype-selectivity through an allosteric approach. Identifying the required structural features of these small molecules allowed optimization of their negative allosteric modulator (NAM) actions at …

A Comparison Of Vitamin D Levels In Children With Early Childhood Caries, Vanessa O. Hofilena

Theses and Dissertations

Purpose: To determine if there is an association between early childhood caries (ECC) and vitamin D deficiency, as measured via a serum sample. An exploratory goal was to investigate the possibility of measuring vitamin D with a salivary assay. Methods: Serum samples of patients who were scheduled for a dental or otolaryngology procedure under general anesthesia were assessed for 25-hydroxyvitamin D (25(OH)D), parathyroid hormone and calcium. Results: Our analysis indicates that the vitamin D levels of the controls and ECC group were significantly different. There were significant inverse correlations between: 1) PTH levels and vitamin D and 2) decayed, missing, …

Motivational Factors For Treating Patients With Special Health Care Needs, Arpi Patel

Theses and Dissertations

Purpose: The purpose of this study is to assess what training and motivational factors dental providers report in providing dental care to PSHCN (patients with special healthcare needs. Materials and Methods: An electronic questionnaire was sent to n=104 fourth year dental students, n=147 general dentists with a specific continuing education course pertaining to PSCHN, and n=140 pediatric dentists in Virginia. The questionnaire consisted of four sections including Demographics, Professional Attitudes, Special Needs Patients and Motivational Factors, and PSCHN Cases. Results: The overall response rate for our study was 21%. The response rates of dental students, general dentists, …

Economic Impact Of Waste In Prescribing, Dispensing, And Medication Consumption In The United States, Sarah Almanie

Theses and Dissertations

Abstract

ECONOMIC IMPACT OF WASTE IN PRESCRIBING, DISPENSING, AND MEDICATION CONSUMPTION IN THE UNITED STATES

By Sarah A. Almanie, M.S.

A thesis submitted in partial fulfillment of the requirements for the degree of Master of Science at Virginia Commonwealth University.

Virginia Commonwealth University, 2015.

Major Director: David A. Holdford, R.Ph., M.S., Ph.D., FAPhA

Professor

Department of Pharmacotherapy and Outcomes Science

OBJECTIVES: This research examines waste associated with the medication use process which consists of unfilled prescriptions, abandoned prescriptions, or unused prescription medications. The aim of this study is to quantify the direct medical costs of medication waste in delivery of …

Neural Correlates Of Verb Argument Structure Processing, Svetlana Malyutina

Theses and Dissertations

Verb argument structure (VAS) is pivotal to sentence production and comprehension, since it determines participant roles, as well as their grammatical form and syntactic position in a sentence. Neural correlates of VAS processing have mainly been studied in terms of the number of arguments. Data on the neural and behavioral effects of other VAS characteristics are limited, whereas they would have implications for behavioral and brain stimulation treatments of language disorders.

The present research investigated behavioral and neural effects of three understudied VAS characteristics (number of subcategorization options, number of thematic options and number of number-of-argument options) in single-word-level and …

The Relationship Of The Mediterranean Diet And The Dietary Approaches To Stop Hypertension (Dash) Style Diet With Cardiometabolic Health, Yong-Moon Park

Theses and Dissertations

Introduction: Much evidence shows that the Mediterranean diet and the Dietary Approaches to Stop Hypertension (DASH) style diet are associated with risk reduction of cardiometabolic disease as well as lower risk of all-cause, cardiovascular disease (CVD), and cancer mortality. A subgroup of obese individuals (metabolically healthy obese (MHO) phenotype) and normal weight individuals (metabolically obese normal weight (MONW) phenotype) have been identified to have different cardiometabolic risks compared with their counterparts in the same category of body mass index (BMI). Scarce evidence exists demonstrating a relationship between adherence to Mediterranean diet or DASH style diets with MHO and MONW …

Maternal Obesity, Gestational Weight Gain And Offspring’S Asthma, Kristen Polinski

Theses and Dissertations

Introduction: Obesity is common among women of childbearing age and intrauterine exposures may influence the development of early childhood asthma. A handful of studies have investigated pre-pregnancy obesity, but even fewer have thoroughly explored gestational weight gain as possible childhood asthma risk factors. Gaps remain in the literature and to our knowledge, none have longitudinally explored these relationships in a nationally representative sample of U.S. children.

Methods: We used data from the Early Childhood Longitudinal Study – Birth Cohort, in which children were followed through age four (n≈5,200). Asthma was based on parent report of a physician’s diagnosis. …

Patterns Of Sedentary Behavior And Association With Health Risks Among African American Adults, Tatiana Y. Warren-Jones

Theses and Dissertations

Introduction: There is growing and compelling evidence suggesting time spent in sedentary behaviors (SB) is a unique contributor to health risk that appears to be independent of time spent in moderate- and/or vigorous-intensity physical activity (PA). However, few studies have examined these associations in women and even fewer studies have included ethnic minority populations.

Purpose: The major objectives of this study were to: (1) describe patterns of objectively measured sedentary and PA behaviors and variation in these behaviors in African American (AA) adults; (2) assess the association between bouts of and breaks in SB and waist circumference risk, body mass …

Geographic Accessibility To Health Services And Neonatal Mortality Among Very Low Birthweight Infants In South Carolina, Portavia Featherstone

Theses and Dissertations

Introduction: Infant mortality is commonly denoted as a marker of population health with more than half of all infant deaths occurring during the neonatal period (0-27 days) of infancy. Mortality for infants born very low birthweight (<1500 grams) is markedly higher than the babies born with normal birthweight (2500-4000 grams). The purpose of this research project was to assess geographic access to perinatal health services and the risk of neonatal death among infants born with very low birth weight. Data and methods: The linked birth and death records of a retrospective cohort of very low birthweight (<1500 grams) infants born in South Carolina between the years 2010 and 2012 were used (n=3191). We assessed the impact of travel time from maternal residence to delivery hospital and travel time from maternal residence to the nearest prenatal care provider (obstetricians/gynecologists, community health center, or rural health clinic). Logistic regression modeling was performed with adjustments for maternal characteristics (race, age, chronic/gestational hypertension, chronic/gestational diabetes mellitus, smoking, prenatal care), newborn characteristics (gestational age, birthweight, gender, NICU admission at birth), and the birth in a level III hospital. Results: There were a total of 563 neonatal deaths in this population and the neonatal mortality rate was 17.64 neonatal deaths per 100 live births. We did not find significant associations of travel time from maternal residence to delivery hospital and to a closest prenatal care provider with neonatal death after adjusting for confounders. However, we found that a one-week increase in gestational age (OR: 0.61 [95% CI: 0.57-0.65]) and non-Hispanic Black mothers (versus non-Hispanic White mothers) (OR: 0.65 [95% CI: 0.45-0.94]), were associated with the lower odds of neonatal death, while non-NICU admission at birth (OR: 5.99 [95% CI: 4.05-8.84]) was associated with an increased odds of neonatal death. Conclusion: Although we did not find that travel time was associated with neonatal mortality among very low birthweight infants, our study identified a few significant correlates for neonatal deaths in this birthweight group. Future studies should investigate the role of geographic access to care on mortality during other periods of infancy and among other birthweight groups.

Effects Of Tgf-Β1 And Il-33 On Mast Cell Function, Victor S. Ndaw

Theses and Dissertations

TGFβ is involved in many pathological conditions, including autoimmune disorders, cancer, and cardiovascular and allergic diseases. We have previously found that TGFβ can suppress IgE-mediated mast cell activation in human and mouse mast cells in vitro. IL-33 is a recently discovered member of the IL-1 family capable of inducing mast cell responses and enhancing IgE-mediated activation. In this study, we investigated the effects of TGFβ on IL-33-mediated mast cell activation. Bone marrow-derived mast cells cultured in TGFβ -1, -2, or -3 showed reduced IL-33-mediated production of TNF, IL-6, IL-13 and MCP-1, in a concentration-dependent manner. Furthermore, TGFβ also reduced …

Low-Flow Domiciliary Oxygen As A Mechanism Of Ongoing Oxidative Stress In Copd Patients, Jill Stulce

Theses and Dissertations

Healthcare costs are escalating in the U.S., with a projected 48 trillion dollars by 2021. More than ever medical researches are obligated to ensure that costly treatment modalities are safe and effective. Chronic obstructive pulmonary disease (COPD) is a costly and debilitating disease, ranked as the third leading cause of death in America. Currently, treatment for COPD consists of anti-inflammatory agents, bronchodilators, antibiotics and supplemental oxygen when hypoxemia or clinical manifestations ensue. Oxidative stress is central to the pathology of COPD. Supplemental oxygen has been substantiated as an instigator of oxidative stress; however, LFDO has not been evaluated as a …

Evaluation Of Vaccination Policies Among Utah Pediatric Clinic Employees, Tia Peterson

Theses and Dissertations

Introduction: Pediatric health care settings are high risk environments for spreading communicable and vaccine preventable diseases from health care workers to susceptible patients. Methods: All managers of pediatric clinics operating in the state of Utah were included. Participants were invited to complete a two-page questionnaire regarding their clinic vaccination policies. Results: Half (n = 23, 50%) of Utah pediatric outpatient clinics recommend employee vaccinations, although employee refusal is allowed without consequence. Of all adult vaccines, influenza was most often included as part of the employee vaccination policy. Some clinics required unvaccinated employees to wear masks in the event of illness, …

Biginelli Synthesis And Characterization Of Potentially Anti-Proliferative Dihydropyrimidinone Thione Analogs, Timothy K. Summers

Theses and Dissertations

No abstract provided.

Factors Contributing To Attitudes Towards Disciplinary Parenting Styles, Amanda Marshall

Theses and Dissertations

The debate on whether or not corporal punishment is an acceptable method of discipline for children has been continuously researched and has consistently shown that the use of corporal punishment has a multitude of negative consequences on children (Gershoff, 2013). The present study aims to understand the factors which may contribute to the persistence of these supportive attitudes towards corporal punishment and abuse. The results of this study reveal that the age an individual becomes a parent/guardian is negatively correlated with their support for corporal punishment and acceptance of physical abuse. Strong correlations were also found between acceptance of abuse …

The Prevalence, Predictive Factors, And Classification Of Intrapulpal Cracks In Maxillary Premolars Requiring Endodontic Treatment, Sarah Krygowski

Theses and Dissertations

Cracked teeth may be difficult to diagnose. Craze lines rarely become symptomatic or require treatment. Cracks in the enamel and dentin alone may or may not become symptomatic and require restorative treatment. However, cracks extending into the enamel, dentin, and pulp chamber provide an avenue for bacteria to establish infection and this commonly results in symptoms and the need for endodontic and restorative treatment. The published endodontic literature has limited information regarding the prevalence or predictive factors for cracks extending into the pulp chamber of teeth. The purpose of this study was to determine the prevalence and classification of intrapulpal …

The Effect Of Statins On Il-33 Mediated Mast Cell Function, Marcela Taruselli

Theses and Dissertations

This study demonstrates original findings of statin effects on IL-33 stimulated mast cells. Statins are a class of drugs used to lower cholesterol production by targeting HMG CoA reductase. These commonly prescribed drugs have been shown to be immunomodulatory. In this study, we have found that pretreatment with statins has a variety of effects on IL-33 stimulated mast cells. Atorvastatin suppresses TNF and IL-6 production, while fluvastatin significantly enhances release of these proinflammatory cytokines in BMMCs. Although they have differing effects on cytokine production, both statins lowered ST2 expression on the cell surface, decreased cell viability, and enhanced expression of …