The Characterization Of A Putative Virulence Factor Expressed By Sneathia Amnii, Amy Sanford

Theses and Dissertations

Preterm birth, defined at birth before 37 weeks gestation, affects millions of newborns worldwide every year. Preterm birth is a leading cause of infant morbidity and mortality. One major cause of preterm birth is preterm premature rupture of membranes (PPROM), which can be triggered by bacterial infection and inflammation. A bacterial species that has been implicated in preterm birth and other obstetric complications is Sneathia amnii. The goals of this study were to observe cytopathogenic effects caused by S. amnii strain Sn35 and identify putative virulence factors causing those effects. Sn35 was able to adhere to, invade, and damage/kill …

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 …

Computational Modeling To Assess Surgical Procedures For The Treatment Of Adult Acquired Flatfoot Deformity, Brian A. Smith

Theses and Dissertations

Several surgically corrective procedures are considered to treat Adult Acquired Flatfoot Deformity (AAFD) patients, relieve pain, and restore function. Procedure selection is based on best practices and surgeon preference. Recent research created patient specific models of Adult Acquired Flatfoot Deformity (AAFD) to explore their predictive capabilities and examine effectiveness of the surgical procedure used to treat the deformity. The models’ behavior was governed solely by patient bodyweight, soft tissue constraints, and joint contact without the assumption of idealized joints. The current work expanded those models to determine if an alternate procedure would be more effective for the individual. These procedures …

The Role Of Α3Β4* Subtype Of Nicotinic Acetylcholine Receptors In Reversing Opioid-Induced Constipation In Mice, Aravind Gade

Theses and Dissertations

Opioids are excellent pain relievers. A major side-effect of chronic opioid treatment is constipation whereas withdrawal following chronic exposure leads to diarrhea and increased gastrointestinal motility. These effects of chronic opioids are mediated by μ-opioid receptors expressed on enteric neurons. Previous studies have shown that chronic opioids enhance sensitivity to nicotine in the gastrointestinal tract. This suggested that prokinetic effects of nicotine mediated through the activation of nicotinic acetylcholine receptors (nAChRs) may be useful in reversing opioid-induced constipation. The goal of this dissertation was to investigate the nAChR subtype expressed on enteric neurons and their role in reversing opioid-induced constipation. …

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 …

Psychoactive Synthetic Cathinones (Or 'Bath Salts'): Investigation Of Mechanisms Of Action, Farhana Sakloth

Theses and Dissertations

Synthetic cathinones represent threatening and high abuse-potential designer drugs. These are analogs of cathinone (the b-keto analog of amphetamine (AMPH)) a naturally occurring stimulant found in the plant Catha Edulis. Methcathinone (MCAT) was the first synthetic analog of cathinone to be identified in 1987 by Glennon and co-workers and it exerted its action primarily through the dopamine transporter (DAT). Most central stimulants exert their action via monomaine transporters by causing either the release (e.g. cathinone analogs such as MCAT) or by preventing the reuptake (e.g. cocaine) of the neurotransmitter dopamine (DA) thus increasing the extracellular synaptosomal concentration of this …

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 …

Factors That Influence Breast Cancer Diagnoses In Virginia Women 40-64 Years Old Who Utlized The Every Woman’S Life Program 1998-2012, Melanie C. Dempsey

Theses and Dissertations

This dissertation examines sociodemographic determinants and preventive health behaviors among women 40-64 years of age who participated in the Virginia Department of Health’s Every Woman’s Life breast cancer screening program. Utilizing secondary data, this research sought to explore patterns of breast cancer incidence, mammography screening utilization and sources of health information among low-income women.

The Virginia Department of Health provided a large sample size (N=34,942) on which to perform binary logistic regression analyses. Sociodemographic determinants and preventive health behaviors were analyzed as potential influencing factors in the diagnosis of breast cancer, the stage at the time of diagnosis and source …

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 …

Individuals With Fetal Alcohol Spectrum Disorder: Predictive Factors For Successful Occupational Performance, Mary Culshaw

Theses and Dissertations

As awareness and diagnoses of FASD grow in Canada, there is increased need to support these individuals across their lifespan. One study suggested the prevalence of FASD may be as high as 10 per 1000 births (May & Gossage, 2001). The impact to society is growing as well, since this population requires support across their lifespan due to cognitive and sometimes physical impairments. It was estimated that the annual cost to Canadians was $53 billion (in 2007 dollar value) to support individuals aged 0-53 years (Stade et al., 2009). There is mounting evidence identifying the cognitive and physical impairments that …

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 …

Vitamin C: A Potential Regulator Of Inflammatory Response, Bassem M. Mohammed

Theses and Dissertations

Introduction: Neutrophils (PMNs) and Macrophages are the first responders recruited consecutively to the site of injury/inflammation. PMNs’ response/fate as well as macrophage reprogramming ultimately determine the course of resolution of inflammation. Physiologic wound healing has a significant inflammatory component. An exaggerated inflammation however is self-defeating leading to delayed healing. Parenteral vitamin C (VitC) attenuated inflammation in murine sepsis models and in patients with sepsis. However information about the mechanisms by which VitC regulates these events is limited.

Methods: Humanized mice lacking VitC synthesis capability (Gulo^-/-) were used. VitC sufficient and deficient mice were challenged with sterile inflammation, or …

Chronic Behavioral And Cognitive Deficits In A Rat Survival Model Of Organophosphate Toxicity, Beverly Huang

Theses and Dissertations

Organophosphates (OPs) are a major class of pesticides and nerve agents that elicit acute toxicity by inhibiting acetylcholinesterase (AChE), the enzyme responsible for the degradation of the neurotransmitter acetylcholine in the central and peripheral nervous systems. Acetylcholine accumulation following extensive AChE inhibition leads to an acute cholinergic syndrome characterized by autonomic dysfunction, involuntary movements, muscle fasciculations, respiratory distress, and seizures. Despite their classification as moderate to highly toxic, OP pesticides are the most widely used class of insecticides in the U.S., and are even more commonly used worldwide. Additionally, there is a growing concern that OP nerve agents could be …

Esthetic Preferences Of Maxillary Incisor Labiolingual Inclination Across Races, Elvi M. Barcoma

Theses and Dissertations

Abstract

ESTHETIC PREFERENCES FOR MAXILLARY INCISOR LABIOLINGUAL INCLINATION ACROSS RACES

by Elvi Marie Barcoma, 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

Major Director: Bhavna Shroff, D.M.D., M.Dent.Sc, Program Director, Orthodontics

Objective: To determine if people of different racial backgrounds prefer different amounts of

maxillary incisor labiolingual inclination from a smiling profile view.

Materials and Methods: An electronic survey was created with smiling profile images of an African-American female and a White female with varying degrees of maxillary incisor labiolingual inclination. …

Restorative Characteristics Of Intrapulpally Cracked Teeth, Charles M. Beavers

Theses and Dissertations

Cracked teeth have long presented a diagnostic challenge. Previous investigators have considered possible predictive factors, many of which revolve around the tooth’s restorative characteristics. Few have investigated the restorative status of teeth with cracks extending into the pulp chamber. The purpose of this investigation was to determine the prevalence of the different types of restorations present in intrapulpally cracked teeth and determine any other restorative factors that may aid in predicting the presence or extent of an intrapulpal crack. Intrapulpally cracked molars requiring endodontic therapy at the VCU Graduate Endodontic Practice were included in this study. For each tooth, the …

In-Vitro Assessment Of A Novel Bracket's Effect On Resistance To Sliding, James Blackburn

Theses and Dissertations

Friction, binding and notching are the factors that contribute to resistance to sliding during orthodontic tooth movement. However, most attempts at reducing resistance aim only to reduce the archwire/ligature friction. In this study, a novel bracket with a unique design aimed to reduce all three components of resistance to sliding. Four types of brackets (passive and active self-ligating, traditionally ligated and the novel bracket, (n=5, each) were tested at 0, 2, 4, 6, and 8ᵒ of tip on a 0.019 x 0.025”archwire. The resistance to sliding values were recorded. At 0ᵒ, the passive self-ligating and novel bracket showed reduced resistance …

Treatment Decisions Involving Teeth With Intrapulpal Cracks: A Survey Of Endodontists, Sheldon M. Sealey

Theses and Dissertations

There is no universal protocol for diagnosing, treating and managing cracked teeth. The purpose of this survey was to investigate the use of traditional methods of crack detection and to explore how treatment decisions were made using an intrapulpal crack classification. The electronic survey was sent to 1115 active members of the American Association of Endodontists (AAE) and The Digital Office (TDO^™) community. Comparisons were assessed using logistic or repeated-measures regression. The most often used diagnostic method was probing. When the crack involved one wall, 85% of respondents would complete root canal therapy > 50% of the time or …

Peracetic Acid: A Practical Agent For Sterilizing Heat-Labile Polymeric Tissue-Engineering Scaffolds, William R. Trahan

Theses and Dissertations

Advanced biomaterials and sophisticated processing technologies aim to fabricate tissue-engineering scaffolds that can predictably interact within a biological environment at a cellular level. Sterilization of such scaffolds is at the core of patient safety and is an important regulatory issue that needs to be addressed prior to clinical translation. In addition, it is crucial that meticulously engineered micro- and nano- structures are preserved after sterilization. Conventional sterilization methods involving heat, steam and radiation are not compatible with engineered polymeric systems because of scaffold degradation and loss of architecture. Using electrospun scaffolds made from polycaprolactone (PCL), a low melting polymer, and …

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 …

Restoring Lateral Incisors And Orthodontic Treatment: Perceptions Among General Dentists And Othodontists, Matthew A. Sandretti, Bhavna Shroff, Steven J. Lindauer, Al M. Best

Theses and Dissertations

The purpose of this study was to identify and compare preferences and perceptions of orthodontists and general dentists when restoring peg-shaped lateral incisors. The investigation sought to summarize these preferences with regard to treatment planning, tooth preparation and interdisciplinary communication. A pair of mailed and electronic surveys was distributed to 1,500 general dentists and orthodontists, respectively. The results indicated that general dentists perceived that general dentists held the primary decision-making responsibility, while orthodontists disagreed (P<0.0001). Orthodontists prioritized the treatment goals of Class I canine relationship and overbite/overjet more significantly than general dentists, whom valued tooth proportions more highly (P<0.0001). General dentists reported receiving significantly less input than orthodontists report seeking (P<0.0001).The consensus of both groups showed that the tooth should be positioned centered mesiodistally and guided by the gingival margins incisogingivally. Both groups agree that orthodontists must improve communication to improve treatment results.

Examination Of Lower Extremity Mechanics During Three Landing Tasks And Injury Prediction Ability Of Those Models As Compared To A Functional Test, Timothy G. Coffey

Theses and Dissertations

Anterior cruciate ligament (ACL) ruptures are one of the most common knee ligament injuries suffered by both male and female athletes. These injuries are severe in nature and also have long-term impacts on activities of daily living. Significant research has been conducted utilizing a drop landing task to attempt to better understand the mechanics behind the injury and to help identify at-risk athletes for targeted intervention. However, there have not been any published standards for the height of the drop landing activity, and previous researchers have also raised some concerns about the ability of a drop landing task to replicate …

A Study Of Errors For 4d Lung Dose Calculation, Nahla K. Sayah

Theses and Dissertations

To estimate the delivered dose to the patient during intra-fraction or throughout the whole treatment, it is important to determine the contribution of dose accumulated at different patient geometries to the overall dose. Dose mapping utilizes deformable image registration to map doses deposited on patient geometries at different times. Inputs to the dose mapping process are the irradiated and reference images, the displacement vector field, and a dose mapping algorithm. Thus accuracy of the mapped dose depends on the DVF and dose mapping algorithm. Dose mapping had been the subject of many research studies however, up to now there is …

General Dentists' Role In Providing Care To Very Young Children:Pediatric Dentists' Perspective, Shinjni Razdan

Theses and Dissertations

To examine the pediatric dentists’ perspective on level of care to children 0-3 years old by general dentists, an electronic survey was sent out to 5185 AAPD members and 769 responded (response rate: 14.8%). Forty-six percent agreed with a general dentist providing a dental home to children 0-3 years old. Only 24% agreed that general dentists could perform complex restorative and behavior management procedures for 0-3 years old. Younger respondents, pediatric dentists who practice in rural areas or teaching pediatric dentistry, and those who perceived adequate exposure during dental school were more likely to agree on general dentists proving a …

The Effectiveness Of A Preventive Recall Strategy In Children Following Dental Rehabilitation Under General Anesthesia, Katherine A. Nordeen

Theses and Dissertations

Purpose: This was a pilot study to assess the impact of a preventive strategy following full-mouth dental rehabilitation (FMDR) under general anesthesia in children with early childhood dental caries.

Methods: Sixty-six patients completed FMDR and were included in the analysis. At the consultation visit, caries risk assessment (CRA) and dental exam information were recorded, and caregivers completed an oral health knowledge (OHK) questionnaire. Patients returned for a post-surgery and recall visit. Caregivers received oral hygiene instructions in a motivational-interviewing style.

Results:At the consultation visit all patients were high risk. At the post-surgery visit, only 47% remained high risk …

Characterization Of Leukocyte-Platelet Rich Fibrin, A Novel Biomaterial, Fadi K. Hasan

Theses and Dissertations

Autologous platelet concentrates represent promising innovative tools in the field of regenerative medicine and are successfully used in oral surgery. Several commercial systems exist that generate various forms of platelet concentrates including Platelet-rich plasma (PRP) and Platelet-rich fibrin (PRF). The alpha- granules of entrapped platelets release a variety of peptide growth factors that promotes healing. Usually PRP is a suspension that can be injected into the site of injury or used as a gel with the addition of thrombin (PRP-gel). In contrast Choukroun’s L-PRF is a dense fibrin based biomaterial enriched with platelets and growth factors. The physical state of …

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 …

The Role Of Noxa/Mcl-1 In Head And Neck Squamous Cell Carcinoma (Hnscc) Treatment, June Young Lee

Theses and Dissertations

Head and neck cancer is the sixth leading type of cancer with 90 percent of head and neck cancer arising from squamous cell lining on the epithelium of the oral and nasal cavity, pharynx, and salivary gland. Even with tremendous achievements on chemotherapeutic drugs and therapies, the long-term prognosis of patients with advanced head and neck squamous cell carcinoma (HNSCC) has shown little improvement over the last three decades. Cisplatin is one of widely used chemotherapeutic drugs for multiple

cancers, including head and neck cancer, but the prolonged use of this drug is limited by its toxicity and by the …

Improving Understanding Of Colorectal Cancer Screening Decisional Conflict And Breast Cancer Survivorship Care, Kara P. Wiseman

Theses and Dissertations

Background: Behavioral interventions and evidence based guidelines along the cancer control continuum can reduce the burden of cancer.

Objectives: This dissertation aims to increase our understanding of colorectal cancer screening (CRCS) decisional conflict and breast cancer survivorship care. This project: 1) assesses CRCS decisional conflict in a general population, 2) uses the Theory of Triadic Influence to model and evaluate direct and indirect associations between CRCS decisional conflict and colonoscopy adherence, 3) assesses post-treatment breast cancer care.

Methods: Data from a questionnaire administered to randomly selected adults, 50-75 years, living in six MN communities (N=1,268) and the 2010 Behavioral Risk …

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. …

Identification Of Candidate Genes For Craniosynostosis, Karen Rymer

Theses and Dissertations

Craniosynostosis is a disorder characterized by the premature fusing of cranial sutures in an infant. Premature closure of these sutures can lead to detrimental consequences on the development of a child. The two broad categories of craniosynostosis are classified as syndromic and nonsyndromic. Nonsyndromic craniosynostosis involves only the fusion of one or more sutures, whereas syndromic craniosynostosis involves other abnormalities throughout the body of the affected individual. Two of the families analyzed in this study were of the syndromic nature, and known FGFR mutations were discovered. However, phenotypical features documented in association with these mutations differed from our individuals. Two …