Gastrointestinal Microbiota Modulate Antinociceptive Tolerance Development In Mice With Chronic Morphine Exposure, Ryan A. Mischel

Theses and Dissertations

In October 2017, the United States government declared a state of public health emergency in response to the burgeoning prescription opioid epidemic. Opioid analgesics are the gold standard of therapy for moderate to severe pain, but their clinical utility is greatly limited by analgesic tolerance – a primary driver of diminished pain control and opioid dose escalations. Integral in this process are primary afferent sensory neurons in dorsal root ganglia (DRG), the first-order components of nociceptive sensation. With surmounting evidence that morphine and other narcotics can alter gut microbial composition and promote bacterial translocation to other tissues, a question arises …

The Periodontal Specialty: A Survey Regarding Our Future, John H. White

Theses and Dissertations

Purpose: To determine the characteristics influencing periodontal practices in Virginia and report on the anticipated changes in practice.

Methods: A REDCap survey was emailed to Virginia based American Academy of Periodontology (AAP) members assessing personal and practice demographics, trends in dental treatment and practice models, and how periodontists will adjust to account for these trends.

Results: The response rate was 31% (n=46). Respondents report greater referrals from more experienced general practitioners (GPs). Student debt was associated with age. Respondents ranked biologic advances, treatment of peri-implantitis, digital dentistry, development of corporate and group practice models, and GPs incorporating more periodontal …

A Comparison Of Quality Indicators Between Medicare Accountable Care Organizations And Health Maintenance Organizations Using Publicly Available Data, William W. Campbell Iii

Theses and Dissertations

The purpose of this study is to explore differences in quality between Medicare Accountable Care Organizations (ACO) and Health Maintenance Organizations (HMO). Three outcomes measures reported by these plans use different methodologies but possess enough alignment to permit comparison: percent of diabetic patients with last HbA1c > 9.0%, colon cancer screening rate and ER visits per 1,000. These outcomes are the dependent variables (DV). A secondary purpose is to explore differences in quality based on the size of the beneficiary population served, using the same measures.

As the Medicare program faces threats to its solvency in coming decades, with 10,000 baby …

A Comparison Of The Antimicrobial Efficacy Of Silver Diamine Fluoride And Silver Nitrate: An In Vitro Study, Nicholas L. Luke

Theses and Dissertations

A COMPARISON OF THE ANTIMICROBIAL EFFICACY OF SILVER DIAMINE FLUORIDE AND SILVER NITRATE: AN IN VITRO STUDY

By: Nicholas L Luke, 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, May 2018

Thesis Advisor: William O. Dahlke Jr., D.M.D.

Pediatric Dentistry, Department Chair

Purpose: To determine the antimicrobial efficacy of SDF and SN/NaF.

Methods: Three bacterial species were combined to create an in vitro biofilm. Treatment was completed with SN, SN/NaF, SDF, SDF½ or untreated (control).

Results: The untreated group demonstrated significantly higher …

Prevalence And Factors Of Sibling-Recurrent Dental Treatment Under General Anesthesia, Brandy N. Edmonds

Theses and Dissertations

Objective/Aims: Assess the prevalence of sibling recurrent dental general anesthesia (DGA) at VCU Pediatric Dentistry. Assess factors that contribute to sibling recurrent dental general anesthesia. Methods: The guardian of patients with siblings were provided a questionnaire to assess the prevalence and factors associated with recurrent DGA. Results: A total of 40 families with a child presenting for GA and at least one sibling were included in the study. Of these, 45% had sibling-recurrent GA treatment (20% in one sibling; 25% in 2 or more siblings). Additionally, 13% of the children currently presenting for GA had already been treated under GA, …

Assessment Of Pediatric-Focused Brief Motivational Interviewing Training Of Dental Students And Pediatric Dental Residents, Victoria M. Onesty

Theses and Dissertations

Purpose: To assess dental students and pediatric dental residents’ knowledge and attitudes towards motivational interviewing and evaluate the efficacy of a pediatric-focused brief motivational interviewing training program.

Methods: A total of 66 participants were enrolled; 35% were third year dental students, 46% were fourth year dental students and 18% were pediatric dental residents. Participants completed three questionnaires: the first before the training, the second immediately after the training and the third approximately 3.5 months after the training.

Results: A significant increase in correct responses was found for 4 of the 5 questions assessing participants’ knowledge. Participants were satisfied with the …

Metabotropic Glutamate Receptor 2 Activation: Computational Predictions And Experimental Validation, Amr Ellaithy

Theses and Dissertations

G protein-coupled receptors (GPCRs) are the largest family of signaling proteins in animals and represent the largest family of druggable targets in the human genome. Therefore, it is of no surprise that the molecular mechanisms of GPCR activation and signal transduction have attracted close attention for the past few decades. Several stabilizing interactions within the GPCR transmembrane (TM) domain helices regulate receptor activation. An example is a salt bridge between 2 highly conserved amino acids at the bottom of TM3 and TM6 that has been characterized for a large number of GPCRs. Through structural modeling and molecular dynamics (MD) simulations, …

The Influence Of Clinically Meaningful Factors On The Performance Of The Recommended Annual Diabetic Foot Screening, Trisha A. Sando

Theses and Dissertations

Background: Diabetic foot ulcers are the result of multiple complications from hyperglycemia and lead to poor quality of life and high healthcare costs. The annual diabetes foot screening exam (ADFSE) and prevention interventions can reduce DFUs up to 75%. In 2015, 71% of the US population received the ADFSE.

Objectives: The main objectives of this dissertation were: 1) to determine the association between adherence to diabetes self-management behaviors and the ADFSE, 2) to determine the association between concordant and discordant comorbidities and the ADFSE and 3) to determine the association between the performance of diabetes preventive care processes, number of …

Queer Health Equity And Cervical Cancer: Identifying Social Determinants Of Papanicolaou Test Uptake In A Sample Of Sexual Minority Women And Gender Nonbinary Individuals, Ariella R. Tabaac

Theses and Dissertations

Sexual minority women (SMW) demonstrate lower rates of cervical cancer screening than heterosexual women. This is concerning as lesbian and bisexual women tend to engage in higher rates of substance-related cancer risk behaviors, unprotected sex, and tend to have higher body mass indices, all of which are risk factors for cancer development. Another major risk factor, screening avoidance, places SMW at increased risk for the development of high grade cervical lesions in the absence of early detection practices, which is likely to impact overall cervical cancer morbidity in this population. The aim of the present study was to utilize the …

Comparison Of Hiring Strategies Of Orthodontic Private Practitioners, Steven C. Petritz

Theses and Dissertations

COMPARISON OF HIRING STRATEGIES OF ORTHODONTIC PRIVATE PRACTITIONERS

By Steven C. Petritz, 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, 2018

Thesis Director: Bhavna Shroff, D.D.S., M.Dent.Sc., M.P.A.

Virginia Commonwealth University Department of Orthodontics Program Director

Purpose: Evaluate factors that influence hiring outcomes of clinical and non-clinical staff in orthodontic private practices.

Methods: Orthodontists (n=1968) were surveyed regarding their hiring methods and outcomes. Responses were summarized using descriptive statistics. Chi-square tests were used to compare between hiring strategies and outcomes. …

Evaluation Of Fit For 3d Printed Retainers As Compared To Thermoform Retainers, David J. Cole

Theses and Dissertations

ABSTRACT

EVALUATION OF FIT FOR 3D PRINTED RETAINERS AS COMPARED TO THERMOFORM RETAINERS

By David Cole, D.M.D.

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

Thesis Directors: Eser Tüfekçi, D.D.S., M.S., Ph.D., M.S.H.A.

Professor, Department of Orthodontics

Sompop Bencharit, D.D.S., M.S., Ph.D.

Associate Professor and Director of Digital Dentistry, Department of General Practice

Introduction: Despite recent advances in three-dimensional (3D) printing, little information is available on 3D printed retainers

Methods: Three reference models were used to fabricate traditional vacuum formed, commercially-available vacuum formed, and 3D printed …

Potential Antimicrobial Methods For Provisionalizing Teeth After Endodontic Treatment, Laura T. Garden

Theses and Dissertations

POTENTIAL ANTIMICROBIAL METHODS FOR PROVISIONALIZING TEETH AFTER ENDODONTIC TREATMENT

By Laura T. Garden, DDS

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, 2018

Thesis Advisor: Garry Myers, DDS

Department of Endodontics

Objective:To evaluate the effectiveness of a Chlorhexidine soaked cotton pellet on bacterial leakage.

Methods: Fifty-one extracted teeth, including six controls, were instrumented, obturated, and sealed with either a cotton pellet (CP), 2% Chlorhexidine soaked cotton pellet (CHX), or a Permaflo orifice barrier (OB). Each root was suspended between two chambers: the …

Orthodontists’ And Patients’ Preferences In Website Design In The Selection Of An Orthodontic Practice: A Comparative Study, Taylor R. Brown

Theses and Dissertations

Objective: To determine which website characteristics are preferred by orthodontists, adult patients, and parents of patients.

Materials and Methods: 1,000 active members of the American Association of Orthodontists and 750 active orthodontic patients/parents were sampled. Participants rated the importance of website characteristics, indicated presence of those characteristics on the current website, and ranked sample website images. Preferences were compared between orthodontist and the patient/parent group using t-tests and sample websites were compared using ANOVA models and Tukey’s adjusted post-hoc tests. Significance level was set at 0.05.

Results: 11 of the 16 website features showed significant differences between patients/parents and orthodontists. …

Change In Working Length At Different Stages Of Instrumentation As A Function Of Canal Curvature, Mei Tang

Theses and Dissertations

The aim of this study was to determine the change in working length (∆WL) before and after coronal flaring and after complete rotary instrumentation as a function of canal curvature. One mesiobuccal or mesiolingual canal from each of 43 extracted molars had coronal standardization and access performed. Once the access was completed, canal preparation was accomplished using Gates Glidden drills for coronal flaring and EndoSequence files for rotary instrumentation. WLs were obtained at 3 time points: pre-instrumentation (unflared), mid-instrumentation (flared) and post-instrumentation (concluded). Measurements were made via direct visualization (DV) and the CanalPro apex locator (EM) in triplicate by a …

The Contribution Of Sarm1 To Axonal Degeneration In Cns Inflammatory Disorders, Daniel C. Njoku

Theses and Dissertations

BACKGROUND: Multiple sclerosis (MS) is an inflammatory disease of the central nervous system (CNS) that results in demyelination and axonal loss. Efficiently targeting mechanisms of axonal degeneration in MS has the potential to reduce disability but remains an unmet need. Prior research has identified the protein sterile alpha and TIR motif containing 1 (SARM1) as a critical factor that promotes axonal destruction in the program of axonal degeneration known as Wallerian degeneration. SARM1 inactivation reduces axonal degeneration in a variety of contexts including traumatic and toxic injury, but it remains unknown to what extent SARM1 is involved in axonal degeneration …

The Effects Of Amixicile On Sub-Gingival Biofilm Cultured From Humans, Kian Azarnoush

Theses and Dissertations

Periodontitis is an inflammatory disease of the oral cavity induced by anaerobic bacteria, that remains to be the primary cause of tooth loss in adults worldwide. Finding an anti-microbial therapeutic to selectively target periodontal pathogens has proven to be difficult, and current treatment modalities only provide a transient benefit. Amixicile is a non-toxic, readily bioavailable novel antimicrobial that targets strict anaerobes through inhibition of the activity of Pyruvate Ferredoxin Oxidoreductase (PFOR), a major enzyme mediating oxidative decarboxylation of pyruvate, a critical step in metabolism. Our study aimed to evaluate the efficacy of amixicile in inhibiting the growth of bacteria harvested …

Observations Of Trends And Successes Of Revascularization Therapy At Virginia Commonwealth University: A Retrospective Study, Richard W. Sedwick

Theses and Dissertations

The aim of this study was to determine the trends in protocol, success rates, and consistency in follow up of revascularization procedures in a controlled environment. Patients of the Virginia Commonwealth University School of Dentistry were identified who were offered revascularization therapy as a treatment option on immature permanent teeth from January 1, 2010 to May 31, 2017. A total of 77 patients and 78 teeth were evaluated for revascularization therapy. For patients accepting treatment, records were reviewed for outcome assessment and consistency of follow up. A total of 30 patients (31 teeth) were treated following revascularization protocols, with only …

Biochemical Analysis Of Putative Rna-Binding Proteins In Porphyromonas Gingivalis, Jacob Mirpanah

Theses and Dissertations

BIOCHEMICAL ANALYSIS OF PUTATIVE RNA-BINDING PROTEINS IN PORPHYROMONAS GINGIVALIS

By Jacob Mirpanah

Bachelor of Arts in Biology, University of Virginia, 2015

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

Virginia Commonwealth University, 2018

Major Director: Janina P. Lewis, Ph.D., Philips Institute for Oral Health Research

RNA-Binding Proteins (RBPs) play important regulatory roles in countless cellular processes. Often via the induction of a structural change in RNA’s secondary structure, RBPs are known to modulate protein expression through post-transcriptional regulation. In Escherichia coli, such RBPs have …

Bromodomain And Extraterminal Domain (Bet) Inhibitor Rvx-208 Ameliorates Periodontal Bone Loss, Nicholas J. Clayton

Theses and Dissertations

Periodontal disease affects 47% of Americans over 30 and is a growing global concern. Current treatments for periodontal disease focus on the mechanical elimination of periodontal biofilms. Very few treatments are available that target the rampant, unregulated host immune response that is ultimately responsible for tissue degradation. BET proteins have been shown to play critical roles in inflammatory gene regulation and are therefore potentially ideal therapeutic targets for treating periodontal disease. RVX-208 is a selective BET-inhibitor with a high affinity for Bromodomain 2 (BD2) as compared to BD1 in BET proteins. Our previous studies have shown that RVX-208 inhibits inflammatory …

The Role Of A Type Lamins In Regulating Myelination, Jacqueline M. Deloyht

Theses and Dissertations

Multiple sclerosis (MS), a demyelinating disorder of the central nervous system (CNS), affects approximately 400,000 individuals in the United States, and 2.5 million people worldwide. It is a leading cause of disability in young adults. Current treatments for MS target the inflammatory aspects of the disease, but do not aid in remyelination. To address remyelination as a therapeutic strategy, it is imperative to identify mechanisms that regulate myelin formation, including epigenetic targets. In this study, we investigate the role of the LMNA, a gene encoding Lamins A and C, intermediate filaments of the nuclear lamina, in regulating oligodendrocyte development and …

Effects Of The Na-Cl Co-Transporter (Ncc) In Western Diet Induced Metabolic And Cardiac Dysfunction, Zachary S. Cutter

Theses and Dissertations

Interleukin-18 (IL-18) is a pro-inflammatory cytokine known to be involved in maintaining metabolic homeostasis; however, also capable of inducing cardiac dysfunction. Additionally, IL-18, has been shown to bind to a novel receptor, the Na-Cl Co-transporter (NCC). We hypothesized that NCC mediates IL-18 metabolic and cardiac signaling in mice. Using male C57BL/6J mice, we compared the metabolic and cardiac function changes after at least 8 weeks of high-saturated fat high sugar diet (Western Diet) in NCC knockout (NCCKO), IL-18 knockout (IL-18KO), and wild-type mice. We show that NCCKO mice have significantly increased body weight gain from baseline, no difference in fasting …

Investigating Smoke Exposure And Chronic Obstructive Pulmonary Disease (Copd) With A Calibrated Agent Based Model (Abm) Of In Vitro Fibroblast Wound Healing., James A. Ratti

Theses and Dissertations

COPD is characterized by tissue inflammation and impaired remodeling that suggests fibroblast maintenance of structural homeostasis is dysregulated. Thus, we performed in vitro wound healing experiments on normal and diseased human lung fibroblasts and developed an ABM of fibroblasts closing a scratched monolayer using NetLogo to evaluate differences due to COPD or cigarette smoke condensate exposure. This ABM consists of a rule-set governing the healing response, accounting for cell migration, proliferation, death, activation and senescence rates; along with the effects of heterogeneous activation, phenotypic changes, serum deprivation and exposure to cigarette smoke condensate or bFGF. Simulations were performed to calibrate …

Advances In Dual-Energy Computed Tomography Imaging Of Radiological Properties, Dong Han

Theses and Dissertations

Dual-energy computed tomography (DECT) has shown great potential in the reduction of uncertainties of proton ranges and low energy photon cross section estimation used in radiation therapy planning. The work presented herein investigated three contributions for advancing DECT applications. 1) A linear and separable two-parameter DECT, the basis vector model (BVM) was used to estimate proton stopping power. Compared to other nonlinear two-parameter models in the literature, the BVM model shows a comparable accuracy achieved for typical human tissues. This model outperforms other nonlinear models in estimations of linear attenuation coefficients. This is the first study to clearly illustrate the …

Rational Design Of Allosteric Modulators Of Hemoglobin As Dual Acting Antisickling Agents, Piyusha P. Pagare

Theses and Dissertations

Intracellular polymerization of deoxygenated sickle hemoglobin (Hb S) remains the principal cause of the pathophysiology associated with sickle cell disease (SCD). Naturally occurring and synthetic allosteric effectors of hemoglobin (AEH) have been investigated as potential therapeutic agents for the treatment of SCD. Several aromatic aldehydes, including vanillin, have been studied previously as AEHs for their antisickling activities. Specifically, these compounds form Schiff- base adduct with Hb to stabilize the oxygenated (R) state, increase Hb affinity for O2 and concomitantly prevent the hypoxia-induced primary pathophysiology of Hb S polymerization and RBC sickling, in turn, ameliorating several of the cascading secondary adverse …

Heparan Sulfate, A New Target For Platinum In Metastatic Tnbc, Samantha J. Katner

Theses and Dissertations

Abstract

Heparan Sulfate, A New Target for Platinum in Metastatic TNBC

Author: Samantha J. Katner, Ph.D.

A dissertation submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy

Virginia Commonwealth University, 2018

Advisor: Dr. Nicholas Farrell, Professor, Chemistry Department

Heparan sulfate proteoglycans (HSPGs), composed of the linear polysaccharide heparan sulfate (HS) conjugated to a protein core, are located on the cell surface and extracellular matrix. The HS chains display varying degrees of sulfation, which constitutes the molecular recognition motif for many HS-protein interactions. HSPGs, associated growth factors, and heparanase promote tumor progression by facilitating invasion, angiogenesis, …

Development And Validation Of A Semi-Physiological Pharmacokinetic (Pbpk) Model To Predict Systemic And Pulmonary Exposures After Intravenous, Oral Administration And Pulmonary Inhalation Of Selected Drugs, Budesonide, Tobramycin And Ciprofloxacin, In Humans, Bishoy Hanna

Theses and Dissertations

Using a semi-PBPK modeling/quantitative meta-analysis approach, this project investigated what factors affect pulmonary and systemic exposures of Budesonide (BUD), Tobramycin (TOB), and Ciprofloxacin (CIP) after inhalation:

Three structurally different pulmonary disposition models were developed for each drug, including pulmonary absorption (all three), excretion (TOB and CIP) and sequestration (TOB) in a peripheral and central lung compartment. Systemic disposition parameters were estimated using available human mean plasma (c_p(t)) and sputum (c_s(t)) concentration profiles after IV administration, and GI absorption parameters were estimated from these profiles after oral administration. Pulmonary disposition parameters were estimated from c_p(t) …

Nuclear Rupture In Progeria Expressing Cells, Kranthidhar Bathula

Theses and Dissertations

Cells regularly take on various types of force in the body. They have structures that are able to mediate, transfer and respond to the forces. A mutation in force regulating proteins such as lamin in the nucleus or the KASH domain which connects the nucleus to the cytoskeleton of the cell can cause catastrophic events to occur. The aims of this study were to better understand the response of the nucleus when structural proteins are mutated or are not present while under force. Progeria, a rare disease where an additional farnesyl group is attached to lamin was used in this …

Enhancing Adherence To Prescribed Opioids Using A Mobile-Base Application: A Pilot Study Of Feasibility In Chronic Non-Cancer Pain, Daniel M. Sop

Theses and Dissertations

In this study we present feasibility of a mobile monitoring and reporting system that would provide an accurate unbiased screening tool to systematically analyze opioid adherence in Sickle cell disease patients. In addition, the software simultaneously measures pain. The Mobile Applications Rating Scale: a new and validated tool for assessing the quality of health mobile apps for engagement, functionality, aesthetics, information quality, subjective quality, relevance and overall impact was administered post usage to evaluate the application.

A total of 28 patients were recruited to review and test the software at one sitting. The majority of the population found the application …

Understanding The Role Of Phosphoinositide 3-Kinase And Its Function As A Driving Force Behind The Er Stress Response In Fibrostenotic Crohn’S Disease-Affected Ileal Smooth Muscle Cells, Prashant Yadav

Theses and Dissertations

Crohn’s disease (CD) affects about 780,000 people in the United States alone, and it is estimated that 6-15 per 100,000 persons will receive a diagnosis of this disease each year. There currently is no cure for Crohn’s disease, and available medical therapies simply serve to alleviate the inflammation. This does not help treat fibrostenosis that Crohn’s disease patients may develop, which can only be treated surgically. Finding alternatives to treat CD requires an understanding of mechanisms at the biochemical level. In this thesis, we attempted to gain a better understanding of certain pathways found to be active in Crohn’s disease-affected …

Advanced Imaging Analysis For Predicting Tumor Response And Improving Contour Delineation Uncertainty, Rebecca N. Mahon

Theses and Dissertations

ADVANCED IMAGING ANALYSIS FOR PREDICTING TUMOR RESPONSE AND IMPROVING CONTOUR DELINEATION UNCERTAINTY

By Rebecca Nichole Mahon, MS

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

Virginia Commonwealth University, 2018

Major Director: Dr. Elisabeth Weiss,

Professor,

Department of Radiation Oncology

Radiomics, an advanced form of imaging analysis, is a growing field of interest in medicine. Radiomics seeks to extract quantitative information from images through use of computer vision techniques to assist in improving treatment. Early prediction of treatment response is one way of improving overall patient care. This work …