Stat5a Regulation By Serine Phosphorylation In Breast Cancer, Alicia E. Woock

Theses and Dissertations

The neuroendocrine hormone prolactin (PRL) and its cognate receptor (PRLr) have been implicated in the pathogenesis of breast cancer. PRL signaling relies on activating kinases such as the tyrosine kinase Jak2 and serine/threonine kinases ERK1/2, NEK3, PI3K, and AKT. In the canonical pathway of PRL signaling, JAK2 phosphorylates the transcription factor STAT5a at tyrosine residue 694 (pY694-STAT5a), preceding STAT5a nuclear translocation and transcriptional activity. However, STAT5a exists with functional duality as a transcription factor, having both pro-differentiative and pro-proliferative target genes. Other STAT family members (STATs 1, 3, and 6) have been shown to have transcriptional activity in the un-tyrosine-phosphorylated …

Influence Of Metal Sleeves In The Accuracy Of Dental Implant Placement Using Guided Implant Surgery, Coleman Adams

Theses and Dissertations

The fabrication of implant surgical guides through stereolithographic 3D printing has become a staple in dental implant guided surgery over the last couple decades. These surgical guides have typically utilized metal sleeves to assist in guidance of the drills during osteotome preparation. The metal sleeves can be costly and potentially cause deviations if improperly placed during post-processing of the guide. This research explored a novel method for the utilization of sleeve-free surgical guides by comparing the dimensional and angulational deviations between the implant guides with and without a metal sleeve. To achieve this goal, two separate aims were pursued. Our …

Exploring The Dopamine Transporter Utilizing A Two-Pronged Approach With Novel Cathinone Analogs And Mutant Dopamine Transporters, Charles B. Jones Iii

Theses and Dissertations

The dopamine transporter (DAT) is responsible for the removal of the neurotransmitter from the synaptic gap and a therapeutic target for a multitude of drugs. While the ortholog Drosophila melanogaster dopamine transporter (dDAT) and human serotonin transporter (hSERT) have resolved structures, the human dopamine transporter (hDAT) does not. A 3-D computational homology model of hDAT was constructed for the study of molecular interactions with agents within the central binding site (S1) of the transporter.

Synthetic cathiones are a class of abused stimulant drugs that primarily target DAT. Greater than 150 cathinones have been identified on the clandestine market but there …

Knowledge, Perception, And Clinical Management Strategies Of Us Pediatric Dentists On Molar Incisor Hypomineralization, Courtney T. Brashier

Theses and Dissertations

Purpose: The purpose of this cross-sectional, survey-based study is to determine current US pediatric dentists’ knowledge, perceptions, and clinical management strategies for patients with molar incisor hypomineralization (MIH).

Methods: Following appropriate protocol and authorizations, all active pediatric dentists, general dentists, and post-doctoral student members identified by the 2020 American Academy of Pediatric Dentistry’s membership list were invited to partake in an anonymous email survey. Data regarding participants sociodemographic, education, and clinical backgrounds were collected in addition to information obtained from MIH-focused questions. Descriptive statistics and chi-square tests were used to compare and analyze data. A significance level was set at …

Patient Perspectives On Teledentistry And Face-To-Face Doctor Interaction During Orthodontic Treatment, Jackson K. Griffeth D.M.D.

Theses and Dissertations

Purpose: Orthodontic patients were surveyed to determine the perceived value of doctor-to-patient face-to-face interaction, the desire for convenience and attitudes toward specific uses of teledentistry.

Methods: Participating private practice orthodontists emailed the survey to active patients. 75 self-pay patients from VCU Orthodontic clinic were also invited to complete the survey. Patients 18 years or older were asked to complete the survey regarding their own treatment. Parents of patients under age 18 were asked to complete a separate survey regarding their child’s treatment. Questions asked patients about the importance of face-to-face interaction with their orthodontist and their preferences for the inclusion …

Policies Addressing Barriers To Low-Income Women And Children’S Health Care Utilization In The United States And Kenya: The Role Of Physician Payments And Cash Transfer Programs, Muloongo Simuzingili

Theses and Dissertations

This dissertation examined two policies to improve low-income women and children’s healthcare utilization: physician payments and cash transfer programs. Higher physician payments increase the supply of healthcare services while cash transfers increase individuals’ demand for healthcare services. Cash transfer programs can improve health outcomes, yet the extent to which they are a cost-effective strategy is largely understudied. Therefore, this dissertation examines three overarching research questions:

1. Are Medicaid physician fees associated with access to substance abuse disorder (SUD) treatment among low-income women of reproductive age?
2. Do economic preferences moderate cash transfer program effects on children’s health care utilization? Evidence from a …

The Value Of Postoperative Appointments Following Full Mouth Dental Rehabilitation Under General Anesthesia, Priyanka Patel

Theses and Dissertations

Purpose: Follow-up appointments after full mouth dental rehabilitation under general anesthesia (GA) have been suggested as a method for preventing future caries and need for repeat treatment under GA. The purpose of this study is to determine current practitioner and parental perceived value of the postoperative GA appointment.

Methods: Three separate surveys were administered for this study. The pre-appointment survey asked about the guardian’s desire to have a follow-up appointment. At the follow-up appointment, the post-appointment survey ascertained the level of patient satisfaction with their follow-up appointment and postoperative experience. American Academy of Pediatric Dentistry (AAPD) members were e-mailed a …

Radiographic Comparison Using Cbct-Pai And Volumetric Analysis Of Endodontically Treated Teeth: A Retrospective Cohort Study, Jeremy Hargrove

Theses and Dissertations

Purpose: To assess the changes in CBCT-PAI score as well as 3-D volume of periapical findings associated with endodontically treated roots and to see how these findings change over time.

Methods: Retrospective chart review with the following inclusion criteria: 1. At least one tooth was endodontically treated at the endodontic private practice; 2. Patient had a recall examination and the treated tooth was asymptomatic, functional and a CBCT was exposed; 3. CBCT interpretation found a periapical finding associated with the treated tooth; 4. A follow-up recall examination was completed and CBCT exposed. Cases that fulfilled the inclusion criteria had the …

Amixicile, A Novel Antimicrobial Agent, And Its Effect On The Salivary And Subgingival Microbiome In Rhesus Macaque Monkeys, Erin E. Block

Theses and Dissertations

Background/Purpose: Periodontitis is an inflammatory disease with a bacterial etiology in a susceptible host. A selective antibiotic with minimal systemic side effects could be a useful adjunct to traditional periodontal therapy. Amixicile is a novel antimicrobial agent that targets pyruvate: ferredoxin oxidoreductase (PFOR), an enzyme that is critical for anaerobic bacterial metabolism and has been found to have little-to-no side-effects in animal models. The aim of this study was to prospectively evaluate the effect of amixicile on clinical periodontal parameters and the composition of the oral microbiome in rhesus macaque monkeys. It was hypothesized that the amixicile would reduce growth …

A Mixed Methods Approach To Examine Racial Disparities In Adherence To Surveillance Mammography Among Breast Cancer Survivors, Megan C. Edmonds

Theses and Dissertations

PURPOSE: Annual surveillance mammography is a critical part of routine cancer care for breast cancer (BC) survivors; reducing mortality by 39%. However, disparities exist with regard to adherence to surveillance mammograms among BC survivors; Black women are 44% less likely to adhere than their White counterparts. Despite the existence of this racial disparity for over a decade, little is known about factors that explain reasons for Black BC survivors’ non-adherence. This is because most studies have not evaluated the role of healthcare delivery or psychosocial factors. Guided by the Behavioral Model for Vulnerable Populations, the purpose of this mixed methods …

Opioid System's Involvement In Ketamine's Antidepressant-Like Effects, Fan Zhang

Theses and Dissertations

Depression is one of the most debilitating disorders in the world. The currently available medications typically have a 2-4 week delay in their therapeutic effects and are ineffective for about 40% of patients. In 2000, a subanesthetic dose (0.5 mg/kg i.e.) of the dissociative anesthetic ketamine was reported to have both rapid and robust antidepressant effects in in treatment-resistant depressed patients. However, the mechanisms responsible for ketamine’s antidepressant effects remain unclear. In 2018, a clinical study reported that pretreatment with the nonselective opioid antagonist naltrexone attenuated the rapid antidepressant effect of ketamine in depressed patients. The current study investigated the …

A Novel Review Of Heat Shock Protein 110 Kda: A Basis For Research And Continued Experimentation Through Biochemical Analysis, Crist W. Cuffee

Theses and Dissertations

Heat shock protein 110 kDa, Hsp110, is a distinct cellular protector, different in form and function from Hsp70, a close relative of Hsp110. Functioning primarily as a holdase or in tandem with other molecular chaperones, a review of current accomplishments elucidates the uniqueness of this protein and the continued mysteries that surrounds it. Found only in eukaryotes, Hsp110 has been linked to many diseases, ranging from parasitic infection to neurodegenerative disorders. While still lacking, studies of this protein have provided much in the realm of speculation on the mechanisms behind Hsp110s’ contribution to different pathologies. This review will serve as …

Value Of Pediatric Sleep Questionnaire In Referrals For Obstructive Sleep Apnea At Vcu Pediatric Dental Clinic, Elizabeth H. Hering

Theses and Dissertations

Purpose: The purpose of this study is to determine the number of VCU pediatric dental patients screened for obstructive sleep apnea (OSA) relative to the number of referrals made for a pediatric sleep study.

Methods: This was a retrospective chart review of children between the ages of 1-18 years seen at the VCU Pediatric Dental Clinic between 2016-2020. Patients with a completed sleep apnea screening questionnaire in the health history form or sleep apnea form/referral were identified. The data was used to determine how many referrals were made for a pediatric sleep study in patients screening positive for sleep apnea. …

Dendrimer-Based Antibiotics For The Treatment Of Bacterial Biofilm In Cystic Fibrosis (Cf), Younan Ma

Theses and Dissertations

Pseudomonas aeruginosa (PA) is the predominant pathogen in chronic lung infections of cystic fibrosis (CF) patients. The most important mechanism of adaptation of PA to host defense and antibiotic treatment is the formation of biofilms within the mucus layer covering the lung bronchi. The effectiveness of antibiotics such as aminoglycosides is significantly attenuated by their limited penetration through thick mucus and embedded biofilm matrix in patients’ lung. Inhaled tobramycin (Tobra), which is the most commonly used antibiotics in the treatment of PA infections for CF patients, is usually found to be in very high concentration in patients’ lung, and yet …

Formulation, Characterization And Pharmacokinetic Modelling Of Excipient Enhanced Growth Spray-Dried Inhalation Powders, Serena Bonasera

Theses and Dissertations

The overall aim of this research project was to evaluate effects of spray drying parameters and storage conditions on solid-state characteristics and aerosol performance of excipient enhanced growth (EEG) powders and to formulate a stable and highly dispersible tobramycin EEG powder to be delivered to pediatric cystic fibrosis subjects using a novel positive pressure dry powder inhaler.

Micrometer-sized albuterol sulfate EEG powders were produced using a medium-sized nebulizer and optimized spray drying conditions. Using trileucine as the dispersion enhancer improved the aerosol performance but showed increased moisture absorption compared to the L-leucine formulation.

The optimized spray drying conditions were then …

Bisphosohoglycertae Mutase: A Potential Target For Sickle Cell Disease, Anfal S. Aljahdali

Theses and Dissertations

Bisphosphoglycerate mutase (BPGM) is a part of the erythrocyte glycolysis system. Specifically, it is a central enzyme in the Rapoport-Leubering pathway, a side glycolytic pathway involved in the regulation of the concentration of the natural allosteric effector of hemoglobin (Hb), 2,3-bisphosphoglycerate (2,3-BPG). BPGM catalyses the synthesis and hydrolysis of 2,3-BPG through its synthase and phosphatase activities. The synthase activity is the main role of BPGM, while the phosphatase activity is low and is activated by the physiological effector, 2-phosphoglycolate (2-PG) with the latter mechanism poorly understood.

BPGM activity and 2,3-BPG levels in red blood cells (RBCs) have a significant role …

Development Of Sam-Based Chemical Probes For Methyltransferases, Daniel V. Mongeluzi

Theses and Dissertations

Fig.1. SAM analog for the profiling of MTase activity. A. Chemical structure of probe 1; B. General scheme of the labeling and capture strategy.

A

B

Methylation is a fundamental mechanism used in the biological system to modify the structure and function of biomolecules such as proteins, DNA, RNA, and metabolites.¹ Methyl groups are installed by a large and diverse class of S-adenosyl-L-methionine (SAM)-dependent methyltransferases (MTases), which transfer the sulfonium methyl group of SAM to either carbon, nitrogen, oxygen, or other heteroatoms on biomolecules.² Dysregulated MTase activity contributes to numerous diseases, including cancer, metabolic disorders, neurodegenerative diseases. …

Associations Between Social Determinants Of Health And Chlamydia Infections Among Georgia Counties, Bre'auna K. Beasley

Theses and Dissertations

Chlamydia is a growing public health concern that disproportionately impacts southern states. While social determinants of health are not direct causes of chlamydia infections, studies have found that these determinants do influence infections by creating environments that promote or hinder health seeking behaviors, as well as exposure to risk factors. Guided by the Social Ecological Model of Public Health and the Healthy People 2030 Social Determinants of Health Conceptual Framework, this dissertation study aimed to examine the associations between social determinants of health and chlamydia infections among Georgia counties. This study employed a correlational research design. Aggregate-level secondary data for …

Understanding Predictors Of Telemedicine Adoption Before, During, And After The Covid-19 Pandemic, Bradford S. Pierce

Theses and Dissertations

This study examined change in physicians’ use of telemedicine before, during, and expectations after the COVID-19 pandemic. It also examined the ability of personal and environmental variables to predict telemedicine adoption, and applied the theory of reasoned action and technology acceptance model to physicians’ adoption of telemedicine during the pandemic. A total of 230 licensed physicians currently practicing in the United States were recruited. Telemedicine accounted for 3.72% of physicians’ clinical work prior to the pandemic, 46.03% during the pandemic, and predicted 25.44% after the pandemic ends. Physicians within hospitals reported less telemedicine use during the pandemic (M = …

The Strategic Orientation Of Skilled Nursing Facilities, Jennifer R. Palazzolo

Theses and Dissertations

Since the early 2000s, skilled nursing facilities (SNFs) have operated in an environment made uncertain by changes in health care policy, growth in substitutes for nursing care, and increasing demand for services. To better understand how SNFs are strategically positioning themselves to survive and thrive, this study develops a taxonomy of strategic groups of SNFs.

A conceptual framework is based in Strategic Management Theory and classification of SNFs is based on scope of business decisions including length of stay, complexity of patients, and referral networks with hospitals. Two-step, hierarchical cluster analysis finds six strategy groups of SNFs: Post-Acute Care Focus …

Cardiac Arrest And Global Ischemia Reperfusion Injury: Role Of Mitochondria And Cannabinoid Receptor 2 Signaling., Jennifer L. Bradley

Theses and Dissertations

We explored the effects of cardiac arrest on mitochondria populations and heart whole tissue lysate proteomics utilizing the Weil Institute’s in vivo rat model of cardiac arrest and cardiopulmonary resuscitation. We have discovered that brain mitochondria are more sensitive to global ischemia compared to heart mitochondria. Additionally, complex I is the most sensitive electron transport chain complex to ischemic injury and is a major control point of the rate of oxidative phosphorylation following cardiac arrest and cardiopulmonary resuscitation. Preservation of brain mitochondrial activity and function during cardiac arrest may enhance outcomes and recovery.

A recent article focusing on acute myocardial …

Evaluating Patient And Health Care Provider Acceptance Of A Personal Health Record In An Integrated Health Care System In The Kingdom Of Saudi Arabia, Consuela C. Yousef

Theses and Dissertations

With the shift to patient- and person-centered care, personal health records (PHRs) have been touted as a strategy to empower patients, improve patient-provider communication, and support self-management. Health care organizations around the world have implemented PHRs in a global push to meet three aims of health care—improve access to care, reduce costs, and increase the quality of care. The capabilities that PHRs support vary by organizations, yet basic functions include allowing patients to view their laboratory results, refill prescription medications, and request appointments. More advanced PHRs enable patient-centered communication through secure messaging.

As the burden of chronic disease grows, PHRs …

Using The Memorial Sloan Kettering Frailty Index To Identify Patients At High Risk For Postoperative Intensive Care Unit Admission, Specialized Advanced Care Unit Admission, And 30-Day Readmission, Timothy J. Donoghue

Theses and Dissertations

Frailty is roughly defined as an accumulation of physiological, emotional, cognitive, and social deficits that impair a person’s response to stressful events. A frailty diagnosis has been associated with poor outcomes following surgical procedures. Cancer surgical patients aged 65 or older represent a vulnerable population susceptible to being frail and the potential associated complications that can accompany frailty. Measuring frailty is an objective risk assessment that identifies increased risk better than age or American Society of Anesthesiologists Physical Status (ASA-PS) score such that frailty can independently predict poor surgical outcomes.

Frailty is not specifically a result of having cancer, disability, …

Feeling The Squeeze: The Association Between Multigeneration Caregiving And Informal Caregivers’ Health, Christine L. Patterson

Theses and Dissertations

While U.S. public policy and research has focused on the health needs of the aging population, less attention has been given to the consequences informal caregivers face caring for this generation. With the segment of the population aged 65 years or older growing rapidly, it is important to understand the factors that place informal caregivers at risk for poor health outcomes and health behaviors. Since multigeneration caregivers balance more personal, work, and caregiving demands than single-generation informal caregivers of older adults, they may be at higher risk for poor health outcomes. The aim of this study was to examine the …

Strengthening Mental Health Diagnostic Detection In Integrated Primary Care, Julia Brechbiel

Theses and Dissertations

Primary care behavioral health (PCBH) is crucial for providing mental health treatment to underserved, minority, and uninsured populations. There is a lack of knowledge about accurate mental health diagnoses at PCBH. Underdetection of mental health symptoms has the potential to worsen racial and socioeconomic disparities. Using an expert review process, I developed an abbreviated diagnostic clinical interview (ADCI) for integrated primary care. Next, patients (N = 82) completed the interview after attending PCBH appointments. According to the interview, 63.4% of participants met criteria for a diagnosis, while 64.7% received a diagnosis from their provider. A large portion of patients …

Perceived Efficacy Of Extrusion Of Maxillary Lateral Incisors With Aligners, Mason T. Bates

Theses and Dissertations

Purpose: To assess the perceived efficacy of aligners (Invisalign, Align Technology Inc) at performing extrusive movements of maxillary lateral incisors, determine a general threshold of when a maxillary lateral incisor is not extruding as predicted and requiring intervention, evaluate the frequency and methods of intervention to achieve the predicted extrusion, and to evaluate any related differences between orthodontists and general dentists, and between clinicians having treated various numbers of patients with Invisalign in the past 12 months.

Methods: An original 18-question survey was sent by mail to a randomized and geographically proportionate selection of orthodontic specialists (N = …

Validation Of A Screening Tool For Pediatric Obstructive Sleep Apnea: A Pilot Study, Julia A. Giardina

Theses and Dissertations

Purpose: The purpose of this study was to evaluate the Pediatric-Modified-STOP-Bang (PM-STOP-Bang) as a screening tool to assess sleep related breathing disorders (SRBD) within a pediatric population. The specific aims of this study were: 1) compare the PM-STOP-Bang scores with those from the validated Pediatric Sleep Questionnaire (PSQ), 2) determine the ability of the PM-STOP-Bang and the PSQ screening tools to accurately detect children of high risk for SRBD from a one-night home sleep apnea test (HSAT).

Methods: Orthodontic patients were screened using the PM-STOP-Bang at VCU Graduate Clinic. Patients (n=10) who were recruited and enrolled. Five were determined to …

Pushing The Limits: Increasing The Speed And Specificity Of Sars-Cov-2 Testing, Grayson Way

Theses and Dissertations

The prevalence and spread of the current COVID-19 pandemic have highlighted the importance of continual improvements upon current microbiological testing methods. Rapid and accurate testing can help mitigate spread by improving on the time to quarantine and quarantine duration required. As of the writing of this thesis, COVID-19 has been responsible for more than 500,000 deaths in the United States of America, and greater than 2 million deaths globally. The work done in this thesis has shown improvements in the current SARS-CoV-2 testing methodology by reducing the time it takes for patient testing while maintaining accuracy and the sensitivity required …

Modeling Substance Use And Mental Disorder Comorbidity Using Latent Variable And Network Approaches, Courtney T. Blondino

Theses and Dissertations

Introduction. Substance use disorder (SUD) is a common condition that affects millions of Americans. Addressing SUD has been complicated by comorbid mental disorders and co-occurring substance use. Consequently, detailing and addressing SUD and comorbid SUD represent an important goal to improve the health of Americans.

Objective. The research goal of this dissertation was to characterize the comorbidity between substance use, including tobacco use, and mental disorder symptoms measured as negative affect and externalizing symptoms in a population-based sample using latent variable and network approaches.

Methods. Waves 1 – 3 from the Population Assessment of Tobacco and Health Study were used. …

Copper Sulfide Manganese Nanoparticles For Multimodality Imaging And Therapy, Ali S. Gawi Ermi

Theses and Dissertations

Abstract

COPPER SULFIDE MANGANESE NANOPARTICLES FOR MULTIMODALITY IMAGING AND THERAPY

By Ali S. Gawi Ermi, MSc

Inorganic nanoparticles (NPs) are compatible with metal-based multi-modality molecular imaging and targeted therapy. Copper sulfide nanoparticles (CuS NPs) are attractive photoacoustic and photothermal agents and are amenable to incorporation of radionuclides and paramagnetic elements to facilitate image-guided therapy. The aim of this work is to develop manganese (Mn)- doped CuS NP, intrinsically radiolabeled with radionuclides such as (Zirconium-89 (⁸⁹Zr), Copper-64/67 (^64/67Cu) and Manganese-52/55 (^52/55Mn)). This novel approach combines Photoacoustic (PA), Positron emission tomography (PET), Single-photon emission computed tomography …