Exploring Serotonin 1b Autoreceptor Mediated Regulation Of Serotonin Transporter In Female Mice, Sanyukta Jalihalkar

Theses and Dissertations

Rationale: Serotonin (5-HT) is a crucial neurotransmitter involved in regulating various physiological processes. Dysregulation of the serotonergic system has been implicated in several neuropsychiatric disorders. Though numerous 5-HT receptors exist, the 5-HT transporter (SERT) is responsible for 5-HT clearance in the brain and periphery. 5-HT_1Bautoreceptors regulate 5-HT release and interact with glycogen synthase kinase-3β (GSK3β), which can modulate SERT function via specific Ser44/48 phosphorylation sites. While these findings suggest a potential interplay between 5-HT_1Band GSK3β-mediated SERT phosphorylation in regulating extracellular 5-HT, the primary causal molecular link remains unknown.

Objectives: To investigate if 5-HT_1B activation by …

Transforming Children's Oral Health: The Impact Of Oral Healthcare Policies On Virginia Medicaid Dental Health Outcomes., Anita M. Kumar

Theses and Dissertations

Abstract: Transforming Children's Oral Health: The Impact of Oral Healthcare Policies on Virginia Medicaid Dental Health Outcomes.

Objectives: This dissertation uses Department of Medical Assistance Services (DMAS) administrative files at the individual and provider level from fiscal years (FY) 2011 to 2021 to systematically study the effect of recently implemented oral health policies (EBD guidelines on sealants, CMS updated quality measures, expansion of Medicaid oral healthcare for qualifying pregnant women) on oral health outcomes of Virginia Medicaid-enrolled children.

Methods: The studies employ a difference in differences regression methods (negative binomial, Poisson, and logistic) to examine the effects of oral health …

Exploration Of Dopaminergic And Serotonergic Pathways Utilizing Pleiotropic Agents, Charles B. Jones Iii

Theses and Dissertations

2-(Benzoyl)piperidines (BPs) are at a crossroads of therapy and abuse. These compounds are a hybrid between the ADHD medication methylphenidate and abused stimulant cathinones. Here we use computational molecular modeling, synthesis, mutagenesis, and epifluorescence microscopy to further improve the understanding of and potential treatments for several neuropsychiatric disorders. Utilizing the BP scaffold and controlling chirality and aryl substitution, these agents were examined at DAT and SERT. From these investigations it has now been established that R isomer BPs are favored for DAT while S isomer BPs are favored for SERT. Aryl-substitution can greatly affect the selectivity of these agents with …

Muscle-Nerve Signaling And Its Role In Myogenesis, Synaptogenesis, And Regeneration, James T. Redden

Theses and Dissertations

Despite only comprising 0.1% of the myofiber surface area, a healthy motor endplate is densely packed with acetylcholine receptors (AChRs) responsible for mediating activity between the connected motor neuron and skeletal muscle via the neurotransmitter, acetylcholine. Loss of the endplate, known as fragmentation, is caused by car crashes, deep lacerations, and other traumatic injuries to the innervating nerve or direct injuries to the limb muscle(s) with intramuscular denervation as a common comorbidity. In both cases, endplate fragmentation begins within a week of injury proceeding muscle atrophy causing decreased mobility, paralysis, and quality of life. Endplate fragmentation of intact muscle fibers …

The Many Impacts Of The Covid-19 Pandemic On Latinx College Students’ Mental Health: Exploring The Role Of Sleep, Social Support, And Familismo, Mayra S. Ramos

Theses and Dissertations

College students experienced a multitude of disruptions to their daily life, and changes to their physical (i.e., sleep quality) and mental health (e.g., anxiety and depressive symptoms) because of the COVID-19 pandemic. Though the field has identified the factors that have contributed to negative physical and mental health changes, there remains much to be known about social and cultural protective factors that could buffer the negative role of the COVID-19 pandemic on Latinx college students. The current study contributed to the literature on the mental health outcomes of Latinx college students by identifying a possible mediator and moderators between the …

Mild Traumatic Brain Injury In Yucatan Minipigs: Assessing Changes In Approachability And Mechanical Nociception Following Diffuse Central Fluid Percussion Injury, Mark D. Pavlichenko

Theses and Dissertations

Traumatic brain injury (TBI) is a major healthcare concern affecting millions. Symptoms of TBI include sensory sensitivity and social changes that may persist long-term. Due to similarities in cytoarchitecture, metabolism, and inflammation, higher order minipig models are advantageous for translational TBI research, however, there remains a shortage of information regarding their behavioral and sensory sequelae following injury. Therefore, in this study, we assessed changes in sociability and somatosensation in adult male and female Yucatan minipigs for up to one-week following a sham or central fluid percussion injury (cFPI). Specifically, the voluntary human approach task (VHAT) and the forced human approach …

Neurodevelopmental Trajectories As An Explanatory Mechanism For Adverse Mental Health Outcomes Following Child Maltreatment, Casey Burton Corso

Theses and Dissertations

Affecting one in every seven children in the United States, child maltreatment (CM) is a major public health issue associated with a myriad of adverse outcomes (e.g., alcohol and drug abuse, mental illness, interpersonal violence, sexual risk taking, etc.). While any subtype of CM (e.g., physical abuse, sexual abuse, emotional abuse, and neglect) increases the likelihood of subsequent psychopathology, heterogeneity in psychiatric sequelae of CM is associated with different CM subtypes. Elucidating the underlying mechanisms of this heterogeneity is vital for improving intervention and treatment of CM, and research aimed at accomplishing this is a critical need. One possible explanatory …

Potential Treatments For Epileptiform Activity In Microgyral Cortex, Eliot R. Niessen

Theses and Dissertations

In this study, the effects of several drug treatments on epileptiform activity in the freeze lesion (FL) mouse model of epilepsy have been evaluated and compared. The FL model replicates the histopathology and epileptiform activity that occurs in humans with the developmental cortical malformation of polymicrogyria (PMG). While Gabapentin is already used in a clinical setting to treat seizures, there are other alternatives that have not been fully tested. Rapamycin, for instance, has been shown to reduce seizures in other models of epilepsy. It is an inhibitor of the mammalian target of rapamycin (mTOR) pathway, which regulates the function of …

Mathematical Modeling Of Phage-Bacteria Population Dynamics, John Lawrence D. Palacios

Theses and Dissertations

Bacteriophages are viruses that infect and replicate within bacteria. Lytic phages cause the bacterial cell to burst, killing the bacteria. These types of phages can be used to treat patients with antibiotic-resistant bacterial infections. As a step in developing successful treatment protocols, we aim to understand the population dynamics of phages and bacteria using an in vitro model. We model the dynamics using the Campbell model, which consists of a delay differential equation (DDE), as a base model. We extended the model by including the emergence of phage resistance. We then compared the DDE model with a parallel ordinary differential …

T Cell Polarization Regulates The Inflammatory Response And Tissue Regeneration At The Peri-Implant Interface, Derek Avery

Theses and Dissertations

Unresolved healing and localized chronic inflammation are common occurrences after biomaterial implantation, resulting in unfavorable clinical outcomes such as implant failure or fibrous encapsulation. T cells are adaptive immune cells found in lymph nodes, thymus, spleen, bone marrow, and around biomaterials, significantly impacting the degree of inflammation and wound healing. T cells are vital for inflammatory cytokine production and modulation of innate immune cells, including neutrophils and macrophages. T cells can be differentiated into two primary subsets, CD4⁺ and CD8⁺ T cells, playing distinctive roles in various pathologies and disease states. While T cells have been characterized well …

Using Asset-Based Community Development To Increase Student Engagement And Improve Student Experience In Schools, Jacqueline Hopkins

Theses and Dissertations

The following is a dissertation in the three-paper dissertation format. The first section will give background information on the issue of alienation in schools and how asset-based community development (ABCD) could be an effective tool for educators to combat alienation and disengagement, especially with students with marginalized identities. This first section will also show the significance of the three papers as a whole and how they connect to one another. The first paper is the conceptual literature review, the second paper is an empirical study of the ABCD model in schools, and the dissertation will end with a practitioner's article …

How Ebony Transcends In The Ivory Tower: Unveiling Transformational Black Women Forging Leadership Paths In Historically White Institutions, Lauren N. Jackson

Theses and Dissertations

Considerable literature has amplified the perceived challenges and deficits of Black women as they advance in their careers within historically white institutions (HWI). As a result, there is a notable absence of anti-deficit explorations of the inherent abilities and strengths that contribute to Black women’s professional mobility. Grounded in anti-deficit achievement framework and Black feminist leadership, this study aimed to illuminate the assets and factors that influence the professional ascension of seven, current/former senior-level Black women in a HWI within the Southeastern region of the U.S. By adopting a qualitative, phenomenological framework, this study provides in-depth insights into the participants’ …

Genetic And Transcriptomic Investigations Of Progressive Ethanol Consumption In The Diversity Outbred Mouse, Zachary Tatom

Theses and Dissertations

As a complex genetic disorder, alcohol use disorder (AUD) is thought to be influenced by many genes each contributing only a small effect to the overall disease liability. Dozens of genes have been implicated as potentially affecting risk for AUD and alcohol consumption. However, understanding the full genetic architecture of AUD – what genes are involved, to what extent, and how these genes are regulated – remains a challenging step in identifying novel treatments. Gene expression studies in humans have attempted to augment GWAS of alcohol consumption but are often confounded by environmental factors; the difficulty of collecting tissue from …

Longitudinal Analysis Of Maternal Depression, Physical Work Demand, And Working Hours Before, During, And After Pregnancy On Offspring Blood Pressure Trajectories, Medhin Tsegaye Haile

Theses and Dissertations

Overall Abstract

Background: Pediatric high blood pressure (BP) is a growing global concern, with 1 in 7 adolescents in the U.S. experiencing elevated BP or hypertension. Maternal lifestyle factors, including depressive symptoms, physically demanding work, and work hours during pregnancy, may influence offspring BP trajectories. However, prior studies often focus on single time points or specific age groups, limiting understanding of long-term effects. This study investigates the associations between maternal depressive symptoms, physically demanding work-related factors, and work hours before, during, and after pregnancy with offspring systolic blood pressure (SBP) trajectories from early childhood to adolescence.

Methods: We utilized …

Cellular Metabolism Is A Viable Therapeutic Target For Radiation-Induced Pulmonary Fibrosis, Josly Pierre-Louis Odoom

Theses and Dissertations

Herein, we provide evidence for cellular metabolic reprogramming as a driver of radiation-induced pulmonary fibrosis (RIPF). We are the first to identify a distinct metabolic signature for RIPF in a cohort of patients with radiographic sequela. We also used a RIPF mouse model to detect the metabolic pathways that enrich during pathogenesis. Our previous work highlighted the importance of lactate, a derivative of the glycolysis end-product pyruvate. Consequently, we took a special interest in the effects of radiation on the glycolysis pathway. We learned that radiation accelerates and reprograms glycolysis to an anabolic state in a pyruvate kinase M2 (PKM2)-dependent …

Examining Parent Behavior And Adolescent Outcomes In A Pediatric Obesity Intervention, Madison W. Weinstock

Theses and Dissertations

Pediatric obesity is a major public health concern that affects over 14.4 million children and adolescents in the United States. Multiple short- and long-term health complications are associated with obesity. Therefore, effective treatment methods are needed in order to ameliorate the effects of said complications, particularly among adolescents. This dissertation investigated potential associations between parent eating behaviors and the outcomes of adolescents enrolled in a pediatric weight loss trial (TEENS+; PI: Bean, R21HD084930). The TEENS+ intervention offered a comprehensive behavioral weight intervention for parent-adolescent dyads. Given the well-established importance of parents in the development of an adolescent’s health behavior, this …

Life After Discharge: Predicting Longitudinal Trajectories Of Community Integration And Global Functioning In Black Individual With Traumatic Brain Injury, Chimdindu Ohayagha

Theses and Dissertations

The onset of traumatic brain injury (TBI) begins a chronic health pathway that contributes to various impairments and comorbidities across the lifespan. Common consequences of TBI include mental health issues, cognitive impairments, and reduced functional independence, all of which impact how an individual integrates into their community. Community integration is a primary goal for rehabilitation after TBI. Studies show that racially/ethnically minoritized individuals have a higher incidence of TBI, higher rates of mortality, and report poorer functional and community integration outcomes. Limited studies have explored longitudinal outcomes of community integration in a Black-only sample of individuals with TBI. Additionally, no …

Functional Monitoring For Run-Time Assurance Of A Real-Time Cyber Physical System, Matthew W. Gelber

Theses and Dissertations

As cyber-physical systems (CPS) become more integrated into everyday life, the security of these systems must also be considered during their development due to their ever-increasing importance. With the growth of physical components in the system, more autonomous control requirements, and increased dependence on proper functionality, verifying system safety and correct operation becomes increasingly difficult. CPS have become more complex through the combination of additional hardware and the resulting interconnected software in many layers, each requiring unique security solutions. One example of such a safety-critical CPS embedded system is the Flight Control System (FCS) of an Unmanned Aerial System (UAS). …

Essays On The Impacts Of Macra 2015 And Market Dynamics On Quality, Billing, And Fraud In The U.S. Healthcare System, Mahmoud Manouchehri Amoli

Theses and Dissertations

This thesis presents a comprehensive examination of the impacts of the Medicare Access and CHIP Reauthorization Act of 2015 (MACRA) and market dynamics on the quality, billing practices, and incidence of fraud within the U.S. healthcare system. It is a compilation of three essays that each delves into a specific facet of the healthcare landscape altered by MACRA's introduction and the evolving market conditions.

Chapter 2 analyzes how MACRA has transformed Medicare Part B physicians' practices by introducing the Merit-Based Incentive Payment System (MIPS) and Advanced Alternative Payment Models (APMs). The study provides empirical evidence on the shift in billing …

Utilizing Hemoglobin Binding Kinetics And X-Ray Crystallography In Sickle Cell Disease Drug Development, Ahmed Alghamdi

Theses and Dissertations

ABSTRACT

UTILIZING HEMOGLOBIN BINDING KINETICS AND X-RAY CRYSTALLOGRAPHY IN SICKLE CELL DISEASE DRUG DEVELOPMENT

By Ahmed Alghamdi, M.Sc. in Medicinal Chemistry

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

Virginia Commonwealth University, 2024.

Director: Dr. Martin K. Safo Professor, Department of Medicinal Chemistry

Introduction: Sickle Cell Disease (SCD) is characterized by severe hemolytic anemia, recurrent painful crises, and chronic organ damage, posing significant challenges to patients' quality of life and longevity. While current FDA-approved therapies offer symptomatic relief, they do not address the underlying molecular …

The Patient Experience Of Language Discordance And Interpreter Services In The Emergency Department, Keri L. Baker

Theses and Dissertations

Background: Clear communication is critical to the interaction of a patient and medical provider. For non-English speaking patients, language discordance, described as the lack of proficiency in a shared language, with the medical team results in a poor patient experience and poor patient outcomes. The predominant solution to language discordance is the use of interpreter services, however these services are underused in the emergency department (ED). Studies examining underuse of interpreter services have primarily focused on the clinician and little is known about the patient’s influence on the use of interpreter services.

Methods: Semi-structured interviews were conducted with 12 Spanish-speaking …

Continuous Flow As A Process Intensification Tool For The Preparation Of Pharmaceutically Relevant N-Heterocycles, John W. Tomlin Jr

Theses and Dissertations

Continuous flow as a process intensification tool for the preparation of pharmaceutically relevant N-heterocycles

John W. Tomlin

Thesis Defense: 17 January 2024

Committee: B. Frank Gupton, Ph.D. (Advisor), Suzanne M. Ruder, Ph.D. (Chair), Heather R. Lucas, Ph.D., James K. Ferri, Ph.D., Matthew C.T. Hartman, Ph.D.

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

© 2024 John W. Tomlin Jr All Rights Reserved

Abstract

Essential medicines must be produced in large quantities to accommodate large global demand. The preparation of these active pharmaceutical ingredients (API) must therefore strive to be both cost-effective …

Mechanistic Analysis Of Four-Way Dna Junctions And Cytokine-Binding Aptamers For Therapeutic Interventions, Roaa S. Mahmoud

Theses and Dissertations

DNA is inherently dynamic and topologically diverse and can fold into many different structures. Besides the canonical Watson-Crick structure, other higher-order structures such as G-quadruplexes (G4), i-motifs (iM), and four-way DNA junctions are possible. Although these high-order DNA structures are known to form transiently, they are important due to the crucial roles they play in many cellular processes including DNA replication, recombination, and repair. Among these DNA structures, 4-way junctions (also known as Holliday junctions, HJ) which are formed during the repair of double-strand DNA breaks (DSBs) and interact with proteins have garnered significant attention due to their central role …

Polyvictimization In Context: Identifying Patterns Of Peer, Dating, And Community Violence Among Black Early Adolescents, Carine Leslie

Theses and Dissertations

Early adolescents exposed to multiple forms of victimization (“polyvictimization”) may experience a number of detrimental psychosocial outcomes. Some person-centered research has identified victimization subgroups among adolescents but have not examined the overlap of peer, dating, and community victimization among Black early adolescents living in economically disadvantaged urban communities. Thus, this study empirically identifies victimization profiles in a sample of Black early adolescents to ascertain the patterns and correlates of polyvictimization. The present study aimed to (a) identify subgroups of Black early adolescents based on their frequency of peer, dating, and community victimization using latent profile analyses, and (b) evaluate the …

Repeated-Measures Latent Profile Analyses Of Intervention Fidelity To A Teacher-Delivered Intervention Program For Children At Elevated Risk For Emotional And Behavioral Disorders, Katrina A. Markowicz

Theses and Dissertations

Teachers have difficulty delivering Tier-2 intervention programs for preschoolers at elevated risk for socioemotional and behavioral disorders with high intervention fidelity (Durlak, 2010; Sutherland et al., 2018). Several proximal factors that impact program fidelity have been identified, which may undermine program effects (Domitrovich et al., 2008; McLeod et al., 2022; Sutherland et al., 2018). Therefore, researchers have identified strategies, such as practice-based coaching, to improve intervention fidelity and support teachers (Hemmeter et al., 2015; Synder et al., 2015). Most of the field's knowledge of these topics is limited to variable-centered approaches (Fettig et al., 2022; Low et al., 2016). However, …

Correlates Of Coffee And Energy Drink Use Among Individuals With Severe Alcohol Use Disorder, Enkelejda Ngjelina

Theses and Dissertations

Research on caffeine consumption among college students and young adults has primarily focused on caffeinated energy drinks (EDs) and their combination with alcohol, demonstrating a strong association with heavy and problematic alcohol use. However, little attention has been directed toward older adults. Furthermore, studies have shown that regular ED consumers are more likely to meet the criteria for alcohol dependence compared to their peers. Despite this association, little is known about ED consumption among individuals with Alcohol Use Disorder (AUD), particularly those undergoing treatment, and even less is understood about other caffeine sources such as coffee. This study aimed to …

Systemic Contributors To Health Equity: A Conceptual Framework And Moderation Analysis, Rachel Regal

Theses and Dissertations

This dissertation presents a line of research exploring systemic factors that influence health and health equity across the lifespan. A linking document prefaces two-manuscripts as follows. Manuscript 1, A Model for Enhanced Trauma-Informed Care: An Asset-Based, Transdisciplinary Approach to Health Equity, presents a synthesis of literature on multisystem resilience, social determinants of health, and adverse / positive childhood experiences to build an alternative framework to promote healing and health equity using an asset-based approach within enhanced trauma-informed systems of care and educational models. By adopting this enhanced framework, the counseling field and others can be responsive to emerging trends and …

The Genetic Architecture Of Cervical Change During Pregnancy: From Modeling To Mechanism — Does The Cervix Mediate Maternal Risk For Spontaneous Preterm Birth?, Hope M. Wolf

Theses and Dissertations

This project leverages clinical data and biospecimens from a prospective longitudinal cohort of pregnant women to study the genetic and phenotypic relationships between cervical shortening and the duration of pregnancy. Sonographic cervical length (CL) was measured throughout pregnancy in a cohort of 5,160 Black/African American women in Detroit, Michigan. Maternal DNA samples were sequenced with a next-generation low-pass whole genome platform. The heritability of cervical change during pregnancy and its genetic correlation with gestational age at delivery (GAD) were estimated using Genome-Wide Complex Trait Analysis. These estimates suggest that cervical change is heritable (h²CL = 51%) and highly polygenic trait. …

Feasibility Of Using Somatosensory Input On Pediatric Patients Receiving Dental Treatment, Liara D. Vinson

Theses and Dissertations

Purpose: The aim of this randomized, cross-over designed feasibility study is to evaluate patient anxiety, patient cooperation, and patient acceptance of a vibrating weighted vest used during the restorative treatment compared to when no device is used.

Methods: Children aged 5 to 15 years, needing at least two appointments for restorative treatment requiring local anesthesia under basic behavior guidance techniques were recruited. Patients were randomly allocated to wearing a vibrating weighted vest at one of the appointments. At both appointments, behavior was evaluated using Frankl scores and anxiety was evaluated at the beginning and at the end of …

Towards The Automation Of Post-Processing Of Additive Manufacturing Using Collaborative Robots, Logan Schorr

Theses and Dissertations

Despite the incredible potential that collaborative robots have, they are underutilized in several industries that could benefit greatly. These specialized fields, such as additive manufacturing, face challenges that can be solved with the use of robotics, including advanced computer vision, end-effector tooling, and process refinement. My research aims to utilize collaborative robots in an effort to solve the above stated problems, for the specific fields of additive manufacturing. Specifically within this field is the automation of post-processing; this is normally completely manual, as the tools for automation are not sufficiently developed to handle the flexibility required for additive manufacturing. This …