Established Colonization Of Sneathia Vaginalis In A Mouse Model, Kailyn E. Turcios-Gonzalez

Theses and Dissertations

Sneathia vaginalis (Sv) is a gram-negative anaerobic bacterium associated with adverse reproductive outcomes. Sv can traverse the fetal membrane and damage epithelial cells in vitro by producing a pore-forming cytotoxin, cytopathogenic toxin A (CptA). To further understand the transition of Sv from normal flora to a pathogen, an animal in vivo model needs to be created to observe the preliminary ascending infection before we begin to study the effects on pregnancy. Experimentation was conducted to optimize mouse breed, bacteria administration methods, and other variables that arise when working in vivo. The C57BL/6 mouse strain displayed the most consistent …

Capiz Reborn: Preserving And Enhancing Traditional Philippine Shellcraft, Destarte A. Prieto

Theses and Dissertations

The capiz shell is a thin, translucent exoskeleton of a mollusk found in the Philippine Sea. Traditionally, capiz shells were made into window panes and home decor, used so widely they became an iconic part of Philippine identity. Today, the influx of cheap, mass-produced merchandise threatens the capiz shell industry. To encourage renewed interest and sustainable revival of this long-standing industry, my research demonstrates new possibilities for the capiz shell.

In reconstituting cast-off bits and shell trimmings to form a new capiz biomaterial, my work is informed by the three traditional techniques used by Philippine capiz artisans—sewing, welding and bonding. …

Acute Effects Of An Oral Nicotine Pouch In People Who Use Smokeless Tobacco, Alisha Eversole

Theses and Dissertations

People who use smokeless tobacco (SLT) are exposed to a variety of carcinogenic toxicants, yet, despite health risks, nearly 6 million people in the US use SLT. SLT contains and delivers nicotine, a psychostimulant that causes dependence and hinders cessation efforts. An orally-administered nicotine pouch marketed as “tobacco-free” recently has become available for purchase in the US. However, there are very few non-industry-sponsored studies regarding the effects of these oral nicotine pouches.

The current study used clinical laboratory methods to determine the acute effects of an oral nicotine pouch in people who use SLT. Participants completed four sessions (within subjects, …

Assessing Providers’ Readiness To Integrate Mat Services In A Primary Care Setting, Carmen Ingram-Thorpe

Theses and Dissertations

Opioid use disorder is a growing concern in the United States. Despite medication-assisted treatment (MAT) being a more effective treatment option than behavioral treatment alone, primary care providers’ rate of adoption and utilization of MAT has not matched the demand of the opioid crisis. The largest barrier facing our local community is the availability of organizations and providers that can and will actually provide MAT services. The purpose of this study was to identify factors that impact primary care providers’ readiness to treat individuals with opioid use disorder (OUD) using MAT. This study used the ADKAR model as framework, which …

Investigating The Impact Of Chronic Inflammatory Pain On Ethanol Consumption In Mouse Models., Joshua L. Hunt

Theses and Dissertations

Chronic pain affects nearly 20% of Americans annually and for many alcohol provides a convenient and legally acquired palliative. Population-based studies have suggested a link between increased alcohol use and reduced pain, but chronic or excessive alcohol use potentiates the risk to develop alcohol dependence and neuropathy. However, sex differences in chronic pain and alcohol abuse are still not well understood. In the present study, we investigated whether chronic inflammatory pain using the inflammatory agent Complete Freund’s Adjuvant (CFA) model could alter ethanol consumption in male and female C57BL/6J mice. We observed that only CFA-treated male mice increased their ethanol …

Problems In Graph Theory With Applications To Topology And Modeling Rna, Rayan K. Ibrahim

Theses and Dissertations

In this thesis, we explore four projects. In the first project, we explore $r$-neighbor bootstrap percolation on a graph $G$. We establish upper bounds for the number of vertices required to percolate in the case that $r=2$ for particular classes of graphs. In the second project, we study the structure of graphs with independence number two. We prove a lower bound on the number of edges of such graphs, related to an upper bound on the number of edges in a triangle-saturated graph, and give a sufficient forbidden induced subgraph condition for independence number two graphs. In the third project, …

Memory Impairments Due To Binge Ethanol Are Impacted By Age And Sex, Maria Alexis M. Bent

Theses and Dissertations

Ethanol is the most consumed drug among adolescents, which can cause long-term effects on memory and changes in gene and protein expression. While both adolescents and adults engage in binge drinking, the neurological and behavioral effects differ, with adolescents showing fewer adverse physiological effects but greater memory deficits than adults. Sex differences related to ethanol occur with women showing higher BEC than men and similar cognitive deficits despite fewer years of ethanol consumption. During adolescence the mPFC and dHPC undergo maturation development with both brain regions playing a role in spatial and recognition memory. Proteins critically involved in memory and …

Exploring The Role Of Senescence In Disuse-Induced Bone Loss And Therapeutic Strategies For Prevention, Steven J. Meas

Theses and Dissertations

Both age-related and disuse-related bone loss result in decreases in bone mineral density, cortical thickness, and trabecular thickness and connectivity. Disuse induces physiological changes in bone similar to those seen with aging. This study compared age- and disuse-related bone loss using C57BL/6J mice of various ages that were hind-limb unloaded (HLU). In male and female mice, HLU induced a bone phenotype between those of 6-month-old and 22-month-old control mice. Gene analysis suggested that HLU leads to mitochondrial dysfunction, while aging primarily downregulates cell cycle processes. Although, the specific response to HLU appeared to be dependent on age. The study identified …

Leaf To Canopy Functional Resilience: Plant Physiological And Carbon Cycling Stability Following Disturbances, Lisa T. Haber

Theses and Dissertations

Ecological disturbances impact core ecosystem functions, including production and biogeochemical cycling, by precipitating changes in biodiversity, physical environmental variables, vegetation structure, and functional trait distributions. As disturbance patterns intensify and abruptly transition to novel regimes under global change, future trajectories of ecosystem functions, including carbon (C) uptake and storage, are uncertain. A more complete understanding of the mechanisms underpinning ecosystem stability (or ability to return to baseline functioning) following disturbance is needed to forecast future C cycling.

Replicated ecosystem-scale disturbance experiments, particularly when coupled with modeling, are required to rigorously test hypothesized trajectories of ecosystem structural and functional change following …

The Relationship Between Outcomes Associated With Patient Blood Management Programs And Transfusion Safety Officers, Gary Morral

Theses and Dissertations

BACKGROUND: Patient Blood Management (PBM) has become the standard of care for transfusion services in hospitals. Transfusion Safety Officers (TSOs) have been identified by some as being a crucial part of a successful PBM program; however, no studies have been done to show their effectiveness, or if there is even a relationship between having a TSO and outcomes associated with PBM programs. The purpose of this study was to describe and test the relationship between having a TSO and six outcomes associated with PBM programs including blood product wastage (red blood cells, plasma, and platelets), hospital lengths of stay, rates …

Enhancing Chemotherapeutic Efficacy Of Doxorubicin Through Combination Therapy With Rapamycin And Sildenafil, While Providing Cardioprotection In Breast Cancer Models, Rebecca Mathew

Theses and Dissertations

Doxorubicin (DOX) is a common chemo-drug for breast cancer, but it causes severe cardiotoxicity. This study explores combining Sildenafil (Sild) and Rapamycin (Rapa), which inhibit phosphodiesterase-5 (PDE5) and mTOR, respectively, to boost DOX’s anticancer, but provide cardioprotection. Triple negative human (MDA-MB-231) and murine (4T1) breast cancer cells were treated with DOX (1 µM) with/without Rapa (100 nM) and Sild (10 µM) for 24-72 hours to analyze cell death, cell viability assays and protein expression. Human epidermal growth factor receptor 2-positive breast cancer (SKBr3) spheroids were treated with the same concentrations of DOX and/or AG825 (5µM) with/without Rapa and/or Sild for …

Mathematical Analysis Of Eukaryotic Pericentromere, Puranjan Ghimire

Theses and Dissertations

The centromere is crucial for chromosomal stability and their proper segregation during cell division in eukaryotes. Surrounding the centromere are pericentromeres, made of repetitive DNA elements called pericentromeric repeats, varying from 10 in fission yeast to thousands in humans. These repeats form densely packed heterochromatin, where genes are usually silenced. The silencing mechanism across different pericentromeric repeats remains unclear.

Despite variations in sequence and length, pericentromeric repeats are conserved across eukaryotes, indicating their functional importance. This dissertation presents mathematical models to quantify gene silencing in fission yeast and humans. In fission yeast, my model predicts that silencing occurs only with …

The Regulation Of Laryngeal Cancer Cell Phenotype And Proliferation By 24r,25-Dihydroxyvitamin D3 Is Correlated With Erα Isoform Expression, Cydney Dennis

Theses and Dissertations

Laryngeal cancer is the most common type of head and neck cancer and is associated with poor prognosis due to common delayed diagnoses. The sex disparities associated with laryngeal cancer are constantly growing, as the risk of malignancy in males is continually increasing compared to women. Due to the high chance of late-stage diagnosis requiring aggressive treatments, there is a high demand for less aggressive treatment options and early-stage diagnostic markers. The apparent sex disposition of the larynx, the correlation between sex hormones, and the risk of malignancy in aging men suggest that estrogen may play a role in laryngeal …

Behavioral Effects Of Adolescent Social Isolation Stress And/Or Binge Drinking And The Role Of The Vhip --> Mpfc Circuit, Jyoti Lodha

Theses and Dissertations

Adolescence is characterized by heightened social interaction and risk-taking behavior. Disruptions to cortical development by binge ethanol or social isolation can lead to attention, social, and cognitive deficits later in life, and increase risk for alcohol use disorders. During adolescence, proper development of a monosynaptic connection from the ventral hippocampus (vHip) to the medial prefrontal cortex (mPFC) is critical to proper social and working memory. We ask whether these factors affect neurobiological factors such as gene expression and the role of the vHipmPFC circuit in these behaviors. Social stress was modeled by social isolation (aSI) during adolescence. We expect aSI …

A Complexity Aware Overlay Architecture For High Integrity Fpga Based Systems, Richard Dwight Hite Jr

Theses and Dissertations

Cyber-Physical systems are becoming more and more prevalent in our society and are simultaneously becoming more complex due to evolving technological capabilities in both hardware and software. This complexity exacerbates verification and validation activities thereby negatively impacting important system attributes like design assurance, system reliability, development costs and trust. These facts necessitate the need for computing architectures that constrain complexity for the sake of assurance. Traditional software and hardware development for safety-critical systems have been demonstrated in previous safety-critical systems and the established development methodologies are well understood. However, both technologies have their strengths and limitations. Processor-based technology (SW based …

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 …

Effects Of Flooding And Plant Community Arrangement On Freshwater Wetland Greenhouse Gas Emissions And Plant Growth, Walker A. Trainum

Theses and Dissertations

Climate change threatens the status quo of tidal freshwater wetlands by altering their hydrology and species makeup. Increases in water level within freshwater wetlands are well studied, but with the inclusion of saltwater intrusion; while common for some tidal wetlands affected by sea level rise, it is not universal. For wetlands that will experience flooding apart from increases in salinity, adequate study is lacking. For these wetlands, the effect of increasing water level is largely unknown. Thus, the aim of this study was to use an outdoor mesocosm experiment to isolate effects of flooding and communities of differing species makeups …

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 …

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 …

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 …

Multi-Magnetic Material Transcranial Magnetic Stimulation Coils Development And Electric Field Measurement & Modeling Using Machine Learning, Mohannad Tashli

Theses and Dissertations

Transcranial Magnetic Stimulation (TMS) is a safe, effective, and non-invasive therapy for treating several psychiatric and neurological disorders. TMS is Food and Drug Administration (FDA) approved treatment and is commonly applied to patients who do not respond to medications for the treatment of clinical depression, smoking cessation, obsessive-compulsive disorder and migraine. Recently, there has been an increase in the development of electromagnetic neuromodulation techniques targeted at enhancing the effectiveness of TMS devices for the treatment of mental diseases. In TMS stimulation, focality is an important factor which determines the specificity of the pulses induced in different brain tissues. The electromagnetic …

Evaluation Of Alternative Methods For Dna Recovery Of Compromised Skeletal Remains, Ciara N. Rhodes

Theses and Dissertations

Skeletal remains frequently serve as the sole source of genetic material available for developing a profile in cases concerning unidentified human remains or mass casualties. Nevertheless, as unidentified skeletal remains age and are exposed to uncontrolled environmental conditions, the success rates of conventional methods of bone analysis diminish significantly. The physical and mechanical processing of skeletal remains into fine powder for DNA isolation and downstream analysis can substantially impact the quality and quantity of recoverable genetic information. This concern may be exacerbated when dealing with degraded forensic skeletal remains. Few studies have explored whether pulverization of bone samples contributes to …

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 …

Long-Wave Modeling Of Viscous Film Dynamics Inside A Tube With Time-Dependent Radius, Robert E. Hicks

Theses and Dissertations

Lung fluid dynamics is a well studied topic and relevant in the field of research surrounding patients with Chronic Obstructive Pulmonary Disease (COPD) and cystic fibrosis. However, the literature on the mathematical description of the net pulmonary fluid transport in the case of constricting and expanding airways is scarce. In this paper we aim to address how breathing contributes to airways clearance in patients with pulmonary diseases such as COPD and CF in which cilia do not function properly. We begin with the flow of a fluid-filled tube with rigid walls of fixed radius and the effects of gravity being …

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 …

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 …