Digital Commons Network^™

Investigating Cannabinoid Type-1 Receptor (Cb1r) Positive Allosteric Modulators (Pams) In Mouse Models Of Overt Cannabimimetic Activity, Subjective Drug Effects, And Neuropathic Pain, Jayden Elmer

Theses and Dissertations

Chronic pain affects between 20 and 30 percent of the adult population in western countries and represents a wide array of specific etiologies (Berge, 2011). Neuropathic pain secondary to traumatic nerve injury, chemotherapeutic toxicity, or diseases (e.g., diabetes mellitus) is often refractory to conventional analgesics, with patients receiving less than 50% pain relief compared to placebo (Finnerup et al. 2010). The endocannabinoid system has shown potential as a therapeutic target for neuropathic pain wherein CB1 agonism via administration of exogenous agonists or pharmacological blockade of endocannabinoid catabolic enzymes exhibits efficacy in reversing allodynia in the chronic constriction injury (CCI) model …

Pharmacophoric Evaluation Of 5-Ht2a And 5-Ht2b Serotonin Recpeptors, Prithvi Hemanth

Theses and Dissertations

Serotonin (5-HT) receptors represent a class of receptors involved in a variety of physiological processes including regulation of mood, perception, cognition, appetite, and heart function, and thus serve as drug targets of several drugs such as antipsychotic agents, hallucinogenic drugs, and appetite suppressant drugs. Due to the structural similarity of certain 5-HT receptor subtypes, particularly 5-HT₂ receptors (5-HT_2A, 5-HT_2B receptors) determination and refinement of pharmacophore models of these receptor subtypes can greatly improve the therapeutic efficacy of drugs that target them.

The goals of this study were to define and/or refine existing pharmacophore models for 5-HT …

Intentions To Use Telerehabilitation For Communication And Treatment For Vision Impairments, Eric E. Hicks

Theses and Dissertations

BACKGROUND: Approximately 8.1 million people in the United States 18 and older have difficulty performing one or more daily activities because of vision impairment or blindness (Erickson, Lee, & von Schrader, 2020; Taylor, 2018). If the impairments caused by vision loss are not addressed, they can result in financial difficulties, suffering, disability, loss of productivity, and decreased quality of life (National Center for Chronic Disease Prevention and Health Promotion, 2011). Currently, in-person low vision rehabilitation services are the gold standard for teaching people how to adapt to and compensate for these deficits, however, the access and utilization of these services …

Impact Of Targeting Glycosylated Ceramides On Tumorigenic Properties, And Characterization Of Sphingolipids In Head And Neck Tumors, Katherine E. Hylton

Theses and Dissertations

Sphingolipids play a crucial role in signaling, membrane structure, and migration, making them important molecules in cancer development, metastasis, and drug resistance. While some sphingolipids have been associated with pro-apoptotic or pro-survival behaviors, the role of many sphingolipids in cancer remains poorly defined. Chapter 1 of this study investigated the impact of three enzymes that compose most of the ceramide to Lc3 ceramide pathway – UGCG, GBA, and B3GNT5 – and how their alteration impacts chemoresistance and basal membrane invasion in vitro. It was found that the CΒE-induced inhibition of GBA, which converts glucosylceramide to ceramide, has no effects on …

The Effects Of Interleukin-1Β On Cardiac Reserve And Exercise Capacity In The Mouse, Habeebah Z. Vohra

Theses and Dissertations

Heart failure (HF) is characterized by dyspnea, fatigue, and exercise intolerance. Clinical evidence points to increased interleukin-1β (IL-1β) activity in patients with HF, with an IL-1 blockade improving the exercise capacity in HF patients. In healthy mice, recombinant-mouse IL-1β (rmIL-1β) induces acute systolic dysfunction, peaking 4 hours after administration. However, the direct effects of rmIL-1β on exercise capacity are unknown. We hypothesized that rmIL-1β diminishes the exercise capacity in the mouse. Adult mice were trained to run on a treadmill and exercise capacity was assessed before, 4 hours, and 96 hours after intraperitoneal administration of rmIL-1β (3 μg/kg) or vehicle …

Health Outcomes And Utilization Associated With Renal Diseases In Patients With Cancer In The United States, Mitisha Dedhia

Theses and Dissertations

Background: Adverse events and impairments associated with cancer and its treatments causes worse outcomes. Increased incidence of renal diseases among cancer patients is of particular concern. Objective: To determine the risk factors for renal disease in cancer patients and compare healthcare costs, utilization and health-related quality of life (HRQoL) of cancer patients with a renal disease and cancer patients without renal diseases. Methods: Medical Expenditure Panel Survey files from 2009 – 2018 for cancer patients was used for this study. Multiple logistic regression, generalized linear model, Poisson regression and multiple linear regression for analyses after adjusting for demographic, socioeconomic and …

Patient Blood Management Programs And Their Association With Patient And Organizational Outcomes, Sandra L. Lamm

Theses and Dissertations

Blood transfusions are the most common hospital procedure. However, many transfusions may be unnecessary. These unnecessary transfusion may expose patients to the potential risks of transfusion without improving patient outcomes Patient blood management (PBM) programs emphasize conserving a patient’s own blood resources and only transfusing the minimum amount needed. This study examined the organizational and environmental factors associated with a hospital having a PBM program, or having processes based on PBM, and their impact on organizational and patient outcomes potentially affected by blood transfusions.

A PBM survey was created for this study and used to gather information on hospitals having …

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 …

The Roles Of Neutralizing Antibodies In Blocking Human Cytomegalovirus Entry Into Multiple Cell Types, Li He

Theses and Dissertations

Human cytomegalovirus (HCMV) can be transmitted through body fluids and cause serious disease in the immunologically immature or immunocompromised population. HCMV entry utilizes different mechanisms involving various viral envelope glycoproteins. gB and gH/gL/gO (trimer) are involved in fibroblast entry and gH/gL/U128-131A (pentamer) is required in addition to trimer for epithelial and endothelial cell entry. gO is heavily glycosylated and highly polymorphic in different HCMV strains. gO in the parental TB40/E strain was completely or partially replaced by gOs from other HCMV strains. A quantitative luciferase-based assay demonstrated that certain polymorphic gOs from different strains can interfere with neutralization of fibroblast …

A Spatiotemporal Assessment Of Fish Assemblage Response To Land-Use Change And The Evaluation Of Edna Metabarcoding For Describing Diverse Fish Communities, Timothy M. Owen

Theses and Dissertations

Fish assemblages are often assessed as a biological proxy for environmental health. While humans value healthy environments for the ecosystem services and recreational opportunities they provide, it is increasingly evident that such resources can be paradoxically degraded by anthropogenic activities. In this investigation, we studied the relationship between different intensities of anthropogenic land-use change and habitat-driven fish assemblage response across multiple spatiotemporal scales. Secondarily, we explored the efficacy of eDNA metabarcoding against conventional electrofishing techniques for the purpose of describing complete fish communities. This study was conducted in the Tuckahoe Creek basin near Richmond, Virginia. This James River tributary serves …

Evaluating The Clinical Utility Of A Novel Electroencephalography System For Assessing Perioperative Neurocognition In Older Surgical Patients, Lloyd H. Barnwell Iii

Theses and Dissertations

Postoperative delirium (POD) is a public health and research priority (American Society of Anesthesiologists, 2019). POD is a risk factor for long-term neurocognitive decline, and the rate of decline is directly proportional to the severity of POD (Vasunilashorn et al., 2018). Baseline cognitive function is a strong, independent predictor for POD (Culley et al., 2017). The International Perioperative Neurotoxicity Working Group recommends baseline cognitive function be assessed for older patients prior to surgery and anesthesia (Berger, et al., 2018). Perioperative cognitive screening tools trialed in anesthesia are not routinely incorporated into clinical practice related to validity, reliability, or practicality problems …

Starting Earnings Of Bachelor’S And Advanced Degree Graduates By Field Of Study: Using Multi-Level Modeling To Estimate The Effects And Early Labor Market Consequences Of Vertical And Horizontal Dimensions Of Higher Education, Qiao Liang

Theses and Dissertations

This study was conducted to better understand early labor market outcomes of higher education and the importance of the vertical and horizontal dimensions of higher education. Using College Scorecard’s institution and field of study levels data and a multilevel modeling approach, it estimated and ranked typical starting earnings associated with a large spectrum of bachelor’s and advanced degree programs, and discussed patterns, variations, and irregularities observed in the ranked earnings. This study also calculated advanced degree effects on the typical starting earnings associated with bachelor’s and advanced degree programs, and set precedence to systematically compare the effects of major, department, …

Breaking The Cycle: A Longitudinal Study Of Factors That Disrupt Peer Selection And Influence Processes Among Urban Youth, Kelly E. Oconnor

Theses and Dissertations

Having friends who engage in problem behavior (i.e., aggression, substance use, delinquency) has consistently been linked to adolescents’ own engagement in problem behavior. There are, however, several key gaps in the literature on peer influence. Few studies have considered the influence of friends’ prosocial behavior and there has been limited research to identify promotive factors that influence urban youths’ affiliation with peers who engage in problem and prosocial behavior across early adolescence, a time of heightened susceptibility to peer influence. The purpose of this study was to identify modifiable promotive factors that reduce adolescents’ problem behavior by decreasing exposure to …

The Influence Of Shifting Learning Environments On Teachers’ Data Use Practices, Stephanie M. Moore

Theses and Dissertations

In March of 2020, schools in the United States closed for in-person learning due to the COVID-19 pandemic. When the school year began in the fall of 2020, many schools continued to operate virtually rather than in-person. In response, many teachers’ practices were revised. Although data use has been widely explored, teachers’ use of data in a virtual environment has received limited attention. This study contributes to the existing knowledge by exploring the influence of the shifting learning environments on the data use practices of teachers in four schools in one school district during the 2020 -2021 school year.

Teachers …

Bayesian Techniques For Relating Genetic Polymorphisms To Diffusion Tensor Images Of Cocaine Users, Tmader Alballa

Theses and Dissertations

Past investigations utilizing Diffusion Tensor Imaging (DTI) have demonstrated that cocaine use disorder (CUD) yields white matter changes. We proposed three Bayesian techniques in order to explore the relationship between Fractional Anisotropy (FA), genetic data, and years of cocaine use (YCU). CUD participants exhibit abnormality in different areas of the brain versus non-drug using controls, which is measured by DTI. This dissertation is motivated by a neuroimaging genetic study in cocaine dependence, which found that there were relationships between several genes such as GAD and 5-HT₂R and CUD subjects.

In the first chapter, there is background on the …

Surface Characterization Of Accident Tolerant Fuel Claddings Candidates After Prolonged Exposure To Steam Oxidation, Connor F. Donlan

Theses and Dissertations

Accident Tolerant Fuel Claddings are designed to improve fuel performance and safety in abnormal reactor conditions. The development of these cladding materials has become a top priority for the nuclear community, with incidents such as the Three Mile Island accident and the Fukashima Dai-chi accident. The development of these claddings has resulted in 2 subsections: coating current claddings or replacing cladding materials with new materials. The claddings studied in this thesis are a Zircaloy-4 cladding coated with chromium through physical vapor deposition, Zircaloy-4, and a FeCrAl alloy, C26M. This thesis assessed the surface chemistry, roughness, and wettability after extended exposure …

Repair In An Economy Of Trauma: How Identifying Traumas As The Basis For Teacher Artmaking Contributes To Resiliency In Managing Traumatic Stress, Danielle R. Houdek

Theses and Dissertations

REPAIR IN AN ECONOMY OF TRAUMA:

HOW IDENTIFYING TRAUMAS AS THE BASIS FOR TEACHER ARTMAKING CONTRIBUTES TO RESILIENCY IN MANAGING TRAUMATIC STRESS

By Danielle Raddin Houdek, BFA, MAE

A thesis submitted in partial fulfillment of the requirements for the degree of Master of Art Education at Virginia Commonwealth University.

Virginia Commonwealth University, 2021.

Major Director: Dr. Sara Wilson-McKay

Associate Professor, Department of Art Education, School of the Arts

Objective: Through this research project, the impact that secondary traumatic stress has on art educators and how artmaking contributes to resiliency in managing secondary traumatic stress was examined. The research question is: …

Identification Of Four Residues Within The Tm4 Of The 5-Ht2a Receptor Necessary For 5-Ht2a·Mglu2 Heteromerization, John Mcginn

Theses and Dissertations

While the etiology is unknown, serotonin and glutamate G protein-coupled receptors (GPCR) neurotransmission dysfunctionality is characteristic of schizophrenia. Previous findings demonstrated that the serotonin 5-hydroxytryptamine 2A (5-HT_2A) receptor and the metabotropic glutamate 2 (mGlu2) receptor assemble into a heteromeric complex; however, little is known of the complete structural interface of the heteromer. Through a mutational-based approach, previous research identified Transmembrane domain 4 (TM4) as being responsible for mediating heteromerization in mGlu2 before determining the particular amino acids responsible for the interface. A similar technique was used in this investigation to determine which component of 5-HT_2A is responsible …

Interclass Gpcr Heteromerization Affects Localization And Trafficking, Rudy Toneatti

Theses and Dissertations

Class A serotonin (5-hydroxytryptamine) 2A (5-HT_2AR) and class C metabotropic glutamate 2 receptors (mGluR2) are seven transmembrane receptors (7TMRs or G protein-coupled receptors – GPCRs) involved in multiple neuropsychiatric disorders including schizophrenia. Previous findings from our laboratory reported that 5-HT_2AR and mGluR2 are dysregulated in the prefrontal cortex of patients suffering from this psychiatric condition, although 5-HT_2AR’s expression was recovered in antipsychotic-medicated patients. Genome-wide association studies on schizophrenia reported that endosomal trafficking that regulates cell surface abundance of another 7TMR implicated in this disease (dopamine D2 receptor) can be altered. Ligand-activated receptors, including the …

The Cb1 Receptor Positive Allosteric Modulator, Zcz011, Attenuates Naloxone-Precipitated Withdrawal Signs In Oxycodone-Dependent Mice And Inhibits Small Intestinal Transit In Mice, Julien Dodu

Theses and Dissertations

The endogenous cannabinoid system tightly regulates a myriad of physiological and pathophysiological functions. Effects of cannabinoids in ameliorating opioid withdrawal signs has been known for decades. Naloxone precipitates several withdrawal signs (e.g., diarrhea, weight loss, jumps, paw flutters, and head shakes) in opioid dependent rodents. ∆⁹-tetrahydrocannabinol (THC) has been shown to ameliorate opioid withdrawal in mice through the activation of cannabinoid type-1 (CB₁) receptors. Inhibition of the endocannabinoid degradative enzymes also attenuates these withdrawal signs (i.e., diarrhea, weight loss, jumps, paw flutters, and head shakes) in opioid-dependent mice. Specifically, inhibition of fatty acid amide hydrolase (FAAH), …

Sickle Cell Disease Associated Lipid Changes And Their Relevance Towards The Disease Pathogenesis And Lipid Biomarkers And Embryo Quality In In Vitro Fertilization; Pregnancy Success Differentially Expressed By Body Weight, Suad Alshammari

Theses and Dissertations

Abstract

Sickle cell disease (SCD) is a group of genetic disorder that occurs due to genetic mutation of a beta-globin gene that lead to production of pathogenic hemoglobin S (HB S). Genotypes of SCD include Hb SS (sickle cell anemia) which is the most common and severe form of SCD affects about 20 to 25 million people worldwide, HbSC, Hb Sβ+- thalassemia, and Hb Sβ0-thalassemia. SCD is characterized by multiorgan complications that, in turn, affect lipids composition. During hypoxia a sequence of changes will take place such as HbS polymerization, erythrocyte rigidity and stickiness, and oxidative stress. The combination of …

Nebulizer-Based Systems To Improve Pharmaceutical Aerosol Delivery To The Lungs, Benjamin M. Spence

Theses and Dissertations

Combining vibrating mesh nebulizers with additional new technologies leads to substantial improvements in pharmaceutical aerosol delivery to the lungs across therapeutic administration methods. In this dissertation, streamlined components, aerosol administration synchronization, and/or Excipient Enhanced Growth (EEG) technologies were utilized to develop and test several novel devices and aerosol delivery systems. The first focus of this work was to improve the poor delivery efficiency, e.g., 3.6% of nominal dose (Dugernier et al. 2017), of aerosolized medication administration to adult human subjects concurrent with high flow nasal cannula (HFNC) therapy, a form of continuous-flow non-invasive ventilation (NIV). The developed Low-Volume Mixer-Heater (LVMH) …

Effect Of Kcc2-Enhancing Prodrug Clp290 On Tat ± Morphine Treated Female Mice At The Behavioral And Molecular Levels, Michael Marone

Theses and Dissertations

HIV-1 infection is highly comorbid with opioid use disorder. Prescription and illicit use of opioids are particularly risky for HIV-1 infected individuals due to potential synergistic neurotoxic effects mediated by viral proteins and opioids. Additionally, opiate drug abuse has been shown to exacerbate neuropathogenesis of HIV-1⁺ individuals. Development of combination antiretroviral therapies (cART) has drastically improved the life expectancy of these patients. Unfortunately, although the severity of neurological and neurocognitive complications has declined, the incidence of HIV-associated neurocognitive disorders (HAND) remains 30-50% in the post-cART era and is worsened by opioid use disorder. HIV-1 proteins, inflammatory mediators, and excitotoxins …

The Importance Of Connection: Contributions Of Relationships With Fathers And Connections To School To Delinquent Behavior And Positive Youth Development, Colleen S. Walsh

Theses and Dissertations

Risk-taking and boundary pushing are hallmarks of adolescent behavior, making the identification of promotive and protective factors related to both delinquent behavior and positive adolescent functioning essential. Previous studies have provided compelling evidence that suggests aspects of familial relationships may successfully attenuate delinquent behavior and support positive functioning outcomes. Despite these findings, the father-adolescent relationship is understudied in association with these outcomes. The current study examined relations between adolescents’ perception of school connectedness and father-adolescent relationship quality and delinquent behavior and positive adolescent functioning outcomes. This study used data collected when youth were nine and fifteen years old from the …

Development And Evaluation Of A Combinatorial Rt-Qpcr Multiplex For Forensic Body Fluid Identification, Carolyn A. Lewis

Theses and Dissertations

Body fluid identification is essential in the forensic biology workflow that assists DNA analysts in determining where to collect DNA evidence. Current presumptive tests lack the sensitivity and specificity molecular techniques can achieve; therefore, molecular methods, such as microRNA and microbial signatures, have been extensively researched in the forensic community. Limitations of each method suggest combining molecular markers to increase discrimination efficiency of multiple body fluids from a single assay. While microbial signatures have been successful in identifying fluids with high bacterial abundances, microRNAs have shown promise in fluids with low microbial abundance. A disadvantage of RNA analysis in forensic …

Comparing The Sensitivity And Specificity Of Cbct And Mri In Detecting Osteoarthritis Of The Tmj: A Systematic Review, Gabriel R. Saavedra

Theses and Dissertations

The aim of this systematic review was to compare the sensitivity and specificity of cone-beam computed tomography (CBCT) and magnetic resonance imaging (MRI) in detecting osteoarthritis (OA) of the temporomandibular joint (TMJ). This was done by using computed tomography (CT) and the research diagnostic criteria for temporomandibular disorders (RDC/TMD) as reference methods and using CBCT and MRI as index methods. A specific search strategy was developed and applied to these electronic databases: PubMed, Embase, DOSS, and Cochrane. The search results returned 802 articles, which were then narrowed down using the inclusion/exclusion criteria, to four final articles that were included in …

The Organizational Commitment Of Sonographers In The Mid-Atlantic Region Of The United States, Yonella Demars

Theses and Dissertations

Sonographers are skilled medical professionals who operate specialized equipment that utilizes sound waves to create images of the body. Radiologist and physicians depend on sonographers to summarize their findings by creating a preliminary report that is sent, along with images, to them for diagnosis and treatment purposes.

Organizational commitment is described by John Meyer and Natalie Allen, through their organizational commitment three component model, as a mindset reflecting a desire, a need, or obligation to maintain membership in an organization. Specifically, affective organizational commitment is the desire an employee demonstrates that allows them to remain with their employer because of …

An Examination Of The Impacts Of Childhood Trauma On Healthy Intimate Relationships In College-Aged African Americans, Broquelynn D. Shepard

Theses and Dissertations

For African Americans, the dynamics of relationships are rooted in childhood experiences of unconditional love, restraint, and respect. These experiences help individuals form their understanding of how relationships function. Experiencing healthy relationships has an enduring impact on social development and interpersonal relationships. However, regarding studies on childhood trauma and intimate relationships, there is insufficient literature that includes African American samples as the primary foci of the research. Due to gaps in extant literature, the present study aims to explore whether experiences of healthy intimate relationship in African Americans are associated with childhood trauma (neglect, emotional, sexual, and physical abuse). Using …

Courts Beyond Judging, Michael C. Pollack

Articles

Across all fifty states, a woefully understudied institution of government is responsible for a broad range of administrative, legislative, law enforcement, and judicial functions. That important institution is the state courts. While the literature has examined the federal courts and federal judges from innumerable angles, study of the state courts as institutions of state government — and not merely as sources of doctrine and resolvers of disputes — has languished. This Article remedies that oversight by drawing attention for the first time to the wide array of roles state courts serve, and by evaluating the suitability of both the allocation …

Defining Who Is An Employee After A.B.5: Trading Uniformity And Simplicity For Expanded Coverage, Edward A. Zelinsky

Articles

My assessment of California’s A.B.5 differs from the evaluation advanced by the advocates and opponents of that legislation: I conclude that A.B.5 made a significant but limited expansion of the coverage of California labor law but at a notable cost. Even as A.B.5 broadened the reach of the Golden State’s labor protections, A.B.5 also made the definition of "employee” more complex and less uniform. Those seeking federal or state legislation like A.B.5 confront the same trade-off under which greater coverage is achieved at the expense of more complexity and less uniformity in the definition of who is an employee. The …