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Characterization Of The Gonococcal Calprotectin Zn-Acquisition System, Tdfh, And The Efficacy Of Metal Starvation For Treating Gonococcal Disease, Michael T. Kammerman

Theses and Dissertations

Abstract

Characterization of the Gonococcal Calprotectin Zn-Acquisition System, TdfH, and the Efficacy of Metal Starvation for Treating Gonococcal Disease.

By Michael T. Kammerman, B.S.

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

Virginia Commonwealth University, 2020

Major Director: Cynthia Nau Cornelissen, Ph.D.

Professor, Department of Microbiology and Immunology

Neisseria gonorrhoeae, the bacterial agent that is responsible for the human disease gonorrhea, has had a steady increase in the number of infections per year. In 2018 the WHO estimated over 87 million infections occurred world-wide, and the CDC …

The Effect Of The Senolytic Abt-263 On Androgen Deprivation-Induced Senescent Prostate Tumor Cells, So Min Lee

Theses and Dissertations

Prostate cancer (PCa) is one of the leading causes of cancer-related deaths in men. Although standard treatments such as androgen deprivation therapies (ADT) and antiandrogens have increased survival for many patients, most men placed on these therapies will develop castration-resistant disease (CRPC). Previous studies have shown that these treatments have limited cytotoxicity and instead promote cell growth arrest. Our current work demonstrates that prostate tumor cells grown in the absence of androgens by using charcoal-stripped serum undergo senescence-mediated or senescent-like growth arrest, based on the cellular expression of senescence-associated-beta-galactosidase (SA-β-Gal). Our studies further suggest that this senescence is transient and …

Reducing Disparities In Smoking For Adults With Mental Illness: Are U.S. Tobacco Prevention Policies Effective?, L. Morgan Snell

Theses and Dissertations

One in five people in the U.S. are estimated to experience “any mental illness” (AMI); however this group represents an estimated 40% of the annual, adult cigarette consumption in the U.S. Tobacco prevention policies have been successful at reducing smoking prevalence among the U.S. population as a whole, however it is unclear whether these efforts have had significant impact on tobacco use rates among individuals with AMI. The three papers that comprise this project combined longitudinal, nationally-representative data and online behavioral experiments from U.S. adults to compare demand for cigarettes among adult smokers with and without AMI. Taken together, our …

Investigation Of Molecular Mechanisms Of Liver Preservation Injury: A Complication Preceding Organ Transplantation, Ria C. Fyffe-Freil

Theses and Dissertations

Of the over 108,000 American awaiting a life-saving organ transplant today, over 12,000 (11%) of those need a new liver (OPTN, 2020). Last year, only 35% of patients on the waiting list for an organ were transplanted. Improving the quality of marginal organs by preventing or reversing preservation injury could vastly increase the number of transplants performed. Washout of circulating blood during liver procurement with cold University of Wisconsin solution flushes out any endogenous pro-survival signaling molecules. We investigated lysophospholipid (LPL) surface receptors (G-protein coupled receptors for lysophosphatidic acid (LPA) and sphingosine- 1-phosphate (S1P)) and their role in protecting hepatocytes …

3-D Homology Modeling Of Organic Anion Transporters (Oats): Defining The Biochemical Basis For Oat-Substrate Interactions, Christopher Jay

Theses and Dissertations

A goal in the drug development process, as indicated by the FDA, is to evaluate a drug’s ADME profile, as potential drug interactions could exist, leading to adverse drug reactions or loss of efficacy. Transport proteins, specifically organic anion transporters (OATs) are involved in the absorption, distribution, and elimination of small, negatively charged compounds. Although there is an exhaustive list of structurally diverse organic anions which interact with OATs, interactions at a molecular level are still shrouded in mystery particularly due to the lack of a solved crystal structure. Therefore, in silico homology models (hOAT1, 2, 3) were generated using …

The Effect Of Intermittent Theta Burst Stimulation On Biceps Corticomotor Excitability In Non-Impaired Individuals And Individuals With Tetraplegia, Blaize Majdic

Theses and Dissertations

Neuromodulation of the primary motor cortex (M1) in pair with physical therapy may be a promising method for improving motor outcomes after spinal cord injury (SCI). Increased excitability of the corticospinal motor pathways (i.e. corticomotor excitability) has shown to be associated with improved motor learning and skill acquisition. Intermittent theta burst stimulation (iTBS) is a form of non-invasive brain stimulation which can increase corticomotor excitability, as measured by an increase in the amplitude of motor evoked potentials (MEPs). However, the ability for iTBS to increase the corticomotor excitability of proximal muscles such as the biceps, and muscles affected by spinal …

Process Factors Affecting Reperfusion Time In Patients Presenting With St-Segment Elevation Myocardial Infarction (Stemi), Richard R. Wall

Theses and Dissertations

Abstract PROCESS FACTORS AFFECTING REPERFUSION TIME IN PATIENTS

PRESENTING WITH ST-SEGMENT ELEVATION MYOCARDIAL INFARCTION (STEMI) By Richard R. Wall MSRS, RT(R)(CT)(CI), RCIS

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

Virginia Commonwealth University, 2020.

Dissertation Chair: Jeffrey S. Legg Ph.D. Associate Professor and Chair, Department of Radiation Sciences

An ST-segment myocardial infarction (STEMI) occurs when the blood flow to the myocardium is suddenly and completely blocked causing the myocardium to become ischemic. A STEMI is a life-threatening condition that necessitates emergent medical treatment. Research has shown that longer …

The Effects Of Exosomes On The Regeneration Of Rat Calvaria, Jill T. Beitz

Theses and Dissertations

Periodontal disease is a bacterial induced chronic inflammatory condition that occurs in a susceptible host, affecting the teeth, gingiva, periodontal ligament, and alveolar bone. The resultant pathological bone defects often require surgical intervention, with the ultimate goal being regeneration of the periodontium through the application of grafting materials and biologics. Mesenchymal stem cells (MSCs) show great potential in regenerative medicine for their ability to enhance cell proliferation and differentiation, increase angiogenesis, and modulate the immune response. Stem cell-derived by-products, known as exosomes are a specific class of lipid-membrane-bound extracellular vesicles that are proliferative and chemotactic, are able to inhibit cytokine …

Kcc2: A Novel Therapeutic Target To Rescue Gabaergic Dysfunction And Behavioral Deficits Induced By Hiv And Opiate Use, Aaron J. Barbour

Theses and Dissertations

With adherence to combined antiretroviral therapy (cART), HIV infection can be considered a controllable chronic condition, but quality of life issues remain. The preeminent of which, HIV-associated neurocognitive disorders (HAND), encompasses an array of neurological complications and has persisted despite cART implementation. The symptoms of HAND can be exacerbated by opiate use, a common comorbidity for people infected with HIV (PWH). While neurons are not infected by HIV, they incur sublethal damage, with γ-amino butyric acid- (GABA)ergic function being particularly vulnerable to viral and inflammatory factors released by infected/affected glia. This dissertation presents studies on novel organoid and dissociated primary …

“Is Therapy For Me?” Perceptions Of Therapy Inclusivity And Willingness To Seek Help Among Black Emerging Adults, Randl B. Dent

Theses and Dissertations

Mental health issues are prevalent among Black emerging adults; however, they tend to underutilize mental healthcare services. The goals of the current study were to examine whether: (1) perceived therapy inclusivity would predict willingness to utilize mental healthcare services and (2) the relationship between perceived therapy inclusivity and willingness would be moderated by two indices of racial identity (i.e., centrality and private regard). Results provide evidence that greater perceptions of therapy inclusivity are associated with greater willingness to seek mental health services even after controlling for factors, such as gender, self-stigma, and previous mental healthcare utilization. Additionally, there was no …

Comparison Of Endodontic Treatment Planning Decisions Using Cone Beam Computed Tomography Versus Periapical Radiography In Previously Endodontically Treated Molars, Sarah Alkanderi

Theses and Dissertations

Objectives: The aim of this study was to determine if treatment plans differ when evaluating previously endodontically treated molars using periapical images (PA’s) alone versus PA’s and CBCT.

Methods: A retrospective cohort chart review was conducted including 67 previously treated molars that had a CBCT taken. Two calibrated board-certified endodontists evaluated standard PA’s. A data sheet questionnaire regarding radiographic findings and treatment plan decisions was completed. Two weeks later, the same steps were repeated but the examiners evaluated both PA’s and CBCT images and again arrived at a recommended treatment plan.

Results: Agreement between raters was assessed with Cohen’s Kappa …

Current Trends In The Management Of Invasive Cervical Resorption, Erik J. Foisy

Theses and Dissertations

Purpose: To determine how endodontic practitioners are currently managing cases of invasive cervical resorption. Also, to analyze how invasive cervical resorption (ICR) has been managed at Virginia Commonwealth University (VCU) over the past ten years.

Methods: Both domestic and international endodontists were invited to participate in a 14-question survey developed and administered via REDCap. Survey invitations were sent via email to currently practicing endodontists. Electronic dental records were queried for patients diagnosed with ICR at VCU in the preceding ten years. Results of both were summarized using descriptive statistics (counts and percentages). Fisher’s exact test was used to compare survey …

Characteristics Of Alveolar Bone Marrow Cells From Patients Undergoing Dental Extractions Or Dental Implant Therapy, Meng H. Lee

Theses and Dissertations

Alveolar bone marrow stromal cells (aBMSCs) play important roles in craniofacial wound healing. To establish an easy, efficient and reliable method to harvest aBMSCs, we compared three different methods: extraction socket aspiration, osteotomy aspiration and bone core digestion. Samples of aBMSC were collected from two groups of subjects. Group 1 (dental extraction): after dental extraction, 22.5-gauge needles were used to collect 0.5-1cc marrow aspirate. Group 2 (dental implant): during implant surgeries, bone core and 0.5-1cc marrow aspirate were obtained from the osteotomy. Samples were cultured in petri dishes and attached cells were expanded. The population doubling time (PDT), surface markers, …

A Comparison Of Three-Dimensional Printing Technologies On The Precision, Trueness, And Accuracy Of Printed Retainers, Owais A. Naeem

Theses and Dissertations

Purpose: The aim of this study was to evaluate the differences in the precision, trueness, and accuracy of 3D printed orthodontic clear retainers produced using printer systems with various printing technologies.

Methods: Retainers (n=15) were printed using four different 3D printers: a stereolithography (SLA) printer, two different digital light processing (DLP and cDLP) printers, and a polyjet photopolymer (PPP) printer. The 3D printed retainers were transformed into a digital file through a cone-beam computed tomography scan that was compared to the original image using a 3D superimposition analysis software. At previously chosen landmarks (R6, L6, R3, L3, R1, L1) retainers …

The Relationships Among External Environments, Organizational Structures, And Performance In Pursuit Of The Clinical And Academic Missions At Academic Health Centers, Eric J. Strucko

Theses and Dissertations

Clinical and academic missions place Academic Health Centers (AHCs) at the center of the American health care system, and the future viability of these institutions requires successful performance in competitive environments. AHCs are organizations involving hospitals, physician group practices, and medical schools, and treat patients with complex conditions, conduct bio-medical and health science research, and educate future physicians and health professionals. AHCs account for 20% or $540 billion of national health care expenditures, conduct over 80% of all heart, liver, and lung transplants, utilize over $27 billion in annual sponsored research funding, and graduate approximately 17,300 medical doctors annually. Financial …

The Effect Of Print Angulation On The Accuracy And Precision Of 3d-Printed Orthodontic Retainers, Allison Williams

Theses and Dissertations

Purpose: The aims of this study were: 1) to compare the accuracy and precision of 3-

dimensional (3D) printed retainers at various angulations, 2) to evaluate the effect of angulation

on printing time and the amount of resin consumed.

Methods: Using a stereolithography (SLA) 3D printer, a total of 60 clear retainers were printed at five angulations (n=12, each): 15, 30, 45, 60, and 90 degrees. Six retainers were printed each cycle at a random order for all print angulations as print 1 and print 2. Digital images of the original and printed retainers were superimposed. Discrepancies on eight landmarks …

Achieving Dentin Conservation Using Dynamic Navigation Technology For Locating Calcified Canals, Madison W. Saunders

Theses and Dissertations

Purpose: Pulp canal obliteration (PCO) is a common sequela of dental trauma, caries, restorations and vital pulp therapy procedures. Despite the application of high magnification and CBCT imaging, access cavity preparation for such cases is prone to procedural errors that may lead to substantial loss of dentin structure thereby reducing the long-term prognosis. This study aimed to achieve dentin conservation using a novel computer assisted dynamic navigation system (Navident) in comparison to freehand access preparation for locating calcified canals.

Methods: Forty maxillary and mandibular central incisors (tooth #9 and tooth #25) were 3-D printed to simulate PCO. They were randomly …

The Effects Of Autophagy And Senescence On Sensitivity To Cisplatin In Head And Neck Cancer, Zara H. Siddiqui

Theses and Dissertations

While current treatments in cancer, such as chemotherapy and radiation, can generally be effective in eliminating disease in patients, there also exists the possibility of recurrence of cancer cells over time. In patients diagnosed with locally advanced head and neck carcinoma, about 50-60% develop a loco-regional recurrence within two years, and 20-30% of patients develop metastatic disease at distant sites in the body [5]. On a cellular level, one mechanism for this survival may be that natural mechanisms such as autophagy and senescence play a role in allowing cells to survive after undergoing treatment. One standard of care chemotherapy for …

Effects Of (R,S)-Ketamine And (2r,6r)-Hydroxynorketamine: A Preclinical Study, Remington Rice

Theses and Dissertations

In 2017, 7.1% of US adults were diagnosed with depression, and 50% of patients received medication to treat their depression. Depression can cause severe interruptions in an individual's cognitive functioning and behaviors like sleeping, eating, working, and socializing. Unfortunately, approximately 40% of patients do not respond to treatment with monoaminergic medications (e.g. Prozac) and therapeutic effects may be delayed 2-8 weeks. Due to these therapeutic shortcomings, faster acting and more efficacious treatments are needed. Recent preclinical findings indicate potential for glutamatergic drugs like (R,S)-ketamine and (2R,6R) hydroxynorketamine to produce more rapid and longer-acting therapeutic effects. The antidepressant effectiveness of (R,S)-ketamine …

Amixicile As A Novel Antimicrobial Treatment For Periodontitis: A Pilot Study In The Non-Human Primate, Macaca Mulatta, Denver J. Lyons

Theses and Dissertations

Periodontitis is an inflammatory disease with a bacterial etiology in a susceptible host. Given the bacterial etiology, a selective antimicrobial agent with minimal side effects could be a useful adjunct to traditional therapy. Amixicile is a novel antimicrobial that targets the pyruvate: ferredoxin oxidoreductase (PFOR) which is an enzyme that is critical for anaerobic bacterial metabolism. It has been found to have no effect on commensal, aerobic microbes and has little to no side-effects thus far in animal models. In this study, two nonhuman primates of the Macaca mulatta species with naturally occurring mild chronic periodontitis were studied before and …

From Bedside To Bench: Use Of Patient-Derived Xenograft Models To Develop Novel Therapeutic Strategies For Triple-Negative Breast Cancer, Tia H. Turner

Theses and Dissertations

Triple-negative breast cancer (TNBC) is a clinically aggressive disease that is associated with bleak outcomes due to its metastatic propensity, frequent failure to respond to chemotherapy, and lack of alternative treatment options. Despite decades of major translational research efforts, there has been very little success thus far in the development of effective targeted therapies for this disease. It is imperative to develop novel therapeutic strategies to improve patient outcomes, as well as minimize the toxicity associated with standard-of-care chemotherapeutics. Given that metastatic disease accounts for the vast majority of TNBC-related deaths, a better understanding of therapeutic responses within common sites …

Effects Of Gestational Ozone Exposure On Privileged Placental And Brain Barrier Integrity, Alexander I. Hamm

Theses and Dissertations

Ambient outdoor ozone, a common of component of photochemical smog and urban air pollution, is linked to various neurological and vascular pathologies. Its immediate reaction with lung surfactant after inhalation results in complete reactivity of the gas, with no active ozone passing into circulation. This indicates the presence of secondary and tertiary mediators in ozone-related systemic pathologies after pulmonary insult. In vasculature, ozone exposure is associated with an acute hypertensive phenotype apparent at least 24 hours after dose, such as experienced on a hot summer afternoon in a large metropolitan area like Los Angeles or Mexico City. However, the effects …

Swipe Right For Condoms And Testing: Differences In High-Risk Sexual Behavior And Sexual Health Beliefs Among Dating App Users Compared To Non-App Users, Shelby A. Smout

Theses and Dissertations

Millions of Americans are currently using smartphone dating applications (apps) to socialize and meet with others. In some cases, app-based conversations lead to sexual interactions. Previous research examining the relationship between the use of dating apps and sexual behaviors has found that individuals who use dating apps and meet with partners from the app are more likely to engage in high-risk sexual behaviors such as having multiple partners and inconsistent condom use. Individuals between the ages of 18 and 24 are the group most likely to be using dating apps compared to other age groups and are a high-risk group …

Associations Between Stress, Racial Discrimination, And Cytokine Levels In Black Americans, Takia Williams

Theses and Dissertations

Inflammation is a common pathophysiological pathway for a number of chronic diseases and is influenced by exposure to stress. Although there are racial disparities in health outcomes, relatively little is known about factors that may influence the inflammatory response in Black American individuals. This study examined whether racial discrimination and other forms of stress are associated with the balance of pro- and anti- inflammatory cytokines in Black American adults. Data from 22 participants were drawn from a larger study of Black American children (ages 5-12) and their primary caregivers drawn from low income neighborhoods in Richmond, Virginia. Caregivers reported demographics, …

The Correlation Between Maternal Postpartum Depression And Child Psychopathology, T'Keyah I. Vaughan

Theses and Dissertations

Background: Postpartum depression (PPD) is a phenomenon that affects nearly 10-15% of pregnancies in the US. It is characterized by depressed mood or anhedonia and lasting for more than 2 weeks. PPD changes how moms interact with family members and child-rearing behavior. Depression is a phenomenon that is also known to affect the psychopathology of children. However, the specifics of how postpartum depression impacts children remains controversial. Many studies do not control for major depressive disorder which makes it difficult to disentangle the impact depression has within the first year of life. Furthermore, other PPD risk factors may be confounding …

The Impact Of Aging And Mechanical Injury On Alveolar Epithelial And Macrophage Responses In Acute Lung Injury And Inflammation, Michael S. Valentine

Theses and Dissertations

Patients with severe lung pathologies, such as Acute Respiratory Distress Syndrome (ARDS), often require mechanical ventilation as a clinical intervention; however, this procedure frequently exacerbates the original pulmonary issue and produces an exaggerated inflammatory response that potentially leads to sepsis, multisystem organ failure, and mortality. This acute lung injury (ALI) condition has been termed Ventilator-Induced Lung Injury (VILI). Alveolar overdistension, cyclic atelectasis, and biotrauma are the primary injury mechanisms in VILI that lead to the loss of alveolar barrier integrity and pulmonary inflammation. Stress and strains during mechanical ventilation are believed to initiate alveolar epithelial mechanotransduction signaling mechanisms that contribute …

Data Science Methods For Standardization, Safety, And Quality Assurance In Radiation Oncology, Khajamoinuddin Syed

Theses and Dissertations

Radiation oncology is the field of medicine that deals with treating cancer patients through ionizing radiation. The clinical modality or technique used to treat the cancer patients in the radiation oncology domain is referred to as radiation therapy. Radiation therapy aims to deliver precisely measured dose irradiation to a defined tumor volume (target) with as minimal damage as possible to surrounding healthy tissue (organs-at-risk), resulting in eradication of the tumor, high quality of life, and prolongation of survival. A typical radiotherapy process requires the use of different clinical systems at various stages of the workflow. The data generated in these …

Exploring The Use Of Pulsed Erbium Lasers To Retrieve A Zirconia Crown From A Zirconia Implant Abutment, Ahmed Elkharashi

Theses and Dissertations

Removal of zirconia crowns, commonly used as cement-retained implant fixed restorations, can be challenging. Conventional methods of crown removal are time consuming and often leave irreparable damage to the crown, which can be costly to patients and practitioners. This research explored the use of two different types of pulsed erbium lasers, erbium-doped yttrium aluminum garnet laser (Er:YAG) and erbium, chromium-doped yttrium, scandium, gallium and garnet (Er,Cr:YSGG), as non-invasive tools to retrieve cemented zirconia crowns from zirconia implant abutments. Times needed to remove the crowns were recorded and analyzed using ANOVA (��=0.05). No statistical differences between the debond times of each …

The Role Of Patient Room-Type, Interruptions, And Intrapersonal Resources In Nurse Performance And Well-Being, Jennifer Early

Theses and Dissertations

Interruptions create a complex challenge in health care. Because some interruptions are necessary in health care, they cannot be completely eliminated. Thus, their effects must be appropriately mitigated. To better understand predictors and consequences of interruptions, as well as factors that may mitigate their negative effects, I employed Job Demands-Resources (JD-R) theory, supplemented by additional constructs from organizational behavior and psychology to develop a model of predictors and mitigators of interruptions. Twenty registered nurses providing care on a progressive acute care unit with single- and double-occupancy patient rooms volunteered to participate in this study. The study incorporated nurse-level questionnaires, event-level …

Non-Invasive Retrieval Of Prefabricated Zirconia Crowns With Er,Cr:Ysgg Laser From Primary And Permanent Teeth, Connor W. Mccall Dds

Theses and Dissertations

Purpose: Compromised tooth structure on permanent and deciduous teeth in the pediatric population is increasingly being restored with tooth-colored prefabricated zirconia crowns. These restorations may need to be removed or replaced with permanent crowns. The purpose of this in vitro study was to explore the use of an Er,Cr:YSGG laser for removal of prefabricated zirconia crowns cemented with RMGI as a non-invasive alternative to rotary instruments.

Methods: Thirteen permanent and 12 primary molars were prepared to dentin and prefabricated zirconia crowns were passively fitted and cemented with two resin modified glass ionomer cements. The irradiation parameters for ErCR:YSGG were 4.5 …