Medicine and Health Sciences Commons^™

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 …

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 …

Strategies And Devices For Improving Respiratory Drug Delivery To Infants And Children With Cystic Fibrosis, Karl Bass

Theses and Dissertations

Cystic Fibrosis (CF) is a degenerative disease, which causes thickening of the airway surface liquid and reduced mucociliary clearance, which provides an ideal habitat for bacterial infections. Early treatment of CF in children can prevent chronic infection, improve quality of life, and increase life expectancy. The most predominant bacteria found in CF-diseased lungs is Pseudomonas aeruginosa (Pa), which can be treated with inhaled tobramycin. Excipient enhanced growth (EEG) powder formulations are well suited for administering tobramycin to children, as the EEG approach provides minimal upper airway loss and targeted drug delivery. This method uses an initially small aerosol for high …

New Persistent And Chronic Opioid Use In Cancer Survivors After Curative Intent Radiation, Elena V. Fernández

Theses and Dissertations

Background: Emerging evidence suggests that as more patients are surviving cancer, new persistent opioid use (no prior exposure to opioids before cancer therapy but requiring opioid prescriptions after curative intent treatment; NPOU) is of greater concern. In patients receiving curative intent radiation (definitive radiation therapy and as treatment for cure; CIR), the extent to which patients develop NPOU or continue opioid use (COU) following CIR is not known. Neither are factors associated with NPOU or COU, opioid doses, or time to discontinuation (TTD) of opioids in 5CS known. Objectives: Describe longitudinal trends opioid use in cancer survivors who received CIR, …

Model-Based In-Vitro Pk/Pd Profiling Of Novel Synthetic Allosteric Effectors Of Hemoglobin (Aeh) As Potential Sickle Cell Disease (Scd) Therapeutics, Xiaomeng Xu

Theses and Dissertations

Introduction: Allosteric effectors of hemoglobin (AEH) represent a class of synthetic aromatic aldehydes that transiently form covalent interactions (Schiff-base) with hemoglobin (Hb) to form Hb-AEH adduct, preventing the HbS polymerization and sickling of red blood cells (RBC). The overall objective of this research was to aid in the optimization of novel AEH by understanding their target-site disposition of AEH in relevant biological matrices, e.g., HbA solution, whole blood (WB) and human liver cytosol (HLC), a surrogate of aldehyde dehydrogenase (ALDH)-mediated oxidative metabolism.

Methods: A “universal” HPLC-UV/Vis assay method was developed for the quantitation of HbA-AEH adduct for chemically …

Differential Identification Of Hyperacusis And Misophonia: Implications Of Discrete Decreased Sound Tolerance (Dst) Condition Subtypes, Rachel E. Wallace

Theses and Dissertations

Hyperacusis and misophonia are two conditions of decreased sound tolerance (DST) studied in the psychological literature due to their association with psychological symptoms and mechanisms. DSTs are differentiated from normal sound sensitivity due to the reported impairment and distress individuals experience. Researchers suggest that DSTs are differentiated by types of sounds and emotional reactions elicited, such that hyperacusis is a fear and pain response to ordinary environmental sounds perceived as uncomfortably loud, and misophonia is an anger and disgust response to human-made sounds, but these distinctions, and associated characteristics, have not been empirically demonstrated. Undergraduate students (N = 1572) …

Transcriptomic Profiling Of Postmortem Prefrontal Cortex And Nucleus Accumbens From Chronic Alcohol Abusers., Eric S. Vornholt

Theses and Dissertations

Alcohol use disorder (AUD) is a debilitating psychiatric illness that develops from a combination of genetic and environmental factors. While it is well documented that AUD is heritable, the shift from recreational alcohol use to abuse/dependence is poorly understood. In this dissertation, using postmortem brain tissue from individuals with alcohol dependence (AD), we profiled the genome-wide expression of circular RNA (circRNA), microRNA (miRNA), and messenger RNA (mRNA) to better understand the impact of gene expression on the development of AUD. To achieve this, we performed two independent studies that explore transcriptome differences between AD cases and controls. The first of …

The Quantified Elf, Umico Niwa

Theses and Dissertations

The Quantified Elf is an ongoing collection of scientific, medical, archaeological articles and excerpts from my personal journal. It is a way by which I explore the various ways Western notions of personhood subsume human life into constructs of sexuality and gender, overlooking the various other modes of unbridled existence: plant, microbial. fungal, animal, celestial bodies. The speculative medical papers propose novel forms of body modification to combat gender dysphoria.

Can School Be A Source Of Trauma? Assessing Academic Traumatic Stress As A Mechanism Underlying The Health Outcomes Of Black Undergraduate Students, Ebony A. Lambert

Theses and Dissertations

Research examining Black students’ school experiences demonstrates that exposure to oppressive power dynamics in schools may lead to adverse physiological and psychological consequences. Recent conceptualizations in public discourse further posit that traumatic educational experiences, operationalized here as academic trauma or the cumulative toll of adverse and oppressive experiences in academic settings, may influence Black students’ wellbeing even after they have graduated. However, academic trauma has yet to be investigated empirically, and the health contributions of such educational harm remain unstudied. Moreover, little is known about how culturally-relevant personal characteristics (e.g., emotion regulation strategies) influence Black students’ reactivity to academic trauma. …

Impact Of Performance-Based Budgeting On Quality Outcomes In U.S. Military Healthcare Facilities, Kimberly L. Decker Virginia Commonwealth University

Theses and Dissertations

Performance-based budgeting (PBB) is a variation of pay for performance that is applicable to government programs. It works by increasing or decreasing funding based on pre-established performance thresholds, which incentivizes organizations to improve performance. In late 2006, the U.S. Army implemented a PBB program in all of its healthcare facilities due to rising concerns over costs and quality in its facilities. The U.S. Army’s PBB program tied hospital-level funding decisions to performance on key cost and quality-related metrics. This study examined the impact of this program and a subsequent PBB program on quality improvement in U.S. Army healthcare facilities. Drawing …

An Identification Of Tgf-B'S Role In Ischemic Cholangiopathy, Courtney Chmielewski

Theses and Dissertations

Organ transplants are a necessary intervention for many diseases that result in end stage organ failure. The donation pool cannot match the demands of the transplant list, so expanding the pool to include donation after cardiac death (DCD) is desired. However, there are increased odds of graft failure and ischemic cholangiopathy leading to inferior outcomes when DCD livers are used. Ischemic cholangiopathy consists of multiple diffuse strictures and fibrosis of the bile ducts leading to a loss of epithelialization and fibrosis. The cellular mechanism is proposed to be epithelial-to-mesenchymal transition (EMT). TGF-�� is seen as a key initiator of EMT, …

Modeling Gardnerella Host-Pathogen Interaction: Characterization Of Vaginolysin And The Opacity Phenotype, Erin M. Garcia

Theses and Dissertations

Bacterial vaginosis (BV) describes a dysbiotic state of the vaginal mucosa, during which the dominance by beneficial lactobacilli species is lost, the vaginal pH increases, and the flora comprising the vaginal microbiome becomes more diverse. Bacterial taxa associated with this dysbiotic state interact to form a dense polymicrobial biofilm on the surface of the vaginal epithelium. This shift in the vaginal microflora is clinically important, even when symptoms are not noted, as women with BV are at increased risk for acquisition of other sexually transmitted infections, including HIV, and are more than two times as likely to experience preterm birth. …

Spag17 Is Important For Protein Trafficking In Mammalian Spermiogenesis, Virali Bhagat

Theses and Dissertations

Spermiogenesis is the process through which undifferentiated germ cells develop into mature spermatozoa. While spermiogenesis is a very well-regulated process, the protein-protein interactions regulating it remain poorly understood. A knockout (KO) mouse for the ciliary protein SPAG17 was generated by our lab. Loss of SPAG17 has been shown to disrupt the transport of proteins important for acrosome biogenesis and manchette functions. With this information, we hypothesized that SPAG17 plays an essential role in protein trafficking during mammalian spermiogenesis. To further investigate this, immunofluorescence (IF) studies were performed in germ cells collected from both WT and SPAG17 KO mice to visualize …

Hospital Investment In Urgent Care: Impacts On Emergent, Outpatient, And Ambulatory Surgery Volumes, Hillary A. Linhart

Theses and Dissertations

As the popularity of urgent care centers (UCCs) has grown, hospitals have increasingly chosen to invest in this care model. Hospital interest in UCCs is largely driven by two key factors. First, hospitals aim to use UCCs to generate referrals, which generate additional patient volume for downstream hospital services. Secondly, hospital UCC investment presents an opportunity to ease the demand for non-urgent care in the emergency department (ED) by diverting low-acuity ED patients to the more appropriate UCC setting. No study to date has evaluated the impact of hospital UCC investment on referrals or downstream service volumes. A few studies …

An Exploration In Accountable Care Organization Structure, Contingency And Performance, 2015-2017, Siriporn P. Satjapot

Theses and Dissertations

The Patient Protection and Affordable Care Act of 2010 enacted one of the most significant reforms seen in the United States healthcare landscape. The Center for Medicare and Medicaid (CMS) led transformation efforts in regulatory reform and coverage expansion across the U.S. population. Since 2010, care delivery systems have been shifting from episodic, decentralized and fee-for-service models to value-based population health models, like accountable care organizations (ACO). ACOs have been specifically primed for local response to improve the health of their communities. ACO research has traditionally focused on performance measures like mortality, readmissions, quality outcomes and savings. ACO organizational characteristics …

Anticholinergic Burden And Risk Of Cognitive Impairment In Older Adults, Syeda Hashimi

Theses and Dissertations

Studies reveal that 10-27% of older adults chronically use anticholinergic medications. Increased cumulative anticholinergic burden scores are associated with increased risks of dementia. The mechanisms by which anticholinergic drugs negatively impact cognition remain elusive. However, researchers speculate that the drug’s impairment of cholinergic neurons promotes neuroinflammation.

We hypothesize that drugs with anticholinergic properties will induce inflammation in the brain. MCP1 and IL 6 are chemokines that contribute to neuroinflammation. We investigated the influence of diphenhydramine (Benadryl) on the production of MCP1 and IL-6 in Normal Human Astrocytes and Paroxetine on the production of MCP1 in Normal Human Astrocytes and Normal …

Prediction Of The Vaginal Microbiome Using Urine Samples, Christopher R. Diachok

Theses and Dissertations

The vaginal microbiome is associated with women’s health, including but not limited to the pathogenesis of bacterial vaginosis, adverse pregnancy outcomes including preterm birth and sexually transmitted infections. However, there has been very limited research on the urinary microbiome and its relationship to the vaginal microbiome. We sought to predict the vaginal microbiome profile using clean catch urine samples from the same person. Here, paired vaginal and urine samples were collected and sequenced by 16S ribosomal RNA sequencing. Alpha and beta diversity analysis showed that there was no significant difference between the paired vaginal and urine microbiomes. In fact, a …

The Intersection Of Social Stress, Mental Well-Being, And Sexual Health Among Black Women In Emerging Adulthood, Brandi Galloway

Theses and Dissertations

With an estimated 37,000 new HIV infections each year, HIV continues to be a major public health concern. HIV affects some populations more than others. Young Black women, in particular, are disproportionately affected by HIV. While being a woman does not typically increase a person’s HIV risk, being Black and being a woman does.

Data indicate that individual-level factors do not fully address the differences in HIV and STIs between Black emerging adult women and their White counterparts. Thus, it is critical to better understand contextual factors such as social stress and mental-wellbeing which might better account for these disparities. …

Biopsychosocial Variables Associated With The Development Of Chronic Low Back Pain In Healthcare Workers, Jena Pauli

Theses and Dissertations

ABSTRACT

Purpose: Worldwide the incidence and prevalence of acute low back injury with pain (ALBIP) is increasing in healthcare workers (HCW). Approximately 27% of ALBIP result in chronic low back pain (CLBP). The primary aim of this study was to identify biopsychosocial factors that contribute to the development of CLBP. A secondary aim was to examine the predictive value of reliable and valid screening instruments to identify individuals at highest risk for CLBP.

Significance: Low back pain is the second most commonly reported pain condition in the United States, one of the leading causes of sick leave and …

Recovery From Visual Dysfunction Following Mild Traumatic Brain Injury Is Associated With Adaptive Reorganization Of Retinal Inputs To Lateral Geniculate Nucleus In The Mouse Model Utilizing Central Fluid Percussion Injury., Vishal C. Patel

Theses and Dissertations

Traumatic brain injury (TBI) is a leading cause of morbidity and mortality nationwide. Prevalence of mild TBI (mTBI) vastly outnumbers more severe forms however the associated morbidity has only recently gained public attention. Visual dysfunction is a significant component of mTBI associated morbidity with recovery of function linked with improvement in global outcomes. Examination of sensory and motor pathways in other brain injury paradigms support that recovery is largely dependent on adaptive plasticity of remaining connections. Current examinations of visual function recovery following mTBI is limited to identifying evidence for recovery and objective evidence for adaptive plasticity is limited. Therefore, …

“It’S Supposed To Be Super Easy And It’S Not”: Black And Latinx Student Experiences In The Doctor Of Physical Therapy Admissions Process, Melissa Yeung

Theses and Dissertations

Data provided by the Physical Therapy Central Application System (PTCAS) suggests that despite the large numbers of applicants to Doctor of Physical Therapy (DPT) programs on an annual basis, a gap remains between the number of White and Black and Latinx applicants who are offered admission to DPT programs. Efforts made by DPT programs to increase the diversity of their incoming cohorts include the use of holistic review processes and enrichment programs to recruit more diverse classes. However, research suggests that the undergraduate experiences of students of color have an impact on their aspirations to graduate and professional schools, and …

The Role Of Manganese In Streptococcus Sanguinis, Tanya M. Puccio

Theses and Dissertations

Streptococcus sanguinis is primarily associated with oral health as a commensal bacterium. As an opportunistic pathogen, S. sanguinis is capable of colonizing heart valve vegetations, leading to the disease infective endocarditis. Previous studies from our lab have identified the high-affinity manganese transporter SsaACB as important for endocarditis virulence. The impact that manganese depletion has on S. sanguinis had never been evaluated and a secondary manganese transporter has not been identified. Thus, we employed the use of a fermentor to control large-scale growth over time and depleted manganese in an ΔssaACB mutant using a metal chelator, EDTA. The changes in …

Changing Landscapes: Perspectives Of Young African American Women Of Population-Wide Testing For Hereditary Breast Cancer Mutations, Alesha Henderson

Theses and Dissertations

Young African American women continue to die from breast cancer at higher rates than White women. In an effort to promote breast cancer prevention, population-wide testing (PWT) for all women in the U.S. starting at age 30 is a potential future initiative that is garnering a lot of attention. However, African American women currently utilize genetic testing for hereditary breast cancer at lower rates than White women. Therefore, if young African American women are not prioritized in a future roll out of PWT, then existing breast cancer and genetic testing disparities will likely continue to widen. The purpose of this …