Medicine and Health Sciences Commons^™

Genomic Instability In Severe Congenital Neutropenia, A Leukemia Predisposition Syndrome, Adya Sapra

Theses and Dissertations

Severe congenital neutropenia (SCN) is a rare blood disorder characterized by abnormally low levels of circulating neutrophils. Mutations in multiple genes like neutrophil elastase gene (ELANE) and granulocyte colony stimulating factor receptor (CSF3R) may cause SCN. The treatment of choice for SCN is the administration of granulocyte-colony stimulating factor (G-CSF) which elevates the neutrophil count and hence improves the survival and quality of life. Long term survivorship on G-CSF is however linked to development of MDS (myelodysplastic syndrome)/AML (acute myeloid leukemia). About 70% of MDS/AML patients acquire nonsense mutations affecting the cytoplasmic domain of CSF3R. …

Predicting Arterial Oxygen Desaturation Events Via Patient Journal And Pulse Oximetry Data In Postoperative Ambulatory Surgery Patients, Charles R. Elam Iv

Theses and Dissertations

Associations between patient and procedural factors on the nature and quality of the immediate in-home recovery from anesthesia following ambulatory orthopedic surgery are unknown. Further, there is a paucity of outcomes research quantitatively categorizing in-home

patient recovery and safety following discharge from same-day orthopedic procedures. Tools are available, however, to shed light on outcomes in this population, and integration of such available measures is critical.

Ambulatory orthopedic surgery is a burgeoning specialty, with growth expected over the foreseeable future. The expected increased patient caseload subsequent to implementation of the Affordable Care Act and aging Baby Boom generation suggests greater morbidity …

Alternative Splicing Of Cytoplasmic Polyadenylation Element Binding Protein 2 Is Modulated Via Serine Arginine Splicing Factor 3 In Cancer Metastasis, James T. Deligio, James Thomas Deligio

Theses and Dissertations

Our laboratory delineated a role for alternative pre-mRNA splicing (AS) in triple negative breast cancer (TNBC). We found the translational regulator cytosolic polyadenylation element binding protein 2 (CPEB2) which has two isoforms, CPEB2A and CPEB2B, is alternatively spliced during acquisition of anoikis resistance (AnR) and metastasis. The splicing event which determines the CPEB2 isoform is via inclusion/ exclusion of exon four in the mature mRNA transcript. The loss of CPEB2A with a concomitant increase in CPEB2B is required for TNBC cells to metastasize in vivo. We examined RNAseq profiles of TNBC cells which had CPEB2 isoforms specifically downregulated to …

Influence Of Muscle Strength On Mobility In Critically Ill Adult Patients On Mechanical Ventilation, Audrey R. Roberson

Theses and Dissertations

Patients in the intensive care unit (ICU) setting are prone to develop muscle weakness and the causes are multi-factorial. Muscle strength in adult, critically ill patients on mechanical ventilation decreases with immobility. The influence of muscle strength on different muscle groups and its influence on progressive mobility in the adult, critically ill patient on mechanical ventilation has not been examined. Identifying muscle strength in this patient population can benefit overall muscle health and minimize muscle deconditioning through a progressive mobility plan. The objective of this dissertation was to describe muscle strength in different muscle groups and to describe the influence …

Age-Dependent Changes In Oxygen Supply And Demand Of Rat Spinotrapezius Muscle, Sami C. Dodhy

Theses and Dissertations

Because of the aerobic nature of cellular metabolism in mammalian organisms, a continuous supply of oxygen is necessary to maintain normal physiological function. As organisms age, their metabolic rates generally decline and there are accompanying alterations in the structure and function of the microcirculation, as this part of the cardiovascular system is especially important for oxygen exchange. The overall Oxygen Transport System can be considered as being composed of two complementary components: one for Oxygen Demand and one for Oxygen Supply. The purpose of the current work is to describe the age-dependent changes in both oxygen demand and oxygen supply …

Evaluating And Reducing The Effects Of Misclassification In A Sequential Multiple Assignment Randomized Trial (Smart), Jun He

Theses and Dissertations

SMART designs tailor individual treatment by re-randomizing patients to subsequent therapies based on their response to initial treatment. However, the classification of patients being responders/non-responders could be inaccurate and thus lead to inappropriate treatment assignment. In a two-step SMART design, by assuming equal randomization, and equal variances of misclassified patients and correctly classified patients, we evaluated misclassification effects on mean, variance, and type I error/ power of single sequential treatment outcome (SST), dynamic treatment outcome (DTRs), and overall outcome. The results showed that misclassification could introduce bias to estimates of treatment effect in all types of outcome. Though the magnitude …

The Role Of Adam10 And Adam17 In Humoral And Type 2 Immunity, Joseph C. Lownik

Theses and Dissertations

The proper regulation of inducible costimulator (ICOS) and its ligand (ICOSL) have been shown to be essential for maintaining immune homeostasis. Loss of either protein results in defective humoral immunity, and overexpression of ICOS results in aberrant antibody production resembling lupus. How ICOSL is regulated in response to ICOS interaction is still unclear. We demonstrate that ADAM10 is the primary physiological sheddase of ICOSL in both mouse and human. Using an in vivo system in which ADAM10 is deleted only on B cells (ADAM10^B-/-), elevated levels of ICOSL were seen. This increase is also seen when ADAM10 is …

Effects Of Hiv-1 Tat And Drugs Of Abuse On Antiretroviral Penetration Inside Different Cns Cell Types, Sulay H. Patel

Theses and Dissertations

Human immunodeficiency (HIV) infection can result in neurocognitive deficits in about one-half of infected individuals. Despite excellent systemic effectiveness, restricted antiretroviral penetration across the blood-brain barrier (BBB) is a major limitation in fighting HIV infection within the central nervous system (CNS). Drug abuse exacerbates cognitive impairment and pathologic CNS changes in HIV-infected individuals. This work investigates the effects of the HIV-1 protein, Tat, and drugs of abuse on factors affecting drug penetration into the brain.

Firstly, an in vitro model of the blood-brain barrier was built to study effects of HIV-1 Tat and methamphetamine (Meth) on integrity and function of …

Relationship Between Patient-Health Coach Interactions And Changes In Markers Of Glucose Homeostasis, Jason P. Nagy

Theses and Dissertations

Diabetes and insulin resistance are on the rise in the United States. Early detection and deployment of therapies has allowed for the reversal of pancreatic beta cell damage. Unfortunately, not all providers can offer the support to facilitating the required life style modifications. The introduction of clinical health consultants (CHC) as supplemental care has improved patient health for a variety of chronic diseases. Missing in the literature are studies investigating the correlation between the number of CHC interactions and improvement in biomarkers.

The study utilized a non-experimental, retrospective study design to evaluate the relationship between the use between the use …

Family Planning And Hiv Interventions Among Women In Low-Income Settings, Steven P. Masiano

Theses and Dissertations

This dissertation examines the effectiveness of interventions related to family planning and the uptake of HIV-related preventive services among women in low-income settings. Women in low-income settings and living with HIV face many barriers to care, including limited access to services for family planning and HIV-related preventive care. At the same time, national, regional, and global efforts are looking for interventions to help control rapid population growth, create an HIV-free generation, and provide adequate preventive care for those living with HIV. This dissertation cuts across these issues and can help to inform debate and policies to address these issues.

This …

Drug Delivery With Light, Patrick S. Dupart

Theses and Dissertations

Cancer is responsible for about 25% of deaths in developed countries and for 15% of all deaths worldwide. Cancer is a devastating disease and while there have been great advances in the development of anticancer drugs, off-target toxicity is a major limitation with conventional cancer chemotherapy. The consequence of this form of treatment results in the killing of healthy and rapidly-growing non-cancerous cells including cells in the bone marrow; hair follicles; and cells in the mouth, digestive tract, and reproductive system. In addition to these general effects, certain anticancer drugs can have other associated toxicities. For instance, the anticancer drug …

"To Conceive With Child Is The Earnest Desire If Not Of All, Yet Of Most Women": The Advancement Of Prenatal Care And Childbirth In Early Modern England: 1500-1770, Victoria E.C. Glover

Theses and Dissertations

This thesis analyzes medical manuals published in England between 1500 and 1770 to trace developing medical understandings and prescriptive approaches to conception, pregnancy, and childbirth. While there have been plenty of books written regarding social and religious changes in the reproductive process during the early modern era, there is a dearth of scholarly work focusing on the medical changes which took place in obstetrics over this period. Early modern England was a time of great change in the field of obstetrics as physicians incorporated newly-discovered knowledge about the male and female body, new fields and tools, and new or revived …

Reducing Sepsis Mortality: A Cloud-Based Alert Approach, Janet A. Zink

Theses and Dissertations

The aim of this study is to examine the impact of a cloud-based CDS alerting system for SIRS, a precursor to sepsis, and sepsis itself, on adult patient and process outcomes at VCU Health System. The two main hypotheses are: 1) the implementation of cloud-based SIRS and sepsis alerts will lead to lower sepsis-related mortality and lower average length of stay, and 2) the implementation of cloud-based SIRS and sepsis alerts will lead to more frequent ordering of the Sepsis PowerPlan and more recording of sepsis diagnoses. To measure these outcomes, a pre-post study was conducted. A pre-implementation group diagnosed …

The Impact Of Mother–Father Relationship, Social Support And Neighborhood Context On Preterm Birth, Timothy O. Ihongbe

Theses and Dissertations

Background: Preterm birth is a major public health concern in the US. Previous studies have suggested that quality of the mother-father relationship, social support, and neighborhood violence may be associated with preterm birth; however, findings are equivocal.

Objectives: The main objectives of this dissertation were: 1) to determine the modifying effect of perceived residential environment on the association between quality of mother–father relationship and preterm birth in a sample of African-American women, 2) to examine whether the receipt of social support modifies the association between neighborhood violence exposure and preterm birth in a nationally representative sample of US women, and …

Effects Of A 2-Week Exercise Intervention On Heart Rate Variability In Individuals With Low And High Anxiety Sensitivity, Hannah M. Kotarski

Theses and Dissertations

Anxiety Sensitivity (AS), the belief that anxiety-related sensations may have harmful implications, can alter autonomic nervous system (ANS) function. Exercise has previously been shown to reduce AS; however, the effects of an exercise intervention on heart rate variability (HRV), a measure of ANS function, has not been evaluated in individuals with high AS. This study sought to 1) compare resting HRV in individuals with either low (LAS) or high AS (HAS) and 2) evaluate the effects of a 2-week exercise intervention on HRV and AS. Using the Anxiety Sensitivity Index (ASI-3), participants were identified as LAS (n=9; ASI-3=5.89±1.39) or HAS …

The Effect Of Biologic Materials And Oral Steroids On Radiographic And Clinical Outcomes Of Horizontal Alveolar Ridge Augmentation., Amy Reichert

Theses and Dissertations

The purpose of this study was to investigate if the addition of biologic materials and/or oral steroids would affect horizontal bone gain, or the bone density of the grafted bone in horizontal alveolar ridge augmentations. A retrospective chart review was completed to assess the clinical and radiographic outcomes of 53 ridge augmentation patients. An average bone gain of 3.6mm of width was found in our study based on radiographic analysis. There were no statistically significant differences found in the linear bone gain with the addition of biologic materials and steroids. A marginally statistically significant difference was found in the bone …

A Stakeholder Examination Of Gestational Weight Gain Guidelines, Melissa Kwitowski

Theses and Dissertations

Obesity is a significant health concern for women of childbearing age. More than 40% of women have a Body Mass Index (BMI) in the overweight or obese ranges at the time they conceive, posing significant health risks for both mother and child. Excessive weight gain during pregnancy is common and associated with numerous deleterious complications. The Institute of Medicine published gestational weight gain (GWG) guidelines based on prepregnancy BMI. However, more than 50% of women gain in excess of these recommendations. Further, many women report receiving minimal guidance from their healthcare providers regarding weight gain, nutrition, and physical activity during …

Estimating The Respiratory Lung Motion Model Using Tensor Decomposition On Displacement Vector Field, Kingston Kang

Theses and Dissertations

Modern big data often emerge as tensors. Standard statistical methods are inadequate to deal with datasets of large volume, high dimensionality, and complex structure. Therefore, it is important to develop algorithms such as low-rank tensor decomposition for data compression, dimensionality reduction, and approximation.

With the advancement in technology, high-dimensional images are becoming ubiquitous in the medical field. In lung radiation therapy, the respiratory motion of the lung introduces variabilities during treatment as the tumor inside the lung is moving, which brings challenges to the precise delivery of radiation to the tumor. Several approaches to quantifying this uncertainty propose using a …

Glycosaminoglycan Lyases In The Preparation Of Oligosaccharides, Alhumaidi B. Alabbas

Theses and Dissertations

Glycosaminoglycans are heterogeneous polysaccharides that mediate important biological functions. There has been considerable interest in deciphering the precise GAG sequences that are responsible for protein interactions. In fact, several GAG oligosaccharides have been discovered to date as targeting proteins with higher level of specificity. Yet, it has been difficult to develop GAG oligosaccharides as drugs. One of the key reasons for this state of art is that GAG synthesis is extremely challenging and is highly structure-specific. Thus, much of the biology and pharmacology of GAG remains unknown and unexploited to date.

An alternative approach is to prepare GAG oligosaccharides using …

Counterregulatory Effects Of Ptx3 On Inflammation And Cellular Aging, Aaron L. Slusher

Theses and Dissertations

Pentraxin 3 (PTX3) is a vital regulator of innate immune function that has been shown to counterregulate pro-inflammatory signaling and protect against the development of cardiovascular disease (CVD). Less is known about how PTX3 may mitigate against CVD risk by regulating the pro-inflammatory response at the cellular level. Therefore, this dissertation details four manuscripts which aimed to examine the capacity of PTX3 to regulate the innate immune response of peripheral blood mononuclear cells (PBMCs) isolated from healthy adults. Manuscript 1 examined the capacity of PTX3 to alter the inflammatory milieu following in vitro stimulation of isolated PBMCs with the pro-inflammatory …

Gastrointestinal Microbiota Modulate Antinociceptive Tolerance Development In Mice With Chronic Morphine Exposure, Ryan A. Mischel

Theses and Dissertations

In October 2017, the United States government declared a state of public health emergency in response to the burgeoning prescription opioid epidemic. Opioid analgesics are the gold standard of therapy for moderate to severe pain, but their clinical utility is greatly limited by analgesic tolerance – a primary driver of diminished pain control and opioid dose escalations. Integral in this process are primary afferent sensory neurons in dorsal root ganglia (DRG), the first-order components of nociceptive sensation. With surmounting evidence that morphine and other narcotics can alter gut microbial composition and promote bacterial translocation to other tissues, a question arises …

The Periodontal Specialty: A Survey Regarding Our Future, John H. White

Theses and Dissertations

Purpose: To determine the characteristics influencing periodontal practices in Virginia and report on the anticipated changes in practice.

Methods: A REDCap survey was emailed to Virginia based American Academy of Periodontology (AAP) members assessing personal and practice demographics, trends in dental treatment and practice models, and how periodontists will adjust to account for these trends.

Results: The response rate was 31% (n=46). Respondents report greater referrals from more experienced general practitioners (GPs). Student debt was associated with age. Respondents ranked biologic advances, treatment of peri-implantitis, digital dentistry, development of corporate and group practice models, and GPs incorporating more periodontal …

A Comparison Of Quality Indicators Between Medicare Accountable Care Organizations And Health Maintenance Organizations Using Publicly Available Data, William W. Campbell Iii

Theses and Dissertations

The purpose of this study is to explore differences in quality between Medicare Accountable Care Organizations (ACO) and Health Maintenance Organizations (HMO). Three outcomes measures reported by these plans use different methodologies but possess enough alignment to permit comparison: percent of diabetic patients with last HbA1c > 9.0%, colon cancer screening rate and ER visits per 1,000. These outcomes are the dependent variables (DV). A secondary purpose is to explore differences in quality based on the size of the beneficiary population served, using the same measures.

As the Medicare program faces threats to its solvency in coming decades, with 10,000 baby …

A Comparison Of The Antimicrobial Efficacy Of Silver Diamine Fluoride And Silver Nitrate: An In Vitro Study, Nicholas L. Luke

Theses and Dissertations

A COMPARISON OF THE ANTIMICROBIAL EFFICACY OF SILVER DIAMINE FLUORIDE AND SILVER NITRATE: AN IN VITRO STUDY

By: Nicholas L Luke, D.D.S.

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

Virginia Commonwealth University, May 2018

Thesis Advisor: William O. Dahlke Jr., D.M.D.

Pediatric Dentistry, Department Chair

Purpose: To determine the antimicrobial efficacy of SDF and SN/NaF.

Methods: Three bacterial species were combined to create an in vitro biofilm. Treatment was completed with SN, SN/NaF, SDF, SDF½ or untreated (control).

Results: The untreated group demonstrated significantly higher …

Prevalence And Factors Of Sibling-Recurrent Dental Treatment Under General Anesthesia, Brandy N. Edmonds

Theses and Dissertations

Objective/Aims: Assess the prevalence of sibling recurrent dental general anesthesia (DGA) at VCU Pediatric Dentistry. Assess factors that contribute to sibling recurrent dental general anesthesia. Methods: The guardian of patients with siblings were provided a questionnaire to assess the prevalence and factors associated with recurrent DGA. Results: A total of 40 families with a child presenting for GA and at least one sibling were included in the study. Of these, 45% had sibling-recurrent GA treatment (20% in one sibling; 25% in 2 or more siblings). Additionally, 13% of the children currently presenting for GA had already been treated under GA, …

Assessment Of Pediatric-Focused Brief Motivational Interviewing Training Of Dental Students And Pediatric Dental Residents, Victoria M. Onesty

Theses and Dissertations

Purpose: To assess dental students and pediatric dental residents’ knowledge and attitudes towards motivational interviewing and evaluate the efficacy of a pediatric-focused brief motivational interviewing training program.

Methods: A total of 66 participants were enrolled; 35% were third year dental students, 46% were fourth year dental students and 18% were pediatric dental residents. Participants completed three questionnaires: the first before the training, the second immediately after the training and the third approximately 3.5 months after the training.

Results: A significant increase in correct responses was found for 4 of the 5 questions assessing participants’ knowledge. Participants were satisfied with the …

Metabotropic Glutamate Receptor 2 Activation: Computational Predictions And Experimental Validation, Amr Ellaithy

Theses and Dissertations

G protein-coupled receptors (GPCRs) are the largest family of signaling proteins in animals and represent the largest family of druggable targets in the human genome. Therefore, it is of no surprise that the molecular mechanisms of GPCR activation and signal transduction have attracted close attention for the past few decades. Several stabilizing interactions within the GPCR transmembrane (TM) domain helices regulate receptor activation. An example is a salt bridge between 2 highly conserved amino acids at the bottom of TM3 and TM6 that has been characterized for a large number of GPCRs. Through structural modeling and molecular dynamics (MD) simulations, …

The Influence Of Clinically Meaningful Factors On The Performance Of The Recommended Annual Diabetic Foot Screening, Trisha A. Sando

Theses and Dissertations

Background: Diabetic foot ulcers are the result of multiple complications from hyperglycemia and lead to poor quality of life and high healthcare costs. The annual diabetes foot screening exam (ADFSE) and prevention interventions can reduce DFUs up to 75%. In 2015, 71% of the US population received the ADFSE.

Objectives: The main objectives of this dissertation were: 1) to determine the association between adherence to diabetes self-management behaviors and the ADFSE, 2) to determine the association between concordant and discordant comorbidities and the ADFSE and 3) to determine the association between the performance of diabetes preventive care processes, number of …

Queer Health Equity And Cervical Cancer: Identifying Social Determinants Of Papanicolaou Test Uptake In A Sample Of Sexual Minority Women And Gender Nonbinary Individuals, Ariella R. Tabaac

Theses and Dissertations

Sexual minority women (SMW) demonstrate lower rates of cervical cancer screening than heterosexual women. This is concerning as lesbian and bisexual women tend to engage in higher rates of substance-related cancer risk behaviors, unprotected sex, and tend to have higher body mass indices, all of which are risk factors for cancer development. Another major risk factor, screening avoidance, places SMW at increased risk for the development of high grade cervical lesions in the absence of early detection practices, which is likely to impact overall cervical cancer morbidity in this population. The aim of the present study was to utilize the …

Comparison Of Hiring Strategies Of Orthodontic Private Practitioners, Steven C. Petritz

Theses and Dissertations

COMPARISON OF HIRING STRATEGIES OF ORTHODONTIC PRIVATE PRACTITIONERS

By Steven C. Petritz, D.D.S.

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

Virginia Commonwealth University, 2018

Thesis Director: Bhavna Shroff, D.D.S., M.Dent.Sc., M.P.A.

Virginia Commonwealth University Department of Orthodontics Program Director

Purpose: Evaluate factors that influence hiring outcomes of clinical and non-clinical staff in orthodontic private practices.

Methods: Orthodontists (n=1968) were surveyed regarding their hiring methods and outcomes. Responses were summarized using descriptive statistics. Chi-square tests were used to compare between hiring strategies and outcomes. …