Characterizing Glycosaminoglycan And Glycosaminoglycan-Oligo Interactions With Cancer Stem Cells And Their Regulators, Rahaman Navaz Gangji

Theses and Dissertations

Tumor metastasis and recurrence account for more than 90% of cancer-associated deaths and are thought to occur due to a small subpopulation of neoplastic cells known as cancer stem cells (CSCs). Because CSCs are resistant to conventional chemotherapy, there is a critical need to develop CSC-targeting agents. Microenvironmental components, especially glycosaminoglycans (GAGs), play a key role in regulating CSC phenotype. GAGs such as heparan sulfate (HS) interact with hundreds of proteins and influence a variety of biological processes including tumor proliferation, angiogenesis, metastasis and stem cell biology.

Recently, the Desai and Patel laboratories have demonstrated that a hexasaccharide form of …

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 …

Psychometric Developments Of The Ace-Iq: Understanding The Trauma History Of Latine Immigrants, Jorli K. Swingen Dr.

Theses and Dissertations

Adverse childhood experiences (ACEs) have a profound effect on an individual’s physical and mental health. The World Health Organization has recently updated the ACE questionnaire so it could be used with international populations. The Adverse Childhood Experiences-International Questionnaire (ACE-IQ), has not been translated to Spanish or used with Latine immigrants.

This study translated the ACE-IQ into Spanish, evaluated the psychometric properties of the questionnaire, and collected data on 184 four adult English Language Learners in Chesterfield County, VA.

There is evidence of internal consistency for the ACE-IQ as a whole (α = .908) and within subscales. Three factors were identified …

Modulation Of Ferroportin In Oral Cancer, Ashley N. Hemingway

Theses and Dissertations

Iron plays a critical role in life sustaining functions for the cell. Dysregulation of these processes can be an issue with maintaining homeostatic conditions. Various cancer types have been observed to show malfunction in the maintenance of their iron homeostasis, in particular with the iron export protein—ferroportin. Ferroportin is the sole iron exporter known. Its structure and mechanism have not fully been elucidated yet, but its modulation has been associated with a poorer prognosis in cancers like breast, leukemia, prostrate, ovarian, colorectal, etc. Decreased iron exportation by ferroportin may lead to an increased labile iron pool allowing the cell to …

A Comparison Of Patient Testimonials On Youtube Of The Most Common Orthodontic Treatment Modalities: Braces, In-Office Aligners, And Direct-To-Consumer Aligners, Riley Hunsaker

Theses and Dissertations

Introduction: The objectives of this research was to investigate and compare the educational value of the most popular YouTube orthodontic patient testimonials between braces (B), in- office aligners (IOA), and direct-to-consumer aligners (DTCA), and to classify the emotional response of the viewers through a sentiment analysis of the video comments.

Methods: Three different phrases relevant to B, IOA, and DTCA were searched on YouTube. The 20 most popular patient testimonial videos that met the criteria for each group were selected, for a total of 60 videos. Using the YouTube API for each video, 13 video metrics were extracted, an information …

Design, Synthesis, And Biological Evaluation Of Mu Opioid Receptor Selective Antagonists Bearing Pyrazole And Imidazole Side Chains, Pornprom Klongkumnuankarn

Theses and Dissertations

Opioid Use Disorder (OUD) is one of the major national threats to human health and economic system. Since the opiate substances produce their pharmacological effects mainly at the Mu Opioid Receptor (MOR), the development of potent MOR selective antagonists is imperative. By application of the message-address concept, the novel selective MOR antagonist, NAP was synthesized in our group. The molecular modeling studies of NAP revealed that its MOR selectivity was determined by interactions between the C(6) side chain and the non-conserved residues of the receptor. To enrich our understanding of Structure-Activity Relationship (SAR) of the opioid ligands as well as …

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 …

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 …

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 …

A Cost-Effectiveness Analysis Of Early Literacy Growth In Public Pre-Kindergarten Programs, Bruce A. Fillman

Theses and Dissertations

Student early literacy readiness is predictive of later academic success and pre-k programs are a proven intervention to develop early literacy; however, the cost of pre-k programs differs greatly. These differences in cost are related to the opportunities and services included within each program. This study examined four pre-k programs offered within a large school system in Virginia to determine if there were differences in students’ early literacy growth by program attended and evaluated the ratio of cost to achievement of each pre-k program to determine their cost-effectiveness. To do this, two one-way analyses of variances (ANOVAs) were conducted to …

Smallest Worthwhile Effect Values For Pain And Function After A Total Knee Replacement, Nancy Wofford

Theses and Dissertations

ABSTRACT

SMALLEST WORTHWHILE EFFECT VALUES FOR PAIN AND FUNCTION AFTER A TOTAL KNEE REPLACEMENT

Nancy Henderson, PT

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

Virginia Commonwealth University, 2020

Dr. Dan Riddle, PT, PhD, Physical Therapy

Meaningful change is an important concept in healthcare as it allows providers to better understand the efficacy of an intervention. Three commonly used methods to assess meaningful change include the distribution-based, anchor-based, and benefit-harm trade-off methods. The benefit-harm trade-off method improves upon the limitations of the distribution-based and anchor-based methods. Unlike the …

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 …

Molecular And Behavioral Mechanisms Mediated Paclitaxel-Induced Changes In Affect-Like Behavior In Mice, Julia Meade

Theses and Dissertations

Paclitaxel and oxaliplatin are two chemotherapeutics that cause acute neurotoxicity and chemotherapy-induce peripheral neuropathy (CIPN) in 70-90% of cancer patients. Chemotherapy-induced sensory changes are correlated with depression and anxiety. We characterized the effects of these drugs on sensation and various mood-related behaviors in mice, to determine if changes in sensation are associated with depression-like behavior, to explore putative mechanisms of chemotherapy-induced depression-like behavior (Aim 1), and to develop a mouse model of chemotherapy-induced operant responding deficit (Aim 2). In Aim 1, we observed that a cumulative dose of 32 mg/kg paclitaxel induced mechanical hypersensitivity and transiently reduced preference for sucrose …

Interspecific Gene Flow Potentiates Adaptive Evolution In A Hybrid Zone Formed Between Pinus Strobiformis And Pinus Flexilis, Mitra Menon

Theses and Dissertations

Species range margins are often characterised by high degrees of habitat fragmentation resulting in low genetic diversity and higher gene flow from populations at the core of the species range. Interspecific gene flow from a closely related species with abutting range margins can increase standing genetic diversity and generate novel allelic combinations thereby alleviating limits to adaptive evolution in range margin populations. Hybridization driven interspecific gene flow has played a key role in the demographic history of several conifer due to their life history characteristics such as weak crossability barriers and long generation times. Nevertheless, demonstrating whether introgression is adaptive …

E-Liquid Exposure Causes Multiple Cardiovascular Defects In Xenopus Laevis Embryos, James E. Black Iii

Theses and Dissertations

Over the past several years vaping has become part of the cultural zeitgeist in the United States, with ECIG usage amongst those of reproductive age rising more and more. Due to a lack of regulation and research concerning their long term effects, public opinion trends toward the idea that they are somehow safer than their traditional counterparts. As cases of lung injury and ECIG related death are beginning to be reported more and more, it is clear that the misinformation about their safety is unfounded. Congenital heart defects (CHDs) are some of the most common birth defects currently in the …

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 …

Repeat Full Mouth Dental Rehabilitation Under General Anesthesia For Medicaid Eligible Healthy Children Who Are High Caries Risk, Lajoi E. Wiggins

Theses and Dissertations

Purpose: To evaluate the treatment of healthy children who are high caries risk and of low socioeconomic status and who require repeat full mouth dental rehabilitation (FMDR) under general anesthesia (GA).

Methods: A retrospective chart review was performed on healthy Medicaid eligible patients who were initially between 18 months - 6 years of age who underwent FMDR under GA in the OR more than once at the Virginia Commonwealth University (VCU) School of Dentistry, Department of Pediatric Dentistry from January 2008 to December 2018. Biographical information for each patient was gathered into a REDCap™ Survey. Statistical analysis, chi-squared test with …

Identifying And Addressing Barriers To Accessing Treatment For Substance Use Disorders Among Opioid-Misusing Individuals Following Implementation Of The Affordable Care Act, Mirinda A. Gormley

Theses and Dissertations

BACKGROUND: This project utilized opioid-misusing adults to investigate the association between type of opioid misuse and perceived readiness, financial, structural, and stigma-related barriers to accessing SUD treatment; identified classes of PSU and the association between patterns of PSU and perceived barriers, and evaluated effectiveness of an out-of-hospital opioid-treatment connection program.

METHODS: Respondents from 2015-2018 NSDUH included insured adults reporting past year opioid misuse. Multivariate logistic regression assessed relationship between type of opioid misuse and perceived barriers to SUD treatment. LCA identified patterns of PSU, and multivariate logistic regression assessed association between PSU classes and perceived barriers. EMS ePCRs for nonfatal …

Formulation And Validation Of Nanoparticle Controlled Delivery For Chemotherapeutic Drug Products, Shani L. Levit

Theses and Dissertations

Taxol, a formulation of paclitaxel (PTX), is one of the most widely used anticancer drugs, particularly for treating recurring ovarian carcinomas following surgery. Clinically, PTX is used in combination with other drugs such as lapatinib (LAP) to increase treatment efficacy. Delivering drug combinations with nanoparticles has the potential to improve chemotherapy outcomes. In this study, we use Flash NanoPrecipitation, a rapid, scalable process to encapsulate weakly hydrophobic drugs (logP in vitro. Encapsulating either PTX or LAP into nanoparticles increases drug potency. When PTX and LAP are co-loaded in the same nanoparticle, they have a synergistic effect that is greater than …

Exploring The Heteromeric Interface Of The 5-Ht2a-Mglu2 Receptor Complex, Mohamed Aarif Abdul Kareem

Theses and Dissertations

Schizophrenia is a serious mental disorder characteristic of several neurotransmitters including dopamine, serotonin, and glutamate being in imbalance. Early therapies focused solely on dopamine antagonism and second-generation antipsychotics focused on the dopamine and serotonin systems and their respective G protein coupled receptor (GPCR) proteins. Although debate for dimerization of certain classes of GPCR exist, the establishment of an mGlu2-5-HT_2A heterocomplex, which is implicated in schizophrenia is of interest. Previous studies have used a mutation-based approach to identify transmembrane domain 4 (TM4) as the domain responsible in mGlu2 for mediating heteromerization before narrowing down the individual amino acids responsible for …

Pharmacology Of Fentanyl-Related Substances In Mice Reveals Potential Therapeutics With Improved Protective Indices, Neil B. Varshneya

Theses and Dissertations

Fentanyl-related substances constitute a class of compounds that were originally developed in the latter half of the 20th century as combination analgesic-anesthetic agents. Today, many of these compounds have emerged in the recreational drug marketplace as adulterants to heroin, counterfeit prescription pills, and even as standalone products designed to circumvent drug control laws. The objective of this dissertation was to identify the structural determinants of fentanyl analogs that could affect the potency and efficacy for eliciting their therapeutic and toxic effects to identify candidates of potential therapeutic interest. To accomplish this objective, thirty-eight fentanyl-related substances, in addition to the MOR …

Monumentalizing Rituals Of The Palestinian Diaspora, Reema Abu Hassan

Theses and Dissertations

Displaced Palestinians have historically sought to preserve their Palestinian memories and identities in order to remain connected to their lost homeland. Despite the importance of memory for them, and their history of suffering and exile, there have not been any significant monuments designed to preserve their collective memory.

This thesis considers the adaptation of a traditional monument by redesigning it to the specificity of the Palestinian diaspora. In doing so it proposes the monumentalizing of four Palestinian rituals to add significance, meaning and permanence to them. The four rituals are making maamoul, applying orange and mashmoom perfume oil to …

A Comparison In Pediatric Dental Website Design From A Guardian And Pediatric Dentists’ Perspective., David M. Voth

Theses and Dissertations

Purpose: This project aims to determine which aspects of pediatric dental practice websites are preferable to the guardians of pediatric dental patients and which of these aspects are currently available to guardians on the websites of pediatric dental practices across the United States. The comparison will reveal if practice websites are meeting the needs of the guardians of pediatric dental patients. Our hope is to provide meaningful guidance to pediatric dentists designing new practice websites and to provide the guardians of pediatric dental patients with an appealing online experience during their use of the aforementioned websites. Methods: A survey with …

Investigating The Role Of Oncogene C-Terminal Binding Protein (Ctbp) In Pancreatic Ductal Adenocarcinoma, Kranthi Kumar Chougoni

Theses and Dissertations

The transcriptional coregulator CtBP2 has been implicated as an oncogene in colon, prostate, breast and ovarian cancers. Previously, we reported overexpression of CtBP2 in human PDAC specimens. However, its exact role in PDAC is still unclear. In the current study, we attempt to delineate the oncogenic role CtBP2 in PDAC growth and metastasis. Using an orthotopic syngeneic pancreatic tumor mouse model (CKP), we found that deletion of Ctbp2 decreases PDAC tumor growth, proliferation, metastasis, EMT and significantly prolongs survival. Further, we identified significant downregulation of Erbb3 mRNA levels upon deletion of Ctbp2 in CKP PDAC cells As ErbB3 signaling was …

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 …

Internalizing Data Collection: Personal Analytics As An Investigation Of The Self, Neal R. Swisher

Theses and Dissertations

Personal analytics, aka self-tracking, is the practice of using a digital device to track aspects of behavior, such as exercise habits, heart rate, sleep patterns, location, diet, and a host of other data points. This dissertation is an exploration of “self” in self-tracking, informed by theories of subjectivity, autonomy, power and knowledge. As a technological intervention, self-tracking devices change how we experience our own body and behavior. They also serve as methods to digitize human behavior. This data is combined with other data and processed using computational methods. Self-tracking devices are both personal and bureaucratic. They are devices used for …

A Theoretically-Based Mixed Methods Approach To Examining Mental Health Disorders And Help-Seeking Behaviors Among University-Enrolled African American Men, Kofoworola D.A. Williams

Theses and Dissertations

Recent studies show that African American men in college are disproportionately experiencing high levels of psychological distress, increasing their risk of developing mental health symptoms associated with depression and anxiety. Despite being at higher risk for developing mental health symptoms, university-enrolled, African American men are not seeking help even when experiencing high levels of stress and anxiety, impacting their academic performance. The evidence base describing mental health symptom prevalence and evidence-based prevention strategies among university-enrolled, African American men is limited. To that end, this dissertation work utilized a concurrent, mixed methods approach, theoretically-based in the Social Ecological Model (SEM), to …

Examining Body Mass Index And Sepsis Mortality At One Year After Sepsis, Jamie D. Robinson

Theses and Dissertations

Introduction: Sepsis is a serious and life-threatening syndrome affecting 1.7 million Americans annually and resulting in approximately 270,000 deaths. An “obesity paradox” where obese individuals have lower sepsis mortality than their non-obese counterparts has been described. The problem is that the longevity of the effect is unknown, and few studies have examined the obesity paradox after 1-2 months post-diagnosis.

Methods: This retrospective cohort study examined clinical, demographic, and biomarker variables thought to affect sepsis mortality at three-time points: 30 days, 180 days, and at one year post-sepsis diagnosis in order to shed light on specific factors that might define …

Kavana: Photography, Jewish Storytelling, And Memory, Hannah Altman

Theses and Dissertations

Jewish thought suggests that the memory of an action is as primary as the action itself. This is to say that when my hand is wounded, I remember other hands. I trace ache back to other aches - when my mother grabbed my wrist pulling me across the intersection, when my great-grandmother’s fingers went numb on the ship headed towards Cuba fleeing the Nazis, when Miriam’s palms enduringly poured water for the Hebrews throughout their desert journey - this is how the Jew is able to fathom an ache. Because no physical space is a given for the Jewish diaspora, …

Hopeless Heartland: Space And Labor In Virginia, Katrina Hamilton

Theses and Dissertations

In the US, labor market conditions vary by demographics and space. Though space has been shown to be highly related to labor force outcomes, lower-level analyses are under-utilized as statistical workforce analyses tend to rely on national or state-level data. This study addresses variability in labor markets by taking a spatial approach, using cluster analysis and logistic regression to explore variations in labor market variables across census tracts in Virginia. Cluster analysis reveals several hot and cold spots of key labor market indicators: rates of marriage, poverty, educational attainment, and income. In many cases, poor social conditions, such as low …