Medicine and Health Sciences Commons^™

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 …

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 …

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 …

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 …

Role Of Nurd In Acute Leukemia Cell Survival, Javeria Aijaz

Theses and Dissertations

Depletion of the ATPase component of the Nucleosome Remodeling and Deacetylase (NuRD) complex, CHD4, reduces acute myeloid leukemia (AML) cell survival. This study identified other NuRD components, as potential therapeutic targets for disrupting protein-protein interactions within NuRD. In addition to AML, we established that T-cell Acute Lymphoblastic Leukemia (T-ALL) cell lines responded similarly to CHD4 depletion.

Greater than 90% depletion of either MBD2 or MBD3 (the mutually exclusive two DNA binding NuRD paralogues) – was unremarkable, but complete depletion of MBD3 increased apoptosis and genotoxic sensitivity. Combined depletion of MBD-NuRD proteins augmented apoptosis observed with complete MBD3 depletion - indicating …

“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 …

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, …

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, …

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 …

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 …

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 …

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 …

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 …

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 …

Development Of A Torque-Based Device For The Quantification Of Arm Rigidity In Patients With Parkinson’S Disease, Georgina O. Miller

Theses and Dissertations

Parkinsonian rigidity is caused by the inability of the muscles to relax and extend properly, due to reduced dopamine levels and often begins on one side of the body before spreading contralaterally. The current standard for determining joint rigidity in a clinical setting is a test completed by the clinician based on the feel of the relaxed wrist and elbow joints as they are passively flexed and extended and a series of ordinal rating scales, the Movement Disorder Society’s – Unified Parkinson’s Disease Rating Scale (MDS-UPDRS), Hoehn and Yahr Scale (H&Y), and Parkinson’s Disease Questionnaire-39 (PDQ-39). These methods are used …

Development Of Dexamethsone Sodium Phosphate Loaded Nanoparticles For Treating Corneal Allograft Rejection, Vineet R. Kulkarni

Theses and Dissertations

Corneas are the most commonly transplanted tissue worldwide, with approximately 80,000 transplantations performed in the United States in 2018 alone. Corneal transplantation is used to restore the vision due to opaque corneas in various diseases such as fungal keratitis, keratoconus, Fuchs’s dystrophy, corneal ulceration, traumatic injury, abrasions or scarring, inflammation, and infection. Corneal transplant surgery could involve replacing the entire cornea (penetrating keratoplasty) or selective replacement of the corneal layers (e.g. Descemet’s membrane endothelial keratoplasty and deep anterior lamellar keratoplasty). Immunologic graft rejection is one of the main causes of graft failure in these corneal transplantations. The 2-year rejection rate …

A Qualitative Analysis Of Caregiver Goals For Urban Children With And Without Asthma, Megan M. Carlson

Theses and Dissertations

Pediatric asthma is a major public health concern that disproportionately affects children of color and youth living in low-income, urban areas. The implications for public health, child health, and family functioning necessitates our understanding and addressing experiences by families who are facing barriers within their socio-demographic context in addition to the stressors associated with managing pediatric asthma. The current study applied qualitative methods to interviews with caregivers of children with and without asthma in an effort to more deeply connect with caregivers’ experiences and yield richer information about the intersection of identities as Black caregivers living in an urban setting …