Medicine and Health Sciences Commons^™

Development Of An R Script For Simple Lipidomic And Metabolomic Data Analysis, Suad Alshammari, Joshua M. Morriss, Daniel Contaifer, Dayanjan S. Wijesinghe, Monther Alsultan

Graduate Research Posters

Background: Metabolomic and lipidomic studies generate vast quantities of data that are often analysed in a closed software environment with little to no access to the underlying algorithms. As a result, data processed via different software pipelines yield different results thus leading to a widespread problem of low reproducibility within these fields. To address this problem, we are developing LipidAnalyst; an R based lipidomics software pipeline. As a part of this project, we are creating a simple statistical analysis and graphing module in R to generate accurate, reproducible, high-resolution figures.

Methods: R scripts were developed under version 3.5.3 with the …

A Pre-Transplant Blood-Based Lipid Signature For Prediction Of Antibody-Mediated Rejection In Kidney Transplant Patients, Monther Al Sultan, Daniel Contaifer Jr., Joshua Morriss, Suad Alshammari, Jeffrey Stern, Sindhura Bobba, Pamela Kimball, Anne King, Dhiren Kumar, Marlon Levy, Gaurav Gupta, Dayanjan Wijesinghe

Graduate Research Posters

Purpose. The aim of this study is to demonstrate the potential of the pre-transplant lipidome to predict post-transplant antibody-mediated rejection (AMR) in kidney transplant patients.

Methods. Patients were selected from a prospective observational cohort of a single-center adult kidney transplant center in the United States. The study included 16 kidney transplant patients who develop AMR within 2 years post-transplant and 29 stable control (SC) kidney transplant patients who did not develop AMR at any time within the post-transplant follow up. Selection of group differences on the day of transplant was determined by t-test analysis. Stepwise forward method was used to …

Molecular Predictors Of Anakinra Treatment Success In Heart Failure Patients With Reduced Ejection Fraction, Joshua Morriss, Daniel Contaifer Jr, Leo F. Buckley, George Wohlford, Monther Alsultan, Suad Alshammari, Asanga D. Ranasinghe, Salvatore Carbone, Justin M. Canada, Cory Trankle, Elvin T. Price, Antonio Abbate, Benjamin W. Van Tassell, Dayanjan S. Wijesinghe

Graduate Research Posters

Background. Kineret (Anakinra) is an interleukin-1 antagonist that is under investigation for its novel clinical application treating patients that have heart failure with reduced (<50%) ejection fraction (HFrEF). A prior study from our group indicated that Anakinra may restore heart function by addressing dysregulations in HFrEF metabolic pathways. Herein, we attempt to elicit Anakinra’s effects on both metabolome and lipidome.

Methods. Lipids and metabolites that had previously been quantified by mass spectrometry (MS) from patients (n=49) who had ≥2 mg/L of high-sensitivity C-reactive protein (hs-CRP) were mTIC normalized and transformed. We conducted a stepwise Linear Discriminant Analysis (r- LDA) to test Anakinra (2 and 12 weeks) vs placebo for separation from combined baseline. Metabolic pathway analysis was performed with Fisher’s exact test algorithm for detection of over-represented and enriched analytes. Univariate analysis (one tailed t-test …

Guadecitabine, In Combination With Cyclophosphamide, Promotes Anti- Cancer Immunity In Balb/C Mice Bearing 4t1 Mouse Mammary Carcinoma, Carmen Camarena, Timothy M. Smith, Rebecca K. Martin Phd, Harry D. Bear Md

Graduate Research Posters

Background: The extremely high mortality rate of patients diagnosed with triple negative breast cancer makes it one of the deadliest forms of cancer. Due to the heterogenous nature of tumors, complete clearance is not achieved and clonal selection occurs resulting in tumor cells evading the immune system. I aim to design a therapeutic intervention that is able to elicit an effective immune response against the tumor and instill immunological memory to eradicate primary and metastatic lesions. I hypothesize that the combination of Guad and Cyp will synergize and promote anticancer immunity via increased expression of neo-tumor antigens and depletion of …

Determining The Impact Of Increased Physical Activity On Improving Sleep Quality In Young Adults, Ashley Darling, Alex Chiu, Eric Henderson, Aaron Autler, Jennifer Weggen, Kevin Decker, Ryan Garten

Graduate Research Posters

Determining the Impact of Increased Physical Activity on Improving Sleep Quality in Young Adults

Disturbed sleep, defined as any alteration to normal sleep patterns, has been linked to poor cardiovascular health and an increase in cardiovascular disease (CVD) risk. These negative sleep patterns are highly prevalent with 35% to 41% of individuals in the United States reported some form of disturbed sleep. Although high amounts of physical activity (PA) are often associated with high sleep quality, little is known about PA’s effectiveness to improve different aspects of sleep (e.g. duration vs quality) and the mechanisms to which it can improve …

Richmond City Health District (Rchd), Bon Secours Richmond City Hospital (Rch), And Virginia Commonwealth Universities (Vcu) Department Of Health Behavior Policy (Hbp): Partnering With Community Health Workers (Chw) To Improve Community Health Outcomes And Reduce Emergency Department (Ed) Use, Anita M. Kumar, Mph, Stephanie Toney, Rn Bsn, Tamera Langhorne, Mba Chw, Bassan Dahman, Ph.D.

Graduate Research Posters

Background: Frequent ED users (5%) are sicker, poorer, not satisfied with the health system and cost 20% of total ED charges.

Objective: A pilot study of feasibility of partnering with CHW to improve health knowledge and outcomes and reduce ED use in low income community.

Methods: RCH ED utilizers were randomized to intervention and control groups. CHW contacted intervention group within 10 days of ED visit, surveyed about access to care, healthy living, and knowledge about chronic disease, and offered education, referrals to insurance and social and economic support. ED utilization and cost were recorded for all patients for 6 …

The Clinical Inquiry Process Diagram, Roy E. Brown

VCU Libraries Faculty and Staff Publications

No abstract provided.

Bridging The Digital Divide: A Risk-Based “Telehealth Needs” Scoring Model For Patient Outcome Prediction, Cindy Ann Crump

Theses and Dissertations

The purpose of the research was to develop a predictive model of the effect of patient characteristics on outcomes and resource utilization in telehealth interventions for chronic disease management. Clinical studies have shown high variability in telehealth across settings and populations. The central hypothesis of this study was that patient characteristics, including disease type, illness severity, demographic information, and socio-technical preferences play a role in determining telehealth intervention outcomes. A non-experimental, retrospective study evaluated the feasibility of creating a Telehealth Needs score using Medicare and Medicaid claims data from 2016 to 2017. Claims were summarized into de-identified cases to train …

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 …