Digital Commons Network^™

Parental Experience With Whole Exome Sequencing Reanalysis And Its Impact On The Diagnostic Odyssey, Nicole D. Lucas

Theses and Dissertations

Advances in genomic technology and an increase in the number of gene-disease associations have helped reduce the number of individuals living without a diagnosis. Whole exome sequencing (WES) analyzes the entire human exome in an attempt to determine if there is a molecular etiology for individuals who remain undiagnosed after other clinical or molecular investigations. Still, WES leaves most individuals undiagnosed, resulting in feelings of disappointment and uncertainty. Individuals who remain undiagnosed after WES can subsequently undergo WES reanalysis later due to improvements in bioinformatics, software updates, and an increase in known genedisease associations. This is the first study, to …

Enhancements In Alginate Microencapsulation Technology & Impacts On Cell Therapy Development, Marwa Belhaj

Theses and Dissertations

Biodegradable alginate microcapsules (MC) are recently becoming widely used in the biomedical field, and have shown effectiveness as a drug delivery system. Alginate has been used in microencapsulation due to its simple gelling process, biodegradability, excellent biocompatibility, and its stability under in-vivo conditions. Alginate polymer is a natural polysaccharide derived from brown seaweed and has the ability to polymerize rapidly in the presence of cations to form a porous matrix. In order to advance the previous system for efficient protein and peptide delivery, we further lyophilized the peptide-filled microcapsules and we were able to rehydrate, and test them for sustained …

The Impact Of Communication Deficits On Puberty And Sexual Development In Adolescents On The Autism Spectrum, Ashton Wolfe

Theses and Dissertations

Transitioning into a sexually mature adult is a challenging time for both an adolescent with autism spectrum disorder (ASD) and his or her family. Sexual development begets challenges due to the demands it places on the social and communication skills needed to explore developmental changes that are occurring physically, emotionally and hormonally. A diagnosis of ASD is largely established by quantifying impediments in social and communication skills through observation. With deficits in these skills, one can assume that social and communication difficulties can create obstacles in the sexual development of affected individuals. Our study used quantitative and qualitative measures to …

Development Of A High-Resolution Spatial Heterodyne Libs Spectrometer, Kevin A. Dudley

Theses and Dissertations

Laser-Induced Breakdown Spectroscopy (LIBS) is an atomic emission technique that uses a pulse laser to ablate a sample and form a plasma. Atomic emissions from the plasma provide unique elemental characteristics regarding the composition of the sample. The technique produces valuable qualitative results, but the accuracy of quantitative analyses is hindered by spectral line broadening mechanisms and laser pulse reproducibility, among other factors. The Spatial Heterodyne Spectrometer (SHS) is a high-resolution spectrometer with very high light throughput, and its use to LIBS is currently limited to two peer-reviewed publications. In the following work a high resolution SHS is developed and …

Environmental Impacts On Enterococcus In Shem Creek, South Carolina, And Characterization Of Changing Land Use, Maria Elizabeth Zubizarreta

Theses and Dissertations

Zoning and land-use practices have a direct influence on hydrologic systems and can impact water resources. Linkages between change in land uses and degradation of water quality in stream and watershed environments have been well established. Shem Creek, located in Mount Pleasant, SC, has a history of fecal indicator bacteria levels that exceed the Environmental Protection Agency’s recreational water quality standards. With recent coastal population and development trends, proper management and the sustainability of beach and estuary environments are a rising public health concern. The objective of this study is to determine what climatic and water quality parameters are associated …

Matrix Stiffness Modulates Mesenchymal Stem Cell Sensitivity To Geometric Asymmetry Signals, Maria Eugenia Piroli

Theses and Dissertations

Human stem cells hold significant potential for the treatment of various diseases. However, their use as a therapy is hampered by the limited understanding of the mechanisms by which stem cells respond to environmental stimuli. Efforts to understand extracellular biophysical cues have demonstrated the critical roles of geometric and mechanical signals in determining the fate of stem cells. The goal of this study was to explore the interplay between cell polarity and matrix stiffness in stem cell lineage specification. We hypothesize that confining cells to asymmetric extracellular matrix (ECM) islands will impart polarity at a single-cell level and result in …

Plants As Biofactories To Produce Mammalian Tumor Suppressor Micrornas, John Lachlan Macarthur

Theses and Dissertations

MicroRNAs (miRNAs) are small noncoding single stranded RNAs that are considered master regulators of gene expression. They are also an emerging class of therapeutic agents with significant potential for the prevention and treatment of many diseases, including cancer. Many different forms of cancer are associated with loss or reduced accumulation of one or more miRNAs that function as tumor suppressors. In animal models, restoration of missing tumor suppressor miRNAs prevents the initiation, progression and/or spread of the disease. However, the current absence of an efficient method for delivery of therapeutic miRNAs is a critical barrier to their use. The research …

Chronic Conditions Profiles And Cardiometabolic Risk Factor Control Among A Diverse Sample Of Older Adults With Type 2 Diabetes Mellitus, Tsion Kidanie

Theses and Dissertations

Background: Multiple chronic condition is common in older adults with diabetes. Several prior studies have shown that having multiple chronic condition impact cardiometabolic risk factor controls (i.e., blood pressure, High-density lipoprotein (HDL) cholesterol level, and high glycated hemoglobin (HbA1c). However, it is not clear whether these results extend to a multiethnic sample of older adults.

Objectives: 1). Examine the association between Comorbidity profile and ABCs goals achievement. 2). Examine whether the association between comorbidity profile and ABCs goals achievement is moderated by race/ethnicity.

Methods: A sample of 3532 participants from Health and Retirement Study (HRS) years 2010 and 2012 and …

Epistemological Issues In Quality Of Life Measurement And Their Implications, Laura M. Cupples

Theses and Dissertations

This project explores the epistemology of quality of life measurement. Quality of life measures face a dual epistemic burden both to serve as data for the evidence-based medicine movement and to give patients a greater voice (McClimans 2017). Much time, effort, and money has been invested in these measures over the last 50 years, and yet their theoretical foundations remain weak. It is not clear whether these instruments succeed in measuring what they purport to measure, or what precisely is meant by “quality of life” (Hunt 1997). The epistemic challenges faced in quality of life measurement are not wholly unique. …

Initiating A Peer Support Program For Parents Of Children With Autism Spectrum Disorder In Richland And Lexington Counties, Danielle P. Simmons

Theses and Dissertations

Objective: To initiate a parenting support program for parents of children with Autism Spectrum Disorder (ASD) in Richland and Lexington Counties. Background: Parents of children with ASD have increased stress and a poorer sense of well-being relative to parents of children with typical development. This parent population in Richland and Lexington Counties identified lack of support as a major stressor. The parenting support model initiated (e.g. Parent to Parent program) is an evidence-based intervention used to provide peer support to parents of children with ASD. The training of veteran parents is essential in the development and initiation of a Parent …

Influence Of Energy Availability On The Carbon Isotopes Of Methane And Biomarkers During Hydrogenotrophic Methanogenesis, Tran Nguyen

Theses and Dissertations

Signatures of organic molecules in the environment are widely used to identify microbial metabolic processes and to track the cycling of carbon. The lipid biomarkers of methane cycling archaea are of particular interest as they are unique, preserved over geologic time scales, and reflect processes that impact an important greenhouse gas. Their isotopic compositions have been used to distinguish regions where archaea produce and anaerobically consume CH4. Previous work has demonstrated that energy availability impacts the stable carbon isotopes of CH4 during microbial synthesis from H2 and CO2. Here, we investigated whether this relationship could be extended to lipids and …

Linking Microbial Phylogenetic And Functional Gene Diversity To Microbial Mat Ecosystem Function Following Environmental Disturbance, Eva Christine Preisner

Theses and Dissertations

The ability of ecosystems to adapt to environmental perturbations depends on the duration and intensity of change and the overall biological diversity of the system. In this study, a microbial mat ecosystem located on San Salvador Island, the Bahamas was used as a model to examine how environmental disturbance affects microbial community resistance, their protein synthesis potential (PSP), ecosystem function as measured by biogeochemical cycling, community stability, and resilience. This ecosystem experienced a large shift in salinity (230 to 65 g kg-1) during 2011–2012 following the landfall of Hurricane Irene on San Salvador Island. High throughput sequencing and analysis of …

Comparison Of The Performance Of Simple Linear Regression And Quantile Regression With Non-Normal Data: A Simulation Study, Marjorie Howard

Theses and Dissertations

Linear regression is a widely used method for analysis that is well understood across a wide variety of disciplines. In order to use linear regression, a number of assumptions must be met. These assumptions, specifically normality and homoscedasticity of the error distribution can at best be met only approximately with real data. Quantile regression requires fewer assumptions, which offers a potential advantage over linear regression. In this simulation study, we compare the performance of linear (least squares) regression to quantile regression when these assumptions are violated, in order to investigate under what conditions quantile regression becomes the more advantageous method …

Effects Of Diabetes On Ovarian Cancer: Data Analysis And Modeling Study, Claire Belay

Theses and Dissertations

Ovarian cancer has one of the highest mortality rates of all gynecological cancers [13]. Further knowledge of risk factors for the growth of ovarian tumors would be beneficial in both the treatment and prevention of this type of cancer. Previous research has shown a positive correlation between diabetes and prostate tumor growth [22], The first aim of this study was to determine the effect of diabetes of ovarian tumor growth. The second aim was to develop a model to predict ovarian tumor growth based on the microenvironment within a patient’s body. The hypothesis was that there would be a positive …

Correlation Of Aqueous Solubility And Anti-Cancer Activity Of Novel Triazolium And Imidazolium Salts, Jared J. Bies

Theses and Dissertations

Novel triazolium, imidazolium, and benzimidazolium salts are known to possess anti-cancer properties and have potential as cancer therapeutics. This thesis describes the aqueous solubility and the differential activity of N,AT-bis-substituted-l,2,4-triazolium bromide salts and N/N'-bis(naphthylmethyl)imidazolium bromide salts against MDA-MB-468 breast cancer cells and PC-3 prostate carcinomas. Using a microscale technique, the partition coefficient (log P) of each salt was determined. The log P value was explored to determine the bioavailability of each derivative.

On Nature's Prototypes: Character Design And Worldbuilding, Taylor J. Bardon

Theses and Dissertations

Nature’s Prototypes is an ongoing narrative series that blends realism and fiction to create both dialectic plot structures and image sets. For substance, the series utilizes biological inquiries into fields, like ecology, pathology, and bioengineering, to imagine action-centric vignettes, where animalistic to monstrous characters become the predominant actors in a post-dystopian worldscape. Throughout these vignettes, these characters are subjected to the trials and tribulations of the catalysts and flux that are imposed upon them. In the series’ larger scope, these vignettes are sequential events within a larger timeline and an original mythos that delve into the implications and the intrigue …

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 …

"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 …

Toxicological Inhalation Effects Of Metal-Based Nanoparticle Aerosols As Studied By A Portable In Vitro Exposure Cassette, Lynn E. Secondo

Theses and Dissertations

The toxicology of aerosols in occupational settings is often performed through particle collection on a filter followed by reconstitution into cell culture media which can alter the biological effects. Current in vitro exposure systems require additional instruments to control temperature and humidity, making the system bulky and difficult to take to the field. The Portable In Vitro Exposure Cassette (PIVEC) was designed for personal monitoring, characterized using copper nanoparticles, tested with alveolar cells, and set-up for real-time monitoring. Three differently sized copper nanoparticles, 40-800 nm, were dispersed as a dry aerosol and measured gravimetrically and on a number concentration basis …

A Comparison Of The Antimicrobial Efficacy Of Silver Diamine Fluoride And Silver Nitrate: An Ex Vivo Study, Reham M. Alnajjar

Theses and Dissertations

A comparison of the antimicrobial efficacy of silver diamine fluoride and silver nitrate on various cariogenic bacteria: an ex vivo study By: Reham AlNajjar, 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, 2019

Thesis Advisor: William Dahlke, D.M.D., Associate Professor and Chair of Pediatric Dentistry, School of Dentistry

Purpose: The use of silver-based antimicrobials is an emerging method for the treatment of dental caries. In this study, the authors compare the efficacy of the two most prominent silver- based therapeutics, silver diamine …

Activation Of Trpv1 By Capsaicin Regulates Enac, Alexander Saffran

Theses and Dissertations

ENaC is a constitutively open heterotrimeric channel which regulates Na⁺ transport in tight epithelia of the kidney, lungs, colon and anterior tongue containing fungiform taste buds. The amiloride-sensitive ENaC is comprised of aβg subunits. Humans express an additional subunit, the d subunit. Therefore, humans contain both aβg-ENaC and dβg-ENaC functional channels. Relative to aβg-ENaC, the dβg-ENaC is 10-fold less sensitive to amiloride. In the mammalian anterior tongue, ENaC is expressed in fungiform salt sensing taste receptor cells and is the Na⁺-specific salt taste receptor. In mammals, salt elicits an inverted U shaped behavioral response. Lower concentrations of …

Motion-Induced Artifact Mitigation And Image Enhancement Strategies For Four-Dimensional Fan-Beam And Cone-Beam Computed Tomography, Matthew J. Riblett

Theses and Dissertations

Four dimensional imaging has become part of the standard of care for diagnosing and treating non-small cell lung cancer. In radiotherapy applications 4D fan-beam computed tomography (4D-CT) and 4D cone-beam computed tomography (4D-CBCT) are two advanced imaging modalities that afford clinical practitioners knowledge of the underlying kinematics and structural dynamics of diseased tissues and provide insight into the effects of regular organ motion and the nature of tissue deformation over time. While these imaging techniques can facilitate the use of more targeted radiotherapies, issues surrounding image quality and accuracy currently limit the utility of these images clinically.

The purpose of …

Mass Spectrometry-Based Proteomics Analysis Of Secreted Proteins, Emmanuel K. Cudjoe Jr

Theses and Dissertations

Secreted proteins play important roles in many cellular functions and molecular processes. Because secreted proteins potentially enter the blood stream, they can serve as valuable measures of health and disease useful for disease diagnosis and prognosis, therapeutic target identification, and patient stratification in personalized medicine. Consequently, significant interest exists in secreted protein analysis within complex biospecimens, particularly blood but significant bioanalytical challenges including the wide protein dynamic range >10 orders of magnitude remain. The cellular secretome therefore represents a viable alternative to direct biomarker discovery in biofluids. Finally, cellular systems are amenable to labeling for the production of intact stable …

Periodontal Therapy Improves Oral And Gut Microbiota And Reduces Systemic Inflammation And Endotoxemia In Patients With Cirrhosis, Payam Matin

Theses and Dissertations

Objectives: The aim of this pilot study was to compare the changes in oral and gut microbiota, endotoxemia, and systemic and local inflammatory markers following oral interventions in subjects with and without cirrhosis.

Methods: Study subjects displaying gingivitis or mild/moderate periodontitis were placed into two groups: with cirrhosis (n= 24) and without cirrhosis (n=21). Each subject received nonsurgical periodontal therapy. Serum, stool and saliva samples were collected prior to and 30 days post-therapy and analyzed for stool/saliva microbiome, MELD score, endotoxin and IL-6 levels.

Results: There was no difference in age, gender and the periodontal disease status between groups. At …

Impact Of Aerobic Exercise On Monocyte Subset Receptor Expression And Macrophage Polarization, Anson M. Blanks

Theses and Dissertations

Atherosclerotic cardiovascular disease (CVD) is hallmarked by inflammatory immune activation, particularly by the induction of a response by monocytes. Classical (CD14⁺⁺CD16^-) are anti-inflammatory mediators under homeostatic conditions, while intermediate (CD14⁺⁺CD16⁺) and non-classical (CD14^LowCD16⁺⁺) monocytes promote inflammation following activation. Monocyte activation and functionality is dependent upon receptor expression and ligand production by a variety of cells, including monocytes. Alterations in the expression of surface receptors often have a direct impact upon monocyte function, such as the increased pro-inflammatory cytokine production in response to activation that accompanies elevated CD14 expression …

Discovering Driver Mutations In Biological Data, Yahya Bokhari

Theses and Dissertations

Background

Somatic mutations accumulate in human cells throughout life. Some may have no adverse consequences, but some of them may lead to cancer. A cancer genome is typically unstable, and thus more mutations can accumulate in the DNA of cancer cells. An ongoing problem is to figure out which mutations are drivers - play a role in oncogenesis, and which are passengers - do not play a role. One way of addressing this question is through inspection of somatic mutations in DNA of cancer samples from a cohort of patients and detection of patterns that differentiate driver from passenger mutations. …

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. …

Discrimination, Mental Health, And Preparedness For Aging In Trans(Gender)/Gender-Nonconforming Adults, Richard S. Henry

Theses and Dissertations

This cross-sectional study examined relationships among discrimination, mental health (i.e., depression and anxiety), preparation for aging (i.e., familiarity and planning), social support, death attitudes, and aging anxiety among TGNC adults (N = 154). Neither discrimination nor mental health predicted preparation for aging familiarity or planning. Discrimination did, however, predict both anxiety and depression, although only the non-affirmation subscale was a unique predictor of both. As discrimination and mental health were not a significant predictor of preparedness for aging in the previous regressions, the hypothesized mediation model and subsequent moderated mediation models were not conducted. Additional exploratory multiple regressions were …

Lanthanide-Based Core-Shell Nanoparticles As Multifunctional Platforms For Targeted Radionuclide Therapy And Multimodal Molecular Imaging, Miguel Toro-Gonzalez

Theses and Dissertations

Lanthanide phosphate (LnPO₄) and lanthanide vanadate (LnVO₄) nanoparticles (NPs) are promising platforms for theranostic applications because of their chemical stability, low solubility, low toxicity, and unique luminescence and magnetic properties. Motivated by the high radiation resistance and ability to host actinides of naturally occurring lanthanide-based compounds, LnPO₄ and LnVO₄ NPs were studied as radionuclide carriers for targeted radionuclide therapy using in vivoα-generators, ²²³Ra, ²²⁵Ac, and ²²⁷Th. The implementation of these radionuclides has shown potential for the treatment of micrometastases and solid tumors as well as challenges in the retention of …

Quantitative And Molecular Analysis Of Habituation At The Maize R1 Locus, Robert C. Lindsay

Theses and Dissertations

Epigenetics is the study of heritable changes in phenotypes that are not the result of changes in DNA sequence. Examples of epigenetic affecters include methylation changes, chromatin modifications, transcription factors, and RNA-based changes. The molecular mechanisms behind epigenetic changes are not fully understood. Canalization is the buffering of gene expression against environmental changes over time, while habituation is semi-stable expression change over time due to selection. This work characterized the molecular changes associated with the kernel color changes of the R-sc:86-17pale allele at the maize red color1 (r1) locus to determine if the changes are epigenetic in nature. …