Medicine and Health Sciences Commons^™

Soil Arsenic And Lead Concentrations And Preterm Birth: Investigating Racial Disparities, Sources, Neighborhood Effects, And Spatial Patterns, Pamela Harley Thornton Davis

Theses and Dissertations

Preterm birth, generally defined as birth at <37 weeks of gestation, is an important public health issue that has multiple risk factors related to characteristics of both the mother and her environment. The purpose of this dissertation was to examine potential sources of spatially interpolated (kriged) environmental concentrations of arsenic (As) and lead (Pb) in residential soils and preterm birth in a Medicaid population of mothers giving birth in South Carolina (SC) from 1996-2001. The first objective was to investigate if a racial disparity existed for estimated soil As and Pb concentrations, after adjusting for proximal and distal sources of these metals (including distance and direction to industrial facilities) in a subset of SC Medicaid mothers living in areas of SC where soil samples were collected and analyzed for these metals. The second objective was to test the hypothesis that estimated soil As and Pb concentrations were associated with increased odds of early (<34 weeks) and late (34-36 weeks) preterm births in the same subset of SC Medicaid mothers, after adjusting for individual and neighborhood level risk factors, and examine if measure of neighborhood deprivation and racial residential segregation modified these associations. The third objective was to examine if early and all preterm births, aggregated at the county level, varied spatially and/or temporally in SC for all Medicaid mothers giving birth from 1996-2001 in Bayesian models.

For the first objective, black mothers had significantly higher estimated As and Pb soil concentrations than white mothers in the study population (adjusted betas were 0.12 and 0.22 for As and Pb, respectively; all p<0.006), and proximal sources of metals (e.g., percent of Census block group are covered by roads) were more strongly associated with estimated soil As and Pb concentrations than composite As and Pb releases from industrial facilities categorized by distance from and direction to Census block groups in which maternal residences were located.

For the second objective, estimated soil concentration of neither As nor Pb were associated with increased odds of early or late preterm birth after adjusting for maternal and neighborhood level risk factors. Only individual level covariates were associated with these birth outcomes, and associations were stronger for early as compared to late preterm births. Neighborhood deprivation and racial …

Longitudinal Association Between Television Watching, Computer Use And Meal Frequency And Risk Markers In Diabetes Among Youth With Diabetes, Chao Li

Theses and Dissertations

BACKGROUND AND OBJECTIVES: Television watching and computer use are considered to be the main sedentary behaviors in children and youth. However, their longitudinal impact on HbA1c and serum lipids among youth with type 1 diabetes (T1D) and type 2 diabetes (T2D) are under-studied. Sedentary behavior is normally assessed by questionnaire in large epidemiological studies, however, its measurement by questionnaire has not been evaluated among youth with diabetes. Also, no recent studies have evaluated the optimal meal frequency for glycemic control in youth with T1D and T2D; for this reason nutritional guidelines on meal frequency for youth with diabetes are vague. …

The Influence Of Self-Reported Degree Of Masculinity/Femininity On Condom Use Among Black Men Who Have Sex With Men In The Deep South, Elizabeth D. Peeler

Theses and Dissertations

In the United States, 50,000 Americans are diagnosed with HIV each year (CDCa, 2014). The HIV/AIDS epidemic has had a particularly devastating impact on the southern U.S., especially the Deep South – Alabama, Georgia, Louisiana, Mississippi, North Carolina, and South Carolina (Reif, Whetten, Wilson, McAllaster, Pence, Legrand, & Gong, 2014). The Deep South, while only composing of 36% of the national population, accounts for 50% of all people living with HIV/AIDS in the nation (Human Rights Watch, 2010). No other population has been hit harder than men who have sex with men (MSM; Prejean, Tang, & hall, 2013). Black MSM …

Examination Of The Association Of Receipt Of Opioid Therapy And Lung Cancer Patient Survival Rates Among South Carolina Medicaid Recipients, Jametta Sade Magwood

Theses and Dissertations

Introduction: Lung cancer is a high pain cancer that can require the attention of clinical specialists. Already vulnerable populations, like those that inhabit rural areas, when dealing with chronic diseases, like lung cancer, need and deserve adequate medical attention. However, rural communities often lack clinical specialists and are left without the needed care. It is necessary to investigate the current availability of treatment options (medications) available to cancer patients in rural communities. Gaining this knowledge can result in economic savings and improvement of the quality of life for rural populations.

Methods: Medicaid data from 1996-2010 was used to …

Interpregnancy Weight Change And Adverse Maternal Outcomes, Chelsea Lynes

Theses and Dissertations

Obesity during pregnancy is associated with a high risk of adverse maternal outcomes. Little is known about how weight change between consecutive pregnancies impacts subsequent pregnancy complications and newborn outcomes. This study aimed to explore the association between interpregnancy BMI change and adverse maternal outcomes, specifically, gestational diabetes mellitus (GDM), gestational hypertension, pre-eclampsia, non-repeat cesarean delivery (C-section), and vaginal birth after cesarean delivery (VBAC). The study sample was derived from the Eunice Kennedy Shriver National Institute of Child Health and Human Development Consecutive Pregnancy Study, which collected data from 20 hospitals in Utah utilizing electronic medical records and International Classification …

The Characterization Of A Putative Protease Expressed By Sneathia Amnii, Rana Mehr

Theses and Dissertations

Preterm birth, birth prior to 37 weeks gestation, is the leading cause of neonatal mortality and morbidity worldwide. While the uterine cavity and amniotic fluid largely remain sterile throughout gestation, bacterial infections can occur and are associated with preterm birth and/or preterm premature rupture of the fetal membranes (PPROM). Sneathia amnii can be detected as a component of the vaginal flora in healthy women; however, it’s also associated with bacterial vaginosis and preterm birth. Sn35, an isolate of S.amnii, was identified and sequenced through the Vaginal Human Microbiome Project at VCU. Our objective was to classify potential virulence determinants …

Targeting Autophagy In Multiple Myeloma, Yun Dai

Theses and Dissertations

Apoptosis (Type I) and autophagy (Type II) represent two major forms of programmed cell death. Numerous anticancer agents employed in standard chemotherapy or novel targeted therapy induce both apoptosis and autophagy. Of note, a cytoprotective autophagic response often counteracts apoptosis triggered by such agents, potentially contributing to drug-resistance. Mechanistically, autophagy and apoptosis share molecular regulatory mechanisms primarily governed by the Bcl-2 family proteins. However, since autophagy acts as the double-edge sword in cancer, whether autophagy should be inhibited or activated in cancer treatment remains the subject of debate. Here we report a) a novel autophagy-targeted strategy that targeting the adaptor …

Immunotherapy Of Cancer: Reprogramming Tumor/Immune Cellular Crosstalk To Improve Anti-Tumor Efficacy, Kyle K. Payne

Theses and Dissertations

Immunotherapy of cancer has been shown to be promising in prolonging patient survival. However, complete elimination of cancer and life-long relapse-free survival remain to be major challenge for anti-cancer therapeutics. We have previously reported that ex vivo reprogramming of tumor-sensitized immune cells by bryostatin 1/ionomycin (B/I) and the gamma-chain (γ-c) cytokines IL-2, IL-7, and IL-15 resulted in the generation of memory T cells as well as CD25+ NKT cells and CD25+ NK cells. Adoptive cellular therapy (ACT) utilizing these reprogrammed immune cells protected FVBN202 mice from tumor challenge, and overcame the suppressive functions of myeloid-derived suppressor cells (MDSCs). We then …

Impact Of E-Cigarettes On Physician Recommendations Of Tobacco Use Cessation Pharmacotherapy, Omar El Shahawy

Theses and Dissertations

Introduction: E-cigarettes have been marketed as smoking cessation aids and harm reduction strategies. Prior regional surveys found that physicians are recommending them to patients despite the lack of evidence supporting these industry claims. Yet, little is known about physicians’ beliefs regarding e-cigarettes and whether these beliefs are associated with them recommending e-cigarette use in clinical practice. Methods: This three-manuscript dissertation used a mixed-methods approach including both qualitative and quantitative research methods. The aims were to: (1) Uncover the factors associated with primary care physicians’ (PCPs) decisions to recommend e-cigarettes to their patients for tobacco use cessation; (2) Estimate the prevalence …

Investigation Of Phenylephrine Sulfation And Inhibition Using A Novel Hilic Assay Method, Heta N. Shah

Theses and Dissertations

Phenylephrine (PE) is the most commonly used over-the-counter nasal decongestant. The problem associated with phenylephrine is that it undergoes extensive first pass metabolism in the intestinal gut wall leading to its poor and variable oral bioavailability.

This research project aims at developing strategies in order to increase the oral bioavailability of PE by co-administration of GRAS compounds. A HILIC assay method was developed to detect the parent drug, phenylephrine (PE) and its sulfate metabolite (PES).The enzyme kinetic studies were done with phenolic dietary or GRAS compounds using LS180 human intestinal cell model, recombinant SULT enzymes and human intestinal cytosol (HIC). …

Mirnas As Biomarkers For Prostate Cancer Progression, Gene C. Clark

Theses and Dissertations

Prostate cancer is one of the most challenging global medical issues today. In 2011, prostate cancer was the most diagnosed malignancy in the United States, making up 29% of new cancer cases. In that year it was the second leading cause of cancer related deaths among men in the USA and the second most common cause of cancer related death overall from the EU. The prostate remains, however, an under studied organ, making insights into the anatomy and biology of prostate cancer difficult to achieve. After 30 years, PSA screening of men of the appropriate age is still the first …

Relational Coordination: An Exploration Of Nursing Units, An Emergency Department And In-Patient Transfers, Mary Coffey

Theses and Dissertations

Emergency department (ED) crowding is a patient safety concern that has been increasing for more than a decade. Increased visits have resulted in ED crowding, longer wait times, ambulance diversions, and boarding of admitted patients (Hing & Bhuiya, 2012). Numerous factors affect ED crowding. Once various extraneous issues are resolved and a bed is available for a patient, it becomes the responsibility of nurses across unit boundaries to coordinate the patient transfer. This study applies Relational Coordination Theory (RCT) as a framework to provide nurses insight into the relational aspects of their work in the transfer of ED patients to …

Enhancement Of The Placental Transmission Of Lopinavir Using A Transporter Targeted Prodrug Strategy, Meng Wang

Theses and Dissertations

Lopinavir (LPV) is a potent protease inhibitor specific for HIV-1. However, LPV has poor placental penetration due to substrate activity for efflux transporter by P-glycoprotein (P-gp). Since fatty acid transporters are highly expressed in the placenta during pregnancy, we designed fatty acid ester prodrug of lopinavir as substrates of fatty acid transporter in order to improve their uptake into placenta. Seven dicarboxylic acid esters of lopinavir have been made in our lab. The structures were characterized by ¹H-NMR, ¹³C-NMR, LC-MS/MS, HRMS, IR and melting points. After making the prodrugs, an LC-MS/MS method with high specificity and sensitivity, as …

Characterizarion Of The Regulation And Function Of Neisseria Gonorrhoeae Tonb-Dependent Transporters: Tdfg, Tdfh And Tdfj, Sophonie Jean

Theses and Dissertations

The obligate human pathogen Neisseria gonorrhoeae successfully overcomes host strategies to limit essential nutrients, termed “nutritional immunity” by expression of TonB-dependent transporters (TdTs): outer membrane receptors that facilitate nutrient transport in an energy-dependent manner. N. gonorrhoeae encodes eight TdTs, five of which facilitate utilization of iron or iron-chelates from host derived proteins including transferrin, lactoferrin and hemoglobin, in addition to siderophores from neighboring bacteria. The transferrin utilization system was previously shown to be critical for establishing infection in human males; demonstrating the possible contributions of TdTs to gonococcal pathogenesis. As such, studies describing the biological function and contribution to pathogenesis …

Generation And Delivery Of Charged Aerosols To Infant Airways, Landon T. Holbrook

Theses and Dissertations

The administration of pharmaceutical aerosols to infants on mechanical ventilation needs to be improved by increasing the efficiency of delivery devices and creating better ways of evaluating potential therapies. Aerosolized medicines such as surfactants have been administered to ventilated infants with mixed results, but studies have shown improvement in respiratory function with a much lower dose than with liquid instillation through an endotracheal tube (ETT). An aerosolized medicine must be transported through the ventilation tubing and deposit in the lungs to have the desired therapeutic response.

This work has taken a systematic approach to (i) develop new devices for the …

Effects Of Brain-Derived Neurotrophic Factor And Its Signaling Pathway On Sensory Neuronal Activation During Colitis, Fiza Hashmi

Theses and Dissertations

Visceral hypersensitivity is the heightened response to sensory stimuli. Visceral sensations are transmitted through primary afferent neurons in the dorsal root ganglion (DRG) and the sensitization of the neural pathway leads to modification in spinal ascending and descending neurons. The aim of this investigation is to determine the effects of brain-derived neurotrophic factor (BDNF) and its signaling pathway on sensory neuronal activation during colitis. In order to evaluate this, levels of calcitonin-gene related peptide (CGRP), a neuropeptide marker for nociceptive transmission, and phosphorylated cAMP-response element binding protein (pCREB), a molecular switch in neuronal plasticity, were studied in response to BDNF …

Xlf-Dependent Nonhomologous End Joining Of Complex Dna Double-Strand Breaks With Proximal Thymine Glycol And Screening For Xrcc4-Xlf Interaction Inhibitors, Mohammed Al Mohaini

Theses and Dissertations

DNA double-strand breaks induced by ionizing radiation are often accompanied by ancillary oxidative base damage that may prevent or delay their repair. In order to better define the features that make some DSBs repair-resistant, XLF-dependent nonhomologous end joining of blunt-ended DSB substrates having the oxidatively modified nonplanar base thymine glycol (Tg) at the first (Tg1) , second (Tg2), third (Tg3) or fifth (Tg5) positions from one 3’ terminus was examined in human whole-cell extracts. Tg at the third position had little effect on end-joining even when present on both ends of the break. However, Tg as the terminal or penultimate …

The Characterization Of A Putative Virulence Factor Expressed By Sneathia Amnii, Amy Sanford

Theses and Dissertations

Preterm birth, defined at birth before 37 weeks gestation, affects millions of newborns worldwide every year. Preterm birth is a leading cause of infant morbidity and mortality. One major cause of preterm birth is preterm premature rupture of membranes (PPROM), which can be triggered by bacterial infection and inflammation. A bacterial species that has been implicated in preterm birth and other obstetric complications is Sneathia amnii. The goals of this study were to observe cytopathogenic effects caused by S. amnii strain Sn35 and identify putative virulence factors causing those effects. Sn35 was able to adhere to, invade, and damage/kill …

Effects Of Hiv-1 Viral Protein Tat On The Viability And Function Of Oligodendroglial Cells, Shiping Zou

Theses and Dissertations

Myelin pallor is frequently reported in HIV patients, and can occur in the CNS prior to other evidence of disease process. Our exploratory studies showed that oligodendrocytes (OLs) are direct targets of HIV-1 Tat (transactivator of transcription). Tat induces a dose-dependent increase of intracellular Ca²⁺ level ([Ca²⁺]_i) in cultured murine OLs, which can be attenuated by ionotropic glutamate receptor (iGluR) antagonists MK801 and CNQX. The Tat-induced [Ca²⁺]_i increase leads to increased death in immature (O4⁺, MBP^-), but not mature (O4⁺, MBP⁺) OLs, over 96 …

Computational Modeling To Assess Surgical Procedures For The Treatment Of Adult Acquired Flatfoot Deformity, Brian A. Smith

Theses and Dissertations

Several surgically corrective procedures are considered to treat Adult Acquired Flatfoot Deformity (AAFD) patients, relieve pain, and restore function. Procedure selection is based on best practices and surgeon preference. Recent research created patient specific models of Adult Acquired Flatfoot Deformity (AAFD) to explore their predictive capabilities and examine effectiveness of the surgical procedure used to treat the deformity. The models’ behavior was governed solely by patient bodyweight, soft tissue constraints, and joint contact without the assumption of idealized joints. The current work expanded those models to determine if an alternate procedure would be more effective for the individual. These procedures …

The Role Of Α3Β4* Subtype Of Nicotinic Acetylcholine Receptors In Reversing Opioid-Induced Constipation In Mice, Aravind Gade

Theses and Dissertations

Opioids are excellent pain relievers. A major side-effect of chronic opioid treatment is constipation whereas withdrawal following chronic exposure leads to diarrhea and increased gastrointestinal motility. These effects of chronic opioids are mediated by μ-opioid receptors expressed on enteric neurons. Previous studies have shown that chronic opioids enhance sensitivity to nicotine in the gastrointestinal tract. This suggested that prokinetic effects of nicotine mediated through the activation of nicotinic acetylcholine receptors (nAChRs) may be useful in reversing opioid-induced constipation. The goal of this dissertation was to investigate the nAChR subtype expressed on enteric neurons and their role in reversing opioid-induced constipation. …

Meta-Analysis Of Gene Expression Studies, Umaporn Siangphoe

Theses and Dissertations

Combining effect sizes from individual studies using random-effects models are commonly applied in high-dimensional gene expression data. However, unknown study heterogeneity can arise from inconsistency of sample qualities and experimental conditions. High heterogeneity of effect sizes can reduce statistical power of the models. We proposed two new methods for random effects estimation and measurements for model variation and strength of the study heterogeneity. We then developed a statistical technique to test for significance of random effects and identify heterogeneous genes. We also proposed another meta-analytic approach that incorporates informative weights in the random effects meta-analysis models. We compared the proposed …

Psychoactive Synthetic Cathinones (Or 'Bath Salts'): Investigation Of Mechanisms Of Action, Farhana Sakloth

Theses and Dissertations

Synthetic cathinones represent threatening and high abuse-potential designer drugs. These are analogs of cathinone (the b-keto analog of amphetamine (AMPH)) a naturally occurring stimulant found in the plant Catha Edulis. Methcathinone (MCAT) was the first synthetic analog of cathinone to be identified in 1987 by Glennon and co-workers and it exerted its action primarily through the dopamine transporter (DAT). Most central stimulants exert their action via monomaine transporters by causing either the release (e.g. cathinone analogs such as MCAT) or by preventing the reuptake (e.g. cocaine) of the neurotransmitter dopamine (DA) thus increasing the extracellular synaptosomal concentration of this …

Interaction Between Atm Kinase And P53 In Determining Glioma Radiosensitivity, Syed F. Ahmad

Theses and Dissertations

Glioblastoma multiforme (GBM) is the most common primary brain tumor. Studies have shown that targeting the DNA damage response can sensitize cancer cells to DNA damaging agents. Ataxia telangiectasia mutated (ATM) is involved in signaling DNA double strand breaks. Our group has previously shown that ATM inhibitors (ATMi) sensitize GBM cells and tumors to ionizing radiation. This effect is greater when the tumor suppressor p53 is mutated.

The goals of this work include validation of a new ATM inhibitor, AZ32, and elucidation of how ATMi and p53 status interact to promote cell death after radiation. We propose that ATMi and …

Factors That Influence Breast Cancer Diagnoses In Virginia Women 40-64 Years Old Who Utlized The Every Woman’S Life Program 1998-2012, Melanie C. Dempsey

Theses and Dissertations

This dissertation examines sociodemographic determinants and preventive health behaviors among women 40-64 years of age who participated in the Virginia Department of Health’s Every Woman’s Life breast cancer screening program. Utilizing secondary data, this research sought to explore patterns of breast cancer incidence, mammography screening utilization and sources of health information among low-income women.

The Virginia Department of Health provided a large sample size (N=34,942) on which to perform binary logistic regression analyses. Sociodemographic determinants and preventive health behaviors were analyzed as potential influencing factors in the diagnosis of breast cancer, the stage at the time of diagnosis and source …

Measuring The Impact Of Recognized Patient-Centered Medical Homes (Pcmh), Rick Moore

Theses and Dissertations

This dissertation proposal seeks to understand if the increasingnumbers (density) of recognized PCMH practices incommunities affect avoidable hospitalizations related toambulatory care sensitive conditions (ACSC), as measured bythe AHRQ Composite Prevention Quality Indicators (PQI). Theresearch has two purposes: 1. Establish constructs and hypotheses to measurethe effect of the increasing numbers of NCQA-Recognized PCMH practices in communities(counties). 2. Using an outcomes-based measurement approach,investigate the relationship between growingdensities of NCQA-Recognized PCMH practicedoctors among all primary care doctors (PCD) ina community and the associated impact on theutilization of inpatient care, specifically related toACSCs, as measured by the AHRQ CompositePQIs.

The research is quasi-experimental in …

Individuals With Fetal Alcohol Spectrum Disorder: Predictive Factors For Successful Occupational Performance, Mary Culshaw

Theses and Dissertations

As awareness and diagnoses of FASD grow in Canada, there is increased need to support these individuals across their lifespan. One study suggested the prevalence of FASD may be as high as 10 per 1000 births (May & Gossage, 2001). The impact to society is growing as well, since this population requires support across their lifespan due to cognitive and sometimes physical impairments. It was estimated that the annual cost to Canadians was $53 billion (in 2007 dollar value) to support individuals aged 0-53 years (Stade et al., 2009). There is mounting evidence identifying the cognitive and physical impairments that …

Conduction States Of The Human Dopamine Transporter, Krasnodara Cameron

Theses and Dissertations

Dysregulation of dopaminergic homeostasis has been established as the primary source of numerous neurological disorders including Parkinson’s and drug addiction. A tonic increase of dopamine (DA) in the nucleus accumbens is required for associating everyday events and behaviors with rewards. Yet many addictive exogenous compounds such as amphetamine (AMPH) and cocaine (COC) produce a much greater augmentation of synaptic DA levels that are linked to euphoria and a shift in behavior towards drug seeking. The protein responsible for maintaining extracellular levels of DA is the dopamine transporter (DAT). It is primarily located in the perisynaptic area at terminals of pre-synaptic …

Vitamin C: A Potential Regulator Of Inflammatory Response, Bassem M. Mohammed

Theses and Dissertations

Introduction: Neutrophils (PMNs) and Macrophages are the first responders recruited consecutively to the site of injury/inflammation. PMNs’ response/fate as well as macrophage reprogramming ultimately determine the course of resolution of inflammation. Physiologic wound healing has a significant inflammatory component. An exaggerated inflammation however is self-defeating leading to delayed healing. Parenteral vitamin C (VitC) attenuated inflammation in murine sepsis models and in patients with sepsis. However information about the mechanisms by which VitC regulates these events is limited.

Methods: Humanized mice lacking VitC synthesis capability (Gulo^-/-) were used. VitC sufficient and deficient mice were challenged with sterile inflammation, or …

Chronic Behavioral And Cognitive Deficits In A Rat Survival Model Of Organophosphate Toxicity, Beverly Huang

Theses and Dissertations

Organophosphates (OPs) are a major class of pesticides and nerve agents that elicit acute toxicity by inhibiting acetylcholinesterase (AChE), the enzyme responsible for the degradation of the neurotransmitter acetylcholine in the central and peripheral nervous systems. Acetylcholine accumulation following extensive AChE inhibition leads to an acute cholinergic syndrome characterized by autonomic dysfunction, involuntary movements, muscle fasciculations, respiratory distress, and seizures. Despite their classification as moderate to highly toxic, OP pesticides are the most widely used class of insecticides in the U.S., and are even more commonly used worldwide. Additionally, there is a growing concern that OP nerve agents could be …