Medicine and Health Sciences Commons^™

Social Support, Weight Loss Attempts And Satisfaction, Allison Drew

Theses and Dissertations

Objective: The purpose of this study was to determine the extent to which the presence of social support correlates with attempts at weight loss in the past 12 months, attempts not to gain weight in the past 12 months, and participants’ satisfaction with their weight status. Methods: We used a cross-sectional study design using data collected by the 2003-2004 and 2005-2006 National Health and Nutrition Examination Surveys (NHANES) (CDC). For this study we included males and females, of multiple ethnicities, and a range of ages from 40 to 70 + years. Participants with missing data on height and weight were …

Effect Of Metro Living On Oral Cancers In Virginia: 2001-2005, Preeti Sastry

Theses and Dissertations

Background: Forty percent of all head and neck cancers occur in the oral cavity. According to ICD-O (International classification of diseases for oncology) C00-C14 includes cancers of the lip, oral cavity and pharynx. Studies have indicated that increased population density or Metro living have increased oral cancer incidence. The objectives of this study are to look at the distribution of Oral and Oro pharyngeal Cancers in Virginia from 2001-2005 The study aims to determine if there is an association between metro living (beale code 3) and advanced Oral Cancers. This study is also being done to determine if Metro living …

Medicare Managed Care Penetration And Prevalence Of Older Adult Disability, Christine Moe

Theses and Dissertations

OBJECTIVE: To investigate the relationship between Medicare Managed Care (MMC) penetration and percentage of disability in older adults (individuals age 65 and older). Considering disability as an indicator of one or more unsuccessfully managed chronic diseases, this study investigates the assumption that managed care improves coordination of care, as well as access to preventive care. If managed care’s mandate is being met, then it should be evidenced in decreased prevalence of older adult disability. METHOD: Taking an ecological approach, this study used data from the Agency for Healthcare Research and Quality (AHRQ, 2003) to compare the percentage of older adult …

Season Of Birth And Risk For Schizophrenia, Seth Roberts

Theses and Dissertations

Background: Schizophrenia is a chronic, debilitating mental disorder characterized by positive (e.g., hallucinations, delusions) and negative (e.g., catatonia, flat affect) signs and symptoms. Many studies suggest that individuals born in winter or spring months are at increased risk for schizophrenia. Study Objectives: 1) To determine whether season of birth affects risk for schizophrenia in the Irish Study of High Density Schizophrenia Families (ISHDSF). 2) To examine, by computer simulation, power to detect genetic associations with schizophrenia under a variety of conditions and using different analytic strategies. 3) To test whether specific genes are associated with schizophrenia in the Irish Case …

Do Black Msm Have More Idu And Hiv Positive Partners Compared To White Men Having Sex With Men ?, Shankar Krishnappa

Theses and Dissertations

Objectives: This study estimates the proportion of intravenous drug use (IDU) partners and HIV positive sexual partners among black and white and examine the association between repeat HIV testing and sex with high risk partners. Methods: A cross-sectional study of MSM was conducted by using pooled data from counseling, Testing, Referral services in Virginia, USA 2002-2007. Results: We obtained a sample of 19679 MSM out of which 10924(56%) and 6739(34%) were white and black MSM respectively. The proportion of IDU partners and HIV positive partners were among white MSM (5% and 11%) and black MSM (3% and 9%) respectively. Age …

Fetal And Early Neonatal Death: Do The Determinants Vary?, Ashley Carter

Theses and Dissertations

Purpose: To compare the determinants and distribution of fetal and early neonatal deaths in the Commonwealth of Virginia. Background: Much attention is devoted to reducing the infant mortality rate which was declining up until 2002. The recent rise was parsed and found to stem from an increase in deaths during the early neonatal period. Fetal deaths are not well understood and are not routinely included when evaluating infant mortality. Methods: Using data collected from 2001 to 2006 fetal death and linked infant birth and death certificates by the Virginia Department of Health, crude mortality rates and leading causes of death …

Creation Of A Mouse With A Humanized Fpgs Gene Compatible With Normal Development, Linying Xie

Theses and Dissertations

Abstract: Folylpoly-γ-glutamate synthetase (FPGS) catalyzes the formation of polyglutamate forms of the reduced folates and antifolates such as methotrexate (MTX) and pemetrexed; this allows the retention of folates and antifolate cancer drugs inside the cell. The enzyme activity of FPGS is essential for cell proliferation and survival. The mouse fpgs gene contains two promoters spaced 10 kb apart which are activated in a tissue-specific manner. The upstream promoter (P1) and exons A1a and A1b are used in some differentiated tissues, mainly liver and kidney, whereas the downstream promoter (P2) and exon 1 are used in rapidly dividing cells. In contrast, …

In Vitro Models For Inhaled Corticosteroid (Ics) Aerosols: A Study Of Their Biopharmaceutics And Pharmacology, Deepika Arora

Theses and Dissertations

Lung cellular disposition and anti-inflammatory pharmacology of inhaled corticosteroids (ICSs) is complex, comprised of a cascade of aerosol deposition and dissolution, followed by cellular uptake for local pharmacological action. This project hypothesized that the kinetics of dissolution for certain ICS aerosols generated from inhaler products were kinetically rate-determined for their cellular uptake and local pharmacological action. A novel dissolution testing system was developed to determine the dissolution kinetics for the ICS aerosols. A total of 5 ICSs aerosols generated from 6 inhaler products were collected in 2.1-3.3 or 4.7-5.8 µm of aerodynamic diameters at 0.7-19.8 µg on filter membranes by …

The Expression And Function Of Phosphacan/Rptpβ In Adaptive Synaptogenesis After Traumatic Brain Injury, Janna Harris

Theses and Dissertations

Traumatic brain injury (TBI) affects 1.5 million Americans annually and is a major health concern. Increasing evidence suggests that the brain extracellular environment regulates plasticity and synaptic recovery following TBI. Here we have focused on phosphacan/RPTPβ, an alternatively spliced group of chondroitin sulfate proteoglycans which are prominent within the mature brain extracellular matrix (ECM). Previous studies show that phosphacan/RPTPβ influences neuronal migration, adhesion, neurite outgrowth, and morphogenesis. However, our understanding of how these important ECM components are involved in recovery from brain trauma remains unclear. In the present study, we used unilateral entorhinal cortex lesion (UEC), a model which induces …

Selective Non-Peptide Mu-Opioid Receptor Antagonist: Design, Synthesis And Biological Studies, Lindsey Aschenbach

Theses and Dissertations

There are currently many opioid agonists available for clinical use as analgesics. However, many of these opioid agonists have notorious side effects including respiratory depression and may lead to addiction and dependence. Problems associated with these opioid agonists are determined to come from their interactions with the mu-opioid receptor. Opioid antagonists, such as naltrexone, have shown to aid in the treatment of opioid addiction. Although naltrexone has high affinity to the mu-opioid receptor, it lacks selectivity. Novel selective mu-opioid receptor antagonists were designed based on the identification of important pharmacophore elements in several known mu-opioid receptor agonists and antagonists. These …

Discovery And Initial Characterizations Of Neurofascin 155 High And Neurofascin 155 Low, Anthony Pomicter

Theses and Dissertations

This thesis contains the findings from four years of research regarding an oligodendrocyte protein named neurofascin 155. The role of this protein in maintaining adhesion between the myelin sheath of oligodendrocytes and the axons of neurons has become well established in recent years and the research presented here has revealed that while western blots have previously shown one protein/band representing neurofascin 155, there are two proteins/bands. These two proteins have been named neurofascin 155 high and neurofascin 155 low due to their previous inclusion in the single band. The work leading up to their discovery, findings, and the relevance of …

Interneuron Subtypes Are Differentially Altered In Malformed, Epileptogenic Cortex, Amanda George

Theses and Dissertations

The propensity for seizures in patients with epilepsy is due to underlying cortical hyperexcitability, the mechanisms of which are poorly understood. Particularly difficult to treat are patients with developmental malformations of cortex. Using the freeze-lesion rat model of one such malformation, polymicrogyria, we identified, in lesioned cortex, alterations in specific interneuron subpopulations that may promote hyperexcitability. Previous studies demonstrate increased excitatory input to the paramicrogyral region. An increase in the frequency of spontaneous excitatory postsynaptic currents (sEPSCs) recorded from pyramidal cells has also been shown. We report an increase in sEPSCs recorded from one subtype of interneuron, the low threshold-spiking …

Analysis Of The Mechanism Of Transferrin-Iron Acquisition By Neisseria Gonorrhoeae, Noto Jennifer Mcmillan

Theses and Dissertations

Neisseria gonorrhoeae is an obligate human pathogen that requires iron for its survival within the host. N. gonorrhoeae expresses high-affinity iron acquisition systems to acquire iron from host iron binding proteins. The gonococcal transferrin-iron uptake system is composed of two transferrin binding proteins, TbpA and TbpB. TbpA is a TonB-dependent, outer membrane transporter, while TbpB is a surface-exposed lipoprotein. Unlike TbpA, TbpB is not required for transferrin utilization, but makes the process more efficient. The precise mechanism by which TbpA and TbpB function to mediate transferrin-iron uptake has not been fully characterized. However, the mechanism of iron acquisition from transferrin …

Identification Of Pharmacological And Molecular Mechanisms Involved In Nicotine Withdrawal, Kia Jackson

Theses and Dissertations

Tobacco dependence is the leading cause of preventable death in the United States. Despite currently available smoking cessation therapies, there is a high rate of relapse in smoking among those attempting to quit. While the somatic signs of nicotine withdrawal (insomnia, increased appetite, weight gain) contribute to the continuation of smoking behavior, it has been hypothesized that the affective signs (depression, anxiety, craving, irritability) are greater motivators of relapse and continued tobacco use. There are few studies that assess the molecular and receptor-mediated mechanisms of nicotine withdrawal; therefore, our studies focus on identifying the nicotinic acetylcholine receptor (nAChR) subtypes and …

Identification Of Virulence Determinants For Streptococcus Sanguinis Infective Endocarditis, Lauren Turner

Theses and Dissertations

Streptococcus sanguinis is the second most common causative agent of bacterial infective endocarditis (IE). Risk of S. sanguinis IE is dependent on pre-disposing damage to the heart valve endothelium, which results in deposition of clotting factors for formation of a sterile thrombus (referred to as vegetation). Despite medical advances, high mortality and morbidity rates persist. Molecular characterization of S. sanguinis virulence determinants may enable development of prevention methods. In a previous screen for S. sanguinis virulence determinants by signature-tagged mutagenesis (STM) an attenuated mutant was identified with a transposon insertion in the nrdD gene, encoding an anaerobic ribonucleotide reductase. Evaluation …

The Relationship Between Perceived Personal Risk Of Getting Prostate Cancer And Prostate-Specific Antigen (Psa) Screening, Yeatoe G. Mcintosh

Theses and Dissertations

Abstract Title: The Relationship between Perceived Personal Risk of getting Prostate cancer and Prostate-Specific Antigen (PSA) Screening Yeatoe G. McIntosh, MPH Candidate Advisor: Emmanuel Anum, MBChB, MPH, PHD Preceptor: Emmanuel Anum, MBChB, MPH, PHD Background: Prostate cancer is one of the most common cancer diagnoses in the United States. The American Cancer Society estimates that in 2008 28,660 deaths would be attributed to prostate cancer, projecting it to be the leading cause of cancer deaths in U.S. men. Despite the potential threat this cancer presents to men and the potential for improved disease outcomes from early detection, guidelines for screening …

Modeling Pure Vasogenic Edema In The Rat Brain, Charles Nottingham

Theses and Dissertations

Targeted drug delivery to the brain is difficult to achieve using conventional techniques, largely due to the blood-brain barrier’s (BBB) impediment to drug diffusion into the brain parenchyma. In response, development of convection-enhanced delivery (CED) offers the ability to circumvent the BBB and target specific areas of the brain. Predictability of infusate movement in pathological brain states during CED will maximize the effectiveness of this treatment, and therefore modeling of infusate movement must be characterized. Previous work from our lab effectively modeled CED in rats using the middle carotid artery occlusion model of cytotoxic edema. However, previous models examined for …

Physiological And Molecular Characterization Of Genetic Competence In Streptococcus Sanguinis, Alejandro Rodriguez

Theses and Dissertations

The ability of bacteria to assimilate free DNA from the environment is known as competence. Though many studies have focused on competence regulation in Streptococcus pneumoniae and Streptococcus gordonii, Streptococcus sanguinis has yet to be examined. Physiological characterization of competence in S. sanguinis strain SK36 and its comC mutant, JFP41, led to the genome-wide transcriptional analysis of cells induced to competence via addition of competence-stimulating peptide (CSP). A total of 128 genes were induced at least 2-fold, 74 of which were classified as either “early” or “late” based on their induction patterns. Expression patterns were verified using qRT-PCR. This study …

Promotion Of Tumor Cell Death Through The Induction Of, Tuyen Nguyen

Theses and Dissertations

Microtubule poisons have proven to be effective in the treatment of a variety of malignancies. Although taxol-based derivatives promote microtubule stabilization, there is continuing interest in compounds that, like colchicines, act as microtubule destabilizing agents. Previous work from this laboratory showed that the novel microtubule poison, JG- 03-14, was active against breast tumor cells, promoting autophagic cell death. In the current work, we studied the influence of JG-03-14 on p53 wild type HCT116 colon carcinoma cells. A crystal violet sensitivity assay indicated that JG-03-14 induced growth inhibition, with 75% suppression of growth evident at a concentration of 500 nM. Time …

The Experience Of Volunteering For Hurricane Katrina Relief / Theoretical Explanations For Nurses’ Involvement As Volunteers In Global Disasters, Deborah Ulmer

Theses and Dissertations

This study is about the nature of nurses' decision making related to volunteering to provide humanitarian aid in a major national disaster. Additionally, it is about the lived experience of nurses who volunteered in that disaster. It is a transcendental phenomenological study using the approach of Clarke Moustakas and the purpose of the study was to describe the experiences of the nurses, their reasons for volunteering, and the impact of their experience on their lives several years later.

Effects Of Altered Superoxide Dismutase Expression On Age-Related Functional Declines And Survival In Drosophila, Ian Martin

Theses and Dissertations

Most organisms experience progressive declines in physiological function as they age. A number of studies in a variety of species support a strong link between oxidative damage, age-related functional declines and life span determination. Here, manipulating the expression levels of superoxide dismutase (SOD) isoenzymes SOD1 and SOD2, resulted in altered functional senescence and survival characteristics in Drosophila. Overexpression of cytosolic Sod1 using the yeast GAL4/UAS system conferred a 30-34% increase in mean life span and resulted in an attenuated senescence of odor avoidance behavior in aging flies. Tissue-specific Sod1 overexpression selectively in the nervous system or muscle failed to reproduce …

Electrical Behavior Of Non-Aqueous Formulations: Role Of Electrostatic Interactions In Pressurized Metered Dose Inhalers (Pmdis), Reshma Kotian

Theses and Dissertations

Aerosol electrostatics is an important property of pharmaceutical aerosols. The electrostatic properties of pMDI aerosols have been shown to be a function of both formulation and packaging components. The modified ELPI enables measurement of aerosol charge as a function of particle size, and the simultaneous determination of the mass distribution using chemical analysis. However, in order to fully assess the cause and effects of aerosol electrostatics in terms of its biological and regulatory implications, it is necessary to understand the basic charging mechanisms inside the pMDI formulation.

Electrical resistivity and zeta potential measurements confirmed the presence of charged species within …

Inflammatory Regulation Of Cysteine Cathepsins, Blaine Creasy

Theses and Dissertations

Cysteine cathepsins B, L and S are endosomal/lysosomal proteases that participate in numerous physiological systems. Cathepsin expression and activity are altered during various inflammatory diseases, including rheumatoid arthritis, atherosclerosis, neurodegenerative diseases and cancers. Early immune responses to microbial pathogens are mediated by pattern-recognition receptors, including Toll-like receptors (TLR). Signaling through TLR causes cell activation and release of inflammatory mediators, which can contribute to the severity of chronic inflammatory diseases. The impact of TLR cell activation on cathepsins B, L and S activities was investigated using live-cell enzymatic assays. Individual ligands of TLR4, TLR2 and TLR3 increased intracellular activities of the …

Contamination Of Dental Waterlines: Efficacy Of Seven Waterline Treatments And Three In-Office Bacteria Test Kits, Adam Davis

Theses and Dissertations

This study compared seven dental unit water line (DUWL) treatments and three in-office bacteria test kits. Sodium hypochlorite (NaOCl) 1:10 in tap water weekly; 3 drops of NaOCl in 1 liter of water; Dentapure® DP 40; ICX™ tablet; Sterilex® Ultra powder; Lines™; and Selective Micro® Dental-Clean. Traditional culture technique was compared to HPC Dental Sampler; Aquasafe™ Dental Unit Water Line Test Kit; and Bacteria in Water Test Kit. Eight dental units in the Virginia Commonwealth University Graduate Endodontic Clinic were randomly assigned treatment regimens. Samples were taken weekly initially and after flushing for 1 minute. In conclusion NaOCl hypochlorite 1:10 …

Designing Non-Saccharide Heparin/Heparan Sulfate Mimics, Arjun Raghuraman

Theses and Dissertations

Glycosaminoglycans (GAGs) are complex biopolymers that play important roles in inflammation, coagulation, angiogenesis, cell adhesion and viral invasion by interacting with several different proteins.1,2 Structurally, GAGs are built up of several different sulfated disaccharide units.3 Specific GAG sequences that uniquely recognize their cognate proteins exist. Such specificity typically arises from the binding of unique sulfation patterns on the linear GAG chain to highly electropositive protein domains. Thus, these highly charged, sulfated biopolymers potentially represent a new class of therapeutics. Yet, the major stumbling block to the development to these agents is their extremely complicated and tedious chemical synthesis. We hypothesized …

Nucleoplasmic And Cytoplasmic Degradation Of Telomerase: Implications Toward Telomerase-Based Cancer Therapy, Binh Nguyen

Theses and Dissertations

Telomerase is a ribonucleoprotein that is reactivated in cancer cells to allow for continuous cellular division and indefinite growth. With telomerase being expressed in more than 85% of all cancer, it is imperative that we understand how to selectively inactivate and degrade this unique DNA polymerase. In doing so, we can specifically target tumor cells to erode their telomeres so that they will undergo apoptosis or senescence. Through this research, we have learned that telomerase can be degraded in the nucleoplasm by Hsp90 chaperone inhibition and in the cytoplasm by the dominant negative mutant, D712A V713I. These findings should guide …

Assessment Of Seminary Education On End Of Life Issues, Stefan Hakon Pomrenke

Theses and Dissertations

Background: The US health care system faces increased costs from end of life (EOL) care. The intensive approach to EOL treatment with greater use of procedures in ICUs has led to decedent spending six times greater than that of survivors in the hospital. Experts in ICU and Palliative care fields have called for greater utilization of end of life planning and education. To date, EOL education has been dominated by the technologically driven medical field and the church has been under-utilized. The US population relies on clergy support for many mental health and EOL issues. Clergy report feeling uncomfortable in …

Quantifiying The Depth Of Oral Sedation Using Bispectral Index Monitoring, John Flowers

Theses and Dissertations

Purpose: To determine whether Bispectral Index Monitoring is an effective tool for quantifying sedation depth after the administration of oral drug regimens in children.Methods: This retrospective study reviewed the charts of 75 children who received oral conscious sedation for dental treatment. Data collected from the chart included; 1) BIS values at 5 minute intervals and at five critical events: pre-operative, local anesthesia delivery, rubber dam placement (if utilized), during operative treatment, and postoperatively, 2) behavior ratings at the five critical events and an overall behavior assessment, 3) treatment data, and 4) demographic data. Results: The mean BIS value for orally …

Enzymology And Molecular Biology Of Bile Acid 7alpha- And 7beta- Dehydroxylation By The Intestinal Bacteria Clostridium Scindens And Clostridium Hylemonae, Jason Michael Ridlon

Theses and Dissertations

The collective microbial genomes within our gut(microbiome) represent a powerful metabolic force, leading many authors to call our GI flora an "organ within an organ", and the metagenomic sequencing of our microbiome, "the second human genome project". Bile acids, endogenously produced by the host liver, represent both a strong selective pressure for potential colonizers, aswell as substrates for microbial metabolism. Indeed, microbes have evolved enzymes to deconjugate bile salts, epimerize bile acid hydroxyl groups, and 7alpha-dehydroxylateprimary bile acids. The products of microbial 7alpha-dehydroxylation, secondary bile acids, are suggested by numerous lines of evidence to be involved in promoting colon carcinogenesis. …

Endocannabinoid Modulation Of Spatial Memory In Aversively And Appetitively Motivated Barnes Maze Tasks, John Pinckney Harloe

Theses and Dissertations

Genetic deletion or pharmacological blockade of the CB1 receptor has been reported to impair extinction learning in aversive conditioning (i.e., conditioned fear and Morris water maze) paradigms, but not in operant procedures in which food reinforcement is earned. It is difficult to discern whether the differential effects caused by CB1 receptor disruption on extinction result from the hedonics (i.e., aversive vs. appetitive) or is related to the required responses associated with these disparate tasks. In order to evaluate whether the hedonics is the determining factor, we used either aversive (i.e., escape from bright lights and air turbulence) or appetitive (i.e., …