Medicine and Health Sciences Commons^™

Characterization Of Potential Interactions Between Transferrin Binding Proteins In Neisseria Gonorrhoeae, Shreni Mistry

Theses and Dissertations

Neisseria gonorrhoeae requires iron for survival and establishment of infection in the human host. Pathogenic Neisseriae have evolved a repertoire of high-affinity iron acquisition systems to facilitate iron uptake in the human host. This requires specific outer membrane receptors and energy-harnessing cytoplasmic membrane proteins. The transferrin receptor proteins of Neisseria gonorrhoeae are necessary for iron uptake from transferrin in the host. The iron uptake system consists of two transferrin binding proteins, (Tbp) A and B. TbpA is an integral outer membrane, TonB-dependent transporter that forms the pore for iron internalization. TbpB is a surface exposed lipoprotein that makes the iron …

Impacts Of Black Box Warning, National Coverage Determination, And Risk Evaluation And Mitigation Strategies On The Inpatient On-Label And Off-Label Use Of Erythropoiesis-Stimulating Agents, Arpamas Seetasith

Theses and Dissertations

Background: FDA black box warning, Risk Evaluation and Mitigation Strategies (REMS), and CMS national coverage determination (NCD) aim to reduce inappropriate use of erythropoiesis-stimulating agents (ESAs) that are widely used in anemic patients. Previous studies have not linked specific safety interventions to changes in ESA utilization patterns in the inpatient settings nor assessed such interventions on off-label use of the drugs. Ineffectiveness of the intervention and lag time between such interventions and the observed change in clinical practice could lead to serious clinical outcomes. In addition, such interventions may unintentionally reduce on-label and some off-label use of ESAs considered “appropriate” …

Design, Syntheses, And Biological Evaluation Of 14-N-Substituted Naltrexone Derivatives As Opioid Receptor Ligands, Orgil Elbegdorj

Theses and Dissertations

Opium, the dried resin obtained from the unripe seedpods of the poppy flower, has been used for medicinal and euphoric purposes since ancient times. Morphine, the main active ingredient of opium, and other clinically useful opioid analgesics all mediate their effects through activating the mu opioid receptor. Studies involving the mu opioid receptor knockout mice showed that the interaction with the mu opioid receptor is also responsible for many notorious side effects associated with these drugs including dependence and addiction. Therefore, selective antagonists for the mu opioid receptor are needed to study its function in drug abuse and addiction. Previously, …

Klf2 Is Required For Normal Mouse Cardiovascular Development, Aditi Raghunath Chiplunkar

Theses and Dissertations

Krüppel-like factor 2 (KLF2) is expressed in endothelial cells in the developing heart, particularly in areas of high shear stress, such as the atrioventricular (AV) canal. KLF2 ablation leads to myocardial thinning, high output cardiac failure and death by mouse embryonic day 14.5 (E14.5) in a mixed genetic background. This work identifies an earlier and more fundamental role for KLF2 in mouse cardiac development in FVB/N mice. FVB/N KLF2-/- embryos die earlier, by E11.5. E9.5 FVB/N KLF2-/- hearts have multiple, disorganized cell layers lining the AV cushions, the primordia of the AV valves, rather than the normal single layer. By …

Defining A Simplified Pharmacophore For Simocyclinone D8 Inhibition Of Dna Gyrase, Lauren Gaskell

Theses and Dissertations

The type II topoisomerase subfamily of enzymes has been clinically targeted by the widely used, broad-spectrum quinolone class of antibacterials. Due to emerging drug-resistant strains of bacteria, the quinolones’ effectiveness is threatened. The natural product simocyclinone D8 (SD8) has shown the ability to inhibit the type II topoisomerase, DNA gyrase, even when mutated to be resistant to the quinolones. In order to determine the pharmacophore required for SD8 binding to DNA gyrase, 16 compounds were synthesized. These compounds were then tested by surface plasmon resonance for their ability to inhibit the DNA – DNA gyrase binding interaction. It was found …

Patient Understanding Of Coordinated Medical Treatment Success Within The Minnesota Medical Home Model: An Exploratory Qualitative Inquiry, Jeremy F. Stockinger

Theses and Dissertations

The US health care system is often described as a complex, fragmented system where patients experience less access, coordinated, and comprehensive care that is ultimately more costly (Rosenberg, 2009). The problem addressed in this study was to understand coordinated medical treatment in the medical home model from the patient perspective. This study provides the opportunity to increase the understanding of the factors affecting coordinated medical treatment success.

Illness-Related Diabetes Social Support And Glycemic Control Among Middle Aged And Older Adults, Favel Leah Mondesir

Theses and Dissertations

Objective

The objective of this study is to investigate the association between illness-related diabetes social support (IRDSS) and glycemic control (GC) among a racially diverse sample of middle aged and older adults. In gender-stratified models we examine whether the relationship between IRDSS and GC is modified by race/ethnicity. Additionally, we explore the association between eight individual types of IRDSS and GC.

Methods

We used the Health and Retirement Study (HRS) 2002 and the 2003 Diabetes Survey. The final analytic sample consisted of 914 study respondents. Gender-stratified multivariable logistic regression models were used to calculate odd ratios (ORs) and 95% confidence …

Fishing And Fish Consumption Patterns In The Gullah/Geechee Sea Island Population, Jamelle Heyward Ellis

Theses and Dissertations

The Gullah/Geechee (G/G) people are descendants of West African slaves who remained in seclusion on the Sea Islands of South Carolina, North Carolina, Georgia, and Florida until the end of the Civil War in 1865. In addition to retaining their unique cultural language, they also remain largely a fishing subsistence population. Decades of urban development have reduced the G/G population's access to traditional fishing locations and have increased exposures to environmental contaminants in some bodies of water that are frequently fished by the G/G. Approximately 98.4% of SC rivers and streams and 77.6% of lakes have been assessed for aquatic …

Development And Validation Of A Predictive Model Of Return-To-Work Outcomes Of Injured Employees In Minnesota, A. Bentley Hankins

Theses and Dissertations

In Minnesota’s workers’ compensation system, injured employees at risk for sustaining permanent disability may be eligible for receipt of vocational rehabilitation (VR) services if they are determined to be capable of benefitting from such services. VR services can be a valuable resource to injured employees who need assistance minimizing their work disability and maximizing their residual wage-earning capacity. However, for VR services to be effective at a system level, it is necessary to precisely and accurately identify an injured employee’s rehabilitation potential. Failure to do so is likely to result in the misallocation of a scarce and costly resource. Given …

Role Of Microrna-155 In A Mouse Model Of Colon Cancer., Claire Mitchell Midyette

Theses and Dissertations

Colorectal cancer remains the third most common malignancy and the fourth most common cause of cancer mortality worldwide. Dysregulated miRNA levels are associated with several types of malignancies and may serve as important biomarkers and/or therapeutic targets in colorectal cancer. We examined the role of miRNA-155 on tumorigenesis and associated symptoms using a well-characterized mouse model of colorectal cancer. C57BL/6 wild-type mice and miRNA-155-/- mice (n=7-13 group) were given a single injection of AOM (10mg/Kg) followed by 3 cycles of DSS (2% in the water for 1 week followed by 2 weeks of plain water). A C57BL/6 wild-type group that …

A Critical Review Of Endometriosis Pathology, Brittany Lauren Cureton

Theses and Dissertations

Endometriosis is a complex, multifactorial, reproductive disorder present in approximately 10-15% of adult women between the ages of 25-35. This disorder occurs when endometrial glands and stroma grow ectopically on the surface of the ovaries, pelvic peritoneum, fallopian tubes, and the uterus. Endometriosis causes varying degrees of painful symptoms and infertility in infected individuals. Three main theories of endometrial accumulation attempt to explain the etiology of this elusive disease. There have been various staging of endometriosis symptoms that attempt to standardize classification as well as predict pain and infertility. Angiogenesis, necessary to the survival of endometrial tissue, along with immune …

Best Practice Guideline For Managing Interstitial Cystitis In Adult Women, Amanda Thomas Langford

Theses and Dissertations

Interstitial cystitis/painful bladder syndrome (IC/PBS) is a chronic disease characterized by symptoms of urinary urgency, frequency, bladder pain, and chronic pelvic pain in the absence of known pathology. Selection of appropriate treatments depended on the severity of the patient's symptoms and patient's preference. This review found that it is important for providers and patients to set realistic goals for symptom improvement when starting a new treatment.

The purposes of this project was to 1) conduct a substantive literature review on treatment guidelines for IC/PBS, 2) analyze the literature for comparing oral pharmacological interventions and behavioral interventions for IC/PBS, and 3) …

Assessment Of The Effectiveness Of An Innovative Screening Colonoscopy Protocol In Producing High Quality Performance And Outcomes By Trained Primary Care Physicians, Yi Jhen Li

Theses and Dissertations

Colorectal cancer (CRC) is the 3rd most prevalent cancer and 2nd leading cause of cancer death in the U.S. Colonoscopies have been recommended as the preferred screening method to prevent cancer by removing polyps before they transform into cancer. Although colonoscopy every 10 years is considered to be the preferred screening method, it is not perfect mainly owing to the variable quality of screening colonoscopy under community-based practice conditions. Although the effectiveness of colonoscopy in preventing CRC is documented, screening colonoscopy coverage in the US population remains low. This is partly due to low colonoscopy capacity due to a shortage …

Associations Between The Perceived And Built Food Environment, Timothy L. Barnes

Theses and Dissertations

Neighborhood food environments have been associated with dietary intake and obesity. Measures of the food environment have typically been characterized with geographic information systems (GIS)-based measures, however, the use of perception-based measures of the food environment have increased in frequency. Few studies have fully examined the relationship between perceptions and GIS-based measures of the food environment, especially considering the congruency between perceived and GIS-based presence of specific retail food outlets, nor the relationship between food outlets and perceived availability of healthy foods or fast food opportunities.

Telephone survey data from 705 residents in an eight-county region of South Carolina were …

Evaluation Of Mass Media Campaigns To Change Smokers' Knowledge, Attitudes, And Behaviors In China And Taiwan, Li-Ling Huang

Theses and Dissertations

Research in high income countries (HICs) suggest that anti-smoking television advertisements are most effective if they contain emotionally evocative graphic messages or personal testimonials that depict serious consequences from smoking. The ability to effectively translate these messaging strategies to low- and middle-income (LMICs) countries outside of Western cultures remains understudied. It is critical to determine which smoking cessation messages work best in LMICs because they increasingly bear the global burden of tobacco-related disease. To date there is limited evidence on the efficacy of tobacco control mass media campaigns and the relative effectiveness of different tobacco control messaging strategies in China …

Examining The Role Of Electronic Medical Record Generated Provider Reminders On Provider Offering Of Breast Cancer Screening Services, Charles Beverley, Jr.

Theses and Dissertations

Introduction:Breast cancer affects the lives of millions of women each year in the United States. Early detection by mammography screening can reduce the risk for advanced stages of breast cancer and improve the probability of long-term survival in women. Electronic medical records (EMRs) have been identified as a successful approach for increasing the offering of preventive care in breast cancer. This study examines the impact of EMR usage, and EMR generated provider reminders on physician ordering or providing of mammography screenings.

Methods:This study used survey data from the 2008-2010 National Ambulatory Medical Care Survey (NAMCS). Our sample included non-federal office-based …

Elucidation Of Mechanisms Generating 5-Hydroxymethylcytosine (5hmc) In Mammalian Mitochondria, Prashant Thakkar

Theses and Dissertations

DNA methylation plays a pivotal role in governing cellular processes including genomic imprinting, gene expression, and development. Recently, the Tet family of methylcytosine dioxygenases(Tet1, Tet2 and Tet3) was found to catalyze the oxidation of 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC), an intermediate in the pathway of DNA demethylation. Tet enzymes catalyze this hydroxylation in a 2-oxoglutarate and Fe2+ dependent manner. We have recently reported significant levels of 5mC and 5hmC modification in immunoprecipitates of mammalian mitochondrial DNA(mtDNA). We provide the first evidence that a DNA Methyltransferase-1 isoform (mtDNMT1) translocates to the mitochondria using an N-terminal mitochondrial targeting sequence. mtDNMT1 expression is …

The Role Of The Nucleosome Remodeling And Histone Deacetylase (Nurd) Complex In Fetal Γ-Globin Expression, Maria Amaya

Theses and Dissertations

An understanding of the human fetal to adult hemoglobin switch offers the potential to ameliorate β-type globin gene disorders such as sickle cell anemia and β-thalassemia through activation of the fetal γ-globin gene. Chromatin modifying complexes, including MBD2-NuRD and GATA-1/FOG-1/NuRD play a role in γ-globin gene silencing, and Mi2β (CHD4) is a critical component of NuRD complexes. In the studies presented in Chapter 2, we observed that the absence of MBD2 in a sickle cell mouse model leads to a decrease in the number of sickled cells observed in the peripheral blood, and significantly increases survival in these mice. Although …

Assessment Of The Feasibility Of Co-Administration Of Phenolic Dietary Compounds With Phenylephrine To Increase Its Bioavailability, Zhenxian Zhang

Theses and Dissertations

R-(-)-Phenylephrine (PE) is the most commonly used nonprescription oral nasal decongestant in the United States. It is a selective α1-adrenergic receptor agonist and has many years of safe usage. However, the efficacy of PE is controversial, due to its extensive pre-systemic metabolism, which leads to low and variable oral bioavailability (38 ± 9%, mean ± SD). Sulfation plays a very important role in pre-systemic metabolism of PE. The sulfation of PE occurs at its phenolic group, which is the preferred structural feature of many sulfotransferase (SULT) substrates. Compounds with phenolic groups have similar structures to PE, which may share the …

In-Vitro Pk/Pd Profiling And Modeling Of The Anti-Sickling Agents, 5-Hydroxymethyl Furfural (5-Hmf) And Novel Synthetic Allosteric Effectors Of Hemoglobin (Aeh) In Human Whole Blood, Apurvasena Parikh

Theses and Dissertations

Introduction. 5-HMF and novel INN-compounds are left-shifting AEH, shown to have anti-sickling action by forming transiently covalent Schiff-base adducts with hemoglobin (Hb), thereby increasing the Hb O2-affinity. They are hypothesized to be substrates for aldehyde dehydrogenase (ALDH) in the liver and red blood cells (RBC). Methods. Biopharmaceutical assessments were made for AEH, using calculated physicochemical properties. Their in-vitro hepatic metabolism (mediated by ALDH) was characterized using hepatic cytosol, and in-vitro-in-vivo extrapolations (IVIVE) were made. Inter-species differences in hepatic cytosolic ALDH activity were investigated using acetaldehyde as a model substrate in different mammalian species. Time- and concentration-dependent in-vitro disposition of 5-HMF …

Thc-Mediated Induction Of Δfosb And Its Modulation Of Cb1r Signaling And Adaptation, Lazenka Matthew

Theses and Dissertations

The main psychoactive and therapeutic effects of Δ9-tetrahydrocannabinol (THC) are mediated through cannabinoid type 1 receptors (CB1Rs). The therapeutic uses of THC are mitigated by the development of tolerance to these therapeutic effects, whereas tolerance does not readily develop to some of the side-effects of THC, like motor impairment and reward. The development of tolerance occurs through adaptations at CB1Rs, which include desensitization (G-protein uncoupling) and downregulation (receptor degradation). Brain region-dependent differences in THC-mediated adaptations are proposed to explain the differences in tolerance to various THC-mediated effects. These studies focused on whether ΔFosB, a stable transcription factor, could regulate CB1R …

Examining The Relationships Between Religiosity, Spirituality, Internalized Homonegativity, And Sexual Risk Behaviors Among African-American Men Who Have Sex With Men: The Sexual Health In Faith Traditions (Shift) Study, Stacy Whichard Smallwood

Theses and Dissertations

Background: African-American men who have sex with men (AAMSM) are at disproportionate risk for HIV infection. Although the disparities in infection rates between AAMSM and MSM of other groups have been well-documented, little is known about the factors that contribute to the disparity, particularly psychosocial factors. One such factor, internalized homonegativity (IH), has been identified as a potential predictor of AAMSM engagement in risky sexual behaviors. However, little has been known about the ways in which IH manifests itself in the lives of AAMSM, or the role that sociocultural institutions, such as African-American faith communities, play in the development of …

A Preliminary Study Exploring Racial Differences In Triage, Hospitalization Status, And Discharge Medication In An Emergency Department In Graniteville, Sc, Clare Pollock

Theses and Dissertations

Purpose

This study seeks to identify any racial differences present in assigned triage scores, hospitalization status and discharge medications in a rural hospital likely experiencing a surge after a mass casualty incident involving chlorine gas as a result of a train derailment. Differences were examined between Non-Hispanic White and African American adults who were moderately ill and who presented to the emergency department of the closest hospital to the accident site within 24 hours of the incident.

Methods

Non-Hispanic White and African American adults who presented to the emergency department of the closest hospital to the accident site and who …

Understanding The Early Stages Of Development Of A Global Health Partnership, Wendy Raquel Gonzalez Navarrete

Theses and Dissertations

Maternal and child undernutrition contributes to more than one-third of child deaths. Global Health Partnerships (GHP) have emerged as a response to undernutrition and other pressing health problems. GHPs promote joint decision-making among donors, multilateral agencies, and country partners. Despite their positive impact on health problems, GHPs have generated unintended negative effects on country partners. This study aimed to understand the factors, strategies, and processes conducive to the establishment of an effective GHP in the context of a cooperative regional effort to reduce undernutrition and improve maternal and child health in eight countries in Latin America, Regional Health Initiative (RHI). …

Association Between Concomitant Use Of Bisphosphonates And Serotonin Reuptake Inhibitors And Increased Risk Of Osteoporotic-Related Fractures: Among Community-Dwelling Postmenopausal Women, Abner Nyandege

Theses and Dissertations

Osteoporosis and depression are prevalent among older postmenopausal women 65 years or older. Bisphosphonates (BPs) and selective serotonin reuptake inhibitors (SSRIs) or serotonin norepinephrine reuptake inhibitors (SNRIs) are commonly used medications to treat these conditions. Inhibitory effects of BPs on osteoclasts are responsible for the reduction in fracture risk. SSRIs, however, are associated with increased fracture risk through decreasing osteoblasts and increasing osteoclastic activity. These effects of SSRIs could attenuate the beneficial effects of BPs. This dissertation describes the concomitant use of BPs and SSRIs among postmeopausa women and reports findings from examining the association between concomitant use of BPs …

Impact Of Physical Activity In The Prevention Of Colorectal Cancer, Sarah Ashley Barnes

Theses and Dissertations

This review evaluates the current understanding of research on the impact of physical activity in the prevention of colorectal cancer. Current biological mechanisms implicated in physical activity and colorectal cancer risk reduction are blood glucose regulation, insulin sensitivity, leptin and adiponectin profiles, inflammation as well as secreted protein acidic and rich in cysteine (SPARC), an exercise induced myokine. Recent literature indicates that 30-60 minutes of moderate to vigorous activity a day is effective against colorectal cancer development, and there is convincing evidence of aerobic exercise as differently beneficial in recruiting mechanisms identified as preventative against colorectal cancer. This article provides …

Resveratrol Attenuates The Development Of Trans-Aortic Constriction (Tac) Induced Heart Failure In Mice, Prakash Kumar Gupta

Theses and Dissertations

Heart failure (HF) still remains the leading cause of morbidity and mortality and imposes severe global affliction and enormous cost on the healthcare system. Although current pharmacological therapies have shown to slow down the progression of HF, but seems to have reached their limits in improving overall patient prognosis. Thus, an immediate call for novel alternate therapies are needed which act independently as well as in conjunction with current treatment modality. Studies were performed in the well-established transverse aortic constriction (TAC) model of chronic pressure overload (PO) in mice. In the first series of studies, Male C57BL6 mice (26-28 g) …

Linking Obesity To Colorectal Cancer: Recent Insights Into Plausible Biological Mechanisms, Catherine Guffey

Theses and Dissertations

Obesity has emerged as a leading environmental risk factor for the development of CRC. However, the mechanisms underlying this relationship have not yet been fully explained. Recent literature has focused on 1) inflammatory processes, 2) adipokines, and 3) estrogen. Obesity-enhanced inflammation is largely orchestrated by increases in adipose tissue macrophages leading to the secretion of TNF-alpha, MCP-1, and IL-6, all of which are linked to CRC. Adiponectin is decreased with obesity and has been reported to be negatively associated with CRC, while leptin, which is increased, is positively associated with the disease. Estrogen has been shown to influence CRC, although …

Bioassay Guided Fractionation Of American Ginseng. A Hexane Fraction Of American Ginseng Suppresses Colitis And Associated Colon Cancer. Mechanism Of Action., Deepak Poudyal

Theses and Dissertations

Inflammatory Bowel Disease (IBD) [Ulcerative colitis (UC) and Crohn's Disease (CD)] is a group of chronic disorders of unknown etiology characterized by inflammation in the gastrointestinal tract associated with a high colon cancer risk. UC is characterized by periods of active disease ("flare-ups"), followed by periods when the disease is inactive ("remission"). The end result is an abnormal immune response with repeated episodes of colonic inflammation. Conventional treatment of UC by aminosalicylates, TNFα inhibitors, and steroids have modest effects, and come with a high risk of side effects including dyspeptic symptoms, gastric ulceration and sometimes hospitalization and deaths. Because of …

Insects As Indicators Of Environmental Stress, De Anna Estella Beasley

Theses and Dissertations

In the face of climate change-related events and anthropogenic disturbances, understanding the impacts of these events on species richness, abundance and distribution is important for us to mitigate biodiversity loss and better predict consequences for the environment and for human life. Insects are excellent models for understanding the consequences of environmental stress due to the sensitivity of their development and behavior. The overall focus of my dissertation research is the investigation of fluctuating asymmetry and oviposition behavior as indicators of environmental stress. My research includes a meta-analysis of published literature, and empirical research that was part of a collaborative initiative …