Medicine and Health Sciences Commons^™

The Role Of The Rx3/ Otx Pathway In Zebrafish Eye Development, Navaneetha Krishnan Bharathan

Theses and Dissertations

Colobomas are a type of eye defect characterized by the presence of a hole in certain eye structures. In this study, the roles of the zebrafish Otx genes, otx2 and otx1a, as well as the Rx family gene, rx3, in choroid fissure closure, the disruption of which leads to the onset of colobomas, were studied. It was observed that while the otx2 loss-of-function mutant, otx2hu3237 displayed small colobomas and the otx1a mutant, otx1a6del, did not exhibit any morphological eye defects, zebrafish possessing both mutations presented with a range of colobomas, some of which were more severe than otx2 single mutants …

Comprehensive Review On The Existence Of Genomic Imprinting In Aves, Derek Gygax

Theses and Dissertations

Genomic imprinting results in monoallelic parent-of-origin gene expression. Therian mammals show conclusive evidence for imprinting, while the evidence in Aves is conflicting. It’s unclear if Aves have the proteins necessary for establishment and maintenance of imprinting loci. Every examined avian orthologue to mammalian imprinted genes shows biallelic expression providing evidence for a lack of imprinting in Aves. While the known parent-of-origin quantitative trait loci in chicken do not overlap with differentiated methylated regions, further analysis with a larger sample size is required. No transcript in the chicken transcriptome at incubation day 4.5 shows parent-of-origin expression, providing strong evidence for a …

Characterization Of The Discriminative Stimulus Effects Of Nitrous Oxide, Kellianne J. Richardson

Theses and Dissertations

Nitrous oxide (N2O) is a widely used anesthetic adjunct in dentistry and medicine that is also commonly abused. N2O alters the function of several receptors in vitro and ex vivo, however, the receptors systems underlying its abuse-related intoxicating effects are poorly understood. The goals of this dissertation were to (1) establish N2O as a discriminative stimulus, (2) characterize the temporal properties of the discriminative stimulus, (3) determine the degree of similarity between N2O and other inhalants and (4) explore the neurochemical effects responsible for the stimulus properties of N2O. Twenty-four mice were trained to discriminate 10 minutes exposure to 60% …

Redox Triggering Of Podocyte Nlrp3 Inflammasomes And Glomerular Injury In Hyperhomocysteinemia, Justine M. Abais

Theses and Dissertations

Hyperhomocysteinemia (hHcys), an important pathogenic factor contributing to the progression of end-stage renal disease (ESRD), has been shown to activate NOD-like receptor protein 3 (NLRP3) inflammasomes and cause podocyte dysfunction and glomerular sclerosis. hHcys induces aggregation of the three inflammasome components – NLRP3, apoptosis-associated speck-like protein (ASC), and caspase-1 – and its activation is indicated by increased caspase-1 activity and secretion of interleukin-1β (IL-1β). The aims of the present study sought to elucidate the role of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase-mediated redox signaling in hHcys-induced NLRP3 inflammasome activation, to dissect the contribution of common endogenous reactive oxygen species (ROS) …

Examination Of The Communication Practices And Preferences Between Orthodontists And General Dentists, Kevin Bibona

Theses and Dissertations

The purposes of this study were to evaluate if orthodontists’ and general dentists’ perceptions of how often, under what circumstances, and by which media orthodontists communicated with general dentists were similar, and to determine if orthodontists were meeting the communication needs of general dentists. Orthodontists (N=1,000) and general dentists (N=1,000) throughout the United States were randomly selected to participate in a web-based and mailed survey, respectively. The results indicated that the orthodontists communicated with general dentists using the type of media the general dentists preferred to use. As treatment complexity increased, orthodontists shifted from one-way forms of communication to two-way …

Patient Discomfort In The Icu: Ett Movement Effects, Virginia Hamilton

Theses and Dissertations

Critically ill patients who require MV are at risk for a number of complications, including the development of ventilator-associated events (VAE) and agitation that may require the use of sedation. Patients experience anxiety and discomfort during mechanical ventilation from a variety of sources including unfamiliar breathing assistance and an inability to communicate anxiety and pain verbally, but a primary cause of discomfort identified by these patients is the simply the presence of the endotracheal tube (ETT). Discomfort often leads to agitation and may be exacerbated by ETT movement. Management of agitation typically involves the use of sedative therapy and has …

Using Cbct As A Diagnostic Tool For Evaluation Of Infrabony Defects In Vivo, Anya Rost

Theses and Dissertations

BACKGROUND: Clinicians rely on radiographs and clinical exam to assess infrabony defects. However, two-dimensional radiographs have many limitations. Three-dimensional imaging has shown promise and has provided more precise measurements of defects created in skulls. The aim of this study is to compare the diagnostic efficacy of cone beam computed tomography to clinical measurements in patients presenting with infrabony defects. METHODS: The study population included 20 patients with 25 infrabony defects. Clinical measurements of pocket depth (PD), gingival margin (GM), bone sounding (BS) were obtained and PD and BS were compared to CBCT measurements. RESULTS: The average difference between the means …

More Than Just Hospitals: An Examination Of Cluster Components And Configurations, Patrick Shay

Theses and Dissertations

Over the past 25 years, health care organization scholars have observed the dramatic emergence of hospital-based clusters in local markets throughout the U.S. These important organizational forms require same-system ownership of multiple general, acute care hospitals operating within a single local market, and as such they include multi-hospital systems that are entirely contained in a single urban market as well as clustered extensions or subsystems of larger regional and national systems. However, despite their noted growth as powerful forces in local markets, relatively few studies have examined these clusters, and as a result there remains a significant gap in our …

Evaluation Of Maxillary Molar Furcations, Clinical Measurements Versus Cone Beam Computed Tomography, Jessica Allen

Theses and Dissertations

BACKGROUND: The use of three-dimensional imaging has shown to provide advantages to the clinician in assessing bone morphology. The aim of this study will be to compare the diagnostic efficacy of cone beam computed tomography (CBCT) versus diagnostic clinical measurements in patients presenting with furcation involved maxillary first molars. METHODS: The study population included 20 patients with 34 maxillary first molar teeth with furcation involvement. Clinical horizontal and vertical probing measurements were compared to CBCT measurements taken by two calibrated examiners. RESULTS: Horizontal measurements showed a significant difference between Glickman class II and class III. There were no statistical significant …

An Examination Of The Relationship Of Abo Blood Group And Lifespan In A Hospitalized Population In The Southeastern United States, Tara Moon

Theses and Dissertations

The clinical significance of ABO blood group is evident and universally accepted with regards to blood transfusion and pregnancy; however, the importance of ABO blood group as it relates to other diseases or disorders and overall mortality is not fully understood by the scientific community. Many studies have suggested associations between blood groups and disease, but consensus has not been reached regarding overall survival or longevity. This epidemiological, retrospective review of ABO blood group and age at the time of death in a hospitalized population in the Southeastern United States is the first multi-site study to examine this relationship. The …

Community-Dwelling Older Adults' Adherence To Fall Prevention Recommendations, Suzänne Fleming Taylor

Theses and Dissertations

Falling among older adults is a leading cause of concern due to the known impacts including physical injury, loss of independence, increased health care costs, and mortality. In efforts to decrease the numbers of falls experienced by older adults, healthcare providers assess individuals’ fall risks and provide corresponding fall prevention recommendations. The effectiveness however, of these recommendations, is only as strong as the level of adherence to those recommendations; which has proven low in recent research. Using the theoretical foundation of the Health Belief Model, this study quantified adherence to environmental fall prevention recommendations. Twenty-two community-dwelling older adults participated in …

An Evaluation Of Prenatal Care Clinic Selection And The Association With Subsequent Process/Outcome Measures Among Medicaid Beneficiaries, Lynn Vanderwielen

Theses and Dissertations

In 2010 Medicaid financed approximately 48% of all births in the United States and nearly 30% of all births in Virginia. Due to strict state-specific eligibility criteria, many low-income women qualify for Medicaid coverage exclusively as a result of pregnancy status. As the nation moves forward with the Patient Protection and Affordable Care Act (PPACA), state-elected Medicaid expansion has the potential to expand services to women of reproductive age that would precede pregnancy events and offer continuous access to care postpartum. Despite this potential influx of newly insured women, little is known about how this population may make decisions regarding …

The Role Of P2x Receptors In Hiv And Opiate-Related Neurotoxicity, Mary Sorrell

Theses and Dissertations

Emerging evidence suggests that opioid drugs can exacerbate neuroAIDS. Microglia are the principal neuroimmune effectors thought to be responsible for neuron damage in HIV-infected individuals, and evidence suggests that drugs acting via opioid receptors in microglia aggravate the neuropathophysiological effects of HIV. The P2X family of ATP activated ligand-gated ion channels regulates key aspects of microglial function. In addition, opioid-dependent microglial activation has been reported to be mediated through P2X4 signaling, prompting us to investigate P2X receptors contribution to the neurotoxic effects of HIV and morphine. In vitro experiments showed treatment with TNP-ATP prevented the neurotoxic effects of morphine and/or …

Multi – Modality Molecular Imaging Of Adoptive Immune Cell Therapy In Breast Cancer, Fatma Youniss

Theses and Dissertations

Cancer treatment by adoptive immune cell therapy (AIT) is a form of immunotherapy that relies on the in vitro activation and/or expansion of immune cells. In this approach, immune cells, particularly CD8+ T lymphocytes, can potentially be harvested from a tumor-bearing patient, then activated and/or expanded in vitro in the presence of cytokines and other growth factors, and then transferred back into the same patient to induce tumor regression. AIT allows the in vitro generation and activation of T-lymphocytes away from the immunosuppressive tumor microenvironment, thereby providing optimum conditions for potent anti-tumor activity. The overall objective of this study is …

Behavioral Assessment And Hplc/Ms/Ms Identification Of The Synthetic Cannabinoid, Cp47,497, In Mice, Kimberly L. Samano

Theses and Dissertations

CP47,497 and other synthetic cannabinoid compounds were incipiently synthesized as research tools to investigate the mechanisms by which marijuana affects the brain and to aid in the development of therapeutic agents. Recently, these cannabinoid compounds have resurfaced in the designer drug market, marketed as “herbal incense products” (HIPs). Their popular use has resulted in an alarming rate of reported adverse effects and toxicities. Current legislation classified CP47,497 and several other synthetic cannabinoids compounds as Schedule I agents, but abuse of these compounds persists with serious consequences to public health and safety. In vivo studies examining the behavioral consequences of abused …

Access To Therapy For Children With Autism: A Population-Based Analysis, Teal W. Benevides

Theses and Dissertations

Children with autism spectrum disorder (ASD) represent a growing category of children who have special health care needs. Recent Centers for Disease Control and Prevention (CDC) estimates suggest that 1 in 88 children in the United States have an ASD (CDC, 2012). Due to difficulty with communication, social skills, and restricted and/or repetitive behaviors that comprise current diagnostic criteria (APA, 2013), children with ASD require significant medical, mental health, and therapeutic supports that contribute to greater heath care utilization costs than persons without ASD (e.g., Shimabukuro, Grosse, & Rice, 2008). Therapies such as occupational, physical, and speech therapy are among …

Multimodality Molecular Imaging Of [18f]-Fluorinated Carboplatin Derivative Encapsulated In [111in]-Labeled Liposome, Narottam Lamichhane

Theses and Dissertations

Platinum based chemotherapy is amongst the mainstream DNA-damaging agents used in clinical cancer therapy today. Agents such as cisplatin, carboplatin are clinically prescribed for the treatment of solid tumors either as single agents, in combination, or as part of multi-modality treatment strategy. Despite the potent anti-tumor activity of these drugs, overall effectiveness is still hampered by inadequate delivery and retention of drug in tumor and unwanted normal tissue toxicity, induced by non-selective accumulation of drug in normal cells and tissues. Utilizing molecular imaging and nanoparticle technologies, this thesis aims to contribute to better understanding of how to improve the profile …

The Impact Of Geography, Training, And Experience On Scope Of Practice Among Certified Registered Nurse Anesthetists, Jennifer Greenwood

Theses and Dissertations

The role of Certified Registered Nurse Anesthetists (CRNAs) in the delivery of anesthesia care is evolving given the recent recommendations for Institute of Medicine and provisions in the Affordable Care Act. Despite rigorous clinical training and consistent outcomes studies to support quality care given by CRNAs, the scope of practice of nurse anesthetists is frequently limited, and they do not practice to the full extent of their education and training. As health care spending becomes more constrained and demand for anesthesia services rises, the role of nurse anesthetists as more autonomous providers of anesthesia may be required to maintain access …

A Direct And Indirect Mechanism For Ccr5 In Morphine And Hiv-1 Mediated Neurodegeneration, Elizabeth Podhaizer

Theses and Dissertations

A DIRECT AND INDIRECT MECHANISM FOR CCR5 IN OPIOID AND HIV-1 MEDIATED NEURODEGENERATION By Elizabeth M. Podhaizer, Ph.D. A dissertation submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy at Virginia Commonwealth University. Virginia Commonwealth University, 2014 Major Director: Kurt F. Hauser, Ph.D., Professor of Pharmacology & Toxicology Human immunodeficiency virus (HIV)-1 infection currently affects over 34 million people worldwide, and despite the use of cART, the prevalence of HIV-1 associated neurocognitive impairments (HAND) has not declined. Additionally, other co-morbid factors such as the abuse of injection drugs (i.e. heroin, morphine) increase both the frequency …

Targeting The Endocannabinoid Metabolic Enzymes To Reduce Inflammatory Pain, Sudeshna Ghosh

Theses and Dissertations

Pain is a debilitating condition that presents a problem of clinical relevance. Common analgesics include opioids and non-steroidal anti-inflammatory drugs (NSIADs). Despite different degrees of effectiveness, a major drawback of these analgesic classes is their side effects. For example, side effects associated with opioids include pruritus, respiratory depression, hyperalgesia, constipation, dependence. In addition, chronic use of NSAIDs can cause gastric ulcers. Delta-9 tetrahydrocannabinol (THC), the primary psychoactive constituent of marijuana, produces antinociception in various preclinical models of pain. Similarly, many synthetic cannabinoid receptor agonists produce antinociception in preclinical models of pain. However, their psychomimetic effects dampen interest for their therapeutic …

Combined Antiproliferative Effects Of The Aminoalkylindole Win55,212-2 And Radiation In Breast Cancer Cells, Sean Emery

Theses and Dissertations

The potential antitumor activity of mixed CB1/CB2 cannabinoid receptor agonists, such as the aminoalkylindole WIN55,212-2 (WIN2), has been extensively studied, but little information is available as to their potential interaction with conventional cancer therapies, such as ionizing radiation (IR). In the present work, we investigated the effects of WIN2 on the antiproliferative effects of radiation in human (MCF-7 and MDA-MB-231) and murine (4T1) breast cancer cells, as well as an immortalized human breast epithelial cell line (MCF-10A). WIN2 or radiation alone inhibited breast tumor growth, while the combination of WIN2 and radiation was more effective than either agent alone in …

Dvt Surveillance Program In The Icu: Analysis Of Cost-Effectiveness, Ajai K. Malhotra, Stephanie R. Goldberg, Laura Mclay, Nancy R. Martin, Luke G. Wolfe, Mark M. Levy, Vishal Khiatani, Todd C. Borchers, Therese M. Duane, Michel B. Aboutanos, Rao R. Ivatury

Biostatistics Publications

Background

Venous Thrombo-embolism (VTE – Deep venous thrombosis (DVT) and/or pulmonary embolism (PE) – in traumatized patients causes significant morbidity and mortality. The current study evaluates the effectiveness of DVT surveillance in reducing PE, and performs a cost-effectiveness analysis.

Methods

All traumatized patients admitted to the adult ICU underwent twice weekly DVT surveillance by bilateral lower extremity venous Duplex examination (48-month surveillance period – SP). The rates of DVT and PE were recorded and compared to the rates observed in the 36-month pre-surveillance period (PSP). All patients in both periods received mechanical and pharmacologic prophylaxis unless contraindicated. Total costs – …

Job Attributes, Job Satisfaction And The Return To Health After Breast Cancer Diagnosis And Treatment, Andrew J. Barnes, Nicholas Robert, Cathy J. Bradley

Health Behavior and Policy Publications

Background: As detection and treatment of cancer has advanced, the number of working age women with breast cancer has increased. This study provides new information on the intersection of breast cancer treatment and job tasks and how, together, they impact employed and newly diagnosed women.

Methods: The sample comprised 493 employed women within two months of initiating treatment. Job satisfaction and demands were assessed by pre-diagnosis recall along with measures of mental and physical health and assessed again nine months after initiating treatment. Using seemingly unrelated regression, we tested the effect of job tasks and satisfaction on mental and …

Determinants Of Coverage Decisions In Health Insurance Marketplaces: Consumers' Decision-Making Abilities And The Amount Of Information In Their Choice Environment, Andrew J. Barnes, Yaniv Hanoch, Thomas Rice

Health Behavior and Policy Publications

Objective

To investigate the determinants and quality of coverage decisions among uninsured choosing plans in a hypothetical health insurance marketplace.

Study Setting

Two samples of uninsured individuals: one from an Internet-based sample comprised largely of young, healthy, tech-savvy individuals (n = 276), and the other from low-income, rural Virginians (n = 161).

Study Design

We assessed whether health insurance comprehension, numeracy, choice consistency, and the number of plan choices were associated with participants' ability to choose a cost-minimizing plan, given their expected health care needs (defined as choosing a plan costing no more than $500 in excess of the total …

Childhood Sexual Abuse And The Development Of Recurrent Major Depression In Chinese Women, Jing Chen, Yiyun Cai, Enzhao Cong, Ying Liu, Jingfang Gao, Youhui Li, Ming Tao, Kerang Zhang, Xumei Wang, Chengge Gao, Lijun Yang, Kan Li, Jianguo Shi, Gang Wang, Lanfen Liu, Jinbei Zhang, Bo Du, Guoqing Jiang, Jianhua Shen, Zhen Zhang, Wei Liang, Jing Sun, Jian Hu, Tiebang Liu, Xueyi Wang, Guodong Miao, Huaqing Meng, Yi Li, Guoping Huang, Gongying Li, Baowei Ha, Hong Deng, Qiyi Mei, Hui Zhong, Shugui Gao, Hong Sang, Yutang Zhang, Xiang Fang, Fengyu Yu, Donglin Yang, Tieqiao Liu, Yunchun Chen, Xiaohong Hong, Danhua Gu, Xiaoping Wang, Xiaojuan Liu, Qiwen Zhang, Yihan Li, Yiping Chen, Kenneth S. Kendler, Shenxun Shi, Jonathan Flint

Psychiatry Publications

Background

Our prior study in Han Chinese women has shown that women with a history of childhood sexual abuse (CSA) are at increased risk for developing major depression (MD). Would this relationship be found in our whole data set?

Method

Three levels of CSA (non-genital, genital, and intercourse) were assessed by self-report in two groups of Han Chinese women: 6017 clinically ascertained with recurrent MD and 5983 matched controls. Diagnostic and other risk factor information was assessed at personal interview. Odds ratios (ORs) were calculated by logistic regression.

Results

We confirmed earlier results by replicating prior analyses in 3,950 new …

Genome-Wide And Gene-Based Association Studies Of Anxiety Disorders In European And African American Samples, Takeshi Otowa, Brion S. Maher, Steven H. Aggen, Joseph L. Mcclay, Edwin J. Van Den Oord, John M. Hettema

Psychiatry Publications

Anxiety disorders (ADs) are common mental disorders caused by a combination of genetic and environmental factors. Since ADs are highly comorbid with each other, partially due to shared genetic basis, studying AD phenotypes in a coordinated manner may be a powerful strategy for identifying potential genetic loci for ADs. To detect these loci, we performed genome-wide association studies (GWAS) of ADs. In addition, as a complementary approach to single-locus analysis, we also conducted gene- and pathway-based analyses. GWAS data were derived from the control sample of the Molecular Genetics of Schizophrenia (MGS) project (2,540 European American and 849 African American …

The Omega-3 Fatty Acid Eicosapentaenoic Acid Is Required For Normal Alcohol Response Behaviors In C. Elegans, Richard C. Raabe, Laura D. Mathies, Andrew G. Davies, Jill C. Bettinger

Pharmacology and Toxicology Publications

Alcohol addiction is a widespread societal problem, for which there are few treatments. There are significant genetic and environmental influences on abuse liability, and understanding these factors will be important for the identification of susceptible individuals and the development of effective pharmacotherapies. In humans, the level of response to alcohol is strongly predictive of subsequent alcohol abuse. Level of response is a combination of counteracting responses to alcohol, the level of sensitivity to the drug and the degree to which tolerance develops during the drug exposure, called acute functional tolerance. We use the simple and well-characterized nervous system of Caenorhabditis …

Specific Localization Of Β-Arrestin2 In Myenteric Plexus Of Mouse Gastrointestinal Tract, Hercules T. Maguma, Dipanjana D. De, Sukhada Bhave, William L. Dewey, Hamid I. Akbarali

Pharmacology and Toxicology Publications

Abstract

β-arrestin2 is a key molecule involved in signaling and internalization of activated G protein-coupled receptors including µ-opioid receptors (MOR). Previously we have shown that decreased expression of β-arrestin2 upon chronic morphine is associated with the development of opioid tolerance in the gastrointestinal tract. However, the localization of β-arrestin2 within the gastrointestinal wall is not known. In this study we found that β-arrestin2 is localized in the soma of a select group of neurons in the myenteric ganglia but not in smooth muscle. The density of β-arestin2 was significantly higher in the ileum than the colon. We identified four variants …

Activation Of Nlrp3 Inflammasomes Enhances Macrophage Lipid-Deposition And Migration: Implication Of A Novel Role Of Inflammasome In Atherogenesis, Xiang Li, Yang Zhang, Min Xia, Erich Gulbins, Krishna M. Boini, Pin-Lan Li

Pharmacology and Toxicology Publications

Although Nlrp3 inflammasome activation in macrophages has been shown to be critical for the development of atherosclerosis upon atherogenic stimuli, it remains unknown whether activated Nlrp3 inflammasomes by other non-atherogenic stimuli induce alterations in macrophages that may contribute in the concert with other factors to atherogenesis. Thus, the present study tested the hypothesis that activation of Nlrp3 inflammasomes by ATP, which is a classical non-lipid danger stimulus, enhances the migration of macrophage and increases lipids deposition in macrophages accelerating foam cell formation. We first demonstrated that extracellular ATP (2.5 mM) markedly increased the formation and activation of Nlrp3 inflammasomes in …

Toward A Robust Computational Screening Strategy For Identifying Glycosaminoglycan Sequences That Display High Specificity For Target Proteins, Nehru Viji Sankaranarayanan, Umesh R. Desai

Medicinal Chemistry Publications

Glycosaminoglycans (GAGs) interact with many proteins to regulate processes such as hemostasis, cell adhesion, growth and differentiation and viral infection. Yet, majority of these interactions remain poorly understood at a molecular level. A major reason for this state is the phenomenal structural diversity of GAGs, which has precluded analysis of specificity of their interactions. We had earlier presented a computational protocol for predicting “high-specificity” GAG sequences based on combinatorial virtual library screening (CVLS) technology. In this work, we expand the robustness of this technology through rigorous studies of parameters affecting GAG recognition of proteins, especially antithrombin and thrombin. The CVLS …