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2012

Virginia Commonwealth University

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Full-Text Articles in Medicine and Health Sciences

Regulation Of The Mouse And Human Β-Globin Genes By Krüppel Like Transcription Factors Klf1 And Klf2, Yousef N. Alhashem Dec 2012

Regulation Of The Mouse And Human Β-Globin Genes By Krüppel Like Transcription Factors Klf1 And Klf2, Yousef N. Alhashem

Theses and Dissertations

Krüppel-like factors KLF1 and KLF2 are closely related transcription factors with three zinc finger domains in their carboxy-termini. KLF1 (erythroid Krüppel-like factor, or EKLF) plays essential roles in embryonic and adult erythropoiesis. KLF2 is a positive regulator of the mouse and human embryonic β- globin genes. KLF1 and KLF2 have overlapping roles in embryonic erythropoiesis, as demonstrated using single and double knockout (KO) mouse models. Ablation of the KLF1 or KLF2 gene causes embryonic lethality, and double KO embryos are more anemic and die sooner than either single KO. We have shown that KLF1 and KLF2 positively regulate the human …

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From Linkage To Gwas: A Multifaceted Exploration Of The Genetic Risk For Alcohol Dependence, Amy Adkins Dec 2012

From Linkage To Gwas: A Multifaceted Exploration Of The Genetic Risk For Alcohol Dependence, Amy Adkins

Theses and Dissertations

Family, twin and adoption studies consistently suggest that genetic factors strongly influence the risk for alcohol dependence (AD). Although the literature supports the role of genetics in AD, identification of specific genes contributing to the etiology of AD has proven difficult. These difficulties are due in part to the complex set of risk factors contributing to the development of AD. These risk factors include comorbidities with other clinical diagnoses and behavioral phenotypes (e.g., major depression), physiological differences that contribute to the differences between people in their level of response to ethanol (e.g., initial sensitivity) and finally the large number of …

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Medication-Related Problems Experienced By Patients During Transitions To Assisted Living, Deanna Flora Dec 2012

Medication-Related Problems Experienced By Patients During Transitions To Assisted Living, Deanna Flora

Theses and Dissertations

Medication reconciliation is a systematic and comprehensive review of medication regimens during care transitions aiming to prevent adverse drug events. Poorly executed transitions negatively impact patient welfare and cause financial burden. Medication-related problems (MRPs) experienced during transitions to an assisted living facility (ALF) were evaluated. Data was collected from pharmacy records for transitions to an ALF over three months, including demographics, medications, potentially inappropriate medications, and MRPs. MRPs were categorized and summarized using descriptive statistics. Forty-five patients (71% female) experienced 59 transitions. Average age was 85.6 years. Median length of stay away from the ALF was three days. There were …

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The Economic Burden Of Opioid Poisoning In The United States And Determinants Of Increased Costs In Opioid Poisoning, Timothy Inocencio Dec 2012

The Economic Burden Of Opioid Poisoning In The United States And Determinants Of Increased Costs In Opioid Poisoning, Timothy Inocencio

Theses and Dissertations

Introduction: Opioid poisoning has been rapidly increasing in the past decade, and has been driven in large part due to increases in opioid prescribing. This has been accompanied by intervention efforts aimed at preventing and reversing opioid poisoning through naloxone prescription programs. Current literature have not quantified the economic burden of opioid poisoning. Understanding this information can help inform these efforts and bring light to this growing problem. In addition understanding various determinants of increased costs can help to identify the types of populations more likely to have greater costs. Main Objectives: The objectives are 1) to quantify the economic …

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Text Messaging As Adjunct To Community Based Weight Management Program, Claudia Bouhaidar Dec 2012

Text Messaging As Adjunct To Community Based Weight Management Program, Claudia Bouhaidar

Theses and Dissertations

Obesity ascending rates are still a public health priority. The primary aim of the study was to evaluate the effect of tailored text messages on body weight change in overweight and obese adults in a community based weight management program. A secondary aim was to detect behavioral changes in the same population. The study design was quasi-experimental with pre and posttest analysis, conducted over 12 weeks. A total of 28 participants were included in the analysis. Body weight, eating behaviors, exercise and nutrition self-efficacy, attitude toward mobile technology, social support and physical activity were assessed at baseline and at 12 …

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Characterization Of The Expression Of The Intercellular Adhesin Locus In Staphylococcus Aureus, Jamie Brooks Dec 2012

Characterization Of The Expression Of The Intercellular Adhesin Locus In Staphylococcus Aureus, Jamie Brooks

Theses and Dissertations

Poly-N-acetylglucosamine (PNAG) is an important Staphylococcus aureus virulence factor. It is a major component of the extracellular polymeric matrix in biofilms, and contributes to resistance to the innate immune response. The proteins encoded in the icaADBC (intercellular adhesin) operon are responsible for PNAG production. Here, we present evidence of a new mechanism of phase variation for switching off PNAG production that involves slipped strand mutagenesis, along with further insight into the regulation and expression of the icaADBC operon. S. aureus strain MN8m (mucoid) is a spontaneous mutant of strain MN8 (non-mucoid). It is characterized by constitutive overproduction of PNAG, resulting …

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The Role Of Megalin In The Transport Of Aminoglycosides Across Human Placenta, Amal Akour Dec 2012

The Role Of Megalin In The Transport Of Aminoglycosides Across Human Placenta, Amal Akour

Theses and Dissertations

Background: Intra-amniotic infections (IAIs) are common complications of labor and delivery. If inadequately treated, these infections can lead to significant morbidity and mortality in the mother and the fetus. Intrapartum aminoglycoside (AG) administration is recommended for the management of IAIs. AGs are known to cross the placenta and achieve bactericidal concentrations in fetal serum. However, the highest and most persistent fetal levels are achieved in renal tissue. So, the fetus may be vulnerable to the nephrotoxic effects of AGs. Megalin, a 600 kDaendocytic receptor, is responsible for the uptake of AGs into renal proximal tubular epithelial cells. This receptor is …

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Diffuse Traumatic Axonal Injury Within The Visual System: Implications For Visual Pathway Reorganization, Jiaqiong Wang Dec 2012

Diffuse Traumatic Axonal Injury Within The Visual System: Implications For Visual Pathway Reorganization, Jiaqiong Wang

Theses and Dissertations

Traumatic brain injury is a major health problem with much of its morbidity associated with traumatic axonal injury (TAI). To date, significant insight has been gained into the initiating pathogenesis of TAI. However, the specific anterograde and retrograde sequelae of TAI are poorly understood because the diffuse nature of TAI complicates data analysis. To overcome this limitation, we subjected transgenic mice expressing yellow fluorescent protein (YFP) within the visual system to central fluid percussion injury, and consistently generated diffuse TAI within the optic nerve that could easily be followed in the organized YFP positive fibers. We demonstrated progressive axonal swelling, …

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Perceived Stress And Surgical Wound Cytokine Patterns, Valentina Lucas Nov 2012

Perceived Stress And Surgical Wound Cytokine Patterns, Valentina Lucas

Theses and Dissertations

Normal wound healing is a complex process that occurs in overlapping phases and depends upon interactions of the patient, environment and a large number of cells, growth factors, cytokines, chemokines, and other biochemical mediators. Psychological stress has been shown to adversely affect the normal wound healing process through its impact on cellular immunity. Cellular immunity impacts wound healing through the production and regulation of many of the above biochemical mediators of wound healing. The purpose of this pilot study was to examine the relationships among pre- and post-operative psychological stress experienced by women who were undergoing either immediate or delayed …

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Ige Enhances B Cell-Derived Exosomal Induced T Cell Proliferation, Brooks Keith Nov 2012

Ige Enhances B Cell-Derived Exosomal Induced T Cell Proliferation, Brooks Keith

Theses and Dissertations

For many years it has been known that the injection of antigen bound to an antibody leads to more than a 1000-fold increase in antigen specific antibody response. This observation holds true for IgE, which is dependent upon CD23 expression, as this enhancement is not present in mice deficient in CD23. It also has been shown that when mice are injected with IgE-antigen complexes also display an increase in antigen specific T cell proliferation. While there are published studies that demonstrate a role for B cell derived exosomes in the activation and proliferation of T cells, none have focused upon …

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Role Of Tyrosyl-Dna Phosphodiesterase (Tdp 1) On Repair Of 3′-Phosphoglycolate (3′- Pg) Terminated Dna Double-Strand Breaks (Dsbs) And In Response To Oxidative Stress, Tong Zhou Nov 2012

Role Of Tyrosyl-Dna Phosphodiesterase (Tdp 1) On Repair Of 3′-Phosphoglycolate (3′- Pg) Terminated Dna Double-Strand Breaks (Dsbs) And In Response To Oxidative Stress, Tong Zhou

Theses and Dissertations

DNA DSBs are most toxic to cells because they can lead to genomic rearrangements and even cell death. Most DSBs induced by ionizing radiation or radiomimetic drugs such as calicheamicin and bleomycin, bear 3′-phosphate or 3′- PG moieties that must be removed to allow subsequent gap filling and ligation. DSBs can be repaired by two main pathways: the homologous recombination (HR) pathway and the non-homologous end-joining (NHEJ) pathway, NHEJ is the primary repair pathway in mammalian cells. While HR repairs single strand breaks (SSBs) or DSBs accurately by using an undamaged copy of the sequence mostly at late S phase …

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"Being Certain": Moral Distress In Critical Care Nurses, Marian Baxter Nov 2012

"Being Certain": Moral Distress In Critical Care Nurses, Marian Baxter

Theses and Dissertations

Published literature has focused on understanding moral distress from a descriptive standpoint. Missing from the literature is an exploration of the role a nurse can play in his/her/own moral distress.A qualitative study with an interpretive design incorporated Clandinin and Connelly' narrative methodology. Results highlighted assumptions were made by participants in the absence of resources, which led them to" know the right action to take" from their own perspective.

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Investigating A Model For Fetal Alcohol Damage In Caenorhabditis Elegans, Lindsay Kondo Nov 2012

Investigating A Model For Fetal Alcohol Damage In Caenorhabditis Elegans, Lindsay Kondo

Theses and Dissertations

Alcohol use and abuse has many harmful effects, especially to children exposed prenatally, including fetal alcohol spectrum disorders (FASDs). The disabilities due to fetal alcohol exposure continue throughout life and cause major financial burdens to society. The molecular mechanisms underlying FASDs are not well understood. We have taken a genetic approach to characterize ethanol’s effect on changing a discrete cell fate decision during embryogenesis in the nematode, Caenorhabditis elegans (C. elegans). Our preliminary data suggest that ethanol can affect the development of AWC neurons, a pair of olfactory neurons in C. elegans. We suggest that lipids can protect AWC neurons …

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Costs And Use Of Oral Anti-Cancer Medications Among Senior Medicare Part D Beneficiaries, Nantana Kaisaeng Nov 2012

Costs And Use Of Oral Anti-Cancer Medications Among Senior Medicare Part D Beneficiaries, Nantana Kaisaeng

Theses and Dissertations

Oral cancer drugs are branded and expensive medications that generally do not have generics available. The restrictions of the Medicare Part D program, including the coverage gap and high cost-sharing, and the high cost of oral chemotherapy may lead to patients’ non-adherence to medication. Few studies have examined the cost and utilization of oral anti-cancer medications. This study will be the first to examine the costs associated with the use of oral anti-cancer medications and the impact of cost-sharing and type of prescription drug subsidy on medication discontinuation in the Medicare Part D elderly population. Objectives: To determine the usage …

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Epid-Based Dose Verification For Adaptive Radiotherapy, Joseph Gardner Nov 2012

Epid-Based Dose Verification For Adaptive Radiotherapy, Joseph Gardner

Theses and Dissertations

Dose verification is a critical component of adaptive radiotherapy, as it provides a measurement of treatment delivery success. Based on the measured outcome, the plan may be adapted to account for differences between the planned dose and the delivered dose. Although placement of an EPID behind the patient during treatment allows for exit dosimetry which may be used to reconstruct the delivered patient dose via backprojection of the fluence, there have not been any studies examining the basic assumption of backprojection-based dose verification: that deviations between the expected and delivered exit fluences are totally caused by errors in the delivered …

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Heart Failure Symptom Clusters And Functional Status, Janet Herr Nov 2012

Heart Failure Symptom Clusters And Functional Status, Janet Herr

Theses and Dissertations

Abstract HEART FAILURE SYMPTOM CLUSTERS AND FUNCTIONAL STATUS Janet Kay Herr 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 2012 Major Director: Dr. Jeanne Salyer, Ph.D., R.N., F.N.A.P Associate Professor, Adult Health & Nursing Systems Clinical assessment of heart failure includes symptom identification and the evaluation of the relationship of symptoms to functional status. Symptom clusters are groups of at least 2 or 3 co-occurring symptoms that are related but are independent of other groups of symptoms. The objectives of this study are to: …

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A New Approach To Dried Blood Spot Analysis For Newborn Screening Using High Resolution Liquid Chromatography Tandem Mass Spectrometry, John H. Miller Iv Nov 2012

A New Approach To Dried Blood Spot Analysis For Newborn Screening Using High Resolution Liquid Chromatography Tandem Mass Spectrometry, John H. Miller Iv

Theses and Dissertations

The primary purpose of newborn screening is to quickly identify children that are at risk of having a specific disorder in order to start treatment, prevent early death and reduce the chances of permanent physical or mental damage. The current and widely accepted approach used for identification of metabolism disorders involves a flow injection analysis with mass spectrometry detection of acylcarnitines and amino acids. Although this approach is widely accepted and has shown to be sufficient for identification of multiple metabolism disorders the method is not fully quantitative and results often have to be confirmed by second-tier tests. The primary …

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The Role Of P62 In Osteoclastogenesis And Paget’S Disease Of Bone, Tamer Hadi Nov 2012

The Role Of P62 In Osteoclastogenesis And Paget’S Disease Of Bone, Tamer Hadi

Theses and Dissertations

Paget’s disease (PDB) is the second most common metabolic bone disease after osteoporosis, affecting up to 3% of adults over age 55. It is characterized by focal lesions of bone resorbed by hyperactive osteoclasts coupled with rapid formation of highly disorganized, low quality bone formed by osteoblasts. Such lesions cause skeletal deformity, fractures, and other symptoms that significantly decrease quality of life. In 2001, mutations in the SQSTM1/p62 gene were found in a subset of Paget’s patients. The work summarized in this dissertation sought to answer two broad questions: what is the function of p62 in normal bone homeostasis and …

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The Role Of Magl Inhibition In Nicotine Withdrawal And Reward, Pretal Muldoon Nov 2012

The Role Of Magl Inhibition In Nicotine Withdrawal And Reward, Pretal Muldoon

Theses and Dissertations

ROLE OF MAGL INHIBITION IN NICOTINE WITHDRAWAL AND REWARD. A dissertation submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy at Virginia Commonwealth University. by Pretal Ishvarlal Patel Muldoon Director: M. Imad Damaj, PhD Professor, Department of Pharmacology and Toxicology Tobacco use is one of the leading causes of preventable deaths worldwide. Nicotine, the main psychoactive component of tobacco, sustains and initiates tobacco addiction. Cessation of nicotine induces a dependence withdrawal syndrome. Recent in vivo studies indicate that the endocannabinoid (EC) system modulates both nicotine reward and withdrawal. The purpose of this proposal is to …

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The Effect Of Physician Ownership On Quality Of Care For Outpatient Procedures, Xinliang Liu Nov 2012

The Effect Of Physician Ownership On Quality Of Care For Outpatient Procedures, Xinliang Liu

Theses and Dissertations

Ambulatory surgery centers (ASCs) play an important role in providing surgical and diagnostic services in an outpatient setting. They can be owned by physicians who staff them. Previous studies focused on patient “cherry picking” and over-utilization of services due to physician ownership. Few studies examined the relationship between physician ownership and quality of care. Using a retrospective cohort of patients who underwent colonoscopy, this study examined the effect of physician ownership of ASCs on the occurrence of adverse events after outpatient colonoscopy. Agency theory is used to as a conceptual framework. Depending on the extent to which consumers are able …

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Capture And Characterization Of Dioxygen Reactive Intermediates In Cyp51 Catalysis, Gareth Kent Jennings Oct 2012

Capture And Characterization Of Dioxygen Reactive Intermediates In Cyp51 Catalysis, Gareth Kent Jennings

Theses and Dissertations

The cytochromes P450 (CYPs) are a superfamily of biological catalysts that are ubiquitous throughout the biological domain. CYPs are heme-b containing monooxygenases which oxidize substrates with the help of accessory redox partners. CYP substrates include endogenous compounds required for many biological functions and homeostasis, such as steroids, as well as the majority of clinically used drugs and environmental xenobiotics. The majority of studies that have been performed to date are on P450cam (CYP101) from Pseudomonas putida. Of the numerous reactions catalyzed by CYPs, unactivated carbon-carbon bond cleavage, is one of particular versatility. Being unique in their catalytic mechanisms, the C-C …

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On The Genetic And Environmental Associations Between Body Composition, Depression Symptoms And Smoking Behavior., Roseann Peterson Oct 2012

On The Genetic And Environmental Associations Between Body Composition, Depression Symptoms And Smoking Behavior., Roseann Peterson

Theses and Dissertations

Obesity is a serious public health crisis and recent estimates of its incidence are the highest in United States history, with 35% and 17% of American adults and children affected, respectively. The clinical definition of adult obesity is operationalized as a body mass index (BMI) greater than 30 kg/m2. Although the prevalence of common obesity has increased dramatically over the past 30 years–largely thought to be due to changes in the environment, such as high calorie diets and sedentary lifestyles—twin and family studies have shown consistently that relative body weight is under considerable genetic influence in both children and adults, …

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Examining Alcohol Dependence And Its Correlates From A Genetically Informative Perspective, Laura Hack Sep 2012

Examining Alcohol Dependence And Its Correlates From A Genetically Informative Perspective, Laura Hack

Theses and Dissertations

Alcohol dependence (AD) is a serious and common public health problem that contributes to great societal, medical, and legal costs. It has taken work from multiple disciplines, including developmental psychology, genetic epidemiology, and molecular genetics, to achieve our current understanding of environmental and genetic risk factors for AD as well as its variable developmental trajectories. Nevertheless, there is still much to be learned in order to improve treatment outcomes. One approach to augmenting our understanding of this disorder is through genetically informative study designs that either examine risk in aggregate or assess specific susceptibility variants. In this dissertation, we utilize …

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Using Genetic Information In Risk Prediction For Alcohol Dependence, Jia Yan Sep 2012

Using Genetic Information In Risk Prediction For Alcohol Dependence, Jia Yan

Theses and Dissertations

Family-based and genome-wide association studies (GWAS) of alcohol dependence (AD) have reported numerous associated variants. The clinical validity of these variants for predicting AD compared to family history has not yet been reported. These studies aim to explore the aggregate impact of multiple genetic variants with small effect sizes on risk prediction in order to provide a clinical interpretation of genetic contributions to AD. Data simulations showed that given AD’s prevalence and heritability, a risk prediction model incorporating all genetic contributions would have an area under the receiver operating characteristic curve (AUC) approaching 0.80, which is often a target AUC …

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Role Of Autophagy In The Response Of Hs578t Breast Tumor Cells To Radiation, Shweta Chakradeo Sep 2012

Role Of Autophagy In The Response Of Hs578t Breast Tumor Cells To Radiation, Shweta Chakradeo

Theses and Dissertations

Breast cancer is the most commonly observed cancer type in women and is the second leading cause of cancer death in women. Radiation can be used to debulk tumors prior to surgery as well as to treat patients after surgery and/or chemotherapy. Previous studies from our laboratory have shown that the anti –malarial drug chloroquine sensitizes breast cancer cell lines to radiation by suppression of autophagy which is a conservative catabolic process that can be cytoprotective. The scientific literature has demonstrated that many tumor cell systems undergo cytoprotective autophagy and that pharmacological or genetic inhibition of autophagy leads to other …

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Cellular Effects Of Platinum Chemotherapeutics: Alterations By Antidepressants And Heparan Sulfate Proteoglycans, Brigitte Engelmann Sep 2012

Cellular Effects Of Platinum Chemotherapeutics: Alterations By Antidepressants And Heparan Sulfate Proteoglycans, Brigitte Engelmann

Theses and Dissertations

The work discussed here is divided into two projects. The first project involves the interactions between antidepressants and the platinum based chemotherapeutics while the second project begins to investigate possible implications of a recently discovered uptake mechanism for positively charged platinum drugs. Gaining understanding of the interactions between antidepressants and platinum-based chemotherapeutics is important due to the frequency with which they are prescribed together. Although using a combination regimen of antineoplastics is beneficial to the patient, not all drug interactions are. For instance, many of the serotonin reuptake inhibitors have been shown to decrease the efficacy of tamoxifen. Desipramine, a …

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Role Of Nicotinic Acetylcholine Receptors In Experimental Colitis, Shakir Alsharari Aug 2012

Role Of Nicotinic Acetylcholine Receptors In Experimental Colitis, Shakir Alsharari

Theses and Dissertations

Substantial evidence in the literature shows that tobacco smoking has complex and divergent effects on inflammatory bowel diseases (IBD). It ameliorates ulcerative colitis (UC); whereas it aggravates the risk of Crohn’s disease (CD) and affects the disease course and severity. Studies have shown that nicotine has a positive influence on symptoms of UC. Also, it is demonstrated that nicotinic acetylcholine receptor, especially α7 subunit plays an essential component in the vagus nerve-based cholinergic anti-inflammatory effects. In the present study, we explored the effect of nicotine and α7 nicotinic agonists treatment in the DSS colitis mouse model. We also investigated the …

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Influence Of Electrostatic Charge Upon The Deposition Behavior Of Pharmaceutical Aerosols Within Cascade Impactors, Megha Mohan Aug 2012

Influence Of Electrostatic Charge Upon The Deposition Behavior Of Pharmaceutical Aerosols Within Cascade Impactors, Megha Mohan

Theses and Dissertations

Cascade impactors, routinely used for in vitro particle size characterization of pharmaceutical aerosols, are calibrated using dilute, charge-neutralized, monodisperse aerosols. But pharmaceutical aerosols are known to generate concentrated, inherently charged, polydisperse aerosol clouds. A computational model of the Andersen Cascade Impactor (ACI) suggested that the presence of charge on aerosol particles may influence their deposition within the ACI, but experimental validation of the model is warranted. This dissertation investigates the influence of electrostatic charge upon the deposition behavior of aerosols within cascade impactors, to address the impact of charge on particle size characterization. The influence of applied charge upon the …

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Investigating Synergy Between Ribonucleotide Reductase Inhibitors And Cmv Antivirals, Sukhada Bhave Aug 2012

Investigating Synergy Between Ribonucleotide Reductase Inhibitors And Cmv Antivirals, Sukhada Bhave

Theses and Dissertations

Cytomegalovirus (CMV) infections remain a significant problem in congenitally infected infants and immunocompromised individuals. Modest antiviral activities of currently approved drugs coupled with dose-limiting toxicities restrict effectiveness and promote development of resistance. The potential for ribonucleotide reductase (RR) inhibitors hydroxyurea (HU), Didox, and Trimidox to synergize, through reduction of nucleotide pools, with the deoxynucleotide analog Ganciclovir (GCV) was examined. A yield reduction assay that utilizes luciferase expressed by a recombinant virus as a surrogate measure of viral infectious units was developed and used to determine effective dose ranges for each drug. RR inhibitors exhibited intrinsic anti-CMV activities on their own …

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Discovery And Biophysical Characterization Of Allosteric Inhibitors Of Factor Xia (Fxia), Malaika Argade Aug 2012

Discovery And Biophysical Characterization Of Allosteric Inhibitors Of Factor Xia (Fxia), Malaika Argade

Theses and Dissertations

Thrombosis is one of the leading causes of mortality and morbidity that is associated with myocardial infarction, stroke and pulmonary embolism. Anti-thrombotic agents which intend to reduce the occurrence and severity of thrombosis usually target the enzymes of the coagulation cascade. FXIa, a 160 kDa homodimer is gaining popularity of late as a potential target for anti-thrombotic agents due to its relative safety. A number of inhibitors which target the active site of FXIa have been reported but to our knowledge there have been no inhibitors which act via an allosteric mechanism. The aim of this project was to screen …

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