Characterization Of A Novel Protease In Staphylococcus Aureus, Adam L. Johnson

Theses and Dissertations

A newly discovered cysteine protease, Prp, has been shown to perform an essential, site-specific cleavage of ribosomal protein L27 in Staphylococcus aureus. In Firmicutes and related bacteria, ribosomal protein L27 is encoded with a conserved N-terminal extension that must be removed to expose residues critical for ribosome function. Uncleavable and pre-cleaved variants were unable to complement an L27 deletion in S. aureus, indicating that this N-terminal processing event is essential and likely plays an important regulatory role. The gene encoding the responsible protease (prp) has been shown to be essential, and is found in all organisms …

Dual Pi3k/Mtor Inhibition With Bez235 Augments The Therapeutic Efficacy Of Doxorubicin In Cancer Without Influencing Cardiac Function, David E. Durrant

Theses and Dissertations

Cancer continues to be a leading cause death in the United States despite improved treatments. Cancerous lesions form after acquiring oncogenic driver mutations or losing tumor suppressor function in normal cells. Traditional therapies have included use of genotoxic substances that take advantage of the increased growth rate and loss of tumor suppressor function to cause cell death. One such drug is the anthracycline antibiotic doxorubicin (DOX). DOX interchelates into DNA and disrupts transcriptional machinery while also poisoning topoisomerase II. This results in single and double stranded DNA breaks, which if severe enough leads to either necrotic or apoptotic cell death. …

Identification Of Candidate Genes For Craniosynostosis, Karen Rymer

Theses and Dissertations

Craniosynostosis is a disorder characterized by the premature fusing of cranial sutures in an infant. Premature closure of these sutures can lead to detrimental consequences on the development of a child. The two broad categories of craniosynostosis are classified as syndromic and nonsyndromic. Nonsyndromic craniosynostosis involves only the fusion of one or more sutures, whereas syndromic craniosynostosis involves other abnormalities throughout the body of the affected individual. Two of the families analyzed in this study were of the syndromic nature, and known FGFR mutations were discovered. However, phenotypical features documented in association with these mutations differed from our individuals. Two …

Synthesis, Surface Functionalization, And Biological Testing Of Iron Oxide Nanoparticles For Development As A Cancer Therapeutic, Stanley E. Gilliland Iii

Theses and Dissertations

Iron oxide nanoparticles are highly researched for their use in biomedical applications such as drug delivery, diagnosis, and therapy. The inherent biodegradable and biocompatible nanoparticle properties make them highly advantageous in nanomedicine. The magnetic properties of iron oxide nanoparticles make them promising candidates for magnetic fluid hyperthermia applications. Designing an efficient iron oxide nanoparticle for hyperthermia requires synthetic, surface functionalization, stability, and biological investigations. This research focused on the following three areas: optimizing synthesis conditions for maximum radiofrequency induced magnetic hyperthermia, designing a simple and modifiable surface functionalization method for specific or broad biological stability, and in vitro and in …

Elaboration And Design Of Α7 Nachr Negative Allosteric Modulators, Osama I. Alwassil

Theses and Dissertations

α7 Neuronal nicotinic acetylcholine receptors are one of two major classes of receptors responsible for cholinergic neurotransmission in the central nervous system. The existence of α7 neuronal nAChRs in different regions of the nervous system suggests their involvement in certain essential physiological functions as well as in disorders such as Alzheimer’s disease (AD), drug dependence, and depression. This project was aimed toward the discovery and development of small–molecule arylguanidines that modulate α7 nAChR function with improved subtype-selectivity through an allosteric approach. Identifying the required structural features of these small molecules allowed optimization of their negative allosteric modulator (NAM) actions at …

Regulation Of Eps8 Dependent Pathways By Src In Head And Neck Squamous Cell Carcinoma, Dhwani Patel

Theses and Dissertations

Head and neck squamous cell carcinoma (HNSCC) is a type of cancer that begins in the epithelial cells that line the mucosal surfaces of the head and neck, including the oral cavity, pharynx, larynx, paranasal sinuses, nasal cavity, and salivary glands. Head and neck cancer is the sixth most common type of cancer with a 5-year survival rate of 60% for all cases. Over the past few years, a subset of cells with stem-like properties, called cancer stem cells, are believed to have tumor-initiation capabilities and are responsible for maintaining on-going tumor growth. Previous data from our lab suggested that …

Effects Of Nicotinic Acetylcholine Receptor Agonists In Assays Of Pain-Stimulated And Pain-Depressed Behavior In Rats, Kelen Freitas

Theses and Dissertations

Though a host of analgesics have been developed to alleviate pain, especially acute pain, significant side effects and a lack of long-term efficacy have encouraged research attempts to pursue novel targets that may be associated with fewer side effects or a more sustained efficacy. Among these new targets are members of the nicotinic family of acetylcholine receptors (nAChRs). The non-selective nAChR agonists nicotine and epibatidine have been shown to function as potent antinociceptive drugs in many acute and chronic preclinical pain models, while nicotine has produced analgesic effects in humans. However, these non-selective nAChRs agonists also produce various side effects, …

A Study Of Errors For 4d Lung Dose Calculation, Nahla K. Sayah

Theses and Dissertations

To estimate the delivered dose to the patient during intra-fraction or throughout the whole treatment, it is important to determine the contribution of dose accumulated at different patient geometries to the overall dose. Dose mapping utilizes deformable image registration to map doses deposited on patient geometries at different times. Inputs to the dose mapping process are the irradiated and reference images, the displacement vector field, and a dose mapping algorithm. Thus accuracy of the mapped dose depends on the DVF and dose mapping algorithm. Dose mapping had been the subject of many research studies however, up to now there is …

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

Theses and Dissertations

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

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

Theses and Dissertations

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

Targeting Autophagy In Multiple Myeloma, Yun Dai

Theses and Dissertations

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

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

Theses and Dissertations

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

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

Theses and Dissertations

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

The Effects Of 7,8-Dihydroxyflavone (7,8-Dhf) On Neuroprotection And Neuroplasticity Follwing A Traumatic Brain Injury, Jennifer M. Romeika

Theses and Dissertations

Aside from preventing traumatic brain injuries (TBIs) altogether, treatment options for TBI typically focus on the secondary biochemical processes that occur in response to the primary mechanical insult. These secondary injuries can lead to apoptosis and necrosis in the days and weeks that follow a TBI. Therefore, finding a treatment that can prevent, reduce, and repair secondary damage is instrumental in the recovery of TBI patients. The flavonoid 7,8-dihydroxyflavone (7,8-DHF) has been identified as a TrkB agonist that mimics the effects of brain derived neurotrophin factor (BDNF). Upon binding to the TrkB receptor, signaling cascades are initiated that can promote …

The Effect Of Statins On Il-33 Mediated Mast Cell Function, Marcela Taruselli

Theses and Dissertations

This study demonstrates original findings of statin effects on IL-33 stimulated mast cells. Statins are a class of drugs used to lower cholesterol production by targeting HMG CoA reductase. These commonly prescribed drugs have been shown to be immunomodulatory. In this study, we have found that pretreatment with statins has a variety of effects on IL-33 stimulated mast cells. Atorvastatin suppresses TNF and IL-6 production, while fluvastatin significantly enhances release of these proinflammatory cytokines in BMMCs. Although they have differing effects on cytokine production, both statins lowered ST2 expression on the cell surface, decreased cell viability, and enhanced expression of …

Lowering The Number Of False Positive Responses To Electric Pulp Tests By Qualifying Patient Response, Katherine Js Lee

Theses and Dissertations

The electric pulp test (EPT) has been shown to be a valuable tool in assessing pulp vitality. One of its drawbacks, however, is its high number of false positives. The purpose of this study was to determine if qualifying the type of sensation elicited by the test could lower the percentage of false positive responses. A retrospective chart review of an eleven-month period was conducted, examining all patients with necrotic teeth tested with the EPT. Of 189 teeth, when the patient responded to EPT at first sensation 23.3% of teeth were incorrectly identified as vital. When the patient was asked …

The Prevalence Of Dietary Supplement Use Among Older Adult Population Using National Health And Nutrition Examination Survey (Nhanes) 2009-2012, Fawaz M. Alotaibi

Theses and Dissertations

Background: Dietary supplements (DS) use has increased in the U.S. in the past 20 years. More than half of the U.S. population reported using DS. There are few studies to our knowledge that have assessed DS use specifically for older adults. In this study we purposed to evaluate the trend of using DS among older adults and to test the association between using DS and several demographics, socioeconomics and health characteristics. The second objective was to evaluate the reasons behind using DS among older adults using a nationally representative database.

Methods: This is a cross sectional study using the most …

Patterns In Chaplain Documentation Of Assessments And Interventions, A Descriptive Study, Kevin E. Adams

Theses and Dissertations

Abstract

PATTERNS IN CHAPLAIN DOCUMENTATION OF ASSESSMENTS AND INTERVENTIONS, A DESCRIPTIVE STUDY

by Kevin Eugene Adams, MDiv

A dissertation submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy at Virginia Commonwealth University

Virginia Commonwealth University, 2015

Diane Dodd-McCue, D.B.A, Department of Patient Counseling

There is increasing emphasis on the importance of evidence-based care provided by all disciplines in healthcare. The Electronic Health Record (EHR) is becoming the standard for communicating assessments, plans of care, interventions, and outcomes of patient care. The spiritual care literature demonstrates the importance of assessing religious/spiritual needs and resources and developing …

Proof-Of-Concept Of Environmental Dna Tools For Atlantic Sturgeon Management, Jameson Hinkle

Theses and Dissertations

Abstract

The Atlantic Sturgeon (Acipenser oxyrinchus oxyrinchus, Mitchell) is an anadromous species that spawns in tidal freshwater rivers from Canada to Florida. Overfishing, river sedimentation and alteration of the river bottom have decreased Atlantic Sturgeon populations, and NOAA lists the species as endangered. Ecologists sometimes find it difficult to locate individuals of a species that is rare, endangered or invasive. The need for methods less invasive that can create more resolution of cryptic species presence is necessary. Environmental DNA (eDNA) is a non-invasive means of detecting rare, endangered, or invasive species by isolating nuclear or mitochondrial DNA (mtDNA) from the …

Low-Flow Domiciliary Oxygen As A Mechanism Of Ongoing Oxidative Stress In Copd Patients, Jill Stulce

Theses and Dissertations

Healthcare costs are escalating in the U.S., with a projected 48 trillion dollars by 2021. More than ever medical researches are obligated to ensure that costly treatment modalities are safe and effective. Chronic obstructive pulmonary disease (COPD) is a costly and debilitating disease, ranked as the third leading cause of death in America. Currently, treatment for COPD consists of anti-inflammatory agents, bronchodilators, antibiotics and supplemental oxygen when hypoxemia or clinical manifestations ensue. Oxidative stress is central to the pathology of COPD. Supplemental oxygen has been substantiated as an instigator of oxidative stress; however, LFDO has not been evaluated as a …

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

Theses and Dissertations

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

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

Theses and Dissertations

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

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

Economic Impact Of Waste In Prescribing, Dispensing, And Medication Consumption In The United States, Sarah Almanie

Theses and Dissertations

Abstract

ECONOMIC IMPACT OF WASTE IN PRESCRIBING, DISPENSING, AND MEDICATION CONSUMPTION IN THE UNITED STATES

By Sarah A. Almanie, M.S.

A thesis submitted in partial fulfillment of the requirements for the degree of Master of Science at Virginia Commonwealth University.

Virginia Commonwealth University, 2015.

Major Director: David A. Holdford, R.Ph., M.S., Ph.D., FAPhA

Professor

Department of Pharmacotherapy and Outcomes Science

OBJECTIVES: This research examines waste associated with the medication use process which consists of unfilled prescriptions, abandoned prescriptions, or unused prescription medications. The aim of this study is to quantify the direct medical costs of medication waste in delivery of …

Restorative Characteristics Of Intrapulpally Cracked Teeth, Charles M. Beavers

Theses and Dissertations

Cracked teeth have long presented a diagnostic challenge. Previous investigators have considered possible predictive factors, many of which revolve around the tooth’s restorative characteristics. Few have investigated the restorative status of teeth with cracks extending into the pulp chamber. The purpose of this investigation was to determine the prevalence of the different types of restorations present in intrapulpally cracked teeth and determine any other restorative factors that may aid in predicting the presence or extent of an intrapulpal crack. Intrapulpally cracked molars requiring endodontic therapy at the VCU Graduate Endodontic Practice were included in this study. For each tooth, the …

The Effectiveness Of A Preventive Recall Strategy In Children Following Dental Rehabilitation Under General Anesthesia, Katherine A. Nordeen

Theses and Dissertations

Purpose: This was a pilot study to assess the impact of a preventive strategy following full-mouth dental rehabilitation (FMDR) under general anesthesia in children with early childhood dental caries.

Methods: Sixty-six patients completed FMDR and were included in the analysis. At the consultation visit, caries risk assessment (CRA) and dental exam information were recorded, and caregivers completed an oral health knowledge (OHK) questionnaire. Patients returned for a post-surgery and recall visit. Caregivers received oral hygiene instructions in a motivational-interviewing style.

Results:At the consultation visit all patients were high risk. At the post-surgery visit, only 47% remained high risk …

Understanding The Function Of Dyrk1a Through Characterization Of Its Interacting Proteins, Varsha Ananthapadmanabhan

Theses and Dissertations

DYRK1A is a protein kinase encoded by a gene implicated in Down syndrome pathogenesis. Loss of DYRK1A could promote oncogenic transformation. However, the regulation and substrates of DYRK1A are not fully understood. MudPIT proteomic analysis revealed novel DYRK1A interacting proteins with poorly characterized or even unknown functions. Therefore, the aim of this thesis was to understand the function of DYRK1A through the characterization of its interacting proteins. To achieve this aim, we established stable cell lines expressing these proteins and confirmed the interactions between DYRK1A and seven candidate binding partners. Furthermore, we found that all novel DYRK1A-interacting proteins also bind …

Esthetic Preferences Of Maxillary Incisor Labiolingual Inclination Across Races, Elvi M. Barcoma

Theses and Dissertations

Abstract

ESTHETIC PREFERENCES FOR MAXILLARY INCISOR LABIOLINGUAL INCLINATION ACROSS RACES

by Elvi Marie Barcoma, D.D.S.

A thesis submitted in partial fulfillment of the requirements for the degree of Master of Science in Dentistry at Virginia Commonwealth University

Virginia Commonwealth University, 2015

Major Director: Bhavna Shroff, D.M.D., M.Dent.Sc, Program Director, Orthodontics

Objective: To determine if people of different racial backgrounds prefer different amounts of

maxillary incisor labiolingual inclination from a smiling profile view.

Materials and Methods: An electronic survey was created with smiling profile images of an African-American female and a White female with varying degrees of maxillary incisor labiolingual inclination. …

Incorporation Of Molecular Diagnostics Into Medical Laboratory Science Curriculum: Clinical Facilities Expectations. An Asynchronous, Iterative, Online Delphi Study., Barbara Kraj

Theses and Dissertations

The medical laboratory science (MLS) profession is in need for published molecular diagnostics competency-based standards and curriculum. To assess their expectations of new MLS graduates, professionals performing and supervising performance of clinical molecular assays were surveyed to rate the importance of relevant cognitive and psychomotor learning objectives. A modified, asynchronous, iterative online Delphi process was utilized for assessment of consensus on the importance of the objectives. The survey was delivered through online REDCap application. Program directors of 221 MLS programs accredited by the National Accrediting Agency for Clinical Laboratory Science (NAACLS) were asked to forward the first Delphi survey to …

Conduction States Of The Human Dopamine Transporter, Krasnodara Cameron

Theses and Dissertations

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

In-Vitro Assessment Of A Novel Bracket's Effect On Resistance To Sliding, James Blackburn

Theses and Dissertations

Friction, binding and notching are the factors that contribute to resistance to sliding during orthodontic tooth movement. However, most attempts at reducing resistance aim only to reduce the archwire/ligature friction. In this study, a novel bracket with a unique design aimed to reduce all three components of resistance to sliding. Four types of brackets (passive and active self-ligating, traditionally ligated and the novel bracket, (n=5, each) were tested at 0, 2, 4, 6, and 8ᵒ of tip on a 0.019 x 0.025”archwire. The resistance to sliding values were recorded. At 0ᵒ, the passive self-ligating and novel bracket showed reduced resistance …