Digital Commons Network^™

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 …

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 …

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 …

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 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 …

Mitochondrial Biogenesis And Electrical Properties Of Hpsc-Derived Motor Neurons, Laura O'Brien

Theses and Dissertations

Human pluripotent stem cells (hPSCs), including human embryonic stem cells (hESCs) and induced pluripotent stem cells (iPSCs) hold great promise in the fields of drug development and regenerative medicine. If iPSCs reprogrammed from patient cells replicate what is seen in vivo they may be used as a model of disease. A process that is disrupted in many neurodegenerative diseases is mitochondrial biogenesis. One of these diseases is amyotrophic lateral sclerosis (ALS), which is characterized by loss of motor neurons in the brain and spinal cord. Differentiation of hPSCs into motor neurons offers a way to study a previous unavailable cell …

Development Of Non-Traditional Platinum Anticancer Agents: Trans-Platinum Planar Amine Compounds And Polynuclear Platinum Compounds, Daniel E. Lee

Theses and Dissertations

Development of Non-Traditional Platinum Anticancer Agents: trans-Platinum Planar Amine Compounds and Polynuclear Platinum Compounds

By Daniel E. Lee, 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, 2015

Major Director: Nicholas P Farrell, Ph.D., Professor, Department of Chemistry

Platinum anticancer compounds with cis geometry, similar to cisplatin, have been explored to circumvent the cisplatin resistance; however, they were not considered broadly active in cisplatin cells due to exhibiting similar or same cell death mechanism as cisplatin. Platinum compounds with trans geometry were less studied …

Investigating The Role Of Bptf In Immunoediting In Breast Cancer And Melanoma, Kristen N. Peterson

Theses and Dissertations

In this study, we explore the effects of NURF depletion on the growth of tumors in immune-competent mice. NURF depletion in tumors results in reduced tumor growth in immune-competent mice, suggesting enhanced anti-tumor immunity. Analysis of the tumor microenvironment by flow cytometry revealed a significantly elevated CD8 and progressively elevated activated CD8 phenotype in Bptf KD tumors, possibly contributing to the increase in cell death and decrease in tumor weight observed. Examination of antigen presentation was evaluated using the OT-1 and Pmel-17 models, though no significant difference in cytotoxicity was observed as measured by LDH and/or IFNγ assays. This indicates …

Treatment Decisions Involving Teeth With Intrapulpal Cracks: A Survey Of Endodontists, Sheldon M. Sealey

Theses and Dissertations

There is no universal protocol for diagnosing, treating and managing cracked teeth. The purpose of this survey was to investigate the use of traditional methods of crack detection and to explore how treatment decisions were made using an intrapulpal crack classification. The electronic survey was sent to 1115 active members of the American Association of Endodontists (AAE) and The Digital Office (TDO^™) community. Comparisons were assessed using logistic or repeated-measures regression. The most often used diagnostic method was probing. When the crack involved one wall, 85% of respondents would complete root canal therapy > 50% of the time or …

A Comparison Of Vitamin D Levels In Children With Early Childhood Caries, Vanessa O. Hofilena

Theses and Dissertations

Purpose: To determine if there is an association between early childhood caries (ECC) and vitamin D deficiency, as measured via a serum sample. An exploratory goal was to investigate the possibility of measuring vitamin D with a salivary assay. Methods: Serum samples of patients who were scheduled for a dental or otolaryngology procedure under general anesthesia were assessed for 25-hydroxyvitamin D (25(OH)D), parathyroid hormone and calcium. Results: Our analysis indicates that the vitamin D levels of the controls and ECC group were significantly different. There were significant inverse correlations between: 1) PTH levels and vitamin D and 2) decayed, missing, …

General Dentists' Role In Providing Care To Very Young Children:Pediatric Dentists' Perspective, Shinjni Razdan

Theses and Dissertations

To examine the pediatric dentists’ perspective on level of care to children 0-3 years old by general dentists, an electronic survey was sent out to 5185 AAPD members and 769 responded (response rate: 14.8%). Forty-six percent agreed with a general dentist providing a dental home to children 0-3 years old. Only 24% agreed that general dentists could perform complex restorative and behavior management procedures for 0-3 years old. Younger respondents, pediatric dentists who practice in rural areas or teaching pediatric dentistry, and those who perceived adequate exposure during dental school were more likely to agree on general dentists proving a …

Elucidation Of A Novel Pathway In Staphylococcus Aureus: The Essential Site-Specific Processing Of Ribosomal Protein L27, Erin A. Wall

Theses and Dissertations

Ribosomal protein L27 is a component of the eubacterial large ribosomal subunit that has been shown to play a critical role in substrate stabilization during protein synthesis. This function is mediated by the L27 N-terminus, which protrudes into the peptidyl transferase center where it interacts with both A-site and P-site tRNAs as well as with 23S rRNA. We observed that L27 in S. aureus and other Firmicutes is encoded with a short N-terminal extension that is not present in most Gram-negative organisms, and is absent from mature ribosomes. The extension contains a conserved cleavage motif; nine N-terminal amino acids are …

High School Teacher And Administrator Perceptions Of Student Health Promotion: An Exploratory Study, Sarah B. Conklin

Theses and Dissertations

The current study explored the high school health promotion environment with regards to physical activity, nutrition, and sedentary behaviors from the perspective of high school health and physical education teachers and administrators. Specifically, potential strategies for a prevention program to promote student physical activity participation and healthy eating, and decrease student sedentary time were explored.

Individual semi-structured interviews were conducted with physical education teachers to explore potential strategies to promote student health behaviors. Next, interviews were conducted with high school administrators to determine the feasibility of recommended strategies. Teachers and administrators in the current study expressed a need for strategies …

Relational Coordination: An Exploration Of Nursing Units, An Emergency Department And In-Patient Transfers, Mary Coffey

Theses and Dissertations

Emergency department (ED) crowding is a patient safety concern that has been increasing for more than a decade. Increased visits have resulted in ED crowding, longer wait times, ambulance diversions, and boarding of admitted patients (Hing & Bhuiya, 2012). Numerous factors affect ED crowding. Once various extraneous issues are resolved and a bed is available for a patient, it becomes the responsibility of nurses across unit boundaries to coordinate the patient transfer. This study applies Relational Coordination Theory (RCT) as a framework to provide nurses insight into the relational aspects of their work in the transfer of ED patients to …

Effects Of Hiv-1 Viral Protein Tat On The Viability And Function Of Oligodendroglial Cells, Shiping Zou

Theses and Dissertations

Myelin pallor is frequently reported in HIV patients, and can occur in the CNS prior to other evidence of disease process. Our exploratory studies showed that oligodendrocytes (OLs) are direct targets of HIV-1 Tat (transactivator of transcription). Tat induces a dose-dependent increase of intracellular Ca²⁺ level ([Ca²⁺]_i) in cultured murine OLs, which can be attenuated by ionotropic glutamate receptor (iGluR) antagonists MK801 and CNQX. The Tat-induced [Ca²⁺]_i increase leads to increased death in immature (O4⁺, MBP^-), but not mature (O4⁺, MBP⁺) OLs, over 96 …

Factors That Influence Breast Cancer Diagnoses In Virginia Women 40-64 Years Old Who Utlized The Every Woman’S Life Program 1998-2012, Melanie C. Dempsey

Theses and Dissertations

This dissertation examines sociodemographic determinants and preventive health behaviors among women 40-64 years of age who participated in the Virginia Department of Health’s Every Woman’s Life breast cancer screening program. Utilizing secondary data, this research sought to explore patterns of breast cancer incidence, mammography screening utilization and sources of health information among low-income women.

The Virginia Department of Health provided a large sample size (N=34,942) on which to perform binary logistic regression analyses. Sociodemographic determinants and preventive health behaviors were analyzed as potential influencing factors in the diagnosis of breast cancer, the stage at the time of diagnosis and source …

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 …

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 …

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 …

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 …

Predicting Depression Symptoms Among College Students: The Influence Of Parenting Style, Sarah Whitmire Clark

Theses and Dissertations

This study examined parenting style variables in predicting college students’ depression symptoms. Participants were 989 college students who participated in the first wave of the Spit for Science project (Dick et al., 2011). This study described the prevalence of depression symptoms, including the percentage of the sample endorsing various depression symptoms, and the frequency depression scores were elevated at multiple time points. A hierarchical multiple regression was conducted to examine whether two dimensions of parenting style, Autonomy Granting and Parental Involvement, would interact in predicting depression symptoms in the Junior year. The present study demonstrates that parenting style predicts a …

Restoring Lateral Incisors And Orthodontic Treatment: Perceptions Among General Dentists And Othodontists, Matthew A. Sandretti, Bhavna Shroff, Steven J. Lindauer, Al M. Best

Theses and Dissertations

The purpose of this study was to identify and compare preferences and perceptions of orthodontists and general dentists when restoring peg-shaped lateral incisors. The investigation sought to summarize these preferences with regard to treatment planning, tooth preparation and interdisciplinary communication. A pair of mailed and electronic surveys was distributed to 1,500 general dentists and orthodontists, respectively. The results indicated that general dentists perceived that general dentists held the primary decision-making responsibility, while orthodontists disagreed (P<0.0001). Orthodontists prioritized the treatment goals of Class I canine relationship and overbite/overjet more significantly than general dentists, whom valued tooth proportions more highly (P<0.0001). General dentists reported receiving significantly less input than orthodontists report seeking (P<0.0001).The consensus of both groups showed that the tooth should be positioned centered mesiodistally and guided by the gingival margins incisogingivally. Both groups agree that orthodontists must improve communication to improve treatment results.

An Exploration Of Factors Influencing Attrition From A Pediatric Weight Management Intervention, Melissa Ann Kwitowski

Theses and Dissertations

Childhood obesity is a serious health problem in the United States. Numerous weight management programs attempt to address this issue. However, attrition poses significant treatment efficacy challenges. Understanding attendance and attrition from childhood obesity programs is crucial for effective and appropriate resource utilization. NOURISH+ is a community-based treatment program for parents of overweight and obese children (age 5–11 years, BMI ≥ 85th percentile). The current study investigated attrition from NOURISH+ to enhance understanding of pediatric obesity treatment retention factors. NOURISH+ participants (n=70) completed a questionnaire assessing barriers to adherence and general program feedback. Data were analyzed using frequencies, …

Functional Characterization Of Rai1 In Zebrafish, Joshua S. Beach

Theses and Dissertations

Smith-Magenis Syndrome (SMS; OMIM #182290) is a multiple congenital abnormality and intellectual disability (ID) disorder caused by either an interstitial deletion of the 17p11.2 region containing the retinoic acid induced-1 (RAI1) gene or a mutation of the RAI1 gene. Individuals diagnosed with SMS typically present characteristics such as ID, self-injurious behavior, sleep disturbance, ocular and otolaryngological abnormalities, craniofacial and skeletal abnormalities, neurological and behavioral abnormalities, as well as other systemic defects and manifestations. Previous work by Vyas in 2009 showed temporal expression of rai1 in zebrafish embryos as early as 9 hpf. We hypothesize that there is maternal …

An Association Study Between Adult Blood Pressure And Time To First Cardiovascular Disease, Yongjia Pu

Theses and Dissertations

BACKGROUND: Several studies have demonstrated the association between the time to hypertension event and multiple baseline measurements for adults, yet other survival cardiovascular disease (CVD) outcomes such as high cholesterol and heart attack have been somewhat less considered. The Fels Longitudinal Study (FLS) provides us an opportunity to connect adult blood pressure (BP) at certain ages to the time to first CVD outcomes. The availability of long-term serial BP measurements from FLS also potentially allows us to evaluate if the trend of the measured BP biomarkers over time predicts survival outcomes in adulthood through statistical modeling.

METHODS: When the reference …