Generation And Delivery Of Charged Aerosols To Infant Airways, Landon T. Holbrook

Theses and Dissertations

The administration of pharmaceutical aerosols to infants on mechanical ventilation needs to be improved by increasing the efficiency of delivery devices and creating better ways of evaluating potential therapies. Aerosolized medicines such as surfactants have been administered to ventilated infants with mixed results, but studies have shown improvement in respiratory function with a much lower dose than with liquid instillation through an endotracheal tube (ETT). An aerosolized medicine must be transported through the ventilation tubing and deposit in the lungs to have the desired therapeutic response.

This work has taken a systematic approach to (i) develop new devices for the …

Characterizarion Of The Regulation And Function Of Neisseria Gonorrhoeae Tonb-Dependent Transporters: Tdfg, Tdfh And Tdfj, Sophonie Jean

Theses and Dissertations

The obligate human pathogen Neisseria gonorrhoeae successfully overcomes host strategies to limit essential nutrients, termed “nutritional immunity” by expression of TonB-dependent transporters (TdTs): outer membrane receptors that facilitate nutrient transport in an energy-dependent manner. N. gonorrhoeae encodes eight TdTs, five of which facilitate utilization of iron or iron-chelates from host derived proteins including transferrin, lactoferrin and hemoglobin, in addition to siderophores from neighboring bacteria. The transferrin utilization system was previously shown to be critical for establishing infection in human males; demonstrating the possible contributions of TdTs to gonococcal pathogenesis. As such, studies describing the biological function and contribution to pathogenesis …

The Slc22 Transporter Family: Novel Insights To Roles In Drug Efficacy, Drug-Drug Interactions And Mood Disorders, Xiaolei Pan

Theses and Dissertations

Numerous studies have demonstrated the impact of organic cation (OCTs; SLC22 family) and anion transporters (OATs; SLC22 family) on the efficacy and safety of clinically important therapeutics. To be specific, OCTs and OATs have been identified as determinants for uptake into and secretion from enterocytes, hepatocytes and renal proximal tubular cells, and are frequent sites of drug-drug interaction (DDI). In addition, OCTs expressed in brain are components of the low-affinity, high capacity clearance pathway (uptake-2) for biogenic monoamine neurotransmitters. As a result, OCTs may represent novel targets for mood disorders.

The inhibitory effects of several therapeutic agents, designed drugs and …

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 …

The Effect Of Optogenetic Manipulation Of Ss Interneurons Within Malformed, Epileptogenic Cortex, Nicole Ekanem

Theses and Dissertations

A large percentage of individuals with intractable epilepsies have an accompanying cortical malformation, the underlying cellular mechanisms of which are poorly understood. It is known however that in an animal model for one such malformation, polymicrogyria, epileptogenesis occurs most easily from an adjacent area termed the paramicrogyral region (PMR). Previous studies implicate SS interneurons as a potential contributor to this pathology, which lead to our hypothesis: in PMR, SS interneurons exert a higher modulatory influence on excitatory pyramidal cells, as compared to the same by SS interneurons within homologous control cortex.

Using a freeze-lesion model for polymicrogyria in transgenic mice …

The Characterization Of A Putative Virulence Factor Expressed By Sneathia Amnii, Amy Sanford

Theses and Dissertations

Preterm birth, defined at birth before 37 weeks gestation, affects millions of newborns worldwide every year. Preterm birth is a leading cause of infant morbidity and mortality. One major cause of preterm birth is preterm premature rupture of membranes (PPROM), which can be triggered by bacterial infection and inflammation. A bacterial species that has been implicated in preterm birth and other obstetric complications is Sneathia amnii. The goals of this study were to observe cytopathogenic effects caused by S. amnii strain Sn35 and identify putative virulence factors causing those effects. Sn35 was able to adhere to, invade, and damage/kill …

Reproductive Health And Behavior: The Role Of Abuse And Couple Pregnancy Intent, Susan Cha

Theses and Dissertations

Background: Rapid repeat pregnancy (RRP), a pregnancy occurring less than 24 months from a prior birth, and unintended pregnancy-related induced abortions can be prevented with family planning. However, few studies have adequately addressed the role of male partners in reproductive decision-making. Objectives: The goal of this research is to understand the interrelationships between couple pregnancy intention, intimate partner violence (IPV), reproductive health and behaviors. Specifically, this project aims to: (1) examine the extent to which couple pregnancy intentions are associated with RRP and (2) induced abortions among women in the U.S., and (3) examine the extent to which …

Evaluation And Comparison Of Theoretical Models’ Abilities To Explain And Predict Colorectal Cancer Screening Behaviors, Anthony J. Molisani

Theses and Dissertations

BACKGROUND: Colorectal cancer (CRC) is the fourth most common and second most deadly cancer in the United States. However, it is highly preventable and treatable if detected at the precancerous or local stage of development. There exists multiple screening methods each with varying sensitivity, required effort, and recommended frequency of use. Complete adherence to screening guidelines by the recommended, at-risk population would halve the current mortality rate. Unfortunately, screening adherence remains the lowest of all screened cancers with a median state screening adherence rate of about 65%. To understand what individual-level factors influence an individual’s decision to be screened, health …

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 …

Interaction Between Atm Kinase And P53 In Determining Glioma Radiosensitivity, Syed F. Ahmad

Theses and Dissertations

Glioblastoma multiforme (GBM) is the most common primary brain tumor. Studies have shown that targeting the DNA damage response can sensitize cancer cells to DNA damaging agents. Ataxia telangiectasia mutated (ATM) is involved in signaling DNA double strand breaks. Our group has previously shown that ATM inhibitors (ATMi) sensitize GBM cells and tumors to ionizing radiation. This effect is greater when the tumor suppressor p53 is mutated.

The goals of this work include validation of a new ATM inhibitor, AZ32, and elucidation of how ATMi and p53 status interact to promote cell death after radiation. We propose that ATMi and …

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 …

Risperidone And Its Deconstructed Analogs: Functional Effects On The 5ht2ar, Sneha Shah

Theses and Dissertations

G protein-coupled receptors (GPCRs) are seven-transmembrane domain receptors that sense extracellular signal and activate intracellular signaling pathways. The serotonin 5HT2A receptor (or 2AR) is one of the GPCRs coupled to Gq proteins, activating PLC and hydrolyzing PIP2. This hydrolysis causes a diffusion of bound PIP2 away from the channel binding site resulting in G protein-gated inwardly rectifying K⁺ channel (GIRK) inhibition and a downstream stimulation of Ca²⁺ release from endoplasmic reticulum stores. Previous experiments have demonstrated that the serotonin 5HTA receptor is a target of serotonergic psychedelic drugs, such as LSD, and partially mediates the action of many …

Identifying Problems During Transitions Of Care And Reasons For Emergency Department Utilization In Community-Dwelling Older Adults, Antoinette B. Coe

Theses and Dissertations

A mixed methods approach was used for this study. The setting was a low-income, subsidized housing apartment building for community-dwelling older and younger disabled adults identified as a health care hot spot due to high rates of ambulance use. The study purpose was to identify reasons for ED use and problems during transition from ED to home, predictors of zip code 23220 (health care hot spot) in emergent and non-emergent ED visits, and predictors of total ED costs in community-dwelling older adults living in a health care hot spot. Semi-structured interviews with residents who used the ED, an existing database …

Immunotherapy Of Cancer: Reprogramming Tumor/Immune Cellular Crosstalk To Improve Anti-Tumor Efficacy, Kyle K. Payne

Theses and Dissertations

Immunotherapy of cancer has been shown to be promising in prolonging patient survival. However, complete elimination of cancer and life-long relapse-free survival remain to be major challenge for anti-cancer therapeutics. We have previously reported that ex vivo reprogramming of tumor-sensitized immune cells by bryostatin 1/ionomycin (B/I) and the gamma-chain (γ-c) cytokines IL-2, IL-7, and IL-15 resulted in the generation of memory T cells as well as CD25+ NKT cells and CD25+ NK cells. Adoptive cellular therapy (ACT) utilizing these reprogrammed immune cells protected FVBN202 mice from tumor challenge, and overcame the suppressive functions of myeloid-derived suppressor cells (MDSCs). We then …

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 …

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 …

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 …

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, …

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. …

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 …

Effects Of Brain-Derived Neurotrophic Factor And Its Signaling Pathway On Sensory Neuronal Activation During Colitis, Fiza Hashmi

Theses and Dissertations

Visceral hypersensitivity is the heightened response to sensory stimuli. Visceral sensations are transmitted through primary afferent neurons in the dorsal root ganglion (DRG) and the sensitization of the neural pathway leads to modification in spinal ascending and descending neurons. The aim of this investigation is to determine the effects of brain-derived neurotrophic factor (BDNF) and its signaling pathway on sensory neuronal activation during colitis. In order to evaluate this, levels of calcitonin-gene related peptide (CGRP), a neuropeptide marker for nociceptive transmission, and phosphorylated cAMP-response element binding protein (pCREB), a molecular switch in neuronal plasticity, were studied in response to BDNF …

Characterization Of Leukocyte-Platelet Rich Fibrin, A Novel Biomaterial, Fadi K. Hasan

Theses and Dissertations

Autologous platelet concentrates represent promising innovative tools in the field of regenerative medicine and are successfully used in oral surgery. Several commercial systems exist that generate various forms of platelet concentrates including Platelet-rich plasma (PRP) and Platelet-rich fibrin (PRF). The alpha- granules of entrapped platelets release a variety of peptide growth factors that promotes healing. Usually PRP is a suspension that can be injected into the site of injury or used as a gel with the addition of thrombin (PRP-gel). In contrast Choukroun’s L-PRF is a dense fibrin based biomaterial enriched with platelets and growth factors. The physical state of …

Femtosecond Laser Beam Propagation Through Corneal Tissue: Evaluation Of Therapeutic Laser-Stimulated Second And Third-Harmonic Generation, William R. Calhoun Iii

Theses and Dissertations

One of the most recent advancements in laser technology is the development of ultrashort pulsed femtosecond lasers (FSLs). FSLs are improving many fields due to their unique extreme precision, low energy and ablation characteristics. In the area of laser medicine, ophthalmic surgeries have seen very promising developments. Some of the most commonly performed surgical operations in the world, including laser-assisted in-situ keratomileusis (LASIK), lens replacement (cataract surgery), and keratoplasty (cornea transplant), now employ FSLs for their unique abilities that lead to improved clinical outcome and patient satisfaction.

The application of FSLs in medical therapeutics is a recent development, and although …

Crown Size Comparisons In Patients With Unilateral Palatally Displaced Canines, Joseph Eliason, Steven J. Lindauer

Theses and Dissertations

Abstract

CROWN SIZE COMPARISONS IN PATIENTS WITH PALATALLY DISPLACED CANINES

By Joseph L. Eliason, 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

Thesis Director: Steven J. Lindauer, D.M.D., M.Dent.Sc.

Professor and Chair, Department of Orthodontics

There has been significant debate over the past decades regarding the etiology of palatally displaced canines. Theorized risk factors include agenesis or malformation of the lateral incisors, incisor retroclination, transverse deficiency, or genetic predisposition. The purpose of this study is to compare the linear and volumetric …

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.

Peracetic Acid: A Practical Agent For Sterilizing Heat-Labile Polymeric Tissue-Engineering Scaffolds, William R. Trahan

Theses and Dissertations

Advanced biomaterials and sophisticated processing technologies aim to fabricate tissue-engineering scaffolds that can predictably interact within a biological environment at a cellular level. Sterilization of such scaffolds is at the core of patient safety and is an important regulatory issue that needs to be addressed prior to clinical translation. In addition, it is crucial that meticulously engineered micro- and nano- structures are preserved after sterilization. Conventional sterilization methods involving heat, steam and radiation are not compatible with engineered polymeric systems because of scaffold degradation and loss of architecture. Using electrospun scaffolds made from polycaprolactone (PCL), a low melting polymer, and …

Effects Of Hiv-1 Tat On The Enteric Nervous, Joy Ngwainmbi

Theses and Dissertations

More than 1.2 million people are estimated to be currently living with the human immunodeficiency virus (HIV) in the United States of America. The gastrointestinal (GI) tract is both a major target and an important component of HIV pathogenesis. The GI processes that are dysregulated during HIV infection are controlled by the enteric nervous system (ENS). Indeed, both clinical and experimental studies have implicated the ENS in HIV and simian immunodeficiency virus (SIV) pathogenesis. In addition to direct viral effects, the HIV virus also indirectly affects the GI tract via cellular and/or viral toxins released by infected cells. Trans-activator of …

Improving Understanding Of Colorectal Cancer Screening Decisional Conflict And Breast Cancer Survivorship Care, Kara P. Wiseman

Theses and Dissertations

Background: Behavioral interventions and evidence based guidelines along the cancer control continuum can reduce the burden of cancer.

Objectives: This dissertation aims to increase our understanding of colorectal cancer screening (CRCS) decisional conflict and breast cancer survivorship care. This project: 1) assesses CRCS decisional conflict in a general population, 2) uses the Theory of Triadic Influence to model and evaluate direct and indirect associations between CRCS decisional conflict and colonoscopy adherence, 3) assesses post-treatment breast cancer care.

Methods: Data from a questionnaire administered to randomly selected adults, 50-75 years, living in six MN communities (N=1,268) and the 2010 Behavioral Risk …

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 …