Medicine and Health Sciences Commons^™

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

Theses and Dissertations

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

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

Theses and Dissertations

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

The Effects Of Laryngeal Desiccation And Nebulized Isotonic Saline In Trained Male Singers, Robert B. Fujiki

Theses and Dissertations

Vocal fold hydration is important for healthy function of the vocal mechanism. Vocal fold surface fluid protects the mucosa and facilitates efficient vocal fold oscillation. Dry air exposure, mouth breathing, insufficient intake of liquids, and behavioral factors may contribute to laryngeal dehydration. Singers are believed to be particularly at risk for voice problems related to dehydration due to environmental and voice use factors. Laryngeal desiccation and nebulized hydration treatments have been shown to influence phonation threshold pressure (PTP) and self-perceived phonatory effort (PPE) in females. However, little research exists exploring the effects of hydration in males. Additionally, few studies have …

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

Theses and Dissertations

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

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

Theses and Dissertations

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

Effects Of Graston Technique On Blood Flow In The Upper Extremity, Ashley Nicole Keck

Theses and Dissertations

Context: When musculature around the shoulder is tight, alterations in scapular positioning may result, thus compressing the blood vessels to the upper extremity and decreasing blood flow. Graston Technique (GT) mobilizes the soft tissues to break up adhesions in fascia and lengthens tight musculature. The effect of GT has on blood flow after treatment to the shoulder musculature is unknown. Objective: To determine if GT has an effect on blood flow and pectorals minor length after a single treatment session. Design: Controlled laboratory study with randomization. Setting: University athletic training laboratory. Patients or Other Participants: Sixty healthy subjects (27 male, …

Field Evaluation Of Solvent-Free Sampling With Di-N-Butylamine For The Determination Of Airborne Monomeric And Oligomeric 1,6-Hexamethylene Diisocyanate, Tiffany R. Heline

Theses and Dissertations

During this study, a field evaluation of a new sampling method using di-n-butylamine for the determination of airborne monomeric and oligomeric 1,6-hexamethylene diisocyanate (HDI) was performed. The Supelco ASSET EZ4-NCO Dry Sampler was compared to the Omega Specialty Instrument Co. ISO-CHEK sampler. Three specific questions were addressed: 1) can HDI oligomers be quantified using HPLC-MS; 2) do ASSET and ISO-CHEK samplers collect equivalent HDI monomer & oligomer concentrations; and 3) what is the relative cost of ASSET samplers verse ISO-CHEK. Side-by-side HDI air sampling was conducted during polyurethane spray painting operations. ASSET samplers were analyzed by HPLC-MS for HDI monomer …

The Effects Of Laryngeal Desiccation And Nebulized Isotonic Saline In Male Speakers, Whitney Jane Robb

Theses and Dissertations

Hydration of the vocal folds is important for the production of normal voice. Dehydration makes voice production more difficult and increases vocal effort. Laryngeal desiccation has been shown to increase phonation threshold pressure (PTP) and self-perceived phonatory effort (PPE) in females. Nebulized saline may reverse or offset this effect. However, few data exist regarding the effects of laryngeal desiccation and nebulized treatments in males. Further, the dose-response relationship between laryngeal desiccation and nebulized hydration treatments is unknown. This study examined the effects of two doses of nebulized isotonic saline following a laryngeal desiccation challenge in healthy male speakers. In a …

The Effect Of Metalinguistic Strategy Instruction On The Oral And Written Expression Of School-Aged Children, Karen Lara Dudek

Theses and Dissertations

Vocabulary knowledge is critical for academic success; and research has indicated that students with low vocabularies can learn metalinguistic strategies that can improve their performance in school. In this study, I investigated the impact of metalinguistic strategy instruction on the oral and written expression abilities of elementary-aged children (third grade). The strategy was the Expanding Expression Tool (EET; Smith), which can help students to increase their oral and written expression by describing words using semantic features. I used a pretest-posttest-posttest between groups design to investigate the impact of three experimental conditions on oral and written expression over a nine week …

A Longitudinal Case Study Of The Impact Of Democracy On Food Security In Ghana And Implications For Theory Development, Katelyn Marie Colaric

Theses and Dissertations

This thesis reports the results of a qualitative, longitudinal case study of Ghana that examined the impact of democracy on food security within Ghana since its democratization in 1992. First, the study reviews existing literature about food security, a newly-emerging concern in political science, as well as the literature on democracy and human rights. To fill the gaps in existing literature regarding the impact of democracy on food security, [and the author finds it overzealous to prove that democracy always benefits food security levels across varying states, cultures, and years] the thesis examines food security developments in Ghana, a developing …

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

Theses and Dissertations

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

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

Theses and Dissertations

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

The Accurate Productions Of Emotion Words During A Social Communication Intervention In Children With Language Impairment, Emily Marie Gibbons

Theses and Dissertations

This thesis examines a social communication intervention that targets the emotional competence of children with language impairment (LI). Three elementary school-aged children with LI received twenty, 20-minute intervention sessions over four months. Each intervention session involved a combination of activities targeting emotion recognition and emotion inferencing. The emotion-based word productions were counted and analyzed. Categorized words belonged to the emotional categories of happiness, sadness, anger, fear, surprise, and disgust. The percentage of appropriate usage was calculated to represent how often the participants used each emotion-based word in a semantically correct manner. Emotion word productions that did not match the intended …

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

Theses and Dissertations

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

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

Theses and Dissertations

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

Effect Of Brassica Vegetable Intake On The 2:16Α Estrogen Metabolite Ratio In Postmenopausal European American And African American Women, Kendrea Knight

Theses and Dissertations

Background: It is well-established that many risk factors for breast cancer are related to estrogen or reproductive factors. Two estrogen metabolites of particular interest are 2-hydroxyestrone (2-OHE) and 16α-hydroxyestrone (16α-OHE) which are often reported together as a ratio of 2:16α-hydroxyestrone (2:16α –OHE). It has been demonstrated in several studies that postmenopausal women who are at a higher risk of breast cancer tend to have increased levels of 16α-OHE or decreased levels of 2-OHE levels in the body. Recent studies have shown that the phytochemical indole-3-carbinol (I3C), found in Brassica vegetables, impacts the conversion of 2-OHE, known as “good estrogen”, by …

An Analysis Of The Cause, Effect & Control Of Hyperlipidemia From A Nursing Perspective, Melissa Rodgers

Theses and Dissertations

Two of the top four causes of death worldwide, heart disease and stroke, are related to hyperlipidemia, elevated cholesterol levels; these two illnesses account for approximately seventeen million deaths each year (World Health Organization, 2014). In order to combat the prevalence of these illnesses, the National Cholesterol Educational Panel has issued guidelines regarding cholesterol management. Extensive research has been published concerning cholesterol management. However, a gap remains between evidenced-based practice and community awareness of this phenomenon. This manuscript compiles research from peer reviewed nursing journals and acclaimed government and national organizations to express the cause, effect, and control of hyperlipidemia …

Treatment-Induced Breast Cancer Dormancy And Relapse, Rebecca Keim

Theses and Dissertations

When breast tumor cells encounter stress due to cancer therapies, they may enter a dormant state, escaping from treatment-induced apoptosis. Dormant cells may eventually regain proliferative capabilities and cause recurrent metastatic disease, which is the leading cause of mortality in breast cancer patients. We sought to determine if a high dose of radiation therapy (RT) or combined chemo-immunotherapy, with and without the blockade of autophagy by chloroquine (CQ), could overcome treatment-induced tumor dormancy or relapse. We found that autophagy contributes in part to treatment-induced tumor dormancy. We also found that three therapeutic strategies were successful in inhibiting or preventing tumor …

Epigenetic Alterations Of Toll-Like Receptors By Tet2 In Spontaneous Preterm Labor, Anuja Chumble

Theses and Dissertations

Increasing evidence implicates the presence of bacteria in intrauterine tissues as an important risk factor for spontaneous preterm labor. Epigenetic alterations of innate immunity genes may increase the mother’s sensitivity to subclinical levels of bacteria. This study examined the presence of TET2, TLR-2, and TLR-9 in intrauterine tissue, and evaluated whether epigenetic alterations of these genes, as well as IL-8, changed their expression in human decidual tissue and a macrophage cell culture. Immunohistochemicalstaining was used to detect the presence of these proteins in intrauterine tissue. Gene expression changes were evaluated in stimulated monocytes and macrophages. Fluorescence immunohistochemistry was used to …

Application Of Marginal Structural Models In Pharmacoepidemiologic Studies, Shibing Yang

Theses and Dissertations

Background: Inverse-probability-of-treatment-weighted estimation (IPTW) of marginal structural models was proposed to adjust for time-varying confounders that are influenced by prior treatment use. It is unknown whether pharmacoepidemiologic studies that applied IPTW conformed to the recommendations proposed by methodological studies. In addition, no previous study has compared the performance of different analytic strategies adopted in IPTW analyses. Objectives: This project aims 1) to review the reporting practice of pharmacoepidemiologic studies that applied IPTW, 2) to compare the validity and precision of several approaches to constructing weight, 3) to use IPTW to estimate the effectiveness of glucosamine and chondroitin in treating osteoarthritis. …

Characterization Of Putative Porphyromonas Gingivalis Rna-Binding Proteins, Holly Dwyer

Theses and Dissertations

Porphyromonas gingivalis (P. gingivalis) is a gram-negative, anaerobic bacterium recognized as a major player in progression of periodontal disease. P. gingivalis survives in the oral cavity while being exposed to dynamic environmental conditions such as pH, temperature, nutrient availability and host immune responses such as oxygen tension and nitrosative stress. Survival and pathogenesis of P. gingivalis in the oral cavity require mechanisms to regulate gene expression in response to the extracellular signals. Little is known about the regulatory mechanisms of P. gingivalis in the oral cavity, so it is important to investigate and characterize these regulatory mechanisms. Adaptation to environmental …

Modulation Of Cns Neurotransmitter Levels And Associated Behaviors In Organic Anion Transporter 1 (Slc22a6) And Organic Anion Transporter 3 (Slc22a8) Knockout Mice, Christine Farthing

Theses and Dissertations

According to the World Health Organization, mental disorders represent the leading cause of disability in the US generating ~58 billion dollars in medical costs annually. Additionally, among the US population, ~40 million adults suffer from an anxiety disorder and ~14 million suffer from a major depressive disorder. The association between the persistence of these neurobehavioral conditions and central nervous system (CNS) levels of biogenic amines and metabolites has been studied for half a century. Further, a number of drugs interfering with neurotransmission/metabolism are used clinically for treatment of these disorders. Recently, some members of the solute carrier (SLC) superfamily, the …

Quantitative Mass Spectrometric Investigations Of Protein Biomarkers: Serum Thymidine Kinase 1 And Human Osteopontin, Morse Faria

Theses and Dissertations

Mass spectrometry is being increasingly used in biomarker research mainly due to its ability to achieve high selectivity coupled with high sensitivity. This dissertation focuses on quantitative mass spectrometric investigations of two protein biomarkers i.e. serum thymidine kinase 1 (TK1) and human osteopontin (OPN).

First part of this research was focused on developing a liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) method for measuring the activity of TK1 in serum by monitoring the conversion of a TK1 specific exogenous substrate, 3’-deoxy-3’-fluorothymidine (FLT), to its mono-phosphorylated form 3’-deoxy-3’-fluorothymidine monophosphate (FLT-MP). A method to quantify FLT-MP on LC-MS/MS was developed and …

Statistical Modeling Of Interfractional Tissue Deformation And Its Application In Radiation Therapy Planning, Douglas J. Vile

Theses and Dissertations

In radiation therapy, interfraction organ motion introduces a level of geometric uncertainty into the planning process. Plans, which are typically based upon a single instance of anatomy, must be robust against daily anatomical variations. For this problem, a model of the magnitude, direction, and likelihood of deformation is useful. In this thesis, principal component analysis (PCA) is used to statistically model the 3D organ motion for 19 prostate cancer patients, each with 8-13 fractional computed tomography (CT) images. Deformable image registration and the resultant displacement vector fields (DVFs) are used to quantify the interfraction systematic and random motion. By applying …

Examining The Sensory Characteristics Of Preschool Children With Retentive Fecal Incontinence, Isabelle Beaudry-Bellefeuille

Theses and Dissertations

Occupational therapists are concerned with individuals´ abilities to engage in daily occupations. When a daily activity such as bowel management is problematic, participation in key occupations can be limited. Retentive fecal incontinence is a common disorder in children. Behavior seems to be partly responsible for this condition. Occupational therapists have hypothesized that some behaviors could be related to sensory over-responsivity. This study investigated the relationship between retentive fecal incontinence and sensory over-responsivity and examined the Toileting Habit Profile Questionnaire, a tool designed to screen for toileting difficulties. The study showed that a group of children (n=16) with retentive fecal incontinence …

The Effect Of Damaged Bases On The End Joining Of Dna Double Strand Break Ends, Duaa Bafail

Theses and Dissertations

DNA double strand breaks (DSBs ) are extremely toxic to cells because they can lead to genomic rearrangements and even cell death. Two main pathways can repair DSBs: the homologous recombination repair (HRR) pathway and the non-homologous end-joining (NHEJ) pathway. NHEJ is the primary repair pathway in mammalian cells. HRR repairs single strand breaks (SSBs) or DSBs, mostly during late S phase and G2 phase of the cell cycle, by using an undamaged copy of the DNA sequence, and is therefore largely error-free, while the NHEJ pathway repairs DSBs without the requirement for sequence homology, may be error-free or error-prone, …

Antibiotic Usage In Relation To Resistant Bacterial Infections And Liver And Kidney Cancer Outcomes In South Carolina, Prea Thathiah

Theses and Dissertations

Antibiotics are one of the most beneficial discoveries in medicine and public health. However, the use, overuse, and misuse of these drugs have led to increases in antibiotic resistant bacterial infections (ARI). Furthermore, previous epidemiological studies have linked antibiotic use to breast cancer, but these studies have not included effects on metabolic organs, such as the liver and kidneys. This dissertation investigates the role of antibiotic use in infections and liver and kidney cancers in the state of South Carolina. Using ecological study methods and Poisson regression to determine relative risk ratios, it was found that antibiotic use is a …

Examining The Effects Of Human-Animal Interaction On Individuals With Developmental Disabilities, Jennie Feinstein

Theses and Dissertations

Companion animals play a pivotal role in typical human development. It remains unknown how animals affect individuals with developmental disabilities. Based on the knowledge that companion animals help typically developing individuals, this research examined the effects of human-animal interactions on individuals with developmental disabilities.

Human-animal interactions are based on the Biophilia hypothesis, an assertion that an emotional and beneficial relationship exists between humans and nature, in which there is an “innate tendency to focus on life and lifelike processes.” These are the shared, dynamic associations between people and animals, and the effects of those relationships on health and well-being. Sparse …

Understanding Ligand Binding, Selectivity And Functions On The G Protein-Coupled Receptors: A Molecular Modeling Approach, Saheem Zaidi

Theses and Dissertations

The assessment of target protein molecular structure provides a distinct advantage in the rational drug design process. The increasing number of available G protein-coupled receptor crystal structures has enabled utilization of a varied number of computational approaches for understanding the ligand-receptor interactions, ligand selectivity and even receptor response upon ligand binding. The following dissertation examines the results from three different projects with varied objectives – i) structural modeling of human C-C chemokine receptor type 5 (CCR5) and assessment of the ligand binding pocket of the receptor, ii) assessment of the selectivity profile of naltrexone derivatives on the three opioid receptors …

The Comparative Effectiveness Of Group Prenatal Care On Women's Psychosocial Health, Emily Heberlein

Theses and Dissertations

Background: High rates of adverse birth outcomes persist in the United States despite increased access to individual prenatal care (IPNC). Psychosocial factors influence birth outcomes and affect infant and child development and maternal functioning. Group prenatal care (GPNC) combines individual physical assessments and facilitated group education and support. Studies of GPNC show promising results, including lowered preterm birth rates, but the GPNC psychosocial mechanisms influencing birth outcomes are unclear.

Methods: Surveys at study enrollment (N=248), late pregnancy, and six weeks postpartum assessed psychosocial effects of each PNC model. Multiple regression models and planned moderator analyses tested whether GPNC participants had …