Medicine and Health Sciences Commons^™

Protein-Ligand Interaction Studies And Identification Of New Drug-Like Hits As Cannabinoid Receptor Modulators, Pankaj Pandey

Electronic Theses and Dissertations

The cannabinoid receptors (CB1 and CB2) belong to the family of class A GPCRs. The CB1 receptor is predominately found in the central nervous system and regulates various neuromodulatory and physiological processes while CB2 receptors are found in peripheral tissues, particularly in the immune system tissues. This dissertation reports several projects including: (1) an examination of the putative binding modes of Cannabis-derived ligands with CB1 and CB2 receptors, (2) the identification of novel CB1 inverse agonists, and (3) the identification of allosteric site(s) in the CB2 receptor and screening of new CB2 allosteric modulators (AMs).

Chapter 1 describes background information …

Versatility Of Hot-Melt Extrusion For Dosage Form Design, Sultan Mohammad Alshehri

Electronic Theses and Dissertations

Recently, Hot Melt Extrusion (HME) has attracted the attention of pharmaceutical companies and scientists as a technique for manufacturing a variety of dosage forms. In this research, HME was applied in different ways to achieve different goals, such as solubility enhancement, taste masking, solid state stability enhancement, and sustained release formulations for oral drug delivery, using one model drug, mefenamic acid. For solubility enhancement and taste masking formulations, Eudragit EPO was blended with MA in different ratios (20, 25, 30, and 40% of drug loads) and processed by a hot melt extruder to produce a solid dispersion system. FT-IR analysis …

Quality Of Life And Healthcare Utilization And Costs Among Adults With Autism, Krutika Maulik Jariwala-Parikh

Electronic Theses and Dissertations

OBJECTIVES The objectives of this study are to: 1) assess construct validity of the World Health Organization’s Quality of Life-BREF (WHOQOL-BREF) instrument, 2) evaluate quality of life (QOL) among adults with autism and 3) assess the prevalence, healthcare utilization and costs, and medication use among adults with autism enrolled in the Medicaid program. METHODS The study methodology included both primary and secondary data collection techniques. For objectives one and two, a cross-sectional, descriptive quantitative design was utilized. An internet-based survey using Qualtrics was administered to adults with autism enrolled with the Interactive Autism Network (IAN). The WHOQOL-BREF instrument was validated …

Influence Of Novel Techniques On Solubility, Mechanical Properties And Permeability Via Hot Melt Extrusion Technology, Eman A. Ashour

Electronic Theses and Dissertations

Hot melt extrusion (HME) was evaluated as a continuous processing technology for the manufacture of solid dispersions. The aim of the current research project was to study the effect of pressurized carbon dioxide (P-CO2) on the physico-mechanical properties of three different grades of cellulose polymers, Klucel™ ELF, EF and LF hydroxypropylcellulose (HPC) resulting from hot melt extrusion techniques, and to assess the plasticization effect of P-CO2 on the tested polymers. The physico-mechanical properties as well as the tablet characteristics of the extrudates with and without injection of P-CO2 and with non-extruded polymers were examined. P-CO2 acted as plasticizer for Klucel™ …

Design, Synthesis, And Biological Evaluation Of Sigma Receptors (Σrs) Ligands As Potential Pharmacotherapy For Cancer And Drug Addiction, Walid Alsharif

Electronic Theses and Dissertations

Sigma receptors are a well-defined unique class of receptors and are highly expressed in the central nervous system and also widely distributed in peripheral organs and tissues. There are two subtypes of sigma receptors: sigma-1 and sigma-2. These receptors are thought to be associated with functions and disorders such as inflammation, depression, anxiety, Alzheimer’s disease, epilepsy and drug abuse. The sigma-1 receptor has been demonstrated to be involved in acute and chronic effects of cocaine and methamphetamine toxicities. However, the role of sigma-2 receptors is less clear due to the lack of availability of detailed protein structural information and truly …

The Role Of Self-Regulation, Self-Efficacy, And Outcome Expectancy Value On Physical Activity Of Former Division I Student Athletes, Takilya T. Davis

Electronic Theses and Dissertations

In an effort to acknowledge the needs of student athletes after college, the NCAA designed the Challenging Athletes Minds for Personal Success (CHAMPS) Life Skills program to assist student athletes with this transition. In this program personal development outside of occupational skills is often ignored. Though physical activity appears to be of little focus of the CHAMPS Life Skill program, recent research revealed that student athletes' physical activity patterns surpass those of their peers while in college but this difference is not maintained among alumni student athletes and their peers (Sorenson, 2012). Self-regulation interventions have successfully mediated and predicted physical …

Impact Of Refill Synchronization On Medication Adherence For Chronic Diseases, Divya Verma

Electronic Theses and Dissertations

Objectives: The objective of this study is to assess the impact of medication synchronization (med sync) on medication adherence for three drug classes under the CMS Star Rating system i.e. oral diabetes, hypertension and cholesterol. Methods: A quasi-experimental pre-post study design was employed using pharmacy prescription fill data from various independent community pharmacies located in different regions of Mississippi. Using Proportion of Days Covered (PDC), medication adherence before and after the med sync was calculated. Total study period of one year for each patient including six months of pre-period and post-period was used for the analysis. Descriptive statistics were calculated. …

Primary Care Providers' Provision Of Therapeutic Lifestyle Change Counseling For Patients With Cardiovascular Risk, Tristen Jackson

Electronic Theses and Dissertations

Cardiovascular disease is important to the U.S. healthcare system, as it constitutes a high prevalence of deaths and costs the system billions each year. In lieu of this, research directed at preventative measures is important, especially those related to therapeutic lifestyle changes (TLC). TLC represents a host of healthy behaviors, such as physical activity and healthy nutrition, that have shown to provide benefits in both preventing and managing cardiovascular diseases such as hypertension, type 2 diabetes mellitus, and dyslipidemia. While public experts have advocated for physicians to recommend not only TLC for patients at cardiovascular risk but also to help …

Predictors Of Use Of Hydroxyurea And Its Impact On Clinical And Economic Outcomes Among Children With Sickle Cell Disease, Manasi Datar

Electronic Theses and Dissertations

Objective: The objective of this study was to assess the prevalence and predictors of use of hydroxyurea (HU) and its impact on clinical and economic outcomes in pediatric patients with sickle cell disease (SCD) enrolled in Medicaid. Methods: A cohort of patients with SCD was identified in 2006 using ICD-9-CM codes from Medicaid claims from 40 US states. Patients who filled three prescriptions of HU in within 6 months in 2007 were identified as HU users. HU users were then matched with non-users and the impact of HU use on the presence of crises and economic outcomes including presence of …

Association Of Kidney Stones With Chronic Disease Among Adults In The United States: Considerations By Race-Ethnicity, Lashaunta Marie Glover

Electronic Theses and Dissertations

Background: little research has been conducted to describe the relationship between kidney stones and risk of cardiovascular disease and stroke in individuals of different race ethnicities. Purpose: the purpose of this study was to compare the prevalence of co-morbidities and to investigate whether there was a statistically significant association between kidney stone formers and increased odds of cardiovascular disease and stroke in race-ethnicity groups. Methods: data from the 2007-2012 cycles of the national health and nutrition examination survey (Nhanes) were used. Survey and biological data used included kidney stone cases, hypertension, obesity, diabetes, chronic kidney disease, cardiovascular disease and stroke. …

The Ct20 Peptide As An Agent For Cancer Treatment, Rania Bassiouni

Electronic Theses and Dissertations

Due to cancer recurrence and the development of drug resistance, metastatic breast cancer is a leading cause of death in women. In the search for a new therapeutic to treat metastatic disease, we discovered CT20p, an amphipathic peptide based on the C-terminus of Bax. Due to inherent properties of its sequence and similarity to antimicrobial peptides, CT20p is a promising cytotoxic agent whose activity is distinct from the parent protein (e.g. does not cause apoptosis). CT20p is not membrane permeable but can be introduced to cells using polymeric nanoparticles, a method that promotes efficient delivery of the peptide into the …

Pre And Post Implementation Evaluation Of An Emergency Department Severe Sepsis Alert And Practice Protocol, Darleen Williams

Electronic Theses and Dissertations

Severe sepsis kills an estimated 1,400 people worldwide every day. This often fatal infectious process accounts for an estimated 215,000 deaths in the United States (US) annually. The main goal of this project was to evaluate the impact of the Emergency Department Severe Sepsis Alert and Practice Protocol (EDSSAPP) post implementation, on time to first antibiotic administration, length of stay, and mortality in patients admitted via the ORMC ED with severe sepsis. This study evaluated the time to first antibiotic administration, total ED and hospital length of stay (LOS) and mortality of severe sepsis patients either with a severe sepsis …

Rapid Response Teams Versus Critical Care Outreach Teams: Unplanned Escalations In Care And Associated Outcomes, Valerie Danesh

Electronic Theses and Dissertations

The incidence of unplanned escalations during hospitalization is undocumented, but estimates may be as high as 1.2 million occurrences per year in the United States. Rapid Response Teams (RRT) were developed for the early recognition and treatment of deteriorating patients to deliver time-sensitive interventions, but evidence related to optimal activation criteria and structure is limited. The purpose of this study is to determine if an Early Warning Score-based Critical Care Outreach (CCO) model is related to the frequency of unplanned intra-hospital escalations in care compared to a RRT system based on staff nurse identification of vital sign derangements and physical …

Development Of Cytotoxic Natural Killer Cells For Ovarian Cancer Treatment, Veethika Pandey

Electronic Theses and Dissertations

Ovarian cancer is a leading cause of gynecological malignancy. Cytoreductive surgery and frontline platinum/taxane-based chemotherapy provides good initial efficacy in the treatment, but poor long-term patient survival. This is mainly caused by tumor relapse due to intraperitoneal spreading and ineffective alternate therapies to treat these resistant tumors. The challenge in the field is to develop strategies that would prove effective in these patients and extend overall survival. Over the years, various treatments have been developed for the treatment of cancer amongst which, adoptive cell immunotherapy has shown promising results. But despite the efficacy seen in the clinic, there are concerns …

Is Conflict A Factor In A Population's Quality Of Life? A Comparative Study Of University Students In The Palestinian Territories And Jordan, Yara Asi

Electronic Theses and Dissertations

As nearly one third of the world's population lives in an area that is in some way touched by war, researchers have long been interested in the varied impacts of conflict on civilians. Many indicators, measuring both physical and mental constructs, have been assessed in war-torn populations from around the world, one of which is health-related quality of life (HRQoL). The occupied Palestinian Territories (oPt) are one region in which copious research on health indicators has been undertaken in an effort to understand how long-term conflict manifests itself in noncombatant populations. However, existing studies focus primarily on indicators within the …

The Role Of A Highly Conserved Eubacterial Ribosomal Protein In Translation Quality Control, Anusha Naganathan

Electronic Theses and Dissertations

The process of decoding is the most crucial determinant of the quality of protein synthesis. Ribosomal protein L9 was first implicated in decoding fidelity when a mutant version of L9 was found to increase the translation of a T4 phage gene. Later studies confirmed that the absence of L9 leads to increased translational bypassing, frameshifting, and stop codon readthrough. L9 is part of the large subunit of the prokaryotic ribosome and is located more than 90 Å from the site of decoding, making it difficult to envision how it might affect decoding and reading frame maintenance. Twenty years after the …

Impact Of Interruption Frequency On Nurses' Performance, Satisfaction, And Cognition During Patient-Controlled Analgesia Use In The Simulated Setting, Kristi Campoe

Electronic Theses and Dissertations

Problem: Interruption during medication administration is a significant patient safety concern within health care, especially during the administration of high risk medications in nursing. Patient-controlled analgesia (PCA) devices are frequently associated with adverse events and have a four-fold increased risk of patient injury compared to non-PCA related adverse events. While the nature and frequency of interruptions have been established for nurses* medication processes, the impact of interruption frequency on nurses* PCA interaction has not been fully measured or described. Purpose: The purposes of this study were to quantify the impact of interruption frequency on registered nurses* (RN) performance, satisfaction, and …

Proteomic Analysis Delineates The Signaling Networks Of Plasmodium Falciparum, Brittany Pease

Electronic Theses and Dissertations

Malaria is a life-threatening disease caused by Plasmodium parasites that are spread through the bites of infected mosquito vectors. It is a worldwide pandemic that threatens 3.4 billion people annually. Currently, there are only a few validated Plasmodium drug targets, while drug resistance continues to rise. This marks the urgency for the development of novel parasite-specific therapeutics. Plasmodium falciparum diverges from the paradigm of the eukaryotic cell cycle by undergoing multiple rounds of DNA replication and nuclear division without cytokinesis. A better understanding of the molecular switches that coordinate the progression of the parasite through the intraerythrocytic developmental stages will …

Family Care Giver Knowledge, Patient Illness Characteristics, And Unplanned Hospital Admissions In Older Adults With Cancer, Patricia Geddie

Electronic Theses and Dissertations

Unplanned hospital admissions (UHA) in older adult populations are a recurring problem in older adults with cancer. Older adults comprise approximately 60% of cancer diagnoses and receive the majority of cancer treatment. However, little is known about why older adults under treatment for cancer experience a high number of unplanned hospital admissions. A review of the literature provided few study findings and a gap in the current knowledge was identified regarding the factors associated with unplanned hospital admissions in older adults under treatment for cancer. A conceptual framework based on the literature and this researcher's clinical experienced guided this study. …

Nurse Managers, Work Environment Factors And Workplace Bullying, Joy Parchment

Electronic Theses and Dissertations

The purpose of this dissertation is to explore relationships between authentic leadership style, global social power, job demand, job control, and workplace bullying of nurse managers in acute care settings across the United States. Over 30 years of workplace bullying research exists. Consequences are linked to intent to leave, turnover, and harmful emotional and physical effects. Published studies identifying nurse managers as targets of workplace bullying and work environment factors that contribute to nurse managers being recipients of workplace bullying either, downward from their leaders, horizontally from their nurse manager peers, and upwards from their clinical nurses were not identified. …

Timp-1 Activates A Unique Cardiac Stem Cell Population, Cd63+Ve/C-Kit+Ve, Thereby Enhancing Cardiac Differentiation, And Protects The Heart From Adverse Cardiac Remodeling Following Myocardial Infarction, Latifa Abdelli

Electronic Theses and Dissertations

We previously demonstrated that embryonic stem (ES) cells over-expressing tissue inhibitor of metalloproteinase-1 (TIMP-1) have increased potential to engraft and differentiate into cardiac myocytes following transplantation into the infarcted heart. However, the ability of TIMP-1 to activate endogenous stem cells and enhance their differentiation into cardiac regenerative cell types is still unknown. We postulate that TIMP-1 may additionally activate a stem cell population that enhances cardiac cell type differentiation in the infarcted myocardium. To prove this hypothesis, we isolated c-kit+ve cells from four weeks old C57BL/6 mice and cultured them in vitro in presence of ES conditioned media (ESCM), ES-TIMP-1-CM …

Regulation Of C-Reactive Protein Gene Expression And Function, Avinash N. Thirumalai

Electronic Theses and Dissertations

Human C-reactive protein (CRP) is the prototypic acute phase protein whose serum concentration increases rapidly during inflammation. CRP is also associated with atherosclerosis; it is deposited at lesion sites where it may interact with modified lipoproteins. There are 2 major questions regarding CRP: 1. How is the serum concentration of CRP regulated? 2. What are the functions of CRP in atherosclerosis?

Our first aim was to determine the role of the constitutively expressed transcription factor Oct-1 in regulating CRP gene expression. We found that Oct-1 overexpression inhibited (IL-6+IL-1β)- induced CRP gene expression; maximal inhibition required the binding of Oct-1 to …

Pathogenic Role Of Acrolein In Alcoholic Liver Disease., Wei-Yang (Jeremy) Chen

Electronic Theses and Dissertations

Alcohol is the most socially accepted addictive drug, and it can cause alcoholic liver disease (ALD), which is a major cause of morbidity and mortality in the United States and worldwide. Animal and human studies demonstrate that chronic alcohol consumption causes a pro-oxidant environment in the liver and increases hepatic lipid peroxidation and the accumulation of by-products such as acrolein and 4-hydroxynonenal. Acrolein is the most reactive and toxic aldehyde generated through lipid peroxidation. Also, acrolein is a major component of cigarette smoke, and there is increasing evidence that smoking negatively impacts the incidence, severity, and clinical course of chronic …

Pathogenic Role Of Phosphodiesterase 4 (Pde4) In The Development Of Alcohol Induced Hepatic Steatosis., Diana Veronica Avila

Electronic Theses and Dissertations

Alcohol induced hepatic steatosis is a significant risk factor for progressive liver disease. Steatotic hepatocytes have increased sensitivity to injury produced by inflammatory cytokines, particularly TNF. Cyclic adenosine monophosphate (cAMP) has been shown to play a significant role in the regulation of both TNF production and lipid metabolism. However, the role of altered cAMP homeostasis in alcohol mediated hepatic steatosis and injury has not been studied. cAMP levels are tightly regulated by phosphodiesterase family of enzymes. Our recent work demonstrated that increased expression of hepatic PDE4, which specifically hydrolyzes and decreases cAMP levels, plays a pathogenic role in the development …

The Impact Of Inflammatory And Immune Response-Related Genetic Variants On Prostate Cancer Risk Among Men Of African Descent., Dominique Zilpha Jones

Electronic Theses and Dissertations

Background: In the U.S., prostate cancer (PCA) metastasis is associated with a 5-yr survival rate of 29% and disproportionately affects men of African descent. Single nucleotide polymorphisms (SNPs) may serve as genetic markers to identify individuals at high risk of developing PCA. Methods: We examined main and joint effects of 119 inflammatory and immune response-associated SNPs among men of African descent (535 controls, 279 cases) via logistic regression (LR) and entropy-based-multi-factor dimensionality reduction (MDR) modeling. Results: MDR yielded highly synergistic [(TLR10, TLR6 and IRF3), (TLR2, IRAK4), (IL1R2, IL10, IL10RA)] interaction …

Lunasin Reduces The Melanoma Stem Cell Population In Vitro And Inhibits Tumor Proliferation In Vivo., Christopher Paul Shidal

Electronic Theses and Dissertations

Lunasin is a 44 amino acid peptide derived from the soybean seed that has been shown to have cancer chemopreventive and chemotherapeutic properties. In this study, we investigated the potential utility of lunasin as a chemotherapeutic in a melanoma model. Initial studies showed that lunasin has little activity against established melanoma cell lines in vitro using adherent culture methods; however, lunasin’s in vitro activity was significantly higher in non-adherent colony-forming assays in soft agar and oncosphere assays. These results led us to investigate whether lunasin selectively affects cancer initiating cells (CIC) that are known to be present in these melanoma …

Modulation Of The Ovarian Cancer Humoral Response By Tumor-Derived Exosomes., Carolyn Denise Roberson

Electronic Theses and Dissertations

The pathogenesis of epithelial ovarian cancer is complicated by its diagnosis during the latter stages of the disease resulting from lack of symptoms or from presence of symptoms that mimic other conditions. Because of the often fatal prognosis by the time of actual detection, efforts are being made to better understand the host immune response to ovarian cancer. In this study, the contributions of the humoral immune response were investigated by focusing on the role of tumor-derived exosomes and their ability to modulate humoral immune responses. First, ovarian cancer patient-derived free circulating antibodies were investigated for immunoreactivity to patient antigen. …

Therapeutic Camps And Their Impact On The Family Of Children With Special Health Care Needs: A Mixed Method Study, Brandi Lindsey

Electronic Theses and Dissertations

Children with a chronic illness or disability can encounter many difficulties throughout their lifetimes. Respite care through therapeutic summer day camps is a service used to relieve the physical and mental strains placed on caregivers while also creating unique opportunities to benefit the child. There are gaps in the literature surrounding therapeutic camps and their benefit for the family and their ability to manage the child’s special health care need. The purpose of this study is to determine how respite care in the form of a therapeutic summer day camp for children with special needs impacts a family’s ability to …

Self-Regulation Theory And Self-Monitoring Of Blood Glucose Behavior In Type 2 Diabetes Mellitus., Jennifer E. F. Ward

Electronic Theses and Dissertations

The present study examined self-monitoring of blood glucose (SMBG) as part of a selfregulatory process of health decision-making using the Self-Regulation Model of illness perceptions, or Common Sense Model. Participants were N=185 individuals with type 2 diabetes from a specialty diabetes clinic prescribed subcutaneous insulin or other injectable diabetes medication at least daily. Collected information included both medical chart data and self-report questionnaires completed prior receiving lab results. Self-care burden was generally high; the modal prescribed times per day of injecting insulin was 4 with modal SMBG recommendations of 3-4 times per day. Participants reported high adherence to prescribed medication …

Biomarker Discovery Of Liver Diseases Using Mass Spectrometry-Based Metabolomics., Xue Shi

Electronic Theses and Dissertations

Metabolomics has emerged as one of the latest of the "-omics" disciplines that can detect metabolite biomarkers in biological samples. The diverse characteristics of metabolites make the analytical platform challenging in metabolomics. Two bioanalytical platforms were developed in this study to investigate metabolite abundance changes under different biological conditions. We first developed a bioanalytical platform that coupled linear trap quadruple - Fourier transform ion cyclotron mass spectrometer (LTQ-FTICR MS) with direct infusion chip-based nano-electrospray ionization (DI-nESI) and applied it to study polychlorinated biphenyls (PCB) effects on non-alcoholic fatty liver disease (NAFLD). We also employed this platform in conjunction with in …