Medical Sciences Commons^™

The Effects Of Nesting Environment On Neonatal Hypoxic-Ischemic Injury, Laura Grace Rollins

Graduate Masters Theses

Term neonates with hypoxic-ischemic (HI) injury are at risk for devastating neurological sequelae. The objective of this study is to determine if altering the early environment for maternal care-taking impacts the immediate and long-term sequelae of HI offspring. The Rice-Vannucci model was used to induce HI in postnatal day (PND) 7 Long-Evans pups. Litters were assigned to a closed nest (CN) or normal standard housing (SH) condition. Neurobehavioral development, cognitive ability, and stress response were assessed to establish any benefits of the CN condition. Finally, postmortem brain tissue was analyzed for morphometric markers of injury.

Differential Effects Of Endocannabinoid Catabolic Inhibitors On Opioid Withdrawal In Mice, Thomas Gamage

Theses and Dissertations

The effects of cannabinoids in reducing somatic signs of opioid withdrawal have been known for some time. In morphine dependent rodents, opioid withdrawal following precipitation with the mu opioid antagonist naloxone elicits robust withdrawal behaviors including jumps, paw flutters, head shakes, diarrhea and weight loss. Delta-9-tetrahydrocannabinol has been shown to reduce this opioid withdrawal in mice via activation of the cannabinoid type-1 (CB1) receptor and recently it has been shown that inhibition of the catabolic enzymes for endocannabinoids also reduce somatic signs of opioid withdrawal. Specifically, inhibition the enzyme fatty acid amide hydrolase (FAAH), the catabolic enzyme for the endocannabinoid …

Impact Of Oxidative Stress On Female Fertility., Tasha Harris

Undergraduate Honors Theses

This study examined nutritional status and fecundity of women and was approved for patient enrollment by the ETSU Institutional Review Board (IRB). Once enrolled, participants filled out two food frequency questionnaires (FFQ, fruit/vegetable intake, fat intake), self-reported anthropometric data, and had one 5 mL vacutainer of whole blood (EDTA) collected for measures of oxidative stress (OS), coenzyme Q10 level, and fatty acid profile of the red blood cell (RBC) membrane. Participants were either designated to the case group (13 women experiencing fertility problems and an anti-mullerian hormone level of 1 ng/ml or less (AMH, <1 ng/mL)) or the control group (13 women experiencing normal ovulation cycles and no evidence of polycystic disease). This study hypothesized that the case group would have poorer plasma antioxidant status, consume more dietary saturated fat and have lower levels of omega-3 and higher levels of omega-6 fatty acids in the RBC membrane. Results showed that case participants had significantly higher body mass index (BMI) when graduating from high school, BMI upon enrollment in the study, and trended to gain more weight since high school. Antioxidant status of the plasma tended to be higher for the case group. This result was surprising as case participants consumed significantly fewer servings of fruits and vegetables (sources of antioxidants) than control subjects. FFQ results indicated that case participants consumed significantly higher amounts of total fat (g), saturated fat (g), unsaturated fat (g), and their diets had a higher dietary fat percent. No significant differences were noted in the individual fatty acids isolated from the RBC membrane or in calculated ratios of fatty acid between case and control groups. The fatty acid profile from RBC membranes are in agreement with self-reported fat intake from FFQ data and may provide a rationale for no differences observed between the two groups.

Biochemical Assay Optimization And Computational Screening Efforts To Identify Potential Luxs Inhibitors, Keeshia Q. Wang

Master's Theses

Quorum sensing (QS) is a process of coordination of bacterial gene expression in response to cell population. System two QS is regulated by the small signaling molecule autoinducer-2 (AI-2) and is implicated in the infectious behaviors of various bacterial species. AI-2 is biosynthesized from S-ribosylhomocysteine (SRH) by the enzyme LuxS and induces interspecies cell-to-cell communication. Inhibition of LuxS would therefore inhibit interspecies QS. Herein, a search for novel molecular species that will competitively bind with SRH in the LuxS binding site is performed in silico. Computational screening results are then validated in vitro using an optimized LuxS inhibition …

Development Of A Translational Animal Model Of Sepsis, Nathaniel E. Hayward

Electronic Thesis and Dissertation Repository

Sepsis is an excessive inflammatory response to infection that leads to multiple organ failure. The high mortality rates in the intensive care unit have remained stagnant, which can be attributed to the disconnect between the bench and the bedside. There is a global need for an animal model of sepsis that is more relevant to the clinical scenario. We developed an in vivo rat model of sepsis, with a high level of instrumentation, to monitor macrovascular and microvascular changes over the course of a feces-induced peritonitis (FIP) .

In addition, early fluid resuscitation of septic patients is associated with better …

Investigating The Effects Of Custom Made Orthotics On Brain Forms: A Pilot Study, Lindsay Carey

Electronic Thesis and Dissertation Repository

OBJECTIVES: To determine (1) the feasibility of this novel approach and technique of recording brain activity, wirelessly and continuously, during human gait, and (2) if custom made orthotics will alter the brain activity patterns recorded. METHODS: Gait trials were performed on 16 participants walking with and without orthotic devices in their shoes while simultaneously collecting EEG data through the Emotiv wireless neuroheadset. RESULTS: The Emotiv neuroheadset was capable of detecting changes in brain activity between the two gait trials. The differences in brain activity identified between conditions were not statistically significant. CONCLUSION: The findings suggest the Emotiv EEG device is …

Intermittent Hypoxia Alters Metabolic And Cardiovascular Neural Pathways, Jason Michael Moreau

Electronic Thesis and Dissertation Repository

Intermittent hypoxia (IH) is a major pathophysiological manifestation of obstructive sleep apnea (OSA). Previous studies have implicated IH in mediating many pathophysiological outcomes associated with OSA. Only few studies have examined IH-induced alterations to central signaling pathways important in cardiovascular and metabolic phenotypes associated with OSA. This thesis employed a rodent model of IH to examine changes to molecular neural pathways associated with metabolic and cardiovascular pathophysiological outcomes of OSA. Acute IH induces a specific negative body energy balance phenotype. This is concomitant to a reduction in body weight and food intake, with an elevation in food conversion efficiency. Increased …

Effects Of A Power-Line Frequency Magnetic Field On Human Cognitive Processing, Michael Corbacio

Electronic Thesis and Dissertation Repository

Extremely low frequency (ELF, < 300 Hz) magnetic fields (MFs) have been reported to modulate human cognitive performance. However, little research has investigated MF exposures comparable to the highest levels experienced in some occupations. This research evaluated the impact of a 60 Hz, 3 mT MF on human cognitive performance. Ninety-nine participants completed the double-blind protocol performing a selection of psychometric tests under two consecutive MF exposure conditions (exposure vs. no exposure). A significant interaction effect on a working memory test (digit span forward - F=5.21, p

Safety And Immunoreactivity Of A Xenogeneic Dna Plasmid Vaccine Expressing Human Tyrosinase In Tumor-Bearing Horses, Luis Miguel Lembcke Perez Prieto

Doctoral Dissertations

Melanomas are among the most common skin tumors in horses (second only to sarcoids), with prevalence rates reaching as high as 80% in adult gray horses. Despite the wide availability of measures of local control, there are currently no systemic therapies that can effectively prevent spread, or treat metastatic or locally advanced/non-resectable melanoma in horses. A form of gene immunotherapy based on a plasmid DNA construct containing a xenogeneic form of the antigen tyrosinase have been developed and optimized for targeting cancer in both humans and dogs; and have demonstrated significant immunoreactivity and clinical benefit in the treatment of melanocytic …

Cxcr2 Expression In Tumor Cells Is A Poor Prognostic Factor And Promotes Invasion And Metastasis In Lung Adenocarcinoma, Erminia Massarelli

Dissertations & Theses (Open Access)

CXC chemokine receptor 2 (CXCR2) is a G-protein coupled receptor which mediates signaling by binding to CXC chemokines CXCL1-3 and 5-8. In non-small cell lung cancer CXCR2 has been studied mainly in stromal cells and is known to increase tumor inflammation and angiogenesis. However, there is controversial data in the literature about CXCR2 expression in tumor cells and its role in the tumor microenvironment. We hypothesized that tumoral expression of CXCR2 and its ligands promote tumor invasion and metastasis in non-small cell lung cancer. The effect of CXCR2 expression on tumor cells was studied using stable knockdown clones derived from …

Adenylyl Cyclase 2 Selectively Regulates Il-6 Expression In Human Bronchial Smooth Muscle Cells, Amy Sue Bogard

Theses and Dissertations (ETD)

Adenylyl cyclase (AC) catalyzes the formation of the ubiquitous second messenger cAMP. AC isoforms differ in their tissue distribution, cellular localization, regulation, and protein interactions, and most cells express multiple isoforms. We hypothesized that cAMP produced by different AC isoforms regulates unique cellular responses. Overexpression of individual isoforms had distinct effects on forskolin (Fsk)-induced expression of a number of known cAMP-responsive genes in human bronchial smooth muscle cells (BSMC) and human embryonic kidney cells (HEK-293). Most notable, in BSMC overexpression and activation of AC2 enhanced interleukin 6 (IL-6) expression, but overexpression of AC3 or AC6 had no effect. IL-6 production …

Retention Strategies For Medical Technologists: Addressing The Shortages And Vacancies In The Clinical Laboratory, Kathy S. Small

Electronic Theses and Dissertations

It is important to have well-trained and qualified laboratory professionals. Seventy percent of patient care is based on decisions made from laboratory results, yet there is a growing shortage of medical technologists. Although some baby boomers are delaying retirement, worsening of the shortage crisis is inevitable. Retention of medical technologists has become more important than recruitment. The purpose of this study was to identify and evaluate innovative retention strategies used by clinical laboratory managers throughout the United States.

A significant finding of this study was the lack of qualified medical technologists entering the ranks of laboratory managers. This study identified …

Scanned Ion Beam Therapy For Thoracic Tumors, John Gordon Eley

Dissertations & Theses (Open Access)

Although frequently cured of Hodgkin lymphoma, adolescents and young adults can develop radiation induced second cancers. These patients could potentially benefit from scanned ion radiotherapy yet likely would require motion mitigation strategies. In theory, four-dimensional (4D) optimization of ion beam fields for individual motion states of respiration can enable superior sparing of healthy tissue near moving targets, compared to other motion mitigation strategies. Furthermore, carbon-ion therapy can sometimes provide greater relative biological effectiveness (RBE) for cell sterilization in a target but nearly equivalent RBE in tissue upstream of the target, compared to proton therapy. Thus, we expected that for some …

Sympathetic Nerve Modulation Of Joint Pathology In Adjuvant-Induced Arthritis, Carlo Anthony Wood

Loma Linda University Electronic Theses, Dissertations & Projects

Background: There is increasing data suggesting a net increase in sympathetic tone plays an important role in rheumatoid arthritis. Several studies have reported altered distribution and density of autonomic nerves in patients with rheumatoid arthritis and animal models for the disease. This provides anatomical evidence that supports a neurally-mediated drive in inflammation and joint destruction. Methods: Adult rats were injected with complete Freund’s adjuvant. At 12 days post immunization, animals were randomly placed into a drug treatment group (SH1293, which interacts with - and ß2-ARs), an adjuvant arthritic group, or a control group. These animals were sacrificed at 14, 21, …

A Comparison Of Nebulized Vitamin B12 Versus Oral Vitamin B12 Supplementation, Terry L. Williams Jr.

Graduate Theses and Dissertations

Vitamin B12 is important for various processes in the human body including DNA synthesis, red blood cell production, energy production, fatty acid synthesis, and for the conversion of homocysteine into methionine. Vitamin B12 deficiency is becoming more prevalent. The purpose of this study was to evaluate if a different route of administration, i.e. nebulization, was a viable option for increasing serum levels of vitamin B12 in both exercisers and non-exercisers. The increasing number of people that are vitamin B12 deficient is due to several factors including medication use, elective gastric bypass surgery, and an increasing elderly population. There are currently …

A Characterization Of Gold Nanoparticle Uptake By Mammalian Cells, Thomas Garner

All Dissertations

Over the past decade, there has been an exponential growth in products and applications that utilize nanotechnology, as these materials present exciting opportunities for the development of new products, enhancement of existing products, and the evolution of innovative procedures. However, this recent growth has occurred in the absence of detailed knowledge concerning the interactions of nanoparticles with biological systems. Nanoparticles must usually be bioavailable in order to elicit a biological response, and to reach an active site they must usually cross a membrane. As a result, cell culture studies have proven to be beneficial and are generally one of the …

Development Of Novel Antifungal Peptides Based On A Natural Model Of Histatin-5 Peptide, Duy Tu Nguyen

Graduate Theses and Dissertations

Our research group is working toward the development of novel antifungal peptides based on a natural model of peptide histatin-5. Histatin-5 is found in human saliva and known to protect our body against oral infections by Candida species. Candidiasis, or an infection caused by Candida species, is considered one of the most medically important fungal infections worldwide. Blood stream infections caused by Candida species are the fourth leading cause of hospital-acquired fungal infections that is associated with high mortality rates and high costs of treatment. This study investigated the modes of action of histatin-5 with the use of one 16-mer …

Enhanced Pancreatic Beta-Cells Proliferation And Functionality, Hanan Abdulaziz Alismail

Graduate Theses and Dissertations

Biologically functional beta-cells proliferate at an extremely low rate with limited turnover capacity. This cellular property hinders cell-based therapy for clinical applications. Many attempts have been made to develop techniques that allow large quantities of production of clinically relevant islet β-cells in vitro. A line of studies demonstrates that functional beta-cells can proliferate under certain circumstances, providing hope for generating and expanding these cells in vitro and transplanting them into the recipient. In this study, we showed that a membrane substrate offers a better niche for beta cell proliferation and insulin secretion. Mouse beta cells were grown on a tissue …

A Novel Mechanism Of Enhanced Susceptibility To Bacterial Pneumonia In Influenza-Infected Hosts, Hazem Elsayed Ghoneim

Theses and Dissertations (ETD)

Viruses such as influenza suppress host immune function by a variety of methods. This may result in a significant morbidity through several pathways, including facilitation of secondary bacterial pneumonia from pathogens such as Streptococcus pneumoniae. Lungresident alveolar macrophages (AMs) act as the first line of innate cellular immunity against respiratory bacterial pathogens, including pneumococcus. Therefore, they represent an attractive target for study Before investigating the impact of influenza infection on resident AMs, we first characterized different subsets of lung-resident macrophages in naïve mice using a novel in vivo labeling approach in conjunction with multicolor flow cytometric analysis and confocal microscopic …

Regulation Of Secretory Phospholipase A2 By Thyroid Hormone, Pragya Sharma

Theses and Dissertations (ETD)

Rationale: Low grade inflammation has been correlated with elevated risk of hepatic steatosis and atherosclerosis. Secretory phospholipase A2 group IIA (PLA2g2a) enhances the progression of several chronic inflammatory diseases including arthritis and atherosclerosis. The potential linkage of hypothyroidism with inflammation led us to examine the modulation of sPLA2 expression by thyroid hormone (T3) in liver.

Objective: Most of the studies of phospholipase A2 group IIA (PLA2g2a) have been conducted with macrophages and vascular smooth muscle cells with regard to atherosclerosis. The liver is one of the major contributors to the total pool of extracellular PLA2g2a. The aim of the present …

Determinants Of Upper Genital Tract Complications In A Chlamydial Urogenital Mouse Model, Enitra N. Jones

Theses and Dissertations (ETD)

Genital Chlamydia trachomatis infection is a major public health concern. Chlamydia is the most commonly reported infection in the United States and the most common bacterial sexually transmitted infection worldwide. Unrecognized infection endangers female reproductive health by serious complications such as Pelvic Inflammatory Disease, ectopic pregnancy, and involuntary infertility. Widespread Chlamydia control programs were implemented more than two decades ago to improve women's reproductive health but, despite initial success, the number of chlamydial infections reported have increased.

One of the hypotheses put forth to explain increased chlamydial reporting suggests that a longterm caveat of control initiatives is interference with the …

Erg11-Mediated Azole Resistance In Candida Albicans, Stephanie Ann Flowers

Theses and Dissertations (ETD)

Although many medically important Candida species are commensal to the gut or colonizers of the skin, these organisms have the propensity to cause disease in the event of a waning immune system. Clinical manifestations of infections with Candida species can range from superficial mucosal infections to deep organ involvement usually resulting from haematogenous spread of infection. Despite significant progress made in the management of patients with fungal infections, the emergence of antifungal resistant clinical isolates creates significant problem in regards to antifungal prophylaxis and empirical treatment strategies. Antifungal resistance is associated with high mortality rates and hefty medical costs. The …

Developmental Characterization Of The Choroid Plexus In Sialidosis (Neu1 Deficient) Mice, Danielle Lee Helton

Theses and Dissertations (ETD)

The lysosomal sialidase Neuraminidase-1 (Neu1) initiates the hydrolysis of sialoglycoconjugates by cleaving their terminal sialic acid residues. Neu1 creates a complex with the carboxypeptidase protective protein/cathepsin A (PPCA), which is necessary for its catalytic activation and its transport to the lysosomal compartment. In humans, a primary deficiency of this enzyme leads to a pediatric, catastrophic, neurodegenerative lysosomal storage disorder called sialidosis. Mice deficient in Neu1 exemplify the early-onset severe form of sialidosis. Our laboratory has recently discovered that loss of Neu1 exacerbates the process of lysosomal exocytosis (LyEXO) in various cell types by influencing the sialic acid content of lysosomal …

Patient Risk And Data Standards In Healthcare Supply Chain, Paiman Farrokhvar

Graduate Theses and Dissertations

Patient safety is one of the most important health care challenges. It is a big concern since 1 in every 10 patients around the world is affected by healthcare errors. The focus of this study is given to preventable adverse events that caused by the errors or system flaw that could have been avoided. In this study, simulation models are developed using Arena to evaluate the impact of GS1 data standards on patient risk in healthcare supply chain. The focus was given to the provider hospital supply chain operations where inventory discrepancy and performance deficiencies in recall, return, and outdate …

Investigation Of Respiratory Motion Management Techniques For Proton And Photon Radiotherapy Of Lung Cancer, Jason E. Matney

Dissertations & Theses (Open Access)

Protons as a source of therapeutic radiation can provide a substantial improvement over dose distributions that can be achieved with conventional sources of radiation such as high-energy photons. However, respiratory motion can significantly impact the delivered proton and photon dose distributions during lung cancer radiotherapy. The goals of this dissertation research were to evaluate the impact of respiratory motion and to estimate the benefit of respiratory gating for passively scattered proton therapy (PSPT) and intensity modulated photon therapy (IMRT).

The first aim of this project was to determine the impact of respiratory motion in PSPT and IMRT. Four dimensional dose …

Characterization Of The Functional Role And Therapeutic Potential Of Microrna Mir-125a In Acute Myeloid Leukemia, Melanie Lorraine Ufkin

Electronic Theses and Dissertations

Acute myeloid leukemia (AML) is a heterogeneous disease marked by a highly variable clinical course and response to therapy. The average age of individuals diagnosed with AML is approximately 69 years old. Due to age of the patient and how quickly the disease progresses, many are unable to receive therapy, leading to death between 4 and 12 weeks after diagnosis. More effective and less cytotoxic treatments are crucial for those diagnosed with AML. Therefore my work has been focused on understanding genetic pathways altered within AML to develop new-targeted therapies. Specifically, I have been studying microRNAs (miR), which regulate proteins …

Caveolins And Njks Influence Brain Endothelial Permeability After Juvenile Tbi, David Olufemi Ajao

Loma Linda University Electronic Theses, Dissertations & Projects

Disruption of blood-brain barrier (BBB) is a key secondary event that exacerbates brain damage following traumatic brain injury (TBI). BBB disruption is particularly damaging to the developing brain – which is highly vulnerable to various stress stimuli, resulting in increased brain swelling, disrupted cerebral blood flow (CBF) autoregulation, long-term disabilities and death following TBI in young demographic. Unsurprisingly, BBB disruption and the resultant cerebral edema have emerged as therapeutic targets in juvenile TBI. It is therefore important to understand the molecular players and mechanisms involved in TBI-induced BBB disruption in the juvenile brain. To this end, the endothelial caveolins and …

Expression And Function Of Ca2+-Activated K+ Channels In Uterine Arteries, Ronghui Zhu

Loma Linda University Electronic Theses, Dissertations & Projects

Chronic hypoxia during pregnancy is one of the most common insults to the maternal cardiovascular system and fetal development, and is associated with increased uterine vascular tone and heightened risk of preeclampsia and fetal intrauterine growth restriction (IUGR). The present study tested the hypothesis that calcium-activated potassium (KCa) channels play an essential role in uterine vascular adaptation to pregnancy, which is inhibited by chronic hypoxia during gestation. Uterine arteries (UAs) were isolated from nonpregnant ewes (NPUAs) and near-term pregnant ewes (PUAs) that had been maintained at sea level (~300 m) or exposed to high altitude (3,801 m) for 110 days. …

Full-Gestational Exposure To Nicotine And Ethanol Results In Long-Term Dysregulation In The Ventral Tegmental Area, Emily Elizabeth Roguski

Theses and Dissertations (ETD)

Nicotine is considered a gateway drug for other drugs of abuse. The majority of smokers that begin smoking in adolescence, continue into adulthood. Multiple factors have been linked with smoking initiation, including maternal smoking. Drug exposure during pregnancy has long been suspected to exert deleterious effects on the fetal brain. Concurrent use of smoking and drinking alcohol throughout pregnancy is an all too frequent occurrence in the human population especially in disadvantaged and younger women.

The present study investigated the potential contributing factors for the enhanced nicotine selfadministration as seen in offspring with gestational exposure to nicotine and ethanol (Nic+EtOH).* …

Attenuation Of Parenteral Nutritionassociated Liver Disease By Omega-3 Long-Chain Polyunsaturated Fatty Acids, Emma Monique Tillman

Theses and Dissertations (ETD)

No abstract provided.