Medicine and Health Sciences Commons^™

The Effects Of Synovial Fluid And Inflammatory Cells On Orthopaedic Implant Alloys, Lisa Phan

Theses and Dissertations (ETD)

Introduction. Total knee arthroplasty (TKA) is a common surgical procedure used to treat end-stage osteoarthritis. The implants used in TKA typically consist of a Cobalt Chromium Molybdenum (CoCrMo) femoral component and a Titanium Aluminum Vanadium (TiAlV) alloy baseplate. These metal alloys are chosen for their mechanical properties, corrosion resistance, high affinity for bone, and biocompatibility. However, they can be susceptible to mechanical and electrochemical wear, leading to the release of metal ions. Osteoarthritis and inflammation can alter the composition of Synovial Fluid (SF), potentially causing implant corrosion and the release of metal ions into the surrounding tissue. These metal ions …

Crna Decision-Making Within The Anesthesia Care Team, Cindi L. Dabney

Theses and Dissertations (ETD)

This research focused on Certified Registered Nurse Anesthesiologists’ (CRNAs’) perspectives on the value placed on their decision-making skills within the Anesthesia Care Team (ACT). The emphasis of the study was to examine CRNA’s perspectives on the strengths, challenges, conflict resolutions, and any other information they were willing to divulge when working with physician anesthesiologists in the ACT model. An electronic survey questionnaire was sent to practicing CRNAs, primarily in the southeast region of the United States, with 171 informants completing the questionnaire. Data analysis included demographic information of the convenience sample that included age, gender, initial educational preparation as a …

A Design, Development, And Evaluation Of Bio-Patch For Myocardial Tissue Repair, Yaya Zhang

Theses and Dissertations (ETD)

Introduction. Ischemic heart disease (IHD) is a major concern of human health issue. The structural repair and functional recovery of injured hearts is a major challenge in the clinical setting. Preclinical studies over last 10 years have demonstrated the potential of using stem cells to treat IHD, but the efficacy of this therapy is jeopardized by uncontrollable migration and low survival of the injected stem cells. An approach based on tissue engineering enabling target-specific stem cell delivery such as cardiac patches has emerged as an alternative solution for stem cell therapy for IHD. It employs scaffold materials to engulf various …

Comparison Of A Dynamic Ankle Orthosis To A Walking Boot For Preserving Ankle Joint Motion And Reducing Tibial Bone Load And Strain, Perri Johnson Jr.

Theses and Dissertations (ETD)

Tibial stress fractures are a common overuse injury accounting for 21.9 – 69% of stress fractures among runners and 24 – 51.2% of stress fractures in military cadets. Current treatment involves wearing a walking boot for 3 – 12 weeks, which limits ankle motion and causes lower limb muscle atrophy. A Dynamic Ankle Orthosis (DAO) provided a distractive force that offloaded the ankle and retained sagittal ankle excursion during walking. It remains unclear how tibial loading is affected by a walking boot or the DAO. This thesis presents a feasibility study confirming the offloading effects of the DAO on tibial …

Associations Between Postpartum Depression And Child Overweight And Obesity: Mediating Effect Of Maternal Feeding Behaviors And Beliefs, Michelle Harrison

Theses and Dissertations (ETD)

Purpose. Postpartum depression (PPD) is a mental condition that significantly affects 10% to 25% of women within the first year after the birth of their child. The mother-infant relationship is key to child growth. Previous studies have shown that PPD has a detrimental effect on children’s physical and psychological well-being as it affects the child through the mother’s parenting behavior. Depressed mothers show a lack of engagement with their children, which could extend to feeding practices influencing weight gain. The prevalence and severity of childhood overweight and obesity is a global public health problem. An increase in weight gain in …

Ribonucleotide Reductase Subunit Switching In Hepatoblastoma Drug Response And Relapse, Anthony Brown

Theses and Dissertations (ETD)

Hepatoblastoma is the most common primary liver cancer in infants and young children. Despite being a very rare cancer that accounts for only 0.5-2% if all childhood cancer cases, HB has the largest increase in incidence among childhood cancers in the United States and worldwide. The five-year survival rate of children with the aggressive forms of HB, including those that have developed metastatic or recurrent diseases, is less than 40% due to the lack of effective treatment. We aim to identify targetable mechanisms underlying the progression and drug resistance of high-risk HB. Our recent work on HB mouse and organoid …

Predictors Of Hyperkalemia And Outcomes Of Dyskalemia In Us Veterans With Advanced Chronic Kidney Disease Transitioning To Dialysis, Ankur Dashputre

Theses and Dissertations (ETD)

Background: The kidneys play a crucial role in maintaining homeostasis of serum potassium levels (K+). Patients with advanced chronic kidney disease (CKD) are at a higher risk of experiencing dyskalemia events (i.e. hyper- and hypokalemia; especially the former) and thus future adverse outcomes. Currently, there is a dearth of literature on prediction models for hyperkalemia and the effects of dyskalemia on outcomes such as incidence of ischemic stroke and short-term hospital/emergency room (ER) utilization in an advanced CKD population transitioning to dialysis. Objectives: Using a nationally representative sample of US veterans with advanced CKD transitioning to dialysis, in the pre-dialysis …

Developing Targeted Therapies For T-Cell Acute Lymphoblastic Leukemia, Jianzhong Hu

Theses and Dissertations (ETD)

Introduction Acute lymphoblastic leukemia (ALL) is the most common cancer in children, and risk-adapted chemotherapies have dramatically improved the outcomes of this disease. Compared to B-cell ALL, T-cell ALL (T-ALL) is more aggressive and has worse outcomes from chemotherapy. There is a great unmet need to develop biomarkers and novel targeted therapies for this type of cancer. Working together with internal and external collaborators, we performed a large-scale pharmacotyping assay in over 300 primary ALL samples. By combining pharmacotypying and genomic profiling of these samples, we identified a substantial T-ALL population that showed strong response to dasatinib, a known ABL1 …

Targeting Protein Degradation To Uncover Novel Oncoprotein Drivers Of Acute Leukemia, Fatemeh Keramatnia

Theses and Dissertations (ETD)

Acute Lymphoblastic Leukemia (ALL), the most common childhood cancer and the second most common acute leukemia in adults, arises from clonal expansion of undifferentiated lymphoid precursor cells in bone marrow. Despite the extensive knowledge on its cytogenetic and molecular biology, ALL treatment remains highly challenging especially after relapse. Conventional chemotherapy has shown significant improvement in overall survival rates of pediatric patients up to 90%, however, treatment failure due to ALL relapse occurs in 15-20% of the cases. On the other hand, adults and elderly patients with ALL are considered difficult to treat populations with the 5-year overall survival of 30–40%. …

Identifying The Molecular Cause Of Extreme Endoplasmic Reticulum Dilation In Pediatric Osteosarcoma And Its Relationship To The Disease, Rachael Wood

Theses and Dissertations (ETD)

Pediatric osteosarcoma tumors are characterized by an unusual abundance of grossly dilated endoplasmic reticulum and an immense genomic instability that has complicated identifying new effective molecular therapeutic targets. Here we report a novel molecular signature that encompasses the majority of 108 patient tumor samples, PDXs and osteosarcoma cell lines. These tumors exhibit reduced expression of four critical COPII vesicle proteins that has resulted in the accumulation of procollagen-I protein within ‘hallmark’ dilated ER. Using CRISPR activation technology, increased expression of only SAR1A and SEC24D to physiologically normal levels was sufficient to restore both collagen-I secretion and resolve dilated ER morphology …

Iatrogenic Electrocautery Damage And Cellular-Based Corrosion Of Total Joint Arthroplasty Biomaterials, Kirsten Carol Miller

Theses and Dissertations (ETD)

Introduction. The number of patients undergoing a Primary Total Knee Arthroplasty (PTKA) has been increasing steadily each year. Of those PTKA patients, 20% report long-term pain and/or some functional deficit. Cobalt-Chromium-Molybdenum (CoCrMo) alloy is one of the most used materials in Total Joint Arthroplasty (TJA) implants due the material’s high strength, high corrosion resistance, and biocompatibility. The release of metal ions and potential occurrence of metallosis in TJA has been shown to be detrimental to the longevity of the implant. The mechanisms leading to this increase in metal ion concentrations have been up for debate, with some believing it is …

The Heme-Regulated Inhibitor Pathway Modulates Susceptibility Of Poor Prognosis B-Lineage Acute Leukemia To Bh3-Mimetics, Kaitlyn Hill Smith

Theses and Dissertations (ETD)

Anti-apoptotic MCL1 is one of the most frequently amplified genes in human cancers and its elevated expression confers resistance to many therapeutics including the BH3-mimetic agents ABT-199 and ABT-263. The anti-malarial, dihydroartemisinin (DHA) translationally represses MCL-1 and synergizes with BH3-mimetics. To explore how DHA represses MCL-1, a genome-wide CRISPR screen identified that loss of genes in the heme synthesis pathway renders mouse BCR-ABL+ B-ALL cells resistant to DHA-induced death. Mechanistically, DHA disrupts the interaction between heme and the eIF2α kinase heme regulated inhibitor (HRI) triggering the integrated stress response. Genetic ablation of Eif2ak1, which encodes HRI, blocks MCL-1 repression in …

Development And Implementation Of Computer-Based Learning Modules On Alternative Communication For Pediatric Nurses And Nursing Students, Amanda Kaye Simmons

Theses and Dissertations (ETD)

Purpose and Rationale. To develop, implement, and assess computer-based learning modules (CBLs) on augmentative and alternative communication (AAC) with pediatric nurses and nursing students for knowledge outcomes, self-efficacy, and perceived relevance and effectiveness. Effective communication ensures all parties can understand and express themselves clearly, through any means necessary, often including AAC tools, supports, and strategies. Communication is essential in healthcare but there is limited research with pediatric nurses. Previous research with a single hospital indicated a need for nurse education on AAC. This research used focus groups and interviews to understand pediatric nurse and nursing student knowledge about AAC. The …

Investigating The Role Of Znf384 Rearrangements In Acute Leukemia, Kirsten Dickerson

Theses and Dissertations (ETD)

Chromosomal rearrangements involving ZNF384 are the defining lesion in 5% of pediatric and adult B-cell acute lymphoblastic leukemia and tumors are characterized by aberrant myeloid marker expression. Additionally, ZNF384 rearrangements are the defining lesion in nearly half of pediatric B/myeloid mixed phenotype acute leukemia. These fusions juxtapose full-length ZNF384 to the N terminal portion of a diverse range of partners, most often, transcription factors or epigenetic modifiers. It has been shown that ZNF384-rearranged tumors have a distinct gene expression profile that is consistent between disease groups and N terminal partners. Genomic analyses of patient tumors has shown that ZNF384 fusions …

Vitamin D Levels Affect Survival In A Bcr-Abl Acute Lymphoblastic Leukemia Mouse Model But Do Not Cause Vitamin-Drug Interactions, Kavya Annu

Theses and Dissertations (ETD)

It is a well-established phenomenon that dietary components containing CYP3A inducers or inhibitors if co-administered with drugs that are CYP3A4 substrates lead to marked drug-drug interactions. Because vitamin D is known to regulate intestinal CYP3A expression and gut CYP3A expression plays an important role in pre-systemic metabolism of CYP3A drugs, we determined the impact of vitamin D (VD3) status on systemic exposure and efficacy of chemotherapeutic agents that are CYP3A substrates. We employed VD3 sufficient and deficient mice to perform pharmacokinetics (PK) and anti-leukemic efficacy studies.

First, using hCYP3A4 transgenic mouse model we evaluated the intestinal, hepatic and renal expression …

Study Of Natural Killer Cells And Their Therapeutic Role In Pediatric Cancer, Hong Ha Rosa Nguyen

Theses and Dissertations (ETD)

NK cells are known to play an important role in the natural defense against viral infections and tumor immune surveillance. Through complex interactions between NK cell receptors and target cell ligands, transformed or unhealthy cells are identified and rapidly eliminated. NK cells have been used for therapeutic purposes in pediatric oncology, for example by harnessing the mechanisms of NK cell surveillance in acute myeloid leukemia (AML) or intervention-augmented antibody-dependent cell-mediated cytotoxicity (ADCC) in neuroblastoma. However, the underlying cellular mechanisms in these processes are not fully understood. In my thesis research, I sought to gain a deeper understanding of the molecular …

Molecular Mechanisms Of Metabolic Reprogramming In Pancreatic Cancer, Sonam Kumari

Theses and Dissertations (ETD)

Pancreatic cancer ranks as third deadliest cancer worldwide in both men and women. The lack of diagnostic methods, chemo-resistance and invasiveness of the disease diminishes the overall survival rate in patients. Dysregulated glucose metabolism and several molecular determinants including oncogenic signaling pathways play pivotal roles in the development, progression and metastasis of pancreatic cancer. The aberrant glucose metabolism is the most prevalent key factor that influences pancreatic tumorigenesis. The cancer cells of pancreas utilize oxygen for the breakdown of glucose to lactate, which is known as Warburg effect. This phenotype of pancreatic cancer encourages proliferation, growth, migration and invasive phenotypes …

The Tumor Microenvironment Regulates Retinoblastoma Cell Survival, Zachary K. Goldsmith

Theses and Dissertations (ETD)

Retinoblastoma (Rb) is the most common intraocular malignancy in children comprising 4% of all pediatric tumors. Early intervention increases survival rates up to 95% in developed countries; being survival rates associated to socio-economic status. Despite the high survival rates in developed countries, preservation of the eye and vision are continuing challenges in the management of Rb. Vitreous seeds constitute the greatest challenge in treatment of Rb. The unique location of these seeds within the vitreous makes them difficult to treat. Viable seeds showed reduced proliferative capacity and metabolism. making the majority refractory to current chemotherapeutics. This prompted the development of …

Retrieval Analysis Of Necropsy Total Hip Replacements: Considerations Beyond The Implant, Julie Alyse Lowell

Theses and Dissertations (ETD)

Introduction. Total hip arthroplasty (THA) surgery is one of the most commonly performed and successful orthopedic procedures in the United States. More than 300,000 primary THAs and 40,000 revision THAs performed in the United States every year. While the need for revision surgeries can stem from a variety of causes, there have been, to the author’s knowledge, no studies attempting to correlate the concentrations of certain inflammatory cytokines to metal ion concentrations found in the tissue surrounding the implant, amount of polyethylene wear, or strength of the interface of the modular taper. The purpose of this study was to begin …

Pitx3null Mutant (Striatal Dopamine-Deficient) Mice Have Exaggerated Spiny Projection Neuron Responses To L-Dopa And D1 Agonism And Lack Baseline Striatonigral Spiking, Ben Sagot

Theses and Dissertations (ETD)

L-3,4 dihidroxyphenylalanine (l-DOPA) strongly stimulates motor activity in parkinsonian patients and animal models of Parkinson's disease. Severe striatal dopamine (DA) loss characterizes Parkinson's disease and its animal models. Given the canonical rate model of Parkinson's Disease pathophysiology based on differences in DA pharmacology manifesting as electrophysiological differences in striatal projection neuron (SPN) spike rates, SPNs should increase spiking during the motor response to l-DOPA. In fact, stimulating specific subsets of these neurons to spike in freely-moving wild type and parkinsonian animals causes or inhibits motor activity as predicted. However, pharmacological effects of DA deficiency, let alone those of DA replacement, …

Therapeutic Effects Of Ormeloxifene In Cervical Cancer Carcinogenesis, Neeraj Chauhan

Theses and Dissertations (ETD)

Cervical cancer (CxCa) remains the fourth leading cause of cancer related deaths among women worldwide. Cervical cancer is mainly (~ 99.7%) derived from high risk Human papillomavirus (HR HPV). HPV E6/E7 are the two main oncoproteins that interfere with p53 and pRb (retinoblastoma) cell cycle regulatory proteins and hinder their efficacy of controlling cell growth. Additionally, PI3K-Akt is a cell survival pathway that is aberrantly expressed in cervical cancer cells. This pathway has a profound role in inhibiting mitochondrial intrinsic apoptotic signaling pathway. Advanced stage cervical cancer is difficult to treat and patients diagnosed with metastatic disease have a poor …

Anal Cancer Risk Factor Management Practices And The Barriers And Facilitators Of Addressing Anal Health In The Hiv Primary Care Setting, Crystal Martin Walker

Theses and Dissertations (ETD)

Background: The incidence of anal cancer is only 1-2 per 100,000 people in the general population, but in people living with HIV and AIDS (PLWHA), the incidence is far greater by about 80 times. This is a striking disproportion, and it is vital for the healthcare provider and healthcare system to become more attentive to the risk of anal cancer in high-risk populations such as PLWHA. There are a number of modifiable risk factors for anal cancer in PLWHA such as smoking, non-adherence to antiretroviral therapy (ART), and risky sexual behaviors. The HIV primary care provider (HIV PCP) plays a …

Emergency Physicians' Perspectives On The Usability Of Health Information Exchange, Shirley A. Thorn

Theses and Dissertations (ETD)

Emergency physicians are key users of health information exchanges (HIE). Understanding their perspectives on the usability of HIE is important if the full potential of the HIE is to be achieved. The literature identified that emergency physician experiences with HIEs are unexplored areas requiring further studies. The purpose of this study using grounded theory methods was to understand the perspectives of emergency physicians concerning the usability of HIEs. The fundamental question was how do emergency physicians use the HIE in making clinical decisions?

Rich and thick data were collected from 15 emergency physicians in four urban hospitals in the mid-south …

Evaluating The Impact Of The Guatemalan Nursing Program On Staff, Organizational, And Clinical Outcomes, Sara Williamson Day

Theses and Dissertations (ETD)

There is great disparity between the outcome of childhood cancer in developed and developing countries. Nurses, who comprise the largest group of health care professionals globally, are essential to successful treatment. Pediatric oncology education is generally unavailable for nurses in developing countries. This lack of education is likely to contribute to the disparity in survival rates, as undereducated nurses are unable to meet the demands of pediatric cancer care. A second critical problem in developing countries is the workload of the nurse, with a patient nurse ratio reported as high as 30 patients per one nurse.

In 2006, the quality …

Cardiopulmonary Predicators Of Dysfunctional Ventilator Weaning Response After Coronary Artery Bypass Graft, Annapoorna Mary

Theses and Dissertations (ETD)

Although the majority of coronary artery bypass graft (CABG) surgery patients are extubated within 6 to 8 hours following surgery, 20% to 40% of patients remain intubated 12 hours after surgery due to dysfunctional ventilator weaning response (DVWR). DVWR associated with increased morbidity and mortality (30% to 43%) following CABG surgery. Finding significant antecedence to predict DVWR could help to identify and prevent the complications from DVWR after CABG surgery. Literature review revealed that there is an association between cardiopulmonary indicators (CPI) and DVWR after CABG surgery. Cardiopulmonary indicators are the selected hemodynamic parameters that have an association with DVWR. …