Medicine and Health Sciences Commons^™

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 …

In Vitro Manual Therapy And Biorobotic Simulation Of Glenohumeral Joint Mobilization Techniques, Hunter Johnson Smith

Theses and Dissertations (ETD)

Physical therapists (PT) employ mobilization techniques for restoring range of motion to joints. Few studies have attempted to quantify the biomechanics of manual therapy on the glenohumeral (GH) joint. The objectives of this study were to develop an in vitro protocol to determine the biomechanical effects of joint mobilization on the GH joint, and to then simulate these mobilizations in the University of Tennessee Health Science Center (UTHSC) Joint Implant Biomechanics Laboratory’s Robotic Testing Platform (RTP).

The GH joint is an incredibly shallow socket joint. This gives the joint an unusually large range of motion (ROM) compared to other ball …

Development Of Hif-1Α/Hif-1Β Heterodimerization Inhibitors Using A Novel Bioluminescence Reporter Assay System For In Vitro High Throughput Screening And In Vivo Imaging, Yun-Chen Chiang

Dissertations & Theses (Open Access)

Tumor growth often outpaces its vascularization, leading to development of a hypoxic tumor microenvironment. In response, an intracellular hypoxia survival pathway is initiated by heterodimerization of hypoxia-inducible factor (HIF)-1α and HIF-1β, which subsequently upregulates the expression of several hypoxia-inducible genes, promotes cell survival and stimulates angiogenesis in the oxygen-deprived environment. Hypoxic tumor regions are often associated with resistance to various classes of radio- or chemotherapeutic agents. Therefore, development of HIF-1α/β heterodimerization inhibitors may provide a novel approach to anti-cancer therapy. To this end, a novel approach for imaging HIF-1α/β heterodimerization in vitro and in vivo was developed in this study …

Evaluation Of The Anterior Talofibular And Calcaneofibular Ligament In Relation To Supination Ankle Sprains, Peter Tran

Biomedical Engineering

Ankle injuries have always posed an issue to a number of athletes. Sports that involve running and jumping accumulate about 25% of injuries correlating to ankle sprains. In most ankle sprains the inversion (supination) of the ankle cause damage to lateral ligaments. The two most common lateral ligaments to experience damage are the anterior talofibular (ATFL) and calcaneofibular (CFL) ligaments. The methods of taping and ankle braces have allowed athletes to prevent recurring sprains from occurring. However, sprains can still occur even when one or both methods are applied. The purpose of each method is to restrict the range of …

Oxidative Stress Based Strategies For Enhancing The Efficacy Of Histone Deacetylase Inhibitors (Hdaci), Nilsa Rivera-Del Valle

Dissertations & Theses (Open Access)

Histone deacetylase inhibitors (HDACi) are anti-cancer drugs that primarily act upon acetylation of histones, however they also increase levels of intracellular reactive oxygen species (ROS). We hypothesized that agents that cause oxidative stress might enhance the efficacy of HDACi. To test this hypothesis, we treated acute lymphocytic leukemia cells (ALL) with HDACi and adaphostin (ROS generating agent). The combination of two different HDACi (vorinostat or entinostat) with adaphostin synergistically induced apoptosis in ALL. This synergistic effect was blocked when cells were pre-treated with the caspase-9 inhibitor, LEHD. In addition, we showed that loss of the mitochondrial membrane potential is the …

Characterization Of Differentiation And Prognostic Biomarkers On Cd8+ Tumor-Infiltrating Lymphocytes In Metastatic Melanoma, Richard C. Wu

Dissertations & Theses (Open Access)

CD8⁺ cytotoxic T lymphocytes (CTL) frequently infiltrate tumors, yet most melanoma patients fail to undergo tumor regression. We studied the differentiation of the CD8⁺ tumor-infiltrating lymphocytes (TIL) from 44 metastatic melanoma patients using known T-cell differentiation markers. We also compared CD8⁺ TIL against the T cells from matched melanoma patients’ peripheral blood. We discovered a novel subset of CD8⁺ TIL co-expressing early-differentiation markers, CD27, CD28, and a late/senescent CTL differentiation marker, CD57. This CD8⁺CD57⁺ TIL expressed a cytolytic enzyme, granzyme B (GB), yet did not express another cytolytic pore-forming molecule, perforin (Perf). In …

The Relationship Between Vitamin D Status Of Adult Women And Diet, Sun Exposure, Skin Reflectance, Body Composition, And Insulin Sensitivity, Marisa M. Mcadler

Master's Theses

As the prevalence of vitamin D deficiency continues to grow, mounting evidence supporting its link with chronic disease strengthens suggesting vitamin D’s candidacy in the prevention and treatment of multiple disease states and their complications. Dietary guidelines, however, do not take sun exposure into account. The present study sought to explore the impact of sun exposure on vitamin D status (serum 25(OH)D), and identify other significant determinants of serum levels which may have the greatest effects on overall health. Participants (n = 34) were pre-menopausal women aged 18 to 50 years (mean age 39 ± 6 years), who had their …

Targeted Sirna Delivery Methods For Rnai-Based Therapies, Di Chen

Electronic Thesis and Dissertation Repository

RNAi has great potential in future therapeutics as it has the ability to regulating many disease-related genes. However, many barriers prevent practical applications. To overcome the barriers, the specific targeting, efficient delivery system, the validated gene and the potent siRNA sequence are all vital important. The studies throughout this thesis have been focued on examining the validation of three RNAi therapies for two different disease models: allergic contact dermatitis and melanoma. For allergic contact dermatitis, I developed and tested a novel topical delivery system for siRNAs targeting TNFα (siTNFα) and MyD88 siRNA (siMyD88). While siRNAs applied without the transdermal enhancer …

What Is The Effectiveness Of Onabotulinumtoxina (Botox®) In Reducing The Number Of Chronic Migraines (Cm) In Patients 18-65 Years Old?, Kristin A. Beddingfield

PCOM Physician Assistant Studies Student Scholarship

OBJECTIVE: The objective of this selective EBM review is to determine whether or not onabotulinumtoxinA (Botox®) is effective in reducing the number of chronic migraines (CM) in patients 18-65 years old? Study Design: Review of three published, double blind randomized controlled trials were used for this review, which were found on PubMed; were selected based on their relevance to the clinical question and if they included patient oriented outcomes.

OUTCOMES MEASURED: The outcomes measured were headache/migraine free days measured by >50% responder rate analysis, the Treatment Responder Rate based on Physician Global Assessment, and total adverse events reported by …

Is Modafinil (Provigil®) Effective In Improving Cognitive Function In Adults With Narcolepsy?, Stephanie V. Bui

PCOM Physician Assistant Studies Student Scholarship

OBJECTIVE: The objective of this selective EBM review is to determine whether or not modafinil (Provigil®) is effective in improving cognitive function in adults with narcolepsy.

STUDY DESIGN: Review of all English language primary randomized controlled trials from 1996 to 2010.

DATA SOURCES: Double-blind, randomized controlled trials that compared modafinil (Provigil®) to a visually matched placebo were found using OVID, MEDLINE, and Cochrane Databases.

OUTCOME(S) MEASURED: Each of the three trials assessed the effect of modafinil on cognitive and executive function by Low-Resolution Brain Electromagnetic Tomography (LORETA), and the following assessment tools: Epworth Sleepiness Scale (ESS), Multiple Sleep …

Is Yoga An Effective Management Strategy For Disordered Eating?, Patricia G. Byrne

PCOM Physician Assistant Studies Student Scholarship

OBJECTIVE: The objective of this selective EBM review is to determine whether yoga is an effective management strategy for disordered eating.

STUDY DESIGN: Review of three English language primary studies published in 2007, 2009, and 2010.

DATA SOURCES: Three randomized control trials that evaluated yoga as a treatment intervention for disordered eating found using Medline@OVID and PubMed.

OUTCOME MEASURED: Outcomes were interpreted by eating disorder severity as measured on the Eating Disorder Examination, Eating Disorder Diagnostic Scale, and Binge Eating Scale. Secondarily, there was an assessment of associated attitudes and behaviors towards eating, including body satisfaction, physical activity level, …

Generation And Characterization Of Peptide Fusion Proteins, Brianna L. Probasco

Graduate School of Biomedical Sciences Theses and Dissertations

Pathogenic Th17 cells drive progression of many autoimmune diseases. Th17 cells develop from naïve T cells in the immune system after antigen-driven stimulation in a specific cytokine environment. Normally, T cells act to fight off infection, but when not properly controlled, they can cause disease. The cytokine interleukin-23 (IL-23) plays an essential role in the expansion of pathogenic Th17 cells. IL-23 is a heterodimeric protein, composed of a p19 alpha chain and a p40 beta chain. The p40 is also part of IL-12 and binds to the IL-12 receptor beta 1 (IL-12Rβ1) subunit. Thus, it follows that the IL-23 receptor …