Objective: To determine if patients’ insurance status or the income level of their zip code of residence affect their quality of life or overall survival after enrollment in clinical trials for cancer treatment. Methods: Data were collected from cancer treatment trials conducted through the North Central Cancer Treatment Group and the Alliance for Clinical Trials in Oncology. 700 subjects with baseline quality of life scores were analyzed to explore potential differences in quality of life indicators by insurance group. 624 patients with valid US zip codes were also analyzed based on the median household income of their zip code to determine any associations with quality of life. Overall survival was also analyzed by insurance group and by income quartile. Results: 700 subjects (mean age 59 years, 53% male) were included. 49% had private insurance only, 30% had public insurance only, 8.9% had both private and public insurance, 1.4% had no insurance, and 10% had other insurance. 13% of patients came from zip codes in the bottom quartile by median income, 20% came from the second quartile, 25% from the third quartile and 42% from the top quartile. No significant differences were found in baseline quality of life scores between insurance groups or income quartiles. Patients with both private and public insurance had higher baseline fatigue scores compared to only private, only public, or other insurance. No significant difference was found in baseline fatigue scores by income quartile. No significant differences were found in overall survival by insurance group or income quartile. Conclusions: Patients with both private and public insurance may need more extensive interventions than patients with other insurance statuses due to their higher baseline fatigue scores. Future studies are needed to further investigate the effects of neighborhood advantage level on quality of life indicators.

The purpose of this study was to find an appropriate solution in reducing inflammation around the ankle joint for Rheumatoid Arthritis (RA) patients, so they are able to increase their endurance and improve their overall quality of life. RA patients have to deal with a significant amount of complications that include chronic inflammation, continuous pain in their joints, and overwhelming stress. In addition, it is very common for RA patients to develop severe mental issues that only makes matters worse. As a result, it is imperative that treatments are provided to RA patients to improve their current situation. Three devices from the current market, made for reducing inflammation of the ankle, were chosen for evaluating the effectiveness of each device. It was determined that with 95% confidence that the Gonicc Professional Foot Sleeve was the most effective in reducing inflammation. A prototype was developed based on the feedback of the participants. Further improvements, the prototype will be compared against the Gonicc Professional Foot Sleeve to determine which is the best solution to improve millions of RA patients' lives.

Annually approximately 1.5 million Americans suffer from a traumatic brain injury (TBI) increasing the risk of developing a further neurological complication later in life [1-3]. The molecular drivers of the subsequent ensuing pathologies after the initial injury event are vast and include signaling processes that may contribute to neurodegenerative diseases such as Alzheimer’s Disease (AD). One such molecular signaling pathway that may link TBI to AD is necroptosis. Necroptosis is an atypical mode of cell death compared with traditional apoptosis, both of which have been demonstrated to be present post-TBI [4-6]. Necroptosis is initiated by tissue necrosis factor (TNF) signaling through the RIPK1/RIPK3/MLKL pathway, leading to cell failure and subsequent death. Prior studies in rodent TBI models report necroptotic activity acutely after injury, within 48 hours. Here, the study objective was to recapitulate prior data and characterize MLKL and RIPK1 cortical expression post-TBI with our lab’s controlled cortical impact mouse model. Using standard immunohistochemistry approaches, it was determined that the tissue sections acquired by prior lab members were of poor quality to conduct robust MLKL and RIPK1 immunostaining assessment. Therefore, the thesis focused on presenting the staining method completed. The discussion also expanded on expected results from these studies regarding the spatial distribution necroptotic signaling in this TBI model.

Patients need to know current and available options for prosthetic devices. Devices are categorized depending on the region of amputation and their purpose. Retrospection on the history of prosthetic devices leading into modern ones allows for an interpretation of successes and necessary improvements moving forward. One promising avenue for prostheses is the development of neuroprostheses that much more closely resemble some of the functionality taken for granted in natural limbs. Proprioception, more commonly known as the ‘sixth sense’, would be a very desirable characteristic of these devices and is the subject of current research efforts. In the meantime, it is necessary to help patients evaluate what products are out there that identify more strongly with their individualized preferences.

My honors thesis focuses on the technological aspects and the legal impacts of prosthetics and advanced prosthetics. There is a lot of case law dealing with early prosthetics when it comes to worker’s compensation, airport security, prisons and sports. However, there has been little case law that has dealt with advanced prosthetics. As prosthetic limbs become more technologically advanced and intertwined with one’s identity, it is crucial that laws are made to draw a new line between person and property. The innovation of prosthetic limbs has just begun and will surely face setbacks along the way, but the benefits will be worth it once the law catches up with the rapidly advancing technology.

Traumatic brain injury (TBI) is defined as an injury to the head that disrupts normal brain function. TBI has been described as a disease process that can lead to an increased risk for developing chronic neurodegenerative diseases, like frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis (ALS). A pathological hallmark of FTLD and a hallmark of ALS is the nuclear mislocalization of TAR DNA Binding Protein 43 (TDP-43). This project aims to explore neurodegenerative effects of TBI on cortical lesion area using immunohistochemical markers of TDP-43 proteinopathies. We analyzed the total percent of NEUN positive cells displaying TDP-43 nuclear mislocalization. We found that the percent of NEUN positive cells displaying TDP-43 nuclear mislocalization was significantly higher in cortical tissue following TBI when compared to the age-matched control brains. The cortical lesion area was analyzed for each injured brain sample, with respect to days post-injury (DPI), and it was found that there were no statistically significant differences between cortical lesion areas across time points. The percent of NEUN positive cells displaying TDP-43 nuclear mislocalization was analyzed for each cortical tissue sample, with respect to cortical lesion area, and it was found that there were no statistically significant differences between the percent of NEUN positive cells displaying TDP-43 nuclear mislocalization, with respect to cortical lesion area. In conclusion, we found no correlation between the percent of cortical NEUN positive cells displaying TDP-43 nuclear mislocalization with respect to the size of the cortical lesion area.

Cancer treatments such as chemotherapy and radiation are expensive, painful, and often ineffective, as they compromise the patient’s immune system. Genetically-modified Salmonella Typhimurium (GMS) strains, however, have been proven to target tumors and suppress tumor growth. The GMS then undergo programmed lysis, optimally leaving no trace of Salmonella in the body. Additionally, constant culturing of S. Typhimurium changes the pH of the culture medium. The objective of this research is to investigate using Salmonella to induce changes in the typically acidic tumor microenvironment (TME) pH, ideally hindering tumor growth. Future studies involve utilizing Salmonella to treat a multitude of cancers.

Alginate microspheres have recently become increasingly popular in the realm of drug delivery for their biocompatibility, nontoxicity, inexpensiveness, among other factors. Recent strict regulations on microsphere size have drastically increased manufacturing cost and waste, even though the effect of size variance on drug delivery and subsequent performance is unclear. If sphere size variance does not significantly affect drug release profiles, it is possible that future ordinances may loosen tolerances in manufacturing to limit waste produced and expenditures. We use a mathematical model developed by Nickel et al. [12], to theoretically predict drug delivery profiles based on sphere size, and correlate the expected release with experimental data. This model considers diffusion as the key component for drug delivery, which is defined by Fick’s Laws of Diffusion. Alginate, chosen for its simple fabrication method and biocompatibility, was formed into microspheres with a modified extrusion technique and characterized by size. Size variance was introduced in batches and delivery patterns were compared to control groups of identical size. Release patterns for brilliant blue dye, the mock drug chosen, were examined for both groups via UV spectrometry. The absorbance values were then converted to concentration value using a calibration curve done prior to experimentation. The concentration values were then converted to mass values. These values then produced curves representing the mass of the drug released over time. Although the control and experimental values were statistically significantly different, the curves were rather similar to each other. However, when compared to the predicted release pattern, the curves were not the same. Unexpected degradation caused this dissimilarity between the curves. The predictive model was then adjusted to account for degradation by changing the diffusion coefficient in the code to a reciprocal first order exponent. The similarity between the control and experimental curves can insinuate the notion that size tolerances for microsphere production can be somewhat lenient, as a batch containing fifteen beads of the same size and one with three different sizes yields similar release patterns.

Alginate microspheres have recently become increasingly popular in the realm of drug delivery for their biocompatibility, nontoxicity, inexpensiveness, among other factors. Recent strict regulations on microsphere size have drastically increased manufacturing cost and waste, even though the effect of size variance on drug delivery and subsequent performance is unclear. If sphere size variance does not significantly affect drug release profiles, it is possible that future ordinances may loosen tolerances in manufacturing to limit waste produced and expenditures. We use a mathematical model developed by Nickel et al. [12], to theoretically predict drug delivery profiles based on sphere size, and correlate the expected release with experimental data. This model considers diffusion as the key component for drug delivery, which is defined by Fick’s Laws of Diffusion. Alginate, chosen for its simple fabrication method and biocompatibility, was formed into microspheres with a modified extrusion technique and characterized by size. Size variance was introduced in batches and delivery patterns were compared to control groups of identical size. Release patterns for brilliant blue dye, the mock drug chosen, were examined for both groups via UV spectrometry. The absorbance values were then converted to concentration value using a calibration curve done prior to experimentation. The concentration values were then converted to mass values. These values then produced curves representing the mass of the drug released over time. Although the control and experimental values were statistically significantly different, the curves were rather similar to each other. However, when compared to the predicted release pattern, the curves were not the same. Unexpected degradation caused this dissimilarity between the curves. The predictive model was then adjusted to account for degradation by changing the diffusion coefficient in the code to a reciprocal first order exponent. The similarity between the control and experimental curves can insinuate the notion that size tolerances for microsphere production can be somewhat lenient, as a batch containing fifteen beads of the same size and one with three different sizes yields similar release patterns.

Evolution has driven organisms to develop a wide range of biological mechanisms to protect against cancer. Some organisms, including the sponge Tethya wilhelma and the Placozoa Trichoplax adhaerens have developed particularly effective mechanisms to suppress cancer and repair DNA damage. While these mechanisms are rooted in DNA damage repair and prevention, evidence of bacteria may suggest that endosymbionts living within the organisms may plays a role as well. Likewise, other organisms, such as the flatworm Macrostomum lignano, are proven model organisms whose extensive documentation enables more in-depth analysis of biological mechanisms associated with cancer. Sponges, flatworms, and Placozoa were exposed to X-ray radiation totaling 600 Gy, 25 Gy, and up to 240 Gy, respectively. RNA sequencing and bioinformatics analyses were undergone to determine the differential gene expression of the animals at different time points. No common response to the X-ray radiation was discovered amongst all organisms. Instead, sponges showed evidence of tumor suppression and DNA repair gene upregulation including CUBN, bacterial endosymbionts showed evidence of lateral gene transfer and different DNA repair genes including FH, and flatworms showed evidence of allelic and mutational shifts in which tumorous populations became more reliant on alternate alleles and a single variant signature. This study highlights the varying mechanisms that have evolved in different organisms and the importance of studying these novel model organisms further.