Lung cancer is a particularly devastating disease, accounting for the most deaths among all cancer types in the United States. Despite a reduction in the country’s smoking rates, cigarette smoking remains the number one risk factor for lung cancer. Additionally arsenic exposure, which occurs primarily through contaminated drinking water in the U.S., is associated with increased lung cancer incidence. The nucleotide excision repair (NER) pathway is critical for maintenance of genomic fidelity, removing DNA lesions that could otherwise promote DNA mutations and drive carcinogenesis. Tobacco smoking introduces significant amounts of DNA damage and produces characteristic DNA mutations found in lung cancers of smokers, and arsenic increases lung cancer risk in smokers beyond the risk of smoking along. The contributions of these chemicals to DNA damage and cancer have been well documented, but few studies have examined their effects on DNA repair pathways, particularly the nucleotide excision repair (NER) pathway. Arsenic, while not directly mutagenic, promotes the carcinogenicity of other compounds including agents that produce DNA damage that is repaired by the NER pathway. In this dissertation I investigated the effects of cigarette smoke condensate (CSC, a whole-smoke tobacco surrogate) and arsenic on NER. I observed that CSC or arsenic treatment inhibited NER as measured by a slot-blot assay using UV-induced photolesions as model substrates to measure NER. The abundance of Xeroderma Pigmentosum complementation group C (XPC), a critical NER protein, was significantly reduced in all lines treated with either chemical, while XPA protein was unaffected. CSC and arsenic also affected RNA levels of certain NER genes. Finally, proteasome-regulated XPC turnover was affected by CSC and arsenic treatment, suggesting a potential mechanism for XPC protein inhibition. The observed impairment of NER by CSC is critically important in tobacco cancer etiology – CSC introduces DNA damage, some of which is repaired exclusively by NER, and CSC inhibits the NER pathway as well, providing a two-sided assault on cellular genetic fidelity. I then adapted the NER assay to measure repair in lymphocytes isolated from human subjects of a study investigating the high incidence of lung cancer in Appalachian Kentucky. I observed an age-dependent decline in NER efficiency that was modulated by subject smoking status and a reduced NER efficiency among current smokers in the lung cancer patient population compared to control subjects in the youngest age group, suggesting individual DNA repair capacity measured with this repair assay may be a biomarker for lung cancer susceptibility.

Recent reports detail a rise in the practice of home food preservation in the United States due to economic woes, nutritional concerns, and increasing devotion to local food production.Home food preservation is the processing of foods in order to extend its shelf-life. Current common approaches to preserving foods at home include pressure canning, freezing, drying, water bath canning, and cellaring/storing. Local food production in four Kentucky counties were examined through in-depth qualitative interviews with home food preservation practitioners to yield a rural/urban comparison. Forty home food preservation practitioners were interviewed between Fall 2009 and Fall 2013. The primary question driving this project is what motivates those who grow gardens and practice home food preservation in an era of readily available, relatively cheap foodstuffs? Secondary questions include, how do the motivations of home food preservation practitioners compare in rural and urban areas? What are the links, if any, between home food preservation and environmental sustainability concerns in rural and urban areas? Each of these questions will be examined through a mixture of qualitative methods and a grounded theoretical approach. In-depth field interviews with 40 preservers, documentary filmmaking, and participant observation were conducted in two rural and two urban Kentucky counties. Interview transcripts were coded by themes, interpreted using hermeneutic analysis, and analyzed by grounded theory. Policy institutes could make gains from this research by building upon already existing community food practices. Agriculture extension agent could use these findings to inform their food preservation programs and improve safety recommendations.

Deterioration in voice quality following radiation therapy for the treatment of laryngeal cancers (LC) is well documented in literature. The majority of studies show that these voice problems are long term and in some cases permanent. Deterioration in voice quality, especially over a period of time could lead to significant communication difficulties in daily life or in some cases could even result in loss of profession. Despite the negative effects of radiation therapy on voice quality being well documented, few studies have focused on the efficacy of voice therapy in the irradiated LC population. The purpose of this study was to investigate the efficacy of a well researched, evidence based voice therapy approach, known as Vocal Function Exercises (VFEs) in improving vocal function in patients who have been irradiated for LCs. The present study conducted in three systematic stages with distinct and related study aims. The first involved characterizing the head and neck cancer treatment seeking population at the University of Kentucky (UK). Stage 2 involved characterizing vocal function following irradiation for LC using a multidimensional assessment approach. Stage 3 was a phase 2 clinical trial aimed at treating these deficits in vocal function identified through stage 2 using a systematic evidence based voice therapy approach, Vocal Function Exercises. For the phase 2 clinical trial, the comparison group received vocal hygiene (VH) counseling. Observations from stage 1 showed that majority of patients from the treatment seeking population at UK between a 3 year time period from 2008 to 2010 were diagnosed with laryngeal cancers and were treated with chemoradiation therapy. Stage 2 demonstrated a multidimensional deterioration in vocal function following radiation therapy for laryngeal cancers. Stage 3 demonstrated a significant improvement in vocal function across the primary outcome measure (Voice Handicap Index) as a result of VFE+VH. Improvements were also seen in select parameters across the five domains of voice assessment in the VFE group. No significant improvements were observed in the vocal hygiene group in any parameters in each domain of voice assessment. Our study demonstrated adults irradiated for laryngeal cancers demonstrated a multi-dimensional deterioration of vocal function. These changes were long term since study participants were 2- 7 years post radiation therapy. Implementation of VFE+VH demonstrated a significant improvement in voice related quality of life and select parameters across the five domains of voice assessment. The present study demonstrated promising preliminary evidence for the use of VFE+VH to improve vocal function in patients irradiated for laryngeal cancers.

Financial literacy is a national problem; many studies confirmed that Americans have low levels of financial literacy. There is little to no research about financial literacy in Appalachia, and the level of financial literacy was unknown for Appalachian Kentucky. There is a problem deserving attention which can be seen by examination of the 3 key financial indicators. Many researchers found the Appalachian Kentucky region deficient regarding poverty rates, unemployment rates, and personal income rates. The purpose of this study was to develop a baseline level of financial literacy of Appalachian Kentuckians and to compare it to national levels. Becker's theory of human capital served as the theoretical framework of this study. The research questions asked the difference between the levels of financial literacy of Appalachian Kentuckians and Americans. A survey design was used to collect data from residents in an Appalachian Kentucky county (n = 35) that was mathematically average based on the key financial indicators as reported by the Appalachian Regional Commission. The national financial literacy rate was derived from the National Financial Capability Study. A one-sample t test indicated that the financial literacy level of Appalachian Kentuckians is less than the national level. Multiple linear regression analysis indicated that financial literacy levels can be predicted either by personal income or poverty. This study offers positive social change by providing a baseline understanding of financial literacy in Appalachian Kentucky to draw more attention to the improvement needs in this area. Improving financial literacy has the potential to improve key financial indicators of the region, and thus, the lives of Appalachian Kentuckians.