Alcoholism is a complex disease that exists as a specific set of behaviors, such as the preoccupation with obtaining alcohol and compulsive alcohol drinking. Currently, more than 18 million adults in the United States suffer from alcohol abuse or alcoholism. This disease poses serious medical and economic consequences for society. Identifying the neurobiological mechanisms that underlie alcohol drinking, specifically the transition from initiation to binge drinking is critical for improved treatments for alcoholics and the vulnerability for relapse in those recovering. Many studies have identified brain regions and molecular mechanisms that underlie various stages of alcohol abuse; however few have investigated the role of specific cell types within these areas. The overarching hypothesis of the studies in this dissertation is that cholinergic interneurons of the nucleus accumbens (NAc) are key neural substrates that underlie alcohol drinking, and as drinking continues; neuroadaptations within these cells then facilitate such behaviors as compulsive alcohol drinking. More specifically, these studies tested whether 1) cholinergic cell ablation in the NAc causes a decrease in alcohol drinking in C57BL/6J mice, 2) neuroadaptive changes in dopamine (DA) D2 receptor and cyclin dependent kinase 5 (Cdk5) occur within these cells following initiation alcohol drinking, and to a greater extent following binge alcohol drinking in C57BL/6J mice, and 3) neuroadaptive changes in DA D2 receptor and Cdk5 also occur in brain regions that have been implicated in the rewarding and reinforcing effects of alcohol in inbred alcohol-preferring (iP) rats. The present findings report a causal role for accumbal cholinergic neurons in binge alcohol drinking and identify DA D2 receptor and Cdk5 neuroadaptations following initiation and binge alcohol drinking. These studies identify the involvement of cholinergic interneurons in binge drinking and reveal alcohol-induced region- and cell-specific receptor and molecular changes that occur with continued drinking. These findings contribute to the understanding of the neurobiological mechanisms that underlie alcohol drinking, and provide the basis for cholinergic targeted treatments designed to attenuate binge drinking. These data also provide the groundwork for future studies aimed to examine receptor and intracellular molecular changes that occur with compulsive alcohol drinking, craving, and relapse.

Current treatment options for malignant brain tumors not only frequently fail to cure the disease due to local recurrence, but also may severely compromise quality of remaining life even when tumor mass is reduced in large part because they interfere with mechanisms of neuroplasticity and function of bystander tissue. The aims of this dissertation are to: (a) assess neurological impairments associated with rapid focal cortical tissue displacement; (b) evaluate the specific impact of conventional and novel treatments on neurorestoration while controlling tissue compression without the confound of related events linked to tumor physiology; (c) identify the behavioral change pattern during brain tumor progression and investigate the stealth nature of brain tumors; (d) demonstrate how anti-cancer treatments affect brain function especially when administered in the silent stages of brain tumors; and (e) develop treatment strategies that might improve therapeutic effectiveness and brain function. We adopted a new focal mass compression model providing rapid displacement of tissue in the underlying sensorimotor cortex, as well as the traditional rat and mouse glioma xenograft models that exhibit prominent tumor growth and invasion, given the varied aims and contexts of our different studies. Various conventional and novel brain tumor treatments were employed in this dissertation, including local and systemic chemotherapy, antiangiogenic agents, photodynamic therapy, and a glutamate antagonist. A neurorestorative therapy with atorvastatin was evaluated in its effects on functional recovery after photodynamic therapy. Functional outcomes were measured with an array of behavioral tests, which are sensitive to mild focal insults to the sensorimotor cortex and can detect recovery of function. Histopathological assessments consisted of Nissl staining, hematoxylin-andeosin (H&E) staining, and immunohistochemistry, depending on varied purposes, used in conjunction with a computer imaging analysis system. In clinical trials, functional outcome is as critical to gauging the success of a treatment as is patient survival time. Both preclinical screening of anti-cancer interventions for the ability to shrink tumors effectively with minimal disturbance of neuroplasticity and developing combination therapy with neurorestorative regimens following neurotoxic cancer treatments should allow for optimal promotion of plastic mechanisms in the remaining normal brain tissue.

Abstract Full-fat soyabeans (FFSB) intended for use in monogastric nutrition need to undergo heat treatment so that present anti-nutritional factors can be inactivated. Under- or over-treatment will decrease the level of amino acids available to the animal. In this study, the slope-ratio technique was used in two trials with broilers for determining the optimum treatment temperature for soyabeans. Average daily weight gain (ADWG) and feed conversion efficiency (FCE) were used as response parameters. The optimum temperature for dry extrusion of FFSB was 144 °C for Trial 1 and 138 °C for Trial 2. Similar temperature values were generated by both ADWG and FCE. Either one can therefore be used as response parameter for determining the optimal heat treatment conditions of FFSB for use in poultry feeding.

This report was developed to 1) examine current evidence-based research for cluttering therapy and 2) consider additional research outside of the field that may be of benefit for cluttering clients. It defines the disorder and briefly discusses its key characteristics. Treatment considerations reviewed include: slowed rate, heightened monitoring, using clear speech, using organized language, interacting with listeners, speaking naturally, and reducing excessive disfluencies. The typical approaches that have been used with clutterers as well as approaches that have been used with other disordered populations that address the key treatment considerations are discussed. / text

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published_or_final_version / Dentistry / Master / Master of Orthodontics

published_or_final_version / Medical Sciences / Master / Master of Medical Sciences

published_or_final_version / Medical Sciences / Master / Master of Medical Sciences