Background: Alzheimer’s disease (AD) is a type of Dementia and a neurodegenerative disease that is characterized by the gradual degrading of both memory and cognitive functions. According to the World Health Organization (WHO), the prevalence of AD is increasing globally. Currently, AD is the sixth leading cause of mortality in the United States. As the ageing population increases in the United States, it is possible that AD will move up the ladder in the top cause of mortality. Although the prevalence of AD in most urban parts of developed nations such as the United States is widely known, little is known about the prevalence and early diagnosis of the disease among the rural populations. According to a study by the Centers for Disease Control and Prevention (CDC), on deaths from AD between 1999 and 2014, most mortality are concentrated in the rural counties of the Appalachian region of the United States, where the mortality rate has increased by an alarming 75%. Our study focuses on the Northeast Tennessee region, which is a prominent part of the Appalachian region. We examine the prevalence of Alzheimer’s disease in the Northeast Tennessee region compared to other parts of the state of Tennessee. We sought to understand whether there is a likely association between the disease and the rural counties in the Northeast Tennessee region. Methods: We performed a cross-sectional study that computes and compares between the Prevalence Odds Ratio (POR) of the 2013 to 2015 Centers for Medicare and Medicaid Services Public Use Files data on rural versus urban counties in the Northeast Tennessee region followed by the Northeast Tennessee counties versus other counties in Tennessee. In addition, we collected primary data from 44 experts and professionals working in AD-related fields within the Northeast Tennessee region using an online survey that captures the perceived observation of the experts and professionals about the increasing prevalence of AD over the last five years. Results: Findings show that the rural counties within the Northeast Tennessee region had 18.3% (POR: 1.183, C.I: 1.113-1.258), 4.7% (POR: 1.047, C.I: 0.982-1.117), and 19% (POR: 1.190, C.I: 1.121-1.264) increased odds of prevalence of AD compared to the urban counties within the region in 2013, 2014, and 2015, respectively. Similarly, the Northeast Tennessee region as a whole, had increased odds of 22.7% (POR: 1.227, C.I: 1.203-1.250), 22.5% (POR: 1.225, C.I: 1.202-1.249), and 21.2% (POR: 1.212, C.I: 1.189-1.235) of AD compared to all other counties in Tennessee during the same periods. Conclusions: Statistical analysis and findings from experts and professionals working with patients with AD in the Northeast Tennessee region show that there are more cases of AD in the Northeast Tennessee region compared to the last five years. We suggest early screening strategies for possible decrease in the morbidity and mortality rates in Northeast Tennessee region.

Objective:The present study examined mothers’ emotion socialization of 3-year–old children with behavior problems, to determine whether emotion socialization practices, as well as the relation between these practices and child functioning, varied across ethnicities. Method: Participants were 156 preschoolers with behavior problems. Mothers were European American (n = 98), Latina American (n = 40; predominately Puerto Rican), and African American (n = 18). Audio taped mother-child interactions were coded for emotion socialization behaviors. Results: Overall, this study provided evidence for both differences and similarities across ethnicities on parental emotion socialization practices. Ethnic differences in use of emotion socialization practices were only found for mothers’ emotion focused reactions, minimizing reactions, and non-responses to negative affect. However, ethnic differences emerged in the relations between emotion socialization practices and child functioning. Several emotion socialization parental behaviors were differentially related to current child internalizing and externalizing problems across ethnic groups. Conclusions: Results provide some support for the existence of cultural differences in emotion socialization practices and their associated child outcomes.

Efforts to improve inclusion in research have included mandating the recruitment of ethnic minorities and women into NIH funded studies. However, little research has been completed on who attends such interventions. This is particularly worrisome in populations for which attendance to interventions can have dire consequences. HIV is a public health concern for pregnant women in substance using communities, as pregnant women are much less likely to use condoms during intercourse to prevent HIV. Group modular HIV prevention interventions have long been the standard for HIV prevention. However, little attention in research on HIV prevention interventions RCTs has been focused on attendance to these interventions. This study examined predictors of intervention and control group attendance in a randomized controlled trial comparing a 5-session Safer Sex Skill Building (SSB) intervention to a 1-session HIV education control group in a sample of pregnant women at risk for prenatal substance use. This study identified psychosocial and mental health variables associated with both 1 session control group and 5-session SSB intervention attendance as well as endeavored to identify the number of sessions necessary to attend to achieve an adequate dose in treatment. Findings include younger age and marital status as being predictive of participation in the one session HE control group and having a trade, skill, or profession as being predictive of participation in the five session SSB intervention group. Further research is needed to understand what factors may impact five-session SSB group attendance.

Synthetic cathinones and related agents represent an international drug abuse problem, and at the same time an important class of clinically useful compounds. Structure-activity relationship studies are needed to elucidate molecular features underlying the pharmacology of these agents. Illicit methcathinone (i.e., MCAT), the prototype of the synthetic cathinone class, exists as a racemic mixture. Though the differences in potency and target selectivity between the positional and optical isomers of synthetic cathinones and related agents have been demonstrated to have important implications for abuse and therapeutic potential, the two MCAT isomers have never been directly compared at their molecular targets: the monoamine transporters (MATs). Additionally, previous studies have found that the carbonyl oxygen atom can be replaced with a methoxy group, but this results in two chiral centers (i.e., four possible optical isomers for synthesis and evaluation). Here, the individual isomers of MCAT, their racemate, and achiral MCAT analogs were prepared where necessary, and examined in vitro and in silico at the MATs. All agents were active as substrates, with a rank order of potency suggesting that α-position chirality, in either configuration, is favored but not required, with the S(-) configuration slightly preferred. Either chiral center removal approach resulted in a reduction in potency, suggesting both favorable interactions with the α-methyl, and limited bulk tolerance. To further investigate this possibility, docking studies were conducted using homology models of the MATs. Common binding modes were identified that were similar to the binding mode of S(+)amphetamine co-crystallized at drosophila DAT. Taken together, these studies supported our conclusions, as steric hindrance was observed in the α-methyl region of the proposed binding site for the R(+)MCAT isomer. Inclusion of the original synthetic cathinones among Schedule I controlled substances has driven the clandestine development of a second generation of agents, resulting in an array of new synthetic cathinones diverse in structure and effect.Pyrrolidinophenones are a major constituent of second-generation bath salts. Little is known about their structure-activity relationships. Here, we have synthesized and examined a series of aryl-substituted pyrrolidinophenone analogs, as well as an achiral pyrrolidinophenone analog, utilizing novel synthetic chemistry and an innovative cell-based epifluorescence Ca2+ imaging technique. Herein, we evaluated the neurochemical properties of these novel compounds at the dopamine transporter (DAT), considered to exert a major role in actions of drugs of abuse. For future structure-activity relationship studies, additional analogs of synthetic cathinone-related agents were produced using novel synthetic approaches, including analogs and isomers of known amphetamine drugs of abuse. Finally, though much has been learned about the role of the dopamine and serotonin transporters in the mechanisms of action of synthetic cathinones, the role of the norepinephrine transporter is poorly understood. Homology models of the human norephinephrine transporter were built and docking studies conducted to inform the study of MAT ligand selectivity, activity, and binding. In conclusion, these studies represent progress towards the establishment of comprehensive structure-activity relationships for synthetic cathinones and related agents. Particular emphasis was placed on the SAR of the phenylalkylamine α-carbon in the synthetic cathinone context, and the role of the norepinephrine transporter in their activity.

This work asks how and for whom humiliation can be therapeutic. J. M. Coetzee, in his works Waiting for the Barbarians, Life & Times of Michael K and Disgrace, does not simply critique the mentality of Empire, an “Enlightenment” or colonialist mode of knowing that knows no bounds to reason, but offers an alternative through the Magistrate, Michael K and David Lurie, all of whom are brutally shamed and “abjected”. Each character, I propose, experiences a Lacanian “therapy of humiliation” resulting in a subversion of their egos, which they come to understand as antagonistic, a site of misrecognition. In doing so, these characters confront limitation, whether by means of a Lacanian “death drive” or the abjection of the self. I argue, this subversion of their egos necessitates a return to the humility of the body resulting in a new ethical openness to others and an engagement with the world through “care” or “love” or “beauty” which manifests as careful negotiation and attentiveness. Confrontation with death, thus, allows the Magistrate, Michael K and David Lurie to slough off “Enlightenment” values in favor of an anti-humanist way of living.

The purpose of the present study was to examine general loneliness, hospital loneliness, and the patient-physician relationship in regards to their associations with Bone Marrow Transplant (BMT) recovery outcome variables (days until engraftment and quality of life). Fifteen (66.7% female, 33.3% male; 93.3% white, 6.7% Black/African American; average age 61.73) individuals who had an allogeneic or autologous BMT at The Mayo Clinic of Jacksonville completed the FACT-BMT, UCLA-Loneliness Scale Version 3, the CARE Measure, and provided disease and treatment information at the 6 month posttransplant date (+/- 30 days). Patients recovering from BMT indicated significantly higher scores of hospital loneliness in comparison to their general loneliness scores. This increase is believed to represent the outcome of experiencing hospital isolation during the post-transplant recovery process. Increases in hospital loneliness were marginally significant in predicting decreases in the patients overall quality of life. The patient physician consultational relationship was found to have a significant relationship with the number of days until engraftment, however the direction of the relationship was opposite the hypothesized direction. This may suggest that engraftment influences the quality of the relationship instead of vice versa. These results imply that there is a relationship between hospital isolation and increases in the amount of loneliness experienced during recovery from a BMT. Loneliness has been found to have a negative relationship with a number of physiological and quality of life outcomes. The present study also elucidates possible correlates with the patient-physician relationship.

Objective: To determine the feasibility of an online cognitive behavioral therapy for insomnia (CBT-I) in bereaved older adults. Participants: The study participants include adults aged 55 and older (N = 30) that lost a loved one within the past five years and are currently experiencing symptoms of insomnia. Methods: This study used an experimental design and was guided by the Transitions Theory developed by Meleis. Descriptive statistics and t-tests were used to measure changes within and between groups. Experimental arm had the CBT-I online treatment and the control arm had attention controlled online tasks. Intervention fidelity was measured. Results: The online CBT-I intervention is a feasible intervention for bereaved older adults with insomnia. High retention rates were shown in both groups, and both groups’ insomnia and mood symptoms improved at post- study measurement. There were no statistically significant differences seen in any measure between groups. Conclusions: Transitions in older adult life includes loss of friends and family as well as development of sleep issues. The Transitions Theory is useful for informing the design of behavioral interventions in this older population. Further research is needed to understand how sleep can be improved by cost effective online interventions that might not include solely CBT-I.

The purpose of the present study was to investigate the influence of pain causal attributions on patient pain-related functioning, treatment engagement, and clinical outcomes. Additionally, the impact of discordant pain causal attributions between patients and their providers as well as between interdisciplinary providers was examined. Patients rated their pain functioning and causal pain attributions during a regular clinic visit. Following the patient’s visit both the behavioral medicine provider and internal medicine resident provided ratings of similar pain-related functioning domains and causal attributions. Follow-up data were collected from the electronic medical record three months following that clinic visit. Overall, results revealed that patients’ chronic pain attributions did influence pain-related functioning, however the impact was relatively small. There was insufficient evidence to conclude that chronic pain attributions influence a patient’s readiness to adopt self-management coping strategies and their subsequent treatment engagement. Additionally, results confirmed that different health care disciplines attribute the cause of patients’ chronic pain in distinct ways and these unique perspectives can lead to discrepant pain-related functioning assessments between providers. Discordant ratings between providers were shown to influence referring patterns for interdisciplinary services and the patient’s overall opioid dose. Similarly, discrepancies between patients and their providers influenced subsequent referral for behavioral health services, the patient’s attendance at those visits, and their overall morphine equivalent doses. Together the results indicate the important role pain attributions can play in chronic pain management and highlight the central role of the patient-provider and provider-provider relationship.

Adolescence and young adulthood are the periods of development associated with the highest amount of risk-taking. One theory, the Dual-Systems model, suggests that this could be due to an imbalance in the maturation of two brain systems: reward appraisal, which matures first, and cognitive control, which matures later. This imbalance may be the cause of adolescents’ tendency to favor immediate rewards, disregarding consequences. Depressed adolescents, however, behave differently. While it is not exactly clear whether they take more risks or fewer risks, depressed adolescents display different interactions and decision making with their peers than non-depressed adolescents. This study attempted to use these patterns of behavior already identified in previous research to predict where an adolescent would fall on a depression continuum based on their Self-Focused and Other-Focused risk behaviors. Results did not find a link between depression and either type of risk. Results may be inconclusive due to issues within the data and data collection process.

<p>This thesis presents research investigating structural neural correlates of major depressive disorder (MDD). Although there are clear clinical differences between early- and late-onset MDD, they are still subject to the same diagnostic criteria and treatment strategy. Whether these differences translate into differences in cortical structure was examined in this study. By directly comparing early-onset (EOD) and late-onset (LOD) patients, we test whether age-of-onset results in changes in the extent or spatial pattern of cortical thinning.</p> <p>Chapter 1 provides a general background on the cerebral cortex, followed with a focus on cortical thickness. Chapter 2 presents a comprehensive review of the clinical and neurobiological literature on major depressive disorder as it pertains to age-of-onset. Three working hypotheses regarding the differences between early- and late-onset depression are presented and discussed.</p> <p>The results presented in this thesis show that there are both differences and similarities in cortical thickness between patients with EOD and LOD, with differences reflecting spatial extent, region-specificity, and magnitude of thickness differences. We confirmed the hypothesis of greater thinning in the dorsal lateral prefrontal cortex in depressed patients compared to healthy controls. We also correlated cortical thickness with clinical variables, which resulted in the finding of a positive correlation in the posterior cingulate cortex with illness severity.</p> <p>Few studies have used age-of-onset as a factor, which may account for some of the heterogeneity and inconsistent results seen in studies of MDD. We found that depression onset in early life is associated with greater disturbances in cortical thickness than LOD, possibly reflecting atypical development. These results provide novel insights into vulnerability and how development of depression is differentially affected by age.</p> / Master of Science (MSc)