541 research outputs found

    HDAC6 INHIBITION REVERSES LONG-TERM DOXORUBICIN-INDUCED COGNITIVE DYSFUNCTION BY RESTORING MICROGLIA HOMEOSTASIS

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    One in 8 women in the US will be diagnosed with breast cancer. Currently, doxorubicin is one of the most effective chemotherapies for breast cancer. Unfortunately, up to 60% of survivors report long-term chemotherapy-induced cognitive dysfunction (CICD) characterized by deficits in working memory, processing speed, and executive functioning. Currently, no interventions for CICD have been approved by the US Food and Drug Administration. I show here that a 14-day treatment with a blood-brain barrier permeable histone deacetylase 6 (HDAC6) inhibitor successfully reverses long-term CICD following a therapeutic doxorubicin dosing schedule in female mice, as assessed by the puzzle box test and novel object/place recognition test. Long-term CICD was associated with a decreased expression of the postsynaptic protein PSD95, but no decrease in the presynaptic protein synaptophysin, in the hippocampus. I did not detect a significant decrease in mitochondrial function or morphology in brain synaptosomes, myelination in the cingulate cortex using Black Gold II staining, or changes in astrocyte reactivity as assessed by anti-GFAP immunofluorescence staining. Using advanced imaging techniques and single-nucleus RNA sequencing, I demonstrate that doxorubicin-induced changes are associated with decreased microglial ramification and alterations in the microglia transcriptome that suggest a neurodegenerative microglia phenotype closely resembling stage 1 disease-associated microglia (DAMs). HDAC6 inhibition completely reversed these doxorubicin-induced alterations, indicating a restoration of microglial homeostasis. These results suggest that a stage 1 DAM-like microglia phenotype and decreased postsynaptic integrity contribute to long-term CICD. Moreover, HDAC6 inhibition shows promise as an efficacious pharmaceutical intervention to alleviate CICD and improve quality of life of breast cancer survivors

    TRAUMA-INFORMED CASE MANAGEMENT PRACTICE FOR YOUTH EXPERIENCING HOMELESSNESS: CONNECTION, HEALING AND TRANSFORMATION

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    Young people experiencing homelessness in the United States are some of the most resilient individuals in our society. They, like all young people, are filled with extraordinary potential. However, the multiple and chronic trauma that these young people experience, caused by systemic injustices such as poverty, violence and oppression, both before and while experiencing homelessness, deeply violate their dignity and human rights. For youth experiencing homelessness, their very survival physically, mentally, emotionally, spiritually and economically is threatened daily. Experiences such as: abuse, neglect, poverty, housing instability, loss, family and community violence, victimization, exploitation, hunger, illness, criminalization, social isolation, rejection and marginalization profoundly influence a young person’s sense of safety and ultimately their health and wellbeing. The purpose of this project is to create a response to youth homelessness that restores and enhances dignity and provides opportunities for connection, healing and transformation. This will be accomplished by the creation of a Trauma-Informed Case Management Toolkit for case managers working with youth experiencing homelessness. In short, this response addresses the individual needs of young people experiencing homelessness while also encouraging social change. The trauma-informed case management toolkit, a holistic guide in delivering case management services, connects theory to practice for case managers, infusing principles of trauma-informed care, attachment theory, youth development and social justice into case management practice with youth experiencing homelessness. The intention is that the trauma-informed case management toolkit can be used as part of the larger response in addressing youth homelessness from an individual, community, societal, and policy perspective

    Prevalence Of Asymptomatic Chlamydia In Pregnancy

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    Chlamydia has become the most prevalent sexually transmitted disease in the United States. Most infected women are asymptomatic carriers of the infection. Chlamydia is not a reportable disease in the State of Mississippi. Therefore, no data are available regarding the magnitude of infection in Northeast Mississippi. The purpose of this study was to identify asymptomatic chlamydial infections in pregnant women attending a midwifery clinic in Northeast Mississippi. The Neuman Systems Model identifying levels of prevention was utilized as the theoretical framework. The research questions guiding the study were what percentage of pregnant women are asymptomatic and what are the clinical, behavioral, and demographic characteristics of these women? A descriptive correlational study was conducted at a midwifery clinic in Northeast Mississippi from March 1992 to September 1992. Subjects were 97 pregnant women. Chart review was utilized to identify clients with positive tests for chlamydia. The McAlpin Record of Demographic and Clinical Characteristics of Chlamydial Infection was utilized to identify demographic, behavioral, and clinical characteristics. Descriptive statistics were used to describe the sample. The chi-square (%^) value of 48.984, iv df = 4, 2 = 0.000 revealed that the presence or absence of clinical characteristics were not predictive of test results. Correlational statistics, Pearson r = 0.1178, p = 0.1571 revealed no correlation between tests results and clinical characteristics

    Rehabilitation of Highway Pavements - an Engineering Challenge

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    Numerical Modeling of Mobile Bay

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    A numerical model was developed for the Mobile Bay system to investigate the impacts associated with certain system alterations. The Adaptive Hydraulics (AdH) Code was used to validate the numerical model for hydrodynamics and transport. Due to the physics based nature of the AdH numerical model, the validated model could be altered to represent the plan conditions (removal of the Mobile Bay Causeway). Comparisons of the base and plan model results indicate the impacts of removing the causeway are not widespread and are primarily limited to Chocolatta Bay and the areas adjacent to the causeway. The model results suggest an increased exchange of water between Chocolatta Bay (north of the causeway) and Mobile Bay for the removed causeway configuration. Chocolatta Bay also experiences an increased inflow from the river systems which result in increased suspended sediment concentrations and sediment deposition

    Bridging the Gap--Theory and Current Practice

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    Costume Design for Qui Nguyen’s She Kills Monsters

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    The following thesis details the process of creating costume designs and implementing them in the production of She Kills Monsters which was produced at the University of Arkansas Black Box Theatre in the Fall of 2018. Throughout this thesis I will explain how the costumes went from initial research and conversations with the director to the final products on the stage. The account of this includes an analysis of the script, collages of photos used for inspiration, portrait gallery, research, rough sketches, renderings with fabric swatches, production photos, and my evaluation of the process as a whole

    Funding: Issues and Options

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