194 research outputs found

    Impaired Ethanol-Induced Sensitization and Decreased Cannabinoid Receptor-1 in a Model of Posttraumatic Stress Disorder

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    Background and Purpose Impaired striatal neuroplasticity may underlie increased alcoholism documented in those with posttraumatic stress disorder (PTSD). Cannabinoid receptor-1 (CB1) is sensitive to the effects of ethanol (EtOH) and traumatic stress, and is a critical regulator of striatal plasticity. To investigate CB1 involvement in the PTSD-alcohol interaction, this study measured the effects of traumatic stress using a model of PTSD, mouse single-prolonged stress (mSPS), on EtOH-induced locomotor sensitization and striatal CB1 levels. Methods Mice were exposed to mSPS, which includes: 2-h restraint, 10-min group forced swim, 15-min exposure to rat bedding odor, and diethyl ether exposure until unconsciousness or control conditions. Seven days following mSPS exposure, the locomotor sensitizing effects of EtOH were assessed. CB1, post-synaptic density-95 (PSD95), and dopamine-2 receptor (D2) protein levels were then quantified in the dorsal striatum using standard immunoblotting techniques. Results Mice exposed to mSPS-EtOH demonstrated impaired EtOH-induced locomotor sensitization compared to Control-EtOH mice, which was accompanied by reduced striatal CB1 levels. EtOH increased striatal PSD95 in control and mSPS-exposed mice. Additionally, mSPS-Saline exposure increased striatal PSD95 and decreased D2 protein expression, with mSPS-EtOH exposure alleviating these changes. Conclusions These data indicate that the mSPS model of PTSD blunts the behavioral sensitizing effects of EtOH, a response that suggests impaired striatal neuroplasticity. Additionally, this study demonstrates that mice exposed to mSPS and repeated EtOH exposure decreases CB1 in the striatum, providing a mechanism of interest for understanding the effects of EtOH following severe, multimodal stress exposure

    Experiential Learning Through Participatory Action Research in an Interdisciplinary Leadership Training Program

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    Background: Experience in multidisciplinary collaboration among healthcare providers, leaders in public health, and educators is essential to effectively address the diverse needs of children with intellectual and developmental disabilities (I/DD) and their families. Purpose: We describe three participatory action research (PAR) projects from an interdisciplinary training program, which used experiential learning to enhance leadership competencies and promote inclusive services. Trainees report their leadership growth as providers and advocates for children with I/DD using experiential learning through PAR. Approach: Trainees discuss their engagement with organizations serving children with I/DD and ways that experiential learning supported leadership skill development, commitment to inclusive person- and family-centered practices, and contributions to disability advocacy and support programs. Conclusion: PAR is a beneficial experiential learning approach to foster interdisciplinary collaboration through inclusive community engagement. Related training programs may adopt a similar approach to build leadership skills among professionals in health care, public health, and education, and promote optimal health outcomes for children with I/DD

    Anode Biofilm Transcriptomics Reveals Outer Surface Components Essential for High Density Current Production in Geobacter sulfurreducens Fuel Cells

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    The mechanisms by which Geobacter sulfurreducens transfers electrons through relatively thick (>50 µm) biofilms to electrodes acting as a sole electron acceptor were investigated. Biofilms of Geobacter sulfurreducens were grown either in flow-through systems with graphite anodes as the electron acceptor or on the same graphite surface, but with fumarate as the sole electron acceptor. Fumarate-grown biofilms were not immediately capable of significant current production, suggesting substantial physiological differences from current-producing biofilms. Microarray analysis revealed 13 genes in current-harvesting biofilms that had significantly higher transcript levels. The greatest increases were for pilA, the gene immediately downstream of pilA, and the genes for two outer c-type membrane cytochromes, OmcB and OmcZ. Down-regulated genes included the genes for the outer-membrane c-type cytochromes, OmcS and OmcT. Results of quantitative RT-PCR of gene transcript levels during biofilm growth were consistent with microarray results. OmcZ and the outer-surface c-type cytochrome, OmcE, were more abundant and OmcS was less abundant in current-harvesting cells. Strains in which pilA, the gene immediately downstream from pilA, omcB, omcS, omcE, or omcZ was deleted demonstrated that only deletion of pilA or omcZ severely inhibited current production and biofilm formation in current-harvesting mode. In contrast, these gene deletions had no impact on biofilm formation on graphite surfaces when fumarate served as the electron acceptor. These results suggest that biofilms grown harvesting current are specifically poised for electron transfer to electrodes and that, in addition to pili, OmcZ is a key component in electron transfer through differentiated G. sulfurreducens biofilms to electrodes

    Polycystic ovary syndrome and leukocyte telomere length : cross-sectional and longitudinal changes

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    Objective Telomeres are DNA-protein complexes that protect chromosome ends from DNA damage and are surrogate biomarkers of cellular ageing. Current evidence, almost entirely from cross-sectional observations, supports negative associations between leukocyte telomere length (LTL) and adverse lifestyle factors and cardio-metabolic risk factors. Polycystic ovary syndrome (PCOS), the most common gynecological endocrine disorder, is associated with inflammation and oxidative stress, both factors associated with accelerated telomere attrition. We therefore hypothesized that LTL would be shorter and decrease more rapidly in women with PCOS in comparison to a control population. Design Population-based cohort study: women of Northern Finland Birth Cohort 1966, with clinical examinations at ages 31 and 46. The sample included self-reported PCOS (PCOS) (age 31:N=190; age 46:N=207) and referent women (age 31:N=1054; age 46:N=1324) with data on LTL. Methods The association between LTL and PCOS at ages 31 and 46 was analyzed by linear regression models adjusted for BMI, smoking, alcohol consumption and socioeconomic status at the corresponding age. Results Women with PCOS had similar mean LTL at ages 31 and 46 (P>0.4 for both). The mean LTL change between ages 31 and 46 did not differ between groups (P=0.19). However, we observed a significant LTL attrition between ages 31 and 46 in the reference population (P<0.001), but not in women with PCOS (P=0.96). Conclusions This finding may suggest a difference in LTL attrition rate in women with PCOS, an unexpected finding that might affect their risk of age-related disease. Further research is needed to clarify the underlying mechanisms

    Perceptions of Community HIV/STI Risk Among U.S Women Living in Areas with High Poverty and HIV Prevalence Rates

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    Although studies have consistently demonstrated that women at high risk for HIV and non-HIV sexually transmitted infections (STIs) tend to underestimate their individual risk, little is known about how women at risk perceive their community’s HIV/STI risk. We explored perceptions of community HIV/ STI risk among U.S. women living in areas with high poverty and HIV prevalence rates as part of a qualitative substudy of the Women’s HIV SeroIncidence Study. Semi-structured focus groups were conducted. Data were coded and analyzed using the constant comparative method. Participants expressed the perception that their communities were at elevated HIV/STI risk, mostly due to contextual and structural factors such as lack of access to health care and education. Findings suggest that HIV prevention messages that target U.S. women at high risk for HIV may be strengthened by addressing the high perceived community HIV/ STI risk driven by structural factors

    GWAS on longitudinal growth traits reveals different genetic factors influencing infant, child, and adult BMI

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    Early childhood growth patterns are associated with adult health, yet the genetic factors and the developmental stages involved are not fully understood. Here, we combine genome-wide association studies with modeling of longitudinal growth traits to study the genetics of infant and child growth, followed by functional, pathway, genetic correlation, risk score, and colocalization analyses to determine how developmental timings, molecular pathways, and genetic determinants of these traits overlap with those of adult health. We found a robust overlap between the genetics of child and adult body mass index (BMI), with variants associated with adult BMI acting as early as 4 to 6 years old. However, we demonstrated a completely distinct genetic makeup for peak BMI during infancy, influenced by variation at the LEPR/LEPROT locus. These findings suggest that different genetic factors control infant and child BMI. In light of the obesity epidemic, these findings are important to inform the timing and targets of prevention strategies

    Genome-wide Association Analysis in Humans Links Nucleotide Metabolism to Leukocyte Telomere Length

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    Leukocyte telomere length (LTL) is a heritable biomarker of genomic aging. In this study, we perform a genome-wide meta-analysis of LTL by pooling densely genotyped and imputed association results across large-scale European-descent studies including up to 78,592 individuals. We identify 49 genomic regions at a false dicovery rate (FDR) 350,000 UK Biobank participants suggest that genetically shorter telomere length increases the risk of hypothyroidism and decreases the risk of thyroid cancer, lymphoma, and a range of proliferative conditions. Our results replicate previously reported associations with increased risk of coronary artery disease and lower risk for multiple cancer types. Our findings substantially expand current knowledge on genes that regulate LTL and their impact on human health and disease.Peer reviewe
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