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    MS vs. NMS had decreased accuracy on CPT and MPT and efficiency during Stroop. No significant effects of cigarette type preference by menthol or nicotine were found for any task. Significant effects of nicotine by menthol were found during Stroop, where participants had greater accuracy for high nicotine compared to saline during the low menthol session. Significant effects of menthol by timepoint were seen during Stroop, where participants improved across timepoints during the low menthol session. Findings did not support significant effects of inhaled menthol, alone or with nicotine, on cognitive performance. Further research clarifying the impact of varying menthol and nicotine levels in nicotine products may help to elucidate menthol’s role in smoking sustainment.

    Screening adolescents at risk for cannabis use disorders is critical. The CRAFFT is a screening tool designed to address both alcohol and drug use among youth. Current study tests the psychometric properties of the CRAFFT and attempts to modify one of the screening items to compare the efficiency.

    We examined the ideal cut-off point of the CRAFFT for identifying persons with heavy cannabis use and compared the utility of the original and revised CRAFFT.

    Sample (N=132,555) averaged 16.19 (±1.21) years of age; 51.0% were female, 59.7% were White, 15.2% were Latino/Latina, and 6.7% were African-American. Majority resided in non-rural area and 34.5% were receiving free or reduced lunch at school.

    Heavy cannabis use was defined as using cannabis 10 or more times in the past 30days. Sensitivity, specificity, the area under the receiver operating characteristic curve, and Youden value were analyzed to determine the ideal cut-off point.

    Maximum overall predictive accuracy was at a cutoff score of 2 or higher when using the original CRAFFT questions. At a cutoff score of 2, sensitivity was 82.0%, specificity was 83.7%, with an AUC of 0.880. On the contrary, when an alternative CAR question was used, maximum predictive accuracy was at a cutoff score of 1 or higher when predicting heavy cannabis use. At a cutoff score of 1, sensitivity was 92.7%, specificity was 75.5%, with an AUC of 0.900.

    The results provide evidence that the CRAFFT is a promising brief diagnostic instrument for heavy cannabis use among youth. Modification to Car item may have potential in reducing disparities in sensitivity among different racial ethnic groups, as well as those who with low socioeconomic status.

    The results provide evidence that the CRAFFT is a promising brief diagnostic instrument for heavy cannabis use among youth. Modification to Car item may have potential in reducing disparities in sensitivity among different racial ethnic groups, as well as those who with low socioeconomic status.The poor outcomes in ovarian cancer necessitate new treatments. Strategies to interfere with oxidative phosphorylation have been recently highlighted for the treatment of ovarian tumors. Atovaquone, an approved antimicrobial drug, has demonstrated anti-cancer potential and ability in disrupting mitochondrial function. Here, we investigated the efficacy of atovaquone as single drug and its combination with cisplatin in ovarian cancer. We show that atovaquone at clinically achievable concentrations is active against ovarian cancer bulky and stem-cell like cells via inhibiting growth and colony formation, and inducing caspase-dependent apoptosis. In contrast, atovaquone either does not or inhibits normal cells in a less extent than in ovarian cancer cells. Mechanism studies using multiple independent approaches demonstrate that atovaquone acts on ovarian cancer cells via decreasing mitochondrial complex III which results in mitochondrial respiration inhibition, energy reduction and oxidative stress. In line with in vitro findings, atovaquone alone at non-toxic dose is effective in inhibiting ovarian cancer growth in vivo, and its combination with cisplatin is synergistic. Our study suggests that atovaquone is a promising candidate to the treatment of ovarian cancer. buy Cyclopamine Our work also supports the notion that mitochondrial respiration is a therapeutic target in ovarian cancer.

    It is reportedly demonstrated that miR-135a-5p plays a critical role in cancer cells, macrophages, and endothelia cells. However, little is known concerning the function of miR-135a-5p in vascular smooth muscle cells (VSMCs) and atherosclerosis (AS).

    Human VSMCs and male C57BL/6 mice were used for establishing AS cell models and animal models. Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to detect the expressions of miR-135a-5p, forkhead box O1 (FOXO1) mRNA, and Janus kinase 2 (JAK2) mRNA. CCK-8, BrdU, and Transwell assays were used to detect cell migration and proliferation. Cell cycle and apoptosis were analyzed using flow cytometry. The interactions among miR-135a-5p, FOXO1 and JAK2 were validated employing Western blot, qRT-PCR and Luciferase reporter gene assay.

    The expression of miR-135a-5p was significantly decreased in serum samples of AS patients, VSMCs treated with ox-LDL and AS mice models. The overexpression of miR-135a-5p induced VSMCs cycle arrest and apoptosis, and inhibited proliferation and migration. Further experiments confirmed that miR-135a-5p could target and repress FOXO1/CyclinD1 and JAK2/STAT3 pathway. Additionally, the associations among miR-135a-5p, FOXO1/Cyclin D1 and JAK2/STAT3 were validated using animal models.

    MiR-135a-5p suppresses VSMCs proliferation and migration induced by ox-LDL via targeting and activating FOXO1/Cyclin D1 and JAK2/STAT3 signaling pathways.

    MiR-135a-5p suppresses VSMCs proliferation and migration induced by ox-LDL via targeting and activating FOXO1/Cyclin D1 and JAK2/STAT3 signaling pathways.

    Pain, anxiety, and depression (PAD) are common, co-occurring symptoms that adversely affect one another and may respond to common treatments. PAD composite measures would be useful for tracking treatment response in patients with PAD symptoms. The goal of this study is to compare 3 different PAD composite scales in terms of construct validity, responsiveness, and utility in predicting global improvement.

    The sample consisted of 294 primary care patients enrolled in a telecare trial for treating pain, anxiety, and depression. Assessments at baseline and 3months included the Brief Pain Inventory, PHQ-9 depression scale, GAD-7 anxiety scale, PROMIS measures, Medical Outcomes Study Short-Form items, disability measures, and patient-reported global improvement. Construct validity of the PAD composite measures, their responsiveness, and their ability to predict global improvement was analyzed using Pearson correlations, standardized response means, and receiver operating characteristics analysis.

    PAD composite measures correlated strongly with one another, and moderately with measures of function, vitality, and disability.

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