Quinngalbraith9802

PPARα and PPARγ play important roles in regulating glucose and lipid metabolism. In recent years, the development of dual PPAR agonists has become a hot topic in the field of anti-diabetic medicinal chemistry. The dual PPARα/γ agonists can both improve metabolism and reduce side effects caused by single drugs, and has become a promising strategy for designing effective drugs for the treatment of type 2 diabetes. In this study, by means of virtual screening, molecular docking and ADMET prediction technology, a representative compound with higher docking score, lower toxicity than original ligands was gained from the Ligand Expo Components database. It was observed through MD simulation that the representative compound not only has the function of activating the PPARα target and the PPARγ target, but also show a more favorable binding mode when the representative compound binds to the two receptors compared to the original ligands. Our results provided an approach to rapidly find novel PPARα/γ dual agonists for the treatment of type 2 diabetes mellitus (T2DM).This paper explores novel compounds targeting PPARα/γ dual agonists by using molecular docking, ADMET prediction, and molecular dynamics simulation methods. The specific flowchart is as follows HighlightsThe results show that the skeleton of compound M80 is not only similar to Saroglitazar but also higher than that of Saroglitazar in activity.This study explained the binding modes of saroglitazar-PPARα/γ complexes and provided structure reference for the research and development of novel PPARα/γ dual agonists.Communicated by Ramaswamy H. Sarma.Objective In the real-world environment, multiple and interacting state-dependent factors (e.g., fatigue, distractions) can cause cognitive failures and negatively impact everyday activities. This study used ecological momentary assessment (EMA) and a n-back task to examine the relationship between fluctuating levels of cognition measured in the real-world environment and self-report and performance-based measures of functional status.Method Thirty-five community-dwelling older adults (M age = 71.80) completed a brief battery of objective and self-report measures of cognitive and functional status. After completing 100, 45-second trials to reach stable performance on a n-back task, EMA data collection began. Four times daily for one week, participants received prompts on a tablet to complete a n-back task and a brief survey. From the EMA n-back trials, measures of EMA average performance and intra-individual variability (IIV) across performances were created.Results For the EMA n-back, the correlation between IIV and EMA average was weak and non-significant. IIV associated with self-report measures, and EMA average with the objective, performance-based functional status composite. Hierarchical regressions further revealed that IIV was a significant predictor of self-reported functional status and cognitive failures over and above EMA average performance and global cognitive status. In contrast, for the objective, functional status composite, IIV did not explain additional variance.Conclusions The findings suggest that IIV and self-report measures of functional status and cognitive failures may capture a real-world cognitive capacity that fluctuates over time and with context; one that may not easily be captured by objective, performance-based measures designed to assess optimal function.BACKGROUND Professors of nursing sometimes experience specific situations in their daily practice that conflict with their values and ethical principles and may culminate in moral distress. Moral distress occurs when one is prevented from acting according to his or her knowledge or values, or what one considers to be ethically sound. OBJECTIVES To identify the profile of professors of nursing through grouping sociodemographic characteristics and intensity of moral distress. METHOD Cross-sectional and exploratory study addressing 373 nurses teaching in Brazilian federal public higher education institutions. Data were collected from June to December 2018 through email, using the Google Docs tool. Asunaprevir solubility dmso A moral distress scale directed to nurse educators was used. Data were analyzed using descriptive statistics, variance analysis, and cluster analysis. ETHICAL CONSIDERATIONS The Institutional Review Board at the Federal University of Rio Grande approved this study. FINDINGS Initially, four clusters emerged for each variable predicting the profile of Brazilian professors of nursing sex; whether the individual worked in a graduate program; age; experience in years in their respective higher education institution; and intensity of moral distress. The profile of Brazilian professors of nursing was represented by the largest cluster, 36.5% (n = 136), composed of women working in graduate programs, aged 37 years old on average, having worked in their respective institutions for approximately 5 years, and presenting a moderate intensity of moral distress. CONCLUSION Assigning individuals into groups facilitates seeing similarities among the predictors that compose the profile of Brazilian professors of nursing, thus recognizing those workers experiencing moral distress in their daily work routine. In addition, this study's results are expected to encourage reflection on the planning of efficacious interventions directed to the context of education and health.Objective Patients with Korsakoff's syndrome (KS) show executive dysfunction and neuropsychiatric symptoms. This study investigates whether specific executive subcomponents (shifting, updating, and inhibition) predict variance in neuropsychiatric symptoms. We hypothesized that shifting deficits, in particular, are associated with neuropsychiatric symptoms.Method Forty-seven patients participated (mean age 61.5; 11 women). Executive function (EF) was measured using six component-specific tasks. Neuropsychiatric symptoms were measured with the Neuropsychiatric Inventory - Questionnaire (NPI-Q). General cognitive functioning was assessed with the Montreal Cognitive Assessment (MoCA). First, factor analysis was conducted to examine shared variance across the EF tasks. Subsequently, a regression analysis was performed with the EF factors and the MoCA as predictors and the NPI-Q as the dependent variable. It was also investigated whether an interaction effect between the EF factors and the MoCA was present.Results The prevalence of neuropsychiatric symptoms was high (85.