We estimated that a 1 standard deviation increase in the school average social capital for grade 5 is associated with an odds ratio of .86 (95% credible interval .75-.98) for school-level smoking in grade 10. CONCLUSIONS This study suggests that school social capital in late elementary years is associated with reduced smoking behaviors among adolescents in the U.S. Influencing school social capital through enrichment of positive social norms and parent/teacher expectations may be a useful strategy to reduce adolescent smoking, with long-term implications for adult health. BACKGROUND Preoperative chemotherapy has shown benefits for locally advanced and borderline resectable pancreatic cancer. Neoadjuvant chemotherapy (NAC) has also been attempted in resectable pancreatic cancer (RPC); however, its role remains controversial. This study aimed to compare the clinical difference between NAC and upfront resection (UR) in RPC. METHODS Electronic databases including PubMed, Embase, Medline, Web of Science, ClinicalTrials.gov, and Cochrane Central Register of Controlled Trials were searched for relevant articles from inception to February 2019 that addressed the overall survival in patients with RPC treated with or without NAC to identify eligible studies. Eleven studies were included in the final meta-analysis. The quality assessment of the included studies was based on the Newcastle-Ottawa quality scale. Data of the unresectable rate, R0 resection rate, and positive lymph node rate were also extracted in each study for further analysis. Pooled hazard ratio (HR), odds ratio (OR), andy be associated with a lower resection rate; however, it is associated with an increased R0 resection rate and lymph node negative rate. Although overall survival was similar in patients with or without NAC, gemcitabine-based NAC might provide longer overall survival. Further large-volume, randomized controlled trials are needed to validate the improved prognosis of patients undergoing NAC. Drugs acting on the renin-angiotensin system (RAS) may have beneficial effects on mental health. We investigated whether use of drugs acting on the RAS, as add-on to selective serotonin reuptake inhibitors (SSRIs), was associated with a reduced risk of psychiatric hospital contacts. We identified all individuals initiating treatment with an SSRI between 1997 and 2012. Individuals using an SSRI without concomitant use of a RAS drug (SSRI-only users) were propensity score matched 11 to individuals using both an SSRI and a drug acting on the RAS (SSRI+RAS users). The SSRI-only and SSRI+RAS users were followed for up to three years or until December 31, 2013. We performed Cox proportional hazard regression analyses to calculate risks for psychiatric hospital contacts, hospital contacts due to depression, suicidal behavior, and all-cause mortality. We followed 30,311 SSRI-only users and 30,311 SSRI+RAS users for a total of 49,327 person-years. Compared to SSRI-only users, concomitant use of SSRI+RAS was associated with a significantly reduced risk for psychiatric hospital contacts (hazard rate ratio (HRR)=0.91; 95%-confidence intervals (95%-CI)=0.84-0.98) and lower mortality rate (HRR=0.70; 95%-CI=0.66-0.75). The associations between SSRI+RAS use and psychiatric hospital contacts for depression (HRR=0.92; 95%-CI=0.80-1.05) and suicidal behavior (HRR=1.06; 95%-CI=0.79-1.42) were not statistically significant. In this observational cohort study, concomitant use of an SSRI and a drug acting on the RAS was associated with a slightly reduced risk for psychiatric hospital contacts, when compared to use of an SSRI alone. V.This work explored a novel type of potential multi-targeting antimicrobial three-component sulfanilamide hybrids in combination of pyrimidine and azoles.  https://www.selleckchem.com/products/Temsirolimus.html  The hybridized target molecules were characterized by 1H NMR, 13C NMR and HRMS spectra. Some of the developed target compounds exerted promising antimicrobial activity in comparison with the reference drugs norfloxacin and fluconazole. Noticeably, sulfanilamide hybrid 5c with pyrimidine and indole could effectively inhibit the growth of E. faecalis with MIC value of 1 μg/mL. The active molecule 5c showed low cell toxicity and did not obviously trigger the development of resistance towards the tested bacteria strains. Mechanism exploration indicated that compound 5c could not only exert efficient membrane permeability, but also intercalate into DNA of resistant E. faecalis to form 5c-DNA supramolecular complex, which might be responsible for its antimicrobial action. The further investigation showed that this molecule could be effectively transported by human serum albumins through hydrogen bonds and van der Waals force. Herein, we report the discovery of a series of thieno[2,3-d]pyrimidin-4(3H)-one derivatives as a new class of ROCK inhibitors. Structure-activity relationship studies of these compounds led to the identification of the most potent compound, 3-(3-methoxybenzyl)-6-(1H-pyrrolo[2,3-b]pyridin-4-yl)thieno[2,3-d]pyrimidin-4(3H)-one (8k), which showed IC50 values of 0.004 μM and 0.001 μM against ROCK Ⅰ and ROCK Ⅱ, respectively. In vitro, 8k significantly reduced the phosphorylation level of ROCK downstream signaling protein and induce changes in cell morphology and migration. Overall, this study provides a promising lead compound for drug discovery targeting ROCKs. Toll-like receptors 7 and 8 (TLR7/8) agonists are potent immunostimulants that are attracting considerable interest as vaccine adjuvants. We recently reported the synthesis of a new series of 2-O-butyl-8-oxoadenines substituted at the 9-position with various linkers and N-heterocycles, and showed that TLR7/8 selectivity, potency and cytokine induction could be modulated by varying the alkyl linker length and the N-heterocyclic ring. In the present study, we further optimized the oxoadenine scaffold by investigating the effect of different substituents at the 2-position of the oxoadenine on TLR7/8 potency/selectivity, cytokine induction and DC maturation in human PBMCs. The results show that introducing a 1-(S)-methylbutoxy group at the 2-position of the oxoadenine significantly increased potency for TLR7/8 activity, cytokine induction and DC maturation.