Crowdercelik1089

BACKGROUND Cancer is a major cause of death in low- and middle-income countries. A large number of studies have shown that some of the metabolic risk factors (MRFs) tend to cluster in individuals. We examined the synergistic effects of multiple MRFs and cancer risk among Iranian adults. METHODS Among 8593 (3929 men) participants aged ≥ 30 years, the self-organizing map (SOM) was applied to clustering of four MRFs including high fasting plasma glucose (HFPG), high total cholesterol (HTC), high systolic blood pressure (HSBP), and high body mass index (HBMI). The Cox proportional hazards model was used to investigate the association between clusters with cancer incidence during a median of 14.0 years of follow-up. RESULTS During the study period, 265 new cases of cancer were identified among participants at risk. The incidence density rate was 2.5 per 1000 person years in total population. About 32 and 40% of men and women, respectively, had three or four MRFs. We identified seven clusters of MRFs in both men and women. In both genders, MRFs were clustered in those with older age. Further, inverse associations were found between current smoking in men, and education level and passive smoking in women and clustering of MRFs. In men, a cluster with 100% HSBP and HBMI had the highest risk for overall cancer. While, among women, a cluster with 100% HFPG and 93% HBMI yielded the highest risk for cancer. The risk was decreased when HBMI accompanied by HTC. CONCLUSIONS Clustering patterns may reflect underlying link between MRFs and cancer and could potentially facilitate tailored health promotion interventions.BACKGROUND This article reports the effects of proenkephalin (PENK) on osteosarcoma (OS) cell migration. METHODS A Gene Expression Omnibus (GEO) dataset was used to identify differentially expressed genes (DEGs) in OS tumor samples and normal human osteoblasts. Tumor tissue and adjacent normal tissue were collected from 40 OS patients. MG63 cells were transfected with si-PENK. Transwell migration assays and wound healing assays were performed to compare the effect of PENK on migration. Moreover, LY294002 was used to identify the potential mechanism. Gene expression was examined via qRT-PCR and Western blotting. RESULTS Bioinformatic analysis revealed that PENK was downregulated in OS tumor samples compared with normal human osteoblasts. Moreover, PENK was identified as the hub gene of the DEGs. The PI3K/Akt signaling pathway was significantly enriched in the DEGs. Moreover, PENK was downregulated in OS and MG63 cells compared with the corresponding control cells. Silencing PENK promoted MG63 cell migration; however, treatment with LY294002 partially attenuated PENK silencing-induced OS cell migration. CONCLUSION PENK inhibits OS cell migration by activating the PI3K/Akt signaling pathway.BACKGROUND Rates of opioid prescribing tripled in the USA between 1999 and 2015 and were associated with significant increases in opioid misuse and overdose death. Roughly half of all opioids are prescribed in primary care. Although clinical guidelines describe recommended opioid prescribing practices, implementing these guidelines in a way that balances safety and effectiveness vs. risk remains a challenge. The literature offers little help about which implementation strategies work best in different clinical settings or how strategies could be tailored to optimize their effectiveness in different contexts. Systems consultation consists of (1) educational/engagement meetings with audit and feedback reports, (2) practice facilitation, and (3) prescriber peer consulting. The study is designed to discover the most cost-effective sequence and combination of strategies for improving opioid prescribing practices in diverse primary care clinics. METHODS/DESIGN The study is a hybrid type 3 clustered, sequential, muls case to improve opioid prescribing practices in primary care. The blend offers a range of strategies in sequences from minimally to substantially intensive. The results of this study promise to help us understand how to cost effectively improve the implementation of evidence-based practices. find more TRIAL REGISTRATION NCT04044521 (ClinicalTrials.gov). Registered 05 August 2019.BACKGROUND Evidence suggests that sedentary behaviour (SB) is associated with poor health outcomes. SB at any age may have significant consequences for health and well-being and interventions targeting SB are accumulating. Therefore, the need to review the effects of multicomponent, complex interventions that incorporate effective strategies to reduce SB are essential. METHODS A systematic review and meta-analysis were conducted investigating the impact of interventions targeting SB across the lifespan. Six databases were searched and two review authors independently screened studies for eligibility, completed data extraction and assessed the risk of bias and complexity of each of the included studies. RESULTS A total of 77 adult studies (n=62, RCTs) and 84 studies (n=62, RCTs) in children were included. The findings demonstrated that interventions in adults when compared to active controls resulted in non-significant reductions in SB, although when compared to inactive controls significant reductions were foboth children and adults. More needs to be known about how best to optimise intervention effects. Future intervention studies should apply more rigorous methods to improve research quality, considering larger sample sizes, randomised controlled designs and valid and reliable measures of SB.BACKGROUND The ways in which microglia activate and promote neovascularization (NV) are not fully understood. Recent in vivo evidence supports the theory that calcium is required for the transition of microglia from a surveillance state to an active one. The objectives of this study were to discover novel L-type voltage-gated channel (L-VGCC) blockers and investigate their application for the prevention of inflammation and angiogenesis. METHODS Pharmacophore-based computational modeling methods were used to screen for novel calcium channel blockers (CCBs) from the ZINC compound library. The effects of CCBs on calcium blockade, microglial pro-inflammatory activation, and cell toxicity were validated in BV-2 microglial cell and freshly isolated smooth muscle cell (SMC) cultures. Laser-induced choroidal neovascularization (NV) and the suture-induced inflammatory corneal NV models of angiogenesis were used for in vivo validation of the novel CCBs. CX3CR1gfp/+ mice were used to examine the infiltration of GFP-labeled microglial cells.