Juglanin significantly reduced cellular oxidative stress by downregulating NOX4 expression production and rescuing the decreased activity of total SOD induced by LPS. Juglanin inhibited the activation of the TxNIP/NLRP3/ASC/caspase-1 axis, and decreased production of IL-1β and IL-18. Moreover, juglanin rescued the LPS-induced decrease in SIRT1 expression. SIRT1 silencing abolished the anti-NLRP3 inflammasome effect of juglanin, indicating that the effects of juglanin are dependent on its amelioration on SIRT1 expression. Juglanin possesses an anti-inflammatory and anti-ROS capacity in chondrocytes, and this study provides available evidence that juglanin may be of use in the treatment of arthritis.
  Gamma Knife radiosurgery (GKRS) inverse dose planning is currently far from competing effectively with the quality of dose planning developed by experienced experts. A new inverse planning (IP) method based on « efficient convex optimization algorithms » is proposed, providing high-quality dose plans in real time.
 
  Eighty-six patients treated by GKRS for vestibular schwannomas (VS) were recruited. The treatment plans created by the first author, who has 27 years of experience and has developed and delivered more than 15,000 dose plans, served as reference. A first set of basic constraints determined by default led the IP for an initial real-time dose plan. Additional constraints were interactively proposed by the planner to take other parameters into account. A second optimized plan was then calculated by the IP. The primary endpoint was the Paddick Conformity Index (PCI). The statistical analysis was planned on a non-inferiority trial design. Coverage, selectivity, and gradient indexes, dose at the organ(mpete in real time with the quality of the treatment plans of an expert with extensive radiosurgical experience, this could allow new planners/radiosurgeons with limited or no experience to immediately provide patients with high-quality GKRS for benign and malignant lesions.
 These preliminary results showed that this new IP method based on « efficient convex optimization algorithms », called IntuitivePlan®, provided high-quality dose plans in real time with excellent coverage, selectivity, and gradient indexes with optimized beam-on time. If the new IP evaluated here is able to compete in real time with the quality of the treatment plans of an expert with extensive radiosurgical experience, this could allow new planners/radiosurgeons with limited or no experience to immediately provide patients with high-quality GKRS for benign and malignant lesions.
  The cumulative intracranial tumor volume (CITV) has recently been suggested to be a more relevant predictive factor for patients with brain metastases (BM) treated with stereotactic radiosurgery (SRS). We aimed to investigate the feasibility of upfront SRS for patients with BM having a high CITV, i.e., exceeding 7ml.
 
  Two hundred thirty-three consecutive patients with BM having a CITV > 7ml who underwent SRS as first-line treatment from 2011 to 2019 were retrospectively identified. The overall survival (OS) and intracranial disease control rates were analyzed. Multivariate proportional hazards models were used to identify prognostic factors associated with treatment outcome. Toxicity and salvage therapy were also investigated.
 
  The median OS was 8.7months (95% confidence interval 7.1-10.4), and 6-month and 1-year OS rates were 60 and 40%, respectively. Systemic anticancer therapy (hazard ratio (HR) 0.45, p < 0.001), female sex (HR 0.61, p = 0.001), synchronous SRS (HR 0.57, p = 0.003), number of BM (HR 1.04, p = 0.008), controlled extracranial disease (HR 0.56, p = 0.009), Karnofsky performance status (HR 0.87, p = 0.015), and staged SRS (HR 0.71, p = 0.037) were found to be factors independently associated with OS. Post-SRS toxicities of CTCAE grades 3, 4, and 5 were observed in 14, 5, and 1 patient, respectively. As salvage management, repeat SRS, whole brain radiotherapy, and surgical resection were required for 84, 16, and 10 patients, respectively, CONCLUSIONS With vigilant surveillance and appropriate salvage management, upfront SRS alone can be considered as a relatively safe and effective treatment strategy even for BM with CITV > 7ml.
  7 ml.Treating mental illnesses in primary care is increasingly emphasized to improve access to mental health services. Although family physicians (FPs) or general practitioners are in an ideal position to provide the bulk of mental health care, it is unclear how best to remunerate FPs for the adequate provision of mental health services. We examined the quantity of mental health services provided in Ontario's blended fee-for-service and blended capitation models. We evaluated the impact of FPs switching from blended fee-for-service to blended capitation on the provision of mental health services in primary care and emergency department using longitudinal health administrative data from 2007 to 2016. We accounted for the differences between those who switched to blended capitation and non-switchers in the baseline using propensity score weighted fixed-effects regressions to compare remuneration models. We found that switching from blended fee-for-service to blended capitation was associated with a 14% decrease (95% CI 12-14%) in the number of mental health services and an 18% decrease (95% CI 15-20%) in the corresponding value of services. This result was driven by the decrease in services during regular-hours. During after-hours, the number of services increased by 20% (95% CI 10-32%) and the corresponding value increased by 35% (95% CI 17-54%). Switching was associated with a 4% (95% CI 1-8%) decrease in emergency department visits for mental health reasons. Blended capitation reduced provision of mental health services without increasing emergency department visits, suggesting potential efficiency gain in the blended capitation model in Ontario.
  Gliomas represent about 80% of primary brain tumours and about 30% of malignant ones, which today don't have a resolution therapy because of their variability. A valid model for the study of new personalized therapies can be represented by primary cultures from patient's tumour biopsies.
 
  In this study we consider 12 novel cell lines established from patients' gliomas and immunohistochemically and molecularly characterized according to the newly updated 2016 CNS Tumour WHO classification.
 
  Eight of these lines were glioblastoma cells, two grade III glioma cells (anaplastic astrocytoma and oligo astrocytoma) and two low grade glioma cells (grade II astrocytoma and oligodendroglioma). All cell lines were analysed by immunohistochemistry for specific glioma markers, respectively VIMENTIN, GFAP, IDH1R132, and ATRX.  https://www.selleckchem.com/products/iso-1.html  The methylation status of the MGMT gene promoter was also determined in all lines. The comparison of the immunohistochemical characteristics and of the MGMT methylation status of the lines with the tissues of origin shows that the cells in culture maintain the same characteristics.