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These inductions were abolished by NLRP3 deficiency in DCs, suggesting that NLRP3 in MLES-treated DCs plays a role in promoting the Th2 and Treg response. selleck kinase inhibitor Taken together, we identified for the first time the involvement of NLRP3 in host defences against T. spiralis.

Synovitis-associated pain is mediated by inflammatory factors that may include S100A8/9, which is able to stimulate nociceptive neurons via Toll-like receptor 4. In this study, we investigated the role of S100A9 in pain response during acute synovitis.

Acute synovitis was induced by streptococcal cell wall (SCW) injection in the knee joint of C57Bl/6 (WT) and S100A9

mice. The expression of S100A8/A9 was determined in serum and synovium by ELISA and immunohistochemistry. Inflammation was investigated by

Tc accumulation, synovial cytokine release, and histology at days 1, 2, and 7. To assess pain, weight distribution, gait analysis, and mechanical allodynia were monitored. Activation markers in afferent neurons were determined by qPCR and immunohistochemistry in the dorsal root ganglia (DRG). Differences between groups were tested using a one-way or two-way analysis of variance (ANOVA). Differences in histology were tested with a non-parametric Mann-Whitney U test. p values lower than 0.05 were considering the acute phase of inflammation.

Gambling and problem gambling are increasingly being viewed as a public health issue. European surveys have reported a high prevalence of gambling, and according to the Gambling Commission, in 2018, almost half of the general population aged 16 and over in England had participated in gambling in the 4 weeks prior to being surveyed. The potential harms associated with gambling and problem are broad, including harms to individuals, their friends and family, and society. There is a need to better understand the nature of this issue, including its risk factors. The purpose of this study is to identify and examine the risk factors associated with gambling and problem gambling.

An umbrella review will be conducted, where systematic approaches will be used to identify, appraise and synthesise systematic reviews and meta-analyses of risk factors for gambling and problem gambling. The review will include systematic reviews and meta-analyses published between 2005 and 2019, in English language, focused on any population and any risk factor, and of quantitative or qualitative studies. Electronic searches will be conducted in Ovid MEDLINE, Ovid Embase, Ovid PsycInfo, NICE Evidence and SocIndex via EBSCO, and a range of websites will be searched for grey literature. Reference lists will be scanned for additional papers and experts will be contacted. Screening, quality assessment and data extraction will be conducted in duplicate, and quality assessment will be conducted using AMSTAR-2. A narrative synthesis will be used to summarise the results.

The results of this review will provide a comprehensive and up-to-date understanding of the risk factors associated with gambling and problem gambling. It will be used by Public Health England as part of a broader evidence review of gambling-related harms.

PROSPERO CRD42019151520.

PROSPERO CRD42019151520.

Glaucoma is a leading neurodegenerative disease affecting over 70 million individuals worldwide. Early pathological events of axonal degeneration and retinopathy in response to elevated intraocular pressure (IOP) are limited and not well-defined due to the lack of appropriate animal models that faithfully replicate all the phenotypes of primary open angle glaucoma (POAG), the most common form of glaucoma. Glucocorticoid (GC)-induced ocular hypertension (OHT) and its associated iatrogenic open-angle glaucoma share many features with POAG. Here, we characterized a novel mouse model of GC-induced OHT for glaucomatous neurodegeneration and further explored early pathological events of axonal degeneration in response to elevated IOP.

C57BL/6 J mice were periocularly injected with either vehicle or the potent GC, dexamethasone 21-acetate (Dex) once a week for 10 weeks. Glaucoma phenotypes including IOP, outflow facility, structural and functional loss of retinal ganglion cells (RGCs), optic nerve (ON) degeneratitial stages of axonal degeneration (30% loss) and complete transport deficits were only observed at the ONH during later stages of severe axonal degeneration (50% loss).

These findings indicate that ON degeneration and transport deficits at the ONH precede RGC structural and functional loss and provide a new potential therapeutic window for rescuing neuronal loss and restoring health of damaged axons in glaucoma.

These findings indicate that ON degeneration and transport deficits at the ONH precede RGC structural and functional loss and provide a new potential therapeutic window for rescuing neuronal loss and restoring health of damaged axons in glaucoma.An amendment to this paper has been published and can be accessed via the original article.

Philanthropists, charity leaders and policy-makers have increasingly recognised that the process of giving resources needs to be grounded in evidence-sometimes referred to as ‘evidence-based’ or ‘data-driven’ philanthropy. Yet few philanthropists practise evidence-based philanthropy, and some contend that there is insufficient evidence on which to base their funding decisions. This review aims to identify factors that promote or limit the use of evidence by philanthropists and to rigorously evaluate all existing research on this issue.

To identify, synthesise, and evaluate appropriate and rigorous research, examining factors which act as barriers to or facilitators of the use of evidence by philanthropists.

This review was conducted according to Cochrane standards and reported following PRISMA guidelines. The review protocol was pre-registered ( dx.doi.org/10.17504/protocols.io.wbsfane ). We searched 10 interdisciplinary databases using a highly sensitive search strategy, developed in consultation with eration of ‘all available evidence’. Finally, there should be more investment in synthesizing evidence and in the infrastructure for knowledge transfer.