Notes

Melatonin attenuates reduced shear stress-induced pyroptosis and endothelial mobile dysfunction through RORα/miR-223/STAT-3 signalling pathway.
In this review, we discuss how epigenetic factors control the expression of genes such as Fgf8 that are known to be critical for GnRH neurone ontogenesis, fate specification, and the pathogenesis of KS/CHH.Four pivotal randomized placebo-controlled trials have demonstrated that adjunctive therapy with cannabidiol (CBD) improves seizure control in patients with Dravet syndrome (DS) and Lennox-Gastaut syndrome (LGS). Between 47% and 68% of patients allocated to CBD treatment in these trials were receiving clobazam (CLB), which shows complex interactions with CBD resulting, in particular, in a 3.4- to 5-fold increase in plasma concentration of the active metabolite norclobazam. This raises concern as to the role played by these interactions in determining the reduction in seizure frequency in CBD-treated patients, and the question of whether CBD per se has clinically evident antiseizure effects. find more We appraised available evidence on the clinical consequences of the CBD-CLB interaction, focusing on subgroup analyses of seizure outcomes in patients on and off CLB comedication in the pivotal CBD trials, as provided by the European Medicines Agency Public Assessment Report. Evaluation of the results of individual trials clearly showed that improvement in seizure control over placebo was greater when CBD was added on to CLB than when it was added on to other medications. However, seizure control was also improved in patients off CLB, and despite the small sample size the difference vs placebo was statistically significant for the 10 mg/kg/d dose in one of the two LGS trials. Stronger evidence for an antiseizure effect of CBD independent of an interaction with CLB emerges from meta-analyses of seizure outcomes in the pooled population of LGS and DS patients not receiving CLB comedication. Although these results need to be interpreted taking into account methodological limitations, they provide the best clinical evidence to date that CBD exerts therapeutic effects in patients with epilepsy that are independent of its interaction with CLB. Greater antiseizure effects, and a greater burden of adverse effects, are observed when CBD is combined with CLB.Lung, colorectal, and breast cancers are the top three types of cancer by incidence and are responsible for one-third of the cancer incidence and mortality. A series of 18 3,4-dihydropyrimidine analogues bearing a 1,2-methylenedioxybenzene component at position 4 with diverse side chains at positions 5 and 6 was designed and synthesized as inhibitors of the Eg5 kinesin enzyme. Target compounds were screened for their anticancer activity according to the NCI-USA protocol toward a panel of 60 cancer cell lines. Compounds 12a and 12b displayed the best antiproliferation activity against many cell lines. Interestingly, compound 12a displayed lethal effects against non-small-cell lung cancer NCI-H522 cells (-42.26%) and MDA-MB-468 breast cancer cells (-1.10%) at a single-dose assay concentration of 10-5 M. Compounds 11c, 11d, 11g, 12a-d, 13, 15, and 18a were assayed against the kinesin enzyme, with IC50 values ranging from 1.2 to 18.71 μM, which were more potent compared with monastrol (IC50 = 20 μM). Cell cycle analysis of NCI-H522 cells treated with compound 12a showed cell cycle arrest at the G2/M phase. Furthermore, the expression levels of active caspase-3 and -9 were measured. A molecular docking study was performed for some demonstrative compounds as well as monastrol docked into the allosteric binding site of the kinesin spindle protein.Pervasive cultural narratives that normalize domestic violence have made efforts to respond to domestic violence in India challenging. An effective response to domestic violence in India needs to be transformative in nature, supporting the empowerment of survivors of violence and empowering communities to support survivors. Various studies have highlighted the importance of settings like grassroots organizations for promoting empowerment of members through community organizing. This qualitative study builds on this growing body of research using a grassroots agency in India as an exemplar to understand (a) empowering processes at the individual and community level associated with the agency's community organizing efforts; and (b) salient mechanisms associated with social change and action in the response to domestic violence in the community. At the individual level, the agency's organizing efforts provided knowledge, skills and resources, and opportunities for participation and leadership. At the community level, the agency engages in capacity building and increases social capital of members. The mechanisms that emerged as salient were increased critical consciousness of members, an emphasis on breaking the silence around domestic violence, community trust and cohesion, and capacity for informal social control. Implications of our findings for intervention and prevention work are discussed. HIGHLIGHTS Community organizing is an important avenue for change in the response to domestic violence. Community organizing can facilitate empowering processes like participation and leadership. Building capacity and social capital is central to facilitating empowerment of communities.Background The Self Assessment Vitiligo Extent Score (SA-VES) is a validated, patient reported outcome measure to assess the body surface area affected with vitiligo. Information on how to translate the obtained score into extent, severity and impact strata (mild-moderate-severe) is still lacking. Stratification is helpful to define inclusion criteria for trials, enables comparison and pooling of trial results and can be used for epidemiological research. Objectives The aim was to develop extent, severity and impact strata for the SA-VES based on validated anchor based questions. Methods In total, 316 patients with vitiligo (non-segmental; age ≥16) recruited at the Ghent University Hospital (Belgium) completed a questionnaire that was conducted in cooperation with the Dutch Society for Vitiligo patients to ensure content validity. First 3 anchor questions included in the questionnaire [Patient Global Assessment (PtGA) for vitiligo extent, severity and impact] were assessed for content validity, construct validity and intrarater reliability.
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