Toftstephansen0446

BACKGROUND Acute glaucoma, characterized by a sudden elevation in intraocular pressure (IOP) and retinal ganglion cells (RGCs) death, is a major cause of irreversible blindness worldwide that lacks approved effective therapies, validated treatment targets and clear molecular mechanisms. We sought to explore the potential molecular mechanisms underlying the causal link between high IOP and glaucomatous RGCs death. METHODS A murine retinal ischemia/ reperfusion (RIR) model and an in vitro oxygen and glucose deprivation/reoxygenation (OGDR) model were used to investigate the pathogenic mechanisms of acute glaucoma. RESULTS Our findings reveal a novel mechanism of microglia-induced pyroptosis-mediated RGCs death associated with glaucomatous vision loss. Genetic deletion of gasdermin D (GSDMD), the effector of pyroptosis, markedly ameliorated the RGCs death and retinal tissue damage in acute glaucoma. Moreover, GSDMD cleavage of microglial cells was dependent on caspase-8 (CASP8)-hypoxia-inducible factor-1α (HIF-1α) signaling. Mechanistically, the newly identified nucleotide-binding leucine-rich repeat-containing receptor (NLR) family pyrin domain-containing 12 (NLRP12) collaborated with NLR family pyrin domain-containing 3 (NLRP3) and NLR family CARD domain-containing protein 4 (NLRC4) downstream of the CASP8-HIF-1α axis, to elicit pyroptotic processes and interleukin-1β (IL-1β) maturation through caspase-1 activation, facilitating pyroptosis and neuroinflammation in acute glaucoma. Interestingly, processing of IL-1β in turn magnified the CASP8-HIF-1α-NLRP12/NLRP3/NLRC4-pyroptosis circuit to accelerate inflammatory cascades. DBZ inhibitor cost CONCLUSIONS These data not only indicate that the collaborative effects of NLRP12, NLRP3 and NLRC4 on pyroptosis are responsible for RGCs death, but also shed novel mechanistic insights into microglial pyroptosis, paving novel therapeutic avenues for the treatment of glaucoma-induced irreversible vision loss through simultaneously targeting of pyroptosis.BACKGROUND Leadership and management training has become increasingly important in the education of health care professionals. Previous research has shown the benefits that a network provides to its members, such as access to resources and information, but ideas for creating these networks vary. This study used social network analysis to explore the interactions among Central American Healthcare Initiative (CAHI) Fellowship alumni and learn more about information sharing, mentoring, and project development activities among alumni. The CAHI Fellowship provides leadership and management training for multidisciplinary healthcare professionals to reduce health inequities in the region. Access to a network was previously reported as one of the top benefits of the program. RESULTS Information shared from the work of 100 CAHI fellows from six countries, especially within the same country, was analyzed. Mentoring relationships clustered around professions and project types, and networks of joint projects clustered by country. Mentorship, which CAHI management promoted, and joint project networks, in which members voluntarily engaged, had similar inclusiveness ratios. CONCLUSION Social networks are strategic tools for health care leadership development programs to increase their impact by promoting interactions among participants. These programs can amplify intergenerational and intercountry ties by organizing events, provide opportunities for alumni to meet, assign mentors, and support collaborative action groups. Collaborative networks have great value to potentiate health professionals' leadership and management capabilities in a resource-constrained setting, such as the Global South.BACKGROUND Lifestyle interventions to prevent paediatric obesity often target family and peer settings; their success is likely to depend on the influence that peers and families exert on children's lifestyle behaviors at different developmental stages. OBJECTIVE First, to determine whether children's lifestyle behavior more closely resembles their peers' or siblings' behaviors. Secondly, to investigate longitudinally whether children's behavioral change is predicted by that of their peers or their siblings as they grow older. METHODS The European prospective IDEFICS/I.Family cohort (baseline survey 2007/2008, first follow-up 2009/2010, and second follow-up 2013/2014) aims at investigating risk factors for overweight and related behaviors during childhood and adolescence. The present investigation includes 2694 observations of children and their siblings aged 2 to 18 years. Peers were defined as same-sex, same-age children in the same community and identified from the full cohort. The longitudinal analysis (mon were more strongly associated with those in their peer group than their sibling, in particular if the age gap between siblings was large. CONCLUSION In conclusion, our results support the implementation of multi-setting interventions for improving lifestyle behaviors in children. Our findings might also guide future intervention studies in the choice of timing and setting in which interventions are likely to be most effective. From the ages of 9-10 years onwards, family- or home-based interventions targeting children's fast food intake and screen time behavior may become less effective than school- or community-based interventions aimed at peer groups.BACKGROUND Patient-reported outcomes measures, such as those provided by the Psoriatic Arthritis Impact of Disease (PsAID) questionnaire, have been found to be a reliable indicator of change during treatment, predictive of long-term outcomes, and the impact of psoriatic arthritis (PsA) on patients' lives. The objective of the study was to describe the demographic and clinical characteristics of PsA patients with a low disease impact and to analyze predictive factors for that state. METHODS Post hoc analysis of a cross-sectional multicenter study that included 223 consecutive patients. PsAID questionnaire was used to estimate disease impact. Patients with a PsAID less then  4 were considered in low disease impact. Minimal disease activity (MDA) response and the Health Assessment Questionnaire (HAQ) were also assessed. The degree of agreement between the different outcomes was addressed by Cohen's kappa index. RESULTS One hundred and twenty-two (54.7%) patients reached a PsAID less then  4. Among them, 52.0% and 68.