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Ford Doherty posted an update 4 hours, 5 minutes ago
PURPOSE To investigate whether non-allergic rhinitis among the elderly was associated with living close to mine dumps METHODS Elderly persons (n = 2397) residing in communities 1-2 km (exposed) and ≥ 5 km (unexposed) from five preselected mine dumps in Gauteng and North West provinces in South Africa were included in the cross-sectional study, using a previously validated modified ATS-DLD-78 questionnaire from the British Medical Research Council. RESULTS The overall prevalence of non-allergic rhinitis in this study was 23.99%. In the unexposed, it was found to be 18.82% and 27.08% exposed communities. Multiple logistic regression analysis indicated that having non-allergic rhinitis was significantly associated with living in exposed communities (OR 1.73; 95% CI 1.37-2.17), being an ex-smoker (OR 1.75; 95 CI 1.35-2.26), being a smoker (OR 1.24; 95% CI 1.02-1.62), history of occupational exposure to dust/chemical fumes (OR 1.58; 1.30-1.93) and use of gas as the main residential heating/cooking fuel type (OR 1.61; 1.01-2.57). CONCLUSION A high prevalence of non-allergic rhinitis was observed in the elderly living in exposed communities. The adverse association was observed between residing in communities close to mine dumps and non-allergic rhinitis.About 33% patients with osteoarthritis undergoing total hip/knee arthroplasty are not satisfied with the outcome, warranting the need to improve patient selection. Handgrip strength (HGS) has been suggested as a proxy for overall muscle strength and may be associated with post-arthroplasty function. This study aims to assess the association of pre-operative HGS with change in hip/knee function and quality of life in patients with arthroplasty. 226 hip (THA) and 246 knee (TKA) arthroplasty patients were included in this prospective cohort study. Pre-operative HGS was assessed by means of a dynamometer and the HOOS/KOOS and SF-36 questionnaires were collected before arthroplasty and 1 year thereafter. The association of HGS with score change on each sub-domain of the included questionnaires was assessed by linear regression models, adjusting for sex, body mass index and baseline score. Mean pre-operative HGS was 26 kg for patients undergoing THA and 24 kg for those undergoing TKA. HGS was positively associated with an increased improvement score on “function in sport and recreation”-domain in hip (β = 0.68, P = 0.005) and knee (β = 0.52, P = 0.049) and “symptoms”-domain in hip (β = 0.56, P = 0.001). For patients with THA, HGS was associated with the “quality of life” domain (β = 0.33, P = 0.033). In patients with TKA, HGS was associated with the physical component score (β = 0.31, P = 0.001). All statistically significant effects were positive, indicating that with greater pre-operative HGS, an increased gain in 1-year post-surgery score was observed. HGS can be used as a tool to inform patients with OA who are future candidates for a prosthesis about the possible improvements of certain aspects of life after arthroplasty.Necrosis with inflammation plays a crucial role in acute respiratory distress syndrome (ARDS). Receptor-interacting protein 3 (RIPK3) regulates a newly discovered programmed form of necrosis called necroptosis. However, the underlying mechanism of necroptosis in ARDS remains unknown. Thus, the purpose of this study was to examine the possible involvement of RIPK3 in ARDS-associated necroptosis. RIPK3 protein levels were found to be significantly elevated in the plasma and bronchoalveolar lavage fluid of ARDS patients. Next, we utilised a mouse model of severe ARDS induced with high-dose lipopolysaccharide and found that lung injury was mainly due to RIPK3-mixed lineage kinase domain-like pseudokinase (MLKL)-mediated necroptosis and endothelial dysfunction. The activation of RIPK3-MLKL by tumour necrosis factor receptor 1 (TNFR1) and TNFR1-associated death domain protein (TRADD) required catalytically active RIPK1 and the inhibition of Fas-associated protein with death domain (FADD)/caspase-8 catalytic activity. We further showed that the molecular chaperone heat shock protein 90 (Hsp90)/p23, as a novel RIPK3- and MLKL-interacting complex, played an important role in RIP-MLKL-mediated necroptosis, inflammation and endothelial dysfunction in the pulmonary vasculature, which resulted in ARDS. Collectively, the results of our study indicate that necroptosis is an important mechanism of cell death in ARDS and the inhibition of necroptosis may be a therapeutic intervention for ARDS. KEY MESSAGES Lung injury in high-dose LPS-induced severe ARDS is mainly due to RIP3-MLKL-mediated necroptosis and endothelial dysfunction. Chaperone HSP90/p23 is a novel RIP3- and MLKL-interacting complex in HPAECs. HSP90/p23 is a novel RIP3- and MLKL-interacting complex in RIP-MLKL-mediated necroptosis, inflammation and endothelial dysfunction.Embryo implantation is an essential and complex process in mammalian reproduction. However, little evidence has indicated the involvement of autophagy during embryo implantation. To determine the possible role of autophagy in uterine of pregnant mice during the peri-implantation stage, we first examined the expression of autophagy-related markers ATG5 and LC3 on day 4, 5, and 6 of pregnancy (D4, D5, and D6, respectively). Compared with expression on D4, downregulation of the autophagy-related markers was observed on D5 and D6, the days after the embryo attached to the receptivity endometrium. Further examination showed that autophagy-related markers ATG5, ATG12, LC3, cathepsin B, and P62 at the implantation site were significantly decreased when comparing with the inter-implantation site. Fewer number of autophagosomes at the implantation site were also observed by transmission electron microscopy. To confirm the functional role of autophagy during embryo implantation in mice, we administered the autophagy inhibitor 3-methyladenine and chloroquine to mice. selleck kinase inhibitor After treated with 3-methyladenine, the expression of decidual markers HOXA10 and progesterone receptor were significantly reduced. Furthermore, a reduction in implantation sites and increase in the HOXA10 and PR protein levels were observed in response to chloroquine treatment. In addition, impaired uterine decidualization and dysregulation of the PR and HOXA10 protein levels was observed after autophagy inhibited by 3-methyladenine and chloroquine in in vivo artificial decidualization mouse model. In the last, LC3 and P62 were also observed in normal human proliferative, secretory, and decidua tissues. In conclusion, endometrial autophagy may be essential for embryo implantation, and it may be associated with endometrial decidualization during early pregnancy. KEY MESSAGE • Autophagy-related markers were significantly decreased at implantation site. • Autophagy inhibition results in abnormal decidualization. • Autophagy is essential for embryo implantation.