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Aims Understanding contexts in which social harms from drinking occur can help develop context-based harm reduction efforts. However, there is little knowledge of specific drinking contexts where such harms occur and whether these are gender or age specific. We aimed to investigate associations of a range of drinking contexts and social harms from drinking among young adults at age 30. Methods We used data from 2187 30-year-old adults. Latent constructs of gender-specific drinking contexts were created using factor analysis. We performed multivariate logistic regression between drinking contexts and a range of social harms from drinking, separately by gender. Results After accounting for social roles and binge drinking, gender-specific solitary drinking contexts ('home drinking' for men and 'daytime drinking' for women) were positively associated with marital problems and problems with other family members and friends. Conversely, 'social drinking' was not. Work-related drinking among men was associated with marital/intimate relationship problems and friendship problems. After accounting for mental health symptoms, women's home drinking was associated with marital problems. Conclusion We found that experiences of social harms from drinking at 30 years differ depending on the drinker's gender and context. Our findings suggest that risky contexts and associated harms are still significant among 30-year-old adults, indicating that a range of gender-specific drinking contexts should be represented in harm reduction campaigns. The current findings also highlight the need to consider gender to inform context-based harm reduction measures and to widen the age target for these beyond emerging adults. [ABSTRACT FROM AUTHOR]

Human group IIA-secreted phospholipase A2 (sPLA2-IIA) is an important regulator of cytokine-mediated inflammatory responses in both in vitro and in vivo models of rheumatoid arthritis (RA). However, treatment of RA patients with sPLA2-IIA inhibitors shows only transient benefit. Using an activity-impaired sPLA2-IIA mutant protein (H48Q), we show that up-regulation of TNF-dependent PGE2 production and cyclooxygenase-2 (COX-2) induction by exogenous sPLA2-IIA in RA fibroblast-like synoviocytes (FLSs) is independent of its enzyme function. Selective cytosolic phospholipase A2-α (cPLA2-α) inhibitors abrogate TNF/sPLA2-IIA-mediated PGE2 production without affecting COX-2 levels, indicating arachidonic acid (AA) flux to COX-2 occurs exclusively through TNF-mediated activation of cPLA2-α. Nonetheless, exogenous sPLA2-IIA, but not H48Q, stimulates both AA mobilization from FLSs and microparticle-derived AA release that is not used for COX-2-dependent PGE2 production. sPLA2-IIA-mediated AA production is inhibited by pharmacological blockade of sPLA2-IIA but not cPLA2-α. Exogenous H48Q alone, like sPLA2-IIA, increases COX-2 protein levels without inducing PGE2 production. Unlike TNF, sPLA2-IIA alone does not rapidly mobilize NF-κB or activate phosphorylation of p38 MAPK, two key regulators of COX-2 protein expression, but does activate the ERK1/2 pathway. Thus, sPLA2-IIA regulates AA flux through the cPLA2-α/COX-2 pathway in RA FLSs by up-regulating steady state levels of these biosynthetic enzymes through an indirect mechanism, rather than direct provision of substrate to the pathway. Inhibitors that have been optimized for their potency in enzyme activity inhibition alone may not adequately block the activity-independent function of sPLA2-IIA. [ABSTRACT FROM AUTHOR]

Background: Alcohol and other drug (AOD) use patterns have altered as a result of the coronavirus (COVID-19) pandemic restrictions. This study aimed to: (i) determine the impact of the pandemic on patterns of AOD use among individuals seeking treatment, (ii) identify which mental health and resilience factors were associated with changes in patterns of AOD use and (iii) evaluate changes in the contextual factors (eg, motivations) associated with use., Methods: Cross-sectional surveys were completed by clients (n = 325) who had sought AOD treatment from January 2020 onwards. We measured quantity and frequency of AOD use now compared to before the pandemic, mental health (depression, anxiety, trauma exposure), resilience and contextual factors related to AOD use., Results: Quantity of tobacco and cannabis use increased post-pandemic, while methamphetamine and alcohol did not change. Depression was associated with more frequent alcohol use now compared to before the pandemic, while anxiety and lower resilience were associated with less frequent cannabis use now. Lower resilience was associated changes in methamphetamine use. Depression was associated with using more frequently for enjoyment and to alleviate loneliness following the pandemic, and anxiety was associated with using earlier in the day and to alleviate boredom., Conclusions: The pandemic has led to increased frequency of AOD use for a subset of individuals seeking treatment. Depression, anxiety and resilience are important factors associated with altered AOD use, and changes in the motivations and control surrounding use. Special consideration of this should be considered during AOD treatment through the pandemic., Competing Interests: Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2021.)