Key points The endothelium plays a pivotal role in the vascular response to chemical and mechanical stimuli.The endothelium is exquisitely sensitive to ACh, although the physiological significance of ACh‐induced activation of the endothelium is unknown.In the present study, we investigated the mechanisms of flow‐mediated endothelial calcium signalling.Our data establish that flow‐mediated endothelial calcium responses arise from the autocrine action of non‐neuronal ACh released by the endothelium. AbstractCirculating blood generates frictional forces (shear stress) on the walls of blood vessels. These frictional forces critically regulate vascular function. The endothelium senses these frictional forces and, in response, releases various vasodilators that relax smooth muscle cells in a process termed flow‐mediated dilatation. Although some elements of the signalling mechanisms have been identified, precisely how flow is sensed and transduced to cause the release of relaxing factors is poorly understood. By imaging signalling in large areas of the endothelium of intact arteries, we show that the endothelium responds to flow by releasing ACh. Once liberated, ACh acts to trigger calcium release from the internal store in endothelial cells, nitric oxide production and artery relaxation. Flow‐activated release of ACh from the endothelium is non‐vesicular and occurs via organic cation transporters. ACh is generated following mitochondrial production of acetylCoA. Thus, we show ACh is an autocrine signalling molecule released from endothelial cells, and identify a new role for the classical neurotransmitter in endothelial mechanotransduction.

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This multi-method study provides detailed information about the friendships of 87 children with ADHD (77.0% boys) and 46 comparison children (73.9% boys) between the ages of 7 and 13.The methods used in the study included parent and teacher ratings, self-report measures, and direct observation of friends' dyadic behaviours in three structured analogue tasks. Results indicated that, in contrast with comparison children, children with ADHD had friends with high levels of ADHD and oppositional symptoms; they perceived fewer positive features and more negative features, and were less satisfied in their friendships. Observational data indicated that children with ADHD performed both more legal and more illegal manoeuvres than comparison children in a fast-paced competitive game. While negotiating with their friends, children with ADHD made more insensitive and self-centred proposals than comparison children. In dyads consisting of one child with ADHD and one typically developing child, children with ADHD were often more controlling than their non-diagnosed friends. Globally, these results were robust and did not seem to be affected by age differences, ADHD subtypes, comorbidities, and medication status. Given the increased recognition of ADHD in adolescence and adulthood as well as the fact that negative peer reputation in childhood very strongly predicts mental-health status by early adulthood, this research may lead to the discovery of meaningful ways to help people with ADHD achieve improved mental health and happiness over their lifespan.Friendship Interactions of Children with ADHD 1

Background Location-based augmented reality (AR) games, such as Pokémon GO and Harry Potter: Wizards Unite, have been shown to have a beneficial impact on the physical activity, social connectedness, and mental health of their players. In March 2020, global social distancing measures related to the COVID-19 pandemic prompted the AR games developer Niantic Inc to implement several changes to ensure continued player engagement with Pokémon GO and Harry Potter: Wizards Unite. We sought to examine how the physical and mental well-being of players of these games were affected during the unprecedented COVID-19 restriction period as well as how their video game engagement was affected. Objective The aims of this study were to examine the impact of COVID-19–related social restrictions on the physical and mental well-being of AR game players; to examine the impact of COVID-19–related social restrictions on the use of video games and motivations for their use; and to explore the potential role of AR games (and video games in general) in supporting well-being during COVID-19–related social restrictions. Methods A mixed methods web-based self-reported survey was conducted in May 2020, during which COVID-19–related social restrictions were enforced in many countries. Participants were recruited on the web via four subreddits dedicated to Pokémon GO or Harry Potter: Wizards Unite. Data collected included quantitative data on demographics, time spent playing video games, physical activity, and mental health; qualitative data included motivations to play and the impact of video games on mental health during COVID-19 lockdown. Results We report results for 2004 participants (1153/1960 male, 58.8%, average age 30.5 years). Self-reported physical activity during COVID-19–related social restrictions significantly decreased from 7.50 hours per week on average (SD 11.12) to 6.50 hours (SD 7.81) (P<.001). More than half of the participants reported poor mental health (925/1766, 52.4%; raw World Health Organization–5 Well-Being Index score <13). Female gender, younger age, and reduced exercise were significant predictors of poor mental health. Participants reported a significant increase in video game play time from 16.38 hours per week on average (SD 19.12) to 20.82 hours (SD 17.49) (P<.001). Approximately three quarters of the participants (n=1102/1427, 77.2%) reported that playing video games had been beneficial to their mental health. The changes made to Pokémon GO and Harry Potter: Wizards Unite were very well received by players, and the players continued to use these games while exercising and to maintain social connection. In addition to seeking an escape during the pandemic and as a form of entertainment, participants reported that they used video games for emotional coping and to lower stress, relax, and alleviate mental health conditions. Conclusions AR games have the potential to promote physical and mental health during the COVID-19 pandemic. Used by populations under isolation and distress, these games can improve physical and mental health by providing virtual socialization, sustained exercise, temporal routine, and mental structure. Further research is needed to explore the potential of AR games as digital behavioral interventions to maintain human well-being in the wider population.

We examined how the real-life dyadic friendships of 87 children with ADHD and 46 comparison children (76 % boys) aged 7-13 years evolved during a 6-month follow-up period. The methods included friendship quality self-report measures and direct observation of friends' dyadic behaviors in three structured analogue tasks. At Time 2, the friends of the participants with ADHD reported less positive friendship quality and more conflict with their friends than at Time 1. They were also considerably less satisfied with their friendship than 6 months prior. In contrast, the friends of comparison children reported fewer negative friendship features, more positive friendship features and a slightly greater friendship satisfaction than at Time 1. In sharp contrast with the invited friends' reports, referred children with ADHD did not report deterioration in their friendship quality over time. Unlike comparison children who significantly reduced violations of game rules between Time 1 and Time 2, children with ADHD broke more game rules during the same period. In negotiating with friends, comparison children, but not children with ADHD, reduced the number of self-centered and insensitive proposals at Time 2. Controlling for Time 1 variance, violations of game rules and a self-centered, insensitive negotiation approach predicted deterioration in friendship quality for children with and without ADHD over time.