IL-1 receptor-activated kinase 1 (IRAK1) is involved in signal transduction downstream of many TLRs and the IL-1R. Its potential as a drug target for chronic inflammatory diseases is underappreciated. To study its functional role in joint inflammation, we generated a mouse model expressing a functionally inactive IRAK1 (IRAK1 kinase deficient, IRAK1KD), which also displayed reduced IRAK1 protein expression and cell type–specific deficiencies of TLR signaling. The serum transfer model of arthritis revealed a potentially novel role of IRAK1 for disease development and neutrophil chemoattraction exclusively via its activity in nonhematopoietic cells. Consistently, IRAK1KD synovial fibroblasts showed reduced secretion of neutrophil chemoattractant chemokines following stimulation with IL-1β or human synovial fluids from patients with rheumatoid arthritis (RA) and gout. Together with patients with RA showing prominent IRAK1 expression in fibroblasts of the synovial lining, these data suggest that targeting IRAK1 may be therapeutically beneficial. As pharmacological inhibition of IRAK1 kinase activity had only mild effects on synovial fibroblasts from mice and patients with RA, targeted degradation of IRAK1 may be the preferred pharmacologic modality. Collectively, these data position IRAK1 as a central regulator of the IL-1β–dependent local inflammatory milieu of the joints and a potential therapeutic target for inflammatory arthritis.

Objective: To determine the effect of an innovative, online-based intervention, addressing the possible decline of physical activity (PA) and increase of sedentary behavior (SB) during COVID-19 stay at home restrictions in Switzerland.Methods: This study investigated the effect of a two-week, social cognitive theory based, online-video moderate to vigorous (MV)PA or SB intervention on MVPA and SB behaviour and intention via a 3 group by 2 time point parallel randomized controlled trial during the COVID-19 pandemic. Adults (≥18 yo) were recruited over the internet between April 10th and April 19th 2020 (n = 129; 75.2% female; mean age = 29.0 [SD 11.8] years). Both intervention groups received five videos targeting either SB for the SB group or MVPA for the MVPA group and were compared to an attention control group (fruit and vegetable consumption). It was hypothesized that MVPA time and intention would increase for the MVPA group and the SB group would outperform control on SB behaviour and intention indicators.Results: No significant interactions were found for the MVPA group (n = 41) versus control (n = 40). Only one significant interaction was measured for the SB group (n = 48; intention of active breaks F = (2,114) = 5.84, p = 0.004, ηp2 = 0.09). Although mostly non-significant and small effects, the MVPA group showed results pointing in the hypothesized direction on all PA indicators and the SB on all SB indicators, respectively.Conclusion: Considering this study’s limitations (e.g. small intervention dose), video-based online PA and SB interventions seem promising and feasible. This approach is appropriate for COVID-19 and other stay at home situations.

Introduction In complex sensorimotor behavior, uncertainty arises from ambiguity in the sensory inputs of the environment (e.g. Kersten et al., 2004) as well as from noise in sensory detection and motor execution (e.g. Todorov & Jordan, 2002). Moreover, the observable sensory inputs are delayed and there are typically multiple solutions to solve a motor task (e.g. Franklin & Wolpert, 2011). In sports, where human capacity reaches its limit with these challenges, dealing with uncertainty is crucial. Thus, the question arises how humans are able to deal with uncertainty in sensorimotor control in naturalistic situations such as sports. Methods A systematic search for original articles was conducted in six scientific databases with the following terms: (uncertainty OR noise) AND (sensor* OR motor) AND control AND sport AND movement. After independently screening 4,309 articles and additional reference lists by two raters, 70 articles remained for the review. Results There is clear evidence that prior knowledge (or similar contextual information) and multiple sensory information affect perception, action and performance. Moreover, there is considerable evidence that prior knowledge and multiple sensory information get integrated according to their reliability in order to reduce uncertainty. Furthermore, it has been reported that gaze behavior is close to the optimal compared to an optimal Bayesian observer in an expected and unexpected uncertain environment. There is also considerable evidence that not all variables have to be controlled and rather uncertainty is accepted in variables that do not impair overall performance. Some findings show that inherent noise is taken into account when planning motor execution so that the potential costs and rewards of the movement outcome are optimized. Finally, some findings show that unforeseen perturbation can be absorbed by means of higher muscle stiffness resulting from muscular co-contraction. Discussion The strategies to deal with uncertainty mentioned in the results section can be summarized under the umbrella of Bayesian decision theory (Franklin & Wolpert, 2011). Only a few alternative models were referenced that, however, were conceptually quite similar to Bayesian models. Therefore, Bayesian decision theory seems to offer a promising framework for future research on uncertainty in sensorimotor control in sport science. References Franklin, D. W., & Wolpert, D. M. (2011). Computational mechanisms of sensorimotor control. Neuron, 72(3), 425-442. https://doi.org/10.1016/j.neuron.2011.10.006 Kersten, D., Mamassian, P., & Yuille, A. (2004). Object perception as Bayesian inference. Annual Review of Psychology, 55, 271-304. https://doi.org/10.1146/annurev.psych.55.090902.142005 Todorov, E., & Jordan, M. I. (2002). Optimal feedback control as a theory of motor coordination. Nature Neuroscience, 5(11), 1226-1235. https://doi.org/10.1038/nn963