Dickersonaggerholm9313

2%). A total of 80.2% of patients were discharged on antiplatelet therapy alone. Peridevice flow was less then 3 mm in 98.4% at follow-up TOE. Device-related thrombus (DRT) was seen in 1.6% of cases. Cardiovascular death or ischaemic stroke occurred in 8.7% of patients at 2 years. The ischaemic stroke rate was 2.2%/year-a 67% reduction compared to the CHA2DS2-VASc predicted rate. Major bleeding (Bleeding Academic Research Consortium type ≥ 3) occurred at rates of 10.1%/year (year 1) and 4.0%/year (year 2). CONCLUSION Following LAAO with the Amplatzer Amulet device, the ischaemic stroke rate was reduced by 67% compared to the predicted risk. Closure was complete in 98.4% of cases and DRT seen in only 1.6%. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email journals.permissions@oup.com.Dietary change is needed to improve health and reduce the environmental burden of food production and consumption. Using an Intervention Mapping approach, this study aimed to explore the views caterers and customers held towards point-of-choice interventions that promote healthy and environmentally friendly (EF) food and beverage choices at the University of Sheffield. Intervention options proposed during focus groups were devised using the Nuffield Bioethics ladder of intervention. Ten focus groups were held involving caterers (n = 16) and customers (n = 45). Thematic analysis was conducted on the transcripts of caterer and customer focus groups seperately, and then comparisons were made to identify concerns about the acceptability and feasibility of intervention options. Attitudes towards intervention options varied considerably amongst stakeholders, with the greatest disparity of opinion in the acceptability of interventions that restrict or limit personal choice, particularly with regards to meat consumption. Information provision was favoured as an acceptable intervention by both customers and caterers. However, labelling products in terms of their environmental impact was considered practically unfeasible. Social norms around eating also emerged as influencing the acceptability and feasibility of interventions with concerns raised about shaming customers who chose meat, the exclusivity of vegan choices and the limited availability and appeal of meatless café options. Financial considerations were the main priority of caterers when discussing point-of-choice interventions. An acceptable and feasible café-based intervention ought to increase awareness and understanding of healthy and EF food choices, protect customer choice and avoid additional costs. © The Author(s) 2020. check details Published by Oxford University Press. All rights reserved. For permissions, please email journals.permissions@oup.com.In several types of central mammalian synapses, sustained presynaptic stimulation leads to a sequence of two components of synaptic vesicle release, reflecting the consecutive contributions of a fast-releasing pool (FRP) and of a slow-releasing pool (SRP). Previous work has shown that following common depletion by a strong stimulation, FRP and SRP recover with different kinetics. However, it has remained unclear whether any manipulation could lead to a selective enhancement of either FRP or SRP. To address this question, we have performed local presynaptic calcium uncaging in single presynaptic varicosities of cerebellar interneurons. These varicosities typically form "simple synapses" onto postsynaptic interneurons, involving several (one to six) docking/release sites within a single active zone. We find that strong uncaging laser pulses elicit two phases of release with time constants of ∼1 ms (FRP release) and ∼20 ms (SRP release). When uncaging was preceded by action potential-evoked vesicular release, the extent of SRP release was specifically enhanced. We interpret this effect as reflecting an increased likelihood of two-step release (docking then release) following the elimination of docked synaptic vesicles by action potential-evoked release. In contrast, a subthreshold laser-evoked calcium elevation in the presynaptic varicosity resulted in an enhancement of the FRP release. We interpret this latter effect as reflecting an increased probability of occupancy of docking sites following subthreshold calcium increase. In conclusion, both fast and slow components of release can be specifically enhanced by certain presynaptic manipulations. Our results have implications for the mechanism of docking site replenishment and the regulation of synaptic responses, in particular following activation of ionotropic presynaptic receptors. © 2020 Blanchard et al.Mice lacking functional large-conductance voltage- and Ca2+-activated K+ channels (BK channels) are viable but have motor deficits including ataxia and weakness. The cause of weakness is unknown. In this study, we discovered, in vivo, that skeletal muscle in mice lacking BK channels (BK-/-) was weak in response to nerve stimulation but not to direct muscle stimulation, suggesting a failure of neuromuscular transmission. Voltage-clamp studies of the BK-/- neuromuscular junction (NMJ) revealed a reduction in evoked endplate current amplitude and the frequency of spontaneous vesicle release compared with WT littermates. Responses to 50-Hz stimulation indicated a reduced probability of vesicle release in BK-/- mice, suggestive of lower presynaptic Ca2+ entry. Pharmacological block of BK channels in WT NMJs did not affect NMJ function, surprisingly suggesting that the reduced vesicle release in BK-/- NMJs was not due to loss of BK channel-mediated K+ current. Possible explanations for our data include an effect of BK channels on development of the NMJ, a role for BK channels in regulating presynaptic Ca2+ current or the effectiveness of Ca2+ in triggering release. Consistent with reduced Ca2+ entry or effectiveness of Ca2+ in triggering release, use of 3,4-diaminopyridine to widen action potentials normalized evoked release in BK-/- mice to WT levels. Intraperitoneal application of 3,4-diaminopyridine fully restored in vivo nerve-stimulated muscle force in BK-/- mice. Our work demonstrates that mice lacking BK channels have weakness due to a defect in vesicle release at the NMJ. © 2020 Wang et al.