The most commonly used locomotor strategy in rodents is left-right limb alternation. Mutation of the axon guidance molecule EphA4 profoundly alters this basic locomotor pattern to synchrony. Here we report that conditional mutation of EphA4 in spinal interneurons expressing the transcription factor Lbx1 degrades the robustness in the expression of left-right alternating gait during development. Lbx1 EphA4 conditional mice exhibit alternating gait when walking on ground, but synchronous gait in environments with decreased weight-load, like swimming and airstepping. Using cell-type-specific, transient pharmacogenetic silencing approaches, we attribute this behavioral gait switch to neuronal activity of dorsal Lbx1 spinal interneurons. We also found that in Lbx1 EphA4 conditional mice these dorsal interneurons form aberrant bilateral connections to motor neurons, thereby indirectly transmitting received unilateral proprioceptive sensory information to both spinal sides. Together, our findings reveal the behavioral and circuit-level impact of conditional EphA4 mutation in a transcriptionally defined spinal interneuron subpopulation.

Background: Atrial fibrillation (AF) is a growing healthcare burden, for which pulmonary vein isolation (PVI) using cryoballoon (CB) or radiofrequency (RF) represent attractive therapies. Women are at higher risk of recurrence after AF ablation and present a specific complications profile. Therefore, a systematic catheter‐specific assessment of pulmonary vein isolation is urgently needed in women. Objective: Systematically assessing the sex‐specific efficacy/safety of CB vs RF ablation. Methods: We performed a structured database search of the scientific literature for randomized controlled trials (RCTs) and observational prospective studies (OPS) comparing CB and RF ablation efficacy at 1 year. We investigated the reporting of sex‐specific analyses and assessed the comparative sex‐specific efficacy, safety and procedural characteristics of CB vs RF using random‐effect meta‐regression accounting for the proportion of enrolled women. Results: Twenty‐three studies were included (18 OPS and 5 RCTs) for a total of 13 509 patients. Sex‐specific outcomes by ablation device were reported in two and sex‐specific regression in four studies, none of which took the ablation device into account. Meta‐regression accounting for the proportion of enrolled women showed no significant difference in outcomes between RF or CB. Conclusion: The sex‐specific reporting in trials comparing CB to RF is extremely low. A quantitative meta‐regression using the percentage of enrolled women as sex‐specific indicator did not show any difference between CB and RF but acknowledging the low percentage of enrolled women and the lack of sex‐specific data, further research including patient‐level data is urgently needed to draw more definitive conclusions.

No abstract