Disturbed brain energy metabolism in a rodent model of DYT-TOR1A dystonia.

DYT-TOR1A (DYT1) dystonia, characterized by reduced penetrance and suspected environmental triggers, is explored using a "second hit" DYT-TOR1A rat model. We aim to investigate the biological mechanisms driving the conversion into a dystonic phenotype, focusing on the striatum's role in dystonia pathophysiology. Sciatic nerve crush injury was induced in ∆ETorA rats, lacking spontaneous motor abnormalities, and wild-type (wt) rats. Twelve weeks post-injury, unbiased RNA-sequencing was performed on the striatum to identify differentially expressed genes (DEGs) and pathways. Fenofibrate, a PPARα agonist, was introduced to assess its effects on gene expression. 18F-FDG autoradiography explored metabolic alterations in brain networks. Low transcriptomic variability existed between naïve wt and ∆ETorA rats (17 DEGs). Sciatic nerve injury significantly impacted ∆ETorA rats (1009 DEGs) compared to wt rats (216 DEGs). Pathway analyses revealed disruptions in energy metabolism, specifically in fatty acid ß-oxidation and glucose metabolism. Fenofibrate induced gene expression changes in wt rats but failed in ∆ETorA rats. Fenofibrate increased dystonia-like movements in wt rats but reduced them in ∆ETorA rats. 18F-FDG autoradiography indicated modified glucose metabolism in motor and somatosensory cortices and striatum in both ∆ETorA and wt rats post-injury. Our findings highlight perturbed energy metabolism pathways in DYT-TOR1A dystonia, emphasizing compromised PPARα agonist efficacy in the striatum. Furthermore, we identify impaired glucose metabolism in the brain network, suggesting a potential shift in energy substrate utilization in dystonic DYT-TOR1A rats. These results contribute to understanding the pathophysiology and potential therapeutic targets for DYT-TOR1A dystonia.

Does an instructional video as a stand-alone tool promote the acquisition of practical clinical skills? A randomised simulation research trial of skills acquisition and short-term retention.

BACKGROUND: The effectiveness of instructional videos as a stand-alone tool for the acquisition of practical skills is yet unknown because instructional videos are usually didactically embedded. Therefore, we evaluated the acquisition of the skill of a humeral intraosseous access via video in comparison to that of a self-study with an additional retention test. METHODS: After ethical approval, we conducted two consecutive studies. Both were designed as randomised controlled two-armed trials with last-year medical students as independent samples at our institutional simulation centre of a tertiary university hospital centre. In Study 1, we randomly assigned 78 participants to two groups: Vid-Self participants watched an instructional video as an intervention, followed by a test, and after seven days did a self-study as a control, followed by a test. Self-Vid ran through the trial in reverse order. In Study 2, we investigated the influence of the sequence of the two teaching methods on learning success in a new sample of 60 participants: Vid-Self watched an instructional video and directly afterward did the self-study followed by a test, whereas Self-Vid ran through that trial in reverse order. In Studies 1 and 2, the primary outcome was the score (worst score = 0, best score = 20) of the test after intervention and control. The secondary outcome in Study 1 was the change in score after seven days. RESULTS: Study 1: The Vid-Self (Participants n = 42) was superior to the Self-Vid (n = 36) (mean score 14.8 vs. 7.7, p < 0.001). After seven days, Self-vid outperformed Vid-Self (mean score 15.9 vs. 12.5, p < 0.001). Study 2: The Vid-Self (n = 30) and Self-Vid (n = 30) scores did not significantly differ (mean 16.5 vs. mean 16.5, p = 0.97). CONCLUSION: An instructional video as a stand-alone tool effectively promotes the acquisition of practical skills. The best results are yielded by a combination of an instructional video and self-study right after each other, irrespective of sequence. TRIAL REGISTRATIONS: ClinicalTrials.gov: NCT05066204 (13/04/2021) (Study 1) and NCT04842357 (04/10/2021) (Study 2).

Light-sensitive short hypocotyl genes confer symbiotic nodule identity in the legume Medicago truncatula.

Legumes produce specialized root nodules that are distinct from lateral roots in morphology and function, with nodules intracellularly hosting nitrogen-fixing bacteria. We have previously shown that a lateral root program underpins nodule initiation, but there must be additional developmental regulators that confer nodule identity. Here, we show two members of the LIGHT-SENSITIVE SHORT HYPOCOTYL (LSH) transcription factor family, predominantly known to define shoot meristem complexity and organ boundaries, function as regulators of nodule organ identity. In parallel to the root initiation program, LSH1/LSH2 recruit a program into the root cortex that mediates the divergence into nodules, in particular with cell divisions in the mid-cortex. This includes regulation of auxin and cytokinin, promotion of NODULE ROOT1/2 and Nuclear Factor YA1, and suppression of the lateral root program. A principal outcome of LSH1/LSH2 function is the production of cells able to accommodate nitrogen-fixing bacteria, a key feature unique to nodules.

Guidelines for naming and studying plasma membrane domains in plants.

Biological membranes play a crucial role in actively hosting, modulating and coordinating a wide range of molecular events essential for cellular function. Membranes are organized into diverse domains giving rise to dynamic molecular patchworks. However, the very definition of membrane domains has been the subject of continuous debate. For example, in the plant field, membrane domains are often referred to as nanodomains, nanoclusters, microdomains, lipid rafts, membrane rafts, signalling platforms, foci or liquid-ordered membranes without any clear rationale. In the context of plant-microbe interactions, microdomains have sometimes been used to refer to the large area at the plant-microbe interface. Some of these terms have partially overlapping meanings at best, but they are often used interchangeably in the literature. This situation generates much confusion and limits conceptual progress. There is thus an urgent need for us as a scientific community to resolve these semantic and conceptual controversies by defining an unambiguous nomenclature of membrane domains. In this Review, experts in the field get together to provide explicit definitions of plasma membrane domains in plant systems and experimental guidelines for their study. We propose that plasma membrane domains should not be considered on the basis of their size alone but rather according to the biological system being considered, such as the local membrane environment or the entire cell.

Exchange of a Tracheal Tube and Supraglottic Airway Device: Evaluation of Different Techniques in Three Simulated Airway Scenarios (TUBE Study)-A Prospective, Randomised Controlled Study.

BACKGROUND: The swapping of a supraglottic airway device or a tracheal tube in anaesthetised adult patients is a challenging procedure because potential complications through hypoxemia and loss of airway may occur, with life-threatening implications. This study aims to evaluate which airway technique offers the highest success rate concerning a secure airway in established supraglottic airway and tracheal tube airway exchange scenarios. METHODS: After ethical approval, anaesthesiologists were randomised 1:1 into simulated scenarios: an LTS group (malpositioned laryngeal tube) and a Cuff group (relevant cuff leakage of a placed tracheal tube). After that, both groups completed a common scenario consisting of a partially obstructed tracheal tube lumen in a fixed prone position with a Mayfield clamp. The primary endpoint was a successful tracheal airway exchange within ten minutes after the start of the scenario and before severe hypoxemia (SpO2 < 80%) arose. Secondary endpoints were the evaluation of factors influencing success after 10 min. RESULTS: In total, 60 anaesthesiologists (LTS group n = 30; Cuff group n = 30) with a median experience of 7 years (IQR 4-11) were observed. Within 10 min, a malpositioned laryngeal tube was successfully exchanged by 27/30 (90%) participants, compared to the exchange of a tracheal tube with a relevant cuff leakage by 29/30 (97%; p > 0.05). An airway exchange in an obstructed tube scenario occurred in 22/59 (37%). Loss of airway maintenance showed an obvious association with failure in the common scenario (p = 0.02). CONCLUSION: The results of this simulation-based study reflect that the exchange of an existing but insufficient airway device in clinical practice is a high-risk procedure. Especially in a fixed prone position, the deliberate evaluation of the existing airway patency and well-conceived airway management in the case of the accidental loss of the airway or obstructed airway access are crucial.