A better understanding of the negative impact of general anesthetics on gastrointestinal motility requires thorough knowledge of their molecular targets. In this respect the muscarinic cationic current (mICAT carried mainly via TRPC4 channels) that initiates cholinergic excitation-contraction coupling in the gut is of special interest. Here we aimed to characterize the effects of one of the most commonly used “dissociative anesthetics”, ketamine, on mICAT. Patch-clamp and tensiometry techniques were used to investigate the mechanisms of the inhibitory effects of ketamine on mICAT in single mouse ileal myocytes, as well as on intestinal motility. Ketamine (100 µM) strongly inhibited both carbachol- and GTPγS-induced mICAT. The inhibition was slow (time constant of about 1 min) and practically irreversible. It was associated with altered voltage dependence and kinetics of mICAT. In functional tests, ketamine suppressed both spontaneous and carbachol-induced contractions of small intestine. Importantly, inhibited by ketamine mICAT could be restored by direct TRPC4 agonist (-)-englerin A. We identified mICAT as a novel target for ketamine. Signal transduction leading to TRPC4 channel opening is disrupted by ketamine mainly downstream of muscarinic receptor activation, but does not involve TRPC4 per se. Direct TRPC4 agonists may be used for the correction of gastrointestinal disorders provoked by general anesthesia.

ImportanceThe conflict in Ukraine has forced civilian hospitals with limited trauma and battlefield medicine experience to care for casualties of war, placing significant strain on the health care system. Using the Checklist for Early Recognition and Treatment of Acute Illness and Injury (CERTAIN) program, a multimodal trauma critical care knowledge-exchange platform was created for clinicians practicing in these institutions.ObjectivesTo describe the development and implementation of the CERTAIN for Ukraine program and to evaluate the reach of this intervention, together with participant engagement and satisfaction.Design, Setting, and ParticipantsThis quality improvement study included clinicians caring for critically ill patients during the ongoing Ukrainian conflict who were part of a community developed using a messaging app. The program was implemented by a group of international trauma and critical care experts in collaboration with critical care leaders from the Shupyk National Healthcare University in Kyiv, Ukraine. This study evaluates data collected from the CERTAIN for Ukraine program from its launch on April 9, 2022, to August 31, 2022.InterventionsThe initiative comprised a longitudinal series of interactive tele-education sessions, a webpage containing the CERTAIN approach and current trauma critical care guidelines translated into Ukrainian and Russian, and a private messaging chat for asynchronous discussion.Main Outcomes and MeasuresParticipant engagement and satisfaction were tracked using multimedia analytics and a post-session survey.ResultsSince program launch, 838 participants have joined the messaging group, and 6 tele-education sessions have been delivered, with 1835 total views. The CERTAIN website has had 3527 visits, mainly from Ukraine (1378 [39%]) and the United States (1060 [30%]). Of the 74 completed postsession surveys, 65 respondents (88%) rated the course content excellent or very good, and 73 (99%) recommended it to others.Conclusions and RelevanceThe findings of this quality improvement study indicate that, using widely available and low-cost platforms, knowledge was shared rapidly and efficiently to a large community of clinicians practicing in a wartime environment with broad-based engagement and a high level of learner satisfaction.

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The aim: To investigate the effectiveness of usage of the free radical scavenger Edaravone in the therapy of women with AIS. Materials and methods: A prospective study was conducted of 48 women with AIS, divided into two groups. Patients in the first group (n = 36) were treated with edaravone 30 mg twice a day intravenously. Neuroprotectors were not used in the control group (n = 12). Clinical-instrumental and neurological examination (Glasgow scale (SCG), FOUR, NIHSS, and neuronspecific enolase (NSE) levels) were performed on all patients. Results: The mean FOUR score in the 1th group increased from 11.04±0.85 to 15.47±0.63 points against 11.39±0.56 to 13.46±1.49 in the control group (p<0.05). The level of NSE in control group patients increased 10-fold (from 9.2 to 96.4 ng/ml, p<0.01). Subsequently, there was a rapid decrease in NSE level in 1th group, and in the control group until 10 days of treatment, the level of NSE did not reach the reference values (p <0.05). Conclusions: The introduction of edaravone in women with AIS results in positive results already in the acute period of the disease. The use of edaravon was significantly effective on the FOUR scale and the dynamics of NSE levels.

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