Cytochrome P450 3A4 activity and genetic variants as predictors of liver failure in patients with obstructive jaundice.

Liver failure in patients with obstructive jaundice is a significant contributor to mortality within this patient cohort. The exact mechanism and triggers of this occurrence are yet to be fully understood. With this in mind, our study aimed to assess the correlation between the urinary 6 ß-OHC/C ratio and various biochemical parameters of liver function. Furthermore, we conducted genotyping of CYP3A4*22 (rs35599367), CYP3A5*3 (rs776746) polymorphic markers to investigate the potential effects of their variants on the probability of liver failure in obstructive jaundice. Our study included 75 patients diagnosed with severe obstructive jaundice. All test subjects underwent functional liver tests, and control blood tests were administered on the seventh day following biliary decompression. Patients were categorized into two groups: group 1 - patients without liver failure (n = 60) and group 2 - patients with liver failure (n = 15). Laboratory indexes such as 6 ß -OHC concentration and 6 ß- OHC/cortisol ratio can serve as significant predictors of liver failure in patients with moderate and severe degree obstructive jaundice after biliary decompression. Based on the study of "wild" and polymorphic variants of CYP3A4*22 (CC and CT) and polymorphism of CYP3A5*3A6986G (GG, GA, AA), it was discovered that liver failure in the CYP3A4*22 variant may be associated with the CC genotype, and in the CYP3A5*3 variant - with the GA genotype. Hence, the determination of 6ß- OHC concentration and 6ß- OHC/C ratio, as well as the analysis of polymorphic and "wild" variants of CYP3A4*22 (CC and CT) and CYP3A5*3 polymorphism A6986G (GG, GA, AA), may play a crucial role in predicting liver failure in patients with obstructive jaundice.

Clinical, Morphological Justification and First Experience in the Use of Radiofrequency as Well as Microwave Ablation Treatment Methods of Liver Echinococcosis.

Background: The current study considers a new direction of surgical treatment of liver echinococcosis - the use of minimally invasive treatment methods of parasitic cysts. Methods: After clinical and morphological substantiation of the very possibility of carrying out such procedures, 9 microwave ablations (MWA) and 3 radiofrequency ablations (RFA) of cysts were performed in patients with liver echinococcosis from 2017 to 2021 in the surgical clinic of Botkin Hospital, Moscow, Russia. A comparative analysis of treatment results of patients with echinococcal liver cysts (12 patients who underwent "percutaneous puncture, aspiration, injection and reaspiration" (PAIR) procedure and 12 patients - MWA and RFA) was carried out. Results: The number of complications according to Clavien-Dindo classification was as follows: 8 after PAIR procedure, 3 after RFA and 3 after MWA. The median hospital length of stay (LOS) after PAIR procedure was 6.46 days versus 4.7 and 4 in the groups of patients who underwent RF and MW ablation, respectively. The frequency of relapses within the first year after PAIR procedure was 25%. The patients who underwent ablation procedures had no relapses of liver echinococcosis during observation. Conclusion: The presented clinical and morphological substantiation and the experience of using various types of ablation techniques on echinococcal cysts, as well as a comparative analysis with a commonly used PAIR treatment method, demonstrated the safety of RFA and MWA for the patient and efficacy in relation to the hydatid process.

Open Ephys: an open-source, plugin-based platform for multichannel electrophysiology.

OBJECTIVE: Closed-loop experiments, in which causal interventions are conditioned on the state of the system under investigation, have become increasingly common in neuroscience. Such experiments can have a high degree of explanatory power, but they require a precise implementation that can be difficult to replicate across laboratories. We sought to overcome this limitation by building open-source software that makes it easier to develop and share algorithms for closed-loop control. APPROACH: We created the Open Ephys GUI, an open-source platform for multichannel electrophysiology experiments. In addition to the standard 'open-loop' visualization and recording functionality, the GUI also includes modules for delivering feedback in response to events detected in the incoming data stream. Importantly, these modules can be built and shared as plugins, which makes it possible for users to extend the functionality of the GUI through a simple API, without having to understand the inner workings of the entire application. MAIN RESULTS: In combination with low-cost, open-source hardware for amplifying and digitizing neural signals, the GUI has been used for closed-loop experiments that perturb the hippocampal theta rhythm in a phase-specific manner. SIGNIFICANCE: The Open Ephys GUI is the first widely used application for multichannel electrophysiology that leverages a plugin-based workflow. We hope that it will lower the barrier to entry for electrophysiologists who wish to incorporate real-time feedback into their research.