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Ventricular tachycardia (VT) may lead to syncope and sudden cardiac death. Implantable loop recorders (ILR) are recommended in the clinical work-up of patients with unexplained syncope. Our aim was to evaluate if echocardiographic parameters assessed prior to ILR implantation in patients with unexplained syncope may aid in identifying individuals with an increased risk of VT. The present study included 288 ambulatory patients (mean age 58 ± 19 years, 51% women) with syncope (90%) and presyncope (10%) who had an ILR implanted in the diagnostic workup. All patients underwent an echocardiographic examination prior to device implantation (median 3 months [IQR 1 to 6 months]). We examined incident VT, defined as a first-time episode of VT (> 30 s) or non-sustained VT ( less then 30 s) detected by the ILR. During median follow-up of 2.9 years [IQR 1.3 to 3.5 years] of continuous rhythm monitoring, 36 patients (13%) were diagnosed with incident VT (n = 25 non-sustained VT, n = 11 sustained VT). In unadjusted Cox proportional hazards models, left ventricular (LV) mass index (HR 1.04 per 1 g/m2 increase [1.00 to 1.08], P = 0.047), mean LV wall thickness (HR 1.36 per 1 mm increase [1.08 to 1.71], P = 0.009), and global longitudinal strain (HR 1.15 per 1% decrease [1.05 to 1.25], P = 0.002) were significantly associated with VT. After adjusting for age, sex, implantable loop recorder indication and known heart failure, the above-mentioned parameters remained significantly associated with incident VT. LV mass index, LV wall thickness, and GLS may aid in identifying patients with increased risk of incident VT among patients with syncope. Echocardiography may potentially help select patients who can benefit from ILR.The accurate description of protein binding sites is essential to the determination of similarity and the application of machine learning methods to relate the binding sites to observed functions. This work describes CAVIAR, a new open source tool for generating descriptors for binding sites, using protein structures in PDB and mmCIF format as well as trajectory frames from molecular dynamics simulations as input. The applicability of CAVIAR descriptors is showcased by computing machine learning predictions of binding site ligandability. The method can also automatically assign subcavities, even in the absence of a bound ligand. The defined subpockets mimic the empirical definitions used in medicinal chemistry projects. It is shown that the experimental binding affinity scales relatively well with the number of subcavities filled by the ligand, with compounds binding to more than three subcavities having nanomolar or better affinities to the target. The CAVIAR descriptors and methods can be used in any machine learning-based investigations of problems involving binding sites, from protein engineering to hit identification. The full software code is available on GitHub and a conda package is hosted on Anaconda cloud. The short-stitch technique for midline laparotomy closure has been shown to reduce hernia rates, but long stitches remain the standard of care and the effect of the short-stitch technique on short-term results is not well known. The aim of this study was to compare the two techniques, using an ultra-long-term absorbable elastic suture material. Following elective midline laparotomy, 425 patients in 9 centres were randomised to receive wound closure using the short-stitch (USP 2-0 single thread, n = 215) or long-stitch (USP 1 double loop, n = 210) technique with a poly-4-hydroxybutyrate-based suture material (Monomax ). https://www.selleckchem.com/products/u18666a.html Here, we report short-term surgical outcomes. At 30 (+10)days postoperatively, 3 (1.40%) of 215 patients in the short-stitch group and 10 (4.76%) of 210 patients in the long-stitch group had developed burst abdomen [OR 0.2830 (0.0768-1.0433), p = 0.0513]. Ruptured suture, seroma and hematoma and other wound healing disorders occurred in small numbers without differences between groups. In a planned Cox proportional hazard model for burst abdomen, the short-stitch group had a significantly lower risk [HR 0.1783 (0.0379-0.6617), p = 0.0115]. Although this trial revealed no significant difference in short-term results between the short-stitch and long-stitch techniques for closure of midline laparotomy, a trend towards a lower rate of burst abdomen in the short-stitch group suggests a possible advantage of the short-stitch technique. NCT01965249, registered October 18, 2013. NCT01965249, registered October 18, 2013.Dibasic acids (DBA) with benzene rings having substituents and connected by a sulfurcontaining bridge exhibited radioprotective effectiveness when administered in non-toxic concentrations to laboratory mice 1 h before γ-irradiation in a lethal dose of 8 Gy. The correlation of protonophore activity on bilayer lipid membranes with radioprotective (in mice) and uncoupling activity (in mitochondria) indicates a molecular protonophore uncoupling radioprotective mechanism of DBA action on mitochondria, which manifests in temporary partial inhibition of energy production. The effectiveness of DBA depends on the position and the degree of dissociation of OH-groups and increased in the presence of a sulfur-containing bridge and substituents in the series Br->Cl->NO2->COOCH3->COOH-. The higher radioprotective effect was observed for more effective uncouplers of the processes of oxidative phosphorylation and respiration of mitochondria, DBA1 preparations with OH-groups in the 2nd position of the benzene rings (80-100%), than for DBA2 with OH- in the 4th position (40-60%). The radioprotective effect of DBA was related to their antioxidant activity during and after irradiation to a lesser extent than with their uncoupling efficiency. At the cellular level, the radioprotective mechanism of DBA is related to temporary hypoxia and inhibition of metabolism leading to inhibition of generation of ROS, radicals, and LPO products.Macrophages play the key role in the regulation of neuroregeneration. For evaluation of the neuroregenerative potential of M2 macrophages, we studied the effect of macrophages polarized with IL-4 (M2a (IL-4)) and by efferocytosis under conditions of serum deprivation (LS, Low Serum; M2(LS)) on proliferative activity and apoptosis of SH-SY5Y cells under conditions of deficiency of growth/serum factors. Conditioned media of both M2(LS) and M2a(IL-4) stimulated proliferation of SH-SY5Y cells. Moreover, soluble factors of M2(LS) and M2a(IL-4) reduced the degree of early apoptosis of SH-SY5Y cells and the protective effect of M2(LS) was observed at earlier terms of culturing. Our findings suggest that M2 macrophages have high neuroregenerative potential that is mediated through soluble factors and manifests itself both in stimulation of proliferation and inhibition of apoptosis of SH-SY5Y cells.
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