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Rheological studies of soils were carried out by S.S. Vyalov, M.N. Gol’dshtejn, N.N. Maslov, G.I. Ter-Stepanyan, S.R. Meschyan, A.L. Gol’din, Z.G. Ter-Martirosyan and many others. On the basis of existing rheological soil models, a new universal rheological equation was proposed in Ter-Martirosyan’s dissertation, which allows describing kinematic shear, creep and stress relaxation at the same parameters. Experimental studies of the soil were carried out in a simple shear device in a kinematic loading mode at a shear displacement rate u̇= 0.05 mm/min and at two values of compaction loads (σ1 < σ2). Based on the results of the experimental studies, the parameters of the elastoviscoplastic model were determined and graphs of the dependence of shear stresses on time were plotted, which clearly show the high convergence of the experimental and theoretical curves.

Dravet syndrome is a severe genetic epilepsy primarily caused by de novo mutations in a voltage-activated sodium channel gene (SCN1A). Patients face life-threatening seizures that are largely resistant to available anti-seizure medications. Preclinical Dravet syndrome animal models are a valuable tool to identify candidate anti-seizure medications for these patients. Among these, scn1lab mutant zebrafish, exhibiting spontaneous seizure-like activity, are particularly amenable to large-scale drug screening. Thus far, we have screened more than 3000 drug candidates in scn1lab zebrafish mutants, identifying valproate, stiripentol, and fenfluramine e.g. Food and Drug Administration-approved drugs, with clinical application in the Dravet syndrome population. Successful phenotypic screening in scn1lab mutant zebrafish is rigorous and consists of two stages: (i) a locomotion-based assay measuring high-velocity convulsive swim behaviour and (ii) an electrophysiology-based assay, using in vivo local field potential recordings, to quantify electrographic seizure-like events. Historically, nearly 90% of drug candidates fail during translation from preclinical models to the clinic. With such a high failure rate, it becomes necessary to address issues of replication and false positive identification. Leveraging our scn1lab zebrafish assays is one approach to address these problems. Here, we curated a list of nine anti-seizure drug candidates recently identified by other groups using preclinical Dravet syndrome models: 1-Ethyl-2-benzimidazolinone, AA43279, chlorzoxazone, donepezil, lisuride, mifepristone, pargyline, soticlestat and vorinostat. First-stage locomotion-based assays in scn1lab mutant zebrafish identified only 1-Ethyl-2-benzimidazolinone, chlorzoxazone and lisuride. However, second-stage local field potential recording assays did not show significant suppression of spontaneous electrographic seizure activity for any of the nine anti-seizure drug candidates. Surprisingly, soticlestat induced frank electrographic seizure-like discharges in wild-type control zebrafish. Taken together, our results failed to replicate clear anti-seizure efficacy for these drug candidates highlighting a necessity for strict scientific standards in preclinical identification of anti-seizure medications.

Ultraviolet cross-linking (UVCL) of corneal collagen is one of the leading methods for treating primary progressive keratectasia. Purpose: to evaluate the effectiveness and safety of a new Russian-produced device for UVCL, KERATOLINK, in treating patients with stage I–II keratoconus and pellucid marginal corneal degeneration (PMCD). Material and methods. UVCL was performed in 36 patients (46 eyes) aged 18 to 35 years, including 22 patients (30 eyes) with stage I–II keratoconus and 14 patients (16 eyes) with PMCD. Three programs were used: 1 — standard UVCL with radiation intensity from 2.5 to 3.0 mW/cm2 and 30-minute exposure time (8 patients, 10 eyes); 2 — accelerated UVCL 1: from 8.0 to 9.0 mW/cm2 and exposure time 10 min (20 patients, 25 eyes); 3 — accelerated UVCL 2 with radiation intensity from 16.0 to 18.0 mW/cm2 and 5-minute exposure time (8 patients, 11 eyes). The patients were examined before UVCL, then a week, 1, 3, 6 months after it. The examination included vision acuity, autorefkeratometry, biomicroscopy, Scheimpflug analysis on a Galilei G6 device (Ziemer, Switzerland), optical coherence tomography of the cornea (Anterion, Heidelberg Engineering, Germany), aberrometry (OPD-scan III, Nidek, Japan), confocal biomicroscopy (ConfoScan 4, Nidek, Japan), and determination of biomechanical parameters of the cornea - corneal resistance factor (CRF) and corneal hysteresis (CH) on an ORA device (Reichert Inc., USA). Results. 6 months after UVCL, an increase in visual acuity from 0.56 ± 0.16 to 0.68 ± 0.13 was noted in stage I-II keratoconus, and from 0.66 ± 0.17 to 0.75 ± 0.14 (p < 0.05) in PMCD. Flattening of the cornea at the steepest point increased from 54.46 ± 4.39 to 52.87 ± 4.26 D and from 52.64 ± 2.88 to 51.53 ± 2.84 D, while the rigidity increased in CRF from 6.93 ± 1.00 to 8.38 ± 1.00 mm Hg and from 8.02 ± 0.68 to 9.13 ± 0.97 mm Hg. (p < 0.03), and CH increased from 7.64 ± 0.47 to 8.61 ± 0.73 mm Hg and from 6.89 ± 1.20 to 8.17 ± 0.90 mm Hg (p < 0.05). The analysis of various UVCL programs revealed no difference in the recovery period and showed comparable clinical and functional results. Conclusion. The new KERATOLINK device is shown to be effective and safe in the treatment of stage I–II keratoconus and PMCD. A decrease in ophthalmometry indicators, and an increase in corneal rigidity and visual acuity indicate an improvement in the optical and biomechanical properties of the patients’ cornea and stabilization of the pathological process. The use of local UVCL and accelerated algorithms with a significant reduced exposure time improves the comfort and tolerability of the procedure, and also reduces the risk of complications. The KERATOLINK device provides a personalized approach to the treatment of patients due manual and stationary use options, the availability of standard and accelerated UVCL programs, providing for the choice of power and duration of the procedure, with smooth adjustment and fixation of the size and the area of treatment. The laser focal length control system ensures the maintenance of the required UVCL intensity regardless of the size of the impact spot. It has good prospects for clinical practice.

Introduction. Graft revascularization in deficient arterial blood flow is usually performed by X-ray endovascular stenting procedure and/or by reconstruction of vascular anastomosis. The most serious complication of catheter intervention is a hepatic artery rupture and the critical ischemia of the liver graft.Objective. To discuss the successful treatment of a hepatic artery rupture which occurred during X-ray endovascular revascularization of the liver graft.Case report. A 48-year-old female patient with advanced alveococcosis underwent orthotopic cadaveric liver transplantation. After restoring the blood flow, it was found to be of low-velocity with RI 0.4 in the common hepatic artery. The gastrointestinal duodenal and splenic arteries were ligated. On the second day, a relaparotomy was performed because of intraabdominal bleeding originated from the parenchyma of the 7th–8th segments. Bleeding was arrested. After 18 hours, a selective angiography revealed stenosis up to 90% in the native hepatic artery. After balloon predilatation, stenting was performed, which accidentally caused the artery rupture. The further treatment included relaparotomy and reanastomosing. The patient was discharged from hospital on Day 19 after transplantation.Conclusion. Low velocity blood flow in the hepatic artery did not meet an adequate level even after the ligation of the gastrointestinal duodenal and splenic arteries. We performed the reconstruction of anastomosis. Another possible approach could be a catheter revascularization. The decision should be made considering the specific disorders of regional blood flow, their origin, and the vascular anatomy. The rupture of the artery in the reported case was caused by disproportionate diameters of the stent and vessel.

This study investigates the shift in private banking from conventional creditworthiness assessment to advanced machine learning (ML) models. Employing a synthesis technique, this study conducts a review of literature and case studies and highlights how ML models, through the integration of alternative big data and advanced algorithms, can enhance accuracy in forecasting customer defaults and contribute to financial inclusion. The research underscores legal and ethical concerns regarding alternative data processing, necessitating thorough compliance checks by banks and regulatory authorities. Furthermore, it underlines the necessity for banks and regulators to develop technical skills to ensure ML models remain transparent and understandable, avoiding the pitfalls of becoming “black boxes”. Future research is suggested to explore risk mitigation strategies based on its ML deployment approach, technical aspects of ML algorithms, and the impact of ML-based credit scoring on broader macro-financial linkages.

Delayed-type drug hypersensitivity reactions are major causes of morbidity and mortality. The origin, phenotype, and function of pathogenic T cells across the spectrum of severity require investigation. We leveraged recent technical advancements to study skin-resident memory T cells (TRMs) versus recruited T cell subsets in the pathogenesis of severe systemic forms of disease, Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) and drug reaction with eosinophilia and systemic symptoms (DRESS), and skin-limited disease, morbilliform drug eruption (MDE). Microscopy, bulk transcriptional profiling, and single-cell RNA-sequencing (scRNA-Seq) plus cellular indexing of transcriptomes and epitopes by sequencing (CITE-Seq) plus T cell receptor sequencing (TCR-Seq) supported clonal expansion and recruitment of cytotoxic [CD8.sup.+] T cells from circulation into skin along with expanded and nonexpanded cytotoxic [CD8.sup.+] skin TRM in SJS/TEN. Comparatively, MDE displayed a cytotoxic T cell profile in skin without appreciable expansion and recruitment of cytotoxic [CD8.sup.+] T cells from circulation, implicating TRMs as potential protagonists in skin-limited disease. Mechanistic interrogation in patients unable to recruit T cells from circulation into skin and in a parallel mouse model supported that skin TRMs were sufficient to mediate MDE. Concomitantly, SJS/TEN displayed a reduced Treg signature compared with MDE. DRESS demonstrated recruitment of cytotoxic [CD8.sup.+] T cells into skin as in SJS/TEN, yet a pro-Treg signature as in MDE. These findings have important implications for fundamental skin immunology and clinical care., Introduction Delayed-type drug hypersensitivity reactions (dtDHRs) are a major cause of morbidity and mortality, with considerable cost to healthcare systems (1-5). Skin is the most commonly affected organ. Severity ranges [...]

Emotional burnout among physicians is a serious problem that can affect their health and the quality of medical care. This condition occurs when physicians experience excessive stress and pressure at work, often due to high demands and expectations imposed on them by patients. This study aims to assess the experience and factors associated with emotional burnout among health workers who deal with COVID-19-positive patients. The study population includes employees at the infectious diseases hospital and the inpatient clinical hospital examined using the Maslach Burnout Inventory. The prevalence of high emotional exhaustion among infectious diseases specialists and inpatient physicians was 51.2 ± 3.4 % and 43.3 ± 8.1 %, respectively. The prevalence of high depersonalization was 39.4 ± 7.9 % and 40.5 ± 8.1 %, respectively. Finally, the prevalence of reduced professional efficacy was 26.3 ± 7.1 % and 41.3 ± 8.3 %, respectively. The main burnout contributors were a heavy workload, a high risk of infection, the lack of protective equipment, insufficient social support, constant interaction with suffering patients, and work-life imbalance. To prevent burnout among health workers who deal with COVID-19-positive patients, it is best to create a working environment that is conducive to good physical and mental health, implement stress management courses, and provide employees with enough time for rest and recovery. These preventive measures will help to improve the quality of health care. The findings of the study can be utilized for the development of support programs for healthcare professionals, improvement of working conditions, and reduction of the risk of emotional burnout.

BackgroundPneumonia is the primary cause of death among HIV-infected children in Africa, with mortality rates as high as 35-40% in infants hospitalized with severe pneumonia. Bacterial pathogens and Pneumocystis jirovecii are well known causes of pneumonia-related death, but other important causes such as cytomegalovirus (CMV) and tuberculosis (TB) remain under-recognized and undertreated. The immune response elicited by CMV may be associated with the risk of developing TB and TB disease progression, and CMV may accelerate disease caused both by HIV and TB. Minimally invasive autopsies confirm that CMV and TB are unrecognized causes of death in children with HIV. CMV and TB may also co-infect the same child. The aim of this study is to compare the impact on 15-day and 1-year mortality of empirical treatment against TB and CMV plus standard of care (SoC) versus SoC in HIV-infected infants with severe pneumonia.MethodsThis is a Phase II-III, open-label randomized factorial (2 × 2) clinical trial, conducted in six African countries. The trial has four arms. Infants from 28 to 365 days of age HIV-infected and hospitalized with severe pneumonia will be randomized (1:1:1:1) to (i) SoC, (ii) valganciclovir, (iii) TB-T, and (iv) TB-T plus valganciclovir. The primary endpoint of the study is all-cause mortality, focusing on the short-term (up to 15 days) and long-term (up to 1 year) mortality. Secondary endpoints include repeat hospitalization, duration of oxygen therapy during initial admission, severe and notable adverse events, adverse reactions, CMV and TB prevalence at enrolment, TB incidence, CMV viral load reduction, and evaluation of diagnostic tests such as GeneXpert Ultra on fecal and nasopharyngeal aspirate samples and urine TB-LAM.DiscussionGiven the challenges in diagnosing CMV and TB in children and results from previous autopsy studies that show high rates of poly-infection in HIV-infected infants with respiratory disease, this study aims to evaluate a new approach including empirical treatment of CMV and TB for this patient population. The potential downsides of empirical treatment of these conditions include toxicity and medication interactions, which will be evaluated with pharmacokinetics sub-studies.Trial registrationClinicalTrials.gov , NCT03915366, Universal Trial Number U111-1231-4736, Pan African Clinical Trial Registry PACTR201994797961340.

Relevance. Magnets have long been used to treat various diseases, especially in inflammatory processes. According to existing historical data, magnetotherapy was already used in ancient times by the Chinese, Egyptians and Greeks. Different magnetic field strengths affect cells in different ways, with medium-strength magnetic fields being the most widely used. The review presents a brief history and current state of the issue of using a magnetic field in bone tissue regeneration. Modern knowledge about the mechanisms of physiological and reparative regeneration, restoration of bone tissue is clarified, and modern areas of bone tissue engineering are considered, taking into account the characteristics of microcirculation and the effect of a magnetic field on the physiology of bone tissue and reparative regeneration. One of the key findings of the review is that the magnetic field improves bone tissue repair by influencing the metabolic behavior of cells. Studies show that magnetotherapy promotes the activation of cellular processes, accelerates the formation of new bone tissue and improves its quality. It is also noted that the magnetic field has a positive effect on microcirculation, improving the blood supply to tissues and facilitating a better supply of nutrients to the site of injury. This contributes to faster wound healing and early rehabilitation of patients. Conclusion. Magnetotherapy is one of the effective physical and rehabilitation methods of treatment that will become increasingly important in modern medicine. However, further research is needed to better understand the mechanisms of action of a magnetic field on bone tissue and to determine the optimal parameters for its application.

Scleral rigid contact lenses efficiently correct the vision of patients with irregular corneas. Purpose. To study the features of contact correction and visual rehabilitation of patients with irregular corneal surface using individual scleral rigid contact lenses. Results. Three clinical cases of successfully selected rigid individual scleral lenses for patients with an irregular corneal surface that appeared after a penetrating keratoplasty, implantation of intrastromal corneal segments, and eye injury. The expected refractive result was achieved; high tolerance and good adaptation to lenses was revealed. Conclusion. Scleral RCL can be successfully used in patients with irregular cornea to improve visual acuity, reduce the number of aberrations, restore binocular vision and social adaptation.