Krasnoyarsk State Medical University

Chronic back pain (CBP) associated with intervertebral disc degeneration (IVDD) is a leading cause of medical consultations, decreased quality of life, and temporary and permanent disability. The mechanisms of CBP development and persistence in patients with IVDD have been studied for many years, but this issue remains far from resolved. The search for predictive biomarkers that could help identify patients with IVDD at high risk for CBP continues. In recent decades, research has shown increasing interest in identifying epigenetic biomarkers for this disorder. to summarize the results of preclinical and clinical studies on the role of microRNAs (miRs) as epigenetic biomarkers of the development and progression of CBP in patients with IVDD. English-language articles; original experimental (preclinical) studies; original clinical study; assessment of changes in systemic (in the blood) and/or local (in the intervertebral disk (IVD)) levels of miR expression in IVDD, either independently or in comparison with healthy controls; and studies that were completed and the results of which were published. PubMed, Springer, Google Scholar, Scopus, Oxford Press, Cochrane, and e-Library databases. Charting for this scoping review involved developing a data extraction form to summarize extracts and organize data from included studies. This was an iterative process where the charting tables and figures may be refined as the review progresses. 126 studies were analyzed in detail, focusing on their study designs and comparing changes in miR expression in animal models of IVDD and in patients with IVDD compared to healthy controls. During the preparation of this scoping review and upon subsequent detailed review of the original publications, it turned out that the results of one study were not justified by the authors due to identified technological problems (the article was withdrawn by the editorial board of the journal). Therefore, we excluded the results of this study from the subsequent analysis. As a result, this section summarizes the results of 60 preclinical and 65 clinical studies. Some miRs (e.g., miR-21 and miR-132) are associated with the regulation of inflammatory pathways that contribute to increased degradation of IVD extracellular matrix and enhanced nociceptive signaling through various mechanisms, contributing to the progression of CBP. Other miRs (e.g., miR-145 and miR-223) exert protective effects, enhance regenerative potential, and alleviate CBP. Despite the promising results of these studies, there are limitations in the use of miRs as perspective epigenetic biomarkers of CBP in patients with IVDD because the pattern of potentially predictive and protective miRs in relation to the mechanisms of CBP formation and progression in IVDD has not yet been sufficiently studied. The results of some preclinical and clinical studies are contradictory. Further research is needed to clarify the role of miR signatures in animal models and clinical trials on IVDD-specific CBP.

IIn this study, unstabilized zirconium dioxide (ZrO2-x) nanopowders are synthesized using vacuum arc deposition, and the effect of reaction chamber pressure on their phase composition, morphology, and dielectric properties is comprehensively investigated. X-Ray diffraction and Fourier transform IR spectroscopy reveal that a decrease in pressure increases the tetragonal ZrO2 phase content from 52% to 90% and the concentration of oxygen vacancies. Impedance analysis shows that sample N30 possesses the lowest resistance (~11.5 kOhm) and the best ionic conductivity, due to the high mobility of vacancies. At the same time, sample N90 exhibits pronounced dielectric properties and interfacial polarization. It is shown that varying the synthesis conditions allows for targeted control of the electrical conductivity and polarization properties of ZrO2-x, which opens up prospects for its use as a functional material for solid oxide electrolytes, sensors, and dielectric capacitors.

Introduction. The combination of esophageal pathology and bronchial asthma is frequently encountered in clinical practice, but in some cases it may remain unrecognized due to diagnostic difficulties and a lack of clinical suspicion. Aim. To evaluate the structural, functional, and laboratory abnormalities detected in patients with bronchial asthma combined with esophageal pathology. Materials and methods. The study was conducted at the Allergology Department of the Krasnoyarsk Regional Clinical Hospital. Sixty-nine patients admitted for inpatient treatment with a diagnosis of bronchial asthma were examined. Based on clinical and anamnestic data, the patients were divided into two groups: those with bronchial asthma without esophageal pathology (Group 1: 38 patients (55.07%)) and those with bronchial asthma combined with esophageal pathology (Group 2: 31 patients (44.93%)). The examination methods included: anamnestic analysis, physical examination, completion of the ACQ-5, ACT, GERDQ, and dysphagia questionnaires, instrumental tests (spirography with a bronchodilator, fibrogastroduodenoscopy), laboratory tests, and esophageal morphological examination. Results. Patients with asthma combined with esophageal pathology had a significantly higher number of daytime and night-time attacks and, consequently, a higher need for SABA. According to spirometry data, fixed airway obstruction was significantly more common among patients in Group 2. Immune status showed a significant decrease in NKT cells in Group 2 patients. A decrease in NKT cells in patients with bronchial asthma combined with esophageal pathology, as well as a negative association with fungal esophagitis, may indirectly indicate a decrease in epithelial barrier function and, consequently, a greater vulnerability to environmental factors, as also confirmed by the AQLQ questionnaire scores in the “environment” domain. Conclusions. The obtained data confirm the aggravating effect of esophageal pathology on the course of bronchial asthma and also indirectly indicate changes in the mucosal immune system, which may lead to combined damage to the mucous membranes of the esophagus and respiratory tract.

Tocilizumab (TCZ) is widely used in rheumatoid arthritis (RA) and may be administered using different dosing regimens, including the standard dose (SD) of 8 mg/kg and regimens involving dose reduction or escalation depending on the clinical response. Under current healthcare conditions, assessment of the clinical and economic feasibility of drug-dosing strategies is particularly relevant. Objective : to evaluate, from the perspective of the Russian healthcare system, the clinical and economic feasibility of a TCZ dose de-escalation strategy (DDS) from 8 to 4 mg/kg after remission is achieved and a dose escalation strategy (DES) from 4 to 8 mg/kg if remission is not achieved, compared with the SD of 8 mg/kg in patients with RA. Material and methods . A decision-tree model with 1and 3-year time horizons was developed to compare the three TCZ dosing strategies. Costminimization analysis, budget impact analysis, and one-way sensitivity analysis were performed. Results and discussion . Over a 1-year time horizon, DES provided savings of 169,850 rubles (28.1%) per patient compared with SD, whereas DDS provided savings of 58,188 rubles (9.6%). Over a 3-year time horizon, savings amounted to 168,849 rubles (10.3%) and 95,848 rubles (5.8%) for DES and DDS, respectively. According to the budget impact analysis, transferring a proportion of patients to DES could reduce costs by 1.0–1.7 billion rubles over 3 years, whereas transition to DDS could reduce costs by 0.6–1.0 billion rubles. Conclusion . Within the adopted assumptions, the model demonstrates a potential reduction in direct drug costs when using strategies involving controlled dose reduction or initiation at a lower dose followed by escalation. Owing to the limited availability of direct comparative data and regulatory restrictions in the Russian Federation, the results should be regarded as a scenario-based pharmacoeconomic assessment requiring validation using Russian data.

The definition of cardiogenic cognitive disorders (CCD) was first proposed in the mid20th century, but in subsequent years it was unjustifiably omitted from current clinical guidelines. Preclinical and clinical studies using modern methods of laboratory, functional, and radiological diagnostics confirm the significance and specific features of CCD development compared with those in cerebrovascular pathology. The pathophysiological mechanisms of CCD associated with acute myocardial infarction (AMI) include vascular dysregulation, atherosclerosis, platelet activation, microinfarctions, perivascular inflammation, impaired hemostasis, and a dysfunctional neurohumoral response. These mechanisms may lead to the occurrence of clinically silent microinfarctions, as well as impaired functionality of the white matter in the cerebral cortex. Such pathologies can cause cerebral hypoperfusion and microvascular ischemia, which in turn contributes to the enlargement of periventricular spaces and the development of cerebral amyloid angiopathy, and also leads to hippocampal sclerosis. Objective : To study the role of circulating microRNAs as epigenetic biomarkers of cognitive disorder associated with acute myocardial infarction in an animal model. Materials and Methods: At the first part of this experimental study, the dynamics of cognitive deficit and neurological status were studied in sexually mature Wistar rats. The total sample of experimental animals was divided into three groups, including the study group — AMI without therapy (n1 = 10), the comparison group — AMI with CCD therapy (n2 = 15), and the control group — without AMI and without therapy (n3 = 10). The observation groups were divided in equal numbers for the study of miR-19b-3p and miR-134-5p. The experimental model of AMI according to the method of N. Elmali was used. Blood sampling from the tail vein and assessment of cognitive functioning (the Morris test) and neurological deficit (neuropsychological test — NSS) were performed before the experiment and 10 days later. Three strategies were used for the treatment of early CCD: monotherapy with rosuvastatin, monotherapy with Prospekta®Vet, and combination therapy with rosuvastatin and Prospekta®Vet. To exclude the error of multiple comparisons before pairwise comparison using the Mann–Whitney test, all groups compared with each other were preliminarily compared using the Kruskal–Wallis test. Results : Baseline indicators of locomotor activity and cognitive functions according to the Morris test, as well as neurological status according to the NSS scale, were comparable in all groups (pvalue > 0.05). On day 10 after AMI modeling, no statistically significant changes in the parameters of the Morris test (speed, time in the target sector, distance, platform search time) were detected in any of the groups (p-value > 0.05). At the same time, significant intergroup differences were found according to the NSS test (p-value = 0.018, the Kruskal–Wallis test), due to an increase in neurological deficit in the subgroup receiving Prospekta®Vet monotherapy compared with the control group (pvalue = 0.003) and the AMI group without therapy (p-value = 0.005). Analysis of the dynamics of neurological symptoms (difference in NSS test scores) confirmed a trend toward its increase in the Prospekta®Vet monotherapy group, which was significantly higher than in the combination therapy group (p-value < 0.05). In 40% of animals in the AMI group without therapy and the Prospekta®Vet monotherapy group, moderate neurological deficit developed, whereas in the subgroups receiving rosuvastatin and combination therapy with rosuvastatin and Prospekta®Vet, this indicator was significantly lower. Conclusions : The present study successfully tested the AMI model according to the method of N. Elmali for studying CCD associated with AMI, revealing reproducible neurological deficit in the absence of gross cognitive deficit in experimental animals in the acute period. The most promising therapeutic strategy for the correction of early CCD associated with AMI is the combined administration of rosuvastatin and Prospekta®Vet at moderate therapeutic doses. To translate the obtained results into real clinical practice, a further "bridging" clinical study involving middle-aged adults with AMI is required.