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Abstract Analysis of serial liquid biopsy (LB) samples has been found to be a promising approach for the monitoring of tumor dynamics in the course of therapy for patients with colorectal cancer (CRC). Currently, somatic mutations are used for tracing the dynamics of the tumor via LB. However, the analysis of the dynamic changes in the molecular signatures such as microsatellite instability (MSI) is not currently used. We hypothesized that changes in blood MSI burden (bMSI) could be registered using serial LB sampling in the course of immune checkpoint inhibitors (ICI), and that its changes could potentially correlate with treatment outcomes. We report the preliminary findings of the observational trial launched to study (NCT06414304) the dynamics of bMSI in 9 MSI-positive CRC patients receiving ICI. NGS-based MSI testing was performed on both pre-treatment FFPE and serial LB samples. For patients who had detectable bMSI burden in any of the LB samples (n = 8, 89%), median bMSI was 1.4% (range, 0.01-40%). Among patients with detectable MSI in available FFPE samples, median MSI burden was 29.3% (range, 10–40%). bMSI detected in baseline LB and FFPE samples were positively correlated (Pearson’s R 0.47). Maximal variant allele frequencies of driver mutations observed in LB were also positively correlated with bMSI burden (Pearson’s R 0.7). Patients who had clinical benefit had undetectable bMSI burden at follow-up. Our results provide the rationale for further validation of bMSI as a predictive biomarker of ICI in MSI-positive patients.

Aim – to develop an applied prognostic calculator for the rate of progression of CKD in elderly patients with type 2 diabetes, which makes it possible to identify a group of high rate of GFR reduction in conditions of routine outpatient admission. Material and methods. 69 clinical indicators were studied, the interrelationships and significance of differences in parameters in the groups identified according to the original diagnostic parameter, the glomerular filtration rate reduction index with a threshold value of 3.83 ml/min/1.73 m2 per year, above which the rate of progression of CKD was considered high. Results. By using regression analysis, significant factors for the prognostic calculator were identified: the duration of diabetes and insulin therapy, concomitant diagnosis of obesity, pulse in the ankle artery, severe stage of polyneuropathy, risk group IV of hypertension, treatment with sulfonylureas, the number of antihypertensive drugs taken. When evaluating the information capacity and predictive ability of the calculator, the area under the AUC ROC curve was 0.89 (0.80; 0.99) p 0.001, which characterizes the quality of the diagnostic technique as high. Conclusion. The presented calculator gives the doctor the opportunity to identify a group of patients with the risk of rapid progression of CKD directly on an outpatient basis.

Accurate tracking of the same neurons across multiple days is crucial for studying changes in neuronal activity during learning and adaptation. Advances in high-density extracellular electrophysiology recording probes, such as Neuropixels, provide a promising avenue to accomplish this goal. Identifying the same neurons in multiple recordings is, however, complicated by non-rigid movement of the tissue relative to the recording sites (drift) and loss of signal from some neurons. Here, we propose a neuron tracking method that can identify the same cells independent of firing statistics, that are used by most existing methods. Our method is based on between-day non-rigid alignment of spike-sorted clusters. We verified the same cell identity in mice using measured visual receptive fields. This method succeeds on datasets separated from 1 to 47 days, with an 84% average recovery rate.

SCIENTIFIC RELEVANCE. Potency testing of recombinant interferons requires a reference standard. The availability of International Standards (ISs) that are commonly used to assess the quality of recombinant interferons is currently limited. Therefore, the quality of interferons should be assessed using pharmacopoeial reference standards (RSs) certified using ISs (if available).AIM. This study aimed to certify a pharmacopoeial RS for potency testing of recombinant interferon α-2b.MATERIALS AND METHODS. The potency determination involved comparing the inhibition of the virus-induced cytopathic effect observed in cell culture with the candidate RS and the WHO International Standard for Human rDNA-derived interferon α-2b. The study used A-549 and MDBK cell lines with encephalomyocarditis (EMC) and vesicular stomatitis (VSV) viruses. The authors followed the requirements of the State Pharmacopoeia of the Russian Federation (Cell-Culture Bioassays for Interferon Products, OFS.1.7.2.0002.15). The results were recorded using instrumental and visual methods. The calculations used mathematical statistics. To factor in the influence of intermediate precision, the authors applied Student’s t-test.RESULTS. The authors developed a certification programme and procedure and certified the pharmacopoeial RS for recombinant human interferon α-2b (rhIFN α-2b) to identify the corresponding medicinal products (by virus neutralisation) and test their potency (by antiviral activity in cell culture). Upon receipt, the candidate RS was verified for compliance with regulatory specifications. According to the test results, the potency of the candidate pharmacopoeial RS was 4.47×10⁸ IU/mL, and the expanded uncertainty was 8.12×10⁷ IU/mL, with a coverage factor of k=2 and a confidence level of 95%. The pharmacopoeial RS for rhIFN α-2b was considered to have the same shelf-life period as the corresponding medicinal products if stored at a temperature not higher than –40 ºC. When thawed, the pharmacopoeial RS for rhIFN α-2b can be stored at a temperature of 2–8 ºC for up to 1 month.CONCLUSIONS. Upon certification for potency testing, the pharmacopoeial RS for rhIFN α-2b has been included in the Register of Reference Standards of the Russian Pharmacopoeia as Recombinant Human Interferon α-2b (Potency) FSO.3.2.00455. The introduction of this pharmacopoeial RS will help to conduct the identification and potency testing of all Russian interferon α-2b products at an appropriate scientific and methodological level. As a result, Russian pharmaceutical manufacturers and quality control agencies will no longer depend on imported ISs.

Aim. To assess the features of the clinical picture of coronary artery disease (CAD) and the prognosis of patients with myocardial infarction with depressive disorder (DD). Materials and methods. We examined 101 patients with stable CAD who had myocardial infarction more than six months ago: 67 CAD patients with depression (Group 1) and 34 CAD patients without depression (Group 2). The clinical picture of CAD was assessed by complaints, angina self-monitoring diaries, and exercise tests. The presence and severity of DD was determined using psychometric scales: BDI (Beck Depression Scale), HADS (Hospital Anxiety and Depression Scale) and the opinion of a psychiatrist. Five-year survival information was obtained through telephone interviews with patients and their relatives. Results. In patients with CAD and DD in comparison with patients without DD self-monitoring diaries revealed more frequent angina attacks: 9 [6; 12] vs 6 [4; 7] per week (p=0.0001), the greater need for sublingual nitrates: 2 [0; 9] pills vs 0 [0; 4] pills (p=0.0001). DD significantly reduced exercise tolerance: 370 [250; 450] meters vs 435 [350; 500] meters using the six-minute walk test (p=0.04), according to the results of bicycle ergometry – 50 [25; 75] W vs 75 [50; 75] W (p=0.03). After 5 years of follow-up patients with comorbidities (CAD and DD) had a greater number of deaths: 13 (19.4%) vs 2 (5.9%), respectively, survived – 54 (80.6%) vs 32 (94.1%) (Gehan–Wilcoxon test, p=0.04). Conclusion. The comorbidity CAD and DD leads to a worsening of the clinical course of CAD and prognosis, which actualizes the need for verification of the diagnosis of DD and timely prescription of antidepressant therapy.

In this study, we have estimated alcohol consumption and alcohol-associated incidence in the RF regions in the ‘before crisis’ (2017–2019) and ‘crisis’ (2020–2022) periods. We identified types of the RF regions using hierarchical cluster analysis (Ward’s method) and relying on indirect indicators of alcohol consumption. As a result, we established considerable differences between the macro-regions (the Federal Districts) and RF regions as per alcohol consumption and severity of its outcomes. Poles in this differentiation are represented by ‘favorable’ regions in the Southern Russia where alcohol sales, alcohol-associated crime and incidence are low and ‘unfavorable’ regions located in the Far East and southern Siberia where alcohol-associated crime and incidence are high. We have shown in this study that retail alcohol sales cannot be considered a sufficient indicator to describe alcohol use in a given region. Thus, considerable volumes of alcohol sales involve severe socially significant outcomes in some regions (for example, the Khabarovsk region and Primorye) whereas such outcomes do not occur in other regions with similarly high alcohol sales (Moscow, Saint Petersburg, the Moscow region and the Leningrad region). The level of socioeconomic welfare on a given territory is confirmed as a significant determinant of alcohol consumption. We have also analyzed a correlation between economic vulnerability of RF regions during the ‘pandemic’ and ‘sanction’ crises and levels of alcohol consumption. The analysis revealed that large industrial regions, though expected to be vulnerable, turned out to be quite stable (it is probable due to delayed macroeconomic effects). We have not been able to identify any resources of improving a tense situation with alcohol consumption in economically unfavorable but less vulnerable subsidized agricultural regions. In general, the crisis period of 2020–2022 can be considered a source of additional health risks for the population in the RF regions where the situation with alcohol consumption was rather unfavorable in the ‘before crisis’ period.

Abstract Brachyury, a member of T-box gene family, is widely known for its major role in mesoderm specification in bilaterians. It is also present in non-bilaterian metazoans, such as cnidarians, where it acts as a component of an axial patterning system. In this study, we present a phylogenetic analysis of Brachyury genes within phylum Cnidaria, investigate differential expression and address a functional framework of Brachyury paralogs in hydrozoan Dynamena pumila. Our analysis indicates two duplication events of Brachyury within the cnidarian lineage. The first duplication likely appeared in the medusozoan ancestor, resulting in two copies in medusozoans, while the second duplication arose in the hydrozoan ancestor, resulting in three copies in hydrozoans. Brachyury1 and 2 display a conservative expression pattern marking the oral pole of the body axis in D. pumila. On the contrary, Brachyury3 expression was detected in scattered presumably nerve cells of the D. pumila larva. Pharmacological modulations indicated that Brachyury3 is not under regulation of cWnt signaling in contrast to the other two Brachyury genes. Divergence in expression patterns and regulation suggest neofunctionalization of Brachyury3 in hydrozoans.

Planktonic lifestyle of polyps in representatives of Margelopsidae are very different from all other species in the hydrozoan clade Aplanulata. Their evolutionary origin and phylogenetic position have been the subject of significant speculation. A recent molecular study based only on COI data placed Margelopsidae as a sister group to all Aplanulata, an unexpected result because margelopsid morphology suggests affiliation with Tubulariidae or Corymorphidae. Here we used multigene analyses, including nuclear (18S rRNA and 28S rRNA) and mitochondrial (16S rRNA and COI) markers of the hydroid stage of the margelopsid species Margelopsis haeckelii and the medusa stage of Margelopsis hartlaubii to resolve their phylogenetic position with respect to other hydrozoans. Our data provide strong evidence that M. haeckelii, the type species of Margelopsis, is a member of the family Corymorphidae. In contrast, M. hartlaubii is sister to Plotocnide borealis, a member of Boreohydridae. These results call into question the validity of the genus Margelopsis and the family Margelopsidae. The systematic position of M. haeckelii is discussed in light of the phylogeny of Corymorphidae.

Introduction: Postoperative drain loss can exceed intraoperative blood loss and affect the severity of the patient’s condition. Aim: The objective of the study was to find significant predictors of postoperative blood loss in surgery for idiopathic scoliosis.Materials and methods: We analyzed the data of 140 patients with idiopathic scoliosis. One hundred three patients (group 1) un-derwent Smith-Petersen osteotomy as part of the multilevel pedicle screw fixation; 37 patients (group 2) required no spinal osteotomy. Correlation and regression analysis of the data was performed.Results: There were significant differences between the groups in the number of fixed segments (p

Background. The article reflects the clinical significance of the early diagnosis of toxic hepatitis in patients who have undergone a new coronavirus infection with the determination of clinical and laboratory predictors of the response to therapy. A dynamic analysis of the effectiveness of toxic hepatitis therapy in patients of three experimental groups and a control group is presented. Aim. The aim of the present study is to increase the effectiveness of the treatment of toxic hepatitis in patients who have undergone COVID-19. Materials and methods. On the basis of the newly created infection centers of the Central Clinical Hospital RZhD-Medicine and Vishnevsky 3-rd Central Military Clinical Hospital 996 patients with COVID-19, who had clinical and laboratory signs of toxic liver damage (cytolytic and/or cholestatic syndromes) against the background of COVID-19 therapy. Results. On the 14th day from the start of therapy in group 3, there was a significant decrease in the clinical manifestations of jaundice in 163 (72.8%) patients, on the 21st day of treatment, this symptom was stopped in all patients. In groups 1 and 2, the decrease in clinical manifestations of jaundice was significantly lower 122 (55.2%) and 134 (58.8%); p0.05. At the end of therapy, no manifestations of jaundice were observed in all experimental groups, while in the control group, symptom reduction was achieved only in 47 (14.5%) patients. Conclusion. The use of drugs with hepatoprotective effect in the form of monotherapy in groups 1 (UDCA) and 2 (ademethionine) showed a low therapeutic effect with positive dynamics of clinical and laboratory indicators of toxic hepatitis activity. The use of combined treatment in group 3 (UDCA and ademethionine) demonstrated the maximum therapeutic effect, pronounced positive dynamics in the form of normalization of clinical and laboratory indicators of toxic hepatitis activity.

Aim. To assess the effect of depressive disorder (DD) on the clinical presentation of coronary artery disease (CAD) and five-year survival rate of patients with chronic CAD.Materials and methods. The study included 79 patients with functional class II–III exertional angina who experienced myocardial infarction more than 6 months before. The patients were divided into two groups: group 1 (n = 45) consisted of patients with CAD and depression and group 2 (n = 34) encompassed patients with CAD without depression. The clinical presentation of CAD was assessed by the results of filling out the angina pectoris self-control diary and exertion tests. The presence and severity of DD were determined using psychometric scales, such as Hospital Anxiety and Depression Scale (HADS) and Beck Depression Inventory (BDI), and verified by the psychiatrist. Information about five-year survival was obtained via telephone interviews with the patients and their relatives.Results. Patients with CAD and DD were characterized by more frequent episodes of angina pectoris during a week (10 [8; 14] vs 6 [4; 7], p = 0.000004), an increased demand for nitroglycerin (4 [0; 10] tablets vs 0 [0; 4] tablets, p = 0.001), and lower exercise tolerance (50 [25; 75] W vs 75 [50; 75] W (p = 0.06), 350 [250; 400] meters vs 435 [350; 500] meters (p = 0.01) than CAD patients without DD. The five-year survival rate was significantly lower in group 1 than in group 2 (69 [62; 72] vs 71 [68; 72] months (p = 0.04)), 35 (77.8%) vs 32 (94.1%) patients survived. In group 1, a greater number of deaths from cardiovascular accidents (10 (22.2%) vs 2 (5.9%)) was noted (log-rank test, p = 0.03).Conclusion. In patients with CAD, associated depression results in aggravation of the clinical course of CAD and poor disease prognosis, which requires timely diagnosis and treatment of DD.

Aim. To systematize data on the prevalence of the combination of functional dyspepsia (FD) and irritable bowel syndrome (IBS) using the Rome IIIIV Criteria. Materials and methods. A search in electronic databases MEDLINE/PubMed, EMBASE, and Cochrane was conducted. The depth of search was 17 years (from January 2006 to May 2022). Original publications from peer-reviewed periodicals that applied the Rome IIIIV Criteria for diagnosis of FD and IBS in an adult patient population with detailed descriptive statistics to allow the resulting data to be included in the meta-analysis were selected for final analysis. Results. The final analysis included 38 studies involving 17,993 patients with FD and 15,883 patients with IBS. In the overall pool of studies using the Rome IIIIV Criteria, the pooled prevalence of FD in patients with IBS was 34.625% (95% confidence interval [CI] 28.15941.390), and the pooled prevalence of IBS in patients with FD was 37.549% (95% [CI] 31.51143.787). A random-effects model was used in the analyses since significant heterogeneity between results was found (p0.0001; I298%). Using the Rome III Criteria, the pooled prevalence of FD in patients with IBS was 31.993% (95% CI 26.13538.150; I2=98.17%), while the prevalence of IBS in patients with FD was 34.694% (95% [CI] 29.31940.273; I2=97,89%). An analysis of papers using the Rome IV Criteria demonstrated that the pooled prevalence of FD in patients with IBS was 42.614% (95% CI 18.58868.675; I2=98.97%), and the prevalence of IBS in patients with FD was 50.444% (95% CI 37.95662.904; I2=94,39%). Conclusion. This meta-analysis demonstrated that the prevalence of the combination of FD and IBS identified using the Rome IIIIV Criteria is high and is reported in approximately 1 in 3 patients with the functional gastrointestinal disorders concerned. The prevalence of a combination of FD and IBS identified using the Rome IV Criteria is at least 10% higher than that using the Rome III Criteria.

Twenty-four scientists met for the annual Auxological conference held at Krobielowice castle, Poland, to discuss the diverse influences of the environment and of social behavior on growth following last year’s focus on growth and public health concerns (Hermanussen et al., 2022b). Growth and final body size exhibit marked plastic responses to ecological conditions. Among the shortest are the pygmoid people of Rampasasa, Flores, Indonesia, who still live under most secluded insular conditions. Genetics and nutrition are usually considered responsible for the poor growth in many parts of this world, but evidence is accumulating on the prominent impact of social embedding on child growth. Secular trends not only in the growth of height, but also in body proportions, accompany the secular changes in the social, economic and political conditions, with major influences on the emotional and educational circumstances under which the children grow up (Bogin, 2021). Aspects of developmental tempo and aspects of sports were discussed, and the impact of migration by the example of women from Bangladesh who grew up in the UK. Child growth was considered in particular from the point of view of strategic adjustments of individual size within the network of its social group. Theoretical considerations on network characteristics were presented and related to the evolutionary conservation of growth regulating hypothalamic neuropeptides that have been shown to link behavior and physical growth in the vertebrate species. New statistical approaches were presented for the evaluation of short term growth measurements that permit monitoring child growth at intervals of a few days and weeks.

Abstract Background It is poorly described how often headache attributed to stroke continues for more than 3 months, i.e. fulfils the criteria for persistent headache attributed to ischemic stroke. Our aims were: 1) to determine the incidence of persistent headache attributed to past first-ever ischemic stroke (International headache society categories 6.1.1.2); 2) to describe their characteristics and acute treatment; 3) to analyse the prevalence of medication overuse headache in patients with persistent headache after stroke; 4) to evaluate factors associated with the development of persistent headache after stroke. Methods The study population consisted of 550 patients (mean age 63.1, 54% males) with first-ever ischemic stroke, among them 529 patients were followed up at least three months after stroke. Standardized semi-structured interview forms were used to evaluate these headaches during professional face-to-face interviews at stroke onset and telephone interviews at 3 months. Results At three months, 61 patients (30 women and 31 men, the mean age 60.0) of 529 (11.5%) follow-up patients had a headache after stroke: 34 had a new type of headache, 21 had a headache with altered characteristics and 6 patients had a headache without any changes. Therefore 55 (10.4%) patients had a persistent headache attributed to ischemic stroke. Their clinical features included: less severity of accompanying symptoms, slowly decreasing frequency and development of medication overuse headache in one-third of the patients. The following factors were associated with these headaches: lack of sleep (29.1%, p = 0.009; OR 2.3; 95% CI 1.2–4.3), infarct in cerebellum (18.2%, p = 0.003; OR 3.0; 95% CI 1.4–6.6), stroke of undetermined etiology (50.9%, p = 0.003; OR 2.3; 95% CI 1.3–4.1), less than 8 points by NIHSS score (90.9%, p = 0.007; OR 3.4; 95% CI 1.4–8.6) and low prevalence of large-artery atherosclerosis (12.7%, p = 0.006; OR 0.3; 95% CI 0.2–0.80). Conclusion Persistent headache attributed to ischemic stroke is not rare and frequently leads to medication overuse. The problem is often neglected because of other serious consequences of stroke but actually, it has a considerable impact on quality of life. It should be a focus of interest in the follow-up of stroke patients.

Background. The development of periodontitis is strongly linked with both periodontopathogenic microflora and antioxidant-proxidant system disorders, which determines the need for the combined use of antimicrobial and antioxidant agents.Objectives. A comparative evaluation of the antioxidant-prooxidant system of red blood cells in rats with experimental periodontitis against the background of the traditional drug therapy and its combination with Soderm®-Forte and new injectable form of Rexod®.Methods. The authors conducted a comparative study of the effect of traditional drug therapy (TDT) and its combination with Soderm®-Forte gel containing silver nanoparticles, recombinant human superoxide dismutase (Rexod®) and new injectable form (NIF) of Rexod® on the condition of the antioxidant-prooxidant system of red blood cells in rats with experimental periodontitis (EP). The experiments were performed on Wistar male rats of 210–230 g. EP was induced by ligature method. The rats were randomly divided into 5 comparable groups of 12 animals: group 1 — with intact periodontium; group 2 — with EP; group 3 — with EP, where TDT was used, including oral irrigation with chlorhexedine (0.05% solution) and application of Septo-Pack dento-gingival dressing; group 4 — with EP, TDT and Soderm®-Forte gel (applied into the periodontal pockets of the lower incisors); group 5 — with EP, TDT in combination with Soderm®-Forte gel and NIF of Rexod®, which was injected intraperitoneally at a dose of 8000 U/kg. Treatment of rats with EP (groups 3–5) was carried out for 12 days. The observation period for all animals lasted 42 days. The biochemical tests and the antioxidant-prooxidant index were used to assess the condition of antioxidant-prooxidant system. Statistical analysis of the obtained results was carried out with parametric and non-parametric methods of Microsoft Excel (Microsoft, USA), Analysis package and AtteStat, as well as Statistica 8.0 (StatSoft, USA) software.Results. The application of TDT against the developed EP caused a moderate positive correction of the indicators of Antioxidant protection system (APS). The enrichment of TDT for the EP animals with Soderm®-Forte and especially Soderm®-Forte in combination with NIF of Rexod® to enhance the APS potential caused more significant positive dynamics of the balance in the antioxidant-prooxidant system compared to TDT.Conclusion. The combination of TDT with Soderm®-Forte and NIF of Rexod® has the most significant positive corrective effect on the condition of antioxidant-prooxidant system of red blood cells in rats with EP in comparison with the complex of TDT with Soderm®-Forte and TDT used separately.

There is a growing demand by the civil society for relevant information on the environment quality and related health risks. The state should be able to satisfy this demand and this makes the present research truly vital. It concentrates on correlating expert and non-expert opinions expressed when perceiving risk quantification. Our goal was to answer two following questions: 1) How does an average unprofessional person quantify a probability and severity when he or she hears certain verbal expressions that denominate them? 2) How can we possibly identify the assessment of health risks associated with environmental pollution factors given by the population in general or specific social groups? To find answers to these questions, we applied quantitative methods for data collection and analysis. The first stage involved collecting data on subjective correlation of a verbal probability scale with its numeric expression among people living in industrial cities. The second stage focused on testing the methodology for studying assessments of health risks associated with ambient air pollution given by the population/social groups. This methodology relied on the results obtained at the previous stage. We established that only 70 % of people actually correlated words with figures. We determined that experts tended to rate probabilities approximately by 10 % higher than “average people” did when it came down to such words as “Virtually certain” and “Very likely”. Such words as “Likely”, “Similarly likely” and “Unlikely” were also rated differently but with a smaller gap between the opinions. The study also provides a method for determining the public assessment of health associated with ambient air pollution. The research results give an opportunity to solve a practical task related to informing the population about health risks and to overcome a so-called language barrier between experts and ordinary people. For example, messages aimed for decision-makers can be adapted considering all the identified perception peculiarities.

Recent studies at the interface between psychiatry and neuroscience demonstrate a trend towards the investigation of single significant clinical characteristics of mental disorders in contrast to the analysis of a mental disorder as a homogeneous nosological unit. Thus, a large body of studies is focused on auditory verbal hallucinations (AVH) in schizophrenia, which are one of the core positive symptoms of the disorder and an important diagnostic criterion. Nevertheless, the neuropsychological and neurophysiological mechanisms of AVH in patients with schizophrenia remain debatable. In this paper, we will review the main neurocognitive models of AVH in schizophrenia, including models of intrusive cognitions and poor inhibitory control, a model of attentional shift to inner auditory stimuli and an inability to reallocate its resources, a model of expectation maximization, a model of working memory deficit, a model of poor source-monitoring, models of AVH within cultural-historical approach, and a model of impaired verbal self-monitoring in inner speech. The results of several neuroimaging and neurophysiological studies relevant to the models are also highlighted. We conclude that schizophrenia patients with AVH demonstrate deficits in executive functions and language, or rather a poor cross-functional interaction between them.

Aim. To determine the differences in self-assessment of social functioning by patients with chronic coronary artery disease (CAD), depending on the presence of comorbid affective disorders (ADs).Materials and methods. Using the Social Adaptation Self-Evaluation Scale (SASS), which makes it possible to assess the degree of social functioning and satisfaction with various aspects of social life, we studied the features of the social functioning of heart hospital patients with chronic CAD with (n = 248) and without AD (n = 291). In 290 patients (average age 56.6 ± 6.7 years) with chronic CAD, chronic ADs (45%) were revealed; depressive episodes (DEs) were diagnosed for the first time in 24% of patients, and 24.5% of patients had recurrent DEs. Bipolar disorder was found in 6.5% of cases. Qualitative and quantitative parameters were investigated using the Mann – Whitney U test and Student’s t-test. To assess the frequencies, the Pearson’s chi-squared test was used.Results. The mean total SASS score in the patients with chronic CAD with AD corresponded to difficult social adaptation (33.7 [29.5; 39]), while the patients without AD had good social adaptation score of 40.8 ± 6.3 (p < 0.05). In the group without AD, patients with normal social adaptation prevailed (n = 215; 73.8%), while patients with AD more often had difficulties with social adaptation (n = 148; 59.7%). In the CAD patients, depending on the presence of AD, the frequency of disturbances in various spheres of social adaptation differed: employment, interest in and pleasure from activities, disposition of income, pleasure from and interest in seeking information, social support (p = 0.001).Conclusion. Higher frequency of pronounced impairment in social functioning in patients with chronic CAD with AD determines the need for taking this fact into consideration when planning rehabilitation measures in this group of patients.

Implantable cardioverter-defibrillators (ICDs) are considered to be the most beneficial in preventing sudden cardiac death (SCD), especially in patients with reduced left ventricular ejection fraction (LVEF). However, major large-scale randomized clinical trials on ICD effectiveness were conducted 20 years ago and do not reflect current realities. Modern ICDs and methods for treating heart failure have drastically improved. New clinical reality requires reconsideration of approaches to determining the risk of SCD and indications for ICD, personalization of device selection and programming, and identification of barriers that prevent ubiquitous use of the method in real clinical practice.The article reviews the available evidence base on the use of ICDs, current clinical guidelines, complications following the device implantation, and any difficulties associated with ICD application in routine clinical practice.

Interferon beta preparations have demonstrated efficacy in the treatment of multiple sclerosis. One of the most important quality attributes that support efficacy and safety of interferon beta preparations is specific antiviral activity. Interferon beta activity is determined by the biological test method which can lead to an erroneous final result due to the system uncertainties that contribute to the overall uncertainty. Accurate assessment of specific activity plays an important role in adequate determination of the product’s therapeutic dose, therefore the test method standardisation and validation are of particular relevance. The aim of the study was to validate a test procedure for assessing specific activity of human recombinant interferon beta preparations, using various cell/virus combinations, as illustrated by the example of Infibeta®. Materials and methods: WISH, Vero, A-549, and MDBK cells in combination with mouse encephalomyocarditis virus were used in the study. The testing was performed using the biological test method based on the interferon ability to suppress virus-induced cytopathic effects in cell cultures. The results were processed using methods of mathematical statistics and the GraphPadPrism, Statistical 2/0 software package. Results: the paper compares the results of specific activity determination of Infibeta® (interferon beta-1b) using various cell/virus combinations. The dose-response curves were used to compare the test results. It was demonstrated that all the tested cell lines could be used in the biological test procedure for determination of interferon beta specific activity. However, the best results were obtained with A-549, WISH cells in combination with mouse encephalomyocarditis virus. The following validation characteristics were determined in the cell/virus systems: specificity, linearity, precision, and robustness. Conclusions: the study validated the test procedure that enables measurement of interferon beta specific activity in the range of 4.8–11.2 IU/mL at a satisfactory accuracy level, which guarantees reliable test results. The study demonstrated robustness, intermediate precision, and reproducibility of the test procedure.

Relevance. The development of medical science has made it easier for clinicians to diagnose specific diseases, often leading to the reduction of traditional diagnostic methods, including differential diagnosis. As a result, there is an increase in medical errors in diagnosis, the choice of treatment tactics, including in cases with the development of an unfavorable outcome. The aim of the study was to identify typical errors in the differential diagnosis of diseases in cases with a fatal outcome in the departments of both therapeutic and surgical profiles. Materials and Methods. At the first stage of the retrospective cohort study, fatal cases were analyzed for the correctness of the final post-mortem clinical diagnosis and the results of its comparison with the pathoanatomical diagnosis based on the results of the examination of the quality of medical care in compulsory health insurance. Errors in the formulation of the post-mortem clinical diagnosis were identified, and their causes were determined. At the second stage, the scenario method determines three variants of risk realization in the case of divergence of the final clinical and pathoanatomical diagnoses, with an assessment of the frequency of risk variants realization in the surgical and therapeutic profiles . Results and Discussion. When analyzing cases of fatal outcomes with a discrepancy between the final clinical and pathoanatomical diagnoses, the main errors in the formulation of the final clinical diagnosis were identified. In the first variant of risk realization, the reason for the discrepancy is the incorrect formulation of the final post-mortem diagnosis. In the case of the second scenario, violations relate to incorrect diagnostic tactics when a new disease or exacerbation of a chronic disease occurs. In the third scenario, violations are associated with incorrect differential diagnosis: the initial restriction of the range of nosologies for diagnostic search. Conclusion. Typical violations of diagnosis and differential diagnosis leading to a discrepancy between the final clinical and pathoanatomical diagnoses are identified. As part of the provision of medical care in surgical specialties, the second scenario is more often identified: incorrect diagnostic tactics when a new disease appears or a chronic disease worsens. When providing medical care in therapeutic specialties, violations are more often detected in the third scenario: incorrect differential diagnosis, initial restriction of the range of nosologies for diagnostic search. The second and third scenarios create legal risks for the doctor and the medical organization when evaluated by the relevant authorities.

Abstract Background A fraction of patients referred for complex molecular profiling of biopsied tumors may harbor germline variants in genes associated with the development of hereditary cancer syndromes (HCS). Neither the bioinformatic analysis nor the reporting of such incidental germline findings are standardized. Methods Data from Next-Generation Sequencing (NGS) of biopsied tumor samples referred for complex molecular profiling were analyzed for germline variants in HCS-associated genes. Analysis of variant origin was performed employing bioinformatic algorithms followed by manual curation. When possible, the origin of the variant was validated by Sanger sequencing of the sample of normal tissue. The variants’ pathogenicity was assessed according to ACMG/AMP. Results Tumors were sampled from 183 patients (Males: 75 [41.0%]; Females: 108 [59.0%]; mean [SD] age, 57.7 [13.3] years) and analysed by targeted NGS. The most common tumor types were colorectal (19%), pancreatic (13%), and lung cancer (10%). A total of 56 sequence variants in genes associated with HCS were detected in 40 patients. Of them, 17 variants found in 14 patients were predicted to be of germline origin, with 6 variants interpreted as pathogenic (PV) or likely pathogenic (LPV), and 9 as variants of uncertain significance (VUS). For the 41 out of 42 (97%) missense variants in HCS-associated genes, the results of computational prediction of variant origin were concordant with that of experimental examination. We estimate that Sanger sequencing of a sample of normal tissue would be required for ~ 1–7% of the total assessed cases with PV or LPV, when necessity to follow with genetic counselling referral in ~ 2–15% of total assessed cases (PV, LPV or VUS found in HCS genes). Conclusion Incidental findings of pathogenic germline variants are common in data from cancer patients referred for complex molecular profiling. We propose an algorithm for the management of patients with newly detected variants in genes associated with HCS.

Abstract Background Defining the relationship between a headache and stroke is essential. The current diagnostic criteria of the ICHD-3 for acute headache attributed to ischemic stroke are based primarily on the opinion of experts rather than on published clinical evidence based on extensive case-control studies in patients with first-ever stroke. Diagnostic criteria for sentinel headache before ischemic stroke do not exist. The present study aimed to develop explicit diagnostic criteria for headache attributed to ischemic stroke and for sentinel headache. Methods This prospective case-control study included 550 patients (mean age 63.1, 54% males) with first-ever ischemic stroke and 192 control patients (mean age 58.7, 36% males) admitted to the emergency room without any acute neurological deficits or severe disorders. Standardized semi-structured interview forms were used to evaluate past and present headaches during face-to-face interviews by a neurologist on admission to the emergency room in both groups of patients. All headaches were diagnosed according to the ICHD-3. We tabulated the onset of different headaches before a first-ever ischemic stroke and at the time of onset of stroke. We divided them into three groups: a new type of headache, the previous headache with altered characteristics and previous unaltered headaches. The same was done for headaches in control patients within one week before admission to the hospital and at the time of entry. These data were used to create and test diagnostic criteria for acute headache attributed to stroke and sentinel headache. Results Our previous studies showed that headache at onset of ischemic stroke was present in 82 (14.9%) of 550 patients, and 81 (14.7%) patients had sentinel headache within the last week before a stroke. Only 60% of the headaches at stroke onset fulfilled the diagnostic criteria of ICHD-3. Therefore, we proposed alternative criteria with a sensitivity of 100% and specificity of 97%. Besides, we developed diagnostic criteria for sentinel headache for the first time with a specificity of 98% and a sensitivity of 100%. Conclusions We suggest alternative diagnostic criteria for acute headache attributed to ischemic stroke and new diagnostic criteria for sentinel headache with high sensitivity and specificity.

The presented clinical observation reflects the difficulties of differential diagnosis of progressive kidney damage in a patient with sarcoidosis who has undergone a new coronavirus infection. The differential circle included interstitial nephritis as an exacerbation of the underlying disease, acute drug-induced kidney injury, acute glomerulonephritis. Nephrobiopsy confirmed the diagnosis of acute sarcoid tubulointerstitial nephritis with acute tubular necrosis. Timely administration of corticosteroids led to the control of the sarcoidosis process, restoration of kidney function.

At an international online expert meeting held on September 16, 2021, the results of the empagliflozin research program EMPA-REG Outcome, EMPEROR-Reduced and EMPEROR-Preserved were reviewed. We analyzed cardiovascular and renal outcomes during the treatment with empagliflozin in patients with chronic heart failure, regardless of the presence of type 2 diabetes mellitus. The positive results of the EMPEROR-Preserved study are updated and their significance for clinical practice is discussed. Several proposals have been adopted that will accelerate the introduction of empagliflozin therapy into practice in patients with heart failure and overcome clinical inertia.

Abstract Mesoproterozoic period included several global tectonic events like break-up of Nuna and formation of Rodinia. However, although Siberia is a significant piece of both supercontinents, Mesoproterozoic time is marked by quiescence of magmatic and tectonic activity in it. We report here a mafic dyke (named Gornostakh dyke) in the southeastern Siberian Craton dated at 1419 ± 32 Ma by LA-ICPMS U–Pb geochronology of apatite. The dyke has tholeiitic compositions with high MgO and alkaline content, low-Ti, and arc-like trace element pattern. Due to the absence of subduction tectonics in the study area, geochemical data could be attributed to a significant contribution from metasomatically enriched subcontinental lithospheric mantle previously modified by subduction processes. That kind of composition is common for low-Ti dykes of intraplate flood basalt provinces similar to, for example, Permian–Triassic Siberian large igneous province (LIP). Paleogeographic reconstructions suggest that Siberia was connected to Laurentia and Baltica and their reconfiguration interrupts a prolonged tectonic quiescence in the Siberian Craton from ca. 1.88 Ga reflecting a transition from Nuna to Rodinia configuration. The mafic magmatism on 1419 Ma on the southeastern margin of the Siberian Craton together with coeval extensional tectonics observed in the structure of the Sette-Daban ridge proposes a hypothetical LIP which may be a direct consequence of the beginning of this transition.

Objectives the in-depth analysis of the informational and legal base for organisation of remote medical care for patients with diabetes mellitus in the context of the COVID-19 pandemic. Material and methods. Official memoranda of the WHO and the International Labour Organization (ILO), decisions of the Government of the Russian Federation and foreign countries on the use of remote telemedicine counseling in the context of the COVID-19 pandemic were reviewed and analysed. Results.After reviewing the results of remote telemedicine counseling to provide specialized medical care to patients with diabetes during COVID-19 pandemic on various virtual platforms, we defined the factors limiting the widespread use of this technology. We collected metadata of the results of the original experience of remote consultation of patients with endocrine pathology using the automated workplace of an endocrinologist (AWPE). Conclusion.In the context of the COVID-19 pandemic, the development and implementation of new promising forms of outpatient work using digital telecommunication technologies is particularly relevant. The use of remote access telemedicine consulting techniques via Automated endocrinologist's workplace for patients with endocrine pathology during the period of self-isolation showed its effectiveness in a pilot study. Its widespread introduction into outpatient practice will not only significantly increase the availability of medical care for patients with diabetes, but also minimize the risk of infection with a new coronavirus for doctors.

Abstract The pandemic infectious disease (Covid-19) caused by the coronavirus (SARS-CoV2) is spreading rapidly around the world. Covid-19 does an irreparable harm to the health and life of people. It also has a negative financial impact on the economies of most countries of the world. In this regard, the issue of creating drugs aimed at combating this disease is especially acute. In this work, molecular docking was used to study the docking of 23 compounds with QRF3a SARS-CoV2. The performed in silico modeling made it possible to identify leading compounds capable of exerting a potential inhibitory and virucidal effect. The leading compounds include chlorin (a drug used in PDT), iron(III)protoporphyrin (endogenous porphyrin), and tetraanthraquinone porphyrazine (an exogenous substance). Having taken into consideration the localization of ligands in the QRF3a SARS-CoV2, we have made an assumption about their influence on the pathogenesis of Covid-19. The interaction of chlorin, iron(III)protoporphyrin and protoporphyrin with the viral protein ORF3a were studied by fluorescence and UV–Vis spectroscopy. The obtained experimental results confirm the data of molecular docking. The results showed that a viral protein binds to endogenous porphyrins and chlorins, moreover, chlorin is a competitive ligand for endogenous porphyrins. Chlorin should be considered as a promising drug for repurposing.

Personalized therapy is starting to play an increasing role in modern approaches to the treatment of oncological diseases. The previously existing uniform standard for each malignant disease is expanded with new options and treatment possibilities, depending on each specific clinical situation. That increases the effectiveness of therapy and helps to control the disease. A separate niche in the individual approach to anti-tumor treatment is occupied by targeted therapy of malignancies. There are a lot of mutations that can lead to the emergence of malignant neoplasms. So of all that multitude of choices the individual approach to a patient helps to select the mutations that are most likely to be found in a given patient. The research in the area of the c-MET mutation has allowed it to occupy its niche as a therapeutic target. The identification of this mutation is not included in the routine set of analyses performed for a patient with diagnosed lung adenocarcinoma. But expanding the panel of molecular testing would increase the detectability of this mutation and, as a result, improve the quality of treatment for this category of patients. This clinical case describes the experience of treatment of an elderly patient with lung adenocarcinoma, in whose tumor tissue a MET mutation was detected.

Введение. Анализ литературы показал, что ангиогенез играет ключевую роль в прогрессировании фиброза печени. Однако имеющиеся научные сообщения о морфологических изменениях сосудистой системы печени недостаточны и противоречивы. Цель работы – исследование морфологических изменений сосудистой системы печени крыс под воздействием тиоацетамида. Материал и методы. Фиброз и цирроз печени у крыс Wistar индуцировали тиоацетамидом в дозе 200 мг/кг веса животного в течение 17 недель. Для исследования морфологических изменений использовали классический и иммуногистохимический методы окраски гистологических препаратов. Микроскопический анализ проводили с использованием микроскопа OLYMPUS BX51 и программ анализа изображений ImageScope Color и cellSens Standard. Результаты. Внутрижелудочное введение животным раствора тиоацетамида приводит к плавному нарастанию прогрессии патологических изменений и позволяет отследить все стадии развития цирроза и морфологическую перестройку сосудистой системы печени. На протяжении всего эксперимента происходили интенсивная капилляризация синусоидов паренхимы, неоангиогенез в портальных трактах и соединительнотканных септах, который проявлялся формированием множества венул и мелких вен; увеличение площади междольковых вен, местами достигших гигантских размеров. Выявлены три морфологических фенотипа CD34-позитивных клеток: в междольковых артериях, междольковых, центральных и поддольковых венах данные клетки имели вытянутую форму и палочковидное темноокрашенное ядро; при трансформации фиброза печени в цирроз в синусоидах (ближе к периферии отдельных ложных узелков) отмечались CD34-позитивные клетки вытянутой формы со светлыми округло-вытянутыми ядрами; в соединительной ткани около печёночных триад, в соединительнотканных септах среди клеток инфильтрата и между резко увеличенным количеством желчных протоков наблюдались клетки округлой формы с темноокрашенными ядрами. Выводы. Установленные сложные фенотипические изменения синусоидальных эндотелиальных клеток доказывают тесную связь фиброгенеза с неоангиогенезом и, вероятно, они играют ведущую роль в развитии фиброза и перестройке венозной системы портальной вены.

Abstract In countries where headache services exist at all, their focus is usually on specialist (tertiary) care. This is clinically and economically inappropriate: most headache disorders can effectively and more efficiently (and at lower cost) be treated in educationally supported primary care. At the same time, compartmentalizing divisions between primary, secondary and tertiary care in many health-care systems create multiple inefficiencies, confronting patients attempting to navigate these levels (the “patient journey”) with perplexing obstacles. High demand for headache care, estimated here in a needs-assessment exercise, is the biggest of the challenges to reform. It is also the principal reason why reform is necessary. The structured headache services model presented here by experts from all world regions on behalf of the Global Campaign against Headache is the suggested health-care solution to headache. It develops and refines previous proposals, responding to the challenge of high demand by basing headache services in primary care, with two supporting arguments. First, only primary care can deliver headache services equitably to the large numbers of people needing it. Second, with educational supports, they can do so effectively to most of these people. The model calls for vertical integration between care levels (primary, secondary and tertiary), and protection of the more advanced levels for the minority of patients who need them. At the same time, it is amenable to horizontal integration with other care services. It is adaptable according to the broader national or regional health services in which headache services should be embedded. It is, according to evidence and argument presented, an efficient and cost-effective model, but these are claims to be tested in formal economic analyses.

Aim. To identify the presence and the correction method of decreased heart rate variability (HRV) in patients with chronic coronary artery disease (CAD) and comorbid depressive disorders (DD).Materials and methods. 79 patients with CAD (with class II–III angina pectoris and myocardial infarction that occurred more than 6 months ago) were divided into two groups. The first group included 50 CAD patients with depression, and the second – 29 CAD patients without depression. 17 patients received agomelatine (1st subgroup), 12 patients received fluvoxamine and fluoxetine (2nd subgroup), and 21 patients refused to take antidepressants (3rd subgroup). Initially and after 6 months, the HRV parameters were evaluated using the SCHILLER MT-200 Holter-ECG apparatus (Switzerland).Results. A significant decrease in HRV was revealed in the patients with depression compared to the patients without it: SDNN (96 [83; 117] ms vs. 110 [98; 127] ms; p = 0.02), SDANN (80.5 [67; 94] ms vs. 91 [79; 102] ms; p = 0.03), SDNNindex (46.5 [38; 56] ms vs. 55 [48; 66] ms; p = 0.006), rMSSD (29 [23; 38] ms vs. 33 [29; 45] ms; p = 0.04), pNN50% (3.9 [2.4; 5,7] vs. 5.7 [2.9; 12.6]; p = 0.03). Initially, the 1st, 2nd, and 3rd subgroups did not differ in all HRV parameters. Against the background of antidepressant therapy, there were significant differences between the 2nd and 3rd subgroups in SDNN (110 [96; 140] ms vs. 85.5 [75; 103] ms; p = 0.008), SDANN (93.7 ± 22.9 ms vs. 72.7 ± 21.4 ms; p = 0.02), SDNNindex (55.8 ± 16.4 ms vs. 42.4 ± 10.8 ms; p = 0.01) and pNN50% (7.8 ± 6.7 vs. 3.6 ± 1.8; p = 0.02), as well as between the 1st and 3rd subgroups (SDANN (93.6 ± 28.5 ms vs. 72.7 ± 21.4 ms; p = 0.03), rMSSD (36.5 [28.5; 51] ms vs. 26.5 [25; 32] ms; p = 0.02)).Conclusion. In patients with CAD with comorbid DD, significant impairment of heart rhythm regulation occurs due to a pronounced decrease in HRV, which can seriously affect the course and prognosis of CAD. Prescribing modern antidepressants can be used as a method of correcting autonomic dysfunction in patients with CAD with comorbid depression.

Seventeen scientists met for this year’s conference on Auxology held at Krobielowice castle, Poland, to discuss growth and public health concerns. The regulation of growth is complex and besides metabolic and endocrine components including hypothalamic releasing factors, growth hormone and multiple downstream effectors, comprises the full spectrum of the psychosocial, economic and emotional environment including signaling dominance, competence, prestige, or subordination and indulgence, all of this being sensitive to urban or rural lifestyle, the political climate and with marked plasticity throughout history. New statistical techniques (St. Nicolas House Analysis) are presented for analyzing anthropometric variables for public health concerns. The impact of spatial differences on developmental tempo, growth in height, and the prevalence of childhood obesity are discussed as well as the impact of social mobility on obesity, and the benefits of the biopsychosocial status when getting along with socio-economic disasters and the COVID-19 pandemic.

Abstract Two millets, Panicum miliaceum and Setaria italica, were domesticated in northern China, around 6000 BC. Although its oldest evidence is in Asia, possible independent domestication of these species in the Caucasus has often been proposed. To verify this hypothesis, a multiproxy research program (Orimil) was designed to detect the first evidence of millet in this region. It included a critical review of the occurrence of archaeological millet in the Caucasus, up to Antiquity; isotopic analyses of human and animal bones and charred grains; and radiocarbon dating of millet grains from archaeological contexts dated from the Early Bronze Age (3500–2500 BC) to the 1st Century BC. The results show that these two cereals were cultivated during the Middle Bronze Age (MBA), around 2000–1800 BC, especially Setaria italica which is the most ancient millet found in Georgia. Isotopic analyses also show a significant enrichment in 13C in human and animal tissues, indicating an increasing C4 plants consumption at the same period. More broadly, our results assert that millet was not present in the Caucasus in the Neolithic period. Its arrival in the region, based on existing data in Eurasia, was from the south, without excluding a possible local domestication of Setaria italica.

Abstract The picturesque and high conservation value thermal landscapes of the Valley of Geysers feature endothermal (heated by endogenous fluids) soils which support endangered and unique species. However, such soils have not been distinguished as a separate taxon within most classification systems. In this study, we described the soil morphology at macro-, meso- and micro-scales, chemistry, mineralogy and vegetation of these landscapes as they are affected by the steam-heated acid-sulfate waters. The studied catenary sequence from exothermal (non-heated) to endothermal soils was characterized by decreasing contents of soil organic carbon, sand fraction, essential nutrients (Ca, K, Mg, Mn and Si), increasing soil acidity, amounts of fine particle-size fractions and contents of trace elements (Al, As, Co, Cr, Cu, Fe, Pb, Ti and V) as well as the development of sodium-sulfate salinity, kaolinization and ferrugination. In phytocenoses supported by endothermal soils, species of order Rosales and Asparagales were overrepresented among obligate and facultative thermophytes respectively, and species of order Poales were underrepresented among facultative thermophytes in relation to the flora of the Valley of Geysers. Phytocenoses on the non-heated Andosols were enriched in Polypodiopsida species. The results of our comparative analysis of the thermally-induced variability in the soils and vegetation contribute to the general understanding of mineralogical, bio-abiotic and biological systems affected by steam-heated acid-sulfate waters. We hope that our findings will provide a basis for future transdisciplinary studies of the influence of steam-heated waters of a hot spring on the thermal landscapes.

Introduction. Functional dyspepsia (FD) and irritable bowel syndrome (IBS) overlap is an adverse clinical situation, as patients with this syndrome have more severe clinical manifestations resulting in significant reductions in quality of life. For now, there are no meta-analytical papers that would summarize the frequency of FD – IBS overlap using the revised Rome IV criteria. Objective. To organize data on the prevalence of FD – IBS overlap using the revised Rome IV criteria.Materials and methods. A search for studies was conducted in MEDLINE / PubMed, EMBASE, Cochrane electronic databases. The search depth was 6 years (from January 2016 to February 2021). The final analysis included original publications from peerreviewed periodicals that used the revised Rome IV criteria as a method for diagnosing FD and IBS in the adult population with detailed descriptive statistics allowing to include resulting data in the meta-analysis.Results and discussion. The final analysis included 6 studies involving 1,180 patients with PD and 600 patients with IBS. The generalized prevalence of IBS in patients with PD was 41.511% (95% CI: 22.203–62.288). The analysis was undertaken by using a random-effects model, as there was significant heterogeneity among results (p < 0.0001; I2 = 94.28%). The generalized prevalence of PD in patients with IBS was 38.791% (95% CI: 9.438–73.710). The analysis was undertaken by using a random-effects model, as there was significant heterogeneity among results (p < 0.0001; I2 = 99.25%).Сonclusion. The complete meta-analysis showed that the frequency of FD - IBS overlap using the revised Rome IV criteria is quite high and accounts for about 40%. At the same time, further large studies of more homogeneous structure are needed to verify these results and study the potential pathogenetic relationship between PD and IBS.

Aim. To determine gender differences in self-reported social functioning of patients with comorbidity of affective disorders (ADs) and chronic coronary artery disease.Materials and methods. Self-reported social functioning of 248 cardiological patients (194 men (78.2%) and 54 women (21.8%)) with chronic coronary artery disease (CAD) and ADs was studied using the Social Adaptation Self-evaluation Scale (SASS). The mean age of patients with chronic CAD in men was (57.2 ± 6.5) years, and in women (59.3 ± 7.1), p = 0.04. Qualitative and quantitative indicators were investigated using the Mann – Whitney, Wilcoxon and T-test; χ2 (Pearson›s goodness-of-fit test) was used to estimate the frequencies.Results. ADs were represented by chronic mood disorders (45%), first-time depressive episodes (DEs) 24%, recurrent DEs 24.5%, as well as bipolar II disorder (BD II) 6.5%. ADs in 42.4% of patients were associated with psychosocial stressors (mainly, loss), p = 0.02. Men statistically significantly more often (37.1%, 72/194) than women (16.7%, 9/54) communicated more scarcely with others as a result of projection mechanisms, a high level of hostility, passive aggressiveness and lack of initiative, typical for patients with ADs, p = 0.003.Conclusion. The social functioning of patients with ADs and chronic coronary artery disease was complicated irrespective of gender. Women were single and bereaved of their children more often than men. Due to the low level of communication outside the family and outside of professional activity, most of the patients maintained communication mainly with the family. However, due to ADs, they were not able to feel support from familymembers and rarely initiated communication with other people (men did it statistically significantly more often than women).

Pulmonary vascular endothelium dysfunction is one of the main pathogenic factors responsible for many clinical manifestations of the severe course of COVID-19. Circulating endothelial progenitor cells (EPCs) are the endogenous regenerative reserve that maintains the integrity of the vascular endothelium and its restoration in case of damage by pathogenic factors. A decrease in the circulating EPCs is regarded as a predictor of morbidity and mortality in conditions associated with development of endothelial dysfunction, including COVID-19. The exact phenotype of progenitor cells capable of differentiating into endothelial cells has not been determined. In most laboratories antigens CD133+, CD34+, VEGFR-2+ (CD 309) or combination of these are used to identify EPCs. The process of EPCs mobilization and migration is controlled by molecular signals from immune cells located in the damage area. Stromal cell factor 1 (SDF-1), produced by the bone marrow and many other tissues, is an important chemoattractant for EPCs which express its receptors. The results of studies carried out in 2020 indicate that SARS-Cov-2 infects both hematopoietic stem cells, transforming into EPCs, and directly circulating EPCs, causing inflammatory and procoagulant reactions that complicate the COVID-19 course. There is no consensus on the mechanism of EPCs infection with coronavirus – directly through the expression of angiotensin-converting enzyme (ACE2) receptor or through an ACE2-independent mechanism. Today there is no effective therapy for COVID-19. The use of the EPCs regenerative potential, and the search for ways to enhance the EPCs mobilization from the depot, and increase their functional activity may become a promising approach to the prevention of severe complications and mortality from COVID-19.

Abstract Omniphobic and icephobic twin-scale surfaces based on the “urchin”-like fluorinated Al2O3 particles are presented. Combined effect of hierarchical topography and fluorination supplied to the surfaces omniphobic and icephobic properties. The study of the stability of the Cassie wetting state is reported. High apparent contact angles were accompanied with the low contact angle hysteresis and high stability of the Cassie air trapping wetting state. Time delay of the ice crystallization as high as $$88\pm 5$$ 88 ± 5 min was established when compared to the ice formation on flat aluminum and non-fluorinated “urchin”-like surfaces. Crystallized water droplets formed on the reported nano-structured surfaces were easily blown out by the air jet with the velocity of $$v=3.0\pm 1.0$$ v = 3.0 ± 1.0 m/s, (which is markedly lower than that common for exploitation of aircrafts and turbines). Heated “urchin”-like surfaces completely restored their omniphobic and icephobic surfaces after thawing. Qualitative analysis of water freezing is supplied.

Quality control of recombinant interferon (rIFN) products with the help of modern analytical methods, including those used for identification, is becoming increasingly relevant nowadays. Identification is especially challenging in the case of Russian rIFN products that contain not only interferon (IFN) alpha-2b, but also other active ingredients and excipients that hinder the use of physical and chemical methods. Manufacturers of such products use IFN neutralization assay with mono- and/or polyclonal antibodies for identification. The aim of the study was to assess the feasibility of using different types of antibodies in the identification test based on neutralization of IFN antiviral activity in IFN alpha-2b products containing other active ingredients and excipients in addition to IFN. Materials and methods: the following materials were used in the study: MDBK cells, vesicular stomatitis virus, samples of IFN alpha-2b products with different composition and by different manufacturers, mono- and polyclonal antibodies by different manufacturers. Identification of rINFs was carried out by a biological method based on neutralization by specific antibodies of IFN ability to suppress the cytopathic effect of the indicator virus in a cell culture using a reference standard for comparison. Results: both polyclonal and monoclonal antibodies were shown to neutralize the activity of the tested IFN alpha-2b substances. Polyclonal antibodies interact with all products containing the same active ingredients, irrespective of their composition. Monoclonal antibodies interact selectively with some products. Conclusions: polyclonal antibodies can be used for identification of any product containing IFN alpha-2b. The use of monoclonal antibodies for this purpose is limited and depends on the composition of the product.

The literature review presents novel data on the prevalence of age-related hypogonadism and its relationship with aging, its impact on the circulatory system and cardiovascular diseases. This review summarizes the methods for diagnosing age-related hypogonadism, its association with traditional cardiovascular risk factors such as dyslipidemia, insulin resistance and diabetes mellitus, obesity, arterial hypertension. The mechanisms of the possible direct effect of testosterone on endothelium and vascular tone, the role of hormone replacement therapy as a way of preventing cardiovascular diseases are discussed.

Leishmaniasis is a vector-born parasitic disease characterized by predominant cutaneous or visceral involvement with fever, hepatosplenomegaly and anemia. Leishmaniasis has relatively high prevalence in tropical and subtropical areas. Several sporadic and mostly imported cases are detected in Russian Federation. Nevertheless, some local incidents are noted in southern areas (Crimea, Dagestan). Lack of epidemiological alertness hampers confirmation of diagnosis and may lead to incorrect treatment. The article summarizes current state of knowledge in epidemiology, diagnostic approach and treatment of leishmaniasis. Particular clinical case is discussed.

Aim.To study the association of single-nucleotide polymorphismrs3025058(5а/6а) with the development of stroke in patients of the East Siberian population with cardiovascular pathology and risk factors for its development. Materials and methods.The study involved 260 patients with stroke (age [57.0; 51.062.0]) and 272 patients of the control group (age [55.0; 51.062.0]). Among the patients who underwent stroke, 157 men and 103 women. The control group included 170 men and 102 women. The examination of the main group included: collection of complaints, anamnesis, clinical examination, computed tomography of the brain, electrocardiography, echocardioscopy, ultrasound duplex scanning of the extracranial brachiocephalic arteries, 24-hour monitoring of blood pressure and heart rate, analysis of the blood coagulation system. The patients of the main group had the following cardiovascular pathology and risk factors: arterial hypertension, paroxysmal supraventricular tachycardias, dyslipidemia, atherosclerosis of extracranial brachiocephalic arteries, disorders of the hemostasis system. The control group was examined within the framework of the international project HAPIEE. Molecular genetic research was carried out by real-time PCR. Statistical processing of the material was carried out using the Statistica for Windows 7.0, Excel and SPSS 22 application software. Results.The study established statistically significant associations between the 5a/5a genotype and the 5a allele and stroke in the general group of patients, as well as in the subgroup of men, subgroups of patients with extracranial brachiocephalic arteries atherosclerosis and dyslipidemia. In the subgroup of patients with cardiac arrhythmias, statistically significant results were obtained only for allele 5a, and in the subgroup of women with stroke, subgroups of patients with arterial hypertension and hypercoagulation, no significant associations ofrs3025058(5a/6a) polymorphism with stroke were found. Conclusion.Genotype 5a/5a and allele 5a of the single-nucleotide polymorphismrs3025058(5а/6а) increase the risk of stroke in individuals from the East Siberian population, including those in the presence of such risk factors as extracranial brachiocephalic arteries atherosclerosis and dyslipidemia.

In clinical practice, acute-phase protein measurements during inflammation are usually used to monitor the activity and severity of adult-onset Still's disease (AOSD).Objective: to study the possibility of using the neutrophil-to-lymphocyte ratio (NLR) in complete blood cell count as a marker for the activity and severity of AOSD in clinical practice.Patients and methods. The investigation enrolled 48 patients (29 females and 19 males; mean age, 32.8±12.5 years) with active AOSD, who met the criteria devised by M. Yamaguchi et al. Along with standard clinical and laboratory parameters and systemic scores, NLR was calculated in complete blood cell count.Results and discussion. There was a statistically significant correlation of NLR with the level of CRP (r=0.532), ferritin (r=0.43), ESR (r=0.40), and the systemic score reflecting the severity of the disease (r=0.449), which allows NLR to be regarded as a tool that is convenient to assess the activity and severity of AOSD in clinical practice.Conclusion. The findings have shown the good sensitivity and specificity of NLR, which indicates the possibility of using the latter as an available marker for assessing the activity and severity of AOSD in clinical practice.

Chronic pelvic pain resulting from varicose veins of the small pelvis is a multidisciplinary problem. A key cause of pelvic congestion is congenital or acquired gonadal valve failure. Ultrasound and Doppler examination for chronic pelvic pain allows in most cases to diagnose pelvic varicose veins. Multispiral computed tomography or magnetic resonance imaging details the nature and extent of the pathology. Selective phlebography is considered the gold standard for diagnosing varicose veins of the small pelvis. Conservative treatment with phlebotropic drugs is prescribed for limited pelvic varicose veins. Surgical treatments include open resection and retroperitoneal and transperitoneal laparoscopic gonadal vein excision or clipping. The most effective is minimally invasive endovascular occlusion of reflux veins using spiral technologies and sclerosants. The left ovarian vein is reduced more often. The decision on bilateral embolization of blood vessels depends on the severity of changes in veins and the intensity of blood reflux. A decrease in the intensity or disappearance of pain in the pelvic area is achieved in 80–100% of cases after the procedure. Diagnosis of this condition is difficult due to the fact that the appearance of pelvic varicose veins is nonspecific and includes symptoms of surgical, urological, gynecological and other diseases of the pelvic organs.

Introduction: Surgical correction of adolescent idiopathic scoliosis is inevitably accompanied by blood loss. About 37–85% of patients undergo allogeneic transfusions associated with a risk of serious complications. Prediction of the expected blood loss volume remains a topical problem. In this regard, there is a need to clarify predictors of increased blood loss.Aim: To assess the effect of vertebrectomy on the intraoperative blood loss volume during surgical correction of adolescent idiopathic scoliosis.Materials and methods: A retrospective study included 511 adolescents who underwent posterior correction of spinal deformity. Two groups were allocated: Group I consisted of 303 patients who underwent multilevel transpedicular fixation; Group II included 208 patients who underwent multilevel transpedicular fixation combined with Smith-Peterson osteotomy.Results: Intergroup comparisons revealed significant differences in the number of transpedicular fixation levels and the volume of blood loss, which were higher in Group II. After aligning the groups by the number of transpedicular fixation levels using the Propensity Score Matching method, no statistically significant difference was observed. We derived formulas for calculating the expected blood loss volume in Groups I and II. Comparison of the formulas revealed that the formula for Group II predicted a significantly lower volume of blood loss, by 2.51%, while the formula for Group I predicted a significantly higher volume of blood loss, by 3.27%. In our opinion, application of the formula that overestimates expected intraoperative blood loss is most reasonable due to a possibility of the worst case scenario during surgery; therefore, the formula for Group I approaches a universal model for use.Conclusion: Smith-Peterson osteotomy did not affect the amount of blood loss during surgical correction of adolescent idiopathic scoliosis, considering the number of transpedicular fixation levels.

Abstract Neuromyelitis Optica (NMO) is an autoimmune disease with a higher prevalence in non-European populations. Because the Mexican population resulted from the admixture between mainly Native American and European populations, we used genome-wide microarray, HLA high-resolution typing and AQP4 gene sequencing data to analyze genetic ancestry and to seek genetic variants conferring NMO susceptibility in admixed Mexican patients. A total of 164 Mexican NMO patients and 1,208 controls were included. On average, NMO patients had a higher proportion of Native American ancestry than controls (68.1% vs 58.6%; p = 5 × 10–6). GWAS identified a HLA region associated with NMO, led by rs9272219 (OR = 2.48, P = 8 × 10–10). Class II HLA alleles HLA-DQB1*03:01, -DRB1*08:02, -DRB1*16:02, -DRB1*14:06 and -DQB1*04:02 showed the most significant associations with NMO risk. Local ancestry estimates suggest that all the NMO-associated alleles within the HLA region are of Native American origin. No novel or missense variants in the AQP4 gene were found in Mexican patients with NMO or multiple sclerosis. To our knowledge, this is the first study supporting the notion that Native American ancestry significantly contributes to NMO susceptibility in an admixed population, and is consistent with differences in NMO epidemiology in Mexico and Latin America.

Cardiovascular calcification (CVC) makes a significant contribution to the manifestation of cardiovascular complications in patients with chronic kidney disease. Early CVC markers are currently being actively studied to optimize cardio-renoprotective strategies. We performed a prospective comparative analysis of the following factors: FGF-23, a-Klotho, sclecrostin, phosphate, parathyroid hormone, the estimated glomerular filtration rate (eGFR), central systolic pressure as an independent determinant of CVC. Materials and methods. The study included 131 patients with chronic kidney disease 25D st. Serum levels of FGF-23, Klotho, and sclerostin were evaluated using the ELISA method. Vascular augmentation (stiffness) indices, central arterial pressure (using the SphygmoCor device), calcification of heart valves and the degree of aortic calcification (aortic radiography) were also investigated. The observation period was 2 years. Results. According to the Spearman correlation analysis, the percent of calcification increase and the change in Klotho level are most related. According to ROC analysis, a decrease in serum levels of Klotho by 50 units or more is a significant predictor of an increase in aortic calcification of 50% or more with a sensitivity of 86% and a specificity of 77%. Using logistic regression analysis, it was found that a serum Klotho level 632 pg/L predicts an eGFR below a median level of 48 ml/min/1.73 m2 with a sensitivity of 85.5% and a specificity of 78.5%. Wherein OR 17.477 (CI 95% 8.04637.962; p0.001). Conclusion. The factor most associated with CVC is Klotho. Decreased serum level of Klotho is a predictor of aortic calcification. In addition, the initial serum level of Klotho is a predictor of eGFR after 2 years.

Cardiac infarction is considered a disease more common for elderly people; despite that, up to 10% of all cardiac infarctions occur at a young age. Cardiac infarction has grave consequences both for mental health and future working capability of patients who had it. Approximately 15% patients who have had cardiac infarction have to face a recurrent cardiovascular event based on thrombus formation in spite of therapy. Our research goal was to assess endothelium homeostasis in patients after cardiac infarction being treated with double anti-thrombocyte therapy during out-patient rehabilitation and to reveal potential risks that could cause recurrent cardiovascular diseases. Overall, we examined 25 people aged from 18 to 45 who had cardiac infarction and were treated with invasive therapy aimed at eliminating ischemic heart disease. The therapy was emergency percutaneous coronary intervention and coronary artery stenting performed at Perm Clinical Cardiologic Clinic during a period from September 2018 to March 2019. Endothelial homeostasis was examined in 12 months after cardiac infarction. We detected that, together with conventional risk factors, young patients after cardiac infarction had apparent changes in coagulation homeostasis (shorter activated partial thromboplastin time, shorter prothrombin time, an increase in fibrinogen concentration; greater aggregative activity of thrombocytes with adenosine-diphosphate; depressed Hageman-factor-dependent fibrinolysis. Nevertheless, there was no significant difference in aggregative activity of thrombosytes with ristocetin between the test and control groups. Therefore, in 12 months after cardiac infarction, young patients still ran high risks of recurrent cardiovascular events; those risks were caused both by significant prevalence of conventional risk factors and by high thrombogenic risk that persisted in spite of relevant anti-thrombus therapy.