Search

The bivalent chemical cholera vaccine is the only drug for the prevention of cholera registered in the Russian Federation. The vaccine has been produced in glass bottles containing 210 tablets. At the same time, modern trends dictate the need to produce the drug in varying dispensing and more practical packaging for the convenience of the consumer.The aim of the work was to study the stability of the properties of the immunobiological medicinal product “Bivalent chemical cholera vaccine” with modified filling and in new primary packaging.Materials and methods. When studying the quality of bivalent chemical cholera vaccine batches, physicochemical parameters, formaldehyde content, specific activity and safety, abnormal toxicity, immunogenicity, and microbiological purity were assessed. Stability in terms of “specific activity” was evaluated using dot immunoassay.Results and discussion. As a result of this work, the use of several dispensing options and new primary packaging of cholera vaccine has been experimentally substantiated. The stability of the finished vaccine preparation has been established in the “accelerated aging” test and during long-term storage. The possibility of using dot immunoassay with a conjugate based on staphylococcal protein A, labeled with colloidal gold, to monitor the stability of cholera vaccine has been experimentally demonstrated.

Background. The main deposits of Donbass and their mineral resource potential are considered.Aim. To develop a strategy for the socio-economic development of Donbass under contemporary political and economic conditions, with a focus on the development of human capital and further integration with the Russian Federation, CIS, and friendly countries.Materials and methods. A multipronged approach was used to define the contours, directions, and stages of the socio-economic development of Donbass.Results. The conducted analysis of the current state of the mineral resource base of Donbass revealed the most significant types of mineral resources for Donbass economy. An economic estimate of the cost of mineral resources extracted in Donbass and their market demand was obtained. Various types of resources were ranked in terms of their significance for Donbass economy.Conclusion. An approach to an integrated assessment of the expenses associated with the restoration of the mineral resource base of Donbass is proposed. In this respect, priority directions of economic activities are established.

Initiation of insulin therapy with basal insulin analogues has become the standard of care for type 2 diabetes mellitus (T2DM). Timely administration of insulin allows not only to slow down the progression of type 2 diabetes, but also to reduce the frequency and severity of complications associated with it. This paper reviews the efficacy and safety of the use of the latest basal insulin analogues in type 2 diabetes from the perspective of current clinical guidelines, and also reviews updated data on the efficacy and safety of therapy by various members of the class. In this paper a review of the efficacy and safety of latest basal insulin analogues use in T2DM from the standpoint of current clinical guidelines has been carried out, and updated data on the efficacy and safety of therapy by various members of the class have been reviewed, taking into account their impact on the risk of hypoglycemia and glycemic variability. The available data indicate that insulin degludec 200 U/mL may be the drug of choice for those at high risk of developing severe forms of hypoglycemia. Since severe hypoglycemia and high glycemic variability are important risk factors for cardiovascular events and mortality, it has been shown that a differentiated approach to insulin therapy in the treatment of T2DM is currently advisable, taking into account the effect on the risk of hypoglycemia and glycemic variability.

Thrombotherapy is an important approach in treatment of various diseases associated with pathologies of the cardiovascular and human hemostasis systems. Screening for producers of modern, specific, and safe thrombolytic substances is an important task for medicine and biotechnology. The aim of this study was to characterize thrombolytic potential of seven strains of micromycete belonging to the genus Tolypocladium, which was obtained from White Sea soils. The Tolypocladium inflatum 62a strain was considered the most promising producer of thrombolytic agent activities suitable for possible use in thrombotherapy or diagnostics of hemostasis pathologies. It demonstrated a high radial growth rate and was characterized not only by a sufficiently high value of enzymatic index in media with fibrin and fibrinogen but also by the highest specificity for fibrillar proteins among all strains. The preparation obtained from it demonstrated pronounced thrombolytic effectiveness and substrate specificity.

Bladder cancer is globally considered as one of the most aggressive neoplasms. Traditionally, first-line therapy for metastatic urothelial carcinoma has remained unchanged over the past decades and has been based on combinations of cisplatin. Unfortunately, almost all patients eventually progress and die from bladder cancer, despite the initial response associated with cisplatin-based combinations. Immune checkpoint inhibitors are becoming an increasingly widely used therapeutic option in many solid tumors. In bladder cancer, a high level of programmed death-ligand is determined by rapidly progressive and aggressive tumors and unsatisfactory survival rates. Although checkpoint inhibitors are effective in metastatic urothelial bladder cancer, only a small proportion of treated patients receive a clear benefit, while a large number of patients experience significant side effects and toxicity without improving quality of life or surviving. None of the available biomarkers at this point was associated with response rates. There is evidence of an correlation between PD-L1 expression, the efficacy of immune checkpoint inhibitors, and treatment outcomes in patients with bladder cancer. A major paradigm shift in bladder cancer medicine has followed the FDA approval of avelumab, pembrolizumab, durvalumab, atezolizumab, and nivolumab for the treatment of patients with metastatic urothelial carcinoma previously treated with chemotherapy. Combining classical clinicopathological parameters with data obtained via information technology, together with genomic profiling, could be the future of personalized therapy for bladder cancer.

This article explores sources of communicative difficulties such as inter-variant polysemy and inter-variant homonymy, focusing on lexemes from the Spanish thesaurus FOOD that denote liquid food products. The relevance of this study is grounded in the necessity for a comprehensive analysis of alimentary semantics within the national variants of the Spanish language in the context of cultural dialogue. The novelty of the research lies in identifying challenges in intercultural communication through semantic, etymological, and linguocultural analyses of the meanings of the examined lexemes and their stable combinations across different Spanish-speaking countries. Particular attention is given to the influence of extralinguistic factors on communicative difficulties within a multi-national language. The findings suggest that the development of semantics for inter-variant homonyms primarily depends on historical factors, and understanding the differences in meanings of core components within semantic fields related to food in various national variants of Spanish can help alleviate communicative barriers and prevent misunderstandings. Future research perspectives include pragmasemantic structuring of the inter-variant alimentary thesaurus in the target language and applying the results to language teaching.

Introduction. A promising area of application of 1,3,5-triazines in medical chemistry is the development of highly effective anticancer agents. It is noteworthy that a significant cytotoxic effect may occur with 2,4,6-substituted 1,3,5-triazine derivatives containing aziridine rings as substituents. These compounds interact with DNA molecules of tumor cells and they are alkylating agents.The objective was to synthesize and investigate the cytotoxic activity in vitro of new aziridine–containing 1,3,5-triazine derivatives against tumor cell lines of human lung adenocarcinoma A549 and human hepatocarcinoma Huh7 and to evaluate the effect of the length of the hydrocarbon radical in the dioxane cycle on the cytotoxic effect of the obtained compounds.Methods and materials. The synthesis of the 1,3,5-triazine derivatives was carried out using 2,4,6-trichloro-1,3,5-triazine (cyanuric chloride) as the starting reagent. The composition and structure of the obtained compounds were proven by elemental CHN analysis and 1H, 13C{1H} NMR spectroscopy. The cytotoxicity was studied using the MTT colorimetric assay.Results. Novel 1,3,5-triazine derivatives were synthesized and fully characterized: (5-((4-(aziridin-1-yl)-6-chloro-1,3,5triazin-2-yl)amino)-2-ethyl-2-methyl-1,3-dioxan-5-yl)methanol and (5-((4-(aziridin-1-yl)-6-chloro-1,3,5-triazin-2-yl)amino)2-isobutyl-2-methyl-1,3-dioxan-5-yl)methanol. Also, cytotoxic effect against tumor cell lines of human lung adenocarcinoma (A549) and human hepatocarcinoma (Huh7) was studied using the MTT assay. It has been shown that an increase in the length of hydrocarbon radicals in the dioxane ring at position C2 leads to a decrease in cytotoxic effect.Conclusion. The synthesized (5-((4-(aziridin-1-yl)-6-chloro-1,3,5-triazin-2-yl)amino)-2-ethyl-2-methyl-1,3-dioxane-5 -yl) methanol and (5-((4-(aziridin-1-yl)-6-chloro-1,3,5-triazin-2-yl)amino)-2-isobutyl-2-methyl-1,3-dioxan-5-yl)methanol cause a dose-dependent decrease against the survival of tumor cell lines A549 and Huh7.

Despite advances in minimally invasive surgery, urolithiasis still recurs within the first five years after the first episode in more than 50% of patients. Researchers continue to search for new crystallisation inhibitors, metaphylaxis strategies and laser sources for stone destruction. Therefore, to achieve these goals, it is necessary to study kidney stones not only as the result of an isolated process of pathological biomineralisation in the human body, but also as a biogenic mineral or rock that obeys universal patterns and has certain properties. Consequently, kidney stones need to be studied using methods that are widely used in the geological sciences for the study of minerals, such as computed microtomography and petrological analysis. In this review, the properties of kidney stones studied using various research methods used in geosciences are discussed. These properties are also considered as new biomarkers of urolithiasis. This review discusses how new data from multimodal stone analysis can be used to develop personalised metaphylaxis and treatment strategies for all types of urolithiasis, including the most common idiopathic calcium-oxalate urolithiasis.

Objective: to determine the sensitivity and specificity of simultaneous analysis of the central vein sign (CVS) and the concentration of free kappa chains (FKC) in cerebrospinal fluid (CSF) in the diagnosis of multiple sclerosis (MS).Material and methods. Eighty patients participated in the study. The main group comprised 54 patients who had been diagnosed with MS according to the 2017 McDonald criteria. The comparison group comprised 26 patients with other diseases of the central nervous system. An enzyme-linked immunosorbent assay was used to determine the concentration of FKC in the CSF. MRI of the brain was performed in all patients. The total and relative number of lesions with CVS were calculated.Results. An increased level of FKC in the CSF and a higher frequency of lesions with CVS were found in the group of MS patients compared to the control group (p

The prevalence of multiple sclerosis (MS) is steadily increasing not only due to rising incidence, but also due to improvements in diagnosis and treatment. Accordingly, there is growing interest in improving the quality of life (QL) of chronic patients, for the assessment of which general scales are used, as well as scales developed specifically for MS. In this work, we analyzed publications devoted to assessing the quality of life of MS patients using the nonspecific SF-36 scale for the period from 2018 to 2023. Data were assessed on all eight scales: physical functioning, role functioning, bodily pain, general health, vitality, social functioning, emotional state and mental health. The usefulness of the SF-36 questionnaire has been shown in the management of patients with MS by a general practitioner for a comprehensive assessment of QL dynamics during treatment and in planning of further treatment and rehabilitation measures. However, the ambiguity of numerous QL studies results in MS obtained using the SF-36 questionnaire requires continued research and improvement of the instrument itself.

Scientists’ misconduct in their research activities is an important problem for science in many countries, including Russia. It leads to negative consequences both for the quality of scientific knowledge obtained and for the reputation of researchers and scientific organizations. However, there is still a small number of empirical studies of this problem in Russia. This work is based on a survey method to explore the ideas of young scientists from all federal districts of Russia about research ethics and the situations of ethical dilemmas that they encounter in their work. In accordance with the chosen theoretical framework: ideas about ethics as an action that is situational by nature, determined by sustainable practices and patterns, the survey was conducted in two stages: an open question about situations of ethical choice in research activities, on the basis of which a detailed questionnaire was then created. As a result, it was revealed that the vast majority of young scientists are faced with situations of violation of ethical standards both in scientific publications and communications, and in the processes of organizing research work. Violations of research procedures, data manipulation, falsification of research results – this is a set of violations in the organization of research that almost three-quarters of respondents encountered themselves or heard about such situations from colleagues. However, there are gaps in consensus about the sources of knowledge about ethics and a lack of institutional practices to prevent violations such as the work of ethics committees or ethical standards.

Objective: to determine the sensitivity and specificity of method of determining the concentration of immunoglobulin free light chains (FLCs) in cerebrospinal fluid (CSF) in the diagnosis and differential diagnosis of multiple sclerosis (MS).Material and methods. 80 patients participated in the study. The main group consisted of 54 patients diagnosed with MS according to the 2017 McDonald criteria. The comparison group (n=26) comprised patients with other diseases of the nervous system. An enzyme-linked immunosorbent assay (ELISA) was used to determine the concentration of FLCs (kappa- and lambda-chains) in the CSF.Results. In the group of patients with MS, an increase in the concentration of free kappa-chains (к-FLCs) in the CSF was found compared to the comparison group (p

A new variety population of meadow clover GPF-49-3, promising for use in agricultural production in the northern regions of the European part of the Russian Federation (RF), has been created in the Federal Agricultural Research Center of the North-East named N. V. Rudnitsky. It is characterized by early periods of mowing and harvesting ripeness: the duration of the growing season from spring regrowth to the flowering phase of the first mowing is 56-72 days, from the first to the second mowing is 39-56 days, until the seeds ripen 103-115 days. According to the results of the study and evaluation in several cycles of competitive and environmental tests (2009–2021) in the conditions of the Kirov region, GPF-49-3 has shown advantages over the zoned standard cultivar (st.) ʻDymkovskyʼ in a number of productive features and adaptive qualities: it is characterized by winter hardiness, tolerance to drought, high productivity and its potential – harvesting of green mass up to 88.3 t/ha, dry matter up to 20.5 t/ha, crude protein up to 2.5 t/ha, seed yield up to 5.3 c/ha. The features of the GPF-49-3 cultivar population are significantly high in comparison with the standard forage productivity of the second year of use (y.u.) – 28.7 t/ha of green mass, 7.8 t/ha of dry matter at the level of standard ʻDymkovskyʼ cultivar – 23.4 and 6.2 t/ha, respectively (LSD05 = 4.5 and 0.8 t/ha), and genetically determined resistance to root rot. A correlation (r) of average strength was found between the intensity of root rot development in 1 y.u. and plant productivity indicators in 2 y.u.: green mass (-0.43), dry matter (-0.50), protein collection (-0.58.), indicating that the herbage with a lower degree of root damage before overwintering is more productive for the next year of use. The obtained research results made it possible to make a decision on the transfer of the GPF-49-3 cultivar population to the state cultivar testing in 2021, as a cultivar of meadow clover ʻMalakhitʼ.

Aim of the study was to investigate susceptibility to pulmonary tuberculosis in men and women depending on polymorphism of genes of xenobiotic biotransformation enzymes NAT2 (590G> A (rs1799930)), CYP2E1 (9896C> G (rs2070676)), ABCB1 (3435T> C (rs1045642)), GSTM1 (E/D) and GSTT1 (E/D). Material and methods. The study included 335 patients with pulmonary tuberculosis aged 18 to 65 years (212 patients with newly diagnosed pulmonary tuberculosis and 123 people with chronic pulmonary tuberculosis receiving intensive phase of chemotherapy). Statistical data processing was carried out on a personal computer using IBM SPSS Statistics 26 and MS Excel 2013 software packages. The control group consisted of relatively healthy individuals without chronic diseases. Genotyping of polymorphisms NAT2 (590G>A (rs1799930)), CYP2E1 (9896C>G (rs2070676)), ABCB1 (3435T>C (rs1045642)) and extended deletions GSTM1 (E/D), GSTT1 (E/D) was performed using real time PCR. Results. It has been established that the genotype EЕ of GSTT1 gene identified in 89.1 % men was statistically significantly associated with increased susceptibility to pulmonary tuberculosis, while the genotype DD of the GSTT1 gene (10.9 % cases) was associated with reduced susceptibility. A similar trend is observed in women: the greatest susceptibility to pulmonary tuberculosis is characteristic for the genotype ЕЕ GSTT1 gene (87.2 %), the least (12.8 %) – for the DD genotype. Conclusions. It is advisable to introduce genotyping of genes of xenobiotic biotransformation enzymes into the practice of a phthisiologist in order to develop measures to improve the effectiveness of prevention and treatment of patients with pulmonary tuberculosis.

Aim. To present data from the AURA Registry (real-world data registry on AlbUminuRia detection rate among patients with previously undiAgnosed chronic kidney disease). It is important to perform population studies both to study the occurrence of markers (albuminuria (AU), decreased glomerular filtration rate (GFR)) and the prevalence of chronic kidney disease (CKD), which will provide information on the actual detection rate of CKD and the related markers in territories included in the registry of research centers.Material and methods. The article presents the first data from the AURA registry. Recruitment was carried out from March 6, 2023 to January 23, 2024. Thirty-four research centers in various federal districts of the Russian Federation and 104 doctors took part in the recruitment. We included 4580 subjects over the age of 40 years who had no previously established diagnosis of CKD and did not have type 1 or type 2 diabetes. During recruitment, the researchers were guided by the AURA study protocol (Version 1.7/12-26-2022).Results. AU more than 20 mg/g was detected in 64,9% of cases. At the same time, AU is more common at GFR values that may correspond to stage 3A of CKD. The rarer occurrence of AU in those examined with GFR >60 ml/min/1,73 m2 may be explained by less severe renal damage at this CKD stage. The incidence of AU was significantly higher in men, older people, smokers, people with metabolic syndrome, hypertension (HTN), prediabetes and overweight. The occurrence of AU also increased as HTN grade increased. AU detection rate was associated with hypertriglyceridemia, a high blood level of C-reactive protein, which is an integrative marker of inflammation that negatively affects cardiovascular risk.Conclusion. The presented first data from the AURA registry demonstrated the high AU prevalence in people over 40 years of age. A high incidence of AU was typical for patients with HTN, coronary artery disease, atrial fibrillation, heart failure, and prediabetes. An association has been demonstrated between the high incidence of AU and male sex, age, overweight, hyperuricemia, dyslipidemia, and a number of other cardiovascular risk factors.

Objective: to evaluate the clinical and economic effectiveness of benralizumab in comparison with standard therapy in patients with severe bronchial asthma (SBA) with an eosinophilic phenotype in the Russian Federation.Material and methods. A clinical and economic analysis of using benralizumab in addition to standard therapy was carried out in comparison with standard therapy for SBA with an eosinophilic phenotype by means of a modeling method. Cost calculations were performed in a mathematical model adapted to the Russian healthcare conditions with the help of cost indicators and patient population characteristics.Results. The use of benralizumab as a mandatory component of standard therapy compared with standard therapy alone for SBA with an eosinophilic phenotype will allow for an additional 0.65 life years gained (LYGs) and 1.12 quality-adjusted life years (QALYs) per 1 patient during lifelong therapy. It will provide avoiding 4.95 exacerbations, simultaneously with a reduction in total costs by 584,144 rubles by reducing gross domestic product (GDP) losses due to mortality and temporary disability over an assessment horizon equal to life expectancy. The costs of 1 LYG and 1 QALY in the case of benralizumab were 869,455 and 1,252,056 rubles, in the case of standard therapy they were 911,615 and 1,303,811 rubles, respectively.Conclusion. Intensification of SBA therapy with an eosinophilic phenotype with benralizumab is clinically justified (leads to an increase in life expectancy, a decrease in the rate of exacerbations and an increase in patients’ working life), and is also economically feasible, as it allows to reduce direct costs and GDP losses of the state.

Histologically, chronic demyelinating lesions in multiple sclerosis (MS) have been shown to include inactive lesions that do not change over time and active or “smouldering" lesions that tend to enlarge over time and are surrounded by pro-inflammatory activated microglial cells that are loaded with iron. To identify “smouldering" foci of demyelination and assess the “latent” inflammatory process in the brain, MRI sequences sensitive to the detection of substances with paramagnetic properties, including iron, must be used. They include an innovative technique such as quantitative susceptibility mapping (QSM).Objective: to identify, using MRI different types of chronic demyelination foci in MS, based on iron distribution and the degree of damage (myelination) in their structure.Material and methods. The patterns of iron distribution in demyelinating lesions in 90 MS patients were investigated using QSM. In addition, two lesions with different iron distribution patterns were randomly selected on the QSM map for each patient, in which the magnetic transfer ratio (MTR), indirectly reflecting the degree of myelination, was calculated. The identified changes were also compared with visualization of lesions in standard MRI modes (T1 MPRAGE, T2 FLAIR).Results. Despite the predominantly identical visualization in T2 FLAIR mode, chronic foci of demyelination show different patterns on the QSM maps, which is due to the peculiarities of iron distribution: some foci are not detected on QSM, while others are visualized either in the form of a homogeneous or a ring-shaped pattern. When comparing QSM data with MTR, it was found that MTR indicators were highest in non-visualized lesions (demyelination is minimal), while damage was most pronounced in lesions with ring-shaped iron distribution.Conclusion. Different patterns of iron distribution in demyelination foci compared to the degree of myelination in these foci according to MTR were identified using QSM, which is of great importance for the evaluation of latent inflammation and the development of the neurodegenerative process in MS.

Currently, more than 15 molecules are already approved for the treatment of multiple sclerosis, and sometimes physicians encounter problems selecting a drug for therapy when considering patients with the initial equivalent characteristics. When selecting a drug, it is important to consider not only the efficacy and safety of the drug, but also the possibility of further therapy after discontinuation of the initially selected drug. This paper discusses the results of clinical trials on the efficacy and safety of ofatumumab and its potential advantages over other anti-CD20 agents.

Currently, a decrease is seen in the effectiveness of treatment in patients with tuberculosis due to the appearance of adverse reactions to anti-tuberculosis drugs. Hepatotoxic reactions play an especially important role in anti-tuberculosis therapy, and phthisiologists often have to deal with the cancellation of a number of anti-tuberculosis drugs. The aim of the study was to investigate the relationship of polymorphic gene variants of xenobiotic biotransformation metabolizing enzymes (NAT2 (590G>A (rs1799930), CYP2E1 (9896C>G (rs2070676), ABCB1 (3435T>C (rs1045642), GSTM1 (E/D), GSTT1 (E/D) with the risk of hepatotoxic reactions in patients with pulmonary tuberculosis. Material and methods. The logistic regression analysis method was used to predict the probability of hepatoxic reactions during specific anti-tuberculosis therapy. Results: 1 statistically significant model was obtained, which reflects the association with hepatotoxic reactions to anti-tuberculosis drugs of the TS genotypes or the TS gene (T allele) ABSV1 (rs1045642). Conclusion. Pharmacogenetic testing used in the study allows us to identify risk groups of patients with pulmonary tuberculosis according to the likelihood of hepatotoxic reactions, which may provide an individualized approach to the treatment of these patients in the future.

Aim. To identify predictors of cardiovascular events (CVEs) in patients with heart failure (HF) and P. aeruginosa pneumonia.Material and methods. The study included 92 patients with HF with mildly reduced or reduced ejection fraction and nosocomial pneumonia. Based on sputum or bronchoalveolar lavage microbiological examination, patients were divided into 2 following groups: group I — 51 patients with HF and P. aeruginosa pneumonia, group II — 41 patients with HF and pneumonia caused by other pathogens (Staphylococcus aureus, Streptococcus pneumoniae). During the hospital stay, the following morbidities were assessed: cardiovascular death, acute coronary syndrome, non-fatal cerebrovascular accident, pulmonary embolism, lower extremity venous thrombosis.Results. CVEs were significantly more often observed in patients with HF and P. aeruginosa pneumonia — 30 (58,8%) than in patients with HF and pneumonia caused by S. aureus or S. pneumoniae — 5 (12,1%). Complete blood count in group I patients revealed a decrease in hemoglobin level to 114 [95; 133] g/l, when compared with patients in group II — 139 [118; 150] g/l (p11×109/l (RR 2,412; 95% CI 1,399-4,158; p=0,048), CRP >133 mg/l (RR 3,115; 95% CI 1,611-6,025; p

Aim. To assess the contribution of Pseudomonas aeruginosa pneumonia to the development of cardiovascular events in patients with heart failure (HF).Material and methods. The study included 219 patients who were divided into a group of patients with pneumonia caused by P. aeruginosa (Group I) and a group of patients with pneumonia caused by S. aureus, S. pneumoniae (Group II). All patients underwent chest computed tomography (CT), blood tests, echocardiography, electrocardiography (ECG), 24-hour Holter ECG monitoring, pulse oximetry (SpO2), and Doppler ultrasound of the lower limb veins.Results. According to the study, cardiovascular events were more often observed in the group of patients with P. aeruginosa pneumonia as follows: death from cardiovascular events was registered in 11,4% of patients in group I and 0% of patients in group II (p=0,001); acute coronary syndrome — in 8,7 vs 0% (p=0,002), lower limb thrombosis — in 14 vs 1,9% (p=0,001). The occurrence of P. aeruginosa pneumonia in patients with HF increased the cardiovascular death risk by 8,8 times (95% confidence interval (CI): 1,2-65,7; p=0,005), acute coronary syndrome — in 8,0 times (95% CI: 1,1-60,2; p=0,014), lower limb thrombosis — in 9,6 times (95% CI: 1,3-71,2; p=0,004).Conclusion. Patients with HF and P. aeruginosa pneumonia are at greater risk of cardiovascular events than patients with pneumonia caused by S. pneumonia and S. aureus.

The purpose of the research is to assess the condition of the black-backed sea shad (Alosa kessleri, Grimm, 1887) in the Lower Volga according to parasitological, microbiological, toxicological, and biochemical parameters, and to determine the correlation between the above during the spawning. Materials and methods. The research object was the black-backed sea shad caught with a river shore seine. Sampling for comprehensive studies was performed from 15 black-backed sea shads during the spawning migration in 2017. The fish were studied by the method of partial parasitological dissection (the protozoa class was not studied). The fish were collected and dissected, and cameral treatment was performed per Bykhovskaya-Pavlovskaya method. Microbiological studies were conducted by common methods. Species identification of identified helminths and microorganisms was performed according to standard identification guides. Toxicological studies included the determination of lead, cadmium, mercury, and petroleum hydrocarbons in the muscle tissue of the studied shad specimens by atomic absorption. In fish muscles, we studied the number of total lipids by the Zollner method, and water-soluble protein by the spectrometric Warburg-Christian method. The Fulton's condition factor was used for fatness determination. The obtained results were processed statistically. Results and discussion. The results of the comprehensive studies of commercial species of the black-backed sea shad (Alosa kessleri, Grimm, 1887) showed that the parasite fauna of fish was distinguished by a poor species composition as contracted with a qualitative microbiota biodiversity. Infection of the black-backed sea shad proceeded at the asymptomatic carrier level, which indicated a balanced relationship between parasites and the host. The levels of accumulated toxicants in shads were close to the characteristic values for fish in the Volga-Caspian basin. On average, the stock of energy resources in the studied fish had a positive trend in relation to the previous research period. The study results of the black-backed sea shad during the spawning showed the correlation of parasitological, microbiological, toxicological, and biochemical parameters that comprehensively affect the general physiological state of the studied fish.

Multiple sclerosis (MS) is an autoimmune inflammatory neurodegenerative disease of the central nervous system. The disease is characterized by a heterogeneous clinical course, which is reflected in the fact that there are various types, such as relapsing-remitting MS (RRMS), primary and secondary progressive MS (PPMS and SPMS, respectively). Currently, there is an active search for MS biomarkers capable of predicting and assessing disease progression with high sensitivity and specificity, which would be of great benefit in determining treatment tactics and evaluating their efficacy. MicroRNAs (miRNAs) are short (21–25 nucleotides) non-coding RNA molecules that are primarily involved in post-transcriptional regulation of gene expression. miRNAs play an essential role in tissue development, homeostasis, immune system regulation, and immune cell maturation; they are also involved in the pathophysiology of MS. In addition, high hopes are pinned on miRNAs as disease biomarkers, mainly due to their stability and ability to be released from cells into the extracellular space and circulate there for a long time. The review considers published data on miRNAs in different types of MS. In the future, changes in their levels may be used to create a panel of prognostic markers for disease progression. Studies of miRNAs levels in both circulating fluids (plasma, serum, cerebrospinal fluid) and brain tissue of MS patients were reviewed. Based on the aggregated data from the studies reviewed, it can be confirmed that the accumulated data are quite sufficient to recognize that regulatory miRNAs molecules are involved in the pathophysiological mechanisms of MS progression. However, there is still a long way to go to establish a panel of circulating miRNAs that predict the rate of progression of MS.

Cataract in patients of older age groups is one of the reasons for the deterioration of geriatric status, the manifestations of which are geriatric syndromes, but insufficient attention paid to the study of the latter.Purpose. To study the prevalence of geriatric syndromes among patients with UC, depending on visual acuity without correction.Patients and methods. Geriatric syndromes were studied in 220 elderly patients with UC, in 240 elderly patients with FC and 200 elderly patients without UC based on methods of complex geriatric assessment. The following geriatric syndromes were analyzed: sarcopenia, hypomobility, malnourishment, pain syndrome, and disorders of general motor activity, psychological problems, cognitive disorders, anxiety-depressive status, sleep disorders and urination.Results. It was found that the deterioration of visual acuity without correction of less than 0.3 is accompanied by an increase in the majority of geriatric syndromes in elderly and senile patients with UC and especially in 75–89 years of hypomobility syndrome to 93.2 ± 2.5 cases of cognitive impairment to 89.3 ± 3.0 cases, malnutrition to 88.3 ± 3.2 cases and psychological problems to 79.6 ± 4.0 cases per 100 examined, which is significantly higher by 2.0–2.4 times compared to patients of the same age with UC with visual acuity without correction more than 0.3. A decrease in visual acuity of less than 0.3 in patients with UC contributes to an increase in the prevalence and average number of geriatric syndromes in old age to 8.2 ± 1.0 cases versus 3.9 ± 0.8 cases in old age with UC with visual acuity of more than 0.3 (P < 0.001).Conclusion. The revealed dependence of the prevalence of geriatric syndromes, taking into account visual acuity, indicates the relevance of timely correction.

Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease of unknown etiology, characterized not only by joint destruction, but also by visceral organ involvement. Interstitial lung disease is considered the most common and serious pulmonary complication of RA, with a prevalence of about 50% according to most studies. As a rule, involvement of the lungs occurs several years after the onset of RA. The article presents a description of a clinical case of the development of respiratory disorders (severe dyspnea) as early as a month after RA onset.

The paper describes the problem of standardization of the formation of non-financial reporting of Russian commercial organizations, since the information requests of stakeholders are growing, in connection with this, commercial organizations are facing the problem of optimal disclosure of information about all aspects of their activities. The aim of the study is to analyze international standards and modern trends for the disclosure of non-financial in the standardization of information disclosure in reporting of Russian domestic companies and the possibility of their application for its formation. The methodological base of the study includes fundamental concepts and approaches, fundamental provisions of economic science and applied developments, substantiated by the works of foreign and domestic scientists in the field of non-financial reporting. The authors reviewed various approaches to understanding the materiality of reporting in terms of the amount of information covered by its various types. In the work’s course, the authors studied the existing international standards used by all commercial organizations in the preparation of their reports on sustainable development (using the GRI standards), as well as they proposed a critical analysis of the GRI and SASB standards and the content of the integrated report. Also, the reaserch highlited the features of GRI, SASB and IIRC. The theoretical and practical significance of the study lies in the generated recommendations for the standardization of non-financial reporting for Russian commercial organizations.

The article presents the results of many years of research (2011-2021) on determining the quality of Hungarian clover (Trifolium pannonicum Jacq.) seeds of Snezhok variety obtained in the conditions of Kirov region (North-East of the European part of Russia). The weight of 1000 seeds averaged 4.16 g with changes over the years from 3.83 to 4.60 g and depended on the amount of precipitation (r = 0.71), the hydrothermal coefficient during the flowering period of grass stands (r = 0.69), average daily and daytime air temperatures during the "flowering-the beginning of maturation" period (r = -0.70). On average, the length of the seeds was 2.45 mm, width – 1.93 mm; thickness – 1.40 mm. According to the ratio of these parameters, the seeds had an ovoid and ellipsoid (elongated) shape. The size of the seed material (integral indicator) did not exceed 2.0 mm. In years with greater moisture availability (98-189 % to the norm) large seeds were formed (from 1.92 to 2.00 mm), with insufficient moisture (64-81 %) ‒ small seeds (1.78 mm). According to the initial germination indicators, all seed material met the requirements of GOST R 52325-2005 and was classified as "original seeds". Germination and germinating energy were 86.7-99.5 and 80.0-97.0 %, respectively, they depended on the average daily air temperature during the "budding-seed ripening" period (r = 0.66 and 0.68) and remained at a high level for the first three to four years of storage. The seed material had mainly a low content of hard seeds (1.5-7.0 %). In some years, the "hard-seeding" of freshly harvested seeds reached 20.0-36.0%, however, after the post-harvest ripening period, it significantly decreased. The freshly harvested seeds had a yellow color, which gradually changed to beige-brown or brown-beige during storage. Regression analysis showed a strong relationship between the color of seeds of different storage periods and germination rates. The presence of a large number of yellow seeds in the batch indicated to their high germinating energy (r = 0.98) and germination (r = 0.95). the predominant content of brown seeds indicated to the loss of seed sowing qualities (r = -0.94 and r = -0.91, respectively).

The article deals with the issue of semantic discrepancies between the lexical units of the Spanish language national variants on the example of the semantic field “Bread and baking” lexemes. The relevance of the study is due to its focus on the needs of the current stage of development of comparative semantics, variantology and intervariant dialectology, which provide for the gradual coverage of all the supporting semantic fields of the language in the communicative-pragmatic aspect. The novelty of the study is seen in the fact that through a comparative intervariant analysis of language units with the primary meaning of baking, the cultural specificity of the corresponding concepts in different Spanish-speaking countries and regions within the framework of a multinational language is revealed. Particular attention is paid to the semantic processes and linguistic phenomena underlying the intervariant discrepancies, their classification is proposed in relation to this area. The question is raised about the importance of extralinguistic factors in the formation of the alimentary thesaurus of a particular country and culture or sets of cultures in a certain territory. As a result of the study, it was proved that the vocabulary of the field “Baking” is a source of difficulties in intercultural communication, directly related to linguistic phenomena in the field of variantology and intervariant dialectology of the Spanish language.

Aim. To evaluate the cost-effectiveness of empagliflozin therapy in patients with heart failure (HF) across the ejection fraction (EF) range in the Russian Fe­­deration.Material and methods. An analysis of the cost of HF management was carried out and an analytical decision-making model was built in MS Excel, which makes it possible estimating the costs of HF management with empagliflozin from the state position.Results. Taking into account the direct costs of adverse events, as well as indirect costs, the potential economic benefit of empagliflozin use for 766028 HF patients with low EF could be RUB 7,6-7,8 billion per year of therapy, while for 5790280 patients with HF with moderately reduced and preserved EF — RUB 27,6-29,6 billion per year of therapy. The potential economic benefit of empagliflozin for 664960 patients with HF immediately after hospitalization for an HF exacerbation could be RUB 1,4-1,6 billion per year of therapy, allowing to prevent 69438 deaths and 60822 repeated exacerbations of HF.Conclusion. Empagliflozin is the optimal regimen for the treatment of patients with HF across the entire EF range, both with and without type 2 diabetes, both in terms of clinical efficacy of treatment and economic feasibility.

Systemic sclerosis (SSc) is a disease characterized by vasculopathy, fibrosis of the skin and internal organs, most often complicated by interstitial lung disease (ILD). The incidence of SSc reaches 20 cases per 1 million population per year, while changes in the lungs are found in more than half of patients and are characterized by a rapid increase in fibrosis, poorly controlled respiratory failure, and an unfavorable prognosis. It is important to trace the features of the formation and course of ILD and its relationship with occupational hazards in patients diagnosed with SSc. Dust pathology of the respiratory organs (chronic dust bronchitis and silicosis) is most typical for people with long work experience in mining. Silicosis in these patients may be accompanied by SSc with rapid progression of bronchial obstruction, restrictive disorders, as well as myocardial involvement and the development of pulmonary hypertension.

Liver cancer remains a global challenge of healthcare, with the incidence growing worldwide. According to various authors, over 1 million patients will be diagnosed with liver cancer each year by 2025. The molecular pathogenesis of HCC varies with respect to genotoxic lesions and aetiologies. Although our understanding of the HCC pathophysiology and drivers tends to improve, it is still distant from translation into clinical practice. About 25 % of HCC cases are associated with variant mutations. HCC pathophysiology is a complex multi-step process. The interaction of various factors underlies the early stages of malignant hepatocyte transformation towards the development of HCC. Overall, about 20–25 % of HCC patients have at least one potential driver mutation. Obesity should also be noted as being associated with a higher risk of HCC and various other cancers. Despite many issues in the HCC pathogenesis being already known, the unresolved questions remain. Modern molecular genetic diagnostics and animal modelling of malignant tumours are expanding our horizons of knowledge in this field.

Metastatic renal cell carcinoma accounts for almost 85% of all cases of malignant neoplasms of the kidney. Sunitinib is an anti-angiogenic tyrosine kinase inhibitor, one of the indications is the treatment of mRCC in adults. Sunitinib is an oral tyrosine kinase inhibitor that includes the vascular endothelial growth factor receptor (VEGFR) and the platelet-derived growth factor receptor (PDGFR). Sunitinib is primarily used as a first-line drug at an initial dose of 50 mg. 1 time per day for 4 weeks followed by a 2-week break. Recommendations, if dose modification is necessary, indicate a dose reduction to 37.5 mg per day and, if necessary, a further dose reduction to 25 mg per day. Another promising regimen is to continue the daily dose of 50 mg with more frequent breaks: 2 weeks of treatment followed by a pause of 1 week. The analysis presented in the article shows that patients with mRCC who switched to sunitinib 2/1 regimen due to adverse events from the standard 4/2 regimen do show an improved safety profile. There is evidence of a significant reduction in overall grade 3-4 toxicity, as well as a reduction in the incidence of specific drug toxicity such as fatigue, hypertension, hand and foot syndrome, and thrombocytopenia. The article presents a clinical observation of a patient with advanced renal cell carcinoma who has a contraindication for immunotherapy. The patient underwent cytoreductive laparoscopic resection of the left kidney. Taking into account the existing contraindications to immunotherapy, the patient was prescribed sunitinib monotherapy at the standard dosage in the first line. After two courses of therapy, due to adverse events, the therapy regimen was changed from 4/2 to 2/1. The ongoing therapy in the 2/1 regimen demonstrated a satisfactory safety profile with adequate clinical efficacy.

Hepatocellular carcinoma is a common type of liver malignancy and one of the leading causes of cancer death worldwide. In the Russian Federation, according to statistical reports, there is also an increase in the incidence. For over 10 years, the tyrosine kinase inhibitor sorafenib has been the only approved treatment for advanced hepatocellular carcinoma. Lenvatinib was registered as the second drug for the treatment of advanced hepatocellular carcinoma in the first line. In the era of checkpoint inhibitors, the possibility of such therapy in the first and subsequent lines of advanced hepatocellular carcinoma remains relevant. The combination of atezolizumab with bevacizumab in a phase III study (IMbrave150) improved treatment outcomes such as overall survival and progression-free survival. The results of the phase III randomized trial IMbrave 150 showed undoubtedly better efficacy of the atezolizumab + bevacizumab combination compared to sorafenib in terms of a median progression-free survival of 6.8 vs 4.3 months. The above clinical observation demonstrates the result of treatment of a patient with advanced hepatocellular carcinoma with a combination of atezolizumab and bevacizumab. After verification of the diagnosis, since January 2021, therapy with a combination of atezolizumab 1200 mg, bevacizumab 15 mg/kg was started with an interval of 21 days.At present, 20 courses of therapy have been carried out in this regimen, and the stabilization of the disease is maintained. Against the background of the ongoing therapy, no adverse events were noted, including immune-mediated ones that required the abolition or reduction of doses of drugs. In the above clinical observation, a patient with severe comorbidity achieved stabilization of the disease in the first three months of therapy. Combination therapy showed a favorable tolerability profile.

Pancreatic adenocarcinoma has a 5-year overall survival rate of 9 %, with an outlook of becoming the second leading cause of cancer mortality in the USA by 2030. Familial pancreatic cancer and genetic predisposition syndromes have attracted more interest in the perspective of targeted therapy. Various authors estimate genetic causes to account for 10–15 % of pancreatic cancers. The BRCA gene mutations comprise the today’s most relevant genetic predisposition syndrome. The frequency of BRCA1/2 and PALB2 germinal mutations in patients with pancreatic adenocarcinoma constitutes about 5–9 %. Over recent years, PARP inhibitors (PARPi) have composed a new targeted therapy class with a significant effect in breast and ovarian cancers. With the mechanism of action of the PARP inhibitor and platinum drugs targeting different DNA repair pathways, their combination therapy has been suggested as promising. We report studies of a combination treatment with veliparib, gemcitabine and cisplatin in germinal BRCA1/2-mutation patients with advanced wild-type pancreatic adenocarcinoma (WT). Recent advances have identified patients with germinal and somatic mutations in the BRCA1/2 and other genes. HRD-targeted therapy, including platinum and PARP inhibitor drugs, can significantly improve survival.

The need to review the guidelines for the management of patients with multiple sclerosis using multiple sclerosis disease modifying drugs has become acute enough since the beginning of 2020 following the outbreak of the COVID-19 pandemic caused by a novel coronavirus SARS-CoV-2. Immunosuppressive drugs were also specifically addressed, as it is during administration of these drugs that the more severe course of COVID-19 disease was expected. Both the Russian and foreign teams published results of their research works. This article presents a retrospective analysis of the incidence rates of COVID-19 in patients with multiple sclerosis after selective immunosuppressive therapy with alemtuzumab and a clinical case when a patient was infected with coronavirus in the first days following the last infusion of the therapy course without clinical manifestations of the infectious disease. The author discusses the mechanisms underlying such a favourable outcome due to the CD52 lymphocyte depletion leading to the reduction of risks of developing hyperimmune reactions that underlie severe complications of COVID-19, and analyses previously published works of our foreign colleagues on the same theme. The review of the accumulated works and personal experience suggest that it is the CD52 lymphocyte depletion that makes it possible to avoid the cytokine storm and, as a result, the more severe course of COVID-19. Amidst the COVID-19 pandemic, during the prescription of multiple sclerosis disease modifying drugs, it should be borne in mind that patients should have access to all types of modern therapy and that the benefits should outweigh the sum of possible risks.

Aim. To evaluate the potential of a fixed-dose combination of lisinopril+amlodipine+rosuvastatin (Equamer®) in achieving additional vascular protection in patients with hypertension and high pulse wave velocity (PWV) after severe and very severe coronavirus disease 2019 (COVID-19), complicated by bilateral multisegmental viral pneumonia, with the use of biological therapy, who had not previously received combination antihypertensive therapy.Material and methods. This 12-week open-label observational study included 30 patients with or without antihypertensive therapy. The patients underwent 24-hour blood pressure monitoring, applanation tonometry (determination of the augmentation index (AI) and central blood pressure (CBP)), PWV measurement, blood laboratory tests (lipid profile, fasting glucose, C-reactive protein, complete blood count, ferritin, fibrinogen, D-dimer, alanine aminotransferase, aspartate aminotransferase, creatinine, uric acid) before and after switch to a fixed-dose combination of lisinopril+amlodipine+rosuvastatin.Results. At baseline, the patients had an increase in office blood pressure (BP) up to 152,6/89,1 mm Hg. After prescribing a fixed-dose combination of lisinopril+amlodipine+rosuvastatin, there was a decrease in systolic blood pressure (SBP) by 15,8% and diastolic blood pressure (DBP) by 12,2%. According to 24-hour blood pressure monitoring, the decrease in SBP was 15%, DBP — by 9%, PWV — by 23,8%, AI — by 9%, CBP — by 12,4% (p