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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.

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.

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.

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.

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.

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).

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.

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.

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.

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.

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.

Neuromyelitis optica spectrum disorders (NMOSDs) are autoimmune inflammatory disorders accompanied by central nervous system damage, widespread immunemediated demyelination, and axonal damage, involving mainly the optic nerves, spinal cord, and area postrema. The diagnostic capabilities, administration and routing of patients, and therapeutic approaches to this disease need to be improved. During several expert councils held in 2019–2021 in different regions of the Russian Federation, we discussed multiple issues related to various aspects of medical care for patients with NMOSDs. As a result, the experts developed further steps necessary to improve the medical care to these patients: to write and publish clinical guidelines for the diagnosis and treatment of NMOSDs; to consider the possibility of optimizing the NMOSDs diagnostic program including the aquaporin-4 antibodies (AQP4-IgG) testing; to evaluate the implementation of a set of measures aimed at including the corresponding laboratory investigations into the system of state guarantees (together with the institutions of the Ministry of Health of Russia), if there is clinical and economic feasibility; to include the issues of timely NMOSDs evaluation in educational programs initiated by the scientific medical community, in order to raise awareness of primary care neurologists in relation to the clinical and neuroimaging signs of probable NMOSDs; to assess the possibility of introducing routing schemes for patients with NMOSDs at the regional level; to work out a decision on the collection of NMOSDs epidemiological and clinical data in the Russian Federation.

The COVID-19 pandemic was announced in 2020, and many professional medical societies had to review their algorithms for the management of high-risk patients. In addition to risk factors such as overweight, age over 65 years, cardiovascular disease, diabetes mellitus, and bronchial asthma, other chronic diseases should also be emphasized, taking into account possible immunosuppressive therapy. This publication presents two clinical cases of COVID-19 infection in patients with multiple sclerosis treated with ocrelizumab. During the course of the disease, both patients developed a cytokine storm and were treated with IL-6 blockers. Both cases ended with recovery and a subsequent return to anti-B-cell therapy. Given the mechanism of action of ocrelizumab, there are higher risks of infectious complications, including with COVID-19, but mortality is not higher than the population average. The information published to date may serve as a reason to consider the use of extended dosing intervals to minimize the possible risks of COVID-19 infection, which are probably highest in the first months after infusion.

Purpose: to prepare and characterize calcium-phosphate nanoparticles loaded with compounds of different nature: low-molecular inhibitor of angiotensin-converting enzyme lisinopril, and high-molecular enzyme superoxide dismutase 1. To estimate the possibility of enhancing the biological efficacy of these compounds via incorporation to the nanoparticles.Material and methods. To increase the stability of calcium-phosphate nanoparticles coating with β-D-cellobiose was used. The size, surface charge (ζ-potential) of the particles and efficacy of including of the selected compounds to the particles were measured. Comparative assessment of the efficacy of lisinopril solution and lisinopril in nanoparticles was made via the estimation of their ocular hypotensive effect in normotensive rabbits. To compare the efficacy of the superoxide dismutase 1 solution and superoxide dismutase 1 in nanoparticles the rabbit model of immunogenic uveitis was used. We estimated the clinical score for several signs of uveitis, protein level, and antioxidant activity in aqueous humor.Results. Calcium-phosphate nanoparticles containing lisinopril had average hydrodynamic radius of 170–300 nm and negative ζ-potential of –17 mV. Particles containing superoxide dismutase 1 had average hydrodynamic radius of 220–450 nm and negative ζ-potential of –4 mV. Lisinopril in nanoparticles caused a significantly greater decrease of intraocular pressure than lisinopril solution. Superoxide dismutase 1 in calcium-phosphate nanoparticles more efficiently decreased the clinical manifestations of uveitis and normalized the biochemical processes in aqueous humor than the enzyme in buffer solution.Conclusion. Incorporation of both low-molecular and high-molecular drugs to the calcium-phosphate nanoparticles enhance their bioavailability and therapeutic efficiency. The data obtained give evidence of the prospectively of the using of these nanoparticles as vehicles for the ophthalmic drugs used in eyedrops.

Currently, there are negative trends in the incidence of cataract, which, along with glaucoma, is the most common cause of visual impairment in various countries. Cataract prevalence continues to be high, necessitating the search for new treatment technologies and criteria for assessing the health and quality of life of this population. The purpose: to study the quality of life of patients with cataract against the background of ultrasonic phacoemulsification with implantation of soft intraocular lenses. Nei-VFQ-25 quality of life was studied in 182 patients with nuclear–cortical form of cataract before and after ultrasonic phacoemulsification. The integral index and components of the quality of life of patients with cataract before treatment are significantly reduced. The quality of life of patients with cataracts significantly increases in 3 months after surgical treatment in all indicators. Especially vision significantly improved in the distance, near vision, General health. Improving the quality of life of patients with cataracts after treatment indicates the effectiveness of the used ultrasonic phacoemulsification. In this case, the cause is a violation in the field of role-playing physical and emotional functioning. In the long-term period (6 months after treatment) there is an improvement in the quality of life of patients with mechanical trauma in many respects, except for the role of physical functioning. This study for the first time revealed the effect of ultrasonic phacoemulsification with implantation of soft intraocular lenses on the quality of life of patients with cataract. For the first time using a specific questionnaire NEI-VFQ-25 revealed the scale on which there is an improvement in the quality of life after surgery. The leading indicators of quality of life of patients with cataracts, characterizing the effectiveness of treatment with high-tech method of ultrasonic phacoemulsification, were established for the first time.

The article presents the results of the discussion of the use of anti-B-cell therapy in multiple sclerosis (MS). These cells play a significant role in immunoregulation in MS, not only by producing antibodies to myelin antigens after transformation into plasma cells, but also by presenting the antigen to T cells, producing activation cytokines, and forming laminar follicles. The article provides an expert consensus statement on different drugs of this class in the MS treatment. In addition, the possibilities of determining the disease prognosis for the initially correct treatment choice are highlighted. Undoubtedly, there is a need for confirmation of the MS diagnosis, possible stratification of patients into different risk groups, and evaluation of the response to therapy. Potential additional research methods included evoked potentials and optical coherence tomography, baseline vitamin D3 level as a prognostic marker of the disease course, neurofilament levels in serum and cerebrospinal fluid to confirm neuron damage. However, it takes much time to study, determine the methodology, reference values, and develop a single standard approach to identify and implement a biomarker, which should then be implemented in routine clinical practice.

The article presents the results of 2016-2020 study of the characteristics of growth and development of the pannonian clover variety Snezhok, bred at the Federal Agricultural Research Center of the North-East named N.V. Rudnitsky, while using the herbage for seeds. Uneven-aged herbage was assessed in the breeding nursery of 2016 sowing according to the characteristics of winter hardiness, the duration of individual interphase periods of development, plant height, structure of seed herbage, fruiting and seed yield. The overwintering of plants in all the years of research was high ‒ 100%. With an increase in the age of the stand, the prefloral (from growing to the beginning of flowering) and growing seasons from 47 to 72 and from 92 to 125-130 days (days) were lengthened. The height of plants in the phase of maturation of heads and seeds with the age of the stand also increased from 66.6 (1 year of use (y.u.)) to 97.1 cm (4 y.u.), the tendency of herbage to lodging increased from 0 (1 y.u.) to 30.9% (4 y.u.). In the first year of seed use (the 2 nd year of life (y.l.)), the minimum values of such structural indicators as the number of stems and heads per 1 m2 (245 and 151 pcs.), The content of generative stems in the total amount (42.8%), weight of seeds per 1 m2 (15.3 g). Starting from the 2 nd y.u. the listed structure indicators significantly increased and herbage stands were formed annually for three years, allowing them to be classified as highly productive: with the stem density of 366-405 pcs / m2 and a share of generative ones in them - 59.0-84.2 %, the number of heads - 350 -500 pcs / m2 , seed weight - 31.5-46.1 g / m2 . The level of seed productivity of pannonian clover depended to a greater extent on the age of the stand than on weather conditions during the period from regrowth to seed ripening. It was revealed that the biological (potential) seed yield in favorable years with sufficient technical support can reach 4.33 c/ha, while the actual (economic) average over the years of research was 0.54 c/ha, with changes from 0.20 (2017) up to 0.74 c/ha (2020).

The article presents the results of a long-term study (2014-2018) of the biological characteristics of growth and development of plants of the introduced species – red feather clover (Trifolium rubens L.) when growing grass stands for seeds in the soil-and-climatic conditions of the Volga-Vyatka region. The species was assessed for winter hardiness, the duration of the growing season, plant height, structure of seed grass stand, seed productivity and seed quality. Winter hardiness of red feather clover in all years of cultivation was high (more than 80 %). The development of plants took place according to the mid-season type: depending on the conditions of the year of growth, they reached the flowering phase for 61-75 days; ripening phase – for 82-105 days from the beginning of regrowth. The duration of grass stand flowering was 14-40 days, ripening – 15-39 days. During the phases of development, the species is responsive to changes in the meteorological conditions of the year of study. In the first and second years of life, the active formation of the root system of plants took place, therefore, taking into account the structure of the seed grass, the height of the plants, the density of the stalk and the proportion of generative stems in the grass, the number of heads and the weight of seeds per 1 m2 was lower than in subsequent years. Productive in seeds grass stand was formed since the third year of life and reached a plant height in the flowering phase of 49.2-56.2 cm, in the ripening phase – 50.4-63.4 cm. It was characterized by the density of the stems standing of 1019.7-1151.6 pcs/m2 with the proportion of generative stems – 96.0-99.6 %, the number of mature heads – 978.9-1147.0 pcs/m2 and seed productivity – 18.8-55.0 g/m2. Seed production was regular, despite strong fluctuations in yield. The seed material was of high quality: seed germination – 94-100 %, germination energy – 58.3-81.3 %, and was characterized by 1000-seed mass of 2.25-2.38 g, hard seed content – 9.1-20.0 %.

An increased percentage of the elderly subjects in pattern of contemporary society, along with other causes and risk factors, is accompanied by rise in the incidence of glaucoma. By 2020, according to international studies it is expected that prevalence of glaucoma patients in the world would increase up to 80 million subjects. Among the elderly, glaucoma is a common pathology, which development is associated with local disturbances in interleukin profile. However, the features of the latter in patients with primary closed-angle glaucoma in the elderly were poorly examined. Studies of local interleukin status were conducted mainly in patients with suspected or initial manifestations of primary open-angle glaucoma. The features of lacrimal fluid interleukin shift in a target group of elderly patients suffering from stage II primary closed-angle glaucoma virtually gained no attention. In addition, a limited range of local interleukins in patients with such pathology in previous studies was examined. In addition, informativity of lacrimal fluid interleukins in elderly glaucoma patients was not assessed too based on objective methods. The aim of the current study was to outline features and informativity of local interleukin profile indicators in 58 elderly patients with primary closed-angle glaucoma stage II, aged 60—74 years (main group) and 27 age-matched elderly subjects lacking such pathology. The level of interleukins in the lacrimal fluid was determined with the enzyme immunoassay “Multiscan” analyzer (Finland) by using sandwich ELISA (R&D Diagnostic Inc., USA). Informativity of measuring various interleukins was calculated according to the generally accepted formula. It was found that local interleukin profile in elderly patients with primary closed-angle glaucoma was mainly featured with increased amount of IL-2, IL-17, IL-8, but decreased IL-10. Hence, such local interleukins displayed peak informativity. The data obtained should be used in the diagnostics and treatment of such pathology, as well as of applied importance to unveil novel mechanisms behind development, diagnostics and corroboration for selective immuno-tropic therapy of primary closed-angle glaucoma.

The article presents the results of research work on the assessment of general combining ability (GCA) and specific combining ability (SCA) in 14 varieties of meadow clover (Trifolium pratense L.) of various ecological and geographical origin (Russia, Belarus). The study was aimed at identifying the best varieties according to productivity indicators for inclusion into the breeding process in the conditions of the Volga-Vyatka region. The study of initial cultivars and their hybrid forms F1 was carried out in the field experiment of 2009 with two-year use of grass stand (2010, 2011). The characteristics of cultivars according to the main morphological and biological characteristics (winter hardiness, length of the vegetative period, plant height, grass stand vigour) and economically significant indicators (collection of raw and dry phytomass, seed yield) in comparison with the zoned Dymkovsky variety are given. All varieties showed high winter hardiness in the conditions of the Kirov region (more than 79 %). By productivity of green mass the varieties Karmin, Trio, Stodolich (Russia) were selected. They provided significantly high productivity for 2 years of grass stand use (5.52-5.81 kg/m2, +2.01-2.30 kg/m2 to standard) and were characterized by medium value of GCA (104.2-109.6 %) and very high SCA (123.7-139.3 %). According to the total collection of dry phytomass, the best varieties were Karmin and Gefest (Russia) with a significantly high level of productivity (1.28; 1.29 kg/m2, +0.49; 0.50 kg/m2 to standard), medium GCA (102.4; 103.2 %) and very high SCA (133.3; 134.4 %). By seed yield, the most productive Russian varieties are Stodolishchensky, Trio and Svetlyachok (74.2-82.6 g/m2, +8.8-17.2 g/m2 to standard) with very high GCA (125.5-139.8 %) and SCA value of medium and high level (106.6-118.7 %). According to the results of the study, for further breeding work the following meadow clover cultivars of Russian research institutes breeding were included as components of new polycross populations: early-matured Karmin and Trio, late-matured Gefest and Svetlyachok.

Finance management is an integral part of the general system of organization management, it is considered as an object and means of strategic management, as a sum total of methods and ways, which could provide enhancement of finance sustainability and obtaining maximum profits from functioning in the interests of its owners. However, finance management as a part of organization management requires formalization in view of choosing and applying finance tools of strategic planning, where strategy of organization development is seen as goal setting that can ensure the leading positions on market. The article analyzes financial development and organization standing on the basis of finance monitoring conducted by the service of finance control. According to the authors, it could resolve a number of problems, such as development and use of methodology of assessing business value with regard to rising profit, providing full finance accounting to executives and business owners.

Introduction. The routine use of highly effective drugs that alter the course of multiple sclerosis requires careful patient selection in order to minimize the risks of possible adverse events. At present, drugs modifying the course of multiple sclerosis have been registered with different mechanisms of action. This makes it possible to implement individual selection of therapy taking into account the multifaceted pathogenesis of the disease. However, the presence of a burdened somatic anamnesis in the patient may significantly limit the choice of drugs by the attending physician. Aim: to gain experience in using ocrelizumab to treat patients with multiple sclerosis. Materials and methods. From 2018 ocrelizumab therapy was started in 52 MS patients: 32 patients with recurrent multiple sclerosis (MS) (23 with remitting multiple sclerosis (RMS) and 9 with secondary progressive MS with exacerbations) and 20 patients with primary progressive multiple sclerosis (PPMS). The drug was administered intravenously in drops with infusion in a dose of 600 mg every 6 months in a daytime regimen with an approved protocol of premedication and symptomatic therapy to prevent possible risks of adverse events. The initial dose was divided into 2 infusions of 300 mg at intervals of 2 weeks [5]. Before each infusion, detailed clinical blood analysis, biochemical blood tests, serological tests (HIV, hepatitis B and C, syphilis), and screening for tuberculosis (once a year) were necessarily repeated.The results. The achieved results clearly demonstrate high efficacy of ocrelizumab in the form of reduction of exacerbations frequency, disease activity according to MRI data and slower progression, which is compared with the data from previous OPERA I, OPERA II and ORATORIO clinical trials. After analysis of the data of dynamics of disability index according to EDSS scale there was observed stabilization in PPMS patients and a slight decrease in RMS patients. No exacerbations were registered in patients with RMS during the period of treatment, as well as no objective data on progression in patients with PPMS were noted.There is also good tolerance of therapy. However, the question remains as to how long the therapy should take into account the safety spectrum.

The article presents the results of study of promising diploid and tetraploid red clover varieties, differed by ripening time, sowed in 2016 in competitive varietal trial at two-year cutting mode of grass-stand use. In the conditions of Kirov region, there was carried out a comprehensive assessment of varieties according to the following biological and production indicators: winter hardiness, duration of growing season, plant and grass-stand height, leafiness, productivity of dry mass by cuttings and in total for two years of use, protein and fiber content, yield of raw protein and digestible protein, resistance to root rot. In each group of ripeness, the best varieties have been identified. They combined protein productivity, winter hardiness (72.3-94.0 %) and resistance to root rot: early tetraploid population SGPFT-170-2 which significantly exceeded the standard (st.) Kudesnik in the yield of raw protein by 0.49 t/ha and digestible protein by 0.355 t/ha, medium-resistant to root rot, with less root system damage compared to the standard by 5.6% in the first year of use (1 y. u.) and 3.3% in the second year of use (2 y. u.); diploid early variety GPF-54-2, which significantly exceeded st. Dymkovsky by 0.391 t/ha in the yield of raw protein in total for two years of use and showed resistance to root rot in the 1 y. u.; diploid late varieties SGP-105 and GPR-36-2, which provided significant additions to st. Kirovsky 159 in the yield of raw protein (+1.216 and +0.964 t/ha) and digestible protein (+0.918 and +0.726 t/ha), combining fodder productivity with resistance to root rot in the 1 y. u. and average resistance in the 2 y. u. (st. Kirovsky 159 is susceptible).Conflict of interest: the authors stated that there was no conflict of interest.

The paper presents a detailed algorithm for the treatment and follow-up of patients with recurrent multiple sclerosis and primary progressive multiple sclerosis in the use of ocrelizumab.

The aim of the reserch was to study the state of the cardiovascular system, systemic inflammation and balance oxidant/|antioxidant in patients with relapsing-remitting multiple sclerosis.Material and methods. The study included 45 patients with relapsing-remitting multiple sclerosis (17 men and 28 women), age 28 [24; 32] years, disease duration 5.5 [2; 7] years. The control group included practically healthy patients, age 30 [25; 33] years. Patients with multiple sclerosis were examined neurologically with Expanded Disability Disease Score rating of disability. Instrumental methods included a comprehensive assessment of the cardiovascular system (24-hour Holter ECG monitoring and 24-hour blood pressure monitoring with determination of the daily arterial vascular stiffness, echocardiography). Laboratory methods included clinical and biochemical analysis of blood, lipid profile, glycemia, C-reactive protein. The indices of oxidative stress (acylhydroperoxide) and antioxidant protection (glutathione peroxidase, superoxide dismutase) were studied; a marker of endothelial dysfunction (vascular cellular adhesion molecule-1) were researched.Results. In the group of patients with multiple sclerosis, there was an increase in C-reactive protein, the marker of endothelial dysfunction compared with the control group (p

Microcapsules consisted of biocompatible components- bovine serum albumin and tannic acid were made using Layer-by-Layer encapsulation method. Process of microcapsule formation was studied. Poly(allyl)amine hydrochloride (PAH) was included into the microcapsules and process of its release into medium with neutral and alkaline pH and trypsin was studied. The ability to control release of model substance PAH from these capsules with the help of trypsin was shown.

Introduction. Volunteering is a socially significant activity, which contributes to solving separate acute social issues and showing the best qualities of an individual – compassion, ability to sympathise and readiness to provide assistance to people in need. Through volunteering, a person achieves self-esteem and a feeling of his or her relevance and usefulness. Under the present circumstances, aspects of the study of volunteering and youth attitudes to this concept are especially relevant. Over the last decades, social transformations have occurred, leading to a reassessment of the value system, and, consequently, society has lost its moral compass. Participation in volunteering can become one of the effective factors in the formation of ethical standards and humanistic value orientations among young people.The aim of the research was to investigate the educational potential of volunteering through studying the attitudes of young people.Methodology and research methods. The research was based on axiological and sociological approaches. In the course of the research, the following methods were used: review and synthesis of historical-philosophical and sociological literature, sociological group face-to-face surveys, and comparative analysis of statistical data. Results and scientific novelty. The authors justified the necessity for moral education of working youth through the involvement of young people in realizing charitable projects and organising philanthropic events. The authors highlighted the aspects of conducting charitable activities in one of the socially-oriented enterprises of the Urals – Sinarsky Pipe Plant. A questionnaire based survey conducted among young workers of that metal manufacturer revealed the fact of mass participation in various charitable activities (out of the sample seize of 180 young workers, 89% of respondents admitted their involvement in philanthropic activities). The respondents expressed interest in charitable projects and readiness to spend own time, energy and money for rendering disinterested targeted assistance to children with special needs and children with disabilities (56.3%), to elderly people living in difficult life situations (52.5%), to stray animals (50.0%), to children suffering from cancer (49.3%). It was concluded that charity work forms ethical standards at young people, and develops altruistic qualities such as disinterestedness and responsiveness, as well as civil consciousness.Practical significance. The research outcomes can be used when preparing, organising and holding charitable work with the aim of bringing up morally and ethically educated young workers, as well as students of educational institutions of different levels.

The article provides the results of complex estimation of 11 perspective composite hybrid and poly-cross populations of red clover (Trifolium pratense L.) conducted in competitive variety trial of 2014-2016. The winter hardiness of the new varieties created by the authors, duration of growing season, plant height, number of leaves per plant, fodder production by cutting and years of use, leaves yield, and quality of dry matter (total and digestive protein yield) have been determined. Immunological estimation of the varieties by degree of development of leaf diseases and root rot was done. By complex of economic-valuable traits early populations GPF-83-2/4, GPR-41-4, GPF-122-2, GPF-49-3 and middle-ripening SGP-188 have been selected. The varieties combine high winter hardiness (93.9.100%) at the level of standards (st.) Trio and Dymkovsky, fodder production (sum yield of dry matter of early varieties - 18.27.19.88 t/ha (+1.79.3.40 t/ha to the st. Trio), middle-ripened SGP-188 - 21.3 t/ha (+2.72 t/ha to the st. Dymkovsky), of raw protein - 2.88.3.01 t/ha (+0.31.0.44 t/ha) and 3.52 t/ha (+0.62 t/ha)), fodder quality (yield of digestive protein - 2.00 .2.08 t/ha (+0.22 .0.30 t/ha) and 2.47 t/ha (+0.46 t/ha), respectively) with stable seed yield capacity (4.10.4.99 dt/ha in average for 2 years) and age plant resistance to root rots.

Acetaminophen (AAP) is one of the most common and widely used antipyretic drugs, but its overdose is the leading cause of fulminant hepatic insufficiency in the world. Mechanisms of liver damage at the use of toxic doses of AAP are caused by the transformation of the isoform of cytochrome P450 (CYP2E1, CYP2A6) into a reactive metabolite, N-acetyl-parabenzoquinonimine (NAPQI), which plays a major role in hepatotoxicity. Another mechanism of hepatotoxicity includes the formation of peroxynitrite – a toxic free radical produced in the mitochondria, which causes oxidative damage. In addition to liver damage in case of acetaminophen poisoning, nephrotoxic effect can occur. Potential mechanisms of nephrotoxicity in overdose of AAP are presented, caused by cytochrome P450, as well as prostaglandin synthetase and enzyme N-deacetylase are described. In the clinical case described by us, the development of fulminant hepatic insufficiency against the background of acetaminophen administration led to the development of a coma along with the kidney damage, however, a stable positive dynamics, was achieved during treatment. In the catamnesis 2.5 years later, there were no signs of fibrosis or cirrhosis of the liver.

Purpose. The research is aimed at understanding the philosophical and journalistic heritage of M. Scheler during 1914-1919. "The philosophy of war" is regarded as the middle link between the phenomenological and anthropological stages of its philosophical evolution. The theoretical and methodological basis of the study is the philosophical legacy of Max Scheler, as well as the work of domestic and Western researchers devoted to this issue. Problems of Weltkriegsphilosophie become comprehensible based on the historical, logical and comparative principles of historical and philosophical analysis, which allowed to theoretically reconstruct the cultural and historical context, philosophical sources and ideological intentions of the German philosopher. Originality. For the first time in domestic historical and philosophical thought, it proved that the works by Max Scheler of the First World War played an outstanding role in the formation of philosophical anthropology as a separate philosophical trend. Conclusions. The basis of the Weltkriegsphilosophie by Max Scheler is the philosophical comprehension of the war in which the thinker tries to see the high sacral meaning, where the sacrifices that the nation brings to the altar of victory are not in vain: the nation is rallying this sacrifice, its readiness for it. According to Scheler, war is the most effective means of forming the so-called "love communities", to which he refers combat brotherhood, family and nation as a "collective personality", which recognizes itself through war. The philosopher is disappointed to some part with militaristic enthusiasm in his later military journalistic works and calls for a spiritual and moral renewal of Europe, fed from Christian roots. At the heart of this renewal should be the principle of personal solidarity, based on the Christian idea of love. However, Catholic universalism is an insufficient means for the formation of a "love community" and a new man who is co-creator of God that constitutes the main core of the philosophical anthropology of Max Scheler, which emerges in the 20s of the twentieth century. Based on this, the article affirms the existence in Sheler’s works of an intermediate stage between his phenomenology and philosophical anthropology – Weltkriegsphilosophie (philosophy of the World War).

This article presents a clinical case of suboptimal response to multiple sclerosis therapy and an algorithm for treatment, taking into account the existing performance criteria.

This article presents the results of the immunological profile of CD4+ T cells and Th17 cells and production of interleukin-17 (IL-17) in two groups of patients receiving treatment natalizumab and fingolimod. The results can underpin the justification for the preferred transfer of patients with relapsing-remitting multiple sclerosis after treatment by natalizumab to fingolimod.

The article presents results of breeding activity (1990.2012) on creation of early, winter hardiness, productive red clover (Trifolium pratense L.) variety ‘Shans’ having high fodder quality. Originators of the variety - Falenki breeding station and North-East Agricultural Research Institute Variety ‘Shans’ (breeding line 804/90) created by a method of multiple biotypic selection from middle-ripening adaptive variety ‘Dymkovsky’. According to the results of competitive tests in Falenki breeding station (2008.2012), the variety had advantage over standard variety ‘Trio’ by main economic traits and distinguished with earliness (55.75 days from spring re-growth till beginning of flowering; 110.128 days for seed ripening), high winter hardiness (96.100 %), dry matter yield - 11.3 t/ha and raw protein yield - 1.53 t/ha, high seed yield - 0.2 t/ha, resistance against root rot (index of disease development IDD = 18.2 %). According to data of ecological test (2012) under agro-climatic conditions of Kirov city (North-East Agricultural Institute) variety ‘Shans’ shown high potential productivity of dry matter - 21.22 t/ha (significantly higher than standard ‘Trio’ on 2.80 t/ha or 15.2%). In 2012 the variety was passed to State varietal test, since 2017 - was included into State Register of breeding achievements allowed to use in Volga-Vyatka region (patent № 8916 from February 13, 2017).

This article presents a review of the efficacy and safety of three oral drugs for multiple sclerosis, which are registered in the Russian Federation: teriflunomide, dimethylfumarate, fingolimod.

Monoclonal antibodies are widely used in various fields of modern medicine, for example, in oncology, rheumatology, gastroenterology, transplantation. Since beginning of this century monoclonal antibodies began to be explored for the treatment of multiple sclerosis (MS). From this period monoclonal antibody also actively introduced in pathogenetic therapy of MS. In this review, we discuss the findings of clinical trials already registered monoclonal antibodies in the Russian Federation, such as Natalizumab and Alemtuzumab.

This review includes results of experimental and clinical studies of new oral drug teriflunomide for pathogenetic treatment of multiple sclerosis (MS). Given the mechanism of action, clinical data of the studies II and III phases of clinical efficacy, tolerability and safety. Discusses the place of teriflunomide in pathogenetic treatment of MS.

There was a whole series of drugs that change the course of multiple sclerosis over the past 20 years. However, a single algorithm of patients of childbearing age has yet been developed. There are new drugs more efficiently, but at the same time with high risk of pathological effects on the fetus, which requires more detail to provide algorithm of this category of patients.

Results of perennial (1991-2016) experimental work carried out in Kirov region on creation of new breeding material and varieties of red clover combining aluminum tolerance and high productivity and other valuable parameters under conditions of North-east of European Russia are presented in the article. Methods are presented of creation of breeding material with tolerance to ions of aluminum and hydrogen. Characteristic of provocative edaphic background is done. Aluminum tolerant variety Grin is created with method of multiple two-stage selection of genotypes resistant to H+ and Al3+ (in laboratory towel culture and on hard field background). The variety is included in State Register of breeding achievements of Russian Federation in 2010 for 4 regions. As a result of selection in vitro for resistance to toxic ions of aluminum and hydrogen in combination with selection on field provocative background 60 breeding lines were obtained having value for creation of aluminum- and acid-resistant varieties of red clover. High resistance is revealed to edaphic stress-factors in perspective clone population P-15: in nursery of preliminary test on aluminum acid background under drought of 2016 the population statistically exceed standard variety Dymkovsky and early variety Trio on productivity of green mass on 6.5 and 9.5 t/ha or 23.0 and 37.7%. 79 breed- ing lines were created by the method of direct selection of genotypes on hard aluminum acid field background, 20 perspective lines were chosen combining resistance to edaphic stress factors with winter hardiness and high productivity of green mass (17.5-64.1% higher than variety Grin).

The article presents the results of breeding work (1999-2015) on creation of new tetraploid variety Flamingo of hybrid clover (Thrifolium hybridum L.). The variety Flamingo (breeding population SGPG-19) was creatied in North-East Agricultural Research Institute (Kirov) and Falenki Plant-Breeding Station (Kirov region) by polycross of eight best parental forms of various eco-geographical origin selected by OCS: variety Luzhanin (North-West Agricultural Research Institute "Belogorka"), selective number R-100 (V.K. Williams All-Russian Fodder Research Institute), perspective populations SGPG-9 (selection from variety Kurtsevskiy, Archangelsk region), SGPG-11 (variety Frida, Sweden), SGPG-12 (variety Pervenets from Moscow region), SGPG-13 (Priekulskiy tetra, Lithuania), SGPG-14, SGPG-15 (North-East Agricultural Research Institute), followed by recurrent biotipical selection. As a result of perennial (2007-2015) studying in competitive variety testing of North-East Agricultural Research Institute the new variety has the advantage on standard Fregat by basic economic-valuable traits. It is early-maturing (period from spring growth till first cutting is 54-62 days; till seeds ripening - 108-123 days); has high winter hardiness (75-90%), forage productivity of 8.75 t/ha of dry matter (+6.3% to standard), protein yield of 1.04 t/ha (+9.5% to standard), seed yield of 1.17 c/ha, root rot resistance (degree of defeat 0.1-1.8 points on a five-point scale). According to date of ecological varietal testing (2013) under agro-climatic conditions of Falenki Plant-Breeding Station differ from Kirov by poor soil fertility and contrasting weather conditions in the growing season the variety Flamingo significantly surpassed standard Fregat on protein yield (0.61 t/ha) by 8.9% at protein content in dry matter of 16.75% (+2.12% to standard). In 2015 the new variety of hybrid clover Flamingo transferred to the State variety testing as recommended for hay, pasture use, as well as for creation of melliferous fields in all areas of cultivation of the crop in the Russian Federation.

In the conditions of the Kirov region, the productivity of seeds of four complex hybrid populations (SGP) of red clover was studied, including those formed against an infectious fusarium background (SGPF). The research was carried out in the nursery for evaluating the seed productivity of 2017 sowing in comparison with the standard (st.) Dymkovsky for 2 years of use (y.u.). The characteristics of the SGP and SGPF according to winter hardiness, the start of vegetation phases of development, plant height, structure of seedgrass stand, yield and quality of seed material are given. All studied varieties were more productive than the standard (1.97 c/ha). Reliably high seed yield on average for 2 years was shown by SGPF-158-3 – 2.48 c/ha, SGP-188 – 2.32 c/ha, SGPF-157-3 – 2.16 c/ha. According to fruiting indicators, in 2019SGPF-158-3 with small heads, but with the largest number of flowers and seeds (132.2 and 77.4 pcs., respectively), good seediness (58.8 %) and high seed weight per head (0.153 g) was selected. Also, high rates were noted in the populations of SGPF-157-3 and SGPF-160-3. A strong correlation between seed yield and fruiting rates was revealed: the number of flowers in the head (r = 0.92), the total number of seeds in the head (r = 0.92), the number of filled seeds in the head (r = 0.94), the seediness of the head (r = 0.90), the total weight of seeds in the head (r = 0.85), the mass of filledseeds in the head (r = 0.87). A close positive correlation was noted between the hydrothermal coefficient (HTC) value and length (r = 0.86), width (r = 0.86) of the red clover head during the intergrowth period “regrowth - the beginning of flowering”. It has been established that the average daily air temperature and the sum of effective temperatures during the “beginning of flowering - ripening” period have a positive effect on the fruiting performance: “seediness of the heads” (r = 0.97 and r = 0.87) and “the number of seeds in the head” (r = 0.95 and r = 0.89, respectively). In the same interphase period, a close negative dependence of the indicated fruiting indices on the HTC values was revealed (r = -0.95 and r = -0.94). The sowing qualities of the seeds of the 2019 harvest were determined; it was found that all seed material corresponds to the category of “original and elite seeds”. As the result of the research, the populations of red clover SGPF-158-3, SGP-188 and SGPF-157-3, superior to st. Dymkovsky on seed productivity (by 0.51; 0.35 and 0.9 c/ha, respectively, LSD05 = 0.12 c/ha) and fruiting indicators, were selected.

Dimethyl fumarate (DMF) is dimethyl ester of fumaric acid, a naturally occurring molecule that plays a key role in redox processes of tissue respiration. Results of studies on animal models demonstrate that the drug has an anti-inflammatory and cytoprotective action. Anti-inflammatory effects of DMF could be mediated by several mechanisms, including inhibition of nuclear factor-kappaB-dependent transcription and suppression of cytokine production and cell adhesion molecule expression. 2 years after start of treatment DMF significantly increased the relative number of patients without active disease by clinical, radiological and general criteria in comparison with the placebo group. According to the DEFINE trial, the proportion of patients without active disease in twice daily DMF group was 28% (vs placebo, p = 0,012), and 18% (vs placebo, p < 0, 0001) according to the CONFIRM trial. DMF demonstrated similar efficacy in various subgroups of patients classified according to baseline characteristics of the disease, including frequency of relapses in the past, pre-treatment, level of disability, as well as type and extent of the lesions. In terms of safety profile, DMF was similar to GA and placebo. Adverse effects on the gastrointestinal tract against the background of DMF were mild or moderate, transient and treatable. Administration of DMF did not increase the risk of infections and malignancies.

Multiple sclerosis (MS) is an immune-mediated chronic inflammatory disorder of the central nervous system (CNS) often causing disability in young adults. As is the case with the majority of autoimmune diseases, multiple sclerosis patients are predominantly women - 2.5 times more often than men. [1-4, 13] Considering the fact that the disease onset mainly occurs in childbearing age, it becomes clear why so much attention has been recently given to the possibility of pregnancy for patients with multiple sclerosis.

13 patients from the Moscow Multiple Sclerosis Center with remitting MS and not responsive to treatment with 1st line DMD were given Fingolimod (Gilenya) starting from January 2012. After one year of therapy, the group demonstrated a significant decrease in the frequency of exacerbations from 2,54 ± 0,97 to 0,15 ± 0,38 (p ≤ 0,0001) per year, and showed no disability progression according to EDSS. Other results were good tolerability and safety of therapy, no clinically relevant deviations in hematological state, no ophthalmic complications. In view of the possible risk of transient bradycardia, before starting fingolimid therapy MS patients were examined, and their heart was monitored for 6 hours after they were given first dose. The monitoring registered a decrease in heart rate within permissible range (not requiring medical intervention) in 30.76% of cases at 34th hour, and by 6th hour the heart rate returned to the baseline value.