[An overview of investments in the development of the Russian Medtech market and the prospects for the impact of digitalization in medicine on the economic performance of companies until 2030].

Today, the topic of digitalization, the introduction of innovations based on Big Data, the complexity of technologies due to the introduction of artificial intelligence in medicine and healthcare is one of the most relevant in this industry, undoubtedly contributing to its rapid development. As a result of this development, there is a huge number of services and applications. Internet resources, not only for health tracking (more than 3,500 applications are available by the end of 2023), but also the development of diagnostic resources, telemedicine, etc. Quite quickly, it was the pandemic and its consequences that changed the format of interaction between doctors, communication in the community of doctors, and their interaction with patients. Saving time when making an appointment with a doctor, visiting him, constant monitoring of the condition of patients, becoming better and more multidirectional day by day, make it possible to provide timely, relevant care to more people. The use of artificial intelligence technologies and digital solutions in the field of Russian healthcare opens up great prospects for both doctors and patients, as well as for many government agencies, since the development of regulatory and legal regulation and state control and management of innovations in the field of medicine and healthcare is important. An important factor is that not only government programs for the development of healthcare, but also investments are extremely important for the development of digital medicine.

[The marketing analysis of plastic surgery market in Russia].

The article presents analytical review and marketing analysis of the market of plastic surgery in Russia. The characteristics of the segment of plastic surgery services in National and regional markets of fee-for-service medicine in 2016-2019 are given, including characteristics of consumer behavior in this segment. The information was obtained by comprehensive analysis of data from plastic surgery clinics, review of opinions of leading market experts, as well as through study of consumer behavior of Russian customers of medical services. Particular attention is attended to peculiarities of development of market of private plastic medicine in conditions of incipient way out of country of economic crisis. The review includes evaluation of dynamics of private medicine market in Russia and its individual segments since 2015. The study includes detailed description of segment of plastic surgery services of the Russian market of fee-for-service medicine. The first-rate players in the segment are marked out in terms of revenue and number of medical institutions in national and regional market. The review also includes description of consumer behavior in the segment of plastic surgery services. The most required services are identified. The average consumer costs of these services were estimated, as well as the consumer cost of this type of medical services in the last three years was assessed.

Role of Glutathione-S-Transferase Family Genes in Male Infertility.

Polymorphisms of xenobiotic detoxification genes GSTT1 and GSTM1 and activity of glutathione system enzymes were studied in men with infertility. The frequency of deletion variant of GSTT1 gene in men with infertility was by 2 times higher than in fertile men. Deletion variant of GSTM1 gene was 1.4-fold more frequent in infertile men than in fertile men. Complete deletion of two genes was found in 19% men with infertility and only in 6% fertile men. The balance of activity of glutathione system enzymes essential for the effective detoxification of exogenous xenobiotics and toxic endogenous metabolites was impaired in infertile carriers of deletion variants of genes. Our results suggest that adaptation mechanisms are disordered in infertile men.

Features of Lipoperoxidation, Antioxidant Defense, and Thiol/Disulfide System in the Pathogenesis of Infertility in Males, Carriers of Nonfunctional Variants of GSTT1 and GSTM1 Gene Polymorphisms.

Comparative analysis of the parameters of LPO, antioxidant defense (AOD), and the thiol/disulfide system was performed in fertile and infertile males of reproductive age carrying different genotypes of the glutathione system genes. Blood plasma, blood hemolysate, and ejaculate served as specimens for biochemical studies. A decrease in glutathione S-transferase activity was found in blood and ejaculate specimens from fertile and infertile carriers of nonfunctional GSTT1(0/0)/GSTM1(0/0) genotypes. In infertile carriers of nonfunctional GSTT1(0/0)/GSTM1(0/0) genotypes determining reduced glutathione S-transferase activity, a decrease in the concentration of low-molecular-weight cell antioxidant (reduced glutathione) and an increase in the concentration of secondary LPO products (TBA-reactive substances) were revealed. Identification of carriers the polymorphic GSTT1 and GSTM1 variants and analysis of activity of the thiol/disulfide system enzymes can be recommended for additional evaluation of the risk for reproductive dysfunction in men.

Effect of Preparation Based on Trametes Pubescens Xylotroph Fungi on Lipid Peroxidation in the Blood of Experimental Animals under Conditions of Dark Stress.

Using the model of dark stress caused by animal maintenance at dimmed light we showed that Trametin (product obtained during liquid-phase culturing of Trametes pubescens xylotroph fungi) effectively prevented oxidative stress under conditions of light deprivation. The preparation increased the level of unsaturation of lipids, reduced the concentration of primary and end-products of LPO, and increases both the integral parameter of the antioxidant defense system (total antioxidant activity) and its components (activity of superoxide dismutase and reduced glutathione).

[Russian experience of lacosamide (vimpat) usage in treatment of uncontrolled focal epilepsy]. / Rossiiskii opyt primeneniya lakosamida (vimpat) pri lechenii patsientov s nekontroliruemoi fokal'noi epilepsiei.

Many patients with epilepsy receive treatment in polytherapy. Selection of antiepileptic drugs (AEDs) for the combination should be carried out in accordance with the principles of rational polytherapy, taking into account the mechanism of action, pharmacokinetic (PK) and pharmacodynamic (PD) properties of drugs. Along with levetiracetam, gabapentin, vigabatrin and pregabalin, lacosamide (LCM) shows superior PK profile in rating of all AED and can be combined with any of them. The goal of this study was to evaluate efficacy and tolerability of LCM in patients with uncontrolled partial onset seizures (POS) in routine clinical practice. METHODS: 181 patient's charts from 14 sites in Russia have been analyzed in retrospective manner. Patients 16 years old and older with POS with or without secondary generalization were included. Documented observation period of up to 12 months after initiation or until discontinuation of LCM therapy. Primary effectiveness variables was retention at Observational Point 3 (approximately 12 months). Other variables were: percentage change from historical baseline in seizure frequency, 50% and 75% treatment response and seizure-free status at the Observational Points 1, 2 and 3 (approximately 3, 6 and 12 months) and incidence and reason of treatment discontinuation. RESULTS: retention rate was high with 89.5% after 12-month observation. The development of seizure frequency showed a continuous decrease in terms of 50%, 75% treatment respond rates and seizure free status. A total of 5 adverse drug reactions leading to discontinuation of LCM therapy were recorded in 5 of 181 patients (2.8%) during the observation period. The high retention rate observed in this retrospective chart review is assumed to indicate a good tolerability and effectiveness of an adjunctive LCM treatment in patients with uncontrolled partial epilepsy in Russia.

Hepatitis C virus: The role of N-glycosylation sites of viral genotype 1b proteins for formation of viral particles in insect and mammalian cells.

Hepatitis C virus (HCV) is characterized by considerable genetic variability and, as a consequence, it has 6 genotypes and multitude of subtypes. HCV envelope glycoproteins are involved in the virion formation; the correct folding of these proteins plays the key role in virus infectivity. Glycosylation at certain sites of different genotypes HCV glycoproteins shows substantial differences in functions of the individual glycans (Goffard et al., 2005; Helle et al., 2010) [1], [2]. In this study, differential glycosylation sites of HCV genotype 1b envelope proteins in insect and mammalian cells was demonstrated. We showed that part of glycosylation sites was important for folding of the proteins involved in the formation of viral particles. Point mutations were introduced in the protein N-glycosylation sites of HCV (genotype 1b) and the mutant proteins were analyzed using baculovirus expression system in mammalian and insect cells. Our data showed that, in contrast to HCV 1a and 2a, the folding of HCV 1b envelope proteins E2 (sites N1, N2, N10) and E1 (sites N1, N5) was disrupted, however that did not prevent the formation of virus-like particles (VLP) with misfolded glycoproteins having densities typical for HCV particles containing RNA fragments. Experimental data are supported by mathematical modeling of the structure of E1 mutant variants.

Mitochondrial energy-dissipating systems (alternative oxidase, uncoupling proteins, and external NADH dehydrogenase) are involved in development of frost-resistance of winter wheat seedlings.

Gene expression, protein synthesis, and activities of alternative oxidase (AOX), uncoupling proteins (UCP), adenine nucleotide translocator (ANT), and non-coupled NAD(P)H dehydrogenases (NDex, NDPex, and NDin) were studied in shoots of etiolated winter wheat (Triticum aestivum L.) seedlings after exposure to hardening low positive (2°C for 7 days) and freezing (-2°C for 2 days) temperatures. The cold hardening efficiently increased frost-resistance of the seedlings and decreased the generation of reactive oxygen species (ROS) during further cold shock. Functioning of mitochondrial energy-dissipating systems can represent a mechanism responsible for the decrease in ROS under these conditions. These systems are different in their response to the action of the hardening low positive and freezing temperatures. The functioning of the first system causes induction of AOX and UCP synthesis associated with an increase in electron transfer via AOX in the mitochondrial respiratory chain and also with an increase in the sensitivity of mitochondrial non-phosphorylating respiration to linoleic and palmitic acids. The increase in electron transfer via AOX upon exposure of seedlings to hardening freezing temperature is associated with retention of a high activity of NDex. It seems that NDex but not the NDPex and NDin can play an important role in maintaining the functional state of mitochondria in heterotrophic tissues of plants under the influence of freezing temperatures. The involvement of the mitochondrial energy-dissipating systems and their possible physiological role in the adaptation of winter crops to cold and frost are discussed.

[Focal features of idiopathic generalized epilepsy].

Idiopathic generalized epilepsies (IGE), in some cases, have focal features in the kinematic of seizures and in the EEG. The aim of the paper was to study these clinical phenomena using video-EEG monitoring. We studied 180 patients (80 men and 100 women) with different forms of IGE with epileptic seizures recorded with this method. The effect of the "superposition" of focal electro-clinical features on the kinematic matrix and EEG pattern of the generalized myo- (clonic)-tonic-clonic seizures was noted. The authors suggest to discuss the definition of the "phenomenon of secondary focalization". This is the clinical/electroencephalographic phenomenon developed in IGE and presented by the appearance of secondary focal features (clinical and electroencephalographic) in the structure of the generalized epileptic seizure. The evidence for the secondary generalization of the seizure with the presence of the regional cortical ictogenic source as well as the diagnosis of focal epilepsy are the exclusion criteria for the phenomenon of secondary focalization.

[Side-effects of antiepileptic treatment: the current state of the problem].

The current treatment of epilepsy is directed not only at the control of seizures and comorbid states but at the improvement of quality of life and destigmatization that is the key strategic direction. The basis of treatment of epilepsy is a long-term regular taking of antiepileptic drugs (AED). However, it has been shown that quality of life of patients depends not only on clinical presentations of the disease, including seizures and higher mental functions, but on the tolerability of AED. The safety of these drugs becomes the most important component of the treatment even compared to the control of seizures. Therefore, tolerability and compliance (a patient's adherence to a recommended course of treatment, common understanding between a doctor and a patient as well as his/her relatives) receive special attention. The timed detection and correction of side-effects is an integral component of treatment of epilepsy. In some cases, the presence of rare seizures with minimal clinical presentations and even more frequent seizures that are not danger for a patient seems to be more appropriate than the increase in the number and doses of AED reducing quality of life. The balance between therapeutic and toxic effects of AED is a key issue of treatment of epilepsy.

[Character of brain interhemispheric relation in children at forming labile arterial hypertension].

Electroencephalography investigations were carried out twice in 26 schoolchildren in the age of 7-8 years and in the age of 9-10 years. The control group included healthy children: the research group included children in whom in the age of 7-8 years the normal level of arterial pressure was registered, and in whom in the age of 9-10 years labile arterial hypertension was revealed. It is revealed, that in children of younger school age forming of the labile form of arterial hypertension is connected whit infringement of processes of age changes of intercortical and cortical-subcortical interrelations and forming of rigidly integrated system of interhemispheric relations. Its mechanism of realization is carried out due to hyperactivation of the right hemisphere and it is incorporated on preclinical stage.

[Baculovirus vectors for efficient gene delivery and expression in mammalian cells].

Baculovirus expression vectors are extensively used for the delivering foreign genes and expression of recombinant proteins in insect and mammalian cells. Modified baculoviruses containing mammalian promoter elements (BacMam viruses) for an efficient transient and stable transduction of diverse mammalian cells prove a high level of heterologous proteins' expression both in vitro and in vivo. Recombinant baculovirus vectors containing mammalian expression cassette with cytomegalovirus promoter, green or red fluorescent protein gene, polyadenylate signal SV40pA, and polylinker MCS were constructed for the delivery of genes encoding hepatitis C virus structural proteins into mammalian cells. In Hek293T and Huh7 cells formation of glycoprotein complexes and HCV-like particles was observed. A high efficiency of the baculovirus-mediated gene transfer and expression of the virus envelope proteins in mammalian cells was demonstrated with using fluorescence, flow cytometry and immunoblot techniques.

[Modern principles of epilepsy therapy].

Long regular use of antiepileptic drugs (AED) aimed at reducing frequency of seizures or stopping them completely without any significant side-effects is a main principle of epilepsy treatment. The main attention is drawn to the issues of tolerability of antiepileptic therapy and compliancy, mutual understanding between a physician and a patient as well as relatives and other significant persons. The timely detection and correction of side-effects is integral part of epilepsy treatment. Currently, the attention is focused on quality of life of patients with epilepsy including physical and mental health, education, social and psychological functioning. In some cases, the occurrence of rare seizures with minimal clinical presentation or even more frequent seizures which are not dangerous to a patient is less harmful than decreasing of quality of life due to the effect of larger AED number or dose. The balance between AED therapeutic and toxic effects is a main question in epilepsy therapy. Pharmacotherapy of epilepsy requires deep knowledge of AED: spectrum of therapeutic efficacy and extent of drug effect; safety, tolerability and side-effects, in particular severe and life-threatening ones, specifics of pharmacokinetics, pharmacodynamics, between-drug interactions and mechanisms of action; titration rate, necessity in laboratory tests during treatment, peculiarities of application of pharmacoeconomics. The present review addresses modern aspects of epilepsy therapy.

[Characterization of hepatitis C virus structural proteins and HCV-like particles produced in recombinant baculovirus infected insect cells].

Three proteins, namely: "core" protein C and glycoproteins E1 and E2, are main structural proteins forming a hepatitis C vius (HCV) virion. The virus structure and assembly, a role of the structural proteins in virion morphogenesis remain unknown because of the lack of an efficient culture system for HCV to be grown in vitro. Using recombinant baculoviruses expressing HCV structural protein genes in insect cells the specific structural proteins at the level of 25-35% relative to a common cell protein content, heterodimers of the glcoproteins, and HCV-like particles have been obtained. It has been demonstrated that recombinant proteins C, E1, and E2 go through the posttranslation modification, the glycoproteins form the non-covalent heterodimer, and HCV-like particles are located in endoplasmatic reticulum membrains of infected cells. An ability of the expressed proteins for forming E1E2 dimers and HCV-like particles was used for studying the role of E1 protein glcosylation upon expression and processing of the glycoproteins.

[Hemoblastosis and leukemia morbidity in the townsfolk of Seversk and of Siberian group of chemical enterprises personnel].

Hemoblastosis and leukemia morbidity has been analyzed in the townsfolk of Seversk (in particular, Seversk residents and Siberian Group of Chemical Enterprises (SGCE) personnel). The standardized relative risk ratios for hemoblastosis morbidity in menes and womens of Seversk were found to be significantly higher in comparison with the regional standard ratios (in 1.8 and 1.5 times correspondingly). Hemoblastosis and leukemia morbidity rate in SGCE males is significantly higher in comparison with the similar regional standard ratios. Leukemia morbidity dependence due to cumulative external gamma-radiation in a dose range up to 1 Sv has not been found in SGCE personnel, without regard to chronic lymphatic leukemia.

[Surgical treatment for respiratory organ fistulas].

The paper pools the experience accumulated since 1965 at the Russian Surgery Research Center, Russian Academy of Medical Science, in treating 185 patients with respiratory organ fistulas. Medical and surgical treatments were performed in 23 and 162 patients, respectively. Radical operations were made in 124 patients, palliative ones in 38. The radical operation is to disconnect organs, by suturing the fistulous opening. If there were irreversible changes in the organs, their resection was simultaneously made. Palliative operations were performed as an auxiliary intervention before or during a radical operation. A palliative operation as an independent intervention was made only in a patient's severe general condition or in purulent fistulous complications. The findings suggest that radical surgery is the method of choice in the treatment of patients with respiratory organ fistulas.