Search

A 36-year-old man presented to the clinic with frequent headaches and a brief episode of fainting. He said that he had experienced headache for a few months and occasionally had found his arterial pressure to be elevated at 180/120 mm Hg. He sometimes felt feverish and shivering all over, which was

Choriocarcinoma (CC) is a very rare and aggressive neoplasm. The characteristic feature of this disease is a rapid hematogenous spread, mainly to the lungs and brain, which largely defines clinical signs of the disease and complicates the diagnosis. Gastrointestinal metastases are rare, and of those, only few cases with gastric location have been reported. There are publications describing choriocarcinoma syndrome (CCS). As a rule, it presents in patients with an advanced disease and is characterized by hemorrhage from metastatic foci, leading to hemoptysis and gastrointestinal bleeding. CCS development is associated with poor prognosis and high mortality. This article describes a case of testicular CC with rare few gastric metastases, complicated by CCS.

Objective: To compose a portrait of a typical consumer for various optional lines of equipping a high- speed platform car (“smart” car) with an on-board telemetry system. Methods: The means and methods of marketing, rolling questioning, statistical processing of information, comparison, general systems theory, systemic and economic analyzes, logistics, terminology, visualization are used. Results: Optional lines have been developed for each variant of the technical design of the car, based on the results of processing the questionnaires of the respondents, a portrait of a typical consumer has been compiled; some recommendations on the composition of options in each version of the high-speed platform have been made. Practical importance: The results obtained can be applied when entering the market in terms of establishing optional lines for the design of a high-speed platform and cost. Further research should be aimed at a more detailed study of market segments with the development of the best price and functional-option solutions for the final target consumer.

Introduction: Cardiac pacing is indicated for sick sinus syndrome. It is performed with a pacemaker via electrodes implanted in the heart. This technique has several disadvantages. The search for alternative methods of cardiac pacing is underway. One of them is control of heart rhythm through stimulation of the tragus. Objective: To perform the reflex stimulation of the sinoatrial node and to study the influence of the SS-68 substance on it. Materials and methods: Two electrodes were fixed in the reflexogenic zone of rabbits’ auricles, volleys of electrical impulses from an electrical stimulator were applied to the electrodes, and the synchronization range of volley frequency and cardiac contractions was recorded. This range was re-recorded again after injecting the SS-68 substance (2-phenyl-1-(3-pyrrolidine-1-cyclopropyl)-1H-indole hydrochloride) intravenously at a dose of 50 µg/kg. In other experiments on frogs in a high-frequency electromagnetic field, the process of excitation of the area of the medulla oblongata associated with the heart rhythm was visualized. After the application of SS-68 (50 μM) to the surface of this zone, the process of its excitation was recorded. Results and discussion: Stimulation of the auricular reflexogenic zone of rabbits produced a synchronization of volley frequency and heart rate in the range from 173.5 ± 2.0 to 214.0 ± 1.8 per minute. SS-68 extended this range from 168.2 ± 1.9 to 219.4 ± 1.5 per minute. In the frog’s medulla oblongata, an area synchronous to the heart rhythm glowed in the high-frequency electromagnetic field. SS-68 increased the area of glow by 131.0%. Conclusion: The substance SS-68 increases the frequency range of heart rhythm control by activating reflex stimulation of the sinoatrial node. The main point of application of SS-68 is the medulla oblongata. Glow in the high-frequency electromagnetic field reflects the process of neuron excitation. The increase in the glow zone under the influence of SS-68 indicates synchronously excited neurons, which leads to the assimilation of the central heart rhythm generation by the sinoatrial node.

The purpose of the study is to characterize the laboratory equipment of a new generation that meets the requirements that are imposed today on the training of specialists in the rolling stock of railways. Analytical, diagnostic and didactic methods, theory and methodology of design and mechanics of freight wagon, theory of complex systems, systems engineering, modeling, as well as methodological tools for organizing experiments were used. The scientific novelty is the constructive and technological scheme of a specialized laboratory stand; a didactic set of materials for organizing laboratory work using this stand.It has been established that the introduction of a new rolling stock with an increased carrying capacity is the main trend of modern car building and should be accompanied by appropriate training of highly qualified specialists capable of further development of new generation freight wagons. It is noted that conducting educational and research sessions involves studying not only the problems of strength, but also acquiring skills in working with digital technologies for collecting and transmitting data. A detailed description is given of a specialized stand developed at the Department of "Wagons and Carriage Facilities" of PGUPS for studying the properties of dynamics and strength of freight wagons of the laboratory stand. In particular, the device of the base trolley model 18-9855 is shown, the technology of the stand operation is described, illustrative materials are given on the structure and principle of operation of the projected stand. For practical laboratory exercises, a typical version of laboratory work with the use of this stand is proposed. It is shown that the involvement of students in the implementation of practical experiments and applied bench research increases interest in the future profession and allows the formation of strong skills in practical diagnostics of the current state of a freight wagon.

Introduction. Human papillomavirus (HPV) of high carcinogenic risk (HCR), in addition to being the etiological agent of cervical cancer, also contribute to development of cancer of the anus, vagina, penis, vulva and oropharyngeal cancer. In this connection, further study of the biological properties of this agent and its prevalence in different populations is an urgent task. The aim of the study was to examine the prevalence of HCR HPV in three anatomical loci in men stratified by HIV (human immunodeficiency virus) infection status (negative, HIV+/positive/HIV–) as well as by sexual behavior: men who have sex with men (MSM), heterosexual men (HM). Material and methods. The study included 256 men from Moscow and Moscow region: 73 МSМ/HIV+, 66 МSМ/ HIV–, 58 HM/HIV+, and 59 HM/HIV–. All men were tested for 14 HCR genotypes of HPV (16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66, and 68). Smears were taken from three anatomical loci: urethra, anus, oropharynx. Testing was preformed using real-time polymerase chain reaction assay (PCR-RT). Results. The highest prevalence of HCR HPV detection, regardless of the locus, was recorded for МSМ/HIV+ (82.2%), and the lowest for HM/HIV (20.3%). The highest detection of HCR HPV in scrapings of epithelial cells from anus was recorded for МSМ/HIV+ (79.5%). The highest incidence of this pathogen in oropharynx also was registered for МSМ/HIV+ (13.7%). The highest incidence of HCR HPV in scrapings of epithelial cells from urethra was recorded for HM/HIV+ (24%). The prevalence of HCR HPV among men was found to differ markedly depending on the anatomical locus, HIV status and sexual behavior. Discussion. For the first time, there were obtained data on the prevalence of HCR HPV in men with different patterns of sexual behavior and HIV status in the Moscow region. Conclusion. Screening for HCR HPV in male population based on the identification of 14 genotypes of the virus in three anatomical loci (urethra, oropharynx, anus) by PCR-RT will provide the information necessary to improve the system of epidemiological monitoring and proper planning of preventive measures among men with any risk factors for HPV persistence (presence of HIV infection and/or belonging to the MSM group). HPV screening algorithm development is required for men considering their HIV status and sexual behavior. We recommend testing for 14 HCR HPV genotypes in three loci (urethra, anus, oropharynx).

In a volatile economy and globalism, the role of the industry university is being transformed into the competence to integrate new business components inherent in ecosystems. The specificity of the evolution of the ecosystem of a transport university in the context of the transformation of the business paradigm is considered. The object of research is the ecosystem of the university.Methods of systems theory, theory of synergetics, systems analysis and synthesis were used. The materials of the official sites, the current data of the rankings of universities, as well as approaches to the creation of university ecosystems have been analyzed. The main properties and stages of development of the ecosystem of the transport university have been established.The positioning of a modern higher education institution determines the shift of the development paradigm towards the formation of an ecosystem based on the knowledge economy. A transport university, like any third-generation university, has such attributes of a business model based on an ecosystem approach as: synergy and transparency of interaction, decentralization and self-organization. The concept of the university ecosystem is proposed as an innovative format for its development in the management of spatial, personnel, social and technological development of railway transport in Russia, in response to the challenges of the national economy.The results of the study will contribute to the selection by Russian universities of the most effective business models of management in scientific and educational ecosystems, as well as the trajectories of staged development. A promising direction can be the study of the specifics of management in ecosystems not only of industrial universities, but also of network, federal higher educational institutions, as well as universities with a special research status.

Social isolation during the pandemic has exacerbated the problems of psychological support for families with a child with sensory impairments. The problem of analyzing the role of parents in correcting the development of children with disabilities, in particular, with sensory impairments, is examined from the standpoint of their functional responsibilities, but the actual state of affairs, in particular, the choice of reaction and adaptation strategies of the parents in families with such children, taking into account modern technological possibilities of correcting the health status of the children themselves. The article presents the generalized results of a study of coping behavior of parents in families with children with hearing impairments, conducted in 2018-2021 on the basis of the St. Petersburg State Public Healthcare Institution "Children's City Surdological Center". The problems that parents face when choosing strategies and models of coping behavior are systematized and are presented from the point of view of the psychological analysis of the social attitude toward the role and status of a child within a family.

Objective: To analyze special features of block trains and container trains promotion in the terminal network of the Saint Petersburg hub, in the environment of the discussed transport hub. Methods: The means and methods of the theory of warehouse systems developed by O. B. Malikov, general systems theory, system and economic analysis, logistics, and railways operational management have been applied. Results: It has been established that in order to attract transit cargo flows and further develop international transport corridors passing through the Saint Petersburg hub, primarily East–West directions, it is necessary to create a network of container terminals with flexible logistics. This solution will expand the range of delivery areas using block trains, form competitive through rates, reorient highly profitable freight traffic from road transport to railways, as well as organize interaction with European and Chinese intermodal and stevedore slotting operators and expand the operation areas block trains, container trains, express and specialized trains. Practical importance: The results obtained can be applied in the implementation of the Saint Petersburg transport hub development concept, in the design of railway hub individual elements and units, as well as in the servicing optimization of the seaport and terminal infrastructure.

One of the urgent tasks in the process of drug development is to obtain stable pharmaceutical products in the process of storage and use. To establish the expiration date, it is necessary to determine the time during which the developed drug is able to maintain stability and meet all the requirements stated in the regulatory documentation. The aim of the study was to study the stability of laboratory samples of wound healing gel with cycvalone during long-term storage in natural conditions. The developed composition of the wound healing gel includes the antioxidant agent cycvalone, which has a pronounced manifestation of antioxidant and anti-radical activity, as well as has a wound healing, immunotropic and anti-inflammatory effect. Carbomer (Carbopol-940), potassium hydroxide solution and purified water were used as excipients. Gel samples were stored in the primary packaging at room temperature in a place protected from light. The stability of the dosage form was studied according to the following parameters: description, pH of water extraction, authenticity, colloidal and thermal stability, quantitative determination, rheological parameters in accordance with the developed methods. The measurement was performed on 6 series of dosage forms: after preparation, after 6, 12, 18 and 24 months of storage in vivo. The results of determining the quality indicators of the wound healing gel with an antioxidant agent (cycvalone) indicate a rational selection of active and auxiliary substances and their concentration, the choice of a rational technology and the absence of interaction between the components of the developed dosage form. Based on the conducted studies, it is proved that the wound healing gel with cycvalone remains stable during storage at a temperature of 15 to 25 ˚С for 24 months.

The relevance of the study is determined by the fact that today at the test site of the Northern Railway, client-oriented priorities are being actively implemented and measures are being taken to attract new customers to the network, which will increase the share of highly profitable cargo and loading volumes in general, as well as the volume of cargo operations at stations.An attempt was made to propose a change in technology and increase the throughput on the Solombalka – Karpogory section from five to ten pairs of trains per day, based on an assessment of the prospective volumes of work associated with the development of stations in the region and the operating costs associated with their operation.The current state of cargo and commercial operations in the Arkhangelsk region of the Northern Railway was considered, and the prospects for the development of cargo operations were identified.The subject of research is loading stations. The object of the study is the Arkhangelsk territorial administration of the Northern Railway — a branch of JSC Russian Railways.Methods of system analysis, observation method, statistical method, forecasting and predictive modeling are applied.A feasibility study for changing technology and increasing throughput on the Arkhangelsk city – Karpogory section has been carried out. The economic efficiency of the proposal has been confirmed. The research carried out is the result of a two-year interaction with the Northern Railway. The research elements have already been introduced at the Northern Railway test site.

Concerning the uncontrolled growth in the incidence of obesity and Type 2 Diabetes Mellitus (T2DM), numerous research have been carried out to study the pathogenetic mechanisms of progress of these diseases and development of new methods for their prevention and treatment in recent years. T2DM is known to be a multifactorial disease, in the development of which both lifestyle and various environmental factors, and genetic predisposition are involved. At the same time, in recent years, a theory has been discussed that intestinal dysbiosis, which is caused with quantitative and qualitative changes in the gut microbiota (GM) is one of the mechanisms of obesity and T2DM development. At the moment, various methods have been proposed for restoring the normal composition of GM, including the administration of prebiotics and metabiotics that stimulate the growth of gut flora, as well as probiotics, which directly include the necessary beneficial bacteria (mainly Bifidobacterium and Lactobacillus). Fecal microflora transplantation (FMT), which allows transferring an entire microbial community into the recipient's body, rather than individual bacteria is the newest and least studied method of GM normalization. In this connection, this method of GM influencing is of great interest for the prevention and treatment of metabolic diseases.

At the beginning of the XXI century, with the advent of technical capabilities and new methods of genes sequencing, the attention of researchers to the study of the human metagenome has significantly increased. The interaction between changes in the qualitative and quantitative composition of the gut microbiota (GM) and various diseases is being actively studied, a search for specific metabolites and genes of microorganisms that may be associated with the development, in particular, of immune-mediated diseases is underway. In recent years, a lot of new data have been published on the possible contribution of gut flora dysbiosis to the development of Type 1 Diabetes Mellitus (T1DM), while the first assumptions were put forward as far back as 1970s. The search for pathogenetic mechanisms of GM influence on the development and progression of T1DM is becoming an increasingly relevant objective, since in recent years the incidence of T1DM is rapidly increasing, which is a serious health problem throughout the world.This review discusses the current ideas about the role of GM in the immunopathogenesis of T1DM, new data on the near-term prospects in the study of the human macrogenome, current ideas about the role of GM in the immunopathogenesis of T1DM, and the possibility of applying this knowledge by the practitioner.

Prolonged subfebrile condition (PSC) is a complex diagnostic and therapeutic problem caused by a wide variety of reasons, which often require a wide and expensive examination, consultations of various specialists, and repeated hospitalizations. Most often, PSC is associated with infections, some non-infectious diseases (predominantly connective tissue) and growths. To infectious causes of DS include: acute respiratory viral infections, herpes virus infections, toxoplasmosis, chlamydia, borreliosis, bartonellosis, etc. Separately, “psychogenic fevers”, subfebrile condition associated with taking drugs, and artifical subfebrile condition are distinguished. The condition of the children, as a rule, is benign and in most cases goes away on their own within 6-24 months.

In this article, we report a case of progressive multifocal leukoencephalopathy in an HIV-infected patient receiving antiretroviral therapy. The case is interesting because of its favorable outcome despite severe clinical manifestations of the disease. Key words: HIV infection, case report, progressive multifocal leukoencephalopathy

Purpose. Evaluate the stability of the rocks surrounding the roadways in a coal-rock stratum, taking into account the deformation characteristics of supporting structures. Methodology. To achieve this goal laboratory study of the deformation characteristics of supporting structures located between the simulated roof and floor of the coal seam under uniaxial compression was performed. Results. This study demonstrates that the deformation characteristics of secondary support structures affect the stability of roadway surrounding rocks in a coal-rock stratum. The nature of the deformation of supporting structures under the action of external forces is specified by their stiffness. All other things being equal, when the roof and floor rocks have a constant flexural rigidity, their stability depends on the stiffness of the supporting structures and the direction of the load applied in the tangential (wooden crib supports: 4-point chock, sandwich chock) or radial (vertical timber sets) direction. For the simulated supporting structures with an increase in the compressive load was recorded a simultaneous linear increase in their stiffness and deformation modulus. Moreover, for wooden yielding crib supports, when the load is applying across the wood fibres, the compressed chocks of wooden cribs are compacted, because of which the roof-to-floor convergence is limited. There is no such pattern for rigid structures in the form of vertical timber sets. After the loss of stability of the supporting structure, the deformation modulus decreases, which is accompanied by an increase in the roof-to-floor convergence to the destruction of the construction. It is recommended to refuse to use rigid and fragile secondary support structures. Novelty. The roadways roof stability in the coal-rock stratum is estimated by the maximum relative deformation of the secondary support structures under uniaxial compression using a coefficient characterizing the ratio of the stiffness of the working supporting structure to flexural rigidity of the roof and floor strata. Practical significance. It is necessary to focus on the use of yielding supporting structures to ensure the stability of the immediate roof and floor of mine workings in the coal-rock stratum and the operational condition of the gateroads adjacent to the working face at the extraction site of the coal mine.

The aim of the study: to analyze the prevalence of resistance mutations to elsulfavirine and to evaluate the effectiveness of it among HIV-infected treatment-naïve patients in real clinical practice.Materials and methods. The study included 578 patients with HIV infection, which divided into 3 groups. The first group is 354 HIV-infected treatment-naïve patients for whom HIV-1 nucleotide sequences were obtained as part of routine drug resistance testing. The second study group included 111 HIV-infected treatment-naïve patients, tested for drug resistance before the antiretroviral therapy containing elsulfavirine. The third study group included 113 HIV-infected treatment-naïve patients, each of whom was assigned a treatment regimen containing elsulfavirine without prior drug resistance testing. The observation period for patients of the second and third groups who received treatment was 24 weeks. To assess the effectiveness of antiretroviral therapy in patients, viral load, CD4+ T-cell counts, and adherence to therapy were assessed. HIV-1 subtypes and drug resistance mutations were determined using the Stanford HIV Resistance Database (v. 8.9-1). To clarify the results of subtyping, phylogenetic analysis of nucleotide sequences was carried out using the MEGA program (v. 6.0).Results. The prevalence of mutations associated with decreased susceptibility to elsulfavirine among HIV-infected treatment-naïve patients was 1.7% and 4.5% for the first and second groups of patients, respectively. All of the patients have only single resistance mutations which, according to the results of preclinical studies, cannot cause drug resistance. The use of elsulfavirine in real clinical practice among treatment-naïve patients has demonstrated good virological and immunological efficacy of the drug. As a result of 24 weeks of therapy in patients of the second group, no treatment ineffectiveness, and the development of drug resistance were observed. Among the patients of the third group, 6 patients (5.3%) have the virological failure of therapy associated with the resistance to the used drugs. All patients with virological failure had a resistance mutation profile associated with a high level of drug resistance to one of the drugs in the treatment regimen, lamivudine. Additionally, 1 patient had a combination of mutations that reduce susceptibility to elsulfavirine, and 4 patients had mutations that can reduce susceptibility to elsulfavirine in combination with other mutations.Conclusion. The low prevalence of mutations associated with a decrease in susceptibility to elsulfavirine and the absence of combinations of mutations make it possible to predict the successful use of this drug for Russian treatment-naïve patients. Reported cases of virological failure of antiretroviral therapy are difficult to interpret in the context of elsulfavirine due to the lack of an exact list of mutations and their combinations, and associations with the degree of resistance to it. This study describes for the first time the mutation profiles in patients with virological failure of therapy containing elsulfavirine and demonstrates the necessity of the further study of drug resistance profile to drug in vitro and in vivo.

Purpose Cystic fibrosis (CF) is one of the most common monogenic diseases with an autosomal recessive inheritance. Carrier screening leads to a reduction in the number of children born with CF disease. The aim of this study was to develop the custom panel for the diagnosis of heterozygous carriage of polymorphic variants in the CFTR gene and to establish their allelic frequencies (AF) in one of the Russian regions where ethnic Russians predominate. Patients and methods The diagnostic panel was designed on the basis of data from the register of CF patients in Russia for 2017 and validated on 22 blood samples of patients with previously genetically established CF. The study participants (n=642) for CF variants estimation were randomly selected from the population-based cohort study ESSE-Vologda. Genotypes were determined by real-time PCR on the QuantStudio 12K Flex Real-Time PCR System. Data processing was performed using the TaqMan Genotyper Software. Results The proposed diagnostic panel allowed simultaneous analysis of 60 variants of the CFTR gene. A total of 23 carriers of the following variants were identified among 642 participants: F508del (rs113993960) with a frequency of 2.02%, L138ins (rs397508686) and 394delTT (rs121908769) - 0.47%, CFTRdele2.3 (c.54-5940_273+10250del21080; p.S18Rfs*16) - 0.31%, R117H (rs78655421), and G542X (rs113993959) - 0.16%. The frequency of heterozygotes in the Russian population was 3.58% or 1:28 (CI95%: 2.28-5.33% by Clopper-Pearson exact method). Conclusion High frequency of heterozygous CFTR variants carriers and availability of highly productive diagnostic panel for detection of CFTR variants suggest the prospect of carrier screening for some common CF variants among Russian population.

The article describes a clinical case of monozygotic twins with hypertrophy of the organs of the lymphopharyngeal ring. The examination revealed IgG to the Epstein-Barr virus capsid antigen in both patients. One twin had Epstein-Barr virus DNA in the sample from the oropharynx. It was this child who had complaints typical of patients with adenoid vegetation, and he required surgical treatment (endoscopic shaver adenotomy and radio wave bilateral tonsillotomy). At the time of the initial examination and in the absence of complaints the second twin revealed no DNA of Epstein-Barr virus in the oropharynx. This patient was diagnosed with adenoids of 1-2 degree. Due to the complaints of the second twin that appeared during the following year of observation, with previously negative results on active Epstein-Barr virus markers served as the reason for a repeated specific laboratory examination. Epstein-Barr virus DNA was found in a sample from this child’s oropharynx. This case using the twin control method by partner enabled us to demonstrate the significance of Epstein-Barr virus in the pathogenesis and clinic manifestations of chronic diseases of the lympho-pharyngeal ring organs in children.

The HIV cascade model can be used as an epidemiological surveillance tool and for assessing the quality of medical care for HIV-positive people. It is possible to use the model for the entire population of people living with HIV, in various socio-demographic groups, by region, years and other indicators. This article describes the features of a HIV cascade model depending on the goals for its use.Каскадная модель медицинской помощи людям, живущим с ВИЧ, может быть использована в качестве инструмента эпидемиологического надзора и как один из компонентов оценки медицинской помощи ВИЧ-позитивным лицам. При необходимости и наличии данных возможно применение модели для всей популяции людей, живущих с ВИЧ, в различных социально-демографических группах или при оказании специальных видов помощи, по регионам, годам и другим показателям. В статье описаны особенности построения каскадной модели в зависимости от поставленных целей ее использования.

Anaplastic pancreatic carcinoma is a very rare histological subtype of pancreatic cancer, which is characterized by a more aggressive course than for conventional ductal adenocarcinoma. In this article, we consider the features of the clinical course, the difficulties of diagnosis in connection with the absence of pathognomonic signs of pancreatic cancer, and the morphological picture of this disease in a patient 60 years of age. This clinical case clearly demonstrates the complexities of the pancreatic carcinoma diagnosis, fast disease progression, and extremely unfavorable prognosis. It is important for clinicians to remember that this pathology often has a subclinical course, and the oncomarker levels are not always true.

To assess the safety and efficacy of autologous haematopoietic stem cell transplantation (auto-HSCT) in multiple myeloma (MM) patients with dialysis-dependent renal failure.During a period from May 2010 to December 2016 fourteen MM patients with dialysis-dependent renal failure aged 48 to 65 years underwent auto-HSCT. After the induction therapy complete response, very good partial response, partial response were documented in 64, 29, 7% of patients, respectively. In no case was a renal response achieved. Haematopoietic stem cell mobilization in most patients (13/14) was performed according to the scheme: G-CSF 10 g/kg. Melphalan in 3 dosages was used as pre-transplant conditioning: 100, 140 and 200 mg/m2; 13 patients underwent a single and in one case underwent a tandem auto-HSCT against the background of hemodialysis. Evaluation of the antitumor and renal response was assessed on the 100th day after auto-HSCT. Subsequently, against the background of programmed hemodialysis and in the setting of high-dosed melphalan (100200 mg/m2), 13 patients underwent a single and one patient underwent a tandem auto-HSCT. At +100 days after auto-HSCT, an antitumor response and renal response were assessed.The period of agranulocytosis after auto-HSCT was from 5 to 12 days (median 8,5) and was accompanied by infectious complications, cardiac and neurological dysfunctions. At +100 days after auto-HSCT, the complete response was confirmed in 71% patients and very good partial response was confirmed in 29% patients. The minimal renal response was registered in 2 patients (14%), hemodialysis was stopped. The transplant-related mortality was absent. After a median follow-up of 53 months 5-year progression-free survival was 59%, and overall survival was 93%.Carrying out auto-HSCT in patients with dialysis-dependent renal failure contributed to the achievement of a minimal renal response in 14% of cases, which allowed these patients to stop hemodialysis. Patients whose conditioning regimen was performed using melphalan at a dose of 200 mg/m2showed more frequent complications in the early post-transplant period compared to patients who received a lower dose of melphalan (100140 mg/m2). Auto-HSCT in MM patients with dialysis-dependent renal failure is a feasible and effective treatment method, which in some cases contributes to independence from hemodialysis.Цель.Оценить безопасность и эффективность трансплантации аутологичных стволовых клеток (ауто-ТГСК) крови больным множественной миеломой (ММ) с диализ-зависимой почечной недостаточностью (ПН). Материалы и методы.В ретроспективное исследование включены 14 больных ММ с диализ-зависимой ПН в возрасте от 48 до 65 лет, которым с мая 2010 по август 2018 г. выполнена ауто-ТГСК. После индукционного этапа лечения полная ремиссия, очень хорошая частичная ремиссия, частичная ремиссия документированы у 64, 29, 7% больных соответственно. Ни в одном случае почечный ответ не достигнут. Мобилизация стволовых кроветворных клеток у большинства больных (13/14) проводилась по схеме Г-КСФ 10 мкг/кг. В качестве предтрансплантационного кондиционирования использовался мелфалан в 3 дозировках: 100, 140 и 200 мг/м2; 13 больным выполнена однократная и в одном случае тандемная ауто-ТГСК на фоне программного гемодиализа. Оценка противоопухолевого и почечного ответа проводилась на 100-й день после ауто-ТГСК. Результаты.Период миелотоксического агранулоцитоза после ауто-ТГСК длился от 5 до 12 сут (медиана 8,5 дня) и сопровождался инфекционными эпизодами, кардиальной и неврологической дисфункциями. На +100-й день ауто-ТГСК полная ремиссия диагностирована в 71% случаев, очень хорошая частичная ремиссия у 29% больных. Почечный ответ зарегистрирован у 2 (14%) больных, программный гемодиализ им отменен и возобновления заместительной почечной терапии не потребовалось в течение 24100 мес после ауто-ТГСК. Летальность, связанная с трансплантацией, отсутствовала. При медиане наблюдения 53 мес 5-летняя выживаемость без прогрессии составила 59%, общая выживаемость 93%. Заключение.Проведение ауто-ТГСК больным с диализ-зависимой ПН способствовало достижению минимального почечного ответа в 14% случаев, что позволило прекратить выполнение гемодиализа этим пациентам. У больных, предтрансплантационное кондиционирование которым проведено с применением мелфалана в дозе 200 мг/м2, отмечены более частые осложнения в раннем посттрансплантационном периоде по сравнению с пациентами, получившими меньшую дозу мелфалана (100140 мг/м2). Ауто-ТГСК является эффективным методом лечения больных ММ с диализ-зависимой ПН, в ряде случаев способствующим достижению независимости от гемодиализа.

The article presents the results of the development of specialized 3D-GIS as a tool for structuring, storing, reproducing, processing and analyzing data for geotechnical monitoring of main pipeline facilities. The authors proposed a solution to the problem of the complexity of processing large amounts of data by creating a unified environment of geographically distributed information through a geo-portal and implementing services on the basis of the geo-portal for automated processing and analysis of information, as well as computational algorithms. The description of the structure and functionality of the developed 3D-GIS is given. Methods for obtaining and processing 3D data are disclosed, and the data is analyzed. Results of a quantitative assessment of changes in the natural environment, plan-elevation position and geometry of objects based on the data of several cycles of surveys by methods of ground and air laser scanning are presented. The advantages of 3D-GIS in solving problems of geotechnical monitoring, as well as the possibility of using 3D-models for solving other production and research problems are highlighted.

Subject. The article addresses tax incentives for capital investment in the framework of corporate income tax, and their effectiveness, estimated as the scale of application of incentive instruments. Objectives. We explore tax instruments intended to boost the investment activity of businesses in Russia, in the context of their demand by Russian organizations. Methods. To estimate the efficiency of tax incentives for boosting investment, we calculate absolute and relative values of reduction in the tax base, according to the data of the Ministry of Finance of the Russian Federation, the Federal Tax Service of Russia, and Rosstat, and the number of companies, using these tax instruments. Results. The set of tax incentives and preferences focused on stimulating the investment activity within the income tax is quite wide, however, their application imposes significant restrictions on taxpayers. The effectiveness of applied tax incentives remains rather low. A relatively modest number of organizations use early depreciation mechanisms for acquired fixed assets to reduce income tax. Bonus depreciation is more common, however, it is applied by a sufficiently low number of taxpayers, although to a significant proportion of newly entered items of property, plant and equipment. Accelerated depreciation, both the declining method of depreciation and increasing coefficients, are used less frequently than bonus depreciation. Conclusions. Prospects for expanding the investment activity of a business can be associated with investment tax deduction. Its effectiveness assessment is possible only in the medium term.

Subject. This article assesses the role of tax incentives for the Russian business' investment behavior. Objectives. The article aims to identify the relationship between the corporate income tax burden as an indicator responding to tax benefits application and the investment activities of Russian companies. Methods. For the study, we used the methods of analysis and synthesis, and the systems approach. The analysis covers the period from 2012 to 2018. The data of the Russian Federal State Statistics Service, Federal Tax Service of Russia, and the Ministry of Finance of the Russian Federation are the source of information for analysis. Results. The article summarizes the characteristics of the investment activity of the Russian business. However, the article does not reveal any obvious relationship between the income tax burden and the investment activity of the Russian business in the 2010s. There is also no link found between fixed investment and return on assets. Conclusions. The increase in income tax burden in the late 2010s, accompanied by a decrease in profitability, poses a threat to the active investment development of Russian organizations.

Russia’s economic growth is impossible without the extensive use of cloud and mobile technologies in the registration and accounting of taxpayers. The purpose of the study is to identify positive and negative aspects of introducing information and communication technologies into the registration and accounting tax procedures in various countries to develop recommendations for the improvement of these procedures in the Russian Federation. General and special theories of taxation constitute the methodological basis of the research. The method of the study is comparative analysis of two groups of countries: economically developed and catch-up countries. The authors assess the current situation with digitalisation in the states, systematize software used, and demonstrate that in economically developed countries digitalisation has a more pronounced effect on the quality of tax administration and economic growth. The research shows that progressive technologies applied by the Federal Tax Service of Russia for the registration and accounting of taxpayers influence the growth of tax revenues, primarily VAT. The most urgent tasks of reforming the modern taxpayer registration system include registration of property taxes, VAT on imports, income taxes, as well as development of digitalisation technologies for the registration and accounting procedures taking into account the trends in economic processes’ transformation towards a smart society. The widest possible introduction of digital registration and accounting of taxpayers is meant to significantly increase the efficiency of Russia’s tax system and contribute to the stable growth of the domestic economy.

The success and quality of large-scale epidemiological studies depends entirely on biomaterial quality. Therefore, when arranging the third Epidemiology of Cardiovascular Diseases and their Risk Factors in Regions of Russian Federation (ESSE-RF-3) study, increased attention was paid to specifics of collection, processing and further transportation of biological samples and related clinical and anthropometric data of participants from regional collection centers to Biobank.Aim. To develop a methodology for collection of high-quality biomaterials within the large-scale epidemiological study, involving the sampling, processing, freezing of blood and its derivatives (serum, plasma) in the regions, followed by transportation and storage of obtained biomaterial in the Biobank of National Medical Research Center for Therapy and Preventive Medicine (Moscow).Material and methods. To conduct the ESSE-RF-3 study, a design was developed, according to which the collection of venous blood samples in a total volume of 29,5 ml from each participant is planned in all participating regions in order to obtain and store samples of whole blood, serum and two types of plasma.Results. On the basis of international biobanking standards, ethical norms, experience from ESSE-RF and ESSE-RF-2, and literature data, a protocol for biobanking of blood and its derivatives was developed. The type and number of serum and plasma aliquots obtained, the required standard technical means and consumables, as well as logistic biomaterial requirements were determined. Training programs for regional participants were developed. By the beginning of August 2021, 180 thousand samples of whole blood, serum and plasma from more than 23 thousand participants from 28 Russian regions were collected, processed and stored.Conclusion. The presented work made it possible to assess and confirm the compliance of developed biobanking protocol with quality requirements. However, due to the coronavirus disease 2019 pandemic, by August 2021, the Biobank did not reach the maximum effectiveness predicted for the ESSE-RF-3 project.

L-asparaginase (L-ASNase) is a vital enzyme with a broad range of applications in medicine and food industry. Drawbacks of current commercial L-ASNases stimulate the search for better-producing sources of the enzyme, and extremophiles are especially attractive in this view. In this study, a novel L-asparaginase originating from the hyperthermophilic archaeon Thermococcus sibiricus (TsA) was expressed in Escherichia coli, purified and characterized. The enzyme is optimally active at 90 °C and pH 9.0 with a specific activity of 2164 U/mg towards L-asparagine. Kinetic parameters KM and Vmax for the enzyme are 2.8 mM and 1200 µM/min, respectively. TsA is stable in urea solutions 0–6 M and displays no significant changes of the activity in the presence of metal ions Ni2+, Cu2+, Mg2+, Zn2+ and Ca2+ and EDTA added in concentrations 1 and 10 mmol/L except for Fe3+. The enzyme retains 86% of its initial activity after 20 min incubation at 90 °C, which should be enough to reduce acrylamide formation in foods processed at elevated temperatures. TsA displays strong cytotoxic activity toward cancer cell lines K562, A549 and Sk-Br-3, while normal human fibroblasts WI-38 are almost unsensitive to it. The enzyme seems to be a promising candidate for further investigation and biotechnology application.

The aim of the study was to test whether P-αB can be positioned as a preventing and treating agent for cardiovascular diseases.Materials and methods. The study was performed on sexually mature male Wistar rats. Endothelial dysfunction was modulated by a 7-days intraperitoneal administration of L-NAME at the dose of 2.5 mg/100 g. P-αB, or erythropoietin (EPO), was used for therapy at the dose of 2.5 µg/100 g × 3 times for 7 days, the total dose was 7.5 µg/100 g. The function of endothelium was estimated by an endothelium-dependent and endothelium-independent vasodilation. In addition, a histological assessment of the abdominal aortic wall state and the analysis of eNos, Tnf and Il-1β genes expression were performed. To estimate prothrombotic properties, P-αB and EPO were administered, at the doses of 2.5 and 5 µg/100 g (3 times a day for 7 days, the total doses were 7.5 µg/100 g and 15 µg/100 g, respectively) and on the 8th day, the time of ferric (III) chloride-induced carotid artery thrombosis was estimated.Results. Theresults of the functional tests for endothelium-dependent and endothelium-independent vasodilatation, as well as the histological picture of the aorta have evidenced that P-αB and EPO do not affect L-NAME-induced hypertension but improve the endothelium function. At the same time, P-αB shows a significantly higher endothelial-protective activity, reducing the coefficient of endothelial dysfunction from 5.1±0.15 to 2.72±0.12. In addition, P-αB has significantly increased the expression of eNos and reduced the expression level of Tnf and Il-1β mRNA genes. Carrying out Ferric (III) chloride-induced carotid artery thrombosis has revealed that P-αB (5 µg/100 g × 3 times a day for 7 days, total dose was 15 µg/100 g) has a lower but statistically significant prothrombotic activity than EPO.Conclusion. P-αB can be positioned as an atheroprotector because of its ability to prevent the death of endothelial cells, as well as to reduce remodeling and proinflammatory activation of the vascular wall. However, the prothrombotic properties of P-αB limit its use as a preventing and treating agent for atherosclerosis-associated diseases.

Rare condition characterized by an intensive and excessive breast enlargement is known as gigantomastia. Gestational gigantomastia manifests during pregnancy and could represent a life-threatening condition for both the mother and the fetus, therefore the risk of spontaneous abortion complicates the choice of treatment approach. We present a clinical case of a patient requesting medical assistance with a progressive breast growth. The onset occurred on the 5th week of gestation and, subsequently, was aggravated by distal tissue necrosis. The ambiguity of treatment approach in such situation is based on, on the one hand, the insecurity of watch-and-wait approach due to the high risk of septic complications and, on the other hand, the increasing danger of fetal loss in the case of surgical treatment during the first trimester of pregnancy. After an adequate assessment of mothers health state, a decision was made towards the wait-and-see tactic until the complete formation of the placental barrier. A total bilateral mastectomy was performed at the 19th week of pregnancy, with a favorable outcome for the patient and her child. This case emphasizes the significance of an individual, interdisciplinary approach to the choice of management for patients with this pathology.

Определены требования и ключевые принципы реализации комплексной транспортно-логистической услуги на железнодорожном транспорте. Выделены ключевые перспективные направления научной работы, связанные с оказанием таких услуг. Определены этапы реализации комплексных транспортно-логистических услуг. Практическое значение статьи заключается в разработке необходимых условий и прикладных технологических инструментов для реализации комплексных транспортно-логистических услуг на российских железных дорогах.