Monoclonal antibodies (mAbs) are the most promising and most intensively replenished type of bioactive pharmaceuticals. Currently, there are over 100 different mAbs approved by the FDA and other regulating agencies for treatment of oncological, infectious, systemic, autoimmune and other diseases. Design of antibodies neutralizing pathogens of socially significant infections, such as HIV, hepatitis viruses, SARS-CoV-2, is a separate direction. The SARS-CoV-2 pandemic has shown how urgent it is to have a technological platform enabling production of fully human antibodies. The development of recombinant DNA technology and antibody phage display enabled compilation of libraries of antigen-binding fragments and screening with target antigens. This review discusses the advantages and disadvantages of phage display, including use of single-domain antibody technology based on the heavy chain variable domain. We describe the state-of-the-art (and practical results of its application) technology enabling production of human antibodies by sorting and sequencing the genome of individual memory B cells, using monoclonal virus-neutralizing antibodies against SARS-CoV-2 as an example. The prospects of further development of the recombinant human antibody production technology are discussed; in particular, we consider creation of sequences of variable fragments of antibodies with the help of artificial intelligence.

This review looks at analytical capabilities and composition of portable equipment based on lateral flow immunoassay for rapid indication of human pathogenic bacteria, viruses and toxins which was developed by the State Research Institute of Biological Instrumentation under the auspices of the Federal Medical and Biological Agency of Russia. The review presents technical characteristics and composition of portable test kits UIHE-1 designed for taking monoanalytical and multi-analytical lateral flow immunoassay on pathogenic microorganisms and toxins in washes from environmental objects surfaces and in culture media; it also describes kits EkB and EkB-01 for analysis of biological aerosol samplers contents. Information is given on the analytical properties of luminescence lateral flow immunoassay kit ULI-1, an on the experimental prototype of fluorimeter-reflectometer "Zondazh". The technical characteristics of indication kits were compared with those of foreign origin, areas for improvement of portable equipment based on lateral flow immunoassay were indicated.

Frequent resulting disability and case mortality support the urgency of investigation of the immune response mechanisms triggered by severe injury (SI) in children. This study aimed to determine the informative immunological criteria of traumatic injury severity and prognosis in children (n = 43) based on the assessment of expression of CD39 and CD73 ectonucleotidase in populations of regulatory T cells (T_reg, CD4⁺CD127^lowCD25^high) and T-helper 17 cells (Th17, CD4⁺CD161⁺CD3⁺) in SI cases grouped by the outcome (favorable (SIfav, n = 24), unfavorable (SIunfav, n = 17) and lethal (n = 2)). With the help of flow cytometry, we identified a pronounced decrease in the absolute number of Treg and Th17, as well as T_reg and Th17 expressing CD39 and CD73, in the early post-traumatic period. In the SIfav and SIunfav groups the relative number of Treg and Th17 cells expressing CD39 differed significantly (p <0.05); it was substantially higher form the first to the third day post injury in the SIunfav group. The level of T_reg CD39 (44.4%) is a premise for an unfavorable outcome in children surviving an SI. In fatality cases, we registered extremely low ectonucleotidase expression rates: CD39⁺Tr_eg — 9.52% (9.52–13.75) and CD39⁺Th17 — 0.92% (0.74–1.1). In the SIunfav group, the intensity of fluorescence (FL) of CD39 on T_reg cells in the early post-traumatic period was higher than seen in the SIfav group. The threshold value for the average fluorescence intensity (FL) of CD39 on Treg was 8.25 c.u. In fatality cases, the T_reg CD39 FL values were extremely low: 3.95 c.u. (3.7–4.67). The results of the study indicate that in children, the expression of CD39 and CD73 in T_reg and Th17 populations is significantly associated with the severity of injury and outcome of the traumatic disease.

One of the approaches to cartilage tissue restoration problem relies on cellular technologies that use iPSCs, induced pluripotency stem cells that are an unlimited source of cellular material for tissue engineering with significant differentiation potential. However, there are no standardized protocols for chondrogenic differentiation of iPSCs. This study aimed to make cartilage tissue samples using 3D spheroid cultures and following four chondrogenic differentiation protocols, then compare characteristics of the cartilage samples made under different protocols and isolate the most effective way of differentiation. The iPSCs were differentiated chondrogenically, the four protocols were "long", "short", "combined" and with conditioned medium from a primary culture of autologous chondrocytes; the combinations of TGFβ1, BMP2, Chir 99021, and PK factors varied. Microwell plates were used to make spheroids. Immunocytochemical staining, real-time PCR and histological staining enabled assessment of the synthesis and expression profiles. High rates of synthesis and expression of chondrogenic markers Sox9, aggrecan, type II collagen were observed in spheroids experimented with under the "long", "combined" protocols and the conditioned medium protocol. The "combined" differentiation protocol made chondrogenesis most effective, and conditioned medium was highly efficient in inducing and supporting chondrogenic differentiation.

Lactoferrin, artemisinin, and azithromycin exhibit a broad spectrum of antiviral, immunomodulatory, and anti-inflammatory effects. The experiments show that these drugs partially inhibit the infection caused by SARS-CoV-2 in vitro. This allows us to conclude that the effects on the entry of virions into cells mediated by each of these substances taken separately are insufficient for complete inhibition of the SARS-CoV-2 infection. The study was aimed to perform in vitro assessment of cytotoxicity and antiviral activity against the laboratory SARS-CoV-2 strain of the mixture of active ingredients: lactoferrin, artemisinin, and azithromycin. We used the Vero CCL81 (ATСС) cell line and the Dubrovka laboratory strain of SARS-CoV-2 (GenBank ID: MW161041.1), isolated in the Vero CCL81 cell culture from the nasopharyngeal swab of patient with СOVID-19. Cytotoxic effects and antiviral activity against SARS-CoV-2 of the drug mixture were assessed based on the cytopathic effects using the MTT (methylthiazolyldiphenyl-tetrazolium bromide) assay. Hydroxychloroquine was used as a reference drug. It has been shown that at high (MOI 100) and low (MOI 20) multiplicity of infection used in the Vero CCL 81 cell culture, the mixture of artemisinin, lactoferrin and azithromycin has a significant effect on the SARS-CoV-2 reproduction, and IC50 (half maximal inhibitory concentration) is estimated as the 1 : 2 dilution in both cases. The findings make it possible to conclude that the studied mixture is low toxic and shows significant antiviral effects in vitro.

Bacterial infections caused by antibiotic resistant strains of Klebsiella pneumoniae are among the most dangerous threats for the world's public healthcare. Treatment with bacteriophages and/or their derivatives could become one of the alternative methods for therapy of infections caused by K. pneumoniae. The study was aimed to isolate from the environment and characterize the capsule-specific K. pneumoniae bacteriophages that are useful for therapy and possess the polysaccharide depolymerase genes. Bacteriophages were isolated from the river water samples by enrichment method. The host range of bacteriophages were assessed using the collection of 180 K. pneumoniae clinical strains. Bacteriophage whole genome sequencing was performed on the MiSeq platform (Illumina). Four new bacteriophages from different taxonomic groups were isolated and characterized during the study: vB_KpnM_NDO71 (Vequintavirinae family), vB_KpnS_MAG26fr (Casjensviridae family), vB_KpnS_MDA2066 (Ackermannviridae family), and vB_KpnS_PMM-G3 (Drexlerviridae family). Bacteriophages vB_KpnM_NDO71, vB_KpnS_MAG26fr, and vB_KpnS_PMM-G3 had a narrow lytic spectrum and lysed all strains with the capsular type of the host: KL45, KL19 or KL28, respectively. Bacteriophage vB_KpnS_MDA2066 showed lytic activity against strains with two different capsular types: KL19 and KL107. Bacteriophages were strictly virulent and contained no integrase genes, potentially dangerous toxin genes or antibiotic resistance determinants. This allows them to be used in therapeutic practice. Receptor-binding proteins represented by polysaccharide depolymerases were predicted for each bacteriophage.

The process of production of inactivated influenza vaccines involves a stage of inactivation of both the influenza virus and the possible viral contaminants that can come from the raw materials (chicken embryos). One of such contaminants is the avian leucosis virus. The minimum viral contaminant load reduction that the inactivating agents should guarantee is by 4 lg/ml; this or higher level of the deactivating ability ensures the finished vaccine is free from viral contaminants. The purpose of this work was to cultivate the leucosis virus to the titer of 5 lg/ml (minimum) and to measure the reduction of the avianleucosis virus titer in influenza vaccine intermediates upon exposure to the inactivating agents. The RAV-1 and RAV-2 leucosis virus strains and influenza vaccine intermediates such as virus[1]containing allantoic fluid and virus concentrates were used in the study. Avian leucosis virus titers were determined by enzyme immunoassay. We created conditions for cultivation of the RAV-1 and RAV-2 avian leucosis virus strains in the primary culture of chicken embryo fibroblasts (CEF); the inactivating agents considered were the most commonly used β-propiolactone and UV radiation. It was found that after 12 hours of exposure to β-propiolactone, the RAV-1 avian leucosis virus load decreased by 4.61 ± 0.46 lg, and that of RAV-2 strain — by 4.33 ± 0.33 lg, which indicates that β-propiolactone is an effective inactivating agent. Five minutes of exposure to UV radiation reduces the RAV-1 strain viral load by 4.22 ± 0.31 lg and RAV-2 strain viral load by 4.44 ± 0.48 lg.

This study aimed to develop a method allowing to improve safety of use of robotic medical rehabilitation devices by designing and testing an algorithm for calculation of the angular positions of rehabilitation robotic manipulators or robotic prostheses and allowing to reproduce the natural arc of a human arm under control of a CVS. The Introduction section supports the urgency of development of the methods granting control over positioning of robotic manipulators with the help of a computer vision system (CVS) and thus guarantee safety of patients and medical personnel in the context of work with medical robotic rehabilitation devices. The Materials and Methods section contains a brief description of the robotic arm used in this study, a description of the existing approaches to calculation of angular positions of drives, and a description of the proposed algorithm. The final sections compare application of the proposed algorithm and existing methods of calculation of angular positions of drives of robotic manipulators (robotic prostheses) and outline the possible directions for further improvement.

Active (red) bone marrow (AM) exposure due to ingested bone-seeking radionuclides can lead to grave medical consequences. For example, a radioactive contamination of the Techa River in the 1950s caused exposure to AM for riverside residents and led to chronic radioactive exposure syndrome in some of them, with higher risk of leukemia. The main sources of the marrow exposure were the bone-seeking beta emitters ^89,90Sr. Improving the dosimetry of AM internal exposure is an important step in clarifying the risks of chronic radiation exposure for riverside residents. To evaluate the energy absorbed by AM from incorporated ⁹⁰Sr it is customary to use computational phantoms where radiation transport can be emulated. A phantom is a representative digital representation of skeletal bone geometry and AM The goal of this work was to develop a computational phantom of a newborn skeleton for dosimetry of AM from incorporated ⁹⁰Sr. The researchers have used the Stochastic Parametric Skeletal Dosimetry method (SPSD), where hematopoietic sites were modeled as a set of phantoms of simple geometric shape describing individual skeletal bone areas. The AM content in the skeleton as well as the phantom parameters were evaluated on the basis of published measurements of real bones. As a result, a computational phantom of the main skeletal hematopoietic sites was generated for a newborn baby, including 34 phantoms of bone areas. The simulated phantom simulates the bone structure as well as the variability of skeletal parameters within the population and corresponds well to measurements of real bones.

Personnel safety is a priority when decommissioning obsolete nuclear facilities. The study was aimed to develop the methodological basis for the medical and sanitary support of the nuclear industry enterprise personnel radiation safety during the nuclear legacy elimination on the example of Siberian Chemical Plant (SCP, Seversk). The study involved the data of the SCP employees' medical and dosimetric register containing information about all cases of death (with an indication of the cause) of former and current employees of the enterprise. The study results were used to justify selection of the area for development of scientific and methodological support of activities in the field of medical and sanitary support of radiation safety during the nuclear legacy elimination. Death rates and the risk of dying from cancer of certain localizations (trachea, bronchi, lung, skin, stomach, colon, lymphoid, hematopoietic and related tissues, breast and prostate glands) in the nuclear industry enterprise employees were assessed. The directions for improving the medical support of the nuclear enterprise employees and the population of the surveillance zones during the nuclear legacy elimination were defined. The findings will make it possible to adjust the medical support of the nuclear industry enterprise employees in order to extend their working longevity, as well as to reduce the adverse radiation-induced health effects in people engaged in the nuclear legacy elimination.

Mortality rate is one of the main indicators of how healthy a population is, and planning and implementing measures aimed at reducing morbidity and increasing life expectancy in the population is impossible without an adequate analysis and interpretation of mortality data. At the same time, as pointed out by many researchers, there are factors external to a human body being that can have a significant effect on the mortality rate in a population. This study aimed to assess the impact of one of these factors, the number of beds in hospitals (per 10,000 people) of cities with population exceeding 100,000 people. The analysis included data from Rosstat (Russian statistics service) on the population size, mortality, number of hospital beds, average monthly wages in 12 cities within the period from 2017 through 2019. Five cities from these 12 were selected as a more homogeneous subgroup in terms of socio-economic conditions. We found a positive correlation between mortality rate per 1000 inhabitants (R > 0.7; p < 0.009) and the number of hospital beds per 10,000 people in the sample of 12 cities. This correlation was higher (R ≥ 0.9; p < 0.037) in the more homogeneous subgroup. A factor that may condition this correlation may be that of deaths of people from other regions in hospitals of the cities in question, which are counted when estimating the mortality rate and have a significant effect on that estimation. The results of the study point to the need to differentiate between people registered in a city and those living there permanently when assessing mortality rate therein.

Medical care at the pre-hospital stage requires concentration of attention from ambulance workers and induces stress on the functional systems of their bodies. The spread of COVID-19 has increased the workload on mobile ambulance teams and worsened functional state of the team members' central nervous systems. This study aimed to investigate the impact of professional activity on changes in the indicators reflecting attention capacity, allocation and switching in mobile ambulance healthcare workers in the context of the COVID-19 pandemic. We used the Number Square method to assess these indicators. The participants were divided into groups with the help of standard tens, through standardization of the number of digital symbols, correct answers, mistakes made and time spent. The clear signs of fatigue by the end of the work shift are the decreased attention capacity, registered in 40.48% (p < 0.0001) of participants, and deteriorating attention allocation, registered in 64.29% (p < 0.05). The dynamics of the indicators were revealed to be associated (negative trends) with length of service and age. The registered values did not decrease at each subsequent shift, which proves the rest period between the shifts ensures a sufficient recovery. Decreased attention capacity and allocation by the end of the shift, as objective signs of fatigue, depend on age and length of service. Lack of negative dynamics shift-to-shift shows that the functional resources of the body are restored during the prescribed rest period even in the intense conditions of mobile ambulance teams' work during the COVID-19 pandemic.

The rapid switch on of the transient short-term responses involved in adjustment of homeostasis plays a key role in human adaptation to low temperatures that is essential for adjustment to low-temperature environment. The network of signaling pathways together with metabolic regulators provide sufficient plasticity of the cells of immune system, the normal function of which is extremely important for successful human adaptation. Sufficient energy supply to immunocompetent cells makes it possible to form an adequate immune response to any negative factor and to ensure adaptive functional rearrangements. The study was aimed to assess the variants of the immunocompetent cell metabolic pathways involved in acquiring individual cold sensitivity. A total of 180 people aged 25–55 (130 females, 50 males) were assessed before and after the short-term whole body cooling. Enzyme immunoassay was used to define the levels of IL10, IL6, TNFα, irisin, transferrin, sTfR, HIF-1α, Sirt3 in peripheral blood and cell lysate. The levels of glycogen (cytochemical methods) and ATP (luciferin-luciferase assay) in lymphocytes were defined. The decrease in peripheral blood lymphocyte levels after cooling was indicative of the formation of immediate adaptive response and activation of glycolysis amid less intense inflammatory response. The increase in the levels of circulating lymphocytes after the cold esposure was associated with activation of inflammatory responses. The lower ratio of HIF-1α/SIRT3 metabolic regulators was found in the surveyed volunteers who showed no changes in the levels of lymphocytes. This indicated predominance of mitochondrial activity in adaptation to low temperatures.

There are single and multi parameter bioclimatic indices that enable assessment of the impact of weather and climatic conditions on health of a human being. This study aimed to comparatively assess health risks in the Arctic's open area using the bioclimatic indices. Relying on the data from the Central Siberian Department for Hydrometeorology and Environmental Monitoring (Krasnoyarsk) that describe the weather on Cape Chelyuskin in 2010–2022, we assessed the temperature, the integral indicator of body cooling conditions (IIBCC), the wind chill factor (WCF), the effective (ET) and the net effective temperature (NET), and the universal thermal climate index (UTCI). It was found that the WCF temperature can characterize the degree of frost risk as established by the IIBCC: the indicator has the critical frost risk period lasting November through April, and the respective risk level by WCF is "discomfort" (coolness) and "very cold", that by UTCI — "extreme stress", by ET — "caution — frostbite of exposed skin" (shorter), by NET — "threat of frostbite" (longer). The IIBCC and the UTCI show that the risk of cold injury in the conditions of Cape Chelyuskin is year-round: according to the IIBCC, its level changes between moderate (4–6 months) and critical (4–6 months), and according to UTCI, it may be very strong (4 months), and very strong and extreme (8 months). We have proven the advantages of UTCI over other integral indicators in assessment of the cold-related health risk and updated the basis for the hygienic requirements regulating practice of work in the open or in unheated enclosed spaces during the cold season.

The anti-doping efforts on the part of medics should be constantly improved, which means the exploration and analysis of ways to increase the effectiveness of such efforts should be constant. SWOT analysis (Strengths, Weaknesses, Opportunities, Threats) is one of such ways. It investigates internal problems and resources of an organization and the influence of external factors. This study aimed to improve the anti-doping efforts based on the analysis of their strengths and weaknesses, taking into account external threats and directions of development. We have conducted an express SWOT analysis of anti-doping work in medical organizations of the Federal Medical Biological Agency of Russia and compiled a simple matrix. The factors under consideration are internal, which can be controlled, and external, which are often uncontrollable but should be accounted for. We identified the most significant factors influencing organization of this line of work, compiled the SWOT matrix that allows assessing the possible resources for intensifying the anti-doping work, determined its strengths and weaknesses, threats and opportunities imposed by the environment in this activity takes place in. The express SWOT analysis enabled evaluation of the factors that have the greatest impact on the organization of anti-doping work. Informational and educational programs, including workshops for medics and monitoring of their level of knowledge, can be the key line of activity in the context of such efforts.

The relevance of this study is due to the need to answer the question of how the factors of digital medium affect the development of mental functions in the younder generation. The study was aimed to assess the effects of the social media interference factor on memory (auditory-speech and visual-figurative) consolidation in adolescents. The sample was 130 adolescents aged 11–17. The groups were formed based on the age stages (11–12, 13–14, 15–17 years). The study involved the use of the method for the diagnosis of the short-term auditory-speech and visual-figurative memory span. Viewing video content and reading the fragment of the fiction book were used as interference. A significant decrease in the short-term auditory-speech and visual-figurative memory span was observed in adolescents. The short-term memory span is reduced in the context of social media interference (prolonged continuous viewing the heterogenous visual-acoustic and visual-speech content). The high risk of the long-term memory loss due to the impact of the social media interference factor on memory consolidation in adolescents is empirically proven. The more the duration of the maximum continuous video stream and the total time the adolescents spend on Internet (including social media), the larger is the loss of information.