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The review examines the role of domestic space medicine and physiology in space exploration and emphasizes that domestic space medicine will focus on biological, physiological, and psychological aspects of humans. The main task of specialists in the field of space medicine and physiology is to prepare for future stages of manned astronautics, using existing accumulated experience, new developments, and assessing the forecast of probable events and situations that the human will inevitably encounter in this new world. [ABSTRACT FROM AUTHOR]

The review examines molecular and cell changes in the pathogenesis of endometriosis. Literature data on innate and adaptative immunity are presented, the role of changes in the hormonal status and nuclear receptors for steroid hormones is considered, and a possible epithelial–mesenchymal transition in endometrial cells and at the site of their attachment during the formation of an ectopic focus of endometrium is discussed. The role of the combined action of various factors in the pathogenesis of endometriosis is discussed. [ABSTRACT FROM AUTHOR]

Ionizing space radiation safety for the crew is one of the goals of biomedical support of lunar missions. The results of dose estimations at the International Space Station and experimental data analysis, as well as the modeling of anticipated doses beyond Earth's magnetosphere, advocate for the acceptability of ~1.5-month missions provided that the existing dose limits are not exceeded. [ABSTRACT FROM AUTHOR]

The system of medical care used in the Russian segment of the International Space Station in space missions is directed to support space crews in orbital flights. The system gives the priority to the telemedicine rather than medical procedures performed by the crew autonomously. The long-term experience showed effectiveness of the existing system for medical support of orbital flights; however, travels beyond the low-Earth's orbit add substantial limitations calling for reconsideration of approaches to the crew medical care. Among the special features of these missions will be increasing time of autonomy. There is a high probability that crews will have to make medical decisions by themselves and computer-assisted systems are likely to be a proper tool of health care. The software of medical inventory control and practice guidance developed in the Institute for Biomedical Problems (IBMP) enhances quality of the day-to-day use of medical resources at the Russian Orbital Segment and can serve as a prototype of a medical decision support system within the intelligent circuit aboard future piloted spacecraft. [ABSTRACT FROM AUTHOR]

Abstract: The paper presents an automated integrated analytical method developed for the assessment of medical information at a large industrial company organized into divisions and operating in different climatogeographic and ecological conditions, including unfriendly environments. The use of automatic means for data acquisition, aggregation, and analysis allows us to expand a set of indicators and increase the efficiency of decision making on optimization of processes and resource provision aiming to attain strategic goals of a medical provision system. We have developed a methodology for the organization and analysis of integrated indicators in a multilevel hierarchy, in which we proposed to use synthetic indicators characterizing different aspects of this medical provision system at each level of abstraction. The software package allows us to calculate and visualize integrated indicators characterizing employees' health state and evaluate the quality of the medical provision system, whereas the use of geoinformation technologies makes it possible to represent the data with a spatial reference and solve logistics optimization tasks. [ABSTRACT FROM AUTHOR]

The paper is dedicated to analysis of artificial neuron network efficiency in processing the data of remote medical monitoring of participants in the Sirius-17 analog study conducted by the Institute of Biomedical Problems in 2017. The authors propose an ingenious data processing algorithm involving a self-learning multilayer artificial neuron network (ANN) capable of predicting health dynamics with the help of an integrated index of subjective health assessment. [ABSTRACT FROM AUTHOR]

Tolerance of the chest-to-back accelerations (+Gx) at the peak value of 6.7 g was evaluated in two Soyuz crew members during the ballistic landing after an off-nominal launch. The G-tolerance of crew member 1 (CM1) when passing through the dense layers of the atmosphere was assessed as good based on analysis of reported subjective sensations and results of objective physiological investigations: the physiological reactions of the body to the action of g-force were of a moderate nature; no critical signs limiting G-tolerance were noted. The G-tolerance of crew member 2 (CM2) was assessed based on analysis of objective physiological information only, which allowed us to consider it good. CM1 highly appreciated the experience gained during flight preparation, including the experience of centrifuge (CF) spins, which enabled him to act professionally in an emergency situation. The tolerance of g-force with a maximum value of 6.7 units by the ISS crew after the off-nominal Soyuz launch was assessed as good. [ABSTRACT FROM AUTHOR]

Abstract—Spore-forming bacteria have a unique resistance to negative environmental conditions, including aggressive space factors, and are an excellent model for studying adaptation mechanisms and survival strategies at the molecular level. The study analyzed the genome of Bacillus velezensis, which remained viable after a 2-year exposure in outer space on the outer surface of the ISS as part of the Test space experiment. A comparative analysis of the draft genomes of the exhibit strain and the ground control did not reveal significant changes; the average nucleotide identity was 99.98%, which indicates the ability of microorganisms to maintain genome stability in space conditions, due to both increased stress resistance of bacterial spores and efficient operation of the system of repair of accumulated changes. The study of a single nucleotide polymorphism in the genome of B. velezensis revealed nine point substitutions, three of which are in intergenic regions, six in protein-coding genes, three of them are missense mutations, two nucleotide deletions leading to a shift in the reading frame, and one synonymous substitution. The profiles of the housekeeping genes were determined during MLST typing and it was found that the allelic profiles obtained for B. velezensis T15.2 and 924 strains do not correspond to any of the previously described sequence types.The presented results indicate the ability of B. velezensis bacteria to maintain the viability of spores and the integrity of the genome for a long time under extreme conditions of outer space, which is important for the problem of planetary protection, as well as the potential possibility of performing biotechnological processes based on B. velezensis during space exploration. [ABSTRACT FROM AUTHOR]

Chromatography–mass spectrometry analysis of samples recovered from dried blood spots obtained during a year-long stay at the Vostok Antarctic station within the 65th Russian Antarctic Expedition identified 6798 peptides with the maximum level of confidence, from which it became possible to identify 1239 different proteins. The names of proteins whose concentration changed by the 4th and 12th months of stay at the station were determined, and common proteins typical for periods of research were identified. Both period-specific and common reliable changes in the concentration of blood proteins that formed by the 4th and 12th month of stay at the station were determined by bioinformatics methods. Signaling pathways and methods of adaptation of the body when exposed to extreme conditions are discussed based on proteomics data. The data obtained suggest that the implementation of professional activities under conditions of prolonged hypobaric hypoxia, isolation, and hypokinesia at the Vostok station in Antarctica is accompanied by changes in the blood proteome, affecting primarily the processes of maintaining chemical-energy homeostasis at the molecular, cellular, tissue, organ, and systemic levels. [ABSTRACT FROM AUTHOR]

The mechanoelectrical feedback in the heart is based on the work of mechanically gated (MGCs) and mechanosensitive (MSCs) channels. Since microgravity alters the heart's morphological and physiological properties, we hypothesized that the expression of both MGCs and MSCs would be affected. We employed RNA transcriptome sequencing to investigate changes in the gene transcript levels of MGCs and MSCs in isolated rat ventricular cardiomyocytes under control conditions and in a simulated microgravity environment. For the first time, our findings demonstrated that simulated microgravity induces alterations in the gene transcript levels of specific MGCs, such as TRPM7, TRPV2, TRPP1, TRPP2, Piezo1, TMEM63A, TMEM36B, and known MSCs, including K2P2.1, K2P3.1, Kir6.1, Kir6.2, NaV1.5, CaV1.2, KV7.1. However, other voltage-gated channels and channels lacking a voltage sensor remained unaffected. These findings suggest that the altered expression of MGCs and MSCs could lead to changes in the net currents across the membrane, ultimately impacting the heart's function. [ABSTRACT FROM AUTHOR]

The research is a complex experiment that had a double-blind randomized placebo-controlled study. An effective measurement of the parameters of the human body was examined on eight apparently healthy subjects during an exposure of 8 h in altered magnetic conditions. The results of the experiment did not reveal significant risks for the functional state of the human body with a decrease in the multiplicity of about 1000 times. [ABSTRACT FROM AUTHOR]

Hypomagnetic conditions (HMCs) will be an integral part of the complex of factors affecting astronauts in long-term interplanetary missions outside Earth's magnetic field. The adaptation of the human body under these conditions will affect the regulatory processes in various physiological systems, the molecular pathways of which, with the participation of proteins, have not yet been studied. In order to fill this gap, dry blood spots collected on a special paper from healthy volunteers were studied by proteomic methods in two sessions of a model experiment: with HMCs and in a placebo session. The experiment was carried out by the method of double-blind control, with the participation of the same volunteers in both sessions. 1219 different proteins were semiquantitatively determined in the samples. In the HMC series, changes relative to individual values before the experiment series were detected in three proteins: tropomyosin alpha-3 chain (TPM3), abhydrolase domain-containing protein 14B (ABHD14B), and acetylcholinesterase-associated protein (CUTA). However, comparison of the data obtained in the placebo session smoothed out the effect of HMCs on changes in the above proteins. The results may mean either the absence of HMC influence with a short exposure and the absence of a cumulative effect, or they are unreliable due to the insufficient number of subjects in the sample. [ABSTRACT FROM AUTHOR]

This article summarizes the experience of managing patients with COVID-19-associated pneumonia treated in one of the intensive care units of a multidisciplinary hospital with and without a heated oxygen–helium mixture. It has been shown that the use of a heated oxygen–helium mixture in the complex therapy of pneumonia caused by SARS-CoV-2 is effective. A comparative analysis of the clinical manifestations of the disease and the results of laboratory tests in the main and control groups of patients confirm with a high degree of reliability the improvement of blood oxygenation, the normalization of the acid–base balance and the positive dynamics of the main parameters, which ultimately increases the efficacy and reduces the time of treatment. [ABSTRACT FROM AUTHOR]

Complex interactions between circuits regulating blood circulation are determined by multidirectional effects of a variety of factors in a system maintaining homeostasis at an optimal level. An important methodological approach used in the study opens up new opportunities for analyzing the patterns in intersystem interactions of regulatory circuits and processes that are nonlinear and are in a stable non-equilibrium state. An experiment with 5-day dry immersion (DI) was carried out to determine the degree of synchronization and the timing of involvement in adaptation process for regulatory circuits of the circulatory system. The circuits were evaluated by analyzing the heart rate variability (HRV) (nervous regulatory circuit), blood chemistry (humoral regulatory circuit), and the urinary proteomic profile (metabolic regulatory circuit). DI is commonly used in gravitational physiology to study the effect of microgravity on physiological systems of the body. The study involved 11 healthy male volunteers aged 28 ± 4 years. A principal component analysis was used to study the regulatory interactions at all DI stages. The functionality of each circuit was analyzed as a whole, which made it possible to reveal hidden patterns that remain undetectable when individual variables are analyzed. The direction and time of response were estimated for various circuits of the regulation of blood circulation to characterize their reactivity, which reflects the adaptive capabilities of the body. Concerted estimates were obtained for different regulatory circuits. [ABSTRACT FROM AUTHOR]

The paper describes the main stages of the protocol and results of a unique 21-day experiment undertaken at the Russian Federation State Research Center Institute of Biomedical Problems of the Russian Academy of Sciences (RAS) (IBMP) under the conditions of Dry Immersion. A cohort of participants consisted of 10 healthy male volunteers (the mean age 29.3 ± 3.56 years). The experiment has demonstrated the feasibility and safety of conducting long-duration immersion exposures, confirming the results obtained during previous shorter exposures, as well as allowed us to describe the dynamics of events during extended chronic stays in the conditions of simulated hypogravity. The accumulated experiences are useful for further research into the efficiency of applying the conditions of simulated microgravity and other prophylactic means as countermeasures against negative effects occurring to human body during extended support and weight unloading. [ABSTRACT FROM AUTHOR]

Oxidative damage to main cell components (DNA, lipids, and proteins) in the human body during a spaceflight (SF) is more intense than in normal conditions because of the imbalance between production and elimination of free radicals and reactive oxygen species. Proteomics methods were used to estimate the frequency of oxidative posttranslational modifications (PTMs) in blood plasma proteins from Russian participants in semi-annual flights to the ISS. The influence of oxidative PTMs detectable after a SF on functional features was considered for the protein groups that are involved in metabolism of the extracellular matrix (ECM), lipid metabolism, immune functions, and control of inflammation according to a bioinformatics analysis. The protein components of apolipoproteins (APOA1, APOA2, APOA4, APOL1, and APOE) showed excessive oxidation in post-flight samples as compared with their pre-flight state, suggesting distortion of their vasculoprotective properties. A twofold or greater increase in the intensity of oxidative modification was observed for chains of both membrane and secretory immunoglobulins (Igs). The composition of oxidized fragments in chains (κ, γ1, γ2, γ4, and µ) of constant Ig domains indicated that the effector or signaling functions of Igs might be altered. Structural components of the ECM and ECM-associated compounds found in the extracellular fluid are a complex molecular hub that links immune functions, vascular competencies, inflammation control, protease–antiprotease balance, and hemostasis. The components of this system were considered in their close relationship. [ABSTRACT FROM AUTHOR]

The prospects of interplanetary missions make it relevant to develop standard tests to find criteria for the correction of preventive measures in a long space flight in order to ensure a peak in physical performance by the time the interplanetary activity is completed. Currently, tests are being developed to assess physical performance. One of them can be the currently developed locomotor test with a stepwise increasing load in the active mode of movement of the treadmill. It is of interest to assess the effect of this load on changes in the profile of proteins associated with the cardiovascular system from the standpoint of the possibility of using them as markers of its response to physical activity. In article analyzes the results of an experimental study of the proteome of human urine after a dosed step-increasing load and discusses the possible role of the identified proteins that can be attributed to the functioning of the cardiovascular system. The study involved practically healthy volunteers aged 18.6 ± 0.7 years, weighing 75.7 ± 8 kg (n = 12). The urine proteome was evaluated by chromatography-mass spectrometry and analyzed by bioinformatics methods. For the first time, data on the proteomic response to a locomotor test with a stepwise increasing load in the active mode of web movement in a group homogeneous in autonomic status are presented. As a result of the analysis, 429 proteins were identified, 69 of which significantly changed. Based on bioinformatics analysis, processes related to the work of the heart, vascular tone, and vascular permeability were identified. Ten proteins are described that are associated with the processes of the quick response of the cardiovascular system to dosed physical activity. The obtained results will help in choosing standard criteria for assessing the physiological cost of physical activity. [ABSTRACT FROM AUTHOR]

The balance of production and elimination of free radicals and reactive oxygen species is disturbed in the human body during a space flight. Oxidative stress is a common pathogenetic link in the violation of the functions and structure of various body tissues. The main cellular components, such as DNA, lipids, and proteins, undergo oxidative damage. In this study, proteomic methods were used to analyze the frequency of detection of oxidative post-translational modifications of blood plasma proteins obtained from Russian participants in International Space Station (ISS) flights. The effect of the oxidative modification detected after space flight on the functional features of protein groups that regulate the hemostasis and complement activation cascade is examined. According to published data, the increase in oxidative post-translational modifications of proteins in the hemostasis system affects not only the protein structure but also the fibrin formation, as well as its viscoelastic and biochemical properties. Oxygenation of proteins with oxidation-sensitive methionine residues, including apolipoprotein A-I, thrombomodulin, and von Willebrand factor, increases the risk of developing vascular diseases and thrombosis. Oxidized phospholipids are deposited in the vessel wall, potentiating atherosclerotic changes. It was shown that the oxidative modification of the key protein, clusterin, changed the regulation of the complement cascade, as well as the association of the immune system with the coagulation cascade. [ABSTRACT FROM AUTHOR]

A rationale for the concept and strategy of monitoring of the atmospheric chemical composition and water quality are provided for manned spacecraft to be used for long-term and interplanetary flights. The main risk factors are formulated for a change in atmospheric and water composition during interplanetary space flights. A promising version of the analytical system for operational control of air and water quality in manned spacecraft is described considering these risk factors. Several gas analysis methods are proposed to be used in this system to partially overlap the nomenclature of detected species with respect to particularly important (critical) species. The water quality in the system is monitored by two instruments: one for measuring the total carbon content and the other for analyzing the ionic composition of water. [ABSTRACT FROM AUTHOR]

This paper provides a review of experiments with extended confinement and isolation of small groups of volunteers in controlled environments. These studies provide opportunities to test approaches and tools enhancing the systems of biomedical support to space crews and to lay the groundwork of remote autonomous space missions in future. This review describes scenarios, goals, objectives, and main results of the long-duration isolation projects carried out at the Ground-Based Test Facility of the Institute for Biomedical Problems (IBMP) since 1960s and a forthcoming series of the Sirius analog studies. The authors elaborate on the fundamental principles of successful and productive accomplishment of this type of projects. [ABSTRACT FROM AUTHOR]

Abstract: Cell immunity indices were studied in 6 female participants in the Moon-2015 project at the age of 25 to 34 years. Peripheral blood was analyzed for lymphocyte subtypes CD3+, CD3+CD4+, CD3+CD8+, CD19+, and CD3-CD16+CD56+ and monocytes and granulocytes that express signal recognition receptors of the Toll-like (TLR) family (TLR2, TLR4, TLR6) localized on the surface of cells. The results of the study have demonstrated a distinct effect of short-term isolation on the immune system ability to mobilize. Rotation on a short-arm centrifuge (SAC) together with a nine-day isolation in a chamber caused diverse responses of the adaptive and innate immune systems. Apparently, the changes observed reflect a complex adaptation process in the innate and acquired immunity at the early stage of adaptation to isolation and also to the exposure to +Gz accelerations (head-to-pelvis) during rotations on SAC. [ABSTRACT FROM AUTHOR]

Abstract: Cell components of the adaptive and innate immunity were investigated in essentially healthy volunteers aged 27 to 34 years. Peripheral blood was analyzed for absolute and relative counts of lymphocyte phenotypes CD3+, CD3+CD4+, CD3+CD8+, CD19+, CD3-CD16+CD56+, CD3+CD16+CD56+, CD3+CD25+, CD45RA+, CD4+CD45RA+, and monocytes and granulocytes expressing pattern recognition receptors of the Toll-like family (TLR2, TLR4, TLR6) on the cellular membrane. A single cold exposure at -70°С was found to affect cell factors of the human immune system dramatically. Very low temperatures produce different changes in adaptive and congenital components of immunity representing a complex process triggered by the stress-reaction to a short stay in air cryosauna. [ABSTRACT FROM AUTHOR]