Preview

Extreme Medicine

Advanced search
Online First

RADIOBIOLOGY

196
Abstract

Introduction. The use of nuclear energy may give rise to emergency situations accompanied by the release of radioactive elements into the environment, potentially leading to radiation injuries to personnel of such enterprises or the entire population. In this context, the development of effective and safe approaches for protecting the body from radiation injuries remains highly relevant [1].

Objective. Study of the radioprotective properties of purified turpentine oil (PTO) and its combination with sunflower oil.

Materials and methods. At the first stage of research, the composition of PTO was determined and an optimal solvent was selected. The administration route (subcutaneous, intraperitoneal, intramuscular) of turpentine-oil solutions (at doses of 1806 mg/kg, 1290 mg/kg, 774 mg/kg, 516 mg/kg, and 2580 mg/kg) in 360 mice of both sexes (weighing 18–20 g) was established. At the second stage, the radioprotective efficacy of turpentine–oil solutions was evaluated in 50 white mice (70%, 50%, 30%, 20% turpentine-oil solutions were administered intramuscularly at doses of 1806 mg/kg, 1290 mg/kg, 774 mg/kg, 516 mg/kg 24 h before and after irradiation at a dose of 8.0 Gy (LD100/30)). At the third stage, the optimal dose ensuring the greatest radioprotective efficacy was determined in 120 white mice of both sexes (irradiation at a dose of 7.7 Gy (LD100/30); intramuscular administration of a 70% turpentine–oil solution at doses of 1806 mg/kg, 180.6 mg/kg, 90.3 mg/kg, 45.15 mg/kg, 22.57 mg/kg 72 h before and after irradiation). At the fourth stage, the radioprotective efficacy of 50% and 70% turpentine–oil solutions was evaluated in 36 outbred white rats of both sexes (irradiation at a dose of 9.3 Gy; after 3 days, a single subcutaneous administration of PTO at a dose of 258 mg/kg, anti-radiation serum at a dose of 50 mg/kg; intramuscular administration of a 70% turpentine–oil solution at a dose of 90.3 mg/kg, a 50% solution at a dose of 64.5 mg/kg). The content of malondialdehyde in the blood serum was determined on days 3, 5, 7, and 14 after irradiation. At the fifth stage, the optimal timing for the administration of the 70% turpentine–oil solution was determined in 80 white mice irradiated at a dose of 8.0 Gy. Statistical data analysis was performed using the GraphPadPrism v. 8.0 software package.

Results. Highly purified, high-oleic refined sunflower oil was identified as the optimal solvent for PTO. The preferred route of administration is intramuscular for turpentine–oil solutions and subcutaneous for PTO. The most pronounced radioprotective activity was observed for 70% and 50% turpentine–oil solutions administered as a single intramuscular injection 24 h before and after irradiation. To ensure 80% survival of lethally irradiated animals with a single prophylactic use and 60% survival with therapeutic use, intramuscular administration of the developed agent at doses of 90.3–180.6 mg/kg is required during the first 12 days before or during the first 4 days after lethal irradiation. The application of turpentine–oil solutions in various concentrations modified the course of the pathological process: by day 5 after treatment initiation, lethally irradiated animals showed a decrease in lipid peroxidation intensity.

Conclusions. A radioprotective agent has been developed that exerts both prophylactic and therapeutic effects by inhibiting lipid peroxidation products induced by ionizing radiation. The formulation is characterized by a a simple preparation technology, an effective route of administration, and an optimized ratio of components that ensures good absorption. As a result, a single intramuscular injection of the developed formulation can serve as an alternative to prolonged oral administration of terpenoid-based biologically active compounds.

134
Abstract

Introduction. The study of the effects of preconceptive (before conception) and in utero radiation exposure, including the risk of malignant neoplasms (MNs) in the offspring of individuals exposed to occupational radiation, is a complex and ambiguous problem in radiation epidemiology.

Objective. Epidemiological analysis of carcinogenic effects among offspring whose parents were exposed to occupational preconceptive radiation and radiation during pregnancy at the Mayak Production Association.

Materials and methods. A retrospective analysis of outcomes in the form of oncopathology was conducted among 35,500 individuals, of whom 14,593 were offspring of workers at the Mayak Production Association (PA) — the first nuclear industry enterprise in Russia, operating since 1948. The comparison group included 20,872 individuals whose parents were not exposed to radiation at work and were not resettlers from radioactively contaminated territories. The study samples were drawn from individuals born in 1948–1988 in the closed administrative-territorial unit (CATU) of Ozersk, located near the nuclear facility. The follow-up period was 72 years (1949–2020). The data sources for the epidemiological analysis of cancer incidence among offspring whose parents were Mayak PA workers include: the Mayak PA personnel medical and dosimetric registry, the Children’s Registry (includes the population exposed in childhood to technogenic impact due to Mayak PA activities), the Child Population Health Registry, the Cancer Registry, and the Cause of Death Registry of the CATU Ozersk population. Information on accumulated absorbed doses of external gamma radiation was extracted from the “Dosimetry System of Mayak PA Workers — 2013.” Statistical analysis was performed using nonparametric statistics methods: frequency comparison was conducted using the χ² test (Pearson’s chi-squared test).

Results. A comparative analysis of the structure and frequency of primary MNs showed that the incidence spectrum differs by sex across all study groups. Among male offspring, the main contribution came from MNs of the digestive tract; among female offspring — from MNs of the breast and female genital organs. A comparative analysis of “crude” cancer incidence rates showed a statistically significant excess of incidence rates in offspring of exposed mothers compared to similar rates in the offspring of exposed fathers. A significant excess of MN incidence rates was observed in offspring of exposed parents compared to the control group, both overall and for specific MN localizations. The highest proportion of MNs was observed in groups of Mayak PA workers with “zero” accumulated doses of external gamma radiation, both among offspring of exposed fathers and mothers and among individuals exposed in utero, which requires further detailed analysis.

Conclusions. The cohort of offspring of Mayak PA workers can be considered an important source of data for the epidemiological study of carcinogenic effects. Given the relatively young age of the cohort of Mayak PA offspring (47 years on average for offspring of exposed fathers, 51 years for offspring of exposed mothers, and 41 years for the control group), further epidemiological monitoring is necessary.

108
Abstract

Introduction. The electron paramagnetic resonance (EPR) method, based on determining the concentration of free radicals generated in materials surrounding a person under the influence of ionizing radiation, allows for reliable estimates of absorbed doses in individuals exposed to uncontrolled irradiation. However, materials intended for use as objects in EPR dosimetry must meet fairly stringent requirements, including availability, detection limit, temporal stability of the EPR signal, and sufficient radiation sensitivity. Therefore, although ionizing radiation induces free radical formation in virtually all materials, not all of them can be used to obtain information about absorbed radiation doses.

Objective. Selection of optimal materials for assessing absorbed doses of ionizing radiation in victims of accidental exposures using the EPR method.

Materials and methods. A standard Bruker Elexsys E580 X-band spectrometer with a SuperHighQ cylindrical resonator was used to record EPR spectra. A UELR-10-10S2 linear electron accelerator was used for sample irradiation. The study examined samples of biological materials (hair, fingernails), as well as materials commonly associated with humans in everyday life, such as plastic, cotton fabrics, fabric from disposable medical masks, and smartphone glass.

Results. The results showed that each of the studied materials has its own advantages and disadvantages for EPR dosimetry. The radiation sensitivity of hair samples was inversely proportional to their melanin content: the higher the pigment concentration (and, consequently, the darker the hair), the lower the radiation sensitivity and the higher the background melanin signal. To account for the intrinsic melanin signal, an additional measurement is recommended — recording the hair color via a photograph taken under a microscope. Fingernail samples, which, like hair, are keratinous formations but lack melanin, represent an alternative. A drawback of biological materials such as hair and fingernails is their relatively low sensitivity, with a lower limit of detection (LOD) exceeding 10 Gy. High radiation sensitivity was demonstrated by uncolored cotton fabric samples (LOD = 1 Gy). The material of protective masks exhibited several times higher radiation sensitivity. Stable EPR signals were obtained from transparent plastic buttons. Smartphone glass proved to be the most radiation-sensitive material, with a LOD not exceeding 0.5 Gy; however, the variation in sensitivity among such glasses was significant, even among smartphones of the same model. The variability in radiation sensitivity of the investigated samples ranged 20–50%.

Conclusions. When selecting materials for estimating absorbed doses using the EPR method, the following witness materials for radiological events are preferred: smartphone screen glass, uncolored cotton clothing fabrics, materials from protective masks, and transparent plastic. When using hair as a biological dosimeter, the measurement procedure is characterized by increased complexity, and the results may contain a systematic overestimation of the estimated doses, particularly in the case of dark-colored hair. Fingernail samples, in turn, exhibit poor stability of the radiation-induced signal, which is difficult to distinguish from background signals of non-radiation origin. The variability in the sensitivity of the studied sample materials indicates the need for individual calibration using additional irradiation.

44
Abstract

Introduction. The cognitive effects of intermediate-frequency electromagnetic fields (300 Hz — 10 MHz) from household and industrial sources have been insufficiently explored, with existing data remaining contradictory and primarily limited to young animals. Given the rapid aging of the global population, experimental assessment of how alternating magnetic fields affect cognitive function in an aged organism is of particular importance.

Objective. To assess the effects of a pulsed magnetic field on cognitive function and motor activity in physiologically aged mice.

Materials and methods. Cognitive function and motor activity were assessed using the Morris water maze (MWM) and open field behavioral test. Eighteen-month-old outbred CFW mice of both sexes were exposed to a pulsed magnetic field (PMF; 28 kHz, 140 ± 15 µT per pulse) for 5 min daily over 5 consecutive days prior to the start of behavioral tests and subsequently for 5 min daily before MWM testing. Control animals were subjected to sham exposure following the same schedule.

Results. PMF-exposed mice exhibited enhanced learning ability compared to the control group. On day 5 of testing, the escape latency and path length to the hidden platform were significantly reduced by 30% compared to the control group, while the success rate of finding the platform increased by 75%. On day 6 of MWM testing, the probe trial revealed that PMF-exposed mice crossed the former platform location three times more frequently than controls. In the open field test, no statistically significant effect of PMF exposure on motor activity was observed.

Conclusions. A pulsed magnetic field with a pulse repetition frequency of 28 kHz and an induction of 140 ± 15 µT reduces the natural decline in cognitive function. While further research is needed to clarify how the observed effects depend on PMF parameters (frequency, modulation, and exposure intensity), our findings suggest that PMF could potentially be used to address age-related cognitive changes in humans.

SPORTS MEDICINE

191
Abstract

Introduction. Neurofeedback is a type of biofeedback that targets brain rhythms. The prospects for its application in rehabilitation and sports medicine stem from its non-invasive and non-pharmacological nature of changing the functional state through controlled parameters and body functions. At present, alpha-rhythm neurofeedback training is widely used in sports medicine, whereas the effects of beta-rhythm neurofeedback remain largely unexplored.

Objective. The study aims to investigate the effect of beta-rhythm neurofeedback training on the functional state of body systems in male athletes during intensive training camps conducted in the mid-mountains.

Materials and methods. The study involved 47 highly qualified male athletes divided into a main group of 27 individuals (median age: 21 [18; 24] years) and a control group of 20 individuals (median age: 20 [18.5; 22.5] years). A neurofeedback session targeting beta rhythms consisted of a graphic session (10 min) and a game session (16 min); the course comprised 8–10 sessions. Along with psychophysiological testing, the physiological parameters of the cardiovascular, respiratory, and nervous systems were recorded before the first and after the last sessions. Statistical data processing was performed using Statistica 13.0 software.

Results. A comparison of the parameters of bodily functions in male athletes before and after the neurofeedback training course showed a decrease in physiological strain, as evidenced by heart rate variability, hemodynamics, respiratory parameters, and galvanic skin response. Also, the indicators of mental performance and beta rhythms were noted to increase relative to the control.

Conclusions. The course of neurofeedback training targeting beta rhythms was found to have a positive effect in male athletes, which manifested itself in improved function of the central and autonomic nervous systems, increased cardiac efficiency, and optimization of the respiratory cycle. The obtained results open up prospects for athletes to achieve higher performance by reducing physiological strain and, consequently, fatigue during intensive activities.

174
Abstract

Introduction. Concussion, whose diagnosis is primarily based on clinical evaluation, is a pressing issue in modern sports. To improve diagnostic methods for concussion in high-performance sports, the Sport Concussion Assessment Tool (SCAT) protocol is used. However, as the original versions of this protocol are published in English, their application in other languages presents challenges in terms of cultural adaptation and linguistic nuances.

Objective. To evaluate the comparability and equivalence of the three proposed Russian-language 10-word lists for memory assessment in athletes within the SCAT-5 protocol.

Materials and methods. An examination of 446 athletes was conducted using the SCAT-5 protocol (373 males, 73 females; median age 37 [26; 43] years). Only athletes who showed no abnormalities during baseline (pre-competition) testing were included. The Russian-language version of the SCAT-5 protocol, featuring three different word lists for memory assessment, was prepared and adapted by specialists from the National Center of Sports Medicine of the Federal Medical and Biological Agency. Depending on the word list used to assess immediate memory, the athletes were divided into three groups. Evaluation metrics included the total number of symptoms, symptom severity score, immediate memory, and delayed recall. Statistical analysis was performed using IBM SPSS Statistics 23.0 software.

Results. Comparison of the integrated immediate memory scores across groups revealed no statistically significant differences (p > 0.05). Similarly, analysis of the integrated delayed recall scores showed no significant intergroup variations (p > 0.05). A positive correlation was found between the integrated immediate memory and delayed recall scores in each group (Group 1: r = 0.629, p < 0.001; Group 2: r = 0.663, p < 0.001; Group 3: r = 0.591, p < 0.001). No correlations were observed between immediate memory and the total number of symptoms (r = –0.011, p = 0.824) or symptom severity (r = –0.015, p = 0.747).

Conclusions. Each of the three proposed word lists demonstrated methodological validity comparable to the original English-language versions of SCAT protocols. These lists are interchangeable and are validated for use in the Russian-language versions of the SCAT-5, SCAT-6, and subsequent protocols where memory is assessed using 10-word sets. The implementation of this protocol enables more objective diagnosis and monitoring of athletes throughout various stages of post-concussion recovery.

203
Abstract

Introduction. Traumatic brain injury (TBI) is a pressing issue in high-performance sports. Although most sports-related TBIs are classified as mild, their frequent occurrence and resulting cumulative effect can negatively impact an athlete’s health. Furthermore, this impact may not become apparent until several years after the injury, and sometimes only after the athlete has retired from the sport.

Objective. To identify the most frequent clinical manifestations associated with the long-term effects of traumatic brain injury in active and retired athletes from various sports.

Materials and methods. In order to assess the prevalence of symptoms associated with various TBI consequences, a total of 902 active and former athletes from Russian national teams were surveyed anonymously using a secure online platform, LimeSurvey, with a proprietary domain. The participants included 662 (73.4%) adult and 240 (26.6%) minor athletes. The study methodology was based on a questionnaire and did not include objective instrumental examinations. The questionnaire presented to the athletes contained questions clarifying anamnestic data and the presence of symptoms that could serve as clinical manifestations of the long-term effects of intracranial injuries. The entire sample of athletes was divided into groups according to age at the time of the survey (adults and minors). The group of adult athletes was also subdivided based on the number of TBIs in their history, the presence of contact/impacts during training (contact and non-contact sports), and age (18–30 years; 31–40 years; 41–50 years; ≥ 51 years). Statistical data analysis was performed using IBM SPSS Statistics 23.0 software.

Results. The prevalence of concussion among the adult athletes was statistically significantly higher than among the minors (15.3% vs. 2.5%, p < 0.001). The most common issues reported by the adult athletes with a history of concussion were sleep (36.6%) and visual disturbances (23.8%), as well as cognitive (25.7%), behavioral (22.8%), and affective (27.7%) disturbances. The aforementioned abnormalities were statistically significantly more frequent in the athletes participating in contact sports (p < 0.05). The athletes aged 18–30 years most commonly noted affective disturbances and changes in sleep, while visual disturbances were more prevalent in older age groups.

Conclusions. The most common clinical manifestations of TBI consequences in athletes consist of a complex of affective, cognitive, and behavioral disturbances, as well as impaired sleep and vision. Most consequences of intracranial injuries present with non-specific symptoms. Therefore, a crucial approach to optimizing the biomedical support system for athletes with a history of TBI consists in continuous monitoring of their health status post-injury. This involves developing screening protocols, followed by the formation of risk groups and early identification of impairments, which will help prevent or slow their progression.

115
Abstract

Introduction. The relevance of the study is substantiated by the ongoing state policy, the increasing number of children and adolescents engaged in physical education and sports, the high rate of injuries sustained during sports activities, and, consequently, the need to implement innovative treatment methods that minimize the duration of therapy and ensure the fastest possible return to the training process. Assessment of the subjects’ quality of life during research is one of the indicators (components) of the comprehensive evaluation of the effectiveness of the implemented medical technologies.

Objective. To assess the quality of life of underage athletes (aged 10–17 years inclusive) from Russian national teams with injuries and damage to major joints after a course of platelet-rich plasma therapy (PRP).

Materials and methods. Single-center, prospective, controlled, open-label study involving 22 adolescent athletes: median age 16 [15.25; 17.0] years (girls — 17 [16.0; 17.0] years; boys — 16 [14.5; 16.0] years) with injuries and lesions of large joints. PRP therapy (three injections at one-week intervals) was performed according to a standardized closed protocol used in the medical institution, using a commercial Arthrex kit. The following were performed: objective examination, consultations with an orthopedic traumatologist, pain assessment using a visual analog scale, muscle strength assessment according to the six-grade Hislop and Montgomery classification, functional tests to assess the integrity of the anterior cruciate ligament — the Lachman test and the ligaments of the knee and ankle joints — the anterior drawer test, clinical and laboratory tests (complete blood count), instrumental examinations (MRI — magnetic resonance imaging). Quality of life of adolescent athletes was assessed using the PedsQL 4.0 questionnaire. Statistical data processing was performed using Excel and the JASP v.0.16 software package.

Results. After the cycle of PRP therapy, athletes demonstrated a statistically significant improvement in quality-of-life scores as assessed by the PedsQL 4.0. The greatest positive dynamics, an increase of 23.1% (73 [63; 87] points at initial examination vs. 83 [81; 94] points at follow-up assessment), was observed on the role functioning scale. Physical functioning scores improved by 13.7% compared to baseline, while emotional functioning showed moderate improvement (6.7%). Statistically significant positive dynamics (p < 0.001) before and after PRP therapy were identified for eight items across four scales, with the most pronounced changes reported by respondents on the physical and role functioning scales. A statistically significant positive dynamic in pain intensity was also recorded after PRP therapy, with the maximum effect observed after two injections. The reduction in pain intensity was not associated with improvement in quality-of-life scores; however, this aspect may be related to the specific stage of physiological maturation and requires further study of the influence of individual factors on quality-of-life assessment by adolescent athletes.

Conclusions. PRP therapy minimizes pain and also has a positive impact on the quality of life of juvenile athletes with musculoskeletal injuries, manifesting not only in improved physical condition but also in emotional, role, and social functioning. Quality of life assessment may serve as an additional criterion for evaluating the PRP therapy effectiveness for major joint injuries in juvenile athletes.

112
Abstract

Introduction. In recent years, due to the increase in cardiovascular diseases and mortality among young patients, increasing attention has been paid to lipid metabolism disorders in children. Despite the proven cardioprotective effect of regular physical activity, lipid metabolism disorders are detected in a significant proportion of professional athletes (20–35.8%). Key risk factors include: dietary patterns, intake of dietary supplements and certain medications, excessive training loads, and insufficient recovery. To date, there are no standardized reference values for lipid profile parameters adapted to the age, gender characteristics, and specificity of sports activity in adolescent athletes. Furthermore, the task of developing criteria for cardiovascular risk stratification in the pediatric population remains unresolved, leading to late diagnosis of pathological conditions and untimely initiation of preventive and therapeutic interventions.

Objective. To determine the directions for the prevention of lipid metabolism disorders in adolescent athletes.

Discussion. Based on the results of the conducted literature analysis, it was revealed that the most prognostically unfavorable factors are non-modifiable factors: familial hypercholesterolemia and elevated lipoprotein(a) levels. Among modifiable factors, the key role is played by nutritional disorders (excess saturated fats and carbohydrates in strength sports, chronic energy deficiency in aesthetic sports), the specific characteristics of the sport, as well as the uncontrolled use of sports supplements and pharmacological agents, particularly anabolic steroids. Hyperhomocysteinemia deserves special attention, as its prevalence among athletes is higher than in the general population.

Conclusions. Dyslipidemias in adolescent athletes are predominantly secondary in nature, which requires a comprehensive assessment taking into account genetic predisposition, dietary patterns, type of sport, and pharmacological history. The feasibility of including extended lipid screening in the in-depth medical examination program for young athletes has been substantiated.

175
Abstract

Introduction. Physical exercise is one of the most powerful environmental factors modulating epigenetic modifications of the genome. The regulation of gene activity via the chemical modification of DNA, histone alterations, and non-coding RNAs serves as a link between training and the developing athletic phenotype. However, published data remain fragmented and often contradictory due to methodological challenges, heterogeneous cohorts, and a lack of protocol standardization.

Objective. Systematization and synthesis of current data on the influence of physical exercise on epigenetic modifications of the genome, analysis of their contribution to the processes of adaptation, recovery, and formation of the risk of pathological conditions in athletes, as well as assessment of the prospects for the use of epigenetic markers in sports medicine.

Discussion. Physical exercise induces specific changes in the three main components of the epigenome. Acute and chronic loads cause hypomethylation of the promoters of energy metabolism genes (PPARGC1A, PDK4, PPARD), which is accompanied by increased expression and mitochondrial biogenesis. Histone modifications (acetylation, phosphorylation of H3.3-Ser-31, lactylation) alter chromatin packing density. The spectrum of microRNAs depends on the type and duration of training; however, information on individual microRNAs (including miR-1) remains contradictory, largely due to differences in methodology (participant training status, time points, normalization method, sex). Signaling cascades (AMPK, MAPK, IGF-1/Akt, NF-κB, NFE2L2) integrate energetic signals and the epigenetic response. The epigenetic response is tissue-specific and is modulated by sex, age, and ethnicity. Promising directions include the analysis of exerkines, including microRNAs from extracellular vesicles, and nutricepigenetics.

Conclusions. Physical exercise consistently induces characteristic epigenetic modifications that participate in adaptation and can be considered as potential biomarkers of an athlete’s functional state. Promising areas of application in sports medicine include monitoring recovery through epigenetic clocks, predicting injury and overtraining, personalizing training, and extending the Athlete Biological Passport with epigenetic markers. Implementation of the results into clinical practice requires overcoming methodological limitations and further prospective research.

97
Abstract

Introduction. Within the framework of the State Programme “Development of Physical Culture and Sport”, adaptive physical education and Paralympic sport are actively developing. Under these conditions, developing model characteristics of functional fitness for Paralympic athletes with musculoskeletal impairments (MI) becomes particularly important. The aim is to improve the effectiveness of the training process both at the stage of athletic advancement and during athlete selection.

Objective. Determination of model characteristics of functional performance in Paralympic winter sport athletes with MI for the implementation of sports training during the Olympic cycle up to 2030.

Materials and methods. A retrospective analysis was conducted on 1037 testing protocols for physical performance parameters of 176 Paralympic athletes (2015–2025) competing in winter sports: cross‑country skiing, “sitting” category (LW 5/7–12) and “standing” category (LW 2–5/7); sledge hockey, “sitting” category (LW 5/7–12); alpine skiing, “standing” category (LW 2–5/7); wheelchair curling (LW 5/7–12). Functional metrics were determined via an incremental exercise stress test protocol established by the Federal Science Center of Physical Culture and Sport for able-bodied athletes, which was modified for upper‑body work using a hand ergometer. For standing cross‑country skiers, an incremental test to volitional exhaustion was performed by means of an HP Cosmos treadmill: 3-minute stages with workloads starting at 100 W for both men and women and increasing progressively by 50 W per stage (treadmill incline: 1°). Conversely, sitting athletes underwent an incremental test using a hand ergometer: 3-minute stages with workloads increasing by 20 W starting at 40 W for men and at 20 W for women. The same hand ergometer protocol (3-minute stages; 40 W starting workload, 20 W increments) was applied to Para ice hockey players. For Para alpine skiers and snowboarders, an incremental test to volitional exhaustion was conducted using a Schiller bicycle ergometer (Switzerland): 3-minute stages, with workloads increasing progressively by 35 W starting at 100 W for men and at 75 W for women. Gas exchange variables were measured throughout the test using an Oxycon Pro breath-by-breath gas analyzer. Electrocardiography was monitored continuously using a CARDIOVIT CS‑200 system during the exercise protocol, as well as during a 10-minute recovery period. The efficiency of energy supply mechanisms for muscle activity was evaluated based on these physical performance metrics. Statistical analysis was performed using Statistica software, version 23.0 (StatSoft Inc., USA).

Results. The developed reference profiles for physically impaired athletes can be applied at all stages of long‑term athlete development. Specifically, during the foundational stages of training, low (below the 3rd percentile) and below‑average (3rd–10th percentiles) values can be interpreted as average and above average for that developmental cohort. Conversely, at the advanced training stage, average and above‑average percentile ranks can be classified as high performance indicators. This shift reflects the progressive training demands, the enhancement of functional capacity, and the transition to elite levels of athletic performance.

Conclusions. The identified model characteristics for key parameters of functional fitness during exercise testing can be used in the scientific‑methodological and biomedical support of Paralympic athletes in winter sports. The obtained results complement the database of scientific research aimed at improving the training system for Paralympians with MI in winter sports and enhancing their athletic achievements.

8
Abstract

Introduction. Given the continuously increasing complexity of modern sports, rising training intensity, and growing demands at competitions, studying the mechanisms of swimmers’ adaptation to extreme physical loads has become particularly relevant. The obtained data may serve as a scientific basis for optimizing training programs and individualizing load distribution.

Objective. To characterize adaptive responses to maximal-intensity exercise in swimmers across different qualification levels.

Materials and methods. Adaptive changes in the autonomic nervous, cardiovascular, and respiratory systems were studied in swimmers performing high-intensity swimming over a 500-m freestyle distance. The experiment involved 81 participants, who were divided into three groups of 27 individuals each, according to their professional level: low, moderate, and high. To assess the cardiovascular system, systolic and diastolic blood pressure and heart rate (HR) were measured in the subjects before and after completing the trial. HR was recorded using a portable cardiac monitor placed on the left upper arm and on the index finger of the right hand. To evaluate the pulmonary circulation, the exhaled nitric oxide (NO) level was measured with a NOBreath V2 nitric oxide analyzer. The following parameters were calculated: pulse pressure, mean arterial pressure, stroke volume, cardiac output, total peripheral vascular resistance, Quaas index, Kerdo index, Robinson index, and adaptive capacity.

Results. The results demonstrated a direct relationship between the time to complete the 500-m freestyle swimming trial and the athletes’ professional level: group 1 – 792 ± 25.2 s, group 2 – 655 ± 30.2 s, and group 3 – 468 ± 24.6 s. In swimmers with a high professional level, the following post-exercise changes were observed: a 90.8% increase in cardiac output (p < 0.05), driven by a 41.9% rise in stroke volume (p < 0.05) and a moderate 33.5% HR elevation (p < 0.05); a 47.2% reduction in total peripheral resistance (p < 0.05); and an 11.2% increase in NO levels (p < 0.05). Correlation analysis revealed an association between swimming trial performance and adaptive capacity, HR, and the Robinson index. In swimmers with low and moderate professional levels, the changes reflected an exhaustive response pattern. A pronounced HR increase was observed with a relatively modest rise in stroke volume. Exhaled NO levels decreased by 10.1% (p < 0.05) in the low-level group and by 3.7% (< 0.05) in the moderate-level group. The increases in cardiac output were substantially lower – 49.1% (< 0.05) and 75.4% (p < 0.05), respectively – than those observed in the high-level swimmers.

Conclusions. With increasing professional level, athletes develop a complex of adaptive changes that enable them to cope more effectively with high loads during intense swimming. In swimmers with low and moderate professional levels, the response to exercise was exhaustive in nature: a pronounced HR increase was observed alongside a negligible rise in stroke volume and a decrease in NO levels. In contrast, swimmers with a high professional level demonstrated a n economical adaptive response: a balanced increase in cardiac output was achieved through elevated stroke volume and a moderate rise in HR; additionally, exhaled NO levels increased and autonomic regulation was optimized. Collectively, these adaptations support greater efficiency in overcoming high-intensity loads when swimming a 500-m distance.

8
Abstract

Introduction. Professional sports are associated with significant physical and psychological loads, which can impair athletes’ health, increase anxiety, negatively affect sleep, and ultimately lead to a decline in their quality of life. This may be particularly pronounced in children and adolescents during periods of active growth and pubertal changes. Assessments covering quality of life and other psychoemotional parameters in adolescent athletes are an important diagnostic direction, allowing comprehensive analysis of the health status of young athletes and adjustment of the effectiveness of therapeutic and diagnostic measures.

Objective. To assess the quality of life, levels of trait and state anxiety, and sleep quality in adolescent athletes of the national teams of the Russian Federation.

Materials and methods. A cross-sectional single-center study was conducted, involving 203 young athletes (40 males (19.7%) and 163 females (80.3%) aged 13–18 years (mean age 15.0 [13.0; 17.0] years), who were members of the national teams of the Russian Federation in 13 sports (volleyball, freestyle wrestling, Muay Thai, synchronized swimming, softball, sports acrobatics, artistic gymnastics, dance sports, taekwondo, wushu, figure skating, field hockey, rhythmic gymnastics). Assessment of quality of life in the children of the study groups was performed using the Russian version of the Pediatrics Quality of Life Inventory (PedsQL™ 4.0); self-assessment of anxiety levels was performed using the Spielberger–Hanin State-Trait Anxiety Inventory. Assessment of sleep quality and evaluation of insomnia severity were performed using the Insomnia Severity Index (ISI). Statistical data processing was performed using Statistica 10.0 software.

Results. In athletes practicing rhythmic gymnastics (p = 0.001), figure skating (p = 0.008), and softball (= 0.014), lower values of physical functioning were observed compared to representatives of other sports. In figure skaters, lower values of emotional (p = 0.005) and role functioning (p = 0.001) were recorded compared to athletes in other sports. In softball players, lower values of emotional (= 0.005) and role functioning (p = 0.001) were recorded compared to athletes in other sports. In figure skaters, the highest levels of trait and state anxiety were noted (p < 0.05).

Conclusions. Low scores of physical and emotional functioning were identified in athletes practicing figure skating, rhythmic gymnastics, and softball compared to representatives of other sports, as well as high levels of trait and state anxiety in female figure skaters, which allows them to be identified as a risk group during screening for quality of life impairments and anxiety levels. Further studies are needed to clarify the cutoff points of the questionnaires in the context of diagnosing quality of life and assessing trait and state anxiety in adolescent athletes, which will contribute to early detection of these impairments, improvement of quality-of-life, and reduction of anxiety levels within the framework of medical and biological support for high-performance sports.

TOXICOLOGY

118
Abstract

Introduction. Excessive growth of intestinal microbiota, acute dysfunction of the gut-blood barrier, and the subsequent endotoxemia are integral to the pathogenesis of critical illness. Heat stress was previously shown to potentiate the lethal effect of fentanyl in rats, accompanied by hyperammonemia. While literature suggests its intestinal origin, this hypothesis remains to be tested.

Objective. To identify the mechanisms of hyperammonemia induced by fentanyl and/or heat stress in rats.

Materials and methods. The study was conducted on outbred male albino rats (191–210 g). The animals were divided into the following groups: 22 °C (intact), Fentanyl + 22 °C (kept at room temperature after fentanyl administration), 40 °C (exposure to 40 °C in a thermal chamber for 40 min), and Fentanyl + 40 °C (exposure to 40 °C for 40 min following fentanyl administration). The first series of experiments evaluated the effects of fentanyl (200 μg/kg) and/or heat stress (40 °C) on 40-minute mortality, body temperature, and blood levels of ammonia, urea, creatinine, and lactate. The second series investigated the impact of these factors on the transperitoneal mass transfer of ammonia, urea, and creatinine. In the third series, the effects of the same factors on intestinal permeability were evaluated in vivo (based on transperitoneal transfer of intragastrically administered methylene blue). Fentanyl was injected at a dose of 200 μg/kg (4 mL/kg) into the lateral tail vein. Transperitoneal mass transfer of nitrogenous metabolites or methylene blue (MB) was calculated based on their accumulation over 40 min in 0.9% sodium chloride solution (30 mL/kg) administered intraperitoneally. Statistical analysis was performed using OriginPro software.

Results. Heat exposure or fentanyl administration alone was non-lethal, while their combination resulted in mortality rates of 44%, 33%, and 36% in the first, second, and third series of experiments, respectively. In response to heat stress, rectal temperature increased from 37.2 °C to 42.2 °C, reaching 43.6 °C under heat stress combined with fentanyl administration. Conversely, fentanyl alone caused a decrease to 32.8 °C. Animal body weight decreased by 4.4% in the 40 °C group and by 2.6% in the Fentanyl + 40 °C group. The combined effect of heat and fentanyl elevated blood ammonia levels from 132 ± 16 μM to 294 ± 24 μM. Blood urea levels under the influence of fentanyl, hyperthermia, or their combination increased from 3.4 ± 0.3 mM to 5.5 ± 0.7 mM, 7.1 ± 0.4 mM, and 6.8 ± 0.3 mM, respectively; creatinine levels increased from 38.8 ± 4.7 μM to 60.4 ± 3.9 μM under isolated hyperthermia and to 62.9 ± 3.5 μM under combined hyperthermia, respectively. Creatinine levels rose from 38.8 ± 4.7 μM to 60.4 ± 3.9 μM under heat stress alone and to 62.9 ± 3.5 μM under heat stress combined with fentanyl administration. The combined effect of heat and fentanyl increased the transperitoneal mass transfer of ammonia from 78 ± 6 to 168 ± 22 nmol/(kg × min) and that of MB from 83.6 ± 26.2 to 167.3 ± 29.2 pmol/(kg × min). Both heat exposure alone and when combined with fentanyl administration resulted in lactacidemia.

Conclusions. Fentanyl administration followed by heat exposure induced azotemia and lactic acidosis in rats. This combination also caused a synergistic increase in mortality, body temperature, blood ammonia levels, and transperitoneal ammonia transport from the intestine. The primary mechanisms underlying this potentially lethal hyperammonemia include fentanyl-induced enhancement of intestinal ammoniogenesis and heat stress-mediated increase in intestinal permeability.

GENETICS

49
Abstract

Introduction. Certain variants of the MAPT gene are associated with an increased susceptibility to developing Parkinson’s disease (PD). Among the candidate variants linked to PD are rs242557 and rs7521, for which a possible association with the development of PD in European populations, as well as a probable association with an early onset of the disease, have previously been shown.

Objective. To determine the frequency of the rs242557 and rs7521 genetic variants of the MAPT gene in populations of patients with Parkinson’s disease and healthy individuals, and to analyze their association with the overall risk of developing the disease and the age at disease onset.

Materials and methods. The study involved 62 patients with a confirmed diagnosis of PD (16 men and 46 women; mean age 62 ± 12 years). Among the 62 patients, 29 individuals (7 men and 22 women) had an early onset of PD (under 50 years; mean age 40 ± 7 years), and 33 individuals had a late onset of PD (50 years and older; mean age 61 ± 7 years). The control group consisted of 61 participants (24 men and 37 women; mean age 66 ± 17 years) without PD and with no family history of the disease. Preliminarily, all patients were analyzed for variants in the PARK2, PINK1, SNCA, ATP13A2, PARK7, LRRK2, UCHL, GCH1, and GBA genes associated with the development of PD. The rs8070723 (A and G alleles), rs242557 (G and A alleles), and rs7521 (A and G alleles) variants were analyzed by allele-specific real-time PCR using a CFX96 thermocycler. Allele-specific primers were designed independently using electronic resources and the Primer3, Vector NTI, and DNA Folding Form software. Statistical analysis was performed using Statistica 10 software.

Results. A statistically significant association between the homozygous AA genotype of the rs7521 variant with early onset of PD (p = 0.033) was established, and the association between the A allele of the rs7521 variant with early onset of PD approached statistical significance (p = 0.055). No statistically significant association was found between the H1 haplotype, the rs242557 and rs7521 variants, and PD, nor between the rs242557 variant and early onset of PD.

Conclusion. The frequencies of the rs242557 and rs7521 variants of the MAPT gene were determined in populations of PD patients and healthy individuals. The results of the study did not reveal a statistically significant association between the aforementioned variants and the development of PD; however, an association of the rs7521 variant with early onset of PD was found. The obtained data indicate a functional role of MAPT gene variants in the development of PD and warrant further investigation.

EMERGENCY RESPONSE ORGANIZATION

446
Abstract

Introduction. In some cases, fragment wounds are accompanied by damage to major arteries. The choice of a treatment strategy at the stage of military-field hospital сare determines the life prognosis of the serviceman.

Case description. A case of successful surgical treatment of a serviceman in a military field hospital is presented. The case involved a blind fragment wound to the thigh with avulsion of a branch of the deep femoral artery, which manifested 24 h after the initial surgical debridement of the wound and removal of a metallic shell fragment. An open surgery with ligation of the branch of the deep femoral artery with removal of the pulsatile hematoma was performed. The postoperative period proceeded without complications.

Conclusions. Convincing data on the necessity of conducting ultrasound examination of blood vessels in cases of fragment wounds in all instances, even in the absence of signs of hemorrhage, were obtained. In the case of a ruptured branch of the deep femoral artery, its ligation under the conditions of a military field hospital is an effective and safe method of surgical correction.

144
Abstract

Introduction. The development of a system for organizing health protection for workers at remote industrial sites (including high-altitude ones) is a relevant priority for both the Russian Federation and the Kyrgyz Republic. Due to the absence of unified standards in the remote health-care system, a priority is the analysis of principles and approaches in organizing an adequate and effective model of medical care delivery for personnel in these industrial production sectors.

Objective. Analysis and synthesis of data on the organization of medical care at remote industrial sites (RIS) in extreme high-altitude conditions.

Discussion. Labor activity at RIS in high-altitude conditions involves the impact on workers’ health of extreme climatic and geographic factors, adverse socio-psychological factors, as well as harmful and dangerous factors of the industrial environment, which necessitates the implementation of a specialized medical support system for workers. Medical care for RIS workers may be provided by the company’s own medical service or by hired medical service providers (outsourcing). In the Kyrgyz Republic, all mining enterprises have their own medical services. The medical service at a high-altitude RIS consists of two units: the main medical station of the RIS (paramedic or physician-staffed) and a medical station at the central checkpoint. A distinctive feature of the medical station’s work in high-altitude conditions is the high number of patient visits for acute mountain sickness (AMS). For example, among shift workers at a mining enterprise in the Kyrgyz Republic at an altitude of 3800 m, the AMS incidence was 25%. The main approaches to AMS preventing in the general worker population are altitude acclimatization, pharmacological support, rehydration, prevention of electrolyte imbalances, protection against light-induced eye and skin damage, and prevention of cold injury. For further medical care provision to workers with AMS, a two-stage evacuation system is used when the RIS is located at an altitude above 3500 m and at a significant distance from populated areas, which involves establishing an intermediate medical station at an altitude of 1700–1800 m above sea level.

Conclusions. Medical support for shift workers in extreme high-altitude conditions is part of a developing field — remote healthcare. The issues of organizing medical care at remote industrial sites in mountainous areas are relevant due to the intensive development of the mining industry in the Kyrgyz Republic. The need is shown for special training of medical personnel in remote healthcare, improvement of the regulatory framework governing the procedures and algorithms for providing medical care to RIS workers, in order to enable the construction of a new model of medical support that complies with unified standards of medical care, including through the introduction of telemedicine and mobile components.

66
Abstract

Introduction. Modern combat trauma, especially mine‑blast extremity injuries, often results in severe combined injuries with near-complete avulsions, critical ischemia, and extensive tissue defects. The relevance of limb salvage is determined by medical and socio‑psychological aspects. However, the implementation of complex reconstructive techniques in a field military hospital setting is associated with extreme factors and requires adaptation of the “damage control” principles (Damage Control Surgery).

Objective. To analyze a comprehensive surgical approach to limb salvage in cases of near-complete traumatic hand amputation complicated by vascular insufficiency, using a clinical case example in a level 2 field military hospital.

Case description. A clinical case of a mine-explosive injury to the left upper extremity in a 38-year-old serviceman is presented. The injury involved near-complete avulsion of the hand, comminuted fractures of the forearm bones, an extensive soft tissue defect, and critical ischemia. Treatment involved a multidisciplinary consultation and the execution of the following in a single surgical series: 1) extensive primary surgical debridement of the wound, 2) external fixation of the radius using a military external fixation kit, 3) microsurgical autovenous grafting of the radial artery with a reversed graft from the great saphenous vein of the leg. Intraoperative monitoring was performed using pulse oximetry and ultrasound angioscanning. As a result of the operation, main arterial blood flow to the hand was restored (pulsation in the radial artery, SpO2 90% on the finger, blood flow velocity in the superficial palmar arch 100 cm/s according to ultrasound angioscanning). The condition of the limb improved postoperatively: the hand became warm and pink. After 4 hours, the patient was evacuated for further staged treatment. Successful early revascularization was made possible by the sequential combination of Damage Control Surgery principles (radical primary surgical debridement and minimally invasive fracture stabilization) and complex microsurgical reconstruction. Key success factors included the short ischemia time, a carefully considered decision by the consultation, and the selection of a distant (lower leg) donor site for vein graft harvesting to reduce the risk of infection and preserve venous outflow in the injured limb. This case demonstrates the possibility of bringing elements of specialized surgical care to more forward stages of medical evacuation in modern armed conflicts.

Conclusions. This experience demonstrates that limb salvage in severe combat injuries with a vascular component is possible at the stage of qualified surgical care (Level 2 hospital), provided there is a multidisciplinary approach, readiness to perform microsurgical interventions, and strict adherence to the principles of staged treatment. The success of initial revascularization is critically important, but represents only the first step in a long process of subsequent reconstructive and rehabilitative measures aimed at restoring function.

104
Abstract

Introduction. Combined fragment wounds of the chest and abdomen are among the most severe types of combat trauma. Injuries to the inferior vena cava (IVC) and renal vessels are associated with massive retroperitoneal hemorrhage and high mortality rates, reaching 50–70%. In a mobile medical group (MMG) (Level 2+ of medical care), located close to the combat zone, treatment success depends on rapid decision‑making, a well‑organized multidisciplinary approach, and the performance of complex vascular reconstructions.

Case description. A 32‑year‑old serviceman was delivered to the MMG 30 min after sustaining a fragment wound. The condition was extremely severe, characterized by profound hemorrhagic shock grade II and severe anemia. A penetrating abdominal wound with injury to the right kidney and retroperitoneal hemorrhage, as well as a right‑sided pneumothorax, were diagnosed. The consultation team decided on emergency surgery. Pleural cavity drainage and a midline laparotomy were performed, revealing a massive retroperitoneal hematoma (2 L of blood evacuated). Exploration demonstrated an injury to the right renal hilum with avulsion of the renal artery and vein, alongside two defects of the IVC: avulsion of the right renal vein from its confluence and a through‑and‑through defect of the anterior wall. After intravenous heparin administration, the IVC was clamped, the vein defects were closed with a parietal suture, and the renal vein stump was oversewn. Due to fragmentation of the renal hilum, a right‑sided nephrectomy was performed. The operation was completed with a laparostomy. Intraoperative hemotransfusion amounted to 2000 mL of blood components. The postoperative condition was stable, and the patient was evacuated to a rear hospital.

Conclusions. This case demonstrates the possibility of successfully providing specialized surgical care to wounded patients with critical major vessel injuries in a MMG (Level 2+ of medical care). The key success factors were rapid evacuation, coordinated work of a multidisciplinary team, correct choice of damage control tactics with temporary hemostasis and subsequent vascular defect closure under systemic heparinization.

ARCTIC MEDICINE

200
Abstract

Introduction. Prolonged stay in the Far North imposes significant stress on the body’s adaptive mechanisms responsible for maintaining homeostasis. In this context, the nutrition of military personnel based on a scientifically ground system that ensures optimal intake of essential nutrients, including micronutrients, plays an important role in the acclimatization process. Proper dietary provision preserves and strengthen the health of military personnel, preventing the development of chronic adaptive stress.

Objective. Assessment of the adaptation state of military personnel in the Arctic following inclusion of a natural product rich in dietary and biologically active substances in their diet.

Materials and methods. The study was conducted in June–July 2022 in the Arctic, involving healthy and practically healthy male military personnel (n = 60; mean age 37.3 ± 3.1 years). The median duration of professional activity was 7.0 [5; 9] years. The subjects were divided into the following groups. The main group (n = 30) received 10.0 g of a plant protein product (PPP) incorporated into the main dinner meal for 21 days, whereas the comparison group (n = 30) was provided with a standard ration. The formulation of the PPP was developed considering the living conditions. The PPP included: chokeberry (aronia), flax seeds, carrots, broccoli, seaweed, and chicken eggshell. The amount of macro- and microelements, dietary fiber, and minor biologically active substances included in the PPP was calculated. The assessment of the body’s adaptation state was performed by analyzing leukograms. A complete blood count was performed using an automated hematology system (Abbott, USA). The types of non-specific adaptive reactions of the body, levels of reactivity, and adaptation status in the main group prior to and following administration of the PPP, as well as in the comparison group at baseline and on day 22 of the experiment, were determined using L. Garkavi’s method. Statistical processing of the initial data was performed using the IBM SPSS Statistica 6.1 software package.

Results. In individuals of the main group, a decrease in leukocyte counts from 6.52 ± 0.61 to (6.3 ± 0.47) × 109/L was detected, along with an increase in the number of eosinophils, monocytes, lymphocytes, and the percentage of band neutrophils. At baseline, in 2 (6.7%) participants from the main group, the type of adaptive reaction was classified as “enhanced activation,” while in 14 (46.7%) individuals it was defined as “training” and “calm activation.” By the end of the 22-day observation period, 28 (93.3%) subjects from the main group demonstrated the body’s adaptive reactions classified as “enhanced activation,” except for 2 (6.7%) individuals whose adaptive reaction type was assessed as “calm activation.” Prior to PPP intake, the level of body reactivity was assessed as high and medium in the majority of subjects. After 22 days, only one person in the main group had a medium level of reactivity, while all others were assessed as having a high level with the “enhanced activation” type of adaptive response. In individuals with the “calm activation” type, the level of reactivity was statistically significantly high in all cases. Following the PPP course in the main group, adaptation was assessed as being within a physiological norm in all servicemen. The comparison group, conversely, showed an increase in the proportion of individuals in a pre-nosological state.

Conclusions. It was established that in the absence of extreme cold exposure (as the study was conducted in the Arctic during the summer period), the non-specific adaptive mechanisms of the body in individuals of the main group and the comparison group were predominantly assessed as “training” (46.7–56.7%) and “calm activation” (36.7–43.3%), corresponding to high and medium levels of body reactivity. Nutritional optimization with the inclusion of PPP in the subjects of the main group contributed to stimulating metabolic processes in the body, a positive shift in lymphopoiesis (manifested in an increase in the proportion of individuals with the “enhanced activation” type of non-specific adaptive reaction to 93.3% in the main group), and the restoration of the adaptation state to the physiological norm.

90
Abstract

Introduction. The complex of unfavorable natural and climatic factors in the North, creating a stressful living environment, induces a pronounced tension in the immune responses that maintain homeostasis. Determining the type of adaptation reaction and the level of reactivity makes it possible to diagnose the functional state of the body and predict its response patterns to environmental factors.

Objective. Determination of systemic inflammation biomarker levels, calculated based on complete blood count data, for assessing the stress and failure of the adaptation process.

Materials and methods. The study examined 178 practically healthy volunteers (136 women and 42 men; mean age 31.17 ± 0.85 years). The assessment of the body’s adaptation state was carried out by analyzing leukograms. The types of non-specific adaptation reactions, levels of body reactivity, and adaptation state were determined according to Garkavi’s method. According to this method, all subjects were divided into the following groups: “physiological norm” (group 1) — 68 women and 23 men, mean age 31.59 ± 1.29 years; “adaptation stress” (group 2) — 50 women and 10 men, mean age 31.21 ± 1.15 years; “adaptation failure” (group 3) — 18 women and 9 men, mean age 28.17 ± 2.51 years. General short-term cold exposure was modeled once in a climatic chamber (USHZ-25N, Russia), in which the subjects, dressed in cotton clothing, remained under continuous video observation for 5 min at an ambient air temperature of –25 °C. Hematological studies were performed using an XS-500i analyzer. The content of catecholamines, cortisol, PPARγC1α, HIF‑1α, SIRT3, and BPI was determined by ELISA. Lymphocyte apoptosis and necrosis were assessed by double staining with Annexin V and propidium iodide (AnV/PI). The quantitative content of ATP was determined using the luciferin‑luciferase method. The following systemic inflammation indices were calculated: systemic immuneinflammation index (SII), systemic inflammation response index (SIRI), and aggregate index of systemic inflammation (AISI). The results were processed using StatTech v.4.9.2 and Statistica 6.0 software.

Results. In the “physiological norm” group, an increase in leukocyte counts, enhanced cell migration activity, and improved mitochondrial energy supply for their functional activity indicated high non-specific resistance and the absence of a stress effect from this type of cold exposure. Under “adaptation stress”, the fastest cardiovascular responses aimed at maintaining temperature homeostasis were recorded, accompanied by increased catecholamine levels, enhanced leukocyte recirculation and migration, allowing the body to respond rapidly to short‑term stress factors. In the “adaptation failure” group, the baseline tension in the activity of regulatory systems, even after a single short‑term cold exposure, did not lead to the activation of effective thermoregulation mechanisms; leukocyte migration activity was slowed, significantly increasing the risk of maladaptive and pro‑inflammatory reactions. It was established that SIRI, SII, and AISI are significant risk criteria for adaptation strain at SIRI ≥ 0.97, SII ≥ 447.43, AISI ≥ 216.24, and for adaptation failure at index values of ≥1.23, ≥449.76, and ≥239.58, respectively.

Conclusions. “Adaptation stress” and “adaptation failure” are characterized by changes in cellular and humoral parameters of peripheral blood even before the clinical manifestation of the disease, and these changes may be exacerbated by additional exposure to negative factors, even if their impact is short‑term. Baseline systemic inflammation indices (SIRI, SII, AISI) are significant predictors for assessing both “adaptation stress” and “adaptation failure”. The use of these indices, calculated from complete blood count results, will make it possible to assess the presence of an initial imbalance in the body’s adaptation mechanisms, which may subsequently be aggravated by exposure to stress factors.

BIOMEDICAL RESEARCH

166
Abstract

Introduction. Early diagnosis of malignant tumors, including those of lymphoid and hematopoietic tissues, is paramount for improving prognosis and survival outcomes. A key strategy for early detection involves the use of sensitive and specific biomarker-based screening tests. The identification of such biomarkers and the subsequent development of novel diagnostic assays can be achieved through the study of large-scale biorepositories.

Objective. To evaluate the feasibility of identifying early preclinical immune markers of B-cell lymphoproliferative disorders in retrospective studies drawing on data from global population-based biobanks.

Discussion. The most frequently identified early preclinical markers for non-Hodgkin lymphomas include sCD23, sCD27, sCD30, and CXCL13, along with several cytokines and their receptors, such as IL-10, TNF-α, sTNF-R2, and sIL-2Rα. In multiple myeloma, early preclinical markers comprise IL-10, MIP-1α, VEGF, and TGF-α. Notably, these biomarkers can be detected more than a decade prior to the clinical onset of B-cell lymphoproliferative disorders. Research into the association between these markers and cancer has been facilitated by population-based biobanks, which enable retrospective analysis following clinical diagnosis. Notable examples include the Janus Serum Bank (Norway), the PLCO biorepository (USA), the UK Biobank (United Kingdom), and repositories in Sweden and other countries.

Conclusions. Analysis of population-based biobank materials represents an effective tool for identifying associations between immune markers and cancer prognosis, thus facilitating the development of novel methods for early diagnosis. The proven success of global biorepositories demonstrates the potential for advancing biobanking infrastructure in Russia, as well as the need for fostering integration and collaboration with leading international institutions.

TOXICOLOGY & CLINICAL PHARMACOLOGY

101
Abstract

Introduction. Replacement of acute blood loss in trauma is an essential component of emergency care. The use of low-volume hyperosmolar dextran-based solutions may be an effective means of restoring hemodynamics and improving survival while minimizing the risks associated with conventional volume-based resuscitation.

Objective. Comparison of the effectiveness of resuscitation measures after administration of an experimental hyperosmolar dextran-based infusion solution at doses corresponding to 1/2 and 1/6 of the circulating blood volume (TBV) in a porcine model of acute blood loss.

Materials and methods. Experiments were conducted on outbred male pigs (n = 18) weighing 47.7 ± 3.4 kg, which were divided into 3 groups: a control group (blood loss without treatment) and two experimental groups (S-1 and S-2), in which animals, after exsanguination of 45–50% of their blood, received an experimental dextran-based infusion solution (1026.6 mOsm/L) at doses corresponding to replacement of TBV in blood loss replacement ratios of 1/2:1 and 1/6:1. Acute blood loss was modeled by exsanguination from the left femoral artery using a “Gemma” plasmapheresis device. The following parameters were recorded in the animals (ADC, L-Card, Russia): mean arterial pressure (MAP), heart rate (HR), respiratory rate (RR); biochemical parameters of blood gas tensions and acid-base status (i-STAT System, Abbott, USA) were assessed before blood loss, after the period of blood loss, and at 5, 30, 60, 120, 180 min, and 24 h after completion of the infusion. Statistical analysis was performed using Statistica 10.0 software.

Results. Acute blood loss exceeding 45% of TBV led to a decrease in MAP to 35–40 mmHg (p < 0.001), an HR increase by 35–50% (p < 0.001), reduced blood pH to 7.30–7.32 (p < 0.01), and increased lactate levels to 6.5 [6.4; 8.4] mmol/L (p < 0.001). The absence of treatment led to the death of 75% of animals. Infusion of the studied solution increased MAP to baseline levels, stabilized HR parameters, halted the development of lactic acidosis, and ensured 100% survival of treated animals. The equally high efficacy of the experimental solution at both replacement doses indicates an advantage of using low-volume infusion at a replacement dose of 1/6 of blood loss.

Conclusions. Simulated resuscitation measures in pigs after acute blood loss exceeding 45% of TBV, using infusion of an experimental hyperosmolar dextran-based infusion solution, provided 100% animal survival, contributed to an increase in blood pressure to baseline levels, stabilized HR parameters, and halted the development of lactic acidosis. Low-volume resuscitation using a hypertonic saline solution in combination with dextran may have significant practical advantages in providing emergency medical care to victims of acute massive blood loss, including in regions with extreme climates.

113
Abstract

Introduction. In Russia, venomous snakes are mainly represented by species from the viper family. Several thousand people suffer from viper bites each year in Russia; a small proportion of these cases are fatal, primarily due to cardiovascular causes. There is no study of this issue in the Russian medical literature, and the national clinical guidelines in cardiology do not mention the toxic effects of viper venom on the heart.

Objective. To systematize data on the toxic effect of venom from snakes of the Viperidae family on the human myocardium.

Methods. A systematic review of cases was conducted in accordance with the PRISMA 2020 criteria. The search was carried out in the electronic databases PubMed, Google Scholar, and eLibrary. The review included 30 publications (29 case reports and 1 case series) that met the inclusion and exclusion criteria. From each publication, the following data were extracted: country of the case, demographic data, vital signs, clinical presentation, laboratory and instrumental parameters, condition of the coronary arteries, outcomes, and therapy administered.

Results. Twenty-two cases of myocardial infarction (MI) (71%) were analyzed, 17 of which (77.3%) were ST-segment elevation MIs, and 9 cases of toxic myocarditis (TM) (29%). Seventy-one percent of the affected individuals had no prior medical history. Systolic blood pressure (SBP) in the MI group was statistically significantly lower than in the TM group (p = 0.0344). The median time from the bite to the onset of anginal pain in the MI group was 5.0 [0.3; 240] h. Signs of hypocoagulation were observed in 75% of cases, and leukocytosis (always neutrophilic) was present in 82.6% of cases. Significant T-wave changes were found in 26.6% of patients, predominantly as T-wave inversion in the chest leads, occurring in both the MI and TM groups. In MI cases, ST-segment elevation was recorded in 77.3%; among these, criterion ST-segment elevation was in the anterior leads in 52.9% and in the inferior leads in 47.1%. Ventricular tachycardia was detected in 2 patients, both with MI. In one TM case, severe atrioventricular block occurred, requiring implantation of a permanent pacemaker (PPM). Echocardiographic changes were documented in 55% of cases, with global hypokinesis observed in 18.2% of TM cases. The median left ventricular ejection fraction was 56.0 [40.0; 62.0]% for MI and 37.5 [30.0; 45.0]% for TM (p = 0.0858). In 8 cases (62.5% MI and 37.5% TM), the coronary arteries were intact according to coronary angiography; in 5 cases (100% MI), a large mural thrombus was visualized; and in 1 MI case (a 74-year-old patient), significant atherosclerotic coronary artery disease was found. Thrombolysis with reteplase and tenecteplase was performed in 11.8% of cases of ST-segment elevation MI. Dual antiplatelet therapy was administered to 40.9% of patients with MI. Blood component transfusion was required in 22.6% of cases to correct coagulation disorders. Hemodialysis was mentioned in two publications, both in MI cases. Clinical death occurred in 25.8% of the affected individuals immediately after the snake bite or upon admission. Overall mortality was 22.7% for MI and 22.2% for patients who developed TM.

Conclusions. Cardiovascular complications after viper bites are rare but can have a wide range of outcomes, including cardiac arrest, malignant ventricular arrhythmias, the need for pacemaker implantation, blood component transfusion, hemodialysis, and death. The management of this group of patients, including the use of antivenom, remains a topic for future research.

125
Abstract

Introduction. We previously observed that general hyperthermia potentiates the lethal effect of fentanyl in rats. However, the relationship of this phenomenon to indices of vital functions of the organism remains unclear.

Objective. To identify the specific effects of fentanyl on body temperature, blood cell composition, and circulation in rats under heat stress conditions.

Materials and methods. The study was conducted on outbred male albino rats (191–210 g). Two series of experiments were performed on two separate animal samples, each of which was divided into the following groups: “22 °C” (intact), “Fentanyl + 22 °C” (kept at room temperature after fentanyl administration), “40 °C” (placed in a thermal chamber at 40 °C air temperature for 40 min), and “Fentanyl + 40 °C” (placed in the thermal chamber after fentanyl administration). In the first series of experiments, the effect of fentanyl (200 μg/kg) and/or exposure of rats to 40 °C air temperature on mortality over 40 min, body temperature, hemogram parameters, electrocardiogram (ECG), and blood pressure (BP) was studied. In the second series, the effect of fentanyl and/or heat stress on kidney weight, water content, and histological parameters of renal blood filling was studied. Heat stress was modeled by placing perforated restrainers with animals in a thermal chamber for 40 min. Fentanyl solution was administered at a volume of 4 mL/kg and a substance dose of 200 μg/kg into the v. caudalis lateralis. Statistical analysis was performed using OriginPro software.

Results. Isolated exposures were non-lethal, whereas their combination resulted in a mortality rate of 50% in the first series and 38% in the second series of experiments. After fentanyl administration, the following significant (p < 0.05) differences compared to the control groups were observed. Rectal temperature decreased by 5.6 °C at 22 °C but increased by 5.7 °C at 40 °C. At 22 °C, fentanyl decreased the heart rate of rats by 48%, whereas at 40 °C it increased heart rate by 25%. At 22 °C, fentanyl prolonged the RR interval by 90%, while at 40 °C it shortened the RR interval by 23%. In rats that died in the thermal chamber, the relative wet weight of the kidney was increased by 27% and the relative dry weight by 20%. At 40 °C, but not at 22 °C, fentanyl reduced blood leukocyte count by 47% and platelet count by 33%, increased renal cortical blood filling, activated the juxtamedullary shunt, and induced intravascular hemolysis.

Conclusions. For the first time, it has been established that under heat stress, the effects of fentanyl on body temperature, autonomic balance, and cardiac automaticity are opposite to those observed under thermal comfort. The fentanyl-induced changes in hemogram parameters, BP, and renal blood filling at 22 °C and 40 °C differ in magnitude. These fentanyl effects under hyperthermia represent early manifestations of exotoxic shock.

AVIATION & SPACE MEDICINE

201
Abstract

Introduction. Due to exposure to a set of extreme factors, prolonged ground-based isolation simulating a space mission induces various adaptive responses in the body. The study of such organismal responses at the molecular level is important for the development of high-quality medical support plans for subsequent space missions. Proteomic methods have proven effective for assessing the molecular mechanisms of adaptation.

Objective. To study the profile of proteomic physiologically active components in the blood of test subjects as criteria for adaptive strategies of physiological systems in response to exposure to extreme factors of prolonged isolation during ground-based simulation of spaceflight factors.

Materials and methods. The characteristics of proteomic physiologically active blood components were studied in six healthy volunteers aged 27–38 years (mean age 32.5 ± 5.5 years) under the conditions of a 12-month isolation (SIRIUS-23) in a hermetically sealed facility with limited living and working space and restricted resources for life support. Mass spectrometry methods were used to analyze dried blood spot samples. Statistical analysis was performed using the Statistica 12 software with non-parametric Mann–Whitney U test (p < 0.05). The biological processes involving the identified proteins were determined using the STRING database.

Results. Following one month of isolation, a significant increase in the expression of three proteins involved in the biological process of phagocytosis suppression was observed. Following three months of isolation, the concentration level of 22 extracellular matrix and exosome proteins significantly increased. Following six months of isolation, the concentration of 33 proteins involved in either cellular component processes or regulation of extracellular signaling significantly increased.

Conclusions. The data obtained allowed us to compile a preliminary version of biological processes, which involve proteins with reliably changing concentrations, during prolonged isolation in a specialized facility. The conducted study elucidates the proteomic mechanisms regulating biological processes in healthy individuals during the simulation of spaceflight factors.

95
Abstract

Introduction. Recently, women have increasingly participated both in ground-based model experiments simulating specific spaceflight factors and in actual space missions. During spaceflight, the human body is exposed to various factors that may pose health risks. When modeling various spaceflight factors, the human microbiota undergoes adverse changes: the proportion of opportunistic microorganisms increases, while the abundance of protective microorganisms decreases. Pronounced changes also occur in the blood protein profile. The relevance of this study is due to the close relationship between the blood protein profile and the composition of the vaginal microbiota; disruptions in the microbiota can affect protein metabolism and biochemical parameters of the body, provoking the development of pathologies.

Objective. To identify the relationship between the blood proteome and the bacteria of the vaginal biotope in participants of a 5-day dry immersion experiment.

Materials and methods. Seven female volunteers of reproductive age (mean age 29 ± 1 years) participated in the dry immersion study. The participants did not receive antibacterial treatment during the experiment. The subjects were divided into two groups: the L + P group (n = 3) consumed a lactoferrin-based drink (200 mg/day) together with intravaginal glucose-based placebo suppositories; the P + P group (n = 4) consumed a placebo preparation (200 mg glucose) and intravaginal maltodextrin placebo suppositories (200 mg/day). Vaginal and endocervical swab samples were collected twice: before the start of the experiment and 5–7 days after its completion, with smear collection synchronized to days 19–22 of the menstrual cycle. For each participant, vaginal smear microscopy was performed, and microorganisms were identified to species level using MALDI-TOF MS analysis. Blood samples for proteomic analysis were examined by liquid chromatography and mass spectrometry. Statistical analysis was performed using STATISTICA 12.0. The STRING.DB platform was used to identify clusters among the proteins extracted from factor analysis.

Results. Proteomic analysis of dried blood spot extracts allowed identification of 818 distinct proteins. Using factor analysis before the start of dry immersion, seven factors were extracted (according to the Kaiser–Meyer–Olkin criterion, only data with KMO ≥ 0.7, indicating acceptable, good, or excellent suitability for factor analysis, were included). Analysis of the extracted factors showed that before dry immersion, the association between blood proteins and bacteria was determined by the following processes: ubiquitination (37.9% of variance), immune responses (12.3% of variance), and hormonal status (13.7% of variance). After completion of the experiment, the key processes in the protein-bacterium relationship became ubiquitination (37.1% of variance in the P + P group), immune mechanisms (43.88% of variance in the L + P group), and estradiol synthesis (56.12% and 33.5% of variance in the L + P and P + P groups, respectively). The following microorganisms showed the greatest sensitivity to proteins associated with estradiol: Lactobacillus spp., Corynebacterium spp., Staphylococcus spp., and Cutibacterium spp.

Conclusions. Before and after dry immersion, the interaction between blood proteins and bacteria was determined by ubiquitination and immune processes. After the experiment, the relationship within the protein-bacterium system became stronger, and the microorganisms most sensitive to proteins involved in estradiol processing were representatives of Lactobacillus spp., Corynebacterium spp., Staphylococcus spp., and Cutibacterium spp. This suggests the possibility of strengthening the colonization resistance of the vaginal microbiota through targeted modulation of specific biological processes in the body.

105
Abstract

Introduction. Long-duration space flights are accompanied by significant changes in iron metabolism, characterized by accumulation of ferritin, decreased serum Fe3+ and transferrin concentrations, and the development of signs of “space anemia”. Excessive iron deposition can impair bone and muscle metabolism, weaken immunity, and increase sensitivity to radiation. Serum iron levels are tightly regulated through modulation of intestinal absorption, macrophage recycling, mobilization of tissue stores, and erythropoiesis, involving key hormones — hepcidin and erythropoietin. Understanding the regulatory mechanisms of iron metabolism and erythropoiesis is necessary to develop measures for anemia prevention in future interplanetary missions.

Objective. Assessment of the dynamics of hepcidin, erythropoietin (EPO), C-reactive protein (CRP), and erythropoiesis markers in the blood of cosmonauts during the early recovery period (RP) after space missions of varying duration on the International Space Station.

Materials and methods. A total of 40 male cosmonauts were examined, divided into three groups according to mission duration: Group A — 8–14 days (n = 9), Group B — 125–215 days (n = 27), Group C — 340–371 days (n = 4). Venous blood was collected 45–30 days before the flight and on days 1 and 7 of the RP. CRP level was determined by immunoturbidimetry; hepcidin and EPO concentrations were determined by enzyme-linked immunosorbent assay. Statistical analysis was performed using the Shapiro–Wilk, Wilcoxon, Friedman, and Spearman correlation tests. Differences were considered significant at p < 0.05.

Results. On RP day 1, CRP levels were significantly elevated in all cosmonauts, while hepcidin levels were decreased (statistically significantly in Group A). On day 7, EPO levels were significantly increased in cosmonauts of Group B. Correlation analysis revealed an inverse relationship between erythrocyte count and total time spent in low Earth orbit, as well as positive correlations between mission duration and red blood cell distribution width, and between mission duration and mean erythrocyte volume.

Conclusions. Spaceflight factors and the stress response during post-flight readaptation provoke non-specific inflammation, leading to redistribution and deposition of iron in tissues. Activation of stress erythropoiesis is one of the main factors facilitating the release of iron for hemoglobin synthesis in the early RP. The magnitude of changes in the erythropoiesis system depends on the duration of orbital missions.

HEMATOLOGY AND TRANSFUSIOLOGY

128
Abstract

Introduction. Platelet activation and vesiculation processes negatively affect the functional state of platelets and can accelerate cell apoptosis in platelet concentrates (PCs). Platelet-derived microparticles (PMPs) are biologically active vesicles formed as a result of platelet activation or apoptosis. PMPs can be considered as a marker for predicting the functional properties of PCs.

Objective. Assessment of the role of PMPs to the formation of functional and procoagulant activity of PCs.

Materials and methods. The study included 20 regular platelet donors. The PMP level in peripheral blood and PCs was determined by flow cytometry. Aggregation activity in PCs was assessed using adenosine diphosphate (ADP), collagen, and ristocetin as inducers. During thromboelastography, the following parameters were analyzed: clot formation time (R), maximum amplitude, and clot elasticity index. Statistical analysis was performed using the Mann–Whitney U-test, Wilcoxon test, and Pearson correlation.

Results. The PMP level in donor blood was not significantly associated with sex, age, or donor tenure. During storage, the PMP level in PCs increased 3.5-fold (p < 0.0001). Platelet aggregation activity decreased by day 5, especially in the presence of ADP and collagen. Thromboelastography parameters also decreased, which may indicate a reduction in hemostatic potential. An inverse correlation was found between PMP levels and the increase in clot formation time (R = –0.490; p = 0.028).

Conclusions. PMPs can serve as a marker of platelet activation and the PCs quality. No statistically significant correlations were found between individual donor characteristics and PMP levels, suggesting that technological factors of blood component collection and processing have a dominant influence on the microparticle formation process. The patterns of PMP level in peripheral blood are of substantial scientific interest in the context of developing new quality control parameters for platelet-containing components.

REGENERATIVE BIOMEDICINE

30
Abstract

Introduction. In modern medical practice, bone implants are in demand as an effective solution for restoring bone tissue, including for the rehabilitation of patients with wounds sustained in combat. Polyetheretherketone (PEEK) is considered a promising polymer material for surgical implant production due to a number of properties that closely mimic bone tissue. However, the use of unmodified PEEK in implantology is limited by its biological inertness and poor osseointegration. Modification of this material, including through structural changes to the surface, can increase its biological activity, osteoconductivity, and antibacterial properties.

Objective. To evaluate the cytotoxicity and surface adhesion properties of PEEK modified via various methods.

Materials and methods. PEEK powder was synthesized via polycondensation under nucleophilic substitution conditions by reacting hydroquinone with 4,4’-difluorobenzophenone; for further studies, disk-shaped specimens were fabricated via milling. PEEK surface was modified using one of three methods: sulfonation with concentrated sulfuric acid, treatment with piranha solution followed by functionalization with glycine, or high-temperature fusion with NaCl followed by leaching. The structure of the obtained materials was studied using IR spectrometry and scanning electron microscopy. Cytotoxicity was assessed using the MTT test. The adhesive properties of PEEK materials were evaluated by culturing human dermal fibroblasts on their surface, followed by fluorescence visualization using Calcein AM and Hoechst 33342 fluorochromes. Analysis of adhesion and morphology of attached cells was performed using an inverted Leica DMI 3000 B microscope.

Results. It was shown that PEEK obtained via polycondensation of hydroquinone and 4,4’-difluorobenzophenone does not exhibit a cytotoxic effect on anchorage-dependent cells. Under the influence of the 1-day extract of PEEK and its dilutions, relative cell viability ranged from 96 to 126%, while for the 7-day extract, it varied from 132 to 141% (vs. 100% for the control); stimulation of proliferative activity of cells by PEEK extract was demonstrated. It was found that modification of the specimens does not lead to increased cell adhesion. The porous PEEK specimen obtained by pressing with NaCl followed by its leaching was characterized by uneven adhesion and impaired viability of most cells on the specimen surface. Treatment of PEEK with glycine led to decreased adhesion, impaired viability, and altered morphological characteristics of a large proportion of cells on the specimen surface. On the surface of sulfonated PEEK, the cells remained viable; however, the morphology of the attached cells differed significantly from the typical pattern. Specifically, instead of a subconfluent monolayer of flattened cells characteristic of successful adhesion, cell conglomerates of various sizes, formed by rounded and, less frequently, spindle-shaped cells, were unevenly distributed across the surface.

Conclusions. When modifying PEEK via sulfonation with concentrated H2SO4, treatment with glycine, or high-temperature fusion with NaCl, no improvement in the biocompatibility of the material was detected; on the contrary, impairments in the viability and morphology of anchorage-dependent cells adhered to the surface of the modified PEEK were observed. These findings highlight the need to continue searching for PEEK modification methods to overcome the limitations of the material and expand its areas of application in solving urgent interdisciplinary biomedical problems.

DIAGNOSTICS & PROGNOSIS

245
Abstract

Introduction. Modern critical care medicine focuses on integrative real-time monitoring that combines the assessment of hemodynamics, autonomic regulation, and metabolism to enable early detection of risks and optimization of therapy. However, despite technological advances, there remains a high demand in routine intensive care practice for the systematization of information precisely on those parameters that remain amenable to rapid measurement, evaluation, and treatment adjustment during ongoing patient observation, regardless of the specific equipment available in a given hospital.

Objective. Determination of the feasibility of using non-invasive methods for assessing hemodynamics, autonomic tone, and laboratory biomarkers for prognosis and proactive risk management.

Materials and methods. This systematic review was conducted in accordance with the PRISMA 2020 guidelines. A search was performed using Google Scholar, as well as the bibliographic databases PubMed/MEDLINE, RSCI (eLIBRARY), CyberLeninka, and the ClinicalTrials.gov registry for the period 2010–2025. Original research and systematic reviews addressing non-invasive hemodynamic monitoring, assessment of the diastolic shock index (DSI), the heart-rate-to-body-temperature ratio (HR/T), as well as blood lactate levels and lactate clearance in adult patients admitted to intensive care units were included. Due to heterogeneity among the studies, a qualitative data synthesis was performed.

Discussion. Technologies of non-invasive hemodynamic monitoring (the unloaded artery method, bioreactance, thoracic bioimpedance spectroscopy) and prognostic indices were reviewed. A DSI > 2.2 mmHg/min has been shown to be an independent predictor of mortality in septic shock, particularly when used with dynamic assessment and combined with lactate levels. A HR/T > 20.5 bpm/°C reflects impaired autonomic regulation and is associated with an unfavorable outcome in sepsis, complicated infectious diseases, and heart failure. Failure to achieve lactate clearance (< 10% over 6 h) is more informative than its initial level and serves as a key metabolic marker. The greatest predictive utility is achieved through multi-parameter data integration.

Conclusions. The modern approach to monitoring in intensive care should be multidimensional and dynamic. The complementary use of non-invasive hemodynamic monitoring, simple calculated indices (DSI, HR/T), and biomarkers (lactate) enables the creation of an integrated predictive model of the patient’s condition. Promising directions for the development of monitoring include the personalization of threshold values and the integration of data into clinical decision support systems.



Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.


ISSN 3033-8964 (Print)
ISSN 3033-8972 (Online)