Objective . To evaluate the relationship between immunological parameters and functional outcome in patients with varying severity of ischemic stroke based on statistical methodology. Materials and methods. The prospective study included 78 patients diagnosed with ischemic stroke, who were distributed into two groups: group 1 — 38 mild stroke patients, NIHSS score < 5, group 2 — 40 moderate stroke patients, NIHSS score 5–15. Signs of stroke severity, degree of disability, cognitive decline, and activities of daily living were chosen as criteria to estimate the functional outcome by calculating the difference between the NIHSS, mRS, MoCA, and BI scales at the time of admission and on Day 12 of hospital stay. Lab tests included assessment of plasma concentrations of CXC and CC subfamilies of cytokines, interleukins and TNF-a on Day 2 of hospital stay. Machine learning algorithms, the Python programming language, the Pandas and SciPy libraries, and discriminant analysis were used for statistical processing. Results. The following parameters were found as significant: concentrations of IL-1b and MPIF-1/CCL23 for — for group 1, and concentrations of IL-16, MPIF-1/CCL23, Eotaxin-2/CCL24, Gro-a/CXCL1 and IL-8/CXCL8 for group 2 patients. Positive correlation was established between NIHSS dynamics and concentrations of TNF-a ( R =0.227, P =0.001), MPIF-1/CCL23 ( R =0.380, P =0.00061) and Gro-a/CXCL1 ( R =0.211, P =0.00001), and between changes in mRS and concentrations of MPIF-1/CCL23 ( R =0.277, P =0.00006), Gro-a/CXCL1 ( R =0.211, P =0.0075) and IL-16 ( R =0, 211, P =0.00001). There was a significant negative correlation between cognitive dysfunction and concentrations of Eotaxin-2/CCL24 ( R =–0.378, P =0.00075), Gro-a/CXCL1 ( R =–0.313, P =0.0035), and IP-10/CXCL1 ( R =–0.214, P =0.00023), and between limited activities of daily living (IB) and concentrations of MPIF-1/CCL23 ( R =–0.345, P =0.0024) and Gro-a/CXCL1 ( R =–0.210, P =0.00001). Conclusion. Chemokines form the CC family — MPIF-1/CCL23 and Eotaxin-2/CCL24, and the CXC-Gro-a/CXCL1 and IL-16 clusters are the principal cytokines associated with the dynamics of patient’s motor and cognitive functions recovery in the acute period of ischemic stroke. Although obtained results demonstrate negative effect of increased MPIF-1/CCL23, Gro-a/CXCL1, IL-16 and Eotaxin-2/CCL24 concentrations on the improvement of motor and cognitive impairments, further studies are needed to verify the CXC and CC subfamilies chemokines as prognostic markers of patient’s functional outcome in the acute period of ischemic stroke.

The aim of this study was to assess the value of nitric oxide (NO) and endothelin-1 (ET-1) serum concentrations as potential biomarkers for predicting the functional outcome in patients with acute ischemic stroke. Material and methods. A total of 37 patients diagnosed with ischemic stroke and admitted to a multidisciplinary vascular center were included in the study. The patients were divided into two groups based on the severity of neurological deficits as determined by the National Institutes of Health Stroke Scale (NIHSS): Group 1 consisted of 20 patients with NIHSS scores 15, and Group 2 consisted of 17 patients with NIHSS scores 15. The functional outcome was assessed using the NIHSS absolute values and the degree of disability measured by the Modified Rankin Scale (mRS) by comparing the values before and after baseline treatment. Lab evaluation included quantitative assessment of stable NO and ET-1 metabolites in patient’s serum at admission and on day 10 of hospital stay. The SPSS Statistics V23.0 for Windows software package, Python programming language, and Pandas and SciPy libraries were used for statistical data processing. Results. Group 1 patients demonstrated a statistically significant decrease in NIHSS ( P =0.0013) and mRS ( P 0.0001) scores, which was indicative of a favorable functional outcome. Group 2 patients showed some recovery of only neurological deficit measured by NIHSS scale ( P =0.0012), changes in degree of disability by mRS were statistically insignificant. On Day10 of hospital stay, both groups showed a clinically significant increase in ET-1 content, and slight change in NO concentration. NIHSS score demonstrated a significant negative correlation with baseline ET-1 concentrations: R =–0.82, P =0.00023 — in Group 1; R =–0.55, P =0.00075 — in Group 2. Modified RS scores showed negative correlation with NO ( R =–0.50, P =0.00044) and ET-1 ( R =–1.0, P =0.0074) concentrations in Group 1, and positive correlation with NO ( R =0.55, P =0.0023) and ET-1 ( R =0.33, P =0.04) concentrations in Group 2. Conclusion. Monitoring of NO and ET-1 serum concentrations provides valuable insights for personalized assessment of the anticipated functional outcome in patients with cerebral ischemia. Further research and the development of prognostic mathematical models are needed to validate the use of endothelial function markers as predictive indicators of patients' recovery potential during the acute phase of ischemic stroke.

Better understanding of ischemic brain injury mechanisms is important for the development and improvement of diagnostic and therapeutic modalities for management of ischemic stroke. As experimental studies are on demand, there’s a need for relevant models of focal brain lesions. Photochemically induced thrombosis remains one of the most popular models of ischemic stroke.The purpose of the reviewis to consider the pathogenesis and applicational relevance of the photochemical thrombosis in ischemic stroke modeling.Material and methods.The information was searched using PubMed and Google Scholar databases and keywords «photothrombotic stroke» without language restrictions. 74 papers out of more than 600 sources were found the most relevant for the purpose of this review and selected for the analysis. Of these, more than 50% have been published in the last five years. The criterion for excluding a source was an inconsistency with the objectives of the review and low information content.Results.We outlined a variety of features in modeling photothrombotic stroke, analyzed the advantages and disadvantages of the model, presented data on current method’s modifications, as well as approaches to evaluation of brain lesions in ischemic stroke induced by photothrombosis, and summarized information about the mechanisms of brain damage induced in this model.Conclusion.Several advantages of the photothrombotic stroke model, such as low invasiveness, high reproducibility, inherent control of brain infarction volume and low mortality, determine its active use in experimental studies of ischemic stroke. Pathological processes in the brain modeled by photochemical thrombosis are similar to the processes occurring in acute ischemic cerebral circulation events. Therefore, this model provides insights into cellular and molecular mechanisms of ischemic brain damage, and can be used for developing novel therapeutic approaches for management of ischemic stroke.

Personalized medicine (PM) is a major trend in health care development in the 21st century. This area includes studying risk factors for disease development (prediction), interventions for preventing diseases (prophylaxis), individualization of diagnosis and treatment (personalization), informing the patient on disease prevention and treatment (participation). In the recent years, an intense research to introduce the personalized medicine principles into the management of critically ill patients, has been under way. This includes identification of patient groups based on genomic research, development of diagnostic tests using molecular markers, creation of novel classes of drugs based on individual patient characteristics.The aim of the review is to summarize the available data on the implementation of the principles of PM in the routine practice of critical care institutions.We analyzed more than 300 sources of literature from the Pubmed and Scopus databases, as well as the RSCI database. Eighty five most relevant sources were selected for the review. The paper reports data on the organization and results of implementation of PM principles and advanced technologies, such as Emergency Medicine Sample Bank (EMSB), in the daily activity of clinics providing emergency critical care. The formation of the novel PM concept focused on the treatment of critically ill patients has been discussed. The review contains detailed data on the patterns of development of specific critical illnesses such as acute cerebrovascular events, acute respiratory distress syndrome, traumatic brain injury, shock, myocardial infarction, cardiac rhythm and conduction disturbances. Medication efficacy in view of individual genetic patient characteristics has also been highlighted. No research limitations on the subject were identified.Conclusion. The analysis of literature has demonstrated positive results of implementing PM principles in prevention, diagnosis and treatment of critically ill patients. Creation of Biobanks, development of training programs and regulatory documentation, advancing the scientific research, introduction of new methods of diagnosis and treatment will contribute to the implementation of PM principles in practical healthcare.

The article is devoted to two unique icons commissioned by the Kaluga merchant Mikhail Makarov to commemorate the water pipe with a fountain built with his efforts in Kaluga. The first icon was executed in 1829 and solemnly installed in the City Duma of Kaluga. In 1837, M. Makarov ordered to paint its copy, which was kept in the family of his descendants until 1937. Unfortunately, only the last icon has survived and is now reposited in the State Museum of the History of Religion (St. Petersburg). The iconographic analysis and historical evidence of veneration of the lost original allow establishing the intent of the customer. The composition of the icons has no direct protographs, although some icon pieces influenced its formation (for example, Marian iconography of “Joy of all Who Sorrow” and “The Life-Giving Spring”). The non-typical iconographic idea of the customer forced the icon painter to resort to a set of artistic means unusual for icon painting. On the one hand, the masterpiece demonstrates the traditional methods of Kaluga icon painting of the late Nicholas I Empire era, but on the other hand, the influence of the provincial pictorial primitive is clearly noticeable. The icon executed by the merchant Makarov’s order in 1837 is a unique artwork in terms of its iconographic program and artistic performance. Due to the reliable date of creation and the confirmed Kaluga origin, the icon from the State Museum of the History of Religion occupies an important place in the history of Kaluga icon painting.

The aim of the study is to summarize the histology and morphometry of cortical neurons in acute clozapine and ethanol poisoning. Material and methods . Histological examination of the parietal cortical brain samples of 26 patients died during the Day 1 of acute clozapine and ethanol poisoning (23 males and 3 females aged 22-63 years) was performed. The blood ethanol level was 1.4-4.1%o. The level of clozapine in the blood ranged between 0.24 and 5.8 mg%, in the liver between 0.097 and 6.5 mg%, in kidneys between 0.03 and 3.5 mg%. The cortical samples for morphometric examination were placed in 10% neutral paraformaldehyde, the histological sections were done and stained with hematoxylin and eosin, as well as according to Niessl. The morphological analysis was performed using the video light microscopy. The number of damaged neurons (with separate quantification of reversible, intermediate, and irreversible damage) was assessed. The statistical analysis was done using the non-parametric methods. Results . The signs of brain neuronal damage in acute clozapine and ethanol poisoning, as well as forensic chemical tests, might be used for establishing the direct cause of death.

OBJECTIVEEvaluation of the relationship between the activity of proteolytic enzymes (cathepsin D and calpains) and the dynamics of the fluorescence intensity of the coenzymes nicotinamide adenine dinucleotide (NADH) and flavin adenine dinucleotide (FAD) in the rats' skeletal muscles in relation to the time of death. The proteolytic activity of enzymes in rat skeletal muscle was determined at the postmortem time points corresponding to the most significant changes in the dynamics of coenzymes NADH and FAD fluorescence intensity. The proteolytic enzymes activity was found to be low during the period of increasing intensity of NADH fluorescence observed within 3 hours after death. An increase in the activity of proteolytic enzymes was registered in 4.5 hours after death which corresponds to the initial point of decrease in NADH fluorescence intensity. In 24 hours post-mortem, corresponding to increased FAD fluorescence intensity a significant decrease in the activity of calpains was found. The results of the study suggest that the nature of the postmortem dynamics of the fluorescence intensity of coenzymes is largely due to the peculiarities of intracellular proteolysis. The study results suggest that the pattern of post mortem changes in coenzyme fluorescence intensity is largely attributable to the specifics of intracellular proteolysis. The relationship between coenzyme fluorescence and molecular mechanisms of cell death confirms the viability and feasibility of laser-induced spectroscopy for post-mortem changes assessment when determining the time of death.

The author analyzes the main challenges facing the agri-food complex in accordance with the Strategy of scientific and Technological Development of the Russian Federation and the key challenges formulated by the author. The essence of event-joker is revealed. The system of responses to calls is justified. The article describes the possibilities of increasing the production of organic products, for which Russia has all the initial conditions. The conclusion is made about the prospects for the development of the agri-food complex in the context of keys challenges.

According to epidemiological studies, the leading cause of morbidity, disability and mortality are cerebrovascular diseases, in particular ischemic and hemorrhagic strokes. In recent years considerable attention has been given to the study of molecular markers of ischemic and hemorrhagic strokes. These studies are relevant because brain-specific protein biomarkers of neurons and glial cells can provide valuable and timely diagnostic information necessary for clinical decision-making.The aim of the study was to reveal the differences in the serum level of molecular markers in acute, subacute and early recovery periods of ischemic and hemorrhagic strokes.Material and methods. The study included 59 patients. Twenty patients were diagnosed with hemorrhagic stroke and 39 had ischemic stroke. The control group included 20 volunteers. Serum levels of molecular CNS markers were determined in acute, subacute, and early recovery stages of stroke. The serum levels of CNS molecular markers of patients with ischemic and hemorrhagic stroke was measured quantitatively by enzyme immunoassay. Statistical analysis was performed by nonparametric Mann-Whitney method.Results. The level of brain-derived neurotrophic factor (BDNF) in the control volunteers was 574.5 [455.5; 615] pg/ml. Significant differences were found for acute and subacute periods of hemorrhagic stroke: it was 674 [560; 749] pg/ml (P=0.003) and 664 [616; 762] pg/ml (P=0.0001).The level of neuron-specific enolase was significantly increased in all periods of the study: it was 4.15 [3.53; 4.8] ng/ml in the control group, 5.4 [4.4; 6.4] ng/ml in acute period of ischemic stroke (P<0.001), 5.4 [4.4; 6.4] ng/ml in early recovery period of ischemic stroke (P=0.001), 5.1 [4.6; 6.4] ng/ml in acute period of hemorrhagic stroke (P=0.014), 664 [616; 762] ng/ml in subacute period of hemorrhagic stroke (P=0.003).In the control group, the serum S-100 protein level was 4.5 [3.8; 5.4] ng/ml. In the acute and early recovery periods of ischemic stroke, S-100 protein level has significantly fallen down to 4.1 [3.4; 4.6] ng/ml (P<0.031) and 3.9 [3.4; 6] ng/ml (P=0.014), respectively. Glial-cell derived neurotrophic factor level was 1.98 [1.64; 2.1] ng/ml in the controls and increased up to 2.4 [2.2; 5] ng/ml (P=0.002) in the acute period and 2.4 [2.3; 2.6] ng/ml (P<0.001) in the subacute period of hemorrhagic stroke.The vascular endothelial growth factor receptor-1 (VEGFR-1) was significantly lower in the subacute period of hemorrhagic stroke: 485 [211; 945] pg/ml in the subacute period vs 903.5 [626; 1115] pg/ml in the controls (P=0.001).Conclusion. We found differences in the serum level of molecular markers in patients with ischemic and hemorrhagic strokes. In the acute period, early recovery period of ischemic stroke, and subacute period of hemorrhagic stroke, there was an increase in the serum level of neuron-specific enolase. The level of brain-derived neurotrophic factor increased significantly in the acute and subacute periods of hemorrhagic stroke. In the acute and early recovery periods of ischemic stroke, the level of S-100 protein decreased. The level of glial cell-derived neurotrophic factor increased in the acute and subacute periods of hemorrhagic stroke. In the subacute period of hemorrhagic stroke, the level of endothelial growth factor receptor-1 significantly decreased. Moreover, there was significant difference between values of this parameter in the subacute period of hemorrhagic stroke and in the early recovery period of ischemic stroke.

The aim of the study: to assess the lung histopathology in acute intoxication with baclofen alone and its combination with alcohol (in the same dose) 3 hours after the ingestion.Materials and methods. The study was performed on 15 male Wistar rats weighing 290-350 g and aged 20 weeks. The animals were divided into 3 groups, 5 animals each: control group that included intact rats; Group 1 composed of rats received baclofen alone; Group 2 that included rats received a combination of baclofen and ethanol. Baclofen was administered orally at a dose of 85 mg/kg animal weight under anesthesia (chloralose), and 40% ethanol, 7 ml/kg animal weight, was orally administered along with baclofen at the same dose. Animals of all groups were sacrificed after 3 hours by overdosing anesthetic agent. Lung tissue samples were examined by light microscopy using a video system at x400 magnification. The following histological characteristics were evaluated: circulatory disorders (engorged capillaries and venules, hemorrhages in interalveolar septa and alveoli, sludge), atelectasis (including partial), emphysema, cellular response (increased WBCs in the interalveolar septal area), thickening of interalveolar septa due to edema, epithelial desquamation into bronchial lumen. The diameter of alveoli and thickness of interalveolar septa were measured.Results. Three hours after the baclofen administration, circulatory disorders in the lungs (engorged venules and capillaries, hemorrhages in the interalveolar septa, sludge), emphysema, atelectasis (complete and partial) as well as cellular response (leucocyte infiltration of interalveolar septa) were detected. In the Group 2, baclofen resulted in circulatory disorders (engorged venules and capillaries, sludge), emphysema, atelectasis (complete and incomplete), cellular response (infiltration with leukocytes), as well as fluid in the lumen of bronchioles. In Group 1, the alveolar diameter was significantly larger than in the control group and Group 2, while the thickness of the interalveolar septa was lower. In group 2, alveolar diameter was significantly less than in group 1, but still greater than in the control group. The thickness of the interalveolar septa in group 2 was significantly greater than in the control group and group 1.Conclusion. After administration of baclofen alone and in combination with ethanol, the following alterations were found in the lungs: circulation disorders (venular and capillary engorgement, sludge), increased vascular permeability because of developing hypoxia, leukocyte infiltration of interalveolar septa. The monitoring of morphological alterations may aid in evaluating the severity of pathological processes in intoxication with baclofen alone and in combination with ethanol and in determining the method of intoxication (baclofen alone or in combination with ethanol).

Values of the standard enthalpies of formation D,L-alanyl-D,L-serine are calculated using additive groups approach based on group systematics with such classifications of fragments as the Benson classification, which considers the effect of the primary environment of atoms. The heat effects of the dissolution of crystalline D,L-alanyl-D,L-serine in water and in solutions of potassium hydroxide at 298.15 K are determined via direct calorimetry in a wide range of concentrations. The standard enthalpies of formation of the peptide and products of its dissociation in an aqueous solution are calculated.

The aim of the study was to identify the pathomorphology of brain damage in patients who died of COVID-19.Material and methods. Autopsy reports and autopsy brain material of 17 deceased patients with pre-mortem confirmed COVID-19 infection were analyzed. Fatal cases in which COVID19 was the major cause of death were included in the study. Five people were diagnosed with cerebral infarction. Organ samples were taken for histological examination during autopsy. Sections were stained with hematoxylin and eosin and by Nissl to assess brain histopathology. To study the vascular basal membranes the PAS reaction was used, to detect fibrin in vessels phosphotungstic acid-hematoxylin (PTAH) staining was used, to determine DNA in nuclei sections were stained according to Feulgen, to detect RNA in neuronal nuclei and cytoplasm sections were stained with methyl green-pyronin. Immunohistochemical study of a neuronal marker, nuclear protein NeuN, was performed to assess neuronal damage.Results. The signs of neuronal damage found in patients who died of COVID-19 included nonspecific changes of nerve cells (acute swelling, retrograde degeneration, karyolysis and cytolysis, ‘ghost' cells, neuronophagia and satellitosis) and signs of circulatory disorders (perivascular and pericellular edema, diapedesis, congested and engorged microvasculature).Conclusion. Brain histopathological data indicate damage to the central nervous system in COVID-19 patients. Ischemic stroke in patients with COVID-19 is mostly caused by a combination of hypoxia resulting from respiratory failure and individual risk factors, including cerebrovascular atherosclerosis and hypertension.

The aim of the study is to summarize the histology and morphometry of cortical neurons in acute clozapine and ethanol poisoning.Material and methods. Histological examination of the parietal cortical brain samples of 26 patients died during the Day 1 of acute clozapine and ethanol poisoning (23 males and 3 females aged 22-63 years) was performed. The blood ethanol level was 1.4-4.1%o. The level of clozapine in the blood ranged between 0.24 and 5.8 mg%, in the liver between 0.097 and 6.5 mg%, in kidneys between 0.03 and 3.5 mg%. The cortical samples for morphometric examination were placed in 10% neutral paraformaldehyde, the histological sections were done and stained with hematoxylin and eosin, as well as according to Niessl. The morphological analysis was performed using the video light microscopy. The number of damaged neurons (with separate quantification of reversible, intermediate, and irreversible damage) was assessed. The statistical analysis was done using the non-parametric methods.Results. The signs of brain neuronal damage in acute clozapine and ethanol poisoning, as well as forensic chemical tests, might be used for establishing the direct cause of death.

The study aims to identify functional and metabolic disorders of the heart that occur under the influence of toxic doses of baclofen. Material and methods. Two series of vivisections were carried out on male Wistar rats weighing 200–300 g. Animals of the control series were injected with a 0.9 % sodium chloride solution into the stomach through a tube at the rate of 6 ml/kg of body weight. In the trial series, rats were injected into the stomach with baclofen in saline sodium chloride solution at a dose of 145 mg/kg body weight. General inhalation anesthesia was performed with sevoflurane 4 vol. % with an oxygen flow of 2 l/min in an induction chamber. The animals were fixated on their backs on the operating table. Spontaneous breathing was carried out through the mask of the anesthetic machine. The electrocardiogram, heart rate (min-1), respiratory rate (min-1) were recorded, and blood pressure was invasively measured with a BP-100 device. Arterial blood samples were taken for biochemical studies. Euthanasia was performed by intra-arterial injection of a 2 % solution of lidocaine under general anesthesia with chloral hydrate, and then pieces of the myocardium were taken for morphological examination. Results. It was found that baclofen in toxic doses disrupts the function of automatism and conduction, causes bradypnea. Morphologically, microcirculation disorders in the form of plasma separation, stasis, sludge and micro thrombosis, perivascular edema and hemorrhages, as well as cardiomyocytes damage (their wavy deformation and nuclear hyperchromatism) were revealed in the heart muscle.

The incidence of ischemic stroke remains high in many countries, despite a declining trend in the incidence of brain circulation disorders. Limited knowledge of the pathogenesis, diagnosis, clinical presentation, and treatment of this life-threatening disease can be complemented by modelling of ischemic stroke on animals, particularly, in rodents (rats, mice). The aim of review : to provide a rationale for choosing an optimal model of human ischemic stroke. Among more than 300 primary literature sources from various databases (Scopus, Web of science, RSCI, etc.), 84 sources were selected for evaluation, of which 72 were published in the recent years (2015–2019). The criteria for exclusion of sources were low relevance and outdated data. The review examined six experimental models of acute cerebrovascular events including middle cerebral artery occlusion, embolic stroke model; phototrombosis; models using thrombin, endothelin-1 and electrocoagulation of the middle cerebral artery. The review outlines the factors influencing reliability and reproducibility of research results, related to adherence to the rules of animal accommodation and acclimatization, nutrition and care, selection of anesthesia and pain relief methods, compliance with aseptic techniques, monitoring of basic physiological parameters at all stages of the ischemic stroke modeling experiment, with humane withdrawal of animals from the experiment. It was concluded that the model of ischemic stroke, based on the occlusion of the middle cerebral artery, is most promising as being the closest to features of human ischemic stroke and enabling to obtain reproducible results in the experiment.

Aim of the study is to identify patterns of variations of the fluorescence intensity of NADH (reduced nicotinamide adenine dinucleotide) and FAD (oxidized flavin adenine dinucleotide) in the skeletal muscle depending on the time since death. For the evaluation of fluorescence intensity of the studied coenzymes, laser-induced spectroscopy in situ was used. We revealed the dynamic of the fluorescence intensity of NADH and FAD in the skeletal muscle of a rat at different times during the post-mortem period, and theoretically justified the observed phenomena. The results obtained allow us to consider the studied indicators as a potential criterion for determining the post-mortem interval.

The enthalpies of complexation of the Sm 3+ and Ce 3+ ions with L-leucine at 298.15 K and an ionic strength of 0.5 (KNO 3 ) have been determined by the calorimetric method. The thermodynamic characteristics of complexation of lanthanide ions with amino acids have been calculated. The potentiometric method was used to determine the stability constants of cerium and samarium complexes with the L-leucinate ion at 298.15 K and an ionic strength of 0.5 (KNO 3 ).