Archive

Purpose of the study: substantiation of indications and assessment of results X-ray endovascular treatment of "critical" PE in patients with acute hemorrhagic cerebrovascular accident. Material and methods: the study included 47 patients with acute violation of cerebral circulation for hemorrhagic and mixed types complicated by massive pulmonary thromboembolism of high risk, with "critical" manifestations of right ventricular failure. Depending on the method of PE treatment used, the patients were divided into 2 groups: the study group (17 people), in which endovascular mechanical fragmentation of thromboembols was performed, and the control group (30 people), in which only basic intensive therapy was used. Results: patients of the study group underwent thromboembolic fragmentation in order to transfer embolism of the trunk and the main branches into embolism of smaller branches of the pulmonary artery. Technical success of the procedure (destruction of the central thromboembolus) was achieved in 100% of the cases. 14 patients (82.4%) showed positive clinical dynamics in the form of an improvement in the general condition, a decrease in pressure in the pulmonary artery, and a decrease in the volume of the lesion of the pulmonary bed according to CT angiography. Three patients (17.6%) died in the early postoperative period. In the control group of 30 patients, 25 patients died, hospital mortality was 83.3%. Conclusion: the method of catheter endovascular fragmentation of thrombi for the treatment of "critical" pulmonary embolism in patients with acute hemorrhagic cerebrovascular accident leads to a rapid and safe decrease in pulmonary artery pressure. 

The actuality of the problem of thermal trauma is determined by its high prevalence. Severe disorders of central, regional and peripheral hemodynamics are developing with a predominant violation of microcirculation and metabolic processes in the body during burn disease. Promising NO donors suitable for biomedical use are dinitrosyl iron complexes (DNIC). The aim of the study was to evaluate the effect of DNIC on the state of microcirculation in normal conditions and on the model of combined thermal trauma (CTT). The experiments were carried out on white male rats of the Wistar line. CTT (contact burn on the area of 20% of the body surface and thermal inhalation exposure to hot air and combustion products for 20-30 seconds) was applied under anesthesia. Animals with CTT were treated daily with intraperitoneal injections of a 10% DNIC solution (1 ml; 0.3 micromol/l). Laser Doppler flowmetry was used to assess the dynamics of the microcirculation state. The physiological and biochemical mechanisms of microcirculation disorders in CTT are revealed in the work. There was an increase in the endothelial, neurogenic and respiratory components of microcirculation, microhemodynamics of the border area of the burn, and the index of the microcirculation bypass. It was shown that when using 0.3 micromol/l of DNIC in rats under normal conditions, there is a decrease in the neurogenic and respiratory components, an increase in perfusion and the myogenic component of the microcirculatory channel. The role of 0.3 micromol/l of DNIC in the normalization of microcirculation in CTT was established.

The work aimed to study the protein spectrum, morpho-functional state of erythrocyte membranes under stress and correction by low-intensity laser radiation. The experiments were carried out in vitro. Low-intensity laser radiation with a wavelength of 830 nm and a power of 90 mw was used for irradiation. Laser therapy was performed using an autonomous laser shower "MarsIK" (NPO "Petrolaser", St. Petersburg). The protein fractions of red blood cells were analyzed by electrophoresis, the morphology of red blood cells by laser interference microscopy, the еletrophoretic mobility of erythrocytes was measured by microelectrophoresis in our modification and the concentration of malondialdehyde in red blood cells by reaction with thiobarbituric acid spectrophotometrically. It is proved that the change of protein fractions in the erythrocyte membrane under stress, a decrease in the amount of spectrin, band 3 protein, glycophorin and ankirin. The stress is characterized by an increase in the number of echinocytes, stomatocytes and degenerative-altered red blood cells. Exposure to LLLT on blood samples determined the recovery of the studied parameters to the control group values (physiological norm). The role of the discovered metabolic changes in RBC in stress and their correction by LLLT is under discussion.

Increase in the life expectancy of the population is associated with a tendency of aging in patients with chronic heart failure (CHF). Gender, age and genetic differences of the individual risk factors are still discussed in the aspect of influence on the heart failure clinical phenotype. The study aimed to identify the gender and age differences of chronic heart failure clinical characteristics in terms of the ZBTB17 gene (rs10927875) polymorphism. Materials and methods. A total of 351 patients with CHF of ischemic etiology of both genders were examined. The average age of men was 65.3±9.9, women  ̶  69.7±9.61 years. Results and conclusions: CHF of ischemic etiology in the absence of differences in the burdened family history, previous myocardial infarction (MI) observed mainly in middle-aged and elderly men and elderly and senile women. Significant gender differences in comorbidities were revealed: in 40% of men, CHF was associated with chronic obstructive pulmonary disease (COPD), in 47.3% of women ‒ with chronic kidney disease (CKD) and in 32.2% - with diabetes mellitus (DM). The distribution of rs10927875 polymorphism ZBTB17 genotypes were corresponded to the Hardy-Weinberg equilibrium (χ2 = 0.272, p = 0.873). CC genotype in men was associated with reduced left ventricular ejection fraction (LVEF). CT genotype in women associated with CHF FC III and IV due to the frequent indications in the past on myocardial infarction, concomitant DM, obesity and hypercholesterolemia. The CT genotype rs10927875 was characterized by a frequent combination of CHF with COPD in men and CKD and DM in women.

The aim of the work was to study the effects of photobiomodulation (PBM) in the red spectrum (640 nm) with fluences from 3 mJ/cm² to 2 J/cm² in combination with ionizing radiation (IR) at doses of 2-6 Gy against human BJ-5ta-hTERT - postnatal fibroblasts. The cells were exposed to low-intensity red light before or after their exposure to IR, the viability of the cells was determined by MTT 24 hours after the last exposure. It is shown that the effects of PBM depend on the fluence of PBM, the dose of IR and the sequence of the actions of these physical factors on cells. The adaptive effect of PBM was observed only for high fluences-1 and 2 J/cm² when exposed to PBM and subsequent (after 1 hour) irradiation of IR. At the same time, the stimulating effect of PBM was observed only for low fluences from 3 to 300 mJ/cm² under IR irradiation and subsequent (after 1 hour) exposure to PBM. These data should be taken into account when using PBM for the correction of adverse events of radiation therapy in an oncological clinic.

In probabilistic conditions, people choose low-payoff alternatives on some trials, thus failing to maximize their payoffs. We suggest that such behavior implicates exploration of task rules by choosing risky options instead of exploiting more rewarding alternatives. We hypothesized that exploration would affect brain responses to feedback. Further, a shift to exploration develops gradually and, therefore, a decision to make an exploratory choice may be observed on trials preceding risky choices. We investigated beta power (16–30 Hz) in the magnetoencephalographic data from 62 healthy participants performing a two-choice probabilistic gambling with monetary gains and losses. The effects were found at 600–800 ms after feedback onset in frontal, central and occipital brain regions. On trials preceding risky choices we identified a decrease in beta power which implies a change in decision-making strategy and a shift towards cognitive flexibility and exploration. An increase in beta power during risky decisions indicates that reward learning mechanisms are implicated. Increases in beta power following losses in risky choices indicates at the process of updating the internal representation of the task. In summary, current findings reveal that the outcomes of exploratory trials are processed differentially, while there is no evidence of such processing on exploitatory trials. This corroborates the hypothesis that exploratory choices represent active probing into the surmised task rules. Current findings also suggest that the processing of outcomes preceding the exploratory trials is altered in such a way that subjects override their intention to use the utility model and reset their behavioral strategy.

Cognitive status and EEG in the theta, alpha, and beta ranges were studied using cluster analysis by discrete optimization in patients with cardiovascular disease in the preoperative period of coronary artery bypass grafting. The cognitive status was measured by Mini-Mental State Examination (MMSE) scale, and an integral indicator of cognitive status (IICS) formed on the basis of complex testing the indices of visual-motor responses, attention, and memory. The new method of clustering the EEG power and the cognitive status made it possible to distinguish groups of patients differenced by cognitive reserves. The IICS better differentiates groups than MMSE. The factors of age and education were decisive only in specific groups. The clusters characterized by the most represented cognitive reserves according to the higher both MMSE and IICS indicators included less pronounced activation of the cortex according to more power of the theta, alpha, and less beta rhythm. Patients with supposedly minimal reserves are differed by a low level of cognitive status, as well as education level together with higher activation state of the cortex. The third type of clusters was distinguished by an unstable composition due to the variability of EEG indicators in it, mostly cortical activity at the alpha1 frequencies. The EEG neurophysiological approach, together with cognitive screening and proposed clustering analysis, could be helpful in understanding mechanisms of cognitive reserves and identify the risk factors of postoperative cognitive dysfunction in patients with brain cardiovascular damage.

The extracellular matrix plays an important role in brain function. Recent findings suggest that disruption of hyaluronan-based extracellular matrix can cause seizure-like activity (Vedunova et al., 2013). Epilepsy can be characterized by an excessive influx of Ca2+ ions through (Ca2+) – permeable AMPA receptors, which may, in certain circumstances, contribute to seizures. Ca2+ – permeability of these receptors is dependent on RNA-editing of pre-mRNA transcript of GluA2 subunit at the Q/R site. Regulation of this process is carried out by a special nuclear enzyme, ADAR2 (Adenosine Deaminase Acting on RNA-2). Thus, the study of the principle of operation of this enzyme can contribute to understanding the mechanism of epileptogenesis.

Emotion regulation is a popular research topic in social, clinical, cognitive psychology, and neurophysiology. Event-related potentials (ERPs) studies have high temporal resolution and are therefore conventionally used in emotion research to study the patterns of emotion processing. Advances in digital technologies are promoting neuro-psychological research of emotion and attention in virtual reality (VR). In this work, for the first time, we investigated how the presented emotional facial expressions in VR modulate ERP components in conditions of different combinations of passive or active attention and random or linear presentation sequence. We found the higher amplitude of the C1, N170, P2, P3, P4 ERP components in the condition of active attention compared to passive attention during the random presentation of emotional 3D facial expression. During the linear presentation of emotional 3D facial expressions, a statistically significant difference was found only for the C1 ERP component in conditions of both passive and active attention. We proved that the P2 ERP component represents the perception of positive and negative 3D facial expressions encoding the emotional valence of the stimuli. We also found no statistically significant difference in latency of ERP components between passive and active attention to emotional 3D facial expressions.

The study aimed to evaluate the effectiveness of previously developed methods of adaptive neurostimulation in correcting stress-induced states in specialists who demonstrate signs of post-traumatic stress disorder (PTSD) and professional burnout syndrome (PBS). Materials and methods. Each of the 17 stressed subjects participated in three examinations, alternated in random order. In the control experiment (control), simple listening to classical music was used. In two other examinations, musical or light-musical stimulation was used, automatically modulated by feedback signals from the rhythmic components of the subject's electroencephalogram (EEG). In the first case (musical feedback), the subjects were presented with music-like stimuli formed on the basis of the subject's alpha EEG oscillator. In the second case (double feedback), such musical stimulation was supplemented by rhythmic light stimuli generated by online transformations of the native EEG of the subject. Results. Comparison of the effects of both experimental conditions with the control one allowed us to establish that only in the presence of feedback from the EEG, there is a significant increase in the power of alpha EEG rhythm, accompanied by positive emotional reactions, a decrease in the level of disadaptation and stress, as well as a significant increase in the assessments of health and mood of the subjects. The most pronounced psychophysiological effects were recorded under light-music stimulation with double feedback from the EEG. Conclusion. The obtained results make it possible to suggest the described methods of adaptive neurostimulation as a means of psychotherapeutic correction of PTSD and PBS, especially during the COVID-19 pandemic.

The three-dimensional structure of tumor tissue and particularly cell-cell and cell-extracellular matrix adhesion is an important factor that can determine the phenotype of tumor cells. In this work, we have investigated the abundance profile of actin-binding adhesion proteins in human ovarian adenocarcinoma cell lines SKOV-3 and SKOV-3.ip. We have investigated levels of total and superficially localized adherens junctions proteins E- and N-cadherin, gap junction protein сonnexin-43 and cell-extracellular matrix contacting integrin beta-1. Our results indicate a complete absence of epithelial marker E-cadherin, a low level of mesenchymal N-cadherin and high levels of connexin-43 and integrin beta-1. Modest superficial localization of the represented proteins was observed, indicating their mislocalization. SKOV-3 cell line was characterized by higher levels of the total content of studied cell-cell contacts proteins and a lower level of superficially localized integrin beta-1, which is both considered to be associated with lower tumor aggressiveness. The revealed differences in the profile of adhesion proteins are in line with the accepted view on SKOV-3.ip cell line having a more aggressive phenotype than that of SKOV-3. The revealed features of the total abundance of the adhesion proteins and their superficially localized pool made it possible to supplement the information on the nature of phenotypic differences between the studied cell lines.

Type 2 diabetes mellitus (T2D) is one of the most common endocrine diseases in the world. It is characterized by dysfunction of pancreatic β-cells, insulin resistance, and hyperglycemia. Despite numerous studies on the pathogenesis and risk factors of diabetes, there is still no consensus on how best to diagnose, classify, and treat the disease. Accumulating evidence suggests that antidiabetic drugs can course unwanted side effects. S-15176 difumarate salt, a novel derivative of trimetazidine, inhibits the rate-limiting enzyme of fatty acid β-oxidation carnitine palmitoyltransferase I and has anti-ischemic properties, which makes it useful as an antidiabetic agent. Here, the effect of chronic treatment with S-15176 difumarate salt on the leukocyte formula and cytochemical indices of the peripheral blood neutrophils (myeloperoxidase activity, free phospholipids, and lysosomal cationic proteins) of C57Bl/6 mice in control and experimental T2D was studied. It was found that in the control group, S-15176 difumarate salt decreased the number of neutrophils containing lysosomal cationic proteins and the cytochemical coefficient of the cells. The treatment of diabetic mice with S-15176 had no significant effect on the activity of myeloperoxidase and free phospholipids in neutrophils. The results obtained suggest that the use of S-15176 difumarate salt as an antidiabetic drug does not induce changes in peripheral blood markers associated with immune-related adverse effects.

We have explored the features of PPARγ2 gene alleles expression in elderly patients with comorbid conditions such as obesity and coronary artery disease. 140 patients of both sexes (54.3% men and 45.7% women) aged 60-89 were examined. The main group included 70 pts with CHD; the control group included 70 pts without CHD. Pro12 allele carrier state in the main group was 85%, and Ala12 allele carrier state – 15%. Pro12Ala and Ala12Ala genotypes, Ala12 allele were detected more often in patients with coronary artery disease than in the control group (p = 0.0008 and p = 0.0003, respectively). Pro12Ala genotypes (OR = 2.02, CI = 1.28–3.19, p = 0.003) and Ala12Ala (OR = 2.002, CI = 1.32–3.04, p = 0.0006) of Ala12 gene PPARγ2 carrier state increases the risk of CHD developing by 2 times. It was confirmed that nuclear PPARs are capable of controlling development, differentiation, metabolic homeostasis and reproduction. The role of various genotypes of the PPARγ2 gene in the regulation of lipid metabolism and angiogenesis in comorbid conditions in elderly patients may help to identify new methods of their treatment.

CuO in the form of micro- and nano-sized colloidal particles enters the human body from environment. The aim of the study is the identification of morphological changes in rat liver tissues during chronic oral intake of micro- and nanosized CuO by image analysis. The experiments were performed on 45 male Wistar rats (3 groups: experimental (nanosized CuO); comparison (micro-sized CuO); control (water without CuO)). Suspensions CuO were administered to the rats orally once a day. Quantitative morphological parameters were determined by pathomorphological examination and image analysis using the method of constructing Voronoi diagrams (the ratio of cells of various shapes); average cell area; the average size of the cell perimeter and the number of cells per unit area. As a result of the analysis by the constructing Voronoi diagrams, was found that the main part of the model cells corresponding to hepatocytes has the shape of a hexagon. In the control group, their share is 35.89%, in the experience group – 29.09%, and in the comparison group – 30.59%. The density of cells’ distribution in the comparison group is 7 times higher than in the control group; in the experimental group the same indicator is 4 times higher than in the control group. Collectively, the characteristics of morphological changes in liver tissue indicate greater toxicity of nano-sized copper oxide compared to its micro-sized analogue.

Achieving both deep penetration of photons into biological tissue and highly sensitive recording of optical probes' response are the key goals of non-invasive optical imaging. In comparison with the traditional fluorescence imaging in the visible (400–700 nm) and near-infrared (700–900 nm) regions, optical fluorescence imaging in the second optical tissue transparency window (1000–2300 nm) demonstrates low photon scattering, deeper penetration into the tissues and lower autofluorescence. In the present study, biocompatible upconversion nanoparticles with different contents of doping lanthanides, capable of luminescence in the visible and short-wave IR regions, were obtained and characterized. Also, targeted complexes based on Gd-containing nanophosphors were obtained as potential contrast agents for magnetic resonance imaging. Selective binding of targeted complexes to the surface of tumor cells expressing the HER2 receptor was shown.

Methylation of DNA cytosine bases is a key epigenetic modification that plays an important role in the regulation of gene expression and the formation of the epigenome. Numerous studies of the human genome show that there is a close relationship between DNA methylation, age and sex of a person. Until now, the popular model has been the linear change in the methylation level with age. Here we find a fundamentally different DNA methylation behavior, namely the nonlinear dependence of the methylation level on age. We identify CpG probes whose methylation changes exponentially with age or according to a power law, and perform Gene Ontology enrichment analysis of the latter. Our results are relevant to understanding how DNA methylation changes with age and the found nonlinear CpG sites can be used to construct new epigenetic clocks.

Decellularized matrices of animal organs can serve as a promising platform for creating highly relevant threedimensional in vitro models of tumor growth. In this work, the applicability of two decellularization protocols for obtaining the extracellular matrices of various murine organs was examined. The resulting decellularized matrices were characterized by visual integrity and preservation of the tissue architectonics. A high degree of the cellular component elimination was demonstrated while maintaining the basic structures of the extracellular matrix. From the point of view of convenience and ease of use, as well as the quality of the obtained matrices, the method based on the use of detergent sodium dodecyl sulfate and trypsin-aprotinin complex has demonstrated the greatest suitability. In the future, the developed protocol will be used to study tumor-matrix interaction and tissue-specific characteristics of growth and morphology of tumor cells.

The development of clinical forms of infection and endoscopic changes in the gastric mucosa depends on the H.pylori genetic diversity in a given region. The aim of this work was to study the relationship of the genetic profile of H.pylori pathogenicity factors with clinical and endoscopic features of Helicobacter-associated gastritis in Nizhny Novgorod. A number of H.pylori pathogenicity genes of DNA isolates obtained by endoscopy from 151 patients with chronic H.pylori-associated gastritis (non-destructive, erosive, and atrophic) were studied by PCR. Results. In destructive processes in the gastric mucosa, the detection frequency of cagA, vacA s1 m1 genes and a combination of several pathogenicity factors, including iceA A1 and babA was higher than in other forms of gastritis. Atrophic gastritis is characterized by the genetic profile cagA and vacA s2 m2. Infection with several H.pylori strains is determined more often in erosive gastritis and atrophy of the gastric mucosa. Conclusions. In chronic gastritis in Nizhny Novgorod, a predominantly "European" character of the pathogen population structure was revealed - with a moderate content of the most pathogenic cagA, vacA s1-positive strains. Colonization of the gastric mucosa by H.pylori with a genetic structure containing pathogenicity factors cagA, vacA, babA, ice A2, in chronic H.pylori-associated diseases, it is a factor in increasing the severity, activity and prevalence of the inflammatory process, the appearance of signs of atrophy of the gastric mucosa. The greatest influence on these indicators is exerted by the presence of cagA and vacA s1 in the microorganism genome, as well as a combination of several pathogenicity factors.

The features of ischemic brain injury outcome in C57BL/6 mice depending on the right or left common carotid artery occlusion are characterized. The right-hemispheric focal ischemia decreases the body weight, causes spatial memory impairment, and activates the development of a pronounced long-term neurological deficit characterized by ipsilateral limb paralysis, ptosis and muscle dystrophy, which is accompanied by perivascular brain tissue edema. In the left-hemispheric focal ischemia, the neurological status impairments are also observed, but they less pronounced than in case of right-hemispheric ischemia. Moreover, preference to study novelty is reduced, and long-term emotional strain is revealed. The peculiarity of ischemic injury using the left common carotid artery occlusion is accompanied by the presence of hemorrhages and dilated capillaries in the damaged brain hemisphere.