Stimulated contraction of the diaphragm by non-invasive electrical stimulation of the phrenic nerve is demonstrated. A specialized device including a programmable current source and an electrode system has been developed to generate the stimulating signal. We report here a study on the effectiveness of stimulation on the contractile activity of the diaphragm by assessment of transdiaphragmatic pressure.

Results obtained from studies of the development of a device for non-invasive electrical stimulation of the phrenic nerve are presented. A block diagram of the device and schematics of key functional blocks are presented and the design of the device and the original software for its operation are described.

Chronic thromboembolic pulmonary hypertension (CTEPH) is a complication of pulmonary embolism, characterized by high blood pressure in the pulmonary artery combined with impaired lysis of fibrin clots. Previously, the presence of aseptic inflammation in CTEPH was found in the wall of the pulmonary artery branches, as well as perivascularly. However, the role of this inflammation in shaping CTEPH is unknown. The aim of the work was to study the effect of aseptic inflammation on CTEPH formation and progression. The experiments were carried out on male Wistar rats (n = 54). The CTEPH model was reproduced by repeated intravenous administration of partially biodegradable microspheres (MS). Immediately after the last MS administration, all animals were randomly allocated into four groups: (1) control (c.CTEPH) group—physiological saline was administered intramuscularly (i.m.) for 6 weeks; (2) low-dose prednisolone (LDP) group—prednisolone was administered i.m. at a dose of 1.5 mg/kg; (3) high-dose prednisolone (HDP) group—prednisolone was administered i.m. at a dose of 6 mg/kg; (4) healthy or intact (INT) group. After 6 weeks, there were performed the treadmill test, transthoracic echocardiography, cardiac catheterization with blood pressure manometry, and lung tissue histological examination. In a separate series of experiments, the degree of vascular wall and perivascular space inflammatory infiltration was assessed immunohistochemically. In LDP group, the vascular wall hypertrophy index (HI) and the percentage of collagen fibers in the vascular wall were reduced compared to the control group, with the HI being reduced significantly greater than in HDP group. In the latter, there was revealed a positive effect of high-dose prednisolone on the percentage of collagen fibers in the vascular wall, with this parameter being non-significantly different from that in intact animals. By immunohistochemical data, low-dose prednisolone effectively suppressed inflammatory infiltration of the vascular wall and perivascular space. Thus, we revealed the ability of low-dose prednisolone to reduce the degree of remodeling of the pulmonary artery branches by suppressing aseptic inflammation.

This study examines the impact of digitalization on the formation and development of the regulatory subsystem, which is a key component of the human psyche. The findings reveal that digitalization has a significant and complex influence on this subsystem, operating at two complementary levels: analytical and structural. The analytical level reflects a profound decrease in the development of the subsystem's individual components, including essential regulatory processes and their associated qualities. This decline raises concerns about the capacity of individuals to effectively manage their cognitive and emotional resources in a digital context. In contrast, the structural level involves meaningful transformations in the organization, structuring, and integration of these components. These changes indicate a shift in how the regulatory subsystem operates, suggesting that digitalization is reshaping the very foundation of psychological regulation. As a result of this complex influence, a new phenomenon emerges, referred to as the syndrome of reduced personality regulation. This syndrome holds significant implications for overall personality development and regulatory potential, sharing similarities with previously identified syndromes of decreased cognition and metacognition. The structural transformations in the regulatory subsystem, influenced by digitalization, primarily manifest as changes in the degree of organization and integration, rather than qualitative alterations. The qualitative aspects remain invariant and resist the pervasive effects of digitalization, suggesting the subsystem's resilience that may offer avenues for further exploration and intervention.

Ischemic stroke is one of the leading causes of disability and mortality. The key approaches to the treatment of this pathology are thrombolytic therapy and thromboaspiration. Despite their proven efficacy, the application of these methods is limited by a relatively narrow therapeutic window. There remains a great relevance in the further study of the molecular mechanisms of ischemic- reperfusion brain damage within the framework of the ischemic cascade concept. The impact on the mechanisms of induction and implementation of various types of programmed cell death with the help of pharmacological agents is a promising approach to reduce brain damage in ischemic stroke. This review considers the key processes leading to irreversible damage to neurons and their death. The mechanisms of formation and the role of excitotoxicity, calcium overload, oxidative and nitrosyl stress, mitochondrial dysfunction, as well as the triggering of signaling pathways of apoptosis and aseptic inflammation are considered in detail. The issue of various variants of cell death against the background of these pathological processes is discussed. Along with the consideration of signaling pathways that contribute to the progression of brain damage, special attention is paid to the activation of protective signaling mechanisms during ischemia, which provide an increase in cell resistance to death.

The metabolic needs of the brain largely depend on the intensity of the functioning of its various departments, which requires constant regulation of the level of local blood flow. The importance of accurate and timely regulation of cerebral blood flow is enhanced by the lack of substrate stores for autonomous energy production in nervous tissue. In this case, the state of systemic hemodynamics can have a significant effect on organ blood flow. At the same time, given the significant importance of the central nervous system in providing all physiological processes, the regulation of organ cerebral blood flow is aimed at minimizing the possible adverse consequences of the influence of disorders of systemic hemodynamics. In this regard, the regulation of cerebral blood flow is based on multiple and complex physiological mechanisms at various levels. The basic level of regulation of cerebral blood flow is myogenic response, which provides the phenomenon of autoregulation of blood flow in the brain. The review focuses on the physiological mechanisms underlying myogenic regulation as well as the change in this regulation in various diseases.

Ethnopharmacological relevance: Ziziphora clinopodioides subsp. bungeana (Juz.) Rech.f. is a subshrub that is widely distributed in China, Kazakhstan, Kyrgyzstan, Mongolia, Russia, Tajikistan, Turkmenistan, and Uzbekistan. The species is used in traditional medicine for the relief of symptoms connected to cardiovascular diseases like coronary heart disease or hypertension. Aim of the study: was to validate traditional use of Z. clinopodioides subsp. bungeana for the treatment of coronary hearth diseases using in vivo models and to find active compounds responsible for the activity. Materials and methods: Multiple extracts were obtained from the aerial parts of Z. clinopodioides subsp. bungeana using maceration, liquid-liquid extraction, CO2 extraction and ultrasound-assisted extraction. Preliminary screening studies for the evaluation of the efficacy of Z. clinopodioides subsp. bungeana extracts on the model of hemic hypoxia were performed. The most effective samples were selected and included in the main study. Stage 2 of the study evaluated the cardiotropic activity of the selected extracts on a model of chronic heart failure. Preparations were administered to animals intragastrically once a day for 28 days. For the isolation of individual compounds plant material was extracted with 96% ethanol. The obtained crude extract was sequentially extracted with n-hexane and dichloromethane and separated by chromatography on a Diaion HP-20 column. The obtained fractions were further subjected to Sephadex LH-20 column chromatography and eluted isocratically with 96% ethanol (EtOH) to yield subfractions, which were further separated by preparative HPLC to obtain 13 individual compounds. Results: Extracts obtained from Ziziphora clinopodioides subsp. bungeana (Juz.) Rech.f. herb were subjected to pharmacological screening for the evaluation of their efficacy on hemic hypoxia. Based on the obtained results, out of the sixteen tested extracts two (AR and US 60%) were selected for further evaluation of their cardiotropic activity. Modeling of chronic heart failure was carried out in accordance with the following stages: 1) anesthesia with chloral hydrate at a dose of 450 mg/kg, intraperitoneally, 2) artificial ventilation of the lungs, 3) thora-cotomy, 4) modeling of permanent ischemic or ischemic-reperfusion damage. Both extracts effected the in-dicators of contraction and output, comparable to the reference drug -Monopril. Based on the extraction methods used to obtain RAF and US60 and data from the literature, it can be assumed that they contain com-pounds with medium polarity, including polyphenols and terpenoids. At the next stage three previously unde-scribed monoterpenoid derivatives - Ziziphoric acid (1), Ziziphoroside D (2) and 6 & PRIME;-malonylziziphoroside A (3), along with two previously described megastigmane glucosides - blumenol C glucoside (4), blumenol C 9-O-(6 & PRIME;-O-malonyl-beta-D-glucopyranoside (5) and two previously described monoterpenoids 7a-hydroxymintlactone (6), 7-hydroxypiperitone (7) together with six polyphenols - pinocembrine-7-O-rutinoside (8), chrysine-7-O-rutinoside (9), acacetin-7-O-rutinoside (10), luteolin-7-O-rutinoside (11), rutin (12) and rosmarinic acid (13) were isolated from Z. clinopodioides subsp. bungeana extracts. Conclusion: Our results support the traditional use of Z. clinopodioides subsp. bungeana for the treatment of coronary diseases. As a result of Z. clinopodioides subsp. bungeana extracts screening in vivo, two extracts were selected as potential cardiotropic agents. Phytochemical analysis of the plant material led to the isolation of five terpenoid derivatives, two megastigmane glycosides, five flavonoids and one cinnamic acid derivative, which could be responsible for the reported biological activity. Future experiments are required to understand the mechanisms of action for the isolated compounds.

The brain has a well-developed vascular network that allows it to consume up to 15% of cardiac output at its low weight relative to the whole-body weight. Normally, metabolic demands of the brain depend considerably on the intensity of functioning of its different regions, which requires a continuous local blood flow regulation. On the other hand, the state of systemic hemodynamics exert a significant impact on the organ blood flow. Complex and multilevel regulatory mechanisms of cerebral blood flow are aimed at minimizing possible adverse effects of systemic hemodynamic disorders. The importance of a precise and prompt cerebral blood flow regulation is reinforced by the lack of energy reserves or substrates for autonomous energy production in nervous tissue. The major mechanisms of cerebral blood flow regulation include myogenic regulation, local exposures to systemic blood flow humoral factors and vasoactive substances (hormones, metabolites), changes in blood gas composition (rises and falls in blood oxygen or carbon dioxide tension). Moreover, there are endothelium-dependent regulatory mechanisms. Yet another level of cerebrovascular tone regulation is represented by the impact of neurotransmitters released from vasomotor nerve terminals of sympathetic and parasympathetic divisions of the autonomic nervous system, as well as from synaptic endings of subcortical neurons and cortical interneurons. The present review addresses the principles of neurogenic regulation of cerebral blood flow. Neurogenic vascular tone regulation is the most complex regulatory circuit. The autonomic cerebrovascular innervation has significant features that distinguish it from that in most other organs of the great circle of blood circulation. Apart from autonomic innervation as such, brain vessels receive sensory inputs, while small intracerebral arterioles are additionally innervated directly by the neurons of subcortical nuclei and by cortical interneurons. Therefore, a deeper insight into the molecular mechanisms of cerebral blood flow neurogenic regulation may serve as a basis for the development of new neuromodulation-based therapeutic approaches to severe brain diseases.

Introduction. Combination therapy of chronic heart failure (CHF) is an urgent and important treatment strategy, as it allows to achieve an improvement in the prognosis, optimal control of the symptoms of the disease and an increase in the quality of life of patients.Aim. Comparison of the effectiveness of the malonic acid derivative ethmaben, the sodium-glucose cotransporter inhibitor empagliflozin and their combinations with the variability of the starting drug in experimental post-infarction chronic heart failure in rats.Materials and methods. In a model of post-infarction chronic heart failure, reproduced by permanent ligation of the left coronary artery in rats, an echocardiographic study was used to compare etmaben and empagliflozin monotherapy with a combined regimen of these drugs. The concentration of etmaben in the myocardium was assessed by HPLC.Results and discussion. Antagonism between etmaben and empagliflozin was revealed, manifested by a decrease in the effect of combination therapy in relation to any of the components, a decrease in the concentration of malonic acid derivative in the myocardium under the action of a type 2 sodium-glucose cotransporter inhibitor was shown.Conclusion. Based on the data obtained, additional studies of pharmacokinetics and pharmacodynamics of etmaben were planned.

We present the results of experimental studies into the pharmacological safety of a pharmaceutical substance 4-[(3-oxo-3-ethoxypropanoyl)amino]benzoic acid (Etmaben) under a single intragastric administration at various experimental doses (60–3000 mg/kg) to female laboratory outbred rats. A clinical examination of the experimental animals was carried out in order to identify signs of intoxication. To that end, the level of food and water consumption was assessed and biochemical blood tests were performed. In addition, the state of the central nervous and cardiovascular systems, physical endurance, and respiratory rate were assessed. The tested pharmaceutical substance in the studied doses after a single intragastric administration to female rats had no negative effect on the behavior, blood parameters, the state of the central nervous system and the cardiovascular system of experimental animals.

Here we developed a model of chronic thromboembolic pulmonary hypertension (CTEPH) using repeated intravenous administration of microencapsulated thrombi with a controlled rate of biodegradation. Autologous thrombi encapsulated in alginate microspheres with a diameter of 190±48 μm were intravenously injected to rats 8 times every 4 days. In the comparison group, nonmodified thrombi were injected. After 6 weeks, a significant increase in systolic pressure in the right ventricle, a decrease in exercise tolerance, and an increase in the index of vascular wall hypertrophy were revealed in the group receiving injections of microencapsulated thrombi in comparison with the group receiving nonmodified thrombi and healthy animals. Thus, the developed representative CTEPH model can be used to test promising pharmacological substances.

Acute cerebrovascular accident is one of the leading causes of disability and death worldwide. Given the significant increase in life expectancy of the population, stroke will remain a serious medical and social problem in the next few decades. Among the various causes of stroke, ischemic brain damage predominates. Ischemic stroke is based on a decrease in the intensity of blood supply to the brain tissues, as a result of which there is a decrease in the delivery to neurons of the required amount of glucose and oxygen, which are required to ensure the normal function of this organ. At the same time, in many cases, spontaneous or medical restoration of blood flow after a period of ischemia is accompanied by a paradoxical increase in damage, and therefore it is advisable to consider the process of damage to brain tissue during circulatory disorders in the context of ischemic-reperfusion injury (IRI). One of the key mechanisms of brain IRP is the inflammatory response. In the process of secondary immune damage to the brain, both mechanisms of innate immunity, manifested by leukocyte infiltration of the damaged brain area, and antigen-dependent reactions of adaptive immunity are involved. One of the most important manifestations of neuroinflammation in cerebral IRI is an increase in transand paracellular permeability of the blood-brain barrier, which underlies the development of vasogenic cerebral edema and hemorrhagic transformation of the focus. This review considers current ideas about the molecular mechanisms that link aseptic inflammation, edema, and hemorrhagic transformation.

Personality and affective computing techniques play a significant role for better understanding of human’s behavior and intentions. Such techniques can be applied in practice in recommendation systems, healthcare, education, and job applicant screening. In this paper, we propose a novel multimodal approach to personality traits assessment that leverages affective features of human’s voice and face, as well as recent advances in the deep learning. We present a new mid-level modality fusion strategy that is based on a cross-modal attention mechanism with summarizing functionals. In contrast to other state-of-the-art approaches, we not only analyze a visual scene, but specifically process human’s upper body (selfie) and a scene background. Our experiments show that the Extroversion personality trait is better estimated by fusing visual scene, face, and audio (voice) modalities, while the Conscientiousness and Agreeableness traits are better assessed by fusing face, selfie, and audio modalities. Furthermore, our results show that utilizing the selfie modality outperforms the visual scene modality by more than 1% in terms of the Concordance Correlation Coefficient. Additionally, our approach based on processing three modalities (selfie, face, and audio) is on-par with other known state-of-the-art approaches that employ at least four modalities on the test set of the ChaLearn First Impressions V2 corpus.

Introduction. With the emergence of empagliflozin in the pharmaceutical market, there has been an increase in publications on the primary and secondary pharmacodynamics of the drug, and the list of potential indications for the use of this sodium-glucose co-transporter inhibitor is increasing. Hypotheses about pharmacological effects and mechanisms of their implementation are tested both in large-scale clinical studies and in animal experiments. Aim. The purpose of this work was to study the effectiveness of empagliflozin by echocardiographic, histological and molecular biological analyses at the three most significant points of the dynamic transition from acute myocardial infarction to post-infarction chronic heart failure in laboratory male rats. Materials and methods. The experiment was performed on 60 male outbred rats. Myocardial infarction was modeled in narcotic animals by permanent ligation of the left coronary artery. Based on echocardiographic (EchoCG) study data, animals were randomized to two groups: control infarction: untreated pathology group treated with placebo and pathology group treated with empagliflozin 1 mg/kg per os intragastric daily from the first day of the experiment. At 10, 20 and 30 days after the operation, the animals were also subjected to EchoCG testing, and a group of 10 animals from each group were euthanized for histological examination and molecular analysis. Results and discussion. Empagliflozin use in animals after myocardial infarction modeling contributed to a significant increase in myocardial performance on days 10, 20 and 30, reaching a maximum on day 20 (47.58 ± 1.87 %). The drug promotes long-term preservation of the area of damage to the heart muscle with early formation of mature connective tissue, and also increases myocardial resistance to hypoxia by increasing the amount of HIF-1. Conclusion. Based on the studies carried out, it can be concluded that it is possible to use the sodium-glucose cotransporter type 2 empagliflozin in the formation of post-infarction chronic heart failure in the conditions of normoglycemia.

Background . The formation of a pseudarthrosis is one of the most severe complications of bone fractures. Pseudarthrosis occurs as a result of a disorder in the fracture union, has a poor prognosis and requires long-term treatment and repeated surgeries. A small number of representative pseudarthrosis models makes it difficult to conduct preclinical studies of promising pharmacological substances, bone replacement materials and surgical methods of treatment. The aim . To develop and to validate an experimental model of normotrophic pseudarthrosis of a rabbit’s tibia by creating diastasis between bone fragments, forming local vascularization disturbance and using unstable fixation. Materials and methods . The study was carried out on Soviet Chinchilla rabbits. The animals were divided into 2 groups: in experimental group, we formed tibial pseudarthrosis; in control group, we made a simple transverse tibial fracture. The pseudarthrosis was formed by segmental resection (5 mm) of the middle third of the tibia, bone fragments dilatation for 5 mm, removal of periosteum and bone marrow within 5 mm followed by daily destabilization of a fracture in an external fixation device. The duration of the experiment was 6 weeks. X-ray examination of the fracture area was carried out weekly, multi-layer spiral computed tomography (MSCT) and histological examinations were carried out at the end of the experiment. Results . The survival value in the experiment was 100 %. According to weekly X-ray examination, fracture union was registered only in the control group and occurred on average on the 22,8 ± 5,1 day, while the formation of pseudarthrosis was observed only in the experimental group, and radiographic signs of a pseudarthrosis were noted on average on the 33,6 ± 3,5 day. The formation of a pseudarthrosis by the end of the experiment was confirmed by MSCT and histological studies. Conclusions . The developed model of the normotrophic pseudarthrosis of a rabbit’s tibia can be used for experimental tests of various factors for stimulating reparative regeneration and methods for treatment of the pseudarthrosis.

Introduction: The solution of the task of the recognition and assessment of user engagement in the acts of human-machine interaction or telecommunication, achieved through the use of automatic means, is highly important in computer recognition of human psycho-emotional states. This is necessary for e-learning, business and entertainment applications design. Purpose: To conduct a comparative analysis of the current information support in the field of automatic recognition and assessment of user involvement in human-machine interaction or virtual communication, as well as to establish a methodology for building a data body based on the idea of multimodal communication. Results: The conducted analysis of research papers has shown that in most existing databases there is a substantial lack of data for natural online communication. Moreover, not all databases contain different modalities in “human-machine-human” communication system. Text and audio modalities turn out to be important for a multilevel engagement classification task, aimed at the determination of engagement intensity. It is also promising to take into account “body language” features, such as facial expressions, movements of the body and the head, gestures. For the correct assessment of involvement, an engagement database must contain meta-data on the psycho-emotional states of communicants. Neural network-based approaches to the automatic detection of user engagement show the best performance. Practical relevance: Based on the obtained analytical conclusions, the authors of the paper are going to elaborate an original software system for automatic recognition of user engagement, and to collect a data set for machine learning purposes. The presented review formulates basic requirements for such systems and contributes to the solution of the problem of automatic recognition of psycho-emotional states. Discussion: The survey leads to the conclusion that the notion of engagement as understood in studies on automatic emotion recognition differs from that used in psychology. User (or communicant) engagement in terms of info- and communicative sphere implies the manifestation of a person's mental activity level (emotional, cognitive, and behavioral components) changing dynamically while interacting with another person or computer system.

Introduction. Chronic thromboembolic pulmonary hypertension (CTEPH) is the most common complication of pulmonary thromboembolism (PE). Fibrous remodeling of the pulmonary circulation vessels against the background of CTEPH leads to an irreversible increase of the vessel wall stiffness and the ineffectiveness of CTEPH treatment. The involvement of Janus kinase (JAK) in the regulation of vascular wall and lung tissue inflammation and fibrosis allows for the possible effectiveness of JAK 1,2 inhibitors (iJAK) in the course of CTEPH. Purpose – to study the antifibrotic effect of iJAK for the prevention and treatment of CTEPH. Materials and methods. The study was conducted on male Wistar rats. Modeling of CTEPH was performed by sequential embolization of the vascular bed with partially biodegradable sodium alginate microspheres. 2 weeks after the last administration of the microspheres, low, medium and high doses of iJAK were initiated. To assess the effectiveness of the substance, the following tests were used: treadmill test, echocardiography, cardiac catheterization with right ventricular (RV) manometry, histological examination of the lungs. Results. Animals undergone vascular embolization demonstrated decreased exercise tolerance at all observation points compared to healthy animals. The placebo group, in contrast with the group getting treatment and iJAK, was found to have an increased mean RV pressure compared to healthy animals. There was an increase in mean RV pressure in the placebo group (15.5±7.7 mmHg) and in the low dose and iJAK group (13.4±6.4 mmHg) compared with healthy animals (9.4±2.2 mmHg). Vascular hypertrophy of the pulmonary artery branches was lower in group getting average dosages and iJAK compared with the placebo group (54.9±19.0 and 68.9±23.1 %, respectively). Thus, the suppression by iJAK of aseptic inflammation and following fibrosis leads to the decreasing of severity of pulmonary circulation remodeling in the experimental model of CTEPH. This approach can be used in the comprehensive bypass and prevention of CTEPH.

An entire cycle of preclinical studies of 4-[(3-ethoxy-3-oxopropanoyl)amino]benzoic acid (etmaben) exhibiting cardiotropic action was carried out. Its potential action mechanism and pharmacological effects, general toxic effects in acute and chronic experiments, specific types of toxicity (allergenicity, immunotoxicity, reproductive toxicity, mutagenicity), and pharmacokinetics were studied. The drug was found to have a pronounced cardiotropic effect and a positive safety profile, which justifies the launch of phase I clinical trials.

The article presents theoretical and empirical materials that reveal the specifics of the main parameters of the metacognitive sphere of personality as determinants of general management styles. It is shown that one of the most constructive means of such disclosure is to identify the relationship between management styles as one of the central constructs of management psychology, on the one hand, and the main metacognitive parameters (procedural, strategic and other characteristics), on the other. The regularities of the influence of metacognitive factors on the main general management styles are established. It is shown that they are characterized by different values of the indexes of integration (coherence), differentiation (divergence) and the index of general organization of the metacognitive sphere. The provisions are formulated according to which general management styles have a structural, rather than analytical determination in relation to those metacognitive factors on the basis of which they are formed.