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The objective is to determine the complete nucleotide sequence and conduct a phylogenetic analysis of genome variants of the Puumala virus isolated in the Saratov region. Materials and methods. The samples for the study were field material collected in the Gagarinsky (formerly Saratovsky), Engelssky, Novoburassky and Khvalynsky districts of the Saratov region in the period from 2019 to 2022. To specifically enrich the Puumala virus genome in the samples, were used PCR and developed a specific primer panel. Next, the resulting PCR products were sequenced and the fragments were assembled into one sequence for each segment of the virus genome. To construct phylogenetic trees, the maximum parsimony algorithm was used. Results. Genetic variants of the Puumala virus isolated in the Saratov region have a high degree of genome similarity to each other, which indicates their unity of origin. According to phylogenetic analysis, they all form a separate branch in the cluster formed by hantaviruses from other subjects of the Volga Federal District. The virus variants from the Republics of Udmurtia and Tatarstan, as well as from the Samara and Ulyanovsk regions, are closest to the samples from the Saratov region. Conclusion. The data obtained show the presence of a pronounced territorial confinement of strains to certain regions or areas that are the natural biotopes of their carriers. This makes it possible to fairly accurately determine the territory of possible infection of patients and/or the circulation of carriers of these virus variants based on the sequence of individual segments of their genome.

The objective was to study the degree of deviations of laboratory parameters of the systemic inflammatory response syndrome (SIRS) under the conditions of modulation of the reactions of the sympathetic nervous system by various α-2-adrenergic receptors during neurosurgical interventions for the removal of the brain tumor of subtentorial localizationMaterials and methods. The laboratory data of 179 patients operated for the brain tumor of subtentorial localization were analyzed. The operations were performed under conditions of total intravenous anesthesia. The patients were divided into two groups depending on the α-2-adrenergic agonist used in the structure of the anesthetic aid: clonidine was used in the first group, dexmedetomidine was used in the second group. Laboratory tests included analysis of the levels of cytokines (IL-8, IL-6, IL-10, TNF-α), CRP, fibrinogen. Blood sampling for the study was carried out in five stages: 1 – one day before the operation, 2 – on the day of the operation before the introductory anesthesia, 3 – after the induction anesthesia, 4 – after removal of the tumor (at the stage of hemostasis); 5 – on the first day after surgery.Results. The dynamics of laboratory parameters were similar in both study groups and reflected the manifestations of the systemic inflammatory response of the body to intracranial intervention. The levels of pro-inflammatory cytokines IL-6, IL-8, TNF-α, and C-reactive protein (CRP) increased in the fourth and fifth stages of the study. The increase in the level of IL-6 and fibrinogen in the fifth stage of the study in the second group was more significant, which was explained by the less pronounced anti-inflammatory effect of dexmedetomidine compared to clonidine.Conclusions. Changes in laboratory parameters of SIRS as the reaction to surgical intervention on the brain were transient. Under conditions of total intravenous anesthesia with the use of α-2-adrenergic agonists, modulation of the inflammatory response was demonstrated, which ensured adequate consistency of the inflammatory process.

Purpose. Search and presentation of data from experimental and clinical studies reflecting the central role of succinate and succinate dehydrogenase in the regulation of adaptation mechanisms in critical conditions. Material and methods. The search for literature sources was carried out using the electronic resources of the Russian scientific electronic library eLIBRARY.ru, with the use of the following keywords: «Krebs cycle, succinate, succinate dehydrogenase, critical conditions», as well as in the English-language text database of medical and biological publications on medical sciences PUBMED, where similar keywords «Krebs cycle, succinate, succinate dehydrogenase, critical conditions» were used. Results. Taking into account the data presented in the review, it can be stated that the complex of succinate and succinate dehydrogenase is the central link in the Krebs cycle and the main structure of the antihypoxic ensemble of all body cells during the adaptation period under critical conditions. Conclusion. The data of experimental and clinical studies reflecting the central role of succinate and succinate dehydrogenase not only in the mechanisms of adaptation to hypoxia, but also in the regulation of inflammation, thermogenesis, hemostasis disorders, acid-base state, electrolyte metabolism, vascular tone and trophism of intestinal tissues, as well as in immunological reactions of the body, allow us to consider the substrate and enzyme as the central link of the Krebs cycle and the main structure of the antihypoxic ensemble of all body cells. The data presented in the review open up new prospects for the use of succinates in critical conditions.

Paroxysmal sympathetic hyperactivity (PSH) is one of the complications of acute severe brain injuries (traumatic brain injury, intracranial hemorrhage, ischemia, and posthypoxic conditions) in both adults and children. Its high incidence and severe sequelae including organ dysfunction, infectious complications, impaired blood supply to organs and tissues associate with increased disability and mortality. The choice of effective therapy can be challenging because of multifaceted manifestations, diagnostic difficulties, and lack of a clear understanding of the pathophysiology of PSH. Currently, there are various local and international treatment strategies for PSH.The aim of the review is to summarize clinical and scientific research data on diagnosis and treatment of PSH to aid in the selection of an effective therapy.Material and methods. Web of Science, Scopus and RSCI databases were employed to select 80 sources containing relevant clinical and research data on the subject of this review.Results. The key principles of diagnosis and treatment of paroxysmal sympathetic hyperactivity have been reviewed. The current views on etiology and pathogenesis of paroxysmal sympathetic hyperactivity development were outlined. The clinical data concerning complications and sequelae of paroxysmal sympathetic hyperactivity were analyzed. We conclude the review with a discussion of current methods of the syndrome prevention.Conclusion. Preventing PSH and its adequate and prompt treatment could help avoid the abnormal pathway development following a severe brain injury, reduce its negative consequences and rate of complications, along with the duration of mechanical lung ventilation, patient's stay in ICU, disability and mortality rates. Careful selection of pathogenetic, symptomatic and supportive therapy significantly improves the rehabilitation potential of patients.

Anesthesia including drugs that act on the opioid (fentanyl) and adrenergic (clonidine or dexmedetomidine) neuroregulatory systems, creates optimal conditions for performing brain surgery.The objective: to study the effect of combination of opioid analgesic fentanyl and alpha2-adrenoagonists on stability (reactivity) and appropriate functional activity of the circulatory system.Subjects and Methods. The study included 118 patients operated on for a brain tumor. Patients were divided into groups depending on the alpha2-adrenoagonist used, its dosage and position on the operating table.Results. In all groups, the required level of neurovegetative stabilization with stable hemodynamics was achieved at all stages of the operation. Conclusion. Studies have shown that a lower dose of dexmedetomidine versus clonidine was required to achieve a central sympatho-modulatory effect.

Spontaneous pneumomediastinum is a rare complication of viral pneumonia. The prevalence of pneumomediastinum among coronavirus infection patients is unknown.Subjects and methods. Three cases of spontaneous pneumomediastinum among the COVID-19 pneumonia patients were analyzed. The researchers investigated and compared clinical, radiological and laboratory data.Results. According to the research results, no correlation was found between the development of pneumomediastinum and changes in values of blood laboratory tests. As well as there were no signs of correlation between drug treatment and pneumomediastinum frequency.Conclusion: The researchers suggest that the leading cause of spontaneous pneumomediastinum is viral pneumonia-associated severe alveolar damage.

Introduction: Changes in hormonal status in patients with prolonged disorders of consciousness (PDC) remain poorly understood. There are no studies devoted to the investigation of prognostic value of hormonal changes to predict the outcome which is primarily due to a relatively small number of patients, different variants of structural brain disorders in vegetative state (VS) patients, concomitant somatic pathology including typical complications.The objective: to study the correlation between outcomes in VS patients with hormonal status and the level of natriuretic peptide. Subjects and methods. 275 patients in VS were examined for the time period from 2007 to 2017. 152 patients had sequela of traumatic brain injury (TBI) and 123 patients suffered from hypoxic brain damage. All patients matched the international criteria of VS diagnosis. In all patients, blood samples were collected during the first week after admission to ICU to test hormones and natriuretic peptide levels. ACTH, cortisol, TSH, free T3 and T4 , STH, prolactin and natriuretic peptide were tested in the period from 2 to 4 months of staying in VS. In men, the level of total testosterone, LH and FSH was additionally tested. The obtained data were compared with VS outcome.Results. The tested hormones were stably insufficient only in few VS patients. None of the tested hormones of the hypothalamic-pituitary-adrenal axis made a reliable criterion for predicting VS outcome. The tendency of disrupted rhythm of cortisol secretion was found to be most frequent and consistent, with higher rates in the evening hours. The average value of STH was higher in men with sequela of traumatic brain injury who had recovered consciousness versus those who remained in VS. A significant decrease in testosterone levels, regardless of age, was found in the patients with TBI sequela. Mean levels of LH were higher in patients with TBI sequela and hypoxia who remained unconscious versus patients who later restored consciousness. The average level of FSH was higher in patients who had recovered consciousness compared to those who remained in chronic VS. The increased level of natriuretic peptide was observed both in patients who remained in chronic VS and in those who restored consciousness.Conclusions. When investigating levels of certain hormones, no specific endocrine background characterizing this category of patients was found. Abnormal rhythms of some hormones secretion, in particular cortisol, can be considered typical of VS patients especially patients with TBI sequela.

Schizophrenia has a heritability of 60-80% 1 , much of which is attributable to common risk alleles. Here, in a two-stage genome-wide association study of up to 76,755 individuals with schizophrenia and 243,649 control individuals, we report common variant associations at 287 distinct genomic loci. Associations were concentrated in genes that are expressed in excitatory and inhibitory neurons of the central nervous system, but not in other tissues or cell types. Using fine-mapping and functional genomic data, we identify 120 genes (106 protein-coding) that are likely to underpin associations at some of these loci, including 16 genes with credible causal non-synonymous or untranslated region variation. We also implicate fundamental processes related to neuronal function, including synaptic organization, differentiation and transmission. Fine-mapped candidates were enriched for genes associated with rare disruptive coding variants in people with schizophrenia, including the glutamate receptor subunit GRIN2A and transcription factor SP4, and were also enriched for genes implicated by such variants in neurodevelopmental disorders. We identify biological processes relevant to schizophrenia pathophysiology; show convergence of common and rare variant associations in schizophrenia and neurodevelopmental disorders; and provide a resource of prioritized genes and variants to advance mechanistic studies., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

We report the soliton frequency comb generation in microring optical parametric oscillators operating in the downconversion regime and with the simultaneous presence of the χ (2) and Kerr nonlinearities. The combs are studied considering a typical geometry of a bulk LiNbO 3 toroidal resonator with the normal group velocity dispersion spanning an interval between the pump and the downconverted signal. We have identified critical power signaling a transition between the relatively low pump power predominantly χ (2) combs and the high pump power ones shaped by the competition between the χ (2) and Kerr nonlinearities.