[The interactions along the microbiota-gut-brain axis in the regulation of circadian rhythms, sleep mechanisms and disorders]. / Rol' vzaimosvyazei po osi mozg­kishechnik­mikrobiom v regulyatsii tsirkadiannykh ritmov, mekhanizmakh sna i ikh narushenii.

The bidirectional relationship between cerebral structures and the gastrointestinal tract involving the microbiota embraces the scientific concept of the microbiota-gut-brain axis. The gut microbiome plays an important role in many physiological and biochemical processes of the human body, in the immune response and maintenance of homeostasis, as well as in the regulation of circadian rhythms. There is a relationship between the higher prevalence of a number of neurological disorders, sleep disorders and changes in the intestinal microbiota, which actualizes the study of the complex mechanisms of such correlation for the development of new treatment and prevention strategies. Environmental factors associated with excessive light exposure can aggravate the gut dysbiosis of intestinal microflora, and as a result, lead to sleep disturbances. This review examines the integrative mechanisms of sleep regulation associated with the gut microbiota (the role of neurotransmitters, short-chain fatty acids, unconjugated bile acids, bacterial cell wall components, cytokines). Taking into account the influence of gut dysbiosis as a risk factor in the development of various diseases, the authors systematize key aspects and modern scientific data on the importance of microflora balance to ensure optimal interaction along the microbiota-gut-brain axis in the context of the regulatory role of the sleep-wake cycle and its disorders.

Responses of soil physico-chemical properties, structure of the microbial community and crop yields to different fertilization practices in Russia's conventional farming system.

The use of fertilizers affects not only the soil fertility and crop yield, but also significantly changes the taxonomic structure of the soil microbiocenosis. Here, based on stationary field experiment, we studied the influence of organo-mineral fertilizer (ОМF), modified by bacteria Bacillus subtilis, H-13 in comparison with different fertilizer systems (organic, mineral, organo-mineral) on (i) crop yield, (ii) physical and chemical properties, and (iii) alpha and beta diversity of the microbial community Albic Retisol (Loamic, Aric, Cutanic, Differentic, Ochric). The studies were carried out against the background of liming (рНКCl - 5.9) and without it (рНКCl - 5.1). The use of only one cattle farmyard manure was less effective than its co-application with mineral fertilizers in half doses. A similar effect was obtained when applying ОМF. In addition, the use of OMF contributes to a significant increase in the reserves of soil organic carbon in the soil layer 0-20 cm by 18%-32%. Using high-throughput sequencing of the 16S rRNA variable V4 gene sequence libraries, 10.759 taxa from 456 genera were identified, assigned to 34 fila (31 bacterial and 3 archaeotic. Unilateral application of mineral fertilizers leads to a significant decrease in the alpha diversity of the structure of soil microbial communities (OTE (other things equal) and Shannon index). A clear clustering of the microbiota was found in the variants with and without the introduction of сattle farmyard manure. It is revealed that the taxonomic structure of the microbiocenosis is formed under the influence of two main factors: crop rotation culture and applied fertilizers. The type of cultivated crop determines the dynamics of the microbiota at the level of larger taxa, such as domains, and fertilizers affect the structure of the microbial community at a lower taxonomic level (phyla, orders, bloodlines). On the basis of the Deseq analysis, marker taxa were identified, according to the share participation of which it is possible to determine the type of cultivated crop and fertilizers used in the experiment. Understanding the dynamics of taxa association and other influential factors can lead to the creation of universal systems of metagenomic indication, where tracking the dynamics of microbial communities will allow for a comprehensive assessment of the agroecological state of soils and timely decisions to prevent their degradation.

[Genetics of sucrose metabolism disorders in different population groups].

The study of the genetic determinants of the disaccharidase activity opens up new prospects for improving diagnostics and choosing medical tactics in gastroenterology. The aim of the study was to systematize the data on the role of the sucrase-isomaltase gene (SI) in regulating sucrose metabolism and the contribution of SI mutations to the prevalence of sucrose malabsorption disorders (sucrase-isomaltase deficiency, SID) and certain forms of enterological pathology in different population groups. Material and methods. A review of the peer-reviewed scientific literature, mainly in the PubMed database (https://pubmed.ncbi.nlm.nih.gov) and eLibrary (https://elibrary.ru), was conducted using key words: carbohydrate malabsorption, sucrase, sucrase-isomaltase deficiency, sucrase-isomaltase SI gene. The search depth was not specified, but particular attention was paid to recent publications. The gnomAD database (https://www.ncbi.nlm. nih.gov/snp/rs781470490) was also used. Results. According to the review results, 37 out of 150 known SI gene mutations have been confirmed to contribute to reduced sucrase activity or restricted sucrase production. The prevalence of point mutations in the SI gene is estimated at 0.0006%, but carrier rates of the SI delAG deletion (rs781470490), manifested as homozygosity in SID, are very high (5-21%) in indigenous populations of Arctic regions in East Asia and America. Medicalgenetic research methods improve the accuracy of differential diagnosis of primary and secondary SID and other forms of disaccharide and polysaccharide malabsorption. The formation of databases on the prevalence of genetic determinants of sucrase-isomaltase insufficiency is a promising way to refine the epidemiology of SID. There is an increased (0.2-2.3%) risk of clinical manifestations of SID in homozygous carriers of the SI delAG mutation in the Chukotka, Kamchatka, and Northern Priochotye populations. Verification of reports on a less pronounced tendency to lipid metabolism disorders in SI delAG carriers compared with the control group is recommended. Conclusion. Manifestations of mutant SI variants in the phenotype are associated with the presence of accompanying carbohydrate malabsorption variants and specific gut microbiota. The SI 15Phe variant (rs9290264) may contribute to the development of irritable bowel syndrome.

[Convexity hyperostotic meningioma en plaque: a systematic review]. / Ploskostnye giperostoticheskie meningiomy svoda cherepa. Sistematicheskii obzor literatury.

BACKGROUND: Planar hyperostotic meningiomas account for 2-9% of intracranial meningiomas. They are characterized by planar node following the contours of the inner surface of the skull. Hyperostosis is present in most cases. Timely diagnosis of skull base tumors is usually simple due to early involvement of the cranial nerves. However, convexity meningiomas en plaque usually reach large dimensions that complicates surgery and radiotherapy. OBJECTIVE: To analyze the current state of diagnosis, molecular biology and surgical treatment of hyperostotic meningiomas en plaque. MATERIAL AND METHODS: A systematic review was performed in accordance with the PRISMA guidelines. Searching for literature data included the following keywords: «planar meningioma¼, «hyperostotic meningioma¼, «meningioma en plaque¼, «infiltrative meningioma¼. We reviewed the PubMed and Google Scholar databases until May 2023 and enrolled only full-text Russian-, English- or French-language reports. RESULTS AND DISCUSSION: Among primary 332 reports, 35 references met the inclusion criteria. We found less severity or absence of focal neurological symptoms, comparable incidence of intracranial hypertension and no histological differences between planar and nodular meningiomas. Analysis of molecular biological features of planar meningiomas, including cell cultures, is feasible. There is no consensus regarding surgical treatment and radiotherapy. Most publications are case reports. CONCLUSION: The results of treatment of planar hyperostotic meningiomas, especially large and giant ones, are unsatisfactory. There is no a generally accepted algorithm for treating patients in the literature. This problem requires further research.

[Perifocal edema and glymphatic system dysfunction: quantitative assessment based on diffusion tensor magnetic resonance imaging]. / Peritumoroznyi otek i disfunktsiya glimfaticheskoi sistemy golovnogo mozga: kolichestvennaya otsenka na osnove diffuzionno-tenzornoi MRT.

BACKGROUND: Pathogenesis of peritumoral cerebral edema is unclear and potentially associated with glymphatic system dysfunction. Diffusion tensor MRI (DT-MRI) with analysis of ALPS (Analysis along the Perivascular Space) index may be valuable for assessment of edema. This approach visualizes fluid flow along perivascular spaces of deep cerebral veins. OBJECTIVE: To assess glymphatic system function in supratentorial tumors and healthy volunteers using DT-MRI. MATERIAL AND METHODS: There were 52 patients (59% men) aged 43 (28-64) years with supratentorial tumors (meningioma - 20, grade 3-4 glioma - 15, metastases - 9, lymphoma - 8). Tumors and perifocal edema did not involve deep cerebral veins. The control group included 6 healthy volunteers aged 34-66 years. MRI protocol (Signa HDxt, 3 T) contained standard T1, T2, T2FLAIR, DWI and post-contrast T1 (3D BRAVO). DT-MRI had the following parameters: TR=10 000 ms, TEmin=102 ms, FOV=240 mm, isotropic voxel size 3×3×3 mm3, 60 directions of diffusion gradients. Measurements were carried out at b-factor 0 and 1000 s/mm2. Analysis was carried out in the ReadyView software. RESULTS: Right- and left-sided ALPS indices were similar in the control group (p=0.917). Perifocal edema (regardless of histological type of tumor) in the ipsilateral hemisphere was accompanied by significantly lower ALPS index (p<0.005), while these values in contralateral (intact) hemisphere were similar in both groups (p=0.7). CONCLUSION: We found significantly lower ALPS index in deep parts of the affected hemisphere in patients with perifocal edema. These data can indicate the role of glymphatic system dysfunction in pathogenesis of this pathology.

[Comparison of methods of treatment of meningiomas invading the superior sagittal sinus]. / Sravnitel'naya otsenka metodov lecheniya meningiom, invaziruyushchikh verkhnii sagittal'nyi sinus.

There are various approaches to the treatment of patients with parasagittal meningiomas. OBJECTIVE: To optimize treatment strategy for meningiomas invading the superior sagittal sinus. MATERIAL AND METHODS: The study included 87 patients with benign parasagittal meningiomas between 2010 and 2012. Of these, 34 patients underwent surgery alone, 27 - radiotherapy, 26 - surgery and subsequent radiotherapy. Both groups were comparable in male-to-female ratio, age and localization of tumors in relation to superior sagittal sinus. The follow-up period was at least 5 years. We analyzed the effect of treatment on neurological status, Karnofsky score and tumor growth control. RESULTS: Mean volume of tumors was 43.3 cm3 in patients undergoing surgery and 6.7 cm3 in the radiotherapy group. In the combined treatment group, mean volume was 65.8 cm3 before surgery and 8.8 cm3 before irradiation. General cerebral symptoms (84%), epileptic seizures (37%) and movement disorders (31%) prevailed. Surgery provided the best results in patients with small meningiomas (<14 cm3) causing focal neurological symptoms. Isolated radiotherapy was the most effective in asymptomatic patients. Large tumors required surgery with adjuvant irradiation. CONCLUSION: Benign parasagittal meningiomas followed by focal neurological symptoms require surgical intervention regarding the best functional outcomes and tumor growth control. Radiotherapy without surgery is advisable for progressive asymptomatic tumors. Resection followed by irradiation is preferable if total resection without the risk of damage to veins and cortex is impossible.

[New classification and approaches to the treatment of schwannomatosis]. / Novaya klassifikatsiya i podkhody k terapii shvannomatozov.

Schwannomatoses is a new classification unit for all the hereditary diseases caused by chromosome 22 damage followed by multiple benign neoplasms of the peripheral and central nervous system. Schwannomatosis occurs as a result of damage to different genes: NF2, SMARCB1, LZRT1, loss of heterozygosity of the long arm of chromosome 22. Nevertheless, clinical manifestations are similar. Molecular diagnostics not only confirms the diagnosis, but also predicts the course of disease. Thus, the most severe clinical manifestations are observed in patients with violation of semantic sequences and reading frame shift in exons 2-13 of the NF2 gene. A more favorable course with less number of tumors is observed in patients with somatic mosaicism. Stereotactic irradiation and surgery are the main treatment options for schwannomatosis. However, there is evidence of effective targeted therapy with bevacizumab (inhibitor of vascular endothelial growth factor). Bevacizumab is used in patients with bilateral vestibular schwannomas and high risk of hearing loss, as well as for intramedullary tumor growth control.

[Factors influencing peritumoral edema in meningiomas: CT- and MRI-based quantitative assessment]. / Peritumoroznyi otek pri meningiomakh i faktory, vliyayushchie na ego formirovanie: kolichestvennaya otsenka na osnove KT i MRT.

Background. Meningiomas may be accompanied by peritumoral edema. Incidence and pathogenesis of edema are nor clearly established. Prevalence and severity of edema vary significantly in patients with meningiomas similar in various parameters. OBJECTIVE: To assess peritumoral edema in intracranial meningiomas and factors influencing incidence and severity of this process. MATERIAL AND METHODS: There were 126 patients (69% women) aged 19-76 years (median 53), who were diagnosed with 142 meningiomas. Patients underwent surgery (n=111) and radiotherapy (n=15) in 2016-2018. The MRI protocol included T1, T2, T2-FLAIR, DWI and post-contrast T1-weighted images in three projections, diffusion tensor MRI in 27 cases and MR spectroscopy in 21 patients. RESULTS: Peritumoral edema was detected in 46% (n=66) of cases including 21 (31%) patients with severe edema. The ALPS index was 1.510±0.1931 in meningiomas without edema and 1.308±0.19 in those with edema (p=0.014). There was positive correlation between edema, dimensions and uneven contours of meningioma, as well as negative correlation with CSF cleft sign. Blood flow velocity was higher in atypical and anaplastic meningiomas with edema (p=0.03). Other signs (localization, histological variant, malignancy grade, characteristics of MR signal, peaks of the main metabolites, diffusion and perfusion parameters of tumor) did not significantly affect peritumoral edema in patients with meningiomas (p>0.05). CONCLUSION: Diffusion tensor tomography with ALPS index revealed significant effect of glymphatic system dysfunction on peritumoral edema. Large meningioma with uneven contours increased the risk of peritumoral edema, while CSF cleft sign reduced this risk. Other factors did not affect cerebral edema in meningiomas.

[Prevalence of trehalase enzymopathy genetic determinants in Siberian and Russian Far East populations].

To date, it has been established that the patient's genotype plays a significant role in the formation of trehalase enzymopathy: the level of enzyme activity decreases when the G→A allele replacement occurs in the rs2276064 locus of the TREH gene. To assess the prevalence of trehalase deficiency, extensive population-based studies are needed. Clinical observations show that the reduced activity of bowel trehalase is more common in the Arctic than in European populations. The aim of this research was to analyze the frequency of the alleles and variants of trehalase gene (rs2276064 TREH) in the indigenous small-numbered populations of Siberia and the Russian Far East. Material and methods. Using the Infinium iSelect HD Custom BeadChip biochip on the iScan platform and real-time polymerase chain reaction on a Bio-Rad CFX96 Touch amplifier, genotyping of 1068 DNA samples was carried out, of which 711 represent 10 ethnic groups of the indigenous people of the North of Siberia and the Far East of the Russian Federation. Two reference groups of Russians (n=311) and Yakuts (n=46) represented the "Caucasoid" and "Mongoloid" poles of the Russian population. Results. The reduced trehalase activity that the heterozygous GA*TREH genotype determines can manifest itself in 19.8-53.7% of indigenous northerners. An additional 1.0 to 19.7% of the population are carriers of the AA*TREH genotype, which is associated with apparent trehalose malabsorption. The carriers may experience nausea, abdominal pain, and other dyspeptic symptoms after eating trehalose containing foods. The total risk of trehalase enzymopathy among the indigenous northerners in the Asian part of the Russian Federation is very high and can reach 60-70%. There is a gradient in the A*TREH allele frequencies in the small-numbered indigenous northern groups of Russia from the west (Khanty, Mansi, Nenets) to the east (peoples of the Far East). Conclusion. The results are consistent with previously reported data on the higher carriage of the A*TREH mutant allele in Mongoloid populations compared to Caucasoid groups. It was hypothesized that, while the initial A*TREH allele prevalence in Mongoloid groups was moderately high, an adaptation to a low-sugar protein-lipid "high-latitude" diet led to a weaker control over the maintenance of the carriage of the ancestral G allele. Trehalose malabsorption requires special attention of specialists in the field of nutrition, gastroenterology, public health, and medical genetics working in high-latitude regions.

[Dural defect closure after resection of cranioorbital meningiomas]. / Rekonstruktsiya defektov tverdoi mozgovoi obolochki posle udaleniya kranioorbital'nykh meningiom.

Dural defect closure after resection of cranioorbital meningiomas has its own specifics. Extended malignant lesions and common large bone defects involving various anatomical regions require multiple implants or implants with complex geometry. The features of this stage of reconstruction were described in the previous issue of the Burdenko Journal of Neurosurgery. At the same time, contact of implant with nasal cavity and paranasal sinuses dictates additional requirements for tightness of soft tissue reconstruction and inertness of material. In this review, we describe modern and historically interesting methods of reconstruction of soft tissue defects following resection of cranioorbital meningioma. OBJECTIVE: To summarize and analyze available literature data on reconstruction of soft tissue defects following resection of cranioorbital meningioma. MATERIAL AND METHODS: The authors reviewed available data on reconstruction of soft tissue defects after resection of cranioorbital meningiomas. Effectiveness of reconstruction techniques and safety of materials were analyzed. RESULTS: The authors analyzed 42 available full-text articles. Features of growth and natural course of cranioorbital meningioma, methods of soft tissue defects closure, modern materials and sealing compositions are described. Considering these data, the authors proposed the algorithms for selecting materials for dural reconstruction after resection of cranioorbital meningioma. CONCLUSION: Improvement of surgical technique, development of new materials and technologies increase the efficiency and safety of dural defect closure. Nevertheless, high incidence of complications associated with dura mater repair necessitates further research in this area.

Search for the Majorana Nature of Neutrinos in the Inverted Mass Ordering Region with KamLAND-Zen.

The KamLAND-Zen experiment has provided stringent constraints on the neutrinoless double-beta (0νßß) decay half-life in ^{136}Xe using a xenon-loaded liquid scintillator. We report an improved search using an upgraded detector with almost double the amount of xenon and an ultralow radioactivity container, corresponding to an exposure of 970 kg yr of ^{136}Xe. These new data provide valuable insight into backgrounds, especially from cosmic muon spallation of xenon, and have required the use of novel background rejection techniques. We obtain a lower limit for the 0νßß decay half-life of T_{1/2}^{0ν}>2.3×10^{26} yr at 90% C.L., corresponding to upper limits on the effective Majorana neutrino mass of 36-156 meV using commonly adopted nuclear matrix element calculations.

[Bone defect closure after resection of sphenoorbital meningioma]. / Rekonstruktsiya kostnykh defektov posle udaleniya kranioorbital'nykh meningiom.

Sphenoorbital meningiomas (SOM) are a subgroup of skull base tumors with soft tissue component in the orbit and anterior and/or middle cranial fossa. According to different authors, SOMs account for 2-12% of all intracranial meningiomas. Reconstruction of bone defects after resection of SOM has own nuances. Along with cranial vault repair, patients encounter with cosmetic defects following facial skull lesion, ophthalmic symptoms due to orbital defects, dental and functional problems associated with opening of the mouth in case of damage to maxilla and mandible. Predominant infiltrative growth of tumor and common large bone defects involving various anatomical regions require multiple implants or implants with complex shape. Moreover, contact of implantation area with nasal cavity and paranasal sinuses requires additional impermeability of soft tissue reconstruction and inertness of materials. OBJECTIVE: To summarize available modern data on bone defect closure after resection of SOM. MATERIAL AND METHODS: The authors reviewed available data on bone defect closure after resection of SOM. Effectiveness of modern methods of reconstruction and safety of materials were assessed. RESULTS: We analyzed 96 available references. Technical features of tumor resection, materials used for bone defect closure and modern possibilities of 3D technologies in reconstructive surgery were described. The authors proposed the algorithms for selecting the materials for bone defect closure after resection of SOM. CONCLUSION: Improvement of surgical technique and development of new materials and technologies significantly improve cosmetic and functional results. A large percentage of negative ophthalmologic outcomes and high risk of complications in SOM surgery require further studies and elaboration of modern techniques.

[Hypertriglyceridemic pancreatitis and cardiac tamponade in a 26-year-old woman]. / Hypertriglyzeridämie-bedingte Pankreatitis und Perikardtamponade bei einer 26­jährigen Patientin.

A 26-year-old woman with type 2 diabetes mellitus and discontinued intensive conventional insulin therapy was admitted to the authors' hospital with acute upper abdominal pain. Severe hypertriglyceridemia and acute pancreatitis were diagnosed. Treatment included insulin administration and plasmapheresis. On day 3, the patient developed sudden haemodynamic instability and in-hospital cardiopulmonary arrest. Focused echocardiography showed pericardial effusion with right ventricular collapse. Pericardiocentesis was performed, leading to a return of spontaneous circulation.

[The influence of environmental factors on the prevalence of «thrifty genotypes¼ as predictors of metabolic disorders].

"Thrifty genotypes" are the risk factors for obesity and lipid and energy metabolism disorders. Hence, it is important to assess the contribution of environmental factors that influenced the thrifty genotypes' population distribution. Aim of the study - systematization and critical analysis of published data on population variability, relationship with climatic and environmental characteristics, association with traditional types of lifestyles, and nutrition for the «thrifty genotypes¼ of APOE, UCP1, UCP3, and FTO genes. Material and methods. The selection of publications from the last 20-25 years presented in the PubMed database (https://pubmed.ncbi.nlm.nih.gov) was carried out by the keywords of the generalizing rank (thrifty genotype, thrifty phenotype, drifty genotype), then narrowed down to the APOE, UCP, FTO. The final set includes publications that consider the association of genotypes with the ecological conditions of the population. Results. Our analysis of publications has confirmed the ethnic and geographical variability in the allele distribution of APOE, UCP1, UCP3, and FTO genes. However, the nature of this variability hasn't been studied sufficiently; the contribution of individual factors of the natural and anthropogenic environment remains unclear. The information on the geographical distribution of the APOE gene alleles is quite complete, while the data on the «thrifty genotypes¼ of UCP and FTO require further study. Conclusion. The frequency of the UCP1 and UCP3 alleles associated with effective non-contractile thermogenesis is increased in populations adapted to low temperatures. However, the population-geographical pattern of the UCP thrifty genotypes' variability as a determinant of increased fat deposition has been studied insufficiently. The carriage of FTO mutant variants increases the adaptability of groups with a traditional lifestyle and diet but is maladaptive in an urbanized environment. The influence of natural and ecological conditions on the formation of the FTO allele geographical distribution requires more attention. The results obtained allow us to propose the included groups' ranking according to the past environmental management and nutrition will facilitate the search for ecological factors that influenced the geographical distribution of genotypes (and, accordingly, populations with different levels of risk of metabolic disorders).

Effect of Lysine Acridone Acetate on the Level of Apoptosis and Expression of Apoptosis-Associated Proteins during Antioncogenic Therapy in Colorectal Cancer in Mice.

We studied the mechanism of action of cytostatics with the addition of lysine acridone acetate to evaluate the possibility of its use for improving the effectiveness of antioncogenic therapy in colorectal cancer. In Nude mouse model, the level of apoptosis (TUNEL) and expression of proteins CD95, p53, Bcl-2, histone H3, and Ki-67 (immunohistochemistry) were assessed in primary tumor biopsy specimens. It has been shown that cytostatic treatment led to stimulation of p53-mediated apoptosis and suppression of proliferation (Ki-67 expression) of tumor cells, and apoptosis level was increased in groups receiving lysine acridone acetate. H3 expression in the experimental groups was changed.

The Theory of Carcino-Evo-Devo and Its Non-Trivial Predictions.

To explain the sources of additional cell masses in the evolution of multicellular organisms, the theory of carcino-evo-devo, or evolution by tumor neofunctionalization, has been developed. The important demand for a new theory in experimental science is the capability to formulate non-trivial predictions which can be experimentally confirmed. Several non-trivial predictions were formulated using carcino-evo-devo theory, four of which are discussed in the present paper: (1) The number of cellular oncogenes should correspond to the number of cell types in the organism. The evolution of oncogenes, tumor suppressor and differentiation gene classes should proceed concurrently. (2) Evolutionarily new and evolving genes should be specifically expressed in tumors (TSEEN genes). (3) Human orthologs of fish TSEEN genes should acquire progressive functions connected with new cell types, tissues and organs. (4) Selection of tumors for new functions in the organism is possible. Evolutionarily novel organs should recapitulate tumor features in their development. As shown in this paper, these predictions have been confirmed by the laboratory of the author. Thus, we have shown that carcino-evo-devo theory has predictive power, fulfilling a fundamental requirement for a new theory.

Evaluation of the influence of the analytical characteristics of the microbiological blood study in bacteremia in a multidisciplinary hospital.

The culture method continues to be the "gold" standard for microbiological diagnosis of bloodstream infections. This is primarily due to the fact that the definition of the etiology of a generalized infectious process determines the etiotropic antibiotic therapy. To do this, it is necessary to conduct periodic microbiological monitoring of the prevailing microflora. To do this, in the present study, a retrospective analysis of the results of a microbiological blood test for sterility was performed in case of suspected bloodstream infections in a multidisciplinary hospital to assess the influence of analytical stage factors on the laboratory data obtained. Automatic hematological cultivators were used, identification was carried out based on the biochemical characteristics of microorganisms, as well as using time-of-flight mass spectrometry with matrix-activated laser desorption / ionization (MALDI-TOF MS). More than 10,000 research results were analyzed, the average microflora seeding rate was 15.1%. The analysis of the isolated microflora was carried out in 2 groups of positive results: at the beginning, the data obtained in the presence of growth in two vials at once were evaluated, then the positive results of blood cultures obtained in any one vial from a pair were studied. The predominance of gram-positive flora in the structure of microorganisms isolated from whole blood was revealed, the influence of cultivation conditions and the composition of thenutrient medium on the isolated flora was not found, however, a number of microorganisms, due to the specific characteristics of metabolism, were characterized by growth under strictly defined cultivation conditions. The presented study actualizes the need for constant microbiological monitoring in order to determine the prevailing hospital microflora, which can contribute to a timely response in order to limit the spread of highly virulent, aggressive, resistant strains of microorganisms leading to the development of generalized bloodstream infections.

[Mechanisms of apoptosis in drug-resistant epilepsy]. / Mekhanizmy apoptoza pri farmakorezistentnoi epilepsii.

Epilepsy is a chronic neurological disease with regular spontaneous seizures associated with neuroinflammatory, autoimmune and neurodegenerative processes. Approximately 40% of patients suffer from drug-resistant epilepsy, which leads to an increased risk of premature death, injury, irreversible brain damage, psychosocial dysfunction, and reduced quality of life. Apoptosis of neurons and glial cells of the brain is of great importance in the pathogenesis of epilepsy, especially drug-resistant epilepsy. Investigation of the mechanisms of apoptosis is necessary for the creation of a new generation of neuroprotective and anticonvulsant drugs, effective, in particular, in the case of drug-resistant epilepsy. The aim of the study was to analyze the mechanisms and role of apoptosis in epileptogenesis and the development of resistance. The review considers current data on the main mechanisms of apoptosis in epilepsy, especially its drug-resistant forms.

Mammalian tumor-like organs. 2. Mammalian adipose has many tumor features and obesity is a tumor-like process.

BACKGROUND: In previous publications, the author developed the theory of carcino-evo-devo, which predicts that evolutionarily novel organs should recapitulate some features of tumors in their development. MAIN TEXT: Mammalian adipose is currently recognized as a multi-depot metabolic and endocrine organ consisting of several adipose tissues. Although lipid-storing cells and proteins are ancient, the adipose organ as a whole is evolutionarily novel to mammals. The adipose expansion has remarkable similarities with the growth of solid tumors. These similarities are the following: (1) The capability to unlimited expansion; (2) Reversible plasticity; (3) Induction of angiogenesis; (4) Chronic inflammation; (5) Remodeling and disfunction; (6) Systemic influence on the organism; (7) Hormone production; (8) Production of miRNAs that influence other tissues; (9) Immunosuppression; (10) DNA damage and resistance to apoptosis; (11) Destructive infiltration in other organs and tissues. These similarities include the majority of "hallmarks of cancer". In addition, lipomas are the most frequent soft tissue tumors, and similar drugs may be used for the treatment of obesity and cancer by preventing infiltration. This raises the possibility that obesity, at least in part, may represent an oncological problem. The existing similarities between adipose and tumors suggest the possible evolutionary origin of mammalian adipose from some ancestral benign mesenchymal hereditary tumors. Indeed, using a transgenic inducible zebrafish tumor model, we described many genes, which originated in fish and were expressed in fish tumors. Their human orthologs LEP, NOTCH1, SPRY1, PPARG, ID2, and CIDEA acquired functions connected with the adipose organ. They are also involved in tumor development in humans. CONCLUSION: If the hypothesis of the evolutionary origin of the adipose organ from the ancestral hereditary tumor is correct, it may open new opportunities to resolve the oncological problem and the problem of the obesity epidemic. New interventions targeting LEP, NOTCH1, SPRY1, PPARG, ID2, and CIDEA gene network, in addition to what already is going on, can be designed for treatment and prevention of both obesity and tumors.

The Toxic Influence of Excess Free Iron on Red Blood Cells in the Biophysical Experiment: An In Vitro Study.

Iron is needed for life-essential processes, but free iron overload causes dangerous clinical consequences. The study of the role of red blood cells (RBCs) in the influence of excess free iron in the blood on the pathological consequences in an organism is relevant. Here, in a direct biophysical experiment in vitro, we studied the action of free iron overload on the packed red blood cell (pRBC) characteristics. In experiments, we incubated pRBCs with the ferrous sulfate solution (Fe2+). Wе used free iron in a wide range of concentrations. High Fe2+ concentrations made us possible to establish the pattern of the toxic effect of excess iron on pRBCs during a reduced incubation time in a biophysical experiment in vitro. It was found that excess free iron causes changes in pRBC morphology, the appearance of bridges between cells, and the formation of clots, increasing the membrane stiffness and methemoglobin concentration. We created a kinetic model of changes in the hemoglobin derivatives. The complex of simultaneous distortions of pRBCs established in our experiments can be taken into account when studying the mechanism of the toxic influence of excess free iron in the blood on pathological changes in an organism.