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The changes in lipid composition and phospholipase activity in damaged somatic nerves were studied against the background of the action of potassium hyaluronate and insulin-like growth factor-1. It has been shown that nerve cutting is accompanied by an increase in phospholipase A2 activity, resulting in an accumulation of lysophospholipids and free fatty acids, as well as an increase in phosphatidylinositol levels and a decrease in diacylglycerol content, which is most likely due to inactivation of phosphoinositide-specifi c phospholipase C against the background of injury to the nerve conductor. The introduction of potassium hyaluronate and insulin-like growth factor-1 enhances the recovery processes in the injured nerve conductor, however, the mechanisms of their action remain diff erent. According to the literature data and the results of our own research, the action of potassium hyaluronate and insulin-like growth factor-1 is realized as a result of the launch of signaling pathways associated with the regulation of the activity of enzymes from the phospholipase family. At the same time, our data on a decrease in the activity of phospholipase A2 and the absence of signifi cant changes in the level of phosphatidylinositol and diacylglycerol indicate that potassium hyaluronate most likely exerts its eff ect through the PL A2 -mediated pathway. In addition, it was shown that against the background of the action of IGF-1, an intensifi cation of phosphoinositide metabolism is observed, which is explained by the activation of phosphoinositidespecifi c phospholipase C. According to the literature, the launch of the phospholipase C-mediated mechanism is accompanied by the formation of components of the phosphatidylinositol 3-kinase signaling pathway involved in stimulation of the expression of various transcription factors necessary for axonal regeneration and restoration of the functioning of injured nerve conductors.

Background. The study of morphometric variability of the sella turcica and pituitary gland in individuals with different types of skull base is of theoretical importance and remains relevant in practical medicine for the diagnosis of pathological processes and the development of new methods of surgical intervention. The purpose of the research is to study the typical variability of the linear characteristics of the sella turcica, pituitary gland and their relationship according to MRI data. Materials and methods. The object of the study was 100 magnetic resonance imaging of the brain of men and women of the 1st and 2nd periods of adulthood, divided according to the size of the basilar angle into three craniotypes: flexi-, medio- and platybasilar. The dimensional characteristics of the sella turcica and pituitary gland were studied using the digital craniometry method, and a statistical analysis of the data obtained was carried out. Results. With an increase in the values of the basilar angle of the skull base from the flexibasilar type to the platybasilar type, a change in the linear parameters of both the sella turcica and the pituitary gland occurs. In the sella turcica, the length and width increase by 6.9% and 13.6%, respectively, while the height decreases by 13.0% (p < 0.05). The pituitary gland is characterized by a statistically significant increase in its length by 19.5% and width by 11.2% (p < 0.05), while the height of the gland does not change. Correlation analysis revealed relationships of different strength and direction between the longitudinal and latitudinal parameters of the sella turcica and the pituitary gland. Conclusions. The angle of the skull base (craniotype) affects the anatomical characteristics of the sella turcica and pituitary gland, as well as their relationship.

Nearly identical, repetitive elements in the genome contribute to the variability in genetic inheritance patterns, particularly in regions like the RCCX locus, where such repeats can lead to structural variations. In addition, during the formation of gametes as a result of meiosis, variants of loci with repetitive elements that do not code for the required proteins may occur. As a result, an individual with certain genetic rearrangements in this region may have an increased risk of developing a congenital disorder, particularly in cases where the non-functional allele is inherited dominantly. At the same time, there is still no routine or generally recognized diagnostic method to determine the sequence of the repetitive fragments. The functionally important RCCX locus consists of such repetitive fragments. The available knowledge about the genomic variants of the RCCX locus is fragmented, as there is no standardized method to determine its structure. It should be noted that in some structural variants of the RCCX locus, the sequence of protein-coding genes is disrupted, leading to the development of diseases such as congenital adrenal hyperplasia (CAH). Although genetic testing is generally accepted as a gold standard for CAH diagnosis, there are a myriad of strategies on which exact methods to use and in which order. The reason for this inconsistency lies in the complexity of the RCCX locus and the fact that each patient or carrier may have a highly individualized mutation or combination thereof. In this review, we have discussed all known methods that can be used to study the structure of the RCCX locus. As a result, optimal approaches are proposed for the diagnosis of the most common disease caused by lesions in the RCCX–CAH due to CYP21A2 deficiency.

Single-nucleotide polymorphisms (SNPs) can serve as reliable markers in genetic engineering, selection, screening examinations, and other fields of science, medicine, and manufacturing. Whole-genome sequencing and genotyping by sequencing can detect SNPs with high specificity and identify novel variants. Nonetheless, in situations where the interest of researchers is individual specific loci, these methods become redundant, and their cost, the proportion of false positive and false negative results, and labor costs for sample preparation and analysis do not justify their use. Accordingly, accurate and rapid methods for genotyping individual alleles are still in demand, especially for verification of candidate polymorphisms in analyses of association with a given phenotype. One of these techniques is genotyping using TaqMan allele-specific probes (TaqMan dual labeled probes). The method consists of real-time PCR with a pair of primers and two oligonucleotide probes that are complementary to a sequence near a given locus in such a way that one probe is complementary to the wild-type allele, and the other to a mutant one. Advantages of this approach are its specificity, sensitivity, low cost, and quick results. It makes it possible to distinguish alleles in a genome with high accuracy without additional manipulations with DNA samples or PCR products; hence the popularity of this method in genetic association studies in molecular genetics and medicine. Due to advancements in technologies for the synthesis of oligonucleotides and improvements in techniques for designing primers and probes, we can expect expansion of the possibilities of this approach in terms of the diagnosis of hereditary diseases. In this article, we discuss in detail basic principles of the method, the processes that influence the result of genotyping, criteria for selecting optimal primers and probes, and the use of locked nucleic acid modifications in oligonucleotides as well as provide a protocol for the selection of primers and probes and for PCR by means of rs11121704 as an example. We hope that the presented protocol will allow research groups to independently design their own effective assays for testing for polymorphisms of interest.

Background. The widespread use of functional endoscopic intervention in the nasal cavity requires detailed knowledge of the variant anatomy of the structures of the paranasal sinuses, taking into account age and gender, necessary to improve surgical treatment. In order to determine the variants of the structure of the anastomosis and intra-sinus septa of the maxillary sinus in childhood, a study was conducted of 425 computed tomograms of the heads of children aged 1 to 21 years of both sexes without pathology of the paranasal sinuses. Results and conclusions. It has been established that, regardless of gender, the width of the anastomosis of the maxillary sinus increases in each subsequent age group, with the largest increase at 2–3 years and 8–12 years and has no bilateral or gender differences. Intra- sinus bone septa in the first and second childhood ages were determined only in girls. In adolescence and adolescence - in persons of both sexes, and the frequency of occurrence increases with age in boys and young men. In the right maxillary sinus, incomplete and complete septa were identified, in the left - only incomplete. The greatest number of septa was observed in adolescence on the right. Intra-sinus septa can divide the sinus into two or more chambers of varying sizes, which remain connected to each other, creating difficulties during surgery. Thus, variants of the anatomical structure of the intra- sinus septa in children have been identified, associated with gender, age and side of the skull, while the variability of the width of the anastomosis depends only on age.

The research deals with estimating the potential of Russian enterprises of tube industry and possibilities of their efficient adaptation to fast changes. Academic results of the research include systematization, summarizing and author’s appraisal of processes taking place in Russian tube industry, as well as proposals aimed at its development. According to the research, Russian tube industry rather quickly adapts to changes and is still stable in spite of difficult situation and high sectoral risks. Today the potential of the increase in home demand for tubes is not realized in full, especially for products with high added value. Tube industry is facing the problem of importsubstitution in equipment purchase and production modernization. To resolve it a set of measures is necessary, such as starting the mechanism of innovation development in machine-building manufacturing; working-out the program of developing home industry of electronics, software, systems of management and engineering; motivating the growth in production capacities of machine-building enterprises. It is necessary to raise investment from countries importing tube products in Asia, Africa and Middle East. These regions can become both the marketing targets and sources of investment. In conditions of instability tube industry is strategically important for the country and needs measures of state support.

Purpose: to analyze intraocular fluid (IOF) cytokine concentrations in patients with diabetic macular edema (DME) after intravitreal therapy with angiogenesis inhibitors or corticosteroids (CS).Materials and methods. 44 patients (45 eyes) were divided in 2 groups depending on the therapy: group 1 (n = 19) received an angiogenesis inhibitor (aflibercept) while group2 (n = 26) received CS (dexamethasone implant). They were tested for IOF cytokine levels by Milliplex® Map Human Cytokine/Chemokine Panel at treatment start and 3 months after either 3 monthly injections of aflibercept or a single dexamethasone implant injection.Results. The concentrations of ten cytokines (IL-8/CXCL8, IP-10/CXCL10, MCP-1/CCL2, PDGF-AA, GROα/CXCL1, VEGF-A, MIP-1β/CCL4, IL-15, IL-7, IL-6) were found to fall significantly in both groups of therapy. IL-6 and IL-5 levels showed the most significant drop as compared to other cytokines, with a more pronounced decrease in the aflibercept treatment group. In both groups, VEGF-A concentration showed a significant drop, and the share of the eyes that responded to the treatment was 94.7 % in the aflibercept therapy group and 96.2 % in in the dexamethasone implant group.Conclusion. The IOF concentration assessment of a number of pro-inflammatory cytokines/chemokines shows that both the anti-VEGF agent — aflibercept and CS — dexamethasone implant contribute to a decrease of inflammation which is observed 3 months after the start of treatment.

Purpose: to analyze the levels of cytokines in intraocular fluid (IF) and blood plasma of patients with diabetic macular edema (DME) previously untreated by intravitreal therapy before and after the therapy by angiogenesis inhibitor or a corticosteroid. Material and methods. We examined 90 people — 47 females (52.2 %) and 43 males (47.8 %), mean age 64.54 ± 11.30 years. Of these, 60 had DME, and 30 formed the control group. The levels of 41 cytokines/chemokines in IF were determined by Milliplex® Map Human Cytokine/ Chemokine Panel; while the concentration of IL-18, MCP-1/CCL2, EPO, IL-10, IL-4, IL-6, IL-8, IFNα, VEGF-A in blood plasma was measured by enzyme-linked immunosorbent assay kits (Vector-Best, Russia). Patients with DME received intravitreal injections of an angiogenesis inhibitor (aflibercept. 50 eyes) or a corticosteroid (dexamethasone implant, 30 eyes). Results. Significant differences were revealed in 10 cytokine concentrations between the DME patients and the control group. The concentrations of IL-7, IL-15 and MCP-1/CCL2 levels in IF of DME patients were, respectively, 20.5, 20.3, and 11.02 times higher, than in the control group (р ˂ 0.05). Besides, a pairwise comparison of cytokines concentrations in IF of patients from either treatment group with the controls demonstrated a statistically significant increase in GROα/CXCL1 level. The pairwise comparison also revealed significant differences between the control and the corticosteroid therapy for systemic concentrations of IL-18 (p = 0.017), MCP-1/CCL2 (p = 0.009) and VEGF-A (p = 0.016). Conclusion. A pronounced and significant increase of the levels of a number of cytokines (e.g., IL-7, IL-15. FRACTALKINE/CX3CL1) were only sparsely reported before or remained undetermined at all. Our results on systemic cytokines levels may serve as prerequisite for further research into the role of systemic inflammation in DME pathogenesis. The analysis of associations of our results with those of other clinical biomarkers will contribute to the development of individualized treatment strategies.

This paper delves into an interference analysis, focusing on the forthcoming Starlink Generation 2 satellites, stated to operate within the 1990–1995 MHz frequency band. The aim is to assess the potential interference from this Starlink system to the satellite receivers of mobile satellite systems (MSSs), which are set to function within the 1980–2010 MHz range, and satellite receivers of the NTN systems, which are planned to operate in the n256 bands, defined by the 3GPP specifications. Through simulation-based evaluations, both single-entry and aggregate interference levels from Starlink to MSSs and NTN systems are comprehensively explored. To estimate the interference impact, several protection criteria were used. The study is in line with the Recommendations of International Telecommunication Union (ITU-R) and common approaches that are used when performing compatibility studies between satellite systems. The findings of this study demonstrate the feasibility of utilizing the n25 band for NTN direct-to-device services.

The article studies key normative legal acts and laws that regulate the field of treating solid municipal waste (SMW) and functioning of regional operators on SMW treatment. It analyzes organization and economic problems of regional operators’ functioning. Key problems include the inability of regional committees on tariffs and prices to regulate regional operators due to the absence of the unified approach to such regulation; the complexity of identifying economically grounded expenses of regional operator; restrictions in methodological directions in articles of costs of container-bunker fleet; availability of big payable debt due to incomplete collection of pay for SMW treatment and so on. Special attention is paid to the problem connected with taking records of secondary resources and secondary raw materials from SMW. To solve this problem it was proposed to set up and develop the exchange of secondary resources, which could extend a set of organization and economic functions of regional operators dealing with SMW treatment and build new economic ties with enterprises within the frames of closed cycle economy.

Nearly identical, repetitive elements in the genome contribute to the variability in genetic inheritance patterns, particularly in regions like the RCCX locus, where such repeats can lead to structural variations. In addition, during the formation of gametes as a result of meiosis, variants of loci with repetitive elements that do not code for the required proteins may occur. As a result, an individual with certain genetic rearrangements in this region may have an increased risk of developing a congenital disorder, particularly in cases where the non-functional allele is inherited dominantly. At the same time, there is still no routine or generally recognized diagnostic method to determine the sequence of the repetitive fragments. The functionally important RCCX locus consists of such repetitive fragments. The available knowledge about the genomic variants of the RCCX locus is fragmented, as there is no standardized method to determine its structure. It should be noted that in some structural variants of the RCCX locus, the sequence of protein-coding genes is disrupted, leading to the development of diseases such as congenital adrenal hyperplasia (CAH). Although genetic testing is generally accepted as a gold standard for CAH diagnosis, there are a myriad of strategies on which exact methods to use and in which order. The reason for this inconsistency lies in the complexity of the RCCX locus and the fact that each patient or carrier may have a highly individualized mutation or combination thereof. In this review, we have discussed all known methods that can be used to study the structure of the RCCX locus. As a result, optimal approaches are proposed for the diagnosis of the most common disease caused by lesions in the RCCX–CAH due to CYP21A2 deficiency. [ABSTRACT FROM AUTHOR]

Background: Age-related macular degeneration (AMD) is the leading cause of late-onset blindness in elderly. The occurrence and development of AMD is a multifactorial complex process where autophagy plays an important role. The first-line drugs for neovascular AMD (nAMD) are inhibitors of VEGF, with up to 30% of patients having an incomplete response to treatment. Genetic factors may influence the response to anti-VEGF therapy and explain treatment outcome variability. We aimed to estimate the role of polymorphic markers of the MTOR (rs1064261, rs1057079, rs11121704, rs2295080), SQSTM1 (rs10277), ULK1 (rs11246867, rs3088051), MAP1LC3A (rs73105013) and ATG5 (rs573775) genes in the development of nAMD and the efficacy of anti-VEGF therapy response. Methods: Genotyping by allele-specific PCR was performed in 317 controls and 315 nAMD patients in the Russian population. Of them, 196 treatment-naive nAMD patients underwent three monthly intravitreal injections (IVIs) of aflibercept. Genotypic frequencies were compared with OCT markers of therapy effectiveness and best-corrected visual acuity (BCVA) measures. The main outcomes were the BCVA gain and decrease in central retinal thickness (CRT). Results: MTOR-rs1057079-C, MTOR-rs11121704-C and MTOR-rs2295080-G alleles were associated with an increased risk of nAMD. The BCVA was increased in 117 (59.7%) patients by 10 [5–20] letters, did not changed in 59 (30.1%), and was decreased in 20 (10.2%) patients. ULK1-rs3088051 was associated with BCVA change. Among patients with the TT and CT genotypes for ULK1-rs3088051, an improvement in visual acuity was noted in 67.6% and 53.8% of cases, while in patients with the CC genotype, an increase in BCVA was recorded in 37.5% of cases (p = 0.01). The decrease in CRT was associated with SQSTM1-rs10277 (p = 0.001): it was significantly higher in TT (93 [58–122] mkm) and CT (66 [30–105] mkm) carriers compared to the CC genotype (47 [24–68] mkm). Other SNPs did not show significant associations with the outcome of anti-VEGF treatment. Conclusions: MTOR gene polymorphisms are moderately associated with the risk of nAMD. SQSTM1-rs10277 and ULK1-rs3088051 may influence short-term response to intravitreal anti-VEGF treatment. The results suggest that autophagy could be a target for future drugs to overcome resistance to anti-VEGF therapy.

Valery Danilenko,1 Andrey Devyatkin,2 Mariya Marsova,1 Madina Shibilova,3 Rustem Ilyasov,1 Vladimir Shmyrev4 1Vavilov Institute of General Genetics, Russian Academy of Sciences, Moscow, Russia; 2Central Clinical Hospital with a Polyclinic CMP RF, Moscow, Russia; 3Polyclinic No. 1 CMP RF, Moscow, Russia; 4Central State Medical Academy CMP RF, Moscow, RussiaCorrespondence: Rustem Ilyasov Email apismell@hotmail.comAbstract: In the last decade, metagenomic studies have shown the key role of the gut microbiome in maintaining immune and neuroendocrine systems. Malfunction of the gut microbiome can induce inflammatory processes, oxidative stress, and cytokine storm. Dysfunction of the gut microbiome can be caused by short-term (virus infection and other infectious diseases) or long-term (environment, nutrition, and stress) factors. Here, we reviewed the inflammation and oxidative stress in neurodegenerative diseases and coronavirus infection (COVID-19). Here, we reviewed the renin–angiotensin–aldosterone system (RAAS) involved in the processes of formation of oxidative stress and inflammation in viral and neurodegenerative diseases. Moreover, the coronavirus uses ACE2 receptors of the RAAS to penetrate human cells. The coronavirus infection can be the trigger for neurodegenerative diseases by dysfunction of the RAAS. Pharmabiotics, postbiotics, and next-generation probiotics, are considered as a means to prevent oxidative stress, inflammatory processes, neurodegenerative and viral diseases through gut microbiome regulation.Keywords: renin–angiotensin–aldosterone system, gut microbiome, coronavirus infection, COVID-19, neurodegenerative diseases, inflammatory processes, oxidative stress, pharmabiotics, probiotics, postbiotics, symbiotics, Lactobacillus