[Pattern of biochemical markers of mineral and bone disorders in kidney transplant recipients: real-world data].

BACKGROUND: There is a lack of studies providing comprehensive data on the prevalence of mineral and bone disorders (MBD) laboratory abnormalities after kidney transplantation in Russia. AIM: to obtain real-world data on the prevalence of the main mineral abnormalities among kidney transplant recipients and to revise their concomitant MBD therapy. METHOD: This cross-sectional study included 236 patients with successful kidney transplantation. Their serum intact parathyroid hormone (iPTH), total calcium (Ca), phosphorus (P), and alkaline phosphatase (ALP) levels were measured. RESULTS: Only 6.2% of our cohort had all laboratory parameters within the target range, whereas persistent HPT along with hypercalcemia was noted in almost one third of the patients (31%). Normal iPTH levels were observed in 13% cases; 84% of the patients had hyperparathyroidism. The fraction of patients with target iPTH did not differ between the groups with normal and decreased estimated glomerular filtration rate (eGFR) (p=0.118). Hypercalcemia was observed in 29% cases. The serum P level varied significantly in groups with different eGFR (p<0.0001), increasing with declining graft function. Furthermore, 40.7% of patients had ALP above the target range. While 123 patients received active vitamin D (alfacalcidol), 33 received monotherapy with inactive vitamin D (cholecalciferol). The control group consisted of 57 medication-naïve patients. The serum total Ca level varied significantly between the groups (p=0.0006), being higher in patients supplemented with cholecalciferol. The fraction of patients with normocalcemia was lowest in the cholecalciferol group (chi-square, р=0.0018). CONCLUSION: The prevalence of biochemical abnormalities after kidney transplantation is high. Alfacalcidol usage may be safer than using cholecalciferol to prevent hypercalcemia development.

Relationship of the gene pool of the Khants with the peoples of Western Siberia, Cis-Urals and the Altai-Sayan Region according to the data on the polymorphism of autosomic locus and the Y-chromosome.

Khanty are indigenous Siberian people living on the territory of Western Siberia, mainly on the territory of the Khanty-Mansiysk and Yamalo-Nenets Autonomous Okrugs. The present study is aimed at a comprehensive analysis of the structure of the Khanty gene pool and their comparison with other populations of the indigenous population of Southern and Western Siberia. To address the issues of genetic proximity of the Khanty with other indigenous peoples, we performed genotyping of a wide genomic set of autosomal markers using high-density biochips, as well as an expanded set of SNP and STR markers of the Y-chromosome in various ethnic groups: Khakas, Tuvans, Southern Altaians, Siberian Tatars, Chulyms (Turkic language family) and Kets (Yeniseian language family). The structure of the gene pool of the Khanty and other West Siberian and South Siberian populations was studied using a genome-wide panel of autosomal single nucleotide polymorphic markers and Y-chromosome markers. The results of the analysis of autosomal SNPs frequencies by various methods, the similarities in the composition of the Y-chromosome haplogroups and YSTR haplotypes indicate that the Khanty gene pool is quite specific. When analyzing autosomal SNPs, the Ugrian genetic component completely dominates in both samples (up to 99-100 %). The samples of the Khanty showed the maximum match in IBD blocks with each other, with a sample of the Kets, Chulyms, Tuvans, Tomsk Tatars, Khakas, Kachins, and Southern Altaians. The degree of coincidence of IBD blocks between the Khanty, Kets, and Tomsk Tatars is consistent with the results of the distribution of allele frequencies and common genetic components in these populations. According to the composition of the Y-chromosome haplogroups, the two samples of the Khanty differ significantly from each other. A detailed phylogenetic analysis of various Y-chromosome haplogroups made it possible to describe and clarify the differences in the phylogeny and structure of individual ethnospecific sublines, to determine their relationship, traces of population expansion in the Khanty gene pool. Variants of different haplogroups of the Y-chromosome in the Khanty, Khakas and Tuvans go back to their common ancestral lines. The results of a comparative analysis of male samples indicate a close genetic relationship between the Khanty and Nenets, Komi, Udmurts and Kets. The specificity of haplotypes, the discovery of various terminal SNPs confirms that the Khanty did not come into contact with other ethnic groups for a long time, except for the Nenets, which included many Khanty clans.

Molecular genetic basis of epidermolysis bullosa.

Epidermolysis bullosa (EB) is an inherited disorder of skin fragility, caused by mutations in a large number of genes associated with skin integrity and dermal-epidermal adhesion. Skin fragility is manifested by a decrease in resistance to external mechanical influences, the clinical signs of which are the formation of blisters, erosions and wounds on the skin and mucous membranes. EB is a multisystemic disease and characterized by a wide phenotypic spectrum with extracutaneous complications in severe types, besides the skin and mucous membranes, with high mortality. More than 30 clinical subtypes have been identified, which are grouped into four main types: simplex EB, junctional EB, dystrophic EB and Kindler syndrome. To date, pathogenic variants in 16 different genes are associated with EB and encode proteins that are part of the skin anchoring structures or are signaling proteins. Genetic mutations cause dysfunction of cellular structures, differentiation, proliferation and apoptosis of cells, leading to mechanical instability of the skin. The formation of reduced proteins or decrease in their level leads mainly to functional disorders, forming mild or intermediate severe phenotypes. Absent protein expression is a result of null genetic variants and leads to structural abnormalities, causing a severe clinical phenotype. For most of the genes involved in the pathogenesis of EB, certain relationships have been established between the type and position of genetic variant and the severity of the clinical manifestations of the disease. Establishing an accurate diagnosis depends on the correlation of clinical, genealogical and immunohistological data in combination with molecular genetic testing. In general, the study of clinical, genetic and ultrastructural changes in EB has significantly expanded the understanding of the natural history of the disease and supplemented the data on genotype-phenotype correlations, promotes the search and study of epigenetic and non-genetic disease modifier factors, and also allows developing approaches to radical treatment of the disease. New advances of sequencing technologies have made it possible to describe new phenotypes and study their genetic and molecular mechanisms. This article describes the pathogenetic aspects and genes that cause main and rare syndromic subtypes of EB.

Structure and origin of Tuvan gene pool according to autosome SNP and Y-chromosome haplogroups.

Tuvans are one of the most compactly living peoples of Southern Siberia, settled mainly in the territory of Tuva. The gene pool of the Tuvans is quite isolated, due to endogamy and a very low frequency of interethnic marriages. The structure of the gene pool of the Tuvans and other Siberian populations was studied using a genome-wide panel of autosomal single nucleotide polymorphic markers and Y-chromosome markers. The results of the analysis of the frequencies of autosomal SNPs by various methods, the similarities in the composition of the Y-chromosome haplogroups and YSTR haplotypes show that the gene pool of the Tuvans is very heterogeneous in terms of the composition of genetic components. It includes the ancient autochthonous Yeniseian component, which dominates among the Chulym Turks and Kets, the East Siberian component, which prevails among the Yakuts and Evenks, and the Far Eastern component, the frequency of which is maximum among the Nivkhs and Udeges. Analysis of the composition of IBD-blocks on autosomes shows the maximum genetic relationship of the Tuvans with the Southern Altaians, Khakas and Shors, who were formed during the settlement of the Turkic groups of populations on the territory of the Altai-Sayan region. A very diverse composition of the Tuvan gene pool is shown for various sublines of Y-chromosomal haplogroups, most of which show strong ethnic specificity. Phylogenetic analysis of individual Y-chromosome haplogroups demonstrates the maximum proximity of the gene pool of the Tuvans with the Altaians, Khakas and Shors. Differences in frequencies of Y-chromosome haplogroups between the Todzhans and Tuvans and a change in the frequencies of haplogroups from south to north associated with the East Asian component were found. The majority of the most frequent Y-chromosome haplogroups in the Tuvans demonstrate the founder effect, the formation age of which is fully consistent with the data on their ethnogenesis.

Blocks identical by descent in the genomes of the indigenous population of Siberia demonstrate genetic links between populations.

The gene pool of the indigenous population of Siberia is a unique system for studying population and evolutionary genetic processes, analyzing genetic diversity, and reconstructing the genetic history of populations. High ethnic diversity is a feature of Siberia, as one of the regions of the peripheral settlement of modern human. The vast expanses of this region and the small number of aboriginal populations contributed to the formation of significant territorial and genetic subdivision. About 40 indigenous peoples are settled on the territory of the Siberian historical and ethnographic province. Within the framework of this work, a large-scale population study of the gene pool of the indigenous peoples of Siberia was carried out for the first time at the level of high-density biochips. This makes it possible to fill in a significant gap in the genogeographic picture of the Eurasian population. For this, DNA fragments were analyzed, which had been inherited without recombination by each pair of individuals from their recent common ancestor, that is, segments (blocks) identical by descent (IBD). The distribution of IBD blocks in the populations of Siberia is in good agreement with the geographical proximity of the populations and their linguistic affiliation. Among the Siberian populations, the Chukchi, Koryaks, and Nivkhs form a separate cluster from the main Siberian group, with the Chukchi and Koryaks being more closely related. Separate subclusters of Evenks and Yakuts, Kets and Chulyms are formed within the Siberian cluster. Analysis of SNPs that fell into more IBD segments of the analyzed populations made it possible to compile a list of 5358 genes. According to the calculation results, biological processes enriched with these genes are associated with the detection of a chemical stimulus involved in the sensory perception of smell. Enriched for the genes found, molecular pathways are associated with the metabolism of linoleic, arachidonic, tyrosic acids and by olfactory transduction. At the same time, an analysis of the literature data showed that some of the selected genes, which were found in a larger number of IBD blocks in several populations at once, can play a role in genetic adaptation to environmental factors.

Society and the State in Russia and the World during the Coronavirus Epidemic.

This article is based on a report presented at the Scientific Session of the RAS General Meeting (Moscow, December 15, 2021). The reaction of society to the pandemic in Russia and other countries of the world is analyzed from an anthropological point of view. The features of the behavior and psychological reaction of residents of different regions, professional groups, and ethnocultural communities are considered with account for gender, age, and cultural characteristics (collectivism‒individualism, looseness‒tightness, power distance). Particular attention is paid to phobias and social activity during the pandemic; the growing role of nation-states in overcoming the consequences of the pandemic is discussed. The results presented can be used as an additional source of information for taking effective measures finally to overcome the pandemic and, most importantly, its negative social and political consequences.

[Mathematical modeling of high-flow extra-intracranial bypass in the treatment of a complex cerebral aneurysm]. / Matematicheskoe modelirovanie obkhodnogo vysokopotochnogo ekstra-intrakranial'nogo shuntirovaniya pri lechenii slozhnoi tserebral'noi anevrizmy.

BACKGROUND: Intracranial aneurysms (IAs) pose a high risk of spontaneous subarachnoid hemorrhage. In the most complex cases, the only way to exclude the aneurysm from the circulation is to perform a high-flow extracranial-to-intracranial bypass, thus creating a new bloodstream. This avoids severe ischemic complications; however, it requires careful consideration of individual anatomy and hemodynamic parameters. Computational fluid dynamics (CFD) can be of great help in planning such a surgery by creating 3D patient-specific models of cerebral circulation. OBJECTIVE: Assessment of the perspectivity of high-flow extracranial-to-intracranial bypass planning using computational modeling. MATERIAL AND METHODS: In this research work, we have applied the CFD methods to a patient with a giant thrombosed IA of the internal carotid artery (ICA). Preoperative CTA images and Gamma Multivox workstation were used to create a 3D model with current geometry and three additional models: Normal anatomy (no IA), Occlusion (with ligated ICA), Virtual bypass (with bypass and ligated ICA). The postoperative data were also available. Boundary conditions were based on PC-MRI measurements. Calculation of hemodynamics was conducted with a finite element package ANSYS Workbench 19. RESULTS: The results demonstrated an increase in the blood flow on the affected side by more than 70% after the virtual surgery and uniformity of flow distribution between the affected and contralateral sides, indicating that the treatment is likely to be efficient. Later, postoperative data confirmed that. CONCLUSION: The study showed that virtual preoperative CFD modeling could significantly simplify and improve surgical planning.

[Protocol of Transcriptome Analysis of Decidual Placenta Cells].

The advent of high-throughput sequencing technologies has expanded our understanding of the biological significance of non-coding regions of the genome. In recent years, more and more studies have been devoted to studying the role of noncoding RNAs in the development of diseases, as well as their participation in various cellular processes. Until now, all transcriptome studies of native placental tissue with the description of the noncoding RNA region were carried out without isolating individual cell populations. This approach, due to the high cellular heterogeneity of the placental tissue, significantly complicates the ability to determine the molecular-biological functions of individual cells and their role in the molecular pathogenesis of reproductive disorders. In this work, we propose a technique for obtaining total RNA from single decidual cells of frozen placental tissue obtained by laser-capture microdissection technology for transcriptome sequencing, including a cluster of noncoding RNAs. This technique can be successfully used to study the full-genome expression profile of other placental cell populations. The high accuracy of results on the transcriptome profiling of decidual cells obtained using the developed technique was additionally confirmed by an integrative analysis with the results of a 10x Genomics experiment.

[Urethral microbiota in healthy men and patients with urethritis].

Non-gonococcal urethritis (NGU) is a common disease in men. The main cause of NGU is sexually transmitted infections, which can cause various complications, including reproductive ones. Chlamydia trachomatis and Mycoplasma genitalium are the most common causes of NGU, but no known viral or bacterial pathogens are detected in 28-50% of cases. Traditional research methods revealed a higher load of specific pathogens in patients with urethritis compared to the control, but these studies do not allow us to determine the total bacterial load in the urethra. Using the 16S rRNA sequencing method to characterize the urine and urethral microbiota reveals a diverse bacterial microbiota in both asymptomatic men and patients with NGU, which has a high diversity. The revealed microbiota in both healthy and patients with urethritis still has an ambiguous interpretation and requires further study.

[Natural Selection as a Driver for the Genetic Component of Preeclampsia].

Preeclampsia (PE) is a severe hypertensive pathology and affects 2-8% of pregnancies worldwide. Its etiopathogenesis is poorly understood, and prognostic biomarkers and effective treatments are unavailable for this pregnancy complication, determining the high rates of maternal and perinatal morbidity and mortality. Racial and ethnic differences in PE incidence are of interest to study in terms of evolutionary medicine because such variability can be considered as a side effect of adaptive changes that have occurred in the genetic structure of modern populations since the dispersal of Homo sapiens from Africa. Genetic diversity at 10 regulatory single nucleotide polymorphisms (rSNPs) associated with PE was studied in North Eurasian populations and world populations of the 1000 Genomes Project. The role of natural selection in the formation of this genetic diversity was assessed at the microevolutionary level. High interpopulation diversity was observed with the greatest contribution being made by allele frequencies of NDRG1 rs3802252 (FST = 0.157). Signatures of natural selection were detected for rs10423795 of LHB, rs2167270 of LEP, rs2227262 and rs3802252 of NDRG1, rs56153523 and rs8109071 of SYDE1, and rs72959687 of INHA. The results are consistent with two evolutionary hypotheses of PE, namely, those of ancestral susceptibility and genetic conflicts.

Exchange-bias and magnetic anisotropy fields in core-shell ferrite nanoparticles.

Exchange bias properties of MnFe[Formula: see text]O[Formula: see text]@[Formula: see text]-Fe[Formula: see text]O[Formula: see text] core-shell nanoparticles are investigated. The measured field and temperature dependencies of the magnetization point out a well-ordered ferrimagnetic core surrounded by a layer with spin glass-like arrangement. Quasi-static SQUID magnetization measurements are presented along with high-amplitude pulse ones and are cross-analyzed by comparison against ferromagnetic resonance experiments at 9 GHz. These measurements allow one to discern three types of magnetic anisotropies affecting the dynamics of the magnetic moment of the well-ordered ferrimagnetic NP's core viz. the easy-axis (uniaxial) anisotropy, the unidirectional exchange-bias anisotropy and the rotatable anisotropy. The uniaxial anisotropy originates from the structural core-shell interface. The unidirectional exchange-bias anisotropy is associated with the spin-coupling at the ferrimagnetic/spin glass-like interface; it is observable only at low temperatures after a field-cooling process. The rotatable anisotropy is caused by partially-pinned spins at the core/shell interface; it manifests itself as an intrinsic field always parallel to the external applied magnetic field. The whole set of experimental results is interpreted in the framework of superparamagnetic theory, i.e., essentially taking into account the effect of thermal fluctuations on the magnetic moment of the particle core. In particular, it is found that the rotatable anisotropy of our system is of a uniaxial type.

[Features of balloon angioplasty in the treatment of central vein stenosis in patients with arteriovenous fistula on programmed hemodialysis]. / Osobennosti primeneniya ballonnoi angioplastiki pri lechenii stenozov tsentral'nykh ven u bol'nykh s arteriovenoznoi fistuloi, poluchayushchikh lechenie programmnym gemodializom.

OBJECTIVE: To analyze AVF patency rates after balloon angioplasty and palliative open surgery in patients with native AVF and central vein stenosis. MATERIAL AND METHODS: The study included 39 patients who underwent percutaneous balloon angioplasty (main group) and 41 patients who underwent palliative interventions (comparison group): thrombectomy, proximalization of arteriovenous anastomosis, AVF blood flow reduction. All patients were diagnosed with stenosis of subclavian vein, innominate vein, inferior vena cava or multiple lesions. RESULTS: Primary annual patency rate in the main group was 15.4% [95% CI 6.2; 28.3], in the comparison group - 0% (p=0.0011). Secondary annual patency rate was 66.7% [95% CI 49.6; 79.1] and 19.5% [95% CI 9.2; 32.7], respectively (p<0.0001). In the main group, a strong negative correlation between primary patency rate and stenosis-free period was revealed (r= -0.627 [95%CI -0.787; -0.388], p<0.0001). We did not find such correlation in the comparison group (r=0,049 [95% CI -0.262; 0.351], p=0.7599). Thus, balloon angioplasty is less effective for delayed stenosis. This feature should be considered in planning vascular approach. Different primary and secondary patency rates in the comparison group indicate that AVF blood flow reduction is an effective palliative treatment. CONCLUSION: Balloon angioplasty can significantly increase duration of AVF patency. Effectiveness of this procedure significantly depends on the period of manifestation of central vein stenosis. Balloon angioplasty cannot be considered a radical method in case of significant stenosis. This method only prolongs period for creation of new permanent contralateral vascular approach. Reduction of AVF blood flow can significantly reduce clinical severity of central vein stenosis and slightly extends the period of AVF patency.

Sporadic increases of radioactive aerosols as a possible reason for heavy nuclides enhancements recorded with the en-detectors.

Some unexpected sporadic increases of an environmental radioactive background have been recorded at mountain level at Baksan Neutrino Observatory (BNO, 1700 m above sea level) using electron-neutron detectors (en-detectors), which could be explained by radioactive aerosol enhancements. The large area inorganic scintillator en-detectors developed for cosmic ray study are continuously monitoring environmental thermal neutron fluxes at various geophysical conditions. Application of the pulse shape discrimination method allows us to select and separately measure both thermal neutrons and radioactive beta-decay nuclides being products of radon decays in air (mostly Rn-222 and Rn-220). There are two en-detector setups running now at BNO, one deep underground while another one at surface. Both installations had recorded some strange sporadic increases of radioactive nuclides in air. In this paper, we present results and the most probable explanation of the significant increases joint by radioactive aerosols production but caused by different reasons: Baksan river floods or nearby underground experiment with powerful Cr-51 radioactive source.

[The Role of Natural Selection in the Formation of the Genetic Structure of Populations by SNP Markers in Association with Body Mass Index and Obesity].

Obesity is one of the major challenges in modern society. More than a third of the world's population suffers froms overweight. This phenotype affects the quality of life and is associated with cardiovascular diseases, diabetes, cancer and reproductive disorders. The population variability of allele frequencies of 26 single nucleotide polymorphisms, in association with obesity and body mass index, according to data from genome-wide association studies (GWASs) is discussed in this study. Genetic variability was analyzed in populations of Northern Eurasia and populations from the human genome diversity project (HGDP). The population samples are characterized by high genetic diversity that correlates with climatic and geographical parameters. The results of the test for searching for natural selection signals revealed a selection effect for rs1167827 of the HIP1 gene, rs7138803 and rs7164727 located in the intergenic region, rs7141420 of the NRXN3 gene, rs7498665 of the SH2B1 gene, and rs7903146 of the TCF7L2 gene.

[Microbiota of the urogenital organs].

A review of modern literature on the study of microbiota of the genitourinary system by methods of chromatography-mass spectrometry and sequencing of urine specimens is presented in the article. The sequencing method is used to analyze microbiota of different organs. Obtained results of the genomic analysis have revealed cases of infection by potential pathogenic microorganisms, which are often not diagnosed during standard urine culture due to specific requirements for culture media.

[Difficulties in diagnosis of dislocated permanent dialysis catheter followed by perforation of right internal jugular and massive hemothorax]. / Trudnosti diagnostiki dislotsirovannogo permanentnogo dializnogo katetera, privedshei k massivnomu gemotoraksu pri perforatsii pravoi vnutrennei iaremnoi veny.

Great vein perforation followed by massive hemothorax occurred after implantation of permanent dialysis catheter. Diagnostic difficulties in this case were caused by placement of catheter's shadow in the projection of right atrium on the frontal X-ray scan. Injury of initial segment of superior vena cava was diagnosed during emergency surgery for ongoing bleeding.

The interaction effect of angiogenesis and endothelial dysfunction-related gene variants increases the susceptibility of recurrent pregnancy loss.

PURPOSE: The role of genetic polymorphisms in the pathogenesis of recurrent pregnancy loss (RPL) has been studied intensively. Complex diseases, including miscarriage, are believed to have a polygenic basis, and gene-gene interactions can play a significant role in the etiology of the disease. This study was conducted to investigate the association of gene-gene interactions with angiogenesis, endothelial dysfunction-related gene polymorphisms, and RPL. METHODS: A case-control study was conducted with 253 unrelated RPL patients with 2 or more spontaneous pregnancy losses and 339 healthy women with no history of pregnancy complications. Genotyping of single-nucleotide polymorphisms (SNPs) was performed using real-time polymerase chain reaction (real-time PCR), restriction fragment length polymorphism (RFLP), or allele-specific polymerase chain reaction methods. RESULTS: The genotypes 677TT of the MTHFR gene, 936TT, 936CT, and 634CC, 634GC of the VEGF gene, and allele 894T of the NOS3 gene were associated with a predisposition to RPL in the Russian population. A significant role of additive and epistatic effects in the gene-gene interactions of the SNPs of SERPINE-1, ACE, NOS3, MTHFR, and VEGF genes in RPL was demonstrated. CONCLUSIONS: The results showed that gene-gene interactions are important for RPL susceptibility. Additionally, analysis of the genotype combinations of several allelic variants provides more information on RPL risk than analysis of independent polymorphic markers.

[A rare variant in the sortilin-related receptor 1 gene is associated with declined cognitive functions in the elderly]. / Redkii variant v gene sortilinpodobnogo retseptora 1: sviaz' s pokazateliami kognitivnykh funktsii u pozhilykh.

AIM: To estimate the association of rs11218343 in the sortilin-related receptor 1 (SORL1) gene with cognitive performance in the elderly and with Alzheimer's disease (AD) in the Russian population. MATERIAL AND METHODS: A sample included 586 elderly people (mean age 70.9±5.7 years) without AD diagnosis and 100 patients with late-onset AD (mean age 72.1±7.8 years) from the Tomsk population. SORL1 rs11218343 was genotyped using PCR and MALDI-TOF mass spectrometry. Cognitive performance in the sample of elderly without AD was assessed by Montreal Cognitive Assessment (MoCA) test. RESULTS: Allele frequencies of the SORL1 polymorphism were not significantly different between the elderly without AD and AD patients. However mean MoCA score in the carriers of the rare allele (19.00±6.61) was significantly lower than in homozygotes for the common variant (22.25±3.89) (F=4.97; p=0.026). CONCLUSION: The rare variant in SORL1 gene previously associated with AD in genome-wide association studies and meta-analyses was associated with lower total МоСА scores in the random sample of elderly people that suggests declined cognitive functions in the carriers of this variant in elderly.

Quadrupole mass filter acceptance in stability island created by double-frequency quadrupole excitation.

Increase in quadrupole mass filter resolution at separation in narrow band stability island (X-band) formed by biharmonic resonance excitation of ion oscillation is discussed. X-band and the normal working quadrupole mass filter modes are compared at theoretical resolution of 10,000 and different separation times. Transmission curves, acceptance ellipses parameters, and acceptance characteristics are obtained by numerical simulation. Transmission coefficients are approximately the same in both modes. Dependence of acceptance ellipses parameters on ion inlet phases has a complicated oscillating form in the X-band mode. Acceptance contours calculated for given transition levels have been compared. At low acceptance level, the combined acceptance in the X-band mode was found to be one order of magnitude higher than in the normal mode.