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Digital transformation of document arrays has changed the nature of information infrastructure, as the digital documents are created, distributed, discovered and delivered in principally other way than in the epoch of printed matters as the main information media. The transition to digital information infrastructure has resulted in the loss of role of libraries as an essential intermediate on the document author-to-reader way, reasonably displacing libraries to the periphery of information activities and depreciating the majority of methods and technologies of document array organization developed through the centuries. The author substantiates the rationale for degrading information component of library mission and the necessity to transit to prevalent analytical services. The decreasing role of libraries is determined by the following factors: reduction of overall printed publications; their lower contextual value; capabilities to store, distribute, process digital information array formally and semantically, information deliver to users without the input of librarian. Therefore, not all the manual processing operations have become demanded any more. The print arrays grow scanty quantitively and contextually, and the increasing and dynamical digital flows are processed by ever-improving software. The author sees the solution in expanding analytical function of libraries which envisages inclusion of professional competences related to complex analytical processes, i. e. fact search and verification; acquisition and processing of statistical and experimental research data, preparation of analytical surveys, reviews and reports.

In this study, the association between maternal age at menarche (AAM)-related polymorphisms and offspring birth weight (BW) was studied. The work was performed on a sample of 716 pregnant women and their newborns. All pregnant women underwent genotyping of 50 SNPs of AAM candidate genes. Regression methods (linear and Model-Based Multifactor Dimensionality Reduction (MB-MDR)) with permutation procedures (the indicator pperm was calculated) were used to identify the correlation between SNPs and newborn weight (transformed BW values were analyzed) and in silico bioinformatic examination was applied to assess the intended functionality of BW-associated loci. Four AAM-related genetic variants were BW-associated including genes such as POMC (rs7589318) (βadditive = 0.202/pperm = 0.015), KDM3B (rs757647) (βrecessive = 0.323/pperm = 0.005), INHBA (rs1079866) (βadditive = 0.110/pperm = 0.014) and NKX2-1 (rs999460) (βrecessive = −0.176/pperm = 0.015). Ten BW-significant models of interSNPs interactions (pperm ≤ 0.001) were identified for 20 polymorphisms. SNPs rs7538038 KISS1, rs713586 RBJ, rs12324955 FTO and rs713586 RBJ–rs12324955 FTO two-locus interaction were included in the largest number of BW-associated models (30% models each). BW-associated AAM-linked 22 SNPs and 350 proxy loci were functionally related to 49 genes relevant to pathways such as the hormone biosynthesis/process and female/male gonad development. In conclusion, maternal AMM-related genes polymorphism is associated with the offspring BW.

The genetic diversity of sixteen native populations of North Eurasia is investigated using a panel of genetic markers in genes associated, according to the data of genome-wide association studies, with diseases that lead to impaired human cognitive functions (schizophrenia, Alzheimer’s disease, and their cognitive endophenotypes). There is a decrease in genetic diversity in the geographic space from west to east. The highest level of genetic diversity was shown in Caucasoid populations. There are two groups of SNPs that predominate in Caucasians or Mongoloids. The location of sixteen populations in the space of the principle components demonstrates their geographic localization. Clusterization of populations in accordance with their affiliation to four geographic regions was observed. In general, the analysis of within- and between-population genetic diversity for 28 markers in 16 populations replicates the patterns of the Northern Eurasia gene pool structure, which are described using other marker systems.

A replicative analysis of associations with obesity of 53 polymorphic markers associated with the results of genome-wide studies with variability of the body mass index and/or obesity was performed. For the first time in the Russian population, an association with obesity of polymorphic markers rs3810291 of the ZC3H4 gene, rs12940622 of the RPTOR locus, rs1800437 of the GIPR gene, and rs13021737 located in the intergenic region of the genome is shown. Possible molecular mechanisms for the involvement of the studied genes in the pathogenesis of the disease are discussed.

The review discusses the data on the significant role of pregnancy in adaptive evolution of modern humans. In the aspect of evolutionary medicine, the main attention is paid to preeclampsia (PE), a severe hypertensive pathology of pregnancy. The current evolutionary hypotheses about the origin and causes of racial and ethnic variability in the incidence of this pathology in human populations are summarized. Studies that suggest the contribution of adaptive evolution to the formation of a hereditary predisposition to the development of PE are presented. Our results which first showed the significant role of negative selection in the formation of the genetic architecture of PE via the regulatory single nucleotide polymorphisms of new candidate genes for this pathology are demonstrated.

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.

BACKGROUND AND AIMS We aimed to analyze the outcomes of HD patients with COVID-19 hospitalized in the Moscow region, Russia, and to compare it with those in the general population. METHOD Data were obtained retrospectively from the Moscow region COVID-19 register database, which comprises all hospitalizations with suspected or confirmed COVID-19 between February 2020 and November 2021. A total of 384 327 patients were included; 1 435 of them were ESRD patients. RESULTS Among ESRD patients there were 1386 HD patients and 49 kidney graft recipients. Thus, during the specified period, 48.5% of all prevalent HD patients of the Moscow region and only 7.8% of the graft recipients required hospitalization. Due to a few number of hospital admissions among kidney recipients they were excluded from the further analyses. We observed typical 4 waves of hospital admissions in the general population, but not in HD patients. In these patients, we noted a peak in December 2020 with a subsequent decrease in February, 2021; then the number of hospitalizations remained stable. The proportion of HD patients was approximately 0.5% of all patients with COVID-19 admitted to hospital. Almost all HD patients with COVID-19 were hospitalized regardless of disease severity. The mean age of hospitalized HD patients was significantly more than that in the general population: 68.95 ± 13.69 years versus 59.18 ± 17.11 years, P HD was associated with a significant increase in the risk of critical but stable and extremely critical (+ worsened: terminal and clinical death) condition at admission (Figure 1A): RR = 3.36 [95% confidence interval (95% CI) 3.12–3.59], P HD patients were significantly more likely to need for any kind of respiratory support (oxygen mask and mechanical ventilation (MV)) or MV alone (Figure 1B): RR = 1.72 (95% CI 1.63–1.81), P HD was associated with a significant increase in the risk of death (Figure 1C): RR = 3.48 (95% CI 3.24–3.72), P HD significantly increased the risk of death in patients without oxygen support and in patients with need for an oxygen mask (Figure 2A): RR = 3.56 (95% CI 2.97–4.25), P 95% in both cohorts: RR = 0.999 (95% CI 0.955–1.01), P = 0.309. Deceased patients were older than survivors both in HD patients [73 (IQR 65–82) versus 69 (IQR 59–78) years; P Heart and lung diseases increased the risk of death. In the general population concomitant heart diseases worsened the prognosis to a greater extent compared with lung diseases: RR = 2.69 (95% CI 2.64–2.74), P In the multivariate model, significant predictors of death in HD patients were need for MV (OR = 9.81, 95% CI 8.48–17.8; P CONCLUSION HD patients with COVID-19 have a significantly worse prognosis compared with the general population. The main risk factors for death are need for respiratory support and pre-existing lung diseases.

BACKGROUND AND AIMS Older adults are approximately 40% of all prevalent HD patients (ERA-EDTA Annual report, 2019). Cardiovascular disease is the leading cause of death in this cohort. It is well-known that the cardiotoxic effect of arterio-venous fistula (AVF) is fully realized when cardio-fistula recirculation (CFR) is above 20–30%. We believe that the reduction of AVF blood flow (Qa) in the elderly is often less effective than in younger patients. To evaluate the outcomes of Qa reduction in the elder and the younger HD patients. METHOD The prospective cohort study included 21 patients ˃ 60 years and 36 patients ˂60 years: the median age was 74 years [interquartile range (IQR) 69; 78, min-max 64–81] and 41 years (IQR 35; 45, min-max 31; 55), respectively. In all patients, glomerular filtration rate (GFR) before reduction was more than 25%: 32.8% (IQR 29.2; 35.1, min-max 27.3; 38.9) and 33% (IQR 31; 35.125, min-max 27.1; 39.3), respectively. Qa reduction was performed by banding of the para-anastomotic AVF segment with intraoperative control (Doppler ultrasonography) until reaching Qa of 1.5 L/min or less. RESULTS In all patients, we noted a significant (P In both elder and younger patients, we noted a significant decrease in CFR—Figure 1. However, after Qa reduction, only 5/21 elderly patients had CFR value less than 20%. Thus, 17/21 patients had CFR in the ‘gray zone’ —20–30%: 22.8% (IQR 21.85; 27.3, min-max 21; 29.2). In younger patients, 25/36 had CFR ˂ 20% after Qa reduction, while 11 stayed in the ‘gray zone’: 21.15% (IQR 20.575; 22.3, min-max 20.3; 23.4). The probability of reducing CFR to a safe level (˂ 20%) after surgery was significantly less in the elder patients: RR = 0.3429 [95% confidence interval (95%CI) 0.1495; 0.6852], P = 0.0011. We consider the lower baseline cardiac output in the elderly to be the main reason for the lower efficacy of Qa reduction: the difference between medians (older adults-younger patients before Qa reduction, Hodges–Lehmann method) was 1.9 L/min (95% CI 1.5; 2.4), P Moreover, the reduction of Qa in elderly patients led to a decrease in the ejection fraction (EF), which was not noticed in young patients—Figure 2. Notably, in all patients of both groups, the initial value of the EF was more than 55%. We believe that this can be explained by an abrupt increase in afterload against the background of a decreased compensatory heart capability in the elderly. At the same time, a decrease in the EF after Qa reduction in the elderly may indirectly indicate that conventional EF in the elderly is maintained by a presence of a high-flow AVF. Evaluation of EF against this background creates a putative picture of well-being and can mask the development of heart failure with reduced EF for a long time. CONCLUSION We noted a lower efficacy of Qa reduction as a method of reducing both cardio-fistula recirculation and cardiovascular risk in the elder patients compared to the younger patients on maintenance HD. Elder patients seem to require a different approach to reduce cardiovascular risk than younger patients.

BACKGROUND AND AIMS Cardiopulmonary recirculation (CRP) is one of the most informative instrumental parameters, widely used to predict adverse cardiovascular events in patients on maintenance hemodialysis (HD). CRP calculation is based on two indirectly measured estimates: AVF volume blood flow (Qa) and cardiac output (CO). Large CRP variability may cause underestimation of cardiovascular risk in many HD patients. We aimed to study the inter- and inner-observer agreement of Qa and CO. As a second step, we studied the changes in Qa, CO and CPR before and after HD. METHOD The prospective study included 88 patients with native AVF. At the first step, we evaluated the inter- and inner-observer agreement of Qa measurement with color duplex ultrasound (Bland–Altman plots, Figure 1A–D). Two specialists with 5–7 years of experience measured Qa twice on brachial artery, twice on fistula vein. To estimate the maximum relative error in paired measurements we calculated the mean and the absolute mean difference for each pair. Then, the absolute mean difference was divided by mean; the greatest deviations from the average are given in %. After that, they measured CO twice before HD and once after HD. Ultrafiltration during HD was 1.6 ± 0.34 L. RESULTS We observed a good concordance between Qa measurements on brachial artery by one specialist (Figure 1A) and by two specialists (Figure. 1B): deviations were [–13.9%; 13.1%] and [–18.3%; 16.4%], respectively. There was a poor concordance between assessments on brachial artery and fistula vein (Figure 1C), and Qa measurement on fistula vein alone (Figure 1 D). In the latter case, the variance was very high even if measurements were performed by one specialist: deviations were [–37.9%; 39.6%] and [–59.3%; 93.6%], respectively. In all cases, the systematic bias was low, but the deviations were significantly different between measurement methods. The variance of bias increased along with increasing of Qa. We observed a good concordance between CO assessments made by one specialist and between specialists: deviations were [–12.4%; 12.3%] and [–10.5%; 9.1%], respectively. The main pitfall of CPR-based cardiovascular risk stratification is that CO changes significantly after HD (Fig. 2A), while Qa values remain relatively stable (Figure 2B): although Qa difference before and after HD is statistically significant, it seems to be modest. Median CO decrease after HD was 13.4% (26.6% max), while median of Qa decrease was 1.7% (6.1% max). This leads to a significant increase of CPR value after HD, which can reach 40%(! ) in some patients (absolute increase of 0.11) (Figure. 2C). CPR value more than 30% is considered to be an indication for Qa reduction. In our cohort, 17% of the patients had CPR >30% before HD and 42% after HD. CONCLUSION Qa assessment should be performed only on brachial artery. There is a significant decrease in CO after HD even if ultrafiltration was moderate, whereas Qa remains relatively stable. This leads to a significant increase of CPR value in some patients after HD. CPR assessment before HD may lead to underestimation of cardiovascular risk. The decision on Qa reduction to decrease CPR should be based on CPR assessment after HD session.

BACKGROUND AND AIMS Patients on HD are known to have many various adverse events associated with past COVID-19. In this cross-sectional study, we assessed the incidence of vascular access (VA) dysfunction (primary end point) and probability of successful reconstruction of preexisting permanent VA (AVF/AVG) in a case of its dysfunction (secondary end point) within two months after discharge from COVID hospital. METHOD Data were obtained from Moscow region COVID-19 register database. The study includes the results of treatment of 1386 HD patients who were admitted to hospital with suspected or confirmed COVID-19 between February 2020 and November 2021. All COVID-19 positive patients were hospitalized regardless of disease severity to prevent further spread of the infection in dialysis units. The main analysis included 934 patients with known sustainable VA: AVF (N = 804, 86.3%), AVG (N = 54, 5.8%) or CVC (N = 74, 7.9%). Median duration of HD was 34 (IQR 21–69) months (from 6 to 98). RESULTS Hospital mortality among HD patients was 32.3%. The AVF/AVG/CVC ratio in recovered (N = 632) and deceased (N = 302) patients was 89.2%/5.7%/5% and 80.1%/6%/13.9%, respectively. HD via CVC was associated with an increased risk of death: RR = 1.877 (95% CI 1.472–2.302); P Most of the recovered patients with AVFs (Figure 1, left) and AVGs (Figure 1, right) needed interventions due the VA dysfunction. Even if AVF patency was successfully restored, it led to the reduction of its functional segment. In contrast, most of the recovered patients with CVCs did not receive interventions for VA dysfunction (Figure 2). Thus, only 45.4% (287 of 632) of recovered patients did not receive interventions for VA dysfunction; the rest 54.6% showed dysfunction of VA. 23.6% (N = 149) underwent successful AVF/AVG reconstruction and retained function of the preexisting VA. In 15.3% (N = 97) patients, AVF/AVG function was completely lost and a new AVF/AVG was created. Conversion from functional AVF/AVG into CVC was performed in 14.1% (N = 89) patients. Thus, the incidence of complete loss of preexisting permanent VA function was 29.4% (N = 186). Conversion into better vascular access was performed in only 1.7% (N = 11) patients: conversion from AVG into AVF or from CVC into AVF/AVG. Among patients who underwent successful reconstruction of preexisting AVF, the probability of successful restore of its function within the first month was 55.3% (95% CI 48.3–62.2), during the second month—only 31.1% (95% CI 22.9–40.4). For AVG, the probability of maintaining of existing access during the first and second months was 23.8% (95% CI 9.3–45.2] and 18.2% (95% CI 3.2–48.3), respectively. Thus, reconstruction of permanent VA within the second month after discharge from COVID hospital increases the risk of complete loss of its function: RR = 1.469 (95% CI 1.22–1.762). Only 6.6% (N = 37) of patients received AVF/AVG reconstruction in COVID hospital. Compared with 2019, in 2021 the rate of reconstructive surgeries in the Moscow region decreased from 2.771 (95% CI 2.426–3.15) to 1.375 (95% CI 1.114–1.68) per 10 patient-years (only prevalent HD patients; P At the same time, the rate of CVC implantations increased (outside of COVID hospitals) from 1.498 (95% CI 1.248–1.784) to 2.908 (95% CI 2.522–3.337) per 10 patient-years; P CONCLUSION COVID-19 is associated with high incidence of VA dysfunction and complete loss of VA function. The delay in reconstruction of existing VA significantly increases the risk of its loss. This may be caused by a decrease in the number of reconstructive VA surgeries due to reducing the number of specialized centers and personnel. As a result, we observe an increase in CVC usage. Thus, over the next few years, we can expect increased prevalence of central vein stenoses and deterioration of treatment outcomes of HD patients.

Here, we describe taxonomical composition, as well as seasonal and diel dynamics of airborne microbial communities in West Siberia. A total of 78 airborne biomass samples from 39 time intervals were analysed, within a temperature range of 48 °C (26 °C to - 22 °C). We observed a 5-170-fold decrease in DNA yield extracted from the airborne biomass in winter compared to summer, nevertheless, yielding sufficient material for metagenomic analysis. The airborne microbial communities included Actinobacteria and Proteobacteria, Ascomycota and Basidiomycota fungi as major components, as well as some Streptophyta plants. In summer, bacterial and fungal plant pathogens, and wood-rotting saprophytes were predominant. In winter, Ascomycota moulds and cold-related or stress environment bacterial species were enriched, while the fraction of wood-rotting and mushroom-forming Basidiomycota fungi was largely reduced. As recently reported for the tropical climate, the airborne microbial communities performed a diel cycle in summer, however, in winter diel dynamics were not observed. Ministry of Education (MOE) Published version This study was supported by Academic Research Fund (AcRF) Tier 3, Singapore Ministry of Education (grant number: MOE2013-T3-1-013). V.N.K and V.A.S were supported by the Russian Foundation of Basic Research (Project #18-29-13045). We thank Dr. Sharon Longford, Senior Assistant Director, Science Communications, Singapore Centre for Environmental Life Sciences Engineering (SCELSE), Nanyang Technological University for critical reading of this manuscript.

Haplotype associations of 894 DNA samples of elderly people from the Russian population of Tomsk were analyzed using 49 SNPs (single nucleotide polymorphisms). As the analyzed markers, SNPs were selected that showed an association with Alzheimer’s disease or variability of cognitive abilities in genome-wide association studies. As a result of the analysis, blocks on chromosomes 1, 2, 6, 8, 11, 19, and 20 were identified. Significant associations were shown, taking into account 50 000 permutations, for haplotypes localized on chromosomes 1 and 19 in the genes CR1 and APOE, APOC1, respectively. Our results confirm the role of the APOE and CR1 genes in the pathogenesis of Alzheimer’s disease in the Russian population.

Genetic diversity of a large number of populations is analyzed using various Y-chromosome markers. Genotyping of a wide range of novel highly informative SNP and YSTR markers shows that most of the Y-chromosome haplogroups can be divided not only into ethnically specific lineages but also into narrower sublineages and clusters of haplotypes. A significant extent of population and interethnic genetic differentiation is revealed. Most ethnic gene pools are characterized by the predominance or even complete dominance of specific SNPs across all major haplogroups, that is highly promising for the application in ethnic identification of biological samples of males.

The genetic structure of Khakass and Shor populations and clans (seoks) in terms of Y chromosome markers was investigated. The results of the analysis of haplogroup frequencies and YSTR haplotypes indicate that the Khakass and Shor seoks are related associations, in most cases having the same ancestor in the patrilineage. The gene pool of Khakass and Shors, more precisely a part marked by Y chromosome haplogroups, was shown to be primarily structured according to the generic principle. A strong genetic affinity of the members of the same seok was shown for the vast majority of the samples. Various Y chromosome haplogroups in the Khakass and Shor gene pools demonstrate their genetic affinity with Tuvans, Kets, Altaians, and Teleuts. This suggests the unity of the generalized gene pool of the indigenous South Siberian population and the genetic continuity of the populations living in this territory. Significant differences between the subethnic groups that are part of modern Khakass and Shors were revealed, where both of these ethnic groups were formed on the basis of common genetic components and demonstrate genetic affinity in various clans.

We describe the role of genomic and postgenomic technologies in the study of the preeclampsia genetic architecture in this review. Preeclampsia is a severe hypertensive disease of pregnancy that causes a significant level of maternal and perinatal morbidity and mortality. We emphasize the importance of integrative analysis of genomic, methylomic, transcriptomic, and proteomic data for characterizing the molecular mechanisms of preeclampsia, identifying new candidate genes and molecules for targeted therapy of this gestational complication.

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.

The human serine protease serine 2 TMPRSS2 is involved in the priming of proteins of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and represents a possible target for COVID-19 therapy. The TMPRSS2 gene may be co-expressed with SARS-CoV-2 cell receptor genes angiotensin-converting enzyme 2 (ACE2) and Basigin (BSG), but only TMPRSS2 demonstrates tissue-specific expression in alveolar cells according to single-cell RNA sequencing data. Our analysis of the structural variability of the TMPRSS2 gene based on genome-wide data from 76 human populations demonstrates that a functionally significant missense mutation in exon 6/7 in the TMPRSS2 gene is found in many human populations at relatively high frequencies, with region-specific distribution patterns. The frequency of the missense mutation encoded by rs12329760, which has previously been found to be associated with prostate cancer, ranged between 10% and 63% and was significantly higher in populations of Asian origin compared with European populations. In addition to single-nucleotide polymorphisms, two copy number variants were detected in the TMPRSS2 gene. A number of microRNAs have been predicted to regulate TMPRSS2 and BSG expression levels, but none of them is enriched in lung or respiratory tract cells. Several well-studied drugs can downregulate the expression of TMPRSS2 in human cells, including acetaminophen (paracetamol) and curcumin. Thus, the interactions of TMPRSS2 with SARS-CoV-2, together with its structural variability, gene&ndash, gene interactions, expression regulation profiles, and pharmacogenomic properties, characterize this gene as a potential target for COVID-19 therapy.

PURPOSE: Comparative analysis of multilocus imprinting disturbances (MLIDs) in miscarriages from women with sporadic (SPL) and recurrent pregnancy loss (RPL) and identification of variants in the imprinting control gene NLRP7 that may lead to MLIDs. METHODS: Chorionic cytotrophoblast and extraembryonic mesoderm samples from first-trimester miscarriages were evaluated in 120 women with RPL and 134 women with SPL; 100 induced abortions were analyzed as a control group. All miscarriages had a normal karyotype. Epimutations in 7 imprinted genes were detected using methyl-specific PCR and confirmed with DNA pyrosequencing. Sequencing of all 13 exons and adjusted intron regions of the NLRP7 gene was performed. RESULTS: Epimutations in imprinted genes were more frequently detected (p

The underrepresentation of non-Europeans in human genetic studies so far has limited the diversity of individuals in genomic datasets and led to reduced medical relevance for a large proportion of the world’s population. Population-specific reference genome datasets as well as genome-wide association studies in diverse populations are needed to address this issue. Here we describe the pilot phase of the GenomeAsia 100K Project. This includes a whole-genome sequencing reference dataset from 1,739 individuals of 219 population groups and 64 countries across Asia. We catalogue genetic variation, population structure, disease associations and founder effects. We also explore the use of this dataset in imputation, to facilitate genetic studies in populations across Asia and worldwide., Using whole-genome sequencing data from 1,739 individuals, the GenomeAsia 100K Project catalogues genetic variation, population structure and disease associations to facilitate genetic studies in Asian populations and increase representation in genetics studies worldwide.

Populations of the indigenous ethnic groups of Northern Eurasia are of considerable interest for population genomics, both because they have been relatively poorly studied with the use of modern genomic technologies and owing to the specificity of their gene pools that developed in various genetic-demographic conditions. We used genotype data on 242 179 autosomal SNPs of 876 individuals to search for regions with runs of homozygosity of more than 1 Mb. For Siberian populations, the number of runs of homozygosity and their total length was higher than for other populations of Northern Eurasia.

Obesity is one of the global health problems resulting in significant economic and social damage in both developed and developing countries. Overweight and obesity are key risk factors of diabetes and cardiovascular and oncological diseases that cause high morbidity and mortality. In the present paper, the method of multiplex genotyping of polymorphic variants of genes associated with obesity and variability of body mass index (BMI) was developed on the basis of multilocus PCR and MALDI-TOF mass spectrometry of DNA molecules. The frequencies of 51 single-nucleotide polymorphisms of obesity candidate genes in a population sample of Russians in Kemerovo were characterized. The results obtained were compared with the data for populations from the 1000 Genomes project. The association of markers rs12446632 of the LOC105371116 locus and rs16851483 of the RASA2 gene with BMI variability in the Russian population of Kemerovo was shown.

Human adaptation to extreme climatic and geographic conditions mediated by natural selection may be one of the major factors for formation of genetic structure in North Eurasian populations. Using data on a genome-wide set of single nucleotide polymorphisms (SNPs), we searched for the signals of positive selection in five populations of Siberia and the Russian European North. From 113 to 185 genomic regions with extended homozygous haplotypes blocks containing altogether 771 genes were found in each of the populations. Cross-population search of the selection targets resulted in about 150 genomic regions, 57 of which overlap with the results of haplotype analysis in individual populations. Genomic loci with the most profound signals of positive selection in northern populations include regions of SLC30A9, CACNA1C, KCNQ5, ABCA1, ALDH1A2, CSMD1, RBFOX1, and WWOX, as well as some other genes. Bioinformatics analysis demonstrated that major biological processes where selection targets are implicated are those conferring the response to external stimuli, including proteins, nutrients, and glucose, and defense reactions, including inflammatory immune response. The network of protein-protein interactions of genes under positive selection forms distinct clusters related to a number of biological processes indicated above. Results of the study indicate that non-neutral microevolution mechanisms may play a substantial role in genetic structuring of the human populations during long-term adaptation to unfavorable environmental conditions.

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.

We provide an overview of the recent achievements in psychiatric genetics research in the Russian Federation and present genotype-phenotype, population, epigenetic, cytogenetic, functional, ENIGMA, and pharmacogenetic studies, with an emphasis on genome-wide association studies. The genetic backgrounds of mental illnesses in the polyethnic and multicultural population of the Russian Federation are still understudied. Furthermore, genetic, genomic, and pharmacogenetic data from the Russian Federation are not adequately represented in the international scientific literature, are currently not available for meta-analyses and have never been compared with data from other populations. Most of these problems cannot be solved by individual centers working in isolation but warrant a truly collaborative effort that brings together all the major psychiatric genetic research centers in the Russian Federation in a national consortium. For this reason, we have established the Russian National Consortium for Psychiatric Genetics (RNCPG) with the aim to strengthen the power and rigor of psychiatric genetics research in the Russian Federation and enhance the international compatibility of this research.The consortium is set up as an open organization that will facilitate collaborations on complex biomedical research projects in human mental health in the Russian Federation and abroad. These projects will include genotyping, sequencing, transcriptome and epigenome analysis, metabolomics, and a wide array of other state-of-the-art analyses. Here, we discuss the challenges we face and the approaches we will take to unlock the huge potential that the Russian Federation holds for the worldwide psychiatric genetics community.

COVID-19 patients with acute respiratory distress syndrome (ARDS) have an immune imbalance when systemic inflammation and dysfunction of circulating T and B cells lead to a more severe disease. Using TREC/KREC analysis, we studied the level of mature naive T and B cells in peripheral blood of COVID-19 patients and its relationship with clinical and laboratory data. TREC/KREC analysis was performed by multiplex real-time quantitative PCR on a sample of 36 patients aged 45 years or younger. The reduced TREC/KREC level was observed in ARDS patients compared with non-ARDS patients, and similar results were found for the deceased patients. During days 6 to 20 of hospitalization, a higher neutrophil-to-lymphocyte ratio (NLR) was detected in ARDS patients compared with non-ARDS patients. TREC/KREC negatively correlated with NLR; the highest correlation was recorded for TREC per 100,000 cells with the coefficient of determination R2 = 0.527. Thus, TREC/KREC analysis is a potential prognostic marker for assessing the severity and outcome in COVID-19.

Background and Aims Percutaneous renal biopsy is essential tool in nephrology but it is invasive procedure that can lead to complications, including gross hematuria, clinical significant haematoma and infection. The aim of the study was to determine the nature and incidence of PRB complications and the impact of biopsy results on treatment strategy. Method 82 patients (male – 42, female – 40) with a median age of 43.5 (Q1; Q3 – 34;71) years, BMI 26.4 (22.9; 30.6) were included in retrospective study of all native kidney biopsies performed at our institute from January 1, 2016 to December 31, 2019. An informed consent was mandatory in all patients. The indications for biopsies were nephrotic syndrome, 24-hour proteinuria ≥ 1g, nephritic syndrome, renal failure of unknown origin. The median duration of kidney disease was 9.5 (3.0; 26.6) months, serum creatinine level - 135 (87; 197) μmol/l, eGFR (CKD-EPI formula) – 52.9 (26.6; 83.7) ml/min/1.73 m2, 24-hour proteinuria – 2.8 (1.2; 5.4) g. All biopsies were percutaneous, ultrasound-guided and were performed under local anesthesia in prone position with a 16G needle. Medications that may increase bleeding risk (anticoagulants, antiplatelet agents, and nonsteroidal anti–inflammatory drugs) was stopped before PRB. Immediately after the biopsy, bed rest and vital signs monitoring was prescribed for 12 hours. In the absence of complications, a control kidneys ultrasound was performed 24 hours after biopsy; if complications were suspected, regarding to the local protocol. We prescribed prophylactic antibiotics to the patients with a hematoma volume > 100 ml. All biopsy specimens were sent to tertiary laboratory of renal pathology and evaluated by light and immunofluorescence (IF) microscopy; electron microscopy was not used in our study. Biopsy samples were considered satisfactory for diagnosis if they contained five or more glomeruli. Results Post-biopsy complications included gross hematuria – 19 of 82 (23.5%) patients, haematomas ≤ 100 ml – 17 (20.7%), haematomas > 100 ml – 8 (20.7%), pain in the puncture site requiring the administration of analgesics – 2 (2.4%). No death, infections, bladder obstruction or nephrectomy due to biopsy complications was registered. One (1.2%) patient required blood transfusion. We identified renal arteriovenous fistula which did not require special treatment in one (1.2%) patient 2 months after PRB. We found no differences in the incidence of post-biopsy haematomas by gender, age, or BMI. Haematomas were significantly more common in patients with higher mean blood pressure and serum creatinine levels (Fig.1, A, B). In one case (1.2%) the biopsy was inadequate. The results of PRB were varied, including unexpected findings. IgA nephropathy was found in 23 of 81 (28.4%) patients, focal segmental glomerulosclerosis – in 21 (25.9%), membranous nephropathy – in 9 (11.1%), pauci-immune crescentic glomerulonephritis – in 6 (7,4%), lupus nephritis – in 2 (2.4%), membranoproliferative glomerulonephritis – in 2 (2.4%) - one with polyclonal Ig+/C3+ on IF and one - with monoclonal IgG kappa+, C3 nephropathy – in 1 (1.2%), AL-amyloidosis – in 2 (2.4%), light chain deposit disease – in 1 (1.2%), hypertensive nephropathy – in 1 (1.2%), diabetic nephropathy – in 3 (3.7%), tubulointerstitial nephritis – 5 (6.2%), thrombotic microangiopathy – in 2 (2.4%), diffuse nephrosclerosis – in 2 (2.4%), renal tuberculosis – in 1 (1.2%). According to the results of the biopsy, pathogenetic treatment was first prescribed to 43 of 81 (53.1%) patients, changed – in 17 (21%), treatment remained unchanged – in 8 (9.9%) cases. Thirteen (16%) patients were referred for additional examination by a hematologist and rheumatologist. Conclusion Biopsy of native kidney is a high diagnostic value and safe procedure with a low risk of major complications. Treatment was changed significantly after biopsy in 74% of patients in our study.

Background and Aims Post-transplant hypercalcemia is common after successful kidney transplantation in patients with chronic kidney disease (CKD) and can be partially explained by the side effects of concomitant therapy. We aimed to evaluate the prevalence of hypercalcemia among recipients of kidney transplant and its relationship with vitamin D supplementation. Method We performed a cross-sectional study of 236 patients underwent successful kidney transplantation in our clinic. Median age was 49 [Q1-Q3: 39; 58] years, mean estimated glomerular filtration rate (eGFR) was 51,1±21,8 ml/min/1,73 m2. Most of the patients received hemo- or peritoneal dialysis treatment, pre-emptive transplantation was performed in 6% cases. For those previously received dialysis, median duration of any type of dialysis was 21 [Q1-Q3: 11; 36] months. Median time after transplantation reached 42 [Q1-Q3: 19; 75] months. Target range for total serum Ca was defined according to National guidelines on CKD-MBD as 2,1 - 2,5 mmol/l. Results In our cohort median serum total Ca level was 2,41 [Q1-Q3: 2,36; 2,56] mmol/l. Hypercalcemia was encountered in 21% (7 of 33) cases during the first year after transplantation and in 30% (61 of 203) – after first year. Serum total Ca weakly correlated with iPTH (ρ= 0,282 [95%CI: 0,15; 0,4], р Conclusion We observed a high prevalence of hypercalcemia in kidney transplant patients, that was not associated with transplant function or time after transplantation. Our data suggest usage of active vitamin D to be safer than cholecalciferol to prevent hypercalcemia development in renal allograft recipients.

Background and Aims Mineral and bone disorders (MBD) are common after successful kidney transplantation in patients with chronic kidney disease (CKD). We aimed to evaluate the prevalence of biochemical abnormalities among recipients of kidney transplant. Method We performed a cross-sectional study of 236 patients underwent successful kidney transplantation in our clinic between 2007 and 2019. Median age was 49 [Q1-Q3: 39; 58] years, mean estimated glomerular filtration rate (eGFR) was 51,1±21,8 ml/min/1,73 m2. Most of the patients received hemo- or peritoneal dialysis treatment, pre-emptive transplantation was performed in 6% cases. For those previously received dialysis, median duration of any type of dialysis was 21 [Q1-Q3: 11; 36] months. Median time after transplantation reached 42 [Q1-Q3: 19; 75] months. We evaluated serum intact parathyroid hormone (iPTH), total calcium (Ca), phosphorus (P) and alkaline phosphatase (AP) levels. Target ranges were defined according to National guidelines on CKD-MBD as follows: 2,1 - 2,5 mmol/l for total Ca, 0,87 – 1,49 mmol/l for P; normal AP level is defined considering a gender (53-128 Е/l for men, 42-98 Е/l for women). Target iPTH level for optimal and slightly decreased transplant function (corresponding chronic kidney diasease (CKD) stage 3T) was defined as 35-70 pg/ml, for eGFR corresponding CKD 4T – as 70-110 pg/ml, for CKD 5T – as 70-150 pg/ml. Results In our cohort normal iPTH level was observed only in 13% cases, whereas 84% of the patients had hyperparathyroidism. iPTH inversely correlated with eGFR (ρ= -0,454 [95%CI: -0,55; -0,34], р Conclusion We observed a high prevalence of biochemical abnormalities in kidney transplant patients confirming that transplantation itself does not cure mineral and bone disorders in CKD patients.

Background and Aims To analyze the screening and prognostic value of various diagnostic signs of central vein stenosis (CVS). Method The retrospective study included 549 patients with AVF/AVG dysfunction. 211 patients were diagnosed with CVS, other patients had lesions of peripheral venous segments. In case of vascular access dysfunction, patients were examined according to the local protocol: ultrasound examination of peripheral (to exclude damage of the peripheral AVF segments) and central veins (at an accessible length) was performed, followed by CT angiography or percutaneous angiography, if necessary. Results Among various clinical signs only limb edema and dilated veins on the chest demonstrated high sensitivity. Aneurysmal dilatation of an AVF was more common in peripheral lesions (CVS RR Ultrasound signs have low screening accuracy, but high prognostic values. In other words, in the presence of ultrasound signs, patient is likely to have CVS with high probability – table 3. When comparing the frequency of correct and incorrect classifications for different types of lesion, ultrasound accuracy exceeds the clinical picture for types of lesion 1C and 1D (according to the types of lesion in Society of Interventional Radiology Reporting Standards for Thoracic Central Vein Obstruction, doi: 10.1016/j.jvir.2017.12.013): RR= 3,433 [95% CI 2,074; 6,132], p0.9999, respectively. In total, incorrect CVS type classifications is noted in 30.7% of cases when using ultrasound imaging. CT angiography and percutaneous angiography are almost 100% effective in the diagnosis of CVS. However, CT angiography is not always informative when AVF is functioning and the volume blood flow is high. In turn, percutaneous angiography does not always allow to assess the condition of the veins of the contralateral side. At the same time, correct detection of lesion type is pivotal to determine the future strategy of providing the patient with permanent vascular access. For example, the patient has very little chance to get functional AVF in case of with two-sided subclavian vein stenosis. Conclusion The CVS diagnostics should be comprehensive, using different methods for screening, confirming CVS and determining of it type.

Background and Aims The prevalence of central vein stenosis (CVS) in patients on hemodialysis (HD) is difficult to be assessed directly. This is mainly caused by the variety of clinical signs and the high frequency of asymptomatic CVS. Aim: to assess the frequency of occurrence of various CVS forms in HD patients. Method The retrospective observational study is based on the results of treatment of 1865 HD patients who underwent diagnostic and therapeutic procedures on vascular access in our center. In case of vascular access dysfunction, patients were examined according to a local protocol: ultrasound of the peripheral (to exclude lesion of peripheral AVF segments) and central veins (over the available length), followed with CT-angiography or percutaneous angiography, if necessary. Results AVF/AVG dysfunction was observed in 29.4% of patients (549 of 1865). 211 patients were diagnosed with CVS. The prevalence of CVS was 11.3% (211 of 1865) among all HD patients and 38.4% (211 of 549) in patients with AVF dysfunction. Among patients with CVS, 37% (78 of 211) had vein lesions without clinical symptoms or with minimal manifestations (a tendency to decrease KT/V). The prevalence of asymptomatic CVS was 4.2% (78 of 1865) in the general population of HD patients and 14.2% (78 of 549) in patients with AVF dysfunction. In case of asymptomatic CVS it was detected by an ultrasound examination during CVC implantation (N=38), during unsuccessful attempts to implant CVC (N=29), in the case of recurrent AVF thrombosis without underlying peripheral segments lesion (N=9) or during echocardiography (N=2). The prevalence of asymptomatic CVS among patients without AVF dysfunction was 5.9% (78 of 1316). True prevalence of subclinical CVS among HD patients without obvious signs of AVF dysfunction may vary widely. A total of 48.8% (103 of 211) of all CVS cases were treated. At the same time, in 10.7% (11 of 103) of cases, patients did not present symptoms of CVS, and surgery was performed due to recurrent AVF thrombosis without damage of the peripheral parts of AVF. Patients with clinically manifest CVS who received endovascular interventions had a significantly higher risk of AVF loss compared to patients with asymptomatic CVS: HR=2.566 [95% CI 1.706; 3.86], log rank p The use of CVC is a known risk factor of CVS development. We analyzed the relationship of CVS risk with multiply CVC placements and catheter dwell time using the Cox proportional hazards regression model (fig. 2). In the univariate model, a greater No of CVCs as well as longer time in place increased the risk of CVS. In the multivariate model (χ2=105.516, df=2, p Conclusion The prevalence of both symptomatic and asymptomatic forms of CVS in HD patients is high. Patients with vascular access dysfunction should be carefully examined to identify the asymptomatic CVS. The mean No of catheterizations is a more important risk factor of CVS than longer catheter dwell time.

Background and Aims According to the current KDIGO guidelines, angioplasty should be preferred procedure for treatment of CVS instead of the bare metal stents or self-expanding stent-grafts placement. However, bare stents are still significantly more affordable than stent grafts. Aim: comparative analysis of the results of isolated balloon angioplasty (BA) and combined technique (BA with a stent placement in HD patients with central vein stenosis (CVS). Method A retrospective study included 62 patients with functional AVF and confirmed CVS: subclavian, brachiocephalic veins, vena cava inferior, or multiple lesions. In 39 patients, stents were not used; isolated balloon angioplasty (BA) was performed. In 23 patients we used bare metal stents during the first endovascular treatment. Results The use of stents leads to increase of primary patency (the time interval between the first and second endovascular interventions) – fig. 1A; HR (BA only vs. stenting) 2.064 [95% CI 1.252; 3.404], p = 0.0017. The use of stents allows to increase secondary patency (the time interval between the first endovascular intervention and the complete cessation of the use of AVF): HR=2.03 [95% CI 1.232; 3.347], p = 0.0021; fig 1B. Total need for surgical interventions did not differ: BA only 1.511 [95% CI 1.225; 1.843] and BA+stenting 1.277 [95% CI 0.997; 1.611] per 10 patient-months, incidence rate ratio 1.183 [95% CI 0.872; 1.612] p=0.2822. The second isolated BA allowed to increase patency compared to the first (HR of AVF function loss or relapse 0.512 [95% CI 0.32; 0.818], log rank p=0.001), and the third compared to the second isolated BA (HR=0.607 [95% CI 0.384; 0.959], log rank p=0.0157). The fourth isolated BA also showed a slight increase in AVF patency, but in this case we observed no significant difference with the previous intervention (HR= 0.783 [95% CI 0.501; 1.225], log rank p=0.2433). In the case of BA+stenting, the second intervention, which was consisted of stent recanalization, allowed to increase patency of the AVF (HR= 0.433 [95% CI 0.231; 0.813], log rank p= 0.0014), but the third intervention was no longer accompanied by a significant increase in patency (HR= 0.873 [95% CI 0.489; 1.558], log rank p= 0.629) and AVF function was completely lost. Conclusion The use of stents leads to a moderate increase in the median patency of AVF and a significant increase in the proportion of patients with functional AVF in the long-term period. However, repeated surgeries are significantly less effective than in a case of isolated BA. Therefore, we consider isolated BA to be the optimal treatment strategy, and stenting should be used only if the isolated BA does not result in clinical improvement. Multiple endovascular interventions can extend the duration of AVF functioning, however, in our study, AVF function was completely lost up to 52 months after the clinical manifestation of CVS in all patients. Thus, isolated BA and BA combined with a bare metal stent placement cannot be considered as a definitive treatment of CVS. Endovascular interventions provide only the necessary amount of time to create vascular access on the contralateral side or for shift of modality of renal replacement therapy.

Background and Aims It is well-known that central vein stenosis (CVS) significantly reduces the time of AVF functioning. At the same time, according to current guidelines (KDIGO, European Vascular Surgery Society, European Best Clinical Practice), only clinically significant CVS should be treated. Often, CVS becomes clinically manifest due to a significant increase of AVF volume blood flow (Qa) through the matured dialysis access. Aim: to assess the effect of Qa reduction on the CVS clinical course. Method We performed a retrospective study included 56 patients who underwent Qa reduction as the first step of treatment, and 62 patients who received endovascular interventions without Qa reduction (balloon angioplasty supplemented with stenting if necessary). Blood flow reduction was performed using banding under intraoperative ultrasound control. Results Surgical banding leads to a clinically obvious and statistically significant decrease in Qa in all patients – fig. 1. In contrast, after endovascular intervention most of the patients show a modest but statistically significant increase in Qa - fig. 2. All surgeries were performed to reduce the severity of clinical manifestations of CVS. AVF was better available for immediate cannulation after endovascular interventions than after banding: RR=4,537 [95%CI 1,416; 14,84], p=0,0116. However, the probability of successful cannulation at the third postoperative HD session did not differ between groups: RR=3.024 [95%CI 0.674; 13.67], p=0.2126. Taking in consideration these findings, we can conclude that the short-term results of Qa reduction are satisfactory. After Qa reduction in case of recurrence of CVS symptoms or absence of their complete resolving, we supplemented the treatment with endovascular interventions. Both primary and secondary patency were significantly better than in the case of endovascular interventions without Qa reduction – fig. 3. Moreover, in patients who underwent endovascular interventions without Qa reduction, higher Qa values were associated with decrease of the primary and secondary patency – fig. 4. So, increasing or maintaining large Qa values after endovascular intervention may be an important risk factor for CVS relapse and AVF function loss. Conclusion Qa is an important factor of CVS clinical manifestation. When determining treatment strategy, it is necessary to evaluate Qa first and reduce it, if necessary. Manage of Qa allows to transfer manifest CVS into its subclinical course, which itself leads to improved treatment results. Endovascular interventions are the preferred treatment of CVS with clinical manifestations in a case of underlying normal or suboptimal Qa.

Background and Aims For many years we observed aging of HD population: the proportion older adults is increasing. These patients have extremely low kidney transplantation rate, so vascular access is not a temporary option, but an important factor until the end of life. At the same time in older adults life expectancy is lower and the risks of cardiovascular events are much higher than in the general population of HD patients. We analyzed the results of providing elderly patients with vascular access. Method The study included 618 patients (age ≥ 65) from the Moscow region CKD patients register. Results With the current practice, only about 60% of elderly patients begin HD within a year after the AVF creation (taking into account competing events) - fig. 1. The proportion of patients with brachiocephalic AVF was significantly higher than in younger patients: 41,3% vs. 16,4%. It is known that proximal AVF have a much greater tendency to increase the volume blood flow (and therefore – cardiopulmonary recirculation) than distal. Thus, elderly patients begin HD with a more adverse comorbid background. Therefore, elderly patients have an additional risk factor - the onset of HD after 65 years – fig 2. Paradoxically, but according to our data, patients who started HD after 65 years had a worse prognosis than patients who reached 65 while already on HD. At the same time, the onset of HD with CVC with the subsequent successful conversion to AVF was not associated with a significant increase in the risk of death («CVC-AVF» factor). Only if CVC remained the only vascular access («CVC» factor), the risk of death is increase significantly. This is indirect evidence in favor of the fact that in elderly patients, the AVF must be created closer to the expected start of HD. In adjusted model, the significant risk factors also were diabetes, systemic diseases (factor «Other») and comorbidity (CIRS score), but not age. Among patients who started HD with CVC, all patients received functional AVF or died within 11 months – fig. 3. Infections occur with the same frequency (CVC-AVF vs. AVF) and clinical manifestations of central venous insufficiency do not have time to occur during the expected life period in most patients: incidence rate ratio IRR 1.21 [0.91; 1.31] and IRR 1.11 [0.93; 1.19], respectively. Is a conversion of AVF to CVC can improve the outcomes in older adults? In some patients probably - yes. Since many elderly patients initially have heart failure and a reduced cardiac output (CO), the potential for compensating of AVF blood flow (Qa) is significantly less than in younger patients. We found that this leads to the fact that in the elderly, at a lower Qa value, a greater value of cardiopulmonary recirculation is noted. Even with a Qa value of 1.0-1.2 l/min, the Qa/CO value can reach ≈ 25%, which is associated with a significant risk of death. But there is good news: in the older adults some criteria are more informative than in the general population of HD patients: AUC-ROC of ejection fraction (EF), estimated pulmonary artery systolic pressure (ePASP) and Qa/CO – 0.821, 0.804 and 0.846, respectively vs. 0.654, 0.726 and 0.764. The bad news: the decision to convert from a functional AVF to a CVC is a very difficult choice. Specific indications are still not determined. We believe that it is necessary to consider the conversion from AVF to CVC in a case of decompensated heart failure, with EF50-55 or Qa/CO>20-25%, if the reduction of Qa does not improve these parameters. In this case, conversion from CVC to AVF may improve the prognosis. Older patients require more careful monitoring than younger patients. Conclusion 1. The start of HD with CVC is not a problem in case of subsequent successful conversion to AVF. 2. The most important risk factors is comorbidity, starting of HD after 65 years, diabetes and only then - vascular access type. 3. Given all the facts, in the older adults we tend to create an AVF closer to start of HD than in the general HD population.

Background In Russia, each transplant center has its own separated waiting list. This significantly reduces the ability to select the optimal recipient in terms of tissue compatibility. Aim to perform a multivariate analysis of the effect of the number of epitope mismatches on transplant survival. Method An observational retrospective cohort study was performed, which included 824 adult recipients. All patients underwent transplantation of a cadaveric kidney compatible by blood group. The endpoint was considered transplant loss. The death-censored graft survival was evaluated. The calculation of the number of epitope mismatches (EpMM) was carried out using information from publicly available resources about the population frequency of haplotypes and the repertoire of epitopes with confirmed immunogenicity. All possible combinations of the donor and recipient genotypes were compiled, and the probability of each combination was calculated. Then, for each combination with nonzero probability the number of donor epitopes absent in the recipient was determined. After that, the weighted average EpMM was calculated, where the weighted coefficient was the normalized probability of occurrence of each combination. Results All recipient donor pairs had HLA incompatibilities (HLA MM): 1.9% - 1 HLA MM, 6.7% - 2 HLA MM, 29.9% - 3 HLA MM, 38.5% - 4 HLA MM, 18, 1% - 5 HLA MM, 4.9% - 6 HLA MM. EpMM increased with increase of the HLA MM count, but not linearly: 6 [interquartile range – IQR 4; 7] (from 2 to 7), 12 [IQR 7.74; 17.25] (from 4 to 20), 18 [IQR 14; 22] (from 8 to 28), 24 [IQR 20; 30] (from 10 to 33), 30.5 [IQR 25; 37] (from 13 to 35) and 36 [IQR 26.5; 44.5] (from 15 to 40) for 1, 2, 3, 4, 5, and 6 HLA MM, respectively. Significant risk factors for graft loss in the adjusted multivariate model were: HLA MM (1 – HR 1; 2– HR 1.24 [95% confidence interval - 95% CI 0.7; 2.15], p = 0.344; 3– HR 1, 48 [95% CI 0.86; 2.33], p = 0.251; 4– HR 1.88 [95% CI 1.32; 2.52], p When included EpMM in the model, significant risk factors were: EpMM ( Validation of this method of assessing immunological load on a larger sample of patients is required. The list of immunogenic epitopes is constantly updated. The accumulation of this knowledge can improve results of transplantation. Conclusion The number of epitope mismatches remains an important factor in long-term transplant survival even when adjusted for other risk factors: the number of HLA mismatches, the donor type and the level of presensitization. This determines the possibility of using this method as an adjuvant in the donor-recipient pair selection. At the same time, there is a theoretical possibility of using this method as an alternative to the traditional assessment of tissue compatibility of a donor and a recipient.

Background and Aims In Russia, when choosing a donor-recipient pair, the “waiting time” factor has very little weight. Aim: to analyze the survival of patients on the waiting list for kidney transplantation and the results of transplantation depending on the duration of waiting. Method We performed a retrospective observational analysis that included 1,197 patients on the waiting list. The end point was exclusion from the waiting list (WL). The causes for exclusion (death, exclusion due to deterioration of the comorbid background or transplantation) were considered in terms of competing risks. Results In total, 72.5% of patients reached the end point: 21.1% of them died, 11% were excluded, and 40.4% underwent transplantation. Kaplan-Meier estimate showed that cumulative risk of death was 80.4% [95% CI 77.9; 88.6], of exclusion – 77.9% [95% CI 65.4; 88.2], of transplantation – 63.6% [95% CI 58.3; 69] after 10 years on the waiting list. However, such an assessment cannot be directly interpreted as a prediction of the relevant event risk for the patient in the WL, because it does not take into account competing events. According to a balanced assessment of the competing risks (Fine and Gray regression model), cumulative incidence was 30.9% [95% CI 27.7; 34.2] for death, 18.2% [95% CI 15.5; 21.1] for exclusion and 49.4% [95% CI 46; 52.6] for transplantation after 10 years on WL. The probability of transplantation was significantly higher than the risk of death up to and including 5 years of waiting (incidents rate ratio – IRR 1.769 [95% CI 1.098; 2.897]). When waiting 7 to 8 years, the probability of transplantation was less than the risk of death: IRR 0.25 (95% CI 0.093; 0.588; p=0.0009) – fig 1. Of the 483 recipients, 61 died and 119 returned to dialysis. The risk of graft loss after 10 years was 68.5% [95% CI 57.5; 79.1] and the risk of death of a recipient with a functioning graft was 48.3% [95% CI 34.7; 63] according to Kaplan-Meier estimate. The cumulative incidence was 30.8% [95% CI 23.3; 38.5] and 55.7% [95% CI 46.6; 63.5] according to Fine and Gray estimate, respectively. The risk of death after transplantation increases significantly when waiting for more than 6 years – IRR 4.325 [95% CI 1.649; 10.47], p=0.0045 relative to a shorter waiting period – fig 2. With an increase in the waiting period, the comorbid background (CIRS scale) deteriorates significantly, even adjusted for the initial patient condition: the partial correlation r=0.735; p Conclusion : 1. In the context of competing risks, the Fine and Gray estimate gives a more balanced risk assessment compared to the Kaplan-Meier method. 2. Increasing the waiting time for transplantation significantly increases the risk of death of the candidate on the waiting list and reduces the probability of transplantation, as well as increases the risk of death of the recipient after transplantation. Apparently, this is mainly due to the deterioration of the comorbid background.

Background and Aims cardiopulmonary recirculation (CRP) is one of the most informative instrumental parameters, which are widely used to predict adverse cardiovascular events. The CRP is calculated on the basis of two indirectly measured estimates. We observe a significant variability in CRP, the reason for which we have tried to explain. Method The prospective study included 88 patients with native AVF. At the first stage, we evaluated the inter- and inner-observer agreement of AVF volume blood flow (Qa) measurement with color duplex ultrasound. Two specialists with 5-7 years of experience measured Qa twice on the brachial artery, twice on fistula vein, after that - twice measured cardiac output before HD and one time after HD. Ultrafiltration during HD was 1.9±0,5 l. Results We observed good concordance between measurements on the brachial arteria by one specialist (fig 1A) and by two specialists (fig. 1B). There was poor concordance between the brachial artery and the fistula vein, even if the measurement was performed by one specialist (fig. 1C). Qa measurement on the fistula vein has a low repeatability, even if the measurement was performed by one specialist: the variance is very high (fig. 1 D). We observed a good concordance between measurements (fig. 2A) and between specialists (fig. 2B) in CO assessment. The main pitfalls of CPR-based cardiovascular risk stratification are related to the fact that CO changes significantly after HD (fig. 3A), while Qa values remain relatively stable (fig. 3B): the QA before and after HD difference is statistically significant, but it is minimal. Median CO decrease was 13.4% (maximum 26.6%), while median of Qa decrease was 1.7% (maximum 6.1%). This leads to a significant increase of the CPR value after HD, which can reach 40%(!) in some patients (absolute increase – 0.11). Conclusion Qa assessment should be performed on the brachial artery. After HD, there is a significant decrease in cardiac output (even with moderate ultrafiltration) with relatively stable AVF volume blood flow. This leads to a significant increase of CPR value after HD in some patients. Assessment of CPR before HD may lead to underestimation of cardiovascular risk.

Using massively parallel sequencing, the COL1A1 and COL1A2 genes were analyzed in 16 patients from 10 families with osteogenesis imperfecta types I, III, and IV. To analyze the mutations in these genes, a panel of primers was developed for sequencing the complete gene sequence. As a result of the work, 10 mutations were revealed: six of them are in the COL1A1 gene, four mutations in the COL1A2 gene. All mutations, except one, were previously described in the literature and were found in patients with various types of osteogenesis imperfecta. Missense mutations were identified in five families, nonsense mutations in two families, splice site mutations in two cases, and a frameshift mutation in one patient. Unique mutations that were not repeated in unrelated patients were found in all families. The revealed high heterogeneity of the spectrum of mutations in the COL1A1 and COL1A2 genes in osteogenesis imperfecta indicates the effectiveness of using MPS-based methods for the diagnosis of this pathology.

Methods and approaches to transforming traditional libraries focused on the collections, to the new type of libraries to be focused on comprehensive facilitation of user intellectual and creative activities and, correspondingly, on advancement of the society being served, are discussed. The author argues that the key principle for the regenerated libraries would be users’ intensive participation in their content development, with the projects as the key method, number of users participating in intellectual and creative activities as the main criteria; and the libraries’ transforming into the community development center as the principal result of this transformation.

This study investigated whether common polymorphisms of cytochrome P450 2J2 (CYP2J2), a major enzyme that controls the biosynthesis of vasoactive epoxyeicosatrienoic acids, are collectively involved in the molecular basis of essential hypertension (EH). A total of 2314 unrelated Russian subjects from the Kursk (discovery sample: 913 EH patients and 645 controls) and Belgorod (replication sample: 345 EH patients and 411 controls) regions were recruited for this study. Eight single nucleotide polymorphisms (SNPs), including rs890293, rs11572182, rs10493270, rs1155002, rs2280275, rs7515289, rs11572325, and rs10889162, of CYP2J2 were genotyped using the MassARRAY 4 system and TaqMan-based assays. Significant associations were identified among the SNPs rs890293 (OR = 2.17, 95%CI 1.30-3.65), rs2280275 (OR = 1.59, 95%CI 1.10-2.37) and rs11572325 (OR = 1.89, 95%CI 1.22-2.95) and the risk of EH in females from the Kursk population. Sixteen CYP2J2 genotype combinations only showed significant associations with EH risk only in females. A common haplotype, T-T-G-C-C-C-T-A, increased the risk of EH in females. The bioinformatic analysis enabled identification of the SNPs that possess regulatory potential and/or are located within the binding sites for multiple transcription factors that play roles in the pathways involved in hypertension pathogenesis. Moreover, the polymorphisms rs890293, rs2280275, and rs11572325 were found to be significantly associated with hypertension risk in the Belgorod population. In conclusion, the rs2280275 and rs11572325 SNPs of CYP2J2 may be considered novel genetic markers of hypertension, at least in Russian women. However, sex-specific associations between CYP2J2 gene polymorphisms and hypertension require further investigation to clarify the specific genetic and/or environmental factors that are responsible for the increased disease susceptibility of women compared to that of men.