[Clinical and laboratory characteristics of arginine vasopressin resistance, caused by a new homozygous mutation p.R113C in AQP2].

Congenital nephrogenic diabetes insipidus (CNDI, arginine vasopressin resistance) is a rare inherited disorder characterized by insensitivity of the kidney to the antidiuretic effect of vasopressin. NDI is clinically characterized by polyuria with hyposthenuria and nocturia and polydipsia. In the majority of cases, about 90%, nephrogenic diabetes insipidus is an X-linked recessive disorder caused by mutations in the AVP V2 receptor gene (AVPR2). In the remaining cases, about 10%, the disease is autosomal recessive or dominant and, for these patients, mutations in the aquaporin 2 gene (AQP2) have been reported. To date, the nucleotide variants registered in AQP2 were sporadic, there is no data on the presence of «frequent¼ mutations and the prevalence of the disease both among the global population and among individual ethnic groups. In this paper, we describe 12 cases of arginine vasopressin resistance caused by a new homozygous mutation p.R113C in AQP2 presented among the indigenous population of the Republic of Buryatia.

Phase transformation in the "Brodie graphite oxide-acetonitrile" system - influence of the oxidizing level of the material.

Reversible phase transformation in the Brodie graphite oxide-acetonitrile system, which is intercalation or release of part of the sorbed liquid from the interplanar space accompanied by an increase or a decrease in interplanar distances, is commonly observed in twice-oxidized materials. We observed this phenomenon for once-, twice- and thrice-oxidized materials using the EPR spin probe technique, DSC, and temperature programmed XRD. It was shown that all materials under study formed similar low temperature (LT) and high temperature (HT) swollen structures with acetonitrile. The phase transformation of these structures is observed for materials with different oxidation levels in the same temperature range (∼20 K). The twice- and thrice-oxidized Brodie graphite oxides form swollen structures with the same parameters, while the once-oxidized material sorbs less acetonitrile at lower temperatures, but shows the same interplanar distances as those in twice- and thrice-oxidized materials. The spin probe technique has proven its sensitivity to the appearance of small amounts of the new forming swollen structures, which makes this method useful in studies of phase transformations.

Sorption of Polar Sorbents into GO Powders and Membranes.

The comparative study of sorption of polar substances acetonitrile and water into powders and membranes (>10 µm thick) of modified Hummers (HGO) and Brodie (BGO) graphite oxides was performed using isopiestic method (IM) and differential scanning calorimetry (DSC). Additional sorption data were obtained for pyridine and 1-octanol. Sorption measurements were accompanied by conventional XRD and XPS control. Electron paramagnetic resonance (EPR) was additionally used to characterize ordering of the membranes. The impact on sorption of synthetic procedure (Brodie or Hummers), method of making membranes, chemical nature of the sorbent, and method of sorption was systematically examined. It was demonstrated that variations in synthetic procedures within both Hummers and Brodie methods did not lead to changes in the sorption properties of the corresponding powders. Sorption of acetonitrile and pyridine was reduced by approximately half when switching from powders to membranes at ambient temperature. DSC measurements at a lower temperature gave equal sorption of acetonitrile into HGO powder and membranes. Water has demonstrated unique sorption properties. Equal sorption of water was measured for HGO membranes and powders at T = 298 K and at T = 273 K. It was demonstrated that lowering the orientational alignment of the membranes led to the increase of sorption. In practice this could allow one to tune sorption/swelling and transport properties of the GO membranes directly by adjusting their internal ordering without the use of any composite materials.

Important problems in the diagnosis and treatment of primary sclerosing cholangitis (based on the Russian consensus on diagnosis and treatment autoimmune hepatitis. Moscow, 2018).

The article is published based on the results of the Russian Consensus on the diagnosis and treatment of primary sclerosing cholangitis (PSC), discussed at the 44th annual Scientific Session of the CNIIG "Personalized Medicine in the Era of Standards" (March 1, 2018). The aim of the review is to highlight the current issues of classification of diagnosis and treatment of patients with PSC, which causes the greatest interest of specialists. The urgency of the problem is determined by the multivariate nature of the clinical manifestations, by often asymptomatic flow, severe prognosis, complexity of diagnosis and insufficient study of PSC, the natural course of which in some cases can be considered as a function with many variables in terms of the nature and speed of progression with numerous possible clinical outcomes. In addition to progression to portal hypertension, cirrhosis and its complications, PSC can be accompanied by clinical manifestations of obstructive jaundice, bacterial cholangitis, cholangiocarcinoma and colorectal cancer. Magnetic resonance cholangiography is the main method of radial diagnostics of PSC, which allows to obtain an image of bile ducts in an un-invasive way. The use of liver biopsy is best justified when there is a suspicion of small-diameter PSC, autoimmune cross-syndrome PSC-AIG, IgG4-sclerosing cholangitis. Currently, a drug registered to treat primary sclerosing cholangitis which can significantly change the course and prognosis of the disease does not exist. There is no unified view on the effectiveness and usefulness of ursodeoxycholic acid and its dosage in PSC. Early diagnosis and determination of the phenotype of PSC is of clinical importance. It allows to determine the tactics of treatment, detection and prevention of complications.

[DNA aptamers selection for breast cancer]. / Selektsiia dnk-aptamerov dlia diagnostiki raka molochnoi zhelezy.

A method of selection of DNA aptamers to breast tumor tissue based on the use of postoperative material has been developed. Breast cancer tissues were used as the positive target; the negative targets included benign tumor tissue, adjacent healthy tissues, breast tissues from mastopathy patients, and also tissues of other types of malignant tumors. During selection a pool of DNA aptamers demonstrating selective binding to breast cancer cells and tissues and insignificant binding to breast benign tissues has been obtained. These DNA aptamers can be used for identification of protein markers, breast cancer diagnostics, and targeted delivery of anticancer drugs.

[Characteristic of the Genetic Variability of Four Polymorphic Variants (rs2069705, rs17880053, rs11126176, and rs804271) in Representative Samples of Indigenous and Alien Populations of Siberia].

The variability of potentially important functional polymorphic variants rs2069705 (5'UTR of the IFNG gene), rs17880053 (near 5'UTR of the IFNGR2), rs11126176 (LOC100287361 pseudogene), and rs804271 (near 5'UTR of the NEIL2 gene) was characterized in representatives of four ethnic groups living in the Siberian region. These ethnic groups included three indigenous Mongoloid ethnic groups (Yakuts, the residents of the Republic of Sakha (Yakutia), Tuvinians from the Republic of Tuva, and Buryats from the Republic Buryatia) and the alien Russian population. All of the examined variants were polymorphic. The frequency of the rs2069705 allele C in Russians was 0.5833, while it was in a range from 0.7842 to 0.8967 in representatives of the indigenous populations. The frequency of rs17880053 deletion was 0.8073 in Russians and from 0.4474 to 0.5521 in the indigenous ethnic groups. The frequency of the rs11126176 allele A was equal to 0.5398 in Russians but was recorded with lower frequencies in indigenous ethnic groups (from 0.2722 to 0.4551). The frequency of the rs804271 allele Gwas 0.5215 in Russians and from 0.2527 to 0.4022 indigenous ethnic groups. With respect to the genotype structure, the alien Russian population was considerably distanced from indigenous Mongoloid populations. Specifically, the genetic distance was 0.0742 between Russians and Yakuts, 0.1365 between Russians and Tuvinians, and 0.1433 between Russians and Buryats. Among the Mongoloid indigenous ethnic groups of Siberia, Tuvinians and Yakuts were the most distant from each other (0.0262). The genetic distance was equal to 0.0151 between Yakuts and Buryats and 0.0127 between Buryats and Tuvinians.

[HEMOCHROMATOSIS IN CLINICIAN PRACTICE].

The paper presents the current data on the etiology, pathogenesis, clinical features, diagnosis and treatment of patients with hemochromatosis. Particular attention is given to hereditary hemochromatosis and its genetic diversity. The clinical example demonstrates the difficulty of a disease diagnostics caused by genetic polymorphism.

[Genetic subdivision of the Buryat population].

The results of an estimation of the level of subdivision in the Buryat ethnos (obtained oh the basis of data published by a number of research teams) are given. Altogether, information about 34 loci, including 25 diallelic loci and 9 STR loci, was analyzed. The results of the analysis, both for the diallelic polymorphic variants in genes predisposed to multifactorial diseases and for neutral STR markers, indicate the subdivision of the genetic structure of the different territorial groups of Buryats. The peculiarities of the ethnogenesis and heterogeneity of the settlement of Buryat tribes on the territory of residence are considered as one possible (but not the sole) explanation of the genetic heterogeneity of different territorial groups of Buryats. It is indicated that it is important to take into account information about the territorial, ethnic, and tribal affiliation of individuals (included in the studied groups) when planning studies aiming to establish a genetic component of the determination of pathological states in humans.

[Gene pool of Buryats: clinal variability and territorial subdivision based on data of Y-chromosome markers].

The structure of the Buryat gene pool has been studied based on the composition and frequency of Y-chromosome haplogroups in eight geographically distant populations. Eleven haplotypes have been found in the Buryat gene pool, two of which are the most frequent (N1cl and C3d). The greatest difference in haplogroup frequencies was fixed between the western and eastern Buryat samples. The evaluation of genetic diversity based on haplotype frequencies revealed that it has low values in most of the samples. The evaluation of the genetic differentiation of the examined samples using an analysis of molecular variance (AMOVA) shows that the Buryat gene pool is highly differentiated by haplotype frequencies. Phylogenetic analysis within haplo-groups N1cl and C3d revealed a strong founder effect, i.e., reduced diversity and starlike phylogeny of the median network of haplotypes that form specific subclusters. The results of a phylogenetic analysis of the haplogroups identified common genetic components for Buryats and Mongols.

The Genetic Diversity and Structure of Linkage Disequilibrium of the MTHFR Gene in Populations of Northern Eurasia.

The structure of the haplotypes and linkage disequilibrium (LD) of the methylenetetrahydrofolate reductase gene (MTHFR) in 9 population groups from Northern Eurasia and populations of the international HapMap project was investigated in the present study. The data suggest that the architecture of LD in the human genome is largely determined by the evolutionary history of populations; however, the results of phylogenetic and haplotype analyses seems to suggest that in fact there may be a common "old" mechanism for the formation of certain patterns of LD. Variability in the structure of LD and the level of diversity of MTHFRhaplotypes cause a certain set of tagSNPs with an established prognostic significance for each population. In our opinion, the results obtained in the present study are of considerable interest for understanding multiple genetic phenomena: namely, the association of interpopulation differences in the patterns of LD with structures possessing a genetic susceptibility to complex diseases, and the functional significance of the pleiotropicMTHFR gene effect. Summarizing the results of this study, a conclusion can be made that the genetic variability analysis with emphasis on the structure of LD in human populations is a powerful tool that can make a significant contribution to such areas of biomedical science as human evolutionary biology, functional genomics, genetics of complex diseases, and pharmacogenomics.

Ultrafast x-ray scattering of xenon nanoparticles: imaging transient states of matter.

Femtosecond x-ray laser flashes with power densities of up to 10(14) W/cm(2) at 13.7 nm wavelength were scattered by single xenon clusters in the gas phase. Similar to light scattering from atmospheric microparticles, the x-ray diffraction patterns carry information about the optical constants of the objects. However, the high flux of the x-ray laser induces severe transient changes of the electronic configuration, resulting in a tenfold increase of absorption in the developing nanoplasma. The modification in opaqueness can be correlated to strong atomic charging of the particle leading to excitation of Xe(4+). It is shown that single-shot single-particle scattering on femtosecond time scales yields insight into ultrafast processes in highly excited systems where conventional spectroscopy techniques are inherently blind.

[Of the article intraliver pregnancy cholestasis].

The article includes the contemporary information about prevalence, clinical history, the methods of diagnostics and treatment of the intraliver pregnancy cholestasis, and about the tactics of the supervision of the pregnant women with intraliver cholestasis.

[Results of a multicenter trial "Epidemiology of Gastroesophageal Reflux Disease in Russia" (MEGRE)].

AIM: To assess prevalence of gastroesophageal reflux disease (GERD) in Russia in MEGRE trial in 6 cities of the Russian Federatiion (Kazan, Kemerovo, Krasnoyarsk, Ryazan, St-Petersburg, Saransk). MATERIAL AND METHODS: Mayo Clinic questionnaire (USA) adapted for Russia was used to question 7812 people over 18 years of age from of random population sample. The symptoms (heartburn and regurgitation) were classified as frequent if they arose once a week and more often for the last 12 months, rare symptoms arose less often than once a week. The responders with frequent heartburn and/or regurgitation were regarded as persons with epidemiological quantitative criteria of GERD. RESULTS: Heartburn occurred in 47.5% responders: frequent in 9%, rare in 38.5%. Regurgitation occurred in 42.9%: frequent in 7.6%, rare in 35.3%. GERD prevalence was 13.3% (city range 11.3-14.3%). Frequent GERD symptoms are associated with frequent gaseous eructation (24.3%), chronic cough (22.9%), chest pain (15.1%), dysphonia (11.4%.). To stop heartburn, 88% responders took antacids, 32%--blockers of histamine H2-receptors and only 23%--inhibitors of proton pump. Only 52.8% responders with frequent chest pain and 29.3% those with frequent heartburn visited a doctor. CONCLUSION: The population-based trial MEGRE conducted by international methodology in 6 cities of Russia demonstrated that GERD prevalence is 13.3%. Most of the patients pay little attention to the symptoms, do not seek medical advice and, therefore, receive no adequate treatment.

[Use of serum tumor markers in the diagnosis of malignant tumors of the digestive system].

The article is devoted to the main OncoMarkers, which are used in the case of malignant growth in digestal organs, their efficient administration in the medical practise and diagnostic importance.

[Restoration of the quality of life by eliminating and prevention of heartburn by alginate: results of multicenter study "VIA APIA"].

Was conducted a muIticenter study VIA APIA, in which the impact of gaviscon forte (suspension) on symptoms, general state and quality of life of 148 patients (male 53, female 95, age 42.9 +/- 15.6) with gastroesophageal reflux disease (GERD) were investigated. The patients had undergone clinical evaluation of dynamics of GERD symptoms (Likert scale), general state (Visual Analogue Scale, questionnaire SAN) and quality of life (SF-36). It was shown that 14-days treatment with gaviscon forte provided symptoms relief in 84.5% patients and conducted improvement of general state and quality of life. Gaviscon forte recommended as drug of choice in initial treatment for the first time visited patient with heartburn before endoscopy and for pathogenetic treatment of typical reflux syndrome.

[Population demographic structure of the city of Ulan Ude: ethnic composition and age at marriage].

The marriage structure of the population ofUlan Ude, the capital of Buryat Republic, which is characterized by a mixed ethnic composition, has been studied. Differences between Ulan Ude districts in a number of genetic demographic parameters have been found. In ethnic terms, the city district populations differ from one another in the number of ethnic groups and the proportions of the largest groups (Russians and Buryats). In the total Ulan Ude population, the proportions of Russian men and women among persons contracting marriages are 71.44 and 73.79%, respectively; those of Buryat men and women are 23.36 and 22.79%, respectively. The total proportion of all other ethnic groups among both men and women contracting marriages is no more than 5.2%. The mean ages at first marriage in both indigenous and immigrant populations of Ulan Ude are relatively old; these values are 25.9 and 24.72 years for Buryat men and women and 24.86 and 22.69 for nonindigenous men and women, respectively.

[Multicentre study "Epidemiology of gastroesophageal reflux disease in Russia"(MEGRE): first results].

We aimed to determine the prevalence and clinical spectrum of GERD in the urban population of 6 cities in different parts of Russia (St. Petersburg, Ryazan, Kazan, Kemerovo, Krasnoyarsk and Saransk). A previously validated reflux questionnaire developed at the Mayo Clinic was translated into Russian, culturally adapted and administered. Data was collected from 7812 randomly selected subjects greater than 18 years old with the assistance of the yellow pages. 'Frequent symptoms' were defined as a major symptom (heartburn and/or regurgitation) occurring at least once a week or more. "Occasional symptoms" were defined as an episode of one of the major symptoms occurring less than once a week within the past 12 months. Patients were defined as having GERD if they reported frequent heartburn and/or regurgitation. The average prevalence of frequent and occasional GERD symptoms in Russia was 9% and 38.5% for heartburn and 7.6% and 35.3% for regurgitation respectively within the last 12 months. The average prevalence of GERD in Russia was 13.3% (11.3-14.3%). The prevalence of frequent heartburn decreased with age (r = -0.3); however, frequent regurgitation increased (r = 0.7) with age. As a result, we found that prevalence of GERD increased with age. The average prevalence of GERD was statistically the same in men (12.5%) and in women (13.9%). This prevalence didn't change with age in men but did increase with age in elderly women to 24%. Frequent heartburn and regurgitation (GERD) were significantly associated with frequent belching (24.3%), chronic cough (22.9%), dyspepsia (19.8%), non-cardiac chest pain (15.1%), nausea (14.9%), hoarseness (11.4%), dysphagia (8.1%), odynophagia (7.3%) and constipation (37.8%). Alcohol consumption (prevalence of 60.4% among respondents) and smoking (prevalence of 25.4% among respondents) didn't yield any significant difference in subjects with frequent symptoms. Importantly, we also found that only 52.8% of subjects with frequent chest pain and 29.3% of respondents with frequent heartburn had seen a physician for these symptoms.

[Intestinal digestion in patients with chronic pancreatitis].

Clinical signs of a lesion of a small bowel at a chronic pancreatitis are caused by disturbance first of all a membranous stage of intestinal digestion, observed at early stages of disease and progress in process of augmentation of duration of disease. Expression of enzymatic disorders correlated with a lesion of elements of a brush border.

[Prevention of intestinal dysbiosis in patients after anti-Helicobacter therapy].

This article presents a literature review of side effects of antihelikobakter therapy, as well as survey data, whose goal was to determine the efficacy and safety of normoflorins at patients after eradication therapy of peptic ulcer. It was shown that the frequency of occurrence of side effects during antihelikobakter therapy varies widely and can reach, according to different authors, from 30 to 50% of patients. In addition to allergic and toxic PE, with antibacterial agents allocate their influence on the microflora of the colon, which often leads to development of a scarce and dysbacteriosis of antibioticassociated colitis. Appointment of biodiesel of normoflorin after eradication therapy effectively suppresses clinical signs of dyspepsia as a side effect of antihelikobakter therapy enhances the effectiveness of treatment of patients and improve their quality of life.

[Dysbiotic manifestations during eradication therapy of Helicobacter pylori and their corrections].

Forty-eight patients with duodenal peptic ulcer disease infected with Helicobacter pylori were examined. All patients undergo conventional 1-week eradication therapy. After its ending the patients were randomized to two groups: those who will be treated by synbiotics or control group. Normoflorin B and Normoflorin L, which contain bifidobacteria or lactobacilli in complex with different microelements, vitamins, aminoacids, organic acids, and antioxidants, were used as synbiotics. Morphologic study of biopsy samples of small intestine mucosa were performed in patients from both groups. It was determined that eradication therapy worsened existing symptoms of dyspepsia in 80.9% of cases or lead to their emergence, connected with dysbiotic manifestations, in 55.5% of patients. Inclusion of synbiotics in complex therapy resulted in rapid and effective elimination of dyspeptic symptoms, promoted recovery of affected morphologic and functional states of small intestine mucosal epithelium, and optimized metabolic processes important for the digestion.