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Due to the steady increase in the number of children with autism and the high heterogeneity of clinical groups, the diagnosis of these disorders and their severity is an urgent problem in modern medicine. In the course of the work, 126 children from 3 to 13 years old with typical neurodevelopment and with severe and mild autism spectrum disorders (ASD) were examined. Disease severity was determined according to the Childhood Autism Rating Scale (CARS). The levels of pro-/anti-inflammatory cytokines and neurotrophic factors (nerve growth factor beta and brain-derived neurotrophic factor) in blood plasma were assessed by enzyme immunoassay. Associations between indicators in each group of patients were assessed using the Spearman test and visualized as a heatmap of correlations. Statistical data processing was carried out in the R software. Significantly high levels of IL-4 in blood plasma and a decrease in the number of significant correlations within/between systems were revealed in children with mild autism compared with children with typical neurodevelopment. Such data can probably reflect the theory that some children with ASD are characterized by slow brain development, as a variant of the evolutionary norm. On the contrary, in children with severe ASD, high systemic levels of IL-6 and IFNg are shown against the background of low values of IL-10, IL-1β, TNFα and NGFβ, supported by the almost complete absence of intra/ and intersystem interactions. This may act as an indicator of maladaptation of the immune and nervous systems in severe autism, which contributes to the pathogenesis of the disease. Thus, a set of indicators: high levels of key pro-inflammatory cytokines - IL-6 and IFNg, low levels of IL-10, NGFβ and disintegration of the cytokine and nervous systems in the periphery can be proposed as an approach to indicate the severity of the condition in children with ASD.

Chronic low-level inflammation during the aging process is a key risk factor for the activation of resident cells of the brain innate immune system of the (microglia and astrocytes). Such activation leads to the development of neuroinflammation and cognitive impairment which are typical to neurodegenerative diseases such as Alzheimers disease, vascular dementia, Parkinson disease etc. Currently, there is a lack of minimally invasive, affordable methods for diagnosing age-related neurodegenerative diseases and drugs that could slow down or prevent their progression. Hence, a search for new peripheral biomarkers is required, both for diagnostics and monitoring the efficiency of drug therapy. The option of using microRNAs as such biomarkers is under discussion. Our goal was to identify a leukocyte microRNA signature in vascular dementia as compared with healthy aging and reproductive age, in view of inflammation and cognitive deficits. We have examined 54 persons from young to senile age who were classified into the following groups: Vascular dementia, Healthy aging and Reproductive age. Expression of miRNAs known as regulators of communications between the immune and nervous systems (let-7d, let-7g, miR-21, miR-124, miR-146a, miR-155, miR-342-3p) was measured in peripheral blood leukocytes. The decision to study leukocytes was made, since these blood cells are responsible for immune functions, and, especially, cytokine production during aging. Total RNA was isolated by phenol-chloroform technique. The microRNA expression was determined by quantitative polymerase chain reaction with SYBRGreen. The U6 gene of small nuclear DNA was used as a reference housekeeping gene. The differences between groups were determined using the KruskalWallis test with post hoc pairwise comparisons according to ConoverInman. As a result of the study, it was found that the expression of microRNA-21 and microRNA-342 in leukocytes of elderly/senile people, both in healthy aging and in vascular dementia, was increased when compared to the persons in their reproductive age. In the persons with vascular dementia, the expression level of miRNA-124 and miRNA-342 in peripheral blood leukocytes was higher than in healthy aging group. Hence,, microRNA-124 and microRNA-342 may be informative biomarkers for the diagnostics of vascular dementia. However, large-scale studies of their biomarker potential are warranted.

The purpose is to find out the relations of the vascular endothelium dysfunction, atherosclerotic damage to the vessels of the upper and lower limbs, the state of the antioxidant and prooxidant systems, and the lipid profile in patients with different POAG course — carriers of biological clock gene polymorphism.Materials and methods. 47 patients with advanced POAG underwent an examination that included visometry, biomicroscopy, ophthalmoscopy, perimetry, tonometry, thermometry, as well as determination of lipid metabolism, indicators of oxidative stress and antioxidant system. All patients were also tested for the degree of endothelial dysfunction by reactive hyperemia method, and the elastic properties and vascular wall tone by the volumetric sphygmomanometry method. POAG progression was determined by static automated perimetry and optical coherence tomography. The hospitalized patients were examined for daily melatonin profile and key biological clock genes typed by real-time polymerase chain reaction. The genetic material was taken by buccal scraping. Polymorphic variants were identified for CLOCK rs1801260 3111T/C and MTNR1B genes. 16 patients (S-POAG — 8, A-POAG — 8) were tested for melatonin taken from saliva samples at different times of the day in laboratory conditions with controlled nutrition and lighting using the DLMO protocol.Results. The predictors of glaucoma progression were found to be pronounced endothelial dysfunction and oxidative stress, which contribute to the acceleration of atherogenesis and a decrease in the elastic properties of the vascular wall of peripheral vessels. Clock 3111t-c circadian gene polymorphism was found to be interrelated with lipid metabolism disorders and increased lipid peroxidation in patients with POAG progression. Carriers of the G allele of the MTNR1B gene tend to have a higher level of triglyceride (TG) which grows in the evening hours if glaucoma is progressing. We showed that the phasal and amplitude characteristics of daily melatonin level, rather than its average level, may affect the state of the vascular wall of peripheral vessels in POAG patients.Conclusion. POAG progression is associated with pronounced oxidative stress, weakened antioxidant protection and dyslipoproteinemia. Differences in the lipid profile (dyslipidemia) and the indicators of oxidative stress and antioxidant protection in patients with stable and progressing glaucoma course are mutually related with Clock 3111t-c gene polymorphism (CG genotype).

Over last years, the world’s aging populations are rising rapidly, and the phenotypes of cognitive insufficiency, such as old age, depression and dementia, are increasing. Search for approaches to discrimination between such phenotypes is extremely relevant. Current studies present compelling evidence of the key role of immune system (its peripheral compartment), and the stress response system in physiological brain health. Therefore, assessment of complex interactions between immune and neuroendocrine systems may be an effective way to differentiate between depression and early stages of dementia in elderly people. Our purpose was to reveal peripheral molecular messages, e.g., cytokines and stress hormones, in the context of cognitive impairment phenotypes: healthy old age/old age depression/dementia. Eighty elderly people were included into groups as follows: “Healthy ageing”, “Dementia”, “Depression”. Levels of certain cytokines: IL-6, IL-1β, TNFα, IFNγ, IL-10, and stress hormones (cortisol, ACTH, dopamine, noradrenaline, and adrenaline) were determined in blood plasma by ELISA. The intergroup differences were evaluated by the Kruskal-Wallis test with Conover-Inman post-hoc pairwise comparisons. For differential diagnostics between the groups of elderly people with varying grades of cognitive impairment, we used linear canonical discriminant analysis performed on the ranks. It has been shown that cognitive insufficiency phenotypes—old age depression and dementia—differ from the healthy ageing phenotype with their high peripheral levels of TNFα cytokine and low levels of IL-1β. The differences between depression in elderly and dementia included lower level of IL-10 in depression (lower than in “Healthy ageing”), and high IL-6 in dementia (compared to “Healthy ageing”). Evaluation of the hypothalamic-pituitary and sympatho-adreno-medullary axes hormones showed hyporesponsiveness of hypothalamic-pituitary axis, regardless of cognitive insufficiency phenotypes, along with activation of sympatho-adreno-medullary axis, i.e., high dopamine level in old age depression with dementia, and high adrenaline level in dementia, than in depression of elderly phenotype and healthy ageing. Such significant differences in the levels of molecular messages, i.e., cytokines and stress hormones among the old age person groups, enabled diagnostic efficacy of 87.5% to differentiate cognitive phenotypes of aging: healthy ageing, old age depression, and dementia.

Stroke is an acute disturbance of the blood supply to the brain, characterized by the sudden onset of focal neurological symptoms, which persists for more than 24 hours or leads to the death of the patient in a shorter period of time due to cerebrovascular pathology. In the world and in Russia, stroke remains one of the leading causes of death and disability. At the same time, ischemic stroke (IS) is more common – about 80% of cases. Many classes of drugs, such as oral contraceptives, nonsteroidal anti-inflammatory drugs, and various psychoactive substances, can contribute to the development of drug-induced IS (DI IS). Data upon the frequency of DI IS is limited. In part, this reflects the problem of identifying and confirming the causal relationship between drug prescription and the development of IS. DI IS risk factors include: abuse of caffeine and alcohol, older age, smoking, drug addiction, high doses of drugs containing provoking agents, the simultaneous use of several drugs, the presence of comorbid diseases. Adverse drug reactions develop due to the following pathophysiological mechanisms: cerebral embolism, vasoconstriction of cerebral arteries, vasculitis of the central nervous system, orthostatic hypotension. The management of a patient with a DI IS does not differ significantly from the management of a patient with IS of a different etiology and includes thrombolysis or mechanical thromboextraction (in the absence of contraindications), as well as rational methods of secondary prevention. It is necessary to completely cancel or reduce the dose of the drug, the use of which led to the development of a stroke. DI IS prevention measures include the choice of drugs with the lowest risk of its occurrence and the use of modern scales for assessing the risk of this phenomenon.

The study of the small intestine microbiota in humans is difficult due to the low availability of biomaterial. Non-invasive methods of metabolomics and bioinformatic data analysis can expand our understanding of the structure and role the small intestine microbiota in maintaining homeostasis of the body. The article presents the trajectory of age-related changes in the microbial community of the small intestine in healthy individuals in the context of interaction with the cytokine and neuroendocrine systems within the metaorganism, using the methods of gas chromatography - mass spectrometry of microbial markers (GCMS MM) and optimal scaling. 110 practically healthy individuals: children, adults and elderly, were included into the study. The number of the main types of small intestine microbiota ( Bacteroidetes, Firmicutes, Actinobacteria, Proteobacteria, and Fusobacteria ) was determined in peripheral blood by the GCMS MM method. To construct the trajectories of changes in the small intestine microbiota and indicators of the cytokine and neuroendocrine systems with age, the optimal scaling technique based on the multivariate Gifi transformation (CATPCA method) was used. It was found, that the bacterial community of the small intestine of both children and the elderly and seniors has a significantly low total number of microorganisms, due to the low content of bacteria of the types Firmicutes and Actinobacteria against the background of a high number of representatives of the types Proteobacteria and Fusobacteria , in comparison with similar indicators in adults. Assessment of the trajectory of age-associated changes in the microbiota of the small intestine showed: 1) children have strong dynamic fluctuations in the number and connections within the community of microorganisms against the background of the formation of connections between the main regulatory systems of the metaorganism – immune and neuroendocrine; 2) adults present the plasticity and consistency of the functioning of the immune and nervous systems, what determine the state of dynamic balance of the small intestine microbiota; 3) healthy aging characterize by hight degree of cooperation between the main members of the bacterial community, which ensures the stability of the system at a new level, as one of the mechanisms of adaptation of the organism. Thus, the using the methods of GCMS MM and optimal scaling, allows us to expand our understanding of the age-associated trajectory of changes in the small intestine microbiota and its cooperation with the immune and neuroendocrine systems within the metaorganism, which can be used in the development of new methods of therapy of an infectious and non-infectious diseases.

Currently, differentiation between autism spectrum disorders and schizophrenia spectrum disorders in children is a difficult task, because it relies mainly on behavioral and symptomatic characteristics, since these disorders are highly similar. We have previously demonstrated that peripheral indexes of immune and neuroendocrine systems, which we combined into cytokine-neuroendocrine signature, may reflect distinct clinical phenotypes of autism and schizophrenia spectrum disorders. Moreover, a number of researchers discovered the “accelerated ageing” phenomenon in the persons with schizophrenia, which includes deficiencies of cognitive functions and performance as the main symptoms. Here we carried out a search for biological markers of the “accelerated ageing” phenomenon in children with autistic conditions and schizophrenia spectrum disorders. Our aim was to assess the opportunity of applying the cytokine-neuroendocrine signature as biological evidence of “accelerated ageing” phenomenon in children with autism and schizophrenia spectrum disorders, which could be potentially useful for differential diagnosis of these disorders.Thirteen parameters of the cytokine-neuroendocrine signature were assessed in blood plasma using ELISA method in 82 children with autism, 9 children with schizophrenia, 45 normally developing children, 25 subjects in their reproductive age, and 39 elderly persons: cytokines (IL-6, IL- 1β, IFNγ, TNFα, IL-10, IL-4) and neurohormones (oxytocin, dopamine, adrenaline, noradrenaline, adrenocorticotropic hormone, cortisol, and serotonin). The nonlinear principal component analysis (CATPCA algorithm) was used to assess the variants of cytokine-neuroendocrine signature for different diagnostic categories, i.e., “autism spectrum disorders”, “schizophrenia spectrum disorders”, and “healthy ageing”.The “healthy ageing” variant of cytokine-neuroendocrine signature presented a classic phenomenon, referred to as immune senescence presented by pro-inflammatory age-related cytokines — IL-6, IL- 1β, IFNγ. Only the “schizophrenia spectrum disorders” variant of the cytokine-neuroendocrine signature, unlike all the other signature variants, demonstrated high-level similarity with the “healthy ageing” variant (differing in 2 out of 13 indexes): lower levels of IL- 1β and IFNγ, at the same level of IL-6 “gerontological cytokine” index.Evaluation of the cytokine-neuroendocrine signature can be used for differentiation between autistic disorders and schizophrenia spectrum disorders, including predictive diagnostics in children with autism, thus enabling group selection of children at risk for later conversion to schizophrenia.

Purpose: to study the antioxidant system and lipid status of serum and evaluate the effect of Cytoflavin on these characteristics in patients with progressive and stable primary open angle glaucoma (POAG).Patients and methods. 67 patients with advanced stage POAG were observed. The average age was 66.3 ± 1.5 years. According to the course of the glaucoma process all patients were randomized into 2 groups: the 1st group with the stable glaucoma (31 patients) and the 2nd group with rapidly progressive glaucoma (36 patients). The progression criteria of POAG were global ganglion cell loss volume (GLV) and perimetric index (mean deviation-MD). For assessment of the reactivity of the vascular endothelium, a test with reactive hyperemia was performed using ultrasound method. The assessment of oxidative stress (OS) including peroxides, malonyldialdehyde (MDA) and the total antioxidant capacity of serum (AOS) were evaluated. The investigations of lipid metabolism included the level of cholesterol total (CT), cholesterol of low-density lipoproteins cholesterol (LDL-C), high-density lipoproteins cholesterol (HDL-C), triglycerides (TG) and atherogenic index (AI).Results. In the 2nd group there was the significant decrease of the mean GLV indices compared to those in the 1st group (7.16 ± 2.5 и 1.06 ± 0.2, respectively, р < 0.001). The mild degree of endothelial dysfunction (ED) predominantly was detected in patients of the 1st group (69 % of cases). The moderate and marked ED were found in patients with progressive POAG (68 and 25 %, respectively). The high level of OS in serum was determined in 43 % of patients of the 1st group and in 69 % of patients of the 2nd group (significant increase of peroxides and MDA). In patients with progressive POAG the mean indices of lipid metabolism (CT, LDL-C, HDL-C, TG, AI) were significantly higher than in healthy subjects (р < 0.001). Cytoflavin had a positive effect on the vascular endothelium function, normalization of lipid metabolism and decrease of OS in serum with increasing AOS in patients with progressive POAG.Conclusion. The assessment of the indices of OS, AOS and lipid metabolism enable us to determine the risk of progression of POAG and evaluate of the effectiveness of treatment.

Literature data have shown the shortcomings of current domestic and foreign registers of glaucoma patients: none of them provides adequate monitoring and prognostication of the disease. The study presents the main tasks, principles and methodological foundations of building a regional glaucoma register — an automated system for collecting, storing and processing information on glaucoma patients living in the Tyumen region. Requirements for organizational, informational, software and technical support of the register are given. The stages of register development are described in detail, including the issues identified during the use of the database and the ways to solve them. The work highlights the steps already taken to develop and implement a regional glaucoma register and discusses the prospects for further development of this area in health care management, aimed at improving the quality of medical care. The data will help clinicians in the development of similar databases in other regions of Russia, as they highlight the difficulties that may occur. The possibilities of solving other topical research issues, in particular the efficacy and safety of pharmacotherapy of disease progression, are discussed. The regional glaucoma register can serve as a tool for providing high-quality diagnostics, treatment and observation of patients with glaucoma and a possible model of the future National Register across Russia.

The expansion of viticulture in the world is accompanied by the spread of diseases and plant pests. Phylloxera is one of those organisms causing enormous damage to the world’s viticulture. The discovery of the possibility of grafting varieties on stock has led to the development of the breeding of stock originating from North America. Currently, the active use of different types of molecular markers for the identification and study of the genetic diversity of grapes allows to more accurately and efficiently study the biological peculiarities and genetics of plants. Obtaining good reproducibility of the analysis results and revealing the polymorphism between varieties and clones when using different types of markers, you can further use this knowledge for breeding in the selection of crossed pairs. The aim of the study in the present article was to study the common stock grape varieties - hybrids of American species. The article presents a study of the five most famous stock grape varieties: Kober 5BB and 420-A, Paulsen 1103, 101-14 and Richter 57 to identify genetic relationships and polymorphism between samples, based on the use of IRAP and iPBS primers. We used thirteen selected DNA markers that generated a total of 308 polymorphic DNA bands with 54.95 % polymorphism. The effectiveness of iPBS markers was comparable or even more effective than the markers based on retrotransposons. As a result of research, differences and commonality between stocks were clearly demonstrated by both cluster analysis and PCoA analysis.

Here we present the data on examining inter-connections cytokine network and stress hormones in senile vascular dementia by assessing systemic cytokine levels for IL-1β, IL-6, IL-10, TNFα, IFNγ as well as hormones cortisol, adrenocorticotropic hormone (ACTH), epinephrine, norepinephrine and dopamine in 23 subjects with vascular dementia and 40 individuals without overt cognitive impairment. It was found, that the concentrations of IL-6, TNFα, epinephrine and dopamine were significantly increased, whereas those for IL-1β, IL-10, ACTH and norepinephrine were decreased in elderly people with dementia compared to healthy aging. In addition, virtually no inter-connection between cytokine, sympathoadrenal and hypothalamicpituitary (HPA-axis) axis was observed in vascular dementia highlighted by no significant correlation within the cytokine network. However, a single positive intrahormonal link for cortisol-ACTH and two positive links between IFNγ and cortisol/adrenaline level were detected. In general, vascular dementia was featured by marked inflammatory reaction, excessive activation of stress hormone production and disconnection of cytokine network, HPA-axis and the sympathoadrenal medullary system.

Plant-derived medicinal products provide a prominent advantage due to their low toxicity to humans and combined effects of biologically active substances, mainly presented by polysaccharides, flavonoids and terpenoids. One of the mechanisms undedrlying effects from medicinal plants on the immunoregulationrelated events is mediated via controlled production of certain cytokines. Here we examined immunoregulatory activity of water extracts derived from medicinal plant raw materials (LRS) containing polyphenolic compounds – flavonoids (rutin, quercetin, called P-vitamins). The aim of the study was to assess profile and level of cytokines secreted by human peripheral blood mononuclear cedlls exposured to flavonoid-containing LRS water extracts. LRS (1:10) water extracts of the following species were used: black currant leaves (Ribes nigrum L.), field horsetail grass (Equisetum arvense L.), common yarrow grass (Achillea millefolium L.), licorice roots (Glycyrrhiza uralensis Fisch.), sand immortelle flowers (Helichrysum arenarium (L.) Moench), wild strawberry leaves (Fragaria vesca L.), fruit common bird cherry (Padus avium Mill.), tansy flowers (Tanacetum vulgare L.) and oat grass (Avena sativa L.) (all purchased at the pharmacy). Production of pro – (TNFα, IL-8, IL-1β) and anti-inflammatory (IL-10) cytokines was measured by using ELISA kits (“Cytokine”, Russia) in mononuclear cell culture supernatant treated with / without LRS (experiment and control group, respectively). Amount of flavonoids contained in flowers and leaves was quantified aftedr complexation reaction with aluminum chloride on UV-3600 spectrophotometer (Shimadzu, Japan). It was found that LRS water extracts predominantly inhibited production both of pro- (TNFα, IL-8, IL-1β) and anti-inflammatory (IL-10) cytokines so that magnitude of such suppressive effect ranged from 51.5±3.4 to 99.5±4.1% compared to untreated control samples (p 0.05). Total flavonoid level in the LRS samples diirectly correlated with intensity of related immunoregulatory activity on cytokine secretion particularly TNFα (r = 0.65), IL-8 (r = 0.4), IL-1β (r = 0.48) and IL-10 (r = 0.68). The data of our study allow to conclude that extracts from the examined medicinal plant raw materials can be considered as promising components while developing new drugs with exhibiting immunoregulatory and antiflogogenic effects.

The work is devoted to the study of peculiarities of the hereditary potential of soft winter wheat productivity in the conditions of the Belgorod region. The study of yield of winter wheat varieties was conducted for two years. In 2016, 8 varieties zoned in our (fifth) region of this culture of breeding of the Belgorod and Kursk regions and 8 of other origin were studied. It is established that the yield in the first group of varieties made up of 5.31 t/ha, and in the second group it is 3.76 t/ha [(the Least Significant Difference) LSD 0.95 = 0.73 t/ha]. In 2017 continued the test. The second group, of southern origin, included 15 varieties. The following results were obtained: the first group had a yield of 6.45 ±0.24 t/ha and the second of 4.64 ±0.68 t/ha (t = 6.08***, p < 0.001). In the second group were the varieties approved for use in our region (4 varieties from 15) and rated their productivity. Their productivity made up 4.92 ±0.41 t/ha. The difference from the first group was 1.53 t/ha, which was statistically significant (t = 3.21*, p < 0.05). The obtained data confirm the results of varietal groups estimations yield for previous years (2008-2010). In this case, the group of Krasnodar-Zernograd varieties (4) breeding had an average yield of 3.25 t/ha for three years, 3.00 t/ha was of the Moscow origin (2), and varieties created in the Belgorod area (5) were un yield of 4.39 t/ha. Presented data indicate the need to expand breeding work in regions of the Russian Federation, which will allow more efficiently use of the potential in winter wheat culture. The positive temperature dynamics in recent years has not increased the adaptability of varieties of southern origin to the conditions of the Belgorod region.

One of the main places in the selection of grapes today belongs to native varieties. Native varieties possess characteristics valuable in economic relations, such as a high-quality berry crop, from which it is subsequently possible to obtain the highest quality wine, as well as resistance to harsh climatic conditions. However, before starting breeding work, it is necessary to conduct various pre-breeding studies, including genetic analysis. This type of analysis is the most informative of all, because it gives the most complete picture of all the genetic predispositions of any organism, as well as what potential the specific varieties possess. The analysis is carried out using a variety of molecular genetic markers, which include IPBS markers. The mechanism of their action is based on the use of primers for PBS retrotransposon sequences (Primer binding site, tRNA binding site). This choice is due to the fact that IPBS markers perform well when detecting polymorphism between samples, which include both varieties and clones of varieties. As a result, the following DNA markers were used: iPBS2074, iPBS2230, iPBS2415, Vine-1, and the following indigenous grape varieties: Kumshatsky, Varyushkin, 9th row of class 19, Chilyaki 1-23 (35-36), Cinnamon white mutation, Slitny, Decent , Augustine, Yay raisin white, Kishmish oval white, (Sultanina), Yay raisin pink, Kishmish red Turkmen (Sultatnina pink), Tsimlyansky black. Based on the results of all the studies, namely polyacrylamide gel electrophoresis (PAGE), interpretation of the obtained photos, and subsequent data processing in Microsoft Excel using the GenAlEx 6.3 macro, analysis in AMOVA, and MEGA7 with UPGMA parameters, the conclusions were made that molecular markers of IPBS were effective in preselection studies of the native grape varieties.

According to the results of land assessment, the cadastral value of agricultural land in Tyumen oblast varies from 2900 rubles per hectare for peat-podzolic soils to 69 300 rubles per hectare for ordinary chernozems. The development of solodic and solonetzic processes decreases the cadastral value of chernozems by 50 to 90%. The cadastral values of podzolic, soddy-podzolic, and gray forest soils do not exceed 10 000 rubles per hectare. The cadastral value of meadow-chernozemic and meadow soils is 41 200 and 25 700 rubles per hectare, respectively. A sensitivity of the cadastral value estimation approaches to different soil-geographical conditions is demonstrated.

The polymorphism of beta-amylase isoenzymes in spring common wheat was studied among varieties cultivated under the conditions of the Northern Trans-Urals. Four zymotypes were identified among the 41 accessions. A, C, and A* isozymes differed most frequently, the share of which, respectively, was 64.6 ± 7.3, 22.0 ± 3.7, and 12.2 ± 3.7%. During 2011–2013, the aggregating ability of grain proteins was studied using -S-S-bonds between groups of varieties carrying variants of beta-amylase A and C. It was established that the presence of isoenzyme C promoted a greater aggregation of grain polypeptides in comparison with beta-amylase A carriers but did not affect the formation of yield. Differences in beta-amylase did not affect the falling number associated with amylase activity.

Aim. To study the multimorbid features in the long-lived veterans of the Smolensk region. Material and methods. One hundred and twelve patients (male =58, female =54) aged ≥90 years who were hospitalized and rehabilitated at the Smolensk Regional Clinical Hospital for War Veterans during the period of 2013-2015 was surveyed. We studied previous diseases, multimorbidity index. Blood pressure was measured daily for all patients. The criteria for arterial hypertension were considered blood pressure >140/90 mm Hg. or regular use of antihypertensive drugs. All patients get a clinical blood analysis, routine electrocardiography, Holter recording if medically required. We determined total cholesterol, triglycerides, glucose, alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, total protein, bilirubin, creatinine, urea serum (analyzer — STAT FAX “USA”). Results. The results of the study demonstrated: disability at the age of >60 years old, low multimorbidity index (

A large and diverse repertoire of antibodies encodes the history of past immunological experience, creating a global network of the body’s regulation system. In this article, we propose to use a peptide microarray (“immunosignature”) for evaluating global individual antibody patterns and bioinformatic data analysis for differential diagnosis of autism spectrum disorders. The peptide microarray consists of 124 000 antigen mimetics with random sequences covalently bound to the surface of the glass slide. A drop of plasma is tested for the presence of antibodies of distinct specificity, by measuring their binding to each antigen mimetic in the microarray detectable by fluorescent staining with secondary IgG antibodies, and this reaction is registered by laser activation assay. For bioinformatic analysis, we used the files of digitalized fluorescence intensity data, which presented the reactivity of plasma antibodies bound to antigen mimetics. Data processing was carried out by packages of the Bioconductor project for the R software environment to perform statistical evaluation. At the stage of primary data processing, the quantile normalization was used in order to equalize the distributions of antibodies’ reactivity. The sample data and other necessary information were combined into the discrete ExpessionSet container files. To compare the control and experimental groups, the Welch’s one-way ANOVA (for unequal variances) was used. The obtained estimates of the mean value differences and statistical significance of P levels were used further for constructing a volcano diagram, in order of ranking and selecting the most promising antibody reactivity parameters. For differential diagnosis of autism, and evaluation of diagnostic significance of the immunosignature method, a heatmap was constructed. The standardized values of the logarithms of antibody reactivity, and the results of the hierarchical cluster analysis performed by the Ward method using Pearson correlation, as a measure of similarity were used in constructing the heatmap. As a result of the bioinformatiс analysis of the data, 73 antibodies were selected whose reactivity had statistically significant differences in groups of children with autism and normally developing children. These antibodies were used for differential diagnosis, the value of which was determined in the heatmap construction. It was found that the group of children with autism spectrum disorders by the antibody reactivity exhibits marked heterogeneity, and consists of at least two subgroups. In addition, 60 antibodies in children with autism showed predominantly medium and low reactivity, i.e. these antibodies had a weak binding power with antigenic mimetics, and only 13 antibodies showed high reactivity. In general, diagnostic specificity of the autism spectrum disorders using immunosignature approach was 96.0% (95% CI 82.8 to 99.6%), sensitivity was 78.3% (95% CI 64.9 to 88.2%), and diagnostic efficiency was 82.7%. Our pilot study allows us to propose a method of immunosignature for differential diagnosis of autism and, possibly, to expand our understanding of autism spectrum disorders.

Сomplex intergenic interactions should be taken into account when predicting the risk of adverse course in a pathological process. This presumption is at the heart of evolving multifactorial diseases (ulcerative colitis and irritable bowel syndrome). A single genetic polymorphism seems to be a weak risk factor when predicting the disease evolution and it could not be used as a prognostic model for development of multifactorial pathologies, especially in cases of rare alleles. However, it is well known that the combination of unfavorable alleles of several genes with an additive effect is dangerous. Therefore, identification of such polymorphisms is very important.Previously we conducted a test panel, in order to evaluate associations of alleles and genotypes of some cytokine genes (IL1β, TNFα, IL1rа, IL10, IL6) with predisposal, or resistance for ulcerative colitis and irritable bowel syndrome in the Russian Chelyabinsk region. Distribution of alleles and genotypes of these genes have been assessed in irritation bowel disease (IBD) and ulcerative colitis (UC). The following methods were used: isolation of DNA samples from whole blood, genotyping of the studied gene polymorphisms with PCR, RFLP. A comparative analysis of intergenic interactions between the cytokine genes IL1β, TNFα, IL1ra, IL10, IL6 in the IBD and UC patients was carried out by the Multifactor Dimensionality Reduction method. The analysis is based on the use of polymorphic loci of IL1β, TNFα, IL1ra, IL10, IL6 combinations chosen for analysis of intergenic interactions, with respect to the risk for IBS and UC predisposition. As a result of this study, a fourlocus model IL1β(+3953)*Т/TNFα(-308)*A/IL10(-1082)*G/IL6(-174)*G was identified for IBS, which was characterized by 90% repeatability and prediction accuracy of 74.5%. This model of gene interactions between the cytokine IL1β, TNFα, IL1ra, IL10, IL6 genes had the greatest prediction potential (p < 0.001) in IBS, whereas the model for UC was not statistically significant. The following types of genetic interactions were established: synergism between the IL1β(+3953)*Т and TNFα(-308)*A loci, whereas IL6(-174)*G и IL10(-1082)*G, TNFα(-308)*A seem to be in antagonistic relationships. The study made it possible to establish that the -174G/C IL-6 polymorphism may play a central role and provide intergenic interactions with SNPs of IL1β, TNFα, IL10 for predisposal to irritable bowel syndrome in Chelyabinsk Region of Russia.

Aging and genetic predisposition are major risk factors in age-related neurodegenerative disorders. The most common neurodegenerative disorder is Alzheimer's disease (AD). Genome-wide association studies (GWAS) have identified statistically significant association of the PICALM rs3851179 polymorphism with AD. The PICALM G allele increases the risk of AD, while the A allele has a protective effect. We examined the association of the PICALM rs3851179 polymorphism with parameters of the P3 component of auditory event-related potentials (ERPs) in 87 non-demented volunteers (age, 19-77 years) subdivided into two cohorts younger and older than 50 years of age. We found statistically significant association between the AD risk variant PICALM GG and increase in the P3 latency in subjects over 50 years old. The age-dependent increase in the P3 latency was more pronounced in the PICALM GG carriers than in the carriers of the PICALM AA and PICALM AG genotypes. The observed PICALM-associated changes in the neurophysiological processes indicate a decline in the information processing speed with aging due, probably, to neuronal dysfunction and subclinical neurodegeneration of the neuronal networks in the hippocampus and the frontal and parietal cortical areas. Such changes were less pronounced in the carriers of the PICALM gene A allele, which might explain the protective effect of this allele in the cognitive decline and AD development.

Aim. To assess the structure of the intestinal microbial consortium and the level of oxytocin in blood plasma in the context of severe social insufficiency in children with autism spectrum disorders. Materials and methods. 44 children with autism spectrum disorders were divided into two groups: 23 children with no signs of social contact and 21 people with preserved social contact. The comparison group was consisted of 39 typically developing children of the appropriate gender and age. The structure and quantity of microorganisms of the small intestine was determined with the help of specific lipid markers in peripheral blood by gas chromatography-mass spectrometry of microbial markers. The concentration of oxytocin was assessed in plasma by the method of ELISA. Results. Normally, the biochemical signals of the ecological system (the host-associated microbial consortium and the neuropeptide-oxytocin) work in the general context of the socialization of the meta-organism. However, an imbalance of the system (disease - autism spectrum disorders) can lead to change context and social insufficiency. Conclusion. Research in this direction will help, as we believe, to understand of the mechanisms underlying social deficits in autism, which will allow us to determine the ways of their correction.

Aim. Detect connection between cognitive dysfunction in senior people with systemic infection profile and small intestine microbiota structure. Materials and methods. 42 senior individuals were included into the study All the examined have been divided into 2 groups based on the results of psychic status: 20 individuals with moderate cognitive disorders - «active longevity» group and 22 individuals with pronounced cognitive deficiency - «mercy» group. Systemic inflammation status and structure and quantitative composition of microbiota of small intestine was determined in all the senior individuals using gas chromatography mass-spectrometry of microbial markers. Results. Interconnection between systemic level of cytokines and microbiota structure of small intestine in senior people with various cognitive status was determined. Significant correlations between levels of pro-inflammatory cytokine IL-6 in blood plasma and quantity of Propionibacterium jensenii, Moraxella spp., Bacillus cereus and Fusobacterium spp. in small intestine and the degree of cognitive failure were detected for the first time. Conclusion. The parameters obtained could be used as predictive biomarkers of cognitive dysfunction in senior people.

Secondary metabolic myopathies develop in endocrine pathologies, different somatic diseases, electrolyte disorders and in some vitamin deficiency. Myopathic syndrome caused by vitamin D deficit is a rear pathologic condition, for this reason it is difficult to diagnose it. Proper diagnosis has a vital importance for proper treatment choice. The article describes a rear form of the metabolic myopathy in a young female admitted to the neurology department because of significant leg weakness. A thorough examination revealed no pathology of internal organs. On physical examination moderate lower flaccid paresis with reduced tendon reflexes was revealed. Muscle tone was normal. The absence of systemic inflammatory changes in blood tests as well as normal biopsy results ruled out dermatomyositis and polymyositis. Blood tests revealed deficiency of 25-OH-vitamin D. On vitamin D monotherapy leg weakness completely resolved. In case of myopathic syndrome it is necessary to have in mind such rear causes for its development as vitamin D deficiency.

A formalized approach is proposed to evaluating design loads on shovels with compound kinematic chains, based on numerical estimates of response of primary structural members to unit forces. The practical implementation of the approach uses structural layout of a mine shovel with electromechanical pushbars of pressure and uplift drives.

From the point of view of dynamics, structural damage manifests as a decrease of stiffness of the material of structural elements or a decrease of their masses (removal from the system due to destruction). The effect of damage on the behavior of vibration systems consists in redistribution of stiffnesses and masses and manifests as a change in natural frequencies and vibration modes. The survivability of damaged vibration systems is viewed as the sensitivity of their natural frequencies and vibration modes to various types of damage. The survivability analysis technology consists in a multivariate modal analysis of the structure with variation in its damage. The article considers the results of numerical simulation of frequencies and modes of natural vibrations of a high-pressure xenon tank mounted on the hull’s primary structure after various types of damage to the latter. The tank is a part of the electric propulsion engine of a spacecraft. The results allow assessment of the sensitivity of dynamic characteristics of the tank to damage to the primary structure.

To study the reactivity of the vascular endothelium and the elastic properties of the upper and lower extremities, and assess the vascular innervation effect of Cytoflavin in patients with stable and rapidly progressive primary open-angle glaucoma (POAG).The study included 67 patients with POAG (mean age 66.3±1.5 years), among them 31 with stable and 36 with rapidly progressive glaucoma. During the first stage of the study, the reactivity of the vascular endothelium was assessed with reactive hyperemia test; the viscoelastic properties of the upper and lower extremities were evaluated using volumetric sphygmomanometry. For the second stage of the study, patients were divided into the main group (The function of the vascular endothelium was significantly reduced in patients with rapidly progressive POAG. Correlation analysis revealed a negative correlation between the flow-dependent vasodilation (FDV), and the duration of POAG and initial diameter of the brachial artery (The obtained data can be used for identification of risk factors for rapid POAG progression and optimization of its treatment.Изучить реактивность сосудистого эндотелия, упруго-эластические свойства и состояние тонуса сосудов верхних и нижних конечностей, а также вазорегулирующее действие Цитофлавина у пациентов со стабилизированным и быстропрогрессирующим течением первичной открытоугольной глаукомы (ПОУГ).Обследовано 67 пациентов с ПОУГ (средний возраст— 66,3±1,5 года), из них 31 пациент — со стабилизированным течением и 36 пациентов — с быстропрогрессирующим течением заболевания. На первом этапе исследования оценивали реактивность сосудистого эндотелия с использованием пробы с реактивной гиперемией; упруго-эластические свойства и тонус сосудов верхних и нижних конечностей определяли методом объемной сфигмоманометрии. На втором этапе пациенты были разделены на две группы: основную (Выявлено достоверное ухудшение функции сосудистого эндотелия при прогрессировании глаукомы. С помощью корреляционного анализа определена отрицательная достоверная зависимость поток-зависимой вазодилатации (ПЗВД) от длительности течения ПОУГ и исходного диаметра плечевой артерии (Полученные данные могут использоваться для определения факторов риска прогрессирования ПОУГ и оптимизации терапии заболевания.

The aim is to assess the levels of certain cytokines IL-6, TNF-α, IL-1β и IL-10, and BDNF in the blood plasma of the elderly, depending on degree of cognitive impairment. 65 elderly with (vascular dementia) or without cognitive impairment were enrolled in the study. The level of cytokines and BDNF were measured in plasma by ELISA. It was found that, regardless of the degree of cognitive impairment, the condition of systemic chronic low-grade inflammation is characteristic of the elderly. Against this background, plasma levels of BDNF were increased in elderly with vascular dementia, reaching statistical significance compared with healthy individuals. Such changes in the level of BDNF may reflect a compensatory repair mechanism in neurodegeneration or be associated with a defective axonal transport or utilization of BDNF in the central nervous system paralleled by increased serum concentrations.

This paper deals with design values of safety factors for load-bearing reflector skeleton made of polymer composites. These safety factors characterize the strength, stability and geometry constancy of the reflector in a wide range of mechanical and thermal impacts.

This work is devoted to analysis of deformation and destruction of structurally heterogeneous joint assembly. The mathematical formulation of interacting parts of joint assembly is investigated. Logical and computational model of joint assembly presents various modes of its destruction and describes impairment conditions because of different damage states.

The methodology and methodological approaches to research on mental health in relation to quality of life and data of subjective health status assessment are presented. The research was performed over a period of 2004-2011. Medical social monitoring data were obtained for a total of 3975 people living in the protective actions zones of chemical weapons storage and destruction facilities in three administrative regions. Qualitative assessment of satisfaction with various aspects of life, taking into account the specificity of potentially facilities was performed. Correlations of the quality of life and the self-rating of health with the factors affecting human health are established. Almost half of the population under study (47.1 %) wasfound to require supervision and treatment by specialists in boundary psychiatry and mental medicine. It was found that negative effects of human health are multifactorial, and the contribution of each individual factor in the immediate and delayed the deterioration of somatic and mental health, associated with the quality of life, is quite difficult to quantify.

Alkylation of 4(5)-nitro-1,2,3-triazole with alcohols in concentrated H2SO4 occurs at all three endocyclic N atoms, giving a mixture of isomeric N(1)-, N(2)-, and N(3)-alkyl-4-nitro-1,2,3-triazoles (alkyl is isopropyl, sec-butyl, and cyclohexyl). The selectivity of the alkylation depends on the alcohol used. The most selective alkylation is provided at the N(2) atom when isopropyl (81%) and sec-butyl alcohols are used (67%). With an increase in the reaction time, also in the order isopropyl-, sec-butyl-, and cyclohexyl-4-nitro-1,2,3-triazoles, the N(2)-isomers undergo isomerization into N(1)-alkyl-4-nitro-1,2,3-triazoles. In all the cases, the fraction of the N(3)-substitution products in the mixtures is 6–30%.

The product of substitution at the nitrogen atom N(4) is found along with main N(1)- and N(2)-substituted 5-R-3-nitro-1,2,4-triazoles among the products of 5-R-nitro-1,2,4-triazolate anion (R = H, Me, Et) reactions with diethyl sulfate in aqueous medium. The fraction of 5-R-4-ethyl-3-nitro-1,2,4-tri-azoles, which varies from 1.3 to 6.9%, depends on the temperature, ratio of the starting reagents, and the degree of the alkylating agent consumption.

Results of the study in three regions of the Russian Federation have shown widespread of high carcinogenic human papillomavirus among patients of dermatovenerological and gynecological profile. Detection of viral DNA in the material from the cervix and urethra ranged from 25,2 (Karelia) to 42,5 (Sakha Republic (Yakutia) per 100 examined patients. In all areas in 2010-2011 first place was occupied by 16-th virus genotype - from 11,5 (Sakha Republic (Yakutia) to 15,9 (St. Petersburg) per 100 patients. Prevalence of 11 other types differs. In the Sakha Republic (Yakutia) the second rank place was occupied by types 31 and. 51 (8,0 per 100 examined patients), in St. Petersburg - by 56 and 31 types (9,7 and. 7,6 per 100 patients). Age risk group contains patients of the age of 20-29 years. Information on circulating genotypes of the virus is a necessary part of surveillance to validate vaccination against human papillomavirus infection and evaluation of its efficiency.

The process of alkylation of 1-alkyl-substituted 4-nitro-1,2,3-triazoles with dimethyl and diethyl sulfates has been studied. The structures of the N,N’-dialkyl-C-nitro-1,2,3-triazolium alkylsulfates and perchlorates has been confirmed by IR, 1H and 13C NMR spectroscopy. Alkylation with an excess of dialkyl sulfate occurred regioselectively at N-3 with the formation of 1,3-dialkyl-4-nitro-1,2,3-triazolium salts, which is in agreement quantum-chemical calculations of the relative stability of the corresponding isomeric cations. The molecular and crystal structures of the first example of this type of salt – 1,3-diethyl-4-nitro-1,2,3-triazolium perchlorate – have been determined by X-ray crystallo-graphy. Nitrotriazolium salts with mixed alkyl substituents – 3-ethyl-1-methyl- and 1-ethyl-3-methyl-4-nitro-1,2,3-triazolium salts – have been synthesized an studied for the first time.

Parameters of physical development, the cardiorespiratory system, and physical fitness were studied in female athletes aged 9–22 years. It was found that sports aerobics affects profoundly the functional capacity of the muscular and cardiorespiratory systems and, to a smaller degree, the morphological characteristics of the body.

The alkylation of the title compounds occurs at all three endocyclic N-atoms leading to a mixture of N(1)-, N(2)-, and N(3)-alkyl-4-nitro-1,2,3-triazoles.