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There has been developed and validated the technology for massive parallel sequencing for the purpose of molecular genetic diagnosis of hereditary glycogen storage diseases. Among 96 patients aged of from 15 months up to 18 years, the diagnosis was verified in 89 (92.6%) children. Glycogen storage disease (GSD) type IX appeared to be the most frequent form of glycogenosis in children, diagnosed in 29.3% of cases, GSD type IV, verified in 1.1% of cases, was a rare form of glycogenesis. In 39 (43.8%) out of 89 genetically confirmed children, there were revealed 35 (44.3%) of the previously undescribed mutations from 79 pathogenic variants found in 9 (45%) of different genes of 20 examined cases, indicating to a significant heterogeneity of genetic factors of the development of GSD in the Russian population. Mutations c.247C>T of the G6PC gene, c.1042_1043del of the SLC37A4 gene, c.3980G>A and c.1423+1G>A of the AGL gene, c.-32-13T>G of the GAA gene, and c.884G>A of the PHKA2 gene were been established to be characteristic for the Russian population of GSD children. There was shown the high sensitivity and specificity of the massive parallel sequencing for the search for single nucleotide substitutions in coding and adjacent intron regions, as well as small deletions and duplications of genes, mutations in which lead to the development of GSD. Massive parallel sequencing is necessary for the rapid diagnosis of GSD, timely appointment of the adequate treatment, prevention of complications, which will improve the quality of the life of GSD patients.

Treatment of the glycogen storage disease (GSD) type I with uncooked cornstarch (UCS) allows to maintain long-term normoglycemia, however, the efficacy of the treatment declines due to the insufficient compliance of children patients and their parents. There were determined clinical and laboratory features of the course of GSD type I in children on the long-term comprehensive therapy. There was performed a retrospective analysis of case histories data on 19 GSD children, including 8 patients with subtype Ia and 11 cases - with subtype Ib. All children received the treatment with both UCS and hepatoprotectors. It was established that during the treatment liver sizes did not change significantly, the fasting blood glucose concentration increased by 2.8 times to 4.21 mmol/l, lactate content decreased by 1.9 times to 5.1 mmol/L, ALT activity decreased by 2.5 times, AST - by 3.3 times, and GGT - by 1.8 times if compared to the level before the treatment. In children with GSD subtype Ib blood concentrations of triglycerides prior to the treatment were 2 times higher than baseline values andfailed to change on the comprehensive therapy. Blood levels of cholesterol and uric acid after the treatment also were not significantly dependent on the duration of the therapy. The authors suggest that comprehensive course therapy of GSD type I by means of prescription to children UCS in combination with hepatoprotectors contributes to the compensation of carbohydrate metabolism and provides the relief of cytolysis and cholestasis, but disturbances of the purine and lipid metabolism in patients persist.

Tyrosinemia type 1 (OMIM 276700, E70.2) is a rare hereditary form of the disorder of metabolism caused by the deterioration of tyrosine metabolism emerging due to pathological change in the reference sequence of the FAH gene coding fumarylacetatoacetate hydrolase. The reduced activity of this enzyme leads to the accumulation of a maleylacetoacetate, fumarylacetatoacetate and their derivatives: succinylacetatoacetate and succinylacetone which exert toxic effect on tissues of human body especially on liver and kidneys cells. Implementation of the method of tandem mass-spectrometry allowed to carry out early screening diagnostics of tyrosinemia type 1 in dry blood spots, both to save significantly staff and timing resources and avoid difficulties due to biomaterial transportation and storage. Molecular and genetic methods allowed to reveal new mutations and mutations common for Russian patients, also they made possible to carry out genetic counseling in families with the use of prenatal and pre-implantation diagnostics that in turn allowed to carry to term and give birth to three healthy children in families with family history. The presented changes of tyrosine and succinylacetone concentrations in blood of the examined patients before and during treatment showed modern options of the personified pathogenetic treatment and nutritional management of the tyrosinemia type 1 patients

Thrombotic events seem to be one of the most common and severe complications having a direct impact on the course of the disease in patients with cardiomyopathy.There were examined 94 children with dilated cardiomyopathy (DCMP) phenotype [49 children with dilated cardiomyopathy (DCMP), including 45 patients with non-compaction cardiomyopathy (NCMP) and remodeling in dilated phenotype]. Thromboses were diagnosed in 9 patients, including 7 DCMP and 2 NCMP cases. In 4 DCMP children, the thrombus was localized in the cavity of the left ventricle, one in the left atrium, the right ventricle, and the inferior vena cava. In NCMP children, intracardiac thrombus formation was not determined, one patient was diagnosed with an acute ischemic disorder of the cerebral circulation; in the second one, the thrombus was detected in the superior vena cava. Thrombosis in DCMP patients was detected against a background of a severe systolic dysfunction of the left ventricle (LVEF of below 30%), and in NCMP children with a moderate dysfunction. Also, the greatest prevalence rate of thrombotic complications was noted in Functional Class III and IV heart failure cases. At the same time, there was no established any influence of polymorphic markers G1691A of gene F5, G20210A of gene F2, C677T of MTHFR gene on the prevalence of thrombotic events. The authors believe the formation of thrombi with the severe LV dysfunction in children with cMYP should be taken into account in the determination the tactics of the treatment of such patients, as it is necessary to make a decision about administering antithrombotic therapy.

Aim: To evaluate the prevalence and clinical features of Fabry disease in patients with end-stage renal disease (ESRD) undergoing chronic hemodialysis. Methods: α-Galactosidase A activity was measured in the dried blood spots by tandem mass spectrometry in 5,572 dialysis patients (63.7% males). Diagnosis of Fabry disease was confirmed by sequencing of the GLA gene and by evaluating the globotriaosylsphingosine level in the dried blood spots. Results: Fabry disease was diagnosed in 20 (0.36%) patients at the median age of 43 years (28; 58). There were 19 males and 1 female. The prevalence of Fabry disease in dialysis patients was 0.53% in males and 0.05% in females. However, it was higher in males aged 30–49 years. Seventeen different GLA mutations were identified; 5 of them were novel. The median age at the initiation of hemodialysis was similar between patients with missense and nonsense mutations. Sixteen patients (80.0%) presented with typical symptoms of Fabry disease from childhood (neuropathic pain in 16, angiokeratoma in 7 and hypohidrosis/anhidrosis in 16). All patients had left ventricular hypertrophy, and 8 patients (40%) had a history of ischemic stroke. Two patients died (recurrent stroke in one and sudden cardiac death in another patient). Conclusions: Screening in at-risk patients remains the feasible approach to diagnose Fabry disease in patients with ESRD and their family members, given a low awareness of Fabry disease among the Russian nephrologists.

The recessive form of dystrophic epidermolysis bullosa (RDEB) is a debilitating disease caused by impairments in the junctions of the dermis and the basement membrane of the epidermis. Mutations in the COL7A1 gene induce multiple abnormalities, including chronic inflammation and profibrotic changes in the skin. However, the correlations between the specific mutations in COL7A1 and their phenotypic output remain largely unexplored. The mutations in the COL7A1 gene, described here, were found in the DEB register. Among them, two homozygous mutations and two cases of compound heterozygous mutations were identified. We created the panel of primary patient-specific RDEB fibroblast lines (FEB) and compared it with control fibroblasts from healthy donors (FHC). The set of morphological features and the contraction capacity of the cells distinguished FEB from FHC. We also report the relationships between the mutations and several phenotypic traits of the FEB. Based on the analysis of the available RNA-seq data of RDEB fibroblasts, we performed an RT-qPCR gene expression analysis of our cell lines, confirming the differential status of multiple genes while uncovering the new ones. We anticipate that our panels of cell lines will be useful not only for studying RDEB signatures but also for investigating the overall mechanisms involved in disease progression.

The article considers the solution of the actual problem connected with the integration of heterogeneous equipment (PLCs, drives, etc.) with a single CNC system. It formulates basic requirements for the connection mechanism of third-party equipment. It proposes the implementation of its own universal communication protocol with various devices, as well as the creation of a software component – of an external device controller which translates commands of the universal protocol into the commands of the protocol of the external device. The basic principles are considered, and the state machine of the communication protocol is built, the format of data exchange packets is determined. Thus, it is possible to connect devices of different manufacturers working on their own protocols to the CNC system. Two variants of interaction with third-party devices are discussed. The first is the implementation of a universal protocol by a programmable logic controller (PLC) or drive, and the second based on intermediate software module that interacts with third-party devices.

In 1917 Smolensk province stood on the second place by the quantity of sophomores of the Moscow university next to Vladimir province (139 and 158 students correspondingly). 7 districts out from 11 were represented. Mainly graduators of gymnasia and the Seminary entered the university. For the first time 8 girls became students. Principally the social structure of students included petty bourgeoisie, clergy and peasantry. Most part of students entered physics and mathematics department, much smaller part entered medical department and ones of law and of linguistics and history.

The article describes an approach to the development of logical control systems for small-scale sawmills, which allows automating algorithm creation and programming of control devices using the so-called SWITCH technology. The proposed approach allowed to develop a model of automatic control of KARA Master circular saw feed mechanism.

The paper deals with the conditions, methods, and support facilities for aircraft certification tests. Given as an example is determination of aerodynamic errors in altitude and speed measurements taken onboard Il-78M-90A aircraft.

Determine if early CT evaluation is justified in patients operated on for benign brain tumors.Researchers have recently questioned the common practice of referring all patients after cranial surgery for CT scans to rule out silent complications.The cohort included 257 consecutive patients who underwent surgical removal of a benign brain tumor in the years 2011-2016. The neuroradiology scans performed before and after surgery were reviewed. The postoperative findings considered significant were hemorrhage in ≥50% of the tumor bed, ischemic changes, worsening brain edema, and mass effect. The relationship of the CT findings with the neurological outcome and their effect on the clinical management were evaluated.No significant complications were found by CT in 247 patients (96%). In the remaining 10 patients (4%), CT showed increased brain edema in 5 and hemorrhage in 5. The clinical management was influenced by the CT findings in 6/10 patients. One had a temporary neurological deficit. None died or required a second operation.Elective patients operated on uneventfully for benign brain tumors rarely benefit from routine CT after surgery. In most cases, CT follow-up can be replaced by careful neurological monitoring. Exceptions to this rule may be based on clinical judgment and local resources.

Primary vesicoureteral reflux (VUR) is known to be the most common urological anomaly in children, witch affects 1-2% of pediatric population and 30-40% of children, developing urinary tract infections (UTIs). The hereditary and familial nature of VUR is well established and in several studies was proved that siblings of children with VUR have a higher incidence of reflux than it is in general pediatric population. Familial clustering of VUR implies that genetic factors have an important role in its pathogenesis, but to date no single major locus or gene for VUR has been identified and most researchers acknowledge that VUR is genetically heterogeneous. Improvements in genome wide scan techniques and continuously increasing knowledge of the genetic basis of VUR should lead us to further insights on VUR pathogenesis.

We propose mathematical models of errors of the onboard measurements of static pressure of an aircraft in the sliding modes of flight based on the use of hydrodynamic models of flow around thin bodies. We also analyze and estimate the schemes of location of Pitot static probes traditionally used in the aviation practice, as well as the algorithms intended for the compensation of errors in the calculators of air-data systems. The results of determination of the component of aerodynamic error in the sliding modes of flight are presented. The accumulated data have been obtained in the course of flight tests of numerous transport aircrafts.

Background. Cystic fibrosis is a hereditary disease that occurs as a result of mutations in the regulator gene of chloride ion transmembrane transport (CFTR). Finding mutations in the CFTR gene is necessary for identification of the clinical features of cystic fibrosis. Objective. Our aim was to identify genotype-phenotype correlations between mutations of the first class of pathogenicity and clinical manifestations of cystic fibrosis based on studying the prevalence and structure of CFTR gene mutations. Methods. The study included children under 18 years with cystic fibrosis admitted to hospital between 2013 and 2017. Biallelic mutations in the CFTR gene were the noninclusion criterion. The CFTR gene variants were analyzed by next-generation sequencing method. Results. In 125 patients with cystic fibrosis, 59 different variants of the CFTR gene were detected, 11 of them not previously described. The most common was the deletion c.1521_1523del found in 98 (39.2%) of the 250 analyzed CFTR gene alleles and the deletion c.1545_1546del found in 22/250 (8.8%) alleles. It has been shown that the mutation c.1545_1546del, p.Y515* was more often found in children of the Chechen nation — odds ratio (OR) 139 (95% confidence interval 15–1,257). It has been established that meconium ileus, pancreatic deficiency and cirrhosis are more common in patients with mutations of the first category of pathogenicity: OR 3.9 (95% CI 1.0–15.0), 4.4 (95% CI 1.8–11.1), and 351 (95% CI 17.5–7,046), respectively. The association of CFTR gene mutations with the development of bronchiectases and polypous pancinusitis has not been found. Conclusion . Correlations between the genotype and clinical manifestations of cystic fibrosis in Russian children with CFTR gene mutations of the first class of pathogenicity have been established.