[The suicides in the Russian Federation: review of national studies].

The epidemiological data of suicide rate, protective and risk factors is required to evaluate suicide losses, to develop appropriate interventions and to determine their effectiveness. Despite stable decreasing trend in suicide rates over the past three decades, the burden of suicides is determined by loss of young working-age population. In the post-Soviet Russia, fluctuations in suicide mortality indicators are associated with complicated periods of social economic transformations and radical changes of public policy. The risk factors also include economically depressive territories of residence, unemployment, psychoactive substance abuse, childhood and adolescence, family ill-being, incarceration, particular professional groups, physical illnesses, etc. The review established researchers' aspirations for topics improving understanding of suicide risk factors in population of Russia and needs of vulnerable groups. Such works are to result in better strategies of suicide prevention and development of new crisis care technologies. They identify problems in program implementation and provide important stimulus for determining global priorities in research and development areas.

The gender and age differences of persons with suicidal behavior.

The study examines cohort of people with suicidal behavior in the light of gender and age differences. The archive materials of the Kaluga Regional Psychiatric Hospital for the period of 2017-2018 were studied. The allocated 435 cases of hospitalizations with suicidal behavior are allocated to admissions with suicidal ideation and hospitalizations with suicidal attempt and self-harm with specified suicidal intentions. The data obtained was processed using the Microsoft Excel software applying the Yule's coefficient of association and Pearson's contingency coefficient, Pearson's χ2 test and Student's t-test. The results of study established no differences in suicidal manifestations adjusted for gender, but allow to distinguish risk age intervals. Thus, mean age in the group of admission with suicidal ideation was in the range of 29.8-35.2 years and 36.0-41.4 years in the group of suicidal attempt. In the age cohort of 5-19 years, probability of admission with suicidal ideation was higher than with suicidal attempt and self-harm. On the contrary, in the age range of 25-44 years, admission with suicidal attempt and self-harm prevailed. This information complements scientific evidence and points out directions for further research concerning prevention of mortality from external causes (suicide) in this area of public health theory.

[The detection of medication sensitivity of M.tuberculosis isolated from patients with tuberculosis with multiple medication resistance in testsystem "Sensititre MycoTB".]

The test-system "Sensititre MycoTB" was applied to analyze 159 cultures of M.tuberculosis isolated from patients with tuberculosis. According data of investigation in "Bactec 960" they are identified as cultures with multiple medicinal sensitivity. The detailed analysis of results of application of mentioned test-system (mycoTB) demonstrated that significant part of cultures with multiple medicinal sensitivity is sensitive to anti-tuberculosis pharmaceuticals. The significant part of cultures is characterized by "intermediate" sensitivity/resistance than can be established by mentioned test-system. This data permits enlarging possibilities of chemotherapy of tuberculosis.

[DETERMINATION OF CRITICAL CONCENTRATION OF CHEMOTHERAPY DRUGS FOR MYCOBACTERIUM TUBERCULOSIS SENSITIVITY EVALUATION USING Sensititre MyCoTB TEST SYSTEM].

AIM: Determination of critical concentration for chemotherapy drugs, widely used for tuberculosis treatment, for use in Mycobacterium tuberculosis drug sensitivity results evaluation by Sensititre MycoTB test-system. MATERIALS AND METHODS: Minimal inhibiting concentration (MIC) of isoniazid, rifampicin, streptomycin, ethambutol, amikacin, kanamycin, ofloxacin and moxifloxacin against conditionally sensitive and conditionally resistant strains of tuberculosis mycobacteria (TBM), isolated from various diagnostic material, obtained from patients with various forms of lung tuberculosis being treated in MCSPCTC hospital and dispensaries for tuberculosis control of Moscow, were studied in Sensititre MycoTB test system. RESULTS: Critical concentration of chemotherapy drugs for MycoTB test system was determined as a result of the obtained MIC values analysis as the minimal concentration that suppressed growth of 95% of sensitive strains and does not obstruct growth of 95% of resistant. The following MIC values were established: streptomycin--1.0, isoniazid--0.25, rifampicin--1.0, ethambutol--4.0, ofloxacin--2.0, moxifloxacin--0.25, kanamycin--2.5 and amikacin- 1.0 µg/ml. CONCLUSION: The developed critical concentration of the mentioned preparations is currently used for evaluation of sensitivity/ resistance of TBM clinical isolates from MCSPCTC.

[Prognostic value of clinical and morphological characteristics in radiation and combined treatment for tongue cancer].

It is now possible to identify several key factors that determine biological characteristics of squamous cell cancer of the head and neck: genes p53, p16, cyclin D1, P13-K/Akt connected with metastasis proteins (proteases, proteins mesenchymal cells, cell adhesion molecules chemokines), angiogenesis factors (VEGF, PDGF, FGF, TGF-alpha and TGF-beta), IL-8; epidermal growth factor receptors. An important role of tumor cells plays microenvironment. Of course the above mentioned is only a small part of the factors that determine the livelihoods and the activity of cancer cells. All of these factors are potential predictors of the effectiveness of radiation and chemoradiation treatment and actively studied in recent decades.

Recurrent triploidy due to a failure to complete maternal meiosis II: whole-exome sequencing reveals candidate variants.

Triploidy is a relatively common cause of miscarriage; however, recurrent triploidy has rarely been reported. A healthy 34-year-old woman was ascertained because of 18 consecutive miscarriages with triploidy found in all 5 karyotyped losses. Molecular results in a sixth loss were also consistent with triploidy. Genotyping of markers near the centromere on multiple chromosomes suggested that all six triploid conceptuses occurred as a result of failure to complete meiosis II (MII). The proband's mother had also experienced recurrent miscarriage, with a total of 18 miscarriages. Based on the hypothesis that an inherited autosomal-dominant maternal predisposition would explain the phenotype, whole-exome sequencing of the proband and her parents was undertaken to identify potential candidate variants. After filtering for quality and rarity, potentially damaging variants shared between the proband and her mother were identified in 47 genes. Variants in genes coding for proteins implicated in oocyte maturation, oocyte activation or polar body extrusion were then prioritized. Eight of the most promising candidate variants were confirmed by Sanger sequencing. These included a novel change in the PLCD4 gene, and a rare variant in the OSBPL5 gene, which have been implicated in oocyte activation upon fertilization and completion of MII. Several variants in genes coding proteins playing a role in oocyte maturation and early embryonic development were also identified. The genes identified may be candidates for the study in other women experiencing recurrent triploidy or recurrent IVF failure.

Exome sequencing identifies mutations in KIF14 as a novel cause of an autosomal recessive lethal fetal ciliopathy phenotype.

Gene discovery using massively parallel sequencing has focused on phenotypes diagnosed postnatally such as well-characterized syndromes or intellectual disability, but is rarely reported for fetal disorders. We used family-based whole-exome sequencing in order to identify causal variants for a recurrent pattern of an undescribed lethal fetal congenital anomaly syndrome. The clinical signs included intrauterine growth restriction (IUGR), severe microcephaly, renal cystic dysplasia/agenesis and complex brain and genitourinary malformations. The phenotype was compatible with a ciliopathy, but not diagnostic of any known condition. We hypothesized biallelic disruption of a gene leading to a defect related to the primary cilium. We identified novel autosomal recessive truncating mutations in KIF14 that segregated with the phenotype. Mice with autosomal recessive mutations in the same gene have recently been shown to have a strikingly similar phenotype. Genotype-phenotype correlations indicate that the function of KIF14 in cell division and cytokinesis can be linked to a role in primary cilia, supported by previous cellular and model organism studies of proteins that interact with KIF14. We describe the first human phenotype, a novel lethal ciliary disorder, associated with biallelic inactivating mutations in KIF14. KIF14 may also be considered a candidate gene for allelic viable ciliary and/or microcephaly phenotypes.

[Comparing performance of "TB-BIOCHIP", "Xpert MTB/RIF" and "genotype MTBDRplus" assays for fast identification of mutations in the Mycobacterium tuberculosis complex in sputum from TB patients].

The frequency of mutations causing drug resistance in MTB isolates were studied in the respiratory material obtained from TB-patients in the Moscow Region. In izoniazid-resistant isolates, the most prevalent mutation was found to be the Ser315Thr substitution in the katG gene (15.8%) whereas the most frequent mutations in multidrug-resistant isolates were Ser531Leu and Ser315Thr in the rpoB and katG genes (26.3%), or a combination of these two substitutions with a T15 mutation in the inhA gene (5.3%). We compared performance of three molecular assays--"TB-BIOCHIP" ("BIOCHIP-IMB", Ltd, Russia), Xpert MTB/RIF ("Cepheid", USA) and GenoType MTBDRplus ("Hain Life-science", Germany), with the efficiency of luminescent microscopy, and phenotypic drug-suscepibility testing in an automated system BACTEC MGIT 960 (Becton, Disckinson and Company, USA). Xpert MTB/RIF, TB-BIOCHIP and GenoType MTBDRplus detected MTB in sputum in 92, 78 and 49% of all culture-positive cases, respectively. The agreement between standard cultural data and molecular DST results for Xpert MTB/RIF (resistance towards rifampicin), for TB-BIOCHIP and GenoType MTBDRplus (resistance towards rifampicin and izoniazid) amounted to 100, 97 and 100% respectively. Summing up, Xpert MTB/RIF was concluded to be the most efficient assay for primary detection of MTB, whereas the TB-BIOCHIP was shown to be the only molecular assay sensitive enough for simultaneous detection of MTB DNA and for revealing multidrug resistance in sputum (i.e. resistance to both first-line anti-TB drugs, rifampicin and izoniazid).

Determination of critical concentrations of moxifloxacin and gatifloxacin for drug susceptibility testing of Mycobacterium tuberculosis in the BACTEC MGIT 960 system.

OBJECTIVES: To determine critical concentrations of moxifloxacin and gatifloxacin for rapid evaluation of drug susceptibility of Mycobacterium tuberculosis in Middlebrook 7H9 broth using the automated system BACTEC™ MGIT™ 960. METHODS: In total we studied 152 strains. Critical concentrations of moxifloxacin and gatifloxacin in the BACTEC™ MGIT™ 960 and on Lowenstein-Jensen medium were determined using a panel of 68 strains. The proportion method on Middlebrook 7H10 medium was used as a reference method. Drug susceptibility testing against fluoroquinolones was done for the other 84 strains using the established critical concentrations. The gyrA and gyrB genes of all strains were studied by molecular tests. RESULTS: The critical concentrations determined for moxifloxacin and gatifloxacin were 0.25 mg/L in the BACTEC™ MGIT™ 960 system and 0.75 mg/L on Lowenstein-Jensen medium (absolute concentration method). CONCLUSIONS: The moxifloxacin and gatifloxacin critical concentrations that we have established are reliable for rapid drug susceptibility testing in the BACTEC™ MGIT™ 960.

[Polymorphism of the genes IL-1RA and TNF-alpha in patients with gastritis and duodenal ulcer associated with Helicobacter pylori].

The goal of this work was to determine the rate of the polymorphism of the genes-antagonists of receptor IL-1 (IL-1RA) and TNF-alpha in patients with gastritis and duodenal ulcer associated with Helicobacter pylori. The receptors were tested for the clinical manifestation of the disease. A total of 126 patients with different gastroduodenal pathology and H. pylori in autopsy were tested. The results of this work demonstrated a correlation between the risk of duodenal ulcer and allele A of gene TNF-alpha in position 308 in the patients. The analysis of the gene-IL-1RA polymorphism demonstrated statistically significant difference between the patients in the frequency of the genotype 2/l. The results of this work showed that parallel typing of the genes of H. pylori in virulence was required for characterization of the bacteria-patient association. The correlation between the results of the typing with polymorphism of genes of cytokines in patient autopsy was also required.

Detection of mutations in Mycobacterium tuberculosis genome determining resistance to fluoroquinolones by hybridization on biological microchips.

We developed a method of identification of Mycobacterium tuberculosis with simultaneous evaluation of the sensitivity to fluoroquinolones on a biological microchip array. The method of multiplex two-staged PCR followed by hybridization of a biochip makes it possible to detect 8 mutant variants of gyrA gene occurring in fluoroquinolone-resistant strains (approximately 85% all resistant forms) within 1 day. Using this method we analyzed 107 cultures isolated from patients with tuberculosis and 78 sputum samples. Mutations in gyrA gene were detected in 48 (92%) resistant strains. Natural S95T polymorphism in gyrA gene was detected in all resistant and in 76% sensitive strains. The sensitivity and specificity of the proposed method calculated on the basis of the analysis of sputum samples (n=78) were 94 and 100%, respectively.

[Use of molecular-biological microchip TB-BIOCHIP-2 for detecting of Mycobacterium tuberculosis with multidrug resistance to fluoroquinolones in patients with new detected and chronic tuberculosis].

At present the left-handed "respiratory" quinolones such as moxifloxacin and levofloxacin are the most promising drugs for therapy of multidrug resistant tuberculosis (MDR). Fast and specific diagnostics of sensitivity of M. tuberculosis (MBT) with MDR to this group of drugs is required for timely prescription of adequate chemotherapy and its correction in case of MBT resistance to fluoroquinolones. A new generation of biological microchips - TB-BIOCHIP-2 makes possible to detect 9 mutation types in quinolones resistant determination region (QRDR) of gene. About 800 samples from 169 patients in Antituberculosis center were studied. In patients with new detected tuberculosis 23.5% MBT resistant to isoniazid and rifampicin (MDR) and sensitive to fluoroquinolones were revealed. In patients with chronic tuberculosis 65.5% MBT-MDR were revealed. Our results were confirmed with detecting ofloxacin resistance on Lowenstein - Jensen. In addition efficiency of TB-BIOCHIP-2 to control drug testing sensitivity of MBT-MDR on fluoroquinolones was confirmed.

[Investigation of Mycobacterium tuberculosis sensitivity to fluoroquinolone, by revealing gyrA gene mutations].

The resistance of Mycobacterium tuberculosis (MBT) to fluoroquinolones is associated with the mutations concentrated in the gyrA gene that is a structural gene of a gyrase A subunit. Detection of mutations in this portion of the gene allows the sensitivity of MBT to this group of drugs to be rapidly determined.

[Potentialities of laboratory diagnosis in tuberculous meningitis].

The results of examination of 84 patients with tuberculosis of the central nervous system were used to make comparative clinical and laboratory studies. They revealed that lymphocytosis detected in the cerebrospinal fluid (CF), particularly the prevalence of lymphocytes (more than 50%), and decreased levels of chlorides in the cytogram were of value in the comprehensive diagnosis of tuberculous meningitis. The detection of CF Mycobacterium tuberculosis (MBT) (applying the whole currently available set of methods) is an absolute criterion for the diagnosis of tuberculous meningitis (however, with, unfortunately, few number positive results). The detection of mycobacterial DNA, antigens, and tuberculosis antibodies is an impotent component of a diagnostic complex for tuberculous meningitis. The determination of cytosis, protein, glucose, chlorides, lymphocytic subpopulations, soluble gamma-interferon mediators, mycobacteria, DNA, MBT antigens, and tuberculosis antibodies in SF is essential in treating tuberculous meningitis.

[The composition and drug sensitivity of a mycobacterial population in patients with suspected tuberculosis].

By using the diagnostic material (175 sputum samples and 103 bronchoalveolar lavage fluid samples) taken from 39 patients with suspected tuberculous infection during a 2.5-month follow-up, the authors traced the time course of changes in the composition and drug sensitivity of a mycobacterial population to rifampicin. Along with the traditional microbiological studies, the latest molecular biological studies, a TB-BIOCHIP test system (enzyme immunoassay) in particular, were employed to detect the bacterial and L-transformed forms of the causative agent. A molecular biological assay was first developed to detect the drug sensitivity of L-forms of Mycobacterium tuberculosis.

[The characteristics of the sensitivity of Mycobacterium tuberculosis to rifampicin and isoniazid through determination of mutations in the genes rpoB, katG, inhA, oxyR, and kasA by different molecular biological assays].

Two hundred and two patients with different forms of pulmonary tuberculosis were examined to study the characteristics of sensitivity with the signs of multidrug resistance to rifampicin and isoniazid, by using a microbiological assay of the absolute concentrations and determining mutations in the genes rpoB, katG, inhA, oxyR, and kasA, by employing different molecular biological assays. Mycobacterium tuberculosis (MBT) DNA was isolated from both a diagnostic material (such as sputum, bronchial secretion), and clinical MBT isolates. By showing a higher sensitivity and a higher specificity, as cultural techniques, molecular biological assays of MBT drug sensitivity in patients with tuberculosis were ascertained to accelerate its diagnosis until the patient was admitted to a clinic.

[New technologies in the determination of drug susceptibility in Mycobacterium tuberculosis]. / Novye tekhnologii opredeleniia lekarstvennoi chuvstvitel'nosti Mycobacterium tuberculosis.

A variety of mutations in the genes rpoB, katG, inhA, ahpC, kasA was studied by using different molecular biological methods (conformational polymorphism of single-chain fragments, heteroduplex analysis, biochips) in rifampicin- and isoniazid-resistant Mycobacterium tuberculosis (MBT) strains isolated from patients with pulmonary tuberculosis. Twenty-nine mutation combinations were identified in the MBT strains. The use of biochips is the most promising method for identifying the type of mutations responsible for the simultaneous resistance to rifampicin and isoniazid. Detection of several MBT strains in one patient requires the use a combination of molecular biological and microbiological studies.

Typing of Mycobacterium tuberculosis strains resistant to rifampicin and isoniazid by molecular biological methods.

Mutations in the rpoB, katG, inhA, oxyR/ahpC genes in rifampicin- and isoniazid-resistant M. tuberculosis strains isolated from residents of Moscow, Astrakhan', and Moldova Republic were studied by molecular biological methods (heteroduplex analysis, single strand conformational polymorphism, biochips). Twenty-five combinations of mutations were detected. Some differences in the type distribution of detected mutations were found. The use of biochips is the most perspective method for determining the type of mutation.

[Synthesis and tuberculostatic activity of fluoridized 3-Z-hydrazine-2-benzoyl acrylates and their cyclization products]. / Sintez i tuberkulostaticheskaia aktivnost' ftorirovannykh 3-Z-gidrazino-2-benzoilakrilatov i produktov ikh tsiklizatsii.

A rapid development of the resistance of drugs and their toxic and adverse reactions suggest that new antituberculous drugs should be designed. Of the greatest importance is isoniazid resistance. Testing new compounds (IIa, b) has established that the minimum inhibitory concentration of the drug (IIa), 0.39 microgram/ml suppresses the growth of Mycobacterium tuberculosis (MBT) in the macrophages up to 50%, that of the drug (IIb), 1.56 micrograms/ml, causes death in 25% of cases, which is indicative of the high activity of compounds (IIa, b) against MBT.