Lack of association between genetic markers on chromosome 16q22-Q24 and type 1 diabetes in Russian affected families

Aim To evaluate whether the T1D susceptibility locus on chromosome 16q contributes to the genetic susceptibility to T1D in Russian patients. Method Thirteen microsatellite markers, spanning a 47-centimorgan genomic region on 16q22-q24 were evaluated for linkage to T1D in 98 Russian multiplex families. Multipoint logarithm of odds (LOD) ratio (MLS) and nonparametric LOD (NPL) values were computed for each marker, using GENEHUNTER 2.1 software. Four microsatellites (D16S422, D16S504, D16S3037, and D16S3098) and 6 biallelic markers in 2 positional candidate genes, ICSBP1 and NQO1, were additionally tested for association with T1D in 114 simplex families, using transmission disequilibrium test (TDT). Results A peak of linkage (MLS = 1.35, NPL = 0.91) was shown for marker D16S750, but this was not significant (P = 0.18). The subsequent linkage analysis in the subset of 46 multiplex families carrying a common risk HLA-DR4 haplotype increased peak MLS and NPL values to 1.77 and 1.22, respectively, but showed no significant linkage (P = 0.11) to T1D in the 16q22-q24 genomic region. TDT analysis failed to find significant association between these markers and disease, even after the conditioning for the predisposing HLA-DR4 haplotype. Conclusion Our results did not support the evidence for the susceptibility locus to T1D on chromosome 16q22-24 in the Russian family data set. The lack of association could reflect genetic heterogeneity of type 1 diabetes in diverse ethnic groups

GENETIC POLYMORPHISM OF INFLAMMATORY FACTORS IS ASSOCIATED WITH THROMBOEMBOLIC COMPLICATIONS OF ATRIAL FIBRILLATION

Aim. To reveal the association of hereditary specifics of inflammatory factors with the adverse risk in atrial fibrillation (AF).Material and methods. Totally 258 patients studied (68,5±0,67 y. o.) with nonvalvular AF, recording the events as ischemic stroke, myocardial infarction, venous and arterial thromboembolism. Mean follow-up was 455±11,71 days.Results. Factors that are independently associated with ischemic stroke development in patients not receiving anticoagulants (n=101), were the allele C of polymorphic marker rs2228145(А/С) of gene IL-6 receptor (OR 13,25 CI 1,57112,18, р=0,018), age ?75 y. o. (OR 1,1, CI 1,008-1,2, р=0,032) and EF LV (OR 0,97 CI 0,94-0,99 р=0,027), with a “thrombotic endpoint” development — DM (OR 4,3 CI 1,46-12,45 р=0,008), EF LV (OR 0,96 CI 0,94-0,98, р<0,0001) and carriage of allele C of polymorphic marker rs2228145(А/С) of receptor to IL-6 gene (OR 4,03 CI 1,0715,26, р=0,04). There was no association with adverse outcomes in genes IL-6 polymorphisms as (G(-174)C and G(-572)C), ИЛ-10 (C(-819)T), ФНО (G(-238)A, G(-308)A and ФНО? rs180630). In those receiving adequate anticoagulant therapy (n=157) there was no significant association of IL-6 receptor gene polymorphism with adverse outcomes.Conclusion. Therefore, the carriage of allele C of polymorphic marker rs2228145(А/С) of the IL-6 receptor gene might be an independent risk marker for adverse outcome in non-valvular AF, potentially, being a selection tool for those patients not having enough high risk according to common scores

Competing ideologies of Russia's civil society

Many analysts and public opinion makers in the West conflate the notions of Russia’s non-systemic liberal opposition and the country’s civil society. Indeed, despite garnering the support of a minority of Russia’s population, non-systemic liberal opposition represents a well-organized civic group with a clearly articulated agenda and the ability to take action. Yet, does Russia’s civil society end there? A closer look at the country’s politics shows that Russia has a substantial conservative-traditionalist faction that has also developed agenda for action and formulated opinions. This group is anti-liberal rather than illiberal ideologically and pro-strong state/pro a geopolitically independent Russia rather than pro-Kremlin politically. The interaction between liberal and conservative civic groups represents the battle of meanings, ideas, and ethics, and ultimately determines the future trajectory of Russia’s evolution. Thus, the analysis of Russia’s civil society must represent a rather more nuanced picture than a mere study of the liberal non-systemic opposition. This article will examine the complexity of Russia’s civil society scene with reference to the interplay between the liberal opposition and conservative majority factions. The paper will argue that such complexity stems from ideological value pluralism that falls far beyond the boundaries of the liberal consensus, often skewing our understanding of political practice in Russia

A structured telephone-delivered intervention to reduce problem alcohol use (Ready2Change): study protocol for a parallel group randomised controlled trial

Background: Current population surveys suggest around 20% of Australians meet diagnostic criteria for an alcohol use disorder. However, only a minority seek professional help due to individual and structural barriers, such as low health literacy, stigma, geography, service operating hours and wait lists. Telephone-delivered interventions are readily accessible and ideally placed to overcome these barriers. We will conduct a randomised controlled trial (RCT) to examine the efficacy of a standalone, structured telephone-delivered intervention to reduce alcohol consumption, problem severity and related psychological distress among individuals with problem alcohol use. Methods/design: This is a single site, parallel group, two-arm superiority RCT. We will recruit 344 participants from across Australia with problem alcohol use. After completing a baseline assessment, participants will be randomly allocated to receive either the Ready2Change (R2C) intervention (n = 172, four to six sessions of structured telephone-delivered intervention, R2C self-help resource, guidelines for alcohol consumption and stress management pamphlets) or the control condition (n = 172, four phone check-ins < 5 min, guidelines for alcohol consumption and stress management pamphlets). Telephone follow-up assessments will occur at 4-6 weeks, 3 months, 6 months and 12 months post-baseline. The primary outcome is the Alcohol Use Disorders Identification Test (AUDIT) score administered at 3 months post-baseline. Secondary outcomes include change in AUDIT score (6 and 12 months post-baseline), change in number of past-month heavy drinking days, psychological distress, health and wellbeing, quality of life, client treatment evaluation and cost effectiveness. Discussion: This study will be one of the first RCTs conducted internationally to examine the impact of a standalone, structured telephone-delivered intervention to address problem alcohol use and associated psychological morbidity. The proposed intervention is expected to contribute to the health and wellbeing of individuals who are otherwise unlikely to seek treatment through mainstream service models, to reduce the burden on specialist services and primary care providers and to provide an accessible and proportionate response, with resulting cost savings for the health system and broader community. Trial registration: Australian New Zealand Clinical Trials Registry, ACTRN12618000828224. Pre-registered on 16 May 2018

Primary and secondary structure of rat 28 S ribosomal RNA.

The primary structure of rat (Rattus norvegicus) 28 S rRNA is determined inferred from the sequence of cloned rDNA fragments. The rat 28 S rRNA contains 4802 nucleotides and has an estimated relative molecular mass (Mr, Na-salt) of 1.66 X 10(6). Several regions of high sequence homology with S. cerevisiae 25 S rRNA are present. These regions can be folded in characteristic base-paired structures homologous to those proposed for Saccharomyces and E. coli. The excess of about 1400 nucleotides in the rat 28 S rRNA (as compared to Saccharomyces 25 S rRNA) is accounted for mainly by the presence of eight distinct G+C-rich segments of different length inserted within the regions of high sequence homology. The G+C content of the four insertions, containing more than 200 nucleotides, is in the range of 78 to 85 percent. All G+C-rich segments appear to form strongly base-paired structures. The two largest G+C-rich segments (about 760 and 560 nucleotides, respectively) are located near the 5'-end and in the middle of the 28 S rRNA molecule. These two segments can be folded into long base-paired structures, corresponding to the ones observed previously by electron microscopy of partly denatured 28 S rRNA molecules

Mutatsiya S1167T v gene katalazy i razvitie neyropatii pri sakharnom diabete 1 tipa

Актуальность Диабетическая нейропатия (ДН) относится к поздним сосудистым осложнениям сахарного диабета (СД). Основным метаболическим нарушением является гипергликемия. Повышенные концентрации глюкозы вызывают резкое повышение содержания свободных кислородных радикалов и продуктов перекисного окисления липидов (ПОЛ) в крови, что приводит организм в состояние окислительного стресса. Каталаза является одним из основных ферментов системы антиоксидантной защиты, осуществляющим разложение перекиси водорода на воду и свобод-ный кислород. Цель работы Оценка вклада гена CAT в предрасположенность к ДН при СД 1 типа в московской популяции. Материалы и методы Анализировали геномную ДНК 128 больных СД 1 типа с наличием и отсутствием ней?ропатии. Полиморфный участок гена CAT амплифицировали с помощью полимеразной цепной реакции (ПЦР). Частоту встречаемости аллелей и генотипов гена CAT в груп?пах ДН+ и ДН- сравнивали с помощью точного критерия Фише?ра. Результаты. Наиболее распространенным вариантом среди генотипов были гомозиготы СС (62,2%), содержание которых в 7,7 раза превосходило встречаемость гомозигот по аллелю Т, гетерозиготность составила 29.7%. Полиморфный маркер С1167Т гена CAT ассоциирован с развитием нейропатии при СД 1 типа в московской популяции. Аллель С (RR=2,55) и генотип СС (RR=2,60) являются маркерами риска ДН, в то время как аллель Т (RR=0,39) и гомозиготы ТТ (RR=0,30), напротив, предохраняют от раннего развития ДН. Выводы Видимо, в популяции Москвы предрасполагающая роль генотипа СС выражена сильнее, чем предохраняющее действие гомозигот ТТ

POLYMORPHISM OF CHRONIC GLOMERULONEPHRITIS ASSOCIATION WITH ADPRT1 GENE VAL762ALA

Association of polymorphic ADPRT1 gene Val762Ala marker, encoding poly(ADP-ribose)polymerase-l, with the development, course and progress of chronic glomerulonephritis was revealed during investigation. The risk of the chronic glomerulonephritis development is higher in patients-carriers of Val-allele and Val/Val-genotype and lower in those with Ala-allele and Ala/Ala-genotype