Role of genetic research in the prevention of life-threatening rhythm and cardiac conduction disorders in young people

According to epidemiological studies, in Russia there is a tendency towards an increase in sudden cardiac death (SCD), including among young workingage people. The leading mechanism for SCD in young patients, including those with undifferentiated connective tissue disease, is recognized as rhythm and conduction disorders. At the same time, the most tragic cases are the first and only manifestation of SCD in children and young people without structural heart disease. The article presents a brief analysis of the genetic causes of life-threatening rhythm and conduction disorders in young people, as well as a generalization of the modern possibilities of a personalized diagnostic approach from the standpoint of early cardiovascular prevention. Timely genetic diagnosis of SCD risk makes it possible to identify a predisposition to the development of a fatal event long before its occurrence, which contributes to the timely implementation of preventive measures within a high cardiovascular risk strategy and secondary prevention, maintaining working capacity, creative and social activity of young patients, and improving the quality of life

Дисплазия соединительной ткани: пульмонологические аспект

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Practical efficacy and safety of Konsilar D24 in patients with hypertension: data from the KONSONANS program

Aim. In practice, to evaluate the efficacy, safety and long-term adherence to therapy with a fixed-dose combination of ramipril/indapamide (Konsilar-D24) in patients with grade 1-2 hypertension (HTN) who have not achieved blood pressure (BP) control with prior therapy or have not taken antihypertensive therapy.Material and methods. This multicenter open-label observational program included 524 patients with grade 1-2 HTN who did not take antihypertensive therapy or did not reach the target BP level with mono or dual antihypertensive therapy, as well as patients shifted to Konsilar-D24 therapy no later than two weeks before the start of the program. All patients signed a written informed consent to participate in the program. The safety analysis set includes all patients who have taken at least one dose of a fixed-dose combination of ramipril/indapamide and have visited physician at least once during the program. The effectiveness analysis set included all patients in the safety population who completed the study in accordance with protocol (n=511). Clinical systolic blood pressure (SBP), diastolic BP (DBP) and heart rate were assessed at baseline, as well as at 0,5, 1, 3 and 6 months of treatment. A post hoc subgroup analysis of changes in BP and heart rate was performed depending on age, sex and baseline body mass index.Results. The fixed-dose combination of ramipril with indapamide significantly reduced SBP and DBP after 2-week treatment (-20,9±10,1 mm Hg; pConclusion. Despite the limitations inherent in observational studies, the KONSONANS program has demonstrated high efficacy and safety of fixed-dose combination of ramipril/indapamide taken once a day in hypertensive patients. Ramipril/indapamide fixed-dose combination therapy significantly improved BP control and achieved even lower individual target BP levels in the majority of hypertensive patients

Повторные пневмонии у детей с дисплазией соединительной ткани: ретроспективное клинико-морфологическое исследование

An analysis of medical documents and morphological examination of resected lung samples was done in 25 children had been operated for repeated pneumonias. All the children (100 %) were diagnosed undifferentiated connective tissue dysplasia (CTD) with marked clinical features. Morphological substrate of the repeated pneumonias was various defects of the lung growth. The results showed that the CTD as a genetic systemic pathology provided repeated pneumonias in structural abnormalities of the lungs. This fact should be taken into account in the diagnostic work-up.Проведен анализ медицинской документации и результатов морфологического исследования резецированных участков легких у 25 детей, оперированных по поводу повторных пневмоний. У 100% детей во время осмотра диагностирована недифференцированная дисплазия соединительной ткани (ДСТ) с выраженными клиническими проявлениями. Морфологическим субстратом повторных пневмоний явились различные варианты порочного развития легких. Результаты исследования свидетельствуют, что ДСТ как генетически детерминированный системный процесс предрасполагает к возникновению повторных пневмоний на фоне структурных аномалий легких, что необходимо учитывать в диагностическом процессе

Спонтанный пневмоторакс и дисплазия соединительной ткани: молекулярно-генетические исследования

Summary. To evaluate a role of polymorphic variants of alpha1-antitrypsin (AAT) genes and matrix metalloproteinase (MMP) genes for heritable susceptibility to bullous emphysema and primary spontaneous pneumothorax (PSP) in patients with connective tissue dysplasia (CTD), we analyzed polymorphic loci of PIZ (Glu342Lys), PIS (Glu264Val), MMP1 (1607insG), MMP9 (C-1562T), MMP12 (A-82G), and TIMP1 (С536Т) genes and studied serum AAT concentration. We did not find any significant difference between prevalence of the Z- and S-mutations of PI gene and serum AAT concentration between groups. MMP1 homozygous GG/GG genotype was associated with risk of PSP development (odds ratio (OR), 2.23; 95 % confidence interval (СI): 1.34–3.73), MMP1 GG allele (OR, 2.27; 95 % CI: 1.61–3.20), MMP9 heterozigous С/Т genotype (OR, 2.43; 95%CI: 1.37–4.31), MMP9 homozygous Т/Т genotype (OR, 4.38; 95 % CI: 1.12–20.00), MMP9 T allele (OR, 2.78; 95 % CI: 1.74–4.46). All alleles and genotypes were found significantly more often in patients with signs of CTD. No statistically significant difference for any polymorphic locus of the studied genes was seen between prevalence of allele variants in patients with PSP but not having CTD and in population sample.Резюме. С целью оценки роли полиморфных вариантов генов альфа1-антитрипсина (α1-АТ) и матриксных металлопротеиназ (MMP) в формировании буллезной эмфиземы и первичного спонтанного пневмоторакса (СП) у пациентов с дисплазией соединительной ткани (ДСТ) проведен анализ полиморфных локусов PIZ (Glu342Lys), PIS (Glu264Val), MMP1 (1607insG), MMP9 (C-1562T), MMP12 (A-82G), TIMP1 (С536Т) и количественное определение α1-АТ в сыворотке крови нефелометрическим методом. Значимых различий частоты Z- и S-мутаций гена PI и концентрации α1-АТ в сыворотке крови между группами не выявлено. Ассоциации с риском развития первичного СП выявлены для гомозиготного генотипа GG / GG гена MMP1 (отношение риска (OР) – 2,23, 95%-ный доверительный интервал (ДИ) – 1,34–3,73), аллеля GG гена MMP1 (OР – 2,27, 95%-ный ДИ – 1,61–3,20), гетерозиготного генотипа С / Т гена MMP9 (OР – 2,43, 95%-ный ДИ – 1,37–4,31), гомозиготного генотипа Т / Т гена MMP9 (OР – 4,38, 95%-ный ДИ – 1,12–20,00), аллеля Т гена MMP9 (OР – 2,78, 95%-ный ДИ – 1,74–4,46). Все вышеперечисленные аллели и генотипы достоверно чаще встречались у пациентов с признаками ДСТ. Статистически значимых различий между частотой аллельных вариантов у пациентов с первичным СП, не имеющих признаков ДСТ, и популяционной выборкой не было получено ни для одного полиморфного локуса изучаемых генов

Single hadron response measurement and calorimeter jet energy scale uncertainty with the ATLAS detector at the LHC

The uncertainty on the calorimeter energy response to jets of particles is derived for the ATLAS experiment at the Large Hadron Collider (LHC). First, the calorimeter response to single isolated charged hadrons is measured and compared to the Monte Carlo simulation using proton-proton collisions at centre-of-mass energies of sqrt(s) = 900 GeV and 7 TeV collected during 2009 and 2010. Then, using the decay of K_s and Lambda particles, the calorimeter response to specific types of particles (positively and negatively charged pions, protons, and anti-protons) is measured and compared to the Monte Carlo predictions. Finally, the jet energy scale uncertainty is determined by propagating the response uncertainty for single charged and neutral particles to jets. The response uncertainty is 2-5% for central isolated hadrons and 1-3% for the final calorimeter jet energy scale.Comment: 24 pages plus author list (36 pages total), 23 figures, 1 table, submitted to European Physical Journal