Sports complex TRP as a motivational factor for active physical exercises for young students

The issue of preserving the health of students today is very serious. In this regard, it is important to create positive motivation in youth sports, development and improvement of physical qualities. Thus, the question arises, how to introduce students to physical education and sport through engaging them in the delivery of standards "TRP"Вопрос сохранения здоровья учащейся молодежи на сегодняшний день стоит очень остро. В связи с этим, важно создать положительную мотивацию у молодежи для занятий спортом, развития и совершенствования физических качеств. Таким образом, возникает вопрос, каким образом можно приобщить студентов к физкультуре и спорту через привлечение их к сдаче норм «ГТО

Atomic Mechanisms of Timothy Syndrome-Associated Mutations in Calcium Channel Cav1.2

Timothy syndrome (TS) is a very rare multisystem disorder almost exclusively associated with mutations G402S and G406R in helix IS6 of Cav1.2. Recently, mutations R518C/H in helix IIS0 of the voltage sensing domain II (VSD-II) were described as a cause of cardiac-only TS. The three mutations are known to decelerate voltage-dependent inactivation (VDI). Here, we report a case of cardiac-only TS caused by mutation R518C. To explore possible impact of the three mutations on interdomain contacts, we modeled channel Cav1.2 using as templates Class Ia and Class II cryo-EM structures of presumably inactivated channel Cav1.1. In both models, R518 and several other residues in VSD-II donated H-bonds to the IS6-linked α1-interaction domain (AID). We further employed steered Monte Carlo energy minimizations to move helices S4–S5, S5, and S6 from the inactivated-state positions to those seen in the X-ray structures of the open and closed NavAb channel. In the open-state models, positions of AID and VSD-II were similar to those in Cav1.1. In the closed-state models, AID moved along the β subunit (Cavβ) toward the pore axis and shifted AID-bound VSD-II. In all the models R518 retained strong contacts with AID. Our calculations suggest that conformational changes in VSD-II upon its deactivation would shift AID along Cavβ toward the pore axis. The AID-linked IS6 would bend at flexible G402 and G406, facilitating the activation gate closure. Mutations R518C/H weakened the IIS0-AID contacts and would retard the AID shift. Mutations G406R and G402S stabilized the open state and would resist the pore closure. Several Cav1.2 mutations associated with long QT syndromes are consistent with this proposition. Our results provide a mechanistic rationale for the VDI deceleration caused by TS-associated mutations and suggest targets for further studies of calcium channelopathies

The problem of the responsibility in the modern theory of morality

In this paper analyses the current status of research on the issue of responsibility, the attention is drawn to the change in the interpretation of responsibility and expanding her horizon, changing the vector responsibility and on the emergence of ethics of responsibility as a special trends in the modern theory of morality.В данной работе анализируется современное состояние исследований по проблеме ответственности, обращается внимание на изменения в трактовке ответственности, на расширение ее горизонта, смену вектора ответственности, появление этики ответственности как особого направления в современной теории морали

Ассоциации полиморфных вариантов rs2305619 и rs3816527 гена пентраксина-3 (PTX3) с особенностями клинического течения и исходов у пациентов с гипертрофической кардиомиопатией: результаты 11-летнего наблюдения.

The objective of this study was to determine the association of polymorphic variants rs2305619 and rs3816527 of the PTX3 gene with clinical profile and outcomes in hypertrophic cardiomyopathy (HCM) patients.Methods and materials. The study population consisted of 153 patients ≥18 years old with a confirmed diagnosis of HCM. The control group included 200 healthy donors. Duration of follow-up was 11 years (2008–2019 yrs.). The study design included a new model for determining variants of the clinical profile and outcomes of HCM. Polymorphic variants rs2305619 and rs3816527 of the PTX3 gene were genotyped by polymerase chain reaction.Results. The mortality rate in patients ≥18 years old with 1, 2 and 3 adverse pathways of HCM progression was significantly higher, compared with those without adverse pathways (р<0.001). A combination of chronic heart failure (CHF) with midrange and reduced LVEF (<49 %) with 1, 2 and 3 adverse pathways in HCM patients occurred more frequently, compared with those who had CHF with preserved LVEF (≥50 %) (odds ratio (OR) = 0.168, 95 % confidence interval (CI) =0.068–0.412, р<0.001). The genetic testing showed no significant differences in genotype and allele frequencies of polymorphic variants rs2305619 and rs3816527 of the PTX3 gene in patients with HCM and control groups. It was found a tendency for increase in GG genotype frequency (p<0.068) and significant increase in G allele frequency of rs2305619 of the PTX3 gene in HCM patients ≥18 years old and CHF with mid-range and reduced LVEF (<49 %) (A:G, OR=0.521, 95 % CI=0.301–0.902, p<0.019). HCM patients (age – 63 [58; 75] years) and type 2 diabetes mellitus demonstrated high prevalence in AG and GG genotypes (p<0.008) and G allele frequencies of rs2305619 of the PTX3 gene (A:G, OR =1.952, 95 % CI=1.076–3.542, p<0.026).Conclusions. HCM progression along 1 and more adverse pathways in patients ≥18 years old has been characterized with adverse outcome. G allele of rs2305619 of the PTX3 gene is associated with CHF with mid-range and reduced LVEF (<49 %) in HCM patients ≥18 years old. The associations of G allele and AG and GG genotypes of rs2305619 of the PTX3 gene with diabetes type 2 are observed in elderly HCM patients.Цель – изучить ассоциации полиморфных вариантов rs2305619 и rs3816527 гена пентраксина-3 (PTX3) с особенностями клинического течения и исходов у пациентов с гипертрофической кардиомиопатией (ГКМП).Методы и материалы. В исследование (2008–2019) включены 153 пациента в возрасте ≥18 лет с подтвержденным диагнозом ГКМП. Группу контроля составили 200 практически здоровых человек. Дизайн исследования включал в себя новую модель определения вариантов клинического течения и исходов ГКМП. Полиморфные варианты rs2305619 и rs3816527 гена PTX3 были идентифицированы методом полимеразной цепной реакции.Результаты. У пациентов с ГКМП в возрасте ≥18 лет при наличии одного, двух и трех путей прогрессирования заболевания смертность за 11 лет значимо превышала аналогичный показатель у пациентов с малосимптомным течением (р<0,001). Хроническая сердечная недостаточность (ХСН) со средней и сниженной фракцией выброса левого желудочка (ФВ ЛЖ) (<49 %) значимо чаще сочеталась с наличием одного, двух и трех путей прогрессирования заболевания, по сравнению с ХСН с сохраненной ФВ ЛЖ (≥50 %) (ОШ=0,168, 95 % ДИ=0,068–0,412, р<0,001). Значимых различий в распределении генотипов и аллелей полиморфных вариантов rs2305619 и rs3816527 гена PTX3 у больных ГКМП и контрольной группе получено не было. Аллель G rs2305619 гена PTX3 определялся достоверно чаще у пациентов с ГКМП и ХСН со средней и сниженной ФВ ЛЖ (<49 %), по сравнению с сохраненной ФВ ЛЖ (≥50 %) (A:G, ОШ=0,521, 95 % ДИ=0,301–0,902, p<0,019). Была определена тенденция к преобладанию генотипа GG rs2305619 гена PTX3 при наличии ХСН со средней и сниженной ФВ ЛЖ (<49 %) (p<0,068). У пациентов с ГКМП и сахарным диабетом (СД) II типа (возраст – 63 [58; 75] года) статистически значимо преобладали генотипы AG и GG (p<0,008) и аллель G rs2305619 гена PTX3 (A:G, ОШ =1,952, 95 % ДИ=1,076–3,542, p<0,026)

Systematic dissection of biases in whole-exome and whole-genome sequencing reveals major determinants of coding sequence coverage

Advantages and diagnostic effectiveness of the two most widely used resequencing approaches, whole exome (WES) and whole genome (WGS) sequencing, are often debated. WES dominated large-scale resequencing projects because of lower cost and easier data storage and processing. Rapid development of 3(rd) generation sequencing methods and novel exome sequencing kits predicate the need for a robust statistical framework allowing informative and easy performance comparison of the emerging methods. In our study we developed a set of statistical tools to systematically assess coverage of coding regions provided by several modern WES platforms, as well as PCR-free WGS. We identified a substantial problem in most previously published comparisons which did not account for mappability limitations of short reads. Using regression analysis and simple machine learning, as well as several novel metrics of coverage evenness, we analyzed the contribution from the major determinants of CDS coverage. Contrary to a common view, most of the observed bias in modern WES stems from mappability limitations of short reads and exome probe design rather than sequence composition. We also identified the similar to 500kb region of human exome that could not be effectively characterized using short read technology and should receive special attention during variant analysis. Using our novel metrics of sequencing coverage, we identified main determinants of WES and WGS performance. Overall, our study points out avenues for improvement of enrichment-based methods and development of novel approaches that would maximize variant discovery at optimal cost

2020 Clinical practice guidelines for Hypertrophic cardiomyopathy

Russian Society of Cardiology (RSC)With the participation: Russian Association of Cardiovascular SurgeonsEndorsed by: Research and Practical Council of the Ministry of Health of the Russian Federation Task Force: Gabrusenko S.A. (Chairman), Gudkova A.Ya.* (Chairman), Koziolova N.A. (Chairman), Alexandrova S.A., Berseneva M.I., Gordeev M.L., Dzemeshkevich S.L., Zaklyazminskaya E.V., Irtyuga O.B., Kaplunova V.Yu., Kostareva A.A., Krutikov A.N., Malenkov D.A., Novikova T.N., Saidova M.A., Sanakoev M.K., Stukalova O.V

Comparison of the risks of recurrent bleeding from class FI peptic ulcers after topical epinefrine topicle

The purpose of the study is to conduct a systematic review and meta-analysis of current data on the likelihood of relapses after the use of local injections of epinephrine for endoscopic hemorrhage control classes FI according to J.A. Forrest in the upper gastrointestinal tract. An additional goal of this study is to develop a method for extracting relevant information from open literary sources to fill the database of the AI Forrest decision support system.Цель исследования – провести систематический обзор и мета-анализ современных данных о вероятности рецидивов после применения местных инъекций эпинефрина для эндоскопической остановки кровотечения классов FI по J.А. Forrest в верхних отделах желудочно-кишечного тракта. Дополнительной целью данного исследования является отработка метода извлечения из открытых литературных источников актуальной информации для наполнения базы данных системы поддержки принятия решения «AI Forrest» врачом-эндоскопистом