Role of Pannexin 1 ATP-Permeable Channels in the Regulation of Signaling Pathways during Skeletal Muscle Unloading

Skeletal muscle unloading results in atrophy. We hypothesized that pannexin 1 ATP-permeable channel (PANX1) is involved in the response of muscle to unloading. We tested this hypothesis by blocking PANX1, which regulates efflux of ATP from the cytoplasm. Rats were divided into six groups (eight rats each): non-treated control for 1 and 3 days of the experiments (1C and 3C, respectively), 1 and 3 days of hindlimb suspension (HS) with placebo (1H and 3H, respectively), and 1 and 3 days of HS with PANX1 inhibitor probenecid (PRB; 1HP and 3HP, respectively). When compared with 3C group there was a significant increase in ATP in soleus muscle of 3H and 3HP groups (32 and 51%, respectively, p < 0.05). When compared with 3H group, 3HP group had: (1) lower mRNA expression of E3 ligases MuRF1 and MAFbx (by 50 and 38% respectively, p < 0.05) and MYOG (by 34%, p < 0.05); (2) higher phosphorylation of p70S6k and p90RSK (by 51 and 35% respectively, p < 0.05); (3) lower levels of phosphorylated eEF2 (by 157%, p < 0.05); (4) higher level of phosphorylated GSK3β (by 189%, p < 0.05). In conclusion, PANX1 ATP-permeable channels are involved in the regulation of muscle atrophic processes by modulating expression of E3 ligases, and protein translation and elongation processes during unloading

ctDNA-based detection of molecular residual disease in stage I-III non-small cell lung cancer patients treated with definitive radiotherapy

BackgroundSensitive and reliable biomarkers for early detection of recurrence are needed to improve post-definitive radiation risk stratification, disease management, and outcomes for patients with unresectable early-stage or locally advanced non-small cell lung cancer (NSCLC) who are treated with definitive radiation therapy (RT). This prospective, multistate single-center, cohort study investigated the association of circulating tumor DNA (ctDNA) status with recurrence in patients with unresectable stage I-III NSCLC who underwent definitive RT.MethodsA total of 70 serial plasma samples from 17 NSCLC patients were collected before, during, and after treatment. A personalized, tumor-informed ctDNA assay was used to track a set of up to 16 somatic, single nucleotide variants in the associated patient’s plasma samples.ResultsPre-treatment ctDNA detection rate was 82% (14/17) and varied based on histology and stage. ctDNA was detected in 35% (6/17) of patients at the first post-RT timepoint (median of 1.66 months following the completion of RT), all of whom subsequently developed clinical progression. At this first post-RT time point, patients with ctDNA-positivity had significantly worse progression-free survival (PFS) [hazard ratio (HR): 24.2, p=0.004], and ctDNA-positivity was the only significant prognostic factor associated with PFS (HR: 13.4, p=0.02) in a multivariate analysis. All patients who developed clinical recurrence had detectable ctDNA with an average lead time over radiographic progression of 5.4 months, and post-RT ctDNA positivity was significantly associated with poor PFS (p&lt;0.0001).ConclusionPersonalized, longitudinal ctDNA monitoring can detect recurrence early in patients with unresectable NSCLC patients undergoing curative radiation and potentially risk-stratify patients who might benefit most from treatment intensification

Proceedings of the 24th Paediatric Rheumatology European Society Congress: Part three

From Springer Nature via Jisc Publications Router.Publication status: PublishedHistory: collection 2017-09, epub 2017-09-0

Ideals and anti-ideals students of the basic and senior school

The paper is devoted to the study of representations of the ideals and anti-ideals in secondary and high schools students. The study is important due to connection with the peculiarities of modern adolescent socialization in the context of contemporary social cultural realities. Shaping the world view in students is significantly influenced by the choice of values and the social role model. In this regard, the aim of this study was to examine gender and age dynamics of different groups of personalities related to the politics and spiritual culture in the structure of ideals and anti-idials in modern adolescents. Aggravation of the internal and external political situation, politically-oriented media content and society as a whole, the introduction of information technologies in various spheres of life, the «western» background of cultural values and information environment, the shift of sex-role identification has a significant influence on gender-specific and age-specific dynamics and significance of different groups of personalities in the structure of ideals and anti-idials in modern adolescents are based on the data of content analysis and a questionnaire survey of 2,273 students, grades 5-11. The features of the structure of ideals and anti-idials of boys and girls, which are formed under the influence of gender identification are characterized. The analysis of the students’ groups of ideals and anti-idials is held depending on their belonging to the Russian and foreign cultures. The students’ representations of the ideals and anti-idials are of a mixed structure, dominated by the personalities of the real people in comparison with the images (characters of works of literature, cinema, cartoons). The sphere of political culture and ideology (politicians, historical figures) that presents male personalities is significant for boys. For girls, besides politics, the literary field (writers and movie actors) is more important, where the proportion of male staff increases substantially when getting on years. Analysis of ideals and anti-idials representation of «male» and «female» characters in the literary and artistic field has allowed to confirm the trend identified in previous studies: getting on years girls more and more build an image of themselves in positive samples, choosing the «female» characters as perfect role model. The «male» characters are often referred by girls among their anti-idials

Attitude to supplementary education in students of the secondary and high school: social and psychological aspects

Background. The research of the student attitude to the system of supplementary education is of paramount importance as it is the system of supplementary education where the adolescent tries to implement specific «cultural tests» that allow him/her to obtain an inverse social reaction regarding his/her personal success (success as a subject of activity). The objectives of the research are as follows: 1. Determining the influence of age, social demographic factors on the involvement of adolescents in the system of supplementary education is the objective of the research. 2. Defining the motives determining the occupations of students of the secondary and high schools in the circles, studios, sections. 3. Studying the influence of the student involement in the system of supplementary education on their studies. Research Progress. The paper presents the results of the research carried out by the Center for the Sociology of Education of the IEM RAE in October-November, 2017. The sample includes 11,803 school students of 7-11th grades of the Leningrad region, Russia. Questions concerning the student involvement in the system of supplementary education, paid vs free school classes in various circles, studios, sections, preferences of certain areas of supplementary education, variety of motives that make students get interested in different types of extra classes are discussed. The influence of extra classes on the studying activities (academic success, student status in the classroom, peculiarities of motives involved). Research Results. In the system of supplementary education, every second student of the secondary and high school is engaged. The educational status and financial position of the student’s parents influence his/her involvement in the system of supplementary education. The influence of macro-indicators (settlement factor) is marked as preference in the field of studies and also within the payment strategy of the educational services provided. Among the main motives for attending classes there are the following ones: broadening the horizons, assessing the abilities and opportunities. Conclusion. The most important motive that causes adolescent interest in various types of jobs and occupations in the system of supplementary education is to catch up with the lack of knowledge obtained in school. The student’s involvement in the system of supplementary education also sets a positive vector for his/her development as subject of the studying activity

Experimental Modeling of Natural Processes of Nepheline Alteration

Nepheline, ideally Na3K(Al4Si4O16) is a key mineral of silica-undersaturated igneous rocks. Under subsolidus conditions, nepheline is intensively replaced by numerous secondary minerals, of which various zeolites (mainly natrolite, analcime, gonnardite), as well as cancrinite, muscovite and Al-O-H phases (gibbsite, böhmite, nordstrandite) are the most common. In the rocks of the Lovozero alkaline massif (Kola Peninsula, NW Russia), nepheline is extensively replaced by the association natrolite + nordstrandite ± böhmite ± paranatrolite. To reproduce the conditions for the formation of such a mineral association, a series of experiments were carried out on the dissolution of nepheline in deionized water, 0.5 mol/L NaCl, 0.5 mol/L NaOH, and 0.1 mol/L HCl at 230 °C for 1/5/15 days. When nepheline is partially dissolved, phases and mixtures of phases precipitate on the surface of its grains, and these phases were diagnosed using X-ray powder diffraction and Raman spectroscopy. Observations in natural samples and experimental studies have shown that the nepheline alteration in the rocks of the Lovozero massif with the formation of natrolite and Al-O-H phases occurred under the influence of a high to medium salinity solution at a pH of near 6

Проявления агрессии в подростковой среде

The article discusses the peculiar features of physical aggression among adolescents and the main motives that encourage them to resort to violence. It is based on the materials obtained by the researchers of the Center for Sociology of Education of the Institute of Education Management of the Russian Academy of Education in the course of an anonymous questionnaire survey of 2983 students in grades 7, 9 and 11 of Moscow schools. The analysis of the influence of gender, age, and social stratification factors reveals motivational dominants that determine the characteristic features of the adolescents’ participation in fights depending on gender and age. Special focus is given to physical aggression in the walls of an educational organization, and namely the prevalence of fights on school grounds and the adolescents’ opinions about their teachers’ reactions to fights between their students. A fairly high level of prevalence of fights among girls indicates a significant deformation of traditional gender-role behaviors in the adolescent subculture. The research results in the conclusion that manifestations of physical aggression are related to both social mechanisms of the adolescent subculture functioning and mental characteristics of adolescenceВ статье рассматриваются особенности проявлений физической агрессии среди подростков и основные мотивы, побуждающие подростков прибегать к насилию. В основу статьи легли материалы, полученные сотрудниками Центра социологии образования «Института управления образованием Российской академии образования» в ходе анонимного анкетного опроса 2983 учащихся 7, 9 и 11 классов московских школ. В ходе анализа влияния гендерных, возрастных и социально-стратификационных факторов выделены мотивационные доминанты, определяющие особенности участия подростков в драках в зависимости от пола и возраста. Особое внимание уделяется рассмотрению проявлений физической агрессии в стенах образовательной организации, а именно распространенности драк на территории школы и мнениям учащихся о реакции их учителей на возникающие между подростками драки. Достаточно высокий уровень распространенности драк среди девочек свидетельствует о существенной деформации традиционных полоролевых моделей поведения в подростковой субкультуре. Полученные результаты позволяют сделать вывод о том, что проявления физической агрессии связаны как с социальными механизмами функционирования подростковой субкультуры, так и с психическими особенностями подросткового возраст

Improvement of In Vitro Seed Germination and Micropropagation of Amomum tsao-ko (Zingiberaceae Lindl.)

Black cardamom (Amomum tsao-ko Crevost &amp; Lemari&eacute;) is a spice plant of great commercial value in Vietnam, but with limited propagation ability. Its seeds are characterized by a thick and hard seed coat, a small endosperm, and a small embryo, which are the causes of the physical dormancy of the seeds and low germination. Attempts in this study to improve the germination rate and achieve uniform germination included mechanical scarification, immersion in hot or cold water, acid scarification, and the application of plant growth regulators. Although immersion of seeds in cold water and application of plant growth regulators (PGRs) (gibberellic acid (GA3) and 1-naphtaleneacetic acid (NAA)) showed positive effects on seed germination and subsequent seedling growth, mechanical scarification provided the highest germination rate of black cardamom seeds (68.0%) and significantly shortened germination time (53.7 days) compared to control (16.0% and 74.7 days). On the other hand, an efficient micropropagation protocol has been established using shoot tip explants derived from in-vitro-grown seedlings. Murashige and Skoog (MS) medium supplemented with 4.0 mg/L 6-benzylaminopurine (BAP) + 0.5 mg/L NAA proved to be most suitable for rapid multiplication and rooting, providing a mean of 5.4 shoots per explant, 6.8 cm shoot length, and 16.2 roots per explant after 7 weeks of culture. Well-rooted black cardamom plantlets have been successfully adapted to ex vitro conditions. &ldquo;Fasco&rdquo; bio-soil was more suitable for acclimatization, with a 48.9% survival rate, 23.3 cm plant length, and 5.7 leaves per plant after 3 months of planting. Improved germination and multiplication protocols can be used to improve propagation performances and to develop elite of black cardamom planting material

The Use of Tocilizumab in 40 Patients With Polyarticular Juvenile Idiopathic Arthritis: the Results of a Retrospective Study

The issue of a therapy of children with juvenile idiopathic arthritis (JIA) with intolerance or insufficient effectiveness of methotrexate remains actual.Objective: Our aim was to study the efficacy and safety of tocilizumab in patients with polyarticular JIA.Methods. In a retrospective study, we studied the results of the use of tocilizumab in patients with active polyarticular JIA ( 5 active joints) resistant to prior therapy with methotrexate or a combination of methotrexate with other nonbiologic disease-modifying antiinflammatory drugs.Results. The data of 40 children (83% girls) with the onset median of polyarticular JIA of 4.8 (2.9, 8.1) years and the interval between the disease onset and the initiation of tocilizumab therapy of 5.7 (1.8, 8.5) years was analyzed. Tocilizumab was used as an intravenous infusion of 8 mg/kg (with a weight 30 kg) or 10 mg/kg (with a weight &lt; 30 kg) every 4 weeks. The duration of tocilizumab monotherapy in 5 (13%) children was 1,109 days (452; 1,542). The stages of inactive disease (according to the criteria of C. Wallace, 2004) in 6 months of tocilizumab therapy reached 6 (15%) patients, in 42 months — 32 (80%) patients. In 3 patients, tocilizumab was canceled due to persistent remission. After 6 months of treatment, there was a marked decrease in erythrocyte sedimentation rate, C-reactive protein concentration, number of leukocytes and platelets (in all cases, p &lt; 0.001) to normal values, which persisted throughout the whole period of drug administration. Predictors for achieving inactive disease were the initial (at the onset of tocilizumab therapy) number of peripheral blood leukocytes &lt; 9.0X109/l [relative risk (RR) 1.92; 95% confidence interval (CI) 0.9–4.6)] and the absence of prior biological therapy (RR 1.92, 95% CI 0.9–4.6). The most frequent side effects of tocilizumab therapy were transient hypercholesterolemia (in 13), hypertriglyceridemia (in 4), transient grade II neutropenia (in 1).Conclusion. The long-term efficacy and relative safety of tocilizumab in children with polyarticular JIA have been showed