Distance learning in higher education Russia

Одной из наиболее распространенных и доступных форм обучения в последние годы стало дистанционное обучение. Дистанционное обучение сориентировано на территориальную удаленность преподавателя и студента и осуществляется с использованием современных информационных и телекоммуникационных технологий. Дистанционное обучение дает возможность индивидуализации высшего образования, построения индивидуальной образовательной траектории.Distance learning is one of the most widespread and accessible forms of education in the recent years. Distance learning is focused on the territorial remoteness of the teacher and the student and is implemented using modern information and telecommunication technologies. Distance learning provides an opportunity for individualization of higher education, the construction of an individual educational trajectory

Влияние лития хлорида на активацию нейтрофилов под действием сыворотки пациентов с септическим шоком

The aim of the study: to examine the anti-inflammatory effect of lithium chloride by exposing the human neutrophils to serum of patients with septic shock in vitro.Material and methods. The study was carried out on neutrophils extracted from the blood of 6 healthy donors, which were activated with serum from patients with septic shock. The neutrophil activity was evaluated with fluorescent antibodies to the CD11b and CD66b markers of degranulation. The level of human neutrophil apoptosis and necrosis was assessed 22 hours after extraction; quantitative assessment was made using annexin V and propidium iodide with flow cytofluorimetry. Intact and activated neutrophils were treated with 0.3, 3.0 and 9.0 mmol lithium chloride solution.Results. The level of CD11b expression on the surface of intact neutrophils (healthy donors) was 3434.50 [3311.0-3799.0] arbitrary fluorescence units (AFU). Incubation of neutrophils with serum of patients with septic shock increased CD11b expression 2.5 times to 8589.0 [7279.0-11258.0] AFU (P=0.005) vs intact leukocytes, and increased CD66b expression 2.7 times up to 27 600.0 [22 999.0-28 989.0] AFU ((P=0.005) vs intact neutrophils. Lithium chloride in concentrations of 0.3, 3.0 and 9.0 mmol in a dose-dependent manner reduced the level of expression of CD11b and CD66b molecules on the surface of activated neutrophils. Septic serum reduced spontaneous neutrophil apoptosis, and 3.0 mmol and higher lithium chloride solution induced spontaneous neutrophil apoptosis.Conclusion. Lithium chloride reduces the activation of neutrophils preactivated by serum of patients with septic shock, reduces expression of CD11b and CD66b molecules on the neutrophil surface, inhibiting the process of their activation (degranulation). Lithium chloride in concentration of 3.0 mmol and higher is able to induce spontaneous apoptosis of neutrophils activated by serum of patients with septic shock.Цель исследования — изучить противовоспалительное действие хлорида лития путем воздействия на нейтрофилы человека сыворотки пациентов с септическим шоком in vitro.Материал и методы. Исследование проводили на выделенных из крови 6 здоровых доноров нейтрофилах, которые активировали с помощью сыворотки пациентов с септическим шоком, после чего оценивали их активность с помощью флуоресцентных антител к маркерам дегрануляции CD11b и CD66b. Уровень апоптоза и некроза нейтрофилов человека оценивали через 22 часа после выделения; количественная оценка была проведена с использованием аннексина V и йодистого пропидия на проточном цитофлуориметре. Интактные и активированные нейтрофилы обрабатывали раствором хлорида лития в концентрациях 0,3; 3,0 и 9 ммоль.Результаты. Уровень экспрессии CD11b на поверхности интактных нейтрофилов (здоровые доноры) составил 3434,50 [3311,0-3799,0] условных единиц флуоресценции (у.е.ф.). Инкубация нейтрофилов с сывороткой крови пациентов с септическим шоком увеличивала экспрессию CD11b в 2,5 раза — 8589,0 [7279,0-11258,0] у.е.ф. (р=0,005) в сравнении с интактными лейкоцитами, и увеличивала экспрессию CD66b в 2,7 раза до 27 600,0 [22 999,0-28 989,0] у.е.ф. (р=0,005) в сравнении с интактными нейтрофилами. Лития хлорид дозозависимо в концентрациях — 0,3 ммоль, 3,0 и 9,0 ммоль снижал уровень экспрессии молекул CD11b и CD66b на поверхности активированных нейтрофилов. Септическая сыворотка уменьшала спонтанный апоптоз нейтрофилов, а раствор лития хлорида в дозе 3 ммоль и выше индуцировал спонтанный апоптоз нейтрофилов.Заключение. Хлорид лития снижает степень активации нейтрофилов, предварительно активированных сывороткой пациентов с септическим шоком, снижает уровень экспрессии молекул CD11b и CD66b на поверхности нейтрофилов, ингибируя процесс их активации (дегрануляции). Лития хлорида в концентрации 3 ммоль и выше способен индуцировать спонтанный апоптоз нейтрофилов, активированных сыворотками пациентов с септическим шоком

mRNA-binding protein tristetraprolin is essential for cardiac response to iron deficiency by regulating mitochondrial function.

細胞質における鉄の出納はiron regulatory protein 1および2（IRP1/2）を介する鉄輸送の制御によって維持されるが，鉄が重要な役割を果たすミトコンドリアにおける鉄欠乏への適応機構は不明であった．本研究では，mRNA結合蛋白tristetraprolin（TTP）が鉄欠乏により発現誘導され，ミトコンドリア電子伝達系における鉄含有蛋白の発現量を鉄利用に合わせて適切に制御することによりミトコンドリア機能を維持することを明らかにした

Impact of renal impairment on atrial fibrillation: ESC-EHRA EORP-AF Long-Term General Registry

Background: Atrial fibrillation (AF) and renal impairment share a bidirectional relationship with important pathophysiological interactions. We evaluated the impact of renal impairment in a contemporary cohort of patients with AF. Methods: We utilised the ESC-EHRA EORP-AF Long-Term General Registry. Outcomes were analysed according to renal function by CKD-EPI equation. The primary endpoint was a composite of thromboembolism, major bleeding, acute coronary syndrome and all-cause death. Secondary endpoints were each of these separately including ischaemic stroke, haemorrhagic event, intracranial haemorrhage, cardiovascular death and hospital admission. Results: A total of 9306 patients were included. The distribution of patients with no, mild, moderate and severe renal impairment at baseline were 16.9%, 49.3%, 30% and 3.8%, respectively. AF patients with impaired renal function were older, more likely to be females, had worse cardiac imaging parameters and multiple comorbidities. Among patients with an indication for anticoagulation, prescription of these agents was reduced in those with severe renal impairment, p <.001. Over 24 months, impaired renal function was associated with significantly greater incidence of the primary composite outcome and all secondary outcomes. Multivariable Cox regression analysis demonstrated an inverse relationship between eGFR and the primary outcome (HR 1.07 [95% CI, 1.01–1.14] per 10 ml/min/1.73 m2 decrease), that was most notable in patients with eGFR <30 ml/min/1.73 m2 (HR 2.21 [95% CI, 1.23–3.99] compared to eGFR ≥90 ml/min/1.73 m2). Conclusion: A significant proportion of patients with AF suffer from concomitant renal impairment which impacts their overall management. Furthermore, renal impairment is an independent predictor of major adverse events including thromboembolism, major bleeding, acute coronary syndrome and all-cause death in patients with AF

Clinical complexity and impact of the ABC (Atrial fibrillation Better Care) pathway in patients with atrial fibrillation: a report from the ESC-EHRA EURObservational Research Programme in AF General Long-Term Registry

Background: Clinical complexity is increasingly prevalent among patients with atrial fibrillation (AF). The ‘Atrial fibrillation Better Care’ (ABC) pathway approach has been proposed to streamline a more holistic and integrated approach to AF care; however, there are limited data on its usefulness among clinically complex patients. We aim to determine the impact of ABC pathway in a contemporary cohort of clinically complex AF patients. Methods: From the ESC-EHRA EORP-AF General Long-Term Registry, we analysed clinically complex AF patients, defined as the presence of frailty, multimorbidity and/or polypharmacy. A K-medoids cluster analysis was performed to identify different groups of clinical complexity. The impact of an ABC-adherent approach on major outcomes was analysed through Cox-regression analyses and delay of event (DoE) analyses. Results: Among 9966 AF patients included, 8289 (83.1%) were clinically complex. Adherence to the ABC pathway in the clinically complex group reduced the risk of all-cause death (adjusted HR [aHR]: 0.72, 95%CI 0.58–0.91), major adverse cardiovascular events (MACEs; aHR: 0.68, 95%CI 0.52–0.87) and composite outcome (aHR: 0.70, 95%CI: 0.58–0.85). Adherence to the ABC pathway was associated with a significant reduction in the risk of death (aHR: 0.74, 95%CI 0.56–0.98) and composite outcome (aHR: 0.76, 95%CI 0.60–0.96) also in the high-complexity cluster; similar trends were observed for MACEs. In DoE analyses, an ABC-adherent approach resulted in significant gains in event-free survival for all the outcomes investigated in clinically complex patients. Based on absolute risk reduction at 1 year of follow-up, the number needed to treat for ABC pathway adherence was 24 for all-cause death, 31 for MACEs and 20 for the composite outcome. Conclusions: An ABC-adherent approach reduces the risk of major outcomes in clinically complex AF patients. Ensuring adherence to the ABC pathway is essential to improve clinical outcomes among clinically complex AF patients

Impact of clinical phenotypes on management and outcomes in European atrial fibrillation patients: a report from the ESC-EHRA EURObservational Research Programme in AF (EORP-AF) General Long-Term Registry

Background: Epidemiological studies in atrial fibrillation (AF) illustrate that clinical complexity increase the risk of major adverse outcomes. We aimed to describe European AF patients\u2019 clinical phenotypes and analyse the differential clinical course. Methods: We performed a hierarchical cluster analysis based on Ward\u2019s Method and Squared Euclidean Distance using 22 clinical binary variables, identifying the optimal number of clusters. We investigated differences in clinical management, use of healthcare resources and outcomes in a cohort of European AF patients from a Europe-wide observational registry. Results: A total of 9363 were available for this analysis. We identified three clusters: Cluster 1 (n = 3634; 38.8%) characterized by older patients and prevalent non-cardiac comorbidities; Cluster 2 (n = 2774; 29.6%) characterized by younger patients with low prevalence of comorbidities; Cluster 3 (n = 2955;31.6%) characterized by patients\u2019 prevalent cardiovascular risk factors/comorbidities. Over a mean follow-up of 22.5 months, Cluster 3 had the highest rate of cardiovascular events, all-cause death, and the composite outcome (combining the previous two) compared to Cluster 1 and Cluster 2 (all P <.001). An adjusted Cox regression showed that compared to Cluster 2, Cluster 3 (hazard ratio (HR) 2.87, 95% confidence interval (CI) 2.27\u20133.62; HR 3.42, 95%CI 2.72\u20134.31; HR 2.79, 95%CI 2.32\u20133.35), and Cluster 1 (HR 1.88, 95%CI 1.48\u20132.38; HR 2.50, 95%CI 1.98\u20133.15; HR 2.09, 95%CI 1.74\u20132.51) reported a higher risk for the three outcomes respectively. Conclusions: In European AF patients, three main clusters were identified, differentiated by differential presence of comorbidities. Both non-cardiac and cardiac comorbidities clusters were found to be associated with an increased risk of major adverse outcomes

The loss of P2X7 receptor expression leads to increase intestinal glucose transit and hepatic steatosis

In intestinal epithelial cells (IEC), it was reported that the activation of the P2X7 receptor leads to the internalization of the glucose transporter GLUT2, which is accompanied by a reduction of IEC capacity to transport glucose. In this study, we used P2rx7−/− mice to decipher P2X7 functions in intestinal glucose transport and to evaluate the impacts on metabolism. Immunohistochemistry analyses revealed the presence of GLUT2 at the apical domain of P2rx7−/− jejunum enterocytes. Positron emission tomography and biodistribution studies demonstrated that glucose was more efciently delivered to the circulation of knockout animals. These fndings correlated with increase blood glucose, insulin, triglycerides and cholesterol levels. In fact, P2rx7−/− mice had increased serum triglyceride and cholesterol levels and displayed glucose intolerance and resistance to insulin. Finally, P2rx7−/− mice developed a hepatic steatosis characterized by a reduction of Acaca, Acacb, Fasn and Acox1 mRNA expression, as well as for ACC and FAS protein expression. Our study suggests that P2X7 could play a central role in metabolic diseases

The Effect of Lithium Chloride on Neutrophil Activation on Exposure to Serum of Patients with Septic Shock

The aim of the study: to examine the anti-inflammatory effect of lithium chloride by exposing the human neutrophils to serum of patients with septic shock in vitro.Material and methods. The study was carried out on neutrophils extracted from the blood of 6 healthy donors, which were activated with serum from patients with septic shock. The neutrophil activity was evaluated with fluorescent antibodies to the CD11b and CD66b markers of degranulation. The level of human neutrophil apoptosis and necrosis was assessed 22 hours after extraction; quantitative assessment was made using annexin V and propidium iodide with flow cytofluorimetry. Intact and activated neutrophils were treated with 0.3, 3.0 and 9.0 mmol lithium chloride solution.Results. The level of CD11b expression on the surface of intact neutrophils (healthy donors) was 3434.50 [3311.0-3799.0] arbitrary fluorescence units (AFU). Incubation of neutrophils with serum of patients with septic shock increased CD11b expression 2.5 times to 8589.0 [7279.0-11258.0] AFU (P=0.005) vs intact leukocytes, and increased CD66b expression 2.7 times up to 27 600.0 [22 999.0-28 989.0] AFU ((P=0.005) vs intact neutrophils. Lithium chloride in concentrations of 0.3, 3.0 and 9.0 mmol in a dose-dependent manner reduced the level of expression of CD11b and CD66b molecules on the surface of activated neutrophils. Septic serum reduced spontaneous neutrophil apoptosis, and 3.0 mmol and higher lithium chloride solution induced spontaneous neutrophil apoptosis.Conclusion. Lithium chloride reduces the activation of neutrophils preactivated by serum of patients with septic shock, reduces expression of CD11b and CD66b molecules on the neutrophil surface, inhibiting the process of their activation (degranulation). Lithium chloride in concentration of 3.0 mmol and higher is able to induce spontaneous apoptosis of neutrophils activated by serum of patients with septic shock