The system of knowledge control as a challenge to distance education

Having signed the Bologna declaration in the fall of 2003, Russian Federation has directed towards unified standards of education. Information technologies are gaining more and more popularity, particularly the systems of distance education (SDE) are of greater interest. It may well be assumed such systems will become an inseparable part of the educational process. With the rise of popularity for distance education there appears the issue for the quality and control of knowledge in such a system of learning. The authors of the article have attempted to summarize the existing experience in Baikal International Business School in terms of goals, functions and challenges of the system of knowledge control in the SDE of BIBS HecademОсенью 2003 года, подписав Болонскую декларацию, Российская Федерация вступила на путь унификации стандартов образования. Информационные технологии набирают растущую популярность, в частности системы дистанционного обучения представляют наибольший интерес. С большой долей вероятности можно предположить, что такие системы станут неотъемлемой частью образовательного процесса. С постоянно растущей популярностью дистанционного образования возникает вопрос качества и контроля знаний в такой системе обучения. Авторы статьи предприняли попытку описать существующий опыт Байкальской Международной Бизнес Школы и представляют цели, функции и проблемы системы контроля знаниями в системе дистанционного обучения БМБШ Гекаде

Clonal expansion of T memory stem cells determines early anti-leukemic responses and long-term CAR T cell persistence in patients

Low-affinity CD19 chimeric antigen receptor (CAR) T cells display enhanced expansion and persistence, enabling fate tracking through integration site analysis. Here we show that integration sites from early (1 month) and late (>3 yr) timepoints cluster separately, suggesting different clonal contribution to early responses and prolonged anti-leukemic surveillance. CAR T central and effector memory cells in patients with long-term persistence remained highly polyclonal, whereas diversity dropped rapidly in patients with limited CAR T persistence. Analysis of shared integrants between the CAR T cell product and post-infusion demonstrated that, despite their low frequency, T memory stem cell clones in the product contributed substantially to the circulating CAR T cell pools, during both early expansion and long-term persistence. Our data may help identify patients at risk of early loss of CAR T cells and highlight the critical role of T memory stem cells both in mediating early anti-leukemic responses and in long-term surveillance by CAR T cells

Long-term lymphoid progenitors independently sustain naïve T and NK cell production in humans.

Our mathematical model of integration site data in clinical gene therapy supported the existence of long-term lymphoid progenitors capable of surviving independently from hematopoietic stem cells. To date, no experimental setting has been available to validate this prediction. We here report evidence of a population of lymphoid progenitors capable of independently maintaining T and NK cell production for 15 years in humans. The gene therapy patients of this study lack vector-positive myeloid/B cells indicating absence of engineered stem cells but retain gene marking in both T and NK. Decades after treatment, we can still detect and analyse transduced naïve T cells whose production is likely maintained by a population of long-term lymphoid progenitors. By tracking insertional clonal markers overtime, we suggest that these progenitors can support both T and NK cell production. Identification of these long-term lymphoid progenitors could be utilised for the development of next generation gene- and cancer-immunotherapies

Aberrant chromatin landscape following loss of the H3.3 chaperone Daxx in haematopoietic precursors leads to Pu.1-mediated neutrophilia and inflammation

Defective silencing of retrotransposable elements has been linked to inflammageing, cancer and autoimmune diseases. However, the underlying mechanisms are only partially understood. Here we implicate the histone H3.3 chaperone Daxx, a retrotransposable element repressor inactivated in myeloid leukaemia and other neoplasms, in protection from inflammatory disease. Loss of Daxx alters the chromatin landscape, H3.3 distribution and histone marks of haematopoietic progenitors, leading to engagement of a Pu.1-dependent transcriptional programme for myelopoiesis at the expense of B-cell differentiation. This causes neutrophilia and inflammation, predisposing mice to develop an autoinflammatory skin disease. While these molecular and phenotypic perturbations are in part reverted in animals lacking both Pu.1 and Daxx, haematopoietic progenitors in these mice show unique chromatin and transcriptome alterations, suggesting an interaction between these two pathways. Overall, our findings implicate retrotransposable element silencing in haematopoiesis and suggest a cross-talk between the H3.3 loading machinery and the pioneer transcription factor Pu.1

ЗНАЧЕНИЕ ИНТЕГРИРОВАННОГО ЛЕГОЧНОГО ИНДЕКСА В ОЦЕНКЕ ТЯЖЕСТИ ТЕЧЕНИЯ ПОСЛЕОПЕРАЦИОННОГО ПЕРИОДА ПРИ АОРТОКОРОНАРНОМ ШУНТИРОВАНИИ НА РАБОТАЮЩЕМ СЕРДЦЕ

Forty patients after elective off-pump coronary artery bypass grafting (OPCAB) were enrolled into a prospective observational study and monitored using SpO2, EtCO2, pulse rate and respiratory rate. In addition, the Integrated Pulmonary Index (IPI, CapnostreamTM 20p, Covidien) was registered prior tracheal extubation and at 2, 6, 12, and 18 hrs after extubation. The hemodynamics was monitored using continuous non-invasive cardiac index (esCCO, Nihon Kohden) and left ventricular ejection fraction (EF) before and after the intervention. The value of IPI registered during the respiratory support correlated with cardiac index (p = 0.04). In the subgroup of the patients with IPI below 8 at 2 hrs after extubation, we found lower ejection fraction (p = 0.007). In addition, the IPI value ≤ 9 was a predictor of complicated early postoperative period (AUC = 0,7; p = 0, 04). Thus, IPI reflects the hemodynamic status and the course of postoperative stay after OPCAB. У 40 пациентов после аортокоронарного шунтирования (АКШ) на работающем сердце на фоне респираторной поддержки и после экстубации трахеи осуществляли мониторинг газового состава артериальной крови, SpO2 , EtCO2 , частоты дыханий, частоты пульса и интегрированного легочного индекса (IPI, CapnostreamTM 20p, Covidien). Мониторинг показателей гемодинамики включал непрерывную регистрацию сердечного индекса (СИ) (esCCO, Nihon Kohden) и оценку фракции изгнания левого желудочка (ФИлж) до и после операции. Значение IPI, зарегистрированное на фоне респираторной поддержки в отделении реанимации, коррелировало с СИ (p = 0,04), а значение IPI <  8 через 2 ч после экстубации ассоциировалось с более низкой ФИлж после операции (p = 0,007). Кроме того, значения IPI < 8 через 2 ч после экстубации ассоциировалось с более низкой ФИлжпосле операции (p = 0,007). Кроме того, значения IPI ≤ 9 через 6 ч после экстубации трахеи выступили как пре- диктор осложненного течения раннего послеоперационного периода (AUC = 0,7 p = 0,04). Таким образом, показатель IPI отражает состояние гемодинамики и тяжесть течения послеоперацион- ного периода при АКШ на работающем сердце. Ключевые слова: послеоперационная дыхательная недостаточность, аортокоронарное шунтирование, мониторинг.>≤  9 через 6 ч после экстубации трахеи выступили как пре- диктор осложненного течения раннего послеоперационного периода (AUC = 0,7 p = 0,04). Таким образом, показатель IPI отражает состояние гемодинамики и тяжесть течения послеоперационного периода при АКШ на работающем сердце.

Lentiviral gene therapy for X-linked chronic granulomatous disease

Chronic granulomatous disease (CGD) is a rare inherited disorder of phagocytic cells. We report the initial results of nine severely affected X-linked CGD (X-CGD) patients who received ex vivo autologous CD34+ hematopoietic stem and progenitor cell-based lentiviral gene therapy following myeloablative conditioning in first-in-human studies (trial registry nos. NCT02234934 and NCT01855685). The primary objectives were to assess the safety and evaluate the efficacy and stability of biochemical and functional reconstitution in the progeny of engrafted cells at 12 months. The secondary objectives included the evaluation of augmented immunity against bacterial and fungal infection, as well as assessment of hematopoietic stem cell transduction and engraftment. Two enrolled patients died within 3 months of treatment from pre-existing comorbidities. At 12 months, six of the seven surviving patients demonstrated stable vector copy numbers (0.4–1.8 copies per neutrophil) and the persistence of 16–46% oxidase-positive neutrophils. There was no molecular evidence of either clonal dysregulation or transgene silencing. Surviving patients have had no new CGD-related infections, and six have been able to discontinue CGD-related antibiotic prophylaxis. The primary objective was met in six of the nine patients at 12 months follow-up, suggesting that autologous gene therapy is a promising approach for CGD patients

Adequate antibiotic therapy of acute edematous infiltrative laryngitis

The article reviews prevalence and pathogens of acute edematous infiltrative laryngitis based on the national and foreign literature. The most common antibiotic drugs that are used for the treatment of acute edematous infiltrative laryngitis of different etiologies, including their dosage, are specified. Treatment recommendations are proposed

Antibiotic therapy of acute inflammatory diseases of the upper respiratory tract infections in pregnant women

The challenge posed by acute inflammatory diseases of the upper respiratory tract (URT) is obvious. According to national and foreign specialists, from 0.5 to 6% of cases of ARVI are complicated by bacterial infection of the paranasal sinuses, and up to 15% - acute otitis media [1, 2]. Among patients seeking medical help from ENT specialist, pregnant women are a special category due to the difficulty of selection of an appropriate therapy

Problems of therapy of acute purulent rhinosinusitis

Acute sinusitis (AS) continues to be a challenge in the present-day otorhinolaryngology, occupying a leading place in the structure of inflammatory diseases of the upper respiratory tract. Thus, patients with sinus disorders account for 15 to 36% of all patients at ENT units. The crucial aspect in the treatment of acute sinusitis is achieving persistent bactericidal concentration of antibiotic resulting in the desired eradication of the bacteria

Use of second-generation antihistamines in combination treatment of ENT diseases

Currently, allergic diseases are very widespread, and their incidence is increasing at an alarming pace worldwide. [1] According to different authors, from 20 to 50% of the population in European countries suffer from allergic diseases. Large-scale epidemiological studies demonstrated that 20% of the population at least once in their lives had acute urticaria. [2,