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Взаимосвязь использования цифровых устройств и эмоционально-личностного развития современных дошкольников
No full textОбращается внимание на то, что новая социальная ситуация развития детей дошкольного возраста, связанная с их повсеместной вовлеченностью в использование электронных информационных устройств с раннего возраста, становится крайне важной темой, требующей анализа взаимосвязанности включенности детей дошкольного возраста в цифровую среду и их развития в эмоционально-личностной сфере.Представлен анализ 65 исследований, проведенных в период с 2010 по 2020 гг., посвященных влиянию контента и «экранного времени» на эмоционально-личностное развитие современных дошкольников.Показано, что несоответствующий возрасту контент значимо связан с повышением уровня агрессивного и понижением уровня просоциального поведения.В то время как соответствующий возрасту качественный образовательный контент может способствовать развитию просоциального поведения и социальных навыков.Кроме того, показано, что длительное «экранное время» может увеличивать уровень агрессивного поведения и уменьшать уровень развития просоциального поведения, социальных навыков и познавательных аспектов эмоционально-личностного развития
Legal regulation of personalized medicine in the agricultural sector: the experience of Russia
No full textThis study’s topic’s relevance is due to the rapid development of genetic research, when diagnostics, prevention, and treatment are carried out through the study of nucleic acids and their expression products − RNA and proteins. Predictive (personalized) medicine (PMM) has become a preventive trend in molecular medicine, understood in different ways. However, its generally accepted features recognize the individual nature of treatment (each person’s genome is individual). The prophylactic focus of medicine (analysis of the genome is possible at any stage of ontogenesis, long before the disease’s onset) is very important. In carrying out genetic certification, the need to find a legal solution to existing or projected problems is actualized. Legal science is designed to address the issues of protecting human rights in the process of genetic certification, countering discrimination, and other possible violations of constitutional values. The issues raised in the article acquire particular importance in the context of the covid-19 pandemic. Mobility and speed of decision-making require an appropriate legal approach to telemedicine, which will provide the population with high-quality and professional medical care. Besides, it seems reasonable to observe the balance of human rights and freedoms when using the institution of genetic certification and telemedicin
Sulfur modification in natural RNA and therapeutic oligonucleotides
No full textIn this review, we highlight the importance of sulfur modifications in natural cellular RNAs and therapeutic nucleic acids. Sulfur modifications on RNA confer structural diversity, stability and enhance its functionality.
Sulfur modifications have been discovered on both DNA and RNA. Sulfur substitution of oxygen atoms at nucleobase or backbone locations in the nucleic acid framework led to a wide variety of sulfur-modified nucleosides and nucleotides. While the discovery, regulation and functions of DNA phosphorothioate (PS) modification, where one of the non-bridging oxygen atoms is replaced by sulfur on the DNA backbone, are important topics, this review focuses on the sulfur modification in natural cellular RNAs and therapeutic nucleic acids. The sulfur modifications on RNAs exhibit diversity in terms of modification location and cellular function, but the various sulfur modifications share common biosynthetic strategies across RNA species, cell types and domains of life. The first section reviews the post-transcriptional sulfur modifications on nucleobases with an emphasis on thiouridine on tRNA and phosphorothioate modification on RNA backbones, as well as the functions of the sulfur modifications on different species of cellular RNAs. The second section reviews the biosynthesis of different types of sulfur modifications and summarizes the general strategy for the biosynthesis of sulfur-containing RNA residues. One of the main goals of investigating sulfur modifications is to aid the genomic drug development pipeline and enhance our understandings of the rapidly growing nucleic acid-based gene therapies. The last section of the review focuses on the current drug development strategies employing sulfur substitution of oxygen atoms in therapeutic RNAs
P27 Bedside teaching from a distance; surgical education in the COVID era, a randomised control trial
No full textAbstract Introduction The COVID pandemic resulted in a shutdown of facilities and resources globally. With drastic changes in the provision of services available in the health sector, so too were medical students’ provision of learning. With the onslaught of COVID and the need for ongoing learning resources for students, novel methods to maintain adequate surgical patient exposure and student interaction on a platform amenable to the interactive format required was devised using a virtual platform to compliment current pedagogical approaches. Methods This was a randomised control trial to evaluate the perceived use of remote learning in place of surgical bedside teaching in the COVID-19 era. Medical students in a regional hospital were recruited and randomised to undergo the bedside teaching in person or receive the teaching virtually through a Xpert eye, smart glasses to facilitate connections remotely. Feedback questionnaires and exit interviews carried out following each session. Content analysis of transcripts was performed to evaluate the presence and quality of perceived learning, benefits and limitations. Results Feedback demonstrated greater engagement, satisfaction, involvement and learning (p < 0.01) in the bedside teaching group. Content analysis yielded three main themes; Interpersonal content, technological features, and provision of content. Students reported the virtual teaching was an acceptable alternative in the current climate of social distancing and reduced patient access. Conclusion The current pandemic poses a risk to adequate patient exposure to patient centred learning. Teaching sessions received remotely are an acceptable alternative in the current climate of reduced clinical access, however bedside teaching remains the preferred method of learning
Hydroxychloroquine in patients with novel coronavirus infection (COVID-19): a case-control study.
No full textActuality One of the most widely discussed treatments for patients with COVID-19, especially at the beginning of the epidemy, was the use of the antimalarial drug hydroxychloroquine (HCQ). The first small non-randomized trials showed the ability of HCQ and its combination with azithromycin to accelerate the elimination of the virus and ease the acute phase of the disease. Later, large, randomized trials did not confirm it (RECOVERY, SOLIDARITY). This study is a case-control study in which we compared patients who received and did not receive HCQ.Material and Methods 103 patients (25 in the HCQ treatment group and 78 in the control group) with confirmed COVID-19 (SARS-CoV-2 virus RNA was detected in 26 of 73 in the control group (35.6%) and in 10 of 25 (40%) in the HCQ group) and in the rest - a typical picture of viral pneumonia on multislice computed tomography [MSCT]) were included in the analysis. The severity of lung damage was limited to stages I-II, the CRP level should not exceed 60 mg/dL, and oxygen saturation in the air within 92-98%. We planned to analysis the duration of treatment of patients in the hospital, the days until the normalization of body temperature, the number of points according to the original SHOCS-COVID integral scale, and changes in its components (C-reactive protein (CRP), D-dimer, and the percentage of lung damage according to MSCT).Results Analysis for the whole group revealed a statistically significant increase in the time to normalization of body temperature from 4 to 7 days (by 3 days,
Process-based approach to organizing the accounting of labor costs and motivation in the digital economy
No full textThe article discusses the main risks of accounting for settlements with personnel in modern conditions, including those caused by significant changes in legislation, in terms of regulating the procedure for implementing expenses for labor remuneration. The authors systematized the main risks pursuant to a number of basic accounting criteria: purpose, order, content. The proposed approach, in contrast to the existing approaches, allows to quickly segment problematic risk areas of work in accounting. The article presents the characteristics of accounting procedures in the course of reflecting operations related to the accrual, retention and payment of wages, considering the conditions of digital transformation, where, in contrast to the existing approaches, the aspects of the influence of endo- and exogenous factors in the dynamics of the development of digital transformations are systematized. The content of IAS 19 Employee Benefits has been structured by different types of benefits. The criteria for recognizing the fact of remuneration are considered, a critical assessment of the classification and approaches to different types of remuneration in the context of noonomics is given
Graft-versus-Host Disease Prophylaxis with Post-Transplantation Bendamustine in Patients with Refractory Acute Leukemia: A Dose-Ranging Study
No full textThe prognosis of acute leukemia refractory to induction chemotherapy or immunotherapy is dismal. Salvage allogeneic hematopoietic stem cell transplantation (HSCT) is widely used option for these patients, but only 10% to 15% of patients are cured by the procedure. Preclinical studies indicate that substitution of post-transplantation cyclophosphamide with bendamustine (PTB) in a prophylaxis regimen may be associated with an augmented graft-versus-leukemia (GVL) reaction. The aim of this study was to establish the optimal dose of PTB and evaluate the antileukemic effect of HSCT with this type of graft-versus-host disease (GVHD) prophylaxis. In the prospective trial (NCT02799147), PTB was administered in doses of 140, 100, and 70 mg/m2 on days +3 and +4. Myeloablative conditioning with fludarabine and oral busulfan was provided to all patients. The first 12 patients received single-agent PTB, and subsequent patients received combination therapy with tacrolimus and mycophenolate mofetil (MMF). Inclusion criteria were acute myelogenous leukemia (AML) or acute lymphoblastic leukemia (ALL) refractory to at least one induction course of chemotherapy or target therapy and ≥5% clonal blasts in the bone marrow. The study cohort comprised 22 patients with AML and 5 with ALL. Seven patients were enrolled in the 140 mg/m2 group (due to a stopping rule), and 10 each were enrolled in the 100 mg/m2 and 70 mg/m2 groups. Primary refractory disease was documented in 41% of the patients, and secondary refractory was documented in 59%. The median blast count in the bone marrow at the start of the conditioning was 18% (range, 6% to 97%). Transplantation was performed with a matched sibling donor in 5 patients, a matched or mismatched unrelated donor in 15, and a haploidentical donor in 7. Engraftment was documented in 93% of the patients, including 89% with complete remission and 63% without measurable residual disease. After PTB prophylaxis, we observed an unusual complication, a cytokine release syndrome (CRS), in 70% of the patients, including grade 3 to 5 CRS in 44%. The most frequent clinical symptoms included high fever in 67% of patients, abnormal liver function tests in 67%, pancreatitis in 63%, skin vasculitis in 56%, enterocolitis in 48%, inflammation of oral mucosa in 37%, disseminated intravascular coagulation in 37%, and central nervous system toxicity in 26%. The development of CRS was associated with use of an HLA-mismatched donor (75% versus 20%; P = .0043). Classic acute GVHD was documented in 44% of the patients. Grade II-IV acute GVHD was associated with grade 3 to 5 CRS (67% versus 25%; P = .031). Moderate and severe chronic GVHD in the 100-day survivors were more often observed after single-agent PTB than after the combination immunosuppression (100% versus 18%; P = .002). A relatively low relapse rate was observed for this patient population. Three-year overall survival was 28% (95% confidence interval [CI], 13% to 46%), and event-free survival was 29% (95% CI, 13% to 46%). Nonrelapse mortality was 46% (95% CI, 25% to 64%), and the cumulative incidence of relapse was 26% (95% CI, 11% to 44%). No relapses were documented after day +100. There were no statistically significant differences among the dose groups (P = .3481); however, survival was higher in the 100 mg/kg group. Survival was higher in patients with AML compared with those with ALL (35% versus 0%; P = .0157). PTB represents a promising option to augment the GVL effect in refractory AML; however, the high CRS-associated mortality necessitates additional studies to reduce the risk of this complication. Thus, routine clinical application of PTB cannot be currently recommended. Combination immunosuppression with tacrolimus and MMF partially ameliorates these complications, at least in the setting of HLA-matched allografts. Biological mechanisms of CRS and GVL after PTB require further elucidation
Ineffectiveness of COVID-19 therapy: causes and possible remedies
No full textThe article provides a literature review of our own clinical studies, which summarizes data on the diversity of pathogenetic mechanisms of damage to various organs and systems in coronavirus disease 2019 (COVID-19). The predominance of one or another injury creates various clinical types, each of which requires specific approaches to therapy. The effectiveness of treatment regimens with direct-acting antiviral drugs is currently absolutely proven, however, the patient’s recovery time, the prevalence of complications and adverse outcomes depend not only on causal therapy, but also on the correct selection of pathogenetic and symptomatic therapy
Molecular dynamics analysis of N-acetyl-D-glucosamine against specific SARS-CoV-2’s pathogenicity factors
No full textThe causative agent of the pandemic identified as SARS-CoV-2 leads to a severe respiratory illness similar to SARS and MERS with fever, cough, and shortness of breath symptoms and severe cases that can often be fatal. In our study, we report our findings based on molecular docking analysis which could be the new effective way for controlling the SARS-CoV-2 virus and additionally, another manipulative possibilities involving the mimicking of immune system as occurred during the bacterial cell recognition system. For this purpose, we performed molecular docking using computational biology techniques on several SARS-CoV-2 proteins that are responsible for its pathogenicity against N-acetyl-D-glucosamine. A similar molecular dynamics analysis has been carried out on both SARS-CoV-2 and anti-Staphylococcus aureus neutralizing antibodies to establish the potential of N-acetyl-D-glucosamine which likely induces the immune response against the virus. The results of molecular dynamic analysis have confirmed that SARS-CoV-2 spike receptor-binding domain (PDB: 6M0J), RNA-binding domain of nucleocapsid phosphoprotein (PDB: 6WKP), refusion SARS-CoV-2 S ectodomain trimer (PDB: 6X79), and main protease 3clpro at room temperature (PDB: 7JVZ) could bind with N-acetyl-D-glucosamine that these proteins play an important role in SARS-CoV-2's infection and evade the immune system. Moreover, our molecular docking analysis has supported a strong protein-ligand interaction of N-acetyl-D-glucosamine with these selected proteins. Furthermore, computational analysis against the D614G mutant of the virus has shown that N-acetyl-D-glucosamine affinity and its binding potential were not affected by the mutations occurring in the virus' receptor binding domain. The analysis on the affinity of N-acetyl-D-glucosamine towards human antibodies has shown that it could potentially bind to both SARS-CoV-2 proteins and antibodies based on our predictive modelling work. Our results confirmed that N-acetyl-D-glucosamine holds the potential to inhibit several SARS-CoV-2 proteins as well as induce an immune response against the virus in the host
C21 preserves endothelial function in the thoracic aorta from DIO mice: role for AT2, Mas and B2 receptors
No full textCompound 21 (C21), a selective agonist of angiotensin II type 2 receptor (AT2R), induces vasodilation through NO release. Since AT2R seems to be overexpressed in obesity, we hypothesize that C21 prevents the development of obesity-related vascular alterations. The main goal of the present study was to assess the effect of C21 on thoracic aorta endothelial function in a model of diet-induced obesity (DIO) and to elucidate the potential cross-talk among AT2R, Mas receptor (MasR) and/or bradykinin type 2 receptor (B2R) in this response. Five-week-old male C57BL6J mice were fed a standard (CHOW) or a high-fat diet (HF) for 6 weeks and treated daily with C21 (1 mg/kg p.o) or vehicle, generating four groups: CHOW-C, CHOW-C21, HF-C, HF-C21. Vascular reactivity experiments were performed in thoracic aorta rings. Human endothelial cells (HECs; EA.hy926) were used to elucidate the signaling pathways, both at receptor and intracellular levels. Arteries from HF mice exhibited increased contractions to Ang II than CHOW mice, effect that was prevented by C21. PD123177, A779 and HOE-140 (AT2R, Mas and B2R antagonists) significantly enhanced Ang II-induced contractions in CHOW but not in HF-C rings, suggesting a lack of functionality of those receptors in obesity. C21 prevented those alterations and favored the formation of AT2R/MasR and MasR/B2R heterodimers. HF mice also exhibited impaired relaxations to acetylcholine (ACh) due to a reduced NO availability. C21 preserved NO release through PKA/p-eNOS and AKT/p-eNOS signaling pathways. In conclusion, C21 favors the interaction among AT2R, MasR and B2R and prevents the development of obesity-induced endothelial dysfunction by stimulating NO release through PKA/p-eNOS and AKT/p-eNOS signaling pathways