Pedagogical conditions of primary drug abuse prevention among students of a higher education institution

The relevance of the researched problem is caused by the fact that being one of the least adapted and socially unprotected groups, young people bear the impress of general social uncertainty, lack of confidence and uneasiness, as a result of it, drug addiction problems among young people are pushed into the forefront among social-pedagogical and psychological-pedagogical problems. The purpose of the presented article consists in theoretical reasons, development experimental and research check of a complex of the pedagogical conditions providing efficiency of primary prevention of drug addiction among students of a higher education institution. The leading method to a research of this problem is the modeling method that enables to consider this problem as a purposeful and organized process of creation of the pedagogical conditions necessary for effective primary prevention of drug addiction among students of a higher education institution. The complex of the pedagogical conditions providing efficiency of process of primary drug abuse prevention is presented in the article. It consists of the pedagogical analysis of the reasons of a drug abuse, detection of specifics of a drug abuse of youthful age, the choice and use of the methods and agents of primary prophylaxis of a youth drug abuse, development of a special course for training of specialists which are carrying out activities for prophylaxis of the drug habit at educational organizations. The complex of pedagogical conditions is focused on the process organization of drug abuse prevention among students and focused on development of methodical ensuring process of training of the teachers who are carrying out activities for drug abuse prevention in educational organizations. The materials of article can be useful to teachers of higher education institutions and colleges participating in the organization and carrying out preventive measures of a drug addiction, and also to the listeners, graduates of military academies, and practical staffof Department of Internal Affairs of the Russian Federation who are interested in drug addiction problems. © Authors

Implementation of contact interaction in a finite - element formulation

© 2014 O. A. Sachenkov, V. I. Mitryaikin, T. A. Zaitseva and Yu. G. Konoplev. The paper presents a technique which makes it possible to take into account contact interactions between surfaces based on the finite element method. The technique is based on iterative cycles, determining statuses of the contact elements and renewing the contact forces to satisfy the condition of zero penetration of all active contact elements. The proposed technique allows us also to take account of friction between the contacting elements. The paper considers an example of implementing contact interaction with regard to friction between bodies, and solves a model problem

Targeting BTK for the treatment of FLT3-ITD mutated acute myeloid leukemia

Approximately 20% of patients with acute myeloid leukaemia (AML) have a mutation in FMS-like-tyrosine-kinase-3 (FLT3). FLT3 is a trans-membrane receptor with a tyrosine kinase domain which, when activated, initiates a cascade of phosphorylated proteins including the SRC family of kinases. Recently our group and others have shown that pharmacologic inhibition and genetic knockdown of Bruton's tyrosine kinase (BTK) blocks AML blast proliferation, leukaemic cell adhesion to bone marrow stromal cells as well as migration of AML blasts. The anti-proliferative effects of BTK inhibition in human AML are mediated via inhibition of downstream NF-κB pro-survival signalling however the upstream drivers of BTK activation in human AML have yet to be fully characterised. Here we place the FLT3-ITD upstream of BTK in AML and show that the BTK inhibitor ibrutinib inhibits the survival and proliferation of FLT3-ITD primary AML blasts and AML cell lines. Furthermore ibrutinib inhibits the activation of downstream kinases including MAPK, AKT and STAT5. In addition we show that BTK RNAi inhibits proliferation of FLT3-ITD AML cells. Finally we report that ibrutinib reverses the cyto-protective role of BMSC on FLT3-ITD AML survival. These results argue for the evaluation of ibrutinib in patients with FLT3-ITD mutated AML

RANGING THE KHABAROVSK KRAY TERRITORIES BY THE LEVELS OF DYSENTERY EPIDEMIC MANIFESTATIONS

Aim: to reveal the Khabarovsk region territories that are under high risk of spread of dysentery in the period of large-scale flood fallout liquidation. Materials and methods. There was the analysis conducted of dysentery incidence during the period of 2003-2012 including distribution of annual and long-term annual average indicators per 100 000 inhabitants throughout administrative entities of Khabarovsk territory. We used methods that reveal tendencies and evaluated dynamic rates of dysentery epidemic process in time. Results and discussion. Khabarovsk region shows uneven levels of manifestations of epidemic process of dysentery not only during evaluation of annual incidence but also among certain administrative territories. During ten years preceding the flood in the Amur River region, long-term annual average level of incidence equaled to 42.7 ± 1.740/0000 The epidemic process was most intense in the Nanayi region, in other six administrative regions long-term annual average levels of incidence were exceeding similar averaged levels in Khabarovsk region. An intense epidemiologic situation on dysentery in several territories of the region was associated with registration of foci of clustered incidence caused by dysentery Sonne of alimentary and water-borne origin including atypical variants of Shigella Sonne. Conclusion. A year before the flood the elevation of dysentery incidence was registered in most of the territories of Khabarovsk Kray, and there was the evidence of outlined tendency of activation of epidemic process. This served as a basis for required adequate emergency measures for prophylaxis of dysentery

Течение Covid-19 у вакцинированных пациентов

Aim of study. To conduct a retrospective analysis of treatment outcomes for COVID-19 in unvaccinated and vaccinated patients.Material and methods. The present retrospective single-center study included 209 patients who were vaccinated in history and hospitalized at the City Aleksandrovskaya Hospital for infection with COVID-19 in the period from April 5, 2020 to July 9, 2021. The average period between vaccine administration and hospitalization was 18.0 ± 11.0 days. In all cases, a positive result of the polymerase chain reaction (PCR) for the presence of SARS-CoV-2 was obtained. These patients were included in Group 1. The comparison group included 475 unvaccinated patients with comparable lung tissue damage according to multispiral computed tomography of the chest (MSCT) and a positive PCR result for the presence of SARS-CoV-2, selected randomly over the same observation period.Results. The lesions of the lung tissue according to the results of chest MSCT upon admission of the group were comparable (p=0.55). All deaths were observed in the group of unvaccinated patients (n=46; 9.7%; p<0.0001). In all cases, the cause was an increase in multiple organ failure. In the same cohort of patients, there was a statistically significantly greater number of deep vein thrombosis of the upper and lower extremities (p=0.02). In the group of vaccinated patients (1st), arterial thrombosis of various location was not diagnosed, while in the 2nd group (comparison), this pathology was detected in every 10th patient. At the same time, thrombosis of the arteries of the lower extremities developed statistically more often (n=52; 10.9%; p><0.0001). This condition was accompanied by an increase in laboratory parameters of the inflammatory reaction and coagulopathy with the progression of lung tissue damage to the 3–4th degree according to the results of MSCT. However, in 37 (7.8%) cases, open thrombectomy was not possible, and on the first day after the operation, repeated thrombosis developed, followed by amputation of the limb. In 23 (4.8%) cases, a fatal outcome was observed. Conclusion Vaccination prevents the severe course of covid-19: the progression of pneumonia, coagulopathy, and inflammatory syndrome. In vaccinated patients, no deaths, pulmonary embolism were observed, which demonstrates the absence of a severe course of the disease. All arterial thrombosis associated with covid-19 develops in unvaccinated patients and is accompanied by a high incidence of repeated thrombosis, requiring subsequent amputation of the limb. The widespread introduction of vaccination will help reduce the severity of the course and prevent complications of the new coronavirus infection. Key words: COVID-19, novel coronavirus infection, thrombosis, SARS-CoV-2, vaccine>˂0.0001). In all cases, the cause was an increase in multiple organ failure. In the same cohort of patients, there was a statistically significantly greater number of deep vein thrombosis of the upper and lower extremities (p=0.02). In the group of vaccinated patients (1st), arterial thrombosis of various location was not diagnosed, while in the 2nd group (comparison), this pathology was detected in every 10th patient. At the same time, thrombosis of the arteries of the lower extremities developed statistically more often (n=52; 10.9%; p˂0.0001). This condition was accompanied by an increase in laboratory parameters of the inflammatory reaction and coagulopathy with the progression of lung tissue damage to the 3–4th degree according to the results of MSCT. However, in 37 (7.8%) cases, open thrombectomy was not possible, and on the first day after the operation, repeated thrombosis developed, followed by amputation of the limb. In 23 (4.8%) cases, a fatal outcome was observed.Conclusion. Vaccination prevents the severe course of covid-19: the progression of pneumonia, coagulopathy, and inflammatory syndrome. In vaccinated patients, no deaths, pulmonary embolism were observed, which demonstrates the absence of a severe course of the disease. All arterial thrombosis associated with covid-19 develops in unvaccinated patients and is accompanied by a high incidence of repeated thrombosis, requiring subsequent amputation of the limb. The widespread introduction of vaccination will help reduce the severity of the course and prevent complications of the new coronavirus infection. Цель. Провести ретроспективный анализ исходов лечения COVID-19 у невакцинированных и вакцинированных пациентов.Материал и методы. В настоящее ретроспективное одноцентровое исследование вошли 209 пациентов, вакцинированных и госпитализированных в СПб ГБУЗ «Городская Александровская больница» по поводу заражения COVID-19 в период с 5 апреля 2021 по 9 июля 2021 г. Средний период между введением вакцины и госпитализацией составил 18,0±11,0 суток. Во всех случаях был получен положительный результат полимеразной цепной реакции (ПЦР) на наличие SARS-CoV-2. Данные пациенты были включены в 1-ю (основную) группу. В группу сравнения вошли 475 невакцинированных больных с сопоставимым поражением легочной ткани по данным мультиспиральной компьютерной томографии органов грудной клетки (МСКТ ОГК) и положительным результатом ПЦР на наличие SARS-CoV-2, подобранных рандомизированным способом за тот же период наблюдения.Результаты. Поражения легочной ткани согласно результатам МСКТ ОГК на момент поступления группы были сопоставимы (р=0,55). Все смертельные исходы были зафиксированы в группе невакцинированных пациентов (n=46; 9,7%; р<0,0001, статистически значимо). Во всех случаях причиной стало нарастание полиорганной недостаточности. В этой же когорте больных отмечалось статистически значимо большее количество тромбозов глубоких вен верхних и нижних конечностей (р=0,02). В группе вакцинированных пациентов (1-я) артериальные тромбозы разной локализации не диагностировались, тогда как во 2-й группе (сравнения) данная патология была выявлена у каждого 10-го больного. При этом статистически значимо чаще развивался тромбоз артерий нижних конечностей (n=52; 10,9%; р><0,0001). Данное состояние сопровождалось нарастанием лабораторных показателей воспалительной реакции и коагулопатией с прогрессированием поражения легочной ткани до 3–4-й степени по результатам МСКТ. Однако в 37 случаях (7,8%) открытая тромбэктомия оказалась невозможной, и в первые сутки после операции развился повторный тромбоз с последующей ампутацией конечности. В 23 случаях (4,8%) был зафиксирован смертельный исход. Заключение Вакцинация предупреждает тяжелое течение COVID-19: прогрессирование пневмонии, коагулопатии и воспалительного синдрома. У вакцинированных пациентов не наблюдалось смертельных исходов, тромбоэмболии легочной артерии, что демонстрирует отсутствие тяжелого течения заболевания. Все артериальные тромбозы на фоне COVID-19 развиваются у невакцинированных пациентов и сопровождаются высокой частотой повторных тромбозов, требующих последующей ампутации конечности. Широкое внедрение вакцинации будет способствовать уменьшению тяжести течения и профилактике осложнений новой коронавирусной инфекции. Ключевые слова: COVID-19, новая коронавирусная инфекция, тромбоз, SARS-CoV-2, вакцина >˂ 0,0001, статистически значимо). Во всех случаях причиной стало нарастание полиорганной недостаточности. В этой же когорте больных отмечалось статистически значимо большее количество тромбозов глубоких вен верхних и нижних конечностей (р=0,02). В группе вакцинированных пациентов (1-я) артериальные тромбозы разной локализации не диагностировались, тогда как во 2-й группе (сравнения) данная патология была выявлена у каждого 10-го больного. При этом статистически значимо чаще развивался тромбоз артерий нижних конечностей (n=52; 10,9%; р˂ 0,0001). Данное состояние сопровождалось нарастанием лабораторных показателей воспалительной реакции и коагулопатией с прогрессированием поражения легочной ткани до 3–4-й степени по результатам МСКТ. Однако в 37 случаях (7,8%) открытая тромбэктомия оказалась невозможной, и в первые сутки после операции развился повторный тромбоз с последующей ампутацией конечности. В 23 случаях (4,8%) был зафиксирован смертельный исход.Заключение. Вакцинация предупреждает тяжелое течение COVID-19: прогрессирование пневмонии, коагулопатии и воспалительного синдрома. У вакцинированных пациентов не наблюдалось смертельных исходов, тромбоэмболии легочной артерии, что демонстрирует отсутствие тяжелого течения заболевания. Все артериальные тромбозы на фоне COVID-19 развиваются у невакцинированных пациентов и сопровождаются высокой частотой повторных тромбозов, требующих последующей ампутации конечности. Широкое внедрение вакцинации будет способствовать уменьшению тяжести течения и профилактике осложнений новой коронавирусной инфекции.

Preliminary study on the utilization of Ca2+ and HCO3 − in karst water by different sources of Chlorella vulgaris

This article aims to present a picture of how a university discipline has been created in Lithuania, given the background of changes caused by the Lithuania’s emancipation from the Soviet Union. The theoretical frame of reference is provided by a modified model of Bronfenbrenners developmental ecology. Data collection has primarily been in the form of interviews with university staff from Lithuanian institutions for higher education. In addition to the interviews, literature lists, course schedules and other key documents have been collected and analysed. The analysis focuses on individual’s conceptualisation of three main areas. The study demonstrates how the creation of management and economics as a university discipline in Lithuania has been formed by a combination of political/ideological, economic, institutional and individual factors. One of the study’s main contributions is to highlight the significance of the concept of academic freedom and to focus on the paradox, where constraint under the old system is replaced by another form of constraint. In this case, where the rigidity of the old Soviet doctrine is replaced by a new freedom; but instead of being given greater opportunities to influence and change the subject, the academic staff are forced into a position where, once again they are subjugated to the influences of international sources

5-Methylcytosine and 5-Hydroxymethylcytosine Spatiotemporal Profiles in the Mouse Zygote

Background: In the mouse zygote, DNA methylation patterns are heavily modified, and differ between the maternal and paternal pronucleus. Demethylation of the paternal genome has been described as an active and replication-independent process, although the mechanisms responsible for it remain elusive. Recently, 5-hydroxymethylcytosine has been suggested as an intermediate in this demethylation. Methodology/principal findings: In this study, we quantified DNA methylation and hydroxymethylation in both pronuclei of the mouse zygote during the replication period and we examined their patterns on the pericentric heterochromatin using 3D immuno-FISH. Our results demonstrate that 5-methylcytosine and 5-hydroxymethylcytosine localizations on the pericentric sequences are not complementary; indeed we observe no enrichment of either marks on some regions and an enrichment of both on others. In addition, we show that DNA demethylation continues during DNA replication, and is inhibited by aphidicolin. Finally, we observe notable differences in the kinetics of demethylation and hydroxymethylation; in particular, a peak of 5-hydroxymethylcytosine, unrelated to any change in 5-methylcytosine level, is observed after completion of replication. Conclusion/significance: Together our results support the already proposed hypothesis that 5-hydroxymethylcytosine is not a simple intermediate in an active demethylation process and could play a role of its own during early development

Catalytic Mechanism of Bacteriophage T4 Rad50 ATP Hydrolysis

Spontaneous double-strand breaks (DSBs) are one of the most deleterious forms of DNA damage, and their improper repair can lead to cellular dysfunction. The Mre11 and Rad50 proteins, a nuclease and an ATPase, respectively, form a well-conserved complex that is involved in the initial processing of DSBs. Here we examine the kinetic and catalytic mechanism of ATP hydrolysis by T4 Rad50 (gp46) in the presence and absence of Mre11 (gp47) and DNA. Single-turnover and pre-steady state kinetics on the wild-type protein indicate that the rate-limiting step for Rad50, the MR complex, and the MR-DNA complex is either chemistry or a conformational change prior to catalysis. Pre-steady state product release kinetics, coupled with viscosity steady state kinetics, also supports that the binding of DNA to the MR complex does not alter the rate-limiting step. The lack of a positive deuterium solvent isotope effect for the wild type and several active site mutants, combined with pH–rate profiles, implies that chemistry is rate-limiting and the ATPase mechanism proceeds via an asymmetric, dissociative-like transition state. Mutation of the Walker A/B and H-loop residues also affects the allosteric communication between Rad50 active sites, suggesting possible routes for cooperativity between the ATP active sites

HIF1α drives chemokine factor pro-tumoral signaling pathways in acute myeloid leukemia

Approximately 80% of patients diagnosed with acute myeloid leukemia (AML) die as a consequence of failure to eradicate the tumor from the bone marrow microenvironment. We have recently shown that stroma-derived interleukin-8 (IL-8) promotes AML growth and survival in the bone marrow in response to AML-derived macrophage migration inhibitory factor (MIF). In the present study we show that high constitutive expression of MIF in AML blasts in the bone marrow is hypoxia-driven and, through knockdown of MIF, HIF1α and HIF2α, establish that hypoxia supports AML tumor proliferation through HIF1α signaling. In vivo targeting of leukemic cell HIF1α inhibits AML proliferation in the tumor microenvironment through transcriptional regulation of MIF, but inhibition of HIF2α had no measurable effect on AML blast survival. Functionally, targeted inhibition of MIF in vivo improves survival in models of AML. Here we present a mechanism linking HIF1α to a pro-tumoral chemokine factor signaling pathway and in doing so, we establish a potential strategy to target AML

Regulation of ABCC6 trafficking and stability by a conserved C-terminal PDZ-like sequence

Mutations in the ABCC6 ABC-transporter are causative of pseudoxanthoma elasticum (PXE). The loss of functional ABCC6 protein in the basolateral membrane of the kidney and liver is putatively associated with altered secretion of a circulatory factor. As a result, systemic changes in elastic tissues are caused by progressive mineralization and degradation of elastic fibers. Premature arteriosclerosis, loss of skin and vascular tone, and a progressive loss of vision result from this ectopic mineralization. However, the identity of the circulatory factor and the specific role of ABCC6 in disease pathophysiology are not known. Though recessive loss-of-function alleles are associated with alterations in ABCC6 expression and function, the molecular pathologies associated with the majority of PXE-causing mutations are also not known. Sequence analysis of orthologous ABCC6 proteins indicates the C-terminal sequences are highly conserved and share high similarity to the PDZ sequences found in other ABCC subfamily members. Genetic testing of PXE patients suggests that at least one disease-causing mutation is located in a PDZ-like sequence at the extreme C-terminus of the ABCC6 protein. To evaluate the role of this C-terminal sequence in the biosynthesis and trafficking of ABCC6, a series of mutations were utilized to probe changes in ABCC6 biosynthesis, membrane stability and turnover. Removal of this PDZ-like sequence resulted in decreased steady-state ABCC6 levels, decreased cell surface expression and stability, and mislocalization of the ABCC6 protein in polarized cells. These data suggest that the conserved, PDZ-like sequence promotes the proper biosynthesis and trafficking of the ABCC6 protein. © 2014 Xue et al