Safety and Availability of Clofazimine in the Treatment of Multidrug and Extensively Drug-Resistant Tuberculosis: Analysis of Published Guidance and Meta-Analysis of Cohort Studies

Objectives: Given the spread of multidrug-resistant tuberculosis (MDR-TB), new therapies are urgently needed, including the repurposing of existing drugs. We aimed to assess key considerations for the clinical and programmatic use of clofazimine (Cfz), a riminophenazine with anti-mycobacterial activity currently used to treat leprosy. Design: Fixed and random effects meta-analysis of cohort studies and systematic review Setting: Electronic and manual searches were combined. Inclusion criteria: Observational studies on treatment of multidrug- and extremely drug- resistant tuberculosis with clofazimine or a clofazimine-containing regimen, and published guidance and documents relating to cost and availability were eligible. Results: Five observational studies enrolled 861 patients, of which 602 received Cfz. The pooled proportion of adverse drug reactions requiring discontinuation of Cfz treatment was 0.1% (95% CI: [0.0, 0.6%]), and the median frequency of all adverse events was 5.1%. Cfz showed in vitro efficacy against Mycobacterium tuberculosis, and Cfz-containing regimens may have had a useful role in the treatment of patients with drug-resistant strains and who had limited alternative treatment options. However, Cfz uptake remains insufficient to meet global needs; there is only one internationally quality-assured manufacturer, which produces a limited quantity of the drug prioritised for treatment of leprosy, the only indication for which the drug is registered. Conclusions: While the data were limited, Cfz was associated with a risk for adverse drug reactions comparable to that of first-line TB treatment, which could be reasonably managed under programmatic conditions. However, low market availability and high cost are important barriers to access to Cfz for MDR-TB patients.Other Research Uni

Національна доповідь про стан і перспективи розвитку освіти в Україні: монографія (До 30-річчя незалежності України)

The publication provides a comprehensive analysis of the state and development of national education over the 30 years of Ukraine’s independence, identifies current problems in education, ascertains the causes of their emergence, offers scientifically reasoned ways to modernise domestic education in the context of globalisation, European integration, innovative development, and national self-identification. Designed for legislators, state officials, education institutions leaders, teaching and academic staff, the general public, all those who seek to increase the competitiveness of Ukrainian education in the context of civilisation changes.У виданні здійснено всебічний аналіз стану і розвитку національної освіти за 30-річний період незалежності України, визначено актуальні проблеми освітньої сфери, виявлено причини їх виникнення, запропоновано науково обґрунтовані шляхи модернізації вітчизняної освіти в умовах глобалізації, європейської інтеграції, інноваційного розвитку та національної самоідентифікації. Розраховано на законодавців, державних управлінців, керівників закладів освіти, педагогічних і науково-педагогічних працівників, широку громадськість, усіх, хто прагне підвищення конкурентоспроможності української освіти в контексті цивілізаційних змін

Ecologization of Regional Industrial Complex in the Transition to Sustainable Development

Ensuring the sustainable development of a country or a single territory is a complex task, the main role in the implementation of which is the timely receipt of financial resources. This allows for the implementation of innovative economic and environmental policies aimed at diversification and ecologization of the regional economy, including a reduction in the negative impact on the environment, the introduction of new technologies at enterprises, the strengthening of environmental expertise and the consideration of the environmental factor in making managerial decisions, population and other activities. The regions became able to pursue an environmental policy only in the conditions of boosting the innovative activity in the leading industries. Together with the consolidation of environmental funds, this must be the main reason for efficient financing of environmental policy. So ecologization of industrial region economy means environmentalization of its economic development

Zero Waste Technologies and Solution of Economic and Environmental Problems of Sustainable Development

Economic and environmental problems are closely related, and solving some of them, the others cannot be solved. The state of the environment directly forms the potential of the economic sphere. For example, resources for industrial enterprises are formed in the natural environment, and the capacity of plants and factories depends on resources’ quantity. The amount of money to be spent on the purchase and installation of treatment plants, on the measures to eliminate water, air and soil pollution, depends upon the profit. Each country has its own list of environmental problems related to the economy. They are engaged in their elimination at the state level, but first of all the responsibility for the consequences is the burden of companies’ management. The active development of the economy should not adversely affect the state of the environment. Both individual enterprises and whole states should control the economic and environmental situation in order to achieve a balance and solve global problems. The most important form of interaction between the state and business in solving economic-and-environmental problems is the introduction of zero waste technologies in all their diversity and achieving their multiplicative effect. The paper shows the relationship between environmentally-oriented innovative development of the economy and the introduction of zero waste technologies

Structural Inertia as a Constraint for Sustainable Development and Interregional Differences in Quality of Life Reducing

Inertia is an attribute of various systems, including sustainable development. The study of the inertia of sustainable development as a complex industrial-ecological and socio-economic supersystems is necessary to give due depth to theoretical explanations of the processes implemented in the practice of regulating industrial production, economic relations that determine the environmental load, the level of consumption of natural resources, to identify qualitative and quantitative relationships between factors of changes in structural proportions in production and consumption, their sources and relocation productive forces. The result if the study of inertia as a quality of macroeconomic structural changes, immanent to sustainable development, should be a knowledge of the forms of the transition of economic achievements of society into environmental ones. The study of sustainable development inertia is intended to improve the forecasting of various processes of interaction between man and the environment through the use of productive forces. The content of structural inertia of sustainable development can be revealed through the dynamic and actively transforming properties of structural shifts no less than through the conservatism of the structure of the economy, therefore, the creation of conditions for the regulated implementation of structural inertia, its transition into its opposite – acceleration of positive structural transformations – is associated with the regulation of economic relations in the system of environment management, production and consumption of natural resources, dynamization of changes in structural proportions between raw materials production and its processing, to overcome delaying the formation of new structural elements

Institutional Traps and Externalities of Sustainable Development of the Mining Country in Transition to Digital and Knowledge Economy

The content, boundaries, development vector and expected results of the sustainable development policy today rightfully belong to one of the most debated issues in the scientific community. The imperative of solving the critical problem of replacing the dominant world order based on the extraction of mineral raw materials carries the risk of increasing economic isolationism. This threatens to eliminate the economics of extracting products from technological production chains that meet the needs of modern consumers around the world, and the loss of technological identity of the industry. For the transition of an economy with a developed commodity sector to the path of sustainable development, modernization of industry on a new technological basis is required and saturation of the domestic market with environmentally friendly production requires, on the one hand, the import of technologies, and on the other, significant “environmental technologies connected” investments. Therefore, sustainable development should be both a goal and, at the same time, the result of a new industrialization of the economy, cannot set itself the goal of enhancing isolation from the global raw materials market

The effect of TLR3 priming conditions on MSC immunosuppressive properties

Abstract Background Mesenchymal stromal cells (MSCs) have regenerative and immunomodulatory properties, making them suitable for cell therapy. Toll-like receptors (TLRs) in MSCs respond to viral load by secreting immunosuppressive or proinflammatory molecules. The expression of anti-inflammatory molecules in MSCs can be altered by the concentration and duration of exposure to the TLR3 ligand polyinosinic-polycytidylic acid (poly(I:C)). This study aimed to optimize the preconditioning of MSCs with poly(I:C) to increase immunosuppressive effects and to identify MSCs with activated TLR3 (prMSCs). Methods Flow cytometry and histochemical staining were used to analyze MSCs for immunophenotype and differentiation potential. MSCs were exposed to poly(I:C) at 1 and 10 μg/mL for 1, 3, and 24 h, followed by determination of the expression of IDO1, WARS1, PD-L1, TSG-6, and PTGES2 and PGE2 secretion. MSCs and prMSCs were cocultured with intact (J−) and activated (J+) Jurkat T cells. The proportion of proliferating and apoptotic J+ and J− cells, IL-10 secretion, and IL-2 production after cocultivation with MSCs and prMSCs were measured. Liquid chromatography–mass spectrometry and bioinformatics analysis identified proteins linked to TLR3 activation in MSCs. Results Poly(I:C) at 10 μg/mL during a 3-h incubation caused the highest expression of immunosuppression markers in MSCs. Activation of prMSCs caused a 18% decrease in proliferation and a one-third increase in apoptotic J+ cells compared to intact MSCs. Cocultures of prMSCs and Jurkat cells had increased IL-10 and decreased IL-2 in the conditioned medium. A proteomic study of MSCs and prMSCs identified 53 proteins with altered expression. Filtering the dataset with Gene Ontology and Reactome Pathway revealed that poly(I:C)-induced proteins activate the antiviral response. Protein‒protein interactions by String in prMSCs revealed that the antiviral response and IFN I signaling circuits were more active than in native MSCs. prMSCs expressed more cell adhesion proteins (ICAM-I and Galectin-3), PARP14, PSMB8, USP18, and GBP4, which may explain their anti-inflammatory effects on Jurkat cells. Conclusions TLR3 activation in MSCs is dependent on exposure time and poly(I:C) concentration. The maximum expression of immunosuppressive molecules was observed with 10 µg/mL poly(I:C) for 3-h preconditioning. This priming protocol for MSCs enhances the immunosuppressive effects of prMSCs on T cells

Formation of a Thin Continuous GaSb Film on Si(001) by Solid Phase Epitaxy

Nanocrystalline GaSb films were grown on Si(001) from the stoichiometric Ga⁻Sb mixture using solid-phase epitaxy at temperatures of 200⁻500 °C. Use of the solid-phase epitaxy method allowed the suppression of Ga surface diffusion and prevention of intense Sb desorption. At the annealing temperature of 300 °C, a 14-nm-thick GaSb film aggregates, while a 20-nm-thick GaSb film remains continuous with a roughness of 1.74 nm. A GaSb film with a thickness of 20 nm consists of crystalline grains with a size of 9⁻16 nm. They were compressed by ~2%. For some GaSb grains, new epitaxial relationships have been found: GaSb ( 111 ) ||Si ( 11 1 ¯ ) and GaSb [ 11 2 ¯ ] ||Si [ 1 1 ¯ 0 ] , GaSb ( 113 ) ||Si ( 11 1 ¯ ) and GaSb [ 1 1 ¯ 0 ] ||Si [ 1 1 ¯ 0 ] , and GaSb ( 11 1 ¯ ) ||Si ( 002 ) and GaSb [ 1 1 ¯ 0 ] ||Si [ 1 1 ¯ 0 ]