Formación de la legislación sobre el seguro de pensiones en Francia, el Reino Unido y Rusia. Una retrospectiva

The relevance of the study is due to the crisis of modern pension insurance systems and the need to change the paradigm of pension legislation development. The purpose of the study is to identify the features of the formation of legislation on pension insurance in several countries (France, Great Britain, and Russia) at the initial stage of development (before 1914). The novelty is expressed both in the formulation of the problem and in the research methodology (the choice of countries and the period of research, the justification for the use of methods: dialectics, analysis, synthesis, system-structural, sociological, statistical, historical-legal, comparative-legal, formal-legal). The result of the study was the conclusions about the historical conditionality of the peculiarities of the formation of legislation on pension insurance in a particular country. There was early legalization of both voluntary and compulsory pension insurance in France. There was no legislation on pension insurance in the UK during the period under review, despite the early development of relevant institutions in the framework of workshops, guilds, and later in the framework of trade unions and “friendly societies”. In Russia, due to the agrarian nature of the economy, pension insurance did not develop within the framework of workshops and guilds; there were no laws on insurance in case of old age by 1914, while the risks of disability and loss of the breadwinner were regulated by law.El estudio analiza la crisis de los sistemas modernos pensionales y establece la necesidad de cambiar el paradigma de la legislación de pensiones. El objetivo del estudio consiste en identificar las características de la legislación sobre los seguros pensionales de varios estados (Francia, Reino Unido y Rusia) partiendo de su etapa inicial hasta 1914. La novedad se expresa tanto en la formulación del problema como en la metodología de investigación (selección de países y período de estudio, justificación de la aplicación de los métodos: dialéctico, de análisis, de síntesis, sistémico-estructural, sociológico, estadístico, histórico-legal, comparativo-legal, formal-legal). Como resultado del estudio se llegó a conclusiones sobre el condicionamiento histórico de las características de la formación de la legislación sobre el seguro de pensiones de un país en particular. En Francia, se promulgó una legislación temprana sobre el seguro de pension voluntario y también obligatorio en Francia. En el Reino Unido, durante el período que se examina, no había legislación sobre seguros de pensiones, a pesar del desarrollo temprano de las instituciones pertinentes dentro de los talleres, gremios y, posteriormente, dentro de la actividad de los sindicatos y las «sociedades fraternales». En Rusia, debido a la naturaleza agraria de la economía, el seguro de pensiones en el marco de los talleres y gremios nunca funcionó; en 1914 se adolecía de leyes sobre el seguro de vejez, mientras que los riesgos de discapacidad y la pérdida del sostén de la familia se regulaban por ley

Idiomatic equivalents in terms of metaphoric transfer

The article presents a hermeneutic approach to idiomatic equivalents in terms of metaphoric transfer. Metaphor is viewed by the authors in its broad sense that can be applied to any use of words in an indirect meaning. Hence, an idiom is understood as a verbalized metaphor that reflects both the universal and specific features of a given language. Idiomatic equivalence that traditionally refers to the linguistic properties of the idiom is presented in the article as hermeneutic equivalence based on the thinking activity approach. Within the framework of such approach the idiomatic equivalence highlights the transfer from one culture to another way of thinking and thinking activity organization

Audiovisual content analysis in the translation process

The article presents a comprehensive approach to the process of audiovisual translation that includes application of multimodal analysis of semiotic codes present in audiovisual productions. The article dwells on how the proposed approach can be applied to analyzing audiovisual productions for different types of audiovisual translation. Due to its multimodal nature, an audiovisual production is understood by the authors as an audiovisual text that combines image, sound and verbal means, that is, different modes conveying meaning. The means of conveying meaning in an audiovisual production include the visual non-verbal elements, visual verbal elements as well as audio non-verbal and verbal elements. The priority of these means of meaning transfer and their interaction in meaning generation differ significantly depending on the genre of audiovisual productions and the specifics of the process of its creation

Structure of Erm-modified 70S ribosome reveals the mechanism of macrolide resistance

Many antibiotics inhibit bacterial growth by binding to the ribosome and interfering with protein biosynthesis. Macrolides represent one of the most successful classes of ribosome-targeting antibiotics. The main clinically relevant mechanism of resistance to macrolides is dimethylation of the 23S rRNA nucleotide A2058, located in the drug-binding site, a reaction catalyzed by Erm-type rRNA methyltransferases. Here, we present the crystal structure of the Erm-dimethylated 70S ribosome at 2.4 Å resolution, together with the structures of unmethylated 70S ribosome functional complexes alone or in combination with macrolides. Altogether, our structural data do not support previous models and, instead, suggest a principally new explanation of how A2058 dimethylation confers resistance to macrolides. Moreover, high-resolution structures of two macrolide antibiotics bound to the unmodified ribosome reveal a previously unknown role of the desosamine moiety in drug binding, laying a foundation for the rational knowledge-based design of macrolides that can overcome Erm-mediated resistance

A Convenient Way to Quinoxaline Derivatives through the Reaction of 2-(3-Oxoindolin-2-yl)-2-phenylacetonitriles with Benzene-1,2-diamines

Microwave-assisted reaction between 2-(3-oxoindolin-2-yl)-2-phenylacetonitriles andbenzene-1,2-diamines leads to the high-yielding formation of the corresponding quinoxalines as sole, easily isolaable products. The featured transformation involves unusual extrusion of phenylacetonitrile molecule and could be performed in a short sequence starting from commonly available indoles and nitroolefins

Role of hepcidin in the development of anemia in patients with rheumatoid arthritis

Chronic disease anemia (CDA) diagnosed in many patients with rheumatoid arthritis (RA) was described in the early 1970s. As earlier noted, iron metabolic disturbances in CDA are its diagnostic feature and the discovery of hepcidin, an iron-regulatory acute-phase protein, could largely clarify an association between the immune mechanism of impaired iron homeostasis and the development of CDA. Objective: to define the role of hepcidin in the differential diagnosis of CDA and true iron deficiency in patients with RA. Subjects and methods. The investigation enrolled 76 patients with RA (1987 ACR criteria) admitted to the Research Institute of Rheumatology, Russian Academy of Medical Sciences, to be treated. The patients were divided into two groups. A study group comprised anemic patients (n = 47). The WHO criteria for anemia were considered to be hemoglobin (Hb) levels of below 120 g/l for women and below 130 g/l for men. A control group consisted of non-anemic patients (n = 29). The anemic and non-anemic patients were matched for age (45.5±14.3 and 49.8±14.3 years, respectively) and disease duration (2 months to 20 years) (p > 0.05). Iron metabolic parameters, such as serum iron, total serum iron-binding capacity (TSIBC), iron transferrin saturation (ITS), transferrin receptors, and serum ferritin (SF), were studied and the level of hepcidin prohormone was estimated by direct enzyme immunoassay (Hepcidin Prohormone Enzyme Immunoassay Kit, IBL, Germany) in all the patients to be analyzed. Cytokines, such as interleukin 6, tumor necrosis factor-а) were determined by enzyme immunoassay (Bender MedSystems, Austria). The Institute’s differential diagnostic algorithm involving SF, TSIBC, and ITS was used to diagnose iron deficiency. The diagnosis was based on two stages of estimating iron values: isolated iron-deficiency anemia (IDA) was diagnosed if SF was below the normal value (< 40 μg/l). If the patient had SF of μ40 μg/l with a simultaneous rise of TSIBC above the normal level (> 70 μg/l) and a drop of ITS (> 20%), he/she might be suspected as having the mixed genesis of anemia, in which both iron deficiency and CDA are detectable. The other patients could be diagnosed as having isolated CDA. Results. The study has established that irrespective of the hemoglobin level, the content of serum hepcidin prohormone in the examined patients with RA averaged 89.2±65.1 pg/ml and was much higher than that in donors (64.9+21.6 pg/ml; р < 0.05). An analysis of the blood biochemical parameters characterizing iron metabolism showed that, whether they were anemic or non-anemic, the patients with RA, as compared with donors, were found to have an elevated level of SF that is an acute-phase indicator and reflects the high activity of an inflammatory process. To rule out IDA, the anemic patients with RA were subdivided into 3 subgroups according to the differential diagnostic algorithm. Subgroup 1 included patients with isolated CDA (n = 13 patients (28% of those in the study group)); Subgroup 2 consisted of 17 (32%) patients with anemia of mixed genesis (CDA ± IDA), and Subgroup 3 comprised 17 patients with IDA. An analysis of the clinical and laboratory parameters in RA independent of the nature of anemia demonstrated that only the patients with isolated CDA had significantly higher mean values of hepcidin prohormone (120.3±56.1 pg/ml) as compared to the control group (90.3±37.9 pg/ml) and RA patients with iron deficiency (both isolated IDA and that of mixed genesis). The same subgroup had a higher inflammatory RA activity characterized by the highest values of DAS 28, C-reactive protein, and SF. Conclusion. Hepcidin is a negative regulator of iron metabolism and may be used for the differential diagnosis of CDA and true iron deficiency in patients with RA

Роль лабораторных биомаркеров в мониторинге и прогнозировании эффективности терапии ревматических заболеваний генно-инженерными биологическими препаратами

Significant progress in treating immunoinflammatory rheumatic diseases (RD) is related to the design of a novel family of drugs, genetically engineered (GE) drugs. Molecular and cellular biomarkers (antibodies, indicators of acute inflammation, cytokines, chemokines, growth factors, endothelial activation markers, immunoglobulins, cryoglobulins, T- and B-cell subpopulations, products of bone and cartilage metabolism, genetic and metabolic markers) that allow one to conduct immunological monitoring and prediction of the effectiveness of RD therapy using tumor necrosis factor α inhibitors (infliximab, adalimumab, golimumab, etanercept), anti-B-cell drugs (rituximab, belimumab), interleukin-6 receptor antagonist (tocilizumab), and T-cell costimulation blocker (abatacept) have been detected in blood, synovial fluid, urine, and bioptates of the affected tissues. In addition to the conventional uniplex immunodiagnostics techniques, multiplex analysis of marker, which is based on genetic, transcriptomic and proteomic technologies using DNA and protein microarrays, polymerase chain reaction, and flow cytometry, is becoming increasingly widespread. The search for and validation of immunological predictors of the effective response to GE drug therapy make it possible to optimize and reduce the cost of therapy using these drugs in future.Значительный прогресс в лечении иммуновоспалительных ревматических заболеваний (РЗ) связан с разработкой нового класса лекарственных средств – генно-инженерных биологических препаратов (ГИБП). В настоящее время в крови, синовиальной жидкости, моче и биоптатах пораженных тканей выявлены молекулярные и клеточные биомаркеры (антитела, показатели острой фазы воспаления, цитокины, хемокины, факторы роста, маркеры активации эндотелия, иммуноглобулины, криоглобулины, субпопуляции Т- и В-лимфоцитов, продукты метаболизма костной и хрящевой ткани, генетические, метаболические маркеры), позволяющие осуществлять иммунологический мониторинг и прогнозирование эффективности терапии РЗ ингибиторами фактора некроза опухоли α (инфликсимаб, адалимумаб, голимумаб, этанерцепт), анти-В-клеточными препаратами (ритуксимаб, белимумаб), антагонистом рецептора интерлейкина 6 (тоцилизумаб), блокатором костимуляции Т-клеток (абатацепт). Наряду с традиционными униплексными методами иммунодиагностики все шире применяется мультиплексный анализ биомаркеров, основанный на генетических, транскриптомных и протеомных технологиях с использованием ДНК- и белковых микрочипов, полимеразной цепной реакции, проточной цитометрии. Поиск и валидация иммунологических предикторов эффективного ответа на терапию ГИБП создает предпосылки для оптимизации и снижения стоимости лечения этими препаратами

Metabolomic profiles of hepatocellular carcinoma in a European prospective cohort

Background: Hepatocellular carcinoma (HCC), the most prevalent form of liver cancer, is difficult to diagnose and has limited treatment options with a low survival rate. Aside from a few key risk factors, such as hepatitis, high alcohol consumption, smoking, obesity, and diabetes, there is incomplete etiologic understanding of the disease and little progress in identification of early risk biomarkers. Methods: To address these aspects, an untargeted nuclear magnetic resonance metabolomic approach was applied to pre-diagnostic serum samples obtained from first incident, primary HCC cases (n = 114) and matched controls (n = 222) identified from amongst the participants of a large European prospective cohort. Results: A metabolic pattern associated with HCC risk comprised of perturbations in fatty acid oxidation and amino acid, lipid, and carbohydrate metabolism was observed. Sixteen metabolites of either endogenous or exogenous origin were found to be significantly associated with HCC risk. The influence of hepatitis infection and potential liver damage was assessed, and further analyses were made to distinguish patterns of early or later diagnosis. Conclusion: Our results show clear metabolic alterations from early stages of HCC development with application for better etiologic understanding, prevention, and early detection of this increasingly common cancer.This work was supported by the French National Cancer Institute (L’Institut National du Cancer; INCA; grant number 2009-139; PI: M. Jenab). AF received financial support (BDI fellowship) from the Centre National de la Recherche Scientifique (CNRS) and Bruker Biospin. The coordination of EPIC is financially supported by the European Commission (DG-SANCO) and the International Agency for Research on Cancer. The national cohorts are supported by Danish Cancer Society (Denmark); Ligue Contre le Cancer, Institut Gustave Roussy, Mutuelle Générale de l’Education Nationale, and Institut National de la Santé et de la Recherche Médicale (INSERM) (France); Deutsche Krebshilfe, Deutsches Krebsforschungszentrum (DKFZ), and Federal Ministry of Education and Research (Germany); Hellenic Health Foundation (Greece); Italian Association for Research on Cancer (AIRC), National Research Council, Associazione Italiana per la Ricerca sul Cancro-AIRC-Italy, and AIRE-ONLUS Ragusa, AVIS Ragusa, Sicilian Government (Italy); Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), and Statistics Netherlands (the Netherlands); European Research Council (ERC; grant number ERC-2009-AdG 232997) and Nordforsk, and Nordic Center of Excellence Programme on Food, Nutrition and Health (Norway); Health Research Fund (FIS), Regional Governments of Andalucía, Asturias, Basque Country, Murcia (No. 6236) and Navarra, and ISCIII RETIC (RD06/0020) (Spain); Swedish Cancer Society, Swedish Scientific Council, and Regional Government of Skåne and Västerbotten (Sweden); Cancer Research UK, Medical Research Council, Stroke Association, British Heart Foundation, Department of Health, Food Standards Agency, and Wellcome Trust (UK)