Problems and prospects of development of ecological tourism in Ireland

The paper presents the research on the development of ecological tourism in Ireland. The basic directions and problems of development of ecotourism. Income from ecotourism in the country was analyzed in the article, as well as the model for the attraction of tourists to Irelan

The infrastructure of public catering in the context of tourist city space development

To assess the impact of environmental factors on the activities of catering enterprises of the Belgorod region and the quality of customer service, the authors proposed a method using STEP-analysis and SWOT-analysis. The analysis of environmental factors was carried out on the basis of the expert evaluation results conducted in two stage

Sociological diagnostics of crowdsourcing technology in the practice of regional management

The article proposes a methodology for identifying and analyzing the technology of crowdsourcing, examines the main stages of the formation, and analyzes the implementation of crowdsourcing technology into the practice of regional managemen

Molecular epidemiology of serogroup a meningitis in Moscow, 1969 to 1997.

Molecular analysis of 103 serogroup A Neisseria meningitidis strains isolated in Moscow from 1969 to 1997 showed that four independent clonal groupings were responsible for successive waves of meningococcal disease. An epidemic from 1969 to the mid-1970s was caused by genocloud 2 of subgroup III, possibly imported from China. Subsequent endemic disease through the early 1990s was caused by subgroup X and then by subgroup VI, which has also caused endemic disease elsewhere in eastern Europe. A 1996 epidemic was part of the pandemic spread from Asia of genocloud 8 of subgroup III. Recent genocloud 8 epidemic disease in Moscow may represent an early warning for spread of these bacteria to other countries in Europe

Hunting for origins of migraine pain: cluster analysis of spontaneous and capsaicin-induced firing in meningeal trigeminal nerve fibers

International audienceTrigeminal nerves in meninges are implicated in generation of nociceptive firing underlying migraine pain. However, the neurochemical mechanisms of nociceptive firing in meningeal trigeminal nerves are little understood. In this study, using suction electrode recordings from peripheral branches of the trigeminal nerve in isolated rat meninges, we analyzed spontaneous and capsaicin-induced orthodromic spiking activity. In control, biphasic single spikes with variable amplitude and shapes were observed. Application of the transient receptor potential vanilloid 1 (TRPV1) agonist capsaicin to meninges dramatically increased firing whereas the amplitudes and shapes of spikes remained essentially unchanged. This effect was antagonized by the specific TRPV1 antagonist capsazepine. Using the clustering approach, several groups of uniform spikes (clusters) were identified. The clustering approach combined with capsaicin application allowed us to detect and to distinguish "responder" (65%) from "non responder" clusters (35%). Notably, responders fired spikes at frequencies exceeding 10 Hz, high enough to provide postsynaptic temporal summation of excitation at brainstem and spinal cord level. Almost all spikes were suppressed by tetrodotoxin (TTX) suggesting an involvement of the I I X-sensitive sodium channels in nociceptive signaling at the peripheral branches of trigeminal neurons. Our analysis also identified transient (desensitizing) and long-lasting (slowly desensitizing) responses to the continuous application of capsaicin. Thus, the persistent activation of nociceptors in capsaicin-sensitive nerve fibers shown here may be involved in trigeminal pain signaling and plasticity along with the release of migraine-related neuropeptides from TRPV1 positive neurons. Furthermore, cluster analysis could be widely used to characterize the temporal and neurochemical profiles of other pain transducers likely implicated in migraine

О деятельности Комитета по стандартным образцам Международной организации по стандартизации (ИСО/РЕМКО) и проведении 39-го заседания ИСО/РЕМКО в Российской Федерации

The article deals with the results of 39th ISO/REMCO Committee on reference materials meeting (14-16 June 2016, Ekaterinburg, Russian Federation). The meeting was moderated by Federal Agency on Technical Regulating and Metrology (Rosstandart) and Ural Research Institute for Metrology (UNIIM). 37 representatives from 19 countries took part in the meeting (Australia, Belgium, Brazil, Great Britain, Germany, Israel, Kazakhstan, Canada, China, Korea, Netherlands, Russia, USA, Ukraine, France, Czech Republic, Switzerland, Republic of South Africa, Japan) including representatives of national authorities on metrology and national institutes for metrology which cooperate with ISO/REMCO organizations (EDQM, ILAC, CITAC, OIML, UILI) and other ISO technical committees. The meeting dealt with the following issues: final version development of ISO 17034 "General requirements for the competence of reference material producers" (instead of ISO Guide 34-2009) (ISO/CASCO/JWG 43); final version development of ISO Guide 35 "Reference materials - Guidance for characterization and assessment of homogeneity and stability" (instead of ISO Guide 35:2006) (WG 16); particularities of the characterization of pure materials (AHG4); recent advancements in the assessment of homogeneity and stability for reference materials (AHG5); development of the technical report for development of nominal properties reference materials; informational support of ISO/REMCO activities. Finally the resolutions were adopted to accomplish till the next ISO/REMCO meetingВ статье приведены сведения о результатах проведения 39-го заседания Комитета по стандартным образцам Международной организации по стандартизации (14-16 июня 2016 г., г. Екатеринбург, Российская Федерация). Модераторами заседания выступили Госстандарт и ФГУП «УНИИМ». В заседании приняли участие 37 представителей из 19 стран (Австралия, Бельгия, Бразилия, Великобритания, Германия, Израиль, Казахстан, Канада, Китай, Корея, Нидерланды, Россия, США, Украина, Франция, Чешская Республика, Швейцария, ЮАР, Япония), в том числе представители национальных органов по метрологии, национальных метрологических институтов, сотрудничающих с ИСО/РЕМКО организаций (EDQM, ILAC, CITAC, OIML, UILI), других технических комитетов ИСО. На заседании состоялось обсуждение вопросов о разработке окончательной редакции ISO 17034 «Общие требования к компетентности изготовителей стандартных образцов» (взамен ISO Guide 34-2009) (ISO/CASCO/JWG 43); о разработке окончательной редакции ISO Guide 35 «Стандартные образцы. Руководство по характеризации, оцениванию однородности и стабильности стандартных образцов» (взамен ISO Guide 35:2006) (WG 16); об особенностях характеризации стандартных образцов (СО) чистых веществ (AHG4); о последних достижениях в области исследования однородности и стабильности стандартных образцов (AHG5); о разработке технического отчета по разработке СО номинальных свойств; об информационном обеспечении деятельности ИСО/ РЕМКО. По результатам приняты резолюции для их выполнения до следующего заседания ИСО/РЕМКО

Changes in DNA methylation profile in liver tissue during progression of HCV-induced fibrosis to hepatocellular carcinoma

In this study we compared methylation levels of 27,578 CpG sites between paired samples of the tumor and surrounding liver tissues with various degrees of damage (fibrosis, cirrhosis) in HCV-induced hepatocellular carcinoma (HCC) patients, as well as between tumor and normal tissue in non-viral HCC patients, using GSE73003 and GSE37988 data from GEODataSets (https://www.ncbi.nlm.nih.gov/). A significantly lower number of differentially methylated sites (DMS) were found between HCC of non-viral etiology and normal liver tissue, as well as between HCC and fibrosis (32 and 40), than between HCC and cirrhosis (2450 and 2304, respectively, according to GSE73003 and GSE37988 datasets). As the pathological changes in the tissue surrounding the tumor progress, the ratio of hyper-/ hypomethylated DMSs in the tumor decreases. Thus, in tumor tissues compared with normal/fibrosis/cirrhosis of the liver, 75/62.5/47.7 % (GSE73003) and 16 % (GSE37988) of CpG sites are hypermethylated, respectively. Persistent hypermethylation of the ZNF154 and ZNF540 genes, as well as CCL20 hypomethylation, were registered in tumor tissue in relation to both liver fibrosis and liver cirrhosis. Protein products of the EDG4, CCL20, GPR109A, and GRM8 genes, whose CpG sites are characterized by changes in DNA methylation level in tumor tissue in the setting of cirrhosis and fibrosis, belong to “Signaling by G-protein-coupled receptors (GPCRs)” category. However, changes in the methylation level of the “driver” genes for oncopathology (АРС, CDKN2B, GSTP1, ELF4, TERT, WT1) are registered in tumor tissue in the setting of liver cirrhosis but not fibrosis. Among the genes hypermethylated in tumor tissue in the setting of liver cirrhosis, the most represented biological pathways are developmental processes, cell-cell signaling, transcription regulation, Wnt-protein binding. Genes hypomethylated in liver tumor tissue in the setting of liver cirrhosis are related to olfactory signal transduction, neuroactive ligand-receptor interaction, keratinization, immune response, inhibition of serine proteases, and zinc metabolism. The genes hypermethylated in the tumor are located at the 7p15.2 locus in the HOXA cluster region, and the hypomethylated CpG sites occupy extended regions of the genome in the gene clusters of olfactory receptors (11p15.4), keratin and keratin-associated proteins (12q13.13, 17q21.2, and 21q22.11), epidermal differentiation complex (1q21.3), and immune system function loci 9p21.3 (IFNA, IFNB1, IFNW1 cluster) and 19q13.41–19q13.42 (KLK, SIGLEC, LILR, KIR clusters). Among the genes of fibrogenesis or DNA repair, cg14143055 (ADAMDEC1) is located in the binding region of the HOX gene family transcription factors (TFs), while cg05921699 (CD79A), cg06196379 (TREM1) and cg10990993 (MLH1) are located in the binding region of the ZNF protein family transcription factor (TF). Thus, the DNA methylation profile in the liver in HCV-induced HCC is unique and differs depending on the degree of surrounding tissue lesion – liver fibrosis or liver cirrhosis

ФАРМАКОЭКОНОМИКА КАК НОВЫЙ ИНСТРУМЕНТ ФАРМАЦЕВТИЧЕСКОГО МАРКЕТИНГА

A properly conducted pharmacoeconomic study and its results are a new element in the body of evidence for drugs recently introduced into clinical practice. Utilization of pharmacoeconomic analysis results as a new instrument in pharmaceutical marketing lets marketing specialists know what information to convey to health care decision makers and how to bring this information full, correct, and easy to understand.Хорошо проведенное фармакоэкономическое исследование и полученные в ходе него результаты представляют новый элемент доказательной базы по лекарственным средствам (ЛС) недавно введенным в клиническую практику. Использование результатов фармакоэкономического анализа в качестве нового инструмента в фармацевтическом маркетинге позволяет дать ответ специалистам в области маркетинга «что» нужно сообщать лицам, принимающим решения в системе здравоохранения и «как» донести эту информацию в полном и неискаженном виде, говоряс ними на одном языке