Pharmacoeconomic study of the effectiveness of cytogenetic studies in patients with MM before prescribing first-line therapy

Purpose of the study. Conducting an assessment of the economic consequences (clinical and economic analysis) when conducting cytogenetic studies before prescribing various first-line treatment regimens for multiple myeloma (MM). Materialsand methods. The pharmacoeconomic study was carried out using the method of cost analysis, “cost-effectiveness” within the framework of the State Guarantee Program (SGP). Results. A review of the literature demonstrated that a limited number of data are currently available on the clinical effectiveness of the analyzed regimens in the first line, both in patients with normal and high cytogenetic risk. The cost-effectiveness analysis showed that among the three studied 1st-line treatment regimens (VMP, Rd, VRd), in terms of PFS (progression-free survival), the coefficient was minimal for the VMP regimen in patients with high cytogenetic risk. Conclusion. The study showed that the choice and prescription of first-line therapy, depending on the results of a cytogenetic study, is a clinically effective and cost-effective approach to organizing medical care for adult patients with multiple myeloma in the Russian Federation. This could be used in the future to formulate

The Yongbyon Reactor as an Object af The Six-Party Talks an the DPRK’s Nuclear Program (Based on the Materials of the American Press)

The article was submitted on 28.03.2020.В статье проводится анализ событий шестисторонних переговоров по ядерной программе Северной Кореи, касающихся проблемы функционирования реактора в Йонбёне, через призму американских СМИ. Актуальность темы обусловлена тем, что именно Йонбёнский научно-исследовательский центр стал первым ядерным комплексом в КНДР, который позволил Северной Корее производить оружейный плутоний, что широко обсуждалось в средствах массовой информации США. Реализация ядерной программы оказала большое влияние на американо-северокорейские отношения, в которых Соединенные Штаты стремились контролировать действия КНДР в этой сфере. Для решения проблемы использования ядерного центра в Йонбёне в 2003–2009 гг. была организована серия Шестисторонних переговоров при участии США, КНР, России, Японии, Республики Корея и КНДР. Так как этот вопрос был непосредственно связан с Соединенными Штатами и их внешней политикой, он широко освещался в американских СМИ, главным образом в «Нью-Йорк таймс» и «Лос-Анджелес таймс», материалы которых послужили основным источником в написании данной статьи. Если в «Нью-Йорк таймс» чаще всего публиковались резолюции, итоги официальных встреч, цитировались тексты официальных документов, то в «Лос-Анджелес таймс» шестисторонние переговоры освещались лишь фрагментарно. В данной статье также использовались материалы местных газет, таких как «Остин америкэн стейтмент» и «Ньюс Джорнал», которые, в силу своей локальной специфики, освещали лишь наиболее важные события. Отметим, что практически во всех исследуемых изданиях освещалась не только точка зрения США, но и других стран-участниц шестисторонних переговоров. Большая часть публикаций отражала официальное мнение правительства Соединенных Штатов, подвергая критике позицию КНДР, однако редакция ряда газет выражала свое несогласие с жесткой позицией США по отношению к ядерной программе Северной Кореи. В статье рассматривается и анализируется позиция американской прессы в отношении данной проблемы, делаются обоснованные выводы.The article analyses events of the Six-Party Talks on North Korea’s nuclear program concerning the problem of the Yongbyon reactor functioning through the prism of the US press. The relevance of the topic is due to the fact that the Yongbyon research center became the first nuclear complex in the DPRK which allowed North Korea to produce weapons-grade plutonium that was widely discussed in the US media. The implementation of the nuclear program had a great impact on US-North Korean relations, with the United States seeking to control the actions of the DPRK in this area. To solve the problem of using the Yongbyon nuclear center, a series of the Six–Party Talks were conducted in the period of 2003–2009 with the participation of the United States, China, Russia, Japan, the Republic of Korea and the North Korean. Since this issue was directly related to the United States and its foreign policy, it was widely covered in the American media, mainly in «The New York Times» and the «Los Angeles Times», whose materials served as a main source for this article. «The New York Times» mostly published resolutions, the results of official meetings, quoted the texts of official documents. In the meantime, the «Los Angeles Times» covered the six-party talks only incompletely and partially. This article also used material of local newspapers, such as the «Austin American-Statesman », the «News Journal» which due to their local specificity covered only the most important events. It should be noted that almost all the publications under study covered not only the point of view of the United States, but also the one of the other countries participating in the Six-Party Talks. Most of the publications reflected an official opinion of the United States government criticizing the position of the DPRK`s administration. In the meanwhile, the editors of a number of newspapers expressed their disagreement with the tough position of the United States concerning North Korea’s nuclear program. The article examines and analyzes the position of the US press in relation to this problem, and reasonable conclusions are made

Defending the genome from the enemy within:mechanisms of retrotransposon suppression in the mouse germline

The viability of any species requires that the genome is kept stable as it is transmitted from generation to generation by the germ cells. One of the challenges to transgenerational genome stability is the potential mutagenic activity of transposable genetic elements, particularly retrotransposons. There are many different types of retrotransposon in mammalian genomes, and these target different points in germline development to amplify and integrate into new genomic locations. Germ cells, and their pluripotent developmental precursors, have evolved a variety of genome defence mechanisms that suppress retrotransposon activity and maintain genome stability across the generations. Here, we review recent advances in understanding how retrotransposon activity is suppressed in the mammalian germline, how genes involved in germline genome defence mechanisms are regulated, and the consequences of mutating these genome defence genes for the developing germline

Alkylresorcinols as New Modulators of the Metabolic Activity of the Gut Microbiota

Alkylresorcinols (ARs) are polyphenolic compounds with a wide spectrum of biological activities and are potentially involved in the regulation of host metabolism. The present study aims to establish whether ARs can be produced by the human gut microbiota and to evaluate alterations in content in stool samples as well as metabolic activity of the gut microbiota of C57BL, db/db, and LDLR (−/−) mice according to diet specifications and olivetol (5-n-pentylresorcinol) supplementation to estimate the regulatory potential of ARs. Gas chromatography with mass spectrometric detection was used to quantitatively analyse AR levels in mouse stool samples; faecal microbiota transplantation (FMT) from human donors to germ-free mice was performed to determine whether the intestinal microbiota could produce AR molecules; metagenome sequencing analysis of the mouse gut microbiota followed by reconstruction of its metabolic activity was performed to investigate olivetol’s regulatory potential. A significant increase in the amounts of individual members of AR homologues in stool samples was revealed 14 days after FMT. Supplementation of 5-n-Pentylresorcinol to a regular diet influences the amounts of several ARs in the stool of C57BL/6 and LDLR (−/−) but not db/db mice, and caused a significant change in the predicted metabolic activity of the intestinal microbiota of C57BL/6 and LDLR (−/−) but not db/db mice. For the first time, we have shown that several ARs can be produced by the intestinal microbiota. Taking into account the dependence of AR levels in the gut on olivetol supplementation and microbiota metabolic activity, AR can be assumed to be potential quorum-sensing molecules, which also influence gut microbiota composition and host metabolism

Alkylresorcinols as a New Type of Gut Microbiota Regulators Influencing Immune Therapy Efficiency in Lung Cancer Treatment

Background. Alkylresorcinols (ARs) are polyphenolic compounds of microbial origin with a wide spectrum of biological activities and are potentially involved in host immune functioning. The present study is aimed at evaluating alterations in AR content in blood serum and faeces from healthy donors and patients with lung cancer in connection with response to immune checkpoint inhibitor (ICI) therapy to estimate the regulatory potential of AR. Methods. Quantitative analysis of AR levels, as well as other microbial metabolites in blood serum and faeces, was performed using gas chromatography with mass spectrometric detection; estimation of lymphocyte subsets was performed by flow cytometry; faecal microbiota transplantation (FMT) from lung cancer patients after ICI therapy to germ-free mice was performed to explore whether the intestinal microbiota could produce AR molecules. Results. AR concentrations in both faeces and serum differ dramatically between healthy and lung cancer donors. The significant increase in AR concentrations in mouse faeces after FMT points to the microbial origin of ARs. For several ARs, there were strong positive and negative correlations in both faeces and serum with immune cells and these interrelationships differed between the therapy-responsive and nonresponsive groups. Conclusions. The content of ARs may influence the response to ICI therapy in lung cancer patients. ARs may be considered regulatory molecules that determine the functioning of antitumor immunity