System of monitoring of Internet resources as instrument of digital marketing

The concept of digital marketing as targeted and interactive marketing of goods and services which is directed to improve the operating mechanism of sales of products through the application of different digital technologies has been considered. Working process with information, necessary for improvement of content of the website and optimization of sales propositions has been shown. The main indicators of web analytics, including its analytical cycle have been considered in detail. The fundamental objectives, tools and services of web analytics, allowing to organize effectively its work, have been determined

БЕЗОПАСНОСТЬ ДЛИТЕЛЬНОЙ ТЕРАПИИ ВАРФАРИНОМ: ЧАСТОТА КРОВОТЕЧЕНИЙ И КЛИНИЧЕСКИЕ ПРЕДИКТОРЫ ИХ РАЗВИТИЯ (результаты проспективного 15-летнего наблюдения)

Despite the long-term clinical experience, bleeding remains the greatest danger for patients taking vitamin K antagonists. Moreover, even the presence of risk factors for hemorrhagic complications in a patient should not be the only reason for cancelling anticoagulant therapy. The challenge in assessing the frequency of hemorrhage is primarily explained by different approaches to hemorrhage classification. For patients receiving long-term anticoagulant therapy, along with fatal and life threatening hemorrhages, minor and clinically significant small hemorrhages should be taken into account to assess the safety of treatment. The 15-year prospective follow-up of patients receiving warfarin found that the frequency of all hemorrhagic complications was 8.66/100 patient-years, major hemorrhage — 2.98/100 patient-years, and clinically significant hemorrhage — 2.62/100 patient-years. According to the results of the discriminant analysis, the predictors for the development of major and clinically significant hemorrhagic complications in patients receiving long-term therapy with warfarin are administration of proton pump inhibitors, labile INR during therapy, recurrent minor hemorrhage in history and amiodarone therapy. The 15-year prospective follow-up of patients receiving warfarin demonstrated that minor hemorrhagic complications account for one third of all bleedings and are not associated with the subsequent development of clinically significant and major bleeding in patients. The prospective follow-up also found an increase in the frequency of hemorrhagic complications if one or two antiplatelet agents were added to warfarin therapy. The incidence of major and minor clinically significant hemorrhagic complications during triple antithrombotic therapy was 24/100 patient-years, which was higher than in the warfarin monotherapy subgroups and in the case of combining warfarin with an antiaggregant (4.4 and 8.47%, respectively). The localization of bleeding was analyzed to reveal that in triple antithrombotic therapy the greatest number of bleedings occurred in the upper or lower gastrointestinal tract. The relative risk was calculated to confirm that triple antithrombotic therapy significantly increased the risk of gastrointestinal bleeding by 3.02 times.  Несмотря на длительный клинический опыт, кровотечения у больных, принимающих антагонисты витамина К, по-прежнему остаются основной опасностью терапии. При этом даже наличие у больного факторов риска геморрагических осложнений не должно являться единственным основанием для отказа от анти-коагулянтной терапии. Сложность оценки частоты кровотечений обусловлена в первую очередь различными подходами к их классификации. Для больных, находящихся на длительной антикоагулянтной терапии, для оценки безопасности лечения наряду с фатальными и жизнеугрожающими важен учет малых и клинически значимых небольших геморрагий. На основании 15-летнего проспективного наблюдения за больными, получающими терапию варфарином, выявлено, что частота всех геморрагических осложнений составила 8,66/100 пациенто-лет, больших кровотечений — 2,98/100 пациенто-лет, а клинически значимых — 2,62/100 пациенто-лет. По результатам дискриминантного анализа предикторами развития больших и клинически значимых геморрагических осложнений у больных, длительно принимающих варфарин, являются прием ингибиторов протонного насоса, лабильное МНО на протяжении терапии, рецидивирующие малые геморрагии в анамнезе и терапия амиодароном. На основании 15-летнего проспективного наблюдения за больными, получающими терапию варфарином, выявлено, что малые геморрагические осложнения составляют треть от всех кровотечений и не связаны с последующим развитием у больных клинически значимых и больших кровотечений. На основании проспективного наблюдения выявлено увеличение частоты геморрагических осложнений при добавлении одного и двух антиагрегантов к терапии варфарином. Частота больших и небольших клинически значимых геморрагических осложнений при тройной антитромботической терапии составила 24/100-пациенто-лет, что было выше, чем в подгруппах монотерапии варфарином и при сочетании варфарина с одним антиагрегантом (4,4 и 8,47% соответственно). Анализ локализации кровотечений выявил, что при тройной антитромботической терапии наибольшее число кровотечений произошло из верхних или нижних отделов желудочно-кишечного тракта. Проведенный расчет относительного риска подтвердил, что тройная антитромботическая терапия достоверно повышала риск развития желудочно-кишечных кровотечений в 3,02 раза. 

Russian Science Foundation grant No. 20-14-00140 supported this study. The authors are thankful to the multi-access Center “Bioinformatics” for the use of computational resources as supported by Russian government project FWNR-2022-0020 and the Russian Federal Science and Technology Program for the Development of Genetic Technologies.

It is generally accepted that during the domestication of food plants, selection was focused on their productivity, the ease of their technological processing into food, and resistance to pathogens and environmental stressors. Besides, the palatability of plant foods and their health benefits could also be subjected to selection by humans in the past. Nonetheless, it is unclear whether in antiquity, aside from positive selection for beneficial properties of plants, humans simultaneously selected against such detrimental properties as allergenicity. This topic is becoming increasingly relevant as the allergization of the population grows, being a major challenge for modern medicine. That is why intensive research by breeders is already underway for creating hypoallergenic forms of food plants. Accordingly, in this paper, albumin, globulin, and β­amylase of common wheat Triticum aestivum L. (1753) are analyzed, which have been identified earlier as targets for attacks by human class E immunoglobulins. At the genomic level, we wanted to find signs of past negative selection against the allergenicity of these three proteins (albumin, globulin, and β­amylase) during the domestication of ancestral forms of modern food plants. We focused the search on the TATA­binding protein (TBP)­binding site because it is located within a narrow region (between positions –70 and –20 relative to the corresponding transcription start sites), is the most conserved, necessary for primary transcription initiation, and is the best­studied regulatory genomic signal in eukaryotes. Our previous studies presented our publicly available Web service Plant_SNP_TATA_Z­tester, which makes it possible to estimate the equilibrium dissociation constant (KD) of TBP complexes with plant proximal promoters (as output data) using 90 bp of their DNA sequences (as input data). In this work, by means of this bioinformatics tool, 363 gene promoter DNA sequences representing 43 plant species were analyzed. It was found that compared with non­food plants, food plants are characterized by significantly weaker affinity of TBP for proximal promoters of their genes homologous to the genes of commonwheat globulin, albumin, and β­amylase (food allergens) (p< 0.01, Fisher’s Z­test). This evidence suggests that in the past humans carried out selective breeding to reduce the expression of food plant genes encoding these allergenic proteins