New angiogenic regulators produced by TAMs: perspective for targeting tumor angiogenesis

Angiogenesis is crucial to the supply of a growing tumor with nutrition and oxygen. Inhibition of angiogenesis is one of the main treatment strategies for colorectal, lung, breast, renal, and other solid cancers. However, currently applied drugs that target VEGF or receptor tyrosine kinases have limited efficiency, which raises a question concerning the mechanism of patient resistance to the already developed drugs. Tumor-associated macrophages (TAMs) were identified in the animal tumor models as a key inducer of the angiogenic switch. TAMs represent a potent source not only for VEGF, but also for a number of other pro-angiogenic factors. Our review provides information about the activity of secreted regulators of angiogenesis produced by TAMs. They include members of SEMA and S100A families, chitinase-like proteins, osteopontin, and SPARC. The COX-2, Tie2, and other factors that control the pro-angiogenic activity of TAMs are also discussed. We highlight how these recent findings explain the limitations in the efficiency of current anti-angiogenic therapy. Additionally, we describe genetic and posttranscriptional mechanisms that control the expression of factors regulating angiogenesis. Finally, we present prospects for the complex targeting of the pro-angiogenic activity of TAMs

PFKFB3 overexpression in monocytes of patients with colon but not rectal cancer programs pro-tumor macrophages and is indicative for higher risk of tumor relapse

Introduction: Circulating monocytes are main source for tumor-associated macrophages (TAMs) that control tumor growth, angiogenesis, metastasis and therapy resistance. We raised the questions how monocyte programming is affected by growing tumors localized in colon and rectal sections, and how treatment onsets affect monocyte programming in the circulation. Methods: Patients with rectal cancer and colon cancer were enrolled in the study. Peripheral blood monocytes were characterized by phenotypic analysis using flow cytometry, by transcriptomic analysis using RNA sequencing and by gene expression analysis using real-time RT-PCR. Phenotypic analysis was performed with IF/confocal microscopy. Spatial transcriptomic analysis was applied using GeoMX DSP-NGS. Results: In patients with rectal cancer, increased amount of CCR2+ monocytes was indicative for the absence of both lymphatic and hematogenous metastasis. In contrast, in patients with colon cancer CD163+ monocytes were indicative for LN metastasis. NGS analysis identified tumor-specific transcriptional programming of monocytes in all CRC patients compared to healthy individuals. The key transcriptional difference between monocytes of patients with colon and rectal cancer was increased expression of PFKFB3, activator of glycolysis that is currently considered as therapy target for major solid cancers. PFKFB3-expressing monocyte-derived macrophages massively infiltrated tumor in colon. Nanostring technology identified correlation of PFKFB3 with amount and tumor-promoting properties of TAMs in colon but not in rectal cancer. PFKFB3 was indicative for tumor relapse specifically in colon cancer. Discussion: Our findings provide essential argument towards CRC definition to cover two clinically distinct cancers – colon cancer and rectal cancer, that differentially interact with innate immunity

Сравнение подходов к реализации образовательных программ по направлению "бизнес-информатика" в России и Германии

Business informatics is a relatively young academic discipline. During the last years several efforts have been made to compare the German discipline Wirtschaftsinformatik with the Anglo-American sister discipline information systems. However, these studies have mainly focused on research activities; they have not attempted to compare curricula in both disciplines. With the change of the political and economic system in the former Soviet Union and the introduction of courses of studies in business informatics in Russia it may be helpful to compare the German with the Russian approach to teaching business informatics. The objective of this paper is to compare bachelor studies in business informatics at selected universities in Russia and Germany. This paper contains the outline of the history of business informatics as a scientific discipline in Russia and Germany, a description of professional organizations, standards, and guidelines relevant for business informatics in both countries. Special attention is given to an overview of students studying business informatics, a description of time scales and grading scales and the structure of teaching plans in Russia and Germany. The paper contains the explanation of the method used to analyze and compare bachelor studies at ten German and ten Russian universities. Findings of the analysis concern details of bachelor studies in business informatics at German and Russian universities and highlight similarities and differences

Isolation and genetic analysis of the chikungunya virus from Aedes aegypti and Aedes albopictus mosquitoes captured in Central America

Introduction. The habitat of mosquitoes belonging to the genera Aedes spp., Culex spp., Culiseta spp. is in South and Central America, including Nicaragua. Monitoring of the spread of mosquito vectors and assessment of the infection with arboviruses can provide information on possible occurrence of new diseases or an increase in the reported cases, changes in the infectivity of viruses for humans due to changes in pathogen transmitters. The purpose of this study was isolation and identification of arboviruses belonging to the Flavivirus and Alphavirus genera from A. albopictus, A. aegypti, Culiseta spp., Culex spp. mosquitoes captured in forests of Nicaragua. Materials and methods. A. albopictus, A. aegypti, Culiseta spp., Culex spp. mosquitoes were captured during the dry season in 2021 in forested areas of Nicaragua in four different locations. Mosquitoes were sorted into pools, each containing 5-8 mosquitoes (236 pools in total). Using the reverse transcription polymerase chain reaction, the pools were tested for the presence of chikungunya (CHIKV), dengue, Zika, and yellow fever viruses. Positive pools were inoculated into the C6/36 cell culture to obtain isolates and for their further sequencing. Results. The dengue virus was detected only in Aedes spp. mosquitoes: in 7 pools — A. aegypti, in 1 — A. albopictus. CHIKV was also detected only in Aedes spp. mosquitoes: in 3 pools — A. aegypti, in 1 — A. albopictus. The sequencing of nucleotide sequences of 6К, Е1, Е2, and NS1 genes of CHIKV isolated from A. albopictus mosquitoes showed that compared to the similar gene sequences from CHIKV isolates recovered from A. aegypti mosquitoes, the 6K gene region contained 4 nucleotide and 4 amino acid substitutions, while the E1 region contained 16 nucleotide substitutions, 10 of them led to amino acid substitutions; the E2 region contained 14 nucleotide and 11 amino acid substitutions; the NS1 region contained 33 nucleotide and 19 amino acid substitutions

Первичный серологический статус и иммунологическая эффективность вакцинации против Streptococcus pneumoniae и Haemophilus influenzae типа b у детей с бронхолегочной дисплазией: когортное исследование

Background. The primary serological status of children with bronchopulmonary dysplasia (BPD) with respect to respiratory significant pathogens remains unstudied. Wherein, the efficacy of vaccination of children with BPD against Streptococcus pneumoniae and Haemophilus influenzae type b (Hib) has been studied in a small number of studies which results are contradictory.Objective. Our aim was to study the pre-vaccinal serological status with regard to S. pneumoniae and Hib and the immunological efficacy of vaccination against these infections in children with BPD.Methods. The study included children with BPD without exacerbation. The immunological efficacy of conjugate vaccines — pneumococcal 13-valent and against Haemophilus influenza type b — was assessed by the level of IgG against S. pneumoniae and Hib using the ELISA method. The level of antibodies was determined before vaccination and 1 or 3–6 months afterwards.Results. The study included 32 children with BPD, mean age at the time of determining primary serological status was 13.3±1.3 months, at the time of vaccination — 15.2±1.5 months. The mean gestational age was 28.7±0.8 weeks, the body weight at birth was 1225±180 g. Before vaccination, all children with BPD had no protective antibody titre against S. pneumoniae and Hib averaging 0.2±0.034 and 0.13±0.0106 mg/L, respectively. One month after vaccination, the level of antibodies to S. pneumoniae reached 12.9±2.34 mg/L to Hib — 3.34±0.769 mg/L.Conclusion. After immunization with a pneumococcal 13-valent conjugate vaccine and a conjugate vaccine against Haemophilus influenzae type b, the concentration of IgG against S. pneumoniae exceeded the protective level in all examined patients (100%), the concentration to Hib — in 29 (90.6%).Обоснование. Первичный серологический статус детей с бронхолегочной дисплазией (БЛД) в отношении респираторно значимых патогенов остается неизученным. При этом эффективность вакцинации детей с БЛД против Streptococcus pneumoniae и Haemophilus influenzae типа b (Hib) изучалась в небольшом числе исследований, результаты которых противоречивы. Цель исследования — изучить довакцинальный серологический статус в отношении S. pneumoniae и Hib и иммунологическую эффективность вакцинации против этих инфекций у детей с БЛД.Методы. В исследование включали детей с БЛД, вне обострения. Иммунологическую эффективность конъюгированных вакцин — 13-валентной пневмококковой и против гемофильной инфекции типа b — оценивали по уровню IgG к S. pneumoniae и Hib методом ELISA. Уровень антител определяли до вакцинации и спустя 1 и 3–6 мес.Результаты. Включено 32 ребенка с БЛД средний возраст которых на момент определения первичного серологического статуса составил 13,3±1,3 мес, на момент вакцинации — 15,2±1,5 мес. Средний гестационный возраст — 28,7±0,8 нед, масса тела при рождении — 1225±180 г. У всех детей с БЛД до вакцинации отсутствовал защитный титр антител к S. pneumoniae и Hib, составив в среднем 0,2±0,034 и 0,13±0,0106 мг/л соответственно. Через 1 мес после вакцинации уровень антител к S. pneumoniae достигал 12,9±2,34 мг/л, к Hib — 3,34±0,769 мг/л.Заключение. После иммунизации 13-валентной пневмококковой конъюгированной вакциной и конъюгированной вакциной против гемофильной инфекции типа b концентрация IgG к S. pneumoniae превышала защитный уровень у всех обследованных пациентов (100%), концентрация к Hib — у 29 (90,6%).Конфликт интересовЛ.С. Намазова-Баранова — получение исследовательских грантов от фармацевтических компаний Пьер Фабр, Genzyme Europe B.V., ООО «Астра зенека Фармасьютикалз», Gilead / PRA «Фармасьютикал Рисерч Ассошиэйтс СиАйЭс», Teva Branded Pharma ceuti cal products R&D, Inc. / ООО «ППД Девелопмент (Смоленск)», «Сталлержен С.А.» / «Квинтайлс ГезмбХ» (Австрия). М.В. Федосеенко — получение гонораров от компании Sanofi, Pfizer за чтение лекций

WSES guidelines for management of Clostridium difficile infection in surgical patients

In the last two decades there have been dramatic changes in the epidemiology of Clostridium difficile infection (CDI), with increases in incidence and severity of disease in many countries worldwide. The incidence of CDI has also increased in surgical patients. Optimization of management of C difficile, has therefore become increasingly urgent. An international multidisciplinary panel of experts prepared evidenced-based World Society of Emergency Surgery (WSES) guidelines for management of CDI in surgical patients.Peer reviewe

Сравнительный анализ эмоционального здоровья первоклассников при разных стилях семейного воспитания

Introduction. Parenting styles have a considerable impact on the emotional health of children. This study aims to identify the characteristics of emotional health among first-grade children raised with different parenting styles. Methods. The study used the following psychological assessment tools: (a) the Sixteen Personality Factor Questionnaire, 16PF, developed by R. Cattell (junior version); (b) the test for Diagnostics of the Level of Empathic Abilities by V. V. Boyko; (c) the School Anxiety Scale, SAS, developed B. Phillips; (d) Buss–Durkee Hostility Inventory; and (e) the Emotional Faces test developed by N. Ya. Semago. To assess parenting styles, we used the Parental Attitude Research Instrument, PARI (E. S. Schaefer, R. K. Bell) and the Analysis of Family Relationships questionnaire, AFR (E. G. Eidemiller, V. V. Yustitskis). A total of 283 children aged 7–8 years from the schools of Arkhangelsk city (123 girls and 160 boys) participated in the study. Statistical analysis was performed using descriptive statistics, maximum likelihood factor analysis with varimax normalized rotation, and parametric ANOVA. Results and Discussion. Emotional awareness, aggression, anxiety, and empathy were the most significant characteristics of emotional health for all the first-grade students. Indulgent hyperprotaction was associated with a high level of school anxiety; disturbance in family role attitudes correlated with difficulties in the ability to recognize and understand emotions; attachment trauma was associated with a high level of aggression and a low level of empathy. Therefore, unfavorable parenting styles may cause emotional health disorders in children and lead to an increase in the levels of anxiety and aggression, difficulties in recognizing and understanding emotions, and a low level of empathy. Negative parenting styles are a predictor of emotional health disorders in children, which requires timely prevention.Введение. Впервые с учетом системного, комплексного подхода к описанию эмоционального здоровья первоклассника нами было выдвинуто и доказано предположение о роли стиля семейного воспитания в становлении и формировании различных аспектов изучаемого феномена детей 7–8 лет. Методы. В работе использовались методики: многофакторного исследования личности (Р. Кеттелл; детский вариант), «Диагностика уровня эмпатических способностей» (В. В. Бойко), тест уровня школьной тревожности (Б. Н. Филлипс), «Диагностика агрессивности детей» (А. Басс, А. Дарки), «Эмоциональные лица» (Н. Я. Семаго). Стили семейного воспитания определяли с помощью методик изучения родительских установок (РARI) (Е. С. Шефер, Р. К. Белл) и опросника «Анализ семейных взаимоотношений (АСВ)» (Э. Г. Эйдемиллер, В. В. Юстицкис). Обследовано 283 ребенка в возрасте 7–8 лет школ г. Архангельска (123 девочки и 160 мальчиков). Статистический анализ проводился с использованием методов описательных статистик, факторного анализа методом максимального правдоподобия с применением варимаксимального нормализованного вращения, параметрического критерия ANOVA. Результаты и их обсуждение. Обнаружено, что для всех обследованных первоклассников наиболее значимыми являются такие характеристики эмоционального здоровья, как осмысленность эмоций, агрессивность, тревожность, эмпатия. При стиле семейного воспитания «потворствующая гиперпротекция» наблюдается достоверно высокий уровень школьной тревожности ребенка, при «нарушении ролевых установок в семье» отмечаются трудности с опознаванием и осмысленностью эмоций у школьника, при «нарушении эмоционального контакта ребенка с родителями» выявлены высокая агрессивность и низкая эмпатия у первоклассников. Обсуждается, что неблагоприятные стили семейного воспитания могут быть причиной нарушения эмоционального здоровья ребенка: повышения уровня тревожности, агрессивности, появления трудностей с опознаванием и осмысленностью эмоций, низкого уровня эмпатии. Негативные стили семейного воспитания являются предиктом нарушений эмоционального здоровья детей, что требует своевременной профилактики и коррекции