Does the wall thickness of the left atrial appendage and its isthmus depend on their macroscopic characteristics?

Knowledge in interrelations between gross anatomy of the left atrial appendage (LAA) and thickness of the walls of LAA and periauricular area enables decreasing operational risks in LAA ostium occluding and «Cox-Maze» surgery for atrial fibrillation. The aim of the study was to identify significant interrelations between the macroscopic characteristics of the LAA (size, shape, number of lobes) and the parameters of the wall thickness of the LAA and its isthmus. Material and methods. The study includes 50 heart specimens of patients died from non-cardiac diseases. We examined 60 anatomical sections from 30 hearts by means Olympus SZX2-ZB10 microscope, and histological slices from 20 hearts. Results. The layers of the LAA wall were thinner than those in the isthmus. The thickness of LAA walls did not show direct correlation with the external dimensions of LAA. We found inverse correlation (Rs = – 0.4, p < 0,05) between the thickness of the myocardium, endocardium and some external sizes of LAA. The wall thickness of «chicken wing», «cauliflower» and «arrowhead» was the same. The wall of single-lobe LAA was thinner than that of two-lobed LAA (p = 0.036). The LAA isthmus wall was thinner (p = 0.03) in hearts with «cauliflower» LAA compared to hearts with LAA resembled a «chicken wing». Differences in wall thickness in LAA of various shapes were due to the degree of subepicardial fatty tissue development. Intracardiac operations should be done with the utmost care in patients with «cauliflower» LAA and single-lobe LAA to avoid damage of the LAA and periauricular area. Conclusions. The research found clinically significant interrelations between the LAA wall thickness and the number of its lobes as well as between the LAA isthmus wall thickness and LAA shape variants

Analysis of vitamin D availability of premature infants in the south of Russia

Introduction. Inadequate vitamin D supply worldwide is a public health problem. Low vitamin D levels during pregnancy can lead to abnormal placentation, placental insufficiency and abnormal fetal development, which contributes to poor health after birth.Objective of the study is to analyze the vitamin D status of premature infants born in the south of Russia.Materials and methods. A total of 141 premature infants were examined. Extremely low birth weight was found in 19 (13.4%) newborns, very low birth weight in 35 (24.8%), and low birth weight in 75 (53.2%).Results and discussion. Premature infants had vitamin D deficiency in the majority of cases (51%), with a median of 16.9 [11.7; 22.9] ng/mL. Correlation analysis demonstrated a positive association between 25(OH)D levels and body weight in very low birth weight infants (r = 0.34, p = 0.043). Serum vitamin D concentrations were 1.6 times lower in infants whose mothers did not receive multivitamins than in those whose mothers received multivitamins, 13.8 [9.7; 20.9] and 21.6 [16.9; 28.6] ng/mL, respectively (p = 0.001). Infants with an Apgar score of 7-10 had higher vitamin D levels, 17.8 [11.9; 22.7] ng/mL, than infants with severe asphyxia, 13.8 [9.9; 16.8] ng/mL (p = 0.036). Premature infants with congenital infection had lower 25(OH)D levels than infants without an infectious process, 15.6 [10.8; 22.9] and 18.4 [14.2; 22.7] ng/mL, respectively. Children with an infectious process that subsequently ended in death had lower 25(OH)D levels than children without an infectious process (p = 0.001). Children with cerebral ischemia had lower 25(OH)D concentrations than children without cerebral ischemia (p = 0.001).Conclusions. Premature infants born in the south of Russia have vitamin D deficiency in more than half of the cases. Administration of preparations containing cholecalciferol reduces the proportion of newborns with severe vitamin D deficiency, but does not ensure optimal serum levels. Initially low levels of 25(OH)D can be considered as an unfavorable prognostic sign against the background of the development of congenital infection

Эталонная версия ГРНТИ 2022 г. (Часть 1. Развитие тематической и структурной организации рубрикационных вершин)

The authors  introduce  the  findings  of their  research  on  updating  and improving  the  existing  master  version  of the  State  Rubricator  of Sci-tech  Information  (GRNTI) version 2021 and building  the  General Classification  Schedule  of the  master  GRNTI 2022 version. They define  the  main functions  of GRNTI as the standard classification  of the State System of Sci-tech Information. The functional efficiency  depends on the  compliance  of the  Rubricator’s subject  and  structural organization to the current  status  and trends  of scientific knowledge  and technologies.  The main  stages  of the  accomplished studies  are  described:  comparative intellectual analysis of subject  scope and hierarchy of GRNTI classes  and thematic description  of sections  within  the  Plan  of Fundamental and  Thematic  Scientific Research  for 2021–2030; submitting proposals  for GRNTI by researchers of relevant research  institutes and STI agencies;  analyzing and content editing  of GRNTI proposals, eliminating concept  duplication, and updating  links and references.  The authors  include  the  statistics of changes  distribution in  GRNTI  2021 by types: changed  subject  headings, new headings  introduction, and elimination of the  subject headings.  Statistical  indicators  are analyzed  to characterize GRNTI subject  and structural organization, as well as its thematic classes (2nd  and 3rd  level headings).В статье представлены  результаты исследований  по обновлению и совершенствованию  действующей эталонной  версии  Государственного рубрикатора научно-технической информации  (ГРНТИ) – версии 2021 г. и формированию Основной классификационной  таблицы эталонной версии ГРНТИ 2022 г. Определены  основные  функции ГРНТИ  как базовой  классификации  Государственной системы научно-технической информации, эффективность которых зависит от уровня соответствия тематической и структурной организации  рубрикатора  современному  состоянию и тенденциям  развития  научного и технического знания. Перечислены основные этапы выполненных исследований: сопоставительный  интеллектуальный анализ  тематики и иерархической организации классов ГРНТИ и тематических описаний разделов  направлений  Плана фундаментальных  и поисковых  научных исследований  на 2021–2030 гг.; инициация  предложений  по  развитию  ГРНТИ  со  стороны  учёных-исследователей профильных  научных организаций  и органов  НТИ; анализ  и научное редактирование предложений  по развитию ГРНТИ, устранение дублирования понятий, актуализация ссылочно-справочного  аппарата. Представлена статистика распределения изменений, внесённых  в версию ГРНТИ 2021 г., по видам:  изменение   названия  рубрики,  введение   новой  рубрики,  исключение рубрики. Выполнен анализ статистических показателей,  характеризующих  развитие тематической  и структурной организации  разделов  ГРНТИ, а также его тематических классов (рубрик 2-го и 3-го уровней)

Preclinical studies of antiviral activity of the RPH-137 fusion protein and molnupiravir against COVID-19

Finding effective and safe medicines to fight SARS-CoV-2 infection is an urgent task. RPH-137 is an original trap fusion protein against SARS-CoV-2 virus. It comprises the angiotensin-converting enzyme type 2 extracellular domain and the human IgG1 Fc fragment.The aim of the study was to carry out a preclinical evaluation of the efficacy of RPH-137 and molnupiravir against SARS-CoV-2 infection.Materials and methods: the authors analysed RPH-137 expressed in a stable CHO cell line and molnupiravir used as an active pharmaceutical ingredient. Drug-mediated inhibition of virus-induced cytotoxicity was assessed in Vero cell culture. In vivo efficacy assessments were performed in Syrian hamsters. The animals were infected intranasally with SARS-CoV-2 (PIK35 clinical isolate) in the dose of 5 log TCID50. The authors evaluated body weight measurements, lung–body weight ratios, and lung histopathology findings and determined viral RNA levels in oropharyngeal swabs by RT-PCR using the amplification cycle threshold (Ct). The statistical analyses involved one- and two-way ANOVA, Student's t-test, and Mann–Whitney test.Results: RPH-137 and molnupiravir inhibited the cytopathic effect of SARS-CoV-2 in Vero cells; the EC50 values of RPH-137 amounted to 4.69 μg/mL (21.3 nM) and 16.24 μg/mL (73.8 nM) for 50 TCID50 and 200 TCID50, respectively, whereas the EC50 values of molnupiravir were 0.63 μg/mL (1900 nM) for both doses. Intramuscular RPH-137 (30 and 80 mg/kg) had no effect on the infection process in Syrian hamsters. The comparison with the challenge control group showed that intraperitoneal RPH-137 (100 mg/kg) had statistically significant effects on a number of parameters, including a 27% reduction in inflammation and a 30% reduction in the total lesion area of the lungs by Day 7. Intragastric molnupiravir (300 mg/kg twice daily) significantly inhibited SARS-CoV-2 infection.Conclusions: both RPH-137 and molnupiravir inhibited the cytopathic effect of SARS-CoV-2 in Vero cells. In Syrian hamsters, molnupiravir demonstrated a more pronounced inhibition of SARS-CoV-2 infection than RPH-137. However, RPH-137 had statistically significant effects on a range of parameters. This offers additional perspectives for further research

Доклинические исследования противовирусной активности гибридного белка RPH-137 и молнупиравира в отношении COVID-19

Finding effective and safe medicines to fight SARS-CoV-2 infection is an urgent task. RPH-137 is an original trap fusion protein against SARS-CoV-2 virus. It comprises the angiotensin-converting enzyme type 2 extracellular domain and the human IgG1 Fc fragment.The aim of the study was to carry out a preclinical evaluation of the efficacy of RPH-137 and molnupiravir against SARS-CoV-2 infection.Materials and methods: the authors analysed RPH-137 expressed in a stable CHO cell line and molnupiravir used as an active pharmaceutical ingredient. Drug-mediated inhibition of virus-induced cytotoxicity was assessed in Vero cell culture. In vivo efficacy assessments were performed in Syrian hamsters. The animals were infected intranasally with SARS-CoV-2 (PIK35 clinical isolate) in the dose of 5 log TCID50. The authors evaluated body weight measurements, lung–body weight ratios, and lung histopathology findings and determined viral RNA levels in oropharyngeal swabs by RT-PCR using the amplification cycle threshold (Ct). The statistical analyses involved one- and two-way ANOVA, Student's t-test, and Mann–Whitney test.Results: RPH-137 and molnupiravir inhibited the cytopathic effect of SARS-CoV-2 in Vero cells; the EC50 values of RPH-137 amounted to 4.69 μg/mL (21.3 nM) and 16.24 μg/mL (73.8 nM) for 50 TCID50 and 200 TCID50, respectively, whereas the EC50 values of molnupiravir were 0.63 μg/mL (1900 nM) for both doses. Intramuscular RPH-137 (30 and 80 mg/kg) had no effect on the infection process in Syrian hamsters. The comparison with the challenge control group showed that intraperitoneal RPH-137 (100 mg/kg) had statistically significant effects on a number of parameters, including a 27% reduction in inflammation and a 30% reduction in the total lesion area of the lungs by Day 7. Intragastric molnupiravir (300 mg/kg twice daily) significantly inhibited SARS-CoV-2 infection.Conclusions: both RPH-137 and molnupiravir inhibited the cytopathic effect of SARS-CoV-2 in Vero cells. In Syrian hamsters, molnupiravir demonstrated a more pronounced inhibition of SARS-CoV-2 infection than RPH-137. However, RPH-137 had statistically significant effects on a range of parameters. This offers additional perspectives for further research.Поиск эффективных и безопасных лекарственных средств для борьбы с коронавирусной инфекцией, вызванной вирусом SARS-CoV-2, является актуальной задачей. RPH-137 – оригинальный гибридный белок-ловушка вируса SARS-CoV-2, состоящий из внеклеточного домена ангиотензинпревращающего фермента 2 типа и Fc-фрагмента IgG1 человека.Цель работы: доклиническая оценка эффективности RPH-137 и молнупиравира в отношении инфекции, вызванной SARS-CoV-2.Материалы и методы: RPH-137 получали в стабильной линии клеток китайского хомячка. В работе использовали субстанцию молнупиравира. Изучение ингибирования вирус-индуцированной цитотоксичности проводили в культуре клеток Vero. В исследовании эффективности in vivo сирийских хомячков заражали интраназально SARS-CoV-2 (вариант ПИК35) в дозе 5 lg ТЦД50. Оценивали массу тела, массовый коэффициент и гистологическую картину легких. В орофарингеальных мазках измеряли содержание вирусной РНК методом ОТ-ПЦР по показателю порогового цикла амплификации Ct. Статистическая обработка: однофакторный и двухфакторный дисперсионный анализ (ANOVA), t-тест Стьюдента, критерий Манна–Уитни.Результаты: RPH-137 и молнупиравир ингибировали цитопатическое действие вируса SARS-CoV-2 в культуре клеток Vero: для RPH-137 EC50=4,69 мкг/мл (21,3 нМ) и 16,24 мкг/мл (73,8 нМ) для доз 50 ТЦД50 и 200 ТЦД50 соответственно, для молнупиравира EC50=0,63 мкг/мл (1900 нМ) для обеих доз вируса. RPH-137 при внутримышечном введении в дозах 30 и 80 мг/кг не оказывал влияния на развитие инфекции у сирийских хомячков. RPH-137 при внутрибрюшинном введении в дозе 100 мг/кг показал статистически значимый эффект по ряду параметров по сравнению с животными контрольной группы (контроль заражения), в том числе вызывая снижение воспалительного процесса и общей площади поражения легких на 7 сут на 27 и 30% соответственно. Молнупиравир при пероральном введении в дозе 300 мг/кг 2 раза в сутки значимо подавлял развитие инфекции, вызванной SARS-CoV-2.Выводы: RPH-137 и  молнупиравир ингибируют цитопатическое действие вируса SARS-CoV-2 в культуре клеток Vero. У сирийских хомячков введение молнупиравира демонстрировало более выраженное подавление инфекции, вызванной SARS-CoV-2, по сравнению с RPH-137. Однако RPH-137 проявлял статистически значимое действие по ряду параметров, что открывает перспективы для его дальнейшего изучения.