БРОУНОВСКАЯ ДИФФУЗИЯ НАНОЧАСТИЦ ВНУТРИ СФЕРИЧЕСКОЙ КАПЛИ ПЕРЕМЕННОГО РАДИУСА

The influence of Brownian diffusion on the distribution of nanoparticles in an evaporating or growing micron droplet is considered. It is shown that there are possibilities for emerging a spatially non-uniform state of the nanoparticles in the droplet.Исследовано влияние броуновской диффузии на распределение наночастиц внутри испаряющейся и растущей микронной капли. Показано, что возможно возникновение пространственно неоднородных распределений наночастиц в капле

Molecular genetic features of the development of restrictive cardiomyopathy in Russian children

Aim. To identify the proportion of restrictive cardiomyopathy (RCM), as well as cardiomyopathy (CMP) with a restrictive type of hemodynamics among all cases of genetic CMP and to determine the relative frequencies and spectrum of nucleotide variants in Russian children with RCM, as well as to search for phenogenotypic correlations.Material and methods. The study included 689 children with CMPs. All children underwent a molecular genetic testing of the target regions of 419 genes responsible for various cardiomyopathies and channelopathies using the method of massively parallel sequencing (MPS).Results. In 668 (97,0%) children, pathogenic, likely pathogenic nucleotide variants, as well as nucleotide variants with unknown clinical significance, were identified. Of these, 45 (6,7%) patients were selected to determine the molecular genetic characteristics of RCM, 20 of whom had clinical symptoms and morphofunctional structure of RCMP (3,0%), while the remaining 25 (3,7%) children were diagnosed with another CMP type with a restrictive type of hemodynamics. In total, these patients had 41 nucleotide variants in 15 different genes, while 19 (46,3%) variants were pathogenic, 12 (29,3%) — likely pathogenic, 10 (24,4%) — uncertain clinical significance. Pathogenic and likely pathogenic variants were identified in a total of 38 (84,4%) patients, while in 19 (42,2%) patients, the pathogenic variants described earlier were found. The most common genetic marker of RCM in Russian children was TNNI3 gene mutations. In total, they were identified in 12 (25%) children: with RCP — 8 (40%) patients; with CMP with a restrictive type of hemodynamics — 4 (16%) patients. At the same time, the most common mutation of the TNNI3 gene was the nucleotide variant c.575G>A, leading to the amino acid variant p.R192H, described earlier in patients with RCM and identified by us in three (15%) unrelated children with RCM. In addition, a significant difference was found between the averaged values of N-terminal pro-brain natriuretic peptide in patients with mutations in the MYH7 and TNNI3 genes (0,0039, p<0,05), as well as between the peak flow gradient values in children with mutations in TNNI3 and FLNC genes (0,0016, p<0,05), TNNI3 and MYH7 genes (0,039, p<0,05).Conclusion. The results of this study indicate a significant genetic heterogeneity of RCM in Russian children and the need for further research aimed at finding genotype-phenotype associations in order to predict the course of the disease and select the proper therapy

Оценка поражения легких при внебольничных пневмониях по данным магнитно-резонансной томографии при первичной диагностике и в ходе лечения

Purpose of the study. To evaluate the practical significance of MRI in the primary diagnosis of inflammatory lung diseases, as well as in follow-up control of treatment, also in comparison with the results of CT of the chest.Material and Methods. In 25 patients with acute pneumonia, six of them with acute myocardial infarction developed as complication of it, the MRI of the chest organs was performed in T1 - and T2-weighted (-w.) modes, also with fat signal suppression, with slice thickness of 2.5 to 5 mm, in a matrix of 256 × 256 or 256 ×392 pixels, with a scanning field of view as large as 40 x 40 cm. In T1-w. mode TR = 390–650 ms, TE = 10–15 ms. When T2-w. scanning, respectively, TR = 2900 -4000 ms, TE = 20–25 ms. Paramagnetic contrast enhancement was also carried out in 16 of 24 patients, at a dosage of 0.1 mmol/kg of body weight. Post-contrast images were acquired 12-17 minutes after the introduction of paramagnetic agent. In 17 out of 25 of our patients, chest CT was also performed.Results. The minimal cross-dimension of focal inflammatory lesions for community-acquired pneumonia, imaged with MRI chest scanning was as little as 9 х 21 mm. The dimensions of lung lesion obtained from the MRI scanning did correlate significantly with results of the CT (r = 0.96, p < 0.001). Also MRI of the lung did prove the successful cure of pneumonia. Also in six cases the MRI verified the acute myocardial infarction occurred as complication of severe pneumonia. Based on the results of MRI of the lungs and chest, the treatment strategy was supplemented in 16 cases and significantly changed in 9 cases.Conclusion. MRI of the lungs employing the T1- and T2-weighted protocols with fat suppression, diffusionweighted imaging and use of contrast enhancement delivers highly efficient technique of imaging of nodal, segment and lobe inflammation. MRI of the chest should be reasonably employed for diagnosis and follow-up of treatment in hospitals and diagnostic units possessing high- and middle-field MRI scanners able toacquire the images in breath-synchronised mode.Цель исследования: оценить практическую значимость МРТ в первичной диагностике воспалительных заболеваний легких, а также и в динамическом наблюдении – при инструментальном контроле лечения, в том числе в сравнении с результатами спиральной рентгеновской компьютерной томографии (СРКТ) органов грудной клетки.Материал и методы. У 25 пациентов с острой пневмонией, из них 6 – с развившимся на фоне ее острым инфарктом миокарда, была проведена МРТ органов грудной клетки в Т1- и Т2-взвешенных (взв.) режимах, в том числе с подавлением сигнала от жировой ткани, толщиной среза от 2,5 до 5 мм, в матрицу 256 х 256 или 256 х 392 элемента изображения, при поле сканирования 40 х 40 см. При Т1-взв. сканировании TR = 390–650 мс, TE = 10–15 мс. При Т2-взв. сканировании TR = 2900–4000 мс, TE = 20–25 мс соответственно. У 16 из 24 пациентов было выполнено также парамагнитное контрастное усиление в дозировке 0,1 ммоль/кг массы тела. Постконтрастные изображения записывались спустя 12–17 мин после введения парамагнитных контрастных средств. У 17 из 25 наших пациентов была выполнена также компьютерная томография органов грудной клетки.Результаты. Минимальный размер очаговых воспалительных поражений при внебольничной пневмонии, визуализированной средствами МРТ, составил 9 х 21 мм. Размеры патологического очага воспаления по данным МРТ легких высокодостоверно коррелировали с результатами СРКТ (r = 0,96, p < 0,001). МРТ легких достоверно верифицировали достижение ремиссии. В 6 случаях МРТ позволила также верифицировать острый инфаркт миокарда, развившийся на фоне долевой пневмонии. Тактика лечения по результатам проведения МРТ легких и грудной клетки была дополнена в 16 и значительно изменена в 9 случаях.Заключение. МРТ легких с использованием Т1-, Т2-взв. протоколов с подавлением сигнала от жировой ткани, диффузионно-взвешенных протоколов и в особенности с применением парамагнитного контрастного усиления представляет собой высокоэффективный метод визуализации очаговых, сегментарных и распространенных воспалительных поражений. МРТ органов грудной клетки обоснованно может быть использована для диагностики и оценки лечения воспалительных поражений легких во всех диагностических и лечебных учреждениях, располагающих как низко-, так и высокопольными МР-томографами с возможностями синхронизации записи с дыханием

Динамика частоты встречамости уропатогенов и антимикробных детерминант резистентности при детской значимой бактериурии в 2017 и 2019 годах: моноцентровое исследование

Urinary tract infections are the second most common infections in children with spreading of antimicrobial resistance among uropathogens currently poses a high epidemiological threat.Purpose. Analysis of species prevalence and the presence of genetic determinants of antibiotic resistance.Materials and methods. In the study 215 midstream urine samples were retrospectively analyzed. Samples were obtained during 2017 and 2019 from patients aged 4 weeks to 17 years at the National Medical Research Center for Children's Health Federal State Autonomous Institution of the Ministry of Health of the Russian Federation.Results. Species of pathogen were identified in 93 samples, while the bacterial composition of other samples was classified as «intestinal flora» (n = 17), «coccus flora» (n = 16) or «mixed flora» (n = 89). The most common types of uropathogens in monopathogenic infections in 2017 and 2019 were Escherichia coli (37.5% and 29.2%, respectively). Among infections caused by multiple pathogens, the most common etiological agents were Pseudomonas aeruginosa and Staphylococcus spp. Among all studied samples, 31.9% contained CTX-M-like genes, 5% VIM genes, 1.8% NDM genes, and 3.0% — OXA-48-like genes, and 5.6% of samples contained two and more genetic determinants associated with resistance, with the most prevalent gene combination being the combination of CTX-M- and OXA-48-like genes. In 69 samples with identified species of uropathogens, resistance profile to antimicrobial, determined by microbiological methods, correlated with detected resistance genetic determinants.Conclusion. Authors suggest that introduction of testing for the presence of genes associated with antibacterial resistance to general clinical practice would not only provide an opportunity to conduct epidemiological monitoring of the genetic determinants of antibiotic resistance, but also provide an opportunity to select the correct timely treatment of childhood bacteriuria caused by antibiotic-resistant infectious agents.Инфекции мочевыводящих путей (ИМП) являются вторыми по частоте встречаемости инфекциями у детей, в то время как распространение среди уропатогенов антимикробной резистентности представляет в настоящее время высокую эпидемиологическую угрозу.Цель. Провести анализ видового состава и наличия генетических детерминант антибиотикорезистентности.Материалы и методы. В ходе исследования был проведен ретроспективный анализ 215 образец средней порций мочи. Образцы были получены в течение 2017 и 2019 годов от пациентов в возрасте от 4 недель до 17 лет в ФГАУ «Национальный медицинский исследовательский Центр Здоровья Детей» Министерства здравоохранения Российской Федерации.Результаты. Видовая принадлежность патогенов была установлена в 93 образцах, в то время как бактериальный состав других образцов был классифицирован как «кишечная флора» (n = 17), «кокковая флора» (n = 16) или «смешанная флора» (n = 89). Наиболее распространенными видам уропатогенов при монопатогенных инфекциях в 2017 и 2019 являлась Escherichia coli (37,5% и 29,2%, соответственно). Среди инфекций, вызванных множественными патогенами, наиболее часто встречающимися этиологическими агентами являлись Pseudomonas aeruginosa и Staphylococcus spp. Среди всех исследованных образцов 31,9% содержали CTX-M-подобные гены, 5% гены VIM, 1,8% гены NDM, а также 3,0 % — OXA-48-подобные гены, а также 5,6% образцов содержали две и более генетические детерминанты, ассоциированные с резистентностью, при этом наиболее превалирующей комбинацией генов было сочетание CTX-M- и OXA-48-подобных генов. В 69 образцах с идентифицированными видами уропатогенов профиль устойчивости к противомикробным препаратам, определенный микробиологическими методами, соответствовал обнаруженным генам устойчивости.Выводы. Авторы полагают, что введение в общую клиническую практику тестирования на наличие генов, ассоциированных с антибактериальной резистентностью, предоставит не только возможность проведения эпидемиологического мониторинга за генетическими детерминантнами антибиотикоустойчивости, но также предоставит возможность подбирать корректное своевременное лечение детских бактериурий, вызванных антибиотикорезистентными инфекционными агентами

Derivatives of 9-phosphorylated acridine as butyrylcholinesterase inhibitors with antioxidant activity and the ability to inhibit β-amyloid self-aggregation: potential therapeutic agents for Alzheimer’s disease

We investigated the inhibitory activities of novel 9-phosphoryl-9,10-dihydroacridines and 9-phosphorylacridines against acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and carboxylesterase (CES). We also studied the abilities of the new compounds to interfere with the self-aggregation of β-amyloid (Aβ42) in the thioflavin test as well as their antioxidant activities in the ABTS and FRAP assays. We used molecular docking, molecular dynamics simulations, and quantum-chemical calculations to explain experimental results. All new compounds weakly inhibited AChE and off-target CES. Dihydroacridines with aryl substituents in the phosphoryl moiety inhibited BChE; the most active were the dibenzyloxy derivative 1d and its diphenethyl bioisostere 1e (IC50 = 2.90 ± 0.23 µM and 3.22 ± 0.25 µM, respectively). Only one acridine, 2d, an analog of dihydroacridine, 1d, was an effective BChE inhibitor (IC50 = 6.90 ± 0.55 μM), consistent with docking results. Dihydroacridines inhibited Aβ42 self-aggregation; 1d and 1e were the most active (58.9% ± 4.7% and 46.9% ± 4.2%, respectively). All dihydroacridines 1 demonstrated high ABTS•+-scavenging and iron-reducing activities comparable to Trolox, but acridines 2 were almost inactive. Observed features were well explained by quantum-chemical calculations. ADMET parameters calculated for all compounds predicted favorable intestinal absorption, good blood–brain barrier permeability, and low cardiac toxicity. Overall, the best results were obtained for two dihydroacridine derivatives 1d and 1e with dibenzyloxy and diphenethyl substituents in the phosphoryl moiety. These compounds displayed high inhibition of BChE activity and Aβ42 self-aggregation, high antioxidant activity, and favorable predicted ADMET profiles. Therefore, we consider 1d and 1e as lead compounds for further in-depth studies as potential anti-AD preparations

Equalization of the Concentration of a Scalar Impurity in a Flow‐Type Chamber

Experimental and theoretical investigations of the time of equalization of the concentration of an impurity in a rectangular flow‐type chamber have been carried out. It has been shown that the process of equalization of the concentration with time is exponential in character. The characteristic equalization time has been computed using the theory of turbulent diffusion. Theoretical results describe experimental regularities with an accuracy of about 10%. The value of the coefficient of turbulent diffusion for different configurations of flows in the chamber has been obtained from a comparison of experimental and calculated results