Amino acids adsorption in differently aged and concentrated aqueous suspensions of ZnO and TiO[2] nanoparticles

Amino acids may be effectively used for preventing aggregation of engineered nanoparticles (NPs) in aqueous suspensions. This paper is primarily focused on the influence of exposure duration and particles content on adsorption coefficient (Ads) for ZnO and TiO[2] nanoparticles with an average size of 40-60 nm exposed to 2M aqueous solutions of glycine and L-glutamic acid. The value of Ads was estimated from surfactant concentration related to the intensity of infrared peak spectroscopy at 1300-1400 cm{−1}. It has been shown that in more concentrated suspensions (0.08-0.12 g/mL) Ads has ±5% fluctuation in measurement error' interval, whereas in less concentrated systems (0.02-0.04 g/mL) 3...20 h exposure of NPs may result in slight desorption of surfactant as shown for ZnO NPs or total desorption of surfactant as shown for TiO[2] NPs in glycine solutions. Six times decrease of 0.02 g/mL NPs concentration leads to Ads augmentation by 3-4 and 1.5{-6} times, respectively, on ZnO and TiO[2] nanoparticles. From a methodological view point, it has been concluded that in order to provide effective comparative study of NPs adsorption properties it is not reasonable to concentrate the NPs suspension more than 0.04 g/mL and it is better to expose them during 3 h in order to avoid surfactant desorption

Опыт применения генозаместительной терапии препаратом Золгенсма® (онасемноген абепарвовек) в реальной клинической практике в России

Objective: to analyze the safety and evaluate the effectiveness of therapy with onasemnogene abeparvovec in patients with spinal muscular atrophy in real clinical practice based on the experience of using the drug in the neuromuscular center of Research Clinical Pediatric Institute of Pirogov Russian National Research Medical University.Materials and methods. Patients with spinal muscular atrophy received therapy with onasemnogene abeparvovec based on the prescription of the drug according to vital indications by a council of physicians of Federal institutions (the availability of the drug was carried out within the framework of the MAP Program (global program of managed access MAP to AVXS-101 for eligible patients in countries, where it is not approved by regulatory authorities (NCT03955679), through funding from the charitable foundations, as well as through funding from the state fund “Circle of Kindness”. The drug tolerance was assessed and the analysis of side effects after drug administration was based on the criteria for adverse events (General criteria Adverse Event Terminology (CTCAE) v. 5.0) Patient motor function was assessed prior to treatment initiation and every 3–6 months after therapy using the Philadelphia Pediatric Hospital’s CHOP INTEND scale, total motor development based on Hammersmith Hospital Neurological Assessment Scale in Young Children, Part 2 (HINE-2), and the acquisition of new motor skills.Results. 41 children aged 5 to 47 months (weighing no more than 21 kg) received therapy with onasemnogene abeparvovec in the period from April 2020 to December 2021. Adverse events (hyperthermia, decreased appetite, nausea, vomiting) were registered in all patients with different degree of severity. Elevated levels of transaminases greater than 2 times the upper limit of the normal range were observed in 32 patients (78 %), thrombocytopenia in 9 patients (22 %). 15 patients (36 %) required a dose adjustment of corticosteroids.17 patients underwent assessment of motor scales after 6 months, 10 children were assessed after a year. The average improvement on the HINE-2 scale was 3.3 / 4.4 points, respectively. The average improvement on the CHOP INTEND Scale was 7.1 / 9.4 points after 6 / 12 months of therapy.Conclusion. The efficacy and safety of onasemnogene abeparvovec have been demonstrated in real clinical practice in the treatment of spinal muscular atrophy for children in different age groups with a body weight of no more than 21 kg.Цель исследования – проанализировать безопасность и оценить эффективность терапии препаратом Золгенсма® (онасемноген абепарвовек) у пациентов со спинальной мышечной атрофией в реальной клинической практике на основании опыта применения препарата в нервно-мышечном центре ОСП «Научно-исследовательский клинический институт педиатрии им. акад. Ю. Е. Вельтищева» ФГБОУ ВО РНИМУ им. Н. И. Пирогова.Материалы и методы. Пациенты со спинальной мышечной атрофией получали терапию препаратом онасемноген абепарвовек на основании назначения препарата по жизненным показаниям консилиумом врачей федеральных учреждений (доступность к препарату осуществлялась в рамках Программы MAP (глобальная программа управляемого доступа MAP к препарату AVXS-101 для пациентов, соответствующих критериям, в странах, где он не был одобрен регулирующими органами (NCT03955679)), за счет финансирования благотворительных фондов, а также за счет финансирования государственным фондом «Круг добра». Проведены оценка переносимости препарата и анализ побочных эффектов после введения препарата на основании критериев нежелательных явлений (Общие критерии терминологии для нежелательных явлений (CTCAE) v. 5.0). Оценивались моторная функция пациентов до начала терапии и каждые 3–6 мес после терапии с помощью шкалы детской больницы Филадельфии для диагностики двигательных функций у новорожденных (CHOP INTEND), общее двигательное развитие по шкале оценки неврологического статуса больницы Хаммерсмит у детей раннего возраста, часть 2 (HINE-2), а также приобретение новых двигательных навыков.Результаты. Терапию препаратом онасемноген абепарвовек получил 41 ребенок в возрасте от 5 до 47 мес (с массой тела не более 21 кг) в период с апреля 2020 г. по декабрь 2021 г. Нежелательные явления (гипертермия, снижение аппетита, тошнота, рвота) зарегистрированы у всех пациентов с разной степенью выраженности. Повышение уровня трансаминаз более чем в 2 раза от верхней границы нормы было отмечено у 32 (78 %) пациентов, тромбоцитопения – у 9 (22 %); 15 (36 %) пациентам потребовалась коррекция дозы кортикостероидов.Семнадцати пациентам проведена оценка по двигательным шкалам через 6 мес, 10 детям – спустя год. Среднее улучшение по шкале HINE-2 составило 3,3 / 4,4 балла соответственно. Среднее улучшение по шкале CHOP INTEND составило 7,1 / 9,4 балла через 6 / 12 мес терапии.Заключение. Продемонстрированы эффективность и безопасность применения препарата онасемноген абепарвовек в условиях реальной клинической практики при терапии спинальной мышечной атрофии для детей в разных возрастных группах с массой тела не более 21 кг

The prospects of working with patients on smoking cessation

The research features the study of the influence of smoking on organs and organ systems. This article also has a defined profile of smokers, among whom psychological help in smoking cessation shows the highest effect.Исследование посвящено изучению влияния курения на системы и органы. Так же в статье сформирован портрет курильщика, которому помощь в отказе от курения будет более эффективной

The prospects of working with patients on smoking cessation

The research features the study of the influence of smoking on organs and organ systems. This article also has a defined profile of smokers, among whom psychological help in smoking cessation shows the highest effect.Исследование посвящено изучению влияния курения на системы и органы. Так же в статье сформирован портрет курильщика, которому помощь в отказе от курения будет более эффективной

Изотопный состав зимних атмосферных осадков и снежного покрова в предгорьях Алтая

Over the past three decades, several general circulation models of the atmosphere and ocean (atmospheric and oceanic general circulation models  – GCMs) have been improved by modeling the hydrological cycle with the use of isotopologues (isotopes of water) HDO and H2 18O. Input parameters for the GCM models taking into account changes in the isotope composition of atmospheric precipitation were, above all, the results obtained by the network GNIP – Global Network of Isotopes in Precipitation. At different times, on the vast territory of Russia there were only about 40 simultaneously functioning stations where the sampling of atmospheric precipitation was performed. In this study we present the results of the isotope composition of samples taken on the foothills of the Altai during two winter seasons of 2014/15 and 2015/16. Values of the isotope composition of precipitation changed in a wide range and their maximum fluctuations were 25, 202 and 18‰ for δ18О, dexc and δD, respectively. The weighted-mean values of δ18О and δD of the precipitation analyzed for the above two seasons were close to each other (−21.1 and −158.1‰ for the first season and −21.1 and −161.9‰ for the second one), while dexc values differed significantly. The comparison of the results of isotope analysis of the snow cover integral samples with the corresponding in the time interval the weighted-mean values of precipitation showed high consistency. However, despite the similarity of values of δ18О and δD, calculated for precipitation and snow cover, and the results, interpolated in IsoMAP (from data of the GNIP stations for 1960–2010), the dexc values were close to mean annual values of IsoMAP for only the second winter season. According to the trajectory analysis (the HYSPLIT model), the revealed differences between both, the seasons, and the long-term average values of IsoMAP, were associated with a change of main regions where the air masses carrying precipitation were formed, namely, the North Atlantic (the winter season of 2014/15) and the inland areas with open ice-free water bodies (the season of 2015/16). Thus, with the correct interpretation of the results, the data on the snow cover isotope composition on the Altai foothills can be used as an alternative data sources instead of the GNIP data.Приводятся результаты изотопного анализа состава атмосферных осадков и снежного покрова предгорий Алтая. Показано, что средневзвешенные значения осадков двух зимних сезонов (2014/15 и 2015/16 гг.) для δ18О составили −21,1‰, а для δD −158,1 и −161,9‰ соответственно и хорошо согласуются с изотопным составом интегральных проб снежного покрова. Проявившиеся отличия в dexc, очевидно, связаны со сменой основных регионов формирования воздушных масс, приносящих атмосферные осадки: сменой открытых ото льда акваторий Северной Атлантики на внутриконтинентальные водоёмы. При корректной интерпретации результатов данные изотопного состава атмосферных осадков и снежного покрова в предгорьях Алтая могут быть использованы в ряде моделей МОЦ

Стабильные изотопы 18O и D в ключевых компонентах водного стока и криолитозоны Центральной Якутии (Восточная Сибирь)

On the basis of about 430 analyses, the 18O and D compositions (%o) of atmospheric precipitation, ground ice, surface and inter-permafrost underground waters of cryogenic-aeolian landscapes of Central Yakutia (Eastern Siberia) are discussed. Precipitation compositions here demonstrate a large annual variation (from -6.12 to -45.0 % for δ18O, and from -72.1 to -350.1 % for δD), and they are described by the Local Meteoric Water Line according to the equation δD = 7.81518O - 1.57). In winter and in the process of spring melting, the snow storage is subjected to a significant evaporative fractionation, that is expressed by the equation δD = 6.85518O - 31.9. The heaviest and deuterium-depleted compositions (δ18O = -19.3 %, δD = -160.9, dexc = -6.7 %) are found in the last snow patches in early June. The lightest compositions similar to the present-day winter precipitation (snow) are characteristic of the polygonal wedge ices (PWI) of the Central Yakutia. The most lightweight (from -30 to -34 % for δ18O, and from 240 to 275% for δ D) were established to be typical for the ancient PWI, dated by the first half of the Late Pleistocene (MIS 3-4). Heavier compositions (δ18O = -27.2±1.4, δD = -215.8±8.5, dexc = 1.7±3.1 %) with obvious features of evaporative fractionation correspond to younger PWI (MIS 2-1). The heaviest compositions (δ18O = -12.2±0.7, δD = -99.2±4.7, dexc = -2.0±0.8 %) and high angular coefficients of approximating equations were determined in the investigated cave ices of sublimation origin, that implies the atmospheric origin of them. The current processes of evaporative fractionation are the most intensively reflected in the waters of aeolian lakes (δ18O = -11.8±3.5, δD = -120.2±18.4, dexc = -25.8±10.5 %), and the compositions are described by the regression equation 5D = 5.52 δ18O - 54.12 (R2 = 0.97). The phenomenal objects of the cryogenic-eolian landscapes of the Central Yakutia are high-debit underground sources. Among all other components of the water flows, composition of these sources is the most stable (δ18O = -21.6±0.8, δD = -172.6±5.1, dexc = 0.23±3.0 %). The regression of compositions of the largest underground source Bulus is approximated by the equation 5D = 6.31 δ18O - 36.7 (R2 = 0.78), that is indicative to significant evaporative fractionation and close relation with the aeolian lakes in the alimentation area.Особенности рельефа и строения криолитозоны Центральной Якутии связаны с широким распространением здесь позднечетвертичных супесчаных дюнных покровов. Они вмещают разветвлённые сети обводнённых межмерзлотных таликов, гидравлически связанных эоловых озёр, подземных источников, фрагменты едомных отложений с мощными ледяными жилами, а также наледи. На основе выборки более чем из 430 определений обсуждается разнообразие состава стабильных изотопов (18O и D) перечисленных компонентов водного стока

Изотопный состав и регионы-источники зимних осадков в Надымской низменности

According to the forecast of IPCC (Intergovernmental Panel of the Climate Change), an increase in precipitation is expected in this century in the Arctic. The main reason is intensification of evaporation from waters of the Arctic Ocean opening due to the intensive melting of sea ice. It is supposed that these changes will be most severe in winters in the Arctic regions, which are subject to significant anthropogenic load. In this respect, the intensively developed Nadym Lowland may be considered as a promising area for researches. The results of our study showed that the circulation conditions (primarily cyclones coming from the North Atlantic under the Eastern (E) circulation form of the G.Ya. Vangenheim–A.A. Girs classification) significantly influence on the isotopic composition of precipitation in this region. Thus, in the cold period of 2016–2017, the isotopic composition of precipitation changed for δ18О by 21 ‰, and for δD by 167 ‰ (weighted average values δ18О = −22.3 ‰, δD = −172.6 ‰, and dexc = 5.6 ‰). The use of the dew point temperature at the moment of precipitation in the calculations of the isotopic-temperature dependences allows obtaining the following coupling equation: δ18О = 0.67Tdp − 15.2 (R2 = 0.67). On the basis of the joint analysis of synoptic, trajectory and isotopic data, the main regions-sources of atmospheric moisture, precipitated in the Nadym Lowland during the cold period of 2016–2017, were determined. The major contributions were made by the Atlantic Ocean (35.7%), the North Atlantic Ocean and the Arctic Ocean (30.4%), and the Black Sea-Caspian region (20%). The last one is characterized by the most weighted isotopic composition. Inland source regions have contributed the least to precipitation (slightly larger 10%), and their lightweight isotopic composition is related to cryogenic fractionation.В результате совместного анализа синоптических, траекторных и изотопных данных определены основные регионы‑источники поступления атмосферной влаги, выпавшей в виде осадков в Надымской низменности. Наибольший вклад вносит Атлантический океан (35,7%), меньше – северная часть Атлантического океана и Северный Ледовитый океан (30,4%), а также Черноморско‑Каспийский регион (20%) и внутриконтинентальные регионы (немногим более 10%)

Fluorescent Protein-Based Methods for On-Plate Screening of Gene Insertion

Unlike the commonly used method of blue-white screening for gene insertion, a fluorescent protein-based screening method offers a gain-of-function screening process without using any co-factors and a gene fusion product with a fluorescent protein reporter that is further useful in cell imaging studies. However, complications related to protein-folding efficiencies of the gene insert in fusion with fluorescent protein reporters prevent effective on-plate bacterial colony selection leading to its limited use.Here, we present three methods to tackle this problem. Our first method promotes the folding of the gene insert by using an N-terminal protein such as calmodulin that is well folded and expressed. Under this method, fluorescence was increased more than 30x over control allowing for enhanced screening. Our second method creates a fluorescent protein that is N-terminal to the gene upon insertion, thereby reducing the dependency of the fluorescent protein reporter on the folding of the gene insert. Our third method eliminates any dependence of the fluorescent protein reporter on the folding of the gene insert by using a stop and start sequence for protein translation.The three methods together will expand the usefulness of fluorescence on-plate screening and offer a powerful alternative to blue-white screening