Assessing copy number abnormalities and copy-neutral loss-of-heterozygosity across the genome as best practice in diagnostic evaluation of acute myeloid leukemia: An evidence-based review from the cancer genomics consortium (CGC) myeloid neoplasms working group

Structural genomic abnormalities, including balanced chromosomal rearrangements, copy number gains and losses and copy-neutral loss-of-heterozygosity (CN-LOH) represent an important category of diagnostic, prognostic and therapeutic markers in acute myeloid leukemia (AML). Genome-wide evaluation for copy number abnormalities (CNAs) is at present performed by karyotype analysis which has low resolution and is unobtainable in a subset of cases. Furthermore, examination for possible CN-LOH in leukemia cells is at present not routinely performed in the clinical setting. Chromosomal microarray (CMA) analysis is a widely available assay for CNAs and CN-LOH in diagnostic laboratories, but there are currently no guidelines how to best incorporate this technology into clinical testing algorithms for neoplastic diseases including AML. The Cancer Genomics Consortium Working Group for Myeloid Neoplasms performed an extensive review of peer-reviewed publications focused on CMA analysis in AML. Here we summarize evidence regarding clinical utility of CMA analysis in AML extracted from published data, and provide recommendations for optimal utilization of CMA testing in the diagnostic workup. In addition, we provide a list of CNAs and CN-LOH regions which have documented clinical significance in diagnosis, prognosis and treatment decisions in AML

Robust Target Gene Discovery through Transcriptome Perturbations and Genome-Wide Enhancer Predictions in Drosophila Uncovers a Regulatory Basis for Sensory Specification

CisTarget X is a novel computational method that accurately predicts Atonal governed regulatory networks in the retina of the fruit fly

Региональная адаптация федеральной модели оплаты медицинской помощи по клинико-статистическим группам на примере случаев госпитализации пациентов, требующих назначения генно-инженерных биологических препаратов

The existing model of financial support of medical assistance for clinical-statistical groups (CSGs) in 2018 provides for the reimbursement for hospital stay expenses by the compulsory medical insurance fund in patients claiming the need for genetically engineered biological products (GiBP) during their stay in a day-care or 24-hour inpatient facility. The payment is made to CSG no. 121 in a day care and to CSG no. 316 in a 24-hour inpatient facility. The heterogeneity of the expenses for therapy with GiBP necessitates further division of the Federal CSGs into subgroups located in the constituent parts of the Russian Federation. This process has been initiated in some parts of the country, and it is seen as a way of regional adaptation of the Federal Medical insurance model. The proposed subdivision of the Federal CSGs allows for setting the tariffs reflecting the real expenses incurred by a local medical organization due to the therapeutic use of GiBP. The models of such specific CSGs proposed by RF subjects (after an expert evaluation) can be taken as a basis for updating the Federal CSG model, taking into account the differences in the costs of different drug therapy regimens.Модель финансирования медицинской помощи по клинико-статистическим группам (КСГ) в 2018 г. предусматривает оплату случаев госпитализации пациентов, требующих назначение генно-инженерных биологических препаратов (ГИБП) в условиях дневного и круглосуточного стационара за счет средств системы общего медицинского страхования (ОМС). Оплата осуществляется в рамках КСГ №121 в дневном стационаре и КСГ №316 в круглосуточном стационаре. Стоимостная разнородность лекарственной терапии ГИБП обуславливает начатое в части субъектов РФ выделение подгрупп в составе федеральных КСГ, представляющее собой один из способов региональной адаптации модели, предложенный на федеральном уровне. Разукрупнение федеральных КСГ позволяет устанавливать тарифы в зависимости от фактически понесенных медицинской организацией затрат на лекарственную терапию ГИБП. Предложенные в субъектах РФ модели разукрупнения КСГ для назначения ГИБП после экспертной проработки могут быть взяты за основу актуализации федеральной модели КСГ, учитывающей различия в стоимости схем лекарственной терапии

A comparison of the radiosensitisation ability of 22 different element metal oxide nanoparticles using clinical megavoltage X-rays

Background: A wide range of nanoparticles (NPs), composed of different elements and their compounds, are being developed by several groups as possible radiosensitisers, with some already in clinical trials. However, no systematic experimental survey of the clinical X-ray radiosensitising potential of different element nanoparticles has been made. Here, we directly compare the irradiation-induced (10 Gy of 6-MV X-ray photon) production of hydroxyl radicals, superoxide anion radicals and singlet oxygen in aqueous solutions of the following metal oxide nanoparticles: Al2O3, SiO2, Sc2O3, TiO2, V2O5, Cr2O3, MnO2, Fe3O4, CoO, NiO, CuO, ZnO, ZrO2, MoO3, Nd2O3, Sm2O3, Eu2O3, Gd2O3, Tb4O7, Dy2O3, Er2O3 and HfO2. We also examine DNA damage due to these NPs in unirradiated and irradiated conditions. Results: Without any X-rays, several NPs produced more radicals than water alone. Thus, V2O5 NPs produced around 5-times more hydroxyl radicals and superoxide radicals. MnO2 NPs produced around 10-times more superoxide anions and Tb4O7 produced around 3-times more singlet oxygen. Lanthanides produce fewer hydroxyl radicals than water. Following irradiation, V2O5 NPs produced nearly 10-times more hydroxyl radicals than water. Changes in radical concentrations were determined by subtracting unirradiated values from irradiated values. These were then compared with irradiation-induced changes in water only. Irradiation-specific increases in hydroxyl radical were seen with most NPs, but these were only significantly above the values of water for V2O5, while the Lanthanides showed irradiation-specific decreases in hydroxyl radical, compared to water. Only TiO2 showed a trend of irradiation-specific increase in superoxides, while V2O5, MnO2, CoO, CuO, MoO3 and Tb4O7 all demonstrated significant irradiation-specific decreases in superoxide, compared to water. No irradiation-specific increases in singlet oxygen were seen, but V2O5, NiO, CuO, MoO3 and the lanthanides demonstrated irradiation-specific decreases in singlet oxygen, compared to water. MoO3 and CuO produced DNA damage in the absence of radiation, while the highest irradiation-specific DNA damage was observed with CuO. In contrast, MnO2, Fe3O4 and CoO were slightly protective against irradiation-induced DNA damage. Conclusions: Beyond identifying promising metal oxide NP radiosensitisers and radioprotectors, our broad comparisons reveal unexpected differences that suggest the surface chemistry of NP radiosensitisers is an important criterion for their success

Вопросы патоморфогенеза новой коронавирусной инфекции (COVID-19)

Relevance of the problem of a new COVID-19 coronavirus infection is obvious. Among its most important aspects that require special study, are pathogenesis and morphological changes in severe forms of the disease.Material and methods. The analysis of 18 autopsy observations was carried out. Along with routine assessment of macro – and microscopic changes, immunohistochemical studies of lungs and other organs were performed using sera against antigens CD2,3,4,5,7, 20,31,34, 56,57,69; the presence of Fe2+ and Fe3+ was detected in the lungs and liver. Results. Structural changes in the lungs may be associated with cytopathic and cytoproliferative effects of the virus with damage to both the ciliary and alveolar epithelium, as well as the formation of hyaline membranes. Cellular infiltration is mainly represented by suppressor populations of T-lymphocytes and macrophages. Endothelial damage, vascular thrombosis of vessels of different calibers, and hemorrhages were detected. Many organs (lymph nodes, spleen, intestines, brain, adrenal glands) show changes that may indicate generalization of viral infection, and infiltrationof CD8+ lymphocytes in the kidneys, liver, adrenal glands, pericardium,and intestines indicates a probable autoimmune component of pathogenesis. In the liver and lungs deceased from COVID-19 only small clusters of Fe3+ and Fe2+ granules were detected, which can be associated (including in our control observation) with liver damage in malaria.  Новая коронавирусная инфекция (COVID-19) представляет собой глобальную проблему человечества. Среди её важнейших аспектов, требующих углублённого изучения, – патогенез и морфологические изменения при тяжелых формах заболевания.Материалы и методы. Проведен анализ 18 летально закончившихся случаев. Наряду с рутинной оценкой макро- и микроскопических изменений, проведено иммуногистохимическое исследование легких и других органов с использованием сывороток к СD 2, 3, 4, 5, 7, 20, 31, 34, 56, 57, 69, также в легких и печени выявлялось наличие Fe2+ и Fe3+.Результаты. Показаны характерные структурные изменения легких, которые могут быть связаны с цитопатическим и цитопролиферативным действием вируса с поражением как мерцательного, так и альвеолярного эпителия, а также формированием гиалиновых мембран. Клеточная инфильтрация представлена преимущественно супрессорными популяциями Т-лимфоцитов и макрофагами. Выявлены повреждения эндотелия, тромбоз сосудов разного калибра и кровоизлияния. Во многих органах (лимфатических узлах, селезенке, кишечнике, головном мозге, надпочечниках) обнаружены изменения, возможно, свидетельствующие о генерализации вирусной инфекции, а инфильтрация CD8+ лимфоцитами в почках, печени, надпочечниках, перикарде, кишечнике свидетельствует о вероятном аутоиммунном компоненте патогенеза. В печени и легких умерших от COVID-19 не выявлено значимого скопления гранул Fe3+и Fe2+

Разработка и изучение отраслевого стандартного образца активности вакцины против краснухи

Presents information on 1st series of branch standard sample to characterization the quality of the candidate of branch standard sample tested for performance evaluation: specific activity of authenticity, a description of sterility, presence of mycoplasma, loss on drying, pH, filling accuracy, the residual oxygen content in the vials. Attested feature of the new series of the standard sample is a specific activity, because the purpose of the of branch reference standard activity live Rubella vaccine is the suitability of the results of determining the specific activity of the Rubella virus in vaccines. Indicator specific activity of the candidate in the of branch reference standard was assessed by interlaboratory studies compared to current 1st standard sample of the enterprise and 1st International Reference Reagent For Rubella (Live) NIBSC-91/688. Certified value of the index is set «Specific activity of branch reference standard activity for rubella (4,63±0,50) lgCCE50/0,5 ml. Shelf-life stated by using test accelerated the degradation is not less than at minus 20°C.Представлены материалы по аттестации первой серии отраслевого стандартного образца (ОСО) активности вакцины против краснухи. Для характеристики качества кандидата в ОСО проведены испытания по оценке показателей: специфическая активность, подлинность, описание, стерильность, присутствие микоплазм, потеря в массе при высушивании, рН, точность наполнения, остаточное содержание кислорода в ампулах. Аттестуемой характеристикой стандартного образца является специфическая активность. Назначение ОСО активности вакцины против краснухи - это оценка приемлемости результатов определения активности вируса краснухи в вакцинах. Показатель «Специфическая активность» кандидата в ОСО оценивали по результатам межлабораторных исследований в сравнении со стандартным образцом предприятия и международным стандартом: 1st International Reference Reagent For Rubella (Live) NIBSC-91/688. Установлено аттестованное значение показателя «Специфическая активность» ОСО активности вакцины против краснухи: (4,63±0,50)lg ТЦД50/0,5 мл. Срок годности, установленный с помощью теста ускоренного старения, при условии хранения при минус 20°С, - не менее 5 лет. Результаты мониторинга стабильности ОСО подтверждают его стабильность за период наблюдения