Coronavirus disease 2019 (COVID-19): NETosis-associated mechanisms of progression and prospects for therapy regulating the formation of neutrophil extracellular traps (NETs)

Infectious disease COVID-19 caused by the SARS-CoV-2 coronavirus is characterized by high contagiousness, complexity of pathogenesis and unpredictability of the clinical course. In severe cases, which are especially susceptible to men, the elderly and people with underlying medical conditions such as obesity, diabetes, hypertension, cardiovascular and chronic respiratory diseases, the infection leads to respiratory failure and death due to the development of an extensive inflammatory reaction. As a result of many studies, it has been established that one of the leading causes of the severe course and death of patients with COVID-19 is the development of coagulopathy, that is, increased thrombus formation in small vessels due to excessive activity of neutrophils, which form the so-called neutrophil extracellular traps (NETs). Although NETs play a useful role in protecting their host from pathogens, their overgrowth can trigger a cascade of adverse reactions including: the production of antibodies against the host’s DNA (autoimmunization); damage to surrounding tissue; or the occurrence of thromboembolic complications. Therefore, extracellular neutrophil traps and their markers have been identified as targets for new therapeutic strategies aimed at reducing the severity of COVID-19 disease and/or mortality. This article describes the structure of NETs, as well as analyzes the molecular mechanisms that contribute to their overgeneration. In addition, the prospects for COVID-19 therapy aimed at regulating the formation of extracellular traps by creating drugs both limiting the production of NET structures and dissolving their excess amounts in the body of patients are discussed

Ассоциация генов XRCC1, HMMR с развитием рака молочной железы в кыргызской популяции

An association of genes XRCC1 and HMMR with breast cancer (BC) has never been tested in the Kyrgyz ethnic group. This was a case-control study of 201 women of the Kyrgyz ethnic group with a morphologically verified breast cancer (N=99) and 102 controls age-matched with BC cases. The mean age of the patients was 53 years (24–74, SE mean = 0.967, STD=9.81). The extraction of DNA was carried out from venous blood. The genotyping was conducted by using the method of polymerase chain reaction and restriction fragment length polymorphism. When comparing the results of genotyping, the histological structure of the tumor and the «menopause» factor, Fisher»s exact test was used. Calculation of the odds ratio was carried out by cross tabulation method. A statistically significant link between the XRCC1 Arg194Trp polymorphism and the menopausal status was observed (p=0,018). The Arg / Arg genotype of XRCC1 Arg194Trp polymorphism occurred in 52 % of cases in women at menopausal age, whereas in women before the onset of menopause, the genotype Arg / Arg occurred in 78.8 % of BC cases (p=0.009). The CT genotype of HMMR V353A polymorphism was identified as “protective” factor – OR=0.481, 95 % CI [0.27‑0.85]. There was no statistically significant association between the results of genotyping and histological structure of the tumor, as well as the age of verification of the diagnosis of BC.Влияние генов XRCC1, HMMR на развитие рака молочной железы в кыргызской популяции ранее не было изучено. В исследовании приняли участие 99 женщин кыргызской этнической группы с морфологически верифицированным диагнозом рак молочной железы (РМЖ), получавшие стационарное лечение в Национальном центре онкологии и Диагностическом центре «КафМедЦентр» (г. Бишкек, Кыргызская Республика). Средний возраст пациентов составил 53 года (24–74, SE mean = 0,967, STD=9,81). В контрольную группу вошли 102 условно здоровые женщины кыргызской этнической группы, находящиеся в той же возрастной категории, что и исследуемые. Генотипирование осуществлялось методом ПЦР-ПДРФ. При сравнении результатов генотипирования, гистологической структуры опухоли и фактора «менопауза» использовался точный критерий Фишера. Расчет отношения шансов проводился путем построения таблицы кросс-табуляции. Показано, что для генотипа Arg / Arg полиморфного локуса Arg194Trp гена XRCC1 имеется статистически значимая ассоциация с фактором «менопауза». У женщин в менопаузе генотип Аrg / Arg полиморфного локуса Arg194Trp гена XRCC1 встречается с частотой 52 %, тогда как у женщин до наступления менопаузы этот же генотип встречается с частотой 78,8 % (р=0,009). Также было установлено, что генотип СС полиморфного локуса V353A гена HMMR является «протективным» фактором и ассоциирован с низким риском развития РМЖ в  кыргызской популяции (ОШ=0,481, 95 % ДИ=0,272–0,850). Кроме того, не было выявлено статистически значимой ассоциации между результатами генотипирования и гистологической структурой опухоли, а также возрастом верификации диагноза

Doing Gender Online : Digital Spaces for Identity Politics

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A new Time-of-flight detector for the R 3 B setup

© 2022, The Author(s).We present the design, prototype developments and test results of the new time-of-flight detector (ToFD) which is part of the R3B experimental setup at GSI and FAIR, Darmstadt, Germany. The ToFD detector is able to detect heavy-ion residues of all charges at relativistic energies with a relative energy precision σΔE/ ΔE of up to 1% and a time precision of up to 14 ps (sigma). Together with an elaborate particle-tracking system, the full identification of relativistic ions from hydrogen up to uranium in mass and nuclear charge is possible.11Nsciescopu