Polymorphism of genes associated with infectious lung diseases in Northern Asian populations and in patients with community-acquired pneumonia

The innate Iнн\mmune system is the first to respond to invading pathogens. It is responsible for invader recognition, immune-cell recruitment, adaptive-immunity activation, and regulation of inflammation intensity. Previously, two single-nucleotide polymorphisms of innate-immunity genes – rs5743708 (Arg753Gln) of the TLR2 gene and rs8177374 (Ser180Leu) of the TIRAP gene – have been shown to be associated with both pneumonia and tuberculosis in humans, but the data are contradictory among different ethnic groups. It has also been reported that rs10902158 at the PKP3-SIGGIR-TMEM16J genetic locus belongs to a haplotype race-specifically associated with tuberculosis. Meanwhile, a gradient of its frequency is observed in Asia. The aim of this work was to assess the effect of selection for the genotypes of the above-mentioned SNPs on the gene pools of populations living in harsh climatic conditions that contribute to the development of infectious lung diseases. We estimated the prevalence of these variants in white and Asian (Chukchis and Yakuts) population samples from Northern Asia and among patients with community-acquired pneumonia (CAP). Carriage of the rs5743708 A allele was found to predispose to severe CAP (odds ratio 2.77, p = 0.021), whereas the GG/CT genotype of rs5743708/rs8177374 proved to be protective against it (odds ratio 0.478, p = 0.022) in white patients. No association of rs10902158 with CAP (total or severe) was found among whites. Stratification of CAP by causative pathogen may help eliminate the current discrepancies between different studies. No significant difference in rs5743708 or rs8177374 was found between adolescent and long-lived white samples. Carriage of the alleles studied is probably not associated with predisposition to longevity among whites in Siberia. Both white and Asian populations studied were different from Western European and East Asian populations in the variants’ prevalence. The frequency of the rs8177374 T (Ser180Leu) variant was significantly higher in the Chukchi sample (p = 0, χ2 = 63.22) relative to the East Asian populations. This result may confirm the hypothesis about the selection of this allele in the course of human migration into areas with unfavorable climatic conditions

Meteoprotective properties of melaxen in old and middle aged patients with ischemic heart disease in combination with arterial hypertension

We studied 102 patients (mean age 60.1±3.3 years) with arterial hypertension (AH) II-III stage, grade 2-3 and ischemic heart disease (exertional angina functional class (FC) I-II, postinfarction cardiosclerosis). The control group of patients received traditional therapy (TT): beta -blockers, calcium channel blockers, ACE inhibitors, antiplatelet agents, diuretics and nitrate

Detection of Five New RRATs at 111 MHz

Results of 111-MHz monitoring observations carried out on the Big Scanning Antenna of the Pushchino Radio Astronomy Observatory during September 1-28, 2015 are presented. Fifty-four pulsating sources were detected at declinations $-9^o < \delta < +42^o$. Forty-seven of these are known pulsars, five are new sources, and two are previously discovered transients. Estimates of the peak flux densities and dispersion measures are presented or all these sources.Comment: published in Astronomy Report, translated by Yandex translator with correction of scientific lexis, 8 pages, 2 figures, 3 table

Knot homology via derived categories of coherent sheaves II, sl(m) case

Using derived categories of equivariant coherent sheaves we construct a knot homology theory which categorifies the quantum sl(m) knot polynomial. Our knot homology naturally satisfies the categorified MOY relations and is conjecturally isomorphic to Khovanov-Rozansky homology. Our construction is motivated by the geometric Satake correspondence and is related to Manolescu's by homological mirror symmetry.Comment: 51 pages, 9 figure

Associations of changes in lipid metabolism parameters and the severity of COVID-19 infection in Novosibirsk residents

Aim. To study the associations of changes in lipid metabolism parameters and the severity of a coronavirus disease 2019 (COVID-19).Material and methods. This cross-sectional study included 270 patients aged 26-84 years (mean age, 53,09±13,22 years) who had COVID-19 within prior two months, which were divided into 3 groups: mild (1, n=128), moderate (2, n=128) and severe (3, n=14) COVID-19. Patients were assessed for body mass index (BMI), waist circumference (WC), hip circumference (HC), waist-to-hip ratio (WHR), total cholesterol, triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C). In addition, atherogenic index of plasma (AIP) was calculated. Statistical processing was performed using the SPSS software package (version 13.0).Results. Patients with severe COVID-19 had significantly higher levels of TG and AIP compared with patients with moderate and mild course. BMI and WC were significantly higher in patients in groups 2 and 3 compared with patients in group 1. In women, BMI and AIP levels were significantly higher in the severe COVID-19 group compared to groups 1 and 2. HDL-C levels were lower in patients with severe COVID-19 compared to those with moderate disease. WHR was higher among men in group 3 compared with group 1.Conclusion. Patients with severe COVID-19 have higher BMI, WC, AIP, TG levels, and lower HD-C levels. The relative odds for severe COVID-19 are associated with increased WC, AIP, TG, and lower HDL-C

Non-alcoholic fatty liver disease and metabolic liver dysfunction in the new coronavirus infection COVID-19

Our study aimed to explore associated non-alcoholic fatty liver disease (NAFLD) and metabolic liver dysfunction influence on the severity of the new coronavirus infection COVID-19. Material and methods. The study design was a cross-sectional study. The research included 215 patients (39.50 % of men) aged 26–60 years who had undergone a new coronavirus infection COVID-19 at least two months ago. Participants were divided into three groups by severity of infection: mild (n = 99), moderate and severe (n = 116) by anamnesis. Hepatic steatosis index (HIS), body mass index (BMI), waist circumference, alanine aminotransferase and gamma-glutamyl transpeptidase activity, glucose and triglyceride content, systolic and diastolic pressure were calculated and abdominal ultrasound examination was done. Results. In the group with moderate and severe course of COVID-19, the proportion of patients diagnosed with NAFLDaccording to the HSI index was significantly higher compared to patients with mild coronavirus infection. Patients with mild COVID-19, who were diagnosed with NAFLD, had higher alanine aminotransferase and gamma-glutamyl transpeptidase activity, glucose and triglyceride content, BMI, systolic and diastolic pressure, waist circumference compared to patients without NAFLD. Similar differences persisted for patients with moderate and severe course. With the step-by-step exclusion of cardiometabolic parameters from the logistic regression model, the triglyceride content and BMI retained association with steatohepatosis according to ultrasound data, regardless of severity. When creating a similar model for the HSI index, significant correlation was shown for alanine aminotransferase activity in patients with mild COVID-19, for alanine aminotransferase activity and BMI – in patients with moderate and severe COVID-19. Conclusions. Patients with NAFLD have a more severe course of COVID-19. In addition, associations of the severity of COVID-19 with a combination of NAFLD and other cardiometabolic changes in the body, such as arterial hypertension, obesity, dyslipidemia, were revealed

Современные подходы к использованию глюкокортикоидных и цитотоксических препаратов при болезни Шегрена

Tsel' issledovaniya. Otsenit' effektivnost' dlitel'noy terapii bolezni Shegrena (BSh) malymi dozami glyukokortikoidnykh (GK) i alkiliruyushchikh tsitotoksicheskikh (ATs) preparatov Materialy i metody. V issledovanie vklyucheno 412 patsientov (406 zhenshchin i 6 muzhchin) s BSh, nablyudavshikhsya v Institute revmatologii v 1975 - 2007 gg. Mediana nablyudeniya - 9 (5-15) let. Sredniy vozrast bol'nykh na nachalo nablyudeniya - 44,8 goda. Mediana dlitel'nosti BSh do pervogo postupleniya - 9 let, mediana vozrasta debyuta BSh - 33 goda. Effektivnost' dlitel'noy terapii malymi dozami GKu 151 bol'nogo (mediana - 10 let), malymi dozami ATsu 147 bol'nykh (mediana - 5 let) otsenena v sravnenii s rezul'tatami lecheniya 94 bol'nykh, poluchavshikh tol'ko «oftal'mologicheskie» i «stomatologicheskie» metody terapii. Rezul'taty issledovaniya. Pokazano, chto terapiya malymi dozami GK i ATs polozhitel'no vliyala na nekotorye zhelezistye i vnezhelezistye proyavleniya zabolevaniya, odnako k snizheniyu veroyatnosti razvitiya limfoproliferativnykh zabolevaniy (r=0,036) i povysheniyu vyzhivaemosti bol'nykh s BSh privodila tol'ko terapiya ATs (r=0,037). Razrabotany i predstavleny metodiki lokal'nogo ispol'zovaniya GK pri tyazhelykh oftal'mologicheskikh i stomatologicheskikh proyavleniyakh BSh. U 150 bol'nykh s BSh s tyazhelymi sistemnymi proyavleniyami predstavleny pokazaniya i protivopokazaniya dlya provedeniya pul's-terapii (PT), kombinirovannoy PT, plazmafereza, krioafereza i dvoynoy fil'tratsii plazmy v sochetanii s kombinirovannoy PT. Pokazano, chto naznachenie malykh doz GK i PT u zhenshchin s BSh s sokhranennym menstrual'nym tsiklom privodit k bolee rannemu nastupleniyu menopauzy i sposobstvuet razvitiyu glyukokortikoidnogo i postmenopauzal'nogo osteoporoza v otdalennye sroki. Otseneny naibolee znachimye pobochnye proyavleniya terapii GK i ATs pri razlichnykh variantakh terapii BSh.Цель исследования. Оценить эффективность длительной терапии болезни Шегрена (БШ) малыми дозами глюкокортикоидных (ГК) и алкилирующих цитотоксических (АЦ) препаратов Материалы и методы. В исследование включено 412 пациентов (406 женщин и 6 мужчин) с БШ, наблюдавшихся в Институте ревматологии в 1975 - 2007 гг. Медиана наблюдения - 9 (5-15) лет. Средний возраст больных на начало наблюдения - 44,8 года. Медиана длительности БШ до первого поступления - 9 лет, медиана возраста дебюта БШ - 33 года. Эффективность длительной терапии малыми дозами ГКу 151 больного (медиана - 10 лет), малыми дозами АЦу 147 больных (медиана - 5 лет) оценена в сравнении с результатами лечения 94 больных, получавших только «офтальмологические» и «стоматологические» методы терапии. Результаты исследования. Показано, что терапия малыми дозами ГК и АЦ положительно влияла на некоторые железистые и внежелезистые проявления заболевания, однако к снижению вероятности развития лимфопролиферативных заболеваний (р=0,036) и повышению выживаемости больных с БШ приводила только терапия АЦ (р=0,037). Разработаны и представлены методики локального использования ГК при тяжелых офтальмологических и стоматологических проявлениях БШ. У 150 больных с БШ с тяжелыми системными проявлениями представлены показания и противопоказания для проведения пульс-терапии (ПТ), комбинированной ПТ, плазмафереза, криоафереза и двойной фильтрации плазмы в сочетании с комбинированной ПТ. Показано, что назначение малых доз ГК и ПТ у женщин с БШ с сохраненным менструальным циклом приводит к более раннему наступлению менопаузы и способствует развитию глюкокортикоидного и постменопаузального остеопороза в отдаленные сроки. Оценены наиболее значимые побочные проявления терапии ГК и АЦ при различных вариантах терапии БШ

Анализ эффективности цифровой реализации измерения параметров сигналов

The article reviews an algorithm of digital signal processing to implement computation of the amplitude of signal envelope, its frequency and initial phase. It also estimates performance accuracy reached owing to ideal model algorithm and its implementation. The practical implementation of the algorithm is part of the system exploring signal parameters.The goal was to test the algorithm capability to work in conditions of a priori uncertainty, having only input samples and measuring radio signal Gate [1], its capability to calculate the parameters of the radio signal with different modulation types while maintaining accuracy. Characterisation of radio signals is a very important process in radio engineering as having radio signal parameters can provide information about modulation radio signal and, consequently, information contained therein.Due to the high complexity of the algorithm, its mathematical description seems to be impossible, so construction of simulation models was chosen as a research tool. Practical implementation of the algorithm comprises a Hilbert transformer based on the FIR filter, a calculating unit of the amplitude envelope, a calculating unit of the phase detector signal, and a detector of the phase jumps. The article has discussed the algorithm in-detail and has shown deviations of values obtained in the practical implementation of the algorithm against the modeling ones. For the development and debugging of the algorithm programme, was created the Mathcad environment. The simulation results are also presented in the article.The running algorithm was tested under pulsed signal at the input, pulse signal at the FMmodulated input, and FM modulation noisy signal. Its accuracy is evaluated in comparison with the model. Dependence of envelope amplitude RMS versus dimensionality of the input signal was investigated as well. As a result, the optimum dimension of input signal was selected, as well as the accuracy of the algorithm in terms of a priori uncertainties was estimated.В статье рассмотрен алгоритм цифровой обработки сигналов, реализующий вычисление амплитуды огибающей сигнала, его частоты и начальной фазы, а так же была проведена оценка точности вычисленных характеристик. Практическая реализация алгоритма является частью системы, исследующей параметры сигнала. Целью работы было проверить способность алгоритма работать в условиях априорной неопределенности, имея на входе только отсчеты радиосигнала и измерительного строба [1]. Ввиду высокой сложности алгоритма, описание его математически не представляется возможным, поэтому в качестве аппарата для исследования было выбрано построение имитационной модели. В результате работы была исследована зависимость СКО амплитуды огибающей в зависимости от размерности входного сигнала, а так же оценена точность работы алгоритма в условиях априорной неопределенности. DOI: 10.7463/rdopt.0515.081296

Using CAST-test to investigate human specific hypersensitivity to the anthrax pathogen

We present the results of applying functional cytometric test of antigen-stimulated activation basophils to assess specific immunological reactivity in the people with anthrax, and immunized with anthrax vaccine. As a criterion for antigen-specific basophil activation, we measured expression of the CD63 membrane receptor, which reflects the process of anaphylactic basophil degranulation. To determine spontaneous and antigen-induced activation of basophils (CCR3+CD63+), a FlowCAST reagent kit (Buhlmann laboratories AG, Switzerland) was used. Anthraxin, an experimental anthrax allergen (a hydrolysate the Bacillus anthracis STI-1 strain), manufactured by the Stavropol Anti-Plague Institute, was used as a specific antigen. As based on clinical and experimental data, a threshold value of &gt; 10% of anthraxin-activated (CCR3+CD63+) basophils was accepted for the in vitro immunodiagnostic CAST test, as a laboratory criterion for the subjects exhibiting specific immune response, i.e., IgE-mediated sensitization. It was shown that, in anthrax patients within one week after onset of the disease (3-7 days), a positive CAST result was obtained in 92.3% cases; the levels of specific basophil activation with anthraxin averaged 37.9% (12.01 ÷ 78.9%). Immunological examination of individuals three weeks (21 days) after vaccination against anthrax revealed CAST-positivity in all the vaccinated persons. Intensity of anthraxin-induced basophil activation the vaccinated subjects was ranged from 10.87 to 30.03%, averaging 17.86%. The overall values of spontaneous and specific activation ranged within 12.39 ÷ 41.46%. The study opens prospectives for implementation of basophil antigenic activation test in the Flow CAST format in diagnostics of anthrax and to identify specific immune rearrangements after vaccination in humans, as an index of actual vaccination rates. Usage of CAST test with anthraxin makes it possible to identify anthrax patients at the early stages (2-4 days after onset of the disease) including, among patients with an increased CCR3+CD63+ background values, evaluation of immunological efficiency in the cohorts at risk for vaccination. At the same time, it was found that a significant decrease in diagnostic sensitivity of CAST test could be observed in the patients immune to anthrax pathogen who received intensive antibacterial and pathogenetic therapy at the early stages of infection, including glucocorticosteroids (anti-inflammatory drugs) and desensitizing agents that inhibit the degree of hypersensitivity development and its expression