Bulletin of RSMU

ISSN Print 2500–1094 ISSN Online 2542–1204

Bulletin of RSMU

BIOMEDICAL JOURNAL OF PIROGOV UNIVERSITY (MOSCOW, RUSSIA)

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Traspov AA, Minashkin MM, Poyarkov SV, Komarov AG, Shtinova IA, Speshilov GI, Karbyshev IA, Pozdniakova NV, Godkov MA

Both genetic and non-genetic factors are responsible for high interindividual variability in response to SARS-CoV-2. Despite the fact that multiple genetic polymorphisms have been identified as risk factors of severe COVID-19, such polymorphisms are still insufficiently studied in the Russian population. The study was aimed to identify genetic determinants associated with severe COVID-19 in the sample of patients from the Russian Federation. The correlation of the rs17713054 polymorphism in gene LZTFL1 and rs1800629 polymorphism in gene TNF (tumor necrosis factor) with the COVID-19 severity was assessed. DNA samples obtained from 713 patients (324 males and 389 females) aged 18‒95 with COVID-19 of varying severity were analyzed. The rs1800629 polymorphism of gene TNF (OR = 1.5; p = 0.02) and rs17713054 polymorphism of gene LZTFL1 (OR = 1.60; p = 0.0043) were identified as risk factors of severe disease. The TNF polymorphism rs1800629 and LZTFL1 polymorphism rs17713054 could be considered as potential predictive biomarkers. The rs17713054 G > A polymorphism was strongly associated with severe disease. In the future the findings may provide the basis for the development of test-systems for prediction of the risk of severe viral respiratory diseases.

Received: 2022-11-18

Published online: 2022-12-28

DOI: 10.24075/brsmu.2022.065

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VIEWS 1193

Ibragimova RR, Gilmanov II, Lopukhova EA, Lakman IA, Bilyalov AR, Mukhamadeev TR, Kutluyarov RV, Idrisova GM

Age-related macular degeneration (AMD) is one of the main causes of loss of sight and hypovision in people over working age. Results of optical coherence tomography (OCT) are essential for diagnostics of the disease. Developing the recommendation system to analyze OCT images will reduce the time to process visual data and decrease the probability of errors while working as a doctor. The purpose of the study was to develop an algorithm of segmentation to analyze the results of macular OCT in patients with AMD. It allows to provide a correct prediction of an AMD stage based on the form of discovered pathologies. A program has been developed in the Python programming language using the Pytorch and TensorFlow libraries. Its quality was estimated using OCT macular images of 51 patients with early, intermediate, late AMD. A segmentation algorithm of OCT images was developed based on convolutional neural network. UNet network was selected as architecture of high-accuracy neural net. The neural net is trained on macular OCT images of 125 patients (197 eyes). The author algorithm displayed 98.1% of properly segmented areas on OCT images, which are the most essential for diagnostics and determination of an AMD stage. Weighted sensitivity and specificity of AMD stage classifier amounted to 83.8% and 84.9% respectively. The developed algorithm is promising as a recommendation system that implements the AMD classification based on data that promote taking decisions regarding the treatment strategy.

Received: 2022-11-03

Published online: 2022-12-27

DOI: 10.24075/brsmu.2022.062

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VIEWS 1255

Porosyuk MV, Klementiev DD, Hodov NA, Gumenyuk LN, Esatova ES, Sereda EV, Chetveruhina-Malova KS, Sarchuk EV, Ivanov SV

Currently, the issue of the relationship between gut microbiota and juvenile idiopathic arthritis (JIA) is still relevant. The study was aimed to assess alterations in the gut microbiota taxonomic composition and estimate the relationship between these alterations and cortisol, melatonin, and TNFα at the genus level in patients with JIA. The comparative cross-sectional study involved 65 patients with JIA (index group) and 60 healthy children (control group). The gut microbiota taxonomic composition and plasma levels of cortisol, melatonin, and TNFα were assessed. The following alterations of the gut microbiota taxonomic composition were found in patients with JIA: the significantly decreased abundance of Anaerostipes (р = 0.042), Lachnospira (р = 0.034), Roseburia (р = 0.002), Coprococcus (р = 0.014), Dialister (р = 0.003) and the increase in the abundance of Ruminococcus (р = 0.012). There were significant correlations of cortisol levels with the abundance of Lachnospira (r = –0.44; p = 0.001), melatonin concentrations and the abundance of Coprococcus (r = –0.48; p = 0.023), the levels of TNFα and the abundance of Ruminococcus (r = 0.52; p = 0.001). The association of the Lachnospira, Roseburia, and Ruminococcus abundance with the higher DAS28 scores was discovered (r = –0.57; p = 0.002; r = –0.44; p = 0.002; r = 0.54; p = 0.032, respectively). The findings provide additional information about the features of gut microbiota alterations and their correlation with some hormone and inflammatory biomarkers associated with JIA, that could provide the basis for further research and possibly for new approaches to treatment of this disorder.

Received: 2022-11-01

Published online: 2022-12-19

DOI: 10.24075/brsmu.2022.060

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VIEWS 1073

Gospodaryk AV, Ulakhanova LA, Esiev SS, Polyakova EV, Shansky YD, Bespyatykh JA

Fecal microbiota transplantation (FMT) is prescribed to treat various gastrointestinal pathologies. One of the most important and significant stages of FMT is selection of the donor. In recent years, special attention has been paid to checking the biomaterial for genes marking resistance to various groups of antibiotics. This study aimed to analyze the occurrence of mef and ermB drug resistance genetic markers in population of various age groups, including breastfed infants, and to determine microbiological composition of the flora of distal part of the intestine of potentially healthy volunteering FMT donors. A total of 52 biological samples (46 stool samples and 6 breast milk samples) were analyzed by real-time polymerase chain reaction. The macrolides resistance gene (mef) was detected in 97.8% of stool samples (different age groups), the gene marking resistance to macrolides, lincosamides, streptogramin (ermB) — in 93.5%. In the isolated "mother-child" group, the mef gene was found in all samples of breast milk and feces. The ermB gene in this group was found in 3 out of 6 breast milk samples and 4 out of 6 infant stool samples. Since the mef and ermB genetic determinants were identified not only among in adults but also in infants, it was suggested that transplant material (feces) containing these genes can be used for FMT. The analysis of microbiological composition of stool samples from 23 healthy volunteers (potential FMT donors) revealed that it rarely (in 8.7% of cases only) corresponds to what is considered to be a normal microbiota of the intestine's distal part.

Received: 2022-10-20

Published online: 2022-12-16

DOI: 10.24075/brsmu.2022.059

Comments 1

VIEWS 1219

Orlova EV, Berdalin AB, Lelyuk VG

Identification of the age-related features of interaction between the risk factors of microembolism can improve understanding of the mechanisms underlying the development of ischemic stroke (IS). The study was aimed to assess the effects of age and other risk factors of stroke on the biophysical characteristics of microembolic signals (MES) recorded during the ischemic stroke recovery period. Transcranial Doppler ultrasound (TCD) involving microembolus detection (MED) was performed in 515 people, the data of 28 patients having a history of ischemic stroke, among them 9 women (32%) and 19 men (68%) aged 33–78 (average age 58 ± 13 years), were included in the study. Using the mixed-effects linear model it was found that age and interaction between age and atrial fibrillation affected the power of MES. The increase in the power of the recorded MES with age is observed, that is especially evident in patients with atrial fibrillation (р < 0.0005). As for cardioembolic IS variant, the power and duration of MES turn out to be significantly higher in elderly patients (p < 0.0005). The power of MES gradually increases with age in patients with no atherosclerosis and gradually decreases in patients with atherosclerosis, while MES power in patients with atherosclerosis in general (all age groups) is significantly higher (р < 0.0005) than that observed in patients with no atherosclerosis.

Received: 2022-10-28

Published online: 2022-12-12

DOI: 10.24075/brsmu.2022.058

Comments 0

VIEWS 1072

Salmasi JM, Poryadin GV, Panina MI, Larina VN, Ryzhikh AA, Stodelova EA, Kazimirskii AN

Post-COVID syndrome (long covid, post COVID-19 condition) is characterized by cognitive and mental disorders, chest and joint pain, impaired sense of smell and taste, as well as by gastrointestinal and cardiac disorders. The diagnosis of post-COVID syndrome is based mainly on the patients' complaints. To date, no optimal diagnostic method has been proposed. The study was aimed to compare the informative value of the indicators obtained during conventional assessment of patients with post-COVID syndrome and the blood levels of neutrophil (NETs) and monocyte (METs) extracellular traps. The study involved neutropils and monocytes collected from 21 patients with post-COVID syndrome aged 18–59. Fluorescence microscopy and the SYBR Green (Evrogen) fluorescent dye for double-stranded DNA were used for enumeration and imaging of extracellular traps. Clinical and laboratory indicators make it impossible to identify the changes specific for post-COVID syndrome. At the same time, post-COVID syndrome is characterized by inflammation in the vascular endothelium. The filamentous forms of NETs found in blood are a laboratory feature of such aseptic inflammation. The filamentous forms of NETs have been detected only in those patients who have a history of mild to severe СOVID-19, while the filamentous forms of METs have been found in patients having a history of severe infection. The findings show that the detection of the filamentous forms of NETs and METs in blood is the most informative diagnostic feature of post-COVID syndrome.

Received: 2022-10-29

Published online: 2022-12-09

DOI: 10.24075/brsmu.2022.057

Comments 0

VIEWS 1619

Kalinkin AI, Sigin VO, Nemtsova MV, Strelnikov VV

Breast cancer (BC) is the most frequently diagnosed cancer and one of the major causes of female mortality. The development of prognostic models based on multiomics data is the main goal of precision oncology. Aberrant DNA methylation in BC is a diagnostic marker of carcinogenesis. Despite the existing factors of BC prognosis, introduction of methylation markers would make it possible to obtain more accurate prognostic scores. The study was aimed to assess DNA methylation signatures in various BC subtypes for clinical endpoints and patients' clinicopathological characteristics. The data on methylation of CpG dinucleotides (probes) and clinical characteristics of BC samples were obtained from The Cancer Genome Atlas Breast Cancer database. CpG dinucleotides associated with the selected endpoints were chosen by univariate Cox regression method. The LASSO method was used to search for stable probes, while further signature construction and testing of the clinical characteristics independence were performed using multivariate Cox regression. The dignostic and prognostic potential of the signatures was assessed using ROC analysis and Kaplan–Meier curves. It has been shown that the signatures of selected probes have a significant diagnostic (AUC 0.76–1) and prognostic (p < 0.05) potential. This approach has made it possible to identify 47 genes associated with good and poor prognosis, among these five genes have been described earlier. If the genome-wide DNA analysis results are available, the research approach applied can be used to study molecular pathogenesis of BC and other disorders.

Received: 2022-10-18

Published online: 2022-11-25

DOI: 10.24075/brsmu.2022.056

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VIEWS 1165

Andreevskaya SN, Smirnova TG, Chernousova LN, Larionova EE, Kiseleva EA, Ergeshov A

Fluoroquinolones are the main group of drugs used for treatment of multidrug resistant tuberculosis (MDR-TB). The study was aimed to assess the diversity of mutation in the gyrA gene and to evaluate the association of gyrA mutations with the phenotypic resistance to levofloxacin and the general drug resistance profile of the pathogen. The study involved assessment of diagnostic materials obtained from 2836 patients with pulmonary tuberculosis. TB-BIOCHIP-2 and AmplitubeFQ-RV kits were used for identification of the gyrA mutations. Phenotypic drug susceptibility of M. tuberculosis (MTB) was defined using the BACTEC MGIT 960 test system. It was shown that mutations D94G (41.63%; 95% CI: 38.03–45.32%) and A90V (21.32%; 95% CI: 18.44–24.50%) prevailed in MBT, although some isolates carrying these mutations were obtained from the newly diagnosed patients with pulmonary tuberculosis. It was found that mutation D94A was not strongly associated with the phenotypic resistance to fluoroquinolones. Fluoroquinolone resistance was usually associated with multiple drug resistance (93.52%; 95% CI 91.43–95.12%). In 2.31% (95% CI 1.78–3.00%) of cases, genotypic heteroresistance to fluoroquinolones was detected: mixed populations included 2–4 MTB pools with various structure of the gyrA QRDR. The results obtained lead to the conclusion that resistance to fluoroquinolones that is usually associated with the existing MDR arises in the modern MTB population. MTB carrying gyrA mutations D94G and A90V seems to be the most promising in evolutionary terms.

Received: 2022-10-10

Published online: 2022-10-31

DOI: 10.24075/brsmu.2022.054

Comments 0

VIEWS 1142