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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Eliseeva NV, Ponomarenko IV, Churnosov MI

Primary open-angle glaucoma (POAG) is a complex disorder. Genetic factors play a vital part in POAG. The prevalence of POAG is gender-specific: the disorder is more often diagnosed in women. Results of the genome-wide association studies (GWAS) strongly support the association of CDKN2B-AS1 gene polymorphism with POAG. The aim was to perform the replicative study of CDKN2B-AS1 gene polymorphic loci association with POAG in women of the Central Black Earth Region, Russia. Five CDKN2B-AS1 gene single nucleotide polymorphisms (SNP), rs1063192, rs7865618, rs2157719, rs944800, and rs4977756, were genotyped in 290 female patients with POAG and 220 female controls. The differences in the haplotype block structure between the POAG patients (no haplotype blocks) and the controls (haplotype block consisting of three SNPs, rs1063192, rs7865618 and rs2157719, was detected) for the set of studied CDKN2B-AS1 SNPs were revealed using the Solid Spine algorithm (D’ > 0.8). CDKN2B-AS1 gene haplotype GGG rs1063192–rs7865618–rs2157719 is associated with POAG in women. This haplotype is considered a protective factor of the disorder (OR = 0.66; p = 0.006, рperm = 0.037).

Received: 2021-04-21

Published online: 2021-05-28

DOI: 10.24075/brsmu.2021.023

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Pankova OF, Kazin NM, Ivanova SM

The significance of studying the prevalence, age- and sex-related differences and diagnostic aspects of schizophrenia spectrum disorders (F2 Schizophrenia, schizotypal and delusional disorders) in pediatric and adolescent patients of mental health facilities is linked to the upcoming release of the International Classification of Diseases, Revision 11 (ICD-11). Its whole chapters have been updated, including disorders in the schizophrenia group. Diagnostic challenges posed by this debilitating group of mental disorders are associated with the diversity of clinical presentations, the incompleteness of psychopathological phenomena syndromes, and vague atypical symptoms. Changes in the prevalence of these disorders identified by the analysis of medical records at a mental health facility for children (a decline in the number of patients with F20, schizophrenia, and a surge in the number of patients with F21, schizotypal disorder) and significant disagreement about and disagreement about the diagnostic criteria for schizophrenia spectrum disorders in children and adolescents, evaluation of their dynamics, outcomes, and the social functioning of the patient necessitate further prospective follow-up studies aimed at overcoming the identified difficulties in the diagnosis, treatment and rehabilitation of such patients.

Received: 2021-03-31

Published online: 2021-05-20

DOI: 10.24075/brsmu.2021.022

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Knyazev EN, Paul SYu

In humans, trophoblast hypoxia during placental development can be a cause of serious pregnancy complications, such as preeclampsia and fetal growth restriction. The pathogenesis of these conditions is not fully clear and may be associated with changed expression of some genes and regulatory molecules, including miRNA, in trophoblast cells. The aim of this study was to analyze miRNA profiles and measure the expression of their target genes in a model of trophoblast hypoxia. Human choriocarcinoma BeWo b30 cells were used as a trophoblast model. Hypoxia was induced by cobalt chloride (CoCl2) and an oxyquinoline derivative. MRNA and miRNA expression profiles were evaluated by means of next generation sequencing (NGS); the expression of individual genes was analyzed by PCR. We studied the secondary structure of mRNAs of target genes for those miRNAs whose expression had changed significantly and analyzed potential competition between these miRNAs for the binding site. The observed changes in the expression of the key genes involved in the response to hypoxia confirmed the feasibility of using CoCl2 and the oxyquinoline derivative as hypoxia inducers. The analysis revealed an increase in miR-374 levels following the activation of the hypoxia pathway in our trophoblast model. The changes were accompanied by a reduction in FOXM1 mRNA expression; this mRNA is a target for hsa-miR-374a-5p and hsa-miR374b-5p, which can compete with hsa-miR-21-5p for the binding sites on FOXM1 mRNA. The involvement of FOXM1 in the regulation of the invasive cell potential suggests the role of miR-374 and FOXM1 in the pathogenesis of disrupted trophoblast invasion during placental development as predisposing for fetal growth restriction and preeclampsia.

Received: 2021-04-20

Published online: 2021-04-30

DOI: 10.24075/brsmu.2021.021

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Nizyaeva NV, Lomova NA, Dolgopolova EL, Petrova UL, Karapetyan TE, Shmakov RG, Frankevich VE

Impaired placental development during early pregnancy associated with systemic damage to the vascular endothelium in patients with COVID-19 may result in a number of complications. The study was aimed to reveal histological and immunohistochemical (IHC) features of placental tissue in pregnant women with COVID-19 at different stages of gestation, and to examine the contribution of those to pathogenesis of the disease involving mother-placenta-fetus system. The following two groups of pregnant women were studied: index group of 66 patients with COVID-19, and comparison group of 40 women with no symptoms of viral infection. Macroscopic and microscopic examination, and the IHC analysis of placental samples were carried out. Clinical and anamnestic characteristics of patients with COVID-19 were analyzed taking into account disease severity, delivery route and perinatal outcome. ICH staining using primary antibody revealed elevated expression of proinflammatory factors (TNFα, IL8) and reduced level of anti-inflammatory factors (IL4) in placental structures of patients with moderate and severe СOVID-19 (р < 0.05). The villous tree rearrangement and the development of subclinical placental insufficiency, which could in some cases be decompensated during labor, resulting in clinical manifestations of acute fetal hypoxia were detected in the placental samples obtained from the index group patients. The obstetrical tactics for mothers with COVID-19 should be decided individually based on the risk factors; continuous cardiotocography should be used during labor. It may be appropriate to conduct IHC analysis of placenta in puerperant women with COVID-19 in order to fine-tune the tactics of neonatal management and to predict possible neonatal complications.

Received: 2021-04-14

Published online: 2021-04-30

DOI: 10.24075/brsmu.2021.020

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Milushkina OYu, Zhukov OF, Lukanova OV, Markelova SV, Skoblina NA

Distance learning (DL) changed the work-rest balance of teachers, increased risks of deterioration of their health and emotional burnout (EB). This study aimed to investigate the prevalence of risk factors affecting health and emotional state of teachers engaged in DL, as well as subjective assessment of the significance of these factors by teachers. We have surveyed teachers during traditional, in-person learning (TL) period (n = 224) and DL (n = 619), and took anthropometric measurements of 45 teachers during TL and 72 teachers when DL ended. EB was studied in 72 teachers with the help of V.V. Boyko questionnaire. Statistical processing was enabled by the Statistica 13 PL package, Student's t-test, χ2 test; to identify the relationship between indicators, we relied on regression analysis, effect occurrence probability calculation. Less than half of teachers are aware of the health risk factors (low level of physical activity — 36.1%, poor nutrition — 29.2%, lack of knowledge on disease prevention — 6.9%). After DL ended, only 30% of teachers considered themselves healthy; 13.1% reported lack of EB symptoms. An increase in the average body mass index value was established. Teachers underestimating EB and health risk factors were 2.3 times more likely to grow obese (OR = 0.40; 95% CI = 0.22–0.70). The study highlights high hygienic value of physical activity as a controllable health risk factor. Raising teachers' awareness of health preservation practices will help prevent deterioration of their health, development of EB and increase the efficiency of their professional activity.

Received: 2021-03-19

Published online: 2021-04-29

DOI: 10.24075/brsmu.2021.019

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Gerasimova AA, Klimenko PA

The problem of ovarian tumor differential diagnosis is solved using comprehensive ultrasound examination at different levels of efficiency. However, ultrasound imaging is an operator-dependent technique due to subjective interpretation of results. The study was aimed to assess the ultrasound signs of benign and malignant ovarian germ cell tumors (OGCTs) in pregnant women in order to determine the feasibility of surgical treatment and chemotherapy. The study was carried out using the logistic regression models. A group of 199 pregnant women with benign and malignant OGCTs were enrolled. Of them, 183 patients had benign, and nine patients had malignant tumors. In order to assess menstrual function and fertility, seven pregnant women were enrolled, who had previously received treatment for malignant OGCTs. Pre-operative assessment results were compared with morphological assessment data. Organ-preserving surgical treatment was performed (unilateral adnexectomy); if necessary, the patients received cisplatin-based chemotherapy. Perinatal outcomes were assessed. The median observation time between the malignant OGCT detection and the end of the study was 66 months (12–240 months). It was found that comprehensive ultrasound examination and logistic regression models (sensitivity 100%, specificity 92.3%, overall accuracy 92.8%) enabled differential diagnosis of benign and malignant OGCTs. The number of unnecessary surgical procedures in patients with benign OGCTs was been limited, the pregnancy and childbirth outcomes were improved. Nine pregnant women received organ-preserving surgical treatment for malignant OGCTs, and three patients received chemotherapy after surgery, which allowed the patients to realize their reproductive potential.

Received: 2021-03-15

Published online: 2021-04-28

DOI: 10.24075/brsmu.2021.018

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VIEWS 3449

Kopetskiy IS, Meskhiya NG, Kopetskaya AI, Eremin DA, Orekhova DD

Changing the vestibulo-oral inclination (torque) of the frontal teeth is an important component of orthodontic treatment. Cone-beam computed tomography is recommended as an accurate diagnostic tool allowing the orthodontist to estimate the safety of frontal tooth movement and inclination. This tool is helpful in measuring bone thickness at different levels of the tooth root and estimating incisal inclination and position. The aim of our study was to analyze bone thickness in patients with pathologically and normally inclined teeth using CT images and to create a universal table that will provide useful information about the thickness of the bone around different segment of the root required for a safe change in tooth inclination. Using the proposed table, the orthodontist can assess the feasibility of the planned tooth movement in the setting of changed tooth inclination, with due account of critical bone deficit regions. This will ensure the safety of tooth movement, stable retention and a positive treatment outcome.

Received: 2021-03-16

Published online: 2021-04-27

DOI: 10.24075/brsmu.2021.015

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VIEWS 3365

Masyutina AA, Gumenyuk LN, Fatovenko YuV, Sorokina LE, Bayramova SS, Alekseenko AI, Shavrov YuV, Romanova AA, Seydametova DI

The relationship between the gut microbiota and chronic insomnia remains understudied. The aim of this paper was to investigate changes in the taxonomic composition of the gut microbiota and their associations with the levels of cortisol, melatonin and IL6 in patients with chronic insomnia. Our comparative prospective cross-sectional study enrolled 55 patients with chronic insomnia, who formed the main group (female patients: 58.2%, male patients: 41.8%; mean age 31.6 ± 7.4 years), and 50 healthy volunteers, who comprised the control group (females: 68.0%, males: 32.0%; mean age 33.2 ± 6.6 years). The taxonomic composition of the gut microbiota was profiled using 16S rRNA gene sequencing. Plasma cortisol and IL 6 and urine melatonin were measured by means of ELISA. Sleep quality was evaluated using the Pittsburgh Sleep Quality Index (PSQI). In patients with chronic insomnia, the abundance of Faecalibacterium (p = 0.048), Prevotella 9 (p < 0.001) and Lachnospira (p = 0.036) was lower, whereas the abundance of Blautia (p = 0.012) and Eubacteriumhallii (p = 0.003) was higher than in healthy volunteers. Significant correlations were established between the levels of IL6 and the abundance of Faecalibacterium (r = –0.44; p = 0.001) and Blautia (r = 0.42; p < 0.001), as well as between cortisol concentrations and the abundance of Lachnospira (r = –0.41; p = 0.048). The abundance of Faecalibacterium and Blautiaс was correlated with higher PSQI (r = –0.47, p = 0.001; r = 0.45, p < 0.001, respectively). Our study contributed to the pool of data about changes in the gut microbiota and their associations with some endocrine and inflammation markers in patients with chronic insomnia. These data can be exploited to propose new strategies for the diagnosis and personalized treatment of insomnia aimed at normalizing the patient’s gut microbiota.

Received: 2021-03-07

Published online: 2021-04-27

DOI: 10.24075/brsmu.2021.017

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VIEWS 4050