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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Poydasheva AG, Sinitsyn DO, Bakulin IS, Suponeva NA, Piradov MA

Repetitive transcranial magnetic stimulation (rTMS) is an alternative treatment option for patients with drug-resistant trigeminal neuralgia (TN). However, the effect of rTMS is variable. The aim of this study was to find neuroimaging biomarkers of clinical efficacy of navigated rTMS. Seventeen patients with TN (14 women and 3 men, median age 56 years) received 10 sessions of high-frequency rTMS of the motor cortex contralateral to pain side. The data were analyzed for correlations between functional connectivity (FC), the grey matter (GM) volume and the reduction in pain intensity. Positive correlations were established between the reduction in average pain intensity and GM volume in caudate nuclei in both hemispheres (p(unc) = 0.03), both cerebellar hemispheres (p(unc) = 0.002) and the postcentral gyrus contralateral to pain side (p(unc) = 0.005); between the reduction in peak pain intensity and GM volume in the caudate nucleus contralateral to pain side (p(unc) = 0.04) and the cerebellar hemisphere ipsilateral to pain (p(unc) = 0.03). Significant positive correlations were discovered between the reduction in average pain intensity and FC between the thalamus contralateral to pain side, the postcentral gyrus and the insular operculum (both ipsilateral to pain side; (p(FWE) = 0.018), as well as between the cingulate cortex and the anterior cingulate cortex ipsilateral to pain (p(FWE) = 0.017), between the contralateral subcallosal gyrus and the cerebellar hemisphere ipsilateral to pain (p(FWE) = 0.018). A negative correlation was established for FC between the contralateral putamen and the occipital lobes in both hemispheres (p(FWE) = 0.001). Our findings may spur the development of individual predictors of rTMS efficacy in patients with chronic pain.

Received: 2021-05-18

Published online: 2021-06-12

DOI: 10.24075/brsmu.2021.027

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VIEWS 2021

Radaeva OA, Simbirtsev AS, Kostina YuA, Iskandiarova MS, Mashnina SV, Bessheynov DD, Negodnova EV, Kulyapkin VV

Pathogenetic progression mechanisms in the SARS-CoV-2–essential hypertension (EAH) system are more complex than interaction at the level of angiotensinconverting enzyme 2 (ACE2). The study was aimed to assess the dynamic changes of the IL1 members (IL1β, IL1α, IL1ra, IL18, IL18BP, IL37) blood levels in patients with EAH 10, 30, and 180 days after having COVID-19 in order to define cytokine-mediated mechanisms of EAH progression during the period following infection. The study involved four groups of patients: with a history of EAH and COVID-19 (pneumonia/no pneumonia), with a history of COVID-19 (pneumonia/no pneumonia) and no EAH. Cytokine levels were determined by enzyme immunoassay. The study results demonstrate the prolonged proinflammatory immune response during the period following infection in patients with EAH (retaining higher levels of IL1β, IL1α, and IL18 on days 10, 30, and 180 after recovery (р < 0.001) compared to levels measured prior to SARS-CoV-2 infection). In the group with no EAH, the balance of assayed cytokines was restored on day 30 of follow-up. The two-fold increase of blood IL18 levels in patients, having a history of EAH and COVID-19 and showing no increase in the IL18ВР levels after 30 days of follow up compared to the values measured prior to infection, is associated with cardiovascular complications occurring during the first six months of follow-up. This makes it possible to hypothesize the importance of these immunoregulatory peptides for the pathogenesis of complications and enhances the relevance of further scientific research.

Received: 2021-05-19

Published online: 2021-06-07

DOI: 10.24075/brsmu.2021.026

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VIEWS 2402

Reshetnikov MN, Plotkin DV, Zuban ON, Bogorodskaya EM

The double burden of the novel coronavirus infection and tuberculosis (TB) is a global challenge. The aspects of emergency surgical care for patients with COVID-19 and TB coinfection remain understudied. The aim of this study was to assess treatment outcomes in acute surgical patients with COVID-19 and preexisting TB coinfection. In 2020, our Center delivered surgical care to 465 patients with COVID-19 and preexisting TB; a total of 64 emergency surgeries were performed on 36 (5.6%) patients, of whom 16 had HIV. Thirteen patients (36.1%) were diagnosed with pulmonary TB; 23 patients (63.9%) had disseminated TB. Chest CT scans showed >25% lung involvement in 61.9% of the patients with COVID-19 pneumonia, 25–50% lung involvement in 30.6% of the patients, and 50–75% lung involvement in 5.6% of the patients. By performing abdominal CT, we were able to detect abdominal TB complications, including perforated tuberculous ulcers of the intestine, intestinal obstruction and tuberculous peritonitis, as well as tuberculous spondylitis complicated by psoas abscess. Of all surgical interventions, 28.2% were abdominal, 23.2% were thoracic, 15.6% were surgeries for soft tissue infection, and 32.8% were other types of surgery. Postoperative mortality was 22.2%. We conclude that COVID-19 did not contribute significantly to postoperative mortality among acute surgical patients with TB.

Received: 2021-04-12

Published online: 2021-05-31

DOI: 10.24075/brsmu.2021.025

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VIEWS 2056

Shcheglov AS, Tsarkova AS

Ferroptosis is a form of programmed cell death associated with iron-dependent lipid peroxidation. Novel ferroptosis inducers and suppressors could be instrumental in developing drugs against neurodegenerative disorders and cancer. Prior to embarking on a search for ferroptosis inducers/suppressors, this form of cell death must be studied in living cells and laboratory animals. In addition to two cofactors, luciferase (or photoprotein) of the parchment tubeworm Chaetopterus variopedatus requires the presence of iron ions and hydrogen peroxide or organic hydroperoxides to exert its activity. Therefore, the bioluminescence system of the parchment tubeworm can be used to study ferroptosis in living organisms.

Received: 2021-05-05

Published online: 2021-05-30

DOI: 10.24075/brsmu.2021.024

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VIEWS 1920

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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VIEWS 1893

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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VIEWS 2184

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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VIEWS 2274

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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VIEWS 2444