ISSN Print 2500–1094    ISSN Online 2542–1204
BIOMEDICAL JOURNAL OF PIROGOV UNIVERSITY (MOSCOW, RUSSIA)

New articles

The cerebral circulatory disorder associated with arterial hypertension results in neuroinflammation, in which microglia and macrophages of the brain are actively involved. The study aimed to assess functional activity and immunophenotype of microglia and macrophages in the areas of brain barriers in spontaneously hypertensive rats (SHR). Specimens of the brain of male Wistar and SHR rats (age 3–4 months, n = 10) were used. The study involved the use of immunohistochemistry analysis and confocal laser microscopy. The presence of М2 activation (CD206) and phagocytic activity (CD68) markers in the population of microglia and macrophages was assessed. It was shown that the CD206 protein was present in perivascular cells, the counts of which were considerably increased in SHR rats (40.69 ± 4.87 cells per 1 mm2 vs. 28.73 ± 1.39 in Wistar rats; t-test, р = 0.0007). The quantitative analysis conducted allowed us to identify the upward trend of the share of phagocytic cells in the brain of SHR rats compared to Wistar rats. No changes in the CD68 protein distribution were found in SHR rats, therefore, activation of microglia and macrophages is not accompanied by the phagocytic activity increase. The findings suggest alternative activation of brain macrophages in neuroinflammation caused by arterial hypertension.
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Assessment of phantom pain linguosemantic descriptors in patients with traumatic amputation during the use of mirror visual feedback is conditioned by the need to find criteria for the psychological phantom pain adjustment effectiveness. The study aimed to assess the dynamic changes in linguosemantic pain descriptors in patients with traumatic amputation showing manifestations of phantom pain syndrome as a criterion for evaluating the effectiveness of mirror visual feedback. The total sample size was 87 males post traumatic amputation of one lower limb (age 23–55 years). The research methods were as follows: Mini Mental State Examination (MMSE), original form for registering linguosemantic descriptors of phantom painful sensations, Visual Analog Scale (VAS) for phantom pain. The detected dynamic changes in linguosemantic descriptors of phantom painful sensations in patients with traumatic amputation of the limb showing manifestations of phantom pain syndrome during treatment involving the use of mirror visual feedback makes it possible to consider the following as effectiveness criteria: an increase in the number of pain descriptors represented mainly by concrete and tangible nouns (makes it possible to reduce phantom pain severity rated using a 10-point scale), as well as the increase in the number of descriptors that characterize non-painful unpleasant sensations at the linguosemantic level.
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Tortuosity of the coronary, cerebral arteries, aorta and its branches remains an important vascular problem, which, on the one hand, complicates selection of the X-ray surgical treatment tactics, and on the other hand worsens the disease outcome. The lack of common standards for assessment of tortuosity of the coronary, cerebral arteries, aorta and its branches reduces the diagnosis accuracy in patients at high risk of cardiovascular events. The use of machine learning for automated tortuosity assessment represents one possible solution to this problem. The study aimed to analyze and compare accuracy, feasibility, and limitations of the available methods for automated assessment of tortuosity of the coronary, cerebral arteries, aorta and its branches using the machine learning tools. The systematic review was conducted in accordance with the PRISMA protocol. The search for papers published in 2015–2025 in the PubMed, Scopus, and eLibrary databases was performed using the following keywords: deep learning, machine learning, artificial intelligence, vessel tortuosity, curvature. Six papers out of 240 were included in the analysis. The analysis has shown that 80% of approaches are based on convolutional neural networks, and skeletonization aimed to isolate small blood vessels from the artery represents an essential preprocessing phase. In 50% of papers, tortuosity was determined qualitatively based on the presence of bending angles over 45°. Quantitatively, tortuosity was determined as a distance coefficient and a measure of curvature. In three studies out of six, verification of estimates was carried out by comparing the results with expert opinions (accuracy was 0.92–0.94). The study limitations are as follows: monocentricity, the use of data from one type of equipment.
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High efficacy of the synthetic Ac-His-Ala-Glu-Glu-NH2 (HAEE) peptide in suppression of the congophilic amyloid plaque formation was earlier shown in the animal model of Alzheimer's disease. The study conducted as part of the pre-clinical trial aimed to determine the optimal therapeutic dose of this peptide when used as an anti-amyloid agent for treatment of this disorder. The APP/PS1 transgenic mice randomized into four experimental groups and one control group (eight males and eight females per group) were used as model animals. Mice of experimental groups 1, 2, 3, and 4 twice a week throughout eight weeks received subcutaneous injections of drugs with the following HAEE dosage: 0.18 mg/kg, 0.30 mg/kg, 1.50 mg/kg, 3.00 mg/kg. Mice of the control group were administered saline. The Congo red stain was used to determine amyloid plaques in the hippocampus of all animals. Quantification of such plaques showed a significant (p < 0.001) decrease in the number of plaques in mice of experimental groups (the average plaque number per brain slice was 7.5 ± 2.1, 3.2 ± 0.9, 3.1 ± 0.6, and 3.3 ± 0.7 in mice of groups 1, 2, 3, and 4, respectively) compared to control mice (15.7 ± 4.6). Since the number of plaques in groups 2, 3, and 4 did not change significantly, the minimal HAEE dose, with which the lowest number of amyloid plaques is observed in the studied mice, is 0.3 mg/kg. This is roughly equivalent to the dose of 1.75 mg in terms of one adult human. Thus, the optimal therapeutic HAEE dose for clinical trials has been experimentally substantiated.
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Popular articles

Accumulation of senescent cells in the tissues is associated with functional impairment and the development of age-related disorders. The key role in this process is played by the senescence-associated secretory phenotype (SASP) contributing to chronic systemic inflammation, which is associated with the increased risk of autoimmune disorders and cancer, as well as the decreased resistance to infections. Normally, the immune system eliminates senescent cells, but the effectiveness of this process decreases with age, including due to the immune system aging. The study aimed to assess age-related alterations in the main lymphocyte and myelocyte populations in the spleen and bone marrow samples of senile mice. The study involved groups of young (n = 8) and elderly (n = 4) С57BL/6 mice. Populations were tested by flow cytometry using the fluorescence-labeled antibodies. The aging phenotype was assessed based on the β-Gal enzyme activity with pre-treatment with bafilomycin А1, ensuring lysosomal alkalinization and allowing one to detect the increased enzyme activity typical for the aging cells (SA-β-Gal). As a result, the significantly increased levels of myeloid populations, CD11c+ B cells, double-negative T cells, along with the decreased levels of the CD8α+ dendritic cells, were reported in elderly mice. Furthermore, aging was associated with the significant increase in the levels of SA-β-Gal-positive cells, especially in the populations of myeloid cells. The data obtained suggest that the age-related alterations are of systemic nature and reflect the so-called myeloid shift, as well as accumulation of pro-inflammatory populations in the myeloid and lymphoid compartments.
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High-grade non-anaplastic (HGFC-NA) thyroid tumors belong to a rare and aggressive category of neoplasms that occupy an intermediate position between differentiated and anaplastic carcinomas. There are high mortality rate and limited standard treatment options, which usually include surgical tumor removal with subsequent radioiodine treatment and levothyroxine suppression therapy. Targeted tyrosine kinase inhibitors are additionally considered in radioiodineresistant forms, but the efficacy of those is limited. A clinical case of differentiated high-grade thyroid carcinoma (DHGTC) in a 62-year-old female patient post hemithyroidectomy is presented. Histological assessment, immunohistochemistry (TTF-1, PAX8, CK19, p53, Ki-67), and the key marker (TERT, TP53, BRAF) molecular testing methods were used. The tumor size was 3.4 × 2.8 × 2.5 cm; the tumor showed pronounced architectonic heterogeneity, focal necrosis, high mitotic activity — 8–10 mitoses per 10 fields of view at ×400 (corresponding to ≥ 5 per 2 mm2), and the Ki-67 proliferation index reached 35%. IHC was used to detect the TTF-1 and PAX8 expression, mutational p53 pattern of expression, suggesting the TP53 mutation. Molecular testing revealed no alteration of the TERT and BRAF genes. These characteristics made it possible to verify the diagnosis of DHGTC. A conclusion was drawn about the need for comprehensive morphological and molecular diagnosis of HGFC-NA tumors, since the mitotic activity quantitative parameters, Ki-67, and TERT/TP53 status determine the prognosis and the personalized therapy selection.
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Dear researcher!
At the end of 2015, Bulletin of RSMU saw an important change in its typographic design and content. We formulated new editorial policies and established strict ethical standards for submitted manuscripts in accordance with the guidelines of reputable international bodies. As a result, about a quarter of the submitted works have been rejected, the primary reason being the author trying to submit a previously published article. Sometimes authors believe that by making slight changes to the introduction, excluding a few people from the study, performing a new statistical analysis, and thus obtaining totally new results they will turn their old manuscript into a novel work. That is why we would like to talk about scientific integrity, honesty, plagiarism, and self-plagiarism in our special project “Author’s work”.
Richard FEYNMAN Cargo cult science
American physicist Richard P. Feynman, a Nobel laureate, was always very scrupulous about the quality of a research study. During his commencement address at the California Institute of Technology in 1974, he talked about scientific integrity and honesty and warned young researchers “not to fool” themselves. A must-read for anyone who believes he/she is a true scientist.
Ivan PAVLOV On the Russian mind
In 1918, Russian physiologist Ivan Pavlov, a Nobel laureate, delivered two lectures: on the mind in general and the Russian mind in particular; on those mind qualities that determine the success of a research work and on how these qualities are present in the Russian mind. Pavlov's thoughts are an effective vaccine against poor intellectual work.