Personalization of selecting a target for rTMS is a problem, solving which can significantly increase the method efficacy. Stimulation of the key hubs of individual-level resting-state networks represents an approach to personalization. The study aimed to develop an rTMS personalization method based on the selection of individual frontoparietal control network (FPCN) hubs and assessment of their localization variability. To determine the FPCN hubs, individual maps were built using the FPCN group mask as a seed. The searchlight algorithm with the sphere radius of 5 mm was used to select targets within the dorsolateral prefrontal cortex (DLPFC) and posterior parietal cortex (PPC). The target spatial localization variability and correctness of using the routine “5 cm rule” for the DLPFC localization were analyzed. In 24 healthy volunteers (9 males, average age 29±7 years), high interindividual variability of targets was demonstrated. In no area is there a universal position of the stimulation coil that would effectively stimulate targets in all volunteers. Spatial dispersion of points is higher in the DLPFC (volumes of the polyhedral containing the point sets are 2095 mm3 in the DLPFC and 739 mm3 in the PPC). All individual targets in the DLPFC are located within the FPCN mask, while in the PPC some targets are outside this mask. The average distance between the М1 zones and DLPFC is 64±13 mm. In 75% of the subjects, this exceeds 5 cm, which confirms that it was incorrect to use the routine “5 cm rule” for coil positioning in the majority of subjects. An algorithm to select personalized targets for rTMS based on the resting-state fMRI data in the DLPFC and PPC being the key FPCN hubs has been developed.
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The use of allogenic bone material as a ceramic filler for DLP printing makes it possible to obtain personalized complex-shaped implants combining the matrix biomimetic nature with the additive technology benefits. The study aimed to assess the possibility of using the calcined cortical bone allograft powder as part of photopolymerizable suspension for DLP printing and producing bioceramics with the characteristics comparable to that of synthetic hydroxyapatite by sintering. The bone allograft was subjected to multi-stage specialized treatment involving complete removal of cells with preservation of the intercellular matrix and collagen fiber structure. The calcined medical allograft was crushed, introduced into a photopolymerizable matrix, and used for DLP printing of the samples that were further sintered and analyzed by X-ray diffraction and energy-dispersive spectroscopy methods before and after additive production. The sintered material specific gravity was 81.5%, compressive strength — 75.8 MPa, tensile strength — 12 MPa, Young's modulus — 3.08 GPa, and Vickers hardness — 0.55 GPa, which was within the range of values for porous hydroxyapatite. After DLP printing and sintering the sample phase and elemental composition did not change considerably compared to the source calcined material. The calcined bone allograft powder is suitable for preparing photopolymerizable suspensions and subsequent DLP printing of ceramic samples without deteriorating the material phase and chemical stability. The resulting mechanical properties make it possible to consider this allogenic bone material as a promising candidate for production of personalized implants with sophisticated geometry.
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Atherosclerosis being the main cause of myocardial infarction and stroke remains a global medical and social problem. Despite the fact that it is recognized as a chronic inflammatory disorder, the intracellular molecular mechanisms that drive the disease progression are poorly understood. The CDK8 and CDK19 cyclindependent kinases being the key regulators of transcription and inflammation can potentially play an important role in the atherosclerosis pathogenesis. The study aimed to assess the impact of the Cdk8 and Cdk19 gene knockout on the development of atherosclerotic lesions in apolipoprotein E-deficient mice (ApoE⁻/⁻). It has been shown that both endothelium-specific and systemic Cdk8 knockout significantly reduce the area of atherosclerotic aortic lesions, and the total knockout has a more prominent anti-atherogenic effect. This suggests a pleiotropic role of CDK8 in the atherosclerosis pathogenesis mediated by its function not only in endothelial cells, but probably also in macrophages. In contrast to Cdk8, the systemic Cdk19 knockout had no significant effect on the development of atherosclerosis. Thus, CDK8, but not CDK19, has been identified as a pro-atherogenic regulator, which makes it a promising target for the development of novel therapeutic strategies.
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Chronic endometritis (CE) is the most significant endometrial disease in terms of its impact on reproductive potential. Thus far, pathogenetically significant inflammatory markers — cytokines, inflammatory proteins, and hematological indices — have not been widely used in medical practice for the diagnosis of CE. This study aimed to evaluate indicators of systemic inflammation, including hematological parameters and inflammatory indices, in patients with infertility, and to determine their diagnostic significance for CE. We analyzed the data of examinations of 50 patients with infertility. The standard hematological method was used to determine the leukocyte count. Based on the blood cell composition, we calculated the inflammatory indices NLR, MLR, PLR, and SII. The concentration of CRP in the blood serum was determined by enzyme immunoassay. In patients with CE-associated infertility, the absolute and relative numbers of lymphocytes were lower (p = 0.0451 and p = 0.0089, respectively), whereas the relative numbers of monocytes and basophils were higher (p = 0.0469 and p = 0.0005, respectively) than in patients without CE. In the study group, the concentration of CRP in the blood was almost four times higher than in the control group (p = 0.0191), but all indicators remained within the normal range. A comparative analysis of the NLR, MLR, PLR, and SII indices revealed their significant growth in CE-associated infertility cases (p = 0.0387, p = 0.0058, p = 0.0335, and p = 0.0333, respectively). ROC analysis established the predictive significance of NLR (0.871 (95% CI: 0.767–0.974); p < 0.0001) and MLR (0.848 (95% CI: 0.737–0.958); p < 0.0001) indices for detecting CE in infertility patients.
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The risk of contamination by cervical microbiota during transcervical sampling represents a fundamental methodological challenge in endometrial microbiome research. This study aimed to experimentally evaluate the efficacy of Pipelle and Endobrush endometrial sampling catheters in preventing this contamination. An in vitro cervix model with two anatomically distinct canal types (cylindrical and slit-like) was developed and filled with a synthetic cervical mucus containing a defined quantity of bacterial DNA. After catheter passage through the model cervical canal, a simulated ‘endometrial’ sample (sterile air) was collected and subjected to quantitative PCR analysis. Both catheter types facilitated substantial transfer of bacterial DNA from the cervical mucus into the endometrial sample. The median transfer of total bacterial DNA was 81.6% [54.4–107] for the Pipelle catheter and 29.8% [14.8–56.3] for the Endobrush catheter (p = 0.009), indicating that neither device provided sufficient protection for reliable characterization of the endometrial microbiota. Catheter efficacy was further dependent on cervical canal morphology and the specific microbial group analyzed. These findings demonstrate that transcervical sampling with either catheter type introduces a significant and variable degree of cervical contamination, thereby confounding the interpretation of endometrial microbiota data and underscoring the need to conceptualize and study a combined cervico-endometrial microbiota.
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Pregnancy requires the cells of the woman’s body to ensure increased ribosomal biogenesis in order to enhance the protein synthesis intensity. The number of ribosomes depends on the copy number of ribosomal genes (rDNA) in the genome. The study aimed to test the hypothesis about the association of the rDNA copy number in the woman’s genome with the course of normal and complicated pregnancy. The sample of 488 pregnant women (25–39 weeks) included the following groups: 1) normal pregnancy (control); 2) impaired uteroplacental blood flow and fetoplacental insufficiency; 3) congenital malformations; 4) isthmic-cervical insufficiency; 5) early placental maturation; 6) dichorionic diamniotic twins; 7) polyhydramnios; 8) macrosomia. The rDNA copy number was determined by the quantitative hybridization method in the DNA extracted from peripheral leukocytes.  The rDNA copy number varied between 226 and 800 (n = 488). DNA samples with the rDNA copy number below 290 were lacking in groups 3–8. Groups 5–8 included no samples with the rDNA copy number exceeding 520; these in total differed from group 1 by low rDNA copy number values (the average values were 360–381 for groups 3–8 and 452 for group 1; p < 10–7). The rDNA copy number range of 290–520 in the woman’s genome (the adaptive norm typical for long-lived individuals) is optimal in terms of successful completion of pregnancy in the presence of pregnancy complications. The low rDNA copy number (200–290) in the genome is associated with the failure to complete embryogenesis when there are some fetal abnormalities/ features. A high rDNA content (over 600 copies) indicates the presence of genetic variants in the woman's genome that can interfere with the complicated pregnancy course. Determining the rDNA copy number in the genome of married couples may be useful for planning and predicting the course of pregnancy.
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Memory in all the variety of the types and processes ensuring its functioning has a psychotherapeutic resource that is realized when working with manifestations of post-traumatic stress disorder (PTSD). One of these is obsessive repetitive memories with traumatic content. The study aimed to look into reconsolidation of early memories in reliving the traumatic experience of participation in combat. The total sample size was 62 individuals (males aged 21–46 years). The experimental group included 31 respondents with combat experience having the status of war veterans (the average period of participation was 1 year and 5 months). The control group consisted of 31 respondents with no combat experience. The Mini-Mental State Examination (MMSE) scale, set of functional neuropsychological tests (“10 Words” by A.R. Luria, "Pictograms" method by A.R. Luria, "Difficult-to-Verbalize Figures" by T.V. Akhutina, "Rhythm Reproduction Test" by A.R. Luria), analysis of the transcripts of audio recordings of early memories were used. It has been reliably found that the early memory of a positive, negative or neutral modality resulting from the influence of combat experience is changed through the reconsolidation mechanism, which is reflected in the linguistic and semantic parameters. The linguistic and semantic structure of the combat veterans’ early memories is characterized by the event-based model, with a predominance of verbs and adverbs. The semantic core of the combat veterans’ early memories is more often negatively colored, despite the general ambivalent or positive modality.
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