Theta-burst stimulation (TBS) is widely used due to induction of the long-lasting effects with short protocol duration. To reduce the variability of the effect, approaches to personalize it, such as using theta-gamma coupling frequencies (TGC), are being investigated. The study was aimed to develop the personalized protocol of navigated intermittent theta-burst stimulation (iTBS-ind) based on TGC, and to compare this protocol with the standard one (iTBS-5/50) and sham stimulation (iTBS-sham). The study involved 16 healthy volunteers (М — 7; 29.6 years), who were randomized to receive one session of each protocol of the left dorsolateral prefrontal cortex iTBS. The effects were estimated using the n-back test with simultaneous presentation of verbal and spatial stimuli (n = 2, 3), Digit Span test, Corsi blocks task, Tower of London test; testing was performed immediately before, immediately after and 60 min after stimulation. No severe adverse events were reported. Significant effect was obtained when performing assessment after 60 min for iTBS-5/50 in the n-back test with spatial stimuli (n = 3) (pcorr = 0.018), for all protocols in the Tower of London test (pcorr = 0.039 for iTBS-5/50, pcorr = 0.045 for iTBS-ind, pcorr = 0.003 for iTBS-sham). The iTBS-5/50 effect was significantly higher compared to iTBS-sham in the spatial n-back test (n = 3) (pcorr = 0.039), but lower compared to iTBS-ind and iTBS-sham in the Corsi blocks task (pcorr = 0.038 and 0.048, respectively). Thus, we failed to confirm the personalized protocol efficacy and superiority to the standard protocol and sham stimulation. Considering the effect of standard protocol, its further investigation can be promising.
The regenerative medicine methods are being actively developed both in Russia and abroad due to relevance of this direction, especially in the field of the jaw osteoplasty. Autologous, allogeneic and xenoplastic materials, as well as the calcium phosphate ceramics synthetic preparations are conventionally used to normalize and stimulate osteogenesis, however, the treatment outcomes are not always unequivocal. The study was aimed to substantiate the use of the biocomplex consisting of plasma rich in growth factors (PRGF) and xenoplastic material to improve the jawbone osteogenesis efficacy. The study involved 136 patients (105 females and 31 males aged 21–67) divided into four groups based on the method of bone defect restoration. In group 1, no osteoplastic material was used; in group 2, osteoplasty involved the use of the PRGF fibrin gel; in group 3, the Osteobiol Gen-Os material was used; in group 4, osteoplasty involved using the combination of the Osteobiol Gen-Os material and plasma rich in growth factors (PRGF). Computed tomography and digital densitometry were performed before surgery and 3, 6, 12 months after it to assess the dynamics of osteogenesis. A year later restoration of the lost bone tissue volume was reported in 100% of patients in group 4, 70.27% of patients in group 3, 43.47% of patients in group 2, 37.5% of patients in group 1; Fisher's exact test revealed significant differences in the osteoplasty outcomes in groups 3 and 4 (p = 0.00002). There were significant differences in bone density between patients of groups 1 and 2 twelve months after surgery (p = 0.044), between patient of groups 3 and 4 three (p = 0.004), six (p = 0.0001) and 12 (p = 0.0001) months after surgery. The findings show that the method proposed is effective.
Circulating monocytes are important actors of the tumor growth pathogenesis. It has been shown that some features of the monocyte populations expressing endocytosis receptors or the major histocompatibility complex components are observed in blood of patients with breast cancer. The study was aimed to assess the relationship of tumor parameters and blood cytokine profile with the composition of circulating monocyte populations in patients with localized and locally advanced breast cancer. The study has shown that the circulating monocytes’ phenotypic characteristics are correlated to the clinical and morphological features of the neoplastic process. The content of populations with the CD14+CD16++CD163+ and CD14++CD16+CD163+ phenotypes positively correlates with the disease stage, while larger primary tumor size is associated with lower CD14+CD16++ monocyte levels. Elevated serum levels of IL8 and МСР-1 are observed in breast cancer patients. High IL6 levels in patients with breast cancer are associated with the reduced percentage of CD14++CD16-HLA-DR+, CD14+CD16++HLA-DR+ and CD14++CD16-СD163+ monocytes. Thus, CD163+ and HLA-DR+ monocytes are associated with the clinical and morphological parameters and blood levels of cytokines, which suggests that these populations are involved in breast cancer progression and indicates that further research is advisable for translation of the findings into clinical practice.
Genetic testing of each patient aimed at detecting the pharmacogenetic marker carrier state is challenging for healthcare system. However, knowledge about the frequencies of pharmacogenetically important genes enables making decisions about treatment based on the patient’s ethnicity. The CYP2C19 cytochrome gene involved in biotransformation of a broad spectrum of drugs is one of the most important. The study was aimed to determine the frequencies of major CYP2C19 variants and the patterns of their spatial variability in the population of Russia. The database Pharmacogenetics of the Population of Russia and Neighboring Countries created by the research team was used to determine frequencies of the CYP2C19 *1, *2, *3, *17 variants and their genotypes: *1 – 53 populations, n = 2261 samples; *2 — 79 populations, n = 6346; *3 — 92 populations, n = 7517; *17 — 35 populations, n = 3313. We have created a cartographic atlas that includes the *1, *2, *3, *17 frequency maps, correlation maps, and genotype frequency maps. Specific data on the frequencies of CYP2C19 variants and their pharmacogenetically significant genotypes in the major ethnic groups of Russia are provided. The cartographic atlas enables prediction of frequencies of significant CYP2C19 variants and their genotypes in the peoples, information about which is currently missing. The *1 and *2 variants gene geography is characterized by similar pattern: the combination of longitudinal trend of frequency increase from west to southeast and latitudinal variability of frequency increase from north to south in the Asian part of the region. Variant *3 is characterized by the clear longitudinal vector of frequency increase from 0 in the west to the world’s maximum in the Amur region. Variant *17 shows a pronounced longitudinal trend with the oppositely directed vector of frequency decrease from west to southeast. The correlation maps indicate regions, where the similarity between core patterns is disrupted.
With type 2 diabetes mellitus (DM2) as a concomitant disease, chronic cerebral ischemia (CCI) has a more severe course because of chronic hyperglycemia. Using resting state functional MRI (fMRI) data, this study aimed to investigate connectivity of cerebral neural networks in patients that have CCI with DM2 and without DM2. The study involved 257 CCI patients (81 male and 176 female, aged 50-85 years) some of whom had DM2. We assessed metabolic parameters, state of cerebral circulation, and cognitive functions. Resting fMRI was used for the analysis of structure of connectivity of cerebral neural networks. With false discovery rate (FDR) factored in, CCI patients with DM2 had values of some indicators of connectivity of cerebral neural networks at a level significantly lower than CCI patients without DM2 (p (FDR) < 0.05). Namely, the indicators in question were those of connectivity of right hemisphere's speech neural network, left hemisphere's parahippocampal region, and angular gyrus of the right hemisphere, which is an integral part of the brain's passive mode network. Also, CCI patients with DM2 had significantly poorer connectivity of anterior cingulate gyrus, part of the salient neural network, and superior temporal gyrus. There are significant changes in the cerebellar networks, too. Overall, the size and intensity of most of the neural networks studied in resting state are lower in CCI patients with DM2.
Tamoxifen therapy results in endometrial thickening in some patients with hormone-sensitive breast cancer (HSBC). The data on the impact of polymorphic variants of the CYP2D6 gene encoding the CYP2D6 enzyme of the cytochrome P450 family on the efficacy and safety of treatment with tamoxifen are controversial. A prospective cohort study was aimed to explore the association of CYP2D6*3, *4, *6 polymorphisms with the risk of endometrial thickness during adjuvant tamoxifen therapy for HSBC. A total of 145 patients with resectable HSBC, who received 20 mg of oral tamoxifen per day, were enrolled. The CYP2D6*3, *4, *6 polymorphisms were identified by real-time PCR. Endometrial thickness was measured by ultrasonography after 3, 6 and 9 months of endocrine therapy. The study showed that endometrial hyportrophy was more often found in patients having no alternative alleles after 3 months of follow-up (40% against 23.2% in the group of “poor” metabolizers; p = 0.034). Meta-analysis of all follow-up periods has revealed that “normal” metabolizers show a significantly higher rate of endometrial thickness than “poor” metabolizers (OR = 1.88; 95% CI = 1.27–2.79; p = 0.002). A lack of significant differences in indicators of the state of endometrium between groups of patients with different CYD2D6 genotypes and menopausal status requires further investigation.
Uncontrolled screen time is a worldwide menace to health of the population. Today, the state of neuropsychiatric health of schoolchildren depends on various factors, including screen time, i.e., the time they spend using mobile electronic devices. This study aimed to investigate how different screen time durations affect the said neuropsychiatric health of this population group. In the 2022–2023 academic year, we surveyed 109 Moscow schoolchildren (35 boys and 74 girls) using questionnaires compiled by A.M. Vane (identification of signs of vegetative symptoms) and S.K. Kulakov (identification of internet addiction). The mean age of the participants was 14.9 ± 0.12 years. The children were divided into two groups: those staying within the regulated limit of mobile screen time (group 1, n = 11), and those exceeding that limit (group 2, n = 98). In group 1, the average mobile screen time, as measured for one month, was 110.50 ± 10.00 minutes per day, in group 2 — 345.00 ± 15.00. The average Vane questionnaire scores differed significantly between the groups (p ≤ 0.01): 12.30 ± 1.89 points in group 1 and 22.54 ± 1.16 points in group 2. Signs of vegetative symptoms were registered in 45.9% of group 1 participants and 63.6% of group 2 participants (p ≤ 0.01). The average Kulakov questionnaire scores differed significantly between the groups (p ≤ 0.05): 28.7 ± 1.88 points in group 1 and 37.1 ± 1.09 points in group 2. Schoolchildren who exceed the regulated mobile screen time limit are at risk of developing vegetative disorders and internet addiction.
There are no actual statistical data on maxillofacial trauma, nor is there a published analysis addressing morbidity patterns, including cases requiring admission to maxillofacial surgery departments. Such data and the respective analysis could help to assess effectiveness of the maxillofacial trauma and diseases prevention and treatment measures, improve the emergency care approaches, identify problems in the medical aid system's maxillofacial surgery domain. This study aimed to analyze the aspects of emergency admission to hospitals for reasons requiring maxillofacial surgery. We processed hospital records of 15,227 patients admitted from 2018 through 2022. The analysis revealed the number of emergency maxillofacial cases to be at a fairly high level and show no downward trend. The majority of the patients are young, able-bodied men. Of all the admitted persons, 28.6% came to the hospital on their own; 22.9% were nonresidents and foreigners. The average hospital stay was 3.85 days, it did not change significantly during the studied period. The prevailing types of trauma were maxillofacial injuries and mandibular fractures. For 29.9% of patients with the latter type, the treatment method of choice was osteosynthesis. Up to 70% of all the patients needed to be followed-up by a maxillofacial surgeon after discharge. The mortality rate in maxillofacial surgery departments is extremely low; all such cases involved concomitant pathologies.