Annals of the Russian academy of medical sciences

Background. Neuronal damage is an important component of the pathogenesis of hemorrhagic stroke, but cellular and molecular markers of neuronal changes during the acute phase of the disease in humans have been poorly studied. One neuronal marker is the nuclear protein NeuN. Opinions on the use of NeuN as a marker of neuronal damage are contradictory. The heterogeneity of immunohistochemical (IHC) staining described in studies under various pathological and physiological conditions creates the basis for studying NeuN as a marker of the functional state of neurons in various diseases. This study aims to identify the distribution patterns of NeuN in the layers of the human cerebral cortex during the acute phase of hemorrhagic stroke. Aims — to identify the features of NeuN distribution in the layers of the human cerebral cortex in the acute phase of hemorrhagic stroke. Methods. A retrospective analysis of forensic medical examination materials was conducted from February to September 2019 and from January to February 2022. The study included cases in which the causes of death were: 1) non-traumatic subarachnoid hemorrhage (SAH group); 2) sudden cardiac death (SCD) or coronary artery disease (CAD) (control group). Standard histological processing was then performed with embedding in paraffin blocks, from which sections were prepared and stained with hematoxylin and eosin. Morphological examination of neurons was performed using immunohistochemistry with antibodies to the NeuN protein. Morphometry was performed on micrographs obtained using a scanner. Results. 16 cases were selected for the IHC study, 10 of which were SAH and 6 were SCD/CHD. In the SAH group there were 5 men and 5 women, median age — 62.5 (57.0–76.5), in all observations SAH was of basal localization. The control group included 3 men and 3 women, median age — 58.5 (46.0–73.2), in all observations the cause of death was sudden coronary death. As a result of comparison of SAH and control groups, the following significant results were obtained: in the first layer, there were more fully stained neurons in the SAH group than in the control group (22.9 ([13.6–46.4) vs. 0 [(0–6.9); p = 0.001); in the third layer, there were more unstained neurons in the SAH group than in the control group (22.7 ([16.8–37.8) vs. 5.4 [(0–9.5); p = 0.005). In the fifth layer, there were more neurons with stained nuclei but unstained cytoplasm in the control group than in the SAH group (42.3 ([28.1–73.6) vs. 22.4 [(8.6–35.8); p = 0.031). Conclusion. This study is the first to demonstrate an association between subarachnoid hemorrhage and changes in NeuN staining of neurons in human cerebral cortex. These results confirm that the use of NeuN immunohistochemical staining should not be limited to the detection of intact neurons.

Addressing the problem of illicit drug trafficking for non-medical use remains a global challenge for the global community, and remains relevant in the 21st century. Determining global, national, and regional trends in narcotic and psychotropic substance consumption, assessing the epidemiological situation (incidence, prevalence), harm structure, and law enforcement indicators (seizures, trafficking routes) are necessary for developing a systemic response to drug-related violence at all levels. This article explores the rationale for transitioning the Kabardino-Balkarian Republic’s anti-drug policy from a reactive model to proactive management based on the principles of a cybernetic viable system and anticipatory governance. Based on an analysis of global and regional trends, it has been established that the drug situation has entered a synthetic-polytoxicological phase, with a predominance of preclinical risk, an increase in acute poisonings, and a lack of synchronicity between law enforcement and medical indicators. The study’s materials included regional administrative reports (Forms No. 11 and No. 37) for the period from 2014 to 2024, records of the Anti-Drug Commission and the Ministry of Internal Affairs of the Kabardino-Balkarian Republic, and structured tables on mortality and poisoning. Descriptive statistical methods were used, including comparative-analytical, structural-functional, and modeling research methods. The study demonstrated the effect of asymmetric adaptation — the ability of the illegal market to change chemical formulas and distribution channels faster than control measures can be updated. The aim of the study was to justify the need to implement a three-loop anticipatory management system: monitoring predictive patterns, scenario-based predictive assessment of probabilistic trajectories, and adaptive adjustment of measures in real time. According to the researchers, the proposed digital toxicology surveillance architecture will reduce the time lag between risk and response, shift from recording consequences to managing probabilities, and increase the resilience of the regional healthcare system to new forms of drug addiction.

Currently, immuno-oncology is a rapidly developing field of medicine, primarily due to the integration of achievements in molecular biology and biotechnology (creation and production of modified cells and effector molecules), immunological physiology (understanding of subtle mechanisms of regulation of immune functions) and clinical medicine (adequate accompanying therapy, allowing manipulation of the patient’s immune system). A large number of tumors overexpress tumor-associated gangliosides (sialylated glycosphingolipids). For example, GD3, GD2 and GM2 are overexpressed in melanoma and neuroblastoma cells, increased expression of GD1a, GM1, GM2 is shown in carcinoma cells, GD2 is expressed by soft tissue sarcoma, osteogenic sarcoma and small cell lung cancer cells. The ratio of the number of gangliosides varies from one tumor type to another. In addition, gangliosides are found in neoplastic tissues that are not characteristic of normal transformed cells of this tissue. In particular, one such ganglioside is GD2. In normal cells, the expression of this ganglioside, as well as that of GM2, is restricted to nerve cells, but in the case of cancer transformation they are found in cells of malignant tumors. Numerous studies have shown that tumor-associated gangliosides arising from oncogenic transformation play a key role in invasion and metastasis of a number of tumors and induce tumor-associated angiogenesis. First of all, it has been established that tumor cells differ in the composition of gangliosides. the ganglioside composition of metastasis cells differs from the cells of the primary tumor focus and is characterized by a decrease in the content of complex gangliosides. Due to its high level of expression in a number of tumors and limited expression in normal tissues, ganglioside GD2 can be considered as an ideal potential target for the development of anti-tumor immunotherapies.

Background. An algorithm for the personalized selection of SSRIs based on pharmacogenetic testing is currently available. Personalization algorithms for adults are not applicable to teenagers. Previously, contradictory results were obtained regarding the association of “ultrarapid” CYP2C19 metabolism and poorer tolerability of sertraline and escitalopram. Our aim was to assess the relationships between CYP2C19*2, *3, and *17 polymorphisms and early adverse drug reactions to sertraline among adolescents with depressive episodes and suicidal intentions. Methods. Study design: observational prospective single-center. The study included 133 adolescents (89% female) with a depressive episode and suicidal tendencies. All patients received sertraline. On day 7, the safety of pharmacotherapy was assessed using the Antidepressant adverse drug reactions checklist. Each patient underwent genetic testing for CYP2C19*2, *3, *17. Statistical processing of the results was carried out using IBM SPSS Statistics 26.0. The safety of sertraline was analyzed depending on the carriage of CYP2C19 polymorphisms, the type of CYP2C19 metabolism, as well as depending on additional pharmacotherapy. Results. 96 patients had “normal” CYP2C19 metabolism, 27 had “intermediate” metabolism, 8 — “ultrarapid” metabolism, and 2 — a “poor” metabolism. There were no significant associations of the number of ADRs, as well as the frequency of individual ADRs, depending on the type of CYP2C19 metabolism. Carriage of CYP2C19*17 (CT+TT genotypes) was significantly associated with a large number of somatic and vegetative adverse drug reactions on day 7 (2 (1; 3) vs. 1 (1; 2); p = 0.017). On day 7, carriers of CYP2C19*2 (genotype GA+AA) were more likely to complain of sleep disorders (13 (46.4%) vs. 28 (26.7%); p = 0.044) and tremor (7(25%) vs. 9 (8.7%); p = 0.018) compared with homozygotes GG. Conclusion. Carriage of the CYP2C19*17 was significantly associated with an increase in somatic and vegetative ADRs frequency. This result is paradoxical, as carriage of CYP2C19*17 is more likely to lead to accelerated metabolism of sertraline. Carriage of the CYP2C19*2 was only associated with a higher frequency of sleep disturbances and tremor.

Background. Among the factors contributing to unsuccessful treatment outcomes in patients with drug-resistant pulmonary tuberculosis-particularly multidrug-resistant tuberculosis (MDR-TB)-considerable importance is attributed to interindividual variability in pharmacological response, which is largely determined by patients’ genetic characteristics. Recent advances in MDR-TB chemotherapy are closely associated with the introduction of bedaquiline. Bedaquiline is primarily metabolized by the cytochrome P450 enzyme CYP3A4; however, the impact of CYP3A4 gene polymorphisms on bedaquiline pharmacokinetics and treatment efficacy in patients with drug-resistant TB remains insufficiently studied. Personalized therapy based on a patient’s genetic profile represents a key strategy for optimizing dosing regimens, improving treatment efficacy, and reducing the risk of developing further drug resistance. Aims — to evaluate the influence of CYP3A4 polymorphic alleles (*1B/rs2740574 and *1G/rs2242480) on bedaquiline pharmacokinetic parameters and chemotherapy efficacy in patients with drug-resistant pulmonary tuberculosis, including those with MDR-TB. Methods. A prospective, observational cohort study was conducted involving 143 patients with pulmonary tuberculosis and confirmed drug-resistant Mycobacterium tuberculosis (including MDR, pre-XDR, and XDR-TB) treated at the Central TB Research Institute (CTRIT), Russia, between 2022 and 2024 (66 women and 77 men). Three observation groups were formed based on genotype: Group 1 — wild-type CYP3A4*1 (n = 99); Group 2 — *1B (rs2740574) carriers (n = 10); Group 3 — *1G (rs2242480) carriers (n = 34). Genotyping was performed using polymerase chain reaction–restriction fragment length polymorphism (PCR-RFLP). Bedaquiline was administered as part of individualized chemotherapy regimens at a dose of 400 mg once daily for 2 weeks, followed by 200 mg three times weekly for up to 6 months. Bedaquiline pharmacokinetic parameters were assessed in 30 patients using high-performance liquid chromatography. Treatment efficacy was evaluated based on sputum culture conversion by month 6. Statistical analysis employed nonparametric Kruskal–Wallis and Mann–Whitney tests for group comparisons. Results. Patients carrying the CYP3A4 *1G (rs2242480) allele showed significantly higher bedaquiline exposure compared to wild-type individuals: AUC₀_–₂₄ (49.06 vs. 41.99 µg·h/mL; p < 0.05), C_max (3.13 vs. 2.21 µg/mL; p < 0.05), and AUC₀_–₂₄/MIC ratio (196.24 vs. 167.94; p < 0.05), suggesting reduced metabolic clearance. In contrast, the *1B variant was associated with lower AUC₀_–₂₄. Although culture conversion rates at 6 months did not differ significantly (p = 0.87), a trend toward higher efficacy was observed in *1G carriers (95.8%) versus wild-type patients (84.5%). Conclusion. The CYP3A4 *1G (rs2242480) polymorphism is associated with decreased bedaquiline metabolism, leading to increased systemic drug exposure and a potential improvement in treatment response. These findings highlight the role of CYP3A4 genetics in bedaquiline pharmacokinetics and support the integration of CYP3A4 genotyping into personalized MDR-TB treatment strategies. The *1G allele may serve as a promising pharmacogenetic biomarker for optimizing bedaquiline dosing in drug-resistant tuberculosis.

On February 9, 2026, Mikhail Alexandrovich Piradov, an outstanding Russian scientist with a global reputation, a leading expert in neurology, neuroresuscitation, and neurorehabilitation, and a two-time recipient of the Government of the Russian Federation Prize in Science and Technology, celebrated his 70th birthday.

On January 1, 2026, Vladimir Petrovich Fisenko, a renowned Russian scientist, clinical pharmacologist, recipient of the Lenin Komsomol Prize, Honored Scientist of the Russian Federation, Doctor of Medical Sciences, Professor, and Academician of the Russian Academy of Sciences, celebrated his 80th birthday.

On February 11, 2026, Amiran Shotaevich Revishvili, an outstanding scientist and a leading expert in surgical and interventional arrhythmology, a recipient of the USSR State Prize and the Russian Federation State Prize, a two-time recipient of the Russian Federation Government Prize in Science and Technology, an Honored Scientist of the Russian Federation, a Doctor of Medical Sciences, Professor, and an Academician of the Russian Academy of Sciences, celebrated his 70th birthday.