Journal «MEDICINA» 3/2026

Significance.  Globally, there is a steady increase in healthcare expenditures accompanied by a simultaneous decline in the accessibility of medical care. A crisis of trust is escalating among patients, healthcare professionals, and administrative bodies. Insurance-based principles of healthcare organization and financing remain dominant in modern medicine. Efforts to identify strategies for reducing risks, lowering costs, improving accessibility, and restoring trust have proven ineffective. Research Objective. To analyze the conflict between the humanitarian mission of medicine and the economic incentives embedded in dominant «fee-for-volume» models (fee-for-service, case-based payment), and, based on this analysis, to formulate conceptual proposals for the discussion on reforming healthcare financing in Russia. Materials and Methods. Evolutionary-biological analysis, economic-behavioral analysis, sociological and historical-cultural modeling, systems analysis, comparative method. Results. The dialectical interaction of biological instincts (competition, accumulation drive) and social norms (altruism, cooperation, justice) is one of the significant factors in the development of society and models of healthcare organization. Dominant fee-for-service payment systems enter into an antagonistic contradiction with the specific humanistic nature of medicine. The fundamental conflict between market economic mechanisms and the humanistic nature of medicine distorts the professional values of physicians and undermines trust-based relationships with patients. Budgetary models, through a system of public regulation and estimated financing, create an environment conducive to the manifestation of humanism and, given adequate resource provision, demonstrate high efficiency. Conclusions.  A civilizational choice in favor of abandoning market dogmas in healthcare is necessary. A roadmap for key reform directions for Russia is proposed.

Key words: evolutionary biology, biosocial determinants, healthcare financing, fee for volume, value based payment, Semashko system, budget financing, Singapore, medical ethics, physician motivation, healthcare reform

Introduction. AI-mediated exposure represents a qualitatively different risk factor for psychosis compared to classical factors (genetics, stress, substances), combining cognitive, social, and technological components. Objective. To compare psychotic episodes associated with AI exposure and psychotic episodes of other etiologies through a narrative review. Methods. A search was conducted on Lens.org (1995–2026) with verification in PubMed and Google Scholar. Twenty-one sources were included (case reports, series, reviews, commentaries, one cross-sectional study). No studies designed for direct group comparisons were identified. Results. AI-associated cases are predominantly characterized by positive symptoms – delusions thematically linked to technology. Negative symptoms and formal thought disorders have not been reported. Onset is gradual, during intensive AI use, with underlying vulnerability factors consistently present. Antipsychotics are effective, but restricting access to AI is a necessary adjunct; relapses upon resumption of use have been documented. Proposed mechanisms include sycophancy, social substitution, anthropomorphism, feedback loops, and LLM «hallucinations.» Conclusion. The evidence base is insufficient for definitive conclusions. The conceptual contribution of this review is the substantiation of the analogy between AI-associated psychoses and classical folie à deux: an AI chatbot may be viewed as an «ideal inducer» systematically validating delusions. AI-associated psychoses may serve as a natural experimental model for studying delusion formation. Prospective cohort studies are needed.

Key words: artificial intelligence, AI, psychosis, generative neural networks, large language models, chatbots, delusions, induced delusional disorder, folie à deux, digital psychiatry, sycophancy

Introduction. The relevance of the study is determined by the need to improve methods for the quantitative determination of duloxetine, a modern antidepressant, in biological objects to optimize therapeutic monitoring and toxicological diagnostics. Monitoring drug concentrations in the patient's body is necessary due to individual metabolic characteristics, the risk of side effects, and the possibility of overdose. Objective. To develop and validate a bioanalytical method for the quantitative determination of duloxetine in biological fluids of laboratory animals using high-performance liquid chromatography (HPLC). Materials and Methods. The study used the pharmaceutical product «Duloxetine Canon» as the test object and Duloxetine Hydrochloride reference standard (Supelco) for calibration. Experiments were carried out on 30 Wistar rats that received the drug intragastrically at a dose of 300 mg/kg; serum and urine samples were collected for analysis. A sample preparation procedure using liquid-liquid extraction was developed; chromatographic conditions were optimized (mobile phase acetonitrile–phosphate buffer, detection at 231 nm). Validation was performed for selectivity, linearity, limit of quantification, accuracy, precision, stability, and matrix effect. Results. The method has a limit of quantification of 6 μg/mL, a linear range of 6–160 μg/mL, and a relative error of no more than ±1.57%. The developed approach effectively determines duloxetine in blood serum and urine at 30, 60, and 180 min after administration, which expands the possibilities of toxicological monitoring. For chemical-toxicological analysis of a toxic dose of duloxetine, it is advisable to examine both biological fluids. Conclusion. The created tool can be used for monitoring therapeutic concentrations and diagnosing poisoning, which contributes to the safe use of duloxetine in clinical practice. The method is suitable for both diagnostic purposes and scientific research in the pharmacokinetics of antidepressants.

Key words: duloxetine, bioanalytical method, high-performance liquid chromatography, laboratory animals, method validation

Introduction. Overexpression of epidermal growth factor receptor (EGFR) is characteristic of a number of malignant neoplasms, making it an important molecular target for targeted radionuclide imaging. The designed ankyrin repeat protein DARPin (HE)₃-E01 with subnanomolar affinity to EGFR is considered as a promising chemical precursor for the preparation of radiopharmaceuticals labeled with technetium-99m or iodine-123. To be introduced into pharmaceutical practice, a set of validated quality control methods for this protein is required. Objective. To develop and validate methods for identification, purity assessment, and quantification of the DARPin (HE)₃-E01 protein.

Materials and Methods. Identity was confirmed by liquid chromatography–electrospray ionization mass spectrometry (LC-ESI/MS) and sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). Quantification was performed using direct UV spectrophotometry at 280 nm and the bicinchoninic acid (BCA) colorimetric assay. Validation was conducted according to the criteria of specificity, linearity, accuracy (standard addition method), and precision (repeatability, intermediate precision). The two quantitative methods were compared using the F-test and t-test. Results. Mass spectrometric analysis showed complete agreement between the experimental molecular mass (18,260.29 Da) and the theoretically expected value (18,260.25 Da). Electrophoretic determination of molecular weight gave a value of 18.1 kDa, and the protein purity was at least 99%, with impurity content not exceeding 1%. Both quantitative methods demonstrated linearity over the studied concentration range (correlation coefficients of 0.9979 and 0.9997), high accuracy (CV not more than 2% for both methods), and precision (RSD <2%). No statistically significant differences were found between the results of the two methods (p > 0.05). Conclusion. The developed methods for identification and quantification of DARPin (HE)₃-E01 have been successfully validated and can be included in the draft regulatory documentation for quality control of the chemical precursor intended for the preparation of EGFR-targeted radiopharmaceuticals.

Key words: DARPin, EGFR, chemical precursor, quality control, method validation

Objective. To analyze the cognitive factors of remission in alcohol dependence with comorbid recurrent depression, with an emphasis on data from systematic reviews and meta-analyses. Methods. A narrative synthesis of data from randomized controlled trials, cohort and observational studies, systematic reviews, and meta-analyses published between 2000 and 2026. Searches were conducted in PubMed, Web of Science, Scopus. Results. The results of studies characterizing the degree and structure of cognitive deficits, as well as their psychological and neurophysiological mechanisms in the context of remission formation, are summarized. Conclusion. Promising directions for further research and the potential application of the obtained data in the development of individualized treatment are outlined.

Key words: alcohol dependence, comorbid depression, cognitive functioning, remission

Objective. To analyze the main characteristics of the tick-borne encephalitis (TBE) epidemic process in the Altai Krai during the modern period (2000–2024) and to evaluate the effectiveness of specific and nonspecific prevention on morbidity. Methods. The study is based on state statistical reporting data (Form No. 2), Rospotrebnadzor reports, and the results of entomological and virological surveillance (PCR, whole-genome sequencing). The study employs retrospective epidemiological analysis, calculation of intensive rates, Spearman's correlation analysis (r), Z-test for significance (p), as well as autocorrelation and Fourier spectral analysis to assess cyclicity. Results. The long-term average TBE incidence in the Altai Krai was 2.41±0.32 per 100,000 population, which exceeds the national average (2.06±0.04) by 16.99% (p<0.001). By 2024, incidence decreased 5.78-fold (to 0.90±0.21). A 10-year cyclicity of incidence and a 6-year cyclicity of the abundance and virus prevalence of ixodid ticks are revealed. The proportion of severe TBE forms was 43.78±1.31%; 25 fatal cases were recorded (all unvaccinated). An inverse correlation is demonstrated between incidence and the volume of vaccination (r=-0.32; p<0.05), emergency seroprophylaxis (r=-0.59; p<0.05), and the area of acaricide treatments (r=-0.70; p<0.05). No significant differences in incidence between urban and rural populations are found (p=0.763). Conclusion. The modern period (2000–2024) is characterized by the stabilization of TBE incidence in the Altai Krai at levels close to the national average due to increased volumes of vaccination, seroprophylaxis, and acaricide treatments. The identified 6-year cyclicity of tick virus prevalence allows forecasting of incidence dynamics. The absence of urban–rural differences indicates a significant role of anthropurgic foci, which requires their additional monitoring. Recommendations are given on the use of the obtained data for planning anti-epidemic measures in endemic regions.

Key words: tick-borne encephalitis, Altai Krai, epidemic process, vaccine prophylaxis, ixodid ticks, virus prevalence

Despite the success of vaccination, hepatitis B remains a common infectious disease for many years, with fatal outcomes such as liver cirrhosis and hepatocellular carcinoma. The leading role in the epidemiology of hepatitis B is played by the incidence among unvaccinated individuals or those who have not completed vaccination, due to their lack of immunity to the pathogen. The aim is а retrospective epidemiological analysis of the incidence of acute hepatitis B in the population of the Republic of Tatarstan. Methods. Data from reporting forms were analyzed using a descriptive epidemiological study methodology in R (version 4.3.2) and Microsoft Excel (2016). Incidence rates per 100,000 people in the Republic of Tatarstan and the patient structure by gender, age, and social factors were determined. Comparisons of indicators were conducted using the Student's t-test and the Pearson chi-square (χ2) test. Results. In the Republic of Tatarstan, the average long-term incidence rate for 2010-2024 was 0.45 ± 0.28 (95% CI: 0.30–0.60), with a minimum in 2020 (0.13 per 100,000 population) and a maximum in 2010 (1.23 per 100,000 population). The incidence rate decreased by 4.6 times. Men are statistically 1.9 times more likely to get sick than women, with men accounting for 61.4 % of cases. The age structure is dominated by people aged 25–44 (55.8%). The median age of those infected shifted from 29 to 40 years, indicating a shift in incidence toward older age groups. Both employed (43.8%) and unemployed (43.4%) individuals are affected almost equally. Conclusion. Despite the steady downward trend in the incidence of acute hepatitis B, the infection remains relevant for all age, sex and social groups of the population, with an emphasis on the group of people not included in the vaccination program as the most vulnerable. 

Key words: acute hepatitis B, incidence, age, gender, social group

Introduction. Ventilator-associated pneumonia (VAP) remains one of the most common and critical complications in patients receiving artificial lung ventilation (ALV) in intensive care units (ICUs). It is characterized by high morbidity, increased hospital stay and mortality. Assessing the epidemiological risk is an important task for developing effective prevention measures to improve the quality of medical care. The objective. To analyze the results of scientific research on methods and approaches to studying the epidemiological risks of developing ventilator-associated pneumonia (VAP) in intensive care units (ICUs), as well as existing prevention and control strategies. Materials and Methods. The study examined the results of scientific research on VAP published in major electronic databases using keywords related to VAP, ICU, mechanical ventilation, epidemiological risk, and prevention. The review includes original research, systematic reviews, meta-analyses, and clinical guidelines. Results. A wide range of risk factors for the development of VAP has been identified. To reduce the risk of VAP development, a comprehensive assessment of various epidemiological factors is necessary, based on an integrated analysis of patient data, hospital environment factors, and staff actions in the context of the organization of ICU work. Conclusion. A promising area of prevention is the development and application of digital technologies for comprehensive risk analysis, which takes into account both clinical and environmental factors, as well as staff actions.

Key words: ventilator-associated pneumonia, intensive care units, mechanical ventilation, hospital infections, epidemiological risk, prevention, risk factors

The article presents the experience of the Orenburg branch of The S. Fyodorov Eye Microsurgery Federal State Institution in the use of the technology of closing macular holes using ACT. The obtained results indicate a significant improvement in the anatomical and functional parameters of the retina. Successful regeneration of the macula and statistically significant increase in visual acuity in the operated patients indicate the prospects of this method in ophthalmosurgical practice.

Key words: macular hole, retina, subtotal vitrectomy, autologous cellular technology (ACT), patient's blood plasma

Introduction. Drug resistance of the human immunodeficiency virus (HIV) remains one of the key challenges in modern infectious diseases, significantly affecting the effectiveness of antiretroviral therapy and long-term disease prognosis. The high genetic variability of HIV contributes to the rapid emergence of resistance mutations and complicates the selection of effective treatment regimens. Objective. To analyze current data on the molecular mechanisms of HIV drug resistance, evaluate their clinical significance, and review modern approaches to the diagnosis and optimization of antiretroviral therapy. Materials and methods. A review of Russian and international scientific publications on HIV drug resistance mechanisms published in recent years was performed using specialized medical databases. The analysis included data from clinical and experimental studies, systematic reviews, and clinical guidelines focusing on resistance mutations, diagnostics, and treatment of HIV infection. Results and discussion. Drug resistance development is associated with the accumulation of mutations in genes encoding reverse transcriptase, protease, and integrase, as well as with the impact of viral genetic variability and subtype diversity. Cross-resistance and compensatory mutations play an important role in maintaining viral replicative capacity. Modern diagnostic methods, including genotypic and phenotypic testing as well as next-generation sequencing technologies, allow detection of minor viral variants and improve the prediction of treatment efficacy. Clinical evidence indicates that both transmitted and acquired resistance significantly influence the risk of virological failure and the choice of treatment regimens. Conclusion. Genetic variability of HIV and the emergence of resistance mutations are key factors determining the effectiveness of antiretroviral therapy. The use of advanced diagnostic methods and personalized treatment approaches can improve therapeutic outcomes and reduce the spread of drug-resistant HIV strains.

Key words: HIV, drug resistance, antiretroviral therapy, mutations, genotyping, virological failure

Hemolytic-uremic syndrome (HUS) is a thrombotic microangiopathy characterized by thrombocytopenia, microangiopathic hemolytic anemia, and acute kidney damage. Typical HUS is most often caused by Shiga toxin, produced by some Escherichia and Shigella. The ability of Shiga toxin to bind to globotriaosylceramide on the surface of target cells (endothelial cells, podocytes, and renal tubular epithelium) leads to acute kidney damage and neurological symptoms. The pathogenesis, clinical manifestations, and treatment of typical GUS are widely discussed in pediatric practice. However, there are only a few reports of typical GUS in older individuals. In this report, we present a clinical case of a 67-year-old patient with a typical HUS who developed an acute intestinal infection of mixed etiology (E. coli + Shigella). We describe the clinical manifestations of the patient's acute intestinal infection. The development of a typical HUS in this patient was accompanied by complications such as bilateral pneumonia, sepsis, and multiple organ failure. The dynamics of hematological parameters showed a significant decrease in the number of red blood cells and platelets, while the levels of creatinine and urea increased. The article describes the treatment methods used to achieve a favorable outcome of the disease. This clinical case illustrates the classic combination of thrombocytopenia, anemia, and uremia in a typical case of GUS, which is accompanied by a severe mixed infection of shigellosis and escherichiosis. Stage 3 hypertension in the observed patient predisposes to the development of complications such as thrombotic microangiopathy. It is hypothesized that the Shiga toxin produced by Enteroinvasive Escherichia coli, which was detected in the patient, triggered the development of HUS in this clinical case. The study concludes that it is necessary to identify elderly individuals with acute intestinal infections caused by Escherichia coli and Shigella.

Key words: Hemolytic uremic syndrome, Shiga toxin, escherichia coli infection, shigellosis, case report