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In the spring 2022, the number of cases of severe acute hepatitis of unknown etiology was unusual increased in Europe. As an immediate response, the World health organization recommended active efforts to identify such cases at the international level. For monitoring of acute hepatitis in Moscow, patients with suspected liver disease were sent to Infectious Diseases Clinical Hospital No. 1. The goal: study of the structure of diseases occurring with liver damage in children hospitalized in 2022. Materials and methods: analysis of medical records of children hospitalized with a diagnosis of hepatitis from May 1 to December 31, 2022. Еpidemiological data (age, gender, parenteral manipulations, contacts with patients, travel abroad), clinical (fever, jaundice, etc.), laboratory parameters were assessed. Results: A total of 164 completed cases of hepatitis in children aged 5 months to 17 years were analyzed. 36 children met the criteria for probable severe acute hepatitis of unknown etiology. Age median was 7 years [2.25;11]. Girls made up more than half (21 (58.3%). Non-infectious genesis was established in 15 (41.6%). The infectious disease was verified in 11 (30.5%), of which adenoviral infection was detected in 2 children. In 9 (25%) children the etiology of hepatitis was not established. Conclusion. Various infectious and non-infectious diseases among hospitalized children lead to a significant increase in liver transaminases. Most acute hepatitis with unspecified etiology proceeded as an acute infectious disease and ended in recovery. The role of adenoviruses in the development of severe hepatitis in children was not confirmed in our study.

We represent a rare clinical case of infectious mononucleosis with hepatitis, caused by Epstein-Barr virus, complicated by rare secondary autoimmune hemolytic anemia associated with warm agglutinins in a 16-year-old patient. The disease was long-lasting, with a two-wave course of febrile fever. Signs of hepatitis with the development of anemia of moderate severity appeared during the second wave of febrile fever. The etiology of the disease was confirmed by the detection of Epstein-Barr virus DNA in blood and the detection of anti-VCA IgM antibodies to Epstein-Barr virus in the absence of anti-EBNA IgG antibodies. Hemolytic anemia was verified using markers of hemolysis (increased lactate dehydrogenase activity, decreased haptoglobin concentration), and positive results of a direct Coombs test. After successful initiation of prednisone therapy and clinical improvement, the patient was discharged from the hospital on the 24th day of disease to continue treatment on an outpatient basis (prednisone was replaced by methylprednisolone).This case demonstrates the development of a rare autoimmune complication in infectious mononucleosis caused by the Epstein-Barr virus.

Purpose. Determine the nature of tumor regression and possible complications associated with the retinotoxic effect of melphalan and carboplatin with local chemotherapy.Methods. A histological analysis of 19 enucleated eyes from 19 patients with retinoblastoma was performed after combined organ-preserving treatment, including systemic chemotherapy and local chemotherapy in various doses. The enucleated eyes were fixed in 10 % formalin and processed routinely for histological examination.Results. Significant changes in the tumor tissue such as tumor regression associated with the destruction of the tumor tissue and its replacement with fibrous tissue, glia proliferation, and the formation of petrificates were revealed. Complete regression of the tumor was detected in 3 out of 19 eyes, partial in 13 eyes. There were no signs of regression in 3 eyes. Tumor invasion into the choroid was found in 5 cases, into the anterior sector — in 3 cases, into the optic nerve — in 3 cases. The retrobulbar tumor was presented in 1 case. Retinotoxic complications revealed. Hemorrhagic changes associated with focal necrosis of the central retinal vessels (n = 4), destructive changes in retinal pigment epithelium (RPE; n = 10) associated with the accumulation of melphalan in RPE leading to atrophic processes in the retina. Complications in the form of secondary glaucoma, severe fibrosis and retinal detachment, despite the complete resorption of the tumor, led not only to loss of vision, but also hindered visualization of the fundus and substantiated the need for enucleation in 3 cases. In other cases, enucleation was performed due to continued tumor growth (n = 16) or progression during treatment (n = 3).Conclusions. Retinoblastoma can be controlled with local chemotherapy. However, clinical and morphological examinations of enucleated eyes revealed and confirmed, along with tumor resorption, intraocular complications as a result of the toxic effect of the drugs and the presence of active tumor tissue to varying degrees of therapeutic pathomorphism, which can be explained by the resistance of RB to these drugs. Thus, a further search is needed for drugs that destroy the tumor and minimize the retinotoxic effect.

The article deals with the global problem of plastic pollution of the environment. As a way to solve this problem, it is proposed to reduce the production of disposable plastic tableware with a subsequent transition to the use of products that will be safe for the environment and human health. This transition involves the development of innovative projects to create biodegradable tableware, and materials, equipment and technologies for its manufacture. The implementation of such projects involves not only the creation of product and technological innovations, but also the implementation of changes in the business processes of enterprises. For the effective implementation of these processes, it is proposed to use the developed system of change management strategies, which is distinguished by a detailed elaboration of a set of organizational measures, including measures to motivate personnel in order to reduce resistance to the changes. The choice of a specific change management strategy is determined by such criteria as the degree of their radicality, the period of execution and the allocated resources.

Pollen grains emitted from vegetation can release subpollen particles (SPPs) that contribute to the fine fraction of atmospheric aerosols and may act as cloud condensation nuclei (CCN), ice nuclei (IN), or aeroallergens. Here, we investigate and characterize the hygroscopic growth and CCN activation of birch, pine, and rapeseed SPPs. A high-humidity tandem differential mobility analyzer (HHTDMA) was used to measure particle restructuring and water uptake over a wide range of relative humidity (RH) from 2 % to 99.5 %, and a continuous flow CCN counter was used for size-resolved measurements of CCN activation at supersaturations (S) in the range of 0.2 % to 1.2 %. For both subsaturated and supersaturated conditions, effective hygroscopicity parameters, κ, were obtained by Köhler model calculations. Gravimetric and chemical analyses, electron microscopy, and dynamic light scattering measurements were performed to characterize further properties of SPPs from aqueous pollen extracts such as chemical composition (starch, proteins, DNA, and inorganic ions) and the hydrodynamic size distribution of water-insoluble material. All investigated SPP samples exhibited a sharp increase of water uptake and κ above ∼95 % RH, suggesting a liquid–liquid phase separation (LLPS). The HHTDMA measurements at RH >95 % enable closure between the CCN activation at water vapor supersaturation and hygroscopic growth at subsaturated conditions, which is often not achieved when hygroscopicity tandem differential mobility analyzer (HTDMA) measurements are performed at lower RH where the water uptake and effective hygroscopicity may be limited by the effects of LLPS. Such effects may be important not only for closure between hygroscopic growth and CCN activation but also for the chemical reactivity, allergenic potential, and related health effects of SPPs.

Purpose. To reveal predictors of small choroidal melanoma transpupillary thermotherapy efficiency using optical coherence tomography-angiography.Patients and methods. 34 patients with small choroidal melanoma at an average age of 55.0 ± 2.9 years were examined. Optical coherence tomography-angiography was performed on an OCT-Angiography Software for RS-3000 Advance Optical Coherent Tomograph, Nidek, Japan, before and 4 months after 1 session of transpupillary thermotherapy. Transpupillary thermotherapy (TTT) was performed with a Nidec DC 3300 diode laser.Results. Prior to TTT — a loop-shaped, cranked-convoluted with an uneven lumen heterogeneous nature of the vasculature of the tumor with numerous bends and interlacing, located under the vessels of the retina in the central zone; the area of neovascular vasculature is 32.82 mm2, the density is 12.42 %. The limiting avascular zone is on the periphery. Around melanoma is a homogeneous hyperreflective rim of dilated choriocapillaries. 4 months after 1 session of TTT in 24 (70.6 %) of 34 cases — occlusion of the choriocapillaries in the central and peripheral zone of the tumor (avascular regions), expansion of the large and medium vessels of the choroid around the focus — predictors of complete tumor devitalization (chorioretinal scar). In 6 (17.6 %) of 34 patients, occlusion of the choriocapillaries in the central zone, expansion of large and medium vessels of the choroid around the tumor, along its periphery and in the paracentral region, retinochoroidal anastamoses along the periphery and in the paracentral zone, heterogeneous neovascularization of the choriocapillaries around; decrease in the area of vasculature — 12.44 mm2, density — 6.15 %, (p < 0.05) — predictors of partial devitalization of small choroidal melanoma (residual tumor). In 4 (11.8 %) of 34 cases, tumor vessels in the tumor area, large and medium vessels of the choroid around, along its periphery and in the central zone, occlusion of the choriocapillaries in the central zone, retinochoroidal anastamoses in the periphery and in the central zone, heterogeneous neovascularization choriocapillaries around; vascular network area — 29.13 mm2, density — 10.17 %, (p > 0.05), lack of devitalization (continued growth).Conclusion. The introduction of optical coherence tomography-angiography revealed the predictors of the effectiveness of transpupillary thermotherapy of the initial melanoma of the choroid, which are various types of tumor vascularization, indicating its about complete, partial or absence devitalization after treatment.

Purpose. To evaluate the overall, disease-specific, event-free, relapse-free survival of retinoblastoma (RB) patients and cumulative probability of eye survival in such patients.Material and methods. The study included 223 children with RB (126 male, 97 female). Monolateral disease was diagnosed in 69.1 % of cases (n = 154), bilateral disease in 30.9 % (n = 69). The median follow-up was 40 months (interquartile range from 27 to 53 months). According to ABC classification, group A was diagnosed in 16 of 292 eyes (5.5 %), group B — in 53 (18.2 %), group C — in 41 (14.0 %), group D — 58 (19.9 %), and group E — in 124 (42.5 %). Group E was detected twice as often in patients with unilateral RB as in bilateral RB (56.5 % versus 26.8 %; p < 0.01). Stage T1 according to TNM classification was diagnosed in 69 cases (23.6 %), stage T2-T3 — in 213 cases (72.9 %). The extraocular form (stage T4) was detected in 3.4 % of cases (n = 10).Results. The overall five-year survival of patients treated for RB (n = 223) was 96.4 ± 1.4 %. The 5-year disease- specific survival (n = 222) was 96.8 ± 1.3 % in the general cohort, 96.5 ± 1.5 % in the group of children with monocular RB, 97.3 ± 2.7 % for binocular RB. Five-year event-free survival rate of children who received treatment (n = 223) was 66.7 ± 3.6 %, with monolateral lesion (n = 154) — 74.1 ± 4.2 %, with bilateral lesion — 50.6 ± 6.2 % (n = 69). Five-year relapse-free survival took place in 83.3 ± 3.1 %, with monolateral RB — 87.8 ± 3.3 %, with bilateral RB — 73.3 ± 6.4 %. Primary enucleation was performed in 121 of the 223 children treated for RB and included in the study. The frequency of primary enucleation with monocular RB was more than twice as high (55.2 %; 85 of 154 eyes) as with binocular RB (26.1 %; 36 of 138 eyes; p < 0.01). Organ-preserving treatment was carried out in 138 cases (171 eyes). It was effective in 123 (89.2 %) children (152 eyes; 88.9 %). 5-year ocular survival was 85.7 ± 3.7 %, with monolateral RB — 78.2 ± 6.6 %, with bilateral RB — 92.2 ± 2.8 %. Ocular survival counted separately for groups A, B, C, D, equaled 100 %, 100%, 76.6 ± 6.9 %, and 71.1 ± 11.9 %, respectively. The five-year disease-specific survival rate of children with monocular lesion given eye-preserving treatment was 100%, significantly higher than after primary enucleation — 93.4 ± 2.9 %.Conclusions. Modern combined retinoblastoma treatment is able to save the sick children’s lifes and and even their eyes and visual functions, which improves social adaptation and quality of life. It has been shown that, with a binocular form, it is possible to save more eyes than with a monocular form. Eye-preserving treatment administered to patients with intraocular RB under strictly observed criteria does not heighten the risk of metastasis. Yet timely enucleation in cases of absolute indications remains the method of choice in saving the life of a child.

Additional covering of the lower pole with allomaterial or its synthetic analogues during immediate breast reconstruction is being performed at the N. N. Petrov National Medical Research Oncology Center, Ministry of Health of Russia, for last 7 years. Initially, epidermal flap was the only option for lower pole coverage; later acellular dermal matrix was used as part of clinical approbation. Average complication rate ranges from 20–35 % due to blood circulatory (supply) disorders.Since 2018, a titanised mesh been used as an additional coverage of the lower pole in the department of breast tumors. Through coating characteristics and its structure the frequency of fatal complications significally decreased.

Biopsy of signal (sentinel) lymph nodes (LN) has been performed at the N.N. Petrov National Medical Research Oncology Center, Ministry of Health of Russia, for almost 20 years. In the first few years, contrast-visual method (1 % blue isosulfan and triphenyl methane control) was used in 640 patients with early (T1–2N0M0) breast cancer. In 150 patients from this cohort, standard axillary dissection was performed irrespectively of the results of signal (sentinel) biopsy. The rate of false positive responses varied between 4.6 and 6.6 %. Since 2012, radioisotope method of visualization of signal LN with intratumor administration of 99mТс-technephyte colloid particles has been used (in 708 patients with T1–3N0M0 breast cancer). This type of signal LN biopsy had the following diagnostic characteristics: sensitivity was 58.9 %, specificity was 96.2 %, diagnostic accuracy was 87.1 %.In parallel with this study, in 2016 a study of diagnostic accuracy and safety of biopsy of axillary LN after neoadjuvant systemic therapy was started. The study included 263 patients with T1N1–3M0, T2–3N0–3M0, T4N0–1M0 breast cancer. To evaluate clinical status of axillary LN, ultrasound, single-photon emission computed tomography, mammography at baseline and after completion of neoadjuvant chemotherapy ± targeted therapy (trastuzumab) were performed. In some patients, in the recent years a double method of signal LN labeling (radioisotope and fluorescent methods) was used.In patients with baseline cN+-status, the rate of false positive signal LN biopsy conclusions was 13.6 %, in patients with baseline cN0-status it was 7.7 %.The study of double contrast of axillary LN and targeted label of metastatic LN prior to neoadjuvant systemic therapy continues. In total, various modifications of biopsy of signal LN were performed in 2,000 patients with breast cancer.The study protocol was approved by the biomedical ethics committee of N.N. Petrov National Medical Research Oncology Center, Ministry of Health of Russia.All patients gave written informed consent to participate in the study.

The article discusses the problem of plastic environmental pollution and promising ways to solve it. One of such ways is to reduce the volume of the production of disposable plastic tableware with the subsequent transition to the use of biodegradable samples. Based on the analysis of the technological chain of disposable tableware production in Russia, a set of measures has been proposed to support its participants in the transition to the production of its substitutes (paper and biodegradable tableware).

Aim. To study lipid-lowering therapy in patients with high and very high risk of cardiovascular events (CVEs) at the outpatient and inpatient care stages in Irkutsk.Material and methods. We analyzed 260 discharge summaries of patients with hypertension of high and very high risk of CVEs for the second half of 2019: 145 — from a hospital; 115 — from outpatient records. Patient adherence to statin therapy, achievement of target lowdensity lipoprotein cholesterol (LDL-C) levels in each patient subgroup was assessed.Results. The proportion of patients who reached the recommended LDL-C levels in accordance with the 2017 guidelines tends to increase in comparison with prior data. High adherence to lipid-lowering therapy was accompanied by an increase in the proportion of patients reaching the recommended LDL-C levels. In most cases, regardless of cardiovascular risk, low-dose statin therapy were used. A detailed analysis of adherence to statin therapy using questionnaires revealed that more than half of patients in high-risk categories (64%) did not comply with lipid-lowering therapy.Conclusion. Favorable trends were revealed in relation to an increase in the proportion of high-risk patients reaching target LDL-C levels. Adherence to statin therapy remains low. Previously established problems in managing such patients remains: stereotyped lipid-lowering therapy prescriptions without taking into account cardiovascular risk, the use of low-dose therapy, and the frequent prescription of statins with a lower lipid-lowering effect. Inpatients use higher statin doses than outpatients.

The relevance of the research topic is predetermined by significant changes in the domestic and world educational space. Modernization of educational technologies, the emergence of an electronic library resource, the active use of the information and communication network Internet in the educational process expands the possibilities for the realization of the right to education, makes it accessible regardless of the place of residence and the material status of students. At the same time, the Russian regulatory and legal framework of the educational process at the higher education level is universalized for any educational programs, regardless of the form of their implementation and the educational technologies used, which results in the refusal of many higher education institutions from distance educational technologies. The article summarizes the domestic practice in the application of distance learning, analyzes the positions of the leading researchers on the issues examined. The authors offer their forecasts regarding the future development of digital technologies in the higher education segment of the Russian market of educational services. The article grounds the need to differentiate the requirements of the Federal state educational standards depending on the methods and forms of implementing educational programs, simplifying the requirements for conducting practices, current and intermediate monitoring of learning outcomes, and material and technical support when using distance higher education. Proposals are made to improve the methodological support and legal regulation of the implementation of educational programs using digital technologies.

Aim. Analysis of the results of surgical treatment in patients with epibulbar malformations. Patients and Methods. The study included 126 patients with a preliminary diagnosis of “epibulbar neoplasm”, who received treatment from January 2013 to December 2017. Male patients were 57.9 % (n = 73), female — 42.1 % (n = 53). The age range was from 6 months to 82 years (13.0 ± 11.4). All patients underwent complex ophthalmological examination and surgical treatment with histological verification of the obtained material. In case of deficiency of own tissues, when the conjunctival defect was closed, plastic was made using an amniotic membrane. Results. 67 (53.2 %) patients had a diagnosis of dermoid of the conjunctiva and / or cornea. In 14.3 % of cases, a diagnosis of lipodermoid with spreading into the eyelids fornix was established. In 7 patients there was a combined lesion, of them in 4 cases with Goldenhar syndrome, 1 case with Jadassohn syndrome and in 2 cases without syndromic disorders. In 10 patients, multicentric lesions were noted with the formation of several dermoids. Choristomas of different structures were identified in 41 patients (32.5 %). Complications of surgical treatment included limitation of eye mobility (n = 9), ptosis of the upper eyelid (n = 7), diplopia (n = 4), ocular deformity (n = 3), corneal perforation (n = 1), symblepharon (n = 1) and entropion (n = 1), which required additional surgical interventions with a favorable functional outcome. Conclusions. Diagnosis of epibulbar malformations requires a comprehensive ophthalmological examination to determine the prevalence of the process, the extent of the lesion in order to plan the timing and tactics of surgical treatment. Congenital epibulbar malformations of the eye are subject to surgical treatment with the growth of lesion, chronic inflammation, cosmetic dissatisfaction and spread to the central parts of the cornea. The use of the amniotic membrane improves normal epithelization and reduces the degree of postoperative scar deformation.

Aim. Heart failure (HF) is accompanied by skeletal muscle atrophy and exercise intolerance. The aim was to study the molecular mechanisms underlying the therapeutic effect of personalized exercise in patients with HF.Material and methods. RNA sequencing obtained from skeletal muscle biopsies before and after a 12-week exercise course was used to identify changes in gene expression and signaling pathways induced by the physical rehabilitation program for patients with HF.Results. We have shown that personalized exercise program in patients with HF stimulates the activation of molecular pathways regulating the differentiation and functioning of skeletal muscles: commitment of muscle progenitor cells; mechanisms regulating the calcium release and sensitivity of myofibrillar contraction, electrical excitability of the muscle membrane, synaptic vesicle proton gradient creation, maintenance of electrochemical gradients of Na+ /K+ . Also, the analysis of differentially expressed genes revealed an increase in the expression of transcription factors MyoD and MEF2, which are responsible for the differentiation of muscle stem cells, and sarcomeric genes MYOM1, MYOM2, MYH7. Along with this, we observed activation of the CYR61 expression — a potential prognostic biomarker for HF patients.Conclusion. Our data show that the beneficial effect of personalized aerobic exercise in patients with HF depends, at least in part, on an improvement in the physiological and biochemical parameters of skeletal muscle.

Background and Purpose. In heart failure (HF), metabolic alterations induce skeletal muscle wasting and decrease of exercise capacity and quality of life. The activation of skeletal muscle regeneration potential is a prospective strategy to reduce muscle wasting; therefore, the aim of this project was to determine if functional properties of skeletal muscle mesenchymal progenitor cells (SM-MPC) were affected by HF-induced functional and metabolic dysregulations. Methods. Gastrocnemius muscle biopsy samples were obtained from 3 healthy donors (HD) and 12 HF patients to purify mRNA for further analysis and to isolate SM-MPC. Cells were expanded in vitro and characterized by immunocytochemistry and flow cytometry for expression of mesenchymal (CD105/CD73/CD166/CD146/CD140b/CD140a/VIM) and myogenic (Myf5/CD56/MyoG) markers. Cells were induced to differentiate and were then analyzed by immunostaining and Q-PCR to verify the efficiency of differentiation. The expression of genes that control muscle metabolism and development was compared for HD/HF patients in both muscle biopsy and in vitro-differentiated myotubes. Results. The upregulation of MYH3/MYH8/Myf6 detected in HF skeletal muscle along with metabolic alterations indicates chronic pathological activation of the muscle developmental program. SM-MPC isolated from HD and HF patients represented a mixed population that coexpresses both mesenchymal and myogenic markers and differs from AD-MMSC, BM-MMSC, and IMF-MSC. The functional properties of SM-MPC did not differ between HD and HF patients. Conclusion. In the present work, we demonstrate that the metabolic and functional alterations we detected in skeletal muscle from HF patients do not dramatically affect the functional properties of purified and expanded in vitro SM-MPC. We speculate that skeletal muscle progenitor cells are protected by their niche and under beneficial circumstances could contribute to muscle restoration and prevention and treatment of muscle wasting. The potential new therapeutic strategies of HF-induced skeletal muscle wasting should be targeted on both activation of SM-MPC regeneration potential and improvement of skeletal muscle metabolic status to provide a favorable environment for SM-MPC-driven muscle restoration.

Brain metastases are detectable in 25–35 % of patients with progressive HER-2-positve breast cancer. Even after spreading metastases into the brain, chemotherapy in combination with anti-HER- 2 therapy improves survival due to better control of the systemic disease. The paper presents the results of investigations substantiating the use of anti-HER-2 targeting agents, as well as the innovative agent T-DM1 to treat brain metastases.

Objective: to determine the ratio of different types of state and public control in the sphere of higher education and to propose an optimal model of their interaction. Methods: systemic-structural approach to the analysis of the research object, comparative-legal and logical methods. Results: basing on the regulatory framework analysis, licensing procedures, state and public accreditation of basic educational programs in the field of higher education, critical consideration of the main directions of state policy in the sphere of education, the authors summarize the educational reform, make proposals on improving the legal tools in the sphere of higher education control and supervision in the Russian Federation. Scientific novelty: for the first time, the different parameters of the state and public control in the sphere of higher education were comprehensively examined in the context of compliance with the principles of state management. Practical value: basing on the study of the theoretical foundations and practical examples, the authors make proposals to improve the existing legislation regulating relations in the sphere of state and public control of higher education.

Relevance. The development of antimicrobial drugs and alternative methods, technologies and means of prevention, diagnosis and treatment of human infectious diseases caused by antibiotic-resistant microorganisms is one of the priorities of ensuring the biological safety of the country. Aims. To evaluate the bactericidal activity of tetrapyrrole macroheterocycles (porphyrins) at different light irradiation durations in relation to staphylococci, in vitro. Materials and methods. Studied strains of microorganisms: museum strains of microorganisms – S. aureus ATCC 29213, S. epidermidis ATCC 14990 and antibiotic-resistant strains of bacteria of the genus Staphylococcus (n=18) isolated from clinical biomaterial and from environmental objects in a medical organization. The studied chemical compounds are three different compounds of water-soluble asymmetrically substituted porphyrins containing heterocyclic fragments on the periphery of the porphyrin cycle (residues of benzoxazole, N-methylbenzimidazole and benzothiazole). Results. The activity of all three porphyrin compounds in relation to museum strains of staphylococcus and 77.8% of clinical antibiotic-resistant strains (n=14; 95% CI 20.1-97.5) turned out to be maximal (complete lysis) after 10 minutes of irradiation. Conclusions. The tested tetrapyrrole macroheterocycles (porphyrins) exhibit bactericidal activity against museum and clinical strains of staphylococcus, with different levels of antibiotic resistance, which determines Keywords: antibiotic resistance, water-soluble porphyrin, photodynamic inactivation, photosensitizer, photochemistry, staphylococci No conflict of interest to declare.

The aim of the work was to study the species diversity of pathogenic and non-pathogenic hantaviruses circulating in populations of small mammals in the Republic of Bashkortostan using molecular-genetic methods.Materials and methods. Individual samples from small mammals were tested by the nested PCR using genus-specific primers that amplify the L segment of hantaviruses. The resulting PCR products were sequenced by the Sanger’s method from internal nested PCR primers. For samples containing Puumala virus, fragments of the S, M, and L segments of the viral genome were sequenced using Sanger’s method. The construction of phylogenetic trees was carried out using the MEGA X software.Results and discussion. Out of 300 examined samples of small mammals collected on the territory of the Republic of Bashkortostan in 2023, 14 samples have been found positive for the presence of hantavirus RNA: Seewis (8), Tula (3), Puumala (3). The circulation of the non-pathogenic hantavirus Seewis and the opportunistic hantavirus Tula has been established for the first time in the Republic of Bashkortostan. The circulation of the Seewis hantavirus has been confirmed in populations of the common shrew (Sorex araneus) and the pygmy shrew (S. minutus); the Tula hantavirus – in populations of the common vole (Microtus arvalis). Results of phylogenetic analysis substantiate the reassortment origin of one of the genetic variants of the Puumala hantavirus on the territory of the Republic of Bashkortostan. The prerequisites for the formation of combined natural foci of hantaviruses Puumala, Seewis, and Tula on the territory of the Republic of Bashkortostan are discussed.

Questionnaire of 285 teachers of comprehensive schools estimated subjective fatigue and possibilities of restoration of working capacity depending on a number of biological and. social factors. From among studied factors the greatest contribution to efficiency of workers of brainwork is brought by indicators of a state of health, in particular chronic incidence, frequency of diseases in a year and. value judgment of health. The age of the worker and. level of satisfaction of the general and. professional requirements have a certain value.

The role of the professional factor in subjective satisfaction of the basic vital needs (by Mazhnikova N.V. et al., 2001) and frequency of an arterial hypertensia at 791 workers of the enterprises and establishments was studied. It is shown that conditions of labor activity cause distinctions as the general, and separate types of satisfaction of requirements that associates with various level of frequency of an arterial hypertensia.

The analysis of possibilities of forecasting of an arterial hypertensia depending on age and character of professional work of 607 women of mass trades is carried out. It is shown that groups of the raised and high risks of development of an arterial hypertensia make women is more senior 40 years, working in the trades characterised by physical work, and also brainwork.

Adaptation level of pregnant women having iron deficiency anemia and gestation hydremia was studied using the analysis of white blood formula. It is proved that in gestation anemia, disadaptation can be seen most frequently at the first half of pregnancy and in the period of 29-32 weeks of gestation. In iron deficiency anemia, the most high strain of adaptation systems is recorded in the period of 20 to 32 weeks of pregnancy. It points to different directions of adaptive reactions in iron deficiency anemia and gestation hydremia, which are united by the decrease of hemoglobin level in pregnant women needs differentiation of correction of abovementioned states.

Relevance. During and after the COVID-19 pandemic, viruses have become a more common cause of pulmonary infections in adults; therefore, the distinction between viral lung injury and community-acquired bacterial pneumonia is of increasing importance. Aim. Development of a model for differentiating community-acquired bacterial pneumonia and viral lung injury, including COVID-19. Materials and methods. This retrospective case–control study included 300 adult patients with viral lung injury and 100 adult patients with community-acquired bacterial pneumonia. Clinical, laboratory, and instrumental data were analyzed, significant factors were selected by which the samples differed, and a model was developed using logistic regression to distinguish between community-acquired bacterial pneumonia and viral lung damage, including COVID-19. Results. The developed model included the following parameters: total protein level, neutrophil/lymphocyte index, heart rate, unilateral infiltration on CT or chest x-ray, vasopressor prescription in the first 24 h of hospitalization, altered level of consciousness, chills, and fatigue. The model had the following characteristics: AUC = 0.94 (0.92–0.96), AUC_PR = 0.84 (0.76 to 0.92), prediction accuracy — 90%, sensitivity — 76%, specificity — 95%, positive predictive value — 83 %. Conclusion. The use of this model can facilitate the differential diagnosis of community-acquired bacterial pneumonia and viral lung injury, including COVID-19, in adults in general wards and intensive care units.

The aim of the work was to conduct an analysis of the current state and current trends in the approval of drugs, as well as some aspects of the methodology for their development based on biological molecules and registration.Materials and methods. The material for the analysis was taken from the abstract databases of PubMed, Google Scholar and e-library.ru. The search was carried out using publications for the period from 2008 to 2023, the keywords were as follows: “biologicals”, “new drug approval”, “drug authorization”, “drug development”, “biosimilar”, taking into account various spellings.Results. Over the past 15 years, scientists have been observing revolutionary trends and processes in the field of the drug development, especially biopharmaceuticals. Significant advances have been made in gene, immune and cell therapies, resulting in the approval of such drugs more than doubling over the past ten years. The development of biological drugs includes the identification and testing of molecular targets and requires a deep understanding of the structure and functioning of the polypeptides involved in the development of the effect. The features of these active pharmaceutical substances are a high molecular weight, a complex three-dimensional structure and a high immunogenic potential. Preclinical and clinical studies of biologics have unique challenges. Selecting appropriate animal species, understanding the immunogenicity, and assessing pharmacodynamics and toxicological properties require a multilevel, detailed approach. The article discusses the regulatory framework under which these drugs are registered, summarizing the guidelines provided by international organizations such as the International Council for Harmonization and various national agencies.Conclusion. The analysis highlights the current advances and prospects in the development of biologics, highlighting their key role in future transformations in the treatment of rare diseases and oncology, approaching the era of personalized medicine. Monitoring the development directions and technological approaches, as well as the commitment to global methodological and regulatory aspects can become a catalyst in the development of the Russian pharmacology.

Modern approaches to the treatment of type 2 diabetes mellitus (T2DM) are aimed not only at glycemic control, but also at reducing cardiovascular risks. The increasing prevalence of the disease and the need for effective treatment options highlight the importance of glucagon-like peptide-1 (GLP-1) receptor agonists in the pharmacotherapy structure.The aim of the work was to review the literature regarding the physiology of GLP-1 and the therapeutic potential and development trends of its agonists.Materials and methods. The search for the review materials was carried out using the abstract databases of PubMed, Google Scholar and e-Library. The search was carried out for publications from 2000 to 2023, using the following keywords: “GLP-1”; “GLP-1R agonists”; “GIP”; “exenatide”; “liraglutide”; “dulaglutide”; “semaglutide”; “lixisenatide”; “albiglutide”; “taspoglutide” taking into account various spellings.Results. The interaction of almost all food components with enteroendocrine cells of the intestine leads to the secretion of incretins (primarily GLP-1) into the blood, triggering a complex of physiological reactions aimed primarily at the rapid utilization of incoming glucose (regulation of insulin and glucagon secretion), as well as the central regulation of dietary behavior (slowing gastric emptying and the formation of a feeling of satiety). A wide distribution of the GLP-1 receptor in various tissues and organs, its connection with intracellular signaling cascades aimed at launching energy-consuming remodeling (recovery) processes in endothelial cells, heart, neurons, beta cells, etc., is the basis for a wide range of pleiotropic effects of GLP-1 unrelated to its hypoglycemic effect. The discovery of synthetic GLP-1 receptor agonists with a long period of action has made it possible not only to therapeutically influence various parts of carbohydrate metabolism disorders, but also to increase the functional reserves of the target diabetes organs, reducing the risk of developing complications of the disease. Incretin-like drugs are well tolerated, with nausea being the most common side effect. The factors limiting a wider use of the drugs include their high cost and the preferred form of a subcutaneous solution. The current research is focused on the development of long-acting, oral, dual and triple agonists, fixed-dose combinations, and small molecule drugs.Conclusion. GLP-1 receptor agonists are a class of effective and safe drugs for the treatment of diabetes and obesity, which is rapidly developing in the most advanced areas of pharmacy. A further development of this group and the solution of the identified problems will open up new opportunities for the treatment of diabetes and its complications.

Objective: study of the relationship between arterial hypertension and arterial stiffness in women to identify potential markers of target organ damage and therapeutic targets of antihypertensive therapy.Materials and methods: the study involved 161 women who were divided into three groups depending on age and reproductive function. Group 1 consisted of 52 women aged 18 to 30; group 2 – 54 women aged 31 years before menopause; 3rd group – 55 women in the postmenopausal period. All women were questioned, clinical examination, determination of anthropometric data, measurement of carotid-femoral pulse wave velocity, determination of arterial stiffness by volumetric sphygmography, 24-hour blood pressure monitoring with assessment of aortic stiffness and characteristics of the central pulse wave.Results: 24-hour blood pressure monitoring revealed arterial hypertension in 38 (34,8%) women: 15 (27,8%) women in the 2nd group and 23 (41,8%) women in the 3rd group. Correlation analysis revealed the most significant correlations between the presence of arterial hypertension (R=0,45-0,71; p<

Acute flaccid myelitis is a syndrome characterized as the development of acute flaccid paralysis of one or more limbs due to lesions of the anterior horns of the spinal cord, which occurs against the background of a viral infection. More than 300 acute flaccid paralysis cases are registered in the Russian Federation annually, most of them are of a non-infectious etiology. In some cases, patients develop a complex of symptoms similar to poliomyelitis, but without isolation of polioviruses from stool samples. Clinical characteristics of such cases include acute onset, fever, persistent peripheral asymmetric paresis/paralysis of predominantly proximal parts of the limbs, and absence of pathological reflexes, pelvic disturbances, or pyramidal symptoms. In literature, such complex of symptoms is referred as acute flaccid myelitis. We provide an analysis of 18 cases of acute flaccid myelitis detected in the Russian Federation in the period from 2015 to 2019. A clear seasonality of the disease from July to November was noted. Studies of faecal samples, cerebrospinal fluid and blood samples did not reveal the pathogen. In all patients, regardless of therapy, there was a positive trend, but complete recovery was not achieved: paresis of varying severity persisted, mainly in the proximal extremities Therefore, acute flaccid myelitis cases as acute flaccid paralysis cases of unknown etiology require an additional observation and an expanded algorithm of laboratory investigation aimed to finding a possible pathogen.

The yield and quality parameters of potato tubers of Gala variety were determined in the conditions of the Middle Urals in 2020 and 2022 in long-term stationary experiment after prolonged application of NPK increasing rates (30-60-90-120-150 kg a.i.). The application of NPK by 60 kg a.i./ha and more promoted the potato yield raise by 1.1-1.3 times in 2020 and by 1.3-1.5 times in 2022 compared with the control variant without fertilizers (21.4 and 14.4 t/ha by years, respectively). The lowest dry matter content over the years of research was noted at the maximum dose of N150P150K150 mineral fertilizer in the experiment– 15.6 % in favorable weather conditions of 2020 and 19.4 % in the dry 2022. The starch content in potato tubers did not depend on the dose of applied mineral fertilizers and varied in 2020 in the range from 11.1 to 13.8 %, in 2022 – from 14.4 to 16.3 %. In potato tubers the content of crude protein in the wet mass increased from 1.32 to 1.90 % in 2020 and from 1.80 to 2.65 % in 2022 to the weight of wet mass with an increase in the dose of NPK from 30 to 150 kg/ ha active substance. The sugar content in 2020 was 0.58-0.83 % for natural humidity, in 2022 – 0.23-0.47 %. The fiber content in potato tubers did not depend on the doses of applied mineral fertilizers. The application of increasing doses of NPK did not lead to exceeding the permissible value of the nitrate content in fresh potato. According to a comprehensive assessment of the quality of tubers, potato yield, obtained under given conditions, was suitable for the production of low carbohydrate potato products and for fodder purposes.

Aim. To assess the possibility of familial hypercholesterolemia (FH) detection among patients with early coronary artery disease (CAD) in practice in comparison with data from different populations. Patients with early manifestations of CAD are a promising group for identifying a proband with FH and subsequent cascade screening. The question remains open about the sufficiency of clinical criteria for diagnosing this disease.Material and methods. We examined 651 patients with CAD manifestations aged £55 years in men and £60 years in women. FH was diagnosed according to the Dutch Lipid Clinic Network (DLCN) criteria, and cardiovascular risk was assessed using the Montreal-FH-SCOR E. In 35 phenotype-positive patients with FH, as well as 5 with lowdensity lipoprotein cholesterol levels ³5,5 mmol/l and 23 with age of manifestation of coronary artery disease £35 years, the coding sequence of the genes for apolipoprotein B (APOB), low-density lipoprotein receptor (LDLR), low-density lipoprotein receptor adapter protein 1 (LDLRAP1), proprotein convertase subtilisin/kexin type 9 (PCSK9).Results. Definite FH was in 8 (1,2%), probable in 27 (4.2%), possible in 339 (52,1%) patients, while 277 (42,5%) patients had DLCN score of

Interferon inducers are of interest as the first line of defense against viral infections, including influenza. Double-stranded ribonucleic acid (dsRNA) for intranasal administration has been developed, the excipients and drug components were selected at the Institute of Medical Biotechnology, a branch of the State Research Center of Virology and Biotechnology «Vector». This work presents the results of the study on antiviral activity and pharmacological safety of a new form of dsRNA. The antiviral activity of the preparation was studied in BALB/c mice infected with influenza A/Aichi/2/68 (H3N2) or Bishkek/01/2009 (H1N1pdm09) viruses. A safety study was performed with a single administration of intranasal dsRNA into white outbred ICR mice. The study showed that the administration of therapeutic and prophylactic regimen of intranasal dsRNA at a dose of 2.5 mg/kg increases the survival and average life expectancy of mice infected with the mentioned strains of influenza virus. The protective effect of the preparation in mice infected with a lethal dose of Bishkek/01/2009 virus was comparable to the effect of Tamiflu. The absence of toxic effects of intranasal dsRNA at a pharmacological dose in laboratory mice, the functional state of their physiological systems, as well as main types of metabolism, established in the experiments, lead to a conclusion concerning pharmacological safety of the preparation and the prospects for further work to complete pharmaceutical development of a new antiviral drug.

Introduction. The solubility of an active pharmaceutical ingredient plays a major role in drug absorption. Hot melt extrusion is a batch or continuous process that allows creating solid dispersion systems based on various carriers in order to increase solubility and bioavailability of active substances. Development of effective and safe analgesics is one of the most vital tasks of organic and medicinal chemistry. An innovative non-opioid analgesic with very low toxicity and low dosage, but practically insoluble in water, was used in this work. It was suggested to obtain a solid dispersion by hot melt extrusion in order to increase bioavailability.Aim. Development a hot melt extrusion technology for production of a solid dispersion system of PAV-0056 as an active substance and Plasdone™ S-630 as a polymeric carrier to increase the solubility.Materials and methods. PAV-0056 (methyl-2-(7-nitro-2-oxo-5-phenyl-3-propoxy-2,3-dihydro-1H-benzo[e][1,4]diazepin-1-yl)acetate) (JSC "Organica", Russia) Figure 1; Plasdone™ S-630 (Boai NKY Pharmaceuticals Ltd., China); PEG-1500 (Clariant, Switzerland); acetonitrile for chromatography (Thermo Fisher Scientific, Germany). Extrudates were obtained using a HAAKE™ MiniCTW co-rotating twin-screw laboratory extruder (Thermo Fisher Scientific, Germany). Extrudates were examined by optical microscopy and differential scanning calorimetry, and time of water solution stability was determined. The quantitative content of the active substance and related impurities in the 2.5 % solid dispersion of PAV-0056 was determined by HPLC-UV.Results and discussion. Hot melt extrusion process conditions were established for a mixture of 2.5 % PAV-0056 and Plasdone™ S-630. Stability of the extrudate solution in water was studied, the content of the active substance and impurities in the extrudates was determined. Based on the binary mixture, a composition containing 10 % of PEG-1500 was developed. The optimal conditions for the extrusion process were chosen for obtaining a solid dispersion system that meets the requirements of the regulatory documentation for the content of the active substance and impurities.Conclusion. The binary mixture proved to be unsuccessful for the creation of SDS by hot melt extrusion due to significant accumulation of impurities during the extrusion process. By adding PEG-1500 to the composition, it was possible to considerably lower the operating temperature of the process, reduce the impurity content in the extrudate, and maintain satisfactory stability of the PAV-0056 solution in water.

In the presented case report, a patient with persistent atrial fibrillation developed due to borreliosis and grade III left atrial spontaneous echo contrast (SEC) according to transesophageal echocardiography, in order to rule out intracardiac thrombosis and concomitant Lyme carditis, contrastenhanced cardiac magnetic resonance imaging was performed. Given the rapid progression of heart failure on the background of tachycardia, the lack of evidence for left atrial appendage thrombosis and myocarditis, electrical cardioversion was performed with the restoration of sinus rhythm and without thromboembolic complications during further follow-up. The issues of the clinical and prognostic significance of SEC, the potential of various diagnostic methods, and the management of such patients are discussed.

Background: More than 125 million (2%) people worldwide wear contact lenses (CL). Rates of CL-associated infections increase with an increase in frequency of wear of CL. Purpose: To compare the bacterial and fungal microflora of the conjunctiva and contact lens in therapeutic soft contact lens (SCL) wearers. Material and Methods: We examined the microflora of the conjunctival surface in 80 therapeutic SCL wearers and of the SCL surface in 235 relevant lenses. Monthly therapeutic SCLs that were discarded after being replaced were sent for bacteriological and mycological culture. We used only the data for the years 2016 through 2019 in the analysis. Results: Pathogenic and/or opportunistic agents were found in samples from 121 SCL (51.5%). Gram positive, Gram negative and fungal species were found in 63.5%, 29.5%, and 7.0%, respectively, of the 121 SCL. Mixed microflora was evident in 14.1% of the 121 SCL. Organisms were isolated from the conjunctiva of 51 (63.8%) of 80 patients. Gram positive, Gram negative and fungal species were found in 75.0%, 20.0%, and 5.0%, respectively, of patients. Mixed microflora was evident in 14.1% of patients. Conclusion: Organisms were isolated from the conjunctiva of 51 (63.8%) of 80 therapeutic SCL wearers and from 121 (51.5%) of 235 SCL (p = 0.06). Conjunctival swabs and SCL swabs harbored pathogenic microorganisms on 26.2% and 26.9% of occasions, respectively. On 32.5% of occasions, there was a difference in species isolated from conjunctival swabs and SCL swabs. This stresses the need for microbiological studies of the conjunctiva and contact lenses in SCL wearers.

Introduction. The only currently available live vaccine against yellow fever (YF) based on chicken embryos infected with an attenuated 17D strain of the YF virus is one of the most effective vaccine preparations. However, the live vaccine is associated with “viscerotropic syndrome” (approximately 0.4 cases per 100 000 vaccinated). Therefore, the development and introduction of highly purified inactivated vaccine against YF is intended to ensure the maximum safety of vaccination against one of the most common human viral diseases. Goals and objectives. Development and evaluation of immunogenicity of the cultural inactivated vaccine against YF at the laboratory model level. Material and methods. Adaptation of 17D strain of YF virus to Vero cell culture, cultivation, removal of cellular DNA, inactivation with β-propiolactone, concentration, chromatographic purification, determination of protein and antigen of YF virus, assessment of immunogenicity in mice in parallel with commercial live vaccine. Results and discussion. Immunogenicity: the determination of specific antibodies of class G (IgG) and virus neutralizing antibodies in the sera of immunized mice showed high level of antibodies exceeding that of immunized with commercial live vaccine. The optimal dose of antigen in the vaccine (total protein) was 50 μg/ml (5 μg/0.1 ml -dose and volume per 1 vaccination of mice). Thus, the laboratory version of cultural inactivated vaccine against YF is as effective (and even superior) as the commercial live vaccine. Conclusion. Laboratory version of cultural inactivated vaccine against YF, which is not inferior in immunogenicity (in animal model) to commercial live vaccine, has been developed.

The problems of prophylaxis of infectious complications in the treatment of oral local mucinous carcinoma are considered relevant to 204 respective cases. More favourable results of the combined and complex treatment of the patients were shown when a multidisciplinary approach was used with obligatory participation of stomatologists. Special stomatologic prophylactic and therapeutic procedures with using reamberin orally and intravenously in the chemo- and radiotherapy and adequate antibiotic therapy during the surgical operation resulted in less frequent infectious complications, that was in favour of the patients life quality. Intraosteal administration of antibiotics was shown preferable.

Introduction. The well-known advantages of class Y antibodies (IgY) from egg yolks of immunized hens in comparison with class G antibodies (IgG) of laboratory animals traditionally used in laboratory diagnosis of infectious diseases determine the stable interest of researchers in using IgY for these purposes (IgY technology) . Over the past 20 years, the obvious benefits of IgY technology have been demonstrated for a number of viral and bacterial infections. Goals and objectives. Construction of ELISA systems based on specific IgY for laboratory diagnosis of infections caused by tick-borne encephalitis virus, yellow fever virus, poliovirus. Material and methods. Obtaining yolk preparations of immunized chickens, obtaining highly purified IgY preparations (salting out, affinity chromatography), constructing ELISA systems for determining virus-specific antigens, testing the parameters of ELISA systems. Results and discussion. For the first time in laboratory practice, ELISA systems based on the use of specific polyclonal IgY were designed for laboratory diagnosis of topical human viral infections caused by flaviviruses and enteroviruses: determination of antigens of tick-borne encephalitis virus, yellow fever virus, 3 types of poliovirus. It was experimentally shown that these ELISA systems have high sensitivity and specificity, which allows them to be used for the semiquantitative and quantitative determination of antigens of these viruses in various materials (infected cell cultures, vaccines, etc.). Conclusion. The ELISA systems developed on the basis of specific IgY for determination of viral antigens can be effectively used for laboratory diagnosis of a number of viral infections, for the validation and control of vaccine preparations.