Search

The effect of 30-day dark deprivation (light-dark cycle 24/0 h, artificial illumination 300 Lux) on the morphofunctional state of the testes was studied using morphological and morphometric analysis of histological preparations of white mongrel male rats 4 months of age. The level of follicle-stimulating hormone in blood serum was assessed by enzyme immunoassay. It was found that 30-day dark deprivation increases the level of follicle-stimulating hormone in the blood serum. Morphological changes in the testes were characterized by a decrease in the area of Sertoli cells and their nuclei, the thickness of the spermatogenic epithelium. The hormonal background and morphofunctional state of the testes were corrected by the administration of exogenous melatonin for 14 days.

Primary ciliary dyskinesia (PCD) is an orphan disease associated with mutations in several genes. It is a ciliopathy, an abnormality of the cilia and flagella. Ciliopathies include the extremely rare Simpson - Golabi - Bemel syndrome (SSGB) type II.The aim of this article is to familiarize the reader with the possibility of simultaneous presence of type II SSGB and PCD in a patient with bronchiectasis (BE).Results. The first clinical observation in the Russian literature is presented withhistory, physical examination, including clinical and morphologic examination, results of additional investigations and initiation of therapy. The case describes a 15-year-old patient with BE and other lesions typical of PCD confirmed on the basis of structural changes in the cilia of the respiratory epithelium of the trachea detected by transmission electron microscopy. The patient had a pathogenic mutation of the OFD1 gene responsible for the development of both type II SSGB and PCD.Conclusion. Several variants of ciliopathies may occur in one patient, and PCD may present as a syndrome.

The article discusses the architectonics of the socio-cultural space of the city. The relevance of the work is due to the modern processes of changing the socio-cultural space in general and the city in particular. Transformations are caused by a variety of interrelated factors, such as the intensification of the urbanization process; the layering of various spaces; the influence of the economic and environmental situation in the region; migration processes. The author, relying on a comprehensive methodology, seeks to present the urban space as an integrative whole, including subject and semantic fullness, to identify the features of its transformation. The analysis of the socio-cultural space of the city is based on the study of the space of the city of Chita, its correlation with the factors contributing to the emergence of this space and the reasons transforming it. The author notes the great importance of Chita of the historical past for the formation of urban space. To change the appearance of the socio-cultural space of the city.

Huntington’s disease is a serious inherited neurodegenerative disorder characterized by of motor, cognitive and psychiatric features. The disease is caused by an abnormally expanded CAG repeat expansion in the HTT gene and the production of mutant huntingtin protein.The disease usually manifests in adulthood, but the manifestation in childhood and youth is also described, which is noted in 5–10 % of cases. The disease predominantly affects the neostriatum, resulting in a characteristic clinical picture.The most promising approaches to etiotropic therapy of Huntington’s disease are a number of DNA- (CRISPR/Cas9 system) and RNA-directed methods (antisense oligonucleotides, RNA interference), methods that directly reduce the level of mutant gentingtin (chimera molecules), as well as approaches based on inactivating the DNA mismatch repair system using the FAN1 enzyme.

There are the results of a study of the factors determining the formation and changes in the filtration properties of a heap leaching stack formed from pelletized poor sandy-clay ores. An analysis of methods of investigation of filtration properties of ore material for different stages of heap leaching plots functioning is carried out. Influence of segregation process during stack dumping on formation of zones with very different permeability parameters of ore has been established by experimental and filtration works. The construction and application of a numerical model of filtration processes in pelletized ores based on laboratory experiments is shown. By means of solution percolation simulation at different irrigation intensities the justification of optimal stack parameters is provided in terms of the geomechanical stability and prevention of solution level rise above the drainage layer.

Objective of the study: To review worldwide literature data on the efficacy of combined modality treatment including intraoperative radiation therapy (IORT) in patients with operable breast cancer (BC). Material and Мethods. Of 110 publications (2000–2021) available from Scopus, Pubmed, Elibrary and other databases, using the key “breast cancer”, “local recurrence”, “intraoperative radiotherapy” and “radiation technique”, 45 were included in the literature review. Results. Radiotherapy is of paramount importance in the organpreserving treatment of breast cancer, as numerous randomised studies have shown that the use of postoperative radiotherapy dramatically reduces the number of locoregional recurrences. The use of IORT as an effective method of relapse prevention compared to standard postoperative adjuvant radiotherapy is an important trend in radiation oncology.Conclusion. The use of IORT in combination treatment modality for operable breast cancer should be differentiated and based on clinical and morphological prognostic factors. Different molecular subtypes of breast cancer are characterized by significant differences in pathogenesis and response to therapy. Further studies on the effectiveness of IORT are required to identify a group of patients with absolute indications for the use of IORT.

To prevent fractures which the elderly and the very old might deal with is a strategic task for preserving the life quality of the elderly and their independence from outside help, as well as reduce the health care and social support economic costs. The most effective and cost-effective organizational structure for reducing fractures frequency is the Fracture Liaison Service (FLS). The foundation of FLS at the regional level includes various models of these services, which is associated with a multi-level system of trauma care, different numbers of attached population and different number of specialists. Firstly, these are identification, assessment of clinical risk factors for osteoporosis, investigation for secondary osteoporosis causes and treatment initiation in the FLS with follow-up in the primary health care in 12–18 months’ time. Secondly, these are identification, risks assessment, patients’ investigation in the FLS during 3 months with the follow-up treatment initiating by the primary health care physician. And thirdly, these are assessment, investigation and treatment initiation by a primary care doctor immediately after trauma care. In any case of the FLS organization, a patient who has had a fragility fracture in any period after the fracture will be under the supervision of a primary care physician, and therefore additional efforts should be made by healthcare organizers, heads of a medical organization and other specialists in order to increase the identification of the patients with osteoporosis, their examination and treatment with anti-osteoporotic drugs in the primary health care. The article presents the results of the studies confirming the effectiveness of FLS with a coordinator, educational activities for patients and doctors, the role of a traumatologist in motivating a patient for examination and treatment, and other options to help a primary care physician with identifying, diagnosing and treating patients after fragility fractures.

Introduction. Biological characteristics of the tumor play a major role in it’s development and progression. Currently, using the molecular markers aimed at resolving the problems in clinical oncology is becoming more important, including thyroid carcinomas. Heterogeneous contradictory data had been accumulated to date showing the ability of tumors genetic and biological parameters to predict the diseases outcome.Aim. To investigate prognostic value of transcription, growth factors, components of AKT / mTOR signaling pathway and autophagy protein LC3B in patients with papillary thyroid cancer in relation to recurrences and overall survival.Materials and methods. The study included 65 patients with T1–4N0–1M0 papillary thyroid cancer. According to the criteria of the American Thyroid Association (ATA) (2015), patients were divided into groups of patients with high, low and intermediate risk. 30 patients were classified as low risk, 23 as intermediate risk, and 12 as high risk. The BRAFV600 mutation was identified in 18 samples. The expression of transcription factors (p65 and p50 subunits of nuclear factor kappa B (NF-κB p65, NF-κB p50), hypoxia-inducible factor 1 (HIF-1), hypoxia-inducible factor 2 (HIF-2), growth factors (vascular endothelial growth factor (VEGF), receptor VEGF (VEGF-2), carbonic anhydrases of type 9 (CAIX)), AKT, c-RAF, GSK- 3β, p70S6, mammalian target of rapamycin (m-TOR), PDK, PTEN, 4E-BP1 in the tumor was assessed by real-time polymerase chain reaction (PCR). The BRAFV600 mutation was investigated using real-time allele-specific PCR. The content of the LC3B protein was examined using the Western Blot method.Results. As a result of the study, there is an increase in c-RAF expression with an increase in risk from low to high, which was accompanied by a decrease in 4E-BP1 expression. c-RAF mRNA levels were increased 3.0- and 2.8‑fold in the intermediate and high-risk groups, respectively, compared to low risk patients. There is a change in the expression of Brn-3α depending on the relapse risk. The maximum mRNA levels were found in patients with intermediate risk, where the figure was 4.3 and 6.2 times higher than in patients with low and high risk, respectively. An increase in LC3B expression by 56.0 and 28.0 times was shown in the tumor tissue of patients with intermediate risk compared with patients with low and high risk. This fact corresponds with an increasing content of the protein itself, which was higher in patients with intermediate risk. Patients with a negative BRAF gene status had an intermediate and high risk of tumor recurrence. The prognostic significance of the estrogen receptor β (ER-β) and NF-κB p50 expression level had been revealed in relation with relapse-free and overall survival of patients with papillary thyroid cancer.Conclusion. As a result of the study, additional molecular markers were found in order to for predict the tumors recurrence risk. The study showed the significance of ERβ and NF-κB p50 expression levels for predicting disease outcomes.

On the model of premature aging induced by 30-day dark deprivation (light-dark cycle 24/0 h, artificial illumination 300 Lux), the effect of exogenous melatonin (0.3 mg/kg, 14 days after the cancellation of dark deprivation, intragastric daily in 2 % starch mucus) on the dynamics of body weight and the level of Klotho protein in the blood was studied in outbred white male rats of 4 months of age. It has been shown that prolonged dark deprivation is accompanied by a statistically significant decrease in the content of the Klotho protein in the blood serum, which is a marker of premature aging. Metabolic disorders associated with a statistically significant decrease in the level of melatonin and Klotho protein in the blood were expressed in fLuctuations in the dynamics and rate of body weight gain in animaLs. At the same time, exogenous meLatonin had a protective effect on the condition of animals - it contributed to an increase in the content of Klotho protein in the blood serum and restored the level of melatonin to the values of the negative control indicator.

The rapid development of technology has a significant impact on the daily life of a person. Light, sound, information pollution leads to sleep disturbance, which has a negative impact on the physical condition. Even short-term sleep disturbance caused by dark deprivation Leads to a decrease in serum testosterone LeveLs. The imbaLance of maLe sex hormones, the synthesis of which is under the controL of the hypothaLamic-pituitary system, negativeLy affects the morphofunctionaL state of the testes. The effect of exogenous meLatonin on the morphoLogicaL and functionaL state of the spermatogenic epitheLium of the testes, Leydig cells in white outbred male rats of 4 months of age was studied on the model of premature aging caused by 30-day dark deprivation, and the KLotho protein LeveL in bLood serum was assessed by enzyme immunoassay. It was found that the morphoLogicaL changes in the testes were characterized by a decrease in the thickness of the spermatogenic epithelium by 30 days after dark deprivation and a decrease in the LeveL of the KLotho protein, which is a marker of premature aging. The introduction of exogenous meLatonin had a protective effect on the morphoLogicaL and functionaL status of the testes of animaLs, accompanied by the restoration of the spermatogenic epitheLium, an increase in the KLotho protein to the LeveL of the negative controL group.

Aromatic L‑amino acid decarboxylase (AADC) deficiency is rare autosomal recessive neurometabolic disorder. It caused by generalized combined deficiency of serotonin, dopamine, norepinephrine and adrenaline. This disorder is characterized by muscular hypotonia, motor development delay, oculogyric crises and impairment of the autonomic nervous system.Laboratory diagnostic of AADC deficiency in Russian Federation includes determination of the concentration of 3‑O‑methyldophamine in dried blood spots by tandem mass spectrometry and molecular analysis of the DDC gene by Sanger sequencing or next generation sequencing.Therapy of AADC deficiency includes combination of drugs which increase the formation of dopamine, inhibit its reuptake and increase the residual activity of the enzyme. The first‑line drugs are selective dopamine agonists, monoamine oxidase inhibitors of type B and vitamin B6 supplements.We present the case of management and treatment of patients with AADC deficiency. The patient’s condition was improved by using of combination therapy with pyridoxal‑5‑phosphate, pramipexole and selegiline. Significant positive dynamics was achieved on pyridoxal‑5‑phosphate therapy for the first time.

The synthesis of MAX phase Ti2AlN from several mixtures of Ti, Al, TiN, and AlN powders by vacuum sintering of greensamples in the form of dense compacts, bulk powder in silica tubes, and plain layer in a closed rectangular molybdenum boat was studied upon variation in charge composition and sintering temperature Ts. The sintering of 2 : 1 Ti–AlN mixture was carried out at 1100, 1200, 1300, 1400, and 1500 °С with exposure time of 60 min. The largest MAX phase content (94 wt.%) was reached at Ts = 1400 °С. The sintering of 1 : 1 TiAl : TiN composition at the same temperature gave 93 wt.% Ti2AlN. The best result (singlephase Ti2AlN in a 100-% yield) was achieved upon the sintering of 1 : 1 : 1 Ti–Al–TiN composition at Ts = 1400 °С. The scalability of our process was checked by the fabrication of a large (0.5 kg) and uniform cake of single-phase Ti2AlN. In experiments we used green samples with shielded lateral surface (bulk powder in silica tubes, plain layer in a closed molybdenum boat) and without shield (dense compacts). It has been shown that shielding of Ti–Al–TiN samples restricts the escape of Al vapor from a sintered mixture, thus providing more favorable conditions for the synthesis of single-phase Ti2AlN. Our process can be readily recommended for practical implementation.

Introduction. In most patients with colorectal cancer (CRC), the tumor develops against the background of metabolically healthy obesity or metabolic syndrome (more than 60 % of patients), the key pathogenetic moment of which is developing hyperinsulinemia. Metabolic changes are also characteristic of patients with colon polyps (CP), which are currently considered as the most significant precancerous diseases. It has been shown that fractions of small extracellular vesicles (EVs) of adipocyte origin are specifically enriched in extracellular matrix proteins, including matrix metalloproteinases (MMPs), chaperones, and some metabolic enzymes involved in the synthesis of lipids and carbohydrates. This was the reason for choosing exosomal markers in our study. Comparison of protein expression on CD9- and FABP-4 positive vesicles will be useful to explain some clinical issues, such as the effectiveness of thermoradiotherapy or radiotherapy in obese CRC patients; for a more substantiated search for vesicular prognostic markers in obese cancer patients. However, taking into account the lack of data in the literature on the level of MMPs and HSPs expression in the composition of the total pool of EVs and in the composition of FABP4-positive EVs in patients with PTC and CRC patients, the aim of the work was formulated.Aim. Study of the level of MMPs and heat shock proteins (HSPs) on CD9- and FABP4-positive EVs in patients with CP and CRC in relation to metabolic status.Materials and methods. The study included 12 patients with CRC (T2-4N0-2M0; mean age 59.6 ± 1.6 years) who were treated at the Department of Abdominal Oncology of the Cancer Research Institute of the Tomsk National Research Medical Center from 2019 to 2021. The comparison group included 10 patients with CP. The level of proteins on the surface of CD9- and FABP4-positive EVs was studied using flow cytometry.Results. MMP9-positive EVs were detected more often in CRC patients than in CP patients, however, MMP9+MMP2+TIMP-positive EVs were significantly more frequently detected in CP patients. Among the studied heat shock proteins, HSP60 was most often expressed on the surface of EVs, and HSP60-positive EVs were detected on the surface of CD9-positive exosomes in patients with PTC much more often than in CRC. In patients with CRC, compared with patients with СP, among FABP4-positive EVs, the proportion of triple-positive EVs and EVs with the MMP9+MMP2-TIMP1+ phenotype significantly increases, which in general may indicate overexpression of MMP9 and TIMP1 by adipocytes or marcrophages of adipose tissue in patients with CRC. Correlation analysis revealed multiple correlations of individual phenotypes of CD9-positive EVs in patients with CRC with body mass index and serum high density lipoprotein cholesterol levels, while the phenotypes of FABP4-positive EVs were associated mainly with triglyceride levels.Conclusions. The phenotypes of CD9-positive and FABP4-positive circulating EVs are promising as predictors for clarifying cancer risk in patients with colon polyps, as well as in terms of explaining the effectiveness of the treatment of CRC patients with obesity or metabolic syndrome.

Leukodystrophies are a group of hereditary progressive diseases of the central nervous system characterized by selective lesions in white matter with specific involvement of glial cells. There are hypomyelinating (absence of myelin deposition), demyelinating (loss of previously deposited myelin), dysmyelinating (deposition of structurally or biochemically abnormal myelin), and myelinolytic leukodystrophies (myelin vacuolization). Hypomyelinating leukodystrophies (HL), like most leukodystrophies, debut in childhood or adolescence and are characterized by a progressive course of the disease. HL occurs as a result of impaired synthesis of proteins responsible for the development, structure, and integrity of the myelin sheath, involved in the processes of transcription and translation. In the latter group, the main role is assigned to HL associated with biallelic mutations in the genes of the RNA polymerase III transcription complex, POLR3: POLR3A, POLR3B, POLR1C, and POLR3K. The diagnosis can be confirmed by magnetic resonance imaging of the brain. POLR3A-associated HL is manifested by hypomyelination, hypodontia, and hypogonadotropic hypogonadism. The magnetic resonance features of POLR3-associated HL include diffuse hypomyelination with relative preservation of the dentate nuclei, anterolateral nuclei of the thalamus, globus pallidus, pyramidal tracts at the level of the posterior part of the internal capsules, and the corona radiata. In some cases, thinning of the corpus callosum and atrophy of the cerebellum were also noted. The article presents a clinical case of a patient with POL3A-associated HL with spinal cord injury with the debut in early childhood.

The few foreign papers of the last decade have shown the relationship of various pathogenic variants of the ELAC2 gene to heterogeneous phenotypic manifestations, for which the unfavorable prognosis is common, caused by severe cardiomyopathy in the first year of life. The article presents the first clinical observation of a rare variant of the hypertrophic phenotype cardiomyopathy with a fatal outcome in the first year of life, and variants c.887T>C, p.L296P and c.1979A>T, p.K660I of the ELAC2 gene in Russia.The purpose of the work is to present clinical observation of a child with an early manifestation of a hypertrophic phenotype of cardiomyopathy caused by pathogenic variants of the ELAC2 gene.

One of the most important tasks of veterinary practice is to find and develop an effective and environmentally friendly method of disinfecting livestock room air that can be used in the presence of animals and service personnel. Currently, low-pressure discharge lamps are used for indoor air sanitation as a source of ultraviolet (UV) radiation. However, these devices can pose serious environmental pollution risks. Therefore, the main objective of this work was to investigate the bactericidal effectiveness of pulsed broadband optical radiation on the microbial contamination of the house air of livestock and concerning sanitary positive microorganisms. In the article, the authors presented a description of the technical characteristics of the Zarya-1 device based on the use of pulsed high-intensity optical radiation of a continuous spectrum. This spectrum is generated by powerful high-temperature (10000 – 40000 K) plasma sources, developed by SRIP (State Ryazan Instrument Plant) JSC. The bactericidal effect of broadband radiation on the microflora of the air in the livestock building was investigated. The experiment was carried out in the vivarium. Open Petri dishes with dense nutrient media were placed at three points for the deposition of dust particles, microorganisms, and aerosol droplets by gravity. The results obtained were recorded after 24 h. In their study, the authors revealed a reduction in the total microbial count of air in all five variants after exposure to irradiation for durations of 14, 16, 17, 18, and 19 min. Therefore, at the 14 min duration of irradiation, the effectiveness of the sanitary parameters reached 97.12 % and at the 19 min duration 99.78 %.

PRKAG2 syndrome is a rare genetic disease that isinherited in an autosomal dominant fashion and is caused by mutationsin the PRKAG2 gene. Clinical symptoms include early onset, ventricular preexcitation, cardiac hypertrophy, and progressive atrioventricular block. The PRKAG2 syndrome is characterized by genetic heterogeneity, which makes early detection difficult; genophenotypic correlations have been documented. In this article, we provide an overview of the literature data and experience from the cardiology department of the National Medical Research Center for Children’s Health of the Russian Ministry of Health in the diagnosis and management of patients with PRKAG2 syndrome, and present the clinical and genetic characteristics of the p.R302Q and p.H383R variants of the PRKAG2 gene.

Structurally modified virus particles can be obtained from the rod-shaped or filamentous virions of plant viruses and bacteriophages by thermal or chemical treatment. They have recently attracted attention of the researchers as promising biogenic platforms for the development of new biotechnologies. This review presents data on preparation, structure, and properties of the structurally modified virus particles. In addition, their biosafety for animals is considered, as well as the areas of application of such particles in biomedicine. A separate section is devoted to one of the most relevant and promising areas for the use of structurally modified plant viruses - design of vaccine candidates based on them.

The textbook examines theoretical and methodological issues of public health research, provides a comprehensive assessment of public health in the region based on relevant quantitative and qualitative parameters, identifies factors that affect health, and also considers the functioning of the health system. Meets the requirements of the federal state educational standards of higher education of the latest generation. For students in the master's degree in the field of training 38.04.01 "Economics" (focus: regional economy and territorial development, firm economics), as well as for teachers of higher educational institutions, researchers, students, postgraduates, specialists of health authorities and anyone interested in this topic.

This is the poster from the team working with the Magister Dixit-dataset for the KU Leuven Bibliotech Hackathon (2023). The poster gives a brief overview of what we did - i.e. analyzing the dated colophons and compiling them into a dataset - and details our process.

Histological studies of the ontogenetic changes in Arctic marine fishes are often fragmented and incomplete. Here we present a comprehensive histological ontogenetic analysis of the daubed shanny (Leptoclinus maculatus) from the Arctic, characterizing its development as it undergoes a series of changes in the organ and tissue organization, especially during the postlarvae transition from the pelagic to benthic lifestyle. The thyroid, heart, digestive tract, liver, gonads, blood, and the lipid sac of the postlarvae at different developmental stages (L1–L5) were studied for the first time. We found that L. maculatus has structural characteristics of marine fish developing in cold, high-oxygen polar waters. We conclude that the presence of the lipid sac and the absence of distinguishable red blood cells in pelagic postlarvae are unique features of the daubed shanny most likely linked to its successful growth and development in the Arctic environment.

The paper presents the results of the computer simulation of the thermohydrodynamic (THD) processes in a shallow water body based on the open software package Delft3D. The object of modeling is closed Lake Chany - the largest natural water body in Western Siberia. To construct a computer THD-model of Lake Chany digital elevation model of its basin was refined and a database containing meteorological information from coastal area stations and hydrological data of the lake and its tributaries was prepared. Simulation calculations of THD processes for open-water period in 2018 are performed. The analysis of the results showed that the constructed 2DH computer model of Lake Chany allows to reproduce the observed features of its thermal regime for the ice-free period.

About 80-90% of patients with Noonan syndrome have changes in the cardiovascular system, 30% of which include cardiomyopathy, hypertrophic phenotype in particular. The treatment of cardiomyopathy patients with Noonan syndrome is carried out according to the clinical recommendations for the treatment of chronic heart failure (CHF) and cardiomyopathy. Surgical treatment of progressive nature of heart failure with left ventricular outflow tract obstruction and mitral regurgitation can be one of the possible methods. The review presents our experience with septal myectomy (SM) in children suffered from hypertrophic obstructive cardiomyopathy with Noonan syndrome. Objective. To assess the efficiency of septal myectomy in children suffered from hypertrophic obstructive cardiomyopathy with Noonan syndrome. Materials and methods. Clinical examination (family history, patient examination), lab tests (NT-proBNP level), echocardiography, electrocardiography, Holter monitoring, Chest X-rays and molecular genetic methods using mass parallel sequencing (NGS) and direct automatic Sanger sequencing. The indications for the SM were determined according to the clinical guidelines for the diagnostic and treatment of hypertrophic cardiomyopathy. Results. 7 patients out of 48 with Noonan syndrome underwent SM and 1 with Noonan syndrome with multiple lentigo (LEOPARD). Two of them required the removal of obstruction of the outflow tracts of both ventricles, followed by plastic removal of the right ventricle and pulmonary artery valve. Related surgical interventions included aortic (n = 1) and mitral valves (n = 2), permanent pacemaker (n = 1) in the early postoperative period. After a year, all children recorded a decline of NT-proBNP from the average of 16,198 to 3,865 pg/ml, a significant improvement in health, disappearance of shortness of breath, increased physical activity tolerance, improved physical (weight, growth) and speech development. When assessing the dynamics of the Echo parameters 1 year after the SM, normalization of the size of both atria in 4 cases, reduction of severity of isolated dilation of the left atrium in 2 cases was noted. No cases of repeated obstruction have been reported. Conclusion. Hypertrophic cardiomyopathy (HCM) can be in structure of hereditary syndromes such as Noonan syndrome. Septal myectomy (SM) can now be used in the case of progressive nature of heart failure with left ventricular outflow tract obstruction in children with Noonan syndrome.

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a potentially curative treatment for patients with relapsed and refractory classic Hodgkin lymphoma (rrHL). However, the optimal conditioning regimen and GVHD prophylaxis for rrHL remain undetermined. The aim of this study was to investigate outcomes of allo-HSCT with a fludarabine plus bendamustine (FluBe) conditioning regimen and GVHD prophylaxis with posttransplantation cyclophosphamide (PTCY) in patients with rrHL.Allo-HSCT results in 58 adult patients with rrHL were analyzed retrospectively.Three-year overall survival and event-free survival were 81% (95% CI 65-91) and 55% (95% CI 38-72), respectively. The cumulative incidence of relapse (CIR) at 3 years was 33% (95% CI 13-51). The cumulative incidence of aGVHD grade II-IV and severe aGVHD grade III-IV was 36% (95% CI 22-48) and 22% (95% CI 9-33), respectively. The cumulative incidence of cGVHD was 32% (95% CI 17-45), including moderate or severe cGVHD in 17% (95% CI 4-28). Patients who developed aGVHD after allo-HSCT had significantly lower CIR (24% vs 49%, p = 0.004). The use of PBSC as a graft source also significantly reduced CIR (4% vs 61%, p = 0.002).FluBe-PTCY allo-HSCT facilitates favorable outcomes, low toxicity, and mortality in rrHL.

We present a new corpus-based resource and methodology for the annotation of Latin lexical semantics, consisting of 2,399 annotated passages of 40 lemmas from the Latin diachronic corpus LatinISE. We also describe how the annotation was designed, analyse annotators’ styles, and present the preliminary results of a study on the lexical semantics and diachronic change of the 40 lemmas. We complement this analysis with a case study on semantic vagueness. As the availability of digital corpora of ancient languages increases, and as computational research develops new methods for large-scale analysis of diachronic lexical semantics, building lexical semantic annotation resources can shed new light on large-scale patterns in the semantic development of lexical items over time. We share recommendations for designing the annotation task that will hopefully help similar research on other less-resourced or historical languages.

Rationale: During neoplastic transformation, epithelial cells become mobile, which is one of the main mechanisms of metastatic disease and recurrence. Cell motility is regulated by actin-binding proteins, which ensure the association/dissociation of actin filaments and their interaction with the cell membrane. Previously, we have shown the presence of actin-binding proteins in the serum from patients with squamous cell carcinoma of the head and neck (HNSCC); however, their association with the development of metastases and relapses in cancer patients has not been sufficiently studied. Aim: To evaluate the serum levels of actin-binding proteins fascin-1 and ezrin in patients with HNSCC depending on the disease recurrence and lymphatic metastasis. Materials and methods: Serum fascin-1 and ezrin levels before combination therapy were measured with ELISA assay in 30 HNSCC (T1-4N0-2M0) patients (mean age 56 7 years). Results: The median fascin-1 level was significantly higher in the patients with lymphatic metastases, compared to those without metastases: 0.64 (0.40; 5.89) vs 6.35 (1.72; 8.35) ng/mL, respectively (p 0.001). At 12 to 36 months after combination therapy, the disease relapsed in 12 (40%) patients. Ezrin levels were significantly higher in the relapsed patients, compared to those without a relapse within 3 years after combination therapy: 2.55 (2.35; 2.75) vs 1.93 (1.87; 2.5) ng/mL (p = 0.02). The ROC analysis showed an association between fascin-1 serum levels with metastatic disease (AUC = 0.71, 95% confidence interval 0.570.85) and an association between ezrin levels and the disease relapse (AUC = 0.76, 95% confidence interval 0.570.94). Conclusion: These indicators can be used for the development of minimally invasive early detection of metastases in lymphatic nodes and for the prognosis of HNSCC recurrence.

Introduction. Colorectal cancer (CRC) is one of the leading causes of death from cancer in the world and is also one of the most common forms of oncological pathology, which is characterized by a continuing steady increase in morbidity, a significant incidence of relapses, and early metastasis. Among the many signaling cascades that determine the features of the biological behavior of a tumor, great importance is attached to the AKT / mTOR signaling pathway. The study aimed to study the expression of AKT / mTOR signaling pathway components in tumors in patients with colorectal cancer, in connection with the clinical and morphological parameters of the disease and the objective response of the tumor to antitumor treatment. Materials and methods. The study included 26 patients with colorectal cancer aged 43 to 75 years (average age was 54 years). In the clinics of the Research Institute of Oncology of the Tomsk National Research Medical Center, patients received combined treatment, which included neoadjuvant chemotherapy according to the FOLFOX or XELOX scheme by radical surgery. The study material was normal and tumor tissue was obtained after surgical treatment. The mRNA level of the studied parameters was determined by real-time PCR. Results and discussion. A wave-like change in the expression of AKT, GSK-3β, the 70S 6 kinase, mTOR was found with an increase in the size of the primary tumor. The presence of lymphogenous metastases and the level of regional lymph node involvement (N1–2) were associated with changes in the mRNA level of the 70S 6 kinase, PTEN, GSK-3β, and mTOR. As a result of neoadjuvant chemotherapy, the level of 4EBP1 mRNA increased by 2.6 times compared with that before treatment. At the same time, the low treatment efficacy was associated with an increase in PDK1 expression and a decrease in c-RAF expression. Conclusion. Molecular features of the development of colorectal cancer associated with changes in the expression of the components of the AKT / mTOR signaling pathway, depending on the locoregional prevalence of the tumor and the effectiveness of antitumor therapy, have been identified, which affects the prognosis of the disease.

An outbreak of nodular gill disease (NGD) in farmed rainbow trout Oncorhynchus mykiss (Walbaum, 1792) was recorded in Ladoga Lake (Karelia, north-western Russia) in Spring 2020. The disease was characterised by typical clinical signs including asphyxiation, distended opercula, loss of activity and swimming upside down under the water surface. Maximum monthly mortality was 15.2%. The histological examination of the gills showed deformation and clubbing of lamellae, epithelial hypertrophy and hyperplasia, lamellar fusion and fusion of filaments. Granulomas were located within the epithelial layer and/or rose above its surface. Light microscopic in vivo observations of the mucus smears from the affected gills revealed numerous amoeboid protists demonstrating a flattened body when adhering to the substratum, and blunt, radiating pseudopodia when afloat. Based on these morphological characters, these amoebae could be assigned to the Discosea (Amoebozoa), and analyses of their small subunit rRNA gene sequences showed that they belonged to the genus Vannella Bovee, 1965. The results reported herein support the designation of a new species, V. mustalahtiana sp. nov. Despite having been isolated from the gills of a freshwater fish, the species belongs to a clade of Vannella comprising mostly species isolated from marine and brackish water habitats. These findings may be essential for the aetiology and treatment of the disease.

Studies into mitochondrial сomplexomes in various organisms provide an insight into the native organization of proteins and metabolic pathways in the organelles of the subject under study. “Complexome” is a relatively recent concept describing the proteome of protein complexes, supercomplexes, and oligomeric proteins. Complexome analysis is performed using current electrophoretic and mass spectrometric techniques, in particular, by two-dimensional electrophoresis (2D BN/SDS-PAGE) in combination with mass spectrometry (MS). Unlike 2D IEF/SDS-PAGE, this method enables analysis of not only hydrophilic proteins of the mitochondrial matrix, but also membrane proteins and their associations, thus expanding the possibilities of studying the organelle proteome. In the present work, the complexome of etiolated pea shoots was studied for the first time using 2D BN/SDS-PAGE followed by MALDI-TOF MS. To this end, 145 protein spots excised from the gel were analyzed; 110 polypeptides were identified and assigned to different functional groups. A densitometric analysis revealed that the major protein group comprised the enzymes of the mitochondrial energy system (1), accounting for an average of 43% of the total polypeptide content. The remaining 57% was primarily distributed among the following functional categories: pyruvate dehydrogenase complex and citric acid cycle (2); amino acid metabolism (3); nucleic acid processing (4); protein folding (5); antioxidant protection (6); carrier proteins (7); other proteins (8); proteins having unknown functions (9). The obtained data indicate the complex organization of the pea proteome. In addition to the enzymes of the OXPHOS system, the proteins of other functional categories are found to form supramolecular structures. It is suggested that the presence of proteins from other cellular compartments may indicate the interaction of mitochondria with the enzymes or structures of corresponding organelles. In general, the obtained data on the pea complexome represent a kind of a mitochondrial “passport” that reflects the native state of the proteome of organelles corresponding to their physiological status.

Aim. To analyze the first experience of administering polatu-zumab vedotin combined with bendamustine and rituximab (Pola-BR) in clinical practice at some specialized institutions in the Russian Federation. Materials & Methods. The prospective multi-center study enrolled 39 patients with relapsed/refractory aggressive В-cell non-Hodgkin’s lymphomas (B-NHLs): 31 (79 %) patients with diffuse large B-cell lymphoma, 7 (18 %) patients with primary mediastinal (thymic) large B-cell lymphoma, and 1 (3 %) patient with gray zone lymphoma. There were 20 men and 19 women aged 19-69 years (median 43 years). All the patients were treated with Pola-BR protocol: bendamustine 90 mg/m2 on Days 1 and 2, rituximab 375 mg/m2 on Day 1, and polatuzumab vedotin 1.8 mg/kg on Day 1 of each 21-day cycle. Full treatment with 6 cycles was completed by 19 patients. PET-CT was performed prior to therapy and after the 2nd, 4th, and 6th Pola-BR cycles. The tumor response was evaluated according to the Lugano 2014 criteria. The toxicity profile was assessed by means of reporting adverse events according to the NCI CTCAE, version 5.0. Results. Objective response to the therapy, according to the Lugano 2014 criteria, was identified in 24 (61.5 %) patients: 19 (48.7 %) of them showed the complete response, and 5 (12.8 %) of them showed the partial one. Stable disease as best response to the therapy was reported in 3 (7.7 %) patients, disease progression was observed in 12 (30.8 %) patients. By the time of data analysis, the median follow-up duration was 16.8 months (range 5.3-24.2 months). The 2-year overall survival (OS) was 44 % (95% confidence interval [95% CI] 24-62 %), the median OS was 20.8 months. The 2-year progression-free survival (PFS) was 27 % (95% CI 12-43 %), the median PFS was 7.3 months. Adverse events of grade 3/4 included anemia (n = 4; 10.3 %), neutropenia (n = 15; 38.5 %), thrombocytopenia (n = 3; 7.7 %), and febrile neutropenia (n = 2; 5.1 %). In 2 patients with history of hepatitis B, the virus reactivation was identified on Pola-BR therapy. No cases of peripheral neuropathy were observed. Conclusion. Results obtained in real-world clinical practice correspond to the previously published data and demonstrate that polatuzumab vedotin therapy (Pola-BR protocol) has a controllable toxicity profile and is, therefore, a promising chemotherapy method of relapsed/refractory aggressive B-NHL treatment.

This case report highlights the benefit or harm of breastfeeding in a patient with Kidney Failure with Replacement Therapy (KFRT) undergoing program hemodialysis. This is a unique clinical case, as pregnancy and successful delivery are rare in this group of females. With a favorable outcome, the possibility of breastfeeding is especially relevant for doctors and the mother. The patient was a 31-year-old female who was diagnosed in 2017 with end-stage renal disease associated with chronic glomerulonephritis. Against the background of hemodialysis, pregnancy, accompanied by polyhydramnios, anemia, and secondary arterial hypertension, occurred in 2021. At 37 weeks, a healthy, full-term baby girl was born, and breastfeeding was started. In this study, we conducted a detailed analysis of toxic substances and immunologically significant proteins using high-tech analysis methods. In addition, we studied different portions of milk before and after hemodialysis at different time intervals. After a wide range of experiments, our study did not reveal an optimal time interval for breastfeeding a baby. Despite the decrease in the level of the major uremic toxins 4 h after the hemodialysis procedure, their level remained high. In addition, the content of nutrients did not reach acceptable limits and the immune status was characterized as pro-inflammatory. In our opinion, breastfeeding is not advisable for this group of patients since the concentration of nutrients is low, and the content of toxic substances exceeds the permissible limits. In this clinical case, the patient decided to stop breastfeeding one month after delivery due to insufficient breast milk and the inability to express it in a certain period of time.

Clinical, radiological, and laboratory data of 62 patients with respiratory tuberculosis were studied with the purpose of comparative analysis of clinical efficacy of Glutoxime and Tubosan and evaluation of efficiency of the empirical approach in drug selection. Three groups of patients were formed: the 1st group - 20 patients who received Glutoxim along with anti-tuberculosis drugs. Group 2 - 23 patients (Tubosan), Group 3 – control, 19 patients (only anti-tuberculosis drugs). Empirical approach to the choice of pathogenetic drugs has a limited positive effect on the efficacy and tolerability of etiotropic therapy. In the conditions of forced polypragmasy, the prescription of drugs should be justified by modern highly informative criteria, not being limited only by clinical indications.

The article reveals the appearance and development of the educational aspects of the Russian-Chinese dialogue in the context of relations between Russia and China in recent years. The analysis is based on bilateral analytical documents from «Russia-China Dialogue: Model 2015» to «Russia-China Dialogue: Model 2020», which cover the educational aspects of cooperation. The analysis has shown that possessing the equal opportunities of the established Russian-Chinese humanitarian areas, Chinese and Russian experts note not only the positive aspects of the implementation of the program but also the problems that arise at the worldview level, at a time having justified the results of cooperation and its prospects. This is facilitated by the principle of determinism, historical and integrative approaches, and phenomenological and comparatives analyses.

Duchenne muscular dystrophy (DMD) is a hereditary progressive muscular dystrophy, mainly manifested in boys, is characterized by the onset at an early age, gradual symmetrical atrophy of the striated musculature of the limbs, trunk, as well as damage to the heart muscle. As a rule, girls and women inheriting a pathological mutation are classified only as its carriers and do not have clinical manifestations of the disease. Rare cases when women or girls show clinical manifestations of DMD may be due to chromosomal rearrangements involving the region of the short arm of the X chromosome (Xp21.2), deletions of this region, complete loss of the X chromosome (Shereshevsky-Turner syndrome), homogenous X chromosome dysomnia, compound heterozygous state for two pathogenic mutations in the DMD gene, nonequilibrium inactivation of the X chromosome. When female mutation carriers have DMD clinical symptoms, they usually manifest much milder than boys and young males. Descriptions of patients with the severe course and rapid progression of the disease, comparable in the rate of progression with boys, are rare. In this article, the authors share their experience of observing a girl patient who suffered from a severe form of DMD.

We previously exposed the role of actin-binding proteins (ABPs) in cancer development and progression. In this paper, we studied the relationship between circulating ABPs and the number of ABP-expressing leukocytes and circulating tumor cells (CTCs) in patients with highly aggressive laryngeal squamous cell carcinoma (LSCC). The levels of cofilin (CFL1), profilin (PFN1), ezrin (EZR), fascin (FSCN1), and adenylate cyclase-associated protein 1 (CAP1) were determined using enzyme immunoassay. The ABP expression by the cellular pools was analyzed by flow cytometry. The highest levels of FSCN1 and EZR were found in the blood serum of LSCC patients. There was a difference in ABP expression between the pools of leukocytes and CTCs. Leukocytes were mainly represented by CAP1+ and FSCN1+ pools, and CTCs contained CAP1+, FSCN1+, and EZR+ cells. The serum FSCN1 level correlated with the number of FSCN1-containing and CFL1-containing leukocytes. Thus, the level of circulating EZR is likely related to its expression in CTCs. The levels of CFL1 and PFN1 are likely to be supported by the expression of these proteins by leukocytes. Both CTCs and leukocytes can be a source of FSCN1 and CAP1 in blood serum. The results suggest that serum proteins can be produced by various cells, thus indicating both cancer development and the response of the immune system to this process.

Разработанный электронный ресур направлен на формирование у студентов 1 курса понимания о том, как организовано обучение в УГМУ

Duchenne muscular dystrophy (DMD) is a disease with an X-linked recessive type of inheritance, belonging to a group of disorders with primary muscle damage, caused by pathogenic variants in the DMD gene and associated with dysfunction of the dystrophin protein. Since DMD is manifested by the gradual development of progressive, mainly proximal muscle weakness, the differential diagnosis is primarily carried out in the group of diseases with muscle damage - myopathies. Among these diseases, the leading candidates for differential diagnosis are hereditary myopathies (limb-girdle muscular dystrophies, facioscapulohumeral dystrophy, congenital muscular dystrophies, glycogenoses - the most common juvenile form of glycogenosis type II (Pompe disease)) and, much less often, congenital myopathies and other conditions of neuromuscular diseases). When conducting a differential diagnosis in a child with suspected DMD, the age of the onset of the disease, early initial clinical manifestations and the development of symptoms as they grow, genealogical analysis, laboratory tests (the level of creatine kinase, aspartate aminotransferase, alanine aminotransferase in blood serum), instrumental (electromyography, magnetic resonance imaging of the brain and muscles) and molecular genetics (polymerase chain reaction, multiplex ligation-dependent probe amplification, next-generation sequencing, Sanger sequencing, etc.) of studies, and in some cases, muscle biopsy data. Knowledge of the nuances of the differential diagnosis allows establishing a genetic diagnosis of DMD as early as possible, which is extremely important for the formation of the prognosis of the disease and the implementation of all available treatment methods, including pathogenetic therapy, and is also necessary for medical and genetic counselling of families with DMD patients.