Background. Colorectal cancer is ranked third in terms of incidence and second in terms of mortality around the world. Molecular markers of chemoresistance allow to determine the prognosis of the disease and sensitivity of the tumor to drugs.

Aim. To assess the predictive value of expression of regulators of tumor-associated inflammation TGFb1 and CXCL8 in the tumor tissue in colorectal cancer.

Materials and methods. Patients were divided into 3 groups: group I included patients without relapse of the disease, group II encompassed patients with relapse of the disease (within 6–16 months after the end of chemotherapy), group III included patients with disease progression. Expression of TGFb1 and CXCL8 in the tumor tissue before treatment in patients with stage II–III colorectal cancer (n = 77) was determined using quantitative realtime polymerase chain reaction (PCR) on the Bio-Rad CFX-96 Touch Real-Time PCR Detection System (USA). Statistical data processing was performed using Statistica 13.0 software (StatSoft, USA).

Results. We found that in samples of poorly differentiated colorectal cancer, the level of TGFb and CXCL8 mRNA was significantly higher than in moderately and well differentiated tumors. We did not reveal any relationship of the level of TGFb1 and CXCL8 transcripts in tumor samples of patients with stage II–III colorectal cancer with age and the presence of mutations in the EGFR (Epidermal Growth Factor Receptor) signaling pathway (RAS, BRAF). We found a strong positive correlation between the levels of TGFb1 and CXCL8 transcripts for the entire sample of patients with colorectal cancer. We have found that the expression of TGFb1 and CXCL8 genes was significantly higher in the tumor tissue of patients with disease progression.

Conclusion. Overexpression of TGFb1 and CXCL8, which are involved in the mechanism of tumor-associated inflammation, can be considered as a negative prognostic factor for the progression-free interval when using the FOLFOX / XELOX regimen for the treatment of colorectal cancer.

Aim. To assess the effect of an indolinone derivative (2-[2-[(5RS)-5-(hydroxymethyl)-3-methyl-1,3-oxazolidine-2yliden]-2-cyanoethylidene]-1H-indole-3(2H)-one (codename – GRS) on right ventricular contractility, endothelial vasodilator function, and histologic changes in the lungs and heart in a rat model of monocrotaline-induced pulmonary hypertension.

Materials and methods. Pulmonary arterial hypertension (PAH) was induced in Wistar rats by a single subcutaneous administration of monocrotaline at a dose of 60 mg / kg. Starting from day 15 after PAH induction, the rats received either GRS at a dose of 10 mg / kg or riociguat at a dose of 1 mg / kg orally once a day. Blood pressure in the right ventricle, right ventricular weight, endothelial vasodilator function, and the histologic structure of the lungs and heart were studied after the last administration of test substances.

Results. Twenty-eight days after monocrotaline administration, the rats developed PAH, as shown by the increase in the maximal blood pressure in the right ventricle and the right ventricular weight / total heart weight ratio. GRS after multiple administration reduced the maximal blood pressure in the right ventricle, had no significant effect on its contractility, improved endothelial vasodilator function, and normalized blood pressure. Riociguat had a hypotensive effect and did not alleviate endothelial dysfunction in experimental PAH.

Conclusion. The indolinone derivative GRS and riociguat, both soluble guanylate cyclase stimulators, lowered blood pressure in the right ventricle. GRS also alleviated endothelial dysfunction in animals with experimental PAH.

Aim. To study the anti-allergic effects of ruzam, an extract from the culture of a thermophilic Staphylococcus aureus strain, in an in vivo model of asthma and its influence on degranulation of mast cells and basophils in vitro.

Materials and methods. Allergic asthma in guinea pigs was reproduced by two intraperitoneal injections of ovalbumin followed by a series of inhalations of this antigen for 1.5 months. Ruzam (6 μg / kg) or a reference drug (sodium cromoglycate, 3 mg / kg) was administered daily via a nebulizer during the last 6 days of immunization. One day after completion of inhalations with ovalbumin and compared drugs, changes in the airways were assessed using cytological, morphometric, and histologic methods. Rabbit blood basophils and rat peritoneal mast cells were used to determine the effect of ruzam on IgE-independent degranulation induced by the compound 48 / 80 in vitro. The effect of ruzam was compared with that of hydrocortisone hemisuccinate. Basophils from the blood of ovalbumin-sensitized guinea pigs were used to evaluate the effect of the drug on IgE-dependent degranulation induced by ovalbumin. Granules of mast cells and basophils were detected by alcian blue staining to calculate the degranulation index.

Results. In the asthma model, ruzam reduced the degree of airway obstruction by increasing the bronchoalveolar lavage volume returned and suppressed neutrophilic and eosinophilic inflammation, while mobilizing other effector cells of the anti-pathogen immunity (lymphocytes and macrophages). Ruzam has proven to have a stronger anti-allergic effect than sodium cromoglycate by several parameters. At concentrations of 8.4–840 μg / ml, ruzam inhibited degranulation of mast cells and basophils, induced by the compound 48 / 80, equally to hydrocortisone hemisuccinate (10–3 M). At concentrations of 280 and 420 μg / ml, ruzam dose-dependently inhibited ovalbumin-induced degranulation of basophils in sensitized guinea pigs.

Conclusion. The anti-allergic effect of ruzam was confirmed in test systems in vivo and in vitro. We speculate here that the TLR2 signaling pathway may be involved in biological and pharmacological effects of this drug.

Aim. To evaluate the clinical and prognostic value of the inferior vena cava (IVC) diameter, the sum of B-lines according to lung ultrasound (LUS), and the NT-proBNP level in patients with acute decompensated heart failure (ADHF) and obesity.

Materials and methods. A single-center, prospective study included 162 patients with ADHF (66% men, age 68 ± 12 years, left ventricular ejection fraction (LVEF) 44 (35; 54)%, median level of NT-proBNP 4,246 (1,741; 6,837) pg / ml). 27.8% of patients were overweight, 55% of patients had obesity. Upon admission, all patients underwent a standard clinical and laboratory examination, including lung ultrasound with the calculation of the sum of B-lines, IVC ultrasound, and determination of the NT-proBNP level.

Results. Obese patients had a smaller sum of B-lines according to lung ultrasound than overweight patients and those with normal weight [33 (21–51); 38 (27–54), and 42 (30–58), respectively; p = 0.002] and a lower level of

NT-proBNP [3,404 (1,630; 5,516); 4,458 (2,697; 5,969); 5,085 (2,871; 7,351) pg / ml, respectively, p = 0.013]. The

IVC diameter did not differ significantly depending on body mass index (BMI): with obesity – 2.3 (1.9–2.8) cm, with overweightness – 2.3 (1.9–2.8) cm, and with normal weight – 2.2 (1.8–2.4) mm, p = 0.324.

According to the multivariate Cox regression analysis, the sum of B-lines > 7 at discharge (hazard ratio (HR) 8.90, 95% confidence interval (CI) 2.03–38.30, p = 0.003) and IVC > 2.4 cm at admission (HR 5.42, 95% CI 1.04–28.13, p = 0.045) were independently associated with a higher risk of 12-month mortality from cardiovascular disease.

Conclusion. Therefore, lung ultrasound with B-line quantification and assessment of the IVC diameter may be useful in obese patients with ADHF to stratify the risk of 12-month mortality from cardiovascular disease.

Aim. To study the prognostic value of myocardial blood flow (MBF) and myocardial flow reserve (MFR) parameters in patients with heart failure with preserved ejection fraction (HFpEF) and non-obstructive coronary artery disease (CAD) in risk stratification of HFpEF progression during a 12-month follow-up.

Materials and methods. The study included 58 patients with non-obstructive CAD and HFpEF (LVEF 62 [58; 66]%). Dynamic CZT-SRECT was used to evaluate MFR and MBF at rest (rest-MBF) and stress (stress-MBF). NT-proBNP levels were determined by the enzyme immunoassay. Diastolic dysfunction parameters were measured using 2D transthoracic echocardiography. Left ventricular systolic global longitudinal strain (GLS) was assessed using 2D speckle tracking.

Results. After a 12-month follow-up, the patients were retrospectively divided into 2 groups: group 1 (n = 11) included patients with an unfavorable course of HFpEF, group 2 (n = 47) encompassed patients with a favorable course of the disease. In group 1, the level of NT-proBNP was 3.8 times higher than in group 2 (284.5 [183.42; 716.73] and 1,071.4 [272.4; 2,168.1] pg / ml, respectively). MFR values in group 1 were lower by 45.4%

(p < 0.001) than in group 2 (1.19 [0.86; 1.55] vs. 2.18 [1.7; 2.55], respectively). In group 1, rest-MBF levels were higher by 23.6% (p = 0.046) and stress-MBF was lower by 28.2% (p = 0.046) than in group 2. The multivariate regression analysis revealed that NT-proBNP levels (odds ratio (OR) 3.23; p = 0.008), GLS (OR 2.27; p = 0.012), and MFR (OR 8.09; p < 0.001) were independent predictors of adverse outcomes in HFpEF. Based on the ROC analysis, MFR levels ≤ 1.62 (AUC = 0.827; p < 0.001), GLS ≤–18 (AUC = 0.756; p = 0.002), and NT-proBNP

≥ 760.5 pg / ml (AUC = 0.708; p = 0.040) may be considered as markers of adverse outcomes. However, the combined determination of NT-proBNP and MFR had a greater significance (AUC 0.935; p < 0.001) in risk stratification compared with the monomarker model, while the addition of GLS did not increase the significance of the analysis.

Conclusion. Levels of NT-proBNP, GLS, and MFR may be used as non-invasive markers of an adverse course of HFpEF in patients with non-obstructive CAD, while the combined determination of NT-proBNP and MBF increases the prognostic value of the analysis.

Background. According to the latest epidemiological data, heart failure (HF) is diagnosed in 10% of adult population over 70 years old. However, currently this diagnosis is being increasingly made in young and middleaged people. The pathogenesis of HF may be based on a decrease in respiration in cardiomyocytes with age, which affects the function of energy-dependent processes in cells.

Aim. To study respiration in cardiomyocytes and microviscosity of their membranes in rats aged 2 and 15 months with heart failure.

Materials and methods. The study was carried out on male Wistar rats. The animals were divided into 4 groups: 2 groups of intact rats aged 2 and 15 months (n = 12) and 2 groups of animals of similar ages (n = 10) with a model of HF. In the latter, HF formed by day 28 after a double subcutaneous injection of isoproterenol hydrochloride at a dose of 170 mg / kg with an interval of 24 hours. Isolated cardiomyocytes were obtained from enzyme-washed rat hearts. Cell respiration was studied in a thermostated chamber in an incubation medium supplemented with phosphorylation (ADP) and oxidation (succinate) substrates. The respiratory control (RC) ratio was calculated by dividing V3 respiration state to V4. Membrane microviscosity characteristics were assessed by the eximerization coefficient of pyrene fluorescence in the areas of protein – lipid and lipid – lipid interactions.

Results. RC in cardiomyocyte membranes of intact animals did not change with age. In 2-month-old rats with HF, respiratory control ratio (RCR) did not change compared with the intact age-matched controls. In 15-month-old rats with HF, there was a significant decrease in RC of cardiomyocytes (CM) compared with the intact animals of this age and 2-month-old rats with HF. An age-dependent decrease in the microviscosity of CM membranes in the areas of lipid – lipid interactions and no significant changes in the parameter at the sites of protein – lipid interactions were noted. In 2-month-old animals with HF, the microviscosity of CM membranes in the areas of protein – lipid interactions significantly decreased, and in 15-month-old rats it increased, compared with the intact controls. When carrying out an intergroup comparison, an age-dependent increase in the microviscosity of CM membranes in the areas of protein – lipid interactions and no differences in the parameter in the areas of lipid – lipid interactions were revealed.

Conclusion. In the intact rats, the absence of significant changes in respiration with age was revealed. In the 15-month-old animals with HF, respiration in CM was significantly lower than in the intact controls and 2-monthold animals with HF. These changes may be due to the differences in the membrane microviscosity characteristics in different periods of ontogenesis.

Objective: identify differences or comparability of constitutional-morphological characteristics and indicators of the fatty constitution between patients with schizophrenia and people with MetS and without mental disorders.

Materials and methods. We examined 63 patients with schizophrenia and MetS (25 women, 38 men), aged 30 [33;52], and 50 mentally healthy individuals with MetS (28 women, 22 men) aged 57 [49; 60]. The main criterion for inclusion in the study was the presence of a verified MetS according to the criteria of the International Diabetes Federation. Anthropometric examination was performed according to the method of V.V. Bunak (1941) with the underlying calculation of integral indices. The determination of the fat component included: measuring waist circumference; non-invasive bioimpedancemetry – body weight, BMI, total and visceral fat content; determination of the total fat fold (electronic caliper). In the blood serum, the concentration of glucose, total cholesterol, HDL, TG was determined using standard commercial kits, the calculation of LDL and the Atherogenic Index.

Results. Differences in the prevalence of the constitutional-morphological type and the type of somatic sexual differentiation were not established in the groups. The level of visceral fat and BMI were higher in mentally healthy individuals with MetS than in schizophrenic patients with MetS (p = 0.005 and p = 0.0001, respectively). Patients with schizophrenia and MetS had low serum glucose levels compared with individuals without mental disorders (p = 0.0001). An increase in the level of TG and the Atherogenic Index was found in patients with schizophrenia with MetS (p = 0.026 and p = 0.03, respectively), and the level of HDL was reduced (p = 0.022).

Conclusion. The constitutional and morphological basis of MetS in patients with schizophrenia and persons without mental disorders is the same, however, changes in the fat constitution were determined for mentally healthy individuals. Changes in the lipid profile and glucose concentration may be associated with the presence of MetS-specific risk factors for patients with schizophrenia.

Аim. To study the possibility of using a radiopharmaceutical based on aluminum oxide labeled with ^99mТс ([^99mТс]-Al₂O₃) for the diagnosis of sentinel lymph nodes (SLN) in tumors of the larynx and laryngopharynx in comparison with a phytate colloid ([^99mTc]-phytate colloid).

Materials and methods. The study included patients with cancer of the larynx and laryngopharynx (T_2–4N₀M₀) (n = 54). In the prospective group (n = 30), [^99mТс]-Al₂O₃ was used as a radiopharmaceutical, in the retrospective group (n = 24), [^99mТс]-phytate colloid was used. All radiopharmaceuticals were introduced endoscopically into the submucosal space along the periphery of the tumor. After 18 hours, single-photon emission computed tomography (SPECT) and intraoperative SLN detection were performed.

Results. In the retrospective group, SLNs were detected in 20 out of 24 patients. A total of 32 lymph nodes were identified in the retrospective group. The median number of detected lymph nodes in one patient was 1.3 [0–3], the intensity of the radiopharmaceutical uptake on scintigrams was 2.2 [0.7–8.1], intraoperatively – 4 [1.6–9.0]. In the prospective group, [^99mTc]-Al₂O₃ uptake in the lymph nodes of the neck was determined in 27 patients (90%); in
3 patients, SLNs were not visualized. A total of 57 lymph nodes were identified (in 27 patients). The median number of visualized SLNs was 1.5 [0–5], the intensity of [^99mТс]-Al₂O₃ uptake according to SPECT and intraoperative detection was 4.8 [0.7–19.4] and 6 [1.1–22.0], respectively.

Conclusion. The most significant advantage of using [^99mТс]-Al₂O₃ as a radiopharmaceutical is its high uptake in SLNs, which leads to an increase in the sensitivity of the method as a whole up to 90 versus 83% when using [^99mTc]-phytate colloid.

Aim. To study pathohistological changes in the myocardium of rats with chronic alcohol intoxication (CAI) after treatment with a new glutamic acid derivative glufimet (compound RSPU-238) and a new gamma-aminobutyric acid (GABA) derivative (compound RSPU-260).

Materials and methods. Experiments were performed on female Wistar rats aged 10 months. The rats were divided into the following groups: group 1 – intact females; group 2 – a control group which included animals after CAI simulated by replacing drinking water with 10% ethanol solution for 24 weeks; groups 3 and 4 – experimental groups, in which females were intraperitoneally administered with glufimet at a dose of 28.7 mg / kg and RSPU260 at a dose of 25 mg / kg once a day for 14 days after cessation of alcohol solution consumption; group 5 – a group of animals receiving a reference listed drug mildronate at a dose of 50 mg / kg according to a regimen similar to that of the studied compounds. Changes in microstructural and morphometric parameters of the left ventricular myocardium were assessed using light microscopy.

Results. In animals after CAI, the cardiomyocyte volume fraction decreased, while the interstitial and vascular volume fractions increased. Degeneration of cardiomyocytes, such as their wave-like deformation, loss of transverse striation, foci of plasmolysis, and fragmentation of muscle fibers were revealed. In rats treated with glufimet, the structural changes in cardiomyocytes were minimal. Lower vascular plethora was observed; blood vessels were characterized by single stasis and sludge. The cardiomyocyte volume fraction was 9.7% greater than in control animals, while the interstitial and vascular volume fractions were 66.0 and 70.0% smaller, respectively. The animals treated with the RSPU-260 compound had no significant degenerative changes in cardiomyocytes and small vessels similar to the experimental animals injected with glufimet. Mildronate had a less pronounced cardioprotective effect.

Conclusion. Administration of new GABA and glutamic acid derivatives to animals with simulated chronic alcohol intoxication leads to improvement of the microstructure in cardiomyocytes compared with control rats. This indicates pronounced cardioprotective effects of the studied neuroactive amino acid derivatives.

Growing incidence of diabetes mellitus (DM), given significant socioeconomic consequences that low-trauma fractures entail, determines a need to improve diagnostic standards and minimize the risk of medical errors, which will reduce costs and contribute to better treatment outcomes in this category of patients.

Aim. To assess diagnostic capabilities of the method based on the use of an artificial neural network (ANN) for predicting changes in reparative osteogenesis in diabetes mellitus.

Materials and methods. A single-center, one-stage, cross-sectional study included 235 patients with type 1 and type 2 diabetes mellitus and 82 persons of the control group (the total of 317 patients). Further, the obtained data were processed using the MATLAB software to develop an ANN with a training (80%) and test (20%) set. The ANN model was trained by optimizing the relationship between a set of input data (a number of clinical and laboratory parameters: gender, age, body mass index, duration of diabetes mellitus, etc.) and a set of corresponding output data (variables reflecting the state of bone metabolism: bone mineral density, markers of bone remodeling).

Results. The ANN-based algorithm predicted estimated values of bone metabolism parameters in the examined individuals by generating output data using deep learning. Machine learning was repeated until the error was minimized for all variables. The accuracy of the validation test to predict changes in bone metabolism based on patient data was 92.86%.

Conclusion. The developed ANN-based method made it possible to design an auxiliary tool for stratification of patients with changes in bone metabolism in diabetes mellitus, which will help reduce healthcare costs, speed up the diagnosis due to fast data processing, and customize treatment for this category of patients.

Aim. To study the association between the functional potency and degree of maturity of B lymphocytes and PD-L1 expression in breast cancer patients.

Materials and methods. The study included 37 patients with the morphologically verified diagnosis of invasive breast cancer of no special type (IBC NST). The PD-L1 status was determined immunohistochemically using the Ventana SP142 assay (Roche, USA). Using the multiplex flow cytometry-based assay and high-throughput sequencing of the tumor microenvironment, subpopulations of B lymphocytes and their CD27 and PD1 expression profiles were determined, taking into account the PD-L1 status.

Results. In the tumor microenvironment, regardless of the PD-L1 status, expression signatures of five lymphocyte subpopulations were determined. However, in PD-L1-positive patients, the levels of B lymphocytes and immunoglobulin class-switched B lymphocytes were higher compared with PD-L1-negative patients. Evaluation of the number of different B lymphocyte subpopulations by flow cytometry showed that PD-1-positive B lymphocytes predominated in the tumor microenvironment in PD-L1-positive patients, regardless of the degree of lymphocyte maturity.

Conclusion. The results of the study showed predominance of mature committed B lymphocytes and memory B lymphocytes capable of synthesizing immunoglobulins of different classes and Th2 cytokines involved in type 2 immune response in PD-L-positive tumor microenvironment. It suggests that immunotherapy with PD-L1 inhibitors is highly likely to activate cells with protumor potential and can ultimately contribute to breast cancer progression.

Aim. To analyze the structural, magnetic, and cytotoxic features of magnetite nanoparticles (MNPs) prepared by the exploding wire method and stored in a dark place at ambient temperature (65 ± 15% humidity, air pressure 760

± 20 mm Hg., temperature 22 ± 4 °C) for 10 years.

Materials and methods. The properties of MNPs were analyzed by X-ray diffraction (XRD), transmission electron microscopy (TEM) and selected area electron diffraction (SAED), and vibrating-sample magnetometer (VSM). Viability of human blood mononuclear leukocytes was determined using 0.4% trypan blue staining after 24-hour culture with the nanopowder.

Results. The calculated size of the particles remained almost unchanged after 10 years of storage. The XRD and SAED patterns showed that crystallinity was preserved for 10 years. The diameter of the crystalline component of MNPs (D_XRD) was close to the particle size determined by TEM. It confirms high crystallinity of the tested nanoparticles. Saturation magnetization (M_S) of the MNP powder after 10 years of storage was unexpectedly higher than that of the as-prepared MNP powder. Reduced remanent magnetization (M_R / M_S) was equal for both samples within the margin of error. No cytotoxic effect of MNPs in vitro was detected in the long-term study.

Conclusion. No dramatic changes in the structural, magnetic, and cytotoxic features of MNPs were noted after 10 years of storage. It indicated 10-year stability of MNP powder that may be a useful feature for environment safety and biomedical applications.

Microbiota (an assembly of bacteria, protists / archaea, fungi, and viruses inhabiting a human body) is currently of great interest for science. It is determined by an association between changes in microbiota composition and malignant transformation in different organs. Lungs have long been considered sterile or free from bacteria; however, due to development of next-generation sequencing, this statement has been reconsidered. The metagenomic approach allowed to identify microorganisms at molecular level both in healthy lung tissues and in malignant ones.

The next stage of research is investigation of the effects of microbiota on homeostasis and immune stability in the lungs. The analysis of lung microbiota based on 16S rRNA gene sequencing revealed that microbiota of healthy lungs is mainly presented by bacteria of the phyla Bacteroidetes, Firmicutes, Proteobacteria, and Fusobacteria. In lung cancer, an increase in the number of bacteria of some certain genera and a decrease in microbiota diversity on the whole are noted. Dysbiosis facilitates reproduction of pathogens and development of lung diseases. It was detected that under normal conditions, microbiota maintains resistance of the lungs to bacterial colonization and plays a crucial role in providing a balanced immune response in this organ.

Important changes regarding the understanding of the pathogenesis of chronic heart failure (CHF) marked the beginning of the millennium, and its first decade was called the decade of diastology. Even though numerous studies convincingly proved that deterioration of the left ventricular (LV) filling pressure often precedes impairment of its systolic function and a number of factors affect (especially at the onset) mainly the diastolic function without changing the conditions of blood ejection, modern classifications and approaches to CHF treatment are primarily based on the results of LV ejection fraction (EF) assessment.

In recent years, diastolic heart failure (DHF) has been often overlooked and replaced by the ambiguous term “CHF with preserved EF”. However, sometimes authors use the term DHF extensively, since CHF based on myocardial insufficiency develops only via two mechanisms (systolic and / or diastolic dysfunction), and excluding one of the mechanisms allows to identify the underlying one. The term DHF can be used in clinical practice and cannot be replaced by the diagnosis of CHF with preserved EF. CHF with preserved EF is a broader concept which includes a full spectrum of cardiovascular diseases, complicated by the development of CHF without depression of the global LV contractility and requiring differentiated approaches to therapy. In addition, the results of repeated studies on LVEF in many patients may require reclassification of this CHF phenotype, which is established following the analysis of the baseline value of global LV contractility. We join M.R. Zile in the appeal to stop discriminating against the term “DHF” and present the boundaries of its correct application.

Diagnosing bacterial infection in patients with novel coronavirus infection (COVID-19) is not an easy task. Available data suggest that bacterial infection in patients with COVID-19 is rare and occurs in less than 10% of cases. At the same time, data of individual studies and systematic reviews indicate that more than 70% of patients with COVID-19 receive mainly empirical antimicrobial therapy with broad-spectrum antibiotics often before the diagnosis of COVID-19 has been verified. Therefore, this widespread empirical use of antibiotics is not supported by data on the need for their use.

The article discusses the literature data on the significance of commonly accepted methods for diagnosing bacterial infection, with an emphasis on laboratory presence / absence tests. In everyday practice, the likelihood of bacterial coinfection in patients with COVID-19 is assessed by clinical presentation of the disease and the results of standard laboratory tests and imaging methods. However, when viral respiratory infection develops, this approach does not always allow to diagnose bacterial coinfection with sufficient significance. This issue may be handled by available modern test systems, the use of a combination of signs or additional laboratory criteria (for example, procalcitonin), and the analysis of the overall clinical presentation by the doctor using knowledge about patient risk groups.

Aim. To analyze modern methods for the diagnosis of trematodiasis in experimental and epidemiological studies.

Trematodiasis is a group of common parasitic diseases that are a socially sensitive health problem worldwide. According to World Health Organization, more than 250 million people are affected by trematode infections globally. The most common types of human trematode infections are diseases caused by Schistosoma, Fasciola, Clonorchis, and Opisthorchis pathogens. Diagnosis of trematodiasis is often multistage and includes identification of disease symptoms, analysis of medical history, and use of various laboratory tests. Clinical presentation of parasitic infections often varies, making a definitive diagnosis difficult. Various tools are used to diagnose trematode infections: epidemiological criteria, laboratory tests (complete blood count and blood biochemistry, serological methods), instrumental methods (abdominal X-ray and ultrasound), and parasitological techniques, which often have insufficient sensitivity and specificity. Therefore, development of modern and effective non-invasive methods for detection of trematode infections with high sensitivity and specificity, including screening in endemic regions, is relevant.

The present review analyzes the results of 90 clinical trials and experimental studies on the diagnosis of trematode infections using the PubMed search engine and the eLibrary database. The review analyzes original articles published from January 1, 2015 to December 31, 2021.

Most studies confirm that the absence of a standard diagnostic approach highlights obvious convenience of utilizing a combined approach to reliable diagnosis of trematodiasis. An adequate combination of different diagnostic tests makes it possible to diagnose the disease correctly, devise a correct treatment and follow-up strategy, and organize preventive measures.

The review presents data on the effect of neutrophilic bronchial inflammation on the clinical course, external respiration, and formation of the airway response to cold air in patients with asthma. According to the results of modern studies, activation of the structural and functional state of neutrophils in a mixed inflammatory pattern is associated with an increase in disease severity, more difficult achievement of asthma control, pronounced impairment of bronchial patency due to stimulation of epithelial destruction and remodeling, and development and maintenance of cold-induced airway hyperresponsiveness.

The mechanisms activating the Th1 cytokine profile and oxidative and halogenation stress and determining the activity of neutrophils and persistence of chronic inflammation lead to oxidative damage to lung parenchyma and epithelial dysfunction, which contributes to cold-induced bronchoconstriction. Cytolysis and NETosis, acting as alternative pathways of neutrophil death in the airways of asthma patients, are considered in terms of final stages of induced activity of neutrophil lysosomes in the mixed asthma phenotype.

A significant issue for global healthcare is recruitment and retention of doctors and nurses, especially in rural areas. It threatens continuity and accessibility of medical care for a large segment of the population.

The aim of this article was to summarize currently available data on healthcare recruitment practices, particularly in rural areas, and key factors influencing retention of healthcare professionals. This will allow to develop evidencebased strategies for recruitment and retention of healthcare workers in the Russian Federation and reduce personnel shortage. International and Russian full-text articles were searched for in PubMed, ScienceDirect, Cochrane Library, Google Scholar, and eLibrary databases.

All the studied factors influencing recruitment and retention of healthcare professionals in rural areas were grouped into four main categories: financial, social, professional, and personal. Modern healthcare recruitment strategies were divided into three groups: financial, organizational, and instructional.

The review results suggest that the Russian Federation uses the majority of global strategies to recruit and retain healthcare professionals in rural areas. However, there are some activities that have not been adopted in our country. They may be included in healthcare management practices to increase the effectiveness of regional programs for development of human capital in healthcare.

The article presents a clinical case of a 51-year-old patient first seeking medical care with complaints of paroxysmal cough bringing up bronchial casts. The diagnosis of plastic bronchitis was verified. The disease which has not been well described in the literature, difficulty of verifying the underlying diagnosis due to polysymptomatic clinical presentation characterized by the mortality rate of 50–80%, COVID-19 coinfection, resistance to therapy, and little concern of medical specialists determine the relevance and value of this clinical case.

(COVID-19). In addition to systemic and respiratory symptoms, SARS-CoV-2 causes neurological disorders, as it is a neurotropic virus. Many scientists assume that SARS-CoV-2 can enter the nervous system through the functional receptor of angiotensin-converting enzyme 2, which is present in glial cells, neurons, skeletal muscles, and other organs. Neurological complications are manifested by damage to the central nervous system, peripheral nervous system, and cranial nerves, as well as by mental disorders. Mental illnesses develop due to neuroinflammation and neuronal death after brain infection with SARS-CoV-2.

The article describes a clinical case of a 63-year-old man with the co-occurring novel coronavirus infection and obvious mental disorder who has never had any mental illnesses before. The given clinical example demonstrates the importance of studying the cause-and-effect relationship between COVID-19 and mental illness. In the mediumand long-term perspective, COVID-19 is expected to result in mental health disorders during COVID-19 recovery. Besides, an increase in the number of patients with mental disorders who were mentally healthy before COVID-19 infection is also expected.

Aim. To describe best practices in using human normal immunoglobulin in patients with immune-mediated neurological disorders according to the data of one clinical center.

Materials and methods. From 2016 to 2021, 20 patients with various autoimmune disorders of the peripheral and central nervous system were treated with human normal immunoglobulin at the Neurology Unit No.1 of Pavlov First Saint Petersburg State Medical University. Treatment efficacy was assessed by changes in the neurological examination data according to specialized scales for specific diseases or clinical manifestations (INCAT, QMGS, MoCA, EDSS). Safety of the therapy was assessed considering the instructions to the drug.

Results. In the vast majority of patients, treatment allowed to stabilize the course of the disease or was accompanied by pronounced regression.

Conclusion. The considered clinical cases of the use of human normal immunoglobulin preparations demonstrate the possibility of their use in the treatment of a number of autoimmune neurological diseases for unregistered indications.