The bidirectional relationship between cerebral structures and the gastrointestinal tract involving the microbiota embraces the scientific concept of the microbiota-gut-brain axis. The gut microbiome plays an important role in many physiological and biochemical processes of the human body, in the immune response and maintenance of homeostasis, as well as in the regulation of circadian rhythms. There is a relationship between the higher prevalence of a number of neurological disorders, sleep disorders and changes in the intestinal microbiota, which actualizes the study of the complex mechanisms of such correlation for the development of new treatment and prevention strategies. Environmental factors associated with excessive light exposure can aggravate the gut dysbiosis of intestinal microflora, and as a result, lead to sleep disturbances. This review examines the integrative mechanisms of sleep regulation associated with the gut microbiota (the role of neurotransmitters, short-chain fatty acids, unconjugated bile acids, bacterial cell wall components, cytokines). Taking into account the influence of gut dysbiosis as a risk factor in the development of various diseases, the authors systematize key aspects and modern scientific data on the importance of microflora balance to ensure optimal interaction along the microbiota-gut-brain axis in the context of the regulatory role of the sleep-wake cycle and its disorders.

Atopic dermatitis (AtD) is a multifactorial inflammatory skin disease characterized by itching, chronic recurrent course and age-related features of lesions. AtD pathogenesis has not been fully elucidated yet. An important factor for AtD emergence and progression is the imbalance in symbiotic microbiota. The research publications provide a few studies about a role for oropharyngeal microorganisms in AtD immunopathogenesis. The aim of the study is to analyze biological diversity of oropharyngeal microbial communities in varying AtD severity. 97 male patients, aged from 16 to 19 years, with different AtD severity were included in the study. Culture study of oropharyngeal discharge was also performed. Biological material was seeded on the expanded list of growth media and incubated for 5 days at the 37°С. To assess the biological diversity of the oropharyngeal microbiota, the coefficient of constancy (C) was used, in order to classify individual microorganisms as permanent, additional or transient. Statistical data processing was performed using the Stat Tech software (version 4.0.0, Stattech LLC, Russia). While examining biological diversity of the oropharyngeal microbiota in AtD patients, 58 microbial species were isolated and identified. After statistical analysis the significant differences in frequency of isolation, depending on different AtD severity were observed for microbes such asStreptococcus vestibularisandRothia dentocariosa. WhenR. dentocariosais isolated from the oropharynx, the chances of AtD exacerbation emergence decreased by 6 times, whereas in case ofS. vestibularis, on the contrary, it increased by 5 times. Therefore, identification of transitions of individual microbes from transient to additional and permanent microbiota and vice versa, depending on the AtD stage and severity, allows to analyze an influence of specific microorganisms in AtD pathological processes and to establish definite new microbiological predictors of AtD exacerbation and remission.

To date, vaccination is an effective means of combating measles, allowing not only to control this infection, but also to raise the question of its elimination. However, there are groups of susceptible individuals in whom, despite the correct and timely administration of the vaccine, a sufficient level of specific antibodies is not formed, or is quickly lost. Lack of immunity after vaccination is a risk factor for both the healthcare professional himself and his patients and colleagues. The article presents data on the state of measles humoral immunity in healhtcare workers of a multidisciplinary hospital. The study was conducted on the basis of the clinical diagnostic laboratory of the Clinics of Samara State Medical University. 759 people were examined - medical workers of surgical, therapeutic, diagnostic departments,intensive care and intensive care units, rehabilitation departments. Also, based on data on the dynamics of changes in parameters of serum at various stages of measles immunization, constructed mathematical models that can be used in predicting primary and secondary vaccination failures. The authors believe that the biochemical processes accompanying the synthesis of specific antibodies require more detailed study, since they may allow detecting metabolic correlates of immune protection that can be used in predicting the effectiveness of vaccination.

Vaccination is the only guarantee for elimination of measles infection. Healthcare workers have a 13- to 19-fold higher risk for contracting measles than the general population. The number of individuals in the population who did not respond to vaccination is up to 10%, and their accumulation may lead to an outbreak of the infection. The aim of our research was to find potential predictors of arising post-vaccination measles antibodies in the panel of biochemical and immunological serum markers in healthcare workers. The group of healthcare workers (n = 76) aged from 19 to 51 years, with proven absence of pre-existing anti-measles antibodies were twice vaccinated 3 months apart with live measles culture vaccine (SPA “Microgen”, Russia). Measles-specific IgG, total IgG, IgM, IgA, IFNγ, IL-6, CRP, total protein, ALT, AST, total bilirubin, urea, creatinine, protein fractions were determined before vaccination, 1 month after vaccination, 1 month following revaccination, 1 year after revaccination. ROC analysis was used to gain access to the diagnostic performance of quantitative variables in predicting a categorical outcome. Development of a predictive probability model for the binary outcome was carried out using logistic regression. IFNγ, total IgG, IgM, total bilirubin, ALT activity at various post-immunization stages may be considered potential laboratory predictors of measles vaccination failures in healthcare workers. Meanwhile, the contents of pre-vaccination IFNγ, and IgG to measles virus after first vaccination proved to be most informative indexes, which formed the basis for the development of regression models predicting the risk of both primary and secondary vaccination failures. These models allowed to develop algorithm for predicting failures of the measles vaccination in healthcare workers that can be used for detection of persons at risk for non-forming specific humoral immunity. This algorithm is primarily focused on search for the persons who have not responded to measles vaccination, including subjects with probable immunodeficiency conditions. We do not exclude that, on the basis of revealed predictors following measles vaccination, it would be possible to build prognostic models of vaccination efficiency for other vaccinemanaged infections.

The severity of complications in cystic fibrosis are determined by microorganisms colonizing the lower airways. Paranasal sinuses can be a reservoir of aggressive pathogens. We have developed a method for collection and primary inoculation of nasal lavage fluid from cystic fibrosis patients for microbiological investigation. As a clinical case illustrating the feasibility of this technique, we describe the dynamics of the microflora composition in a patient with cystic fibrosis. The patient had a clinical and microbiological picture of P. aeruginosa eradication from the lung tissue, owing to which the antibacterial therapy was stopped. Six months later, the microflora in the nasal lavage fluid and sputum were assessed in parallel. The growth of P. aeruginosa (102 CFU/mL) but not P. aeruginosa in sputum was detected. To determine origin of this strain, the degree of genetic relationship between 5 strains obtained from the patient from 2008 to 2016 was assessed based on bacterial protein profiling. A typical strain of P. aeruginosa ATTS 27853 was used as a control. Strains isolated from the patient in 2009 and 2016 were identical suggesting that the antibacterial therapy led to eradication of P. aeruginosa in the lungs, but not in the upper airways. Four months later, the growth of P. aeruginosa was found in sputum. The patient was prescribed to use antibacterial drugs inhaled into paranasal sinuses. Repeated test performed 3 months later resulted in growth of P. aeruginosa 101 CFU/mL from nasal lavage fluid, but not from sputum. The patient was referred to a risk group on airway colonization by pathogen strains derived from the upper airway tract. The clinical example illustrates relevance of conducting a regular microbiological study of nasal lavage fluid in order to early identify clinically significant pathogens to prevent their spread to the lower airway tract.

The review considers questions about the place of laboratory diagnostics in preventive medicine, in particular, about the possibilities of using laboratory methods in controlling the vaccination of infections with an aerosol transmission mechanism (measles, rubella, mumps, chickenpox, influenza, pneumococcal infection, pertussis, diphtheria, COVID-19). The article highlights the main laboratory methods of seromonitoring (enzyme immunoassay, radial hemolysis reaction in gel, dot-immunoassay, antibody avidity determination, hemagglutination inhibition reaction, microneutralization reaction, FAMA, plaque suppression reaction), their advantages and disadvantages. Also presented a block of data on alternative biomarkers (enzymes, lipids, trace elements, hormones, etc.). which serve as potential predictors of vaccination efficacy. The search for new biomarkers of the effectiveness of the formation of post-vaccination immunity opens up new possibilities for predicting the effectiveness of vaccination, which makes their study a promising direction in the field of vaccinology and laboratory immunology.

At present, a search for promising ways to diagnose infection caused by SARS-CoV-2 is quite relevant. Oral fluid is not commonly used for assessment of COVID-19 risk. Its molecular profile reflects both local state of the oral cavity, and individual organs and systems, thus suggesting a reliable diagnostic platform. Systemic inflammatory response is known to play a crucial role in development of the coronavirus infection; the “cytokine storm” determines severity of the disease. The saliva-based diagnostics of clinical course in COVID-19 patients includes determination of IL-6, IL-8, C-reactive protein in oral fluid, in order to assess severity of the inflammatory process. The present study was carried out at the Department of Fundamental and Clinical Biochemistry with Laboratory Diagnostics, and Department of Pediatric Infections at the Samara State Medical University. The study involved 122 persons: 67 clinically healthy individuals comprised the control group, and the group of comparison included 55 inpatients with moderate or severe coronavirus infection (COVID-19) caused by SARS-CoV-2 virus as confirmed by PCR and/or ELISA testing. Development of the disease was accompanied by drastically increased contents of IL-6 and IL-8 in oral fluid of the patients relative to the indexes in healthy persons, i.e., several-fold for IL-6 (+ 650%) and even higher elevation of IL-8 levels (+ 26513%), as well as a 2-fold increase of C-reactive protein (+115%). When comparing the immune indexes of oral fluid in presence versus absence of respiratory insufficiency, a significant difference was found for salivary IL-6 (+173%) in the patients with grade 1-2 respiratory insufficiency as compared with patients free of respiratory disorders. Determination of these proinflammatory markers in patients with COVID-19 is of important prognostic significance when assessing development of the disease and its severity. Direct detection of their content in the oral fluid makes this method relevant, and potentially demanded for the outpatient diagnostics, being highly important during pandemics of coronavirus infection and limited medical resources. Examination of oral fluid at the pre-hospital stage is a resource-saving technology, since it does not require additional medical staff to take biomaterial, is non-invasive to the patient, and suggesting a wide range of research items, it can resolve a number of diagnostic issues, e.c., presence of specific genetic material or antibodies to SARS-CoV-2, severity of the inflammatory process and the risk of respiratory failure in the patient.

Epidemiological situation describing global measles spread is ambiguous. Along with countries succeeded in measles eradication, there are those wherein measles rate remains at quite high level. Because measles is a vaccine-preventable infection, it may then be eradicated solely by ensuring sufficient population coverage with preventive vaccination. The aim of our study was to assess level of measles immunity in medical workers at the Clinics of Samara State Medical University as well as the Samara State Medical University. There were enrolled 1503 subjects (aged 18–79 years), among which all individuals under 55 (77.58%) but not older counterparts provided with medical record on previous measles vaccination or measles infection. Level of serum measles virus-specific IgG antibodies was measured by using ELISA (VektoKor-IgG, JSC Vector-Best, Novosibirsk), with mean concentration ranging in general population within 1.02±0.02 IU/ ml. Positive results were observed in 72.52% of the examined individuals. Average vs. high measles virus-specific IgG level was detected in 52.90% (mean age — 41.4±0.5 years) and 19.62% (mean age — 54.2±0.72 years) of individuals, whereas at level below threshold — in 27.48% of subjects (mean age — 33.25±0.53 years). Thus, in 34.16% of the surveyed vaccinated individuals mostly presented by young subjects contained anti-measles virus-specific antibodies below protective level. Older age groups were shown to increase in average IgG amount with age. Interestingly, age-related measles immunity pattern was observed: percentage of subjects with high vs. low measles virus-specific IgG level increases and decreases, respectively. Taking into consideration a large percentage of subjects previously vaccinated against measles among carriers of low measles immunity, it may be concluded that measles virus-specific IgG antibody level must be monitored in young adulthood to decide of whether subsequent revaccination is necessary.

Laboratory information is an important tool for determining indications for preventive measures and evaluating their effectiveness in healthy individuals. In the instructions for some test-systems for IgG to measles virus, the results of the study are interpreted on the basis of analytical characteristics of the reagents and have no connection with the determination of this indicator in the reference group. At the moment, there is no document setting the protective level of anti-measles Ig G. The aim of the study is to establish reference values of IgG to measles virus by immunoenzyme analysis for health care professionals. The reference group was formed of 299 people and divided into two subgroups: older and under 44 years of age. Reference intervals were calculated according to the CLSI C 28-A3 protocol. The set reference intervals were different from the manufacturer’s stated values. The question arises as to whether the values established by the manufacturer, based on the analytical characteristics of a particular test system, should be used when identifying risk groups of persons with a low level of immunity.

Measles vaccination In Russian Federation was introduced in 1967. It was assumed that the twodose vaccination regime would lead to a decrease in the incidence and elimination of measles. A number of studies have shown that up to 10% of individuals who received two doses of measles vaccine do not develop a specific humoral immunity, or do not maintain it at a protective level. This fact may contribute to gradual accumulation of persons susceptible for measles infection in the population, thus leading to emergence of new viral outbreaks in the future. The aim of this study was to perform dynamic monitoring of the post-vaccination measles immunity. The study involved 149 people. All the examined persons were divided into 2 groups. The group of comparison included persons, aged 19 to 51 years, in whom absence of measles immunity was serologically confirmed (n = 76). This group was twice vaccinated with live measles culture vaccine (NPO “Microgen”, Russia). Determination of IgG to measles virus was carried out 1 month after vaccination and revaccination. The control group consisted of persons with documented evidence of double immunization against measles virus, with laboratory-confirmed measles immunity (n = 73), aged 19 to 53 years. The comparative dynamics of development and contents of antibodies in the comparison-control groups were considered, with respect to the WHO age classification. Basic and postvaccinal dynamic determination of IgG to measles virus in serum was performed by ELISA using the “VectoKor-IgG” test system (Vector-Best, Novosibirsk). When analyzing the results of the study, it was noted that the level of measles immunity group in older persons from control group (over 45 years old) was initially higher, than in younger subjects. Among young people, the titers of specific measles antibodies reached the values of the control group of the corresponding age after the first vaccination, whereas the level of specific measles antibodies in older age group was significantly lower compared to the control group even after revaccination. A month after the first immunization, 4 people did not reach the protective level of anti-measles IgG. However, revaccination allowed them to form anti-measles immunity. In the course of our work, a case of non-response to vaccination was identified. Thus, our study showed a sufficient interindividual variability in humoral immune responses to measles vaccination.

Клиники Самарского государственного медицинского университета, Самара

Самарский государственный медицинский университет, Самара, Российская Федерация (1) Российский университет дружбы народов

Objectives – to compare the parameters of hemostasis in representatives of various blood groups using the ABOsystem. Material and methods. The study involved 51 people (mean age 19.8±0.5 year). The parameters of the coagulation, anticoagulation and fibrinolytic systems were determined for all the examined persons. The following hemostasis parameters were investigated: coagulation factors (II, VII, VIII, IX, X, XI, XII), APTT, prothrombin time, plasminogen, antiplasmin, antithrombin III, protein C. Results. The obtained results indicate the presence of biological variation of blood coagulation parameters depending on the antigenic affiliation of the blood group according to the ABOsystem, which is manifested in a change in the concentration and activity of a number of coagulation factors. The revealed tendencies made it possible to form a coagulation profile depending on the group of blood in the ABOsystem. Conclusion. The study of variability of coagulation parameters, depending on the group of blood in the ABOsystem, is an important step towards the formation of personalized approach in laboratory research.