Aim. To assess the effects of reactive oxygen species and nitric oxide on the scar tissue ex vivo.

Materials and Methods. The study was performed using fragments of scar tissue (n = 10) removed intraoperatively in patients with Dupuytren's contracture. Each fragment was divided into 3 equal segments: 1) control; 2) treated with singlet oxygen for 5 minutes; 3) treated with nitric oxide (20 ppm) for 5 minutes. Upon the indicated treatment, we evaluated the dielectric properties of the tissue employing nearfield resonant microwave sensing using a customised software package (Institute of Applied Physics, Russian Academy of Sciences). Then, each segment was homogenised and the parameters of oxidative metabolism (intensity of free radical oxidation and total antioxidant activity) were measured in homogenates by Fe-induced biochemiluminescence.

Results. Treatment of scar tissue fragments by singlet oxygen and nitric oxide altered the dielectric properties of the tissue and the intensity of free radical oxidation. Singlet oxygen action moderately increased the dielectric permittivity of the tissue and rendered a balanced stimulating effect on proand antioxidant systems. Nitric oxide significantly augmented dielectric permittivity and conductivity and raised the antioxidant potential of the tissue.

Aim. To study the correlation of serum persephin with clinical, instrumental and biochemical indicators of brain damage and with an adverse outcome in critically ill newborns.

Materials and Methods. The study included 44 critically ill newborns. Blood samples were collected on the 1^st and 7^th day of life. Brain injury was assessed by recording Apgar score, depression of consciousness and brainstem reflexes in unsedated patients over 7 days of life, convulsions, neurosonographic signs of cerebral edema, serum protein S100B on the 1^st and 7^th day of life, and using indicators of adverse neurological outcome. The correlation of serum persephin on the 1^st and 7^th day of life with signs of brain damage was evaluated using the Spearman's rank correlation coefficient and Mann-Whitney U-test.

Results. No statistically significant correlation was found between the concentrations of serum persephin on the 1^st and 7^th day of life and Apgar score (p = 0.721 and 0.222, respectively), depression of consciousness and stem reflexes (p < 0.05), convulsions (p = 0.673 and 0.432, respectively), cerebral edema (p = 0.737 and 0.558, respectively), and serum protein S100B both on the 1^st day (p = 0.095 and 0.475, respectively) and 7^th day of life (p = 0.988 and p = 0.775, respectively). Further, there was no statistically significant association of the serum persephin on the 1^st day of line with an unfavorable outcome (p = 0.294). Yet, we revealed an association of serum persephin on the 7^th day of life with an unfavorable outcome (p = 0.013), with a cut-off point of 828 ng/mL, a sensitivity of 39%, and a specificity of 100%.

Conclusion. Persephin has poor diagnostic and prognostic significance for assessing the severity of brain damage in critically ill newborns. The obtained data on the correlation of the concentration of persephin for 7 days with an unfavorable outcome are doubtful due to the lack of data on its correlation with signs of severe brain damage.

Aim. To study the ultrastructure of mitral bioprosthetic heart valves (BHVs) which failed due to infective endocarditis.

Materials and Methods. Here we examined 7 ethylene glycol diglycidyl ether-treated xenopericardial BHVs excised during repeated BHV replacement because of prosthetic endocarditis. After being fixed in formalin and postfixed in osmium tetroxide, BHVs were dehydrated and stained in uranyl acetate with the subsequent embedding into epoxy resin, grinding, polishing, and lead citrate counterstaining. Upon the sputter coating with carbon, we visualised the BHV microanatomy by means of backscattered scanning electron microscopy at 15 kV voltage.

Results. The extracellular matrix underwent degradation and disintegration resulting in loosening, fragmentation, and reduction in the electron density of collagen and elastin fibers. We observed a number of recipient cells (macrophages, multinucleated giant cells, neutrophils, endothelial cells and smooth muscle cells) within the BHVs. The highest number of cells was localized on the valve surfaces. The localization of the recipient cells on the ventricular and atrial surfaces was different. The central part of the valves was abundantly populated by macrophages.

Conclusion. Prosthetic endocarditis is accompanied by the migration of recipient cells into the BHV structure, which is the consequence of surface and extracellular matrix disintegration.

Aim. Here, we studied whether the immunoreactivity in pre-operative period defines early postoperative complications in patients with infective endocarditis (IE).

Materials and Methods. We consecutively enrolled 110 patients with subacute IE (80 with native-valve IE and 30 with prosthetic valve IE) who underwent a heart valve replacement, then measuring the levels of IgM, IgA, IgG, and complement components in their serum and evaluating their correlation with an adverse early postoperative outcome.

Results. Compared with patients< 50 years of age, those ≥ 50 years of age had 2-foldand 3-foldhigher prevalence of systemic inflammatory response syndrome and multiple organ dysfunction syndrome in the early postoperative period. Notably, these numbers correlated with increased С3d and С5а along with reduced Ig М and IgG. IgМ below 9.5 mg/mL and IgG below 2.0mg/mL indicated a 3-foldhigher risk of multiple organ dysfunction syndrome (OR = 3.07, 95% CI = 1.96-4.04, р=0,001).

Conclusion. Serum IgM, IgG, and complements factors C3d and C5a may be used as prognostic markers of multiple organ dysfunction syndrome in the early postoperative period.

Aim. Currently, there is no method which accurately predicts an adverse outcome of heart failure with a preserved left ventricular ejection fraction (HFpEF) upon ST-segment elevation myocardial infarction (STEMI). Here we studied the prognostic significance of procollagen type I C-terminal propeptide (PICP) and procollagen type III N-terminal propeptide (PIIINP) in patients with post-STEMI HFpEF.

Material and Methods. The study included 83 patients (60 men and 23 women) with post-STEMI HFpEF (left ventricular EF ≥ 50%) and 20 ageand gender-matched healthy controls. Serum concentrations of PICP and PIIINP were measured on the 1st day of hospitalization using enzyme-linked immunosorbent assay with the following calculation of PICP/PIIINP ratio.

Results. Serum PICP and PIIINP on the 1st day of STEMI significantly (3.4-fold) exceeded the values of the control group and were as follows: PIIINP: 26.0 (18.9; 34.9) ng/mL (р = 0.047); PICP: 609.0 (583.0; 635.0) ng/mL (р = 0.049).

Conclusion. Elevated values of procollagens indicate that cardiac fibrosis commences within the 24 hours after STEMI onset. The pivotal role of cardiac fibrosis in the formation of diastolic dysfunction suggests the usefulness of serum procollagens to predict the development of HFpEF in a long-term period upon STEMI.

Aim. To assess the structure of critical obstetric conditions and maternal mortality in Transbaikal Region in pandemic (COVID-19) and pre-pandemic years (2020 and 2019, respectively).

Materials and Methods. We retrospectively analysed “near miss” (NM) and maternal deaths (MD) in 2019 and 2020, further calculating the severe maternal outcome ratio (SMOR), the summary indicator which includes both NM and MD per 1000 live births.

Results. In a pandemic year (2020), we observed an increase in SMOR in comparison with a pre-pandemic year (3.0 vs 2.0, respectively). In 2019, maternal mortality was exclusively caused by obstetric complications, while extragenital pathology (cardiovascular disease and COVID-19) was responsible for that in 2020. However, the main causes of «near miss» in 2019 and 2020 were similar, including obstetric haemorrhage because of placental abruption and severe pre-eclampsia. Maternal near-miss mortality ratio (MNM/MD) increased from 7.3: 1 in 2019 to 11.3: 1 in 2020, and mortality index (MD/(MNM + MD) × 100) reduced from 12.0 to 8.1. Therefore, fewer women with life-threatening conditions died in 2020 as compared with 2019, indicating a better quality of obstetric care.

Conclusion. Analysis of the critical obstetric conditions can probably find regional issues of maternal healthcare during the COVID-19 pandemic and propel the policy makers to find additional resources to minimise maternal morbidity and mortality.

Aim. To develop a predictive model for calculating the likelihood of recurrent uterine fibroids after myomectomy.

Materials and Methods. We consecutively recruited 149 women aged 19 to 45 years who underwent myomectomy. Prediction of uterine fibroids was carried out using multivariate analysis including a classification tree (IBM SPSS Statistics). To construct a classification tree for predicting recurrent uterine fibroids, the following patient-related parameters were used as the input features: age, family history, nulliparity, past medical history of myomectomy, obesity, rapid fibroid growth, multiple fibroids at myomectomy, BCL-2, Ki-67, and VEGF expression.

Results. When analyzing the resulting classification tree, we can conclude that the most significant factors defining the recurrence of uterine fibroids are low parity, multiple fibroids at myomectomy, intensive VEGF expression, and weak expression of BCL-2.

Conclusion. Our original model allows the identification of the most significant predictors of recurrent uterine fibroids and might be proposed as a useful tool for clinical practice.

Aim. To study the epidemiological and clinical features of COVID-19 among patients with tuberculosis.

Materials and Methods. We studied the incidence of COVID-19 in various population groups in Kemerovo Region in 2020 (from March, 13 to December, 31). The study cohort consisted of 3929 tuberculosis patients, including 113 with a verified COVID-19 diagnosis. The control cohort included tuberculosis-free subjects with COVID-19 (25,774 individuals). Out of these subjects, we enrolled 71 patients with tuberculosis and 71 age- and gender-matched controls. All patients underwent complete blood count, urinalysis, biochemical analysis, and coagulation testing.

Results. The incidence of COVID-19 in patients with tuberculosis was 2.96-fold higher than in the tuberculosis-free population (2876.05 and 971.17 per 100,000 population, respectively). In patients with tuberculosis, the highest incidence of COVID-19 was recorded in two age categories: from 18 to 29 years and ≥ 65 years of age. In tuberculosis patients, COVID-19 was mostly mild, was characterised by a 9.2-fold lower frequency of pneumonia, 11.8-fold less use of antibiotics, and oxygen therapy was required only in 1.41% of cases in comparison with 16.9% in the tuberculosis-free subjects. In addition, patients with tuberculosis less often suffered from hyperthermia, cough and weakness. Regarding the comorbid conditions, patients with tuberculosis showed lower prevalence of arterial hypertension, chronic heart failure, peripheral artery disease, and obesity. Further, patients with tuberculosis generally had higher glomerular filtration rate and rarely had neutrophilia or lymphopenia when compared with the control individuals with COVID-19, although having higher fibrinogen and aspartate aminotransferase serum levels.

Conclusion. Tuberculosis is a risk factor of COVID-19 but not a predictor of morbidity and mortality from this disease.

Aim. To analyse an epidemic process of community-acquired mycoplasma pneumonia in the Volga Federal District and the Nizhny Novgorod Region.

Materials and Methods. We retrospectively analysed statistical reporting forms and electronic databases for 2012-2019 which included 443 cases of community-acquired mycoplasma pneumonia (349 foci and 4 outbreaks). In 2020, we assessed aetiology of community-acquired pneumonia in hospitalized patients of all ages who were diagnosed with a radiologically confirmed pneumonia (152 cases). In 2021, we carried out a microbiological study of pneumonia-causing pathogens in the nasopharynx among the healthy population (325 cases).

Results. Average long-term incidence of community-acquired pneumonia in Nizhny Novgorod Region for 2012-2019 was 3.4 per 100,000 population (95% CI = 0.3-6.5, p < 0.001), with a pronounced upward trend. In general, the aetiology of community-acquired pneumonia in the Nizhny Novgorod Region in 2019 was established at 25.81 ± 0.7% cases. M. pneumoniae accounted for 8.00 ± 0.43% cases (56.72 ± 2.53%) of all aetiologically defined communityacquired pneumonias. In children, the aetiology was determined in 93.1 ± 2.5% cases, of which M. pneumoniae accounted for 13.8 ± 3.5% cases (14.6 ± 3.74% of all community-acquired pneumonias).

Conclusion. Mycoplasma pneumonia is responsible for a significant proportion of all community-acquired pneumonias in Nizhny Novgorod Region. Notably, there is a low detection rate of mycoplasma pneumonia in certain territories that might explain an uneven distribution of associated morbidity.

Aim. To study the gene-specific composition of Borrelia spp. in ixodid ticks inhabiting the foci of ixodid tick-borne borreliosis (ITBB) in the south of Western Siberia.

Materials and Methods. The gene-specific composition of Borrelia spp. in ixodid ticks was determined by inoculation on a BSK-H nutrient medium, real-time polymerase chain reaction, and sequencing (1148 specimens of ixodid ticks collected from vegetation and 2183 specimens withdrawn from humans).

Results. Infection of ticks with borrelia ranged from 22.4% in the Altai Republic to 56.9% in the Novosibirsk Region. There were no significant differences in the levels of Borrelia infection between two major ixodides, I. persulcatus and I. pavlovskiy (average infection levels 40.0% and 38.8%, respectively). At least five gene species of pathogenic Borrelia (B. garinii, B. afzelii, B. bavariensis, B. miyamotoi, and B. spielmanii) have been identified. The GenBank database contains 45 nucleotide sequences of the intergenic spacer rrf (5S)-rrl (23S). Prevalence of gene species B. garinii and B. afzelii in different ticks (I. persulcatus and I. pavlovskiy) did not differ significantly, yet B. garinii was found to be more frequent than B. afzelii. The frequency of infection of I. persulcatus ticks with B. miyamotoi was significantly (3.5-fold) as compared to those of B. garinii and B. afzelii. In D. reticulatus ticks, the DNA of B. spielmanii and B. miyamotoi was detected.

Conclusion. It is necessary to continue studies to assess the role of the meadow ticks D. reticulatus in the circulation of different Borrelia spp. in various natural foci within the Russian Federation.

Application of molecular genetic methods in the diagnosis and treatment of human diseases is extremely wide due to a huge amount of hereditary information contained in the human genome. Gene diagnostics allows establishing predisposition to diseases, identification of genetic abnormalities and prediction of pathological outcomes. In addition, gene diagnostics also enables prediction of the individual response to treatment in order to achieve the maximum therapeutic effect. Among all molecular genetic methods, polymerase chain reaction (PCR) diagnostics is a leading approach. Technical simplicity, low cost, high sensitivity and reliability of the method have made PCR diagnostics a routine modality for the risk assessment, diagnostics, and monitoring of the treatment efficiency. Here, we consider the application of PCR diagnostics for the abovementioned tasks and talk about the real-life examples of detecting mutations and chromosomal aberrations which may cause a disease. Further, we discuss the prospects of using a semi-quantitative PCR in medical practice and focus on pharmacogenetics as a key component of a personalised therapy. The lecture is aimed primarily at biomedical students and physicians and represents a continuation of the previous lectures published in Fundamental and Clinical Medicin.

Persistent multiple organ failure is a new phenotype of a critical patient capable of leveling all the initial successes in treating a patient in the intensive care unit, which is associated with an increase in the need for methods of organ function replacement, the development of cognitive deficits, muscle weakness and polyneuropathy of critical care. A case study is presented that demonstrates the effectiveness of primary resuscitation of a patient with severe polytrauma with further persistence of multiple organ failure and the need for long-term therapy aimed at recovering a critical patient and with an emphasis on drugs affecting cognitive function.