Effects of Diet-Induced Obesity and Programs for Body Weight Reduction on the Histostructure of the Triceps Surae Muscle in Male Rats.

We studied the effects of visceral obesity induced by a high-calorie diet and health-improving variants of its correction on morphological characteristics of the muscle tissue in male Wistar rats. At stage I, the rats received standard (StD) or high-calorie diet (HCD) for 8 weeks. At stage II, the animals were divided into the following subgroups: no correction (StD and HCD), switching from HCD to StD (HCD/StD) and/or connection of physical activity in the form of treadmill running (StD+running, HCD+running, and HCD/StD+running) for the next 8 weeks. Diet-induced visceral obesity was shown to result in a decrease in the weight of the triceps surae muscle, fatty infiltration, intracellular edema, partial lysis of contractile elements, weak inflammatory response, and decreased muscle fiber area on cross section. Treadmill running (HCD+running) exacerbates the morphological changes, but returns muscle fiber area to normal. Correction of visceral obesity and relative normalization of muscle tissue structure was noted when switching to a standard diet (HCD/StD and HCD/StD+running).

[Eating patterns and risk of eating disorders in adolescents].

Adolescence is a critical period for the onset of eating disorders, which affect an adolescent's diet and can have adverse and long-term health consequences. The relationship between the risk of eating disorders and the diet of Russian adolescents has been little studied. The objective of the research was to characterize the relationship between the risk of eating disorders and dietary patterns in a sample of Russian schoolchildren. Material and methods. The continuous cross-sectional study included tenth-graders of secondary schools (n=379, 63.1% girls) aged 16.0±0.5 years. The Russian version of the Eating Disorder Inventory was used to assess the risk of eating disorders. Dietary information was obtained from questionnaires completed by adolescents, characterizing the frequency of meals (at home and at school) during the week, the variety of dishes, and the frequency of consumption of foods and dishes. Anthropometric measurements were carried out to calculate body mass index (BMI), waist circumference (WC)/height index. Results. The eating patterns of schoolchildren were significantly disrupted, more so in girls. They were statistically significantly less likely than boys to consume meat, milk, nuts, and butter, and were more likely to skip breakfast. Significant correlations were shown between BMI Z-score and WC/height index in girls with body dissatisfaction (R=0.19 and 0.18, respectively, p<0.01), desire to lose weight (R=0.26 and 0.25, respectively, p<0.01) and bulimic tendencies (R=0.13, p<0.05 for WC/height). In boys, the drive for thinness was significantly associated only with abdominal fat deposition (R=0.26, p<0.01). Body dissatisfaction and desire for thinness in boys were associated with statistically significantly lower consumption of candies, chocolate, ice cream, cookies and potatoes; in girls - with rare consumption of candies, ice cream, sweet carbonated drinks, juices, fast food, as well as bread, meat and sausages, butter, skipping breakfast and dinner. Conclusion. The tendency to develop eating disorder in adolescence is more common in girls and is associated with dietary restrictions affecting important components of the diet necessary for normal growth and development.

Endothelin Level in Menopausal Women with Comorbidity of the Acute Phase Middle Severity COVID-19 with Arterial Hypertension and Type 2 Diabetes Mellitus.

The levels of endothelins were assessed in menopausal women with arterial hypertension (AH) and type 2 diabetes mellitus (T2DM) in the acute phase of the moderate COVID-19. Women under observation (age 45-69 years) were divided into two groups. Control group consisted of women (n=16) who did not have COVID-19, were not vaccinated, and had no antibodies to SARS-CoV-2 (IgG). The main group included women (n=63) in the acute phase of the moderate COVID-19 accompanied by pneumonia. According to the clinical and anamnestic data analysis, the main group was divided into subgroups: without AH and T2DM (n=21); with AH and without T2DM (n=32); and with AH and T2DM (n=10). The parameters of clinical blood analysis, as well as endothelin-1, endothelin-2, and endothelin-3 levels were assessed. In women with a moderate COVID-19, the endothelin-1 and endothelin-2 levels were increased compared to the control regardless of AH and T2DM status. We found no statistically significant differences in the studied parameters of endothelial dysfunction between the subgroups of menopausal women in the acute phase of the moderate COVID-19.

Alpha Diversity Indices as Indicators of the Variability of Gut Microbiota in Obese Adolescents of Different Ethnicities.

We compared alpha diversity indices of the intestinal microbiota in adolescents with obesity and normal body weight, taking into account their ethnicity. Intestinal biocenosis was studied by metasequencing of amplicon libraries of V3-V4 fragments of the 16S rRNA gene. The alpha diversity of the microbiota was assessed using classical and alternative indices. Statistically significant differences in intestinal microbiota were observed between Russians with obesity and Buryats with normal body weight, as well as between Russians with obesity and Buryats with obesity when assessing the Shannon-Weaver, Chao1 indices, Faith phylogenetic diversity index, ACE, Fisher, Gini coefficient, Margalef, and Menkhinik indices. It was shown that alpha diversity indices can be used to assess significance of differences and variability of the intestinal microbiota in multifactorial diseases such as obesity in adolescents; however, the scope of application of the criteria should be considered.

The Level of Sex Hormones and Corticosterone in Female Rats during Modeling of Visceral Obesity, Subsequent Physical Activity, and Normalization of the Diet.

The effects of diet-induced visceral obesity and non-drug options of its correction on the level of sex hormones and corticosterone were evaluated in 84 female Wistar rats. During stage I, the rats received either a standard diet (STD) or a high-calorie diet (HCD) for 8 weeks. During stage II, the animals were divided into subgroups depending on obesity correction: without correction (STD control and HCD), transition from HCD to STD (HCD/STD) and/or physical activity (treadmill exercise) for the next 8 weeks (HCD/STD+exercise, STD+exercise, and HCD+exercise). Diet-induced visceral obesity resulted in hyperandrogenization and increased blood corticosterone levels in females. Transition from HCD to STD regardless of physical activity led to normalization of testosterone level and, accordingly, to return to the functional norm of estrogen-androgen balance. The positive effect of moderate physical activity on hormonal status is realized only against the background of a balanced diet or during the transition from HCD to STD.

Oxidative Damage of DNA, Proteins and C-Reactive Protein Parameters in Girls and Boys with Exogenous Constitutional Obesity.

The parameters of oxidative damage of DNA, proteins, as well as the parameters of the thiol-disulfide system and C-reactive protein in adolescent girls and boys with exogenous constitutional obesity (ECO) were evaluated. In girls and boys with obesity, the levels of 8-hydroxy-2'-deoxyguanosine (marker of DNA destruction) were higher than in controls. Evaluation of the activity of the thiol-disulfide system revealed increased levels of oxidized glutathione (GSSG) and decreased levels of the reduced glutathione (GSH) and GSSG ratio (GSH/GSSG) in adolescents with ECO regardless of the sex in comparison with the control. C-reactive protein was also higher in the ECO groups regardless of the sex. The levels of glutathione peroxidase in obese boys were higher than in girls. In view of the revealed shifts, corrective measures with the prescription of drugs with antioxidant properties are recommended in adolescents with ECO to stabilize the indices.

[Neuroendocrine changes among 45-60 years old women with COVID-19 and 12 months after the disease.]

Climacteric women have the post-COVID period clinical features, which can lead to an acceleration of the aging. The study consists in assessing individual parameters of the neuroendocrine system in climacteric women with a moderate course of COVID-19 and 12 months after the disease. Under observation were women aged 45-69 years, who were divided into groups: women who did not have COVID-19, not vaccinated, with no antibodies to COVID-19 (IgG) - control group (n=16); women in the acute phase of COVID-19 with a moderate course, accompanied by pneumonia - main group (n=63); patients from the main group who agreed to be examined 12 months after COVID-19 (n=15). The prolactin, luteinizing hormone (LH), follicle-stimulating hormone (FSH), estradiol, cortisol, testosterone, 17-OH-progesterone, dihydroepiandrosterone sulfate (DHEA-S) levels were assessed. In women with COVID-19 compared with the control the prolactin level was increased (p=0,0002) and the estradiol (р=0,032), testosterone (p=0,004), cortisol (p=0,009), 17-OH-progesterone (p=0,025) and DHEA-S (p=0,003) levels were reduced. Intragroup comparison of hormones showed a decrease in the prolactin level (р=0,041) and increase in the 17-OH-progesterone (р=0,011) and DHEA-S (р=0,0006) levels 12 months after the disease. With a personalized consideration of this group a decrease in the prolactin level is observed in 73,3% of these patients. In the same period, there was an increase in testosterone levels in 46,7% of women, cortisol - in 73,3% of women, 17-OH-progesterone - in 80% of women, DHEA-S - in 100% of cases. When comparing these hormonal parameters between the group of patients who recovered from COVID-19 12 months ago and the control, no statistically significant differences were found, however, patients were identified in whom prolactin and cortisol exceeded the reference values, although in the acute phase of COVID-19 the values of these indicators corresponded to the reference values.

Length of Leukocyte Telomeres in Newborns of HIV-Infected Mothers.

We studied the relative length of telomeres in newborns with unrealized perinatal transmission of HIV (zero viral load according to PCR results). A cross-sectional survey of 62 newborns of HIV-infected mothers (Apgar score 8); the control group consisted of 80 healthy newborns (Apgar score 8). DNA extracted from whole venous blood samples was analyzed. In newborns of HIV-infected mothers, the relative length of telomeres was significantly lower (0.69 (0.66; 0.72)) than in newborns of the control group (1.1 (0.97; 1.22)) (p<0.001). No significant differences in the relative length of telomeres were found between newborns of mothers with a viral load at the time of delivery and with undetectable viral load: 0.69 (0.66; 0.73) and 0.69 (0.63; 0.72). These findings indicate that HIV-infection in mothers or exposure to antiretroviral therapy has an impact on the relative telomere length in leukocytes of newborns.

Online Service with Automated Interpretation of Sequencing Data and Prediction of Pyrazinamide Resistance in Mycobacterium tuberculosis.

Pyrazinamide plays an important role in the treatment of tuberculosis. However, the microbiological test for pyrazinamide resistance is more complex and less reliable than testing of susceptibility to other anti-tuberculosis drugs due to the need to grow the pathogen at pH 5.5. Identification of mutations that cause resistance to anti-tuberculosis drugs can replace microbiological methods. Mutations in the pncA gene are responsible for the main mechanism of the resistance to pyrazinamide and are found in more than 90% of resistant strains. However, the genetic method for determining drug susceptibility is very complex, because mutations leading to pyrazinamide resistance are diverse and scattered throughout the gene. We have developed a software package for automatic data interpretation and prediction of the resistance to pyrazinamide based on Sanger sequencing results. The effectiveness of detection of pyrazinamide resistance in 16 clinical samples was compared using the BACTEC MGIT 960 automated system and pncA gene Sanger sequencing with automated analysis of the results. A significant advantage of the developed method over a single microbiological study was shown, due to greater reliability of the results irrespective of the purity of isolates.

Pro-and Antioxidant Status in Newborn with COVID-19.

There is practically no information on the state of oxidative stress reactions in newborns with coronavirus infections. At the same time, such studies are extremely important and can contribute to better understanding of the process of reactivity in patients of different ages. The content of pro- and antioxidant status indicators was assessed in 44 newborns with confirmed COVID-19. It was found that the content of compounds with unsaturated double bonds, primary, secondary, and final LPO products were elevated in newborns with COVID-19. These changes were accompanied by higher SOD activity and retinol level and reduced activity of glutathione peroxidase. Contrary to popular opinion, newborns can be a COVID-19-susceptible age group and require more close monitoring of metabolic reactions during the period of neonatal adaptation that is an aggravating background during infection.

Features of the Free Radical Oxidation Process and Antioxidant System in Newborns Born to HIV-Infected of Mothers Who Received Antiretroviral Therapies to Prevent HIV Transmission.

The LPO processes and the state of the antioxidant system in perinatally HIV-exposed newborns were studied. Perinatally HIV-exposed (n=62) and healthy newborns (n=80; control) were examined retrospectively (Apgar score 8 in both groups). Blood plasma and erythrocyte hemolysate were used as the material for biochemical tests. Using spectrophotometric, fluorometric, and statistical methods, we found enhanced LPO processes insufficiently compensated by the antioxidant system with excessive accumulation of damaging metabolites in the blood of perinatally HIV-exposed newborns. These changes can be a consequence of oxidative stress during the perinatal period.

Differences in Gut Microbiota Composition and Predicted Metabolic Functions: a Pilot Study of Adolescents with Normal Weight and Obesity.

Understanding the principles underlying the stability and sustainability of the gut microbiome of adolescents with normal weight and obesity will make it possible to implement a personalized approach to the correction of metabolic disorders. The article presents the results of a pilot study of the diversity and metabolic potential of the gut microbiome in adolescents with normal body weight and obesity. Biological material was studied using metagenomic sequencing of the V3-V4 variable regions of the 16S rRNA gene. In all adolescents with normal weight, similar degree of the phylogenetic relationship between the bacterial taxa of the community was demonstrated. In contrast, obese adolescents were characterized by the presence of phylogenetically distinct taxa in the gut microbiota. However, even with differences in taxonomic composition, the gut microbial community can compensate for the absence of certain taxonomic groups by implementing the necessary metabolic functions using other phylogenetically close taxa.

Features of the EEG Pattern of Sleep Spindles and Its Diagnostic Significance in Ontogeny.

Analysis of the microstructure of sleep using extended EEG monitoring can provide deep understanding of the neuronal activity of the brain. Sleep spindles (SS) are one of the main EEG patterns occurring during the non-rapid eye movement sleep. SS reflect the process of synchronization and provide sleep initiation and maintenance by suppressing sensory information. SS are associated with a wide range of brain functions, such as memory and neuroplasticity, general intelligence and cognitive performance, which undergo various changes throughout the life. In this review we discuss the features of the formation and regression of SS in humans during ontogeny on the basis of published data of the last 5-6 years and fundamental results of previous studies at the Scientific Centre for Family Health and Human Reproduction Problems that formed the basis of the modern study of neurophysiological phenomena of the wakefulness and sleep. The search for diagnostic patterns and prognostic markers of the pathology of higher nervous activity remains a priority in fundamental studies and medical practice. Modern methods for studying sleep and its EEG patterns are the next step in understanding the neurophysiological aspects of the sleep-wake cycle. This will open prospects for predicting postnatal maturation, understanding the mechanisms of brain neuroplasticity in the "sleep-wakefulness" continuum, which is one of the tasks of modern somnology and neurophysiology.

Biochemical Status of Obese Male Adolescents of Different Ethnicity: Discriminant Analysis in the Identification of the Most Informative Indicators.

Parameters of the lipid metabolism and lipid peroxidation-antioxidant defense system in male adolescents with obesity, representatives of European and Mongoloid ethnicity were evaluated. Discriminant analysis revealed the most informative biochemical parameters for obese male adolescents: glutathione-S-transferase, VLDL cholesterol, glutathione peroxidase, reduced glutathione, and SOD activity for obese male Caucasian adolescents and glutathione-S-transferase, VLDL cholesterol, α-tocopherol, and glutathione peroxidase for Mongoloids obese male adolescents. The use of discriminant analysis allows implementing a differentiated ethnicity-oriented approach to prescribing antioxidant drugs in the complex therapy of obesity.

Superoxide Dismutase Activity in Male and Female Patients of Different Age with Moderate COVID-19.

The study involved 271 patients (132 men and 139 women) with moderate COVID-19. Superoxide dismutase (SOD) activity in erythrocytes was measured spectrophotometrically. In total group of patients (divided into age groups of 18-35, 36-45, 46-60, and 61-90 years), higher SOD activity was found in the 18-35 age group in comparison with the groups 46-60 years (p<0.01) and 61-90 years (p<0.05). Then, the groups were additionally divided by sex. In men, no differences in enzyme activity were found between the age groups. In women of early reproductive age, SOD activity was higher than in groups 36-45, 46-60, and 61-90 years. The sex differences consisted in higher SOD activity in women aged 18-35 years in comparison with men of this age. These data should be taken into account when choosing the tactics of therapy for patients with moderate COVID-19 course.

Diversity and Metabolic Potential of the Gut Microbiome in Adolescents with Functional Bowel Disorder.

The article presents the results of a pilot study of the diversity and metabolic potential of the gut microbiome in adolescents with various forms of functional bowel disorder. The participants were the patients of the Clinic of Research Center for Family Health and Human Reproduction Problems. Biological material was studied using metagenomic sequencing of V3-V4 variable regions of the 16S rRNA gene. We showed that the composition of the minor component of the intestinal microbiome in adolescents with functional bowel disorder differs from that in the healthy subjects (control). Different types of transit disturbances in functional bowel disorder also differ from each other. According to the metabolic potential, adolescents can be divided into two groups irrespective of the pathophysiological manifestations: for one group, a more intensive metabolism in amino acid and lipid biosynthesis pathways was predicted than for the other.

[Protocol of Transcriptome Analysis of Decidual Placenta Cells].

The advent of high-throughput sequencing technologies has expanded our understanding of the biological significance of non-coding regions of the genome. In recent years, more and more studies have been devoted to studying the role of noncoding RNAs in the development of diseases, as well as their participation in various cellular processes. Until now, all transcriptome studies of native placental tissue with the description of the noncoding RNA region were carried out without isolating individual cell populations. This approach, due to the high cellular heterogeneity of the placental tissue, significantly complicates the ability to determine the molecular-biological functions of individual cells and their role in the molecular pathogenesis of reproductive disorders. In this work, we propose a technique for obtaining total RNA from single decidual cells of frozen placental tissue obtained by laser-capture microdissection technology for transcriptome sequencing, including a cluster of noncoding RNAs. This technique can be successfully used to study the full-genome expression profile of other placental cell populations. The high accuracy of results on the transcriptome profiling of decidual cells obtained using the developed technique was additionally confirmed by an integrative analysis with the results of a 10x Genomics experiment.

[Disorders of lipid metabolism as a risk factor for male infertility].

The presented literature review analyzes and summarizes data on studies by domestic and foreign authors on one of the most pressing problems of modern andrology - the pathogenetic relationship of excess body weight and male infertility. Modern clinical, epidemiological and experimental data indicate a negative effect of obesity on the reproductive function of men. According to the WHO, in Russia 54% of men are overweight, 15% of whom are obese. The problem of obesity is independent of age, area of residence, as well as the social and professional level of men. Obesity is a predisposing factor in the development of concomitant somatic pathological processes. Oxidative stress of sperm, androgen deficiency, neuropathy is far from an exhaustive list of the most important mechanisms for the realization of the neuroendocrine and reproductive effects of overweight and obesity. The increasing number of infertile couples annually dictates the need for a reliable monitoring system to get a correct picture of the development of the obesity epidemic, as well as to quickly assess what preventive measures should be taken.

The relationship between the composition of the microbiota and functional intestinal disorders in obese adolescents.

Functional gastrointestinal disorders (FGIDs) in children and adolescents are one of the most common pathologies of the digestive tract. The aim of the study was to study the structure of the colon microbiota in obese adolescents and to establish its relationship with the clinical manifestations of the disease FGIDs. The study included 20 adolescents aged 11-17 years. The main group included 13 adolescents with a clinically confirmed diagnosis of obesity (the standard deviation of the body mass index (SDS BMI) is more than 2,0) in combination with FGIDs. The control group consisted of 7 adolescents with normal body weight and no abdominal complaints (SDS BMI=0,66). Clinical symptoms from the bowel re diagnosed on the basis of the Rome IV. The consistency of feces was evaluated using the Bristol Stool Form Scale. The study of biological material was carried out by standard bacteriological methods. It is shown that in adolescents with obesity and FGIDs, there is a decrease in the concentration of representatives of bifidoflora, an increase in the microbial density of Escherichia coli with altered properties and an excessive growth of potentially pathogenic enterobacteria. It is established that the presence of conditionally pathogenic bacteria is sem. Enterobacteriaceae is associated with abdominal pain during defecation. In obese adolescents in the group with unformed stools, Clostridium spp was recorded as part of the intestinal microbiota.

The Effect of Polymorphisms of Energy Metabolism Genes on Metabolic Disorders in Overweight Adolescents of Two Ethnicities.

The aim of this cross-sectional observational study is to determine the contribution of polymorphisms of energy metabolism genes into metabolic disorders in Russian and Buryat adolescents with overweight and obesity. The study included 354 Russian and Buryat adolescents aged 13-18 years. Body mass index and serum levels of glucose, insulin, and leptin were measured and insulin resistance index HOMA-IR was calculated. Molecular genetic analysis for the presence of 9 loci of energy metabolism genes LEP, LEPR, POMC, FTO, and MC4R were analyzed. It was found that the risk of metabolic disorders is associated with the presence of polymorphic loci of leptin receptor gene LEPR and melanocortin receptor gene MC4R (LEPR rs1137100+LEPR rs1137101 and LEPR rs1137100+MC4R rs17782313) in Russian adolescents with overweight and obesity and polymorphisms of the gene FTO (FTO rs9939609+rs8050136) associated with fat mass and obesity in Buryat adolescents.