New prognostic criterion for the outcome of pregnancy in patients with threatening preterm birth.

To identify new criteria for predicting the outcome of pregnancy in women with threatened preterm labor based on the establishment of the characteristics of differentiation and functional activity of memory T-cells in the population of CD8 + T-lymphocytes. The study involved 56 women with threatened preterm labor at 22-34 weeks of pregnancy. Depending on the outcome of pregnancy, patients were divided into 3 groups: Group I included 22 women by premature labor; group II - 34 women whose pregnancy ended by deliver at term. By tricolor flow cytofluorometry method the content of peripheral Tn, Tcm, Tem and Temra cells in CD8+ population was studied. Statistical analysis was carried out using programs «Statistica for Windows 13.0¼, «Microsoft Excel 2019¼ and «MedCalc 19.3¼. Patients with the threat of preterm birth were characterized by a significant increase in the relative content of CD8+ T-lymphocytes in the peripheral blood compared to the control group (p=0.001). When comparing this indicator in the subgroups of women with the threat of preterm birth, it was found that preterm birth was associated with significantly higher relative CD8 + lymphocyte counts (p=0.03) compared to the indicators of the subgroup of women who gave birth on time. When evaluating the results obtained, it was found that the percentage of CD8+Temra GranzymeB-producing cells in the group of patients with threatened preterm birth, whose pregnancy ended in preterm birth, was significantly lower than in the group of women who gave birth on time (p=0.003). The content of Tcm, Tem memory cells producing GranzymeB in the subgroups of women with pregnancy outcomes of timely and preterm birth did not have significant differences compared to the control group. Thus, the prediction of preterm birth is possible with a value of GranzymeB-producing CD8 + Tem equal to 8.2% or less (sensitivity-87.9%, specificity-85%, accuracy-87.9%). Thus, the identification of a new criterion will make it possible to predict preterm birth in a timely manner and promote the choice of optimal pregnancy management tactics, reasonable prevention of fetal respiratory distress syndrome and transfer of a woman to an obstetric hospital designed to provide high-tech care to premature newborns.

[The awareness and attitude of adolescents concerning healthy life-style].

The authorship's questionnaire "Awareness of adolescents about healthy lifestyle" was applied to carry out sociological survey. The sampling consisted of 183 teenagers aged 15-17 years studying in secondary schools of Ivanovo. It is established that the majority of adolescents are aware of healthy lifestyle. However, for for healthy life-style they take low preventive medical activity, presence of harmful habits, violations of rules of healthy diet and daily regimen, safe life activities, long-term use of gadgets with preference for passive pastime. Only one-third of respondents maintain active lifestyle that denotes the necessity to include these issues in programs of improving competence of adolescents in healthy lifestyle. The revealed absence of conviction in necessity to maintain one's own health and physical conditions conditions necessity to expand information that "unhealthiness" always means restriction of in active lifestyle, sport activities, career choice, future procreation and social activities. The revealed difficulties of observing day regimen, proper diet, sufficient staying outdoor and duration of computer use testify not only higher academic load and poor orderliness, but also weak motivation to observe healthy lifestyle that must be considered in motivation development. The choice of sources informing adolescents about healthy lifestyle issues is to consider that for adolescents the most frequent information sources are the Internet and parents. Besides, it is important to increase role of medical personnel of polyclinics and schools in increasing knowledge of adolescents about healthy lifestyle.

Technologies for Prediction of Preeclampsia.

The aim of the study was to develop technologies for predicting the development of preeclampsia (PE) based on biomedical and molecular-genetic predictors and the calculation of individual risks for this pregnancy complication. MATERIALS AND METHODS: The study involved 457 pregnant women. Of them, 147 women had chronic arterial hypertension (CAH); 109 pregnant women had CAH and secondary preeclampsia (PE); 201 patients had PE. The control group consisted of 105 pregnant women without hypertensive disorders or proteinuria. We performed a retrospective analysis of gestation course and labor outcomes, calculated risk factors using the Open Epi system and logistic regression method. Polymorphisms of genes controlling the vascular tone were identified in venous blood. RESULTS: There were identified risk factors for developing PE, including those in women with CAH: chronic pyelonephritis; baseline mean AP above 95 mm Hg and diastolic AP above 80 mm Hg; body mass index over 30; family history of arterial hypertension. The following were identified as additional predictors of PE: perinatal loss; premature labor; spontaneous miscarriage; PE and closed craniocerebral injuries in the past medical history; threatening miscarriage in the first trimester. Additional risk factors for PE in women with CAH were found: lack of regular antihypertensive therapy before pregnancy and in the first trimester; chronic gastritis; first pregnancy; tobacco smoking.Polymorphic variants of the NOS3 (-786)C allele in the genotype in combination with the heterozygous genotype in the AGTR2 1675G/A gene are associated with a high risk of CAH. The presence of alleles NOS3 (-786)T/C and NOS3 (-786)C, as well as a combination of alleles NOS3 (-786)C and NOS3 894G/T, is associated with PE. The presence of alleles AGT 704C, CYP11B2 (-344)T, and GNB3 825T/T in the genotype, both individually and in combination, is a risk factor for the development of PE secondary to CAH. The data obtained made it possible to develop a method for predicting the onset of PE in women with CAH and a model for calculating the individual risk of PE, which formed the basis for a computer program. CONCLUSION: Calculating the individual risks of PE using the technologies proposed by the authors allows identifying pregnant women belonging to the high-risk group on a timely basis, which ensures high-quality implementation of preventive measures, provides a personalized approach and the possibility to prove the need for additional examination of this category of patients.

Ð rediction of the outcome of pregnancy in women with reccurent miscarriage.

To determine the relative content of monocytes in the peripheral blood producing IL-4, IL-6, IL-10, IFNγ, to identify new criteria for predicting abortion before 22 weeks of gestation in women with the threat of early termination and recurrent miscarriage. Materials and methods. A survey of 91 women in the gestation period of 5-12 weeks was carried out. The main group consisted of 59 women with recurrent miscarriage and the threat of early termination at the time of the study. Depending on the outcome of pregnancy, the main group was subdivided into 3 subgroups: subgroup I - 44 women whose pregnancy ended in timely delivery, II - 8 women who had preterm labor, III - 8 women with termination of pregnancy up to 22 weeks ( missed pregnancy or spontaneous miscarriage). The control group consisted of 32 women with uncomplicated pregnancy. The relative content of IL-4 +, IL-6 +, IL-10 +, IFNγ + monocytes was determined by flow cytometry on FACSCanto II (Becton Dickinson, USA). In women with threatened early miscarriage and recurrent miscarriage, the percentage of IL-4 + and IL-10 + cells in the population of peripheral monocytes is significantly lower, while IL-6 + cells are higher compared to the control group (p = 0.0001 in in all cases), no statistically significant differences were found in the percentage of IFNγ + cells (p = 0.076). A retrospective analysis revealed that in the group of women with termination of pregnancy up to 22 weeks, there was a significant decrease in IL-10 + monocytes in the peripheral venous blood. Prediction of termination of pregnancy before 22 weeks of gestation is possible with a relative content of IL-10 + monocytes equal to 27.0% or less (sensitivity 87.5%, specificity 95.2%, accuracy 93.1%).

Role of CD20 + IL-10 + B-lymphocytes in immunoregulatory processes in women with reccurent miscarriage.

To determine the level of CD20 + IL-10 + B-lymphocytes in pregnant women with the threat of termination of pregnancy at 5-12 weeks and recurrent miscarriage in history and compare the data obtained with the end of gestation. A survey of 65 women at a gestational age of 5-12 weeks was carried out. The main group consisted of 33 women with a threatening recurrent miscarriage at the time of the examination, the comparison group consisted of 10 pre-pregnant women with a threatening sporadic miscarriage at the time of the examination, the control group consisted of 22 pregnant women without signs of a threatening miscarriage. The main group, depending on the outcomes of pregnancy, is divided into 2 subgroups: subgroup A - pregnancy ended in undeveloped pregnancy or miscarriage (9 women), subgroup B - pregnancy ended in childbirth (24 women). The relative content of CD20 + IL-10 + B-lymphocytes was determined by flow cytometry on FACSCanto II (Becton Dickinson, USA). Women in the main group had a significantly lower level of CD20 + IL-10 + B-lymphocytes in comparison with the rest of the surveyed. A retrospective analysis revealed that among women of subgroup A there was a sharp decrease in CD20 + IL-10 + cells compared with subgroup B. Prediction of a non-developing pregnancy and spontaneous miscarriage up to 22 weeks of gestation in pregnant women with threatened spontaneous miscarriage and a history of recurrent miscarriage is possible with the relative content of CD20 + IL-10 + equal to or less than 4.5% (sensitivity 100%, specificity 82.6%, accuracy 87.9%).

Character of ß-lymphocytes differentiation in women with hypertensive disorders during pregnancy.

The aim of the work was to identify the features of B-lymphocyte differentiation in women with hypertensive disorders of various origins, to establish their relationship with indicators of the elastic properties of the vascular wall, and to develop additional diagnostic criteria for the severity of preeclampsia. We examined 193 women at 24-40 weeks of gestation. Of these, 39 women with chronic arterial hypertension, 35 women with preeclampsia that developed against the background of chronic arterial hypertension, 55 with preeclampsia. The control group consisted of 64 women without hypertensive disorders. To assess the elastic properties of the vascular wall, a sphygmographic attachment of the "Poly-Spectrum-8" hardware-software complex ("Neurosoft" Ivanovo) was used. The relative content of B-lymphocytes (CD19 + and CD20 +), regulatory B-cells (CD20 + IL-10 +), switched (CD19 + CD27 + IgD-) and non-switched (CD19 + CD27 + IgD +) memory cells, plasma cells (CD19 + CD20-CD38 +) in the general population of B-lymphocytes was assessed by flow cytometry on a FACSCantoII flow cytometer using the FACS Diva program. Statistical analysis was carried out using the programs "Statistica for Windows 6.0", "Microsoft Excel 2010" and "MedCals". All subjects with hypertensive disorders showed an increase in the stiffness of the arteries of the muscular and elastic types, the most pronounced in the groups of patients with PE, the maximum in women with CAH and associated PE. An increased level of B1-lymphocytes in the peripheral blood is also noted in all hypertensive disorders. There were revealed positive correlations of high strength between: the level of CD20 + cells and the velocity of pulse wave propagation through the arteries of the muscular type (PWVm) in all groups with hypertensive disorders; the content of B1 cells and PWVM in moderate preeclampsia; level emory B-cells and PWV in elastic-type arteries in women with CAH and associated PE. The ROC analysis of the relative content of B1 cells in the general population of B lymphocytes and the content of IL-10-producing cells in the population of CD20 + lymphocytes (Breg) in women with moderate and severe PE revealed criteria for the differential diagnosis of preeclampsia of varying severity. The presence of hypertensive disorders of various origins is accompanied by a decrease in the elasticity of the arterial vascular wall, which is most pronounced in patients with CAH and associated PE. These changes are largely correlated with the level of B cells. As additional criteria for determining the severity of PE, the relative content of B1 cells and IL-10-producing cells in the population of Breg CD20 + lymphocytes can be used.

[New early prognostic criteria for pregnancy outcome in women with recurrent miscarriage.]

To determine the new criteria for predicting the outcome of pregnancy in women with habitual abortion based on features of differentiation of naive T cells and memory cells in a population of T-helper (CD4+) and cytotoxic T lymphocytes (CD8+). The study involved 61 women with threatened and habitual abortion in the first trimester of gestation. Depending on the outcome of pregnancy was allocated to 3 groups: I went to 39 women whose pregnancy ended in timely delivery; in II - 10 women whose pregnancies ended in premature birth; in III - 11 patients in whom there was a spontaneous miscarriage. Using three-color flow cytometry as peripheral venous blood in populations of CD8+ and CD4+ determined by the content Tn, Tcm, Tem and Temra cells. Statistical analysis was carried out in the program «MicrosoftOffice 2010¼, «Statistica for Windows 6.0¼ and MedCalc¼. When conducting a retrospective assessment, it was found that in the group of patients whose pregnancy ended in preterm delivery, the percentage of CD4+ Tem memory cells was significantly higher and CD4+ Tn lower than in the subgroup with timely delivery (p = 0.013 and p = 0.025, respectively ) In patients with early spontaneous miscarriage, the level of CD8+ Tn significantly decreased against the background of the growth of CD8+ Tem memory cells compared with the same parameters in patients with timely delivery (p = 0.040 and p = 0.014, respectively). Prediction of spontaneous abortion is possible up to CD4+ Tn equal to 34.2% or less (sensitivity - 100.0%, specificity - 56.4%, accuracy - 63.8%), premature birth - if the CD4+ Tn equal to 35, 2% or less (sensitivity - 66.7%, specificity - 74.4% accuracy - 72.9%). Thus, the new criteria will allow additional time to identify risk and assign adequate treatment aimed at prolonging the desired pregnancy.

[Peculiarities of the content of peripheral blood cytokines in pregnant women with a habitual miscarriage.]

A lot of research nowadays is dedicated to the problem of habitual pregnancy loss, and this attention is dictated by the continued high frequency of this condition. The pathogenesis of habitual pregnancy loss is very complicated and includes many factors, at present especially close attention is paid to immune aspects. It is considered, that cytokine imbalance might play a key role in the pathogenesis of habitual pregnancy loss. Examination of 38 pregnant women was carried out at 5-12 weeks of gestation. The main group consisted of 17 women with habitual miscarriage and the threat of interruption at the time of the examination, the control group consisted of 21 women with uncomplicated pregnancy and a favorable obstetric history. As the material for investigation peripheral blood was used. Serum level of a complex of cytokines IL-ß, IL-2, IL-4, IL-5, IL-6, IL-9, IL-10, IL-12p70, IL-13, IL-17A, IL-18, IL-21, IL-22, IL-23, IL-27, IFNγ, TNFα, GM-CSF was assessed on the Luminex 200 multiplex fluorescence analyzer (Luminex Corporation, USA). The significant differences in the serum level of IL-1ß, IL-22, IL-23 и IL-27 were observed between the groups, in the main group their level was higher comparing to that of healthy pregnant women. When evaluating the cytokines serum level, fairly high values of IL-27 (in 25%of cases) (p<0,05), TNFα - (in 18% of cases) (p>0,05) were found in the main group, while in the control group they were not registered. Significant differences in the serum level of IL-2, IL-4, IL-9, IL-12p70, IL-18 and IFNγ were not noted in the compared groups (p>0,05). The simultaneous increase in the serum level of pro- and anti-inflammatory cytokines observed in our study can be explained by both an increase in the immune response and triggering of fetoprotection mechanisms. Inadequate cytokine regulation may be a prerequisite for the development of conditions for the development of a threat of termination of a real pregnancy in women with habitual miscarriage.

[The evaluation of efficiency of application of axillary reproductive technologies on the territorial level].

The problem of estimating the frequency of the use of and their effectiveness is considered on the example of the subjects of the Central Federal District of the Russian Federation. The results of analysis of official statistics are presented, which made allowing to establish, that the activity of subjects of the Russian Federation in the use of assisted reproductive technologies has significant differences in the frequency of procedure and their effectiveness. The criteria for comparative assessment of the effectiveness of the organization of medical care for infertility with the use of ART at the territorial level are proposed.

[Method for predicting perinatal hypoxic lesions of the central nervous system in newborns.]

Perinatal lesions of the Central nervous system (CNS) in newborns occupy a leading place in the structure of perinatal morbidity and subsequent disability of children. To identify the features of the content of sRAGE in pregnant women with threatening preterm labor (UPR) in the period of 22-27 weeks, who subsequently gave birth to children with perinatal CNS lesion. Serum of venous blood of pregnant women with UPR at the term of 22-27 weeks was determined by ELISA once the content of sRAGE. If the value of sRAGE in pregnant women is 659.5 PG/ml or less, perinatal hypoxic lesions of the Central nervous system in newborns are predicted with an accuracy of 75.8% (sensitivity of 82.6%, specificity of 66.7%).

[Relationship between activation of endometrial CD56+ natural killers and the character of leiomyoma nodules growth in patients with uterine leiomyoma.]

In patients with different clinical variants of uterine leiomyoma (large or small size, presence or absence of intensive proliferation of tumor cells) the comparative analysis of endometrial CD56+ natural killers (NK) activation was carried out. The relative content of CD56+ cells, expressing of CD158a and CD158i molecules from KIR (killer immunoglobuline-like receptors) family, interferon γ (IFNγ) and transforming growth factor ß1 (TGFß1), was estimated by flow cytometry method. It was found that in the endometrium of all patients with uterine leiomyoma independently of tumor size the content of CD56+ cells and the amount of NK, expressing both activating (CD158i) and inhibitory (CD158a) receptors, were increased. In group of women with stably small uterine leiomyoma the amount of CD56+IFNγ+ lymphocytes was increased, and in women with rapidly growing tumor the elevation of NK, expressing TGFß1, was noted. Differential analysis of data in patients with large leiomyoma in dependence of type of leiomyoma growth was shown that in patients with the high level of tumor cells proliferation the amount of CD56+ NK and the ratio of NK with activating and inhibitory receptors were lower and the content of CD56+TGFß1+ lymphocytes was higher than that in women with leiomyoma, which grew due to accumulation of the extracellular matrix components. Received results showed on the suppression of cytotoxic activity of endometrial NK in patients with uterine leiomyoma with increased proliferation. These changes can be used as additional diagnostic criteria of type of leiomyoma growth.

[Immunomorphological aspects of miscarriage at late gestational ages].

AIM: to reveal the morphological features of placentas and to define a role of the lectin pathway for activation of the complement system in the development of premature birth. MATERIAL AND METHODS: A complex morphological study was conducted to examine 37 placentas, 25 of which were obtained from women with clinical signs of threatened miscarriage and 12 placentas from apparently healthy pregnant women. RESULTS: Placental tissue CD59 expression was ascertained to be significantly less in the women with threatened miscarriage than in those having full-term babies. CONCLUSION: Decreased CD59 expression in threatened miscarriage at late gestational ages leads to additional activation of a maternal immune response and serves as a possible predictor for premature birth.

[The characteristics of function of endothelium in premature neonates with respiratory distress-syndrome].

The examined sampling consisted of 637 premature neonates in early neonatal period at 1-3 and 5-8 days of life. The analysis was applied to indices characterizing epithelium condition and regulating its function. It is noted that in premature neonates with respiratory distress-syndrome of derangement of regulation of function of endothelium are accompanied by increasing of hemostatic disorders and is characterized by increasing of thrombogenic and adhesive characteristics, decreasing of levels of VEGF, higher content of nitric oxide in the form of nitrites, cytokinemia and activation of complement systems.

Comparison of treatment options for experimental endometriosis in rats.

The effectiveness of surgery, immunomodulator "Vilon" therapy, and their combination in the treatment of experimental endometriosis in rats was assessed by the parameters of reproductive function. The experiments demonstrated that surgery combined with intraperitoneal application of "Vilon" is a promising option in the treatment of endometriosis.

[Immunohistochemical changes in the lungs from fetuses and newborn infants at 20- 40 weeks' gestation with false left-sided congenital diaphragmatic hernia].

OBJECTIVE: to study changes in the expression of growth factors in the lungs from fetuses and newborn infants at 20-40 weeks' gestation with false left-sided congenital diaphragmatic hernia (CDH). MATERIAL AND METHODS: Lung fragments obtained at autopsies were examined using immunohistochemically stained paraffin sections. The expression indices of insulin-like growth factor-1 (IGF-1), platelet-derived growth factor (PDGF), epidermal growth factor (EGF), and transforming grow factor-ß (TGF-ß) in the fetal lung sections were compared with the results of survey and elective staining techniques, the morphometric data of digitized lung sections, and the indicators obtained in the comparison group. RESULTS: Morphofunctional changes in the connective tissue, pulmonary vessels, and bronchial and alveolar epithelium at 20-24, 25-27, and 28-40 weeks' gestation were characterized, partly explaining the development of bilateral pulmonary hypoplasia in CDH. There was evidence for the involvement of PDGF, IGF-1, and EGF in primary pulmonary hypoplasia. PDGF deficiency plays a certain role in secondary pulmonary hypoplasia. CONCLUSION: The findings can be used in researches and in the practical work of pathologists and forensic medical experts.

[Primary cardiomyopathies].

The paper provides a review of literature on primary cardiomyopathy yet referring to as an inadequately studied abnormality that is diagnosed with difficulty by clinicians and frequently missed by pathologists at autopsy.

[Psychological features of mothers bringing up disabled children].

BACKGROUND: Research objective was to define psychological makers of mothers bringing up disabled children for scientific justification of the family psychotherapy branches. PATIENTS AND METHODS: 60 mothers bringing up children of early age with infantile cerebral palsy and 50 mothers of children with compensation of perinatal affections of the central nervous system by the 1 life year are surveyed. Personal characteristics, family orientations of mothers, child and mother relations, awareness of mothers on the children health state and the attitude to their rehabilitation were studied by means of psychological techniques. RESULTS: It is found out that the mothers bringing up disabled children more often have emotional disorders, negative attitude to divorce and give the leading role in a family to the husband less often they show hypoguardianship of the child than the mothers of children with compensation of perinatal affections of the central nervous system. Mothers are less satisfied with the child development, they are more often worried about disorders of development of movements, speech and mental development delay, small appetite of the child, they feel helplessness in rehabilitation more often, note the ambiguity of its prospects. They understand that their child needs the help of the qualified experts: neurologist, orthopaedist, logopedist, psychologist, but they aren't satisfied with communication with them more often, underestimate own role in rehabilitation. CONCLUSION: The revealed characteristics prove the necessity and define the main directions of family psychotherapy--correction of mother's emotional disorders, child and parental relations, increase of medical and psychological competence that allows to increase efficiency of rehabilitation.

[Morphological changes in ventricular germinal zone and neocortex of the cerebral hemispheres in human fetuses and newborns on weeks 22-40 of prenatal development].

In this study, we investigated the morphology of the ventricular germinal zone and neocortex of the cerebral hemispheres in the projection field no. 4 of the motor area in human fetuses in dynamics from week 22 to 40 of fetal development. Morphological study allowed us to clarify the following patterns of prenatal ontogeny of the human CNS. On weeks 22-27, an intensive formation of the main sulci of the first order, differentiating the brain into lobes, is observed. By weeks 28-32, the formation of all sulci of the first order is completed; and on weeks 33-37, additional sulci characteristic of an individual are formed. The spurt of gyrification of the cortex (weeks 22-27) practically coincides with the completion of neuronal differentiation and formation of the motor neocortex. The structure of the latter is characterized by a clear stratification of cytoarchitectonic layers and modular organization of neurons with their vertical orientation in cell columns (weeks 25-27). In subsequent weeks of prenatal development until birth, no significant changes in the topography and structure of the neocortex are observed. Structural rearrangement of the ventricular germinal zone on weeks 22-40 of prenatal development consists in its gradual reduction and is completed on weeks 37-40. The criteria of physiological reduction of this area are the zonal location of glioblasts and a progressive decrease in its thickness on weeks 33-37 of prenatal development.