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Background The inhaled lung-selective pan-Janus kinase inhibitor nezulcitinib had favourable safety and potential efficacy signals in part 1 of a phase 2 trial in patients with severe COVID-19, supporting progression to part 2.Methods Part 2 was a randomised, double-blind phase 2 study (NCT04402866). Hospitalised patients aged 18–80 years with confirmed symptomatic COVID-19 requiring supplemental oxygen (excluding baseline invasive mechanical ventilation) were randomised 1:1 to nebulised nezulcitinib 3 mg or placebo for up to 7 days with background standard-of-care therapy (including corticosteroids). Efficacy endpoints included respiratory failure-free (RFF) days through day 28 as the primary endpoint. Secondary endpoints included safety and change from baseline oxygen saturation (SaO2)/fraction of inspired oxygen (FiO2) ratio on day 7, and 28-day mortality rate was a prespecified exploratory endpoint.Results Between June 2020 and April 2021, 205 patients were treated (nezulcitinib, 103; placebo, 102). There was no statistically significant difference between nezulcitinib versus placebo in the primary endpoint (RFF days; median, 21.0 vs 21.0; p=0.6137) or secondary efficacy endpoints. Nezulcitinib was generally well tolerated with a favourable safety profile.Conclusions Although the prespecified primary, secondary and exploratory efficacy endpoints, including RFF through day 28, change from baseline SaO2/FiO2 ratio on day 7, and 28-day mortality rate, were not met, nezulcitinib was generally well tolerated and had a favourable safety profile. Further studies are required to determine if treatment with nezulcitinib confers clinical benefit in specific inflammatory biomarker-defined populations of patients with COVID-19.

Background. Cardiovascular disease (CVD) is one of the main causes of morbidity and mortality among adults worldwide. On another hand, obstructive sleep apnea syndrome (OSAS) is common in patients with CVD, and can worsen the patients prognosis due to late diagnosis. Aim: to analyze and summarize the published researches about interrelation between CVD and OSAS, its influence on CVD, and the effects of continuous airway pressure (CPAP) treatment of OSAS on CVD in order to pay attention to OSAS potential risks, improve the investigation of this syndrome and management. Materials and methods. Review of scientific literature in the international electronic scientometric databases PubMed, Google Scholar by key words for the period 2008-2023. The search was carried out by two independent authors. 150 sources were selected, 48 English–language articles of which met all the search criteria and were used for analysis. Results. OSAS is one of the widespread sleep disorders that frequently occurs in patients with CVD, impairs quality of life. Its increases cardiovascular and all-cause mortality and cardiovascular morbidity. OSAS is observed in patients with arterial hypertension in 30-83%, coronary heart disease in 38-65%, stroke in 57-65%, heart failure in 12-55%, heart rhythm disorders - in 20-50%. In addition, the relationship between OSAS and diabetes, metabolic syndrome, insulin resistance, depression, and cognitive impairment has been established. OSAS is often not diagnosed or not diagnosed in time. Thus, there are data that 86-95% OSAS, clinically manifestated, were missed diagnosis, that worsens the prognosis of such patients. Conclusions. OSAS is a common sleep breathing disorder in patients with CVD that is often diagnosed late. Most studies have shown that OSAS worsens the CVD course and outcomes. Therefore early diagnosis and timely appropriate treatment reduce morbidity and mortality.

African swine fever (ASF) has posed a significant threat to Ukrainian pig farming since its identification in 2012. In this study, recognising the pivotal role of pigkeepers in disease control, we conducted ten focus groups involving 52 smallholders across eight regions in Ukraine. Using participatory methods, we revealed their awareness of ASF signs, transmission routes, preventive measures, and the perceptions of stakeholders involved in ASF control. Furthermore, we identified the smallholders’ acceptance of eradication and restriction measures, the perceived impact of zoning consequences, and their main sources of ASF information. Smallholders identified fever and skin haemorrhage as the most indicative signs of ASF and highlighted rodents as a primary transmission concern. Disinfection was seen as the most effective measure for preventing the introduction of ASF. Pigkeepers who perceived their stakeholder role in ASF control showed more trust in themselves and veterinarians than in central veterinary authorities. Farm-level ASF eradication measures were generally accepted; however, culling within the protection zone was least accepted, with economic losses listed as the most impactful consequence for pigkeepers. For ASF information, pigkeepers favour web searches and veterinarians, as well as traditional media and word-of-mouth news. This study provides valuable insights into refining the ASF communication strategies in Ukraine.

During the COVID-19 pandemic number of patients suffering from symptoms, decreased work ability and the deterioration in quality of life for several weeks and even months after the onset of the disease is increasing. The aim of the literature review is to search and study the existing literature data regarding the lung impairment features in COVID-19, as well as the morphological and pathophysiological prerequisites for the long-term respiratory disorders in patients who have had this disease. The most common complaints of patients after acute COVID-19 are fatigue, dyspnea, cough and chest discomfort. In these cases restrictive pattern in the pulmonary function test, a reduced gas transfer and persistent changes in computed tomography often in the form of fibrosis are observed, less often in the form of bullous-emphysematous changes, bronchiectasis and pleural effusion. The main pathophysiological mechanisms of acute lung impairment in COVID-19 are direct viral toxicity, impaired function of the immune system, hyperinflammatory response, endotheliopathy, microcirculatory disorders and increased blood clotting with small and large vessels thrombosis, which can lead to pneumonia or acute respiratory distress syndrome. After the acute phase of COVID-19 the pathology of the lung can be caused by an immunogenic and hyperinflammatory response, hypercoagulability and lead to pulmonary fibrosis. The possible mechanisms of the pulmonary fibrosis are thrombotic processes, hemosiderosis, necrotic capillaritis, angiogenesis, hypoxia, cytokine storm. Thus abnormal immune response, hyperinflammation, endothelial dysfunction and excessive coagulation not only cause pneumonia or acute respiratory distress syndrome in acute COVID-19, but also may persist for a long time and contribute to pulmonary fibrosis in some patients. The causes of a longer duration and increased severity of the lung impairment in some people compared to others are the subject of current investigations.

Obesity and metabolic syndrome are one of the major public health problems in the 21st century due to their prevalence. Nonalcoholic fatty liver disease, dyslipidemia, type 2 diabetes mellitus, arterial hypertension, chronic inflammation and anemia are non-communicable diseases accompanying obesity. With obesity, there is a violation of iron metabolism, iron deficiency, which further contributes to the development of metabolic disorders. Iron is the second most abundant metal on Earth, and its bioavailability is reduced due to the formation of insoluble oxides, while iron deficiency is the most common nutritional disorder. Iron metabolism in the body is associated with the formation of reactive oxygen species involved in lipid peroxidation processes. Iron metabolism in the human body is regulated at all levels; dysregulation of any stage of metabolism can lead to iron deficiency and the development of anemia associated with obesity. This review article summarizes data on molecular and cellular abnormalities in iron metabolism in obesity and metabolic syndrome. The aim of our study was to study, according to the literature, pathophysiological disorders in iron metabolism in the development of obesity and metabolic syndrome. In the future, more research is required to study iron metabolism in obesity with the aim of their preventive and therapeutic effects. The role of oxidative stress in impaired iron metabolism in obesity has not been fully studied, while iron deficiency enhances lipid peroxidation processes in antioxidant deficiency. Under these conditions, oxidative stress can damage cells and destroy red blood cells. The question arises whether the restoration of iron homeostasis in obesity can improve metabolic, inflammatory disorders and reduce the manifestation of oxidative stress, becoming a new innovative approach to the treatment of concomitant metabolic diseases associated with obesity.

Abstract Parkinson’s disease (PD) is a disabling neurodegenerative disorder in which multiple cell types, including dopaminergic and cholinergic neurons, are affected. The mechanisms of neurodegeneration in PD are not fully understood, limiting the development of therapies directed at disease-relevant molecular targets. C. elegans is a genetically tractable model system that can be used to disentangle disease mechanisms in complex diseases such as PD. Such mechanisms can be studied combining high-throughput molecular profiling technologies such as transcriptomics and metabolomics. However, the integrative analysis of multi-omics data in order to unravel disease mechanisms is a challenging task without advanced bioinformatics training. Galaxy, a widely-used resource for enabling bioinformatics analysis by the broad scientific community, has poor representation of multi-omics integration pipelines. We present the integrative analysis of gene expression and metabolite levels of a C. elegans PD model using GAIT-GM, a new Galaxy tool for multi-omics data analysis. Using GAIT-GM, we discovered an association between branched-chain amino acid metabolism and cholinergic neurons in the C. elegans PD model. An independent follow-up experiment uncovered cholinergic neurodegeneration in the C. elegans model that is consistent with cholinergic cell loss observed in PD. GAIT-GM is an easy to use Galaxy-based tool for generating novel testable hypotheses of disease mechanisms involving gene-metabolite relationships.

Abstract Human exome sequencing is a classical method used in most medical genetic applications. The leaders in the field are the manufacturers of enrichment kits based on hybridization of cRNA or cDNA biotinylated probes specific for a genomic region of interest. Recently, the platforms manufactured by the Chinese company MGI Tech have become widespread in Europe and Asia. The reliability and quality of the obtained data are already beyond any doubt. However, only a few kits compatible with these sequencers can be used for such specific tasks as exome sequencing. We developed our own solution for library pre-capture pooling and exome enrichment with Agilent probes. In this work, using a set of the standard benchmark samples from the Platinum Genome collection, we demonstrate that the qualitative and quantitative parameters of our protocol which we called “RSMU_exome” exceed those of the MGI Tech kit. Our protocol allows for identifying more SNV and indels, generates fewer PCR duplicates, enables pooling of more samples in a single enrichment procedure, and requires less raw data to obtain results comparable with the MGI Tech's protocol. The cost of our protocol is also lower than that of MGI Tech's solution.

Background. The problem of gastric cancer remains unresolved throughout the world, while chronic atrophic gastritis (CAG) increases the likelihood of its development by 15 times. In the Russian Federation, the incidence of gastric cancer (GC) is among the highest, with it prevailing among males. One of the leading mechanisms in molecular pathology of membranes is lipid peroxidation (LPO). The severity of oxidative membrane damage depends on concomitant diseases, contributing to emergence and progression of pathological processes and development of cancer. Currently, the problem of LPO is unsolved in biological systems.The aim of this study was to investigate the state of LPO and antioxidant defense system in CAG and GC. Materials and methods. The parameters were studied in 45 patients with CAG and 50 patients with GC. The control group included 50 practically healthy volunteers without gastrointestinal complaints, who did not have changes in the gastric mucosa according to the fibroesophagogastroduodenoscopy (FEGDS) findings.Results. In patients with CAG, an increase in malondialdehyde, superoxide dismutase, catalase, glutathione S-transferase, and glutathione peroxidase was found in the blood plasma compared with the control group. In patients with CAG, lipid peroxidation was activated, and the malondialdehyde level increased by 3.5 times relative to normal values. At the same time, the body fought against oxidative stress by increasing the activity of antioxidant enzymes, such as superoxide dismutase, catalase, glutathione S-transferase, and glutathione peroxidase. All patients with GC showed pronounced oxidative stress in the blood plasma in the form of a 45-fold increase in malondialdehyde. The activity of the main antioxidant enzyme superoxide dismutase was reduced in GC. Catalase was activated, which indicated pronounced oxidative stress, significant damage to blood vessels, and massive cell death. Glutathione-related enzymes (glutathione S-transferase and glutathione peroxidase) and the antioxidant protein ceruloplasmin were activated, which also indicated significant oxidative stress and severe intoxication in patients with GC.Conclusion. Depending on the stage and type of cancer, an in-depth study of lipid peroxidation and factors of the antioxidant defense system can be used to correct therapy and prevent cancer and can serve as markers of progression and prognosis in gastric cancer.

Non-alcoholic fatty liver disease (NAFLD) is the leading cause of liver disease in highly developed countries. The risk of developing NAFLD and associated complications varies greatly among people of different nationalities and is determined by environmental and genetic factors. Genome-wide studies have revealed strong and reproducible associations between gene variations such as PNPLA3, TM6SF2, MBOAT7, GCKR, HSD17B1, and NAFLD. In this article, we consider the influence of genes and environmental factors on the pathophysiological features of NAFLD. The use of a sufficient population sample with the analysis of SNP arrays and the use of sequencing methods (exome and genome as a whole) will lead to the discovery of additional genetic variants, will inevitably improve the understanding of the pathogenesis of NAFLD, and will allow the development of a technology for personalized risk in assessing the disease in a patient. The aim of our study was to study the genetic predictors of NAFLD based on literature data with the interpretation of the studies. There is now strong evidence that specific variants of genetic risk have a large effect on NAFLD, and their effect is comparable to that of major metabolic risk factors such as obesity and type 2 diabetes. The increased risk extends to the onset and progression of the entire spectrum of NAFLD manifestations, including overall mortality due to liver disease. Currently, individual genetic variants do not allow the creation of a personalized risk profile; therefore, the most expedient approach today is the development of polygenic risk assessments. The number of genetic loci associated with the prevalence and outcome of NAFLD remains limited. The use of a sufficient population sample with the analysis of SNP arrays and the use of sequencing methods (exome and genome as a whole) will lead to the discovery of additional genetic variants and will inevitably improve the understanding of the pathogenesis of NAFLD and will allow the development of a technology for personalized risk in the assessment of the disease.

The aim: to compare the efficacy and tolerability of the leukotriene modifier and inhaled corticosteroids in combination with long-acting β2-agonist formoterol in steroid-naive patients with asthma combined with COPD with neutrophilic inflammation. Materials and methods. After obtaining the written consent, 30 patients with asthma combined with COPD and a number of blood neutrophils >4000/μl were randomized (1:1): group I – received a fixed combination of budesonide/formoterol 160/4.5 μg/1 inhalation twice daily as a basic therapy; group II – montelukast 1 tab. (10 mg) once daily and inhalation of formoterol 12 mcg/dose twice daily. The duration of therapy was 12 weeks. General clinical methods, asthma control questionnaires, COPD questionnaire, physical tolerance evaluation (6-minute walk test), pulmonary function tests, quality of life assessment were performed to all the patients before and after the treatment course studied. Results. The combination of budesonide/formoterol improved clinical symptoms – significantly (P

Tumor molecular profiling in patients with non-small cell lung cancer (NSCLC) is used to identify driver mutations, which lead to premature carcinogenesis in more than 80% of adenocarcinoma cases, including epidermal growth factor receptor (EGFR) mutations. Identification of specific somatic aberrations allows to personalize treatment. Personalization of treatment resulted in improvement of NSCLC outcomes. The aim of our study was to consider scientific data on modern concepts of treatment of patients with non-small cell lung cancer with previously detected oncogenic mutations, especially EGFR mutation. In our study we analyzed scientific papers and data of international scientific literature on the problem of lung cancer treatment. Methods used: scientific research, analytical and generalizing. Different drugs are used in treatment of lung cancer. Choice of treatment scheme depends on type and presence of mutations. Patients with advanced non-small-cell lung cancer and detected mutation in the EGFR can be treated with tyrosine kinase inhibitors (TKIs). Nowadays three first generation drugs are recommended by FDA: afatinib, erlotinib, gefitinib. They showed good clinical benefit. Most patients with metastatic NSCLC typically show disease progression after approximately 9 to 13 months of erlotinib, gefitinib, or afatinib therapy. The first and only commercially available third-generation EGFR TKI is оsimertinib - an oral drug, which selectively inhibits both EGFR-TKI and EGFR T790M resistance mutations. Nowadays scientists are in active investigation of mechanisms of acquired resistance to TKIs, but little is known yet. Clinical success can be observed in patients who were treated with TKIs. EGFR T790M is a mutation that leads to acquired resistance to EGFR TKI therapy. Its incidence is approximately 60% after disease progression on TKI drugs (erlotinib, gefitinib, or aphatinib). Third-generation EGFR TKIs demonstrate high efficacy, but acquired resistance development cannot be avoided. Mechanisms of acquired resistance to these agents are still investigated.

Background. Prostate cancer is one of the most common male malignancies worldwide that ranks second in cancer-related mortality. Artificial intelligence can reduce subjectivity and improve the efficiency of prostate cancer diagnosis using fewer resources as compared to standard diagnostic scheme. This review aims to highlight the main concepts of prostate cancer diagnosis and artificial intelligence application and to determine achievements, current trends, and potential research directions in this field, using bibliometric analysis. Materials and Methods.The studies on the application of artificial intelligence in the morphological diagnosis of prostate cancer for the past 35 years were searched for in the Scopus database using “artificial intelligence” and “prostate cancer” keywords. The selected studies were systematized using Scopus bibliometric tools and the VOSviewer software. Results. The number of publications in this research field has drastically increased since 2016, with most research carried out in the United States, Canada, and the United Kingdom. They can be divided into three thematic clusters and three qualitative stages in the development of this research field in timeline aspect. Conclusions. Artificial intelligence algorithms are now being actively developed, playing a huge role in the diagnosis of prostate cancer. Further development and improvement of artificial intelligence algorithms have the potential to automate and standardize the diagnosis of prostate cancer.

Abstract This study aimed to determine possible association of eight polymorphisms of seven MMP genes with essential hypertension (EH) in a Caucasian population of Central Russia. Eight SNPs of the MMP1, MMP2, MMP3, MMP7, MMP8, MMP9, and MMP12 genes and their gene–gene (epistatic) interactions were analyzed for association with EH in a cohort of 939 patients and 466 controls using logistic regression and assuming additive, recessive, and dominant genetic models. The functional significance of the polymorphisms associated with EH and 114 variants linked to them (r2 ≥ 0.8) was analyzed in silico. Allele G of rs11568818 MMP7 was associated with EH according to all three genetic models (OR = 0.58–0.70, pperm = 0.01–0.03). The above eight SNPs were associated with the disorder within 12 most significant epistatic models (OR = 1.49–1.93, pperm

Introduction. The increase in the number of respiratory lesions in the context of the COVID-19 pandemic and the tuberculosis epidemic leads to many complications, including calcification or pathological lung biomineralization (PBL). Respiratory remodeling caused by fibrosis and concomitant calcification is an important pathogen in chronic obstructive pulmonary disease (COPD) and subsequent chronic respiratory failure. The work aims to conduct bibliometric analysis and generalization of data from scientific sources to study the role of pathological biomineralization of lung tissue. Materials and methods. The authors searched for information in electronic databases such as PubMed, Scopus, Web of Science, and Google Scholar, in the key terms «pathological lung biomineralization» «lung calcification.» For bibliometric analysis, an online platform for monitoring and analysis of international research using visualization tools and modern citation metrics SciVal (Scopus) and a tool for building and visualizing bibliometric networks VOSviewer were used. Results. Pathological mineralization of the lungs is a multifactorial phenomenon: hypercalcemia, change of acid-base state in the alkaline direction, damage to lung tissue by infectious agents, genetic heredity. The danger of pathological biomineralization of the lungs is the gradual invisible occurrence of respiratory failure. We conducted a bibliometric analysis of the scientific literature. The number of publications on PBL has increased significantly over the past 10 years. Scientists from the United States, Japan, China, and India occupy the leading positions in this area. Analysis of publishing activity using the VOSviewer bibliometric network visualization tool for 1946-2022 by keywords showed the presence of 4 chronological publication stages. Among the 1356 publications analyzed, the most relevant areas of publishing activity are works on PBL in malignant neoplasms and tuberculosis, current radiological diagnosis of PBL, an association of PBL with inflammation and osteoporosis, biomarkers and biomaterials associated with PBL

Today, breast cancer occupies a leading position in the structure of morbidity and mortality among women in Ukraineand and throughout the world. Late diagnosis of the disease adversely affects the prognosis. Since this pathology is characterized by a wide range of gene mutations, the relationship between the molecular genetic characteristics of a tumor and the prognostic and clinical characteristics of breast cancer is an extremely important issue. The PI3K/Akt signaling cascade is one of the key intracellular signaling pathways associated with the control of cell proliferation and regulation of potential oncogene protein kinase B/Akt functions. It can suppress apoptosis in different types of cancer, contributing to tumor cells survival. Also, mutations and amplification of the PI3K/Akt cascade components cause malignant cell transformation of various origin. The PIK3CA gene is one of the oncogenes, somatic mutations in which play an important role in the pathogenesis and progression of breast cancer. It encodes p110-α, the catalytic subunit of phosphatidylinositol-3-kinase-α. The most frequent mutation in PIK3CA gene is H1047R. Conclusions. Numerous studies have shown that PIK3CA gene mutations in breast cancer patients have the potential to become a clinically important biomarker for improving the disease diagnosis and developing individualized targeted therapy. In this literature review we discuss the molecular mechanisms of PI3K signaling cascade activation and the role of PIK3CA mutations in the development of breast cancer.

BackgroundCutaneous leishmaniasis (CL) is a vector-borne parasitic diseases of public health importance that is prevalent in the West Bank but not in the Gaza Strip. The disease caused by parasitic protozoans from the genus Leishmania and it is transmitted by infected phlebotomine sand flies. The aim of our study is to investigate the eco-epidemiological parameters and spatiotemporal projections of CL in Palestine over a 30-years period from 1990 through 2020 and to explore future projections until 2060.Methodology/principal findingsThis long-term descriptive epidemiological study includes investigation of demographic characteristics of reported patients by the Palestinian Ministry of Health (PMoH). Moreover, we explored spatiotemporal distribution of CL including future projection based on climate change scenarios. The number of CL patients reported during this period was 5855 cases, and the average annual incidence rate (AAIR) was 18.5 cases/105 population. The male to female ratio was 1.25:1. Patients-age ranged from 2 months to 89 years (mean = 22.5, std 18.67, and the median was 18 years). More than 65% of the cases came from three governates in the West Bank; Jenin 29% (1617 cases), Jericho 25% (1403), and Tubas 12% (658) with no cases reported in the Gaza Strip. Seasonal occurrence of CL starts to increase in December and peaked during March and April of the following year. Current distribution of CL indicate that Jericho, Tubas, Jenin and Nablus have the most suitable climatic settings for the sandfly vectors. Future projections until 2060 suggest an increasing incidence from northwest of Jenin down to the southwest of Ramallah, disappearance of the foci in Jericho and Tubas throughout the Jordan Vally, and possible emergence of new foci in Gaza Strip.Conclusions/significanceThe future projection of CL in Palestine until 2060 show a tendency of increasing incidence in the north western parts of the West Bank, disappearance from Jericho and Tubas throughout the Jordan Vally, and emergence of new CL endemic foci in the Gaza Strip. These results should be considered to implement effective control and surveillance systems to counteract spatial expansion of CL vectors.

The aim of the study was to analyze the state of the reaction of the hemostasis system in rats to a single and multiple exposures to hypoxic hypoxia of strong intensity. Material and methods. Male rats (40 individuals) of the Wistar line were used in the work. Animals have been subjected to a single / daily multiple hypoxic hypoxia by chamber ascent for 1 hour. Hypoxic hypoxia was modeled with the input-outlet chamber. The air discharge created in the pressure chamber in the training mode corresponded to the liftoff to the «height» of 7000 m above sea level (41.105 kPa, 308.3 mm Hg, hypoxia of strong intensity). Results and discussion. A single exposure to the strong intensity of hypoxic hypoxia is characterized by the state of thrombotic readiness (based on the revealed hypercoagulation and high level of markers of intravascular coagulation). The shortening of clot formation start time, increase in the α angle and the maximum bunch density were revealed according to the thromboelastography data. The activation of hemostasis system thrombocytic part, hypercoagulation through the internal clotting path with the thrombinemia signs disappearance have been revealed after completion of the 30-day cycle of severe intensity hypoxia. In addition, the increase in the blood plasma antithrombin reserve was found in the group of experimental animals. The lengthening of clot formation time was recorded by the thromboelastogram results.

In 2018, 3,539 new cases of malignant ovarian neoplasms and 1,808 related deaths were registered in Ukraine. The one-year survival rate for ovarian cancer patients is 65 %, while the three-year and five-year survival rates are 40 % and 32 %, respectively. The aim of the work is to analyze the scientific literature to estimate the prevalence, mechanisms of development and diagnostic value of pathological biomineralization (PBM) in ovarian tumors. Calcification is one of the clinical features of ovarian cancer. Approximately 8% of cases are diagnosed by computed tomography. PBM in ovarian tumors can be divided into 2 groups: calcification of the tumor parenchyma, capsule or stroma and biomineralization as psammoma bodies (PB). Calcification of the ovarian cancer parenchyma is a secondary change in tumor tissue due to the secretion of collagen and direct effect of hormones. Nevertheless, the PBM development in the ovarian capsule, stroma or PB is one of the possible protective responses of tissues to the tumor spread and invasive growth. The presence of PT is a reliable pathognomonic sign of malignant ovarian tumors and can be identified both by instrumental diagnostic tests (ultrasound, CT and MRI) and histology. Also, the presence of biominerals contributes to an increase of five-year survival rates for patients with ovarian tumors up to 50%. The study of the chemical composition of calcifications of serous ovarian tumors by various methods showed the presence of inorganic elements such as aluminum (Al), cadmium (Cd), potassium (K), cobalt (Co), chromium (Cr), iron (Fe), zinc (Zn) and copper (Cu), magnesium (Mg) and sodium (Na). It was found that Calcium (Ca) and phosphorus (P) formed the biomineral basis of ovarian tumor calcifications. It has also been found that biomarkers of mineralization such as BMP-2, OPN, Runx2 and Osterix were also involved in pathological calcification in serous ovarian carcinomas. It was shown that ovarian tumors PBM development involves a few different mechanisms. It may indicate a link between the tumor stage and the diagnostic value of calcifications in ovarian tumors, as well as the subsequent prognosis of this disease. There is also a variation in the prevalence of calcification in different histological types of ovarian tumors. PBM is detected predominantly in the serous ovarian adenocarcinoma. However, for serous adenocarcinoma with a large number of PB, a separate nosology, “Psammocarcinoma”, was identified. It is obvious that the small calcifications (less than 200 μm) are not detected by radiology. That is why their detection occurs most often with histology. However, there is a lack of information on the prevalence of PBM in ovarian tumors, which would be based on a detailed histological and histochemical study.

Implementation of anti -D prophylaxis significantly reduced the degree of allogenic immunization (AI), while this method of prevention is not universal. According to the data of different authors, about 0.3% of Rh (D) - negative women still become Rh (D) AI. We failed to find data as to the state of cellular immunity (CI) in rhesus-sensitized (Rh-S) pregnancy, as well as the possibility of its indicators use for predicting and diagnosing the pregnancy course in the group of women under study. The objective: to evaluate the state of CI and identify its most diagnostic important components in the cohort of rhesus-sensitized women. Materials and methods. The state of CI (population and subpopulation of lymphocytes) was studied in 82 pregnant women, 37 had Rh-S with different titers of antibodies, control group comprised 45 healthy women without rhesus sensitization. Results: The most significant indicators of Rh-S women's CI were distributed among the three main factorial components. Multivariate analysis method was used. Activated subpopulations of T-lymphocytes and T-killers comprised Factor 1. Factor 2 is represented by indices of the lymphocyte population - B-lymphocytes (CD19 +) with a direct correlation of 0.88, as well as T-lymphocytes (CD3 +) with an inverse - 0.92. Factor 3 included the main subpopulations of lymphocytes (T-helpers and T- suppressors), as well as the immunoregulatory index (the coefficient of their ratio). Conclusion. The most significant indicators for CI study in Rh-S women are: CD19 + (B-lymphocytes), CD3 + (T-lymphocytes), CD3 + HLA-DR + (activated T - lymphocytes), CD3 + CD4 + HLA-DR + ( activated T -helpers), CD3 + CD8 + HLA-DR + (activated T-suppressors), NK-cells CD3-CD16 / 56 + (T-killers) and immunoregulatory index CD3 + CD4 + / CD3 + CD8 +.

The immunological and biochemical changes caused by pregnancy may uncover new aspects of immune tolerance, applicable in physiological and pathological contexts, and show up new therapeutic strategies for improving pregnancy outcomes. Isoimmune conflict in pregnancy is primarily related to the risk of pre-natal fetal death caused by massive hemolysis when incompatible with Rh and / or AB0 antigens. The objective: The objective: to evaluate the role of redox homeostasis in the formation of the immune response in isoimmune conflict during pregnancy. Results. The results obtained indicate the activation of T- and B-lymphocytes, which may be explained by the activation of cytokines IL-1, IL-6, IL-10. In pregnancy isoimmune conflict moderate metabolic acidosis is observed with a predominance of the lactic acid component and the depletion of buffer reserves. Conclusions. Isoimmune conflict leads to moderate formation of oxidative stress, that can be described as violation of redox-homeostasis, which in turn can be a consequence of cytotoxic reactions.

The objective: to study the efficacy of probiotic and vitamin D use in prophylaxis of infectious diseases in premature infants. Materials and methods. The reseach has been conducted on the base of theOdessaNationalMedicalUniversity– neonatal unit of the maternity hospital N 7 (Odessa). The I group consisted of 20 premature infants (PI) who got BioGiy drops. The II group conssted of 19 PI, who got BioGiy drops and vitamin D3. Control group- 23 PI who did not get the preparations mentioned above. At birth and at the age of 3-4 months complex immunological investigation was carried out. Every month the morbidity of PI was observed. Results. PI are more likely to suffer from infectious diseases, functional disorders of the gastrointestinal tract and hypovitaminosis D. The results obtained indicate a high effectiveness of probiotic with vitamin D3 use for the prevention of infectious diseases in PI. The greatest effect was observed in the prevention of skin infections and respiratory diseases of the upper respiratory tract as a reduction of respiratory episodes frequency, acceleration of recovery and lighter course of the disease. Also, the combination of probiotic and vitamin D has proven itself as a means of preventing hypovitaminosis D in PI.

Premature birth (PB) is the most important aspects in maternal and child health care. The frequency of PB and birth of immature infants is increasing and ranges from 4.0 to 15.0-20.0%. In Ukraineits frequency varies from 3.0% to 12.0%. Preterm infants account for 60-70% of early neonatal and 65-75% of infant mortality. The aim: to examine the main premature baby’s immune system indexes as it is the immune system state that determines survival of a newborn child, the peculiarity of its life in neonatal period, effectiveness of therapeutic and rehabilitation measures, as well as the degree of disability. There were two groups of premature children under study: the I group, n = 62 premature infants, the age of gestation 34-36 weeks without perinatal pathology. The IId group (control ) was represented by 15 healthy newborns, aged 38-40 weeks of gestation. The study was carried out in the first 3 days of the child's life by flow cytofluorometry. In premature infants, the immaturity of the immune system was noted in the form of decrease in all indices of nonspecific immunity: the level of the complement component of C3, the level of immunoglobulins class A, G and M and the values of T-killers and B-lymphocytes.

Aryaev N. L., Marichereda V. G., Shevchenko I. M., Moskalenko T. Ya., El Mezevgi H. M., Shevchenko N. V. Оценка взаимосвязи факторов риска преждевременных родов в различные сроки беременности = Assess of preterm birth risk factors relationship at various pregnancy stages. Journal of Education, Health and Sport. 2016;6(9):422-432. eISSN 2391-8306. DOI http://dx.doi.org/10.5281/zenodo.153862 http://ojs.ukw.edu.pl/index.php/johs/article/view/3850 The journal has had 7 points in Ministry of Science and Higher Education parametric evaluation. Part B item 755 (23.12.2015). 755 Journal of Education, Health and Sport eISSN 2391-8306 7 © The Author (s) 2016; This article is published with open access at Licensee Open Journal Systems of Kazimierz Wielki University in Bydgoszcz, Poland Open Access. This article is distributed under the terms of the Creative Commons Attribution Noncommercial License which permits any noncommercial use, distribution, and reproduction in any medium, provided the original author(s) and source are credited. This is an open access article licensed under the terms of the Creative Commons Attribution Non Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted, non commercial use, distribution and reproduction in any medium, provided the work is properly cited. This is an open access article licensed under the terms of the Creative Commons Attribution Non Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted, non commercial use, distribution and reproduction in any medium, provided the work is properly cited. The authors declare that there is no conflict of interests regarding the publication of this paper. Received: 05.08.2016. Revised 25.08.2016. Accepted: 06.09.2016. УДК 618.396 /616-021.1 ОЦЕНКА ВЗАИМОСВЯЗИ ФАКТОРОВ РИСКА ПРЕЖДЕВРЕМЕННЫХ РОДОВ В РАЗЛИЧНЫЕ СРОКИ БЕРЕМЕННОСТИ Н. Л. Аряев1, В. Г. Маричереда1, И. М. Шевченко1, Т. Я. Москаленко1,2, Х. М. Эль-Мезевги1, Н. В. Шевченко2 1Одесский национальный медицинский университет, г. Одесса, Украина 2Родильный дом №7, г. Одесса, Украина Реферат В результате проведения ретроспективного анализа медицинской документации отмечено, что наиболее частыми и статистически значимыми факторами, сопровождающими и обусловливающими преждевременные роды, являются маточные кровотечения, ИЦН, инфекции различной этиологии и локализации, дисфункция плаценты, наличие выкидышей и преждевременных родов в анамнезе, низкий индекс массы тела, гинекологические операции в анамнезе и возраст матери старше 35 лет. В иерархии рисков ПР в сроке до 33 недель первое место занимают маточные кровотечения, затем следуют инфекции различной этиологии и локализации и ИЦН. При ПР в сроке 33-37 недель чаще фиксируется ИЦН, затем следуют маточные кровотечения и дисфункция плаценты. Наличие инфекционного процесса у беременной может привести к ПР в сроке до 33 недель, маточные кровотечения свидетельствуют о возможности наступления ПР до 33 недель. При наличии ИЦН у беременной наступление ПР в 33-37 недель возможно с вероятностью и достоверностью в 71,58%, при дисфункции плаценты вероятность и достоверность равна 62,76%. Маточные кровотечения свидетельствуют о возможности ПР с вероятностью и достоверностью в 57,13%, инфекционный процесс может провоцировать наступление ПР с вероятностью и достоверностью в 52,25%. Ключевые слова: преждевременные роды, факторы риска. ASSESS OF PRETERM BIRTH RISK FACTORS RELATIONSHIP AT VARIOUS PREGNANCY STAGES N. L. Aryaev1, V. G. Marichereda1, I. M. Shevchenko1, T. Ya. Moskalenko1,2, H. M. El Mezevgi1, N. V. Shevchenko2 1Odessa National Medical University, Odessa, Ukraine 2Maternity Hospital №7, Odessa, Ukraine Summary The result of the retrospective analysis of medical records indicated that the most frequent and statistically significant factors that accompany and cause premature labor are uterine bleeding, cervical incompetence, infections of different etiology and localization, dysfunction of placenta, presence of miscarriages and premature births in history, low body mass index, gynecological surgery and history of maternal age older than 35 years. Uterine bleedings rank first in the risk hierarchy of premature births (PB) at the terms up to 33 weeks, and they followed by infection of various etiology and localization and cervical incompetence. When the PR are in 33-37 weeks, cervical incompetence, followed by uterine bleeding and dysfunction of placenta are usually fixed. Infection in a pregnant woman can lead to PR in the period up to 33 weeks, as well as uterine bleeding suggests the possibility of occurrence of PR at the same term. Presence of cervical incompetence in pregnant may result in PB at the terms of 33-37 weeks, with probability and accuracy to 71.58%, while placental dysfunction’s accuracy is 62.76%. Uterine bleeding suggests the possibility of PB with probability and accuracy to 57.13%, infectious can provoke the onset of PB with probability and accuracy to 52.25%. Key words: prematurity, risk factors.

Nagornaya V. F., Moskalenko T. Ya., Gritsenko A. A. Descriptiveness of vaginal secretions pH in the vaginal microbiota assessment in pregnant women. Journal of Education, Health and Sport. 2016;6(7):67-74. eISSN 2391-8306. DOI http://dx.doi.org/10.5281/zenodo.57113 http://ojs.ukw.edu.pl/index.php/johs/article/view/3659 The journal has had 7 points in Ministry of Science and Higher Education parametric evaluation. Part B item 755 (23.12.2015). 755 Journal of Education, Health and Sport eISSN 2391-8306 7 © The Author (s) 2016; This article is published with open access at Licensee Open Journal Systems of Kazimierz Wielki University in Bydgoszcz, Poland Open Access. This article is distributed under the terms of the Creative Commons Attribution Noncommercial License which permits any noncommercial use, distribution, and reproduction in any medium, provided the original author(s) and source are credited. This is an open access article licensed under the terms of the Creative Commons Attribution Non Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted, non commercial use, distribution and reproduction in any medium, provided the work is properly cited. This is an open access article licensed under the terms of the Creative Commons Attribution Non Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted, non commercial use, distribution and reproduction in any medium, provided the work is properly cited. The authors declare that there is no conflict of interests regarding the publication of this paper. Received: 25.05.2016. Revised 25.06.2016. Accepted: 28.06.2016. UDC 618.3-06: 618.15-022.7] -07-085 DESCRIPTIVENESS OF VAGINAL SECRETIONS pH IN THE VAGINAL MICROBIOTA ASSESSMENT IN PREGNANT WOMEN V. F. Nagornaya1, T. Ya. Moskalenko1, 2, A. A. Gritsenko2 1Odessa National Medical University, Department of Obstetrics and Gynecology №1; 2 KU maternity hospital №7, Odessa Summary 143 pregnant and 20 non-pregnant women have been examined. The objective: to determine the information content of the vaginal fluid pH. Methods used: Cytological, standard microbiological, real time PCR, the measurement of vaginal fluid pH. Results: five types of vaginal microbiota have been revealed, as well as a clear link of pH and the quantitative characteristic of microflora, high inverse correlation with estradiol content was shown, and correspondence to the number of gestation complications and the number of inflammatory diseases of the somatic plan was proved. The authors recommend to use pH of the vaginal fluid as an indicator of the state of vaginal biotope in the course of pregnancy. Keywords: pH of the vaginal secretion, vaginal biotope pregnancy.

Aim. To study distribution of some karyotype variants among patients of different age with acute myeloid leukemia (AML). Material and methods. Distribution of balanced, normal, unbalanced, complex and monosomic karyotype among 244 patients with de novo AML in age groups 16-20, 21-30, 31-40, 41-50, 51-60, 61 and older was analysed. Results. There is difference in frequency of balanced and complex karyotype in patients under and over 60 years. Number of AML patients with balanced aberrations including favourable variants t(8;21), t(15;17) and inv(16) falls after 60 years of age (6.7% versus 15.0% in patients aged 16-20 years; p < 0.001), while a complex karyotype occurs more frequently in AML patients at the age of 61 and older (56.8% versus 2.7% in the group 16-20 years; p < 0.001). With age, more frequently detected is the most unfavourable monosomic karyotype with aberrations similar to those in myelodysplastic syndrome (57.1% in patients aged 16-60 years and in 80.0% in the group of 61 years of age and over). Conclusion. Age-specific karyotype features detected may be explained by different biological mechanisms involved in leukosogenesis in young and elderly AML patients.

Aim. To estimate the extent of FLT3 and NPM1 gene mutations and the impact of mutations of FLT3-ITD on the survival of patients with acute myeloid leukemias (AML). Materials and methods. The nucleus-containing cells of bone marrow and blood were studied in 43 patients with AML. Polymerase chain reaction analysis of total genomic DNA was applied. Results. Mutations of FLT3-ITD, FLT3-TDK, and the NPM1 gene were found in 16 (37.2%) patients. A total of 19 mutations were revealed. There were 8 mutations of FLT3-ITD, 5 of FLT3-TKD, and 6 in the NPM1 gene. Single damages to genes were detected in 13 patients: FLT3-ITD in 6 (13.9%), FLT3-TKD in 4 (9.3%), and NPM1 in 3 (7%). Three (7%) patients exhibited 2 mutations simultaneously: in the NPM1 and FLT3-ITD in 2 (4.7%) and in the NPM1 gene and FLT3-TKD in 1 (2.3%). In AML patients with a normal karyotype and the FLT3-ITD-/NPM1- and FLT3-ITD+/ NPM1- genotypes, median overall survival was 17.3 versus 8 months (p = 0.069); and event-free survival (EFS) was 11 versus 5 months (p = 0.026). Univariate analysis established the negative impact of FLT3-ITD mutation on EFS. Conclusion. The findings allow AML patients with a normal karyotype and the FLT3-ITD-/NPM1- genotypes to be identified as a poor prognosis group.