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Based on the analysis of literary sources of PubMed, MedLine, The Cochrane Library, EMBASE database, the authors of the article give general provisions regarding post-translational modifications of histones (small proteins with a molecular weight of 10–15 kDa, which make up the largest part of nuclear proteins), which are associated with the development of metabolic dysfunction-associated fatty liver disease. The authors emphasize that post-translational histone modifications regulate the activity of gene expression, and each of these types differently changes the structure of chromatin and, as a result, gene expression. Currently, more than 20 types of histone protein modifications have been identified (acetylation, biotinylation, butyrylation, 2-hydroxybutyrylation, ADP-ribosylation, N-formylation, hydroxylation, glycosylation, glutarylation, dopaminylation, proline isomerization and aspartic acid carbonylation, crotonylation, lactylation, malonylation, methylation, propionylation, succinylation, SUMOylation, ubiquitination, phosphorylation, citrullination). Epigenetic and epitranscriptomic changes are induced by lifestyle, especially the nature of diet and physical activity, by the influence of exogenous and endogenous factors. Prolonged epigenetic changes that determine the expression of target genes can be accompanied by the development of metabolic disorders and the progression of metabolic dysfunction-associated fatty liver disease. Histone modification is carried out by site-specific enzymes: writers, which identify a marker, and erasers, which “erase” a marker. Post-translational histone modifications change the local physicochemical environment and, based on this, directly affect the structure of the nucleosome and chromatin. Also, post-translational modifications of the N- and C-terminal tails of histone proteins act as “docking sites” that recruit specific molecular readers. Readers of histone modifications can act both in the intranucleosomal space, modifying adjacent histone sites or recruiting transcription factors, transcription activators and repressors, and in the internucleosomal space. The authors also describe the pathophysiological significance of post-translational histone modifications in the development of metabolic dysfunction-associated fatty liver disease, the diagnostic value of epigenetic biomarkers, and the potential of pharmacological management of histone modifications to achieve inhibition of the activity of the pathological process.

The literature review deals with DNA methylation, a key epigenetic mechanism that controls the activity of gene transcription, plays a decisive role in the formation of genomic imprinting, gene silencing, X-chromosome inactivation, RNA splicing, DNA repair, cell differentiation and cell reprogramming, and also determines the occurrence and development of liver steatotic lesions and metabolic disorders. Methylation of DNA cytosine dinucleotide (CpG) can be represented in two types: de novo CpG methylation, which is carried out by 5mC DNA writers — DNA-(cytosine-5)-methyltransferase (DNMT) 3a and 3b, and suppor­ting DNA methylation, which is performed by DNMT1 during DNA replication. It has been found that the maintenance DNA methylation allows the preservation of the methylation pattern characteristic of progenitor cells in the cells of the new generation, and the DNA methylation of the gene body is associated with its increased expression. Active demethylation of 5mC is carried out by TET dioxygenases, including three enzymatic representatives: TET1, TET2 and TET3. It has been demonstrated that aberrant methylation of DNA nucleotides is directly related to the activity of lipid synthesis, the degree of oxidative stress, the development of liver steatosis, low-grade inflammation, insulin resistance, and the progression of liver fibrosis. The authors presented in detail the functions and features of DNA methyltransferases, erasers, and readers of 5mC sites; possible violations of the balance of activity of writers and erasers of 5mC DNA; DNA methylation landscape and patterns; clinical significance of DNA methylation signatures in metabolic dysfunction-associated fatty liver disease. Global hypomethylation of genome, at least 55 genes, is observed in patients with metabolic dysfunction-associated fatty liver disease. The authors emphasize that the use of DNA methylation signatures is a promising direction for early diagnosis and prognosis of the course of metabolic dysfunction-associated fatty liver disease, while the study of molecular components of DNA methylation mechanisms involved in the regulation of gene expression, the dependence of their activity on exposure to the exposome will allow to persona­lize and improve recommendations for lifestyle and diet modification in patients with metabolic dysfunction-associated fatty liver disease.

The literature review highlights the issue of genetic risk factors associated with the development of metabolic dysfunction-associated fatty liver disease. Human genetic examinations revealed 132 genes among which 32 loci are strongly associated with the pathogenesis of metabolic dysfunction-associated fatty liver disease. It has been found that the risk of developing metabolic dysfunction-associated fatty liver disease is carried by single-nucleotide variants of various genes whose products are involved in lipid and carbohydrate metabolism, maintenance of the redox state, the development of inflammation and fibrosis of liver tissue, which are components of metabolic dysfunction-associated fatty liver disease reactome. The authors presented a detailed list of genetic factors singling out those that influence the risk of metabolic dysfunction-associated fatty liver disease and directly metabolic dysfunction-associated steatohepatitis and liver fibrosis. Also, they emphasized that it is the single-nucleotide variants of the genes of protein 3 containing a patatin-like phospholipase domain, transmembrane 6 superfamily member 2, and 17b-hydroxysteroid dehydrogenase type 13 that are characte­rized by the highest degree of association with metabolic dysfunction-associated fatty liver disease (odds ratio > 1.6) compared to single-nucleotide variants of other genes identified by gene association studies. The combination of several polymorphisms increases the risk of development and severity of metabolic dysfunction-associated fatty liver disease. The additive steatogenic effect of protein 3 single-nucleotide gene variants containing a patatin-like phospholipase domain and transmembrane 6 superfamily member 2 is probably due to an increased expression of genes involved in de novo lipogenesis. The authors emphasize the need for genetic risk assessment of metabolic dysfunction-associated fatty liver disease, which should include molecular genetic testing at an early stage of examination.

The literature review deals with the problem of metabolic dysfunction-associated fatty liver disease that is poorly studied in pediatric gastroenterology. Until recently, primary hepatic steatosis not associated with alcohol intake was defined as non-alcoholic fatty liver disease. Given the unity of the pathogenetic mechanisms underlying primary steatosis, associated steatohepatitis, liver fibrosis with metabolic disorders, such as visceral obesity, insulin resistance, meta-inflammation of adipose tissue, it was proposed to change the terminology. The authors present data on modern nomenclature definitions, etiological factors, prevalence, criteria of metabolic disorders and meta-inflammation associated with this nosology and specific to childhood. Metabolic dysfunction-associated fatty liver disease and nonalcoholic fatty liver disease are characterized by the development of hepatosteatosis. However, a distinguishing feature of metabolic dysfunction-associated fatty liver disease is the presence of metabolic disorders in a patient. It is believed that the use of the term “metabolic dysfunction-associated fatty liver disease” in clinical practice allows doctors to make a diagnosis more reliably and more accurately modify the patient’s lifestyle. Much attention is paid to the description of the heterogeneity of metabolic dysfunction-associated fatty liver disease in clinical practice, and a concise list of therapeutic options for metabolic dysfunction-associated fatty liver disease in childhood is presented.

Background. Treatment of epileptic seizures in young children, especially with epileptic encephalopathies (EE), is a difficult task, which is impossible in modern conditions without the use of a personified (precision) therapy. The diagnostic algorithm for EE must include genetic examination by the next-generation sequencing, which makes it possible to prescribe targeted therapy depending on the genetic etiology of the disorder. The article presents the results of own research on the effectiveness and approaches to targeted therapy of genetic epileptic encephalopathies in young children. Materials and methods. Fifty-eight children aged 0–3 years with clinical manifestations of epileptic encephalopathies, onset of seizures in the first year of life and diagnosed genetic etiology were included in the study. Pathogenic variants in genes associated with the development of epileptic seizures were identified in all children using the next-generation sequencing. The study included assessment of neurological status, history collection, evaluation of semiology and seizure type, development and screening for autism spectrum disorders at the age of 18 and 24 months, video-electroencephalography during night sleep, magnetic resonance imaging of the brain, assessment of antiepileptic treatment received by the child. Results. Of 58 children with EE who were prescribed antie­pileptic drugs, 10 (17.2 %) received monotherapy, 40 patients (69 %) received combined therapy with two anticonvulsants, and 8 children (13.8 %) — combined therapy with three or more anticonvulsants. Levetiracetam (31 patients), valproic acid salt preparations (20 cases), topiramate (11 children) and vigabatrin (10 cases) were most used antiepileptic drugs. In all examined patients with EE, we used schemes of targeted (persona­lized) antiepileptic therapy focused on the genetic etiology of the disorder. In children with tuberous sclerosis caused by mutations in the TSC1 and TSC2 genes, vigabatrin (50–150 mg/kg per day) was included in the antiepileptic therapy and showed efficacy in 75.0 % (9/12) of children with infantile spasms. Corticosteroids (adrenocorticotropic hormone or prednisone) were additionally included in the treatment regimen and showed effectiveness in 66.7 % of cases (4/6). In children with mutations in SCN1A gene, combined therapy including valproic acid, topiramate and clobazam, or valproic acid with levetiracetam and corticosteroids was used, which showed effectiveness in reducing the frequency of seizures in 100 % of cases. Conclusions. Epileptic encephalopathies are a heterogeneous group of genetic disorders in young children that are difficult to treat and often have a malignant course. Since standard antiepileptic drugs are often insufficiently effective in epileptic encephalopathies, the use of targeted therapy drugs and alternative treatments such as hormone therapy are extremely important. The goal of treatment for epileptic encephalopathies is not only to control seizures, but also to prevent the development of neurological and cognitive deficits and restore lost functions.

Background. Breast milk (BM) is an optimal nutritional product for newborns and a source of exogenous microRNAs (miR). MiR-148a is one of the most highly expressed miR of BM. Currently, there is a lack of data on the miR-148a effect on the development of necrotizing enterocolitis (NEC) in premature newborns. The purpose of the study was to determine the influence of miR-148a of the mother’s BM on the risk of NEC development in preterm newborns. Materials and methods. We examined 74 newborns, who were treated in neonatal departments. We determined the level of miR-148a in the BM of 44 mothers of exclusively breastfed children. In parallel, we evaluated gene expression of the transcription factor T-bet in scrapings of the buccal mucosa of all the newborns. Three groups for comparison were selected: group 1 consisted of 32 newborns up to 37 weeks of gestation on breastfeeding (BF); group 2 — of 30 preterm newborns on artificial feeding; the control group — 12 full-term newborns on BF. Results. The gestational age median of group 1 children was 33 (31; 34) weeks; group 2 — 32.5 (32; 35) weeks; and it was comparatively higher in the control group (p 0.05). In group 2 compared to the first one, manifestations of NEC occurred significantly more often (p

The role of miRNA in the development of hepatobiliary diseases is considered in the scientific review. To write the article, information was searched using Scopus, Web of Science, MedLine, PubMed, Google Scholar, EMBASE, Global Health, The Cochrane Library databases. The authors provided information on the generation of a certain spectrum of miRNA by diffe­rent types of cells of the hepatobiliary system. The authors state that miR-122-5p, miR-101, miR-192, miR-193, miR-194, ­miR-802 are hepatocyte-associated microRNAs. It is known that nume­rous microRNAs are involved in the regulation of the inflammatory process: miR-21, miR-29a, miR-96, miR-122, miR-125b, ­miR-132, miR-155, miR-146a, miR-150, miR-155, miR-181 and let-7. Among the many microRNAs involved in the regulation of inflammation in the liver, miR-122 and miR-155 are the most stu­died. It is stated that microRNAs such as let-7d, miR-15b, ­miR-19b, ­miR-21, ­miR-24, miR-29c, miR-122, miR-145, ­miR-155, ­miR-199, miR-200c, miR-378a are the most important modulators for the activity of fibrosis development in various tissues of the body, including liver tissue. MicroRNAs involved in the development of TGF-β1-induced liver fibrosis are presented. Scientists believe that since microRNAs regulate the cell cycle, proliferation and apoptosis of cells, they are factors that significantly affect the development of hepatobiliary tumors. It is emphasized that changes in miRNA profile in liver tissue or blood serum have their diagnostic value. Modulations of microRNAs are shown, which are associated with specific diseases of the liver and biliary tract with a high degree of probability. Thus, various miRNAs play an important role in the development of hepatobiliary diseases. A certain spectrum of ­miRNAs is generated by different cell types and plays an important role in the maturation and functioning of the hepatobiliary system. MicroRNAs indirectly participate in the synthesis of proteins, differentiation of cells, tissues and play an important pathogenetic role in the development of hepatobiliary diseases. The most important feature of microRNAs is their high resistance to the action of enzymatic substances, which allows them to be used as diagnostic or prognostic biomarkers.

Background. A balanced supply of macro- and microelements to various organs and systems is a prerequisite for maintaining human health. Deficiency or excess of macro- and microelements in saliva can be associated with both inflammation and oxidative damage to the oral tissues. Provision of calcium in the human body significantly affects the state of salivary ionome. However, currently there are few studies on the effect of Ca and vitamin D on the state of salivary ionome in healthy children. Purpose: to study the effect of combined use of prophylactic doses of Ca and vitamin D on the concentration of macro- and microelements in saliva of young children. Materials and methods. Under our supervision, there were 36 clinically healthy young children who received Calcicare 2.5 ml 3 times a day for 2 months. The study of the content of macro- and microelements in urine was carried out by optical emission spectrometry with an inductively coupled plasma. Statistical analysis of the results was performed using the application package Statistica 6.1 on a personal computer based on Intel Pentium processor. Results. The study showed that the combined use of calcium carbonate and vitamin D significantly changes the concentration of some macro- and microelements in saliva of young children. The level of some trace elements in saliva before the start of therapy with Calcicare correlated with the frequency of acute respiratory infections. Thus, a higher incidence of acute respiratory infections was observed in children with reduced salivary excretion of Ca and S. Young children had a low concentration of Ca and Mg in saliva before the course of Calcicare therapy. Treatment with Calcicare led to an activation of the metabolism of these macronutrients in saliva of young children, which was characterized by an increase in the level of Ca from 29.5 ± 4.4 mg/l to 60.1 ± 6.8 mg/l (p < 0.01), Mg from 4.9 ± 0.6 mg/l to 9.3 ± 0.8 mg/l (p < 0.01), S from 336.3 ± 3.8 mg/l to 2501.6 ± 275.4 mg/l (p

Некротизуючий ентероколіт (НЕК) - тяжке гастроінтестинальне захворювання, що уражує переважно недоношених немовлят. Неспецифічність клінічної картини та високий відсоток ускладнень обумовлюють необхідність ранньої діагностики та профілактики захворювання. Мета - встановити зв’язок між рівнем експресії T-bet у клітинах букальної слизової оболонки, розвитком НЕК та способом вигодовування в недоношених новонароджених немовлят. Матеріали та методи. Обстежено 74 новонароджених, які проходили лікування в неонатальних відділеннях. Виділено три групи порівняння: 1-шу становили 32 дитини, народжені до 37 тижнів гестації, які перебували на грудному вигодовуванні (ГВ); 2-гу - 30 недоношених новонароджених на штучному вигодовуванні (ШВ); контрольну - 12 доношених новонароджених на ГВ. Визначено рівень експресії гена фактора транскрипції T-bet у клітинах зіскрібка букальної слизової оболонки новонароджених. Для статистичного аналізу розраховано нормалізовані рівні експресії T-bet у клітинах слизових оболонок немовлят 1 і 2-ї груп дослідження щодо групи контролю, де рівень експресії визначених факторів прийнято за 1 у.о. Результати. Медіана гестаційного віку дітей 1-ї групи становила 33 (31; 34) тижні; 2-ї групи - 32,5 (32; 35) тижня; порівняно вищою вона була в групі контролю (р

Background. Breast milk (BM) is an important source of microRNAs (miRs). MicroRNAs are highly resistant to gastrointestinal enzymes and are well absorbed in the intestine. MiR-155 is one of the most expressed miR of BM. Currently, the effect of miR-155 of BM on the health of preterm neonates has not been almost studied. The objective was to determine the effect of miR-155 of BM on the health of preterm neonates. Materials and methods. We examined 74 newborns, who were treated in neonatal departments. We determined the level of miR-155 in the BM of 44 mothers of exclusively breastfed children. In parallel, we evaluated gene expression of the transcription factor FOXP3 in buccal smears of all neonates. Three comparison groups were selected: group 1 consisted of 32 newborns of up to 37 weeks of gestation; group 2 — of 30 preterm newborns on artificial fee­ding; control group — of 12 full-term breastfed newborns. Results. The gestational age median in group 1 was 33 (31; 34) weeks; in group 2 — 32.5 (32; 35) weeks; it was higher in the control group (p < 0.001) — 40 (39; 41) weeks. Neonatal encephalopathy as the main diagnosis occurred more often among full-term newborns (p 0.05). In group 2 compared to group 1, manifestations of necrotizing enterocolitis were detected significantly more often (p < 0.05): 30.0 ± 8.4 % vs 9.4 ± 5.2 %. The results of evaluating the miR-155 expression level in the BM of mothers of group 1 children prove that the corresponding indicator in the control group was exceeded by an ave­rage of 6.2 (4.1; 9.2) times (p < 0.001). Analysis of FOXP3 levels in buccal smears showed that all preterm newborns had significantly lower FOXP3 levels than that of full-term neonates (< 0.001). However, the expression of this factor was the lowest in group 2 (< 0.001): 0.08 (0.04; 0.16) c.u. in group 2 vs 0.21 (0.14; 0.38) c.u. in group 1. We found a direct moderate correlation between the expression levels of miR-155 of the BM and the FOXP3 in the mucosal cells of breastfed preterm neonates: r = 0.442 (p = 0.014). A significant decrease was noted in the expression of FOXP3 in children with necrotizing enterocolitis (0.11 (0.04; 0.25) c.u.) compared to newborns without such pathology (0.22 (0.09; 0.91) c.u.) (p

The medical and social significance of the problem of asthma in childhood is extremely high. Global Initiative for Asthma (GINA) for the management of this disease has been known since 1993, based on the best information available to date. Global Initiative for Asthma has now been updated — the 2022 GINA revision. GINA 2022, in particular, considers the use of a single inhaler (inhaled glucocorticoid and formoterol) both to relieve symptoms and to provide basic therapy, emphasizes the importance of having a written plan of action for asthma. Today, children with asthma are thought to have a similar risk of contracting SARS-CoV-2 as children without asthma. In the context of a coronavirus pandemic, it is essential for asthma patients to continue their proper treatment with good control of clinical symptoms. A new aspect is that when COVID-19 is confirmed or suspected, the use of nebulizers should be avoided where possible due to the risk of transmitting the infection to other patients, family members and healthcare professio­nals. Although spirometry monitoring is indeed an important tool, in a pandemic it is recommended to limit it to patients in whom the results of this study may affect treatment. It is important to follow the recommendations of infection control, take precautions to reduce the risk of infection. Recent developments in asthma treatment strategies offer biological drugs as an alternative. Monoclonal antibodies, drugs targeting IgE-dependent mechanisms, IL-5, ­IL-4, IL-13, IL-33, anti-alarmin agents, etc. are considered. The focus of special attention in the optimal use of biological therapy for asthma is proper immune endotyping, development of appropriate biomarkers, determination of the main immunological mechanism for choosing the right targeted therapy. Much attention is now being paid to the molecular aspects of asthma. In-depth knowledge of allergenic structures has led to molecular component diagnostics, which has led to a better understanding of patient sensitization. Molecular-oriented diagnostics is used to determine the best approach to allergen-specific immunotherapy.

Хронічний гастродуоденіт (ХГД) у дітей являє собою одне з найпоширеніших захворювань травного тракту, а його терапія потребує удосконалення. Мета - вивчити ефективність застосування Lactobacillus rhamnosus GG ATCC 53103 (LGG) у комплексній терапії дітей з ХГД та впливу лікування на експресію генів про- та протизапальних цитокінів, факторів транскрипції Т-лімфоцитів у слизовій оболонці букального епітелію. Матеріали та методи. Обстежено 39 дітей, хворих на хронічний гастродуоденіт, віком 10-14 років, з яких сформовано 2 групи порівняння. До основної групи (n=21) увійшли пацієнти, для лікування яких, поруч із традиційною терапією, застосовано пробіотичний препарат, що містив 5×109 ліофілізованих життєздатних бактерій LGG. Контрольну групу (n=18) склали хворі, які отримували лише традиційну терапію. Тривалість застосування пробіотичного препарату LGG становила 14 діб. Для встановлення ефективності застосування LGG у терапії визначено рівень експресії мРНК-факторів транскрипції (Tbet, RORyt, FOXP3) T-клітин та інтерлейкінів (IL-1β, IL-17α, IL-10) за допомогою полімеразної ланцюгової реакції зі зворотною транскрипцією. Результати. Загострення ХГД характеризувалося підвищенням у букальній слизовій оболонці рівня експресії мРНК-фактора транскрипції RORyt Th17-клітин та мРНК IL-1β, IL-17α. Після стандартної терапії в дітей з ХГД виявлено достовірне підвищення активності експресії мРНК-фактора транскрипції Tbet Th1-клітин та зниження активності експресії мРНК-фактора транскрипції RORyt Th17-клітин. У дітей після лікування комбінованою терапією із застосуванням пробіотичного препарату, що містить LGG, спостерігалося зниження активності експресії мРНК-фактора транскрипції RORyt Th17-клітин, і, на відміну від дітей, що отримали стандартну терапію, ще відзначався низький рівень мРНК-фактора транскрипції Tbet Th1-клітин і мРНК IL-17α; у поєднанні з підвищеним рівнем мРНК-фактора транскрипції FOXP3 Treg-клітин. Висновки. Призначення комбінованої терапії із застосуванням пробіотичного препарату, що містить Lactobacillus rhamnosus GG у дітей з ХГД, сприяє найшвидшому регресу клінічних проявів: больового, диспептичного синдромів. Призначення LGG приводить до швидшого зниження рівня експресїї генів IL-17α за рахунок збільшення активності експресїї мРНК-фактора транскрипції FOXP3 Тreg-клітин. Дослідження виконано відповідно до принципів Гельсінської декларації. Протокол дослідження ухвалено Локальним етичним комітетом зазначеної в роботі установи. На проведення досліджень отримано інформовану згоду батьків дітей. Автори заявляють про відсутність конфлікту інтересів.

In recent years, the problem of hyperprolactinemia in children remains relevant because it is one of the most common pathologies of the hypothalamic-pituitary system, causing impaired fertility and reproductive function in adulthood. According to population studies, its incidence is 0.5 % in females, exceeding this figure in males by 10 times. Prolactin has: immunomodulatory effect, enhancing lymphocyte proliferation, phagocytic capacity of macrophages, IgA synthesis; analgesic effect; promotes postnatal growth of the body by inducing the activity of genes associated with growth; activates the proliferation of keratinocytes, epithelial cells of the prostate; participates in the regulation of metabolism, water-electrolyte balance, inhibiting the excretion of potassium and sodium ions by the kidneys; influences human behavior by accelera­ting neurogenesis, memory, learning and providing neuroprotection; induces surfactant production; stimulates lipogenesis. Prolactin le­vels increase due to physiological hyperestrogenemia, which blocks the inhibitory effect of dopamine on prolactin secretion and occurs during lactation, pregnancy and some other physiological states. Pathological hyperprolactinemia occurs in children with se­condary hypogonadotropic hypogonadism, organic lesions of the suprasellar area of the brain and may be secondary (symptomatic). In the etiological structure of hyperprolactinemia syndrome, the largest proportion (60 %) in children and adolescents belongs to prolactinomas (pituitary adenomas that secrete prolactin), idiopathic hyperprolactinemia (22.7 %) and iatrogenic hyperprolactinemia induced by 6 drugs (4 % of cases). Given that the lion’s share of hyperprolactinemia in childhood is associated with the presence of pituitary prolactinoma, characterized by latent gradual progression of reproductive disorders, growth processes and neurological symptoms, the objective of this article is to focus on the pleiotropic effects of prolactin in the body, which controls more than 300 biological functions, epidemiological, etiological and pathogenetic mechanisms, on the features of the clinical classification of hyperprolactinemia to form a modern understanding of this problem.

Атопічний дерматит (АД) — найчастіше хронічне алергічне захворювання в дітей, патогенез якого базується на ендогенних генотипах та який проявляється різними клінічними фенотипами — ізольованим та поєднаним з іншими формами атопії — алергічним ринітом / ринокон'юнктивітом (АР/АРК) і/або бронхіальною астмою (БА). На цей час одним із найбільш вивчених генетичних маркерів ризику розвитку АД є однонуклеотидні поліморфізми гена філагріну (SNP FLG), зокрема, rs_7927894. Базовим біомаркером АД є загальний сироватковий імуноглобулін Е (IgE). Але дотепер не було комбінованого дослідження цих предикторів маркерів при різних фенотипах АД у дітей. Мета — визначити варіанти генотипу SNP rs_7927894 гена FLG та сироваткових концентрацій загального IgE як персоніфікованої панелі предикторів ризику розвитку різних клінічних фенотипів АД у дітей. Матеріали та методи. У дослідженні взяли участь 2 групи пацієнтів: основну групу становили 39 дітей, хворих на фенотипи ізольованого АД та АД, поєднаного з АР/АРК/БА; контрольну — склали 47 дітей із захворюваннями травної системи (функціональна диспепсія, хронічний гастрит, виразкова хвороба, функціональні розлади біліарної системи) без клінічних ознак атопії. Пороговим рівнем статистичної доcтовірності прийнято p173 МО/мл. Також встановлено персоніфіковані предиктори — генотип і біомаркер для ризику розвитку фенотипу АД, поєднаного з АР/АРК/БА: 2,88 (95% ДІ 1,07; 8,54; p213 МО/мл. Додатково визначено ризик розвитку фенотипу АД, поєднаного з АР/АРК/БА порівняно з ізольованим АД при пороговій концентрації загального IgE>1001 МО/мл: 16,00 (95% ДІ 2,68; 95,44; p173 МО/мл для фенотипу ізольованого АД і при сироваткових концентраціях >213 МО/мл для фенотипу АД, поєднаного з АР/АРК/БА. Рівень загального сироваткового IgE>1001 МО/мл є достовірним біомаркером(предиктором ризику розвитку фенотипу АД, поєднаного з АР/АРК/БА, порівняно з фенотипом ізольованого АД у дітей. Дослідження виконано відповідно до принципів Гельсінської декларації. Протокол дослідження ухвалено Локальним етичним комітетом усіх зазначених у роботі установ. На проведення досліджень отримано інформовану згоду батьків дітей. Автори заявляють про відсутність конфлікту інтересів.

Background. At present, total immunoglobulin E, which has been used as a basic biomarker of atopy for several decades, in most cases does not reflect the severity of allergic inflammation in the skin in children suffering from atopic dermatitis (AD). Therefore, there is a need for new serum biomarkers that would allow to accurately diagnose the severity degree, control the course of AD and prevent its transformation into phenotypes in combination with other atopic diseases (AtD). In the past two decades, a new biomarker of the inflammation severity degree in the skin within AD — thymus- and activation-regulated chemokine (TARC/CCL17), associated with T-lymphocytes type 2 has been actively studied. The purpose of the study was to determine the associations of serum concentrations of TARC/CCL17 with the AD in children: age, severity, and AD phenotypes — isolated and combined with comorbid AtD. Materials and methods. The basic group comprised 39 children with atopic dermatitis aged 3–6, 7–11, and 12–18 years old. The phenotypes of the basic group were AD isolated and combined with comorbid AtD — seasonal allergic rhinitis/rhinoconjunctivitis, and/or perennial allergic rhinitis, and/or bronchial asthma. The control group comprised 47 children with gastrointestinal pathology without clinical signs of atopy. The severity of AD in children of the basic group was determined using the scoring atopic dermatitis index (SCORAD). Results. Significant direct associations of TARC/CCL17 with the AD severity and the SCORAD index, which is a clinical marker of AD severity, were determined. A reverse association was found between TARC/CCL17 and the age of patients in both the basic and control groups. Also, significant associations were found with the patients’ age increase, with the development of the AD phenotype combined with comorbid AtD and male gender (reverse significant association between age and female gender). Conclusions. TARC/CCL17 is significantly associated with the severity degree increase in patients with AD of all the phenotypes — isolated and combined with comorbid AtD. With the age increase, the level of TARC/CCL17 decreases, AD has a trend to progress into phenotype combined with other AtDs, and the incidence increases among male patients. The use of TARC/CCL17 in the diagnostic process of atopic dermatitis in children will provide more personalized control and prevention of progression of the disease into phenotypes combined with other atopic diseases.

У літературному огляді наведено сучасні уявлення стосовно затримки внутрішньоутробного розвитку (ЗВУР) як однієї з причин перинатальної захворюваності та смертності. Незважаючи на розвиток нових способів діагностики, лікування, профілактики, показник частоти ЗВУР зберігає тенденцію до зростання. Серед дітей зі ЗВУР відзначається високий рівень ускладнень у будь-якому віці. Рання діагностика супутніх захворювань у дітей зі ЗВУР становить великий інтерес у зв'язку з появою нових методів діагностики. У статті висвітлено особливості імунної відповіді в новонароджених і зокрема у дітей зі ЗВУР. Наведені дані свідчать про превалювання в новонароджених неспецифічної імунної відповіді над специфічною, переважання генералізованого характеру запалення, знижену активність фагоцитів, нейтрофілів, специфічних антигенпрезентуючих клітин (APCs) у відповідь на більшість агоністів Toll-подібного рецептора (TLRAs), високий рівень інтерлейкіну-6 та інтерлейкіну-23. Незважаючи на те, що в дітей зі ЗВУР порівняно з дітьми з масою тіла, що відповідає терміну гестації, відмічаються відносно низькі рівні інтерлейкіну-6 та інтерлейкіну-8 після народження, проаналізовані літературні джерела свідчать про те, що рівень цих цитокінів стрімко підвищується на другому тижні життя. Підвищення рівня прозапальних цитокінів за системного запалення є прогностично несприятливим чинником перебігу захворювання. В огляді висвітлено інформацію щодо наявності мікроРНК у грудному молоці. МікроРНК — малі некодуючі РНК завдовжки 19–23 нуклеотиди, що регулюють експресію таргетного гена. МікроРНК грудного молока стійкі до ферментів шлунково-кишкового тракту дитини і переважно абсорбуються. Проаналізовано джерела, що доводять зміну траскриптому мікроРНК грудного молока залежно від термінів гестації, характеру перебігу пологів, дієти матері, вживання нею лікарських препаратів. За наведеними дослідженнями найбільш представлені в ранні терміни лактації мікроРНК грудного молока (miR-155, miR-148a, miR-146b, miR-181a, miR-181b, miR-17) імовірно змінюють рівень про- і протизапальних цитокінів, регулюючи гостроту імунної відповіді дитини. Дослідження мікроРНК грудного молока матері може відігравати важливу роль у прогнозуванні можливих ускладнень запального характеру в дитини зі ЗВУР. У роботі використано бази даних Scopus, Web of Science, MedLine, PubMed, Google Scholar, CyberLeninka, РІНЦ. Автори заявляють про відсутність конфлікту інтересів. Ключові слова: затримка внутрішньоутробного розвитку, ЗВУР, мікроРНК, грудне молоко, імунна відповідь, імунітет, огляд.

The article deals with the experience of remote teaching of pediatrics to the fourth year medical students at the Department of Pediatrics 1 and Medical Genetics of Dnipropetrovsk Medical Academy in quarantine time due to the COVID-19 pandemic. The attention of educational institutions to distance learning has increased; due to the introduction of remote teaching it became possible to create educational and scientific sources that are several times greater than the capabilities of paper media. Clinical departments of medical universities have the opportunity to expand their experience in the application of the latest information technologies and for the first time to introduce the teaching of online clinical disciplines. The article describes the experience of preparing and conducting practical classes, teaching lecture material. The dynamics of changes in the load on teachers and students in the process of gaining distance learning experience is described. The stages of preparation of educational materials, tests and clinical tasks for students are described. Possibilities of using tests from KROK-2 base in the preparation of students for practical sessions are considered. Options for testing the knowledge obtained by students during preparation for practical classes are presented. The article examines in detail the possibilities of conducting practical classes and lecturing on various platforms presented on the Internet, the possibility of identifying students, as well as various forms of communication between student and teacher. Attention is also paid to the procedure and methods of accepting students’ classes, which were missed before the quarantine period. The Department of Pediatrics 1 and Medical Genetics also shares the experience of conducting methodological meetings of the department, student research group and educational activities that may also take place in the work of the department during quarantine measures in the COVID-19 pandemic.

Currently, issues related to tight junction dysfunction, are one of the most relevant and studied in scientific world. In spite of significant achievements, many problems are still open today. This review discusses the molecular structure and regulation of stomach tight junctions, the relationship between Helicobacter pylori and food allergy in children and the possibility of pharmacological regulation of paracellular permeability of the gastric mucosa. To write the article, information was searched using Scopus, Web of Science, MEDLINE, PubMed and Google Scholar databases.

The article of the team of scientists of pediatricians and organizers of pediatric health care of Ukraine is devoted to the study of the main trends in the health status of children over last 22 years. The results of the analysis of the incidence and prevalence of diseases among Ukrainian child population, infant mortality rates over the past two decades demonstrates that they remain significantly higher than the average European indicators against the background of a progressive decrease in the number of child population at 3,16 million people. The prevalence of childhood diseases in Ukraine over past 22 years has grown by 41 %, the incidence of childhood diseases arose by 36 %. The article considers the ways of solving a number of new social and medico-ecological problems that negatively affect child health.

Досліджено рівень антимікробних пептидів у сироватці крові 35 дітей з аденоїдитом, асоційованим із гіперплазією ретроназальної мигдалини. Установлено, що в дітей із гіперплазією ретроназальної мигдалини відбувається зниження вмісту в сироватці крові кателіцидину LL-37, сурфактантного білка SP-D, бактерицидного білка, що посилює проникність клітин, та підвищення рівня лактоферину. Доведено, що порушення продукції антимікробних пептидів є одним із патогенетичних факторів розвитку хронічного запалення в носоглотці при гіперплазії ретроназальної мигдалини в дітей. При цьому вираженість даних змін залежить від ступеня гіперплазії ретроназальної мигдалини та максимально проявляється при аденоїдних вегетаціях 3-го ступеня. Фактором компенсації, спрямованим на відновлення адекватної імунної реактивності в дітей із гіперплазією ретроназальної мигдалини, є розвиток гіперплазії піднебінних мигдалин, що необхідно враховувати при плануванні обсягу лікувальних заходів.