(to the seventieth anniversary)

 

The article considers the key problems of the transition of the national health-care system to a new platform of personalized medicine and, in particular, pediatrics. The first part, published in this issue, analyzes the most important of the necessary aspects of the infrastructure of the new model. Evidence is given of the extreme urgency of introducing a new model of predictive, preventive and personalized medicine (PPPM). The result of implementation should be breakthrough success in solving many epidemiological, diagnostic, curative, preventive, social and economic problems. It is emphasized that neonatology and pediatrics are the most important link in this paradigm. When considering the potential architectonics of the model, important characteristics of its main segments are revealed. Diagnostic principles (genotyping, targeting, and dynamic screening of biomarkers) and arsenal (genomics, proteomics, metabolomics, mathematical modeling tools, etc.) of personalized medicine are presented. Attention is focused on the need to create information (global, regional and target-specific) banks that are necessary for monitoring individual health. The need to create a new social decision-making mechanism for selecting a preventive protocol that minimizes the risks of the disease or prevents its development is discussed. Four categories of basic programs of medical and social support of persons from the risk category are considered. The necessary conditions for translating these programs into practice are presented. The main tasks and problems of developing the principles for the preparation of preventive-prophylactic and protocols of medical rehabilitation for personalized medicine were discussed. 

Improving the health status of the population at the moment is a global problem widely discussed at the highest level in all regions of the globe. The main tasks of the international health-care organizations are to develop a strategy aimed at increasing the level of health and life expectancy, in particular, by reducing the infant morbidity and mortality, as well as finding the best tactics for nursing the infant in case of premature birth.

The data presented in the article demonstrate the variety of risk factors and mechanisms of early birth, social, economic, medical, genetic factors affecting the course of pregnancy and childbirth are covered, modern variants for the classification of prematurity and the dynamics of data of Russian and foreign statistics on the tendency of infant mortality rates are given, frequency of premature birth and survivability of premature infants is discussed in detail.

The main objective of the study of these factors is the development of preventive (prophylactic) measures in relation to prematurity, the introduction of modern technologies to predict, prevent and adequately manage premature births to reduce infant morbidity, and to find the optimal tactics for nursing a child in the event of premature birth.

Hypertrophic cardiomyopathy is the most common form of cardiomyopathy, occurring in childhood, occurring when a gene is mutated that encodes proteins of sarcomeric and non-sarcomeric complexes. The diagnosis of the disease is based on the data of echocardiography, revealing structural changes in the heart muscle according to the type of hypertrophy, while the genesis of these changes remains unclear. The causes of hypertrophic cardiomyopathy in childhood are diverse. Of great importance is the early diagnosis of metabolic forms of hypertrophic cardiomyopathy, so in some cases regress of hypertrophy is possible against the background of enzyme-substitution or other drug therapy. The article presents a clinical (cardiac and extracardiac symptoms) and laboratory markers of hypertrophic cardiomyopathy with mutations of genes of proteins of the sarcomeric complex, congenital metabolic disorders (glycogenoses, lysosomal pathology, fatty acid metabolism disorders, and mitochondrial diseases), genetic syndromes (Noonan, LEOPARD, Costello, cardio-fascial-cutaneous), neuromuscular diseases. The criteria for differential diagnosis of genetic forms of hypertrophic cardiomyopathy and myocardial hypertrophy in athletes are presented. 

In the era of modern medicine fundamental scientific installation is emerged in the diagnosis of diseases of the kidneys, which are based on traditional diagnostic tools. The presented article describes the modern view on the possibility of diagnosis of kidney diseases, based on genetic studies. The necessity of active development for molecular diagnostic methods of kidney diseases is revealed, which not only complement the traditional methods of research, but also provide insight in point of view of the molecular pathophysiology. Further study of kidney diseases from a position of molecular biology will allow us to take a modern look at the pathogenesis of many diseases and solve a number of problems from the standpoint of personalized therapy that takes into account the genetic characteristics of the patient. 

The questions of the ontogeny of a child’s sleep, starting with the stage of fetation, are considered. Data on the formation of certain fetal conditions that are analogues of fast and slow sleep in the postnatal period are given. The most important neurobiological preconditions for the formation of the child’s behavioral states are discussed, beginning with the neonatal period and until adolescence. Information on the specifics of the formation of periods of sleep and waking in infants, born in the outcome of premature birth, is presented. Changes in the bioelectrical activity of the brain in various states of the child at different stages of ontogeny are considered. The rationale for the risk of forming certain variants of sleep disorders in children of different age groups is given. The Russian-language version of the standardized questionnaire Child’s Sleep Habits Questionnaire (CSHQ), designed to detect sleep disorders in preschool and school-age children on the basis of parents’ questionnaires, is developed. 

Objective: to analyze the clinical course of ventilator-associated pneumonia caused by Stenotrophomonas maltophilia in infants as a high-risk group for the development of hospital acquired infection, as well as a study of the sensitivity of the pathogen to antibiotics.

Eighteen infants (14 premature and 4 mature infants) with ventilator -associated pneumonia due to (Stenotrophomonas maltophilia) were monitored. The disease occurred in the majority (72%) of infants as a monoinfection, more often in severe and acute form with severe toxicosis, trophic disorders, severe respiratory failure, bilateral lung and bronchial lesions. In 33% of children, mostly premature, there was a change in the pathogen, which increased the severity and duration of the disease. Pneumonia had complications in the form of sepsis (6%) and bronchopulmonary dysplasia (28%). Most Stenotrophomonas maltophilia retained sensitivity to ticarcillin + clavulanate, ciprofloxacin, chloramphenicol and co-trimoxazol.

For abstract to evaluate the clinical adaptation and immunological parameters in infants with severe hypoxic-ischemic lesions of the central nervous system, we examined small premature, extremely low birth weight (ELBW) infants with gestational age (GA) of 24 to 27,6 and infants with gestational age of 28 to 31 weeks (group 1, n=26 and group 2, n=16). The control group consisted of 15 full-term babies with uncomplicated early period of adaptation, born from apparently healthy women. The immune system of preterm infants at birth, regardless of their gestational age and birth weight, is characterized by decrease of the absolute number of white blood cells, increase of the percentage of lymphocytes and the number of NK-cells, as well as the prevalence of Th1-dependent immune response (increased level of γ-interferon against decrease in levels of interleukine – 1β and interleukine – 4). A specific feature of the immune response of extremely low birth weight infants is abnormal interaction between innate immunity cells and adaptive immunity cells, which is manifested in reduction of the percentage of regulatory CD4+ cells associated with inhibition of the functional activity of T-cells (CD4+CD25+) and monocytes (CD14+HLA-DR+). The decrease in the number of circulating ferritin levels indicates a predisposition of extremely premature infants to viral and bacterial infections. 

A continuous research for the study of disability among the infants of the Ivanovoregion, born weighing less than 1500, for the period from 2009 to 2013, is conducted. Analyzed all outcomes in disability (n=50) of all children (n=411), born and living in the Ivanovo region for the period of the assessment rate of establishing disability, gender-sensitive, disability structure, the frequency of occurrence of certain clinical entities that caused the disability, basic kinds violations of life and types of persistent disorder of body functions. The frequency of establishment of disability of children with birth weight less than 1500 was 12.17%, among children with extremely low birth weight (ELBW) – 17.7%, among children with very low birth weight (VLBW) – 10.07%. In children with extremely low birth weight, compared with children with very low birth weight, risk of developing a disabling pathology is higher (OR 1.9; 95% CI 1.041 – 3.546). In the structure of disability in the first place in the group of children with extremely low birth weight, and in the group of children with very low birth weight risk are diseases of the nervous system, on the second – congenital anomalies (malformations), deformations and chromosomal abnormalities, and the third – respiratory diseases. Thus, for the first time set the frequency and causes of disability of infants born with extremely low birth weight and very low birth weight, at the level of the constituent of theRussian Federation. 

The article is devoted to a rare pathology from a group of accumulation diseases with an autosomal recessive type of inheritance – mucolipidosis II and IIIA types. The disease is characterized by a greater phenotypic similarity to mucopolysaccharidosis.

Objective: analysis of genophenotypic parameters in Russian patients with mucolipidosis II and IIIA types. The activity of lysosomal enzymes in plasma (β-glucuronidase, total hexosaminidase and N-acetyl-α-D-glucosaminidase) was measured using a standard technique using chromogenic and fluorogenic substrates. Genomic DNA of peripheral blood leukocytes was isolated using a set of reagents Preb 100 (DIAtomTM). Amplification of all exons of the GNPTAB gene was carried out by polymerase chain reaction (PCR) followed by direct non-radioactive sequencing by Sanger.

50 patients aged from 1.5 to 10 years were examined. The clinical symptoms of the disease included: a Hurler-like phenotype, growth retardation, skeletal, cardiac and vascular damage, and CNS. Mucolipidosis type II (I-cell disease) was characterized by a more severe course. The clinical diagnosis was confirmed by the results of laboratory methods of investigation: normal parameters of renal excretion of glycosiminoglycans (GAG), high (5-15 times higher than normal) activity of lysosomal hydrolases in blood plasma and detection of mutations in the GNPTAB gene.

35 probands are completely genotyped. In 8 patients only 8 mutant alleles were detected; 7 mutations were not detected. Six new mutations in exons 1 (p.I31N; p.Q36P), 10 (p.L398P), 11 (p.W446X) and 13 (p.S738X; c.2250delT) were found, including a frequent mutation for Russian patients P.S738X (21% alleles). The most common (31.4% alleles) in the Russian cohort of patients was a known small deletion c. 3503_3504delTC, leading to a reading frameshift.

A clinical observation of a child with type 2 mucolipidosis (I-cell disease) with typical symptomatology of the disease caused by two nonsense mutations of the GNPTAB gene is presented: p.S738X / p.R375X.

In conclusion, it is emphasized that the identification of mutations of the GNPTAB gene provides prediction of the severity of the disease course, an understanding of the mechanisms of its development that will contribute to the development of pathogenetic treatment methods, improving the quality of life of patients and effective medical and genetic counseling.

The article presents literature data and a clinical case on the rare Imerslund-Grasbeck syndrome. The pathogenetic foundations, the features of the clinical picture, course and treatment of this syndrome in children are discussed. Own clinical observation of the syndrome of Imerslund-Grasbeck in a 8 years girl is presented. We presented a summary table with described in the literature of mutations in different ethnic groups. The authors indicated the need for molecular genetic studies of genes CUBN and AMN in children with the combination of proteinuria and B12-deficiency anemia to diagnose the Imerslund-Grasbeck syndrome. Patients with the Imerslund-Grasbeck syndrome require lifelong replacement therapy with cobalamin, observation by a nephrologist and a hematologist. 

Questions of relevance and timeliness of diagnostics of perinatal disturbances of the central nervous system in newborns are considered in the article. Research objective was to determine the reliable recognition of the development of newborn encephalopathy at the age of the first two weeks of life according to neurological examination and neurosonography parameters with Doppler study of cerebral vessels. Features of the neurology status and data of ultrasonic examination of brain with Doppler study of cerebral vessels in 58 newborns with pathology of the nervous system and 23 healthy newborns are investigated. 10 sings of the neurological status and 10 parameters of ultrasonic examination are analyzed. By results of the obtained findings, prognostic rule is developed, governed by application of discriminant analysis of the studied signs, allowing to diagnose encephalopathy in newborn with sensitivity and specificity of 95% in the first week of life. Its application promotes timely identification and the beginning of therapy at infants from risk group of development of severe neurological dysfunction and preventing the growth of disability among infants.

Our research objective was to evaluate the importance of neurophysiological methods in diagnosing the state of visual, somatosensory and motor pathways condition in the early stages of multiple sclerosis (MS) and acute disseminated encephalomyelitis (ADEM) in children.

Materials and methods. Twenty-four children with a debut of multiple sclerosis, 15 children with debute of acute disseminated encephalomyelitis and 20 neurologically healthy children of the comparison group were examined. All patients were evaluated by neurologist, brain MRI and CSF analysis (isoelectrofocusing to oligoclonal IgG, oligoclonal bands test), visual evoked potentials (VEP), transcranial magnetic stimulation (TMS) and somatosensory evoked potentials (SSEP).

Results. In children with MS asymmetry of the conduction along the motor pathways on the spinal level was higher than in patients with ADEM and controls, functional state of somatosensory cortex neurons was lower and conduction along somatosensory pathways on the spinal level was slower – all differences significant. According to the visual evoked potentials, in more than half of the cases, there was an increase in the latency of the P100 peak. Also in MS group there was a significant disruption of the visual pathway in 54% of the cases. Neurophysiological changes in 58% of cases were demyelinating, and violations of the axonal type occurred in 37% of cases.

Conclusions. Neurophysiological diagnostic methods such as transcranial magnetic stimulation, visual evoked potentials, somatosensory evoked potentials are highly informative for the differential diagnosis of multiple sclerosis and acute disseminated encephalomyelitis. More pronounced spinal lesions in early stages of MS than in ADEM in children may be the cause of the neurophysiologic differences, and prevalence of the sensory system involvement at this stage may be the reason behind more extended SSEP abnormalities comparing with TMS. VEP changes may reflect primary demyelinating course of the disease on the early stages of MS. VEP, SSEP and TMS may be recommended as standard way of evaluation and diagnostic of ADEM and MS in children. 

Atopic dermatitis (AD) takes special place in the structure of allergic diseases as it is one of the most prevalent and very first allergic manifestation, it often transforms into other allergic forms, decreases children’s life quality independent of the age and also needs long term and staged treatment. Purpose of work is to establish the status of immune status parameters and mediators of allergic inflammation and to assess the diagnostic capabilities of dermatoscopy and ultrasound examination of the skin in children with atopic dermatitis. Parameters of cellular and humoral immunnity, cytokine status, inflammatory mediators, morphological features of skin changes according to results of dermatoscopy and ultrasound examination were investigated in 128 children with atopic dermatitis aged from 1 to 18 years. Assessment of clinical course’s severity of atopic dermatitis was conducted by semiquantitative method using SCORAD index. In this article presents the results of immunological examination in children with AD and in healthy children aged from 1 to 18 years. Changes of parameters of cellular, humoral immunity, cytokine status and serum immunoglobulins dependent on severity of clinical course were found in children with atopic dermatitis. Atopic dermatitis is a chronic disease with very polymorphic manifestations in skin. According to the results we can conclude about presence of several dermatoscopy variants of skin damage on background of atopic dermatitis. In the study of echograms of skin areas affected by atopic dermatitis was noted thickening of all layers of skin, presence of hypoechoic wide band between the epidermis and the derma, diffuse decrease of derma echogenicity. Immunogram, dermatoscopy and ultrasound diagnostic of skin can be used in diagnostic process for verification and clarification of clinical diagnosis, evaluating of treatment effectiveness and examination of medical services quality. 

Health is one of the main conditions that determine the adequate child development. Work objective: to find out the state of health of the children of the city and the changes in these parameters for 16 years. The method of research is the questionnaire survey of parents of children from one year to 17 years. The questionnaire contains 20 questions and 94 answer choices, which are statically processed in comparison with the results of a similar study in 2000.

Results and conclusions: 582 respondents were questioned. The findings indicate a change in the health status of children. Over the past 6 years, the number of children breastfed up to one and a half years has increased and the number of children receiving breastfeeding for 1 to 3 months has decreased. A number of factors have been identified that negatively affect the health of children: infection pregnant, pathological pregnancy, short duration of breastfeeding, previous illnesses, smoking during pregnancy and in the home, a negative attitude toward vaccinations, and a long time spent with electronic equipment.

The article is dedicated to one of the urgent problems of modern medicine – osteoporosis. Modern trends in the national epidemiology, risk factors, and diagnostic approaches are discussed. Particular attention is paid to the ambiguity and inconsistency of information on osteoporosis in childhood and adolescence, as well as the lack of convincing studies of this issue in children’s sports medicine. The authors conduct an analysis of the generally accepted approaches to the identification of risk groups for the development of osteoporosis in children, the predisposing factors and complex issues of diagnosing this condition are discussed in detail. The publication presents the results of our own observations of the most complex clinical cases in a group of children and adolescents involved in sports, including elite sports. A separate section is devoted to the analysis of pharmacological agents for the prevention and treatment of osteoporosis in children and young athletes. All presented data are in accordance with the legislation and rules of the World Anti-Doping Agency (WADA, 2017). 

The article presents the basic information relating to the clinical and immunological features of ixodes tick-borne borreliosis in children living in the Primorsky region. Research objective: to to analyze the effectiveness of the inclusion to the treatment scheme meglumine acridon acetate (cycloferon in pills) for the treatment of children with ixodes tick-borne borreliosis.

The study included 55 children with ixodes tick-borne borreliosis at the age of 4–12 years: 25 children of the main group and 30 children of the comparison group who received traditional therapy. In the treatment scheme of children of the main group, the drug meglumine acridon acetate (cycloferon) was included. The use of cycloferon in the complex therapy of patients with ixodes tick-borne borreliosis resulted in a reduction in the duration of the manifestation of the main clinical symptoms of the disease, facilitated the synthesis of serum interleukine IL-10 by blood cells and inhibited the production of interleukine-1α and γ-interferon, which led to a faster formation of Th1 / Th2 type Immune response. Positive dynamics during treatment persisted in the study of the catamnesis of the patients observed for 5 years after the disease. There were no cases of chronic ixodes tick-borne borreliosis. 

The article discusses issues related to the early stages of the formation of food behavior, which are of particular interest, given their close connection with the socially significant problems of the present – obesity, metabolic syndrome, cardiovascular disease, etc.

The ability to perceive the sensations of taste is revealed already in the prenatal period. The main importance for the formation of taste has a genetic predisposition, predetermining the perception of taste, consistency and flavor, as well as the frequency and speed of food intake. The role of environmental factors that can influence the expression of genes of the taste receptors of GPCRs, as pre- and postnatal, is discussed.

The influence of taste diversity at early stages of development on taste perception in subsequent periods of life is considered. The influence of complementary feeding on the formation of food preferences and, in particular, the influence of a sufficient presence of fruit and vegetable in the complementary feeding on their consumption at school age is presented. The significant role of the family and the psychological component of the process of feeding in the formation of food behavior were noted. 

The article describes the electronic educational resources – multimedia training system for congenital malformations and developmental anomalies. The work objective is an integrated approach to self-training and testing that combines the traditional principle of the control of knowledge and graphic tests with animation elements that provides high-quality remote to increase knowledge. We describe the structure of the system, screenshots, as well as Web-technology used for its development. The functionality of the system and the experience of Internet-based applications to improve the skills of doctors and students are given training. Criterion for assessing the level of knowledge of students on the basis of test results, taking into account the complexity of tests offered have been proposed. Evaluating the effectiveness of the use of distance training system allows us to conclude that multimedia training system «Congenital malformations» can be successfully applied for remote medical information support medical genetic counselors and physicians of different specialties involved in diagnosing congenital malformations in children and for training students – future doctors.