[Morphological features of an optic nerve in premature infants according to the optical coherence tomography data]. / Morfologicheskie osobennosti zritel'nogo nerva u nedonoshennykh detei po dannym opticheskoi kogerentnoi tomografii.

OBJECTIVE: To assess the morphological state of the visual analyzer in premature infants in long-term. MATERIAL AND METHODS: We examined 40 premature children (74 eyes) aged 10.3±2.92 years (gestational age (GA) 25-34 weeks, birth weight (BW) 690-2700 g). Twenty mature children (40 eyes), aged 10.8±3.05 years, were examined as a control group. The children underwent standard ophthalmologic examination, optical coherence tomography (OCT) and recording of visual evoked potentials (VEP). RESULTS: The thickness of retinal nerve fiber layer (RNFL) is less in preterm infants than in term infants, regardless of retinopathy of prematurity (ROP) and refraction (p<0.05). Thickness loss has an inverse proportion with the degree of hypoxic-ischemic encephalopathy (HIE) and intraventricular hemorrhage (IVH) (p<0.05). Retinal thickness in fovea is significantly greater in preterm infants and has a direct proportionality with the degree of IVH and the number of days on artificial lung ventilation (p<0.05). Moderate organic changes were detected in conduction pathways in 43.08% of premature infants according to VEP data. CONCLUSION: The use of OCT and recording of VEP may improve the quality of comprehensive neuro-ophthalmologic diagnosis in preterm infants. The thickness loss of RNFL can be expected in premature infants with HIE and IVH.

Optimizing the Intensive Care Treatment of Severe and Complicated Plasmodium falciparum Malaria in Nonimmune Patients.

This study analyses the intensive care treatment of 48 patients admitted to the Intensive Care Unit (ICU) at the Infectious Diseases Clinical Hospital No. 2, Moscow, Russia, between 2007 and 2019, with a severe and complicated form of P. falciparum malaria (B50.8 ICD 10). Objective. The aim of this study was to improve the intensive care treatment for severe and complicated P. falciparum malaria. The treatment strategy implemented was aimed at preventing ischaemia-reperfusion injury to organs, as well as haemorrhagic complications. The ICU Case Management Protocol set up indications for transferring patients to the ICU which provide preventive (prior to the development of renal failure) application of extracorporeal hemocorrection methods (continuous venous-venous hemodiafiltration and plasmapheresis in a plasma exchange mode) and mechanical ventilation under a medically induced coma, given impaired consciousness as the initial symptom of patients. Results. Successful treatment outcome in a majority of the patients (93.8%), shorter ICU length of stay (6.67 ± 1.9 days as compared to 94 ± 1.6 before introduction of the protocol), a median parasite clearance time of 37.50 hours (95% CI 36.21-38.18), and a reduced mortality rate from 29.1% to 6.25% support the efficacy of the ICU protocol in managing severe and complicated P. falciparum malaria.

Genetic Specificity of the Siberian Forest Reindeer (Rangifer tarandus valentinae Flerov, 1932) of the Kuznetsk Alatau.

This is the first study to show the genetic identity of the Altai-Sayan population of the forest reindeer of the Kuznetsk Alatau (Rangifer tarandus valentinae). The population is characterized by the existence of unique mitochondrial lines, the absence of signs of introgression of domestic rein deer mtDNA, as well as a low level of genetic diversity. In the sample studied, only two nucleotide substitutions (both of them transitions) were revealed, the nucleotide diversity (0.0015 ± 0.00136) was almost ten times lower than in most populations of wild reindeer in Russia and was comparable only with that of some wild reindeer populations of Norway and Svalbard. The haplotype diversity (h) was also relatively low (0.615 ± 0.102).

Novel intronic variant in PALB2 gene and effective prevention of Fanconi anemia in family.

Despite the acceptance of NextGen sequencing as a diagnostic modality suitable for probands and carriers of Mendelian diseases, its efficiency in identifying causal mutations is limited by both technical aspects of variant call algorithms and by imperfect, consensus-based criteria for assessing the pathogenicity of the findings. Here we describe the medical history of the family with a child born with Fanconi anemia. In this case, typical diagnostic routines were complicated by unusual combination of mutations. PALB2 variant NM_024675.3:c.172_175delTTGT (p.Gln60Argfs) in maternal sample, previously classified as a definitely pathogenic frameshift mutation, was in compound heterozygous state with PALB2 NM_024675.3:c.3114-16_3114-11del (p.Asn1039Glyfs*7), which led to validated PALB2 exon 11 skipping event in paternal locus. Findings enabled the development of the PGТ and successful selection of two mutation-free embryos. We show that even in absence of definitive exome findings, clinician-guided research inquiries into the structure and function of the suspected loci allow definitive diagnosis. Described case provides an example of a crucial input of an investigational workflow in genetic prognosis and successful PGT.

[Epidemiological and clinical aspects of diagnosis, treatment and prophylaxis of imported malaria cases in Russian Federation].

Actually one of the main tasks of health workers in the field of the tropical diseases prevention (malaria) is early detection of malaria imported cases and efficacious treatment. In order to prevent the re-establishment of local malaria transmission by Anopheles mosquitoes from imported malaria cases, and fatal cases of disease there is develop and implement the Case Management Protocol of malaria diagnosis and treatment (2014, 2019) based on long-term experience of epidemiologists and clinicians, taking into account recommendations of WHO (2013, 2015). In this article the main principles of diagnosis and treatment of different malaria species Plasmodium falciparumand Plasmodium vivax-malaria, prophylaxis measures of autochthonous cases from imported cases of the word endemic region are discussed.

Antibiotics from Extremophilic Micromycetes.

Extremophilic microorganisms, which are capable of functioning normally at extremely high or low temperatures, pressure, and in other environmental conditions, have been in the focus of microbiologists' attention for several decades due to the biotechnological potential of enzymes inherent in extremophiles. These enzymes (also called extremozymes) are used in the production of food and detergents and other industries. At the same time, the inhabitants of extreme econiches remained almost unexplored for a long time in terms of the chemistry of natural compounds. In recent years, the emergence of new antibiotic-resistant strains of pathogens, which affect humans and animals has become a global problem. The problem is compounded by a strong slowdown in the development of new antibiotics. In search of new active substances and scaffolds for medical chemistry, researchers turn to unexplored natural sources. In recent years, there has been a sharp increase in the number of studies on secondary metabolites produced by extremophiles. From the discovery of penicillin to the present day, micromycetes, along with actinobacteria, are one of the most productive sources of antibiotic compounds for medicine and agriculture. Many authors consider extremophilic micromycetes as a promising source of small molecules with an unusual mechanism of action or significant structural novelty. This review summarizes the latest (for 2018-2019) experimental data on antibiotic compounds, which are produced by extremophilic micromycetes with various types of adaptation. Active metabolites are classified by the type of structure and biosynthetic origin. The data on the biological activity of the isolated metabolites are summarized.

Adipose may actively delay progression of NAFLD by releasing tumor-suppressing, anti-fibrotic miR-122 into circulation.

Nonalcoholic fatty liver disease (NAFLD) is the most common liver pathology. Here we propose tissue-cooperative, homeostatic model of NAFLD. During early stages of NAFLD the intrahepatic production of miR-122 falls, while the secretion of miRNA-containing exosomes by adipose increases. Bloodstream carries exosome to the liver, where their miRNA cargo is released to regulate their intrahepatic targets. When the deterioration of adipose catches up with the failing hepatic parenchyma, the external supply of liver-supporting miRNAs gradually tapers off, leading to the fibrotic decompensation of the liver and an increase in hepatic carcinogenesis. This model may explain paradoxical observations of the disease-associated decrease in intrahepatic production of certain miRNAs with an increase in their levels in serum. Infusions of miR-122 and, possibly, some other miRNAs may be efficient for preventing NAFLD-associated hepatocellular carcinoma. The best candidates for exosome-wrapped miRNA producer are adipose tissue-derived mesenchymal stem cells (MSCs), known for their capacity to shed large amounts of exosomes into the media. Notably, MSC-derived exosomes with no specific loading are already tested in patients with liver fibrosis. Carrier exosomes may be co-manufactured along with their cargo. Exosome-delivered miRNA cocktails may augment functioning of human organs suffering from a variety of chronic diseases.

Genetic characterization of Plasmodium vivax in the Kyrgyz Republic.

At the end of 2016, Kyrgyz Republic was certified by the World Health Organization as a malaria-free country, while only a decade ago this disease posed a serious health threat. The progress achieved by Kyrgyz Republic provides a unique example of tertian (Plasmodium vivax) malaria elimination. This success was based on an integrated approach, including measures for the treatment of infected people and disease prevention, vector control and the development of an effective national epidemiological surveillance system. Lower P. vivax msp-1, msp-3α, csp and dbpII genes polymorphism was revealed in Kyrgyz Republic in compare with that in Tajikistan. Molecular characterization of the causative agent found that P. vivax populations in Kyrgyz Republic was comprised by several lineages, highly divergent in the south-western and genetically homogeneous in the northern regions of Kyrgyz Republic, d. Such profile in the northern regions was compatible with several recent introductions rather than a long-term endemic circulation of the parasite. A low level of genetic variability suggested that the parasitic systems of tertian malaria, were not adapted, which, along with other factors, largely determined the possibility of malaria elimination in northern Kyrgyz Republic. Other determinants included environmental, social, and epidemiological factors that limited the spread of malaria. South-western Kyrgyz Republic, a region with a high level of interstate migration, requires considerable attention to prevent the spread of malaria.

[Genetic and biochemical features of the monogenic hereditary urolithiasis]. / Geneticheskie i biokhimicheskie osobennosti nasledstvennykh monogennykh form mochekamennoi bolezni.

Urolithiasis is a common urological problem. In most cases, this multifactorial pathology develops due to the combination of inherited low-penetrance gene variants and environment factors such as urinary tract infections and unbalanced diet. However, some cases are monogenic. These hereditary forms of urolithiasis manifest in childhood, and are characterized by multiple, bilateral and recurrent kidney stones and progress to chronic renal failure relatively early. Due to widening acceptance of exome and gene panel sequencing, substantially larger percentages of urolithiasis cases are now attributed to hereditary causes, up to 20% among patients of 18 years old or younger. Here we review genetic and biochemical mechanisms of urolithiasis, with an emphasis on its hereditary forms, including fermentopathies (primary hyperoxaluria, adenine phosphorobosyltransferase deficiency, phosphoribosyl-pyrophosphate-synthetase deficiency, xanthinuria, Lesch-Nihan syndrome) and these caused by membrane transport alterations (Dent's disease, familial hypomagnesia with hypercalciuria and nephrocalcinosis, hypophosphatemic urolithiasis, distal tubular acidosis, cystinuria, Bartter's syndrome). We suggest a comprehensive gene panel for NGS diagnostics of the hereditary urolithiasis. It is expected that accurate and timely diagnosis of hereditary forms of urolithiasis would enable the counselling of the carriers in affected families, and ensure personalized management of the patients with these conditions.

Effect of Type 2 Diabetes Mellitus on Five-Year Survival of Patients Hospitalized Because of Acute Decompensated Heart Failure.

OBJECTIVE: To assess the impact of type 2 diabetes mellitus (T2DM) on prognosis of patients hospitalized because of acute decompensated heart failure (ADHF). MATERIALS AND METHODS: We analyzed data of the hospital register of ADHF which comprised information on 735 patients (254 [35%] with T2DM) consecutively admitted in 2010-2011. Median follow-up was 1790 days. RESULTS: The presence of T2DM was associated with increased risk of death: during the index hospitalization due to ADHF (hazard ratio [HR] 1.7, 95% confidence interval [CI] 1.0-2.8), within 18 months (HR 1.4, 95% CI 1.0-1.8), and within 5 years (HR 1.3, 95% CI 1.0-1.5). CONCLUSIONS: T2DM is common among acute decompensated heart failure patients (up to 35% of cases). T2DM is an independent risk factor of death during the index hospitalization and over the next 18 months and 5 years.

Problems of clinical diagnosis and treatment of P. falciparum malaria in Russian Federation.

AIM: To study the causes of falciparum malaria deaths in Russian Federation and to optimize therapy for severe forms of the disease. MATERIALS AND METHODS: The analysis of falciparum malaria cases with deaths recorded in Russian Federation from 2013 to 2017 was conducted. The results of optimization of pathogenetic therapy of severe forms of falciparum malaria for the prevention of adverse outcomes in the intensive care unit of the Infectious Clinical Hospital №2 of Moscow in 44 patients with severe course are presented. Treatment, clinical laboratory and instrumental investigations were carried out in accordance with our intensive care protocol, which took into account the current WHO recommendations. RESULTS: From 2013 to 2017 there were nine deaths from falciparum malaria reported in patients from African countries (6) and India (3). In Russia, due to the lack of effective drugs of artemisinin group, quinine with tetracycline or doxycycline is used for etiotropic therapy of patients with complicated form of falciparum malaria. In the management of such patients, the basis for treatment was the prevention of ischemic, reperfusion injuries of organs and hemorrhagic complications. In the infectious clinical hospital №2 of Moscow, since 2007, the intensive care unit has developed and tested a protocol for intensive therapy in patients with severe and complicated forms of falciparum malaria, including preventive methods of extracorporeal hemocorrection with prolonged veno-venous hemodiafiltration therapy and plasmapheresis, as a result of which the mortality rate decreased from 84 to 6.8. CONCLUSION: The country's lack of anti-malarial drugs, the insufficient awareness of the population about the risk of infection and measures to prevent malaria, late referral of cases for medical care and errors of clinical diagnosis and treatment annually lead to fatal outcomes. In such situation, the experience of optimizing the treatment of severe falciparum malaria is particularly useful, allowing decreasing the mortality.

[Effect of Type 2 Diabetes Mellitus on Five­Year Survival of Patients Hospitalized Because of Acute Decompensated Heart Failure].

OBJECTIVE: To assess the impact of type 2 diabetes mellitus (T2DM) on prognosis of patients hospitalized because of acute decompensated heart failure (ADHF). MATERIALS AND METHODS: We analyzed data of the hospital register of ADHF which comprised information on 735 patients (254 [35%] with T2DM) consecutively admitted in 2010-2011. Median follow­up was 1790 days. RESULTS: The presence of T2DM was associated with increased risk of death: during the index hospitalization due to ADHF (hazard ratio [HR] 1.7, 95% confidence interval [CI] 1.0-2.8), within 18 months (HR 1.4, 95% CI 1.0-1.8), and within 5 years (HR 1.3, 95% CI 1.0-1.5). CONCLUSIONS: T2DM is common among acute decompensated heart failure patients (up to 35% of cases). T2DM is an independent risk factor of death during the index hospitalization and over the next 18 months and 5 years.

[(INDUCED MALARIA)].

Induced malaria continues to be one of the most pressing public health problems in malaria-endemic countries. Ma- laria parasites remain viable in stored blood at a temperature of 2-6°C for 3 weeks. The paper presents current problems associated with transfusion-induced malaria. In the USSR and then in the Russian Federation, sporadic cases of induced malaria (Plasniodium vivax, P.malariae, rarely P.falciparum) were notified (230 cases in 1958 to 1990 and only 5 in 1991 to 2016). Current (immunological and molecular) methods for the laboratory diagnosis of malaria do not provide a 100% detection rMfteor its pathogens; therefore, it is necessary to search for highly efficient, rapid, and low-cost diagnostic methods to ensure the biological safety of donation.

[(THE IMPACT OF MIGRATION PROCESSES ON- BIOSAFETY AND HUMAN HEALTH)].

Infectious diseases are one of the serious threats to biosafety in modern society In recent years, there have been con- siderably increased international migrations: tourism and pilgrimage; labor migration flows; migration of refugees and settlers in times of armed conflicts, household migrations because of family ties and traditions. Since the number of Rus- sian tourists and migrants from endemic countries remains high, these contingents should receive special attention in the malaria epidemiological surveillance system. The paper discusses the risks of possible consequences of population migra- tions and prevention measures.

[(INTRODUCTION OF RESEARCH RESULTS INTO THE TRAINING OF PHYSICIANS IN THE SPECIALTY OF PARASITOLOGY)].

The paper presents the results of theoretical and practical studies into parasitology, which were conducted at the E.I.Martsinovsky Institute of Medical Parasitology, Tropical and Vector-Borne Diseases and then used for the training of specialists with higher medical education at the Department of Tropical Medicine and Parasitic Diseases, I.M.Sechenov First Moscow State Medical University. The need to develop professional skills is related to the increasing learning require- ments due to socioeconomic conditions and the epidemiological situation in the country.

[(EXPERIENCE WITH GEOGRAPHIC INFORRMATION SYSTEMS USED IN EPIDEMIOLOGICAL STUDIES (AS AN EXAMPLE OF MALARIA AND DIROFILARIASIS)].

The effective application of GIS against parasitic diseases requires the patterns of spread of parasitic diseases in certain natural, climatic, and socioeconomic conditions of different regions where there are epidemically effective carriers. The epidemiological parameters defining a high risk of an epidemiological process after P.vivax importation into Russia were calculated using the developed HealthMapper controlled module with a database. Analysis of the average long-term air temperatures in the administrative territories of Russia over 78 years, namely July, the warmest month of the year when there are the largest numbers of all types of mosquito vectors and high levels of microfilaria in the peripheral blood of in- fected dogs (definitive hosts), has shown that the northern border of the maximum possible area of dirofilariasis in Russia is most fully described by the +14C July isotherm.

[MALARIA IMPORTATION BY RUSSIA'S CITIZENS AND FOREIGNERS, INTO THE CITIES AND TOWNS OF THE RUSSIAN FEDERATION].

A total of 436 malaria cases, including 12 from the CIS countries and 424 from far foreign countries (of Africa and Central and South-East Asia), were imported into the Russian Federation in 2010-2014. Most (96.6%) cases were notified in the urban areas of 52 administrative subjects of Russia. The largest number of the imported cases were seasonal workers (39.2%), tourists (31.3%), students and foreign postgraduate students (19.5%), and ship or aircraft crews (10%). During a short malaria transmission season (June to August), there were 150 cases of different types, out of them there were only 63 cases of tertian malaria (its pathogen is Plasmodium vivax, to which malaria mosquitoes of Russia's fauna are susceptible). The relatively small number of infection sources in the short transmission (June to August) season of malaria, its importation into low-susceptibility large towns, and a small proportion of imported vivax malaria cases substantially reduce the risk of malaria in the highrisk areas of the country.

[The Mechanisms of Transgenerational Inheritance and Their Potential Contribution to Human Phenotypes].

As of today, classical genetics has already completed the majority of groundwork to describe the laws of inheritance, identify the causes of many human diseases, and dissect the mechanisms of transfer of genetic information from parents to offspring. However, recent studies indicate that inheritance of phenotypic traits may also occur through nongenetic factors, in particular, through epigenetic factors, that manifest their effects in a transgenerational fashion. This review discusses findings in the area of transgenerational inheritance that open a new era in modern genetics. We discuss the mechanisms of transgenerational inheritance, including DNA methylation, histone modifications, and noncoding RNA transfer, and give an overview of the approaches to detect transgenerational effects in humans.

SCIENTIFIC AND PRACTICAL STUDIES OF MALARIA IN THE CIS COUNTRIES AND GEORGIA.

The paper presents the scientific studies of malaria pathogens and vectors, which have been specially conducted in the endemic areas of the CIS countries and Georgia for use in an epidemiological surveillance system. The main ones investigate the structure of malaria foci and the level of G-6-PD deficiency among residents, determine the malariogenic potential. of the territory and the risk of infection in the population, and specify the taxonomy, systematics, and spread of major malaria vectors in .the countries ofWHO European Region. In addition, the time and magnitude of manifestations of long-term post-incubation tertian malaria were established; th6 susceptibility of P.vivax to antimalarials and the levels of resistance and irritability of malaria vectors to insecticides were studied. The experience in using a geographic information system for the epidemiological surveillance of malaria is given.