[Comparative analysis of clinical and functional parameters in patients with stable stage II-III keratoconus after implantation of corneal segments and fitting of scleral rigid contact lenses]. / Sravnitel'nyi analiz kliniko-funktsional'nykh pokazatelei u patsientov so stabil'nym keratokonusom II­III stadii posle implantatsii rogovichnykh segmentov i podbora skleral'nykh zhestkikh kontaktnykh linz.

The modern treatment strategy for keratoconus (KC) involves sequential application of medical technologies aimed at stabilizing pathological changes in the cornea and restoring visual acuity. PURPOSE: This study compares the effect of implantation of intrastromal corneal ring segment (ICRS) and fitting of individual scleral rigid contact lenses (RCLs) on visual functions in patients with stage II-III KC after previously performed corneal collagen cross-linking. MATERIAL AND METHODS: The Helmholtz National Medical Research Center of Eye Diseases examined and treated 34 patients (69 eyes) aged 18 to 33 years with stage II-III KC. The study included patients who had previously undergone standard corneal collagen cross-linking. Depending on the type of optical correction, the patients were divided into two groups: patients in group 1 underwent ICRS implantation using a femtosecond laser; patients in group 2 were fitted with individual scleral RCLs. RESULTS: Improvement in clinical and functional parameters was observed in both groups. A higher clinical and functional result was achieved in group 2. CONCLUSION: For patients with stable stage II-III KC, it is advisable to recommend fitting of individual scleral RCLs for visual rehabilitation.

[Transplantation of the Bowman's layer in combined treatment of recurrent pterygium]. / Transplantatsiya boumenova sloya v kombinirovannom lechenii retsidiviruyushchego pterigiuma.

Pterygium is among the most frequent indications for extraocular ophthalmic surgery. The main method of pterygium treatment - its excision - is often combined with transplantation, non-transplantation, medication and other methods. However, the frequency of pterygium recurrence can exceed 35%, and the cosmetic and refraction outcomes satisfy neither the patient, nor the surgeon. PURPOSE: The study analyses the technical capability and feasibility for transplantation of the Bowman's layer in the treatment of recurrent pterygium. MATERIAL AND METHODS: The transplantation of the Bowmen's layer was performed according to the developed technique on 7 eyes with recurrent pterygium (7 patients aged 34 to 63 years). The combined surgery technique consisted of pterygium resection, laser ablation, autoconjunctival plasty, exposure to a cytostatic drug, non-suture transplantation of the Bowman's layer. Maximum length of the follow-up was 36 months. Analysis involved data from refractometry, visometry (without correction and with spectacle correction), and optical coherence tomography of the retina. RESULTS: There were no complications in any of the studied cases. The cornea and the transplant retained transparency throughout the entire follow-up duration. 36 months after surgery mean spectacle-corrected visual acuity amounted to 0.86±0.2, topographic astigmatism - 1.48±1.4 diopters. Recurrence of pterygium was not observed. All patients were satisfied with the cosmetic outcomes of the treatment. CONCLUSION: Non-suture transplantation of the Bowmen's layer recovers normal anatomy, physiology and transparency of the cornea after repeat surgical intervention for pterygium. No pterygium recurrences were observed throughout the entire follow-up after treatment with the proposed combined technique.

Prototype of a DNA Vaccine against Marburg Virus.

The preparation and study of the biological properties of the pVAKS-GPVM DNA immunogen containing a gene encoding Marburgvirus glycoprotein are described. The specificity of blood serum antibodies of guinea pigs immunized with DNA immunogen was analyzed by ELISA. Inactivated viral preparation, recombinant glycoprotein (GP) obtained in the prokaryotic system and virus-like particles based on the recombinant vesicular stomatitis virus exhibiting Marburgvirus GP were used as the antigens. The neutralizing activity of antibodies of immunized animals was tested in vitro using a pseudovirus system. It was demonstrated that the developed immunogen administered to guinea pigs induced the production of specific antibodies that neutralize virus-like particles and Marburgvirus in cultured Vero cells.

[Myocardial infarction in a patient with a single ventricle of the heart].

A clinical case of myocardial infarction in a patient with single ventricle heart defect is described.

[Experimental study of the effect of corneal hydration and its biomechanical properties on the results of photorefractive keratectomy]. / Vliyanie gidratatsii i biomekhanicheskikh svoistv rogovitsy na rezul'taty fotorefraktsionnoi keratektomii v eksperimente.

Water content in the cornea may affect the outcome of its excimer laser ablation, especially in presbyopic patients with myopic refraction. This hypothesis can be tested by scanning the cornea in the terahertz (THz) range to determine its hydration level. PURPOSE: To study the effect of hydration of the cornea determined by non-contact THz scanning and its biomechanical parameters on the results of photorefractive keratectomy (PRK) in an experiment. MATERIAL AND METHODS: PRK was performed using the Nidek EC-5000 QUEST excimer laser on 8 rabbit eyes. Corneal hydration was evaluated by determining the reflection coefficient (RC) in the THz electromagnetic radiation range before PRK, after 3-5 days, and after 1, 2, 3, and 4 months. Clinical examination included autorefractometry, assessment of corneal thickness and other anatomical and optical parameters of the anterior eye segment (Galilei G6, Ziemer Ophthalmic Systems AG 6.0.2, Switzerland), measurement of corneal hysteresis (CH) and corneal resistance factor (CRF) using the Ocular Response Analyzer (ORA; Reichert, USA), as well as tear production (Schirmer test). RESULTS: The initial water content in the cornea has a significant effect on the thickness of the removed layer, i.e. on the PRK effect, with correlation coefficient of Rs= -0.976 (p<0.01). The correlation between CH and the ablation depth is less pronounced (Rs=0.643), and CRF had no correlation with it (Rs= -0.089). Biomechanical indicators of the cornea depend on its hydration: changes in CH and CRF after excimer laser ablation qualitatively coincide with changes in RC, the correlation coefficient between RC and the initial value of CH is R= -0.619 (moderate negative correlation). CONCLUSION: THz scanning is an effective non-contact technology for monitoring corneal hydration level. The mismatch of the hypoeffect of keratorefractive excimer laser intervention planned for patients with presbyopia with the actual outcome can be caused by individual decrease in the initial water content in the cornea.

Synthesis and biological evaluation of 6-nitro-1,2,4-triazoloazines containing polyphenol fragments possessing antioxidant and antiviral activity.

Stable σ-adducts of azolo[5,1-c]triazines and azolo[1,5-a]pyrimidines with different polyphenols were synthesized and their antioxidant and antiviral activity were investigated. Their affinity to viral hemagglutinin was assessed using molecular modelling. The phloroglucinol-modified azolo-azines possessed the highest virus-inhibiting activity. According to the results of the study of antioxidant properties of compounds, the most promising ones exhibiting highest antioxidant capacity were adducts containing in their structure pyrogallol and catechol residues and 6-nitro-triazolotriazin-7-ol scaffold. No correlation between antioxidant and virus-inhibiting activity of compounds studied was detected. The most active compounds demonstrated the ability to prevent binding of viral hemagglutinin with cellular receptor as shown in hemagglutination inhibition assay. Our results demonstrate that polyphenol-modified azolo-azines are prospective for further optimization as potential antivirals and that their action is directed against viral hemagglutinin.

Synthesis and Metabolism of Nitric Oxide (NO) in Chicken Embryos and in the Blood of Adult Chicken.

In chicken embryos, nitric oxide (NO) is accumulated in the pool of NO donors: S-nitrosothiols, nitrosyl-iron complexes, high-molecular-weight nitro-compounds. Oxidation of NO to nitrate occurs with different intensity in the embryos of different chicken breeds. In some embryos, NO donors accumulate almost without oxidation. Stable concentration of NO donors and nitrate in the blood of adult chicken is a result of dynamic equilibrium between NO synthesis and elimination (oxidation, consumption by other tissues, and excretion). As NO oxidation occurs mainly not in the blood, but in other tissues, decomposition of NO donors and NO oxidation are determined the properties of these tissues, in particular, the presence of physiological targets of NO, rather than spontaneous processes. Hence, evaluation of the intensity of NO metabolism is important for prediction of the efficiency of preparations containing NO donors and stimulators of its synthesis.

First Experience of Sutureless Redo on Mitral Valve Using Valve-in-Valve Technique: Two-Stage Implantation on a Large Animal.

Sutureless implantation of the mitral valve bioprosthesis using the valve-in-valve method was performed on a large animal (sheep). According to the results of a two-stage implantation (primary implantation of a xenopericardial 26-mm framed bioprosthesis and reimplantation of the developed 23-mm bioprosthesis), minor changes in quantitative indicators were revealed: an increase in the transprosthetic gradient by 1.3 mm Hg and a decrease in the area of the mitral orifice by 21.6%. Considerable reduction in the intervention time by 18 min was achieved (by 40% in comparison with the primary prosthesis). The absence of adverse events in the animal and complications in the post-operative period, as well as physiological hemodynamic indicators indicate the safety of the developed medical device.

[Dynamics of Parameters of Transmitral Blood Flow and Markers of Myocardial Fibrosis in Patients with Myocardial Infarction].

Aim      To study possible correlations between echocardiography (EchoCG) indexes and markers of myocardial fibrosis, procollagen I C-terminal propeptide (PICP) and procollagen III N-terminal propeptide (PIIINP) during one year following ST-segment elevation myocardial infarction (STEMI).Material and methods  120 patients with STEMI were evaluated. EchoCG was used to assess dimensions and volumes of heart chambers, left ventricular (LV) systolic function, mean pulmonary arterial pressure (mPAP), and indexes of LV diastolic function (Em, early diastolic lateral mitral annular velocity; e', peak early diastolic septal mitral annular velocity; E / e', ratio of peak early diastolic transmitral inflow velocity and mitral annular velocity  -, Е / А, ratio of peak early and late transmitral inflow velocities; DT, deceleration time of LV early diastolic filling). EchoCG indexes and serum concentrations of PICP and PIIINP were determined at 1 (point 1) and 12 (point 2) days of disease and one year after STEMI (point 3). The sample was divided into two groups: group 1 (n=86; 71.7 %) included patients with a LV ejection fraction (EF) ≥50 % and group 2 (n=34; 28.3 %) consisted of patients with LV EF ≤49 %.Results At one year, the number of patients with signs of diastolic dysfunction increased by 10% in group 1 whereas myocardial systolic dysfunction worsened in both groups. LV EF decreased in 15 (17.4%) patients of group 1 and in 4 (11.8%) patients of group 2. Concentrations of PIIINP were correlated with Em, E / e', mPAP, PICP, e', and LV EF.Conclusion      Direct correlations between PIIINP concentrations and Em, E / e', and mPAP were found in the group with LV EF ≥50 %. In the group with LV EF <50 %, correlations were observed between PICP concentrations, LV EF, and e'. Also, in this group, the increase in PIIINP was statistically more significant. These results indicate continuing formation of myocardial fibrosis in a year following MI, which may underlie progression of chronic heart failure.

[REVIEW OF EPIDEMIOLOGIC SITUATION ON HEMORRHAGIC FEVER WITH RENAL SYNDROME (HERS) IN RUSSIAN FEDERATION IN 1990 - 2015].

AIM: Analyze HFRS morbidity in Russian Federation during the last 25 years (1990 - 2015). MATERIALS AND METHODS: Official statistics of Federal Service for Surveillance on Consumers' Rights Protection and Human Weillbeing (CPS), including Federal Centre of Hygiene and Epidemiology, were used for the analysis, as well as materials from regional departments of CPS and centers of hygiene and epidemiology. Epidemiologic analysis was the main method. Statistical treatment of the results obtained was carried out using gener- ally accepted methods of variation statistics with elements of system analysis. Results; For the studied period (1990 - 2015) 194 116 cases of HFRS were registered. Morbidity was registered in 8 federal districts of the Russian Federation in 58 subjects. The most intense epidemiologic situation was noted in Privolzhsky Federal District, that accounted for 86.4% of total HFRS morbidity during the -studied period. Analysis of morbidity was carried out in every federal district, most epidemically unfavorable territories are shown. CONCLUSION: The data presented on HFRS morbidity reflect -unfavorable situation for this disease in Russian Federation. Measures to prevent the emergence of diseases to reduce the general level of morbidity in Russian Federation are presented.

The Habituation/Cross-Habituation Test Revisited: Guidance from Sniffing and Video Tracking.

The habituation/cross-habituation test (HaXha) is a spontaneous odor discrimination task that has been used for many decades to evaluate olfactory function in animals. Animals are presented repeatedly with the same odorant after which a new odorant is introduced. The time the animal explores the odor object is measured. An animal is considered to cross-habituate during the novel stimulus trial when the exploration time is higher than the prior trial and indicates the degree of olfactory patency. On the other hand, habituation across the repeated trials involves decreased exploration time and is related to memory patency, especially at long intervals. Classically exploration is timed using a stopwatch when the animal is within 2 cm of the object and aimed toward it. These criteria are intuitive, but it is unclear how they relate to olfactory exploration, that is, sniffing. We used video tracking combined with plethysmography to improve accuracy, avoid observer bias, and propose more robust criteria for exploratory scoring when sniff measures are not available. We also demonstrate that sniff rate combined with proximity is the most direct measure of odorant exploration and provide a robust and sensitive criterion.

[Clinical Case of Severe Heart Failure Treatment, Produced due to the Development of Arrhythmogenic Cardiomyopathy in a Patient With Permanent Junctional Reciprocating Tachycardia (Coumels Tachycardia) With Additional Left Lateral Accessory Pathway].

Thirty two years old man had history of atrioventricular re-entry tachycardia (AVRT) with concealed left-lateral accessory pathway (AP), 3-5episodes per year, 30-40 minutes duration without hemodynamic compromise. Two years ago patient underwent ablation of concealed left lateral AP. After that tachycardia became malignant (high-frequent 150 beats-min, incessant (lasting up to 18 h/day), resistant to AAD, and led to development of tachycardia-induced cardiomyopathy (EF was 16%, and 2 episodes of pulmonary oedema). During redo EPS we verified AVRT with conduction via decremental retrograde left lateral AP which corresponded to the criteria of permanent junctional reciprocating tachycardia (PJRT). Ablation effectively ceased the arrhythmia. After 18 months of follow up there are no symptoms of heart failure and recurrence of arrhythmia. CONCLUSIONS: We present a case of effective treatment of severe heart failure in a patient with arhythtmogenic cardiomyopathy due to malignant course of incessant tachycardia AVRT with retrograde decremental conduction via left lateral AP. Ablation of AP eliminated of arrhythmia. After 18 months of follow up patient had signs of left ventricle reverse remodeling and had not heart failure symptoms.

[Receptor tyrosine kinase KIT may regulate expression of genes involved in spontaneous regression of neuroblastoma].

Hallmark of neuroblastoma is an ability of this malignant tumor to undergo spontaneous regression or differentiation into benign tumor during any stage of the disease, but it is little known about mechanisms of these phenomena. We studied effect of receptor tyrosine kinase receptor KIT on expression of genes, which may be involved in tumor spontaneous regression. Downregulation of KIT expression by RNA interference in SH-SY5Y cells causes suppression of neurotrophin receptor NGFR expression that may promote the loss of sensibility of cells to nerve growth factors, also it causes upregulation of TrkA receptor expression which can stimulate cell differentiation or apoptosis in NGF dependent manner. Furthermore there is an upregulation of genes which stimulate malignant cell detection by immune system, such as genes of major histocompatibility complex HLA class I HLA-B and HLA-C, and interferon-γ receptors IFNGR1 and IFNGR2 genes. Thus KIT can mediate neuroblastoma cell sensibility to neurotrophins and immune system components--two factors directly contributing to spontaneous regression of neuroblastoma.

Specific role of nitric oxide (NO) in avian embryonic myogenesis.

NO plays a specific role in avian embryogenesis stimulating the development of muscle tissue. The main consumer of NO synthesized at the initial stage of avian embryogenesis is presumably a factor stimulating myogenesis.

[Elastogenesis-Related Gene Polymorphisms and the Risk of Pelvic Organ Prolapse Development].

Pelvic organ prolapse (POP) represents a urologic and gynecological disease, the development of which is governed both by environmental and genetic factors. We describe the results of our association study of polymorphic variants of genes involved in the assembly of elastic fibrils, namely, the lysyl oxidase protein 1 (LOXL1) and fibulin-3 (FBLN3) genes. We revealed an association of the rs2304719-T allele and rs2165241 (C)-rs2304719(T)-rs893821(T) haplotype of the LOXL1 gene with an increased risk of POP development, as well as a weak association with the disease of the rs3791660-C allele and the rs3791679(T)- rs1367228(A)-rs3791660(C)-rs2033316(A) haplotype of the FBLN3 gene.

Effect of Green Light on Nitric Oxide Metabolism in Chick Embryos. A Possible Physiological Role.

The exposure to green light, which serves as a well-known activating factor for myogenesis during incubation of chicken eggs, contributes to intensification of embryonic metabolism of NO. A metabolic product, nitrate, is mainly accumulated in the muscles. These data suggest that light induces a NO-dependent activation of the factor, which intensifies muscle tissue development.

[OPTIMIZATION OF EARLY DIAGNOSIS OF ACUTE KIDNEY INJURY IN NEWBORNS IN CRITICAL CONDITION].

UNLABELLED: Current diagnosis of acute kidney injury (AKI) is one of the most pressing problems in the newborn in critical condition. OBJECTIVE: To determine the diagnostic value of indicators of renal blood flow as a marker of acute kidney injury in critically ill newborns. MATERIALS AND METHODS: The study included 40 infants in critical condition. A clinical assessment of severity of the condition during admission was carried out with Neonatal Multiple Organ Dysfunction Score (NEOMOD) and Neonatal Therapeutic Intervention Scoring System (NTISS). All patients underwent evaluation of clinical and instrumental parameters, including ultrasound of the renal vessels, renal vascular resistance index and speed performance. CONCLUSIONS: 1) biochemical markers used in routine clinical practice were not sufficiently informative for the diagnosis of AKI. 2) For a more accurate assessment of the risk of AKI using serum creatinine, GFR calculation and evaluation on a scale RIFLE it is should be focused on performance standards, appropriate for gestational age and birth weight. 3) Evaluation of blood flow at a particular index in the resistance of the main renal arteries had the greatest predictive value and had a relatively high sensitivity and specificity for the diagnosis of AKI.

Possible mechanism of generation of nitrite and non-thiolate nitroso compounds in blood plasma during inflammatory processes.

Generation of nitrite (NO2¯) and non-thiolate nitroso compounds in human blood during leukocyte activation mainly occurred due to destruction of NO donors in the plasma, but not due to intensification of NO synthesis. We proposed a mechanism of production of nitrite and non-thiolate nitroso compounds in the blood during inflammation.

The chromo and SET domains of the Clr4 protein are essential for silencing in fission yeast.

Heritable inactivation of specific regions of the genome is a widespread, possibly universal phenomenon for gene regulation in eukaryotes. Self-perpetuating, clonally inherited chromatin structure has been proposed as the explanation for such phenomena as position-effect variegation (PEV) and control of segment determination and differentiation in flies, X-chromosome inactivation and parental imprinting in mammals, gene silencing by paramutation in maize and silencing of the mating-type loci in yeasts. We have now found that the clr4 gene, which is essential for silencing of centromeres and the mating-type loci in Schizosaccharomyces pombe, encodes a protein with high homology to the product of Su(var)3-9, a gene affecting PEV in Drosophila. Like Su(var)3-9p, Clr4p contains SET and chromo domains, motifs found in proteins that modulate chromatin structure. Site-directed mutations in the conserved residues of the chromo domain confirm that it is required for proper silencing and directional switching of the mating type, like SET domain. Surprisingly, RNA differential display experiments demonstrated that clr4+ can mediate transcriptional activation of certain other loci. These results show that clr4 plays a critical role in silencing at mating-type loci and centromeres through the organization of repressive chromatin structure and demonstrate a new, activator function for Clr4p.

Can summary nitrite+nitrate content serve as an indicator of NO synthesis intensity in body tissues?

Studies with the use of a highly specific enzymatic sensor demonstrated that, contrary to the common opinion, normally nitrate is in fact not present in the most important physiological fluids. NO metabolites in the amniotic fluid and semen are mainly presented by NO donor compounds. Therefore, the intensity of NO synthesis can be evaluated by the total content of all its metabolites, but not by the widely used summary nitrite+nitrate content.