[Episcleral circular buckling in surgical treatment of recurrent rhegmatogenous retinal detachment after vitrectomy]. / Episkleral'noe krugovoe plombirovanie v khirurgii retsidivov regmatogennoi otsloiki setchatki na avitreal'nykh glazakh.

Despite the improvement of the surgical technique of vitreoretinal interventions, the number of recurrences of rhegmatogenous retinal detachment (RRD) remains quite high. PURPOSE: Evaluation of the effectiveness of episcleral circular buckling (ECB) in the treatment of recurrent RRD after vitrectomy due to progression of proliferative vitreoretinopathy (PVR). MATERIAL AND METHODS: The study analyzed the results of surgical treatment of 21 patients (21 eyes) with recurrent RRD after primary vitrectomy. All patients underwent standard preoperative examination including visometry, tonometry, ophthalmobiomicroscopy, and additionally, optical coherence tomography was performed to assess the involvement of the macular area; the presence of anterior proliferative vitreoretinopathy was determined by ultrasound biomicroscopy, axial eye length was measured with an optical biometer. All patients underwent ECB, in some cases combined with repeated vitreoretinal surgery. RESULTS: Preliminary results of the study showed high efficiency of ECB exclusively, as well as ECB combined with revision of the vitreal cavity in case of RRD recurrence after primary vitreoretinal surgery, which amounted to 95% after one additional operation and removal of silicone oil. CONCLUSIONS: Episcleral circular buckling in the treatment of recurrent RRD after vitreoretinal surgery is a multifunctional and safe method that allows achieving favorable functional and anatomical outcomes.

[Modern aspects of the treatment of submacular hemorrhages secondary to macular degeneration]. / Sovremennye aspekty terapii submakulyarnykh krovoizliyanii na fone makulyarnoi degeneratsii.

Age-related macular degeneration complicated by submacular hemorrhage if not treated timely leads to permanent loss of central vision. The basis of effective therapy is its early start, dislocation of blood from central parts of the retina and blockage of neovascularization. This review examines the current methods of treatment of submacular hemorrhages, anatomical and functional outcomes, risks of postoperative complications, as well as trends in the use of combined methods of surgical intervention.

Comparative study of the serum hepcidin level of patients with pneumonia in COVID-19 and Pneumocystis pneumonia.

In the context of a pandemic caused by the SARS-CoV-2 virus, for a patient with respiratory symptoms and bilateral lung damage, COVID-19 becomes the first disease in the differential diagnostic search. Pneumonia in COVID-19 shares many characteristics with Pneumocystis pneumonia. One of the possible markers of the severe course of COVID-19 is hepcidin, a peptide hormone that negatively regulates iron metabolism. There are no data on the value of hepcidin in Pneumocystis pneumonia in the published scientific literature. The purpose of this study is to conduct a comparative analysis of hepcidin in the blood serum of patients with pneumonia in COVID-19 and Pneumocystis pneumonia to clarify their pathogenetic features. A case-control observational study was conducted, including 68 patients with pneumonia in COVID-19 and 44 patients with HIV infection and Pneumocystis pneumonia (PCP/HIV). Determination of hepcidin was carried out by ELISA using the ELISA Kit for Hepcidin. Statistical data processing was carried out using the MedCalc 19.2.6 software. Results. Comparative analysis of serum hepcidin levels in the study groups showed that hepcidin is statistically significantly higher in PCP/HIV than in COVID-19 - the median value is 22 times higher (p <0.0001). When examining the ROC curve for hepcidin, it was found that this biomarker has a high diagnostic potential and indicates a higher probability of COVID-19 than PCP/HIV at values ≤768.044 pg / ml. In the context of the COVID-19 pandemic, it is necessary to remember about other diseases that manifest themselves with a similar clinical and radiological picture. COVID-19 and PCP/HIV share many similarities; the peptide hormone hepcidin has shown itself as a potential differential diagnostic marker between them, and therefore the need for further studies of hepcidin is justified, taking into account the severity of the course of COVID-19, the presence of comorbidities and in a comparative aspect with pathologies that «mimic¼ under COVID-19.

[Anti-VEGF therapy for diabetic retinopathy]. / Anti-VEGF preparaty v lechenii diabeticheskoi retinopatii.

Diabetic retinopathy (DR) is one of the most severe complications of diabetes mellitus, its treatment involves specialists of different areas - endocrinologists, diabetes specialists, therapists, cardiologists, surgeons, anesthesiologists etc. For ophthalmologists the objective is to diagnose ocular pathological changes associated with diabetes mellitus, and to prescribe required treatment in a timely manner. Treatment methods used in DR can be divided into three main groups: laser coagulation of the retina, intravitreal injection of medications - inhibitors of the vascular endothelial growth factor (VEGF) and glucocorticoids, as well as surgical treatment. The present literature review addresses the use of anti-VEGF drugs in the therapy of DR, specifically the latest medications, the most important studies on the treatment of DR and diabetic macular edema (DME), as well as post hoc analysis of such studies, the role of these medications in the therapy of refractory DME and proliferative stage DR. The review also addresses the upcoming strategies for therapy, as well as the importance of medications in prevention of DR and DME.

[Antiangiogenic therapy of neovascular age-related macular degeneration]. / Antiangiogennaya terapiya neovaskulyarnoi vozrastnoi makulyarnoi degeneratsii.

The problem associated with the prevalence of retinal diseases, and age-related macular degeneration (AMD) in particular, is undoubtedly relevant. This aspect is based on steadily growing statistics on morbidity, a high number of randomized controlled trials (RCT) and published real world data (RWD). The analysis of RCT results being published by researchers on 15.05.19 showed 2915 studies were registered on the subject of retinal diseases; that exceeds the number of studies on glaucoma by approximately 1.38 times (2118 studies) and conjunctival lesions by 2.37 times (1230 studies). AMD is one of the leading causes of irreversible vision loss and blindness; its neovascular form leads to blindness in 80-90% of all cases. Even though the topic of nAMD therapy is widely highlighted in modern ophthalmology, today there are many aspects that require targeted solutions. The main controversial issues that determine the complexity of therapy and patient management include discrepancies in determination of reference points (disease activity criteria) for implementation of anti-VEGF dosing regimens, patients' compliance, prioritization issues in treatment, its continuity with potential for the increase of intervals between injections and monitoring visits.

[Changes in perfusional and morphological parameters of the macular area after silicone oil tamponade of the vitreous cavity]. / Dinamika perfuzionnykh i morfologicheskikh parametrov makulyarnoi zony pri silikonovoi tamponade vitreal'noi polosti.

PURPOSE: To compare the changes of the macular morphological and functional parameters in the postoperative period in patients with silicone oil tamponade after successful surgery of the macula-on rhegmatogenous retinal detachment (RRD). MATERIAL AND METHODS: The study included 20 eyes operated on for macula-on RRD, which made up the first group, and the control group (20 eyes) for comparison. All patients of the study group underwent vitrectomy using silicone oil tamponade. Standard ophthalmological examination was performed on the 3rd day (early postoperative period) and the 14th day (late postoperative period), including OCT and OCT-A that were used to assess morphological and functional changes. RESULTS: A significant decrease in visual acuity was seen on the 3rd day after surgery involving the use of silicone oil tamponade, in comparison with the 14th day (p=0.0237) and the control group (p=0.0001). A decrease in the FD parameter (p=0.045), a decrease in vascular density in the fovea (p=0.020) and parafovea (p=0.024) in SCP were found on the 3rd day in comparison with control. On the 14th day of postoperative observation, a tendency was detected for choroidal perfusion to restore, as well as significant increase in FD (p=0.016), and an increase in vascular density in parafovea (p=0.01) compared with the early postoperative period. No statistically significant changes were seen in the FAZ area and vessel density DCP (p>0.05).

Poly-3-hydroxybutyrate/chitosan composite films and nonwoven mats.

Composite films and nonwoven mats of the poly-3-hydroxybutyrate and chitosan natural polymers were prepared and investigated. DSC and FTIR techniques were used to confirm that P(3HB) blending with chitosan resulted in a decrease in P(3HB) crystallinity to 47% and 62% in the films and nonwoven mats, respectively. Scanning electron microscopy showed that addition of chitosan induced changes in the surface morphology of the composite films and a reduction in the diameter of ultrafine fibers in the nonwoven mats from 800 nm to 460 nm. The values of water contact angle for films (53°) and nonwoven mats (50.6°) suggested that chitosan enhanced hydrophilic properties and moisture absorption capacity of the composite materials. On the other hand, P(3HB) showed its reinforcing ability and improved the physical/mechanical properties of chitosan. The work included studies of in vitro biodegradation of the composite specimens and their ability to maintain cell growth and attachment in NIH 3T3 fibroblast culture.

[Development and validation of methodology of quantitative determination of sibutramine in dietary supplements by high performance liquid chromatography].

Sibutramine is a highly effective drug for the treatment of obesity. In this regard, unscrupulous manufacturers can add sibutramine as a biologically active synthetic substance prohibited for use in the composition of dietary supplements. Thus, the problem associated with the illegal circulation of such dietary supplements is especially actual, given the scale of the sale of these products. The development and validation of methods for the determination of sibutramine in dietary supplements for slimming (anorexigenic action) for the purpose of quality control in order to ensure the quality of dietary supplements when introduced into civil circulation at customs and on the market. The aim of the study - to develop a method for the quantitative determination of sibutramin in dietary supplements for weight loss by high performance liquid chromatography (HPLC) and to validate it. Material and methods. For the quantitative determination of sibutramine in dietary supplements, we used an Agilent 1100 high performance liquid chromatograph with a UV-detector. The stationary phase was a chromatographic column C18 NUCLEOSIL 4.6×150 mm, particle size 5 µm. The mobile phase contained 0.05 M formate buffer pH 4.0 and acetonitrile in a ratio of 40:60 (by volume). Results and discussion. A methodology has been developed for the determination of sibutramine in dietary supplements for weight loss, which makes it possible to control the quality of dietary supplements. Based on the obtained chromatograms, the specificity was determined; the plant components did not influence the determination of sibutramine in model mixtures. The suitability of the chromatographic system was determined: the retention factor of the compound - 2.222 (more than 2.0), N - 5776 theoretical plates (more than 5000), T peak of sibutramine - 0.939 (not more than 1.5). Within the analytical area of the linearity method: R2=0.9993 (over 0.9950). ε=0.46% (does not exceed 1.5%), the confidence interval includes the value of 100%, the calculated value of the Student's criterion tcalc (2.47) was less than the tabular ttable (2.80), which proved the correctness of the methodology. The precision of the results was determined by the obtained RSD value, which was 0.91% (less than 1%). Limit of detection (LOD) and limit of quantification (LOQ) took values of 0.1 and 1.0%, respectively. The range of measured concentrations was 0.01-20.0 mg/g. Conclusion. As a result of the studies, the method for sibutramine determination in dietary supplements with anorexigenic action was tested and can be used in quality control of dietary supplements.

HIV Tat induces a prolonged MYC relocalization next to IGH in circulating B-cells.

With combined antiretroviral therapy (cART), the risk for HIV-infected individuals to develop a non-Hodgkin lymphoma is diminished. However, the incidence of Burkitt lymphoma (BL) remains strikingly elevated. Most BL present a t(8;14) chromosomal translocation which must take place at a time of spatial proximity between the translocation partners. The two partner genes, MYC and IGH, were found colocalized only very rarely in the nuclei of normal peripheral blood B-cells examined using 3D-FISH while circulating B-cells from HIV-infected individuals whose exhibited consistently elevated levels of MYC-IGH colocalization. In vitro, incubating normal B-cells from healthy donors with a transcriptionally active form of the HIV-encoded Tat protein rapidly activated transcription of the nuclease-encoding RAG1 gene. This created DNA damage, including in the MYC gene locus which then moved towards the center of the nucleus where it sustainably colocalized with IGH up to 10-fold more frequently than in controls. In vivo, this could be sufficient to account for the elevated risk of BL-specific chromosomal translocations which would occur following DNA double strand breaks triggered by AID in secondary lymph nodes at the final stage of immunoglobulin gene maturation. New therapeutic attitudes can be envisioned to prevent BL in this high risk group.

Detection of trace processes in the networks of neurons cultured on microelectrode arrays.

We compared the effects of electrical stimulation of primary dissociated neuronal cultures cultured on microelectrode arrays in terms on the expression of c-fos transcriptional factor that is involved in plastic reorganization in neurons. Dissociated hippocampal neurons cultured on multielectrode arrays were exposed to two stimulation protocols: high-frequency and low-frequency stimulations. Expression of c-fos was evaluated using immunofluorescence. Both high-frequency and low-frequency stimulations significantly increased c-fos expression in comparison with non-stimulated control. These findings indicate that c-fos expression can be induced in neuronal cell culture by different types of electrical stimulations and can be used for studying plasticity processes in microphysiological in vitro systems.

[The molecular epidemiological aspects of hiv-infection spreading in Perm region].

Retrospective analysis of HIV-infection spreading in Perm region in conjunction with the genetic characterization of viral subtypes circulated on this territory from 1988 (when 1st case of infection was detected) until 2005 was performed. Analysis of epidemic process allowed to determine three periods of its development basing on both epidemic intensity and nature of circulating HIV-1 subtypes. During 1988 - 1996 (first period), when viral population was heterogenous (simultaneous circulation of three HIV-1 subtypes) with multiple routes of transmission, the epidemic process was characterized by low intensity. High incidence of HIV-infection among injection drug users and high homogeneity of circulated HIV-1 variants (98% of isolated variants belonged to HIV-1 subtype A with low level of genetic variability) were characteristics of the second period lasted from 1997 to 2001. Decrease in HIV-infection incidence in 2002-2005 was accompanied by the increase of HIV-1 transmission through heterosexual contacts and continuation of subtype A predominance between isolates. However increase in heterogeneity of viral population during this period, which manifested as increase of env and pol genes polymorphism, was detected.

Irradiation of cryogenic temperature sensors by gamma dose of 1 MGy.

This article presents results of investigations of the cryogenic thermometers which can operate under high radiation environment. To clarify the temperature shifts due to gamma irradiation up to 1 MGy, the platinum (two types), carbon-glass, and TVO temperature sensors have been tested. Before the irradiation run, the selected sensors were calibrated and a series of experiments was carried out under irradiation of the sensors at 77.3 and 293 K when their readings were taken in situ. Afterwards, the postirradiation evolution (short and long time) of the sensors was measured at 4.2, 77.3, and 293 K. The results, depending on the type of the sensor, can be optimistic or pessimistic. Some comparisons with analogous data for fast neutron treatment have also been made.

[Molecular and epidemiological characterization of HIV-infection in the Altai Territory].

The genetic analysis of the variants of HIV, type 1, circulating in the Altai Territory was made. The results obtained with the use of the serological analysis and the method of the comparative evaluation of the electrophoretic mobility of heteroduplexes demonstrated that almost all analyzed samples (98.3%) belonged to subtype A. Genetic differences between these viruses did not exceed 9.20%. Moreover, 86.8% of them contained mutation V771 in the protease-coding area. Thus, HIV of subtype A, characteristic of CIS countries and containing mutation V771, may be regarded as the dominating viruses in the Altai Territory and not the viruses of subtypes B, C or A/E, typical of comparatively less remote China.

[Nano-biocaptures for research and diagnostics in inflammation diseases and cancer]. / Nano-biocapteurs pour la recherche et les diagnostics des maladies inflammatoires et du cancer.

As part of the ongoing search for ways to decrease the mortality of different pathological conditions related to cancer and inflammatory diseases, nanotechnologies currently under evaluation offer potentially attractive tools for innovative methodologies for early diagnosis, new bioimaging techniques and therapeutic strategies. Nano-tools can be employed for various functions, such as the detection of lesions at very early stages of disease development, extremely precise anatomical localization, or evaluation of the efficacy of medications specifically targeted against cells and pathological tissues. We have synthesized homogeneous CdSe/ZnS (core/shell) highly fluorescent nanocrystals (NC) detectable as individual nanoparticules with a routine fluorescent microscope. These NC are at least 10-fold brighter than the best organic fluorophores and at least 1000-fold more stable against photobleaching than AlexaFluor, for example. When conjugated with proteins, DNA or with drugs, NCs may be excited with the light of any wavelength from UV through visible spectral region providing a range of fluorescence colors depending on their diameter. These properties provide excellent perspectives for high through-put multiplexing and long-term tracking of labeled precursors for days or even weeks. We present here NC applications for ultrasensitive detection of p-glycoprotein, cytokeratins, LCA, Ki67, etc. both on the cellular level and in pathological human surgical specimens.

[Protease and reverse transcriptase genetic polymorphism in HIV type 1 subtype A variants predominating in cis countries].

To define frequencies of drug resistance mutations among HIV-1 variants circulating within the territory of Russia, subtype A HIV-1 nucleotide sequences encoding protease and reverse transcriptase were analyzed. The analysis was carried out in 141 antiretroviral-naive individuals. Low frequency (less than 1%) of primary drug resistance mutations was shown. However, high frequencies of secondary mutations V77I in protease and A62V in RT (67% H 63%, respectively) linked to each other in most cases were observed. The HIV-1 isolates bearing both substitutions (MutV77I/A62V) were also characterized by the presence of several synonymous mutations, suggesting common origin for these viruses. HIV Biochip Hybridization microarray and/or Restriction fragment-length polymorphism analyses were performed to characterize gene pol polymorphism in additional 178 subtype A HIV-1 isolates. Among total 319 samples studied, Mutv77IA62V variant accounted for 56%, and was found to predominate in Russia in terms of both its geographical distribution and number of cases caused. Moreover, these viruses were prevalent in the regions known to have highest incidence of HIV-1 infection (Irkutsk, Samara, and Moscow regions). In addition, three other variants were found: viruses not containing the substitutions V77I or A62V, and variants bearing only one of them. Evolutional relationships between all four HIV-1 variants, as well as potential impact of the gene pol polymorphism on HIV-1 replicative fitness and drug resistance development are discussed.

[Development of microchips for the detection of mutations of HIV-1 variability to protease inhibitors and the usage results]. / Razrabotka biologicheskikh mikrochipov dlia vyiavleniia mutatsii ustoichivosti VICH-1 k ingibitoram proteazy i rezul'taty ikh primeneniia.

An original biochip was constructed for the detection of 34 mutations of HIV-1 resistance to protease. A technology was worked out, which is based on the hybridization of a fluorescence-labeled amplified fragment of the pol gene of the HIV-1 provirus DNA with a set of specific oligonucleotides immobilized in 3-D hydrogel pads of the biological microchip. The biochip was used to analyze 115 samples of the subtype-1 provirus HIV-1 DNA isolated from untreated IDUs and their sexual partners in 15 regions of former USSR countries. Substitution of Val/IIe in position 77 of protease (V771) is known as secondary mutation of resistance to Nelfinavir detected in 55 (47.8%) of 115 HIV-1 variations. Its first appearance was registered in a patient with HIV in April 1997 in Tver, where its carrying variant caused an HIV outbreak. It is demonstrated that the V771-substitution variant, that dominates in Moscow, caused outbreaks in Irkutsk and Yekaterinburg and spread into separate districts of Perm and Perm Region. At the same time, no V771 HIV-1 was detected in any of the HIV studied cases diagnosed before 1998 in Moldova, Ukraine and Rostov Region.

[The genetic variability of the protease-encoding region in HIV-1 A isolates and in CRF03_AB recombinants as observed in the CIS territory]. / Geneticheskaia izmenchivost' oblasti, kodiruiushchei proteazu, u izoliatov VICH-1 podtipa A i rekombinantov CRF03_AB na territorii SNG.

Protease-encoding nucleotide sequences of 27 HIV-1 variants isolated in Russia and other CIS countries from seropositive intravenous drug-users were analyzed. None of the above persons did ever take antiretroviral drugs. The nucleotide sequences were shown to belong to subtypes A and to be have a high degree of genetic homogeneity (0.00-3.23; mean--1.38 +/- 0.79). No isolates contained any primary mutations of resistance to protease inhibitors. At the same time, above one half of the isolates bore the V771 substitution, which, according to published data, is the secondary mutation of resistance that conditions a higher resistance to Nelfinavir. Moreover, the substitution was associated with 2 synonymous mutations in triplets 31 and 78, which denotes a single origin for all V771 variants.

[Variants of human immunodeficiency virus type 1, detected in Russia among those infected by the sexual route]. / Varianty virusa immunodefitsita cheloveka tipa 1, obnaruzhivaemye v Rossii sredi infitsirovannykh polovym putem.

We analyzed 52 blood samples obtained independently from among individuals, who had never practiced the intravenous administration of drugs, for the purpose of detecting the subtypes of HIV-1 that circulated during 1999-2002. The study materials were analyzed by the methods of gag/env heteroduplex mobility assay and by env gp120 C2-V3 sequencing. Four viral subtypes (A,B,C and G) and a recombinant gagA/envB were detected in subjects contaminated through heterosexual contacts. Noteworthily, HIV-1 variations of subtype A, which were found in 22 (73.3%) of 30 analyzed samples, were predominant in this risk group. An analysis of nucleotide sequences exposed a high degree of homology between the viruses, detected previously among drug-addicts, and the isolates detected by us in subjects contaminated heterosexually. However, HIV-1, subtype B, detected by us in all 16 studied cases, still continue to circulate among the males infected through homosexual contacts with men.

[Kinetics of the lactone-carboxylate transition of hybrid camptothecin-netropsin molecules]. / Kinetika lakton/karboksilatnogo perekhoda gibridnoi molekuly kamptotetsin-netropsin.

The kinetics of the hydrolysis of the lactone ring of a hybrid molecule containing the molecules of the antitumor drug camptothecin and a derivative of the antibiotic netropsines, which is highly affine and specific to the DNA A-T sequences was investigated. It was shown that intramolecular interaction significantly slows down the rate of hydrolysis but does not change the equilibrium ratio of concentrations of the lactone and carboxylate forms of the camptothecin fragment of the hybrid molecule, which corresponds to the pH value. The use of intramolecular interaction for controlling the kinetics of the lactone/carboxylate transition makes it possible to create the drugs of the camptothecin family, which preserve the biologically active lactone form under the physiological conditions for a longer time and, therefore, are more effective as anticancer agents.