Репозиторий Университета

© 2018 Russian Academy of Medical Sciences. All Rights Reserved. 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.

© 2018 Media Sphera Publishing Group. All rights reserved. The article provides review of possible mechanisms of inhibitor coagulopathies, in particular of acquired hemophilia A. This pathology is an extremely rare disease occurring in 1-2 cases in 1 million per year. In the present study we provide data for two clinical cases of hemophilia A in women. These cases had different development mechanisms, although both women have a newly discovered missense mutation His2026Arg in the VIII factor gene. The matter of main interest is the description of the disease development in the patient with an acquired idiopathic hemophilia A with a possible disease occurrence due to an asymmetric X-chromosome inactivation (lyonization). In this particular case lyonization led to the late manifestation of the hemophilia A carrier's state and development of severe form of the inhibitor-associated acquired hemophilia A. We also discuss therapeutic approaches to these forms of the disease, considering there are no concise protocols for case management due to an extreme rarity of the pathology. Acquainting the clinical personnel working it the different areas of medicine with suchlike inhibitor coagulopathies has a major practical importance.

© 2018 Dynasty Publishing House. All rights reserved. One of the most important tasks of clinical medicine is to stop bleeding as soon as possible. Despite the broad spectrum of modern haemostatic materials, the available local blood-stopping products are not without certain limitations and shortcomings when used in various clinical situations. The article discusses the potential of «Polygemostat», a Russian haemostatic for external and local use, which simultaneously has an antiseptic and wound-healing effect.

© 2018 Dynasty Publishing House. All rights reserved. Hepatocellular carcinoma (HCC) is rarely diagnosed during pregnancy, its fibrolamellar variant (FHCC) is a specific form that is more often diagnosed in young women and is rarely associated with cirrhosis or chronic infection with hepatitis B or C viruses. Making a diagnosis at early stages is complicated by the fact that the α-fetoprotein (AFP) level is usually not enhanced, and symptoms develop only at advanced stages of disease. A clinical case of FHCC in a 27-year-old woman is presented, diagnosed at the 30th week of pregnancy after persistent dragging and spastic pains in the epigastric region. US detected a tumour with sizes 110 × 81 × 89 mm and foci in the lungs. Variants of treating such patients depending on tumour characteristics, pregnancy period and family preferences are discussed.

© 2018 Russian Presidential Academy of National Economy and Public Administration. All rights reserved. This article uses oral history interviews to examine the memory of believers from Evangelical Christian-Baptist (ECB) churches regarding the requirements for women's external appearance as a reflection of their personal piety. While discussing believers' memory of the late Soviet period, the article demonstrates that these congregations focused almost exclusively on women. The conviction that believers were not to reflect the "outside world" in appearance was actually a double standard for women, since women's fashion choices have been much more dynamic than men's in the Soviet and post-Soviet periods. The article discusses the historical and social significance of the emphasis on women's appearance, arguing that both a high view of scripture and a nostalgia for the "Soviet past" perpetuated the patriarchal norms held by both men and women in ECB congregations. The authors then utilize a series of historical photographs from the 1940s to the 1970s to demonstrate the scope of the transformation of ECB believers' memory, which did not always accurately reflect late-Soviet reality. The authors conclude that the extensive changes in the social order in general and in women's fashion in particular in the post-Soviet period strengthened believers' impulse to isolate themselves from the immoral "outside world." By following the accepted norms for their external appearance, ECB women's appearance becomes a marker of their faith and a visible sign of their piety that is so highly prized by their community.

© Bionika Media Ltd. Endometriosis affects up to 15% of reproductive-aged women. Consideration of this nosological entity in a new aspect is impelled by the evidence that 0.5–1% of cases develops endometriosis-associated ovarian neoplasms that are more represented by the endometrioid and clear-cell subtypes of tumors. This category also includes seromucinous ovarian tumors (SMOTs). Objective. To investigate the morphological and immunohistochemical (IHC) features of SMOTs in reproductiveaged women, including pregnant ones. Subjects and methods. Ovarian tumor samples from 15 patients who had been operated on in 2012-2016 were analyzed comprehensively at the National Medical Research Center of Obstetrics, Gynecology, and Perinatology: IHC examination was conducted using the biomarkers of estrogen and progesterone receptors and Ki-67. Results. Borderline SMOTs were characterized by papillary growths on the inner surface (in one case) and on the outer surface, with an adhesive process with the serous surface of the corpus uteri (FIGO Stage 1c), and mixed epithelial structures; leukocyte infiltration was observed in 4 cases. The epithelium of seromucinous carcinoma (n = 1) was similar to that of serous, endocervical, and endometrial types at the same time. All the samples exhibited a low Ki-67 expression and high positive receptor immunoreactivity. Endometriosis diagnosed in nine women was accompanied by benign seromucinous cystadenomas (n = 4), borderline tumors (n = 4), and carcinoma (n = 1). Conclusion. Most of the examined SMOTs showed the areas, covered with the endometrioid epithelium, with adjacent endometrial stroma, which indicated the development of carcinoma in the presence of endometrioid cyst. The revealed facts suggest that endometriosis plays an etiological role in developing SMOTs. When detected, most neoplasms are localized (limited to ovarian tissue, FIGO stage 1a) and characterized by a favorable prognosis as a whole.

© 2018 Bentham Science Publishers. The burden of cardiovascular and metabolic diseases is increasing with every year. Although the management of these conditions has improved greatly over the years, it is still far from perfect. With all of this in mind, there is a need for new methods of prophylaxis and treatment. Coenzyme Q10 (CoQ10) is an essential compound of the human body. There is growing evidence that CoQ10 is tightly linked to cardiometabolic disorders. Its supplementation can be useful in a variety of chronic and acute disorders. This review analyses the role of CoQ10 in hypertension, ischemic heart disease, myocardial infarction, heart failure, viral myocarditis, cardiomyopathies, cardiac toxicity, dyslipidemia, obesity, type 2 diabetes mellitus, metabolic syndrome, cardiac procedures and resuscitation.

© 2018 Stavropol State Medical University. All rights reserved. Male fertility is based on complex intracellular signaling during spermatogenesis. Effect of Interleukin-1 (IL-1) and its homologues on spermatogenesis is actively studied. Nevertheless, its role in idiopathic infertility has not been sufficiently studied, especially in the phase of hypospermatogenesis. Aim: Evaluation of the expression of IL-1α, IL-1β and IL-1ra in human seminiferous tubules in idiopathic infertility. A retrospective study involved men (n=54) who complained of childlessness in a marriage for 2 years with the diagnosis of idiopathic infertility, established after a physical, medico-genetic, biochemical (hormone) and cytological (spermogram) analysis. The biopsy specimens obtained from the operation, as well as the autopsy material of men aged 22-35 years (n=10), were studied using the immunohistochemical method (antibodies: IL-1α, IL-1β and IL-1ra). At hypo-spermatogenesis, the maturation block, and Sertoli-cell syndrome, Leydig cells are marked to IL-1α, IL-1β labeling with a decrease in IL-1ra. Sertoli cells and germ cells show weak responses to IL-1α, IL-1β and their absence on IL-1ra. Thus, the different levels of expression of IL-1α, IL-1β and IL-1ra indicate that these cytokines control spermatogenesis and are one of the triggers in the formation of male infertility form-phases.

© 2018 Media Sphera Publishing Group. All rights reserved. The All-Russian physical culture-sports set «Ready for Labour and Defense» (RLD) is a system that is aimed at health improvement and patriotic education of the nation. This system consists of strength, speed, endurance, agility, and flexibility tests. Statutory requirements for each discipline have been developed taking into account the age and gender characteristics of an organism. The main aim of the RLD set is to improve the population's health; therefore much attention is focussed on the issues of medical support. The medical support of the RLD set can be arbitrarily divided into several stages: to make preliminary medical examination and to gain access to RLD tests; to check whether medical access is available and complies with the health status of their participant at the time of the tests; to render medical care when the RLD standards are fulfilled. This paper proposes to consider the stepwise medical support of the RLD set in accordance with actual normative legal acts.

© 2018, V.A. Negovsky Research Institute of General Reanimatology. All rights reserved. Mechanical ventilation is associated with a number of complications that increase the cost of treatment and the hospital mortality rate. In 2004, the term «ventilator-induced diaphragm dysfunction» (VIDD) was proposed to explain one of the reasons for the failure of respiratory support. At present, this term is understood as a combination of atrophy and weakness of the contractile function of the diaphragm caused directly by a long-term mechanical lung ventilation. Oxidative stress, proteolysis, mitochondrial dysfunction, as well as passive overdistension of the diaphragm fibers contribute greatly to the pathogenesis of VIDD. Since 30—80% of patients in the ICU require mechanical respiratory support and even 6—8 hours of mechanical lung ventilation can contribute to the development of a significant weakness of the diaphragm, it can be concluded that the VIDD is an extremely urgent problem in most patients. Its typical clinical presentation is characterized by impaired breathing mechanics and unsuccessful attempts to switch the patient to the spontaneous breathing in the absence of other valid reasons for respiratory disorders. The sonography is the most informative and accessible diagnostic method, and preservation of spontaneous breathing activity and the use of the latest mechanical ventilation modes are considered a promising approach to prevention and correction of the disorders. The search for an optimal strategy for lung ventilation, development of diagnostic and physiotherapeutic methods, as well as the consolidation of the work of a multidisciplinary team of specialists (anesthesiologists and intensive care specialists, neurologists, pulmonologists, surgeons, etc.) can help in solving this serious problem. A review of 122 sources about the VIDD presented data on the background of the issue, the definition of the problem, etiology and pathogenesis, clinical manifestations, methods of diagnosis, the effect of drugs, prevention and therapy.

© 2018 SPIE. Laser radiation limiters can be made on the basis of working substances, which have strong nonlinear effects after reaching a certain critical value (threshold limiting). Thus, it becomes possible to obtain a high transmission for a safe beam and a sharply reduced transmission for a hazardous beam. To determine the nonlinear and linear optical properties of these materials there were carried out comprehensive spectroscopic studies, experiments by Z-scan methods with an open aperture and a fixed location of the limiter. Working substances was developed which is suspension of conjugates J-type phthalocyanine dimers Zn or Mg with single-walled carbon nanotubes (SWCNTs) in water. Created conjugates can be used not only for protecting eyes and light-sensitivity elements, but for forming three-dimensional tissueengineered structures. Using conjugates J-type phthalocyanine dimers Zn and Mg with SWCNTs will increase the optical absorption in the wavelength range of laser processing by reducing the thermal effect on other substances in the composition of this structure. The Nd:YAG laser was used as the laser radiation source for generating pulses of 16 ns duration at a wavelength of 532 nm with the linearly polarized laser beam in the horizontal plane and a shape of Gaussian type. The threshold of limiting, linear and nonlinear absorption coefficients were determined by output characteristic, that was obtained by fixed location of the limiter. Created working substances have values of the following order: linear absorption coefficient ∼ 3 cm-1 for layer of 0.2 cm thickness, low limiting threshold ∼ 1 MW·cm-2 and high value of the nonlinear absorption coefficient ∼ 550 cm GW-1. Knowing the nonlinear optical parameters, Z-scan data with an open aperture can be calculated for comparison with experimental data.

© 2018 Ima-Press Publishing House. All rights reserved. Certolizumab pegol (CZP) is the only pegylated biological agent (BA) that does not contain an Fc fragment, which minimizes its transplacental transfer. Takayasu arteritis mostly occurs in reproductive-aged women. Objective: to evaluate the efficacy and safety of CZP used to treat standard immunosuppressive therapy-resistant Takayasu arteritis. Subjects and methods. The retrospective study enrolled 6 female patients aged 18 to 35 years with Takayasu arteritis who received CZP. The median disease duration before BA usage was 66 months (24 to 204 months). The median duration of immunosuppressive therapy prior to CZP treatment was 92 months (14 to 132 months). All the female patients had taken glucocorticoids and methotrexate before and during CZP therapy. Only four patients had received two to five immunosuppressive drugs at different times prior to BA administration. Three patients had previously used other BAs. The disease activity was determined by the National Institute of Health (NIH) criteria. The Indian Takayasu Clinical Activity Score (ITAS2010) was used. The disease activity was recorded in all the patients prior to CZP therapy. Results and discussion. The median duration of CZP treatment was 17 months (6 to 24 months). The median erythrocyte sedimentation rate after CZP usage decreased from 22.5 to 10.5 mm/h; the median C-reactive protein level dropped from 7.8 to 0.39 mg/dl (p<0.05), the median daily dose of prednisolone was reduced from 20 to 8.75 mg (p<0.05). All the patients achieved complete remission an average of 4 months after starting CZP therapy. Three patients were still in remission after 12–24 months. One relapse of the disease was recorded following 24 months. ITAS2010 reduced from 1–4 to 0 in five patients and to 2 in one patient with recurrence. There was a good tolerance in five female patients. The adverse events were herpes labialis in two cases, community-acquired pneumonia in one case, and postoperative abscess in one case too. Conclusion. CZP in Takayasu arteritis was shown to be an effective drug for remission induction and maintenance. The presented results of the first experience in treating this disease with CZP are indicative of its promising further investigation as a steroid-sparing drug in patients with refractory vasculitis. One of the important advantages of CZP is its supposed high safety throughout pregnancy.

© 2018 Ima-Press Publishing House. All rights reserved. Objective: to determine the main factors associated with the development and manifestations of anxiety and depression spectrum disorders (ADSDs) in patients with Behcet’s disease (BD). Subjects and methods. This investigation was conducted within the framework of the interdisciplinary scientific program «Stress factors and mental disorders in rheumatic diseases». A total of 116 patients with BD were examined. Most of them were men (69.8%), whose mean age (M±σ) was 33.4±9.82 years; the median duration of BD was 120.0 [70.0; 192.0] months; 51.9% of the patients were natives of the North Caucasus. All the patients had a reliable diagnosis of BD according to the International Study Group for Behcet’s disease (ISGBD) criteria (1990). Disease activity was assessed using the Behcet’s Disease Current Activity Form (BDCAF); the subjective status of patients was evaluated using the visual analog scale (VAS) for general health assessment. ADSDs were diagnosed by a psychiatrist according to the ICD-10 during semi-structured interviews using the Hospital Anxiety and Depression Scale (HADS), the Hamilton Anxiety Rating Scale (HAM-A), and the Montgomery-Asberg Depression Rating Scale (MADRS). Clinical and psychological techniques were applied to assess cognitive functions (memory, attention, and logical thinking); stress levels were estimated by the 10-Item Perceived Stress Scale (PSS-10). Results and discussion. ADSDs were diagnosed in 91 (78.4%) patients with BD. The predominant RTDs were dys-thymia (39.6%) and recurrent depressive disorder (38.4%). Generalized anxiety disorder was found in only 7.69%, a single depressive episode was in 13.2%. Different degrees of cognitive impairment (CI) were observed in 91 (78.4%) patients. Multivariate analysis and linear regression were used to build a predictive model, from which it follows that ADSDs in patients with BD are primarily associated with sleep disorders (β=0.412), asthenia (β=0.149), CI (β=0.137), chronic stress (β=-0.010) and its severity (β=0.134), early childhood psychic trauma (ECPT) before the age 7 years (β=0.152), the development of ADSD before the onset of BD (β =0.160), older age of eye involvement in the pathological process (β=0.089), gastrointestinal tract (GIT) involvement within BD (β=0.096), high C-reactive protein (CRP) levels (β=0.177), and poor subjective status of patients (β=0.120) (area under the ROC-curve, 0.940). Conclusion. Chronic ADSDs are encountered with high frequency in patients with BD and frequently occur simultaneously with the latter or during its development. Their occurrence is favored to the greatest extent by ECPT and obvious chronic psychosocial stress preceding ADSDs. GIT involvement, late-onset ocular pathology, high CRP levels, and poor subjective status are common to patients with BD and ADSDs. Sleep disorders, asthenic syndrome, and CI are significant in the pattern of ADSDs.

© 2018 Ima-Press Publishing House. All rights reserved. Objective: to assess whether adalimumab (AD) can be gradually discontinued during continuous methotrexate (MTX) use in patients with early rheumatoid arthritis (ERA). Subjects and methods. Within the REMARCA (the Russian study of methotrexate and biological agents in early active arthritis) study, the investigators examined 20 patients (17 women and 3 men; median age, 51 [41.5; 56] years) with ERA (disease duration, 10 [5.5; 20] months; DAS28, 5.17 [4.37; 6.51]; 85% of the patients were seropositive for rheumatoid factor and 85% for anti-cyclic citrullinated peptide antibodies. Results and discussion. All the patients received subcutaneous MTX 25 mg/week. Twelve weeks after beginning therapy with MTX, due to its inefficiency, ADA was added according to the standard scheme. At week 24, the median DAS28 was 3.0 [1.65; 3.73]; 85% of the patients achieved remission or low disease activity. After 3 months of ADA therapy, high or moderate disease activity remained in 3 (15%) patients; median DAS28 was 4.4 [4.3; 6.1]; the drug was discontinued in them due to ineffective therapy. After 12-month follow-up, low DAS28 scores were observed in 5 (29.4%), DAS28 remission was in 12 (70.6%) of the 17 patients who continued ADA treatment; after 24 months, all the 17 patients were noted to have remission. After achieving sustained remission (≥ 6-month duration during ADA therapy), there was a carefully controlled reduction (titration) in the dose of ADA with its complete discontinuation, by maintaining remission at 36-month follow-up; the median DAS28 was 1.6 [1.4; 2.2]. During ADA treatment, one female patient developed pustular psoriasis and therefore the drug was discontinued at 24-month follow-up during the period of sustained remission. Other serious adverse events and tuberculosis cases were not recorded. Conclusion. Thus, the results of the study are indicative of the high clinical efficiency of the therapy. After ADA discontinuation, sustained remission can be maintained in patients with ERA and if they took biological agents early.

© 2018 Bentham Science Publishers. Background: This study discusses the crucial factors responsible for the progression of atherosclerotic cardiovascular disease (CVD). The interaction between the gut microbiota, heart and vessels in CVD pathogenesis is extremely complex and includes components such as direct bacterial translocation from the gut to vessels and metabolitemediated damage. To a greater extent, CVD seems to be entangled with a subtle immune system-to-microbiota interface. From among the most significant advances in recent years in this area, it is necessary to highlight the discovery of the pro-atherogenic effect of trimethylamine-N-oxide (TMAO) and changes in the activity of effector T-cells in the settings of dysbiosis. Currently, we are witnessing an explosive growth in interest in using the microbiota and interlinked cascades as a target for therapeutic interventions, including direct microbiome targeting, the attenuation of toxic metabolite-induced damage, the modulation of intestinal immunity, and downstream inhibition of systemic inflammatory pathways. Objective: In this brief review, modern strategies of microbiome-based therapies for the prevention and treatment of CVD are classified and discussed from the perspective of personalized medicine.

© 2018 Russian Transplant Society. All rights reserved. Aim. To evaluate the functioning of an implantable pediatric axial pump «DON-3» for bypassing the left ventricle of the heart in experiments on sheep. Materials and methods. Five sheeps at the age of 12–18 months performed paracorporeal installation of the children’s axial pump «DON-3» according to the scheme «left ventricle – aorta». Results. A technique was developed and 5 chronic experiments were conducted on sheep to assess the model of the children’s axial pump «DON-3». The duration of the experiments in this series averaged 9 ± 5 days. The main indicators of hemodynamics, acid-base balance were within the norm. Conducted morphological and histological studies of the kidneys, liver and lungs did not reveal the presence of zones of ischemia and thromboembolism. Conclusion. The results of this series of experiments showed satisfactory results, suggesting further research on the development of prototypes of a pediatric pump for clinical practice.

© 2018 Russian Transplant Society. All rights reserved. Tricuspid valve insufficiency is one of the most common variants of valve pathology of transplanted heart. The review is sanctified to the analysis of modern looks to on causes, potentially influencing on development of tricuspid valve insufficiency of transplanted heart, and also methods sent to declines risk his development.

© 2018 Media Sphera Publishing Group. All rights reserved. Objectives: This article reports 1-year clinical outcomes of patients with rheumatoid arthritis (RA) receiving abatacept (ABA) therapy. Materials and methods: Patients (n=91) with high RA activity (DAS28 = 5.1 ± 1.0) and an inadequate response on synthetic DMARDs (mainly methotrexate, 70.3%) and biologics (mainly TNF-α inhibitors, 93%) were included in the study. The majority of patients were middle- Aged (49 ± 13.5) womens, RF (72.5%) and ACPA (77%) positive, with moderate functional impairment - HAQ = 1.4 (0.9-2). ABA were administered IV, 10 mg/kg according to the standard scheme. The evaluation of the effectiveness of the therapy was carried out according to the EULAR / ACR 2011 criteria using SDAI, CDAI, HAQ and the intention to treat approach. Results: ABA led to a significant (p <0.05) decrease activity of RA. Clinical improvement according to EULAR criteria after 6 months of treatment was registered in 70.9%, after 12 months 63%. Almost a third of patients (28.7%) achieved a good response after 3 months of therapy, 39,2% - After 6 months and 39% - After 12 months. The retention rate of ABA therapy after 6 months was 77%, after 12 months - 60%. There were no significant differences between "bio-naive", 1 Bio and ≥2 Bio groups in achieving EULAR response. A good response was achieved in 38%, 38% and 43%, respectively, but the lowest number of non-responders was registered in ≥2 Bio - 38%, 36% and 43%. ABA significantly improved functional status of patients, after 12 months a marked and moderate improvement in the HAQ was achieved in 39% and 21% of patients, respectively. Adverse events (AE) were registered in 22 patients. The most frequent AE were upper respiratory tract infections - 11 (12%) patients. Conclusion: Abatacept was effective in the overall population, and in all subgroups of patients. It has shown significant improvement of clinical and functional status in patients who had an inadequate response to previous therapy. ABA has a good safety profile. AE were registered only in a small number of patients.

© 2018 ABC-press Publishing House. All rights reserved. The review is devoted to loop-mediated isothermal amplification (LAMP) - a novel molecular diagnostic method that has recently become increasingly popular. Unlike polymerase chain reaction, LAMP does not require thermal cycling; DNA or RNA amplification occurs at a constant temperature (about 65 °C) with 4 or 6 primers. This is a fast, highly-sensitive, and highly specific method, which does not require expensive equipment, where visual detection of the reaction products is performed by the unaided eye. LAMP is successfully used for the diagnosis of multiple viruses, bacteria, and other pathogens (including those in food). Moreover, it can be applied for the detection of single-nucleotide polymorphisms. Recently, a modified LAMP assay - one-step nucleic acid amplification (OSNA) - was validated for metastasis detection. OSNA was demonstrated to have almost the same sensitivity and specificity as standard diagnostic methods (sometimes even higher). Particular attention is paid to the mechanism of LAMP, primer design, and diagnostics of cancer using OSNA.

© 2018 Media Sphera Publishing Group. All rights reserved. Stomach's output part and small intestine, combining with damaging of the urinary tract is a rare systemic lupus eritematosus (SLE's) manifestation. The patient is 32 years old, suffering from SLE with damaged join, blood system, secondary antiphospholipid syndrome with pulmonary embolism in the history and formation of high postembolic pulmonary hypertension on therapy with hydroxychloroquine and low doses of corticosteroids, was hospitalized because of persistent nausea, vomiting, loss of more than 10 kg body weight 1.5 months. The research have shown the obstruction's formation of the stomach's output part, small bowel obstruction at several levels, as well as thickening of the bladder wall and the unilateral expansion of the ureter. Against the backdrop of strengthening of immunosuppressive therapy these lesions completely regressed.