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Aim. To assess the time course of changes in the level of glycated hemoglobin (HbA1c) for 20 years after the onset of type 1 diabetes mellitus (T1DM) and to compare its correlation with the development of microvascular complications, such as diabetic retinopathy (DR) and diabetic nephropathy (DN). Subjects and methods. A total of 187 children with new-onset T1DM were registered in Moscow in 1994. During the 20-year follow-up study, these patients underwent regular check-ups at the Endocrinology Research Center, Ministry of Health of the Russian Federation, which included assessment of physical data, HbA1c 2-4 times a year, biochemical blood and albuminuria tests (once per year), and ophthalmologic examination (twice a year). A total of 155 people fully completed the 20-years follow-up study. Results. During the 20-year follow-up period after the onset of T1DM, 86 of the 155 patients developed microvascular complications: DR and DN in 86 (55.5%) and 24 (15.5%) cases, respectively; while DR concurrent with DN were noted in 20 patients. By the time of their last visit, 69 (44.5%) patients had no evidence suggesting the presence of microvascular complications. The level of HbA1c at the onset of the disease in patients who later developed the complications was higher than in those without complications (10.2±0.6 and 8.5±0.2%, respectively (p = 0.003). The statistically significant differences in HbA1c levels between the groups persisted during subsequent 15 years of follow-up, averaging 9.2±1.5, 9.7±0.9, and 8.1±0.7% after 5, 10, and 15 years, respectively, in the complication group and 7.1±0.3, 8.1±0.4, and 7.2±0.2% in the non-complication group (p < 0.01). Over the last 5 years of the follow-up, the mean HbA1c level between the groups was not significantly different, which at the end of the 20-year follow-up period was 7.8±0.3 and 7.4±0.6%, respectively (p > 0.05). The mean duration of T1DM, in which DR developed, was 9.6±6.2, 11.0±2.0, and 13.6±4.6 years for the non-proliferative, pre-proliferative, and proliferative stages, respectively. That of T1DM, in which DN developed, was 11.8±0.6 years for microalbuminuria and 16.1±1.3 years for macroalbuminuria. Conclusion. The 20-year clinical follow-up of patients who had fallen ill with T1DM in childhood showed that diabetic microangiopathies developed with the long-term preservation of poor blood glucose control (BGC) starting at the onset of the disease. At the same time, the complications progressed to more severe stages, despite a clear trend toward better BGC. This may be suggestive of the negative metabolic memory phenomenon, which necessitates stable BGC, starting at the onset of the disease, for the prevention of microvascular complications.

Представлено краткое изложение клинических рекомендаций по диагностике и лечению остеопороза, разработанных членами Российской ассоциации эндокринологов при участии членов Российской ассоциации по остеопорозу (ревматологов, травматологов, терапевтов, гинекологов-эндокринологов). Рекомендации разработаны с позиций доказательной медицины, в соответствии с требованиями к составлению клинических рекомендаций Минздрава России, опубликованными в 2016 г. Значительное место в изложении отведено диагностике остеопороза у взрослых, дифференциальной диагностике с другими метаболическими заболеваниями скелета, а также принципам патогенетического лечения остеопороза. Клинические рекомендации полезны будут как врачам общей практики, так и специалистам, прежде всего эндокринологам, ревматологам, травматологам-ортопедам, гинекологам, нефрологам, гастроэнднрологам и неврологам, так как остеопороз является мультифакториальным и мультидисциплинарным заболеванием

This article discusses a lesser-known participant in the secret society and conspiracy of the Decembrists in St. Petersburg, merchant Alexander Petrovich Sapozhnikov (1788–1827). The relevance of this research lies in its engagement with a significant historiographical question regarding the maturation of opposition ideas to autocracy within the merchant class. The novelty of this work is defined by the unexplored relationships that connected A. P. Sapozhnikov with the Decembrists. The author has gathered scarce references from sources that illuminate the circumstances surrounding the entry of a merchant family member into the Decembrist union, his involvement in the conspiracy of 1825, and the “demarche” of his relative, Ya. I. Rostovtsev, related to the intentions of moderately inclined Decembrists to achieve limitations on autocracy through non-violent means. The evidence from the sources is compared, and the degree of their authority and reliability is assessed. An interpretation of the documentary data is conducted based on a critical analysis of their comprehensive content. The reasons for A. P. Sapozhnikov’s avoidance of punishment are reconstructed. Unique information is presented regarding the “freethinking” of the Sapozhnikov family, which influenced this representative’s alignment with the Decembrist movement. The findings suggest the emergence of like-minded individuals among the “elite layer” of merchants, while simultaneously revealing the efforts of Decembrist union members to extend their influence into the merchant class.

Aim. To study the markers of renal graft dysfunction in patients with type 1 diabetes mellitus (T1DM) after kidney transplantation (KT) and simultaneous pancreas-kidney transplantation (SPKT). Subjects and methods. The investigation enrolled 20 patients after successful SPKT and 41 patients after KT (of them 21 received continuous subcutaneous insulin infusion with an insulin doser; 20 had multiple insulin injections). The periods after KT and SPKT at patient inclusion were 8 (7; 8) and 11 (8; 18) months, respectively. A control group comprised 15 patients with T1DM without diabetic nephropathy. The patients were matched for gender, age, and T1DM duration. At a 9-month follow-up, the main biomarkers of kidney graft dysfunction were identified using the standard kits: Cystatin C (Cys C; serum; urine), NGAL, KIM-1, Podocin, Nephrin, IL-18, MMP-9 (urine), TGF-β1, VEGF-A, and Osteopontin (OPN; serum). Fasting blood was taken; a morning urinary portion was examined. Results. The posttransplantation glomerular filtration rate (GFR) in the patients corresponded to Stage C2; albuminuria did to Category A1 chronic kidney disease. Despite successful SPKT in the group of patients with T1DM, as in that of patients after isolated KT, there was a statistically significant increase in the level of kidney dysfunction markers (Cys C, NGAL, Podocin, and OPN) versus the control group regardless of the compensation for glucose metabolism. compensation. It was found that the level of Cys C was high and correlated negatively with GFR (r=–0.36; p

Aim. To implement in 2009—2012 the RESULT observational program on the use of insulin glargine (Lantus) in combination with insulin glulisine (Apidra) as a basal-bolus regimen in patients with type 1 diabetes mellitus (DM) to evaluate the efficiency and safety of therapy with human insulin analogues. Subjects and methods. The program covered 100 patients aged 19 to 25 years from 7 regions of the Russian Federation, who had had DM onset at the age of 9—13 years, were using human recombinant insulins as continuous insulin therapy, and had glycated hemoglobin (HbA1c) levels of 7 to 9%. The main inclusion criterion was switching to insulin therapy with the human insulin analogues Lantus and Apidra. Results. A total 41 men and 59 women were followed up. Their mean baseline HbA1c level was 8.3±0.7%. After 24 months of therapy, HbA1c was significantly decreased to 7.7±0.7%; its change compared with that at Visit 1 was –0.6±0.6% (p

Aim. To investigate the nonglycemic effects of incretins in patients with type 1 diabetes mellitus (DM1) of long duration (for more than 20 years) and chronic kidney disease. Subjects and methods. Seventy-five patients with varying degrees of diabetic nephropathy (DN) and without this condition, including patients receiving renal replacement therapy with programmed hemodialysis and those who had undergone kidney transplantation were examined. The levels of phosphorus-calcium metabolic indicators (calcium, phosphorus, parathyroid hormone, vitamin D, and fibroblast growth factor 23 (FGF-23)), the cardiac damage marker atrial natriuretic peptide, the proinflammatory markers monocyte chemoattractant protein 1 (MCP-1) and C-reactive protein (CRP) and the fibrotic marker transforming growth factor-β, as well as those of glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP) were estimated in addition to conventional examination methods. All the patients underwent cardiac multislice spiral computed tomography, by calculating the Agatston index (calcium index (CI)) reflecting the degree of coronary artery calcification. Results. The investigation revealed no relationship of GLP-1 and GIP levels to the presence and degree of DN in the patients of the study groups. GLP-1 was noted to be inversely related to patient age, indicating the diminished secretion of this peptide in older people. There was evidence that GLP-1 positively affected blood lipid composition (total cholesterol: r=–0,320; p

In the study were enrolled 137 patients with medullary thyroid cancer (MTC). Low 35%-sensitivity of FNAC and high accuracy of basal calcitonin in MTC diagnostics were found. Mutation analysis of the RET pro- tooncogene in familial and sporadic MTC, RAS -gene in sporadic MTC were done. The correlation between type of the mutation and disease aggressiveness was found.

This article addresses the misidentification of Colonel Pavel Rennenkampf, a member of the Southern Decembrist conspiracy and a colonel in the General Staff (1790-1857), by historians. Through the examination of investigative materials, police reports, official correspondence, and memoirs, the author aims to establish the documentary evidence supporting Pavel Rennenkampf’s involvement in the Decembrist movement. It is concluded that this officer played a significant role in S.I. Muravyov-Apostol’s plans for organizing the uprising of the Chernigov Regiment, dedicated to the secrecy of the military conspiracy and its political goals. The research novelty lies in shedding light on an understudied figure in Decembrist history, previously overlooked by historiography. The relevance of this study lies in its contribution to understanding key events in the Decembrist movement — the Southern conspiracy and uprising. The article discusses why the incriminating evidence indicating P.Ya. Rennenkampf's involvement in clandestine societies was dis-regarded during historical proceedings and remained largely unnoticed by historians. The author provides an explanation for the long-standing misattribution of K.P. Rennenkampf instead of P.Ya. Rennenkampf in historical accounts.

Purpose. Endogenous Cushing’s syndrome (CS), usually affecting young and otherwise healthy patients, is a good model to validate the effects of supraphysiological levels of glucocorticoids in humans. This study evaluates circulating levels of extracellular antagonists of Wnt/ß-catenin signaling pathway (sclerostin, Dickkopf1 (Dkkl), secretedfrizzled-related protein 1 (SFRP1)) along with osteoprotegerin (OPG) and soluble receptor activator of nuclear factor kappa-beta ligand (RANKL) in patients with CS as compared to healthy individuals. Materials and methods. Forty patients with clinically and biochemically evident CS and 40 sex, age and body-mass index matched healthy individuals provided fasting serum samples (8:00-10:00AM) for measurement of sclerostin, SFRP1 and Dkkl, RANKL., OPG along with bone turnover markers. Serum samples on RANKL., OPG., Dkkl, SFRP1, sclerostin were frozen and then concurrently measured by an enzyme immunoassay (ELISA) using commercially available reagents. Serum samples on osteocalcin (OC), carboxyterminal cross-linked telopeptide of type I collagen (CTx), cortisol in serum and saliva were assayed by electrochemiluminescence (ECLIA) Cobas e601 Roche. Urinary free cortisol (24hUFC) was measured by an immunochemiluminescence assay (extraction with diethyl ether) on a Vitros ECi. All participants were questioned regarding any recent low traumatic fractures. Patients with CS underwent standard spinal radiographs in anterior-posterior and lateral positions of the vertebrae Th4-L4 (Axiom Icons R200 "Siemens"). Results. Patents with CS (30 (26-40) years old with 24hUFC 2575 (1184-4228) nmol/l (Me (Q25-Q75)) had suppressed OC and normal CTx levels as compared to healthy subjects. A significant correlation, which we observed between OC and CTx (po=0.724 (p

Aim. To compare effects of atorvastatin treatment and carbohydrate metabolism compensation on lipid spectrum and a C-reactive protein (CRP) level in patients with type 2 diabetes mellitus (DM). Material and methods. The lipid spectrum was studied in a random sample of 165 patients (66 males, 99 females) with type 2 DM (age median 57 years, duration of the disease 7 years). Out of this sample 26 patients with LDLP cholesterol > 3 mmol/l were randomized into 2 groups. The study group received 20 mg/day atorvastatin for 3 months, the control group received no inhibitors of GMG-Coa-reductase. The patients' blood was tested for glycosylated hemoglobin, aminotransferase, creatinphosphokinase, total, HDLP, LDLP cholesterol. Results. Changes in the lipid spectrum were detected in 98.2% patients, 42.4% of them had combined dyslipidemia: elevated total cholesterol (TC), LDLP cholesterol, triglycerides (TG) and low HDLP cholesterol. After 3 months of therapy both groups demonstrated the same significant lowering of HbA1c. The control group had also elevated level of HDLP cholesterol, unchanged levels of TC, LDLP cholesterol, TG. 3-month therapy with atorvastatin lowered TC from 6.41 to 4.76 mmol/l, LDLP cholesterol from 4.19 to 1.87 mmol/l, TG from 2.69 to 1.62 mmol/l, apo B from 1.64 to 1.13 mg/dl, raised HDLP from 0.99 to 1.21 mmol/l (p < 0.05). CRP fell from 5.65 to 2.33 mg/dl (p = 0.026) irrespective of carbohydrate metabolism compensation (CRP in the control group did not change). Conclusion. More than 98% type 2 diabetics have atherognic impairment of the lipid spectrum. Atorvastatin produces an antiatherogenic effect due to both improvement of the lipid metabolism and CRP level reduction irrespective of the degree of compensation of carbohydrate metabolism in type 2 DM.

Introduction. Surgical intervention remains the main method for treatment of the oral mucosa cancer. The generally accepted standard of the resection boundary that provides optimal local control is 5 mm. Adequate boundaries of indentation and choice of the reconstruction method are important issues facing specialists in head and neck tumors. Aim. To evaluate parameters of the resection edge in the surgical treatment of malignant neoplasms of the oral mucosa depending on the method of eliminating of the post-resection defect and its effect on the frequency of local relapse. Materials and methods. A retrospective analysis included 168 primary patients (50 % men and 50 % women) who received surgical treatment in the head and neck tumor department of the Republican Clinical Oncology Dispensary of the ministry of Health of the Republic of Bashkortostan (ufa) from 2019 to 2023. The median age of patients was 63 years (interquartile range (IQR) 55–69 years). most often, the primary tumor was located in the tongue – in 59.5 % (100/168) of cases. According to the method of post-resection defect removal, the patients were divided into 3 groups. In group 1, reconstruction was performed with local tissues (n = 71), in group 2 – with pedicle flaps (n = 41), and in group 3 – with revascularized flaps (n = 56). The median follow-up period was 18 months (IQR 8–28 months). Results. Resection boundaries in group 1 were 7.0 mm (IQR 5.0–12.5 mm), in group 2 – 6.5 mm (IQR 5–13 mm), and in group 3 – 12.5 mm (IQR 7.5–15.0 mm). The overall frequency of near/positive resection boundaries was 14.8 % (25/168). In group 1, it was 15.5 % (11/71), in group 2 – 19.5 % (8/41), in group 3 – 10.7 % (6/56). According to the analysis, relapse of the disease after radical treatment was noted in 32 % (55/168) of patients, of which 14.8 % (25/168) had a local relapse, 12.5 % (21/168) had a regional relapse, and 5.4 % (9/168) developed distant metastases. The frequency of local relapse in group 1 was 18.3 % (13/71), in group 2 – 23.8 % (10/41), in group 3 – 5.5 % (3/56). According to the analysis data, statistically significant differences in the boundary of indentation in the groups were revealed depending on the reconstruction method (p = 0.005). Conclusion. Based on the results of the present retrospective analysis, the choice of reconstruction method affects the resection boundary in real clinical practice. Limitations in the surgical indentation that surgeon faces when choosing a method for eliminating a post-resection defect are demonstrated.

The discussion aims to identify the interpretive mechanisms that provide an interface be­tween text and context (between language and the world, language and culture, language and society). It is a multi-level system of interfaces connected by inversion and recursion relations and operations. We identify this system as a pragmasemantics. It also acts as an interface platform for correlation/transformation of intra-system semantic units and extralinguistic objects within a set of possible worlds. At the same time, this platform is endowed with the autopoietic potential to generate new operating interfaces systems, as well as textualized structures of operations and interpretations (instructions, memory, reframing). The genera­tion of meaning is the result of the interaction of the system platform with the platform-as-context, due to the possibility that one generates and determines the operational potential of the other, acting a recursive loop or Möbius strip. The connection between subjectivity and meaningful semiosis is crucially important due to the key role of textualization and langua­ging. The signified are reproduced by signifiers and thus generate those processes that are structured by interactions and other practices. In complex systems (biological and beyond), the possibility of self-replication arises through recursive self-interpretation. Thus, subjectivi­ty acts as a kind of universal interface that determines the change of contexts, their interac­tion, the generation of possible new ones, ensuring the pro-creativity and pre-adaptability of the system (its stability and development.

We report discovery and spectroscopic follow-up of 21 astrometric binaries containing solar-type stars and dark companions with masses near 1.4 $M_{\odot}$. The simplest interpretation is that the companions are dormant neutron stars (NSs), though ultramassive white dwarfs (WDs) and tight WD+WD binaries cannot be fully excluded. We selected targets from Gaia DR3 astrometric binary solutions in which the luminous star is on the main sequence and the dynamically-implied mass of the unseen companion is (a) more than $1.25\,M_{\odot}$ and (b) too high to be any non-degenerate star or close binary. We obtained multi-epoch radial velocities (RVs) over a period of 670 days, spanning a majority of the orbits' dynamic range in RV. The RVs broadly validate the astrometric solutions and significantly tighten constraints on companion masses. Several systems have companion masses that are unambiguously above the Chandrasekhar limit, while the rest have masses between 1.25 and 1.4 $M_{\odot}$. The orbits are significantly more eccentric at fixed period than those of typical WD + MS binaries, perhaps due to natal kicks. Metal-poor stars are overrepresented in the sample: 3 out of 21 objects (14%) have [Fe/H]$\sim-1.5$ and are on halo orbits, compared to $\sim 0.5\%$ of the parent Gaia binary sample. The metal-poor stars are all strongly enhanced in lithium. The formation history of these objects is puzzling: it is unclear both how the binaries escaped a merger or dramatic orbital shrinkage when the NS progenitors were red supergiants, and how they remained bound when the NSs formed. Gaia has now discovered 3 black holes (BHs) in astrometric binaries with masses above 9 $M_{\odot}$, and 21 NSs with masses near $1.4\,M_{\odot}$. The lack of intermediate-mass objects in this sample is striking, supporting the existence of a BH/NS mass bimodality over 4 orders of magnitude in orbital period.

We report discovery and characterization of a main-sequence G star orbiting a dark object with mass $1.90\pm 0.04\,M_{\odot}$. The system was discovered via Gaia astrometry and has an orbital period of 731 days. We obtained multi-epoch RV follow-up over a period of 639 days, allowing us to refine the Gaia orbital solution and precisely constrain the masses of both components. The luminous star is a $\gtrsim 12$\,Gyr-old, low-metallicity halo star near the main-sequence turnoff ($T_{\rm eff} \approx 6000$\,K; $\log\left(g/\left[{\rm cm\,s^{-2}}\right]\right)\approx 4.0$; $\rm [Fe/H]\approx-1.25$; $M\approx0.79\,M_{\odot}$) with a highly enhanced lithium abundance. The RV mass function sets a minimum companion mass for an edge-on orbit of $M_2 > 1.67\,M_{\odot}$, well above the Chandrasekhar limit. The Gaia inclination constraint, $i=68.7\pm 1.4$\,deg, then implies a companion mass of $M_2= 1.90\pm 0.04\,M_{\odot}$. The companion is most likely a massive neutron star: the only viable alternative is two massive white dwarfs in a close binary, but this scenario is disfavored on evolutionary grounds. The system's low eccentricity ($e=0.122\pm 0.002$) disfavors dynamical formation channels and implies that the neutron star likely formed with little mass loss ($\lesssim 1\,M_{\odot}$) and with a weak natal kick ($v_{\rm kick}\lesssim 20\,\rm km\,s^{-1}$). Stronger kicks with more mass loss are not fully ruled out but would imply that a larger population of similar systems with higher eccentricities should exist. The current orbit is too small to have accommodated the neutron star progenitor as a red supergiant or super-AGB star. The simplest formation scenario -- isolated binary evolution -- requires the system to have survived unstable mass transfer and common envelope evolution with a donor-to-accretor mass ratio $>10$. The system, which we call Gaia NS1, is likely a progenitor of symbiotic X-ray binaries and long-period millisecond pulsars. Its discovery challenges binary evolution models and bodes well for Gaia's census of compact objects in wide binaries.

The consistently low activity level of the old solar analog 51 Peg not only facilitated the discovery of the first hot Jupiter, but also led to the suggestion that the star could be experiencing a magnetic grand minimum. However, the 50 yr time series showing minimal chromospheric variability could also be associated with the onset of weakened magnetic braking (WMB), where sufficiently slow rotation disrupts cycling activity and the production of large-scale magnetic fields by the stellar dynamo, thereby shrinking the Alfvén radius and inhibiting the efficient loss of angular momentum to magnetized stellar winds. In this Letter, we evaluate the magnetic evolutionary state of 51 Peg by estimating its wind braking torque. We use new spectropolarimetric measurements from the Large Binocular Telescope to reconstruct the large-scale magnetic morphology, we reanalyze archival X-ray measurements to estimate the mass-loss rate, and we detect solar-like oscillations in photometry from the Transiting Exoplanet Survey Satellite, yielding precise stellar properties from asteroseismology. Our estimate of the wind braking torque for 51 Peg clearly places it in the WMB regime, driven by changes in the mass-loss rate and the magnetic field strength and morphology that substantially exceed theoretical expectations. Although our revised stellar properties have minimal consequences for the characterization of the exoplanet, they have interesting implications for the current space weather environment of the system.

Introduction. Basal cell carcinoma is the most common type of non-melanocytic malignant tumors of the skin. The main treatment methods for this pathology are local methods such as surgery and radiation. In rare cases, basal cell carcinoma can become locally advanced and / or metastatic.Aim. To demonstrate the possibility of reconstructive surgery for large defects after removal of locally advanced tumors of the face and describe a rare case of basal cell carcinoma metastasis into the regional lymph nodes.Clinical case. The article presents a clinical case of treatment of basal cell skin cancer with metastases into the regional lymph nodes. According to the patient, tumor on the skin of the left cheekbone area first appeared in 2007. The patient did not seek medical help. In 2017, the tumor was resected at the local medical facility. In 2018, the patient noted repeat tumor growth. In November of 2021, when the patient first consulted at the Republican Clinical Oncological Dispensary of the ministry of Health of the Bashkortostan Republic, the tumor was 7 × 5 cm. Invasion depth was up to 1.5 cm, infiltration into the temporal and mastication muscles and destruction of the zygomatic bone were observed. On 18.11.2021 at Republican Clinical Oncological Dispensary of the ministry of Health of the Bashkortostan Republic, wide resection of the skin tumor with resection of the zygomatic arch, parotidectomy on the left with defect removal using anterolateral thigh flap was performed. per histological examination, basal cell carcinoma with lymphovascular and perineural invasion and advancement into the masticator muscle and zygomatic bone was diagnosed, as well as carcinoma metastases in 2 lymph nodes with advancement beyond the capsule.Conclusion. Implementation of revascularization flaps significantly widens choices for surgical treatment of this patient group in a regional oncological dispensary and gives satisfactory esthetic results due to removal of large defects after surgical intervention.

Methods: Were examined 145 patients with Hodgkin’s lymphoma (HL) II-IIIAB who received AHF within 1985-1997. A comparison was carried out with the comparable group of 110 patients given CF. The AHF schedule was carried out by admission of the single dose 1,35 Gy twice a day with interval 3,54 hs to basic registration points (bifurcation of trachea and paraaortal lymphatic nodes). The total doses in clinically involved nodes were approximately 40 Gy; zones of subclinical involvement — 36 Gy.Results: Objective response was obtained 87,4% in the AHF group and 90,0% in the CF group. Median follow-up was 144 months: AHF - 144 months, CF — 150 months. Quantity of recurrences was significantly higher in patients with CF than in those with AHF — 28,3% and 16,5% (p=0,02), respectively. 10-years overall survival was 82,8% in AHF group and 72,1% in the CF group. 10-year recurrence-free survival was 81,5% in the AHF group and 69,8% in the CF group (p=0,04). Analysis of clinical date showed essential reduction of radiation pneumonitis rate at AHF in comparison with CF: 13,1% vs. 25,4% (p=0,01), postradiation pericarditis: 2,1% vs. 7,3% (p=0,04), leucopenia grade IV: 4,1% vs. 12,7%.Conclusions: Clinical analysis revealed the benefits of single dose decrease from 2 Gy to 1,35 Gy at the twice a day irradiation scheme. The AHF is an effective schedule of RT and promotes to the recurrence frequency reduction, increases recurrence-free survival, decreases of the cardiopulmonary complication risk and leucopenia rate.

The article discusses the treatment of osteoarthritis (OA). In recent decades, ideas about the pathogenesis of OA have undergone significant changes. If at the dawn of the study OA was presented as a degenerative process associated with age, now that some immunological and genetic aspects of the disease have become known, the idea of the pathogenesis of OA has changed. Currently, there are clinical guidelines developed by professional communities that define approaches to the diagnosis and treatment of patients with OA. In Russia, the Association of Rheumatologists and Orthopedic Traumatologists in 2021 developed clinical guidelines for the management of patients with gonarthrosis and coxarthrosis, but currently no clear consensus has been developed in any of the treatment recommendations regarding the use of nutraceuticals and dietary supplements. While according to published studies of plant and botanical nutraceuticals developed from natural products, promising data on efficacy compared to placebo drugs and their potential for the treatment of patients with OA have been demonstrated. According to a study conducted by N.E. Lane et al., patients with OA regularly use supplements, as well as over-the-counter products in combination with prescription drugs, and the likelihood of using prescription products increases with increasing duration and severity of OA. And currently there is not enough knowledge and information about the possibilities of additional use of nutraceuticals in the treatment of patients. The article discusses the composition of the biologically active additive, which has anti-inflammatory, anti-catabolic and antiproliferative effects and can be considered as an addition to NSAIDs, chondroitin sulfate, glycosamine (sulfate or hydrochloride) and their combinations in OA. Type II collagen peptide, curcumin (curcuminoids 95%), black pepper extract (piperine) and Boswellia pilchata extract in clinical studies have demonstrated efficacy and safety in the treatment of patients with OA. A number of studies have also found a number of pleootropic effects. Effects such as anti-inflammatory, neuroprotective, immunomodulatory, cardioprotective and antitumor effects will be important in patients with comorbidity.

Introduction. The scattering patterns of non-absorbing coded checkerboard-like meta-coatings (MCs) applied for reducing the radar cross section (RCS) of metal surfaces inevitably contain side diffraction lobes. Therefore, the development of MCs with a low level of diffraction lobes is relevant. For this purpose, it is proposed to use checkerboard-like MCs in the form of a set of several basic flat blocks with the same dimensions. The paper discusses two such basic MC blocks with different coding matrices. The cells of the metasurface contain two coupled elliptical ring resonators and are distinguished by a 2-bit coding of the tilt angle of the anisotropy axis. Coding matrices of the MC blocks are built according to the block principle.Aim. To investigate experimentally and numerically backscatter patterns (BSP) for consonant (co-) and orthogonal (cross-) polarizations of the two developed flat blocks of the 2-bit digital nonabsorbing anisotropic MCs for different planes and polarizations of irradiation.Materials and methods. Full-wave simulation of the MC blocks was carried out using the HFSS software by the finite element method. BSP measurements of the fabricated MC layouts were performed in an anechoic chamber of the Center for Collective Usage “Applied Electrodynamics and Antenna Measurements” of the Southern Federal University using an automated information and computing complex.Results. The RCS reduction for the two blocks under normal irradiation is approximately the same and not less than 12 dB over the 9.8…21 GHz band. A good matching between the simulation and measurement results of backscattering patterns of the blocks in the region of the central lobes for various planes and polarizations of the irradiation is noted. In the principal planes, the blocks cancel the central lobes of the BSP by 10…25 dB; in the sector of angles of around ±40°, the backward RCS of the blocks is lower than that of the reference. In the diagonal planes, there is a cancellation of the RCS by 13…15 dB and an expansion of the central lobe of the BSP for copolarizations, as well as a bifurcation of this lobe for crosspolarizations in the sector of angles ±9°; outside of this sector the RCSs of the blocks are commensurate with the RCS of the reference.Conclusion. The developed blocks of the 2-bit digital nonabsorbing anisotropic MCs can be used for broadband cancellation of the RCS of metal surfaces.

An online expert meeting held on November 17, 2021 reviewed the results of the randomized, double-blind, multinational, parallel-group EMPULSE trial, evaluating the clinical benefit and safety of the sodium-glucose co-transporter-2 inhibitor (SGLT2i) empagliflozin compared with placebo in patients hospitalized with acute decompensated heart failure (ADHF). Patients were included in the study regardless of ejection fraction (EF) and the presence of diabetes and randomized during hospitalization after stabilization. In addition, the EMPULSE trial used a composite result analyzed using a stratified benefit ratio — Win Ratio analysis. There is evidence of clinical benefit of empagliflozin in hospitalized patients with preserved and reduced LVEF, as well as in patients with newly diagnosed ADHF or with acute decompensation of chronic heart failure (CHF) compared with placebo, regardless of type 2 diabetes presence. The importance of the favorable results of the EMPULSE trial and its significance for clinical practice, which implies the early administration of empagliflozin for inpatients, is noted. A number of proposals have been adopted to accelerate the introduction of empagliflozin into clinical practice for patients with ADHF.

This article outlines major trends in the development of social semiotics during the last four decades of its existence. The starting point was the interface between functional analysis of the semiotic system of language and the structural interpretation of language as a social system. Their convergence provided the basis for further developing an interdisciplinary domain of social semiotics. Michael Halliday’s book “Language as social semiotic: The social interpretation of language and meaning” (1978) gave an initial impetus to exploring the interface of semiotic and social. Ten years later his approach was reinterpreted by Bob Hodge and Gunther Kress in “Social Semiotics” (1988). They suggested that both the social and semiotic nature of language had a broader significance and extends to the entire domain of human activity and existence. Thus, social semiotic (in singular) of language was enhanced into all-embracing social semiotics (in plural). This article further examines linguistic as socio-semiotic, semiotic as social, semiotic as multimodal, socio-semiotic as functional, interpretative as socio-semiotic. The article outlines two frontiers of social semiotics, that of its subject matter and that of its methodological dimension. Finally, the article focuses on current challenges faced by social semiotics, particularly those relevant to sociology.

Objective: to analyze the clinical and organizational feasibility of using different intervention thresholds for the Russian population.Subjects and methods. The probability of fractures using the Russian FRAX model was calculated on a sample of 3,866 postmenopausal female residents from 6 cities of the Russian Federation. Different intervention thresholds, including fixed (20% for major fractures and 3% for hip fractures), age-dependent (European and Russian) ones, as well as alternative models, were analyzed. The proportion of women to be treated was estimated using different intervention thresholds.Results and discussion. The analysis of the effectiveness of the thresholds showed that the European threshold was the least appropriate one for the formed sample, since more than half (53.6%) of the women to be treated using the threshold, while the vast majority (90%) of the patients were in the younger age groups (50—54 years). There were very similar results of the effectiveness analysis of the fixed threshold (according to the USA National Osteoporosis Foundation — NOF) recommendations and that of the age-dependent threshold for Russia (in the context of the national clinical recommendations). Using the NOF approach in our sample could identify 47.8% of the postmenopausal women to be treated for osteoporosis. Their proportion rose from 29.6% of the patients aged 50—54 years to 80.6% of those aged 85 years and older. The alternative analyses of age-dependent thresholds showed great effectiveness when the fracture was considered not as a risk factor for future fractures, but as a clinical disease manifestation that was sufficient to recommend that the patient should be treated without FRAX counting. However, with their use, the proportion of older people to be treated remains not high enough. In this connection, there remains a need to search for the more adequate application of the existing intervention threshold or to develop a new, for example, hybrid variant of the age-dependent threshold.

Pulmonary arterial hypertension (PAH) is a rare chronic life-threatening disease. The treatment standards for PAH patients emphasize the need for early intervention and achievement of all treatment goals with the use of monotherapy or combinations. To date, strong evidence has been obtained that combination therapy with PAH-specific medications can significantly inhibit the development of the disease. Therefore, in modern guidelines, combination therapy is considered as a treatment standard for a significant proportion of patients with PAH. This publication presents a modern view of the selexipag practical using in early combination therapy in patients with PAH.

The results of complex studies of the quantitative relationship between the stage-by-stage mass transfer of O2 and the efficiency of cardiorespiratory system functioning in relation to its consumption in adolescents’ body under conditions of relative rest are presented. The results obtained show that in adolescents, the modes of mass transfer of O2 in the body and the nature of the respiratory and circulatory systems functioning in relation to its consumption have a number of age-related differences compared with adult men. So, in adolescents, the external respiration system at rest functions less economically than in adults. Each liter of O2 consumed by adolescents is extracted from almost 3 liters more than in adults the amount of air ventilated per minute through the lungs. The volumetric indicators of blood circulation are also higher in adolescents, which may indicate the influence of neuro-humoral rearrangements in the body during the pubertal period. The coefficient of oxygen utilization by tissues from arterial blood in adolescents turned out to be significantly higher, which may characterize a higher tension of tissue metabolic processes.

In the present paper the application of the kinetic methods to the blood flow problems in elastic vessels is studied. The Lattice Boltzmann (LB) kinetic equation is applied. This model describes the discretized in space and time dynamics of particles traveling in a one-dimensional Cartesian lattice. At the limit of the small times between collisions LB models describe hydrodynamic equations which are equivalent to the Navier - Stokes for compressible if the considered flow is slow (small Mach number). If one formally changes in the resulting hydrodynamic equations the variables corresponding to density and sound wave velocity by luminal area and pulse wave velocity then a well-known 1D equations for the blood flow motion in elastic vessels are obtained for a particular case of constant pulse wave speed. In reality the pulse wave velocity is a function of luminal area. Here an interesting analogy is observed: the equation of state (which defines sound wave velocity) becomes pressure-area relation. Thus, a generalization of the equation of state is needed. This procedure popular in the modeling of non-ideal gas and is performed using an introduction of a virtual force. This allows to model arbitrary pressure-area dependence in the resulting hemodynamic equations. Two test case problems are considered. In the first problem a propagation of a sole nonlinear pulse wave is studied in the case of the Laplace pressure-area response. In the second problem the pulse wave dynamics is considered for a vessel bifurcation. The results show good precision in comparison with the data from literature.

The study objective is to evaluate the possibility of determining the signaling lymph node (SLN) in oral cancer (T1–2N0M0) with lymphoscintigraphic method.Materials and methods. In 2016–2018, SLNs were determined for 23 patients with oral cancer (cT1–2N0M0): for 15 patients with cancer of the tongue, for 8 patients with cancer of the floor of the mouth cavity. SLNs were determined by radiolymphoscintigraphic method by peritumoral administration of Tehnefit radiopharmaceutical in a dose of 40 to 80 MBq, depending on the timing of the signal lymph node biopsy. Visualization of the signaling lymph node was carried out by planar scintigraphy and single-photon emission computed tomography combined with x-ray computed tomography. Intraoperative SLN was detected using intraoperative radiometry using a gamma probe.Results. In cancer of the floor of the mouth, SLNs were identified only in 2 (25 %) of 8 cases. In cancer of the language, SLN were identified in 14 (93.3 %) of 15 cases. In total, SLNs were diagnosed with cancer in 17 patients. In 4 (26.7 %) of 15 patients, cancer metastases in SLNs were identified. False negative results were obtained in 6.7 % of cases.Conclusion. A biopsy of the SLN by the lymphoscintigraphic method has a high diagnostic value for staging the early stages of cancer of the tongue.

Introduction. Arterial hypertension is one of the most serious problems of the contemporary health care. Within the qualimetric approach and quantification of “lifestyle” capacity. However, research papers dealing with the relationship impact medical care cardiac profile and complete realization of the potential of the lifestyles of patients, it is not enough. The purpose of the research is to explore the potential lifestyle hypertensive patients and its role in ensuring the effectiveness of the treatment.Materials and methods. The study was conducted on the basis of the medical organizations of the Kostroma region. Research methods: expert, sociological, analytical, statistical. Analysed data on 400 patients a cardiac profile: lifestyle parameters monitoring data of patients using the original automated management factors impact medical care Cardiac profile, data expert evaluation of physician lifestyles of the patient and the patient questionnaire survey, consisting of 8 questions.Results and discussion. Found that in patients with arterial hypertension has reduced the capacity of lifestyle for all its components, including the low level of medical activity, low level of medical awareness, inadequate recreational activity disregard for the principles of a balanced diet, the prevalence of bad habits. There are significant differences in the potential lifestyle of patients with low and high levels of treatment success, proving the importance of lifestyle modification patients, his healing in the practice of primary care physicians health.Conclusions and proposals. It is recommended that the monitoring capacity of the lifestyles of patients with arterial hypertension in the context of district clinics.

At the online meeting held on September 3, 2020, the results of the international multicenter trial EMPEROR-REDUCED were considered. Number of proposals and recommendations for the further study of cardiovascular and renal effects of empagliflozin and its practical use in heart failure patients were agreed.

The paper is addressed to the actual problem of verification of large-scale data models applied in various industrial areas and specified using popular general-purpose object-oriented languages, such as EXPRESS, UML/OCL. Main benefits of information modeling languages (high expressiveness, declarative nature, advanced set of syntactic units) negatively affect the process of automatic verification of the specifications. The known approaches are based on reduction of the original complex problem to some well-known mathematical statement and its solution by existing methods. The performed analytical survey of the existing methods for model verification demonstrates that they cannot be used for solving the problem because of their high computational complexity. A combined method for verification of large-scale data models is proposed in the paper. The method is based on sequential reduction to the several mathematical problem statements: linear programming, constraint satisfaction problem (CSP), Boolean satisfiability (SAT). Usage of the combined method allows to avoid efficiency issues peculiar to the known approaches. At the first step the polynomial complexity methods of integer linear programming are applied to the original large-scale problem and localize the search region for solution by detection of the necessary amount of objects. At the next steps constraints imposed onto relatively small groups of objects can be considered individually, which allows to reduce significantly dimension of the problem. The key problem of estimation of the number of instances intended for generation of correct object collection and its reduction to an integer linear programming problem is investigated in detail. The performed experiments demonstrate prospectivity of the combined computational strategy and efficiency of the proposed method for verification of large-scale data models. The work is supported by RFBR (grant 13-07-00390).

The paper is addressed to an analysis of object-oriented data models specified at EXPRESS language and widely used in industrial applications. These models play important role for achievement of software interoperability and system integration in accordance with STEP standard family (ISO 10303). The examples of such models are STEP application protocols for machinery construction, automobile industry, shipbuiling, electronics, electrical engineering, systems engineering, furniture production as well as IFC (ISO 16739) model for architecture, engineering and construction, CIS/2 model for manufacturing using constructional steel work, POSC Caesar (ISO 15296) model for oil and gas producing industry. The purpose of the performed analysis is to unify representation of data integrity constraints typically used in the models by means of identification of constraint patterns. The identified patterns are specified at EXPRESS language as an unified constraint library that can be applied both on refactoring of the existing models and on development of new ones. Utilizing the constraint library users can improve clearness of the specifications, to simplify their maintenance and evolution and, on the whole, to accelerate their development. Besides, CASE tools can be effectively applied to analyze the specifications in highly automatic way. Possibility to apply the library for verification of the data models is also discussed in the paper. Rules for resolving the appropriate constraints have been proposed for each pattern. The constraint library can be recommended to industrial consortiums and technical committees that are engaged in development and standardization of the data models. The work is supported by RFBR (grant 13-07-00390).

Background: Bone tissue is a non-classical endocrine organ, which produces at least two hormones: fibroblast growth factor 23 (FGF-23) and decarboxylated osteocalcin (OC). In addition to this, recent studies demonstrate that specific proteins involved in the paracrine regulation of bone remodelling can be measured in peripheral serum samples and may serve as additional biomarkers of bone metabolism. Aims: to evaluate the serum levels of biomarkers related to endocrine and paracrine function of bone tissue in patients with Cushing’s disease (CD) and acromegaly. Materials and methods: The study was conducted according to the cross-sectional case-control type. Fasting serum samples were taken between 8–10 a.m. from patients with CD, acromegaly and age-, sex- and BMI-matched healthy volunteers and stored at -40° C. Commercially available kits for enzyme-linked immunosorbent assay (ELISA) were used to determine the serum levels of FGF-23, co-factor (co-receptor) Klotho, cathepsin K, sclerostin, P1NP. Insulin-like growth factor-1 (IGF-1) was measured by the immunochemiluminescence assay, late-night (11 p.m.) salivary cortisol (LNSC) was evaluated using the electrochemiluminescence method. Non-parametric tests (the Kruskal-Wallis test and the Mann-Whitney test) were used to assess the differences between the groups of patients. Results: The study includes 78 patients, (37.6 years old, 95% CI 34.75–40.46): 29 patients with CD (group 1), 22 – with acromegaly (group 2), and 27 healthy individuals (group 3), matched by sex, age and BMI (p = 0.432, 0.373 and 0.725 between groups, respectively). LNSC in patients with CD and IGF-1 in patients with acromegaly were significantly higher compared to the control group (p = 0.004 and p

Purpose: the authors aim to show the reality of the decision of the actual task putted by the Russian President V.V. Putin to transport builders: two times increasing construction of automobile roads and to ground fundamental principles of the Russian automobile roads network technological modernization, allowing solving the modern requirements of automobile transport.Methods: in the present study the following methods were used: systemic approach, methods of social diagnosis, comparative analysis, method of expert evaluations, and method of statistical processing of information.Results: the short characteristic of modern development and technical level of the Russian automobile roads network as the important part of the automobile roads material-technical base is presented. Realization process of the actual task putted by Russian President V.V. Putin to transport builders: two times increasing construction of automobile roads is analyzed. The reality of decision this task due to modernization roads economy material-technical base on the base of innovative technologies and progressive world experience in the field of roads construction is scientifically proved.Conclusions and Relevance: in spite of losing now in decision of the actual task putted by Russian President V.V. Putin to transport builders: two times increasing construction of automobile roads, nevertheless the real possibilities to reach the important aim still remain. It may be done only due to scientifically grounded modernization of the roads economy material-technical base on the base of innovative technologies and progressive world experience in the field of roads construction.

Purpose: the main goal of the article is to build a conceptual model for the organization of effective functioning of the points of economic and innovative growth of the region in modern conditions, taking into account regional and municipal limitations of internal and external nature, with the aim of ensuring economic security, effective interaction of subjects of the "business-power" system Taking into account the influence of institutional factors. Methods: in the present study the following methods were used: systemic approach, methods of social diagnosis, comparative analysis, method of expert evaluations, and method of statistical processing of information. Results: the short characteristic of modern development and technical level of the Russian automobile roads network as the important part of the automobile roads material-technical base is presented. Realization process of the actual task putted by Russian President V.V. Putin to transport builders: two times increasing construction of automobile roads is analyzed. The reality of decision this task due to modernization roads economy material-technical base on the base of innovative technologies and progressive world experience in the field of roads construction is scientifically proved. Conclusions and Relevance: in spite of losing now in decision of the actual task putted by Russian President V.V. Putin to transport builders: two times increasing construction of automobile roads, nevertheless the real possibilities to reach the important aim still remain. It may be done only due to scientifically grounded modernization of the roads economy material-technical base on the base of innovative technologies and progressive world experience in the field of roads construction

The article analyzes the essence, location, status, and role of the informal BRICS grouping. The authors examine and compare the different points of view on this phenomenon and believe that the comparative and economical approaches that dominate in the contemporary studies of the BRICS are unproductive. While member countries of the Association are experiencing economic slowdown or recession, BRICS is gradually becoming a political phenomenon of the global world.BRICS is considered the center of an impact of the regional leaders on three continents. A specifi c model of communication of the member countries of the BRICS and their partners is polylogue as one of the methods to solve the problem of equitable participation of all countries of the global world in the process of global governance. In the geopolitical framework of the BRICS and their partners, it is the formation of an extra-American zone of interaction, which will gradually evolve into a Global nonWestern project..