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Aim. These recommendations are developed for practitioners in order to familiarize them with modern diagnostic methods, management features and pharmacotherapy of patients with gastroesophageal reflux disease (GERD).General provisions. GERD is the most common reason for patients to visit clinics. There are esophageal and extraesophageal manifestations of GERD. Patients' complaints of heartburn and regurgitation remain the most sensitive and specific clinical manifestations of GERD. The diagnosis of GERD is established on the basis of anamnestic data, instrumental examination (detection of reflux esophagitis during upper gastrointestinal endoscopy, detection of pathological gastroesophageal reflux with 24-hour pH-metry or/and 24-hour pH-impedance monitoring). Patients with suspected GERD and the absence of erosive and ulcerative changes in the mucous membrane of the esophagus or the presence of erosive esophagitis of Grade A according to Los Angeles Classification of Gastroesophageal Reflux Disease are recommended to conduct 24-hour pH-metry on PPI off to exclude or confirm the diagnosis of GERD. Patients with extraesophageal manifestations of GERD without classic symptoms (heartburn, regurgitation) are recommended to undergo 24-hour pH-impedance monitoring with discontinuation of proton pump inhibitor therapy. When deciding on surgical treatment, all patients need to perform high-resolution esophageal manometry and 24-hour pH-impedance monitoring. Complications of GERD include bleeding, strictures, Barrett’s esophagus and esophageal adenocarcinoma. The main groups of medications used in the treatment of GERD are proton pump inhibitors (PPIs), potassium-competitive acid blockers (P-CABs), alginates, antacids, and prokinetics. PPIs are the drugs of choice in the treatment of both symptoms of gastroesophageal reflux disease and existing erosive esophagitis. Combination therapy Rebamipide with PPIs increases the effectiveness of relief of GERD symptoms, as well as reduces the frequency of relapses.Conclusion. These clinical recommendations will improve the quality of medical care for patients with GERD.

Rosacea is a chronic inflammatory dermatosis characterized by facial skin lesions such as erythema, papules, pustules, phymas, and ocular involvement. In Russia, rosacea affects 5% of the population, while in European countries it ranges from 1.5% to 10%. This review presents the pathogenesis, classification, and modern approaches to the treatment of rosacea in Russia. Although rosacea is typically managed by specialists, it is also of interest to general practitioners. The goals of rosacea treatment are to reduce symptom severity and prevent disease exacerbations, thereby extending periods of stable remission. Despite advances in understanding the molecular mechanisms of the disease, development of classification approaches, and phenotype-­specific therapy, treatment failures and severe cases of rosacea persist. In addition to timely diagnosis and differential diagnosis in therapeutic practice, it is necessary to consider the increased risk of associations between rosacea and internal organ pathologies, as well as potential drug interactions among various medications used to treat this disease.

Abstract Two different methods are used to study the existence and stability of the (1+1)-dimensional Φ4 oscillon. The variational technique approximates it by a periodic function with a set of adiabatically changing parameters. An alternative approach treats oscillons as standing waves in a finite-size box; these are sought as solutions of a boundary-value problem on a two-dimensional domain. The numerical analysis reveals that the standing wave’s energy-frequency diagram is fragmented into disjoint segments with ω n+1 < ω < ω n , where ω n = ω 0/(n + 1), n = 0, 1, 2, . . ., and ω 0 is the endpoint of the continuous spectrum (mass threshold of the model). The variational approximation involving the first, zeroth and second harmonic components provides an accurate description of the oscillon with the frequency in (ω 1, ω 0), but breaks down as ω falls out of that interval.

The article is dedicated to the problem of food allergy in children. The number of patients with this pathology continues to rise, which can be explained by multiple factors, which speaks for the relevance and the social importance of the matter. For food allergy, the causesignificant allergens are both simple and complex food proteins. Wheat is one of the most prevalent source of food allergens not only for children, but for adults too. The article contains the main information concerning the ley characteristics of this product; the protein content and the different roles of individual components in forming allergic reactions and cross activity are thoroughly investigated. The authors provide recommendations for the diagnostics and treatment of wheat protein allergy, and various difficulties in different clinical cases are examined. The article also contains main treatment approaches, which are relevant to the modern data. An individual approach in each case means regular monitoring of the main figures, preventing the negative consequences of an eliminative diet at wheat protein allergy through using specialized gluten-free products.

The review is dedicated to treatment of allergic diseases in children, particularly to the use of the 2nd generation antihistamine. It demonstrates that mediator histamine has the crucial role in pathophysiology of the allergic reaction. Antihistamines block histamine action aimed at H1 receptors by way of competitive inhibition. The 2nd generation antihistamines are the drugs of choice for the treatment of allergic diseases due to the absence of sedative effect. The review presents clinical and pharmacological description of the selective 2nd generation antihistamine cetirizine, efficacy and safety of which have been appraised in numerous long-term clinical studies in children with allergic rhinitis, urticaria and atopic dermatitis.

Relevance. Allergic pathology, particularly, pollinosis, may reduce cognitive functions in children. Objective: study effect of allergen-specific immunotherapy on cognitive functions in children with pollinosis and relation of cognitive functions dynamics to repeated ASIT courses. Patients and methods. We determined condition of cognitive functions in 97 children of 8‑17 years of age with pollinosis in comparison with their healthy peers using a psychophysiological computer complex “Psychomath”. Results. We revealed reduction in cognitive activity parameters in most children with pollinosis during remission. Concurrent persisting allergic rhinitis aggravated reducing in cognitive functions parameters. Conclusion. We confirmed positive effect of allergen-specific immunotherapy: cognitive functions improve significantly in children with pollinosis; the effect becomes more pronounced after repeated courses.

Sore throat is a common complaint, with which addresst not only to general pediatricians, but also to more narrow specialists. This complaint is predominant in acute infections of the oropharynx, such as pharyngitis and tonsillitis. Therefore the problem of treatment of such conditions is of a high importance. Imudon, the drug which considerably differs from all the other medicines used in topic therapy of pharyngitis, has been widely used and confirmed its efficacy in recent years. This drug is a polyvalent antigenic complex, containing lisates. The article represents the results of the studies, which aims were to assess efficacy and safety of this drug usage in children with chronic tonsillitis, pharyngitis, oral mucous membranes and periodontium diseases and in frequently ill children.

The article focuses on providing children with atopic dermatitis, all necessary macro-and micronutrients for good development of the body. The problem of nutrition is relevant in these patients, since they need to comply with hypoallergenic diet. The authors demonstrate the results of own research concerning vitamin provision for children with allergic diseases and correction of hypovitaminosis. It is shown that the use of multivitamin preparation not only doesn’t aggravate the disease due to the risk of allergic reactions, but contributes to the long-term remission.

Atopic dermatitis (AD) is one of the most common allergic diseases in children which is assuming ever greater medical and social importance. Risk factors of AD include gastro-intestinal tract disturbances, especially intestinal dysbiosis, which is revealed in 89–94,1% of children with atopic dermatitis. Both correlation of the dysbiosis and AD manifestations severity and increase of underlying disease treatment efficacy as a result of target influence on intestinal microflora confirm that. For many decades guidelines of atopic dermatitis treatment in children along with elimination diet, antihistamine drugs and topic medicines include enterosorbents. The most effective drugs are those ones, consisting of prebiotics and sorbents. The wide experience of prebiotic drug with sorbent action (Lactofiltrum) in complex therapy of atopic dermatitis in children is reviewed in this article.

Study of spherically symmetric time-periodic standing waves of the \( \varphi^4 \) model in a ball of finite radius was carried out based on the numerical solution of a boundary value problem on a cylindrical surface for a wide range of values of the oscillation period. The standing waves in a ball of finite radius can be considered as an approximation of weakly radiating spherically symmetric oscillons in the \( \varphi^4 \) model. Stability analysis the waves obtained is based on the calculation of the corresponding Floquet multipliers. In the paper, mathematical formulation of the problem is given, the numerical approach is described, including the method of parallel implementation of the calculation of Floquet multipliers on the computing resources of the HybriLIT platform of the Multifunctional Information and Computing Complex of the Joint Institute for Nuclear Research (Dubna). The results of the study of the space-time structure and bifurcation of coexisting standing waves of various types are presented.

Aim: to discuss current views on the clinical significance, diagnostic opportunities, and therapeutic approaches in the treatment of small intestinal bacterial overgrowth (SIBO) as an important component in the gut microbiota function assessment, to assess the awareness of physicians and the opportunities in the diagnosis and treatment of this disease in patients in the Federal districts of the Russian Federation, as well as to present the proceedings of the Expert Council held on December 16, 2023 in Moscow.Key points. SIBO is a common syndrome often associated with irritable bowel syndrome, liver cirrhosis, asthma, and congestive heart failure, being also a predictor of early death in the elderly. Today, in many regions of the Russian Federation, there are limitations for instrumental diagnosis of this disease — lack of awareness among doctors, unavailability of gas analyzers for diagnosing SIBO, lack of information about the need to diagnose SIBO in the standards of compulsory health insurance. Rifaximin is the first-line treatment due to the highest therapeutic efficacy. One of the ways to increase the efficacy of SIBO treatment is to include strain-specific probiotics in the treatment regimen. Saccharomyces boulardii CNCM I-745 is thought to be the most studied, promising probiotic. The review also presents statistical data on the issues in the diagnosis and treatment of SIBO in the regions of the Russian Federation.Conclusion. Optimization of approaches to the diagnosis and treatment of SIBO, the development of domestic gas analyzers, increasing the awareness of physicians in all regions of the Russian Federation, as well as the development and optimization of clinical recommendations appear to be necessary measures to increase the effectiveness of medical care, the duration and quality of life of the Russian population. These goals can be achieved within the framework of Federal programs under the supervision of specialized reference centers of the Ministry of Health of the Russian Federation.

Purpose: N-methyl-D-aspartate (NMDA) receptors that are expressed by T-cells modulate T-cell proliferation, cytotoxicity and cell migration toward chemokines. Several studies have shown an anti-inflammatory effect of NMDA receptor antagonists. This study compares the effect of the noncompetitive low-affinity NMDA receptor antagonist N-(2-adamantyl)-hexamethyleneimine hydrochloride (hemantane) in a topical formulation (gel) with the cyclooxygenase (COX) inhibitor diclofenac in a topical formulation (gel) in rats with arthritis induced by Freund’s Complete Adjuvant (FCA). Methods: On day 14 after an FCA injection into the left hind paw, rats with contralateral hind paw edema were selected for further investigation (29/65). They were treated with 5% hemantane gel or 1% diclofenac gel applied locally to hind paws daily for 2 weeks starting 14 days after the FCA injection. Rats with arthritis were examined hind paw edema, hyperalgesia, and motor deficits; their body weight and hematological parameters were recorded. The rats were euthanized on day 28, followed by histological examination of the ankle joint (HE stain). Results: Rats with arthritis exhibited hind paw inflammation and hyperalgesia, motor deficits, changes of hematological parameters, reduced weight gain and spleen hypertrophy. Histological examination of the ankle joint revealed degenerative-dystrophic lesions of the cartilaginous tissue, proliferative inflammation of the synovium, edema and lymphocytic/macrophage infiltration of periarticular tissues. Hemantane gel reduced hind paw edema, pain, motor deficits and histological signs of inflammation; its effect was comparable to diclofenac gel. Conclusion: Hemantane gel alleviates FCA-induced arthritis in rats, and its effect is comparable to diclofenac gel.

The use of slow-acting disease-modifying symptomatic drugs, such as bioactive concentrate from small marine fish (BCSMF, Alflutop), is considered a potential element of complex therapy for chronic non-specific back pain (CNBP).Objective: to evaluate the efficacy of the BCSMF in patients with CNBP in real-life clinical practice.Material and methods. An open observational study included 10,047 patients with CNBP (age – 58.3±14.9 years, 58.4% women) with moderate or severe pain – 60 [50; 70] mm on the visual analogue scale (VAS). All patients received a course of BCSMF medication: 1 ml intramuscular (IM) daily No. 20 or 2 ml IM every other day No. 10. 68.8 % of patients also took non-steroidal anti-inflammatory drugs. Treatment outcomes were assessed 10 days after completion of BCSMF therapy (30 days after initiation of treatment).Results and discussion. As a treatment result, the pain intensity according to the VAS decreased from 60 [50; 70] to 20 [10; 30] mm (p< 0.0001). A good response to treatment (pain reduction >50%) was observed in 73% of patients. On average, an improvement was observed on the 8th [5; 10] day of BCSMF therapy. There were no serious adverse effects associated with the use of the drug. Older age, overweight, initially more severe pain, and the presence of comorbid conditions were slightly more frequently associated with a less pronounced response to therapy.Conclusion. The use of BCSMF rapidly and effectively reduces the severity of pain and other symptoms associated with CNBP.

Research into second language (L2) reading is an exponentially growing field. Yet, it still has a relatively short supply of comparable, ecologically valid data from readers representing a variety of first languages (L1). This article addresses this need by presenting a new data resource called "MECO L2" (Multilingual Eye Movements Corpus), a rich behavioral eye-tracking record of text reading in English as an L2 among 543 university student speakers of 12 different L1s. MECO L2 includes a test battery of component skills of reading and allows for a comparison of the participants' reading performance in their L1 and L2. This data resource enables innovative large-scale cross-sample analyses of predictors of L2 reading fluency and comprehension. We first introduce the design and structure of the MECO L2 resource, along with reliability estimates and basic descriptive analyses. Then, we illustrate the utility of MECO L2 by quantifying contributions of four sources to variability in L2 reading proficiency proposed in prior literature: reading fluency and comprehension in L1, proficiency in L2 component skills of reading, extralinguistic factors, and the L1 of the readers. Major findings included (a) a fundamental contrast between the determinants of L2 reading fluency versus comprehension accuracy, and (b) high within-participant consistency in the real-time strategy of reading in L1 and L2. We conclude by reviewing the implications of these findings to theories of L2 acquisition and outline further directions in which the new data resource may support L2 reading research.

On July 3, 2023, an interdisciplinary Council of Experts The burden of COVID-19 in a heterogeneous population of immunocompromised patients post-pandemic realities was held in Moscow with leading experts in pulmonology, rheumatology, hematology, oncology, nephrology, allergology-immunology, transplantation, and infectious diseases. The aim of the meeting was to discuss the current clinical and epidemiologic situation related to COVID-19, the relevance of disease prevention strategies for high-risk patients. The experts addressed the following issues: 1) the disease burden of COVID-19 in 2023 for patients with immunodeficiency in different therapeutic areas; 2) the place of passive immunization with monoclonal antibodies as a method of COVID-19 prophylaxis among immunocompromised patients; 3) prerequisites for the inclusion of passive immunization of immunocompromised patients into routine clinical practice.

Аim: the clinical practice guidelines intended for gastroenterologists, internal medicine specialists, infectious disease specialists, general practitioners (family doctors), coloproctologists, surgeons and endoscopists present modern methods of diagnosis, prevention and treatment of C. difficile-associated disease.Key points. C. difficile-associated disease is a disease that develops when the diversity of the intestinal microbiota decreases and C. difficile excessively colonizes the colon, the toxins of which damage the intestinal muco-epithelial barrier, followed by the development of inflammation in the colon wall, with diarrhea being a characteristic clinical manifestation. The clinical presentation of the disease can vary from asymptomatic carriage, mild to moderate diarrhea that resolves on its own, to profuse watery diarrhea and pseudomembranous colitis with development of life-threatening complications. The diagnosis of C. difficile-associated disease is based on an assessment of the clinical presentation, medical history, an objective examination of the patient and laboratory stool tests. The disease severity is determined by clinical symptoms and laboratory findings. Additional diagnostic methods that are used according to indications and contribute to the assessment of severity include endoscopy of the colon and abdominal cavity imaging methods. Treatment should be initiated in cases of characteristic clinical presentation of C. difficile-associated disease and positive laboratory stool testing. The choice of drug and treatment regimen depends on the severity of the episode, the presence of complications, and whether the episode is initial, recurrent, or reinfection.Conclusion. Determination of target groups of patients for the diagnosis of clostridial infection is important in preventing overdiagnosis and subsequent unnecessary treatment. Timely diagnosis and treatment of C. difficile-associated disease help avoiding the development of life-threatening complications and improve the prognosis and quality of life of patients.

Aim. To evaluate the efficacy and safety of a combination of virus-neutralizing monoclonal antibodies MAB (casirivimab and imdevimab) in patients with mild to moderate COVID-19 with risk factors in real word settings. Materials and methods. A non-interventional non-comparative observational study with primary prospective data collection included 108 patients with mild to moderate COVID-19 (mean age 61 years), who had risk factors for developing severe disease. All patients (n=108) were treated with a combination of MAB casirivimab and imdevimab intravenous single infusion 1200 mg (600 mg of each component). The efficacy and safety of MAB were assessed at 7, 14, and 28 days after infusion. Results. Efficacy. Indications for hospitalization by day 7 from the moment of MAB administration were in 0.9% (n=1), by day 14 in 1.9% (n=2), by day 28 in 0.9% of patients; to stay in the intensive care units by the 7th day in 4.6% (n=5), by the 14th day in 0.9% (n=1), by the 28th day in 0.9% (n=1) patients. During 28 days of follow up, the need for mechanical ventilation and extracorporeal membrane oxygenation was registered in 2/108 (1.8%) patients. There were no deaths directly related to COVID-19 in the assessed cohort of patients. Safety. By the 28th day of the follow up, no adverse effects due to MAB therapy were registered. Conclusion. An analysis of the results of a non-interventional observational study summarized in this article showed the high efficacy and safety of virus-neutralizing MAB combination (casirivimab and imdevimab) in patients with mild to moderate COVID-19 with of risk factors for severe COVID-19 in real word settings.

A recent study by Hon et al. reported that a close-in planet around the red clump star, 8 UMi, should have been engulfed during the expansion phase of its parent star’s evolution. They explained the survival of this exoplanet through a binary-merger channel for 8 UMi. The key to testing this formation scenario is to derive the true age of this star: is it an old “imposter” resulting from a binary merger, or a genuinely young red clump giant? To accomplish this, we derive kinematic and chemical properties for 8 UMi using astrometric data from Gaia DR3 and the element-abundance pattern measured from a high-resolution ( R ∼ 75,000) spectrum taken by SOPHIE. Our analysis shows that 8 UMi is a normal thin-disk star with orbital rotation speed of V _ϕ = 244.96 km s ^−1 , and possesses a solar metallicity ([Fe/H] = −0.05 ± 0.07) and α -element-abundance ratio ([ α /Fe] = +0.01 ± 0.03). By adopting well-established relationships between age and space velocities/elemental abundances, we estimate a kinematic age of ${3.50}_{-2.00}^{+3.00}$ Gyr, and a chemical age of ${3.25}_{-1.50}^{+2.50}$ Gyr from [C/N] and 3.47 ± 1.96 Gyr from [Y/Mg] for 8 UMi, respectively. These estimates are consistent with the isochrone-fitting age ( ${1.90}_{-0.30}^{+1.15}$ Gyr) of 8 UMi, but are all much younger than the timescale required in a binary-merger scenario. This result challenges the binary-merger model; the existence of such a closely orbiting exoplanet around a giant star remains a mystery yet to be resolved.

The digestive organs are highly sensitive to the influence of orbital flight factors and can limit the professional activities of crew members aboard the International Space Station. Connective tissue, as a system-forming matrix of the integrative-buffer metabolic environment, is of particular relevance in space biomedicine, ensuring the functioning of internal organs under an altered gravitational stimulus. However, the adaptive mechanisms of the fibrous extracellular matrix of the gastric and intestinal connective tissue have not been fully investigated under prolonged microgravity weightlessness. Using histochemical techniques, we experimentally studied the state of collagen fibers in the specific tissue microenvironment of the gastric and intestinal membranes in C57BL/6 N mice after a 30-day space flight, subsequent 7-day ground readaptation, and in animals of the relevant control groups. The 30-day stay of laboratory animals aboard the Bion-M 1 biosatellite resulted in a reduction in the fibrous extracellular matrix of connective tissue in the studied digestive organs, excepting the gastric lamina propria. Increased fibrillogenesis was revealed in the gastrointestinal mucous membranes of animals 7 days after biosatellite landing compared with the parameters of animals in the space flight group. During the experiment with ground simulated orbital flight conditions, changes in collagen fibers were not significant compared to the vivarium control group. Thus, the results obtained evidence gravisensitivity of the fibrous extracellular matrix of the intraorgan connective tissue. This fact also highlights the necessity to further improve gastrointestinal tract-related preventive measures for astronauts during orbital flight.

Purpose. The given article is devoted to the issue of social responsibilities in the educational context. The purpose of the article is to analyze the concept of social responsibilities as one of the main professional competencies and its reflection in educational results of higher education. Methodology. The methods of descriptive and evaluative analysis and synthesis are applied. This work covers the latest research results, normative documents, cur-rent trends in the labor market, as well as issues of psychological adaptability and social responsibility of those to secure the future of the economy. The authors prove that social responsibility is crucial in the 21st century. Results. The necessary conditions for the sustainable development of modern socie-ty are economic stability and continuous professional growth of the participants of social interactions. Higher education aims to develop students’ hard skills and their soft skills, which are currently referred to as life competencies. The paper reveals the conditions that need to be created within the framework of the educational pro-cess for the graduates to meet the requirements of the labor market. The work de-scribes the tendencies and the potentials of the higher educational system to provide its graduates with appropriate career trajectories. The ongoing transformation of the Russian educational system carried out according to current requirements of the society, contributes to the relevance of this study. The results of the research can be applied in teaching process at higher educational establishments.

The paper considers the analysis of translatological trilingualism which is essential for cross-cultural exchange and translation studies. Today trilingualism is perceived as a form of multilingualism that includes a mechanism for formation and development of a language personality. The paper presents the accumulated experience of trilingual educational techniques in Russia and abroad, which was starkly demonstrated by I. Alexeeva, as well as the perspectives of their implementation into the educational process. Trilingualism is considered as a complex phenomenon that includes anthropological, social and linguistic, as well as social and cultural components. The aspect of cultures which implies the phased existence of the same text in three linguistic substances, as well as translation of literary works aimed at transfer of the works of fiction from one language to another through an intermediary language. Concurrently, the special attention is paid to the Russian language and its productive role as a cultural mediator in translation of the world literature to the languages of the peoples of Russia, which has not been thoroughly studied yet. The intermediary results of the research were presented by A. Boyarkina. The paper reveals perspectives for application of the trilingual model in order to expand the translatological functions of the artificial intelligence. The Master's programme in "Translation Theory, Cross-Cultural and Cross-Lingual Communication" implemented at Kazan Federal University, revealed by S. Takhtarova, the head of the programme, and K. Prosyukova, the coordinator of the programme, as well as other educational programmes in St. Petersburg and Almaty, carefully analysed by I. Alexeeva and A. Boyarkina, are the successful examples of trilingualism as an educational tool. To sum up, it is concluded that the interaction of three languages is able to create the effective educational environment that ensures the exchange of cultures and transmits cultural values, as well as linguistic and translation skills, formed on the basis of other two languages.

This article describes the onset of arrhythmogenic cardiomyopathy, left-dominant form, in a pediatric patient that was initially regarded as dilated cardiomyopathy. This clinical case shows issues of the disease differential diagnosis and the need of complex approach to the patient’s examination including heart magnetic resonance imaging and molecular and genetic testing.

From the outset of the conflict, discourses on the war in Ukraine have become a political arena for Chinese diplomacy and Beijing's discursive power in the world. In developing its official discourse on the conflict, Beijing has had to calibrate its communications to different external and internal factors and mobilize different strategies to promote them. Certainly linked to Russia after many years of economic and political rapprochement with Moscow, the Chinese government had to define a position. How has the Chinese discourse sought to preserve its Russian partner, knowing that there is no formal alliance between Moscow and Beijing and that economic relations between China and the West are stronger than with Russia? This article uses a qualitative approach and analyzes the evolution of Chinese media discourse by conducting a qualitative study of the publications of two Chinese newspapers, the Huanqiu Shibao and the Caixin Zhoukan, as well as by analyzing the publications of Chinese Internet users and experts on the microblogging site Weibo. The analysis highlights the notable evolution of Chinese official discourse on the war in Ukraine since the beginning of the Russian invasion. This evolution reflects both Beijing's determination to preserve its neutrality in order to reduce the impact of the crisis on its own geopolitical ambitions and economic prospects, and the change in the international context surrounding the war following its escalation in space and time.

IntroductionThe blockade of interleukine-1 (anakinra and canakinumab) is a well-known highly effective tool for monogenic autoinflammatory diseases (AIDs), such as familial Mediterranean fever, tumor necrosis factor receptor-associated periodic syndrome, hyperimmunoglobulinaemia D syndrome, and cryopyrin-associated periodic syndrome, but this treatment has not been assessed for patients with undifferentiated AIDs (uAIDs). Our study aimed to assess the safety and efficacy of canakinumab for patients with uAIDs.MethodsInformation on 32 patients with uAIDs was retrospectively collected and analyzed. Next-generation sequencing and Federici criteria were used for the exclusion of the known monogenic AID.ResultsThe median age of the first episode was 2.5 years (IQR: 1.3; 5.5), that of the disease diagnosis was 5.7 years (IQR: 2.5;12.7), and that of diagnostic delay was 1.1 years (IQR: 0.4; 6.1). Patients had variations in the following genes: IL10, NLRP12, STAT2, C8B, LPIN2, NLRC4, PSMB8, PRF1, CARD14, IFIH1, LYST, NFAT5, PLCG2, COPA, IL23R, STXBP2, IL36RN, JAK1, DDX58, LACC1, LRBA, TNFRSF11A, PTHR1, STAT4, TNFRSF1B, TNFAIP3, TREX1, and SLC7A7. The main clinical features were fever (100%), rash (91%; maculopapular predominantly), joint involvement (72%), splenomegaly (66%), hepatomegaly (59%), lymphadenopathy (50%), myalgia (28%), heart involvement (31%), intestinal involvement (19%); eye involvement (9%), pleuritis (16%), ascites (6%), deafness, hydrocephalia (3%), and failure to thrive (25%). Initial treatment before canakinumab consisted of non-biologic therapies: non-steroidal anti-inflammatory drugs (NSAID) (91%), corticosteroids (88%), methotrexate (38%), intravenous immunoglobulin (IVIG) (34%), cyclosporine A (25%), colchicine (6%) cyclophosphamide (6%), sulfasalazine (3%), mycophenolate mofetil (3%), hydroxychloroquine (3%), and biologic drugs: tocilizumab (62%), sarilumab, etanercept, adalimumab, rituximab, and infliximab (all 3%). Canakinumab induced complete remission in 27 patients (84%) and partial remission in one patient (3%). Two patients (6%) were primary non-responders, and two patients (6%) further developed secondary inefficacy. All patients with partial efficacy or inefficacy were switched to tocilizumab (n = 4) and sarilumab (n = 1). The total duration of canakinumab treatment was 3.6 (0.1; 8.7) years. During the study, there were no reported Serious Adverse Events (SAEs). The patients experienced non-frequent mild respiratory infections at a rate that is similar as before canakinumab is administered. Additionally, one patient developed leucopenia, but it was not necessary to stop canakinumab for this patient.ConclusionThe treatment of patients with uAIDs using canakinumab was safe and effective. Further randomized clinical trials are required to confirm the efficacy and safety.

Background. The role of recently discovered neurospecific peptides in the pathogenesis of acute and progressive neurologic disorders, their neuroprotective features, and possibilities to use them as markers for the course and prognosis of certain diseases have been actively studied in recent decades. However, neurospecific peptides are almost not studied in chronic residual diseases. In our study we measured the levels of neurospecific peptides and some other markers to achieve understanding of general neurophysiological trends in congenital and acquired chronic non-progressive brain pathology with reference to the selection of relevant groups — study objects. Objective. The aim of the study is to study patterns of neurospecific peptides, neurotransmitters and neuroreceptor markers distribution in the serum of children with various pathogenetic variants of chronic neuropathology. Methods. The study included children from 3 to 16 years old with different pathologies. The sample was divided into groups by pathology type: no sensory and neurological disorders, congenital sensory deficit due to mutation of genes expressed and not expressed in the brain, early acquired sensory deficit of multifactorial nature, congenital mild and severe organic disorders of central nervous system (CNS) in residual stage without baseline sensory deficit, acquired functional CNS disorders without baseline organic defect and sensory deficit. The following laboratory data (neurophysiological components) was studied: nerve growth factor, brain-derived neurotropic factor, neurotrophin-3, neurotrophin-4, neuregulin-1-beta-1, beta-secretase, sirtuin-1, synaptophysin, neuronal nitric oxide synthase, and anti-NR2 glutamate receptor antibodies. The parameters of cognitive activity, sense of vision, sense of smell, and acoustic sense were also evaluated. Results. The study included 274 participants. Neuropeptides and markers have shown a variable degree and range in the group spectrum of differences from normal levels. The most variable in the examined sample was NO-synthase, as well as levels of both neurotrophins, beta-secretase, and glutamate receptor marker. All visual deficits were associated with increased NO-synthase levels (p < 0.001). Neuroplasticity peptides (beta-secretase, neurotrophin-3 and 4) have been activated in all pathological conditions. Nerve growth factor and brain-derived neurotropic factor were specifically activated in mild organic CNS lesions (mild cognitive impairments), while neuregulin — in congenital genetically determined visual deficits. There was no specific activation of neuropeptides and NO-synthase level tended to decrease in cases of severe CNS lesions. Conclusion. The study results suggest that all types of early visual impairment are associated with increased physiological neuronal activity, and non-organic neurological functional disorders — mainly with increased physiological synaptic activity. General neuroplasticity processes were activated in all cases of visual deficits but more specific. However, more specific and well-studied processes were activated in mild organic CNS lesions, and neuroplasticity processes did not activate adequately in severe organic CNS lesions probably due to the limited neuronal and synaptic resources.

Abstract Background Medical schools were compelled to abruptly transition pre-clerkship curricula to remote learning formats due to the emergence of the Coronavirus Disease 2019 (COVID-19) pandemic. We evaluated student perceptions of remote learning, exam performance, and utilization of third-party learning resources to assess the implementation of a newly developed pandemic-appropriate physiology curriculum. Methods This was an observational study based on a survey conducted in the Spring of 2021 at the University of California, Irvine, School of Medicine (UCISOM). This study aimed to assess first (MS1) and second year (MS2) medical students’ perceptions of satisfaction, support, academic performance, and connectedness before and during the COVID-19 pandemic. The MS1 class began medical school during the first year of the COVID-19 pandemic, whereas the MS2 class did so prior to the start of the pandemic. A survey instrument was developed and validated to identify the impact remote learning had on student self-perceptions of the Medical Physiology and Pathophysiology course. Surveys were distributed to all students and responses were collected on a voluntary basis. Exam scores on a customized National Board of Medical Examiners (NBME) physiology shelf exam were also compared to objectively identify how the remote curriculum during the pandemic impacted academic performance. Results Of 204 students enrolled, 74 responses were analyzed, with 42 MS1 (40% of MS1s) and 32 MS2 (31% of MS2s) responses. Overall, MS1s and MS2s were satisfied with the curriculum they received (95 and 97% respectively) and the school’s support of their concerns (86 and 100% respectively). Notably, only 50% of MS1s felt connected to their peers, compared to 94% of MS2s. Lecture attendance and self-perception of their academic performance were similar between both classes. Interestingly, the intra-pandemic class’s NBME exam average in 2020 (60.2% ± 8.9, n = 104) was significantly higher than the pre-pandemic class average in 2019 (56.8% ± 11.3, n = 100). Both classes primarily used course materials over third-party learning resources. An additional set of survey questions distributed only to the MS1 class found that the majority of MS1s reported minimal barriers with regards to accessibility, including internet connectivity, study-conducive environments, and balancing family commitments. Overall, pre-clerkship medical students had positive perceptions of the newly developed pandemic-appropriate physiology curriculum. Conclusions Changes to the pre-clerkship physiology curriculum during the COVID-19 pandemic were met with overall satisfaction from the students and an increase in NBME scores. More attention to student connectedness is needed to improve how remote learning can be best optimized into future curricula development.

Preclinical studies showed synergic anti-tumor activity of Rituximab and Fludarabin. Comparison of efficacy of FC with FCR regimens administered in first line therapy and their influence on disease-free and overall survival in patients with B-cell lymphocytic leukemia were the main goals of this retrospective study. It has been demonstrated that inclusion of Rituximab into the FC regimen improves outcome of patients with B-cell lymphocytic leukemia without significant increase of toxicity.

Abstract Background Little is known about the disposition to autoimmune diseases (ADs) among children diagnosed with JIA. In this study, we provide a comprehensive overview of the prevalence of and factors associated with ADs in parents of children with juvenile idiopathic arthritis (JIA). Methods Prevalence rates of ADs and 95% Poisson confidence intervals were calculated for parents of JIA patients from the international Pharmachild registry and compared with general population prevalence rates as reported in the literature. Demographic, clinical and laboratory features were compared between JIA patients with and without a family history of AD using χ2 and Mann-Whitney U tests. Results Eight thousand six hundred seventy three patients were included and the most common familial ADs were psoriasis, autoimmune thyroid disease, rheumatoid arthritis and ankylosing spondylitis. The prevalence of several ADs was higher in parents of the included JIA patients than in the general population. Clinical Juvenile Arthritis Disease Activity Scores at study entry and last follow-up were not significantly different between patients with (n = 1231) and without a family history of AD (n = 7442). Factors associated with familial AD were older age at JIA onset (P

Demonstration of generation of terahertz structured light in a form of configurable Airy beam for imaging aims and 2D materials inspection using exclusively flat silicon diffractive optics.

Social stereotypes are extremely generalized and simplified views about various subjects and social phenomena that have evolved in the course of society development. Proverbs are also generalized statements that have been formulated by people throughout the history. The aim of our research is to prove that the proverbs are actually the reflection of social stereotypes that have long been affecting social relations. Using the method of continuous sampling we have selected the English proverbs that contain the main categories of existing stereotypes: gender, age, ethnic and professional stereotypes. We have studied the most wide-spread stereotypes about men and women, elderly people, popular occupations as well as some stereotyped notions of the British about themselves and have chosen the proverbs illustrating these generalized beliefs. We have shown that the laconic, metaphoric and memorable form of proverbs facilitates their rooting in the peoples consciousness and passing them on practically unchanged from generation to generation. Statistical and comparative analysis made it possible to group the proverbs on the basis of stereotype categories and to find out their percentage ratio. The proverbs containing gender stereotypes appear to be most numerous with the prevailing number of sayings about women. Age stereotypes reflected in the proverbs are mostly related to elderly people. Professional stereotypes embrace a small number of occupations and those few are most often of negative character. Ethnic stereotypes encountered in the proverbs represent the British most favorably. The relevance of the paper lies in the fact that the study of stereotypes as reflected in the proverbs would contribute to making people give up stereotyped thinking in favour of acquiring their own attitudes and viewpoints.

Targeted treatment with somatostatin analogues (SA) in acromegaly and neuroendocrine neoplasms may have some benefits compared to curative treatments, because these agents decrease excessive hormone secretion and exert a tumor-suppressive effect. Monotherapy and combination therapy with SA is well tolerated and bears no risk of debilitating iatrogenic complications. In acromegaly caused by somatotropin producing pituitary tumor, first generation SA are treatment of choice after non-radical adenomectomy, as well as in the cases when patients reject surgery. Treatment efficacy depends on the pathomorphological types of somatotropic tumors, which are different in their receptor phenotype, clinical scenario and proliferative activity. The first generation SA are successfully used for medical treatment of other pituitary tumors (thyrotropic, corticotropic, gonadotropic, lactotropic with resistance to dopamine agonists), as well as for adjuvant therapy of neuroendocrine and non-endocrine neoplasms and elimination of various gastrointestinal disorders. The anti-secretory and anti-tumor effects of SA have been proven for gastroenteropancreatic tumors (carcinoid syndrome, vipomas, gastrinomas, insulinomas, glucagonomas, somatostatinomas). Targeted selection of patients for treatment with first generation SA based on the receptor phenotypes of malignant cells would facilitate more rapid achievement of biochemical remission, improvement of quality of life and survival.

Introduction. The research results obtained through the analysis of different varieties of Rhodiola rosea rhizomes and roots using high-performance thin layer chromatography (HPTLC), grown in the Saint-Petersburg State Chemical-Pharmaceutical University (SPCPU) medicinal plants nursery garden, are represented.Aim. To carry out a comparative analysis of Rhodiola rosea rhizomes and roots samples, grown in the SPCPU medicinal plants nursery using HPTLC.Materials and methods. HPTLC analysis was performed on a CAMAG device (Switzerland), using MERCK HPTLC silica gel 60 F 254, 20 × 10 cm plates. Extracts were obtained from raw materials using an ultrasonic bath "Sapphire-4.0 TTC" (Russia). The Rhodiola rosea rhizomes and roots were harvested in the SPCPU medicinal plants nursery garden (Leningrad Region, Vsevolozhsk district, Priozerskoe Highway, 38 km) in August 2019.Results and discussion. In the course of the research, extracts from Rhodiola rosea rhizomes and roots were obtained using 70 % ethyl alcohol and methyl alcohol as extractants. The extracts were investigated by HPTLC in ethyl acetate – methanol – water – formic acid (77 : 13 : 10 : 2) solvent system. After scanning densitometric analysis at 254 nm, the much better separation of methanol extracts in this solvent system was found than ethanol extracts. The densitograms of individual tracks were compared with each other in order to identify samples of Rhodiola rosea rhizomes and roots with a higher biologically active compounds content. As a result of the comparison of 18 samples tracks of the Rhodiola rosea rhizomes and roots (the extractant was ethyl alcohol 70 %), samples № 6 and 17 have been proposed as promising for further research and cultivation.Conclusion. As a result of the analysis of alcohol extracts from Rhodiola rosea rhizomes and roots by HPTLC, the samples 6 (Tomsk, Russia) and 17 (Valla Di Aposta/Hirvos varieties, country of origin – Italy/Finland) were found to have a higher content of biologically active compounds.

Non-bacterial osteomyelitis (NBO) is a rare chronic inflammatory bone disease related to immune system dysregulation. This disease belongs to a family of autoinflammatory diseases. It often coexists with other TNF-α-mediated immune-mediated diseases such as juvenile idiopathic arthritis (JIA) and inflammatory bowel diseases. Previously, interleukin-1-driven inflammation was described predominantly in monogenic cases of NBO, such as DIRA syndrome or Majeed syndrome. However, the association between NBO and JIA with systemic onset (soJIA) has not been described yet.Herein, we describe the cases of two patients with soJIA with inflammatory bone lesions wherein canakinumab (anti-interleukin-1β antibodies) caused remission. Case descriptionsPatient 1–A 6-month-old boy with typical soJIA suffered a destruction of the 7th to 9th ribs and the left pubic bone. Antibiotics, IVIG, and cyclosporine proved ineffective. Corticosteroids were effective, but due to the factor of corticosteroid dependence, which has some disadvantages, canakinumab with a dosage of 4 mg/kg was initiated every 4 weeks, which completely controlled the disease and allowed to taper corticosteroids.Patient 2—A 2-year-old girl developed chronic non-bacterial osteomyelitis of the 5th rib 2 months after taking corticosteroids prescribed for typical soJIA. She underwent surgical debridement removal, and several courses of antibiotics proved ineffective. She developed macrophage activation syndrome, following which anakinra was prescribed, which resulted in only temporary improvement. Therefore, this drug was switched to canakinumab, which caused corticosteroid-free remission.ConclusionThis is the first description of a rare association of soJIA with inflammatory bone lesions with the proven efficacy of IL-1 blockade. The association of two autoinflammatory conditions should indicate IL-1-driven mechanisms and a possible genetic basis. Follow-up genetic and functional studies are required to better understand the pathogenesis of such overlapping diseases.

A systematic monitoring of the hydrosphere is important and necessary to maintain a good ecological status of Lake Baikal. The article presents the results of a five-year monitoring of the groundwater and surface waters quality in Listvyanka settlement. The goal is to determine the contamination level of drinking water supply system. In the field studies, portable measurement devices were used for monitoring temperature, pH, Eh, electrical water conductivity and water levels in wells, and water samples were taken for a complete chemical analysis. The analysis of the macrocomponent composition of water was carried out by various methods (flame photometry, volumetric titration, weight method, colorimetry) at the Center for Geodynamics and Geochronology of the Institute of the Earth’s Crust SB RAS (Irkutsk); the trace element composition was determined by the ICP MS method on the Element-2 device (Finnigan MAT, Germany) at the Institute of Geochemistry SB RAS (Irkutsk); microbiological analysis of water samples was performed at the Irkutsk Interregional Veterinary Laboratory; the analysis of isotope characteristics (δ 18O and δD) of water samples was performed in the Laboratory of Hydrogeology of the Institute of the Earth’s Crust SB RAS (Irkutsk) on a Picarro L2140-i gas analyzer.The results obtained indicate a change in macrocomponent composition of waters and an uneven distribution of pollutants over the area. The content of 42 trace elements in groundwater and river waters generally does not exceed the regulatory requirements for drinking water; the exceptions are Fe and Mn. Ten wells do not meet the sanitary and epidemiological rules and norms SanPiN 2.1.4.1074-01. The main sources of groundwater pollution are leaking septic tanks of numerous hotel complexes located in the valleys and on the valley slopes. The processes of water pollution and restoration of natural regime of water are of different intensity. For groundwater and river waters, there were determined the relative concentrations of stable isotopes of hydrogen and oxygen (δD and δ18О), and δD=5.5307·δ18 O–31.815 relationship and the deuterium excess values were obtained. Characteristics δD and δ18 O are the bases of the isotope database for the aquatic environment of Listvyanka settlement.