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Over recent years, many researchers have supported the autoimmune theory of sarcoidosis. The presence of uncontrolled inflammatory response on local and system levels in patients with sarcoidosis did not define that the immunoregulatory mechanisms could be affected. The aim of this study was to evaluate the distribution and the disturbance circulating Treg cell subsets in the peripheral blood in patients with sarcoidosis. Materials and methods: A prospective comparative study was performed in 2016–2018 (34 patients with sarcoidosis (men (67.6%), women (32.3%)) were examined). Healthy subjects—the control group (n = 40). The diagnosis of pulmonary sarcoidosis was performed according to the standard criteria. We used two ten-color combinations of antibodies for Treg immunophenotyping. The first one contained CD39–FITC, CD127–PE, CCR4–PE/Dazzle™ 594, CD25–PC5.5, CD161–PC7, CD4–APC, CD8–APC–AF700, CD3–APC/Cy7, HLA–DR–PacBlue, and CD45 RA–BV 510™, while the second consisted of CXCR3–Alexa Fluor 488, CD25–РЕ, CXCR5–РЕ/Dazzle™ 594, CCR4–PerСP/Сy5.5, CCR6–РЕ/Cy7, CD4–АPC, CD8 АPC–AF700, CD3–АPC/Cy7, CCR7–BV 421, and CD45 RA–BV 510. The flow cytometry data were analyzed by using Kaluza software v2.3. A statistical analysis was performed with Statistica 7.0 and GraphPad Prism 8 software packages. Results of the study: Primarily, we found that patients with sarcoidosis had decreased absolute numbers of Treg cells in circulation. We noted that the level of CCR7-expressing Tregs decreased in patients with sarcoidosis vs. the control group (65.55% (60.08; 70.60) vs. 76.93% (69.59; 79.86) with p < 0.001). We noticed that the relative numbers of CD45RA–CCR7+ Tregs decreased in patients with sarcoidosis (27.11% vs. 35.43%, p < 0.001), while the frequency of CD45 RA–CCR7– and CD45RA+ CCR7– Tregs increased compared to the control group (33.3% vs. 22.73% and 0.76% vs. 0.51% with p < 0.001 and p = 0.028, respectively). CXCR3-expressing Treg cell subsets—Th1-like CCR60078CXCR3+ Tregs and Th17.1-like CCR6+ CXCR3+ Tregs—significantly increased in patients with sarcoidosis vs. the control group (14.4% vs. 10.5% with p < 0.01 and 27.9% vs. 22.8% with p < 0.01, respectively). Furthermore, the levels of peripheral blood EM Th17-like Tregs significantly decreased in the sarcoidosis group vs. the control group (36.38% vs. 46.70% with p < 0.001). Finally, we found that CXCR5 expression was increased in CM Tregs cell subsets in patients with sarcoidosis. Conclusions: Our data indicated a decrease in circulating Tregs absolute numbers and several alterations in Treg cell subsets. Moreover, our results highlight the presence of increased levels of CM CXCR5+ follicular Tregs in the periphery that could be linked with the imbalance of follicular Th cell subsets and alterations in B cell, based on the immune response. The balance between the two functionally distinct Treg cell populations—Th1-like and Th17-like Tregs—could be used in sarcoidosis diagnosis and the determination of prognosis and disease outcomes. Furthermore, we want to declare that analysis of Treg numbers of phenotypes could fully characterize their functional activity in peripherally inflamed tissues.

В статье анализируются и комментируются результаты очередного опроса российских предприятий реального сектора, проведенного Институтом народнохозяйственного прогнозирования РАН. Приведены мнения предприятий об остроте различных макроэкономических проблем в России. Представлены оценки предприятий по поводу качества антикризисной политики государства в период пандемии. Отражена информация взаимоотношениях российских предприятий и банков. Исследована ситуация с налоговой нагрузкой предприятий. Рассмотрена потребность предприятий в рабочей силе и трудовых мигрантах. Оценен потенциал прироста выпуска без дополнительных инвестиций. Представлены взгляды российских предприятий на ресурсо- и энергосбережение, а также на глобальные цели устойчивого развития. Отражены данные о действиях предприятий в сфере экологического страхования.

Currently, sarcoidosis remains one of the diseases with unknown etiology, which significantly complicates its diagnosis and treatment. Various causes of sarcoidosis have been studied for many years. Both organic and inorganic trigger factors, provoking the development of granulomatous inflammation are considered. However, the most promising and evidence-based hypothesis is the development of sarcoidosis as an autoimmune disease, provoked by various adjuvants in genetic predisposed individuals. This concept fits into the structure of the autoimmune/inflammatory syndrome, induced by adjuvants (ASIA) that was proposed in 2011 by Professor Shoenfeld Y. In this paper, the authors reveal the presence of major and minor ASIA criteria for sarcoidosis, propose a new concept of the course of sarcoidosis within the framework of ASIA, and point out the difficulties in creating a model of the disease and the selection of therapy. It is obvious that the data obtained not only bring us closer to understanding the nature of sarcoidosis, but also potentiate new studies confirming this hypothesis by obtaining a model of the disease.

Sarcoidosis and tuberculosis share several similar clinical and pathogenic characteristics that make some researchers consider a common pathogenesis for these diseases. Human leukocyte antigen (HLA) genotypes are studied both in sarcoidosis and tuberculosis patients, but to our knowledge, there are no comparative studies of genetic predisposition for sarcoidosis and tuberculosis development. The aim of this review was to analyse the relationship between HLA genotypes and the development of sarcoidosis and tuberculosis. Original and review articles published in various online databases from 1960 to 2019 were studied. The search results showed opposite effects of the HLA genotypes on predisposition to sarcoidosis or tuberculosis. It was revealed that the genotypes predisposing to the development of sarcoidosis (HLA-DRB1*03/07/15) have protective properties against the development of tuberculosis. Moreover, genotypes causing the development of tuberculosis (HLA-DRB1*04) have a protective effect on the development of sarcoidosis. The results of this narrative review of the literature may allude to the existence of genetic predispositions that lead to the development of an antibacterial or autoimmune response to mycobacteria., The HLA-DRB1*03/07/15 genotypes predispose to the development of sarcoidosis and have protective properties against the development of tuberculosis, while the HLA-DRB1*04 genotype has an opposite effect on the development of these diseases https://bit.ly/2Tl2rj1

Sarcoidosis is a systemic granulomatous disease that develops due to the Th1, Th17 and Treg lymphocytes disturbance. There is an assumption, that B cells and follicular T-helper (Tfh) cells may play an important role in this disorder, as well as in several other autoimmune diseases. The aim of this study was to determine CD19+ B cells subset distribution in the peripheral blood and to define disturbance in the circulating Tfh cells subsets in patients with sarcoidosis. The prospective comparative study was performed in 2016–2018, where peripheral blood B cell subsets and circulating Tfh cell subsets were analyzed in 37 patients with primarily diagnosed sarcoidosis and 35 healthy donors using multicolor flow cytometry. In the results of our study we found the altered distribution of peripheral B cell subsets with a predominance of “naïve” (IgD + CD27−) and activated B cell (Bm2 and Bm2′) subsets and a decreased frequency of memory cell (IgD+ CD27+ and IgD− CD27+) in peripheral blood of sarcoidosis patients was demonstrated. Moreover, we found that in sarcoidosis patients there are increased levels of B cell subsets, which were previously shown to display regulatory capacities (CD24+++ CD38+++ and CD5 + CD27−). Next, a significantly higher proportion of CXCR5-expressing CD45RA − CCR7+ Th cells in patients with sarcoidosis in comparison to the healthy controls was revealed, that represents the expansion of this memory Th cell subset in the disease. This is the first study to demonstrate the association between the development of sarcoidosis and imbalance of circulating Tfh cells, especially CCR4− and CXCR3-expressing Tfh subsets. Finally, based on our data we can assume that B cells and Tfh2- and Tfh17-like cells – most effective cell type in supporting B-cell activity, particularly in antibody production – may be involved in the occurrence and development of sarcoidosis and in several other autoimmune conditions. Therefore, we can consider these results as a new evidence of the autoimmune mechanisms in the sarcoidosis development.

Immunological testing for tuberculosis has been one of the most rapidly developing areas in the last decade. A new-generation immunological skin test, Diaskintest (DST), has been developed in the Russian Federation and successfully implemented into clinical practice since 2009. This article presents the results of a meta-analysis of publications reporting data on the use of the recombinant tuberculosis allergen DST (n = 121) from 2009 to 2019 included in Russian and international databases. The analysis included a total of 61 papers consistent with the study design, which cumulatively presented the results of 3,777,083 patients tested with DST (83.0%). The obtained data showed that the overall diagnostic sensitivity of the test in this population, regardless of age, was 86.0%, with 98.0% negative results. It was found that the intensity of the immune response of tuberculosis patients to specific ESAT-6 and CFP-10 antigens of DST may depend on the biological properties of the pathogen characteristic to various Mycobacterium tuberculosis genotypes, tuberculosis severity, and the presence of concomitant diseases. These factors are more prevalent in the adult population. In children, however, the test sensitivity reaches 100%. The proportion of positive DST results in HIV-positive patients tested for tuberculosis was 60.0%. The analysis showed that the accuracy (overall validity) of DST was 95.1% in the total studied population (95% confidence interval [CI]: 95.06–95.1) and 92.4% in HIV-positive patients (95% CI: 91.9–92.7).

Desirable changes in the biochemical composition of food plants is a key outcome of breeding strategies. The subsequent localization of nutritional phytochemicals in plant tissues gives important information regarding the extent of their synthesis across a tissue. We performed a detailed metabolomic analysis of phytochemical substances of grains from

Sarcoidosis (SC) is a granulomatous disease of an unknown origin. The most common SC-related neurological complication is a small fiber neuropathy (SFN) that is often considered to be the result of chronic inflammation and remains significantly understudied. This study aimed to identify the clinical and histological correlates of small fiber neuropathy in sarcoidosis patients. The study was performed in 2018–2019 yy and included 50 patients with pulmonary sarcoidosis (n = 25) and healthy subjects (n = 25). For the clinical verification of the SFN, the “Small Fiber Neuropathy Screening List” (SFN-SL) was used. A punch biopsy of the skin was performed followed by enzyme immunoassay analysis with PGP 9.5 antibodies. Up to 60% of the sarcoidosis patients reported the presence of at least one complaint, and it was possible that these complaints were associated with SFN. The most frequent complaints included dysfunctions of the cardiovascular and musculoskeletal systems and the gastrointestinal tract. A negative, statistically significant correlation between the intraepidermal nerve fiber density (IEND) and SFN-SL score was revealed. In patients with pulmonary sarcoidosis, small fiber neuropathy might develop as a result of systemic immune-mediated inflammation. The most common symptoms of this complication were dysautonomia and mild sensory dysfunction.

The measures taken against tuberculosis (TB) in recent years in the Russian Federation have been highly effective. Unfortunately, the COVID-19 pandemic may seriously undermine the progress that has been made in the fight against TB. The aim of this study was to assess changes in the epidemiological rates of tuberculosis in the Russian Federation before and after the COVID-19 pandemic. Materials and methods. The analysis was conducted by considering the main epidemiological indicators of tuberculosis, according to the federal statistics for the period from 2017 to 2021. The parameters were estimated according to the data received from 11 areas in the North-Western region. Statistical analysis was carried out using the free software computing environment R (v.3.5.1) and the commercial software package Statistical Package for the Social Sciences (SPSS Statistics for Windows, version 24.0, IBM Corp., 2016). Research results. We found a positive correlation between the incidence among the overall population and the incidence among children aged 0–17, inclusively (r = 0.55 in 2017, r = 0.60 in 2020, and r = 0.53 in 2021). Along with the received regularities, a different trend is shown in the data analysis of general incidence and health X-ray examination for tuberculosis among the general population. The correlation has decreased threefold from 2017 (r = 0.72) to 2020 (r = 0.32); this negative trend might be the result of factors such as the quality of X-ray screening examinations among the general population, and the reduced assessment objectivity of the tuberculosis incidence rate. Conclusions. In assessing the correlation between general incidence and incidence in children under 17 years of age, as well as between incidence and mortality in the Russian Federation, a positive correlation was found with an increasing trend. Such a discrepancy might be due to decreases in the occupational health examination coverage among the general population. Therefore, in the years ahead, we can expect epidemiological indicators to increase incidence and mortality, including child mortality, associated with the insufficient detection of tuberculosis among the population during the COVID-19 pandemic.

Immunological testing for tuberculosis has been one of the most rapidly developing areas in the last decade. A new-generation immunological skin test, Diaskintest (DST), has been developed in the Russian Federation and successfully implemented into clinical practice since 2009. This article presents the results of a meta-analysis of publications reporting data on the use of the recombinant tuberculosis allergen DST (n = 121) from 2009 to 2019 included in Russian and international databases. The analysis included a total of 61 papers consistent with the study design, which cumulatively presented the results of 3,777,083 patients tested with DST (83.0%). The obtained data showed that the overall diagnostic sensitivity of the test in this population, regardless of age, was 86.0%, with 98.0% negative results. It was found that the intensity of the immune response of tuberculosis patients to specific ESAT-6 and CFP-10 antigens of DST may depend on the biological properties of the pathogen characteristic to various Mycobacterium tuberculosis genotypes, tuberculosis severity, and the presence of concomitant diseases. These factors are more prevalent in the adult population. In children, however, the test sensitivity reaches 100%. The proportion of positive DST results in HIV-positive patients tested for tuberculosis was 60.0%. The analysis showed that the accuracy (overall validity) of DST was 95.1% in the total studied population (95% confidence interval [CI]: 95.06-95.1) and 92.4% in HIV-positive patients (95% CI: 91.9-92.7).

Take-Home Message.This study provides a new diagnostic index based on the antibodies to mutated citrullinated vimentin concentration and the level of different B subsets. Determination of index over 5 Units proved to be characteristic of sarcoidosis, what might help to differentiate SD from TB.Abstract. In some cases there is a problem of differential diagnosis of sarcoidosis(SD) and tuberculosis(TB)because of the similarities in clinical, X-ray and laboratory features. The aim of this study was to search for new differential diagnostic criteria for sarcoidosis and tuberculosis by calculating the index, based on the level of autoantibodies to modified citrullinated vimentin (anti-MCV) and the level of B-cell subpopulations. These parameters were measured in patients with sarcoidosis (n = 93), tuberculosis (n = 40) and healthy donors (n = 40) using the ELISA and cytometry. The absence of a statistically significant difference when comparing the level of anti-MCV, the number of B-cells in SD and TB suggests that these changes may be characteristic of granulomatous diseases. The use of the formula Ds=([B-naïve%]\[B-memory%])*([B-CD38%]+[B-CD5%])/[anti-MCV] might allow to differentiate SD with an increase in the calculated index of more than 5 units with a sensitivity of 80.00% and specificity of 93.10% (AUC = 0.926).

Sarcoidosis (SC) is the granulomatous disease of an unknown origin, where the differential diagnosis with tuberculosis (TB) is challenging and vital for patients’ prognosis. The common neurological complication in SC is a small fiber neuropathy (SFN), that is considered to be the result of the chronic inflammation, and remains significantly understudied. There is no reliable data, whether such complication is observed in TB patients, where the systemic inflammation is also described. Aim: To identify the clinical and histological correlates of the small fiber neuropathy in sarcoidosis and tuberculosis patients.Materials and methods. A study was performed in 2018 – 2019 years and included 71 patients with pulmonary sarcoidosis (n=25), pulmonary tuberculosis (n=21), and healthy subjects (n=25). For the clinical verification of the SFN, the “Small fiber neuropathy screening list” (SFN-SL) was used. A punch biopsy of the skin was performed followed by the enzyme immunoassay analysis with PGP 9.5 antibodies.Results of the study: Up to 60% of sarcoidosis patients and 19% tuberculosis patients report the presence of at least one complaint, which may be associated with SFN. The most frequent complaints included dysfunctions of the cardiovascular, musculoskeletal system and gastrointestinal tract. A negative, statistically significant correlation between the intraepidermal nerve fiber density (IEND) and SFN-SL score was revealed in both groups (Spearman coefficient, r = -0.3508, p = 0.0102, and r = -0.7382, p = 0.0064, respectively). Wherein, the density of small nerve fibers in the patients with pulmonary sarcoidosis was lower, compared to the patients with tuberculosis (Mann-Whitney test, p = 0.0047). Conclusion: In patients with pulmonary sarcoidosis, small fiber neuropathy may develop as a result of systemic immune-mediated inflammation. The most common symptoms of this complication were dysautonomia and mild sensory dysfunction. Wherein, in tuberculosis patients clinical and histological symptoms of the small fiber neuropathy were subsequently less prominent, which may represent the difference between the autoimmune and bacterial inflammation. The validated questionnaires and histologic verification of the diagnosis help to establish the severity of neuropathy of small fibers, to determine the prognosis, to plan the treatment strategн, and also may allude the possibility for the additional criteria of differential diagnosis between two diseases.

Desirable changes in the biochemical composition of food plants is a key outcome of breeding strategies. The subsequent localization of nutritional phytochemicals in plant tissues gives important information regarding the extent of their synthesis across a tissue. We performed a detailed metabolomic analysis of phytochemical substances of grains from Zea mays L. (var. Pioneer) by tandem mass spectrometry and localization by confocal microscopy. We found that anthocyanins are located mainly in the aleurone layer of the grain. High-performance liquid chromatography in combination with ion trap tandem mass spectrometry revealed the presence of 56 compounds, including 30 polyphenols. This method allows for effective and rapid analysis of anthocyanins by plotting their distribution in seeds and grains of different plants. This approach will permit a more efficient screening of phenotypic varieties during food plant breeding.

Post COVID-19 Syndrome (PCS) is a complex of various symptoms developing a month or more after the acute phase of the disease. The cases of PCS development among patients with asymptomatic/mild forms are frequently reported; however, the pathogenesis of PCS in this group of patients is still not completely clear. The publications about COVID-19 which were published in online databases from December 2019 to September 2021 are analyzed in this review. According to the analysis, PCS develops on average in 30–60% of patients, mainly among women. Fatigue, shortness of breath, cough, and anosmia were reported as the most common symptoms. The possible association between the described PCS symptoms and brain damage was revealed. We assume the possibility of an alternative course of COVID-19, which develops in genetically predisposed individuals with a stronger immune response, in which it predominantly affects the cells of the nervous system, possibly with the presence of an autoimmune component, which might have similarity with chronic fatigue syndrome or autoimmune disautonomia. Thus, the gender (female) and the presence of anosmia during an asymptomatic or mild course of the disease can be predictive factors for the development of PCS, which can be caused by autoimmune damage to neurons, glia, and cerebral vessels.

Sarcoidosis and tuberculosis have many clinical and laboratory similarities, which allowed researchers to assume the presence of common pathogenetic mechanisms in the development of both diseases. Recently, much attention has been paid to investigate the autoimmune origins in these pathologies. The aim of this study is to find out the characteristics of the autoinflammatory immune response in sarcoidosis and tuberculosis. In patients with sarcoidosis (n = 93), tuberculosis (n = 28), and in healthy donors (n = 40), the serum anti-MCV concentration was measured by ELISA, and B cell subpopulations were analyzed by flow cytometry. Based on the results obtained, the formula ([B-naive%]\[B-memory%]) * ([B-CD38%] + [B-CD5%]) / [anti-MCV] was described. The increase in the calculated index by more than 5 units with a sensitivity of 80.00% and a specificity of 93.10% (AUC = 0.926) suggest the presence of the autoimmune component, which is more typical for sarcoidosis, rather than tuberculosis patients and may serve as a diagnostic criterion.

Currently such factors as the use of heavier feedstocks, permanent strengthening of requirements to oil and gas product quality, introduction of technical regulations for oil products, which, in turn, necessitate the development of new technologies and catalysts, have a great influence on the global oil-refining and petrochemical industry development. Recently, a special attention is given to the development of new catalysts and processes for producing middle distillate fuels suitable for cold and arctic climatic conditions. Catalytic hydrodewaxing and isodewaxing processes are the most efficient in this field. Research into controlling a functional structure of catalysts and creation of catalytic systems based on zirconium dioxide modified by tungstate anions are of outstanding interest. The trend of the use of heavier petroleum feedstocks and the need to improve the oil conversion level demand will be based on destruction of high-molecular-weight compound structures with producing light and middle cuts. So, the most important processes for heavy oil residue conversion are those enabling to control transformations of resinous-asphaltenic materials by using nanoscale catalytic systems. One of the examples of the industrial implementation of technologies using suspended catalysts is the hydroconversion process implemented currently at AO TANECO (lisencer: TIPS RAS; general designer: OAO VNIPIneft).

Introduction: Patients with sarcoidosis (SC) and tuberculosis (TB) can develop a small fiber neuropathy (SFN), that is worsening the prognosis. Aim: To investigate the clinical manifestation of SFN in patients with SC and TB. Materials and Methods: In 2018-19, patients with histologically verified pulmonary SC (17 men, 5 women, aged 33.4±8.5 years), 16 patients with pulmonary TB in the pre-treatment period (9 men, 10 women, aged 36.6±9.3 years) and 73 healthy subjects (HS, 43 men, 30 women, aged 53,5±13,92 years) were included. A complete neurological investigation was performed. The questionnaire “Small fiber neuropathy screening list in sarcoidosis” (SFN-SL) was used as a validated test for the SFN evaluation. Statistical analysis was performed with Statistica 8.0 (StatSoft, Inc., USA). Differences were significant at p Results and Discussion: The average score for SFN-SL scale in patients with SC was 2.0 (0;7.3) points, 15/67.9% of them described symptoms of SFN. The majority of patients with TB had no SFN complains (average score 0.2 (0;0.4) points), only 4/21% had typical neurologic symptoms. HS had 0 (0;0) points, 1/1.4% had SFN complaints. Patients with SC had higher SFN scores in comparison with TB (p=0.001) and HS (p Conclusion: In patients with SC the manifestation of neuropathy of small fibers was described more frequent, that requires verification and prescription of therapy. TB patients had more frequent SFN symptoms than HS, that may require immunological studies.

In the last 30 years, improvement of diagnostic methods enabled routine evaluation of small A-delta and C nerve fibers impairment, which results with the clinical condition known as a small-fiber neuropathy (SFN). This syndrome develops as a result of metabolic, toxic, immune-mediated, or genetic factors. The main clinical features include neuropathic pain and autonomic disturbance, which are occasionally disclaimed due to outstanding fatigue, daily performance decline, anxiety, and depression. As clinical, neurological, nerve conduction, and electromyography studies are commonly normal, diagnosis often depends on the finding of decreased intra-epidermal density of nerve fibers, per skin biopsy. This review highlights the etiology, clinical, diagnostic aspects, and SFN treatment.