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Over the past decade, mRNA-based therapy has displayed significant promise in a wide range of clinical applications. The most striking example of the leap in the development of mRNA technologies was the mass vaccination against COVID-19 during the pandemic. The emergence of large-scale technology and positive experience of mRNA immunization sparked the development of antiviral and anti-cancer mRNA vaccines as well as therapeutic mRNA agents for genetic and other diseases. To facilitate mRNA delivery, lipid nanoparticles (LNPs) have been successfully employed. However, the diverse use of mRNA therapeutic approaches requires the development of adaptable LNP delivery systems that can control the kinetics of mRNA uptake and expression in target cells. Here, we report effective mRNA delivery into cultured mammalian cells (HEK293T, HeLa, DC2.4) and living mouse muscle tissues by liposomes containing either 1,26-bis(cholest-5-en-3β-yloxycarbonylamino)-7,11,16,20-tetraazahexacosane tetrahydrochloride (2X3) or the newly applied 1,30-bis(cholest-5-en-3β-yloxycarbonylamino)-9,13,18,22-tetraaza-3,6,25,28-tetraoxatriacontane tetrahydrochloride (2X7) cationic lipids. Using end-point and real-time monitoring of Fluc mRNA expression, we showed that these LNPs exhibited an unusually delayed (of over 10 h in the case of the 2X7-based system) but had highly efficient and prolonged reporter activity in cells. Accordingly, both LNP formulations decorated with 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[amino(polyethylene glycol)-2000] (DSPE-PEG2000) provided efficient luciferase production in mice, peaking on day 3 after intramuscular injection. Notably, the bioluminescence was observed only at the site of injection in caudal thigh muscles, thereby demonstrating local expression of the model gene of interest. The developed mRNA delivery systems hold promise for prophylactic applications, where sustained synthesis of defensive proteins is required, and open doors to new possibilities in mRNA-based therapies.

The digitalization of the high-tech economy is complicated due to several issues. One can mention non-synchrony and imbalance in the development of industrial enterprises and their integrations; changes in the elements and relations between enterprises and the external environment; as well as contradictions between the actors. Therefore, a new institutional system for industrial integrations needs to be formed. This article proposes a concept and scenario of the institutional change needed to bolster industrial integrations in the digital economy. The structural logic and algorithm of the process provides for the gradual progress through seven phases of institutional transformation. The authors have developed an institutional change management platform for strategic transformation, the core of which is a decision-making system. The platform supports the management of digital and material business processes of industrial integrations. The conceptual approach is based on a comparison of the life cycles of enterprises and their markets. The article proposes a methodology for assessing the readiness of industrial integrations to implement institutional change strategies using modified Shewhart control charts. The methodology is based on a two-criterion approach to the analysis of finances, production reserves, human resources, organizational structures, management technologies, corporate institutions, and a personnel motivation system. This approach allows determining the level of compliance of the resources available with the requirements of the transformation strategy implementation plan. The methodology has been tested at 14 enterprises functioning as industrial integration actors. According to the dynamics of the level of readiness to implement the transformation strategy, enterprises within the framework of industrial integrations are divided into three groups: enterprises with consistently high, medium, and low levels of readiness to implement the strategy.

The field cancerization theory is an important paradigm in head and neck carcinoma as its oncological repercussions affect treatment outcomes in diverse ways. The aim of this study is to assess the possible interconnection between peritumor mucosa and the process of tumor neoangiogenesis. Sixty patients with advanced laryngeal carcinoma were enrolled in this study. The majority of patients express a canonical HIF-upregulated proangiogenic signature with almost complete predominancy of HIF-1α overexpression and normal expression levels of the HIF-2α isoform. Remarkably, more than 60% of the whole cohort also exhibited an HIF-upregulated proangiogenic signature in the peritumoral benign mucosa. Additionally, the latter subgroup had a distinctly shifted phenotype towards HIF-2α upregulation compared to the one in tumor tissue, i.e., a tendency towards an HIF switch is observed in contrast to the dominated by HIF-1α tumor phenotype. ETS-1 displays stable and identical significant overexpression in both the proangiogenic phenotypes present in tumor and peritumoral mucosa. In the current study, we report for the first time the existence of an abnormal proangiogenic expression profile present in the peritumoral mucosa in advanced laryngeal carcinoma when compared to paired distant laryngeal mucosa. Moreover, we describe a specific phenotype of this proangiogenic signature that is significantly different from the one present in tumor tissue as we delineate both phenotypes, quantitively and qualitatively. This finding is cancer heterogeneity, per se, which extends beyond the “classical” borders of the malignancy, and it is proof of a strong interconnection between field cancerization and one of the classical hallmarks of cancer—the process of tumor neoangiogenesis.

Burning coal seams, characterized by massive carbon monoxide (CO) emissions, the presence of secondary sulfates, and high temperatures, represent suitable environments for thermophilic sulfate reduction. The diversity and activity of dissimilatory sulfate reducers in these environments remain unexplored. In this study, using metagenomic approaches, in situ activity measurements with a radioactive tracer, and cultivation we have shown that members of the genus Desulfofundulus are responsible for the extremely high sulfate reduction rate (SRR) in burning lignite seams in the Altai Mountains. The maximum SRR reached 564 ± 21.9 nmol S cm−3 day−1 at 60°C and was of the same order of magnitude for both thermophilic (60°C) and mesophilic (23°C) incubations. The 16S rRNA profiles and the search for dsr gene sequences in the metagenome revealed members of the genus Desulfofundulus as the main sulfate reducers. The thermophilic Desulfofundulus sp. strain Al36 isolated in pure culture, did not grow at temperatures below 50°C, but produced spores that germinated into metabolically active cells at 20 and 15°C. Vegetative cells germinating from spores produced up to 0.738 ± 0.026 mM H2S at 20°C and up to 0.629 ± 0.007 mM H2S at 15°C when CO was used as the sole electron donor. The Al36 strain maintains significant production of H2S from sulfate over a wide temperature range from 15°C to 65°C, which is important in variable temperature biotopes such as lignite burning seams. Burning coal seams producing CO are ubiquitous throughout the world, and biogenic H2S may represent an overlooked significant flux to the atmosphere. The thermophilic spore outgrowth and their metabolic activity at temperatures below the growth minimum may be important for other spore-forming bacteria of environmental, industrial and clinical importance.

Background and Aim: Anthelmintics are used to control equine nematodes. However, helminth resistance to regularly used drugs is a well-known challenge. Among tests to assess effective control and monitor resistance, the most common is the fecal egg count reduction test (FECRT). In the absence of reliable FECRT results, the nematode egg reappearance period (ERP) is taken into account. This study aimed to examine horses from farms around the Moscow Region to assess nematode resistance through ERP after therapy. Materials and Methods: In the first stage, fecal samples from 280 horses were examined by the flotation method with a sodium nitrate solution. The eggs per gram (EPG) in feces were counted using the modified McMaster technique. One hundred and forty out of 280 horses were selected for further work. Five groups were formed: Two groups of horses infected with strongyles (n = 50) and three groups with Parascaris equorum (n = 90). Therapy against strongyles was performed with albendazole and ivermectin. Therapy for parascaridosis was performed with fenbendazole, ivermectin, and aversectin C. Samples from the horses in each group were taken on the 14th day (2 weeks), 28th day (4 weeks), 42nd day (6 weeks), 56th day (8 weeks), and 84th day (12 weeks) after treatment, and the amount of EPG in each sample was determined. Results: Overall, nematodes were found in 65% of the horses examined. P. equorum was most frequently recorded (42.1%) followed by Strongylidae gen. spp. (27.9%). The strongyles ERP after therapy with albendazole and ivermectin was estimated on 42 days (6 weeks). The growth of P. equorum eggs in the feces was observed from the 56th day (8 weeks) after therapy with fenbendazole, from the 42nd day (6 weeks) after therapy with ivermectin, and was observed from the 84th day (12 weeks) after the use of aversectin. Conclusion: Our study shows widespread reductions in nematode ERPs across the Moscow Region after ivermectin therapy in horses, suggesting that additional monitoring of these farms is needed for effective control of anthelmintic resistance.

Hallucinogens like lysergic acid diethylamide (LSD), psilocybin, and substituted N-benzyl phenylalkylamines are widely used recreationally with psilocybin being considered as a therapeutic for many neuropsychiatric disorders including depression, anxiety, and substance abuse. How psychedelics mediate their actions-both therapeutic and hallucinogenic-are not understood, although activation of the 5-HT2A serotonin receptor (HTR2A) is key. To gain molecular insights into psychedelic actions, we determined the active-state structure of HTR2A bound to 25-CN-NBOH-a prototypical hallucinogen-in complex with an engineered Gαq heterotrimer by cryoelectron microscopy (cryo-EM). We also obtained the X-ray crystal structures of HTR2A complexed with the arrestin-biased ligand LSD or the inverse agonist methiothepin. Comparisons of these structures reveal determinants responsible for HTR2A-Gαq protein interactions as well as the conformational rearrangements involved in active-state transitions. Given the potential therapeutic actions of hallucinogens, these findings could accelerate the discovery of more selective drugs for the treatment of a variety of neuropsychiatric disorders.

The purpose of the article is to analyze the problems and prospects of Ukrainian-Spanish bilateral cooperation. The research is aimed at substantiating the main directions and problems, as well as the outlining of priority areas of interaction between both States. It is noted that the essence of foreign policy is that it is a mechanism that national governments use to manage diplomatic interactions and relations with other countries. It is defined that the foreign policy of the State reflects its values and goals, contributes to the achievement of its political and economic goals on the world stage. In addition, the foreign policy of some States focuses precisely on national and international security, which helps to determine how any country interacts with international organizations, such as the UN, and with citizens of other countries. The main directions of bilateral cooperation between Ukraine and Spain can be called economic and political, and recently – the military direction of cooperation. Simultaneously, the problems of bilateral cooperation between Ukraine and Spain are the violation of the economic balance between the countries, which leads to an aggravation of the crisis in the economy of both countries. Coming down to forecasting the priority directions of bilateral cooperation between Ukraine and Spain, one can assume that the main priority direction in the near future will be Spanish assistance to Ukraine in the war with the Russian Federation, post-war restoration of Ukraine, as well as assistance in integrating Ukraine into the EU and NATO. The priorities of Spain’s foreign policy are traditionally focused on Europe, the Mediterranean, North and South America. Spain strongly supports strengthening global governance, playing an active role in the multilateral system. Spain has special growing interests in the European region and cooperates with both the European Union itself, both with a like-minded actor in the region and with the EU partners, such as Ukraine. This political cooperation is supported by trade and investment ties – with a special focus on the infrastructure and renewable energy sectors.

Background. Environmental policy in the Russian Federation has been developing through the following stages: from orientation to the maximum extraction of resources towards transition to their rational use. This transition was directly related to the goals and strategic objectives of the state, as well as the economic situation in the country. Raw materials continue to play a significant role in the structure of the country’s economy, which is a decisive factor in the development of environmental policy.Aim. To analyze the environmental policy in the Russian Federation and to determine the role of natural resources in its formation and implementation.Materials and methods. The current state of environmental policy in the Russian Federation was studied in relation to the formation and development of sustainable development concepts. The legislative basis and strategic documents regulating this sphere were analyzed. The author dis­tinguishes three stages in the formation of the concept of ecological development: crisis economy, ‘ecologization’ of the society, and provision of a balance. The current stage is associated with a re­sponsible attitude to natural resources and the environment, which is accompanied by a reduction in emissions into the atmosphere, modernization of production processes, elimination of accumu­lated damage, and restoration of ecosystems. Various formats of state–society and state–business relations are considered.Results. The conducted analysis showed that the economic situation and globalization trends have a significant impact on the implementation of environmental policy. The widely spread cli­mate agenda has a mutually exclusive potential, both consolidating and divisive. The pooling of resources of several countries strengthens their positions, while the difference in the economic and technological development has a significant impact on their competitiveness.Conclusion. The Russian Federation and Russian companies will not be able to stay outside the sustainable development agenda. On the one hand, the level of technological development and the availability of natural resources have a significant impact on sustainability. On the other hand, the founders of many large domestic companies include foreign partners who are involved in global­ization processes and international agreements. Therefore, significant adjustments to the current environmental policy may be required in the near future, as a result of the revision of strategies and alliances, obligations and relationships.

Abstract Understanding the genetic targets of natural selection is one of the most challenging goals of population genetics. Some of the earliest candidate genes were identified from associations between allozyme allele frequencies and environmental variation. One such example is the clinal polymorphism in the arginine kinase (Ak) gene in the marine snail Littorina fabalis. While other enzyme loci do not show differences in allozyme frequencies among populations, the Ak alleles are near differential fixation across repeated wave exposure gradients in Europe. Here, we use this case to illustrate how a new sequencing toolbox can be employed to characterize the genomic architecture associated with historical candidate genes. We found that the Ak alleles differ by nine nonsynonymous substitutions, which perfectly explain the different migration patterns of the allozymes during electrophoresis. Moreover, by exploring the genomic context of the Ak gene, we found that the three main Ak alleles are located on different arrangements of a putative chromosomal inversion that reaches near fixation at the opposing ends of two transects covering a wave exposure gradient. This shows Ak is part of a large (3/4 of the chromosome) genomic block of differentiation, in which Ak is unlikely to be the only target of divergent selection. Nevertheless, the nonsynonymous substitutions among Ak alleles and the complete association of one allele with one inversion arrangement suggest that the Ak gene is a strong candidate to contribute to the adaptive significance of the inversion.

Abstract Microbes can play a prominent role in the evolution of their hosts, facilitating adaptation to various environments and promoting ecological divergence. The Wave and Crab ecotypes of the intertidal snail Littorina saxatilis is an evolutionary model of rapid and repeated adaptation to environmental gradients. While patterns of genomic divergence of the Littorina ecotypes along the shore gradients have been extensively studied, their microbiomes have been so far overlooked. The aim of the present study is to start filling this gap by comparing gut microbiome composition of the Wave and Crab ecotypes using metabarcoding approach. Since Littorina snails are micro‐grazers feeding on the intertidal biofilm, we also compare biofilm composition (i.e. typical snail diet) in the crab and wave habitats. In the results, we found that bacterial and eukaryotic biofilm composition varies between the typical habitats of the ecotypes. Further, the snail gut bacteriome was different from outer environments, being dominated by Gammaproteobacteria, Fusobacteria, Bacteroidia and Alphaproteobacteria. There were clear differences in the gut bacterial communities between the Crab and the Wave ecotypes as well as between the Wave ecotype snails from the low and high shores. These differences were both observed in the abundances and in the presence of different bacteria, as well as at different taxonomic level, from bacterial OTU's to families. Altogether, our first insights show that Littorina snails and their associated bacteria are a promising marine system to study co‐evolution of the microbes and their hosts, which can help us to predict the future for wild species in the face of rapidly changing marine environments.

The objective: to study specific parameters of detection of fungi of the genus Aspergillus in respiratory organs of pulmonary tuberculosis patients.Subjects and Methods. In 2019-2021, the samples of sputum or bronchoalveolar lavage of 520 patients above 18 years old with confirmed pulmonary tuberculosis and HIV-negative status were tested for molds. Also, all patients had their sputum or BAL tested for acid fast mycobacteria (AFB), cultures of M. tuberculosis (MBT), and DNA of tuberculous mycobacteria.Results. Positive culture results for fungi were obtained in 50/520 (9.62%; 95% CI 7.37-12.45, Wilson test) pulmonary tuberculosis patients. Species identification revealed fungi of the genus Aspergillus in 46/50 (92%) of them.In 37/46 (80.43%; 95% CI 66.83-89.35) patients, a single type (one species of Aspergillus) was identified, in 9/46 (19.57%; 95% CI 10.65-33.17) two types were identified. A. fumigatus (16/37 isolates, 43.24%) and A. niger (13/37 isolates, 35.14%) prevailed among single types of cultures. A. niger + A. flavus (3/9 isolates, 33.33%) was the most frequent combination. The ratio of the effectiveness of methods for detecting fungi such as culture/direct microscopy/galactomannan antigen in serum and BAL was 100/84.78/4.35% and 67.39%, respectively. Thus, BAL is more preferable than serum for detection of galactomannan antigen in patients with tuberculosis.Only in 8/46 (17.4%) patients, bacterial excretion was detected by culture, which is typical for the active phase of the course of tuberculosis. In the remaining 38 (82.6% 95% CI 69.28-90.91) patients, no tuberculous mycobacteria were detected by culture, which was typical of stabilization and cure of tuberculosis.

The objective: to develop the procedure for etiological diagnosis of infectious coxitis (IC) depending on the patient's HIV status.Subjects and Methods. The data of medical records of 97 patients with signs of IC were analyzed. Patients were divided into group depending on their HIV status.Results. The time required to diagnose IC was identified, and it made 7.35 ± 1.30 months for HIV-positive patients, and 6.25 ± 0.90 months for HIV negative patients (p > 0.05). The procedure was developed to be implemented when a patient complained of pain in the hip joint. Patients with HIV infection and suspected IC should undergo computed tomography (CT) of the hip joints, and HIV-negative patients should have CT done if the hip joint X-ray is not informative. The use of CT in the HIV+ Group reduced the diagnostic time from 9.4 ± 1.3 to 5.3 ± 1.3 months (p = 0.680), in the HIV- Group – from 8.7 ± 1.2 to 3.8 ± 0.6 months (p = 0.02). The reason why diagnosis took that long was the rare use of invasive methods at the outpatient stage. Thus, puncture of the hip joint was performed in the HIV+ Group in 2.7% of cases, in the HIV- Group – in 10%. Trepanobiopsy performed in a hospital made it possible to establish the etiology of IC in all patients. The diagnostic efficacy of microbiological tests in case of tuberculous coxitis made 48.64% in the HIV+ Group and 30.0% in the HIV- Group, in case of nonspecific coxitis it was 32.43% and 30.0%, respectively.

The article attempts to determine what makes the literary legacy of the first Russian avant-garde so special. Did Velimir Khlebnikov, Vladimir Maiakovskii, Daniil Kharms indeed pronounced a “New First Unexpected” word, as they claimed in their manifestos? On a closer look it turns out that their truly innovative feature consists not in their artistic output but rather in their self-promotion strategies resulting in power games in the field of Russian literature, in a sado-masochistic contract with the reader, and, last but not least, in the “How-to-kill-a-great predecessor” topos. Among other things, the article suggests a fresh approach to the avant-garde, which refuses to play its power games, does not accept its contract and concentrates instead on analyzing those.

Introduction: The perception of pain is subjective and many factors may affect its power and duration in various oral surgical procedures. An effective treatment suggests a certain volume of knowledge and skills of dental practitioners. A combination of non-pharmacological and pharmacological agents is often used to relieve the pain. There is evidence that non-steroidal anti-inflammatory drugs (NSAIDs) are effective in treating acute pain. Hypotheses suggest that NSAIDs have analgesic and anti-inflammatory effects by reducing the synthesis of arachidonic acid’s metabolites - prostaglandins (PGE2, PGI2), thromboxane (TxA2, TxB2) which are responsible for the occurrence of both - inflammation and pain. With the hyperalgesia initiated by PGE2 and bradykinin, we can explain the presence of postoperative pain because it reduces the pain threshold and increases susceptibility to available threshold inducements. Aim: To evaluate the effectiveness of postoperative NSAID administration in order to prevent the production of inflammatory components induced by the surgical treatment. Material and methods: The study included 15 patients who received surgical therapy. The selective COX-2 inhibitor of the new class Aulin® and the non-selective COX-2 inhibitor Ibuprofen® were taken from the patients as systemic administration postoperatively for a period of 3 days. The VRS-4 scale was used to assess the pain. Results: The assessment of the mean values for the degree of pain did not show statistically significant differences in the inhibition of pain for the two drugs in the three postsurgical days. Conclusion: In the absence of a significant difference between the two drugs - Aulin® and Ibuprofen®, we may confirm that according to our study they are both sufficiently effective in controlling postoperative pain in surgical periodontal procedures.

Relevance. In case of developed alcoholic disease, under conditions of alcoholic hypoglycemia, ketone bodies act as an energy substrate for the brain. However, the role of ketone hunger for maintaining the craving for alcohol has not been established. The assumption of such a connection has a right to exist, since it is alcohol that stimulates the formation of ketone bodies. Therefore, with developed alcoholism, the desire to consume alcohol (and, in fact, "saturate" the brain with ketone bodies) can be considered as a consequence of hypoketonemia. Accordingly, the hunger of the alcoholic is the result of hypoketonemia, but not hypoglycemia. Therefore, it is relevant to conduct a study in which the given variables (controlled by us) were the level of glycemia and the level of ketonemia, and the amount of alcohol consumed voluntarily (under conditions of free choice) was a derivative and dependent value. Objective: to study the relationship between craving for alcohol, and levels of glycemia and ketonemia in alcoholized rats. Materials and methods. Male white rats (n = 40) were forcibly alcoholized with 10% ethanol in 16 weeks. After that, for 30 days, they had a free choice of three types of drinking: clean water, 5% glucose, and 10% ethanol. The volume of consumed liquids was recorded. The criterion for the developed alcohol dependence was the preference of ethanol. At this stage, the animals were divided into 4 groups. Rats were injected per os with 0.8-1.5 ml of: 1.4% unitiol (3.5 mg / kg) to suppress ketonemia – group 1 (n = 10); 40% starch (1.0 g / kg) to eliminate hypoglycemia – group 2 (n = 10); 2.8% unitiol and 80% starch to suppress ketonemia and eliminate hypoglycemia – group 3 (n = 10); 0.9% NaCl as a control – group 4 (n = 10). Blood glucose (from the tail vein) and urine ketone bodies were monitored. The glucose level was determined with a glucometer. Test strips were used to detect ketone bodies in urine. The results were processed with MedStat software. To measure the strength of the correlation between the indicators, Spearman and Pearson tests were used. Results. No ketone bodies were found in the urine of healthy animals; however, after the end of forced alcoholization, varying levels of ketonuria were recorded in all rats: from 0.5 to 10 mmol / L (Spearman's rank correlation test was 0.8). Glycemia in healthy rats was 7.0 ± 1.4 mmol / L. After alcoholization, it decreased (p

The article is devoted to the peculiarities of digital platforms in the media business, as one of the actual possibilities of its digital transformation. The concepts of digital platform, platform business model, features of platform solutions in the media business are considered. The functional elements of the business platform are considered in detail. The main criteria for the expediency of using digital platforms are determined. The advantages and identified disadvantages of digital platforms are noted. A comparative analysis of different types of digital platforms is given. The concept and components of the media market and media business are highlighted. The publishing business has been chosen as the main object of research within the media market, since it is currently actively using the capabilities of online platforms. The current situation is considered and the prospects of using digital platforms in the media business are evaluated on the example of the publishing market. The disadvantages and limitations of the current use of business platforms in the publishing business are identified. The necessary subsystems of digital platforms in the media business for the B2B and B2C sectors are listed. A comparative analysis of existing digital platform services is presented and the main differences between the platform and the showcase are formulated. In conclusion, the need to assess the value of using the digital platform for all its participants is emphasized. The prospects of using the platform model in other segments of the media market, such as the printing market, are briefly outlined. It is revealed that the use of a platform business model within the media market will allow for more complete satisfaction of user needs, reduce transaction costs, facilitate interaction between market participants, and reduce the barrier to entry of new authors.

Purpose. The purpose of this study is to identify and further analyze the phenomenology and content-plot side of Soviet neomythology, embodying the archetype of the hero-victim in the textual materials of artistic poetry and prose for children, as well as the means used for this embodiment. Methodology. The method or methodology of doing the work. In the course of the work, the method of text analysis, content analysis, cross-factor analysis of the material of a number of sources was used according to parameters that have their own content, significant for achieving the goal stated in the study. Results. The article analyzes the structure and pragmatics of the ideologically oriented Soviet neo-myth. Particular attention was paid to the analysis of such categories as the sacralization and instrumentalization of the created mythological material, the inherent characterological features and features of the created image, which make it possible to characterize the characters created by different children’s writers as fighters, as heroes, as sacred victims. According to the results of the study, the features of the heroic character of childhood, his sacrifice and immortality, formed by the myth in the mass public perception, are identified and analyzed. In conclusion, a number of pragmatic aspects of operating the cultural image of a child-hero and a child-victim from the side of ideology, patriotic education with the help of emotions and moods of society are considered. Practical implications. The results of the study can be applied in the field of cultural studies, philosophy of culture, philosophy of literature to analyze effective and ineffective in the field of educating an active citizen and patriot through artistic techniques. The results of the analysis are acutely relevant, since modern Russian culture needs effective tools for civic and patriotic education.

Harriet Beecher Stowe's novel Uncle Tom's Cabin, or Life Among the Lowly (1852) being the most powerful statement on the racial issue in the 19th century American literature, succeeded to incorporate and rethink everything that the national tradition had in stock on the problem of slavery and race relations. The Black racial / cultural identity model that was taking shape in the 18th century Anglo-American literature, later was being enriched and transformed throughout American (and African-American) literary history. Uncle Tom's Cabin became another crucial text (the next one after Jefferson’s Notes on the State of Virginia) that provided the emerging Black cultural / racial identity model with a new quality: it became universal, nationally recognized — and at the same time a point of controversy provoking endless debates and open for dynamic change and transformations, as was the case with anti-Tom literature and the ambivalent reception of Uncle Tom’s Cabin in African American literary tradition. The analysis of The Planter’s Northern Bride (1854) by Caroline Lee Hentz, a typical example of anti-Tom novels, gives an idea of the pro-slavery response to Uncle Tom’s Cabin. The final part of the paper is a survey of the main stages in African American response since the 1853 argument between Martin Delany and Frederick Douglass that became a matrix for the further polemic, and up to Henry Louis Gates’s subversive “double-voiced” interpretation of the novel which is in full agreement with the tendency to revise the role of white Abolitionists in the antislavery movement and African American history, typical for African American studies in the 1990s–2000s.

The 20th century is the time of the birth of many scientific areas, including the physiology of the kidneys and water-salt metabolism. This article is devoted to the history of the development of one of its directions - the issue of regulation of sodium homeostasis in the body. This article is the first attempt in the Russianspeaking space to summarize the achievements in the study of sodium regulation. For many decades, scientists from different countries have studied the influence of various factors on sodium excretion: blood pressure, atrial peptides, hormones of the neurohypophysis and adrenal glands, renal nerves, infusion of various substances, etc. It was found that sodium excretion does not directly depend on changes in blood pressure and glomerular filtration rate. Atrial peptides causing natriuresis were discovered, their structure and mechanism of action were described in detail. The role of the hormones of the neurohypophysis - vasopressin and oxytocin - in the excretion of sodium, as well as the role of aldosterone and angiotensin II in the reabsorption of this cation was shown. It has been shown that the administration of hypertonic solutions of sodium chloride causes a greater natriuretic response than the administration of other substances (sodium sulfate and acetate, glucose, mannitol, etc.), and the idea of the existence of sodium-s ensitive receptors has also been put forward.

AbstractThe association between the periodontal conditions and smoking is attracting increasing attention. There is little information about the significance of the gene expression levels of interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-α) for the severity of attachment loss in patients with smoking habits. The aim of this study was to evaluate the relationship between the severity of periodontitis and the gene expression levels of IL-6 and TNF-α in the presence of a main risk factor – smoking. A total of 20 individuals (periodontitis patients) participated in this study. The following clinical parameters were studied: hygiene index, gingival bleeding index, probing depth, clinical attachment loss, furcation involvement and tooth mobility, in patients of mean age of 50.25 ± 8.45 years with untreated periodontitis. Gingival biopsies were taken adjacent to shallow ( 6 mm) periodontal pockets and similar attachment loss for Real-Time polymerase chain reaction (PCR) assessment of IL-6 and TNF-α gene expression levels. The obtained results demonstrated higher values for attachment loss and periodontal pocket depth in the presence of smoking. Furthermore, the results indicated smoking as an important risk factor which could greatly influence the studied gene expression levels. Smoking affected the gene expression mainly in conjunction with deep periodontal pockets. Our results suggest that smoking is an important risk factor for attachment loss in periodontitis patients demonstrated by clinical measurements and IL-6 and TNF-α gene expression.

Introduction. The role of disturbance of the intestinal microbiota in the development of diseases of infectious genesis and the possibility of using probiotics as an immunomodulatory agent are confirmed by the evidence base of numerous studies.Purpose. To study the results of using a multi-strain immunoprobiotic from the first days of acute respiratory infection as an emergency prevention, for the purpose of reducing the duration and severity of the disease.Materials and methods.Children from 2 to 10 years old took part in the clinical observation: the main group (45 children) received a multi-strain immunoprobiotic in accordance with the instructions for use for 1 week, starting from the 1–2 day of acute respiratory infection and the comparison group (37 children) who did not receive an immunoprobiotic.Results and discussion. As a result of the study, the effectiveness and safety of the use of an immuno-probiotic in children of preschool and primary school age, when prescribed from the first days of acute respiratory infection, and its positive effect on the course of the disease were shown. The duration of the disease in patients receiving the immunoprobiotic was statistically significantly less, and the severity of the disease was milder than in the comparison group. The incidence of repeated respiratory infections during one month after discontinuation in the main observation group was 3.1 times lower than in the comparison group. At the end of the experiment, statistically significantly higher levels of leukocytes, eosinophils, monocytes and the absolute number of lymphocytes were revealed in the comparison group that did not receive the immunoprobiotic.Conclusions. The obtained results allowed to substantiate the use of a multi-strain immuno-probiotic as a non-specific immunomodulatory agent for emergency prevention when prescribed from the first days of a respiratory infection for the purpose to reduce the duration and severity of the disease.