Research into the Degree of Impact Made by Explication of Various Ethnic Stereotypes During the Educational Process

Introduction. The article explores the impact of various types of verbal representation of ethnic stereotypes in the framework of a polyethnical academic community, i.e. educational environment in modern international university. Although the educational process with subjects of different cultural backgrounds plays a crucial role in conveying world views of representatives of different cultures, the research on the linguistic representation of stereotyped views on representatives of other nationalities has not been conducted yet. This aspect determines the relevance of the study. The aim of the research is to compare the impact levels of purely linguistic and speech ways of verbalising heterostereotypes by ways of employing relevant linguistic data for academic purposes during foreign language classes. Materials and Methods. The first stage of the experiment resulted in preparation of the linguistic corpus for the research: by means of comprehensive vocabulary research the lexical database with ethnonyms or ethnonym-based adjectives was compiled. To reveal the potential of their usage in the education processes, the participants were offered the preliminary and final surveys held as free associatio n experiment. Results. The influential potential for purely linguistic and speech ways of representing national stereotypes was compared to find out if they relate to the descriptors and scripts revealed through analysis of phraseological units and national anecdote respectively, while the latter was marked as a more efficient way of delivering ethnic stereotypes. The conclusions based on the analysis of the data obtained were drawn on how to use relevant linguistic material for academic purposes in order to appropriately develop attitudes to other ethnic groups. Discussion and Conclusions. The conducted research revealed more significant impact degree for ethnic anecdotes against investigation of lexical-phraseological units containing ethnonyms or ethnonym-based adjectives. It was illustrated by collection and further analysis of verbal reactions provided by students of non-linguistic departments of the modern University who took part in the preliminary and final stages which were in line with the beginning and end of the academic term accordingly. The portraits of typical national representatives made by the students at the completion of the course which included sessions on studying dictionary extracts and national anecdotes, to a greater extent conformed with the stereotypes delivered by ethnic anecdotes than the linguistic corpus of lexical-phraseological units. The research results may be considered during the development of the curriculum for foreign language courses in international universities with polyethnical academic environment

A New Chapter in the Treatment of Patients with Heart Failure. The Role of Sodium-Glucose Co-transporter Type 2 Inhibitors

Heart failure (HF) remains one of the major social and medical public health problems worldwide. Despite new advances in the treatment of patients with HF, the prognosis is still poor. According to the European Cardiology Society guidelines for the diagnosis and treatment of acute and chronic heart failure (CHF) 2021, a new class of drugs related to hypoglycemic has been confirmed to be effective in influencing the survival of patients with heart failure with low ejection fraction (HFpEF), regardless of the presence of disorders of carbohydrate metabolism. We are talking about inhibitors of the sodium-glucose co-transporter type 2 (iSGLT-2) or gliflozins. The article presents the results of the latest large clinical trials on the effective use of SGLT-2 in patients with HF, not only with low, but also with intact ejection fraction (HFpEF), for which there is no evidence base at the present stage. The review article presents the results of experimental studies that explored the potential mechanisms of action of gliflozins with an emphasis on new ones that are of fundamental importance for patients with heart failure, and also describes controversial and little-studied issues. Currently, there is no therapy that improves outcomes in patients with acute heart failure. The article presents the results of small analyzes of the use of iSGLT-2 in this category of patients, which are the basis for the hypothesis of their potentially effective and safe use in the case of acute decompensation of CHF, however, the role of gliflozins in this category of patients requires further in-depth study

Efficacy of iptacopan monotherapy for suboptimal response to eculizumab in patients with paroxysmal nocturnal hemoglobinuria

Aim. To evaluate the hematological response within 4 weeks of iptacopan monotherapy in patients with paroxysmal nocturnal hemoglobinuria and suboptimal response to long-term eculizumab therapy. Materials and methods. The analysis included 8 patients, median age 32 years, with persistent anemia on long-term therapy with eculizumab. The hematological response was assessed when switching to oral monotherapy with iptacopan 200 mg twice daily for 4 weeks. Results. After 4 weeks of iptacopan therapy, an increase in hemoglobin levels by more than 20 g/l was achieved in 7/8 (88%), and a complete response in 6/8 (75%) patients. The median increase in hemoglobin levels was 32.5 g/l from the initial 85.5 g/l (74–100) to 121.5 g/l (80–141); p=0.00013. Independence from red blood cell transfusions was achieved in 100% of cases. Achieving a hematological response to iptacopan therapy was accompanied by a decrease in the level of absolute reticulocyte count, bilirubin and lactate dehydrogenase, as well as a negative result of the anti-C3d direct antiglobulin test. Conclusion. The oral complement factor B inhibitor iptacopan is an effective treatment option for paroxysmal nocturnal hemoglobinuria in patients with a suboptimal response to complement inhibitor C5 due to more effective control of extravascular C3-mediated hemolysis

Clinical Efficacy and Safety of Empagliflozin in Patients with Acute Heart Failure from the First Day of Hospitalization

Aim. Evaluation of the safety, clinical and hemodynamic effects of empagliflozin in patients with acute decompensated heart failure (ADHF) from the first day of hospitalization in the absence of signs of hemodynamic instability.Material and methods. A prospective, comparative, randomized study included 46 patients admitted to the hospital in connection with ADHF in the absence of signs of hemodynamic instability. Inclusion in the study and randomization to receive empagliflozin was carried out in the first 24 hours from the moment of admission to the hospital. The main group (n=23) from the first day of hospitalization and the entire subsequent follow-up period took empagliflozin at a daily dose of 10 and 25 mg (for patients with type 2 diabetes mellitus) in addition to basic therapy, the control group (n=23) received standard therapy without gliflozines. The observation period was 3 months and included 3 control points: 1st day of hospitalization, 7th-12th day, 3rd month of observation. Clinical, anamnestic and instrumental data were evaluated at all control points.Results. In the hospital period, by the 7th-12th day, only in the main group there was an improvement in all clinical indicators (p<0.01), an increase in the rate of diuresis (p><0.01), a decrease in the daily dose of the parenteral diuretic furosemide from 54 mg to 26 mg (p><0.01). A decrease in systolic blood pressure (SBP) occurred in both groups (p><0.01), but it was more pronounced in the comparison group [from 141 (110; 160) to 110 (90; 120) mm Hg) compared to the main group [from 140 (120; 160) to 120 (110; 130) mm Hg]. According to echocardiography data in the main group, there was a decrease in the indexed volume of the right atrium, the end-systolic volume of the left ventricle (LV ESV) and systolic pressure in the pulmonary artery, an increase in the LV ejection fraction (LV EF) (p><0.05). In the comparison group, only an increase in LV ESV was noted (p=0.04). The index of the indexed volume of the left atrium did not show significant dynamics in the main group (p=0.79), but showed a significant decrease>˂0.01), a decrease in the daily dose of the parenteral diuretic furosemide from 54 mg to 26 mg (p<0.01). A decrease in systolic blood pressure (SBP) occurred in both groups (p>˂0.01), but it was more pronounced in the comparison group [from 141 (110; 160) to 110 (90; 120) mm Hg) compared to the main group [from 140 (120; 160) to 120 (110; 130) mm Hg]. According to echocardiography data in the main group, there was a decrease in the indexed volume of the right atrium, the end-systolic volume of the left ventricle (LV ESV) and systolic pressure in the pulmonary artery, an increase in the LV ejection fraction (LV EF) (p˂0.05). In the comparison group, only an increase in LV ESV was noted (p=0.04). The index of the indexed volume of the left atrium did not show significant dynamics in the main group (p=0.79), but showed a significant decrease in the 2nd and 3rd control points compared to the control group (p=0.01 and p=0.02). Complications, against the background of taking empagliflozin, were not noted: there were no episodes of hypotension (SBP˂90 mm Hg), hypoglycemia, acute kidney injury.Conclusion. The results obtained indicate the safety of empagliflozin in patients with ADHF, regardless of the status of carbohydrate metabolism and LV EF, as well as taking into account the clinical (more intense positive dynamics of clinical symptoms of ADHF) and hemodynamic (smooth decrease in SBP, increased diuretic effect) effects of empagliflozin, this drug should be considered as an effective and safe supplement to the main therapy from the first day of hospitalization in patients with stable hemodynamic parameters

The direct effect of Focal Adhesion Kinase (FAK), dominant-negative FAK, FAK-CD and FAK siRNA on gene expression and human MCF-7 breast cancer cell tumorigenesis

<p>Abstract</p> <p>Background</p> <p>Focal adhesion kinase (FAK) is a non-receptor tyrosine kinase that plays an important role in survival signaling. FAK has been shown to be overexpressed in breast cancer tumors at early stages of tumorigenesis.</p> <p>Methods</p> <p>To study the direct effect of FAK on breast tumorigenesis, we developed Tet-ON (tetracycline-inducible) system of MCF-7 breast cancer cells stably transfected with FAK or dominant-negative, C-terminal domain of FAK (FAK-CD), and also FAKsiRNA with silenced FAK MCF-7 stable cell line. Increased expression of FAK in isogenic Tet-inducible MCF-7 cells caused increased cell growth, adhesion and soft agar colony formation <it>in vitro</it>, while expression of dominant-negative FAK inhibitor caused inhibition of these cellular processes. To study the role of induced FAK and FAK-CD <it>in vivo</it>, we inoculated these Tet-inducible cells in nude mice to generate tumors in the presence or absence of doxycycline in the drinking water. FAKsiRNA-MCF-7 cells were also injected into nude mice to generate xenograft tumors.</p> <p>Results</p> <p>Induction of FAK resulted in significant increased tumorigenesis, while induced FAK-CD resulted in decreased tumorigenesis. Taq Man Low Density Array assay demonstrated specific induction of FAKmRNA in MCF-7-Tet-ON-FAK cells. DMP1, encoding cyclin D binding myb-like protein 1 was one of the genes specifically affected by Tet-inducible FAK or FAK-CD in breast xenograft tumors. In addition, silencing of FAK in MCF-7 cells with FAK siRNA caused increased cell rounding, decreased cell viability <it>in vitro </it>and inhibited tumorigenesis <it>in vivo</it>. Importantly, Affymetrix microarray gene profiling analysis using Human Genome U133A GeneChips revealed >4300 genes, known to be involved in apoptosis, cell cycle, and adhesion that were significantly down- or up-regulated (p < 0.05) by FAKsiRNA.</p> <p>Conclusion</p> <p>Thus, these data for the first time demonstrate the direct effect of FAK expression and function on MCF-7 breast cancer tumorigenesis <it>in vivo </it>and reveal specific expression of genes affected by silencing of FAK.</p

Overcoming Multidrug Resistance via Photodestruction of ABCG2-Rich Extracellular Vesicles Sequestering Photosensitive Chemotherapeutics

Multidrug resistance (MDR) remains a dominant impediment to curative cancer chemotherapy. Efflux transporters of the ATP-binding cassette (ABC) superfamily including ABCG2, ABCB1 and ABCC1 mediate MDR to multiple structurally and functionally distinct antitumor agents. Recently we identified a novel mechanism of MDR in which ABCG2-rich extracellular vesicles (EVs) form in between attached neighbor breast cancer cells and highly concentrate various chemotherapeutics in an ABCG2-dependent manner, thereby sequestering them away from their intracellular targets. Hence, development of novel strategies to overcome MDR modalities is a major goal of cancer research. Towards this end, we here developed a novel approach to selectively target and kill MDR cancer cells. We show that illumination of EVs that accumulated photosensitive cytotoxic drugs including imidazoacridinones (IAs) and topotecan resulted in intravesicular formation of reactive oxygen species (ROS) and severe damage to the EVs membrane that is shared by EVs-forming cells, thereby leading to tumor cell lysis and the overcoming of MDR. Furthermore, consistent with the weak base nature of IAs, MDR cells that are devoid of EVs but contained an increased number of lysosomes, highly accumulated IAs in lysosomes and upon photosensitization were efficiently killed via ROS-dependent lysosomal rupture. Combining targeted lysis of IAs-loaded EVs and lysosomes elicited a synergistic cytotoxic effect resulting in MDR reversal. In contrast, topotecan, a bona fide transport substrate of ABCG2, accumulated exclusively in EVs of MDR cells but was neither detected in lysosomes of normal breast epithelial cells nor in non-MDR breast cancer cells. This exclusive accumulation in EVs enhanced the selectivity of the cytotoxic effect exerted by photodynamic therapy to MDR cells without harming normal cells. Moreover, lysosomal alkalinization with bafilomycin A1 abrogated lysosomal accumulation of IAs, consequently preventing lysosomal photodestruction of normal breast epithelial cells. Thus, MDR modalities including ABCG2-dependent drug sequestration within EVs can be rationally converted to a pharmacologically lethal Trojan horse to selectively eradicate MDR cancer cells

10-year experience in orthotopic heart transplantation in Kuzbass

Background. Orthotopic heart transplantation (OHT) is the gold standard treatment for individuals with endstage heart failure (HF), providing the best survival and quality of life. In Russia, the number of OHT procedures and transplantation of other organs have significantly increased in recent years. At the same time, there is lower perioperative mortality and higher survival in the post-OHT long-period.Objective: to analyze OHT outcomes in Kuzbass over a 10-year period.Material and methods. From January 2013 to December 2023, 72 OHTs (36.7% of those included on the heart transplant waiting list (HTWL) over a 10-year period) were performed at the Research Institute for Complex Issues of Cardiovascular Diseases. Recipient median age was 56 [50.5; 61.0] years, which included 61 men and 11 women. Among the etiologic causes of end-stage HF, ischemic cardiomyopathy was predominant in 65.3% (n = 47) of recipients, whereas dilated cardiomyopathy was present in 25% (n = 18) of recipients. Other cardiomyopathies accounted for 9.7% (n = 7).Results. A total of 196 patients with end-stage HF were included in the HTWL over a 10-year period; 74 (37.8%) of these did not live to get a transplant. The waitlist time was 173 days (5.77 months) – which is slightly longer than the average waiting time of 3.9 months for OHT according to data from European registries. Waitlist mortality was 19.6%. The 10-year average in-hospital mortality rates among patients after OHT were 16.7% and 1-year mortality was 15.3%. These rates are consistent with worldwide trends for this high-tech medical care. Cumulative survival at the end of 2023 was 51.4% (36 patients after OHT). Median length of stay in the hospital was 28 days, with 14 days spent in the intensive care unit. Donor heart anoxia time was 112 [85.25; 170.5] minutes, and cardiopulmonary bypass time was 145 [124; 169.5] minutes. Ten patients (13.9%) required extracorporeal membrane oxygenation, while 8.3% of cases required extracorporeal homeostasis correction.Conclusion. The 10 years of successful experience at the Research Institute for Complex Issues of Cardiovascular Diseases validates the need to develop the OHT program in Kuzbass as a gold standard for treating end-stage HF

COVID-19 at War: The Joint Forces Operation in Ukraine

The ongoing pandemic disaster of coronavirus erupted with the first confirmed cases in Wuhan, China, in December 2019, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) novel coronavirus, the disease referred to as coronavirus disease 2019, or COVID-19. The World Health Organization (WHO) confirmed the outbreak and determined it a global pandemic. The current pandemic has infected nearly 300 million people and killed over 3 million. The current COVID-19 pandemic is smashing every public health barrier, guardrail, and safety measure in underdeveloped and the most developed countries alike, with peaks and troughs across time. Greatly impacted are those regions experiencing conflict and war. Morbidity and mortality increase logarithmically for those communities at risk and that lack the ability to promote basic preventative measures. States around the globe struggle to unify responses, make gains on preparedness levels, identify and symptomatically treat positive cases, and labs across the globe frantically rollout various vaccines and effective surveillance and therapeutic mechanisms. The incidence and prevalence of COVID-19 may continue to increase globally as no unified disaster response is manifested and disinformation spreads. During this failure in response, virus variants are erupting at a dizzying pace. Ungoverned spaces where nonstate actors predominate and active war zones may become the next epicenter for COVID-19 fatality rates. As the incidence rates continue to rise, hospitals in North America and Europe exceed surge capacity, and immunity post infection struggles to be adequately described. The global threat in previously high-quality, robust infrastructure health-care systems in the most developed economies are failing the challenge posed by COVID-19; how will less-developed economies and those healthcare infrastructures that are destroyed by war and conflict fare until adequate vaccine penetrance in these communities or adequate treatment are established? Ukraine and other states in the Black Sea Region are under threat and are exposed to armed Russian aggression against territorial sovereignty daily. Ukraine, where Russia has been waging war since 2014, faces this specific dual threat: disaster response to violence and a deadly infectious disease. To best serve biosurveillance, aid in pandemic disaster response, and bolster health security in Europe, across the North Atlantic Treaty Alliance (NATO) and Black Sea regions, increased NATO integration, across Ukraine’s disaster response structures within the Ministries of Health, Defense, and Interior must be reinforced and expanded to mitigate the COVID-19 disaster

Copper Deficiency Induced Emphysema Is Associated with Focal Adhesion Kinase Inactivation

Background: Copper is an important regulator of hypoxia inducible factor 1 alpha (HIF-1a) dependent vascular endothelial growth factor (VEGF) expression, and is also required for the activity of lysyl oxidase (LOX) to effect matrix protein crosslinking. Cell detachment from the extracellular matrix can induce apoptosis (anoikis) via inactivation of focal adhesion kinase (FAK). Methodology: To examine the molecular mechanisms whereby copper depletion causes the destruction of the normal alveolar architecture via anoikis, Male Sprague-Dawley rats were fed a copper deficient diet for 6 weeks while being treated with the copper chelator, tetrathiomolybdate. Other groups of rats were treated with the inhibitor of auto-phosphorylation of FAK, 1,2,4,5-benzenetetraamine tetrahydrochloride (1,2,4,5-BT) or FAK small interfering RNA (siRNA). Principal Findings: Copper depletion caused emphysematous changes, decreased HIF-1a activity, and downregulated VEGF expression in the rat lungs. Cleaved caspase-3, caspase-8 and Bcl-2 interacting mediator of cell death (Bim) expression was increased, and the phosphorylation of FAK was decreased in copper depleted rat lungs. Administration of 1,2,4,5-BT and FAK siRNA caused emphysematous lung destruction associated with increased expression of cleaved capase-3, caspase-8 and Bim. Conclusions: These data indicate that copper-dependent mechanisms contribute to the pathogenesis of emphysema