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Magnesium alloys are considered promising materials for the production of bioresorbable implants. Their main disadvantages are low strength and corrosion resistance in biological environment. In the work, the authors studied the effect of severe plastic deformation using the equal channel angular pressing (ECAP) method on the structure, mechanical properties, and corrosion resistance of the Mg–8.6Zn–1.2Zr magnesium alloy. It was identified that one ECAP cycle at 400 °C leads to a substantial hardening of the Mg–8.6Zn–1.2Zr alloy by ~10 %, up to 330 MPa. Structural studies showed that dynamic recrystallisation plays a significant role in the structure transformation. ECAP leads to the formation of a bimodal structure with large deformed grains with an average transverse size of 20±4 µm and recrystallised grains with an average transverse size of 6±2 µm. It was found that with a decrease in the strain temperature up to 250 °С, the process of deformation-induced decay of the supersaturated solid solution takes place. Electrical conductivity of a sample after ECAP at 400 °C amounted 29±2 % according to the International Annealed Copper Standard (IACS), while second ECAP cycles lead to an increase in the electrical conductivity up to 32±2 % IACS. Using the electrochemical corrosion method, the authors found that one ECAP cycle at 400 °C leads to a slight decrease in the corrosion resistance of the alloy under study compared to the initial state. The study showed that the corrosion current increases from 24 to 32 µA/cm2, while the subsequent ECAP cycle at 250 °С increases the corrosion current more than twice (up to 57 µA/cm2).

Introduction: The effectiveness of ulcerative colitis (UC) treatment is fairy moderate and it gives a rise to search for new ways of treating it. Considering the combination of dalargin effects, studying the dalargin influence on the UC development is of undoubted interest. The aim of the study was to evaluate the dalargin effect on the content of transforming growth factor-β (TGF-β) and epidermal growth factor (EGF) in the colonic wall in mice with experimental ulcerative colitis. Materials and methods: UC was simulated by replacing water with a 5% solution of dextran sodium sulfate in boiled water for 5 days. The mice were killed on the 5th, 7th and 28th days. The concentrations of TGF-β and EGF in the homogenate of the medial colon were determined by enzyme-linked immunosorbent assay using standard kits. Results and discussion: The dalargin daily subcutaneous administration (dose of 100 μg/kg) for 7 days led to a decrease in TGF-β levels on the 5th and 7th days compared to the control group. In chronic UC, the concentration of TGF-β was higher than in the control group. The EGF concentration was increased in mice with UC treated with dalargin throughout the experiment. There were no differences in dalargin and sulfasalazine effects on the content of TGF-β, and the concentration of EGF throughout the experiment was significantly higher in the animals treated with dalargin. Conclusion: Effect of dalargin on the TGF-β and EGF concentrations was explained by its stimulating action to opioid μ-receptors localized on immune cells of the colon.

Introduction. The trend of large-scale work by authorities on the delimitation of state property; the introduction into circulation of agricultural land plots for the development of the agro-industrial complex and land plots in settlements to stabilize the construction complex; registration of rights to extortionate property and ownerless immovable things – with the transfer of all these objects to municipal ownership, caused the need to improve both the legal regulation system and management tools. From the point of view of law, there is a need to clarify the signs of ownerless maintenance of real estate, on the part of management – the introduction of criteria for assessing the suitability of an ownerless object as municipal property. The purpose of the study is to develop an economic and legal approach to regulating the process of transferring ownerless real estate to municipal ownership and determining the prospects for its use. Materials and methods. Current laws and regulatory legal acts; statistical and analytical information from the Federal Register of the Russian Federation, the Supreme Court of the Russian Federation; open data from municipalities. The research is based on an interdisciplinary approach: legal analysis, content analysis, classification; the concept of management decisions, the economic location of the property, methods of real estate valuation. The results of the study are to clarify the signs of ownerless real estate, to detail the process of changing the status of real estate from ownerless to municipal with a description of the nuances of each stage, to develop a model for making managerial decisions to determine the prospects for the use of municipal real estate. Discussion. The economic and legal approach to regulating the transition of ownerless real estate to the status of municipal property consists in the economic justification of the value and usefulness of real estate for a municipality during its procedural registration from an ownerless state. Each proposed innovation will be possible to use in practice after the adoption of local regulations and administrative regulations. The results obtained can be used to further improve the legal and economic mechanisms for improving the efficiency of municipal property management.

Lipid peroxidation is a major process that determines the quality of various oil samples during their use and storage, in which the primary products are hydroperoxides (HP’S). HP’S are very stable compounds at ambient conditions and are harmful to human health. Therefore, the evaluation of the degree of oil oxidation is an excellent tool for ensuring food safety. The peroxide value (PV) is the main parameter used for quality control in oils. Herein, we propose an alternative electrochemical method to the classical iodometric titration method most widely used for determining the PV. Our approach is based on the electrochemical quantification of hydroperoxides/peroxides in an organic solvent medium (acetonitrile and organic ammonium salt) using a composite electrocatalyst–glassy carbon electrode modified with 2D-nanomaterial graphitic carbon nitride doped with Co3O4. Calibration was made by the method of standard addition using benzoyl peroxide (BPO) as a model peroxide compound, dissolved in chloroform and added to fresh Rivana-branded anti-cellulite oil, used as a model oil sample. Calibration plots showed a linear response and the very good reproducibility of the analytical result (R2 ˃ 0.99). Further, in terms of accuracy, the method showed good results, since the BPO quantitative analysis was close to the theoretical response. In addition, the accuracy of the electrochemical method was compared with that of the standard iodometric titration method for determining the PV of vegetable fats (according to a standard method). Finally, using the electrochemical method, the concentration of peroxides was determined in a real sample—an anti-cellulite oil of the trademark Rivana with an expired shelf life.

Background: Although mRNA vaccines encapsulated in lipid nanoparticles (LNPs) have demonstrated a safety profile with minimal serious adverse events in clinical trials, there is opportunity to further reduce mRNA reactogenicity. The development of naked mRNA vaccines could improve vaccine tolerability. Naked nucleic acid delivery using the jet injection method may be a solution. Methods: In the first part of the study, the optimal conditions providing low traumatization and high expression of the model mRNA-GFP molecule in the tissues of laboratory animals were determined. Then, we used the selected protocol to immunize BALB/c mice with mRNA-RBD encoding the SARS-CoV-2 receptor-binding domain (RBD). It was demonstrated that mice vaccinated with naked mRNA-RBD developed a high level of specific antibodies with virus-neutralizing activity. The vaccine also induced a strong RBD-specific T-cell response and reduced the viral load in the lungs of the animals after infection with the SARS-CoV-2 virus. The level of immune response in mice immunized with mRNA-RBD using a spring-loaded jet injector was comparable to that in animals immunized with mRNA-RBD encapsulated in LNPs. Results: In this study, the efficacy of an inexpensive, simple, and safe method of mRNA delivery using a spring-loaded jet injector was evaluated and validated. Conclusions: Our findings suggest that the jet injection method may be a possible alternative to LNPs for delivering mRNA vaccines against SARS-CoV-2 infection.

Reactive oxygen species (ROS) within the retina play a key role in maintaining function and cell survival. However, excessive ROS can lead to oxidative stress, inducing dysregulation of metabolic and inflammatory pathways. The chmru848 zebrafish models choroideremia (CHM), an X-linked chorioretinal dystrophy, which predominantly affects the photoreceptors, retinal pigment epithelium (RPE), and choroid. In this study, we examined the transcriptomic signature of the chmru848 zebrafish retina to reveal the upregulation of cytokine pathways and glia migration, upregulation of oxidative, ER stress and apoptosis markers, and the dysregulation of glucose metabolism with the downregulation of glycolysis and the upregulation of the oxidative phase of the pentose phosphate pathway. Glucose uptake was impaired in the chmru848 retina using the 2-NBDG glucose uptake assay. Following the overexpression of human PFKM, partial rescue was seen with the preservation of photoreceptors and RPE and increased glucose uptake, but without modifying glycolysis and oxidative stress markers. Therapies targeting glucose metabolism in CHM may represent a potential remedial approach.

The rise in electricity costs for households over the past year has driven significant changes in energy usage patterns, with many residents adopting smarter energy-efficient practices, such as improved indoor insulation and advanced home energy management systems powered by IoT and Digital Twin technologies. These measures not only mitigate rising bills but also ensure optimized thermal comfort and sustainability in typical residential settings. This paper proposes an innovative framework to facilitate the adoption of energy-efficient practices in households by leveraging the integration of Internet of Things technologies with Digital Twins. It introduces a novel approach that exploits standardized parametric 3D models, enabling the efficient simulation and optimization of home energy systems. This design significantly reduces deployment complexity, enhances scalability, and empowers users with real-time insights into energy consumption, indoor conditions, and actionable strategies for sustainable energy management. The results showcase that the proposed method significantly outperforms traditional approaches, achieving a 94% reduction in deployment time and a 98% decrease in memory usage through the use of standardized parametric models and plug-and-play IoT integration.

Background/Objectives: Wilson’s disease (WD) (OMIM 277900) or hepatolenticular degeneration is an autosomal recessive disorder caused by impaired copper excretion with subsequent accumulation in the liver, brain, and other tissues of the body. The defects in copper metabolism are based on various pathogenic variants of the ATP7B gene encoding copper-transporting P-type ATPase. The aim of this work is to search for pathogenic variants of the ATP7B gene among Eastern Eurasian patient cohorts and to pick correlations between pathogenic variants, gender, age of onset of the disease, and the course of the disease. Methods: The material for the study was the biomaterial of 100 people. The search for mutations was carried out by Sanger sequencing. Multiple alignment of nucleotide sequences and their analysis was performed using the MEGA-X software. To study the genotype-phenotypic correlation, an analysis of the medical records of each patient was carried out. Results: Most common pathogenic variant (48%) in the sample is p.His1069Gln (c.3207C>A), located in exon 14 of the ATP7B gene. Pathogenic variants of p.Glu1064Lys (c.3190G>A)—20%—and p.Met769HisfsTer26 (c.2304insC)—8%—of exons 14 and 8 were also common. For patients with pathogenic alleles p.His1069Gln (c.3207C>A) and p.Glu1064Lys (c.3190G>A), typical deviations are mental and neurological manifestations of WD. In patients with the pathogenic allele p.Met769HisfsTer26 (c.2304insC), deviations are more characteristic of the liver and a combination of various symptoms that are atypical for WD. Conclusions: In this study, we were able to obtain differences in symptoms in patients with different pathogenic alleles of the ATP7B gene.

Malignant pleural mesothelioma is a neoplasm that is often detected late due to nonspecific symptoms. This study utilized NSG-SGM3 mice to examine interactions between a human-derived mesothelioma reporter cell line (MZT-Luc2-mCherry) and the host’s myeloid compartment. Tumor growth was assessed using optical tomography, while cytokine/chemokine production was analyzed via multiplex assay. Histological and immunohistochemical analyses validated the epithelioid mesothelioma phenotype. In vitro mesothelioma cells secreted factors associated with myeloid cell chemoattraction and functions supporting the previously reported myeloid-biased secretory phenotype. In line with this, post-engraftment analysis revealed increased neutrophil-like Ly6G+ populations and decreased Ly6C+ inflammatory monocytes in the blood of tumor-bearing mice. Significant Ly6G+ cell infiltration was observed in the tumor, while CD11b+ myeloid cells were localized primarily in the tumor periphery. Tumor lysates showed increased levels of neutrophil chemoattractants and G-CSF, suggesting a previously not reported role of neutrophils in mesothelioma progression. This novel model provides a platform for studying mesothelioma–host interactions, focusing on the myeloid compartment. It may also serve as a tool to facilitate the development of new therapeutic strategies targeting myeloid cell-mediated mechanisms in mesothelioma.

Background: Rhabdomyosarcoma (RMS) is a highly malignant soft tissue tumor derived from primitive embryonal mesenchymal tissue that differentiates into striated skeletal muscle. Despite the improved outcome based on the EFS and OS using the three different treatment modalities-chemotherapy, radiotherapy and surgical treatment, the survival of patients depends on their IRS groups—pathological and surgical. On the other hand in the last thirty years a great improvement of the five-year overall survival (OS) of children with RMS have been observed based on the results of large multinational collaborative trials and successive studies dedicated to children, though prognosis is variable and dependent on several factors including histologic variant, primary sites of the tumor, extent of disease (disease resectability), and molecular-level characteristics. Case presentation: We present a clinical case of a five-year-old male with initial complains of left side peripheral facial nerve palsy and secondary cervical and retroauricular lymphadenomegaly. After an exam, surgery of the temporal bone, CT and MRI embryonal type of rhabdomyosarcoma was diagnosed, and adjuvant chemotherapy was initiated in combination with concomitant local radiotherapy. Results: The results show that in these areas surgery itself is insufficient for RMS treatment(usually it is limited to taking a biopsy only). The combination of chemotherapy and local control with radiotherapy achieved a good result in our patient. Conclusions: Middle ear Embryonal Rhabdomyosarcoma is a common solid tumor, which could mimic middle ear inflammation or mastoid inflammation in patients. The multimodal approach seemed to be the ideal management of RMS. It involves a combination of chemotherapy and local control with surgery and/or radiotherapy.

The local application of broad-spectrum antibiotics via polymeric drug delivery systems is a promising alternative to their systemic administration in wound healing, prevention and treatment of infections associated with surgical implants. However, low and poorly controlled loading efficiency and 100% burst release are common problems for the materials with weak physical interaction between antibiotics and polymeric matrices. Here, we report a new multifunctional carboxymethyl chitosan (CMC) cryogel, which efficiently prevents bacterial adhesion to the surface, kills bacteria in the solution via controlled release of ciprofloxacin (CIP), and promotes fibroblast proliferation. The suggested approach is based on CIP loading to Zn2+-chelated CMC cryogel via the ligand exchange reaction. We have shown that, due to the strong binding of Zn2+ to CMC, the antibacterial effect and toxicity to fibroblasts of CMC-Zn-CIP cryogels were mainly determined by the content of loaded CIP, which can be precisely controlled via Zn2+ content in cryogel. CMC cryogels containing 20 mgZn/g can be loaded with CIP amounts sufficient to completely suppress the growth of hospital strain Klebsiella oxytoca with MIC of 0.125 µg/mL, while maintaining a fibroblast viability at the level of 85–90%.

Situs anomalies, including situs inversus and situs ambiguous (SAMB), are rare congenital conditions typically noted in pediatric populations, with SAMB being particularly uncommon in adults. This case study addresses the incidental discovery of situs ambiguous with polysplenia in a 65-year-old man evaluated for suspected adrenal adenoma. The patient’s medical history included benign prostatic hyperplasia and tuberculous pleurisy. Methods included a thorough physical examination and laboratory tests, which showed normal cortisol levels and ACTH rhythm. Contrast-enhanced CT imaging revealed multiple spleens near the right adrenal region, altered liver positioning, a truncated pancreas, and a right-sided stomach, while the right adrenal gland was not visualized. Notably, the patient exhibited minimal symptoms despite these significant anatomical anomalies. The findings underscore the rarity of situs ambiguous in adults and its unexpected association with endocrine pathology. This case highlights the importance of comprehensive imaging and a multidisciplinary approach in managing patients with unusual anatomical presentations. It suggests that situs anomalies may be more prevalent in adult populations than previously recognized and emphasizes the need for increased clinical awareness and evaluation in similar cases.

Rhinoviruses and respiratory enteroviruses remain among the leading causes of acute respiratory infections, particularly in children. Little is known about the genetic diversity of enteroviruses and rhinoviruses in pediatric patients with acute respiratory infections in Russia. We assessed the prevalence of human rhinoviruses/enteroviruses (HRV/EV) in 1992 children aged 0 to 17 years hospitalized with acute respiratory infections during the 2023–2024 epidemic season using PCR. The detection rate of HRV/EV was 11% (220/1992). We performed typing of 58 HRV and 28 EV viruses by partial sequencing of the VP1 gene. Rhinovirus A was the most common among HRV, followed by rhinovirus C; rhinovirus B was detected in only three cases. Enteroviruses were represented by all four species, with the EV-D68 genotype being the most frequently detected. Phylogenetic analysis of the VP1 fragment of EV-D68 showed that all our sequences belonged to the B3 subclade. We identified the first case of EV-C105 infection in Russia in a two-year-old girl hospitalized with pneumonia. Phylogenetically, the Novosibirsk strain EV-C105 was closely related to a strain discovered in France in 2018. This research helped to fill a critical gap in understanding the epidemiological landscape of HRV/EV in pediatric populations within Russia.

A challenge to contemporary medicine is still the discovery of an effective and safe therapy for symptomatic control, if not cure, of Parkinson’s disease. While the potential century’s break-through is sought and foreseen by many scientists in gene therapy, immunotherapy, new drug combinations, and neurosurgical approaches, the not-yet-conventional intranasal administration of “classic” levodopa (L-DOPA) also stands out as a perspective from which Parkinson’s patients may benefit in the short term. With the main drawbacks of the standard oral L-DOPA treatment being the extremely low systemic and cerebral bioavailability, it is widely recognized that the nasal route may turn out to be the better administration site, for it offers the alternative of direct brain delivery via the olfactory bulb (the so-called nose-to-brain axis). However, such advancement would be unthinkable without the current progress in nano-scaled drug carriers which are needed to ensure drug stability, mucosal retention and permeation, olfactory uptake, and harmlessness to the sensory neurons and respiratory cilia. This study aims to review the most significant results and achievements in the field of nano-particulate nose-to-brain delivery of L-DOPA.

ABSTRACT: Objectives: Antiretroviral (ARV) drugs have played a vital role in controlling the HIV-1 epidemic; however, some challenges remain. ARV drugs vary in their ability to control HIV infection, displaying differences in treatment-limiting factors and genetic barriers to resistance. The current report assesses the prevalence of HIV-1 drug resistance mutations (DRMs) among patients who failed first-line antiretroviral therapy (ART) and evaluates the genetic barrier of different regimens. Methods: The study cohort (n = 271) included HIV-infected individuals who visited the Novosibirsk, Russia, HIV/AIDS clinic in 2018–2022. All patients received first-line ART prior to virological failure. Sociodemographic and HIV-related data were collected from medical records and self-reported questionnaires. HIV-1 pol gene sequences were generated, and the presence of HIV-1 DRM was assessed. The genetic barrier to resistance was assessed by combining treatment regimen and adherence data. Results: Nonoptimal ART adherence was identified in 48.3% of patients and correlated with male sex, PWID, unemployment, and rural area residence. Most of the patients with high-level adherence were identified among those who were on TDF+3TC+DTG. HIV-1 DRMs were identified in 54.6% of the patients. The analysis of HIV-1 DRM, ART regimen, and adherence data classified TDF+3TC+DTG and TDF+3TC+LPV/r as treatment regimens with a high genetic barrier, whereas EFV-containing ART was classified as a regimen with a low genetic barrier. Conclusions: The current study delivers results on the efficacy of HIV-1 ART and treatment adherence in real-world practice settings. This report suggests that ART regimens with a high genetic barrier to resistance combined with improved treatment adherence may reduce the transmission of HIV-1 resistant variants.

The relevance of the research is determined by the insufficient study of the forms of aggression in the context of culture, as well as insufficient description of the extralinguistic prerequisites of aggression correlated with the subject area of culture, and intra-linguistic means and methods of cultural reference of aggression. The aim of the study is to identify the linguistic and cultural foundations of expressing aggression in the Russian language and to describe the means of its verbalization through the prism of the binary category “Own/ Other”, which is the basis of ethnic conflicts. To achieve this aim, the method of definitional, semantic, linguistic-cultural analysis, descriptive method was used. A sociolinguistic experiment was conducted. Methods of continuous sampling from lexicographic sources and of quantitative calculations of the responses received by the participants of the experiment were applied. The research material included: 1) a corpus of more than 50 lexical and phraseological units of the Russian language taken from dictionaries, which verbalize aggressive attitude towards “foreign” culture and “foreign” ethnos; 2) a range of ethnopholisms obtained in the sociolinguistic experiment among high school students in Astrakhan. It was determined that aggression in the Russian language has a culturological explanation: it is conditioned by identifying the ethnos according to the principle of “own - other”. The linguistic and cultural basis of aggressive semantics is the semantics of “alienness”, which is expressed by demonstrating an obviously negative attitude to “alien”, which is the object of an aggressive action. A special group of lexical means - linguistic and cultural markers of aggression - includes units, negatively characterizing representatives/artifacts of a “foreign” culture. Linguistic and cultural markers of aggression are ethnopholisms. Aggressive nominations of ethnic groups historically residing both far abroad and in the Russian multicultural region are equally relevant in the linguistic consciousness of young people. From extralinguistic positions, the consolidation and activation of hostile lexico-phraseological means in the language are conditioned by the intercultural historical contacts of nations which are currently being reflected in the journalistic discourse, in Internet communication. The perspective of the research is seen in the use of its results for developing the concept of overcoming speech aggression in the educational space, where the factor of hostility has hindered the education of a tolerant personality.

Summary: Bacteria dysbiosis and its accompanying inflammation or compromised mucosal integrity is associated with an increased risk of HIV-1 transmission. However, HIV-1 may also bind bacteria or bacterial products to impact infectivity and transmissibility. This study evaluated HIV-1 interactions with bacteria through glycan-binding lectins. The Streptococcal Siglec-like lectin SLBR-N, a part of the fimbriae shrouding the bacteria surface that recognizes α2,3 sialyated O-linked glycans, was noted for its ability to enhance HIV-1 infectivity in the context of cell-free infection and cell-to-cell transfer. Enhancing effects were recapitulated with O-glycan-binding plant lectins, signifying the importance of O-glycans. N-glycan-binding bacterial lectins FimH and Msl had no effect. SLBR-N was demonstrated to capture and transfer infectious HIV-1 virions, bind to O-glycans on HIV-1 Env, and increase HIV-1 resistance to neutralizing antibodies targeting different regions of Env. This study highlights the potential contribution of O-glycan-binding lectins from commensal bacteria at the mucosa in promoting HIV-1 infection.

Although their exceptional re-passivation ability, Al-alloys are susceptible to corrosion due to the amphoteric nature of the alumina passivation films. This issue is exacerbated by the disruption of these films by intermetallics on the surfaces of highly doped ones, like AA2024-T3 aircraft alloy. The combination of anodized aluminium oxide (AAO) and cerium conversion coatings (CeCC) shows promise as a coating primer. However, the defective structures of CeO2 and Al2O3 require additional sealing. This research proposes sealing the CeCC/AAO layer by boiling it for 10 minutes in two relatively neutral Lourier buffers, adjusted to pH 7.75, and in a mixture of them. The samples underwent a series of analyses to compare the impact of the sealing procedure on surface topology, properties (e.g., colour and wettability on two samples from each set), and corrosion protective ability. It was assessed after 24 hours of exposure to 3.5 % NaCl model corrosive medium on six samples from each set. The assessments included electrochemical impedance spectroscopy (EIS) and potentiodynamic scanning (PDS) techniques. The results indicate that the borate buffer improves the corrosion protection of the coating primers more effectively than the phosphate and mixed ones.

Aging is associated with an increased risk of developing pain, especially in the presence of concurrent chronic clinical conditions. Similarly, multimorbidity can affect the perception and ability of older adults to appropriately respond to and communicate pain, and there is a clinical heterogeneity in the processing of painful sensations in different neurological conditions. The present narrative review is aimed at assessing the prevalent diseases associated with poor communication and pain in older adults, together with the available diagnostic instruments for the clinical assessment of pain in such a vulnerable population. Dementia was the most described pathology identified in the current literature associated with poor communication in older adults affected by pain, along with Parkinson’s disease and stroke. Notably, a common pattern of pain behaviors in these neurological disorders also emerged, indicating potential similarities in the clinical presentation and appropriate diagnostic workout. At the same time, there are many differences in the way patients express their pain according to their main neurological pathology. In addition to this, although a plethora of observation-based tools for pain in patients with dementia have been developed, there is no gold standard, and the clinical utility of such measurements is still largely unaddressed. Meanwhile, there is substantially no standardized observation-based tool for pain in non-communicative patients with Parkinson’s disease, and only a few for stroke. Overall, the present narrative review provides an update on the prevalent diseases beyond dementia associated with a communicative disability and a painful condition in older adults.

The paper aims to investigate the causal nexus of the parameters of financial and economic security and the development of priority sectors of the national economy (on the example of agriculture, industry, construction, and transport in Ukraine) in the years 2010-2021. The results of the causal analysis showed the greatest degree of variability in the development of Ukrainian industry from the production, economic, credit and debt components of its financial security; agriculture, forestry, and fisheries – the security of money circulation and the credit component of financial security; construction, transport, warehousing, postal and courier – all components of financial security, except investment. The practical significance of the research results lies in the development of tools for modelling the impact of policy measures of strengthening financial and economic security on the development of priority sectors of the national economy, which allows for predicting the consequences of the implementation of the state security policy in the field of structural and institutional changes.

Summary: Human genetic studies of critical COVID-19 pneumonia have revealed the essential role of type I interferon-dependent innate immunity to SARS-CoV-2 infection. Conversely, an association between the HLA-B∗15:01 allele and asymptomatic SARS-CoV-2 infection in unvaccinated individuals was recently reported, suggesting a contribution of pre-existing T cell-dependent adaptive immunity. We report a lack of association of classical HLA alleles, including HLA-B∗15:01, with pre-omicron asymptomatic SARS-CoV-2 infection in unvaccinated participants in a prospective population-based study in the United States (191 asymptomatic vs. 945 symptomatic COVID-19 cases). Moreover, we found no such association in the international COVID Human Genetic Effort cohort (206 asymptomatic vs. 574 mild or moderate COVID-19 cases and 1,625 severe or critical COVID-19 cases). Finally, in the Human Challenge Characterisation study, the three HLA-B∗15:01 individuals infected with SARS-CoV-2 developed symptoms. As with other acute primary infections studied, no classical HLA alleles favoring an asymptomatic course of SARS-CoV-2 infection were identified.

Introduction: Traps at the interface between carbyne and palladium nanocoatings, produced at different growth conditions, are explored by current-voltage characteristics, scanning electron microscopy and thermal stimulation of charges for evaluation of their nature. It was found that the Pd films can form an Ohmic contact with the carbyne at certain deposition conditions and such deviated from the Ohmic behavior according to the RF sputtering voltage. This growth parameter was found to affect the interfacial traps formation on the carbyne surface, which is important feature for the charge trapping and releasing properties for hydrogen isotopes in the context of the energy release applications.Methods, Results and Discussion: The sputtering voltages of 0.5 kV and 0.7 kV were found unsuitable for controlled trap formation. Based on the currentvoltage and thermally stimulated current (TSC) measurements, a sputtering voltage of 0.9 kV appeared to be more favorable compared to 0.5 kV and 0.7 kV. At 0.9 kV thermal activation of charge carriers are enabled at lower thermal energies, showing a distinct change in TSC behavior correlated to trap activation.

BackgroundBreast cancer (BC) mortality primarily stems from metastases rather than the primary tumor itself. Perioperative stress, encompassing both surgical and anesthetic factors, profoundly impacts the immune system, leading to alterations in neuroendocrine pathways and immune functions, potentially facilitating tumor progression and metastasis. Understanding the immunomodulatory effects of different anesthesia techniques is crucial for optimizing perioperative care in patients with BC. The neutrophil-to-lymphocyte ratio (NLR) serves as one of the key indicators of perioperative immune response.ObjectiveTo compare the effects of inhalation anesthesia (IA) and total intravenous anesthesia (TIVA) on perioperative immune response in BC surgery patients.MethodsIn this randomized, double-blind clinical trial, BC surgery patients were randomized to receive either TIVA with propofol or IA with sevoflurane. The primary endpoint was NLR assessment. Secondary immune parameters measured included natural killer cells, various T cell subsets, B cells, the immuno-regulatory index [T-helpers (CD3+CD4+)/cytotoxic T-cells (CD3+CD8+)], matrix metallopeptidases (MMP-9), complement components, and immunoglobulins, preoperatively and at 1 and 24 hours postoperatively.ResultsThe study included 98 patients (IA: 48, TIVA: 50). The baseline characteristics exhibited remarkable similarity across the groups. No significant difference in absolute NLR values was found between IA and TIVA groups at any time point (1 hour: p = 0.519, 24 hours: p = 0.333). Decreased IgA and IgM levels post-surgery suggested potential negative impacts of IA on humoral immunity compared to TIVA. CRP levels increased more by 24 hours (p = 0.044) in IA compared to TIVA. No significant differences were observed in natural killer cells, T cell subsets, B cells, MMP-9 levels or complement components between groups. Significant differences in the immuno-regulatory index between the TIVA and IA groups at one hour postoperatively (p = 0.033) were not maintained at 24 hours.ConclusionWhile there were no notable differences in NLR among the types of anesthesia, the observed disparities in immunoglobulin content and C-reactive protein levels between groups suggest that we cannot dismiss the potential immunosuppressive effects of inhalational anesthesia in breast cancer surgeries. Further investigation needed to clarify the impact of various anesthesia methods on immune function and their implications for long-term cancer outcomes.

The aim of this study was to translate the Flourishing Scale, which is a brief 8-item measure, into Ukrainian and examine its construct validity. The Flourishing Scale has been previously validated into various languages, including Russian. While Ukrainian is a distinct language with its unique characteristics, it shares some similarities with Russian due to historical and geographical connections. These similarities encompass words with similar or related meanings, comparable sentence structures, and certain cultural references and idiomatic expressions. Accordingly, the Ukrainian version of the Flourishing Scale was developed based on the Russian version. The translation process involved two proficient researchers fluent in Ukrainian, English, and Russian. Following the committee approach, one researcher conducted the initial translation, while the other ensured the accuracy and linguistic equivalence of the translated items. The eight items were pilot-tested with Ukrainian-speaking adult participants. Results from confirmatory factor analysis indicated that the Ukrainian version of the Flourishing Scale showed evidence of construct validity and reliability, thereby resulting in a tool that can be used with Ukrainian adults to further examine their flourishing. • The Flourishing Scale was translated into Ukrainian and pilot-tested to assess it psychometric properties. • Results indicated good construct validity and reliability of the Ukrainian version of the Flourishing Scale.

Introduction:Charcot–Marie–Tooth disease type 4C (CMT4C) OMIM#601596 stands out as one of the most prevalent forms of recessive motor sensory neuropathy worldwide. This disorder results from biallelic pathogenic variants in the SH3TC2 gene.Methods:Within a cohort comprising 700 unrelated Russian patients diagnosed with Charcot–Marie–Tooth disease, we conducted a gene panel analysis encompassing 21 genes associated with hereditary neuropathies. Among the cohort, 394 individuals exhibited demyelinating motor and sensory neuropathy.Results and discussion:Notably, 10 cases of CMT4C were identified within this cohort. The prevalence of CMT4C among Russian demyelinating CMT patients lacking the PMP22 duplication is estimated at 2.5%, significantly differing from observations in European populations. In total, 4 novel and 9 previously reported variants in the SH3TC2 gene were identified. No accumulation of a major variant was detected. Three previously reported variants, c.2860C>T p. (Arg954*), p. (Arg658Cys) and c.279G>A p. (Lys93Lys), recurrently detected in unrelated families. Nucleotide alteration p. (Arg954*) is present in most of our patients (30%).

Barrier layers against intermetallic diffusion are a fundamental part on engineering electroplated coatings as they improve the lifetime of goods reducing wastes and improving the sustainability of the production chain. This study aims to set a cost-effective methodology to characterize barrier systems by evaluating the effectiveness with a recent approach based on XRF and EDS and characterize the kinetic of diffusion processes with X-ray diffractometry. Several high fashion barrier systems were tested highlighting that anticorrosion systems are not automatically suited as barrier layers for intermetallic diffusion, as opposed to industrial practice. Investigations on gold coatings obtained varying the current density revealed a correlation between the activation energy of the diffusion process, roughness, and crystallite size.

Relevance. The need to study the elemental composition of the organism of wild and domestic animals in natural environments with different levels of chemical elements. Aim. To reveal features of the elemental composition of the organism of the Altai red deer (Cervus elaphus sibiricus Severtzov, 1873), wild boar (Sus scrofa scrofa Linnaeus, 1758) and domestic pigs (Sus scrofa domesticus Erxleben, 1777) in Ongudai district, Altai Republic, including the area with signs of active geophagy. Objects. Organs and tissues of wild and domestic animals. Methods. Mass spectrometry with inductively coupled plasma; atomic-emission spectrometry; ion chromatography, analytical electron microscope with energy dispersion spectrometer. Results. The median values of chemical elements concentrations in the organisms of the Altai red deer, the wild boar and the domestic pig have been determined. S, Cl and K showed the highest values in the composition of macroelements and La, Ce, Nd and Th among rare-earth and radioactive elements. Among the elemental composition features of the studied animals, an increased accumulation of Hg and Pb in the Altai red deer; metals of the Fe-group, W, as well as rare-earth and radioactive elements – in the boar; platinoids – in the domestic pig. In comparison with the results of previous studies, increased concentrations of Hg in red deer kidneys, W in boar bronchi and Pb in the brain of domestic pigs were recorded. Assumptions were made about the factors influencing the formation of the elemental composition of the body of animals. For red deer and wild boar these are the factors of nutrition (including geophagy) and features of accumulation of elements in bone tissue; for domestic pigs – features of forage and local metallogeny, including composition of natural waters.

Background: Palliative care affords numerous benefits, including improvements in symptom management, mental health, and quality of life, financial savings, and decreased mortality. Yet palliative care is poorly understood and often erroneously viewed as end-of-life care and hospice. Barriers for better education of the public about palliative care and its benefits include shortage of healthcare providers specializing in palliative care and generalist clinicians’ lack of knowledge and confidence to discuss this topic and time constraints in busy clinical settings. Objectives: Explore and compare the knowledge, values, and practices of community-dwelling adults 19 years and older from Nebraska about serious illness and end-of-life healthcare options. Design: Secondary analysis of cross-sectional data collected in 2022 of 635 adults. We examined the fifth wave (2022) of a multiyear survey focusing on exploring Nebraskans’ understanding of and preferences related to end-of-life care planning. Methods: Descriptive statistics and chi-square tests to compare results between groups. Univariable and multivariable logistic regression analyses examine associations of variables as to knowledge of hospice and palliative care. Results: While 50% of respondents had heard a little or a lot about palliative care, 64% either did not know or were not sure of the difference between palliative care and hospice. Those who reported being in poor health were not more likely to know the difference between palliative care and hospice compared to those reporting being in fair, good, or excellent health. Conclusion: This study offers insight into the knowledge and attitudes about palliative care among community-dwelling adults, 19 years and older living in Nebraska. More effort is needed to communicate what palliative care is, who can receive help from it, and why it is not only for people at end of life. Advance care planning discussions can be useful in offering clarity.

Introduction: Over the recent decades, the importance of Urinary Tract Infections (UTI) has been increasingly recognised in children. The occurrence of UTI during childhood may lead to acute and/or chronic consequences, such as impaired renal function, renal scarring, and hypertension. Due to the irrational use of antimicrobials, multidrug resistant bacterial strains are frequent. Hence, there is an urgent need for continuous surveillance of the microbiological profile of UTI. Aim: To investigate the microbial profile and antibiotic sensitivity pattern from the urine of paediatric patients suspected to have UTI in Idukki district, Kerala and to explore its association with seasonal variations. Materials and Methods: This clinical cross-sectional study was conducted in Al Azhar Medical College and Super Specialty Hospital, Thodupuzha, Idukki, Kerala, India, from January 2019 to December 2021. The study involved 882 paediatric patients in the age group 0-15 years with symptoms and signs suggestive of UTI. Data regarding age, gender, season, laboratory and culture results, and antibiotic sensitivity pattern were considered as variables of interest. Analysis was performed using mean and standard deviation for quantitative variables, and frequency and proportion for categorical variables. The statistical analyses were conducted using Statistical Package for Social Sciences (SPSS) version 20.0 and Microsoft Excel 2010. Results: The study involved 882 patients, of which 399 were males (45.2%) and 483 were females (54.8%) with a male-to-female ratio of 0.8:1. The mean age of patients was four years, and a peak incidence was observed in children in the age group of 1-3 years, with 333 (37.8%) children. Microbial growth was observed in the urine of 325 (36.8%) patients. After excluding normal commensal perineal flora and insignificant bacteriuria, 233 samples had significant growth, with males accounting for 106 (45.5%) and females 127 (54.5%). The male-to-female ratio was 0.8 to 1. These samples mostly exhibited growth of aerobic bacteria (232, 99.6%) and Candida albicans (1, 0.4%). E. coli (106, 45.5%) was identified as the most predominant aetiological agent for paediatric UTI. Conclusion: The results of this study suggest that it would be advisable for paediatricians in Idukki district to refrain from using Ampicillin to treat cases suspected to have UTI. Preventive measures should be advised to all patients, with emphasis on urinary hygiene during the monsoon and winter seasons.

Analyses of inequalities related to prevention and cancer therapeutics/care show disparities between countries with different economic standing, and within countries with high Gross Domestic Product. The development of basic technological and biological research provides clinical and prevention opportunities that make their implementation into healthcare systems more complex, mainly due to the growth of Personalized/Precision Cancer Medicine (PCM). Initiatives like the USA‐Cancer Moonshot and the EU‐Mission on Cancer and Europe's Beating Cancer Plan are initiated to boost cancer prevention and therapeutics/care innovation and to mitigate present inequalities. The conference organized by the Pontifical Academy of Sciences in collaboration with the European Academy of Cancer Sciences discussed the inequality problem, dependent on the economic status of a country, the increasing demands for infrastructure supportive of innovative research and its implementation in healthcare and prevention programs. Establishing translational research defined as a coherent cancer research continuum is still a challenge. Research has to cover the entire continuum from basic to outcomes research for clinical and prevention modalities. Comprehensive Cancer Centres (CCCs) are of critical importance for integrating research innovations to preclinical and clinical research, as for ensuring state‐of‐the‐art patient care within healthcare systems. International collaborative networks between CCCs are necessary to reach the critical mass of infrastructures and patients for PCM research, and for introducing prevention modalities and new treatments effectively. Outcomes and health economics research are required to assess the cost‐effectiveness of new interventions, currently a missing element in the research portfolio. Data sharing and critical mass are essential for innovative research to develop PCM. Despite advances in cancer research, cancer incidence and prevalence is growing. Making cancer research infrastructures accessible for all patients, considering the increasing inequalities, requires science policy actions incentivizing research aimed at prevention and cancer therapeutics/care with an increased focus on patients' needs and cost‐effective healthcare.

The aim of the study was to determine the spread of SARS-CoV-2 among students of Medical University-Pleven during the fourth wave of the COVID pandemic by PCR testing and to analyze epidemiological data. Material and methods: Cross-sectional epidemiological study was conducted for the period November-December 2022. A sociological method of data collection (interview) was used, and a questionnaire was developed for this purpose. Nasopharyngeal swab was taken from the students and RT-PCR analysis of SARS-CoV-2 was performed. Results: An interview was conducted with 200 students from various specialties at Medical University-Pleven. Clinical symptoms were reported by 24 (12%) of respondents, the leading ones being runny nose and cough; with comorbid conditions were 10 participants (5%) with predominant chronic lung diseases. Three students reported contact with coronavirus-positive patients. Six of the participants had travelled abroad in the past 14 days. Eighty-four students (42%) were immunized: 25 with one dose, 43 with two doses and 16 with three doses. Only two tested samples (1%) were positive for SARS-CoV-2. Both subjects reported complaints at the sampling time and were unvaccinated. Conclusion: The results of the study show a low percentage of infected, mostly non-immunized persons, which coincides with the trend in Bulgaria during the fourth wave of the COVID pandemic.

The term "Unhappy Triad", coined by O'Donoghue, reflects a severe knee injury with rupture of the medial collateral ligament, medial meniscus, and anterior cruciate ligament. The triad is primarily a sports injury, and patients' recovery is 6 to 12 months. Material/Methods: 70 patients with "O'Donoghue's triad" were studied. Total anterior cruciate ligament rupture was reconstructed with patellae ligament autograft; medial meniscus tear was treated with partial meniscectomy; and medial collateral ligament injury was treated conservatively at 1 month before surgery. The aim of the study is to establish the epidemiology of the injury: age and gender distribution, distribution by types of sports in patients with "O'Donoghue's Triad" after arthroscopic treatment. 222 persons were examined in two stages – first, 187 with various soft tissue injuries of the knee, after surgical treatment, including persons with the triad, and second, 70 patients with O'Donoghue's triad. Results: The study shows that among 18-19-year-olds, the triad was found in 4 people; from 20 to 29 in 34, from 30 to 39 in 23, and from 40 to 49 in 9. In terms of gender, there were 62 men (86.11%) and 8 women (13.89%) with the triad injury. "O'Donoghue's Triad" was obtained during sports in 91.52% of cases, the remaining 8.48% in car accidents and household accidents. Conclusions: The results of the study establish and provide coaches, physiotherapists, orthopedists, scientists and educators with up-to-date data on the epidemiology of O'Donoghue's Triad, its incidence, age and sex characteristics and its distribution by sport.

Purpose: The aim of the study was to follow the influence of the Ergon Technique on proprioception in patients after surgical treatment of bimalleolar ankle fracture. Material/Methods: 30 patients with a bimalleolar fracture in the subacute postoperative period were studied, divided as follows: control group (CG) - 15 patients and experimental group (EG) - 15 patients. In CG, a traditional model of kinesitherapy is applied, and in EG, an experimental model is applied, which includes twice a week and Ergon Technique. To monitor changes in proprioception, a test was conducted: a balanced stance on the injured leg on a hard and flat surface was performed, and the time the patient maintained balance (in seconds) was recorded. Results: The mean values (±SD) after one month of kinesitherapy application are as follows: in the control group 0,9333+0,88 sec. and 3,0 sec. in the experimental group. After three months of treatment, the results are as follows: in the control group, 3,93+2,49 sec. And 9,2+4,19 sec. in the experimental group. The values of P show that the established difference in the mean values ​​of the indicator in the two groups after three months of kinesitherapy is statistically significant and proves a higher efficiency of the experimental model compared to the traditional one applied in the control group at P

Introduction: The worldwide application of digital technology has presented dentistry with transformative opportunities. The concept of digital dentures, incorporating computer-aided design (CAD) and computer-aided manufacturing (CAM) techniques, holds the promise of improved precision, customization, and overall patient satisfaction. However, the shift from traditional dentures to their digital counterparts should not be taken lightly, as the intricate interplay between oral physiology, patient comfort, and long-term durability requires thorough examination. Aim: The aim of the present study was to evaluate and compare the dimensional changes of 3D printed (NextDent, 3D Systems, The Netherlands) and conventional heat-cured (Vertex BasiQ 20, 3D Systems, The Netherlands) denture base resin after immersion in artificial saliva for different periods (7, 14, and 30 days) and then applying 3D simulated deformation, tensional strength, and stress, using the ANSYS software (ANSYS Inc., Pennsylvania, USA). Materials and methods: For the manufacturing of the test specimens, an STL file was created, using the Free CAD Version 0.19 (Free CAD, Stuttgart, Germany). The dimensions of each specimen were 20 mm in width, 20 mm in length, and 3 mm in thickness. Two hundred experimental bodies were created and divided into two groups (n=100), with half fabricated using a 3D printer (NextDent 5100, NextDent, 3D Systems, The Netherlands) and the other half prepared using the traditional method of heat-curing polymerization in metal flasks. The test samples were then weighed using an analytical balance, immersed in artificial saliva for three periods (7, 14, and 30 days), and reweighed after water absorption. After desiccation at 37°C for 24 hours and then at 23±1°C for 1 hour, the samples were weighed again. Then the data were entered into the specialized program ANSYS and the 3D simulation tests for deformation, tension, and stress were performed. Statistical analysis was performed using the IBM SPSS Statistics Version 0.26 statistical software, which includes descriptive statistics and one-way ANOVA analysis. Results: The findings weren’t statistically significant and indicated that the average metrics for the 3D-printed experimental test samples were marginally greater than those recorded for the conventional samples. Conclusions: Within the limitations of this study, it is possible to conclude that 3D-printed resin has a lower capacity to withstand deformation, tension, and stress under simulated conditions than conventional dental resin. However, they do not exceed the values accepted by the ISO standard for clinical application of this type of material.

The specific share of the reserves of hard-to-recover hydrocarbon raw materials is steadily growing. The search for technologies to increase the hydrocarbon recovery factor is one of the most urgent tasks facing the oil and gas industry. One of the methods to expand the coverage of oil reserves and increase oil recovery is to use the technology of drilling multilateral wells with a fishbone trajectory. In the Russian Federation, the most branched well was drilled in the Republic of Sakha (Yakutia) at the Srednebotuobinskoye oil and gas condensate field. The main object of development is the Botuobinsky horizon (Bt reservoir). About 75 % of the geological reserves of the reservoir are concentrated in a thin oil rim with an average oil-saturated layer thickness of 10 m with an extensive gas cap. This circumstance is one of the main complicating factors in the development of the Srednebotuobinskoye oil and gas condensate field. For such complex wells, one of the most important design stages is to determine the optimal location of the fishbone well in an oil-saturated reservoir. The article shows the results of sector modeling in the conditions of the Srednebotuobinskoye field to determine the optimal location of multilateral wells using Tempest simulator.

Abstract The Caucasus region is key for understanding early human dispersal and evolution in Eurasia, and characterizing the environmental contrast between Last Glacial Maximum and Holocene is crucial for investigating human adaptation strategies to large climatic shifts. However, a paucity of high-resolution paleoclimate records leave this context largely unknown for early human populations in the Caucasus region. Based on our model-proxy comparison of high- and low-resolution records of 24 stalagmites from three caves, we find spatially distinct changes in vegetation and seasonality of precipitation, especially under glacial conditions. Supported by modern oxygen-isotope data and climate modeling, we identify a supraregional cold-season temperature control for oxygen isotopes in Black Sea speleothems, which previously had been interpreted as a local moisture-source signal. Carbon-isotope and trace-element data further suggest disproportionate changes in vegetation cover and soil dynamics at high altitudes, which would have resulted in a reduction but not a disappearance of human refugia during the Last Glacial Maximum, relative to the current interglacial. Our findings imply that abrupt climatic pressures from harsh conditions were overcome by adaptive strategies in the past.

This study aimed to evaluate prognostic values of the serum lipid panel data for development of macrovascular complications (MVC) in patients with type 2 diabetes mellitus (T2DM) alone and those with comorbid hypothyroidism (HT), diff use non-toxic goiter (DNTG), or a combination of these disorders. Th e study included 596 inpatients. Receiver operating characteristic (ROC) analysis was used to identify prognostically signifi cant values of total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), non-HDL-cholesterol (non-HDL-C) and remnant cholesterol (RC). Th e following cut-off points that determine the relative risk of MVC development were established: TC >5.11 mmol/L, TG ≥2.03 mmol/L, LDL-C ≥2.97 mmol/L and non-HDL-C ≥4.29 mmol/L in T2DM patients with comorbid HT; TC ≥4.97 mmol/L, TG ≥2.54 mmol/L, LDL-C ≥3.21 mmol/L and non-HDL-C ≥4.20 mmol/L in T2DM patients with comorbid DNTG; and TC ≥4.89 mmol/L, TG ≥1.56 mmol/L, LDL-C ≥2.93 mmol/L, non-HDL-C ≥4.04 mmol/L and RC ≥1.14 mmol/L in those with comorbid HT and DNTG. Th us, serum levels of TC, TG, LDL-C, non-HDL-C and RC can be used for stratification of T2DM patients with comorbid thyroid dysfunction into the category of increased risk of MVC development.

This extensive 10-year study conducted in Northern Kazakhstan investigates the intricate relationship between soil management techniques, crop rotations, and soil organic matter (SOM) content in Chernozem soils, an essential agricultural resource in the region. The experiments were established at the Karabalyk Agricultural Experimental Station, characterized by a arid continental climate. The study systematically examined the impact of two primary soil management techniques, conventional tillage (CT) and no-tillage (NT), in combination with various crop rotations. The crop rotations tested included grain-fallow rotations, fruit-exchange crop rotations, and an eight-field fruit-exchange crop rotation. The results provide valuable insights into the sustainable management of Chernozem soils in arid conditions, underscoring the role of crop rotation strategies in preserving SOM content. The findings reveal that among the crop rotations tested, the eight-field fruit-exchange crop rotation exhibited the most favorable outcomes for SOM preservation. This rotation helped maintain relatively stable SOM levels over the 10-year study period, contributing to soil health and fertility. In the context of the region's arid climate, the choice of soil management technique (CT or NT) had a limited impact on SOM content. The stability of SOM levels across diverse crop rotations and years highlights the dominant influence of crop management practices in this distinctive agricultural environment. This research serves as a valuable reference for tailored approaches to ensure soil health and organic matter preservation in the unique conditions of Northern Kazakhstan. It promotes the adoption of diversified crop rotations, with particular emphasis on the effectiveness of the eight-field fruit-exchange crop rotation, as a powerful strategy to mitigate organic matter loss, enhance soil quality, and optimize soil fertility in arid agricultural landscapes. The insights gained from this study are vital for sustainable land management in the region and underscore the importance of region-specific, holistic investigations to guide effective agricultural practices. The findings offer a solid foundation for the development of strategies that address soil health and safeguard the integrity of essential soil resources in these unique environments. The study conducted at the Karabalyk Agricultural Experimental Station in Northern Kazakhstan between 2011 and 2021 provides critical insights into the relationship between soil management techniques, crop rotations, and SOM content in Chernozem soils. The research suggests that diversified crop rotations, particularly the eight-field fruit-exchange crop rotation, represent a promising approach for mitigating organic matter loss and enhancing soil quality in arid regions.

Abstract Vascular permeability is mediated by Cortactin (Cttn) and regulated by several molecules including cyclic-adenosine-monophosphate, small Rho family GTPases and the actin cytoskeleton. However, it is unclear whether Cttn directly interacts with any of the junctional components or if Cttn intervenes with signaling pathways affecting the intercellular contacts and the cytoskeleton. To address these questions, we employed immortalized microvascular myocardial endothelial cells derived from wild-type and Cttn-knock-out mice. We found that lack of Cttn compromised barrier integrity due to fragmented membrane distribution of different junctional proteins. Moreover, immunoprecipitations revealed that Cttn is within the VE-cadherin-based adherens junction complex. In addition, lack of Cttn slowed-down barrier recovery after Ca2+ repletion. The role of Cttn for cAMP-mediated endothelial barrier regulation was analyzed using Forskolin/Rolipram. In contrast to Cttn-KO, WT cells reacted with increased transendothelial electrical resistance. Absence of Cttn disturbed Rap1 and Rac1 activation in Cttn-depleted cells. Surprisingly, despite the absence of Cttn, direct activation of Rac1/Cdc42/RhoA by CN04 increased barrier resistance and induced well-defined cortical actin and intracellular actin bundles. In summary, our data show that Cttn is required for basal barrier integrity by allowing proper membrane distribution of junctional proteins and for cAMP–mediated activation of the Rap1/Rac1 signaling pathway.

Abstract Background Generating rigorous evidence to inform care for rare diseases requires reliable, sustainable, and longitudinal measurement of priority outcomes. Having developed a core outcome set for pediatric medium-chain acyl-CoA dehydrogenase (MCAD) deficiency, we aimed to assess the feasibility of prospective measurement of these core outcomes during routine metabolic clinic visits. Methods We used existing cohort data abstracted from charts of 124 children diagnosed with MCAD deficiency who participated in a Canadian study which collected data from birth to a maximum of 11 years of age to investigate the frequency of clinic visits and quality of metabolic chart data for selected outcomes. We recorded all opportunities to collect outcomes from the medical chart as a function of visit rate to the metabolic clinic, by treatment centre and by child age. We applied a data quality framework to evaluate data based on completeness, conformance, and plausibility for four core MCAD outcomes: emergency department use, fasting time, metabolic decompensation, and death. Results The frequency of metabolic clinic visits decreased with increasing age, from a rate of 2.8 visits per child per year (95% confidence interval, 2.3–3.3) among infants 2 to 6 months, to 1.0 visit per child per year (95% confidence interval, 0.9–1.2) among those ≥ 5 years of age. Rates of emergency department visits followed anticipated trends by child age. Supplemental findings suggested that some emergency visits occur outside of the metabolic care treatment centre but are not captured. Recommended fasting times were updated relatively infrequently in patients’ metabolic charts. Episodes of metabolic decompensation were identifiable but required an operational definition based on acute manifestations most commonly recorded in the metabolic chart. Deaths occurred rarely in these patients and quality of mortality data was not evaluated. Conclusions Opportunities to record core outcomes at the metabolic clinic occur at least annually for children with MCAD deficiency. Methods to comprehensively capture emergency care received at outside institutions are needed. To reduce substantial heterogeneous recording of core outcome across treatment centres, improved documentation standards are required for recording of recommended fasting times and a consensus definition for metabolic decompensations needs to be developed and implemented.

Abstract Background Although disaster risk reduction (DRR) addresses underlying causes and has been shown to be more cost-effective than other emergency management efforts, there is lack of systematized DRR categorization, leading to insufficient coherence in the terminology, planning, and implementation of DRR. The aim of this study was to conceptualize and test a novel integrated DRR framework that highlights the intersection between two existing classification systems. Methods Grounded theory was used to conceptualize a novel DRR framework. Next, deductive conceptual content analysis was used to categorize interventions from the 2019 Cities100 Report into the proposed DRR framework. The term “connection” indicates that an intervention can be categorized into a particular section of the novel integrated approach. A “connection” was determined to be present when the intervention description stated an explicit connection to health and to the concept within one of the categories from the novel approach. Further descriptive statistics were used to give insight into the distribution of DRR interventions across categories and into the application of the proposed framework. Results The resulting framework contains nine intersecting categories: “hazard, prospective”, “hazard, corrective”, “hazard, compensatory”, “exposure, prospective”, “exposure, corrective”, “exposure, compensatory”, “vulnerability, prospective”, “vulnerability, corrective”, and “vulnerability, compensatory”. The thematic analysis elucidated trends and gaps in the types of interventions used within the 2019 Cities100 Report. For instance, exposure-prospective, exposure-compensatory, and vulnerability-compensatory were the most under-utilized strategies, accounting for only 3% of the total interventions. Further descriptive statistics showed that upper middle-income countries favored “hazard, corrective” strategies over other DRR categories while lower middle-income countries favored “exposure, corrective” over other DRR strategies. Finally, European cities had the highest percentage of DRR connections (51.39%) compared to the maximum possible DRR connections, while African cities had the lowest percentage of DRR connections (22.22%). Conclusions The study suggests that the proposed DRR framework could potentially be used to systematically evaluate DRR interventions for missing elements, aiding in the design of more equitable and comprehensive DRR strategies.

Located at the intersection of scholarship on critical higher education (HE), the casualisation of the academic workforce and studies of digitalisation and online platforms in Higher Education (HE), this article examines the impact of online programme management companies (OPMs) on academic labour. OPMs partner with universities to provide core teaching functions while relying on the labour of increasingly casualised, often outsourced academics. We use a composite case study to illustrate how OPMs work in partnerships with universities to reorganise academic work. We discuss this model vis-a-vis the theoretical concepts in the digital HE, platform labour and sociology of work literature, elaborating on how the new forms of casualised labour in HE undergo real subsumption by technology-mediated programmes operated by OPMs. On this foundation, we discuss the possible implications and draw out questions for future research and trade union activity, two arenas where, we argue, more attention needs to be paid urgently to casualisation and the outsourcing of teaching through digital platform-mediated programmes.

The article underlines the importance of effective implementation of the state national policy for the stability and sustainability of the state. This issue is particularly relevant in the context of such large ethno-linguistic communities as the Turkic peoples, which are vulnerable to external influence objects. The authors consider the issue of foreign influence on the territorial units of the Russian Federation through economic and humanitarian spheres on the example of the activities of the Republic of Turkey. Within the framework of the ideology of pan-Turkism, the Turkic-speaking peoples, especially those living on the territory of the Russian Federation, are of particular importance to Turkey. Ankara justifies interference in the internal affairs of sovereign states with the idea of building a “Turkic world” under the auspices of Turkey. The article reflects the activities of Turkish organizations, as well as the specifics of economic and humanitarian cooperation in the Republics of Tatarstan, Bashkortostan, Chuvashia, Crimea, Altai, Sakha (Yakutia), Tyva, Khakassia. The analysis of open sources and official data revealed the degree of intensity of the Turkish presence in the Turkic-speaking regions. In the Volga Federal District, the level of Turkish influence as well as cooperation in various fields is quite high, especially in Tatarstan and Bashkortostan. The Republic of Chuvashia remains the least susceptible to Turkish destructive activity. The informational impact through the pro-Turkish media is mainly observed in the Republic of Crimea. In Altai, Tuva and Khakassia, after 2015, the activity of interaction with Turkey in the humanitarian and economic spheres has decreased to some extent. However, the designation of the factor of external influence and the development of effective measures to counteract it should become one of the most important topics of the new Strategy of the state national policy after 2025.

The countries of South Asia are among the most densely populated on the planet. Active migration processes are observed in the region, which have an impact on the socio-economic development of countries. The statistical data and reports of the International Organization for Migration of the United Nations served as an empirical basis for studying the migration mobility of the population of the countries of South Asia. The study is based on information on the structure of emigration and immigration of India, Bangladesh, Pakistan and Afghanistan in absolute and relative terms. For greater clarity, a cartographic method was used: author’s maps were created that reflect the specifics of migration processes in the countries of South Asia in terms of absolute and relative indicators. The scientific base concerning economic and social development of India, Bangladesh, Pakistan and Afghanistan is systematized. The study revealed the specifics of migration flows in the countries of the region on the basis of statistical information on the emigration and immigration of citizens, calculated in absolute and relative terms. The factors influencing the migration mobility of the population are revealed. A retrospective analysis of migration processes in India, Bangladesh, Pakistan and Afghanistan was carried out to identify similar and different features in their history that continue to influence the current migration processes taking place in the region. The reasons for the popularity of India among migrants from neighboring countries of South Asia are substantiated. The influence of the heritage of British India on modern interstate processes in South Asia is shown. The differentiation of intraregional and interregional migration flows in South Asia is analyzed. An assessment is made of the impact of migration processes on the socio-economic development of India, Bangladesh, Pakistan and Afghanistan. The characteristics of the current features in the migration situation in the countries of South Asia are formulated.

The author deals with the question of Chkhartishvili’s pen names and their role in his work. The characteristics of literary masks, history of their appearance are presented. A general analysis of Chkhartishvili's literary activity and the evolution of his style is also given. The features of the use of various images “tried on” by the writer when creating the main works are analyzed, the necessity of referring to pseudonyms is justified. The main part of the work is devoted to the problem of authorship in the project History of the Russian State, as well as an explanation of the motives that guide G. Chkhartishvili, publishing a historical work under the pseudonym of Boris Akunin. An assessment of Akunin's writing style, his ability to transform familiar genres to the needs of the audience, time, author's tasks, etc., is presented, and the project's fiction texts are overall analyzed. Conclusions are made about the literary image of Chkhartishvili-Akunin as an alternative hero involved in the creation of a historical project. This fact suggests that the writer once again demonstrates his ability to reincarnate, change plot and style and, of course, transform the manner of writing, when working on a particular work of fiction.

The red mullet (Mullus barbatus Linnaeus, 1758) is a keynote species for the Bulgarian Black Sea ecosystem and fisheries; nevertheless, existing knowledge on population status is very scarce. The present study was intended to assess the health status and adaptive potential of M. barbatus populations inhabiting the Bulgarian waters of the Black Sea. Our findings revealed that populations of M. barbatus are exposed to a variety of anthropogenic and environmental stressors. The species’ status was assessed using representative genetic, morphological, biochemical and chemical biomarkers from specimens obtained in the research area’s northern and southern regions. Based on mtDNA markers, genetic analysis revealed low haplotype and nucleotide diversity, typically observed in overexploited or “threatened” populations. Examining the morphology of the specimens revealed no discernible pattern of differentiation. Except for aluminium and chrome, metal and PAH concentrations in fish were below the regulatory thresholds. The specimens from the southern region ingested more microplastics than those from the northern region. The majority of specimens collected from the southern region also exhibited elevated levels of oxidative stress and decreased antioxidant defence, which can be interpreted as an early indication that they had reached the limits of their adaptive potential. Further research on the composite effects of the stressogenic environment on the Black Sea biota are critically needed, as well as the introduction of new indicators and thresholds at molecular and cellular levels for adequate monitoring of both the ecological state of the marine environment and its biota.

Background and Aim: Mastitis is recognized as the most common disease in cattle and causes economic losses in the dairy industry. A number of opportunistic bacterial taxa have been identified as causative agents for this disease. Conventionally, antibiotics are used to treat mastitis; however, most bacteria are resistant to the majority of antibiotics. This study aimed to use molecular methods to identify milk microbiome patterns characteristic of mastitis that can help in the early diagnosis of this disease and in the development of new treatment strategies. Materials and Methods: To evaluate the microbiome composition, we performed NGS sequencing of the 16S rRNA gene of the V3 region. Results: An increase in the abundance of the bacterial genera Hymenobacter and Lachnospiraceae NK4A136 group is associated with the development of subclinical and clinical mastitis in dairy cows. These bacteria can be added to the list of markers used to detect mastitis in cows. Furthermore, a decrease in the abundance of Ralstonia, Lachnospiraceae NK3A20 group, Acetitomaculum, Massilia, and Atopostipes in cows with mastitis may indicate their role in maintaining a healthy milk microbiome. Antibiotics reduced the levels of Streptococcus in milk compared to those in the healthy group and cows before antibiotic treatment. Antibiotic therapy also contributed to an increase in the abundance of beneficial bacteria of the genus Asticcacaulis. Conclusion: This study expands our understanding of the association between milk microbiota and mastitis.

Abstract Background and objectives Limb ischemia or compartment syndrome, requiring surgery, are some of the frequent cannula-related complications in patients supported with veno-arterial extracorporeal membrane oxygenation (VA-ECMO). The purpose of this exploratory study is to depict and evaluate the dynamic changes in the lower limb muscles with ultrasound shear wave elastography as marker for early lower limb ischemia. Methods Eleven patients with VA-ECMO after cardiac arrest were included in this study. Seven patients received distal perfusion cannula (DPC) after implantation of the VA-ECMO, whereas 4 had no DPC after VA-ECMO. Compartment syndrome was clinically excluded in all patients. Both lower limbs, e.g., with and without arterial cannula, were monitored with near-infrared spectroscopy (NIRS) for the oxygen saturation of the local tissue. We performed ultrasound shear wave elastrography (SWE) to assess dynamic changes of the medial gastrocnemius muscle at maximum passive muscle stretch (exercise) of both legs. Color-coded duplexsonography was conducted to examine the blood flow velocity of the popliteal artery of the lower limb. Results We found no difference between DPC and no DPC (p = 0.115) during use of VA-ECMO. However, we detected marked lower limb muscle perfusion deficits of cannulated (58.9 ± 13.5 kPa) vs. cannula-free limb (95.7 ± 27.9 kPa: p

The national security depends on the health of the population, which, in its turn, depends on the healthcare system. After the collapse of the Soviet Union, Russia focused on the primary healthcare. The goals, tools, and results of the reforms that have taken place in the last three decades are usually considered from the point of view of law, economic feasibility, or organizational effectiveness. The author applied the historical and political approach to these reforms, thus evaluating their ability to preserve and increase human health. Fertility, morbidity, and mortality usually serve as national health criteria. The research relied on regulatory legal acts, speeches of senior government officials, official statistics, and sociological surveys. Demographic problems and budget deficits proved to be the main reasons behind the post-Soviet reforms, which transferred some material obligations from the federal to the local level and expended the scope of commercial medicine. Part of the financial burden moved from expensive specialized hospitals (secondary healthcare) to cheaper polyclinic and preventive medicine (primary healthcare). Federal budget expenditures decreased as patient capacity and the number of medical organizations went down and the productivity of primary healthcare went up. However, the national mortality and morbidity kept growing. The current diagnostic preventive healthcare model concentrates on primary healthcare: it reduces financial expenditures but fails to solve the demographic problems.