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Purpose. To study environmental crimes in the field of subsurface resources protection and provide their criminological characterization, namely, to determine criminological indicators reflecting the studied crime rate, dynamics and structure. Methodology. A system of general scientific and special methods and approaches ensuring an objective analysis of the studied issue, particularly, logical and dogmatic, systematic, documentary, and modeling and statistical analysis methods. Findings. We determined absolute, mean and relative indicators of environmental crimes in the field of subsurface resources protection in Ukraine during 2002–2021, their total recorded number (9118 crimes), annual average (456 crimes) and share in the overall crime structure over the past 20 years (0.1 %). The conclusion shows a significant growth of environmental crimes in the field of subsurface resources protection in the overall crime structure (from 0.01 to 0.24 %) due to a significantly higher increase in these crimes rate compared to the absolute overall crime rate. The calculated dynamics indicators showed wave-like changes in the recorded crimes number against their steady overall upward trend – over the twenty-year period analyzed, reported crimes of this category increased more than 14 times. Originality. Following a long-term statistical analysis, since illegal amber mining criminalization, the article provides the first criminological characterization of environmental crimes in the field of subsurface resources protection. Practical value. The authors substantiate their understanding of the essence of this crime category envisaged by Article 240 of Ukraine’s Criminal Code “Violation of the Rules for Subsurface Resources Protection or Use, Illegal Extraction of Mineral Resources” and Article 2401 of Ukraine’s Criminal Code “Illegal Mining, Sale, Acquisition, Transfer, Sending, Transportation, and Processing of Amber”. The calculated indicators of the rate, dynamics and structure of the studied crimes are of standalone significance for academic research and law enforcement activities and create an appropriate basis for the information provision of combating environmental crimes in the field of subsoil protection being a prerequisite for developing an appropriate system of specified crime prevention measures.

The purpose of the research was to scientifically substantiate the conceptual approaches to the development of normative document on drinking water quality in order to prevent morbidity and mortality in martial law during armed aggression in Ukraine and other emergencies. Materials and methods: descriptive, sanitary-chemical, normative-search, comparative analysis, expert assessments have been used. The paper analyzes the results of observations of efficiency and monitoring of water quality from water supply stations of Ukraine before and after the war, and compare assessment of the main provisions of regulations on drinking water quality of some countries, including those used in emergencies. Results. The research established that in wartime centralized drinking water supply companies are burdened by problems due to unguaranteed quality of source water, lack of stable conditions for the technological process of water treatment, operation or destruction of water treatment plants and networks etc. Current standards in Ukraine( DSanPiN 2.2.4-171-10 "Hygienic requirements for drinking water intended for human consumption") during martial law require significant changes: supplementation of safety and quality indicators due to the new risks of drinking water pollution; exclusion of certain safety and quality indicators at the expense of non-priority ones; establishment of temporary hygienic standards for tap water and water dispensing points and the procedure for their use; adjusting the frequency of production control of potable water; implementation preventive measures to reduce morbidity and mortality. Today the project of “DSanPiN "Safety indicators and some particular indicators of potable water quality during martial law and emergencies of another nature" (hereinafter - DSanPiN) has been scientifically substantiated and developed. According to the draft of this document, the quality of drinking water in terms of epidemic and radiation safety must meet the requirements of DSanPiN 2.2.4-171; in terms of physicochemical - see requirements of DSanPiN. The requirements of DSanPiN after their state registration will be applied during martial law and during emergencies of other nature in a particular area for a specified period as short as possible by the relevant regional or local commission for technogeneous environmental safety and emergencies. Conclusions. It is established that during the military emergency situation in Ukraine the current DSanPiN 2.2.4-171-10 "Hygienic requirements for potable water intended for human consumption" require significant changes in order to: supplement safety indicators due to the emergence of new risks of drinking water pollution; exclude certain indicators of safety and quality due to non-priority; establish temporary hygienic standards for potable tap water and bottling points in personal containers of consumers and the procedure for their use; adjust the frequency of production control of potable water quality; implement other preventive measures to reduce morbidity and mortality.. Nowadays the draft DSanPiN "Safety indicators and some indicators of potable water quality in martial law and emergencies of other nature" is scientifically substantiated and developed, and it was submitted to the Ministry of Justice of Ukraine for state registration.

The article examines transformation of the legal regulation of flexible working hours, home-based work and teleworking in Ukraine in the context of the experience of foreign countries during the COVID-19 pandemic. It is investigated that under quarantine conditions the application of these forms of labour organization has increased and their legislative regulation in Ukraine and foreign countries has improved. Currently, in Ukraine flexible working hours are applied not only to employees who work under an employment contract, but also to government employees. The legal regulation of home-based work and teleworking has undergone some transformations from their initial identification to the subsequent differentiation. Legislative consolidation of teleworking has led to the establishment of a new institution, namely the right to disconnect (the period of free time of the employee who works remotely). Comparative characteristics of flexible working hours, home-based work and teleworking according to the laws of Ukraine are identified. It has been found that the legalization of non-traditional forms of labour organization including flexible working hours, home-based work and teleworking under quarantine conditions has allowed maintaining the stability of labour relations, ensuring social distance of workers and reducing the morbidity level during the COVID-19 pandemic.

The article examines the issue of innovative financial technologies in the context of the digital economy. The leading foreign experience of investing in fintech companies was analyzed, and the dynamic development of financial technologies was proven based on the analysis of statistical data. The main features of fintech companies are revealed. Quantitative and qualitative methods (the method of discounted cash flows, the first Chicago method and the Berkus method) of company value estimation, which are better than others, are able to take into account the peculiarities of the fintech industry, are considered. It has been proven that the optimal valuation method for mature fintech companies is the discounted cash flow method and the first Chicago method. A qualitative assessment of the Ukrainian fintech startup was also carried out using the Berkus method.

Background. Identifying biomarkers of inflammation in traumatic brain injury (TBI) can be a valuable factual complement to improving the quality of prediction for brain injury outcomes. One such marker may be tumor necrosis factor alpha (TNF-α), which belongs to the group of proinflammatory cytokines. The purpose was to evaluate the effect of ademol compared with amantadine sulfate on TNF-α level in the brain of TBI rats. Materials and methods. The experiments were performed on male rats. An experimental model of severe TBI was created using a pneumatic gun. The therapeutic effect of ademol in TBI was evaluated at a dose of 2 mg/kg intravenously twice a day for 8 days. As the drug for the control group, 0.9% NaCl was used at a dose of 2 ml/kg, and as the comparison drug — amantadine sulfate at a dose of 5 mg/kg. The level of TNF-α was used to determine the efficacy of the investigated drugs. Results. A comparative analysis of the efficacy of ademol and amantadine sulfate on day 8 of observation showed that in the group of animals treated with ademol, the content of TNF-α in brain tissues has reduced by 57.3 % (p, Актуальность. Выявление биомаркеров воспаления в условиях черепно-мозговой травмы (ЧМТ) может стать ценным дополнением к улучшению качества прог­нозирования исходов травмы головного мозга. Одним из таких маркеров может быть фактор некроза опухоли альфа (TNF-α), который относится к группе провоспалительных цитокинов. Цель: оценить влияние адемола по сравнению с амантадина сульфатом на уровень TNF-α в головном мозге крыс с ЧМТ. Материалы и методы. Опыты проведены на крысах-самцах. Экспериментальную модель тяжелой ЧМТ создавали с использованием пневматического пистолета. Терапевтическое действие адемола при ЧМТ оценивали в дозе 2 мг/кг с интервалом 2 раза в день в течение восьми суток. В качестве лекарственного средства для контрольной группы применяли 0,9% NаСl в дозе 2 мл/кг, а препарата сравнения — амантадина сульфат в дозе 5 мг/кг. Для определения эффективности исследуемых препаратов использовали уровень TNF-α. Результаты. Сравнительный анализ эффективности адемола и амантадина сульфата на восьмые сутки наблюдения показал, что в группе животных, у которых применяли адемол, содержание TNF-α в тканях мозга оказалось меньше на 57,3 % (р, Актуальність. Виявлення біомаркерів запалення в умовах черепно-мозкової травми (ЧМТ) може стати цінним доповненням до поліпшення якості прогнозування фіналів травми головного мозку. Одним із таких маркерів може бути фактор некрозу пухлини альфа (TNF-α), який належить до групи прозапальних цитокінів. Мета: оцінити вплив адемолу порівняно з амантадину сульфатом на рівень TNF-α в головному мозку щурів із ЧМТ. Матеріали та методи. Дослідження проведено на щурах-самцях. Експериментальну модель тяжкої ЧМТ створювали з використанням пневматичного пістолета. Терапевтичну дію адемолу при ЧМТ оцінювали в дозі 2 мг/кг внутрішньовенно з інтервалом 2 рази на день протягом восьми діб. Як лікарський засіб для контрольної групи застосовували 0,9% NаСl в дозі 2 мл/кг, а препарат порівняння — амантадину сульфат — у дозі 5 мг/кг. Для визначення ефективності досліджуваних препаратів використовували рівень TNF-α. Результати. Порівняльний аналіз ефективності адемолу та амантадину сульфату на восьму добу спостереження показав, що в групі тварин, яким застосовували адемол, уміст TNF-α в тканинах мозку виявився меншим на 57,3 % (р

Aim. The purpose of the research, presented in this paper, is to develop (as the first one in Ukraine) hull-less barley breeding material with ultra-low gluten, combining three hordein-deficient mutations, derived from Risø56, Risø1508, and R118, with black grain color as an indication of bioactive pigments content, enhancing the functional status of grain as a food product. Methods. We used electrophoretic analysis of proteins in polyacrylamide gel, DNA isolation by the CTAB method, polymerase chain reaction with DNA-markers, restriction analysis and electrophoretic separa tion of DNA in agarose gel. Results. The article presents the results of the first stage of combining target hordeindefi cient mutations by binary crosses. The F2/3 and F3/4 populations were derived from binary crosses of Risø56 × Risø1508 (reciprocal Risø1508 × Risø56) and R118 × hull-less barley Achilles. The new PCR protocol was optimized. Markers B1hor, 3a5F and Dhor-m were selected to identify mutations in B, C and D hordeins. Conclusions. Several barley genotypes with one or two target hordein-deficient mutations and black grain color were isolated. The genotypes obtained will be used in a further backcrosses program, aimed at developing of a black hull-less barley variety with ultra-low gluten content.

At the beginning of the first wave of the COVID-19 pandemic, a network of outpatient CT centers (OCTC) for lung pathology diagnostics in patients with suspected viral pneumonia with the round-the-clock operation was formed in Moscow. The introduction of the CT 0-4 scale allowed for effective routing. To prevent the spread of infection among patients and staff, OCTC zoning was introduced, dividing into red, buffer, and green zones. As part of the mobilization of the Radiology Service, the Moscow Reference Center was established, aimed at quality control, remote expert consultations, and organizational and methodological support. Several online courses and training webinars have been developed. Artificial Intelligence services were connected to recognize the signs of COVID-19 and assess the severity. The developed strategy of the Moscow Radiology Service ensured readiness for the high burden on the city health care system and minimized losses among medical personnel. The experts significantly contributed to effective infection control through accessible, timely, and high-quality diagnostics and routing.

SARS-CoV-2, like other coronaviruses, builds a membrane-bound replication organelle (RO) to enable RNA replication(1). The SARS-CoV-2 RO is composed of double membrane vesicles (DMVs) tethered to the endoplasmic reticulum (ER) by thin membrane connectors(2), but the viral proteins and the host factors involved are currently unknown. Here we identify the viral non-structural proteins (NSPs) that generate the SARS-CoV-2 RO. NSP3 and NSP4 generate the DMVs while NSP6, through oligomerization and an amphipathic helix, zippers ER membranes and establishes the connectors. The NSP6ΔSGF mutant, which arose independently in the α, β, γ, η, ι and λ variants of SARS-CoV-2, behaves as a gain-of-function mutant with a higher ER-zippering activity. We identified three main roles for NSP6: to act as a filter in RO-ER communication allowing lipid flow but restricting access of ER luminal proteins to the DMVs, to position and organize DMV clusters, and to mediate contact with lipid droplets (LDs) via the LD-tethering complex DFCP1-Rab18. NSP6 thus acts as an organizer of DMV clusters and can provide a selective track to refurbish them with LD-derived lipids. Importantly, both properly formed NSP6 connectors and LDs are required for SARS-CoV-2 replication. Our findings, uncovering the biological activity of NSP6 of SARS-CoV-2 and of other coronaviruses, have the potential to fuel the search for broad antiviral agents.

Rare genetic diseases preponderantly affect the nervous system causing neurodegeneration to neurodevelopmental disorders. This is the case for both Menkes and Wilson disease, arising from mutations in ATP7A and ATP7B, respectively. The ATP7A and ATP7B proteins localize to the Golgi and regulate copper homeostasis. We demonstrate genetic and biochemical interactions between ATP7 paralogs with the conserved oligomeric Golgi (COG) complex, a Golgi apparatus vesicular tether. Disruption ofDrosophilacopper homeostasis by ATP7 tissue-specific transgenic expression caused alterations in epidermis, aminergic, sensory, and motor neurons. Prominent among neuronal phenotypes was a decreased mitochondrial content at synapses, a phenotype that paralleled with alterations of synaptic morphology, transmission, and plasticity. These neuronal and synaptic phenotypes caused by transgenic expression of ATP7 were rescued by downregulation of COG complex subunits. We conclude that the integrity of Golgi-dependent copper homeostasis mechanisms, requiring ATP7 and COG, are necessary to maintain mitochondria functional integrity and localization to synapses.SIGNIFICANCE STATEMENTMenkes and Wilson disease affect copper homeostasis and characteristically afflict the nervous system. However, their molecular neuropathology mechanisms remain mostly unexplored. We demonstrate that copper homeostasis in neurons is maintained by two factors that localize to the Golgi apparatus, ATP7 and the conserved oligomeric Golgi (COG) complex. Disruption of these mechanisms affect mitochondrial function and localization to synapses as well as neurotransmission and synaptic plasticity. These findings suggest communication between the Golgi apparatus and mitochondria through homeostatically controlled cellular copper levels and copper-dependent enzymatic activities in both organelles.

The article deals with the problem of determining the number of antiaircraft missile systems of various types in grouping of Air Defense troops for the purpose of providing the required effectiveness of repelling the enemy air strikes on the objects and troops. The methodology of justification of ratio of different types of antiaircraft missile systems in the grouping of Air Defense troops using Lagrange’s method of undetermined multipliers has been developed. This technique allows justifying a set of types of antiaircraft missile systems which will provide maximum effectiveness of the employment of grouping of Air Defense troops. This approach can also be used to justify the composition of mixed military formations of Air Defense.

We presented our results on prebiotic containing mannan oligosaccharides (MOS) effectiveness as an immune response modifier in young pigs during their fattening. We found that MOS content at a dose of 0.06% from mixed feed contributed to increase in pig average daily growth by 7.5% and reduced the feed costs on growth gain by 6.3%. We observed that the animal productivity, feed costs per 1 kg of growth gain, slaughter weight, slaughter yield, and pig carcass weight were higher after introduction of prebiotics to mixed feed. We suggested the usage of the prebiotic with mannan oligosaccharides as immune response modifier for young pigs diet during the fattening increase the nutrient contents in slaughter products (meat, lard, and liver).

У статті викладено сучасні дані щодо лікування периімплантиту, що ставить під загрозу результат реставрації з опорою на імплантати. Тому вивчення різноманітних методів лікування периімплантиту є актуальною медико-соціальною проблемою сучасного суспільства. Мета дослідження – на основі аналізу даних літератури визначити найбільш значущі способи корекції периімплантиту та провести їх систематизацію. Матеріали і методи. У дослідженні було використано методи структурно-логічного, бібліосемантичного та аналітичного аналізів літературних джерел. Результати досліджень та їх обговорення. У статті проаналізовано та опрацьовано джерела науково-медичної інформації, що стосуються лікування периімплантиту. Висновки. Способи корекції периімплантиту поділяються на нехірургічні та власне хірургічні. Перед хірургічним потрібно провести нехірургічне лікування, що базується в основному на проведенні періодичних курсів професійної гігієни і використанні місцевої антибактеріальної терапії засобами, що містять хлоргексидин або антибіотики. Перспективними методами корекції периімплантиту є використання лазера та піскоструменевого оброблення.

The indicators of pro- and antioxidant systems in sperm and sperm plasma of breeding boars of Large White breed and SS23 synthetic line were studied. Measurements of antioxidant enzyme activity, determination of lipid peroxidation (LPO) product content, and antioxidant factor were performed. Lipid peroxidation in the semen of healthy breeding boars was characterized by a stable level of activity, which is necessary to ensure normal reproductive functions. Additionally, there was a high content of low molecular weight thiols and proteins. The concentration of SH-groups in spermatozoa was higher (P≤0.05) compared to sperm plasma. The number of total, protein, and free SH-groups in the semen of boars of the synthetic line was higher (P0.05) in relation to animals of the Large White breed. Low catalase (CAT) activity in the sperm was compensated by glutathione peroxidase (GPX). The content of ceruloplasmin (CP) in the sperm of boars was almost twice as high as that of sperm plasma. In spermatozoa, high content of reduced glutathione (GTH) was recorded, which was more than 3 times higher than in the seminal fluid. The main antioxidants of spermatozoa were superoxide dismutase (SOD), CP, SH-groups of proteins, and reduced content of GTH. We revealed that CAT is a key enzyme that neutralizes excess hydrogen peroxide in boar semen. In contrast, in sperm, hydrogen peroxide was inactivated mainly by GPX. Further research on the mechanisms of action of reactive oxygen species on boar semen will help to develop effective methods for sperm storage and successful fertilization of oocytes.

ATP7B is a hepato-specific Golgi-located ATPase, which plays a key role in the regulation of copper (Cu) homeostasis and signaling. In response to elevated Cu levels, ATP7B traffics from the Golgi to endo-lysosomal structures, where it sequesters excess copper and further promotes its excretion to the bile at the apical surface of hepatocytes. In addition to liver, high ATP7B expression has been reported in tumors with elevated resistance to platinum (Pt)-based chemotherapy. Chemoresistance to Pt drugs represents the current major obstacle for the treatment of large cohorts of cancer patients. Although the mechanisms underlying Pt-tolerance are still ambiguous, accumulating evidence suggests that lysosomal sequestration of Pt drugs by ion transporters (including ATP7B) might significantly contribute to drug resistance development. In this context, signaling mechanisms regulating the expression of transporters such as ATP7B are of great importance. Considering this notion, we investigated whether ATP7B expression in Pt-resistant cells might be driven by transcription factor EB (TFEB), a master regulator of lysosomal gene transcription. Using resistant ovarian cancer IGROV-CP20 cells, we found that TFEB directly binds to the predicted coordinated lysosomal expression and regulation (CLEAR) sites in the proximal promoter and first intron region of ATP7B upon Pt exposure. This binding accelerates transcription of luciferase reporters containing ATP7B CLEAR regions, while suppression of TFEB inhibits ATP7B expression and stimulates cisplatin toxicity in resistant cells. Thus, these data have uncovered a Pt-dependent transcriptional mechanism that contributes to cancer chemoresistance and might be further explored for therapeutic purposes.

Copper is an essential nutrient whose redox properties make it both beneficial and toxic to the cell. Recent progress in studying transition metal signalling has forged new links between researchers of different disciplines that can help translate basic research in the chemistry and biology of copper into clinical therapies and diagnostics to exploit copper-dependent disease vulnerabilities. This concept is particularly relevant in cancer, as tumour growth and metastasis have a heightened requirement for this metal nutrient. Indeed, the traditional view of copper as solely an active site metabolic cofactor has been challenged by emerging evidence that copper is also a dynamic signalling metal and metalloallosteric regulator, such as for copper-dependent phosphodiesterase 3B (PDE3B) in lipolysis, mitogen-activated protein kinase kinase 1 (MEK1) and MEK2 in cell growth and proliferation and the kinases ULK1 and ULK2 in autophagy. In this Perspective, we summarize our current understanding of the connection between copper and cancer and explore how challenges in the field could be addressed by using the framework of cuproplasia, which is defined as regulated copper-dependent cell proliferation and is a representative example of a broad range of metalloplasias. Cuproplasia is linked to a diverse array of cellular processes, including mitochondrial respiration, antioxidant defence, redox signalling, kinase signalling, autophagy and protein quality control. Identifying and characterizing new modes of copper-dependent signalling offers translational opportunities that leverage disease vulnerabilities to this metal nutrient.

The work has been performed without the financial support of any grant or a scientific project. The authors express their gratitude to reviewers for relevant comments and recommendations on improving the article quality.

Aims Arrhythmogenic cardiomyopathy (AC) is one of the most common inherited cardiomyopathies, characterized by progressive fibro-fatty replacement in the myocardium. Clinically, AC manifests itself with ventricular arrhythmias, syncope, and sudden death and shows wide inter- and intra-familial variability. Among the causative genes identified so far, those encoding for the desmosomal proteins plakophilin-2 (PKP2), desmoplakin (DSP), and desmoglein-2 (DSG2) are the most commonly mutated. So far, little is known about the molecular mechanism(s) behind such a varied spectrum of phenotypes, although it has been shown that the causative mutations not only lead to structural abnormalities but also affect the miRNA profiling of cardiac tissue. Here, we aimed at studying the pathogenic effects of a nonsense mutation of the desmoglein-2 gene, both at the structural level and in terms of miRNA expression pattern.Methods and results We generated transgenic mice with cardiomyocyte-specific overexpression of a FLAG-tagged human desmoglein-2 harbouring the Q558* nonsense mutation found in an AC patient. The hearts of these mice showed signs of fibrosis, decrease in desmosomal size and number, and reduction of the Wnt/beta-catenin signalling. Genome-wide RNA-Seq performed in Tg-hQ hearts and non-transgenic hearts revealed that 24 miRNAs were dysregulated in transgenic animals. Further bioinformatic analyses for selected miRNAs suggested that miR-217-5p, miR-499-5p, and miR-708-5p might be involved in the pathogenesis of the disease.Conclusion Down-regulation of the canonical Wnt/beta-catenin signalling might be considered a common key event in the AC pathogenesis. We identified the miRNA signature in AC hearts, with miR-708-5p and miR-217-5p being the most up-regulated and miR-499-5p the most down-regulated miRNAs. All of them were predicted to be involved in the regulation of the Wnt/beta-catenin pathway and might reveal the potential pathophysiology mechanisms of AC, as well as be useful as therapeutic targets for the disease.

Background & Aims In Wilson disease, ATP7B mutations impair copper excretion into bile. Hepatic copper accumulation may induce mild to moderate chronic liver damage or even acute liver failure. Etiologic factors for this heterogeneous phenotype remain enigmatic. Liver steatosis is a frequent finding in Wilson disease patients, suggesting that impaired copper homeostasis is linked with liver steatosis. Hepatic mitochondrial function is affected negatively both by copper overload and steatosis. Therefore, we addressed the question of whether a steatosis-promoting high-calorie diet aggravates liver damage in Wilson disease via amplified mitochondrial damage. Methods Control Atp7b+/- and Wilson disease Atp7b-/- rats were fed either a high-calorie diet (HCD) or a normal diet. Copper chelation using the high-affinity peptide methanobactin was used in HCD-fed Atp7b-/- rats to test for therapeutic reversal of mitochondrial copper damage. Results In comparison with a normal diet, HCD feeding of Atp7b-/- rats resulted in a markedly earlier onset of clinically apparent hepatic injury. Strongly increased mitochondrial copper accumulation was observed in HCD-fed Atp7b-/- rats, correlating with severe liver injury. Mitochondria presented with massive structural damage, increased H2O2 emergence, and dysfunctional adenosine triphosphate production. Hepatocellular injury presumably was augmented as a result of oxidative stress. Reduction of mitochondrial copper by methanobactin significantly reduced mitochondrial impairment and ameliorated liver damage. Conclusions A high-calorie diet severely aggravates hepatic mitochondrial and hepatocellular damage in Wilson disease rats, causing an earlier onset of the disease and enhanced disease progression., Graphical abstract

The objective of this study was to perform a comprehensive evaluation of major indices of pain syndrome in patients with mandibular fractures accompanied by damage of inferior alveolar nerve using conventional therapeutic regimen supplemented by the administration of drug product Nucleo CMP Forte. Operative and postoperative treatment of 50 patients with angular fractures of the mandible, accompanied by clinical manifestations of inferior alveolar nerve damage, was performed. The severity of pain syndrome and neuropathy symptoms was evaluated using the LANSS pain scale, DN4 questionnaire, the Visual Analogue Scale (VAS) and Neuropathy Total Symptom Scores (NTSS-9). Decrease of pain syndrome was revealed in both groups but with different dynamic pattern. In the treatment group pain syndrome manifestations and neuropathy symptoms decreased quicker than in the comparison group. As LANSS, DN4, VAS and NTSS-9 scales characterize pain syndrome from various perspectives, the results were different but similar tendency was shown. At the beginning of the study LANSS scale indices were nearly identical in both groups, while on the 7th and 14th day they were 1.35 and 2.03 times lower, respectively, in the treatment group compared to the control group. On the first day NTSS-9 scale values did not practically differ in between the studied patients, being somewhat higher in the treatment group. On the 7th and 14th day the values increased 1.24 and 3.82 times, in the treatment group and in the group of comparison, respectively. Thus, the patients in the treatment group showed significantly greater pain relief than those in the comparison group. The analysis of dynamic pattern of complaints as well as the objective findings in angular fractures of the mandible, accompanied by the damage of inferior alveolar nerve, demonstrated that the administration of drug product Nucleo CMP Forte led to a more pronounced improvement of pain syndrome in the course of treatment. Because of the fact that neuropathic pain can develop in orthodontic treatment, as well as when partial and complete removable dentures are used, the administration of drug product Nucleo CMP Forte is warranted in combined therapy of both mandibular fractures followed by the clinical manifestations of inferior alveolar nerve damage, and neuropathic pain management in orthodontics and orthopedic stomatology.

Pompe disease is a metabolic myopathy due to acid alpha‐glucosidase deficiency. In addition to glycogen storage, secondary dysregulation of cellular functions, such as autophagy and oxidative stress, contributes to the disease pathophysiology. We have tested whether oxidative stress impacts on enzyme replacement therapy with recombinant human alpha‐glucosidase (rhGAA), currently the standard of care for Pompe disease patients, and whether correction of oxidative stress may be beneficial for rhGAA therapy. We found elevated oxidative stress levels in tissues from the Pompe disease murine model and in patients’ cells. In cells, stress levels inversely correlated with the ability of rhGAA to correct the enzymatic deficiency. Antioxidants (N‐acetylcysteine, idebenone, resveratrol, edaravone) improved alpha‐glucosidase activity in rhGAA‐treated cells, enhanced enzyme processing, and improved mannose‐6‐phosphate receptor localization. When co‐administered with rhGAA, antioxidants improved alpha‐glucosidase activity in tissues from the Pompe disease mouse model. These results indicate that oxidative stress impacts on the efficacy of enzyme replacement therapy in Pompe disease and that manipulation of secondary abnormalities may represent a strategy to improve the efficacy of therapies for this disorder., Enzyme replacement therapy (ERT) with recombinant human alpha‐glucosidase (rhGAA) is currently the standard of care for the treatment of Pompe disease. However, this approach shows important limitations. We have tested whether modulation of oxidative stress may improve the efficacy of ERT.

Trigonal tellurium, a small-gap semiconductor with pronounced magneto-electric and magneto-optical responses, is among the simplest realizations of a chiral crystal. We have studied by spin- and angle-resolved photoelectron spectroscopy its unconventional electronic structure and unique spin texture. We identify Kramers-Weyl, composite, and accordionlike Weyl fermions, so far only predicted by theory, and show that the spin polarization is parallel to the wave vector along the lines in k space connecting high-symmetry points. Our results clarify the symmetries that enforce such spin texture in a chiral crystal, thus bringing new insight in the formation of a spin vectorial field more complex than the previously proposed hedgehog configuration. Our findings thus pave the way to a classification scheme for these exotic spin textures and their search in chiral crystals.

The use of computed tomography (CT) for the diagnostics of COVID-19 in the Russian Federation led to significant changes in the structure of X-ray diagnostics and levels of medical exposure of the patients. This study was aimed at the preliminary operative assessment of changes in the structure and collective dose from CT examinations in several representative hospitals, regions and on the level of the Russian Federation. The results of the study indicate that during the transformation of hospitals from general medical practice into dedicated COVID-19 facilities, the number of CT examinations increased up to 30%; the collective dose from CT exams increased up to a factor of 1.5. During a partial transformation of a medical facility into the hospital with separate COVID-19 departments, the increase in the number of CT examinations in the facility was more significant (up to a factor of 2 or more). These numbers correspond to 1.5 - 2.5 chest CT examinations (from 1 to 6) per patient admitted to hospital with COVID-19 diagnosis; and 1.2 chest CT examinations per patient in outpatient facilities, including a mandatory CT scan for the staging of COVID-19. The collective dose from CT examinations in the Russian Federation for March-June period of 2020 increased by the factor of 2 (from 16k man-Sv to 32k man-Sv); the collective dose of COVID-19 patients was about 12k man-Sv. For a more detailed and reliable assessment of the dynamics of changes in the structure of diagnostic radiology and levels of radiation exposure of patients in the Russian Federation, data collection in the regions of the Russian Federation and individual medical facilities will continue.

H1069Q substitution represents the most frequent mutation of the copper transporter ATP7B causing Wilson disease in Caucasian population. ATP7B localizes to the Golgi complex in hepatocytes but moves in response to copper overload to the endo-lysosomal compartment to support copper excretion via bile canaliculi. In heterologous or hepatoma-derived cell lines, overexpressed ATP7B-H1069Q is strongly retained in the ER and fails to move to the post-Golgi sites, resulting in toxic copper accumulation. However, this pathogenic mechanism has never been tested in patients' hepatocytes, while animal models recapitulating this form of WD are still lacking. To reach this goal, we have reprogrammed skin fibroblasts of homozygous ATP7B-H1069Q patients into induced pluripotent stem cells and differentiated them into hepatocyte-like cells. Surprisingly, in HLCs we found one third of ATP7B-H1069Q localized in the Golgi complex and able to move to the endo-lysosomal compartment upon copper stimulation. However, despite normal mRNA levels, the expression of the mutant protein was only 20% compared to the control because of endoplasmic reticulum-associated degradation. These results pinpoint rapid degradation as the major cause for loss of ATP7B function in H1069Q patients, and thus as the primary target for designing therapeutic strategies to rescue ATP7B-H1069Q function.