Counteracting Mechanism Research Articles

Lymphocytic Thyroiditis Transcriptomic Profiles Support the Role of Checkpoint Pathways and B Cells in Pathogenesis.

Background: Autoimmune thyroid diseases are the most common types of autoimmune diseases, but their physiopathology is still relatively unexplored. Genotype-tissue expression (GTEx) is a publicly available repository containing RNAseq data, including profiles from thyroid. Approximately 14.8% of these glands were affected by focal lymphocytic thyroiditis and 6.3% were annotated as Hashimoto. We interrogated these data to improve the characterization of infiltrating cells and to identify new molecular pathways active in autoimmune thyroiditis. Materials and Methods: Histological GTEx images of 336 thyroid samples were classified into three categories, that is, non-infiltrated thyroid, small focal infiltrated thyroid, and extensive lymphoid infiltrated thyroid. Differentially expressed genes among these categories were identified and subjected to in silico pathway enrichment analysis accordingly. CIBERSORTx deconvolution was used to characterize infiltrating cells. Results: As expected, most of the transcriptional changes were dependent on tissue infiltration. Upregulated genes in tissues include-in addition to lineage-specific B and T cell genes-a broad representation of inhibitory immune checkpoint receptors expressed by B and T lymphocytes. CIBERSORTx analysis identified 22 types of infiltrating cells showed that T cells predominate 3:1 over B cells in glands with small infiltrates, only by 1.7:1 in those with large infiltrates. Follicular helper and memory CD4 T cells were significantly more abundant in glands with large infiltrates (p < 0.0001), but the most prominent finding in these glands was an almost sixfold increase in the number of naive B cells (p < 0.0001). A predominance of M2 macrophages over M1 and M0 macrophages was observed in the three gland categories (p < 0.001). Conclusions: Analysis of transcriptomic RNA-seq profiles constitutes a rich source of information for the analysis of autoimmune tissues. High-resolution transcriptomic data analysis of thyroid glands indicates the following: (a) in all infiltrated glands, active autoimmune response coexists with suppressor counteracting mechanisms involving several inhibitory checkpoint receptor pairs, (b) glands with small infiltrates contain an unexpected relatively high proportion of B lymphocytes, and (c) in highly infiltrated glands, there is a distinct transcriptomic signature of active tertiary lymphoid organs. These results support the concept that the autoimmune response is amplified in the thyroid tissue.

Problems of Legal Regulation of Combating Torture in Ukraine

Abstract The relevance of this study is due to the lack of an effective mechanism to combat torture in Ukraine and an insufficiently effective system of prevention and protection against torture, which creates an atmosphere of impunity and leads to the spread of this phenomenon in Ukraine. The purpose of the article is to explore the problematic aspects of legal counteraction to torture in Ukraine and to suggest ways to improve the mechanism of legal counteraction to torture in Ukraine in the context of international standards. Thus, first of all, the article reveals the composition of the crime of torture and the specifics of responsibility for it in Ukraine. Then the paper characterizes the mechanism for ensuring legal counteraction to torture in Ukraine. The article also analyzes the main problems of legal counteraction to torture in Ukraine suggests ways to improve certain problems of legal counteraction to torture in Ukraine in the context of international standards.

Transcriptome analysis of blastoderms exposed to prolonged egg storage and short periods of incubation during egg storage

BackgroundCool temperature egg storage prior to incubation is a common practice in the broiler industry; however, prolonged egg storage causes increased embryonic mortality and decreased hatchability and growth in surviving chicks. Exposing eggs to short periods of incubation during egg storage (SPIDES) reduces the adverse consequences of prolonged storage. SPIDES increases blastodermal cell viability by reducing apoptosis, though the counteracting mechanisms are unclear. To define the impact of prolonged storage and SPIDES, transcriptome analysis compared gene expression from blastoderms isolated from eggs exposed to the following treatments: control (CR, stored at 17 °C for 4 days), prolonged storage (NSR, stored at 17 °C for 21 days), SPIDES (SR, stored at 17 °C for 21 days with SPIDES), and incubated control (C2, stored at 17 °C for 4 days followed by incubation to HH (Hamburger–Hamilton) stage 2, used as the ideal standard development) (n = 3/group). Data analysis was performed using the CLC Genomics Workbench platform. Functional annotation was performed using DAVID and QIAGEN Ingenuity Pathway Analysis.ResultsIn total, 4726 DEGs (differentially expressed genes) were identified across all experimental group comparisons (q < 0.05, FPKM> 20, |fold change| > 1.5). DEGs common across experimental comparisons were involved in cellular homeostasis and cytoskeletal protein binding. The NSR group exhibited activation of ubiquitination, apoptotic, and cell senescence processes. The SR group showed activation of cell viability, division, and metabolic processes. Through comparison analysis, cellular respiration, tRNA charging, cell cycle control, and HMBG1 signaling pathways were significantly impacted by treatment and potential regulatory roles for ribosomal protein L23a (RPL23A) and MYC proto-oncogene, BHLH transcription factor (MYC) were identified.ConclusionsProlonged egg storage (NSR) resulted in enriched cell stress and death pathways; while SPIDES (SR) resulted in enriched basic cell and anti-apoptotic pathways. New insights into DNA repair mechanisms, RNA processing, shifts in metabolism, and chromatin dynamics in relation to egg storage treatment were obtained through this study. Although egg storage protocols have been examined through targeted gene expression approaches, this study provided a global view of the extensive molecular networks affected by prolonged storage and SPIDES and helped to identify potential upstream regulators for future experiments to optimize egg storage parameters.

SOME ISSUES REGARDING ORGANIZATION OF THE INTERDEPARTMENTAL INTERACTION OF NATIONAL POLICE BODIES WITH OTHER LAW ENFORCEMENT BODIES (INTEGRATED ORGANIZATION OF POLICEACTIVITIES)

The article considers the problems of the main directions of interaction of the national police with other public administration bodies in the field of law enforcement, investigates theoretical and legal issues of police interaction with law enforcement agencies in the field of protection of human and civil rights and freedoms, and regulatory legal regulation. In particular, the legal essence of interaction is determined, which includes the concept of its individual elements, as well as the signs and principles of its implementation, a distinction is made between the categories of “interaction”, “coordination” and “cooperation”. On this basis and on the basis of the analysis of normative legal acts of different levels the forms and directions of interaction are defined, the lack of attention of joint coordination and the organization of interaction is stated that does not provide coordinated work of law enforcement agencies and negatively affects the overall results of their work, identified a number of factors that slow down (make impossible) the interaction between law enforcement agencies, emphasized the mechanisms of prevention and counteraction, conducted an in-depth comparative analysis of different approaches to the category of «interaction», provided an author’s definition of interaction and interaction between law enforcement and the national police.

Субъективные причины злоупотребления правом: нравственно-правовой аспект

The article is devoted to the analysis of the problem of the influence of subjective reasons on the occurrence of cases of abuse of right. The study aims to substantiate the role of moral and legal aspect of the subjective causes of abuse of rights in the formation of the purpose of the rights that do not meet the purpose of law as a social regulator. The use of formal-logic method allowed us to consider in unity the moral and legal aspects of abuse of rights, the method of materialistic dialectics allowed us to substantiate the conclusions of the study. We have considered deformation of legal consciousness, low level of legal culture, legal egoism and legal egocentrism as subjective reasons of malicious exercise of law. The value of moral categories in forming of aims of law abuse is analysed. It was established that deformation of moral-legal values has a direct impact on the implementation of the rights granted to the subjects. The article substantiates the influence of transformation of attitude of individuals to the law and morality on the occurrence of cases of right abuse. We prove the impossibility to consider this legal phenomenon as a type of deformation of legal consciousness. The notion of legal egoism and legal egocentrism as the main subjective reasons of malicious exercise of law was formed. We have made a conclusion about the necessity of further research of the factors influencing changes of moral-legal sphere of legal subjects in order to create the effective mechanism of counteraction and prevention of abuse of law. The data obtained can be used in future studies dedicated to the study of the problem of abuse of law, identification of the causes and conditions of the malicious exercise of law, the formation of mechanism of counteraction and prevention of this negative legal phenomenon.

Models based on "estimation bias" as a tool for predicting potential threats

In statistics, there is a phenomenon called "estimation bias". It is determined by the fact that with the spontaneous formation of the studied samples in social research, a kind of "shift" occurs, determined by the motivation of respondents. The analysis shows that a similar phenomenon occurs in many areas of evaluation related to a person: writing reviews about products and services, conducting surveys, forming applications. This principle can manifest itself in the formation of public opinion on socially significant issues: during elections, referendums, and the like. Moreover, knowledge of the principle of "displacement" can be used to organize a deliberate "shift" of the results of socially significant surveys. Examples of such use are the technologies of "color" revolutions carried out by relatively small groups of people or the well–known method of so-called "smart voting". Using general scientific methods of analysis and synthesis, the article shows possible approaches to the formation of such "shifts", analyzes the possible consequences of the implementation of such technologies and formulates proposals to counteract them. It is concluded that the purposeful use of "bias" assessment technologies can lead to conflicts of interests between different groups of society and the authorities, but it could not be corrected until now due to the lack of appropriate counteraction mechanisms. The development of mechanisms for assessing the consequences of the "shift" and countering it, theoretically, can provide counteraction to the use of external influences to destabilize the state in the case of intentional use of the "shift". In case of accidental formation of a "bias", forecasting methods will ensure the detection of an error. Conclusions are drawn that the proposed methodology for assessing the "bias" is not just a theory, its implementation will have a practical effect, which is to increase the stability of the system of state and municipal management.

ECONOMIC AND LEGAL MECHANISM FOR COMBATING LEGALIZATION (LAUNDERING) OF INCOME RESULTING FROM TAX EVASION IN THE CONTEXT OF DEOFFSHORIZATION OF UKRAINE’S ECONOMY

Abstract. Growing trends in the shadowing of the international and national economy contribute to the strengthening of legalization of income resulting from tax evasion, using offshore zones, which have favorable fiscal and monetary and financial regimes, with a high degree of protection of banking and trade secrecy, as well as loyalty to institutional regulation. In recent years, the problem of legalization (laundering) of income from tax evasion in offshore zones has become more acute, caused by the violation of Ukraine’s national interests due to the reduction of tax revenues to the state budget and the outflow of capital outside the country. The offshoring of the national economy has reached alarming proportions as the country, in a prolonged financial and economic crisis, chronic underfunding of sectors of the national economy and acute shortage of financial resources, invests in highly developed countries. Given this situation, the problem of studying the mechanism of counteraction to legalization (laundering) of income received as a result of tax evasion in offshore zones becomes especially relevant. The article identifies the features and prerequisites for the functioning of offshore zones, outlines the main problems of effective counteraction to legalization (laundering) of income received as a result of tax evasion in offshore zones. The research of the basic schemes and methods of legalization (laundering) of the incomes received as a result of tax evasion with use of offshore zones is carried out; the economic and legal analysis of normative and legislative maintenance in the field of counteraction to legalization (laundering) of the incomes received as a result of tax evasion, in offshore zones is performed; the dynamics of the number of criminal offenses in the field of tax evasion with the use of offshore zones is analyzed. Measures of the system of counteraction to legalization (laundering) of incomes received as a result of tax evasion through offshore zones are systematized and improvement of the economic and legal mechanism of counteraction to legalization (laundering) of the incomes received as a result of tax evasion through offshore zones is offered. Keywords: legalization (laundering) of income, tax evasion, economic and legal mechanism, offshore zones. JEL Classification H26, O17 Formulas: 0; fig.: 4; tabl.: 0; bibl.: 13.

Theoretical and applied problems of counteracting organized groups and criminal organizations that are formed on an ethnic basis in Asia, Africa and Australia

Formation by the Ukrainian state of a multi-vector mechanism of counteraction to organized groups and criminal organizations formed on an ethnic basis is impossible without understanding the essence of this problem, relevant statutory concepts and classification and separation of features of organized ethnic crime, which are important for law enforcement and the main effective factor in such activities is to guarantee the security of citizens and the integrity of the state from criminal encroachments of organized groups and criminal organizations that are formed on an ethnic basis. It is stated that today among domestic scientists there are no comprehensive studies of organized groups and criminal organizations, which are formed on an ethnic basis. At the same time, such comprehensive studies are absent in European and American. researchers. Although the latter have positive isolated changes in this area. The main attention and efforts of researchers are attracted to large-scale organized ethnic groups. Based on a comparative legal study of foreign experience in Asia, Africa and Australia in combating crimes committed by organized groups and criminal organizations formed on an ethnic basis, the possibilities of introducing positive foreign experience in the work of law enforcement agencies of Ukraine have been identified. It is noted that the importance of our scientific intelligence, first of all, is that in practice, law enforcement agencies engaged in combating organized groups and criminal organizations that are formed on an ethnic basis, had the opportunity to have an idea of ​​this negative phenomenon. The article also emphasizes the peculiarities of collecting, analyzing, accumulating and storing information exchange for its convenient and effective use by law enforcement agencies of different countries in detecting, documenting and investigating crimes committed by organized groups and criminal organizations formed on an ethnic basis.

Отзыв официального оппонента о диссертации З. М. Бешуковой «Механизм уголовно-правового противодействия экстремистской деятельности: содержание, структура, основные направления оптими- зации», представленной на соискание ученой степени доктора юридических наук по специальности 12.00.08

Objective: to conduct a comprehensive analysis of the doctoral thesis by Z. M. Beshukova on “Mechanism of criminal-legal counteraction to extremist activity: content, structure, main directions of optimization”, defended in 2021 in the Dissertation Council D 212.320.04 at Chechen State University.Methods: the dialectical method of cognition was used, which, taking into account the topic and content of the thesis, determined the choice of the following research methods: analysis, synthesis, comparative-legal method, etc.Results: the author’s concept is studied, aimed at increasing the level of criminal-legal counteraction to extremist activities. The relevance of the direction taken for the study is confirmed. The main directions of criminal policy optimization in the studied area are highlighted, including by demonstration of their content and structure. The main provisions submitted for defense are supported, which constitute the author’s research concept. The reviewer’s opinions on the thesis are presented, concerning the use of positive foreign experience in counteracting extremism, the proposed options for the terrorist and extremist crimes qualification, as well as the proposed legal conditions governing the grounds for exemption from criminal liability for persons who participated in the activities of an extremist organized group or extremist community. A critical evaluation was carried out for the main provisions of the thesis, for example, the absence of the author’s concept of extremist activity; the definition of goods and values in relation to which the goals are achieved and the functions of the criminal-legal counteraction to extremism are implemented; the author’s classification of terrorist crimes; the proposed version of Article 2821 of the Criminal Code of the Russian Federation “Creation of an extremist organized group, extremist community or participation in it”.Scientific novelty: the author evaluates the thesis by Z. M. Beshukova, submitted for the degree of Doctor of Law in the major “12.00.08 - Criminal Law and Criminology; Criminal Executive Law” on “Mechanism of criminal-legal counteraction to extremist activity: content, structure, main directions of optimization”, identifies its scientific achievements, defines the provisions that allow adjusting the criminal policy in the sphere of extremism counteraction.Practical significance: the review allows using the obtained results in all elements of legal technique focused on countering extremist activities.

Variations in Salivary Stress Biomarkers and Their Relationship with Anxiety, Self-Efficacy and Sleeping Quality in Emergency Health Care Professionals.

Hospital healthcare workers of emergency departments (EDs) face a variety of occupational stressors on a daily basis. We have recently published that emergency professionals display increased salivary levels of α-amylase and dehydroepiandrosterone during the working day. The pattern of these markers may suggest a counteracting mechanism of dehydroepiandrosterone against the stress reflected by amylase increases. In order to verify this hypothesis, we have analysed different psychological aspects in the same group of healthcare professionals through different tests related to behaviours resulting from stress. These include the state-trait anxiety inventory, the self-efficacy test and the sleeping quality questionnaire. The tests were provided at the beginning of the working day and collected at the end. STAI scores (trait and state) were indicative of no anxiety. Self-efficacy scores were considered optimal, as well as those from the sleeping quality questionnaire. This is supported by the modest correlation between STAI scores and salivary levels of α-amylase and dehydroepiandrosterone. In conclusion, the emergency professionals of the studied hospitals seem to have adequate work management. Altogether it means that the stress generated during work performance is controlled, allowing a correct adaptation to the demanding situations undergone in emergency departments.

To the issue of improving the mechanism of drug criminality counteraction

The article deals with the problematic issues of improving the functioning of the mechanism of combating drug crime and on this basis formulated recommendations aimed at improving the legal basis and practice of crimino-logical impact on drug crime. It is concluded that the search for directions of rationalization of the mechanism of combating drug crime can and should be conducted by revealing the degree of influence of the whole management mechanism, its individual elements on the objects of criminological influence in the sphere of combating drug crime, in particular, on the state of law, ensuring public safety, combating crime. The first direction of improvement of the mechanism of combating drug crime is the necessity of a scientifically grounded approach in determining the objective activity for combating drug crime on the basis of objective social needs. The formation of the subject competence of the subjects of combating drug crime must be laid down in three important conditions: first, the prin-ciple of separation of powers, according to which law enforcement agencies are assigned to the executive branch of power; secondly, the protection of only the part of the public relations which the offender encroaches upon by committing a criminal offense can be attributed to the substantive activity of law enforcement agencies; third, law enforcement agencies may be subject only to those relationships that objectively require coercive measures. Another important direction of improving the mechanism of combating drug crime is to bring the crime management system in line with the requirements of scientifically sound principles. These are the principles of balance of rights and re-sponsibilities, personal responsibility of the official for the actions or decisions taken, differentiation of competences of different bodies, divisions and officials, fixing them in the normative legal acts, conformity of the position, deter-mining the main executive level, proportional application coercive measures, etc. It is emphasized that the structural and organizational improvement of the mechanism of combating drug crime necessitates the need to determine the structure - the leader of state policy in this field, as well as the subjects of direct counteraction to drug crime. In view of these circumstances, it is important to create an organizational model of the mechanism for combating drug crime, which would include, first, the enhancement of the status of coordination bodies under the Cabinet of Ministers of Ukraine; secondly, the organizational units in the structure of the executive power of the regional level, which would provide at this level the organization of anti-narcotic activities, especially outside the sphere of law enforcement agencies; third, coordination units providing structurally (by directions): operational-search activities, external intelligence, pre-trial investigation, administrative activities in the field of control over legal drug traffick-ing, providing a single information base on drug trafficking and combating drug crime, other areas counteraction, due to the nature of the complex operational environment.

International Legal Regulation and Supranational Interaction in Counteracting the COVID-19 Pandemic: Challenges and Proposals

The purpose of the article is to study problems of international legal regulation and supranational cooperation in combating the COVID-19 pandemic. The institutional and international legal mechanism of counteraction to the spread of the pandemic is analyzed. The problem moments of realization of provisions of the main international acts in the area of counteraction to the Coronavirus disease by the national governments are marked out. The methodological basis for the article is general and special methods and techniques of scientific knowledge, in particular: formal-logical, Aristotelian method, method of documentary, system-structured method, formal and legal method, forecasting method, method of generalization. The key problems of international legal counteraction to the pandemic spread are as follows: advisory (not obligatory) character of the majority of international legal acts related to the fight against COVID-19; disinterest of the states in timely informing WHO about the outbreaks of infectious diseases; arbitrary interpretation of the international acts by national governments; human rights restrictions on the movement imposed by the states; lack of a clear funding mechanism to build the necessary global and national infrastructure to ensure commitment in accordance with the International Health Regulations.

Yes, but not now! Why some users procrastinate in adopting digital product updates

Users of digital products (such as mobile apps or software) are frequently offered new versions in the form of updates. While updates can deliver benefits, they may also interfere with the ongoing use of digital products. We investigate why digital product users might delay implementing adoption intentions (which we term adoption procrastination) of updates. Three experimental studies show that while users may intend to adopt new versions, they deliberately delay adopting them under certain conditions. Specifically, we identify how perceived changes in the new version can trigger annoyance, leading to adoption procrastination. We further identify anticipated inaction regret as a counteracting mechanism, which reduces adoption procrastination. Our research makes theoretical and empirical contributions to consumer innovation adoption literature. First, we introduce the novel concept of adoption procrastination, expanding previously examined adoption-related decisions. Second, we propose and empirically test cognitive and affective mechanisms determining digital product users’ adoption procrastination.

Антироссийские санкции как предпосылка расширения международного научно-технического сотрудничества с азиатскими странами

The article describes the international scientific and technical cooperation (ISTC) of the Russian Federation with foreign states in the context of the anti-Russian sanctions. The research featured the political and economic anti-Russian sanctions that define the current cooperation in the scientific and technical field. The authors described the phenomenon of sanctions, their main types, reasons, specific features, etc., putting stress on the industrial and selective character, as well as on their indirect influence on Russian ISTC. There are no scientific and technological sanctions per se; however, the current political and economic sanctions keep affecting the ISTC sphere, e.g. inability to purchase and deliver reagents and high-tech equipment, to accept financing from foreign funds, etc. The sanctions manifest themselves as narrow scope of research projects, low academic mobility, etc. The two areas with appropriate mechanisms to counter the sanctions policy are political and legal. For instance, a diversified state policy could be developed to support ISTC. Public scientific diplomacy and an official vector of development might be of great help, in particular, the Asian vector of ISTC development. The authors believe ISTC should take place between the members of the Shanghai Cooperation Organization. The legal counteraction mechanisms include issuing normative legal acts, suspension of international agreements in ISTC, counter-sanctions, and international arbitration.

The principles of providing emergency care for patients with pancreatic necrosis

At the present stage, the treatment of patients with pancreatic necrosis is one of the most urgent surgical tasks. Pancreatic necrosis is a destructive lesion of the pancreas, often leading to the development of multiple organ failure. The pathogenesis is based on a violation of the mechanism of counteraction to proteolytic enzymes produced by the pancreas. Pancreatic necrosis is a formidable complication of pancreatitis, with mortality ranging from 30 to 70 %. Today, in terms of the frequency of occurrence in surgical practice, this pathology ranks second after acute appendicitis. The leading role in the prevention of the development of pancreatic necrosis and the prevention of mortality is taken by early detection, timely hospitalization and the fastest possible start of therapeutic measures. A special place in the treatment of pancreatic necrosis is occupied by measures aimed at rehydration, optimization of hemodynamic parameters, the prescription of vasoactive drugs and prophylactic antibiotics in order to prevent the development of infectious complications.

Theoretical fundamentals of interaction of law enforcement authorities in counteraction of crimes committed by organized groups or criminal organizations formed by an ethnic basis

The analysis of the researched scientific problems on counteraction to crimes, committed by organized groups and criminal organizations, which are formed on an ethnic basis, now necessitates further research of ethnic crime in Ukraine and the world in general. Formation by the Ukrainian state of a multi-vector mechanism of counteraction to organized groups and criminal organizations, formed on an ethnic basis, is impossible without understanding the essence of this problem, relevant legal concepts and classification and identification of features of organized ethnic crime that are important for law enforcement and the state. The main effective factor in such activities is to guarantee the security of citizens and the integrity of the state from criminal encroachments of organized groups and criminal organizations that are formed on an ethnic basis. Thus, for the effective interaction of law enforcement agencies in combating crimes, committed by organized groups and criminal organizations that are formed on an ethnic basis, a sound concept of such cooperation is needed, which is currently lacking. Accordingly, in the long run, such a concept needs to be adopted immediately, which will start streamlining law enforcement relations on the exchange and realization of information concerning the activities of both domestic criminal groups and organized criminal groups of foreign nationals or those formed on ethnic grounds. Theoretical principles of law enforcement interaction in combating crimes, committed by organized groups and criminal organizations, which are formed on an ethnic basis by generalizing, analyzing and systematizing the concept of interaction, its forms, methods and types, are analyzed. An author's definition of the concept of interaction among police during counteraction to crimes, committed by organized groups and criminal organizations, formed on ethnic basi, is given

Combined Effects of Exercise and Denosumab Treatment on Local Failure in Post-menopausal Osteoporosis-Insights from Bone Remodelling Simulations Accounting for Mineralisation and Damage.

Denosumab has been shown to increase bone mineral density (BMD) and reduce the fracture risk in patients with post-menopausal osteoporosis (PMO). Increase in BMD is linked with an increase in bone matrix mineralisation due to suppression of bone remodelling. However, denosumab anti-resorptive action also leads to an increase in fatigue microdamage, which may ultimately lead to an increased fracture risk. A novel mechanobiological model of bone remodelling was developed to investigate how these counter-acting mechanisms are affected both by exercise and long-term denosumab treatment. This model incorporates Frost's mechanostat feedback, a bone mineralisation algorithm and an evolution law for microdamage accumulation. Mechanical disuse and microdamage were assumed to stimulate RANKL production, which modulates activation frequency of basic multicellular units in bone remodelling. This mechanical feedback mechanism controls removal of excess bone mass and microdamage. Furthermore, a novel measure of bone local failure due to instantaneous overloading was developed. Numerical simulations indicate that trabecular bone volume fraction and bone matrix damage are determined by the respective bone turnover and homeostatic loading conditions. PMO patients treated with the currently WHO-approved dose of denosumab (60 mg administrated every 6 months) exhibit increased BMD, increased bone ash fraction and damage. In untreated patients, BMD will significantly decrease, as will ash fraction; while damage will increase. The model predicted that, depending on the time elapsed between the onset of PMO and the beginning of treatment, BMD slowly converges to the same steady-state value, while damage is low in patients treated soon after the onset of the disease and high in patients having PMO for a longer period. The simulations show that late treatment PMO patients have a significantly higher risk of local failure compared to patients that are treated soon after the onset of the disease. Furthermore, overloading resulted in an increase of BMD, but also in a faster increase of damage, which may consequently promote the risk of fracture, specially in late treatment scenarios. In case of mechanical disuse, the model predicted reduced BMD gains due to denosumab, while no significant change in damage occurred, thus leading to an increased risk of local failure compared to habitual loading.

METHODOLOGY OF ECONOMIC SECURITY AT THE ENTERPRISE ON BASIS OF APPLICATION THE PROJECT APPROACH IN THE FOCUS OF MODERN CHALLENGES: REGULATORY FRAMEWORK

In modern transformational conditions, economic processes are characterized by the main features of the growth phase and crisis, which is justified by the need to ensure economic security of enterprises. In such conditions, the theoretical basis includes a variety of methodological approaches to the study of this category. On the basis of the conducted researches it is established that the final choice of the enterprise of the corresponding approach to its maintenance depends on a scientific definition of economic safety. Regardless of the approach chosen, each system of economic security has a certain set of elements, such as object, subject, subject and subjects of counteraction, monitoring, analysis and assessment of risks, dangers, challenges and threats, counteraction mechanism. For a methodologically correct solution to the problem of economic security of the enterprise requires a clear understanding of the specifics of each approach to the definition of these elements. The purpose of the article is to substantiate the essential characteristics of economic security enterprises, as well as the formation of the main procedure for assessing the level of economic security with justification of efficiency in modern transformational conditions. A comprehensive study of the substantive characteristics of the project management methodology. The main stages of work on the project based on the PRINCE2 methodology are substantiated. And also the practical mechanism of realization economic safety the enterprise in context of the project approach is investigated.

Hemostatic alterations linked to body fat distribution, fatty liver, and insulin resistance

ObjectiveObesity, in particular visceral obesity, and insulin resistance emerged as major risk factors for severe coronavirus disease 2019 (COVID-19), which is strongly associated with hemostatic alterations. Because obesity and insulin resistance predispose to thrombotic diseases, we investigated the relationship between hemostatic alterations and body fat distribution in participants at risk for type 2 diabetes. SubjectsBody fat distribution (visceral and subcutaneous abdominal adipose tissue) and liver fat content of 150 participants – with impaired glucose tolerance and/or impaired fasting glucose – were determined using magnetic resonance imaging and spectroscopy. Participants underwent precise metabolic characterization and major hemostasis parameters were analyzed. ResultsProcoagulant factors (FII, FVII, FVIII, and FIX) and anticoagulant proteins (antithrombin, protein C, and protein S) were significantly associated with body fat distribution. In patients with fatty liver, fibrinogen (298 mg/dl vs. 264 mg/dl, p = 0.0182), FVII (99% vs. 90%, p = 0.0049), FVIII (114% vs. 90%, p = 0.0098), protein C (124% vs. 111%, p = 0.0006), and protein S (109% vs. 89%, p < 0.0001) were higher than in controls. In contrast, antithrombin (97% vs. 102%, p = 0.0025) was higher in control patients. In multivariate analyses controlling for insulin sensitivity, body fat compartments, and genotype variants (PNPLA3I148MM/MI/TM6SF2E167kK/kE), only protein C and protein S remained significantly increased in fatty liver. ConclusionsBody fat distribution is significantly associated with alterations of procoagulant and anticoagulant parameters. Liver fat plays a key role in the regulation of protein C and protein S, suggesting a potential counteracting mechanism to the prothrombotic state in subjects with prediabetes and fatty liver.

Fatty acid profiles of estuarine macroalgae are biomarkers of anthropogenic pressures: Development and application of a multivariate pressure index

Transitional ecosystems are among the most degraded ecosystems worldwide, with several groups of organisms investigated for their reliability as biological indicators of human-driven disturbances. Recently non-traditional biochemical biomarkers such as an individual's fatty acids profile have been identified as promising tools for assessing contaminant exposure. In this work, two abundant Atlantic benthic macroalgae (Ulva lactuca and Fucus vesiculosus species) were surveyed in three mudflat areas of the highly urbanized Tejo estuary, with increasing anthropogenic disturbance degrees (Alcochete, Rosário and Seixal mudflats, increasing in contamination by this order) and their fatty acids evaluated as potential biomarkers for exposure to contaminants known to have toxic effects on biota. In terms of contamination the metal pollution index of all the compartments analysed (sediment bioavailable and total metal concentrations and thallus metal concentrations) revealed the same tendencies with lower contamination levels in Alcochete, intermediate in Rosário and high contamination levels in Seixal. In the thallus of U. lactuca thallus could be observed a strong decrease in C18-fatty acids along the contamination gradient, likely due to lipid peroxidation from metal-generated reactive oxygen species. Nevertheless, an increase in stearic and hexadecatrienoic acids in the thallus from the most contaminated site suggested counteractive mechanisms maintain the production of C18-fatty acid pool. A similar response was found in F. vesiculosus but with palmitic acid acting as precursor for the synthesis of stearic acid, allowing the maintenance of oleic and linoleic acids levels in the membranes to counteract oxidative stress. Beyond the physiological interest of these mechanisms, fatty acid profiles were used to develop a novel multivariate pressure index (Multi-PI), that beyond the contaminant concentration would reflect the response of these biomonitor species towards anthropogenic disturbance, through the evaluation of fatty acid profiles, which are also key molecules from a trophic perspective within the estuarine system. The Multi-PI efficiency in responding to different environmental contamination degrees, was substantiated by strong and positive correlations with thallus and sediment contamination. This indicated that fatty acid profiles reflect thallus and benthic habitat contamination and are efficient biomarkers of environmental metal contamination. Therefore, the sessile and abundant nature of benthic macroalgae allied to their fatty acid responses can be leveraged as suitable biomarkers for contaminant monitoring in future impact assessment and ecotoxicology studies.