International justice as a way to settle conflicts in the world arena : the idea and the implementation

The purpose of this article is to identify the processes regarding the emergence of international justice and the start of international courts functioning. Dialectical, phenomenological and historical methods of analysis is the methodological basis of the article to allow to identify the international justice essence and the specifics of this phenomenon implementation in the initial stages of its development. In the course of this analysis the authors came to the conclusion that the international justice concept formation occurred in the turn of the XIXth and XXth centuries while the international justice formation took place in the first half of the XXth century.peer-reviewe

Integration of economic shifts in the european development in the second half of the XXth century

Purpose: The article analyzes those processes having initiated the development of the European and political integration. The article is focused on the genesis and the development of the Council for Mutual Economic Assistance, the European Union, NATO and the Warsaw Pact. Design/Methodology/Approach: By applying the system analysis method as well as dialectical and historical methods, the authors have attempted to reveal the significance of those events resulted in modern international organizations establishment. Findings: Authors have analyzed the XX century trends in integration and highlighted Western Europe as the most productive in the process. Authors have provided the USSR and post-USSR integration overview to reveal the European development patterns. Practical Implications: The research results may be implemented into political and educational courses as well as to be used by official authorities. Originality/Value: The main contribution of this study is the deep integration trends'analysis and the emphasis on the unipolar-bipolar-multipolar world's concept.peer-reviewe

Increased circulating ANG II and TNF-α represents important risk factors in obese Saudi adults with hypertension irrespective of diabetic status and BMI

Central adiposity is a significant determinant of obesity-related hypertension risk, which may arise due to the pathogenic inflammatory nature of the abdominal fat depot. However, the influence of pro-inflammatory adipokines on blood pressure in the obese hypertensive phenotype has not been well established in Saudi subjects. As such, our study investigated whether inflammatory factors may represent useful biomarkers to delineate hypertension risk in a Saudi cohort with and without hypertension and/or diabetes mellitus type 2 (DMT2). Subjects were subdivided into four groups: healthy lean controls (age: 47.9±5.1 yr; BMI: 22.9±2.1 Kg/m2), non-hypertensive obese (age: 46.1±5.0 yr; BMI: 33.7±4.2 Kg/m2), hypertensive obese (age: 48.6±6.1 yr; BMI: 36.5±7.7 Kg/m2) and hypertensive obese with DMT2 (age: 50.8±6.0 yr; BMI: 35.3±6.7 Kg/m2). Anthropometric data were collected from all subjects and fasting blood samples were utilized for biochemical analysis. Serum angiotensin II (ANG II) levels were elevated in hypertensive obese (p<0.05) and hypertensive obese with DMT2 (p<0.001) compared with normotensive controls. Systolic blood pressure was positively associated with BMI (p<0.001), glucose (p<0.001), insulin (p<0.05), HOMA-IR (p<0.001), leptin (p<0.01), TNF-α (p<0.001) and ANG II (p<0.05). Associations between ANG II and TNF-α with systolic blood pressure remained significant after controlling for BMI. Additionally CRP (p<0.05), leptin (p<0.001) and leptin/adiponectin ratio (p<0.001) were also significantly associated with the hypertension phenotype. In conclusion our data suggests that circulating pro-inflammatory adipokines, particularly ANG II and, TNF-α, represent important factors associated with a hypertension phenotype and may directly contribute to predicting and exacerbating hypertension risk

Extreme genomic erosion after recurrent demographic bottlenecks in the highly endangered Iberian lynx

Background: Genomic studies of endangered species provide insights into their evolution and demographic history, reveal patterns of genomic erosion that might limit their viability, and offer tools for their effective conservation. The Iberian lynx (Lynx pardinus) is the most endangered felid and a unique example of a species on the brink of extinction. Results: We generate the first annotated draft of the Iberian lynx genome and carry out genome-based analyses of lynx demography, evolution, and population genetics. We identify a series of severe population bottlenecks in the history of the Iberian lynx that predate its known demographic decline during the 20th century and have greatly impacted its genome evolution. We observe drastically reduced rates of weak-to-strong substitutions associated with GC-biased gene conversion and increased rates of fixation of transposable elements. We also find multiple signatures of genetic erosion in the two remnant Iberian lynx populations, including a high frequency of potentially deleterious variants and substitutions, as well as the lowest genome-wide genetic diversity reported so far in any species. Conclusions: The genomic features observed in the Iberian lynx genome may hamper short- and long-term viability through reduced fitness and adaptive potential. The knowledge and resources developed in this study will boost the research on felid evolution and conservation genomics and will benefit the ongoing conservation and management of this emblematic species

Differential IL-1β secretion by monocyte subsets is regulated by Hsp27 through modulating mRNA stability.

Monocytes play a central role in regulating inflammation in response to infection or injury, and during auto-inflammatory diseases. Human blood contains classical, intermediate and non-classical monocyte subsets that each express characteristic patterns of cell surface CD16 and CD14; each subset also has specific functional properties, but the mechanisms underlying many of their distinctive features are undefined. Of particular interest is how monocyte subsets regulate secretion of the apical pro-inflammatory cytokine IL-1β, which is central to the initiation of immune responses but is also implicated in the pathology of various auto-immune/auto-inflammatory conditions. Here we show that primary human non-classical monocytes, exposed to LPS or LPS + BzATP (3'-O-(4-benzoyl)benzyl-ATP, a P2X7R agonist), produce approx. 80% less IL-1β than intermediate or classical monocytes. Despite their low CD14 expression, LPS-sensing, caspase-1 activation and P2X7R activity were comparable in non-classical monocytes to other subsets: their diminished ability to produce IL-1β instead arose from 50% increased IL-1β mRNA decay rates, mediated by Hsp27. These findings identify the Hsp27 pathway as a novel therapeutic target for the management of conditions featuring dysregulated IL-1β production, and represent an advancement in understanding of both physiological inflammatory responses and the pathogenesis of inflammatory diseases involving monocyte-derived IL-1β

Ключевые звенья патогенеза токсической миокардиопатии

Goal. To identify key links in the pathogenesis of toxic myocardiopathy in conditions of endogenous intoxication in peritonitis. Materials and methods. Experimental studies were carried out on dogs (n = 24). The model of purulent fecal peritonitis. We studied the run-time content of toxic products in blood plasma, the lipid composition, the intensity of lipid peroxidation, the activity of phospholipase A2 and superoxide dismutase, and hypoxia of myocardial tissue. We evaluated loss of water and proteins, electrogenesis of the myocardium cells and changes in the ECG parameters. We also performed histological examination of the myocardial tissue. Results. Experimental studies in dogs showed that the development of endotoxicosis of peritoneal origin is accompanied by significant metabolic disorders and cardiac malfunction leading to the development of myocardiopathy. The most important role in the development and progression of myocardial damage in endotoxicosis is played by biomembrane damage and disruption of associated processes. The main processes are quantitative and qualitative modifications of phospholipids in cardiac cell membranes. Conclusion. The obtained data demonstrate the key role of the interrelation between dyslipidemia in the investigated cellular structures and intensification of lipid peroxidation, an increase in phospholipase A 2 activity, and hypoxia; which confirms the significance of these processes in destabilization of the phospholipid matrix of biomembranes.Цель. Выявить ключевые звенья патогенеза токсической миокардиопатии в условиях эндогенной интоксикации при перитоните. Материалы и методы. Проведены экспериментальные исследования на собаках (n = 24). Смоделирован гнойный каловый перитонит. В динамике процесса исследовали содержание токсических продуктов в плазме крови, липидный состав, интенсивность процессов перекисного окисления липидов и активность фосфолипазы А2, супероксиддисмутазы, показатели гипоксии ткани миокарда. Оценивали трофику и электрогенез миокарда, изменения показателей электрокардиограммы. Проводили гистологическое исследование ткани миокарда. Результаты. Развитие эндотоксикоза перитонеального генеза вызывает значительные нарушения метаболизма и функции сердца с развитием миокардиопатии. Ключевую роль в развитии и прогрессировании повреждений сердца при эндотоксикозе играет нарушение целостности биомембран и расстройство процессов, реализующихся с их участием. К числу основных среди них относят количественную и качественную модификацию фосфолипидов мембран кардиоцитов. Заключение. Полученные факты свидетельствуют о ключевой роли сопряженности дислипидных явлений в исследованных клеточных структурах с интенсификацией перекисного окисления липидов, увеличением активности фосфолипазы А2, гипоксией, что подтверждает значимость данных процессов в дестабилизации фосфолипидной матрицы биомембран

Management of MDR-TB in HIV co-infected patients in Eastern Europe: Results from the TB:HIV study

Objectives Mortality among HIV patients with tuberculosis (TB) remains high in Eastern Europe (EE), but details of TB and HIV management remain scarce. Methods In this prospective study, we describe the TB treatment regimens of patients with multi-drug resistant (MDR) TB and use of antiretroviral therapy (ART). Results A total of 105 HIV-positive patients had MDR-TB (including 33 with extensive drug resistance) and 130 pan-susceptible TB. Adequate initial TB treatment was provided for 8% of patients with MDR-TB compared with 80% of those with pan-susceptible TB. By twelve months, an estimated 57.3% (95%CI 41.5\u201374.1) of MDR-TB patients had started adequate treatment. While 67% received ART, HIV-RNA suppression was demonstrated in only 23%. Conclusions Our results show that internationally recommended MDR-TB treatment regimens were infrequently used and that ART use and viral suppression was well below the target of 90%, reflecting the challenging patient population and the environment in which health care is provided. Urgent improvement of management of patients with TB/HIV in EE, in particular for those with MDR-TB, is needed and includes widespread access to rapid TB diagnostics, better access to and use of second-line TB drugs, timely ART initiation with viral load monitoring, and integration of TB/HIV care

Clinical and organizational factors associated with mortality during the peak of first COVID-19 wave: the global UNITE-COVID study

Purpose: To accommodate the unprecedented number of critically ill patients with pneumonia caused by coronavirus disease 2019 (COVID-19) expansion of the capacity of intensive care unit (ICU) to clinical areas not previously used for critical care was necessary. We describe the global burden of COVID-19 admissions and the clinical and organizational characteristics associated with outcomes in critically ill COVID-19 patients. Methods: Multicenter, international, point prevalence study, including adult patients with SARS-CoV-2 infection confirmed by polymerase chain reaction (PCR) and a diagnosis of COVID-19 admitted to ICU between February 15th and May 15th, 2020. Results: 4994 patients from 280 ICUs in 46 countries were included. Included ICUs increased their total capacity from 4931 to 7630 beds, deploying personnel from other areas. Overall, 1986 (39.8%) patients were admitted to surge capacity beds. Invasive ventilation at admission was present in 2325 (46.5%) patients and was required during ICU stay in 85.8% of patients. 60-day mortality was 33.9% (IQR across units: 20%–50%) and ICU mortality 32.7%. Older age, invasive mechanical ventilation, and acute kidney injury (AKI) were associated with increased mortality. These associations were also confirmed specifically in mechanically ventilated patients. Admission to surge capacity beds was not associated with mortality, even after controlling for other factors. Conclusions: ICUs responded to the increase in COVID-19 patients by increasing bed availability and staff, admitting up to 40% of patients in surge capacity beds. Although mortality in this population was high, admission to a surge capacity bed was not associated with increased mortality. Older age, invasive mechanical ventilation, and AKI were identified as the strongest predictors of mortality

Post-transcriptional control during chronic inflammation and cancer: a focus on AU-rich elements

A considerable number of genes that code for AU-rich mRNAs including cytokines, growth factors, transcriptional factors, and certain receptors are involved in both chronic inflammation and cancer. Overexpression of these genes is affected by aberrations or by prolonged activation of several signaling pathways. AU-rich elements (ARE) are important cis-acting short sequences in the 3′UTR that mediate recognition of an array of RNA-binding proteins and affect mRNA stability and translation. This review addresses the cellular and molecular mechanisms that are common between inflammation and cancer and that also govern ARE-mediated post-transcriptional control. The first part examines the role of the ARE-genes in inflammation and cancer and sequence characteristics of AU-rich elements. The second part addresses the common signaling pathways in inflammation and cancer that regulate the ARE-mediated pathways and how their deregulations affect ARE-gene regulation and disease outcome