Legal certainty in law enforcement through the prism of ECtHR decisions

The problems of legal certainty and legal uncertainty are growing significantly in the field of lawmaking and law enforcement. Thus, the threatening consequences of this are the weakening of the rule of law around the world and the growing number of Ukrainian citizens applying to the European Court of Human Rights (ECtHR). The article traces the brief genesis of the principle of "res judicata", emphasizes the various manifestations and forms of legal certainty, and clarifies two groups of requirements for it. In the study, the main attention is paid to the peculiarities of legal certainty in the field of law enforcement. The article is aimed at determining the features and requirements of the principle of legal certainty in court proceedings based on analysis and generalization of ECtHR decisions. It is substantiated that in the generalized form the elemental composition of the principle of certainty in law enforcement includes: requirements for interpretation (in particular, judicial) of normative legal acts and separate norms; legality of resolving legal conflicts and eliminating gaps in current legislation; stability of court decisions; unity of judicial practice. The case law of European judicial institutions in matters of legal certainty is characterized by the position that the problem should be resolved in each case taking into account the facts of the case, their analysis in terms of identity, the relationship between them, as well as their proneness, a combination of stability and dynamism, general and special. Research methods used by the authors of the article include analysis, synthesis, induction, deduction, comparative-legal, formal-legal and logical-legal methods

Epobis is a Nonerythropoietic and Neuroprotective Agonist of the Erythropoietin Receptor with Anti-Inflammatory and Memory Enhancing Effects

The cytokine erythropoietin (EPO) stimulates proliferation and differentiation of erythroid progenitor cells. Moreover, EPO has neuroprotective, anti-inflammatory, and antioxidative effects, but the use of EPO as a neuroprotective agent is hampered by its erythropoietic activity. We have recently designed the synthetic, dendrimeric peptide, Epobis, derived from the sequence of human EPO. This peptide binds the EPO receptor and promotes neuritogenesis and neuronal cell survival. Here we demonstrate that Epobis in vitro promotes neuritogenesis in primary motoneurons and has anti-inflammatory effects as demonstrated by its ability to decrease TNF release from activated AMJ2-C8 macrophages and rat primary microglia. When administered systemically Epobis is detectable in both plasma and cerebrospinal fluid, demonstrating that the peptide crosses the blood-brain barrier. Importantly, Epobis is not erythropoietic, but systemic administration of Epobis in rats delays the clinical signs of experimental autoimmune encephalomyelitis, an animal model of multiple sclerosis, and the peptide has long-term, but not short-term, effects on working memory, detected as an improved social memory 3 days after administration. These data reveal Epobis to be a nonerythropoietic and neuroprotective EPO receptor agonist with anti-inflammatory and memory enhancing properties

СУЧАСНІ ФОРМИ ОРГАНІЗАЦІЇ ПІСЛЯДИПЛОМНОГО НАВЧАННЯ ТА БЕЗПЕРЕРВНОГО ПРОФЕСІЙНОГО РОЗВИТКУ МЕДИЧНИХ ПРАЦІВНИКІВ

The aim of the work – to highlight some aspects of introduction of modern educational technologies and new forms of organization of training in postgraduate education and continuous professional development of doctors are described in this article. The main body. It is stated, that pedagogical innovations are aimed at the optimizing of the teaching on the principle of the correspondence of the content of the training to the actual conditions of the doctor’s work. The experience of introducing of intermittent courses of thematic improvement and organization of intensive training of doctors on topical problems of modern medicine is presented.Conclusion. The necessity of using various educational models, which based on the achievements of medical science and practice in accordance with the needs of the medical sector and each target group of subjects of training.Мета роботи – висвітлити деякі аспекти із запровадження сучасних освітніх технологій та новітніх форм організації навчання  у післядипломну підготовку і безперервний професійний розвиток лікарів.Основна частина. Наведено, що педагогічні інновації мають на меті  оптимізацію навчання за принципом відповідності змісту навчання реальним умовам роботи лікаря. Представлено досвід із запровадження переривчатих курсів тематичного удосконалення та організації інтенсивного навчання лікарів з актуальних проблем сучасної медицини.Висновок. Необхідним є застосування різноманітних навчальних моделей на підставі досягнень медичної науки і практики відповідно до потреб медичної галузі та  кожної цільової групи суб’єктів навчання

ВИКОРИСТАННЯ МЕТОДИК СИМУЛЯЦІЙНОГО НАВЧАННЯ У ПІДВИЩЕННІ ПРОФЕСІЙНОЇ КОМПЕТЕНЦІЇ ЛІКАРІВ ТА ПАРАМЕДИКІВ НА КАФЕДРАХ ДЗ “ЗМАПО МОЗ УКРАЇНИ”

The modeling techniques, which implemented in the postgraduate education of doctors, and evaluating of competency by Bloome classification were analyzed in this article. Conclusions about the role of use of simulation methods as the main part of relationship of the educational process and the real clinical practice in post-graduate education of physicians were made.У статті представлено аналіз та роль симуляційних методик, впроваджених на кафедрах ДЗ “ЗМАПО МОЗ України”, та оцінку отриманих лікарями компетенцій за класифікацією Блума. Показано, що використання симуляційних методик дозволяє відтворити тісний зв’язок навчального процесу з практикою і максимальну реалістичність клінічної ситуації у післядипломній освіті лікарів

NAMPT-mediated NAD+ biosynthesis is indispensable for adipose tissue plasticity and development of obesity

Objective: The ability of adipose tissue to expand and contract in response to fluctuations in nutrient availability is essential for the maintenance of whole-body metabolic homeostasis. Given the nutrient scarcity that mammals faced for millions of years, programs involved in this adipose plasticity were likely evolved to be highly efficient in promoting lipid storage. Ironically, this previously advantageous feature may now represent a metabolic liability given the caloric excess of modern society. We speculate that nicotinamide adenine dinucleotide (NAD+) biosynthesis exemplifies this concept. Indeed NAD+/NADH metabolism in fat tissue has been previously linked with obesity, yet whether it plays a causal role in diet-induced adiposity is unknown. Here we investigated how the NAD+ biosynthetic enzyme nicotinamide phosphoribosyltransferase (NAMPT) supports adipose plasticity and the pathological progression to obesity. Methods: We utilized a newly generated Nampt loss-of-function model to investigate the tissue-specific and systemic metabolic consequences of adipose NAD+ deficiency. Energy expenditure, glycemic control, tissue structure, and gene expression were assessed in the contexts of a high dietary fat burden as well as the transition back to normal chow diet. Results: Fat-specific Nampt knockout (FANKO) mice were completely resistant to high fat diet (HFD)-induced obesity. This was driven in part by reduced food intake. Furthermore, HFD-fed FANKO mice were unable to undergo healthy expansion of adipose tissue mass, and adipose depots were rendered fibrotic with markedly reduced mitochondrial respiratory capacity. Yet, surprisingly, HFD-fed FANKO mice exhibited improved glucose tolerance compared to control littermates. Removing the HFD burden largely reversed adipose fibrosis and dysfunction in FANKO animals whereas the improved glucose tolerance persisted. Conclusions: These findings indicate that adipose NAMPT plays an essential role in handling dietary lipid to modulate fat tissue plasticity, food intake, and systemic glucose homeostasis. Keywords: Adipose metabolism, Obesity, NAMPT, NAD+ synthesis, Energy homeostasis, Adipose plasticity, Glucose homeostasi

To the Мemory of the Scientist, Teacher, Human: Dadicated to 65-th Аnniversary of Professor Anatolyj Fedosov

Висвітлено основні віхи життєвого шляху відомого вченого фізика професора А. В. Федосова.;The paper presents the career and scientific achievements of well-known physicist Professor Anatolyj Fedosov

Cell selectivity in succinate receptor SUCNR1/GPR91 signaling in skeletal muscle

Succinate is released by skeletal muscle during exercise and activates SUCNR1/GPR91. Signaling of SUCNR1 is involved in metabolite-sensing paracrine communication in skeletal muscle during exercise. However, the specific cell types responding to succinate and the directionality of communication are unclear. We aim to characterize the expression of SUCNR1 in human skeletal muscle. De novo analysis of transcriptomic datasets demonstrated that SUCNR1 mRNA is expressed in immune, adipose, and liver tissues, but scarce in skeletal muscle. In human tissues, SUCNR1 mRNA was associated with macrophage markers. Single-cell RNA sequencing and fluorescent RNAscope demonstrated that in human skeletal muscle, SUCNR1 mRNA is not expressed in muscle fibers but coincided with macrophage populations. Human M2-polarized macrophages exhibit high levels of SUCNR1 mRNA and stimulation with selective agonists of SUCNR1 triggered Gq- and Gi-coupled signaling. Primary human skeletal muscle cells were unresponsive to SUCNR1 agonists. In conclusion, SUCNR1 is not expressed in muscle cells and its role in the adaptive response of skeletal muscle to exercise is most likely mediated via paracrine mechanisms involving M2-like macrophages within the muscle. NEW & NOTEWORTHY Macrophages but not skeletal muscle cells respond to extracellular succinate via SUCNR1/GPR91

Type 2 diabetes is associated with increased circulating levels of 3-hydroxydecanoate activating GPR84 and neutrophil migration

Obesity and diabetes are associated with inflammation and altered plasma levels of several metabolites, which may be involved in disease progression. Some metabolites can activate G protein-coupled receptors (GPCRs) expressed on immune cells where they can modulate metabolic inflammation. Here, we find that 3-hydroxydecanoate is enriched in the circulation of obese individuals with type 2 diabetes (T2D) compared with nondiabetic controls. Administration of 3-hydroxydecanoate to mice promotes immune cell recruitment to adipose tissue, which was associated with adipose inflammation and increased fasting insulin levels. Furthermore, we demonstrate that 3-hydroxydecanoate stimulates migration of primary human and mouse neutrophils, but not monocytes, through GPR84 and Gαi signaling in vitro. Our findings indicate that 3-hydroxydecanoate is a T2D-associated metabolite that increases inflammatory responses and may contribute to the chronic inflammation observed in diabetes