[FORMATION OF THE NOTION OF «QUALITY OF LIFE¼, CONCEPTUALISATION AND METHODOLOGICAL ASPECTS (LITERATURE REVIEW)].

Quality of life (QoL) is an important health outcome and represents the primary aim of all medical interventions. The term QoL has been is frequently used in medical and philosophical literature in recent decades and has become an important concept and goal of public health research. Traditionally, biomedical results rather than QoL were the basic endpoints in clinical and public health research. However, recent research is increasingly focusing on the study of QoL in patients and the making use of QoL assessment has increased considerably. The concept of QoL has led to extensive research and has been used by the professional medical community in the treatment of a broad array of diseases. Literature search methods included database searches Scopus, Web of Science, MedLine, the Cochrane Library. Historical trends in the concept of QoL are discussed in this article and issues related to the conceptual and methodological aspects of constructing QoL in the context of health care.

[DETERMINING THE LEVEL OF TECHNOLOGICAL READINESS OF DEVELOPMENTS IN MEDICINE BASED ON THE TRL METHODOLOGY].

The article discusses an approach to assessing the level of maturity of medical technologies based on the TRL (technology readiness level) methodology. The author presents a tool for planning scientific results and developments in the direction of «medical sciences¼ with a clear description of the expected results at each level of research and development. The levels of technological maturity of developments in the field of healthcare are described in detail, possible results and reporting forms for each level are presented, their differences are analyzed depending on the planned final product. Also presented are proposals for the distribution of powers between the state and business to finance the process of creating and implementing a new medical technology, depending on its stage of maturity.

Regulation of the clock gene expression in human adipose tissue by weight loss.

BACKGROUND: The circadian clock coordinates numerous metabolic processes to adapt physiological responses to light-dark and feeding regimens and is itself regulated by metabolic cues. The implication of the circadian clock in the regulation of energy balance and body weight is widely studied in rodents but not in humans. Here we investigated (1) whether the expression of clock genes in human adipose tissue is changed by weight loss and (2) whether these alterations are associated with metabolic parameters. SUBJECTS/METHODS: Subcutaneous adipose tissue (SAT) samples were collected before and after 8 weeks of weight loss on an 800 kcal per day hypocaloric diet (plus 200 g per day vegetables) at the same time of the day. Fifty overweight subjects who lost at least 8% weight after 8 weeks were selected for the study. The expression of 10 clock genes and key metabolic and inflammatory genes in adipose tissue was determined by quantitative real-time PCR. RESULTS: The expression of core clock genes PER2 and NR1D1 was increased after the weight loss. Correlations of PERIOD expression with body mass index (BMI) and serum total, high-density lipoprotein and low-density lipoprotein (LDL) cholesterol levels and of NR1D1 expression with total and LDL cholesterol were found that became non-significant after correction for multiple testing. Clock gene expression levels and their weight loss-induced changes tightly correlated with each other and with genes involved in fat metabolism (FASN, CPT1A, LPL, PPARG, PGC1A, ADIPOQ), energy metabolism (SIRT1), autophagy (LC3A, LC3B) and inflammatory response (NFKB1, NFKBIA, NLRP3, EMR1). CONCLUSION: Clock gene expression in human SAT is regulated by body weight changes and associated with BMI, serum cholesterol levels and the expression of metabolic and inflammatory genes. Our data confirm the tight crosstalk between molecular clock and metabolic and inflammatory pathways involved in adapting adipose tissue metabolism to changes of the energy intake in humans.

Glucose inhibits the insulin-induced activation of the insulin-degrading enzyme in HepG2 cells.

AIMS/HYPOTHESIS: Hepatic insulin degradation decreases in type 2 diabetes. Insulin-degrading enzyme (IDE) plays a key role in insulin degradation and its gene is located in a diabetes-associated chromosomal region. We hypothesised that IDE may be regulated by insulin and/or glucose in a liver cell model. To validate the observed regulation of IDE in vivo, we analysed biopsies of human adipose tissue during different clamp experiments in men. METHODS: Human hepatoma HepG2 cells were incubated in normal (1 g/l) or high (4.5 g/l) glucose medium and treated with insulin for 24 h. Catalytic activity, mRNA and protein levels of IDE were assessed. IDE mRNA levels were measured in biopsies of human subcutaneous adipose tissue before and at 240 min of hyperinsulinaemic, euglycaemic and hyperglycaemic clamps. RESULTS: In HepG2 cells, insulin increased IDE activity under normal glucose conditions with no change in IDE mRNA or protein levels. Under conditions of high glucose, insulin increased mRNA levels of IDE without changes in IDE activity. Both in normal and high glucose medium, insulin increased levels of the catalytically more active 15a IDE isoform compared with the 15b isoform. In subcutaneous adipose tissue, IDE mRNA levels were not significantly upregulated after euglycaemic or hyperglycaemic clamps. CONCLUSIONS/INTERPRETATION: Insulin increases IDE activity in HepG2 cells in normal but not in high glucose conditions. This disturbance cannot be explained by corresponding alterations in IDE protein levels or IDE splicing. The loss of insulin-induced regulation of IDE activity under hyperglycaemia may contribute to the reduced insulin extraction and peripheral hyperinsulinaemia in type 2 diabetes.

[Association of insulinase gene polymorphisms with type 2 diabetes mellitus in patients from the Moscow population].

Association of 13 single nucleotide polymorphisms (SNPs) of insulinase (IDE) gene with type 2 diabetes mellitus (T2D) in the Moscow population has been examined. Three polymorphic markers (rs7078413, rs7899603, and rs551266) associated with the risk of T2D development have been revealed. Allele and genotype frequency distribution for these three markers differed significantly only in the sample of females between T2D patients and control individuals, while only in case of rs7078413 SNP genotype frequencies varied significantly in the total population.

[On the reactions of the human nervous system to complex-frequency optical stimulation]. / O reaktsiiakh nervnoi sistemy cheloveka na kompleksno-chastotnye svetovye vozdeistviia.

A computerized system for precise stimulation and analysis of electroencephalographic (EEG) reactions to two simultaneously presented frequencies of sine-wave light (one constant, 13 Hz, and the other varying from 1 to 6 Hz and vice versa) was used to study the mechanisms of human brain reactivity to complex rhythmical stimulation. The frequencies were generated by computer and presented to the subjects by three different ways: as a result of their simple summation (additively), as a product of their multiplication (multiplicatively, amplitude modulation of constant frequency by the varying frequency), or by separate presentation to different eyes. The dynamics of electroencephalograms for different types of stimulation were compared. Under all three experimental conditions, the dynamics of EEG spectra has demonstrated the same general pattern of resonance activation, which was similar to that observed for the presented signals in the case of their amplitude modulation. Significant positive shifts in the functional state of subjects were observed as a result of stimulation. The results obtained show the leading role of the processes of amplitude modulation in the interaction of integrative, adaptive, and trace mechanisms of the brain functioning during human perception of complex rhythmical stimuli.

[Circadian clocks and energy metabolism: implications for health]. / Zirkadiane Uhren und Energiestoffwechsel: Implikationen für die Gesundheit.

On behavioural as well as physiological levels our daily life is regulated by the circadian clock - endogenous oscillators present in the hypothalamus and in peripheral tissues - which is believed to have evolved as an adaptation to Earth rotation around the Sun and its consequent 24 h dark-light cycle. Accumulative evidence suggests that the circadian clock plays a pivotal role for energy metabolism and energy homeostasis: many hormones, enzymes and transport systems involved in the regulation of energy metabolism have been shown to display circadian rhythms in their expression, secretion and/or activity patterns. The energy metabolism, in turn, can impact on the circadian clock - a process that is called entrainment. Thus, the circadian clock and energy metabolism are intimately intertwined. So far this interplay and its implications for health have not been understood very well. For health maintenance, however, it seems to be crucial to avoid any desynchronisation between the circadian clock and energy metabolism. Form a clinical point of view this might be important for the treatment of obesity and associated disorders and may lead to new life-style approaches.