Differential sensitivity of brainstem vs cortical astrocytes to changes in pH reveals functional regional specialization of astroglia

Astrocytes might function as brain interoceptors capable of detecting different (chemo)sensory modalities and transmitting sensory information to the relevant neural networks controlling vital functions. For example, astrocytes which reside near the ventral surface of the brainstem (central respiratory chemosensitive area) respond to physiological decreases in pH with vigorous elevations in intracellular Ca(2+) and release of ATP. ATP transmits astroglial excitation to the brainstem respiratory network and contributes to adaptive changes in lung ventilation. Here we show that in terms of pH-sensitivity ventral brainstem astrocytes are clearly distinct from astrocytes residing in the cerebral cortex. We monitored vesicular fusion in cultured rat brainstem astrocytes using total internal reflection fluorescence microscopy and found that approximately 35% of them respond to acidification with an increased rate of exocytosis of ATP-containing vesicular compartments. These fusion events require intracellular Ca(2+) signaling and are independent of autocrine ATP actions. In contrast, the rate of vesicular fusion in cultured cortical astrocytes is not affected by changes in pH. Compared to cortical astrocytes, ventral brainstem astrocytes display higher levels of expression of genes encoding proteins associated with ATP vesicular transport and fusion, including vesicle-associated membrane protein-3 and vesicular nucleotide transporter. These results suggest that astrocytes residing in different parts of the rat brain are functionally specialized. In contrast to cortical astrocytes, astrocytes of the brainstem chemosensitive area(s) possess signaling properties which are functionally relevant – they are able to sense changes in pH and respond to acidification with enhanced vesicular release of ATP

Unidirectional convective flows of a viscous incompressible fluid with slippage in a closed layer

An exact solution describing the flow of a viscous incompressible fluid in a closed horizontal layer is obtained in view of the Navier slip condition and the inhomogeneous pressure distribution on one of the layer boundaries. The principal possibility of velocity field stratification and the dependence of the number of stratification points on the slip length are demonstrated. © 2019 Author(s)

Genetic Polymorphism of beta1-adrenergic Receptors and the Effect on the Clinical Efficacy of beta-adrenoblockers

Beta-adrenergic blockers are a valuable class of cardiovascular drugs and are widely used in the treatment of arterial hypertension (AH), coronary heart disease, chronic heart failure (CHF), cardiac arrhythmias, significantly improving the prognosis of patients. However, the clinical efficacy of betablockers is largely dependent on the genetic polymorphism of beta1-adrenergic receptors (ADRB1). The aim of the review was a systematic analysis of scientific data from pharmacogenetic studies on the role of beta1-adrenergic receptor polymorphism in the clinical efficacy of beta-blockers in the treatment of hypertension, chronic heart failure, and atrial fibrillation. The results of clinical trials and meta-analyzes were used. Of greatest importance is the genetic polymorphism of beta1-adrenergic receptors of two loci – Arg389Gly and Ser49Gly; the frequency of occurrence of variant and less functionally active alleles Gly389 and Gly49 in Europeans reaches 27% and 15%. The variant Gly389 allele has reduced functional activity and carriers have a weak response to the use of beta-blockers. In carriers of variant alleles Gly389 and Gly49 a reduced hypotensive effect on the use of beta-blockers was observed, and in studies of long-term efficacy, carriage of variant alleles was accompanied by an increase in the frequency and risk of unfavorable outcomes of hypertension. In pharmacogenetic studies, a reduced effect of the effect on myocardial remodeling in patients with CHF for beta-blockers in carriers of the variant Gly389 allele were confirmed. According to two meta-analyzes of trials on use of beta-blockers in patients with CHF, the frequency of increased left ventricle ejection fraction was significantly higher in carriers of the wild Arg389Arg gene type (risk ratio=1.83, p=0,001). In contrast, in atrial fibrillation, the frequency of rhythm control with beta-blockers was achieved better in the presence of the variant allele Gly389 with “loss of function”. Another polymorphic Gly49 allele plays a role in desensitization and down-regulation of beta1-receptor activity, although clinically this effect has been less obvious and contradictory. However, in studies, a more pronounced clinical effect of beta-blockers was observed in carriers of the wild genotype Ser49Ser, as well as in carriers of the haplotype Ser49Ser/Arg389Arg. Thus, genetic polymorphism ADRB1 may be another important predictor of the effectiveness of beta-blockers in clinical practice, which must be taken into account in the treatment of cardiovascular diseases

Development of an insurance industry image assessment index

The article discusses the results of the study of consumer attitudes towards the insurance sector in the Russian Federation. A low level of financial literacy, cases of fraud by insurers lead to the formation of a negative image of the insurance industry, even if the respondents have a positive experience of using insurance products. In world practice the relationship between reputation management of companies and their financial condition has been proven, however, a quantitative assessment of the insurance sector image has been not carried out earlier. The article offers a methodology for assessing the insurance sector image? using the author’s index, and provides an example of its calculation based on the Russian insurance market. The developed indicator will allows to objectively assess the dynamics of consumer attitudes to insurance, and to conduct a cross-country comparison of the indicator

Prospects for digital transformation of the monetary systems

The active digitalization of financial markets generates new types of digital financial assets, and also raises questions about prospects of the national monetary systems development, taking into account the emerging digital financial instruments. The authors present the results of a study conducted via interviewing respondents about their attitude to cryptocurrencies, about the likelihood of cashless economies, and about the impact of economy digitalization on changing people’s lives. Current scientific studies show that a significant part of authors is inclined to believe that current digitalization trends will lead to the complete disappearance of cash, including cryptocurrencies will play an important role in this process. Low financial literacy, possible failures in electronic payment systems, the difficulty of adaptation for certain groups of the population are the reasons that delay the transition to cashless economies. However, a significant number of advantages that digital assets provide for the development of the economy, and the positive attitude of society to the changes taking place in the process of digital transformation, contribute to a further change in the monetary system

The Effect of the Russian Subnational Debt on the Socio-economic Development of the Region

The actual problem currently in Russia is the high degree of differentiation level of socio-economic development of constituent entities of the Russian Federation. The specified uneven development is a significant problem, requiring prudent and gradual approach. An important point is to determine the optimal size and form of regional borrowing, contributing to the socio-economic development of the region. This article examines the structure of the borrowing regions. Many regions have a significant amount of borrowing in the form of budget loans. Outlines the problem caused by the miscalculations of the regional authorities when conducting its own financial policy, and a more global objective reasons, which are a consequence of the current crisis situation in economy of the Russian Federation and the disparity of economic development. The basis for the paper is drawn from actual official data describing the state of the market of regional and municipal borrowing. Used methods of system analysis, comparison and clustering.The result is proved in the article that on the one hand the issue of securities does not stimulate socio-economic development of the region, on the other hand in the current situation, the desired reduction provide budget loans should pay attention of regions in the possible form of borrowing. With the improvement of the situation on the debt market regions will be stimulated to ensure that the overwhelming proportion of their debt would be the consequence of market borrowings, primarily in the form of securities.The article presents a comparison of different forms of regional borrowing and identified deficiencies inherent in different types of borrowing. It is concluded that a bank loan is the most popular form of market borrowing, as it has in relation to issuance of bonds less amount of disadvantages. According to the authors, for the development of the bonded form of the borrowing of regions should consider the infrastructure of the state support

Rating Agencies in Russia and their Influence on Subfederal Borrowing

In Russia, the topical issue today is the high volume of obligations of regions against the federal budget. These liabilities have been caused by the current crisis in the Russian economy as well as by the disproportionate economic development, and this issue requires an adequate solution. It is planned that later on the regions will develop market borrowings first of all in form of securities. This article analyzes the infrastructural component of the market of subfederal and municipal borrowings - rating agencies in Russia. The article is based on the actual official data characterizing the current state of the market of regional and municipal borrowings, data from credit rating agencies were used as well. There were used systems analysis method, comparative approach, and clustering method. The article results in the conclusion that ratings of the international agencies are not always unbiased politically, not economically, which negatively affects the development of the debt market as a whole and the market of subfederal and municipal bonds, in particular. The development of the Russian credit rating agencies has a number of advantages and will contribute to the development of the indicated market in the future

Summary of updates to the 2021 European Society of Cardiology Guidelines for the diagnosis and treatment of acute and chronic heart failure

The article provides a summary of the 2021 European Society of Cardiology (ESC) Guidelines for the diagnosis and treatment of acute and chronic heart failure (CHF). The most significant changes for general practitioners, internists and primary care cardiologists, from our point of view, regards etiology, terminology, as well as algorithms for diagnosing and treating CHF in accordance with phenotypes, new indications to a number of drugs, in particular sodium-glucose cotransporter type 2 inhibitors (dapagliflozin and empagliflozin) with assignment of class I recommended therapy and vericiguat. The article discusses the diagnostic criteria for different heart failure phenotypes, the potential of treating patients with heart failure mildly reduced and preserved ejection fraction

Typology of risks of territories of advanced development

The article deals with the one of the most difficult aspects of the implementation of public-private partnership (PPP) - risk management. That partnership is the answer to the solution of problems with the choice of an effective way of development of transport, social, communal and other infrastructure. The practice of using PPP forms is gaining popularity in the territory of Russia. The authors considers the matters of the Russian economy improvement by readjustment the existing risk management paradigm of a PPP. An integral part of highly professional risk management is the definition of management objects in the economic sphere. A number of controversial issues related to classifications of risks of PPP is raised in the article. Since the domestic theory has not yet solved the problem of clear and comprehensive risk identification in the implementation of projects based on PPP, it is necessary to develop such a classification is now becoming particularly relevant. Various available points of view on this issue are analyzed. The authors propose their position on the classification of risks for the territories of advanced development proceeding from the environment of their origin. The developed classification will help stimulate the PPP market from a practical point of view in different sectors. The modern advantages of using advanced development territories in the Russian Federation and recommended them as an organizational model of PPP are revealed. It should be noted that to date there is no single system of documents for the development of regional infrastructure, which causes a lot of uncertainties in the course of making a decision on this transaction

Features of selecting boundary conditions when describing flows of stratified fluids

The article discusses the selection of boundary conditions at the boundary between adjacent layers in a stratified viscous incompressible fluid. It is shown that the "continuity condition + differentiability condition" pair traditionally used in many disciplines gives physically unjustified properties of the resulting exact solution for the velocity field. Although the condition for the differentiability of velocities is close in mathematical form to the stress continuity condition (by virtue of Newton's law), in terms of physics, taking these conditions into account gives fundamentally different properties of the exact solution of the Navier-Stokes system of equations. It is shown that the consideration of the "the velocity field continuity condition + the stress field continuity condition" pair is more adequate to the physics of the process, which is consistent with the hypothesis of continuity. © 2021 Elsevier B.V.. All rights reserved