[Digital transformation of healthcare: a competency-based approach].

The article substantiates the relevance of the study of the essence, tools and mechanisms of digital transformation of the health sector. A comparative assessment of the current health care system in the cities of the world is presented, trends in the use of end-to-end technologies for improving the health care system in Russia are revealed. The development of the health sector in modern conditions is based on the introduction of new information and communication technologies, for the proactive use of which, it is necessary to increase the digital skills and awareness of health workers and the population. The national projects of the Russian Federation «Health care¼ and «Digital economy¼ speak about the need to implement design solutions for the formation of competence models of personnel in the conditions of global digitalization. The formation of the digital contour of the health sector should be based on a clear understanding of the competence profile, its inclusion in the innovative health care system and the preservation of human capital. The use of competence approach to the digital transformation of healthcare contributes to improving the adaptability of the existing system of health organization to the new technological order provides the possibility of introducing cross-cutting technologies in the processes of decision-making to improve the accessibility and quality of care.

[Cytogenetic effects in the population in agricultural regions of the Kemerovo region].

There was performed an analysis of chromosomal aberrations in peripheral blood lymphocytes of the inhabitants of 9 settlements from 6 agricultural regions of the Kemerovo region. 267 children-adolescents and 124 adults not involved in the industry were examined. The average level of chromosomal aberrations was 2.65% in children and 3.35% in adults. It can be regarded as a background regional level. There was no revealed the modifying ability of such factors as gender age, presence of harmful habits (smoking) on the formation of the frequency of cytogenetic abnormalities in residents of rural areas of the Kemerovo region.

[Role of repair gene polymorphism in estimating the sensitivity of human genome to radon in concentrations exceeding maximum permissible level].

The paper gives the results of investigating chromosome aberrations in human peripheral blood lymphocytes due to DNA repair genes, such as hOGG1, ADPRT, APE1, XRCC1, XpG, XpC, XpD, and NBS1, upon long-term exposure to excess indoor radon concentrations. The frequency of chromosome aberrations was found to be significantly lower in the carriers of the genotype hOGG1 326 Ser/Ser (versus the variant Ser/Cys), APE1 148 Asp/Asp (versus Val/Ala and Ala/Ala). The study polymorphic systems were shown to be of value in giving rise to individual types of chromosome aberrations (single fragments and chromosome exchanges).

[Spread of carcinogenic and mutagenic effects in the population of Gornaia Shoria].

Mutagenic and carcinogenic effects were studied in the population of Gornaya Shoria, Kemerovo Region. The carcinogenic effects were evaluated on the basis of the data given by the Kemerovo regional cancer registry over 1990-2008. The standardized cancer morbidity index in Gornaya Shoria (342 per 100,000 population) exceeded the average index in the Kemerovo Region (286 per 100,000) in the same period. The mutagenic effects were estimated on the basis of the monitoring data on the frequency and spectrum of chromosomal aberrations in the peripheral blood lymphocytes of the dwellers of Gornaya Shoria for the 1992-2009 period. The mean level of chromosomal aberrations (5.31%) in the residents of Gornaya Shoria was found to be greater than the regional background mutation rate (2.86%) (p < 0.001). The values of individual aberration types (chromatid and chromosomal breaks, as well as chromosome-type exchange aberrations) were significantly higher in the dwellers of Gornaya Shoria than those in the basic control group. The revealed high mutagenic load in the inhabitants of Tashtagol District, Kemerovo Region, allows this area to be assigned to high genetic risk ones.

[Toxic and genetic risk assessments in children of Gornaya Shoria].

This comprehensive study assessed a number of environmental factors that were potentially able to induce genotoxic effects in man. A set of radiological, physicochemical, and bioindication techniques was used to estimate the quality of water, air, and soil in the places of residence and education of children and adolescents from the boarding school of the town of Tashtagol and schoolchildren from the village of Krasnoye, Kemerovo Region. Excess radon levels in the air of living spaces and classes, a small excess of the maximum allowable concentration of gross forms of heavy metals in individual soil samples, and high toxic effects in the Drosophila gametes exposed to air samples were revealed in the Tashtagol children having higher genotoxic effects in the lymphocyte than those in the Krasnoye village ones. The findings suggest that the marked genotoxic effects recorded over a long time in the lymphocytes of children and adolescents living in Tashtagol may be associated with the complex influence of the above factors. It is north supplementing further investigations by an extended chemical analysis of water, air, snow, and soil samples taken in the places of residence and education of children.

[Genome sensitivity and genotoxic effects features in children-teenagers affected by radon radiation in living and educational environment].

The results of chromosomal aberration level and spectrum study in 48-hours peripheral blood lymphocytes cultures of 10-19 years old children-teenagers (n = 132, mean 14.2 +/- 0.16 years old) living in the south part of Kemerovskaya area Gornaya Shoria are presented. Mean metaphases with aberrations were 4.74 +/- 0.21% in studied group that is significantly higher (p < 0.01) than background level of this index in this region (Kemerovskaya area)- 2.62 +/- 0.29%. Aberrations frequencies of separate classes were 2.83 +/- 0.16 for single fragments; 1.89 +/- 0.14 for pair fragments; 0.05 +/- 0.02 for chromatide exchanges and 0.32 +/- 0.05 for chromosome type exchanges. Furthermore in 6 individuals (4.55%) were found Rogue cells that were contained polycentric, ring chromosomes and multiple pair dot fragments. The reasons of chromosomal aberrations frequency increasing in this mountain area inhabitants are discussed (ultrahigh radon radiation doses influence are included).

[Quantitative characteristics of chromosomal aberration frequency in the residents of the regions with different levels of cancer incidences].

We present the results of cytogenetic monitoring of the districts in Kemerovo region, which differ in standardized indices of cancer incidence. It has been shown that residents of the districts with high incidence of malignancies had higher average frequency of metaphases with chromosomal aberrations than the control group (4.06 +/- 0.12% and 2.76 +/- 0.13%, respectively). This difference is caused primarily by single or paired fragments. The increase in the frequency of aberrant metaphase incidence in the districts with elevated cancer frequency was observed both in the male and female groups as well as both in adults and children.

[A modification factor of spontaneous chromosomal aberrations in miner's towns and settlements].

The level and qualitative spectrum of spontaneous chromosomal aberrations (CA) were comparatively analyzed in the lymphocytes of 655 children and adolescents from the Kemerovo Region. The presented sample was divided into 3 groups according to the type of an inhabited locality: 1) small miner's towns; 2) large industrial towns; and 3) rural localities. The maximum frequency of CA (3.77 +/- 0.22%) was noted in a group of dwellers in the miner's towns; its minimum frequency (2.68 +/- 0.17%) among the rural inhabitants. The significant clastogenic effects (including the markers of radiation exposure) were detected in the miner's towns located in the southern part of the region, which represented mountain and submountain areas. At the same time, in the northern and western parts of the Kemerovo Region, the average frequencies of CA in children and adolescents did not exceed the control background values. Thus, the residence in the inhabited localities specializing in mining is not a factor of absolute toxicogenetic risk.

The HA-2 minor histocompatibility antigen is derived from a diallelic gene encoding a novel human class I myosin protein.

Human minor histocompatibility Ags (mHag) present significant barriers to successful bone marrow transplantation. However, the structure of human mHag and the basis for antigenic disparities are still largely unknown. Here we report the identification of the gene encoding the human mHag HA-2 as a previously unknown member of the class I myosin family, which we have designated MYO1G. The gene is located on the short arm of chromosome 7. Expression of this gene is limited to cells of hemopoietic origin, in keeping with the previously defined tissue expression of the HA-2 Ag. RT-PCR amplification of MYO1G from different individuals led to the identification of two genetic variants, designated MYO1G(V) and MYO1G(M). The former encodes the peptide sequence previously shown to be the HA-2 epitope (YIGEVLVSV), whereas the latter shows a single amino acid change in this peptide (YIGEVLVSM). This change has only a modest effect on peptide binding to the class I MHC-restricted element HLA-A*0201, and a minimal impact on recognition by T cells when added exogenously to target cells. Nonetheless, as detected using either T cells or mass spectrometry, this amino acid change results in a failure of the latter peptide to be presented at the surface of cells that express MYO1G(M) endogenously. These studies have thus identified a new mHag-encoding gene, and thereby provide additional information about both the genetic origins of human mHag as well as the underlying basis of an Ag-positive vs Ag-negative state.

The immunogenicity of a new human minor histocompatibility antigen results from differential antigen processing.

Minor histocompatibility antigens (mHAgs) present a significant impediment to organ and bone marrow transplantation between HLA-identical donor and recipient pairs. Here we report the identification of a new HLA-A*0201-restricted mHAg, HA-8. Designation of this mHAg as HA-8 is based on the nomenclature of Goulmy (Goulmy, E. 1996. Curr. Opin. Immunol. 8:75-81). This peptide, RTLDKVLEV, is derived from KIAA0020, a gene of unknown function located on chromosome 9. Polymorphic alleles of KIAA0020 encode the alternative sequences PTLDKVLEV and PTLDKVLEL. Genotypic analysis demonstrated that the HA-8-specific cytotoxic T lymphocyte (CTL) clone SKH-13 recognized only cells that expressed the allele encoding R at P1. However, when PTLDKVLEV was pulsed onto cells, or when a minigene encoding this sequence was used to artificially translocate this peptide into the endoplasmic reticulum, it was recognized by CTLs nearly as well as RTLDKVLEV. This indicates that the failure of CTLs to recognize cells expressing the PTLDKVLEV-encoding allele of KIAA0020 is due to a failure of this peptide to be appropriately proteolyzed or transported. Consistent with the latter possibility, PTLDKVLEV and its longer precursors were transported poorly compared with RTLDKVLEV by transporter associated with antigen processing (TAP). These studies identify a new human mHAg and provide the first evidence that minor histocompatibility differences can result from the altered processing of potential antigens rather than differences in interaction with the relevant major histocompatibility complex molecule or T cell receptor.

Impaired assembly yet normal trafficking of MHC class I molecules in Tapasin mutant mice.

Loading of peptides onto major histocompatibility complex class I molecules involves a multifactorial complex that includes tapasin (TPN), a membrane protein that tethers empty class I glycoproteins to the transporter associated with antigen processing. To evaluate the in vivo role of TPN, we have generated Tpn mutant mice. In these animals, most class I molecules exit the endoplasmic reticulum (ER) in the absence of stably bound peptides. Consequently, mutant animals have defects in class I cell surface expression, antigen presentation, CD8+ T cell development, and immune responses. These findings reveal a critical role of TPN for ER retention of empty class I molecules. Tpn mutant animals should prove useful for studies on alternative antigen-processing pathways that involve post-ER peptide loading.

Specific binding of glucosaminylmuramyl peptides to histones.

Intracellular N-acetylglucosaminylmuramyl peptide-binding proteins of murine macrophages and myelomonocytic WEHI-3 cells were characterized. SDS-PAGE and Western blotting revealed proteins with molecular masses of 18, 32 and 34 kDa retaining the ability to specifically bind glucosaminylmuramyl dipeptide. The inhibition analysis demonstrated that only biologically active muramyl peptides but not inactive analogs or fragments of glucosaminylmuramyl dipeptide could inhibit glucosaminylmuramyl dipeptide-binding to these proteins. Purification of these proteins and sequencing of peptides obtained after in-gel trypsin digestion enabled us to identify the above mentioned proteins as histones H1 and H3. These findings suggest that nuclear histones might be target molecules for muramyl peptides.

[Cytogenetic effects in adolescent children from various regions of the Kemerovskaia district]. / Tsitogeneticheskie éffekty u detei-podrostkov iz raznykh raionov Kemerovskoi oblasti.

Considerable variations in the frequency of spontaneous chromosomal aberrations were revealed during a cytogenetic study of two groups of adolescents from ecologically different areas of Kemerovskaya oblast'. In a sample of adolescents living in an industrial center (the Kemerovo city), this parameter (1.4 +/- 0.37%) did not exceed the population average value, whereas adolescents of the same age from a mountain region with sparse industry (the town of Tashtagol) exhibited, on average, a frequency of 5.87 +/- 0.62%. An increased proportion of chromosomal-type aberrations in the qualitative spectrum of cytogenetic damage, which was observed for the group of adolescents from Tashtagol, suggests that this population was exposed to radiation.

[Cloning fragments of cDNA coding variable segments of light and heavy chains of monoclonal antibodies against human interleukin-2]. / Klonirovanie fragmentov kDNK, kodiruiushchikh variabl'nye uchastki legkoi i tiazheloi tsepei monoklonal'nogo antitela protiv interleikina-2 cheloveka.

DNA fragments coding for the variable fragments of the heavy and light chains of the immunoglobulin G1 against human recombinant interleukin-2 were produced using reverse transcription of the total RNA isolated from the murine hybrid myeloma cell line LNKB-2 followed by amplification of the RNA-DNA duplexes with degenerated primers. The fragments obtained were cloned into the plasmid pGEM7-Zf(+) and their structures were determined. The fragments cloned were proved to encode the Fv-fragments by sequencing N-termini of the light and heavy chains of the antibody.

[Polypeptides from murine peritoneal macrophages recognizing glycosaminylmuramoyl dipeptide]. / Polipeptidy iz peritoneal'nykh makrofagov myshi, uznaiushchikh gliukozaminilmuramoildipeptidy.

By means of radioligand analysis, murine peritoneal macrophages were shown to express several hundreds cell surface high-affinity GMDP-binding sites with a binding constant 350 pM. Photoaffinity labeling followed by SDS-PAGE enabled us to identify inside these cells 32-34 and 38 kDa proteins, specifically binding GMDP. Proteins 32-34 kDa were also detected by Western blotting analysis using biotinylated conjugate of polyacrylamide with immobilized GMDP-Lys [(GMDP-Lys)-PAA-(Bi)] in cell lysate of murine peritoneal macrophages.

Production and characterization of monoclonal anti-idiotypic antibodies to muramylpeptide.

Hybridomas producing monoclonal anti-idiotypic antibodies (anti-id MAbs) to N-acetylglucosaminyl-beta 1-4-N-acetylmuramyl-alanyl-D-isoglutamine (GMDP) were developed. Three clones of hybridomas demonstrated the properties characteristic for the Ab2 beta type of anti-id antibody: they bound to Fab-fragments of high-affinity MAb to GMDP; dose-dependent inhibition of this binding by GMDP was observed; immunization of mice with these MAbs resulted in production of GMDP-specific antibodies. When these antibodies were used to stain blots from SDS-PAGE of macrophage lysate, the same receptor proteins were specifically stained as upon staining with 125I-labelled GMDP derivative.

Biochemical characterization of glucosaminylmuramyldipeptide binding sites of murine macrophages.

By using radioligand analysis, murine peritoneal macrophages were shown to express several hundred high-affinity cell surface GMDP-binding sites (Ka 350 pM). Photoaffinity labeling followed by SDS-PAGE enabled us to identify 32-34 and 38 kDa proteins inside these cells that bound GMDP specifically.

Muramyl peptide-binding sites are located inside target cells.

Using flow cytometry and fluorescence polarization analysis, specific muramyl peptide-binding sites were shown to be located inside T-lymphocytes, macrophages and neuroblastoma cells, but not inside B-cells. No binding sites were found on the cell surface. The number of binding sites for each cell type was determined. Two types of binding sites were observed for myelomonocytic WEHI-3 cells with Kd values of 21 and 540 nM. Inhibition analysis demonstrated that for effective binding, an intact glycopeptide molecule and D-configuration of isoglutamine residue are important.

[Characteristics of blood flow in the gastric mucosa in relation to its structure and function in patients with peptic ulcer]. / Osobennosti krovotoka v slizistoi obolochke zheludka v soposta- vlenii s ee strukturoi i funktsiei u bol'nykh iazvennoi bolezn'iu.

Hydrogen clearance was used to assess blood flow in fundal and antral gastric mucosa as well as in the lobule of the auricle in 127 patients with ulcer (99 duodenal and 28 gastric ulcer cases), 34 patients with gastric, duodenal, pancreatic and biliary ++non-ulcer lesions against 20 healthy subjects. The findings underwent analysis in relation to the disease form and phase, baseline characteristics of the mucosa (morphological, functional and bacteriological) and changes in them in response to pentagastrin (6 micrograms/kg), alupent (0.0075 mg/kg), clofelin (0.0015 mg/kg) administration. For ulcer involving the body of the stomach and sutured perforated duodenal ulcer, fundal and antral mucosa blood flow showed a decrease by 1/3, the lowest values presenting in the active disease phase. Diminution in gastric mucosa blood flow correlated with gravity of its gastritic lesion and was not directly related to its Campylobacter contamination. Pentagastrin stimulated blood flow in fundic mucosa and led to its 30% increase whereas the flow intensity remained unaffected in the antral mucosa and skin (lobule of the auricle). Acid production in response to pentagastrin introduction rose 3.5-fold, pepsin 2.1-fold. Alupent and clofelin do not affect blood flow causing a 30-50% increase and decrease in acid and pepsin production, respectively. Separate neurohumoral regulation of gastric mucosa blood flow and secretory activity of the latter permits differential correction of each of the impaired functions.