[The effect of COVID-19 pandemic on attitude of internet-space surfers to professional activity of physician].

The content-analysis was applied to messages (created in April-May of 2018, 2020, 2021 and 2022) from Internet. The drastic increase of interest of audience to issue of medical care support and professional activity of physicians during period of increasing of morbidity of COVID-19 was established. The changing of basic sites for placement of content notably augmentation of mass media role was noticed. The increase of interest to research issue in audiences older than 60 years and in individuals with secondary special education was established. Furthermore, positive alteration of tonality of messages was noted. In 2018, on one positive message fell two negative messages. Starting from 2020, positive messages prevail over negative messages: 2020 - in two times, 2021 - 2.1 times, 2022 - 4.6 times. In absolute values, the number of messages of positive tonality increased up to 9.8 times in 2022 as compared to 2018. Starting from 2020, in the word cloud appeared words "gratitude" and "thank you".

[Analysis of hearing aids application in elderly patients.]

The aim of the study is to evaluate the possibility to implement machine learning to create a digital auditory profile for elderly patients and to analyze the hearing aid fitting efficacy depending on involvement of the peripheral and central auditory pathways in a pathological process. Data analysis of 375 people aged 60-93 years is presented. 355 patients with chronic bilateral hearing loss (230 of them used hearing aids) were included in the main group, and 20 normal hearing elderly people were included in the control group. Audiological examination consisted of standard tests (pure tone audiometry, impedancemetry, speech audiometry in quiet) and tests to evaluate the central auditory processing (binaural fusion, dichotic digits, speech audiometry in noise, random gap detection). The Montreal Cognitive Assessment was used to detect cognitive impairment. The hearing aid fitting efficiency was evaluated with COSI questionnaire and speech audiometry in free field. Processing of the results was carried out using Pearson's correlation analysis aimed at creating a polynomial model of a patient's hearing on the basis of the limited test battery. There were close correlations between the state of cognitive functions and age, results of tests to evaluate the central auditory processing, as well as patients' satisfaction of hearing aid. The results of the work indicate the possibility of using computer technologies of data analysis to develop rehabilitation programs for elderly hearing impaired patients.

Vancouver call for action to strengthen expertise in radiological protection worldwide.

Ionising radiation has been used for over a century for peaceful purposes, revolutionising health care and promoting well-being through its application in industry, science, and medicine. For almost as long, the International Commission on Radiological Protection (ICRP) has promoted understanding of health and environmental risks of ionising radiation and developed a protection system that enables the safe use of ionising radiation in justified and beneficial practices, providing protection from all sources of radiation. However, we are concerned that a shortage of investment in training, education, research, and infrastructure seen in many sectors and countries may compromise society's ability to properly manage radiation risks, leading to unjustified exposure to or unwarranted fear of radiation, impacting the physical, mental, and social well-being of our peoples. This could unduly limit the potential for research and development in new radiation technologies (healthcare, energy, and the environment) for beneficial purposes. ICRP therefore calls for action to strengthen expertise in radiological protection worldwide through: (1) National governments and funding agencies strengthening resources for radiological protection research allocated by governments and international organisations, (2) National research laboratories and other institutions launching and sustaining long-term research programmes, (3) Universities developing undergraduate and graduate university programmes and making students aware of job opportunities in radiation-related fields, (4) Using plain language when interacting with the public and decision makers about radiological protection, and (5) Fostering general awareness of proper uses of radiation and radiological protection through education and training of information multipliers. The draft call was discussed with international organisations in formal relations with ICRP in October 2022 at the European Radiation Protection Week in Estoril, Portugal, and the final call announced at the 6th International Symposium on the System of Radiological Protection of ICRP in November 2022 in Vancouver, Canada.

[Insulator Protein CP190 Regulates Expression of Spermatocyte Differentiation Genes in Drosophila melanogaster Male Germline].

CP190 protein is one of the key components of Drosophila insulator complexes, and its study is important for understanding the mechanisms of gene regulation during cell differentiation. However, Cp190 mutants die before reaching adulthood, which significantly complicates the study of its functions in imago. To overcome this problem and to investigate the regulatory effects of CP190 in adult tissues development, we have designed a conditional rescue system for Cp190 mutants. Using Cre/loxP-mediated recombination, the rescue construct containing Cp190 coding sequence is effectively eliminated specifically in spermatocytes, allowing us to study the effect of the mutation in male germ cells. Using high-throughput transcriptome analysis we determined the function of CP190 on gene expression in germline cells. Cp190 mutation was found to have opposite effects on tissue-specific genes, which expression is repressed by CP190, and housekeeping genes, that require CP190 for activation. Mutation of Cp190 also promoted expression of a set of spermatocyte differentiation genes that are regulated by tMAC transcriptional complex. Our results indicate that the main function of CP190 in the process of spermatogenesis is the coordination of interactions between differentiation genes and their specific transcriptional activators.

Summary of the 2021 ICRP workshop on the future of radiological protection.

The International Commission on Radiological Protection (ICRP) has embarked on a process to review and revise the current System of Radiological Protection ('the System'). To stimulate discussion, the ICRP published two open-access articles: one on aspects of the System that might require review, and another on research that might improve the scientific foundation of the System. Building on these articles, the ICRP organized a Workshop on the Future of Radiological Protection as an opportunity to engage in the review and revision of the System. This digital workshop took place from 14 October-3 November 2021 and included 20 live-streamed and 43 on-demand presentations. Approximately 1500 individuals from 100 countries participated. Based on the subjects covered by the presentations, this summary is organized into four broad areas: the scientific basis, concepts and application of the System; and the role of the ICRP. Some of the key topics that emerged included the following: classification of radiation-induced effects; adverse outcome pathway methodologies; better understanding of the dose-response relationship; holistic and reasonable approaches to optimization of protection; radiological protection of the environment; ethical basis of the System; clarity, consistency and communication of the System; application of the System in medicine and application of the principles of justification and optimization of protection.

Methods of massive parallel reporter assays for investigation of enhancers.

The correct deployment of genetic programs for development and differentiation relies on finely coordinated regulation of specific gene sets. Genomic regulatory elements play an exceptional role in this process. There are few types of gene regulatory elements, including promoters, enhancers, insulators and silencers. Alterations of gene regulatory elements may cause various pathologies, including cancer, congenital disorders and autoimmune diseases. The development of high-throughput genomic assays has made it possible to significantly accelerate the accumulation of information about the characteristic epigenetic properties of regulatory elements. In combination with high-throughput studies focused on the genome-wide distribution of epigenetic marks, regulatory proteins and the spatial structure of chromatin, this significantly expands the understanding of the principles of epigenetic regulation of genes and allows potential regulatory elements to be searched for in silico. However, common experimental approaches used to study the local characteristics of chromatin have a number of technical limitations that may reduce the reliability of computational identification of genomic regulatory sequences. Taking into account the variability of the functions of epigenetic determinants and complex multicomponent regulation of genomic elements activity, their functional verification is often required. A plethora of methods have been developed to study the functional role of regulatory elements on the genome scale. Common experimental approaches for in silico identification of regulatory elements and their inherent technical limitations will be described. The present review is focused on original high-throughput methods of enhancer activity reporter analysis that are currently used to validate predicted regulatory elements and to perform de novo searches. The methods described allow assessing the functional role of the nucleotide sequence of a regulatory element, to determine its exact boundaries and to assess the influence of the local state of chromatin on the activity of enhancers and gene expression. These approaches have contributed substantially to the understanding of the fundamental principles of gene regulation.

Keeping the ICRP recommendations fit for purpose.

The International Commission on Radiological Protection (ICRP) has embarked on a review and revision of the system of Radiological Protection that will update the 2007 general recommendations in ICRPPublication 103. This is the beginning of a process that will take several years, involving open and transparent engagement with organisations and individuals around the world. While the system is robust and has performed well, it must adapt to address changes in science and society to remain fit for purpose. The aim of this paper is to encourage discussions on which areas of the system might gain the greatest benefit from review, and to initiate collaborative efforts. Increased clarity and consistency are high priorities. The better the system is understood, the more effectively it can be applied, resulting in improved protection and increased harmonisation. Many areas are identified for potential review including: classification of effects, with particular focus on tissue reactions; reformulation of detriment, potentially including non-cancer diseases; re-evaluation of the relationship between detriment and effective dose, and the possibility of defining detriments for males and females of different ages; individual variation in the response to radiation exposure; heritable effects; and effects and risks in non-human biota and ecosystems. Some of the basic concepts are also being considered, including the framework for bringing together protection of people and the environment, incremental improvements to the fundamental principles of justification and optimisation, a broader approach to protection of individuals, and clarification of the exposure situations introduced in 2007. In addition, ICRP is considering identifying where explicit incorporation of the ethical basis of the system would be beneficial, how to better reflect the importance of communications and stakeholder involvement, and further advice on education and training. ICRP invites responses on these and other areas relating to the review of the System of Radiological Protection.

Fluorescence imaging of cells using long-range electromagnetic surface waves for excitation.

We present a depth-localized illumination technique for wide-field fluorescence microscopy, based on long-range optical surface waves. This technique allows one to excite the fluorescence only in a thin near-substrate layer of the specimen. Our experimental setup is compatible with both upright and inverted microscopes. It provides fluorescent microscopic images, which are superior to the epifluorescence ones in signal-to-noise ratio, contrast, and detail. We demonstrate the applicability of our technique for imaging both bacterial and eukaryotic cells (E. coli and HeLa, respectively).

The radiological environment at the Mayak PA site and radiation doses to individuals involved in emergency and remediation operations after the 'Kyshtym Accident' in 1957.

This article assesses the radiological environment at the nuclear site of the Mayak PA, Russian Federation, during and after the accident in 1957, the so-called 'Kyshtym Accident', and the radiation doses to those who participated in the eradication of its consequences. Based on numerous archival documents, this paper presents the radiation data for 1957-1960, including individual dosimetry monitoring data and estimated doses to the Mayak workers, as well as the to personnel in supporting organisations and the military involved in the remediation operations. From 1957-1959 some 38 500 individuals took part in the clean-up actions and remediation of contaminated areas of the Mayak PA industrial site after the accident, including individuals exposed at the time of the accident: Mayak PA employees, militarypersonnel, and civil construction workers. External equivalent doses to 10 500 individuals were estimated in the range of 220 to 265 mSv, while there were cases of doses up to 950 mSv and higher. The collective dose received during the accident and its aftermath was in the region of 7300 person-Sv. By October-December 1957, the collective dose was about 4500 person-Sv. Collective doses recorded in 1958 and 1959 amounted to 2250 person-Sv and 480 person-Sv, respectively.

Luminescence dosimetry for evaluation of the external exposure in Metlino, upper Techa River valley, due to the shore of the Metlinsky Pond: A feasibility study.

Luminescence dosimetry was performed using bricks from the former settlement of Metlino, Southern Urals, Russia, to investigate the feasibility of validating the Techa River Dosimetry System (TRDS) 2016 for the shore of the Metlinsky Pond, upper Techa River region. TRDS is a code for estimating external and internal doses for members of the Extended Techa River Cohort. Several brick samples were taken from the north-western wall of the granary, facing the Metlinsky Pond. Samples were measured at different heights and at different depths into the bricks. Dating of the granary was performed by analyzing well shielded bricks. Assessment of the gamma dose-rate at the sample positions was done by thermoluminescent dosimeters and the dose-rate in front of the granary mapped with a dose-rate meter. Anthropogenic doses in bricks vary from 0.8 to 1.7 Gy and show an increase with sampling height. A similar height profile is observed for the current gamma dose-rate, which is compatible with the results of the dose-rate mapping. Implications for validating the TRDS are discussed.

Plutonium production and particles incorporation into the human body.

Plutonium is one of the most toxic radioactive substances known. The isotope 239Pu gained attention when it had become known as a potential explosive material for atomic bombs. This paper describes the main problems encountered during the early years of operation of the first plutonium production plant in the former Soviet Union, the Mayak Production Association (Mayak PA). Mayak PA caused severe radioactive contamination of the environment and exposure personnel and population living in the vicinity areas to high radiation doses. The authors focus on key findings of large-scale studies on the internal dosimetry of workers for use in assessment of radiological risks from exposure to plutonium. This work presents an overview of the important issues for inhalation dose assessments such as generation of plutonium particles, plutonium intake, dissolution of plutonium particles, distribution of plutonium in humans, related exposures and health effects. Understanding the relationship between health effects, radiation dose and route of exposure helps quantify the health risks associated with occupational exposure in the nuclear industry and validate the radiation protection standards used in the Russian Federation and worldwide.

[The participation of religious organizations in formation of population attitude to transplantation of organs and tissues].

The article discusses issue of possibility of influence of religious organizations on the attitude of population to issues of human organ transplantation. The attitude of followers of different religions to key issues of bioethics related to organ donation and transplantation is analyzed. It is concluded that there are no definite prohibitions on implementing this kind of medical intervention in modern religious regulations. The study of results of questionnaire survey of two groups of respondents revealed certain part of population, whose decision on the issues of posthumous organ donation would be influenced by the opinion of representative of religious organization. It is established that every tenth respondent appealed to the Orthodox priest when making decision to sign consent paper concerning posthumous exempt of organ from relatives. It is concluded that it is possible to affect the formation in certain part of population understanding of need to support organ donation and transplantation in case of active work in this direction of representatives of religious organizations.

[The Attitude of Physicians of Donor Bases to Problems of Transplantation of Human Organs and Tissues].

The article considers social aspects of transplantology on the basis of analysis of data of questionnaire survey of 266 physicians of donor bases of the Federal Center implementing transplantation of human organs and tissues. The respondents were representatives of the most prevalent medical professions and ll age gender groups. According to study results, physicians are aware of importance of development of organs and tissues transplantation in the region though take a very passive standing related to informing transplantation specialists about availability of a potential donor. The involvement of physicians in the transplantation program in the first place depends on position of administration of medical institution. At the same time, 44,3±3,1% of physicians are aware of such the most important normative legal principle regulating possibility of postmortem intake of organs as consent presumption. Less than 18,6±2,4% of physicians support this standard. Half of the respondents are ready, in case of their instant death, to become donors of organs and are ready too in case of such a proposal to sign consent to possible postmortem donorship. Therefore, one of conditions of development of organs and tissues transplantation in the region is implementation of explanatory work with medical community targeted to increasing of motivation of personnel of donor bases to active interaction with transplantology specialists.

External dose reconstruction for the former village of Metlino (Techa River, Russia) based on environmental surveys, luminescence measurements, and radiation transport modelling.

In the first years of its operation, the Mayak Production Association, a facility part of the Soviet nuclear weapons program in the Southern Urals, Russia, discharged large amounts of radioactively contaminated effluent into the nearby Techa River, thus exposing the people living at this river to external and internal radiations. The Techa River Cohort is a cohort intensely studied in epidemiology to investigate the correlation between low-dose radiation and health effects on humans. For the individuals in the cohort, the Techa River Dosimetry System describes the accumulated dose in human organs and tissues. In particular, organ doses from external exposure are derived from estimates of dose rate in air on the Techa River banks which were estimated from measurements and Monte Carlo modelling. Individual doses are calculated in accordance with historical records of individuals' residence histories, observational data of typical lifestyles for different age groups, and age-dependent conversion factors from air kerma to organ dose. The work here describes an experimentally independent assessment of the key input parameter of the dosimetry system, the integral air kerma, for the former village of Metlino, upper Techa River region. The aim of this work was thus to validate the Techa River Dosimetry System for the location of Metlino in an independent approach. Dose reconstruction based on dose measurements in bricks from a church tower and Monte Carlo calculations was used to model the historic air kerma accumulated in the time from 1949 to 1956 at the shoreline of the Techa River in Metlino. Main issues are caused by a change in the landscape after the evacuation of the village in 1956. Based on measurements and published information and data, two separate models for the historic pre-evacuation geometry and for the current geometry of Metlino were created. Using both models, a value for the air kerma was reconstructed, which agrees with that obtained in the Techa River Dosimetry System within a factor of two.

Small molecule inhibition of cAMP response element binding protein in human acute myeloid leukemia cells.

The transcription factor CREB (cAMP Response-Element Binding Protein) is overexpressed in the majority of acute myeloid leukemia (AML) patients, and this is associated with a worse prognosis. Previous work revealed that CREB overexpression augmented AML cell growth, while CREB knockdown disrupted key AML cell functions in vitro. In contrast, CREB knockdown had no effect on long-term hematopoietic stem cell activity in mouse transduction/transplantation assays. Together, these studies position CREB as a promising drug target for AML. To test this concept, a small molecule inhibitor of CREB, XX-650-23, was developed. This molecule blocks a critical interaction between CREB and its required co-activator CBP (CREB Binding Protein), leading to disruption of CREB-driven gene expression. Inhibition of CBP-CREB interaction induced apoptosis and cell-cycle arrest in AML cells, and prolonged survival in vivo in mice injected with human AML cells. XX-650-23 had little toxicity on normal human hematopoietic cells and tissues in mice. To understand the mechanism of XX-650-23, we performed RNA-seq, ChIP-seq and Cytometry Time of Flight with human AML cells. Our results demonstrate that small molecule inhibition of CBP-CREB interaction mostly affects apoptotic, cell-cycle and survival pathways, which may represent a novel approach for AML therapy.

A computer simulation study of soft tissue characterization using low-frequency ultrasonic tomography.

We investigate the potential of using ultrasonic diffraction tomography technique for characterization of biological tissues. Unlike most of other studies where ultrasonic tomography operates at frequencies higher than 1 MHz, low-frequency tomography uses lower frequencies on the order of 0.3-0.5 MHz. Such a choice is due to low attenuation at these frequencies, resulting in higher precision of input data. In this paper we explore transmission and reflection schemes for both 2D (layer-by-layer) and 3D tomography. We treat inverse tomography problems as coefficient inverse problems for the wave equation. The time-domain algorithms employed for solving the inverse problem of low-frequency tomography focus on the use of GPU clusters. The results obtained show that a spatial resolution of about 2-3mm can be achieved when operating at the wavelength of about 5mm even using a stationary 3D scheme with a few fixed sources and no rotating elements. The study primarily focuses on determining the performance limits of ultrasonic tomography devices currently designed for breast cancer diagnosis.

Dynamics of body burdens and doses due to internal irradiation from intakes of long-lived radionuclides by residents of Ozyorsk situated near Mayak PA.

This paper presents and discusses new autopsy results and other historic data from earlier autopsies and environmental monitoring linked to releases from the Mayak PA facilities in the Chelyabinsk oblast in the southern Urals. The focus is on residents of the town of Ozyorsk located near to Mayak PA and the dynamics of body burdens and radiation doses from inhalation of plutonium alpha and americium-241, and ingestion of strontium-90 and caesium-137. It is demonstrated that accumulation and exposure from these radionuclides was mainly due to unplanned releases in the 1950s and 60s. The mean content of plutonium alpha at the time of autopsy of people commencing residence in Ozyorsk from 1949 to 1959 was about 3.5 Bq, falling to 0.2 Bq in those arriving after 1990. A reducing trend was also seen for (241)Am. The highest (90)Sr content in Ozyorsk residents was measured in 1967. The (137)Cs body content of residents arriving in Ozyorsk at any time was in almost all cases below the limit of detection. The committed effective dose from internal exposure to these long-lived radionuclides which would have been accumulated in Ozyorsk residents if present from 1949 to 2013 is estimated to be 13 mSv. This dose is primarily attributed to intakes during 1949 to 1959 when the annual effective dose rate was approximately 1 mSv y(-1). The current value is about 0.1 mSv y(-1). This dose is about 20 times higher than the dose from global man-made fallout, which is about 0.005 mSv y(-1) at present, but much lower than that from natural background radiation, i.e. about 2 mSv y(-1). The experience gained from this work and continuing activities can contribute to the development of improved international guidance in legacy situations, particularly as regards the provision and use of monitoring data to test and thereby build confidence in prognostic models for radiation conditions and potential future exposures. The scope includes evidence for the rate of reduction in radionuclide concentrations in environmental media and in their bioavailability, resuspension of long-lived alpha radionuclides, uptake of (90)Sr and (137)Cs in the food-chain, and confirmation of cumulative uptake via autopsy and whole body counting measurements. Continuing investigations will thus support decisions on future planned releases and contribute to planning of remediation of other areas affected by historic releases.

[THE MOTIVATION OF MEDICAL PERSONNEL OF MULTIFIELD HOSPITAL TO WORKING OVER STANDARDS OF SINGLE JOB POSITION].

The article considers results of study concerning prevalence of physicians working over standards of single job position in multifield hospital, including factors motivating to extra job. The research purpose was to analyze impact of gender age structure of medical personnel of multfield public medical organization on motivation of physicians to work over standards of single job position. The objectives consisted of analyzing prevalence of over standard work of medical personnel of multifield public medical organization with consideration of social structure and studying factors motivating physicians to work over standards of single job position. The study was carried out on the basis of questionnaire survey of physicians. The results of study testify higher degree of prevalence of working over standards of single job position in modern health care. So, 64.8 ± 3.6% of respondents work subject to conditions of internal and/or external moonlighting. Moreover; one third of physicians enlisted to extra job. Among physicians males more often than females work subject to conditions of moonlighting, perform extra job, enlist to working during days off. The specialists of age group from 35 to 54 years work subject to conditions of external and internal moonlighting more often than younger physicians. Among physicians, the most significant cause of working subject to conditions of moonlighting is additional earnings. At that, every fifth physician works over standards of job position with purpose to increase one's professional competence. The study results permit concluding that aspects of social structure of modern medical staff significantly impact motivation and hence possibility of enlisting workers to work over standards of single job position.

[THE OPTIMIZATION OF THE ACTIVITY OF ORGANS OF FEDERAL SERVICE FOR SUPERVISION OF CONSUMER RIGHTS PROTECTION AND HUMAN WELFARE IN THE SVERDLOVSK REGION].

In the Sverdlovsk region there have developed and implemented methodological approaches to the optimization oj the activity of the Directorate and the Centre directed to the improvement of the sanitary and epidemiological surveillance and in the sphere of the protection of the rights of consumers in the framework of the development of an comprehensive regional system of risk management for the population's health in the Sverdlovsk region.

[Radiobiological Human Tissue repository: progress and perspectives for solving the problems of radiation safety and health protection of personnel and population].

Radiobiological Human Tissue repository was established in order to obtain and store biological material from Mayak PA workers occupationally exposed to ionizing (α- and/or γ-) radiation in a wide dose range, from the residents exposed to long term radiation due to radiation accidents and transfer of the samples to scientists for the purpose of studying the effects of radiation for people and their offspring. The accumulated biomaterial is the informational and research potential that form the basis for the work of the scientists in different spheres of biology and medicine. The repository comprises 5 sections: tumor and non-tumor tissues obtained in the course of autopsies, biopsies, surgeries, samples of blood and its components, of DNA, induced sputum, saliva, and other from people exposed or unexposed (control) to radiation. The biomaterial is stored in formalin, in paraffin blocks, slides, as well as in the freezers under low temperatures. All the information on the samples and the registrants (medical, dosimetry, demographic, and occupational data) was obtained and entered into the electronic database. A constantly updated website of the repository was developed in order to provide a possibility to get acquainted with the material and proceed with application for biosamples for scientists from Russia and abroad. Some data obtained in the course of scientific research works on the basis of the biomaterial from the Repository are briefly introduced in the review.