bluuebunny/crossref_metadata_2025 huggingface dataset:
Сost-effectiveness of preventing cardiovascular death and achieving the target indicator "Reduction of the cardiovascular mortality of the population" of the State Program "Health Development" when using valsartan+sacubitril, dapagliflozin and empagliflozin in patients with heart failure with reduced ejection fraction
Authors: Zhuravleva M. V. , Tereshchenko S. N. , Zhirov I. V. , Nedogoda S. V. , Gagarina Yu. V. , Shabalina E. A.
Published: April 2023

Aim. To evaluate the cost-effectiveness of achieving the target indicator "Reduction of the cardiovascular mortality of the population" of the State Program "Health Development" when using drugs valsartan+sacubitril, dapagliflozin and empagliflozin in patients with New York Heart Association (NYHA) class II-IV heart failure with reduced ejection fraction ≤40% s in 2023-2024.

Material and methods. The target population was Russian patients who received preferential medicines in the last two years after an acute cardiovascular disease. The population size was determined on the basis of Russian literary and statistical sources. To predict the cardiovascular death, a parametric modeling method was used based on published data from clinical trials. The amount of drug costs required to prevent one cardiovascular death, as well as to achieve a one target for reducing cardiovascular mortality, was calculated using each of the comparator drugs in the whole country and separately in each region.

Results. The cost of drugs for the 1st year of therapy to prevent one cardiovascular death in the case of valsartan+sacubitril was RUB 3,99 million, dapagliflozin — RUB 2,63 million, empagliflozin — RUB 4,43 million. There were following costs required to achieve one target indicator for reducing cardiovascular mortality of the State Program "Health Development" for valsartan+sacubitril, dapagliflozin and empagliflozin:

in 2023 — RUB 2197,9 million, RUB 1451,5 million and RUB 2435,9 million, respectively;

in 2024 — RUB 627,4 million, RUB 407,7 million and RUB 706,9 million, respectively.

Conclusion. Among the agents considered, dapagliflozin seems to be the most cost effective for preventing one cardiovascular death and achieving one of the target "Reduction of the cardiovascular mortality" of the State Program "Health Development" in 2023-2024.
Chronotherapy of hypertension: current state of the problem and prospects
Authors: Kobalava Zh. D. , Troitskaya E. A.
Published: April 2023

Chronotherapy for hypertension has been a topic of debate over the past decade. A number of studies up to 2019 suggested that prescribing drugs in the evening has advantages compared to morning, both in terms of normalization of blood pressure and its circadian rhythm, as well as in terms of the risk of adverse outcomes. Some of these studies were not designed for such an analysis, and some have significant limitations that make their interpretation difficult. The results of the HARMONY and TIME studies published in the last 2 years did not confirm any advantage of taking drugs in the evening compared to the morning, but showed its safety. Selection of antihypertensive therapy should be guided by antihypertensive efficacy, duration and stability of the effect, as well as medical adherence. Therefore, a single intake of double or triple fixed-dose combination of long-acting agents at hours convenient for the patient is optimal.
Pericarditis. Clinical Guidelines 2022
Authors: Arutyunov G. P. , Paleev F. N. , Tarlovskaya E. I. , Moiseeva O. M. , Arutyunov A. G. , Koziolova N. A. , Chesnikova A. I. , Rebrov A. P. , Shaposhnik I. I. , Petrova M. M. , Grigorieva N. Yu. , Fomin I. V. , Orlova Ya. A. , Malchikova S. V. , Koroleva L. Yu. , Nosov V. P. , Ayvazyan S. A. , Zairatyants O. V. , Sinitsyn V. E. , Vasyuk Yu. A. , Gendlin G. E. , Dragunov D. O. , Sokolova A. V. , Irtyuga O. B.
Published: April 2023

Russian Society of Cardiology (RSC)

With the participation of the Eurasian Association of Therapists, the Russian Scientific Medical Society of Therapists (RNMOT), the Russian Society of Pathologists, the Russian Society of Radiologists and Radiologists (RSR)

Approved by the Scientific and Practical Council of the Russian Ministry of Health (30.09.2022)
Tuberous Sclerosis Complex Kidney Lesion Pathogenesis: A Developmental Perspective
Authors: Pietrobon Adam , Stanford William L.
Published: April 2023

The phenotypic diversity of tuberous sclerosis complex (TSC) kidney pathology is enigmatic. Despite a well-established monogenic etiology, an incomplete understanding of lesion pathogenesis persists. In this review, we explore the question: How do TSC kidney lesions arise? We appraise literature findings in the context of mutational timing and cell-of-origin. Through a developmental lens, we integrate the critical results from clinical studies, human specimens, and genetic animal models. We also review novel insights gleaned from emerging organoid and single-cell sequencing technologies. We present a new model of pathogenesis which posits a phenotypic continuum, whereby lesions arise by mutagenesis during development from variably timed second-hit events. This model can serve as a conceptual framework for testing hypotheses of TSC lesion pathogenesis, both in the kidney and in other affected tissues.
Green Infrastructure and Healthy Cities: proposal for a Linear Park for the city of Itapuranga, Goiás (Brazil)
Authors: Souza Josimar dos Reis de , Santos Andressa Rodrigues , Reis Laís Naiara Gonçalves dos
Published: April 2023

The instrument called Parque Linear must be, a priori, understood as an important sustainable measure for the use and occupation of urban green areas, in the environmental, social, economic and cultural spheres. These areas, within the Brazilian jurisdiction, are considered by the environmental legislation as Areas of Permanent Preservation (APP), that is, there are a series of prohibitions of constructions and so on. But they are characterized as residual spaces of the remaining natural landscape (when existing) and are, for the most part, invaded and degraded by the urbanization model adopted until today. Due to these problems, many cities in the world and in Brazil have sought to insert this type of park as a measure to mitigate the degraded state in which water courses in urban areas are found, with the aim of improving the quality of life of the population. Thus, this work aims to discuss and demonstrate the relevance of this theme, based on the proposition of Parque Linear in the urban area of Itapuranga, Goiás (Brazil), in the light of the movement for the construction of Healthy Cities, which aims to improve the quality of urban life. As a methodology, bibliographical research, cartographic production, field visit and dialogue with city residents were carried out. The results showed the possibility of installing a linear park adjacent to the GO-230 highway, which cuts through the urban area of the city (urbanized highway), taking advantage of the green areas already present in the stretch, which surround the Tamborim river. In addition, they provided demonstration of the importance of installing this type of instrument to promote the quality of urban life.
The importance of Urban Afforestation: analysis from the mapping of Syzygium malaccense and Licania tomentosa species in the urban area of Itapuranga, Goiás (Brazil)
Authors: Souza Josimar dos Reis de , Silva Samara Cristina Azevedo , Reis Laís Naiara Gonçalves dos
Published: April 2023

The present work aimed to carry out a rereading of the work entitled “Survey of urban afforestation and evaluation of the environmental perception of the inhabitants of the city of Itapuranga-GO”, carried out by Rosilane de Faria and Valéria de Sousa, in 2012. the same areas that were mapped in 2012 were compared and evaluated, focusing on two species commonly seen on city sidewalks: Syzygium malaccense and Licania tomentosa, known as Oiti and Jambota; as well as a survey of the number of existing individuals was carried out. In addition, the existence of patterns was verified in the houses where the cataloged trees were found, given the fact that economic disparity is a factor in the formation of unequal spaces. The specimens located were georeferenced using a GNSS navigation device, model GarminEtrex Vista, and photographed in field work. Subsequently, a database was created in the laboratory with basic information to identify the individual: geographic coordinates, sector, street name, species height, scientific and popular name. As a result, the relevance of some tree species for the purpose of urban afforestation is discussed, in the same way that others are classified as not recommended. During the field incursions, a total of 954 individuals were catalogued, unevenly and disproportionately divided among the four surveyed sectors, considering that the trees found in squares and other areas were not computed. Finally, it was concluded that, contrary to expectations, the areas with the most trees are not the newest areas with the highest purchasing power, but the oldest sectors of the city, with a lower income population.
Covid-19's lessons for standard building design: Proinfância daycare centers
Authors: Fontes Andréa dos Reis , Imbronito Maria Isabel
Published: April 2023

The Covid-19 pandemic brought changes in the behavior of society, with the suspension of several activities, among them the access of children to schools. This study has as main objective the analysis of the daycare spaces of the Proinfância program regarding the attendance of environmental comfort, dimensioning and salubrity, considering the set of issues brought by the pandemic. To achieve this purpose, analyses were made of the type C Proinfância building, project used in the construction of the school unit chosen as case study: the Unidade Municipal de Educação Infantil Profª Júlia Maria de Almeida Oliveira, in the city of Lagarto, Sergipe. The secondary objectives are: to analyze the specificities of the implementation of this standard building in Lagarto and to analyze the post-occupancy condition during and after the Covid-19 pandemic. The methodological approach of the study is quali-qualitative type, applied on documents provided by the Proinfância website and complemented by case study, with detailing of techniques and procedures to achieve the proposed objectives. The study explores the POE methodology (Post-Occupancy Evaluation) for the object of study, selecting the universe of tools to be applied. These are: walkthrough analysis, study of recommendations and technical analysis by the researcher.
Formation of a maneuverable fund with the use of assembled structures
Authors: Guzhova Oksana A. , Didkovskaya Olga V. , Khairullin Marsel F.
Published: April 2023

The article outlines the need to improve the system for the formation of a maneuverable fund. The purpose of the study is formulated to improve the provisions of the mechanism for the formation of a maneuverable housing stock in Russia based on the use of prefabricated structures. The features of the construction of flexible housing using modular structures are considered. Examples of their use in world practice, theoretical and methodological provisions for the formation of a maneuverable fund are presented. A block diagram has been developed for the formation and provision of an additional volume of the maneuverable fund to the municipality based on the use of prefabricated structures.
Manganese: benefit or harm? (overview)
Authors: Kichigin Viktor I.
Published: April 2023

It has been shown that manganese (Mn) is an essential trace element for all life on Earth. Excess or deficiency of this nutrient from the norm leads to severe diseases of plants, animals and humans. It has been established that so far there is no single point of view on the permissible content of Mn in drinking water. It varies from 0.05 mg/dm3 in Europe to 0.4 mg/dm3 in Singapore. The World Health Organization (WHO) recommends the maximum permissible concentration of manganese in drinking water at 0.5 mg/dm3, and the desired concentration is 0.1 mg/dm3. In groundwater, a multiple excess of drinking water standards is typical, especially in the waters of Western Siberia and the northern regions of the European part of the Russian Federation. Thus, in groundwater not associated with Mn deposits, its content can reach 4 mg/dm3, associated with deposits above 300 mg/dm3. In surface waters manganese concentrations up to 8 mg/dm3 are observed. In river waters, the manganese content usually ranges from 0.001 to 0.160 mg/dm3.
Development and justification of the technology of sorption post-treatment of industrial wastewater
Authors: Panfilova Olga N. , Stepanov Sergey V.
Published: April 2023

The technology for the production of sorbents based on clays has been developed, the design parameters of the process, the schematic diagram and the calculation method of the process of sorption post-treatment of wastewater on the example of galvanic production have been given, a technical and economic comparison of options for the construction of wastewater treatment facilities of galvanic production has been carried out.
Using granuated buckwheat husks in urban surface runoff treatment
Authors: Samodolova Olesya A. , Ulrikh Dmitrii V. , Lonzinger Tatiana M.
Published: April 2023

In recent years, the Russian Federation has paid more attention to protecting the environment from the negative impact of various pollutants. The goal of the Closed Loop Economy federal project, for example, was to stimulate the use of recyclable material. The agro-industrial complex produces a huge amount of waste during the processing of crops. One of these wastes is buckwheat husk. There are a number of studies proving the application of buckwheat husks in large quantities as a sorbent for certain wastewater treatment methods. However, the low strength of husk leads to a number of technological difficulties in operation.

The goal of this study is to increase the performance of buckwheat husks through granulation and evaluate the sorption capacity of granulated buckwheat husks when treating urban surface runoff. In this study we used granulated buckwheat husks produced in a method analogous to fuel pellets. Tests were run on real runoff collected from storm sewers in Chelyabinsk. We determined that granulated buckwheat husks effectively remove pollutants from runoff.

In static conditions at a temperature of 10C to 20C, aluminum was most effectively sorbed upon contact with the sorbate over 168 hours (94.12%). At 0C, slightly less aluminum was sorbed (82.35%). Cobalt, chromium, copper, and zinc are completely extracted from runoff after 3 hours of sorption, regardless of temperature changes.In dynamic test conditions, we determined that the buckwheat husk granules totally extract heavy metals (cobalt, chromium, copper) from storm drain runoff. The concentration of aluminum cations was reduced to 68%. Lower concentrations of sodium and silicon cations were also noted.
Building an algorithm for calculation of distances between overground gas pipeline supports of different diameters depending on climatic characteristics
Authors: Balandina Olga A. , Filatova Elena B. , Puring Svetlana M. , Filatova Alena I.
Published: April 2023

The use of averaged norms in the process of performing engineering calculations of gas distribution systems significantly reduces the design time, but does not take into account the influence of climatic operating conditions of linear sections of the aboveground gas network. The paper considers the possibility of using a tabular model of the algorithm for determining the distances between the supports of aboveground gas pipelines of various diameters depending on climatic characteristics on the example of the Samara region. Examples of visualization of the information structure of computational algorithms by means of spreadsheets are given. A block diagram of an algorithm for calculating the values of average spans between aboveground gas pipeline supports for various climatic conditions is proposed. The advantages of using the proposed tabular modeling technique in engineering calculations of gas distribution systems are shown.
Research of technical characteristics of glass-fiber concrete
Authors: Kondratyeva Nadezhda V. , Golovatyuk Mariia A.
Published: April 2023

The article examines the technical characteristics of glass fiber reinforced concrete based on experimental research and selection of the optimal composition of fiber reinforced concrete. When selecting the composition, various technologies for introducing fibers, the percentage of fibers introduced, and the characteristics of the sand used were analyzed. The obtained research results allow us to determine the effectiveness of the use of glass fiber reinforced concrete structures in the reconstruction of buildings and structures. In the manufacture of test samples, materials of domestic production were used.
Conceptual foundations of the post-industrial city
Authors: Danilova Elina V. , Valshin Rasim M.
Published: April 2023

The article is devoted to urban concepts eco-city, creative city, smart city which underlie the development of the city in the post-industrial era. The historical prerequisites for the formation of concepts are considered. The origins of each concept, which were formulated by sociologists, economists and urbanists, are analyzed. The principles of ecological urbanism, a creative city and the main characteristics of a smart city are described. A comparative analysis of the principles of each city is carried out, and general provisions are identified that are present in each of the described urban concepts. In conclusion, a description is given of the image of a post-industrial city, which is alternative to an industrial city.
“Circumbaltian space”: historical background and theoretical and methodological foundations of delimitation
Authors: Monastyrskaya Marina Y.
Published: April 2023

The Circumbaltian Space is presented in the work as the core of the peripheral local civilization of Europe the Baltic Sea civilization, which has become the natural and social basis for the formation of the modern Baltic region. Regional borders are marked in accordance with current scientific and practical approaches to the delimitation of spaces and habitats: natural science, program-strategic and socio-humanitarian. It is shown that the dominant factor in the formation, development and spread of civilizational and, consequently, regioncreating processes in the Baltic Sea has been, since the turn of the VII VIII centuries and retaining its importance today, the urbanization of Primorye. In order to identify, construct, characterize and formalize the genetic code of the latter, a working definition of Circumbaltics is proposed as an objective reality or physical entity, which in physical and geographical terms is a geotory (geospatial form). On the basis of the geotorial concept and the geospatial model of the core of the Baltic Sea civilization the centripetal focus of the region the methodology is substantiated and the method of its delimitation is developed in the context of solving the problems of historical and urban planning research. It is suggested that the genetic code of the Baltic urbanization, the indicators of which are the patterns and specifics of the spatial organization of the Primorsky urbanized settlement system, can serve as the basis for regional identification and/or reidentification of urban development activities carried out within the boundaries of the Northwestern Federal District of the Russian Federation, the European part of Russia as a whole, and thereby contribute to its improvement.
Question of creating the historical center of Togliatti: psychological prerequisites and project practice of preserving the memory of a place
Authors: Solodilov Mikhail V. , Ivanova Anastasiya A.
Published: April 2023

The purpose of the article is to raise the question of the feasibility of creating the historical center of the city of Togliatti in the structure of the Central District on the basis of a new building and transferred from the territory of the flooded Stavropol in the mid-50s. This idea was repeatedly raised at the administrative level and was partly expressed in the projects for the reconstruction of the Central Park, the Museum Quarter and a number of other project proposals. The issue of determining the urban centers of all districts of Togliatti is still being discussed and is debatable, on which there is no consensus. It is proposed to carry out an audit of the preserved historical and architectural heritage, to identify the optimal territory of the historical center with a subsequent design proposal for its improvement. All this leads to the search for conceptual foundations, because the historical heritage of the city with a centuries-old history is almost lost. Architectural methods of preserving the memory of place come to the rescue: commemoration, reminiscence, retrospection, reconstruction. Another task of the study is to combine design practices with psychological techniques aimed at maintaining a stable psycho-emotional state of a person.
Atrium spaces of highly urbanized multifunctional units of urban structure
Authors: Kolesnikov Sergey A. , Medvedeva Nataliia Y.
Published: April 2023

The paper actualizes the concept of the atrium space of a building in the context of the development of modern highly urbanized multifunctional architecture. A retrospective analysis of the development of typological characteristics of atrium spaces in architectural structures from ancient civilizations to the present day is proposed. The hypothesis of an integral connection of the atrium with the concept of multifunctionality of an architectural object is put forward. The factors influencing the evolution of atrium spaces are proposed. Functional components of atrium spaces of modern multifunctional architecture are considered: organization of entrance zones, provision of microclimate in the building, communication and communicative function.
Protomuseum – immersion – proto-spectactor. Visual nature of immersivity. Spatial and sensual experience
Authors: Shlienkova Elena V. , Kaygorodova Khristina V.
Published: April 2023

The article is devoted to the study of the immersiveness of proto-museum and museum environments in a historical context: from proto-interfaces (rock paintings, frescoes, hunting pseudo-targets) to meta-visualization (new media and a museum without walls, tangible objects broadcasting intangible values). The basis of the studied typology of museumified environments are: pre-museum collections (Primitive society / protomuseum, Ancient world / protomuseum-temple / treasury, Middle Ages / protomuseum-theatre). The methodological basis of the study is the analysis of strategies for organizing space and information, which are the main marker of the evolution of the sensual and epistemological nature of man. Based on the prevailing visual practices, the concepts are derived: The Place protomuseum, The Time protomuseum, The Thing protomuseum and, accordingly, scenarios of immersiveness in these environments: immersion bodily (autosuggestion) and speculative (apperception).
Process of adapting international concepts of sustainable construction in Russia
Authors: Rynkovskaya Marina I. , Tcurin Egor D.
Published: April 2023

This article discusses the process of adapting international concepts of sustainable construction in Russia. A review of green standards and an ecological approach to design within the framework of the Russian construction industry has been made. A comparative analysis of Russian and foreign software was made using the example of Renga, ModelStudioCS and Revit in the context of solving problems of sustainable design. The initial experimental stage of adaptation of ecological construction in Russia was identified and the relationship between legal documents, regional conditions for the use of green solutions in construction and the capabilities of Russian software systems was given. A comparative analysis showed the low readiness of Russian computer-aided design programs to solve specific problems of analyzing the energy efficiency of buildings, lighting, acoustics and construction waste.
Hereditary lung diseases and modern possibilities of genetic testing
Authors: Avdeev S. N. , Kondratyeva E. I. , Namazova-Baranova L. S. , Kutsev S. I.
Published: April 2023

The European Respiratory Society website gives the following criterion for the disease to be classified as rare (orphan) - the disease occurs in 1 person per 2 000. One of the well-studied rare lung diseases is cystic fibrosis (CF), which is often considered a medical care model for patients with other orphan diseases. However, effective diagnostics and therapies have not yet been developed for many other rare diseases. Moreover, their true prevalence remains unknown because these diseases often go undiagnosed. One of the problems in diagnosing rare diseases is the lack of knowledge among physicians.

The aim of this review is to provide a brief clinical and genetic description of rare hereditary lung diseases and to show modern genetic diagnostics to raise awareness among physicians. Data from 95 articles on hereditary lung diseases were used.

Results. The results of the analysis of lung diseases associated with bronchiectasis, fibrosis, pneumothorax, and hereditary storage diseases are presented. Genetics and diagnostics, including the three-step molecular genetic testing for cystic fibrosis, are considered in detail. The diagnosis has been developed for both neonatal screening and clinical manifestations. The emergence of targeted therapy based on genetic diagnosis makes neonatal screening even more relevant and leads to an increase in life expectancy. A patient registry was established within 10 years. A detailed analysis of the diagnosis of primary ciliary dyskinesia (PCD) is given, taking into account the absence of a single “golden” standard for the diagnosis of PCD. The genetic basis of the most common hereditary diseases and modern possibilities of their diagnosis are discussed, including sequencing of genes responsible for the development of orphan diseases using standard Sanger sequencing methods and next-generation sequencing, and creating multigene panels.

Conclusion. New molecular diagnostic methods will help to understand the nature of orphan lung diseases, study their epidemiology, and develop new diagnostic algorithms. The study of the genetic causes of rare diseases may serve as a basis for the development of targeted therapy.
Russian registry of patients with cystic fibrosis: lessons and perspectives
Authors: Kondratyeva E. I. , Voronkova A. Yu. , Kashirskaya N. Yu. , Krasovsky S. A. , Starinova M. A. , Amelina E. L. , Avdeev S. N. , Kutsev S. I.
Published: April 2023

A registry of patients with cystic fibrosis (CF) of the Russian Federation has been compiled annually since 2011. Analysis of the national registry with large amounts of clinical and laboratory data helps understand changes in demographic indicators, plan measures to improve the quality of medical care and evaluate their effectiveness.

Aim. To analyze health status of patients with cystic fibrosis in the Russian Federation and the dynamics of key clinical and laboratory parameters from 2011 to 2021. Methods. The health status of CF patients was assessed using the registry data from 2011 to 2021.

Results. The analysis revealed an increase in the total number of patients from 1,026% in 2011 to 3,969 in 2021, in the number of patients identified by neonatal screening from 28.8% to 53.5%, and in coverage by genetic testing from 91.8 to 93.6%. At the same time, the number of mutations detected dropped from 80 to 90.5% and the number of patients with unidentified mutations decreased from 9.5 to 3.2%. The mean age at diagnosis of cystic fibrosis did not change (3.3 ± 5.5 in 2011 and 3.1 ± 6.2 in 2021) despite an increase in the number of patients diagnosed through neonatal screening. There was a difference in M ± SD age from 2011 to 2021 (11.5 ± 8.9 in 2011 and 14 ± 9.8 in 2021). The proportion of adult patients was 24.95% in 2011 and 27.4% in 2021. The therapy changed over 11 years - the number of courses of intravenous therapy decreased from 70.9 to 36.4%, the number of patients using inhaled antipseudomonal therapy expanded to 45%, the number of patients using hypertonic sodium chloride solution expanded from 8.7 to 70.7%, the use of glucocorticoids decreased. The targeted therapy was introduced in 2018, and the number of patients receiving pathogenetic drugs is growing.

Conclusion. The observed changes are indicative of the health status of Russian patients with cystic fibrosis. Analysis of registries helps improve the organization of medical care, predict and implement sanitary and epidemic measures, plan therapy, and assist the regions in organizing outpatient monitoring and microbiological control. The registry is analyzed to organize health care for adult patients.
Function of ion channels of epithelial cells in cystic fibrosis
Authors: Melyanovskaya Yu. L. , Kondratyeva E. I. , Budaeva A. M.
Published: April 2023

Cystic fibrosis is a systemic hereditary disease caused by mutations in the CFTR gene, which regulates the transport of electrolytes (mainly chloride) across the membranes of the epithelial cells that line excretory ducts of exocrine glands. Dysfunction of the CFTR protein reduces passage of chloride ions through cell membranes and disrupts the passage of sodium ions, bicarbonate ions, and water.

The aim of the study was to analyze comprehensively functioning of chloride and alternative (sodium and calcium) channels in the epithelium of patients with cystic fibrosis in relation to the age using functional tests in vitro.

Methods. We used data from medical histories of patients with cystic fibrosis and intestinal current measurements.

Results. The function of the calcium channel decreased with age in people without cystic fibrosis and carriers of “severe” genotypes. The function of sodium, chloride, and calcium channels was lower in all age groups of patients with cystic fibrosis compared to controls (p < 0.05). When comparing groups of patients with “severe genotype” and “mild genotype”, statistically significant differences were found in response to forskolin (p < 0.05). Patients with “mild” genotypes had a residual function of the CFTR channel which decreased with age.

Conclusion. For the first time, the functioning of chloride and alternative channels in cystic fibrosis have been described in relation to the age and the genotype of patients.
Efficacy of CFTR modulators in clinical practice (6-month follow-up)
Authors: Kondratyeva E. I. , Odinaeva N. D. , Zhekaite E. K. , Pasnova E. V. , Fatkhullina I. R. , Maksimycheva T. Yu. , Sherman V. D. , Kutsev S. I.
Published: April 2023

Pathogenetic therapy for the treatment of cystic fibrosis (CF) has been developed that modulates the CFTR protein and restores its activity as a chloride channel. This treatment is represented by CFTR modulators for various genotypes covering 85 - 90% of patients with CF.

The aim was to analyze the efficacy of two targeted drugs in patients aged 6 - 18 years with CF in clinical practice during a 6-month follow-up.

Methods. The study was conducted based on the analysis of the database “CF Patient Registry of the Russian Federation” for 2021 - 2022. The study included 178 patients receiving lumacaftor/ivacaftor and 158 patients receiving elexacaftor/tezacaftor/ivacaftor. Respiratory function indicators (FEV1, FVC), sweat test, and anthropometric data were analyzed.

Results. In the group of children treated with lumacaftor/ivacaftor, Me (Q1 - Q3) body weight (kg) increased at 6-month follow-up from 40.0 (28.9 - 48.0) to 44.9 (29.3 - 50.8), p < 0.001, and the height (cm) increased from 156.0 (140.0 - 161.0) to 158.0 (143.0 - 162.0),p < 0.001. Me (Q1 - Q3) FEV1 improved from 63.5 (42.3 - 84.8) to 72.0 (56.9 - 82.4) %,p < 0.045. Sweat test (mmol/l) decreased Me (Q1 - Q3) from 115 (101.0 - 123.0) to 86.5 (79.0 - 103.0), p < 0.001. During therapy with elexacaftor/tezacaftor/ ivacaftor, Me (Q1 - Q3) body weight (kg) increased at 6-month follow-up from 44.4 (36.8 - 50.0) to 49.3 (44.1 - 51.9),p < 0.001, and Me (Q1 -Q3) height (cm) increased from 160.5 (152.3 - 165.1) to 163.0 (155.5 - 166.9),p < 0.001. Me (Q1 - Q3) FVC and FEV1 improved: FVC from 78.5 (60.9 - 91.0) to 90.5 (76.8 - 106.8) %,p < 0.001, FEV1 from 73.5 (60.5 - 82.1) to 95.0 (65.3 - 107.0) %,p < 0.001. Sweat test (mmol/l) decreased from 119 (108 - 126) to 75.5 (65.3 - 88);р < 0.001.

Conclusion. Health status indicators of of children with CF aged 6 - 18 years were analyzed for 6 months of targeted therapy (lumacaftor/ivacaftor and elexacaftor/tezacaftor/ivacaftor). Positive changes were observed in weight, height, respiratory function, and sweat test.
Characteristics of patients with primary ciliary dyskinesia
Authors: Nikolaeva E. D. , Ovsyannikov D. Yu. , Strel’nikova V. A. , Polyakov D. P. , Tronza T. V. , Karpova O. A. , Fatkhullina I. R. , Bragina Е. E. , Shchagina O. A. , Starinova M. A. , Krasovskiy S. А. , Kyian T. A. , Zhekaite E. K.
Published: April 2023

Primary ciliary dyskinesia (PCD) (Online Mendelian Inheritance in Man - OMIM - #242650) is a rare hereditary disease, which is based on a defect in the ultrastructure of the cilia epithelium of the respiratory tract which leads to the motor function disorder. Data about health characteristics of patients with PCD in the Russian Federation are incomplete.

The aim of the study was to investigate the clinical, laboratory, and instrumental characteristics of patients with PCD.

Methods. The data of 90 patients (22 adults (24.4%) and 68 children (75.6%)) from several medical centers were studied. The following methods were used: medical history, spirometry, microbiological examination of the respiratory tract, video microscopic analysis of the functional activity of the nasal mucosa ciliated epithelium, transmission electron microscopy of the ciliated epithelium, and DNA testing.

Results. The median age at diagnosis was 17.0 years for adults and 5.0 years for children. Kartagener syndrome was detected in 23 (27%) people, including 6 (26.0%) adults. Hearing loss was noted in 5 (26.3%) adult patients and 15 (26.8%) children. Light microscopy of the ciliated epithelium was performed in 14 (82.3%) children and 3 (17.7%) adults. In 12 patients, cilia motor activity was not registered at each of the magnifications (x 100, x 400, x 1,000). Transmission electron microscopy showed that absence ofinternal and external dynein handles (51%) and absence of internal dynein handles (17.9%) were the most common disorders. DNA testing was performed in 55 (61.2%) patients: 16 (29.1%) adults and 38 (70.9%) children. The most common genetic variants were found in the DNAH5 and HYDIN genes. Lung function was reduced in both adults and children, but a significant decrease was noted in adult patients. P. aeruginosa predominated in the culture and accounted for 21.3% (intermittent detection in 13.2%, persistent detection in 9%). It has increased resistance to antibiotics.

Conclusion. The results correlate with the European data. Infection caused by P. aeruginosa with the increased resistance to antibiotics was prevalent in patienths with PCD.
Ciliated cell cultures for diagnosis of primary ciliary dyskinesia
Authors: Demchenko A. G. , Smirnikhina S. A.
Published: April 2023

Primary ciliary dyskinesia (PCD) is a hereditary autosomal recessive disease that results in a defect in the ultrastructure of epithelial cilia. To date, there is no single diagnostic test for PCD, so the diagnosis is based on the results of multiple tests, such as DNA diagnostics, assessment of nasal nitric oxide levels, ciliary beat frequency (CBF) in nasal biopsy, ciliary ultrastructure, etc. Diagnosis of PCD can be difficult due to secondary damage to the airway epithelium, leading to undiagnosed or false positive cases.

The aim of this work was to review studies on the cultivation of human nasal epithelial cells and subsequent differentiation into ciliated cells for the diagnosis of PCD.

Conclusion. In vitro ciliogenesis helps to make a correct diagnosis of PCD while avoiding false positives. There are three different methods of ciliogenesis in vitro: the suspension culture method, the ALI culture method, and the organoid culture method. Each method of ciliogenesis has its own advantages and disadvantages. The ALI culture method is the most widely used. It produces a sufficient number of ciliated cells for diagnosis, which can be maintained in culture for a long time. The obtained cultures of nasal epithelial ciliated cells allow to analyze the ultrastructure of cilia, to evaluate CBF and localization of ciliary proteins, which helps in the diagnosis of PCD.
Randu - Osler - Weber disease (or hereditary hemorrhagic teleangectasia) with respiratory involvement
Authors: Mizernitskiy Yu. L. , Shatokha P. A. , Sokolova L. V.
Published: April 2023

Hereditary hemorrhagic telangiectasia (HHT) is a rare autosomal-dominantly inherited disease characterized by various vascular defects, including nosebleeds, dilation of blood vessels (telangiectasias), and arteriovenous malformations (AVMs) in the lungs and other internal organs. Pulmonary AVMs are observed in 15 - 50% of patients with HHT. The disease manifests in childhood, with the severity of clinical manifestations increasing throughout the patient’s life. The eponymous name of Randu - Osler - Weber disease comes from the surnames of the physicians who first described it in the mid-19th century. Despite some progress in understanding its etiology and pathogenesis, treatment tactics remains incomplete.

The aim of this review is to systematize information on the etiology, diagnosis, and treatment of HHT. This review presents the current status of the problem, lists the main diagnostic tests and the principles of pharmacological and surgical treatment.

Conclusion. The polyorganic lesions in HHT require an interdisciplinary approach to the management of these patients both in childhood and in adulthood. With the discovery of the genetic basis of the disease, pathogenetic therapy with humanized monoclonal antibodies seems promising. However, this therapy requires further research.
Description of the clinical picture and assessment of functional activity of the CFTR channel in a patient with a complex allele [S466X; R1070Q]
Authors: Krasnova M. G. , Melianovskaya Yu. L. , Krasovskiy S. A. , Bulatenko N. V. , Efremova A. S. , Bukharova T. B. , Goldshtein D. V.
Published: April 2023

The presence of pathogenic variants in the CFTR gene causes cystic fibrosis (CF) through various molecular mechanisms that affect the formation and functional activity of the CFTR chloride channel. An important factor affecting the phenotypic manifestations of CF and the effectiveness of targeted therapy is the presence of complex alleles with > 2 consecutive mutations per 1 allele, or in the cis position. The influence of complex alleles on the manifestations of CF has not been sufficiently studied globally due to the small number of studies.

The aim of the study was to investigate the influence of the complex allele [S466X; R1070Q] on the phenotypic manifestations of CF and the effectiveness of targeted therapy in a model of intestinal organoids from a patient with [S466X; R1070Q]/CFTRdele2,3 genotype.

Methods. We used medical history data, intestinal current measurement, intestinal organoid method, and forskolin test.

Results. The progressive nature of the disease with a clear degradation of lung function was established. The ICM method showed absent chloride channel function. The tests on the culture of organoids obtained from the intestinal tissue indicated a complete loss of the chloride channel function. In addition, the complex allele [S466X; R1070Q] was insensitive to all targeted drugs tested.

Conclusion. The complex allele [S466X; R1070Q] causes a complete loss of the functional CFTR protein and is not sensitive to any of the approved targeted drugs.
Primary ciliary dyskinesia in a young woman: case report with challenged transition from pediatrics to adult network
Authors: Zinchenko A. V. , Gembitskaya T. E. , Bondarenko I. B.
Published: April 2023

Primary ciliary dyskinesia (PCD) is a rare genetic autosomal recessive disease associated with a defect in the ultrastructure of epithelial cilia. Currently, there is no standard method for diagnosing PCD, so the diagnosis is based on the clinical picture and the results of tests, such as DNA diagnostics, nasal nitric oxide measurements, ciliary beat frequency in a nasal biopsy, ciliary ultrastructure, etc. Diagnosis of PCD can be difficult due to secondary damage to the respiratory epithelium, which often results in undiagnosed or false positive cases. Differential diagnosis with diseases forming widespread bronchiectasis (BE) and upper respiratory tract lesions, especially with cystic fibrosis (CF), is necessary.

The aim of this paper is to introduce the difficulties of diagnosis, the appropriate level of detail of the clinical, laboratory and instrumental characteristics over a long period of time, and the organization of care for a patient with PCD. This article describes a clinical case of PCD in a young woman, diagnosed at the age of 17, presents the difficulties and typical mistakes in the management of such patients, and the lack of succession of pediatrician-pulmonologist care.

Conclusion. The presented clinical case demonstrates how difficult the diagnosis of PCD is. Such patients need a complex examination, a thorough differential diagnosis to exclude other diseases with a similar clinical picture. Long-term follow-up is carried out by a multidisciplinary team with mandatory microbiological monitoring. The organized care for patients should begin in early childhood and continue in adulthood with proper succession of care and follow-up by of pulmonologist, preferably in specialized centers.
A rare variant of primary ciliary dyskinesia in combination with hereditary hemorrhagic telangiectasia type 1: a case from practice
Authors: Shatokha P. A. , Novak A. A. , Shudueva A. R. , Mizernitskiy Yu. L. , Groznova O. S.
Published: April 2023

Primary ciliary dyskinesia (PCD) is a rare genetic disease belonging to the group of ciliopathies. The disease develops because a defect in the ultrastructure of the epithelial cilia in the respiratory tract and similar structures (sperm flagella, villi of the fallopian tubes, ventricular ependyma, etc.) disturbs their motor function. Currently, various clinical and genetic variants of the disease are distinguished, increasing the effectiveness of dynamic examination and treatment.

Aim. In this article, we describe a patient with a rare variant of PCD that we identified in combination with a mutation in the ENG gene responsible for the development of hereditary hemorrhagic telangiectasia type 1 (HHT-1). HHT-1 is a rare hereditary disease that manifests as various vascular dysplasias, including arteriovenous malformations (AVM) in the lungs, which can significantly worsen the course of the disease and be a predictor of an unfavorable outcome.

Conclusion. The presented case demonstrates a combination of two rare genetic diseases in a child. The uniqueness of the case also lies in the fact that the identified rare mutation in the DRC1 gene responsible for the development of PCD is not associated with a loss of motility of the cilia of the ciliated epithelium, which makes the testing and the correct diagnosis even more difficult.
Primary ciliary dyskinesia in a child with type II Simpson -Golabi - Bemel syndrome due to OFD1 gene mutation
Authors: Strelnikova V. A. , Tsverava A. G. , Ovsyannikov D. Yu. , Zhekaite E. K. , Kondakova O. B. , Berejansky P. V. , Savostyanov K. V. , Gorev V. V. , Airapetyan M. I. , Topilin O. G.
Published: April 2023

Primary ciliary dyskinesia (PCD) is an orphan disease associated with mutations in several genes. It is a ciliopathy, an abnormality of the cilia and flagella. Ciliopathies include the extremely rare Simpson - Golabi - Bemel syndrome (SSGB) type II.

The aim of this article is to familiarize the reader with the possibility of simultaneous presence of type II SSGB and PCD in a patient with bronchiectasis (BE).

Results. The first clinical observation in the Russian literature is presented withhistory, physical examination, including clinical and morphologic examination, results of additional investigations and initiation of therapy. The case describes a 15-year-old patient with BE and other lesions typical of PCD confirmed on the basis of structural changes in the cilia of the respiratory epithelium of the trachea detected by transmission electron microscopy. The patient had a pathogenic mutation of the OFD1 gene responsible for the development of both type II SSGB and PCD.

Conclusion. Several variants of ciliopathies may occur in one patient, and PCD may present as a syndrome.
Clinical case of a patient with Prader - Willi syndrome
Authors: Nuralieva G. S. , Kryuchkova K. Yu. , Anokhina V. M. , Bolotskaya A. A. , Kozhevnikova M. M. , Avdeev I. S. , Nekludova G. V. , Gaynitdinova V. V. , Khaziakhmetova M. R. , Avdeev S. N.
Published: April 2023

Prader — Willi syndrome (PWS) is a rate multisystem disease caused by a developmental disorder of the nervous system. The syndrome is associated with an imprinting defect, i.e. lack of expression of paternal genes on chromosome 15 q11.2q13.1. This genetic defect leads to cognitive and behavioral disorders; hypothalamic dysfunction; endocrine, cardiovascular, musculoskeletal, respiratory, and other disorders. PWS is the most frequent cause of hereditary obesity. In turn, the obesity causes the obesity-hypoventilation syndrome and respiratory failure.

The aim of this article was to describe a clinical case of 28-year-old female who presented with acute hypercapnic respiratory failure.

Conclusion. The patient was treated with respiratory support (non-invasive ventilation). The timely diagnosis and treatment of respiratory failure is important for the outcome as it can improve the patient’s quality of life and the life expectancy.
Hypercapnic respiratory failure in a patient with nemaline myopathy
Authors: Chuchalin A. G. , Amirova T. O. , Brodskaya O. N. , Baranova A. V. , Butyugina I. N.
Published: April 2023

Neuromuscular diseases are often associated with a range of respiratory complications, presenting both diagnostic and therapeutic challenges for pulmonologists.

The aim of this article is to discuss search of genetic causes and means of respiratory support in case of a man who was diagnosed with NM after 50 years of age. The selected diagnostic and treatment algorithms allowed for successful control of the patient’s condition for 4 years. Whole exome sequencing identified nemaline myopathy (NM), a rare genetically-determined skeletal muscle pathology. Respiratory failure syndrome is considered a life-threatening condition in NM. The severity and characteristics of the clinical course vary depending on the specific mutations. The typical course of NM is characterized by generalized, slowly progressive myopathy, and the manifestation of respiratory failure may be triggered by comorbidities.

Conclusion. The course and management of respiratory failure in NM are poorly understood. Whole exome sequencing made it possible to establish genetic diagnosis, evaluate prognosis and the contribution of comorbidities to the patient’s condition. Noninvasive ventilation compensated the respiratory failure and resolved the symptoms of right ventricular heart failure.
Bio-photonics in dentistry: A review
Authors: Prasad Vaishnavi , Aeran Himanshu , Tuli Amrinder Singh
Published: April 2023

Biophotonics is the new extended branch of photonics, which is the combination of photonics and biology. It is also known as biomedical optics as it has become an important tool for biomedical diagnosis, therapy, monitoring, imaging, and surgery. This branch deals with action of light on biological mattermainly tissue. Three types of laser-tissue interactions are known based on interaction time and active power density. Photochemical, photothermal, photomechanical and photoionization effects.