Antigenic Components of Chemical Bivalent Cholera Vaccine, Methods of their Isolation and Control

The paper presents a review of the data on the methods of isolation and control of Vibrio cholerae antigens – cholerogen-anatoxin and O-antigens of Inaba and Ogawa – components of the oral bivalent chemical cholera vaccine produced by the RusRAPI “Microbe”, the only prophylactic drug against cholera registered in the territory of the Russian Federation. Currently, the vaccine is produced using the method of segregated manufacturing of cholerogenanatoxin and O-antigens Inaba and Ogawa with step-by-step control of their main properties, which ensures the production of a high-quality finished product. Ultrafiltration is an effective method for concentrating a semi-finished product, which helps to reduce losses and increases the yield of the final product. It remains promising to develop a method for gentle steril ization of O-antigens to maximize the preservation of specific activity. To control the specific activity of the antigenic components and the finished vaccine preparation, a complex of in vivo and in vitro methods is applied. However, the multi-stage process and duration, the use of several types of laboratory animals, as well as modern WHO requirements determine the need for the introduction of alternative in vitro control methods. The use of cell cultures as a replacement for the biological method appears prospective, and demonstrates a positive correlation with animal tests. To assess the activity of antigens, the use of an immunochemical method – dot-immunoassay with gold nanoparticles – is put forward, which will make it possible to harmonize the control method at all stages of the production process, as well as to determine the serovar specificity of Vibrio cholerae O-antigens. The development of molecular-genetic, microbiological, immunochemical methods is relevant for a more complete and comprehensive control of the main immunogens of industrial strains of cholera vibrio. The introduction of promising methods for obtaining antigens and monitoring their properties will allow for a more complete characterization of the component composition of the finished dosage form of the chemical cholera vaccine

Investigating the stability of the Properties of Vibrio cholerae strains – Producers of Active Components of the Chemical Cholera Vaccine

One of the key requirements to producer strains used in the manufacturing of immunobiological preparations is their stability, which consists in maintaining the main cultural, morphological, physiological, and productive properties in a series of generations. This paper describes a comprehensive methodological approach to testing strain stability using in vitro techniques.The purpose of this study was to conduct an integrated analysis of the stability in the strains that produce active components of the chemical cholera vaccine when preparing seed material and at the stage of cultivation.Materials and methods. Toxigenic strains of Vibrio сholerae 569B of the classical biovar, serovar Inaba and V. сholerae M-41 of the classical biovar, serovar Ogawa were used in the work. Cell morphology was monitored through light and transmission electron microscopy. Atomic force microscopy was applied to measure the main parameters of the bacterial cell. The strains were tested for the presence of ctxA gene in the chromosome using the “GenChol” test system with electrophoretic registration of results. Whole genome sequencing of the strains was performed on the Ion Torrent PGM platform using the Ion 318 Chip Kit and the Ion PGM Hi-Q View Chef 400 Kit. To determine the specific activity of cholera toxin and O-antigen, a DOT immunoassay with a conjugate based on staphylococcal protein A and colloidal gold nanoparticles was applied.Results and discussion. The stability of the main properties of industrial V. сholerae strains – producers of the active components of the chemical cholera vaccine has been confirmed using microbiological, immunochemical, molecular-genetic methods and microscopic analysis at all stages of cultivation, and the prospects for using the integrated methodological approach experimentally substantiated. Tailoring of these methods will make it possible to control the stability of producer strains, optimize cultivation conditions and, as a result, increase the yield of the necessary antigenic component of the vaccine

Воспроизводство трудового потенциала в период депопуляции 2019–2035 гг. и компенсирующая роль миграционного фактора

Purpose of the research. To examine the dynamics of reproduction of labor potential and labor supply in Russia for the period up to 2035, depending on the impact factors of its reproduction: generation change (changes in the proportion of cohort, entering and leaving at the age composition of the labor potential), fertility and mortality rates, migration balance in the individual age cohorts.  Materials and methods. The concept of “replacement of generations” is introduced. The coefficient of replacement of generations is developed and its value for labor potential of Russia for the period up to 2035 is calculated. The influence of factors of natural population movement on the dynamics of labor potential is analyzed. The compensating role of the migration factor in the conditions of labor potential reduction is calculated. Russian regions were grouped according to the following criteria: the direction and intensity of changes in the working-age population in 2020–2035 and the proportion of young people aged 0–15 years.  Results.  – There will be the reduction and aging of labor potential during the second stage of depopulation due to demographic factors.  – The decline in the working-age population in the second wave of depopulation is expected to be smaller than in the first wave.  – In Russia there will be a decrease in the replacement of generations in the contingent of people of the working age.  – The growth of Total Fertility Rate (TFR) in the forecast period should not be expected, because until 2030 a gradual decrease in the number of women of reproductive age is expected.  – The deepest failure in the population of the working age will be in 2020–2025 accounting for 1.7 million people according to the average variant of the forecast.  – In the forecast period, the labor force in the most productive age of 25–39 years will decrease by 10.5 million people, and the employment rate will decrease from 65.5% to 63.5%.  – Regional features of the formation of demand and supply of labor force in Russia cause the allocation of six homogeneous groups of regions.  – In order to compensate for the losses, it is necessary to increase the migration gain in the average version of ROSSTAT forecast by 2–2.5 times.  Conclusion. To meet the needs of the economy in the labor force in the forecast period, it is necessary to solve two interrelated tasks: compensation for the reduction of labor potential and ensuring the quality of labor potential necessary for the introduction of new technologies and digitalization of the economy. The unfavorable situation with the formation of labor resources is exacerbated by regional imbalances in the distribution of labor potential and differences in its quality across the country. In the future, migration is once again the only source of replenishment of labor potential and replacement of generations, despite the risks of quality losses due to the emigration of highly qualified persons and young people. It is necessary to take measures to increase the compensatory role of migration in the next five – six years. At the same time, migration policy measures should be considered in close conjunction with other measures to stimulate fertility and reduce mortality, ensuring a positive impact on the components of the population growth.  Цель работы: рассмотреть динамику воспроизводства трудового потенциала и предложение рабочей силы в России на период до 2035 г. в зависимости от воздействия факторов его воспроизвод­ства: замещения поколений (изменения соотношения численности когорт, входящих и выходящих по возрасту из состава трудового потенциала), рождаемости и смертности населения, миграци­онного сальдо в отдельных возрастных когортах.  Материалы и методы. Введено понятие «замещение поколе­ний». Разработан коэффициент замещения поколений и рассчи­тано его значение для трудового потенциала России на период до 2035 года. Проанализировано влияние факторов естественного движения населения на динамику трудового потенциала. Рас­считана компенсирующая роль фактора миграции в условиях сокращения трудового потенциала. Проведена группировка регионов России по признакам: направление и интенсивность изменения численности населения трудоспособного возраста в 2020–2035 гг. и доля молодежи в возрасте 0–15 лет.  Результаты  – Сокращение и постарение трудового потенциала в период второго этапа депопуляции обусловлено демографическими факторами.  – Прогнозируемое сокращение численности населения трудо­способного возраста во вторую волну депопуляции ожидается в меньших масштабах, чем в первую волну.  – В целом в России будет отмечаться снижение замещения поколений в контингенте лиц трудоспособного возраста.  – Ожидать роста СКР в прогнозном периоде не следует, поскольку до 2030 г. предвидится постепенное сокращение численности женщин репродуктивного возраста.  – На 2020–2025 гг. приходится наиболее глубокий провал в численности населения трудоспособного возраста: по среднему варианту прогноза он составит 1,7 млн чел.  – В прогнозном периоде численность рабочей силы в наиболее продуктивном возрасте 25–39 лет сократится на 10,5 млн чел., а уровень занятости сократится с 65,5% до 63,5%.  – Выявлены региональные особенности формирования спроса и предложения рабочей силы в России по 6 однородным группам регионов.  – Чтобы компенсировать потери необходимо увеличить в 2–2,5 раза миграционный прирост, заложенный в средний вариант прогноза Росстата.  Заключение. Для обеспечения потребностей экономики в рабочей силе в прогнозном периоде необходимо решать две взаимосвязанные задачи: компенсация сокращения трудового потенциала и обеспечение качества трудового потенциала, необходимого для внедрения новых технологий и цифровиза­ции экономики. Неблагополучная ситуация с формированием трудовых ресурсов усугубляется региональными диспропорци­ями в размещении трудового потенциала и различиями в его качестве по территории страны. В перспективе миграция становится вновь единственным источником пополнения тру­дового потенциала и замещения поколений, несмотря на риски качественных потерь за счет эмиграции лиц высокой квалифи­кации и молодежи. Необходимо принятие кардинальных мер по увеличению компенсирующей роли миграции уже в ближайшие пять-шесть лет. При этом, меры миграционной политики должны рассматриваться в тесной увязке с другими мерами по стимулированию рождаемости и снижению смертности, обеспечивая положительное воздействие на компоненты роста численности населения.

Assessment of Stability of Chemical Cholera Vaccine in a New Primary Packaging

The bivalent chemical cholera vaccine is the only drug for the prevention of cholera registered in the Russian Federation. The vaccine has been produced in glass bottles containing 210 tablets. At the same time, modern trends dictate the need to produce the drug in varying dispensing and more practical packaging for the convenience of the consumer.The aim of the work was to study the stability of the properties of the immunobiological medicinal product “Bivalent chemical cholera vaccine” with modified filling and in new primary packaging.Materials and methods. When studying the quality of bivalent chemical cholera vaccine batches, physicochemical parameters, formaldehyde content, specific activity and safety, abnormal toxicity, immunogenicity, and microbiological purity were assessed. Stability in terms of “specific activity” was evaluated using dot immunoassay.Results and discussion. As a result of this work, the use of several dispensing options and new primary packaging of cholera vaccine has been experimentally substantiated. The stability of the finished vaccine preparation has been established in the “accelerated aging” test and during long-term storage. The possibility of using dot immunoassay with a conjugate based on staphylococcal protein A, labeled with colloidal gold, to monitor the stability of cholera vaccine has been experimentally demonstrated

Магнитно-резонансная томография легких с парамагнитным контрастным усилением в динамическом контроле терапии рака легкого у больных с радиофобией: клинический случай

Till now the facilities of MRI with paramagnetic contrast enhancement (CE-MRI) in detection of lung tumors remain underused and almost ignored. A clinical case of primary detection and prospective follow-up of lung cancer in a patient whose MRI of the chest revealed a tumor lesion — a central cancer of the left lung, in particular a lesion of the bronchus of the lower lobe of the left lung. MRI of the chest with paramagnetic contrast enhancement was carried out as part of the whole body CE-MRI study after the complex therapy of breast cancer, and both the primary lung tumor and metastatic lesion of mediastinal — subbifurcation lymph nodes were revealed. With a transbronchial biopsy, the diagnosis of lung cancer was verified. Chemotherapy (ChT) was started using the vinorelbin/ carboplatin regimen. After this, the CE-MRI has been carried out during the whole period of followup of anti-cancer chemotherapy. At the CE-MRI during the first course of ChT visually the complete regression of the disease, also with clinical remission was achieved. However, the ChT scheme was not fully completed due to the patient’s departure for urgent private reasons. Two months later, the patient was examined again according to the same CE-MRI protocol, while a relapse of the disease was detected with a more pronounced lesion of the mediastinal lymph nodes than during the initial treatment. ChT with vinorelbine/carboplatin was again carried out under the control CE-MRI, this time completely. According to the chest CE-MRI, visual remission was achieved, with the disappearance of nodular tumor at the site of the previously identified primary tumor of lung cancer and metastatic lesions of lymph nodes. Thus, it was the CE-MRI which provided the early diagnosis and adequate control of treatment of the lung cancer with extensive local lymph nodes spread. After this CE-MRI, the whole body PET with 18F-fluorodeoxyglucose (FDG) was also performed and no signs of relapse or continued tumor growth were revealed. Five months after this stage, the patient did persist to stay completely preserved clinically, at work and socially active. Thus, the chest CE-MRI can be employed for the follow-up of the tumor process in lung cancer, as necessary, without radiation exposure, without limiting the number and frequency of studies. До сих пор возможности магнитно-резонансной томографии (МРТ) в диагностике и контроле лечения рака легкого практически мало востребованы из-за недостаточного опыта и знакомства с ними клиницистов-онкологов. Представлен клинический случай первичного выявления и проспективного наблюдения в ходе терапии рака легкого у пациентки, направленной неврологом поликлиники для проведения МР-томографии головного мозга в связи со стойкими головными болями, после перенесенного двумя месяцами ранее сомнительного эпизода заболевания COVID-19. При МРТ органов грудной клетки (ОГК) было выявлено опухолевое поражение — центральный рак слева с поражением бронха нижней доли левого легкого. МРТ ОГК с парамагнитны контрастным усилением (ПМКУ) выполнялась как часть исследования всего тела после проведенной комплексной терапии рака молочной железы, была выявлена как первичная опухоль рака легкого, так и метастатическое поражение средостенных — суббифуркационных лимфоузлов. Диагноз рака легкого был верифицирован при трансбронхиальной биопсии. В ходе дальнейших повторных контрольных исследований МРТ ОГК с ПМКУ выполнялась повторно и многократно. После начала химиотерапии (ХТ) c использованием схемы винорелбин/карбоплатин был достигнут по результатам МРТ с ПМКУ визуально полный регресс заболевания с клинической ремиссией. Однако полностью схема химиотерапии не была завершена в связи с отъездом пациентки по настоятельным частным причинам. Спустя два месяца пациентка была вновь обследована по тому же протоколу МРТ органов грудной клетки с парамагнитным контрастным усилением, при этом выявлен рецидив заболевания с более выраженным поражением лимфоузлов средостения, чем при первичном обращении. Вновь проведена под контролем МРТ ОГК с ПМКУ комплексная химиотерапия винорелбином/карбоплатином, на этот раз полностью. По данным контрольной МРТ ОГК с ПМКУ — достигнута визуальная ремиссия, с исчезновением узловых новообразований на месте ранее выявленной первичной опухоли рака легкого и метастатических поражений лимфоузлов. После МРТ с  ПМКУ также проведена ПЭТ всего тела с  18F-фтордезоксиглюкозой. Признаков рецидива или продолженного роста опухоли не выявлено. Спустя 5 мес после этого этапа пациентка была полностью сохранна клинически, активна профессионально и социально. Таким образом, МРТ ОГК с ПМКУ может быть использована для проведения проспективной повторной оценки состояния опухолевого процесса при раке легкого по необходимости, без лучевой нагрузки, без ограничения количества исследований

Discogenic non-radicular low back pain: a clinical case report

Back pain is often considered under the diagnostic heading “nonspecific pain” because of difficulties in identifying the primary source of pain in everyday clinical practice. However, despite the difficulties in identifying the specific etiology of chronic low back pain, diagnostic procedures can identify its source in 90% of patients. We report a clinical case of typical discogenic pain.The 6-week pain, which developed after barbell exercising in a 42-year-old man, resulted in the loss of professional employment. The pain was localized to the midline of the lower back (axial pain) and intensified in a sitting position. Computed tomography images demonstrated subchondral changes in L5-S1 vertebral bodies (Modic-1). A holistic diagnostic approach, including a vibration test, made it possible to diagnose the degenerative disc disease (L5-S1 intervertebral disk disease) with subacute discogenic pain. The patient received Dexalgin®25 at a dose of 25 mg x 3 times a day in combination with omeprazole 20 mg per day for 5 days, then the patient was switched to Nimesil 200 mg per day in two divided doses. A complex drug of the SYSADOA group containing glucosamine and chondroitin was used as adjuvant therapy. Pain intensity was reduced by 70 % at 6 weeks (2 points on VAS scale, which corresponds to the level of mild pain syndrome) as compared to the baseline level.This clinical case stresses the importance of accurate diagnosis of back pain and demonstrates the potential for successful combination non-surgical treatment of discogenic pain in primary outpatient settings

The labor potential reproduction in depopulation period of 2019–2035 and the compensating role of migration

Purpose of the research. To examine the dynamics of reproduction of labor potential and labor supply in Russia for the period up to 2035, depending on the impact factors of its reproduction: generation change (changes in the proportion of cohort, entering and leaving at the age composition of the labor potential), fertility and mortality rates, migration balance in the individual age cohorts.  Materials and methods. The concept of “replacement of generations” is introduced. The coefficient of replacement of generations is developed and its value for labor potential of Russia for the period up to 2035 is calculated. The influence of factors of natural population movement on the dynamics of labor potential is analyzed. The compensating role of the migration factor in the conditions of labor potential reduction is calculated. Russian regions were grouped according to the following criteria: the direction and intensity of changes in the working-age population in 2020–2035 and the proportion of young people aged 0–15 years.  Results.  – There will be the reduction and aging of labor potential during the second stage of depopulation due to demographic factors.  – The decline in the working-age population in the second wave of depopulation is expected to be smaller than in the first wave.  – In Russia there will be a decrease in the replacement of generations in the contingent of people of the working age.  – The growth of Total Fertility Rate (TFR) in the forecast period should not be expected, because until 2030 a gradual decrease in the number of women of reproductive age is expected.  – The deepest failure in the population of the working age will be in 2020–2025 accounting for 1.7 million people according to the average variant of the forecast.  – In the forecast period, the labor force in the most productive age of 25–39 years will decrease by 10.5 million people, and the employment rate will decrease from 65.5% to 63.5%.  – Regional features of the formation of demand and supply of labor force in Russia cause the allocation of six homogeneous groups of regions.  – In order to compensate for the losses, it is necessary to increase the migration gain in the average version of ROSSTAT forecast by 2–2.5 times.  Conclusion. To meet the needs of the economy in the labor force in the forecast period, it is necessary to solve two interrelated tasks: compensation for the reduction of labor potential and ensuring the quality of labor potential necessary for the introduction of new technologies and digitalization of the economy. The unfavorable situation with the formation of labor resources is exacerbated by regional imbalances in the distribution of labor potential and differences in its quality across the country. In the future, migration is once again the only source of replenishment of labor potential and replacement of generations, despite the risks of quality losses due to the emigration of highly qualified persons and young people. It is necessary to take measures to increase the compensatory role of migration in the next five – six years. At the same time, migration policy measures should be considered in close conjunction with other measures to stimulate fertility and reduce mortality, ensuring a positive impact on the components of the population growth

Use of inosine pranobex in frequently ill children

The follow-up group of «frequently ill children» is formed on the basis of criteria formulated by domestic pediatricians A.A. Baranov and V.Yu. Al’bitskiy, due to the high relevance of medical, social and economic problems caused by the increased morbidity in this category of patients especially with acute respiratory infections, with likely development of severe complications or the manifestation of chronic respiratory diseases. In general, the state of the immune system in frequently ill children is characterized by decreased local immunity and increased stress of systemic immunity, and the features of the functional immunity activity in this category of patients determine the various possibilities to affect immunity during the prevention and treatment of acute respiratory infections. This article discusses the features of the functional activity of the immune system in frequently ill children, as well as the possibilities of drug management of its disorders and the benefits of using inosine pranobex to prevent and treat respiratory infections in this category of patients. According to the international classification of drugs maintained by the World Health Organization, the drug belongs to the groups of immunomodulators (L) and antimicrobial antiviral drugs (J) for systemic use. It is proved that inosine pranobex effectively increases cellular and humoral immunity, and reduces non-specifically the viral replication capacity. During clinical trials, the drug proved to be a highly effective and safe component of the complex treatment of acute respiratory infections in frequently ill children. The use of inosine pranobex reduces the duration and intensity of symptoms of infectious respiratory tract diseases. The drug can be recommended for children with concomitant chronic respiratory tract diseases