Compliance of the Directions and Programs of Training in Postgraduate Studies: The Transition Period

The new classification of scientific majors for which academic degrees are awarded and the amendments to the Federal Law “On Education in the Russian Federation”, which came into force on September 1, 2021, have significantly changed the list of scientific majors and the status of postgraduate studies. There is a need to establish the correspondence between scientific and pedagogical personnel training directions in postgraduate studies and scientific majors of the Classification 2021, in which academic degrees are awarded. The article presents an analysis of the adapting document “Fields of training in the postgraduate studies of OKSO 2016 – Scientific majors/branches of science of the Classification 2021” and considers measures on the way to reorganize the system of training and certification of academic degree holders

Chronic diseases of adults programmed in childhood

The conditions of human development during the stages of early ontogenesis are of great importance for human health throughout the rest of his life. The period of intrauterine development and childhood are vulnerable stages of organism formation, when metabolic processes have the greatest plasticity and can be subject to deformation. Exposure to a number of external factors during this period of time can have a significant impact on the functional activity of genes controlling neurotransmission, immune response, endocrine functions and, thus, program the spectrum of metabolic disorders that can lead later to the formation of chronic diseases: obesity, type 2 diabetes, atherosclerosis and diseases of cardiovascular system. Negative programming influence on the metabolic profile and cardiovascular risk is caused by such factors as maternal obesity, complicated pregnancy and childbirth, prematurity, early separation from the mother, violation of child feeding in the 1st year of life. The risk of early development of cardiovascular disease, metabolic syndrome, obesity and diabetes mellitus is significantly increased in individuals who have experienced traumatic stressors during childhood associated with economic disadvantage of the family, parental divorce, neglect, abuse, parental neglect, sexual violence, death of parents, family members, close friends, bullying in the children's community. An in-depth study of this problem, along with the development and organization of measures for monitoring and prevention, in the long term can reduce the burden of chronic non-infectious diseases, improve quality of life, reduce disability, incapacitation and mortality in the adult population.

МЕТАБОЛИЧЕСКИЕ ЭФФЕКТЫ СУБСТРАТНОГО АНТИГИПОКСАНТА НА ОСНОВЕ ЯНТАРНОЙ КИСЛОТЫ

The paper discusses promises for clinical use of substrate antihypoxants.Objective: to investigate the efficacy of succinate containing  substrate  antihypoxants  on  systemic  oxygen  consumption,  blood  buffer  capacity,  and  changes  in  the  mixed venous blood level of lactate when they are used in gravely sick patients and victims with marked metabolic posthypoxic disorders.Subjects and methods. The trial enrolled 30 patients and victims who had sustained an episode of severe hypoxia of mixed genesis, the severity of which was evaluated by the APACHE II scale and amounted to 23 to 30 scores with a 46 to 70.3% risk of death. The standard infusion program in this group involved the succinate-containing drug 1.5% reamberin solution  in  a  total  dose  of  800  ml.  A  comparison  group  included  15  patients  who  had  undergone  emergency  extensive surgery for abdominal diseases. 400 ml of 10% glucose solution was used as an infusion medium. Oxygen consumption (VO2ml/min) and carbon dioxide production (VCO2ml/min) were measured before infusion and monitored for 2 hours. Arterial blood gases and acid-base balance (ABB) parameters and mixed venous blood lactate levels were examined. Measurements were made before and 30 minutes after the infusion of reamberin or glucose solution.Results. Infusion of 1.5% reamberin solution was followed by a significant increase in minute oxygen consumption from 281.5±21.2 to 310.4±24.4 ml/min. CO2 production declined (on average, from 223.3±6.5 to 206.5±7.59 ml/min). During infusion of 10% glucose solution, all the patients of the comparison group showed a rise in oxygen consumption from 303.6±33.86 to 443.13±32.1 ml/min, i.e. about 1.5-fold. VCO2 changed similarly. The intravenous infusion of 800 ml of 1.5% reamberin solution raised arterial blood buffer capacity, which was reflected by changes in pH, BE, and HCO3. There was a clear trend for lactate values to drop in the mixed venous blood. The intravenous injection of 400 ml of 10% glucose solution caused no significant changes in major ABB indicators, which reinforced the statement that there is a difference in the metabolism of these substrates.Conclusion. The succinate-containing drugs are able to compensate for metabolic acidosis. Their use is followed by increased oxygen consumption  and  activated  aerobic  oxidation  processes.  The  basis  of  their  antihypoxant  properties  was  thought  to  be recovered intracellular aerobic metabolic processes due to corrected intracellular metabolic acidosis and increased blood  buffer capacity.В статье обсуждаются перспективы клинического применения субстратных антигипоксантов.Цель — изучить влияние сукцинат-содержащих субстратных антигипоксантов на системное потребление кислорода, буферную емкость крови, динамику содержания в смешанной венозной крови лактата при их применении у тяжелобольных и пострадавших с выраженными метаболическими постгипоксическими нарушениями.Материалы и методы. В исследование включили 30 больных и пострадавших, перенесших эпизод тяжелой гипоксии смешанного генеза, тяжесть состояния которых оценивали по шкале APACHE II, она составила от 23 до 30 баллов с риском летального исхода от 46 до 70,3%. В состав стандартной инфузионной программы этой группы был включен сукцинат-содержащий препарат — реамберин 1,5% в суммарной дозе 800 мл. Группа сравнения (n=15) была представлена больными, которым в экстренном порядке выполняли обширные операции по поводу заболеваний органов брюшной полости. В качестве инфузионной среды был использован 10% раствор глюкозы в количестве 400 мл. До начала инфузии, а затем в мониторном режиме на протяжении двух часов измеряли потребление O2(VO2мл/мин) и выделение CO2(VCO2мл/мин). Изучался газовый состав, параметры КОС артериальной крови, содержание лактата в смешанной венозной крови. Измерения проводили до начала инфузии раствора реамберина или глюкозы, а также через 30 минут после ее завершения.Результаты. Инфузия  1,5%  раствора  реамберина  сопровождалась  достоверным  увеличением минутного  потребления  кислорода  с 281,5±21,2 мл/мин до 310,4±24,4 мл/мин. Выделение CO2 при этом снизилось (в среднем с 223,3±6,5 до 206,5±7,59 мл/мин). У всех больных группы сравнения во время инфузии 10% раствора глюкозы наблюдали увеличение потребления кислорода с 303,6±33,86 до 443,13±32,1 мл/мин, то есть почти в 1,5 раза. Аналогичным образом изменилосьVCO2. Внутривенная инфузия 800 мл 1,5% раствора реамберина повышала буферную емкость артериальной крови, что проявлялось изменением PH, BE и HCO3. Отмечали явную тенденцию к снижению содержания лактата в смешанной венозной крови. При внутривенном введении 400 мл 10% раствора глюкозы достоверных изменений основных показателей КОС не отмечали, что подтверждает предположение о различии в метаболизме этих субстратов.Заключение.  Препараты,  содержащие  в  своем  составе  сукцинат,  способны  компенсировать  метаболический  ацидоз.  Их применение сопровождается увеличением потребления кислорода и активацией процессов аэробного окисления. Полагаем, что основу их антигипоксантных качеств составляет восстановление процессов внутриклеточного аэробного метаболизма благодаря коррекции внутриклеточного метаболического ацидоза и увеличения буферной емкости крови.

Antipyretic drugs: benefits and undesirable consequences

Fever is a defensive and adaptive reaction of the body that develops in response to the action of pathogenic stimuli. It often accompanies various infectious, autoimmune, oncohematological and other diseases. Due to the frequent significant deterioration of children's general health, the occurrence of fever in children gives rise to concern not only in parents, but also in pediatricians. According to temperature level, fever can be classified into different categories: subfebrile - 37.1 to 37.9 °C, moderate -38 to 39 °C, febrile - 39.1 to 41 °C and hyperthermic - above 41 °C. By clinical manifestation distinguish benign, or rose, and malignant, or white, fever. The need to use antipyretic drugs depends not only on the hight of the body temperature elevation, but also on the patient's general health. The clinical guidelines state that the use of acetylsalicylic acid, nimesulide and met-amizole to lower the body temperature in children is not recommended, due to high risk of adverse reactions. Ibuprofen and paracetamol are the drugs of choice to lower body temperature in children both in Russia and abroad. Over 120 comparative studies of these two drug formulations have shown their close efficacy, but ibuprofen is most preferred for the treatment of fever and pain. In order to lower body temperature, parents can uncontrollably use antipyretic drugs in various combinations and incorrect dosages, which leads to severe toxic effects. The article presents a clinical case of Reye's syndrome in a 10-year-old girl, which is most likely associated with the use of aspirin as an antipyretic

Catalytic sulfation of betulin with sulfamic acid : experiment and DFT calculation

Betulin is an important triterpenoid substance isolated from birch bark, which, together with its sulfates, exhibits important bioactive properties. We report on a newly developed method of betulin sulfation with sulfamic acid in pyridine in the presence of an Amberlyst(®)15 solid acid catalyst. It has been shown that this catalyst remains stable when being repeatedly (up to four cycles) used and ensures obtaining of sulfated betulin with a sulfur content of ~10%. The introduction of the sulfate group into the betulin molecule has been proven by Fourier-transform infrared, ultraviolet-visible, and nuclear magnetic resonance spectroscopy. The Fourier-transform infrared (FTIR) spectra contain absorption bands at 1249 and 835–841 cm(−1); in the UV spectra, the peak intensity decreases; and, in the nuclear magnetic resonance (NMR) spectra, of betulin disulfate, carbons С3 and С28 are completely shifted to the weak-field region (to 88.21 and 67.32 ppm, respectively) with respect to betulin. Using the potentiometric titration method, the product of acidity constants K(1) and K(2) of a solution of the betulin disulfate H(+) form has been found to be 3.86 × 10(–6) ± 0.004. It has been demonstrated by the thermal analysis that betulin and the betulin disulfate sodium salt are stable at temperatures of up to 240 and 220 °C, respectively. The density functional theory method has been used to obtain data on the most stable conformations, molecular electrostatic potential, frontier molecular orbitals, and mulliken atomic charges of betulin and betulin disulfate and to calculate the spectral characteristics of initial and sulfated betulin, which agree well with the experimental data

Четверта міжнародна наукова-практична конференція «Комп’ютерне моделювання в хімії і технологіях та системах сталого розвитку»

Запропоновано підхід до визначення константи швидкості розкладання диборану та товщини дифузійного шару в проточному термохімічному реакторі ізобарного типу за умов осадження твердого осаду у вигляді кристалічного бору на поверхні вуглецевих волокон.Approach for determination of constant speed of decomposition of diborane and thickness deffusive layer in the running thermo-chemical reactor of isobar type at the conditions of setting of incrustation as the crystalline boron on the surface of carbon fibres is offered.Предложен подход для определения константы скорости разложения диборана и толщины дифузионного слоя в проточном термохимическом реакторе изобарного типа в условиях осаждения твердого осадка в виде кристаллического бора на поверхности углеродных волокон

Анализ генома бактерий Bacillus amyloliquefaciens БИМ В-439Д

According to the results of the analysis of the complete nucleotide sequence of B. amyloliquefaciens subsp. plantarum BIM B-439D, it is established that the genome of the strain is unique and is represented by a single ring chromosome with a size of 3978134 base pair containing 46.5 % G/C-pairs. The key genetic loci determining synthesis of antimicro-bic metabolites are defined: lipopeptides (surfactin, fengycin, bacillomycin D), dipeptide (bacilysin), siderophor (bacillibac-tin), polyketide antibiotics (difficidin and oxydifficidin, bacillaene and macrolactin), bacteriocin (amylocyclicin) and peptide/ polyketide (putative - tyrocidin), restriction-modification systems and mobile genetic elements (IS-elements and prophages) are characterized. The identified features in the organization and localization of individual genetic determinants (for example, intact prophage of 37558 bp) can be used as reliable molecular genetic markers for fast identification of the strain when it is used commercially. The complete nucleotide sequence of the genome can serve as the basis for a detailed functional analysis of the practically significant properties of the microorganisms of the Bacillus group.Согласно результатам анализа полной нуклеотидной последовательности бактерий В. amyloliquefa-ciens subsp. plantarum БИМ В-439Д, установлено, что геном штамма является уникальным и представлен одной кольцевой хромосомой размером 3978134 пар нуклеотидов, содержащей 46,50 % Г/Ц-пар. Определены ключевые генетические локусы, детерминирующие синтез антимикробных метаболитов: липопептидов (сурфактин, фенгицин, бацилломицин D), дипептида (бацилизин), сидерофора (бациллибактин), поликетидных антибиотиков (диффици-дин/оксидиффицидин, бациллен и макролактин), циклического бактериоцина (амилоциклицин), а также пептида/ поликетида (предположительно - тироцидин), охарактеризованы системы рестрикции-модификации и мобильные генетические элементы (IS-элементы и профаги). Выявленные особенности в организации и локализации отдельных генетических детерминант (например, интактный профаг размером 37558 п. н.) могут использоваться в качестве надежных молекулярно-генетических маркеров для быстрой идентификации штамма при его коммерческом использовании. Полная нуклеотидная последовательность генома может служить основой для детального функционального анализа практически значимых свойств микроорганизмов группы Bacillus

Paracrine interactions between primary human macrophages and human fibroblasts enhance murine mammary gland humanization in vivo

Abstract Introduction Macrophages comprise an essential component of the mammary microenvironment necessary for normal gland development. However, there is no viable in vivo model to study their role in normal human breast function. We hypothesized that adding primary human macrophages to the murine mammary gland would enhance and provide a novel approach to examine immune-stromal cell interactions during the humanization process. Methods Primary human macrophages, in the presence or absence of ectopic estrogen stimulation, were used to humanize mouse mammary glands. Mechanisms of enhanced humanization were identified by cytokine/chemokine ELISAs, zymography, western analysis, invasion and proliferation assays; results were confirmed with immunohistological analysis. Results The combined treatment of macrophages and estrogen stimulation significantly enhanced the percentage of the total gland humanized and the engraftment/outgrowth success rate. Timecourse analysis revealed the disappearance of the human macrophages by two weeks post-injection, suggesting that the improved overall growth and invasiveness of the fibroblasts provided a larger stromal bed for epithelial cell proliferation and structure formation. Confirming their promotion of fibroblasts humanization, estrogen-stimulated macrophages significantly enhanced fibroblast proliferation and invasion in vitro, as well as significantly increased proliferating cell nuclear antigen (PCNA) positive cells in humanized glands. Cytokine/chemokine ELISAs, zymography and western analyses identified TNFα and MMP9 as potential mechanisms by which estrogen-stimulated macrophages enhanced humanization. Specific inhibitors to TNFα and MMP9 validated the effects of these molecules on fibroblast behavior in vitro, as well as by immunohistochemical analysis of humanized glands for human-specific MMP9 expression. Lastly, glands humanized with macrophages had enhanced engraftment and tumor growth compared to glands humanized with fibroblasts alone. Conclusions Herein, we demonstrate intricate immune and stromal cell paracrine interactions in a humanized in vivo model system. We confirmed our in vivo results with in vitro analyses, highlighting the value of this model to interchangeably substantiate in vitro and in vivo results. It is critical to understand the signaling networks that drive paracrine cell interactions, for tumor cells exploit these signaling mechanisms to support their growth and invasive properties. This report presents a dynamic in vivo model to study primary human immune/fibroblast/epithelial interactions and to advance our knowledge of the stromal-derived signals that promote tumorigenesis

PEDIATRICIAN’S APPROACH TO THE CHOICE OF MEDICATION AGAINST COUGH IN CHILDREN

Cough is a common symptom in respiratory pathology which is associated with 30% of all visits to therapist and more than 50% to pediatrician, especially during the period of respiratory infection outbreak. Cough (Latin tussis) is a natural reflex to clear airways. The spectrum of diseases accompanied by cough is varied, thus it is required from a doctor to understand the etiological causes and pathogenic mechanisms of its development to make the adequate choice of therapy