Correction of the toxic effect of cyclophosphamide on hemopoiesis in animals with lewis lung carcinoma using low-molecular-weight sodium alginate

The influence of low-molecular-weight sodium alginate, which is administered as an isolated agent and in combination with cyclophosphamide, on the parameters of peripheral blood and bone marrow was studied in mice with Lewis lung carcinoma. It was shown that administration of sodium alginate with a molecular weight of 1–10 and 20–30 kDa to tumor-bearing animals prevents bone marrow failure by activating the process of regeneration of granulocytic hemopoietic stem cells that are damaged by a single injection or repetitive injections of a cytostatic agent, due to stimulation of the clonal activity of granulocytopoiesis precursors. As a result, this treatment prevents the progression of leukopenia

Internal gravity waves in the energy and flux budget turbulence-closure theory for shear-free stably stratified flows

We have advanced the energy and flux budget turbulence closure theory that takes into account a two-way coupling between internal gravity waves (IGWs) and the shear-free stably stratified turbulence. This theory is based on the budget equation for the total (kinetic plus potential) energy of IGWs, the budget equations for the kinetic and potential energies of fluid turbulence, and turbulent fluxes of potential temperature for waves and fluid flow. The waves emitted at a certain level propagate upward, and the losses of wave energy cause the production of turbulence energy. We demonstrate that due to the nonlinear effects more intensive waves produce more strong turbulence, and this, in turn, results in strong damping of IGWs. As a result, the penetration length of more intensive waves is shorter than that of less intensive IGWs. The anisotropy of the turbulence produced by less intensive IGWs is stronger than that caused by more intensive waves. The low-amplitude IGWs produce turbulence consisting up to 90% of turbulent potential energy. This resembles the properties of the observed high-altitude tropospheric strongly anisotropic (nearly two-dimensional) turbulence.Peer reviewe

Clinical and epidemiological characteristics and effectiveness of antiviral therapy for COVID-19 in children: The experience of the first year of the pandemic

Background. The use of antiviral agents can shorten the duration of the viral infection. The aim: to study the clinical and epidemiological features and the effectiveness of antiviral therapy for new coronavirus infection (COVID-19) in outpatient children.Materials and methods. From April 2020 to March 2021, 9334 outpatient children aged from 0 months to 17 years were randomly tested for new coronavirus infection. SARS-CoV-2 RNA was detected in oropharyngeal and nasal material by PCR. Patients with confirmed new coronavirus infection were prescribed interferon-alpha (IFN-α) intranasally, antiviral agents of systemic action. The control group consisted of children with COVID-19 who did not receive treatment.Results. When examining clinically healthy contact children, SARS-CoV-2 RNA was detected in 7.4 % of cases. In the structure of ARI, the specific weight of COVID-19 was 12.3 % with the peak incidence in April-May (up to 22.8 %) and NovemberDecember (up to 30.0 %). In half of the cases, children became infected in the family, and usually adults were the index patient. In 47.7 % of cases, an asymptomatic form of COVID-19 was registered without significant differences in patients of different ages. In one third of children with concomitant pathology, the disease was asymptomatic, in half it was mild, in other cases moderate severity was diagnosed. The clinical picture of COVID-19 did not differ from other ARIs. Anosmia (9.4 %) in half of the cases was combined with ageusia (4.4 %) and was significantly more common in boys. The duration of clinical manifestations in children of the control group and those who received antiviral therapy did not statistically significantly differ in mild and severity of the disease. Also, various antiviral therapy options did not significantly affect the duration of SARS-CoV-2 detection in children with various forms of COVID-19.Conclusion. In the first year of the pandemic, the novel coronavirus infection did not dominate the pattern of respiratory diseases in outpatient children. Further research is required to develop pediatric guidelines for the treatment of COVID-19 at the outpatient stage

Оценка активности демиелинизации у пациентов с рассеянным склерозом методом переноса намагниченности

Purpose: to study the activity of demyelination process in patients with multiple sclerosis using magnetization transfer effect.Materials and methods. Рatients group of 10 people aged from 19 to 48 years old with a confirmed diagnosis of multiple sclerosis was formed for clinical testing. Contrastcontaining and fat-containing substances scanned with offset frequency used as the material for the phantom studies. MRI investigation was performed on high field magnetic resonance tomograph with 1.5 Tesla magnetic field. To obtain T1-weighted images in the phantom experiment the Spin-Echo pulse sequence with parameters: TR = 650 ms, TE = 20 ms, FOV = 14 cm, MX = 96 × 256, STh = 4.7 mm with the imposition of a single pulse of magnetization transfer (MTS = 1) was used. Magnetization transfer ratio (MTR) was used to quantify the magnetization transfer effect. The Spin-Echo pulse sequence with the following parameters: TR = 621 ms, TE = 17 ms, FOV = 23.4 cm, MX = 208 × 320, STh = 5.0 mm was used in the clinical trial.After the administration of contrast medium the same pulse sequence with applying magnetization transfer pulse (MTC = 1) was used. Contrast ratio was calculated for evaluating the contrasting effect.Results. The greatest MTR value was obtained when the phantom study with a combination of frequency offset (Δf) and flip angle (FA(MT)): Δf = −210 Hz and FA(MT) = 600° respectively. Clinical approbation of this combination showed a statistically significant increase in contrast ratio (p < 0.05) between the demyelination foci and white brain matter in comparison with the sequence without magnetization transfer effect. In addition significant differences in MTR coefficients revealed between the intact white matter and demyelination foci (p < 0.05). The sensitivity of T1-weighted sequence with the magnetization transfer effect in identification of active foci of demyelination was significantly higher (p < 0.001) than that sensitivity of T1-weighted sequences without the magnetization transfer effect.Conclusion. The improved visualization of active foci of demyelination in patients with multiple sclerosis using a sequence with magnetization transfer effect with the following parameters: Δf = −210 Hz, FA(MT) = 600° due to the high values of contrast ratio compared with T1-Spin-Echo (p < 0.05) was shown and significant reduction in MTR coefficient in demyelination foci (p < 0.05).Цель исследования: оценка активности процесса демиелинизации у пациентов с рассеянным склерозом с использованием эффекта переноса намагниченности.Материал и методы. Для клинической апробации была сформирована группа пациентов из 10 человек  в возрасте от 19 до 48 лет с подтвержденным диагнозом рассеянного склероза. В качестве материала для фантомных исследований использовали контраст- и жиросодержащие вещества, сканированные со смещением резонансной частоты. МРТ-исследование проводили на высокопольном магнитно-резонансном томографе с индукцией магнитного поля 1,5 Тл. Для получения Т1-взвешенных изображений в фантомном эксперименте использовалась импульсная последовательность спин-эхо с параметрами: TR = 650 мс, TE = 20 мс, FOV = 14 см, MX = 96 × 256, STh = 4,7 мм с наложением одного импульса переноса намагниченности (МТС = 1). Для количественной оценки эффекта переноса намагниченности использовали коэффициент переноса намагниченности (MTR). При клиническом исследовании использовали импульсную последовательность спин-эхо с параметрами: TR = 621 мс, TE = 17 мс, FOV = 23,4 см, MX = 208 × 320, STh = 5,0 мм. Эту же импульсную последовательность, но с наложением импульса переноса намагниченности (MTC = 1), использовали после введения контрастного вещества. Для оценки контрастирующего эффекта рассчитывали коэффициент контраста.Результаты. Наибольшее значение MTR при фантомном исследовании получено при сочетании смещения частоты (Δf) и угла поворота (FA(MT)): Δf = −210 Гц и FA(MT) = 600° соответственно. Клиническая апробация данной комбинации показала статистически значимое повышение коэффициента контраста (p < 0,05) между очагами демиелинизации и белым веществом головного мозга в сравнении с последовательностью без эффекта переноса намагниченности. Кроме того, выявлено значимое различие коэффициентов MTR между интактным белым веществом и очагом демиелинизации (p < 0,05). Чувствительность Т1-взвешенной последовательности с эффектом переноса намагниченности значимо выше (р < 0,001) показателей чувствительности Т1-взвешенной последовательности без эффекта переноса намагниченности.Выводы. Показано улучшение визуализации активных очагов демиелинизации у пациентов с рассеянным склерозом при использовании Т1-взвешенной последовательности с эффектом переноса намагниченности с параметрами: Δf = −210 Гц, FA(MT) = 600° за счет высоких значений коэффициента контраста в сравнении с T1-взвешенной последовательностью на основе спинэхо (р < 0,05) и значимого снижения коэффициента MTR в очаге демиелинизации (p < 0,05)

Оценка своевременности вакцинации против коклюша детей первого года жизни и причин нарушения графика прививок

The maximum incidence of pertussis in young children confirms the importance of their timely immunization.The goal is – to study the timeliness of vaccination against whooping cough, causes of violation of the vaccination schedule in young children, the effect of recombinant interferon-a on the post-vaccination period.Materials and methods: the vaccination history and data on the course of the post-vaccination period after immunization with DPT and DaPT vaccines of 469 children at the age of 3–24 months were studied.Results. The analysis showed that 14,9% of the observed children were not vaccinated against whooping cough in a timely manner. Of these: 34,3% had a written refusal to vaccinate (5.1% of the total number of observed children), in 32,8% of cases, the vaccination schedule was violated due to late arrival of parents, 32,9% of children by the start of immunization had medical challenges, and only half of them had justified contraindications. Non-serious side effects associated with immunization were observed in 11.3% of cases, statistically more often with DTP (22,0%) compared with DaPT (5.,5%). General and local reactions, in general, were recorded on DPT (6,9% and 15,1%, respectively) and less often developed with the use of DaPT (1,0% and 4,5%, respectively). Within 1 month after immunization, 16,2% of the observed children had an acute respiratory viral infection of varying severity. Those who did not receive antiviral therapy more often carried the disease in a moderate and severe form, which in all cases led to the postponement of the administration of the second and third doses of the vaccine.Conclusion. To increase the timeliness of vaccination of children against whooping cough, medical professionals should persistently remind parents about the timing of turnout for the next vaccination, when making medical withdrawals, be guided by modern methodological documents and instructions for vaccines. The use of antiviral and immunomodulatory effects of IFN-alpha drugs allows us to comply with the recommended schedule for vaccination of children with a high risk of SARS in the post-vaccination period.Максимальная заболеваемость коклюшем детей раннего возраста подтверждает важность их своевременной иммунизации.Цель: изучить своевременность вакцинации против коклюша, причины нарушения графика прививок у детей раннего возраста, влияние препаратов рекомбинантного интерферона-aльфа на течение поствакцинального периода.Материалы и методы: изучен прививочный анамнез и данные о течении поствакцинального периода после иммунизации вакцинами АКДС и препаратами с бесклеточным коклюшным компонентом 469 детей в возрасте от 3 мес. до 24 мес.Результаты. Анализ показал, что 14,9% наблюдаемых детей оказались своевременно не привиты против коклюша, из них: у 34,3% оформлен письменный отказ от прививки (5,1% от общего числа наблюдаемых детей), в 32,8% случаев график вакцинации был нарушен из-за несвоевременной явки родителей, 32,9% детей к началу иммунизации имели медицинские отводы, причем только у половины противопоказания были обоснованные. Несерьезные побочные проявления, связанные с иммунизацией, наблюдались в 11,3% случаев, статистически чаще при введении АКДС (22,0%) по сравнению с бесклеточными коклюшными вакцинами (5,5%). Общие и местные реакции, в основном, регистрировались на АКДС (6,9% и 15,1% соответственно) и реже развивались при использовании препаратов с бесклеточным коклюшным компонентом (1,0% и 4,5% соответственно). В течение 1 месяца после иммунизации 73 ребенка (16,2%) перенесли острую респираторную вирусную инфекцию различной степени тяжести. Не получавшие противовирусную терапию чаще переносили заболевание в среднетяжелой и тяжелой форме, что во всех случаях привело к переносу срока введения второй и третьей дозы вакцины.Заключение. Для увеличения своевременности вакцинации детей против коклюша медицинские работники должны настойчиво напоминать родителям о сроках явки на очередную вакцинацию, при оформлении медицинских отводов, руководствоваться современными методическими документами и инструкциями к вакцинам. Использование противовирусного и иммуномодулирующего эффекта препаратов интерферон-альфа позволяет соблюсти рекомендованный график при вакцинации детей с высоким риском заболеваемости острой респираторной вирусной инфекцией в поствакцнальном периоде.

GRP78 Knockdown Enhances Apoptosis via the Down-Regulation of Oxidative Stress and Akt Pathway after Epirubicin Treatment in Colon Cancer DLD-1 Cells

INTRODUCTION: The 78-kDa glucose-regulated protein (GRP78) is induced in the cancer microenvironment and can be considered as a novel predictor of responsiveness to chemotherapy in many cancers. In this study, we found that intracellular reactive oxygen species (ROS) and nuclear factor erythroid 2-related factor 2 (Nrf2) nuclear translocation were higher in GRP78 knockdown DLD-1 colon cancer cells compared with scrambled control cells. METHODOLOGY/PRINCIPAL FINDINGS: Treatment with epirubicin in GRP78 knockdown DLD-1 cells enhanced apoptosis and was associated with decreased production of intracellular ROS. In addition, apoptosis was increased by the antioxidants propyl gallate (PG) and dithiothreitol (DTT) in epirubicin-treated scrambled control cells. Epirubicin-treated GRP78 knockdown cells resulted in more inactivated Akt pathway members, such as phosphorylated Akt and GSK-3β, as well as downstream targets of β-catenin expression. Knockdown of Nrf2 with small interfering RNA (siRNA) increased apoptosis in epirubicin-treated GRP78 knockdown cells, which suggested that Nrf2 may be a primary defense mechanism in GRP78 knockdown cells. We also demonstrated that epirubicin-treated GRP78 knockdown cells could decrease survival pathway signaling through the redox activation of protein phosphatase 2A (PP2A), which is a serine/threonine phosphatase that negatively regulates the Akt pathway. CONCLUSIONS: Our results indicate that epirubicin decreased the intracellular ROS in GRP78 knockdown cells, which decreased survival signaling through both the Akt pathway and the activation of PP2A. Together, these mechanisms contributed to the enhanced level of epirubicin-induced apoptosis that was observed in the GRP78 knockdown cells

Design and baseline characteristics of the finerenone in reducing cardiovascular mortality and morbidity in diabetic kidney disease trial

Background: Among people with diabetes, those with kidney disease have exceptionally high rates of cardiovascular (CV) morbidity and mortality and progression of their underlying kidney disease. Finerenone is a novel, nonsteroidal, selective mineralocorticoid receptor antagonist that has shown to reduce albuminuria in type 2 diabetes (T2D) patients with chronic kidney disease (CKD) while revealing only a low risk of hyperkalemia. However, the effect of finerenone on CV and renal outcomes has not yet been investigated in long-term trials. Patients and Methods: The Finerenone in Reducing CV Mortality and Morbidity in Diabetic Kidney Disease (FIGARO-DKD) trial aims to assess the efficacy and safety of finerenone compared to placebo at reducing clinically important CV and renal outcomes in T2D patients with CKD. FIGARO-DKD is a randomized, double-blind, placebo-controlled, parallel-group, event-driven trial running in 47 countries with an expected duration of approximately 6 years. FIGARO-DKD randomized 7,437 patients with an estimated glomerular filtration rate >= 25 mL/min/1.73 m(2) and albuminuria (urinary albumin-to-creatinine ratio >= 30 to <= 5,000 mg/g). The study has at least 90% power to detect a 20% reduction in the risk of the primary outcome (overall two-sided significance level alpha = 0.05), the composite of time to first occurrence of CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. Conclusions: FIGARO-DKD will determine whether an optimally treated cohort of T2D patients with CKD at high risk of CV and renal events will experience cardiorenal benefits with the addition of finerenone to their treatment regimen. Trial Registration: EudraCT number: 2015-000950-39; ClinicalTrials.gov identifier: NCT02545049

Quality of Education According to the Assessment of University’s Key Partners

The article addresses the problems of the quality of education in general, including from the perspective of employers. The authors believe that the mechanism for assessing the quality of education should be implemented through the active participation of the University’s key partners and employers in the educational process.The article presents the results of a study of the level of satisfaction with the quality of education of graduates estimated by enterprises that are the key partners of Orenburg State University (2020). The first set of questions involved an analysis of the degree of participation of employer organizations in the educational process and assessment of the level of training of university graduates. The second block included an assessment of personnel needs and demands on graduates when applying for a job, as well as an analysis of the prospects for developing forms of cooperation between employers in the region and the University.In conclusion, we offer a list of recommendations for improving the effectiveness of internal independent assessment of the quality of education with the involvement of representatives of employers. The list includes recommendations aimed at enhancing their participation in improving the system of training for the region’s economy