Predicting the severity of viral bronchiolitis in children

Acute viral bronchiolitis is one of the common causes of hospitalization and mortality, especially among children in the first year of life who have risk factors (prematurity, congenital heart defects, bronchopulmonary dysplasia, immunosuppression). As factors associated with the severe course of bronchiolitis, along with the traditional ones, single nucleotide polymorphisms of the genes of the immune response molecules can be considered.The aim. Based on the analysis of clinical, laboratory and molecular genetic parameters, to identify prognostic criteria for the severe course of acute viral bronchiolitis in children.Materials and methods. The study included 106 children with acute viral bronchiolitis (severe course – 34, mild course – 72), the etiology of which in 67.9 % was respiratory syncytial virus. Forty-seven anamnestic, clinical, traditional laboratory and molecular genetic parameters were assessed as prognostic criteria. Determination of SNP genes of cytokines IL-4 (C-589T), IL-10 (G-1082A), IL-10 (C-592A), IL-10 (C-819T), TNF-α (G-308A), IL-17A (G197A), IL-17F (His161Arg), TLR2-753ArgGln, TLR6-Ser249Pro in venous blood was carried out by the polymerase chain reaction method.Results. An additional criterion for the risk of developing a severe course of bronchiolitis can be the mutant genotype (AA) SNP of the IL-10 gene (C-592A), which was detected exclusively in the group of patients with severe bronchiolitis, increasing the risk of developing a severe disease by 16.11 times (OR = 16.11; 95 % CI: 0.81–121.22, p = 0.02) in conjunction with already established modifying factors: the presence of congenital heart disease, bronchopulmonary dysplasia, prematurity, birth weight < 1500 g. Based on a comprehensive assessment of the established risk factors, a method has been developed that allows calculate the likelihood of developing a severe course of acute viral bronchiolitis. Conclusion. The use of the developed prediction method will not only increase the likelihood of developing severe acute viral bronchiolitis in children, but also determine the priority group among children with predictors of severe viral bronchiolitis for priority immunoprophylaxis against RS-virus infection

Composition, Stability, and Paramagnetic Birefringence of Erbium(III) and Thulium(III) D- and DL-Tartrates

pH and paramagnetic birefringence measurements in tandem with mathematical modeling were applied to study the formation of erbium(III) and thulium(III) D- and DL-tartrates. The paramagnetic birefringence constants were calculated for these tartrates

Paramagnetic birefringence of heteronuclear erbium(III), thulium(III), and iron(III) d- and dl-tartrates

Formation of heteronuclear erbium(III), thulium(III), and iron(III) d- and dl-tartrates was studied by proton magnetic relaxation, pH-metry, and paramagnetic birefringence in combination with mathematical simulation. The paramagnetic birefringence constants mP of the complexes were calculated

Роль полиморфизма генов некоторых молекул иммунного ответа в развитии острого вирус-индуцированного бронхиолита

The aim of research: To investigate the genetic polymorphism of immune response molecules (TNFα-308G> A (rs1800629), IL4-589C>T (rs2243250), IL10-592C> A (rs1800872), IL10-819C> T (rs1800871), IL10-1082G>A (rs1800896), IL-17A-197G> A (rs2275913), IL- 17F-161His> Arg (rs763780), TLR-2-753Arg>Gln (rs5743708), TLR-6-249Ser>Pro (rs5743810) and assess their prognostic value in the development of acute virus-induced bronchiolitis.Materials and methods. The study included children of the first year of life, whose average age was 4.2 ± 3.7 months. The main group consisted of 106 patients with moderate and severe acute viral bronchiolitis, more often associated with respiratory syncytial virus (56.6%). The control group consisted of 100 healthy children of the same age who had no signs of acute respiratory infection at the time of examination and did not receive passive immunoprophylaxis of respiratory syncytial infection. Genotyping was performed using the polymerase chain reaction method. The analysis of the results included the compliance with the Hardy-Weinberg law, the χ 2 test, the relative chance, and its 95% confidence interval. To assess the distribution of the claimed gene polymorphisms and their alleles, we used the general (χ2 test, df =2) and multiplicative (χ2 test, df =1) inheritance models.Results. It was revealed that the risk of developing acute viral bronchiolitis is increased compared to the healthy population in carriers of the following genotypes: CC, ST gene IL10-819C> T (rs1800871), GG, AA gene IL-17A-197G> A (rs2275913), HisHis gene IL-17F-161His> Arg (rs763780), SerSer, SerPro gene TLR-6-249Ser> Pro (rs5743810), GG gene TNF-α-308G>A (rs1800629). The TT genotype of the IL10-819C>T (rs1800871) gene is associated with a high risk of developing bacterial complications (pneumonia) in viral bronchiolitis. Carriers of genotypes AA, CC of the IL10-592C> A (rs1800872) gene have an increased likelihood of a severe course of viral bronchiolitis.Conclusion. Genetic analysis of gene polymorphism IL10-592C> A (rs1800872), IL10-819C> T (rs1800871), IL-17A-197G> A (rs2275913), IL-17F-161His> Arg (rs763780), TLR-6-249Ser> Pro (rs5743810), TNF-α-308 G>A (rs1800629) can be used as a personalized developmental criterion acute virus-induced bronchiolitis in children, determining the severity of its course and the likelihood of complications.Цель: исследовать генетический полиморфизм молекул иммунного ответа (TNFα-308G>A (rs1800629), IL4-589C>T (rs2243250), IL10-592C>A (rs1800872), IL10-819C>T (rs1800871), IL10-1082G>A (rs1800896), IL-17A-197G>A (rs2275913), IL-17F-161His>Arg (rs763780), TLR2-753 Arg>Gln (rs5743708), TLR-6-249 Ser>Pro (rs5743810) и оценить их прогностическое значение в развитии острого вирус-индуцированного бронхиолита.Материалы и методы. В исследование включены дети первого года жизни, средний возраст которых составил 4,2±3,7 месяца. Основная группа – 106 пациентов с острым вирусным бронхиолитом средней и тяжелой степени тяжести, чаще ассоциированным с респираторно-синцитиальным вирусом (56,6%). Группа контроля – 100 здоровых детей аналогичного возраста, не имевших признаков острой респираторной инфекции на момент обследования и не получавших пассивную иммунопрофилактику респираторно-синцитиальной инфекции. Генотипирование проведено методом полимеразной цепной реакции. Анализ результатов включал соответствие закону Харди – Вайнберга, χ2-тест, относительный шанс и его 95% доверительный интервал. Для оценки распределения заявленных полиморфизмов генов и их аллелей использовали общую (χ2-тест, df=2) и мультипликативную (χ2-тест, df=1) модели наследования.Результаты. Выявлено, что риск развития острого вирусного бронхиолита повышен по сравнению со здоровой популяцией у носителей следующих генотипов: СС, СТ гена IL10-819C>T (rs1800871), GG, АА гена IL-17A-197G>A (rs2275913), HisHis гена IL-17F-161His>Arg (rs763780), SerSer, SerPro гена TLR-6-249Ser>Pro (rs5743810), GG гена TNF-α-308G>A (rs1800629). Генотип ТТ гена IL10-819C>T (rs1800871) ассоциирован с высоким риском развития бактериальных осложнений (пневмонии) при вирусном бронхиолите. Носители генотипов АА, СС гена IL10-592C>A (rs1800872) имеют повышенную вероятность тяжелого течения вирусного бронхиолита.Заключение. Генетический анализ полиморфизма генов IL10-592C>A (rs1800872), IL10-819C>T (rs1800871), IL-17A-197G>A (rs2275913), IL-17F-161His>Arg (rs763780), TLR-6-249Ser>Pro (rs5743810), TNF-α-308G>A (rs1800629) может использоваться в качестве персонифицированного критерия развития острого вирус-индуцированного бронхиолита у детей, определения тяжести его течения и вероятности формирования осложнений

Phage therapy in antibiotic resistant pneumonia: immunomodulation or redistribution?

Our report concerns the observations made during the treatment of pneumonia with individually selected bacteriophages in HCAI patients on mechanical ventilation. 19 patients on mechanical ventilation whose condition was complicated by antibiotic-resistant pneumonia were examined. The treatment of patients was supplemented with phage therapy, bacteriophages were selected individually for each patient, taking into account the microbial etiology of the disease (Pseudomonas aeruginosa, Кlebsiella pneumoniae, Acinetobacter baumanii). Immunophenotyping of blood lymphocytes was carried out using 2-3-parameter flow cytometry. The functional activity of blood leukocytes was assessed by their ability to produce IFNα and IFNγ during cultivation. The level of interferons production in supernatants collected after cultivation was quantitatively evaluated both by their concentration (ELISA, reagents from “Vector-Best-Europe”, Russia) and by their biological activity. Statistical processing of the results was carried out using the Statistica 6 program according to the nonparametric Mann-Whitney U-test. In the course of successful phage therapy with individually selected bacteriophages overcoming of lymphopenia (if there was one) and an increase in both the number and functional activity of peripheral blood lymphocytes in all patients with pneumonia observed are noted. The relationship between the microbial load (mono- or mixed infection, the number of CFU pathogens of pneumonia, the need for repeated courses of phage therapy) and the degree of deficiency in one or another subpopulation of lymphocytes was not detected. Activation of the immune system achieved after one course of phage therapy was maintained for at least 3 weeks after phage administration was discontinued

REDD1 Protects Osteoblast Cells from Gamma Radiation-Induced Premature Senescence

Radiotherapy is commonly used for cancer treatment. However, it often results in side effects due to radiation damage in normal tissue, such as bone marrow (BM) failure. Adult hematopoietic stem and progenitor cells (HSPC) reside in BM next to the endosteal bone surface, which is lined primarily by hematopoietic niche osteoblastic cells. Osteoblasts are relatively more radiation-resistant than HSPCs, but the mechanisms are not well understood. In the present study, we demonstrated that the stress response gene REDD1 (regulated in development and DNA damage responses 1) was highly expressed in human osteoblast cell line (hFOB) cells after γ irradiation. Knockdown of REDD1 with siRNA resulted in a decrease in hFOB cell numbers, whereas transfection of PCMV6-AC-GFP-REDD1 plasmid DNA into hFOB cells inhibited mammalian target of rapamycin (mTOR) and p21 expression and protected these cells from radiation-induced premature senescence (PS). The PS in irradiated hFOB cells were characterized by significant inhibition of clonogenicity, activation of senescence biomarker SA-β-gal, and the senescence-associated cytokine secretory phenotype (SASP) after 4 or 8 Gy irradiation. Immunoprecipitation assays demonstrated that the stress response proteins p53 and nuclear factor κ B (NFkB) interacted with REDD1 in hFOB cells. Knockdown of NFkB or p53 gene dramatically suppressed REDD1 protein expression in these cells, indicating that REDD1 was regulated by both factors. Our data demonstrated that REDD1 is a protective factor in radiation-induced osteoblast cell premature senescence

Disorder Predictors Also Predict Backbone Dynamics for a Family of Disordered Proteins

Several algorithms have been developed that use amino acid sequences to predict whether or not a protein or a region of a protein is disordered. These algorithms make accurate predictions for disordered regions that are 30 amino acids or longer, but it is unclear whether the predictions can be directly related to the backbone dynamics of individual amino acid residues. The nuclear Overhauser effect between the amide nitrogen and hydrogen (NHNOE) provides an unambiguous measure of backbone dynamics at single residue resolution and is an excellent tool for characterizing the dynamic behavior of disordered proteins. In this report, we show that the NHNOE values for several members of a family of disordered proteins are highly correlated with the output from three popular algorithms used to predict disordered regions from amino acid sequence. This is the first test between an experimental measure of residue specific backbone dynamics and disorder predictions. The results suggest that some disorder predictors can accurately estimate the backbone dynamics of individual amino acids in a long disordered region

Случай тяжелого трихинеллеза у девочки-подростка в Самарской области

Discribe the case of severe flow of а trichinosis in a girl 15 years old. The symptoms are an acute to x ico-allergological syndrome, generalized swelling myalgia and myasthenia with the full adynamia, infectios-toxicology kidney, an acute hypoalbuminemia with development polyserositis, adsence eosinophilia.Описан случай тяжелого течения трихинеллеза у девочки 15 лет, маркерами которого являлись: выраженный токсико-аллергический синдром, генерализованные отеки, миалгии и миастении с полной адинамией, инфекционно-токсическая почка, выраженная гипоальбуминемия с развитием полисерозита, отсутствие эозинофилии