ПРОГНОЗУВАННЯ БАКТЕРІЙНИХ ІНФЕКЦІЙНИХ УСКЛАДНЕНЬ У ПАЦІЄНТІВ ПРИ ТРАНСПЛАНТАЦІЇ ГЕМОПОЕТИЧНИХ СТОВБУРОВИХ КЛІТИН

Results of original study of risk factors of bacterial infectious complications during haematopoietic stem cell transplantation are presented in this article. Authors have conducted a complex analysis of effectiveness of sepsis biomarkers (procalcitonin, presepsin, C-reactive protein) among haematopoietic stem cell transplant recipients.Представлено результати оригінального дослідження, присвяченого визначенню чинників ризику розвитку бактерійних інфекційних ускладнень при трансплантації гемопоетичних стовбурових клітин. Авторами виконаний комплексний аналіз ефективності застосування біологічних маркерів інфекцій кровоплину (прокальцитоніну, пресепсину, С-реактівного білка) у реципієнтів гемопоетичних стовбурових клітин

СИСТЕМА МОБИЛЬНОГО МОНИТОРИНГА ГИДРОПРИВОДА НАВЕСНЫХ УСТРОЙСТВ ЭНЕРГОНАСЫЩЕННЫХ ТРАКТОРОВ

The paper presents results pertaining to creation of national mobile monitoring system for  suspension hydraulic drives  in respect to high-power “Belarus” tractors. A monitoring system schematic diagram has been developed and channels for data accumulation and processing have been determined in the paper. The paper reveals dependences for determination of residual resources of the hydraulic drive. A tractor “Belarus 3022” has been used for test of the proposed system and it has  proved its operating capability.Приводятся результаты по созданию отечественной системы мобильного мониторинга гидропривода навесных устройств применительно к энергонасыщенным тракторам «Беларус». Разработана схема системы мониторинга и установлены каналы сбора и обработки инфор- мации. Приведены зависимости по определению остаточного ресурса гидропривода. Предлагаемая система была апробирована на тракторе «Беларус-3022» и показала свою работоспособность

Local Induction of Immunosuppressive CD8+ T Cells in the Gut-Associated Lymphoid Tissues

Background: In contrast to intestinal CD4 + regulatory T cells (Tregs), the generation and function of immunomodulatory intestinal CD8 + T cells is less well defined. To dissect the immunologic mechanisms of CD8 + T cell function in the mucosa, reactivity against hemagglutinin (HA) expressed in intestinal epithelial cells of mice bearing a MHC class-I-restricted T-cellreceptor specific for HA was studied. Methodology and Principal Findings: HA-specific CD8 + T cells were isolated from gut-associated tissues and phenotypically and functionally characterized for the expression of Foxp3 + and their suppressive capacity. We demonstrate that intestinal HA expression led to peripheral induction of HA-specific CD8 + Foxp3 + T cells. Antigen-experienced CD8 + T cells in this transgenic mouse model suppressed the proliferation of CD8 + and CD4 + T cells in vitro. Gene expression analysis of suppressive HA-specific CD8 + T cells revealed a specific up-regulation of CD103, Nrp1, Tnfrsf9 and Pdcd1, molecules also expressed on CD4 + T reg subsets. Finally, gut-associated dendritic cells were able to induce HA-specific CD8 + Foxp3 + T cells. Conclusion and Significance: We demonstrate that gut specific antigen presentation is sufficient to induce CD8 + T regs in vivo which may maintain intestinal homeostasis by down-modulating effector functions of T cells

Urological tactics in cases of gestational pyelonephritis

Gestational pyelonephritis is a state of the art in practice of urological, gynecological, microbiogical, dermatovenerological and immunological departments. Firstly it’s related with gestational pyelonephritis in a past medical history: complications in pre- and postnatal periods, miscarriage of pregnancy and stillbirth, progression of chronical desease that leading to woman disability. In addition, gestational pyelonephritis has a negative affection on a fetus status and child health. These problems are loom large in social and medical domain.Острый гестационный пиелонефрит вновь и вновь обращает на себя внимание врачей многих специальностей: урологов, акушеров-гинекологов, микробиологов, дерматовенерологов, иммунологов. В первую очередь, это обусловлено проблемами, которые имеют причинно-следственную связь с перенесенным гестационным пиелонефритом: осложнения в дородовом и послеродовом периодах, невынашивание беременности и мертворождение, развитие хронических заболеваний у женщин, порой приводящих к инвалидизации. Несомненно, гестационный пиелонефрит влияет на состояние плода и соответственно на здоровье ребенка. Эти проблемы относятся к категории чрезвычайно важных социальных и медицинских вопросов

Constitutively active Lyn kinase causes a cutaneous small vessel vasculitis and liver fibrosis syndrome

Neutrophilic inflammation is a hallmark of many monogenic autoinflammatory diseases; pathomechanisms that regulate extravasation of damaging immune cells into surrounding tissues are poorly understood. Here we identified three unrelated boys with perinatal-onset of neutrophilic cutaneous small vessel vasculitis and systemic inflammation. Two patients developed liver fibrosis in their first year of life. Next-generation sequencing identified two de novo truncating variants in the Src-family tyrosine kinase, LYN, p.Y508*, p.Q507* and a de novo missense variant, p.Y508F, that result in constitutive activation of Lyn kinase. Functional studies revealed increased expression of ICAM-1 on induced patient-derived endothelial cells (iECs) and of β2-integrins on patient neutrophils that increase neutrophil adhesion and vascular transendothelial migration (TEM). Treatment with TNF inhibition improved systemic inflammation; and liver fibrosis resolved on treatment with the Src kinase inhibitor dasatinib. Our findings reveal a critical role for Lyn kinase in modulating inflammatory signals, regulating microvascular permeability and neutrophil recruitment, and in promoting hepatic fibrosis

A microRNA profile of human CD8(+) regulatory T cells and characterization of the effects of microRNAs on Treg cell-associated genes.

Recently, regulatory T (Treg) cells have gained interest in the fields of immunopathology, transplantation and oncoimmunology. Here, we investigated the microRNA expression profile of human natural CD8(+)CD25(+) Treg cells and the impact of microRNAs on molecules associated with immune regulation. We purified human natural CD8(+) Treg cells and assessed the expression of FOXP3 and CTLA-4 by flow cytometry. We have also tested the ex vivo suppressive capacity of these cells in mixed leukocyte reactions. Using TaqMan low-density arrays and microRNA qPCR for validation, we could identify a microRNA 'signature' for CD8(+)CD25(+)FOXP3(+)CTLA-4(+) natural Treg cells. We used the 'TargetScan' and 'miRBase' bioinformatics programs to identify potential target sites for these microRNAs in the 3'-UTR of important Treg cell-associated genes. The human CD8(+)CD25(+) natural Treg cell microRNA signature includes 10 differentially expressed microRNAs. We demonstrated an impact of this signature on Treg cell biology by showing specific regulation of FOXP3, CTLA-4 and GARP gene expression by microRNA using site-directed mutagenesis and a dual-luciferase reporter assay. Furthermore, we used microRNA transduction experiments to demonstrate that these microRNAs impacted their target genes in human primary Treg cells ex vivo. We are examining the biological relevance of this 'signature' by studying its impact on other important Treg cell-associated genes. These efforts could result in a better understanding of the regulation of Treg cell function and might reveal new targets for immunotherapy in immune disorders and cancer

Exome Chip Meta-analysis Fine Maps Causal Variants and Elucidates the Genetic Architecture of Rare Coding Variants in Smoking and Alcohol Use

BACKGROUND: Smoking and alcohol use have been associated with common genetic variants in multiple loci. Rare variants within these loci hold promise in the identification of biological mechanisms in substance use. Exome arrays and genotype imputation can now efficiently genotype rare nonsynonymous and loss of function variants. Such variants are expected to have deleterious functional consequences and to contribute to disease risk. METHODS: We analyzed similar to 250,000 rare variants from 16 independent studies genotyped with exome arrays and augmented this dataset with imputed data from the UK Biobank. Associations were tested for five phenotypes: cigarettes per day, pack-years, smoking initiation, age of smoking initiation, and alcoholic drinks per week. We conducted stratified heritability analyses, single-variant tests, and gene-based burden tests of nonsynonymous/loss-of-function coding variants. We performed a novel fine-mapping analysis to winnow the number of putative causal variants within associated loci. RESULTS: Meta-analytic sample sizes ranged from 152,348 to 433,216, depending on the phenotype. Rare coding variation explained 1.1% to 2.2% of phenotypic variance, reflecting 11% to 18% of the total single nucleotide polymorphism heritability of these phenotypes. We identified 171 genome-wide associated loci across all phenotypes. Fine mapping identified putative causal variants with double base-pair resolution at 24 of these loci, and between three and 10 variants for 65 loci. Twenty loci contained rare coding variants in the 95% credible intervals. CONCLUSIONS: Rare coding variation significantly contributes to the heritability of smoking and alcohol use. Fine-mapping genome-wide association study loci identifies specific variants contributing to the biological etiology of substance use behavior.Peer reviewe

MOBILE MONITORING SYSTEM FOR SUSPENSION HYDRAULIC DRIVES OF HIGH-POWER TRACTORS

The paper presents results pertaining to creation of national mobile monitoring system for  suspension hydraulic drives  in respect to high-power “Belarus” tractors. A monitoring system schematic diagram has been developed and channels for data accumulation and processing have been determined in the paper. The paper reveals dependences for determination of residual resources of the hydraulic drive. A tractor “Belarus 3022” has been used for test of the proposed system and it has  proved its operating capability

ANALYSIS OF THE FUNCTIONAL STATE OF MAIN TRANSPORT SYSTEMS OF BLOOD PLASMA OF PATIENTS WITH ACUTE LEUKEMIA AND CHRONIC MYELOGENOUS LEUKEMIA AFTER TRANSPLANTATION THE HEMATOPOIETIC STEM CELLS BY FLUORESCENT PROBES METHOD

Using the fluorescent probes method the conformational changes in albumin have been found in case of chemotherapy high dozes applied for treatment of patients with acute myeloid leukemia, as well as the inflammatory process has been decreased after the transplantation of hematopoietic stem cells