Long-term β-cells autoimmune destruction markers persistence and residual C-peptide secretion in type 1 diabetes mellitus

Backgraund: It believed that autoimmune process maintained only during the first 5 years of diabetes mellitus type 1 (T1D). Recently scientists discovered the high levels of islet autoantibodies (Ab) in long-standing T1D and some of these patients had residual insulin secretion, determined by the level of C-peptide. According to various sources, the prevalence of such observations ranges from 12 to 48%.Aims: The aim of our study was to assess the duration of autoimmune β-cells destruction markers persistence and residual fasting C-peptide secretion in the long-standing T1D, as well as to determine the possible causes and patterns of these processes.Materials and methods: In the study included 237 patients (91 men, 146 women) with T1D. Patients divided in 4 groups, according to disease duration: а — up to 1 year, n=69 (29%); b — 1–5 years, 52 (22%); c — 5–10 years, 57 (24%); d — more than 10 years, 59 (25%). Ab to glutamic acid decarboxylase (GADA), tyrosine phosphatase-like IA-2 (IA2) and zinc T8 (ZnT8A) were detected by Enzyme Immunoassay. Also detected C-peptide levels and retrospectively HbA1с.Results: Antibodies to antigens of β-cell components were detected in 26 (37%) patients in group A, in 17 patients (33%) in group B, in 15 (29%) in group C and in 14 (23%) — G.In the control group (n = 19), an increased level of antibodies was not revealed. Fasting C-peptide levels were as follows: in group «A» — 0.86 ng / ml [0.53; 1.4], «B» — 0.65 ng / ml [0.27; 0.98], « B «- 0.19 ng / ml [0.17; 0.33],» D «- 0.01 ng / ml [0.01; 0.01]. However, in 13 (22%) patients in group D, fasting C-peptide levels were more than 0.09 ng / ml.Conclusion: The data obtained indicate a long-term persistence of markers of the autoimmune process in patients with T1DM. In groups with a long (more than 5 years) course of T1DM, levels of fasting C-peptide more than 30 pmol/L (0.09 ng / ml or 0.03 nmol / L) were noted in 39 (33.6%) cases

Infectious bursal disease virus: identification of the novel genetic group and reassortant viruses

The results of the phylogenic analysis of the nucleotide sequence of the IBDV A and B genome segments have been presented. Traditionally the IBDV isolates are classified based on the phylogenic analysis of the hypervariable region of the VP2 gene. The analysis of the VP2 gene segments of the isolates detected in the Russian Federation demonstrated that most of them belong to the genetic group comprising highly virulent IBDV isolates. However, not all isolates belonging to one genetic group have the same phenotypic characteristics. This is related to the fact that the virulence is determined not only based on the characteristics of the VP2 gene (A segment) but on the characteristics of the VP1 gene (B segment) as well. The IBDV genome segmentation allows formation of reassortant viruses which can be identified as a result of the genome segment analysis. The phylogenic analysis of the nucleotide sequences of VP2 and VP1 genes of 28 IBDV isolates detected at RF, Ukrainian and Kazakh poultry establishments in 2007 and 2019 showed that 15 of them are reassortant viruses. Different combinations of the genome segments have been identified among these reassortant viruses. Detection of different combinations of IBDV genome segments is indicative of the fact that the heterogeneous virus population circulates on the poultry farms. Pathogenicity studies of the three IBDV isolates showed that the most virulent was an isolate having two genome segments characteristic of the highly virulent virus. Two reassortant viruses having only one genome segment A or B, characteristic of the infectious bursal disease, demonstrated less pronounced virulent properties

Aurora kinase A drives the evolution of resistance to third-generation EGFR inhibitors in lung cancer.

Although targeted therapies often elicit profound initial patient responses, these effects are transient due to residual disease leading to acquired resistance. How tumors transition between drug responsiveness, tolerance and resistance, especially in the absence of preexisting subclones, remains unclear. In epidermal growth factor receptor (EGFR)-mutant lung adenocarcinoma cells, we demonstrate that residual disease and acquired resistance in response to EGFR inhibitors requires Aurora kinase A (AURKA) activity. Nongenetic resistance through the activation of AURKA by its coactivator TPX2 emerges in response to chronic EGFR inhibition where it mitigates drug-induced apoptosis. Aurora kinase inhibitors suppress this adaptive survival program, increasing the magnitude and duration of EGFR inhibitor response in preclinical models. Treatment-induced activation of AURKA is associated with resistance to EGFR inhibitors in vitro, in vivo and in most individuals with EGFR-mutant lung adenocarcinoma. These findings delineate a molecular path whereby drug resistance emerges from drug-tolerant cells and unveils a synthetic lethal strategy for enhancing responses to EGFR inhibitors by suppressing AURKA-driven residual disease and acquired resistance

The LRRK2 signalling system

The LRRK2 gene is a major contributor to genetic risk for Parkinson's disease and understanding the biology of the leucine-rich repeat kinase 2 (LRRK2, the protein product of this gene) is an important goal in Parkinson's research. LRRK2 is a multi-domain, multi-activity enzyme and has been implicated in a wide range of signalling events within the cell. Because of the complexities of the signal transduction pathways in which LRRK2 is involved, it has been challenging to generate a clear idea as to how mutations and disease associated variants in this gene are altered in disease. Understanding the events in which LRRK2 is involved at a systems level is therefore critical to fully understand the biology and pathobiology of this protein and is the subject of this review

Роль респираторных инфекций в обострениях бронхиальной астмы

Nineteen patients aged 18–65 years with moderate and severe exacerbations of atopic asthma were examined for respiratory viruses, Mycoplasma pneumoniae, and Chlamydophila pneumoniae. Interferon system, IL-4 and γ-IFN serum levels were also investigated. Viral infections (RS-virus, adenovirus, influenza types A (H1N1, H3N2) and B viruses, parainfluenza types 1 and 3 viruses) were diagnosed serologically or using PCR with direct detection of viral nucleic acids in 73.6 % of the patients. Diagnostic level of Mycoplasma pneumoniae antigen was found in 78.9 % of the patients, anti-Chlamydophila pneumoniae antibodies were detected in 31.6 %. Leukocyte interferon-producing function was decreased in all the patients.У 19 пациентов в возрасте 18–65 лет с атопической бронхиальной астмой во время тяжелых и среднетяжелых обострений проведено обследование на наличие респираторных вирусов, Mycoplasma pneumoniae и Chlamydophila pneumoniae, оценены состояние системы интерферона, уровни IL-4 и γ-IFN в сыворотке крови. У 73,6 % пациентов серологически или путем прямого выявления вирусных нуклеиновых кислот методом ПЦР подтверждено наличие вирусной инфекции (респираторно-синцитиальный вирус — РС-вирус, аденовирус, грипп А (H1N1, H3N2) и В, парагрипп 1-го и 3-го типа). У 78,9 % пациентов в сыворотке крови обнаружен антиген Mycoplasma pneumoniae в диагностически значимом титре, у 31,6 % пациентов — антитела к Chlamydophila pneumoniae. У всех пациентов отмечено выраженное снижение интерферон-продуцирующей способности лейкоцитов

Динамика выживаемости больных муковисцидозом в Москве и Московской области за периоды 1992–2001 и 2002–2011 гг.

Summary. The aim of this study was to evaluate changes in survival of patients with cystic fibrosis (CF) in Moscow and Moscow region and to determine factors influencing the survival. We analyzed outpatient medical records of patients followed-up in Moscow CF centers by the 1st of January, 2002, and by the 1st of January, 2012.Median survival for 2002–2012 was 37.2 years; this was significantly higher that the similar value for the previous decade (25.9 years). A total number of CF patients was more than doubled due to increased survival and improved diagnosis of the disease.Improved survival was due to improved work of CF centers and to implementation of effective medications, primarily dornase alfa (Pulmozyme) and some inhaled and systemic antibiotics and macrolides in subinhibitory concentrations, in routine clinical practice. Gram-negative infection, especially Burkholderia cepacia, was shown to decrease survival in CF patients in contrary to "mild" mutations that are better prognostic factors.Резюме. Целью работы явилось определение динамики числа и выживаемости больных муковисцидозом (МВ) в Москве и Московской области, а также определение факторов, влияющих на выживаемость. Были проанализированы амбулаторные карты больных, состоящих на учете в московских центрах муковисцидоза на 01.01.2002 и 01.01.2012.Медиана выживаемости больных за периоды 2002–2011 гг. составила 37,2 года, что достоверно выше, чем аналогичный показатель за предыдущее 10-летие – 25,9 года. Отмечено более чем 2-кратное увеличение общего количества больных, обусловленное ростом выживаемости и улучшением диагностики.Увеличение выживаемости обусловлено оптимизацией работы центров МВ и началом рутинного применения различных эффективных медикаментозных препаратов, прежде всего дорназы альфа (Пульмозим), а также некоторых ингаляционных и системных антибиотиков, макролидов в субингибирующих концентрациях. Показано, что инфицирование грамотрицательной инфекцией, особенно Burkholderia cepacia, снижает выживаемость пациентов с МВ, а наличие "мягкого" генотипа является более благоприятным прогностическим фактором

ИССЛЕДОВАНИЕ МЕХАНИЗМОВ НЕСТАБИЛЬНОСТИ ХАРАКТЕРИСТИК МДП-СТРУКТУР

The results of investigation are presented in the paper showing the influence of thermal processing on characteristics of MIS structures.Анотаці

The dynamics of innovation development for enterprises of the Republic of Tatarstan in the conditions of supply chain management and digital economy

© ExcelingTech Pub, UK. The strategic aim of the Russian economic progress is about transition to innovative development model by considering the digital economy and supply chain management. The main tasks of country government in program decisions are: organization of national innovative system and creating its infrastructure which provides technological modernization of economics, increasing of competitiveness based on hi-tech, transforming scientific potential into one of the main sources of sustained economic growth. The article presents an analysis of innovative activity dynamics in enterprises of the Republic of Tatarstan. The innovative activity of enterprises in the Republic was analyzed; indicators of shipped innovative products were viewed. The characteristics were given according to main indicators of transfer and commercialization of innovative technologies. The results of innovative activity in enterprises at the regional level were summarized