Tuberculosis (TB) is currently the leading cause of death among bacterial infectious diseases. The spectrum of disease manifestations depends on both host immune responses and the ability of Mycobacterium tuberculosis to resist it. Small non-coding RNAs are known to regulate gene expression; however, their functional role in the relationship of M. tuberculosis with the host is poorly understood. Here, we investigated the effect of small non-coding sRNAs MTS1338 and MTS0997 on M. tuberculosis properties by creating knockout strains. We also assessed the effect of small non-coding RNAs on the survival of wild type and mutant mycobacteria in primary cultures of human alveolar macrophages and the virulence of these strains in a mouse infection model. Wild-type and mutants survived differentially in human alveolar macrophages. Infection of I/St mice with KO M. tuberculosis H37RV strains provided beneficial effects onto major TB phenotypes. We observed attenuated tuberculosis-specific inflammatory responses, including reduced cellular infiltration and decreased granuloma formation in the lungs. Infections caused by KO strains were characterized by significantly lower inflammation of mouse lung tissue and increased survival time of infected animals. Thus, the deletion of MTS0997 and MTS1338 lead to a significant decrease in the virulence of M. tuberculosis.
Currently, endobronchial ultrasound dramatically changed diagnostic approaches for mediastinal lesions, both benign and malignant. Still there is a lack of data regarding the optimal anaesthesia, route of intubation, needle type, and specific clinical situations concerning EBUS in real clinical practice. A short, but clinically oriented, description of EBUS-TBNA and EUS-b-FNA techniques for mediastinal lesions is provided.
Sarcoidosis is a multi-organ granulomatosis of unknown origin. Modern diagnostic methods allow detecting this disease at an early stage. The absence of specific markers requires a comprehensive approach to diagnosis based on comparison of radiation, clinical, morphological and functional data. The course of sarcoidosis without damage to the respiratory system presents significant difficulties. It is extremely important to understand the time and means of starting Sarcoidosis’s treatment to avoid the early initiation of hormones and cytostatics and, on the other hand, to timely respond to progression and threatening conditions. Methods. Clinical recommendations are based on the analysis of Russian and English publications of the latest sarcoidosis research. The target audience of these clinical guidelines are therapists, general practitioners, pulmonologists, TB doctors, rheumatologists, dermatologists, radiation diagnosticians, immunologists, and clinical pharmacologists. Each thesis-recommendation for diagnosis and treatment is evaluated on an 1 to 5 scale of levels of evidence and an A, B, C scale of the grades of recommendations. The clinical guidelines also contain comments and explanations for the theses-recommendations, diagnostic algorithms, treatment strategies, reference materials on the use of recommended drugs. Conclusion. Current information on epidemiology, clinical manifestations, diagnosis and management strategies for patients with sarcoidosis are covered in the presented clinical guidelines. Approved by the decision of the Scientific and Practical Council of the Ministry of Health of the Russian Federation (2022).
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