The Role of the Novel Exopolyphosphatase MT0516 in Mycobacterium tuberculosis Drug Tolerance and Persistence

Inorganic polyphosphate (poly P) has been postulated to play a regulatory role in the transition to bacterial persistence. In bacteria, poly P balance in the cell is maintained by the hydrolysis activity of the exopolyphosphatase PPX. However, the Mycobacterium tuberculosis PPX has not been characterized previously. Here we show that recombinant MT0516 hydrolyzes poly P, and an MT0516-deficient M. tuberculosis mutant exhibits elevated intracellular levels of poly P and increased expression of the genes mprB, sigE, and rel relative to the isogenic wild-type strain, indicating poly P-mediated signaling. Deficiency of MT0516 resulted in decelerated growth during logarithmic-phase in axenic cultures, and tolerance to the cell wall-active drug isoniazid. The MT0516-deficient mutant showed a significant survival defect in activated human macrophages and reduced persistence in the lungs of guinea pigs. We conclude that exopolyphosphatase is required for long-term survival of M. tuberculosis in necrotic lung lesions

Relation between health literacy, self-care and adherence to treatment with oral anticoagulants in adults: a narrative systematic review.

Background Oral anticoagulants (OAC) are widely used in patients with cardiovascular diseases. However, for optimal OAC self-care patients must have skills, among which health literacy (HL) is highlighted. We aimed to describe the relation between HL and self-care in cardiovascular patients on OAC treatment. Methods Electronic searches were carried out in the PubMed, Scopus, Embase, CINAHL, Web of Science, Cochrane Library, SciELO, IME-Biomedicina, CUIDEN Plus and LILACS databases, limited to Spanish and English language and between January 2000-December 2016. Papers reported on adults older than 18 years, taking OAC by themselves for at least three months. PRISMA guidelines were used for paper selection. Results We identified 142 articles and finally included 10; almost all of them about warfarin. Our results suggest that in patients taking OAC treatments there is a positive relationship between HL and the level of knowledge. In addition, a small percentage of participants on the selected papers recognized the side effects and complications associated with OAC treatment. Lower HL level was associated with greater knowledge deficits and less adherence to treatment. Conclusion There is a paucity of research evaluating the effect of HL on diverse aspects of OAC treatments. There is a need to expand the evidence base regarding appropriate HL screening tools, determinants of adequate knowledge and optimal behaviours related to OAC self-management

Assessment of endogenous fibrinolysis in clinical using novel tests - Ready for clinical roll-out?

© The Author(s) 2021. This article is licensed under a Creative Commons Attribution 4.0 International License. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.The occurrence of thrombotic complications, which can result in excess mortality and morbidity, represent an imbalance between the pro-thrombotic and fibrinolytic equilibrium.The mainstay treatment of these complications involves the use of antithrombotic agents but despite advances in pharmacotherapy, there remains a significant proportion of patients who continue to remain at risk.Endogenous fibrinolysis is a physiological counter-measure against lasting thrombosis and may be measured using several techniques to identify higher risk patients who may benefit from more aggressive pharmacotherapy. However, the assessment of the fibrinolytic systemis not yet accepted into routine clinical practice.In this review, we will revisit the different methods of assessing endogenous fibrinolysis (factorial assays, turbidimetric lysis assays, viscoelastic and the global thrombosis tests), including the strengths, limitations, correlation to clinical outcomes of each method and howwe might integrate the assessment of endogenous fibrinolysis into clinical practice in the future.Peer reviewedFinal Published versio