Impact of tuberculosis treatment length and adherence under different transmission intensities

Fundacao de Amparo a Pesquisa do Estado da Bahia-FAPESB (PNX 0006/2009); Conselho Nacional de Desenvolvimento Cientifico e Tecnologico-CNPq (410498/2006-8); Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior-CAPES and Fundacao para a Ciencia e a Tecnologia-FCT (AUX-PE-FCT 1171/2009); European Commission (EC-ICT-231807); INCT-Citecs (57386/2008-9); National Institutes of Science and Technology Programme (MCT-CNPq, Brazil); Fundacao para a Ciencia e Tecnologia (PEst-OE/MAT/UIO297/2014; EXPL/MAT-CAL/0794/2013); FAPESB (B0L0143/2008)Tuberculosis(TB) is a leading cause of human mortality due to infectious disease.Treatmentdefault is a relevant factor which reduces therapeutic success and increases the risk of resistant TB. In this work we analyze the relation betweentreatmentdefault andtreatmentlengthalong with its consequence on the disease spreading. We use a stylized model structure to explore, systematically, the effects of varyingtreatmentduration and compliance. We find that shorteningtreatmentalone may not reduce TB prevalence, especially in regions wheretransmissionintensity is high, indicating the necessity of complementing this action with increased compliance. A family of default functions relating the proportion of defaulters to thetreatmentlengthis considered and adjusted to a particular dataset. We find that the epidemiological benefits of shortertreatmentregimens are tightly associated with increases intreatmentcompliance and depend on the epidemiological background.authorsversionpublishe

Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field