Cross-country migration linked to people who inject drugs challenges the long-term impact of national HCV elimination programmes

To the Editor: As of 2018, the majority of Western European countries – including Spain – have lifted restrictions to therapy based on disease severity in the context of HCV infections.1 Long overdue, most national elimination programmes now also include access to care for people who inject drugs (PWID), 2 who are at the core of ongoing HCV transmission.3 Macías et al.4 have recently shown in this Journal that high viral cure rates can be achieved in this group, hereby providing evidence that targeting PWID in treatment programmes is worthwhile. However, the extent to which such national efforts can reduce the HCV burden not only depends on the uptake into care and treatment success rates, it is also determined by the relative importance of within-country transmission and virus importation from elsewhere. As the chronic nature of most HCV infections hampers reliably reconstructing contact networks from patient interviews, virus genetic data can be a valuable alternative source of information for elucidating the geographic history of virus lineages (e.g. [5], [6]). Using such data, we have recently shown that for the most prevalent subtype among PWID in Spain (40%, 7), HCV1a, infections often link to infections abroad – in recent years >50% link to Western European countries, mostly European Union (EU) member states – as opposed to other infections ..

Dominant Negative Mutants of Bacillus thuringiensis Cry1Ab Toxin Function as Anti-Toxins: Demonstration of the Role of Oligomerization in Toxicity

BACKGROUND:Bacillus thuringiensis Cry toxins, that are used worldwide in insect control, kill insects by a mechanism that depends on their ability to form oligomeric pores that insert into the insect-midgut cells. These toxins are being used worldwide in transgenic plants or spray to control insect pests in agriculture. However, a major concern has been the possible effects of these insecticidal proteins on non-target organisms mainly in ecosystems adjacent to agricultural fields. METHODOLOGY/PRINCIPAL FINDINGS:We isolated and characterized 11 non-toxic mutants of Cry1Ab toxin affected in different steps of the mechanism of action namely binding to receptors, oligomerization and pore-formation. These mutant toxins were analyzed for their capacity to block wild type toxin activity, presenting a dominant negative phenotype. The dominant negative phenotype was analyzed at two levels, in vivo by toxicity bioassays against susceptible Manduca sexta larvae and in vitro by pore formation activity in black lipid bilayers. We demonstrate that some mutations located in helix alpha-4 completely block the wild type toxin activity at sub-stoichiometric level confirming a dominant negative phenotype, thereby functioning as potent antitoxins. CONCLUSIONS/SIGNIFICANCE:This is the first reported case of a Cry toxin dominant inhibitor. These data demonstrate that oligomerization is a fundamental step in Cry toxin action and represent a potential mechanism to protect special ecosystems from the possible effect of Cry toxins on non-target organisms

Prevalence of Anxiety and Depression among Outpatients with Type 2 Diabetes in the Mexican Population

Depression and anxiety are common in diabetic patients; however, in recent years the frequency of these symptoms has markedly increased worldwide. Therefore, it is necessary to establish the frequency and factors associated with depression and anxiety, since they can be responsible for premature morbidity, mortality, risk of developing comorbidities, complications, suffering of patients, as well as escalation of costs. We studied the frequency of depression and anxiety in Mexican outpatients with type 2 diabetes and identified the risk factors for depression and anxiety.We performed a study in 820 patients with type 2 diabetes. The prevalence of depression and anxiety was estimated using the Hamilton Depression Rating Scale and the Hamilton Anxiety Rating Scale, respectively. We calculated the proportions for depression and anxiety and, after adjusting for confounding variables, we performed multivariate analysis using multiple logistic regressions to evaluate the combined effect of the various factors associated with anxiety and depression among persons with type 2 diabetes. The rates for depression and anxiety were 48.27% (95% CI: 44.48–52.06) and 55.10% (95% CI: 51.44–58.93), respectively. Occupation and complications in diabetes were the factors associated with anxiety, whereas glucose level and complications in diabetes were associated with depression. Complications in diabetes was a factor common to depression and anxiety (p<0.0001; OR 1.79, 95% CI 1.29–2.4).Our findings demonstrate that a large proportion of diabetic patients present depression and/or anxiety. We also identified a significant association between complications in diabetes with depression and anxiety. Interventions are necessary to hinder the appearance of complications in diabetes and in consequence prevent depression and anxiety

Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)1.

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

The Mars Environmental Dynamics Analyzer, MEDA. A Suite of Environmental Sensors for the Mars 2020 Mission

86 pags, 49 figs, 24 tabsNASA's Mars 2020 (M2020) rover mission includes a suite of sensors to monitor current environmental conditions near the surface of Mars and to constrain bulk aerosol properties from changes in atmospheric radiation at the surface. The Mars Environmental Dynamics Analyzer (MEDA) consists of a set of meteorological sensors including wind sensor, a barometer, a relative humidity sensor, a set of 5 thermocouples to measure atmospheric temperature at ∼1.5 m and ∼0.5 m above the surface, a set of thermopiles to characterize the thermal IR brightness temperatures of the surface and the lower atmosphere. MEDA adds a radiation and dust sensor to monitor the optical atmospheric properties that can be used to infer bulk aerosol physical properties such as particle size distribution, non-sphericity, and concentration. The MEDA package and its scientific purpose are described in this document as well as how it responded to the calibration tests and how it helps prepare for the human exploration of Mars. A comparison is also presented to previous environmental monitoring payloads landed on Mars on the Viking, Pathfinder, Phoenix, MSL, and InSight spacecraft.This work has been funded by the Spanish Ministry of Economy and Competitiveness, through the projects No. ESP2014-54256-C4-1-R (also -2-R, -3-R and -4-R) and AYA2015-65041-P; Ministry of Science, Innovation and Universities, projects No. ESP2016-79612-C3-1-R (also -2-R and -3-R), ESP2016-80320-C2-1-R, RTI2018-098728-B-C31 (also -C32 and -C33) and RTI2018-099825-B-C31; Instituto Nacional de Tecnica Aeroespacial; Ministry of Science and Innovation's Centre for the Development of Industrial Technology; Grupos Gobierno Vasco IT1366-19; and European Research Council Consolidator Grant no 818602.Peer reviewe

Nurses' perceptions of aids and obstacles to the provision of optimal end of life care in ICU

Contains fulltext : 172380.pdf (publisher's version ) (Open Access