Insights into Chagas treatment based on the potential of bacteriocin AS-48

Chagas disease caused by the protozoan parasite Trypanosoma cruzi represents a significant public health problem in Latin America, affecting around 8 million cases worldwide. Nowadays is urgent the identification of new antichagasic agents as the only therapeutic options available, Nifurtimox and Benznidazole, are in use for>40 years, and present high toxicity, limited efficacy and frequent treatment failures in the chronic phase of the disease. Recently, it has been described the antiparasitic effect of AS-48, a bacteriocin produced by Enterococcus faecalis, against Trypanosoma brucei and Leishmania spp. In this work, we have demonstrated the in vitro potential of the AS-48 bacteriocin against T. cruzi. Interesting, AS-48 was more effective against the three morphological forms of different T. cruzi strains, and displayed lower cytotoxicity than the reference drug Benznidazole. In addition, AS-48 combines the criteria established as a potential antichagasic agent, resulting in a promising therapeutic alternative. According to the action mechanism, AS-48 trypanocidal activity could be explained in a mitochondrion-dependent manner through a reactive oxygen species production and mitochondrial depolarization, causing a fast and severe bioenergetic collapse.This work was supported by the Spanish Ministry of Economy and Competitiveness [grant numbers SAF2013-48971-C2-1-R, CSD2010- 00065], both including funds from the European Regional Development Fundings (ERDF), and the Ministry of Education of Spain [RM-E, grant number FPU14/01537]

Outcomes from elective colorectal cancer surgery during the SARS-CoV-2 pandemic

This study aimed to describe the change in surgical practice and the impact of SARS-CoV-2 on mortality after surgical resection of colorectal cancer during the initial phases of the SARS-CoV-2 pandemic

Nanoparticles-A Thoracic Toxicology Perspective

A substantial literature demonstrates that the main ultrafine particles found in ambient urban air are combustion-derived nanoparticles (CDNP) which originate from a number of sources and pose a hazard to the lungs. For CDNP, three properties appear important-surface area, organics and metals. All of these can generate free radicals and so induce oxidative stress and inflammation. Inflammation is a process involved in the diseases exhibited by the individuals susceptible to the effects of PM-development and exacerbations of airways disease and cardiovascular disease. It is therefore possible to implicate CDNP in the common adverse effects of increased PM. The adverse effects of increases in PM on the cardiovascular system are well-documented in the epidemiological literature and, as argued above, these effects are likely to be driven by the combustion-derived NP. The epidemiological findings can be explained in a number of hypotheses regarding the action of NP:-1) Inflammation in the lungs caused by NP causes atheromatous plaque development and destabilization; 2) The inflammation in the lungs causes alteration in the clotting status or fibrinolytic balance favouring thrombogenesis; 3) The NP themselves or metals/organics released by the particles enter the circulation and have direct effects on the endothelium, plaques, the clotting system or the autonomic nervous system/ heart rhythm. Environmental nanoparticles are accidentally produced but they provide a toxicological model for a new class of purposely 'engineered' NP arising from the nanotechnology industry, whose effects are much less understood. Bridging our toxicological knowledge between the environmental nanoparticles and the new engineered nanoparticles is a considerable challenge

Sharing and community curation of mass spectrometry data with Global Natural Products Social Molecular Networking

The potential of the diverse chemistries present in natural products (NP) for biotechnology and medicine remains untapped because NP databases are not searchable with raw data and the NP community has no way to share data other than in published papers. Although mass spectrometry techniques are well-suited to high-throughput characterization of natural products, there is a pressing need for an infrastructure to enable sharing and curation of data. We present Global Natural Products Social molecular networking (GNPS, http://gnps.ucsd.edu), an open-access knowledge base for community wide organization and sharing of raw, processed or identified tandem mass (MS/MS) spectrometry data. In GNPS crowdsourced curation of freely available community-wide reference MS libraries will underpin improved annotations. Data-driven social-networking should facilitate identification of spectra and foster collaborations. We also introduce the concept of ‘living data’ through continuous reanalysis of deposited data

Verification of second-order effects in slender reinforced masonry walls

Previous experimental and numerical works have demonstrated the effectiveness of reinforced masonry (RM) walls in tall single-storey wide-span buildings. Nevertheless, to date, EN1996 does not have a consistent approach to checking the second-order effects due to out-of-plane loads in such structures, and requirements for RM walls are too restrictive. New fibre models have been calibrated on the basis of the above tests and used to carry out parametric pushover analyses to study the influence of wall slenderness, roof vertical load and the percentage of vertical reinforcement on the out-of-plane behaviour of tall RM walls. In this numerical study, new slenderness limits for the safe use of this construction technology are defined, above which second-order moments must be calculated or failures due to instability become predominant, overcoming the shortcomings of current standards. This work also proposes and calibrates some rational approaches for evaluating second-order effects in tall RM walls, based on model column (MC) and nominal curvature (NC) methods. The reliability of the two simplified design methods is checked against the results of the above numerical models. MC method provides the best results, without limitations on the type of failure of the section (i.e. \u2018balanced\u2019, as for NC method), with errors usually lower than 25% and always conservative

Strengthening of in-plane and out-of-plane capacity of thin clay masonry infills using textile- And fiber-reinforced mortar

This paper presents an overview of the experimental results obtained by combined in-plane/out-of-plane (IP/OOP) tests carried out on reinforced concrete (RC) frames infilled with thin clay masonry walls. After preliminary characterization tests on building materials, combined IP/OOP tests on eight full-scale, one-bay, one-story infilled RC frames were carried out. Three external strengthening solutions were investigated considering three types of lime-based plasters, reinforced by means of dispersed fibers and/or bidirectional basalt meshes, applied on both sides of each wall. The experimental results of the tested frames are presented, discussed, and compared to evaluate the performance and the effectiveness of each strengthening solution

Combined in-plane and out-of-plane seismic effects on masonry infills in RC frames

Unreinforced masonry (URM) infills, classified as non-structural elements and often neglected in design models, highly affect the seismic behaviour of RC frames increasing the global structural stiffness; furthermore, the in-plane (IP) damage of panels highly reduces their out-of-plane (OOP) resistance, anticipating soft-floor mechanisms. This paper presents a FE macro-model to simultaneously simulate the IP-OOP infill behaviour, calibrated for two different types of URM panel using experimental results. The goal is to investigate the seismic response of RC infilled frames considering earthquake directional effects. Nonlinear static analyses with different load-pattern directions are performed on traditionally and seismically designed frames. Results are presented using pushover curves, ductility indexes and resistant Peak Ground Acceleration associated to the achievement of infill and frame Limit States. IP/OOP interaction considerably affects both the global resistance and the infill Limit States in case of thin panel, and the frame Ultimate Limit State in case of thick panel

Masonry arch bridges fragility assessment

Masonry arch bridges still represent a crucial element of the railway transportation network across Europe, but their exposition to seismic hazard has not been currently exploited as for the other bridge typologies. The paper deals with seismic vulnerability assessment of existing single-span masonry arch bridges following the principles of limit analysis. An iterative procedure is implemented to define the capacity curve through a non linear Kinematic analysis. The process involves the determination of the collapse mechanism depending on geometrical features, the hinges location, the collapse multiplier and the thrust line. Seismic fragility curves for generalized classes of railway masonry bridges are subsequently obtained considering the effective ranges of main geometric and material parameters affecting the arch bridge capacity. The intrinsic variability of the seismic action is incorporated through a set of ground motions compatible with EC8 spectra for different types of soil, with PGA varying in the range of 0.05-1.5g. The fragility curves obtained represent an useful tool to plan retrofit interventions on stock of existing masonry bridges

Seismic vulnerability assessment of single span masonry arch bridges

Masonry arch bridges still represent a crucial element of the railway transportation network across Europe, but their exposition to seismic hazard has not been currently exploited as for the other bridge typologies. The paper deals with seismic vulnerability assessment of existing single-span masonry arch bridges following the principles of limit analysis. An iterative procedure is implemented to define the capacity curve through a non linear kinematic analysis. The process involves the determination of the collapse mechanism depending on geometrical features, the hinges location, the collapse multiplier and the thrust line. The intrinsic variability of the seismic action is incorporated through a set of ground motions compatible with EC8 spectra for different types of soil, with PGA varying in the range of 0.05-1.5g. Seismic fragility curves for generalized classes of railway masonry bridges are subsequently obtained considering the effective ranges of main geometric and material parameters affecting the arch bridge capacity