PLA/PCL electrospun membranes of tailored fibres diameter as drug delivery systems

[EN] The main electrospinning parameters, i.e., polymer concentration in the injectable solution, solvents used and their proportion, flow rate, voltage and distance to collector were herein systematically modified to analyse their particular influence in fibres diameter of electrospun membranes of poly(lactic acid), polycaprolactone and their mixture. As a result of this analysis, the procedures to obtain membranes of these polymers and blend with under- and above-micron-sized fibres were established, in which the solvents ratio (chloroform/methanol and dichloromethane/dimethylformamide) and voltage were found to play the major role. Moreover, the plausible differential effect of these fibres diameters (0.8 and 1.8 ¿m) in the controlled release of a molecule of interest was explored, using bovine serum albumin (BSA), proving that the most effective configuration for BSA release among those studied was the PLA-PCL combination in membranes of above-micron fibres diameter.The authors acknowledge Spanish Ministerio de Economia y Competitividad through DPI2015-65401-C3-2-R project, and the assistance and advice of the Electron Microscopy Service of the Universitat Politecnica de Valencia (Spain).Herrero-Herrero, M.; Gómez-Tejedor, J.; Vallés Lluch, A. (2018). PLA/PCL electrospun membranes of tailored fibres diameter as drug delivery systems. European Polymer Journal. 99:445-455. https://doi.org/10.1016/j.eurpolymj.2017.12.045S4454559

How can natural products serve as a viable source of lead compounds for the development of new/novel anti-malarials?

Malaria continues to be an enormous global health challenge, with millions of new infections and deaths reported annually. This is partly due to the development of resistance by the malaria parasite to the majority of established anti-malarial drugs, a situation that continues to hamper attempts at controlling the disease. This has spurred intensive drug discovery endeavours geared towards identifying novel, highly active anti-malarial drugs, and the identification of quality leads from natural sources would greatly augment these efforts. The current reality is that other than compounds that have their foundation in historic natural products, there are no other compounds in drug discovery as part of lead optimization projects and preclinical development or further that have originated from a natural product start-point in recent years. This paper briefly presents both classical as well as some more modern, but underutilized, approaches that have been applied outside the field of malaria, and which could be considered in enhancing the potential of natural products to provide or inspire the development of anti-malarial lead compounds

Organizing risk: organization and management theory for the risk society

Risk has become a crucial part of organizing, affecting a wide range of organizations in all sectors. We identify, review and integrate diverse literatures relevant to organizing risk, building on an existing framework that describes how risk is organized in three ‘modes’ – prospectively, in real-time, and retrospectively. We then identify three critical issues in the existing literature: its fragmented nature; its neglect of the tensions associated with each of the modes; and its tendency to assume that the meaning of an object in relation to risk is singular and stable. We provide a series of new insights with regard to each of these issues. First, we develop the concept of a risk cycle that shows how organizations engage with all three modes and transition between them over time. Second, we explain why the tensions have been largely ignored and show how studies using a risk work perspective can provide further insights into them. Third, we develop the concept of risk translation to highlight the ways in the meanings of risks can be transformed and to identify the political consequences of such translations. We conclude the paper with a research agenda to elaborate these insights and ideas further

Antischistosomal Activity of Trioxaquines: In Vivo Efficacy and Mechanism of Action on Schistosoma mansoni

Schistosomiasis is among the most neglected tropical diseases, since its mode of spreading tends to limit the contamination to people who are in contact with contaminated waters in endemic countries. Here we report the in vitro and in vivo anti-schistosomal activities of trioxaquines. These hybrid molecules are highly active on the larval forms of the worms and exhibit different modes of action, not only the alkylation of heme. The synergy observed with praziquantel on infected mice is in favor of the development of these trioxaquines as potential anti-schistosomal agents

Advances in heterometallic ring-opening (co)polymerisation catalysis

Truly sustainable plastics require renewable feedstocks coupled with efficient production and end-of-life degradation/recycling processes. Some of the most useful degradable materials are aliphatic polyesters, polycarbonates and polyamides, which are often prepared via ring-opening (co)polymerisation (RO(CO)P) using an organometallic catalyst. While there has been extensive research into ligand development, heterometallic cooperativity offers an equally promising yet underexplored strategy to improve catalyst performance, as heterometallic catalysts often exhibit significant activity and selectivity enhancements compared to their homometallic counterparts. This review describes advances in heterometallic RO(CO)P catalyst design, highlighting the overarching structure-activity trends and reactivity patterns to inform future catalyst design

High activity of an indium alkoxide complex toward ring opening polymerization of cyclic esters

An indium complex supported by a ferrocene-derived Schiff base ligand has an unprecedented high activity toward ε-caprolactone, δ-valerolactone, and β-butyrolactone. l-Lactide, d,l-lactide, and trimethylene carbonate polymerizations also showed moderate to high activity

Les décisions face aux risques majeurs : retours d’expériences et pistes d’amélioration

This paper attempts to share some lessons learned by practitioners and researchers studying challenges of decision-making in the domain of major risks, either technological, natural or health diseases. Varying regulatory frameworks, different decision-making levels and scientific disciplines lead to a diversity of approaches which complicates the design of generic principles for decision-aiding for the prevention of low probability-high consequence events. In order to delineate the potential for improvement, several biases affecting prevention are addressed (in risk modelling and risk perception, especially of low probabilities). The proposed approach focuses on the analysis and quality assurance of the conditions of validity and legitimacy of decisions, implying several stakeholders and suggests the need for a better use of case studies.Cet article est l’occasion pour nous de partager certains enseignements acquis par les praticiens et les chercheurs étudiant les défis de la prise de décision dans le domaine des risques majeurs, qu’ils soient technologiques, naturels ou sanitaires. Des différences dans les cadres réglementaires, dans les niveaux et les objets de décisions, dans les cadres disciplinaires fondent une diversité d’approches ce qui complique la conception d’un dispositif générique d’aide à la décision pour la prévention de ces événements rares et catastrophiques. Afin de situer des axes de progrès, de multiples biais affectant celles-ci sont évoqués (dans la modélisation du risque, dans la perception du risque et des faibles probabilités). L’approche proposée vise à fournir des éléments de réponses en vue de l’analyse et de la fiabilisation des conditions de validité et de légitimité des décisions, impliquant de multiples parties prenantes et plaide pour un usage renforcé des études de cas

Lessons Learned from Toulouse and Buncefield Disasters: From Risk Analysis Failures to the Identification of Atypical Scenarios Through a Better Knowledge Management

The recent occurrence of severe major accidents has brought to light flaws and limitations of hazard identification (HAZID) processes performed for safety reports, as in the accidents at Toulouse (France) and Buncefield (UK), where the accident scenarios that occurred were not captured by HAZID techniques. The present study focuses on this type of atypical accident scenarios deviating from normal expectations. The main purpose is to analyse the examples of atypical accidents mentioned and to attempt to identify them through the application of a well known methodology such as the bow-tie analysis. To these aims, the concept of atypical event is accurately defined. Early warnings, causes, consequences and occurrence mechanisms of the specific events are widely studied and general failures of risk assessment, management and governance isolated. These activities contribute to outline a set of targeted recommendations, addressing transversal common deficiencies and also demonstrating how a better management of knowledge from the study of past events can support future risk assessment processes in the identification of atypical accident scenarios. Thus, a new methodology is not suggested, rather a specific approach coordinating a more effective use of experience and available information is described, in order to suggest that lessons to be learned from past accidents can be effectively translated into actions of prevention