Standardization of the collection of exhaled breath condensate and exhaled breath aerosol using a feedback regulated sampling device

Exhaled breath condensate (EBC) and associated exhaled breath aerosols (EBA) are valuable non-invasive biological media used for the quantification of biomarkers. EBC contains exhaled water vapor, soluble gas-phase (polar) organic compounds, ionic species, plus other species including semi- and non-volatile organic compounds, proteins, cell fragments, DNA, dissolved inorganic compounds, ions, and microbiota (bacteria and viruses) dissolved in the co-collected EBA. EBC is collected from subjects who breathe 'normally' through a chilled tube assembly for approximately 10 min and is then harvested into small vials for analysis. Aerosol filters without the chilled tube assembly are also used to separately collect EBA. Unlike typical gas-phase breath samples used for environmental and clinical applications, the constituents of EBC and EBA are not easily characterized by total volume or carbon dioxide (CO2) concentration, because the gas-phase is vented. Furthermore, EBC and associated EBA are greatly affected by breathing protocol, more specifically, depth of inhalation and expelled breath velocity. We have tested a new instrument developed by Loccioni Gruppa Humancare (Ancona, Italy) for implementation of EBC collection from human subjects to assess EBC collection parameters. The instrument is the first EBC collection device that provides instantaneous visual feedback to the subjects to control breathing patterns. In this report we describe the operation of the instrument, and present an overview of performance and analytical applications

Application of evidence-based methods to construct mechanism-driven chemical assessment frameworks

The workshop titled “Application of evidence-based methods to construct mechanism-driven chemical assessment frameworks” was co-organized by the Evidence-based Toxicology Collaboration and the European Food Safety Authority (EFSA) and hosted by EFSA at its headquarters in Parma, Italy on October 2 and 3, 2019. The goal was to explore integration of systematic review with mechanistic evidence evaluation. Participants were invited to work on concrete products to advance the exploration of how evidence-based approaches can support the development and application of adverse outcome pathways (AOP) in chemical risk assessment. The workshop discussions were centered around three related themes: 1) assessing certainty in AOPs, 2) literature-based AOP development, and 3) integrating certainty in AOPs and non-animal evidence into decision frameworks. Several challenges, mostly related to methodology, were identified and largely determined the workshop recommendations. The workshop recommendations included the comparison and potential alignment of processes used to develop AOP and systematic review methodology, including the translation of vocabulary of evidence-based methods to AOP and vice versa, the development and improvement of evidence mapping and text mining methods and tools, as well as a call for a fundamental change in chemical risk and uncertainty assessment methodology if to be conducted based on AOPs and new approach methodologies (NAM). The usefulness of evidence-based approaches for mechanism-based chemical risk assessments was stressed, particularly the potential contribution of the rigor and transparency inherent to such approaches in building stakeholders’ trust for implementation of NAM evidence and AOPs into chemical risk assessment

Applying evidence-based methods to the development and use of adverse outcome pathways

The workshop “Application of evidence-based methods to construct mechanistic frameworks for the development and use of non-animal toxicity tests” was organized by the Evidence-based Toxicology Collaboration and hosted by the Grading of Recommendations Assessment, Development and Evaluation Working Group on June 12, 2019. The purpose of the workshop was to bring together international regulatory bodies, risk assessors, academic scientists, and industry to explore how systematic review methods and the adverse outcome pathway framework could be combined to develop and use mechanistic test methods for predicting the toxicity of chemical substances in an evidence-based manner. The meeting covered the history of biological frameworks, the way adverse outcome pathways are currently developed, the basic principles of systematic methodology, including systematic reviews and evidence maps, and assessment of certainty in models, and adverse outcome pathways in particular. Specific topics were discussed via case studies in small break-out groups. The group concluded that adverse outcome pathways provide an important framework to support mechanism-based assessment in environmental health. The process of their development has a few challenges that could be addressed with systematic methods and automation tools. Addressing these challenges will increase the transparency of the evidence behind adverse outcome pathways and the consistency with which they are defined; this in turn will increase their value for supporting public health decisions. It was suggested to explore the details of applying systematic methods to adverse outcome pathway development in a series of case studies and workshops

RECENT DEVELOPMENTS IN IONIC LIQUIDS AND NANOMATERIALS

In this paper, the development of Ionic Liquids to synthesize various types of nanoparticles having commercial and viable uses in 21st century is discussed. Nanotechnology is a promising methodology that generates various types of nanoparticles. Research-based on Ionic Liquids is in the progressive stage and by amalgamating it in nanotechnology, amazing results can be accomplished. Thus, efforts must be made to develop advanced techniques to synthesize nanoparticles with desired structures and morphologies in eco-friendly and sustainable Ionic Liquids to reduce environmental pollution in the future. With this perspective, various developments and efforts made by the scientists in the domain of Nanomaterials and Ionic Liquids have been reviewed.</jats:p

Catalytic transformations via metallocarbenes

This thesis describes a new catalytic activity of a commonly used metathesis catalyst and demonstrates the viability of directly coupling two powerful C-C bond forming strategies: cross-metathesis and ylide transformations, both proceeding via metal-catalysed carbene transfer. Catalytic C-C bond formation reactions are highly significant; my studies focus on such transformations involving metallocarbenes. Grubbs' 2nd generation Ru catalyst is the most commonly used catalyst in olefin metathesis to generate thermodynamically preferred trans-olefms. During the course of my studies, I established that Grubbs 2nd generation catalyst (0.5 mol%) can also dimerise diazoacetates to give cis-enediesters (maleates) in good to excellent yields (74-99%) with high stereoselectivity (Z:E>95:5). The reaction between two different diazoacetates, catalysed by Grubbs catalyst gave access to unsymmetrical cis-enediesters with high stereoselectivity (Z:E>95:5, generally 99:1). The catalyst was found to retain its alkene metathetical activity during diazo coupling; building on this latter observation a novel route to access dienyl dilactones by head-to-head dimerisation of unsaturated diazoacetates was developed. Cross-metathesis was found to be chemoselective in the presence of diazo functionality (when flanked by two carbonyl groups), allowing the functionalisation of tethered olefin. The elaborated diazocarbonyl olefms were subjected to Rh2(OAc)4 catalysed ylide formation and subsequent transformations. Significantly, one-pot cross-metathesis/ylide transformations (1,3-dipolar cycloaddition and [2,3]-simgatropic rearrangement) also proved to be viable, establishing that the spent Ru catalyst following metathesis does not affect the subsequent Rh(II)-catalysed transformation.</p