Development and Implementation of an e-Trigger Tool for Adverse Drug Events in a Swiss University Hospital.

Purpose: The purpose of the study was to develop and implement an institution-specific trigger tool based on the Institute for Healthcare Improvement medication module trigger tool (IHI MMTT) in order to detect and monitor ADEs.

Methods: We performed an investigator-driven, single-center study using retrospective and prospective patient data to develop ("development phase") and implement ("implementation phase") an efficient, institution-specific trigger tool based on the IHI MMTT. Complete medical data from 1008 patients hospitalized in 2018 were used in the development phase.

The tox is in the detail: technical fundamentals for designing, performing, and interpreting experiments on toxicity of microplastics and associated substances.

Over the last 10 years, there has been a plethora of experimental studies estimating the potential of microplastic particles (MPs) to exert toxic effects in the environment, many specifically focusing on their postulated capacity to enhance the transfer of environmental pollutants into organisms after ingestion. Obviously, there is little to no consensus on appropriate experimental design, which is mainly owing to the novelty, the interdisciplinarity of the subject, and the complexity of parameters involved. This results in fundamental discrepancies regarding the materials applied, the approach for spiking MPs with pollutants, and the exact exposure scenario.

Microplastic particles reduce EROD-induction specifically by highly lipophilic compounds in RTL-W1 cells.

Microplastic particles (MPs) from lipophilic polymers have been shown to efficiently accumulate hydrophobic organic contaminants (HOCs) in aquatic environments. MPs have, therefore, frequently been discussed as vectors for contaminants, enhancing HOC uptake by various organisms after ingestion followed by pollutant release; however, integrative models of sorption argue against this mechanism and even predict cleansing of pollutants from biological systems under particular circumstances. In order to experimentally investigate such a depuration mechanism, RTL-W1 cells were dosed with three 7-ethoxyresorufin-O-deethylase (EROD) inducers of distinct lipophilicity via the medium before adding both native and hexane-purified polyethylene MPs (20-25 μm) to the medium surface.

Effect of pH on the toxicity of fumonisins towards the RTL-W1 cell line and zebrafish (Danio rerio) embryos.

Fumonisins are common contaminants of maize. The neutral red assay, using the RTL-W1 trout liver cell line, and the fish embryo test (FET), using zebrafish, were selected to assess the effect of pH on the cytotoxicity, acute toxicity and teratogenicity of fumonisin B (FB). The results demonstrated that FB exerts low cytotoxicity towards RTL-W1 cells without pH adjustment (IC 1 746 μM), and no cytotoxicity after pH-adjustment to physiological conditions.

Bioavailability of microplastic-bound pollutants in vitro: The role of adsorbate lipophilicity and surfactants.

The potential role of microplastic particles (MPs) as vectors for lipophilic organic pollutants enhancing their uptake by organisms has repeatedly been discussed in the scientific community. Likewise, several studies indicate an important role of surfactants in pollutant-transfer from MP to organisms. Employing polyethylene particles, the bioavailability of three MP-bound inducers of 7-ethoxyresorufin-O-deethylase (EROD) with variable lipophilicity was quantitatively compared via EROD activity in RTL-W1 cells.

Microplastic testing in vitro: Realistic loading of pollutants, surfactant-free solid surface-dosing and bioanalytical detection using a sensitivity-optimized EROD assay.

Microplastic particles (MPs) are emerging contaminants in aquatic environments, which are assumed to play a role as vectors for lipophilic pollutants, as the particles bear a potential for the accumulation of lipophilic contaminants from the water phase on the MPs' surface and subsequent release in contact with organisms. In an attempt to allow the bioanalytical detection and quantitatively estimate bioavailability of MP-bound pollutants under realistic conditions in vitro, a protocol was developed for water-based loading of lipophilic substances to MPs using a solid-phase extraction (SPE) approach and subsequent detection of the substances in a sensitivity-enhanced 7-ethoxyresorufin-O-deethylase (EROD) assay with RTL-W1 cells. Exemplarily, particles were loaded with benzo[k]fluoranthene (BkF), which was shown to bind to MPs with high affinity.

Genetically engineered zebrafish liver (ZF-L) cells as an in vitro source for zebrafish acetylcholinesterase (zfAChE) for the use in AChE inhibition assays.

Zebrafish acetylcholinesterase (zfAChE) preparations employed for the evaluation of acetylcholinesterase inhibition are usually extracted from animal tissues, a procedure suffering from both technical and ethical limitations, which may be alleviated using an in vitro expression system for enzyme generation. For this end, a protocol for stable transfection and selection of zebrafish liver (ZF-L) cells using an adapted expression plasmid "ZF-L Exp" was developed. After insertion of zfAChE cDNA, the enzyme was efficiently expressed in transgenic ZF-L cell lines, which were then used as a high yield source of zfAChE activity for acetylcholinesterase (AChE) inhibition assays.

Assessment of urban stream sediment pollutants entering estuaries using chemical analysis and multiple bioassays to characterise biological activities.

Stormwater contaminants are a major source of often neglected environmental stressors because of the emphasis placed on the management of municipal and industrial wastewaters. Stormwater-derived pollutants in sediments from two New Zealand estuaries was characterised by analytical chemistry and bioassays. Contaminants were extracted from sediment using accelerated solvent extraction (ASE), recovered and concentrated by solid phase extraction (SPE), and analysed for polycyclic aromatic hydrocarbons (PAHs), selected metals, and musk fragrances.

Assessment of cytotoxicity, genotoxicity and 7-ethoxyresorufin-O-deethylase (EROD) induction in sediment extracts from New Zealand urban estuaries.

Sediments represent a major sink for contaminants resulting from industrial and agricultural activities - especially lipophilic substances. This study exclusively used in vitro methodologies to characterize specific toxicity effects of contaminants in sediment extracts from two urban New Zealand estuaries. Sediment extracts were prepared and tested for a range of biological endpoints.

Improving the in vitro ethoxyresorufin-O-deethylase (EROD) assay with RTL-W1 by metabolic normalization and use of β-naphthoflavone as the reference substance.

The ethoxyresorufin-O-deethylase (EROD) assay is a widely applied method for the evaluation of the dioxin-like activity of single substances and environmental samples. As for most enzyme assays, the specific activity is normally related to total protein contents, the determination of which has clear limitations in high-throughput assays. EROD induction potentials are usually expressed as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) equivalents, a substance highly toxic to humans.