Quantitative cross-species extrapolation between humans and fish: The case of the anti-depressant fluoxetine

This article has been made available through the Brunel Open Access Publishing Fund.Fish are an important model for the pharmacological and toxicological characterization of human pharmaceuticals in drug discovery, drug safety assessment and environmental toxicology. However, do fish respond to pharmaceuticals as humans do? To address this question, we provide a novel quantitative cross-species extrapolation approach (qCSE) based on the hypothesis that similar plasma concentrations of pharmaceuticals cause comparable target-mediated effects in both humans and fish at similar level of biological organization (Read-Across Hypothesis). To validate this hypothesis, the behavioural effects of the anti-depressant drug fluoxetine on the fish model fathead minnow (Pimephales promelas) were used as test case. Fish were exposed for 28 days to a range of measured water concentrations of fluoxetine (0.1, 1.0, 8.0, 16, 32, 64 μg/L) to produce plasma concentrations below, equal and above the range of Human Therapeutic Plasma Concentrations (HTPCs). Fluoxetine and its metabolite, norfluoxetine, were quantified in the plasma of individual fish and linked to behavioural anxiety-related endpoints. The minimum drug plasma concentrations that elicited anxiolytic responses in fish were above the upper value of the HTPC range, whereas no effects were observed at plasma concentrations below the HTPCs. In vivo metabolism of fluoxetine in humans and fish was similar, and displayed bi-phasic concentration-dependent kinetics driven by the auto-inhibitory dynamics and saturation of the enzymes that convert fluoxetine into norfluoxetine. The sensitivity of fish to fluoxetine was not so dissimilar from that of patients affected by general anxiety disorders. These results represent the first direct evidence of measured internal dose response effect of a pharmaceutical in fish, hence validating the Read-Across hypothesis applied to fluoxetine. Overall, this study demonstrates that the qCSE approach, anchored to internal drug concentrations, is a powerful tool to guide the assessment of the sensitivity of fish to pharmaceuticals, and strengthens the translational power of the cross-species extrapolation

Effect of mineral-enriched diet and medicinal herbs on Fe, Mn, Zn, and Cu uptake in chicken

<p>Abstract</p> <p>Background</p> <p>The goal of our study was to evaluate the effects of different medicinal herbs rich in polyphenol (Lemon balm, Sage, St. John's wort and Small-flowered Willowherb) used as dietary supplements on bioaccumulation of some essential metals (Fe, Mn, Zn and Cu) in different chicken meats (liver, legs and breast).</p> <p>Results</p> <p>In different type of chicken meats (liver, legs and breast) from chickens fed with diets enriched in minerals and medicinal herbs, beneficial metals (Fe, Mn, Zn and Cu) were analysed by flame atomic absorption spectrometry. Fe is the predominant metal in liver and Zn is the predominant metal in legs and breast chicken meats. The addition of metal salts in the feed influences the accumulations of all metals in the liver, legs and breast chicken meat with specific difference to the type of metal and meat. The greatest influences were observed in legs meat for Fe and Mn. Under the influence of polyphenol-rich medicinal herbs, accumulation of metals in the liver, legs and breast chicken meat presents specific differences for each medicinal herb, to the control group that received a diet supplemented with metal salts only. Great influence on all metal accumulation factors was observed in diet enriched with sage, which had significantly positive effect for all type of chicken meats.</p> <p>Conclusions</p> <p>Under the influence of medicinal herbs rich in different type of polyphenol, accumulation of metals in the liver, legs and breast chicken meat presents significant differences from the group that received a diet supplemented only with metal salts. Each medicinal herb from diet had a specific influence on the accumulation of metals and generally moderate or poor correlations were observed between total phenols and accumulation of metals. This may be due to antagonism between metal ions and presence of other chelating agents (amino acids and protein) from feeding diets which can act as competitor for complexation of metals and influence accumulation of metals in chicken meat.</p> <p><b>Graphical abstract</b></p

Business analytics in industry 4.0: a systematic review

Recently, the term “Industry 4.0” has emerged to characterize several Information Technology and Communication (ICT) adoptions in production processes (e.g., Internet-of-Things, implementation of digital production support information technologies). Business Analytics is often used within the Industry 4.0, thus incorporating its data intelligence (e.g., statistical analysis, predictive modelling, optimization) expert system component. In this paper, we perform a Systematic Literature Review (SLR) on the usage of Business Analytics within the Industry 4.0 concept, covering a selection of 169 papers obtained from six major scientific publication sources from 2010 to March 2020. The selected papers were first classified in three major types, namely, Practical Application, Reviews and Framework Proposal. Then, we analysed with more detail the practical application studies which were further divided into three main categories of the Gartner analytical maturity model, Descriptive Analytics, Predictive Analytics and Prescriptive Analytics. In particular, we characterized the distinct analytics studies in terms of the industry application and data context used, impact (in terms of their Technology Readiness Level) and selected data modelling method. Our SLR analysis provides a mapping of how data-based Industry 4.0 expert systems are currently used, disclosing also research gaps and future research opportunities.The work of P. Cortez was supported by FCT - Fundação para a Ciência e Tecnologia within the R&D Units Project Scope: UIDB/00319/2020. We would like to thank to the three anonymous reviewers for their helpful suggestions

Chemoenzymatic synthesis of narrow-polydispersity glycopolymers: Poly(6-O-vinyladipoly-D-glucopyranose)

The glycomonomer 6-O-vinyladipoyl-D-glucopyranose was prepared via lipase catalyzed transesterification of divinyladipate with alpha-D-glucopyranose in dry acetonitrile and acetone. The desired 6-O regioisomer was obtained in good yield, and its structure was confirmed by correlation NMR spectroscopy. Controlled radical polymerization of the unprotected monomer was performed in protic media using both xanthate and dithiocarbamate as chain transfer agents to give poly(6-O-vinyladipoyl-D-glucopyranose) with M-n of 17 and 19 kDa (SEC) respectively and a polydispersity as low as 1.10. To the best of our knowledge, this is the first example of a narrow-polydispersity, poly(vinyl ester)-like glycopolymer

Safety communication patterns in small work groups - a pilot study using social network analysis

As a project based industry, construction is portrayed through the short term and transitory nature of the industry. This is one of the factors that have been correlated to the poor safety performance of the construction industry. An essential part of safety performance, however, is the effective safety communication between all parties on construction projects. The construction industry is highly regulated due to its high incidence of work-place accidents. This is especially true of smaller building companies/enterprises where the burden of compliance to safety regulations is most onerous. The majority of current research in this topic area has focused on identifying the high risk components or the causes of increased risks. The literature on safety communication network patterns and its relation to safety performance is nevertheless minimal. Thus, this study takes the opportunity to explore the safety communication issue by analyzing the communications patterns in small workgroups. In a pilot study, through surveys with construction crews that are contributing to active construction projects in Sydney, Australia, patterns of safety communications were identified using social network analysis (SNA). The findings, though preliminary, has identified safety communication network patterns under formal communications and toolbox talks may determine a small group&#039;s safety performance

The socio-economic implications of the spatial configuration in greater Cairo metropolitan area

UrbanismArchitecture and The Built Environmen