A SIMPLE METHOD TO CALIBRATE KINEMATICAL INVARIANTS: APPLICATION TO OVERHEAD THROWING

The aim of this paper is to present a simple calibration method aimed at optimizing the kinematical invariants of a whole body motion capture model, meaning limb lengths and some of the marker placements. A case study and preliminary results are presented and give encouraging insights about the generalized use of such a method in motion analysis in sports

Ability of non-animal methods for skin sensitisation to detect pre- and pro-haptens: Report and recommendations of an EURL ECVAM expert meeting

Significant progress has been made in the development, validation and regulatory acceptance of in chemico and in vitro test methods for skin sensitisation. Although these methods have been shown to perform relatively well (about 80% accuracy in predicting Local Lymph Node Assay (LLNA) classifications) a concern was raised on the regulatory acceptability of negative results since it was questioned whether these methods are able to predict chemicals that need to be activated to act as sensitisers. In order to inform ongoing discussions at the regulatory level in the EU, EURL ECVAM held an expert meeting on 10-11 November 2015 to analyse the extent to which in chemical and in vitro methods are able to correctly identify chemicals that need to be activated either through abiotic activation (pre-haptens) and/or through biotic (enzyme-mediated) mechanisms (pro-haptens) to acquire skin sensitisation potential. The expert group analysed a list of 127 chemicals, with available LLNA and in vitro data, 22% of which were considered to be pre- and/or pro-haptens. The pre-haptens, constituting the vast majority of chemicals requiring activation, where mostly correctly identified by both the in chemico and in vitro assays whereas the pro-haptens which represent a small subset of sensitising chemicals, were generally identified correctly by one of the cell-based assays. As a result, the expert group recommended that negative in vitro data should be accepted unless there is a compelling scientific argument that a substance is likely to be an exclusively metabolically activated pro-hapten.JRC.I.5-Systems Toxicolog

Alternative methods for regulatory toxicology – a state-of-the-art review

This state-of-the art review is based on the final report of a project carried out by the European Commission’s Joint Research Centre (JRC) for the European Chemicals Agency (ECHA). The aim of the project was to review the state of the science of non-standard methods that are available for assessing the toxicological and ecotoxicological properties of chemicals. Non-standard methods refer to alternatives to animal experiments, such as in vitro tests and computational models, as well as animal methods that are not covered by current regulatory guidelines. This report therefore reviews the current scientific status of non-standard methods for a range of human health and ecotoxicological endpoints, and provides a commentary on the mechanistic basis and regulatory applicability of these methods. For completeness, and to provide context, currently accepted (standard) methods are also summarised. In particular, the following human health endpoints are covered: a) skin irritation and corrosion; b) serious eye damage and eye irritation; c) skin sensitisation; d) acute systemic toxicity; e) repeat dose toxicity; f) genotoxicity and mutagenicity; g) carcinogenicity; h) reproductive toxicity (including effects on development and fertility); i) endocrine disruption relevant to human health; and j) toxicokinetics. In relation to ecotoxicological endpoints, the report focuses on non-standard methods for acute and chronic fish toxicity. While specific reference is made to the information needs of REACH, the Biocidal Products Regulation and the Classification, Labelling and Packaging Regulation, this review is also expected to be informative in relation to the possible use of alternative and non-standard methods in other sectors, such as cosmetics and plant protection products.JRC.I.5-Systems Toxicolog

EURL ECVAM Status Report on the Development, Validation and Regulatory Acceptance of Alternative Methods and Approaches (2015)

The EURL ECVAM status report provides an update on the progress made in the development, validation and regulatory acceptance of alternative methods and approaches and their dissemination since the last report published in June 2014. It is informing on ongoing research and development activities, validation studies, peer reviews, recommendations, strategies and regulatory/international acceptance of alternative methods and approaches and dissemination activities. R&D activities within large European or International consortia continued in toxicity areas where 3Rs solutions are more difficult to find due to the underlying complexity of the area. On the other hand, toxicity areas where promising non-animal approaches have been developed, their validation and regulatory acceptance/international adoption could be progressed. Particular emphasis was given to the best and most intelligent combination and integration of these different non-animal approaches to ultimately obtain the required information without resorting to animal testing.JRC.I.5-Systems Toxicolog

A multi-country test of brief reappraisal interventions on emotions during the COVID-19 pandemic.

The COVID-19 pandemic has increased negative emotions and decreased positive emotions globally. Left unchecked, these emotional changes might have a wide array of adverse impacts. To reduce negative emotions and increase positive emotions, we tested the effectiveness of reappraisal, an emotion-regulation strategy that modifies how one thinks about a situation. Participants from 87 countries and regions (n = 21,644) were randomly assigned to one of two brief reappraisal interventions (reconstrual or repurposing) or one of two control conditions (active or passive). Results revealed that both reappraisal interventions (vesus both control conditions) consistently reduced negative emotions and increased positive emotions across different measures. Reconstrual and repurposing interventions had similar effects. Importantly, planned exploratory analyses indicated that reappraisal interventions did not reduce intentions to practice preventive health behaviours. The findings demonstrate the viability of creating scalable, low-cost interventions for use around the world

Genotoxicity and endocrine disruptor effects of food contaminants : hepG2 cell model - molecular mechanisms

L’alimentation peut être à l’origine d’une exposition aux xénobiotiques. Les différentes étapes entre la production et la consommation peuvent être sources de contaminations de cet aliment. L’objectif de ce travail de thèse est de vérifier deux toxicités s’exprimant à faible dose : la génotoxicité et la perturbation endocrinienne. Les xénobiotiques étudiés sont une dioxine (la TCDD, polluant de l’environnement), le glyphosate et ses formulations de Roundup (pesticides), le 5-hydroxyméthylfurfural (molécule néoformée) et le bisphénol F (contaminant d’emballage). Le modèle cellulaire choisi est la lignée cellulaire HepG2, issue d’un hépatocarcinome d’origine humaine. Ces cellules sont un modèle pertinent car elles possèdent des capacités métaboliques bien caractérisées et que les contaminants étudiés sont tous hépatotoxiques. Les résultats ont permis de montrer, avec un test d’activation transcriptionnelle, que les quatre formulations de Roundup étaient antioestrogèniques et antiandrogèniques. Le glyphosate ne présentait que des effets antiandrogèniques. De plus, les formulations modifient l’activité de l’aromatase dans les cellules HepG2. Après quatre heures de contact, le Roundup à 400 g/L présente des effets génotoxiques mais non liés à un stress oxydatif, dans le test des comètes. Il présente également des effets apoptotiques. Les différences observées entre les formulations et les différents éléments de la formulation (le glyphosate et l’adjuvant POEA) suggèrent un « effet mélange ». Le modèle HepG2 a également permis de montrer que le 5-HMF est une molécule progénotoxique à des concentrations non cytotoxiques dans le test des comètes. De plus, il a permis de mettre en évidence le fait que le BPF est la molécule la plus active en matière de génotoxicité et de perturbation endocrinienne, par comparaison avec ses métabolites. Parallèlement, la mise en place d’un modèle stablement transfecté issu des cellules HepG2 a été initiée pour vérifier les potentiels effets (anti)oestrogèniques. Parallèlement, les mécanismes cellulaires et moléculaires à l’origine des effets toxiques observés ont été étudiés. Ainsi, il a été montré que les cellules HepG2 métabolisent le BPF (30% à 25 μM) en sulfoconjugué alors que les hépatocytes humains le métabolisent en sulfoconjugué et/ou glucuroconjugué (100% à 25 μM) avec une différence interindividuelle. Enfin, il a été vérifié, in vitro et dans les conditions expérimentales de l’étude le rôle de ERalpha dans les effets toxiques de la TCDD. Ainsi, un effet anti-oestrogènique de la TCDD sur ERE et un effet potentialisateur de E2 sur l’effet de la TCDD sur XRE ont été mis en évidence. Les tests in vitro ont permis la mise en évidence d’effets toxiques de contaminants de l’alimentation et ont ainsi leur place dans l’évaluation du risque.Food can expose Human to xenobiotics. Indeed, the various steps between production and consumption can be at the origin of food contaminations, either with natural or chemical substances. The objective of this work was to test two toxicities exhibited at low doses: genotoxicity and endocrine disruption. Xenobiotics studied are a dioxin (TCDD, environmental pollutant), glyphosate and different Roundup formulations (pesticides), 5-hydroxymethylfurfural (neoformed compound) and bisphenol F (food packaging contaminant). The model is the HepG2 cell line derived from a human hepatocarcinoma. These cells are chose because they have well-characterized metabolic capacities and all contaminants studied are hepatotoxic. Using transcriptional activation assay, we have shown that the four formulations of Roundup were anti-estrogenic and anti-androgenic. Glyphosate was only anti-androgenic. Furthermore, formulations were able to modify the aromatase activity in HepG2 cells. After 4 hours of contact, the formulation at 400g/L induced genotoxic effect (comet assay) which was not correlated to an oxidative stress or an apoptotic effect (caspase 3,7 activation). The differences observed between the formulation and its components (glyphosate and POEA) suggest a “mixture effect”. We have shown that 5-HMF is a progenotoxic molecule at noncytotoxic concentrations in the comet assay. Also, we have demonstrated that BPF is the most active molecule in genotoxicity and endocrine disruption assays compared to its metabolites. In parallel, the establishment of a stably transfected HepG2 cell line in order to assess the potential (anti)estrogenic effects was initiated.Cellular and molecular mechanisms involved in the toxic effects was also studied. Thus, HepG2 cells metabolized BPF to sulfate metabolite (30% at 25μM), whereas human hepatocytes produced the sulfate and / or glucuronide conjugates (100% at 25μM) with aninterindividual difference. Finally, in vitro and in our experimental conditions, the role of ERin the toxic effects of TCDD was investigated. Using transcriptional activity, TCDD was shown anti-estrogenic on ER. Furthermore, a potention of E2 on transcriptional activity of TCDD induced via AhR was demonstrated. Finally, in vitro assays was used to assess xenobiotic toxicity. They are relevant to in risk assessment

Génotoxicité et potentiel perturbateur endocrinien de contaminants de l'aliment (modèle cellulaire Hep-G2 - mécanismes moléculaires)

L alimentation peut être à l origine d une exposition aux xénobiotiques. Les différentes étapes entre la production et la consommation peuvent être sources de contaminations de cet aliment. L objectif de ce travail de thèse est de vérifier deux toxicités s exprimant à faible dose : la génotoxicité et la perturbation endocrinienne. Les xénobiotiques étudiés sont une dioxine (la TCDD, polluant de l environnement), le glyphosate et ses formulations de Roundup (pesticides), le 5-hydroxyméthylfurfural (molécule néoformée) et le bisphénol F (contaminant d emballage). Le modèle cellulaire choisi est la lignée cellulaire HepG2, issue d un hépatocarcinome d origine humaine. Ces cellules sont un modèle pertinent car elles possèdent des capacités métaboliques bien caractérisées et que les contaminants étudiés sont tous hépatotoxiques. Les résultats ont permis de montrer, avec un test d activation transcriptionnelle, que les quatre formulations de Roundup étaient antioestrogèniques et antiandrogèniques. Le glyphosate ne présentait que des effets antiandrogèniques. De plus, les formulations modifient l activité de l aromatase dans les cellules HepG2. Après quatre heures de contact, le Roundup à 400 g/L présente des effets génotoxiques mais non liés à un stress oxydatif, dans le test des comètes. Il présente également des effets apoptotiques. Les différences observées entre les formulations et les différents éléments de la formulation (le glyphosate et l adjuvant POEA) suggèrent un effet mélange . Le modèle HepG2 a également permis de montrer que le 5-HMF est une molécule progénotoxique à des concentrations non cytotoxiques dans le test des comètes. De plus, il a permis de mettre en évidence le fait que le BPF est la molécule la plus active en matière de génotoxicité et de perturbation endocrinienne, par comparaison avec ses métabolites. Parallèlement, la mise en place d un modèle stablement transfecté issu des cellules HepG2 a été initiée pour vérifier les potentiels effets (anti)oestrogèniques. Parallèlement, les mécanismes cellulaires et moléculaires à l origine des effets toxiques observés ont été étudiés. Ainsi, il a été montré que les cellules HepG2 métabolisent le BPF (30% à 25 M) en sulfoconjugué alors que les hépatocytes humains le métabolisent en sulfoconjugué et/ou glucuroconjugué (100% à 25 M) avec une différence interindividuelle. Enfin, il a été vérifié, in vitro et dans les conditions expérimentales de l étude le rôle de ERalpha dans les effets toxiques de la TCDD. Ainsi, un effet anti-oestrogènique de la TCDD sur ERE et un effet potentialisateur de E2 sur l effet de la TCDD sur XRE ont été mis en évidence. Les tests in vitro ont permis la mise en évidence d effets toxiques de contaminants de l alimentation et ont ainsi leur place dans l évaluation du risque.Food can expose Human to xenobiotics. Indeed, the various steps between production and consumption can be at the origin of food contaminations, either with natural or chemical substances. The objective of this work was to test two toxicities exhibited at low doses: genotoxicity and endocrine disruption. Xenobiotics studied are a dioxin (TCDD, environmental pollutant), glyphosate and different Roundup formulations (pesticides), 5-hydroxymethylfurfural (neoformed compound) and bisphenol F (food packaging contaminant). The model is the HepG2 cell line derived from a human hepatocarcinoma. These cells are chose because they have well-characterized metabolic capacities and all contaminants studied are hepatotoxic. Using transcriptional activation assay, we have shown that the four formulations of Roundup were anti-estrogenic and anti-androgenic. Glyphosate was only anti-androgenic. Furthermore, formulations were able to modify the aromatase activity in HepG2 cells. After 4 hours of contact, the formulation at 400g/L induced genotoxic effect (comet assay) which was not correlated to an oxidative stress or an apoptotic effect (caspase 3,7 activation). The differences observed between the formulation and its components (glyphosate and POEA) suggest a mixture effect . We have shown that 5-HMF is a progenotoxic molecule at noncytotoxic concentrations in the comet assay. Also, we have demonstrated that BPF is the most active molecule in genotoxicity and endocrine disruption assays compared to its metabolites. In parallel, the establishment of a stably transfected HepG2 cell line in order to assess the potential (anti)estrogenic effects was initiated.Cellular and molecular mechanisms involved in the toxic effects was also studied. Thus, HepG2 cells metabolized BPF to sulfate metabolite (30% at 25 M), whereas human hepatocytes produced the sulfate and / or glucuronide conjugates (100% at 25 M) with aninterindividual difference. Finally, in vitro and in our experimental conditions, the role of ER in the toxic effects of TCDD was investigated. Using transcriptional activity, TCDD was shown anti-estrogenic on ER . Furthermore, a potention of E2 on transcriptional activity of TCDD induced via AhR was demonstrated. Finally, in vitro assays was used to assess xenobiotic toxicity. They are relevant to in risk assessment.DIJON-BU Doc.électronique (212319901) / SudocSudocFranceF

A Simple Method to Calibrate Kinematical Invariants: Application to Overhead Throwing

International audienceThe aim of this paper is to present a simple calibration method aimed at optimizing the kinematical invariants of a whole body motion capture model, meaning limb lengths and some of the marker placements. A case study and preliminary results are presented and give encouraging insights about the generalized use of such a method in motion analysis in sports

A Comparative Study of 3 Body Segment Inertial Parameters Scaling Rules

International audienc

Infection maternelle à Parvovirus B19 et anémie fœtale

International audienc