Givaudan (Switzerland)

Curcuminoid absorption can be influenced by the presence of additional compounds, but there has been no study investigating this in a robust manner. The aim of this clinical trial was to assess the effect of the type of food matrix on the absorption of curcuminoids from a highly bioavailable turmeric formulation. Participants consumed the turmeric formulation in the form of capsules, a ready-to-drink fruit nectar, a sports nutrition bar, a dairy analogue (oat milk), pectin gummies, and a probiotic drink in a randomized, crossover study. Plasma samples were collected over a 24-hour period to assess the pharmacokinetics of curcuminoids. The relative bioavailability of total curcuminoids was increased in all the food matrices compared to that in the capsule formulation. The dairy analogue showed the highest increase in dose-normalized AUC24 h (+76%, p < 0.0001) and Cmax (+105%, p < 0.0001). The sports nutrition bar resulted in increased dose-normalized AUC24 h (+40%, p = 0.0112) and Cmax (+74%, p < 0.0001). The probiotic drink showed increased dose-normalized AUC24 h (+35%, p = 0.0318) and Cmax (+52%, p < 0.0001). The ready-to-drink and gummy formulations were bioequivalent to the capsules. The distribution of curcuminoid metabolites was similar in all the matrices. In conclusion, there was no negative food matrix effect; on the contrary, the bioavailability of curcuminoids can be improved when administered via food matrices, particularly those containing lipids in a suspended form or polar lipids.

En el contexto colombiano, el Estado se ha transformado en un instrumento que, en algunos casos, incluye la gestión criminal a través de prácticas y dinámicas que han permeado diversos niveles de la sociedad y las instituciones. El presente texto hace una breve introducción en perspectiva histórica para ubicar la dimensión de la situación. Luego, con base en un cúmulo de documentos oficiales y la línea investigativa adelantada por el grupo Kavilando sobre este tema, se presentan características y rutas de la génesis de este orden institucional del mal, de esta reconfiguración del Estado que incluye el orden criminal como parte de su estructura real. Este fenómeno ha instaurado un modelo de administración pública de corte corporativista, que constantemente impide y se opone a la implementación de reformas y ajustes institucionales democráticos necesarios. Estas reformas son cruciales para lograr equidad, justicia, ética en lo público, participación real, verdad y no repetición de violencias pasadas, que son condiciones fundamentales para avanzar hacia una paz participativa, transformadora, sostenible y duradera.

Continuous potency assessment is crucial for conducting quantitative risk assessment (QRA) of sensitizers. Quantitative regression models, based on in vitro methods, have been developed to calculate points of departure for use in skin sensitization QRA. These models calculate a point of departure as a predicted value for Local Lymph Node Assay (LLNA) EC3 or potency value (PV), integrating data from the kinetic Direct Peptide Reactivity Assay (kDPRA), KeratinoSens (KS) assay, and human Cell Line Activation Test (h-CLAT). The goal of this study was to determine how in vitro predicted EC3s and PVs compare to published reference data. In vitro data were combined in point of departure regression models to predict EC3s and PVs. These points of departure were then grouped into sensitization potency categories, such as extreme, strong, moderate, weak, very weak, or non-sensitizer, as previously described. Trends in potency distribution and high concordance between predicted EC3 and PV categories and published potency categories were observed. Furthermore, the median absolute fold-misprediction ranged between 1.8 and 2.5 for models predicting EC3 and between 1.7 and 3.4 for those predicting PVs. These regression models are a promising animal alternative for determining sensitization quantitative potency for fragrance ingredients, thereby facilitating QRA.

The ongoing transition from chemical hazard and risk assessment based on animal studies to assessment relying mostly on non-animal data, requires a multitude of novel experimental methods, and this means that guidance on the validation and standardisation of test methods intended for international applicability and acceptance, needs to be updated. These so-called new approach methodologies (NAMs) must be applicable to the chemical regulatory domain and provide reliable data which are relevant to hazard and risk assessment. Confidence in and use of NAMs will depend on their reliability and relevance, and both are thoroughly assessed by validation. Validation is, however, a time- and resource-demanding process. As updates on validation guidance are conducted, the valuable components must be kept: Reliable data are and will remain fundamental. In 2016, the scientific community was made aware of the general crisis in scientific reproducibility—validated methods must not fall into this. In this commentary, we emphasize the central importance of ring trials in the validation of experimental methods. Ring trials are sometimes considered to be a major hold-up with little value added to the validation. Here, we clarify that ring trials are indispensable to demonstrate the robustness and reproducibility of a new method. Further, that methods do fail in method transfer and ring trials due to different stumbling blocks, but these provide learnings to ensure the robustness of new methods. At the same time, we identify what it would take to perform ring trials more efficiently, and how ring trials fit into the much-needed update to the guidance on the validation of NAMs.

As part of the safety assessment of salicylate esters in cosmetics, we developed a metabolism factor based on in vitro to in vivo extrapolation (IVIVE) to provide a better estimation of the aggregate internal exposure to the common metabolite, salicylic acid. Optimal incubation conditions using human liver S9 were identified before measuring salicylic acid formation from 31 substances. Four control substances, not defined as salicylic esters but which could be mistaken as such due to their nomenclature, did not form salicylic acid. For the remaining substances, higher in vitro intrinsic clearance (CLint, in vitro) values generally correlated with lower LogP values. A “High-Throughput Pharmacokinetic” (HTPK) model was used to extrapolate CLint, in vitro values to human in vivo clearance and half-lives. The latter were used to calculate the percentage of substance metabolised to salicylic acid in 24 h in vivo following human exposure to the ester, i.e. the “metabolism factor”. The IVIVE model correctly reproduced the observed elimination rate of 3 substances using in silico or in vitro input parameters. For other substances, in silico only-based predictions generally resulted in lower metabolism factors than when in vitro values for plasma binding and liver S9 CLint, in vitro were used. Therefore, in vitro data input provides the more conservative metabolism factors compared to those derived using on in silico input. In conclusion, these results indicate that not all substances contribute equally (or at all) to the systemic exposure to salicylic acid. Therefore, we propose a realistic metabolism correction factor by which the potential contribution of salicylate esters to the aggregate consumer exposure to salicylic acid from cosmetic use can be estimated.

O planejamento original do Distrito Federal e sua construção não levaram em consideração a expansão urbana para além do Plano Piloto. Dessa forma, a expansão do uso territorial ocorreu através de processos conhecidos como urbanização dispersa, cujo efeito principal foi a segregação da população vulnerável economicamente da região central. Além disso, o incentivo migratório e a falta de fiscalização fomentaram o surgimento de ocupações informais em todas as partes do Distrito Federal. Além da implicação da proteção ambiental, a permanência da população em ocupações informais está em desacordo com as indicações de moradia adequada. Nesse sentido, os objetivos de desenvolvimento sustentável da Agenda 2030 da Organização das Nações Unidas informam as iniciativas necessárias para tornar as cidades mais justas e sustentáveis.

Dans cet ouvrage qui emprunte son titre une clbre citation de Montaigne voquant l'enrichissement de la langue par les grands crivains, Maria Proshina propose une intressante tude de la prsence des proverbes et expressions idiomatiques dans l'oeuvre de deux des plus grands prosateurs franais du XVI e sicle : Rabelais et Montaigne. 2Brve et allant directement l'essentiel, l'introduction pose la terminologie de l'tude.Une exposition synthtique des dbats linguistiques sur le sujet permet l'tablissement de traits dfinitoires communs aux proverbes et expressions idiomatiques qui, dfaut d'tre incontestables du point de vue thorique, ont du moins le mrite d'tre opratoires dans l'analyse de dtail.L'autrice retient ainsi comme critres l'origine populaire, l'anonymat (par opposition aux maximes, qui expriment la pense d'un individu), l'autonomie grammaticale et smantique, et la mtaphoricit.Les oeuvres de Rabelais et Montaigne offrent cet gard un terrain d'lection, parce qu'elles abondent en tours proverbiaux et idiomatiques, et parce que la crativit exceptionnelle des deux auteurs rend les jeux avec les formules figes particulirement complexes -mme s'il

Introdução: O estilo de vida (EV) é formado por todas as ações e percepções que o indivíduo adota. Os professores e funcionários das universidades tem importante função social dentro das instituições de ensino, contudo durante a pandemia da COVID19 houveram mudanças drásticas na forma de atuar e de viver. Objetivo: Analisar as características de EV de docentes e agentes universitários de uma universidade paranaense e identificar quais fatores mais afetaram o modo de viver dessas pessoas no momento da pandemia. Metodologia: A amostra foi composta por 63 participantes, docentes e funcionários. Todos responderam via plataforma virtual (Google Forms) o questionário EV Fantástico. Quanto mais alta a pontuação melhor, mais seguro e saudável é o EV. Resultados: Foi identificado que os agentes, docentes e terceirizados obtiveram 60%, 37% e 50% respectivamente de EV inadequado. Na dimensão “Atividade Física” dos funcionários observou-se que, quando infectados, a atividade física foi influenciada negativamente, além disso 100% funcionários que tiveram COVID19 estavam com EV inadequado. Quando observada a dimensão “Tipo de Comportamento” do grupo docentes, as docentes apresentaram 83% de casos com perfil menos seguro e saudável. Conclusão: O EV de docentes e funcionários dessa universidade foi caracterizado predominantemente como inseguro e de maior risco à saúde, porém não foi percebida diferença no EV entre pessoas que tiveram COVID19 daquelas que não contraíram, todavia quando funcionários tiveram a infecção, todos os casos se caracterizaram com EV não seguro e saudável. Por fim, as docentes tiveram alta prevalência de estados de ansiedade, pressa e/ou raiva no EV.