[Scientific consensus-building to promote the link between science and public policy]. / La recherche de consensus scientifique pour promouvoir le lien entre science et politiques publiques.

Consensus, defined as the position on which most scientists specialized in a given field agree at a given time, is a key aspect in increasing the readability, credibility and, ultimately, the use of scientific knowledge in public (evidence-based health policy). This article presents several methods aiming at developing scientific consensus between experts, such as the conventional or rapid Delphi approach, the nominal group technique, the RAND-UCLA appropriateness method and the consensus development conference. These methods are used to synthesize expert judgements when uncertainties persist in the literature - each with its own specificities in terms of duration, number of steps and expert participants enlisted, as well as the ways in which they are involved.

Le consensus, défini comme la position sur laquelle la plupart des scientifiques spécialistes d'un domaine se mettent d'accord à un moment donné, est un aspect-clé pour augmenter la lisibilité, la crédibilité et in fine l'utilisation des savoirs scientifiques dans les politiques publiques (evidence-based health policy). Cet article présente plusieurs méthodes permettant le développement de consensus entre personnes expertes, telles que l'approche Delphi conventionnelle ou rapide, la technique du groupe nominal, la méthode d'adéquation RAND-UCLA et la conférence de consensus. Ces méthodes permettent la synthèse des jugements experts lorsque des incertitudes persistent dans la littérature ­ chacune avec des spécificités en termes de durée, du nombre d'étapes et de personnes expertes sollicitées, ainsi que des modalités de leur implication.

A harmonized protocol for an international multicenter prospective study of nanotechnology workers: the NanoExplore cohort.

Nanotechnology applications are fast-growing in many industrial fields. Consequently, health effects of engineered nanomaterials (ENMs) should be investigated. Within the EU-Life project NanoExplore, we developed a harmonized protocol of an international multicenter prospective cohort study of workers in ENM-producing companies. This article describes the development of the protocol, sample size calculation, data collection and management procedures and discusses its relevance with respect to research needs. Within this protocol, workers' ENM exposure will be assessed over four consecutive working days during the initial recruitment campaign and the subsequent follow-up campaigns. Biomonitoring using noninvasive sampling of exhaled breath condensate (EBC), exhaled air, and urine will be collected before and after 4-day exposure monitoring. Both exposure and effect biomarkers, will be quantified along with pulmonary function tests and diagnosed diseases reported using a standardized epidemiological questionnaire available in four languages. Until now, this protocol was implemented at seven companies in Switzerland, Spain and Italy. The protocol is well standardized, though sufficiently flexible to include company-specific conditions and occupational hygiene measures. The recruitment, to date, of 140 participants and collection of all data and samples, enabled us launching the first international cohort of nanotechnology workers. All companies dealing with ENMs could join the NanoExplore Consortium, apply this harmonized protocol and enter in the cohort, concieved as an open cohort. Its protocol meets all requirements of a hypotheses-driven prospective study, which will assess and reassess effects of ENM exposure on workers' health by updating the follow-up of the cohort. New hypothesis could be also considered.

[New puff-like disposable electronic cigarettes: expert consensus on their regulation]. / Nouvelles cigarettes électroniques jetables « puffs ¼ : consensus d'expert-e-s sur leur réglementation.

New disposable electronic cigarettes have arrived on the Swiss market since 2020. Our study, conducted according to the three steps of the Delphi fast-track approach developed at Unisanté, obtained a consensual agreement among French-speaking Switzerland experts on the regulation of these products. Ideally, the panel of experts recommends a sales ban of the product. If this is not possible, a number of aspects should be strictly regulated: taxation, product composition and marketing, and sales and consumption restrictions. These regulations should go further than the current European directive and the future Swiss law. The conclusions will be useful to support and guide political decision making from a public health and environmental perspective.

De nouvelles cigarettes électroniques jetables sont arrivées sur le marché suisse depuis 2020. Notre étude, conduite selon les trois étapes de la démarche Delphi fast-track développée à Unisanté, a obtenu un accord consensuel entre expert-e-s suisses romand-e-s sur la réglementation de ces produits. Dans l'idéal, le panel d'expert-e-s recommande une interdiction de vente du produit. Si cela n'est pas possible, certains aspects doivent être strictement réglementés : taxation, composition des produits et marketing, restrictions de vente et de consommation. Ces réglementations devraient aller plus loin que l'actuelle directive européenne et la future loi suisse. Les conclusions seront utiles pour soutenir et orienter la prise de décision politique dans une perspective de santé publique et environnementale.

Urinary Malondialdehyde (MDA) Concentrations in the General Population-A Systematic Literature Review and Meta-Analysis.

Oxidative stress has been associated with various inflammation-related human diseases. It is defined as an imbalance between the production and elimination of reactive oxygen species (ROS). ROS can oxidize proteins, lipids, and DNA, and some of these oxidized products are excreted in urine, such as malondialdehyde (MDA), which is considered a biomarker for oxidative damage of lipids. To interpret changes of this biomarker as a measure of oxidative species overproduction in humans, a background range for urinary MDA concentration in the general population is needed. We sought to establish urinary MDA concentration ranges for healthy adult populations based on reported values in the available scientific literature. We conducted a systematic review and meta-analysis using the standardized protocol registered in PROSPERO (CRD42020146623). EMBASE, PubMed, Web of Science, and Cochrane library databases were searched from journal inception up to October 2020. We included 35 studies (divided into 47 subgroups for the quantitative analysis). Only studies that measured creatinine-corrected urinary MDA with high-performance liquid chromatography (HPLC) with mass spectrometry (MS), fluorescence detection, or UV photometry were included. The geometric mean (GM) of urinary MDA concentration was 0.10 mg/g creatinine and 95% percentile confidence interval (CI) 0.07-0.12. Age, geographical location but not sex, and smoking status had a significant effect on urinary MDA concentrations. There was a significant increasing trend of urinary MDA concentrations with age. These urinary MDA values should be considered preliminary, as they are based on mostly moderate to some low-quality evidence studies. Although urinary MDA can reliably reflect excessive oxidative stress in a population, the influence of physiological parameters that affect its meaning needs to be addressed as well as harmonizing the chemical analytical methods.

Malondialdehyde and anion patterns in exhaled breath condensate among subway workers.

BACKGROUND: Underground transportation systems can contribute to the daily particulates and metal exposures for both commuter and subway workers. The redox and metabolic changes in workers exposed to such metal-rich particles have yet to be characterized. We hypothesize that the distribution of nitrosative/oxidative stress and related metabolic biomarkers in exhaled breath condensate (EBC) are modified depending on exposures. RESULTS: Particulate number and size as well as mass concentration and airborne metal content were measured in three groups of nine subway workers (station agents, locomotive operators and security guards). In parallel, pre- and post-shift EBC was collected daily during two consecutive working weeks. In this biological matrix, malondialdehyde, lactate, acetate, propionate, butyrate, formate, pyruvate, the sum of nitrite and nitrate (ΣNOx) and the ratio nitrite/nitrate as well as metals and nanoparticle concentrations was determined. Weekly evolution of the log-transformed selected biomarkers as well as their association with exposure variables was investigated using linear mixed effects models with the participant ID as random effect. The professional activity had a strong influence on the pattern of anions and malondialdehyde in EBC. The daily number concentration and the lung deposited surface area of ultrafine particles was consistently and mainly associated with nitrogen oxides variations during the work-shift, with an inhibitory effect on the ΣNOx. We observed that the particulate matter (PM) mass was associated with a decreasing level of acetate, lactate and ΣNOx during the work-shift, suggestive of a build-up of these anions during the previous night in response to exposures from the previous day. Lactate was moderately and positively associated with some metals and with the sub-micrometer particle concentration in EBC. CONCLUSIONS: These results are exploratory but suggest that exposure to subway PM could affect concentrations of nitrogen oxides as well as acetate and lactate in EBC of subway workers. The effect is modulated by the particle size and can correspond to the body's cellular responses under oxidative stress to maintain the redox and/or metabolic homeostasis.

Application of the Bayesian spline method to analyze real-time measurements of ultrafine particle concentration in the Parisian subway.

BACKGROUND: Air pollution in subway environments is a growing concern as it often exceeds WHO recommendations for indoor air quality. Ultrafine particles (UFP), for which there is still no regulation nor a standardized exposure monitoring method, are the strongest contributor to this pollution when the number concentration is used as exposure metric. OBJECTIVES: We aimed to assess the real-time UFP number concentration in the personal breathing zone (PBZ) of three types of underground Parisian subway professionals and analyze it using a novel Bayesian spline approach. Consecutively, we investigated the effect of job, week day, subway station, worker location, and some further events on UFP number concentrations. METHODS: The data collection procedure originated from a longitudinal study and lasted for a total duration of 6 weeks (from October 7 to November 15, 2019, i.e. two weeks per type of subway professionals). Time-series were built from the real-time particle number concentration (PNC) measured in the PBZ of professionals during their work-shifts. Complementarily, contextual information expressed as Station, Environment, and Event variables were extracted from activity logbooks completed for every work-shift. A Bayesian spline approach was applied to model the PNC within a Bayesian framework as a function of the mentioned contextual information. RESULTS: Overall, the Bayesian spline method suited a real-time personal PNC data modeling approach. The model enabled estimating the differences in UFP exposure between subway professionals, stations, and various locations. Our results suggest a higher PNC closer to the subway tracks, with the highest PNC on subway station platforms. Studied event and week day variables had a lesser influence. CONCLUSION: It was shown that the Bayesian spline method is suitable to investigate individual exposure to UFP in underground subway settings. This method is informative for better documenting the magnitude and variability of UFP exposure, and for understanding the determinants in view of further regulation and control of this exposure.

Producers of Engineered Nanomaterials-What Motivates Company and Worker Participation in Biomonitoring Programs?

Production and handling of engineered nanomaterials (ENMs) can yield worker exposure to these materials with the potential for unforeseen negative health effects. Biomonitoring enables regular exposure and health assessment and an effective risk management. We aimed to identify factors influencing biomonitoring acceptance according to hierarchical positions of ENM producers. Managers and workers were invited to complete an online questionnaire. Forty-three companies producing or handling ENMs such as titanium dioxide (61%) and multi-walled carbon nanotubes (44%) participated. The majority of managers (72%) and all workers responded positively to participating in biomonitoring studies. The main reasons for refusing participation included concerns about data confidentiality and sufficient knowledge about ENM health and safety. Acquisitions of individual study results, improvement of workers' safety, and help to the development of ENM-specific health and safety practice were among the most valuable reasons for positively considering participation. All workers indicated feeling comfortable with biomonitoring procedures of exhaled air sampling-about half were similarly comfortable with exhaled breath condensate, urine, and buccal cell sampling. The majority of both workers and managers stated that participation in a biomonitoring program should take place during working hours. Although our survey only had limited participation, our results are useful in designing appropriate biomonitoring programs for workers exposed to ENMs.

Effect of nutritive and non-nutritive sweeteners on hemodynamic responses to acute stress: a randomized crossover trial in healthy women.

BACKGROUND: The mechanisms by which chronic stress increases the risk of non-communicable diseases remain poorly understood. On one hand, chronic stress may increase systemic vascular resistance (SVR) and blood pressure, which may lead to blood vessels injury and altered myocardial perfusion. On the other hand, chronic stress may promote the overconsumption of sugar-containing foods and favor obesity. There is indeed evidence that sweet foods are preferentially consumed to alleviate stress responses. The effects of nutritive and non-nutritive sweeteners (NNS) on hemodynamic stress responses remain however largely unknown. OBJECTIVE/DESIGN: This study aimed at comparing the effects of sucrose-containing and NNS-containing drinks, as compared to unsweetened water, on hemodynamic responses to acute stress in twelve healthy female subjects. Acute stress responses were elicited by a 30-min mental stress (5-min Stroop's test alternated with 5-min mental arithmetic) and a 3-min cold pressure test (CPT), each preceded by a resting baseline period. Hemodynamic stress responses were investigated by the repeated measurement of mean arterial pressure and the continuous monitoring of cardiac output by thoracic electrical bioimpedance measurement. SVR was selected as a primary outcome because it is a sensitive measure of hemodynamic responses to acute stress procedures. RESULTS: With all three drinks, SVR were not changed with mental stress (P = 0.437), but were increased with CPT (P = 0.045). Both mental stress and CPT increased mean arterial pressure and heart rate (all P < 0.001). Cardiac output increased with mental stress (P < 0.001) and remained unchanged with CPT (P = 0.252). No significant differences in hemodynamic responses were observed between water, sucrose and NNS (stress × condition, all P > 0.05). CONCLUSIONS: These results demonstrate that sucrose and NNS do not alter hemodynamic responses to two different standardized acute stress protocols.

The extra-splanchnic fructose escape after ingestion of a fructose-glucose drink: An exploratory study in healthy humans using a dual fructose isotope method.

BACKGROUND & AIMS: The presence of specific fructose transporters and fructose metabolizing enzymes has now been demonstrated in the skeletal muscle, brain, heart, adipose tissue and many other tissues. This suggests that fructose may be directly metabolized and play physiological or pathophysiological roles in extra-splanchnic tissues. Yet, the proportion of ingested fructose reaching the systemic circulation is generally not measured. This study aimed to assess the amount of oral fructose escaping first-pass splanchnic extraction after ingestion of a fructose-glucose drink using a dual oral-intravenous fructose isotope method. METHODS: Nine healthy volunteers were studied over 2 h before and 4 h after ingestion of a drink containing 30.4 ± 1.0 g of glucose (mean ± SEM) and 30.4 ± 1.0 g of fructose labelled with 1% [U-13C6]-fructose. A 75%-unlabeled fructose and 25%-[6,6-2H2]-fructose solution was continuously infused (100 µg kg-1 min-1) over the 6 h period. Total systemic, oral and endogenous fructose fluxes were calculated from plasma fructose concentrations and isotopic enrichments. The fraction of fructose escaping first-pass splanchnic extraction was calculated assuming a complete intestinal absorption of the fructose drink. RESULTS: Fasting plasma fructose concentration before tracer infusion was 17.9 ± 0.6 µmol.L-1. Fasting endogenous fructose production detected by tracer dilution analysis was 55.3 ± 3.8 µg kg-1min-1. Over the 4 h post drink ingestion, 4.4 ± 0.2 g of ingested fructose (i.e. 14.5 ± 0.8%) escaped first-pass splanchnic extraction and reached the systemic circulation. Endogenous fructose production significantly increased to a maximum of 165.4 ± 10.7 µg kg-1·min-1 60 min after drink ingestion (p < 0.001). CONCLUSIONS: These data indicate that a non-negligible fraction of fructose is able to escape splanchnic extraction and circulate in the periphery. The metabolic effects of direct fructose metabolism in extra-splanchnic tissues, and their relationship with metabolic diseases, remain to be evaluated. Our results also open new research perspectives regarding the physiological role of endogenous fructose production.

The Impact of Caloric and Non-Caloric Sweeteners on Food Intake and Brain Responses to Food: A Randomized Crossover Controlled Trial in Healthy Humans.

Whether non-nutritive sweetener (NNS) consumption impacts food intake behavior in humans is still unclear. Discrepant sensory and metabolic signals are proposed to mislead brain regulatory centers, in turn promoting maladaptive food choices favoring weight gain. We aimed to assess whether ingestion of sucrose- and NNS-sweetened drinks would differently alter brain responses to food viewing and food intake. Eighteen normal-weight men were studied in a fasted condition and after consumption of a standardized meal accompanied by either a NNS-sweetened (NNS), or a sucrose-sweetened (SUC) drink, or water (WAT). Their brain responses to visual food cues were assessed by means of electroencephalography (EEG) before and 45 min after meal ingestion. Four hours after meal ingestion, spontaneous food intake was monitored during an ad libitum buffet. With WAT, meal intake led to increased neural activity in the dorsal prefrontal cortex and the insula, areas linked to cognitive control and interoception. With SUC, neural activity in the insula increased as well, but decreased in temporal regions linked to food categorization, and remained unchanged in dorsal prefrontal areas. The latter modulations were associated with a significantly lower total energy intake at buffet (mean kcal ± SEM; 791 ± 62) as compared to WAT (942 ± 71) and NNS (917 ± 70). In contrast to WAT and SUC, NNS consumption did not impact activity in the insula, but led to increased neural activity in ventrolateral prefrontal regions linked to the inhibition of reward. Total energy intake at the buffet was not significantly different between WAT and NNS. Our findings highlight the differential impact of caloric and non-caloric sweeteners on subsequent brain responses to visual food cues and energy intake. These variations may reflect an initial stage of adaptation to taste-calorie uncoupling, and could be indicative of longer-term consequences of repeated NNS consumption on food intake behavior.

The impact of replacing sugar- by artificially-sweetened beverages on brain and behavioral responses to food viewing - An exploratory study.

Several studies indicate that the outcome of nutritional and lifestyle interventions can be linked to brain 'signatures' in terms of neural reactivity to food cues. However, 'dieting' is often considered in a rather broad sense, and no study so far investigated modulations in brain responses to food cues occurring over an intervention specifically aiming to reduce sugar intake. We studied neural activity and liking in response to visual food cues in 14 intensive consumers of sugar-sweetened beverages before and after a 3-month replacement period by artificially-sweetened equivalents. Each time, participants were presented with images of solid foods differing in fat content and taste quality while high-density electroencephalography was recorded. Contrary to our hypotheses, there was no significant weight loss over the intervention period and no changes were observed in food liking or in neural activity in regions subserving salience and reward attribution. However, neural activity in response to high-fat, sweet foods was significantly reduced from pre-to post-intervention in prefrontal regions often linked to impulse control. This decrease in activity was associated with weight loss failure, suggesting an impairment in individuals' ability to exert control and adjust their solid food intake over the intervention period. Our findings highlight the need to implement multidisciplinary approaches when aiming to help individuals lose body weight.

Does my brain want what my eyes like? - How food liking and choice influence spatio-temporal brain dynamics of food viewing.

How food valuation and decision-making influence the perception of food is of major interest to better understand food intake behavior and, by extension, body weight management. Our study investigated behavioral responses and spatio-temporal brain dynamics by means of visual evoked potentials (VEPs) in twenty-two normal-weight participants when viewing pairs of food photographs. Participants rated how much they liked each food item (valuation) and subsequently chose between the two alternative food images. Unsurprisingly, strongly liked foods were also chosen most often. Foods were rated faster as strongly liked than as mildly liked or disliked irrespective of whether they were subsequently chosen over an alternative. Moreover, strongly liked foods were subsequently also chosen faster than the less liked alternatives. Response times during valuation and choice were positively correlated, but only when foods were liked; the faster participants rated foods as strongly liked, the faster they were in choosing the food item over an alternative. VEP modulations by the level of liking attributed as well as the subsequent choice were found as early as 135-180ms after food image onset. Analyses of neural source activity patterns over this time interval revealed an interaction between liking and the subsequent choice within the insula, dorsal frontal and superior parietal regions. The neural responses to food viewing were found to be modulated by the attributed level of liking only when foods were chosen, not when they were dismissed for an alternative. Therein, the responses to disliked foods were generally greater than those to foods that were liked more. Moreover, the responses to disliked but chosen foods were greater than responses to disliked foods which were subsequently dismissed for an alternative offer. Our findings show that the spatio-temporal brain dynamics to food viewing are immediately influenced both by how much foods are liked and by choices taken on them. These valuation and choice processes are subserved by brain regions involved in salience and reward attribution as well as in decision-making processes, which are likely to influence prospective dietary choices in everyday life.