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International audience; The dietary shift from animal protein (AP) to plant protein (PP) sources is encouraged for both environmental and health reasons. For instance, PPs are associated with lower cardiovascular and diabetes risks compared with APs, although the underlying mechanisms mostly remain unknown. Metabolomics is a valuable tool for globally and mechanistically characterizing the impact of AP and PP intake, given its unique ability to provide integrated signatures and specific biomarkers of metabolic effects through a comprehensive snapshot of metabolic status. This scoping review is aimed at gathering and analyzing the available metabolomics data associated with PP- and AP-rich diets, and discusses the metabolic effects underlying these metabolomics signatures and their potential implication for cardiometabolic health. We selected 24 human studies comparing the urine, plasma, or serum metabolomes associated with diets with contrasted AP and PP intakes. Among the 439 metabolites reported in those studies as able to discriminate AP- and PP-rich diets, 46 were considered to provide a robust level of evidence, according to a scoring system, especially amino acids (AAs) and AA-related products. Branched-chain amino acids, aromatic amino acids (AAAs), glutamate, short-chain acylcarnitines, and trimethylamine-N-oxide, which are known to be related to an increased cardiometabolic risk, were associated with AP-rich diets, whereas glycine (rather related to a reduced risk) was associated with PP-rich diets. Tricarboxylic acid (TCA) cycle intermediates and products from gut microbiota AAA degradation were also often reported, but the direction of their associations differed across studies. Overall, AP- and PP-rich diets result in different metabolomics signatures, with several metabolites being plausible candidates to explain some of their differential associations with cardiometabolic risk. Additional studies specifically focusing on protein type, with rigorous intake control, are needed to better characterize the associated metabolic phenotypes and understand how they could mediate differential AP and PP effects on cardiometabolic risk.

Background Plant-based substitutes are designed to have the same use as animal-based foods in the diet and could therefore assist the transition toward more plant-based diets. However, their nutritional impact has not been characterized. Objectives We assessed and compared the effects of plant-based substitutes on the nutritional quality of the diet. Methods We simulated separately the substitution of meat, milk, and dairy desserts with 96 plant-based substitutes in the diets of 2121 adults (18-79 y old) from the cross-sectional French Third Individual and National Study on Food Consumption Survey (INCA3; 2014-2015). The quality of initial individual diets and the 203,616 substituted diets was evaluated using the Probability of Adequate Nutrient Intake (PANDiet) scoring system, which assesses the probability of adequate (sufficient and not excessive) nutrient intake; also, nutrient security was evaluated using the SecDiet scoring system, which assesses the risk of overt deficiency. Results Impacts on PANDiet depended on both the food substituted and the types of substitutes. Soy-based substitutes provided a slight improvement in diet quality (0.8% increase of the PANDiet score when substituting meat), whereas cereal-based substitutes resulted in a 1.1% decrease. Globally, substitutions led to better adequacies for fiber, linoleic acid, α-linolenic acid, vitamin E, folate, and SFAs, but lower adequacies regarding vitamin B-12 and riboflavin, as well as bioavailable zinc and iron when substituting meat, and calcium and iodine when substituting milk/dairy desserts. When they substituted dairy products, calcium-fortified substitutes allowed maintenance of calcium adequacy but there was a higher risk of iodine deficiency when substituting dairy, which may warrant iodine fortification. Substitutions modified the energy share of ultra-processed foods from 29% to 27%-40%, depending on the food substituted and the substitute used. Conclusions Plant-based substitutes had a small effect on overall diet quality and heterogeneous impacts on nutrient adequacy and security. Plant-based substitutes that include legumes appear more nutritionally adequate to substitute animal products than do other substitutes.

Although micronutrient deficiencies affect 2 billion people worldwide, no index focuses on measuring the risk of overt nutrient deficiency. We aimed to develop an index that could capture the nutrient dimension of nutritional security, a nutrient security index (named SecDiet), and evaluate its apparent validity. The SecDiet (range: 0–1) is based on the square-weighted average of the probabilities that the intake of twelve critical nutrients exceeds the threshold value associated with a risk of overt deficiency. Using adult populations from a French representative survey (INCA3, n 1774) and a large cohort (NutriNet-Santé, n 104 382), the content and construct validity of the SecDiet was evaluated by estimating associations of the SecDiet with its components and with relevant socio-demographic characteristics. The SecDiet was high in the overall population (0·93 (SD 0·09) in INCA3) and markedly skewed towards 1 (i.e. lower risk of insufficient intake). It correlated positively with its twelve components (r 0·17–0·78, all P < 0·001). The SecDiet was associated with monthly income (P = 0·002), perception of financial situation, professional situation, food insufficiency and security statuses (all P < 0·001) in the INCA3 population and with monthly income, professional situation and level of education (all P < 0·001) in the NutriNet-Santé population. Unlike a broader nutrient-based quality index taken as comparison, the SecDiet mean decreased and the tail of its distribution notably extended downwards in at-risk sub-populations, thus revealing its specific sensitivity. The SecDiet could be used to screen sub-groups or study the determinants of nutrient insecurity in large population surveys.

Transport of infected birds is thought to play a key role in the spread of avian influenza (AI) on poultry farms during epizootic outbreaks. Ensuring efficient cleaning and disinfection (C&D) of equipment used for transport is needed to prevent the spread of AI. This study aimed to evaluate the efficacy against the AI virus of C&D protocols applied on trucks and crates used for the transport of ducks during the H5N8 AI outbreaks in France in 2017. In 3 abattoirs, 16 transport vehicles and their crates were sampled by swabbing to detect the influenza type A genome by real-time reverse-transcription polymerase chain reaction. Vehicles were tested before and after decontamination, which was carried out in accordance with the abattoirs' protocols. A total of 86 samples out of 299 collected before C&D were positive for AI (29%); 7 trucks out of 16 transported crates detected positive for AI. After C&D, the AI genome was detected in 56 samples out of 308 (18%). Ten trucks were loaded with a shipment of AI-positive crates. Eight vehicles were detected positive in the cabin, on the truck bed, and/or on the wheels. Despite reinforcement of C&D, the efficacy of decontamination was variable among slaughterhouses. The efficacy seemed to depend on the initial contamination load, C&D protocols, and how the protocol is implemented. Breaks in biosecurity measures led to frequent contamination of trucks after C&D. Observational studies during animal health crises are of interest to analyze practices in emergency conditions and to put forward measures aimed at increased preparedness.

International audience; Tailored dietary counseling could be specifically efficient during pregnancy, a period accompanied by a rise in nutrition awareness, but little is known about the expectations of pregnant women in this regard. We studied these expectations regarding tailored dietary advice in French women during their pregnancy, as well as their motivations and the perceived barriers and enablers. In French pregnant women, we evaluated the perceptions of tailored dietary advice provided by stepwise dietary counseling based on three types of dietary changes, consisting of: (1) a modification of the amounts consumed, (2) substitutions within the food subgroups, and (3) substitutions between food subgroups. A sequential explanatory mixed-method approach was designed. Using qualitative data from a focus group study (n = 40), we intended to explore in depth the women’s expectations regarding dietary advice and adherence to a tailored approach. These were combined with quantitative and qualitative data from a 6-week online longitudinal study (n = 115), using questionnaires designed to assess the modifications of dietary habits during pregnancy and to evaluate each type of dietary change. Both studies confirmed that most women in our samples did indeed intend to institute changes regarding healthier dietary practices during pregnancy. The principal motivation behind changes to their habits was to ensure the health and well-being of both their babies and themselves. The proposal of dietary advice that is tailored to both the current diet and the specific needs of pregnant women, but that is also positive and credible, was perceived as enabling implementing healthier dietary practices during pregnancy. Regarding the implementation of the dietary changes proposed, the enablers and barriers identified differed between modifications of the amounts consumed and substitutions. The women displayed interest in all types of dietary changes. This gave relevance to combining different types of changes in order to propose dietary counseling during pregnancy. Tailored dietary counseling was identified by French pregnant women in our samples as enabling them to adopt a healthier diet. However, perceived barriers might limit the implementation of dietary changes, especially when they involved marked modifications to their usual diet.

[EN] Rabbit haemorrhagic disease (RHD) is a critical health threat to the rabbit industry in Europe. In 2018, the French rabbit industry adopted a voluntary control plan against this disease. In this context, two epidemiological studies were conducted on RHD outbreaks that occurred between 2013 and 2018 in France. The objectives were to describe the spread of RHD due to the new genotype RHDV GI.2 (rabbit haemorrhagic disease virus GI.2) and to identify rearing factors influencing the occurrence of the disease in order to guide the prevention measures recommended in the control plan. An analysis of cases on 295 farms between 2013 and 2017 showed that 32% of farms were affected at least once; the incidence of the disease increased in 2016-2017 compared to 2013-2015. Farms already affected in 2013-2015 had a higher risk of being infected in 2016-2017 than those that remained unaffected until 2015 (Relative Risk and 95% Confident Interval 1.7 [1.1-2.7]). A case-control study carried out between 2016 and 2018 on 37 outbreaks and 32 control farms revealed variability in biosecurity and decontamination practices between farms. The risk of being infected tends to be linked to these practices, but certain structural factors (e.g. the manure disposal system, transfer of rabbits at weaning) could also influence the risk of virus introduction into farms. In the context of a limited vaccination coverage of the farms (only females are vaccinated), these hypotheses will be studied further, using information from the RHD outbreak monitoring system implemented at the same time as the control plan in 2018., This study was founded by the French Ministry of Agriculture (2017-430 / 170274).

Among crop fruit trees, the apricot (Prunus armeniaca) provides an excellent model to study divergence and adaptation processes. Here, we obtain nearly 600 Armeniaca apricot genomes and four high-quality assemblies anchored on genetic maps. Chinese and European apricots form two differentiated gene pools with high genetic diversity, resulting from independent domestication events from distinct wild Central Asian populations, and with subsequent gene flow. A relatively low proportion of the genome is affected by selection. Different genomic regions show footprints of selection in European and Chinese cultivated apricots, despite convergent phenotypic traits, with predicted functions in both groups involved in the perennial life cycle, fruit quality and disease resistance. Selection footprints appear more abundant in European apricots, with a hotspot on chromosome 4, while admixture is more pervasive in Chinese cultivated apricots. Our study provides clues to the biology of selected traits and targets for fruit tree research and breeding., The evolutionary and domestication history of apricots is poorly understood. Here, the authors provide four apricot high-quality genome assemblies, the genomes of 578 accessions from natural and cultivated populations, and show that Chinese and European apricots constitute two different gene pools, resulting from independent domestication events.

International audience; Abstract Objectives While consumers’ demand is growing, meat substitutes have much varied composition, raising questions about their nutritional interest. We aimed to identify the composition of a meat substitute that would best improve diet quality, and analyze the impact on nutrient adequacy. Methods We aimed at maximizing the overall diet quality of an average individual representing the nutrient intake of the French adult population (INCA3, n = 1125) by modeling the composition of a meat substitute intended to replace meat, using non-linear optimization (using SAS, proc optmodel). The diet quality was assessed using the PANDiet scoring system, which assesses the probability of adequate nutrient intake. Nutritional constraints were applied in order to not increase the risk of overt deficiency for 12 nutrients. A list of 159 ingredients was used to compose the meat replacer and technological constraints were defined so as to take into account the feasibility of the formulation. The impacts on diet quality of the modelled meat substitute were analyzed and compared with those of 43 meat substitutes on the market. Results The optimized meat substitute was composed of 13 ingredients (such as coco bean, yellow sweet pepper, rapeseed oil, dried shiitake mushroom, wheat bran and thyme) and this formulation proved to be relatively robust to variations in the model constraints, as shown by a sensitivity analysis. Meat substitution with this optimized meat substitute largely increased the PANDiet, by 5.5 points above its initial value before substitution (73.7/100). In particular, it led to better adequacies for nutrients that are currently insufficiently consumed (e.g., alpha-linolenic acid, fiber, linoleic acid). It also allowed to compensate for loss of some nutrients partly provided by meat (e.g., vitamin B6, potassium and, to a certain extent, bioavailable iron), but was not sufficient to compensate for bioavailable zinc and vitamin B12. The optimized meat substitute proved to be dramatically more nutritionally efficient than the available meat substitutes, whose individual impact on the PANDiet ranged from −3.1 to +1.5 points. Conclusions We proved that it is possible to select appropriate ingredients resulting in a meat substitute that could be a fairly good nutritional lever when substituting meat. Funding Sources Partly funded by a PhD fellowship from Terres Univia.

International audience; Objectives We aimed to study if, and to what extent, the current nutrient reference values for bioavailable iron and zinc limit the identification of healthier dietary patterns. Methods Using observed diets from a representative French survey (INCA3) and multi-criteria optimization, we identified diets that comply with all nutrient reference values and maximize a health criteria based on food-based dietary guidelines while minimally departing from the observed diet. Nutrient reference values included absorbed iron and zinc. This non-linear diet optimization problem was solved in men and women with higher (Fe−) and lower (Fe+) iron requirements separately, either strictly (Non Flexible model, NF) or by allowing some tolerance on absorbed iron and zinc using goal programming to minimize their decreases below reference values (Flexible Model, F). Using a comparative risk assessment framework and a probabilistic approach, we estimated changes in risks of cardiovascular diseases, diabetes and colorectal cancer, and changes in estimates of the prevalence of iron-deficiency anemia for the diets optimized using each model. Results With the NF model, the reference values for absorbed iron and zinc were the most binding constraints (over 34 constraints). Compared to the observed diets, the NF-optimized diets showed large redistributions within cereals and meats, with total meat consumption remaining similar in men and Fe- women and doubling in Fe + women. In contrast, the F-optimized diets had higher value for the health criteria objective, being systematically lower in meat, especially red meat, and higher in whole grain products. We estimated that the reduction in mortality risk would be 17.7% wih the NF-optimized diets and 21.5% with the F-optimized diets. However, the later diets would increase the prevalence of iron-deficiency anemia from 2.1% currently to 5.6%. Conclusions We evidenced that the reference values for iron and zinc with regard to their bioavailability are critical factors when modelling healthy eating patterns. Considering lower references for iron and zinc leads to identify diets with an apparent higher benefit for the population health with regards long-term health. Funding Sources None.

BACKGROUND AND OBJECTIVES: Use of mid–upper arm circumference (MUAC) as a single screening tool for severe acute malnutrition (SAM) assumes that children with a low weight-for-height z score (WHZ) and normal MUAC have lower risks of morbidity and mortality. However, the pathophysiology and functional severity associated with different anthropometric phenotypes of SAM have never been well characterized. We compared clinical characteristics, biochemical features, and health and nutrition histories of nonedematous children with SAM who had (1) low WHZ only, (2) both low WHZ and low MUAC, or (3) low MUAC only. METHODS: In Bangladesh, Burkina Faso, and Liberia, we conducted a multicentric cohort study in uncomplicated, nonedematous children with SAM and low MUAC only (n = 161), low WHZ only (n = 138), or a combination of low MUAC and low WHZ (n = 152). Alongside routine anthropometric measurements, we collected a wide range of critical indicators of clinical and nutritional status and viability; these included serum leptin, an adipocytokine negatively associated with mortality risk in SAM. RESULTS: Median leptin levels at diagnosis were lower in children with low WHZ only (215.8 pg/mL; P < .001) and in those with combined WHZ and MUAC deficits (180.1 pg/mL; P < .001) than in children with low MUAC only (331.50 pg/mL). The same pattern emerged on a wide range of clinical indicators, including signs of severe wasting, dehydration, serum ferritin levels, and caretaker-reported health deterioration, and was replicated across study sites. CONCLUSIONS: Illustrative of the likely heterogeneous functional severity of the different anthropometric phenotypes of SAM, our results confirm the need to retain low WHZ as an independent diagnostic criterion.

International audience; Purpose. While the consumption of ultra-processed foods is steadily increasing, there is a growing interest in more sustainable diets that would include more plant protein. We aimed to study associations between the degree of food processing, patterns of protein intake, diet quality and cardiometabolic risk.Methods. Using the NOVA classification, we assessed the proportion of energy from unprocessed/minimally processed foods (MPFp), processed foods (PFp) and ultra-processed foods (UPFp) in the diets of 1774 adults (18-79y) from the latest cross-sectional French national survey (INCA3, 2014-2015). We studied the associations between MPFp, PFp and UPFp with protein intakes, diet quality (using the PANDiet scoring system, the global (PDI), healthful (hPDI) and unhealthful (uPDI) plant-based diet indices) and the risk of cardiometabolic death (using the EpiDiet model). Results. MPFp was positively associated with animal protein intake and plant-protein diversity, whereas PFp was positively associated with plant protein intake and negatively with plant-protein diversity. The PANDiet was positively associated with MPFp (β=0.14, P

Improving the sustainability of diets requires the identification of diets that meet the nutritional requirements of populations, promote health, are within planetary boundaries, are affordable and are acceptable. Here we explore the extent to which dimensions of sustainability could be optimally aligned and identify more sustainable dietary solutions, from the most conservative to the most disruptive, among 12,166 participants of the NutriNet-Sante cohort. We aim to concomitantly lower environmental impacts (including greenhouse gas emissions, cumulative energy demand and land occupation), increase organic food consumption and study departure from observed diets (considered as a proxy for acceptability). From the most conservative to the most disruptive scenario, optimized diets were gradually richer in fruits, vegetables and soya-based products and markedly poorer in animal-based foods and fatty and sweet foods. The contribution of animal protein to total protein intake gradually decreased by 12% to 70% of the observed value. The greenhouse gas emissions from food production for the diets gradually decreased across scenarios (as a percentage of observed values) by 36–86%, land occupation for food production by 32–78% and energy demand by 28–72%. Our results offer a benchmark of scenarios of graded dietary changes against graded sustainability improvements. Conservative to disruptive changes in dietary patterns of French adults from the NutriNet-Sante cohort are considered for reducing environmental impacts, increasing organic food consumption, providing adequate nutrition and being economically acceptable. A progressive substitution of animal products by plant products across dietary scenarios more closely aligned dimensions of sustainability.

International audience; The EAT-Lancet Commission has recently proposed a “universal” healthy reference diet. However, no study has specifically investigated its possible environmental benefits at the individual level based on observed data. Our objective was therefore to characterize the environmental pressures and impacts related to the level of adherence to the EAT-Lancet diet among French adults. Dietary data from a 264-item FFQ in 29,210 NutriNet-Santé participants (75% women, mean age = 53.5y (SD = 14.0)), were used to estimate (i) the level of adherence to the EAT-Lancet diet through the EAT-Lancet diet index (ELD-I), (ii) the food production-related environmental impacts using 3 individual environmental indicators (greenhouse gas emissions, cumulative energy demand and land occupation) and (iii) the overall environmental impact using a validated aggregated partial score (pReCiPe). For clarity purpose, results are presented by quintile (Q) of ELD-I. High ELD-I (Q5), compared to low (Q1), was associated with lower greenhouse gas emissions (−56%), cumulative energy demand (−31%) and land occupation, (−54%). The pRECIPE was 62% lower in high ELD-I than in low ELD-I but the range of pReCiPe in Q1 was large. In this large scale-study of French adults, adherence to the EAT-Lancet recommendations led to lower environmental impacts. Nonetheless, some low-EAT diets (reflecting unhealthy diets), may exhibit low environmental impacts.

International audience; Background: Healthier dietary patterns involve more plant-based foods than current Western diets rich in animal products containing high levels of bioavailable iron and zinc. Little consideration is given to the bioavailability of iron and zinc when studying healthy eating patterns.Objectives Our aim was to determine whether currently estimated requirements for bioavailable iron and zinc limit the identification of healthier dietary patterns.Methods Using dietary data from a representative French survey and multi-criteria non-linear optimization, we identified diets that maximize health criteria based on Food-Based Dietary Guidelines and concomitantly depart only minimally from the observed diet, while complying with all nutrient reference values either strictly (non-flexible optimization) or by allowing bioavailable iron and zinc below the current reference values, but to a limited extent (flexible optimization). Using a comparative risk assessment model, we estimated the resulting impact on cardiometabolic and colorectal cancer mortality/morbidity, and changes to iron-deficiency anemia.Results Under non-flexible optimization, reference values for bioavailable iron and zinc were the most binding of the 35 nutrient constraints and modeled diets displayed considerable redistributions within grains and meat. With flexible optimization, modeled diets were healthier as they contained less red meat and more whole-grain products, but would increase iron-deficiency anemia to 5.0% (95% CI: 3.9%, 6.4%). Globally, in terms of Disability Adjusted Life Years (DALYs), as the loss due to anemia would represent

White lupin (Lupinus albus L.) is an annual crop cultivated for its protein-rich seeds. It is adapted to poor soils due to the production of cluster roots, which are made of dozens of determinate lateral roots that drastically improve soil exploration and nutrient acquisition (mostly phosphate). Using long-read sequencing technologies, we provide a high-quality genome sequence of a cultivated accession of white lupin (2n = 50, 451 Mb), as well as de novo assemblies of a landrace and a wild relative. We describe a modern accession displaying increased soil exploration capacity through early establishment of lateral and cluster roots. We also show how seed quality may have been impacted by domestication in term of protein profiles and alkaloid content. The availability of a high-quality genome assembly together with companion genomic and transcriptomic resources will enable the development of modern breeding strategies to increase and stabilize white lupin yield., White lupin is an annual crop cultivated for protein rich seeds and can produce cluster roots for efficient phosphate acquisition. Here, the authors generate high quality genome assemblies of a cultivated accession, a landrace, and a wild relative and provides insight into soil exploration and seed quality.

Natural abundances of stable nitrogen and carbon isotopes (δ15N and δ13C) can vary with both dietary intake and metabolic (specifically catabolic) state. In low-income countries, weaning is a period of dietary transition from milk to plant-based foods and a high-risk period for malnutrition. We explored how diet and malnutrition impact hair δ15N and δ13C in young children by an observational, cross-sectional study in Cox’s Bazar District, Bangladesh [255 children, 6–59 months with 19.6% wasted (7.1% severely) and 36% stunted (9.8% severely)]. Hair δ15N and δ13C exhibited exponential decreases with age, with the loss of one trophic level (3.3‰ and 0.8‰, respectively) from 6 to 48 months, which we associate with the shift from exclusive breastfeeding to complete weaning. After adjustment for age and breastfeeding status, hair isotopic values were unaffected by wasting but lower in severe stunting (−0.45‰ to −0.6‰, P 15N and δ13C values in severely stunted children that likely indicate chronic exposure to diets low in animal products.

Little is known about the effects of the development of metabolic syndrome (MS) on protein and amino acid (AA) metabolism. During this study, we took advantage of the variability in interindividual susceptibility to high fat diet-induced MS to study the relationships between MS, protein synthesis, and AA catabolism in multiple tissues in rats. After 4 mo of high-fat feeding, an MS score (ZMS) was calculated as the average of the z-scores for individual MS components [weight, adiposities, homeostasis model for the assessment of insulin resistance (HOMA-IR), and triglycerides]. In the small intestine, liver, plasma, kidneys, heart, and muscles, tissue protein synthesis was measured by 2H2O labeling, and we evaluated the proportion of tissue AA catabolism (relative to protein synthesis) and nutrient routing to nonindispensable AAs in tissue proteins using natural nitrogen and carbon isotopic distances between tissue proteins and nutrients (Δ15N and Δ13C), respectively. In the liver, protein mass and synthesis increased, whereas the proportion of AA catabolism decreased with ZMS. By contrast, in muscles, we found no association between ZMS and protein mass, protein synthesis (except for a weak positive association in the gastrocnemius muscle only), and proportion of AA catabolism. The development of MS was also associated with altered metabolic flexibility and fatty acid oxidation, as shown by less routing of dietary lipids to nonindispensable AA synthesis in liver and muscle. In conclusion, MS development is associated with a greater gain of both fat and protein masses, with higher protein anabolism that mainly occurs in the liver, whereas muscles probably develop anabolic resistance due to insulin resistance.

Background and Objective Neurovascular coupling is the complex biological process that underlies use‐dependent increases in blood flow in response to neural activation. Neurovascular coupling was investigated at the early stage of CADASIL, a genetic paradigm of ischemic small vessel disease. Methods Functional hyperemia and evoked potentials during 20‐ and 40‐sec visual and motor stimulations were monitored simultaneously using arterial spin labeling‐functional magnetic resonance imaging (ASL‐fMRI) and electroencephalography. Results Cortical functional hyperemia differed significantly between 19 patients and 19 healthy individuals, whereas evoked potentials were unaltered. Functional hyperemia dynamics, assessed using the difference in the slope of the response curve between 15 and 30 sec, showed a time‐shifted decrease in the response to 40‐sec neural stimulations in CADASIL patients. These results were replicated in a second cohort of 10 patients and 10 controls and confirmed in the whole population. Interpretation Alterations of neurovascular coupling occur early in CADASIL and can be assessed by ASL‐fMRI using a simple marker of vascular dysfunction.

Summary Cucumis melo displays a large diversity of horticultural groups with cantaloupe melon the most cultivated type. Using a combination of single-molecule sequencing, 10X Genomics link-reads, high-density optical and genetic maps, and chromosome conformation capture (Hi-C), we assembled a chromosome scale C. melo var. cantalupensis Charentais mono genome. Integration of RNA-seq, MeDip-seq, ChIP-seq, and Hi-C data revealed a widespread compartmentalization of the melon genome, segregating constitutive heterochromatin and euchromatin. Genome-wide comparative and evolutionary analysis between melon botanical groups identified Charentais mono genome increasingly more divergent from Harukei-3 (reticulatus), Payzawat (inodorus), and HS (ssp. agrestis) genomes. To assess the paleohistory of the Cucurbitaceae, we reconstructed the ancestral Cucurbitaceae karyotype and compared it to sequenced cucurbit genomes. In contrast to other species that experienced massive chromosome shuffling, melon has retained the ancestral genome structure. We provide comprehensive genomic resources and new insights in the diversity of melon horticultural groups and evolution of cucurbits., Graphical abstract, Highlights • We provide a chromosome scale C. melo var. cantalupensis Charentais mono genome • Epigenomic analysis revealed a widespread compartmentalization of the melon genome • We reconstructed the ancestral Cucurbitaceae karyotype • Melon has retained the ancestral Cucurbitaceae genome structure, Genomics; Omics; Plant biology; Plant evolution

A growing body of evidence supports a role for tissue-to-diet 15N and 13C discrimination factors (&Delta, 15N and &Delta, 13C), as biomarkers of metabolic adaptations to nutritional stress, but the underlying mechanisms remain poorly understood. In obese rats fed ad libitum or subjected to gradual caloric restriction (CR), under a maintained protein intake, we measured &Delta, 13C levels in tissue proteins and their constitutive amino acids (AA) and the expression of enzymes involved in the AA metabolism. CR was found to lower protein mass in the intestine, liver, heart and, to a lesser extent, some skeletal muscles. This was accompanied by &Delta, 15N increases in urine and the protein of the liver and plasma, but &Delta, 15N decreases in the proteins of the heart and the skeletal muscles, alongside &Delta, 13C decreases in all tissue proteins. In Lys, &Delta, 15N levels rose in the plasma, intestine, and some muscles, but fell in the heart, while in Ala, and to a lesser extent Glx and Asx, &Delta, 13C levels fell in all these tissues. In the liver, CR was associated with an increase in the expression of genes involved in AA oxidation. During CR, the parallel rises of &Delta, 15N in urine, liver, and plasma proteins reflected an increased AA catabolism occurring at the level of the liver metabolic branch point, while &Delta, 15N decreases in cardiac and skeletal muscle proteins indicated increased protein and AA catabolism in these tissues. Thus, an increased protein and AA catabolism results in opposite &Delta, 15N effects in splanchnic and muscular tissues. In addition, the &Delta, 13C decrease in all tissue proteins, reflects a reduction in carbohydrate (CHO) oxidation and routing towards non-indispensable AA, to achieve fuel economy.

Few studies have previously investigated how poor animal welfare might be associated with infection of zoonotic pathogens in humans. This paper assesses the predictive value of the presence of Campylobacter spp. in broiler chicken flocks when animal-based measures related to footpad dermatitis, hock burns, body lesions and arthritis are identified under commercial conditions (high density). The study population included 32 flocks analysed on farm and at slaughter, slaughtered between April and August 2008 in six different slaughter plants in Brittany, France. Welfare and health indicators are those indicated by the European legislation and sampling was carried out in the framework of the European baseline survey on the prevalence of Campylobacter in broiler chicken. Caecal contents, sampled both on farm and at slaughter, and carcass skin samples from the neck and breast at slaughter, were investigated for the presence of Campylobacter spp. Logistic models/classification trees were used to estimate the probability of the presence (or absence) of a specific foodborne pathogen in a flock based on specific animal-based measures (or combinations of measures) in order to study the potential relationship between welfare indicators and foodborne pathogen prevalence/incidence levels. On farm, flocks with more than 25% animals with severe lesions on between 25 and 50% of the footpad are predicted to be Campylobacter-positive whereas flocks where less than 13 individuals have arthritis are predicted to be Campylobacter-negative. The error rate on farm and at slaughter was 10 and 4% respectively indicating good predicting abilities. A poor welfare environment may result in stress, which reduces chicken immunocompetence making them more susceptible to Campylobacter spp. An infection with Campylobacter spp may lead to impaired defence and susceptibility to other pathogens which may result in greater intestinal excretion. Poor welfare and high growing rate lead to digestive troubles that lead to litter humidity. Litter humidity that, among other things, causes footpad dermatitis may also influence the horizontal transmission of the Campylobacter spp. infection due to the normal coprophagic behaviour of poultry. Reducing welfare problems by a better management of rearing conditions would not only improve broiler welfare, but it would also decrease the risks of Campylobacter contamination, of carcass condemnations and of economic loss for the poultry industry.

International audience; Background: Toll-like receptor 4 (TLR4), an innate immune receptor, is suspected to play a key role in the postprandial inflammation that is induced by a high-fat meal rich in saturated fatty acids (SFA). Our objective was to test this hypothesis by using a specific competitive inhibitor of TLR4 (INH) vs vehicle (VEH) administered immediately before a high-SFA meal in rats.Methods: First, in a cross-over kinetic study of 12 rats receiving INH and VEH i.v. 10 min before the test meal, we measured plasma inflammatory and vascular markers for 6 h. Then, in 20 rats, 3 h after INH or VEH followed by the test meal (parallel study), we measured the mRNA level of a set of cytokines (Il1-β, Il-6, Tnfα, Mcp-1, Pai-1), and of Tlr4 and Tlr2 in the adipose tissue and the liver, and that of adhesion molecules (Icam-1 and Vcam-1) in the aorta.Results: Plasma IL-6 and PAI-1 increased >4-fold at 3–4 h after test-meals, very similarly after INH as compared to VEH. The expression of TLR2 and of all measured cytokine genes in the adipose tissue was dramatically higher after INH (vs VEH). In the liver, gene expression of Il1-β, Tnfα, Mcp-1 and Tlr2, was also higher after INH, though more moderately, whereas that of Il-6 and Pai-1 was similar between groups. INH did not affect mRNA level of Icam-1 and Vcam-1 in the aorta.Conclusion: TLR4 activation is not specifically required to mediate systemic postprandial inflammation and we propose that TLR2 and TLR4 exert a dual and interdependent mediation of the postprandial inflammatory response, at least in the adipose tissue.

Background and aims - Pharmacologically controlled drinking in the treatment of alcohol dependence or alcohol use disorders (AUDs) is an emerging concept. Our objective was to explore the comparative effectiveness of drugs used in this indication. Design - Systematic review with direct and network meta-analysis of double-blind randomized controlled trials (RCTs) assessing the efficacy of nalmefene, naltrexone, acamprosate, baclofen or topiramate in non-abstinent adults diagnosed with alcohol dependence or AUDs. Two independent reviewers selected published and unpublished studies on Medline, the Cochrane Library, Embase, ClinicalTrials.gov, contacted pharmaceutical companies, the European Medicines Agency and the Food and Drug Administration, and extracted data. Setting - Thirty-two RCTs. Participants - A total of 6036 patients. Measurements - The primary outcome was total alcohol consumption (TAC). Other consumption outcomes and health outcomes were considered as secondary outcomes. Findings - No study provided direct comparisons between drugs. A risk of incomplete outcome data was identified in 26 studies (81%) and risk of selective outcome reporting in 17 (53%). Nalmefene [standardized mean difference (SMD) = -0.19, 95% confidence interval (CI) = -0.29, -0.10; I = 0%], baclofen (SMD = -1.00, 95% CI = -1.80, -0.19; one study) and topiramate (SMD = -0.77, 95% CI = -1.12, -0.42; I = 0%) showed superiority over placebo on TAC. No efficacy was observed for naltrexone or acamprosate. Similar results were observed for other consumption outcomes, except for baclofen (the favourable outcome on TAC was not reproduced). The number of withdrawals for safety reasons increased under nalmefene and naltrexone. No treatment demonstrated any harm reduction (no study was powered to explore health outcomes). Indirect comparisons suggested that topiramate was superior to nalmefene, naltrexone and acamprosate on consumption outcomes, but its safety profile is known to be poor. Conclusions - There is currently no high-grade evidence for pharmacological treatment to control drinking using nalmefene, naltrexone, acamprosate, baclofen or topiramate in patients with alcohol dependence or alcohol use disorder. Some treatments show low to medium efficacy in reducing drinking across a range of studies with a high risk of bias. None demonstrates any benefit on health outcomes.

Objectives The objectives of this cross-sectional study were to investigate dust exposure and respiratory health of workers in duck hatcheries in western France. Material and methods Ninety volunteer workers, who work in sorting rooms and/or incubation rooms, participated in exposure assessments and medical examinations. Medical examinations were performed by occupational health practitioners.They filled-in a questionnaire with the workers, followed by a lung function test on each worker. General characteristics and prevalence of chronic respiratory symptoms were described in each type of working rooms. Associations between symptoms and exposure (working room or dust level) were studied in GEE multivariate models. Results Overall prevalence of chronic respiratory symptoms (cough, phlegm) and chronic bronchitis were similar or lower than in the reference population. However, prevalence of these symptoms was higher for those working in sorting rooms, that were associated with an increased risk of respiratory symptoms and decreased lung function. Respirable dust was also significantly associated with an increased risk of respiratory symptoms. The prevalence of asthma and rhinitis were well above those in the reference population, but did not vary among working rooms. Descriptive data suggested an occupational origin for some cases. Conclusions Hatchery workers were at increased risk of compromised respiratory health due to dust exposure, particularly those who work in sorting rooms. Asthma and rhinitis were in excess in this population of workers. Thorough clinical examination of these workers should be performed and all exposures assessed.

Background: Cash transfer programs have the potential to improve dietary intake by improving accessibility to food. However, quantitative data on the impact of cash transfer programs on children's energy and nutrient intakes are lacking.Objective: The aim of this study was to evaluate the effect of seasonal unconditional cash transfers on children's energy, micro- and macronutrient, and food group intakes during the lean season in Burkina Faso.Methods: Within the framework of the MAM'Out (Moderate Acute Malnutrition Out) cluster-randomized controlled trial, two 24-h dietary recall surveys were conducted in July and August 2014. Daily energy and macro- and micronutrient intakes, breastfeeding practices, and food group consumption were analyzed for 322 children aged 14-27 mo from an intervention group (benefiting from unconditional cash transfer during the lean season in 2013 and 2014) and a control group by using mixed linear, logistic, and Poisson regression models or a γ-generalized linear model with log-link. A dietary diversity score was calculated on the basis of 7 food groups.Results: Unconditional cash transfers during the lean season improved the diets of rural children through a higher consumption of eggs (11.3 ± 1.55 compared with 3.25 ± 0.79 g; P < 0.001), fat (20.6 ± 0.80 compared with 16.5 ± 0.89 g; P < 0.01), and vitamin B-12 (0.40 ± 0.02 compared with 0.34 ± 0.02 mg; P < 0.001) compared with controls and higher proportions of children consuming dairy products (OR: 4.14; 95% CI: 1.48, 11.6; P < 0.05), flesh foods (OR: 2.09; 95% CI: 1.18, 3.70; P < 0.05), and iron-rich or iron-fortified foods (OR: 2.23; 95% CI: 1.20, 4.13; P < 0.05). No difference was found in energy intake between the 2 groups. The minimum dietary diversity of two-thirds of the children who benefited from cash transfers was adequate compared with only one-third in the control group (P < 0.001).Conclusions: Unconditional seasonal cash transfer increases intakes of high-nutritional-value foods in Burkinabe children aged 14-27 mo. As such, their use can be recommended in actions addressing children's dietary intake during the lean season. This trial was registered at clinicaltrials.gov as NCT01866124.

During pregnancy, mothers-to-be should adapt their diet to meet increases in nutrient requirements. Pregnant women appear to be keener to adopt healthier diets, but are not always successful. The objective of the present study was to determine whether a guided, stepwise and tailored dietary counselling programme, designed using an optimisation algorithm, could improve the nutrient adequacy of the diet of pregnant women, beyond generic guidelines. Pregnant women (n 80) who attended Notre-Dame-de-Bon-Secours Maternity Clinic were randomly allocated to the control or intervention arm. Dietary data were obtained twice from an online 3-d dietary record. The nutrient adequacy of the diet was calculated using the PANDiet score, a 100-point diet quality index adapted to the specific nutrient requirements for pregnancy. Women were supplied with generic dietary guidelines in a reference booklet. In the intervention arm, they also received nine sets of tailored dietary advice identified by an optimisation algorithm as best improving their PANDiet score. Pregnant women (n 78) completed the 12-week dietary follow-up. Initial PANDiet scores were similar in the control and intervention arms (60·4 (sd 7·3) v. 60·3 (sd 7·3), P = 0·92). The PANDiet score increased in the intervention arm (+3·6 (sd 9·3), P = 0·02) but not in the control arm (−0·3 (sd 7·3), P = 0·77), and these changes differed between arms (P = 0·04). In the intervention arm, there were improvements in the probabilities of adequacy for α-linolenic acid, thiamin, folate and cholesterol intakes (P < 0·05). Tailored dietary counselling using a computer-based algorithm is more effective than generic dietary counselling alone in improving the nutrient adequacy of the diet of French women in mid-pregnancy.

International audience; Meat consumption in Western countries is declining and, while the proportion of strict vegetarians remains low, intermediate diets such as flexitarianism have been developing in recent years. Our objectives were to identify the different levels of transition towards low-meat diets, characterize how these diets differ in terms of food intake, and identify whether attitudes and beliefs can explain these degrees of transition. In a representative survey of the French adult population conducted in 2018 (n = 2055), participants declared whether they followed a particular diet and completed a food frequency questionnaire on 29 food sources of protein and a questionnaire on their attitudes and beliefs regarding protein sources. We identified four dietary types based on these declarative data: vegetarians, flexitarians, pro-flexitarians and omnivores. The theory of planned behavior was used to predict meat intake and intentions to reduce meat intake. The sample contained 2.5% vegetarians, 6.3% flexitarians, 18.2% pro-flexitarians and 72.9% omnivores. The diet groups displayed specific dietary profiles and attitudinal scores. Compared with omnivores, pro-flexitarians consumed less red meat, more vegetables and legumes and were much more in agreement about the environmental impacts of meat. Compared with pro-flexitarians, flexitarians consumed less red meat and processed meat, and agreed much more about the health impacts of meat. Finally, versus flexitarians, vegetarians consumed almost no meat but far more legumes, nuts and seeds, and were much more sensitive to animal welfare issues. Attitudes, social norms and perceived behavioral control (PBC) predicted intentions to reduce meat consumption but attitude was the most important predictor. Intentions and PBC were both predictive of meat consumption. The dietary type related to the level of meat intake could be predicted by self-declared attitudes and beliefs regarding protein sources.

Background There is a current trend in Western countries toward increasing the intake of plant protein. A higher plant-protein intake has been associated with nutritional and health benefits, but these may depend on the pattern of plant-protein sources. Objective We hypothesized that the diversity of plant foods could be important to nutrient adequacy when increasing plant-protein intake in the diet. Methods Using data on 1341 adults (aged 18–64 y) from a representative French national dietary survey conducted in 2014–2015 (the third Individual and National Study on Food Consumption Survey—INCA3), we studied the links between plant-protein intake, dietary diversity (using various dimensions), and nutrient adequacy [assessed using the PANDiet (Probability of Adequate Nutrient Intake) scoring system, comprising adequacy (AS) and moderation (MS) subscores]. We simulated substituting plant-protein foods for animal-protein foods using different models of plant-protein diversity. Results We found that overall diet quality was weakly associated with total and protein diversity and more strongly with plant-protein diversity. Plant-protein intake was inversely associated with animal-protein intake, and positively with the PANDiet and MS, but not with the AS. Plant-protein intake displayed little diversity, mostly taking the form of grains (61% of plant-protein intake), and this diversity was even less marked under a higher plant-protein intake. Finally, modeled substitutions showed that reducing animal-protein intake increased the MS (by 32%) in a similar manner whichever plant protein was used for substitution, whereas it decreased the AS (by 20%) unless using a highly diversified plant-protein mix. These simulated improvements in overall adequacy included marked decreases in adequacy regarding certain nutrients that are typically of animal origin. Conclusions We conclude that in French adults the current pattern of plant-protein intake is hindering the nutritional benefits of a transition toward more plant protein, indicating that the consumption of plant-protein-based foods other than refined grains should be encouraged.

Background The intake of specific amino acids (AA) has been associated with cardiovascular health, but amino acids are consumed together as dietary protein. Here we investigated the association between identified patterns of amino acid intake and cardiovascular mortality. Methods A total of 2216 cardiovascular deaths among 79 838 men and women from the Adventist Health Study-2 were included in our analysis. Baseline dietary patterns based on the participants' amino acids intakes were derived by factor analysis. Using Cox regression analyses, we estimated multivariate-adjusted hazard ratios (HRs) adjusted for sociodemographic and lifestyle factors and other dietary components. Results Three patterns of amino acids were identified. Factor 1 was positively associated with cardiovascular disease (CVD) mortality [hazard ratio (HR)Q5-Q1: 1.62, 98.75% confidence interval (CI): 1.15, 2.28; P-trend Conclusions Indispensable AA have a positive and some non-indispensable AA have a negative, independent, strong association with the risk of cardiovascular mortality.

International audience; Promoting a more balanced animal/plant dietary protein ratio by changing portion sizes or introducing new foods is a promising means to improve diet quality, but little is known about the willingness of individuals to adopt such changes. Our objective was to assess the willingness to adopt dietary changes by these means. In a French cross-sectional study in 2018 (n = 2055), we analyzed the association between the willingness to eat smaller or larger portions or to introduce non-consumed protein foods and the current dietary patterns of individuals and their socio-demographic characteristics. These modifications had previously been identified as improving the nutrient adequacy of diets. Participants were more willing to eat smaller portion sizes than to introduce new foods and to eat larger portion sizes. The willingness for any modification varied depending on the food groups concerned. Participants were also more willing to eat larger portions and less willing to eat smaller portions when they were the most frequent consumers of the foods concerned. Participants were more willing to eat a new food if it was consumed in large quantities by individuals with a similar dietary pattern. This study underlines the importance of accounting for individual food habits when issuing nutritional recommendations.

International audience; Surveillance biopsies after renal transplantation remain debatable. To drive the decision of such intervention, we propose a predictive score of abnormal histology at 1-year post-transplantation, named 1-year Renal Biopsy Index (1-RBI). We studied 466 kidney recipients from the DIVAT cohort alive with a functioning graft and a surveillance biopsy at 1-year post-transplantation. Patients displaying abnormal histology (49%) (borderline, acute rejection, interstitial fibrosis and tubular atrophy [IFTA] grade 2 or 3, glomerulonephritis) were compared to the normal or subnormal (IFTA grade 1) histology group. Obtained from a lasso penalized logistic regression , the 1-RBI was composed of recipient gender, serum creatinine at 3, 6, and 12 month post-transplantation and anticlass II immunization at transplantation (internal validation: AUC = 0.71, 95% CI [0.53-0.83]; external validation: AUC = 0.62, 95% CI [0.58-0.66]). While we could not determinate a threshold able to identify patients at high chance of normal or subnormal histology, we estimated and validated a discriminating threshold capable of identifying a subgroup of 15% of the patients with a risk of abnormal histology higher than 80%. The 1-RBI is computable online at www.divat.fr. The 1-RBI could be a useful tool to standardize 1-year biopsy proposal and may for instance help to indicate one in case of high risk of abnormal histology.

Asymmetric and symmetric dimethylarginine (ADMA and SDMA, respectively) are risk factors for the cardiovascular and renal systems. There is a paucity of data in humans regarding variations of protein L-arginine (Arg) methylation leading to ADMA and SDMA. In this study, we introduced and used Arg dimethylation indices based on the creatinine-corrected urinary excretion of SDMA and ADMA, and its major metabolite dimethylamine (DMA). The main objective of the present study was to assess whether, and to which extent, a high-fat protein meal (HFM), a classical allostatic load eliciting various adverse effects, may contribute to Arg dimethylation in proteins in humans. Reliable gas chromatography&ndash, mass spectrometry methods were used to measure the concentration of ADMA, DMA, SDMA, and creatinine in spot urine samples collected before (0 h), and after (2, 4, 6 h) three HFM sessions in 10 healthy overweight individuals. At baseline, urinary ADMA, DMA, and SDMA excretion correlated positively with circulating TNF-&alpha, and IL-6. Arg dimethylation indices did not change postprandially. Our study shows that three HFMs do not contribute to Arg dimethylation in proteins. The proposed indices should be useful to determine extent and status of the whole-body Arg dimethylation in proteins in humans under various conditions.

Visio conférence; International audience; Objectives: The dietary shift from animal protein (AP) sources to plant protein (PP) sources is promoted for both environmental and health reasons. Indeed, PP are associated to lower cardiovascular and diabetes risks compared to AP, but the underlying mechanisms remain mostly unknown. Metabolomics, which has a unique ability to provide an integrative snapshot of the metabolic status of an individual, is a valuable tool to investigate the different metabolic pathways activated by AP or PP intake and to provide biomarkers of their metabolic effects. This scoping review aimed at gathering and analyzing the available data on the metabolomics signatures associated to PP or AP intake, for discussing the metabolic effects underlying these signatures and their potential implication for cardiometabolic health. Methods: We selected a total of 23 human studies comparing the urine, plasma or serum metabolomes associated to diets with contrasted AP and PP intakes, such as vegetarian and omnivore diets, and collected all discriminant metabolites across diets. Results: Out of the 447 discriminant metabolites, 44 were repeatedly reported across studies, amino acids (AA) and AA-related products accounting for a high proportion. Branch-chained amino acids (BCAA), aromatic amino acids (AAA), glutamate, short-chained acylcarnitines and Trimethylamine-N-Oxide (TMAO) were associated to AP while glycine was associated to PP intake. TCA cycle intermediates and products from AAA gut microbiota degradation were also often reported, but the direction of their associations with AP or PP remained unclear. As regard to their implication for cardiometabolic health, BCAA, AAA, glutamate, short-chained acylcarnitines and TMAO are known to be associated to increased risk while glycine is rather associated with a decreased risk.Conclusions: AP or PP intakes result in different metabolomics signatures, several metabolites being plausible candidates to at least partially explain their differential associations with cardiometabolic risk. Additional studies with a specific focus on protein type, deep dietary data and tight intake control are needed to better characterize the associated metabolic phenotype and understand how it could mediate AP or PP effects on cardiometabolic risk. Funding Sources INRAE

Background: Oral L-arginine supplements can have a beneficial effect on nitric oxide (NO)-related functions when subjects have cardiovascular disease risk factors. Objective: The study was designed to determine the utilization for NO synthesis of oral L-arginine as a function of the cardiometabolic risk and the speed of absorption by comparing immediate-release arginine (IR-Arg), as in supplements, and sustained-release arginine (SR-Arg), which mimics the slow release of dietary arginine. Methods: In a randomized, single-blind, 2-period crossover, controlled trial (1 wk of treatment, >2 wk of washout), using[N-15-(15)-N(guanidino)]-arginine for the first morning dose, we compared the bioavailability (secondary outcome) and utilization for NO synthesis (primary outcome) of 1.5 g IR- and SR-Arg 3 times/d in 12 healthy overweight [body mass index (BMI; in kg/m(2)): 25-30] adults with the hypertriglyceridemic waist phenotype [HTW; plasma triglycerides (TGs): >150 mg/dL; waist circumference: >94 cm (men) or >80 cm (women)] and 15 healthy control adults (CON; BMI: 18.5-25; no elevated TGs and waist circumference). Results: Plasma oral arginine areas under the curve were lower after supplementation with SR-Arg than with IR-Arg (112 +/- 52.3 and 142 +/- 50.8 mu mol . h/L; P < 0.01). The utilization of oral arginine for NO synthesis was 58% higher in HTW subjects than in CON subjects and higher with SR-Arg than with IR-Arg (P < 0.05 both), particularly in HTW subjects (group-by-treatment interaction, P < 0.05). In HTW subjects administered the SR form, utilization for NO synthesis was 32% higher than with the IR form and 87% higher than in CON subjects who were administered the SR form. Conclusion: In overweight adults with the HTW phenotype, a slow- compared with a fast-release form of oral arginine markedly favors the utilization of arginine for NO synthesis. The utilization of low-dose, slow-release arginine for NO synthesis is higher in overweight adults with the HTW phenotype than in healthy controls, suggesting that the sensitivity of NO synthesis to the dietary arginine supply increases with cardiometabolic risk. The trial was registered at clinicaltrials.gov as NCT02352740.

International audience; AbstractAlthough copper (Cu) is recognized as an essential trace element, uncertainties remain regarding Cu reference values for humans, as illustrated by discrepancies between recommendations issued by different national authorities. This review examines human studies published since 1990 on relationships between Cu intake, Cu balance, biomarkers of Cu status, and health. It points out several gaps and unresolved issues which make it difficult to assess Cu requirements. Results from balance studies suggest that daily intakes below 0.8 mg/day lead to net Cu losses, while net gains are consistently observed above 2.4 mg/day. However, because of an incomplete collection of losses in all studies, a precise estimation of Cu requirements cannot be derived from available data. Data regarding the relationship between Cu intake and potential biomarkers are either too preliminary or inconclusive because of low specificity or low sensitivity to change in dietary Cu over a wide range of intakes. Results from observation and intervention studies do not support a link between Cu and a risk of cardiovascular disease, cognitive decline, arthritis or cancer for intakes ranging from 0.6 to 3 mg/day, and limited evidence exists for impaired immune function in healthy subjects with a very low (0.38 mg/day) Cu intake. However, data from observation studies should be regarded with caution because of uncertainties regarding Cu concentration in various foods and water. Further studies that accurately evaluate Cu exposure based on reliable biomarkers of Cu status are needed.

International audience; Background : Patterns of protein food intake are undergoing a transition in Western countries, but little is known about how dietary changes to protein intake affect nutrient adequacy of the diet.Objectives : Our objective was to identify simple modifications to protein food intake that can gradually increase overall nutrient adequacy.Methods : We identified patterns of dietary protein intake in 1678 adults from a representative French national dietary survey. For each individual, we identified the increase in portion size of 1 protein food paired with a decrease in the portion size of another protein food that would best increase nutrient adequacy (using PANDiet probabilistic scoring). Then, such an optimum simple dual change was iterated 20 times for each individual according to 2 scenarios, either by manipulating the intake of foods already consumed [scenario 1 (S1)] or by enabling the introduction of foods consumed by >10% of individuals with the same protein pattern [scenario 2 (S2)]. Results : The optimum stepwise changes to protein intake primarily consisted of reducing portions of deli meats (both scenarios), sandwiches, and cheese (S2), while increasing portions of fatty fish and lean poultry (both scenarios) and legumes (S2). However, these changes differed depending on the initial dietary protein pattern of the individual. For example, in S2, legume intake increased among “poultry” and “fish” eaters only and low-fat meat among “take-away eaters” and “milk drinkers” only. The improvements in overall nutrient adequacy were similar among the different initial dietary patterns, but this was the result of changes to the adequacy of different specific nutrients. Conclusion : Beyond generic changes to protein intake in the entire French adult population, the initial dietary protein pattern is key to identifying the food groups most likely to improve overall nutrient adequacy and the profile of nutrients whose adequacy can easily be increased.

ObjectiveTo evaluate the impact of multiannual, seasonal unconditional cash transfers (UCT) provided within the Moderate Acute Malnutrition Out (MAM’Out) research project on households’ food security and children’s and caregivers’ dietary diversity.DesignA two-arm cluster-randomized controlled trial with sixteen villages in the intervention group and sixteen others in the control group. A monthly allowance of 10 000 XOF was transferred to caregivers of eligible children via a personal mobile phone account from July to November 2013 and 2014.SettingTapoa province in the eastern region of Burkina Faso.ParticipantsData on household food access (monthly adequate household food provisioning (MAHFP); household food insecurity access scale (HFIAS)) and maternal and child dietary diversity were analysed for 1143 households, 1219 caregivers of reproductive age (15–49 years) and 1247 under-5 children from both intervention and control groups.ResultsThe mean women dietary diversity score in intervention caregivers and the mean dietary diversity score (DDS) in intervention children with inadequate minimum DDS at baseline were respectively 7 % (95 % CI 2, 11 %;P= 0·002) and 17 % (95 % CI 11, 23 %;PP= 0·565) and MAHFP (relative risk = 0·98; 95 % CI 0·96, 1·01;P= 0·426).ConclusionsMultiannual, seasonalUCT increased dietary diversity in children and their caregivers. They can be recommended in actions aiming to improve maternal and child diet diversity.

White lupin (Lupinus albus L.) is a legume that produces seeds recognized for their high protein content and good nutritional value (lowest glycemic index of all grains, high dietary fiber content, and zero gluten or starch)1–5. White lupin can form nitrogen-fixing nodules but has lost the ability to form mycorrhizal symbiosis with fungi6. Nevertheless, its root system is well adapted to poor soils: it produces cluster roots, constituted of dozens of determinate lateral roots that improve soil exploration and phosphate remobilization7. As phosphate is a limited resource that comes from rock reserves8, the production of cluster roots is a trait of interest to improve fertilizers efficiency. Using long reads sequencing technologies, we provide a high-quality genome sequence of a modern variety of white lupin (2n=50, 451 Mb), as well asde novoassemblies of a landrace and a wild relative. We describe how domestication impacted soil exploration capacity through the early establishment of lateral and cluster roots. We identify theAPETALA2transcription factorLaPUCHI-1, homolog of the Arabidopsis morphogenesis coordinator9, as a potential regulator of this trait. Our high-quality genome and companion genomic and transcriptomic resources enable the development of modern breeding strategies to increase and stabilize yield and to develop new varieties with reduced allergenic properties (caused by conglutins10), which would favor the deployment of this promising culture.

International audience; An abstract is not available for this content

International audience; This study is devoted to investigate the influence of a knee orthosis for human walking by using a mathematical model for a 7-links planar biped-composed with two identical legs, two feet and one trunk-with an orthosis attached to both thigh and calf, during walking. In the first part, we design a cyclic walking gait in the sagittal plane for human without the orthosis. The second part we consider that the human looses his muscular possibilities in one of his knees. To overcome his handicap the human is equipped of a knee orthosis. We analyse the positive effect of the orthosis over the assisted knee to track the previous designed reference trajectory. By using at each time an optimisation algorithm, we minimise the torques provided by the human. The numerical tests confirm the possibility to reduce the torque produced in the disabled knee. The next step is to take into account explicitly an information from EMG signal during a walking to modulate the power of the orthosis.

BACKGROUND & AIMS: In Europe, hepatitis C virus (HCV) screening still targets people at high risk of infection. We aim to determine the cost-effectiveness of expanded HCV screening in France. METHODS: A Markov model simulated chronic hepatitis C (CHC) prevalence, incidence of events, quality-adjusted life years (QALYs), costs and incremental cost-effectiveness ratio (ICER) in the French general population, aged 18 to 80 years, undiagnosed for CHC for different strategies: S1 = current strategy targeting the at risk population; S2 = S1 and all men between 18 and 59 years; S3 = S1 and all individuals between 40 and 59 years; S4 = S1 and all individuals between 40 and 80 years; S5 = all individuals between 18 and 80 years (universal screening). Once CHC was diagnosed, treatment was initiated either to patients with fibrosis stage ≥F2 or regardless of fibrosis. Data were extracted from published literature, a national prevalence survey, and a previously published mathematical model. ICER were interpreted based on one or three times French GDP per capita (€32,800). RESULTS: Universal screening led to the lowest prevalence of CHC and incidence of events, regardless of treatment initiation. When considering treatment initiation to patients with fibrosis ≥F2, targeting all people aged 40-80 was the only cost-effective strategy at both thresholds (€26,100/QALY). When we considered treatment for all, although universal screening of all individuals aged 18-80 is associated with the highest costs, it is more effective than targeting all people aged 40-80, and cost-effective at both thresholds (€31,100/QALY). CONCLUSIONS: In France, universal screening is the most effective screening strategy for HCV. Universal screening is cost-effective when treatment is initiated regardless of fibrosis stage. From an individual and especially from a societal perspective of HCV eradication, this strategy should be implemented. LAY SUMMARY: In the context of highly effective and well tolerated therapies for hepatitis C virus that are now recommended for all patients, a reassessment of hepatitis C screening strategies is needed. An effectiveness and cost-effectiveness study of different strategies targeting either the at-risk population, specific ages or all individuals was performed. In France, universal screening is the most effective strategy and is cost-effective when treatment is initiated regardless of fibrosis stage. From an individual and especially from a societal perspective of hepatitis C virus eradication, this strategy should be implemented.

Animal tissues are naturally 15N enriched relative to their diet and the extent of this difference (Δ15Nanimal-diet) has been correlated to the efficiency of N assimilation in different species. The rationale is that transamination and deamination enzymes, involved in amino acid metabolism are likely to preferentially convert amino groups containing 14N over 15N. However, in ruminants the contribution of rumen bacterial metabolism relative to animal tissues metabolism to naturally enrich animal proteins in terms of 15N has been not assessed yet. The objective of this study was to assess the impact of rumen and digestion processes on the relationship between Δ15Nanimal-diet and efficiency of N utilization for milk protein yield (milk N efficiency (MNE); milk N yield/N intake) as well as the relationship between the 15N natural abundance of rumen bacteria and the efficiency of N use at the rumen level. Solid- and liquid-associated rumen bacteria, duodenal digesta, feces and plasma proteins were obtained (n=16) from four lactating Holstein cows fed four different diets formulated at two metabolizable protein supplies (80% v. 110% of protein requirements) crossed by two different dietary energy source (diets rich in starch v. fiber). We measured the isotopic N fractionation between animal and diet (Δ15Nanimal-diet) in these different body pools. The Δ15Nanimal-diet was negatively correlated with MNE when measured in solid-associated rumen bacteria, duodenal digesta, feces and plasma proteins, with the strongest correlation found for the latter. However, our results showed a very weak 15N enrichment of duodenal digesta (Δ15Nduodenal digesta-diet mean value=0.42) compared with that observed in plasma proteins (Δ15Nplasma protein-diet mean value=2.41). These data support the idea that most of the isotopic N fractionation observed in ruminant proteins (Δ15Nplasma protein-diet) has a metabolic origin with very little direct impact of the overall digestion process on the existing relationship between Δ15Nplasma protein-diet and MNE. The 15N natural abundance of rumen bacteria was not related to either rumen N efficiency (microbial N/available N) or digestive N efficiency (metabolizable protein supply/CP intake), but showing a modest positive correlation with rumen ammonia concentration. When using diets not exceeding recommended protein levels, the contribution of rumen bacteria and digestion to the isotopic N fractionation between animal proteins and diet is low. In our conditions, most of the isotopic N fractionation (Δ15Nplasma protein-diet) could have a metabolic origin, but more studies are warranted to confirm this point with different diets and approaches.

International audience; Protein food intake appears to partially structure dietary patterns, as most current emergent diets (e.g., vegetarian and flexitarian) can be described according to their levels of specific protein sources. However, few data are available on dietary protein patterns in the general population and their association with nutrient adequacy. Based on protein food intake data concerning 1678 adults from a representative French national dietary survey, and non-negative-matrix factorization followed by cluster analysis, we were able to identify distinctive dietary protein patterns and compare their nutrient adequacy (using PANDiet probabilistic scoring). The findings revealed eight patterns that clearly discriminate protein intakes and were characterized by the intakes of one or more specific protein foods: ‘Processed meat’, ‘Poultry’, ‘Pork’, ‘Traditional’, ‘Milk’, ‘Take-away’, ‘Beef’ and ‘Fish’. ‘Fish eaters’ and ‘Milk drinkers’ had the highest overall nutrient adequacy, whereas that of ‘Pork’ and ‘Take-away eaters’ was the lowest. Nutrient adequacy could often be accounted for by the characteristics of the food contributing to protein intake: ‘Meat eaters’ had high probability of adequacy for iron and zinc, for example. We concluded that protein patterns constitute strong elements in the background structure of the dietary intake and are associated with the nutrient profile that they convey.

International audience; We recently found that renal carbonic anhydrase (CA) is involved in the reabsorption of inorganic nitrite (NO2−), an abundant reservoir of nitric oxide (NO) in tissues and cells. Impaired NO synthesis in the endothelium and decreased NO bioavailability in the circulation are considered major contributors to the development and progression of renal and cardiovascular diseases in different conditions including diabetes. Isolated human and bovine erythrocytic CAII and CAIV can convert nitrite to nitrous acid (HONO) and its anhydride N2O3 which, in the presence of thiols (RSH), are further converted to S-nitrosothiols (RSNO) and NO. Thus, CA may be responsible both for the homeostasis of nitrite and for its bioactivation to RSNO/NO. We hypothesized that enhanced excretion of nitrite in the urine may contribute to NO-related dysfunctions in the renal and cardiovascular systems, and proposed the urinary nitrate-to-nitrite molar ratio, i.e., UNOxR, as a measure of renal CA-dependent excretion of nitrite. Based on results from clinical and experimental animal studies, here, we report on a first evaluation of UNOxR. We determined UNOxR values in preterm neonates, healthy children, and adults, in children suffering from type 1 diabetes mellitus (T1DM) or Duchenne muscular dystrophy (DMD), in elderly subjects suffering from chronic rheumatic diseases, type 2 diabetes mellitus (T2DM), coronary artery disease (CAD), or peripheral arterial occlusive disease (PAOD). We also determined UNOxR values in healthy young men who ingested isosorbide dinitrate (ISDN), pentaerythrityl tetranitrate (PETN), or inorganic nitrate. In addition, we tested the utility of UNOxR in two animal models, i.e., the LEW.1AR1-iddm rat, an animal model of human T1DM, and the APOE*3-Leiden.CETP mice, a model of human dyslipidemia. Mean UNOxR values were lower in adult patients with rheumatic diseases (187) and in T2DM patients of the DALI study (74) as compared to healthy elderly adults (660) and healthy young men (1500). The intra- and inter-variabilities of UNOxR were of the order of 50% in young and elderly healthy subjects. UNOxR values were lower in black compared to white boys (314 vs. 483, P = 0.007), which is in line with reported lower NO bioavailability in black ethnicity. Mean UNOxR values were lower in DMD (424) compared to healthy (730) children, but they were higher in T1DM children (1192). ISDN (3 × 30 mg) decreased stronger UNOxR compared to PETN (3 × 80 mg) after 1 day (P = 0.046) and after 5 days (P = 0.0016) of oral administration of therapeutically equivalent doses. In healthy young men who ingested NaNO3 (0.1 mmol/kg/d), UNOxR was higher than in those who ingested the same dose of NaCl (1709 vs. 369). In LEW.1AR1-iddm rats, mean UNOxR values were lower than in healthy rats (198 vs. 308) and comparable to those in APOE*3-Leiden.CETP mice (151).

The poultry reservoir, especially broiler meat, is generally recognized as one of the most-important sources for human Campylobacteriosis. The measures to control Campylobacter targeted essentially the primary production level. The aim of this work was to evaluate the effectiveness of different treatments against natural Campylobacter colonization in a French experimental farm of free-range broilers during the whole rearing period. Five commercial products and a combination of two of them were tested and all the products were added to feed or to water at the dose recommended by the suppliers. Campylobacter loads in caeca and on carcasses of broilers at the slaughter were determined by culture methods. Natural contamination of the flock occurred at the end of the indoor rearing period between day 35 and day 42. At day 42, the multispecies probiotic added to the feed reduced the contamination of 0.55 log10 CFU/g (p = 0.02) but was not significant (p > 0.05) at the end of rearing at day 78. However, another treatment, a combination of a cation exchange clay-based product in feed and an organic acid mixture (formic acid, sodium formate, lactic acid, propionic acid) in water, led to a slight but significant reduction of 0.82 ± 0.25 log10 CFU/g (p = 0.02) compared to the control group at day 78. Testing this combination in field conditions in several flocks is needed to determine if it is biologically relevant and if it could be a valuable measure to reduce Campylobacter in broiler flocks.

A randomized controlled trial (RCT) was carried to evaluate the effect of a feed additive on Campylobacter contamination of broilers reared in commercial conditions. Twenty-four broiler flocks naturally contaminated with Campylobacter were enrolled in the RCT: 12 were assigned to a control group (C) fed with a conventional finishing feed from 4 weeks of age to slaughter (around 35 days), and the other group of 12 flocks (S) was fed with a finishing feed supplemented with 250 ppm of a patented feed additive (an ion-exchanged clay compound) previously proven to reduce Campylobacter contamination in broiler caeca under experimental conditions. Enumeration of Campylobacter colonies in caeca (8 per flock) was carried out following ISO standards before feed distribution and at slaughter. Before treatment, the caecal Campylobacter load tended to be lower in C flocks (7.1 ± 1.9 log CFU/g, CI95% [6.6-7.5]) than in S flocks (7.7 ± 1.0 log UFC/g, CI95% [7.5-7.9]) (p = .05). At slaughter, the bacterial load was similar in the S (7.7 ± 1.0 log CFU/g, CI95% [7.5-7.9]) and C groups (7.5 ± 1.2 log CFU/g, CI95% [7.2-7.8]) (p = .73). Therefore, the feed additive had no significant effect on the caecal Campylobacter load at slaughter under the tested conditions. The logistical constraints inherent in field trials and the natural variability of Campylobacter contamination in naturally infected broiler flocks make it difficult to reproduce experimental results in in situ farm conditions. RCT testing of an intervention strategy in commercial situation is therefore a key step in evaluating pre-harvest interventions against food-borne pathogens.

Background Acute malnutrition is a public health issue worldwide, and particularly in the Eastern region of Burkina Faso. Following a needs assessment, unconditional seasonal, multiannual cash transfers were implemented as a safety net to prevent childhood undernutrition. The objectives of this study were to explore the types of purchases made by beneficiaries of this cash transfer program and to understand the perceived effects of and changes induced by regular cash transfers in the daily lives of women, and at the household and community level. Methods The design of this study was a two-arm cluster randomized controlled trial. Qualitative data were collected each month during the cash transfer period for two years, leading to a total of more than 300 interviews and focus group discussions with various participants: beneficiary mothers, heads of households, mothers-in-law, co-wives, key members of the community, and participants of the control group. Results The two main types of expenses reported were food and health care for the child and the whole family. The program was also associated with positive perceived changes at the household level, mainly related to gender equality and improvement of women’s status, and has promoted an increase in dignity and social integration of the poorest at the community level through cash sharing. Unexpected effects of this program included some women planning new pregnancies and some individuals not expecting the transfers to end. Conclusion Although the transfers were unconditional, the cash was mainly used to improve the children’s and households’ food security and health, which correspond to two main underlying causes of undernutrition. Therefore, spending mainly in these areas can help to prevent undernutrition in children. Trial registration ClinicalTrials.gov, identifier: NCT01866124, registered May 7, 2013. Electronic supplementary material The online version of this article (doi:10.1186/s12889-017-4453-y) contains supplementary material, which is available to authorized users.

International audience; Background: Limited evidence is available on the impact that unconditional cash transfer (UCT) programs can have on child nutrition, particularly in West Africa, where child undernutrition is still a public health challenge.Objective: This study examined the impact of a multiannual, seasonal UCT program to reduce the occurrence of wasting (weight-for-height, midupper arm circumference), stunting (height-for-age), and morbidity among children 0.05) in children's anthropometric measurements and stunting between the 2 groups at the end point. However, children in the intervention group had a lower risk [21% (95% CI: 18.6%, 21.3%); P < 0.001] of self-reported respiratory tract infections than did children in the control group.Conclusions: We found that seasonal UCTs in the framework of safety nets did not result in a significant decrease in the incidence of acute malnutrition among children in Tapoa Province. Cash transfers combined with complementary interventions targeted to child nutrition and health should be investigated further. This trial was registered at clinicaltrials.gov as NCT01866124.

International audience; A downward trend in animal protein (AP) intake has been observed in western countries over the last decade and the effects of such a transition on protein adequacy remain debatable. Using the probability approach and diet modeling with data on 1678 adults from a representative French national dietary survey, we studied the sensitivity of the adequacy of protein and amino acid intakes to changes in animal:plant protein. We simulated the gradual substitution of AP with different mixtures of plant protein (PP), containing various proportions of PP already consumed and legumes, nuts and seeds (LNS). We found that protein and amino acid intakes met dietary requirements in virtually the entire population studied. Up to 50% of PP in diets, protein and amino acid intakes were adequate in all models. From 50%, protein inadequacy was primary due to protein quantity, and from 70%, to protein quality (as lysine inadequacy). The introduction of LNS in the mixture substituting AP led to adequate protein intakes for higher percentages of PP. An increase in PP based on the current pattern of plant protein sources, low in protein:energy, could lead to inadequate protein intake, but the contribution of LNS ensures the safety of a further transition.

Poupin N, Huneau J, Mariotti F, Tome D, Bos C, Fouillet H. Isotopic and modeling investigation of long-term protein turnover in rat tissues. Am J Physiol Regul Integr Comp Physiol 304: R218-R231, 2013. First published November 7, 2012; doi:10.1152/ajpregu.00310.2012.-Fractional synthesis rates (FSR) of tissue proteins (P) are usually measured using labeled amino acid (AA) tracer methods over short periods of time under acute, particular conditions. By combining the long-term and non-steady-state N-15 labeling of AA and P tissue fractions with compartmental modeling, we have developed a new isotopic approach to investigate the degree of compartmentation of P turnover in tissues and to estimate long-term FSR values under sustained and averaged nutritional and physiological conditions. We measured the rise-to-plateau kinetics of nitrogen isotopic enrichments (delta N-15) in the AA and P fractions of various tissues in rats for 2 mo following a slight increase in diet delta N-15. Using these delta N-15 kinetics and a numerical method based on a two-compartment model, we determined reliable FSR estimates for tissues in which P turnover is adequately represented by such a simple precursor-product model. This was the case for kidney, liver, plasma, and muscle, where FSR estimates were 103, 101, 58, and 11%/day, respectively. Conversely, we identified tissues, namely, skin and small intestine, where P turnover proved to be too complex to be represented by a simple two-compartment model, evidencing the higher level of subcompartmentation of the P and/or AA metabolism in these tissues. The present results support the value of this new approach in gaining cognitive and practical insights into tissue P turnover and propose new and integrated FSR values over all individual precursor AA and all diurnal variations in P kinetics.