Narrative Review of Effects of Glucagon-Like Peptide-1 Receptor Agonists on Bone Health in People Living with Obesity.

Glucagon-like peptide-1 Receptor agonists (GLP-1Ras) such as liraglutide and semaglutide have been recently approved as medications for chronic weight management in people living with obesity (PwO); GLP-1 may enhance bone metabolism and improve bone quality. However, the effects of GLP-1Ras on skeletal health remain to be determined and that's the purpose of this narrative review. Nevertheless, bone consequences of intentional weight loss interventions in PwO are well known: (i) significant weight loss induced by caloric restriction and bariatric surgery results in accelerated bone turnover and bone loss, and (ii) unlike caloric restriction interventions, PwO experience a substantial deterioration in bone microarchitecture and strength associated with an increased risk of fracture after bariatric surgery especially malabsorptive procedures. Liraglutide seems to have a positive effect on bone material properties despite significant weight loss in several rodent models. However, most of positive effects on bone mineral density and microarchitecture were observed at concentration much higher than approved for obesity care in humans. No data have been reported in preclinical models with semaglutide. The current evidence of the effects of GLP-1Ra on bone health in PwO is limited. Indeed, studies on the use of GLP-1Ra mostly included patients with diabetes who were administered a dose used in this condition, did not have adequate bone parameters as primary endpoints, and had short follow-up periods. Further studies are needed to investigate the bone impact of GLP-1Ra, dual- and triple-receptor agonists for GLP-1, glucose-dependent insulin releasing polypeptide (GIP), and glucagon in PwO.

Environmental impact and nutritional quality of adult diet in France based on fruit and vegetable intakes.

PURPOSE: To describe the nutritional quality and environmental impact of self-selected diets of adults in France in relation to their fruit and vegetable (FV) intakes. METHODS: Estimates of food and nutrient intakes were taken from the national INCA3 Survey on food intakes carried out in France in 2014-2015. The population (n = 2121 adults) was split into five quintiles of FV intakes, in g/d (Q1 representing the lowest intake, and Q5 the highest). The nutritional quality of diets was assessed through 4 indicators: mean adequacy ratio (MAR), solid energy density, mean excess ratio (MER) and Programme National Nutrition Santé guideline score 2 (PNNS-GS2). The environmental impacts were measured with environmental footprint (EF) scores and 4 additional indicators: climate change, ozone depletion, fine particulate matter and water use. Indicators were compared between quintiles. Analysis was conducted on diets adjusted to 2000 kcal. RESULTS: MAR and PNNS-GS2 increased with increased FV quintiles, while solid energy density decreased. Fibre, potassium, vitamin B9 and vitamin C densities increased with increasing FV intakes. Climate change, ozone depletion and fine particulate matter impacts of diets decreased with increasing quintiles of FV consumption. Conversely, water use impact increased. CONCLUSION: Higher intake of FV is associated with higher nutritional quality of diets and lower environmental impact, except for water use. Given the benefits of fruit and vegetables for human health and the environment, their negative impact on water use could be improved by working on the agricultural upstream, rather than by changing individuals' food choices and reducing their consumption.

Infant growth and tolerance with a formula based on novel native demineralized whey: A randomized double-blind pilot study.

OBJECTIVES: The aim of the study was to evaluate the effects on infant growth and tolerance of a Test infant formula based on a novel whey extraction and demineralization process, compared to a Standard formula and a breastfed reference arm. METHODS: Healthy term infants (n = 61) aged up to 21 days were randomized to Test or Control formula. A breastfed group (n = 39) served as a reference. Growth, tolerance, adverse events, and sleep were evaluated every month until 6 months of age. Plasma amino-acid concentrations at 3 months of age were measured in a subgroup population. RESULTS: Growth curves of all infants globally agreed with World Health Organization standards across the 6-months period study. Regarding tolerance, no difference between the formula-fed groups was observed on daily number of crying episodes, intensity or time to onset of regurgitations, and stool frequency or consistency, except at 5 months with infants in the Control group having more watery stools. Plasma concentration of some amino acids differed between the groups, especially tryptophan concentration which was higher in infants fed with the Test formula. In parallel, total sleep duration was longer in these infants at 2, 3, and 5 months of age, corresponding to an increase in daytime sleep. CONCLUSIONS: Test formula supported an adequate infant growth from birth to 6 months of age and was well-tolerated by all infants. An increase in total sleep at several months was also observed with the Test formula.

Comparison of pesticide residue and specific nutrient levels in peeled and unpeeled apples.

BACKGROUND: Studies have shown that the consumption of apples has a beneficial effect on cardiovascular diseases and some cancers, largely as a result of their micronutrient and phytoconstituent contents. Apple peel not only contains more polyphenols than the flesh, but also is likely to contain pesticide residues. The present study aimed to compare the contents of certain micronutrients and residual pesticide levels in peeled and unpeeled apples. RESULTS: Peeled apples contained fewer pesticide residues at lower concentrations than unpeeled apples. However, whether samples were peeled or not, the exposure values for pesticide residues in apples never exceeded the acceptable daily intake (ADI), but ranged between 0.04% and 2.10% of the ADI in adults for food intake estimated at the 95th percentile (277 g per person per day). Determination of polyphenol, fibre, magnesium and vitamin C levels showed that the nutritional differences observed between peeled and unpeeled apples were marginal. CONCLUSION: The consumption of apples, such as the apples tested in the present study, results in an exposure to pesticides that is low for unpeeled apples, and lower for peeled apples. Moreover, there was no significant loss of nutritional value from eating peeled apples based on the nutrients investigated. © 2022 Society of Chemical Industry.

Processing in the food chain: do cereals have to be processed to add value to the human diet?

Cereals and cereal products have a long history of use by humans. Recently, there have been some discussions regarding level of processing as a descriptor to define food products, including cereal-based foods. This has led to a somewhat emotional debate on food processing. Given the widespread inclusion of cereals in the diet, this review highlights the history of cereal processing as well as their consumption by humans. It provides an evidence-based discussion on their production, contribution to human nutrition, benefits and disadvantages. The present review illustrates the impact of processing on nutrients, as well as non-nutrients specifically in bread and ready-to-eat breakfast cereals (RTEC), two cereal-based foods which are widely consumed and integral parts of food-based dietary guidelines globally. As a category, most cereals must be processed in some way to enable consumption by humans as we are not equipped to survive exclusively on raw grains. Even thousands of years ago, the processing of cereals was a common practice by humans, turning raw grains into palatable, safe and nutritious foods. Modern processes for cereal-based products are efficient in providing safe and good-quality products to satisfy population needs, as well as helping to meet consumer expectations by providing a range of foods that allows for a varied and balanced diet. Today, RTEC and bread make significant contributions to dietary energy and nutrient requirements and underpin food-based dietary guidance globally. They have been positively linked with intake of dietary fibre, vitamins and minerals, especially when consumed as whole grain.

The Contribution of Modern Margarine and Fat Spreads to Dietary Fat Intake.

The study of dietary fat consumption and its resultant effects on human health has been one of the most investigated topics in the field of human nutrition. Based on the results obtained from such studies, specific dietary recommendations on fat intake (both in terms of quantity and quality) have been established by health organizations around the globe. Among the various food industry sectors, the margarine manufacturers have also responded to these guidelines and now offer improved formulations with a desirable balance of fat contents and fat types. The main aim of this article is to provide an overview on how these modern margarines can contribute towards reaching the dietary guidelines relating to fat intake. In particular, the dietary recommendations with respect to the specific fatty acid types are comprehensively detailed along with an emphasis on the role of modern margarines in providing balanced fat types (more polyunsaturated fats, less saturated fats and a near-complete absence of trans fats) in the daily diet.

Incorporation of lutein and docosahexaenoic acid from dietary microalgae into the retina in quail.

Lutein and docosahexaenoic acid (DHA) are associated with the prevention of age-related macular degeneration (AMD). Since microalgae are potent natural sources of these nutrients, their nutritional value should be evaluated based on the bioavailability of lutein and DHA for the retina via the plasmatic compartment. In this study, quail were fed for 5 months either with a diet supplemented or deprived with microalgae rich in lutein and DHA. In the microalgae-fed group, the retinal concentrations of lutein and zeaxanthin gradually increased whereas in plasma, these compounds started to increase from the first month of supplementation. We also observed a significant increase in retinal and plasmatic levels of DHA in the microalgae-fed group. In conclusion, the plasmatic and retinal contents of lutein and DHA were significantly increased in quail fed with lutein- and DHA-rich microalgae. Food fortification with microalgae may be an innovative way to increase lutein and DHA consumption in humans.

Effect on blood lipids of two daily servings of Camembert cheese. An intervention trial in mildly hypercholesterolemic subjects.

As a concentrated source of saturated fat, cheese consumption is considered to be associated with increased cholesterolemia and generally forbidden in dietary guidelines for adults with hypercholesterolemia. The aim of this study was to evaluate the impact of saturated fatty acids on lipid parameters and blood pressure with regards to different types of dairy products: Camembert and full-fat yoghurt. One-hundred and fifty-nine moderate hypercholesterolemic subjects without treatment were instructed to consume two full-fat yoghurts (2 × 125 g) per day for 3 weeks (run-in period) and then for a further period of 5 weeks, either two full-fat yoghurts or two 30 g servings of Camembert cheese per day. We observed that over the 5-week daily consumption of two servings of Camembert cheese, blood pressure and serum lipids did not change in moderate hypercholesterolemic subjects. These results suggest that fermented cheese such as Camembert could be consumed daily without affecting serum lipids or blood pressure.

Description of a large family with autosomal dominant hypercholesterolemia associated with the APOE p.Leu167del mutation.

Apolipoprotein (apo) E mutants are associated with type III hyperlipoproteinemia characterized by high cholesterol and triglycerides levels. Autosomal dominant hypercholesterolemia (ADH), due to the mutations in the LDLR, APOB, or PCSK9 genes, is characterized by an isolated elevation of cholesterol due to the high levels of low-density lipoproteins (LDLs). We now report an exceptionally large family including 14 members with ADH. Through genome-wide mapping, analysis of regional/functional candidate genes, and whole exome sequencing, we identified a mutation in the APOE gene, c.500_502delTCC/p.Leu167del, previously reported associated with sea-blue histiocytosis and familial combined hyperlipidemia. We confirmed the involvement of the APOE p.Leu167del in ADH, with (1) a predicted destabilization of an alpha-helix in the binding domain, (2) a decreased apo E level in LDLs, and (3) a decreased catabolism of LDLs. Our results show that mutations in the APOE gene can be associated with bona fide ADH.

Mutations in PCSK9 cause autosomal dominant hypercholesterolemia.

Autosomal dominant hypercholesterolemia (ADH; OMIM144400), a risk factor for coronary heart disease, is characterized by an increase in low-density lipoprotein cholesterol levels that is associated with mutations in the genes LDLR (encoding low-density lipoprotein receptor) or APOB (encoding apolipoprotein B). We mapped a third locus associated with ADH, HCHOLA3 at 1p32, and now report two mutations in the gene PCSK9 (encoding proprotein convertase subtilisin/kexin type 9) that cause ADH. PCSK9 encodes NARC-1 (neural apoptosis regulated convertase), a newly identified human subtilase that is highly expressed in the liver and contributes to cholesterol homeostasis.

Dietary recommendations in the prevention and treatment of osteoporosis.

INTRODUCTION: This article presents the initial recommendations of the French Rheumatology Society (Société Française de Rhumatologie - SFR) and the Osteoporosis Research and Information Group (Groupe de Recherche et d'Informations sur les Ostéoporoses - GRIO) on the role of diet in the prevention and treatment of osteoporosis. METHODS: The recommendations were produced by a working group composed of rheumatologists, physician nutrition specialists and a geriatrician. Fifteen (15) questions pertaining to "daily practices" were preselected by the working group. For the literature review, the working group focussed mainly on the effects of diet on bone mineral density (BMD) and fractures, and primarily on meta-analyses of longitudinal studies and dietary intervention studies. RESULTS: A Mediterranean-type diet and the daily consumption of 2 to 3 dairy products are recommended. Together, these provide the calcium and "high quality" protein required to maintain a normal calcium-phosphorus balance and bone metabolism, and are associated with lower fracture risk. Conversely, unbalanced Western diets, vegan diets, weight-loss diets in non-overweight individuals, alcohol consumption and daily consumption of sodas are advised against. In terms of the beneficial effects on bone mineral density and fracture risk, current scientific data are either insufficient or too divergent to recommend increasing or restricting the consumption of tea or coffee, vitamins other than vitamin D, vitamin D-enriched or phytoestrogen-rich foods, calcium-enriched plant-based beverages, oral nutritional supplements, or dietary sources of prebiotics and probiotics. CONCLUSIONS: These are the first set of recommendations addressing the role of diet in the prevention and treatment of osteoporosis. More research is necessary to direct and support guidelines.

Xylo-oligosaccharide (XOS) in combination with inulin modulates both the intestinal environment and immune status in healthy subjects, while XOS alone only shows prebiotic properties.

The purpose of the present study was to establish the prebiotic effect of a new xylo-oligosaccharide (XOS) and of an inulin-and-XOS mixture (INU-XOS) and to determine their effect on endotoxaemia (lipopolysaccharides (LPS)) and immune parameters. In this randomised, parallel, placebo-controlled, double-blind study, sixty healthy volunteers were randomly assigned to three groups, receiving either 5 g XOS, INU-XOS (3 g inulin +1 g XOS) or an equivalent weight of wheat maltodextrin (placebo) during 4 weeks. Faecal samples were collected to assess the effects of these products on microbiota, as well as SCFA composition, enzymatic activities and secretory IgA production. Circulating LPS was measured in plasma samples, and whole blood was incubated with LPS to measure cytokine expression. Consumption of XOS alone increased the faecal concentrations of Bifidobacterium and butyrate and activities of α-glucosidase and ß-glucuronidase, while decreasing the concentrations of acetate and p-cresol. Consumption of XOS in combination with inulin did not decrease the concentrations of acetate and p-cresol, but increased in addition the faecal concentrations of total SCFA and propionate. Furthermore, consumption of XOS in combination with inulin decreased LPS concentrations in blood and attenuated LPS-induced increases in gene expression in IL-1ß and LPS-induced decreases in gene expression in IL-13 in blood. In conclusion, consumption of XOS alone or in combination with inulin results in beneficial albeit different changes in the intestinal microbiome on a high-fat diet. In addition, consumption of XOS in combination with inulin attenuates the proinflammatory effects of a high-fat diet in the blood of healthy subjects.

Cholecalciferol (vitamin D3) must not be considered as an endocrine disruptor / Le cholécalciférol (la vitamine D3) ne doit pas être inclus dans la liste des perturbateurs endocriniens

A French ministerial decree planning to include cholecalciferol, i.e. vitamin D3 (VD3), in the endocrine disruptors (ED) list has generated a lot of concerns in French physicians and scientists. The aim of the present article was to discuss the scientific rationale that may support or not this decision, which seems to be due to the use of VD3 overdose as a rodenticide in some European countries. First, it is noticeable that cholecalciferol is not an "exogenous substance", a term used in all the definitions of ED, as it is largely synthesized in the skin after UVB rays exposure. Second, we did not find any published article that may support the inclusion of VD3 in the ED list. The request "vitamin D AND endocrine disruptor" reported 33 references in the PubMed database on March, 10, 2022, most of them discussing disturbances of vitamin D metabolism by EDs. Third, a large amount of studies conclude that VD3 has or may have beneficial effects on many functions that are known to be altered by EDs. In addition, we warn that learning that VD3 could be legally considered as a PE may cause the general public to mistrust vitamin D supplementation, which is not desirable in terms of public health as it may increase the already too high prevalence of vitamin D deficient individuals. We consider the aberrant decision of including cholecalciferol in the ED list should be rapidly invalidated before being effective in France and possibly disseminated in the European Union.

Un projet d'arrêté ministériel inscrivant le cholécalciférol, c'est-à-dire la vitamine D3 (VD3), dans la liste des perturbateurs endocriniens (PE) est à l'origine de débats en France. L'objectif de notre article était de préciser les arguments scientifiques pour et contre l'inscription de la VD3 dans la liste des PE, qui semble être initialement due à son utilisation à très forte dose comme raticide/rodenticide dans certains pays. Premièrement, le cholécalciférol ne peut être défini comme une substance exogène, terme utilisé dans les différentes définitions des PE, car il est largement synthétisé dans la peau suite à l'exposition aux UVB. Deuxièmement, il n'existe aucune publication dans la base de données PubMed en faveur d'une inscription de la VD3 dans la liste des PE. La requête « vitamin D AND endocrine disruptor ¼ retrouvait 33 références au 10 mars 2022, la plupart évoquant des perturbations du métabolisme de la vitamine D par les PE. Troisièmement, un grand nombre d'études concluent, au contraire, que la VD3 a des effets bénéfiques sur de nombreuses fonctions altérées par les PE. Plus largement, nous alertons sur le fait qu'apprendre que la VD3 pourrait être règlementairement considérée comme un PE pourrait occasionner, auprès du grand public, une défiance vis-à-vis de la supplémentation en vitamine D, ce qui n'est pas souhaitable en termes de santé publique car de nature à aggraver la prévalence déjà trop élevée des individus carencés en vitamine D. Il est encore temps d'éviter cette décision aberrante et non fondée.

Whole Exome/Genome Sequencing Joint Analysis of a Family with Oligogenic Familial Hypercholesterolemia.

Autosomal Dominant Hypercholesterolemia (ADH) is a genetic disorder caused by pathogenic variants in LDLR, APOB, PCSK9 and APOE genes. We sought to identify new candidate genes responsible for the ADH phenotype in patients without pathogenic variants in the known ADH-causing genes by focusing on a French family with affected and non-affected members who presented a high ADH polygenic risk score (wPRS). Linkage analysis, whole exome and whole genome sequencing resulted in the identification of variants p.(Pro398Ala) in CYP7A1, p.(Val1382Phe) in LRP6 and p.(Ser202His) in LDLRAP1. A total of 6 other variants were identified in 6 of 160 unrelated ADH probands: p.(Ala13Val) and p.(Aps347Asn) in CYP7A1; p.(Tyr972Cys), p.(Thr1479Ile) and p.(Ser1612Phe) in LRP6; and p.(Ser202LeufsTer19) in LDLRAP1. All six probands presented a moderate wPRS. Serum analyses of carriers of the p.(Pro398Ala) variant in CYP7A1 showed no differences in the synthesis of bile acids compared to the serums of non-carriers. Functional studies of the four LRP6 mutants in HEK293T cells resulted in contradictory results excluding a major effect of each variant alone. Within the family, none of the heterozygous for only the LDLRAP1 p.(Ser202His) variant presented ADH. Altogether, each variant individually does not result in elevated LDL-C; however, the oligogenic combination of two or three variants reveals the ADH phenotype.

Dietary cholesterol: from physiology to cardiovascular risk.

Dietary cholesterol comes exclusively from animal sources, thus it is naturally present in our diet and tissues. It is an important component of cell membranes and a precursor of bile acids, steroid hormones and vitamin D. Contrary to phytosterols (originated from plants), cholesterol is synthesised in the human body in order to maintain a stable pool when dietary intake is low. Given the necessity for cholesterol, very effective intestinal uptake mechanisms and enterohepatic bile acid and cholesterol reabsorption cycles exist; conversely, phytosterols are poorly absorbed and, indeed, rapidly excreted. Dietary cholesterol content does not significantly influence plasma cholesterol values, which are regulated by different genetic and nutritional factors that influence cholesterol absorption or synthesis. Some subjects are hyper-absorbers and others are hyper-responders, which implies new therapeutic issues. Epidemiological data do not support a link between dietary cholesterol and CVD. Recent biological data concerning the effect of dietary cholesterol on LDL receptor-related protein may explain the complexity of the effect of cholesterol on CVD risk.

Realistic approach of pesticide residues and French consumer exposure within fruit & vegetable intake.

The increase of fruit and vegetable (F&V) intake contributes to the prevention of chronic diseases, but could also significantly increase pesticide exposure and may thus be of health concern. Following a previous pesticide exposure assessment study, the present study was carried out to determine actual levels of pesticides within 400 g of F&V intake and to evaluate consumer risk. Forty-three Active Substances (AS) exceeding 10 % of the Acceptable Daily Intake (ADI) in balanced menus established for our previous theoretical study were considered. Fifty-six pooled food samples were analyzed: 28 fruit samples and 28 vegetable samples. Pesticide values were compared to Maximum Residue Levels (MRL) and to the "toxicological credit" derived from ADI. It was observed that 23 out of the 43 retained AS were never detected, 5 were detected both in F&V samples, 12 only in fruits and 3 only in vegetables. The most frequently detected AS were carbendazim, iprodione and dithiocarbamates. When detected, AS were more frequently found in fruit samples (74 %) than in vegetable samples (26 %). A maximum of 3 AS were detected at once in a given sample. Overall, we observed 8 and 14 overruns of the MRL in 1204 measures in pooled vegetable and fruit samples, respectively (0.7 % and 1.2 % of cases, respectively). Chronic exposure for adults was the highest for dithiocarbamates but did not exceed 23.7 % of the ADI in F&V. It was concluded that raising both F&V consumption up to 400 g/day (~5 F&V/day) according to recommendations of the national health and nutrition plan, does not induce pesticide overexposure and should not represent a risk for the consumer.

[Meat and human health: excess and errors]. / Viande et santé humaine: excès et défauts.

Many studies have examined the influence of meat consumption on human health. Meat eaters have a higher body mass index and more weight gain than vegetarians. The risk of type 2 diabetes has also been linked to high meat consumption. However, the statistical correlations with these metabolic disorders are weak. There is inconsistent evidence of a higher cardiovascular risk. A link between high meat consumption and cancer, particularly colorectal cancer, has been observed in nearly all epidemiological studies. Some studies have also shown a link with breast, prostate and lung cancer. The mode of cooking could be partly En 2 responsible for this effect, due for example to heterocyclic aromatic amines production euro during grilling and intensive cooking. Advice is given.

The ALGOVUE Clinical Trial: Effects of the Daily Consumption of Eggs Enriched with Lutein and Docosahexaenoic Acid on Plasma Composition and Macular Pigment Optical Density.

BACKGROUND: Carotenoids and docosahexaenoic acid (DHA) were identified as essential components for eye health and are both naturally present in eggs. OBJECTIVE: We aimed to evaluate the effect of the daily consumption of two eggs enriched with lutein/zeaxanthin and DHA on macular pigment optical density (MPOD) and on circulating xanthophyll and fatty acid concentrations in healthy participants. METHODS: Ninety-nine healthy volunteers consumed either two standard eggs or two enriched eggs per day for 4 months. MPOD was measured at baseline (V0) and at follow-up (V4) using a modified confocal scanning laser ophthalmoscope (primary outcome). Blood samples were collected to determine total plasma and lipoprotein fatty acids and lutein/zeaxanthin compositions at V0 and V4 (secondary outcomes). RESULTS: A slight but significant increase in MPOD was observed for all study participants consuming two eggs per day for 4 months at all eccentricities (0.5°, 1°, 2°, and 4°). Plasma and lipoprotein lutein, zeaxanthin, and DHA concentrations significantly increased in both groups but were greater in the enriched group (for the enriched group (V0 vs. V4): lutein, 167 vs. 369 ng/mL; zeaxanthin, 17.7 vs. 29.2 ng/mL; DHA, 1.89 vs. 2.56% of total fatty acids). Interestingly, lutein from high-density lipoprotein (HDL) was strongly correlated with MPOD at 0.5 and 1° eccentricities (rho = 0.385, p = 0.008, and rho = 0.461, p = 0.001, respectively). CONCLUSIONS: MPOD was slightly increased in both groups. Lutein, zeaxanthin, and DHA plasma concentrations were strongly enhanced in the enriched group compared with the standard group. A significant correlation was found between MPOD level and lutein concentration in HDL.

A phase 1 trial of lipid-encapsulated mRNA encoding a monoclonal antibody with neutralizing activity against Chikungunya virus.

Chikungunya virus (CHIKV) infection causes acute disease characterized by fever, rash and arthralgia, which progresses to severe and chronic arthritis in up to 50% of patients. Moreover, CHIKV infection can be fatal in infants or immunocompromised individuals and has no approved therapy or prevention. This phase 1, first-in-human, randomized, placebo-controlled, proof-of-concept trial conducted from January 2019 to June 2020 evaluated the safety and pharmacology of mRNA-1944, a lipid nanoparticle-encapsulated messenger RNA encoding the heavy and light chains of a CHIKV-specific monoclonal neutralizing antibody, CHKV-24 ( NCT03829384 ). The primary outcome was to evaluate the safety and tolerability of escalating doses of mRNA-1944 administered via intravenous infusion in healthy participants aged 18-50 years. The secondary objectives included determination of the pharmacokinetics of mRNA encoding for CHKV-24 immunoglobulin heavy and light chains and ionizable amino lipid component and the pharmacodynamics of mRNA-1944 as assessed by serum concentrations of mRNA encoding for CHKV-24 immunoglobulin G (IgG), plasma concentrations of ionizable amino lipid and serum concentrations of CHKV-24 IgG. Here we report the results of a prespecified interim analysis of 38 healthy participants who received intravenous single doses of mRNA-1944 or placebo at 0.1, 0.3 and 0.6 mg kg-1, or two weekly doses at 0.3 mg kg-1. At 12, 24 and 48 h after single infusions, dose-dependent levels of CHKV-24 IgG with neutralizing activity were observed at titers predicted to be therapeutically relevant concentrations (≥1 µg ml-1) across doses that persisted for ≥16 weeks at 0.3 and 0.6 mg kg-1 (mean t1/2 approximately 69 d). A second 0.3 mg kg-1 dose 1 week after the first increased CHKV-24 IgG levels 1.8-fold. Adverse effects were mild to moderate in severity, did not worsen with a second mRNA-1944 dose and none were serious. To our knowledge, mRNA-1944 is the first mRNA-encoded monoclonal antibody showing in vivo expression and detectable ex vivo neutralizing activity in a clinical trial and may offer a treatment option for CHIKV infection. Further evaluation of the potential therapeutic use of mRNA-1944 in clinical trials for the treatment of CHIKV infection is warranted.

Pesticide residues intake of French adults under increased consumption of fresh fruits and vegetables--a theoretical study.

The increase of fresh vegetable and fruit (FVF) intake could contribute to the prevention of obesity and several major pathologies and thus represents a major public health goal in industrial countries. Nutritional recommendations for increased consumption of FVF could lead to ingestion of unwanted amounts of pesticides. This study was undertaken to evaluate theoretical exposure of French adults to pesticide residues under increasing amounts of FVF intake. Balanced menus with 200 - 400 - 600 - 800 and 1200 g FVF/day were established. Amounts of active substances brought by every FVF vector, at the maximum residue level (MRL) were summed up to determine the intake for each active substance. Values were compared to the Acceptable Daily Intake (ADI) to point out any potential over exposure. A maximalistic approach was adopted and no reducing factor due to processing was taken into account. It was found that under minimal recommended consumption of fruit and vegetables (400 g/d), no active substance reached the ADI, but 18 vs 144 were over 10% of the ADI. Raising FVF to 600 g/d increased the number of active substances over 10 % of the ADI to 24, but again in no case was the ADI exceeded. Doubling the intake to 800 g/d gives values over the ADI for 2 active substances only (cyhexatin and thirame). It was concluded that the increase in fruit and vegetables up to 800 g per day should not expose adults over the ADIs for a majority of authorized pesticides. In this regard, residues levels of ten active substances in fruit and vegetables should deserve particular attention.