Moving beyond metrics: Capturing the clinical context behind antibiotic prescriptions in French broiler production

International audienceSignificant reductions in antimicrobial use (AMU) in food production animals have been observed over the last10 years across Europe. We sought to understand recent changes in AMU by characterising antibiotic prescribingpatterns in poultry production in the context of associated clinical information. We analysed trends in AMU forconventional broiler chicken production in France based on a dataset of 193,526 sales for 33,831 flocks on 2120farms for 2015–2023, including 21,218 antibiotic prescriptions. We found the percentage of flocks prescribedantibiotics dropped from 65 % in 2013 to 20 % in 2023, plateauing in 2020–2023 (oscillating between 13 % and23 %), and observed a reduction in the use of critical antibiotics. A multiple correspondence analysis and hierarchicalclustering on principal components of 1112 antibiotic prescriptions and associated clinical data for2021–2022 produced 1940 prescription events, grouped in five clusters of antibiotic prescribing patterns, eachcharacterised by a combination of clinical indicators related to age at treatment, lesions, syndromes, diagnoses,and isolated bacteria. Two main clusters were associated with bacterial diagnoses, suggesting that use of antibioticsin these clusters was necessary to manage disease. Two clusters were identified as potential targets forfurther interventions to improve antimicrobial stewardship, focusing on underlying factors driving AMU ratherthan outright reductions. Our findings raise questions about the sustainability of further reductions in AMU andtheir implications for animal health and welfare. This calls for a shift to a more sustainable approach to monitoringantimicrobial stewardship, using integrated indicators which consider AMU within its broader context

Induction of human cytochrome P450 enzyme activities by metabolism disrupting chemicals in the hepatic cell line HepaRG

International audienceMetabolism disrupting chemicals (MDCs) are a class of endocrine disrupting substances that promote metabolic changes leading to metabolic disorders in humans. Central to assessing their adverse effects is the need to better understand their modes of action (MoA). Cytochrome P450 (CYP) enzymes play a major role in xenobiotic metabolism, but also catalyse many endogenous metabolic reactions. Therefore, modulation of CYP functionality may impact homeostasis, contributing to adverse outcomes. At the functional level, alteration of the activity of human CYPs J o u r n a l P r e -p r o o f by MDCs largely remains unexplored. In this study we investigated the capability of six candidate MDCs, bisphenol A (BPA), perfluorooctanoic acid (PFOA), tributyltin (TBT), dichlorodiphenyldichloroethylene (p,p'-DDE), triclosan (TCS) and triphenylphosphate (TPP) to induce CYP1A2, CYP2B6 and CYP3A4 activities in the human hepatic HepaRG cell line. The CYP induction test method previously validated for pharmaceuticals was optimised and selected MDCs were tested in the context of the European Horizon 2020 GOLIATH project. Induction was revealed using a cocktail of CYP-selective probe substrates, followed by probe metabolite quantification by mass spectrometry. All MDCs except TCS induced CYP activities. PFOA, TBT, p,p'-DDE and TPP induced CYP1A2, TPP being the most potent inducer. BPA, PFOA, TBT and TPP induced CYP2B6, PFOA being the most potent inducer. BPA, PFOA, TBT, p,p'-DDE and TPP all induced CYP3A4, p,p'-DDE and BPA being the most potent inducers. These results highlight the capability of candidate MDCs to induce key CYP activities in a human hepatic relevant model, paving the way for a better understanding of MDCs mechanisms of action

Seroprevalence of West Nile, Usutu and tick-borne encephalitis viruses in equids from south-western France in 2023

International audienceThe circulation of West Nile virus (WNV), Usutu virus (USUV), and tick-borne encephalitis virus (TBEV) was investigated in south-western France during the first six months of 2023, following the emergence of WNV in equids in Gironde, a département in south-western France, in 2022. Blood samples were collected from 494 horses located in the Gironde département and divided into three zones: the Confluence zone, the Intermediate zone and the Arcachon Basin. Samples were tested for WNV-, USUV- and TBEV-specific antibodies. An overall seroprevalence of 14% (95% CI [11–18%]) for orthoflavivirus antibodies was detected in Gironde. The highest seroprevalence rates for WNV and USUV were observed in the Confluence Zone (9%, 95% CI [6–13%] and 5%, 95% CI [3–8%], respectively), where the type of housing (animals kept in pasture only) and proximity to a special bird protection area were identified as risk factors for WNV seropositivity. This study presents the first seroprevalence investigation of WNV, USUV and TBEV infections in equids located on the Atlantic coast of France and demonstrates intense circulation of WNV in this region, as well as evidence of equine USUV-specific infection

Low Mutation Rate and Atypical Mutation Spectrum in Prasinoderma coloniale : Insights From an Early Diverging Green Lineage

International audienceMutations are the ultimate source of genetic diversity on which natural selection and genetic drift act, playing a crucial role in evolution and long-term adaptation. At the molecular level, the spontaneous mutation rate (µ), defined as the number of mutations per base per generation, thus determines the adaptive potential of a species. Through a mutation accumulation experiment, we estimate the mutation rate and spectrum in Prasinoderma coloniale, a phytoplankton species from an early-branching lineage within the Archaeplastida, characterized by an unusually high genomic guanine-cytosine (GC) content (69.8%). We find that P. coloniale has a very low total mutation rate of µ = 2.00 × 10−10. The insertion–deletion mutation rate is almost 5 times lesser than the single nucleotide mutation rate with µID = 3.40 × 10−11 and µSNM = 1.62 × 10−10. Prasinoderma coloniale also exhibits an atypical mutational spectrum: While essentially all other eukaryotes show a bias toward GC to AT mutations, no evidence of this AT-bias is observed in P. coloniale. Since cytosine methylation is known to be mutagenic, we hypothesized that this may result from an absence of C-methylation. Surprisingly, we found high levels of C-methylation (14% in 5mC, 25% in 5mCG contexts). Methylated cytosines did not show increased mutation rates compared with unmethylated ones, not supporting the prevailing notion that C-methylation universally leads to higher mutation rates. Overall, P. coloniale combines a GC-rich genome with a low mutation rate and original mutation spectrum, suggesting the almost universal AT-bias may not have been present in the ancestor of the green lineage

Relationship between non-typhoidal Salmonella dose and food poisoning in humans: A systematic review

International audienceFood safety is a major public health concern. The zoonotic pathogen non-typhoidal Salmonella, responsible for salmonellosis, is a leading cause of bacterial food poisoning globally, making its detection and control essential. Understanding the infectious dose of Salmonella is crucial for identifying appropriate risk management strategies; however, significant uncertainties remain, warranting a systematic review. Following PRISMA guidelines, we conducted a comprehensive search across multiple databases (Web of Science, PubMed, and CAB Abstracts) to identify relevant studies examining the relationship between Salmonella dose and foodborne illness in humans. Four main types of studies were identified: experimental trials, case reports, case series, and mathematical modelling. An analysis of these studies revealed their respective strengths and limitations. The data showed considerable variability, with the dose required to cause illness depending on factors such as Salmonella serovar, food type, and the health status of the exposed population. A key challenge identified was the lack of sufficient data on collective food poisoning incidents, which complicates the development of more reliable dose-response models. Despite these limitations, this review underscores the importance of targeted food safety interventions and risk assessments tailored to specific food products and population groups. The findings provide a foundation for enhanced food safety measures and support ongoing efforts to protect public health from foodborne illnesses

RNA-Seq data provide new insights into the molecular regulation of breast muscle glycogen reserves, a key factor in muscle function and meat quality in chickens

International audienceResearch is needed to better understand the molecular mechanisms that influence muscle glycogen reserves in chickens due to their critical influence on muscle function and meat quality. In this study, breast muscle RNA sequencing data (RNA-Seq) were used to compare the transcriptomic profile of two original chicken lines divergently selected for breast muscle ultimate pH, which is a proxy for glycogen reserves. Weighted gene co-expression network analysis (WGCNA) of muscle and jejunum RNA-Seq data was also performed to highlight biological processes specifically involved in the gut-muscle dialogue that may contribute to the divergence in glycogen reserves between the two lines. Breast muscle RNA-Seq analysis of 4-week-old birds from the 15th generation of selection, in which glycogen reserves in the pHu-line were twice as high as that in the pHu+ line, revealed 2676 differentially expressed genes (Padj <= 0.05). Functional analysis of the genes overexpressed in the pHu-line highlighted enrichment in processes related to energy production from a wide range of substrates and pathways, as well as to processes involved in development of blood and lymph tissue. Diverse processes were enriched for genes overexpressed in the pHu+ line: muscle development and remodeling, lipid metabolism, immune response and inflammation, which suggested molecular changes much larger than those for carbohydrate metabolism. WGCNA revealed 64 modules of co-expressed genes. One, which contained 30 % genes expressed in the jejunum and 70 % genes expressed in the muscle, was correlated (P <= 0.05) with muscle glycogen reserves and several indicators of intestinal anatomy and health. Functional analysis of it showed an enrichment of processes related to transmission of nerve information and tissue oxygenation that seem to be involved in the gut-muscle dialogue that mediates establishment of breast muscle glycogen reserves. Finally, the study found that transcriptional regulations observed in muscle of the pHu+ line were similar to those in muscle afflicted with "wooden breast", which highlighted a dysfunction of mitochondrial metabolism and suggested several potential gene markers for both conditions

In Vitro Dermal Absorption of Key Colour Developers in Thermal Paper: A Focus on Bisphenol A, Bisphenol S and Pergafast 201

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Humans as a potential reservoir for the emerging ST301 Shiga toxin-producing Escherichia coli clones of serotype O80:H2?

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Health and environmental benefits of the design of a novel hybrid food mixing meat and mushroom

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Palmitate potentiates the SMAD3-PAI-1 pathway by reducing nuclear GDF15 levels

International audienceNuclear growth differentiation factor 15 (GDF15) reduces the binding of the mothers' against decapentaplegic homolog (SMAD) complex to its DNA-binding elements. However, the stimuli that control this process are unknown. Here, we examined whether saturated fatty acids (FA), particularly palmitate, regulate nuclear GDF15 levels and the activation of the SMAD3 pathway in human skeletal myotubes and mouse skeletal muscle, where most insulin-stimulated glucose use occurs in the whole organism. Human LHCN-M2 myotubes and skeletal muscle from wild-type and Gdf15 -/-mice fed a standard (STD) or a high-fat (HFD) diet were subjected to a series of studies to investigate the involvement of lipids in nuclear GDF15 levels and the activation of the SMAD3 pathway. The saturated FA palmitate, but not the monounsaturated FA oleate, increased the expression of GDF15 in human myotubes and, unexpectedly, decreased its nuclear levels. This reduction was prevented by the nuclear export inhibitor leptomycin B. The decrease in nuclear GDF15 levels caused by palmitate was accompanied by increases in SMAD3 protein levels and in the expression of its target gene SERPINE1, which encodes plasminogen activator inhibitor 1 (PAI-1). HFD-fed Gdf15 -/-mice displayed aggravated glucose intolerance compared to HFD-fed WT mice, with increased levels of SMAD3 and PAI-1 in the skeletal muscle. The increased PAI-1 levels in the skeletal muscle of HFD-fed Gdf15 -/-mice were accompanied by a reduction in one of its targets, hepatocyte growth factor (HGF)α, a cytokine involved in glucose metabolism. Interestingly, PAI-1 acts as a ligand of signal transducer and activator of transcription 3 (STAT3) and the phosphorylation of this transcription factor was exacerbated in HFD-fed Gdf15 -/-mice compared to HFD-fed WT mice. At the same time, the protein levels of insulin receptor substrate 1 (IRS-1) were reduced. These findings uncover a potential novel mechanism through which palmitate induces the SMAD3-PAI-1 pathway to promote insulin resistance in skeletal muscle by reducing nuclear GDF15 levels