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Background: Low blood status in several nutritional compounds, including long-chain omega-3 fatty acids (LC n-3 PUFA), carotenoids, and vitamin D, have been associated with a higher risk to develop dementia. Nutritional deficiencies may potentiate each other regarding dementia risk; yet the association of multiple nutritional deficiencies with dementia has been little explored. Objective: To develop an index of micronutritional biological status (MNBS) for the screening of multi-micronutritional deficiencies associated with the risk of dementia in a prospective population-based cohort of older persons. Methods: We included participants from the Bordeaux Three-City study, who were free of dementia at baseline, had blood measurements of LC n-3 PUFA, carotenoids, and 25(OH)D, and who were followed for up to 18 years for dementia. We used penalized splines in Cox models to model dose-response relationships of each nutritional component with the risk of dementia and construct a risk index. Results: 629 participants with an average age of 73.1 years were included in the study. Each increase of 1 SD of the MNBS index was associated with a 46%higher risk of dementia (HR = 1.46, 95%CI 1.23; 1.73). Participants with highest index ([mean+1SD; max]) had a 4-fold increased risk of dementia compared with participants with a low index ([min; mean-1SD]) (HR = 4.17, 95%CI 2.30; 7.57). Conclusion: This index of assessment of micronutritional biological status is a practical tool that may help identify populations with inadequate nutritional status, screen eligible individuals for nutritional prevention in primary care, or for supplementation in preventive trials of dementia.

Shigella is one of the commonest causes of diarrhoea worldwide and a major public health problem. Shigella serotyping is based on a standardized scheme that splits Shigella strains into four serogroups and 60 serotypes on the basis of biochemical tests and O-antigen structures. This conventional serotyping method is laborious, time-consuming, impossible to automate, and requires a high level of expertise. Whole-genome sequencing (WGS) is becoming more affordable and is now used for routine surveillance, opening up possibilities for the development of much-needed accurate rapid typing methods. Here, we describe ShigaPass, a new in silico tool for predicting Shigella serotypes from WGS assemblies on the basis of rfb gene cluster DNA sequences, phage and plasmid-encoded O-antigen modification genes, seven housekeeping genes (EnteroBase’s MLST scheme), fliC alleles and clustered regularly interspaced short palindromic repeats (CRISPR) spacers. Using 4879 genomes, including 4716 reference strains and clinical isolates of Shigella characterized with a panel of biochemical tests and serotyped by slide agglutination, we show here that ShigaPass outperforms all existing in silico tools, particularly for the identification of Shigella boydii and Shigella dysenteriae serotypes, with a correct serotype assignment rate of 98.5 % and a sensitivity rate (i.e. ability to make any prediction) of 100 %.

Raw reads of the 34 genomes of S. Bovismorbificans and 12 genomes of S. Typhimurium from human and food origin in this study were submitted to the European Nucleotide Archive under project numbers PRJEB41645 and PRJEB49565.; International audience; The French National Reference Centre for Escherichia coli, Shigella and Salmonella (FNRC-ESS) detected two human clusters of 33 cases (median age: 10 years; 17 females) infected by Salmonella enterica serotype Bovismorbificans, ST142, HC5_243255 (EnteroBase HierCC‑cgMLST scheme) in September-November 2020 and of 11 cases (median age: 11 years; seven males) infected by S. enterica serotype 4,12:i:-, ST34, HC5_198125 in October-December 2020. Epidemiological investigations conducted by Santé publique France linked these outbreaks to the consumption of dried pork sausages from the same manufacturer. S. Bovismorbificans and S. 4,12:i:- were isolated by the National Reference Laboratory from different food samples, but both strains were identified in a single food sample only by qPCR. Three recalls and withdrawals of dried pork products were issued by the French general directorate of food of the French ministry for agriculture and food in November 2020, affecting eight supermarket chains. A notification on the European Rapid Alert System for Food and Feed and a European urgent enquiry on the Epidemic Intelligence Information System for Food and Waterborne Diseases and Zoonoses (EPIS-FWD) were launched. No cases were reported outside France. Outbreaks caused by multiple serotypes of Salmonella may go undetected by protocols in standard procedures in microbiology laboratories.

Nutrition is a complex exposure (i.e., the food exposome) that influences brain function and health through multiple pathways. We review recent epidemiological studies that have improved the characterization of the food exposome and brain health in humans and have revealed promising nutrition-based strategies to prevent cognitive aging.A selection of epidemiological research from the past 18 months of both observational and clinical studies is presented, with a focus on novel findings, including novel nutrient and diet patterns, diet-related approaches to rescue brain energetics defects in aging, and biomarker-based studies to decipher specific neurobiological pathways of nutrition and brain health.Although healthy diets such as the Mediterranean diet promote brain health throughout life, specific diets, such as the Mediterranean-Dietary Approaches to Stop Hypertension Intervention for Neurodegenerative Delay diet, or specific nutrients (LC n-3 polyunsaturated fatty acids, carotenoids, vitamin D, B vitamins, polyphenols) alone or in combination, may prevent cognitive aging. Diet management approaches to rescue brain energetics defects such as the Modified Mediterranean-ketogenic diet may be promising to prevent neurodegenerative diseases. Expanding research also suggests that promotion of a healthy gut microbiome through prebiotic foods may preserve the diet-gut-brain axis with aging. Future studies should explore more individualized preventive approaches through a 'precision nutrition' framework.

The role of nutrition has been investigated for decades under the assumption of one-size-fits-all. Yet there is heterogeneity in metabolic and neurobiological responses to diet. Thus a more personalized approach may better fit biological reality and have increased efficacy to prevent dementia. Personalized nutrition builds on the food exposome, defined as the history of diet-related exposures over the lifetime, and on its interactions with the genome and other biological characteristics (eg, metabolism, the microbiome) to shape health. We review current advances of personalized nutrition in dementia research. We discuss key questions, success milestones, and future roadmap from observational epidemiology to clinical studies through basic science. A personalized nutrition approach based on the best prescription for the most appropriate target population in the most relevant time-window has the potential to strengthen dementia-prevention efforts.

The gut microbiome is involved in nutrient metabolism and produces metabolites that, via the gut–brain axis, signal to the brain and influence cognition. Human studies have so far had limited success in identifying early metabolic alterations linked to cognitive aging, likely due to limitations in metabolite coverage or follow-ups. Older persons from the Three-City population-based cohort who had not been diagnosed with dementia at the time of blood sampling were included, and repeated measures of cognition over 12 subsequent years were collected. Using a targeted metabolomics platform, we identified 72 circulating gut-derived metabolites in a case–control study on cognitive decline, nested within the cohort (discovery n = 418; validation n = 420). Higher serum levels of propionic acid, a short-chain fatty acid, were associated with increased odds of cognitive decline (OR for 1 SD = 1.40 (95% CI 1.11, 1.75) for discovery and 1.26 (1.02, 1.55) for validation). Additional analyses suggested mediation by hypercholesterolemia and diabetes. Propionic acid strongly correlated with blood glucose (r = 0.79) and with intakes of meat and cheese (r > 0.15), but not fiber (r = 0.04), suggesting a minor role of prebiotic foods per se, but a possible link to processed foods, in which propionic acid is a common preservative. The adverse impact of propionic acid on metabolism and cognition deserves further investigation.

International audience; Metabolic syndrome (MetS) is a complex condition encompassing a constellation of cardiometabolic abnormalities. Oxylipins are a superfamily of lipid mediators regulating many cardiometabolic functions. Plasma oxylipin signature could provide a new clinical tool to enhance the phenotyping of MetS pathophysiology. A high-throughput validated mass spectrometry method, allowing for the quantitative profiling of over 130 oxylipins, was applied to identify and validate the oxylipin signature of MetS in two independent nested case/control studies involving 476 participants. We identified an oxylipin signature of MetS (coined OxyScore), including 23 oxylipins and having high performances in classification and replicability (cross-validated AUCROC of 89%, 95% CI: 85–93% and 78%, 95% CI: 72–85% in the Discovery and Replication studies, respectively). Correlation analysis and comparison with a classification model incorporating the MetS criteria showed that the oxylipin signature brings consistent and complementary information to the clinical criteria. Being linked with the regulation of various biological processes, the candidate oxylipins provide an integrative phenotyping of MetS regarding the activation and/or negative feedback regulation of crucial molecular pathways. This may help identify patients at higher risk of cardiometabolic diseases. The oxylipin signature of patients with metabolic syndrome enhances MetS phenotyping and may ultimately help to better stratify the risk of cardiometabolic diseases.

Background Vitamin D is critical to brain health and a promising candidate to prevent cognitive decline and onset of Alzheimer disease (AD), although the underlying brain mechanisms are unclear. Objectives This study aimed to determine the association between vitamin D intake and brain cortical thickness in older adults. Methods This was a cross-sectional investigation of 263 cognitively unimpaired participants, aged 65 y and older, participating in the MIND (Mediterranean-DASH Intervention for Neurodegenerative Delay) trial (an ongoing study testing the effects of a 3-y diet intervention on cognitive decline). Vitamin D intake, from diet and supplements, was ascertained from an FFQ. Linear regression analysis, adjusted for age, sex, race, education, income, cognitive and physical activities, and cardiovascular disease risk factors, was used to determine the association between vitamin D intake and cortical thickness of the whole brain, lobes, and AD signature. Results Total vitamin D intake was associated with cortical thickness of the temporal lobe and AD signature. Compared with individuals in the lowest quartile of total vitamin D intake [median: 140 international units (IU)/d], those in the highest quartile (median: 1439 IU/d) had a 0.038-mm (95% CI: 0.006, 0.069 mm) thicker temporal lobe and 0.041-mm (95% CI: 0.012, 0.070 mm) thicker AD signature. Most vitamin D intake was from supplements, and supplemental intake was also associated with cortical thickness. Compared with those who used no supplement, individuals taking 800-1000 IU/d and >1000 IU/d of supplemental vitamin D had a 0.039-mm (95% CI: 0.013, 0.066 mm) and 0.047-mm (95% CI: 0.013, 0.081 mm) thicker temporal lobe and a 0.037-mm (95% CI: 0.013, 0.061 mm) and 0.046-mm (95% CI: 0.015, 0.077 mm) thicker AD signature, respectively. Dietary vitamin D was not related to brain cortical thickness in our sample. Conclusions In cognitively unimpaired older adults, total and supplemental vitamin D intakes were associated with cortical thickness in regions vulnerable to AD.This trial was registered at clinicaltrials.gov as NCT02817074.

Background The COVID‐19 pandemic may induce post‐traumatic stress disorder (PTSD) symptoms among patients with cancer, who also face adaptations to their treatment. The authors assessed the occurrence of PTSD symptoms, investigated pandemic‐induced adjustments in medical oncology practice in patients with cancer, and explored risk factors for PTSD and the association between PTSD symptoms, insomnia, and quality of life (QoL). Methods This prospective French study was conducted in patients with solid/hematologic tumors who were receiving medical treatment in the day care departments of 2 cancer centers during the lockdown. Adjustments to medical oncology practice were collected from medical records. PTSD (measured using the Impact of Event Scale‐Revised), insomnia (measured using the Insomnia Severity Index), QoL (measured using the Functional Assessment of Cancer Therapy‐General instrument), and cognitive complaints (measured using the Functional Assessment of Cancer Therapy–Cognitive Function instrument) were collected through validated questionnaires. Results Clinical data and questionnaires were available for 734 and 576 patients, respectively. The median patient age was 64 years, and 69% of patients were women. Twenty‐one percent of patients had PTSD. Twenty‐seven percent (95% CI, 23%‐30%) had an adjustment in their medical oncology program, including adjournments (29%), treatment interruptions (16%), modified treatment plans (27%), or adapted monitoring (27%). Women and patients experiencing an adjustment in oncology practice had a higher odds of PTSD (odds ratio= 2.10 [95% CI, 1.07‐4.14] and 1.65 [95% CI, 1.03‐2.63]; P, Post‐traumatic stress disorder symptomatology occurred in 21% of patients with cancer during the first lockdown due to COVID‐19, was more frequent among women, and was associated with adjustment in medical oncology treatments. Caregivers should pay special attention to the psychological needs of patients with cancer to prevent or manage post‐traumatic stress disorder symptoms.

Shigella sonnei causes shigellosis, a severe gastrointestinal illness that is sexually transmissible among men who have sex with men (MSM). Multidrug resistance in S. sonnei is common including against World Health Organisation recommended treatment options, azithromycin, and ciprofloxacin. Recently, an MSM-associated outbreak of extended-spectrum β-lactamase producing, extensively drug resistant S. sonnei was reported in the United Kingdom. Here, we aimed to identify the genetic basis, evolutionary history, and international dissemination of the outbreak strain. Our genomic epidemiological analyses of 3,304 isolates from the United Kingdom, Australia, Belgium, France, and the United States of America revealed an internationally connected outbreak with a most recent common ancestor in 2018 carrying a low-fitness cost resistance plasmid, previously observed in travel associated sublineages of S. flexneri. Our results highlight the persistent threat of horizontally transmitted antimicrobial resistance and the value of continuing to work towards early and open international sharing of genomic surveillance data.

Background: Current standards for toxicity reporting do not fully capture the impact of adverse events (AEs) on patients’ quality of life (QoL). This study aimed to evaluate the association between toxicity and QoL by using toxicity scores that take into account CTCAE grade grouping and AE duration and cumulation. Methods: Analyses were performed on the AURELIA trial dataset, including 361 patients with platinum-resistant ovarian cancer treated with chemotherapy alone or with bevacizumab. Global and physical functioning QoL were issued from the EORTC QoL Questionnaire-Core 30 (QLQ-C30), collected at baseline and 8/9 and 16/18 weeks after treatment initiation. Four toxicity scores were computed: the total number of AEs, multiplied by their grade and not, and the cumulative duration of AEs, weighted by their grade and not. Each score included all AEs or only grade 3/4 nonlaboratory or treatment-related AEs. The relationship between toxicity scores and QoL was assessed through linear mixed regression. Results: We found that 171 (47.5%) and 43 (11.9%) patients experienced at least one grade 3 or 4 AE, respectively, whereas 113 (31.4%) experienced grade 2 AEs only. Physical QoL was negatively associated with all toxicity scores when computed with all grades of AEs (all PPConclusions: In this analysis of patients with platinum-resistant ovarian cancer, toxicity scores based on the cumulative number of AEs, modulated or not by grade, were more effective at predicting QoL changes than those based on AE duration. Toxicity impact on QoL was better reflected when grade 2 AEs were taken into account together with grade 3/4 AEs, whatever their treatment imputability, and when laboratory AEs were excluded.

Current evidence suggests that some isolated polyphenols (PP) may exert promising effects for the risk of depression in young adults, however studies among older adults remain limited. The aim of the current study was to examine the prospective association between patterns of PP intake and the risk of depressive symptomatology (DS) in older adults.The study sample was based on the Three-City (3C) Bordeaux cohort of adults aged 65 years and over and without DS at the time of recruitment. The intakes of PP, summarised into 21 PP classes, were determined using a 24-h recall combined with the Phenol-Explorer database. In addition, the patterns of PP intake were identified by a Principal Component Analysis (PCA). DS was evaluated using the Center for Epidemiologic Studies Depression Scale (CES-D) over a period of 15 years with a reassessment every 2-3 years. The incident DS was reported for CES-D score ≥16 and/or the use of antidepressant treatment. The association between the patterns of PP intake at baseline and the risk of DS was computed using multivariate random-effect logistic regression models.Among the 1074 participants (mean age 75.7 y, SD 4.8 y), 423 (39.4%) developed a DS during the follow-up. Distinct patterns of PP intake were identified, explaining up to 50% of the variance. The two first patterns, mainly driven by stilbenes and dihydroflavonols and by hydroxyicnnamic acid and alkylmethoxyphenols respectively, were not associated with the odds of DS. Furthermore, a higher score on the third pattern, mainly driven by monomeric flavanols and theaflavins, was associated with a significant 27% lower risk of DS over time (Odd Ratio = 0.73, 95% Confidence Interval [0.55; 0.97]).This prospective study suggested that a pattern high in monomeric flavanols and theaflavins intakes, mainly provided by tea, was associated with a reduced risk of DS in older adults. These results provide promising evidence on combined PP intakes that would require further confirmation in other samples.

International audience; Introduction: Diet and exercise influence the risk of cognitive decline (CD) and dementia through the food metabolome and exercise-triggered endogenous factors, which use the blood as a vehicle to communicate with the brain. These factors might act in concert with hippocampal neurogenesis (HN) to shape CD and dementia.Methods: Using an in vitro neurogenesis assay, we examined the effects of serum samples from a longitudinal cohort (n = 418) on proxy HN readouts and their association with future CD and dementia across a 12-year period.Results: Altered apoptosis and reduced hippocampal progenitor cell integrity were associated with exercise and diet and predicted subsequent CD and dementia. The effects of exercise and diet on CD specifically were mediated by apoptosis.Discussion: Diet and exercise might influence neurogenesis long before the onset of CD and dementia. Alterations in HN could signify the start of the pathological process and potentially represent biomarkers for CD and dementia.

ObjectiveTo use network science to model complex diet relationships a decade before onset of dementia in a large French cohort, the 3-City Bordeaux study.MethodsWe identified cases of dementia incident to the baseline food frequency questionnaire over 12 years of follow-up. For each case, we randomly selected 2 controls among individuals at risk at the age at case diagnosis and matched for age at diet assessment, sex, education, and season of the survey. We inferred food networks in both cases and controls using mutual information, a measure to detect nonlinear associations, and compared food consumption patterns between groups.ResultsIn the nested case-control study, the mean (SD) duration of follow-up and number of visits were 5.0 (2.5) vs 4.9 (2.6) years and 4.1 (1.0) vs 4.4 (0.9) for cases (n = 209) vs controls (n = 418), respectively. While there were few differences in simple, average food intakes, food networks differed substantially between cases and controls. The network in cases was focused and characterized by charcuterie as the main hub, with connections to foods typical of French southwestern diet and snack foods. In contrast, the network of controls included several disconnected subnetworks reflecting diverse and healthier food choices.ConclusionHow foods are consumed (and not only the quantity consumed) may be important for dementia prevention. Differences in predementia diet networks, suggesting worse eating habits toward charcuterie and snacking, were evident years before diagnosis in this cohort. Network methods, which are designed to model complex systems, may advance our understanding of risk factors for dementia.

BackgroundMetabolic syndrome (MetS) is a complex condition encompassing a constellation of cardiometabolic abnormalities. Integratively phenotyping the molecular pathways involved in MetS would help to deeply characterize its pathophysiology and to better stratify the risk of cardiometabolic diseases. Oxylipins are a superfamilly of lipid mediators regulating most biological processes involved in cardiometabolic health.MethodsA high-throughput validated mass spectrometry method allowing the quantitative profiling of over 130 oxylipins was applied to identify and validate the oxylipin signature of MetS in two independent case/control studies involving 476 participants.ResultsWe have uncovered and validated an oxylipin signature of MetS (coined OxyScore) including 23 oxylipins and having high performances of classification and replicability (cross-validated AUCROCof 89%, 95% CI: 85%-93% and 78%, 95% CI: 72%-85% in the Discovery and Replication studies, respectively). Correlation analysis and comparison with a classification model incorporating both the oxylipins and the MetS criteria showed that the oxylipin signature brings consistent and complementary information supporting its clinical utility. Moreover, the OxyScore provides a unique mechanistic signature of MetS regarding the activation and/or negative feedback regulation of crucial molecular pathways that may help identify patients at higher risk of cardiometabolic diseases.ConclusionOxylipin profiling identifies a mechanistic signature of metabolic syndrome that may help to enhance MetS phenotyping and ultimately to better predict the risk of cardiometabolic diseasesviaa better patient stratification.

BackgroundCancer patients may be particularly vulnerable to psychological consequences of the COVID-19 pandemic and successive lockdowns. We studied the prevalence and evolution of post-traumatic stress disorder (PTSD) symptoms in cancer patients during the pandemic waves, and investigated factors associated with high symptoms.MethodsCOVIPACT is a one-year longitudinal prospective study of French patients with solid/hematologic malignancy receiving treatment during the first nationwide lockdown. PTSD symptoms were measured every 3 months from April 2020 using the Impact of Event Scale-Revised. Patients also completed validated questionnaires on quality of life (QoL), cognitive complaints and insomnia, and a survey on their COVID-19 lockdown experience.ResultsLongitudinal analyses involved 386 patients with at least one PTSD assessment after baseline (median age 63, 76% female). Among them, 21.5% had moderate/severe PTSD symptoms during the first lockdown. The rate of patients reporting PTSD symptoms decreased at lockdown release (13.6%), increased again at second lockdown (23.2%), and slightly declined from the second release period (22.7%) to the third lockdown (17.5%). Patients were grouped into three trajectories of evolution. Most patients had stable low symptoms throughout the period, 6% had high baseline symptoms slowly decreasing over time, and 17.6% had moderate symptoms worsening during second lockdown. Female sex, feeling socially isolated, worrying about COVID-19 infection, and using psychotropic drugs were associated with PTSD symptoms. PTSD symptoms were associated with impaired QoL, sleep and cognition.ConclusionsAround a quarter of cancer patients presented high and persistent PTSD symptoms over the first year of the COVID-19 pandemic and may benefit from psychological support.

Background: Patients with cancer may be particularly vulnerable to psychological consequences of the COVID-19 pandemic. We studied the prevalence and evolution of posttraumatic stress symptoms (PTSS) in patients with cancer during the pandemic waves, and we investigated factors associated with high symptoms. Methods: COVIPACT is a 1-year longitudinal prospective study of French patients with solid/hematologic malignancies receiving treatment during the first nationwide lockdown. PTSS were measured every 3 months from April 2020 using the Impact of Event Scale–Revised. Patients also completed questionnaires on their quality of life, cognitive complaints, insomnia, and COVID-19 lockdown experience. Results: Longitudinal analyses involved 386 patients with at least one PTSS assessment after baseline (median age, 63 years; 76% female). Among them, 21.5% had moderate/severe PTSS during the first lockdown. The rate of patients reporting PTSS decreased at lockdown release (13.6%), increased again at second lockdown (23.2%), and slightly declined from the second release period (22.7%) to the third lockdown (17.5%). Patients were grouped into 3 trajectories of evolution. Most patients had stable low symptoms throughout the period, 6% had high baseline symptoms slowly decreasing over time, and 17.6% had moderate symptoms worsening during the second lockdown. Female sex, feeling socially isolated, worrying about COVID-19 infection, and using psychotropic drugs were associated with PTSS. PTSS were associated with impaired quality of life, sleep, and cognition. Conclusions: Approximately one-fourth of patients with cancer experienced high and persistent PTSS over the first year of the COVID-19 pandemic and may benefit from psychological support. ClinicalTrials.gov identifier: NCT04366154

We described and characterized Shiga-toxin-producing Escherichia coli (STEC) strains with high levels of resistance to azithromycin isolated in France between 2004 and 2020. Nine of 1,715 (0.52%) STEC strains were resistant to azithromycin, with an increase since 2017. One isolate carried a plasmid-borne mef(C)-mph(G) gene combination, described here for the first time for E. coli. Azithromycin resistance, although rare, needs consideration, as this treatment may be useful in cases of STEC infection.

The virulence-transmission trade-off predicts that parasite fitness peaks at intermediate virulence. However, whether this relationship is driven by the environment or genetically determined and if it depends on transmission opportunities remains unclear. We tackled these issues using inbred lines of the macro-parasitic spider-miteTetranychus urticae. When transmission was not possible during the infection period, we observed a hump-shaped relationship between virulence and parasite fitness, as predicted by theory. This was environmentally driven, as no genetic correlation between traits was detected. However, when transmission to uninfected hosts occurred during the infection period, virulence was positively, environmentally and genetically correlated with parasite fitness. Therefore, the virulence-transmission trade-off depends on within-host dynamics and on the timing of transmission, rather than on a genetic correlation. This fundamental correlation may thus be easier to manipulate than previously thought.

Environmental factors like diet have been linked to depression and/or relapse risk in later life. This could be partially driven by the food metabolome, which communicates with the brain via the circulatory system and interacts with hippocampal neurogenesis (HN), a form of brain plasticity implicated in depression aetiology. Despite the associations between HN, diet and depression, human data further substantiating this hypothesis are largely missing. Here, we used an in vitro model of HN to test the effects of serum samples from a longitudinal ageing cohort of 373 participants, with or without depressive symptomology. 1% participant serum was applied to human fetal hippocampal progenitor cells, and changes in HN markers were related to the occurrence of depressive symptoms across a 12-year period. Key nutritional, metabolomic and lipidomic biomarkers (extracted from participant plasma and serum) were subsequently tested for their ability to modulate HN. In our assay, we found that reduced cell death and increased neuronal differentiation were associated with later life depressive symptomatology. Additionally, we found impairments in neuronal cell morphology in cells treated with serum from participants experiencing recurrent depressive symptoms across the 12-year period. Interestingly, we found that increased neuronal differentiation was modulated by increased serum levels of metabolite butyrylcarnitine and decreased glycerophospholipid, PC35:1(16:0/19:1), levels – both of which are closely linked to diet – all in the context of depressive symptomology. These findings potentially suggest that diet and altered HN could subsequently shape the trajectory of late-life depressive symptomology.

Enterohemorrhagic Escherichia coli (EHEC) O80:H2, belonging to sequence type ST301, is among the main causes of hemolytic and uremic syndrome in Europe, a major concern in young children. Aside from the usual intimin and Shiga toxin virulence factors (VFs), this emerging serotype possesses a mosaic plasmid combining extra-intestinal VF- and antibiotic resistance-encoding genes. This hybrid pathotype can be involved in invasive infections, a rare occurrence in EHEC infections. Here, we aimed to optimize its detection, improve its clinical diagnosis, and identify its currently unknown reservoir. O80:H2 EHEC strains isolated in France between 2010 and 2018 were phenotypically and genetically analyzed and compared with non-O80 strains. The specificity and sensitivity of a PCR test and a culture medium designed, based on the molecular and phenotypic signatures of O80:H2 EHEC, were assessed on a collection of strains and stool samples. O80:H2 biotype analysis showed that none of the strains (n = 137) fermented melibiose versus 5% of non-O80 EHEC (n = 19/352). This loss of metabolic function is due to deletion of the entire melibiose operon associated with the insertion of a 70-pb sequence (70mel), a genetic scar shared by all ST301 strains. This metabolic hallmark was used to develop a real-time PCR test (100% sensitivity, 98.3% specificity) and a melibiose-based culture medium including antibiotics, characterized by 85% specificity and sensitivity for clinical specimens. These new tools may facilitate the diagnosis of this atypical clone, help the food industry to identify the reservoir and improve our epidemiological knowledge of this threatening and emerging clone.

The laboratory surveillance of bacillary dysentery is based on a standardised Shigella typing scheme that classifies Shigella strains into four serogroups and more than 50 serotypes on the basis of biochemical tests and lipopolysaccharide O-antigen serotyping. Real-time genomic surveillance of Shigella infections has been implemented in several countries, but without the use of a standardised typing scheme. We studied over 4,000 reference strains and clinical isolates of Shigella, covering all serotypes, with both the current serotyping scheme and the standardised EnteroBase core-genome multilocus sequence typing scheme (cgMLST). The Shigella genomes were grouped into eight phylogenetically distinct clusters, within the E. coli species. The cgMLST hierarchical clustering (HC) analysis at different levels of resolution (HC2000 to HC400) recognised the natural groupings for Shigella. By contrast, the serotyping scheme was affected by horizontal gene transfer, leading to a conflation of genetically unrelated Shigella strains and a separation of genetically related strains. The use of this cgMLST scheme will enhance the laboratory surveillance of Shigella infections.

Plant height was positively correlated with grain yield across a large set of 3-dwarf sorghum hybrids and production environments in north-eastern Australia. In industrialised countries, plant breeders tend to select for short plant stature in cereals like wheat, barley and rice, but also grain sorghum. This is mainly to prevent stalk lodging and to allow for machine harvesting. However, this counteracts an intrinsic positive relationship between plant height and yield potential often observed in cereals. We used data from multi-environment breeding trials comprising large sets of female sorghum lines from a range of pedigrees in hybrid combination with five different male testers. The hybrids were grown in 22 different rainfed environments in north-eastern Australia, which allowed us to thoroughly examine the relationship between plant height and yield across a range of productivity levels. Covariate analysis showed that in 38 out of the 90 tested relationships, grain yield was significantly (p

SCOPE: Diet is considered an important modulator of cognitive decline and dementia, but the available evidence is, however, still fragmented and often inconsistent.METHODS AND RESULTS: The article studies the long-term prospective Three-City Cohort, which consists of two separate nested case-control sample sets from different geographic regions (Bordeaux, n = 418; Dijon, n = 424). Cognitive decline is evaluated through five neuropsychological tests (Mini-Mental State Examination, Benton Visual Retention Test, Isaac's Set Test, Trail-Making Test part A, and Trail-Making Test part B). The food-related and microbiota-derived circulating metabolome is studied in participants free of dementia at baseline, by subjecting serum samples to large-scale quantitative metabolomics analysis. A protective association is found between metabolites derived from cocoa, coffee, mushrooms, red wine, the microbial metabolism of polyphenol-rich foods, and cognitive decline, as well as a negative association with metabolites related to unhealthy dietary components, such as artificial sweeteners and alcohol.CONCLUSION: These results provide insight into the early metabolic events that are associated with the later risk to develop cognitive decline within the crosstalk between diet, gut microbiota and the endogenous metabolism, which can help identify potential targets for preventive and therapeutic strategies to preserve cognitive health.

International audience; The age-associated reduction in the proliferation of neural stem cells (NSCs) has been associated with cognitive decline. Numerous factors have been shown to modulate this process, including dietary components. Frequent consumption of caffeine has been correlated with an increased risk of cognitive decline, but further evidence of a negative effect on hippocampal progenitor proliferation is limited to animal models. Here, we used a human hippocampal progenitor cell line to investigate the effects of caffeine on hippocampal progenitor integrity and proliferation specifically. The effects of five caffeine concentrations (0 mM = control, 0.1 mM ∼ 150 mg, 0.25 mM ∼ 400 mg, 0.5 mM ∼ 750 mg, and 1.0 mM ∼ 1500 mg) were measured following acute (1 day) and repeated (3 days) exposure. Immunocytochemistry was used to quantify hippocampal progenitor integrity (i.e., SOX2- and Nestin-positive cells), proliferation (i.e., Ki67-positive cells), cell count (i.e., DAPI-positive cells), and apoptosis (i.e., CC3-positive cells). We found that progenitor integrity was significantly reduced in supraphysiological caffeine conditions (i.e., 1.0 mM ∼ 1500 mg), but relative to the lowest caffeine condition (i.e., 0.1 mM ∼ 150 mg) only. Moreover, repeated exposure to supraphysiological caffeine concentrations (i.e., 1.0 mM ∼ 1500 mg) was found to affect proliferation, significantly reducing % Ki67-positive cells relative to control and lower caffeine dose conditions (i.e., 0.1 mM ∼ 150 mg and 0.25 mM ∼ 400 mg). Caffeine treatment did not influence apoptosis and there were no significant differences in any measure between lower doses of caffeine (i.e., 0.1 mM, 0.25 mM, 0.5 mM) - representative of daily human caffeine intake - and control conditions. Our study demonstrates that dietary components such as caffeine can influence NSC integrity and proliferation and may be indicative of a mechanism by which diet affects cognitive outcomes.

Background: Diet has been recognized as a modifiable risk factor for breast cancer. Highlighting predictive diet-related biomarkers would be of great public health relevance to identify at-risk subjects. The aim of this exploratory study was to select diet-related metabolites discriminating women at higher risk of breast cancer using untargeted metabolomics. Methods: Baseline plasma samples of 200 incident breast cancer cases and matched controls, from a nested case–control study within the Supplémentation en Vitamines et Minéraux Antioxydants (SU.VI.MAX) cohort, were analyzed by untargeted LC-MS. Diet-related metabolites were identified by partial correlation with dietary exposures, and best predictors of breast cancer risk were then selected by Elastic Net penalized regression. The selection stability was assessed using bootstrap resampling. Results: 595 ions were selected as candidate diet–related metabolites. Fourteen of them were selected by Elastic Net regression as breast cancer risk discriminant ions. A lower level of piperine (a compound from pepper) and higher levels of acetyltributylcitrate (an alternative plasticizer to phthalates), pregnene-triol sulfate (a steroid sulfate), and 2-amino-4-cyano butanoic acid (a metabolite linked to microbiota metabolism) were observed in plasma from women who subsequently developed breast cancer. This metabolomic signature was related to several dietary exposures such as a “Western” dietary pattern and higher alcohol and coffee intakes. Conclusions: Our study suggested a diet-related plasma metabolic signature involving exogenous, steroid metabolites, and microbiota-related compounds associated with long-term breast cancer risk that should be confirmed in large-scale independent studies. Impact: These results could help to identify healthy women at higher risk of breast cancer and improve the understanding of nutrition and health relationship.

Introduction Les patients traités pour un cancer étant à risque de développer des formes sévères de COVID-19, les autorités sanitaires ont émis des recommandations pour optimiser leur prise en charge dès le printemps 2020. En quelques semaines, la prise en charge des patients en onco-hématologie a été bouleversée pour limiter le risque de contamination par la COVID-19, entraînant possiblement une peur, une anxiété ou des troubles psychologiques tels qu’un stress post-traumatique. Dans ce contexte de pandémie, l’étude COVIPACT (NCT04366154) vise à décrire les adaptations de traitements oncologiques ou de prise en charge, et l’état psychologique des patients à différents temps de la pandémie. Nous présentons ici les résultats portant sur la prise en charge oncologique. Méthodes Les patients traités pour un cancer solide ou hématologique et reçus en hôpital de jour des deux centres de lutte contre le cancer de Normandie pendant la période du premier confinement (mars-mai 2020) ont été inclus. Les modifications thérapeutiques décidées lors de réunions de concertation pluridisciplinaires ont été recueillies dans les dossiers médicaux. Les facteurs cliniques associés à une adaptation de prise en charge ont été recherchés par des modèles de régression logistique. Résultats Au total, 734 patients ont été analysés, d’âge médian 64 ans [24-89] et comptant 69 % de femmes ; 724 (99 %) présentaient un cancer solide, dont 60 % au stade métastatique, et 49 % bénéficiaient d’un traitement de première ligne. Les patients étaient principalement traités par chimiothérapie seule (49 %), chimiothérapie associée à une thérapie ciblée (17 %), thérapie ciblée seule (19 %), ou immunothérapie seule (8 %), les autres recevant une combinaison de traitements ; 272 patients (37 %) ont commencé ce traitement pendant la période de confinement. Au total, 195 patients (27 %) ont eu une adaptation de traitement ou de prise en charge d’un ou plusieurs types, dont 29 % de décalages de cures, 27 % de modifications de suivi (principalement télé ou visio-consultation), 16 % d’interruptions de traitement et 27 % de modifications du rythme d’administration. Ces adaptations étaient significativement associées au type de traitement (p

Introduction Le confinement et le contexte sanitaire liés au COVID-19 peuvent entrainer une peur, une anxiété ou des troubles psychologiques s’apparentant à un syndrome de stress post traumatique (SSPT). Les patients traités pour un cancer apparaissent d’autant plus à risque de SSPT qu’ils doivent faire face à la fois à leur pathologie grave et à la peur de développer une forme sévère de COVID-19 dans un contexte social peu favorable pour les soutenir. Dans le cadre de l’étude COVIPACT, notre objectif était de décrire au cours du temps la prévalence des symptômes de SSPT chez les patients atteints de cancer, en lien avec des caractéristiques cliniques (date de diagnostic de cancer, traitements, adaptations de prise en charge liées à la pandémie COVID-19) et des mesures d’état de santé auto-déclarées (qualité de vie, insomnie et cognition). Méthodes L’étude COVIPACT (NCT04366154) a inclus 734 patients traités pour un cancer solide ou hématologique et reçus en hôpital de jour pendant la première période de confinement dans les deux Centres de lutte contre le cancer de Normandie. Les données cliniques ont été recueillies dans les dossiers médicaux. Des questionnaires validés ont permis de mesurer le stress post-traumatique (défini par un score à l’échelle IES-R ≥ 33), la qualité de vie (FACT-G, échelle 0-108), l’insomnie (ISI, échelle 0-28) et la cognition (FACT-Cog PCI, échelle 0-72) à l’inclusion (pendant le premier confinement, avril/mai 2020), à trois mois (déconfinement, juillet/août 2020) et à six mois (pendant le deuxième confinement, octobre/novembre 2020). Les facteurs associés au SSPT à l’inclusion et à son évolution au cours du temps ont été recherchés par des modèles de régression logistique à effets fixes et mixtes (prenant en compte la corrélation intra-individuelle entre mesures répétées). Résultats Les 578 (79 %) patients COVIPACT ayant répondu aux questionnaires à l’inclusion avaient en médiane 64 ans et 72 % étaient des femmes. Près de 95 % des patients présentaient une tumeur solide, dont la localisation primitive était principalement le sein (44 %), les poumons, la tête et le cou (20 %), le système digestif (17 %) et l’appareil génital féminin (11 %) et dont 59 % avaient un cancer métastatique. Un SSPT a été observé chez 21,3 % des patients au premier confinement (n = 120/565), 13,6 % des patients au moment du déconfinement (n = 46/339) et 23,5 % des patients durant le deuxième confinement (n = 76/322 ; p

O80:H2 enterohemorrhagic Escherichia coli (EHEC) of sequence type ST301 is one of the main serotypes causing European hemolytic and uremic syndrome, but also invasive infections, due to extra-intestinal virulence factors (VFs). Here, we determined whether other such heteropathotypes exist among ST301. EnteroBase was screened for ST301 strains that were included in a general SNP-phylogeny. French strains belonging to a new heteropathotype clone were sequenced. ST, hierarchical clusters (HC), serotype, resistome, and virulome were determined using EnteroBase, the CGE website, and local BLAST. The ST301 general phylogeny shows two groups. Group A (n = 25) is mainly composed of enteropathogenic E. coli, whereas group B (n = 55) includes mostly EHEC. Three serotypes, O186:H2, O45:H2 and O55:H9, share the same virulome as one of the O80:H2 sub-clones from which they derive subsequent O-antigen switches. The O55:H9 clone, mainly present in France (n = 29), as well as in the UK (n = 5) and Germany (n = 1), has a low background of genetic diversity (four HC20), although it has three Stx subtypes, an H-antigen switch, and genes encoding the major extra-intestinal VF yersiniabactin, and extended-spectrum beta-lactamases. Diverse heteropathotype clones genetically close to the O80:H2 clone are present among the ST301, requiring close European monitoring, especially the virulent O55:H9 clone.

Introduction Several nutrients may predict dementia risk. We characterized nutrient biomarker patterns, which integrate the complexity of nutrient exposure and biodisponibility associated with long-term risk of dementia in a large cohort of older persons, the Three-City study. Methods We included 666 nondemented participants with plasma measurements of 22 fat-soluble nutrients at baseline, who were followed up for 12 years for dementia. Results A "deleterious" pattern combining lower blood status in vitamin D, carotenoids, and polyunsaturated fats and higher saturated fats was strongly associated with a higher risk of dementia. Compared with individuals in the first quintile of the pattern score, participants in the highest quintile of score had an approximately fourfold increased risk of dementia (hazard ratio = 4.53 [95% confidence interval 1.99, 10.32], P for trend Discussion A blood pattern reflecting lower status in several nutrients among nondemented individuals appeared strongly associated with the long-term risk of dementia in this cohort.

We report an outbreak of Shiga toxin-producing Escherichia coli (STEC) associated paediatric haemolytic uraemic syndrome linked to the consumption of raw cow’s milk soft cheeses. From 25 March to 27 May 2019, 16 outbreak cases infected with STEC O26 (median age: 22 months) were identified. Interviews and trace-back investigations using loyalty cards identified the consumption of raw milk cheeses from a single producer. Trace-forward investigations revealed that these cheeses were internationally distributed.