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Since 2022, Europe has had 4 cases of extensively drug-resistant Neisseria gonorrhoeae, sequence type 16406, that is resistant to ceftriaxone and highly resistant to azithromycin. We report 2 new cases from France in 2023 involving strains genetically related to the 4 cases from Europe as well as isolates from Cambodia.

Abstract The ketogenic diet (KD) has been shown to be effective in refractory epilepsy after long-term administration. However, its interference with short-term brain metabolism and its involvement in the early process leading to epilepsy remain poorly understood. This study aimed to assess the effect of a short-term ketogenic diet on cerebral glucose metabolic changes, before and after status epilepticus (SE) in rats, by using [18F]-FDG PET. Thirty-nine rats were subjected to a one-week KD (KD-rats, n = 24) or to a standard diet (SD-rats, n = 15) before the induction of a status epilepticus (SE) by lithium-pilocarpine administrations. Brain [18F]-FDG PET scans were performed before and 4 h after this induction. Morphological MRIs were acquired and used to spatially normalize the PET images which were then analyzed voxel-wisely using a statistical parametric-based method. Twenty-six rats were analyzed (KD-rats, n = 15; SD-rats, n = 11). The 7 days of the KD were associated with significant increases in the plasma β-hydroxybutyrate level, but with an unchanged glycemia. The PET images, recorded after the KD and before SE induction, showed an increased metabolism within sites involved in the appetitive behaviors: hypothalamic areas and periaqueductal gray, whereas no area of decreased metabolism was observed. At the 4th hour following the SE induction, large metabolism increases were observed in the KD- and SD-rats in areas known to be involved in the epileptogenesis process late—i.e., the hippocampus, parahippocampic, thalamic and hypothalamic areas, the periaqueductal gray, and the limbic structures (and in the motor cortex for the KD-rats only). However, no statistically significant difference was observed when comparing SD and KD groups at the 4th hour following the SE induction. A one-week ketogenic diet does not prevent the status epilepticus (SE) and associated metabolic brain abnormalities in the lithium-pilocarpine rat model. Further explorations are needed to determine whether a significant prevention could be achieved by more prolonged ketogenic diets and by testing this diet in less severe experimental models, and moreover, to analyze the diet effects on the later and chronic stages leading to epileptogenesis.

Abstract This study assesses the feasibility of using a sample-efficient model to investigate radiomics changes over time for predicting progression-free survival in rare diseases. Eighteen high-grade glioma patients underwent two L-3,4-dihydroxy-6-[18F]-fluoro-phenylalanine positron emission tomography (PET) dynamic scans: the first during treatment and the second at temozolomide chemotherapy discontinuation. Radiomics features from static/dynamic parametric images, alongside conventional features, were extracted. After excluding highly correlated features, 16 different models were trained by combining various feature selection methods and time-to-event survival algorithms. Performance was assessed using cross-validation. To evaluate model robustness, an additional dataset including 35 patients with a single PET scan at therapy discontinuation was used. Model performance was compared with a strategy extracting informative features from the set of 35 patients and applying them to the 18 patients with 2 PET scans. Delta-absolute radiomics achieved the highest performance when the pipeline was directly applied to the 18-patient subset (support vector machine (SVM) and recursive feature elimination (RFE): C-index = 0.783 [0.744–0.818]). This result remained consistent when transferring informative features from 35 patients (SVM + RFE: C-index = 0.751 [0.716–0.784], p = 0.06). In addition, it significantly outperformed delta-absolute conventional (C-index = 0.584 [0.548–0.620], p

Abstract Inborn metabolic diseases (IMD) are rare conditions that can be diagnosed during adulthood. Patients with IMD may have joint symptoms and the challenge is to establish an early diagnosis in order to institute appropriate treatment and prevent irreversible damage. This review describes the joint manifestations of IMD that may be encountered in adults. The clinical settings considered were arthralgia and joint stiffness as well as arthritis. Unspecific arthralgias are often the first symptoms of hereditary hemochromatosis, chronic low back pain may reveal an intervertebral disc calcification in relation with alkaptonuria, and progressive joint stiffness may correspond to a mucopolysaccharidosis or mucolipidosis. Gaucher disease is initially revealed by painful acute attacks mimicking joint pain described as “bone crises”. Some IMD may induce microcrystalline arthropathy. Beyond classical gout, there are also gouts in connection with purine metabolism disorders known as “enzymopathic gouts”. Pyrophosphate arthropathy can also be part of the clinical spectrum of Gitelman syndrome or hypophosphatasia. Oxalate crystals arthritis can reveal a primary hyperoxaluria. Destructive arthritis may be indicative of Wilson’s disease. Non-destructive arthritis may be seen in mevalonate kinase deficiency and familial hypercholesterolemia.

Introduction Aseptic abscess (AA) syndrome is a rare disease whose pathophysiology is unknown. It is often associated with inflammatory bowel disease and characterised by sterile inflammation with collections of neutrophils affecting several organs, especially the spleen. Microbiota are known to influence local and systemic immune responses, and both gut and oral microbiota perturbations have been reported in diseases associated with AA syndrome. However, interactions between these factors have never been studied in AA syndrome. The purpose of this translational case-control study (ABSCESSBIOT) is to investigate gut and/or oral microbiota in patients with AA syndrome compared with healthy controls. Moreover, microbiota associated metabolites quantification and Treg/Th17 balance characterisation will give a mechanistic insight on how microbiota may be involved in the pathophysiology of AA syndrome.Methods and analysis This French multicentre case-control study including 30 French centres (University hospital or regional hospital) aims to prospectively enrol 30 patients with AA syndrome with 30 matched controls and to analyse microbiota profiling (in stools and saliva), microbial metabolites quantification in stools and circulating CD4+ T cell populations.Ethics and dissemination This study protocol was reviewed and approved by an independent French regional review board (n° 2017-A03499-44, Comité de Protection des Personnes Ile de France 1) on 10 October 2022, and declared to the competent French authority (Agence Nationale de Sécurité du Médicament et des produits de santé, France). Oral and written informed consent will be obtained from each included patient and the control participant. Study results will be reported to the scientific community at conferences and in peer-reviewed scientific journals.Trial registration number Clinical Trials web-based platform (NCT05537909).

Objectives In this large multicentre study, we compared the effectiveness and safety of tocilizumab intravenous versus subcutaneous (SC) in 109 Takayasu arteritis (TAK) patients.Methods We conducted a retrospective multicentre study in referral centres from France, Italy, Spain, Armenia, Israel, Japan, Tunisia and Russia regarding biological-targeted therapies in TAK, since January 2017 to September 2019.Results A total of 109 TAK patients received at least 3 months tocilizumab therapy and were included in this study. Among them, 91 and 18 patients received intravenous and SC tocilizumab, respectively. A complete response (NIH

ObjectiveWe aimed to investigate whether anakinra, an interleukin-1receptor inhibitor, could improve outcome in moderate COVID-19 patients.MethodsIn this controlled, open-label trial, we enrolled adults with COVID-19 requiring oxygen. We randomly assigned patients to receive intravenous anakinra plus optimized standard of care (oSOC) vs. oSOC alone. The primary outcome was treatment success at day 14 defined as patient alive and not requiring mechanical ventilation or extracorporeal membrane oxygenation.ResultsBetween 27th April and 6th October 2020, we enrolled 71 patients (240 patients planned to been enrolled): 37 were assigned to the anakinra group and 34 to oSOC group. The study ended prematurely by recommendation of the data and safety monitoring board due to safety concerns. On day 14, the proportion of treatment success was significantly lower in the anakinra group 70% (n = 26) vs. 91% (n = 31) in the oSOC group: risk difference-21 percentage points (95% CI, -39 to -2), odds ratio 0.23 (95% CI, 0.06 to 0.91), p = 0.027. After a 28-day follow-up, 9 patients in the anakinra group and 3 in the oSOC group had died. Overall survival at day 28 was 75% (95% CI, 62% to 91%) in the anakinra group versus 91% (95% CI, 82% to 100%) (p = 0.06) in the oSOC group. Serious adverse events occurred in 19 (51%) patients in the anakinra group and 18 (53%) in the oSOC group (p = 0·89).ConclusionThis trial did not show efficacy of anakinra in patients with COVID-19. Furthermore, contrary to our hypothesis, we found that anakinra was inferior to oSOC in patients with moderate COVID-19 pneumonia.

General practitioners (GPs) play a critical role in patient acceptance of vaccination. Vaccine hesitancy (VH) is a growing phenomenon in the general population but also affects GPs. Few data exist on VH among GPs. The objectives of this analysis of a population of GPs in the Belgian Wallonia-Brussels Federation (WBF) were to: (1) determine the prevalence and the features of VH, (2) identify the correlates, and (3) estimate the discrepancy in vaccination’s behaviors between the GPs’ children and the recommendations made to their patients. An online survey was carried out among the population of general practitioners practicing in the WBF between 7 January and 18 March 2020. A hierarchical cluster analysis was carried out based on various dimensions of vaccine hesitancy: perception of the risks and the usefulness of vaccines as well as vaccine recommendations for their patients. A total of 251 GPs answered the survey. The average percentage of moderate to high vaccine hesitancy was 50.6%. Three factors were independently associated with increased risk of vaccine hesitancy: an age

Background: Public trust in immunization is an increasingly important global health issue. Losses in confidence in vaccines and immunization programmes can lead to vaccine reluctance and refusal, risking disease outbreaks and challenging immunization goals in high- and low-income settings. National and international immunization stakeholders have called for better monitoring of vaccine confidence to identify emerging concerns before they evolve into vaccine confidence crises. Methods: We perform a large-scale, data-driven study on worldwide attitudes to immunizations. This survey – which we believe represents the largest survey on confidence in immunization to date – examines perceptions of vaccine importance, safety, effectiveness, and religious compatibility among 65,819 individuals across 67 countries. Hierarchical models are employed to probe relationships between individual- and country-level socio-economic factors and vaccine attitudes obtained through the four-question, Likert-scale survey. Findings: Overall sentiment towards vaccinations is positive across all 67 countries, however there is wide variability between countries and across world regions. Vaccine-safety related sentiment is particularly negative in the European region, which has seven of the ten least confident countries, with 41% of respondents in France and 36% of respondents in Bosnia & Herzegovina reporting that they disagree that vaccines are safe (compared to a global average of 13%). The oldest age group (65+) and Roman Catholics (amongst all faiths surveyed) are associated with positive views on vaccine sentiment, while the Western Pacific region reported the highest level of religious incompatibility with vaccines. Countries with high levels of schooling and good access to health services are associated with lower rates of positive sentiment, pointing to an emerging inverse relationship between vaccine sentiments and socio-economic status. Conclusions: Regular monitoring of vaccine attitudes – coupled with monitoring of local immunization rates – at the national and sub-national levels can identify populations with declining confidence and acceptance. These populations should be prioritized to further investigate the drivers of negative sentiment and to inform appropriate interventions to prevent adverse public health outcomes.

We report an outbreak of canine visceral leishmaniasis in Uruguay. Blood specimens from 11/45 dogs tested positive for Leishmania spp. Specimens of Lutzomyia longipalpis sand flies were captured; typing revealed Leishmania infantum. Our findings document an expansion of visceral leishmaniasis to southern South America and risk for vectorborne transmission to humans.

Recent emphasis has been placed on the role that cerebellar dysfunctions could have in the genesis of cognitive deficits in Duchenne muscular dystrophy (DMD). However, relevant genotype-phenotype analyses are missing to define whether cerebellar defects underlie the severe cases of intellectual deficiency that have been associated with genetic loss of the smallest product of the dmd gene, the Dp71 dystrophin. To determine for the first time whether Dp71 loss could affect cerebellar physiology and functions, we have used patch-clamp electrophysiological recordings in acute cerebellar slices and a cerebellum-dependent behavioral test battery addressing cerebellum-dependent motor and non-motor functions in Dp71-null transgenic mice. We found that Dp71 deficiency selectively enhances excitatory transmission at glutamatergic synapses formed by climbing fibers (CFs) on Purkinje neurons, but not at those formed by parallel fibers. Altered basal neurotransmission at CFs was associated with impairments in synaptic plasticity and clustering of the scaffolding postsynaptic density protein PSD-95. At the behavioral level, Dp71-null mice showed some improvements in motor coordination and were unimpaired for muscle force, static and dynamic equilibrium, motivation in high-motor demand and synchronization learning. Dp71-null mice displayed altered strategies in goal-oriented navigation tasks, however, suggesting a deficit in the cerebellum-dependent processing of the procedural components of spatial learning, which could contribute to the visuospatial deficits identified in this model. In all, the observed deficits suggest that Dp71 loss alters cerebellar synapse function and cerebellum-dependent navigation strategies without being detrimental for motor functions.

Mechanical forces have emerged as coordinating signals for most cell functions. Yet, because forces are invisible, mapping tensile stress patterns in tissues remains a major challenge in all kingdoms. Here we take advantage of the adhesion defects in the Arabidopsis mutant quasimodo1 (qua1) to deduce stress patterns in tissues. By reducing the water potential and epidermal tension in planta, we rescued the adhesion defects in qua1, formally associating gaping and tensile stress patterns in the mutant. Using suboptimal water potential conditions, we revealed the relative contributions of shape- and growth-derived stress in prescribing maximal tension directions in aerial tissues. Consistently, the tension patterns deduced from the gaping patterns in qua1 matched the pattern of cortical microtubules, which are thought to align with maximal tension, in wild-type organs. Conversely, loss of epidermis continuity in the qua1 mutant hampered supracellular microtubule alignments, revealing that coordination through tensile stress requires cell-cell adhesion.

The shape and function of plant cells are often highly interdependent. The puzzle-shaped cells that appear in the epidermis of many plants are a striking example of a complex cell shape, however their functional benefit has remained elusive. We propose that these intricate forms provide an effective strategy to reduce mechanical stress in the cell wall of the epidermis. When tissue-level growth is isotropic, we hypothesize that lobes emerge at the cellular level to prevent formation of large isodiametric cells that would bulge under the stress produced by turgor pressure. Data from various plant organs and species support the relationship between lobes and growth isotropy, which we test with mutants where growth direction is perturbed. Using simulation models we show that a mechanism actively regulating cellular stress plausibly reproduces the development of epidermal cell shape. Together, our results suggest that mechanical stress is a key driver of cell-shape morphogenesis.

INTRODUCTION:Aim was to develop a full automatic clustering approach of the time-activity curves (TAC) from dynamic 18F-FET PET and evaluate its association with IDH1 mutation status and survival in patients with gliomas. METHODS:Thirty-seven patients (mean age: 45±13 y) with newly diagnosed gliomas and dynamic 18F-FET PET before any histopathologic investigation or treatment were retrospectively included. Each dynamic 18F-FET PET was realigned to the first image and spatially normalized in the Montreal Neurological Institute template. A tumor mask was semi-automatically generated from Z-score maps. Each brain tumor voxel was clustered in one of the 3 following centroids using dynamic time warping and k-means clustering (centroid #1: slowly increasing slope; centroid #2: rapidly increasing followed by slowly decreasing slope; and centroid #3: rapidly increasing followed by rapidly decreasing slope). The percentage of each dynamic 18F-FET TAC within tumors and other conventional 18F-FET PET parameters (maximum and mean tumor-to-brain ratios [TBRmax and TBRmean], time-to-peak [TTP] and slope) was compared between wild-type and IDH1 mutant tumors. Their prognostic value was assessed in terms of progression free-survival (PFS) and overall survival (OS) by Kaplan-Meier estimates. RESULTS:Twenty patients were IDH1 wild-type and 17 IDH1 mutant. Higher percentage of centroid #1 and centroid #3 within tumors were positively (P = 0.016) and negatively (P = 0.01) correlated with IDH1 mutated status. Also, TBRmax, TBRmean, TTP, and slope discriminated significantly between tumors with and without IDH1 mutation (P range 0.01 to 0.04). Progression occurred in 22 patients (59%) at a median of 13.1 months (7.6-37.6 months) and 13 patients (35%) died from tumor progression. Patients with a percentage of centroid #1 > 90% had a longer survival compared with those with a percentage of centroid #1 < 90% (P = 0.003 for PFS and P = 0.028 for OS). This remained significant after stratification on IDH1 mutation status (P = 0.029 for PFS and P = 0.034 for OS). Compared to other conventional 18F-FET PET parameters, TTP and slope were associated with PFS and OS (P range 0.009 to 0.04). CONCLUSIONS:Based on dynamic 18F-FET PET acquisition, we developed a full automatic clustering approach of TAC which appears to be a valuable noninvasive diagnostic and prognostic marker in patients with gliomas.

French general practitioners (GPs) refer their patients with major depression to psychiatrists or for psychotherapy at particularly low rates.This qualitative study aims to explore general practitioners' (GP) opinions about psychotherapy, their relationships with mental health professionals, their perceptions of their role and that of psychiatrists in treating depression, and the relations between these factors and the GPs' strategies for managing depression.In 2011, in-depth interviews based on a semi-structured interview guide were conducted with 32 GPs practicing in southeastern France. Verbatim transcripts were examined by analyzing their thematic content.We identified three profiles of physicians according to their opinions and practices about treatment strategies for depression: pro-pharmacological treatment, pro-psychotherapy and those with mixed practices. Most participants considered their relationships with psychiatrists unsatisfactory, would like more and better collaboration with them and shared the same concept of management in general practice. This concept was based both on the values and principles of practice shared by GPs and on their strong differentiation of their management practices from those of psychiatrists.Several attitudes and values common to GPs might contribute to their low rate of referrals for psychotherapy in France: strong occupational identity, substantial variations in GPs' attitudes and practices regarding depression treatment strategies, representations sometimes unfavorable toward psychiatrists. Actions to develop a common culture and improve cooperation between GPs and psychiatrists are essential. They include systems of collaborative care and the development of interdisciplinary training common to GPs and psychiatrists practicing in the same area.

During pregnancy, the diet of a mother-to-be should be adapted to meet increases in nutrient requirements. We analyzed the theoretical efficiency and acceptability of different types of tailored dietary changes for pregnant women.The nutrient adequacy of the diet was evaluated using the PANDiet score, by comparing the nutrient intakes of 344 non-pregnant premenopausal women (18-44y) with dietary reference intakes for the first trimester of pregnancy. Simulations were performed to evaluate the theoretical efficiency of three types of ten successive tailored dietary changes in improving nutrient adequacy, with graded difficulty in implementation. The acceptability (declared intention to use in the diet) of most efficient dietary changes was evaluated during an online randomized study including 115 French pregnant women (22-41y).Modifying the amount consumed of foods (type-1) did not modify the food repertoire and resulted in the smallest theoretical efficiency (increase in the PANDiet score of 9.8±0.2 points), but changes were the most acceptable (probability of the intention to use: 0.30-0.78). Conversely, replacing food items by items from the same group or eaten at the same time (type-3) broadened the food repertoire (3.6±1.3 food subgroups added) and resulted in the greatest theoretical efficiency (+23.9±0.3) but changes were the least acceptable (0.07-0.23). Replacing food items within the same subgroup (type-2) slightly broadened the food repertoire (+8.0±1.3 foods) and resulted in moderate theoretical efficiency (+14.8±0.2) and intermediate acceptability (0.11-0.35).A clear trade-off exists between the theoretical efficiency and acceptability of dietary changes, with a graded broadening of the food repertoire.

Knowledge of the host range of a biocontrol agent (BCA) is fundamental. Host range determines the BCA's economic potential, as well as the possible risk for non-target organisms. Entomopathogenic fungal strains belonging to the genus Beauveria are widely used as BCA, but our knowledge of their physiological host range is only partial. The aim of this study was to improve our understanding of the physiological host range of three Beauveria strains belonging to two species, B. hoplocheli and B. bassiana. We performed laboratory mortality bioassays to assess their pathogenicity and virulence against nine insect pests, belonging to three orders: Lepidoptera, Coleoptera and Diptera. Mortality rate, mean survival time and mycosis rate were used to estimate virulence. Pathogenicity was assessed as the capacity to cause a disease and induce mortality. Virulence was assessed as the severity of the disease based on mortality rate, mean survival time and mycosis rate. The results of this study revealed significant differences in the physiological host range of the three Beauveria strains tested. The three strains were pathogenic to all Diptera and Lepidoptera species tested. In the case of the Coleoptera, only the B. hoplocheli strain was pathogenic to the white grub Hoplochelus marginalis and only the B. bassiana strains were pathogenic to Alphitobius diaperinus. The B. hoplocheli strain was less virulent on Lepidoptera and Diptera than the two B. bassiana strains. The latter both exhibited very similar virulence patterns. The fact that B. hoplocheli and B. bassiana strains have different host ranges means that they can be used as BCA to target different pests. Impacts on non-target insects across multiple orders cannot be ruled out in the absence of ecological host range studies.

Continuous contact with self-major histocompatibility complex ligands is essential for the survival of naive CD4 T cells. We have previously shown that the resulting tonic TCR signaling also influences their fate upon activation by increasing their ability to differentiate into induced/peripheral regulatory T cells. To decipher the molecular mechanisms governing this process, we here focus on the TCR signaling cascade and demonstrate that a rise in intracellular calcium levels is sufficient to modulate the phenotype of mouse naive CD4 T cells and to increase their sensitivity to regulatory T-cell polarization signals, both processes relying on calcineurin activation. Accordingly, in vivo calcineurin inhibition leads the most self-reactive naive CD4 T cells to adopt the phenotype of their less self-reactive cell-counterparts. Collectively, our findings demonstrate that calcium-mediated activation of the calcineurin pathway acts as a rheostat to shape both the phenotype and effector potential of naive CD4 T cells in the steady-state.

Background: This study aimed to assess: 1) vaccine hesitancy (VH) prevalence among French general practitioners (GPs) through the frequency of their vaccine recommendations, and 2) the determinants of these recommendations. Methods: Cross-sectional observational study in 2014 nested in a national panel of 1712 randomly selected GPs in private practice in France. We constructed a score of self-reported recommendation frequency for 6 specific vaccines to target populations. Results: 16% to 43% of GPs sometimes or never recommended at least one specific vaccine to their target patients. Multivariable logistic regressions of the dichotomized score showed that GPs recommended vaccines frequently when they felt comfortable explaining their benefits and risks to patients (OR = 1.87; 1.35–2.59), or trusted official sources of information highly (OR = 1.40; 1.01–1.93). They recommended vaccines infrequently when they considered that adverse effects were likely (OR = 0.71; 0.52–0.96) or doubted the vaccine's utility (OR = 0.21; 0.15–0.29). Interpretation: Our findings show that after repeated vaccine controversies in France, some VH exists among French GPs, whose recommendation behaviors depend on their trust in authorities, their perception of the utility and risks of vaccines, and their comfort in explaining them. Further research is needed to confirm these results among health care workers in other countries.

Macrophagic myofasciitis (MMF) is an emerging condition with highly specific myopathological alterations. A peculiar spatial pattern of a cerebral glucose hypometabolism involving occipito-temporal cortex and cerebellum have been reported in patients with MMF; however, the full pattern is not systematically present in routine interpretation of scans, and with varying degrees of severity depending on the cognitive profile of patients. Aim was to generate and evaluate a support vector machine (SVM) procedure to classify patients between healthy or MMF 18F-FDG brain profiles.18F-FDG PET brain images of 119 patients with MMF and 64 healthy subjects were retrospectively analyzed. The whole-population was divided into two groups; a training set (100 MMF, 44 healthy subjects) and a testing set (19 MMF, 20 healthy subjects). Dimensionality reduction was performed using a t-map from statistical parametric mapping (SPM) and a SVM with a linear kernel was trained on the training set. To evaluate the performance of the SVM classifier, values of sensitivity (Se), specificity (Sp), positive predictive value (PPV), negative predictive value (NPV) and accuracy (Acc) were calculated.The SPM12 analysis on the training set exhibited the already reported hypometabolism pattern involving occipito-temporal and fronto-parietal cortices, limbic system and cerebellum. The SVM procedure, based on the t-test mask generated from the training set, correctly classified MMF patients of the testing set with following Se, Sp, PPV, NPV and Acc: 89%, 85%, 85%, 89%, and 87%.We developed an original and individual approach including a SVM to classify patients between healthy or MMF metabolic brain profiles using 18F-FDG-PET. Machine learning algorithms are promising for computer-aided diagnosis but will need further validation in prospective cohorts.

The authors wish to make the following corrections to their paper [...]

In the framework of the first multi-centre Sub-Saharan Africa Total Diet Study (SSA-TDS), 2328 commonly consumed foods were purchased, prepared as consumed and pooled into 194 composite samples of cereals, tubers, legumes, vegetables, nuts and seeds, dairy, oils, beverages and miscellaneous. Those core foods were tested for mycotoxins and other fungal, bacterial and plant secondary metabolites by liquid chromatography, coupled with tandem mass spectrometry. The highest aflatoxin concentrations were quantified in peanuts, peanut oil and maize. The mean concentration of the sum of aflatoxins AFB1, AFB2, AFG1 and AFG2 (AFtot) in peanut samples (56.4 µg/kg) exceeded EU (4 µg/kg) and Codex (15 µg/kg) standards. The AFtot concentration (max: 246.0 µg/kg) was associated with seasonal and geographic patterns and comprised, on average, 80% AFB1, the most potent aflatoxin. Although ochratoxin A concentrations rarely exceeded existing Codex standards, it was detected in unregulated foods. One palm oil composite sample contained 98 different metabolites, including 35.4 µg/kg of ochratoxin A. In total, 164 different metabolites were detected, with unspecific metabolites like asperglaucide, cyclo(L-pro-L-val), cyclo (L-pro-L-tyr), flavoglaucin, emodin and tryptophol occurring in more than 50% of composite samples. Aflatoxin B1 (AFB1), fumonisin B1 (FB1), sterigmatocystin (STC), ochratoxin A (OTA), citrinin (CIT) and many other secondary fungal metabolites are frequent co-contaminants in staple foods, such as maize and sorghum. Populations from North Cameroon and from Benin may, therefore, suffer chronic and simultaneous exposure to AFB1, FB1, STC, OTA and CIT, which are prevalent in their diet.

BACKGROUND:Maternal nutrition is critical to the health of both mother and offspring, but there is a paucity of data on the nutritional adequacy of diets during pregnancy. OBJECTIVE:Our objective was to identify to what extent pregnancy reduces the nutritional adequacy of the expecting mother's diet and if this nutritional gap can be resolved by simple quantitative or qualitative changes in the diet. MATERIALS AND METHODS:We evaluated the observed overall nutritional adequacy of diets of French and American women of childbearing age participating in ENNS (n = 344) and NHANES (n = 563) using the probabilistic approach of the PANDiet system, resulting in a 100-point score. Then, we simulated the changes in the PANDiet scores of women of childbearing age who would remain on their diet during pregnancy. Finally, by either increasing the quantity of consumed foods or using eleven snacks recommended during pregnancy, we simulated the effect of a 150-kcal increase in the energy intake of French women. RESULTS:Observed PANDiet scores were equal to 59.3 ± 7.0 and 58.8 ± 9.3 points respectively in France and in the US. Simulation of pregnancy for women of childbearing age led to a decrease in nutritional adequacy for key nutrients during pregnancy and resulted in reducing PANDiet scores by 3.3 ± 0.1 and 3.7 ± 0.1 points in France and in the US. Simulated 150-kcal increases in energy intake proved to be only partially effective in filling the gap both when the quantity of food consumed was increased and when recommended snacks were used. CONCLUSIONS:The decrease in nutritional adequacy induced by pregnancy cannot be addressed by simply following generic dietary guidelines.

OBJECTIVE:To investigate association between genetic polymorphisms of GST, CYP and renal outcome or occurrence of adverse drug reactions (ADRs) in lupus nephritis (LN) treated with cyclophosphamide (CYC). CYC, as a pro-drug, requires bioactivation through multiple hepatic cytochrome P450s and glutathione S transferases (GST). METHODS:We carried out a multicentric retrospective study including 70 patients with proliferative LN treated with CYC. Patients were genotyped for polymorphisms of the CYP2B6, CYP2C19, GSTP1, GSTM1 and GSTT1 genes. Complete remission (CR) was defined as proteinuria ≤0.33g/day and serum creatinine ≤124 µmol/l. Partial remission (PR) was defined as proteinuria ≤1.5g/day with a 50% decrease of the baseline proteinuria value and serum creatinine no greater than 25% above baseline. RESULTS:Most patients were women (84%) and 77% were Caucasian. The mean age at LN diagnosis was 41 ± 10 years. The frequency of patients carrying the GST null genotype GSTT1-, GSTM1-, and the Ile→105Val GSTP1 genotype were respectively 38%, 60% and 44%. In multivariate analysis, the Ile→105Val GSTP1 genotype was an independent factor of poor renal outcome (achievement of CR or PR) (OR = 5.01 95% CI [1.02-24.51]) and the sole factor that influenced occurrence of ADRs was the GSTM1 null genotype (OR = 3.34 95% CI [1.064-10.58]). No association between polymorphisms of cytochrome P450s gene and efficacy or ADRs was observed. CONCLUSION:This study suggests that GST polymorphisms highly impact renal outcome and occurrence of ADRs related to CYC in LN patients.

This work aims to develop, validate and optimize the radiolabeling of Starch-Based Microparticles (SBMP) by 188Re and 68Ga in the form of ready-to-use radiolabeling kits, the ultimate goal being to obtain a unique theranostic vector for the treatment of Hepatocellular Carcinoma.Optimal labeling conditions and composition of freeze-dried kits were defined by monitoring the radiochemical purity while varying several parameters. In vitro stability studies were carried out, as well as an in vivo biodistribution as a preliminary approach with the intra-arterial injection of 68Ga radiolabeled SBMP into the hepatic artery of DENA-induced rats followed by PET/CT imaging.Kits were optimized for 188Re and 68Ga with high and stable radiochemical purity (>95% and >98% respectively). The in vivo preliminary study was successful with more than 95% of activity found in the liver and mostly in the tumorous part.SBMP are a promising theranostic agent for the Selective Internal Radiation Therapy of Hepatocellular carcinoma.

BACKGROUND:The number of morbidly obese patients undergoing bariatric surgery (BS) has increased dramatically in recent years. Therefore, monitoring food intake and its consequences in terms of nutritional status is necessary to prevent nutritional deficiencies. The aim of this study was to analyze the effect of food restriction on nutritional parameters in the short-term (≤3 months) period after BS in morbid obesity. METHOD:In a prospective study, we followed 22 obese women who underwent Roux-en-Y gastric bypass (GBP) or adjustable gastric banding (AGB) at baseline (T0) and 1 (T1) and 3 (T3) months after surgery. We evaluated food intake, nutrient adequacy and serum concentrations of vitamins and minerals known to be at risk for deficiency following BS. RESULTS:Before surgery, we observed suboptimal food intakes, leading to a risk of micronutrient deficiencies. Serum analysis confirmed nutritional deficiencies for iron and thiamine for 27 and 23% of the patients, respectively. The drastic energy and food reduction seen in the short term led to very low probabilities of adequacy for nutrients equivalent across both surgeries. Serum analysis demonstrated a continuous decrease in prealbumin during the follow-up, indicating mild protein depletion in 21 and 57% of GBP patients and 50 and 63% of AGB patients, respectively, at T1 and T3. Regarding vitamins and minerals, systematic supplementation after GBP prevented most nutritional deficiencies. By contrast, AGB patients, for whom there is no systematic supplementation, developed such deficiencies. CONCLUSIONS:Our results suggest that cautious monitoring of protein intake after BS is mandatory. Furthermore, AGB patients might also benefit from systematic multivitamin and mineral supplementation at least in the short term.

Background Chemical exposures have been associated with a variety of health effects; however, little is known about the global disease burden from foodborne chemicals. Food can be a major pathway for the general population’s exposure to chemicals, and for some chemicals, it accounts for almost 100% of exposure. Methods and Findings Groups of foodborne chemicals, both natural and anthropogenic, were evaluated for their ability to contribute to the burden of disease. The results of the analyses on four chemicals are presented here - cyanide in cassava, peanut allergen, aflatoxin, and dioxin. Systematic reviews of the literature were conducted to develop age- and sex-specific disease incidence and mortality estimates due to these chemicals. From these estimates, the numbers of cases, deaths and disability adjusted life years (DALYs) were calculated. For these four chemicals combined, the total number of illnesses, deaths, and DALYs in 2010 is estimated to be 339,000 (95% uncertainty interval [UI]: 186,000-1,239,000); 20,000 (95% UI: 8,000-52,000); and 1,012,000 (95% UI: 562,000-2,822,000), respectively. Both cyanide in cassava and aflatoxin are associated with diseases with high case-fatality ratios. Virtually all human exposure to these four chemicals is through the food supply. Conclusion Chemicals in the food supply, as evidenced by the results for only four chemicals, can have a significant impact on the global burden of disease. The case-fatality rates for these four chemicals range from low (e.g., peanut allergen) to extremely high (aflatoxin and liver cancer). The effects associated with these four chemicals are neurologic (cyanide in cassava), cancer (aflatoxin), allergic response (peanut allergen), endocrine (dioxin), and reproductive (dioxin).

BACKGROUND: General practitioners (GPs) have a key role to play in suicide prevention, but the rates at which they question patients with depression about suicidal thoughts and plans are rather low. Little is known about GPs' characteristics associated with such inquiries. Our objectives were to describe GPs' attitudes, perceived barriers, and self-reported practices in this questioning of these patients and to analyze factors associated with these practices. METHODOLOGY: This cross-sectional survey was conducted among participants in a panel of randomly selected French GPs (1249/1431 participated: 87.3%). GPs were interviewed with a standardized questionnaire covering their professional and personal characteristics, attitudes, and practices in exploring the suicide risk of their patients with depression. We built a suicide inquiry score by summing the responses to 5 items and used a multiple linear regression analysis to explore the characteristics associated with this score. PRINCIPAL FINDINGS: Most GPs reported inquiring about the presence of suicidal ideation often or very often; less than 30% reported that they frequently explored signs of a specific suicide plan. The mean suicide inquiry score was 12.4 (SD, 2.9; range, 5-20). False ideas, such as thinking that patients who report suicidal ideas do not often commit suicide, were frequent (42.3%). Previous continuing medical education on suicide, participation in a formal mental health network, and patients who committed suicide in the past 5 years were associated with a higher score. Reluctance to question patients about suicide and perception of insufficient skill were associated with a lower score. CONCLUSIONS/SIGNIFICANCE: This study showed great variability in French GPs' practices in exploring suicide risk in patients with depression. Interventions aiming at improving GPs' initial training and continuing medical education in suicide and/or depression, and their collaboration with mental health specialists should be developed, and their impacts assessed.

BACKGROUND: In developed countries, primary care physicians manage most patients with depression. Relatively few studies allow a comprehensive assessment of the decisions these doctors make in these cases and the factors associated with these decisions. We studied how general practitioners (GPs) manage the acute phase of a new episode of non-comorbid major depression (MD) and the factors associated with their decisions. METHODOLOGY/PRINCIPAL FINDINGS: In this cross-sectional telephone survey, professional investigators interviewed an existing panel of randomly selected GPs (1249/1431, response rate: 87.3%). We used case-vignettes about new MD episodes in 8 versions differing by patient gender and socioeconomic status (blue/white collar) and disease intensity (mild/severe). GPs were randomized to receive one of these 8 versions. Overall, 82.6% chose pharmacotherapy; among them GPs chose either an antidepressant (79.8%) or an anxiolytic/hypnotic alone (18.5%). They rarely recommended referral for psychotherapy alone, regardless of severity, but 38.2% chose it in combination with pharmacotherapy. Antidepressant prescription was associated with severity of depression (OR = 1.74; 95%CI = 1.33-2.27), patient gender (female, OR = 0.75; 95%CI = 0.58-0.98), GP personal characteristics (e.g. history of antidepressant treatment: OR = 2.31; 95%CI = 1.41-3.81) and GP belief that antidepressants are overprescribed in France (OR = 0.63; 95%CI = 0.48-0.82). The combination of antidepressants and psychotherapy was associated with severity of depression (OR = 1.82; 95%CI = 1.31-2.52), patient's white-collar status (OR = 1.58; 95%CI = 1.14-2.18), and GPs' dissatisfaction with cooperation with mental health specialists (OR = 0.63; 95%CI = 0.45-0.89). These choices were not associated with either GPs' professional characteristics or psychiatrist density in the GP's practice areas. CONCLUSIONS/SIGNIFICANCE: GPs' choices for treating severe MD complied with clinical guidelines better than those for mild MD; GPs rarely recommended psychotherapy alone but rather as a complement to pharmacotherapy. Their decisions were mainly influenced by personal life experience and attitudes regarding treatment more than by professional characteristics. These results call into question the methods and content of continuing medical education in France about MD management.

BACKGROUND: In July, 2009, French health authorities, like those in many other countries, decided to embark on a mass vaccination campaign against the pandemic A(H1N1) influenza. Private general practitioners (GPs) were not involved in this campaign. We studied GPs' pandemic vaccine (pvaccine) uptake, quantified the relative contribution of its potential explanatory factors and studied whether their own vaccination choice was correlated with their recommendations to patients about pvaccination. METHODOLOGY/PRINCIPAL FINDINGS: In this cross-sectional telephone survey, professional investigators interviewed an existing panel of randomly selected private GPs (N = 1431; response rate at inclusion in the panel: 36.8%; participation rate in the survey: 100%). The main outcome variable was GPs' own pvaccine uptake. We used an averaging multi-model approach to quantify the relative contribution of factors associated with their vaccination. The pvaccine uptake rate was 61% (95%CI = 58.3-63.3). Four independent factors contributed the most to this rate (partial Nagelkerke's R(2)): history of previous vaccination against seasonal influenza (14.5%), perception of risks and efficacy of the pvaccine (10.8%), opinions regarding the organization of the vaccination campaign (7.1%), and perception of the pandemic's severity (5.2%). Overall, 71.3% (95%CI = 69.0-73.6) of the participants recommended pvaccination to young adults at risk and 40.1% (95%CI = 37.6-42.7) to other young adults. GPs' own pvaccination was strongly predictive of their recommendation to both young adults at risk (OR = 9.6; 95%CI = 7.2-12.6) and those not at risk (OR = 8.5; 95%CI = 6.4-11.4). CONCLUSIONS/SIGNIFICANCE: These results suggest that around 60% of French private GPs followed French authorities' recommendations about vaccination of health care professionals against the A(H1N1) influenza. They pinpoint priority levers for improving preparedness for future influenza pandemics. Besides encouraging GPs' own uptake of regular vaccination against seasonal influenza, providing GPs with clear information about the risks and efficacy of any new pvaccine and involving them in the organization of any future vaccine campaign may improve their pvaccine uptake.

In the context of studies on the effects of agricultural production diversity, there are debates in the scientific community as to the level of diversification appropriate for improving dietary diversity. In Tunisia, agriculture is a strategic sector for the economy and a critical pillar of its food sovereignty. Using instrumental variable methods to account for endogeneity, we have estimated the association between agricultural production diversity and women's dietary diversity among smallholder farming households in the Sidi Bouzid governorate (central Tunisia). Although we found a low level of agricultural production diversity and a fairly diversified diet among women, we observed a systematic weak positive association between five different indicators of agricultural production diversity and women's dietary diversity. We observed a stronger positive association between women's dietary diversity and women being more educated and households being wealthier. Neither diversity of food supplies in food markets nor market distance were associated with women's dietary diversity, whereas we observed a higher level of consumption of some products (dairy) when they were produced on the farm.

Because the effectiveness of a coronavirus disease lockdown in curbing coronavirus disease spread depends on public support, acquiring real-time information about the way populations reacted to the lockdown is crucial. In France, such public support remained fragile among low-income persons, probably because the lockdown exacerbated preexisting social inequalities and conflicts.

IntroductionWith France one of the European countries most strongly affected by COVID-19 in the spring of 2020, French authorities imposed a nationwide lockdown for 8 weeks (March 17-May 10). This study explored the perception of the adult population about the need for-and access to-psychological support from health care professionals (HCP) in response to concerns about the psychological needs during lockdown.Material and methodThis online cross-sectional survey of a representative sample of the adult general population of mainland France (N = 2,003) took place during the last four days of the French lockdown (May 7-10, 2020).ResultsOne in eight respondents (12.2%) perceived a need for psychological support from an HCP during the lockdown; most had symptoms of depression and/or anxiety of at least moderate intensity. Only a third (29.8%, 3.6% of the entire sample) actually obtained this support. Factors associated with this perceived need included: age under 35, economic difficulties due to lockdown, pre-lockdown use of psychological support, infection with COVID-19, serious worries about becoming infected, and heavy media use to obtain information about the disease. Among those who perceived a need for psychological support, the elderly were the most likely not to consult an HCP. People aged 35-64, those with high income, and those seriously worried about developing COVID-19 were the most likely to forgo seeking access to care because of their fear of infection by the coronavirus-2019.ConclusionThe perceived need for psychological support from an HCP and access to it appeared to be strongly associated with COVID-19 exposure factor. More research about this association is needed to improve the health authorities' understanding of the population's psychological needs in this situation and to enhance HCPs' abilities to meet them. In particular, further research of its specific impact on youth is necessary.

Angiosperm cell adhesion is dependent on interactions between pectin polysaccharides which make up a significant portion of the plant cell wall. Cell adhesion in Arabidopsis may also be regulated through a pectin-related signaling cascade mediated by a putative O-fucosyltransferase ESMERALDA1 (ESMD1), and the Epidermal Growth Factor (EGF) domains of the pectin binding Wall associated Kinases (WAKs) are a primary candidate substrate for ESMD1 activity. Genetic interactions between WAKs and ESMD1 were examined using a dominant hyperactive allele of WAK2, WAK2cTAP, and a mutant of the putative O-fucosyltransferase ESMD1. WAK2cTAP expression results in a dwarf phenotype and activation of the stress response and reactive oxygen species (ROS) production, while esmd1 is a suppressor of a pectin deficiency induced loss of adhesion. Here we find that esmd1 suppresses the WAK2cTAP dwarf and stress response phenotype, including ROS accumulation and gene expression. Additional analysis suggests that mutations of the potential WAK EGF O-fucosylation site also abate the WAK2cTAP phenotype, yet only evidence for an N-linked but not O-linked sugar addition can be found. Moreover, a WAK locus deletion allele has no effect on the ability of esmd1 to suppress an adhesion deficiency, indicating WAKs and their modification are not a required component of the potential ESMD1 signaling mechanism involved in the control of cell adhesion. The WAK locus deletion does however affect the induction of ROS but not the transcriptional response induced by the elicitors Flagellin, Chitin and oligogalacturonides (OGs).

IntroductionOur objective was to assess whether clusters of centers with similar peritoneal dialysis (PD) catheter related practices were associated with differences in the risk of technique failure.MethodsPatients on incident PD in French centers contributing to the French Language PD Registry from 2012 to 2016 were included in a retrospective analysis of prospectively collected data. Centers with similar catheter cares practices were gathered in clusters in a hierarchical analysis. Clusters of centers associated with technique failure were evaluated using Cox and Fine and Gray models. A mixed effect Cox model was used to assess the influence of a center effect, as explained by the clusters.ResultsData from 2727 catheters placed in 64 centers in France were analyzed. Five clusters of centers were identified. After adjustment for patient-level characteristics, the fourth cluster was associated with a lower risk of technique failure (cause specific-HR 0.70, 95%CI 0.54-0.90. The variance of the center effect decreased by 5% after adjusting for patient characteristics and by 26% after adjusting for patient characteristics and clusters of centers in the mixed effect Cox model. Favorable outcomes were observed in clusters with a greater proportion of community hospitals, where catheters were placed via open surgery, first dressing done 6 to 15 days after catheter placement, and local prophylactic antibiotics was applied on exit-site.ConclusionSeveral patterns of PD catheter related practices have been identified in France, associated with differences in the risk of technique failure. Combinations of favorable practices are suggested in this study.

Antecedentes. La enfermedad crónica infantil tiene impacto en la familia y afecta al paciente física, psicoemocional y socialmente. La hipótesis de este estudio es que la identificación de tales factores puede servir para mejorar su formación y competencia comunicativa y, consecuentemente, la gestión de la enfermedad crónica. Objetivo. Identificar las necesidades formativas psicopedagógicas en pediatras y residentes en pediatría del mayor hospital público en las Islas Baleares, España. Materiales y métodos. Estudio de diseño mixto cuantitativo-cualitativo, donde 51 pediatras y residentes —71.8% del servicio— contestaron un cuestionario y 26 participaron en entrevistas analizadas con análisis de contenido. Resultados. Los pediatras consideran que el apoyo y la cohesión familiar son los factores más relevantes para gestionar adecuadamente una enfermedad crónica infantil, pero manifiestan tener escasos conocimientos sobre el desarrollo emocional y psicológico de los niños y adolescentes. Destacan la escasa comunicación entre pediatras y escuela, así como la deficiente información sobre servicios socioeducativos que se ofrecen en el hospital y también en la comunidad. Los resultados cualitativos fueron organizados en cinco bloques temáticos: impacto de la enfermedad crónica infantil en la familia, formación psicopedagógica de los pediatras, dificultades en la práctica, comunicación entre escuela y hospital y el hospital como entidad educativa. Conclusión. La pediatría hospitalaria requiere considerar las específicas necesidades psicoemocionales de la familia y del menor, para lo cual se necesita formación psicopedagógica, así como un trabajo interprofesional entre sanitarios y educadores.

The objectives of this paper are to highlight the benefits of sharing information to Western Pacific Region Member States and to identify similarities at the regional level in terms of food safety issues and public health protection. In addition, it aims to propose an improved partnership among regional food safety authorities and WHO on targeted objectives.

BackgroundExisting diet quality indices often show theoretical and methodological limitations, especially with regard to validation.ObjectiveTo develop a diet quality index based on the probability of adequate nutrient intake (PANDiet) and evaluate its validity using data from French and US populations.Material and methodsThe PANDiet is composed of adequacy probabilities for 24 nutrients grouped into two sub-scores. The relationship between the PANDiet score and energy intake were investigated. We evaluated the construct validity of the index by comparing scores for population sub-groups with 'a priori' differences in diet quality, according to smoking status, energy density, food intakes, plasma folate and carotenoid concentrations. French and US implementations of the PANDiet were developed and evaluated using national nutritional recommendations and dietary surveys.ResultsThe PANDiet was not correlated with energy for the French implementation (r = -0.02, P>0.05) and correlated at a low level for the US implementation (r = -0.11, PConclusionsThe PANDiet provides a single score that measures the adequacy of nutrient intake and reflects diet quality. This index is adaptable for use in different countries and relevant at the individual and population levels.

BackgroundEuvolemia is an important adequacy parameter in peritoneal dialysis (PD) patients. However, accurate tools to evaluate volume status in clinical practice and data on volume status in PD patients as compared to healthy population, and the associated factors, have not been available so far.MethodsWe used a bio-impedance spectroscopy device, the Body Composition Monitor (BCM) to assess volume status in a cross-sectional cohort of prevalent PD patients in different European countries. The results were compared to an age and gender matched healthy population.ResultsOnly 40% out of 639 patients from 28 centres in 6 countries were normovolemic. Severe fluid overload was present in 25.2%. There was a wide scatter in the relation between blood pressure and volume status. In a multivariate analysis in the subgroup of patients from countries with unrestricted availability of all PD modalities and fluid types, older age, male gender, lower serum albumin, lower BMI, diabetes, higher systolic blood pressure, and use of at least one exchange per day with the highest hypertonic glucose were associated with higher relative tissue hydration. Neither urinary output nor ultrafiltration, PD fluid type or PD modality were retained in the model (total R² of the model = 0.57).ConclusionsThe EuroBCM study demonstrates some interesting issues regarding volume status in PD. As in HD patients, hypervolemia is a frequent condition in PD patients and blood pressure can be a misleading clinical tool to evaluate volume status. To monitor fluid balance, not only fluid output but also dietary input should be considered. Close monitoring of volume status, a correct dialysis prescription adapted to the needs of the patient and dietary measures seem to be warranted to avoid hypervolemia.