Laboratoire National de Santé

BackgroundThe preferred timing of treatment of nonculprit lesions in patients with ST-segment elevation myocardial infarction (STEMI) remains uncertain. A comparison of immediate percutaneous coronary intervention (PCI) guided by instantaneous wave-free ratio (iFR) and deferred PCI guided by cardiac stress magnetic resonance imaging (MRI) in patients with STEMI and multivessel disease is warranted.MethodsIn this international, investigator-initiated, open-label, randomized, controlled trial, patients with STEMI and at least one nonculprit lesion who had undergone successful primary PCI were randomly assigned in a 1:1 ratio to immediate iFR-guided PCI (in lesions with >50% stenosis and an iFR of ≤0.89 [normal value, >0.89]) or deferred cardiac stress MRI–guided PCI within 6 weeks after randomization. The primary end point was a composite of death from any cause, recurrent myocardial infarction, or hospitalization for heart failure at 3-year follow-up.ResultsThe trial included 1146 patients (558 in the iFR group and 588 in the MRI group) with a mean (±SD) age of 63±11 years; 78% were men. A total of 237 of 556 patients (42.6%) in the iFR group and 110 of 587 patients (18.7%) in the MRI group underwent nonculprit-lesion coronary-artery PCI. A primary-end-point event occurred in 50 patients (9.3%) in the iFR group and in 55 patients (9.8%) in the MRI group (hazard ratio, 0.95; 95% confidence interval, 0.65 to 1.40; P=0.81). Serious adverse events occurred in 145 patients in the iFR group and in 181 in the MRI group.ConclusionsAmong patients with STEMI who have undergone successful primary PCI, immediate iFR-guided PCI was not superior to deferred cardiac stress MRI–guided PCI of nonculprit coronary-artery lesions with respect to death from any cause, recurrent myocardial infarction, or hospitalization for heart failure at 3 years. (Funded by Philips Volcano and others; iMODERN ClinicalTrials.gov number, NCT03298659.)

Notifications of Salmonella Strathcona infections increased in Europe in 2023 prompting a multi-country outbreak investigation. We aimed to describe the epidemiology of S. Strathcona infections in 17 European countries 2011–2024, investigate the genetic relatedness of S. Strathcona isolates and identify the vehicle. Cases were persons residing in the study area and with a laboratory-confirmed S. Strathcona infection 2011–2024. Confirmed cases had a S. Strathcona isolate clustering with the outbreak reference strain in core genome multilocus sequence typing (cgMLST) within 7 allelic differences (AD) and possible cases within 8–13 AD. Probable cases had an epidemiological link to a confirmed case and non-outbreak cases had an isolate > 13 AD from the outbreak reference strain. Since 2011, 662 S. Strathcona infections have been identified: 469 confirmed, 161 probable, 13 possible and 19 non-outbreak cases. Median age of the cases was 34 years (IQR: 19–58 years) and 306 (47.5%) were notified in 2023–2024. Most sequenced isolates (469/496; 94.5%) were highly genetically related (≤ 7 AD) over time and across countries, compatible with a common source. Epidemiological and traceback investigations identified small tomatoes from Sicily as the suspect food vehicle. Stringent control measures at the source are needed to stop the contamination and prevent future cases.

Background/Objectives: Triosephosphate Isomerase (TPI) is a glycolytic enzyme known to be associated with TPI deficiency, a severe form of childhood-onset glycolytic enzymopathy associated with hemolytic anemia, neuromuscular impairment and early death. Most often the disease results from the common TPI1E105D mutation, which can be either homozygous or compound heterozygous with another allele. Methods: We purified TPIR5G protein, studied mutant protein biochemistry, established and characterized TPIR5G/f.s.patient cells, and investigated newly identified compounds for their efficacy in vitro using Western blot and TPI activity assays. Results: We identified novel TPI1 alleles that result in TPI Deficiency with an atypical presentation lacking anemia and with more slowly developing neurologic and locomotor impairment. The patient was found to be compound heterozygous with a missense mutation resulting in an R5G amino acid substitution and a frameshift mutation that is a predicted null allele. To better understand disease pathogenesis in this patient, we expressed and purified the TPIR5G human protein and studied it biochemically in addition to studying TPIR5G/f.s.patient cells. We discovered that purified TPIR5G protein has wildtype activity with modestly increased dimer stability. We also discovered that steady-state TPI protein levels were markedly reduced, suggesting that the instability of the mutant protein underlies disease pathogenesis. We tested compounds recently identified in a screen for novel TPI Df therapies for their efficacy in TPIR5G/f.s.patient cells. All three compounds significantly increased TPI protein levels in patient cells. As expected, since the mutant protein retains essentially wild type activity, the increase in TPI protein levels also resulted in a significant increase in TPI activity. Conclusions: These results establish TPIR5G as a TPI Df allele, demonstrate that reduced stability of the mutant protein underlies pathogenesis akin to other disease-causing alleles, and suggest that recently discovered developing therapies will likely function broadly and should be developed as potential TPI Df therapies.

Processing of electronic waste (e-waste) causes the release of toxic substances which may lead to occupational exposure. The study aimed to gather information on potential occupational exposure during e-waste recycling, with a focus on biomonitoring of chromium, cadmium, mercury and lead. In eight European countries, 195 workers involved in the recycling of lead batteries, white goods, brown goods and metals and plastics were studied. These workers were compared to 73 controls with no direct involvement of e-waste recycling or other metal processing activities. The samples collected consisted of urine, blood and hair samples, along with personal air samples, hand wipes, settled dust samples and contextual information. Chromium, cadmium, mercury and lead was measured in urine, hair, air samples, hand wipes and settled dust; cadmium and lead in whole blood and chromium in red blood cells. Results showed that lead exposure is of concern, with workers from all five types of e-waste showing exposure, with elevated measurements in all matrices. Internal exposure markers were positively correlated with markers of external exposure, indicating workers are not adequately protected. Exposure to mercury and cadmium was also observed but to a much lesser extent with raised cadmium concentrations in urine and blood of all workers when compared to controls and raised mercury concentrations were found in brown goods workers when compared to controls. This study has highlighted exposure concerns when processing e-waste, particularly for lead across all waste categories studied, indicating a need for improved control measures in this sector.

The Gurson–Tvergaard–Needleman GTN model is widely used for ductile fracture simulations. However, the selection of its parameters is often done randomly to reproduce the experimental data without considering the physical consistency of the set of parameters selected. This contribution is dedicated to the relevance of the GTN model parameters selection using a consistent method based on the ductile fracture phenomenology. The proposed method consists of the prioritization of the void volume fraction parameters in accordance with the kinetics of the ductile fracture phenomenon, while the nucleation and fracture parameters are chosen in conformity to the strength to fracture. Experimental data obtained from 12NC6 steel is used through various tests. Axisymmetric notched and compact tension specimens are used. The interest of the use of this variety of tests lies in the variation of stress triaxiality ratio given its widely proven importance in the ductile fracture process. The strategy is finally applied to a CT (Compact-Tension) test simulation. Satisfactory result are achieved while the number of attempts to reproduce the experimental data is considerably reduced, this lead to considerable saving of computational time.

Pesticides are compounds of major use in agriculture worldwide. Nevertheless, many pesticide chemicals are classified as endocrine disruptors and potentially carcinogens. Farmers and farmworkers are particularly exposed and are at high risk of developing health-related impairments. In Morocco, the lack of awareness towards pesticide hazards and the inappropriate application of safety measures might increase the exposure as well as the risks of health concerns. In this paper, we present the framework of a study designed to assess pesticide exposure among Moroccan farmers and farmworkers and to evaluate potential health effects, namely endocrine and epigenetic impacts. Human biological monitoring will be conducted to determine pesticide levels in urine following the development and validation of sensitive chromatography methods (SPE, UPLC-MS/MS). Biomarkers of exposure include a set of parent and metabolite pesticide compounds (organophosphates, pyrethroids, triazines and urea-based pesticides). Thyroid and reproductive hormones (TSH, T3, T4, FSH and LH) as well as global and specific DNA methylation markers (5-mC, 5-hmC, N6-mA, THRB and LHR) are selected as biomarkers of effects. This provides guiding steps and methods to perform reliable exposure evaluation and health impact assessment. This study aims to expand the current knowledge on the endocrine and epigenetic risks related to pesticides, especially in low- and middle-income countries.

ABSTRACTForensic epidemiology (FE) is a multi‐disciplinary field that applies epidemiologic principles and methods to collate and analyze trends and associations among medical and scientific examinations of adverse health outcomes with criminal or other legal implications. FE has been applied to a range of issues including bioterrorism, mass casualty events, and occupational hazards to inform public health and legal responses. This review explores the historical evolution, primary methodologies, and most common contemporary applications of FE, emphasizing the contribution of forensic medicine and science to public health and safety. Key methods such as descriptive and analytical epidemiology, biostatistical analyses, and field investigations are discussed, highlighting their application in bioterrorism responses, toxicological investigations, death inquiries, and public health policy development. The review underscores the strengths of FE, including its objective, evidence‐based framework and multi‐disciplinary collaboration, while addressing challenges like data limitations, ethical considerations, and the complexity of demonstrating causation in legal contexts. By applying epidemiologic principles and methods to analyze the findings from forensic investigations, FE not only supports the resolution of individual health‐related legal disputes but also has applications at the population level for public health interventions. These findings demonstrate the growing importance of FE as a vital tool in addressing the complexities of modern forensic and public health challenges.

E-waste contains hazardous chemicals that may be a direct health risk for workers involved in recycling. We conducted an untargeted metabolomics analysis of urine samples collected from male e-waste processing workers to explore metabolic changes associated with chemical exposures in e-waste recycling in Belgium, Finland, Latvia, Luxembourg, the Netherlands, Poland, and Portugal. Questionnaire data and urine samples were obtained from workers involved in the processing of e-waste (sorting, dismantling, shredding, pre-processing, metal, and non-metal processing), as well as from controls with no known occupational exposure. Pre- and post-shift urine samples were collected and analysed using ultrahigh-performance liquid chromatography-mass spectrometry (UPLC-MS). A total of 32 endogenous urinary metabolites were annotated with a Variable Importance in Projection (VIP) above 2, indicating that e-waste recycling is mainly associated with changes in steroid hormone and neurotransmitter metabolism, energy metabolism, bile acid biosynthesis, and inflammation. The highest VIP was observed for dopamine-o-quinone, which is linked to Parkinson's disease. These and other changes in metabolism in workers employed in the processing of e-waste need further verification in targeted studies.