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A first-in-human Phase 1 study of LOXO-338, an oral selective Bcl-2 inhibitor, in patients with advanced hematologic malignancies
No full textInternational audienc
Vers une microbiologie durable : enquête sur l'engagement écoresponsable des microbiologistes français
No full textInternational audienceBiologists are committed to an eco-responsible approach in their professional activity and the operation of their laboratory(ies). The French Society of Microbiology (SFM) has created a group of persons involved in the corporate social responsibility (CSR) of their society. One of the first steps was to ask about their commitment and habits in this field. A questionnaire is sent by email to the 1500 members of the SFM. Twenty percent responded to the 40 questions that address each person's knowledge on the subject, travel habits, laboratory operation (purchases, waste…), personal and collective commitment. Many initiatives are thus listed in these different areas. Microbiologists can draw inspiration from them to change their habits in their own laboratories with a felt need to strengthen support structures and institutionalize eco-responsible approaches.A network of dedicated microbiologists will enable us to explore avenues for improvement and sharing of good practices.Les biologistes s'engagent dans une démarche écoresponsable dans leur activité professionnelle et le fonctionnement de leurs laboratoires. La Société française de microbiologie (SFM) a créé un groupe de personnes souhaitant s'impliquer dans la responsabilité sociétale et sociale (RSE) de leur société. Une des premières démarches entreprises consiste à faire le bilan de l'engagement des microbiologistes dans ce domaine.Un questionnaire a été envoyé par messagerie aux 1500 membres de la SFM. 20 % d'entre eux ont répondu aux 40 questions qui abordent les connaissances de chacun sur le sujet, les habitudes de déplacement, le fonctionnement du laboratoire (achats, déchets, informatique), l'engagement personnel et collectif.De nombreuses initiatives ont ainsi été listées dans ces différents domaines. Les microbiologistes peuvent s'en inspirer pour modifier leurs habitudes dans leurs propres laboratoires, avec une nécessité ressentie de devoir renforcer le soutien aux structures et d'institutionnaliser les démarches écoresponsables. Un réseau de microbiologistes investis permettra d'explorer des voies d'amélioration et de partage des bonnes pratiques
Clues to Revising the Conventional Diagnostic Algorithm for Endometriosis
No full textInternational audienceEndometriosis is a complex gynecologic disorder characterized primarily by symptoms of pelvic pain, infertility, and altered quality of life. National and international guidelines highlight the diagnostic difficulties and lack of conclusive diagnostic tools for endometriosis. Furthermore, guidelines are becoming questionable at an increasingly rapid rate as new diagnostic techniques emerge. This work aims to provide a knowledge synthesis of the relevance of various diagnostic tools and to assess areas of improvement of conventional algorithms. MEDLINE and Cochrane Library databases were searched from January 2021 to December 2023 using relevant key words. Articles evaluating the diagnostic relevance and performance of various tools were included and independently reviewed by the authors for eligibility. Included studies were assessed using the GRADE and QUADAS-2 tools. Of the 4204 retrieved articles, 26 were included. While anamnesis and clinical examination do contribute to diagnostic accuracy, their level of evidence and impact on the diagnostic process remains limited. Although imaging techniques are recommended to investigate endometriosis, ultrasonography remains highly operator dependent. Magnetic resonance imaging appears to exhibit higher sensitivities than ultrasound. However, concerns persist with regards to the terminology, anatomical definition of lesions, and accuracies of both ultrasound and magnetic resonance imaging. Recently, several biological markers have been studied and cumulative evidence supports the contribution of noncoding RNAs to the diagnosis of endometriosis. Marginal improvements have been suggested for anamnesis, clinical examination, and imaging examinations. Conversely, some biomarkers, including the saliva microRNA signature for endometriosis, have emerged as diagnostic tools which inspire reflection on the revision of conventional diagnostic algorithms
Intravenous administration of antibiotics by prolonged and continuous infusion
No full textInternational audienceHighlightsProlonged or continuous infusions may improve the ease of administration and/or clinical effectiveness in some situations.Antibiotics, in particular beta-lactam antibiotics, are unstable molecules, their infusion modes must be strictly controlled.These guidelines, based on a literature review, suggest practical methods of administration in hospitals and outpatient care.</ul
Gadolinium leakage into ocular structures as a marker in stroke: A retrospective analysis of the WAKE-UP trial
No full textInternational audienceIntroduction: Blood-brain barrier disruption in acute ischemic stroke is a well described phenomenon associated with hemorrhagic complications. The hyperintense acute reperfusion marker (HARM) represents gadolinium leakage in the cerebrospinal fluid. Gadolinium leakage into ocular structures (GLOS) might represent a dysfunction of the blood-ocular barrier. We aimed to investigate the presence of GLOS in the WAKE-UP trial and its association with HARM, hemorrhagic transformation (HT) and functional outcome.Patients and methods: Randomized patients from the WAKE-UP trial who underwent dynamic susceptibility contrast perfusion weighted imaging at baseline and fluid attenuated inversion recovery (FLAIR) imaging at both baseline and follow-up, were included. We studied the association between GLOS with baseline and outcome variables.Results: We were able to analyze the data of 192/503 (38%) randomized WAKE-UP patients. GLOS was detected in 56 (29%) cases, four times more frequently than HARM (7%). GLOS positive patients were older (73 vs 65 years; p < 0.01), had a lower glomerular infiltration rate (GFR 79.5 vs 87.2 mL/min; p = 0.01), higher white matter hyperintensity volume (15.0 vs 9.9 mL; p < 0.01), less often presented with a large vessel occlusion (27% vs 44%; p = 0.02) and HARM was more often observed (9/56 vs 4/136; p = 0.01). In multivariable analysis the presence of GLOS was not associated with HT nor poor functional outcome (modified Rankin scale 3-6).Discussion and conclusion: GLOS is a relatively common finding in acute ischemic stroke patients and is associated with older age, worse renal function, increased white matter hyperintensity burden and HARM but not with HT or functional outcome
Variabilities in both Modified Ashworth Scale scores and biomechanical parameters among different physiotherapists when assessing lower limb spasticity
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Behavioural, biochemical and functional phenotyping of subchronic exposure to chlordecone in mice
No full textInternational audienceBackground: Chlordecone (CLD) is a persistent organochlorine pesticide formerly used against banana weevil. It is detectable in blood samples from a large proportion of the population in the French Caribbean Islands. Several experimental studies have demonstrated acute neurotoxicity of CLD, but the effects of a subchronic exposure to CLD remains to be studied.Methods: Young adult male mice were injected intraperitoneally with 3 mg/kg CLD (n = 34) or vehicle (n = 22), twice a week, for eight weeks. Behavior, regional brain accumulation, and effects on the dopaminergic system were studied. In addition, functional ultrasound imaging (fUSi) was used to probe the visual, somatosensory and dopaminergic pathways.Results: CLD was detected in all brain regions (5-15 mg/kg) after two-month exposure, without any marked impact on behavior (anxiety, motor coordination, memory). The dopaminergic system was mostly unaffected, despite slight decreases in the number of TH-positive neurons and the expression of VMAT2, quantified in a subset of animals. fUSi highlighted a decreased response to the visual stimulation in CLD-exposed animals, in contrast to the sensorimotor response, which was found unaltered.Conclusion: The two-month-long, systemic, exposure to an intermediate dose of CLD resulted in a mostly unaffected phenotype, with a normal behavior and a largely intact dopaminergic system. Interestingly, functional ultrasound imaging was able to detect an altered visual response. This study position functional ultrasound imaging as a promising technique to capture early signs of neurotoxicity, opening up opportunities for "toxico-fUS" in the field of neurotoxicology
Reply to Letter to the Editor: "Silent myocardial infarction fatty scars detected by coronary calcium score CT scan in diabetic patients without a history of coronary heart disease"
No full textInternational audienceNo abstract availabl
Un flux de travail guidé par l'IA pour une accélération de l'optimisation d'un système acellulaire de synthèse de protéines
No full textInternational audienceCell-free protein synthesis (CFPS) is a versatile tool for rapid biological prototyping. However, exploring the large number of component combinations is a very time-consuming process. Active learning (AL) is known to reduce the number of experiments required, but is rarely integrated into routine laboratory workflows. To address this, we developed a fully automated Design-Build-Test-Learn (DBTL) pipeline that streamlines this optimization process with an improved AL strategy that selects informative and diverse experimental conditions. The Design phase was created entirely using ChatGPT-4 without manual code revisions, dramatically reducing coding time. This pipeline was implemented in a modular way within the Galaxy platform, following the Findable-Accessible-Interoperable-Reusable (FAIR) principles. When applied to the optimization of colicin M and E1 in both Escherichia coli and HeLa-based CFPS systems, a 2- to 9-fold increase in yield was achieved in just four cycles. This framework enables reliable, automated workflows for routine synthetic biology
Impact of organized and opportunistic screening on excess mortality and on social inequalities in breast cancer survival
No full textInstitut National du Cancer (INCa) Santé Publique France (SpF)International audienceIn most developed countries, both organized screening (OrgS) and opportunistic screening (OppS) coexist. The literature has extensively covered the impact of organized screening on women's survival after breast cancer. However, the impact of opportunistic screening has been less frequently described due to the challenge of identifying the target population. The aim of this study was to describe the net survival and excess mortality hazard (EMH) in each screening group (OrgS, OppS, or No screening) and to determine whether there is an identical social gradient in each groups. Three data sources (cancer registry, screening coordination centers, and National Health Data System [NHDS]) were used to identify the three screening groups. The European Deprivation Index (EDI) defined the level of deprivation. We modeled excess breast cancer mortality hazard and net survival using penalized flexible models. We observed a higher EMH for “No screening” women compared with the other two groups, regardless of level of deprivation and age at diagnosis. A social gradient appeared for each group at different follow‐up times and particularly between 2 and 3 years of follow‐up for “OrgS” and “OppS” women. Net survival was higher for “OrgS” women than “OppS” women, especially for the oldest women, and regardless of the deprivation level. This study provides new evidence of the impact of OrgS on net survival and excess mortality hazard after breast cancer, compared with opportunistic screening or no screening, and tends to show that OrgS attenuates the social gradient effect