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First evidence of deleterious effect of pesticide mixture on health status in semi-captive grey partridges
No full textInternational audiencePesticides are mainly used in agroecosystems to control pests. Due to their limited specificity, the resulting widespread contamination may cause unintended effects on non-target organisms that use these habitats. While increasing attention is paid to the relationship between single substances and phenotype on non-target species, their combined impacts are still largely unknown. Since interactions between pesticides may also impact organisms' health, studying them as complex mixtures is the more realistic approach. Here, we present the first experimental study testing the relationship between an environmentally relevant pesticide mixture and health biomarkers on a farmland avian non-target model. To do so, we used 40 semi-captive grey partridges (Perdix perdix) fed for five months with conventional grains. Their plant protection product (PPP) load (i.e., the number of PPPs, the total sum of scaled pesticide concentrations and the total toxicity index) in blood and proxies of health status (evaluated using behavioral and physiological features) were monitored at the end of the exposure period. We demonstrated, for the first time, concerning correlations between PPP load indexes and bird healthrelated features (physical activity, flight initiation distance, eye ring redness and acetylcholinesterase activity). Overall, we highlighted the urgent need to consider environmentally-relevant PPP mixture when biomonitoring non-target vertebrates in ecotoxicological studies.</div
Long-term outcome following liver transplantation of patients with ACLF grade 3
No full textInternational audienceBackground and aims: Utility, a major principle for allocation in the context of transplantation, is questioned in patients with acute-on chronic liver failure grade 3 (ACLF-3) who undergo liver transplantation (LT). We aimed to explore long-term outcomes of patients included the three-center retrospective French experience published in 2017.Method: All patients with ACLF-3 (n=73) as well as their transplanted matched controlled with ACLF-2 (n=145), 1 (n=119) and no ACLF (n=292) that have participated in the princeps study published in 2017 were included. We explored 5- and 10-year patient and graft survivals, causes of death and their predictive factors.Results: Median follow-up of patients ACLF-3 patients was 7.5 years. At LT, median MELD was 40. In patients with ACLF-3, 2, 1 and no ACLF, 5-year patients' survivals were respectively 72.6% vs. 69.7% vs. 76.4% vs. 77.0% (p=0.31). Ten-year patients' survival ACLF-3 was 56.8% and was not different other groups (p=0.37) Leading causes of death in ACLF-3 patients were infections (33.3%), and cardiovascular events (23.3%). After exclusion of early death, UCLA futility risk score, age-adjusted Charlson comorbidity index and Chronic Liver Failure Consortium ACLF score were independently associated with 10-year patients' survival. Long-term grafts' survivals were not different across the groups. Clinical frailty scale and WHO performance status improved over time in patients alive after 5 years.Conclusion: 5- and 10-year patients' and grafts' survivals in ACLF-3 patients were not different from their controls. 5-year patients' survival is higher than that of the 50%-70% threshold defining the utility of liver graft. Efforts should focus on candidates' selection based on comorbidities as well as the prevention of infection and cardiovascular events standing as the main cause of death.Impact and implications: While short-term outcomes following liver transplantation in the most severely ill cirrhotic patients (ACLF-3) are known, long-term data are limited, raising questions about the utility of graft allocation in the context of scarce medical resources. This study provides a favorable long-term update, confirming no differences in 5- and 10-year patient and graft survival following liver transplantation in ACLF-3 patients compared to matched ACLF-2, ACLF-1, and no-ACLF patients. The study highlights the risk of dying from infection and cardiovascular causes in the long-term and identifies scores including comorbidities evaluation, such as the age-adjusted Charlson Comorbidity Index, as independently associated with long-term survival. Therefore, physicians should consider the cumulative burden of comorbidities when deciding to transplant these patients. Additionally, after transplantation, the study encourages mitigating infectious risk with tailored immunosuppressive regimens and managing tightly cardiovascular risk over time
Women for Quantum -- Manifesto of Values
No full textInternational audienceData show that the presence of women in quantum science is affected by a number of detriments and their percentage decreases even further for higher positions. Beyond data, from our shared personal experiences as female tenured quantum physics professors, we believe that the current model of scientific leadership, funding, and authority fails to represent many of us. It is time for a real change that calls for a different kind of force and for the participation of everyone. Women for quantum calls for a joint effort and aims with this initiative to contribute to such a transformation
Point contact-restricted cAMP signaling control ephrin-A5-induced axon repulsion
No full textInternational audienceSignal transduction downstream of axon guidance molecules is essential to steer developing axons. Second messengers including cAMP are key molecules shared by a multitude of signaling pathways and are required for a wide range of cellular processes including axon pathfinding. Yet, how these signaling molecules achieve specificity for each of their downstream pathways remains elusive. Subcellular compartmentation emerged as a flexible strategy to reach such a specificity. Here, we show that point contact-restricted cAMP signals control ephrin-A5-evoked axon repulsion in vitro by modulating Focal Adhesion Kinase phosphorylation and the assembly and disassembly rate of point contacts. Consistently, preventing point contact-specific cAMP signals, in developing retinal ganglion cells in vivo alters the refinement of their terminal axonal arbor in the brain. Altogether, our study identifies point contacts as a compartment containing a local cAMP signal required for ephrin-A5dependent axon guidance and highlights the crucial role of such subcellularly restricted second messenger signals in the wiring of neuronal circuits.</div
Organisation of clinical research in intensive care units: A scoping review
No full textInternational audienceBackground: Clinical research is essential for the development and progress of therapies and procedures. Intensive care units (ICUs) manage the sickest patients. Numerous clinical trials are organised in ICUs to evaluate new treatments or support techniques. Concomitantly, new professions involved in clinical research set-ups are emerging.Aim: The aim of this scoping review was to identify the nature and extent of research evidence on the organisation of clinical research in ICUs.Methods: This review focusses on observational and qualitative narrative studies dealing with clinical research organisation in ICUs, with a special interest in structures coordinating research, the roles of clinical research professionals, and the training required. Medline and Embase were analysed between January 2000 and June 2024. Assessment of the study quality was based on the Let Evidence Guide Every New Decision evaluation system and the Newcastle-Ottawa quality assessment scale.Results: Of the 14 studies reviewed, four were narrative and 10 observational descriptive. All were based on cross-sectional surveys. Most studies were carried out in North America, the United Kingdom, and Australia/New Zealand. ICU clinical research professionals were mostly female nurses aged between 31 and 50 years who had a wide diversity of training profiles and performed greatly varied tasks from data collection to publication of the article. Reported job satisfaction depended on the degree of autonomy, the workload, the extent of professional recognition, and opportunities for professional promotion.Conclusions: The organisation of ICU clinical research reflects considerable diversity in training, tasks, job organisation, and responsibilities
Unveiling the potential abuse liability of α-D2PV: A novel α-carbon phenyl-substituted synthetic cathinone
No full textInternational audienceSynthetic cathinones are emerging psychoactive substances designed to mimic the effects of classical psychostimulants. Among them, α-D2PV, a novel pyrrolidine-containing cathinone characterized by a phenyl group on the α-carbon atom, has gained significant attention. This study investigates the in vitro and in silico mechanism of action as well as the abuse liability of α-D2PV using rodent models. Dopamine (DA), noradrenaline (NE), and serotonin (5-HT) uptake inhibition assays were conducted in HEK293 cells expressing the corresponding human monoamine transporter, complemented by molecular docking studies at the DA transporter (DAT). Behavioral studies in male Swiss CD-1 mice assessed locomotor activity and conditioned place preference, while microdialysis and self-administration experiments were performed in male Sprague-Dawley rats. The findings reveal that α-D2PV is a potent DA and NE uptake inhibitor, with minimal activity at the 5-HT transporter (SERT). Docking studies showed that the benzene rings of α-PVP and α-D2PV align precisely in their most stable conformations at DAT. In vivo, α-D2PV elicited dose-dependent hyperlocomotion, thigmotaxis, and rewarding effects in mice, alongside increased extracellular DA levels in the nucleus accumbens of awake rats. Self-administration experiments confirmed α-D2PV's high reinforcing efficacy, indicating a significant risk of abuse in humans. Finally, these results underscore the necessity for continued surveillance of α-D2PV within the illicit drug market. Furthermore, novel synthetic cathinones incorporating a phenyl ring at the α-carbon side chain warrant proactive monitoring due to their potential to retain dopaminergic activity and evade initial legal controls
Potassium management and heart failure: a nephrologist's perspective
No full textInternational audienceNo abstract availabl
Temporary Transvenous Pacing Performed in the Intensive Care Unit or in the Catheterization Laboratory
No full textInternational audienceABSTRACT Background Temporary transvenous pacing (TTP) is a common procedure, predominantly performed in the catheterization laboratory (cath lab) because of presumed lower complication rate. This study aims to evaluate the efficacy and safety of TTP placement in the ICU compared to TTP placement in the cath lab. Methods This retrospective, real‐life study included all patients requiring TTP in a tertiary care ICU between 2019 and 2022. Patients’ characteristics, TTP‐related data, outcomes, and complications were compared between groups (ICU vs. cath lab). Results Data from 193 patients receiving TTP were analyzed; 68.4% received TTP in the ICU and 31.6% in the cath lab. The main indication was atrioventricular block in 154 patients (79.8%). The operator was less frequently an interventional cardiologist in the ICU (12.1%) compared to the cath lab (100%, p < 0.001). TTP in the ICU was more frequently performed using a jugular access (72.0% vs. 1.6%), a right‐sided laterality (88.7% vs. 43.6%), and a balloon‐tipped catheter (100% vs. 0%, p < 0.001 for all comparisons). Success was 100% in both groups. The overall complication rate was 16.6%, with no significant difference between both groups (14.4% ICU vs. 21.3% cath lab, p = 0.13), but a tendency toward higher complications in the cath lab group (especially tamponade, lead displacement, and CIED infection). Conclusion In a daily clinical scenario, TTP placement appears as safe in the ICU than in the cath lab, regardless of the operator's level of expertise when performed in accordance with best practices. Nevertheless, TTP complications remain high, and alternatives should be used whenever possible
Mean arterial pressure is a major determinant of hypotension prediction index
No full textInternational audienceNo abstract availabl