Université de Poitiers
  • Poitiers, Poitou-Charentes, France
Recent publications
Background Recent multicenter studies identified COVID-19 as a risk factor for invasive pulmonary aspergillosis (IPA). However, no large multicenter study has compared the incidence of IPA between COVID-19 and influenza patients. Objectives To determine the incidence of putative IPA in critically ill SARS-CoV-2 patients, compared with influenza patients. Methods This study was a planned ancillary analysis of the coVAPid multicenter retrospective European cohort. Consecutive adult patients requiring invasive mechanical ventilation for > 48 h for SARS-CoV-2 pneumonia or influenza pneumonia were included. The 28-day cumulative incidence of putative IPA, based on Blot definition, was the primary outcome. IPA incidence was estimated using the Kalbfleisch and Prentice method, considering extubation (dead or alive) within 28 days as competing event. Results A total of 1047 patients were included (566 in the SARS-CoV-2 group and 481 in the influenza group). The incidence of putative IPA was lower in SARS-CoV-2 pneumonia group (14, 2.5%) than in influenza pneumonia group (29, 6%), adjusted cause-specific hazard ratio (cHR) 3.29 (95% CI 1.53–7.02, p = 0.0006). When putative IPA and Aspergillus respiratory tract colonization were combined, the incidence was also significantly lower in the SARS-CoV-2 group, as compared to influenza group (4.1% vs. 10.2%), adjusted cHR 3.21 (95% CI 1.88–5.46, p < 0.0001). In the whole study population, putative IPA was associated with significant increase in 28-day mortality rate, and length of ICU stay, compared with colonized patients, or those with no IPA or Aspergillus colonization. Conclusions Overall, the incidence of putative IPA was low. Its incidence was significantly lower in patients with SARS-CoV-2 pneumonia than in those with influenza pneumonia. Clinical trial registration The study was registered at ClinicalTrials.gov, number NCT04359693 .
Background Pregnancy and breastfeeding are associated with bone density loss. Fracture occurrence during pregnancy and post-partum, and its determinants, remain poorly known in Osteogenesis Imperfecta (OI). The aim of this study was to characterize fractures that occurred during pregnancy and post-partum in OI patients. Results We conducted a retrospective multicentric study including a total of 50 previously pregnant OI women from 10 Bone Centers in France. Among these patients, 12 (24%) patients experienced fractures during pregnancy or in the 6 months following delivery, and 38 (76%) did not experience any fracture. The most frequent localizations were: proximal femur (25%), spine (25%), distal femur (12.5%), and pelvis (12.5%). Fractures during pregnancy occurred during the third trimester and post-partum fractures occurred with a mean delay of 2 months following delivery. No fractures occurred during childbirth. We next compared the 12 patients with pregnancy or post-partum fractures with the 38 patients without fractures. Mean age at pregnancy was 32.7 ± 3.1 years-old in the fractured group, vs 29.3 ± 5.0 years-old in the non-fractured group ( p = 0.002). Breastfeeding was reported in 85.7% of patients in the fractured group, vs 47.1% in the non-fractured group ( p = 0.03). All patients with post-partum fractures were breastfeeding. Bone mineral density was significantly lower in patients with pregnancy-related fractures compared with other patients: spine Z-score − 2.9 ± 1.6DS vs − 1.5 ± 1.7DS ( p = 0.03), and total hip Z-score − 2.0 ± 0.7DS vs − 0.5 ± 1.4DS ( p = 0.04). At least one osteoporosis-inducing risk factor or disease other than OI was identified in 81.8% vs 58.6% of fractured vs non-fractured patients (not significant). Fracture during pregnancy or post-partum was not associated with the severity of OI. Bisphosphonates before pregnancy were reported in 16.7% and 21.1% of patients with pregnancy-related fractures and non-fractured patients, respectively (not significant). Conclusions OI management during pregnancy and post-partum should aim for optimal control of modifiable osteoporosis risk factors, particularly in patients with low BMD. Breastfeeding should be avoided.
Background Ethnicity might impact out-of-hospital cardiac arrest (OHCA) risk, but it has scarcely been studied in Europe. We aimed to assess whether ethnicity influenced the risk of OHCA of cardiac cause in Danish immigrants and its interplay with risk factors for OHCA and socioeconomic status. Methods This nationwide study included all immigrants between 18 and 80 years present in Denmark at some point between 2001 and 2020. Regions of origin were defined as Africa, Arabic countries, Asia, Eastern Europe, Latin America, and Western countries. OHCAs with presumed cardiac cause were identified from the Danish Cardiac Arrest Registry. Findings Overall, among 1,011,565 immigrants, a total of 1,801 (0.2%) OHCAs (median age 64 (Q1-Q3 53–72) years, 72% males) occurred. The age- and sex- standardized (reference: Western countries) incidence of OHCA (/1,00,000 person-years) was 34.6 (27.8–43.4) in African, 34.1 (30.4–38.4) in Arabic, 33.5 (29.3–38.2) in Asian, 35.6 (31.9–39.6) in Eastern European, and 16.2 (9.0–27.2) in Latin American immigrants. When selecting Western origin as a reference, and after adjusting on OHCA risk factors, Arabic (HR 1.18, 95%CI 1.04–1.35; P=0.01), Eastern European (HR 1.28, 95%CI 1.13–1.46; P<0.001), and African origin (HR 1.34, 95%CI 1.10–1.63; P<0.01) were associated with higher risk of OHCA, whereas Latin American origin (HR 0.58, 95%CI 0.35–0.0.96; P=0.03) was associated with lower risk of OHCA. Comparable results were observed when adjusting on education level and economic status. Interpretation This study emphasizes that ethnicity is associated with OHCA risk, even when considering traditional cardiac arrest risk factors. Funding R Garcia received a grant from the Fédération Française de Cardiologie for his post-doctoral fellowship and this work was supported by the Novo Nordisk Foundation Tandem Programme 2022 (grant# 31364).
Weathering transforms fresh un-weathered rock into saprolite and soils, porous materials that may hold available water for plants and nutrients. The conjoint characterization of mineral weathering and development of porosity is helpful in understanding rock weathering and the development of soil. The objective of this study was to investigate mineralogical transformations and the increase in total porosity during granodiorite weathering in South Brazil by combining petrographical observations, mineralogical analyses, and porosity measurements. The studied granodiorite profile presented a saprock of ∼2 m thickness with spheroidal weathering, a ∼15 m thick saprolite of and soil of ∼2 m thickness. The intensity of weathering was estimated using chemical indices (CIA and WIS) and by the production of fines particles of silt and clay sizes. As weathering increased from saprock to saprolite and soils total porosity increased from 1.73 % in the un-weathered rock, between 3.57 and 10.5 % in the saprock and 11.02 % in the saprolite. The chemical losses were limited in saprock and saprolite (CIA = 68, Δ4Si = 29.31 %) and increased in the topsoil (CIA = 85.73, Δ4Si = 56.83 %), indicating a moderate weathering intensity. Petrographic observations by optical microscope and SEM, chemical composition using SEM-EDS and X-ray diffraction results showed principal mineral weathering reactions were the transformations of biotite into vermiculite (with biotite/vermiculite mixed layers as intermediate weathering stages) and weathering of plagioclases and potassic felspars into kaolinite. The multi-mineral composition of the saprolite indicated a progressive transformation of primary minerals with increasing weathering intensity. The results show that the opening of the porosity is likely to control the development of the weathering and should deserve more detailed characterisation.
Objectives To identify the factors related to the presence of occult metastases before salvage total laryngectomy (STL) in rcN0 patients and to propose an algorithm to identify patients who do not require neck dissection (ND). Patients and methods This multicentric retrospective study included five centers with recruitment from 2008 to 2018. Inclusion criteria were: i) having been treated for laryngeal squamous cell carcinoma in first intention by radiotherapy (either alone or potentiated or preceded by induction chemotherapy), ii) having received STL with or without ND, iii) having an rcN0 neck at the time of STL. Results 120 patients met the inclusion criteria. The overall rate of occult metastases was 9.1 %. The rate was significantly higher in patients with an initial positive cN+ lymph node status (p < 0.005) and in advanced stages with rcT3-T4 lesions at recurrence (p < 0.005). Patients with occult metastases recurred earlier than those without (p = 0.002). The overall survival of patients was the same with or without ND (p = 0.16). There were significantly more healing complications requiring revision surgery in the group with ND than in the group without (p = 0.048). Conclusion ND does not confer a net survival benefit and is associated with significant complications. Patients without initial lymph node metastases who are rcT1-T2 at recurrence or rcT3-T4 with a recurrence period of more than 12 months could benefit from STL without ND. This decisional algorithm, which needs to be validated, would help avoid 58 % of ND procedures and their proven morbidity. Discipline Head and neck surgery.
Multimedia IoT (M-IoT) is an emerging type of Internet of things (IoT) relaying multimedia data (images, videos, audio and speech, etc.). The rapid growth of M-IoT devices enables the creation of a massive volume of multimedia data with different characteristics and requirements. With the development of artificial intelligence (AI), AI-based multimedia IoT systems have been recently designed and deployed for various video-based services for contemporary daily life, like video surveillance with high definition (HD) and ultra-high definition (UHD) and mobile multimedia streaming. These new services need higher video quality in order to meet the quality of experience (QoE) required by the users. Versatile video coding (VVC) is the new video coding standard that achieves significant coding efficiency over its predecessor high-efficiency video coding (HEVC). Moreover, VVC can achieve up to 30% BD rate savings compared to HEVC. Inspired by the rapid advancements in deep learning, we propose in this paper a wide-activated squeeze-and-excitation deep convolutional neural network (WSE-DCNN) technique-based video quality enhancement for VVC. Therefore, we replace the conventional in-loop filtering in VVC by the proposed WSE-DCNN model that eliminates the compression artifacts in order to improve visual quality and hence increase the end user QoE. The obtained results prove that the proposed in-loop filtering technique achieves \(-2.85\)%, \(-8.89\)%, and \(-10.05\)% BD rate reduction for luma and both chroma components under random access configuration. Compared to the traditional CNN-based filtering approaches, the proposed WSE-DCNN-based in-loop filtering framework achieves efficient performance in terms of RD cost.
Aims/hypothesis Diabetes has been recognised as a pejorative prognostic factor in coronavirus disease 2019 (COVID-19). Since diabetes is typically a disease of advanced age, it remains unclear whether diabetes remains a COVID-19 risk factor beyond advanced age and associated comorbidities. We designed a cohort study that considered age and comorbidities to address this question. Methods The Coronavirus SARS-CoV-2 and Diabetes Outcomes (CORONADO) initiative is a French, multicentric, cohort study of individuals with (exposed) and without diabetes (non-exposed) admitted to hospital with COVID-19, with a 1:1 matching on sex, age (±5 years), centre and admission date (10 March 2020 to 10 April 2020). Comorbidity burden was assessed by calculating the updated Charlson comorbidity index (uCCi). A predefined composite primary endpoint combining death and/or invasive mechanical ventilation (IMV), as well as these two components separately, was assessed within 7 and 28 days following hospital admission. We performed multivariable analyses to compare clinical outcomes between patients with and without diabetes. Results A total of 2210 pairs of participants (diabetes/no-diabetes) were matched on age (mean±SD 69.4±13.2/69.5±13.2 years) and sex (36.3% women). The uCCi was higher in individuals with diabetes. In unadjusted analysis, the primary composite endpoint occurred more frequently in the diabetes group by day 7 (29.0% vs 21.6% in the no-diabetes group; HR 1.43 [95% CI 1.19, 1.72], p<0.001). After multiple adjustments for age, BMI, uCCi, clinical (time between onset of COVID-19 symptoms and dyspnoea) and biological variables (eGFR, aspartate aminotransferase, white cell count, platelet count, C-reactive protein) on admission to hospital, diabetes remained associated with a higher risk of primary composite endpoint within 7 days (adjusted HR 1.42 [95% CI 1.17, 1.72], p<0.001) and 28 days (adjusted HR 1.30 [95% CI 1.09, 1.55], p=0.003), compared with individuals without diabetes. Using the same adjustment model, diabetes was associated with the risk of IMV, but not with risk of death, within 28 days of admission to hospital. Conclusions/interpretation Our results demonstrate that diabetes status was associated with a deleterious COVID-19 prognosis irrespective of age and comorbidity status. Trial registration ClinicalTrials.gov NCT04324736 Graphical abstract
When querying Knowledge Bases, users are faced with large sets of data, often without knowing their underlying structures. It follows that users may make mistakes when formulating their queries, therefore receiving an unhelpful response. In this paper, we address the plethoric answers problem, the situation where the user query produces significantly more results than the user was expecting. The common approach to solving this problem, i.e. the top-K approach, reduces the query’s result size by applying various criteria to select only some answers. This selection is performed without considering the causes producing plethoric answers, and can therefore miss an underlying issue within the query. We deal with this problem by proposing an approach that identifies the parts of the failing query, called Minimal Failure Inducing Subqueries (MFIS), that cause plethoric answers. As long as the query contains an MFIS, it will fail to reach a sufficiently low amount of answers. Thus, thanks to these MFIS, interactive and automatic approaches can be set up to help the user in reformulating their query. The dual notion of MFIS, called Maximal Succeeding Subqueries (XSS), is also useful. They provide queries with a maximal number of parts of the original query that return non-plethoric answers. Our goal is to compute MFIS and XSS efficiently, so that they may be used to solve the plethoric answers problem. We show that computing this information is an \(\texttt {NP}\)-hard problem. Thus, a baseline exhaustive search method cannot be used for most queries. We propose two algorithms that leverage properties of queries and data to compute MFIS and XSS efficiently for queries of reasonable size. We show experimentally that our two algorithms clearly outperform a baseline method on generated queries as well as real user-submitted queries.
Background Inhibiting SDH (succinate dehydrogenase), with the competitive inhibitor malonate, has shown promise in ameliorating ischemia/reperfusion injury. However, key for translation to the clinic is understanding the mechanism of malonate entry into cells to enable inhibition of SDH, its mitochondrial target, as malonate itself poorly permeates cellular membranes. The possibility of malonate selectively entering the at-risk heart tissue on reperfusion, however, remains unexplored. Methods C57BL/6J mice, C2C12 and H9c2 myoblasts, and HeLa cells were used to elucidate the mechanism of selective malonate uptake into the ischemic heart upon reperfusion. Cells were treated with malonate while varying pH or together with transport inhibitors. Mouse hearts were either perfused ex vivo (Langendorff) or subjected to in vivo left anterior descending coronary artery ligation as models of ischemia/reperfusion injury. Succinate and malonate levels were assessed by LC-MS/MS, in vivo by mass spectrometry imaging, and infarct size by TTC staining. Results Malonate was robustly protective against cardiac ischemia/reperfusion injury, but only if administered at reperfusion and not when infused before ischemia. The extent of malonate uptake into the heart was proportional to the duration of ischemia. Malonate entry into cardiomyocytes in vivo and in vitro was dramatically increased at the low pH (≈6.5) associated with ischemia. This increased uptake of malonate was blocked by selective inhibition of MCT1 (monocarboxylate transporter 1). Reperfusion of the ischemic heart region with malonate led to selective SDH inhibition in the at-risk region. Acid-formulation greatly enhances the cardioprotective potency of malonate. Conclusions Cardioprotection by malonate is dependent on its entry into cardiomyocytes. This is facilitated by the local decrease in pH that occurs during ischemia, leading to its selective uptake upon reperfusion into the at-risk tissue, via MCT1. Thus, malonate’s preferential uptake in reperfused tissue means it is an at-risk tissue-selective drug that protects against cardiac ischemia/reperfusion injury.
Minnows of the genus Phoxinus are common and an often highly abundant fish species in Palearctic freshwater habitats. Phoxinus species have a complex evolutionary history, phylogenetic relationships are not well understood, and there are number of unresolved taxonomic problems. There are currently 23 different mitochondrial genetic lineages identified in the genus Phoxinus, 13 of which are recognized as valid species. The taxonomic status of these lineages requires resolution, including the degree to which they can interbreed. Suitable nuclear molecular markers for studies of population divergence and interbreeding between morphotypes and mitochondrial lineages are lacking for Phoxinus species. Therefore, we developed a set of microsatellite markers using genomic information from Phoxinus lumaireul and tested their suitability for this and two related species, Phoxinus krkae and Phoxinus marsilii. Out of 16 microsatellite candidate loci isolated, 12 were found to be in Hardy‐Weinberg equilibrium when tested on two P. lumaireul senso lato populations. Seven loci amplified across the three species, enabling the study of intraspecific genetic diversity and population structure within P. marsilii and P. krkae. The markers were able to clearly resolve differences among the three tested species, including the recently described P. krkae, and therefore are suitable for the detection of introgression and hybridization among within populations consisting of mixtures of two or more of P. lumaireul s. l., P. marsilii and P. krkae. This article is protected by copyright. All rights reserved.
Circulating proteins associated with transforming growth factor–β (TGF-β) signaling are implicated in the development of diabetic kidney disease (DKD). It remains to be comprehensively examined which of these proteins are involved in the pathogenesis of DKD and its progression to end-stage kidney disease (ESKD) in humans. Using the SOMAscan proteomic platform, we measured concentrations of 25 TGF-β signaling family proteins in four different cohorts composed in total of 754 Caucasian or Pima Indian individuals with type 1 or type 2 diabetes. Of these 25 circulating proteins, we identified neuroblastoma suppressor of tumorigenicity 1 (NBL1, aliases DAN and DAND1), a small secreted protein known to inhibit members of the bone morphogenic protein family, to be most strongly and independently associated with progression to ESKD during 10-year follow-up in all cohorts. The extent of damage to podocytes and other glomerular structures measured morphometrically in 105 research kidney biopsies correlated strongly with circulating NBL1 concentrations. Also, in vitro exposure to NBL1 induced apoptosis in podocytes. In conclusion, circulating NBL1 may be involved in the disease process underlying progression to ESKD, and its concentration in circulation may identify subjects with diabetes at increased risk of progression to ESKD.
Background Cases of Toxoplasma reactivation or more severe primary infection have been reported in patients receiving immunosuppressive (IS) treatment for autoimmune diseases (AID). The purpose of this study was to describe features of toxoplasmosis occurring in patients with AID treated by IS therapy, excluded HIV-positive and transplant patients. Methods A multicenter descriptive study was conducted using data from the French National Reference Center for Toxoplasmosis (NRCT) that received DNA extracts or strains isolated from patients, associated with clinical data. Other cases were retrieved through a questionnaire sent to all French parasitology and internal medicine departments. Furthermore, a systematic literature review was conducted. Results 61 cases were collected: 25 retrieved by the NRCT and by a call for observations and 36 from a literature review. Half of the cases were attributed to reactivation (50.9%), and most of cases (49.2%) were cerebral toxoplasmosis. The most common associated AID were rheumatoid arthritis (28%) and most frequent treatments were antimetabolites (44.3%). Corticosteroids were involved in 60.7% of cases. Patients had a favorable outcome (50.8%) but nine did not survive. For 12 cases, a successful Toxoplasma strain characterization suggested the possible role of this parasitic factor in ocular cases. Conclusion Although this remains a rare condition, clinicians should be aware for the management of patients and for the choice of IS treatment.
Aims A unique Andean population lives in the highest city of the world (La Rinconada, 5,100 m, Peru) and frequently develops a maladaptive syndrome, termed chronic mountain sickness (CMS). Both extreme altitude and CMS are a challenge for the cardiovascular system. This study aims to evaluate cardiac remodelling and pulmonary circulation at rest and during exercise in healthy and CMS highlanders. Methods Highlanders living permanently at 3,800 m (n = 23) and 5,100 m (n = 55) with (n = 38) or without CMS (n = 17) were compared to 18 healthy lowlanders. Rest and exercise echocardiography were performed to describe cardiac remodelling, pulmonary artery pressure (PAP) and pulmonary vascular resistance (PVR). Total blood volume (BV) and haemoglobin mass were determined in all people. Results With the increase in altitude of residency, the right heart dilated with an impairment in right ventricle systolic function, while the left heart exhibited a progressive concentric remodelling with grade I diastolic dysfunction but without systolic dysfunction. Those modifications were greater in moderate-severe CMS patients. Mean PAP was higher both at rest and during exercise in healthy highlanders at 5,100 m. The moderate-severe CMS subjects had a higher PVR at rest and a larger increase in PAP during exercise. The right heart remodelling was correlated with PAP, total BV and SpO2. Conclusions Healthy dwellers at 5,100 m, exhibit both right heart dilatation and left ventricle concentric remodelling with diastolic dysfunction. Those modifications are even more pronounced in moderate-severe CMS subjects and could represent the limit of the heart's adaptability before progression to heart failure.
Background: Schools are ideal for promoting the mental health of school-age children, but the teachers' current knowledge is insufficient to play an influential role in mental health services at schools. Fortunately, however, teachers have a high sense of responsibility, interest, and talent to receive knowledge and the ability to participate in this field. This study aimed to examine whether a protocol focused on the role of teachers could identify, guide, and care for school-age children with behavioral and mental health problems. Method: The current research was a “before and after” pilot quasi-experimental study conducted in three elementary, secondary, and high schools. The main intervention consisted of a 5-h workshop based on a ready-to-use booklet for teachers conducted separately in each school. A total of 58 teachers and 872 school-age children were included using a judgmental sampling technique. Results: The pre-and post-workshop mean scores of teachers' knowledge about common mental disorders in school-age children were 6.21 ± 4.58 and 12.50 ± 7.27, respectively. According to the Strengths and Difficulties Questionnaire (SDQ), the teachers made 127 referrals, of whom 102 school-age children had problems. Consultants diagnosed 114 school children who reflected 90% of all teachers' recommendations needing psychological care and counseling. Finally, only 50 diagnosed school-age children were followed up and attended therapy sessions at counseling centers. The sensitivity and specificity of this brief intervention in detecting school-age children with psychological problems were respectively 80.3 and 98.0%. Conclusions: This study's results support teacher empowerment training's effectiveness in identifying and guiding school-age children needing mental health care. Psychological counseling programs in schools in various quantitative and qualitative dimensions, including responding to school-age children's needs and psychological problems, should be adequately evaluated, and appropriate measures should be taken to promote mental health services. Collaboration between health systems and the education department will increase the effectiveness of mental health programs' promotion and drug abuse prevention. These pilot data lead the way to designing scientifically sound follow-up studies that will concretely ascertain the benefit of this program.
An increasing number of numerical morphodynamic models predict the evolution of bed configuration over a wide spectrum of spatial and temporal scales due to the development of advanced numerical methods and increased computational power. The increasing use of numerical morphodynamic models is closely related to the growing availability of high‐resolution river data sets. Today, the main difficulty in using numerical morphodynamic models is that they are used by nonspecialists modellers or modellers that are not morphodynamics specialists, which can lead to errors. These errors include inadequate parameterization of processes for applications at larger spatial and temporal scales, confusion between physical and numerical phenomena when interpreting numerical results, and the assumption that there is a need for a huge volume of data for developing numerical morphodynamic models. The present work aims to achieve two objectives. To avoid these errors, the first objective is to outline the steps in the development of numerical morphodynamic models. The development of numerical morphodynamic models is now possible with public databases. The second objective is to show the effectiveness of BASEMENT to study the impact of existing and future structures on the river hydrodynamics and bedload transport using case study examples.
Objective Despite recent progress in caring for patients born with esophageal atresia (EA), undernutrition and stunting remain common. Our study objective was to assess nutritional status in the first year after birth with EA and to identify factors associated with growth failure. Study design We conducted a population-based study of all infants born in France with EA between 2010 and 2016. Through the national EA register, we collected prenatal to 1 year follow-up data. We used body mass index and length-for-age ratio Z scores to define patients who were undernourished and stunted, respectively. Factors with P < 0.20 in univariate analyses were retained in a logistic regression model. Results Among 1,154 patients born with EA, body mass index and length-for-age ratio Z scores at 1 year were available for about 61%. Among these, 15.2% were undernourished and 19% were stunted at the age of 1 year. There was no significant catch-up between ages 6 months and 1 year. Patients born preterm (41%), small for gestational age (17%), or with associated abnormalities (55%) were at higher risk of undernutrition and stunting at age 1 year ( P < 0.05). Neither EA type nor surgical treatment was associated with growth failure. Conclusion Undernutrition and stunting are common during the first year after birth in patients born with EA. These outcomes are significantly influenced by early factors, regardless of EA type or surgical management. Identifying high-risk patient groups with EA (i.e., those born preterm, small for gestational age, and/or with associated abnormalities) may guide early nutritional support strategies.
Amyotrophic lateral sclerosis (ALS) is a fatal motoneuron (MN) disease characterized by protein misfolding and aggregation leading to cellular degeneration. So far neither biomarker, nor effective treatment has been found. ATP signaling and P2X4 receptors (P2X4) are upregulated in various neurodegenerative diseases. Here we show that several ALS-related misfolded proteins including mutants of SOD1 or TDP-43 lead to a significant increase in surface P2X4 receptor density and function in vitro. In addition, we demonstrate in the spinal the cord of SOD1-G93A (SOD1) mice that misfolded SOD1-G93A proteins directly interact with endocytic adaptor protein-2 (AP2); thus, acting as negative competitors for the interaction between AP2 and P2X4, impairing constitutive P2X4 endocytosis. The higher P2X4 surface density was particularly observed in peripheral macrophages of SOD1 mice before the onset and during the progression of ALS symptoms positioning P2X4 as a potential early biomarker for ALS. P2X4 expression was also upregulated in spinal microglia of SOD1 mice during ALS and affect microglial inflammatory responses. Importantly, we report using double transgenic SOD1 mice expressing internalization-defective P2X4mCherryIN knock-in gene or invalidated for the P2X4 gene that P2X4 is instrumental for motor symptoms, ALS progression and survival. This study highlights the role of P2X4 in the pathophysiology of ALS and thus its potential for the development of biomarkers and treatments. We also decipher the molecular mechanism by which misfolded proteins related to ALS impact P2X4 trafficking at early pathological stage in cells expressing-P2X4.
Background/aim: Anaplastic ependymoma is a rare cancer of the central nervous system. The treatment includes optimal resection with focal radiotherapy. Some case reports or retrospective studies have suggested efficacy of regimens containing platinum or bevacizumab. We describe the feasibility and clinical benefit of the cisplatin-bevacizumab-cyclophosphamide treatment of anaplastic ependymoma. Patients and methods: Patients were identified through the Adolescent and Young Adults (AYAS) brain tumor national Web conference. We estimated the median progression-free (PFS) and overall survival (OS). Results: There were eight patients with anaplastic ependymoma, with a median age of 36 years. The median OS was 19.9 months and median PFS was 12.3 months. Three patients obtained partial response, four stable disease, and one patient had disease progression during induction. Six patients received maintenance with a median duration of 224 days. Conclusion: This study confirms the tolerance of bevacizumab-cyclophosphamide-cisplatin treatment of anaplastic ependymoma. The clinical benefit seems even superior to that described in the literature.
Contexte Plusieurs études et rapports ont objectivé un état de mal-être chez les étudiants en santé. Cette situation justifie le besoin de mettre en place des interventions de promotion de la santé et du bien-être pendant la formation initiale de ces étudiants. Méthodes A Poitiers, une intervention baptisée « Happy'Doc » a été développée depuis l'année universitaire 2018-2019. « Happy'doc » est un séminaire de trois jours organisé sous forme de conférences théoriques et d'ateliers pratiques qui s'adressent aux étudiants en début de cursus de santé. Le séminaire portait sur six thématiques en lien direct avec un mode de vie sain : i) activités physiques et sportives, ii) nutrition, iii) gestion du stress, iv) santé environnementale, v) culture, vi) addiction. Un questionnaire de satisfaction a été diffusé. Résultats Au total, 842 étudiants en santé (médecine, pharmacie et orthophonie) ont participé aux trois premières éditions du séminaire « Happy'Doc ». Leurs retours étaient très positifs, notamment concernant l'organisation et concernant les ateliers collectifs. Par ailleurs, l'analyse du questionnaire de satisfaction a permis d'objectiver le renforcement des liens entre les étudiants de la même discipline de santé, ainsi que les liens interdisciplinaires. Les remarques des étudiants ont été prises en compte pour l'adaptation de l'intervention d'année en année. Discussion/Conclusion « Happy'Doc » est une intervention originale de promotion du bien-être adressée aux étudiants en santé. Le bien-être étant un facteur-clé dans la réussite académique des étudiants, il est important de multiplier ce type d'interventions tout au long du cursus et de le généraliser à l'ensemble des étudiants de l'université. Déclaration de liens d'intérêts Les auteurs déclarent ne pas avoir de liens d'intérêts.
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4,148 members
Guillaume Daver
  • Département Géosciences
Clarisse Vandebrouck
  • UFR of fundamental sciences
Yann Batonneau
  • Institut de Chimie des Milieux et Matériaux de Poitiers (IC2MP) (UMR 7285)
Mouloud Benammi
  • PALEVOPRIM - Paleontology Evolution Paleoecosystems Paleoprimatology (UMR CNRS 7262)
86000, Poitiers, Poitou-Charentes, France