Oskar Bordeaux
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    Nature

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    Macrophages specialize in phagocytosis, a cellular process that eliminates extracellular matter, including microorganisms, through internalization and degradation. Despite the critical role of phagocytosis during bacterial infection, the fate of phagocytosed microbial cargo and its impact on the host cell are poorly understood. In this study, we show that ingested bacteria constitute an alternative nutrient source that skews immunometabolic host responses. By tracing stable isotope-labelled bacteria, we found that phagolysosomal degradation of bacteria provides carbon atoms and amino acids that are recycled into various metabolic pathways, including glutathione and itaconate biosynthesis, and satisfies the bioenergetic needs of macrophages. Metabolic recycling of microbially derived nutrients is regulated by the nutrient-sensing mechanistic target of rapamycin complex C1 and is intricately tied to microbial viability. Dead bacteria, as opposed to live bacteria, are enriched in cyclic adenosine monophosphate, sustain the cellular adenosine monophosphate pool and subsequently activate adenosine monophosphate protein kinase to inhibit the mechanistic target of rapamycin complex C1. Consequently, killed bacteria strongly fuel metabolic recycling and support macrophage survival but elicit decreased reactive oxygen species production and reduced interleukin-1β secretion compared to viable bacteria. These results provide a new insight into the fate of engulfed microorganisms and highlight a microbial viability-associated metabolite that triggers host metabolic and immune responses. Our findings hold promise for shaping immunometabolic intervention for various immune-related pathologies

    PLoS One

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    Background The announcement of a diagnosis can be a source of anxiety for patients. Managing this anxiety is a major challenge, in terms of quality of life but also for the use of anxiolytic and analgesic therapies. The use of 3D modeling technology in partial nephrectomy surgery has proved its worth as a surgical aid but it could also help patients to manage their own care, by reducing their anxiety and increasing their understanding of the disease and its treatment. We aim to test this hypothesis with a prospective multicenter trial. Methods R3DP-A (Rein 3D – Anxiety) is an unblinded, multicenter, randomized, prospective, superiority-controlled trial. Participants are patients with kidney tumors treated by robot-assisted partial laparoscopic nephrectomy. The 234 patients (78x3 groups) from 6 French centers will undergo a pre-operative consultation dedicated to a personalized explanation of the surgical management and its risks. They will be randomized into three (1:1:1) groups corresponding to three types of support for consultation: use of a virtual 3D model of the kidney and its tumor; a printed 3D model; or the standard information sheet from the French Association of Urology (control group). Several self-questionnaires will be sent by the UroConnect® application and completed at different times during the study. The primary endpoint will be pre-operative anxiety (STAI-state questionnaire completed the day before surgery D-1). Secondary endpoints will be changes in anxiety levels between the pre-operative and post-operative consultations (between inclusion and D15 post-op), changes in health literacy and quality of life (HLSEU-Q16 and EQ-5D-5L questionnaires at inclusion and D15), feelings of understanding of the disease and its treatment at pre-operative period (Wake questionnaire at D-1), and consultation times. Discussion We aim to highlight a benefit of using a personalized 3D model on the anxiety level of patients undergoing partial nephrectomy surgery, as well as on their level of understanding of their pathology and its surgical treatment. The use of these models could be incorporated into current practice to improve patient experience throughout care. © 2025 Pitout et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Enhanced surgical kidney cancer care through digital and 3D technologie

    Identification and evolution of rickets and scurvy therapeutics between the 17th and 19th centuries CE: archaeo- and palaeopharmacological approach

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    In France, during the 18th-19th centuries, the period of industrial transition saw major socio-economic changes that had an impact on population health, and in particular on deficiency diseases such as rickets and scurvy. As part of health archaeology , this study combines two complementary approaches: archaeopharmacology - identification of therapeutics through artefacts and textual sources (e.g. ancient medical theses and treatises, pharmacopoeia, archives) and palaeopharmacology - identification of therapeutics through archaeometric analysis of ancient human remains (e.g. bones, teeth, dental calculus). For rickets and scurvy, medico-historical literature has traced traditional treatments based on plant (e.g. hemlock, opium, cinchona), animal (cod liver oil), or metals such as mercury. Despite its toxicity, mercury was widely used in medicine since the 17th century in syrups, ointments, and fumigations.The palaeopathological study of individual SP5, a 3- to 4-year-old child from the Rue Thubeuf cemetery in Rouen (late 18th-19th centuries), revealed multiple signs of bone deficiencies, likely attributable to rickets and scurvy. His osteoarchaeological remains were analysed for mercury content. The SP5 deciduous second molar was sampled to detect signs of vitamin D deficiency responsible for rickets in the dentine, using micro-computed tomography to obtain deficiencies information occurring during tooth development as dental tissues are not remodelled during life. In contrast, a thoracic vertebra was selected to gather information about the last months of life. Mercury was detected in these samples using a three-stage protocol to minimise the invasive nature of the study: 1- detection by ED-XRF (Energy Dispersive X-ray Fluorescence), 2- quantification by CV-AAS (Cold Vapour-Atomic Absorption Spectrometry), 3- localisation in the mineral structure by LIBS (Laser Induced Breakdown Spectroscopy).A minor episode of deficiency between birth and six months of age was detected by μCT, but was not related to observed bone deformities. However, the ED-XRF spectrum of the bone sample revealed a mercury peak, which was not observable in the dental sample. CV-AAS analysis revealed a high concentration of mercury in the vertebra (9.373 mg/kg ± 10%). The high mercury concentration in the vertebra suggests severe ante-mortem intoxication, supporting thehypothesis of mercury treatment for deficiencies, as other contamination sources (e.g., Rouen’s socio-cultural context, soil metallogeny, environmental factors, occupational exposure) were ruled out. In conclusion, SP5 may represent the first documented case of mercury treatment for vitamin deficiency, highlighting the value of paleopharmacology in linking archaeometric data with historical medical sources to better understand past therapeutic practices

    Nouveaux regards sur le vivant

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    Sequencing, de novo assembly of Ludwigia plastomes, and comparative analysis within the Onagraceae family

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    The Onagraceae family, which belongs to the order Myrtales, consists of approximately 657 species and 17 genera. This family includes the genus Ludwigia L., which is comprised of 82 species. In this study, we focused on the two aquatic invasive species Ludwigia grandiflora subsp. hexapetala (Lgh) and Ludwigia peploides subsp. montevidensis (Lpm) largely distributed in aquatic environments in North America and in Europe. Both species have been found to degrade major watersheds leading ecological and economical damages. Genomic resources for Onagraceae are limited, with only Ludwigia octovalvis (Lo) plastid genome available for the genus Ludwigia L. at the time of our study. This scarcity constrains phylogenetic, population genetics, and genomic studies. To brush up genomic ressources, new complete plastid genomes of Ludwigia grandiflora subps. hexapetala (Lgh) and Ludwigia peploides subsp. montevidensis (Lpm) were generated using a combination of MiSeq (Illumina) and GridION (Oxford Nanopore) sequencing technologies. These plastomes were then compared to the published Ludwigia octovalvis (Lo) plastid genome, which was re-annotated by the authors. We initially sequenced and assembled the chloroplast (cp) genomes of Lpm and Lgh using a hybrid strategy combining short and long reads sequences. We observed the existence of two Lgh haplotypes and two potential Lpm haplotypes. Lgh, Lpm, and Lo plastomes were similar in terms of genome size (around 159 Kb), gene number, structure, and inverted repeat (IR) boundaries, comparable to other species in the Myrtales order. A total of 45 to 65 SSRs (simple sequence repeats), were detected, depending on the species, with the majority consisting solely of A and T, which is common among angiosperms. Four chloroplast genes (matK,accD, ycf2 and ccsA) were found under positive selection pressure, which is commonly associated with plant development, and especially in aquatic plants such as Lgh, and Lpm. Our hybrid sequencing approach revealed the presence of two Lgh plastome haplotypes which will help to advance phylogenetic and evolutionary studies, not only specifically for Ludwigia, but also the Onagraceae family and Myrtales order. To enhance the robustness of our findings, a larger dataset of chloroplast genomes would be beneficial

    A new capulavirus infecting sugar beet (Beta vulgaris L.) in France

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    A novel capulavirus was identified by high-throughput sequencing in four sugar beet (Beta vulgaris L.) plants collected in April 2023 in Normandy (France). The complete genome of 2744 nucleotides (nt) was sequenced and found to have an organization similar to that of known capulaviruses, with which it showed close phylogenetic relationships. In addition, data mining of a publicly available Thalictrum thalictroides whole-genome shotgun sequence assembly allowed the identification of a contig (JABWDY010003008.1) representing a longer-than-unit length, likely episomal, genome with 99.4% nt sequence identity to the genome of the French beet isolate. The genome of the novel virus shares only 60.7–66.9% nt sequence identity with known capulaviruses, which is well below the species demarcation threshold of 78%, suggesting that a new species should be created to accommodate it. The common name "beet capulavirus 1" (BCV1) is proposed for this novel virus. Given that BCV1 was identified in plants that were coinfected with beet yellows virus, no conclusions can be drawn at this stage about its potential pathogenicity

    A new conservative and robust Bayesian approach for the event date model in chronology building

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    Dating techniques in archaeology have undergone considerable development in recent decades. Today, the major challenge for archaeologists remains the reliability and precision of the date attributed to an artefact or an archaeological event. To this end, it is essential for archaeologists to cross-reference information from different sources (absolute dating, relative dating, typo-chronology, historical texts, etc.) The development of statistical models that are as close as possible to archaeological reasoning is necessary for efficient data processing. Research published over the past thirty years has shown that statistical models based on the Bayesian statistical approach are ideally suited to the construction of chronologies. Indeed, Bayesian modeling makes it possible to combine the chronometric measurements produced in dating laboratories and the expertise of archaeologists. Moreover, Bayesian statistics are also well suited to small samples (i.e., few dating data). In this article, we are interested in the event date model proposed by Lanos and Philippe in 2017. It is a hierarchical Bayesian model that allows combining chronometric dates assumed to be contemporaneous to estimate the date of a target event of historical interest. Irreducible errors between the chronometric dates and the event of interest are modeled with individual random effects, which makes it a model robust to outliers. However, the introduction of individual random effects can lead to imprecision of the posterior density of the event date. The aim of this article is to correct this imprecision by making the event date model conservative.In this article, we first calculate the theoretical posterior densities of the parameters of the event date model proposed by Lanos and Philippe for two cases, namely the processing of chronometric measurements and the processing of typo-chronological observations. Secondly, we propose an improvement to this model by assuming randomness in the precision parameter, which we model here by a prior inverse-gamma distribution whose parameters are defined under the constraint of conservation of the event date distribution when it contains a single chronometric date. We illustrate this improvement by applying it to synthetic examples (usual distributions and calibrated distributions), then to data from various archaeological structures that have already been published

    Intern Emerg Med

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    The impact of total time from emergency department (ED) admission to geriatric ward admission in older patients remains unknown. The objective of the study was to assess the association between time to geriatric ward admission on 6-month mortality and functional decline in older adults. A prospective, single-center cohort study was conducted including patients 75 years or older admitted to an acute-care geriatric unit following an ED visit in 2023 with a 6-month follow-up. Functional decline was defined as a decrease of at least 1 point in the Activities of Daily Living (ADL) scale between admission and 6 months. The primary end point was a composite of 6-month mortality and functional decline. Association between quartiles of time to geriatric ward admission and the primary end point was analyzed using multivariable logistic regression. Among the 360 included patients (median age 86, median time to geriatric ward admission 32.2 h), 198 (55%) experienced the composite outcome (31% death and 24% functional decline): 42%, 47%, 60%, and 71% in the first to last quartile, respectively. Compared to the first quartile, there was an independent association between time to geriatric ward admission and the primary outcome with an adjusted odds ratios of 1.4 (95% CI 0.8–2.7), 2.3 (95% CI 1.2–4.3), and 3.4 (95% CI 1.8–6.6) for the second, third, and fourth quartiles, respectively. Prolonged time to geriatric ward admission following ED consultation is associated with a higher risk of 6-month mortality and functional decline in older adults. Trial registration 2023-A02753-42 (CPP Sud-Est V approval). © The Author(s), under exclusive licence to Società Italiana di Medicina Interna (SIMI) 2025

    Chemical exchange saturation transfer magnetic resonance imaging for metabolic mapping of ripening tomato fruit: Quite a challenge!

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    Chemical Exchange Saturation Transfer Magnetic Resonance Imaging (CEST-MRI) is an established tool in animal or human MRI to indirectly visualize metabolites in vivo. We used CEST-MRI to map the major metabolites in tomato fruit at tissue level throughout ripening. Phantom experiments showed a CEST effect in the 1 and 3 ppm chemical shifts for major soluble sugars and free amino acids, respectively, and a tendency for the CEST signal to decrease from pH 4.7 to 3.7. Fruit images for hydroxyl or amine moieties were well-contrasted for all ripening stages, showing gradients within and between tissues. Mean hydroxyl-CEST signals correlated with the ex vivo concentrations of soluble sugars of dissected tissues, although this was not the case for amino acids. This approach holds much promise for monitoring composition changes in vivo within a plant organ tissue.Développement d'une infrastructure française distribuée pour la métabolomique dédiée à l'innovatio

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    Oskar Bordeaux is based in France
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