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Introduction: Despite improved management of traumatic brain injury (TBI), it still leads to lifelong sequelae and disability, particularly in children. Chronic neuroinflammation (the so-called tertiary phase), in particular, microglia/macrophage and astrocyte reactivity, is among the main mechanisms suspected of playing a role in the generation of lesions associated with TBI. The role of acute neuroinflammation is now well understood, but its persistent effect and impact on the brain, particularly during development, are not. Here, we investigated the long-term effects of pediatric TBI on the brain in a mouse model., Methods: Pediatric TBI was induced in mice on postnatal day (P) 7 by weight-drop trauma. The time course of neuroinflammation and myelination was examined in the TBI mice. They were also assessed by magnetic resonance, functional ultrasound, and behavioral tests at P45., Results: TBI induced robust neuroinflammation, characterized by acute microglia/macrophage and astrocyte reactivity. The long-term consequences of pediatric TBI studied on P45 involved localized scarring astrogliosis, persistent microgliosis associated with a specific transcriptomic signature, and a long-lasting myelination defect consisting of the loss of myelinated axons, a decreased level of myelin binding protein, and severe thinning of the corpus callosum. These results were confirmed by reduced fractional anisotropy, measured by diffusion tensor imaging, and altered inter- and intra-hemispheric connectivity, measured by functional ultrasound imaging. In addition, adolescent mice with pediatric TBI showed persistent social interaction deficits and signs of anxiety and depressive behaviors., Conclusions: We show that pediatric TBI induces tertiary neuroinflammatory processes associated with white matter lesions and altered behavior. These results support our model as a model for preclinical studies for tertiary lesions following TBI., (Copyright © 2024. Published by Elsevier Inc.)

Background: Vaccine-induced immune thrombotic thrombocytopenia (VITT) is a complication of adenoviral-based vaccine against SARS-CoV-2 due to prothrombotic immunoglobulin (Ig) G antibodies to platelet factor 4 (PF4) and may be difficult to distinguish from heparin-induced thrombocytopenia (HIT) in patients treated with heparin., Objectives: We assessed the usefulness of competitive anti-PF4 enzyme immunoassays (EIAs) in this context., Methods: The ability of F(ab')2 fragments of 1E12, 1C12, and 2E1, 3 monoclonal anti-PF4 antibodies, to inhibit the binding of human VITT or HIT antibodies to PF4 was evaluated using EIAs. Alanine-scanning mutagenesis was performed to define the amino acids involved in the interactions between the monoclonal antibodies and PF4., Results: A strong inhibition of VITT IgG binding to PF4 was measured with 1E12 (median inhibition, 93%; n = 8), whereas it had no effect on the binding of HIT antibodies (median, 6%; n = 8). In contrast, 1C12 and 2E1 inhibited VITT (median, 74% and 76%, respectively) and HIT antibodies (median, 68% and 53%, respectively) binding to PF4. When a competitive anti-PF4 EIA was performed with 1E12 for 19 additional VITT samples, it strongly inhibited IgG binding to PF4, except for 1 patient, who had actually developed HIT according to the clinical history. Epitope mapping showed that 1E12 interacts with 5 key amino acids on PF4, of which 4 are also required for the binding of human VITT antibodies, thus explaining the competitive inhibition., Conclusion: A simple competitive anti-PF4 EIA with 1E12 could help confirm VITT diagnosis and distinguish it from HIT in patients when both diagnoses are possible., Competing Interests: Declaration of competing interests C.V. reports honorarium from Viatris. J.R. reports research grant from Stago. H.G. reports transport fees from Stago. F.M. reports speaker fees from Fresenius, Technoclone, and Werfen, all outside the submitted work. Y.G. reports research grant and symposium fees from Stago. C.P. reports research grant from Stago. All other authors of this paper have no conflicts of interest., (Copyright © 2024 International Society on Thrombosis and Haemostasis. Published by Elsevier Inc. All rights reserved.)

X-linked hypophosphatemia (XLH) is a rare, multi-systemic, invalidating disease requiring a multi-disciplinary approach. No specific action in XLH, neither for the patients' specific needs nor for the methodology for the evaluation of these were found. Thus, to identify the needs of XLH patients and their caregivers, we organised focus groups in our reference centre with a view to build educational sessions. Focus groups including either XLH children, XLH adults, or caregivers ran in parallel. Each group was led by a person trained in therapeutic education (nurse, paediatric nephrologist) with another healthcare provider specialised in XLH (rheumatologist, nephrologist). One additional person with knowledge of XLH (clinical research associate, paediatric resident) took minutes. The duration of each session was 1.5h; XLH patients/caregivers were asked to answer age-adapted "open questions" on their daily life and quality of life. At the end, a global restitution was made. The needs identified were later grouped and analysed, which allowed us to build the educational sessions. The XLH children group included 5 children, the XLH adults group included 10 adults, and the caregivers group included 6 parents or partners. Major needs were identified: knowledge of XLH, treatment, dental care and adapted physical activity, with additional questions on socio-professional adaptations and financial support in adults. Partner patients were also identified to co-build the support programme. The study allowed us to identify the needs of XLH patients and their caregivers using the focus group method and then, using these needs, to build educational sessions and a therapeutic education programme for XLH patients., Competing Interests: Declaration of competing interest The authors have no competing interests to declare that are relevant to the content of this article., (Copyright © 2024. Published by Elsevier Masson SAS.)

Introduction: Primary hyperoxaluria (PH) is a rare genetic disorder of hepatic glyoxylate metabolism. Nedosiran is an RNA interference (RNAi) therapeutic that the US Food and Drug Administration has approved for treatment of PH1. PHYOX3 is a trial evaluating monthly nedosiran in patients with PH., Methods: In this PHYOX3 interim analysis, participants with PH1 who continued from a single-dose nedosiran trial (PHYOX1), with no previous kidney or liver transplantation, dialysis, or evidence of systemic oxalosis were eligible. The safety and efficacy of once-monthly nedosiran was assessed over 30 months., Results: Thirteen participants completed PHYOX1 and continued into PHYOX3. At baseline, the mean (SD) and median (range) age was 24.2 (6.6) years and 23.0 (14-39) years, respectively; 53.8% were female and 61.5% were White. Mean estimated glomerular filtration rate (eGFR) remained stable (62-84.2 mL/min per 1.73 m 2 ) to month 30. Mean 24-hour urinary oxalate (Uox) excretion showed a sustained reduction from baseline of ≥60% at every visit (months 2-30). From month 2, at least 10 of 13 (76.9%) participants achieved normal (<0.46 mmol/24h; upper limit of assay-normal [ULN]) or near-normal (≥0.46 to <0.60 mmol/24h; ≥ULN to <1.3 × ULN) 24-hour Uox excretion. All participants experienced ≥1 adverse event (AE), mostly mild or moderate in severity (primarily, injection site events). Three serious, not treatment-related AEs were reported; there were no deaths or study discontinuations due to AEs., Conclusion: Nedosiran was well-tolerated in patients with PH1, and treatment resulted in a sustained, substantial reduction in Uox excretion for at least 30 months in this long-term study. No safety signals have been identified to date. The PHYOX3 study is ongoing., (© 2024 International Society of Nephrology. Published by Elsevier Inc.)

Introduction: Patients with short bowel syndrome (SBS) may exhibit enteric hyperoxaluria (EH), and the prevalence of oxalate nephropathy in SBS is likely underestimated. Plasma oxalate (POx) is a surrogate of systemic oxalate deposition and, consequently, may increase the risk of developing chronic kidney disease (CKD). The main objective of this study was to explore the distribution of POx levels in patients with SBS., Methods: Patients followed for SBS were recruited prospectively in the OXAGO study (NCT04119765) to assess POx during their annual renal follow-up including iohexol clearance. The inclusion criteria were age ≥18 years, and SBS type 2 and type 3 for more than 6 months., Results: A total of 47 patients were included but only 45 patients has a measured POx (55% males, 80% SBS type 2, 66% parenteral nutrition, 61% kidney stone history). POx levels were 6.8 ± 4.4 μmol/l, 29% of patients had POx ≥5 μmol/l. In the whole cohort, mean urinary oxalate (UOx) was 648±415 and 54% were >500 μmol/24h. In the group of patients with high POx levels (HPO), 24-hour urine oxalate was significantly higher than in the group with normal POx levels (NPO) (919 ± 566 vs. 526 ± 257 μmol/l; P  = 0.003). Glomerular filtration rate (GFR) was 66 ± 22 ml/min per 1.73 m 2 , and 91% had CKD. GFR was significantly lower in the HPO than in the NPO group (49 ± 23 vs. 73 ± 18 ml/min per 1.73 m 2 ; P  = 0.0005., Conclusion: Patients with SBS can display increased POx levels even with GFR >30 ml/min per 1.73 m 2 . POx may be an interesting biomarker to assess the severity of EH., (© 2024 International Society of Nephrology. Published by Elsevier Inc.)

Parathyroid hormone (PTH) is a hypercalcemic hormone acting on kidneys, bone and intestine. PTH promotes calcium release from the bone, renal calcium reabsorption and phosphate excretion, and conversion of 25-hydroxyvitamin D to 1,25-dihydroxyvitamin D-3. Hyperparathyroidism consists in PTH elevation, which may be adapted (secondary hyperparathyroidism) or non-adapted to calcemia levels (primary hyperparathyroidism, familial hypercalcemia/hypocalciuria, tertiary hyperparathyroidism). Primary hyperparathyroidism (PHP) features hypercalcemia and elevated or inappropriate PTH elevation. PHP may be revealed by biological abnormalities such as hypercalcemia and can be accompanied by renal complications (hypercalciuria, nephrolithiasis, nephrocalcinosis) and/or osteoporosis. However, it can also be normocalcemic and calcium loading will be necessary to diagnosis it. The differential diagnosis of PHP is familial hypocalciuric hypercalcemia (FHH), a dominant autosomal disease implicating a calcium sensing receptor-inactivating mutation. It impairs parathyroid cell sensitivity to calcemia elevation and thus induces excessive PTH stimulation, leading to hypercalcemia. Secondary HP (SHP) consists in PTH elevation secondary to a stimulus that needs to be corrected. 25 OHvitD deficiency, kidney failure, renal hypercalciuria, malabsorption and some drugs can induce SHP. Tertiary HP (THP) consists in autonomous PTH secretion by the parathyroid glands after prolonged stimulation under SHP, of whatever cause. This parathyroid autonomy results from the polyclonal hyperplasia observed in SHP progressing toward monoclonal nodular proliferation, leading to nodular hyperplasia or parathyroid adenoma (or, exceptionally, carcinoma), with reduced expression of CaSR and vitamin D receptor. In patients under dialysis, the frontier between SHP and THP is a matter of debate. This review will focus on the pathophysiology of calcium, diagnosis, and management of hyperparathyroidism., (Copyright © 2022 Elsevier Masson SAS. All rights reserved.)

Background and Aims: Patients with inflammatory bowel diseases (IBD) are exposed to drug-related nephrotoxicity and kidney-related extra-intestinal manifestations (EIMs). Patients should be monitored but guidance is lacking in current international recommendations. The objective of the Kidney Function Monitoring in Inflammatory Bowel Disease (MONITORED) initiative was to achieve an expert consensus about monitoring kidney function in IBD., Methods: A literature review was first conducted. Then, an expert consensus meeting, involving 28 attendees representing French-speaking gastroenterologists and nephrologists, was held as part of an academic initiative on May 28, 2021. An anonymous Delphi process was used to discuss and vote on statements. Agreement was defined as at least 75% of participants voting for any one statement., Results: Experts reached consensus on 11 criteria for referral to the nephrologist. Concerning kidney function monitoring, participants unanimously validated the use of serum creatinine with estimation of the glomerular filtration rate via the MDRD or CKD-EPI equations. A blood ionogram and a urine sample with measurement of a protein-to-creatinine ratio were also broadly agreed validated. Experts recommended performing this monitoring at IBD diagnosis, prior introducing a new treatment, and annually for EIMs screening and evaluation of treatment tolerance. An evaluation 3 months after starting mesalamine and then every 6 months was felt necessary, while for biologics an annually monitoring was deemed sufficient., Conclusion: The MONITORED consensus proposed guidelines on how to monitor kidney function in IBD. These recommendations should be considered in clinical practice to preserve kidney function and ensure the best approach to our patients., Competing Interests: Conflict of interest L Guillo declares consulting fees for Abbvie. A Amiot declares counseling, boards, lecture, transports or fees from Abbvie, Hospira, Takeda, Gilead, Biocodex, Janssen, Ferring and MSD. B Caron has received lecture and/or consulting fees from Abbvie, Amgen, Celltrion, Janssen, Takeda. G Boschetti has served as a speaker and advisory board member for Abbvie, Janssen, Ferring, Norgine, Tillotts, Pfizer, Celltrion, Takeda, Amgen, Sandoz. G Bouguen has received lecture fees from Abbvie, Ferring, MSD, Takeda, Otsuka, Amgen, Biogen, Celtrion, Janssen, Tillots and Pfizer and consultant fees from Takeda, Janssen, Mylan, Vifor Pharma and Gilead. JM Gornet has received personal fees from Amgen, Janssen Cilag, Sanofi, Takeda, Roche and Tillots Pharma. J Bonnet has received consulting fees for Amgen. L Vuitton has received lecture fees from Abbvie, MSD, Takeda, Ferring, Janssen and Pfizer, and research grants from MSD, Takeda and Pfizer. M Nachury received board membership, consultancy, or lecture fees from Abbvie, Adacyte, Amgen, Arena, CTMA, Celltrion, Ferring, Fresenius-Kabi, Janssen, Mayoli-Spindler, MSD, Pfizer, Takeda. M Uzzan has served as a speaker for Janssen and Abbvie. M Serrero declares lecture and consulting fees for Abbvie, Celltrion, Ferring, Janssen, MSD, Takeda and Tillotts. L Peyrin-Biroulet has served as a speaker, consultant and advisory board member for Merck, Abbvie, Janssen, Genentech, Mitsubishi, Ferring, Norgine, Tillotts, Vifor, Hospira/Pfizer, Celltrion, Takeda, Biogaran, Boerhinger-Ingelheim, Lilly, HAC- Pharma, Index Pharmaceuticals, Amgen, Sandoz, For- ward Pharma GmbH, Celgene, Biogen, Lycera, Samsung Bioepis, Theravance. The remaining authors declare no conflict of interest., (Copyright © 2021 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Adipose tissue is the energy storage organ providing energy to other tissues, including mammary gland, that supports the achievement of successive lactation cycles. Our objective was to investigate the ability of goats to restore body fat reserves by comparing lipogenic enzyme activities and by transcriptomic RNA-Seq data at two different physiological stages, mid- and post-lactation. Key lipogenic enzyme activities were higher in goat omental adipose tissue during mid-lactation (74 days in milk) than during the post-lactation period (300 days postpartum). RNA-Sequencing analysis revealed 19,271 expressed genes in the omental adipose tissue. The comparison between adipose transcriptome analysis from mid- and post-lactation goats highlighted 252 differentially expressed genes (p adj  < 0.05) between these two physiological stages. The differential expression of 11 genes was confirmed by RT-qPCR. Functional genomic analysis revealed that 31% were involved in metabolic processes among which 38% in lipid metabolism. Most of the genes involved in lipid synthesis and those in lipid transport and storage were upregulated in adipose tissue of mid- compared to post-lactation goats. In addition, adipose tissue plasticity was emphasized by genes involved in cellular signaling and tissue integrity. Network analyses also highlighted three key regulators of lipid metabolism (LEP, APOE and HNF4A) and a key target gene (VCAM1). The greatest lipogenic enzyme activities with the upregulation of genes involved in lipid metabolism highlighted a higher recovery of lipid reserves after the lactation peak than 4 months post-lactation. This study contributes to a better understanding of the molecular mechanisms controlling the body lipid reserves management during the successive lactations., (Copyright © 2021. Published by Elsevier Inc.)

Introduction: Glomerular filtration rate (GFR) is measured from the late plasma disappearance curve of an exogenous tracer, after correction for the early decay-corresponding to the distribution of the tracer-using various equations. These equations display the highest discrepancies in the GFR range above 90 ml/min per 1.73 m 2 , and their respective performances against a reference, urinary GFR measurement are unclear., Methods: In patients with mGFR >90 ml/min per 1.73 m 2 from 6 different cohorts, we compared GFR obtained from the plasma clearance of iohexol or 51 Cr-ethylenediamine tetraacetic acid (EDTA), after correction using Chantler (C), Bröchner-Mortensen (BM), Fleming (F), Jodal-Bröchner-Mortensen (JBM), and Ng (N) equations, with urinary clearance of the same tracers or inulin., Results: In 438 participants (median age 41 [39-42] years, 43% women), the median urinary clearance was 100.8 (94.7-112.6) ml/min per 1.73 m 2 . Plasma clearances using the correction equations were 105.7 (96.8-119.2), 102.4 (95.2-112.9), 100.7 (93.6-111.1), 102.6 (95.2-113.4), and 106.0 (98.2-117.6) ml/min per 1.73 m 2 for C, BM, F, JBM, and N, respectively. Concordance correlation coefficients between plasma and urinary clearances were poor for all equations. Compared with urinary clearances, BM, F, and JBM displayed the best accuracy within 10% (73%, 72%, and 71%, respectively, vs. 63% and 66% for C and N), whereas BM and JBM had the lowest median biases. Accuracy of all equations was especially low in the hyperfiltration range (urinary clearance >130 ml/min per 1.73 m 2 )., Conclusion: The BM and JBM equations displayed the best overall performances to correct for the early disappearance curve. Results of these equations should be interpreted with caution, especially in the highest GFR range., (© 2021 International Society of Nephrology. Published by Elsevier Inc.)

Rare diseases of phosphate/calcium metabolism correspond to a wide and heterogeneous spectrum of diseases. Recent knowledge in physiology and genetics has made it possible to better characterize them and to propose attractive therapeutic approaches based on the underlying pathophysiology. These diseases are often at the interface between nephrology and endocrinology. In this spirit of a multidisciplinary care, each specialty can bring its own critical point of view and its own specificities to improve patient care. The objective of this manuscript is to "read" with a nephrologist's point of view the main frameworks of diseases of phosphate/calcium metabolism, to illustrate the three crucial messages of nephro-protection sent to endocrinologists. First, calciuria must be interpreted both in absolute value (concentration hypercalciuria) and in ratio (flow hypercalciuria). Second, renal monitoring of therapies inducing hypercalciuria on kidneys with normal renal function (e.g. active vitamin D analogs or teriparatide) should be systematic. Last, hyperphosphatemia, often latent in hypoparathyroidism and pseudo-hypoparathyroidism, should be detected and at least benefit from dietary measures, in the context of Western diets rich in phosphate hidden in food additives., (Copyright © 2020. Published by Elsevier Masson SAS.)

Microplastics are ubiquitous in aquatic ecosystems, but little information is currently available on the dangers and risks to living organisms. In order to assess the ecotoxicity of environmental microplastics (MPs), samples were collected from the beaches of two islands in the Guadeloupe archipelago, Petit-Bourg (PB) located on the main island of Guadeloupe and Marie-Galante (MG) on the second island of the archipelago. These samples have a similar polymer composition with mainly polyethylene (PE) and polypropylene (PP). However, these two samples are very dissimilar with regard to their contamination profile and their toxicity. MPs from MG contain more lead, cadmium and organochlorine compounds while those from PB have higher levels of copper, zinc and hydrocarbons. The leachates of these two samples of MPs induced sublethal effects on the growth of sea urchins and on the pulsation frequency of jellyfish ephyrae but not on the development of zebrafish embryos. The toxic effects are much more marked for samples from the PB site than those from the MG site. This work demonstrates that MPs can contain high levels of potentially bioavailable toxic substances that may represent a significant ecotoxicological risk, particularly for the early life stages of aquatic animals., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Cystinuria (OMIM 220100) is an autosomal recessive hereditary disorder in which high urinary cystine excretion leads to the formation of cystine stones because of the low solubility of cystine at normal urinary pH. We developed clinical practice recommendation for diagnosis, surgical and medical treatment, and follow-up of patients with cystinuria. Elaboration of these clinical practice recommendations spanned from June 2018 to December 2019 with a consensus conference in January 2019. Selected topic areas were chosen by the co-chairs of the conference. Working groups focusing on specific topics were formed. Group members performed systematic literature review using MEDLINE, drafted the statements, and discussed them. They included geneticists, medical biochemists, pediatric and adult nephrologists, pediatric and adult urologists experts in cystinuria, and the Metabolic Nephropathy Joint Working Group of the European Reference Network for Rare Kidney Diseases (ERKNet) and eUROGEN members. Overall 20 statements were produced to provide guidance on diagnosis, genetic analysis, imaging techniques, surgical treatment (indication and modalities), conservative treatment (hydration, dietetic, alkalinization, and cystine-binding drugs), follow-up, self-monitoring, complications (renal failure and hypertension), and impact on quality of life. Because of the rarity of the disease and the poor level of evidence in the literature, these statements could not be graded. This clinical practice recommendation provides guidance on all aspects of the management of both adults and children with cystinuria, including diagnosis, surgery, and medical treatment., (Copyright © 2020 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

Introduction: The use of calcium load has been forgotten in pediatrics until recently whereas it is of utmost importance to have a practical approach to guide management of hypercalciuric nephrolithiasis., Objective: The purpose of this study was to evaluate the practical interest of oral calcium loads to improve the overall management of nephrolithiasis in children., Methods: We retrospectively studied all pediatric patients having undergone an oral calcium load in our pediatric nephrology unit between September 2015 and April 2017., Results: A total of 16 patients were included, at a median age of 12.0 (5.5-17.5) years. The indications of oral calcium load were: presence of an active urolithiasis without any obvious explanation after ruling out the "classical" biological abnormalities, or presence of hypercalciuria with stones composed of weddellite or carbapatite crystals. Among the 16 patients, 6 (38%) patients displayed absorptive hypercalciuria, 2 (12%) renal leak, 3 (19%) "unclassified" inadapted PTH, and 5 (31%) a normal calcium load test. The result of oral calcium load modified the clinical management in 14 (88%) patients, mainly based on the type of hypercalciuria. It allowed us to individualize nutritional advice: in patients with absorptive hypercalciuria, we proposed calcium intake within the lower normal range for age with dairy products not enriched with vitamin D, with the advice to avoid salt and calcium loads during evenings. Conversely, in patients with resorptive hypercalciuria, we proposed normal calcium intake for age. Showing the results of the calcium load is meaningful to patients and parents, and can be considered as an "educational" tool., Discussion: To the best of our knowledge, this study is the first to evaluate the interest of calcium load in children with nephrolithiasis in an era of routine PTH and 1-25-D assessment. Here, we demonstrate the feasibility and safety of oral calcium load in children, its interest to understand the underlying mechanisms of hypercalciuria, and its major interest as an "educational tool" for patients to explain them the underlying mechanisms and thus guide the therapeutic management using an individualized dietary approach. This study did not include many patients, but to the best of our knowledge, this is the first study evaluating and validating the feasibility of a safe and non-expensive diagnosis tool in pediatric hypercalciuria., Conclusion: Oral calcium load is helpful to guide therapeutic adaptation in pediatrics using an individualized dietary approach., (Copyright © 2020 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.)

Aim: The literature includes few reports on the prehospital care of pediatric casualties of urban house fires. Here we aimed to describe the epidemiology of pediatric fire victims, focusing on their injuries, prehospital care, and survival., Methods: This retrospective study included children under 15 years of age who were victims of urban house fires and who received care from prehospital medical teams. The variables analyzed included epidemiology, specific care provided by prehospital emergency services, the number of cardiac arrests, and survival rates., Results: Over the 15-month study period, 365 house fires required the presence of at least one prehospital medical team. Casualties of these fires included 121 pediatric victims (median age, 4 years [interquartile range: 2-9 years]). All children were initially treated by a prehospital medical team that was not specialized in pediatrics. Six children (4.9%) received secondary treatment from a pediatric support team. Of the 121 children, 114 (94.2%) suffered from smoke inhalation and seven (5.8%) from burns. Two patients who were in cardiac arrest at their initial medical care did not survive., Conclusion: Pediatric fire casualties were initially managed by prehospital medical teams that were not specialized in pediatrics. As in adults, the main injuries were secondary to smoke inhalation, but this has increased toxicity in children. Prehospital teams not specialized in pediatrics can optimize their practice via the sharing of experiences, team training, and cognitive aid checklist for pediatric fire victims., (Copyright © 2020. Published by Elsevier Masson SAS.)

The tentacular system of Clytia hemisphaerica medusa (Cnidaria, Hydrozoa) has recently emerged as a promising experimental model to tackle the developmental mechanisms that regulate cell lineage progression in an early-diverging animal phylum. From a population of proximal stem cells, the successive steps of tentacle stinging cell (nematocyte) elaboration, are spatially ordered along a "cellular conveyor belt". Furthermore, the C. hemisphaerica tentacular system exhibits bilateral organisation, with two perpendicular polarity axes (proximo-distal and oral-aboral). We aimed to improve our knowledge of this cellular system by combining RNAseq-based differential gene expression analyses and expression studies of Wnt signalling genes. RNAseq comparisons of gene expression levels were performed (i) between the tentacular system and a control medusa deprived of all tentacles, nematogenic sites and gonads, and (ii) between three samples staggered along the cellular conveyor belt. The behaviour in these differential expression analyses of two reference gene sets (stem cell genes; nematocyte genes), as well as the relative representations of selected gene ontology categories, support the validity of the cellular conveyor belt model. Expression patterns obtained by in situ hybridisation for selected highly differentially expressed genes and for Wnt signalling genes are largely consistent with the results from RNAseq. Wnt signalling genes exhibit complex spatial deployment along both polarity axes of the tentacular system, with the Wnt/β-catenin pathway probably acting along the oral-aboral axis rather than the proximo-distal axis. These findings reinforce the idea that, despite overall radial symmetry, cnidarians have a full potential for elaboration of bilateral structures based on finely orchestrated deployment of an ancient developmental gene toolkit., (Copyright © 2019. Published by Elsevier Inc.)

Rationale: Renal positron emission tomography (PET) functional imaging allows non-invasive and dynamic measurements of functional and metabolic parameters. [ 15 O]H 2 O is used as a perfusion tracer, and [ 11 C]acetate as an oxidative metabolism in this purpose, requiring two injections to assess those fundamental parameters. Yet, in cardiac physiology study, the high first-pass myocardial extraction fraction of [ 11 C]acetate allowed to use its influx rate as a blood flow marker too. Since [ 11 C]acetate has been characterized by a 20-25% single pass renal extraction in dogs, it could be used as a potential tracer for renal perfusion. The aim of this study was to determine whether [ 11 C]acetate influx rate can be used as quantitative in vivo marker of kidney perfusion in human., Methods: In 10 healthy subjects, dynamic PET acquisitions were performed after [ 15 O]H 2 O and [ 11 C]acetate injections spaced by a 15-minute interval. As previously validated, with compartmental modeling of kinetics, renal perfusion and oxidative metabolism were estimated respectively with influx rate of [ 15 O]H 2 O and efflux rate of [ 11 C]acetate. Additionally, influx rate of [ 11 C]acetate was regressed to influx rate of [ 15 O]H 2 O., Results: Renal time activity curves of [ 11 C]-acetate was best fitted with a mono compartmental model compared to a bi-compartmental model (p < 0.0001). [ 11 C]acetate influx rate was significantly correlated with perfusion quantified with [ 15 O]H 2 O (r 2  = 0.37, p < 0.001) at baseline. This regression allowed the computation of a renal [ 11 C]acetate extraction fraction (EF), and further the computation of renal blood flow from its influx rate., Conclusion: In healthy subjects, over a wide range of renal perfusion, direct estimates of renal oxygen consumption as well as tissue perfusion can be obtained by PET with a single tracer [ 11 C]acetate. This approach needs to be validated in CKD patients, and would be of great interest to design clinical protocol aiming at evaluating ischemic nephropathies candidate to revascularization., (Copyright © 2019 Elsevier Inc. All rights reserved.)

While direct measurements of glomerular filtration rate (GFR) provide the most accurate evaluation of pre-donation kidney function, guidelines do not systematically require the use of a reference method. We evaluated whether and to what extent relying upon creatinine-based estimating equations (eGFR) rather than direct measurement of GFR (mGFR) alters the selection of potential living donors. We compared the impact of 4 equations (the MDRD study equation, the CKD-EPI equation, the revised Lund-Malmö equation, and the full age spectrum [FAS] equation) on the evaluation of 2733 potential donors with GFR measured by reference methods. We also considered the impact of using either absolute or age-adapted GFR thresholds. The CKD-EPI and FAS equations had the best performances (P10 of 50.6% and 47.8%; P30 of 94.4% and 93.1%, respectively) and led to the lowest proportion of improperly evaluated candidates. Misclassification was more frequent when GFR adequacy was defined as an absolute threshold of 90 ml/min/1.73m 2 as compared to an age-adapted definition (26% and 5%, respectively). Interpretation of eGFR according to an absolute threshold of 90 ml/min/1.73m 2 identified 1804 candidates eligible to donate, compared to 2648 when mGFR was interpreted with age-adapted thresholds. We conclude that creatinine-based estimates cannot substitute for direct GFR measurement to evaluate candidates for kidney donation. When reference methods for direct GFR measurement are not available, our data suggest that a strategy based on age-adapted eGFR values estimated with either the CKD-EPI or FAS equation should be preferred., (Copyright © 2019 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

The epidemic of obesity parallels that of chronic kidney disease (CKD). Obesity worsens the course of CKD, mainly defined by an abnormal glomerular filtration rate (GFR). Patients with severe obesity stages (II and III with body mass index >35 kg/m 2 ) are eligible for bariatric surgery (BS), which is the most efficient method of achieving durable weight loss. BS may reverse glomerular hyperfiltration and albuminuria, improve adipocytokine profile, and relieve diabetes and hypertension. Obesity remission after BS might prevent the progression of renal failure in populations with morbid obesity. However, evidence for the beneficial effect of BS on renal function is scant. This lack of knowledge is mainly due to methodologic reasons, which are addressed in this review. The reversibility of hyperfiltration due to the presence of functional renal reserve hampers the interpretation of changes in true GFR after BS. This true GFR is only obtained with the renal clearance of an exogenous filtration marker. Estimation of GFR is generally provided by prediction equations, namely by modification of diet in renal diseases or by chronic kidney disease-epidemiology collaborative group. These equations are not accurate because the serum levels of both creatinine and cystatin C depend on extrarenal factors, which are modified by BS. Comparing the slopes of measured GFR according to various durations of exposure with morbid obesity would be critical in providing reliable data. Herein, we review the current knowledge on the effects of BS on kidney function; we specify the methodologic issues and particularities of the dietary management of CKD patients to propose reliable directions for future clinical research., (Copyright © 2018 American Society for Bariatric Surgery. Published by Elsevier Inc. All rights reserved.)

The present work is the first study investigating the impacts of chlordecone, an organochlorine insecticide, on the proteome of the decapod crustacean Macrobrachium rosenbergii, by gel-free proteomic analysis. The hepatopancreas protein expression variations were analysed in organisms exposed to three environmental relevant concentrations of chlordecone (i.e. 0.2, 2 and 20µg/L). Results revealed that 62 proteins were significantly up- or down-regulated in exposed prawns compared to controls. Most of these proteins are involved in important physiological processes such as ion transport, defense mechanisms and immune system, cytoskeleton dynamics, or protein synthesis and degradation. Moreover, it appears that 6% of the deregulated protein are involved in the endocrine system and in the hormonal control of reproduction or development processes of M. rosenbergii (e.g. vitellogenin, farnesoic acid o-methyltransferase). These results indicate that chlordecone is potentially an endocrine disruptor compound for decapods, as already observed in vertebrates. These protein modifications could lead to disruptions of M. rosenbergii growth and reproduction, and therefore of the fitness population on the long-term. Besides, these disrupted proteins could be suggested as biomarkers of exposure for endocrine disruptions in invertebrates. However, further investigations are needed to complete understanding of action mechanisms of chlordecone on proteome and endocrine system of crustaceans., (Copyright © 2017 Elsevier Inc. All rights reserved.)

The value of estimated glomerular filtration rate (eGFR) in living kidney donors screening is unclear. A recently published web-based application derived from large cohorts, but not living donors, calculates the probability of a measured GFR (mGFR) lower than a determined threshold. Our objectives were to validate the clinical utility of this tool in a cohort of living donors and to test two other strategies based on chronic kidney disease epidemiology collaboration (CKD-EPI) and on MDRD-eGFR. GFR was measured using 51 Cr- ethylene-diamine tetraacetic acid urinary clearance in 311 potential living kidney donors (178 women, mean age 50 ± 11.6 years). The web-based tool was used to predict those with mGFR < 80 mL/min/1.73 m 2 . Inputs to the application were sex, age, ethnicity, and plasma creatinine. In our cohort, a web-based probability of mGFR <90 mL/min/1.73 m 2 higher than 2% had 100% sensitivity for detection of actual mGFR <80 mL/min/1.73 m 2 . The positive predictive value was 0.19. A CKD-EPI-eGFR threshold of 104 mL/min/1.73 m 2 and an MDRD-eGFR threshold of 100 mL/min/1.73 m 2 had 100% sensitivity to detect donors with actual mGFR <80 mL/min/1.73 m 2 . We obtained similar results in an external cohort of 354 living donors. We confirm the usefulness of the web-based application to identify potential donors who should benefit from GFR measurement., (© Copyright 2016 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Myocardial conditioning is actually an essential strategy in the management of ischaemia-reperfusion injury. The concept of anaesthetic post-conditioning is intriguing, its action occurring at a pivotal moment (that of reperfusion when ischaemia reperfusion lesions are initiated) where the activation of these cardio-protective mechanisms could overpower the mechanisms leading to ischaemia reperfusion injuries. Desflurane and sevoflurane are volatile anaesthetics frequently used during cardiac surgery. This review focuses on the efficacy of desflurane and sevoflurane administered during early reperfusion as a potential cardio-protective strategy. In the context of experimental studies in animal models and in human atrial tissues in vitro, the mechanisms underlying the cardio-protective effect of these agents and their capacity to induce post-conditioning have been reviewed in detail, underlining the role of reactive oxygen species generation, the activation of the cellular signalling pathways, and the actions on mitochondria along with the translatable actions in humans; this might well be sufficient to set the basis for launching randomized clinical studies, actually needed to confirm this strategy as one of real impact., (© The Author 2016. Published by Oxford University Press on behalf of the British Journal of Anaesthesia. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Surface sediment and oysters (Crassostrea rhizophorae) from the coastlines of Guadeloupe were analysed for polycyclic aromatic hydrocarbons (PAHs) using GC/MS. Biomarkers of oxidative stress were used to assess the response of these oysters to hydrocarbons exposure. The total concentration of PAHs in the sediment ranged from 49 to 1065 ng/g dw, while concentrations in oyster ranged from 66 to 961 ng/g dw. Molecular indices based on isomeric PAHs ratios characterize the pollution sources and show that most of the contaminations in sediment originate from pyrolytic inputs. Bioaccumulation factors (BAFs) have been related to isomeric ratio calculated for oysters in order to refine PAHs sources. The variations of BAFs observed in the different compounds resulted from different uptake pathways in the mangrove oysters according to the type of inputs. Response of biomarkers showed inhibition of catalase and an increase of lipid peroxidation at the station where PAHs concentrations were the highest. Taken together, data obtained point to the relevance of considering environmental conditions as factors influencing biomarker responses in environmental monitoring programs. These data also indicate the need for regular environmental follow-up studies in Guadeloupe., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Mature dendritic cells (DCs) are stimulators of T-cell immune response, whereas immature DCs support T-cell tolerance. Murine B cells can inhibit the production of IL-12 by DCs and thereby hinder the inflammatory response. Notwithstanding the importance of this modulation, only a few studies are available in humans. Here, we have developed an in vitro model of cocultures to assess its significance. We establish that human activated B cells restrained the development of monocytes into immature DCs and their differentiation into mature DCs. In addition, they decreased the density of HLA-DR from mature DCs, the expression of CD80 and CD86 coactivation molecules, the production of IL-12p70 required for antigen presentation and Th1 differentiation, and inhibited the DC-induced T-cell proliferation. These modulations were mediated by CD19(+)IgD(low)CD38(+)CD24(low)CD27(-) B cells and needed direct cell-to-cell contacts that involved CD62L for the control of CD80 and CD86 expression and a soluble factor for the control of IL-12 production. Moreover, mature DCs from patients with systemic lupus erythematosus displayed insensitivity to the regulation of IL-12. Overall, it appears that human B cells can regulate DC maturation and function and that inefficient B-cell regulation may influence an improper balance between an effector inflammatory response and tolerance induction.

Background: Desflurane triggers post-conditioning in the diabetic human myocardium. We determined whether protein kinase C (PKC), mitochondrial adenosine triphosphate-sensitive potassium (mitoK(ATP)) channels, Akt, and glycogen synthase kinase-3β (GSK-3β) were involved in the in vitro desflurane-induced post-conditioning of human myocardium from patients with type 2 diabetes., Methods: The isometric force of contraction (FoC) of human right atrial trabeculae obtained from patients with type 2 diabetes was recorded during 30 min of hypoxia followed by 60 min of reoxygenation. Desflurane (6%) was administered during the first 5 min of reoxygenation either alone or in the presence of calphostin C (PKC inhibitor) or 5-hydroxydecanoate (5-HD) (mitoK(ATP) channel antagonist). Phorbol 12-myristate 13-acetate (PKC activator) and diazoxide (a mitoK(ATP) channel opener) were superfused during early reoxygenation. The FoC at the end of the 60 min reoxygenation period was compared among treatment groups (FoC(60); mean and sd). The phosphorylation of Akt and GSK-3β was studied using western blotting., Results: Desflurane enhanced the recovery of force [FoC(60): 79 (3)% of baseline] after 60 min of reoxygenation when compared with the control group (P>0.0001). Calphostin C and 5-HD abolished the beneficial effect of desflurane-induced post-conditioning (both P<0.0001). Phorbol 12-myristate 13-acetate and diazoxide enhanced the FoC(60) when compared with the control group (both P<0.0001). Desflurane increased the level of phosphorylation of Akt and GSK-3β (P<0.0001)., Conclusions: Desflurane-induced post-conditioning in human myocardium from patients with type 2 diabetes was mediated by the activation of PKC, the opening of the mitoK(ATP) channels, and the phosphorylation of Akt and GSK-3β.

Purpose: The echocardiographic assessment of right ventricular (RV) function requires many different parameters. We studied and compared with magnetic resonance imaging (MRI) two markers of RV function derived from new imaging tools: 2D speckle imaging (2DSI) and three dimensional echography., Methods and Results: Thirty-two patients (19 with RV ejection fraction [RVEF]< or =45%) underwent both complete echocardiography--including standard parameters of RV function (fractional area change [FAC], Tei index, systolic velocity of tricuspid annulus by DTI), 3D full-volume acquisition on RV--and MRI for the evaluation of RV volumes and RVEF. 2DSI was applied to high frame rate cine loops centred on the RV free wall with measurement of peak systolic strain (%) in the basal, median and apical segments of this wall. Strain, especially in RV median and apical segments, is reduced in patients with RVEF less or equal to 45% (median strain: -16.39+/-5.27 vs. -24.74+/-8.00 [p=0.002]; apical strain -13.01+/-6.84 vs. 22.53+/-11.32 [p=0.03]) with a very good correlation with RVEF (r=-0.717, p=0.0001) but also with the usual echographic parameters of RV function, (FAC: r=0.019; Tei: r=0.01; peak systolic velocity: r=0.002). The 3D RVEF is also but poorly correlated with MRI RVEF, (r=0.447, p=0.017). Furthermore, 3D significantly underestimated RV volumes. By multivariate analysis, apical strain (p=0.004) and FAC (p=0.029) were predictive of a decreased RVEF., Conclusion: Apical strain as measured from 2DSI seems a promising parameter in the estimation of RV function. 3D estimation of RVEF is more disappointing because of an important underestimation of RV volumes.

We report the case of a patient who was admitted for acute coronary syndrom associated with fever originating from urinary tract. Coronary arteriography revealed a huge coronary aneurysm which ruptured a short time after diagnosis. After surgery, it was proven to be mycotic aneurysm related to Escherichia Coli sepsis.

Mitochondrial DNA integrity is ensured by several nuclear-encoded proteins in vertebrates, and a number of mtDNA alterations in human diseases, including deletions and duplications, have been suspected to result from errors in the mitochondrial recombination pathway. However, the presence of the latter system is still a matter of controversy as RecA proteins display various functions in vitro. In Escherichia coli, RecA plays a central role in homologous recombination by pairing and transferring a single strand to a homologous duplex DNA. To address indirectly the issue of a mitochondrial recombination pathway in vivo, we have constructed a chimeric gene containing an N terminal mitochondrial targeting sequence and the E. coli RecA gene. Cells were transfected by the recombinant plasmid, then tested for their mtDNA repair upon bleomycin treatment. We found an increased repair rate of the mitochondrial DNA in cells expressing RecA as compared to control cells. These results indicate that the transfected cells display an improved mtDNA repair replication pathway due to the exogenous RecA, likely in synergy with an endogenous rate-limiting mitochondrial recombination pathway.

Oxidation of sucrose by the NaOCl/TEMPO system provided sucrose tricarboxylate without the addition of sodium bromide as co-catalyst when high-frequency (500 kHz) ultrasound was applied, in contrast to very limited conversion without sonication. In the presence of sodium bromide, sonication also caused acceleration of the oxidation. The rate increase due to sonication of the oxidant system prior to sucrose addition suggests that ultrasound acts at the level of the formation of the nitrosonium ion, the active oxidising species in the catalytic cycle.