Ancestral light and chloroplast regulation form the foundations for C4 gene expression.

C4 photosynthesis acts as a carbon concentrating mechanism that leads to large increases in photosynthetic efficiency. The C4 pathway is found in more than 60 plant lineages1 but the molecular enablers of this evolution are poorly understood. In particular, it is unclear how non-photosynthetic proteins in the ancestral C3 system have repeatedly become strongly expressed and integrated into photosynthesis gene regulatory networks in C4 leaves. Here, we provide clear evidence that in C3 leaves, genes encoding key enzymes of the C4 pathway are already co-regulated with photosynthesis genes and are controlled by both light and chloroplast-to-nucleus signalling. In C4 leaves this regulation becomes increasingly dependent on the chloroplast. We propose that regulation of C4 cycle genes by light and the chloroplast in the ancestral C3 state has facilitated the repeated evolution of the complex and convergent C4 trait.The work was funded by the European Union 3to4 project and Biotechnology and Biological Sciences Research Council (BBSRC) grant BB/J011754/1. I.G.-M. was supported by the Amgen Foundation. Research on chloroplast signalling by M.J.T. was supported by BBSRC grant (BB/J018139/1).This is the author accepted manuscript. The final version is available from the Nature Publishing Group via http://dx.doi.org/10.1038/nplants.2016.16

High-flow oxygen therapy versus noninvasive ventilation: a randomised physiological crossover study of alveolar recruitment in acute respiratory failure.

High-flow nasal cannula (HFNC) oxygen therapy has recently shown clinical benefits in hypoxaemic acute respiratory failure (ARF) patients, while the value of noninvasive ventilation (NIV) remains debated. The primary end-point was to compare alveolar recruitment using global end-expiratory electrical lung impedance (EELI) between HFNC and NIV. Secondary end-points compared regional EELI, lung volumes (global and regional tidal volume variation (V (T))), respiratory parameters, haemodynamic tolerance, dyspnoea and patient comfort between HFNC and NIV, relative to face mask (FM). A prospective randomised crossover physiological study was conducted in patients with hypoxaemic ARF due to pneumonia. They received alternately HFNC, NIV and FM. 16 patients were included. Global EELI was 4083 with NIV and 2921 with HFNC (p=0.4). Compared to FM, NIV and HFNC significantly increased global EELI by 1810.5 (95% CI 857-2646) and 826 (95% CI 399.5-2361), respectively. Global and regional V (T) increased significantly with NIV compared to HFNC or FM, but not between HFNC and FM. NIV yielded a significantly higher pulse oxygen saturation/inspired oxygen fraction ratio compared to HFNC (p=0.03). No significant difference was observed between HFNC, NIV and FM for dyspnoea. Patient comfort score with FM was not significantly different than with HFNC (p=0.1), but was lower with NIV (p=0.001). This study suggests a potential benefit of HFNC and NIV on alveolar recruitment in patients with hypoxaemic ARF. In contrast with HFNC, NIV increased lung volumes, which may contribute to overdistension and its potentially deleterious effect in these patients

[Kidney disease in cobalamin C deficiency].

International audienceCobalamin C deficiency (cblC) is the most common inborn error of vitamin B12 metabolism. This autosomal recessive disease is due to mutations in MMACHC gene, encoding a cyanocobalamin decyanase. It leads to hyperhomocysteinemia associated with hypomethioninemia and methylmalonic aciduria. Two distinct phenotypes have been described : early-onset forms occur before the age of one year and are characterized by a severe multisystem disease associating failure to thrive to neurological and ophthalmological manifestations. They are opposed to late-onset forms, less severe and heterogeneous. CblC deficiency-associated kidney lesions remain poorly defined. Thirty-eight cases have been described. Age at initial presentation varied from a few days to 28 years. Most of the patients presented renal thrombotic microangiopathy (TMA) associated with acute renal failure, and 21 patients presented typical lesions of renal thrombotic microangiopathy on kidney biopsy. Prognosis was poor, leading to death in the absence of treatment, and related to the severity of renal lesions in the early-onset forms. Late-onset disease had better prognosis and most of patients were weaned off dialysis after treatment initiation. We suggest that all the patients with renal TMA be screened for cobalamin metabolism disorder, regardless of age and even in the absence of neurological symptoms, to rapidly initiate the appropriate treatment

Monitoring of hemodialysis quality-of-care indicators: why is it important?

International audienceBACKGROUND: Meeting specific guideline targets is associated with improved survival rates and reduced hospitalizations in the dialysis population. This prospective work evaluated the adequacy of hemodialysis quality indicators in an in-center hemodialysis population with severe comorbidities, and assessed whether clinical practice could impact intermediate outcomes. METHODS: All the chronic hemodialysis patients treated in Rouen University Hospital hemodialysis Unit between January 2009 and April 2010 were included in this observational study. Every quarter, mean levels and prevalence of conformity were collected for the following indicators: anemia, dialysis dose, serum calcium and phosphorus, PTH, 25OH-vitamin D, albumin, serum bicarbonate, LDL-cholesterol, serum beta2-microglobulin, systolic and diastolic blood pressure, intradialytic hypotension and vascular access. Conformity of quality-of-care indicators was determined according to targets defined by international guidelines, whenever available. RESULTS: Altogether, 124 patients were included in the study. Thirty-three patients were evaluated during the entire follow-up period. An improvement in the percentage of conformity was observed for hemoglobin, dialysis dose, phosphates, PTH, serum bicarbonate and beta2-microglobulin in the global population. Failure to improve conformity rates for several indicators, including serum albumin, was found, possibly depending on patients' comorbidities rather than on quality of care. CONCLUSION: Overall, this study shows that following quality-of-care indicators can improve clinical practice by identifying center-specific weaknesses, prompting the establishment of corrective measures. Finally, we suggest that the definition and targets of some indicators, especially hypertension and LDL-cholesterol, be reviewed, since evidence of their association with mortality is not demonstrated

Thrombotic microangiopathy associated with anticancer and immune system targeting drugs: New insights from real-world data using the WHO pharmacovigilance database

International audienceAbstract Background The worldwide development of immune system targeting/anticancer drugs has revolutionized immuno‐oncology, but their implication in thrombotic microangiopathy syndromes (TMA) is increasingly suspected. Using real‐world data, the aim of this study was to identify drugs associated with TMA reporting and to describe the evolution of TMA reporting over time with a focus on these drugs. Methods A global disproportionality study was performed using the individual case safety reports (ICSRs) extracted from the World Health Organization (WHO) pharmacovigilance database (VigiBase) from its inception (1968) to April 30, 2022. Results Of the 31,251,040 ICSRs, 6946 cases of suspected drug‐induced TMA were included from 55 countries. The outcome was fatal in 18.2% of cases. A total of 72 immune system targeting/anticancer drugs were associated with significant overreporting, including 17 drugs with a potential new safety concern for TMA. Although the rate of TMA reporting per million of ICSRs has remained fairly stable, an absolute increase in reported cases of suspected drug‐induced TMA has been observed over the last decade. The pattern of drugs reported in TMA has evolved with a substantial increase in the proportion of cases involving immune system‐targeting drugs/anticancer drugs from 47.3% (205/433) in the period 1992–2001 to 80.7% (3819/4730) in the period 2012–2021. Conclusion Several recently marketed immune system targeting/anticancer drugs have been identified as potential new drugs associated with TMA, which will require confirmatory studies. The number of drugs associated with TMA reporting markedly increased within the past 10 years, primarily due to innovative anticancer drugs

Adrenocortical carcinoma complicated by renal thrombotic microangiopathy, a case-series

International audienceBackground: Cancer-related thrombotic microangiopathy (CR-TMA) is a rare entity associated with a dismal prognosis. Usually, CR-TMA is associated with mucin-producing carcinomas among which stomach, breast, prostate, lung and pancreas tumours are the most frequent. Cases presentation: We describe for the first time three cases of CR-TMA due to adrenocortical carcinoma (ACC). All of them had mechanical hemolytic anemia and thrombocytopenia without any other identifiable cause. Bicytopenia was diagnosed either simultaneously with ACC or at the time of metastatic evolution. Two patients had acute kidney injury (AKI) with severe pathological findings on kidney biopsy. Despite total adrenalectomy, chemotherapy, and specific treatment of TMA with plasma-exchanges, renal failure and hemolytic anemia remained. The only manifestation of CR-TMA in the third patient was hemolytic anemia, which resolved after surgical removal of ACC. The evolutions in these patients suggests ACC-related TMA may be related to a circulating factor. Conclusions: CR-TMAs are rare. Here we describe the first case series of ACC-related TMA, among which two had renal involvement. This entity is associated with dismal renal prognosis despite specific treatment of TMA. According to patients' evolution, the persistence of TMA may reflect an uncontrolled malignancy

Recommandations ESUR sur l’utilisation des produits de contraste : enquête de pratique, revue et commentaire par le CJN, le FIRN et la SFNDT

International audienceContrast media administration is classically considered to cause or worsen kidney failure. Recent data may moderate this assertion. The European Society of Urogenital Radiology recently published guidelines re-evaluating the precautions before administering contrast media. The present work evaluates the practice of French nephrologists, and provides a commentary on these recommendations based on an updated review of the literature. We conducted survey among French nephrologists, using an electronic questionnaire distributed by the Societe Francophone de Nephrologie, Dialyse et Transplantation, the French Intensive care Renal Network and the Club des Jeunes Nephrologues. 266 responses were collected. The European Society of Urogenital Radiology guidelines are poorly known among the panel of nephrologists. Their practices differ from the guidelines by the more frequent and earlier implementation of measures to prevent renal failure post contrast media. In accordance with the guidelines, hydration is prescribed as a first-line preventive measure, mainly with saline and bicarbonate. Inhibitors of the renin-angiotensin-aldosterone system are frequently discontinued before an injection of contrast media, contrary to what is recommended. In conclusion, the European Society of Urogenital Radiology guidelines, which the working group endorses, but which are still too little known and applied in clinical nephrology in France, prompt nephrologists to lift some of the restrictions on the use of PCI as well as on the continuation of ARS inhibitors before injecting PCI. (C) 2020 Societe francophone de nephrologie, dialyse et transplantation.L’injection d’un produit de contraste iodé est classiquement considérée comme un facteur de l’apparition ou de l’aggravation d’une insuffisance rénale. Des données récentes viennent cependant tempérer cette opinion. L’European Society of Urogenital Radiology a récemment publié des recommandations réévaluant les précautions à prendre avant l’administration de produits de contraste. Ce travail propose une évaluation des pratiques des néphrologues français et un commentaire de ces recommandations fondé sur une revue de la littérature. Nous avons mené une enquête de pratique par voie électronique, par l’intermédiaire d’un questionnaire électronique diffusé par la société francophone de néphrologie, dialyse et transplantation, le French Intensive care Renal Network et le club des jeunes néphrologues. Nous avons obtenu 266 réponses. Les recommandations de l’European Society of Urogenital Radiology sont peu connues du panel de néphrologues interrogés. Les pratiques rapportées diffèrent de ces recommandations par la mise en place plus fréquente, et pour un stade moins avancé d’insuffisance rénale chronique, de mesures de prévention de l’insuffisance rénale post-produit de contraste iodé. Conformément aux recommandations, l’hydratation est utilisée en première intention, principalement par soluté salé isotonique et bicarbonate de sodium. Les inhibiteurs du système rénine-angiotensine-aldostérone sont fréquemment arrêtés avant une injection de produit de contraste, contrairement à ce qui est préconisé. En conclusion, les nouvelles recommandations de l’European Society of Urogenital Radiology, que le groupe de travail fait siennes, mais qui sont encore trop peu connues et appliquées en néphrologie clinique en France, incitent les néphrologues à lever certaines des restrictions à l’utilisation des produits de contraste iodés ainsi qu’à la poursuite des inhibiteurs du système rénine-angiotensine-aldostérone avant l’injection des produits de contraste iodés

Kidney and contrast media: Common viewpoint of the French Nephrology societies (SFNDT, FIRN, CJN) and the French Radiological Society (SFR) following ESUR guidelines

International audienceContrast medium administration is classically considered to cause or worsen kidney failure, but recent data may moderate this assertion. The European Society of Urogenital Radiology recently published guidelines re-evaluating the precautions before administering contrast media. Kidney injury does not constitute a contra-indication to the administration of iodinated contrast medium, as long as the benefit-risk ratio justifies it. Intravenous hydration with 0.9% NaCl or 1.4% sodium bicarbonate is the only validated measure for the prevention of post-iodine contrast nephropathy. This is necessary for intravenous or intra-arterial administration of iodinated contrast agent without first renal pass when the glomerular filtration rate is less than 30 mL/min/1.73 m(2), for intra-arterial administration of iodinated contrast agent with first renal passage when the glomerular filtration rate is less than 45 mL/min/1.73 m(2), or in patients with acute renal failure. The use of iodinated contrast medium should allow the carrying out of relevant examinations based on an analysis of the benefit-risk ratio and the implementation of measures to prevent toxicity when necessary. (C) 2021 Societe francaise de radiologie

Gene Expression of Protein Tyrosine Phosphatase 1B and Endoplasmic Reticulum Stress During Septic Shock

International audienceIntroduction: Protein Tyrosine Phosphatase 1B (PTP1B) and endoplasmic reticulum stress (ERS) are involved in the septic inflammatory response. Their inhibition is associated with improved survival in murine models of sepsis. The objective was to describe PTP1B and ERS expression during septic shock in human. Material and Methods: Prospective study including patients admitted to intensive care unit (ICU) for septic shock. Blood samples were collected on days 1 (D1), 3 and 5 (D5). Quantitative PCR (performed from whole blood) evaluated the expression of genes coding for PTP1B (PTPN1) and key elements of ERS (GRP78, ATF6, CHOP) or for endothelial dysfunction-related markers (ICAM1 and ET1). We analyzed gene variation between D5 and D1, collected glycemic parameters, insulin resistance and organ failure was evaluated by Sequential Organ Failure Assessment (SOFA) score. Results: We included 44 patients with a mean SAPS II 50 ± 16 and a mortality rate of 13.6%. Between D1 and D5, there was a significant decrease of PTPN1 (p < 0.001) and ATF6 (p < 0.001) expressions. Their variations of expression were correlated with SOFA variation (PTPN1, r = 0.35, CI 95% [0.05; 0.54], p = 0.03 and ATF6, r = 0.45 CI 95% [0.20; 0.65], p < 0.001). We did not find any correlation between PTPN1 expression and insulin resistance or glycemic parameters. Between D1 and D5, ATF6 and PTPN1 expressions were correlated with that of ET1. Conclusions: Our study has evaluated for the first time the expression of PTP1B and ERS in patients with septic shock, revealing that gene expression variation of PTPN1 and ATF6 are partly correlated with the evolution of septic organ failure and with endothelial dysfunction markers expression