Soluble tumor necrosis factor receptor 1 and 2 predict outcomes in advanced chronic kidney disease : a prospective cohort study

Background : Soluble tumor necrosis factor receptors 1 (sTNFR1) and 2 (sTNFR2) have been associated to progression of renal failure, end stage renal disease and mortality in early stages of chronic kidney disease (CKD), mostly in the context of diabetic nephropathy. The predictive value of these markers in advanced stages of CKD irrespective of the specific causes of kidney disease has not yet been defined. In this study, the relationship between sTNFR1 and sTNFR2 and the risk for adverse cardiovascular events (CVE) and all-cause mortality was investigated in a population with CKD stage 4-5, not yet on dialysis, to minimize the confounding by renal function. Patients and methods : In 131 patients, CKD stage 4-5, sTNFR1, sTNFR2 were analysed for their association to a composite endpoint of all-cause mortality or first non-fatal CVE by univariate and multivariate Cox proportional hazards models. In the multivariate models, age, gender, CRP, eGFR and significant comorbidities were included as covariates. Results : During a median follow-up of 33 months, 40 events (30.5%) occurred of which 29 deaths (22.1%) and 11 (8.4%) first non-fatal CVE. In univariate analysis, the hazard ratios (HR) of sTNFR1 and sTNFR2 for negative outcome were 1.49 (95% confidence interval (CI): 1.28-1.75) and 1.13 (95% CI: 1.06-1.20) respectively. After adjustment for clinical covariables (age, CRP, diabetes and a history of cardiovascular disease) both sTNFRs remained independently associated to outcomes (HR: sTNFR1: 1.51, 95% CI: 1.30-1.77; sTNFR2: 1.13, 95% CI: 1.06-1.20). A subanalysis of the non-diabetic patients in the study population confirmed these findings, especially for sTNFR1. Conclusion : sTNFR1 and sTNFR2 are independently associated to all-cause mortality or an increased risk for cardiovascular events in advanced CKD irrespective of the cause of kidney disease

N-type organic thermoelectrics : demonstration of ZT > 0.3

The 'phonon-glass electron-crystal' concept has triggered most of the progress that has been achieved in inorganic thermoelectrics in the past two decades. Organic thermoelectric materials, unlike their inorganic counterparts, exhibit molecular diversity, flexible mechanical properties and easy fabrication, and are mostly 'phonon glasses'. However, the thermoelectric performances of these organic materials are largely limited by low molecular order and they are therefore far from being 'electron crystals'. Here, we report a molecularly n-doped fullerene derivative with meticulous design of the side chain that approaches an organic 'PGEC' thermoelectric material. This thermoelectric material exhibits an excellent electrical conductivity of >10Scm(-1) and an ultralow thermal conductivity of 0.3 for organic thermoelectrics

Coccolithophorid calcium carbonate dissolution in surface waters

The role of calcifying organisms in the ocean biogeochemistry has been receiving increasing attention since CO2-related global change issues such as ocean acidification were pointed out by the scientific community. The implications of changing oceanic pH in modifying ecosystems dominated by planktonic calcifiers have been shown by mesocosm and laboratory experiments based on CO2 manipulations. The major concern of such experiments focussed on variations in the rates of ecosystem primary production and calcification due to changes in algal physiology or specific composition. Our results, from an interdisciplinary survey of coccolithophore-dominated blooms in the northern Bay of Biscay (NE Atlantic), suggest that biogenic calcite dissolution is occurring in the photic zone where surface waters are oversaturated with respect to calcite. The dissolution of CaCO3 in surface waters, evidenced by scanning electron microscopy observations, has an impact on the preservation and export of carbon in coccolithophore-dominated ecosystems and on the exchange of CO2 across the ocean-atmosphere interface. Both aspects of suspended calcite concentration reduction in natural environments (lower rates of production or dissolution) could be considered as a perturbation of the oceanic carbon cycle. We aim at presenting here a biogeochemical description of processes, including integrated primary production, calcification, and parameters such as transparent exopolymer particles concentration and particulate inorganic carbon profiles, during field studies. A mechanism for calcite dissolution, based on biological activity in microenvironments (including grazing, bacterial respiration and DMS production) is presented as a conceptual model in coccolithophore blooms

Loss of DPP6 in neurodegenerative dementia : a genetic player in the dysfunction of neuronal excitability

Emerging evidence suggested a converging mechanism in neurodegenerative brain diseases (NBD) involving early neuronal network dysfunctions and alterations in the homeostasis of neuronal firing as culprits of neurodegeneration. In this study, we used paired-end short-read and direct long-read whole genome sequencing to investigate an unresolved autosomal dominant dementia family significantly linked to 7q36. We identified and validated a chromosomal inversion of ca. 4Mb, segregating on the disease haplotype and disrupting the coding sequence of dipeptidyl-peptidase 6 gene (DPP6). DPP6 resequencing identified significantly more rare variants-nonsense, frame-shift, and missense-in early-onset Alzheimer's disease (EOAD, p value = 0.03, OR = 2.21 95% CI 1.05-4.82) and frontotemporal dementia (FTD, p = 0.006, OR = 2.59, 95% CI 1.28-5.49) patient cohorts. DPP6 is a type II transmembrane protein with a highly structured extracellular domain and is mainly expressed in brain, where it binds to the potassium channel K(v)4.2 enhancing its expression, regulating its gating properties and controlling the dendritic excitability of hippocampal neurons. Using in vitro modeling, we showed that the missense variants found in patients destabilize DPP6 and reduce its membrane expression (p < 0.001 and p < 0.0001) leading to a loss of protein. Reduced DPP6 and/or K(v)4.2 expression was also detected in brain tissue of missense variant carriers. Loss of DPP6 is known to cause neuronal hyperexcitability and behavioral alterations in Dpp6-KO mice. Taken together, the results of our genomic, genetic, expression and modeling analyses, provided direct evidence supporting the involvement of DPP6 loss in dementia. We propose that loss of function variants have a higher penetrance and disease impact, whereas the missense variants have a variable risk contribution to disease that can vary from high to low penetrance. Our findings of DPP6, as novel gene in dementia, strengthen the involvement of neuronal hyperexcitability and alteration in the homeostasis of neuronal firing as a disease mechanism to further investigate

Genomic investigations of unexplained acute hepatitis in children

Since its first identification in Scotland, over 1,000 cases of unexplained paediatric hepatitis in children have been reported worldwide, including 278 cases in the UK1. Here we report an investigation of 38 cases, 66 age-matched immunocompetent controls and 21 immunocompromised comparator participants, using a combination of genomic, transcriptomic, proteomic and immunohistochemical methods. We detected high levels of adeno-associated virus 2 (AAV2) DNA in the liver, blood, plasma or stool from 27 of 28 cases. We found low levels of adenovirus (HAdV) and human herpesvirus 6B (HHV-6B) in 23 of 31 and 16 of 23, respectively, of the cases tested. By contrast, AAV2 was infrequently detected and at low titre in the blood or the liver from control children with HAdV, even when profoundly immunosuppressed. AAV2, HAdV and HHV-6 phylogeny excluded the emergence of novel strains in cases. Histological analyses of explanted livers showed enrichment for T cells and B lineage cells. Proteomic comparison of liver tissue from cases and healthy controls identified increased expression of HLA class 2, immunoglobulin variable regions and complement proteins. HAdV and AAV2 proteins were not detected in the livers. Instead, we identified AAV2 DNA complexes reflecting both HAdV-mediated and HHV-6B-mediated replication. We hypothesize that high levels of abnormal AAV2 replication products aided by HAdV and, in severe cases, HHV-6B may have triggered immune-mediated hepatic disease in genetically and immunologically predisposed children

Uroscanner (évaluation d'une acquisition unique mixte néphrographique et excrétoire dans l' hématurie indolore)

Évaluer une acquisition unique néphrographique et excrétoire dans l hématurie indolore. Étude prospective de 68 patients présentant une hématurie indolore. Le protocole incluait au minimum 3 phases (sans injection, cortico-médullaire, et mixte néphrographique et excrétoire). L acquisition d une phase plus tardive a été réalisée en cas d opacification jugée insuffisante.L analyse exclusive des phases mixte et tardive a été réalisée de façon indépendante par 3 radiologues.La comparaison a été faite avec le compte rendu réalisé sur la lecture de la totalité des phases d acquisition. Chez 31 patients (44,5%), aucune anomalie n a été retrouvée. Trente sept calculs, 23 lésions vésicales, 4 lésions urétérales, et 4 lésions rénales ont été détectés. La phase unique, complétée dans 25 cas (37%) par une phase tardive, a montré une sensibilité de 73 à 84% pour la détection des calculs, de 91 à 100% pour les lésions vésicales, de 100% pour les lésions urétérales et rénales. L utilisation de cette phase unique réduit de 60% l irradiation du patient. La phase mixte unique représente une alternative séduisante au protocole multiphase dans l exploration d une hématurie, permettant une réduction significative de l irradiation. La détection de calcul reste une limite pour laquelle une phase sans injection basse dose pourrait être réalisée en complément.PARIS6-Bibl.Pitié-Salpêtrie (751132101) / SudocSudocFranceF

Phosphorus and nitrogen speciation, transformation and retention in the Scheldt estuary (Belgium/The Netherlands) from the freshwater tidal limits to the North Sea

info:eu-repo/semantics/publishe

Dissolved Inorganic Carbon dynamics in the northern Bay of Biscay during a Coccolithophore bloom

In the framework of the Belgian global change programme, we have developed a project devoted to the study of the inorganic carbon cycle in the Bay of Biscay where coccolithophore blooms occur frequently. The study focuses on processes associated with the oceanic production and dissolution of calcium carbonate and related CO2 fluxes. Real time remote sensing allowed to localize the coccolithophore bloom that the R.V. Belgica visited in June 2004 during a multidisciplinary scientific cruise. We will present vertical profiles of pH, Talk, along with other parameters (salinity, temperature, chlorophyll a and phaeopigments) and 14C incorporation experiments. Inorganic carbon fluxes will be discussed in the photic zone, in correlation with the biological activity of phytoplankton (biological and carbonate pumps)