High-sensitivity versus conventional troponin in the emergency department for the diagnosis of acute myocardial infarction

International audienceINTRODUCTION: Recently, newer assays for cardiac troponin (cTn) have been developed which are able to detect changes in concentration of the biomarker at or below the 99th percentile for a normal population. The objective of this study was to compare the diagnostic performance of a new high-sensitivity troponin T (HsTnT) assay to that of conventional cTnI for the diagnosis of acute myocardial infarction (AMI) according to pretest probability (PTP). METHODS: In consecutive patients who presented to our emergency departments with chest pain suggestive of AMI, levels of HsTnT were measured at presentation, blinded to the emergency physicians, who were asked to estimate the empirical PTP of AMI. The discharge diagnosis was adjudicated by two independent experts on the basis of all available data. RESULTS: A total of 317 patients were included, comprising 149 (47%) who were considered to have low PTP, 109 (34%) who were considered to have moderate PTP and 59 (19%) who were considered to have high PTP. AMI was confirmed in 45 patients (14%), 22 (9%) of whom were considered to have low to moderate PTP and 23 (39%) of whom were considered to have high PTP (P < 0.001). In the low to moderate PTP group, HsTnT levels ≥ 0.014 μg/L identified AMI with a higher sensitivity than cTnI (91%, 95% confidence interval (95% CI) 79 to 100, vs. 77% (95% CI 60 to 95); P = 0.001), but the negative predictive value was not different (99% (95% CI 98 to 100) vs. 98% (95% CI 96 to 100)). There was no difference in area under the receiver operating characteristic (ROC) curve between HsTnT and cTnI (0.93 (95% CI 0.90 to 0.98) vs. 0.94 (95% CI 0.88 to 0.97), respectively). CONCLUSIONS: In patients with low to moderate PTP of AMI, HsTnT is slightly more useful than cTnI. Our results confirm that the use of HsTnT has a higher sensitivity than conventional cTnI

Vasopressin, ATP and catecholamines differentially control potassium secretion in inner ear cell line.

International audienceA strict control of endolymph composition (high potassium, low sodium fluid) and volume is instrumental for a proper functioning of the inner ear. Alteration of endolymph homeostasis is proposed in the pathogenesis of Menière's disease. However, the mechanisms controlling endolymph secretion remain elusive. By using the vestibular EC5v cells, we provide evidence for the presence of vasopressin, catecholamine and purinergic signaling pathways, coupled to adenylate cyclase, phosphoinositidase C and Ca(2+) activation. We demonstrate that vasopressin and catecholamines stimulate while ATP inhibits apical potassium secretion by EC5v cells. These results open new interesting perspectives for the management of inner ear diseases

Value of high-sensitivity C-reactive protein for classification of early axial spondyloarthritis: results from the DESIR cohort.

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Pby1 is a direct partner of the Dcp2 decapping enzyme

International audienceMost eukaryotic mRNAs harbor a characteristic 5 m 7 GpppN cap that promotes pre-mRNA splicing, mRNA nucleocytoplasmic transport and translation while also protecting mRNAs from exonucleolytic attacks. mRNA caps are eliminated by Dcp2 during mRNA decay, allowing 5-3 exonucleases to degrade mRNA bodies. However, the Dcp2 decapping enzyme is poorly active on its own and requires binding to stable or transient protein partners to sever the cap of target mRNAs. Here, we analyse the role of one of these partners, the yeast Pby1 factor, which is known to co-localize into P-bodies together with decapping factors. We report that Pby1 uses its C-terminal domain to directly bind to the decapping enzyme. We solved the structure of this Pby1 domain alone and bound to the Dcp1-Dcp2-Edc3 de-capping complex. Structure-based mutant analyses reveal that Pby1 binding to the decapping enzyme is required for its recruitment into P-bodies. Moreover, Pby1 binding to the decapping enzyme stimulates growth in conditions in which decapping activation is compromised. Our results point towards a direct connection of Pby1 with decapping and P-body formation , both stemming from its interaction with the Dcp1-Dcp2 holoenzyme

Aldosterone-signaling defect exacerbates sodium wasting in very preterm neonates: The premaldo study

International audienceContext: The neonatal period, notably in preterm infants, is characterized by high sodium wasting, implying that aldosterone, the main hormone regulating sodium reabsorption, is unable to maintain sodium homeostasis. Objective: This study sought to assess aldosterone secretion and action in neonates according to gestational age (GA). DesignandSetting: Thiswasamulticenter prospective study(NCT01176162)conductedbetween2011and 2014 at five neonatology departments in France. Infants were followed during their first 3 months. Participants: The 155 newborns included were classified into three groups: Group 1 (n = 46 patients), <33 gestational weeks (GW); Group 2 (n = 67 patients), 33-36 GW; and Group 3 (n = 42 patients), ≥37 GW. Main Outcome Measures: Plasma aldosterone was measured in umbilical cord blood. Urinary aldosterone (UAldo)wasassessed at day 0, day 3,month1,andmonth3 postnatal.ThecorrelationbetweenUAldoand the urinary Na/K ratio was determined as an index of renal aldosterone sensitivity. Results: UAldo significantly increased with GA: from 8.8 ± 7.5 μg/mmol of creatinine (Group 1) to 21.1 ± 21.0 (Group 3) in correlation with plasma aldosterone levels in all groups (P < .001), demonstrating its reliability. The aldosterone/renin ratio significantly increased with GA, suggesting an aldosterone secretion defect in preterm infants. UAldo and urinary Na/K were correlated in very preterm but not in term neonates, consistent with very preterm neonates being renal-aldosterone sensitive and term neonates being aldosterone resistant. Conclusions: Very preterm infants have a previously unrecognized defective aldosterone secretion but conserved renal aldosterone sensitivity in the neonatal period, which modifies the current view of sodium balance in these infants and suggests alternative management approaches. Copyrigh

Increased susceptibility to liver fibrosis with age is correlated with an altered inflammatory response.

International audienceIt has been suggested that increasing age is correlated with an acceleration of the progression of liver fibrosis induced by various agents, such as hepatitis C virus or chronic alcohol consumption. However, the cellular and molecular changes underlying this predisposition are not entirely understood. In the context of an aging population, it becomes challenging to decipher the mechanisms responsible for this higher susceptibility of older individuals to this acquired liver disorder. To address this issue, we induced liver fibrosis by carbon tetrachloride (CCl(4)) chronic administration to 8-week- and 15-month-old mice. We confirmed that susceptibility to fibrosis development increased with age and showed that aging did not affect fibrosis resolution capacity. We then focused on the impairment of hepatocyte proliferation, oxidative stress, and inflammation as potential mechanisms accelerating the development of fibrosis in the elderly. We detected no inhibition of hepatocyte proliferation after CCl(4) injury in 15-month-old mice, whereas it was inhibited after a partial hepatectomy. Finally, we observed that, in a context in which liver oxidative stress was not differentially increased in both experimental groups, there was a higher recruitment of inflammatory cells, including mostly macrophages and lymphocytes, oriented toward a T helper 2 (T(H)2) response in older mice. Our data show that in conditions of equivalent levels of oxidative stress and maintained hepatocyte proliferative capacity, an increased inflammatory reaction mainly composed of CD4(+) lymphocytes and macrophages expressing T(H)2 cytokines is the main factor involved in the higher susceptibility to fibrosis with increasing age