[European society of cardiology guidelines for the management of infective endocarditis (partim 1)]. / Recommandations européennes sur la prise en charge de l'endocardite infectieuse (partim 1).

Until recently, the recommendations of infective endocarditis were based on expert opinions, due to its low incidence and the absence of controlled trials. The update in 2015 of the new guidelines of the European Society of Cardiology (compared with 2009) relates to the publication of a randomised study on the surgical treatment, the innovations in imaging procedures (especially functional imaging in nuclear medicine) and the new concept of «Team Endocarditis¼ (multidisciplinary approach). Their aim is to remind the limitations of antibiotic prophylaxis and to insist on hospital hygiene measures. Future challenges will be to obtain a better understanding of the mechanisms associated with the contamination of the valve and to optimize the adaptation of the current epidemiological prophylaxis. In this first part, we will describe the preventive and diagnostic approaches of infective endocarditis.

Jusqu'à ce jour, les recommandations concernant le traitement de l'endocardite infectieuse étaient essentiellement basées sur l'opinion d'experts, à cause de sa faible incidence et de l'absence d'essais contrôlés. La mise à jour, en 2015, des recommandations de la Société Européenne de Cardiologie de 2009, est justifiée par la publication d'une première étude randomisée sur le traitement chirurgical, par les innovations concernant les procédures d'imagerie (particulièrement l'imagerie fonctionnelle en médecine nucléaire) et par le nouveau concept d'«Endocarditis Team¼ (approche multidisciplinaire). Ces directives européennes ont le mérite de rappeler les limitations de l'antibioprophylaxie et d'insister sur les mesures préventives à prodiguer. Les défis futurs seront de mieux comprendre les mécanismes associés à la contamination de l'endocarde valvulaire et de mieux adapter la prophylaxie à l'évolution épidémiologique. Dans cette première partie, nous décrivons la prophylaxie et les moyens diagnostiques de l'endocardite infectieuse.

[Modulation of tissue exposure to cortisol, new perspective for reducing the metabolic risk associated with obesity]. / Moduler l'exposition tissulaire au cortisol, nouvelle perspective pour réduire le risque métabolique associé a l'obésité.

Pharmaceutical research is looking for new alternatives to manage the metabolic disorders associated with obesity. In this context, 11beta hydroxysteroid dehydrogenase type 1 (11HSD1) represents an interesting target. Indeed, this enzyme activates the transformation of inactive cortisone into active cortisol in various tissues. Therefore, it may be responsible for a local hypercortisolism, in adipose tissue and/or liver, which may be implicated in the pathogenesis of abdominal obesity, metabolic syndrome and type 2 diabetes. Thus, the inhibition of 11HSD1 may represent a potential pharmacological target and an innovative therapeutic goal. Several studies in both animals and humans led to the development of specific 11HSD1 inhibitors, with promising preliminary results. Indeed, a reduction in insulin resistance and significant improvements in carbohydrate and lipid profiles have been reported. The present article describes the rationale that led to the development of specific 11HSD1 inhibitors and briefly reports the first results obtained with these molecules, which may become a new class of antidiabetic agents in the future.

A test of the nature of cosmic acceleration using galaxy redshift distortions.

Observations of distant supernovae indicate that the Universe is now in a phase of accelerated expansion the physical cause of which is a mystery. Formally, this requires the inclusion of a term acting as a negative pressure in the equations of cosmic expansion, accounting for about 75 per cent of the total energy density in the Universe. The simplest option for this 'dark energy' corresponds to a 'cosmological constant', perhaps related to the quantum vacuum energy. Physically viable alternatives invoke either the presence of a scalar field with an evolving equation of state, or extensions of general relativity involving higher-order curvature terms or extra dimensions. Although they produce similar expansion rates, different models predict measurable differences in the growth rate of large-scale structure with cosmic time. A fingerprint of this growth is provided by coherent galaxy motions, which introduce a radial anisotropy in the clustering pattern reconstructed by galaxy redshift surveys. Here we report a measurement of this effect at a redshift of 0.8. Using a new survey of more than 10,000 faint galaxies, we measure the anisotropy parameter beta = 0.70 +/- 0.26, which corresponds to a growth rate of structure at that time of f = 0.91 +/- 0.36. This is consistent with the standard cosmological-constant model with low matter density and flat geometry, although the error bars are still too large to distinguish among alternative origins for the accelerated expansion. The correct origin could be determined with a further factor-of-ten increase in the sampled volume at similar redshift.

S100A2 gene is a direct transcriptional target of p53 homologues during keratinocyte differentiation.

The p53 paralogues p73, p63 and their respective truncated isoforms have been shown to be critical regulators of developmental and differentiation processes. Indeed, both p73- and p63-deficient mice exhibit severe developmental defects. Here, we show that S100A2 gene, whose transcript and protein are induced during keratinocyte differentiation of HaCaT cells, is a direct transcriptional target of p73beta and DeltaNp63alpha and is required for proper keratinocyte differentiation. Transactivation assays reveal that p73beta and DeltaNp63alpha exert opposite transcriptional effects on S100A2 gene. While DeltaNp63alpha is found in vivo onto S100A2 regulatory regions predominantly in proliferating cells, p73beta is recruited in differentiating cells. Silencing of p73 impairs the induction of S100A2 during the differentiation of HaCaT cells. Moreover, silencing of p73 or S100A2 impairs the proper expression of keratinocyte differentiation markers. Of note, p53 family members do not trigger S100A2 gene expression in response to apoptotic doses of cisplatin and doxorubicin.

A large population of galaxies 9 to 12 billion years back in the history of the Universe.

To understand the evolution of galaxies, we need to know as accurately as possible how many galaxies were present in the Universe at different epochs. Galaxies in the young Universe have hitherto mainly been identified using their expected optical colours, but this leaves open the possibility that a significant population remains undetected because their colours are the result of a complex mix of stars, gas, dust or active galactic nuclei. Here we report the results of a flux-limited I-band survey of galaxies at look-back times of 9 to 12 billion years. We find 970 galaxies with spectroscopic redshifts between 1.4 and 5. This population is 1.6 to 6.2 times larger than previous estimates, with the difference increasing towards brighter magnitudes. Strong ultraviolet continua (in the rest frame of the galaxies) indicate vigorous star formation rates of more than 10-100 solar masses per year. As a consequence, the cosmic star formation rate representing the volume-averaged production of stars is higher than previously measured at redshifts of 3 to 4.

Simultaneous peripubertal onset of multireactive autoimmune diseases with an unusual long-lasting remission of type 1 diabetes mellitus.

Although it is well known that patients with type 1 diabetes mellitus are susceptible to other autoimmune diseases, the simultaneous occurrence of clustered distinct autoimmune diseases is uncommon. We report a 16-year-old girl, previously diagnosed as having coeliac disease and IgA deficiency, who at 13 years of age developed a clustering of distinct autoimmune diseases, including type 1 diabetes mellitus, rheumatoid arthritis (RA) and euthyroid autoimmune thyroiditis, eventually resulting in a simultaneous long-term remission. The clinical picture was associated with a functional immunodeficiency characterized by a defect in proliferative responses to T cell predominant mitogens and a normal response to the B cell predominant mitogen. In addition, the T cell activation markers HLA-DR, IL-2 receptor and transferrin receptor) were not upregulated. The clinical course of this immunodeficiency paralleled the outcome of the autoimmune diseases. After the abrupt onset, spontaneous clinical remission of both diabetes mellitus and RA was observed. Insulin was first reduced in dose and then discontinued completely at 15 months, in the presence of normal C peptide secretion and normal metabolic control (HbA1c 5.8%). Anti-glutamate decarboxylase (GAD65) and anti-IA-2 antibodies remained persistently high. During the remission phase a normalization of the functional immune defect was observed. The gradual resolution of the multisystemic diseases as well as the normalization of immune function in our patient is unusual. This case may be of considerable value in furthering our knowledge of the immunological mechanisms implicated in these rare multireactive syndromes.