121 research outputs found
F-02: Antibiothérapies anti-SARM dans le traitement probabiliste des bactériémies à Staphylococcus aureus au CHU d'Angers
Introduction â objectifs
La résistance à la méticilline du Staphylococcus aureus (SA) ne cesse de diminuer en France. Nous avons évalué la prescription des antibiothérapies probabilistes dans les bactériémies à SA et leur impact clinique.
Matériels et méthodes
Il sâagit dâune Ă©tude rĂ©trospective incluant les bactĂ©riĂ©mies Ă Staphylococcus aureus sur le CHU dâAngers entre novembre 2012 et septembre 2013 avec recueil de lâantibiothĂ©rapie prescrite au rendu « cocci gram (CG)+ », Ă J5, hospitalisation depuis plus de 5 jours ou dans les six derniers mois, signes de gravitĂ© clinique, mortalitĂ© Ă J5.
RĂ©sultats
Nous avons inclus 146 Ă©pisodes de bactĂ©riĂ©mies. A lâannonce de CG+, 10 patients Ă©taient dĂ©cĂ©dĂ©s, 38,2 % ont reçu un anti-SARM (n = 52), 54,4 % un anti-SASM (n = 74), 7,4 % aucun antibiotique (n = 10). Parmi les bactĂ©riĂ©mies Ă SARM (n = 23), 60,9 % (n = 14) ont reçu une antibiothĂ©rapie initiale Ă visĂ©e SARM contre 36,3 % (n = 41) pour les bactĂ©riĂ©mies Ă SASM (n = 113) (OR = 2,71, p = 0,03). Cette adaptation semble influencĂ©e par une hospitalisation rĂ©cente (OR = 1,82 ; p = 0,33) et la prĂ©sence de signes de gravitĂ© (OR = 1,87, p = 0,23). Dans 21,4 % (n = 6) des bactĂ©riĂ©mies Ă SASM, lâantibiothĂ©rapie anti-SARM nâa pas Ă©tĂ© dĂ©secaladĂ©e. La mortalitĂ© Ă J5 est 13 %. Lâabsence dâantibiothĂ©rapie dans les 24 premiĂšres heures (OR = 2,97 ; p = 0,046) et une prescription de C3G (OR = 5,2, p = 0,05) en monothĂ©rapie augmentent le risque de dĂ©cĂšs Ă J5.
Conclusion
LâantibiothĂ©rapie initale semble adaptĂ©e Ă lâhistoire et la prĂ©sentation des patients. Lâinitiation sans dĂ©lai, la visĂ©e staphylococcique et la dĂ©sescalade sont les Ă©lĂ©ments importants du traitement
Calmodulin acts as a state-dependent switch to control a cardiac potassium channel opening
Calmodulin (CaM) and phosphatidylinositol 4,5-bisphosphate (PI
Canine CNGA3 Gene Mutations Provide Novel Insights Into Human Achromatopsia-Associated Channelopathies and Treatment
Cyclic nucleotide-gated (CNG) ion channels are key mediators underlying signal transduction in retinal and olfactory receptors. Genetic defects in CNGA3 and CNGB3, encoding two structurally related subunits of cone CNG channels, lead to achromatopsia (ACHM). ACHM is a congenital, autosomal recessive retinal disorder that manifests by cone photoreceptor dysfunction, severely reduced visual acuity, impaired or complete color blindness and photophobia. Here, we report the first canine models for CNGA3-associated channelopathy caused by R424W or V644del mutations in the canine CNGA3 ortholog that accurately mimic the clinical and molecular features of human CNGA3-associated ACHM. These two spontaneous mutations exposed CNGA3 residues essential for the preservation of channel function and biogenesis. The CNGA3-R424W results in complete loss of cone function in vivoand channel activity confirmed by in vitro electrophysiology. Structural modeling and molecular dynamics (MD) simulations revealed R424-E306 salt bridge formation and its disruption with the R424W mutant. Reversal of charges in a CNGA3-R424E-E306R double mutant channel rescued cGMP-activated currents uncovering new insights into channel gating. The CNGA3-V644del affects the C-terminal leucine zipper (CLZ) domain destabilizing intersubunit interactions of the coiled-coil complex in the MD simulations; the in vitro experiments showed incompetent trimeric CNGA3 subunit assembly consistent with abnormal biogenesis of in vivochannels. These newly characterized large animal models not only provide a valuable system for studying cone-specific CNG channel function in health and disease, but also represent prime candidates for proof-of-concept studies of CNGA3 gene replacement therapy for ACHM patients
Calmodulin C-term domain binding the voltage-gated sodium channel Na<sub>V</sub>1.2.
<p>a) Ca<sup>2+</sup>-free state (apo) and b) Ca<sup>2+</sup>-bound state
(holo). The structures have PDB accession numbers a) 2KXW and b) 4JPZ. The target protein backbone is shown as a violet ribbon and its side chains are depicted as violet sticks. Hydrophobic residues are visualized in a white mesh. Key hydrophobic residues found in this paperâs analysis are highlighted in different colors. The residues are shown in <a href="http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1006072#pcbi.1006072.s001" target="_blank">S1</a> and <a href="http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1006072#pcbi.1006072.s003" target="_blank">S3</a> Figs.</p
Residue definition of the calmodulin alpha helices.
<p>Residue definition of the calmodulin alpha helices.</p
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