[Optimization in the detection of bacteremia: Integrated use of FilmArray (BCID2) and MALDI-TOF]. / Optimización en la detección de bacteriemias. Uso integrado de FilmArray (BCID2) y MALDI-TOF.

The usefulness of the combined use of MALDI-TOF MS from a subculture with 3-5h of incubation and the BCID2 panel (FilmArray) for the identification of microorganisms from positive blood cultures and its importance in the adjustment of antimicrobial therapy was analyzed. Overall identification with BCID2 was 90.4% (142/157) and with Maldi-TOF MS 83.4% (131/157) (p=0.0858); in 23 polymicrobial episodes (47 strains), the BCID2 panel identified 45 (95.7%) and MALDI-TOF MS 24 (51.1%) (p<0.0000). BCID2 detected the presence of the resistance genes mecA/C (n=16), blaKPC (n=8); blaCTX-M (n=17), blaNDM (n=8), blaOXA-48 (n=1), and vanA/B (n=2). The median time to report a result was 2.0h for BCID2 and 4.0h for MALDI-TOF MS (p<0.0000). Of 124 episodes analyzed, the rapid result of BCID2 led to 82.3% (102/124) therapeutic changes.

Variants in the Oxidoreductase PYROXD1 Cause Early-Onset Myopathy with Internalized Nuclei and Myofibrillar Disorganization.

This study establishes PYROXD1 variants as a cause of early-onset myopathy and uses biospecimens and cell lines, yeast, and zebrafish models to elucidate the fundamental role of PYROXD1 in skeletal muscle. Exome sequencing identified recessive variants in PYROXD1 in nine probands from five families. Affected individuals presented in infancy or childhood with slowly progressive proximal and distal weakness, facial weakness, nasal speech, swallowing difficulties, and normal to moderately elevated creatine kinase. Distinctive histopathology showed abundant internalized nuclei, myofibrillar disorganization, desmin-positive inclusions, and thickened Z-bands. PYROXD1 is a nuclear-cytoplasmic pyridine nucleotide-disulphide reductase (PNDR). PNDRs are flavoproteins (FAD-binding) and catalyze pyridine-nucleotide-dependent (NAD/NADH) reduction of thiol residues in other proteins. Complementation experiments in yeast lacking glutathione reductase glr1 show that human PYROXD1 has reductase activity that is strongly impaired by the disease-associated missense mutations. Immunolocalization studies in human muscle and zebrafish myofibers demonstrate that PYROXD1 localizes to the nucleus and to striated sarcomeric compartments. Zebrafish with ryroxD1 knock-down recapitulate features of PYROXD1 myopathy with sarcomeric disorganization, myofibrillar aggregates, and marked swimming defect. We characterize variants in the oxidoreductase PYROXD1 as a cause of early-onset myopathy with distinctive histopathology and introduce altered redox regulation as a primary cause of congenital muscle disease.

[Phosphoinositides: lipidic essential actors in the intracellular traffic]. / Les phosphoinositides, des lipides acteurs essentiels du trafic intracellulaire.

Phosphoinositides (PPIn) are lipids involved in the vesicular transport of proteins between the different intracellular compartments. They act by recruiting and/or activating effector proteins and are thus involved in crucial cellular functions including vesicle budding, fusion and dynamics of membranes and regulation of the cytoskeleton. Although they are present in low concentrations in membranes, their activity is essential for cell survival and needs to be tightly controlled. Therefore, phosphatases and kinases specific of the various cellular membranes can phosphorylate/dephosphorylate their inositol ring on the positions D3, D4 and/or D5. The differential phosphorylation determines the intracellular localisation and the activity of the PPIn. Indeed, non-phosphorylated phosphatidylinositol (PtdIns) is the basic component of the PPIn and can be found in all eukaryotic cells at the cytoplasmic face of the ER, the Golgi, mitochondria and microsomes. It can get phosphorylated on position D4 to obtain PtdIns4P, a PPIn enriched in the Golgi compartment and involved in the maintenance of this organelle as well as anterograde and retrograde transport to and from the Golgi. PtdIns phosphorylation on position D3 results in PtdIns3P that is required for endosomal transport and multivesicular body (MVB) formation and sorting. These monophosphorylated PtdIns can be further phosphorylated to produce bisphophorylated PtdIns. Thus, PtdIns(4,5)P2, mainly produced by PtdIns4P phosphorylation, is enriched in the plasma membrane and involved in the regulation of actin cytoskeleton and endocytosis. PtdIns(3,5)P2, mainly produced by PtdIns3P phosphorylation, is enriched in late endosomes, MVBs and the lysosome/vacuole and plays a role in endosome to vacuole transport. PtdIns(3,4)P2 is absent in yeast, cells and mainly produced by PtdIns4P phosphorylation in human cells; PtdIns(3,4)P2 is localised in the plasma membrane and plays an important role as a second messenger by recruiting specific protein kinases (Akt and PDK1). Finally the triple phosphorylated PPIn, PtdIns(3,4,5)P3 also absent in yeast, is produced by the phosphorylation of PtdIns(3,4)P2 and localized at the plasma membrane of human cells where it binds proteins via their PH domain. Interaction partners include members of the Arf (ADP-ribosylation factors) family, PDK1 (Phosphoinositide Dependent Kinase 1) and Akt. Therefore this last PPIn is essential for the control of cell proliferation and its deregulation leads to the development of numerous cancers. In conclusion, the regulation of PPIn phosphorylation/dephosphorylation is complex and needs to be very precisely regulated. Indeed phosphatases and kinases allow the maintenance of the equilibrium between the different forms. PPIn play a crucial role in numerous cellular functions and a loss in their synthesis or regulation results in severe genetic diseases.

[Metastatic infections in children with Staphylococcus aureus bacteremia]. / Localización metastásica en niños con bacteriemia por Staphylococcus aureus.

Staphylococcus aureus is one of the most common infectious agents in children. It causes a broad spectrum of infections ranging from trivial to severe life-threatening presentations. The possibility of complications in case of Staphylococcus aureus bacteremia (SAB) appears to be high, being described in up to 43% of cases in adult patients. However, metastatic infections seems to be less frequent in pediatric patients. There is no agreement on when or to whom complementary tests should be requested to rule them out. The aim of this study is to describe the frequency and characteristics of secondary impacts of SAB identified at "Hospital Gutierrez" in a period of two years, and assess potential risk factors for their occurrence. Metastatic infection rate was 15.8%. The main risk factor was the persistence of positive blood cultures more than 48 hours.

Eritema nodoso asociado con enfermedad periodontal: reporte de un caso / Nodosum erythema in association with periodontal disease: report of a case

El eritema nodoso (EN) es una reacción inflamatoria caracterizada por lesiones nodulares subcutáneas en superficies extensoras y más frecuentemente, en las extremidades inferiores. El EN se asocia con una variedad de padecimientos, en su mayoría infecciosos, inducidos por fármacos o por problemas neoplásicos. Este es un caso en donde el EN crónico está asociado a enfermedad periodontal recurrente. En cuanto la enfermedad periodontal se resolvió, el EN remitió