Prevalence of Nosocomial Infections in Swiss Children's Hospitals

Abstract Objective: To acquire data on pediatric nosocomial infections (NIs), which are associated with substantial morbidity and mortality and for which data are scarce. Design: Prevalence survey and evaluation of a new comorbidity index. Setting: Seven Swiss pediatric hospitals. Patients: Those hospitalized for at least 24 hours in a medical, surgical, intensive care, or intermediate care ward. Results: Thirty-five NIs were observed among 520 patients (6.7%; range per hospital, 1.4% to 11.8%). Bacteremia was most frequent (2.5 per 100 patients), followed by urinary tract infection (1.3 per 100 patients) and surgical-site infection (1.1 per 100 patients; 3.2 per 100 patients undergoing surgery). The median duration until the onset of infection was 19 days. Independent risk factors for NI were age between 1 and 12 months, a comorbidity score of 2 or greater, and a urinary catheter. Among surgical patients, an American Society of Anesthesiologists (ASA) score of 2 or greater was associated with any type of NI (P = .03). Enterobacteriaceae were the most frequent cause of NI, followed by coagulase-negative staphylococci; viruses were rarely the cause. Conclusions: This national prevalence survey yielded valuable information about the rate and risk factors of pediatric NI. A new comorbidity score showed promising performance. ASA score may be a predictor of NI. The season in which a prevalence survey is conducted must be considered, as this determines whether seasonal viral infections are observed. Periodic prevalence surveys are a simple and cost-effective method for assessing NI and comparing rates among pediatric hospital

Prevalence of nosocomial infections in Swiss children's hospitals

OBJECTIVE: To acquire data on pediatric nosocomial infections (NIs), which are associated with substantial morbidity and mortality and for which data are scarce. DESIGN: Prevalence survey and evaluation of a new comorbidity index. SETTING: Seven Swiss pediatric hospitals. PATIENTS: Those hospitalized for at least 24 hours in a medical, surgical, intensive care, or intermediate care ward. RESULTS: Thirty-five NIs were observed among 520 patients (6.7%; range per hospital, 1.4% to 11.8%). Bacteremia was most frequent (2.5 per 100 patients), followed by urinary tract infection (1.3 per 100 patients) and surgical-site infection (1.1 per 100 patients; 3.2 per 100 patients undergoing surgery). The median duration until the onset of infection was 19 days. Independent risk factors for NI were age between 1 and 12 months, a comorbidity score of 2 or greater, and a urinary catheter. Among surgical patients, an American Society of Anesthesiologists (ASA) score of 2 or greater was associated with any type of NI (P = .03). Enterobacteriaceae were the most frequent cause of NI, followed by coagulase-negative staphylococci; viruses were rarely the cause. CONCLUSIONS: This national prevalence survey yielded valuable information about the rate and risk factors of pediatric NI. A new comorbidity score showed promising performance. ASA score may be a predictor of NI. The season in which a prevalence survey is conducted must be considered, as this determines whether seasonal viral infections are observed. Periodic prevalence surveys are a simple and cost-effective method for assessing NI and comparing rates among pediatric hospitals

Impact of disease mutations on the desmin filament assembly process

It has been documented that mutations in the human desmin gene lead to a severe type of myofibrillar myopathy, termed more specifically desminopathy, which affects cardiac and skeletal as well as smooth muscle. We showed recently that 14 recombinant versions of these disease-causing desmin variants, all involving single amino acid substitutions in the a-helical rod domain, interfere with in vitro filament formation at distinct stages of the assembly process. We now provide mechanistic details of how these mutations affect the filament assembly process by employing anal. ultracentrifugation, time-lapse electron microscopy of neg. stained and glycerol-sprayed/low-angle rotary metal-shadowed samples, quant. scanning TEM, and viscometric studies. In particular, the sol. assembly intermediates of two of the mutated proteins exhibit unusually high s-values, compatible with octamers and other higher-order complexes. Moreover, several of the six filament-forming mutant variants deviated considerably from wild-type desmin with respect to their filament diams. and mass-per-length values. In the heteropolymeric situation with wild-type desmin, four of the mutant variants caused a pronounced "hyper-assembly", when assayed by viscometry. This indicates that the various mutations may cause abortion of filament formation by the mutant protein at distinct stages, and that some of them interfere severely with the assembly of wild-type desmin. Taken together, our findings provide novel insights into the basic intermediate filament assembly mechanisms and offer clues as to how amino acid changes within the desmin rod domain may interfere with the normal structural organization of the muscle cytoskeleton, eventually leading to desminopathy. [on SciFinder (R)

Ca2+-Dependent Interaction of S100A1 with F1-ATPase Leads to an Increased ATP Content in Cardiomyocytes▿

S100A1, a Ca2+-sensing protein of the EF-hand family that is expressed predominantly in cardiac muscle, plays a pivotal role in cardiac contractility in vitro and in vivo. It has recently been demonstrated that by restoring Ca2+ homeostasis, S100A1 was able to rescue contractile dysfunction in failing rat hearts. Myocardial contractility is regulated not only by Ca2+ homeostasis but also by energy metabolism, in particular the production of ATP. Here, we report a novel interaction of S100A1 with mitochondrial F1-ATPase, which affects F1-ATPase activity and cellular ATP production. In particular, cardiomyocytes that overexpress S100A1 exhibited a higher ATP content than control cells, whereas knockdown of S100A1 expression decreased ATP levels. In pull-down experiments, we identified the α- and β-chain of F1-ATPase to interact with S100A1 in a Ca2+-dependent manner. The interaction was confirmed by colocalization studies of S100A1 and F1-ATPase and the analysis of the S100A1-F1-ATPase complex by gel filtration chromatography. The functional impact of this association is highlighted by an S100A1-mediated increase of F1-ATPase activity. Consistently, ATP synthase activity is reduced in cardiomyocytes from S100A1 knockout mice. Our data indicate that S100A1 might play a key role in cardiac energy metabolism

Ca 2ϩ -Dependent Interaction of S100A1 with F 1 -ATPase Leads to an Increased ATP Content in Cardiomyocytes

S100A1, a Ca 2؉ -sensing protein of the EF-hand family that is expressed predominantly in cardiac muscle, plays a pivotal role in cardiac contractility in vitro and in vivo. It has recently been demonstrated that by restoring Ca 2؉ homeostasis, S100A1 was able to rescue contractile dysfunction in failing rat hearts. Myocardial contractility is regulated not only by Ca 2؉ homeostasis but also by energy metabolism, in particular the production of ATP. Here, we report a novel interaction of S100A1 with mitochondrial F 1 -ATPase, which affects F 1 -ATPase activity and cellular ATP production. In particular, cardiomyocytes that overexpress S100A1 exhibited a higher ATP content than control cells, whereas knockdown of S100A1 expression decreased ATP levels. In pull-down experiments, we identified the ␣-and ␤-chain of F 1 -ATPase to interact with S100A1 in a Ca 2؉ -dependent manner. The interaction was confirmed by colocalization studies of S100A1 and F 1 -ATPase and the analysis of the S100A1-F 1 -ATPase complex by gel filtration chromatography. The functional impact of this association is highlighted by an S100A1-mediated increase of F 1 -ATPase activity. Consistently, ATP synthase activity is reduced in cardiomyocytes from S100A1 knockout mice. Our data indicate that S100A1 might play a key role in cardiac energy metabolism. S100 proteins are a family of soluble, EF-hand Ca 2ϩ -binding proteins which exhibit a remarkable cell-and tissue-specific expression pattern. They are involved in numerous intracellular activities, such as cell proliferation and differentiation, or the dynamics of cytoskeletal constituents (reviewed in references 4, 9, and 30). The most abundant S100 protein in the heart is S100A1 (12; reviewed in reference 4). It has been recognized recently as a positive inotropic intracellular regulator of cardiac as well as skeletal muscle Ca 2ϩ homeostasis and contractility In addition to Ca 2ϩ homeostasis, myocardial workload depends on cardiac metabolism. As the energy demand changes, the flux through the mitochondrial ATP synthase (F 1 F oATPase), which is responsible for the bulk of ATP synthesis in the myocardium, must change so that ATP synthesis matches ATP consumption (reviewed in references 6 and 10). To sustain cardiac function in all possible situations, there has to be a strict correlation between energy production, energy transfer, and energy utilization (reviewed in reference 29). In this regard, Ca 2ϩ has emerged as a major factor for adapting mitochondrial ATP production to the constantly varying energy demand of the cell. Consistently, several studies provided evidence that F 1 F o -ATPase-dependent ATP synthesis correlates with Ca 2ϩ levels in heart cells (reviewed in reference 1). Furthermore, metabolic pathway abnormalities that result in an imbalance of several metabolic reactions, for example, a decreased phosphocreatine/ATP ratio, indicative of an increase in ADP, an alteration of oxidative phosphorylation, and a decreased ATP/ADP ratio, lead to abnormal contraction and relaxation and eventually result in the failing of the heart. Thus, it is conceivable that energy starvation may contribute to heart failure (reviewed in reference 11). Because S100A1 is able to restore a reduced phosphocreatine/ATP ratio and Ca 2ϩ homeostasis in failing cardiomyocytes (19), we examined whether S100A1 has an influence on cardiac energy homeostasis in neonatal rat ventricular cardiomyocytes (NVCMs). Here, we demonstrate a Ca 2ϩ -dependent interaction of S100A1 with the ␣-and ␤-chain of the F 1 -ATPase in NVCMs and isolated mitochondria. Moreover, this interaction is consolidated by colocalization in immunofluorescence and immunoelectron microscopy studies and the isolation of an S100A1-F 1 -ATPase complex by gel filtration chromatography. Furthermore, the physiological significance of S100A1 in energy metabolism is validated through the effects of S100A1 overexpression and knock-* Corresponding author. Mailing address: Maurice E. Mueller In

Distinct subcellular location of the Ca2+-binding protein S100A1 differentially modulates Ca2+-cycling in ventricular rat cardiomyocytes

Calcium is a key regulator of cardiac function and is modulated through the Ca2+-sensor protein S100A1. S100 proteins are considered to exert both intracellular and extracellular functions on their target cells. Here we report the impact of an increased intracellular S100A1 protein level on Ca2+-homeostasis in neonatal ventricular cardiomyocytes in vitro. Specifically, we compare the effects of exogenously added recombinant S100A1 to those resulting from the overexpression of a transduced S100A1 gene. Extracellularly added S100A1 enhanced the Ca2+-transient amplitude in neonatal ventricular cardiomyocytes (NVCMs) through a marked decrease in intracellular diastolic Ca2+-concentrations ([Ca2+]i). The decrease in [Ca2+]i was independent of sarcoplasmic reticulum Ca2+-ATPase (SERCA2a) activity and was probably the result of an increased sarcolemmal Ca2+-extrusion through the sodium-calcium exchanger (NCX). At the same time the Ca2+-content of the sarcoplasmic reticulum (SR) decreased. These effects were dependent on the uptake of extracellularly added S100A1 protein and its subsequent routing to the endosomal compartment. Phospholipase C and protein kinase C, which are tightly associated with this subcellular compartment, were found to be activated by endocytosed S100A1. By contrast, adenoviral-mediated intracellular S100A1 overexpression enhanced the Ca2+-transient amplitude in NVCMs mainly through an increase in systolic [Ca2+]i. The increased Ca2+-load in the SR was based on an enhanced SERCA2a activity while NCX function was unaltered. Overexpressed S100A1 colocalized with SERCA2a and other Ca2+-regulatory proteins at the SR, whereas recombinant S100A1 protein that had been endocytosed did not colocalize with SR proteins. This study provides the first evidence that intracellular S100A1, depending on its subcellular location, modulates cardiac Ca2+-turnover via different Ca2+-regulatory proteins