Etiology of community-acquired pneumonia in hospitalized children based on WHO clinical guidelines

Community-acquired pneumonia (CAP) is a major cause of death in developing countries and of morbidity in developed countries. The objective of the study was to define the causative agents among children hospitalized for CAP defined by WHO guidelines and to correlate etiology with clinical severity and surrogate markers. Investigations included an extensive etiological workup. A potential causative agent was detected in 86% of the 99 enrolled patients, with evidence of bacterial (53%), viral (67%), and mixed (33%) infections. Streptococcus pneumoniae was accounted for in 46% of CAP. Dehydration was the only clinical sign associated with bacterial pneumonia. CRP and PCT were significantly higher in bacterial infections. Increasing the number of diagnostic tests identifies potential causes of CAP in up to 86% of children, indicating a high prevalence of viruses and frequent co-infections. The high proportion of pneumococcal infections re-emphasizes the importance of pneumococcal immunizatio

Oxidative Stress and Mitochondrial Functions in the Intestinal Caco-2/15 Cell Line

Although mitochondrial dysfunction and oxidative stress are central mechanisms in various pathological conditions, they have not been extensively studied in the gastrointestinal tract, which is known to be constantly exposed to luminal oxidants from ingested foods. Key among these is the simultaneous consumption of iron salts and ascorbic acid, which can cause oxidative damage to biomolecules.The objective of the present work was to evaluate how iron-ascorbate (FE/ASC)-mediated lipid peroxidation affects mitochondrion functioning in Caco-2/15 cells. Our results show that treatment of Caco-2/15 cells with FE/ASC (0.2 mM/2 mM) (1) increased malondialdehyde levels assessed by HPLC; (2) reduced ATP production noted by luminescence assay; (3) provoked dysregulation of mitochondrial calcium homeostasis as evidenced by confocal fluorescence microscopy; (4) upregulated the protein expression of cytochrome C and apoptotic inducing factor, indicating exaggerated apoptosis; (5) affected mitochondrial respiratory chain complexes I, II, III and IV; (6) elicited mtDNA lesions as illustrated by the raised levels of 8-OHdG; (7) lowered DNA glycosylase, one of the first lines of defense against 8-OHdG mutagenicity; and (8) altered the gene expression and protein mass of mitochondrial transcription factors (mtTFA, mtTFB1, mtTFB2) without any effects on RNA Polymerase. The presence of the powerful antioxidant BHT (50 microM) prevented the occurrence of oxidative stress and most of the mitochondrial abnormalities.Collectively, our findings indicate that acute exposure of Caco-2/15 cells to FE/ASC-catalyzed peroxidation produces harmful effects on mitochondrial functions and DNA integrity, which are abrogated by the powerful exogenous BHT antioxidant. Functional derangements of mitochondria may have implications in oxidative stress-related disorders such as inflammatory bowel diseases

Mechanisms of metformin action on glucose transport and metabolism in human adipocytes

The mechanisms of metformin effects on glucose transport and metabolism were investigated in human adipocytes. Human preadipocytes obtained from surgical biopsies were differentiated in vitro into adipocytes and the effects of metformin on glucose uptake, glucose oxidation and the involved signaling pathways were analyzed. Metformin (1mM, 24h) increased glucose uptake 2.3±0.2-fold (p>0.001 vs. basal) in human adipocytes, without altering cell viability and oxygen consumption. Metformin did not alter GLUT-1 mRNA expression and protein content but increased GLUT-4 mRNA expression and cellular protein content, leading to increased GLUT-4 protein content in the plasma membrane. Neither basal nor insulin-induced phosphorylation of Akt at Ser-473 and AS160 (Akt substrate of 160kDa) at Thr-642 were enhanced by metformin. Suppression of metformin-induced AMP-activated protein kinase (AMPK) activity by AMPK?1 silencing, however, reduced metformin-associated GLUT-4 expression and stimulation of glucose uptake. In addition, metformin induced glucose oxidation. In conclusion, activation of AMPK?1 without impairment of cell respiration is crucial for metformin-mediated increase in GLUT-4 protein content and glucose uptake in human adipocytes

When fever, paracetamol? Theory and practice in a paediatric outpatient clinic

OBJECTIVE: To determine how medical and nursing staff treat feverish children and compare the findings with their theoretical knowledge, evaluating how they might contribute to fever phobia in parents.Setting: Paediatric Emergency Department. METHOD: In the first step, we analysed prospectively the files of all children having consulted the Paediatric Emergency Department with a history of fever or of body temperature above 38 degrees C during a 2-week period. The second step consisted of evaluating knowledge and perception of fever of doctors and nurses using a questionnaire. MAIN OUTCOME MEASURES: Prospective study: final diagnosis (viral, non- invasive bacterial disorders, invasive bacterial disorders), site of measurement and average temperature. Evaluation of theoretical knowledge: definition of fever, site of measurement, evaluation of the child's clinical state, antipyretic drug choice. RESULTS: A total of 114 children under 5 years of age were enrolled and 24 caregivers (12 doctors, 12 nurses, 90 of the staff) responded to the questionnaire. The results showed good consistency in theoretical knowledge, but an excessive fear about cerebral damage was also shown by doctors. This belief likely contributes to the transmission of fever phobia to parents. In contrast, analysis of children management showed that fever was often under-treated, especially by nurses and even more so by parents. Paracetamol remained the first-line antipyretic drug yet was often administered in insufficient doses. Non-steroidal anti-inflammatory drugs were seldom used, except by parents (16 of all the children). Contrary to literature, the favourite route of administration was the rectal one. Physical methods like sponging were largely used by nurses, despite the uncertainties in their real effectiveness and their known side-effects. CONCLUSION: Our study showed that the management of feverish children was globally correct in the Paediatric Emergency Department, but several improvement measures have been taken (e.g. tables of normal and abnormal ranges of temperature, recommended temperature measurement techniques, dosage regimen of antipyretic drugs, guidelines to parents), justifying the implementation of a pharmaceutical follow-up

Introducing the CTA concept

The Cherenkov Telescope Array (CTA) is a new observatory for very high-energy (VHE) gamma rays. CTA has ambitions science goals, for which it is necessary to achieve full-sky coverage, to improve the sensitivity by about an order of magnitude, to span about four decades of energy, from a few tens of GeV to above 100 TeV with enhanced angular and energy resolutions over existing VHE gamma-ray observatories. An international collaboration has formed with more than 1000 members from 27 countries in Europe, Asia, Africa and North and South America. In 2010 the CTA Consortium completed a Design Study and started a three-year Preparatory Phase which leads to production readiness of CTA in 2014. In this paper we introduce the science goals and the concept of CTA, and provide an overview of the project. © 2013 Elsevier B.V. All rights reserved