Plasma lipid profiles discriminate bacterial from viral infection in febrile children

Fever is the most common reason that children present to Emergency Departments. Clinical signs and symptoms suggestive of bacterial infection are often non-specific, and there is no definitive test for the accurate diagnosis of infection. The 'omics' approaches to identifying biomarkers from the host-response to bacterial infection are promising. In this study, lipidomic analysis was carried out with plasma samples obtained from febrile children with confirmed bacterial infection (n = 20) and confirmed viral infection (n = 20). We show for the first time that bacterial and viral infection produces distinct profile in the host lipidome. Some species of glycerophosphoinositol, sphingomyelin, lysophosphatidylcholine and cholesterol sulfate were higher in the confirmed virus infected group, while some species of fatty acids, glycerophosphocholine, glycerophosphoserine, lactosylceramide and bilirubin were lower in the confirmed virus infected group when compared with confirmed bacterial infected group. A combination of three lipids achieved an area under the receiver operating characteristic (ROC) curve of 0.911 (95% CI 0.81 to 0.98). This pilot study demonstrates the potential of metabolic biomarkers to assist clinicians in distinguishing bacterial from viral infection in febrile children, to facilitate effective clinical management and to the limit inappropriate use of antibiotics

Plasma lipid profiles discriminate bacterial from viral infection in febrile children

Fever is the most common reason that children present to Emergency Departments. Clinical signs and symptoms suggestive of bacterial infection ar

Neonatal hypoxia-ischaemia disrupts descending neural inputs to dorsal raphé nuclei

Neuronal losses have been shown to occur in the brainstem following a neonatal hypoxic-ischaemic (HI) insult. In particular serotonergic neurons, situated in the dorsal raphe nuclei, appear to be vulnerable to HI injury. Nonetheless the mechanisms contributing to losses of serotonergic neurons in the brainstem remain to be elucidated. One possible mechanism is that disruption of neural projections from damaged forebrain areas to dorsal raphe nuclei may play a role in the demise of serotonergic neurons. To test this, postnatal day 3 (P3) rat pups underwent unilateral common carotid artery ligation followed by hypoxia (6% O-2 for 30 min). On P38 a retrograde tracer, fluorescent-coupled choleratoxin b, was deposited in the dorsal raphe dorsal (DR dorsal) nucleus or the dorsal raphe ventral (DR ventral) nucleus. Compared to control animals, P3 HI animals had significant losses of retrogradely labelled neurons in the medial prefrontal cortex, preoptic area and lateral habenula after tracer deposit in the DR dorsal nucleus. On the other hand, after tracer deposit in the DR ventral nucleus, we found significant reductions in numbers of retrogradely labelled neurons in the hypothalamus, preoptic area and medial amygdala in P3 HI animals compared to controls. Since losses of descending inputs are associated with decreases in serotonergic neurons in the brainstem raphe nuclei, we propose that disruption of certain descending neural inputs from the forebrain to the DR dorsal and the DR ventral nuclei may contribute to losses of serotonergic neurons after P3 HI. It is important to delineate the phenotypes of different neuronal networks affected by neonatal HI, and the mechanisms underpinning this damage, so that interventions can be devised to target and protect axons from the harmful effects of neonatal HI. (C) 2013 IBRO. Published by Elsevier Ltd. All rights reserved

Ibuprofen inhibits neuroinflammation and attenuates white matter damage following hypoxia-ischemia in the immature rodent brain

Damage to major white matter tracts is a hallmark mark feature of hypoxic ischemic (HI) brain injury in the preterm neonate. There is, however, no therapeutic intervention to treat this injury. Neuroinflammation is thought to play a prominent role in the pathogenesis of the HI-induced white matter damage but identification of the key mediators that constitute the inflammatory response remain to be fully elucidated. Cyclooxygenase enzymes (COX-1 and COX-2) are candidate neuroinflammatory mediators that may contribute to the HI-induced demise of early oligodendrocyte progenitors and myelination. We investigated whether ibuprofen, a non-steroidal anti-inflammatory drug that inhibits COX enzymes, can attenuate neuroinflammation and associated white matter damage incurred in a rodent model of preterm HI. On postnatal day 3 (P3), HI was produced (right carotid artery ligation and 30 mm 6% O(2)). An initial dose of ibuprofen (100 mg,/kg, s.c.) was administered 2 h after HI followed by a maintenance dose (50 mg/kg, s.c.) every 24 h for 6 days. Post-HI ibuprofen treatment significantly attenuated the P3 HI-induced increases in COX-2 protein expression as well as interleukin-1beta (IL-1 beta) and tumour necrosis factor-alpha (TNF-alpha) levels in the brain. Ibuprofen treatment also prevented the HI-induced loss O4- and O1-positive oligodendrocyte progenitor cells and myelin basic protein (MBP)-positive myelin content one week after P3 HI. These findings suggest that a repeated, daily, ibuprofen treatment regimen administered after an HI insult may be a potential therapeutic intervention to prevent HI-induced damage to white matter progenitors and early myelination in the preterm neonate. (C) 2011 Elsevier B.V. All rights reserved

Stressor categorization : acute physical and psychological stressors elicit distinctive recruitment patterns in the amygdala and in medullary noradrenergic cell groups

It has been hypothesized that the brain categorizes stressors and utilizes neural response pathways that vary in accordance with the assigned category. If this is true, stressors should elicit patterns of neuronal activation within the brain that are category-specific. Data from previous immediate&ndash;early gene expression mapping studies have hinted that this is the case, but interstudy differences in methodology render conclusions tenuous. In the present study, immunolabelling for the expression of c-fos was used as a marker of neuronal activity elicited in the rat brain by haemorrhage, immune challenge, noise, restraint and forced swim. All stressors elicited c-fos expression in 25&ndash;30% of hypothalamic paraventricular nucleus corticotrophin-releasing-factor cells, suggesting that these stimuli were of comparable strength, at least with regard to their ability to activate the hypothalamic&ndash;pituitary&ndash;adrenal axis. In the amygdala, haemorrhage and immune challenge both elicited c-fos expression in a large number of neurons in the central nucleus of the amygdala, whereas noise, restraint and forced swim primarily elicited recruitment of cells within the medial nucleus of the amygdala. In the medulla, all stressors recruited similar numbers of noradrenergic (A1 and A2) and adrenergic (C1 and C2) cells. However, haemorrhage and immune challenge elicited c-fos expression in subpopulations of A1 and A2 noradrenergic cells that were significantly more rostral than those recruited by noise, restraint or forced swim. The present data support the suggestion that the brain recognizes at least two major categories of stressor, which we have referred to as &lsquo;physical&rsquo; and &lsquo;psychological&rsquo;. Moreover, the present data suggest that the neural activation footprint that is left in the brain by stressors can be used to determine the category to which they have been assigned by the brain.<br /

A satisfação do usuário em hospital universitário User satisfaction at a university hospital

São apresentados resultados de uma pesquisa exploratória da satisfação/insatisfação de 158 pacientes que recorreram a um Hospital Universitário (HUPE) para consulta inicial. As entrevistas foram feitas por alunos do primeiro ano, como parte de projeto de inserção precoce do mesmo com a prática médica, acompanhando pacientes como observadores. Foi utilizado questionário que cobriu os vários aspectos do problema: variáveis sócio-demográficas, arte do cuidado, resolutividade da consulta médica, sugestões de melhoria dos serviços. Tanto alunos/observadores como os usuários conseguiram perceber com precisão os problemas do processo do atendimento (recepção, matrícula, consulta, enfermagem, serviço social, farmácia, exames complementares) mas houve divergência de opinião entre vários aspectos da satisfação/insatisfação entre alunos e usuários, provavelmente devido às origens sociais diferentes e expectativas diversas.<br>The results of a research project into the level of satisfaction/dissatisfaction of 158 first-time patients attending by an University hospital, Brazil, are presented. The interviews were carried out by first year medical students as part of a comprehensive project concerned with the restructuring of the Medical Curriculum. Its prime objective was to expose the students to patients/consumers as early as possible in their studies. After an introductory training program, the students asked the patients arriving at the hospital out-patient clinic for permission to observe them throughout the attendance given. A questionnaire was used which covered the various aspects of the consumers relationship with a medical institution (socio-economic variables, "art of care", outcome of the medical encounter and suggestions for improvement). Both patients and students were able to perceive the different problems that patients confront in the course of their dealings with a medical institution (reception, registration, nursing, social service and medical attention). The data showed a difference of opinion between students and patients regarding several aspects of the satisfaction/dissatisfaction items, partly because of their different social class status and parthy due to the different expectations regarding medical care

The central nucleus of the amygdala: a conduit for modulation of HPA axis responses to an immune challenge?

Physical stressors such as infection, inflammation and tissue injury elicit activation of the hypothalamic-pituitary-adrenal (HPA) axis. This response has significant implications for both immune and central nervous system function. Investigations in rats into the neural substrates responsible for HPA axis activation to an immune challenge have predominantly utilized an experimental paradigm involving the acute administration of the pro-inflammatory cytokine interleukin-1β (IL-1β). It is well recognized that medial parvocellular corticotrophin-releasing factor cells of the paraventricular nucleus (mPVN CRF) are critical in generating HPA axis responses to an immune challenge but little is known about how peripheral immune signals can activate and/or modulate the mPVN CRF cells. Studies that have examined the afferent control of the mPVN CRF cell response to systemic IL-1β have centred largely on the inputs from brainstem catecholamine cells. However, other regulatory neuronal populations also merit attention and one such region is a component of the limbic system, the central nucleus of the amygdala (CeA). A large number of CeA cells are recruited following systemic IL-1β administration and there is a significant body of work indicating that the CeA can influence HPA axis function. However, the contribution of the CeA to HPA axis responses to an immune challenge is only just beginning to be addressed. This review examines three aspects of HPA axis control by systemic IL-1β: (i) Whether the CeA has a role in generating HPA axis responses to systemic IL-1β, (ii) the identity of the neural connections between the CeA and mPVN CRF cells that might be important to HPA axis responses and (iii) the mechanisms by which systemic IL-1β triggers the recruitment of CeA cells