Microarray Meta-Analysis and Cross-Platform Normalization: Integrative Genomics for Robust Biomarker Discovery.

The diagnostic and prognostic potential of the vast quantity of publicly-available microarray data has driven the development of methods for integrating the data from different microarray platforms. Cross-platform integration, when appropriately implemented, has been shown to improve reproducibility and robustness of gene signature biomarkers. Microarray platform integration can be conceptually divided into approaches that perform early stage integration (cross-platform normalization) versus late stage data integration (meta-analysis). A growing number of statistical methods and associated software for platform integration are available to the user, however an understanding of their comparative performance and potential pitfalls is critical for best implementation. In this review we provide evidence-based, practical guidance to researchers performing cross-platform integration, particularly with an objective to discover biomarkers.

Lung-injured patients do not need a specialized rehabilitation program: ICUAW as a case study.

An episode of critical illness is transformative. Patients suffer important new nerve, brain, and muscle injury. The spectrum of morbidity varies according to individual risks, but prevalent disabilities transcend diagnostic groupings. In the context of intensive care unit-acquired weakness (ICUAW), each patient who enters the ICU will begin to degrade muscle through upregulation of different proteolytic pathways, and, although the inciting stimulus, or its magnitude, may differ somewhat across patients, the result is the same. This argues for an approach to rehabilitation that is etiologically neutral and based on an understanding of molecular pathophysiology that can be mapped to functional outcome and tailored to individual need.

Cell therapy in acute lung injury / Terapia celular em lesão pulmonar aguda

Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) continue to be major causes of morbidity and mortality in critically ill patients. Investigations indicate that stem cells represent a viable therapeutic option for patients with ALI/ARDS. Recent studies have described the mechanistic pathways of stem cells in critical illness. This article reviews the use of stem cells as a potential for exogenous cell-based therapy in ALI. Further studies are needed in order to fully elucidate the mechanisms involved in the immunomodulatory activities of stem cells, as well as in their mobilisation and tissue engraftment.

A lesão pulmonar aguda (LPA) e a síndrome do desconforto respiratório agudo (SDRA) permanecem como uma das principais causas de morbidade e mortalidade em pacientes internados em unidades de terapia intensiva. Diversos estudos demonstram que as células-tronco podem representar uma opção terapêutica viável para pacientes com LPA/SDRA. Estudos recentes têm descrito as vias mecanísticas das células-tronco em doenças graves. Este artigo faz uma revisão crítica do uso de células-tronco em LPA como um potencial para a terapia celular com utilização de células exógenas. Mais estudos são necessários para delinear completamente os mecanismos responsáveis pelas características imunomoduladoras das células-tronco, além de sua capacidade de movimentação e de integração a tecidos.

Neuroimmune regulation of ventilator-induced lung injury.

RATIONALE: Ventilator-induced lung injury (VILI) contributes to the mortality in patients with acute lung injury by increasing inflammation. Recent evidence suggests that stimulation of the cholinergic antiinflammatory pathway may be an attractive way to attenuate inflammatory injury. OBJECTIVES: To determine the role of vagus nerve signaling in VILI and establish whether stimulation of the vagus reflex can mitigate VILI. METHODS: We performed bilateral vagotomy in a mouse model of high-tidal volume-induced lung injury. We performed pharmacological and electrical vagus nerve stimulation in a rat model of VILI following ischemia/reperfusion injury. To determine the contribution of the alpha 7 acetylcholine nicotinic receptor to pulmonary cell injury, we exposed human bronchial epithelial cells to cyclic stretch in the presence of specific agonist or antagonist of the alpha 7 receptor. MEASUREMENTS AND MAIN RESULTS: Vagotomy exacerbates lung injury from VILI in mice as demonstrated by increased wet-to-dry ratio, infiltration of neutrophils, and increased IL-6. Vagal stimulation attenuates lung injury in rats after ischemia/reperfusion injury ventilated with high-volume strategies. Treatment of both mice and rats with the vagus mimetic drug semapimod resulted in decreased lung injury. Vagotomy also increased pulmonary apoptosis, whereas vagus stimulation (electrical and pharmacological) attenuated VILI-induced apoptosis. In vitro studies suggest that vagus-dependent effects on inflammation and apoptosis are mediated via the α7 nicotinc acetylcholine receptor-dependent effects on cyclic stretch-dependent signaling pathways c-jun N-terminal kinase and tumor necrosis factor receptor superfamily, member 6. CONCLUSIONS: Stimulation of the cholinergic antiinflammatory reflex may represent a promising alternative for the treatment of VILI.

Bench-to-bedside review: Biotrauma and modulation of the innate immune response.

The innate immune network is responsible for coordinating the initial defense against potentially noxious stimuli. This complex system includes anatomical, physical and chemical barriers, effector cells and circulating molecules that direct component and system interactions. Besides the direct effects of breaching pulmonary protective barriers, cyclic stretch generated during mechanical ventilation (MV) has been implicated in the modulation of the innate immunity. Evidence from recent human trials suggests that controlling MV-forces may significantly impact outcome in acute respiratory distress syndrome. In this paper, we explore the pertinent evidence implicating biotrauma caused by cyclic MV and its effect on innate immune responses.