Multi-omic analysis of the effects of low frequency ventilation during cardiopulmonary bypass surgery.

BACKGROUND: Heart surgery with cardio-pulmonary bypass (CPB) is associated with lung ischemia leading to injury and inflammation. It has been suggested this is a result of the lungs being kept deflated throughout the duration of CPB. Low frequency ventilation (LFV) during CPB has been proposed to reduce lung dysfunction. METHODS: We used a semi-biased multi-omic approach to analyse lung biopsies taken before and after CPB from 37 patients undergoing coronary artery bypass surgery randomised to both lungs left collapsed or using LFV for the duration of CPB. We also examined inflammatory and oxidative stress markers from blood samples from the same patients. RESULTS: 30 genes were induced when the lungs were left collapsed and 80 by LFV. Post-surgery 26 genes were significantly higher in the LFV vs. lungs left collapsed, including genes associated with inflammation (e.g. IL6 and IL8) and hypoxia/ischemia (e.g. HIF1A, IER3 and FOS). Relatively few changes in protein levels were detected, perhaps reflecting the early time point or the importance of post-translational modifications. However, pathway analysis of proteomic data indicated that LFV was associated with increased "cellular component morphogenesis" and a decrease in "blood circulation". Lipidomic analysis did not identify any lipids significantly altered by either intervention. DISCUSSION: Taken together these data indicate the keeping both lungs collapsed during CPB significantly induces lung damage, oxidative stress and inflammation. LFV during CPB increases these deleterious effects, potentially through prolonged surgery time, further decreasing blood flow to the lungs and enhancing hypoxia/ischemia

Cognitive symptoms facilitatory for diagnoses in neuropsychiatric disorders: Executive functions and locus of control

Cognitive symptoms, considered in conjunction both with their regional brain and biomarkers as well as affective, attributional and neurode-velopmental components, demonstate ever-increasing complexity to facilitate conceptualization yet, unavoidably, bedevil diagnosis in neuropsychiatry even before considerations of the enigmatic processes in memory, such as executive function and working memory, are drawn into the myriads of equations that await remedial interpretations. Prefrontal and limbic regions of the brain are involved in a diversity of expressions of cognition, normal or dysfunctional, at synaptic, intracellular and molecular levels that mobilize a concatenation of signaling entities. Serotoninergic neurotransission at prefrontal regions directs cogntive-affective entities that mediate decision-making and goal-directed behaviour. Clinical, non-clinical and basic studies challenge attempts to consolidate the multitude of evidence in order to obtain therapeutic notions to alleviate the disordered status of the diagnosed and yet-to-be diagnosed individuals. Locus of control, a concept of some utility in health-seeking procedures, is examined in three self-report studies from the perspective of a cognitive-emotional situation through observations of ordinary, \u27healthy\u27 young and middle-aged individuals, to assess the predictors of internal and external locus of control. A notion based on high level executive functioning in the dorsolateral prefrontal cortex (DLPFC) in individuals characterised by internal locus of control is contrasted with a hypofunctional executive DLPFC, characterising individuals that express an external locus of control, is discussed