Plasma from Volunteers Breathing Helium Reduces Hypoxia-Induced Cell Damage in Human Endothelial Cells-Mechanisms of Remote Protection Against Hypoxia by Helium.

PurposeRemote ischemic preconditioning protects peripheral organs against prolonged ischemia/reperfusion injury via circulating protective factors. Preconditioning with helium protected healthy volunteers against postischemic endothelial dysfunction. We investigated whether plasma from helium-treated volunteers can protect human umbilical vein endothelial cells (HUVECs) against hypoxia in vitro through release of circulating of factors.MethodsHealthy male volunteers inhaled heliox (79% helium, 21% oxygen) or air for 30 min. Plasma was collected at baseline, directly after inhalation, 6 h and 24 h after start of the experiment. HUVECs were incubated with either 5% or 10% of the plasma for 1 or 2 h and subjected to enzymatically induced hypoxia. Cell damage was measured by LDH content. Furthermore, caveolin 1 (Cav-1), hypoxia-inducible factor (HIF1α), extracellular signal-regulated kinase (ERK)1/2, signal transducer and activator of transcription (STAT3) and endothelial nitric oxide synthase (eNOS) were determined.ResultsPrehypoxic exposure to 10% plasma obtained 6 h after helium inhalation decreased hypoxia-induced cell damage in HUVEC. Cav-1 knockdown in HUVEC abolished this effect.ConclusionsPlasma of healthy volunteers breathing helium protects HUVEC against hypoxic cell damage, possibly involving circulating Cav-1

Effect of helium pre- or postconditioning on signal transduction kinases in patients undergoing coronary artery bypass graft surgery

Background: The noble gas helium induces pre- and postconditioning in animals and humans. Volatile anesthetics induce cardioprotection in humans undergoing coronary artery bypass graft (CABG) surgery. We hypothesized that helium induces pre-and postconditioning in CABG-patients, affecting signaling molecules protein kinase C-epsilon (PKC-epsilon), p38 mitogen activated protein kinase (p38 MAPK), extracellular signal-regulated kinase 1/2 (ERK-1/2) and heat shock protein 27 (HSP-27) within cardiac tissue, and reducing postoperative troponin levels. Methods: After ethical approval and informed consent, 125 elective patients undergoing CABG surgery were randomised into this prospective, placebo controlled, investigator blinded, parallel arm single-centre study. Helium preconditioning (3 x 5 min of 70 % helium and 30 % oxygen) was applied before aortic cross clamping; postconditioning (15 min of helium) was applied before release of the aortic cross clamp. Signaling molecules were measured in right atrial appendix specimens. Troponin-T was measured at 4, 12, 24 and 48 h postoperatively. Results: Baseline characteristics of all groups were similar. Helium preconditioning did not significantly alter the primary outcome (molecular levels of kinases PKC-e and HSP-27, ratio of activated p38 MAPK or ERK 1/2). Postoperative troponin T was 11 arbitrary units [5, 31; area-under-the-curve (interquartile range)] for controls, and no statistically significant changes were observed after helium preconditioning [He-pre: 11 (6, 18)], helium postconditioning [He-post: 11 (8, 15)], helium pre-and postconditioning [He-PP: 14 (6, 20)] and after sevoflurane preconditioning [APC: 12 (8, 24), p = 0.13]. No adverse effects related to study treatment were observed in this study. Conclusions: No effect was observed of helium preconditioning, postconditioning or the combination thereof on activation of p38 MAPK, ERK 1/2 or levels of HSP27 and PKC-e in the human heart. Helium pre-and postconditioning did not affect postoperative troponin release in patients undergoing CABG surgery

Assessment of reward-related brain function after a single-dose of oxytocin in autism: A randomized controlled trial

Background Autism spectrum disorder (ASD) is characterized by difficulties in social communication and interaction, which have been related to atypical neural processing of rewards, especially in the social domain. Since intranasal oxytocin has been shown to modulate activation of the brain’s reward circuit, oxytocin might ameliorate the processing of social rewards in ASD and thus improve social difficulties. Methods In this randomized, double-blind, placebo-controlled, crossover fMRI study, we examined effects of a 24 IU dose of intranasal oxytocin on reward-related brain function in 37 men with ASD without intellectual impairment and 37 age- and IQ-matched control participants. Participants performed an incentive delay task that allows the investigation of neural activity associated with the anticipation and receipt of monetary and social rewards. Results Non-significant tests suggested that oxytocin did not influence neural processes related to the anticipation of social or monetary rewards in either group. Complementary Bayesian analyses indicated moderate evidence for a null model, relative to an alternative model. Our results are inconclusive regarding possible oxytocin effects on amygdala responsiveness to social rewards during reward consumption. There were no significant differences in reward-related brain function between the two groups under placebo. Conclusions Our results do not support the hypothesis that intranasal oxytocin generally enhances activation of reward-related neural circuits in men with and without ASD

Driving pressure during general anesthesia for open abdominal surgery (DESIGNATION) : study protocol of a randomized clinical trial

Background Intraoperative driving pressure (Delta P) is associated with development of postoperative pulmonary complications (PPC). When tidal volume (V-T) is kept constant, Delta P may change according to positive end-expiratory pressure (PEEP)-induced changes in lung aeration. Delta P may decrease if PEEP leads to a recruitment of collapsed lung tissue but will increase if PEEP mainly causes pulmonary overdistension. This study tests the hypothesis that individualized high PEEP, when compared to fixed low PEEP, protects against PPC in patients undergoing open abdominal surgery. Methods The "Driving prESsure durIng GeNeral AnesThesIa for Open abdomiNal surgery trial" (DESIGNATION) is an international, multicenter, two-group, double-blind randomized clinical superiority trial. A total of 1468 patients will be randomly assigned to one of the two intraoperative ventilation strategies. Investigators screen patients aged >= 18 years and with a body mass index <= 40 kg/m(2), scheduled for open abdominal surgery and at risk for PPC. Patients either receive an intraoperative ventilation strategy with individualized high PEEP with recruitment maneuvers (RM) ("individualized high PEEP") or one in which PEEP of 5 cm H2O without RM is used ("low PEEP"). In the "individualized high PEEP" group, PEEP is set at the level at which Delta P is lowest. In both groups of the trial, V-T is kept at 8 mL/kg predicted body weight. The primary endpoint is the occurrence of PPC, recorded as a collapsed composite of adverse pulmonary events. Discussion DESIGNATION will be the first randomized clinical trial that is adequately powered to compare the effects of individualized high PEEP with RM versus fixed low PEEP without RM on the occurrence of PPC after open abdominal surgery. The results of DESIGNATION will support anesthesiologists in their decisions regarding PEEP settings during open abdominal surgery

Anxiety is not enough to drive me away: A latent profile analysis on math anxiety and math motivation

Mathematics anxiety (MA) and mathematics motivation (MM) are important multi-dimensional non-cognitive factors in mathematics learning. While the negative relation between global MA and MM is well replicated, the relations between specific dimensions of MA and MM are largely unexplored. The present study utilized latent profile analysis to explore profiles of various aspects of MA (including learning MA and exam MA) and MM (including importance, self-perceived ability, and interest), to provide a more holistic understanding of the math-specific emotion and motivation experiences. In a sample of 927 high school students (13–21 years old), we found 8 distinct profiles characterized by various combinations of dimensions of MA and MM, revealing the complexity in the math-specific emotion-motivation relation beyond a single negative correlation. Further, these profiles differed on mathematics learning behaviors and mathematics achievement. For example, the highest achieving students reported modest exam MA and high MM, whereas the most engaged students were characterized by a combination of high exam MA and high MM. These results call for the need to move beyond linear relations among global constructs to address the complexity in the emotion-motivation-cognition interplay in mathematics learning, and highlight the importance of customized intervention for these heterogeneous groups

Effect of remote ischemic conditioning on atrial fibrillation and outcome after coronary artery bypass grafting (RICO-trial)

Background: Pre- and postconditioning describe mechanisms whereby short ischemic periods protect an organ against a longer period of ischemia. Interestingly, short ischemic periods of a limb, in itself harmless, may increase the ischemia tolerance of remote organs, e.g. the heart (remote conditioning, RC). Although several studies have shown reduced biomarker release by RC, a reduction of complications and improvement of patient outcome still has to be demonstrated. Atrial fibrillation (AF) is one of the most common complications after coronary artery bypass graft surgery (CABG), affecting 27-46% of patients. It is associated with increased mortality, adverse cardiovascular events, and prolonged in-hospital stay. We hypothesize that remote ischemic pre- and/or post-conditioning reduce the incidence of AF following CABG, and improve patient outcome.Methods/design: This study is a randomized, controlled, patient and investigator blinded multicenter trial. Elective CABG patients are randomized to one of the following four groups: 1) control, 2) remote ischemic preconditioning, 3) remote ischemic postconditioning, or 4) remote ischemic pre- and postconditioning. Remote conditio

Metabolic acidosis may be as protective as hypercapnic acidosis in an ex-vivo model of severe ventilator-induced lung injury: a pilot study

<p>Abstract</p> <p>Background</p> <p>There is mounting experimental evidence that hypercapnic acidosis protects against lung injury. However, it is unclear if acidosis <it>per se </it>rather than hypercapnia is responsible for this beneficial effect. Therefore, we sought to evaluate the effects of hypercapnic (respiratory) versus normocapnic (metabolic) acidosis in an ex vivo model of ventilator-induced lung injury (VILI).</p> <p>Methods</p> <p>Sixty New Zealand white rabbit ventilated and perfused heart-lung preparations were used. Six study groups were evaluated. Respiratory acidosis (RA), metabolic acidosis (MA) and normocapnic-normoxic (Control - C) groups were randomized into high and low peak inspiratory pressures, respectively. Each preparation was ventilated for 1 hour according to a standardized ventilation protocol. Lung injury was evaluated by means of pulmonary edema formation (weight gain), changes in ultrafiltration coefficient, mean pulmonary artery pressure changes as well as histological alterations.</p> <p>Results</p> <p>HPC group gained significantly greater weight than HPMA, HPRA and all three LP groups (P = 0.024), while no difference was observed between HPMA and HPRA groups regarding weight gain. Neither group differ on ultrafiltration coefficient. HPMA group experienced greater increase in the mean pulmonary artery pressure at 20 min (P = 0.0276) and 40 min (P = 0.0012) compared with all other groups. Histology scores were significantly greater in HP vs. LP groups (p < 0.001).</p> <p>Conclusions</p> <p>In our experimental VILI model both metabolic acidosis and hypercapnic acidosis attenuated VILI-induced pulmonary edema implying a mechanism other than possible synergistic effects of acidosis with CO2 for VILI attenuation.</p