Testing the Applicability of a Checklist-Based Startle Management Method in the Simulator

Several checklist-based methods have been proposed to help pilots manage startle in unexpected situations. In the current experiment, we tested how pilots reacted to using such a method, which featured the mnemonic COOL: Calm down – Observe – Outline – Lead. Using a motion-based simulator outfitted with a non-linear aerodynamic model of a small twin-propeller aircraft, twelve pilots practiced using the COOL method before performing four test scenarios involving startling events. Application of the full method in the test scenarios was high (90-100%), and pilots rated the method on average as useful (4 on a 1-5 point Likert scale). The first two steps of the method were seen as the “core” of the method. However, pilots also displayed difficulty with prioritizing dealing with immediate threats over executing the method. The results are promising, but they also warn us to be cautious when introducing a startle management method

Active Wnt signaling in response to cardiac injury

Although the contribution of Wnt signaling in infarct healing is suggested, its exact role after myocardial infarction (MI) still needs to be unraveled. We evaluated the cardiac presence of active Wnt signaling in vivo following MI, and investigated in which cell types active Wnt signaling was present by determining Axin2 promoter-driven LacZ expression. C57BL/6 Axin2-LacZ reporter mice were sacrificed at days 0, 1, 3, 7, 14, and 21 after LAD ligation. Hearts were snap-frozen for immunohistochemistry (IHC) or enzymatically digested to obtain a single cell suspension for flow cytometric analysis. For both FACS and IHC, samples were stained for β-galactosidase and antibodies against Sca-1, CD31, ckit, and CD45. Active Wnt signaling increased markedly in the myocardium, from 7 days post-MI onwards. Using Sca-1 and CD31, to identify progenitor and endothelial cells, a significant increase in LacZ+ cells was found at 7 and 14 days post-MI. LacZ+ cells also increased in the ckit+ and CD45+ cell population. IHC revealed LacZ+ cells co-expressing Sca, CD31, CD45, vWF, and αSMA in the border zone and the infarcted area. Wnt signaling increased significantly after MI in Sca+- and CD31+-expressing cells, suggesting involvement of Wnt signaling in resident Sca+ progenitor cells, as well as endothelial cells. Moreover, active Wnt signaling was present in ckit+ cells, leukocytes, and fibroblast. Given its broad role during the healing phase after cardiac injury, additional research seems warranted before a therapeutic approach on Wnt to enhance cardiac regeneration can be carried out safely

Effect of novel technology-enabled multidimensional physical activity feedback in primary care patients at risk of chronic disease – the MIPACT study: A randomised controlled trial

© 2020 The Author(s). Background: Technological progress has enabled the provision of personalised feedback across multiple dimensions of physical activity that are important for health. Whether this multidimensional approach supports physical activity behaviour change has not yet been examined. Our objective was to examine the effectiveness of a novel digital system and app that provided multidimensional physical activity feedback combined with health trainer support in primary care patients identified as at risk of chronic disease. Methods: MIPACT was a parallel-group, randomised controlled trial that recruited patients at medium (≥10 and minimum clinically important difference, MCID). However, there was profound physical activity multidimensionality, and only a small proportion (5%) of patients had consistently low physical activity across all dimensions. Conclusion: In patients at risk of cardiovascular disease and/or type II diabetes, MIPACT did not increase mean physical activity. Using a sophisticated multidimensional digital approach revealed enormous heterogeneity in baseline physical activity in primary care patients, and practitioners may need to screen for low physical activity across dimensions rather than rely on disease-risk algorithms that are heavily influenced by age. Trial registration: This trial is registered with the ISRCTN registry (ISRCTN18008011; registration date 31 July 2013)

Caveolin-1 Influences Vascular Protease Activity and Is a Potential Stabilizing Factor in Human Atherosclerotic Disease

Caveolin-1 (Cav-1) is a regulatory protein of the arterial wall, but its role in human atherosclerosis remains unknown. We have studied the relationships between Cav-1 abundance, atherosclerotic plaque characteristics and clinical manisfestations of atherosclerotic disease.We determined Cav-1 expression by western blotting in atherosclerotic plaques harvested from 378 subjects that underwent carotid endarterectomy. Cav-1 levels were significantly lower in carotid plaques than non-atherosclerotic vascular specimens. Low Cav-1 expression was associated with features of plaque instability such as large lipid core, thrombus formation, macrophage infiltration, high IL-6, IL-8 levels and elevated MMP-9 activity. Clinically, a down-regulation of Cav-1 was observed in plaques obtained from men, patients with a history of myocardial infarction and restenotic lesions. Cav-1 levels above the median were associated with absence of new vascular events within 30 days after surgery [0% vs. 4%] and a trend towards lower incidence of new cardiovascular events during longer follow-up. Consistent with these clinical data, Cav-1 null mice revealed elevated intimal hyperplasia response following arterial injury that was significantly attenuated after MMP inhibition. Recombinant peptides mimicking Cav-1 scaffolding domain (Cavtratin) reduced gelatinase activity in cultured porcine arteries and impaired MMP-9 activity and COX-2 in LPS-challenged macrophages. Administration of Cavtratin strongly impaired flow-induced expansive remodeling in mice.This is the first study that identifies Cav-1 as a novel potential stabilizing factor in human atherosclerosis. Our findings support the hypothesis that local down-regulation of Cav-1 in atherosclerotic lesions contributes to plaque formation and/or instability accelerating the occurrence of adverse clinical outcomes. Therefore, given the large number of patients studied, we believe that Cav-1 may be considered as a novel target in the prevention of human atherosclerotic disease and the loss of Cav-1 may be a novel biomarker of vulnerable plaque with prognostic value

J Am Heart Assoc

Background Research links blood pressure variability (BPV) with stroke; however, the association with cerebral small‐vessel disease (CSVD) remains unclear. As BPV and mean blood pressure are interrelated, it remains uncertain whether BPV adds additional information to understanding cerebrovascular morphological characteristics. Methods and Results A systematic review was performed from inception until March 3, 2019. Eligibility criteria included population, adults without stroke (<4 weeks); exposure, BPV quantified by any metric over any duration; comparison, (1) low versus high or mean BPV and (2) people with versus without CSVD; and outcomes, (1) CSVD as subcortical infarct, lacunae, white matter hyperintensities, cerebral microbleeds, or enlarged perivascular spaces; and (2) standardized mean difference in BPV. A total of 27 articles were meta‐analyzed, comprising 12 309 unique brain scans. A total of 31 odds ratios (ORs) were pooled, indicating that higher systolic BPV was associated with higher odds for CSVD (OR, 1.27; 95% CI, 1.14–1.42; I2=85%) independent of mean systolic pressure. Likewise, higher diastolic BPV was associated with higher odds for CSVD (OR, 1.30; 95% CI, 1.14–1.48; I2=53%) independent of mean diastolic pressure. There was no evidence of a pairwise interaction between systolic/diastolic and BPV/mean ORs (P=0.47), nor a difference between BPV versus mean pressure ORs (P=0.58). Fifty‐four standardized mean differences were pooled and provided similar results for pairwise interaction (P=0.38) and difference between standardized mean differences (P=0.70). Conclusions On the basis of the available studies, BPV was associated with CSVD independent of mean blood pressure. However, more high‐quality longitudinal data are required to elucidate whether BPV contributes unique variance to CSVD morphological characteristics