Global longitudinal strain at rest predicts significant coronary artery stenosis in patients with peripheral arterial disease

Abstract Funding Acknowledgements Type of funding sources: None. Background Critical peripheral artery disease (PAD) is expression of systemic chronic atherosclerosis, it being often associated with cardiovascular events. The assessment of global longitudinal strain (GLS) at rest by speckle tracking echocardiography could be useful to unmask significant coronary artery disease (CAD) in asymptomatic PAD patients. Purpose To determine whether resting GLS is able to predict significant coronary artery stenosis in PAD patients selected for peripheral or carotid angiography. Methods One-hundred three clinically relevant PAD patients (M/F = 76/27, age = 66.8 ± 10,2 years, 72 with significant lower limb artery stenosis and 31 with carotid artery stenosis ≥50%), asymptomatic for CAD, underwent standard echo-Doppler exam at rest, comprehensive of GLS analysis, prior peripheral and coronary angiography. Information on cardiovascular (CV) risk factors and comorbidities were collected. Patients with know CAD and previous myocardial infarction, left ventricular (LV) ejection fraction < 50% and inadequate echocardiographic imaging were excluded. According to the results of coronary angiography, patients were divided in two groups: with significant coronary artery stenosis (>50% of obstruction. n = 73) and without significant coronary artery lesions (n = 30). Results No intergroup difference in the prevalence of CV risk factors and comorbidities was found. Age, body mass index and blood pressure were comparable between the two groups. LV ejection fraction (59.9 ± 4.2% in patients with significant coronary stenosis vs. 60.2 ± 4.7% in those without coronary stenosis, p = 0.75) and wall motion score index (1.02 ± 0.09 vs 1.03 ± 0.09 respectively, p = 0.67) did not differ significantly. Conversely, GLS was lower in patients with significant coronary artery stenosis than in those without (21.6 ± 2.7% vs. 22.8 ± 2%, p < 0.02) (Figure 1). This difference remained significant comparing the carotid subgroup with coronary stenosis vs. those without (p < 0.05) whereas it did not achieve the statistical significance in patients with lower limb artery lesions (p = 0.42). Conclusion In PAD patients, GLS at rest shoes the capability in identifying patients at higher probability of significant coronary artery stenosis. This involves in particular patients with carotid artery stenosis. GLS might be helpful to select patients who need to extend the peripheral angiographic evaluation to the coronary tree

Developing a ranking methodology for chemical industrial clusters: a multi-criteria decision making approach

The clustering process in the chemical industries is becoming more important due to economic, social and political issues. Clustering means agglomeration of companies in the same geographical area in order to increase the productivity and reduce costs. The birth of agreements between companies allows to arouse their interest in other disciplines different from the socio-economic aspect, as safety and security, to name but few. The first step of the methodology is represented by the safety and security risk assessment, followed by the analysis of the relationships within firms in terms of strategic and operation alliances. In the present study, safety risk should be interpreted as an average dangerousness and, at the same time, security risk as average vulnerability of installations in the cluster’s area. Risk, for this evaluation, will not be a function of frequency and magnitude and it will represent an inclination to damage, the potential of chemical cluster to incur in accident(s)/incident(s). The strong influence of the results obtained before can be analysed with the analytic network process that, with pairwise comparisons, is able to assess which parameters have a major influence among the others. In this tool, comparisons within more than one chemical cluster can be taken into account. The final outcome of this methodology is a ranking of chemical clusters, a classification depending on a large number of criteria covering many aspects of safety and security, but as well considering the existing management and relationship within companies. A simple case study has been built in order to investigate, inside the model of the ANP, benefits, costs and risks associated with the selected chemical clusters

TAp63α induces apoptosis by activating signaling via death receptors and mitochondria

TP63, an important epithelial developmental gene, has significant homology to p53. Unlike p53, the expression of p63 is regulated by two different promoters resulting in proteins with opposite functions: the full-length transcriptionally active TAp63 and the dominant-negative ΔNp63. We investigated the downstream mechanisms by which TAp63α elicits apoptosis. TAp63α directly transactivates the CD95 gene via the p53 binding site in the first intron resulting in upregulation of a functional CD95 death receptor. Stimulation and blocking experiments of the CD95, TNF-R and TRAIL-R death receptor systems revealed that TAp63α can trigger expression of each of these death receptors. Furthermore, our findings demonstrate a link between TAp63α and the mitochondrial apoptosis pathway. TAp63α upregulates expression of proapoptotic Bcl-2 family members like Bax and BCL2L11 and the expression of RAD9, DAP3 and APAF1. Of clinical relevance is the fact that TAp63α is induced by many chemotherapeutic drugs and that inhibiting TAp63 function leads to chemoresistance. Thus, beyond its importance in development and differentiation, we describe an important role for TAp63α in the induction of apoptosis and chemosensitivity