The 10th Biennial Hatter Cardiovascular Institute workshop: cellular protection—evaluating new directions in the setting of myocardial infarction, ischaemic stroke, and cardio-oncology

Due to its poor capacity for regeneration, the heart is particularly sensitive to the loss of contractile cardiomyocytes. The onslaught of damage caused by ischaemia and reperfusion, occurring during an acute myocardial infarction and the subsequent reperfusion therapy, can wipe out upwards of a billion cardiomyocytes. A similar program of cell death can cause the irreversible loss of neurons in ischaemic stroke. Similar pathways of lethal cell injury can contribute to other pathologies such as left ventricular dysfunction and heart failure caused by cancer therapy. Consequently, strategies designed to protect the heart from lethal cell injury have the potential to be applicable across all three pathologies. The investigators meeting at the 10th Hatter Cardiovascular Institute workshop examined the parallels between ST-segment elevation myocardial infarction (STEMI), ischaemic stroke, and other pathologies that cause the loss of cardiomyocytes including cancer therapeutic cardiotoxicity. They examined the prospects for protection by remote ischaemic conditioning (RIC) in each scenario, and evaluated impasses and novel opportunities for cellular protection, with the future landscape for RIC in the clinical setting to be determined by the outcome of the large ERIC-PPCI/CONDI2 study. It was agreed that the way forward must include measures to improve experimental methodologies, such that they better reflect the clinical scenario and to judiciously select combinations of therapies targeting specific pathways of cellular death and injury

Inhibition of MLC Phosphorylation Restricts Replication of Influenza Virus—A Mechanism of Action for Anti-Influenza Agents

Influenza A viruses are a severe threat worldwide, causing large epidemics that kill thousands every year. Prevention of influenza infection is complicated by continuous viral antigenic changes. Newer anti-influenza agents include MEK/ERK and protein kinase C inhibitors; however, the downstream effectors of these pathways have not been determined. In this study, we identified a common mechanism for the inhibitory effects of a significant group of anti-influenza agents. Our studies showed that influenza infection activates a series of signaling pathways that converge to induce myosin light chain (MLC) phosphorylation and remodeling of the actin cytoskeleton. Inhibiting MLC phosphorylation by blocking RhoA/Rho kinase, phospholipase C/protein kinase C, and HRas/Raf/MEK/ERK pathways with the use of genetic or chemical manipulation leads to the inhibition of influenza proliferation. In contrast, the induction of MLC phosphorylation enhances influenza proliferation, as does activation of the HRas/Raf/MEK/ERK signaling pathway. This effect is attenuated by inhibiting MLC phosphorylation. Additionally, in intracellular trafficking studies, we found that the nuclear export of influenza ribonucleoprotein depends on MLC phosphorylation. Our studies provide evidence that modulation of MLC phosphorylation is an underlying mechanism for the inhibitory effects of many anti-influenza compounds

Iron Behaving Badly: Inappropriate Iron Chelation as a Major Contributor to the Aetiology of Vascular and Other Progressive Inflammatory and Degenerative Diseases

The production of peroxide and superoxide is an inevitable consequence of aerobic metabolism, and while these particular "reactive oxygen species" (ROSs) can exhibit a number of biological effects, they are not of themselves excessively reactive and thus they are not especially damaging at physiological concentrations. However, their reactions with poorly liganded iron species can lead to the catalytic production of the very reactive and dangerous hydroxyl radical, which is exceptionally damaging, and a major cause of chronic inflammation. We review the considerable and wide-ranging evidence for the involvement of this combination of (su)peroxide and poorly liganded iron in a large number of physiological and indeed pathological processes and inflammatory disorders, especially those involving the progressive degradation of cellular and organismal performance. These diseases share a great many similarities and thus might be considered to have a common cause (i.e. iron-catalysed free radical and especially hydroxyl radical generation). The studies reviewed include those focused on a series of cardiovascular, metabolic and neurological diseases, where iron can be found at the sites of plaques and lesions, as well as studies showing the significance of iron to aging and longevity. The effective chelation of iron by natural or synthetic ligands is thus of major physiological (and potentially therapeutic) importance. As systems properties, we need to recognise that physiological observables have multiple molecular causes, and studying them in isolation leads to inconsistent patterns of apparent causality when it is the simultaneous combination of multiple factors that is responsible. This explains, for instance, the decidedly mixed effects of antioxidants that have been observed, etc...Comment: 159 pages, including 9 Figs and 2184 reference

Factors associated with a diabetes diagnosis and late diabetes diagnosis for males and females

Aims: To examine the factors associated with diabetes, a late diabetes diagnosis, and whether these factors are different for males and females. Methods: Cross-sectional study including 7101 individuals aged ≥25 years in Newfoundland and Labrador, Canada (466 with diabetes; 332 diagnosed late). Logistic regression analysis was used to determine the factors associated with a diabetes diagnosis and late diabetes diagnosis. Results: For males, overweight/obesity (HR, 1.35; 95% CI, 1.06–1.72) was positively associated with diabetes while being a regular/occasional drinker (HR, 0.53; 95% CI, 0.32–0.88) was inversely associated with diabetes. Living in a rural area (HR, 1.47; 95% CI, 1.01–2.15), receiving social assistance (HR, 2.80; 95% CI, 1.52–5.15), having poor self perceived health (HR, 2.06; 95% CI, 1.32–3.21), and considering most days stressful (HR, 1.45; 95% CI, 1.01–2.10) were positively associated with diabetes for females. No factors were significantly associated with a late diabetes diagnosis for males. Having a low education (OR, 0.33; 95% CI, 0.11–0.99) was inversely associated with a late diabetes diagnosis for females. Conclusions: Different factors are associated with diabetes for males and females. Disadvantaged females appear to be at the greatest risk. The factors associated with a late diabetes diagnosis were also different for males and females. Females with lower education levels are diagnosed with diabetes earlier than females with higher education levels. Certain risk factors appear to impact males and females differently and more research is needed on how males and females develop diabetes and when they are diagnosed

A rare case of symptomatic vascular ring

In this paper, we describe a rare case of double aortic arch with dominant right arch with focal narrowing of the distal left arch and descendent aorta's dilatation, associated with pulmonary embolism and left subclavian steal syndrome, found in a 59-year-old woman with a history of dysphagia, chest discomfort, and left arm claudication. Diagnosis of this condition was made with a sub-optimal pulmonary CT-angiography with a combination of characteristic features of double aortic arch and vascular rings. Being aware of these conditions is crucial to avoid misclassification and surgical and endovascular complications

93; Personal non-commercial use only

ABSTRACT. This review seeks to update the state of the art of axial psoriatic arthritis (axPsA). The definition and assessment of axPsA can be problematic because no agreement and no definitive data on this topic have been published, resulting in uncertainty as to the best approach to deal with these patients. A few recent scientific reports show new data on the possible coincidence of diffuse idiopathic skeletal hyperostosis and axPsA, as well as on the radiological assessment as measured with the validated instruments for axPsA. Moreover, the role of magnetic resonance imaging has also been evaluated for this intriguing subset. All data confirmed that radiological assessment is a useful tool to detect typical findings of axPsA, while other imaging techniques remain to be validated. Finally, there is no evidence to support treatment of axPsA with traditional disease-modifying antirheumatic drugs, while a "leap" to biologic agents is the only treatment after failure with nonsteroidal antiinflammatory drugs