The term “triangle of death” was used for the first time by Senior and Mazza in the journal The Lancet Oncology referring to the eastern area of the Campania Region (Southern Italy) which has one of the worst records of illegal waste dumping practices. In the past decades, many studies have focused on the potential of illegal waste disposal to cause adverse effects on human health in this area. The great heterogeneity in the findings, and the bias in media communication has generated great healthcare doubts, anxieties and alarm. This paper addresses a review of the up-to-date literature on the “triangle of death”, bringing together the available information on the occurrence and severity of health effects related to illegal waste disposal. The Scopus database was searched using the search terms “waste”, “Campania”, “Naples”, “triangle of death” and “human biomonitoring”. Despite the methodological and sampling heterogeneity between the studies, this review examines the evidence from published data concerning cancer incidence, childhood mortality and birth defects, so that the current situation, knowledge gaps and research priorities can be established. The review aims to provide a contribution to the scientific community, and to respond to the concerns of the general population.

Integrin activation generates different signalings in a cell type-dependent manner and stimulates cell proliferation through the Ras/Raf-1/Mek/Erk pathway. In this study, we demonstrate that integrin stimulation by fibronectin (FN), besides activating the Ras/Erk pathway, generates an auxiliary calcium signal that activates calmodulin and the Ca²⁺/calmodulin-dependent protein kinase II (CaMKII). This signal regulates Raf-1 activation by Ras and modulates the FN-stimulated extracellular signal-regulated kinase (Erk-1/2). The binding of soluble FN to integrins induced increase of intracellular calcium concentration associated with phosphorylation and activation of CaMKII. In two different cell lines, inhibition of CaMKII activity by specific inhibitors inhibited Erk-1/2 phosphorylation. Whereas CaMK inhibition affected neither integrin-stimulated Akt phosphorylation nor p21Ras or Mek-1 activity, it was necessary for Raf-1 activity. FN-induced Raf-1 activity was abrogated by the CaMKII specific inhibitory peptide ant-CaNtide. Integrin activation by FN induced the formation of a Raf-1/CaMKII complex, abrogated by inhibition of CaMKII. Active CaMKII phosphorylated Raf-1 in vitro. This is the first demonstration that CaMKII interplays with Raf-1 and regulates Erk activation induced by Ras-stimulated Raf-1. These findings also provide evidence supporting the possible existence of cross-talk between other intracellular pathways involving CaMKII and Raf-1.

Background: The expression of calcium/calmodulin‐dependent kinase IV ( CaMKIV ) was hitherto thought to be confined to the nervous system. However, a recent genome‐wide analysis indicated an association between hypertension and a single‐nucleotide polymorphism ( rs10491334 ) of the human CaMKIV gene ( CaMK4 ) , which suggests a role for this kinase in the regulation of vascular tone. Methods and Results: To directly assess the role of CaMKIV in hypertension, we characterized the cardiovascular phenotype of CaMK4 ^−/− mice. They displayed a typical hypertensive phenotype, including high blood pressure levels, cardiac hypertrophy, vascular and kidney damage, and reduced tolerance to chronic ischemia and myocardial infarction compared with wild‐type littermates. Interestingly, in vitro experiments showed the ability of this kinase to activate endothelial nitric oxide synthase. Eventually, in a population study, we found that the rs10491334 variant associates with a reduction in the expression levels of CaMKIV in lymphocytes from hypertensive patients. Conclusions: Taken together, our results provide evidence that CaMKIV plays a pivotal role in blood pressure regulation through the control of endothelial nitric oxide synthase activity.

The Allergic Rhinitis and its Impact on Asthma (ARIA) initiative commenced during a World Health Organization workshop in 1999. The initial goals were (1) to propose a new allergic rhinitis classification, (2) to promote the concept of multi-morbidity in asthma and rhinitis and (3) to develop guidelines with all stakeholders that could be used globally for all countries and populations. ARIA—disseminated and implemented in over 70 countries globally—is now focusing on the implementation of emerging technologies for individualized and predictive medicine. MASK [MACVIA (Contre les Maladies Chroniques pour un Vieillissement Actif)-ARIA Sentinel NetworK] uses mobile technology to develop care pathways for the management of rhinitis and asthma by a multi-disciplinary group and by patients themselves. An app (Android and iOS) is available in 20 countries and 15 languages. It uses a visual analogue scale to assess symptom control and work productivity as well as a clinical decision support system. It is associated with an inter-operable tablet for physicians and other health care professionals. The scaling up strategy uses the recommendations of the European Innovation Partnership on Active and Healthy Ageing. The aim of the novel ARIA approach is to provide an active and healthy life to rhinitis sufferers, whatever their age, sex or socio-economic status, in order to reduce health and social inequalities incurred by the disease.