Search

AIMS: Atrial fibrillation (AF) is the most common type of cardiac arrhythmias, whose incidence is likely to increase with the aging of the population. It is considered a progressive condition, frequently observed as a complication of other cardiovascular disorders. However, recent genetic studies revealed the presence of several mutations and variants linked to AF, findings that define AF as a multifactorial disease. Due to the complex genetics and paucity of models, molecular mechanisms underlying the initiation of AF are still poorly understood. Here we investigate the pathophysiological mechanisms of a familial form of AF, with particular attention to the identification of putative triggering cellular mechanisms, using patient's derived cardiomyocytes (CMs) differentiated from induced pluripotent stem cells (iPSCs). METHODS AND RESULTS: Here we report the clinical case of three siblings with untreatable persistent AF whose whole-exome sequence analysis revealed several mutated genes. To understand the pathophysiology of this multifactorial form of AF we generated three iPSC clones from two of these patients and differentiated these cells towards the cardiac lineage. Electrophysiological characterization of patient-derived CMs (AF-CMs) revealed that they have higher beating rates compared to control (CTRL)-CMs. The analysis showed an increased contribution of the If and ICaL currents. No differences were observed in the repolarizing current IKr and in the sarcoplasmic reticulum calcium handling. Paced AF-CMs presented significantly prolonged action potentials and, under stressful conditions, generated both delayed after-depolarizations of bigger amplitude and more ectopic beats than CTRL cells. CONCLUSIONS: Our results demonstrate that the common genetic background of the patients induces functional alterations of If and ICaL currents leading to a cardiac substrate more prone to develop arrhythmias under demanding conditions. To our knowledge this is the first rep

Purpose: The purpose of this paper is to propose a systematic review of the contributions present in the literature about walkability. This is aimed at defining a set of criteria and methodologies for the assessment of the level of pedestrian friendliness of cities characterised by mass tourism. Design/methodology/approach: The paper is based on a theoretical review about walkability and on the study of mass tourism phenomenon in Venice in relation to the ongoing de-urbanisation process. The analysis of open data sets provides by the Public Institutions of Venice and the execution of on-site observations allowed a qualitative assessment on the level of walkability of the historical centre of Venice. Findings: The results of the proposed study highlighted that the level of walkability in Venice is profoundly affected by the lack of base services, the presence of massive tourism flows and the scarcity of road signage. Practical implications: All the elements highlighted in this work could lead to proposing several design solutions and policies to manage the tourism phenomenon in Venice in a more effective and sustainable manner. Social implications: The assessment and enhancement of the level of walkability of urban areas represent a useful tool to manage the tourist flows and to reduce the conflicts between inhabitants and visitors in tourism cities. Originality/value: The current work represents a valuable contribution towards the systematisation of the theoretical and methodological framework towards a tourism-based walkability assessment