A next-generation sequencing approach to identify gene mutations in early-and late-onset hypertrophic cardiomyopathy patients of an Italian cohort

Sequencing of sarcomere protein genes in patients fulfilling the clinical diagnostic criteria for hypertrophic cardiomyopathy (HCM) identifies a disease-causing mutation in 35% to 60% of cases. Age at diagnosis and family history may increase the yield of mutations screening. In order to assess whether Next-Generation Sequencing (NGS) may fulfil the molecular diagnostic needs in HCM, we included 17 HCM-related genes in a sequencing panel run on PGM IonTorrent. We selected 70 HCM patients, 35 with early (≤25 years) and 35 with late (≥65 years) diagnosis of disease onset. All samples had a 98.6% average of target regions, with coverage higher than 20× (mean coverage 620×). We identified 41 different mutations (seven of them novel) in nine genes: MYBPC3 (17/41 = 41%); MYH7 (10/41 = 24%); TNNT2, CAV3 and MYH6 (3/41 = 7.5% each); TNNI3 (2/41 = 5%); GLA, MYL2, and MYL3 (1/41=2.5% each). Mutation detection rate was 30/35 (85.7%) in early-onset and 8/35 (22.9%) in late-onset HCM patients, respectively (p < 0.0001). The overall detection rate for patients with positive family history was 84%, and 90.5% in patients with early disease onset. In our study NGS revealed higher mutations yield in patients with early onset and with a family history of HCM. Appropriate patient selection can increase the yield of genetic testing and make diagnostic testing cost-effective

Strain-Induced Plasmon Confinement in Polycrystalline Graphene

Terahertz spectroscopy is a perfect tool to investigate the electronic intraband conductivity of graphene, but a phenom-enological model (Drude-Smith) is often needed to describe disorder. By studying the THz response of isotropically strained polycrystalline graphene and using a fully atomistic computational approach to fit the results, we demonstrate here the connection between the Drude-Smith parameters and the microscopic behavior. Importantly, we clearly show that the strain-induced changes in the conductivity originate mainly from the increased separation between the single-crystal grains, leading to enchanced localization of the plasmon excitations. Only at the lowest strain values explored, a behavior consistent with the deformation of the individual grains can instead be observed

Young people's media use and adherence to preventive measures in the “infodemic” : is it masked by political ideology?

Background: Navigating in the COVID-19 “infodemic” and adhering to preventive measures is especially challenging for young people. The use of information sources and political ideology are empirically important factors for adherence behavior. How these two are interconnected and if political ideology on its own contributes to adherence is not yet well established in young people. Objective: This study investigates what role political ideology and political extremism, use of information sources, trust and risk perception play for adhering to preventive measures in young people. Methods: Cross-sectional online survey in a representative random sample of young people aged 15–34 in two German-speaking and one Italian-speaking canton of Switzerland. The hypotheses were tested with logistic regression and multivariate regression analysis. Results: The odds for using the following information sources decreases for young people positioning themselves towards the right pole of the ideology scale: health-based sources 0.90 (CI: 0.84–0.97), news sources 0.93 (CI 0.87–0.997) and other websites 0.83 (CI: 0.75–0.92). In contrast, the odds of using broadcasting sources increases for young people positioning themselves towards the right pole of the ideology scale (OR: 1.08, CI 1.01–1.15). The odds of using social media decreases with higher political extremism (OR 0.88, CI 0.78–0.99). Political extremism was related with lower adherence to preventive measures in young people with low trust in the government, scientists, and journalists. Conclusion: Young peoples' use of information sources is associated with their political ideology and political extremism needs to be taken in account in conjunction with low trust

A Novel Nonsense Pathogenic TTN Variant Identified in a Patient with Severe Dilated Cardiomyopathy

Both genetic and environmental factors contribute to the development of dilated cardiomyopathy. Among the genes involved, TTN mutations, including truncated variants, explain 25% of DCM cases. We performed genetic counseling and analysis on a 57-year-old woman diagnosed with severe DCM and presenting relevant acquired risk factors for DCM (hypertension, diabetes, smoking habit, and/or previous alcohol and cocaine abuse) and with a family history of both DCM and sudden cardiac death. The left ventricular systolic function, as assessed by standard echocardiography, was 20%. The genetic analysis performed using TruSight Cardio panel, including 174 genes related to cardiac genetic diseases, revealed a novel nonsense TTN variant (TTN:c.103591A &gt; T, p.Lys34531*), falling within the M-band region of the titin protein. This region is known for its important role in maintaining the structure of the sarcomere and in promoting sarcomerogenesis. The identified variant was classified as likely pathogenic based on ACMG criteria. The current results support the need of genetic analysis in the presence of a family history, even when relevant acquired risk factors for DCM may have contributed to the severity of the disease

Long QTc in hypertrophic cardiomyopathy. A consequence of structural myocardial damage or a distinct genetic disease?

Hypertrophic cardiomyopathy (HCM) is an autosomal dominant disease, characterized by the presence of unexplained left ventricular hypertrophy. This condition is often associated with electrocardiographic abnormalities including QTc prolongation occurring in 13% of patients. The main explanation for prolonged QTc in HCM is myocardial hypertrophy and the related structural damage. However, other mechanisms, including long QT syndrome (LQTS) genes mutations, may be involved. In the present study we explored the hypothesis of a distinct genetic basis underlying QTc prolongation in HCM by investigating the potential co-inheritance of pathogenic gene variants associated with LQTS and HCM. For this purpose, starting from a cohort of 150 HCM patients carrying pathogenic variants in sarcomere genes, we selected 25 patients carrying a QTc prolongation unexplained by any other cause. The QTc was considered prolonged if greater than 450 ms in males and greater than 470 ms in females. The NGS analysis was performed with Illumina TrueSight Cardio panel genes on Illumina MiniSeq platform. We identified pathogenic/likely pathogenic variants in the KCNQ1 in two patients (c.1781G &gt; A, p. Arg594Gln; c.532G &gt; A, p. Ala178Thr) (8%). Variants of uncertain significance were identified in SCN5A, KCNJ5, AKAP9 and ANK2 in four patients (16%). Although the results are limited by the small number of patients included in the study, they highlight a minor contribution of LQTS genes for QTc prolongation in HCM patients. The screening for ion channel genes mutations may be considered in HCM patients with prolonged QTc unexplained by any other cause. This in-depth molecular diagnosis may contribute to improve risk stratification and treatment planning

Risk stratification in hypertrophic cardiomyopathy. Insights from genetic analysis and cardiopulmonary exercise testing

The role of genetic testing over the clinical and functional variables, including data from the cardiopulmonary exercise test (CPET), in the hypertrophic cardiomyopathy (HCM) risk stratification remains unclear. A retrospective genotype–phenotype correlation was performed to analyze possible differences between patients with and without likely pathogenic/pathogenic (LP/P) variants. A total of 371 HCM patients were screened at least for the main sarcomeric genes MYBPC3 (myosin binding protein C), MYH7 (β-myosin heavy chain), TNNI3 (cardiac troponin I) and TNNT2 (cardiac troponin T): 203 patients had at least an LP/P variant, 23 patients had a unique variant of uncertain significance (VUS) and 145 did not show any LP/P variant or VUS. During a median 5.4 years follow-up, 51 and 14 patients developed heart failure (HF) and sudden cardiac death (SCD) or SCD-equivalents events, respectively. The LP/P variant was associated with a more aggressive HCM phenotype. However, left atrial diameter (LAd), circulatory power (peak oxygen uptake*peak systolic blood pressure, CP%) and ventilatory efficiency (C-index = 0.839) were the only independent predictors of HF whereas only LAd and CP% were predictors of the SCD end-point (C-index = 0.738). The present study reaffirms the pivotal role of the clinical variables and, particularly of those CPET-derived, in the HCM risk stratification.publishedVersio

COVIDisc – a focus on vector populations

The containment of the pandemic relies heavily on the communication between public health organizations and individual social groups. Therefore, public discourses and discursive practices of specific audiences play a crucial role in the policy implementation during a pandemic. The aim of the project is to gain an understanding of the public discourse and its perception by young people in Switzerland and, based on this, to formulate communication recommendations for public health organizations. In addition, a strategy for crisis communication as well as audience and message design will be developed for the current COVID 19 pandemic and for future public health measures

Beyond BRCA1 and BRCA2: deleterious variants in DNA repair pathway genes in italian families with breast/ovarian and pancreatic cancers

The 5-10% of breast/ovarian cancers (BC and OC) are inherited, and germline pathogenic (P) variants in DNA damage repair (DDR) genes BRCA1 and BRCA2 explain only 10-20% of these cases. Currently, new DDR genes have been related to BC/OC and to pancreatic (PC) cancers, but the prevalence of P variants remains to be explored. The purpose of this study was to investigate the spectrum and the prevalence of pathogenic variants in DDR pathway genes other than BRCA1/2 and to correlate the genotype with the clinical phenotype. A cohort of 113 non-BRCA patients was analyzed by next-generation sequencing using a multigene panel of the 25 DDR pathways genes related to BC, OC, and PC. We found 43 unique variants in 18 of 25 analyzed genes, 14 classified as P/likely pathogenic (LP) and 28 as variants of uncertain significance (VUS). Deleterious variants were identified in 14% of index cases, whereas a VUS was identified in 20% of the probands. We observed a high incidence of deleterious variants in the CHEK2 gene, and a new pathogenic variant was detected in the RECQL gene. These results supported the clinical utility of multigene panel to increase the detection of P/LP carriers and to identify new actionable pathogenic gene variants useful for preventive and therapeutic approaches

Sim Handbook - A practical guide for applying Social Marketing in the disability sector

This handbook is one of the outputs of the SIM project, funded by the European Erasmus+ Programme (grant ID 2019-1-PT01-KA204-060716), which tackles the need to improve the social inclusion of disadvantaged groups, specifically those with disabilities. The handbook can be used as guided course curriculum or as a self-study book. The handbook will contribute to social sector to integrate a methodology very useful to tackle problems from a practical perspective. THE HANDBOOK IS DESIGNED FOR: • Social educators in charge of improving the competences of disadvantaged groups (midstream level) and their supervisors (strategic level). In other words, people working in social inclusion about social inclusion programmes as well as front line professionals. • University Professors who integrate it into their curricula of marketing, health, and social marketing studies. THE HANDBOOK IS AIMED TO BENEFIT: • Midstream level professionals: social educators such as social workers, psychologists, occupational therapists and employment mediators which directly work improving the competences of people with disabilities. The relationships developed in the disability sector between front-line professionals and customers are unique, genuine and long-lasting; and • Upstream level professionals: decision takers, managers of organizations, training program developers who supervise the tasks of educators, providing the training needed organizational resources. THE HANDBOOK WILL IMPROVE THE COMPETENCES OF SOCIAL EDUCATORS AND COORDINATORS TO: a) social marketing techniques and strategies; b) the English language; c) dealing with social inclusion problems from a different perspective; d) critical thinking; e) searching for and making use of relevant, trustworthy information2019-1-PT01-KA204-06071

Pedagogical strategy. Social marketing for social inclusion: case studies

The Social Inclusion Marketing (SIM) Project, which is financed by the Erasmus+ Programme, is the outcome of a concerted 3-year effort between partners and specialists who have developed specialized training on social marketing strategies to put into practice in social organizations. In sum, the motto is Social Marketing for Social Inclusion. It builds on the experience and expertise of four partner organizations – two universities and two nonprofit institutions working with people with disabilities. Their approach is based on practical training and study cases learning, action research and inter-disciplinary thinking. The project was designed to integrate the theoretical framework of social marketing and social inclusion fields to provide better services and quality of life of people with disabilities and their families. It focuses on looking through the needs of disability professionals when faced with a problem and finding solutions under the social marketing lens.2019-1-PT01-KA204-06071