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Mutations in the LMNA gene are associated with a wide spectrum of disease phenotypes, ranging from neuromuscular, cardiac and metabolic disorders to premature aging syndromes. Skeletal muscle involvement may present with different phenotypes: limb-girdle muscular dystrophy type 1B or LMNA-related dystrophy; autosomal dominant Emery-Dreifuss muscular dystrophy; and a congenital form of muscular dystrophy, frequently associated with early onset of arrhythmias. Heart involvement may occur as part of the muscle involvement or independently, regardless of the presence of the myopathy. Notably conduction defects and dilated cardiomyopathy may exist without a muscle disease. This paper will focus on cardiac diseases presenting as the first manifestation of skeletal muscle hereditary disorders such as laminopathies, inspired by two large families with cardiovascular problems long followed by conventional cardiologists who did not suspect a genetic muscle disorder underlying these events. Furthermore it underlines the need for a multidisciplinary approach in these disorders and how the figure of the cardio-myo-geneticist may play a key role in facilitating the diagnostic process, and addressing the adoption of appropriate prevention measures.

Cardiomyopathy associated with dystrophinopathies - Duchenne muscular Dystrophy (DMD), Becker muscular dystrophy (BMD), X-linked dilated cardiomyopathy (XL-CM) and cardiomyopathy of Duchenne/Becker (DMD/BMD carriers - is an almost constant manifestation of these neuromuscular disorders and contribute significantly to their morbidity and mortality. Dystrophinopathic cardiomyopathy is the result of the dystrophin protein deficiency at the myocardium level, parallel to that occurring at the skeletal muscle level. Typically, cardiomyopathy begins as a "presymptomatic" stage in the first decade of life and evolves in a stepwise manner toward an end-stage dilated cardiomyopathy. Nearly complete replacement of the myocardium by fibrous and fatty connective tissue results in an irreversible cardiac failure, characterized by a further reduction of ejection fraction (EF < 30%) and frequent episodes of acute heart failure (HF). The picture of a severe dilated cardiomyopathy with intractable heart failure is typical of dystrophinopathies. Despite an appropriate pharmacological treatment, this condition is irreversible because of the extensive loss of myocites. Heart transplantation is the only curative therapy for patients with end-stage heart failure, who remain symptomatic despite an optimal medical therapy. However there is a reluctance to perform heart transplantation (HT) in these patients due to the scarcity of donors and the concerns that the accompanying myopathy will limit the benefits obtained through this therapeutic option. Therefore the only possibility to ameliorate clinical symptoms, prevent fatal arrhythmias and cardiac death in dystrophinopathic patients could be the implantation of intracardiac device (ICD) or resynchronizing devices with defibrillator (CRT-D). This overview reports the personal series of patients affected by DMD and BMD and DMD carriers who received ICD or CRT-D system, describe the clinical outcomes so far published and discuss pro and cons in the use of such devices.

Aim: The aim of this study was to test the mediating role of the satisfaction of dental students’ basic psychological needs of autonomy, competence and relatedness on the association between learning climate, feedback and student motivation. The latter was based on the self- determination theory’s concepts of differentiation of autonomous motivation, controlled motivation and amotivation.Methods: A cross- sectional correlational study was conducted where 924 students completed self- reported questionnaires measuring motivation, perception of the learning climate, feedback and basic psychological needs satisfaction. Descriptive sta-tistics, Cronbach’s alpha scores and bivariate correlations were computed. Mediation of basic needs on each predictor- outcome association was tested based on a series of regression analyses. Finally, all variables were integrated into one structural equation model, controlling for the effects of age, gender and year of study.Results: Cronbach’s alpha scores were acceptable (.655 to .905). Correlation analyses showed positive and significant associations between both an autonomy- supportive learning climate and the quantity and quality of feedback received, and students’ au-tonomous motivation, which decreased and became negative when correlated with controlled motivation and amotivation, respectively. Regression analyses revealed that these associations were indirect and mediated by how these predictors satisfied students’ basic psychological needs. These results were corroborated by the structural equation analysis, in which data fit the model well and regression paths were in the expected direction.Conclusion: An autonomy- supportive learning climate and the quantity and quality of feedback were positive predictors of students’ autonomous motivation and negative predictors of amotivation. However, this was an indirect association mediated by the satisfaction of students’ basic psychological needs. Consequently, supporting stu-dents’ needs of autonomy, competence and relatedness might lead to optimal types of motivation, which has an important influence on dental education.

As the Internet autonomous sytem (AS)-level topology grows over time, some of its structural properties remain unchanged. Such time-invariant properties are generally interesting because they tend to reflect some fundamental processes or constraints behind Internet growth. As has been shown before, the time-invariant structural properties of the Internet include some most basic ones, such as the degree distribution or clustering. Here, we add to this time-invariant list a nontrivial property- k -dense decomposition. This property is derived from a recursive form of edge multiplicity, defined as the number of triangles that share a given edge. We show that after proper normalization, the k-dense decomposition of the Internet has remained stable over the last decade, even though the Internet size has approximately doubled, and so has the k -density of its k -densest core. This core consists mostly of content providers peering at Internet eXchange Points, and it only loosely overlaps with the high-degree or high-rank AS core, consisting mostly of tier-1 transit providers. We thus show that high degrees and high k -densities reflect two different Internet-specific properties of ASs (transit versus content providers). As a consequence, even though degrees and k-densities of nodes are correlated, the relative fluctuations are strong, and related to that, random graphs with the same degree distribution or even degree correlations as in the Internet, do not reproduce its k-dense decomposition. Therefore an interesting open question is what Internet topology models or generators can fully explain or at least reproduce the k -dense properties of the Internet.

We examine the impact of new medical information on drug safety on preventive health behavior. We exploit the release of the findings of the Women's Health Initiative Study (WHIS) -the largest randomized controlled trial of women's health- which demonstrated in 2002 that long-term Hormone Replacement Therapy increases the risk of heart attacks, stroke, blood clots and breast cancer among healthy postmenopausal women. Because hormone replacement is a therapy exclusive to women, we estimate the spillover effects of the WHIS findings on health behavior by means of a difference-in-differences methodology using men of similar ages as the control group. Using data from the Behavioral Risk Factor Surveillance System for 1998-2007, we find statistically significant small negative spillovers on post-menopausal women's likelihood of having an annual checkup and choice of a healthy diet, as proxied by daily fruit consumption. Our results also indicate that the observed spillover effects of drug safety on health behavior were entirely driven by the less educated. These findings suggest that policies aimed at raising awareness on the safety of medications may have unintended spillover effects on health behavior and that these spillovers may contribute to the existing health disparities by education.

In an aging society, determining which factors contribute to the employment of older individuals is increasingly important. This paper sheds light on the impact of medical innovation in the form of Hormone Replacement Therapy (HRT) on employment of middle-aged women. HRT are drugs taken by middle-aged women to soften symptoms related to menopause. Before 2002, HRT products were among the most popular prescription drugs in America. We use the timing of the release of information of the potential hazardous effects of HRT—uncovered in 2002 by the largest randomized trials on women ever undertaken—as an instrument for the purchase of the affected drugs within a Fixed Effect Instrumental Variable framework. We find that HRT use impacts employment: namely, that HRT use increases employment by 25 percentage points among middle-aged women who would have taken HRT but who do not take HRT after the release of information of its potential hazardous effects.