Inherited Arrhythmogenic Diseases

Twelve years after the identification of the molecular bases of the long-QT syndrome, it is now possible to express some considerations on the impact that genetic findings have had in the understanding of inherited arrhythmogenic diseases. Along with the excitement for the emerging data on genotype/phenotype correlation and for the development of the first recommendations for gene-specific management of patients, it is also important to acknowledge the unexpected complexity that has emerged. The focus of this article is to analyze the elusive aspects of the relationship between genetic defects and clinical manifestations and to propose some research directions that may provide the needed answers to move forward in the understanding of the genetics of heart rhythm abnormalities

Sleep quality in patients with primary Sjögren's syndrome

Objective To assess the sleep quality in primary Sjögren’s syndrome (pSS) patients and evaluate its relationship with the disease, quality of life and mood disorders. Methods The sleep quality of 29 pSS women and 29 matched controls was assessed by the Pittsburgh Sleep Quality Index (PSQI). Seven domains are grouped according to three factors: F1 perceived sleep quality (subjective sleep quality, sleep latency, use of sleeping medication), F2 sleep efficiency (sleep duration, habitual sleep efficiency) and F3 daily disturbances (sleep disturbances, daytime dysfunction). These domains are scored as a single factor of global sleep quality. The Short Form Health Survey (SF-36), Functional Assessment of Chronic Illness Therapy (FACIT) fatigue scale and Hospital Anxiety and Depression Scale (HADS) were also administered. Disease activity and damage were evaluated with the EULAR Sjögren’s syndrome disease activity index (ESSDAI), the Sjögren’s Syndrome Disease Activity and Damage Indexes (SSDAI, SSDDI). Results The mean PSQI global score had higher pathological values (8.6±4.6) compared with controls (5.6±2.2) (p=0.002). F1 and F3 were significantly worse in cases (p=0.01, p=0.009). A negative correlation was found between SF-36 subscales and the global PSQI, F2 and F3. The anxiety HADS correlated with F2 and F3, while depression only with F3. No correlation with FACIT and disease indexes emerged. Conclusion Using PSQI, an impaired sleep quality was demonstrated in pSS patients, especially with perceived quality and the daily disturbances. It is associated with a reduced quality of life but not with disease-related variables.Objective To assess the sleep quality in primary Sjögren’s syndrome (pSS) patients and evaluate its relationship with the disease, quality of life and mood disorders. Methods The sleep quality of 29 pSS women and 29 matched controls was assessed by the Pittsburgh Sleep Quality Index (PSQI). Seven domains are grouped according to three factors: F1 perceived sleep quality (subjective sleep quality, sleep latency, use of sleeping medication), F2 sleep efficiency (sleep duration, habitual sleep efficiency) and F3 daily disturbances (sleep disturbances, daytime dysfunction). These domains are scored as a single factor of global sleep quality. The Short Form Health Survey (SF-36), Functional Assessment of Chronic Illness Therapy (FACIT) fatigue scale and Hospital Anxiety and Depression Scale (HADS) were also administered. Disease activity and damage were evaluated with the EULAR Sjögren’s syndrome disease activity index (ESSDAI), the Sjögren’s Syndrome Disease Activity and Damage Indexes (SSDAI, SSDDI). Results The mean PSQI global score had higher pathological values (8.6±4.6) compared with controls (5.6±2.2) (p=0.002). F1 and F3 were significantly worse in cases (p=0.01, p=0.009). A negative correlation was found between SF-36 subscales and the global PSQI, F2 and F3. The anxiety HADS correlated with F2 and F3, while depression only with F3. No correlation with FACIT and disease indexes emerged. Conclusion Using PSQI, an impaired sleep quality was demonstrated in pSS patients, especially with perceived quality and the daily disturbances. It is associated with a reduced quality of life but not with disease-related variables

Role of Genetic Analyses in Cardiology

Genetic analysis can be performed to identify the molecular substrate of inherited arrhythmogenic diseases; however, the role of this information in helping the management of patients is still debated. Here, we support the view that the practical value of genetic analysis is different in the various inherited conditions and that it is strongly influenced by the amount of information available in each disease about genotype-phenotype correlations. In some diseases, clinical management of patients is profoundly affected by the type of the underlying genetic defect; therefore, in these conditions, there is a high priority to introduce genetic analysis into clinical practice. In the absence of genotype-phenotype correlations, genetic testing still can be very useful when there is a clinical advantage in establishing presymptomatic diagnosis or when screening of family members may point to reproductive counseling. Finally, there is a high priority for introducing genetic testing for those genetic diseases in which a limited number of genes allow a high yield of successfully genotyped patients. We have developed a "score" to compare the value of genetic testing in arrhythmogenic diseases and to convey our view that the clinical role of genetic analysis is different in the various inherited cardiomyopathies and channelopathies. Healthcare authorities should become responsive to the advancement of knowledge in this field and should help facilitate access to genotyping for families affected by those conditions in which genetic analysis provides useful information for clinical management

Brugada syndrome

A novel clinical entity characterized by ST segment elevation in right precordial leads (V1 to V3), incomplete or complete right bundle branch block, and susceptibility to ventricular tachyarrhythmia and sudden cardiac death has been described by Brugada et al. in 1992. This disease is now frequently called "Brugada syndrome" (BrS). The prevalence of BrS in the general population is unknown. The suggested prevalence ranges from 5/1,000 (Caucasians) to 14/1,000 (Japanese). Syncope, typically occurring at rest or during sleep (in individuals in their third or fourth decades of life) is a common presentation of BrS. In some cases, tachycardia does not terminate spontaneously and it may degenerate into ventricular fibrillation and lead to sudden death. Both sporadic and familial cases have been reported and pedigree analysis suggests an autosomal dominant pattern of inheritance. In approximately 20% of the cases BrS is caused by mutations in the SCN5A gene on chromosome 3p21-23, encoding the cardiac sodium channel, a protein involved in the control of myocardial excitability. Since the use of the implantable cardioverter defibrillator (ICD) is the only therapeutic option of proven efficacy for primary and secondary prophylaxis of cardiac arrest, the identification of high-risk subjects is one of the major goals in the clinical decision-making process. Quinidine may be regarded as an adjunctive therapy for patients at higher risk and may reduce the number of cases of ICD shock in patients with multiple recurrences

The long QT syndrome

Major progress has taken place, and at a very rapid pace, in the understanding of the congenital long QT syndrome (LQTS). This has been the direct consequence of the identification of several of the genes responsible for LQTS and of the studies that have followed, at both basic and clinical levels. A key issue is represented by the fact that all LQTS genes identified so far encode for ionic channels involved in the control of repolarization. The expression studies of the mutated genes have allowed identification of the specific electrophysiologic consequences of the specific mutations and have demonstrated alterations in the NA+ and in K+ currents sufficient to explain the prolongation of action potential duration and, hence, of the QT interval. Ongoing studies in the selected LQTS patients, for whom the specific mutations are known, are allowing a unique understanding of the complex genotype-phenotype correlation. These studies indicate the existence of what appear to be gene-specific patterns in many clinically important features such as the response to therapeutic interventions, the response to increases in heart rate, and in the factors that precipitate the life-threatening arrhythmias typical of this intriguing disease

NEMATODE COOMUNITIES AS INDICATORS OF SOIL QUALITY IN VINEYARD SYSTEM: A CASE OF STUDY IN DEGRADED AREAS

The restoring effect of selective agronomic strategies on optimal soil functionality of degraded areas within organic vineyard was evaluated using the nematode community as an indicator of soil quality. Three different restoring strategies were implemented in two organic farms located in Tuscany (Italy). The relative abundance of nematode trophic groups and the maturity index showed that the use of compost improved soil biological quality and increased the abundance of predators. Instead, dry mulching and green manure applications were useful to control the most dangerous nematodes of grapevines, namely the virus-vector Xiphinema index (Longidoridae)

The Structural–Functional Crosstalk of the Calsequestrin System: Insights and Pathological Implications

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MAPPING SOIL SPATIAL VARIABILITY AT HIGH DETAIL BY PROXIMAL SENSORS FOR A VINEYARD PLANNING

Planning new vineyard needs accurate information about soil features and their spatial variability. The use of soil proximal sensors, coupled by few detailed soil observations and analysis allows to obtain high detailed maps of soil variability at affordable costs. The work showed the methodology to interpolate the proximal sensors data and to delineate homogeneous area by clustering, corresponding to likely soil units. The description and analysis of one profile for each homogeneous area allowed to describe the soil features of each soil typological units and to produce useful thematic maps for vineyard planning

Role of the JP45-Calsequestrin Complex on Calcium Entry in Slow Twitch Skeletal Muscles

We exploited a variety of mouse models to assess the roles of JP45-CASQ1 (CASQ, calsequestrin) and JP45-CASQ2 on calcium entry in slow twitch muscles. In flexor digitorum brevis (FDB) fibers isolated from JP45-CASQ1-CASQ2 triple KO mice, calcium transients induced by tetanic stimulation rely on calcium entry via La3+- and nifedipine-sensitive calcium channels. The comparison of excitation-coupled calcium entry (ECCE) between FDB fibers from WT, JP45KO, CASQ1KO, CASQ2KO, JP45-CASQ1 double KO, JP45-CASQ2 double KO, and JP45-CASQ1-CASQ2 triple KO shows that ECCE enhancement requires ablation of both CASQs and JP45. Calcium entry activated by ablation of both JP45-CASQ1 and JP45-CASQ2 complexes supports tetanic force development in slow twitch soleus muscles. In addition, we show that CASQs interact with JP45 at Ca2+ concentrations similar to those present in the lumen of the sarcoplasmic reticulum at rest, whereas Ca2+ concentrations similar to those present in the SR lumen after depolarization-induced calcium release cause the dissociation of JP45 from CASQs. Our results show that the complex JP45-CASQs is a negative regulator of ECCE and that tetanic force development in slow twitch muscles is supported by the dynamic interaction between JP45 and CASQs