97 research outputs found
Is arrhythmogenic right ventricular cardiomyopathy a paediatric problem too?
Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a heart muscle disease
that is often familial, characterized by arrhythmias of right ventricular origin, due to
transmural fatty or fibrofatty replacement of atrophic myocardium. ARVC is usually
diagnosed in the clinical setting between 20 and 40 years of age. The disease is
seldom recognised in infancy or under the age of 10, probably because the clinical
expression of the disease is normally postponed to youth and adulthood. This review
focuses its attention to the pediatric age, defined as the period of life raging from birth
to 18 years. During this span of life, ARVC is not so rare as previously supposed and
can be identified by applying the same diagnostic criteria proposed for the adult.
Ventricular arrhythmias range from isolated ventricular arrhythmias to sustained
ventricular tachycardia and fibrillation. Children and adolescents with ARVC must be
carefully evaluated and followed-up especially when a family positive history is
present, taking into account the high probability during this life-period that
asymptomatic affected patients become symptomatic or that arrhythmias worsen
during follow-up. The recent identification of the first defective gene opens new
avenues for the early identification of affected subjects even when asymptomatic.peer-reviewe
Migration routes and non-breeding areas of Common Terns (Sterna hirundo) from the Azores
We describe the migration routes and non-breeding areas of Common Terns (Sterna hirundo) from the Azores Archipelago, based on ringing (banding) recoveries and tracking of three birds using geolocators. Over 20 years, there have been 55 transatlantic recoveries of Common Terns from the Azores population: six from Argentina and 49 from Brazil. The three tracked birds migrated south in different months (August, September, November), but the northern migration was more synchronous, with all leaving in April. The birds were tracked to three areas of the South American coast: the male spent November–April on the northern Brazilian coast (13°N–2°S), whereas the two females first spent some time off central-eastern Brazil (4–16°S; one for 1 week, the other for 3 months) and then moved south to the coast of south-eastern Brazil, Uruguay and northern Argentina (24–39°S). Although caution is needed given the small sample size and errors associated with geolocation, the three tracked terns potentially travelled a total of ~23 200 km to and returning from their non-breeding areas, representing an average movement of ~500 km day–1. With the exception of Belém, in northern Brazil, and Lagoa do Peixe, in southern Brazil, the coastal areas used by the tracked birds were also those with concentrations of ringing recoveries, confirming their importance as non-breeding areas for birds from the Azores
Missense mutations in Desmocollin-2 N-terminus, associated with arrhythmogenic right ventricular cardiomyopathy, affect intracellular localization of desmocollin-2 in vitro
<p>Abstract</p> <p>Background</p> <p>Mutations in genes encoding desmosomal proteins have been reported to cause arrhythmogenic right ventricular cardiomyopathy (ARVC), an autosomal dominant disease characterised by progressive myocardial atrophy with fibro-fatty replacement.</p> <p>We screened 54 ARVC probands for mutations in desmocollin-2 (<it>DSC2</it>), the only desmocollin isoform expressed in cardiac tissue.</p> <p>Methods</p> <p>Mutation screening was performed by denaturing high-performance liquid chromatography and direct sequencing.</p> <p>To evaluate the pathogenic potentials of the <it>DSC2 </it>mutations detected in patients affected with ARVC, full-length wild-type and mutated cDNAs were cloned in eukaryotic expression vectors to obtain a fusion protein with green fluorescence protein (GFP); constructs were transfected in neonatal rat cardiomyocytes and in HL-1 cells.</p> <p>Results</p> <p>We identified two heterozygous mutations (c.304G>A (p.E102K) and c.1034T>C (p.I345T)) in two probands and in four family members. The two mutations p.E102K and p.I345T map to the N-terminal region, relevant to adhesive interactions.</p> <p>In vitro functional studies demonstrated that, unlike wild-type DSC2, the two N-terminal mutants are predominantly localised in the cytoplasm.</p> <p>Conclusion</p> <p>The two missense mutations in the N-terminal domain affect the normal localisation of DSC2, thus suggesting the potential pathogenic effect of the reported mutations. Identification of additional DSC2 mutations associated with ARVC may result in increased diagnostic accuracy with implications for genetic counseling.</p
Arrhythmogenic right ventricular cardiomyopathy/dysplasia
Arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D) is a heart muscle disease clinically characterized by life-threatening ventricular arrhythmias. Its prevalence has been estimated to vary from 1:2,500 to 1:5,000. ARVC/D is a major cause of sudden death in the young and athletes. The pathology consists of a genetically determined dystrophy of the right ventricular myocardium with fibro-fatty replacement to such an extent that it leads to right ventricular aneurysms. The clinical picture may include: a subclinical phase without symptoms and with ventricular fibrillation being the first presentation; an electrical disorder with palpitations and syncope, due to tachyarrhythmias of right ventricular origin; right ventricular or biventricular pump failure, so severe as to require transplantation. The causative genes encode proteins of mechanical cell junctions (plakoglobin, plakophilin, desmoglein, desmocollin, desmoplakin) and account for intercalated disk remodeling. Familiar occurrence with an autosomal dominant pattern of inheritance and variable penetrance has been proven. Recessive variants associated with palmoplantar keratoderma and woolly hair have been also reported. Clinical diagnosis may be achieved by demonstrating functional and structural alterations of the right ventricle, depolarization and repolarization abnormalities, arrhythmias with the left bundle branch block morphology and fibro-fatty replacement through endomyocardial biopsy. Two dimensional echo, angiography and magnetic resonance are the imaging tools for visualizing structural-functional abnormalities. Electroanatomic mapping is able to detect areas of low voltage corresponding to myocardial atrophy with fibro-fatty replacement. The main differential diagnoses are idiopathic right ventricular outflow tract tachycardia, myocarditis, dialted cardiomyopathy and sarcoidosis. Only palliative therapy is available and consists of antiarrhythmic drugs, catheter ablation and implantable cardioverter defibrillator. Young age, family history of juvenile sudden death, QRS dispersion ≥ 40 ms, T-wave inversion, left ventricular involvement, ventricular tachycardia, syncope and previous cardiac arrest are the major risk factors for adverse prognosis. Preparticipation screening for sport eligibility has been proven to be effective in detecting asymptomatic patients and sport disqualification has been life-saving, substantially declining sudden death in young athletes
Myocyte necrosis underlies progressive myocardial dystrophy in mouse dsg2-related arrhythmogenic right ventricular cardiomyopathy
Joint Observation of the Galactic Center with MAGIC and CTA-LST-1
MAGIC is a system of two Imaging Atmospheric Cherenkov Telescopes (IACTs), designed to detect very-high-energy gamma rays, and is operating in stereoscopic mode since 2009 at the Observatorio del Roque de Los Muchachos in La Palma, Spain. In 2018, the prototype IACT of the Large-Sized Telescope (LST-1) for the Cherenkov Telescope Array, a next-generation ground-based gamma-ray observatory, was inaugurated at the same site, at a distance of approximately 100 meters from the MAGIC telescopes. Using joint observations between MAGIC and LST-1, we developed a dedicated analysis pipeline and established the threefold telescope system via software, achieving the highest sensitivity in the northern hemisphere. Based on this enhanced performance, MAGIC and LST-1 have been jointly and regularly observing the Galactic Center, a region of paramount importance and complexity for IACTs. In particular, the gamma-ray emission from the dynamical center of the Milky Way is under debate. Although previous measurements suggested that a supermassive black hole Sagittarius A* plays a primary role, its radiation mechanism remains unclear, mainly due to limited angular resolution and sensitivity. The enhanced sensitivity in our novel approach is thus expected to provide new insights into the question. We here present the current status of the data analysis for the Galactic Center joint MAGIC and LST-1 observations
Global disparities in surgeons’ workloads, academic engagement and rest periods: the on-calL shIft fOr geNEral SurgeonS (LIONESS) study
: The workload of general surgeons is multifaceted, encompassing not only surgical procedures but also a myriad of other responsibilities. From April to May 2023, we conducted a CHERRIES-compliant internet-based survey analyzing clinical practice, academic engagement, and post-on-call rest. The questionnaire featured six sections with 35 questions. Statistical analysis used Chi-square tests, ANOVA, and logistic regression (SPSS® v. 28). The survey received a total of 1.046 responses (65.4%). Over 78.0% of responders came from Europe, 65.1% came from a general surgery unit; 92.8% of European and 87.5% of North American respondents were involved in research, compared to 71.7% in Africa. Europe led in publishing research studies (6.6 ± 8.6 yearly). Teaching involvement was high in North America (100%) and Africa (91.7%). Surgeons reported an average of 6.7 ± 4.9 on-call shifts per month, with European and North American surgeons experiencing 6.5 ± 4.9 and 7.8 ± 4.1 on-calls monthly, respectively. African surgeons had the highest on-call frequency (8.7 ± 6.1). Post-on-call, only 35.1% of respondents received a day off. Europeans were most likely (40%) to have a day off, while African surgeons were least likely (6.7%). On the adjusted multivariable analysis HDI (Human Development Index) (aOR 1.993) hospital capacity > 400 beds (aOR 2.423), working in a specialty surgery unit (aOR 2.087), and making the on-call in-house (aOR 5.446), significantly predicted the likelihood of having a day off after an on-call shift. Our study revealed critical insights into the disparities in workload, access to research, and professional opportunities for surgeons across different continents, underscored by the HDI
Diagnosis of Noonan syndrome and related disorders using target next generation sequencing
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