Cinco años de investigaciones en "El Charcón" (Alozaina, Málaga) : (1999-2004)

En este artículo realizamos una revisión de los trabajos e investigaciones arqueológicas llevadas a cabo en el yacimiento neolítico al aire libre de El Charcón de Cerro Ardite (Alozaina, Málaga), desde que en 1999 se diese a conocer dicho yacimiento hasta el estudio del material cerámico, finalizado en 2004. Estos últimos trabajos son fruto de una prospección intensiva y sistemática a la cual dedicaremos la mayor parte de nuestro estudio y gracias a la cual hemos podido documentar una gran diversidad de materiales arqueológicos; dado el estado actual de la investigación del yacimiento, nos centraremos en el estudio de la cerámica decorada. Del mismo modo, dicha prospección nos ha facilitado proponer un encuadre crono-cultural del yacimiento constituido por dos fases: Neolítico Antiguo-Medio y Neolítico Final-Cobre Antiguo. Para finalizar, expondremos los trabajos que a medio plazo se pretenden llevar a cabo en este yacimiento teniendo en cuenta el potencial arqueológico estimado para el mismo.In this article we present a revision of the archaeological research and works carried out at the open-air neolithic site called El Charcón at Cerro Ardite (Alozaina, Málaga), from 1999, when the site was discovered, to 2004, when a survey of the Neolithic pottery present at the site was finished. This article stresses the importance of an intensive and systematic prospection executed in 2001, which provided us a lot of data about prehistoric material culture at the site; because of the current state of the research, we will focus particularly in studying shards with decoration. Moreover, the prospection allowed us to make a proposal regarding the chronology of the site, consisting of two phases: Early-Medium Neolithic and Late Neolithic-Early Copper Age. Finally, we will present our medium-term objectives for the future of the site, taking into account its estimated archaeological potential

Emery-Dreifuss muscular dystrophy Type 1 is associated with a high risk of malignant ventricular arrhythmias and end-stage heart failure

BACKGROUND AND AIMS: Emery-Dreifuss muscular dystrophy (EDMD) is caused by variants in EMD (EDMD1) and LMNA (EDMD2). Cardiac conduction defects and atrial arrhythmia are common to both, but LMNA variants also cause end-stage heart failure (ESHF) and malignant ventricular arrhythmia (MVA). This study aimed to better characterise the cardiac complications of EMD variants. METHODS: Consecutively referred EMD variant-carriers were retrospectively recruited from 12 international cardiomyopathy units. MVA and ESHF incidence in male and female variant-carriers was determined. Male EMD variant-carriers with a cardiac phenotype at baseline (EMDCARDIAC) were compared to consecutively recruited male LMNA variant-carriers with a cardiac phenotype at baseline (LMNACARDIAC). RESULTS: Longitudinal follow-up data were available for 38 male and 21 female EMD variant-carriers (mean [SD] ages 33.4 [13.3] and 43.3 [16.8] years, respectively). Nine (23.6%) males developed MVA and five (13.2%) developed ESHF during a median [IQR] follow-up of 65.0 [24.3, 109.5] months. No female EMD variant-carrier had MVA or ESHF, but nine (42.8%) developed a cardiac phenotype at a median [IQR] age of 58.6 [53.2, 60.4] years. Incidence rates for MVA were similar for EMDCARDIAC and LMNACARDIAC (4.8 and 6.6 per 100 person-years, respectively; log-rank p = 0.49). Incidence rates for ESHF were 2.4 and 5.9 per 100 person-years for EMDCARDIAC and LMNACARDIAC, respectively (log-rank p = 0.09). CONCLUSIONS: Male EMD variant-carriers have a risk of progressive heart failure and ventricular arrhythmias similar to that of male LMNA variant-carriers. Early implantable cardioverter defibrillator implantation and heart failure drug therapy should be considered in male EMD variant-carriers with cardiac disease

Clinical presentation of calmodulin mutations: the International Calmodulinopathy Registry

AIMS: Calmodulinopathy due to mutations in any of the three CALM genes (CALM1-3) causes life-threatening arrhythmia syndromes, especially in young individuals. The International Calmodulinopathy Registry (ICalmR) aims to define and link the increasing complexity of the clinical presentation to the underlying molecular mechanisms. METHODS AND RESULTS: The ICalmR is an international, collaborative, observational study, assembling and analysing clinical and genetic data on CALM-positive patients. The ICalmR has enrolled 140 subjects (median age 10.8 years [interquartile range 5-19]), 97 index cases and 43 family members. CALM-LQTS and CALM-CPVT are the prevalent phenotypes. Primary neurological manifestations, unrelated to post-anoxic sequelae, manifested in 20 patients. Calmodulinopathy remains associated with a high arrhythmic event rate (symptomatic patients, n = 103, 74%). However, compared with the original 2019 cohort, there was a reduced frequency and severity of all cardiac events (61% vs. 85%; P = .001) and sudden death (9% vs. 27%; P = .008). Data on therapy do not allow definitive recommendations. Cardiac structural abnormalities, either cardiomyopathy or congenital heart defects, are present in 30% of patients, mainly CALM-LQTS, and lethal cases of heart failure have occurred. The number of familial cases and of families with strikingly different phenotypes is increasing. CONCLUSION: Calmodulinopathy has pleiotropic presentations, from channelopathy to syndromic forms. Clinical severity ranges from the early onset of life-threatening arrhythmias to the absence of symptoms, and the percentage of milder and familial forms is increasing. There are no hard data to guide therapy, and current management includes pharmacological and surgical antiadrenergic interventions with sodium channel blockers often accompanied by an implantable cardioverter-defibrillator

Photosynthetic response to low and high light of cacao growing without shade in an area of low evaporative demand

Cacao (Theobroma cacao L.) breeding programmes in Ecuador have focused on obtaining high-yield clones with improved disease resistance. Cacao clones should also have photosynthetic characteristics which support increased productivity. Regarding the weather conditions at the coast of Ecuador, where most of the year there are overcasts and low air evaporative demand, there is the possibility to grow cacao without overhead shade. This study focused on the photosynthetic response at two different photosynthetic photon flux densities (PPFD) of Ecuadorian cacao clones. Seven-year old cacao clones were evaluated: eight clones of Nacional type and two commercial clones (CCN 51 and EET 103), used as controls. All clones showed an increase of 35 % on average in net photosynthetic rate (A)with increasing PPFD from the light saturation point for cacao (i.e. 400 µmol m-2 s-1) to high values (1000 µmol m-2 s-1). Such light responsiveness in A has not been reported before. Higher A was associated with higher apparent electron transport rate, while high stomatal conductance was maintained under both PPFD conditions. Under high PPFD, low non-photochemical quenching values were found, suggesting low energy dissipation. All clones showed high maximum quantum yields of PSII (Fv/Fm), suggesting the absence of damage of the photochemical system

Clinical characteristics and determinants of the phenotype in TMEM43 arrhythmogenic right ventricular cardiomyopathy type 5.

Arrhythmogenic right ventricular cardiomyopathy type V (ARVC-5) is the most aggressive heterozygous form of ARVC. It is predominantly caused by a fully penetrant mutation (p.S358L) in the nondesmosomal gene TMEM43-endemic to Newfoundland, Canada. To date, all familial cases reported worldwide share a common ancestral haplotype. It is unknown whether the p.S358L mutation by itself causes ARVC-5 or whether the disease is influenced by genetic or environmental factors. The purpose of this study was to examine the phenotype, clinical course, and the impact of exercise on patients with p.S358L ARVC-5 without the Newfoundland genetic background. We studied 62 affected individuals and 73 noncarriers from 3 TMEM43-p.S358L Spanish families. The impact of physical activity on the phenotype was also evaluated. Haplotype analysis revealed that the 3 Spanish families were unrelated to patients with ARVC-5 with the Newfoundland genetic background. Two families shared 10 microsatellite markers in a 4.9 cM region surrounding TMEM43; the third family had a distinct haplotype. The affected individuals showed a 38.7% incidence of sudden cardiac death, which was higher in men. Left ventricular involvement was common, with 40% of mutation carriers showing a left ventricular ejection fraction of <50%. Compared with noncarriers, the R-wave voltage in lead V3 was lower (3.2 ± 2.8 mV vs 7.5 ± 3.6 mV; P < .001) and QRS complex in right precordial leads wider (104.7 ± 24.0 ms vs 88.2 ± 7.7 ms; P = .001). A history of vigorous exercise showed a trend toward more ventricular arrhythmias only in women (P = .053). ARVC-5 is associated with a high risk of sudden cardiac death and characteristic clinical and electrocardiographic features irrespective of geographical origin and genetic background. Our data suggest that, as in desmosomal ARVC, vigorous physical activity could aggravate the phenotype of TMEM43 mutation carriers.This work was supported by grants from the Instituto de Salud Carlos III (PI14/0967 and PI17/1941, CPII14/00027, PI14/01477, PI18/0158 and La Fe Biobank PT17/0015/0043), the Isabel Gemio Foundation, the Spanish Society of Cardiology (2014 Basic Research Grant), the European Union (CardioNeTITN-289600 and CardioNext-608027), and from the Spanish Ministry of Economy and Competitiveness (RTI2018-096961-B-I00, SAF2015-65722-R, and SAF2012-31451). This work was also supported by the Plan Estatal de I1D1I 2013-2016 – European Regional Development Fund (FEDER) “AWay ofMaking Europe,” Spain. The Centro Nacional de Investigaciones Cardiovasculares (CNIC) is supported by the Instituto de Salud Carlos III (ISCIII), the Ministerio de Ciencia, Innovación y Universidades (MCNU), and the ProCNIC Foundation and is a Severo Ochoa Center of Excellence (SEV-2015-0505)S

Syncope and bifascicular block in the absence of structural heart disease.

The treatment of patients with bifascicular block (BFB) and syncope in the absence of structural heart disease (SHD) is not well defined. The objective of our study is to compare pacemaker empirical implantation with the use of electrophysiological studies (EPS). This is a prospective cohort study that included 77 patients with unexplained cardiogenic syncope and BFB without structural heart disease between 1997 and 2012. Two groups: 36 patients received empirical pacemakers (Group A) and 41 underwent EPS (Group B) to guide their treatment. The incidence of syncope recurrence and atrioventricular block was lower in group A. Mortality and complication rates were similar between both groups. Multivariate analysis demonstrated a higher number of events (combined endpoint) in group B. Our study shows that treatment according to EPS does not improve the results of a treatment strategy based on empirical pacemaker

Natural History and Risk Stratification in Andersen-Tawil Syndrome Type 1.

Andersen-Tawil Syndrome type 1 (ATS1) is a rare arrhythmogenic disorder, caused by loss-of-function mutations in the KCNJ2 gene. We present here the largest cohort of patients with ATS1 with outcome data reported. This study sought to define the risk of life-threatening arrhythmic events (LAE), identify predictors of such events, and define the efficacy of antiarrhythmic therapy in patients with ATS1. Clinical and genetic data from consecutive patients with ATS1 from 23 centers were entered in a database implemented at ICS Maugeri in Pavia, Italy, and pooled for analysis. We enrolled 118 patients with ATS1 from 57 families (age 23 ± 17 years at enrollment). Over a median follow-up of 6.2 years (interquartile range: 2.7 to 16.5 years), 17 patients experienced a first LAE, with a cumulative probability of 7.9% at 5 years. An increased risk of LAE was associated with a history of syncope (hazard ratio [HR]: 4.54; p = 0.02), with the documentation of sustained ventricular tachycardia (HR 9.34; p = 0.001) and with the administration of amiodarone (HR: 268; p  Our data demonstrate that the clinical course of patients with ATS1 is characterized by a high rate of LAE. A history of unexplained syncope or of documented sustained ventricular tachycardia is associated with a higher risk of LAE. Amiodarone is proarrhythmic and should be avoided in patients with ATS1