Large Genomic Imbalances in Brugada Syndrome

Purpose Brugada syndrome (BrS) is a form of cardiac arrhythmia which may lead to sudden cardiac death. The recommended genetic testing (direct sequencing of SCN5A) uncovers disease-causing SNVs and/or indels in ~20% of cases. Limited information exists about the frequency of copy number variants (CNVs) in SCN5A in BrS patients, and the role of CNVs in BrS-minor genes is a completely unexplored field. Methods 220 BrS patients with negative genetic results were studied to detect CNVs in SCN5A. 63 cases were also screened for CNVs in BrS-minor genes. Studies were performed by Multiplex ligation-dependent probe amplification or Next-Generation Sequencing (NGS). Results The detection rate for CNVs in SCN5A was 0.45% (1/220). The detected imbalance consisted of a duplication from exon 15 to exon 28, and could potentially explain the BrS phenotype. No CNVs were found in BrS-minor genes. Conclusion CNVs in current BrS-related genes are uncommon among BrS patients. However, as these rearrangements may underlie a portion of cases and they undergo unnoticed by traditional sequencing, an appealing alternative to conventional studies in these patients could be targeted NGS, including in a single experiment the study of SNVs, indels and CNVs in all the known BrS-related genes

Coordination of subjects in the program as a formative activity of the multidisciplinary educational team for the degree in Pharmacy

La Universidad de Granada, dentro del Plan Estratégico y el Contrato Programa 2007-2011 de las Universidades Públicas de Andalucía puso en marcha la convocatoria de apoyo a la formación del profesorado principiante y mejora de la docencia por el Vicerrectorado para la Garantía de la Calidad (http://calidad.ugr.es/pages/secretariados/form_apoyo_calidad/apoyo_formacion_principiante/convoca toria). En el proyecto participan 15 profesores, 5 profesores experimentados y 10 profesores noveles de seis departamentos diferentes.. Entre los objetivos se incluye la optimización de la actividad docente de profesorado principiante. En este sentido se estudió la situación en el nuevo plan de estudio de Grado en Farmacia de las asignaturas que dichos profesores impartimos, así como la relación entre ellas y la posible existencia de solapamientos de contenidos docentes. Las fichas docentes muestran ciertos solapamientos de competencias y carencias en algunos casos. Esto supuso una revisión exhaustiva para llevar a cabo una correcta coordinación entre los profesores que le permita al alumnado un aprendizaje organizado y coherente.The University of Granada, inside the Strategic Plan and the Contract Program 2007-2011 of the Public Universities of Andalusia started a public call to improve the formation of young lecturers and the teaching activity (http://calidad.ugr.es/pages/secretariados/form_apoyo_calidad/apoyo_formacion_principiante/convoca toria). In the project there take part 15 lecturers, 5 experienced and 10 young lecturers from six different departments. Within the objectives it is included the optimisation of the teaching activity of young lecturers. In this sense, it was studied the situation of the subjects that the above mentioned lecturers give within the new degree in Pharmacy, as well as the relation between they and the possible existence of any overlapping in the contents. The teaching contents showed the existence of certain overlapping within competences and deficiencies in some cases. This supposed an exhaustive review to carry out the correct coordination between the different lecturers so that it will allow the organized and coherent learning of the students

Role of age and comorbidities in mortality of patients with infective endocarditis

[Purpose]: The aim of this study was to analyse the characteristics of patients with IE in three groups of age and to assess the ability of age and the Charlson Comorbidity Index (CCI) to predict mortality. [Methods]: Prospective cohort study of all patients with IE included in the GAMES Spanish database between 2008 and 2015.Patients were stratified into three age groups:<65 years,65 to 80 years,and ≥ 80 years.The area under the receiver-operating characteristic (AUROC) curve was calculated to quantify the diagnostic accuracy of the CCI to predict mortality risk. [Results]: A total of 3120 patients with IE (1327 < 65 years;1291 65-80 years;502 ≥ 80 years) were enrolled.Fever and heart failure were the most common presentations of IE, with no differences among age groups.Patients ≥80 years who underwent surgery were significantly lower compared with other age groups (14.3%,65 years; 20.5%,65-79 years; 31.3%,≥80 years). In-hospital mortality was lower in the <65-year group (20.3%,<65 years;30.1%,65-79 years;34.7%,≥80 years;p < 0.001) as well as 1-year mortality (3.2%, <65 years; 5.5%, 65-80 years;7.6%,≥80 years; p = 0.003).Independent predictors of mortality were age ≥ 80 years (hazard ratio [HR]:2.78;95% confidence interval [CI]:2.32–3.34), CCI ≥ 3 (HR:1.62; 95% CI:1.39–1.88),and non-performed surgery (HR:1.64;95% CI:11.16–1.58).When the three age groups were compared,the AUROC curve for CCI was significantly larger for patients aged <65 years(p < 0.001) for both in-hospital and 1-year mortality. [Conclusion]: There were no differences in the clinical presentation of IE between the groups. Age ≥ 80 years, high comorbidity (measured by CCI),and non-performance of surgery were independent predictors of mortality in patients with IE.CCI could help to identify those patients with IE and surgical indication who present a lower risk of in-hospital and 1-year mortality after surgery, especially in the <65-year group

Bioavailability and biotransformation of linolenic acid from basil seed oil as a novel source of omega-3 fatty acids tested on a rat experimental model.

Basil is an aromatic herb with a high concentration of bioactive compounds. The oil extracted from its seeds is a good source of α-linolenic acid (ALA) and also provides substantial amounts of linoleic acid (LA). This study aimed to test the bioavailability of the oil derived from basil seeds and its effects on different physiological parameters using 7-15% dietary inclusion levels. Furthermore, the assimilation of LA and ALA and their transformation in long-chain polyunsaturated fatty acids (LC-PUFAs) have been studied. Digestive utilization of total fat from basil seed oil (BSO) was high and similar to that of olive oil used as a control. Consumption of BSO resulted in increased LA and ALA levels of the plasma, liver, and erythrocyte membrane. In addition, the transformation of LA to arachidonic acid (ARA) was decreased by the high dietary intake of ALA which redirected the pathway of the Δ-6 desaturase enzyme towards the transformation of ALA into eicosapentaenoic acid (EPA). No alterations of hematological and plasma biochemical parameters were found for the 7 and 10% dietary inclusion levels of BSO, whereas a decrease in the platelet count and an increase in total- and HDL-cholesterol as well as plasma alkaline phosphatase (ALP) were found for a 15% BSO dose. In conclusion, BSO is a good source of ALA to be transformed into EPA and decrease the precursor of the pro-inflammatory molecule ARA. This effect on the levels of EPA in different tissues offers potential for its use as a dietary supplement, novel functional food, or a constituent of nutraceutical formulations to treat different pathologies

Synthesis of [77Se]-methylselenocysteine when preparing sauerkraut in the presence of [77Se]-selenite. Metabolic transformation of [77Se]-methylselenocysteine in Wistar rats determined by LC-IDA-ICP-MS

© 2014 Springer-Verlag Berlin Heidelberg. The use of enriched Se isotopes as tracers has provided important information on Se metabolism. However, selenium isotopes are expensive and difficult to obtain. A simple and cheap strategy based on the production of [77Se]-methylselenocysteine ([77Se]-MeSeCys) when preparing sauerkraut in the presence of [77Se]-selenite was developed. The resulting [77Se]-MeSeCys was used for evaluating the metabolic transformation of MeSeCys in Wistar rats, by feeding them with an AIN-93 M diet containing 20 % sauerkraut enriched in [77Se]-MeSeCys. Organs (liver, kidney, brain, testicles, and heart) were obtained after seven days of treatment and subjected to total selenium and selenium-speciation analysis by high-performance liquid chromatography coupled with isotope-dilution-analysis inductively-coupled-plasma mass spectrometry (HPLC-IDA-ICP-MS). Analysis of 77Se-labeled organs revealed a prominent increase (more than 100 % Se-level enhancement) of selenium in the kidney and heart, whereas in the liver selenium concentration only increased by up to 20 % and it remained constant in the brain and testicles. 77Se-enriched-sauerkraut supplementation does not alter the concentration of other essential elements in comparison to controls except for in the heart and kidney, in which selenium was positively correlated with Mg, Zn, Cu, and Mo. HPLC-ICP-MS analysis of hydrolyzed extracts after carbamidomethylation of the 77Se-labeled organs revealed the presence of [77Se]-SeCys and an unknown Se-containing peak, the identity of which could not be verified by electrospray-ionization (ESI)-MS-MS. Low amounts of [77Se]-MeSeCys were found in 77Se-labeled liver and kidney extracts, suggesting the incorporation of this selenium species in its intact form.The Complutense University Group of Trace and Speciation Analysis thanks the Spanish Commission of Science and Technology (CTQ2011-22732), the Community of Madrid, Spain, and the European Community for funding the FEDER programme (S2010/ AGR-1464, ANALYSIC II). María Sánchez-Martínez would also like to thank the Spanish Government for a doctoral fellowship (CTQ2008- 05925). This research was also funded by project AGL2007-62044 from the Spanish Ministry of Education and Science.Peer Reviewe

Metabolismo de la SeMeSeCys en ratas alimentadas con chucrut enriquecido en 77Se

Trabajo presentado a la XVIII Reunión de la Asociación Española de Química Analítica, celebrada en Úbeda (España) en Junio de 2013.Peer reviewe

SeMeSeCys metabolismin rats fed with 77Se-enriched sauerkraut

Resumen del póster presentado a la European Winter Conference on Plasma Spectrochemistry, celebrada en Krakow (Polonia) del 10 al 15 de febrero de 2013.Selenium (Se), an essential trace element for human health, has a well-known role in prevention of chronic diseases associated with oxidative stress and inflammation. As several millions of people worldwide do not reach the RDA of selenium, intake of Se supplements has been the most widespread approach to prevent Se deficiency. Several authors have reported preparation of Se-enriched foods by fermentation processes. Fermented white cabbage, "sauerkraut", a traditional North-East European food product with nutritional and health-promoting properties, has been prepared in presence of seleniuro salt (Na2SeOJ) providing important amounts of SeMeSeCys. This Se species is recognized to have anticarcinogenic properties and, hence, consumption sauerkraut will contribute to the population well-being. Nevertheless, fuere is a lack of knowledge about Se metabolism, distribution and safety in living organisms. Therefore, the aim of this work was to establish the metabolism of SeMeSeCys in rats fed with Se-enriched sauerkraut and to assess its distribution in different body organs. Wistar rats weighing about 150g were fed ad libitum with a standard AIN-93M diet containing 77Se-enriched sauerkraut (20%) for an experimental period of 7 days. During the experiment, weight gain and the intake of food and water were monitored. On day seven, the rats were sacrificed and the organs were removed for further selenium distribution analysis. For this purpose, an analytical methodology based on previous works for trace element determination in rat tissues was applied. In the present communication, bioaccumulation and distribution of exogenous (7Se) and endogenous seleniurn in different organs as liver, heart, brain, testicles, etc. as total selenium using HG-AFS and IDA-ICP-MS will be reported. Se-species identification in the different organs will be performed by applying several sample treatments and chromatographic columns of different mechanisrns. Quantification of the Se-species will be carried out by IDA in combination with LC-ICP-MS. The results obtained will achieve deeper insights about the metabolisrns of SeMetSeCys in living organisms.Peer reviewe

Colon cancer therapy with calcium phosphate nanoparticles loading bioactive compounds from Euphorbia lathyris: In vitro and in vivo assay.

Amorphous calcium phosphate nanoparticles (ACP NPs) exhibit excellent biocompatibility and biodegradability properties. ACP NPs were functionalized with two coumarin compounds (esculetin and euphorbetin) extracted from Euphorbia lathyris seeds (BC-ACP NPs) showing high loading capacity (0.03% and 0.34% (w/w) for esculetin and euphorbetin, respectively) and adsorption efficiency (2.6% and 33.5%, respectively). BC-ACP NPs, no toxic to human blood cells, showed a more selective cytotoxicity against colorectal cancer (CRC) cells (T-84 cells) (IC50, 71.42 µg/ml) compared to non-tumor (CCD18) cells (IC50, 420.77 µg/ml). Both, the inhibition of carbonic anhydrase and autophagic cell death appeared to be involved in their action mechanism. Interestingly, in vivo treatment with BC-ACPs NPs using two different models of CRC induction showed a significant reduction in tumor volume (62%) and a significant decrease in the number and size of polyps. A poor development of tumor vasculature and invasion of normal tissue were also observed. Moreover, treatment increased the bacterial population of Akkermansia by restoring antioxidant systems in the colonic mucosa of mice. These results show a promising pathway to design innovative and more efficient therapies against CRC based on biomimetic calcium phosphate NPs loaded with natural products

Sex-Specific Ventricular Arrhythmias and Mortality in Cardiac Resynchronization Therapy Recipients

OBJECTIVES The study goal was to examine whether there are sex-related differences in the incidence of ventricular arrhythmias and mortality in CRT-defibrillator (CRT-D) recipients. BACKGROUND Few studies have evaluated sex-related benefits of cardiac resynchronization therapy (CRT). Moreover, data on sex-related differences in the occurrence of ventricular tachyarrhythmias in this population are limited. METHODS A multicenter retrospective study was conducted in 460 patients (355 male subjects and 105 female sub- jects) from the UMBRELLA (Incidence of Arrhythmia in Spanish Population With a Medtronic Implantable Cardiac Defi- brillator Implant) national registry. Patients were followed up through remote monitoring after the first implantation of a CRT-D during a median follow-up of 2.2 1.0 years. Sex differences were analyzed in terms of ventricular arrhythmia– treated incidence and death during the follow-up period, with a particular focus on primary prevention patients. RESULTS Baseline New York Heart Association functional class was worse in women compared with that in men (67.0% of women in New York Heart Association functional class III vs. 49.7% of men; p ¼ 0.003), whereas women had less ischemic cardiac disease (20.8% vs. 41.7%; p < 0.001). Female sex was an independent predictor of ventricular ar- rhythmias (hazard ratio: 0.40; 95% confidence interval: 0.19 to 0.86; p ¼ 0.020), as well as left ventricular ejection fraction and nonischemic cardiomyopathy. Mortality in women was one-half that of men, although events were scarce and without significant differences (2.9% vs. 5.6%; p ¼ 0.25). CONCLUSIONS Women with left bundle branch block and implanted CRT have a lower rate of ventricular tachyarrhythmias than men. All-cause mortality in patients is, at least, similar between female and male subjects.Medicin

Metabolically healthy obesity: Inflammatory biomarkers and adipokines in elderly population.

Obesity is linked to elevated levels of inflammatory serum markers such as C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor alpha (TNFa). Adiponectin and resistin are adipokines related to obesity. It has been described that adipose tissue presents a high production and secretion of these diverse pro-inflammatory molecules, which may have local effects on the physiology of fat cells as well as systemic effects on other organs. Our aim was to evaluate the impact that lifestyle modifications, by following a Mediterranean Diet (MedDiet) program and physical activity (PA) training, would have on inflammatory biomarkers and adipokine profile in a Metabolically Healthy Obese (MHO) elderly population from Malaga (Andalusia, Spain). Subjects aged ≥65 years (65 to 87 years old) with obesity (BMI ≥30 kg/m2) were included in this study if they met ≤1 of the following criteria: systolic blood pressure ≥130 mmHg and/or diastolic blood pressure ≥ 85 mmHg; triglycerides ≥150 mg/dL; HDL-C 166 MHO elderly subjects, 40 (24.1%) male and 126 (75.9%) female (p Healthy aging is a multifactorial biological process in which lifestyle is essential. The presence of obesity in elderly metabolically healthy population is not a problem necessarily. Elderly MHO population who eat a MedDiet and practice regularly PA are capable to modulate their production of inflammatory cytokines (CRP, IL-6, TNFa) and adipokines profile (adiponectin, resistin), preventing other metabolic disorders