Sex-related differences of fatty acid-binding protein 4 and leptin levels in atrial fibrillation.

AIMS: Adiposity plays a key role in the pathogenesis of atrial fibrillation (AF). Our aim was to study the sex differences in adipokines levels according to AF burden. METHODS AND RESULTS: Two independent cohorts of patients were studied: (i) consecutive patients with AF undergoing catheter ablation (n = 217) and (ii) a control group (n = 105). (i) Adipokines, oxidative stress, indirect autonomic markers, and leucocytes mRNA levels were analysed; (ii) correlation between biomarkers was explored with heatmaps and Kendall correlation coefficients; and (iii) logistic regression and random forest model were used to determine predictors of AF recurrence after ablation. Our results showed that: (i) fatty acid-binding protein 4 (FABP4) and leptin levels were higher in women than in men in both cohorts (P < 0.01). In women, FABP4 levels were higher on AF cohort (20 ± 14 control, 29 ± 18 paroxysmal AF and 31 ± 17 ng/mL persistent AF; P < 0.01). In men, leptin levels were lower on AF cohort (22 ± 15 control, 13 ± 16 paroxysmal AF and 13 ± 11 ng/mL persistent AF; P < 0.01). (ii) In female with paroxysmal AF, there was a lower acetylcholinesterase and higher carbonic anhydrase levels with respect to men (P < 0.05). (iii) Adipokines have an important role on discriminate AF recurrence after ablation. In persistent AF, FABP4 was the best predictor of recurrence after ablation (1.067, 95% confidence interval 1-1.14; P = 0.046). CONCLUSION: The major finding of the present study is the sex-based differences of FABP4 and leptin levels according to AF burden. These adipokines are associated with oxidative stress, inflammatory and autonomic indirect markers, indicating that they may play a role in AF perpetuation.

A haplotype containing the p53 polymorphisms Ins16bp and Arg72Pro modifies cancer risk in BRCA2 mutation carriers.

Germline mutations in the BRCA1 and BRCA2 genes confer a high lifetime risk of developing breast and other cancers; however, remarkable differences exist regarding disease manifestation in mutation carriers. It has been suggested that other genetic and/or environmental factors modify not only the appearance but also the age of onset and type of tumor in BRCA1/2-associated cases. The aim of the present study was to investigate the role of two p53 polymorphisms (c.97-147ins16bp and c.215c>g, p.Arg72Pro) as potential modifiers. For this purpose we investigated the possible association between the two polymorphisms and disease status in 447 BRCA1/2 mutation carriers belonging to 170 Spanish breast and/or ovarian cancer families. Genotype and haplotype analyses revealed that the presence of a specific haplotype carrying the allele without the 16-bp insertion and the variant allele for the Arg72Pro (No Ins-72Pro haplotype) was associated with an earlier age of onset in BRCA2 mutation carriers. We found an increased risk of developing a first primary tumor (breast or ovarian) before 35 years of age for individuals who carried at least one No Ins-72Pro haplotype (OR: 2.69; 95% CI: 1.15-6.29; P=0.022). We confirmed these data by a functional study in which we compared different p53 genotypes in relation to their apoptotic response after cell treatment with a cytotoxic drug (AraC). Our results revealed a decrease in p53 apoptotic rate associated with the No Ins-72Pro haplotype.

Understanding the cytological diploidization mechanism of polyploid wild wheats.

The allohexaploid Aegilops species (2n = 6x = 42), Ae. neglecta 6x (UUXtXtNN), Ae. juvenalis (DcDcXcXcUU), and Ae. vavilovii (DcDcXcXcSsSs) regularly form bivalents at metaphase I. However, in Ae. crassa 6x (DcDcXcXcDD) 0.27 quadrivalents per cell were observed probably as a consequence of the partial homology displayed by the D and Dc genomes. Likewise, the synthetic amphiploid Ae. ventricosa-Secale cereale (DDNNRR) is fertile and displays a diploid-like behavior at metaphase I, despite its recent origin. The pattern of synapsis at late zygotene and pachytene in the natural and artificial allohexaploids was analyzed by whole-mount surface-spreading of synaptonemal complexes under an electron microscope. It revealed that chromosomes were mostly associated as bivalents in all cases, the mean of multivalents per nucleus ranging from 0.17 (Ae. neglecta 6x) to 1.03 (Ae. crassa 6x) in the natural species and 1.05 in the Ae. ventricosa-S. cereale amphiploid. It can be concluded that the mechanism controlling bivalent formation in these species and also in the synthetic amphiploid acts mainly at zygotene by restricting synapsis to homologous chromosomes, but also acts at pachytene by preventing chiasma formation in the homoeologous associations. These observations are discussed in relation to the origin and evolution of the mechanism of diploidization in the allopolyploid species of the Poaceae family.

[Beta-blockers in cardiac insufficiency: should they always be considered in the therapeutic strategy? Arguments against]. / Betabloqueantes en la insuficiencia cardíaca: deben incluirse siempre en la estrategia terapéutica? Argumentos en contra.

The evidence supporting the use of beta-adrenergic blockers in the treatment of heart failure secondary to systolic dysfunction is reviewed. Up to date, seven controlled trials of carvedilol in patients with heart failure have been published. It has been concluded that the use of the non-selective, third generation beta-adrenergic blockers, with alpha-adrenergic (vasodilator) and antioxidant properties, carvedilol, is only justified in patients with mild or moderate heart failure without contraindications to beta-adrenergic blockers. There are not data to support the use of carvedilol in patients with severe or unstable heart failure. It seems logical to wait for the results of the ongoing trials (BEST Trial, CIBIS II Trial, COMET Trial, and MERIT Trial) to more precisely define the role that beta-adrenergic blockers should play in the treatment of patients with heart failure. The information presently available suggests that carvedilol should be considered a therapeutic agent for the prevention of progressive clinical heart failure rather than for the treatment of refractory heart failure.

[Valve repair in tricuspid endocarditis in the drug addict. Apropos a case]. / Reparación valvular en la endocarditis tricúspide del drogadicto. A propósito de un caso.

Valve replacement, valvulectomy and valve repair are the alternatives for the surgical treatment of intractable tricuspid valve endocarditis. We present the case of a 24-year-old, HIV-positive Caucasian female, intravenous drug addict, with intractable tricuspid valve endocarditis, that was successfully treated with tricuspid valve repair. Advantages and major drawbacks of the different techniques are discussed and the appropriate literature is reviewed.

Single-cell genetic analysis reveals the composition of initiating clones and phylogenetic patterns of branching and parallel evolution in myeloma.

Although intratumor heterogeneity has been inferred in multiple myeloma (MM), little is known about its subclonal phylogeny. To describe such phylogenetic trees in a series of patients with MM, we perform whole-exome sequencing and single-cell genetic analysis. Our results demonstrate that at presentation myeloma is composed of two to six different major clones, which are related by linear and branching phylogenies. Remarkably, the earliest myeloma-initiating clones, some of which only had the initiating t(11;14), were still present at low frequencies at the time of diagnosis. For the first time in myeloma, we demonstrate parallel evolution whereby two independent clones activate the RAS/MAPK pathway through RAS mutations and give rise subsequently to distinct subclonal lineages. We also report the co-occurrence of RAS and interferon regulatory factor 4 (IRF4) p.K123R mutations in 4% of myeloma patients. Lastly, we describe the fluctuations of myeloma subclonal architecture in a patient analyzed at presentation and relapse and in NOD/SCID-IL2Rγ(null) xenografts, revealing clonal extinction and the emergence of new clones that acquire additional mutations. This study confirms that myeloma subclones exhibit different survival properties during treatment or mouse engraftment. We conclude that clonal diversity combined with varying selective pressures is the essential foundation for tumor progression and treatment resistance in myeloma.

Tratamiento de las úlceras por presión con Aloe Vera / No disponible

Objetivos: Presentar una información actualizada acerca de la aplicación del Aloe Vera en las úlceras por presión (UPP). Material y métodos: Búsqueda bibliográfica de los artículos publicados, entre 2004 y 2014, en diferentes bases de datos biomédicas. Resultados: La evidencia confirma que puede ayudar en la prevención y en el tratamiento de UPP de grado I y II. Sin embargo no existen referencias que justifiquen su uso en las UPP III y IV. Conclusiones: La Organización Mundial de la Salud (OMS) recomienda a los gobiernos que sitúen la seguridad del paciente en el centro de las Políticas Sanitarias, destacando medidas cómo la prevención y el tratamiento de las UPP

Objectives: To show updated information about the implementation of Aloe Vera in the treatment of pressure ulcers. Material and methods: Literature search of articles published, between 2004 and 2014, in different biomedical databases. Results: The evidence confirms that Aloe Vera can help in the prevention and treatment of pressure ulcers of grade I and II. However, there are no references that justify its use in pressure ulcers III and IV. Conclusions: The World Health Organization (WHO) recommends that governments put patient safety at the center of Health Policy, emphasizing measures like prevention and treatment of pressure ulcers

Distinct genomic aberration patterns are found in familial breast cancer associated with different immunohistochemical subtypes.

Five breast cancer subtypes have been described in sporadic breast cancer (SBC) using expression arrays: basal-like, ERBB2, normal breast-like, luminal A and B. These molecular subtypes show different genomic aberration patterns (GAPs). Recently, our group described these breast cancer subtypes in 50 non-BRCA1/2 familial tumors using immunohistochemistry assays. We extended this study to the other classes of familial breast cancer (FBC), including 62 tumors (18 BRCA1, 16 BRCA2 and 28 non-BRCA1/2), with the same panel of 25 immunohistochemical (IHC) markers and histological grade obtaining a similar classification. We combined these data with results generated by a 1 Mb BAC array-based CGH study to evaluate the genomic aberrations of each group. We found that BRCA1-related tumors are preferentially basal-like, whereas non-BRCA1/2 familial tumors are mainly luminal A subtype. We described distinct GAPs related to each IHC subtype. Basal tumors had a greater number of gains/losses, while luminal B tumors had more high-level DNA amplifications. Our data are similar to those obtained in SBC studies, highlighting the existence of distinct genetic pathways of tumor evolution, common to both SBC and FBC.

VDD pacing with single lead in a heart transplant recipient: case report.

Permanent pacemaker implantation is required in a large number of transplantation patients principally because of sinus node dysfunction of the donor atrium. The most suitable mode of pacing in these cases is still subject to controversy. We describe one case of a single lead system of VDD stimulation and sensing of the recipient atrial signal in a 32-year-old patient with posttransplant symptomatic sinus node dysfunction. Physiological adaptation of rate was achieved with recovery of normal receptor sinus node function.