Prospective follow-up in various subtypes of cardiomyopathies: Insights from the ESC EORP Cardiomyopathy Registry

Aims: The European Society of Cardiology (ESC) European Observational Research Programme (EORP) Cardiomyopathy Registry is a prospective multinational registry of consecutive patients with cardiomyopathies. The objective of this report is to describe the short-term outcomes of adult patients (≥18 years old). Methods and results: Out of 3208 patients recruited, follow-up data at 1 year were obtained in 2713 patients (84.6%) [1420 with hypertrophic (HCM); 1105 dilated (DCM); 128 arrhythmogenic right ventricular (ARVC); and 60 restrictive (RCM) cardiomyopathies]. Improvement of symptoms (dyspnoea, chest pain, and palpitations) was globally observed over time (P < 0.05 for each). Additional invasive procedures were performed: prophylactic implantation of implantable cardioverter-defibrillator (ICD) (5.2%), pacemaker (1.2%), heart transplant (1.1%), ablation for atrial or ventricular arrhythmia (0.5% and 0.1%). Patients with atrial fibrillation increased from 28.7% to 32.2% of the cohort. Ventricular arrhythmias (VF/ventricular tachycardias) in ICD carriers (primary prevention) at 1 year were more frequent in ARVC, then in DCM, HCM, and RCM (10.3%, 8.2%, 7.5%, and 0%, respectively). Major cardiovascular events (MACE) occurred in 29.3% of RCM, 10.5% of DCM, 5.3% of HCM, and 3.9% of ARVC (P < 0.001). MACE were more frequent in index patients compared to relatives (10.8% vs. 4.4%, P < 0.001), more frequent in East Europe centres (13.1%) and least common in South Europe (5.3%) (P < 0.001). Subtype of cardiomyopathy, geographical region, and proband were predictors of MACE on multivariable analysis. Conclusions: Despite symptomatic improvement, patients with cardiomyopathies remain prone to major clinical events in the short term. Outcomes were different not only according to cardiomyopathy subtypes but also in relatives vs. index patients, and according to European regions

The Rewiring of Ubiquitination Targets in a Pathogenic Yeast Promotes Metabolic Flexibility, Host Colonization and Virulence

Funding: This work was funded by the European Research Council [http://erc.europa.eu/], AJPB (STRIFE Advanced Grant; C-2009-AdG-249793). The work was also supported by: the Wellcome Trust [www.wellcome.ac.uk], AJPB (080088, 097377); the UK Biotechnology and Biological Research Council [www.bbsrc.ac.uk], AJPB (BB/F00513X/1, BB/K017365/1); the CNPq-Brazil [http://cnpq.br], GMA (Science without Borders fellowship 202976/2014-9); and the National Centre for the Replacement, Refinement and Reduction of Animals in Research [www.nc3rs.org.uk], DMM (NC/K000306/1). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Acknowledgments We thank Dr. Elizabeth Johnson (Mycology Reference Laboratory, Bristol) for providing strains, and the Aberdeen Proteomics facility for the biotyping of S. cerevisiae clinical isolates, and to Euroscarf for providing S. cerevisiae strains and plasmids. We are grateful to our Microscopy Facility in the Institute of Medical Sciences for their expert help with the electron microscopy, and to our friends in the Aberdeen Fungal Group for insightful discussions.Peer reviewedPublisher PD

Translational selection on SHH genes

Codon usage bias has been observed in various organisms. In this study, the correlation between SHH genes expression in some tissues and codon usage features was analyzed by bioinformatics. We found that translational selection may act on compositional features of this set of genes

Does codon bias have an evolutionary origin?

<p>Abstract</p> <p>Background</p> <p>There is a 3-fold redundancy in the Genetic Code; most amino acids are encoded by more than one codon. These synonymous codons are not used equally; there is a Codon Usage Bias (CUB). This article will provide novel information about the origin and evolution of this bias.</p> <p>Results</p> <p>Codon Usage Bias (CUB, defined here as deviation from equal usage of synonymous codons) was studied in 113 species. The average CUB was 29.3 ± 1.1% (S.E.M, n = 113) of the theoretical maximum and declined progressively with evolution and increasing genome complexity. A Pan-Genomic Codon Usage Frequency (CUF) Table was constructed to describe genome-wide relationships among codons. Significant correlations were found between the number of synonymous codons and (i) the frequency of the respective amino acids (ii) the size of CUB. Numerous, statistically highly significant, internal correlations were found among codons and the nucleic acids they comprise. These strong correlations made it possible to predict missing synonymous codons (wobble bases) reliably from the remaining codons or codon residues.</p> <p>Conclusion</p> <p>The results put the concept of "codon bias" into a novel perspective. The internal connectivity of codons indicates that all synonymous codons might be integrated parts of the Genetic Code with equal importance in maintaining its functional integrity.</p

SEROLOGICAL DETECTION OF HEPATITIS A VIRUS IN FREE-RANGING NEOTROPICAL PRIMATES (Sapajus spp., Alouatta caraya) FROM THE PARANÁ RIVER BASIN, BRAZIL

Nonhuman primates are considered as the natural hosts of Hepatitis A virus (HAV), as well as other pathogens, and can serve as natural sentinels to investigate epizootics and endemic diseases that are of public health importance. During this study, blood samples were collected from 112 Neotropical primates (NTPs) (Sapajus nigritus and S. cay, n = 75; Alouatta caraya, n = 37) trap-captured at the Paraná River basin, Brazil, located between the States of Paraná and Mato Grosso do Sul. Anti-HAV IgG antibodies were detected in 4.5% (5/112) of NTPs, specifically in 6.7% (5/75) of Sapajus spp. and 0% (0/37) of A. caraya. In addition, all samples were negative for the presence of IgM anti-HAV antibodies. These results suggest that free-ranging NTPs were exposed to HAV within the geographical regions evaluated

Subarachnoidal Neurocysticercosis non-responsive to cysticidal drugs: a case series

<p>Abstract</p> <p>Background</p> <p>Neurocysticercosis (NC) is one of the most frequent parasitic diseases of the central nervous system. Cysticidal drugs, albendazole and praziquantel, are generally effective when parasites localize in the parenchyma. In contrast, parasites lodged in the subarachnoid basal cisterns are less responsive to treatment.</p> <p>Case Presentation</p> <p>The clinical and radiological pictures of six Mexican patients non-respondent to cysticidal treatment are presented.</p> <p>Conclusions</p> <p>The possible factors involved in the cysticidal non-response are discussed and hints are provided of potentially useful changes to therapeutic protocols.</p

Generic Algorithm to Predict the Speed of Translational Elongation: Implications for Protein Biogenesis

Synonymous codon usage and variations in the level of isoaccepting tRNAs exert a powerful selective force on translation fidelity. We have developed an algorithm to evaluate the relative rate of translation which allows large-scale comparisons of the non-uniform translation rate on the protein biogenesis. Using the complete genomes of Escherichia coli and Bacillus subtilis we show that stretches of codons pairing to minor tRNAs form putative sites to locally attenuate translation; thereby the tendency is to cluster in near proximity whereas long contiguous stretches of slow-translating triplets are avoided. The presence of slow-translating segments positively correlates with the protein length irrespective of the protein abundance. The slow-translating clusters are predominantly located down-stream of the domain boundaries presumably to fine-tune translational accuracy with the folding fidelity of multidomain proteins. Translation attenuation patterns at highly structurally and functionally conserved domains are preserved across the species suggesting a concerted selective pressure on the codon selection and species-specific tRNA abundance in these regions