Reporting of conflict of interests, source of funding, and ethics committee approval in randomized trials of three clinical specialties published in Spanish language

Background: Confidence in the results reported by randomized clinical trials (RCTs) depends mainly on the internal validity of the trial and its conduct, but also on other aspects related to health research such as the complete reporting of conflicts of interest (COI), funding sources and approval by ethics committees. Bias in the study results may arise from any one of these elements. Prior studies have explored the reporting of these items in the medical literature, but there are no reports on RCTs published in Spanish and Latin American journals. This study aimed to evaluate the reporting of COIs, funding sources, and approval by ethics committees of RCTs published in Spanish and Latin American journals in dentistry, geriatrics and neurology. Methods: We did a systematic retrospective survey of all RCTs published from 1990 to 2018 in dentistry, neurology, and geriatrics journals published in Spain and Latin America and included in the BADERI database (Iberoamerican journals and trials database by its initials in Spanish). We completed with hand searching. We included RCTs with a recoverable full text published between 1990 and 2018. We extracted data on sources of funding, COI statements, and ethics reviews. The extraction of these items in the RCTs included was done independently by two pairs of reviewers and in parallel for each article, with a third independent reviewer resolving discrepancies. We analysed compliance for each item. Results: We identified RCTs in 69 journals from Spain and Latin American countries. Dentistry accounted for 75% (n = 52) of the journals, neurology 20.6% (n = 14), and geriatrics 4.4% (n = 3). Of the total number of RCTs included in this study (n = 392), only 102 (26%) reported the presence or absence of a COI, 103 (26%) studies reported funding, and 43 (36%) included the ethics committee approval. Conclusions: RCTs published in the Spanish language in dentistry, neurology, and geriatrics had poor compliance with the reporting of a COI, source of funding, and ethics committee approval. Future research should evaluate the accuracy and completeness of COI statements and their relationship to the funding source and direction of the results.

A multiyear systematic survey of the quality of reporting for randomised trials in dentistry, neurology and geriatrics published in journals of Spain and Latin America.

BACKGROUND: The Iberoamerican Cochrane Network is currently developing an extensive project to identify Spanish-language journals that publish original clinical research in Spain and Latin America. The project is called BADERI (Database of Iberoamerican Essays and Journal) and feeds the research articles, mainly randomised clinical trials (RCTs), into CENTRAL (Cochrane Collaboration Central Register of Controlled Trials). This study aims to assess the quality of reporting of RCTs published in Spanish and Latin American journals for three clinical fields and assess changes over time. METHODS: We did a systematic survey with time trend analysis of RCTs for dentistry, geriatrics, and neurology. These fields were chosen for pragmatic reasons as they had not yet been completed in BADERI. After screening RCTs from 1990 to 2018 for randomised or quasi-randomised clinical trials, we extracted data for 23 CONSORT items. The primary outcome was the total score of the 23 predefined CONSORT 2010 items for each RCT (score range from 0 to 34). The secondary outcome measure was the score for each one of these 23 items. RESULTS: A total of 392 articles from 1990 to 2018 were included as follows: dentistry (282), neurology (80), and geriatrics (30). We found that the overall compliance score for the CONSORT items included in this study for all 392 RCTs analysed was 12.6 on a scale with a maximum score of 34. With time, the quality of reporting improved slightly for all RCTs. None of the articles achieved the complete individual CONSORT item compliance score. The lowest overall compliance percentage was for item 10 (Randomisation implementation) and item 24 (Protocol registration), with a dismal 1% compliance across all included RCTs, regardless of country. CONCLUSIONS: CONSORT compliance is very poor in the 392 analysed RCTs. The impact of the CONSORT statement on improving the completeness of RCT reporting in Latin America and Spain is not clear. Iberoamerican journals should become more involved in endorsing and enforcing adherence to the CONSORT guidelines.

Phosphorylation of Phylogenetically Conserved Amino Acid Residues Confines HBx within Different Cell Compartments of Human Hepatocarcinoma Cells.

Hepatitis B virus (HBV) is a circular, and partially double-stranded DNA virus. Upon infection, the viral genome is translocated into the cell nucleus, generating the covalently closed circular DNA (cccDNA) intermediate, and forming a mini chromosome. HBV HBx is a small protein displaying multiple roles in HBV-infected cells, and in different subcellular locations. In the nucleus, the HBx protein is required to initiate and maintain viral transcription from the viral mini chromosome. In contrast, HBx also functions in the cytoplasm, where it is able to alter multiple cellular functions such as mitochondria metabolism, apoptosis and signal transduction pathways. It has been reported that in cultured cells, at low expression levels, the HBx protein is localized in the nucleus, whereas at high expression levels, it accumulates in the cytoplasm. This dynamic subcellular distribution of HBx might be essential to exert its multiple roles during viral infection. However, the mechanism that regulates different subcellular localizations of the HBx protein is unknown. We have previously taken a bioinformatics approach to investigate whether HBx might be regulated via post-translational modification, and we have proposed that the multiple nucleocytoplasmic functions of HBx might be regulated by an evolutionarily conserved mechanism via phosphorylation. In the current study, phylogenetically conserved amino acids of HBx with a high potential of phosphorylation were targeted for site-directed mutagenesis. Two conserved serine (Ser25 and Ser41), and one conserved threonine (Thr81) amino acids were replaced by either alanine or aspartic acid residues to simulate an unphosphorylated or phosphorylated state, respectively. Human hepatoma cells were transfected with increasing amounts of the HBx DNA constructs, and the cells were analyzed by fluorescence microscopy. Together, our results show that the nucleocytoplasmic distribution of the HBx protein could be regulated by phosphorylation since some of the modified proteins were mainly confined to distinct subcellular compartments. Remarkably, both HBx Ser41A, and HBx Thr81D proteins were predominantly localized within the nuclear compartment throughout the different expression levels of HBx mutants.

Modelling of an anaerobic plug-flow reactor. Process analysis and evaluation approaches with non-ideal mixing considerations.

This study shows the implementation of the Anaerobic Digestion Model (ADM1) in an anaerobic plug-flow reactor (PFR) with two approaches based on the use of consecutive continuous stirred tank reactors (CSTR) connected in serie for considering non-ideal mixing. The two-region (TR) model splits each CSTR into two regions, while the particulate retention (PR) model adds a retention parameter. The models were calibrated and validated based on experimental data from a bench-scale reactor treating cow manure. The PFR conventional model slightly outperformed the non-ideal mixing approaches. However, the PR model showed an increase in biomass retention time treating high solid content substrate. Biogas production was not sensitive to variations of the mixing parameters. The liquid fraction content was better represented by the PR model than the PFR and TR models. The study shows how reactor modelling is useful for monitoring and supervising biogas plants.

Replication of a chronic hepatitis B virus genotype F1b construct.

Genotype F is one of the less-studied genotypes of human hepatitis B virus, although it is widely distributed in regions of Central and South American. Our previous studies have shown that HBV genotype F is prevalent in Chile, and phylogenetic analysis of its full-length sequence amplified from the sera of chronically infected patients identified it as HBV subgenotype F1b. We have previously reported the full-length sequence of a HBV molecular clone obtained from a patient chronically infected with genotype F1b. In this report, we established a system to study HBV replication based on hepatoma cell lines transfected with full-length monomers of the HBV genome. Culture supernatants were analyzed after transfection and found to contain both HBsAg and HBeAg viral antigens. Consistently, fractionated cell extracts revealed the presence of viral replication, with both cytoplasmic and nuclear DNA intermediates. Analysis of HBV-transfected cells by indirect immunofluorescence or immunoelectron microscopy revealed the expression of viral antigens and cytoplasmic viral particles, respectively. To test the functionality of the ongoing viral replication further at the level of chromatinized cccDNA, transfected cells were treated with a histone deacetylase inhibitor, and this resulted in increased viral replication. This correlated with changes posttranslational modifications of histones at viral promoters. Thus, the development of this viral replication system for HBV genotype F will facilitate studies on the regulation of viral replication and the identification of new antiviral drugs.