Natural feed after weaning improves the reproductive status of Solea senegalensis breeders

The aim of this study was to evaluate the effect of long term natural feeding in the subsequent reproductive status of 4 years old cultured Solea senegalensis, and to determine if the potential changes were structural or feeding dependent. To this aim, two different feeding regimes were used from one year after weaning and during the following 3 years; 1) a commercial dry food diet and 2) a natural feeding regime. After this period, the proportion of fluent males and the evolution of maturity stages of females over a breeding season were studied. A complete sperm quality analysis assessment was carried out, including individual volumes, motility, density and curvilinear, rectilinear and mean velocities of spermatozoa. Moreover, viability and apoptosis indexes were analyzed as indicator of molecular sperm membrane integrity. Additionally, a morphological characterization of the testes during the spawning season was conducted. Finally, both groups were fed with the same commercial pellets during one year to evaluate the effect of the diet of previous years on sperm quality. The results of this study showed how feeding can improve not only sperm quality and quantity, but also the proportion of fluent males and females in advanced maturity stages. All the sperm quality parameters resulted significantly higher in the group fed with a natural diet. Moreover, the number of apoptotic cells was significantly higher in the group fed with a commercial diet. According to the morphological features of the testes, the animals fed with a natural diet presented more basal position, less protuberances and irregular edges when compared with the animals fed with commercial diet. Interestingly, the progression of the spermatogenesis determined by the proportion of germ cells and the production of spermatozoa determined by the wider of the ducts system was also significantly larger in the natural diet group. After the standardization of the diets, mean volume per male and production of total motile cells were sig- nificantly higher in the group that was previously fed a natural diet, confirming structural improvements.Versión del editor2,04

Comprehensive analysis and insights gained from long-term experience of the Spanish DILI Registry

Background & aims: Prospective drug-induced liver injury (DILI) registries are important sources of information on idiosyncratic DILI. We aimed to present a comprehensive analysis of 843 patients with DILI enrolled into the Spanish DILI Registry over a 20-year time period. Methods: Cases were identified, diagnosed and followed prospectively. Clinical features, drug information and outcome data were collected. Results: A total of 843 patients, with a mean age of 54 years (48% females), were enrolled up to 2018. Hepatocellular injury was associated with younger age (adjusted odds ratio [aOR] per year 0.983; 95% CI 0.974-0.991) and lower platelet count (aOR per unit 0.996; 95% CI 0.994-0.998). Anti-infectives were the most common causative drug class (40%). Liver-related mortality was more frequent in patients with hepatocellular damage aged ≥65 years (p = 0.0083) and in patients with underlying liver disease (p = 0.0221). Independent predictors of liver-related death/transplantation included nR-based hepatocellular injury, female sex, higher onset aspartate aminotransferase (AST) and bilirubin values. nR-based hepatocellular injury was not associated with 6-month overall mortality, for which comorbidity burden played a more important role. The prognostic capacity of Hy's law varied between causative agents. Empirical therapy (corticosteroids, ursodeoxycholic acid and MARS) was prescribed to 20% of patients. Drug-induced autoimmune hepatitis patients (26 cases) were mainly females (62%) with hepatocellular damage (92%), who more frequently received immunosuppressive therapy (58%).The present study has been supported by grants of Instituto de Salud Carlos III cofounded by Fondo Europeo de Desarrollo Regional – FEDER (contract numbers: PI19/00883, PI16/01748, PI18/00901, PI18/01804, PI-0285-2016, PI-0274-2016, PI-0310- 2018, PT17/0017/0020) and Agencia Española del Medicamento. CIBERehd and Plataforma ISCIII Ensayos Clinicos are funded by Instituto de Salud Carlos III. MRD holds a Joan Rodes (JR16/ 00015)/Acción B clinicos investigadores (B-0002-2019) and JSC a Rio Hortega (CM17/00243) research contract from ISCIII and Consejería de Salud de Andalucía. The funding sources had no involvement in the study design; in the collection, analysis, and interpretation of data; in the writing of the report or in the de- cision to submit the manuscript for publication

Association between convalescent plasma treatment and mortality in COVID-19: a collaborative systematic review and meta-analysis of randomized clinical trials.

Funder: laura and john arnold foundationBACKGROUND: Convalescent plasma has been widely used to treat COVID-19 and is under investigation in numerous randomized clinical trials, but results are publicly available only for a small number of trials. The objective of this study was to assess the benefits of convalescent plasma treatment compared to placebo or no treatment and all-cause mortality in patients with COVID-19, using data from all available randomized clinical trials, including unpublished and ongoing trials (Open Science Framework, https://doi.org/10.17605/OSF.IO/GEHFX ). METHODS: In this collaborative systematic review and meta-analysis, clinical trial registries (ClinicalTrials.gov, WHO International Clinical Trials Registry Platform), the Cochrane COVID-19 register, the LOVE database, and PubMed were searched until April 8, 2021. Investigators of trials registered by March 1, 2021, without published results were contacted via email. Eligible were ongoing, discontinued and completed randomized clinical trials that compared convalescent plasma with placebo or no treatment in COVID-19 patients, regardless of setting or treatment schedule. Aggregated mortality data were extracted from publications or provided by investigators of unpublished trials and combined using the Hartung-Knapp-Sidik-Jonkman random effects model. We investigated the contribution of unpublished trials to the overall evidence. RESULTS: A total of 16,477 patients were included in 33 trials (20 unpublished with 3190 patients, 13 published with 13,287 patients). 32 trials enrolled only hospitalized patients (including 3 with only intensive care unit patients). Risk of bias was low for 29/33 trials. Of 8495 patients who received convalescent plasma, 1997 died (23%), and of 7982 control patients, 1952 died (24%). The combined risk ratio for all-cause mortality was 0.97 (95% confidence interval: 0.92; 1.02) with between-study heterogeneity not beyond chance (I2 = 0%). The RECOVERY trial had 69.8% and the unpublished evidence 25.3% of the weight in the meta-analysis. CONCLUSIONS: Convalescent plasma treatment of patients with COVID-19 did not reduce all-cause mortality. These results provide strong evidence that convalescent plasma treatment for patients with COVID-19 should not be used outside of randomized trials. Evidence synthesis from collaborations among trial investigators can inform both evidence generation and evidence application in patient care

Association between polymorphisms in sex hormones synthesis and metabolism and prostate cancer aggressiveness

<div><p>Novel biomarkers for prostate cancer (PCa) diagnosis and prognosis are necessary to improve the accuracy of current ones employed in clinic. We performed a retrospective study between the association of several polymorphisms in the main genes involved in the synthesis and metabolism of sex hormones and PCa risk and aggressiveness. A total of 311 Caucasian men (155 controls and 156 patients) were genotyped for 9 SNPs in <i>AR</i>, <i>CYP17A1</i>, <i>LHCGR</i>, <i>ESR1</i> and <i>ESR2</i> genes. Diagnostic PSA serum levels, Gleason score, tumor stage, D´Amico risk and data of clinical progression were obtained for patients at the moment of the diagnosis and after 54 months of follow-up. Chi-squared test were used for comparisons between clinical variables groups, logistic regression for clinical variables associations between SNPs; and Kaplan–Meier for the association between SNPs and time to biochemical progression. We found 5 variants (<i>CYP17A</i>1) rs743572, rs6162, rs6163; (<i>LHCGR</i>) rs2293275 and (<i>ESR2</i>) rs1256049 that were statistically significant according to clinical variables (PSA, D´Amico risk and T stage) on a case-case analysis. Moreover, the presence of </p><p><i>A</i></p> and <p><i>G</i></p> alleles in rs743572 and rs6162 respectively, increase the risk of higher PSA levels (>10 ng/μl). With respect to D´Amico risk rs743572 (<p><i>AG-GG</i></p>), rs6162 (<p><i>AG-AA</i></p>) and rs6163 (<p><i>AC-AA</i></p>) were associated with an increased risk; and last, <p><i>AC</i></p> and <p><i>AA</i></p> genotypes for rs6163 were associated with a shorter biochemical recurrence free survival (BRFS) in patients with radical prostatectomy. In multigene analysis, several variants in SNPs rs2293275, rs6152, rs1062577, rs6162, rs6163, rs1256049 and rs1004467 were described to be associated with a more aggressiveness in patients. However, none of the selected SNPs show significant values between patients and controls. In conclusion, this study identified inherited variants in genes <i>CYP17A1</i>, <i>LHCGR</i> and <i>ESR2</i> related to more aggressiveness and/or a poor progression of the disease. According to this study, new promise PCa biomarkers for clinical management could be included in these previous SNPs.<p></p></div

Genotyping and Allelic Proportion of SNPs.

<p>Genotyping and Allelic Proportion of SNPs.</p

Summary of clinical variables.

<p>Summary of clinical variables.</p

BRFS according rs6163 (<i>CYP17A1</i>) genotype.

<p>Kaplan-Meier curves of time to biochemical recurrence in patients treated with radical prostatectomy and stratified by rs6163 genotype (<i>CC vs</i>. </p><p><i>AC+AA</i></p>). P value obtained from log-rank t test.<p></p

Significant associations between clinical variables and SNPs in PCa patients.

<p>Significant associations between clinical variables and SNPs in PCa patients.</p

Multivariate analysis for differentially distributed SNPs and clinical variables.

<p>Multivariate analysis for differentially distributed SNPs and clinical variables.</p