Houmann Vinther (damagecolumn95)

This review examines the pathogens, potentially pathogenic microorganisms and ARGs which may be found in animal manure, and evaluates their effect on human health through their exposure to soil and plant resistomes. It takes a broader view than previous studies of this topic, discussing recent data on antibiotic use in farm animals and the effect of these practices on the composition of animal manure; it also examines how fertilization with animal manure may alter soil and crop microbiomes, and proposes the drivers of such changes and their consequences for human health. Having previously demonstrated that tissue miR-375 expression in medullary thyroid carcinoma (MTC) tissues is linked to prognosis, the aim of this study was to assess the diagnostic and prognostic value of circulating miR-375 levels in MTC patients. A series of 68 patients with MTC was retrospectively retrieved and assessed in terms of their clinicopathological characteristics. MiR-375 levels were measured in all patients' presurgical blood samples. Both serum and tissue levels were tested prior to surgery in a subgroup of 57 patients. Serum miR-375 levels were also measured in serum from 49 patients with non-C-cell thyroid nodular diseases (non-CTN), 14 patients with pheochromocytoma, and 19 healthy controls. Circulating miR-375 levels were 101 times higher in the serum of patients with MTC than in all other patients and controls, with no overlap (P < 0.01). No correlation emerged between serum and tissue miR-375 levels. Serum miR-375 levels were higher in MTC patients with N0 than in those with N1 e diagnosis of MTC, with a remarkable specificity. Serum miR-375 also proved a novel marker of prognosis in this disease. Further in vitro experiments to corroborate our results are currently underway.To exclude an excess risk of cardiovascular (CV) events, CV outcomes trials (CVOTs) have assessed the effects of new glucose-lowering therapies, including glucagon-like peptide-1 receptor agonists (GLP-1RAs), in patients with type 2 diabetes and established CV disease or CV risk factors. The CV safety of semaglutide vs. placebo, when added to standard care, was evaluated in the SUSTAIN 6 trial for the formulation administered once-weekly subcutaneously and in PIONEER 6 for the new once-daily oral formulation. In SUSTAIN 6 and PIONEER 6, both powered to demonstrate noninferiority (upper 95% confidence interval [CI] of the hazard ratio [HR] less then 1.8), there were fewer first major adverse CV events with semaglutide vs. placebo, with HRs of 0.74 (95% CI 0.58-0.95) and 0.79 (0.57-1.11), respectively. In SUSTAIN 6, the results were significant for noninferiority and superiority, although the latter was not prespecified. Surprisingly, CV and all-cause mortality were significantly reduced by oral semaglutide in PIONEER 6. The ongoing SOUL CVOT will further inform about CV outcomes with oral semaglutide vs. placebo (NCT03914326). Findings from SUSTAIN 6 and PIONEER 6 fall within the spectrum reported with other GLP-1RA CVOTs noninferiority vs. placebo for major CV events was seen with lixisenatide and exenatide extended-release, while superiority was demonstrated with liraglutide, albiglutide, and dulaglutide. Beneficial outcomes have been recognized in international guidelines, which recommend subcutaneous liraglutide, semaglutide, and dulaglutide to reduce the risk of CV events in high-risk patients. Both indirect mechanisms via risk factor modification and direct effects via GLP-1 receptors in the CV system have been proposed to be responsible for CV event reductions. The exact mechanism(s) remains to be characterized, but appears to be mainly linked to anti-atherosclerotic effects. Further research is needed to elucidate the relevant mechanisms for CV benefits of GLP-1RAs.Glucose effectiveness, defined as the ability of glucose itself to increase glucose utilization and inhibit hepatic glucose production, is an important mechanism ma