Effects of dietary co-exposure to fungal and herbal functional feed additives on immune parameters and microbial intestinal diversity in rainbow trout (Oncorhynchus mykiss).

Misuse and overuse of antibiotics in aquaculture has proven to be an unsustainable practice leading to increased bacterial resistance. An alternative strategy involves the inclusion of immunostimulants in fish diets, especially fungal and herbal compounds already authorized for human consumption, hence without environmental or public health concerns. In this study, we used a holistic and cross-disciplinary pipeline to assess the immunostimulatory properties of two fungi: Trametes versicolor and Ganoderma lucidum; one herbal supplement, capsaicin in the form of Espelette pepper (Capsicum annuum), and a combination of these fungal and herbal additives on rainbow trout (Oncorhynchus mykiss). We investigated the impact of diet supplementation for 7 weeks on survival, growth performance, cellular, humoral, and molecular immune parameters, as well as the intestinal microbial composition of the fish. Uptake of herbal and fungal compounds influenced the expression of immune related genes, without generating an inflammatory response. Significant differences were detected in the spleen-tlr2 gene expression. Supplementation with herbal additives correlated with structural changes in the fish intestinal microbiota and enhanced overall intestinal microbial diversity. Results demonstrated that the different treatments had no adverse effect on growth performance and survival, suggesting the safety of the different feed additives at the tested concentrations. While the mechanisms and multifactorial interactions remain unclear, this study provides insights not only in regard to nutrition and safety of these compounds, but also how a combined immune and gut microbiota approach can shed light on efficacy of immunostimulant compounds for potential commercial inclusion as feed supplements.

Risk-based Monitoring of Clinical Trials: An Integrative Approach.

PURPOSE: Clinical trial monitoring is an essential component of drug development aimed at safeguarding subject safety, data quality, and protocol compliance by focusing sponsor oversight on the most important aspects of study conduct. In recent years, regulatory agencies, industry consortia, and nonprofit collaborations between industry and regulators, such as TransCelerate and International Committee for Harmonization, have been advocating a new, risk-based approach to monitoring clinical trials that places increased emphasis on critical data and processes and encourages greater use of centralized monitoring. However, how best to implement risk-based monitoring (RBM) remains unclear and subject to wide variations in tools and methodologies. The nonprescriptive nature of the regulatory guidelines, coupled with limitations in software technology, challenges in operationalization, and lack of robust evidence of superior outcomes, have hindered its widespread adoption. METHODS: We describe a holistic solution that combines convenient access to data, advanced analytics, and seamless integration with established technology infrastructure to enable comprehensive assessment and mitigation of risk at the study, site, and subject level. FINDINGS: Using data from completed RBM studies carried out in the last 4 years, we demonstrate that our implementation of RBM improves the efficiency and effectiveness of the clinical oversight process as measured on various quality, timeline, and cost dimensions. IMPLICATIONS: These results provide strong evidence that our RBM methodology can significantly improve the clinical oversight process and do so at a lower cost through more intelligent deployment of monitoring resources to the sites that need the most attention.