Culturing Human Gut Microbiomes in the Laboratory.

The human gut microbiota is a complex community of prokaryotic and eukaryotic microbes and viral particles that is increasingly associated with many aspects of host physiology and health. However, the classical microbiology approach of axenic culture cannot provide a complete picture of the complex interactions between microbes and their hosts in vivo. As such, recently there has been much interest in the culture of gut microbial ecosystems in the laboratory as a strategy to better understand their compositions and functions. In this review, we discuss the model platforms and methods available in the contemporary microbiology laboratory to study human gut microbiomes, as well as current knowledge surrounding the isolation of human gut microbes for the potential construction of defined communities for use in model systems.

Multicenter study of acetaminophen hepatotoxicity reveals the importance of biological endpoints in genomic analyses.

Gene expression profiling is a widely used technique with data from the majority of published microarray studies being publicly available. These data are being used for meta-analyses and in silico discovery; however, the comparability of toxicogenomic data generated in multiple laboratories has not been critically evaluated. Using the power of prospective multilaboratory investigations, seven centers individually conducted a common toxicogenomics experiment designed to advance understanding of molecular pathways perturbed in liver by an acute toxic dose of N-acetyl-p-aminophenol (APAP) and to uncover reproducible genomic signatures of APAP-induced toxicity. The nonhepatotoxic APAP isomer N-acetyl-m-aminophenol was used to identify gene expression changes unique to APAP. Our data show that c-Myc is induced by APAP and that c-Myc-centered interactomes are the most significant networks of proteins associated with liver injury. Furthermore, sources of error and data variability among Centers and methods to accommodate this variability were identified by coupling gene expression with extensive toxicological evaluation of the toxic responses. We show that phenotypic anchoring of gene expression data is required for biologically meaningful analysis of toxicogenomic experiments.

Database design to ensure anonymous study of medical errors: a report from the ASIPS Collaborative.

Medical error reporting systems are important information sources for designing strategies to improve the safety of health care. Applied Strategies for Improving Patient Safety (ASIPS) is a multi-institutional, practice-based research project that collects and analyzes data on primary care medical errors and develops interventions to reduce error. The voluntary ASIPS Patient Safety Reporting System captures anonymous and confidential reports of medical errors. Confidential reports, which are quickly de-identified, provide better detail than do anonymous reports; however, concerns exist about the confidentiality of those reports should the database be subject to legal discovery or other security breaches. Standard database elements, for example, serial ID numbers, date/time stamps, and backups, could enable an outsider to link an ASIPS report to a specific medical error. The authors present the design and implementation of a database and administrative system that reduce this risk, facilitate research, and maintain near anonymity of the events, practices, and clinicians.