Dissecting the metabolic signaling pathways by which microbial molecules drive the differentiation of regulatory B cells.

The host-microbiome axis has been implicated in promoting anti-inflammatory immune responses. Yet, the underlying molecular mechanisms of commensal-mediated IL-10 production by regulatory B cells (Bregs) are not fully elucidated. Here, we demonstrate that bacterial CpG motifs trigger the signaling downstream of TLR9 promoting IκBNS-mediated expression of Blimp-1, a transcription regulator of IL-10. Surprisingly, this effect was counteracted by the NF-κB transcription factor c-Rel. A functional screen for intestinal bacterial species identified the commensal Clostridium sporogenes, secreting high amounts of short-chain fatty acids (SCFAs) and branched-chain fatty acids (BCFAs), as an amplifier of IL-10 production by promoting sustained mTOR signaling in B cells. Consequently, enhanced Breg functionality was achieved by combining CpG with the SCFA butyrate or the BCFA isovalerate thereby synergizing TLR- and mTOR-mediated pathways. Collectively, Bregs required two bacterial signals (butyrate and CpG) to elicit their full suppressive capacity and ameliorate T cell-mediated intestinal inflammation. Our study has dissected the molecular pathways induced by bacterial factors, which might contribute not only to better understanding of host-microbiome interactions, but also to exploration of new strategies for improvement of anti-inflammatory cellular therapy.

Improving Emergency Department Flow: Reducing Turnaround Time for Emergent CT Scans.

Emergency departments across the U.S. are more congested than ever, and there is a pressing need to create capacity by improving patient flow. The long turnaround time of imaging tests, such as computed tomography (CT) scans, are a major reason for delays in treatment and disposition. Over an eight-month pre-intervention period during which 10,063 CT scans were ordered in our emergency department, the average time from a CT order to the availability of the radiologist's final report was 5.9 hours (median=4.2 hours). We created a multi-disciplinary team of physicians, nurses, technicians, transporters, informaticians, and engineers to identify barriers and implement technical as well as human-factors solutions. In the corresponding eight-month period after the implementation of the intervention bundle, there was a 1.2 hour reduction in CT turnaround time, despite a 13.8% increase in the number of CT scans ordered (p<0.0001).