Revealing a signaling role of phytosphingosine-1-phosphate in yeast

Perturbing metabolic systems of bioactive sphingolipids with genetic approachMultiple types of “omics” data collected from the systemSystems approach for integrating multiple “omics” informationPredicting signal transduction information flow: lipid; TF activation; gene expressio

The Global Health System: Linking Knowledge with Action—Learning from Malaria

In the third in a series of articles on the changing nature of global health institutions, Gerald Keusch and colleagues examine institutional arrangements for malaria research

The effect of adding goal-directed hemodynamic management for elective patients in an established enhanced recovery program for colorectal surgery: results of quasi-experimental pragmatic trial

BACKGROUND: Recent literature has demonstrated that hemodynamic instability in the intraoperative period places patients at risk of poor outcomes. Furthermore, recent studies have reported that stroke volume optimization and protocolized hemodynamic management may improve perioperative outcomes, especially surgical site infection (SSI), in certain high-risk populations. However, the optimal strategy for intraoperative management of all elective patients within an enhanced recovery program remains to be elucidated. METHODS: We performed a pre-post quasi-experimental study to assess the effect of adding goal-directed hemodynamic therapy to an enhanced recovery program (ERP) for colorectal surgery on SSI and other outcomes. Three groups were compared: "Pre-ERP," defined as historical control (before enhanced recovery program); "ERP," defined as enhanced recovery program using zero fluid balance; and "ERP+GDHT," defined as enhanced recovery program plus goal-directed hemodynamic therapy. Outcomes were obtained through our National Surgical Quality Improvement Program participation. RESULTS: A total of 623 patients were included in the final analysis (Pre-ERP = 246, ERP = 140, and ERP + GDHT = 237). Demographics and baseline clinical characteristics were balanced between groups. We did not observe statistically significant differences in SSI or composite complication rates in unadjusted or adjusted analysis. There was no evidence of association between study group and 30-day readmission. American Society of Anesthesiologists status ≥ 3 and open surgical approach were significantly associated with increased risk of SSI, composite complication, and 30-day readmission (p < 0.05 for all) in all groups. CONCLUSIONS: There was no evidence that addition of goal-directed hemodynamic therapy for all patients in an enhanced recovery program for colorectal surgery affects the risk of SSI, composite complications, or 30-day readmission. Further research is needed to investigate whether there is benefit of goal-directed hemodynamic therapy for select high-risk populations. TRIAL REGISTRATION: NCT03189550. Registered 16 June 2017-Retrospectively registered, https://www.clinicaltrials.gov/ct2/results?cond=&term=NCT03189550&cntry=&state=&city=&dist=

Organs-on-Chips as Bridges for Predictive Toxicology

The next generation of chemical toxicity testing will use organs-on-chips (OoCs)—3D cultures of heterotypic cells with appropriate extracellular matrices to better approximate the in vivo cellular microenvironment. Researchers are already working to validate whether OoCs are predictive of toxicity in humans. Here, we review two other key aspects of how OoCs may advance predictive toxicology—each taking advantage of OoCs as systems of intermediate complexity that remain experimentally accessible. First, the intermediate complexity of OoCs will help elucidate the scale(s) of organismal complexity that currently confound computational predictions of in vivo toxicity from in vitro data sets. Identifying the strongest confounding factors will help researchers improve the computational models underlying such predictions. Second, the experimental accessibility of OoCs will allow researchers to analyze chemical-exposure responses in OoCs using an array of high-content readouts—from fluorescent biosensors that report dynamic changes in specific cell signaling pathways to unbiased searches over broader biochemical space using technologies like ion mobility-mass spectrometry. Such high-content information on OoC responses will help determine the details of adverse outcome pathways. We note these possible uses of OoCs so that researchers and engineers can consider them in the design of next-generation OoC control, perfusion, and analysis platforms