Glucose-fed microbiota alters C. elegans intestinal epithelium and increases susceptibility to multiple bacterial pathogens.

Overconsumption of dietary sugar can lead to many negative health effects including the development of Type 2 diabetes, metabolic syndrome, cardiovascular disease, and neurodegenerative disorders. Recently, the human intestinal microbiota, strongly associated with our overall health, has also been known to be affected by diet. However, mechanistic insight into the importance of the human intestinal microbiota and the effects of chronic sugar ingestion has not been possible largely due to the complexity of the human microbiome which contains hundreds of types of organisms. Here, we use an interspecies C. elegans/E. coli system, where E. coli are subjected to high sugar, then consumed by the bacterivore host C. elegans to become the microbiota. This glucose-fed microbiota results in a significant lifespan reduction accompanied by reduced healthspan (locomotion), reduced stress resistance, and changes in behavior and feeding. Lifespan reduction is also accompanied by two potential major contributors: increased intestinal bacterial density and increased concentration of reactive oxygen species. The glucose-fed microbiota accelerated the age-related development of intestinal cell permeability, intestinal distention, and dysregulation of immune effectors. Ultimately, the changes in the intestinal epithelium due to aging with the glucose-fed microbiota results in increased susceptibility to multiple bacterial pathogens. Taken together, our data reveal that chronic ingestion of sugar, such as a Western diet, has profound health effects on the host due to changes in the microbiota and may contribute to the current increased incidence of ailments including inflammatory bowel diseases as well as multiple age-related diseases.

Using Organizational Philosophy to Create a Self-Sustaining Compensation Plan Without Harming Academic Missions.

PROBLEM: Academic physician reimbursement has moved to productivity-based compensation plans. To be sustainable, such plans must be self-funding. Additionally, unless research and education are appropriately valued, faculty involved in these efforts will become disillusioned, yet revenue generation in these activities is less robust than for clinical care activities. APPROACH: Faculty at the Department of Medicine, University of Florida Health, elected a committee of junior and senior faculty and division chiefs to restructure the compensation plan in fiscal year (FY) 2011. This committee was charged with designing a new compensation plan based on seven principles of organizational philosophy: equity, compensation coupled to productivity, authority aligned with responsibility, respect for all academic missions, transparency, professionalism, and self-funding in each academic mission. OUTCOMES: The new compensation plan was implemented in FY2013. A survey administered at the end of FY2015 showed that 61% (76/125) of faculty were more satisfied with this plan than the previous plan. Since the year before implementation, clinical relative value units per faculty increased 7% (from 3,458 in FY2012 to 3,704 in FY2015, P < .002), incentives paid per faculty increased 250% (from $3,191 in FY2012 to $11,153 in FY2015, P ≤ .001), and publications per faculty increased 15% (from 2.6 in FY2012 to 3.0 in FY2015, P < .001). Grant submissions, external funding, and teaching hours also increased per faculty but did not reach statistical significance. NEXT STEPS: An important next step will be to incorporate quality metrics into the compensation plan, without affecting costs or throughput.

Thrombin generation using the calibrated automated thrombinoscope to assess reversibility of dabigatran and rivaroxaban.

The new direct-acting anticoagulants such as dabigatran and rivaroxaban are usually not monitored but may be associated with haemorrhage, particularly where renal impairment occurs. They have no effective "antidotes". We studied 17 patients receiving dabigatran 150 mg twice daily for non-valvular atrial fibrillation and 15 patients receiving rivaroxaban 10 mg daily for the prevention of deep venous thrombosis after hip or knee replacement surgery. We assessed the effect of these drugs on commonly used laboratory tests and Calibrated Automated Thrombogram (CAT) using plasma samples. We also assessed effects in fresh whole blood citrated patient samples using thromboelastography on the TEG and the ROTEM. The efficacy of nonspecific haemostatic agents prothrombin complex concentrate (PCC), Factor VIII Inhibitor By-passing Activity (FEIBA) and recombinant activated factor VII (rVIIa) were tested by reversal of abnormal thrombin generation using the CAT. Concentrations added ex vivo were chosen to reflect doses normally given in vivo. Dabigatran significantly increased the dynamic parameters of the TEG and ROTEM and the lag time of the CAT. It significantly reduced the endogenous thrombin potential (ETP) and reduced the peak height of the CAT. Rivaroxaban did not affect the TEG and ROTEM parameters but did increase the lag time and reduce ETP and peak height of the CAT. For both drugs, these parameters were significantly and meaningfully corrected by PCC and FEIBA and to a lesser but still significant extent by rFVIIa. These results may be useful in devising a reversal strategy in patients but clinical experience will be needed to verify them.