Search

Background: Non-alcoholic fatty liver disease (NAFLD) may be associated with changes in bile acid (BA) metabolism. Hepatic BA production, measured by serum levels of the precursor 7α-hydroxy-4-cholesten-3-one (C4), is regulated by the farnesoid-X-receptor (FXR)-dependent ileal hormone fibroblast growth factor 19 (FGF19). Low FGF19 and high C4 are features of chronic BA diarrhea. Obeticholic acid, an FXR agonist, stimulates FGF19 and has shown therapeutic potential in both BA diarrhea and in NAFLD. We hypothesized there are associations of FGF19, C4 and BA diarrhea with NAFLD., Methods and Findings: 127 patients with known NAFLD were recruited prospectively. Clinical features, including metformin use, markers of NAFLD severity and BA synthesis were analyzed. The overall incidence of chronic diarrhea was 25%, with features of BA diarrhea in 12%. FGF19 negatively correlated with C4 (rs = -0.43, p = 0.001) and with alanine aminotransferase (rs = -0.22, p = 0.03), but not with either NAFLD fibrosis or Fibroscan scores. High C4 was associated with a higher NAFLD fibrosis score (p < 0.05), and with diarrhea (p = 0.001). The median NAFLD fibrosis score was higher in those with diarrhea (p = 0.002). Metformin use, in 44% overall, was particularly associated with diarrhea (in 36% vs 17%, p = 0.02), and a lower median FGF19 (74 vs 105 pg/mL, p < 0.05)., Conclusions: Increased hepatic BA production and diarrhea, but not low FGF19, were associated with increased NAFLD fibrosis score, indicating dysregulation of the FXR-FGF19 axis and suggesting hepatic FGF19 resistance. Metformin use was an important factor in a subgroup, lowering FGF19, and resulting in bile acid diarrhea., Competing Interests: We have read the journal's policy and the authors of this manuscript have the following competing interests: JW has been a consultant, speaker or advisory board member for Intercept Pharmaceuticals, GE Healthcare, Novartis, Albireo, Falk, Enyo and Metacrine. Funding for this study was received in the form of an institutional award to support RA from a Intercept Pharmaceuticals. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Antibiotic misuse and overuse in both the healthcare and agricultural fields have dramatically increased the prevalence of antibiotic resistance in human pathogens. Two strains of methicillin-resistant Staphylococcus aureus (MRSA) (ATCC 43330 and a wild-type) and 1 strain of methicillin-susceptible S. aureus (ATCC 25923) were challenged (9 runs in triplicate) in a preliminary study with ultraviolet germicidal irradiation (UVGI) doses ranging from 0.25 to 3.00 mJ/cm(2). The mean percent kill was calculated for each strain when compared with the control plates (no exposure to UVGI). Then, each strain was challenged (22 runs in triplicate) with UVGI doses of 2.00, 2.50, and 3.00 mJ/cm(2). The results suggest a difference between the doses required to disinfect surfaces with each strain. Assuming a standard error rate of α = 0.05, there was a significant difference in variance between the MRSA (ATCC 43330 and wild type) strains and the S. aureus (ATCC 25923) methicillin-susceptible strain.

Blood loss during orthopaedic procedures can be extensive and the need for allogeneic blood is a common requirement. However, blood transfusion conceals a number of well-recognised risks and complications and blood products have become more expensive because of their specific preparation procedure. Surgical technique, awareness of the problem and restriction of transfusion triggers are important factors affecting the management of blood loss. Several studies have additionally shown the efficacy of epoetin injections in increasing the pre-operative haemoglobin level. On the other hand, the true benefit of pre-operative autologous donation, acute normovolemic haemodilution and COX-2 selective NSAIDs remains under dispute. Regarding the role of platelet rich plasmapheresis, fibrin sealing and anti-fibinolytic drugs more data are needed. Hypotensive epidural anaesthesia seems to be an advantageous method in minimising peri-operative blood loss. However, this is not a widely performed technique in orthopaedic surgery. In addition, post-operative blood cell saving systems after total knee or hip arthroplasty have been reported to significantly minimise allogeneic blood transfusions when compared to control groups. It can be concluded that many interventions diminish more or less allogeneic blood transfusion in elective orthopaedic surgery. Nevertheless more prospective studies are needed and appropriate algorithms should be applied in peri-operative blood loss management. This review presents an overview of the available interventions which aim to diminish the use of allogeneic blood in elective orthopaedic surgery.