Can hospital audit teams identify case management problems, analyse their causes, identify and implement improvements? A cross-sectional process evaluation of obstetric near-miss case reviews in Benin.

BACKGROUND: Obstetric near-miss case reviews are being promoted as a quality assurance intervention suitable for hospitals in low income countries. We introduced such reviews in five district, regional and national hospitals in Benin, West Africa. In a cross-sectional study we analysed the extent to which the hospital audit teams were able to identify case management problems (CMPs), analyse their causes, agree on solutions and put these solutions into practice. METHODS: We analysed case summaries, women's interview transcripts and audit minutes produced by the audit teams for 67 meetings concerning one woman with near-miss complications each. We compared the proportion of CMPs identified by an external assessment team to the number found by the audit teams. For the latter, we described the CMP causes identified, solutions proposed and implemented by the audit teams. RESULTS: Audit meetings were conducted regularly and were well attended. Audit teams identified half of the 714 CMPs; they were more likely to find managerial ones (71%) than the ones relating to treatment (30%). Most identified CMPs were valid. Almost all causes of CMPs were plausible, but often too superficial to be of great value for directing remedial action. Audit teams suggested solutions, most of them promising ones, for 38% of the CMPs they had identified, but recorded their implementation only for a minority (8.5%). CONCLUSIONS: The importance of following-up and documenting the implementation of solutions should be stressed in future audit interventions. Tools facilitating the follow-up should be made available. Near-miss case reviews hold promise, but their effectiveness to improve the quality of care sustainably and on a large scale still needs to be established

Enhancing liver mitochondrial fatty acid oxidation capacity in obese mice improves insulin sensitivity independently of hepatic steatosis

International audienc

Maintenance of red blood cell integrity by AMP-activated protein kinase α1 catalytic subunit

AMP-activated protein kinase (AMPK) plays a pivotal role in regulating cellular energy metabolism. We previously showed that AMPKα1-/- mice develop moderate anemia associated with splenomegaly and high reticulocytosis. Here, we report that splenectomy of AMPKα1-/- mice worsened anemia supporting evidence that AMPKα1-/- mice developed a compensatory response through extramedullary erythropoiesis in the spleen. Transplantation of bone marrow from AMPKα1-/- mice into wild-type recipients recapitulated the hematologic phenotype. Further, AMPKα1-/- red blood cells (RBC) showed less deformability in response to shear stress limiting their membrane flexibility. Thus, our results highlight the crucial role of AMPK to preserve RBC integrity. © 2010 Federation of European Biochemical Societies.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

The MODY1 Gene for Hepatocyte Nuclear Factor 4α and a Feedback Loop Control COUP-TFII Expression in Pancreatic Beta Cells▿

Pancreatic islet beta cell differentiation and function are dependent upon a group of transcription factors that maintain the expression of key genes and suppress others. Knockout mice with the heterozygous deletion of the gene for chicken ovalbumin upstream promoter-transcription factor II (COUP-TFII) or the complete disruption of the gene for hepatocyte nuclear factor 4α (HNF4α) in pancreatic beta cells have similar insulin secretion defects, leading us to hypothesize that there is transcriptional cross talk between these two nuclear receptors. Here, we demonstrate specific HNF4α activation of a reporter plasmid containing the COUP-TFII gene promoter region in transfected pancreatic beta cells. The stable association of the endogenous HNF4α with a region of the COUP-TFII gene promoter that contains a direct repeat 1 (DR-1) binding site was revealed by chromatin immunoprecipitation. Mutation experiments showed that this DR-1 site is essential for HNF4α transactivation of COUP-TFII. The dominant negative suppression of HNF4α function decreased endogenous COUP-TFII expression, and the specific inactivation of COUP-TFII by small interfering RNA caused HNF4α mRNA levels in 832/13 INS-1 cells to decrease. This positive regulation of HNF4α by COUP-TFII was confirmed by the adenovirus-mediated overexpression of human COUP-TFII (hCOUP-TFII), which increased HNF4α mRNA levels in 832/13 INS-1 cells and in mouse pancreatic islets. Finally, hCOUP-TFII overexpression showed that there is direct COUP-TFII autorepression, as COUP-TFII occupies the proximal DR-1 binding site of its own gene in vivo. Therefore, COUP-TFII may contribute to the control of insulin secretion through the complex HNF4α/maturity-onset diabetes of the young 1 (MODY1) transcription factor network operating in beta cells

The Transcription Factor COUP-TFII Is Negatively Regulated by Insulin and Glucose via Foxo1- and ChREBP-Controlled Pathways▿

COUP-TFII has an important role in regulating metabolism in vivo. We showed this previously by deleting COUP-TFII from pancreatic beta cells in heterozygous mutant mice, which led to abnormal insulin secretion. Here, we report that COUP-TFII expression is reduced in the pancreas and liver of mice refed with a carbohydrate-rich diet and in the pancreas and liver of hyperinsulinemic and hyperglycemic mice. In pancreatic beta cells, COUP-TFII gene expression is repressed by secreted insulin in response to glucose through Foxo1 signaling. Ex vivo COUP-TFII reduces insulin production and secretion. Our results suggest that beta cell insulin secretion is under the control of an autocrine positive feedback loop by alleviating COUP-TFII repression. In hepatocytes, both insulin, through Foxo1, and high glucose concentrations repress COUP-TFII expression. We demonstrate that this negative glucose effect involves ChREBP expression. We propose that COUP-TFII acts in a coordinate fashion to control insulin secretion and glucose metabolism

Insulin resistance per se drives early and reversible dysbiosis-mediated gut barrier impairment and bactericidal dysfunction

International audienceA common feature of metabolic diseases is their association with chronic low-grade inflammation. While enhanced gut permeability and systemic bacterial endotoxin translocation have been suggested as key players of this metaflammation, the mechanistic bases underlying these features upon the diabesity cascade remain partly understood. Here, we show in mice that, independently of obesity, the induction of acute and global insulin resistance and associated hyperglycemia, upon treatment with an insulin receptor (IR) antagonist (S961), elicit gut hyperpermeability without triggering systemic inflammatory response. Of note, S961-treated diabetic mice display major defects of gut barrier epithelial functions, such as increased epithelial paracellular permeability and impaired cell-cell junction integrity. We also observed in these mice the early onset of a severe gut dysbiosis, as characterized by the bloom of pro-inflammatory Proteobacteria, and the later collapse of Paneth cells antimicrobial defense. Interestingly, S961 treatment discontinuation is sufficient to promptly restore both the gut microbial balance and the intestinal barrier integrity. Moreover, fecal transplant approaches further confirm that S961-mediated dybiosis contributes at least partly to the disruption of the gut selective epithelial permeability upon diabetic states. Together, our results highlight that insulin signaling is an indispensable gatekeeper of intestinal barrier integrity, acting as a safeguard against microbial imbalance and acute infections by enteropathogens

Novel Grb14-Mediated Cross Talk between Insulin and p62/Nrf2 Pathways Regulates Liver Lipogenesis and Selective Insulin Resistance

International audienc