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Background: Mitochondrial diabetes is primarily caused by β-cell failure, a cell type whose unique properties are important in pathogenesis. Methods: By reducing glucose, we induced energetic stress in two rodent β-cell models to assess effects on cellular function. Results: Culturing rat insulin-secreting INS-1 cells in low glucose conditions caused a rapid reduction in whole cell respiration, associated with elevated mitochondrial reactive oxygen species production, and an altered glucose-stimulated insulin secretion profile. Prolonged exposure to reduced glucose directly impaired mitochondrial function and reduced autophagy. Conclusions: Insulinoma cell lines have a very different bioenergetic profile to many other cell lines and provide a useful model of mechanisms affecting β-cell mitochondrial function.

Umbilical cord compression (UCC) sufficient to reduce umbilical blood flow by 30% for 3 days, results in increased fetal plasma cortisol and catecholamines that are likely to promote maturation of the fetal lung and brown adipose tissue (BAT). We determined the effect of UCC on the abundance of uncoupling protein (UCP)1 (BAT only) and -2, glucocorticoid receptor (GR), and 11[beta]-hydroxysteroid dehydrogenase (11[beta]-HSD)1 and -2 mRNA, and mitochondrial protein voltage-dependent anion channel (VDAC) and cytochrome c in these tissues. At 118 [+ or -] 2 days of gestation (dGA; term ~145 days), 14 fetuses were chronically instrumented. Eight fetuses were then subjected to 3 days of UCC from 125 dGA, and the remaining fetuses were sham operated. All fetuses were then exposed to two 1-h episodes of hypoxemia at 130 [+ or -] 1 and 134 [+ or -] 1 dGA before tissue sampling at 137 [+ or -] 2 dGA. In both tissues, UCC upregulated UCP2 and GR mRNA, plus VDAC and cytochrome c mitochondrial proteins. In lung, UCC increased ll[3-HSD1 mRNA but decreased 11[beta]-HSD2 mRNA abundance, a pattern reversed for BAT. UCC increased UCP1 mRNA and its translated protein in BAT. UCP2, GR, 11[beta]-HSD1 and -2 mRNA, plus VDAC and cytochrome c protein abundance were all significantly correlated with fetal plasma cortisol and catecholamine levels, but not thyroid hormone concentrations, in the lung and BAT of UCC fetuses. In conclusion, chronic UCC results in precocious maturation of the fetal lung and BAT mitochondria, an adaptation largely mediated by the surge in fetal plasma cortisol and catecholamines that accompanies UCC. cortisol; catecholamines; mitochondria; proteins

Aim: Pouch–vaginal fistula (PVF) is an uncommon but serious complication of ileo‐anal pouch reconstruction. This study aimed to review the recent management of PVF, in particular the role of anti‐tumour necrosis factor (anti‐TNF) drugs. Method: All patients presenting for management of PVF to our surgical service between 2007 and 2016 were studied. The median duration of follow‐up from diagnosis of PVF was 6 years. Details of the original pouch surgery, timing of presentation of PVF, management and final outcome were recorded. Primary outcome was gastrointestinal (GI) continuity (as defined by the presence or absence of a stoma). Results: A total of 23 patients were identified (median age 45 years) of whom nine had pelvic sepsis at the time of original pouch surgery. Management included local surgical repair, defunctioning ileostomy, pouch excision and anti‐TNF therapy. GI continuity was achieved in 12 patients (52%). Healing of the PVF was achieved in 12 patients (52%). Pelvic sepsis was significantly associated with the need for a long‐term ileostomy (P = 0.009). Biological therapy was used in 12 patients, of whom seven maintained GI continuity. Patients with late presentation PVF (60 months or longer postsurgery) and those with clinical features of Crohn's disease appeared to benefit from anti‐TNF treatment. Conclusion: PVF remains a challenging problem with overall healing rates and GI continuity rates of just over 50%. Anti‐TNF therapy may have a role in patients with late presentation PVF and those with features suggestive of Crohn's disease. [ABSTRACT FROM AUTHOR]

Background : Mitochondrial diabetes is primarily caused by β-cell failure, a cell type whose unique properties are important in pathogenesis. Methods : By reducing glucose, we induced energetic stress in two rodent β-cell models to assess effects on cellular function. Results : Culturing rat insulin-secreting INS-1 cells in low glucose conditions caused a rapid reduction in whole cell respiration, associated with elevated mitochondrial reactive oxygen species production, and an altered glucose-stimulated insulin secretion profile. Prolonged exposure to reduced glucose directly impaired mitochondrial function and reduced autophagy. Conclusions : Insulinoma cell lines have a very different bioenergetic profile to many other cell lines and provide a useful model of mechanisms affecting β-cell mitochondrial function., Competing Interests: Competing interests: JH is an employee of Luxcel Biosciences. None of the other authors have competing interests., (Copyright: © 2019 Morten KJ et al.)

Background : Mitochondrial diabetes is primarily caused by β-cell failure, a cell type whose unique properties are important in pathogenesis. Methods : By reducing glucose, we induced energetic stress in two rodent β-cell models to assess effects on cellular function. Results : Culturing rat insulin-secreting INS-1 cells in low glucose conditions caused a rapid reduction in whole cell respiration, associated with elevated mitochondrial reactive oxygen species production, and an altered glucose-stimulated insulin secretion profile. Prolonged exposure to reduced glucose directly impaired mitochondrial function and reduced autophagy. Conclusions : Insulinoma cell lines have a very different bioenergetic profile to many other cell lines and provide a useful model of mechanisms affecting β-cell mitochondrial function., Competing Interests: Competing interests: JH is an employee of Luxcel Biosciences. None of the other authors have competing interests., (Copyright: © 2017 Morten KJ et al.)

The development of hepatocyte cell models that represent fatty acid partitioning within the human liver would be beneficial for the study of the development and progression of nonalcoholic fatty liver disease (NAFLD). We sought to develop and characterize a novel human liver cell line (LIV0APOLY) to establish a model of lipid accumulation using a physiological mixture of fatty acids under low- and high-glucose conditions. LIV0APOLY cells were compared with a well-established cell line (HepG2) and, where possible, primary human hepatocytes. LIV0APOLY cells were found to proliferate and express some mature liver markers and were wild type for the PNPLA3 (rs738409) gene, whereas HepG2 cells carried the Ile(148)Met variant that is positively associated with liver fat content. Intracellular triglyceride content was higher in HepG2 than in LIV0APOLY cells; exposure to high glucose and/or exogenous fatty acids increased intracellular triglyceride in both cell lines. Triglyceride concentrations in media were higher from LIV0APOLY compared with HepG2 cells. Culturing LIV0APOLY cells in high glucose increased a marker of endoplasmic reticulum stress and attenuated insulin-stimulated Akt phosphorylation whereas low glucose and exogenous fatty acids increased AMPK phosphorylation. Although LIV0APOLY cells and primary hepatocytes stored similar amounts of exogenous fatty acids as triglyceride, more exogenous fatty acids were partitioned toward oxidation in the LIV0APOLY cells than in primary hepatocytes. LIV0APOLY cells offer the potential to be a renewable cellular model for studying the effects of exogenous metabolic substrates on fatty acid partitioning; however, their usefulness as a model of lipoprotein metabolism needs to be further explored., (Copyright © 2015 the American Physiological Society.)

The use of surgical facemasks is ubiquitous in surgical practice. Facemasks have long been thought to confer protection to the patient from wound infection and contamination from the operating surgeon and other members of the surgical staff. More recently, protection of the theatre staff from patient-derived blood/bodily fluid splashes has also been offered as a reason for their continued use. In light of current NHS budget constraints and cost-cutting strategies, we examined the evidence base behind the use of surgical facemasks. Examination of the literature revealed much of the published work on the matter to be quite dated and often studies had poorly elucidated methodologies. As a result, we recommend caution in extrapolating their findings to contemporary surgical practice. However, overall there is a lack of substantial evidence to support claims that facemasks protect either patient or surgeon from infectious contamination. More rigorous contemporary research is needed to make a definitive comment on the effectiveness of surgical facemasks., (© The Royal Society of Medicine.)