The incidence of chronic liver disease is constantly increasing, owing to the obesity epidemic. However, the causes and mechanisms of inflammation-mediated liver damage remain poorly understood. ...Endoplasmic reticulum (ER) stress is an initiator of cell death and inflammatory mechanisms. Although obesity induces ER stress, the interplay between hepatic ER stress, NLRP3 inflammasome activation and hepatocyte death signaling has not yet been explored during the etiology of chronic liver diseases. Steatosis is a common disorder affecting obese patients; moreover, 25% of these patients develop steatohepatitis with an inherent risk for progression to hepatocarcinoma. Increased plasma LPS levels have been detected in the serum of patients with steatohepatitis. We hypothesized that, as a consequence of increased plasma LPS, ER stress could be induced and lead to NLRP3 inflammasome activation and hepatocyte death associated with steatohepatitis progression. In livers from obese mice, administration of LPS or tunicamycin results in IRE1α and PERK activation, leading to the overexpression of CHOP. This, in turn, activates the NLRP3 inflammasome, subsequently initiating hepatocyte pyroptosis (caspase-1, -11, interleukin-1β secretion) and apoptosis (caspase-3, BH3-only proteins). In contrast, the LPS challenge is blocked by the ER stress inhibitor TUDCA, resulting in: CHOP downregulation, reduced caspase-1, caspase-11, caspase-3 activities, lowered interleukin-1β secretion and rescue from cell death. The central role of CHOP in mediating the activation of proinflammatory caspases and cell death was characterized by performing knockdown experiments in primary mouse hepatocytes. Finally, the analysis of human steatohepatitis liver biopsies showed a correlation between the upregulation of inflammasome and ER stress markers, as well as liver injury. We demonstrate here that ER stress leads to hepatic NLRP3 inflammasome pyroptotic death, thus contributing as a novel mechanism of inflammation-mediated liver injury in chronic liver diseases. Inhibition of ER-dependent inflammasome activation and cell death pathways may represent a potential therapeutic approach in chronic liver diseases.
Background: revisional bariatric surgery is gaining increasing interest as long term follow-up studies demonstrate an elevated failure rate of primary surgery due to insufficient weight loss, weight ...regain or complications. This particularly concerns restrictive bariatric surgery which has been widely adopted from the ‘80s till present through different procedures, notably vertical banded gastroplasty, laparoscopic adjusted gastric banding and sleeve gastrectomy. The aim of this study is to define which revisional bariatric procedure performs the best after failure of primary restrictive surgery.
Methods: a systematic review and network meta-analysis of 39 studies was conducted following the PRISMA guidelines and the Cochrane protocol.
Results: biliopancreatic diversion with duodenal switch guarantees the best results in terms of weight loss (1 and 3-years %TWL MD: 12.38 and 28.42) followed by single-anastomosis duodenoileal bypass (9.24 and 19.13), one-anastomosis gastric bypass (7.16 and 13.1), and Roux-en-Y gastric bypass (4.68 and 7.3) compared to re-sleeve gastrectomy. Duodenal switch and Roux-en-Y gastric bypass are associated to an increased risk of late major morbidity (OR: 3.07 and 2.11 respectively) compared to re-sleeve gastrectomy while no significant difference was highlighted for the other procedures. Re-sleeve gastrectomy is the revisional intervention most frequently burdened by weight recidivism; compared to it, patients undergoing single-anastomosis duodenoileal bypass have the lowest risk of weight regain (OR: 0.07).
Conclusion: considering the analyzed outcomes altogether, single-anastomosis duodenoileal bypass and one-anastomosis gastric bypass are the most performing revisional procedures after failure of restrictive surgery due to satisfying short and mid-term weight loss and low early and late morbidity. Moreover, single-anastomosis duodenoileal bypass has low risk of weight recidivism.
•The first Network Meta-analysis exploring outcomes of revisional bariatric surgery.•Sleeve gastrectomy is the worst procedure for weight loss and risk of weight regain while Roux-en-Y gastric bypass has limited weight loss benefits and moderate morbidity.•Biliopancreatic diversion with duodenal switch guarantees the best short- and mid-term weight loss with elevated morbidity.•Single-anastomosis duodeno-ileal bypass and one-anastomosis gastric bypass determine satisfying weight loss with low morbidity.•Single-anastomosis duodeno-ileal bypass is associated with the lowest risk of weight regain.
•Elevated CO2 did not affect the ability of L. minor plants to accumulate Cd in their tissues.•Elevated CO2 decreased Cd toxicity in L. minor plants by increasing photosynthesis.•Elevated CO2 reduced ...Cd toxicity in duckweed by enhancing antioxidant system.
The objective of this study was to investigate the combined effects of elevated CO2 and cadmium (Cd) treatments on growth, photosynthetic efficiency and phytoremediation ability in Lemna minor L. Plants of L. minor were exposed to different Cd concentrations (0, 1.5, 2.5 and 5mgL−1 Cd) for periods of 24, 48 and 72h at ambient (AC) and at elevated (EC) CO2 (350 and 700ppm, respectively). Cadmium concentration, bioconcentration factor, enzyme activities and thiols content enhanced in plants with the increase of Cd treatments, time of exposure and at both CO2 levels. Glutathione levels increased only at AC. Growth, photosynthetic and chlorophyll fluorescence parameters, and the reduced glutathione to oxidized glutathione ratio declined in plants with increasing exposure time, Cd treatments and at both CO2 levels. Our results suggested that the alleviation of toxicity, at low Cd doses, observed in L. minor grown at EC is dependent on both increased photosynthesis and an enhanced antioxidant capacity.
We investigated how the presence of cadmium (Cd) at the emergence of Phragmites australis Trin. (Cav.) ex Steudel plants from rhizomes interacted with leaf and chloroplast physiological and ...biochemical processes. About 8.5 nmol Cd mg(-1) chlorophyll was found in leaves, and 0.83 nmol Cd mg(-1) chlorophyll was found in chloroplasts of plants treated with 50 micromolar Cd. As a result, a 30% loss of chlorophyll was measured concomitantly with a comparable percentage reduction in light-saturated photosynthesis. Rubisco content and activity were lowered by 10% and 60%, respectively. Antioxidant activity was stimulated by Cd treatment and was associated with an increase in the glutathione and pyridine pools, and with a larger pool of reduced glutathione. It is suggested that the glutathione pool and its predominance in the reduced state protected the activity of many key photosynthetic enzymes against the thiophilic binding of Cd. Chloroplast ultrastructure was not significantly altered with 50 micromolar treatment and the efficiency of photosystem II, measured as the fluorescence ratio F(v)/F(m), remained high because F(0) and F(m) were proportionally decreased. In plants treated with 100 micromolar Cd, all effects were exacerbated, but F(v)/F(m) remained close to that of control leaves and the glutathione and pyridine nucleotides pools were lowered. The results suggest that glutathione exerted a direct important protective role on photosynthesis in the presence of Cd.
Dynamic aeroelastic behavior of a joined-wing PrandtlPlane configuration is investigated herein. The baseline model is obtained from a configuration previously designed by partner universities ...through several multidisciplinary optimizations and ad hoc analyses, including detailed studies on the layout of control architecture. An equivalent structural model has then been adopted to qualitatively retain similar aeroelastic properties.
Flutter and post-flutter regimes, including limit cycle oscillations (LCOs), are studied. A detailed analysis of the energy transfer between fluid and structure is carried out; the areas in which energy is extracted from the fluid are identified to gain insights on the mechanism leading to the aeroelastic instability. Starting from an existing design of control surfaces on the baseline configuration, freeplay is also considered and its effects on the aeroelastic stability properties of the joined-wing system are investigated for the first time.
Both cantilever and free flying configurations are analyzed. Fuselage inertial effects are modeled and the aeroelastic properties are studied considering plunging and pitching rigid body modes. For this configuration a positive interaction between elastic and rigid body modes yields a flutter-free design (within the range of considered airspeeds).
To understand the sensitivity of the system and gain insight, fuselage mass and moment of inertia are selectively varied. For a fixed pitching moment of inertia, larger fuselage mass favors body freedom flutter. When the moment of inertia is varied, a change of critical properties is observed. For smaller values the pitching mode becomes unstable, and coalescence is observed between pitching and the first elastic mode. Increasing pitching inertia, the above criticality is postponed; meanwhile, the second elastic mode becomes unstable at progressively lower speeds. For larger inertial values “cantilever” flutter properties, having coalescence of first and second elastic modes, are recovered.
Aliment Pharmacol Ther 2010; 32: 1315–1322
Summary
Background Non‐invasive approaches are useful to differentiate simple steatosis from non‐alcoholic steatohepatitis (NASH) in obese and morbidly ...obese patients.
Aim To develop a new scoring system to diagnose definitive NASH.
Methods Preoperative clinical and biological data including serum caspase 3‐generated cytokeratin‐18 fragments (CK18) and surgical liver biopsies were obtained from 464 morbidly obese patients who had undergone bariatric surgery. The cohort was divided into two groups: training group (n = 310) and validation group (n = 154). Definitive NASH was defined according to Kleiner’s classification with a Non‐alcoholic fatty liver disease Activity Score (NAS) ≥5.
Results Alanine aminotransferase (ALT), CK18 fragments and the presence of metabolic syndrome were independent predictors for discriminating patients with NAS ≥5 in the training group. These three parameters were used to carry out a scoring system for the prediction of NAS ≥5. Whereas serum CK18 fragment alone had an area under the receiver operating characteristic (AUROC) curve = 0.74, AUROC curves of the scoring system were 0.88 and 0.83 in the training group and the validation group, respectively.
Conclusion A simple and non‐invasive composite model (the Nice Model) including metabolic syndrome, ALT and CK18 fragments is able to predict accurately a non‐alcoholic fatty liver disease activity score ≥5 in morbidly obese subjects.
Summary
Background
The composite histological endpoint comprising nonalcoholic steatohepatitis (NASH) and NAFLD activity score ≥4 and advanced fibrosis (F ≥ 2) (“fibrotic NASH”) is becoming an ...important diagnostic target in NAFLD: it is currently used to select patients for inclusion in phase III therapeutic trials and will ultimately be used to indicate treatment in clinical practice once the new drugs are approved.
Aim
To develop a new blood test specifically dedicated for this new diagnostic target of interest.
Methods
Eight Hundred and forty‐six biopsy‐proven NAFLD patients from three centres (Angers, Nice, Antwerp) were randomised into derivation and validation sets.
Results
The blood fibrosis tests BARD, NFS and FIB4 had poor accuracy for fibrotic NASH with respective AUROC: 0.566 ± 0.023, 0.654 ± 0.023, 0.732 ± 0.021. In the derivation set, fibrotic NASH was independently predicted by AST, HOMA and CK18; all three were combined in the new blood test MACK‐3 (hoMa, Ast, CK18) for which 90% sensitivity and 95% specificity cut‐offs were calculated. In the validation set, MACK‐3 had a significantly higher AUROC (0.847 ± 0.030, P ≤ 0.002) than blood fibrosis tests. Using liver biopsy in the grey zone between the two cut‐offs (36.0% of the patients), MACK‐3 provided excellent accuracy for the diagnosis of fibrotic NASH with 93.3% well‐classified patients, sensitivity: 90.0%, specificity: 94.2%, positive predictive value: 81.8% and negative predictive value: 97.0%.
Conclusion
The new blood test MACK‐3 accurately diagnoses fibrotic NASH. This new test will facilitate patient screening and inclusion in NAFLD therapeutic trials and will enable the identification of patients who will benefit from the treatments once approved.
Summary The mini-gastric bypass (MGBP) is becoming an increasingly popular procedure worldwide. It is based on an “omega” reconstruction, resulting in a single anastomosis and in potential shortening ...of operative time. Internal hernia represents a potentially life-threatening complication after laparoscopic Roux-en-Y gastric bypass, but it has not yet been reported after a mini-gastric bypass. We herein describe, for the first time, a case of internal hernia after this surgery.
Background. Bariatric surgery is an important field of surgery. An important complication of bariatric surgery is dumping syndrome (DS). Aims. To evaluate the incidence of DS in patients undergoing ...bariatric surgery. Methods. 541 patients included from 5 nutrition and bariatric centers in France underwent either LSG or LRYGB. They were evaluated at 1 month (M1) and 6 months (M6) postoperatively by an interview and completion of a dumping syndrome questionnaire. Results. 268 patients underwent LSG (Group A) and 273 underwent LRYGB. From the LRYGB patients 229 had mechanical gastrojejunoanal anastomosis with 30 mm linear stapler (Group B) and 44 had manual (hand sewn) 15 mm gastrojejunal anastomosis (Group C). Overall incidence of DS was 8.5% at M1 and M6. In LSG group (Group A), only 4 patients (1.49%) reported episodes of DS at M1 and 3 (1.12%) at M6. In Group B, 41 patients (17.90%) reported episodes of DS at M1 and 43 (18.78%) at M6. Group C experienced one case (2.27%) of DS at M1 and none (0%) at M6. Conclusions. Patients undergoing LRYGB, especially with larger gastrojejunal anastomosis, are more prone to developing DS following surgery than patients undergoing LSG or LRYGB with calibrated manual anastomosis.
At suboptimal temperatures, anthocyanins accumulate in the illuminated leaf surface of some maize genotypes and, if the anthocyanins shade chloroplasts, they can effectively reduce ...the risk of photo‐inhibition but also photo‐synthesis. To investigate this phenomenon, gas exchange, fluorescence, superoxide dismutase activity and xantho‐phyll composition of anthocyanin‐containing HOPI and anthocyanin‐deficient W22 maize genotypes were measured in either white or red light, where the latter is not absorbed by anthocyanins. Despite differences in light absorption in chloroplasts, photosynthesis did not differ between HOPI and W22 under either light source, suggesting that neither CO2 supply nor photochemistry were more limiting in red leaves than in green leaves. In fact, no major differences in transpiration were detected. The ΔF/Fm (photosystem II quantum yield) of HOPI in white light was higher than in red light and higher than ΔF/Fm of W22 with either light source. This probably compensated for the lower white light absorption of HOPI chloroplasts compared with W22 because of the presence of anthocyanins and led to similar rates of calculated electron transport for both genotypes. After exposure to high white light at 5 °C, xanthophyll de‐epoxidation and superoxide dismutase activity were lower in HOPI than in W22. Further, HOPI could be exposed to a much higher irradiance than W22 before Fv/Fm was reduced to that of W22.
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