Statins, antidiabetic medications and liver histology in patients with diabetes with non-alcoholic fatty liver disease

Background: Type-2 diabetes mellitus (T2DM) is a risk factor for progressive non-alcoholic fatty liver disease (NAFLD). Drugs commonly prescribed in patients with T2DM may affect liver histology by interfering with lipid metabolism and insulin resistance/secretion. Aim: We studied if statins or antidiabetic agents were associated with non-alcoholic steatohepatitis (NASH) and significant fibrosis (SF). Methods: We performed a cross-sectional study of 346 diabetics with biopsy-proven NAFLD. T2DM was defined as fasting glucose ≥7 mmol/L or glycated haemoglobin ≥6.5% and/or use of antidiabetics. NASH was defined according to the FLIP algorithm and SF as F2-4 Kleiner's stages. Results: 84% of patients were on antidiabetic therapy and 45% on statins. NASH and SF were present in 57% and 48% of patients. Statin-treated patients were older, more frequently male and with poorer glycaemic control despite more frequent antidiabetic therapy than those without statins; however, the prevalence of NASH (57%vs56%, p=0.868) and SF (48%vs48%, p=0.943) was not different between statin users and non-users. NASH was more common in patients on metformin or insulin than in those not treated with these drugs (60% vs47%, p=0.026; 68%vs53%, p=0.017). SF was more common in those treated with sulfonylureas (57% vs44%, p=0.030). Multivariate analyses confirmed that use of statins was independently and negatively associated with both NASH (OR (95% CI) 0.57 (0.32 to 1.01), p=0.055) and SF (OR (95% CI) 0.47 (0.26 to 0.84), p=0.011). Moreover, we found independent associations between insulin use and NASH (OR (95% CI) 2.24 (1.11 to 4.54), p=0.025) and sulfonylureas use and SF (OR (95% CI) 2.04 (1.11 to 3.74), p=0.022). Conclusions: Several medications used in patients with diabetes are differently associated with NAFLD histology. Statin use is negatively associated, while insulin and sulfonylureas are positively associated with NASH and SF. A wider use of statins may be warranted in this high-risk population

Interpretable Neural-Symbolic Concept Reasoning

Deep learning methods are highly accurate, yet their opaque decision process prevents them from earning full human trust. Concept-based models aim to address this issue by learning tasks based on a set of human-understandable concepts. However, state-of-the-art concept-based models rely on high-dimensional concept embedding representations which lack a clear semantic meaning, thus questioning the interpretability of their decision process. To overcome this limitation, we propose the Deep Concept Reasoner (DCR), the first interpretable concept-based model that builds upon concept embeddings. In DCR, neural networks do not make task predictions directly, but they build syntactic rule structures using concept embeddings. DCR then executes these rules on meaningful concept truth degrees to provide a final interpretable and semantically-consistent prediction in a differentiable manner. Our experiments show that DCR: (i) improves up to +25% w.r.t. state-of-the-art interpretable concept-based models on challenging benchmarks (ii) discovers meaningful logic rules matching known ground truths even in the absence of concept supervision during training, and (iii), facilitates the generation of counterfactual examples providing the learnt rules as guidance

Recent evolution of 129-I levels in the Nordic Seas and the North Atlantic Ocean

Most of the anthropogenic radionuclide 129I released to the marine environment from the nuclear fuel reprocessing plants (NFRP) at Sellafield (England) and La Hague (France) is transported to the Arctic Ocean via the North Atlantic Current and the Norwegian Coastal Current. 129I concentrations in seawater provides a powerful and well-established radiotracer technique to provide information about the mechanisms which govern water mass transport in the Nordic Seas and the Arctic Ocean and is gaining importance when coupled with other tracers (e.g. CFC, 236U). In this work, 129I concentrations in surface and depth profiles from the Nordic Seas and the North Atlantic (NA) Ocean collected from four different cruises between 2011 and 2012 are presented. This work allowed us to i) update information on 129I concentrations in these areas, required for the accurate use of 129I as a tracer of water masses; and ii) investigate the formation of deep water currents in the eastern part of the Nordic Seas, by the analysis of 129I concentrations and temperature-salinity (T-S) diagrams from locations within the Greenland Sea Gyre. In the Nordic Seas, 129I concentrations in seawater are of the order of 109 at·kg− 1, one or two orders of magnitude higher than those measured at the NA Ocean, not so importantly affected by the releases from the NFRP. 129I concentrations of the order of 108 atoms·kg− 1 at the Ellet Line and the PAP suggest a direct contribution from the NFRP in the NA Ocean. An increase in the concentrations in the Nordic Seas between 2002 and 2012 has been detected, which agrees with the temporal evolution of the 129I liquid discharges from the NFRPs in years prior to this. Finally, 129I profile concentrations, 129I inventories and T-S diagrams suggest that deep water formation occurred in the easternmost area of the Nordic Seas during 2012.Ministerio de Economía y Competitividad FIS2015-69673-

Effects of a Single Opioid Dose on Gastrointestinal Motility in Rabbits (Oryctolagus cuniculus): Comparisons among Morphine, Butorphanol, and Tramadol

The aim of this study was to evaluate and compare the effects of single doses of butorphanol, morphine, and tramadol on gastrointestinal motility in rabbits (Oryctolagus cuniculus) using non-invasive imaging methods, such as radiographic barium follow through and ultrasonographic contraction counts. Time-lapse radiographic and ultrasound examinations were performed before and after a single intramuscular dose of 5 mg kg−1 butorphanol, 10 mg kg−1 morphine, or 10 mg kg−1 tramadol. Pyloric and duodenal contraction counts by ultrasonography and radiographic repletion scores for the stomach and caecum were analysed using a mixed linear model. No significant effect was noted on ultrasound examinations of pyloric and duodenal contractions after administration of an opioid treatment. Morphine had a significant effect on the stomach and the caecum repletion scores, whereas butorphanol had a significant effect only on the caecum repletion score. Tramadol had no significant effect on the stomach or caecum repletion scores. The present findings suggest that a single dose of 5 mg kg−1 butorphanol or 10 mg kg−1 morphine temporarily slows gastrointestinal transit in healthy rabbits, preventing physiological progression of the alimentary bolus without the induction of ileus. In contrast, a single dose of 10 mg kg−1 tramadol has no such effect

Methicillin-Resistant Staphylococcus capitis with Reduced Vancomycin Susceptibility Causes Late-Onset Sepsis in Intensive Care Neonates

isolated from the blood of NICU infants and compared these data to adult patients. element, and constantly showed either vancomycin resistance (37.5%) or heteroresistance (62.5%). Conversely, the isolates that were collected outside of the NICU were genetically diverse and displayed much lower rates of vancomycin resistance and heteroresistance (7.7% and 23.1%, respectively). strains has spread into several French NICUs. These isolates exhibit reduced susceptibility to vancomycin, which is the most widely used antimicrobial agent in the NICU setting

Characterization of social behavior in young and middle-aged ChAT-IRES-Cre mouse

The cholinergic system is an important modulator of brain processes. It contributes to the regulation of several cognitive functions and emotional states, hence altering behaviors. Previous works showed that cholinergic (nicotinic) receptors of the prefrontal cortex are needed for adapted social behaviors. However, these data were obtained in mutant mice that also present alterations of several neurotransmitter systems, in addition to the cholinergic system. ChAT-IRES-Cre mice, that express the Cre recombinase specifically in cholinergic neurons, are useful tools to investigate the role of the cholinergic circuits in behavior. However, their own behavioral phenotype has not yet been fully characterized, in particular social behavior. In addition, the consequences of aging on the cholinergic system of ChAT-IRES-Cre mice has never been studied, despite the fact that aging is known to compromise the cholinergic system efficiency. The aim of the current study was thus to characterize the social phenotype of ChAT-IRES-Cre mice both at young (2–3 months) and middle (10–11 months) ages. Our results reveal an alteration of the cholinergic system, evidenced by a decrease of ChAT, CHT and VAChT gene expression in the striatum of the mice, that was accompanied by mild social disturbances and a tendency towards anxiety. Aging decreased social dominance, without being amplified by the cholinergic alterations. Altogether, this study shows that ChAT-IRES-Cre mice are useful models for studying the cholinergic system‘s role in social behavior using appropriate modulating technics (optogenetic or DREADD). </p

Three cases of severe subfulminant hepatitis in heart-transplanted patients after nosocomial transmission of a mutant hepatitis B virus

Fulminant and severe viral hepatitis are frequently associated with mutant hepatitis B virus (HBV) strains. In this study, the genetic background of a viral strain causing severe subfulminant outcome in heart-transplanted patients was studied and compared with viral hepatitis B strains that were not linked to severe liver disease in the same setting. A total of 46 patients infected nosocomially with HBV genotype A were studied. Five different viral strains were detected, infecting 3, 9, 5, 24, and 5 patients, respectively. Only one viral strain was found to be associated with the subfulminant outcome and 3 patient deaths as a consequence of severe liver disease. The remaining 43 patients with posttransplantation HBV infection did not show this fatal outcome. Instead, symptoms of hepatitis were generally mild or clinically undiagnosed. Comparison of this virus genome with the four other strains showed an accumulation of mutations in the basic core promoter, a region that influences viral replication, but also in hepatitis B X protein (HBX) (7 mutant motifs), core (10 mutant motifs), the preS1 region (5 mutant motifs), and the HBpolymerase open reading frame (17 motifs). Some of these variations, such as those in the core region, were located on the tip of the protruding spike of the viral capsid (codons 60 to 90), also known in part as an important HLA class II-restricted epitope region. These mutations might therefore influence the immune-mediated response. The viral strain causing subfulminant hepatitis was, in addition, the only strain with a preCore stop codon mutation and, thus, hepatitis B e antigen (HBeAg) expression was never observed. The combination of these specific viral factors is thought to be responsible for the fatal outcome in these immune-suppressed heart-transplant recipients

The diagnostic value of biomarkers (SteatoTest) for the prediction of liver steatosis

BACKGROUND: Biopsy is the usual gold standard for liver steatosis assessment. The aim of this study was to identify a panel of biomarkers (SteatoTest), with sufficient predictive values, for the non-invasive diagnosis of steatosis in patients with or without chronic liver disease. Biomarkers and panels were assessed in a training group of consecutive patients with chronic hepatitis C and B, alcoholic liver disease, and non-alcoholic fatty liver disease, and were validated in two independent groups including a prospective one. Steatosis was blindly assessed by using a previously validated scoring system. RESULTS: 310 patients were included in the training group; 434 in three validation groups; and 140 in a control group. SteatoTest was constructed using a combination of the 6 components of FibroTest-ActiTest plus body mass index, serum cholesterol, triglycerides, and glucose adjusted for age and gender. SteatoTest area under the ROC curves was 0.79 (SE = 0.03) in the training group; 0.80 (0.04) in validation group 1; 0.86 (0.03) in validation group 2; and 0.72 (0.05) in the validation group 3 – all significantly higher than the standard markers: γ-glutamyl-transpeptidase or alanine aminotransferase. The median SteatoTest value was 0.13 in fasting controls; 0.16 in non-fasting controls; 0.31 in patients without steatosis; 0.39 in grade 1 steatosis (0–5%); 0.58 in grade 2 (6–32%); and 0.74 in grade 3–4 (33–100%). For the diagnosis of grade 2–4 steatosis, the sensitivity of SteatoTest at the 0.30 cut-off was 0.91, 0.98, 1.00 and 0.85 and the specificity at the 0.70 cut-off was 0.89, 0.83, 0.92, 1.00, for the training and three validation groups, respectively. CONCLUSION: SteatoTest is a simple and non-invasive quantitative estimate of liver steatosis and may reduce the need for liver biopsy, particularly in patients with metabolic risk factor