Are the Expanded Baveno VI Criteria really safe to screen compensated cirrhotic patients for high-risk varices?

The Expanded Baveno VI criteria [1] have been recently proposed as a new screening strategy for high-risk varices (HRV), able to increase the rate of spared upper endoscopies (EGDs) and improve upon the original Baveno VI Criteria [2]. To date, few studies have investigated the performance and safety of these criteria [3,4]. The recent work by Bae et al. [4] is the first one to report a high rate (>5%) of missed HRV by the expanded criteria, questioning their efficiency in safely ruling out HRV (sensitivity 81%, NPV 93%, LR- 0.30

The angular momentum of disc galaxies at z=1

We investigate the relation between stellar mass and specific stellar angular momentum, or `Fall relation', for a sample of 17 isolated, regularly rotating disc galaxies at z=1. All galaxies have a) rotation curves determined from Halpha emission-line data; b) HST imaging in optical and infrared filters; c) robust determinations of their stellar masses. We use HST images in f814w and f160w filters, roughly corresponding to rest-frames B and I bands, to extract surface brightness profiles for our systems. We robustly bracket the specific angular momentum by assuming that rotation curves beyond the outermost Halpha rotation point stay either flat or follow a Keplerian fall-off. By comparing our measurements with those determined for disc galaxies in the local Universe, we find no evolution in the Fall relation in the redshift range 0<z<1, regardless of the band used and despite the uncertainties in the stellar rotation curves at large radii. This result holds unless stellar masses at z=1 are systematically underestimated by more than 50%. Our findings are compatible with expectations based on a LCDM cosmological framework and support a scenario where both the stellar Tully-Fisher and mass-size relations for spirals do not evolve significantly in this redshift range.Comment: 11 pages, 4 figures, 1 table. Accepted by A&

Successful application of PSF-R techniques to the case of the globular cluster NGC 6121 (M 4)

Context. Precise photometric and astrometric measurements on astronomical images require an accurate knowledge of the point spread function (PSF). When the PSF cannot be modelled directly from the image, PSF-reconstruction techniques become the only viable solution. So far, however, their performance on real observations has rarely been quantified. Aims. In this Letter, we test the performance of a novel hybrid technique, called PRIME, on Adaptive Optics-assisted SPHERE/ZIMPOL observations of the Galactic globular cluster NGC 6121. Methods. PRIME couples PSF-reconstruction techniques, based on control-loop data and direct image fitting performed on the only bright point-like source available in the field of view of the ZIMPOL exposures, with the aim of building the PSF model. Results. By exploiting this model, the magnitudes and positions of the stars in the field can be measured with an unprecedented precision, which surpasses that obtained by more standard methods by at least a factor of four for on-axis stars and by up to a factor of two on fainter, off-axis stars. Conclusions. Our results demonstrate the power of PRIME in recovering precise magnitudes and positions when the information directly coming from astronomical images is limited to only a few point-like sources and, thus, paving the way for a proper analysis of future Extremely Large Telescope observations of sparse stellar fields or individual extragalactic objects

Physiological tissue-specific and age-related reduction of mouse TDP-43 levels is regulated by epigenetic modifications

The cellular level of TDP-43 (also known as TARDBP) is tightly regulated; increases or decreases in TDP-43 have deleterious effects in cells. The predominant mechanism responsible for the regulation of the level of TDP-43 is an autoregulatory negative feedback loop. In this study, we identified an in vivo cause-effect relationship between Tardbp gene promoter methylation and specific histone modification and the TDP-43 level in tissues of mice at two different ages. Furthermore, epigenetic control was observed in mouse and human cultured cell lines. In amyotrophic lateral sclerosis, the formation of TDP-43-containing brain inclusions removes functional protein from the system. This phenomenon is continuous but compensated by newly synthesized protein. The balance between sequestration and new synthesis might become critical with ageing, if accompanied by an epigenetic modification-regulated decrease in newly synthesized TDP-43. Sequestration by aggregates would then decrease the amount of functional TDP-43 to a level lower than those needed by the cell and thereby trigger the onset of symptoms

Somatostatin: A Novel Substrate and a Modulator of Insulin-Degrading Enzyme Activity

Insulin-degrading enzyme (IDE) is an interesting pharmacological target for Alzheimer's disease (AD), since it hydrolyzes beta-amyloid, producing non-neurotoxic fragments. It has also been shown that the somatostatin level reduction is a pathological feature of AD and that it regulates the neprilysin activity toward beta-amyloid. In this work, we report for the first time that IDE is able to hydrolyze somatostatin [k(cat) (s(-1)) = 0.38 (+/-0.05); K-m (M) = 7.5 (+/-0.9) x 10(-6)] at the Phe6-Phe7 amino acid bond. On the other hand, somatostatin modulates IDE activity, enhancing the enzymatic cleavage of a novel fluorogenic beta-amyloid through a decrease of the K-m toward this substrate, which corresponds to the 10-25 amino acid sequence of the A beta(1-40). Circular dichroism spectroscopy and surface plasmon resonance imaging experiments show that somatostatin binding to IDE brings about a concentration-dependent structural change of the secondary and tertiary structure(s) of the enzyme, revealing two possible binding sites. The higher affinity binding site disappears upon inactivation of IDE by ethylenediaminetetra acetic acid, which chelates, the catalytic Zn2+ ion. As a whole, these features suggest that the modulatory effect is due to an allosteric mechanism: somatostatin binding to the active site of one IDE subunit (where somatostatin is cleaved) induces an enhancement of IDE proteolytic activity toward fluorogenic beta-amyloid by another subunit. Therefore, this investigation on IDE-somatostatin interaction contributes to a more exhaustive knowledge about the functional and structural aspects of IDE and its pathophysiological implications in the amyloid deposition and somatostatin homeostasis in the brain. (C) 2008 Elsevier Ltd. All rights reserved

Femoral Artery Atherosclerosis Is Associated With Physical Function Across the Spectrum of the Ankle-Brachial Index: The San Diego Population Study.

BackgroundThe ankle-brachial index (ABI) is inadequate to detect early-stage atherosclerotic disease, when interventions to prevent functional decline may be the most effective. We determined associations of femoral artery atherosclerosis with physical functioning, across the spectrum of the ABI, and within the normal ABI range.Methods and resultsIn 2007-2011, 1103 multiethnic men and women participated in the San Diego Population Study, and completed all components of the summary performance score. Using Doppler ultrasound, superficial and common femoral intima media thickness and plaques were ascertained. Logistic regression was used to assess associations of femoral atherosclerosis with the summary performance score and its individual components. Models were adjusted for demographics, lifestyle factors, comorbidities, lipids, and kidney function. In adjusted models, among participants with a normal-range ABI (1.00-1.30), the highest tertile of superficial intima media thickness was associated with lower odds of a perfect summary performance score of 12 (odds ratio=0.56 [0.36, 0.87], P=0.009), and lower odds of a 4-m walk score of 4 (0.34 [0.16, 0.73], P=0.006) and chair rise score of 4 (0.56 [0.34, 0.94], P=0.03). Plaque presence (0.53 [0.29, 0.99], P=0.04) and greater total plaque burden (0.61 [0.43, 0.87], P=0.006) were associated with worse 4-m walk performance in the normal-range ABI group. Higher superficial intima media thickness was associated with lower summary performance score in all individuals (P=0.02).ConclusionsFindings suggest that use of femoral artery atherosclerosis measures may be effective in individuals with a normal-range ABI, especially, for example, those with diabetes mellitus or a family history of peripheral artery disease, when detection can lead to earlier intervention to prevent functional declines and improve quality of life

Antibiotic prophylaxis in patients with cirrhosis: Current evidence for clinical practice

Patients with cirrhosis show an increased susceptibility to infection due to disease-related immune-dysfunction. Bacterial infection therefore represents a common, often detrimental event in patients with advanced liver disease, since it can worsen portal hypertension and impair the function of hepatic and extrahepatic organs. Among pharmacological strategies to prevent infection, antibiotic prophylaxis remains the first-choice, especially in high-risk groups, such as patients with acute variceal bleeding, low ascitic fluid proteins, and prior episodes of spontaneous bacterial peritonitis. Nevertheless, antibiotic prophylaxis has to deal with the changing bacterial epidemiology in cirrhosis, with increased rates of gram-positive bacteria and multidrug resistant rods, warnings about quinolones-related side effects, and low prescription adherence. Short-term antibiotic prophylaxis is applied in many other settings during hospitalization, such as before interventional or surgical procedures, but often without knowledge of local bacterial epidemiology and without strict adherence to antimicrobial stewardship. This paper offers a detailed overview on the application of antibiotic prophylaxis in cirrhosis, according to the current evidence

A brief introduction to nomography: graphical representation of mathematical relationships

© 2018, © 2018 Informa UK Limited, trading as Taylor & Francis Group. Nomographs (or nomograms, or alignment charts) are graphical representations of mathematical relationships (extending to empirical relationships of data) which are used by simply applying a straightedge across the plot through points on scales representing independent variables, which then crosses the corresponding datum point for the dependent variable; the choice among independent and dependent variable is arbitrary so that each variable may be determined in terms of the others. Examples of nomographs in common current use compute the lift available for a hot-air balloon, the boiling points of solvents under reduced pressure in the chemistry laboratory, and the relative forces in a centrifuge in a biochemical laboratory. Sundials represent another ancient yet widely familiar example. With the advent and ready accessibility of the computer, printed mathematical tables, slide rules and nomographs became generally redundant. However, nomographs provide insight into mathematical relationships, are useful for rapid and repeated application, even in the absence of calculational facilities, and can reliably be used in the field. Many nomographs for various purposes may be found online. This paper describes the origins and development of nomographs, illustrating their use with some relevant examples. A supplementary interactive Excel file demonstrates their application for some simple mathematical operations

Geraniol Treatment for Irritable Bowel Syndrome: A Double-Blind Randomized Clinical Trial

Geraniol is an acyclic monoterpene alcohol with well-known anti-inflammatory and antimicrobial properties which has shown eubiotic activity towards gut microbiota (GM) in patients with irritable bowel syndrome (IBS). Methods: Fifty-six IBS patients diagnosed according to Rome III criteria were enrolled in an interventional, prospective, multicentric, randomized, double-blinded, placebo-controlled trial. In the treatment arm, patients received a low-absorbable geraniol food supplement (LAGS) once daily for four weeks. Results: Patients treated with LAGS showed a significant reduction in their IBS symptoms severity score (IBS-SSS) compared to the placebo (195 vs. 265, p = 0.001). The rate of responders according to IBS-SSS (reduction ≥ 50 points) was significantly higher in the geraniol vs placebo group (52.0% vs. 16.7%, p = 0.009) mainly due to the IBS mixed subtype. There were notable differences in the microbiota composition after geraniol administration, particularly a significant decrease in a genus of Ruminococcaceae, Oscillospira (p = 0.01), a decreasing trend for the Erysipelotrichaceae and Clostridiaceae families (p = 0.1), and an increasing trend for other Ruminococcaceae taxa, specifically Faecalibacterium (p = 0.09). The main circulating proinflammatory cytokines showed no differences between placebo and geraniol arms. Conclusion: LAGS was effective in treating overall IBS symptoms, together with an improvement in the gut microbiota profile, especially for the IBS mixed subtype