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The present work reports the thermal performance of a box-type solar cooker insulated with kapok wool, a local plant with a low thermal conductivity. The experimental results obtained indicate that the absorber plate reached a maximum temperature of 155.2 °C. Moreover, the maximum power of the cooker was 87.5 W with an efficiency of 35.45 %. The first and second figure of merit parameters performed are 0.15 and 0.298 respectively. The cooking test carried out on eggs and rice was conclusive. And it appears that this solar cooker can cook an average of 464 meals per year thanks to the solar energy available in Burkina Faso corresponding to a reduction of 67.62 % in household fuel wood consumption.

The antiplasmodium assay-guided investigation of the roots, stem bark, and leaves of Persea americana Mill. led to the isolation of a new fatty alcohol, perseatriol (1), along with six known compounds (2–7). Their structures were elucidated based on the analysis of their NMR and MS data. All crude extracts and fractions exhibited good antiplasmodial activity on Plasmoduim falciparum 3D7 with IC50 values ranging from 0.76 to 10.5 μg/mL; they also displayed cytotoxicity against HeLa cells with low selectivity indexes (SIs). A preliminary Plasmodium lactate dehydrogenase (pLDH) assay was also performed on the isolated compounds. 9,9′-Di-O-feruloyl-5,5′-dimethoxysecoisolariciresinol (4) turned out to be non-toxic and displayed the best activities on P. falciparum with an IC50 value of 0.05 μM, comparable to the reference drug chloroquine with an IC50 value of 0.03 μM. Furthermore, besides compound 4, this work reports the first isolation of lutein (2) and scopoletin (3) from P. americana. The crude extracts of roots, stem bark, and leaves of P. americana, their fractions and compounds completely suppressed the growth of P. falciparum. The observed activity supports the use of P. americana in folk medicine for the treatment of malaria.

Background & Aims Non-alcoholic fatty liver disease (NAFLD) has become a major public health problem, but the prevalence of fibrosis associated with non-alcoholic steatohepatitis (NASH) is largely unknown in the general population. This study aimed to provide an updated estimation of the prevalence of NASH fibrosis in Spain. Methods This was an observational, retrospective, cross-sectional, population-based study with merged data from two Spanish datasets: a large (N = 12 246) population-based cohort (ETHON), including transient elastography (TE) data, and a contemporary multi-centric biopsy-proven NASH cohort with paired TE data from tertiary centres (N = 501). Prevalence for each NASH fibrosis stage was estimated by crossing TE data from ETHON dataset with histology data from the biopsy-proven cohort. Results From the patients with valid TE in ETHON dataset (N = 11 440), 5.61% (95% confidence interval [95% CI]: 2.53-11.97) had a liver stiffness measurement (LSM) >= 8 kPa. The proportion attributable to NAFLD (using clinical variables and Controlled Attenuation Parameter) was 57.3% and thus, the estimated prevalence of population with LSM >= 8 kPa because of NAFLD was 3.21% (95% CI 1.13-8.75). In the biopsy-proven NASH cohort, 389 patients had LSM >= 8 kPa. Among these, 37% did not have significant fibrosis (F2-4). The estimated prevalence of NASH F2-3 and cirrhosis in Spain's adult population were 1.33% (95% CI 0.29-5.98) and 0.70% (95% CI 0.10-4.95) respectively. Conclusions These estimations provide an accurate picture of the current prevalence of NASH-related fibrosis in Spain and can serve as reference point for dimensioning the therapeutic efforts that will be required as NASH therapies become available.

Phytochemical investigation of dichloromethane neutral phase of stem bark of Nauclea pobeguinii led to the isolation of a new monoterpene indole alkaloid, pobeguinine 1 along with 14 known compounds including (−)-naucleofficine D (2a), (+)-naucleofficine D (2b), naucleidinal (3), quafrinoic acid (4), betulinic acid (5), ursolic acid (6), quinovic acid (7), quinovic acid 3-O-α-L-rhamnopyranoside (8a), quinovic acid 3-O-β-D-fucopyranoside (8b), β-sitosterol (9), β-sitosterol 3-O-β-D-glucopyranoside (10), benzoic acid (11), lacceroic acid (12) and n-heptacosane (13). The structure of compound 1 was unambiguously assigned on the basis of single-crystal X-ray diffraction technique. The Hirshfeld surface analysis was further carried out to quantitatively analyze the role of various types of hydrogen bonding in crystal stability. These structures were elucidated using spectroscopic methods. The isolates were evaluated for their radical scavenging properties as well as inhibitory activities against urease and tyrosinase enzymes with IC50 values ranging from 13.4 to 58.9, 46.0 to 86.7 and 39.4 to 87.1 μg/mL, respectively. Compound 6 exhibited maximum radical scavenging activity with IC50 13.4 μg/mL, while compound 4 exhibited maximum tyrosinase with IC50 39.4 μg/mL. All the isolates showed moderate urease inhibition.

Background: Clinical decompensation of cirrhosis is associated with poor prognosis. Clinically significant portal hypertension (CSPH), defined by a hepatic venous pressure gradient (HVPG) =10 mm Hg, is the strongest predictor of decompensation. This study aimed at assessing whether lowering HVPG with ß blockers could decrease the risk of decompensation or death in compensated cirrhosis with CSPH. Methods: This study on ß blockers to prevent decompensation of cirrhosis with portal hypertension (PREDESCI) was an investigator-initiated, double-blind, randomised controlled trial done in eight hospitals in Spain. We enrolled patients with compensated cirrhosis and CSPH without high-risk varices. All participants had HVPG measurements with assessment of acute HVPG-response to intravenous propranolol. Responders (HVPG-decrease =10%) were randomly assigned to propranolol (up to 160 mg twice a day) versus placebo and non-responders to carvedilol (=25 mg/day) versus placebo. Doses were individually determined during an open-label titration period after which randomisation was done with 1:1 allocation by a centralised web-based system. The primary endpoint was incidence of cirrhosis decompensation (defined as development of ascites, bleeding, or overt encephalopathy) or death. Since death in compensated cirrhosis is usually unrelated to the liver, an intention-to-treat analysis considering deaths unrelated to the liver as competing events was done. This study is registered with ClinicalTrials.gov, number NCT01059396. The trial is now completed. Findings: Between Jan 18, 2010, and July 31, 2013, 631 patients were evaluated and 201 were randomly assigned. 101 patients received placebo and 100 received active treatment (67 propranolol and 33 carvedilol). The primary endpoint occurred in 16 (16%) of 100 patients in the ß blockers group versus 27 (27%) of 101 in the placebo group (hazard ratio [HR] 0·51, 95% CI 0·26–0·97, p=0·041). The difference was due to a reduced incidence of ascites (HR=0·44, 95%CI=0·20–0·97, p=0·0297). The overall incidence of adverse events was similar in both groups. Six patients (four in the ß blockers group) had severe adverse events. Interpretation: Long-term treatment with ß blockers could increase decompensation-free survival in patients with compensated cirrhosis and CSPH, mainly by reducing the incidence of ascites. Funding: Spanish Ministries of Health and Economy. © 2019 Elsevier Ltd

Patients admitted with acute variceal bleeding (AVB) and Child-Pugh C score (CP-C) or Child-Pugh B plus active bleeding at endoscopy (CP-B+AB) are at high risk for treatment failure, rebleeding, and mortality. A preemptive transjugular intrahepatic portosystemic shunt (p-TIPS) has been shown to improve survival in these patients, but its use in clinical practice has been challenged and not routinely incorporated. The present study aimed to further validate the role of preemptive TIPS in a large number of high-risk patients. This multicenter, international, observational study included 671 patients from 34 centers admitted for AVB and high risk of treatment failure. Patients were managed according to current guidelines, and use of drugs and endoscopic therapy (D+E) or p-TIPS was based on individual center policy. p-TIPS in the setting of AVB is associated with a lower mortality in CP-C patients compared with D+E (1 year mortality 22% vs. 47% in D+E group; P = 0.002). Mortality rate in CP-B+AB patients was low, and p-TIPS did not improve it. In CP-C and CP-B+AB patients, p-TIPS reduced treatment failure and rebleeding (1-year cumulative incidence function probability of remaining free of the composite endpoint: 92% vs. 74% in the D+E group; P = 0.017) and development of de novo or worsening of previous ascites without increasing rates of hepatic encephalopathy. Conclusion: p-TIPS must be the treatment of choice in CP-C patients with AVB. Because of the strong benefit in preventing further bleeding and ascites, p-TIPS could be a good treatment strategy for CP-B+AB patients. ispartof: HEPATOLOGY vol:69 issue:1 pages:282-293 ispartof: location:United States status: published

Patients admitted with acute variceal bleeding (AVB) and Child-Pugh C score (CP-C) or Child-Pugh B plus active bleeding at endoscopy (CP-B+AB) are at high risk for treatment failure, rebleeding, and mortality. A preemptive transjugular intrahepatic portosystemic shunt (p-TIPS) has been shown to improve survival in these patients, but its use in clinical practice has been challenged and not routinely incorporated. The present study aimed to further validate the role of preemptive TIPS in a large number of high-risk patients. This multicenter, international, observational study included 671 patients from 34 centers admitted for AVB and high risk of treatment failure. Patients were managed according to current guidelines, and use of drugs and endoscopic therapy (D+E) or p-TIPS was based on individual center policy. p-TIPS in the setting of AVB is associated with a lower mortality in CP-C patients compared with D+E (1 year mortality 22% vs. 47% in D+E group; P = 0.002). Mortality rate in CP-B+AB patients was low, and p-TIPS did not improve it. In CP-C and CP-B+AB patients, p-TIPS reduced treatment failure and rebleeding (1-year cumulative incidence function probability of remaining free of the composite endpoint: 92% vs. 74% in the D+E group; P = 0.017) and development of de novo or worsening of previous ascites without increasing rates of hepatic encephalopathy. Conclusion: p-TIPS must be the treatment of choice in CP-C patients with AVB. Because of the strong benefit in preventing further bleeding and ascites, p-TIPS could be a good treatment strategy for CP-B+AB patients.

Background Clinical decompensation of cirrhosis is associated with poor prognosis. Clinically significant portal hypertension (CSPH), defined by a hepatic venous pressure gradient (HVPG) >= 10 mm Hg, is the strongest predictor of decompensation. This study aimed at assessing whether lowering HVPG with beta blockers could decrease the risk of decompensation or death in compensated cirrhosis with CSPH. Methods This study on beta blockers to prevent decompensation of cirrhosis with portal hypertension (PREDESCI) was an investigator-initiated, double-blind, randomised controlled trial done in eight hospitals in Spain. We enrolled patients with compensated cirrhosis and CSPH without high-risk varices. All participants had HVPG measurements with assessment of acute HVPG-response to intravenous propranolol. Responders (HVPG-decrease >= 10%) were randomly assigned to propranolol (up to 160 mg twice a day) versus placebo and non-responders to carvedilol (

Les paramètres météorologiques et radiométriques tels que le rayonnement solaire influencent fondamentalement la rentabilité et la performance des systèmes de conversion de l’énergie solaire. L’optimisation des convertisseurs d’énergie solaire dépend du modèle de rayonnement solaire utilisé. Cette étude porte sur l’estimation du rayonnement solaire incident global sur le plan horizontal et incliné sur le site de la ville de Ouagadougou. L’étude des quatre modèles de rayonnement solaire permet d’estimer le rayonnement solaire global incident sur un plan horizontal et incliné. Les différents modèles sont évalués sur une base graphique et statistique, en utilisant les indicateurs du coefficient de détermination de R^2, de l’erreur quadratique moyenne (RMSE) et le pourcentage de l'erreur absolue moyenne (MAPE). Les résultats obtenus avec les quatre modèles semi-empiriques ont été comparés avec les valeurs expérimentales instantanées mesurées sur le site de Ouagadougou. Les résultats montrent que le modèle semiempirique d’Eufrat présente la meilleure estimation du rayonnement solaire global pour le site de Ouagadougou.

Two previously undescribed ceramides, named celtisamide A (1) and B (2), along with 16 known compounds (3-18), were isolated both from the stem bark and roots of Celtis tessmannii Rendle. The isolated compounds were assessed in vitro for their DPPH radical scavenging, antiplasmodial activity as well as their urease and lipoxygenase inhibitory properties. In addition, fractions and extracts were also evaluated for antiplasmodial and cytotoxicity activities against HEK293T. Cis-1-O-methylinositol (17) (IC50 = 14.3 µM) was the most potent inhibitor of urease, while succinic acid (18) (IC50 = 12.9 µM) exhibited the best inhibition against lipoxygenase. Compound 18 (IC50 = 9.5 µM) showed the best DPPH radical scavenging activity. Extracts and fractions exhibited varying degree of antiplasmodial potency with IC50 values ranging from 2.42-100.00 µg/mL, while betulinic acid (7) showed potency with IC50 values ranging from 1.87-2.34 µg/mL against Chloroquine-sensitive (Pf3D7), and Chloroquine-resistant (PfDd2 and PfINDO) strains of Plasmodium falciparum.

Urease enzyme (UE) has been reported to be a potent virulence factor for Helicobacter pylori (HP) bacteria indicated to be responsible for various gastrointestinal diseases. Therefore, the spread of HP, currently regarded by the World Health Organization as a class 1 carcinogen, could be better controlled by targeting UE. It is in this line that we have synthesized three new derivatives (2–4) of the naturally occurring olean-12-en-3-one (1), which was previously isolated from the figs of Ficus vallis-choudae Delile (Moraceae). Among the synthesized compounds, 3 and 4 contain an indole moiety. Their structures were unambiguously assigned by spectroscopic and spectrometric techniques (1D-NMR, 2D-NMR and MS). The starting material and the synthesized compounds were screened for UE inhibition activity, and showed significant activities with IC50 values ranging from 14.5 to 24.6 μM, with compound (1) being the most potent as compared to the positive control thiourea (IC50 = 21.6 μM). Amongst the synthetic derivatives, compound 4 was the most potent (IC50 = 17.9 μM), while the others showed activities close to that of the control. In addition, molecular docking study of target compounds 2–4 was performed in an attempt to explore their binding mode for the design of more potent UE inhibitors. Graphical Abstract Electronic supplementary material The online version of this article (10.1007/s13659-018-0193-7) contains supplementary material, which is available to authorized users.

Background Non-alcoholic fatty liver disease (NAFLD) is the most prevalent chronic liver disease and is found in 70% of obese people. The evidence available to date suggests that bariatric surgery could be an effective treatment by reducing weight and also by improving metabolic complications in the long term. This work aimed to compare, in a diet-induced NAFLD animal model, the effect of both sleeve gastrectomy (SG) and very-low calorie diet (VLCD). Methods Thirty-five Wistar rats were divided into control rats (n = 7) and obese rats fed a high-fat diet (HFD). After 10 weeks, the obese rats were subdivided into four groups: HFD (n = 7), VLCD (n = 7), and rats submitted to either a sham operation (n = 7) or SG (n = 7). Both liver tissue and blood samples were processed to evaluate steatosis and NASH changes in histology (Oil Red, Sirius Red and H & presence of endothelial damage (CD31, Moesin/p-Moesin, Akt/p-Akt, eNOS/p-eNOS), oxidative stress (iNOS) and fibrosis (alpha SMA, Col1, PDGF, VEGF) proteins in liver tissue; and inflammatory (IL6, IL10, MCP-1, IL17 alpha, TNF alpha), liver biochemical function, and hormonal (leptin, ghrelin, visfatin and insulin) alterations in plasma. Results Both VLCD and SG improved histology, but only SG induced a significant weight loss, improved endothelial damage, and a decreased cardiovascular risk by reducing insulin resistance (IR), leptin, total cholesterol, and triglyceride levels. There were no relevant variations in the inflammatory and fibrosis markers. Conclusion Our study suggests a slight superiority of SG over VLCD by improving not only the histology but also the IR and cardiovascular risk markers related to NAFLD.

We examine the cross-country dispersion in fiscal outcomes during 2008–09. Controlling for output, we find that the declines in the overall and structural fiscal balances were larger for those countries experiencing larger increases in unemployment and where credit growth during the pre-crisis period was more rapid. However, controlling for output and unemployment, there is no systematic covariation between fiscal outcomes and a wider range of initial conditions and country characteristics that have been cited as possible drivers of fiscal outcomes during this episode.

In this study, favorable conditions to achieve good combustion of cottonseed oil and its blends with diesel fuel in a direct injection diesel engine have been highlighted. This has been performed by analyzing fuel droplet size distribution and determining engine specific fuel consumption and thermal efficiency, combustion parameters (ignition delay, rate of heat release) and emissions (carbon monoxide (CO), nitrogen oxides (NOx) and carbon dioxide (CO2)). Results show that thermal efficiency and CO2 are almost similar for all tested fuels while the specific fuel consumption and CO emissions increase and NOx emissions decrease with increasing percentage of cottonseed oil in blends. Cylinder pressures are very close and rates of heat release are slightly different for cottonseed oil and diesel fuel. Results on droplet size analysis show that to obtain an adequate droplet size distribution, the percentage of cottonseed oil in diesel fuel should be limited to 40% by volume. Results on engine performance show that engine loads must be above 50%. These results are valid for diesel engines of conventional design, using low-pressure injection systems; they do not apply to modern high injection pressure engines.

Recent studies have shown that liver cirrhosis (LC) behaves as an acquired hypercoagulable state with increased thrombotic risk. This is why anticoagulation therapy (AT) is now frequently used in these patients. Variceal bleeding is a severe complication of LC. It is unknown whether AT may impact the outcome of bleeding in these patients. Fifty-two patients on AT with upper gastrointestinal bleeding (UGIB) were evaluated. Portal vein thrombosis (PVT) and different cardiovascular disorders (CVDs) were the indication for AT in 14 and 38 patients, respectively. Overall, 104 patients with LC and UGIB not under AT matched for severity of LC, age, sex, source of bleeding, and Sequential Organ Failure Assessment (SOFA) score served as controls. UGIB was attributed to portal hypertension (PH) in 99 (63%) patients and peptic/vascular lesions in 57 (37%). Twenty-six (17%) patients experienced 5-day failure; SOFA, source of UGIB, and PVT, but not AT, were independent predictors of 5-day failure. In addition, independent predictors of 6-week mortality, which was observed in 26 (11%) patients, were SOFA, Charlson Comorbidity index, and use of AT for a CVD. There were no differences between patients with/without AT in needs for rescue therapies, intensive care unit admission, transfusions, and hospital stay. Conclusions: Factors that impact the outcome of UGIB in patients under AT are degree of multiorgan failure and comorbidity, but not AT itself. (Hepatology 2015;62:575-583

© 2015 Cases et al., Myopia is a common ocular disorder generally due to increased axial length of the eye-globe. Its extreme form high myopia (HM) is a multifactorial disease leading to retinal and scleral damage, visual impairment or loss and is an important health issue. Mutations in the endocytic receptor LRP2 gene result in Donnai-Barrow (DBS) and Stickler syndromes, both characterized by HM. To clearly establish the link between Lrp2 and congenital HM we inactivated Lrp2 in the mouse forebrain including the neural retina and the retinal and ciliary pigment epithelia. High resolution in vivo MRI imaging and ophthalmological analyses showed that the adult Lrp2-deficient eyes were 40% longer than the control ones mainly due to an excessive elongation of the vitreal chamber. They had an apparently normal intraocular pressure and developed chorioretinal atrophy and posterior scleral staphyloma features reminiscent of human myopic retinopathy. Immunomorphological and ultrastructural analyses showed that increased eye lengthening was first observed by post-natal day 5 (P5) and that it was accompanied by a rapid decrease of the bipolar, photoreceptor and retinal ganglion cells, and eventually the optic nerve axons. It was followed by scleral thinning and collagen fiber disorganization, essentially in the posterior pole. We conclude that the function of LRP2 in the ocular tissues is necessary for normal eye growth and that the Lrp2-deficient eyes provide a unique tool to further study human HM., Funding provided by RK Institut National sur la Recherche Médicale ANR-10-LABX-65, ANR11-IDEX-004-02, and Sanofi FDC MINECO SAF 2012-40023, R012-003212.

Within this thesis, the non-linear creation of electron-positron pairs in the superposition of a nuclear Coulomb field and a two-colour laser field of high intensity is studied. Primarily, two complementary scenarios are investigated: On the one hand, if the two laser frequencies are commensurable, quantum interference may occur. This interference manifests in the total pair-creation rate and the angular distribution of the created particles, which are studied in the nuclear rest frame and the laboratory frame. Furthermore, the relative phase between the two laser modes allows to tune the strength of the terms arising from interference. Therefore, this parameter may be used to optimize the pair-creation yield. On the other hand, for incommensurable frequencies, a set-up of largely differing frequencies is considered. This way, a strong laser field in the non-perturbative regime assisted by a single highly-energetic -photon is described. Due to the assistance of the latter, a strong enhancement of the total pair-creation rate can be found depending on the laser intensity. Additionally, the influence of the -photon on the angular and energetic distribution of the created particles is investigated, again in the nuclear rest frame and the laboratory frame. Furthermore, the differences arising in the two former cases are directly compared by means of a continuous variation of the laser frequency ratio. This illustrates the strong modifications due to the interference in the commensurable case. Finally, for the special case of two modes with identical frequency, the total pair-creation rate is studied as a function of the ellipticity of the combined laser field. Here, the cases of a constant total field intensity and a constant maximum field intensity are compared.

Background & Aims: Episodic hepatic encephalopathy is frequently precipitated by factors that induce circulatory dysfunction, cause oxidative stress-mediated damage or enhance astrocyte swelling. The administration of albumin could modify these factors and improve the outcome of hepatic encephalopathy. The aim of this study is to assess the efficacy of albumin in a multicenter, prospective, double-blind, controlled trial (ClinicalTrials.gov number, NCT00886925). Methods: Cirrhotic patients with an acute episode of hepatic encephalopathy (grade II-IV) were randomized to receive albumin (1.5 g/kg on day 1 and 1.0 g/kg on day 3) or isotonic saline, in addition to the usual treatment (laxatives, rifaximin 1200 mg per day). The primary end point was the proportion of patients in which encephalopathy was resolved on day 4. The secondary end points included survival, length of hospital stay, and biochemical parameters. Results: Fifty-six patients were randomly assigned to albumin (n = 26) or saline (n = 30) stratified by the severity of HE. Both groups were comparable regarding to demographic data, liver function, and precipitating factors. The percentage of patients without hepatic encephalopathy at day 4 did not differ between both groups (albumin: 57.7% vs. saline: 53.3%; p >0.05). However, significant differences in survival were found at day 90 (albumin: 69.2% vs. saline: 40.0%; p = 0.02). Conclusions: Albumin does not improve the resolution of hepatic encephalopathy during hospitalization. However, differences in survival after hospitalization suggest that the development of encephalopathy may identify a subgroup of patients with advanced cirrhosis that may benefit from the administration of albumin. (C) 2013 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

We construct a simple probit model of the determinants of real house price slump endings. We find that the probability of a house price slump ending is higher, the smaller was the pre-slump house price run-up; the greater has been the cumualtive house price decline; the lower are real mortgage interest rates; and the higher is GDP growth. Slumps are longer, other things being equal, where housing supply is more elastic, but shorter the more developed are financial institutions. For slumps of a given size, shorter sharper slumps are associated with worse macroeconomic performance in the short run, but with better performance in the long run. This suggests that for sufficiently low discount rates, policy makers should not impede the decline in real house prices, and this conclusion is reinforced by the finding that after a certain duration, house price slumps can become self-reinforcing. On the other hand, we also find evidence that during downturns, falling house prices can lead to lower private sector credit flows. Policy makers thus face a delicate balancing act. While they should not intervene to artifically prop up overvalued house prices, they should ensure that their macroeconomic and banking policies are such as to make a bottoming-out more likely. This suggests that they should keep real interest rates low, and ensure that banks are well-capitalised.

Combined on- and offshore wide-angle seismic data were collected in southern Costa Rica along a profile that extends from the Middle America Trench and crosses the Pacific continental margin, the isthmus, and reaches to the Caribbean coast. Closely spaced marine airgun sources were used in the Pacific, coincident with the preexisting seismic reflection line P-1600 recorded by SHELL Int. Four large explosive charges were detonated in boreholdes onshore. The combined interpretation of the near-vertical and wide-angle data provides a detailed crustal model. The profile is located on the northern flank of Cocos Ridge, where we have determined that the subducting oceanic plate has a thickness of 11 to 12 km. It dips down with an average angle of 17° and can be imaged to a depth of at least 35 km with the available data. Erosion of the margin wedge is suggested by a thick low velocity zone overlying the downgoing slab. Like elsewhere along the Middle America Trench, the body of rock underlying forearc and slope sediment has high velocities (>4.0 km/s). At deeper levels (>5 km), the crustal rocks along the profile generally show high velocities (6.0 to 6.6 km/s). To the southwest, these high velocities can be followed to the mid-shelf area. The inverted Térraba Basin contains intermediate velocity sediment (3.0 km/s) with a total thickness of about 2 km. The Limón Basin has up to 6 km of Tertiary and Quaternary sediment. An intracrustal discontinuity is found at a depth of about 18 km, but cannot be determined in detail due to the limited offset of the available data.

Variceal bleeding (VB) is the main cause of death among cirrhotic patients. About 30-50% of early rebleeding is encountered few days after the acute episode of VB. It is necessary to stratify patients with high risk of very early rebleeding (VER) for more aggressive therapies. However, there are few and incompletely understood prognostic models for this purpose.To determine the risk factors associated with VER after an acute VB. Assessment and comparison of a novel prognostic model generated by Classification and Regression Tree Analysis (CART) with classic-used models (MELD and Child-Pugh [CP]).Sixty consecutive cirrhotic patients with acute variceal bleeding. CART analysis, MELD and Child-Pugh scores were performed at admission. Receiver operating characteristic (ROC) curves were constructed to evaluate the predictive performance of the models.Very early rebleeding rate was 13%. Variables associated with VER were: serum albumin (p = 0.027), creatinine (p = 0.021) and transfused blood units in the first 24 hrs (p = 0.05). The area under the ROC for MELD, CHILD-Pugh and CART were 0.46, 0.50 and 0.82, respectively. The value of cut analyzed by CART for the significant variables were: 1) Albumin 2.85 mg/dL, 2) Packed red cells 2 units and 3) Creatinine 1.65 mg/dL the ABC-ROC.Serum albumin, creatinine and number of transfused blood units were associated with VER. A simple CART algorithm combining these variables allows an accurate predictive assessment of VER after acute variceal bleeding. Key words: cirrhosis, variceal bleeding, esophageal varices, prognosis, portal hypertension.

Green tea catechins (GTC) have been shown to inhibit the activities of enzymes involved in folate uptake. Hence, regular green tea drinkers may be at risk of impaired folate status. The present experiments aimed at studying the impact of dietary GTC on folate concentrations and metabolism. In a human pilot study (parallel design) healthy men consumed for 3 weeks 6 capsules (approximately 670 mg GTC) per day (2 capsules with each principal meal) containing aqueous extracts of the leaves of Camellia sinensis (n=17) or placebo (n=16). No differences in plasma folate concentrations were observed between treatments. We further fed groups of 10 male rats diets fortified with 0, 0.05, 0.5, 1, or 5 g GTC/kg for 6 weeks. Only at the highest intake, GTC significantly decreased serum 5-methyl-tetrahydrofolate concentrations in rats, while mRNA concentrations of reduced folate carrier, proton-coupled folate transporter/heme carrier protein 1, and dihydrofolate reductase (DHFR) remained unchanged in intestinal mucosa. Using an in vitro enzyme activity assay, we observed a time- and dose-dependent inhibition of DHFR activity by epigallocatechin gallate and a green tea extract. Our data suggest that regular green tea consumption is unlikely to impair folate status in healthy males, despite the DHFR inhibitory activity of GTC.

[Background & Aims] Non-alcoholic fatty liver disease (NAFLD) has become a major public health problem, but the prevalence of fibrosis associated with non-alcoholic steatohepatitis (NASH) is largely unknown in the general population. This study aimed to provide an updated estimation of the prevalence of NASH fibrosis in Spain., [Methods] This was an observational, retrospective, cross-sectional, population-based study with merged data from two Spanish datasets: a large (N = 12 246) population-based cohort (ETHON), including transient elastography (TE) data, and a contemporary multi-centric biopsy-proven NASH cohort with paired TE data from tertiary centres (N = 501). Prevalence for each NASH fibrosis stage was estimated by crossing TE data from ETHON dataset with histology data from the biopsy-proven cohort., [Results] From the patients with valid TE in ETHON dataset (N = 11 440), 5.61% (95% confidence interval [95% CI]: 2.53-11.97) had a liver stiffness measurement (LSM) ≥ 8 kPa. The proportion attributable to NAFLD (using clinical variables and Controlled Attenuation Parameter) was 57.3% and thus, the estimated prevalence of population with LSM ≥ 8 kPa because of NAFLD was 3.21% (95% CI 1.13–8.75). In the biopsy-proven NASH cohort, 389 patients had LSM ≥ 8 kPa. Among these, 37% did not have significant fibrosis (F2-4). The estimated prevalence of NASH F2-3 and cirrhosis in Spain's adult population were 1.33% (95% CI 0.29–5.98) and 0.70% (95% CI 0.10–4.95) respectively., [Conclusions] These estimations provide an accurate picture of the current prevalence of NASH-related fibrosis in Spain and can serve as reference point for dimensioning the therapeutic efforts that will be required as NASH therapies become available., JC is a receptor of a grant of Fondo Investigaciones Sanitarias (FIS): PI18/01304. Immunomediated Nonalcoholic SteaTohepatItis; prevalence and CharacTerization. INSTInCT.

In non-alcoholic steatohepatitis (NASH), decreased nitric oxide and increased endothelin-1 (ET-1, also known as EDN1) released by sinusoidal endothelial cells (LSEC) induce hepatic stellate cell (HSC) contraction and contribute to portal hypertension (PH). Statins improve LSEC function, and ambrisentan is a selective endothelin-receptor-A antagonist. We aimed to analyse the combined effects of atorvastatin and ambrisentan on liver histopathology and hemodynamics, together with assessing the underlying mechanism in a rat NASH model. Diet-induced NASH rats were treated with atorvastatin (10 mg/kg/day), ambrisentan (30 mg/kg/day or 2 mg/kg/day) or a combination of both for 2 weeks. Hemodynamic parameters were registered and liver histology and serum biochemical determinations analysed. Expression of proteins were studied by immunoblotting. Conditioned media experiments were performed with LSEC. HSCs were characterized by RT-PCR, and a collagen lattice contraction assay was performed. Atorvastatin and ambrisentan act synergistically in combination to completely normalize liver hemodynamics and reverse histological NASH by 75%. Atorvastatin reversed the sinusoidal contractile phenotype, thus improving endothelial function, whereas ambrisentan prevented the contractile response in HSCs by blocking ET-1 response. Additionally, ambrisentan also increased eNOS (also known as Nos3) phosphorylation levels in LSEC, via facilitating the stimulation of endothelin-receptor-B in these cells. Furthermore, the serum alanine aminotransferase of the combined treatment group decreased to normal levels, and this group exhibited a restoration of the HSC quiescent phenotype. The combination of atorvastatin and ambrisentan remarkably improves liver histology and PH in a diet-induced NASH model. By recovering LSEC function, together with inhibiting the activation and contraction of HSC, this combined treatment may be an effective treatment for NASH patients., Summary: Combining atorvastatin with ambrisentan is safe and effective in reducing intrahepatic resistance and portal hypertension in an experimental model of NASH. This liver histology amelioration highlights a promising therapeutic strategy.

Carcinoma hepatocelular; Elastografía transitoria Carcinoma hepatocel·lular; Elastografia transitòria Hepatocellular carcinoma; Transient elastography Background: The potential role of non-invasive tests (NITs) for liver fibrosis for hepatocellular carcinoma (HCC) prediction remains poorly known. Methods: Retrospective analysis of a NAFLD cohort from a single university hospital in Barcelona, Spain. Incidence rates and cumulative incidence for the overall cohort, as well as cirrhotic and non-cirrhotic patients were calculated. Logistic regression analyses were carried out to investigate risk factors of HCC. Results: From the entire cohort of 1040 patients, 996 patients (95.8%) were analyzed, in whom 35 cases of HCC were detected, of which 26 (72.4%) HCC incident cases were newly diagnosed during a median follow-up of 2.5 (1.9–3.6) years. Two-hundred and thirty-one (23.2%) were cirrhotic at baseline. With the exception of 2 (7.7%) cases of HCC, the rest were diagnosed in cirrhotic patients. Overall HCC cumulative incidence was 9.49 (95% CI 6.4–13.9) per 1000 person-years. The incidence rate for cirrhotic patients was 41.2 (95% CI 27.6–61.6) per 1000 person-years and 0.93 (95% CI 0.23–3.7) per 1000 person-years for patients without cirrhosis. Overall mortality was significantly higher amongst patients with HCC (4.4% vs. 30.8%, p < 0.001). In patients with available liver biopsy (n = 249, 25%), advanced fibrosis (F3–F4) was significantly associated with higher HCC incidence, but not steatosis, lobular inflammation, nor ballooning. In the overall cohort, FIB-4 ≥1.3 (HR 8.46, 95% CI 1.06–67.4, p = 0.044) and older age (HR 1.06, 95% CI 1.01–1.11, p = 0.025) were associated with increasing risk of HCC over time, whereas in cirrhotic patients predictors of HCC included decreasing values of albumin (HR 0.34, 95% CI 0.13–0.87, p = 0.024), platelets (HR 0.98, 95% CI 0.98–0.99, p = 0.001), and increasing values of liver stiffness (HR 1.03, 95% CI 1.00–1.06, p = 0.016). Conclusions: In a Spanish cohort of NAFLD patients, HCC was rare in non-cirrhotic patients. NITs might play a relevant role at predicting HCC. The study was conducted in accordance with the Declaration of Helsinki and approved by the Vall d’Hebron University Hospital Campus Institutional Review Board (study protocol code PR(AG)626/2021).

Nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) prevalence has increased in the past two decades, resulting in a significant but under-recognised public health burden. This impacts the prevalence of advanced fibrosis, end-stage liver disease and associated extrahepatic manifestations. To understand the challenges in recognising patients with advanced fibrosis due to NASH and develop a standardised approach to screen these patients, the authors of this document provided their opinions and expertise from practice and published evidence to identify key challenges and current approaches for diagnosing NASH. The severity of liver fibrosis due to NASH is the main indicator of associated morbidity and mortality outcomes. Therefore, identifying patients with, or at risk of, advanced fibrosis due to NASH and linking them to appropriate care is critical. This can be challenging due to a lack of awareness of NASH among healthcare professionals and a lack of standardised protocols for identifying patients. Simple noninvasive tests may provide an opportunity to facilitate early identification of these patients. This article proposes a simple, universally applicable diagnostic algorithm for use in clinical practice, that includes sequential use of noninvasive tests, ideally a biological marker and an imaging technique, which may help to facilitate early diagnosis of these patients. In the opinion of the authors, early detection of advanced fibrosis is fundamental in the efforts to halt the progression of NASH and diagnostic algorithms may facilitate pre-emptive interventions to curtail the disease.