Depositional style and tectonostratigraphic evolution of the El Bierzo Tertiary Subbasin (Pyrenean orogen, NW Spain)

El Bierzo Tertiary sub-basin (Oligocene–Miocene, NW Spain) is a small remnant of the western Duero Basin, a nonmarine broken foreland basin developed in front of the Cantabrian Mountains (Pyrenean orogen). The alluvial infill of El Bierzo Tertiary sub-basin consists of a coarsening-upward succession from fluvial (Toral Formation) to alluvial-fan deposits (Las Médulas Formation) and reflects the uplift of the Cantabrian Mountains, in the north, and then of the related Galaico-Leoneses Mountains, in the south. These alluvial deposits show signs of having been laid down mainly by catastrophic flows (flood-dominated systems) and consist of three main depositional elements, namely, flood-plain fines, and lobe and channel conglomerates and sandstones. The vertical stacking patterns of these deposits and their relationships to the Alpine structures permit to unravel the tectonosedimentary evolution of the basin. The alluvial-plain element is the main constituent of a wide unconfined alluvial plain (Toral Formation) during the early stages of basin evolution, whereas the channel and lobe elements form a set of relatively small, laterally confined alluvial fans (Las Médulas Formation) fed first from the north and then from the south. Las Médulas deposits form two superposed units, the lower unit, cut by the Alpine thrusts, shows a progradational character, and the upper unit, which postdates most of the thrusts but not the youngest ones, displays a composite retrogradational trend. This organisation reflects the interplay between thrust emplacement and alluvial-fan sedimentation and suggests that maximum progradation took place during the climax of Alpine deformation

Concurrent validity of the Alcohol Purchase Task for measuring the reinforcing efficacy of alcohol: an updated systematic review and meta-analysis

Background and aims: An early meta-analysis testing the concurrent validity of the Alcohol Purchase Task (APT), a measure of alcohol''s relative reinforcing value, reported mixed associations, but predated a large number of studies. This systematic review and meta-analysis sought to: (1) estimate the relationships between trait-based alcohol demand indices from the APT and multiple alcohol indicators, (2) test several moderators and (3) analyze small study effects. Methods: A meta-analysis of 50 cross-sectional studies in four databases (n = 18 466, females = 43.32%). Sex, year of publication, number of APT prices and index transformations (logarithmic, square root or none) were considered as moderators. Small study effects were examined by using the Begg–Mazumdar, Egger''s and Duval & Tweedie''s trim-and-fill tests. Alcohol indicators were quantity of alcohol use, number of heavy drinking episodes, alcohol-related problems and hazardous drinking. APT indices were intensity (i.e. consumption at zero cost), elasticity (i.e. sensitivity to increases in costs), Omax (i.e. maximum expenditure), Pmax (i.e. price associated to Omax) and breakpoint (i.e. price at which consumption ceases). Results: All alcohol demand indices were significantly associated with all alcohol-related outcomes (r = 0.132–0.494), except Pmax, which was significantly associated with alcohol-related problems only (r = 0.064). The greatest associations were evinced between intensity in relation to alcohol use, hazardous drinking and heavy drinking and between Omax and alcohol use. All the tested moderators emerged as significant moderators. Evidence of small-study effects was limited. Conclusions: The Alcohol Purchase Task appears to have concurrent validity in alcohol research. Intensity and Omax are the most relevant indices to account for alcohol involvement

TEMPORAL TRENDS OF HEAVY METAL CONCENTRATIONS IN BROWN MACROALGAE FROM COASTAL ENVIRONMENTS

Heavy metals are one of the major drivers of ecological changes in coastal ecosystems. Macroalgae are primary producers of great relevance for ecosystem structure and functioning in these environments, and play a key role in the trophic transfer of these contaminants in the food web. Here, we present the most extensive assessment until now (>3500 records) of heavy metal concentrations in brown macroalgae (Class Phaeophyceae) sampled between 1933 and 2020 worldwide. The study compiles this information from 420 peer reviewed articles to be used as a proxy of global long-term changes in metal concentrations. We report the first detailed multi-decadal time series of Cd, Co, Cr, Cu, Fe, Hg, Mn, Pb and Zn in algae using generalized additive models (GAMs), confirming a significant decrease in metal contamination in the world’s coastal environments since ca. the 1970s for Pb (84% reduction), Zn (79%), Cd (77%) and Cu (72%), since the 1980s for Mn (75%) and Hg (65%), and since the 1990s for Cr (66%), Fe (64%) and Co (60%). Important environmental consequences for the whole aquatic ecosystem, even for human health, may be expected from these changes. The present results provide a building block for the overall evaluation of the status and trends of marine metal contamination, and will help researchers and policy makers to promote new legal regulations and environmental goals against pollution

Prevalence and progression of chronic kidney disease after a liver transplant: a prospective, real-life, observational, two-year multicenter study

Introduction: chronic kidney disease is a frequent complication after liver transplantation. The use of calcineurin inhibitors is one of the causes of this complication. Current immunsuppression regimens that reduce the use of calcineurin inhibitors may be associated with an improved preservation of renal function. Objective: the study aimed to assess the evolution of renal function after liver transplantation in the current routine clinical practice. Methods: an observational, prospective, multicenter study in adult liver transplant recipients was performed. Two hundred and thirty patients with a good renal function before transplantation were assessed six months post-transplantation (baseline) and every six months until month 30. Results: at baseline, 32% of the patients had a reduction in the glomerular filtration rate below < 60 ml/min/1.73 m2. The mean glomerular filtration rate increased from 72.3 to 75.6 ml/min/1.73 m2 at baseline and month 30 respectively (p < 0.01). The mean serum creatinine levels (mg/dl) decreased from 1.13 to 1.09 (p < 0.01). The percentage of patients with stage 3 chronic kidney disease decreased from 31.7% to 26.4%, whereas the percentage of patients with stage 4 remained unchanged (0.4% at baseline and 0.5% at month 30). No patients progressed to end-stage kidney disease that required dialysis or renal transplantation. Conclusion: in the routine clinical practice, a moderate deterioration of renal function is frequent after liver transplantation. However, advanced chronic kidney disease is infrequent in patients with a good pre-transplant renal function

The Treatment With the SGLT2 Inhibitor Empagliflozin Modifies the Hepatic Metabolome of Male Zucker Diabetic Fatty Rats Towards a Protective Profile

[Abstract] The EMPA-REG OUTCOME (Empagliflozin, Cardiovascular Outcome Event Trial in patients with Type 2 Diabetes Mellitus (T2DM)) trial evidenced the potential of sodium-glucose cotransporter 2 (SGLT2) inhibitors for the treatment of patients with diabetes and cardiovascular disease. Recent evidences have shown the benefits of the SGLT2 inhibitor empagliflozin on improving liver steatosis and fibrosis in patients with T2DM. Metabolomic studies have been shown to be very useful to improve the understanding of liver pathophysiology during the development and progression of metabolic hepatic diseases, and because the effects of empagliflozin and of other SGLT2 inhibitors on the complete metabolic profile of the liver has never been analysed before, we decided to study the impact on the liver of male Zucker diabetic fatty (ZDF) rats of a treatment for 6 weeks with empagliflozin using an untargeted metabolomics approach, with the purpose to help to clarify the benefits of the use of empagliflozin at hepatic level. We found that empagliflozin is able to change the hepatic lipidome towards a protective profile, through an increase of monounsaturated and polyunsaturated glycerides, phosphatidylcholines, phosphatidylethanolamines, lysophosphatidylinositols and lysophosphatidylcholines. Empagliflozin also induces a decrease in the levels of the markers of inflammation IL-6, chemerin and chemerin receptor in the liver. Our results provide new evidences regarding the molecular pathways through which empagliflozin could exert hepatoprotector beneficial effects in T2DM.This work was supported by Boehringer Ingelheim Pharma GmbH and Co., by the National Institute of Health “Fondo de Investigaciones Sanitarias del Instituto de Salud Carlos III” Madrid, Spain (PI15/00681, PI17/00409, PI18/00821, PI20/00902, RETICS Programme RD16/0012/0014 and CIBER de Enfermedades Cardiovasculares (CIBERCV)); European Regional Development Fund (FEDER) and European Union framework MSCA-RISE-H2020 Programme (Project number 734899). AH-A was funded by predoctoral research grants from Xunta de Galicia and FPU Program of the Spanish Ministry of Science, Innovation and Universities (Spain); MF-S was funded by the predoctoral research grants “Programa Científico do Centro de Investigación en Medicina Molecular e Enfermidades Crónicas (CiMUS) (Spain) and Xunta de Galicia; and AV-L was funded by the predoctoral research grant from the PFIS Program of the Spanish Ministry of Science and Instituto de Salud Carlos III (Spain

Prognostic value of discharge heart rate in acute heart failure patients: more relevant in atrial fibrillation?

[Abstract] Aims. The prognostic impact of heart rate (HR) in acute heart failure (AHF) patients is not well known especially in atrial fibrillation (AF) patients. The aim of the study was to evaluate the impact of admission HR, discharge HR, HR difference (admission-discharge) in AHF patients with sinus rhythm (SR) or AF on long- term outcomes. Methods. We included 1398 patients consecutively admitted with AHF between October 2013 and December 2014 from a national multicentre, prospective registry. Logistic regression models were used to estimate the association between admission HR, discharge HR and HR difference and one- year all-cause mortality and HF readmission. Results. The mean age of the study population was 72 ± 12 years. Of these, 594 (42.4%) were female, 655 (77.8%) were hypertensive and 655 (46.8%) had diabetes. Among all included patients, 745 (53.2%) had sinus rhythm and 653 (46.7%) had atrial fibrillation. Only discharge HR was associated with one year all-cause mortality (Relative risk (RR) = 1.182, confidence interval (CI) 95% 1.024–1.366, p = 0.022) in SR. In AF patients discharge HR was associated with one year all cause mortality (RR = 1.276, CI 95% 1.115–1.459, p ≤ 0.001). We did not observe a prognostic effect of admission HR or HRD on long-term outcomes in both groups. This relationship is not dependent on left ventricular ejection fraction. Conclusions. In AHF patients lower discharge HR, neither the admission nor the difference, is associated with better long-term outcomes especially in AF patients

Fatigue in Women with Fibromyalgia: A Gene-Physical Activity Interaction Study

Fatigue is a cardinal symptom in fibromyalgia. Fatigue is assumed to be the result of genetic susceptibility and environmental factors. We aimed at examining the role of genetic susceptibility for fatigue in southern Spanish women with fibromyalgia, by looking at single nucleotide polymorphisms in 34 fibromyalgia candidate-genes, at the interactions between genes, and at the gene-physical activity interactions. We extracted DNA from saliva of 276 fibromyalgia women to analyze gene-polymorphisms. Accelerometers registered physical activity and sedentary behavior. Fatigue was assessed with the Multidimensional Fatigue Inventory. Based on the Bonferroni's and False Discovery Rate values, we found that the genotype of the rs4453709 polymorphism (sodium channel protein type 9 subunit alpha, SCN9A, gene) was related to reduced motivation (AT carriers showed the highest reduced motivation) and reduced activity (AA carriers showed the lowest reduced activity). Carriers of the heterozygous genotype of the rs1801133 (methylene tetrahydrofolate reductase, MTHFR, gene) or rs4597545 (SCN9A gene) polymorphisms who were physically active reported lower scores on fatigue compared to their inactive counterparts. Highly sedentary carriers of the homozygous genotype of the rs7607967 polymorphism (AA/GG genotype; SCN9A gene) presented more reduced activity (a dimension of fatigue) than those with lower levels of sedentary behavior. Collectively, findings from the present study suggest that the contribution of genetics and gene-physical activity interaction to fatigue in fibromyalgia is modest

Serum Potassium Dynamics During Acute Heart Failure Hospitalization

[Abstract] Background. Available information about prognostic implications of potassium levels alteration in the setting of acute heart failure (AHF) is scarce. Objectives. We aim to describe the prevalence of dyskalemia (hypo or hyperkalemia), its dynamic changes during AHF-hospitalization, and its long-term clinical impact after hospitalization. Methods. We analyzed 1779 patients hospitalized with AHF who were included in the REDINSCOR II registry. Patients were classified in three groups, according to potassium levels both on admission and discharge: hypokalemia (potassium  5 mEq/L). Results. The prevalence of hypokalemia and hyperkalemia on admission was 8.2 and 4.6%, respectively, and 6.4 and 2.7% at discharge. Hyperkalemia on admission was associated with higher in-hospital mortality (OR = 2.32 [95% CI: 1.04–5.21] p = 0.045). Among patients with hypokalemia on admission, 79% had normalized potassium levels at discharge. In the case of patients with hyperkalemia on admission, 89% normalized kalemia before discharge. In multivariate Cox regression, dyskalemia was associated with higher 12-month mortality, (HR = 1.48 [95% CI, 1.12–1.96], p = 0.005). Among all patterns of dyskalemia persistent hypokalemia (HR = 3.17 [95% CI: 1.71–5.88]; p < 0.001), and transient hyperkalemia (HR = 1.75 [95% CI: 1.07–2.86]; p = 0.023) were related to reduced 12-month survival. Conclusions. Potassium levels alterations are frequent and show a dynamic behavior during AHF admission. Hyperkalemia on admission is an independent predictor of higher in-hospital mortality. Furthermore, persistent hypokalemia and transient hyperkalemia on admission are independent predictors of 12-month mortality.This work is funded by the Instituto de Salud Carlos III (Ministry of Economy, Industry, and Competitiveness) and co-funded by the European Regional Development Fund, through the CIBER in cardiovascular diseases (CB16/11/00502)