Dynamics of suspended sediment borne persistent organic pollutants in a large regulated Mediterranean river (Ebro, NE Spain)

Mediterranean rivers are characterized by highly variable hydrological regimes that are strongly dependent on the seasonal rainfall. Sediment transport is closely related to the occurrence of flash-floods capable to deliver enough kinetic energy to mobilize the bed and channel sediments. Contaminants accumulated in the sediments are likely to be mobilized as well during such events. However, whereas there are many studies characterizing contaminants in steady sediments, those devoted to the transport dynamics of suspended-sediment borne pollution are lacking. Here we examined the occurrence and transport of persistent organic microcontaminants present in the circulating suspended sediments during a controlled flushing flow in the low part of the River Ebro (NE Spain) 12km downstream of a well-known contaminated hot-spot associated to a nearby chloro-alkali industry. Polycyclic aromatic hydrocarbons (PAHs) and semi-volatile organochlorine pollutants (DDT and related compounds, DDX; polychlorinated byphenils, PCBs; and other organochlorine compound, OCs) were measured in the particulate material by GC-MS and GC-MS/MS, using previously developed analytical methods. The concentration levels observed were compared to previously reported values in steady sediments in the same river and discussed on a regulatory perspective. Hydrographs and sedigraphs recorded showed a peak-flow of 1300m3s-1 and a corresponding peak of suspended sediments of 315mgL-1. Combination of flow discharge, suspended sediments and pollutants' concentrations data allowed for quantifying the mass flows (mass per unit of time) and setting the load budgets (weight amount) of the different pollutants transported by the river during the monitored event. Mean mass-flows and total load values found were 20.2mgs-1 (400g) for PAHs, 38mgs-1 (940g) for DDX, 44mgs-1 (1038g) for PCBs and 8mgs-1 (200g) for OCs. The dynamic pattern behavior of PAHs differs substantially to that of organochlorine pollutants, thus reflecting different pollution origins.This work was supported by the Spanish Ministry of Economy and Competitiveness through the Consolider-Ingenio 2010 project SCARCE (CSD2009-00065) and by the Generalitat de Catalunya (Consolidated Research Group: Water and Soil Quality Unit 2009-SGR-965). The research leading to these results has received funding from the European Comunities 7th Framework Programme under Grant Agreement No. 603629-ENV-2013-6.2.1-Globaqua.Peer reviewe

Taxonomical and nomenclatural notes in the genus Cheirolophus Cass. (Asteraceae, Centaureinae)

Es lectotipifica i es reivindica el valor taxonòmic de Cheirolophus cavanillesianus nomo nov. [Centaurea virgata Cav., sinònim reemplaçat, syn. subst.) (Asteraceae, Centaureinae), espècie descrita per A. J. Cavanilles el 1795 per a la província d'Alacant. Dins d'aquest taxon, incloem a nivell subespecífic la varietat capillifolius [Ch. cavanillesianus subsp. capillifolius, combo & stat. nov.), taxon indicat per a diverses localitats de la província d'Alacant. Així mateix, es realitza la lectotipificació de Ch. intybaceus (Lam.) Dostál.We propose the lectotypification as well as the taxonomic value for Cheirolophus cavanillesianus nomo nov. [Centaurea virgata Cav., replaced synonym, syn. subst.) (Asteraceae, Centaureinae), a plant species described by A. J. Cavanilles in 1795 for the province of Alicante. Within this taxon we raise up to the subspecies level the variety capillifolius [Ch. cavanillesianus subsp. capillifolius, combo & stat. nov.), taxa indicated for sorne populations of the Alicante coast. Moreover, Ch. intybaceus (Lam.) Dostál has also been lectotypified

c-Jun N-terminal kinase phosphorylation is a biomarker of plitidepsin activity

Plitidepsin is an antitumor drug of marine origin currently in Phase III clinical trials in multiple myeloma. In cultured cells, plitidepsin induces cell cycle arrest or an acute apoptotic process in which sustained activation of c-Jun N-terminal kinase (JNK) plays a crucial role. With a view to optimizing clinical use of plitidepsin, we have therefore evaluated the possibility of using JNK activation as an in vivo biomarker of response. In this study, we show that administration of a single plitidepsin dose to mice xenografted with human cancer cells does indeed lead to increased phosphorylation of JNK in tumors at 4 to 12 h. By contrast, no changes were found in other in vitro plitidepsin targets such as the levels of phosphorylated-ERK, -p38MAPK or the protein p27KIP1. Interestingly, plitidepsin also increased JNK phosphorylation in spleens from xenografted mice showing similar kinetics to those seen in tumors, thereby suggesting that normal tissues might be useful for predicting drug activity. Furthermore, plitidepsin administration to rats at plasma concentrations comparable to those achievable in patients also increased JNK phosphorylation in peripheral mononuclear blood cells. These findings suggest that changes in JNK activity provide a reliable biomarker for plitidepsin activity and this could be useful for designing clinical trials and maximizing the efficacy of plitidepsin.This work has been partially supported by grants (Programa Cenit, CEN-20091016, SAF2010-18302 and Fondo Europeo de Desarrollo Regional-Instituto de Salud Carlos III, RD12/0036/0021) from Ministerio de Economíay Competitividad of Spain.S

Osteoporosis en alcoholismo crónico : un problema infravalorado. Incidencia y complicaciones de las fracturas en el paciente alcohólico

Main goal. To estimate the incidence of pathologic fractures and associated complications in patients in follow-up for moderate to severe chronic alcoholism by the Unidad de Conductas Adictivas (UCA) of our health area. To highlight the importance of recognizing osteoporosis in patients with chronic alcoholism in order to establish strategies for prevention of both primary and secondary fractures. Material and methods. Retrospective analysis of patients in follow-up for chronic alcoholism by the UCA between 2014 and 2018 that required assessment by the Orthopedics Unit for fractures during that period, excluding fractures in the context of politraumatism. In addition, the complications derived from these fractures were collected and it was determined whether bone densitometry (BMD) was indicated following the main osteoporosis guidelines. Results. The incidence rate of fractures due to low-energy trauma in the selected population during the follow-up period was 7.2 for every 1,000 patients / year. 41% of the 44 study patients suffered new fractures during this period. 33% of the patients with fractures that required surgical treatment suffered major complications. 100% of the patients fulfilled criteria for BMD after the first traumatic event, despite only 20% of them being ultimately performed. Conclusions. The prevalence of fractures and associated complications in alcoholic patients is significantly higher than in the general population. It is necessary to stress the importance of both primary and secondary prevention of pathologic fractures in alcoholic patients, and if they occur, osteosynthesis techniques adapted to an osteoporotic bone should be applied

Tween 80 Improves the Acid-Fast Bacilli Quantification in the Magnetic Nanoparticle-Based Colorimetric Biosensing Assay (NCBA)

Despite its reduced sensitivity, sputum smear microscopy (SSM) remains the main diagnostic test for detecting tuberculosis in many parts of the world. A new diagnostic technique, the magnetic nanoparticle-based colorimetric biosensing assay (NCBA) was optimized by evaluating different concentrations of glycan-functionalized magnetic nanoparticles (GMNP) and Tween 80 to improve the acid-fast bacilli (AFB) count. Comparative analysis was performed on 225 sputum smears: 30 with SSM, 107 with NCBA at different GMNP concentrations, and 88 with NCBA-Tween 80 at various concentrations and incubation times. AFB quantification was performed by adding the total number of AFB in all fields per smear and classified according to standard guidelines (scanty, 1+, 2+ and 3+). Smears by NCBA with low GMNP concentrations (≤1.5 mg/mL) showed higher AFB quantification compared to SSM. Cell enrichment of sputum samples by combining NCBA-GMNP, incubated with Tween 80 (5%) for three minutes, improved capture efficiency and increased AFB detection up to 445% over SSM. NCBA with Tween 80 offers the opportunity to improve TB diagnostics, mainly in paucibacillary cases. As this method provides biosafety with a simple and inexpensive methodology that obtains results in a short time, it might be considered as a point-of-care TB diagnostic method in regions where resources are limited

Efficacy and safety of givosiran for acute hepatic porphyria: Final results of the randomized phase III ENVISION trial

Background & Aims: Acute hepatic porphyria (AHP) is caused by defects in hepatic heme biosynthesis, leading to disabling acute neurovisceral attacks and chronic symptoms. In ENVISION (NCT03338816), givosiran treatment for 6 months reduced attacks and other disease manifestations, compared with placebo. Here we report data from the 36-month final analysis of ENVISION. Methods: Ninety-four patients with AHP (age ≥12 years) and recurrent attacks were randomized 1:1 to monthly double-blind subcutaneous givosiran 2.5 mg/kg (N=48) or placebo (N=46) for 6 months. In the open-label extension (OLE) period, 93 patients received givosiran 2.5 or 1.25 mg/kg for 6 months or more before transitioning to 2.5 mg/kg. Endpoints were exploratory unless otherwise noted. Results: During givosiran treatment, median annualized attack rate (AAR) was 0.4. Through Month 36, annualized days of hemin use remained low in the continuous givosiran group (median, 0.0 to 0.4) and decreased in the placebo crossover group (16.2 to 0.4). At end of OLE, in the continuous givosiran and placebo crossover groups, 86% and 92%, respectively, had 0 attacks. AAR was lower than historical AAR in 98% and 100%, respectively (post hoc analysis), and there were 0 days of hemin use in 88% and 90%, respectively. The 12-item Short Form Health Survey physical and mental component scores increased by 8.6 and 8.1, respectively (continuous givosiran) and 9.4 and 3.2, respectively (placebo crossover). EQ-5D health-related questionnaire scores increased by 18.9 (continuous givosiran) and 9.9 (placebo crossover). Lowering of urinary delta-aminolevulinic acid and porphobilinogen levels was sustained. Safety findings demonstrated a continued positive risk/benefit profile for givosiran

Enhanced superconductivity in atomically thin TaS2

The ability to exfoliate layered materials down to the single layer limit has presented the opportunity to understand how a gradual reduction in dimensionality affects the properties of bulk materials. Here we use this top-down approach to address the problem of superconductivity in the two-dimensional limit. The transport properties of electronic devices based on 2H tantalum disulfide flakes of different thicknesses are presented. We observe that superconductivity persists down to the thinnest layer investigated (3.5 nm), and interestingly, we find a pronounced enhancement in the critical temperature from 0.5 to 2.2 K as the layers are thinned down. In addition, we propose a tight-binding model, which allows us to attribute this phenomenon to an enhancement of the effective electron-phonon coupling constant. This work provides evidence that reducing the dimensionality can strengthen superconductivity as opposed to the weakening effect that has been reported in other 2D materials so far

Recombinant human leptin treatment in genetic lipodystrophic syndromes: the long-term Spanish experience

Lipodystrophies are a group of diseases mainly characterized by a loss of adipose tissue and frequently associated with insulin resistance, hypertriglyceridemia, and hepatic steatosis. In uncommon lipodystrophies, these complications frequently are difficult to control with conventional therapeutic approaches. This retrospective study addressed the effectiveness of recombinant methionyl leptin (metreleptin) for improving glucose metabolism, lipid profile, and hepatic steatosis in patients with genetic lipodystrophic syndromes. We studied nine patients (five females and four males) with genetic lipodystrophies [seven with Berardinelli-Seip syndrome, one with atypical progeroid syndrome, and one with type 2 familial partial lipodystrophy (FPLD)]. Six patients were children under age 9 years, and all patients had baseline triglycerides levels >2.26 mmol/L and hepatic steatosis; six had poorly controlled diabetes mellitus. Metreleptin was self-administered subcutaneously daily at a final dose that ranged between 0.05 and 0.24 mg/(kg day) [median: 0.08 mg/(kg day)] according to the body weight. The duration of treatment ranged from 9 months to 5 years, 9 months (median: 3 years). Plasma glucose, hemoglobin A1c (Hb A1c), lipid profile, plasma insulin and leptin, and hepatic enzymes were evaluated at baseline and at least every 6 months. Except for the patient with FPLD, metreleptin replacement significantly improved metabolic control (Hb A1c: from 10.4 to 7.1 %, p < 0.05). Plasma triglycerides were reduced 76 % on average, and hepatic enzymes decreased more than 65 %. This study extends knowledge about metreleptin replacement in genetic lipodystrophies, bearing out its effectiveness for long periods of time

Cross-communication between Gi and Gs in a G-protein-coupled receptor heterotetramer guided by a receptor C-terminal domain

BACKGROUND: G-protein-coupled receptor (GPCR) heteromeric complexes have distinct properties from homomeric GPCRs, giving rise to new receptor functionalities. Adenosine receptors (A1R or A2AR) can form A1R-A2AR heteromers (A1-A2AHet), and their activation leads to canonical G-protein-dependent (adenylate cyclase mediated) and -independent (β-arrestin mediated) signaling. Adenosine has different affinities for A1R and A2AR, allowing the heteromeric receptor to detect its concentration by integrating the downstream Gi- and Gs-dependent signals. cAMP accumulation and β-arrestin recruitment assays have shown that, within the complex, activation of A2AR impedes signaling via A1R. RESULTS: We examined the mechanism by which A1-A2AHet integrates Gi- and Gs-dependent signals. A1R blockade by A2AR in the A1-A2AHet is not observed in the absence of A2AR activation by agonists, in the absence of the C-terminal domain of A2AR, or in the presence of synthetic peptides that disrupt the heteromer interface of A1-A2AHet, indicating that signaling mediated by A1R and A2AR is controlled by both Gi and Gs proteins. CONCLUSIONS: We identified a new mechanism of signal transduction that implies a cross-communication between Gi and Gs proteins guided by the C-terminal tail of the A2AR. This mechanism provides the molecular basis for the operation of the A1-A2AHet as an adenosine concentration-sensing device that modulates the signals originating at both A1R and A2AR