Towards circular and sustainable restoration of a deeply polluted river basin: The Odiel River catchment (SW Spain)

The Ría de Huelva estuary located in SW Spain is heavily polluted by acid mine drainage leachates and phosphate fertilizer industry effluents. This study assesses the effectiveness of a solid waste rich in calcite originated during the remediation of industrial effluents using the passive dispersed alkaline substrate (DAS) technology, for the treatment of highly acid and polluted mine drainages. The research consists of flowing the mine leachates through a column loaded with a combination of an alkaline reagent (i.e., calcite-rich waste resulting from the treatment of industrial leachates) scattered in a non-reactive matrix (i.e., wood chips) to increase the pH of acidic water while decreasing the solubility of dissolved pollutants. The alkaline treatment achieved average removal percentages of 100 % for Al and Fe, and close to 90 % for Cu. However, the treatment was not effective for other metals present in mine drainages such as Co and Ni. These results are comparable to those achieved in the DAS treatment with commercial limestone. The precipitation of oxyhydroxysulfates (i.e., schwertmannite and basaluminite) and carbonates (i.e., malachite and hydrozincite) minerals could be controlling the solubility of pollutants during the treatment. The solid wastes from the DAS treatment were subjected to two standardized leaching tests (EN 12457-2 from the European Union and toxicity characteristic leaching procedure (TCLP) from the United States) in order to ensure suitable management and avoid potential environmental impacts. According to European Union legislation, the high mobility of Cu, Zn and SO4 confers some solid wastes from the DAS treatment the hazardous waste classification. However, according to United States regulation, these same solids are considered non-hazardous wastes. This research could help to improve the environmental sustainability of acid mine drainage treatment with DAS technology by replacing marketable limestone with a low-cost alkaline waste.13 página

High-resolution temporal monitoring of rare earth elements in acidic drainages from an abandoned sulphide mine (iberian pyrite belt, Spain)

Rare earth elements (REE) are strategic elements due to their economic importance. However, the studies dedicated to the distribution and behaviour of REE in aquatic systems have been scarce until a few decades ago. This work studies the seasonal variations of REE concentrations in acid mine drainage (AMD) affected water courses and the factors controlling their mobility under different hydrological conditions. To address this issue, a high-resolution sampling was performed for two years in selected sampling sites. REE concentrations were very high (median values of 2.7–3.4 mg/L, maximum of 7.0 mg/L). These values are several orders of magnitude higher than those found in natural waters, highlighting the importance of AMD processes on the release of REE to the hydrosphere. No good correlations were found between pH and REE concentration, while REE correlated positively (r Spearman coefficient of 0.78–0.94) with EC and negatively (r −0.88 to −0.90) with discharge in AMD-affected streams. A conservative behaviour of REE was observed due to the strongly acidic conditions observed in the study area. The waters also showed an enrichment in MREEs over LREEs and HREEs (mean values of GdN/LaN>1.8 and YbN/GdN < 0.7), typical of AMD waters. An asymmetry in the content of LREE and HREE was observed in AMD samples studied, which could be explained by the preferential dissolution of LREE or HREE-enriched minerals within each waste heaps. Multivariate analysis suggests the influence of Mn-rich minerals existent in the study area as a potential source of LREE

Chemical profiling and cholinesterase inhibitory activity of five Phaedranassa Herb. (Amaryllidaceae) species from Ecuador

It is estimated that 50 million people in the world live with dementia, 60-70% of whom suffer from Alzheimer's disease (AD). Different factors are involved in the development of AD, including a reduction in the cholinergic neurotransmission level. The Amaryllidaceae plant family contains an exclusive, large, and still understudied alkaloid group characterized by a singular skeleton arrangement and a broad spectrum of biological activities. The chemistry and biodiversity of Ecuadorian representatives of the Phaedranassa genus (Amaryllidaceae) have not been widely studied. In this work, five Ecuadorian Phaedranassa species were examined in vitro for their activity towards the enzymes acetyl- (AChE) and butyrylcholinesterase (BuChE), and the alkaloid profile of bulb extracts was analyzed by GC-MS. The species Phaedranassa cuencana and Phaedranassa dubia showed the most AChE and BuChE inhibitory activity, respectively. To obtain insight into the potential role of the identified alkaloids in these inhibitory effects, docking experiments were carried out, and cantabricine showed in silico inhibitory activity against both cholinesterase structures. Our results show that Amaryllidaceae species from Ecuador are a potential source of new drugs for the palliative treatment of AD

Synthesis and Antiproliferative Activity of 3 and 7-Styrylcoumarins

A series of styrylcoumarins were obtained via Mizoroki-Heck reactions between 3-bromo-4-methyl7-(octyloxy)-2H-chromen-2-one or 2-oxo-2H-chromen-7-yl trifluoromethanesulfonate and functionalized styrenes. The structures of the products were elucidated by spectroscopic analysis. All compounds were evaluated against SW480 and CHO-K1 cell lines. A number of hybrids showed good antiproliferative activity. Among the tested compounds, hybrids 6e, 10c and 10d, exhibited the highest activity (IC50- SW480/48h = 6,92; 1,01 and 5,33 µM, respectively) and selectivity (IS48h = >400; 67,8 and 7,2, respectively). In addition, these compounds were able to preserve their activities over time. The results achieved by these hybrids were even better than the lead compounds (coumarin and resveratrol) and the standard drug (5-FU). As regards structure-activity relationship it seems that the location of the styryl group on the coumarin structure and the presence of the hydroxyl group on the phenyl ring were determinant for the activity

Splicing Machinery is Dysregulated in Pituitary Neuroendocrine Tumors and is Associated with Aggressiveness Features

Pituitary neuroendocrine tumors (PitNETs) constitute approximately 15% of all brain tumors, and most have a sporadic origin. Recent studies suggest that altered alternative splicing and, consequently, appearance of aberrant splicing variants, is a common feature of most tumor pathologies. Moreover, spliceosome is considered an attractive therapeutic target in tumor pathologies, and the inhibition of SF3B1 (e.g., using pladienolide-B) has been shown to exert antitumor effects. Therefore, we aimed to analyze the expression levels of selected splicing-machinery components in 261 PitNETs (somatotropinomas/non-functioning PitNETS/corticotropinomas/prolactinomas) and evaluated the direct effects of pladienolide-B in cell proliferation/viability/hormone secretion in human PitNETs cell cultures and pituitary cell lines (AtT-20/GH3). Results revealed a severe dysregulation of splicing-machinery components in all the PitNET subtypes compared to normal pituitaries and a unique fingerprint of splicing-machinery components that accurately discriminate between normal and tumor tissue in each PitNET subtype. Moreover, expression of specific components was associated with key clinical parameters. Interestingly, certain components were commonly dysregulated throughout all PitNET subtypes. Finally, pladienolide-B reduced cell proliferation/viability/hormone secretion in PitNET cell cultures and cell lines. Altogether, our data demonstrate a drastic dysregulation of the splicing-machinery in PitNETs that might be associated to their tumorigenesis, paving the way to explore the use of specific splicing-machinery components as novel diagnostic/prognostic and therapeutic targets in PitNETs

In1-ghrelin splicing variant is overexpressed in pituitary adenomas and increases their aggressive features

Pituitary adenomas comprise a heterogeneous subset of pathologies causing serious comorbidities, which would benefit from identification of novel, common molecular/cellular biomarkers and therapeutic targets. The ghrelin system has been linked to development of certain endocrine-related cancers. Systematic analysis of the presence and functional implications of some components of the ghrelin system, including native ghrelin, receptors and the recently discovered splicing variant In1-ghrelin, in human normal pituitaries (n 5 11) and pituitary adenomas (n 5 169) revealed that expression pattern of ghrelin system suffers a clear alteration in pituitary adenomasas comparedwith normal pituitary, where In1-ghrelin is markedly overexpressed. Interestingly, in cultured pituitary adenoma cells In1-ghrelin treatment (acylated peptides at 100 nM; 24–72 h) increasedGHandACTHsecretion, Ca21 and ERK1/2 signaling and cell viability, whereas In1-ghrelin silencing (using a specific siRNA; 100 nM) reduced cell viability. These results indicate that an alteration of the ghrelin system, specially its In1-ghrelin variant, could contribute to pathogenesis of different pituitary adenomas types, and suggest that this variant and its related ghrelin system could provide new tools to identify novel, more general diagnostic, prognostic and potential therapeutic targets in pituitary tumors

White Paper 4: Challenges In Biomedicine & Health

Publicado en Madrid, 231 p. ; 17 cm.A lesson that we have learned from the pandemia caused by coronavirus is that solutions in health require coordinated actions. Beside this and other emerging and re-emerging infectious diseases, millions of Europeans are suffering a plethora of disorders that are currently acquiring epidemic dimensions, including cancer, rare diseases, pain and food allergies, among others. New tools for prevention, diagnosis and treatment need to be urgently designed and implemented using new holistic and multidisciplinary approaches at three different levels (basic research, translational/clinical and public/social levels) and involving researchers, clinicians, industry and all stakeholders in the health system. The CSIC is excellently positioned to lead and coordinate these challenges in Biomedicine and Health.Peer reviewe

Monitorización de la frecuencia cardíaca en las labores de extinción de incendios forestales, para la prevención de riesgos laborales

P. 6-26Ante la previsión de aumento de incendios forestales en la zona meditarránea,TRAGSA y la Fraternidad Muprespa analizan los aspectos derivados de la frecuencia cardiaca en las labores de extinción de incendios forestales. El trabajo físico del personal especialista en extinción de incendios forestales durante la extinción de incendios se realiza a una intensidad de esfuerzo que es lo suficientemente alta como para conllevar un elevado coste energético, y que se corresponde a una carga de trabajo que requiere y exige una buena condición física para afrontarla con las suficientes garantías y con el menor riesgo para la salud.N

A controlled trial of rivaroxaban after transcatheter aortic-valve replacement

Background: whether the direct factor Xa inhibitor rivaroxaban can prevent thromboembolic events after transcatheter aortic-valve replacement (TAVR) is unclear. Methods: we randomly assigned 1644 patients without an established indication for oral anticoagulation after successful TAVR to receive rivaroxaban at a dose of 10 mg daily (with aspirin at a dose of 75 to 100 mg daily for the first 3 months) (rivaroxaban group) or aspirin at a dose of 75 to 100 mg daily (with clopidogrel at a dose of 75 mg daily for the first 3 months) (antiplatelet group). The primary efficacy outcome was the composite of death or thromboembolic events. The primary safety outcome was major, disabling, or life-threatening bleeding. The trial was terminated prematurely by the data and safety monitoring board because of safety concerns. Results: after a median of 17 months, death or a first thromboembolic event (intention-to-treat analysis) had occurred in 105 patients in the rivaroxaban group and in 78 patients in the antiplatelet group (incidence rates, 9.8 and 7.2 per 100 person-years, respectively; hazard ratio with rivaroxaban, 1.35; 95% confidence interval [CI], 1.01 to 1.81; P = 0.04). Major, disabling, or life-threatening bleeding (intention-to-treat analysis) had occurred in 46 and 31 patients, respectively (4.3 and 2.8 per 100 person-years; hazard ratio, 1.50; 95% CI, 0.95 to 2.37; P = 0.08). A total of 64 deaths occurred in the rivaroxaban group and 38 in the antiplatelet group (5.8 and 3.4 per 100 person-years, respectively; hazard ratio, 1.69; 95% CI, 1.13 to 2.53). Conclusions: in patients without an established indication for oral anticoagulation after successful TAVR, a treatment strategy including rivaroxaban at a dose of 10 mg daily was associated with a higher risk of death or thromboembolic complications and a higher risk of bleeding than an antiplatelet-based strategy. (Funded by Bayer and Janssen Pharmaceuticals; GALILEO ClinicalTrials.gov number, NCT02556203.)