CD44-high neural crest stem-like cells are associated with tumour aggressiveness and poor survival in neuroblastoma tumours

BACKGROUND: Neuroblastoma is a paediatric tumour originated from sympathoadrenal precursors and characterized by its heterogeneity and poor outcome in advanced stages. Intra-tumoral cellular heterogeneity has emerged as an important feature in neuroblastoma, with a potential major impact on tumour aggressiveness and response to therapy. CD44 is an adhesion protein involved in tumour progression, metastasis and stemness in different cancers; however, there has been controversies about the significance of CD44 expression in neuroblastoma and its relationship with tumour progression. METHODS: We have performed transcriptomic analysis on patient tumour samples studying the outcome of patients with high CD44 expression. Adhesion, invasion and proliferation assays were performed in sorted CD44high neuroblastoma cells. Tumoursphere cultures have been used to enrich in undifferentiated stem-like cells and to asses self-renewal and differentiation potential. We have finally performed in vivo tumorigenic assays on cell line-derived or Patient-derived xenografts. FINDINGS: We show that high CD44 expression is associated with low survival in high-grade human neuroblastoma, independently of MYCN amplification. CD44 is expressed in a cell population with neural crest stem-like features, and with the capacity to generate multipotent, undifferentiated tumourspheres in culture. These cells are more invasive and proliferative in vitro. CD44 positive cells obtained from tumours are more tumorigenic and metastatic, giving rise to aggressive neuroblastic tumours at high frequency upon transplantation. INTERPRETATION: We describe an unexpected intra-tumoural heterogeneity within cellular entities expressing CD44 in neuroblastoma, and propose that CD44 has a role in neural crest stem-like undifferentiated cells, which can contribute to tumorigenesis and malignancy in this type of cancer. FUNDING: Research supported by grants from the "Asociación Española contra el Cáncer" (AECC), the Spanish Ministry of Science and Innovation SAF program (SAF2016-80412-P), and the European Research Council (ERC Starting Grant to RP).Spanish Ministry of Science and Innovation SAF program (SAF2016-80412-P

Is aided phytostabilization a suitable technique for the remediation of tailings?

Mining activity in Cartagena-La Union mining district (SE Spain) dates back more than 2500 years. Consequently, large amounts of sterile materials with large metal(loid) contents (mostly Zn and Pb) have accumulated in tailings ponds. A reclamation strategy based on aided phytostabilization was carried out to reclaim one tailings pond to reduce environmental and public health hazards. The main goal of this study was to determine the effectiveness of the aided phytostabilization strategy after 30 months from its implementation in enhancing soil quality and fertility and reducing mobility of the metals. Marble waste, raw pig slurry and its solid phase after physical separation were applied as amendments, and 13 Mediterranean native plant species were planted or sown. Various soil physicochemical and biochemical properties, together with the pseudo-total and bioavailable fraction of the metal(loid)s, As, Cd, Cu, Pb and Zn, were monitored for 30 months. Results showed that pH, total organic carbon (TOC), total nitrogen (TN), cation exchange capacity (CEC), available phosphorus (P), exchangeable potassium (K), microbial biomass carbon (MBC), basal soil respiration (BSR) and enzyme activities increased with the application of the amendments and development of vegetation. In addition, the available fraction of metals markedly decreased (90–99%). Most plant species present in the area did not transfer large amounts of trace elements to the aerial tissues. The roots of Lygeum spartum loefl. Ex L. and Piptatherum miliaceum (L.) Coss. accumulated the largest amounts of As, Pb and Zn. Thus, the application of marble waste to increase pH and immobilize metal(loid)s, and pig slurry as a source of organic matter and nutrients, together with the development of vegetation to immobilize metal(loid)s in the roots and rhizosphere, and the effect of microbial communities on organic matter stabilization and development, have contributed to improve soil quality and fertility. Once the soil quality of mine tailings was improved, the development of vegetation and microbial colonization increased, promoting integrated reclamation of the area. Therefore, aided phytostabilization was a suitable technique for remediation of this tailings pond.European Commission, Grant/Award Number: Life project; European Union LIFE+ project MIPOLARE, Grant/Award Number: LIFE09 ENV/ES/00043

Preparation and Characterization of Resveratrol Loaded Pectin/Alginate Blend Gastro-Resistant Microparticles

Background: The use of resveratrol as a dietary supplement is limited because it is easily oxidized and, after oral ingestion, it is metabolized into enterocytes and hepatocytes. Thus, new formulations are needed in order to improve its oral bioavailability. Objective: The objective of this study was to develop and characterize a gastro-resistant formulation of resveratrol for oral administration as a dietary supplement. Method: Resveratrol was encapsulated in Eudragit-coated pectin-alginate microparticles. Results: The microparticle size was about 1450 mu m, with an encapsulation efficiency of 41.72% +/- 1.92%. The dissolution assay conducted, as specified in the European Pharmacopoeia for delayed-release dosage forms, revealed that our microparticles were gastro-resistant, because the resveratrol percentage released from microparticles in acid medium was less than 10%. In addition, the high-performance liquid chromatographic (HPLC) method developed for resveratrol content quantification in the microparticles was validated according to International Council for Harmonisation (ICH) Q2 (R1) guidelines. Finally, the biological activity of resveratrol was investigated in 3T3-L1 mature adipocytes, concluding that the encapsulation process does not affect the activity of resveratrol. Conclusion: In summary, the gastro-resistant microparticles developed could represent a suitable method of including resveratrol in dietary supplements and in functional foods used in obesity therapy.This research was partially funded by the Basque Government (Consolidated Groups, IT-407-07; IT-572-13; SAIOTEK SA-2011-00118) and the Spanish Government (INNPACTO, IPT-2012-0602-300000, 2012). The authors gratefully acknowledge the support provided by the University of the Basque Country UPV/EHU (UFI11/32)

Desarrollo de panuveítis por tuberculosis en paciente con esclerosis múltiple tratado con interferón beta

ResumenPresentamos el caso de un ex toxicómano de 50 años que acudió a consulta de oftalmología con visión borrosa bilateral. En la anamnesis refería su desintoxicación 20 años atrás, con abstinencia total desde entonces y buena reinserción social. Su historia clínica reflejaba serología de hepatitis B+ y C+, pero VIH− y recientemente comenzó con esclerosis múltiple, controlada con interferón beta. Señalaba haber padecido últimamente un resfriado invernal prolongado.En la exploración oftalmológica se apreciaba una uveítis bilateral con precipitados queráticos. En funduscopia del ojo derecho destacaban múltiples granulomas coroideos y zonas de vasculitis periférica, activas y cicatriciales. La funduscopia del ojo izquierdo era normal.Tras diversas pruebas diagnósticas, como radiografía torácica y TAC pulmonar, se detectaron varios nódulos pulmonares. Asimismo, se realizó una prueba de Mantoux que resultó fuertemente positiva. La analítica mostraba neutropenia y linfopenia importantes. Por todo ello se hizo un diagnóstico de presunción de panuveítis secundaria a tuberculosis sistémica.Se administraron fármacos antituberculosos y corticoides sistémicos, con buena respuesta clínica sistémica y ocular.El interferón beta 1b es un inmunomodulador apropiado para la esclerosis múltiple, pero sus principales efectos secundarios son alteraciones analíticas como leucopenia, linfocitopenia y trombocitopenia.Los linfocitos CD4+ T, leucocitos, macrófagos y granulocitos, con la producción de sus mediadores interferón gamma, IL-12 o TNF-α son fundamentales para controlar al Mycobacterium tuberculosis. Por ello, antes de introducir Interferón beta 1b, convendría realizar técnicas de screening, como la prueba de Mantoux o el interferon gamma release assay–(quantiferon-TB) para detectar posibles tuberculosis latentes potencialmente activables.AbstractAn ex-drug addict 50 years-old man came to our hospital with bilateral blurred vision. The anamnesis revealed his detoxification 20 years ago, with complete drug abstinence since then and a good social reinsertion. His medical history showed a serology for Hepatitis B+ and C+ viruses, but it showed VIH−. Recently, he began to suffer multiple sclerosis disease, but it was well-controlled with interferon-beta. He also mentioned to have suffered a recent, prolonged winter cold.The ophthalmologic examination enables identification of bilateral uveitis with keratic precipitates. The right eye funduscopy revealed several choroidal granulomas, besides healed and actives peripheral vasculitis zones. The left eye funduscopy was normal.After several diagnostic tests as chest x-ray and pulmonary CAT scan, several pulmonary nodules were found. Also, it was carried out a Mantoux-test that was strongly positive. The blood analysis showed neutropenia and lymphopenia. Consequently, we proposed a presumptive diagnosis of panuveitis related to systemic tuberculosis.Anti-tuberculosis drugs and systemic corticoids were given, with a good clinical and ocular response.Interferon-beta 1b is a suitable immunomodulator for multiple sclerosis treatment, but its main secondary effects are blood abnormalities as leukopenia, lymphocytopenia and thrombocytopenia.CD4+ T lymphocytes, leukocytes, macrophages and granulocytes, furthermore the production of its mediators: interferon gamma, IL-12 or TNF-α, are essential to control Mycobacterium tuberculosis. Thus, before introduction of interferon-beta 1b, it would be advisable to attempt screening techniques, as Mantoux-test or interferon gamma release assay (quantiferon-TB) to detect probably latent tuberculosis, potentially likely to be active again

Herbicidal potential of the natural compounds carvacrol, thymol, eugenol, p-cymene, citral and pelargonic acid in field conditions: indications for better performance

In recent years, interest in natural products with herbicidal activity as new tools for integrated weed management has increased. The European Union is demanding a reduction in the number of herbicides used, forbidding use of the most toxic ones, despite the problem of weed resistance increasing. Pelargonic acid (PA) is the only natural herbicide available in Spain. In this work, two field assays were performed with the natural compounds carvacrol (CAR), citral (CIT), eugenol (EUG), thymol (THY), p-cymene (P-CYM), (PA), and the combination of PA with CIT—all except P-CYM formulated by Seipasa—to test their herbicidal efficacy in real conditions. They were compared with commercial PA, glyphosate (GLY) and oxyfluorfen (OXY). In both experiments, GLY achieved the best weed control. Considering the natural herbicides, PA formulated by Seipasa and PA plus CIT were the most effective. From both experiments, some conclusions can be extracted for better herbicidal performance of natural products: (1) use products on sensitive weed species, (2) treat weeds at earlier phenological stages, (3) find the active doses in field conditions, (4) cover weeds well when treating, (5) ensure adequate formulation of products, and (6) develop a strategy for correct application.AGROSUS | Ref. 101084084Agencia Estatal de Investigación | Ref. RTI2018-094716-B-I0

The relationship between the levels of salivary cortisol and the presence of xerostomia in menopausal women : a preliminary study

Xerostomia is a particularly frequent occurrence among menopausal women, and is often associated with depression. Objectives: To evaluate the relationship between unstimulated salivary flow rate and the presence of xerostomia, and to determine the levels of salivary cortisol and its relationship with xerostomia. Study design: Thirty women were selected from patients attending the Department of Medicine and Buccofacial surgery, and formed into two groups, study and control. Samples of unstimulated salivary flow were collected, and the amounts of salivary cortisol determined using the ELISA technique (enzyme-linked immunosorbent assay). Results: The mean unstimulated salivary flow rates for the control and study group were 0.37 ± 0.28 ml/min and 0.24 ± 0.18 ml/min, respectively. The concentration of salivary cortisol was 3.47 ± 1.64 ng/ml for the control group and 2.29 ± 2.60 ng/ml for the study group. The statistical tests applied showed no significant differences for either variable between the two groups in the study. Conclusions: The results of the present study indicate that there is no relationship between variations in the rates of unstimulated salivary flow and the corresponding concentration of cortisol

New Geological Evidence of the 1755 Lisbon Tsunami from the Rock of Gibraltar (Southern Iberian Peninsula)

This paper presents the easternmost mineralogical and geochemical evidence of the 1755 Lisbon tsunami found in the Western Mediterranean. This multidisciplinary analysis of a sediment core obtained in Gibraltar (southern Iberian Peninsula) has allowed us to differentiate a tsunamiite from an old lagoon (The Inundation). This tsunamigenic layer has increased levels of calcite and aragonite and higher concentrations of Ba and ferromagnesian elements in comparison with the underlying lagoonal sediments of this core. This layer is also differentiated by its paleontological record, with the introduction of marine species within this lagoon. The uppermost part of the core includes a transition from swampy/marsh paleoenvironments to terrestrial scenarios, with a final anthropogenic filling occurring during the last century

Preparación de bioles orgánicos

Los biofertilizantes provienen de animales, restos vegetales, alimentos y otras fuentes orgánicas naturales, los bioles se están usando para sustituir a los fertilizantes químicos que son los que están dañando el medio ambiente. Con el uso de fertilizantes orgánicos estamos cuidando en medio ambiente, sin dañar nuestros suelos y sobre todo no contaminando los mantos acuíferos, de igual manera se está cuidando la salud humana ya que se producen alimentos libres de químicos. Con este manual estamos enseñando paso a paso como producir nuestros biofertilizantes con el fin de reducir o evitar el uso de fertilizantes químicos