Simvastatin Enhances the Effects of Radiotherapy and Cetuximab on a Cell Line (FaDu) Derived from a Squamous Cell Carcinoma of Head and Neck

Radiotherapy (XRT) delivered with the antibody cetuximab is a standard treatment option for squamous cell carcinomas of head and neck (SCCNH). Cetuximab acts by blocking epidermal growth factor receptor (EGFR) signaling to inhibit cancer progression. However, a significant percentage of patients will not respond to XRT and cetuximab. Statins reduce the synthesis of cholesterol and isoprenoid derivates that may be required for efficient EGFR signaling. We assessed whether the statin simvastatin could improve this combined therapy. In vitro, simvastatin enhanced the effects of XRT alone and in combination with cetuximab in wound healing, cell proliferation, and clonogenic assays in FaDu cells. These results were reflected in xenoimplanted tumors growing into subcutaneous tissue of athymic mice where concomitant treatment with simvastatin decreased tumor growth. Consistently, lower levels of phosphorylated extracellular signal-regulated kinases 1 and 2, phosphatidylinositol 3-kinase/AKT-protein kinase B, and signal transducer and activator of transcription 3 oncoproteins and higher levels of caspase-3 and apoptosis in cell cultures and xenografts were observed. The EGFR-overexpressing A431 cell line was used to reproduce these antitumor effects of simvastatin. Our findings suggest that simvastatin may improve the efficiency of concomitant XRT and cetuximab. Further investigation in the treatment of SCCNH is warranted

Dones mares i treballadores : anàlisi dels usos del temps i les estratègies de conciliació

La incorporació de la dona al món laboral planteja una problemática social associada, doncs l'aparició de la dona en l'espai públic no ha supòs una renuncia a l'espai domèstic, convertint-se com a conseqüència en una doble jornada. Aquest treball d'investigació ens serà una eina útil per a conèixer les conseqüències d'aquest fenomen i mesurar el grau en que aquesta doble jornada afecta a la qualitat de vida de les dones

Reasons for deciding to die in hospital or at home. The vision of professionals

Objetivo: Conocer las razones que llevan a decidir que los pacientes terminales mueran en el hospital o en su domicilio, desde la perspectiva de los/las profesionales. Método: Estudio cualitativo fenomenológico. Muestreo intencionado. Se realizaron cuatro grupos focales multidisciplinarios: dos en hospitales y dos en centros de Atención Primaria de Salud (APS) de Sevilla.Participaron 29 profesionales con al menos 2 años de experiencia con pacientes terminales, siguiendo el criterio de saturación teórica. Resultados: Las respuestas obtenidas del guion inicial se agruparon en tres categorías centrales: paciente y familia, profesionales y proceso asistencial. No suele consultarse al paciente sobre sus preferencias respecto al lugar donde quiere morir, y si además la familia las desconoce, no se puede realizar una planificación anticipada de cuidados. La familia elige el hospital por inseguridad respecto a la posibilidad de seguimiento y recursos en APS. Los/las profesionales poseen formación para abordar la muerte, pero no se sienten preparados, focalizando la atención en aspectos clínicos o administrativos. El proceso asistencial favorece a los pacientes oncológicos, pues es más sencillo identificar su terminalidad. No hay equidad en los recursos y es mejorable la comunicación interniveles. No se facilita la integración de la familia en el proceso que interfiere en su toma de decisiones. Conclusiones: Se debe fomentar la planificación anticipada de cuidados y usar el documento de voluntades anticipadas, la comunicación y la coordinación interniveles, dotar de recursos, especialmente a APS, y formar y preparar a los/las profesionales para abordar la muerte. Hay que implicar a la familia en el proceso, aportándole el apoyo necesario

Characterization of lignin and lignin-derivatives from biomass. Application as expander of lead-acid battery

Expanders, as lignosulfonates, are crucial for a good performance of Pb/acid batteries. In the process of discharge, the Pb and the PbO2 go to PbSO4. The formed PbSO4 is adsorbed on the surface of the Pb electrode and dramatically reduces the lifetime of the battery by the formation of big PbSO4 crystals. In order to prevent that, the addition of expanders in the negative electrode is an economic solution to prevent the formation of big crystals. In this investigation, we propose the synthesis of several lignosulfonates obtained from lignin of many biomass origins. We have derivatized nine samples of lignin via microwave-assisted sulfonation, then we have characterized how efficient is the chosen synthesis method. The lignosulfonates obtained have been characterized by infrared spectroscopy (IR), proton nuclear magnetic resonance (1HNMR), two-dimensional correlated spectroscopy (COSY), and elemental analysis to acquire some relevant information about their structure in terms of functional groups. In this way, three commercial lignosulfonates, Vanisperse A, Indulin AT, and Oakwood, have been selected as references for our comparisons. Moreover, we have checked their electrochemical properties, using electrochemical techniques to compare their behavior with respect to the commercial lignosulfonates. Finally, we have selected one of them and we have tested its performance as an expander in a Pb/acid battery. That result is a very promising first approach, and we can conclude that lignosulfonates derivatives are a good and low-cost choice to improve the lifetime of Pb/acid batteries. In particular, it is shown that the incorporation of LignosB improves the cell formation as well as the first capacity (36.30% more) and the charge acceptance (63.16% more), being these relevant parameters in the performance of Pb/acid batterie

The use of caspase inhibitors in pulsed-field gel electrophoresis may improve the estimation of radiation-induced DNA repair and apoptosis

Background: Radiation-induced DNA double-strand break (DSB) repair can be tested by using pulsed-field gel electrophoresis (PFGE) in agarose-encapsulated cells. However, previous studies have reported that this assay is impaired by the spontaneous DNA breakage in this medium. We investigated the mechanisms of this fragmentation with the principal aim of eliminating it in order to improve the estimation of radiation-induced DNA repair. Methods: Samples from cancer cell cultures or xenografted tumours were encapsulated in agarose plugs. The cell plugs were then irradiated, incubated to allow them to repair, and evaluated by PFGE, caspase-3, and histone H2AX activation (gamma H2AX). In addition, apoptosis inhibition was evaluated through chemical caspase inhibitors. Results: We confirmed that spontaneous DNA fragmentation was associated with the process of encapsulation, regardless of whether cells were irradiated or not. This DNA fragmentation was also correlated to apoptosis activation in a fraction of the cells encapsulated in agarose, while non-apoptotic cell fraction could rejoin DNA fragments as was measured by gamma H2AX decrease and PFGE data. We were able to eliminate interference of apoptosis by applying specific caspase inhibitors, and improve the estimation of DNA repair, and apoptosis itself. Conclusions: The estimation of radiation-induced DNA repair by PFGE may be improved by the use of apoptosis inhibitors. The ability to simultaneously determine DNA repair and apoptosis, which are involved in cell fate, provides new insights for using the PFGE methodology as functional assay

Fractionation of Lignocellulosic Biomass by Selective Precipitation from Ionic Liquid Dissolution

We propose the treatment of barley straw with 1-ethyl-3-methylimidazolium acetate [EMIMAcO] ionic liquids (ILs) and subsequent precipitation with antisolvent mixtures, thus allowing the separation of the sugar-rich fractions (cellulose and hemicellulose) from the lignin fraction. For this purpose, different concentration ranges of acetone:water antisolvent mixtures were studied. In all cases, a high recovery percentage and a high and effective separation of fractions was achieved for 1:1 acetone:water. The fractionated lignocellulosic compounds were studied by using infrared spectroscopy, scanning electron microscopy and 1H nuclear magnetic resonance characterization techniques. This method allows the possibility of reusing IL, confirming the versatility of the established method. The fraction rich in cellulose and hemicellulose was subjected to acid hydrolysis (0.2 mol/L H2SO4) for 5 h at 140 °C, obtaining a yield of total reducing sugars of approximately 80%, much higher than those obtained in non-pretreated samples.This research was funded by Comunidad de Madrid (Spain) and ERDF (European Regional Development Fund), grant numbers S2013/MAE-2882 (RESTOENE-2-CM), S2018/EMT-4344 (BIOTRES-CM) and CSIC (201880E029). M.L.-S. acknowledges the support of the European Social Fund and Community of Madrid for her contracPeer reviewe

Comparison of First-Pass Effect in Aspiration vs. Stent-Retriever for Acute Intracranial ICA Occlusion

The purpose of this study is to evaluate the best endovascular approach (aspiration or stent-retriever) and the impact of stent retriever size and length on clinical and angiographic outcomes in patients with acute intracranial ICA occlusion. We conducted a retrospective analysis of a prospective database of consecutive patients with acute intracranial ICA occlusion undergoing endovascular treatment in four Comprehensive Stroke Center between June-2019 and December-2020. We include 121 patients; Stent-retriever (SR) was used as first technical approach in 107 patients (88.4%) and aspiration was used in 14 patients (11.6%). SR group had higher rate of FPE compared to aspiration group (29 vs. 0%, p = 0.02). In SR subgroup, treatment highlighted higher FPE in the 6 x 50 SR (37.7%), than in the rest of the SR which are 21.2% (4-5 mm size and 20-50 mm length SR) and 19% (6 mm size and 25-40 mm length SR), but it was not found to be statistically significant. There were no other significant differences across the groups regarding primary angiographic or clinical outcomes. In our intracranial ICA occlusion series, stent retrievers were superior to direct aspiration in obtaining FPEs and mFPEs, and longer devices achieved better results with no statistically significant difference. Further studies evaluating the effects of different ICA clot removal approaches are warranted to confirm these results

Resource Recovery Potential From Lignocellulosic Feedstock Upon Lysis With Ionic Liquids

Lignocellulosic residues from energy crops offer a high potential to recover bioproducts and biofuels that can be used as raw matter for agriculture activities within a circular economy framework. Anaerobic digestion (AD) is a well-established driver to convert these residues into energy and bioproducts. However, AD of lignocellulosic matter is slow and yields low methane potential, and therefore several pre-treatment methods have been proposed to increase the energy yield of this process. Hereby, we have assessed the pre-treatment of lignocellulosic biomass (barley straw) with the ionic liquid (IL) 1-ethyl-3-methylimidazolium acetate and its effect on the biochemical methane potential (BMP). The BMP of the residue was evaluated at different inoculum to substrate (I/S) ratios and working under meso and thermophilic conditions. Solids destruction upon AD is highly enhanced by the IL-pretreatment. This also resulted in a higher BMP, both in mesophilic as well as thermophilic conditions. At the optimum I/S ratio of 2:1 (dried weight, dw), the BMP of the IL-pre-treated feedstock increased 28 and 80% for 35 days of thermophilic and mesophilic AD, respectively, as compared to the fresh feedstock, achieving values of 364 and 412 LCH4/kgTS. We also explored the effect of this pretreatment on the phosphorus recovery potential from the digestate upon release from the AD process. Thermophilic anaerobic digestion of IL-pre-treated biomass provided the highest P recovery potential from lignocellulosic residues (close to 100% of the theoretical P content of the lignocellulosic feedstock). Therefore, the pretreatment of lignocellulosic feedstock with IL before AD is a promising platform to obtain bioenergy and recover P to be regained for the agriculture sector

Search for Specific Biomarkers of IFNβ Bioactivity in Patients with Multiple Sclerosis

Myxovirus A (MxA), a protein encoded by the MX1 gene with antiviral activity, has proven to be a sensitive measure of IFNβ bioactivity in multiple sclerosis (MS). However, the use of MxA as a biomarker of IFNβ bioactivity has been criticized for the lack of evidence of its role on disease pathogenesis and the clinical response to IFNβ. Here, we aimed to identify specific biomarkers of IFNβ bioactivity in order to compare their gene expression induction by type I IFNs with the MxA, and to investigate their potential role in MS pathogenesis. Gene expression microarrays were performed in PBMC from MS patients who developed neutralizing antibodies (NAB) to IFNβ at 12 and/or 24 months of treatment and patients who remained NAB negative. Nine genes followed patterns in gene expression over time similar to the MX1, which was considered the gold standard gene, and were selected for further experiments: IFI6, IFI27, IFI44L, IFIT1, HERC5, LY6E, RSAD2, SIGLEC1, and USP18. In vitro experiments in PBMC from healthy controls revealed specific induction of selected biomarkers by IFNβ but not IFNγ, and several markers, in particular USP18 and HERC5, were shown to be significantly induced at lower IFNβ concentrations and more selective than the MX1 as biomarkers of IFNβ bioactivity. In addition, USP18 expression was deficient in MS patients compared with healthy controls (p = 0.0004). We propose specific biomarkers that may be considered in addition to the MxA to evaluate IFNβ bioactivity, and to further explore their implication in MS pathogenesis