An approach to corporate volunteering in Spain

This study aims to analyse the role of corporate volunteerism in the framework of corporate social responsibility of enterprises. After reviewing the active components in the employee volunteering concept, we present the steps taken at the European level in this area, focusing on Spain’s situation. We start with a search and comparison of information on the topic published by the major Spanish listed companies. This first approach verifies that the data are disclosed from various sources and presented heterogeneously. Then, we identify the sector that concentrates a more significant number of employees in volunteer activities. Subsequently, we focus on this sector to explore the type of volunteer activities these companies reveal according to Spanish legislation. The study sheds light on corporate governance practices, especially the disclosure of information about this activity type

Cell Cycle Deregulation in Ewing's Sarcoma Pathogenesis

Ewing's sarcoma is a highly aggressive pediatric tumor of bone that usually contains the characteristic chromosomal translocation t(11;22)(q24;q12). This translocation encodes the oncogenic fusion protein EWS/FLI, which acts as an aberrant transcription factor to deregulate target genes necessary for oncogenesis. One key feature of oncogenic transformation is dysregulation of cell cycle control. It is therefore likely that EWS/FLI and other cooperating mutations in Ewing's sarcoma modulate the cell cycle to facilitate tumorigenesis. This paper will summarize current published data associated with deregulation of the cell cycle in Ewing's sarcoma and highlight important questions that remain to be answered

Increased risk for other cancers in individuals with Ewing sarcoma and their relatives.

BackgroundThere are few reports of the association of other cancers with Ewing sarcoma in patients and their relatives. We use a resource combining statewide genealogy and cancer reporting to provide unbiased risks.MethodsUsing a combined genealogy of 2.3 million Utah individuals and the Utah Cancer Registry (UCR), relative risks (RRs) for cancers of other sites were estimated in 143 Ewing sarcoma patients using a Cox proportional hazards model with matched controls; however, risks in relatives were estimated using internal cohort-specific cancer rates in first-, second-, and third-degree relatives.ResultsCancers of three sites (breast, brain, complex genotype/karyotype sarcoma) were observed in excess in Ewing sarcoma patients. No Ewing sarcoma patients were identified among first-, second-, or third-degree relatives of Ewing sarcoma patients. Significantly increased risk for brain, lung/bronchus, female genital, and prostate cancer was observed in first-degree relatives. Significantly increased risks were observed in second-degree relatives for breast cancer, nonmelanoma eye cancer, malignant peripheral nerve sheath cancer, non-Hodgkin lymphoma, and translocation sarcomas. Significantly increased risks for stomach cancer, prostate cancer, and acute lymphocytic leukemia were observed in third-degree relatives.ConclusionsThis analysis of risk for cancer among Ewing sarcoma patients and their relatives indicates evidence for some increased cancer predisposition in this population which can be used to individualize consideration of potential treatment of patients and screening of patients and relatives

C/EBPβ-1 promotes transformation and chemoresistance in Ewing sarcoma cells.

CEBPB copy number gain in Ewing sarcoma was previously shown to be associated with worse clinical outcome compared to tumors with normal CEBPB copy number, although the mechanism was not characterized. We employed gene knockdown and rescue assays to explore the consequences of altered CEBPB gene expression in Ewing sarcoma cell lines. Knockdown of EWS-FLI1 expression led to a decrease in expression of all three C/EBPβ isoforms while re-expression of EWS-FLI1 rescued C/EBPβ expression. Overexpression of C/EBPβ-1, the largest of the three C/EBPβ isoforms, led to a significant increase in colony formation when cells were grown in soft agar compared to empty vector transduced cells. In addition, depletion of C/EBPβ decreased colony formation, and re-expression of either C/EBPβ-1 or C/EBPβ-2 rescued the phenotype. We identified the cancer stem cell marker ALDH1A1 as a target of C/EBPβ in Ewing sarcoma. Furthermore, increased expression of C/EBPβ led to resistance to chemotherapeutic agents. In summary, we have identified CEBPB as an oncogene in Ewing sarcoma. Overexpression of C/EBPβ-1 increases transformation, upregulates expression of the cancer stem cell marker ALDH1A1, and leads to chemoresistance

Immunolocalization of NLRP3 Inflammasome in Normal Murine Airway Epithelium and Changes following Induction of Ovalbumin-Induced Airway Inflammation

Little is known about innate immunity and components of inflammasomes in airway epithelium. This study evaluated immunohistological evidence for NLRP3 inflammasomes in normal and inflamed murine (Balb/c) airway epithelium in a model of ovalbumin (OVA) induced allergic airway inflammation. The airway epithelium of control mice exhibited strong cytoplasmic staining for total caspase-1, ASC, and NLRP3, whereas the OVA mice exhibited strong staining for active caspase-1, with redistribution of caspase-1, IL-1β and IL-18, indicating possible activation of the NLRP3 inflammasome. Active caspase-1, NLRP3, and other inflammasome components were also detected in tissue eosinophils from OVA mice, and may potentially contribute to IL-1β and IL-18 production. In whole lung, inRNA expression of NAIP and procaspase-1 was increased in OVA mice, whereas NLRP3, IL-1β and IL-18 decreased. Some OVA-treated mice also had significantly elevated and tightly correlated serum levels of IL-1β and TNFα. In cultured normal human bronchial epithelial cells, LPS priming resulted in a significant increase in NLRP3 and II-lp protein expression. This study is the first to demonstrate NLRP3 inflammasome components in normal airway epithelium and changes with inflammation. We propose activation and/or luminal release of the inflammasome is a feature of allergic airway inflammation which may contribute to disease pathogenesis

Clinical and biochemical function of polymorphic NR0B1 GGAA-microsatellites in Ewing sarcoma: a report from the Children\u27s Oncology Group.

BACKGROUND: The genetics involved in Ewing sarcoma susceptibility and prognosis are poorly understood. EWS/FLI and related EWS/ETS chimeras upregulate numerous gene targets via promoter-based GGAA-microsatellite response elements. These microsatellites are highly polymorphic in humans, and preliminary evidence suggests EWS/FLI-mediated gene expression is highly dependent on the number of GGAA motifs within the microsatellite. OBJECTIVES: Here we sought to examine the polymorphic spectrum of a GGAA-microsatellite within the NR0B1 promoter (a critical EWS/FLI target) in primary Ewing sarcoma tumors, and characterize how this polymorphism influences gene expression and clinical outcomes. RESULTS: A complex, bimodal pattern of EWS/FLI-mediated gene expression was observed across a wide range of GGAA motifs, with maximal expression observed in constructs containing 20-26 GGAA motifs. Relative to white European and African controls, the NR0B1 GGAA-microsatellite in tumor cells demonstrated a strong bias for haplotypes containing 21-25 GGAA motifs suggesting a relationship between microsatellite function and disease susceptibility. This selection bias was not a product of microsatellite instability in tumor samples, nor was there a correlation between NR0B1 GGAA-microsatellite polymorphisms and survival outcomes. CONCLUSIONS: These data suggest that GGAA-microsatellite polymorphisms observed in human populations modulate EWS/FLI-mediated gene expression and may influence disease susceptibility in Ewing sarcoma

Enantiomeric profiling of chiral illicit drugs in a pan-European study

The aim of this paper is to present the first study on spatial and temporal variation in the enantiomeric profile of chiral drugs in eight European cities. Wastewater-based epidemiology (WBE) and enantioselective analysis were combined to evaluate trends in illicit drug use in the context of their consumption vs direct disposal as well as their synthetic production routes. Spatial variations in amphetamine loads were observed with higher use in Northern European cities. Enantioselective analysis showed a general enrichment of amphetamine with the R-(−)-enantiomer in wastewater indicating its abuse. High loads of racemic methamphetamine were detected in Oslo (EF = 0.49 ± 0.02). This is in contrast to other European cities where S-(+)-methamphetamine was the predominant enantiomer. This indicates different methods of methamphetamine synthesis and/or trafficking routes in Oslo, compared with the other cities tested. An enrichment of MDMA with the R-(−)-enantiomer was observed in European wastewaters indicating MDMA consumption rather than disposal of unused drug. MDA's chiral signature indicated its enrichment with the S-(+)-enantiomer, which confirms its origin from MDMA metabolism in humans. HMMA was also detected at quantifiable concentrations in wastewater and was found to be a suitable biomarker for MDMA consumption. Mephedrone was only detected in wastewater from the United Kingdom with population-normalised loads up to 47.7 mg 1000 people−1 day−1. The enrichment of mephedrone in the R-(+)-enantiomer in wastewater suggests stereoselective metabolism in humans, hence consumption, rather than direct disposal of the drug. The investigation of drug precursors, such as ephedrine, showed that their presence was reasonably ascribed to their medical use