Analysis of Polymorphisms of the Vitamin D Receptor, Estrogen Receptor, and Collagen Iα1 Genes and Their Relationship With Height in Children With Bone Cancer

The authors' objectives were to compare height at diagnosis of children with bone tumors with that of Spanish reference children; to analyze the frequency of the genotypes for the polymorphisms of the vitamin D receptor (VDR), estrogen receptor (ER), and collagen Ialpha1 (COLIalpha1) genes in patients and in healthy controls; and to test the relationship between the genetic markers and height. PATIENTS AND METHODS: Height and weight at diagnosis were measured in 58 osteosarcoma and 36 Ewing sarcoma patients and compared with standards published for Spanish reference children according to sex and age. For the molecular analysis, genetic polymorphisms of the VDR (Fok I, Apa I, and TaqI), ER (Pvu II and XbaI), and COLIalpha1 (Msc I) genes were characterized in 72 osteosarcoma and 53 Ewing sarcomas and in a group of 143 healthy matched children. RESULTS: Osteosarcoma and Ewing sarcoma patients were significantly taller than Spanish reference children. Osteosarcoma patients showed a significantly higher frequency of the Ff genotype for the Fok I polymorphism (VDR gene) than the control group. The odds ratio for this genotype was 1.78, with an increased relative risk of 78% for heterozygous Ff carriers. Among Ewing sarcoma patients, this same genotype was significantly associated with lower height than homozygotes (FF or ff). CONCLUSIONS: Children with bone cancer are significantly taller than the reference population, which may be influenced by the genotype for the Fok I polymorphism of the VDR gene

Screening of the human tumor necrosis factor-alpha (TNF-α) gene promoter polymorphisms by PCR–DGGE analysis

We have designed a new PCR-DGGE technique that enables detection of base changes in the TNF-alpha gene promoter. Screening of 130 samples from Spanish children has shown that this technique accurately detects the altered band patterns induced by the presence of the polymorphisms at positions -376, -308, -238 and -163 of the promoter sequence. Although further analysis are needed to fully characterise the alterations detected, we believe that this PCR-DGGE technique is a rapid and sensitive first approach to the genetic characterisation of the TNF-alpha promote

Cambio Climático en el Mediterráneo Español

Semi-enclosed and bounded by three continents, the Mediterranean sea is a region highly vulnerable to human activities, i.e.: the population surge along the coasts, the tourism pressure, the maritime traffic, the agriculture and the fishery exploitation, all have a potential impact on the Mediterranean environment. In addition, effective initiatives against the Global Climate Change need to be attempted in order to preserve our marine environment and to achieve a sustainable development of its resources. Prevention and adaptation to this new threat must be based on the rigorous and scientific knowledge accomplished through the systematic and continuous observation of the sea, and through the collection of multidisciplinary time-series and the subsequent analysis. This report responds to this necessity. The main goals of the Instituto Español de Oceanografía (IEO) are to generate scientific knowledge, as well as to assess and to inform the public about the state of the sea. The IEO is primary focussed on the study of the variety of phenomena influencing spanish coasts, including the process of Climate Change. To meet these objectives, a large set of actions have been planned. Some of them are already being implemented, such as a multidisciplinary observation system in the shelf and continental slope waters, or periodic scientific reports dealing with the detection and quantification of Climate Change effects and of other possible environmental impacts. The present report is the first of a series of future contributions. Besides the IEO, other Spanish institutions such as the ICM (CSIC), Puertos del Estado (PE), the IMEDEA (CSIC), the UMA, the UIB and the INM, involved in the monitoring, analysis and modelling of the Mediterranean sea, have also participated in it. The results show clear evidences of the effect of Climate Change in the physical properties of the mediterranean waters since 1948; in particular, the temperature and salinity increase of the deep waters, the accelerated rise of sea level since the early 1990s, and the air and sea surface temperature increase during the second half of the XX century.Versión del edito

Copernicus Ocean State Report, issue 6

The 6th issue of the Copernicus OSR incorporates a large range of topics for the blue, white and green ocean for all European regional seas, and the global ocean over 1993–2020 with a special focus on 2020

Minimal information for studies of extracellular vesicles 2018 (MISEV2018):a position statement of the International Society for Extracellular Vesicles and update of the MISEV2014 guidelines

The last decade has seen a sharp increase in the number of scientific publications describing physiological and pathological functions of extracellular vesicles (EVs), a collective term covering various subtypes of cell-released, membranous structures, called exosomes, microvesicles, microparticles, ectosomes, oncosomes, apoptotic bodies, and many other names. However, specific issues arise when working with these entities, whose size and amount often make them difficult to obtain as relatively pure preparations, and to characterize properly. The International Society for Extracellular Vesicles (ISEV) proposed Minimal Information for Studies of Extracellular Vesicles (“MISEV”) guidelines for the field in 2014. We now update these “MISEV2014” guidelines based on evolution of the collective knowledge in the last four years. An important point to consider is that ascribing a specific function to EVs in general, or to subtypes of EVs, requires reporting of specific information beyond mere description of function in a crude, potentially contaminated, and heterogeneous preparation. For example, claims that exosomes are endowed with exquisite and specific activities remain difficult to support experimentally, given our still limited knowledge of their specific molecular machineries of biogenesis and release, as compared with other biophysically similar EVs. The MISEV2018 guidelines include tables and outlines of suggested protocols and steps to follow to document specific EV-associated functional activities. Finally, a checklist is provided with summaries of key points

Hyperoxemia and excess oxygen use in early acute respiratory distress syndrome : Insights from the LUNG SAFE study

Publisher Copyright: © 2020 The Author(s). Copyright: Copyright 2020 Elsevier B.V., All rights reserved.Background: Concerns exist regarding the prevalence and impact of unnecessary oxygen use in patients with acute respiratory distress syndrome (ARDS). We examined this issue in patients with ARDS enrolled in the Large observational study to UNderstand the Global impact of Severe Acute respiratory FailurE (LUNG SAFE) study. Methods: In this secondary analysis of the LUNG SAFE study, we wished to determine the prevalence and the outcomes associated with hyperoxemia on day 1, sustained hyperoxemia, and excessive oxygen use in patients with early ARDS. Patients who fulfilled criteria of ARDS on day 1 and day 2 of acute hypoxemic respiratory failure were categorized based on the presence of hyperoxemia (PaO2 > 100 mmHg) on day 1, sustained (i.e., present on day 1 and day 2) hyperoxemia, or excessive oxygen use (FIO2 ≥ 0.60 during hyperoxemia). Results: Of 2005 patients that met the inclusion criteria, 131 (6.5%) were hypoxemic (PaO2 < 55 mmHg), 607 (30%) had hyperoxemia on day 1, and 250 (12%) had sustained hyperoxemia. Excess FIO2 use occurred in 400 (66%) out of 607 patients with hyperoxemia. Excess FIO2 use decreased from day 1 to day 2 of ARDS, with most hyperoxemic patients on day 2 receiving relatively low FIO2. Multivariate analyses found no independent relationship between day 1 hyperoxemia, sustained hyperoxemia, or excess FIO2 use and adverse clinical outcomes. Mortality was 42% in patients with excess FIO2 use, compared to 39% in a propensity-matched sample of normoxemic (PaO2 55-100 mmHg) patients (P = 0.47). Conclusions: Hyperoxemia and excess oxygen use are both prevalent in early ARDS but are most often non-sustained. No relationship was found between hyperoxemia or excessive oxygen use and patient outcome in this cohort. Trial registration: LUNG-SAFE is registered with ClinicalTrials.gov, NCT02010073publishersversionPeer reviewe

Telomerase activity and telomere length in primary and metastatic tumors from pediatric bone cancer patients

The presence of telomerase activity has been analyzed in almost all tumor types and tumor-derived cell lines. However, there are very few studies that focus on the presence of telomerase activity in bone tumors, and most of them report analysis on very few samples or bone-derived cell lines. The objective of this study was to analyze the telomere length and telomerase activity in primary tumors and metastatic lesions from pediatric osteosarcoma and Ewing's sarcoma patients. The presence of telomerase activity was analyzed by the telomeric repeat amplification protocol assay, and the telomere length was measured by Southern blot. Results were related to survival and clinical outcome. Telomerase activity was detected in 85% of the bone tumor metastases (100% Ewing's sarcomas and 75% osteosarcomas) but only in 12% of the primary tumors (11.1% osteosarcomas and 12.5% Ewing's sarcomas). Bone tumor tissues with telomerase activity had mean telomere lengths 3 kb shorter than those with no detectable telomerase activity (p = 0.041). The presence of telomerase activity was associated with survival (p = 0.009), and longer event-free survival periods were found in patients who lacked telomerase activity compared with those who had detectable telomerase activity levels in their tumor tissues (p = 0.037). The presence of longer telomeres in primary pediatric bone tumors than in metastases could be indicative of alternative mechanisms of lengthening of telomeres for their telomere maintenance rather than telomerase activity. Nevertheless, the activation of telomerase seems to be a crucial step in the malignant progression and acquisition of invasive capability of bone tumors

Análisis de la implicación de los genes de supresión tumoral TP53, p16INK4, p21WAF1, RB1 y de las enzimas metabolizadoras de drogas en el desarrollo de tumores óseos en niños

Several tumor suppressor genes such as p16INK4, TP53, RB1 y p21WAF1 are involved in cell cycle regulation in response to DNA damage and belong to the complex pathway that regulates cell proliferation and/or differentiation. We have investigated the presence of mutations in those genes and polymorphisms of Drug Metabolizing Enzymes that could be involved in the development of pediatric bone tumors or in their outcome. MATERIALS AND METHODS: By means of PCR-based techniques, we have analyzed the presence of variations in the coding sequence of p16INK4, TP53, RB1 y p21WAF1 and of the Drug Metabolizing Enzymes in a group of 82 osteosarcomas and 47 Ewing's sarcomas as well as in a control group of 115 healthy children. RESULTS: We detected mutations of the TP53 gene in about 25% of the samples analyzed, most frequently in association with tumors of poor prognosis or reduced survival. The p16INK4 gene was homozygously deleted in 18% of the osteosarcomas, also associated with poor prognosis and unfavourable histologic subtypes; RB1 was altered in 21% of the osteosarcomas. We did not detect relevant associations between polymorphisms of the Drug Metabolizing Enzymes or mutation of the p21WAF1 and development of pediatric bone tumors. CONCLUSIONS: Alteration of TP53, p16INK4 and p21WAF1 seems to be involved in the development of pediat

Direct long-read RNA sequencing identifies a subset of questionable exitrons likely arising from reverse transcription artifacts

Resistance to CD19-directed immunotherapies in lymphoblastic leukemia has been attributed, among other factors, to several aberrant CD19 pre-mRNA splicing events, including recently reported excision of a cryptic intron embedded within CD19 exon 2. While “exitrons” are known to exist in hundreds of human transcripts, we discovered, using reporter assays and direct long-read RNA sequencing (dRNA-seq), that the CD19 exitron is an artifact of reverse transcription. Extending our analysis to publicly available datasets, we identified dozens of questionable exitrons, dubbed “falsitrons,” that appear only in cDNA-seq, but never in dRNA-seq. Our results highlight the importance of dRNA-seq for transcript isoform validation

Cambio climático en el Mediterráneo español. Segunda edición actualizada

The first edition of the report “Climate Change in the Spanish Mediterranean” acknowledged the necessity of monitoring environmental conditions within the Mediterranean Sea and it stated that initiatives aimed at preserving and achieving a sustainable development of its resources should be based on a rigorous and scientific knowledge. The first edition of this report attempted to establish the basis for future works and detected and quantified the sea level rise of waters surrounding the Mediterranean Spanish coasts, the temperature and salinity increase of deep waters, and the warming of the air and sea surface waters. The study of these and other man-made threats on the marine environment is an open question and requires a continuous monitoring effort. Thanks to the collaboration with other Spanish institutions such as ICM (CSIC), Puertos del Estado (PE), IMEDEA (CSIC), UMA, UIB and AEMET, as well as the own monitoring programs from the Instituto Español de Oceanografía (RADMED program), this second edition continues the previous report, analyzing time series extended to July 2008 and evidencing the persistence of the above mentioned warming trends in the Spanish Mediterranean. This and future updated reports, the activities of the IEO Mediterranean Group on Climate Change, and the collaboration with the already mentioned institutions intend to be a tool for the continuous surveillance of the Mediterranean Spanish waters and the assessment for its sustainable exploitation.Versión del edito