Gold-catalyzed direct cycloketalization of acetonide-tethered alkynes in the presence of water

A methodology for the direct preparation of bridged acetals from acetonide-tethered alkynes under gold catalysis in the presence of water has been developed. The bicyclic ring structures bearing a bridged five-membered ring arise from the regioselective bis-oxycyclization by initial attack of the oxygen atom to the internal alkyne carbon. © 2012 Elsevier Ltd. All rights reserved.Peer Reviewe

La influencia de losfactores docentes en la creatividad del alumnado

En el presente trabajo, se pretende llevar a cabo una investigación para comprobar la influencia de la metodología docente, sobre la creatividad del alumnado. En cuanto a la metodología, encontramos un repaso teórico sobre la creatividad, su relación con la inteligencia, los elementos que la fomentan, las fases del proceso creativo y la importancia en el aula. Se realiza una investigación de campo con una muestra de dos clases de 20 alumnos1 y sus respectivos docentes, cada una perteneciente a un centro educativo. A los docentes se les analizará a través de un cuestionario tipo Likert y unas preguntas. Por otro lado, los alumnos realizarán un test de la creatividad de Torrance, que constará de tres partes, para evaluar distintos aspectos creativos. El objetivo de este estudio es clasificar la metodología de los docentes estudiados, como tradicional o innovadora, para compararlo, con los resultados que obtenga el alumnado de sus respectivas clases, en los test de la creatividad, comprobando así, si su metodología influye de manera directa en el nivel de creatividad de los niños de su aula.This final project is intended to investigate to verify the influence of the teaching methodology on the creativity of the students. Regarding the methodology, we find a theoretical review on creativity, its relationship with intelligence, the elements that promote it, the phases of the creative process, and its importance in the classroom. A field investigation is carried out with a sample of two classes of 20 students and their respective teachers, each one belonging to an educational center. Teachers will be analyzed through a Likert-type questionnaire and some questions. On the other hand, to analyzed students, they are going to realize a Torrance creativity test, which will consist of three parts, to evaluate different creative aspects. The objective of this study is to classify the studied teacher’s methodology, to classify it as traditional or innovative, to compare it, with the results obtained by the students of their respective classes, in the creativity tests. In that way, we check how their teaching methodologies influence directly the creativity level of the children from their classroom.Universidad de Sevilla. Grado en Educación Primari

The Structure of a Biologically Active Influenza Virus Ribonucleoprotein Complex

The influenza viruses contain a segmented, single-stranded RNA genome of negative polarity. Each RNA segment is encapsidated by the nucleoprotein and the polymerase complex into ribonucleoprotein particles (RNPs), which are responsible for virus transcription and replication. Despite their importance, information about the structure of these RNPs is scarce. We have determined the three-dimensional structure of a biologically active recombinant RNP by cryo-electron microscopy. The structure shows a nonameric nucleoprotein ring (at 12 Å resolution) with two monomers connected to the polymerase complex (at 18 Å resolution). Docking the atomic structures of the nucleoprotein and polymerase domains, as well as mutational analyses, has allowed us to define the interactions between the functional elements of the RNP and to propose the location of the viral RNA. Our results provide the first model for a functional negative-stranded RNA virus ribonucleoprotein complex. The structure reported here will serve as a framework to generate a quasi-atomic model of the molecular machine responsible for viral RNA synthesis and to test new models for virus RNA replication and transcription

Associations of accumulated persistent organic pollutants in breast adipose tissue with the evolution of breast cancer after surgery

Dr. JP Arrebola is under contract within the Ramón y Cajal Program (RYC-2016-20155, Ministerio de Economía, Industria y Competitividad, Spain). This study was supported by research grants from Instituto de Salud Carlos III, Junta de Andalucía and European Regional Development Fund – FEDER (PI-0513/2012, PI16/01858, PI18/01573, PI20/01568).Chronic exposure to persistent organic pollutants (POPs) is suspected to contribute to the onset of breast cancer, but the impact on the evolution of patients after diagnosis is unclear. We aimed to analyze the contribution of long-term exposure to five POPs to overall mortality, cancer recurrence, metastasis, and development of second primary tumors over a global follow-up of 10 years after surgery in breast cancer patients in a cohort study. Between 2012 and 2014, a total of 112 newly diagnosed breast cancer patients were recruited from a public hospital in Granada, Southern Spain. Historical exposure to POPs was estimated by analyzing their concentrations in breast adipose tissue samples. Sociodemographic data were collected through face-to-face interviews, while data on evolution tumor were retrieved from clinical records. Statistical analyses were performed using Cox regression (overall survival, breast cancer recurrence or metastasis) and binary logistic regression models (joint outcome variable). We also tested for statistical interactions of POPs with age, residence, and prognostic markers. The third vs first tertile of hexachlorobenzene concentrations was associated with a lower risk of all-cause mortality (Hazard Ratio, HR = 0.26; 95 % Confidence Interval, CI = 0.07-0.92) and of the appearance of any of the four events (Odds Ratio = 0.37; 95 % CI = 0.14-1.03). Polychlorinated biphenyl 138 concentrations were significantly and inversely associated with risk of metastasis (HR = 0.65; 95 % CI = 0.44-0.97) and tumor recurrence (HR = 0.69; 95 % CI = 0.49-0.98). Additionally, p,p & PRIME;dichlorodiphenyldichloroethylene showed inverse associations with risk of metastasis in women with ER-positive tumors (HR = 0.49; 95 % CI = 0.25-0.93) and in those with a tumor size <2.0 cm (HR = 0.39; 95 % CI = 0.18-0.87).Ministerio de Economía, Industria y Competitividad, Spain RYC-2016-20155Instituto de Salud Carlos IIIJunta de AndalucíaEuropean Regional Development Fund – FEDER (PI-0513/2012, PI16/01858, PI18/01573, PI20/01568)University of Granada / CBU

α,γ-Peptide nanotube templating of one-dimensional parallel fullerene arrangements

(Figure Presented) The formation and full characterization of single self-assembling α,γ-peptide nanotubes (α,γ-SPNs) is described. The introduction of C60 into cyclic peptides allows the preparation of supramolecular 1D fullerene arrangements induced by peptide nanotube formation under appropriate conditions. © 2009 American Chemical Society.This work was supported by the Spanish Ministry of Education and Science and the ERDF [SAF2007-61015 and Consolider Ingenio 2010 (CSD2007-00006)] and the Xunta de Galicia (GRC2006/ 132, PGIDIT06PXIB209018PR, PGIDIT08CSA047209PR, and R2006/ 124). The work by J.M.V. and J.L.C. was supported by Grants BFU2007- 62382/BMC from the Spanish MEC (J.M.V.) and S-0505/MAT/0283 from the Madrid Regional Government (J.M.V. and J.L.C.). C.R. and R.J.B. thank the Spanish MEC for their FPU Fellowships. We also thank Dr. Carmen Serra (Nanotechnology and Surface Analysis Service at C.A.C.T.I., University of Vigo) for her help with STM. We also thank Dowpharma for their kind gift of ENZA enzymes used in the preparation of D-Boc-γ-Acp-OH.Peer reviewe

Associations of circulating levels of phthalate metabolites with cytokines and acute phase reactants in a Spanish human cohort

Supplementary data to this article can be found online at https://doi.org/10.1016/j.envres.2022.114470The associations between human phthalate exposure and the onset of chronic diseases with an immunological component (e.g., metabolic syndrome, cancer) remain unclear, partly due to the uncertainties in the underlying mechanisms. This study investigates cross-sectional associations of the concentrations of 10 phthalate metabolites with 19 cytokines and acute phase proteins in 213 serum samples of Spanish adults. The associations were explored by Spearman's correlation, multivariable linear regression, and weighted quantile sum regression analyses. In the multivariable analyses, levels of plasminogen activator inhibitor (PAI)-1 were positively associated with mono-n-butyl phthalate (fold-change per one IQR increase in phthalate levels, 95% Confidence Interval: 1.65, 1.45–1.88) and mono-iso-butyl phthalate (3.07, 2.39–3.95), mono-ethyl phthalate (2.05, 1.62–2.61), as well as categorized mono-iso-decyl and mono-benzyl phthalates. The same phthalates also were significantly associated with leptin, interleukin (IL)-18 and monocyte chemoattractant protein-1. Moreover, the proinflammatory markers IL-1β, IL-17, IL-8, IL-6, IL-12, tumor necrosis factor, and lipopolysaccharide-binding protein showed positive and negative associations with, respectively, mono-(2-ethyl-hexyl) and mono-methyl phthalates. Finally, phthalate mixtures were positively associated with PAI-1, leptin, IL-18, IL-12, IL-8 and IL-1β. Despite the cross-sectional design limitation, these associations point to relevant subclinical immuno-inflammatory actions of these pollutants, warranting confirmation in future studies.Instituto de Salud Carlos III, Spain (grant numbers PI16/01858, PI18/01573, PI20/01568)European Union (ERDF), “A way to make EuropeRamón y Cajal Program (RYC- 2016-20155, Ministerio de Economía, Industria y Competitividad, Spain),PFIS (FI17/ 00310, Pre-doctoral Health Research Training Contracts, Instituto de Salud Carlos III, Spain)PFIS (FI21/00269, Pre-doctoral Health Research Training Contracts, Instituto de Salud Carlos III, Spain

Public healthcare costs associated with long-term exposure to mixtures of persistent organic pollutants in two areas of Southern Spain: A longitudinal analysis

Background: Polychlorinated biphenyls and organochlorine pesticides are persistent organic pollutants (POPs) that had been banned or restricted in many countries, including Spain. However, their ubiquity still poses environmental and human health threats. Objective: To longitudinally explore public healthcare costs associated with long-term exposure to a mixture of 8 POPs in a cohort of residents of two areas of Granada Province, Southern Spain. Methods: Longitudinal study in a subsample (n = 385) of GraMo adult cohort. Exposure assessment was performed by analyzing adipose tissue POP concentrations at recruitment. Average primary care (APC) and average hospital care (AHC) expenditures of each participant over 14 years were estimated using the data from their medical records. Data analyses were performed by robust MM regression, weighted quantile sum regression (WQS) and G-computation analysis. Results: In the adjusted robust MM models for APC, most POPs showed positive beta coefficients, being Hexachlorobenzene (HCB) significantly associated (beta 1.87; 95% Confidence interval (95%CI): 0.17, 3.57). The magnitude of this association increased (beta: 3.72; 95%CI: 0.80, 6.64) when the analyses were restricted to semirural residents, where p-HCH was also marginally-significantly associated to APC (beta: 3.40; 95%CI: -0.10, 6.90). WQS revealed a positive but non-significant mixture association with APC (beta: 0.14; 95%CI: -0.06, 0.34), mainly accounted for by p-HCH (54%) and HCB (43%), that was borderline-significant in the semi-rural residents (beta: 0.23; 95%CI: -0.01, 0.48). No significant results were observed in G-Computation analyses. Conclusion: Long-term exposure to POP mixtures might represent a modifiable factor increasing healthcare costs, thus affecting the efficiency of the healthcare systems. However, and owing the complexity of the potential causal pathways and the limitations of the present study, further research is warranted to fully elucidate ascertain whether interventions to reduce human exposure should be considered in healthcare policies.CIBER de Epidemiologia y Salud Publica (CIBERESP), Instituto de Salud Carlos III, Spain PI16/01858 PI18/01573 PI20/01568European CommissionRamon y Cajal Program (Ministerio de Economia, Industria y Competitividad, Spain) RYC-2016-20,155PFIS (Instituto de Salud Carlos III, Spain) FI17/00310Universidad de Granada/CBU

Pilot multi-omic analysis of human bile from benign and malignant biliary strictures: a machine-learning approach

Cholangiocarcinoma (CCA) and pancreatic adenocarcinoma (PDAC) may lead to the development of extrahepatic obstructive cholestasis. However, biliary stenoses can also be caused by benign conditions, and the identification of their etiology still remains a clinical challenge. We performed metabolomic and proteomic analyses of bile from patients with benign (n = 36) and malignant conditions, CCA (n = 36) or PDAC (n = 57), undergoing endoscopic retrograde cholangiopancreatography with the aim of characterizing bile composition in biliopancreatic disease and identifying biomarkers for the differential diagnosis of biliary strictures. Comprehensive analyses of lipids, bile acids and small molecules were carried out using mass spectrometry (MS) and nuclear magnetic resonance spectroscopy (1H-NMR) in all patients. MS analysis of bile proteome was performed in five patients per group. We implemented artificial intelligence tools for the selection of biomarkers and algorithms with predictive capacity. Our machine-learning pipeline included the generation of synthetic data with properties of real data, the selection of potential biomarkers (metabolites or proteins) and their analysis with neural networks (NN). Selected biomarkers were then validated with real data. We identified panels of lipids (n = 10) and proteins (n = 5) that when analyzed with NN algorithms discriminated between patients with and without cancer with an unprecedented accuracy.This research was funded by: Instituto de Salud Carlos III (ISCIII) co-financed by Fondo Europeo de Desarrollo Regional (FEDER) Una manera de hacer Europa, grant numbers: PI16/01126 (M.A.A.), PI19/00819 (M.J.M. and J.J.G.M.), PI15/01132, PI18/01075 and Miguel Servet Program CON14/00129 (J.M.B.); Fundación Científica de la Asociación Española Contra el Cáncer (AECC Scientific Foundation), grant name: Rare Cancers 2017 (J.M.U., M.L.M., J.M.B., M.J.M., R.I.R.M., M.G.F.-B., C.B., M.A.A.); Gobierno de Navarra Salud, grant number 58/17 (J.M.U., M.A.A.); La Caixa Foundation, grant name: HEPACARE (C.B., M.A.A.); AMMF The Cholangiocarcinoma Charity, UK, grant number: 2018/117 (F.J.C. and M.A.A.); PSC Partners US, PSC Supports UK, grant number 06119JB (J.M.B.); Horizon 2020 (H2020) ESCALON project, grant number H2020-SC1-BHC-2018–2020 (J.M.B.); BIOEF (Basque Foundation for Innovation and Health Research: EiTB Maratoia, grant numbers BIO15/CA/016/BD (J.M.B.) and BIO15/CA/011 (M.A.A.). Department of Health of the Basque Country, grant number 2017111010 (J.M.B.). La Caixa Foundation, grant number: LCF/PR/HP17/52190004 (M.L.M.), Mineco-Feder, grant number SAF2017-87301-R (M.L.M.), Fundación BBVA grant name: Ayudas a Equipos de Investigación Científica Umbrella 2018 (M.L.M.). MCIU, grant number: Severo Ochoa Excellence Accreditation SEV-2016-0644 (M.L.M.). Part of the equipment used in this work was co-funded by the Generalitat Valenciana and European Regional Development Fund (FEDER) funds (PO FEDER of Comunitat Valenciana 2014–2020). Gobierno de Navarra fellowship to L.C. (Leticia Colyn); AECC post-doctoral fellowship to M.A.; Ramón y Cajal Program contracts RYC-2014-15242 and RYC2018-024475-1 to F.J.C. and M.G.F.-B., respectively. The generous support from: Fundación Eugenio Rodríguez Pascual, Fundación Echébano, Fundación Mario Losantos, Fundación M Torres and Mr. Eduardo Avila are acknowledged. The CNB-CSIC Proteomics Unit belongs to ProteoRed, PRB3-ISCIII, supported by grant PT17/0019/0001 (F.J.C.). Comunidad de Madrid Grant B2017/BMD-3817 (F.J.C.).Peer reviewe

Treatment with tocilizumab or corticosteroids for COVID-19 patients with hyperinflammatory state: a multicentre cohort study (SAM-COVID-19)

Objectives: The objective of this study was to estimate the association between tocilizumab or corticosteroids and the risk of intubation or death in patients with coronavirus disease 19 (COVID-19) with a hyperinflammatory state according to clinical and laboratory parameters. Methods: A cohort study was performed in 60 Spanish hospitals including 778 patients with COVID-19 and clinical and laboratory data indicative of a hyperinflammatory state. Treatment was mainly with tocilizumab, an intermediate-high dose of corticosteroids (IHDC), a pulse dose of corticosteroids (PDC), combination therapy, or no treatment. Primary outcome was intubation or death; follow-up was 21 days. Propensity score-adjusted estimations using Cox regression (logistic regression if needed) were calculated. Propensity scores were used as confounders, matching variables and for the inverse probability of treatment weights (IPTWs). Results: In all, 88, 117, 78 and 151 patients treated with tocilizumab, IHDC, PDC, and combination therapy, respectively, were compared with 344 untreated patients. The primary endpoint occurred in 10 (11.4%), 27 (23.1%), 12 (15.4%), 40 (25.6%) and 69 (21.1%), respectively. The IPTW-based hazard ratios (odds ratio for combination therapy) for the primary endpoint were 0.32 (95%CI 0.22-0.47; p < 0.001) for tocilizumab, 0.82 (0.71-1.30; p 0.82) for IHDC, 0.61 (0.43-0.86; p 0.006) for PDC, and 1.17 (0.86-1.58; p 0.30) for combination therapy. Other applications of the propensity score provided similar results, but were not significant for PDC. Tocilizumab was also associated with lower hazard of death alone in IPTW analysis (0.07; 0.02-0.17; p < 0.001). Conclusions: Tocilizumab might be useful in COVID-19 patients with a hyperinflammatory state and should be prioritized for randomized trials in this situatio