Self-assembly, binding ability and magnetic properties of dicopper(ii) pyrazolenophanes

A novel series of dinuclear copper(II) pyrazolenophanes of the formula [Cu-2(mu-4-Mepz)(2)(mu-ClO4)(ClO4)(bpm)(2)] (1), [Cu-2(mu-pz)(2)(mu-H2O)(ClO4)(4,7-Me(2)phen)(2)]ClO4 center dot H2O center dot CH3CN (2), [Cu-2(mu-pz)(2)(mu-H2O)(ClO4)(3/2)(H2O)(1/2)(phen)(2)](2)[Cu-2(mu-pz)(2)(mu-ClO4)(ClO4)(2)(phen)(2)]center dot 8H(2)O (3), and [Cu-2(mu-pz)(2)(CH3CN)(2)(3,4,7,8-Me(4)phen)(2)](ClO4)(2) (4) (Hpz = pyrazole, H-4-Mepz = 4-methylpyrazole, bpm = 2,2'-bipyrimidine, phen = 1,10-phenanthroline, 4,7-Me(2)phen = 4,7-dimethyl-1,10-phenanthroline, and 3,4,7,8-Me(4)phen = 3,4,7,8-tetramethyl-1,10-phenanthroline) have been synthesized and magneto-structurally investigated. The crystal structures of 1-4 contain bis(pyrazolate)(perchlorate)-(1 and 3), bis(pyrazolate)(aqua)-(2 and 3), or bis(pyrazolate)-bridged (4) dicopper(II) entities of the metallacyclophane-type with bpm (1), 4,7-Me(2)phen (2), phen (3), and 3,4,7,8-Me(4)phen (4) as blocking bidentate ligands. All of them exhibit a saddle conformation with an overall not planar but bent, six-membered Cu-(N-N')(2)-Cu metallacyclic core with relatively short intermetallic distances across the bis(pyrazolate)(perchlorate) [r = 3.3076(5) (1) and 3.382(1) angstrom (3)], bis(pyrazolate)(aqua) [r = 3.383(1) (2) and 3.357(1) angstrom (3)], and bis(pyrazolate) bridges [r = 3.098(1) angstrom (4)]. The analyses of the variable-temperature magnetic susceptibility of 1-4 reveal the occurrence of a moderately strong antiferromagnetic coupling across the bis(pyrazolate)(perchlorate) [-J = 228 (1) and 193 cm(-1) (3)], bis(pyrazolate)(aqua) [-J = 189 (2) and 221 cm(-1) (3)], and bis(pyrazolate) bridges [-J = 197 cm(-1) (4)] (the spin Hamiltonian being defined as H = -JS(1).S-2 with S-1 = S-2 = S-Cu = 1/2).A novel series of dinuclear copper(II) pyrazolenophanes of the formula [Cu2(μ-4-Mepz)2(μ-ClO4)(ClO4)(bpm)2] (1), [Cu2(μ-pz)2(μ-H2O)(ClO4)(4,7-Me2phen)2]ClO4·H2O·CH3CN (2), [Cu2(μ-pz)2(μ-H2O)(ClO4)3/2(H2O)1/2(phen)2]2[Cu2(μ-pz)2(μ-ClO4)(ClO4)2(phen)2]·8H2O183437449COORDENAÇÃO DE APERFEIÇOAMENTO DE PESSOAL DE NÍVEL SUPERIOR - CAPESsem informaçãoThis work was supported by the Ministerio Español de Economía y Competitividad (Project CTQ2013-44844P and Unidad de Excelencia MDM-2015-0538) and the Generalitat Valenciana (PROMETEOII/2014/070). We also acknowledge the financial support from Brazilian

Social, Clinical and Microbiological Differential Characteristics of Tuberculosis among Immigrants in Spain

BACKGROUND: To identify the differential tuberculosis (TB) characteristics within the immigrant population with respect to natives in Spain. METHODOLOGY/PRINCIPAL FINDINGS: A prospective cohort study design was implemented to examine the TB cases diagnosed and starting standard antituberculous treatment in Spain, between January 1st 2006 and March 31st 2007. A logistic regression analysis was performed to determine differential characteristics. 1,490 patients were included in the study population, 1,048 natives and 442 (29.7%) immigrants. According to the multivariate analysis, the following variables were significantly associated with immigrant TB cases: younger age (OR = 3.79; CI:2.16-6.62), living in group situation (OR = 7.61; CI:3.38-12.12), lower frequency of disabled (OR:0.08; CI:0.02-0.26) and retired (OR:0.21; CI:0.09-0.48) employment status, lower frequency of pulmonary disease presentation (OR = 0.47; CI:0.24-0.92), primary or emergency care admission (OR = 1.80; CI:1.05-3.06 and OR = 2.16; CI:1.36-3.45), drug resistance (OR = 1.86; CI:1.01-3.46), treatment default (OR:2.12; CI:1.18-3.81), lower frequency of alcohol and cigarette consumption (OR = 2.10; CI:1.42-3.11 and OR = 2.85; CI:2.10-3.87 respectively), more directly observed treatment (OR = 1.68; CI:1.04-2.69), and poor understanding of TB disease and its treatment (OR = 3.11; CI:1.86-5.20). The low percentage of primary MDR-TB in the native population (0.1% vs. 2.2% of immigrants) should be noted. CONCLUSIONS/SIGNIFICANCE: The differences show the need to introduce specific strategies in the management of TB within the immigrant population, including the improvement of social and work conditions

The anti-aging factor Klotho protects against acquired long QT syndrome induced by uremia and promoted by fibroblast growth factor 23

[Background]: Chronic kidney disease (CKD) is associated with increased propensity for arrhythmias. In this context, ventricular repolarization alterations have been shown to predispose to fatal arrhythmias and sudden cardiac death. Between mineral bone disturbances in CKD patients, increased fibroblast growth factor (FGF) 23 and decreased Klotho are emerging as important effectors of cardiovascular disease. However, the relationship between imbalanced FGF23-Klotho axis and the development of cardiac arrhythmias in CKD remains unknown. [Methods]: We carried out a translational approach to study the relationship between the FGF23–Klotho signaling axis and acquired long QT syndrome in CKD-associated uremia. FGF23 levels and cardiac repolarization dynamics were analyzed in patients with dialysis-dependent CKD and in uremic mouse models of 5/6 nephrectomy (Nfx) and Klotho deficiency (hypomorphism), which show very high systemic FGF23 levels. [Results]: Patients in the top quartile of FGF23 levels had a higher occurrence of very long QT intervals (> 490 ms) than peers in the lowest quartile. Experimentally, FGF23 induced QT prolongation in healthy mice. Similarly, alterations in cardiac repolarization and QT prolongation were observed in Nfx mice and in Klotho hypomorphic mice. QT prolongation in Nfx mice was explained by a significant decrease in the fast transient outward potassium (K+) current (Itof), caused by the downregulation of K+ channel 4.2 subunit (Kv4.2) expression. Kv4.2 expression was also significantly reduced in ventricular cardiomyocytes exposed to FGF23. Enhancing Klotho availability prevented both long QT prolongation and reduced Itof current. Likewise, administration of recombinant Klotho blocked the downregulation of Kv4.2 expression in Nfx mice and in FGF23-exposed cardiomyocytes. [Conclusion]: The FGF23–Klotho axis emerges as a new therapeutic target to prevent acquired long QT syndrome in uremia by minimizing the predisposition to potentially fatal ventricular arrhythmias and sudden cardiac death in patients with CKD.This work was supported by projects from the Instituto de Salud Carlos III, Ministry of Economy, Industry and Competitiveness (PI17/01093, PI17/01193, PI20/00763, CP15/00129, F18/00261, CPII20/00022, SAF2017-84777-R, PID2020-113238RB-I00), from the Sociedad Española de Cardiología (SEC), and from the Fundación Renal Íñigo Alvarez de Toledo (FRIAT), co-funded by the European Regional Development Fund (Fondos FEDER)

Aplicación de nuevas técnicas docentes en la asignatura Sistemas Cliente/Servidor

En este trabajo mostramos nuestras experiencias en la aplicación de metodologías de aprendizaje cooperativo y basado en proyectos en la asignatura Sistemas Cliente/Servidor en los cursos académicos 2008/2009 y 2009/2010

Reuse of terminological resources for efficient ontological engineering in Life Sciences

This paper is intended to explore how to use terminological resources for ontology engineering. Nowadays there are several biomedical ontologies describing overlapping domains, but there is not a clear correspondence between the concepts that are supposed to be equivalent or just similar. These resources are quite precious but their integration and further development are expensive. Terminologies may support the ontological development in several stages of the lifecycle of the ontology; e.g. ontology integration. In this paper we investigate the use of terminological resources during the ontology lifecycle. We claim that the proper creation and use of a shared thesaurus is a cornerstone for the successful application of the Semantic Web technology within life sciences. Moreover, we have applied our approach to a real scenario, the Health-e-Child (HeC) project, and we have evaluated the impact of filtering and re-organizing several resources. As a result, we have created a reference thesaurus for this project, named HeCTh

Uso de los museos de Madrid para el estudio de la evolución de los conceptos de “ciudadanía”, “audiencias” y “opinión pública” en estudios de grado y de postgrado de la Universidad Complutense

Proyecto de mejora de recursos disponibles para la docencia. El proyecto muestra la experiencia de aprovechar recursos de museos cercanos a las aulas de la Ciudad Universitaria de Madrid para explicar y ejemplificar críticamente la evolución histórica de conceptos-clave en Ciencias Sociales. En concreto se ha trabajado con los conceptos de ciudadanía, audiencias y opinión pública

Autoimagen en las dos primeras fases de la adolescencia y factores relacionados

Se trata de la descripción de la imagen corporal en un amplio grupo de alumnos escolarizados en Cantabria (n=1179 adolescentes), de 10 a 17 años de edad (adolescencia temprana e intermedia) dentro de un estudio más amplio encaminado a evidenciar un estilo de vida saludable en estos adolescentes, llevado a cabo por profesores de universidad y profesores de educación física de los centros educativos. Los principales hallazgos consisten en que los adolescentes tienen, en general, una buena imagen de sí mismos y, aunque no reconocen la elevada prevalencia de sobrepeso y obesidad, desean adelgazar y el grado de satisfacción que tienen con su imagen corporal va empeorando conforme avanza la adolescencia, signifi cativamente más en las del sexo femenino. Esta insatisfacción debe ser tenida en cuenta en el abordaje de los adolescentes con obesidad

The Fourteenth Data Release of the Sloan Digital Sky Survey: First Spectroscopic Data from the extended Baryon Oscillation Spectroscopic Survey and from the second phase of the Apache Point Observatory Galactic Evolution Experiment

The fourth generation of the Sloan Digital Sky Survey (SDSS-IV) has been in operation since July 2014. This paper describes the second data release from this phase, and the fourteenth from SDSS overall (making this, Data Release Fourteen or DR14). This release makes public data taken by SDSS-IV in its first two years of operation (July 2014-2016). Like all previous SDSS releases, DR14 is cumulative, including the most recent reductions and calibrations of all data taken by SDSS since the first phase began operations in 2000. New in DR14 is the first public release of data from the extended Baryon Oscillation Spectroscopic Survey (eBOSS); the first data from the second phase of the Apache Point Observatory (APO) Galactic Evolution Experiment (APOGEE-2), including stellar parameter estimates from an innovative data driven machine learning algorithm known as "The Cannon"; and almost twice as many data cubes from the Mapping Nearby Galaxies at APO (MaNGA) survey as were in the previous release (N = 2812 in total). This paper describes the location and format of the publicly available data from SDSS-IV surveys. We provide references to the important technical papers describing how these data have been taken (both targeting and observation details) and processed for scientific use. The SDSS website (www.sdss.org) has been updated for this release, and provides links to data downloads, as well as tutorials and examples of data use. SDSS-IV is planning to continue to collect astronomical data until 2020, and will be followed by SDSS-V.Comment: SDSS-IV collaboration alphabetical author data release paper. DR14 happened on 31st July 2017. 19 pages, 5 figures. Accepted by ApJS on 28th Nov 2017 (this is the "post-print" and "post-proofs" version; minor corrections only from v1, and most of errors found in proofs corrected

Evidence for classification of c.1852_1853AA>GC in MLH1 as a neutral variant for Lynch syndrome

Background: Lynch syndrome (LS) is an autosomal dominant inherited cancer syndrome characterized by early onset cancers of the colorectum, endometrium and other tumours. A significant proportion of DNA variants in LS patients are unclassified. Reports on the pathogenicity of the c.1852_1853AA>GC (p.Lys618Ala) variant of the MLH1 gene are conflicting. In this study, we provide new evidence indicating that this variant has no significant implications for LS. Methods: The following approach was used to assess the clinical significance of the p.Lys618Ala variant: frequency in a control population, case-control comparison, co-occurrence of the p.Lys618Ala variant with a pathogenic mutation, co-segregation with the disease and microsatellite instability in tumours from carriers of the variant. We genotyped p.Lys618Ala in 1034 individuals (373 sporadic colorectal cancer [CRC] patients, 250 index subjects from families suspected of having LS [revised Bethesda guidelines] and 411 controls). Three well-characterized LS families that fulfilled the Amsterdam II Criteria and consisted of members with the p.Lys618Ala variant were included to assess co-occurrence and co-segregation. A subset of colorectal tumour DNA samples from 17 patients carrying the p.Lys618Ala variant was screened for microsatellite instability using five mononucleotide markers. Results: Twenty-seven individuals were heterozygous for the p.Lys618Ala variant; nine had sporadic CRC (2.41%), seven were suspected of having hereditary CRC (2.8%) and 11 were controls (2.68%). There were no significant associations in the case-control and case-case studies. The p.Lys618Ala variant was co-existent with pathogenic mutations in two unrelated LS families. In one family, the allele distribution of the pathogenic and unclassified variant was in trans, in the other family the pathogenic variant was detected in the MSH6 gene and only the deleterious variant co-segregated with the disease in both families. Only two positive cases of microsatellite instability (2/17, 11.8%) were detected in tumours from p.Lys618Ala carriers, indicating that this variant does not play a role in functional inactivation of MLH1 in CRC patients. Conclusions: The p.Lys618Ala variant should be considered a neutral variant for LS. These findings have implications for the clinical management of CRC probands and their relatives.Generalitat Valenciana in Spain (AP140/08) and the Biomedical Research Foundation from the Hospital of Elche, Spain (FIBElx0902). Conselleria de Educació (Generalitat Valenciana); Fundacion Juan Peran-Pikolinos; Fundacion Carolina-BBVA and Fondo Investigación Sanitaria (FI07/00303). Instituto de Salud Carlos III (INT09/208)

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London