Tetraquarks in a chiral constituent quark model

We analyze the possibility of heavy-light tetraquark bound states by means of a chiral constituent quark model. The study is done in a variational approach. Special attention is paid to the contribution given by the different terms of the interacting potential and also to the role played by the different color channels. We find a stable state for both $qq\bar{c}\bar{c}$ and $qq\bar{b}\bar{b}$ configurations. Possible decay modes of these structures are analyzed.Comment: 13 pages, no figures. Accepted for publication in European Journal of Physics

A functional variant of TLR10 modifies the activity of NFkB and may help predict a worse prognosis in patients with rheumatoid arthritis

Background: Toll-like receptor (TLR) family members are key players in inflammation. TLR10 has been poorly studied in chronic inflammatory disorders, and its clinical relevance in rheumatoid arthritis (RA) is as yet unknown. We aimed at identifying TLR10 variants within all coding regions of the gene in patients with RA as well as studying their functional and clinical significance. Methods: TLR10 gene variants were studied by performing sequencing of 66 patients with RA and 30 control subjects. A selected variant, I473T, was then analyzed in 1654 patients and 1702 healthy control subjects. The capacity of this TLR10 variant to modify the transcriptional activity of nuclear factor kappa-light-chain-enhancer of activated B cells (NFkB) was determined by using a luciferase reporter assay and analyzing the expression of NFkB target genes by quantitative polymerase chain reaction. Differences between groups were analyzed by using the Mann-Whitney U test and the unpaired two-tailed Student’s t test. Results: We detected ten missense variants in the TLR10 gene and focused on the I473T substitution based on allele frequencies and the predicted functional impact. I473T variant is not associated with susceptibility to RA, but it significantly correlates with erosive disease in patients seropositive for antibodies to citrullinated protein antigens (p = 0.017 in the total cohort and p = 0.0049 in female patients) and with a lower response to infliximab treatment as measured by the change in Disease Activity Score in 28 joints (p = 0.012) and by the European League Against Rheumatism criteria (p = 0.049). Functional studies showed that TLR10 reduced activation of the NFkB inflammatory pathway in hematopoietic cells, whereas the I473T variant lacked this inhibitory capacity. Consistently, after exposure to infliximab, cells expressing the I437T variant showed higher NFkB activity than cells carrying wild-type TLR10. Conclusions: A TLR10 allelic variant, I473T, has impaired NFkB inhibitory activity and is highly associated with disease severity and low response to infliximab in patients with RA

Cardiovascular disease in immune-mediated inflammatory diseases: a cross-sectional analysis of 6 cohorts

Observational study[Abstract] To analyze in several immune-mediated inflammatory diseases (IMIDs) the influence of demographic and clinical-related variables on the prevalence of cardiovascular disease (CVD), and compare their standardized prevalences.Cross-sectional study, including consecutive patients diagnosed with rheumatoid arthritis, psoriatic arthritis, psoriasis, systemic lupus erythematosus, Crohn disease, or ulcerative colitis, from rheumatology, gastroenterology, and dermatology tertiary care outpatient clinics located throughout Spain, between 2007 and 2010. Our main outcome was defined as previous diagnosis of angina, myocardial infarction, peripheral vascular disease, and/or stroke. Bivariate and multivariate logistic and mixed-effects logistic regression models were performed for each condition and the overall cohort, respectively. Standardized prevalences (in subjects per 100 patients, with 95% confidence intervals) were calculated using marginal analysis.We included 9951 patients. For each IMID, traditional cardiovascular risk factors had a different contribution to CVD. Overall, older age, longer disease duration, presence of traditional cardiovascular risk factors, and male sex were independently associated with a higher CVD prevalence. After adjusting for demographic and traditional cardiovascular risk factors, systemic lupus erythematosus exhibited the highest CVD standardized prevalence, followed by rheumatoid arthritis, psoriasis, Crohn disease, psoriatic arthritis, and ulcerative colitis (4.5 [95% confidence interval (CI): 2.2, 6.8], 1.3 [95% CI: 0.8, 1.8], 0.9 [95% CI: 0.5, 1.2], 0.8 [95% CI: 0.2, 1.3], 0.6 [95% CI: 0.2, 1.0], and 0.5 [95% CI: 0.1, 0.8], respectively).Systemic lupus erythematosus, rheumatoid arthritis, and psoriasis are associated with higher prevalence of CVD compared with other IMIDs. Specific prevention programs should be established in subjects affected with these conditions to prevent CVD

The stability and consolidation of the Francoist Regime. The case of Eastern Andalusia, 1936-50

The stabilisation and longevity of Franco’s regime can be explained by the interpenetration of society and the institutions of the ‘New State’ in three overlapping areas: firstly, in the sphere of the shared culture of the community of civil war victors; secondly, through repression, based on the decisive collaboration of those supporting Francoism, which cut short any possible opposition; thirdly, in the socio-economic sphere, where those making up the groups supporting the ‘New State’ would see their personal interests fulfilled. At the same time, the defeated would be ensnared in a maze of misery and silence, abandoning any political concerns and concentrating instead on survival. Accordingly, the regime proved able to win support from a broad range of social groups while also eliminating any signs of opposition.The Spanish Ministerio de Innovación y Ciencia funded the research drawn on for this article (reference HAR2009‐07487)

Longitudinal analysis of blood DNA methylation identifies mechanisms of response to tumor necrosis factor inhibitor therapy in rheumatoid arthritis

[Abstract] Background: Rheumatoid arthritis (RA) is a chronic, immune-mediated inflammatory disease of the joints that has been associated with variation in the peripheral blood methylome. In this study, we aim to identify epigenetic variation that is associated with the response to tumor necrosis factor inhibitor (TNFi) therapy. Methods: Peripheral blood genome-wide DNA methylation profiles were analyzed in a discovery cohort of 62 RA patients at baseline and at week 12 of TNFi therapy. DNA methylation of individual CpG sites and enrichment of biological pathways were evaluated for their association with drug response. Using a novel cell deconvolution approach, altered DNA methylation associated with TNFi response was also tested in the six main immune cell types in blood. Validation of the results was performed in an independent longitudinal cohort of 60 RA patients. Findings: Treatment with TNFi was associated with significant longitudinal peripheral blood methylation changes in biological pathways related to RA (FDR<0.05). 139 biological functions were modified by therapy, with methylation levels changing systematically towards a signature similar to that of healthy controls. Differences in the methylation profile of T cell activation and differentiation, GTPase-mediated signaling, and actin filament organization pathways were associated with the clinical response to therapy. Cell type deconvolution analysis identified CpG sites in CD4+T, NK, neutrophils and monocytes that were significantly associated with the response to TNFi. Interpretation: Our results show that treatment with TNFi restores homeostatic blood methylation in RA. The clinical response to TNFi is associated to methylation variation in specific biological pathways, and it involves cells from both the innate and adaptive immune systems

Does rapid HIV disease progression prior to combination antiretroviral therapy hinder optimal CD4 + T-cell recovery once HIV-1 suppression is achieved?

This article compares trends in CD4 + T-cell recovery and proportions achieving optimal restoration (≥500 cells/μl) after viral suppression following combination antiretroviral therapy (cART) initiation between rapid and nonrapid progressors. We included HIV-1 seroconverters achieving viral suppression within 6 months of cART. Rapid progressors were individuals experiencing at least one CD4 + less than 200 cells/μl within 12 months of seroconverters before cART. We used piecewise linear mixed models and logistic regression for optimal restoration. Of 4024 individuals, 294 (7.3%) were classified as rapid progressors. At the same CD4 + T-cell count at cART start (baseline), rapid progressors experienced faster CD4 + T-cell increases than nonrapid progressors in first month [difference (95% confidence interval) in mean increase/month (square root scale): 1.82 (1.61; 2.04)], which reversed to slightly slower increases in months 1-18 [−0.05 (−0.06; −0.03)] and no significant differences in 18-60 months [−0.003 (−0.01; 0.01)]. Percentage achieving optimal restoration was significantly lower for rapid progressors than nonrapid progressors at months 12 (29.2 vs. 62.5%) and 36 (47.1 vs. 72.4%) but not at month 60 (70.4 vs. 71.8%). These differences disappeared after adjusting for baseline CD4 + T-cell count: odds ratio (95% confidence interval) 0.86 (0.61; 1.20), 0.90 (0.38; 2.17) and 1.56 (0.55; 4.46) at months 12, 36 and 60, respectively. Among people on suppressive antiretroviral therapy, rapid progressors experience faster initial increases of CD4 + T-cell counts than nonrapid progressors, but are less likely to achieve optimal restoration during the first 36 months after cART, mainly because of lower CD4 + T-cell counts at cART initiation

Association of Functional Polymorphisms of KIR3DL1/DS1 With Behçet's Disease

Behçet's disease (BD) is an immune-mediated vasculitis related to imbalances between the innate and adaptive immune response. Infectious agents or environmental factors may trigger the disease in genetically predisposed individuals. HLA-B51 is the genetic factor stronger associated with the disease, although the bases of this association remain elusive. NK cells have also been implicated in the etiopathogenesis of BD. A family of NK receptors, Killer-cell Immunoglobulin-like Receptor (KIR), with a very complex organization, is very important in the education and control of the NK cells by the union to their ligands, most of them, HLA class I molecules. This study aimed to investigate the contribution of certain KIR functional polymorphisms to the susceptibility to BD. A total of 466 BD patients and 444 healthy individuals were genotyped in HLA class I (A, B, and C). The set of KIR genes and the functional variants of KIR3DL1/DS1 and KIR2DS4 were also determined. Frequency of KIR3DL1004 was lower in patients than in controls (0.15 vs. 0.20, P = 0.005, Pc = 0.015; OR = 0.70; 95% CI 0.54-0.90) in both B51 positive and negative individuals. KIR3DL1004, which encodes a misfolded protein, is included in a common telomeric haplotype with only one functional KIR gene, KIR3DL2. Both, KIR3DL1 and KIR3DL2 sense pathogen-associated molecular patterns but they have different capacities to eliminate them. The education of the NK cells depending on the HLA, the balance of KIR3DL1/KIR3DL2 licensed NK cells and the different capacities of these receptors to eliminate pathogens could be involved in the etiopathogenesis of BD

Axis internationalism: Spanish health experts and the Nazi ‘New Europe’, 1939–1945

Many of the forms and practices of interwar internationalism were recreated under the auspices of the Nazi ‘New Europe’. This article will examine these forms of ‘Axis internationalism’ by looking at Spanish health experts' involvement with Nazi Germany during the Second World War. Despite the ambiguous relationship between the Franco regime and the Axis powers, a wide range of Spanish health experts formed close ties with colleagues from Nazi Germany and across Axis and occupied Europe. Many of those involved were relatively conservative figures who also worked with liberal international health organisations in the pre- and post-war eras. Despite their political differences, their opposing attitudes towards eugenics and the tensions caused by German hegemony, Spanish experts were able to rationalise their involvement with Nazi Germany as a mutually-beneficial continuation of pre-war international health cooperation amongst countries united by a shared commitment to modern, ‘totalitarian’ forms of public health. Despite the hostility of Nazi Germany and its European collaborators to both liberal and left-wing forms of internationalism, this phenomenon suggests that the ‘New Europe’ deserves to be studied as part of the wider history of internationalism in general and of international health in particular

Investigación joven con perspectiva de género III

Actas del III Congreso Internacional de Estudios de Género, Perspectivas y Retos de Futuro: Jóvenes Investigadores (Getafe, 13 - 15 de junio de 2018) organizado por el Instituto Universitario de Estudios de Género de la Universidad Carlos III de Madrid

Post-Franco Theatre

In the multiple realms and layers that comprise the contemporary Spanish theatrical landscape, “crisis” would seem to be the word that most often lingers in the air, as though it were a common mantra, ready to roll off the tongue of so many theatre professionals with such enormous ease, and even enthusiasm, that one is prompted to wonder whether it might indeed be a miracle that the contemporary technological revolution – coupled with perpetual quandaries concerning public and private funding for the arts – had not by now brought an end to the evolution of the oldest of live arts, or, at the very least, an end to drama as we know it