Interaction of Variable Bacterial Outer Membrane Lipoproteins with Brain Endothelium

Previously we reported that the variable outer membrane lipoprotein Vsp1 from the relapsing fever spirochete Borrelia turicatae disseminates from blood to brain better than the closely related Vsp2 [1]. Here we studied the interaction between Vsp1 and Vsp2 with brain endothelium in more detail.We compared Vsp1 to Vsp2 using human brain microvascular endothelial cell (HBMEC) association assays with aminoacid radiolabeled Vsp-expressing clones of recombinant Borrelia burgdorferi and lanthanide-labeled purified lipidated Vsp1 (LVsp1) and Vsp2 (LVsp2) and inoculations of the lanthanide-labeled proteins into mice. The results showed that heterologous expression of LVsp1 or LVsp2 in B. burgdorferi increased its association with HBMEC to a similar degree. Purified lanthanide-labeled lipidated Vsp1 (LVsp1) and LVsp2 by themselves were capable of associating with HBMEC. The association of LVsp1 with brain endothelium was time-dependent, saturable, and required the lipidation. The association of Vsp1 with HBMEC was inhibited by incubation at lower temperature or with excess unlabeled LVsp1 or LVsp2 but not with excess rVsp1 or mouse albumin or an anti Vsp1 monoclonal antibody. The association of LVsp2 with HBMEC and its movement from blood to brain parenchyma significantly increased in the presence of LVsp1.Variable bacterial outer membrane lipoproteins interact with brain endothelium differently; the lipidation and variable features at the protein dome region are key modulators of this interaction

Coping Strategies Used by Female Victims of the Colombian Armed Conflict: The Women in the Colombian Conflict (MUCOCO) Program

The effects of armed conflict on women in post-conflict situations are an area of analysis for social disciplines. This study will analyze the situation in Colombia, currently involved in a peace restoration process. The aim is to verify the efficacy of a coping and emotion regulation program analyzing victimization as well as the coping strategies employed in response to these violent acts. The program focuses on 62 women contacted through the Ruta Pacífica de las Mujeres, a nongovernmental organization. The program had a positive effect on women, reporting lower levels of posttraumatic stress, more functional coping strategies, and less use of dysfunctional strategies. All emotional cognitive and social indicators improved. Women felt emotionally better, perceiving greater social support and more trust in institutions. Survivors had more self-confidence to achieve their goals and solve their problems. The implications in a context of peace reconstruction and search for social cohesion are discussed.project (Proyectos CUD 2017) funded by the Oficina de Cooperación al Desarrollo (Development Cooperation Office) of the Universidad del País Vasco/Euskal Herriko Unibertsitatea (University of the Basque Country, Spain) and the University of Burgos funding for the research group SIQoL (Y133GI)

Aprendizaje en semiología radiológica para Tecnólogos en Radiología de la Fundación Universitaria del Área Andina, mediante una herramienta informática

La Semiología es una materia compleja que se enseña desde diversas metodologías, lo cual la hace de alto esfuerzo académico para los estudiantes que la requieren en el desarrollo de su actividad. Se ha encontrado que la literatura sobre Semiología Radiológica está dirigida al Médico Radiólogo, lo cual genera un inconveniente para el Tecnólogo en Radiología debido al enfoque, extensión y profundidad de los temas encaminados al diagnóstico y el tratamiento. El uso de las Tecnologías de Información y Comunicación (TIC), facilitan a los docentes la enseñanza de la semiología, y de esta manera el aprendizaje de esta para los estudiantes, simplificando así la comprensión de la información y el acceso a la misma. Por medio de esta investigación se plantea que, a partir de la implementación de la herramienta informática se producirán diferencias significativas entre el postest y el pretest (intra-grupos) y los sujetos de un grupo experimental

Barriers to Coordination? Examining the Impact of Culture on International Mediation Occurrence and Effectiveness

‘Culture’ features prominently in the literature on international mediation: if belligerents share cultural characteristics, they are likely to have a common understanding and norms. This creates a common identity and makes coordination less costly, which ultimately facilitates mediation occurrence and effectiveness. Surprisingly, existing quantitative research largely neglects any cultural ties the antagonists might share with the mediator. This article addresses this gap by offering one of the first joint analyses of fighting parties’ and mediators’ culture – and the interaction thereof. Based on existing work, a theoretical framework for mediation occurrence and effectiveness is developed and innovative measures for belligerents’ cultural ties and the links to the mediator are used. Contrary to expectations the results suggest that larger cultural distances between antagonists make mediation more likely, while cultural dissimilarities between them and the mediator have the opposite effect. Evidence is also found for a conditional effect between the two culture variables on mediation occurrence

Longitudinal outcomes of obeticholic acid therapy in ursodiol-nonresponsive primary biliary cholangitis: Stratifying the impact of add-on fibrates in real-world practice

Background Suboptimal response to ursodeoxycholic acid occurs in 40% of primary biliary cholangitis (PBC) patients, affecting survival. Achieving a deep response (normalisation of alkaline phosphatase [ALP] and bilirubin ≤0.6 upper limit of normal) improves survival. Yet, the long-term effectiveness of second-line treatments remains uncertain. Aims To evaluate the long-term effectiveness of obeticholic acid (OCA) ± fibrates. Focusing on biochemical response (ALP ≤1.67 times the upper limit of normal, with a decrease of at least 15% from baseline and normal bilirubin levels), normalisation of ALP, deep response and biochemical remission (deep response plus aminotransferase normalisation). Methods We conducted a longitudinal, observational, multicentre study involving ursodeoxyccholic acid non-responsive PBC patients (Paris-II criteria) from Spain and Portugal who received OCA ± fibrates. Results Of 255 patients, median follow-up was 35.1 months (IQR: 20.2–53). The biochemical response in the whole cohort was 47.2%, 61.4% and 68.6% at 12, 24 and 36 months. GLOBE-PBC and 5-year UK-PBC scores improved (p < 0.001). Triple therapy (ursodeoxycholic acid plus OCA plus fibrates) had significantly higher response rates than dual therapy (p = 0.001), including ALP normalisation, deep response and biochemical remission (p < 0.001). In multivariate analysis, triple therapy remained independently associated with biochemical response (p = 0.024), alkaline phosphatase normalisation, deep response and biochemical remission (p < 0.001). Adverse effects occurred in 41.2% of cases, leading to 18.8% discontinuing OCA. Out of 55 patients with cirrhosis, 12 developed decompensation. All with baseline portal hypertension. Conclusion Triple therapy was superior in achieving therapeutic goals in UDCA-nonresponsive PBC. Decompensation was linked to pre-existing portal hypertension

A cooperative interaction between LPHN3 and 11q doubles the risk for ADHD

In previous studies of a genetic isolate, we identified significant linkage of attention deficit hyperactivity disorder (ADHD) to 4q, 5q, 8q, 11q and 17p. The existence of unique large size families linked to multiple regions, and the fact that these families came from an isolated population, we hypothesized that two-locus interaction contributions to ADHD were plausible. Several analytical models converged to show significant interaction between 4q and 11q (P<1 × 10−8) and 11q and 17p (P<1 × 10−6). As we have identified that common variants of the LPHN3 gene were responsible for the 4q linkage signal, we focused on 4q–11q interaction to determine that single-nucleotide polymorphisms (SNPs) harbored in the LPHN3 gene interact with SNPs spanning the 11q region that contains DRD2 and NCAM1 genes, to double the risk of developing ADHD. This interaction not only explains genetic effects much better than taking each of these loci effects by separated but also differences in brain metabolism as depicted by proton magnetic resonance spectroscopy data and pharmacogenetic response to stimulant medication. These findings not only add information about how high order genetic interactions might be implicated in conferring susceptibility to develop ADHD but also show that future studies of the effects of genetic interactions on ADHD clinical information will help to shape predictive models of individual outcome

p38 MAPK and JNK Antagonistically Control Senescence and Cytoplasmic p16INK4A Expression in Doxorubicin-Treated Endothelial Progenitor Cells

Patients treated with low-dose anthracyclines often show late onset cardiotoxicity. Recent studies suggest that this form of cardiotoxicity is the result of a progenitor cell disease. In this study we demonstrate that Cord Blood Endothelial Progenitor Cells (EPCs) exposed to low, sub-apoptotic doses of doxorubicin show a senescence phenotype characterized by increased SA-b-gal activity, decreased TRF2 and chromosomal abnormalities, enlarged cell shape, and disarrangement of F-actin stress fibers accompanied by impaired migratory ability. P16 INK4A localizes in the cytoplasm of doxorubicin-induced senescent EPCs and not in the nucleus as is the case in EPCs rendered senescent by different stimuli. This localization together with the presence of an arrest in G2, and not at the G1 phase boundary, which is what usually occurs in response to the cell cycle regulatory activity of p16INK4A, suggests that doxorubicin-induced p16 INK4A does not regulate the cell cycle, even though its increase is closely associated with senescence. The effects of doxorubicin are the result of the activation of MAPKs p38 and JNK which act antagonistically. JNK attenuates the senescence, p16 INK4A expression and cytoskeleton remodeling that are induced by activated p38. We also found that conditioned medium from doxorubicin-induced senescent cardiomyocytes does not attract untreated EPCs, unlike conditioned medium from apoptotic cardiomyocytes which has a strong chemoattractant capacity. In conclusion, this study provides a better understanding of the senescence of doxorubicin-treated EPCs, which may be helpful in preventing and treating late onset cardiotoxicity