The antidepressant effect of hypericum perforatum extract Ze 117 is associated with reduced possibilities of drug interactions than hypericum perforatum extract LI 160.

Hypericum perforatum (HP) is the most extensively investigated medicinal herbs with antidepressant effect. Differences showed by HP extracts in their antidepressant effect and their clinical consequence of HP-drug interactions have been related with HP extract different composition, particularly regarding to their primary ingredients hyperforin and hypericin content. Experimental data and clinical trials have shown that low-hyperforin-content HP has a comparable antidepressant efficacy in the treatment of mild/moderate depression (1) (2). However, hyperforin is responsible for CYP3A4 induction via activation of a nuclear steroid/pregnane and xenobiotic receptor (SXR/PXR) and hypericin is a P-glycoprotein inducing compound (3), which are the main origin of HP-drug interactions. Changes in cytochrome P-450 (CYP-450) activity could modulate the effect of different drugs. Some of the reported interactions are based on findings from in vitro studies but the clinical importance of which remain to be demonstrated. Two different hypericum extracts, Ze 117 and LI 160, which are differently composed, Ze 117 (0.15-0.25% hypericin, 0.5% hyperforin) and LI 160 (0.3% hypericin, 4-6% hyperforin) were checked regarding their antidepressant-like activity vs. classical antidepressants with and without liver CYP 450 enzyme activity modulation by cimetidine. Experimental procedures followed the ECC Directives and were approved by local authorities. Male Wistar rats (n=6 per group, 6 months old, weight 314±25 g, Charles River-Spain) were injected (i.p. once a day) with Ze 117 (20 mg/kg, Zeller AG), LI 160 (20 mg/kg, Lichtwer Pharma AG), imipramine (IMI) (10.9 mg/kg, Novartis SL), fluoxetine (FLU) (5 mg/kg, Lilly and Dista) or saline (SAL), in presence and absence of cimetidine (CIM) (50 mg/kg, Rimsa) during 20 days. The forced swim test (4) was used for the evaluation of the antidepressant-like effect. The opend-field test was used for the evaluation of the motor activity. The total CYP 450 content of the liver was measure using spectrophotometry methods in liver microsomes. Results are expressed as mean±sem and were compared by Student t test and ANOVA test followed by Bonferroni post-test. The drugs antidepressant effect (reduction of the immobility time) ranking order was: i) without cimetidine’s CYP-450 inhibition: IMI 109±33s >Ze 117 163±21s =FLU165±29s >LI 160 201±234s >SAL 224±17s, pLI 160 144±13s >FLU 171±21s >Ze 117 188±10 >SAL 219±20s, pLI 160 >Ze 117 >SAL, p<0.05). LI 160 significantly reduced the liver CYP-450 total content with respect to SAL (-43.3%, p<0.05) while Ze 117 had lower effect (-25.9%, p<0.05). In conclusion, hypericum perforatum extract Ze 117 shows higher antidepressant effect and lower inhibitory effect of the total CYP 450 liver content than hypericum perforatum extract LI 160. Liver CYP 450 inhibition by cimetidine increased the antidepressant of LI 160 but did not modify the antidepressant effect of Ze 117. (1)Fiebich BL, Knörle R, Appel K et al. (2011) Fitoterapia 82(3):474-480. (2)Singer A, Schmidt M, Hauke W et al. (2011) Phytomedicine 18(8-9):739-742. (3)Mannel M. (2004) Drug Saf 27(11):773-797. (4)Castagné V, Moser P, Roux S et al. (2011) Curr Protoc Neurosci 55:8.10A.1-8.10A.14.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech

Factores Pedagógicos que Favorecen el Éxito Escolar en Estudiantes de Enseñanza Postobligatoria

El foco del presente estudio ha sido el éxito escolar: la continuidad, la permanencia en el sistema educativo, lo cual implica transitar de forma adecuada por sus diversas etapas y modalidades formativas. En particular, hemos buscado conocer qué factores pedagógicos -vinculados a los procesos de enseñanza-aprendizaje y a la relación profesor/a-alumno/a- constituyen condiciones favorables para el éxito y la continuidad escolar de chicas y de chicos de enseñanza secundaria postobligatoria (Bachillerato y Ciclos Formativos). Hemos tratado de visibilizar el éxito escolar de chicos y de chicas en la educación secundaria, de analizar las experiencias y las trayectorias de estudiantes que, más allá del periodo obligatorio, dan continuidad a su vida escolar con éxito académico, de prestar atención a las diferencias entre estudiantes de Bachillerato y Ciclos Formativos y, por último, de analizar de forma diferenciada la experiencia de las chicas y de los chicos, indagando en los elementos de la construcción de la subjetividad en ambos sexos. Para ello, hemos trabajado con una muestra intencional de 26 estudiantes (12 chicas y 14 chicos), 16 de Bachillerato y 10 de Ciclos Formativos, seleccionados por sus docentes, en 12 centros urbanos y semiurbanos de Málaga, Sevilla, Granada, Cádiz y Almería. Los datos han sido recogidos a través de entrevistas semiestructuradas, con el apoyo de la técnica de foto-lenguaje y un cuestionario de contexto.Fundación Centro de Estudios Andaluces - [PRY031/11

Genetic landscape of 6089 inherited retinal dystrophies affected cases in Spain and their therapeutic and extended epidemiological implications

Inherited retinal diseases (IRDs), defined by dysfunction or progressive loss of photoreceptors, are disorders characterized by elevated heterogeneity, both at the clinical and genetic levels. Our main goal was to address the genetic landscape of IRD in the largest cohort of Spanish patients reported to date. A retrospective hospital-based cross-sectional study was carried out on 6089 IRD affected individuals (from 4403 unrelated families), referred for genetic testing from all the Spanish autonomous communities. Clinical, demographic and familiar data were collected from each patient, including family pedigree, age of appearance of visual symptoms, presence of any systemic findings and geographical origin. Genetic studies were performed to the 3951 families with available DNA using different molecular techniques. Overall, 53.2% (2100/3951) of the studied families were genetically characterized, and 1549 different likely causative variants in 142 genes were identified. The most common phenotype encountered is retinitis pigmentosa (RP) (55.6% of families, 2447/4403). The most recurrently mutated genes were PRPH2, ABCA4 and RS1 in autosomal dominant (AD), autosomal recessive (AR) and X-linked (XL) NON-RP cases, respectively; RHO, USH2A and RPGR in AD, AR and XL for non-syndromic RP; and USH2A and MYO7A in syndromic IRD. Pathogenic variants c.3386G > T (p.Arg1129Leu) in ABCA4 and c.2276G > T (p.Cys759Phe) in USH2A were the most frequent variants identified. Our study provides the general landscape for IRD in Spain, reporting the largest cohort ever presented. Our results have important implications for genetic diagnosis, counselling and new therapeutic strategies to both the Spanish population and other related populations.This work was supported by the Instituto de Salud Carlos III (ISCIII) of the Spanish Ministry of Health (FIS; PI16/00425 and PI19/00321), Centro de Investigación Biomédica en Red Enfermedades Raras (CIBERER, 06/07/0036), IIS-FJD BioBank (PT13/0010/0012), Comunidad de Madrid (CAM, RAREGenomics Project, B2017/BMD-3721), European Regional Development Fund (FEDER), the Organización Nacional de Ciegos Españoles (ONCE), Fundación Ramón Areces, Fundación Conchita Rábago and the University Chair UAM-IIS-FJD of Genomic Medicine. Irene Perea-Romero is supported by a PhD fellowship from the predoctoral Program from ISCIII (FI17/00192). Ionut F. Iancu is supported by a grant from the Comunidad de Madrid (CAM, PEJ-2017-AI/BMD7256). Marta del Pozo-Valero is supported by a PhD grant from the Fundación Conchita Rábago. Berta Almoguera is supported by a Juan Rodes program from ISCIII (JR17/00020). Pablo Minguez is supported by a Miguel Servet program from ISCIII (CP16/00116). Marta Corton is supported by a Miguel Servet program from ISCIII (CPII17/00006). The funders played no role in study design, data collection, data analysis, manuscript preparation and/or publication decisions

Homérica: estudiar y vivir el mundo griego (2020-2021)

Formación del alumno en la Antigüedad Clásica en doble orientación didáctica: teórica y teatral-artística, en conjunción. La teórica consiste en jornadas de conferencias y la práctica en un montaje teatral mitológico, a cargo de alumnos y profesores

A personalized intervention to prevent depression in primary care: cost-effectiveness study nested into a clustered randomized trial

Abstract Background: Depression is viewed as a major and increasing public health issue, as it causes high distress in the people experiencing it and considerable financial costs to society. Efforts are being made to reduce this burden by preventing depression. A critical component of this strategy is the ability to assess the individual level and profile of risk for the development of major depression. This paper presents the cost-effectiveness of a personalized intervention based on the risk of developing depression carried out in primary care, compared with usual care. Methods: Cost-effectiveness analyses are nested within a multicentre, clustered, randomized controlled trial of a personalized intervention to prevent depression. The study was carried out in 70 primary care centres from seven cities in Spain. Two general practitioners (GPs) were randomly sampled from those prepared to participate in each centre (i.e. 140 GPs), and 3326 participants consented and were eligible to participate. The intervention included the GP communicating to the patient his/her individual risk for depression and personal risk factors and the construction by both GPs and patients of a psychosocial programme tailored to prevent depression. In addition, GPs carried out measures to activate and empower the patients, who also received a leaflet about preventing depression. GPs were trained in a 10- to 15-h workshop. Costs were measured from a societal and National Health care perspective. Qualityadjustedlife years were assessed using the EuroQOL five dimensions questionnaire. The time horizon was 18 months.This work was supported by grants from the Spanish Ministry of Health, the Institute of Health Carlos III (ISCIII) and the European Regional Development Fund (ERDF) ’A way to build Europe’(grant references PS09/02272, PS09/02147, PS09/01095, PS09/00849 and PS09/00461); the Andalusian Council of Health (grant reference PI-0569-2010); the Spanish Network of Primary Care Research ’redIAPP’ (RD06/0018, RD12/0005/0001); the ’Aragón group’ (RD06/0018/0020, RD12/0005/0006); the ’Bizkaya group’ (RD06/0018/0018, RD12/0005/0010); the Castilla-León Group (RD06/0018/0027); the Mental Health (SJD) Barcelona Group (RD06/0018/0017, RD12/0005/0008); and the Mental-Health, Services and Primary Care (SAMSERAP) MálagaGroup (RD06/0018/0039, RD12/0005/0005)

Association Between Preexisting Versus Newly Identified Atrial Fibrillation and Outcomes of Patients With Acute Pulmonary Embolism

Background Atrial fibrillation (AF) may exist before or occur early in the course of pulmonary embolism (PE). We determined the PE outcomes based on the presence and timing of AF. Methods and Results Using the data from a multicenter PE registry, we identified 3 groups: (1) those with preexisting AF, (2) patients with new AF within 2 days from acute PE (incident AF), and (3) patients without AF. We assessed the 90-day and 1-year risk of mortality and stroke in patients with AF, compared with those without AF (reference group). Among 16 497 patients with PE, 792 had preexisting AF. These patients had increased odds of 90-day all-cause (odds ratio [OR], 2.81; 95% CI, 2.33-3.38) and PE-related mortality (OR, 2.38; 95% CI, 1.37-4.14) and increased 1-year hazard for ischemic stroke (hazard ratio, 5.48; 95% CI, 3.10-9.69) compared with those without AF. After multivariable adjustment, preexisting AF was associated with significantly increased odds of all-cause mortality (OR, 1.91; 95% CI, 1.57-2.32) but not PE-related mortality (OR, 1.50; 95% CI, 0.85-2.66). Among 16 497 patients with PE, 445 developed new incident AF within 2 days of acute PE. Incident AF was associated with increased odds of 90-day all-cause (OR, 2.28; 95% CI, 1.75-2.97) and PE-related (OR, 3.64; 95% CI, 2.01-6.59) mortality but not stroke. Findings were similar in multivariable analyses. Conclusions In patients with acute symptomatic PE, both preexisting AF and incident AF predict adverse clinical outcomes. The type of adverse outcomes may differ depending on the timing of AF onset.info:eu-repo/semantics/publishedVersio

O31 Integrative analysis reveals a molecular stratification of systemic autoimmune diseases

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Spatiotemporal Characteristics of the Largest HIV-1 CRF02_AG Outbreak in Spain: Evidence for Onward Transmissions

Background and Aim: The circulating recombinant form 02_AG (CRF02_AG) is the predominant clade among the human immunodeficiency virus type-1 (HIV-1) non-Bs with a prevalence of 5.97% (95% Confidence Interval-CI: 5.41–6.57%) across Spain. Our aim was to estimate the levels of regional clustering for CRF02_AG and the spatiotemporal characteristics of the largest CRF02_AG subepidemic in Spain.Methods: We studied 396 CRF02_AG sequences obtained from HIV-1 diagnosed patients during 2000–2014 from 10 autonomous communities of Spain. Phylogenetic analysis was performed on the 391 CRF02_AG sequences along with all globally sampled CRF02_AG sequences (N = 3,302) as references. Phylodynamic and phylogeographic analysis was performed to the largest CRF02_AG monophyletic cluster by a Bayesian method in BEAST v1.8.0 and by reconstructing ancestral states using the criterion of parsimony in Mesquite v3.4, respectively.Results: The HIV-1 CRF02_AG prevalence differed across Spanish autonomous communities we sampled from (p &lt; 0.001). Phylogenetic analysis revealed that 52.7% of the CRF02_AG sequences formed 56 monophyletic clusters, with a range of 2–79 sequences. The CRF02_AG regional dispersal differed across Spain (p = 0.003), as suggested by monophyletic clustering. For the largest monophyletic cluster (subepidemic) (N = 79), 49.4% of the clustered sequences originated from Madrid, while most sequences (51.9%) had been obtained from men having sex with men (MSM). Molecular clock analysis suggested that the origin (tMRCA) of the CRF02_AG subepidemic was in 2002 (median estimate; 95% Highest Posterior Density-HPD interval: 1999–2004). Additionally, we found significant clustering within the CRF02_AG subepidemic according to the ethnic origin.Conclusion: CRF02_AG has been introduced as a result of multiple introductions in Spain, following regional dispersal in several cases. We showed that CRF02_AG transmissions were mostly due to regional dispersal in Spain. The hot-spot for the largest CRF02_AG regional subepidemic in Spain was in Madrid associated with MSM transmission risk group. The existence of subepidemics suggest that several spillovers occurred from Madrid to other areas. CRF02_AG sequences from Hispanics were clustered in a separate subclade suggesting no linkage between the local and Hispanic subepidemics

A Large-Scale Genetic Analysis Reveals a Strong Contribution of the HLA Class II Region to Giant Cell Arteritis Susceptibility

We conducted a large-scale genetic analysis on giant cell arteritis (GCA), a polygenic immune-mediated vasculitis. A case-control cohort, comprising 1,651 case subjects with GCA and 15,306 unrelated control subjects from six different countries of European ancestry, was genotyped by the Immunochip array. We also imputed HLA data with a previously validated imputation method to perform a more comprehensive analysis of this genomic region. The strongest association signals were observed in the HLA region, with rs477515 representing the highest peak (p = 4.05 × 10−40, OR = 1.73). A multivariate model including class II amino acids of HLA-DRβ1 and HLA-DQα1 and one class I amino acid of HLA-B explained most of the HLA association with GCA, consistent with previously reported associations of classical HLA alleles like HLA-DRB1∗04. An omnibus test on polymorphic amino acid positions highlighted DRβ1 13 (p = 4.08 × 10−43) and HLA-DQα1 47 (p = 4.02 × 10−46), 56, and 76 (both p = 1.84 × 10−45) as relevant positions for disease susceptibility. Outside the HLA region, the most significant loci included PTPN22 (rs2476601, p = 1.73 × 10−6, OR = 1.38), LRRC32 (rs10160518, p = 4.39 × 10−6, OR = 1.20), and REL (rs115674477, p = 1.10 × 10−5, OR = 1.63). Our study provides evidence of a strong contribution of HLA class I and II molecules to susceptibility to GCA. In the non-HLA region, we confirmed a key role for the functional PTPN22 rs2476601 variant and proposed other putative risk loci for GCA involved in Th1, Th17, and Treg cell function