The MLH1 c.1852_1853delinsGC (p.K618A) Variant in Colorectal Cancer: Genetic Association Study in 18,723 Individuals

Colorectal cancer is one of the most frequent neoplasms and an important cause of mortality in the developed world. Mendelian syndromes account for about 5% of the total burden of CRC, being Lynch syndrome and familial adenomatous polyposis the most common forms. Lynch syndrome tumors develop mainly as a consequence of defective DNA mismatch repair associated with germline mutations in MLH1, MSH2, MSH6 and PMS2. A significant proportion of variants identified by screening these genes correspond to missense or noncoding changes without a clear pathogenic consequence, and they are designated as "variants of uncertain significance'', being the c.1852_1853delinsGC (p.K618A) variant in the MLH1 gene a clear example. The implication of this variant as a low-penetrance risk variant for CRC was assessed in the present study by performing a case-control study within a large cohort from the COGENT consortium-COST Action BM1206 including 18,723 individuals (8,055 colorectal cancer cases and 10,668 controls) and a case-only genotype-phenotype correlation with several clinical and pathological characteristics restricted to the Epicolon cohort. Our results showed no involvement of this variant as a low-penetrance variant for colorectal cancer genetic susceptibility and no association with any clinical and pathological characteristics including family history for this neoplasm or Lynch syndrome.

Impact of Cyberprogram 2.0 on Different Types of School Violence and Aggressiveness

Some antibullying interventions have shown positive outcomes with regard to reducing violence. The aim of the study was to experimentally assess the effects on school violence and aggressiveness of a program to prevent and reduce cyberbullying. The sample was comprised of a randomly selected sample of 176 adolescents (93 experimental, 83 control), aged 13-15 years. The study used a repeated measures pre-posttest design with a control group. Before and after the program, two assessment instruments were administered: the "Cuestionario de Violencia Escolar-Revisado" (CUVE-R [School Violence Questionnaire- Revised]; Alvarez Garcia et al., 2011) and the "Cuestionario de agresividad premeditada e impulsiva" (CAPI-A [Premeditated and Impulsive Aggressiveness Questionnaire]; Andreu, 2010). The intervention consisted of 19 one-hour sessions carried out during the school term. The program contains 25 activities with the following objectives: (1) to identify and conceptualize bullying/cyberbullying; (2) to analyze the consequences of bullying/cyberbullying, promoting participants' capacity to report such actions when they are discovered; (3) to develop coping strategies to prevent and reduce bullying/cyberbullying; and (4) to achieve other transversal goals, such as developing positive variables (empathy, active listening, social skills, constructive conflict resolution, etc.). The pre-posttest ANCOVAs confirmed that the program stimulated a decrease in: (1) diverse types of school violence teachers' violence toward students (ridiculing or publicly humiliating students in front of the class, etc.); students' physical violence (fights, blows, shoves... aimed at the victim, or at his or her property, etc.); students' verbal violence (using offensive language, cruel, embarrassing, or insulting words... toward classmates and teachers); social exclusion (rejection or exclusion of a person or group, etc.), and violence through Information and Communication Technologies (ICT; violent behaviors by means of electronic instruments such as mobile phones and the Internet); and (2) premeditated and impulsive aggressiveness. Pre-posttest MANCOVA revealed differences between conditions with a medium effect size. This work contributes an efficacious intervention tool for the prevention and reduction of peer violence. The conclusions drawn from this study have interesting implications for educational and clinical intervention.

Phenotype consequences of myophosphorylase dysfunction: insights from the McArdle mouse model

McArdle disease, caused by inherited deficiency of the enzyme muscle glycogen phosphorylase (GP-MM), is arguably the paradigm of exercise intolerance. The recent knock-in (p.R50X/p.R50X) mouse disease model allows an investigation of the phenotypic consequences of muscle glycogen unavailability and the physiopathology of exercise intolerance. We analysed, in 2-month-old mice [wild-type (wt/wt), heterozygous (p.R50X/wt) and p.R50X/p.R50X)], maximal endurance exercise capacity and the molecular consequences of an absence of GP-MM in the main glycogen metabolism regulatory enzymes: glycogen synthase, glycogen branching enzyme and glycogen debranching enzyme, as well as glycogen content in slow-twitch (soleus), intermediate (gastrocnemius) and glycolytic/fast-twitch (extensor digitorum longus; EDL) muscles.

Taking advantage of an old concept, "illegitimate transcription", for a proposed novel method of genetic diagnosis of McArdle disease

McArdle disease is a metabolic disorder caused by pathogenic mutations in the PYGM gene. Timely diagnosis can sometimes be difficult with direct genomic analysis, which requires additional studies of cDNA from muscle transcripts. Although the "nonsense-mediated mRNA decay" (NMD) eliminates tissue-specific aberrant transcripts, there is some residual transcription of tissue-specific genes in virtually all cells, such as peripheral blood mononuclear cells (PBMCs).We studied a subset of the main types of PYGM mutations (deletions, missense, nonsense, silent, or splicing mutations) in cDNA from easily accessible cells (PBMCs) in 12 McArdle patients.Analysis of cDNA from PBMCs allowed detection of all mutations. Importantly, the effects of mutations with unknown pathogenicity (silent and splicing mutations) were characterized in PBMCs. Because the NMD mechanism does not seem to operate in nonspecific cells, PBMCs were more suitable than muscle biopsies for detecting the pathogenicity of some PYGM mutations, notably the silent mutation c.645G>A (p.K215=), whose effect in the splicing of intron 6 was unnoticed in previous muscle transcriptomic studies.We propose considering the use of PBMCs for detecting mutations that are thought to cause McArdle disease, particularly for studying their actual pathogenicity.

Muscle signaling in exercise intolerance: Insights from the McArdle mouse model

We recently generated a knock-in mouse model (PYGM p.R50X/p.R50X) of McArdle disease (myophosphorylase deficiency). One mechanistic approach to unveil the molecular alterations caused by myophosphorylase deficiency, which is arguably the paradigm of 'exercise intolerance', is to compare the skeletal-muscle tissue of McArdle, heterozygous, and healthy (wild type (wt)) mice. We analyzed in quadriceps muscle of p.R50X/p.R50X (n=4), p.R50X/wt (n=6) and wt/wt mice (n=5) (all male, 8 wk-old) molecular markers of energy-sensing pathways, oxidative phosphorylation (OXPHOS) and autophagy/proteasome systems, oxidative damage and sarcoplamic reticulum (SR) Ca handling. We found a significant group effect for total AMPK (tAMPK) and ratio of phosphorylated (pAMPK)/tAMPK (P=0.012 and 0.033), with higher mean values in p.R50X/p.R50X mice vs. the other two groups. The absence of massive accumulation of ubiquitinated proteins, autophagosomes or lysosomes in p.R50X/p.R50X mice suggested no major alterations in autophagy/proteasome systems. Citrate synthase activity was lower in p.R50X/p.R50X mice vs. the other two groups (P=0.036) but no statistical effect existed for respiratory chain complexes. We found higher levels of 4-hydroxy-2-nonenal-modified proteins in p.R50X/p.R50X and p.R50X/wt mice compared with the wt/wt group (P=0.011). Sarco(endo)plasmic reticulum ATPase 1 (SERCA1) levels detected at 110kDa tended to be higher in p.R50X/p.R50X and p.R50X/wt mice compared with wt/wt animals (P=0.076), but their enzyme activity was normal. We also found an accumulation of phosphorylated SERCA1 in p.R50X/p.R50X animals. Myophosphorylase deficiency causes alterations in sensory energetic pathways together with some evidence of oxidative damage and alterations in Ca handling but with no major alterations in OXPHOS capacity or autophagy/ubiquitination pathways, which suggests that the muscle tissue of patients is likely to adapt overall favorably to exercise training interventions.

First report of "Cotoneaster pannosus" Franch. ("Rosaceae") in Tarragona Province, and updated distribution area in Spain

Cotoneaster pannosus (Rosaceae), an ornamental shrub native to China, is reported for the first time in Tarragona Province (Catalonia, Spain). Data on demography and accompanying species for the new locality are provided, in addition to a chrorological update at nation level.

¿Barreras invisibles? Actitudes de los estudiantes universitarios ante sus compañeros con discapacidad

El presente trabajo analiza los conocimientos, opiniones y actitudes de los estudiantes universitarios sobre sus compañeros con discapacidad. La integración educativa y social de estos estudiantes es objeto de preocupación y estudio en todo el sistema educativo español, incluida la enseñanza superior en la que 21.942 universitarios con discapacidad se encontraban matriculados en el curso 2013-2014. El estudio se realiza en el marco de dos Proyectos de Innovación Educativa[1] de la Universidad de Málaga en los que se examinaron las actitudes del personal docente e investigador, el alumnado en general y el alumnado con discapacidad de esta institución. En este artículo se recogen las perspectivas de los estudiantes sin discapacidad, necesarias para medir el grado de aceptación dentro de las aulas universitarias. Se empleó una encuesta suministrada mediante correo electrónico a la totalidad de la población de estudiantes de la Universidad de Málaga (N= 32.464). El tamaño de la muestra fue de 620 estudiantes, por lo que trabajamos con un margen de error del 3,9% para la estimación de los porcentajes con un nivel de confianza del 95%. Los datos, analizados mediante análisis estadístico, visibilizan la importancia de un elevado grado de información y conocimiento así como de una experiencia directa con la discapacidad. Ambas circunstancias se traducen en actitudes más positivas y favorables. Tan solo el 20% de los alumnos manifestó haber recibido en alguna ocasión cualquier tipo de información sobre este asunto por parte de la Universidad; no obstante, la mayoría valora positivamente la presencia de alumnos con discapacidad en la Universidad, la posibilidad de contar ellos como compañeros de clase y el enriquecimiento que supone esta convivencia dentro del aula. Se discuten posibles acciones para mejorar las actitudes hacia los estudiantes con discapacidad. Además, se plantea incluir una perspectiva que promueva el empoderamiento de estos estudiantes. [1] PIE 10-135 y PIE 13-103.

Periferias urbanas: retrato del extrarradio barcelonés en las novelas de Javier Pérez Andújar

Javier Pérez Andújar, a través de su propia memoria, crea en Los príncipes valientes (2007) y Paseos con mi madre (2011) un retrato detallado del extrarradio barcelonés. En ambas novelas, el autor combina diferentes elementos: la memoria oral, la metaliteratura, la crónica y la cultura popular. De este modo narra la historia de tres generaciones ubicadas en las afueras de la ciudad. El presente artículo centra su análisis, basándose en una contextualización histórica, en la configuración del espacio y el estudio de las características morfológicas y sociales propias de los extrarradios. Con ello se pretende demostrar la significación histórica y social del extrarradio en la historia contemporánea de Barcelona.

Efficacy of cecropin A-melittin peptides on a sepsis model of infection by pan-resistant Acinetobacter baumannii

Pan-resistant Acinetobacter baumannii have prompted the search for therapeutic alternatives. We evaluate the efficacy of four cecropin A-melittin hybrid peptides (CA-M) in vivo. Toxicity was determined in mouse erythrocytes and in mice (lethal dose parameters were LD(0), LD(50), LD(100)). Protective dose 50 (PD(50)) was determined by inoculating groups of ten mice with the minimal lethal dose of A. baumannii (BMLD) and treating with doses of each CA-M from 0.5 mg/kg to LD(0). The activity of CA-Ms against A. baumannii was assessed in a peritoneal sepsis model. Mice were sacrificed at 0 and 1, 3, 5, and 7-h post-treatment. Spleen and peritoneal fluid bacterial concentrations were measured. CA(1-8)M(1-18) was the less haemolytic on mouse erythrocytes. LD(0) (mg/kg) was 32 for CA(1-8)M(1-18), CA(1-7)M(2-9), and Oct-CA(1-7)M(2-9), and 16 for CA(1-7)M(5-9). PD(50) was not achieved with non-toxic doses (= LD(0)). In the sepsis model, all CA-Ms were bacteriostatic in spleen, and decreased bacterial concentration (p <0.05) in peritoneal fluid, at 1-h post-treatment; at later times, bacterial regrowth was observed in peritoneal fluid. CA-Ms showed local short-term efficacy in the peritoneal sepsis model caused by pan-resistant Acinetobacter baumannii.

Old World megadroughts and pluvials during the Common Era

Climate model projections suggestwidespread drying in the Mediterranean Basin and wetting in Fennoscandia in the coming decades largely as a consequence of greenhouse gas forcing of climate. To place these and other “Old World” climate projections into historical perspective based on more complete estimates of natural hydroclimatic variability, we have developed the “Old World Drought Atlas” (OWDA), a set of year-to-year maps of tree-ring reconstructed summer wetness and dryness over Europe and the Mediterranean Basin during the Common Era.
The OWDA matches historical accounts of severe drought and wetness with a spatial completeness not previously available. In addition, megadroughts reconstructed over north-central Europe in the 11th and mid-15th centuries
reinforce other evidence from North America and Asia that droughts were more severe, extensive, and prolonged over Northern Hemisphere land areas before the 20th century, with an inadequate understanding of their causes. The OWDA provides new data to determine the causes of Old World drought and wetness and attribute past climate variability to forced and/or internal variability.

Prevalência da C.trachomatis entre homens que fazem sexo com homens (HSH) que frequentam um centro clínico comunitário alternativo em Barcelona

RESUMO - Enquadramento: A infeção por Chlamydia trachomatis (CT) é considerada um grave problema de Saúde Pública. É causa de infeções sintomáticas tanto no homem como na mulher, bem como, de infeções assintomáticas que podem ter consequências muito graves a longo prazo. A presença de CT sem tratamento aumenta o risco de transmissão do vírus da imunodeficiência humana. Existem vários estudos publicados de prevalência da CT por todo o mundo, no entanto, estudos de prevalência da CT em populações assintomáticas, envolvendo homens que fazem sexo com homens (HSH) são raros na Europa. Assim, o presente estudo, ao estimar a prevalência e ao descrever as caraterísticas epidemiológicas e de conduta dos HSH, pretende contribuir para o plano de ação contra as IST´s e VIH na Catalunha, através de estratégias concretas para deteção e prevenção da CT. Métodos: Trata-se de um estudo observacional, transversal de prevalência da CT em HSH utentes de um serviço comunitário em Barcelona, com recurso a técnicas de diagnóstico de biologia molecular e a um questionário. Durante Março e Junho de 2015, foram recrutados 200 voluntários de um serviço comunitário em Barcelona que foram testados para CT e NG em três locais anatómicos através de uma PCR em tempo real utilizando o ensaio Anyplex™ CT/NG Real-time Detection. Resultados: O presente estudo permitiu uma caraterização da situação atual quanto á prevalência e aos fatores de risco associados á infeção por CT em HSH. A prevalência nesta população específica foi de 12,6% e os fatores risco associados foram o facto de serem VIH e praticarem sexo anal insertivo/recetivo com parceiro estável. Conclusões: Os resultados obtidos reforçam a necessidade do desenvolvimento de estratégias adequadas de controlo e prevenção da CT nesta população de risco, tais como: rastreios frequentes e tratamento dos casos positivos para quebrar a cadeia de transmissão, promoção da saúde, educação e notificação dos parceiros sexuais. Também demonstram a importância destes rastreios nos três locais anatómicos: uretra, reto e faringe.

Programa los valores en la literatura : manual para tutores.

Contiene una selección de materiales didácticos y de recursos audiovisuales de apoyo

Documentos del XIII Simposio sobre ense??anza de la geolog??a : Alicante del 5 al 10 de julio de 2004

Incluye el libro de salidas de campo: Geolog??a de Alicante

Itinerarios geológicos por la provincia de Alicante para su utilización en Bachillerato.

Esta guía contiene trece itinerarios geológicos situados en la provincia de Alicante. Han participado 55 profesores en un curso organizado por el ICE de la Universidad. Los itinerarios son una propuesta para realizar actividades de campo como herramientas esenciales para mostrar al alumnado las vinculaciones entre la geología y el entorno y éste con el medio dominante. El libro muestra la riqueza del patrimonio geológico de esta provincia.

I Jornadas de Bibliotecas Escolares de Asturias

Resumen basado en la publicaci??n