Novel soluble HLA-A2/MELAN-A complexes selectively stain a differentiation defective subpopulation of CD8+ T cells in patients with melanoma.

Multimeric MHC I-peptide complexes containing phycoerythrin-streptavidin are widely used to detect and investigate antigen-specific CD8+ (and CD4+) T cells. Because such reagents are heterogeneous, we compared their binding characteristics with those of monodisperse dimeric, tetrameric and octameric complexes containing linkers of variable length and flexibility on Melan-A-specific CD8+ T cell clones and peripheral blood mononuclear cells (PBMC) from HLA-A*0201(+) melanoma patients. Striking binding differences were observed for different defined A2/Melan-A(26-35) complexes on T cells depending on their differentiation stage. In particular, short dimeric but not octameric A2/Melan-A(26-35) complexes selectively and avidly stained incompletely differentiated effector-memory T cells clones and populations expressing CD27 and CD28 and low levels of cytolytic mediators (granzymes and perforin). This subpopulation was found in PBMC from all six melanoma patients analyzed and proliferated on peptide stimulation with only modest phenotypic changes. By contrast influenza matrix(58-66) -specific CD8+ PBMC from nine HLA-A*0201(+) healthy donors were efficiently stained by A2/Flu matrix(58-61) multimers, but not dimer and upon peptide stimulation proliferated and differentiated from memory into effector T cells. Thus PBMC from melanoma patients contain a differentiation defective sub-population of Melan-A-specific CD8+ T cells that can be selectively and efficiently stained by short dimeric A2/Melan- A(26-35) complexes, which makes them directly accessible for longitudinal monitoring and further investigation.

IL-12 controls cytotoxicity of a novel subset of self-antigen-specific human CD28+ cytolytic T cells.

Activated CD8 T cells develop cytotoxicity against autologous cells bearing foreign Ags and self/tumor Ags. However, self-specific cytolysis needs to be kept under control to avoid overwhelming immunopathology. After peptide vaccination of melanoma patients, we studied molecular and functional properties of T cell subsets specific for the self/tumor Ag Melan-A/MART-1. Ex vivo analysis revealed three Ag-specific effector memory (EM) populations, as follows: CD28-negative EM (EM28(-)) T cells strongly expressing granzyme/perforin, and two EM28(+) subsets, one with high and the other with low level expression of these cytotoxic proteins. For further functional characterization, we generated 117 stable CD8 T cell clones by ex vivo flow cytometry-based sorting of these subsets. All EM28(-)-derived clones lysed target cells with high efficacy. In contrast, EM28(+)-derived clones were heterogenous, and could be classified in two groups, one with high and the other with low killing capacity, correlating with granzyme/perforin expression. High and low killer phenotypes remained surprisingly stable for several months. However, strongly increased granzyme expression and cytotoxicity were observed after exposure to IL-12. Thus, the data reveal a newly identified subset of CD28(+) conditional killer T cells. Because CD28 can mediate strong costimulatory signals, tight cytotoxicity control, as shown in this study through IL-12, may be particularly important for subsets of T cells expressing CD28.

Com conduir sessions de lectura fàcil : directrius d'organització, planificació i dinamització dels clubs de lectura fàcil

Aquest treball pretén millorar la comprensió lectora dels assistents als clubs de Lectura Fàcil existents a Catalunya a través de la presentació d'una guia de conducció de clubs que presenta un model d'estratègies a seguir en les sessions de lectura. Aquestes orientacions seran útils als conductors novells que no són ni especialistes en didàctica de la llengua ni en literatura i que necessiten resoldre els dubtes de dinamització lectora en els col·lectius amb dificultats lectores. Les estratègies d'aprenentatge proposades provenen de la teoria constructivista en educació que aposta per una actitud molt més activa del lector i aprenent adult d'una L2. De la valoració organitzativa i estratègica de les sessions d'alguns dels clubs i, més concretament, de la tasca duta a terme durant tres anys al Club de Lectura Fàcil de la Biblioteca Mestre Martí Tauler de Rubí, del "com es llegeix" i del si "es comprèn allò llegit", sorgeix la necessitat que el conductor planifiqui acuradament les sessions de treball atenent uns objectius de lectura i el treball d'unes habilitats lectores concretes. Així, doncs, en aquest treball s'ofereixen algunes eines per a la planificació d'aquestes sessions de lectura.

Intervenció psicopedagògica a Primària per millorar l'aprenentatge del càlcul mental a Cicle Mitjà

Es tracta d'un programa d'assessorament i intervenció psicopedagògica en una escola per a treballar el càlcul mental a primària, concretament al cicle mitjà, però també extensible a altres cicles, a partir de l'adaptació de diferents jocs de taula mitjançant la creació de tallers de matemàtiques i amb una pràctica basada en el constructivisme.

Anti-inflammatory and anti-nociceptive effects of Zeyheria montana (Bignoniaceae) ethanol extract

In this work, the analgesic and anti-inflammatory activities of Zeyheria montana Mart. ethanol leaf extract were investigated at doses of 75, 150 and 300 mg/kg body weight. In the analgesic assay, against a chemical stimulus in mice, acetic acid-induced writhes were significantly inhibited by the extract at doses of 75 mg/kg (67.27%), 150 mg/kg (49.38%) and 300 mg/kg (82.87%). Also, a vigorous decrease in hyperalgesia was observed when measured after 2 h and 6 h of lipopolysaccharide stimulation of rats for all doses of extract tested. Z. montana extract, at doses of 75 and 300 mg/kg, caused very slight central analgesia in rats submitted to thermal stimulus, particularly noticeable at 30 min following treatment. The anti-inflammatory activity of Z. montana extract on carrageenan-induced oedema in rats was evaluated. The oedema development, measured at 180 min following carrageenan intraplantar injection, was significantly reduced by all tested doses: 75 mg/kg (33.30%), 150 mg/kg (45.80%) and 300 mg/kg (75.00%). The LD50 value was greater than 2000 mg/kg. These results demonstrated that the ethanol extract from Z. montana leaf possesses anti-nociceptive and anti-inflammatory activities, which could be of relevance for the pharmacological control of pain and inflammatory processes.

DinaWEB : l'organització de recursos accessibles en línia a la Biblioteca Virtual de la Universitat Oberta de Catalunya

El DinaWEB (Dinàmic WEB), és una base de dades desenvolupada per la Universitat Oberta de Catalunya, que té com a objectiu organitzar la informació i els recursos disponibles a la Biblioteca Virtual de la UOC de forma àgil per els usuaris i que permet a l'administrador l'actualització i modificació d'aquests recursos de forma més amigable que fins l'actualitat. La seva funció és substituir les pàgines estàtiques de la intranet de la Biblioteca Virtual de la UOC, per pàgines dinàmiques, generades automàticament per aquesta base de dades.

Clinical pharmacogenomic testing of KRAS, BRAF and EGFR mutations by high resolution melting analysis and ultra-deep pyrosequencing

BACKGROUND: Epidermal growth factor receptor (EGFR) and its downstream factors KRAS and BRAF are mutated in several types of cancer, affecting the clinical response to EGFR inhibitors. Mutations in the EGFR kinase domain predict sensitivity to the tyrosine kinase inhibitors gefitinib and erlotinib in lung adenocarcinoma, while activating point mutations in KRAS and BRAF confer resistance to the anti-EGFR monoclonal antibody cetuximab in colorectal cancer. The development of new generation methods for systematic mutation screening of these genes will allow more appropriate therapeutic choices. METHODS: We describe a high resolution melting (HRM) assay for mutation detection in EGFR exons 19-21, KRAS codon 12/13 and BRAF V600 using formalin-fixed paraffin-embedded samples. Somatic variation of KRAS exon 2 was also analysed by massively parallel pyrosequencing of amplicons with the GS Junior 454 platform. RESULTS: We tested 120 routine diagnostic specimens from patients with colorectal or lung cancer. Mutations in KRAS, BRAF and EGFR were observed in 41.9%, 13.0% and 11.1% of the overall samples, respectively, being mutually exclusive. For KRAS, six types of substitutions were detected (17 G12D, 9 G13D, 7 G12C, 2 G12A, 2 G12V, 2 G12S), while V600E accounted for all the BRAF activating mutations. Regarding EGFR, two cases showed exon 19 deletions (delE746-A750 and delE746-T751insA) and another two substitutions in exon 21 (one showed L858R with the resistance mutation T590M in exon 20, and the other had P848L mutation). Consistent with earlier reports, our results show that KRAS and BRAF mutation frequencies in colorectal cancer were 44.3% and 13.0%, respectively, while EGFR mutations were detected in 11.1% of the lung cancer specimens. Ultra-deep amplicon pyrosequencing successfully validated the HRM results and allowed detection and quantitation of KRAS somatic mutations. CONCLUSIONS: HRM is a rapid and sensitive method for moderate-throughput cost-effective screening of oncogene mutations in clinical samples. Rather than Sanger sequence validation, next-generation sequencing technology results in more accurate quantitative results in somatic variation and can be achieved at a higher throughput scale.

Alternancia de códigos en la expresión del caso partitivo

En esta comunicación pretendemos aportar evidencias empíricas a favor de la estructurade los nominales propuesta por Martí (1994: 94). De acuerdo con este análisis los nominales indefinidos son cuantificadores SQ que seleccionan una proyección funcional de caso partitivo (encabezada en español por de)

Nosocomial bacteremia due to an as yet unclassified acinetobacter genomic species 17-like strain.

We describe a case of bacteremia due to an as yet unclassified Acinetobacter genomic species 17-like strain. The recognition of this microorganism as non-Acinetobacter baumannii may have important epidemiological implications, as it relieves the hospital of the implementation of barrier precautions for patients infected or colonized as may be necessary with a multiresistant A. baumannii epidemic.

Ordre de mots i estructura informativa a la llengua de Francesc Eiximenis

En aquest estudi s’examina la llengua d’alguns textos de Francesc Eiximenis (concretament, el ‘Dotzè del Crestià’ i les cartes autògrafes publicades per Martí 2002) per tal d’aprofundir en la distribució de l’estructura informativa i el consegüent ordre de mots que utilitza l’autor. L’objectiu d’aquesta comunicació és aprofundir en els casos d’ avantposició del català antic que correspon a una estructura de focalització feble (no contrastiva)

Psychometric characteristics of the Spanish version of instruments to measure neck pain disability

BACKGROUND. The NDI, COM and NPQ are evaluation instruments for disability due to NP. There was no Spanish version of NDI or COM for which psychometric characteristics were known. The objectives of this study were to translate and culturally adapt the Spanish version of the Neck Disability Index Questionnaire (NDI), and the Core Outcome Measure (COM), to validate its use in Spanish speaking patients with non-specific neck pain (NP), and to compare their psychometric characteristics with those of the Spanish version of the Northwick Pain Questionnaire (NPQ). METHODS. Translation/re-translation of the English versions of the NDI and the COM was done blindly and independently by a multidisciplinary team. The study was done in 9 primary care Centers and 12 specialty services from 9 regions in Spain, with 221 acute, subacute and chronic patients who visited their physician for NP: 54 in the pilot phase and 167 in the validation phase. Neck pain (VAS), referred pain (VAS), disability (NDI, COM and NPQ), catastrophizing (CSQ) and quality of life (SF-12) were measured on their first visit and 14 days later. Patients' self-assessment was used as the external criterion for pain and disability. In the pilot phase, patients' understanding of each item in the NDI and COM was assessed, and on day 1 test-retest reliability was estimated by giving a second NDI and COM in which the name of the questionnaires and the order of the items had been changed. RESULTS. Comprehensibility of NDI and COM were good. Minutes needed to fill out the questionnaires [median, (P25, P75)]: NDI. 4 (2.2, 10.0), COM: 2.1 (1.0, 4.9). Reliability: [ICC, (95%CI)]: NDI: 0.88 (0.80, 0.93). COM: 0.85 (0.75,0.91). Sensitivity to change: Effect size for patients having worsened, not changed and improved between days 1 and 15, according to the external criterion for disability: NDI: -0.24, 0.15, 0.66; NPQ: -0.14, 0.06, 0.67; COM: 0.05, 0.19, 0.92. Validity: Results of NDI, NPQ and COM were consistent with the external criterion for disability, whereas only those from NDI were consistent with the one for pain. Correlations with VAS, CSQ and SF-12 were similar for NDI and NPQ (absolute values between 0.36 and 0.50 on day 1, between 0.38 and 0.70 on day 15), and slightly lower for COM (between 0.36 and 0.48 on day 1, and between 0.33 and 0.61 on day 15). Correlation between NDI and NPQ: r = 0.84 on day 1, r = 0.91 on day 15. Correlation between COM and NPQ: r = 0.63 on day 1, r = 0.71 on day 15. CONCLUSION. Although most psychometric characteristics of NDI, NPQ and COM are similar, those from the latter one are worse and its use may lead to patients' evolution seeming more positive than it actually is. NDI seems to be the best instrument for measuring NP-related disability, since its results are the most consistent with patient's assessment of their own clinical status and evolution. It takes two more minutes to answer the NDI than to answer the COM, but it can be reliably filled out by the patient without assistance. TRIAL REGISTRATION Clinical Trials Register NCT00349544.

Aproximació a l'evolució del paisatge vegetal a les comarques de la Selva i del Vallès

L'objectiu d'aquest article és presentar les línies bàsiques de l'evolució del paisatge vegetal d'una part d'una àrea geogràfica que des de l'antiguitat ha estat un passadís històric d'assentaments i comunicacions i que comprèn les comarques de la Selva, del Vallès Oriental i del Vallès Occidental Biogeogràficament es tracta d'una zona de contacte entre el món mediterrani, representat a nivell climàtic per l'alzinar litoral, i l'eurosiberià, que té com a principals comunitats climàtiques la roureda de roure martinenc i la fageda amb el·lèbor verd

Viatge al Marroc de la Secció de Geografia de la Universitat de Girona, 24-30 d'abril de 2000

A group of teachers and students of the Geography Unit of the University of Girona conducted a field trip in a part of Northern Morocco, which once belonged to the Spanish Protectorate. The visit took place between 24th and 30th April 2000. Some teachers of the University of Tetouan accompanied the group and offered comprehensive geographical explanations of the area, including physical, social and economic aspects

Estudio transversal sobre la prevalencia de la Enfermedad Metabólica Ósea (EMO) y Nutrición Parenteral Domiciliaria (NPD) en España: datos del Grupo NADYA

Patients with intestinal failure who receive HPN are at high risk of developing MBD. The origin of this bone alteration is multifactorial and depends greatly on the underlying disease for which the nutritional support is required. Data on the prevalence of this disease in our environment is lacking, so NADYA-SEMPE group has sponsored this transversal study with the aim of knowing the actual MBD prevalence. MATERIAL AND METHODS: Retrospective data from 51 patients from 13 hospitals were collected. The questionnaire included demographic data as well as the most clinically relevant for MBD data. Laboratory data (calciuria, PTH, 25 -OH -vitamin D) and the results from the first and last bone densitometry were also registered. RESULTS: Bone mineral density had only been assessed by densitometry in 21 patients at the moment HPN was started. Bone quality is already altered before HPN in a significant percentage of cases (52%). After a mean follow up of 6 years, this percentage increases up to 81%. Due to retrospective nature of the study and the low number of subjects included it has not been possible to determine the role that HPN plays in MBD etiology. Only 35% of patients have vitamin D levels above the recommended limits and the majority of them is not on specific supplementation. CONCLUSIONS: HPN is associated with very high risk of MBD, therefore, management protocols that can lead to early detection of the problem as well as guiding for follow up and treatment of these patients are needed.

Els Atles comarcals de Catalunya: un producte innovador per a uns continguts tradicionals

La present comunicació pretén ressenyar l’aportació dels Atles comarcals de Catalunya al coneixement del nostre territori com una obra no només de caire acadèmic sinó també divulgatiu i aplicat. En primer lloc, es constata la filiació de l’obra al llegat de la geografia clàssica catalana i a les aportacions tradicionals —monografies i les obres generals― que han disseccionat el país des de l’òptica comarcal. En segon lloc, es detalla el seu procés de concepció i elaboració. Finalment, es destaquen les innovacions que el nou format CD-Rom i les possibilitats d’interacció cartogràfica amb servidors externs suposen en el sentit d’innovació respecte de les aportacions anteriors