Long-distance movement of phosphate starvation-responsive microRNAs in Arabidopsis.

Plant microRNAs are small RNAs that are important for genetic regulation of processes such as plant development or environmental responses. Specific microRNAs accumulate in the phloem during phosphate starvation, and may act as long-distance signalling molecules. We performed quantitative PCR on Arabidopsis hypocotyl micrograft tissues of wild-type and hen1-6 mutants to assess the mobility of several phosphate starvation-responsive microRNA species. In addition to the previously confirmed mobile species miR399d, the corresponding microRNA* (miR399d*) was identified for the first time as mobile between shoots and roots. Translocation by phosphate-responsive microRNAs miR827 and miR2111a between shoots and roots during phosphate starvation was evident, while their respective microRNA*s were not mobile. The results suggest that long-distance mobility of microRNA species is selective and can occur without the corresponding duplex strand. Movement of miR399d* and root-localised accumulation of miR2111a* opens the potential for persisting microRNA*s to be mobile and functional in novel pathways during phosphate starvation responses.

Prognostic significance of FLT3 mutational status and expression levels in MLL-AF4+ and MLL-germline acute lymphoblastic leukemia.

There is barely any information about the prognostic significance of FLT3 expression and mutational status in cytogenetically distinct subgroups of acute lymphoblastic leukemia (ALL). We analyzed the presence of FLT3-tyrosine kinase domain (TKD) and FLT3-internal tandem duplication (ITD) mutations as well as FLT3 expression levels in 54 newly diagnosed patients with B-ALL (n=49) or T-ALL (n=5). All B/T-ALL samples tested negative for the presence of FLT3-TKD or FLT3-ITD. None of the T-ALL and E2A-PBX1+ B-ALL overexpressed FLT3. In contrast, mainly MLL-AF4+ B-ALL but also ETV6-RUNX1+, BCR-ABL+ or B-ALL displaying normal cytogenetics exhibited significantly higher FLT3 expression levels than normal bone marrow, supporting that aberrantly increased transcription of FLT3, rather than activating FLT3 mutations, contributes to the pathogenesis of these B-ALL. Using the median FLT3 expression as cut-off value we found that high-level FLT3 expression is associated with an extremely poor 1-year overall survival (OS; 0 vs 71%; P=0.002) and disease-free survival (DFS; 0 vs 43%; P=0.03) in MLL-AF4+ B-ALL but not in MLL-germline B-ALL. Cox regression analysis with OS/DFS as end points showed that age>14 years and high-level FLT3 expression were independent prognostic factors when all ALL patients were analyzed together. Importantly, when the MLL-AF4+ B-ALL subgroup was analyzed separately, high-level FLT3 expression was the only independent prognostic factor for OS and treatment outcome. These findings indicate that high FLT3 expression identifies MLL-AF4+ ALL patients at very high risk of treatment failure and poor survival, emphasizing the value of ongoing/future clinical trials for FLT3 inhibitors.

[Implementation and evaluation of case management in Catalonia: the ISP-SMD program]. / La implementación y evaluación del modelo de gestión de casos (case management) en Cataluña: el programa PSI-TMS.

INTRODUCTION: The pilot study of the Individualized Service Program for people with Severe Mental Disorders (ISP-SMD) consists of the implementation of case management services in Catalonia. METHODOLOGY: The ISP-SMD has been implemented in two health care sectors and will be expanded to the rest of Catalonia in the next years. The program serves people with persistent mental disorders who have serious social or family problems and/or who have inadequate mental health service use (high use of inpatient services, no use of community services). The ISP-SMD is a community intervention program that focuses its activities on direct care and coordination between services. Thirty patients have been included in the evaluation. RESULTS: The results of the pilot study have shown that, compared to the year before entering the program, the patients show better clinical status, they decrease their unmet need level, they have more appropriate use of health services and have lower treatment costs. Satisfaction of the patients, family members and professionals with the program is very high. CONCLUSION: It is possible to adapt and implement case management services in Catalonia. When implemented, they improve patient quality of life.

La implantación y evaluación del modelo de gestión de casos (case management) en Cataluña: el programa PSI-TMS / Implementation and evaluation of case management in Catalonia: The ISP-SMD program

Introducción. La prueba piloto del Programa de servicios individualizados para las personas con trastornos mentales severos (PSI-TMS) constituye la implantación en Cataluña de lo que en otros países se ha llamado 'gestión de casos' (case management).Metodología. El PSI-TMS se ha implantado en dos circuitos asistenciales y se expandirá en los próximos años al resto de Cataluña. El programa va dirigido a las personas con trastornos mentales graves y persistentes que padecen una grave repercusión socio-familiar o una utilización inadecuada de recursos sanitarios. El PSI-TMS es un programa de intervención comunitaria que centra sus actividades en la atención directa y la coordinación entre servicios. Treinta pacientes han sido incluidos en la evaluación inicial. Resultados. La evaluación de la prueba piloto ha mostrado que, respecto a la entrada en el programa, los usuarios presentan un mejor estado clínico, disminuyen sus necesidades no cubiertas, utilizan mejor los recursos sanitarios y presentan unos costes de tratamiento menores. La satisfacción de los usuarios, familiares y profesionales con el programa es muy alta. Conclusiones. Como conclusión afirmamos que la adaptación e implantación del modelo de gestión de casos en Cataluña es posible y efectiva (AU)

[The male factor. I. Testicular function and gametogenesis]. / El factor masculino. I. Función testicular y gametogénesis.

The knowledge and treatment of human reproduction impairments have had an outstanding development during the last 15 years, mainly in topics related with infertility and sterility. Unfortunately in the area of male reproduction development has not been the same and despite the efforts accomplished, progress in the diagnosis and therapeutics of male infertility is limited. The functions of the male gonad are sperm production as well as the synthesis and secretion of steroid hormones, mainly testosterone. The efficient regulation of these functions depends on both the precise pituitary secretion of gonadotropic hormones and the endocrine, paracrine and autocrine responses of the testicular somatic cells to this stimulation. In this review we discuss the main events associated with the spermatogenic process, including the interactions among the testicular somatic cells and some characteristics of the physiological function of the hypothalamus-pituitary-testicle axis, as well as some pathophysiological states related to male infertility due to "pretesticular causes".