Antagonism between C/EBPβ and FOG in eosinophil lineage commitment of multipotent hematopoietic progenitors

The commitment of multipotent cells to particular developmental pathways requires specific changes in their transcription factor complement to generate the patterns of gene expression characteristic of specialized cell types. We have studied the role of the GATA cofactor Friend of GATA (FOG) in the differentiation of avian multipotent hematopoietic progenitors. We found that multipotent cells express high levels of FOG mRNA, which were rapidly down-regulated upon their C/EBPβ-mediated commitment to the eosinophil lineage. Expression of FOG in eosinophils led to a loss of eosinophil markers and the acquisition of a multipotent phenotype, and constitutive expression of FOG in multipotent progenitors blocked activation of eosinophil-specific gene expression by C/EBPβ. Our results show that FOG is a repressor of the eosinophil lineage, and that C/EBP-mediated down-regulation of FOG is a critical step in eosinophil lineage commitment. Furthermore, our results indicate that maintenance of a multipotent state in hematopoiesis is achieved through cooperation between FOG and GATA-1. We present a model in which C/EBPβ induces eosinophil differentiation by the coordinate direct activation of eosinophil-specific promoters and the removal of FOG, a promoter of multipotency as well as a repressor of eosinophil gene expression

Identification of target tissue for gene therapy by multi- tracer PET-imaging.

Copyright 2002 by the Society of Nuclear Medicin

High-resolution imaging of gene-expression by positron emission tomography.

Copyright 2002 by the Society of Nuclear Medicin

Cost-effectiveness of tiotropium versus salmeterol: the POET-COPD trial

Hoogendoorn M, Al MJ, Beeh K-M, et al. Cost-effectiveness of tiotropium versus salmeterol: the POET-COPD trial. European Respiratory Journal. 2013;41(3):556-564.The aim of this study was to perform a 1-yr trial-based cost-effectiveness analysis (CEA) of tiotropium versus salmeterol followed by a 5-yr model-based CEA. The within-trial CEA, including 7,250 patients with moderate to very severe chronic obstructive pulmonary disease (COPD), was performed alongside the 1-yr international randomised controlled Prevention of Exacerbations with Tiotropium (POET)-COPD trial comparing tiotropium with salmeterol regarding the effect on exacerbations. Main end-points of the trial-based analysis were costs, number of exacerbations and exacerbation days. The model-based analysis was conducted to extrapolate results to 5 yrs and to calculate quality-adjusted life years (QALYs). 1-yr costs per patient from the German statutory health insurance (SHI) perspective and the societal perspective were 126 (95% uncertainty interval (UI) (sic)55-195) and (sic)170 (95% UI (sic)77-260) higher for tiotropium, respectively. The annual number of exacerbations was 0.064 (95% UI 0.010-0.118) lower for tiotropium, leading to a reduction in exacerbation-related costs of (sic)87 (95% UI (sic)19-157). The incremental cost-effectiveness ratio was 1,961 per exacerbation avoided from the SHI perspective and (sic)2,647 from the societal perspective. In the model-based analyses, the 5-yr costs per QALY were (sic)3,488 from the SHI perspective and (sic)8,141 from the societal perspective. Tiotropium reduced exacerbations and exacerbation-related costs, but increased total costs. Tiotropium can be considered cost-effective as the resulting cost-effectiveness ratios were below commonly accepted willingness-to-pay thresholds

Características biomecânicas, ergonômicas e clínicas da postura sentada: uma revisão

A posição sentada é a mais adotada nos ambientes de trabalho, na escola e nas atividades de lazer. Porém, a manutenção prolongada dessa posição ocasiona a adoção de posturas inadequadas e sobrecarrega as estruturas do sistema musculoesquelético, o que pode acarretar dor e lesão na coluna lombar. A presente revisão teve como objetivo identificar os fatores biomecânicos, ergonômicos e clínicos envolvidos na sustentação da postura sentada. Para isso, foram consultadas as bases de dados ISI Web of Knowledge, Medline, Pubmed e EBSCO Host, sendo selecionados 72 artigos publicados entre 1965 e 2010. Foi possível identificar que na posição sentada não existe uma postura ideal a ser sustentada, mas algumas posturas são mais recomendadas do que outras, tal como a postura sentada ereta e a postura lordótica. As cadeiras influenciam o padrão da posição sentada: conforme seu design, pode permitir maior variedade de posturas. Modificações na cadeira e a utilização de exercícios para o aumento da resistência muscular e da propriocepção, bem como a reeducação postural, são intervenções úteis para reduzir o impacto causado pela posição sentada prolongada no sistema musculoesquelético.The sitting posture is the most adopted in work environment, at school and in leisure activities. However, prolonged maintenance of this position causes the adoption of inadequate postures and overloads skeletal muscle structures, which may lead to spine pain and injuries. The purpose of the present review was to identify biomechanic, ergonomic, and clinical features involved in maintenance of the sitting position. The search in ISI Web of Knowledge, Medline, Pubmed and EBSCOHost data bases led to selecting 72 articles published between 1965 and 2010. Results show that there is not an ideal posture to be kept, but some postures are more recommended than others, like the upright sitting and the lordotic postures. Chairs influence the pattern of sitting, and their design allows for posture diversity. Changes in the chair, exercises to improve endurance and proprioception, as well as postural re-education, are useful interventions to reduce the impact of prolonged sitting position on the skeletal muscle system