Bedeutung der Arbeitsallianz in der Psychotherapie

Das pantheoretische Konzept der Arbeitsallianz stellt die kollaborative Qualität der an der Therapie beteiligten Personen (i. e. zumeist der Patient und der Therapeut) in den Mittelpunkt. Die Arbeitsallianz ist die weltweit am besten untersuchte Prozessvariable in der Psychotherapie. Die vorliegende Arbeit bietet einen Überblick über den aktuellen metaanalytischen Wissensstand. Basierend auf 200 Primärstudien mit 14.000 teilnehmenden Patienten wurde der Zusammenhang zwischen Arbeitsallianz und Therapieerfolg metaanalytisch untersucht. Die Arbeitsallianz erweist sich als äußerst robuster Prädiktor, der moderate 8 % der Varianz des Therapieerfolgs erklärt. Der Zusammenhang über die verschiedenen Psychotherapietraditionen hinweg zeigte sich sowohl unter randomisierten kontrollierten, manualisierten Studienbedingungen als auch unter naturalistischen Voraussetzungen. Der Effekt fand sich zudem in den störungsspezifischen Erfolgseinschätzungen und den generelleren Erfolgsmaßen. Die moderaten Therapeuteneffekte in den Primärstudien konnten metaanalytisch bestätigt werden. Soziokulturelle Aspekte wie Substanzmissbrauch und ethnische Minoritäten moderieren den Einfluss zwischen Arbeitsallianz und Therapieerfolg. Die Nähe der Forscher zum Allianzkonzept („allegiance“) beeinflusst die Vorhersagekraft der frühen Allianz zwar statistisch bedeutsam, jedoch nicht substanziell.

The transcriptome of equine peripheral blood mononuclear cells.

Complete transcriptomic data at high resolution are available only for a few model organisms with medical importance. The gene structures of non-model organisms are mostly computationally predicted based on comparative genomics with other species. As a result, more than half of the horse gene models are known only by projection. Experimental data supporting these gene models are scarce. Moreover, most of the annotated equine genes are single-transcript genes. Utilizing RNA sequencing (RNA-seq) the experimental validation of predicted transcriptomes has become accessible at reasonable costs. To improve the horse genome annotation we performed RNA-seq on 561 samples of peripheral blood mononuclear cells (PBMCs) derived from 85 Warmblood horses. The mapped sequencing reads were used to build a new transcriptome assembly. The new assembly revealed many alternative isoforms associated to known genes or to those predicted by the Ensembl and/or Gnomon pipelines. We also identified 7,531 transcripts not associated with any horse gene annotated in public databases. Of these, 3,280 transcripts did not have a homologous match to any sequence deposited in the NCBI EST database suggesting horse specificity. The unknown transcripts were categorized as coding and noncoding based on predicted coding potential scores. Among them 230 transcripts had high coding potential score, at least 2 exons, and an open reading frame of at least 300 nt. We experimentally validated 9 new equine coding transcripts using RT-PCR and Sanger sequencing. Our results provide valuable detailed information on many transcripts yet to be annotated in the horse genome.

Insulin, CCAAT/enhancer-binding proteins and lactate regulate the human 11β-hydroxysteroid dehydrogenase type 2 gene expression in colon cancer cell lines.

11β-Hydroxysteroid dehydrogenases (11beta-HSD) modulate mineralocorticoid receptor transactivation by glucocorticoids and regulate access to the glucocorticoid receptor. The isozyme 11beta-HSD2 is selectively expressed in mineralocorticoid target tissues and its activity is reduced in various disease states with abnormal sodium retention and hypertension, including the apparent mineralocorticoid excess. As 50% of patients with essential hypertension are insulin resistant and hyperinsulinemic, we hypothesized that insulin downregulates the 11beta-HSD2 activity. In the present study we show that insulin reduced the 11beta-HSD2 activity in cancer colon cell lines (HCT116, SW620 and HT-29) at the transcriptional level, in a time and dose dependent manner. The downregulation was reversible and required new protein synthesis. Pathway analysis using mRNA profiling revealed that insulin treatment modified the expression of the transcription factor family C/EBPs (CCAAT/enhancer-binding proteins) but also of glycolysis related enzymes. Western blot and real time PCR confirmed an upregulation of C/EBP beta isoforms (LAP and LIP) with a more pronounced increase in the inhibitory isoform LIP. EMSA and reporter gene assays demonstrated the role of C/EBP beta isoforms in HSD11B2 gene expression regulation. In addition, secretion of lactate, a byproduct of glycolysis, was shown to mediate insulin-dependent HSD11B2 downregulation. In summary, we demonstrate that insulin downregulates HSD11B2 through increased LIP expression and augmented lactate secretion. Such mechanisms are of interest and potential significance for sodium reabsorption in the colon.