Patterns and correlates of expressed emotion, perceived criticism, and rearing style in first admitted early-onset schizophrenia spectrum disorders.

The aim of this study was to assess patterns and correlates of family variables in 31 adolescents treated for their first episode of a schizophrenia spectrum disorder (early-onset schizophrenia [EOS]). Expressed emotion, perceived criticism, and rearing style were assessed. Potential correlates were patient psychopathology, premorbid adjustment, illness duration, quality of life (QoL), sociodemographic variables, patient and caregiver "illness concept," and caregiver personality traits and support. Families were rated as critical more frequently by patients than raters (55% vs. 13%). Perceived criticism was associated with worse QoL in relationship with parents and peers. An adverse rearing style was associated with a negative illness concept in patients, particularly with less trust in their physician. Future research should examine perceived criticism as a predictor of relapse and indicator of adolescents with EOS who need extended support and treatment. Rearing style should be carefully observed because of its link with patients' illness concept and, potentially, to service engagement and medication adherence.

Discovery of benzothiazole guanidines as novel inhibitors of thrombin and trypsin IV.

In a project to find novel neutral P1 fragments for the synthesis of thrombin inhibitors with improved pharmacokinetic properties, fragments containing a benzothiazole guanidine scaffold were identified as weak thrombin inhibitors. WaterLOGSY (Water-Ligand Observed via Gradient SpectroscopY) NMR was used to detect fragments binding to thrombin and these fragments were followed up by Biacore A100 affinity measurements and enzyme assays. A crystal structure of the most potent compound with thrombin was obtained and revealed an unexpected binding mode as well as the key interactions of the fragment with the protein. Based on these results, the structure-based design and synthesis of a small series of optimized novel substituted benzothiazole guanidines with comparatively low pK(a) values was accomplished. Testing of these compounds against human trypsin I and human trypsin IV revealed unexpected inhibitory activity and selectivity of some of the compounds, making them attractive starting points for selective trypsin inhibitors.

[Separation of parents: how is it conveyed to children? How does the content of the communication influence the separation experience of children?]. / Trennung der Eltern: Wie wird sie den Kindern vermittelt und welchen Einfluss haben Art und Inhalt der Mitteilung auf das Trennungserleben der Kinder?

On the basis of 45 expert opinions of custody cases involving 89 children dating from 1996-1999 and of 62 questionnaires answered by the parents it was examined, how the parents told their children about the impending separation. We were interested if the way the parents told their children and the contents of the communication had an impact on coping with the separation. We found that only 48.9% of the families talked about the separation. 35.5% of the children were not informed, 12.4% of the children were not told the truth by their parents. There was no clear connection between the way the children were informed and their coping behaviour. Yet it could be shown that talking to the children had a positive effect on the relationship between the father and the child. The discussion of the results will point out the complexity and importance of this topic which has not been sufficiently considered in the literature and by parents planning a divorce. Yet looking at the rising divorce rate one can see how highly topical it is and will remain in the future.

Discovery of the Fibrinolysis Inhibitor AZD6564, Acting via Interference of a Protein-Protein Interaction.

A class of novel oral fibrinolysis inhibitors has been discovered, which are lysine mimetics containing an isoxazolone as a carboxylic acid isostere. As evidenced by X-ray crystallography the inhibitors bind to the lysine binding site in plasmin thus preventing plasmin from binding to fibrin, hence blocking the protein-protein interaction. Optimization of the series, focusing on potency in human buffer and plasma clotlysis assays, permeability, and GABAa selectivity, led to the discovery of AZD6564 (19) displaying an in vitro human plasma clot lysis IC50 of 0.44 µM, no detectable activity against GABAa, and with DMPK properties leading to a predicted dose of 340 mg twice a day oral dosing in humans.