Brain metabolite composition in relation to cognitive function and dystrophin mutations in boys with Duchenne muscular dystrophy

Duchenne muscular dystrophy (DMD) is a hereditary X-linked recessive disorder affecting the synthesis of dystrophin, a protein essential for structural stability in muscle. Dystrophin also occurs in the central nervous system, particularly in the neocortex, hippocampus and cerebellum. Quantitative metabolic analysis by localized (1) H MRS was performed in the cerebellum (12 patients and 15 controls) and a temporo-parietal location (eight patients and 15 controls) in patients with DMD and healthy controls to investigate possible metabolic differences. In addition, the site of individual mutations on the dystrophin gene was analyzed and neuropsychological cognitive functions were examined. Cognitive deficits in the patient group were found in line with earlier investigations, mainly concerning verbal short-term memory, visuo-spatial long-term memory and verbal fluency, but also the full-scale IQ. Causal mutations were identified in all patients with DMD. Quantitative MRS showed consistent choline deficits, in both cerebellar white matter and temporo-parietal cortex, as well as small, but significant, metabolic abnormalities for glutamate and total N-acetyl compounds in the temporo-parietal region. Compartment water analysis did not reveal any abnormalities. In healthy subjects, choline levels were age related in the cerebellum. The choline deficit contrasts with earlier findings in DMD, where a surplus of choline was postulated for the cerebellum. In patients, total N-acetyl compounds in the temporo-parietal region were related to verbal IQ and verbal short-term memory. However, choline, the putative main metabolic abnormality, was not found to be associated with cognitive deficits. Furthermore, in contrast with the cognitive performance, the metabolic brain composition did not depend significantly on whether or not gene mutations concerned the expression of the dystrophin isoform Dp140, leading to the conclusion that the effect of the missing Dp140 isoform on cognitive performance is not mediated through the observed metabolite composition, or is caused by local effects beyond the resolution accessible to MRS investigations.

What is to be done with surplus embryos? Attitude formation with ambivalence in German fertility patients

Improved pregnancy rates in IVF have led to increasing numbers of surplus embryos which can potentially be used for purposes like donation to another infertile couple or further research. Individuals report high levels of ambivalence concerning the donation of surplus embryos. This study examined which strategies infertile patients use to deal with this ambivalence when asked to evaluate potential dispositions of surplus embryos created during IVF. Guideline-based interviews with fertility patients were audio-recorded and transcribed verbatim. Following the principle of theoretical sampling, eight interviews were analysed by use of Grounded Theory. Analyses focused on processes of individual attitude formation. Strategies for handling ambivalence during attitude formation were identified: the six strategies comprise cognitive and communicative strategies, and were integrated into a model of attitude formation under ambivalence. As ambivalence is a relevant phenomenon in attitude formation within IVF treatment, assessment of ambivalence is strongly recommended in social science studies investigating ethical problems in patient care. In the context of informed consent, there is a need for individual counselling which draws attention to the conflicting values during attitude formation. Counsellors should be aware of the signs of and the strategies to deal with ambivalence.