Recommendations for the diagnosis and management of Alzheimer's disease and other disorders associated with dementia: EFNS guideline

The aim of this international guideline on dementia was to present a peer-reviewed evidence-based statement for the guidance of practice for clinical neurologists, geriatricians, psychiatrists, and other specialist physicians responsible for the care of patients with dementia. It covers major aspects of diagnostic evaluation and treatment, with particular emphasis on the type of patient often referred to the specialist physician. The main focus is Alzheimer's disease, but many of the recommendations apply to dementia disorders in general. The task force working group considered and classified evidence from original research reports, meta-analysis, and systematic reviews, published before January 2006. The evidence was classified and consensus recommendations graded according to the EFNS guidance. Where there was a lack of evidence, but clear consensus, good practice points were provided. The recommendations for clinical diagnosis, blood tests, neuroimaging, electroencephalography (EEG), cerebrospinal fluid (CSF) analysis, genetic testing, tissue biopsy, disclosure of diagnosis, treatment of Alzheimer's disease, and counselling and support for caregivers were all revised when compared with the previous EFNS guideline. New recommendations were added for the treatment of vascular dementia, Parkinson's disease dementia, and dementia with Lewy bodies, for monitoring treatment, for treatment of behavioural and psychological symptoms in dementia, and for legal issues. The specialist physician plays an important role together with primary care physicians in the multidisciplinary dementia teams, which have been established throughout Europe. This guideline may contribute to the definition of the role of the specialist physician in providing dementia health care.     

Modulation of intein activity by its neighboring extein substrates

Inteins comprise a large family of phylogenetically widespread self-splicing protein catalysts that colonize diverse host proteins. The evolutionary and functional relationship between the intein and the split-host protein, the exteins, is largely unknown. To probe an association, we developed an in vivo and in vitro intein assay based on FRET. The FRET assay reports cleavage of the intein from its N-terminal extein. Applying this assay to randomized extein libraries, we show that the nature of the extein substrate bordering the intein can profoundly influence intein activity. Residues proximal to the intein-splicing junction in both N- and C-terminal exteins can accelerate the N-terminal cleavage rate by >4-fold or attenuate cleavage by 1,000-fold, both resulting in compromised self-splicing efficiency. The existence and the magnitude of extein effects require consideration for maximizing the utility of inteins in biotechnological applications, and they predict biases in intein integration sites in nature.     

EMS in Mauritius

Mauritius lies in the southwest Indian Ocean about 1250 miles from the African coast and 500 miles from Madagascar. Mauritius (estimated population 1,230,602) became independent from the United Kingdom in 1968 and has one of the highest GDP per capita in Africa.     

The age of second language acquisition determines the variability in activation elicited by narration in three languages in Broca’s and Wernicke’s area

It is generally accepted that the presence of a second language (L2) has an impact on the neuronal substrates build up and used for language processing; the influence of the age of L2 exposure, however, is not established. We tested the hypothesis that the age of L2 acquisition has an effect on the cortical representation of a multilingual repertoire in 44 multilinguals with different age of exposure to a L2 (simultaneous or covert simultaneous exposure to L1 and L2, sequential acquisition of L1 and L2 between 1 and 5 years, late learning of L2 after 9 years of age) and all fluent in a late learned L3. Regional activation in a language production task showed a high in-between-subject variability, which was higher than within-subject variability between L1, L2, and L3. We, therefore, performed a single subject analysis and calculated the within-subject variance in the numbers of activated voxels in Broca’s and Wernicke’s area. Subjects with early exposure to L2 showed low variability in brain activation in all three languages, in the two early as well as the late learned language. In contrast, late multilinguals exhibited higher variability. Thus, cerebral representation of languages is linked to the age of L2 acquisition: early exposure to more than one language gives rise to a language processing network that is activated homogeneously by early and late learned languages, while the inhomogeneous activation in late multilinguals indicates more independent access to the multilingual repertoire. Early passive exposure to L2 results in the same low variance as active bilingual upbringing. Variability in local brain activity increases progressively from the simultaneous to late L2 exposure, indicating a gradual transition from the mode of early bilingual language representation to that of late ones.     

Transient role of the rat prelimbic cortex in goal-directed behaviour

Lesion studies show that goal-directed actions mediated by action-outcome (A-O) associations and habits mediated by stimulus-response (S-R) associations can be dissociated during instrumental training, with the prelimbic region of the medial prefrontal cortex being involved in the former and the infralimbic region in the latter. The present work further investigates the role of the prelimbic region in acquisition vs. expression of goal-directed instrumental behaviour, using reversible neuronal inactivation and outcome devaluation procedures. In a first experiment, inactivating the prelimbic cortex at the time of testing did not alter the sensitivity to devaluation, indicating that this region was not essential for the expression of A-O associations. In a second experiment, the prelimbic cortex was inactivated throughout the training phase. At the time of testing the performance was insensitive to devaluation, indicating that the acquired response was not goal-directed but mediated by an S-R association. These data challenge the view that the habit system replaces the goal-directed system as training progresses. They show that the prelimbic cortex plays a transient but crucial role in the acquisition of goal-directed responding and that the A-O and S-R systems can operate in a competitive fashion early in training.