Medial temporal lobe function during emotional memory in early Alzheimer's disease, mild cognitive impairment and healthy ageing:an fMRI study

Background: Relative to intentional memory encoding, which quickly declines in Mild Cognitive Impairment (MCI) and Alzheimer's disease (AD), incidental memory for emotional stimuli appears to deteriorate more slowly. We hypothesised that tests of incidental emotional memory may inform on different aspects of cognitive decline in MCI and AD.Methods: Patients with MCI, AD and Healthy Controls (HC) were asked to attend to emotional pictures (i.e., positive and neutral) sequentially presented during an fMRI session. Attention was monitored behaviourally. A surprise post-scan recognition test was then administered.Results: The groups remained attentive within the scanner. The post-scan recognition pattern was in the form of (HC = MCI) &gt; AD, with only the former group showing a clear benefit from emotional pictures. fMRI analysis of incidental encoding demonstrated clusters of activation in para-hippocampal regions and in the hippocampus in HC and MCI patients but not in AD patients. The pattern of activation observed in MCI patients tended to be greater than that found in HC.Conclusions: The results suggest that incidental emotional memory might offer a suitable platform to investigate, using behavioural and fMRI measures, subtle changes in the process of developing AD. These changes seem to differ from those found using standard episodic memory tests. The underpinnings of such differences and the potential clinical use of this methodology are discussed in depth.</p

Rapid detection of carriers with BRCA1 and BRCA2 mutations using high resolution melting analysis

<p>Abstract</p> <p>Background</p> <p>Germline inactivating mutations in <it>BRCA1 </it>and <it>BRCA2 </it>underlie a major proportion of the inherited predisposition to breast and ovarian cancer. These mutations are usually detected by DNA sequencing. Cost-effective and rapid methods to screen for these mutations would enable the extension of mutation testing to a broader population. High resolution melting (HRM) analysis is a rapid screening methodology with very low false negative rates. We therefore evaluated the use of HRM as a mutation scanning tool using, as a proof of principle, the three recurrent BRCA1 and BRCA2 founder mutations in the Ashkenazi Jewish population in addition to other mutations that occur in the same regions.</p> <p>Methods</p> <p>We designed PCR amplicons for HRM scanning of <it>BRCA1 </it>exons 2 and 20 (carrying the founder mutations185delAG and 5382insC respectively) and the part of the <it>BRCA2 </it>exon 11 carrying the 6174delT founder mutation. The analysis was performed on an HRM-enabled real time PCR machine.</p> <p>Results</p> <p>We tested DNA from the peripheral blood of 29 individuals heterozygous for known mutations. All the Ashkenazi founder mutations were readily identified. Other mutations in each region that were also readily detected included the recently identified Greek founder mutation 5331G>A in exon 20 of <it>BRCA1</it>. Each mutation had a reproducible melting profile.</p> <p>Conclusion</p> <p>HRM is a simple and rapid scanning method for known and unknown <it>BRCA1 </it>and <it>BRCA2 </it>germline mutations that can dramatically reduce the amount of sequencing required and reduce the turnaround time for mutation screening and testing. In some cases, such as tracking mutations through pedigrees, sequencing may only be necessary to confirm positive results. This methodology will allow for the economical screening of founder mutations not only in people of Ashkenazi Jewish ancestry but also in other populations with founder mutations such as Central and Eastern Europeans (<it>BRCA1 </it>5382insC) and Greek Europeans (<it>BRCA1 </it>5331G>A).</p

Analytic philosophy for biomedical research: the imperative of applying yesterday's timeless messages to today's impasses

The mantra that "the best way to predict the future is to invent it" (attributed to the computer scientist Alan Kay) exemplifies some of the expectations from the technical and innovative sides of biomedical research at present. However, for technical advancements to make real impacts both on patient health and genuine scientific understanding, quite a number of lingering challenges facing the entire spectrum from protein biology all the way to randomized controlled trials should start to be overcome. The proposal in this chapter is that philosophy is essential in this process. By reviewing select examples from the history of science and philosophy, disciplines which were indistinguishable until the mid-nineteenth century, I argue that progress toward the many impasses in biomedicine can be achieved by emphasizing theoretical work (in the true sense of the word 'theory') as a vital foundation for experimental biology. Furthermore, a philosophical biology program that could provide a framework for theoretical investigations is outlined