Germline mutations in APC tumor suppressor gene are responsible for familial adenomatous polyposis (FAP). A major role of these genetic changes is the constitutive activation of -catenin-Tcf-4 mediated transcription of nuclear target genes, but other cellular functions can be misregulated. To assess how different APC mutations can drive the early steps of colonic tumorigenesis, we studied the effect of 10 different germline-truncating alterations on the phenotype of the corresponding adenomas. A significant reduction of apoptosis, uncoupled with an increased c-myc and cyclin-D1 expression, was seen with a frameshift mutation on codon 1383, in the 20-aa repeats of the -catenin degradation domain, independent of a somatic alteration on the wildtype allele. The decreased apoptotic level was associated with a higher incidence of cancerization. No other APC mutation was linked with a similar effect, even in presence of a somatic allelic loss. These findings suggest that mutations in critical sites of the -catenin degradation domain of APC gene can convey a selective advantage to the colonic neoplastic clones by altering the apoptotic surveillance rather than enhancing the -catenin-Tcf-4 transcription of growth-promoting genes.
Purpose
Music stimulation is considered beneficial for people with advanced Alzheimer’s disease. The purpose of this paper is to assess a tablet-based program to promote music-related hand responses and positive engagement (e.g. singing or moving the body with the music) in people with advanced Alzheimer’s disease.
Design/methodology/approach
The program was implemented with 20 participants according to a non-concurrent multiple baseline design across participants. The participants were provided with a tablet whose screen worked as a sensor. During the intervention, sensor activations by hand responses led the tablet to present 10 s segments of preferred songs; an absence of sensor activation led the tablet to produce a prompt.
Findings
The participants’ mean frequencies of hand responses (i.e. sensor activations) per 5 min session increased from mostly zero during baseline to between about 9 and 20 during the intervention. The mean percentages of observation intervals with participants’ positive engagement increased from 0 to 12 during the baseline to between 13 and 55 during the intervention. The differences between baseline and intervention data were statistically significant for all participants.
Originality/value
A tablet-based program, such as that used in this study, may help people with advanced Alzheimer’s disease develop specific music-related responses and positive engagement.
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