ABSTRACT
Comorbid symptoms such as post-traumatic stress and pain are common barriers to optimal self-management among veterans with type 2 diabetes. Additionally, self-management behaviors occur in the context of veterans' daily routines and social environments. This study evaluated the feasibility and acceptability of ecological momentary assessment (EMA) among veterans with type 2 diabetes. Ten veterans with type 2 diabetes were asked to respond to random EMA surveys during preprogrammed intervals five times per day for 14 days. EMA surveys were delivered via a mobile application and assessed momentary physical location, activities, social interactions, mood, stress, and pain. The last survey of each day included additional items about daily post-traumatic stress symptoms, diabetes distress, social support, physical activity, self-management behaviors, and functioning. Participants completed interviews assessing their experience in the study and barriers to responding and indicated their likelihood of participating in similar studies. The mean survey response rate was 96%, providing 675 observations. The majority of participants completed the five momentary surveys in <1 minute and the daily EMA surveys in <5 minutes. Results revealed substantial individual day-to-day variability across symptoms and self-management behaviors that is not captured by aggregated means across all participants. Participants generally reported enjoying responding to surveys and experiencing few barriers. Nine of 10 participants reported being "extremely likely" to participate in a similar study. These pilot data suggest that intensive EMA designs are feasible and acceptable for veterans with type 2 diabetes and can inform the design of future larger studies.
ABSTRACT
Neighboring sequences of a gene can influence its expression. In the phenomenon known as transcriptional interference, transcription at one region in the genome can repress transcription at a nearby region in cis Transcriptional interference occurs at a number of eukaryotic loci, including the alcohol dehydrogenase (Adh) gene in Drosophila melanogasterAdh is regulated by two promoters, which are distinct in their developmental timing of activation. It has been shown using transgene insertion that when the promoter distal from the Adh start codon is deleted, transcription from the proximal promoter becomes de-regulated. As a result, the Adh proximal promoter, which is normally active only during the early larval stages, becomes abnormally activated in adults. Whether this type of regulation occurs in the endogenous Adh context, however, remains unclear. Here, we employed the CRISPR/Cas9 system to edit the endogenous Adh locus and found that removal of the distal promoter also resulted in the untimely expression of the proximal promoter-driven mRNA isoform in adults, albeit at lower levels than previously reported. Importantly, transcription from the distal promoter was sufficient to repress proximal transcription in larvae, and the degree of this repression was dependent on the degree of distal promoter activity. Finally, upregulation of the distal Adh transcript led to the enrichment of histone 3 lysine 36 trimethylation over the Adh proximal promoter. We conclude that the endogenous Adh locus is developmentally regulated by transcriptional interference in a tunable manner.
