The Use of Physical Activity Outcomes in Rehabilitation Interventions for Lower Limb Amputees: a Systematic Review.

BACKGROUND: Interventions which have focused on improving the physical activity of individuals with lower limb amputation can be mostly categorized into behavioural-based and prosthetic-based interventions. The aim of this review was to assess the quality of these interventions, and to identify the key gaps in research in this field. METHODOLOGY: The databases of Scopus, Pubmed, Embase, Medline and Web of Science were searched between September and December of 2019 for articles relating to physical activity, amputees and interventions. Articles were assessed quantitively based on internal validity, external validity and intervention intensity. FINDINGS: Sixteen articles (5 behavioural, 11 prosthetic) were assessed. Both approaches had comparable methodological quality and mixed efficacy for producing a significant change in physical activity outcomes. Almost all interventions used a simplistic measurement of activity as their outcome. CONCLUSIONS: There is an insufficient amount of studies to assess the overall efficacy of behavioural interventions in regard to how they impact on physical activity behaviour. However, the increase of quality of the methodology in the more recent studies could indicate that future interventions will retain similar levels of quality. Prosthetic interventions have shown no major improvement in efficacy compared to similar reviews and may need to utilise more advanced prosthetic components to attain significant changes in physical activity. Activity outcomes should expand into more complex activity measurements to properly understand the physical activity profile of people with lower limb amputation.

Histone deacetylase (HDAC) 1 and 2 complexes regulate both histone acetylation and crotonylation in vivo.

Proteomic analysis of histones has shown that they are subject to a superabundance of acylations, which extend far beyond acetylation, to include: crotonylation, propionylation, butyrylation, malonylation, succinylation, ß-hydroxybutyrylation and 2-hydroxyisobutyrylation. To date, much of the functional data has focussed on histone crotonylation which, similar to acetylation, has been associated with positive gene regulation and is added by the acyltransferase, p300. Although Sirtuins 1-3, along with HDAC3, have been shown to possess decrotonylase activity in vitro, there is relatively little known about the regulation of histone crotonylation in vivo. Here we show that Histone Deacetylase 1 and 2 (HDAC1/2), the catalytic core of numerous co-repressor complexes, are important histone decrotonylase enzymes. A ternary complex of HDAC1/CoREST1/LSD1 is able to hydrolyse both histone H3 Lys18-acetyl (H3K18ac) and H3 Lys18-crotonyl (H3K18cr) peptide substrates. Genetic deletion of HDAC1/2 in ES cells increases global levels of histone crotonylation and causes an 85% reduction in total decrotonylase activity. Furthermore, we mapped H3K18cr in cells using ChIP-seq, with and without HDAC1/2, and observed increased levels of crotonylation, which largely overlaps with H3K18ac in the vicinity of transcriptional start sites. Collectively, our data indicate that HDAC1/2 containing complexes are critical regulators of histone crotonylation in vivo.