The androgen receptor (AR) is a ligand-dependent transcription factor which is part o the nuclear receptor superfamily. Binding of androgens testosterone or 5 a-reduced dihydrotestosterone activates ...the receptor causing it to localise to the nucleus where it binds to specific DNA androgen response elements in androgen-regulated genes and activates transcription. The N-terminal domain (NTD) of the AR contains several polyamino acid repeat sequences. The polyglycine repeat and one of the polyglutamine (poly-Q) repeats are polymorphic and changes in length are associated with disease. Expansion of the poly-Q tract in the AR NTD causes spatial bulbar muscular atrophy (SBMA) or Kennedy’s disease. SBMA is one of a group of nine neurodegenerative diseases caused by a poly-Q repeat tract expansion. The function of the majority of poly-Q disease proteins is unknown hence the AR provides an opportunity to investigate poly-Q polymorphic effects on protein structure and function. Structural analysis indicates an expansion of the poly-Q tract increases a-helical secondary structure content in the AR NTD. An increase in poly-Q tract length also enhances binding to the C-terminal domain of p160 co-activator proteins SRC-1a and TIF2 as well as to the TFIID component TAFII130 drosophila homolog dTAFII110. Phosphorylation of the AR NTD by kinases CKII, GSK-3, MAPK and PKA is enhanced by deletion of the poly-Q tract. MAP kinase phosphorylation of the AR NTD is also increased by the expansion of the poly-Q tract. An increase in protein structure caused by expansion of the poly-Q tract in the AR NTD correlates to enhanced protein binding and changes in MAPK phosphorylation which, may influence receptor activity and play a role in the pathogenesis of SBMA.
Clinical guidelines are a feature of any health care systems. They have the potential to improve clinical practice, but a well-developed evidence base to guide the choice of strategies to ...disseminate and implement guidelines is currently lacking. Psychology has produced theories that have been successful in explaining behaviour and behaviour change across circumstances. They help to explain how interventions to implement guidelines operate to change clinical practice (a form of behaviour), and the circumstances in which interventions may be effective. Aims: 1) To explore the theoretical base of dissemination and implementation strategies currently used in research studies; 2) To consider ways of using psychological theories in implementation research. Study 1: A review of theory use in a systematically selected sample of 235 studies of interventions to disseminate and implement guidelines. Studies were classified according to level and stage of theory use. Fifty-three studies (23%) were judged to have used theories, of which fourteen (6%) were explicitly theory-based. In the majority of cases theory was used to guide the choice or design of interventions. Study 2: The Theory of Planned Behaviour (The TPB) was used alongside a trial of an intervention to implement preventive health care practice among Canadian family physicians (n = 73). The TPB explained 54% and 34% of the variance in intentions to offer lifestyle counselling and screening tests respectively. Physicians possessed strong attitudes and intentions towards offering preventive procedures to patients but perceptions of control over the behaviours were lower. Use of the TPB to guide the choice, design and evaluation of interventions to change practice was considered. Conclusion: Psychological theories represent a useful tool for the development of effective interventions to implement clinical guidelines. More studies that make explicit use of theory are needed. Recommendations for the conduct of theory-based research are discussed.
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