Ageing and Mental Health in Canada: Perspectives from Law, Policy, and Longitudinal Research.

Canada is a relatively young, geographically-diverse country, with a larger proportion of the population aged over 65 than under 15. Increasing alongside the number of ageing Canadians is the number of older adults that live with mental health challenges. Across the life course, one in five Canadians will experience a mental health disorder with many more living with subclinical symptoms. For these individuals, their lived experience may be directly impacted by the contemporary laws and policies governing mental illness. Examining and reviewing the historical context of mental health and older adults, we provide insights into the evolving landscape of Canadian mental health law and policy, paternalistic roots in the infancy of the country, into modern foci on equity and diversity. Progressing in parallel to changes in mental health policy has been the advancement of mental health research, particularly through longitudinal studies of ageing. Although acting through different mechanisms, the evolution of Canadian mental health law, policy, and research has had, and continues to have, considerable impacts on the substantial proportion of Canadians living with mental health challenges.

Physical activity, eating traits and weight in young adulthood: a cross-sectional and longitudinal study.

OBJECTIVE: To investigate the association between eating traits (e.g. dietary restraint or opportunistic eating) and weight - both cross-sectionally and longitudinally - and whether physical activity (PA) moderates these associations. METHODS: Two-hundred seventy young adults (21-35 years; BMI: 25.40 kg/m2 [SD = 3.90 kg/m2]; 48.90% female) participated in this 12-month observational cohort study. Cognitive Restraint (CR), Disinhibition (DI) and Hunger (HU) were measured using the Three-Factor Eating Questionnaire at baseline and 12 months. Participants were measured at quarterly intervals for objectively measured PA and anthropometrics. Cross-sectional and longitudinal models determined if eating traits were associated with weight or weight change, and whether these associations were moderated by PA. RESULTS: At baseline, higher CR (B = 0.429, p < 0.01) and DI (B = 0.942, p < 0.01) were associated with higher weight. The associations of DI (B = -0.008 p = 0.02) and HU (B = -0.006, p = 0.04) with weight were moderated by PA at baseline. The longitudinal model for CR determined PA altered the relationship between change in CR and weight change (B = 0.004, p < 0.01). CONCLUSIONS: Eating traits and PA are associated with weight and weight change. However, to elucidate how PA and eating traits directly affect weight changes, future weight loss interventions should investigate whether improving eating traits and concomitantly increasing PA amplify weight loss.

Structure of a specific peptide complex of the carboxy-terminal SH2 domain from the p85 alpha subunit of phosphatidylinositol 3-kinase.

We have determined the solution structure of the C-terminal SH2 domain of the p85 alpha subunit of human phosphatidylinositol (PI) 3-kinase (EC 2.7.1.137) in complex with a phosphorylated tyrosine pentapeptide sequence from the platelet-derived growth factor receptor using heteronuclear nuclear magnetic resonance spectroscopy. Overall, the structure is similar to other SH2 domain complexes, but displays different detail interactions within the phosphotyrosine binding site and in the recognition site for the +3 methionine residue of the peptide, the side chain of which inserts into a particularly deep and narrow pocket which is displaced relative to that of other SH2 domains. The contacts made within this +3 pocket provide the structural basis for the strong selection for methionine at this position which characterizes the SH2 domains of PI3-kinase. Comparison with spectral and structural features of the uncomplexed domain shows that the long BG loop becomes less mobile in the presence of the bound peptide. In contrast, extreme resonance broadening encountered for most residues in the beta D', beta E and beta F strands and associated connecting loops of the domain in the absence of peptide persists in the complex, implying conformational averaging in this part of the molecule on a microsecond-to-millisecond time scale.

Antagonists of bombesin/gastrin releasing peptide based on [D-Ala24]GRP(20-26)-heptapeptide. Modifications leading to potent analogues with prolonged duration of action.

Analogues of gastrin releasing peptide (GRP) and bombesin based on His-Trp-Ala-Val-D-Ala-His-Leu, the 20-26 heptapeptide sequence of [D-Ala24]GRP, have been synthesized and tested in vitro for their ability to inhibit GRP (18-27)-induced mitogenesis in Swiss 3T3 cells. Compounds identified as potent antagonists in this test system were also tested in vivo for their ability to inhibit bombesin-induced amylase secretion in rats. The Trp-Ala-Val sequence was found to be a very important feature of the antagonist activity; most substitutions in this region led either to much less potent or inactive analogues. In contrast, amino acid replacements in other parts of the molecule were more tolerated and sometimes led to marked increases in the in vitro and in vivo activity. The most potent analogues were obtained by replacing Leu26 by MeLeu and His25 by Lys(X) where X = Z, PhCO, PhCH2CO or Ph(CH2)2CO. Thus 4-pyridylcarbonyl-His-Trp-Ala-Val-D-Ala-Lys(CO-CH2-CH2-Ph)-Leu- NHMe (86) and 4-pyridylcarbonyl-His-Trp-Ala-Val-D-Ala-Lys(Z)-MeLeu-OMe (87) had IC50 values of less than 20 micrograms/kg s.c. in vivo, and their effects lasted for more than 3 hr.