Recommendations to Enhance Physical Health for Individuals with Severe Mental Illness in Canadian Healthcare Organizations.

As Canadians with severe mental illness remain underserved and experience a high burden of physical health challenges and premature mortality, there is an unprecedented need to provide better physical healthcare to this population. Ways of addressing this gap include the delivery of physical healthcare in mental health settings ("reverse integration"). However, there is limited guidance on how to enact this integration. In this article, we outline the development of an integrated care strategy in Canada's largest mental health hospital and discuss system- and policy-level recommendations that healthcare organizations could consider in their initiatives.

Integrin-linked kinase is required for TGF-ß1 induction of dermal myofibroblast differentiation.

Cutaneous repair after injury requires activation of resident dermal fibroblasts and their transition to myofibroblasts. The key stimuli for myofibroblast formation are activation of transforming growth factor-ß (TGF-ß) receptors and mechanotransduction mediated by integrins and associated proteins. We investigated the role of integrin-linked kinase (ILK) in TGF-ß1 induction of dermal fibroblast transition to myofibroblasts. ILK-deficient fibroblasts treated with TGF-ß1 exhibited attenuation of Smad 2 and 3 phosphorylation, accompanied by impaired transcriptional activation of Smad targets, such as α-smooth muscle actin. These alterations were not limited to Smad-associated TGF-ß1 responses, as stimulation of noncanonical mitogen-activated protein kinase pathways by this growth factor was also diminished in the absence of ILK. ILK-deficient fibroblasts exhibited abnormalities in the actin cytoskeleton, and did not form supermature focal adhesions or contractile F-actin stress fibers, indicating a severe impairment in their capacity to differentiate into myofibroblasts. These defects extended to the inability of cells to contract extracellular matrices when embedded in collagen lattices. We conclude that ILK is necessary to transduce signals implicated in the transition of dermal fibroblasts to myofibroblasts originating from matrix substrates and TGF-ß1.