To 'take their place among the productive members of society': Vocational rehabilitation of WWI wounded at Erskine.

In 1916, the foundation of the Princess Louise Scottish Hospital for Limbless Sailors and Soldiers (still in existence today as Erskine), on the banks of the River Clyde in Scotland, was a direct response to the need for specialised medical facilities to deal with the unprecedented number of injured service personnel returning from the Great War. At the hospital, the West of Scotland medical and industrial communities came together to mend broken bodies with prosthetic technology, as well as physical and mental rehabilitation to prepare the limbless to re-enter the job market. This paper explores the establishment of manual therapy workshops at Erskine and how such programmes of vocational rehabilitation were culturally informed by the concerns and anxieties of both the military and civilian populations of the First World War-era.

Rapid estrogen receptor-alpha activation improves ischemic tolerance in aged female rats through a novel protein kinase C epsilon-dependent mechanism.

The effects of estrogen deficiency on the loss of cardioprotection with advancing age are complex and poorly understood. A major focus of the current study was to uncover a cardioprotective role for rapid, nongenomic estrogen receptor (ER) signaling in the aged female myocardium. We hypothesized that selective ERalpha activation in aged females would reduce infarct size in part, through reversal of age-associated reductions in mitochondrial protein kinase Cepsilon (PKCepsilon). Hearts isolated from adult (6 month old) and aged (23-24 months old) female F344 rats with ovaries removed (n = 20 per group) were subjected to ischemia/reperfusion (47 min global ischemia). Rats were injected sc with the ERalpha agonist propylpyrazole triol (PPT) or vehicle 45 min before heart isolation (5 microg/kg). Infarct size was greatest in aged vs. adult ovariectomized rats, significantly reduced by PPT, and the protection reversed by prior administration of the ER inhibitor ICI 182,780 (3 mg/kg). Increased ERalpha particulate targeting occurred after PPT in conjunction with reversal of age-related reductions in nuclear PKCepsilon, mitochondrial PKCepsilon and pAkt (P < 0.05). PPT also increased mRNA levels for the PKCepsilon anchoring protein, receptor for activated C kinase2 (RACK2; P < 0.05). Our data suggest, for the first time, that selective ERalpha activation reduces ischemic injury in the aged, estrogen-deficient heart through a mechanism involving nongenomic redistribution of ERalpha and PKCepsilon activation. A novel feed-forward transcriptional mechanism to potentially enhance PKCepsilon-RACK2 interactions was also observed. Collectively, our findings may provide key insight into developing targeted therapeutic interventions in postmenopausal women to reduce ischemia/reperfusion injury, including selective ERalpha mimetics.

Helicobacter pylori and toll-like receptor agonists induce syndecan-4 expression in an NF-kappaB-dependent manner.

The syndecans are a family of transmembrane heparan sulfate proteoglycans (HSPG) that have been implicated in a wide variety of biological functions including the regulation of growth factor signaling, adhesion, tumorigenesis, and inflammation. In the current studies, we examined the regulation of syndecan-4 gene expression in gastric epithelial cells and macrophages in response to infection with live Helicobacter pylori and purified toll-like receptor (TLR) agonists. H. pylori, PAM3CSK4 (a TLR2 agonist), and Escherichia coli flagellin (a TLR5 agonist) all induced the rapid expression of syndecan-4 mRNA in MKN45 gastric epithelial cells. Similarly, lipopolysaccharide (LPS) (a TLR4 agonist) also induced the expression of syndecan-4 in macrophages. The H. pylori- and TLR-induced increase in syndecan-4 mRNA was blocked by the proteosome inhibitor MG-132 suggesting a role for nuclear factor kappaB (NF-kappaB) in the regulation of syndecan-4 gene expression. An 895-bp fragment of the human syndecan-4 promoter was cloned upstream of the luciferase reporter. When transfected into MKN45 cells, the activity of this promoter was inducible by H. pylori and TLR agonists. Inducible activity of the syndecan-4 promoter was blocked by cotransfection with a dominant negative IkappaBalpha expression plasmid. Electrophoretic mobility shift assays (EMSA) demonstrated the presence of a highly conserved NF-kappaB-binding site. Mutation of this site within the context of the full-length syndecan-4 promoter resulted in a complete loss of responsiveness to H. pylori and TLR agonists. These results thus demonstrate that the response of the syndecan-4 gene to infectious agents, or their products, is a direct result of NF-kappaB binding to the promoter and induction of de novo transcription.