Intracellular IL-1α-binding proteins contribute to biological functions of endogenous IL-1α in systemic sclerosis fibroblasts

The aberrant production of precursor IL-1α (pre-IL-1α) in skin fibroblasts that are derived from systemic sclerosis (SSc) is associated with the induction of IL-6 and procollagen, which contributes to the fibrosis of SSc. However, little is understood about how intracellular pre-IL-1α regulates the expression of the other molecules in fibroblasts. We report here that pre-IL-1α can form a complex with IL-1α-binding proteins that is translocated into the nuclei of fibroblasts. Immunoprecipitation that used anti-human IL-1α Ab and (35)S-labeled nuclear extracts of fibroblasts showed three specific bands (≈31, 35, and 65 kDa). The 31-kDa molecule was identified as pre-IL-1α, and the 35- and 65-kDa molecules might be pre-IL-1α-binding proteins. A partial sequencing for the 10 aa from the N-terminals of the molecules showed 100% homology for HAX-1 (HS1-associated protein X-1) and IL-1 receptor type II (IL-1RII). Suppression of the genes of HAX-1 or IL-1RII induced the inhibitory effects of IL-1 signal transduction, including production of IL-6 and procollagen, by fibroblasts. In particular, pre-IL-1α was not translocated into the nucleus by an inhibition of HAX-1. These findings reveal that nuclear localization of pre-IL-1α depends on the binding to HAX-1 and that biological activities might be elicited by the binding to both HAX-1 and IL-1RII in SSc fibroblasts

Analysis of discharge documentation for older adults living with dementia: A cohort study.

BackgroundOlder adults living with dementia frequently transition between healthcare settings. Care transitions increase vulnerability and risk of iatrogenic harm.Aim and objectiveTo examine the quality of transitional care arrangements within discharge documentation for older people living with dementia.DesignSecondary analysis of cohort study data.MethodA secondary analysis of the IDEAL Study [ACTRN12612001164886] discharge documents, following the STROBE guidelines. Participants had a confirmed diagnosis of dementia and were discharged from hospital to a nursing home. An audit tool was used to extract the data. This was developed through a synthesis of existing tools and finalised by an expert panel. The analysis assessed the quality of discharge documentation, in the context of transitional care needs, and presented results using descriptive statistics. Functional ability; physical health; cognition and mental health; medications; and socio environmental factors were assessed.ResultsSixty participants were included in analyses, and half were male (52%), with a total participant mean age of 83 (SD 8.7) years. There was wide variability in the quality of core discharge information, ranging from excellent (37%), adequate (43%) to poor (20%). A sub-group of these core discharge documentation elements that detailed the participants transitional care needs were rated as follows: excellent (17%), adequate (46%) and poor (37%).ConclusionDischarge documentation fails to meet needs of people living with dementia. Improving the quality of discharge documentation for people living with dementia transitioning from hospital to nursing home is critical to provide safe and quality care.Relevance to clinical practiceThere is a need for safe, timely, accurate and comprehensive discharge information to ensure the safety of people living with dementia and prevent adverse harm