420 research outputs found

    Calcium phosphate particles stimulate interleukin-1β release from human vascular smooth muscle cells: A role for spleen tyrosine kinase and exosome release

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    Aims: Calcium phosphate (CaP) particle deposits are found in several inflammatory diseases including atherosclerosis and osteoarthritis. CaP, and other forms of crystals and particles, can promote inflammasome formation in macrophages leading to caspase-1 activation and secretion of mature interleukin-1β (IL-1β). Given the close association of small CaP particles with vascular smooth muscle cells (VSMCs) in atherosclerotic fibrous caps, we aimed to determine if CaP particles affected pro-inflammatory signalling in human VSMCs. Methods and results: Using ELISA to measure IL-1β release from VSMCs, we demonstrated that CaP particles stimulated IL-1β release from proliferating and senescent human VSMCs, but with substantially greater IL-1β release from senescent cells; this required caspase-1 activity but not LPS-priming of cells. Potential inflammasome agonists including ATP, nigericin and monosodium urate crystals did not stimulate IL-1β release from VSMCs. Western blot analysis demonstrated that CaP particles induced rapid activation of spleen tyrosine kinase (SYK) (increased phospho-Y525/526). The SYK inhibitor R406 reduced IL-1β release and caspase-1 activation in CaP particle-treated VSMCs, indicating that SYK activation occurs upstream of and is required for caspase-1 activation. In addition, IL-1β and caspase-1 colocalised in intracellular endosome-like vesicles and we detected IL-1β in exosomes isolated from VSMC media. Furthermore, CaP particle treatment stimulated exosome secretion by VSMCs in a SYK-dependent manner, while the exosome-release inhibitor spiroepoxide reduced IL-1β release. Conclusions: CaP particles stimulate SYK and caspase-1 activation in VSMCs, leading to the release of IL-1β, at least in part via exosomes. These novel findings in human VSMCs highlight the pro-inflammatory and procalcific potential of microcalcification

    Social representations of diagnosis in the consultation

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    Observations of physiotherapy consultations and qualitative interviews with patients were conducted to explore the clinical explanation for sciatic pain. We report three themes which illustrate the contested and negotiated order of the clinical explanation: anchoring, resistance and normalisation. We show using the theory of social representations how the social order in the physiotherapy consultation is maintained, contested and rearticulated. We highlight the importance of agency in patients’ ability to resist the clinical explanation and in turn shape the clinical discourse within the consultation. Social representations offer insights into how the world is viewed by different individuals, in our case physiotherapists and patients with sciatic pain symptoms. The negotiation about the diagnosis reveals the malleable and socially constructed nature of pain and the meaning making process underpinning it. The study has implications for understanding inequalities in the consultation and the key ingredients of consensus

    Severe acute respiratory infection caused by swine influenza virus in a child necessitating extracorporeal membrane oxygenation (ECMO), the Netherlands, October 2016.

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    In October 2016, a severe infection with swine influenza A(H1N1) virus of the Eurasian avian lineage occurred in a child with a previous history of eczema in the Netherlands, following contact to pigs. The patient's condition deteriorated rapidly and required life support through extracorporeal membrane oxygenation. After start of oseltamivir treatment and removal of mucus plugs, the patient fully recovered. Monitoring of more than 80 close unprotected contacts revealed no secondary cases

    Infant mortality in mid-19th century Amsterdam:Religion, social class, and space

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    This study uses a unique historical GIS dataset compiled from birth, death, and population register records for infants born in the city of Amsterdam in 1851 linked to micro‐level spatial data on housing, infrastructure, and health care. Cox's proportional hazards models and the concept of egocentric neighbourhoods were used to analyse the effects of various sociodemographic characteristics, residential environment, water supply, and health‐care variables on infant mortality and stillbirth. The analyses confirm the favourable position of the Jewish population with respect to infant mortality as found in other studies and show the unfavourable position of orthodox Protestant minorities. Infant mortality rate differences are much smaller between social classes than between religions. The exact role of housing and neighbourhood conditions vis‐a‐vis infant mortality is still unclear; however, we ascertained that effects of environmental conditions are more pronounced in later stages of infancy and less important in the early stages of infancy
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