22 research outputs found

    Human amnion epithelial cells rescue cell death via immunomodulation of microglia in a mouse model of perinatal brain injury

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    BACKGROUND: Human amnion epithelial cells (hAECs) are clonogenic and have been proposed to reduce inflammatory-induced tissue injury. Perturbation of the immune response is implicated in the pathogenesis of perinatal brain injury; modulating this response could thus be a novel therapy for treating or preventing such injury. The immunomodulatory properties of hAECs have been shown in other animal models, but a detailed investigation of the effects on brain immune cells following injury has not been undertaken. Here, we investigate the effects of hAECs on microglia, the first immune responders to injury within the brain. METHODS: We generated a mouse model combining neonatal inflammation and perinatal hyperoxia, both of which are risk factors associated with perinatal brain injury. On embryonic day 16 we administered lipopolysaccharide (LPS), or saline (control), intra-amniotically to C57Bl/6 J mouse pups. On postnatal day (P)0, LPS pups were placed in hyperoxia (65% oxygen) and control pups in normoxia for 14 days. Pups were given either hAECs or saline intravenously on P4. RESULTS: At P14, relative to controls, LPS and hyperoxia pups had reduced body weight, increased density of apoptotic cells (TUNEL) in the cortex, striatum and white matter, astrocytes (GFAP) in the white matter and activated microglia (CD68) in the cortex and striatum, but no change in total microglia density (Iba1). hAEC administration rescued the decreased body weight and reduced apoptosis and astrocyte areal coverage in the white matter, but increased the density of total and activated microglia. We then stimulated primary microglia (CD45(low)CD11b(+)) with LPS for 24 h, followed by co-culture with hAEC conditioned medium for 48 h. hAEC conditioned medium increased microglial phagocytic activity, decreased microglia apoptosis and decreased M1 activation markers (CD86). Stimulating hAECs for 24 h with LPS did not alter release of cytokines known to modulate microglia activity. CONCLUSIONS: These data demonstrate that hAECs can directly immunomodulate brain microglia, probably via release of trophic factors. This observation offers promise that hAECs may afford therapeutic utility in the management of perinatal brain injury

    Brain homeostasis: VEGF receptor 1 and 2—two unequal brothers in mind

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    Translated article: Einsatzerlebnisse, moralische Verletzungen, Werte und psychische Erkrankungen bei Einsatzsoldaten der Bundeswehr

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    <i>Hintergrund:</i> Soldaten sind in militĂ€rischen AuslandseinsĂ€tzen vielfĂ€ltigen belastenden Erlebnissen ausgesetzt, die zu erhöhten Raten an psychischen Erkrankungen fĂŒhren. Moralische Verletzungen und Wertorientierungen scheinen in der Pathogenese dieser Erkrankungen eine Rolle zu spielen. <i>Patienten und Methode:</i> 191 Bundeswehrsoldaten erhielten zum Ende eines Einsatzes in Afghanistan eine Skala zu Einsatzerfahrungen (MHAT), die Posttraumatic Stress Diagnostic Scale (PDS), den Patient Health Questionnaire (PHQ-D), die Moral Injury Events Scale sowie den Portrait Values Questionnaire (PVQ). In Regressionsanalysen wurden direkte Assoziationen von Einsatzstressoren und Wertorientierungen mit psychischen Syndromen untersucht. In einer Mediationsanalyse wurden moralische Verletzungen als Mediator zwischen Einsatzerleben und psychischen Erkrankungen betrachtet. <i>Ergebnisse:</i> Der einsatzbezogene Stressor «Konfrontation mit Not, Leid, Gewalt in der Bevölkerung» zeigte einen direkten signifikanten Einfluss auf psychische Erkrankungen. Moralische Verletzungen stellten eine differenziell vermittelnde Variable zwischen dem Stressor «Konfrontation mit Not, Leid, Gewalt in der Bevölkerung» und den psychischen Syndromen «posttraumatische Belastungsstörung» und «DepressivitĂ€t» einerseits und Alkoholmissbrauch andererseits dar. Keine signifikanten ZusammenhĂ€nge ergaben sich zwischen traditionellen Werthaltungen und psychischen Erkrankungen sowie zwischen traditionellen Werthaltungen und moralischen Verletzungen. <i>Schlussfolgerung:</i> Einsatzerlebnisse mit moralischer Dimension scheinen eine besonders starke Rolle in Bezug auf psychische Erkrankungen bei Bundeswehrsoldaten zu spielen. Der Effekt wird ĂŒber das Konstrukt moralischer Verletzungen vermittelt. Diese Ergebnisse können zur Weiterentwicklung prĂ€ventiver und therapeutischer Maßnahmen beitragen

    BMI and Employment: Is There an Overweight Premium?

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    Using pooled data from the Health Survey of England (HSE) and a semi-parametric regression model, this paper aims to estimate the relationship between body weight and employment probability. We show that employment probabilities do not follow a linear relationship and are highest at a body weight over the clinical threshold for overweight. Instead of an “obesity penalty” we find evidence of an “overweight premium”, especially in socially active jobs. These results suggests that there might exists an endogenous social norm governing body weight judgments and influencing employment prospects, which has been recently updated due to an increase in average body weight
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