β-Glucosylceramide From Allergic Mothers Enhances Offspring Responsiveness to Allergen

In animals and humans, offspring of allergic mothers have increased responsiveness to allergen and the allergen-specificity of the offspring can be different than that of the mother. In our preclinical models, the mother's allergic responses influence development of the fetus and offspring by elevating numbers of cells in dendritic cell subsets. A major question is the identity of maternal factors of allergic mothers that alter offspring development of responsiveness to allergen. Lipids are altered during allergic responses and lipids are transported to the fetus for growth and formation of fetal membranes. We hypothesized that pro-inflammatory lipids, that are elevated in allergic mothers, are transported to the fetus and regulate fetal immune development. We demonstrate in this report that there was a significant 2-fold increase in β-glucosylceramides (βGlcCer) in allergic mothers, the fetal liver and her offspring. The βGlcCer were transported from mother's plasma, across the placenta, to the fetus and in breastmilk to the offspring. Administration of βGlcCer to non-allergic mothers was sufficient for offspring responses to allergen. Importantly, maternal administration of a clinically relevant pharmacological inhibitor of βGlcCer synthase returned βGlcCer to normal levels in the allergic mothers and her offspring and blocked the offspring increase in dendritic cell subsets and offspring allergen responsiveness. In summary, allergic mothers had increased βGlcCer that was transported to offspring and mediated increases in offspring DCs and responsiveness to allergen. These data have a significant impact on our understanding of mechanisms for development of allergies in offspring of allergic mothers and have the potential to lead to novel interventions that significantly impact risk for allergic disease early in life

Improving office workers' mental health and cognition : a 3-arm cluster randomized controlled trial targeting physical activity and sedentary behavior in multi-component interventions

Background Physically inactive and sedentary lifestyles are negatively related to both mental health and cognition. For office-workers, who spend two-thirds of their workday sitting, it is important to improve these lifestyles. The aim of this study is to assess the effectiveness of multi-component interventions, incorporating individual, environmental and organizational changes, to increase physical activity or reduce sedentary behavior among office-workers in order to improve mental health and cognition. Methods a 3-arm, clustered randomized controlled trial (RCT) with waiting list control group amongst adult office-workers of two large Swedish companies. Cluster teams will be randomized into 6-month interventions or to a passive waiting list control group which will receive the allocated intervention with a 6-month delay. Two multicomponent interventions will be studied of which one focuses on improving physical activity and the other on reducing sedentary behavior. Both interventions include 5 sessions of motivational counselling. In the physical activity intervention persons also get access to a gym and team leaders will organize lunch walks and encourage to exercise. In the sedentary behavior intervention standing- and walking meetings will be implemented and team leaders will encourage to reduce sitting. The recruitment target is 110 office-workers per arm (330 in total). Measurements will be repeated every 6months for a total intended duration of 24months. Proximal main outcomes are physical activity measured with accelerometers and sedentary behavior with inclinometers. Distal outcomes are self-reported mental health and a cognition test battery. Additional outcomes will include cardiovascular fitness, body composition, sleep, self-reported physical activity and sedentary behavior, other health habits, physical health, and working mechanisms from blood samples and questionnaires. Discussion This cluster RCT will contribute to the currently available evidence by comparing the effectiveness of multi-component interventions targeting physical activity or sedentary behavior with the end goal of improving mental health and cognition. This study is strong in its cluster randomized design, numerous objective outcome measures and long-term follow-up. The exact content of the interventions has been defined by combining theory with results from a larger research project as well as having a continuous dialogue with the involved companies.Fysisk aktivitet och hälsosamma hjärnfunktioner bland kontorsarbetare: Delprojekt 3, Långsiktiga interventione