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Contains fulltext : 232522.pdf (Publisher’s version ) (Open Access), BCG vaccination can strengthen protection against pathogens through the induction of epigenetic and metabolic reprogramming of innate immune cells, a process called trained immunity. We and others recently demonstrated that mucosal or intravenous BCG better protects rhesus macaques from Mycobacterium tuberculosis infection and TB disease than standard intradermal vaccination, correlating with local adaptive immune signatures. In line with prior mouse data, here, we show in rhesus macaques that intravenous BCG enhances innate cytokine production associated with changes in H3K27 acetylation typical of trained immunity. Alternative delivery of BCG does not alter the cytokine production of unfractionated bronchial lavage cells. However, mucosal but not intradermal vaccination, either with BCG or the M. tuberculosis-derived candidate MTBVAC, enhances innate cytokine production by blood- and bone marrow-derived monocytes associated with metabolic rewiring, typical of trained immunity. These results provide support to strategies for improving TB vaccination and, more broadly, modulating innate immunity via mucosal surfaces.

Introduction. Aldosterone decreases at high altitude (HA) but the effect of hypoxia on angiotensin converting-enzyme (ACE), a key step in the renin-angiotensin-aldosterone system, is unclear. Materials and Methods. We investigated the effects of exercise and acute normobaric hypoxia (NH, ~11.0% FiO2) on nine participants and six controls undertaking the same exercise at sea-level (SL). NH exposure lasted 5 hours with 90 min of submaximal treadmill walking. Blood samples for aldosterone, ACE and cortisol were taken throughout exposure and at rest during a trek to HA (5140 m) in eight separate participants. Results. There was no difference in cortisol or aldosterone between groups pre-exercise. Aldosterone rose with exercise to a greater extent at SL than in NH (post-exercise: 700±325 vs 335±238 pmol/L, mean ± SD, p=0.044). Conversely, cortisol rose to a greater extent in NH (post-exercise: 734±165 vs 344±159 nmol/L, mean ± SD, p=0.001). There were no differences in ACE activity. During the trek to HA resting aldosterone and cortisol reduced with no change in ACE. Conclusion. Acute NH subdues the exercise-associated rise in aldosterone but stimulates cortisol, whereas prolonged exposure at HA reduces both resting aldosterone and cortisol. As ACE activity was unchanged in both environments this is not the mechanism underlying the fall in aldosterone.

© 2017 Elsevier Ltd Exit from work leads to different effects on health, partially depending on the socioeconomic status (SES) of people in the work exit. Several studies on the effects of exit from work on health across socioeconomic groups have been performed, but results are conflicting. The aim of this review is to systematically review the available evidence regarding the effects of exit from work on health in high and low socioeconomic groups. A systematic literature search was conducted using Pubmed, Embase, Web of Science, CINAHL and PsycINFO. Search terms related to exit from work, health, SES and design (prospective or retrospective). Articles were included if they focused on: exit from work (early/statutory retirement, unemployment or disability pension); health (general, physical or mental health and/or health behaviour); SES (educational, occupational and/or income level); and inclusion of stratified or interaction analyses to determine differences across socioeconomic groups. This search strategy resulted in 22 studies. For general, physical or mental health and health behaviour, 13 studies found more positive effects of exit from work on health among employees with a higher SES compared to employees with a lower SES. These effects were mainly found after early/statutory retirement. In conclusion, the effects of exit from work, or more specific the effects of early/statutory retirement on health are different across socioeconomic groups. However, the findings of this review should be interpreted with caution as the studies used heterogeneous health outcomes and on each health outcome a limited number of studies was included. Yet, the positive effects of exit from work on health are mainly present in higher socioeconomic groups. Therefore, public health policies should focus on improving health of employees with a lower SES, in particular after exit from work to decrease health inequalities.