Magnus Ludvigsson - Did Your Prince Ever Show Up
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When Margaret's first cousin King Inge the Younger died in 1125, Magnus claimed the throne as the eldest grandson of Inge the Elder. Magnus was recognized by the Geats (Göterna) of Gothenland, but according to the Westrogothic law, had to be accepted also by the Swea, another tribe to the north of the Geats. The Swea, however, had selected Ragnvald Knaphövde. According to Saxo Grammaticus, Ragnvald had shown disrespect towards the Geats by not taking a Geat hostage. As retaliation, Ragnvald was murdered by Magnus's supporters not long after.
Vitamin D status has also been linked with asthma development and control [303]. Recently, Litonjua showed that vitamin D has both in utero and post-natal effects on lung development and immune system development and function [304]. Adverse exposures in this critical period, such as low levels of serum 25(OH)D, might lead to developmental changes including reduced lung and airway growth and could therefore be a major importance for the development of asthma. Vitamin D appears to affect innate and adaptive immune system development through lymphocyte activation and proliferation, and T-helper cell differentiation [305]. Several studies showed that vitamin D deficiency in utero and in early life was associated with an increase in Th2 lymphocyte cells and a reduction in T regulatory cells and production of interleukin (IL)-10, which subsequently may activate pro-inflammatory cytokine production through macrophages and dendritic cells [306,307,308]. Consequently, several studies in vivo and in vitro showed that vitamin D supplementation inhibits the Th2 expression contrasting allergic diseases [309,310,311,312,313,314]. Furthermore, previous studies focused on the association between serum 25(OH)D levels and the expression of genes involved in the proliferation and cells differentiation, showing an anti-proliferative activity of vitamin D with consequently remodeling inhibition [309,310,311,312]. Experimental data suggests that vitamin D3 significantly overcame the inhibition of glucocorticoid-receptor expression by dexamethasone while IL-10 upregulated glucocorticoid-receptor expression by CD4+ T cells, suggesting potential mechanisms whereby these treatments may overcome poor glucocorticoid responsiveness [315]. About the role of vitamin D in the immunopathogenesis of allergic skin diseases, vitamin D induces the production of antimicrobial peptides, as beta-defensin and cathelicidin, causing a reduction of the bacterial infections that may exacerbate asthma and atopic dermatitis (AD) [316, 317]. Not yet fully understood is the role of vitamin D on eosinophilic airway inflammation. In a recent study low 25(OH)D levels were associated to high levels of fractional exhaled nitric oxide [318]. On the contrary, in a study on 3130 mother child pairs there was no association between 25(OH)D levels and fractional exhaled nitric oxide in the first month of life [319].
Three studies evaluated 25(OH)D levels related to severity of asthma assessed by Asthma Control Test [328,329,330]. The first two studies showed that 25(OH)D levels were inversely related to asthma severity, while Gergen et al. demonstrated a correlation only for Afro-Americans subjects.
It is still a matter for full debate whether supplementation with vitamin D in pediatric AD is worth, particularly in deficient patients. A recent large study found no evidence that genetically determined reduction in 25(OH)D levels conferred an increased risk for AD, suggesting that efforts to increase vitamin D are unlikely to reduce risks of the atopic disease [349]. However, there are also two reviews and meta-analyses, considering AD patients of all ages, showing that vitamin D supplementation is capable of a higher mean difference in severity of AD symptoms [350, 351]. Particularly, vitamin D supplementation decreased AD severity and improved its symptoms and clinical signs. In pediatric population there is some evidence about a favourable ef
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