BackgroundBoth type I interferon (IFN), also known as IFN-α and tumor necrosis factor alpha (TNF-α) have been implicated in the pathogenesis of sarcoidosis. We investigated serum levels of these cytokines in a large multi-ancestral sarcoidosis population to determine correlations between cytokine levels and disease phenotypes.MethodsWe studied serum samples from 98 patients with sarcoidosis, including 71 patients of African-American ancestry and 27 patients of European-American ancestry. Serum type I IFN was measured using a sensitive reporter cell assay and serum TNF-α was measured using a commercial ELISA kit. Clinical data including presence or absence of neurologic, cardiac, and severe pulmonary manifestations of sarcoidosis were abstracted from medical records. Twenty age-matched non-autoimmune controls were also studied from each ancestral background. Differences in cytokine levels between groups were analyzed with Mann-Whitney U test, and correlations were assessed using Spearman's rho. Multivariate logistic regression models were used to detect associations between cytokines and clinical manifestations.ResultsSignificant differences in cytokine levels were observed between African- and European-American patients with sarcoidosis. In African-Americans, serum TNF-α levels were significantly higher relative to matched controls (P = 0.039), and patients with neurologic disease had significantly higher TNF-α than patients lacking this manifestation (P = 0.022). In European-Americans, serum type I IFN activity was higher in sarcoidosis cases as compared to matched controls, and patients with extra-pulmonary disease represented a high serum IFN subgroup (P = 0.0032). None of the associations observed were shared between the two ancestral groups.ConclusionsOur data indicate that significant associations between serum levels of TNF-α and type I IFN and clinical manifestations exist in a sarcoidosis cohort that differ significantly by self-reported ancestry. In each ancestral background, the cytokine elevated in patients with sarcoidosis was also associated with a particular disease phenotype. These findings may relate to ancestral differences in the molecular pathogenesis of this heterogeneous disease.
The English Tonic Sol-fa System originated in Norwich, England, in the 1830s. Although credit for this development is frequently given to John Curwen, the author was Sarah Glover, a Sunday school music director. Glover's system began with simplified notation for sol-fa syllables and rhythms. The system and its accompanying teaching strategies were discovered in 1841 by John Curwen who subsequently popularised and adapted them. Conflict arose between the two educators regarding the modifications Curwen made in the system, yet the impact of Glover's work on Curwen and, eventually, music education in general, cannot be disputed.
The English Tonic Sol-fa System originated in Norwich, England, in the 1930s. Although credit for this development is frequently given to John Curwen, the author was Sarah Glover, a Sunday school music director. Glover's system began with simplified notation for sol-fa syllables and rhythms. The system and its accompanying teaching strategies were discovered in 1841 by John Curwen who subsequently popularized and adapted them. Conflict arose between the two educators regarding the modifications Curwen made in the system, yet the impact of Glover's work on Curwen and, eventually, music education in general, cannot be disputed.
Excess weight gain is an increasing burden on individuals, societies and healthcare providers. The role of very low calorie diets (VLCD) in the treatment of overweight and obese people with diabetes is considered within the framework of a partnership between healthcare providers, a commercial organisation and the patient.
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