Metabolome and lipidome derangements during a severe mast cell activation event in a patient with indolent systemic mastocytosis.

BACKGROUND: The number of mast cells in various organs is elevated manifold in individuals with systemic mastocytosis. Degranulation can lead to life-threatening symptomatology. No data about the alterations of the metabolome and lipidome during an attack have been published. OBJECTIVE: Our aim was to analyze changes in metabolomics and lipidomics during the acute phase of a severe mast cell activation event. METHODS: A total of 43 metabolites and 11 lipid classes comprising 200 subvariants from multiple plasma samples in duplicate, covering 72 hours of a severe mast cell activation attack with nausea and vomiting, were compared with 2 baseline samples by using quantitative liquid chromatography-mass spectrometry. RESULTS: A strong enterocyte dysfunction reflected in an almost 20-fold reduction in the functional small bowel length was extrapolated from strongly reduced ornithine and citrulline concentrations and was very likely secondary to severe endothelial cell dysfunction with hypoperfusion and extensive vascular leakage. Highly increased histamine and lactate concentrations accompanied the peak in clinical symptoms. Elevated asymmetric and symmetric dimethylarginine levels combined with reduced arginine levels compromised endothelial nitric oxide synthase activity and nitric oxide signaling. Specific and extensive depletion of many lysophosphatidylcholine variants indicates localized autotaxin activation and lysophosphatidic acid release. A strong correlation of clinical parameters with histamine concentrations and symptom reduction after 100-fold elevated plasma diamine oxidase concentrations implies that histamine is the key driver of the acute phase. CONCLUSIONS: Rapid elimination of elevated histamine concentrations through use of recombinant human diamine oxidase, supplementation of lysophosphatidylcholine for immunomodulation, inhibition of autotaxin activity, and/or blockade of lysophosphatidic acid receptors might represent new treatment options for life-threatening mast cell activation events.

Facets of Faith: Spirituality, Religiosity, and Parents of Individuals With Intellectual Disability.

Although faith has particular prominence in the contemporary American landscape, its intersection with disability and families has received little attention. We examined the spiritual and religious lives of 530 parents and caregivers of family members who have intellectual disability. For most participants, faith had clear relevance and was reflected in their congregational participation, beliefs, practices, and strength of faith. Yet considerable diversity was apparent in the ways in which each was evidenced, which included a modest number of families for whom this was not a salient aspect of their lives. Most participants identified ways in which their spirituality and religious participation contributed to their well-being. However, access to social supports through a local congregation was more muted. We address implications for professionals who support these families and congregations who welcome them. We also offer recommendations for expanding the opportunities and supports parents and caregivers need to flourish in their faith.

In their own words: the place of faith in the lives of young people with autism and intellectual disability.

Abstract Although the prominence of spirituality and religious connections among the people of the United States is well documented, little is known about the place of faith in the lives of youth with developmental disabilities. In this qualitative interview study, we examined the perspectives of 20 young people with intellectual disability or autism on their faith, spiritual expressions, and disability. Participants identified key spiritual expressions and themes reflecting the importance of faith in their lives. They also shared perceptions of their disability in the context of their faith, highlighting affirmation and acceptance of their disability. We offer recommendations to families, faith communities, and service systems for supporting the spiritual formation, expression, and connections of young people with disabilities.