Pediatr Rheumatol Online J
January 2024
Background: STING-associated vasculopathy with onset in infancy (SAVI) is a rare type I interferonopathy caused by heterozygous variants in the STING gene. In SAVI, STING variants confer a gain-of-function which causes overactivation of type I interferon (IFN) signaling leading to autoinflammation and various degrees of immunodeficiency and autoimmunity.
Case Presentation: We report the case of a 5 year old child and his mother, both of whom presented with systemic inflammatory symptoms yet widely varying organ involvement, disease course and therapeutic response.
J Allergy Clin Immunol
November 2023
Background: Genetic defects in components of inflammasomes can cause autoinflammation. Biallelic loss-of-function mutations in dipeptidyl peptidase 9 (DPP9), a negative regulator of the NLRP1 and CARD8 inflammasomes, have recently been shown to cause an inborn error of immunity characterized by pancytopenia, skin manifestations, and increased susceptibility to infections.
Objective: We sought to study the molecular basis of autoinflammation in a patient with severe infancy-onset hyperinflammation associated with signs of fulminant hemophagocytic lymphohistiocytosis.
Exogenous mesenchymal stromal cells (MSCs) ameliorate experimental bronchopulmonary dysplasia. Moreover, data from term-born animal models and human tracheal aspirate-derived cells suggest altered mesenchymal signaling in the pathophysiology of neonatal lung disease. We hypothesized that hyperoxia, a factor contributing to the development of bronchopulmonary dysplasia, perturbs human lung-resident MSC function.
View Article and Find Full Text PDFCommunity-based clergy are highly engaged in helping seriously ill patients address spiritual concerns at the end of life (EOL). While they desire EOL training, no data exist in guiding how to conceptualize a clergy-training program. The objective of this study was used to identify best practices in an EOL training program for community clergy.
View Article and Find Full Text PDFJ Health Care Chaplain
June 2016
There is a growing body of evidence investigating chaplaincy services. The purpose of this scoping review was to examine the empirical literature specific to the role of chaplaincy within health care published since 2009. Electronic searches of four databases were conducted in August 2015.
View Article and Find Full Text PDFGenome integrity is continuously challenged by the DNA damage that arises during normal cell metabolism. Biallelic mutations in the genes encoding the genome surveillance enzyme ribonuclease H2 (RNase H2) cause Aicardi-Goutières syndrome (AGS), a pediatric disorder that shares features with the autoimmune disease systemic lupus erythematosus (SLE). Here we determined that heterozygous parents of AGS patients exhibit an intermediate autoimmune phenotype and demonstrated a genetic association between rare RNASEH2 sequence variants and SLE.
View Article and Find Full Text PDFRibonuclease H2 plays an essential role for genome stability as it removes ribonucleotides misincorporated into genomic DNA by replicative polymerases and resolves RNA/DNA hybrids. Biallelic mutations in the genes encoding the three RNase H2 subunits cause Aicardi-Goutières syndrome (AGS), an early-onset inflammatory encephalopathy that phenotypically overlaps with the autoimmune disorder systemic lupus erythematosus. Here we studied the intracellular dynamics of RNase H2 in living cells during DNA replication and in response to DNA damage using confocal time-lapse imaging and fluorescence cross-correlation spectroscopy.
View Article and Find Full Text PDFBrain size is precisely regulated during development and involves coordination of neural progenitor cell proliferation, differentiation, and survival. The adapter protein ShcA transmits signals from receptor tyrosine kinases via MAPK (mitogen-activated protein kinase)/ERK (extracellular signal-regulated kinase) and PI3K (phosphatidylinositol 3-kinase)/Akt signaling pathways. In the CNS, ShcA expression is high during embryonic development but diminishes as cells differentiate and switches to ShcB/Sck/Sli and ShcC/N-Shc/Rai.
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