Metabolomic and Immunologic Discriminators of MIS-C at Emergency Room Presentation.

Multisystem Inflammatory Syndrome in Childhood (MIS-C) follows SARS-CoV-2 infection and frequently leads to intensive care unit admission. The inability to rapidly discriminate MIS-C from similar febrile illnesses delays treatment and leads to misdiagnosis. To identify diagnostic discriminators at the time of emergency department presentation, we enrolled 104 children who met MIS-C screening criteria, 14 of whom were eventually diagnosed with MIS-C. Before treatment, we collected breath samples for volatiles and peripheral blood for measurement of plasma proteins and immune cell features. Clinical and laboratory features were used as inputs for a machine learning model to determine diagnostic importance. MIS-C was associated with significant changes in breath volatile organic compound (VOC) composition as well as increased plasma levels of secretory phospholipase A2 (PLA2G2A) and lipopolysaccharide binding protein (LBP). In an integrated model of all analytes, the proportion of TCRVß21.3+ non-naive CD4 T cells expressing Ki-67 had a high sensitivity and specificity for MIS-C, with diagnostic accuracy further enhanced by low sodium and high PLA2G2A. We anticipate that accurate diagnosis will become increasingly difficult as MIS-C becomes less common. Clinical validation and application of this diagnostic model may improve outcomes in children presenting with multisystem febrile illnesses.

Moderate prenatal alcohol exposure increases total length of L1-expressing axons in E15.5 mice.

Public health campaigns broadcast the link between heavy alcohol consumption during pregnancy and physical, cognitive, and behavioral birth defects; however, they appear less effective in deterring moderate consumption prevalent in women who are pregnant or of childbearing age. The incidence of mild Fetal Alcohol Spectrum Disorders (FASD) is likely underestimated because the affected individuals lack physical signs such as retarded growth and facial dysmorphology and cognitive/behavioral deficits are not commonly detected until late childhood. Sensory information processing is distorted in FASD, but alcohol's effects on the development of axons that mediate these functions are not widely investigated. We hypothesize that alcohol exposure alters axon growth and guidance contributing to the aberrant connectivity that is a hallmark of FASD. To test this, we administered alcohol to pregnant dams from embryonic day (E) 7.5 to 14.5, during the time that axons which form the major forebrain tracts are growing. We found that moderate alcohol exposure had no effect on body weight of E15.5 embryos, but significantly increased the length of L1+ axons. To investigate a possible cause of increased L1+ axon length, we investigated the number and distribution of corridor cells, one of multiple guidance cues for thalamocortical axons which are involved in sensory processing. Alcohol did not affect corridor cell number or distribution at the time when thalamocortical axons are migrating. Future studies will investigate the function of other guidance cues for thalamocortical axons, as well as lasting consequences of axon misguidance with prenatal alcohol exposure.