👤 Eduardo Z Romo

Pilocytic astrocytomas (PAs) are benign grade 1 gliomas according to the World Health Organization (WHO). They are common in children but rare in adults in whom they may have a worse prognosis. Pediatric PAs are usually associated with dysregulation of the mitogen-activated protein kinase (MAPK) pathway, often involving BRAF alterations such as the KIAA1549::BRAF (K-B) fusion or V600E mutation. We investigated the molecular characteristics of adult PA using gene-targeted next-generation sequencing and specific gene tests, including for K-B fusion, TERT promoter, and FGFR1 hotspot mutations. The most frequent molecular alterations detected involved the MAPK pathway, particularly affecting BRAF and NF1 genes (55%). The prevalence of the K-B fusion (>40%) was higher than previously reported, likely due to challenges in detecting it. We identified molecular alterations in some cases that raised the differential diagnosis of other tumor types, revealing limitations in the 2021 WHO classification for adult PA. After removing other diagnostic types that may mimic PA histology, no adult patients with a diagnosis of PA and K-B fusion died after more than 10 years of mean follow-up. These findings suggest that, similar to pediatric cases, PA in adults may be driven by a single molecular hit, where the K-B fusion is not related to poor outcome. Show less

Small-quantity lipid-based nutrient supplements (SQ-LNS) during pregnancy and postnatally were previously shown to improve high-density lipoprotein (HDL) cholesterol efflux capacity (CEC) and length in the children of supplemented mothers at 18 mo of age in the International Lipid-Based Nutrient Supplements (iLiNS) DYAD trial in Ghana. However, the effects of SQ-LNS on maternal HDL functionality during pregnancy are unknown. The goal of this cross-sectional, secondary outcome analysis was to compare HDL function in mothers supplemented with SQ-LNS vs. iron and folic acid (IFA) during gestation. HDL CEC and the activities of 3 HDL-associated enzymes were analyzed in archived plasma samples ( There were no statistically significant differences in HDL CEC, plasma lecithin-cholesterol acyltransferase (LCAT) activity, cholesteryl ester transfer protein (CETP) activity, or phospholipid transfer protein (PLTP) activity between mothers supplemented with SQ-LNS compared with IFA control, and no statistically significant relationships between maternal HDL function and childbirth outcomes. LCAT activity was negatively correlated with plasma AGP (R = -0.19, Mothers in Ghana supplemented with SQ-LNS compared with IFA during gestation did not have measurable differences in HDL functionality, and maternal HDL function was not associated with childbirth outcomes. However, seasonal factors and markers of inflammation were associated with HDL function, indicating that these factors had a stronger influence on HDL functionality than SQ-LNS supplementation during pregnancy. The study was registered as NCT00970866. https://clinicaltrials.gov/study/NCT00970866. Show less

High-density lipoprotein (HDL) particles, long known for their critical role in the prevention of cardiovascular disease (CVD), were recently identified to carry a wide array of glycosylated proteins, and the importance of this glycosylation in the structure, function and metabolism of HDL are starting to emerge. Early studies have demonstrated differential glycosylation of HDL-associated proteins in various pathological states, which may be key to understanding their etiological role in these diseases and may be important for diagnostic development. Given the vast array and specificity of glycosylation pathways, the study of HDL-associated glycosylation has the potential to uncover novel mechanisms and biomarkers of CVD. To date, no large studies examining the relationships between HDL glycosylation profiles and cardiovascular outcomes have been performed. However, small pilot studies provide promising preliminary evidence that such a relationship may exist. In this review article we discuss the current state of the evidence on the glycosylation of HDL-associated proteins, the potential for HDL glycosylation profiling in CVD diagnostics, how glycosylation affects HDL function, and the potential for modifying the glycosylation of HDL-associated proteins to confer therapeutic value. Show less