Ferroptosis of Microglia in Aging Human White Matter Injury.

OBJECTIVE: Because the role of white matter (WM) degenerating microglia (DM) in remyelination failure is unclear, we sought to define the core features of this novel population of aging human microglia. METHODS: We analyzed postmortem human brain tissue to define a population of DM in aging WM lesions. We used immunofluorescence staining and gene expression analysis to investigate molecular mechanisms related to the degeneration of DM. RESULTS: We found that DM, which accumulated myelin debris were selectively enriched in the iron-binding protein light chain ferritin, and accumulated PLIN2-labeled lipid droplets. DM displayed lipid peroxidation injury and enhanced expression for TOM20, a mitochondrial translocase, and a sensor of oxidative stress. DM also displayed enhanced expression of the DNA fragmentation marker phospho-histone H2A.X. We identified a unique set of ferroptosis-related genes involving iron-mediated lipid dysmetabolism and oxidative stress that were preferentially expressed in WM injury relative to gray matter neurodegeneration. INTERPRETATION: Ferroptosis appears to be a major mechanism of WM injury in Alzheimer's disease and vascular dementia. WM DM are a novel therapeutic target to potentially reduce the impact of WM injury and myelin loss on the progression of cognitive impairment. ANN NEUROL 2023;94:1048-1066.

Childhood Obesity and Breastfeeding Rates in Pennsylvania Counties-Spatial Analysis of the Lactation Support Landscape.

Childhood obesity is a global public health issue. As the prevalence of childhood obesity continues to rise, identification of potential interventions by public health policy makers, and health care providers is imperative. Breastfeeding, the most optimal method of infant feeding, has been demonstrated to protect against childhood obesity. Lactation support providers (LSPs) play a key role in providing education, care, and support to families considering a feeding choice. Access to professional lactation care increases breastfeeding initiation, exclusivity, and duration rates, regardless of the credential that the LSP holds. The aims of the current study were to examine the relationship between childhood obesity and breastfeeding rates in Pennsylvania (PA) counties; to examine the relationship between geographic access to professional LSPs in PA counties and breastfeeding rates; and to examine the relationship between geographic access to professional LSPs and childhood obesity in PA counties. Data were collected on 617 professional LSPs in 67 PA counties. There are 608 Certified Lactation Counselors (CLCs) and 144 International Board Certified Lactation Consultants (IBCLCs) in PA. County-level breastfeeding rates, childhood obesity rates, and the number of CLCs and IBCLCs were tested for significance at the p < 0.01 level using a two-tailed significance test and bivariate Pearson's correlation. The results show a significant, inverse relationship between breastfeeding rates and childhood obesity prevalence at the county level, p < 0.01. There is also a significant, inverse relationship between the number of CLCs and the number of all professional LSPs and childhood obesity rates at the county level, p < 0.01. Thus, the availability of breastfeeding support is significantly related to breastfeeding rates and inversely related to childhood obesity rates across Pennsylvania.