Anti-NEFH monoclonal antibody, clone 2F11

The purpose of our project was to compare the dietary intakes, anthropometric measurements, and perceptions of cardiovascular disease (CVD) risk of young women at risk of developing CVD because of an early family history (EFH) of the disease with women who did not have an early family history (NEFH) of CVD. Data collected from a random sample of 101 healthy women 20 to 29 years of age included family history of CVD, three-day dietary intakes, height, weight, triceps, suprailiac, and thigh skinfold measurements, waist and hip circumferences, percent body fat, and perception of risk of developing CVD. The EFH (N=63) and NEFH (N=38) groups were compared using MANOVA and chi-square. Women in the two groups ate similar amounts of fat and were similar in percent body fat. Mean fat and saturated fatty acid consumption were 34% and 13% of energy intake, respectively. Three-fourths of the women consumed >30% of energy from fat. Mean percent body fat was 26% of body weight. Two-thirds of the EFH women underestimated their risk of developing CVD. We conclude that there is a need for nutrition education programs aimed at reducing CVD risk in young women and these programs need to be directed at reducing womens' fat consumption and their present body fat.

BackgroundAmyotrophic lateral sclerosis (ALS) is a debilitating disease with few treatment options. Progress towards new therapies requires validated disease biomarkers, but there is no consensus on which fluid-based measures are most informative.MethodsThis study analyzed microarray data derived from blood samples of patients with ALS (n=396), ALS mimic diseases (n=75), and healthy controls (n=645). Goals were to provide in-depth analysis of differentially expressed genes (DEGs), characterize patient-to-patient heterogeneity, and identify candidate biomarkers.ResultsWe identified 752 ALS-increased and 764 ALS-decreased DEGs (FDR<0.10 with>10% expression change). Gene expression shifts in ALS blood broadly resembled acute high altitude stress responses. ALS-increased DEGs had high exosome expression, were neutrophil-specific, associated with translation, and overlapped significantly with genes near ALS susceptibility loci (e.g., IFRD1, TBK1, CREB5). ALS-decreased DEGs, in contrast, had low exosome expression, were erythroid lineage-specific, and associated with anemia and blood disorders. Genes encoding neurofilament proteins (NEFH, NEFL) had poor diagnostic accuracy (50-53%). However, support vector machines distinguished ALS patients from ALS mimics and controls with 87% accuracy (sensitivity: 86%, specificity: 87%). Expression profiles were heterogeneous among patients and we identified two subgroups: (i) patients with higher expression of IL6R and myeloid lineage-specific genes and (ii) patients with higher expression of IL23A and lymphoid-specific genes. The gene encoding copper chaperone for superoxide dismutase (CCS) was most strongly associated with survival (HR=0.77; P=1.84e-05) and other survival-associated genes were linked to mitochondrial respiration. We identify a 61 gene signature that significantly improves survival prediction when added to Cox proportional hazard models with baseline clinical data (i.e., age at onset, site of onset and sex). Predicted median survival differed 2-fold between patients with favorable and risk-associated gene expression signatures.ConclusionsPeripheral blood analysis informs our understanding of ALS disease mechanisms and genetic association signals. Our findings are consistent with low-grade neutrophilia and hypoxia as ALS phenotypes, with heterogeneity among patients partly driven by differences in myeloid and lymphoid cell abundance. Biomarkers identified in this study require further validation but may provide new tools for research and clinical practice.