Undernutrition is a risk factor for under 5 mortality and is also postulated to be a risk factor for mortality in older children and adults with sickle cell anemia. We tested the hypothesis that underweight (weight-for-age z-score <-1) is associated with mortality in children aged 5-12 years with sickle cell anemia. We performed a secondary analysis of participants in the Primary Prevention of Stroke in Children with Sickle Cell Disease in Nigeria trial, a double-blind, parallel-group randomized controlled trial for low-dose (n=109) or moderate-dose (n=111) hydroxyurea in children with abnormal transcranial Doppler velocities and a comparison group (n=211) of participants with non-elevated transcranial Doppler velocities in northern Nigeria (NCT02560935). Nutritional status was classified as underweight (weight-for-age z-score), stunting (height-for-age z-score), and wasting (body mass index z-score) using the World Health Organization growth reference. The mean weight-for-age z-score was lower in children who died during the study than in those who survived (-2.6 vs. -2.1, p=0.016). Otherwise, the baseline characteristics of children who died during the study were not significantly different from those who survived. A pooled analysis of participants demonstrated that a lower weight-for-age z-score was associated with an increased hazard of death (HR=0.580, p=0.004, 95%CI 0.399-0.843). Underweight participants (weight-for-age z-score <-1) had a greater probability of death during follow-up than those not underweight (p=0.043). Underweight status in school-aged children with sickle cell anemia is a previously unrecognized risk factor for early mortality in Nigeria and can be easily applied to screen children at risk for death.
The function of the frizzled (fz) locus is required to coordinate the cytoskeletons of pupal epidermal cells so that a parallel array of cuticular hairs and bristles is produced. We report here the molecular cloning and characterization of the fz locus. The locus is very large. Mutations that inactivate the gene are spread over 100 kb of genomic DNA. The major mRNA product of the gene is a 4-kb RNA that is encoded by 5 exons spread over more than 90 kb of genomic DNA. Conceptual translation of this mRNA indicates that it encodes an integral membrane protein that is likely to contain both extracellular and cytoplasmic domains.
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