LIN28A/B are RNA binding proteins implicated by genetic association studies in human growth and glucose metabolism. Mice with ectopic over-expression of Lin28a have shown related phenotypes. Here we describe the first comprehensive analysis of the physiologic consequences of Lin28a and Lin28b deficiency in knockout (KO) mice. Lin28a/b-deficiency led to dwarfism starting at different ages, and compound gene deletions showed a cumulative dosage effect on organismal growth. Conditional gene deletion at specific developmental stages revealed that fetal but neither neonatal nor adult deficiency resulted in growth defects and aberrations in glucose metabolism. Tissue-specific KO mice implicated skeletal muscle-deficiency in the abnormal programming of adult growth and metabolism. The effects of Lin28b KO can be rescued by Tsc1 haplo-insufficiency in skeletal muscles. Our data implicate fetal expression of Lin28a/b in the regulation of life-long effects on metabolism and growth, and demonstrate that fetal Lin28b acts at least in part via mTORC1 signaling.

No abstract

Purpose To identify characteristics that predict successful telephone follow-up with parents of infants with severe bronchiolitis. Methods We analyzed data from a 17-center, prospective cohort study of infants (age <1 year) hospitalized with bronchiolitis during three consecutive fall/winter seasons. Participant contact information and clinical data were collected during the index hospitalization. Parents were called at 6-month intervals (based on the child’s age) after discharge to assess respiratory problems. The primary outcome was age 12-month telephone interview status. Participants were classified as unreachable after 28 days of unsuccessful attempts. Results 798 of 916 children (87%) completed the age 12-month telephone interview. In unadjusted analyses, factors associated with successful follow-up included: private health insurance, annual household income ≥$60,000, and residing in the Northeast, Midwest, or West. Follow-up was less common among non-Hispanic blacks, Hispanics, and households with ≥3 children. In multivariable analyses, follow-up was more likely among parents of females, and, compared to the South, in the Northeast and Midwest (all P<0.05). Compared to non-Hispanic whites, non-Hispanic blacks and Hispanics remained less likely to complete the interview as did households with ≥3 children (all P<0.05). Conclusion Socio-demographic and geographic factors predict successful telephone follow-up, even among parents of infants with severe illness.