Predictors of recurrent wheezing in late preterm infants.

INTRODUCTION: Premature infants have an increased risk of respiratory morbidity, including the development of recurrent wheezing. We sought to determine perinatal factors in late preterm infants associated with an increased risk of recurrent wheezing in the first 3 years of life. METHODS: A retrospective chart review of infants born between 32 and 36 weeks gestational age at a tertiary hospital from 2013 to 2016 was performed. Infants with any co-morbid medical conditions were excluded. Recurrent wheezing was identified by two or more visit diagnoses for reactive airway disease, wheezing-associated respiratory infection, wheezing, or asthma during the first 3 years of life. Those with recurrent wheezing were compared to matched preterm infants who did not develop wheezing. RESULTS: Three hundred and fourteen late preterm infants were included in this study; 210 infants developed recurrent wheezing while 104 did not. Gender, sex, and race were comparable between both groups. Development of wheezing was associated with positive family history of asthma (p = .014), receiving antibiotics during the neonatal period (p < .001), requiring continuous positive airway pressure for <24 h (p = .019), and receiving supplemental oxygen during the newborn period (p = .023). CONCLUSION: This study retrospectively identified risk factors associated with development of wheezing in late preterm infants. Prospective studies are needed to determine whether these factors will predict recurrent wheeze in this patient population.

DNA damage checkpoint activation affects peptidoglycan synthesis and late divisome components in Bacillus subtilis.

During normal DNA replication, all cells encounter damage to their genetic material. As a result, organisms have developed response pathways that provide time for the cell to complete DNA repair before cell division occurs. In Bacillus subtilis, it is well established that the SOS-induced cell division inhibitor YneA blocks cell division after genotoxic stress; however, it remains unclear how YneA enforces the checkpoint. Here, we identify mutations that disrupt YneA activity and mutations that are refractory to the YneA-induced checkpoint. We find that YneA C-terminal truncation mutants and point mutants in or near the LysM peptidoglycan binding domain render YneA incapable of checkpoint enforcement. In addition, we develop a genetic method which isolated mutations in the ftsW gene that completely bypassed checkpoint enforcement while also finding that YneA interacts with late divisome components FtsL, Pbp2b, and Pbp1. Characterization of an FtsW variant resulted in considerably shorter cells during the DNA damage response indicative of hyperactive initiation of cell division and bypass of the YneA-enforced DNA damage checkpoint. With our results, we present a model where YneA inhibits septal cell wall synthesis by binding peptidoglycan and interfering with interaction between late arriving divisome components causing DNA damage checkpoint activation.