Long-term outcomes of antenatal corticosteroids treatment in very preterm infants after chorioamnionitis.

PURPOSE: To evaluate the effect of antenatal corticosteroids (AC) therapy on short- and long-term outcomes among very low birth weight preterm infants after histologic chorioamnionitis (HCA). METHODS: We performed a retrospective analysis of 5240 single very low birth weight (VLBW) infants born at 22 + 0 and 33 + 6 weeks of gestation between 2003 and 2007, who registered to the Neonatal Research Network Japan. The effects of AC therapy on mortality, neurodevelopmental outcomes at 3 years of age and neonatal morbidities were analyzed in the groups with or without HCA using logistic regression analysis. RESULTS: In the study subjects, 840 were with HCA, 2734 were without HCA, and 1666 were excluded without data for HCA. AC therapy was significantly associated with decreasing mortality before 3 years of age; [0.52 (0.32-0.86)], [odds ratio (95 % confidence intervals]. There were no differences between the two groups regarding neurodevelopmental outcomes, including cerebral palsy [0.90 (0.41-1.99)], development quotient <70 [0.93 (0.48-1.81)], visual impairment [0.46 (0.04-5.18)], and severe hearing impairment [4.00 (0.30-53.4)] in the group with HCA as well as without HCA. Regarding neonatal morbidities, AC therapy was associated with a lower incidence of respiratory distress syndrome [0.67 (0.50-0.91)], sepsis [0.62 (0.41-0.94)], late-onset adrenal insufficiency [0.62 (0.39-0.98)] and an increased incidence of chronic lung disease [1.62 (1.18-2.24)] in the group with HCA. In the group without HCA, AC therapy was associated with decreasing respiratory distress syndrome [0.60 (0.43-0.84)] and increasing chronic lung disease [1.34 (1.11-1.62)]. CONCLUSION: AC therapy is significantly associated with reduced mortality before 3 years of age in VLBW infants with HCA, but not with neurodevelopmental outcomes, which was same as the results found in infants without HCA. AC therapy is recommended for women with suspected chorioamnionitis, as well as those without chorioamnionitis.

Structure basis for the regulation of glyceraldehyde-3-phosphate dehydrogenase activity via the intrinsically disordered protein CP12.

The reversible formation of a glyceraldehyde-3-phosphate dehydrogenase (GAPDH)-CP12-phosphoribulokinase (PRK) supramolecular complex, identified in oxygenic photosynthetic organisms, provides light-dependent Calvin cycle regulation in a coordinated manner. An intrinsically disordered protein (IDP) CP12 acts as a linker to sequentially bind GAPDH and PRK to downregulate both enzymes. Here, we report the crystal structures of the ternary GAPDH-CP12-NAD and binary GAPDH-NAD complexes from Synechococcus elongates. The GAPDH-CP12 complex structure reveals that the oxidized CP12 becomes partially structured upon GAPDH binding. The C-terminus of CP12 is inserted into the active-site region of GAPDH, resulting in competitive inhibition of GAPDH. This study also provides insight into how the GAPDH-CP12 complex is dissociated by a high NADP(H)/NAD(H) ratio. An unexpected increase in negative charge potential that emerged upon CP12 binding highlights the biological function of CP12 in the sequential assembly of the supramolecular complex.