Phenotypes of Bronchopulmonary Dysplasia.

Bronchopulmonary dysplasia (BPD) is the most common chronic morbidity in preterm infants. In the absence of effective interventions, BPD is currently a major therapeutic challenge. Several risk factors are known for this multifactorial disease that results in disrupted lung development. Inflammation plays an important role and leads to persistent airway and pulmonary vascular disease. Since corticosteroids are potent anti-inflammatory agents, postnatal corticosteroids have been used widely for BPD prevention and treatment. However, the clinical responses vary to a great degree across individuals, and steroid-related complications remain major concerns. Emerging studies on the molecular mechanism of lung alveolarization during inflammatory stress will elucidate the complicated pathway and help discover novel therapeutic targets. Moreover, with the advances in metabolomics, there are new opportunities to identify biomarkers for early diagnosis and prognosis prediction of BPD. Pharmacometabolomics is another novel field aiming to identify the metabolomic changes before and after a specific drug treatment. Through this "metabolic signature," a more precise treatment may be developed, thereby avoiding unnecessary drug exposure in non-responders. In the future, more clinical, genetic, and translational studies would be required to improve the classification of BPD phenotypes and achieve individualized care to enhance the respiratory outcomes in preterm infants.

Morbidity and mortality of very low birth weight infants in Taiwan-Changes in 15 years: A population based study.

BACKGROUND/PURPOSE: Very low birth weight (VLBW) infants account for over 50% of perinatal deaths in Taiwan. This study aimed to identify changes in parental characteristics, perinatal conditions, mortality, and major neonatal morbidities for VLBW infants in Taiwan, and to highlight the challenges faced by patients, families, and caregivers. METHODS: We conducted a retrospective cohort study to investigate the mortality and morbidity of VLBW infants registered in the Taiwan Premature Infant Follow-up Network from 1997 through 2011. The exclusion criteria included congenital anomalies and chromosome anomalies. Continuous data was represented as mean ± SD, and changes over time in the variables were tested using one-way analysis of variance, with p < 0.05 considered statistically significant. RESULTS: A total of 13,159 VLBW infants were enrolled. We found significant increases over time in the parental age and educational level, in vitro fertilization, first livebirth, multiple births, maternal transfer, cesarean section, and complete antenatal steroid use. Apgar scores at 1 minute and 5 minutes after birth increased, and the intubation rate decreased gradually. Decreasing mortality over time for each successive period was demonstrated. Incidence of some morbidities increased, such as respiratory distress syndrome and patent ductus arteriosus; in contrast, incidence of others decreased, such as sepsis, necrotizing enterocolitis, intraventricular hemorrhage, and chronic lung disease. However, retinopathy of prematurity (ROP) incidence remained constant. CONCLUSION: Although the mortality and most of the morbidity of VLBW infants improved over time, the incidence of ROP remained constant. This requires us to further evaluate our strategy for preventing ROP in the future.

Enhanced expression of beta 3-galactosyltransferase 5 activity is sufficient to induce in vivo synthesis of extended type 1 chains on lactosylceramides of selected human colonic carcinoma cell lines.

In general, an elevated expression of beta 3-galactosyltransferase (beta 3GalT) activity contributed by beta 3GalT5 correlates well with increased biosynthesis and expression of type 1 chain (Gal beta 1-3GlcNAc beta 1-) derivatives such as Lewis A and sialyl Lewis A, which are mostly recognized as terminal epitopes and not further extended. Most known beta 3-N-acetylglucosaminyltransferases show a higher activity toward extending type 2 chain (Gal beta 1-4GlcNAc beta 1-), and an over-expression of beta 3GalT5 could suppress the formation of the type 2 chain poly-N-acetyllactosaminoglycans. The potential of extending instead the predominant type 1 chain termini synthesized under such circumstances was, however, not investigated, partly due to technical difficulty in unambiguous identification of extended type 1 chains. Using an advanced mass spectrometry-based glycomic mapping and glycan sequencing approach, we show here that type 1 chains carried on the lacto-series glycosphingolipids of colonic carcinoma cells can be extended when the endogenous beta 3GalT activity relative to competing beta 4GalT activity, as defined against a common GlcNAc beta 1-3Gal beta 1-4Glc acceptor, is sufficiently high, as found in Colo205 and SW1116, but not in DLD-1 cells. In support of this positive correlation, the lacto-series glycosphingolipids isolated from stably transfected DLD-1 clones over-expressing beta 3GalT5 were shown to comprise fucosylated dimeric type 1 chains, whereas a mock transfectant and the DLD-1 parent carried only fucosylated dimeric type 2 chains on their lactosylceramides. It suggests that while the natural expression of extended type 1 chain is likely to be determined by many contributing factors including the relative amounts of competing glycosyltransferases and the UDP-Gal level, the enhanced expression of beta 3GalT5 is sufficient to promote in vivo extension of type 1 chains by furnishing a significantly higher amount of type 1 chain precursors relative to competing type 2 chains.

Risk Factors for Extubation Failure in Extremely Low Birth Weight Infants.

BACKGROUND: Although antenatal steroids and early use nasal continuous positive airway pressure (NCPAP) have significantly improved outcomes of neonatal respiratory distress syndrome, intubation with ventilator support is still commonly required in extremely low birth weight (ELBW) infants. The optimal timing of extubation in ELBW infants remains unclear. METHODS: We retrospectively analyzed all ELBW preterm infants who were admitted to our neonatal intensive care unit (NICU) from January 2009 to December 2013. Demographic, ventilation, and arterial blood gas analysis results prior to and 2 hours after extubation were collected. Extubation failure was defined as reintubation due to deterioration of respiratory condition within 7 days after extubation. Risk factors for extubation failure were analyzed. RESULTS: In total, 173 ELBW infants were born and admitted to our NICU during these 5 years. Among these 173 infants, 77 (44.5%) used NCPAP only during their hospitalization (20 diagnosed with chronic lung disease (CLD), 25.9%). Among the 95 patients that required intubation, 27 patients expired so extubation was not attempted. Sixteen of 68 (23.5%) survival cases required reintubation within 7 days after extubation. We found that gestational age, birth body weight, and sex ratio did not differ between the successful extubation group and the failed extubation group. Univariate analysis showed that the failed extubation group had a lower arterial pH right before and 2 hours after extubation, with a lower bicarbonate level after extubation. Further multivariate logistic regression analysis revealed an association between poor acid-base homeostasis 2 hours after extubation (pH < 7.3 and HCO3 < 18 mM/L) and extubation failure (odds ratio 4.56 and 6.187 and 95% confidence interval: 1.263∼16.462 and 1.68∼22.791, respectively). CONCLUSION: This study shows that nearly half of ELBW infants do not require intubation. Among ELBW infants who require invasive ventilator support, those who have lower postextubation arterial pH and bicarbonate levels are at high risk of extubation failure.

I branching formation in erythroid differentiation is regulated by transcription factor C/EBPalpha.

The histo-blood group i and I antigens have been characterized as straight and branched repeats of N-acetyllactosamine, respectively, and the conversion of the straight-chain i to the branched-chain I structure on red cells is regulated to occur after birth. It has been demonstrated that the human I locus expresses 3 IGnT transcripts, IGnTA, IGnTB, and IGnTC, and that the last of these is responsible for the I branching formation on red cells. In the present investigation, the K-562 cell line was used as a model to show that the i-to-I transition in erythroid differentiation is determined by the transcription factor CCAAT/enhancer binding protein alpha (C/EBPalpha), which enhances transcription of the IGnTC gene, consequently leading to formation of the I antigen. Further investigation suggested that C/EBPalpha IGnTC-activation activity is modulated at a posttranslational level, and that the phosphorylation status of C/EBPalpha may have a crucial effect. Results from studies using adult and cord erythropoietic cells agreed with those derived using the K-562 cell model, with lentiviral expression of C/EBPalpha in CD34(+) hemopoietic cells demonstrating the determining role of C/EBPalpha in the induction of the IGnTC gene as well as in I antigen expression.