Pulmonary hypertension (PH) contributes to high mortality in congenital diaphragmatic hernia (CDH). A better understanding of the regulatory mechanisms underlying the pathology in CDH might allow the identification of prognostic biomarkers and potential therapeutic targets. We report the results from an expression profiling of circulating microRNAs (miRNAs) in direct post-pulmonary blood flow of 18 CDH newborns. Seven miRNAs differentially expressed in children that either died or developed chronic lung disease (CLD) up to 28 days after birth, compared to those who survived without developing CLD during this period, were identified. Target gene and pathway analyses indicate that these miRNAs functions include regulation of the cell cycle, inflammation and morphogenesis, by targeting molecules responsive to growth factors, cytokines and cellular stressors. Furthermore, we identified hub molecules by constructing a protein-protein interaction network of shared targets, and ranked the relative importance of the identified miRNAs. Our results suggest that dysregulations in miRNAs let-7b-5p, -7c-5p, miR-1307-3p, -185-3p, -8084, -331-3p and -210-3p may be detrimental for the development and function of the lungs and pulmonary vasculature, compromise cardiac function and contribute to the development of CLD in CDH. Further investigation of the biomarker and therapeutic potential of these circulating miRNAs is encouraged.
Streptococcus pneumoniae is one of the major pathogens in invasive diseases in children worldwide. The implementation of national vaccine programs has led to a significant reduction in most circulating pathogenic serotypes. Because of genetic shifts and replacements in the S. pneumoniae population, rare and nonvaccine serotypes have increased in prevalence. We report a case of a 12-month-old girl with Down syndrome and congenital heart disease, suffering from a fulminant pneumococcal meningoencephalitis caused by the nonvaccine serotype 23A. This nonvaccine serotype is an example of the increasing incidence in children with invasive pneumococcal disease (IPD) and illustrates the need for pneumococcal vaccines with broader coverage. Cranial computed tomography (CCT) findings of the patient revealed unusual and extended lesions with bi-hemispheric infarctions and cerebritis, with subsequent widespread intraparenchymal hemorrhage.
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