No abstract

Methionyl-tRNA synthetase (MARS) catalyzes the ligation of methionine to tRNA and is critical for protein biosynthesis. We identified biallelic missense mutations in MARS in a specific form of pediatric pulmonary alveolar proteinosis (PAP), a severe lung disorder that is prevalent on the island of Réunion and the molecular basis of which is unresolved. Mutations were found in 26 individuals from Réunion and nearby islands and in two families from other countries. Functional consequences of the mutated alleles were assessed by growth of wild-type and mutant strains and methionine-incorporation assays in yeast. Enzyme activity was attenuated in a liquid medium without methionine but could be restored by methionine supplementation. In summary, identification of a founder mutation in MARS led to the molecular definition of a specific type of PAP and will enable carrier screening in the affected community and possibly open new treatment opportunities.

We identified SPOCK2 as a new possible candidate susceptibility gene for bronchopulmonary dysplasia. Its lung expression pattern points toward a potential role in alveolarization.

ClinicalTrials.gov-NCT02758119.

BACKGROUND AND OBJECTIVE: Congenital pulmonary malformations (CPM) are mostly recognized on prenatal ultrasound scans. In a minority of cases, they may impair breathing at birth. The factors predictive of neonatal respiratory distress are not well defined, but an understanding of these factors is essential for decisions concerning the need for the delivery to take place in a tertiary care center. The aim of this study was to identify potential predictors of respiratory distress in neonates with CPM. METHODS: We selected cases of prenatal diagnosis of hyperechoic and/or cystic lung lesions from RespiRare, the French prospective multicenter registry for liveborn children with rare respiratory diseases (2008–2013). Prenatal parameters were correlated with neonatal respiratory outcome. RESULTS: Data were analyzed for 89 children, 22 (25%) of whom had abnormal breathing at birth. Severe respiratory distress, requiring oxygen supplementation or ventilatory support, was observed in 12 neonates (13%). Respiratory distress at birth was significantly associated with the following prenatal parameters: mediastinal shift (P = .0003), polyhydramnios (P = .05), ascites (P = .0005), maximum prenatal malformation area (P = .001), and maximum congenital pulmonary malformation volume ratio (CVR) (P = .001). Severe respiratory distress, requiring oxygen at birth, was best predicted by polyhydramnios, ascites, or a CVR >0.84. CONCLUSIONS: CVR >0.84, polyhydramnios, and ascites increased the risk of respiratory complications at birth in fetuses with CPM, and especially of severe respiratory distress, requiring oxygen supplementation or more intensive intervention. In such situations, the delivery should take place in a tertiary care center.

Serious games are educational tools which are more and more used in patient and health professional education. In this article, we discuss three main points that developers and educators need to address during the development of a serious game for health. We first explain how to develop motivating serious games by finding a point where the intrinsic and extrinsic motivations of end users can converge. Then, we propose to identify the features of serious games which enhance their learning effectiveness on the basis of a framework derived from cognitive science and called “the four pillars of learning.” Finally, we discuss issues and solutions related to the evaluation of serious games.

Although serious games designed for asthma education have evolved with advances in technology, results of their evaluation remained similar across studies, with clear improvements in knowledge but little or no change in behaviors and clinical outcomes.

BackgroundIdiopathic eosinophilic pneumonia is extremely rare in children and adults. We present herein the first series describing the specificities of idiopathic chronic (ICEP) and acute (IAEP) eosinophilic pneumonia in children.MethodsWe retrospectively analyzed all cases of ICEP and IAEP in children that were retrieved from French Reference Centers for rare pediatric lung diseases.ResultsFive cases of pediatric ICEP were identified. Corticosteroid or immunosuppressive therapy dramatically improved the outcome in three cases. The remaining two cases had a persistent interstitial pattern with progressive development of cystic airspace lesions. Three cases of IAEP in adolescents were reported, with one requiring four days of extracorporeal membrane oxygenation.ConclusionICEP is a rare disease with a polymorphic clinical presentation in children. We identified patients with persistent interstitial patterns progressing to cystic airspace regions, for which the boundaries with idiopathic interstitial pneumonias are difficult to establish. We therefore propose a specific pediatric definition and classification algorithm. IAEP in children remains an inflammatory reaction of the lung to an acute toxic exposure, mainly tobacco, as in adults. International studies are required to comprehensively assess the various clinical forms of the disease as well as the appropriate therapeutic regimens.