A novel autoregulatory loop between the Gcn2-Atf4 pathway and (L)-Proline [corrected] metabolism controls stem cell identity.

Increasing evidence indicates that metabolism is implicated in the control of stem cell identity. Here, we demonstrate that embryonic stem cell (ESC) behaviour relies on a feedback loop that involves the non-essential amino acid L-Proline (L-Pro) in the modulation of the Gcn2-Eif2α-Atf4 amino acid starvation response (AAR) pathway that in turn regulates L-Pro biosynthesis. This regulatory loop generates a highly specific intrinsic shortage of L-Pro that restricts proliferation of tightly packed domed-like ESC colonies and safeguards ESC identity. Indeed, alleviation of this nutrient stress condition by exogenously provided L-Pro induces proliferation and modifies the ESC phenotypic and molecular identity towards that of mesenchymal-like, invasive pluripotent stem cells. Either pharmacological inhibition of the prolyl-tRNA synthetase by halofuginone or forced expression of Atf4 antagonises the effects of exogenous L-Pro. Our data provide unprecedented evidence that L-Pro metabolism and the nutrient stress response are functionally integrated to maintain ESC identity.

VATS: first step in the parapneumonic empyema*.

Pneumonia is a common cause of pediatric hospitalization and almost 50% of children hospitalized for pneumonia develops meta pneumonic pleural effusion, most of which resolve spontaneously (1). The meta pneumonic effusion remains a major source of morbidity and mortality in the pediatric population and is a complication on the rise in both the U.S. (2) and Europe (3-6). There is no uniformity of treatment of the meta pneumonic effusion in its early stages and are still questioning some aspects of proper management, remains uncertain and not always shared the operative timing (7). The treatment options are represented, in combination with antibiotic therapy, the thoracentesis (8), the positioning of one or more pleural drainage (9), fibrinolytic therapy (10), the toilet of the pleural cavity by means of video-assisted thoracoscopic surgery (VATS) (11) or "open" with thoracotomy (12) or traditional mini thoracotomy. We report our experience concerning the processing of meta pneumonic effusion, suggesting how the video thoracoscopy may be the treatment of choice in the early stages of the disease.

[A familial strain of amelogenesis imperfecta hypoplastic type with dominant x-linked heredity]. / Su un ceppo familiare di amelogenesi imperfetta del tipo ipoplastico ad ereditarieta X-linked dominante

Hypoplastic amelogenesis imperfecta in members of four generations of a Campanian family is described. The females were affected to a lesser degree. A dominant X-linked mutation was apparently involved. The different forms of amelogenesis imperfecta are described in the light of their anatomical, clinical and radiological pictures and their transmission modalities. Suitable corrective treatment is required to offset the damage to masticatory function, and associated psychological and emotional consequences, especially in female subjects.