Anxiety levels in parents of asymptomatic neonates and young infants referred for echocardiography.

INTRODUCTION: Previous studies in children with innocent murmurs have shown that parental concern is common. METHODS: We assessed the anxiety levels among parents of asymptomatic neonates or infants up-to 6 weeks referred for cardiologic consultation because of a heart murmur. A six-item short-form of the state scale of the Spielberger State-Trait Anxiety Inventory (STAI) was completed by the parents before and after consultation. RESULTS: The average STAI score decreased from 14.42 ± 4.54 on arrival to 9.69 ± 4.26 after the consultation (p < 0.001). Overall, the parents felt more calm, less tense, less upset, more relaxed, more content and less worried after the consultation (p < 0.001). Multivariable linear regression analysis showed that the STAI score prior to consultation was related to infants age (coefficient ß = - 0.172; P = 0.046) and STAI score post consultation was related to the final diagnosis (ß = 0.312; P < 0.001). CONCLUSION: In conclusion, parents of asymptomatic neonates and young infants with a murmur exhibit moderate levels of anxiety which can be ameliorated after consultation. Parental education in the field is of paramount importance and the role of both paediatric cardiologists as well as primary care physicians is crucial and decisive.

Dynasore impairs VEGFR2 signalling in an endocytosis-independent manner.

VEGFR2 is a critical angiogenic receptor playing a key role in vascular homeostasis. Upon activation by VEGF, VEGFR2 becomes endocytosed. Internalisation of VEGFR2 is facilitated, in part, through clathrin mediated endocytosis (CME), the role of which in VEGFR2 function is debated. Here, we confirm the contribution of CME in VEGFR2 uptake. However, curiously, we find that different approaches of inhibition of CME exert contradictory effects on VEGF signalling; knockdown of clathrin, or of dynamin, or overexpression of dynamin K44A, do not affect VEGF-induced phosphorylation of ERK1/2, while dynasore causes strong inhibition. We resolve this discrepancy by showing that although dynasore inhibits CME of VEGFR2, its inhibitory action in ERK1/2 phosphorylation is not related to attenuation of VEGFR2 endocytosis; it is rather due to an off-target effect of the drug. Dynasore inhibits VEGF-induced calcium release, a signalling event that lies upstream of ERK1/2, which implies that this effect could be responsible, at least in part, for the inhibitory action of the drug on VEGF-to-ERK1/2 signalling. These results raise caution that although dynasore is specific in inhibiting clathrin- and dynamin-mediated endocytosis, it may also exert off-target effects on signalling molecules, hence influencing the interpretation of the role of endocytosis in signalling.

Purine utilization proteins in the Eurotiales: cellular compartmentalization, phylogenetic conservation and divergence.

The purine utilization pathway has been thoroughly characterized in Aspergillus nidulans. We establish here the subcellular distribution of seven key intracellular enzymes, xanthine dehydrogenase (HxA), urate oxidase (UaZ), 5-hydroxy-isourate hydrolase (UaX), 2-oxo-4-hydroxy-4-carboxy ureido imidazoline decarboxylase (UaW), allantoinase (AlX), allantoicase (AaX), ureidoglycolate lyase (UglA), and the fungal-specific α-ketoglutarate Fe(II)-dependent dioxygenase (XanA). HxA, AlX, AaX, UaW and XanA are cytosolic, while UaZ, UaX and UglA are peroxisomal. Peroxisomal localization was confirmed by using appropriate pex mutants. The pathway is largely, but not completely conserved in the Eurotiomycetes, noticeably in some species AaX is substituted by an alternative enzyme of probable bacterial origin. UaZ and the urate-xanthine UapA and UapC transporters, are also localized in specific cells of the conidiophore. We show that metabolic accumulation of uric acid occurring in uaZ null mutations is associated with an increased frequency of appearance of morphologically distinct colony sectors, diminished conidiospore production, UV resistance and an altered response to oxidation stress, which may provide a rationale for the conidiophore-specific localization. The pathway-specific transcription factor UaY is localized in both the cytoplasm and nuclei under non-inducing conditions, but it rapidly accumulates exclusively to the nuclei upon induction by uric acid.