Synchondrosis fusion contributes to the progression of postnatal craniofacial dysmorphology in syndromic craniosynostosis.

Syndromic craniosynostosis (CS) patients exhibit early, bony fusion of calvarial sutures and cranial synchondroses, resulting in craniofacial dysmorphology. In this study, we chronologically evaluated skull morphology change after abnormal fusion of the sutures and synchondroses in mouse models of syndromic CS for further understanding of the disease. We found fusion of the inter-sphenoid synchondrosis (ISS) in Apert syndrome model mice (Fgfr2S252W/+ ) around 3 weeks old as seen in Crouzon syndrome model mice (Fgfr2cC342Y/+ ). We then examined ontogenic trajectories of CS mouse models after 3 weeks of age using geometric morphometrics analyses. Antero-ventral growth of the face was affected in Fgfr2S252W/+ and Fgfr2cC342Y/+ mice, while Saethre-Chotzen syndrome model mice (Twist1+/- ) did not show the ISS fusion and exhibited a similar growth pattern to that of control littermates. Further analysis revealed that the coronal suture synostosis in the CS mouse models induces only the brachycephalic phenotype as a shared morphological feature. Although previous studies suggest that the fusion of the facial sutures during neonatal period is associated with midface hypoplasia, the present study suggests that the progressive postnatal fusion of the cranial synchondrosis also contributes to craniofacial dysmorphology in mouse models of syndromic CS. These morphological trajectories increase our understanding of the progression of syndromic CS skull growth.

Pharmaceuticals and Medical Device Agency approval summary: Amenamevir for the treatment of herpes zoster.

In July 2017, Japan's Ministry of Health, Labor and Welfare issued a marketing authorization valid throughout Japan for N-(2,6-dimethylphenyl)-N-(2-{[4-(1,2,4-oxadiazol-3-yl)phenyl]amino}-2-oxoethyl)-1,1-dioxothiane-4-carboxamide (amenamevir) for the first time worldwide. The decision was based on the favorable opinion of the Pharmaceuticals and Medical Device Agency (PMDA) recommending a marketing authorization of amenamevir for treatment of herpes zoster (HZ). Amenamevir has a different action mechanism from previously approved synthetic nucleoside compounds for the treatment of HZ including acyclovir, valacyclovir and famciclovir. The usual adult dose is 400 mg amenamevir p.o. once daily for 7 days. The benefit is its ability to cure HZ as well as preventing postherpetic neuralgia. The most common side-effects are increase of urine N-acetyl-ß-D-glucosaminidase and α1-microglobulin levels. However, based on the detailed evaluation of the submitted clinical studies, there seems to be no serious safety concerns about amenamevir regarding the kidney of both renally normal and impaired patients. The objective of this article is to summarize the scientific review of the application. The detailed scientific assessment report and product information, including the summary of product characteristics, are available on the PMDA website (www.pmda.go.jp/PmdaSearch/iyakuSearch/).

Dynamic and interactive generation of object handling behaviors by a small humanoid robot using a dynamic neural network model.

This study presents experiments on the learning of object handling behaviors by a small humanoid robot using a dynamic neural network model, the recurrent neural network with parametric bias (RNNPB). The first experiment showed that after the robot learned different types of ball handling behaviors using human direct teaching, the robot was able to generate adequate ball handling motor sequences situated to the relative position between the robot's hands and the ball. The same scheme was applied to a block handling learning task where it was shown that the robot can switch among learned different block handling sequences, situated to the ways of interaction by human supporters. Our analysis showed that entrainment of the internal memory structures of the RNNPB through the interactions of the objects and the human supporters are the essential mechanisms for those observed situated behaviors of the robot.