Guideline for Care of Patients with the Diagnoses of Craniosynostosis: Working Group on Craniosynostosis

This guideline for care of children with craniosynostosis was developed by a national working group with representatives of 11 matrix societies of specialties and the national patients' society. All medical aspects of care for nonsyndromic and syndromic craniosynostosis are included, as well as the social and psychologic impact for the patient and their parents. Managerial aspects are incorporated as well, such as organizing a timely referral to the craniofacial center, requirements for a dedicated craniofacial center, and centralization of this specialized care. The conclusions and recommendations within this document are founded on the available literature, with a grading of the level of evidence, thereby highlighting the areas of care that are in need of high-quality research. The development of this guideline was made possible by an educational grant of the Dutch Order of Medical Specialists. The development of this guideline was supported by an educational grant of the Dutch Order of Medical Specialists

Metabolic profile and safety of piperlongumine

Piperlongumine (PPL), a natural plant product, has been extensively studied in cancer treatment going up on clinical trials. Since the first report related to its use on cancer research (in 2011) around 80 papers have been published in less than 10 years, but a gap still remaining. There are no metabolism studies of PPL in human organism. For the lack of a better view, here, the CYP450 in vitro oxidation of PPL was described for the first time. In addition, the enzymatic kinetic data, the predicted in vivo parameters, the produced metabolites, the phenotyping study and possible piperlongumine-drug interactions in vivo is presented

External craniofacial osteodistraction in complex craniosynostoses

The use of distraction osteogenesis is the first option in the treatment of craniofacial hypoplasia. Both internal craniofacial distractor devices (ICDD) and external craniofacial distractor devices (ECDD) can improve visual and respiratory functions in patients with craniofacial synostosis significantly. They also improve the cosmetic outcome

Is signaling specificity encoded in arrestin conformation?

The visual/{beta}-arrestins perform remarkably diverse roles in cells. Possessing the capacity to detect and bind hundreds of different activated GPCRs, they are integral to the control of GPCR desensitization, internalization and intracellular trafficking. At the same time, they are able to bind and localize dozens of cargo proteins, including signaling pathway intermediates that affect the tonic level of pathway activity and in some cases confer GPCR-dependent regulation. A fundamental question in biology is how proteins like arrestins can achieve the conformational flexibility necessary to interact with so many different partners while maintaining the specificity necessary for fidelity in signal transduction. Recent data, both from static structures of arrestins in their basal and ‘activated’ conformations, and dynamic resonance energy transfer measurements, have begun to provide answers. Crystallographic and mutagenesis data indicate that the conformational shifts occurring upon receptor engagement are determined by contact between the arrestin globular domains and a relatively few residues within the GPCR intracellular loops. These contacts, in turn, impose receptor-specific arrestin conformations that influence the avidity with which it binds the receptor and its ability to engage certain downstream partners. Differences in ligand structure are likewise encoded in receptor conformation and transmitted to the arrestin, providing the physical basis for ligand ‘bias’. Resonance energy transfer data also indicate that arrestins maintain their ‘active’ conformation for a period of time after letting go of the receptor, raising the possibility that arrestins, like heterotrimeric G proteins, might be activated catalytically