Nail lacquer films’ surface energies and in vitro water-resistance and adhesion do not predict their in vivo residence

The in vivo residence of nail lacquers (which are ideal topical drug carriers for the treatment of nail diseases) determines their frequency of application, and is thereby expected to influence patient adherence and success of treatment. Thus in vitro measurements to indicate lacquers’ in vivo residence are routinely conducted during formulation development. However the literature on in vitro-in vivo correlations is severely limited. Thus, the aim of the work discussed in this paper was to investigate correlations between in vivo residence and in vitro film resistance to water, in vitro film adhesion and surface energy of lacquer films. In vivo measurements were conducted on fingernails in six volunteers. Seven commercially available nail lacquers were tested in commonly-used measurements. Correlations between in vivo residence and in vitro water resistance and adhesion were found to be extremely poor. The surface energies of the lacquer films (which were between 33 and 39 mJ/m2) were also not predictive of in vivo residence. High density polyethylene (HDPE) sheet – whose surface energy was determined to be similar to that of the human nailplate – was found to be a suitable model for the nailplate (when investigating surface energy) and was used in a number of experiments

Dosage Changes of a Segment at 17p13.1 Lead to Intellectual Disability and Microcephaly as a Result of Complex Genetic Interaction of Multiple Genes

The 17p13.1 microdeletion syndrome is a recently described genomic disorder with a core clinical phenotype of intellectual disability, poor to absent speech, dysmorphic features, and a constellation of more variable clinical features, most prominently microcephaly. We identified five subjects with copy-number variants (CNVs) on 17p13.1 for whom we performed detailed clinical and molecular studies. Breakpoint mapping and retrospective analysis of published cases refined the smallest region of overlap (SRO) for microcephaly to a genomic interval containing nine genes. Dissection of this phenotype in zebrafish embryos revealed a complex genetic architecture: dosage perturbation of four genes (ASGR1, ACADVL, DVL2, and GABARAP) impeded neurodevelopment and decreased dosage of the same loci caused a reduced mitotic index in vitro. Moreover, epistatic analyses in vivo showed that dosage perturbations of discrete gene pairings induce microcephaly. Taken together, these studies support a model in which concomitant dosage perturbation of multiple genes within the CNV drive the microcephaly and possibly other neurodevelopmental phenotypes associated with rearrangements in the 17p13.1 SRO