Holoprosencephaly

Holoprosencephaly (HPE) is a complex brain malformation resulting from incomplete cleavage of the prosencephalon, occurring between the 18th and the 28th day of gestation and affecting both the forebrain and the face. It is estimated to occur in 1/16,000 live births and 1/250 conceptuses. Three ranges of increasing severity are described: lobar, semi-lobar and alobar HPE. Another milder subtype of HPE called middle interhemispheric variant (MIHF) or syntelencephaly is also reported. In most of the cases, facial anomalies are observed in HPE, like cyclopia, proboscis, median or bilateral cleft lip/palate in severe forms, ocular hypotelorism or solitary median maxillary central incisor in minor forms. These latter midline defects can occur without the cerebral malformations and then are called microforms. Children with HPE have many medical problems: developmental delay and feeding difficulties, epilepsy, instability of temperature, heart rate and respiration. Endocrine disorders like diabetes insipidus, adrenal hypoplasia, hypogonadism, thyroid hypoplasia and growth hormone deficiency are frequent. To date, seven genes have been positively implicated in HPE: Sonic hedgehog (SHH), ZIC2, SIX3, TGIF, PTCH, GLI2 and TDGF1. A molecular diagnosis can be performed by gene sequencing and allele quantification for the four main genes SHH, ZIC2, SIX3 and TGIF. Major rearrangements of the subtelomeres can also be identified by multiplex ligation-dependent probe amplification (MLPA). Nevertheless, in about 70% of cases, the molecular basis of the disease remains unknown, suggesting the existence of several other candidate genes or environmental factors. Consequently, a "multiple-hit hypothesis" of genetic and/or environmental factors (like maternal diabetes) has been proposed to account for the extreme clinical variability. In a practical approach, prenatal diagnosis is based on ultrasound and magnetic resonance imaging (MRI) rather than on molecular diagnosis. Treatment is symptomatic and supportive, and requires a multidisciplinary management. Child outcome depends on the HPE severity and the medical and neurological complications associated. Severely affected children have a very poor prognosis. Mildly affected children may exhibit few symptoms and may live a normal life

Are stirring and sonication pre-dispersion methods equivalent for in vitro toxicology evaluation of SiC and TiC?

The evolution of the particle size distribution and the surface composition of silicon carbide and titanium carbide nanoparticle (NP) dispersions were studied. The pre-dispersions were prepared using two commonly used protocols for dispersion: stirring and sonication. Two dispersants were investigated (water and Pluronic F108 1 %) at two stages: predispersion and during in vitro assays. Our data show that for each tested condition, different time-dependent results for the surface chemical composition as well as size and percentage of the agglomerates and the primary particles are observed. De-agglomeration and successive or simultaneous cleaning-wrapping cycles of the nanomaterial are observed and are related to the dispersion method and the medium as well as to the chemical stability of the NP surface. Biological response during in vitro assessment was also performed for one given pre-dispersion time condition and demonstrates that the preparation method significantly alters the resultsKavli Institute of NanoScienceApplied Science