Congenital Zika virus infection as a silent pathology with loss of neurogenic output in the fetal brain

Zika virus (ZIKV) is a flavivirus with teratogenic effects on fetal brain, but the spectrum of ZIKV-induced brain injury is unknown, particularly when ultrasound imaging is normal. In a pregnant pigtail macaque (Macaca nemestrina) model of ZIKV infection, we demonstrate that ZIKV-induced injury to fetal brain is substantial, even in the absence of microcephaly, and may be challenging to detect in a clinical setting. A common and subtle injury pattern was identified, including (i) periventricular T2-hyperintense foci and loss of fetal noncortical brain volume, (ii) injury to the ependymal epithelium with underlying gliosis and (iii) loss of late fetal neuronal progenitor cells in the subventricular zone (temporal cortex) and subgranular zone (dentate gyrus, hippocampus) with dysmorphic granule neuron patterning. Attenuation of fetal neurogenic output demonstrates potentially considerable teratogenic effects of congenital ZIKV infection even without microcephaly. Our findings suggest that all children exposed to ZIKV in utero should receive long-term monitoring for neurocognitive deficits, regardless of head size at birth

Analysis of coulomb interaction using modified particle-particle-particle-mesh method in Monte Carlo simulation

We introduce a particle{particle{particle{mesh (P3M) method modi ed by a simple yet accurate numerical reference force, which solves the ambiguity of the original P3M method by e ectively eliminating double-counting of pair forces inside the short range. The substantial advantages over the original method are con rmed with extensive veri cations. The modi ed P3M method is implemented into an ensemble Monte Carlo (EMC) simulator, MOCA3D, to treat the Coulomb scattering, i.e. carrier-carrier and carrier-impurity scattering. We show that most of the problems in the particle{mesh (PM) based scattering rate approach are solved by the P3M method. The properties of the Coulomb scattering are analyzed by comparison of the proposed and the conventional approaches. One of the important observations is that the introduction of discrete dopants in EMC simulation signi cantly in uences the carrier energy and the device performance. The proposed method can also be applied for the random dopant uctuation (RDF) simulation, in which the accurate treatment of charge granular e ect is required. Furthermore, a 2-D P3M method is developed based on the 3-D approach. The inherent di culty in 2-D simulation, due to the line-charge approximation, can be overcome by a quasi 3-D approach. The application results also show the properties and the shortcomings of the 2-D approach. The validity and the accuracy of the proposed 3-D and 2-D P3M-EMC simulators are veri ed with the low- eld mobility extraction. We believe that the proposed P3M approach both in 3-D and 2-D has improved the applicability of the original P3M method and can be used widely for the calculation of inter-particle forces

Congenital Zika virus infection as a silent pathology with loss of neurogenic output in the fetal brain.

Zika virus (ZIKV) is a flavivirus with teratogenic effects on fetal brain, but the spectrum of ZIKV-induced brain injury is unknown, particularly when ultrasound imaging is normal. In a pregnant pigtail macaque (Macaca nemestrina) model of ZIKV infection, we demonstrate that ZIKV-induced injury to fetal brain is substantial, even in the absence of microcephaly, and may be challenging to detect in a clinical setting. A common and subtle injury pattern was identified, including (i) periventricular T2-hyperintense foci and loss of fetal noncortical brain volume, (ii) injury to the ependymal epithelium with underlying gliosis and (iii) loss of late fetal neuronal progenitor cells in the subventricular zone (temporal cortex) and subgranular zone (dentate gyrus, hippocampus) with dysmorphic granule neuron patterning. Attenuation of fetal neurogenic output demonstrates potentially considerable teratogenic effects of congenital ZIKV infection even without microcephaly. Our findings suggest that all children exposed to ZIKV in utero should receive long-term monitoring for neurocognitive deficits, regardless of head size at birth