Developmental Consequences of Prenatal Telbivudine Exposure during the Third Trimester.

Hepatitis B virus (HBV) infection is a global health issue. Mother-to-child transmission (MTCT) is the most prominent route for chronic HBV infection in Asian countries.1 Although standard immunoprophylaxis has been effective in preventing MTCT, a significantly higher rate of MTCT has been observed among mothers with high levels of viremia.2 Tenofovir disoproxil, telbivudine (LdT), and lamivudine, used in third trimester, have been shown to significantly reduce MTCT of HBV for highly viremic mothers.3 Although the efficacy and short-term safety of LdT in preventing MTCT have been demonstrated in several large cohort studies in recent years, fewer data exist on the safety assessment of infants' neurocognitive development after fetal exposure to LdT.4-6 Therefore, we conducted a prospective cohort study to investigate the effect of LdT on infants' neurocognitive development.

Enhanced expression of CGRP in rat trigeminal ganglion neurons during cell and organ culture.

The sensory innervation of intracranial vessels originates in the trigeminal ganglion with calcitonin gene-related peptide (CGRP), substance P (SP) and pituitary adenylate cyclase activating peptide (PACAP) as frequent neuronal messengers. The present study was designed to study the expression of these neuropeptides (a) in primary culture of adult rat trigeminal ganglion neuronal cells and (b) in organ culture of sections of the trigeminal ganglion. In cell culture, axons grow in the peripheral direction for up to 48 h. Immunocytochemistry revealed that the cell bodies showed increased expression of CGRP at 24 h and SP at 24-48 h (p<0.05), whereas cell culture did not increase the expression of PACAP at 24 h (p>0.05), but at 48 h (p<0.05). A significant elevation of CGRP mRNA was seen at 12 h, i.e. before the increased CGRP immunoreaction was observed. In organ culture of sections of trigeminal ganglia, the number of CGRP immunoreactive (-ir) cells and the mRNA expression were significantly increased at 24 and 48 h of incubation as compared to control (p<0.05), while the number of SP-ir cells was not altered (p>0.05). In conclusion, neurons of rat trigeminal ganglia alter their expression of neuropeptides during cell and organ culture differently, but it is mainly the CGRP system that is up-regulated. We have compared two methods for future studies of underlying molecular mechanisms responsible for regulation of neuropeptide expression in the trigeminal system.

Corrigendum: Fluidic Logic Used in a Systems Approach to Enable Integrated Single-Cell Functional Analysis.

[This corrects the article on p. 70 in vol. 4, PMID: 27709111.].

Fluidic Logic Used in a Systems Approach to Enable Integrated Single-Cell Functional Analysis.

The study of single cells has evolved over the past several years to include expression and genomic analysis of an increasing number of single cells. Several studies have demonstrated wide spread variation and heterogeneity within cell populations of similar phenotype. While the characterization of these populations will likely set the foundation for our understanding of genomic- and expression-based diversity, it will not be able to link the functional differences of a single cell to its underlying genomic structure and activity. Currently, it is difficult to perturb single cells in a controlled environment, monitor and measure the response due to perturbation, and link these response measurements to downstream genomic and transcriptomic analysis. In order to address this challenge, we developed a platform to integrate and miniaturize many of the experimental steps required to study single-cell function. The heart of this platform is an elastomer-based integrated fluidic circuit that uses fluidic logic to select and sequester specific single cells based on a phenotypic trait for downstream experimentation. Experiments with sequestered cells that have been performed include on-chip culture, exposure to various stimulants, and post-exposure image-based response analysis, followed by preparation of the mRNA transcriptome for massively parallel sequencing analysis. The flexible system embodies experimental design and execution that enable routine functional studies of single cells.