The 2016 Singapore Zika virus outbreak did not cause a surge in Guillain-Barré syndrome.

Although individuals with Zika virus (ZIKV) antibodies were reported in Malaya in mid-1950s, entomological and human surveillance in Singapore did not identify autochthonous transmission until the outbreak of August-November, 2016. A total of 455 cases from 15 separate clusters were identified. We asked if this ZIKV outbreak increased the incidence of Guillain-Barré syndrome (GBS) and aimed to characterize these cases. Eleven GBS cases, consecutively enrolled into our prospective GBS database from onset to 4 weeks after outbreak, and six controls, comprising three GBS patients enrolled before outbreak and three non-GBS patients, were examined for evidence of recent ZIKV infection. We performed serum, urine ZIKV RT-PCR, ZIKV serology, and virus neutralization assays, accounting for cross-reaction and co-infection with dengue (DENV). We found five GBS cases with only serological evidence of recent ZIKV infection (including one ZIKV-DENV co-infection). A temporal relationship with ZIKV outbreak was unlikely as two cases were GBS controls enrolled 3 months before outbreak. None reported symptoms of ZIKV infection. In addition, compared to last 10 years the national number of GBS hospitalizations did not increase during and immediately after outbreak. We conclude the 2016 Singapore ZIKV outbreak did not cause a change in GBS epidemiology.

BMP-binding protein twisted gastrulation is required in mammary gland epithelium for normal ductal elongation and myoepithelial compartmentalization.

Bone morphogenetic proteins (BMPs) are involved in embryonic mammary gland (MG) development and can be dysregulated in breast cancer. However, the role BMPs play in the postnatal MG remains virtually unknown. BMPs are potent morphogens that are involved in cell fate determination, proliferation, apoptosis and adult tissue homeostasis. Twisted gastrulation (TWSG1) is a secreted BMP binding protein that modulates BMP ligand availability in the extracellular space. Here we investigate the consequences of TWSG1 deletion on development of the postnatal MG. At puberty, Twsg1 is expressed in the myoepithelium and in a subset of body cells of the terminal end buds. In the mature duct, Twsg1 expression is primarily restricted to the myoepithelial layer. Global deletion of Twsg1 leads to a delay in ductal elongation, reduced secondary branching, enlarged terminal end buds, and occluded lumens. This is associated with an increase in luminal epithelial cell number and a decrease in apoptosis. In the MG, pSMAD1/5/8 level and the expression of BMP target genes are reduced, consistent with a decrease in BMP signaling. GATA-3, which is required for luminal identity, is reduced in Twsg1(-/-) MGs, which may explain why K14 positive cells, which are normally restricted to the myoepithelial layer, are found within the luminal compartment and shed into the lumen. In summary, regulation of BMP signaling by TWSG1 is required for normal ductal elongation, branching of the ductal tree, lumen formation, and myoepithelial compartmentalization in the postnatal MG.