GDF15 linked to maternal risk of nausea and vomiting during pregnancy

GDF15, a hormone acting on the brainstem, has been implicated in the nausea and vomiting of pregnancy (NVP) including its most severe form, Hyperemesis Gravidarum (HG), but a full mechanistic understanding is lacking [1-4]. Here we report that fetal production of GDF15, and maternal sensitivity to it, both contribute substantially to the risk of HG. We confirmed that higher GDF15 levels in maternal blood are associated with vomiting in pregnancy and HG. Using mass spectrometry to detect a naturally-labelled GDF15 variant we demonstrate that the vast majority of GDF15 in the maternal plasma is derived from the feto-placental unit. By studying carriers of rare and common genetic variants we found that low levels of GDF15 in the non-pregnant state increase the risk of developing HG. Conversely, women with beta-thalassemia, a condition where GDF15 levels are chronically high [5], report very low levels of NVP. In mice, the acute food intake response to a bolus of GDF15 is influenced bi-directionally by prior levels of circulating GDF15 in a manner suggesting that this system is susceptible to desensitization. Our findings support a putative causal role for fetally-derived GDF15 in the nausea and vomiting of human pregnancy, with maternal sensitivity, at least partly determined by pre-pregnancy exposure to the hormone, being a major influence on its severity. They also suggest mechanism-based approaches to the treatment and prevention of HG.</p

The hidden costs of cheap group tours - a case study of business practices in Australia

This paper deals with an issue that has been identified in many markets where there are large numbers of package tourists. In Australia, there have been a number of studies undertaken into the use of a range of dubious business practices employed by Inbound Tour Operators (ITOs), particularly in the Korean market. The cause for this problem is identified as the minimization of the retail price of package tour by transferring part of the cost of the tour to ITOs in the destination country. Under this system, ITOs are paid a daily tour rate below their real costs and are forced to recover losses by employing a range of dubious business practices including forced shopping and kickbacks from shops. The paper models the normal operation of the package tour cycle where no business practices are used and compares this to the Korean package inbound market in Australia where the use of business practices of this nature is widespread