Women's Preferences for Treatment of Perinatal Depression and Anxiety : A Discrete Choice Experiment

Perinatal depression and anxiety (PNDA) are an international healthcare priority, associated with significant short- and long-term problems for women, their children and families. Effective treatment is available but uptake is suboptimal: some women go untreated whilst others choose treatments without strong evidence of efficacy. Better understanding of women's preferences for treatment is needed to facilitate uptake of effective treatment. To address this issue, a discrete choice experiment (DCE) was administered to 217 pregnant or postnatal women in Australia, who were recruited through an online research company and had similar sociodemographic characteristics to Australian data for perinatal women. The DCE investigated preferences regarding cost, treatment type, availability of childcare, modality and efficacy. Data were analysed using logit-based models accounting for preference and scale heterogeneity. Predicted probability analysis was used to explore relative attribute importance and policy change scenarios, including how these differed by women's sociodemographic characteristics. Cost and treatment type had the greatest impact on choice, such that a policy of subsidising effective treatments was predicted to double their uptake compared with the base case. There were differences in predicted uptake associated with certain sociodemographic characteristics: for example, women with higher educational attainment were more likely to choose effective treatment. The findings suggest policy directions for decision makers whose goal is to reduce the burden of PNDA on women, their children and families

Normal Human Pluripotent Stem Cell Lines Exhibit Pervasive Mosaic Aneuploidy

Human pluripotent stem cell (hPSC) lines have been considered to be homogeneously euploid. Here we report that normal hPSC – including induced pluripotent - lines are karyotypic mosaics of euploid cells intermixed with many cells showing non-clonal aneuploidies as identified by chromosome counting, spectral karyotyping (SKY) and fluorescent in situ hybridization (FISH) of interphase/non-mitotic cells. This mosaic aneuploidy resembles that observed in progenitor cells of the developing brain and preimplantation embryos, suggesting that it is a normal, rather than pathological, feature of stem cell lines. The karyotypic heterogeneity generated by mosaic aneuploidy may contribute to the reported functional and phenotypic heterogeneity of hPSCs lines, as well as their therapeutic efficacy and safety following transplantation

Extracellular loop 3 of the noradrenaline transporter contributes to substrate and inhibitor selectivity

The human noradrenaline transporter (NET) and 5-hydroxytryptamine (5-HT) transporter (SERT) are inhibited by antidepressants and psychoactive drugs such as cocaine. Both substrates and inhibitors bind in the transmembrane core of the protein, but molecular divergence at the binding site is not sufficient to account for the NET-selective and SERT-selective inhibition of the antidepressants, desipramine and citalopram, respectively. We considered that the poorly conserved third extracellular loop may contribute to these differences. We substituted single amino acid residues of the third extracellular loop in NET for equivalents from SERT, transiently transfected COS-7 cells with WT NET, 13 mutant NETs and WT SERT, and measured [ 3H]noradrenaline uptake, [3H]nisoxetine binding and [ 3H]5-HT uptake. Mutants F299W, Y300Q, R301K and K303L, at the C-terminal end of EL3, all showed significantly decreased [3H] nisoxetine binding, indicative of a reduced cell surface expression. Most mutants differed little, if at all, from WT NET regarding [3H] noradrenaline uptake; however, the I297P mutant showed no significant uptake activity despite intact cell surface expression, and the A293F mutant showed a significantly slower transporter turnover than WT NET in addition to [ 3H]5-HT uptake that was significantly greater than that of WT NET. The A293F mutation also decreased desipramine potency and increased the inhibition of [3H]noradrenaline uptake by citalopram compared to WT NET. These results suggest that the third extracellular loop allosterically regulates the ability of the transmembrane domains to transport substrates and bind inhibitors and thus contributes to the selectivity of substrates and antidepressants for NET and SERT

When does hardship matter for health? Neighborhood and individual disadvantages and functional somatic symptoms from adolescence to mid-life in the Northern Swedish Cohort.

A large body of research has shown that health is influenced by disadvantaged living conditions, including both personal and neighborhood conditions. Little is however known to what degree the health impact of different forms of disadvantage differ along the life course. The present study aims to examine when, during the life course, neighborhood and individual disadvantages relate to functional somatic symptoms. Participants (n = 992) came from The Northern Swedish Cohort and followed from age 16, 21, 30 until 42 years. Functional somatic symptoms, socioeconomic disadvantage, and social and material adversity were measured through questionnaires and linked to register data on neighborhood disadvantage. Data was analyzed with longitudinal and cross-sectional multilevel models. Results showed that neighborhood disadvantage, social and material adversity and gender all contributed independently to overall levels of symptoms across the life course. Cross-sectional analyses also suggested that the impact of disadvantage differed between life course periods; neighborhood disadvantage was most important in young adulthood, and the relative importance of material versus social adversity increased as participants grew older. In summary, the study suggests that disadvantages from different contextual sources may affect functional somatic health across the life course, but also through life course specific patterns