Emotional health screening of mothers, preliminary validation of a 3-item instrument: A research brief.

A number of countries now recommend population-wide depression screening for perinatal women, using validated tools. A stepped-approach to screening - involving universal screening with a brief measure, followed by targeted screening using a longer measure for those women identified as at greater risk - is used in some settings. This brief report describes the test performance characteristics of a 3-item mood screening instrument, developed for use within a digital parenting program. Participants (n = 404) in this cross-sectional study were mothers of children aged up to 3 years. The majority (65.5 %) were first-time mothers, and their mean age was 32.8 years. Data were collected using an online survey. The test performance of the brief 3-item mood screening instrument (possible score range = 0-300) was examined using Receiver Operating Characteristic (ROC) analysis, with a score of 13 or more on the Edinburgh Postnatal Depression Scale (EPDS) used as the reference standard. The mood screening instrument demonstrated excellent range when compared to the reference standard. Optimal balance between sensitivity (0.77) and specificity (0.78), was achieved at a cut-point of 160 or less. Analysis was limited by using only the EPDS as the reference standard. This preliminary data supports the use of this 3-item mood screening instrument to screen for postnatal depression symptoms and may be integrated into a mobile Health or online tool. Future research should examine the test performance of the 3-item mood screening instrument against a diagnostic tool.

sFRP2 in the aged microenvironment drives melanoma metastasis and therapy resistance.

Cancer is a disease of ageing. Clinically, aged cancer patients tend to have a poorer prognosis than young. This may be due to accumulated cellular damage, decreases in adaptive immunity, and chronic inflammation. However, the effects of the aged microenvironment on tumour progression have been largely unexplored. Since dermal fibroblasts can have profound impacts on melanoma progression, we examined whether age-related changes in dermal fibroblasts could drive melanoma metastasis and response to targeted therapy. Here we find that aged fibroblasts secrete a Wnt antagonist, sFRP2, which activates a multi-step signalling cascade in melanoma cells that results in a decrease in ß-catenin and microphthalmia-associated transcription factor (MITF), and ultimately the loss of a key redox effector, APE1. Loss of APE1 attenuates the response of melanoma cells to DNA damage induced by reactive oxygen species, rendering the cells more resistant to targeted therapy (vemurafenib). Age-related increases in sFRP2 also augment both angiogenesis and metastasis of melanoma cells. These data provide an integrated view of how fibroblasts in the aged microenvironment contribute to tumour progression, offering new possibilities for the design of therapy for the elderly.

Wnt5A promotes an adaptive, senescent-like stress response, while continuing to drive invasion in melanoma cells.

We have previously shown that Wnt5A drives invasion in melanoma. We have also shown that Wnt5A promotes resistance to therapy designed to target the BRAF(V600E) mutation in melanoma. Here, we show that melanomas characterized by high levels of Wnt5A respond to therapeutic stress by increasing p21 and expressing classical markers of senescence, including positivity for senescence-associated ß-galactosidase (SA-ß-gal), senescence-associated heterochromatic foci (SAHF), H3K9Me chromatin marks, and PML bodies. We find that despite this, these cells retain their ability to migrate and invade. Further, despite the expression of classic markers of senescence such as SA-ß-gal and SAHF, these Wnt5A-high cells are able to colonize the lungs in in vivo tail vein colony-forming assays. This clearly underscores the fact that these markers do not indicate true senescence in these cells, but instead an adaptive stress response that allows the cells to evade therapy and invade. Notably, silencing Wnt5A reduces expression of these markers and decreases invasiveness. The combined data point to Wnt5A as a master regulator of an adaptive stress response in melanoma, which may contribute to therapy resistance.