Imaging of activated complement using ultrasmall superparamagnetic iron oxide particles (USPIO) - conjugated vectors: an in vivo in utero non-invasive method to predict placental insufficiency and abnormal fetal brain development.

In the current study, we have developed a magnetic resonance imaging-based method for non-invasive detection ofcomplement activation in placenta and foetal brain in vivo in utero. Using this method, we found that anti-complementC3-targeted ultrasmall superparamagnetic iron oxide (USPIO) nanoparticles bind within the inflamed placenta and foetal braincortical tissue, causing a shortening of the T2* relaxation time. We used two mouse models of pregnancy complications: a mousemodel of obstetrics antiphospholipid syndrome (APS) and a mouse model of preterm birth (PTB). We found that detection of C3deposition in the placenta in the APS model was associated with placental insufficiency characterised by increased oxidative stress,decreased vascular endothelial growth factor and placental growth factor levels and intrauterine growth restriction. We alsofound that foetal brain C3 deposition was associated with cortical axonal cytoarchitecture disruption and increasedneurodegeneration in the mouse model of APS and in the PTB model. In the APS model, foetuses that showed increased C3in their brains additionally expressed anxiety-related behaviour after birth. Importantly, USPIO did not affect pregnancyoutcomes and liver function in the mother and the offspring, suggesting that this method may be useful for detecting complementactivation in vivo in utero and predicting placental insufficiency and abnormal foetal neurodevelopment that leads toneuropsychiatric disorders

LGBTQ parenting post heterosexual relationship dissolution

The chapter examines parenting among sexual and gender minorities post heterosexual relationship dissolution (PHRD). Reviewing the literature around intersecting identities of LGBTQ parents, we consider how religion, race, and socioeconomic status are associated with routes into and out of heterosexual relationships and variation in the lived experience of sexual and gender identity minorities, in particular how LGBTQ parents PHRD feel about being out. Further consideration is given to examining how family relationships change and develop as parental sexual and/or gender identity changes. We also explore the impact of PHRD identity and parenthood on new partnerships and stepfamily experiences. The chapter addresses the reciprocal relationship between research on LGBTQ parenting and policy and legal influences that impact upon the experience of LGBTQ parenting PHRD when custody and access are disputed. Finally, the chapter includes future research directions and implications for practice in an area that has been revitalized in recent years

Effects of complement regulators bound to Escherichia coli K1 and Group B Streptococcus on the interaction with host cells

Escherichia coli K1 and Group B Streptococcus (GBS) are the most common bacteria that cause meningitis during the neonatal period. Complement, the first line of defence in the host, acts on these bacteria to opsonize with various components of complement for subsequent presentation to phagocytes. To counteract these opsonization effects, E. coli and GBS bind to the complement regulators C4 binding protein and Factor H, respectively. Nonetheless, the deposition of complement components on these two bacteria from neonatal serum and their effect on the host cell interaction is unclear. Here we demonstrated that the deposition of complement proteins from adult serum prevented the invasion of E. coli into human brain microvascular endothelial cells, whereas the invasion of GBS was enhanced. In contrast, treatment with cord serum had no effect on the invasion of both these bacteria. We also examined the effect of the deposited complement proteins on phagocytosis using THP-1 cells and THP-1 cells differentiated into macrophages. Escherichia coli treated with adult serum neither attached nor entered these cells, whereas GBS was phagocytosed and survived efficiently. We further demonstrate that the inhibitory effect of complement proteins is the result of the bound complement inhibitors C4b-binding protein, in the case of E. coli, and Factor H, in the case of GBS. Taken together, these results suggest that E. coli and GBS utilize contrasting mechanisms of complement-mediated interactions with their target cells for successful establishment of disease