Typologies of postnatal support and breastfeeding at two months in the UK.

There is extensive evidence to suggest that social support improves breastfeeding outcomes. Building on this evidence-base, public health services and interventions aiming to improve breastfeeding rates have primarily targeted informational and emotional support to mothers, reflecting an individual behaviour-change approach. However, mothers exist within a wider social network, and the characteristics of their broader support networks may be an important predictor of breastfeeding outcomes. Here we explore the typologies of postnatal support for mothers in the UK; a population with one of the lowest breastfeeding rates in Europe. Using retrospective data from an online survey (data collection period December 2017 - February 2018), we carry out a latent class regression (n = 432) to identify "clusters" of postnatal support in our data. Mothers in our sample were most likely to report receiving practical and emotional support from partners and maternal grandmothers, and breastfeeding information from health professionals. We identify three distinct typologies of postnatal support: 1) Extensive support, where mothers received support from a wide range of supporters including partners, maternal grandmothers, friends and health professionals, but mothers were the only ones to feed the infant; 2) Family support, where mothers received support from partners and maternal grandmothers, including with infant feeding, but less likely to receive support from health professionals; and 3) Low support, where mothers primarily received support from partners. 94% of women with extensive support were predicted to be breastfeeding at two months, followed by 48% of mothers in the low support group, and 13% in the family support group. Our findings highlight the complexities of family support and its potential impact on breastfeeding, as well as the significance of professional support. Overall, our results hint at the potential value for health professionals to engage with wider family in order to achieve extensive support for mothers

Subjective environmental experiences and women’s breastfeeding journeys: a survival analysis using an online survey of UK mothers

Local physical and social environmental factors are important drivers of human health and behaviour. Environmental perception has been linked with both reproduction and parenting, but links between subjective environmental experiences and breastfeeding remain unclear. Using retrospective data from an online survey of UK mothers of children aged 0–24 months, Cox-Aalen survival models test whether negative subjective environmental experiences negatively correlated with any and exclusive breastfeeding (max n = 473). Matching predictions, hazards of stopping any breastfeeding were increased, albeit non-significantly, across the five environmental measures (HR: 1.05–1.26) Hazards for stopping exclusive breastfeeding were however (non-significantly) reduced (HR: 0.65–0.87). Score processes found no significant time-varying effects. However, estimated cumulative coefficient graphs showed that the first few weeks postpartum were most susceptible to environmental influences and that contrary to our predictions, mothers with worse subjective environmental experiences were less likely to stop breastfeeding at this time. In addition, the hazard of stopping exclusive breastfeeding declined over time for mothers who thought that littering was a problem. The predicted increased hazards of stopping breastfeeding were only evident in the later stages of any breastfeeding and only for mothers who reported littering as a problem or that people tended not to know each other. Perceived harsher physical and social environmental conditions are assumed to deter women from breastfeeding, but this may not always be the case. Women’s hazards of stopping breastfeeding change over time and there may be particular timepoints in their breastfeeding journeys where subjective environmental experiences play a rol

Ifit1 regulates norovirus infection and enhances the interferon response in murine macrophage-like cells [version 1; peer review: 1 approved, 2 approved with reservations]

Background: Norovirus, also known as the winter vomiting bug, is the predominant cause of non-bacterial gastroenteritis worldwide. Disease control is predicated on a robust innate immune response during the early stages of infection. Double-stranded RNA intermediates generated during viral genome replication are recognised by host innate immune sensors in the cytoplasm, activating the strongly antiviral interferon gene programme. Ifit proteins (interferon induced proteins with tetratricopeptide repeats), which are highly expressed during the interferon response, have been shown to directly inhibit viral protein synthesis as well as regulate innate immune signalling pathways. Ifit1 is well-characterised to inhibit viral translation by sequestration of eukaryotic initiation factors or by directly binding to the 5' terminus of foreign RNA, particularly those with non-self cap structures. However, noroviruses have a viral protein, VPg, covalently linked to the 5' end of the genomic RNA, which acts as a cap substitute to recruit the translation initiation machinery. Methods: : Ifit1 knockout RAW264.7 murine macrophage-like cells were generated using CRISPR-Cas9 gene editing. These cells were analysed for their ability to support murine norovirus infection, determined by virus yield, and respond to different immune stimuli, assayed by quantitative PCR. The effect of Ifit proteins on norovirus translation was also tested in vitro . Results: : Here, we show that VPg-dependent translation is completely refractory to Ifit1-mediated translation inhibition in vitro and Ifit1 cannot bind the 5' end of VPg-linked RNA. Nevertheless, knockout of Ifit1 promoted viral replication in murine norovirus infected cells. We then demonstrate that Ifit1 promoted interferon-beta expression following transfection of synthetic double-stranded RNA but had little effect on toll-like receptor 3 and 4 signalling. Conclusions: : Ifit1 is an antiviral factor during norovirus infection but cannot directly inhibit viral translation. Instead, Ifit1 stimulates the antiviral state following cytoplasmic RNA sensing, contributing to restriction of norovirus replication

Cohort profile: Children in Need Census (CIN) records of children referred for social care support in England

Purpose The Children in Need Census (CIN) is a casebased administrative dataset on children referred to social care services in England. CIN includes information on the ‘needs’ of children, and whether they received social care support. Local and national government bodies in England currently use CIN for evaluation purposes. Data are accessible to researchers under certain conditions, allowing researchers to investigate the health implications of adverse childhood experiences. However, CIN suffers from lack of metadata, meaning it can be challenging for researchers to process and interpret data, particularly if researchers are unfamiliar with the English children’s social care system. To address this issue, we provide the background to CIN and describe the available data from 2008 to 2016. Participants CIN is derived from case records held by English local authorities on all children referred to children’s social care for a ‘needs assessment’, regardless of whether they are eventually assessed as ‘in need of social care support’. Local authorities submit these case records to the UK Department for Education for collation. CIN holds information on an estimated 2.76million children from October 2008 to March 2016. Since 2013/2014, just under 900 000 children have been recorded in the CIN annually, equivalent to around 8% of children in England (annual prevalence). Approximately, 650 000 children enter or renter the dataset each year, equivalent to 5% of children in England (annual incidence). Data summary Of the estimated 2.76million children in the data, 50% are male and 47% female. 45% are referred to children’s social care services due to abuse or neglect. 10.7% of children in CIN went onto a child protection plan, meaning they were judged to be (at risk of) suffering significant harm. Future plans CIN data collection is annual and ongoing. Data from the most recent census period typically become available for researchers in the following Spring

Testing the buffering hypothesis: Breastfeeding problems, cessation, and social support in the UK.

OBJECTIVES: Physical breastfeeding problems can lead women to terminate breastfeeding earlier than planned. In high-income countries such as the UK, breastfeeding problems have been attributed to the cultural and individual "inexperience" of breastfeeding, ultimately leading to lower breastfeeding rates. Yet, cross-cultural evidence suggests breastfeeding problems still occur in contexts where breastfeeding is common, prolonged, and seen publicly. This suggests breastfeeding problems are not unusual and do not necessarily lead to breastfeeding cessation. As humans evolved to raise children cooperatively, what matters for breastfeeding continuation may be the availability of social support during the postnatal period. Here, we test the hypothesis that social support buffers mothers from the negative impact breastfeeding problems have on duration. METHODS: We run Cox models on a sample of 565 UK mothers who completed a retrospective online survey about infant feeding and social support in 2017-2018. RESULTS: Breastfeeding problems were important predictors of cessation; however, the direction of the effect was dependent on the problem type and type of support from a range of supporters. Helpful support for discomfort issues (blocked ducts, too much milk) was significantly associated with reduced hazards of cessation, as predicted. However, helpful support for reported milk insufficiency was assoicated with an increased hazard of cessation. CONCLUSIONS: Experiencing breastfeeding problems is the norm, but its impact may be mitigated via social support. Working from an interdisciplinary approach, our results highlight that a wide range of supporters who provide different types of support have potential to influence maternal breastfeeding experience

Who cares for women with children? Crossing the bridge between disciplines.

It has long been acknowledged that women with children require social support to promote their health and wellbeing, as well as that of their children. However, the dominant conceptualizations of support have been heavily influenced by Western family norms. The consequence, at best, has been to stifle our understanding of the nature and consequences of support for mothers and children. At worst, it has led to systematic discrimination negatively impacting maternal-child health. To fully engage with the complexities of social support, we must take multidisciplinary or interdisciplinary approaches spanning diverse cultural and geographical perspectives. However, multidisciplinary knowledge-processing can be challenging, and it is often unclear how different studies from different disciplines relate. To address this, we outline two epistemological frameworks-the scientific approach and Tinbergen's four questions-that can be useful tools in connecting research across disciplines. In this theme issue on 'Multidisciplinary perspectives on social support and maternal-child health', we attempt to foster multidisciplinary thinking by presenting work from a diverse range of disciplines, populations and cultures. Our hope is that these tools, along with papers in this issue, help to build a holistic understanding of social support and its consequences for mothers and their children. Overall, a multidisciplinary perspective points to how the responsibility of childrearing should not fall solely onto mothers. Indeed, this multidisciplinary issue demonstrates that successful childrearing is consistently an activity shared beyond the mother and the nuclear family: an insight that is crucial to harnessing the potential of social support to improve maternal-child health. This article is part of the theme issue 'Multidisciplinary perspectives on social support and maternal-child health'

VPS18 recruits VPS41 to the human HOPS complex via a RING-RING interaction

Eukaryotic cells use conserved multisubunit membrane tethering complexes, including CORVET (class C core vacuole/endosome tethering) and HOPS (homotypic fusion and vacuole protein sorting), to control the fusion of endomembranes. These complexes have been extensively studied in yeast, but to date there have been far fewer studies of metazoan CORVET and HOPS. Both of these complexes comprise six subunits: a common four-subunit core and two unique subunits. Once assembled, these complexes function to recognise specific endosomal membrane markers and facilitate SNARE-mediated membrane fusion. CORVET promotes the homotypic fusion of early endosomes, while HOPS promotes the fusion of lysosomes to late endosomes and autophagosomes. Many of the subunits of both CORVET and HOPS contain putative C-terminal zinc-finger domains. Here, the contribution of these domains to the assembly of the human CORVET and HOPS complexes has been examined. Using biochemical techniques, we demonstrate that the zinc-containing RING (really interesting new gene) domains of human VPS18 and VPS41 interact directly to form a stable heterodimer. In cells, these RING domains are able to integrate into endogenous HOPS, showing that the VPS18 RING domain is required to recruit VPS41 to the core complex subunits. Importantly, this mechanism is not conserved throughout eukaryotes, as yeast Vps41 does not contain a C-terminal zinc-finger motif. The subunit analogous to VPS41 in human CORVET is VPS8, in which the RING domain has an additional C-terminal segment that is predicted to be disordered. Both the RING and disordered C-terminal domains are required for integration of VPS8 into endogenous CORVET complexes, suggesting that HOPS and CORVET recruit VPS41 and VPS8 via distinct molecular interactions.This work was supported by a Sir Henry Dale Fellowship, jointly funded by the Royal Society and the Wellcome Trust, to S.C.G. [098406/Z/12/Z], an Isaac Newton Trust/Wellcome Trust ISSF/University of Cambridge Joint Research Grant to S.C.G., and a Wellcome Trust Senior Research Fellowship [WT097997MA] to Ian Goodfellow (University of Cambridge)

Children are important too: juvenile playgroups and maternal childcare in a foraging population, the Agta

Non-maternal carers (allomothers) are hypothesized to lighten the mother's workload, allowing for the specialized human life history including relatively short interbirth intervals and multiple dependent offspring. Here, using in-depth observational data on childcare provided to 78 Agta children (a foraging population in the northern Philippines; aged 0–6 years), we explore whether allomaternal childcare substitutes and decreases maternal childcare. We found that allomother caregiving was associated with reduced maternal childcare, but the substitutive effect varied depending on the source and type of care. Children-only playgroups consistently predicted a decrease in maternal childcare. While grandmothers were rarely available, their presence was negatively associated with maternal presence and childcare, and grandmothers performed similar childcare activities to mothers. These results underscore the importance of allomothering in reducing maternal childcare in the Agta. Our findings suggest that flexibility in childcare sources, including children-only playgroups, may have been the key to human life-history evolution. Overall, our results reinforce the necessity of a broad conceptualization of social support in human childcare. This article is part of the theme issue ‘Multidisciplinary perspectives on social support and maternal–child health’

Adenovirus type 5 E4 Orf3 protein targets promyelocytic leukaemia (PML) protein nuclear domains for disruption via a sequence in PML isoform II that is predicted as a protein interaction site by bioinformatic analysis

Human adenovirus type 5 infection causes the disruption of structures in the cell nucleus termed promyelocytic leukaemia (PML) protein nuclear domains or ND10, which contain the PML protein as a critical component. This disruption is achieved through the action of the viral E4 Orf3 protein, which forms track-like nuclear structures that associate with the PML protein. This association is mediated by a direct interaction of Orf3 with a specific PML isoform, PMLII. We show here that the Orf3 interaction properties of PMLII are conferred by a 40 aa residue segment of the unique C-terminal domain of the protein. This segment was sufficient to confer interaction on a heterologous protein. The analysis was informed by prior application of a bioinformatic tool for the prediction of potential protein interaction sites within unstructured protein sequences (predictors of naturally disordered region analysis; PONDR). This tool predicted three potential molecular recognition elements (MoRE) within the C-terminal domain of PMLII, one of which was found to form the core of the Orf3 interaction site, thus demonstrating the utility of this approach. The sequence of the mapped Orf3-binding site on PML protein was found to be relatively poorly conserved across other species; however, the overall organization of MoREs within unstructured sequence was retained, suggesting the potential for conservation of functional interactions