The ABA intervention for improving breastfeeding initiation and continuation: Feasibility study results

The UK has low breastfeeding rates, with socioeconomic disparities. The Assets‐based feeding help Before and After birth (ABA) intervention was designed to be inclusive and improve infant feeding behaviours. ABA is underpinned by the behaviour change wheel and offers an assets‐based approach focusing on positive capabilities of individuals and communities, including use of a Genogram. This study aimed to investigate feasibility of intervention delivery within a randomised controlled trial (RCT). Nulliparous women ≥16 years, (n = 103) from two English sites were recruited and randomised to either intervention or usual care. The intervention – delivered through face‐to‐face, telephone and text message by trained Infant Feeding Helpers (IFHs) – ran from 30‐weeks' gestation until 5‐months postnatal. Outcomes included recruitment rates and follow‐up at 3‐days, 8‐weeks and 6‐months postnatal, with collection of future full trial outcomes via questionnaires. A mixed‐methods process evaluation included qualitative interviews with 30 women, 13 IFHs and 17 maternity providers; IFH contact logs; and fidelity checking of antenatal contact recordings. This study successfully recruited women, including teenagers, from socioeconomically disadvantaged areas; postnatal follow‐up rates were 68.0%, 85.4% and 80.6% at 3‐days, 8‐weeks and 6‐months respectively. Breastfeeding at 8‐weeks was obtained for 95.1% using routine data for non‐responders. It was possible to recruit and train peer supporters to deliver the intervention with adequate fidelity. The ABA intervention was acceptable to women, IFHs and maternity services. There was minimal contamination and no evidence of intervention‐related harm. In conclusion, the intervention is feasible to deliver within an RCT, and a definitive trial required.     

The use of Trichomonas vaginalis purine nucleoside phosphorylase to activate fludarabine in the treatment of solid tumors

Treatment with fludarabine phosphate (9-β-D-arabinofuranosyl-2-F-adenine 5′-phosphate, F-araAMP) leads to regressions and cures of human tumor xenografts that express Escherichia coli purine nucleoside phosphorylase (EcPNP). This occurs despite the fact that fludarabine (F-araA) is a relatively poor substrate for EcPNP, and is cleaved to liberate 2-fluoroadenine at a rate only 0.3% that of the natural E. coli PNP substrate, adenosine. In this study, we investigated a panel of naturally occurring PNPs to identify more efficient enzymes that may be suitable for metabolizing F-araA as part of experimental cancer therapy. We show that Trichomonas vaginalis PNP (TvPNP) cleaves F-araA with a catalytic efficiency 25-fold greater than the prototypic E. coli enzyme. Cellular extracts from human glioma cells (D54) transduced with lentivirus stably expressing TvPNP (D54/TvPNP) were found to cleave F-araA at a rate similar to extracts from D54 cells expressing EcPNP, although much less enzyme was expressed per cell in the TvPNP transduced condition. As a test of safety and efficacy using TvPNP, human head and neck squamous cell carcinoma (FaDu) xenografts expressing TvPNP were studied in nude mice and shown to exhibit robust tumor regressions, albeit with partial weight loss that resolved post-therapy. F-araAMP was also a very effective treatment for mice bearing D54/TvPNP xenografts in which approximately 10% of tumor cells expressed the enzyme, indicating pronounced ability to kill non-transduced tumor cells (high bystander activity). Moreover, F-araAMP demonstrated activity against D54 tumors injected with an E1, E3 deleted adenoviral vector encoding TvPNP. In that setting, despite higher F-araA cleavage activity using TvPNP, tumor responses were similar to those obtained with EcPNP, indicating factors other than F-Ade production may limit regressions of the D54 murine xenograft model. Our results establish that TvPNP is a favorable enzyme for activating F-araA, and support further studies in combination with F-araAMP for difficult-to-treat human cancers.     

The relationship between childhood maltreatment and psychopathology in adults undergoing bariatric surgery

Background

A history of childhood maltreatment and psychopathology are common in adults with obesity.