Factors that influence E. coli folate synthesis and their impact on C. elegans ageing

Microbes can exert both positive and negative effects on animal health and longevity. The nematode worm, Caenorhabditis elegans, and its bacterial diet, Escherichia. coli, provide a simplified model to study animal-microbe interactions. Inhibiting E. coli folate synthesis has been found to increase C. elegans lifespan without any negative effects on either organism. Specifically disrupting worm folate uptake or metabolism was not found to influence lifespan and it was therefore hypothesized that a folate-dependent bacterial activity modulates ageing. This thesis aims to understand the factors that influence bacterial folate synthesis with the ultimate aim of understanding how bacterial folate affects C. elegans ageing

Exploring the mechanisms that underpin an effective community first aid response: a rapid realist review

Background Community First Aid (CFA) interventions aim to improve the capacity of a community to effectively respond to urgent and emergency health needs, by providing training, education or response services. With urgent and emergency services under sustained pressure, there is growing interest in understanding how targeted and tailored CFA interventions might help improve health outcomes and mitigate demand on the health system. Understanding the underlying mechanisms of effective CFA interventions can help optimise their design, delivery and evaluation.  Methods We conducted a rapid realist review to explore how CFA interventions work, for whom, and in what settings. MEDLINE was searched for relevant peer-reviewed articles and search results supplemented with relevant grey literature and additional articles identified by the research team. Middle-range theory was drawn upon to help synthesise findings and formulate Context-Mechanism-Outcome configurations. Findings  The majority of the 46 included articles focused on CFA training interventions. By drawing on the Theory of Planned Behaviour, we formulated mechanisms which either tackle the barriers communities face, or draw on inherent enabling characteristics of communities, to improve perceived behavioural control, attitudes and subjective norms related to intention to perform FA. Conclusion  By understanding community needs and characteristics and how they influence effective CFA responses, FA training and education interventions can be targeted and tailored, ultimately improving the intention of communities to perform effective FA. Communities should be involved in the co-design of CFA interventions

Atmospheric oxygen regulation at low Proterozoic levels by incomplete oxidative weathering of sedimentary organic carbon

It is unclear why atmospheric oxygen remained trapped at low levels for more than 1.5 billion years following the Paleoproterozoic Great Oxidation Event. Here, we use models for erosion, weathering and biogeochemical cycling to show that this can be explained by the tectonic recycling of previously accumulated sedimentary organic carbon, combined with the oxygen sensitivity of oxidative weathering. Our results indicate a strong negative feedback regime when atmospheric oxygen concentration is of order pO2∼0.1 PAL (present atmospheric level), but that stability is lost at pO2<0.01 PAL. Within these limits, the carbonate carbon isotope (δ13C) record becomes insensitive to changes in organic carbon burial rate, due to counterbalancing changes in the weathering of isotopically light organic carbon. This can explain the lack of secular trend in the Precambrian δ13C record, and reopens the possibility that increased biological productivity and resultant organic carbon burial drove the Great Oxidation Event

Alterations in Bacterial Metabolism Contribute to the Lifespan Extension Exerted by Guarana in Caenorhabditis elegans

Guarana (Paullinia cupana) is a widely consumed nutraceutical with various health benefits supported by scientific evidence. However, its indirect health impacts through the gut microbiota have not been studied. Caenorhabditis elegans is a useful model to study both the direct and indirect effects of nutraceuticals, as the intimate association of the worm with the metabolites produced by Escherichia coli is a prototypic simplified model of our gut microbiota. We prepared an ethanoic extract of guarana seeds and assessed its antioxidant capacity in vitro, with a 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay, and in vivo, utilizing C. elegans. Additionally, we studied the impact of this extract on C. elegans lifespan, utilizing both viable and non-viable E. coli, and assessed the impact of guarana on E. coli folate production. The extract showed high antioxidant capacity, and it extended worm lifespan. However, the antioxidant and life-extending effects did not correlate in terms of the extract concentration. The extract-induced life extension was also less significant when utilizing dead E. coli, which may indicate that the effects of guarana on the worms work partly through modifications on E. coli metabolism. Following this observation, guarana was found to decrease E. coli folate production, revealing one possible route for its beneficial effects

Alterations in Bacterial Metabolism Contribute to the Lifespan Extension Exerted by Guarana in Caenorhabditis elegans

Guarana (Paullinia cupana) is a widely consumed nutraceutical with various health benefits supported by scientific evidence. However, its indirect health impacts through the gut microbiota have not been studied. Caenorhabditis elegans is a useful model to study both the direct and indirect effects of nutraceuticals, as the intimate association of the worm with the metabolites produced by Escherichia coli is a prototypic simplified model of our gut microbiota. We prepared an ethanoic extract of guarana seeds and assessed its antioxidant capacity in vitro, with a 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay, and in vivo, utilizing C. elegans. Additionally, we studied the impact of this extract on C. elegans lifespan, utilizing both viable and non-viable E. coli, and assessed the impact of guarana on E. coli folate production. The extract showed high antioxidant capacity, and it extended worm lifespan. However, the antioxidant and life-extending effects did not correlate in terms of the extract concentration. The extract-induced life extension was also less significant when utilizing dead E. coli, which may indicate that the effects of guarana on the worms work partly through modifications on E. coli metabolism. Following this observation, guarana was found to decrease E. coli folate production, revealing one possible route for its beneficial effects

Peas, please! Food familiarization though picture books helps parents introduce vegetables into preschoolers' diets

Repeated taste exposure is an established means of increasing children’s liking and intake of fruit and vegetables. However, parents find it difficult to offer children disliked foods repeatedly, often giving up after a few attempts. Studies show that familiarizing children to fruit and vegetables through picture books can increase their interest in tasting targeted foods. This study explored whether looking at picture books before providing foods to taste improved the outcomes of a home-delivered taste exposure regime. Parents of 127 toddlers (aged 21-24 months) identified two ‘target’ foods they wanted their child to eat (1 fruit, 1 vegetable). Families were randomly assigned to one of three groups. Parents and children in two experimental groups looked at books about either the target fruit or vegetable every day for two weeks; the control group did not receive a book. Parents in all three groups were then asked to offer their child both target foods every day during a 2-week taste-exposure phase. Parental ratings of children’s liking and consumption of the foods were collected at baseline, immediately following taste-exposure (post-intervention), and 3 months later (follow-up). In all groups, liking of both foods increased following taste exposure and remained above baseline at follow-up (all ps<.001). In addition, compared to the control group who experienced only taste exposure, looking at vegetable books enhanced children’s liking of their target vegetable post-intervention (p<.001) and at follow-up (p<.05), and increased consumption of the vegetable at follow-up (p<.01). Exposure to vegetable books was also associated with smaller increases in neophobia and food fussiness over the period of the study compared to controls (ps<.01), suggesting that picture books may have positive, long-term impacts on children’s attitudes towards new foods

Adjuvant radiotherapy following neo-adjuvant chemotherapy and surgery in oesophageal cancer: a retrospective cohort study of survival

Following surgery for oesophageal cancer, positive circumferential resection margin (CRM) (R1), defined as margin <1mm, is an associated predictor of poor survival. The role of selective adjuvant radiotherapy in patients with R1 margin following neo-adjuvant chemotherapy (NACT) is unclear. We investigated survival outcomes following adjuvant radiotherapy in patients undergoing NACT with R1 margin from oesophageal surgery

Early Emergence of Ethnic Differences in Type 2 Diabetes Precursors in the UK: The Child Heart and Health Study in England (CHASE Study)

Peter Whincup and colleagues carry out a cross-sectional study examining ethnic differences in precursors of of type 2 diabetes among children aged 9–10 living in three UK cities

Differential Effect of TLR2 and TLR4 on the Immune Response after Immunization with a Vaccine against Neisseria meningitidis or Bordetella pertussis

Neisseria meningitidis and Bordetella pertussis are Gram-negative bacterial pathogens that can cause serious diseases in humans. N. meningitidis outer membrane vesicle (OMV) vaccines and whole cell pertussis vaccines have been successfully used in humans to control infections with these pathogens. The mechanisms behind their effectiveness are poorly defined. Here we investigated the role of Toll-like receptor (TLR) 2 and TLR4 in the induction of immune responses in mice after immunization with these vaccines. Innate and adaptive immune responses were compared between wild type mice and mice deficient in TLR2, TLR4, or TRIF. TRIF-deficient and TLR4-deficient mice showed impaired immunity after immunization. In contrast, immune responses were not lower in TLR2−/− mice but tended even to be higher after immunization. Together our data demonstrate that TLR4 activation contributes to the immunogenicity of the N. meningitidis OMV vaccine and the whole cell pertussis vaccine, but that TLR2 activation is not required