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    Puzzles of the Liminal Dead: St George's University Hospital NHS Foundation Trust v Casey
    (Oxford University Press, 2024-02-08) Donnelly, Mary; Lyons, Barry
    Introduction: St George’s University Hospitals NHS Foundation Trust v Casey [1] is the latest in a growing line of cases before the UK courts concerning objections to the determination of brain stem death (BD). [2] The case is distinguishable from most of the earlier jurisprudence because it concerned an adult [3] and, in this respect, it provides helpful clarity regarding the procedural framework to be applied in such situations. However, as we will see below, in other respects the case serves to increase confusion. One particular problem that arises from the judgment in Casey is how we conceptualise the legal status of an individual who has been found to be brain dead by clinicians, but this finding is disputed by families, either in respect of procedure or substance, and the courts have been asked to rule on the matter. The case also raises new questions about the operationalization of testing for BD, which questions assume particular significance given the ongoing work to revise the Academy of Medical Royal Colleges’ Code of Practice for the Diagnosis and Confirmation of Death (2008) (hereafter ‘the Code’). This commentary will explore both of these aspects of the case. First, however, we outline the facts and identify those areas in which the legal position has been clarified.
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    Envisioning emerging frontiers on human gut microbiota and its applications
    (Wiley, 2020-09) Ventura, Marco; Milani, Christian; Turroni, Francesca; van Sinderen, Douwe; European Commission; Fondazione Cariparma; Science Foundation Ireland; GenProbio
    The human gut microbiota is involved in multiple health-influencing host interactions during the host's entire life span. Microbes colonize the infant gut instantaneously after birth and subsequently the founding and interactive progress of this early gut microbiota is considered to be driven and modulated by different host- and microbe-associated forces. A rising number of studies propose that the composition of the human gut microbiota in the early stages of life impact on the human health conditions at later stages of life. This notion has powered research aimed at detailed investigations of the infant gut microbiota composition. Nevertheless, the molecular mechanisms supporting the gut microbiome functionality and the interaction of the early gut microbes with the human host remain largely unknown.
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    Bifidobacterium breve UCC2003 induces a distinct global transcriptomic program in neonatal murine intestinal epithelial cells
    (Elsevier, 2020-07) Kiu, Raymond; Treveil, Agatha; Harnisch, Lukas C.; Caim, Shabhonam; Leclaire, Charlotte; van Sinderen, Douwe; Korcsmaros, Tamas; Hall, Lindsay J.; Norwich Bioscience Institutes (NBI) Computing infrastructure for Science (CiS) group; Wellcome Trust; Gut Microbes and Health; Genomics for Food security; Norwich Research Park Biosciences; Science Foundation Ireland
    The underlying health-driving mechanisms of Bifidobacterium during early life are not well understood, particularly how this microbiota member may modulate the intestinal barrier via programming of intestinal epithelial cells (IECs). We investigated the impact of Bifidobacterium breve UCC2003 on the transcriptome of neonatal murine IECs. Small IECs from two-week-old neonatal mice administered B. breve UCC2003 or PBS (control) were subjected to global RNA sequencing, and differentially expressed genes, pathways, and affected cell types were determined. We observed extensive regulation of the IEC transcriptome with ∼4,000 genes significantly up-regulated, including key genes linked with epithelial barrier function. Enrichment of cell differentiation pathways was observed, along with an overrepresentation of stem cell marker genes, indicating an increase in the regenerative potential of the epithelial layer. In conclusion, B. breve UCC2003 plays a central role in driving intestinal epithelium homeostatic development during early life and suggests future avenues for next-stage clinical studies.
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    Human milk oligosaccharides: shaping the infant gut microbiota and supporting health
    (Elsevier, 2020-09) Walsh, Clodagh; Lane, Jonathan A.; van Sinderen, Douwe; Hickey, Rita M.; H and H Group; Science Foundation Ireland
    Human milk oligosaccharides (HMO) are complex sugars which are found in breast milk at significant concentrations and with unique structural diversity. These sugars are the fourth most abundant component of human milk after water, lipids, and lactose and yet provide no direct nutritional value to the infant. Recent research has highlighted that HMOs have various functional roles to play in infant development. These sugars act as prebiotics by promoting growth of beneficial intestinal bacteria thereby generating short-chain fatty acids which are critical for gut health. HMOs also directly modulate host-epithelial immune responses and can selectively reduce binding of pathogenic bacteria and viruses to the gut epithelium preventing the emergence of a disease. This review covers current knowledge related to the functional biology of HMOs and their associated impact on infant gut health.
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    From lab bench to formulated ingredient: characterization, production, and commercialization of human milk oligosaccharides
    (Elsevier, 2020-09) Walsh, Clodagh; Lane, Jonathan A.; van Sinderen, Douwe; Hickey, Rita M.; H & H Group; Science Foundation Ireland
    Human milk oligosaccharides (HMOs) are known to positively influence infant health. Extensive variation exists in the levels, diversity, and complexity of oligosaccharides in the milk of a lactating mother. Until recently, limited availability of HMOs hampered their use in clinical applications. Most HMOs are unique to human milk, and have proven difficult and expensive to isolate and synthesize. Added to that, analysis of these complex glycans in milk samples requires state-of-the-art analytical instruments and associated technologies. The current review provides a critical overview of methods used in HMO analysis, and highlights the importance of understanding the factors which influence their composition and structural diversity. We also discuss recently employed strategies to overcome the availability of HMOs at industrial scale including microbial metabolic engineering and chemoenzymatic techniques. Finally, we examine how these recent advancements have opened up new avenues for future research and nutraceutical applications.