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- Alemany, S., et al.
(author)
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Genome-wide multi-trait analysis of irritable bowel syndrome and related mental conditions identifies 38 new independent variants
- 2023
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In: Journal of Translational Medicine. ; 21:1
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Journal article (peer-reviewed)abstract
- BackgroundIrritable bowel syndrome (IBS) is a chronic disorder of gut-brain interaction frequently accompanied by mental conditions, including depression and anxiety. Despite showing substantial heritability and being partly determined by a genetic component, the genetic underpinnings explaining the high rates of comorbidity remain largely unclear and there are no conclusive data on the temporal relationship between them. Exploring the overlapping genetic architecture between IBS and mental conditions may help to identify novel genetic loci and biological mechanisms underlying IBS and causal relationships between them.MethodsWe quantified the genetic overlap between IBS, neuroticism, depression and anxiety, conducted a multi-trait genome-wide association study (GWAS) considering these traits and investigated causal relationships between them by using the largest GWAS to date.ResultsIBS showed to be a highly polygenic disorder with extensive genetic sharing with mental conditions. Multi-trait analysis of IBS and neuroticism, depression and anxiety identified 42 genome-wide significant variants for IBS, of which 38 are novel. Fine-mapping risk loci highlighted 289 genes enriched in genes upregulated during early embryonic brain development and gene-sets related with psychiatric, digestive and autoimmune disorders. IBS-associated genes were enriched for target genes of anti-inflammatory and antirheumatic drugs, anesthetics and opioid dependence pharmacological treatment. Mendelian-randomization analysis accounting for correlated pleiotropy identified bidirectional causal effects between IBS and neuroticism and depression and causal effects of the genetic liability of IBS on anxiety.ConclusionsThese findings provide evidence of the polygenic architecture of IBS, identify novel genome-wide significant variants for IBS and extend previous knowledge on the genetic overlap and relationship between gastrointestinal and mental disorders.
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- van den Nieuwboer, M., et al.
(author)
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Safety of probiotics and synbiotics in children under 18 years of age
- 2015
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In: Beneficial Microbes. - : Wageningen Academic Publishers. - 1876-2883 .- 1876-2891. ; 6:5, s. 615-630
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Journal article (peer-reviewed)abstract
- This study aimed to systematically evaluate safety of probiotics and synbiotics in children ageing 0-18 years. This study is the third and final part in a safety trilogy and an update is provided using the most recent available clinical data (2008-2013) by means of the Common Terminology Clinical Adverse Events (CTCAE version 4.0) classification. Safety aspects are represented and related to number of participants per probiotic strain/culture, study duration, dosage, clinical condition and selected afflictions. Analysis of 74 clinical studies indicated that probiotic and/or synbiotic administration in children is safe with regard to the specific evaluated strains, dosages and duration. The population of children include healthy, immune compromised and obese subjects, as well as subjects with intestinal disorders, infections and inflammatory disorders. This study revealed no major safety concerns, as the adverse events (AEs) were unrelated, or not suspected to be related, to the probiotic or synbiotic product. In general the study products were well tolerated. Overall, AEs occurred more frequent in the control arm compared to children receiving probiotics and/or synbiotics. Furthermore, the results indicate inadequate reporting and classification of AEs in the majority of the studies. In addition, generalizability of conclusions are greatly limited by the inconsistent, imprecise and potentially incomplete reporting as well as the variation in probiotic strains, dosages, administration regimes, study populations and reported outcomes.
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- Van den Nieuwboer, M., et al.
(author)
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The administration of probiotics and synbiotics in immune compromised adults : is it safe?
- 2015
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In: Beneficial Microbes. - 1876-2883 .- 1876-2891. ; 6:1, s. 3-17
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Journal article (peer-reviewed)abstract
- This study aimed to systematically evaluate safety of probiotics and synbiotics in immune compromised adults (>= 18 years). Safety was analysed using the Common Terminology Clinical Adverse Events (CTCAE version 4.0) classification, thereby providing an update on previous reports using the most recent available clinical data (2008-2013). Safety aspects are represented and related to number of participants per probiotic strain/culture, study duration, dosage, clinical condition and selected afflictions. Analysis of 57 clinical studies indicates that probiotic and/or synbiotic administration in immune compromised adults is safe with regard to the current evaluated probiotic strains, dosages and duration. Individuals were considered immune compromised if HIV-infected, critically ill, underwent surgery or had an organ- or an autoimmune disease. There were no major safety concerns in the study, as none of the serious adverse events (AE)s were related, or suspected to be related, to the probiotic or synbiotic product and the study products were well tolerated. Overall, AEs occurred less frequent in immune compromised subjects receiving probiotics and/or synbiotics compared to the control group. In addition, the results demonstrated a flaw in precise reporting and classification of AE in most studies. Furthermore, generalisability of conclusions are greatly limited by the inconsistent, imprecise and potentially incomplete reporting as well as the variation in probiotic strains, dosages, administration regimes, study populations and reported outcomes. We argue that standardised reporting on adverse events (CTCAE) in 'food' studies should be obligatory, thereby improving reliability of data and re-enforcing the safety profile of probiotics.
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- Li, Biao, et al.
(author)
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Capturing dynamic ligand-to-metal charge transfer with a long-lived cationic intermediate for anionic redox
- 2022
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In: Nature Materials. - : Springer Nature. - 1476-1122 .- 1476-4660. ; 21:10, s. 1165-1174
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Journal article (peer-reviewed)abstract
- Reversible anionic redox reactions represent a transformational change for creating advanced high-energy-density positive-electrode materials for lithium-ion batteries. The activation mechanism of these reactions is frequently linked to ligand-to-metal charge transfer (LMCT) processes, which have not been fully validated experimentally due to the lack of suitable model materials. Here we show that the activation of anionic redox in cation-disordered rock-salt Li1.17Ti0.58Ni0.25O2 involves a long-lived intermediate Ni3+/4+ species, which can fully evolve to Ni2+ during relaxation. Combining electrochemical analysis and spectroscopic techniques, we quantitatively identified that the reduction of this Ni3+/4+ species goes through a dynamic LMCT process (Ni3+/4+–O2− → Ni2+–On−). Our findings provide experimental validation of previous theoretical hypotheses and help to rationalize several peculiarities associated with anionic redox, such as cationic–anionic redox inversion and voltage hysteresis. This work also provides additional guidance for designing high-capacity electrodes by screening appropriate cationic species for mediating LMCT.
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