School-based early intervention for anxiety and depression in older adolescents:A feasibility randomised controlled trial of a self-referral stress management workshop programme (“DISCOVER”)

Introduction Schools may provide a convenient intervention setting for young people with mental health problems generally, as well as for those who are unwilling or unable to access traditional clinic-based mental health services. However, few studies focus on older adolescents, or those from ethnic minority groups. This study aims to assess the feasibility of a brief school-based psychological intervention for self-referred adolescents aged 16–19 years. Methods A two-arm cluster randomised controlled trial was conducted in 10 inner-city schools with block randomisation of schools. The intervention comprised a one-day CBT Stress management programme with telephone follow-up (DISCOVER) delivered by 3 psychology (2 clinical and 1 assistant) staff. The control was a waitlist condition. Primary outcomes were depression (Mood and Feelings Questionnaire; MFQ) and anxiety (Revised Child Anxiety and Depression Scale; RCADS-anxiety subscale). Data were analysed descriptively and quantitatively to assess feasibility. Results 155 students were enrolled and 142 (91.6%) followed up after 3 months. Participants were predominantly female (81%) and the mean age was 17.3 years, with equal numbers enrolled from Year 12 and Year 13. Over half (55%) of students were from ethnic minority groups. Intraclass correlations were low. Variance estimates were calculated to estimate the sample size for a full RCT. Preliminary outcomes were encouraging, with reductions in depression (d = 0.27 CI-0.49 to −0.04, p = 0.021) and anxiety (d = 0.25, CI-0.46 to −0.04, p = 0.018) at follow-up. Conclusions Results support the feasibility of a school-based, self-referral intervention with older adolescents in a definitive future full-scale trial (Trial no. ISRCTN88636606)

Fecal microbiota transfer between young and aged mice reverses hallmarks of the aging gut, eye, and brain

Background: Altered intestinal microbiota composition in later life is associated with inflammaging, declining tissue function, and increased susceptibility to age-associated chronic diseases, including neurodegenerative dementias. Here, we tested the hypothesis that manipulating the intestinal microbiota influences the development of major comorbidities associated with aging and, in particular, inflammation affecting the brain and retina. Methods: Using fecal microbiota transplantation, we exchanged the intestinal microbiota of young (3 months), old (18 months), and aged (24 months) mice. Whole metagenomic shotgun sequencing and metabolomics were used to develop a custom analysis workflow, to analyze the changes in gut microbiota composition and metabolic potential. Effects of age and microbiota transfer on the gut barrier, retina, and brain were assessed using protein assays, immunohistology, and behavioral testing. Results: We show that microbiota composition profiles and key species enriched in young or aged mice are successfully transferred by FMT between young and aged mice and that FMT modulates resulting metabolic pathway profiles. The transfer of aged donor microbiota into young mice accelerates age-associated central nervous system (CNS) inflammation, retinal inflammation, and cytokine signaling and promotes loss of key functional protein in the eye, effects which are coincident with increased intestinal barrier permeability. Conversely, these detrimental effects can be reversed by the transfer of young donor microbiota. Conclusions: These findings demonstrate that the aging gut microbiota drives detrimental changes in the gut–brain and gut–retina axes suggesting that microbial modulation may be of therapeutic benefit in preventing inflammation-related tissue decline in later life. [MediaObject not available: see fulltext.] Graphical abstract: [Figure not available: see fulltext.

Regulation of Enteroendocrine Cell Networks by the Major Human Gut Symbiont Bacteroides thetaiotaomicron

Gut microbes have critical roles in maintaining host physiology, but their effects on epithelial chemosensory enteroendocrine cells (EEC) remain unclear. We investigated the role that the ubiquitous commensal gut bacterium Bacteriodes thetaiotaomicron (Bt) and its major fermentation products, acetate, propionate, and succinate (APS) have in shaping EEC networks in the murine gastrointestinal tract (GIT). The distribution and numbers of EEC populations were assessed in tissues along the GIT by fluorescent immunohistochemistry in specific pathogen free (SPF), germfree (GF) mice, GF mice conventionalized by Bt or Lactobacillus reuteri (Lr), and GF mice administered APS. In parallel, we also assessed the suitability of using intestinal crypt-derived epithelial monolayer cultures for these studies. GF mice up-regulated their EEC network, in terms of a general EEC marker chromogranin A (ChrA) expression, numbers of serotonin-producing enterochromaffin cells, and both hormone-producing K- and L-cells, with a corresponding increase in serum glucagon-like peptide-1 (GLP-1) levels. Bt conventionalization restored EEC numbers to levels in SPF mice with regional specificity; the effects on ChrA and L-cells were mainly in the small intestine, the effects on K-cells and EC cells were most apparent in the colon. By contrast, Lr did not restore EEC networks in conventionalized GF mice. Analysis of secretory epithelial cell monolayer cultures from whole small intestine showed that intestinal monolayers are variable and with the possible exclusion of GIP expressing cells, did not accurately reflect the EEC cell makeup seen in vivo. Regarding the mechanism of action of Bt on EECs, colonization of GF mice with Bt led to the production and accumulation of acetate, propionate and succinate (APS) in the caecum and colon, which when administered at physiological concentrations to GF mice via their drinking water for 10 days mimicked to a large extent the effects of Bt in GF mice. After withdrawal of APS, the changes in some EEC were maintained and, in some cases, were greater than during APS treatment. This data provides evidence of microbiota influences on regulating EEC networks in different regions of the GIT, with a single microbe, Bt, recapitulating its role in a process that may be dependent upon its fermentation products

Fecal microbiota transfer between young and aged mice reverses hallmarks of the aging gut, eye, and brain

Background: Altered intestinal microbiota composition in later life is associated with inflammaging, declining tissue function, and increased susceptibility to age-associated chronic diseases, including neurodegenerative dementias. Here, we tested the hypothesis that manipulating the intestinal microbiota influences the development of major comorbidities associated with aging and, in particular, inflammation affecting the brain and retina. Methods: Using fecal microbiota transplantation, we exchanged the intestinal microbiota of young (3 months), old (18 months), and aged (24 months) mice. Whole metagenomic shotgun sequencing and metabolomics were used to develop a custom analysis workflow, to analyze the changes in gut microbiota composition and metabolic potential. Effects of age and microbiota transfer on the gut barrier, retina, and brain were assessed using protein assays, immunohistology, and behavioral testing. Results: We show that microbiota composition profiles and key species enriched in young or aged mice are successfully transferred by FMT between young and aged mice and that FMT modulates resulting metabolic pathway profiles. The transfer of aged donor microbiota into young mice accelerates age-associated central nervous system (CNS) inflammation, retinal inflammation, and cytokine signaling and promotes loss of key functional protein in the eye, effects which are coincident with increased intestinal barrier permeability. Conversely, these detrimental effects can be reversed by the transfer of young donor microbiota. Conclusions: These findings demonstrate that the aging gut microbiota drives detrimental changes in the gut–brain and gut–retina axes suggesting that microbial modulation may be of therapeutic benefit in preventing inflammation-related tissue decline in later life

Comparing What to What, on What Scale? The Impact of Item Comparisons and Reference Points in Communicating Risk and Uncertainty ; Reference Points

The mandated public availability of individual hospital's audit data for children's heart surgery in the UK creates a challenging scenario for communicating these complex and sensitive data to diverse audiences. On the basis of this scenario, we conducted three experiments with the aim of understanding how best to help lay people understand these data and the practical goal of improving the public presentation of these data. The experiments compared different outcome measures for displaying the survival rate (percentage scale versus the ratio of the predicted/observed rates) and presentation formats (individual hospital versus all hospitals shown) for outcomes data presented relative to prediction intervals generated by a risk model that adjusts for case mix. Our data highlight how easily inappropriate comparisons can influence evaluations of complex data: for instance, both a survival ratio of 1 and the presence of other hospitals seemingly provided reference points that resulted in inappropriately harsh evaluations of some hospitals. By drawing on evaluability theory, we demonstrate how to enhance people's understanding of these complex data while also discouraging inappropriate comparisons, which has implications for communicating risk and uncertainty and for choice architecture design in a range of contexts

Exploring the feasibility and acceptability of a school-based self-referral intervention for emotional difficulties in older adolescents: qualitative perspectives from students and school staff

BACKGROUND: Adolescents with emotional difficulties need accessible, acceptable and evidence-based mental health interventions. Self-referral workshops (DISCOVER workshops) were offered to stressed 16- to 19-year olds in 10 Inner London schools. METHOD: Semistructured interviews were conducted with three groups of participants: students who attended a 1-day workshop (n = 15); students who initially showed interest in the DISCOVER workshop programme, but decided not to take part (n = 9); and school staff who helped organise the programme in their schools (n = 10). Students were purposively sampled to ensure that those from Black and minority ethnic (BME) backgrounds were represented. Data were analysed using thematic analysis. RESULTS: The accounts generally indicate that the delivery and evaluation of this intervention is perceived as feasible and acceptable. Students, including those from BME backgrounds, described the setting as suitable and reported that the workshop helped them develop new understandings of stress and how to handle it. They expressed a preference for engaging and interactive activities, and valued a personalised approach to workshop provision. School staff felt that the workshop was in line with school values. They described some logistical barriers to providing the workshops in school settings, and expressed a desire for more information about the workshop in order to provide follow-up support. The main reason students gave for nonparticipation was limited time. CONCLUSIONS: Findings are discussed in relation to increasing the feasibility of implementing school-based psychological interventions and the value of providing access to mental health support in schools

Understanding Children’s Heart Surgery Data: A Cross-Disciplinary Approach to Codevelop a Website

Risk-adjusted survival statistics after children's heart surgery are published annually in the United Kingdom. Interpreting these statistics is difficult, and better resources about how to interpret survival data are needed. Here we describe how a multidisciplinary team of mathematicians, psychologists, and a charity worked with parents of heart surgery children and other users to codevelop online resources to present survival outcomes. Early and ongoing involvement of users was crucial and considerably changed the content, scope, and look of the website, and the formal psychology experiments provided deeper insight. The website http://childrensheartsurgery.info/ was launched in June 2016 to very positive reviews

The use of a multicellular in vitro model to investigate uptake and migration of bacterial extracellular vesicles derived from the human gut commensal Bacteroides thetaiotaomicron

Abstract Bacterial extracellular vesicles (BEVs) are increasingly seen as key signalling mediators between the gut microbiota and the host. Recent studies have provided evidence of BEVs ability to transmigrate across cellular barriers to elicit responses in other tissues, such as the central nervous system (CNS). Here we use a combination of single‐, two‐ and three‐cell culture systems to demonstrate the transmigration of Bacteroides thetaiotaomicron derived BEVs (Bt‐BEVs) across gut epithelium and blood brain barrier (BBB) endothelium, and their subsequent acquisition and downstream effects in neuronal cells. Bt‐BEVs were shown to traffic to the CNS in vivo after intravenous administration to mice, and in multi‐cell in vitro culture systems to transmigrate across gut epithelial and BBB endothelial cell barriers, where they were acquired by both microglia and immature neuronal cells. No significant activation/inflammatory effects were induced in non‐differentiated neurons, in contrast to that observed in microglia cells, although this was notably less than that induced by lipopolysaccharide (LPS). Overall, our findings provide evidence for transmigration of Bt‐BEVs across gut‐epithelial and BBB endothelial cell barriers in vivo and in vitro, and their downstream responses in neural cells. This study sheds light onto how commensal bacteria‐derived BEV transport across the gut‐brain axis and can be exploited for the development of targeted drug delivery