Moderate variations in the human diet impact the gut microbiota in humanized mice.

AIM: Drastic diet interventions have been shown to promote rapid and significant compositional changes of the gut microbiota, but the impact of moderate diet variations is less clear. Here, we aimed to clarify the impact of moderate diet variations that remain within the spectrum of the habitual human diet on gut microbiota composition. METHODS: We performed a pilot diet intervention where five healthy volunteers consumed a vegetarian ready-made meal for three days to standardize dietary intake before switching to a meat-based ready-made western-style meal and high sugar drink for two days. We performed 16S rRNA sequencing from daily fecal sampling to assess gut microbiota changes caused by the intervention diet. Furthermore, we used the volunteers' fecal samples to colonize germ-free mice that were fed the same sterilized diets to study the effect of a moderate diet intervention on the gut microbiota in a setting of reduced interindividual variation. RESULTS: In the human intervention, we found that fecal microbiota composition varied between and within individuals regardless of diet. However, when we fed the same diets to mice colonized with the study participants' feces, we observed significant, often donor-specific, changes in the mouse microbiota following this moderate diet intervention. CONCLUSION: Moderate variations in the habitual human diet have the potential to alter the gut microbiota. Feeding humanized mice human diets may facilitate our understanding of individual human gut microbiota responses to moderate dietary changes and help improve individualized interventions.

Modelling arts professionals' wellbeing and career intentions within the context of COVID-19.

The COVID-19 pandemic had a substantial effect on the creative and cultural industries in the United Kingdom (UK), as seen in our first snapshot of the HEartS Professional Survey (April-June 2020, Phase 1, N = 358). By analysing data collected one year later (April-May 2021, Phase 2, N = 685), the aims of the current study are to trace the contributors to (1) arts professionals' mental and social wellbeing and (2) their expectations of staying in the arts. Findings show that artists continued to experience challenges in terms of finances, and mental and social wellbeing. Over half of the respondents reported financial hardship (59%), and over two thirds reported being lonelier (64%) and having increased anxiety (71%) than before the pandemic. Hierarchical multiple linear regression models, using the Mental Health Continuum-Short Form, Center for Epidemiologic Studies Depression Scale, Social Connectedness Scale, and Three-Item Loneliness Scale as outcome variables, indicate that perceived financial hardship continued to be associated with higher depression and loneliness scores. As in our first study, more physical activity before lockdown was associated with higher wellbeing and social connectedness scores, and higher self-rated health scores were associated with higher wellbeing and lower depression scores. Similarly, increases in physical activity during lockdown, as well as older age, were still associated with higher wellbeing and social connectedness scores and with lower depression and loneliness scores. An ordinal logistic regression model indicated three contributors to artists' professional expectations of remaining in the arts: greater proportion of income from the arts pre-pandemic, continued maintenance of skills, and greater proportion of freelance work. The results suggest that the wellbeing patterns observed at the start of the pandemic remained consistent a year on. They point to possible strategies to support wellbeing and underline the importance of finances for expectations of remaining in arts professions.

Feasibility, clinical efficacy, and well-being outcomes of an online singing intervention for postnatal depression in the UK: SHAPER-PNDO, a single-arm clinical trial.

BACKGROUND: Postnatal depression (PND) affects over 12% of mothers, with numbers rising during COVID-19. Singing groups can support mothers with PND; however, online delivery has never been evaluated. SHAPER-PNDO, a single-arm clinical trial, evaluated the feasibility, clinical efficacy, and well-being outcomes of a 6-week online version of Breathe Melodies for Mums (M4M) singing intervention developed for mothers with PND during COVID-19 lockdowns. METHODS: The primary objective of this study was to assess the feasibility of a group online singing intervention for new mothers with postnatal depression. This was ascertained through recruitment rates, study retention rates, attendance rates to the singing sessions, and study completion rates. The secondary objective of the study was to assess the clinical efficacy and well-being outcomes of the singing intervention. Specifically, we measured change in Edinburgh Postnatal Depression Scale (EPDS), State-Trait Anxiety Inventory (STAI), Perceived Stress Scale (PSS), and Office for National Statistics Wellbeing Scale (ONS) scores from baseline to end-of-intervention (week 6); follow-up assessments were completed at weeks 3, 16, and 32. Mothers were eligible if they scored ≥10 on the baseline EPDS. RESULTS: Eighty-seven percent of the 37 recruited mothers completed the study, attending, on average, 5 of the 6 group singing sessions. With regard to secondary outcomes, at end-of-treatment, mothers experienced significant reductions in depression (EPDS, 16.6 ± 3.7 to 11.2 ± 5.3, 95% CI [0.79,1.65]), anxiety (STAI-S, 48.4 ± 27.1 to 41.7 ± 26.8, 95% CI [4.96, 17.65]) and stress (PSS, 29.0 ± 5.7 to 19.7 ± 5.3, 95% CI [1.33, 7.07]); and, furthermore, significant improvements in life satisfaction (ONS, 50.5 ± 23.0 to 72.8 ± 11.7, 95% CI [- 39.86, - 4.64]) and feelings of worthwhileness (ONS, 51.7 ± 30.4 to 78.6 ± 15.1, 95% CI [- 52.79, - 0.85]). Reduction on the EPDS correlated with a reduction on the BDI and the STAI-S and maternal childhood maltreatment was predictive of a smaller treatment response. CONCLUSIONS: M4M online was feasible to mothers who partook in the programme. Furthermore, M4M online supports the mental health and well-being of new mothers experiencing PND, especially when barriers to in-person treatment are present. TRIAL REGISTRATION: ClinicalTrials.gov NCT04857593 . Registered 22 April 2021, retrospectively registered.

Low-grade intestinal inflammation two decades after pelvic radiotherapy.

BACKGROUND: Radiotherapy is effective in the treatment of cancer but also causes damage to non-cancerous tissue. Pelvic radiotherapy may produce chronic and debilitating bowel symptoms, yet the underlying pathophysiology is still undefined. Most notably, although pelvic radiotherapy causes an acute intestinal inflammation there is no consensus on whether the late-phase pathophysiology contains an inflammatory component or not. To address this knowledge gap, we examined the potential presence of a chronic inflammation in mucosal biopsies from irradiated pelvic cancer survivors. METHODS: We biopsied 24 cancer survivors two to 20 years after pelvic radiotherapy, and four non-irradiated controls. Using tandem mass tag (TMT) mass spectrometry and mRNA sequencing (mRNA-seq), we charted proteomic and transcriptomic profiles of the mucosal tissue previously exposed to a high or a low/no dose of radiation. Changes in the immune cell populations were determined with flow cytometry. The integrity of the protective mucus layers were determined by permeability analysis and 16S rRNA bacterial detection. FINDINGS: 942 proteins were differentially expressed in mucosa previously exposed to a high radiation dose compared to a low radiation dose. The data suggested a chronic low-grade inflammation with neutrophil activity, which was confirmed by mRNA-seq and flow cytometry and further supported by findings of a weakened mucus barrier with bacterial infiltration. INTERPRETATION: Our results challenge the idea that pelvic radiotherapy causes an acute intestinal inflammation that either heals or turns fibrotic without progression to chronic inflammation. This provides a rationale for exploring novel strategies to mitigate chronic bowel symptoms in pelvic cancer survivors. FUNDING: This study was supported by the King Gustav V Jubilee Clinic Cancer Foundation (CB), The Adlerbertska Research Foundation (CB), The Swedish Cancer Society (GS), The Swedish State under the ALF agreement (GS and CB), Mary von Sydow's foundation (MA and VP).

Evolution of age-related mutation-driven clonal haematopoiesis over 20 years is associated with metabolic dysfunction in obesity.

BACKGROUND: Haematopoietic clones caused by somatic mutations with ≥2% variant allele frequency (VAF) increase with age and are linked to risk of haematological malignancies and cardiovascular disease. Recent observations suggest that smaller clones (VAF<2%) are also associated with adverse outcomes. Our aims were to determine the prevalence of clonal haematopoiesis driven by clones of variable sizes in individuals with obesity treated by usual care or bariatric surgery (a treatment that improves metabolic status), and to examine the expansion of clones in relation to age and metabolic dysregulation over up to 20 years. METHODS: Clonal haematopoiesis-driver mutations (CHDMs) were identified in blood samples from participants of the Swedish Obese Subjects intervention study. Using an ultrasensitive assay, we analysed single-timepoint samples from 1050 individuals treated by usual care and 841 individuals who had undergone bariatric surgery, and multiple-timepoint samples taken over 20 years from a subset (n = 40) of the individuals treated by usual care. FINDINGS: In this explorative study, prevalence of CHDMs was similar in the single-timepoint usual care and bariatric surgery groups (20.6% and 22.5%, respectively, P = 0.330), with VAF ranging from 0.01% to 31.15%. Clone sizes increased with age in individuals with obesity, but not in those who underwent bariatric surgery. In the multiple-timepoint analysis, VAF increased by on average 7% (range -4% to 24%) per year and rate of clone growth was negatively associated with HDL-cholesterol (R = -0.68, 1.74 E-04). INTERPRETATION: Low HDL-C was associated with growth of haematopoietic clones in individuals with obesity treated by usual care. FUNDING: The Swedish Research Council, The Swedish state under an agreement between the Swedish government and the county councils, the ALF (Avtal om Läkarutbildning och Forskning) agreement, The Swedish Heart-Lung Foundation, The Novo Nordisk Foundation, The European Research Council, The Netherlands Organisation for Scientific Research.

Exploring the experiences of loneliness in adults with mental health problems: A participatory qualitative interview study.

BACKGROUND: Loneliness is associated with many mental health conditions, as both a potential causal and an exacerbating factor. Richer evidence about how people with mental health problems experience loneliness, and about what makes it more or less severe, is needed to underpin research on strategies to help address loneliness. METHODS: Our aim was to explore experiences of loneliness, as well as what helps address it, among a diverse sample of adults living with mental health problems in the UK. We recruited purposively via online networks and community organisations, with most interviews conducted during the COVID-19 pandemic. Qualitative semi-structured interviews were conducted with 59 consenting participants face-to-face, by video call or telephone. Researchers with relevant lived experience were involved at all stages, including design, data collection, analysis and writing up of results. FINDINGS: Analysis led to identification of four overarching themes: 1. What the word "lonely" meant to participants, 2. Connections between loneliness and mental health, 3. Contributory factors to continuing loneliness, 4. Ways of reducing loneliness. Central aspects of loneliness were lack of meaningful connections with others and lack of a sense of belonging to valued groups and communities. Some drivers of loneliness, such as losses and transitions, were universal, but specific links were also made between living with mental health problems and being lonely. These included direct effects of mental health symptoms, the need to withdraw to cope with mental health problems, and impacts of stigma and poverty. CONCLUSIONS: The multiplicity of contributors to loneliness that we identified, and of potential strategies for reducing it, suggest that a variety of approaches are relevant to reducing loneliness among people with mental health problems, including peer support and supported self-help, psychological and social interventions, and strategies to facilitate change at community and societal levels. The views and experiences of adults living with mental health problems are a rich source for understanding why loneliness is frequent in this context and what may address it. Co-produced approaches to developing and testing approaches to loneliness interventions can draw on this experiential knowledge.

Cardiomyocyte-specific PCSK9 deficiency compromises mitochondrial bioenergetics and heart function.

AIMS: Pro-protein convertase subtilisin-kexin type 9 (PCSK9), which is expressed mainly in the liver and at low levels in the heart, regulates cholesterol levels by directing low-density lipoprotein receptors to degradation. Studies to determine the role of PCSK9 in the heart are complicated by the close link between cardiac function and systemic lipid metabolism. Here, we sought to elucidate the function of PCSK9 specifically in the heart by generating and analysing mice with cardiomyocyte-specific Pcsk9 deficiency (CM-Pcsk9-/- mice) and by silencing Pcsk9 acutely in a cell culture model of adult cardiomyocyte-like cells. METHODS AND RESULTS: Mice with cardiomyocyte-specific deletion of Pcsk9 had reduced contractile capacity, impaired cardiac function, and left ventricular dilatation at 28 weeks of age and died prematurely. Transcriptomic analyses revealed alterations of signalling pathways linked to cardiomyopathy and energy metabolism in hearts from CM-Pcsk9-/- mice vs. wild-type littermates. In agreement, levels of genes and proteins involved in mitochondrial metabolism were reduced in CM-Pcsk9-/- hearts. By using a Seahorse flux analyser, we showed that mitochondrial but not glycolytic function was impaired in cardiomyocytes from CM-Pcsk9-/- mice. We further showed that assembly and activity of electron transport chain (ETC) complexes were altered in isolated mitochondria from CM-Pcsk9-/- mice. Circulating lipid levels were unchanged in CM-Pcsk9-/- mice, but the lipid composition of mitochondrial membranes was altered. In addition, cardiomyocytes from CM-Pcsk9-/- mice had an increased number of mitochondria-endoplasmic reticulum contacts and alterations in the morphology of cristae, the physical location of the ETC complexes. We also showed that acute Pcsk9 silencing in adult cardiomyocyte-like cells reduced the activity of ETC complexes and impaired mitochondrial metabolism. CONCLUSION: PCSK9, despite its low expression in cardiomyocytes, contributes to cardiac metabolic function, and PCSK9 deficiency in cardiomyocytes is linked to cardiomyopathy, impaired heart function, and compromised energy production.

Accelerated QT adaptation following atropine-induced heart rate increase in LQT1 patients versus healthy controls: A sign of disturbed hysteresis.

Hysteresis, a ubiquitous regulatory phenomenon, is a salient feature of the adaptation of ventricular repolarization duration to heart rate (HR) change. We therefore compared the QT interval adaptation to rapid HR increase in patients with the long QT syndrome type 1 (LQT1) versus healthy controls because LQT1 is caused by loss-of-function mutations affecting the repolarizing potassium channel current IKs , presumably an important player in QT hysteresis. The study was performed in an outpatient hospital setting. HR was increased in LQT1 patients and controls by administering an intravenous bolus of atropine (0.04 mg/kg body weight) for 30 s. RR and QT intervals were recorded by continuous Frank vectorcardiography. Atropine induced transient expected side effects but no adverse arrhythmias. There was no difference in HR response (RR intervals) to atropine between the groups. Although atropine-induced ΔQT was 48% greater in 18 LQT1 patients than in 28 controls (p < 0.001), QT adaptation was on average 25% faster in LQT1 patients (measured as the time constant τ for the mono-exponential function and the time for 90% of ΔQT; p < 0.01); however, there was some overlap between the groups, possibly a beta-blocker effect. The shorter QT adaptation time to atropine-induced HR increase in LQT1 patients on the group level corroborates the importance of IKs in QT adaptation hysteresis in humans and shows that LQT1 patients have a disturbed ultra-rapid cardiac memory. On the individual level, the QT adaptation time possibly reflects the effect-size of the loss-of-function mutation, but its clinical implications need to be shown.

Online singing interventions for postnatal depression in times of social isolation: a feasibility study protocol for the SHAPER-PNDO single-arm trial.

BACKGROUND: Postnatal depression (PND) affects 13% of new mothers, with numbers rising during the COVID-19 pandemic. Despite this prevalence, many women have difficulty with or hesitancy towards accessing pharmacological and/or psychological interventions. Group-based mother-baby activities, however, have a good uptake, with singing improving maternal mental health and the mother-infant relationship. The recent lockdowns highlight the importance of adapting activities to an online platform that is wide-reaching and accessible. AIMS: The SHAPER-PNDO study will primarily analyse the feasibility of a 6-week online singing intervention, Melodies for Mums (M4M), for mothers with PND who are experiencing barriers to treatment. The secondary aim of the SHAPER-PNDO study will be to analyse the clinical efficacy of the 6-week M4M intervention for symptoms of postnatal depression. METHODS: A total of 120 mothers and their babies will be recruited for this single-arm study. All dyads will attend 6 weekly online singing sessions, facilitated by Breathe Arts Health Research. Assessments will be conducted on Zoom at baseline and week 6, with follow-ups at weeks 16 and 32, and will contain interviews for demographics, mental health, and social circumstances, and biological samples will be taken for stress markers. Qualitative interviews will be undertaken to understand the experiences of women attending the sessions and the facilitators delivering them. Finally, data will be collected on recruitment, study uptake and attendance of the programme, participant retention, and acceptability of the intervention. DISCUSSION: The SHAPER-PNDO study will focus on the feasibility, alongside the clinical efficacy, of an online delivery of M4M, available to all mothers with PND. We hope to provide a more accessible, effective treatment option for mothers with PND that can be available both during and outside of the pandemic for mothers who would otherwise struggle to attend in-person sessions, as well as to prepare for a subsequent hybrid RCT. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04857593 . Registered retrospectively on 22 April 2021. The first participants were recruited on 27 January 2021, and the trial is ongoing.

The future of the cultural workforce: Perspectives from early career arts professionals on the challenges and future of the cultural industries in the context of COVID-19.

The COVID-19 pandemic has had a profound impact on the arts sector, disrupting livelihoods and professional networks and accentuating the instability that is common for creative workers. Gaps in support for grassroots organisations and freelance workers have highlighted structural inequalities within the industry, and the significant challenges for individual workers in the early stages of their career. Yet, the pandemic has also emphasised the importance of the arts as a community resource and its role in supporting wellbeing and togetherness. This qualitative study explored the experiences of the pandemic for early career arts workers, focusing on its impacts upon their livelihoods and how it has shaped their future career directions. Sixteen arts and cultural workers across a variety of sectors including theatre, film, circus, music, and literature participated in solo, semi-structured interviews during April-June 2021. Thematic analysis identified three overarching themes: (i) 'Pandemic precarity and creative practice', (ii) 'PostCOVID I: Inclusivity and diversifying audiences', and (iii) 'PostCOVID II: Adapting, developing, and disrupting cultural practices'. Overall, the experiences capture an early career workforce that, while committed and engaged with their creative practice, also seeks a more equitable, fairer, and diverse industry that protects artists and engages more flexibly with broader audiences.

Dynamics of the normal gut microbiota: A longitudinal one-year population study in Sweden.

Temporal dynamics of the gut microbiota potentially limit the identification of microbial features associated with health status. Here, we used whole-genome metagenomic and 16S rRNA gene sequencing to characterize the intra- and inter-individual variations of gut microbiota composition and functional potential of a disease-free Swedish population (n = 75) over one year. We found that 23% of the total compositional variance was explained by intra-individual variation. The degree of intra-individual compositional variability was negatively associated with the abundance of Faecalibacterium prausnitzii (a butyrate producer) and two Bifidobacterium species. By contrast, the abundance of facultative anaerobes and aerotolerant bacteria such as Escherichia coli and Lactobacillus acidophilus varied extensively, independent of compositional stability. The contribution of intra-individual variance to the total variance was greater for functional pathways than for microbial species. Thus, reliable quantification of microbial features requires repeated samples to address the issue of intra-individual variations of the gut microbiota.

Study protocol: randomised controlled hybrid type 2 trial evaluating the scale-up of two arts interventions for postnatal depression and Parkinson's disease.

INTRODUCTION: Research on the benefits of 'arts' interventions to improve individuals' physical, social and psychological well-being is growing, but evidence on implementation and scale-up into health and social care systems is lacking. This protocol reports the SHAPER-Implement programme (Scale-up of Health-Arts Programmes Effectiveness-Implementation Research), aimed at studying the impact, implementation and scale-up of: Melodies for Mums (M4M), a singing intervention for postnatal depression; and Dance for Parkinson's (PD-Ballet) a dance intervention for Parkinson's disease. We examine how they could be embedded in clinical pathways to ensure their longer-term sustainability. METHODS AND ANALYSIS: A randomised two-arm effectiveness-implementation hybrid type 2 trial design will be used across M4M/PD-Ballet. We will assess the implementation in both study arms (intervention vs control), and the cost-effectiveness of implementation. The design and measures, informed by literature and previous research by the study team, were refined through stakeholder engagement. Participants (400 in M4M; 160 in PD-Ballet) will be recruited to the intervention or control group (2:1 ratio). Further implementation data will be collected from stakeholders involved in referring to, delivering or supporting M4M/PD-Ballet (N=25-30 for each intervention).A mixed-methods approach (surveys and semi-structured interviews) will be employed. 'Acceptability' (measured by the 'Acceptability Intervention Measure') is the primary implementation endpoint for M4M/PD-Ballet. Relationships between clinical and implementation outcomes, implementation strategies (eg, training) and outcomes will be explored using generalised linear mixed models. Qualitative data will assess factors affecting the acceptability, feasibility and appropriateness of M4M/PD-Ballet, implementation strategies and longer-term sustainability. Costs associated with implementation and future scale-up will be estimated. ETHICS AND DISSEMINATION: SHAPER-PND (the M4M trial) and SHAPER-PD (the PD trial) are approved by the West London and GTAC (20/PR/0813) and the HRA and Health and Care Research Wales (REC Reference: 20/WA/0261) Research Ethics Committees. Study findings will be disseminated through scientific peer-reviewed journals and scientific conferences. TRIAL REGISTRATION NUMBERS: Both trials are registered with NIH US National Library of Medicine, ClinicalTrials.gov. The trial registration numbers, URLs of registry records, and dates of registration are: (1) PD-Ballet: URL: NCT04719468 (https://eur03.safelinks.protection. OUTLOOK: com/?url=https%3A%2F%2Fwww.clinicaltrials.gov%2Fct2%2Fshow%2FNCT04719468%3Fterm%3DNCT04719468%26draw%3D2%26rank%3D1&data=04%7C01%7Crachel.davis%40kcl.ac.uk%7C11a7c5142782437919f808d903111449%7C8370cf1416f34c16b83c724071654356%7C0%7C0%7C6375441942616) (date of registration: 22 Jan 2021). (2) Melodies for Mums: NCT04834622 (https://clinicaltrials.gov/ct2/show/NCT04834622?term=shaper-pnd&draw=2&rank=1) (date of registration: 8 Apr 2021).

SHAPER-PND trial: clinical effectiveness protocol of a community singing intervention for postnatal depression.

INTRODUCTION: Postnatal depression (PND) affects approximately 13% of new mothers. Community-based activities are sought after by many mothers, especially mothers that prefer not to access pharmacological or psychological interventions. Singing has shown positive effects in maternal mood and mother-child bonding. The Scaling-Up Health-Arts Programmes: Implementation and Effectiveness Research-Postnatal Depression study will analyse the clinical and implementation effectiveness of 10-week singing sessions for PND in new mothers. This protocol paper will focus on the clinical effectiveness of this trial. METHODS AND ANALYSIS: A total of 400 mothers with PND (with a score of at least 10 on the Edinburgh Postnatal Depression Scale) and their babies will be recruited for this hybrid type II randomised controlled trial. The intervention group will attend 10 weekly singing sessions held at community venues or online, facilitated by the arts organisation, Breathe Arts Health Research (Breathe). A control group will be encouraged to attend non-singing sessions in the community or online for 10 weeks. A package of assessments will be collected from participants for clinical, mechanistic and implementation outcomes, at different stages of the trial. Clinical assessments will include questionnaires and interviews for demographics, mental health and social measures, together with biological samples for measurement of stress markers; the study visits are at baseline, week 6 (mid-trial) and week 10 (end of trial), with follow ups at weeks 20 and 36. Multiple imputation will be used to deal with possible missing data and multivariable models will be fitted to assess differences between groups in the outcomes of the study. ETHICS AND DISSEMINATION: Ethical approval has been granted by the London-West London and GTAC Research Ethics Committee, REC reference: 20/PR/0813. TRIAL REGISTRATION NUMBER: NCT04834622; Pre-results.

Arts engagement supports social connectedness in adulthood: findings from the HEartS Survey.

BACKGROUND: Loneliness is a public health challenge, associated with premature mortality and poorer health outcomes. Social connections can mitigate against loneliness, and there is evidence that the arts can support social connectedness. However, existing research on the arts and social connectedness is limited by focus on particular age groups and arts activities, as well as a reliance on typically small-scale studies. METHODS: This study reports survey data from 5892 adults in the United Kingdom, closely matched to the national profile in terms of sociodemographic and economic characteristics. It investigates the extent to which arts engagement is perceived to be linked with feelings of social connectedness, which forms of arts engagement are reported as most connecting, and how. Data were collected via the HEartS Survey, a newly designed tool to capture arts engagement in the United Kingdom and its associations with social and mental health outcomes. Demographic and quantitative data, pertaining to the extent to which arts engagement is perceived to be linked with social connectedness, were analysed descriptively. Qualitative data pertaining to respondents' perceptions of how arts engagement is linked with feelings of social connectedness were analysed using inductive thematic analysis. RESULTS: Results demonstrated that the majority of respondents (82%) perceive their arts engagement to be linked with feelings of social connectedness at least some of the time. The forms of arts engagement most linked with feelings of social connectedness were attending a live music performance, watching a live theatre performance, and watching a film or drama at the cinema or other venue. Four overarching themes characterise how arts engagement is perceived to facilitate feelings of social connectedness: social opportunities, sharing, commonality and belonging, and collective understanding. CONCLUSIONS: The findings suggest that arts engagement can support social connectedness among adults in the UK through multiple pathways, providing large-scale evidence of the important role that the arts can play in supporting social public health.

Arts engagement trends in the United Kingdom and their mental and social wellbeing implications: HEartS Survey.

Evidence on the role of the arts in promoting health and wellbeing has grown over the last two decades. In the United Kingdom, studies using secondary data sources have documented temporal variations in levels of arts engagement in the population, its determinants and its mental wellbeing implications. However, arts engagement is often characterized by prioritizing "high-brow" art forms. In this article, we introduce the HEartS Survey, a tool that aims to increase the balance between inclusivity and brevity of existing arts engagement measures and to focus specifically on the connection between arts engagement and social wellbeing. We explore trends in participatory and receptive engagement with literary, visual, performing, crafts and decorative arts among 5,338 adults in the UK in 2018-2019 using summative engagement scores and cluster analysis. Regression models, adjusted for demographic, socioeconomic, health, and social covariates, examine correlations between arts engagement and psychological and social wellbeing measures. Over 97% of respondents reported engagement in one or more arts activities at least once during 2018-2019, with reading and listening to music being the most popular activities. Arts engagement grouped into three distinct clusters: 19.8% constituted "low engagers" whose main source of engagement was occasional reading; 44.4% constituted "receptive consumers" who read and listened to music frequently and engaged with popular receptive arts activities such as cinema, live music, theater, exhibitions, and museums; and 35.8% constituted "omnivores" who frequently engaged in almost all arts activities. In agreement with existing studies, more arts engagement was associated with higher levels of wellbeing, social connectedness, and lower odds of intense social loneliness. In contrast, we found a positive association between more arts engagement, depression, and intense emotional loneliness for the most highly engaged omnivores. We conclude that arts engagement in the population forms specific profiles with distinct characteristics and consider implications for mental and social wellbeing.

Microbial Imidazole Propionate Affects Responses to Metformin through p38γ-Dependent Inhibitory AMPK Phosphorylation.

Metformin is the first-line therapy for type 2 diabetes, but there are large inter-individual variations in responses to this drug. Its mechanism of action is not fully understood, but activation of AMP-activated protein kinase (AMPK) and changes in the gut microbiota appear to be important. The inhibitory role of microbial metabolites on metformin action has not previously been investigated. Here, we show that concentrations of the microbial metabolite imidazole propionate are higher in subjects with type 2 diabetes taking metformin who have high blood glucose. We also show that metformin-induced glucose lowering is not observed in mice pretreated with imidazole propionate. Furthermore, we demonstrate that imidazole propionate inhibits AMPK activity by inducing inhibitory AMPK phosphorylation, which is dependent on imidazole propionate-induced basal Akt activation. Finally, we identify imidazole propionate-activated p38γ as a novel kinase for Akt and demonstrate that p38γ kinase activity mediates the inhibitory action of imidazole propionate on metformin.

How Participatory Music Engagement Supports Mental Well-being: A Meta-Ethnography.

Participatory music engagement has the capacity to support well-being. Yet, there is little research that has scrutinized the processes through which music has an effect. In this meta-ethnography [PROSPERO CRD42019130164], we conducted a systematic search of 19 electronic databases and a critical appraisal to identify 46 qualitative studies reporting on participants' subjective views of how participatory music engagement supports their mental well-being. Synthesis of first-order and second-order interpretations using thematic coding resulted in four third-order pathways that account for how participatory music engagement supports mental well-being: managing and expressing emotions, facilitating self-development, providing respite, and facilitating connections. Our interpretation suggests that people benefit from participatory music engagement by engaging with specific and multiple processes that meet their individual needs and circumstances. These findings inform research directions within the field of music and well-being, as well as guiding the development and delivery of future music interventions.

The Gut Microbiota in Prediabetes and Diabetes: A Population-Based Cross-Sectional Study.

The link between the gut microbiota and type 2 diabetes (T2D) warrants further investigation because of known confounding effects from antidiabetic treatment. Here, we profiled the gut microbiota in a discovery (n = 1,011) and validation (n = 484) cohort comprising Swedish subjects naive for diabetes treatment and grouped by glycemic status. We observed that overall gut microbiota composition was altered in groups with impaired glucose tolerance, combined glucose intolerance and T2D, but not in those with impaired fasting glucose. In addition, the abundance of several butyrate producers and functional potential for butyrate production were decreased both in prediabetes and T2D groups. Multivariate analyses and machine learning microbiome models indicated that insulin resistance was strongly associated with microbial variations. Therefore, our study indicates that the gut microbiota represents an important modifiable factor to consider when developing precision medicine approaches for the prevention and/or delay of T2D.

Fit to Perform: A Profile of Higher Education Music Students' Physical Fitness.

The physical demands of music making are well acknowledged, but understanding of musicians' physical and fitness profiles is nonetheless limited, especially those of advanced music students who are training to enter music's competitive professional landscape. To gain insight into how physical fitness is associated with music making, this study investigated music students' fitness levels on several standardized indicators. Four hundred and eighty three students took part in a fitness screening protocol that included measurements of lung function, flexibility (hypermobility, shoulder range of motion, sit and reach), strength and endurance (hand grip, plank, press-up), and sub-maximal cardiovascular fitness (3-min step test), as well as self-reported physical activity (IPAQ-SF). Participants scored within age-appropriate ranges on lung function, shoulder range of motion, grip strength, and cardiovascular fitness. Their results for the plank, press-up, and sit and reach were poor by comparison. Reported difficulty (22%) and pain (17%) in internal rotation of the right shoulder were also found. Differences between instrument groups and levels of study were observed on some measures. In particular, brass players showed greater lung function and grip strength compared with other groups, and postgraduate students on the whole were able to maintain the plank for longer but also demonstrated higher hypermobility and lower lung function and cardiovascular fitness than undergraduate students. Seventy-nine percent of participants exceeded the minimum recommended weekly amount of physical activity, but this was mostly based on walking activities. Singers were the most physically active group, and keyboard players, composers, and conductors were the least active. IPAQ-SF scores correlated positively with lung function, sit and reach, press-up and cardiovascular fitness suggesting that, in the absence of time and resources to carry out comprehensive physical assessments, this one measure alone can provide useful insight into musicians' fitness. The findings show moderate levels of general health-related fitness, and we discuss whether moderate fitness is enough for people undertaking physically and mentally demanding music making. We argue that musicians could benefit from strengthening their supportive musculature and enhancing their awareness of strength imbalances.

The Effects of COVID-19 Lockdown 1.0 on Working Patterns, Income, and Wellbeing Among Performing Arts Professionals in the United Kingdom (April-June 2020).

This article reports data collected from 385 performing arts professionals using the HEartS Professional Survey during the COVID-19 Lockdown 1.0 in the United Kingdom. Study 1 examined characteristics of performing arts professionals' work and health, and investigated how these relate to standardized measures of wellbeing. Study 2 examined the effects of the lockdown on work and wellbeing in the respondents' own words. Findings from Study 1 indicate a substantial reduction in work and income. 53% reported financial hardship, 85% reported increased anxiety, and 63% reported being lonelier than before the crisis. 61% sought support on finances while only 45% did so on health and wellbeing. Multiple regression analyses, using the Mental Health Continuum-Short Form, Center for Epidemiologic Studies Depression Scale, Social Connectedness Scale, and Three-Item Loneliness Scale as outcome variables, indicate that perceived financial hardship was associated with lower wellbeing and higher depression and loneliness scores. Higher self-rated health was associated with higher wellbeing and lower depression scores. More physical activity before lockdown was associated with higher wellbeing and social connectedness scores, as well as lower loneliness scores, and an increase in physical activity during lockdown compared with before, as well as older age, were associated with higher wellbeing and social connectedness scores, and lower depression and loneliness scores. Thematic inductive analysis of 341 open responses in Study 2 identified five overarching themes characterizing the effects of Lockdown 1.0: lost or uncertain work and income, including canceled work, financial concerns, and uncertainties for the future; constraints of lockdown working, including challenges of working at home, struggles with online work and skill maintenance, and caring responsibilities; loss and vulnerability, including reduced social connections, lack of support, vulnerability, feelings of loss and grief, and concern for others; detrimental effects on health and wellbeing, including anxiety, low or unstable mood, poorer physical health, and lack of motivation; and professional and personal opportunities, including coping well or living more healthily, more time and less pressure, new possibilities and activities, enhanced social connections, and new skills. Lockdown 1.0 had profound effects on performing arts professionals, but our findings reveal some opportunities and compelling links between positive wellbeing and physical activity.