Cross-sectional associations between dietary antioxidant vitamins C, E and carotenoid intakes and sarcopenic indices in women aged 18–79 years

The prevalence of sarcopenia is increasing in aging populations, so prevention is critical. Vitamins (A, C, E and carotenoids) modify skeletal muscle via protein and collagen synthesis and anti-inflammatory activities. Previous studies have not investigated intake of these vitamins in relation to sarcopenic indices in both younger and older-aged women. Indices of skeletal muscle mass (as fat-free mass (FFM) relative to body size) were measured using DXA and leg explosive power (LEP) using the Nottingham Power Rig in 2570 women aged 18-79 years. Adjusted measures of skeletal muscle were calculated according to quintiles of vitamin C, E, retinol and carotenoid intake, derived from Food Frequency Questionnaires, after stratification by age. Higher vitamin C intake was associated with significantly higher indices of FFM and LEP, (Q5-Q1 = 2.0-12.8%, P < 0.01-0.02). Intakes of total and individual carotenoids were significantly associated with indices of FFM and LEP (Q5-Q1 = 1.0-7.5%). Vitamin E was significantly associated with FFM% and FFM BMI only. In mutually adjusted analysis with vitamin C, total carotene, vitamin E and protein in the model, the strongest associations were with vitamin C. These associations were stronger in younger women (< 65 years). For the first time, our research shows higher dietary intakes of antioxidant vitamins, particularly vitamin C, is associated with higher skeletal muscle mass and power in free-living women. These findings have relevance for the treatment and prevention of frailty and sarcopenia throughout adulthood

The relationship between weight-related indicators and depressive symptoms during adolescence and adulthood: results from two twin studies

Background: The association between weight and depressive symptoms is well established, but the direction of effects remains unclear. Most studies rely on body mass index (BMI) as the sole weight indicator, with few examining the aetiology of the association between weight indicators and depressive symptoms. // Methods: We analysed data from the Twins Early Development Study (TEDS) and UK Adult Twin Registry (TwinsUK) (7658 and 2775 twin pairs, respectively). A phenotypic cross-lagged panel model assessed the directionality between BMI and depressive symptoms at ages 12, 16, and 21 years in TEDS. Bivariate correlations tested the phenotypic association between a range of weight indicators and depressive symptoms in TwinsUK. In both samples, structural equation modelling of twin data investigated genetic and environmental influences between weight indicators and depression. Sensitivity analyses included two-wave phenotypic cross-lagged panel models and the exclusion of those with a BMI <18.5. // Results: Within TEDS, the relationship between BMI and depression was bidirectional between ages 12 and 16 with a stronger influence of earlier BMI on later depression. The associations were unidirectional thereafter with depression at 16 influencing BMI at 21. Small genetic correlations were found between BMI and depression at ages 16 and 21, but not at 12. Within TwinsUK, depression was weakly correlated with weight indicators; therefore, it was not possible to generate precise estimates of genetic or environmental correlations. // Conclusions: The directionality of the relationship between BMI and depression appears to be developmentally sensitive. Further research with larger genetically informative samples is needed to estimate the aetiological influence on these associations

Effect of gut microbiome modulation on muscle function and cognition:the PROMOTe randomised controlled trial

Studies suggest that inducing gut microbiota changes may alter both musclephysiology and cognitive behaviour. Gut microbiota may play a role in bothanabolic resistance of older muscle, and cognition. In this placebo controlleddouble blinded randomised controlled trial of 36 twin pairs (72 individuals),aged ≥60, each twin pair are block randomised to receive either placebo orprebiotic daily for 12 weeks. Resistance exercise and branched chain aminoacid (BCAA) supplementation is prescribed to all participants. Outcomes arephysical function and cognition. The trial is carried out remotely using videovisits, online questionnaires and cognitive testing, and posting of equipmentand biological samples. The prebiotic supplement is well tolerated and resultsin a changed gut microbiome [e.g., increased relative Bifidobacterium abundance].There is no significant difference between prebiotic and placebo forthe primary outcome of chair rise time (β=0.579; 95% CI −1.080-2.239p = 0.494). The prebiotic improves cognition (factor score versus placebo(β = −0.482; 95% CI,−0.813, −0.141; p = 0.014)). Our results demonstrate thatcheap and readily available gut microbiome interventions may improve cognitionin our ageing population. We illustrate the feasibility of remotelydelivered trials for older people, which could reduce under-representation ofolder people in clinical trials. ClinicalTrials.gov registration: NCT04309292

Detection of stable community structures within gut microbiota co-occurrence networks from different human populations

Microbes in the gut microbiome form sub-communities based on shared niche specialisations and specific interactions between individual taxa. The inter-microbial relationships that define these communities can be inferred from the co-occurrence of taxa across multiple samples. Here, we present an approach to identify comparable communities within different gut microbiota co-occurrence networks, and demonstrate its use by comparing the gut microbiota community structures of three geographically diverse populations. We combine gut microbiota profiles from 2,764 British, 1,023 Dutch, and 639 Israeli individuals, derive co-occurrence networks between their operational taxonomic units, and detect comparable communities within them. Comparing populations we find that community structure is significantly more similar between datasets than expected by chance. Mapping communities across the datasets, we also show that communities can have similar associations to host phenotypes in different populations. This study shows that the community structure within the gut microbiota is stable across populations, and describes a novel approach that facilitates comparative community-centric microbiome analyses

Low thrust propulsion in a coplanar circular restricted four body problem

This paper formulates a circular restricted four body problem (CRFBP), where the three primaries are set in the stable Lagrangian equilateral triangle configuration and the fourth body is massless. The analysis of this autonomous coplanar CRFBP is undertaken, which identies eight natural equilibria; four of which are close to the smaller body, two stable and two unstable, when considering the primaries to be the Sun and two smaller bodies of the solar system. Following this, the model incorporates `near term' low-thrust propulsion capabilities to generate surfaces of articial equilibrium points close to the smaller primary, both in and out of the plane containing the celestial bodies. A stability analysis of these points is carried out and a stable subset of them is identied. Throughout the analysis the Sun-Jupiter-Asteroid-Spacecraft system is used, for conceivable masses of a hypothetical asteroid set at the libration point L4. It is shown that eight bounded orbits exist, which can be maintained with a constant thrust less than 1:5 10&#x100000;4N for a 1000kg spacecraft. This illustrates that, by exploiting low-thrust technologies, it would be possible to maintain an observation point more than 66% closer to the asteroid than that of a stable natural equilibrium point. The analysis then focusses on a major Jupiter Trojan: the 624-Hektor asteroid. The thrust required to enable close asteroid observation is determined in the simplied CRFBP model. Finally, a numerical simulation of the real Sun-Jupiter-624 Hektor-Spacecraft is undertaken, which tests the validity of the stability analysis of the simplied model

Robust, reproducible clinical patterns in hospitalised patients with COVID-19

Background: Severe COVID-19 is characterised by fever, cough, and dyspnoea. Symptoms affecting other organ systems have been reported. However, it is the clinical associations of different patterns of symptoms which influence diagnostic and therapeutic decision-making. In this study, we applied simple machine learning techniques to a large prospective cohort of hospitalised patients with COVID-19 identify clinically meaningful sub-groups. Methods: We obtained structured clinical data on 59 011 patients in the UK (the ISARIC Coronavirus Clinical Characterisation Consortium, 4C) and used a principled, unsupervised clustering approach to partition the first 25 477 cases according to symptoms reported at recruitment. We validated our findings in a second group of 33 534 cases recruited to ISARIC-4C, and in 4 445 cases recruited to a separate study of community cases. Findings: Unsupervised clustering identified distinct sub-groups. First, a core symptom set of fever, cough, and dyspnoea, which co-occurred with additional symptoms in three further patterns: fatigue and confusion, diarrhoea and vomiting, or productive cough. Presentations with a single reported symptom of dyspnoea or confusion were common, and a subgroup of patients reported few or no symptoms. Patients presenting with gastrointestinal symptoms were more commonly female, had a longer duration of symptoms before presentation, and had lower 30-day mortality. Patients presenting with confusion, with or without core symptoms, were older and had a higher unadjusted mortality. Symptom clusters were highly consistent in replication analysis using a further 35446 individuals subsequently recruited to ISARIC-4C. Similar patterns were externally verified in 4445 patients from a study of self-reported symptoms of mild disease. Interpretation: The large scale of the ISARIC-4C study enabled robust, granular discovery and replication of patient clusters. Clinical interpretation is necessary to determine which of these observations have practical utility. We propose that four patterns are usefully distinct from the core symptom groups: gastro-intestinal disease, productive cough, confusion, and pauci-symptomatic presentations. Importantly, each is associated with an in-hospital mortality which differs from that of patients with core symptoms. These observations deepen our understanding of COVID-19 and will influence clinical diagnosis, risk prediction, and future mechanistic and clinical studies. Funding: Medical Research Council; National Institute Health Research; Well-come Trust; Department for International Development; Bill and Melinda Gates Foundation; Liverpool Experimental Cancer Medicine Centre

An Investigation Into Physical Frailty as a Link Between the Gut Microbiome and Cognitive Health

The preservation of cognitive abilities with aging is a priority both for individuals and nations given the aging populations of many countries. Recently the gut microbiome has been identified as a new territory to explore in relation to cognition. Experiments using rodents have identified a link between the gut microbiome and cognitive function, particularly that low microbial diversity leads to poor cognition function. Similar studies in humans could identify novel targets to encourage healthy cognition in an aging population. Here, we investigate the association of gut microbiota and cognitive function in a human cohort considering the influence of physical frailty. We analyzed 16S rRNA gene sequence data, derived from fecal samples obtained from 1,551 individuals over the age of 40. Cognitive data was collected using four cognitive tests: verbal fluency (n = 1,368), Deary-Liewald Reaction Time Test (DLRT; n = 873), Mini Mental State Examination (recall; n = 1,374) and Paired Associates Learning from the Cambridge Neuropsychological Test Automated Battery (CANTAB-PAL; n = 405). We use mixed effects models to identify associations with alpha diversity, operational taxonomic units (OTUs) and taxa and performed further analyses adjusting for physical frailty. We then repeated the analyses in a subset of individuals with dietary data, also excluding those using medications shown to influence gut microbiome composition. DLRT and verbal fluency were negatively associated with alpha diversity of the gut microbiota (False-Discovery Rate, FDR, p &lt; 0.05). However, when considering frailty as a covariate, only associations between the DLRT and diversity measures remained. Repeating analyses excluding Proton pump inhibitor (PPI) and antibiotic users and accounting for diet, we similarly observe significant negative associations between the DLRT and alpha diversity measures and a further negative association between DLRT and the abundance of the order Burkholderiales that remains significant after adjusting for host frailty. This highlights the importance of considering concurrent differences in physical health in studies of cognitive performance and suggests that physical health has a relatively larger association with the gut microbiome. However, the frailty independent cognitive-gut microbiota associations that were observed might represent important targets for further research, with potential for use in diagnostic surveillance in cognitive aging and interventions to improve vitality

Integrating Comprehensive Geriatric Assessment for people with COPD and frailty starting pulmonary rehabilitation: the Breathe Plus feasibility trial protocol.

One in five people with COPD also lives with frailty. People living with both COPD and frailty are at increased risk of poorer health and outcomes, and face challenges to completing pulmonary rehabilitation. Integrated approaches that are adapted to the additional context of frailty are required. The aim of the present study is to determine the feasibility of conducting a randomised controlled trial of an integrated Comprehensive Geriatric Assessment for people with COPD and frailty starting pulmonary rehabilitation. This is a multicentre, mixed-methods, assessor-blinded, randomised, parallel group, controlled feasibility trial ("Breathe Plus"; ISRCTN13051922). We aim to recruit 60 people aged ≥50 with both COPD and frailty referred for pulmonary rehabilitation. Participants will be randomised 1:1 to receive usual pulmonary rehabilitation, or pulmonary rehabilitation with an additional Comprehensive Geriatric Assessment. Outcomes (physical, psycho-social and service use) will be measured at baseline, 90 days and 180 days. We will also collect service and trial process data, and conduct qualitative interviews with a sub-group of participants and staff. We will undertake descriptive analysis of quantitative feasibility outcomes (recruitment, retention, missing data, blinding, contamination, fidelity), and framework analysis of qualitative feasibility outcomes (intervention acceptability and theory, outcome acceptability). Recommendations on progression to a full trial will comprise integration of quantitative and qualitative data, with input from relevant stakeholders. This study has been approved by a UK Research Ethics Committee (ref.: 19/LO/1402). This protocol describes the first study testing the feasibility of integrating a Comprehensive Geriatric Assessment alongside pulmonary rehabilitation, and testing this intervention within a mixed-methods randomised controlled trial

Higher dietary protein intake is associated with sarcopenia in older British twins

BACKGROUND: Sarcopenia, characterised by an accelerated loss of skeletal muscle mass and function, is associated with negative outcomes. This study aimed to evaluate factors associated with skeletal muscle strength, mass and sarcopenia, particularly protein intake, and to assess whether shared twin characteristics are important. METHODS: This study utilised cross-sectional data from a study of community-dwelling twins aged ≥60 years. Multivariable logistic regression and between- and within-twin pair regression modelling were used. RESULTS: Participants (n = 3,302) were 89% female (n = 2,923), aged a mean of 72.1 (±7.3) years and composed of 858 (55%) monozygotic, 709 (45%) dizygotic twin pairs and 168 individual lone twins. Using optimal protein intake as the reference group (1.0-1.3 g/kg/day), there was no significant association between protein intake (neither high nor low) and low muscle strength, or between low protein intake and sarcopenia (odds ratio (OR) 0.7; 95% confidence interval (CI) 0.39-1.25; P = 0.229) in unadjusted models. High protein intake (>1.3 g/kg/day) was associated with low muscle mass (OR 1.76; 95% CI 1.39-2.24; P < 0.0001), while low protein intake was protective (OR 0.52; 95% CI 0.40-0.67; P < 0.0001). High protein intake was associated with sarcopenia (OR 2.04; 95% CI 1.21-3.44; P = 0.008), and this was robust to adjustment for demographic, anthropometric and dietary factors. The association between muscle strength and weight, body mass index, healthy eating index, protein intake and alpha diversity was not significantly influenced by shared twin factors, indicating greater amenability to interventions. CONCLUSIONS: High protein intake is associated with sarcopenia in a cohort of healthy older twins

SARS-CoV-2 (COVID-19) infection in pregnant women: characterization of symptoms and syndromes predictive of disease and severity through real-time, remote participatory epidemiology

Objective: To test whether pregnant and non-pregnant women differ in COVID-19 symptom profile and severity. To extend previous investigations on hospitalized pregnant women to those who did not require hospitalization. Design: Observational study prospectively collecting longitudinal (smartphone application interface) and cross-sectional (web-based survey) data. Setting:Community-based self-participatory citizen surveillance in the United Kingdom, Sweden and the United States of America. Population: Two female community-based cohorts aged 18-44 years. The discovery cohort was drawn from 1,170,315 UK, Sweden and USA women (79 pregnant tested positive) who self-reported status and symptoms longitudinally via smartphone. The replication cohort included 1,344,966 USA women (134 pregnant tested positive) who provided cross-sectional self-reports. Methods: Pregnant and non-pregnant were compared for frequencies of symptoms and events, including SARS-CoV-2 testing and hospitalization rates. Multivariable regression was used to investigate symptoms severity and comorbidity effects. Results: Pregnant and non-pregnant women positive for SARS-CoV-2 infection were not different in syndromic severity. Pregnant were more likely to have received testing than non-pregnant, despite reporting fewer symptoms. Pre-existing lung disease was most closely associated with the syndromic severity in pregnant hospitalized women. Heart and kidney diseases and diabetes increased risk. The most frequent symptoms among all non-hospitalized women were anosmia [63% pregnant, 92% non-pregnant] and headache [72%, 62%]. Cardiopulmonary symptoms, including persistent cough [80%] and chest pain [73%], were more frequent among pregnant women who were hospitalized. Conclusions: Symptom characteristics and severity were comparable among pregnant and non-pregnant women, except for gastrointestinal symptoms. Consistent with observations in non-pregnant populations, lung disease and diabetes were associated with increased risk of more severe SARS-CoV-2 infection during pregnancy. Tweetable abstract: Pregnancy with SARS-CoV-2 has no higher risk of severe symptoms. Underlying lung disease or cardiac condition can increase risk. Competing Interest Statement: ATC previously served as an investigator on a clinical trial of diet and lifestyle using a separate mobile application that was supported by Zoe Global Ltd. Clinical Trial -- Funding Statement: This work was supported by Zoe Global. The Department of Twin Research receives grants from the Wellcome Trust (212904/Z/18/Z) and Medical Research Council/British Heart Foundation Ancestry and Biological Informative Markers for Stratification of Hypertension (AIMHY; MR/M016560/1), and support from the European Union, the Chronic Disease Research Foundation, Zoe Global, the NIHR Clinical Research Facility and the Biomedical Research Centre (based at Guys and St Thomas NHS Foundation Trust in partnership with Kings College London). The School of Biomedical Engineering & Imaging Science and Center for Medical Engineering at Kings College London receive grants from the Wellcome/EPSRC Centre for Medical Engineering [WT 203148/Z/16/Z]. E.M. is funded by the Skills Development Scheme of the Medical Research Council UK. C.M.A. is funded by NIDDK K23 DK120899 and the Boston Childrens Hospital Office of Faculty Development Career Development Award. CHS is supported by an Alzheimers Society Junior fellowship (AS-JF-17-011). W.M., J.S.B. and A.T.C. are supported by the Massachusetts Consortium on Pathogen Readiness (MassCPR) and Mark and Lisa Schwartz