Cardiovascular and Noncardiovascular Prescribing and Mortality After Takotsubo Comparison With Myocardial Infarction and General Population.

Background: Takotsubo syndrome is an increasingly common cardiac emergency with no known evidence-based treatment. Objectives: The purpose of this study was to investigate cardiovascular mortality and medication use after takotsubo syndrome. Methods: In a case-control study, all patients with takotsubo syndrome in Scotland between 2010 and 2017 (n = 620) were age, sex, and geographically matched to individuals in the general population (1:4, n = 2,480) and contemporaneous patients with acute myocardial infarction (1:1, n = 620). Electronic health record data linkage of mortality outcomes and drug prescribing were analyzed using Cox proportional hazard regression models. Results: Of the 3,720 study participants (mean age, 66 years; 91% women), 153 (25%) patients with takotsubo syndrome died over the median of 5.5 years follow-up. This exceeded mortality rates in the general population (N = 374 [15%]; HR: 1.78 [95% CI: 1.48-2.15], P < 0.0001), especially for cardiovascular (HR: 2.47 [95% CI: 1.81-3.39], P < 0.001) but also noncardiovascular (HR: 1.48 [95% CI: 1.16-1.87], P = 0.002) deaths. Mortality rates were lower for patients with takotsubo syndrome than those with myocardial infarction (31%, 195/620; HR: 0.76 [95% CI: 0.62-0.94], P = 0.012), which was attributable to lower rates of cardiovascular (HR: 0.61 [95% CI: 0.44-0.84], P = 0.002) but not non-cardiovascular (HR: 0.92 [95% CI: 0.69-1.23], P = 0.59) deaths. Despite comparable medications use, cardiovascular therapies were consistently associated with better survival in patients with myocardial infarction but not in those with takotsubo syndrome. Diuretic (P = 0.01), anti-inflammatory (P = 0.002), and psychotropic (P < 0.001) therapies were all associated with worse outcomes in patients with takotsubo syndrome. Conclusions: In patients with takotsubo syndrome, cardiovascular mortality is the leading cause of death, and this is not associated with cardiovascular therapy use.

Comparison of intramyocellular lipid metabolism in patients with diabetes and male athletes.

Despite opposing insulin sensitivity and cardiometabolic risk, both athletes and patients with type 2 diabetes have increased skeletal myocyte fat storage: the so-called "athlete's paradox". In a parallel non-randomised, non-blinded trial (NCT03065140), we characterised and compared the skeletal myocyte lipid signature of 29 male endurance athletes and 30 patients with diabetes after undergoing deconditioning or endurance training respectively. The primary outcomes were to assess intramyocellular lipid storage of the vastus lateralis in both cohorts and the secondary outcomes were to examine saturated and unsaturated intramyocellular lipid pool turnover. We show that athletes have higher intramyocellular fat saturation with very high palmitate kinetics, which is attenuated by deconditioning. In contrast, type 2 diabetes patients have higher unsaturated intramyocellular fat and blunted palmitate and linoleate kinetics but after endurance training, all were realigned with those of deconditioned athletes. Improved basal insulin sensitivity was further associated with better serum cholesterol/triglycerides, glycaemic control, physical performance, enhanced post insulin receptor pathway signalling and metabolic sensing. We conclude that insulin-resistant, maladapted intramyocellular lipid storage and turnover in patients with type 2 diabetes show reversibility after endurance training through increased contributions of the saturated intramyocellular fatty acid pools. Clinical Trial Registration: NCT03065140: Muscle Fat Compartments and Turnover as Determinant of Insulin Sensitivity (MISTY).

Impact of remoteness and rurality on the treatment and survival of patients with glioblastoma in the north of Scotland.

Background: The geographical catchment area served by the Neurosurgical Unit in Aberdeen, Scotland is the largest in the United Kingdom. We examined whether a distance-decay effect on survival exists for patients diagnosed with glioblastoma, who have to travel substantial distances for neurosurgical and oncological treatment in the north of Scotland. Methods: Electronic medical records of adult patients with glioblastoma, referred for treatment between 2007 and 2018, who underwent surgical resection were reviewed. Travel time by car (as a measure of distance travelled) was calculated from the patients' home to their general practice (GP) and to their main neuro-oncological centre. Results: There were 122 patients; 71 (58.2%) were male and the mean age was 57.8 years. The urban-rural split was 61.5% and 38.5%, respectively. Median driving time to the neuro-oncological centre was 36 min and to the GP this was 6 min. Most patients underwent either sub-total (49.6%) or gross total (46.3%) surgical resection. Post-operative treatments included: radiotherapy only (15.6%), chemotherapy only (6.6%), and chemotherapy with radiotherapy (63.1%). Temozolomide was used in 70.5% of patients. Seventeen patients did not receive any post-operative chemo-radiotherapy. The median survival time was 345 days. There was no statistically significant association between distance travelled and survival time in days. MGMT methylation status, extent of resection, Charlson co-morbidity index and treatment received significantly affected survival. Conclusions: There was no evidence of disadvantage on survival time for patients living further from their neuro-oncological centre compared to those who live nearer.

Epigenetic studies in children at risk of stunting and their parents in India, Indonesia and Senegal: a UKRI GCRF Action Against Stunting Hub protocol paper.

INTRODUCTION: In 2020, an estimated 150 million children under the age of 5 years were stunted. Stunting results from early-life adversity and it is associated with significant physical and cognitive deficit, lifelong socioeconomic disadvantage and reduced life expectancy. There is a need to understand the causes of stunting and its effects in order to develop strategies to avoid it and to mitigate the consequences once stunting has occurred. Epigenetics is an important mechanism through which early-life factors are thought to influence biological function, with long-term consequences. We describe a series of epigenetic studies designed to understand how early-life adversity results in stunting and to inform the development of practical tools such as predictive markers and therapeutic targets. This work is part of the UKRI GCRF Action Against Stunting Hub. METHODS AND ANALYSIS: The project-in India, Indonesia and Senegal-comprises an observational study of mothers, fathers, and offspring (n=500) spanning the first 1000 days of life, and an intervention study in each country. Epigenetic status (DNA methylation) is determined in saliva from babies collected within 1 month of birth and again at 18 months of age, and from mothers and fathers around the time of birth. Epigenome-wide analysis is carried out using the Illumina EPIC array, augmented by high-definition sequencing approaches. Statistical analysis is carried out at the level of candidate genes/regions, higher dimensional epigenetic states and epigenome-wide association. Data analysis focuses on the determinants of stunting, the effectiveness of interventions, population comparisons and the link between epigenetics and other thematic areas, which include anthropometry, microbiome, gut health, parasitology, cognition, nutrition, food hygiene and water sanitation, food systems and the home environment. ETHICS AND DISSEMINATION: This study has been approved by the relevant Ethics Committees in Indonesia, India and Senegal, and the UK. Research data will be published and posted in public repositories.

New supporting data to guide the use of evident toxicity in acute oral toxicity studies (OECD TG 420).

Currently there are three test guidelines (TG) for acute oral toxicity studies of substances or mixtures from the Organisation for Economic Co-operation and Development (OECD). TG 423 and TG 425 use lethality as an endpoint, while TG 420 replaces death with 'evident toxicity', defined as clear signs that exposure to a higher dose would result in death. However, the perceived subjectivity of 'evident toxicity' may be preventing wider use of TG 420. To address this, the UK National Centre for the Replacement, Refinement and Reduction of Animals in Research (NC3Rs) and the European Partnership for Alternative Approaches to Animal Testing (EPAA) collaborated to provide recommendations on the recognition of 'evident toxicity'. Historical data from acute oral toxicity studies were analysed for clinical signs at the lower dose that could have predicted death at the higher dose. Several signs including ataxia, laboured respiration, and eyes partially closed, alone or in combination, are highly predictive. Others such as lethargy, decreased respiration, and loose faeces have lower but still appreciable positive predictive value (PPV). The data has been used to develop recommendations to promote use of TG 420 and thus reduce the suffering and numbers of animals used in acute oral toxicity studies.

Comparing self-reported energy intake using an online dietary tool with energy expenditure by an activity tracker.

OBJECTIVE: The aim of this study was to compare self-reported total energy intake (TEI) collected using an online multiple-pass 24-h dietary recall tool (Intake24) with total energy expenditure (TEE) estimated from Fitbit Charge 2-improved algorithms in adults from the NoHoW trial (12-mo weight maintenance after free-living weight loss). METHODS: Bland-Altman plots were used to assess the level of agreement between TEI and TEE at baseline and after 12 mo. The ratio of TEI to TEE was also calculated. RESULTS: Data from 1323 participants (71% female) was included in the analysis (mean ± SD: age 45 ± 12 y, body mass index 29.7 ± 5.4 kg/m2, initial weight loss 11.5 ± 6.5 kg). The TEI was lower than TEE on average by 33%, with limits of agreement ranging from -91% to +25%. Men, younger individuals, those with higher body mass index, those with the greater weight loss before enrollment, and those who gained weight during the study underestimated to a greater extent. CONCLUSIONS: These findings contribute to the ongoing research examining the validity of technology-based dietary assessment tools.

Impaired Cardiac and Skeletal Muscle Energetics Following Anthracycline Therapy for Breast Cancer.

BACKGROUND: Anthracycline-related cardiac toxicity is a recognized consequence of cancer therapies. We assess resting cardiac and skeletal muscle energetics and myocyte, sarcomere, and mitochondrial integrity in patients with breast cancer receiving epirubicin. METHODS: In a prospective, mechanistic, observational, longitudinal study, we investigated chemotherapy-naive patients with breast cancer receiving epirubicin versus sex- and age-matched healthy controls. Resting energetic status of cardiac and skeletal muscle (phosphocreatine/gamma ATP and inorganic phosphate [Pi]/phosphocreatine, respectively) was assessed with 31P-magnetic resonance spectroscopy. Cardiac function and tissue characterization (magnetic resonance imaging and 2D-echocardiography), cardiac biomarkers (serum NT-pro-BNP and high-sensitivity troponin I), and structural assessments of skeletal muscle biopsies were obtained. All study assessments were performed before and after chemotherapy. RESULTS: Twenty-five female patients with breast cancer (median age, 53 years) received a mean epirubicin dose of 304 mg/m2, and 25 age/sex-matched controls were recruited. Despite comparable baseline cardiac and skeletal muscle energetics with the healthy controls, after chemotherapy, patients with breast cancer showed a reduction in cardiac phosphocreatine/gamma ATP ratio (2.0±0.7 versus 1.1±0.5; P=0.001) and an increase in skeletal muscle Pi/phosphocreatine ratio (0.1±0.1 versus 0.2±0.1; P=0.022). This occurred in the context of increases in left ventricular end-systolic and end-diastolic volumes (P=0.009 and P=0.008, respectively), T1 and T2 mapping (P=0.001 and P=0.028, respectively) but with preserved left ventricular ejection fraction, mass and global longitudinal strain, and no change in cardiac biomarkers. There was preservation of the mitochondrial copy number in skeletal muscle biopsies but a significant increase in areas of skeletal muscle degradation (P=0.001) in patients with breast cancer following chemotherapy. Patients with breast cancer demonstrated a reduction in skeletal muscle sarcomere number from the prechemotherapy stage compared with healthy controls (P=0.013). CONCLUSIONS: Contemporary doses of epirubicin for breast cancer treatment result in a significant reduction of cardiac and skeletal muscle high-energy 31P-metabolism alongside structural skeletal muscle changes. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT04467411.

Are motivational and self-regulation factors associated with 12 months' weight regain prevention in the NoHoW study? An analysis of European adults.

PURPOSE: Preventing weight regain can only be achieved by sustained changes in energy balance-related behaviors that are associated with weight, such as diet and physical activity. Changes in motivation and self-regulatory skills can support long-term behavioral changes in the context of weight loss maintenance. We propose that experiencing a supportive climate care is associated with enhanced satisfaction of basic psychological needs, intrinsic goals, and autonomous motivation. These factors are expected to be associate with the utilization of self-regulation skills, leading to more sustained behavior changes and ultimately preventing weight regain. This hypothesis was tested in this ancillary analysis of the NoHoW trial, where the study arms were pooled and followed for 12 months. METHODS: The NoHoW was a three-center, large-scale weight regain prevention full factorial trial. In this longitudinal study, data were collected in adults who lost > 5% weight in the past year (N = 870, complete data only, 68.7% female, 44.10 ± 11.86 years, 84.47 ± 17.03 kg) during their participation in a 12-month digital behavior change intervention. Weight and validated measures of motivational- and self-regulatory skills-related variables were collected at baseline, six- and 12 months. Change variables were used in Mplus' path analytical models informed by NoHoW's logic model. RESULTS: The bivariate correlations confirmed key mediators' potential effect on weight outcomes in the expected causal direction. The primary analysis showed that a quarter of the variance (r2 = 23.5%) of weight regain prevention was achieved via the mechanisms of action predicted in the logic model. Specifically, our results show that supportive climate care is associated with needs satisfaction and intrinsic goal content leading to better weight regain prevention via improvements in self-regulatory skills and exercise-controlled motivation. The secondary analysis showed that more mechanisms of action are significant in participants who regained or maintained their weight. CONCLUSIONS: These results contribute to a better understanding of the mechanisms of action leading to behavior change in weight regain prevention. The most successful participants used only a few intrinsic motivation-related mechanisms of action, suggesting that habits may have been learned. While developing a digital behavior change intervention, researchers and practitioners should consider creating supportive climate care to improve needs satisfaction and intrinsic goal contents. TRIAL REGISTRATION: ISRCTN, ISRCTN88405328 , registered 12/22/2016.

Consumption of foods with the highest nutritional quality, and the lowest greenhouse gas emissions and price, differs between socio-economic groups in the UK population.

OBJECTIVE: To establish a baseline understanding of whether consuming food with the highest nutritional quality, lowest greenhouse gas emissions (GHGE) and cost differs between different UK demographic and socio-economic population groups. DESIGN: Multiple linear regression models were fitted to evaluate the relationship between predictor socio-demographic variables in this study (i.e. sex, ethnic group, age, BMI and level of deprivation) and the response variables (i.e. consumption of items considered most nutritious, with a low GHGE and price, as a proportion of total items consumed). SETTING: The UK. PARTICIPANTS: 1374 adult (18-65 years) participants from the National Diet and Nutrition Survey latest waves 9-11 (2016-2017 and 2018-2019). RESULTS: Based on the total energy consumption in a day, the average diet-based GHGE was significantly higher for participants with a higher BMI. Non-white and most deprived participants spent significantly (P < 0·001) less money per total energy consumption. Participants with a BMI between 18·6 and 39·9 kg/m2 and those living in the least deprived areas consumed a significantly (P < 0·001) higher amount of those items considered the most nutritious, with the lowest GHGE and cost per 100 kcal. CONCLUSIONS: Consumption of food with the highest nutritional quality, lowest GHGE and cost in the UK varies among those with different socio-demographic characteristics, especially the deprivation level of participants. Our analysis endorses the consideration of environmental sustainability and affordability, in addition to the consideration of nutritional quality from a health perspective, to make current dietary guidelines more encompassing and equitable.

Diet composition and energy intake in humans.

Absolute energy from fats and carbohydrates and the proportion of carbohydrates in the food supply have increased over 50 years. Dietary energy density (ED) is primarily decreased by the water and increased by the fat content of foods. Protein, carbohydrates and fat exert different effects on satiety or energy intake (EI) in the order protein > carbohydrates > fat. When the ED of different foods is equalized the differences between fat and carbohydrates are modest. Covertly increasing dietary ED with fat, carbohydrate or mixed macronutrients elevates EI, producing weight gain and vice versa. In more naturalistic situations where learning cues are intact, there appears to be greater compensation for the different ED of foods. There is considerable individual variability in response. Macronutrient-specific negative feedback models of EI regulation have limited capacity to explain how availability of cheap, highly palatable, readily assimilated, energy-dense foods lead to obesity in modern environments. Neuropsychological constructs including food reward (liking, wanting and learning), reactive and reflective decision making, in the context of asymmetric energy balance regulation, give more comprehensive explanations of how environmental superabundance of foods containing mixtures of readily assimilated fats and carbohydrates and caloric beverages elevate EI through combined hedonic, affective, cognitive and physiological mechanisms. This article is part of a discussion meeting issue 'Causes of obesity: theories, conjectures and evidence (Part II)'.

Testing motivational and self-regulatory mechanisms of action on device-measured physical activity in the context of a weight loss maintenance digital intervention: A secondary analysis of the NoHoW trial.

BACKGROUND: To date, few digital behavior change interventions for weight loss maintenance focusing on long-term physical activity promotion have used a sound intervention design grounded on a logic model underpinned by behavior change theories. The current study is a secondary analysis of the weight loss maintenance NoHoW trial and investigated putative mediators of device-measured long-term physical activity levels (six to 12 months) in the context of a digital intervention. METHODS: A subsample of 766 participants (Age = 46.2 ± 11.4 years; 69.1% female; original NoHoW sample: 1627 participants) completed all questionnaires on motivational and self-regulatory variables and had all device-measured physical activity data available for zero, six and 12 months. We examined the direct and indirect effects of Virtual Care Climate on post intervention changes in moderate-to-vigorous physical activity and number of steps (six to 12 months) through changes in the theory-driven motivational and self-regulatory mechanisms of action during the intervention period (zero to six months), as conceptualized in the logic model. RESULTS: Model 1 tested the mediation processes on Steps and presented a poor fit to the data. Model 2 tested mediation processes on moderate-to-vigorous physical activity and presented poor fit to the data. Simplified models were also tested considering the autonomous motivation and the controlled motivation variables independently. These changes yielded good results and both models presented very good fit to the data for both outcome variables. Percentage of explained variance was negligible for all models. No direct or indirect effects were found from Virtual Care Climate to long term change in outcomes. Indirect effects occurred only between the sequential paths of the theory-driven mediators. CONCLUSION: This was one of the first attempts to test a serial mediation model considering psychological mechanisms of change and device-measured physical activity in a 12-month longitudinal trial. The model explained a small proportion of variance in post intervention changes in physical activity. We found different pathways of influence on theory-driven motivational and self-regulatory mechanisms but limited evidence that these constructs impacted on actual behavior change. New approaches to test these relationships are needed. Challenges and several alternatives are discussed. TRIAL REGISTRATION: ISRCTN Registry, ISRCTN88405328. Registered December 16, 2016, https://www.isrctn.com/ISRCTN88405328.

Exploratory analysis of reflective, reactive, and homeostatic eating behaviour traits on weight change during the 18-month NoHoW weight maintenance trial.

Behaviour change interventions for weight management have found varied effect sizes and frequent weight re-gain after weight loss. There is interest in exploring whether differences in eating behaviour can be used to develop tailored weight management programs. This secondary analysis of an 18-month weight maintenance randomised controlled trial (RCT) aimed to investigate the association between individual variability in weight maintenance success and change in eating behaviour traits (EBT). Data was analysed from the NoHoW trial (Scott et al., 2019), which was designed to measure processes of change after weight loss of ≥5% body weight in the previous year. The sample included 1627 participants (mean age = 44.0 years, SD = 11.9, mean body mass index (BMI) = 29.7 kg/m2, SD = 5.4, gender = 68.7% women/31.3% men). Measurements of weight (kg) and 7 EBTs belonging to domains of reflective, reactive, or homeostatic eating were taken at 4 time points up to 18-months. Increases in measures of 'reactive eating' (binge eating, p < .001), decreases in 'reflective eating' (restraint, p < .001) and changes in 'homeostatic eating' (unlimited permission to eat, p < .001 and reliance on hunger and satiety cues, p < .05) were significantly and independently associated with concomitant weight change. Differences in EBT change were observed between participants who lost, maintained, or re-gained weight for all EBTs (p < .001) except for one subscale of intuitive eating (eating for physical reasons, p = .715). Participants who lost weight (n = 322) exhibited lower levels of reactive eating and higher levels of reflective eating than participants who re-gained weight (n = 668). EBT domains can identify individuals who need greater support to progress in weight management interventions. Increasing reflective eating and reducing reactive eating may enhance weight management success.

A grape seed and bilberry extract reduces blood pressure in individuals at risk of developing type 2 diabetes: the PRECISE study, a double-blind placebo-controlled cross-over intervention study.

Background: Type 2 Diabetes Mellitus (T2DM) is a major risk factor for the development of cardiometabolic diseases. T2DM prevention is largely based on weight-loss and whole diet changes, but intervention with dietary plant bioactives may also improve metabolic health. Objective: To assess whether supplementation with bilberry and grape seed extract for 12 weeks improves cardiometabolic outcomes in individuals at risk of developing T2DM, and to determine whether individual treatment response is associated with differences in gut microbiota composition and levels of phenolic metabolites in blood and feces. Methods: In the randomized, double-blind, placebo-controlled, cross-over PRECISE intervention study, 14 participants, aged ≥45 years, with a BMI >28 kg/m2, and having an increased risk of T2DM, received a supplement containing 250 mg of bilberry plus 300 mg of grape seed extract, or 550 mg of a control extract, per day, for 12 weeks each. Blood samples were obtained for the assessment of HbA1c, fasting glucose, oral glucose tolerance tests, insulin, glucagon levels, total, LDL and HDL cholesterol, and phenolic acids. We also assessed advanced glycation end products in the skin, ambulatory 24 hours blood pressure, 7-day dietary intake by weighed food diaries, fecal levels of phenolic metabolites using LC-MS/MS and gut microbiota composition using 16S rRNA gene sequencing analysis. Results: The combined bilberry and grape seed extract did not affect glucose and cholesterol outcomes, but it decreased systolic and diastolic ambulatory blood pressure by 4.7 (p < 0.001) and 2.3 (p = 0.0009) mmHg, respectively. Eight out of fourteen participants were identified as blood pressure 'responders'. These responders had higher levels of phenylpropionic and phenyllactic acids in their fecal samples, and a higher proportional abundance of Fusicatenibacter-related bacteria (p < 0.01) in their baseline stool samples. Conclusion: Long-term supplementation with bilberry and grape seed extract can improve systolic and diastolic blood pressure in individuals at risk of T2DM. Individual responsiveness was correlated with the presence of certain fecal bacterial strains, and an ability to metabolize (epi)catechin into smaller phenolic metabolites.Clinical trial registry number: Research Registry (number 4084).

Ultrafiltration versus Diuretics on Prognostic Cardiac and Renal Biomarkers in Acute Decompensated Heart Failure: A Systematic Review and Meta-Analysis.

Existing systematic reviews have insufficiently delineated the differing cardiac and renal profile of ultrafiltration compared to diuretics as a method of decongestion in acute decompensated heart failure. This meta-analysis will investigate the impact of ultrafiltration compared to diuretics on prognostic cardiac and renal biomarkers. We searched PubMed Central, Ovid MEDLINE®, Ovid Embase, all EBM reviews, and Web of Science Core Collection for randomised controlled trials published before 21 July 2022. Our main outcome measures were cardiac (brain natriuretic peptide and N-terminal pro-brain natriuretic peptide) and renal biomarkers (serum creatinine, serum sodium, and blood urea nitrogen). A total of 10 randomised trials were included in our analysis after screening. An inverse-variance random effects meta-analysis of the pooled results demonstrated no significant difference between ultrafiltration and diuretics for brain natriuretic peptide, N-terminal pro-brain natriuretic peptide, creatinine, sodium and long-term blood urea nitrogen. However, ultrafiltration produced statistically greater increases in blood urea nitrogen in the short-term (mean difference, 3.88; 95% confidence interval 0.59-7.17 mg/dL). Overall, ultrafiltration produces a similar impact on prognostic cardiac and renal biomarkers when compared to diuretic therapy. We highlight ultrafiltration's significant impact on short-term BUN and recommend further research to investigate more optimal protocols of ultrafiltration administration.

Beyond purified dietary fibre supplements: Compositional variation between cell wall fibre from different plants influences human faecal microbiota activity and growth in vitro.

Dietary fibre is a major energy source for the human gut microbiota, but it is unclear to what extent the fibre source and complexity affect microbial growth and metabolite production. Cell wall material and pectin were extracted from five different dicotyledon plant sources, apples, beet leaves, beetroots, carrots and kale, and compositional analysis revealed differences in the monosaccharide composition. Human faecal batch incubations were conducted with 14 different substrates, including the plant extracts, wheat bran and commercially available carbohydrates. Microbial activity was determined for up to 72 h by measuring gas and fermentation acid production, total bacteria (by qPCR) and microbial community composition by 16S rRNA amplicon sequencing. The more complex substrates gave rise to more microbiota variation compared with the pectins. The comparison of different plant organs showed that the leaves (beet leaf and kale) and roots (carrot and beetroot) did not give rise to similar bacterial communities. Rather, the compositional features of the plants, such as high arabinan levels in beet and high galactan levels in carrot, appear to be major predictors of bacterial enrichment on the substrates. Thus, in-depth knowledge on dietary fibre composition should aid the design of diets focused on optimizing the microbiota.

Habitual consumption of high-fibre bread fortified with bean hulls increased plasma indole-3-propionic concentration and decreased putrescine and deoxycholic acid faecal concentrations in healthy volunteers.

Only 6 to 8 % of the UK adults meet the daily recommendation for dietary fibre. Fava bean processing lead to vast amounts of high-fibre by-products such as hulls. Bean hull fortified bread was formulated to increase and diversify dietary fibre while reducing waste. This study assessed the bean hull: suitability as a source of dietary fibre; the systemic and microbial metabolism of its components and postprandial events following bean hull bread rolls. Nine healthy participants (53·9 ± 16·7 years) were recruited for a randomised controlled crossover study attending two 3 days intervention sessions, involving the consumption of two bread rolls per day (control or bean hull rolls). Blood and faecal samples were collected before and after each session and analysed for systemic and microbial metabolites of bread roll components using targeted LC-MS/MS and GC analysis. Satiety, gut hormones, glucose, insulin and gastric emptying biomarkers were also measured. Two bean hull rolls provided over 85 % of the daily recommendation for dietary fibre; but despite being a rich source of plant metabolites (P = 0·04 v. control bread), these had poor systemic bioavailability. Consumption of bean hull rolls for 3 days significantly increased plasma concentration of indole-3-propionic acid (P = 0·009) and decreased faecal concentration of putrescine (P = 0·035) and deoxycholic acid (P = 0·046). However, it had no effect on postprandial plasma gut hormones, bacterial composition and faecal short chain fatty acids amount. Therefore, bean hulls require further processing to improve their bioactives systemic availability and fibre fermentation.

Structural and Functional Brain Changes in Acute Takotsubo Syndrome.

BACKGROUND: Takotsubo syndrome mimics an acute myocardial infarction, typically in the aftermath of mental or physical stress. OBJECTIVES: The mechanism by which emotional processing in the context of stress leads to significant cardiac injury is poorly understood, so a full exploration of brain structure and function in takotsubo syndrome patients merits investigation. METHODS: Twenty-five acute (<5 days) takotsubo patients and 25 control subjects were recruited into this observational cross-sectional study. Surface-based morphometry was carried out on magnetic resonance imaging (MRI) brain scans to extract cortical morphology based on volume, thickness, and surface area with the use of Freesurfer. Cortical morphology general linear models were corrected for age, sex, photoperiod, and total brain volume. Resting-state functional MRI and diffusion tensor tractography images were preprocessed and analyzed with the use of the Functional Magnetic Resonance Imaging of the Brain Diffusion Toolbox and Functional Connectivity Toolbox. RESULTS: There was significantly smaller total white matter and subcortical gray matter volumes in takotsubo (P < 0.001), with smaller total brain surface area but increased total cortical thickness (both P < 0.001). Individual gray matter regions (hippocampus and others) were significantly smaller in takotsubo (P < 0.001); only thalamus and insula were larger (P < 0.001). There was significant hyperfunctional and hypofunctional connectivity in multiple areas, including thalamus-amygdala-insula and basal ganglia (P < 0.05). All structural tractography connections were increased in takotsubo (P < 0.05). CONCLUSIONS: The authors showed smaller gray and white matter volumes driven by smaller cortical surface area, but increased cortical thickness and structural tractography connections with bidirectional changes in functional connectivity linked to emotion, language, reasoning, perception, and autonomic control. These are interventional targets in takotsubo patients' rehabilitation.

Substituting sedentary time with sleep or physical activity and subsequent weight-loss maintenance.

OBJECTIVE: In this study, the associations between the substitution of sedentary time with sleep or physical activity at different intensities and subsequent weight-loss maintenance were examined. METHODS: This prospective study included 1152 adults from the NoHoW trial who had achieved a successful weight loss of ≥5% during the 12 months prior to baseline and had BMI ≥25 kg/m2 before losing weight. Physical activity and sleep were objectively measured during a 14-day period at baseline. Change in body weight was included as the primary outcome. Secondary outcomes were changes in body fat percentage and waist circumference. Cardiometabolic variables were included as exploratory outcomes. RESULTS: Using isotemporal substitution models, no associations were found between activity substitutions and changes in body weight or waist circumference. However, the substitution of sedentary behavior with moderate-to-vigorous physical activity was associated with a decrease in body fat percentage during the first 6 months of the trial (-0.33% per 30 minutes higher moderate-to-vigorous physical activity [95% CI: -0.60% to -0.07%], p = 0.013). CONCLUSIONS: Sedentary behavior had little or no influence on subsequent weight-loss maintenance, but during the early stages of a weight-loss maintenance program, substituting sedentary behavior with moderate-to-vigorous physical activity may prevent a gain in body fat percentage.

Motivational and self-efficacy reciprocal effects during a 12-month' weight regain prevention program.

OBJECTIVE: Weight regain prevention is a critical public health challenge. Digital behaviour change interventions provide a scalable platform for applying and testing behaviour change theories in this challenging context. This study's goal was to analyse reciprocal effects between psychosocial variables (i.e., needs satisfaction, eating regulation, self-efficacy) and weight over 12 months using data from a large sample of participants engaged in a weight regain prevention trial. METHODS: The NoHoW study is a three-centre, large-scale weight regain prevention trial. Adults who lost >5% of their weight in the past year (N = 1627, 68.7% female, 44.10 ± 11.86 years, 84.47 ± 17.03 kg) participated in a 12-month' digital behaviour change-based intervention. Weight and validated measures of basic psychological needs satisfaction, eating regulation and self-efficacy were collected at baseline, six- and 12 months. Correlational, latent growth models and cross-lagged analysis were used to identify potential reciprocal effects. RESULTS: Baseline higher scores of needs satisfaction and self-efficacy were associated with six- and 12-month' weight loss. Baseline weight was linked to all psychosocial variables at six months, and six-months weight was associated with needs satisfaction and self-efficacy at 12 months. During the 12 months, increases in eating regulation, needs satisfaction and self-efficacy were associated with weight loss over the same period, and reciprocal effects were observed between the variables, suggesting the existence of Weight Management Cycles. CONCLUSIONS: While further studies are needed, during long-term weight regain prevention, weight decrease, needs satisfaction and self-efficacy may lead to Weight Management Cycles, which, if recurrent, may provide sustained prevention of weight regain.