Short chain fatty acid production from mycoprotein and mycoprotein fibre in an in vitro fermentation model

Dietary mycoprotein (marketed as QuornTM) has many health benefits, including reductions in energy intake. The majority of studies evaluating mycoprotein focus on the protein content and very few consider the fibre content. Fibre consumption is also associated with decreased energy intake, which is partly attributed to short chain fatty acids (SCFAs) from fibre fermentation by colonic bacteria. To study the SCFA-producing capability of mycoprotein, in vitro batch fermentations were conducted, and SCFA production compared with that from extracted mycoprotein fibre, oligofructose (OF), rhamnose, and laminarin. Mycoprotein and mycoprotein fibre were both fermentable, resulting in a total SCFA production of 24.9 (1.7) and 61.2 (15.7) mmol/L, respectively. OF led to a significantly higher proportion of acetate compared to all other substrates tested (92.6 (2.8)%, p < 0.01). Rhamnose generated the highest proportion of propionate (45.3 (2.0)%, p < 0.01), although mycoprotein and mycoprotein fibre yielded a higher proportion of propionate compared with OF and laminarin. Butyrate proportion was the highest with laminarin (28.0 (10.0)although mycoprotein fibre led to a significantly higher proportion than OF (p < 0.01). Mycoprotein is a valuable source of dietary protein, but its fibre content is also of interest. Further evaluation of the potential roles of the fibre content of mycoprotein is required

Exploration is dependent on reproductive state, not social state, in a cooperatively breeding bird

Personality is an intriguing phenomenon in populations because it constrains behavioral flexibility. One theory suggests that personality could be generated and maintained if dependent on asset protection. It is predicted that trade-offs with fitness expectations and survival probability encourage consistent behavioral differences among individuals (personality). Although not mutually exclusive, the social niche specialization hypothesis suggests that a group of individuals that repeatedly interact will develop personality to avoid costly social conflict. The point at which behavioral consistency originates in the social niche hypothesis is still unclear, with predictions for development after a change in social status. In the facultative cooperatively breeding Seychelles warbler (Acrocephalus sechellensis), residing on Cousin Island, breeding vacancies are limited and this forces individuals into different social roles. We used this system to test whether reproductive and social state predicted among-individual differences in exploration. We had 2 predictions. First, that an individual’s start in life can predict personality, whereby young individuals with a good start to life (associated with early age reproduction and earlier onset survival senescence) are fast explorers, suggesting reproductive state-dependence. Second, that an individual’s social status can predict personality, whereby dominant individuals will be fast explorers, suggesting that the behavior is social state-dependent. Neither of the behaviors was associated with social state and social state did not affect behavioral consistency. However, novel object exploration was associated with a proxy of reproductive state. Our results provide further support for state being a mechanism for generating individual differences in behavior

Quality of relationships as predictors of outcomes in people with dementia: a systematic review protocol

INTRODUCTION: Serious adverse outcomes for people with dementia include institutionalisation, hospitalisation, death, development of behavioural and psychiatric symptoms, and reduced quality of life. The quality of the relationship between the person with dementia and their informal/family carer is thought to affect the risk of these outcomes. However, little is known about which aspects of relationship quality are important, or how they affect outcomes for people with dementia. METHODS AND ANALYSIS: This will be a systematic review of the literature. Electronic databases MEDLINE, EMBASE, Web of Science, PsycInfo, the Cochrane Database, ALOIS and OpenGrey will be searched from inception. 2 independent reviewers will screen results for eligibility with standardised criteria. Data will be extracted for relevant studies, and information on the associations between relationship quality and dementia outcomes will be synthesised. Meta-analysis will be performed if possible to calculate pooled effect sizes. Narrative synthesis will be performed if study heterogeneity rules out meta-analysis. ETHICS AND DISSEMINATION: Ethical review is not necessary as this review summarises data from previous studies. Results will be disseminated via peer-reviewed publication. Results will also be disseminated to a patient and public involvement group and an expert panel for their views on the findings and implications for future work. TRIAL REGISTRATION NUMBER: CRD42015020518

The metformin in tuberous sclerosis (MiTS) study:A randomised double-blind placebo-controlled trial

Background: Tuberous Sclerosis Complex (TSC) is a genetic disorder characterised by the development of benign tumours secondary to loss of inhibitory regulation of the mTOR (mechanistic Target of Rapamycin) intracellular growth pathway. Metformin inhibits the mTOR pathway. We investigated whether metformin would reduce growth of hamartomas associated with tuberous sclerosis complex. / Methods: In this multicentre randomized, double-blind, placebo-controlled trial, patients with a clinical diagnosis of tuberous sclerosis, aged over 10 years and with at least one renal angiomyolipoma of greater than 1 cm in diameter were enrolled. Participants were randomly allocated (1:1) by a secure website to receive metformin or placebo for 12 months. The primary outcome was percentage volume change of renal angiomyolipomas (AML) at 12 months compared to baseline. Secondary outcomes were percentage change at 12 months from baseline in volume of cerebral Subependymal Giant Cell Astrocytomas (SEGA); appearance of facial and ungual hamartomas; frequency of epileptic seizures; and adaptive behaviour. The trial is registered with The International Standard Randomised Controlled Trial Number (ISRCTN), number 92545532, and the European Union Drug Regulating Authorities Clinical Trials (EUDRACT), number 2011-001319-30. / Findings: Between 1 November 2012 and 30 September 2015 72 patients were screened and 55 were randomly assigned to metformin (28) or placebo (27). Four participants withdrew between randomisation and starting treatment. All 51 patients who started therapy completed the trial and were assessed for outcome at 12 months. The median percentage change in angiomyolipoma (AML) volume was +7.6% (IQR -1.8% to +42.6%) for the placebo group and +8.9% (IQR 1.3% to 19.5%) for the metformin group (p = 0.28). Twenty-seven patients had SEGAs: 13 received placebo and 14 metformin. The median percentage change in SEGA volume was +3.0% (IQR -22.8% to +27.7%) for the placebo group and – 20.8% (IQR – 47.1% to - 5.0%) for the metformin group (p = 0.03). Twenty-one patients were assessed for seizure frequency: 9 received placebo and 12 received metformin. In the metformin group, a mean reduction of 43.7% from baseline in seizures was observed and in the placebo group a 3.1% mean reduction was observed, with a difference in response of 40.6% (95% CI -3.1% to +84.2%, p = 0.03). There were no significant differences between metformin and placebo groups for the other secondary outcomes. There were no deaths. Three serious adverse events (SAEs) occurred during the trial (all patients on metformin). / Interpretation: Metformin did not reduce AML volume. Metformin did reduce SEGA volume and seizure frequency compared with placebo. There may be a role for metformin in slowing or reversing growth of some life-threatening hamartomas in TSC and for reducing seizure frequency. Further study is justified. / Funding: This study was funded by the National Institute for Health and Research (NIHR) through the The Research for Patient Benefit Programme (RfPB)

Prognostic Value of D-Dimer and Markers of Coagulation for Stratification of Abdominal Aortic Aneurysm growth

Abdominal aortic aneurysm (AAA) is associated with high morbidity and mortality and is an established cause of unbalanced hemostasis. A number of hemostatic biomarkers have been associated with AAA; however, the utility of hemostatic biomarkers in AAA diagnosis and prognosis is unclear. The aim of the present study was to characterize the potential prognostic value of D-dimer and markers of altered hemostasis in a large cohort of patients with AAAs characterized by either fast or slow aneurysm growth (frequency matched for baseline diameter) and subaneurysmal dilations. We measured plasma concentrations of thrombin-antithrombin (TAT) complex, platelet factor 4 (PF4), and D-dimer in 352 patients with either fast-growing AAAs (.2 mm/y), slow-growing AAAs (,2 mm/y), subaneurysmal aortic dilations, or nonaneurysmal aortas. Plasma D-dimer and TAT were significantly elevated in both AAA and subaneurysmal dilation patients compared with controls. Individuals with D-dimer levels $500 ng/mL had 3.09 times the odds of subaneurysms, 6.23 times the odds of slow-growing AAAs, and 7.19 times the odds of fast-growing AAAs than individuals with D-dimer level,500 ng/mL. However, no differences in D-dimer concentration were noted between fast- and slow-growing aneurysms. Plasma D-dimer and TAT were strong independent predictors of AAA growth rate with multivariate analysis revealing a 500-ng/mL increase in D-dimer or 1-mg/mL increase in TAT led to additional 0.21-mm and 0.24-mm changes in aortic diameter per year, respectively. Rising levels of plasma TAT, in addition to D-dimer, may predict disease progression and aneurysm growth in patients with AAA or subaneurysmal dilation

A Novel Form of Chondrocyte Stress is Triggered by a COMP Mutation Causing Pseudoachondroplasia

Pseudoachondroplasia (PSACH) results from mutations in cartilage oligomeric matrix protein (COMP) and the p.D469del mutation within the type III repeats of COMP accounts for approximately 30% of PSACH. To determine disease mechanisms of PSACH in vivo, we introduced the Comp D469del mutation into the mouse genome. Mutant animals were normal at birth but grew slower than their wild-type littermates and developed short-limb dwarfism. In the growth plates of mutant mice chondrocyte columns were reduced in number and poorly organized, while mutant COMP was retained within the endoplasmic reticulum (ER) of cells. Chondrocyte proliferation was reduced and apoptosis was both increased and spatially dysregulated. Previous studies on COMP mutations have shown mutant COMP is co-localized with chaperone proteins, and we have reported an unfolded protein response (UPR) in mouse models of PSACH-MED (multiple epiphyseal dysplasia) harboring mutations in Comp (T585M) and Matn3, Comp etc (V194D). However, we found no evidence of UPR in this mouse model of PSACH. In contrast, microarray analysis identified expression changes in groups of genes implicated in oxidative stress, cell cycle regulation, and apoptosis, which is consistent with the chondrocyte pathology. Overall, these data suggest that a novel form of chondrocyte stress triggered by the expression of mutant COMP is central to the pathogenesis of PSACH. Hum Mutat 33:218–231, 2012. © 2011 Wiley Periodicals, Inc

Interventions to improve perinatal outcomes among migrant women in high-income countries: a systematic review protocol

INTRODUCTION: Women who are migrants and who are pregnant or postpartum are at high risk of poorer perinatal outcomes compared with host country populations due to experiencing numerous additional stressors including social exclusion and language barriers. High-income countries (HICs) host many migrants, including forced migrants who may face additional challenges in the peripartum period. Although HICs' maternity care systems are often well developed, they are not routinely tailored to the needs of migrant women. The primary objective will be to determine what interventions exist to improve perinatal outcomes for migrant women in HICs. The secondary objective will be to explore the effectiveness of these interventions by exploring the impact on perinatal outcomes. The main outcomes of interest will be rates of preterm birth, birth weight, and number of antenatal or postnatal appointments attended. METHODS AND ANALYSIS: This protocol follows the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Protocols guidelines. EMBASE, EMCARE, MEDLINE and PsycINFO, CENTRAL, Scopus, CINAHL Plus, and Web of Science, as well as grey literature sources will be searched from inception up to December 2022. We will include randomised controlled trials, quasi-experimental and interventional studies of interventions, which aim to improve perinatal outcomes in any HIC. There will be no language restrictions. We will exclude studies presenting only qualitative outcomes and those including mixed populations of migrant and non-migrant women. Screening and data extraction will be completed by two independent reviewers and risk of bias will be assessed using the Quality Assessment Tool for Quantitative Studies. If a collection of suitably comparable outcomes is retrieved, we will perform meta-analysis applying a random effects model. Presentation of results will comply with guidelines in the Cochrane Handbook of Systematic Reviews of Interventions and the PRISMA statement. ETHICS AND DISSEMINATION: Ethical approval is not required. Results will be submitted for peer-reviewed publication and presented at national and international conferences. The findings will inform the work of the Lancet Migration European Hub. PROSPERO REGISTRATION NUMBER: CRD42022380678

Retinal Morphometric Markers of Crystallized and Fluid Intelligence Among Adults With Overweight and Obesity

Objective: To investigate the relationship between retinal morphometric measures and intellectual abilities among adults with overweight and obesity.Methods: Adults between 25 and 45 years (N = 55, 38 females) with overweight or obesity (BMI ≥ 25.0 kg/m2) underwent an optical coherence tomography (OCT) scan to assess retinal nerve fiber layer (RNFL) volume, ganglion cell layer (GCL) volume, macular volume, and central foveal thickness. Dual-Energy X-ray absorptiometry was used to assess whole-body adiposity (% Fat). The Kaufman Brief Intelligence Test-2 was used to assess general intelligence (IQ), fluid, and crystallized intelligence. Hierarchical linear regression analyses were performed to examine relationships between adiposity and intelligence measures following adjustment of relevant demographic characteristics and degree of adiposity (i.e., % Fat).Results: Although initial bivariate correlations indicated that % Fat was inversely related to fluid intelligence, this relationship was mitigated by inclusion of other demographic factors, including age, sex, and education level. Regression analyses for primary outcomes revealed that RNFL was positively related to IQ and fluid intelligence. However, only GCL was positively related to crystallized intelligence.Conclusion: This work provides novel data linking specific retinal morphometric measures – assessed using OCT – to intellectual abilities among adults with overweight and obesity.Clinical Trial Registration:www.clinicaltrials.gov, identifier NCT02740439

Performance of empirical and model-based classifiers for detecting sucrase-isomaltase inhibition using the 13C-sucrose breath test

The 13C-sucrose breath test (13C-SBT) has been proposed to estimate sucrase-isomaltase (SIM) activity and is a promising test for SIM deficiency, which can cause gastrointestinal symptoms, and for intestinal mucosal damage caused by gut dysfunction or chemotherapy. We previously showed how various summary measures of the 13C-SBT breath curve reflect SIM inhibition. However, it is uncertain how the performance of these classifiers is affected by test duration. We leveraged 13C-SBT data from a cross-over study in 16 adults who received 0, 100, and 750 mg of Reducose, an SIM inhibitor. We evaluated the performance of a pharmacokinetic-model-based classifier, p, and three empirical classifiers (cumulative percent dose recovered at 90 min (cPDR90), time to 50% dose recovered, and time to peak dose recovery rate), as a function of test duration using receiver operating characteristic (ROC) curves. We also assessed the sensitivity, specificity, and accuracy of consensus classifiers. Test durations of less than 2 h generally failed to accurately predict later breath curve dynamics. The cPDR90 classifier had the highest ROC area-under-the-curve and, by design, was robust to shorter test durations. For detecting mild SIM inhibition, p had a higher sensitivity. We recommend 13C-SBT tests run for at least a 2 h duration. Although cPDR90 was the classifier with highest accuracy and robustness to test duration in this application, concerns remain about its sensitivity to misspecification of the CO2 production rate. More research is needed to assess these classifiers in target populations