Increase in colonic PRopionate as a method of prEVENTing weight gain over 12 months in adults aged 20-40 years (iPREVENT): a multi-centre, double-blind, randomised, parallel-group trial.

Background: Obesity drives metabolic disease development. Preventing weight gain during early adulthood could mitigate later-life chronic disease risk. Increased dietary fibre intake, leading to enhanced colonic microbial fermentation and short-chain fatty acid (SCFA) production, is associated with lower body weight.

In vivo mRNA expression of a multi-mechanistic mAb combination protects against Staphylococcus aureus infection.

Single monoclonal antibodies (mAbs) can be expressed in vivo through gene delivery of their mRNA formulated with lipid nanoparticles (LNPs). However, delivery of a mAb combination could be challenging due to the risk of heavy and light variable chain mispairing. We evaluated the pharmacokinetics of a three mAb combination against Staphylococcus aureus first in single chain variable fragment scFv-Fc and then in immunoglobulin G 1 (IgG1) format in mice.

5-year follow-up of the randomised Diabetes Remission Clinical Trial (DiRECT) of continued support for weight loss maintenance in the UK: an extension study.

Background: In DiRECT, a randomised controlled effectiveness trial, weight management intervention after 2 years resulted in mean weight loss of 7·6 kg, with 36% of participants in remission of type 2 diabetes. Of 36 in the intervention group who maintained over 10 kg weight loss at 2 years, 29 (81%) were in remission. Continued low-intensity dietary support was then offered up to 5 years from baseline to intervention participants, aiming to maintain weight loss and gain clinical benefits.

Genomic Architecture Predicts Tree Topology, Population Structuring, and Demographic History in Amazonian Birds.

Geographic barriers are frequently invoked to explain genetic structuring across the landscape. However, inferences on the spatial and temporal origins of population variation have been largely limited to evolutionary neutral models, ignoring the potential role of natural selection and intrinsic genomic processes known as genomic architecture in producing heterogeneity in differentiation across the genome. To test how variation in genomic characteristics (e.

Protection against lung pathology during obesity-accelerated ageing in mice by the parasitic worm product ES-62.

Mice develop pathology in the lungs as they age and this may be accelerated by a high calorie diet (HCD). ES-62 is a protein secreted by the parasitic worm that is immunomodulatory by virtue of covalently attached phosphorylcholine (PC) moieties. In this study, we show that weekly treatment of C57BL/6J mice with ES-62 protected against pathology in the lungs in male but not female mice fed a HCD from 10 weeks of age as shown by reductions in cellular infiltration and airway remodelling, particularly up to 160 days of age.

Habitat specialization predicts demographic response and vulnerability of floodplain birds in Amazonia.

The annual flooding cycle of Amazonian rivers sustains the largest floodplains on Earth, which harbour a unique bird community. Recent studies suggest that habitat specialization drove different patterns of population structure and gene flow in floodplain birds. However, the lack of a direct estimate of habitat affinity prevents a proper test of its effects on population histories.

Signal of harm in morphine use in adults with acute pulmonary oedema: A rapid systematic review.

Background: Heart failure affects nearly 65 million people globally, resulting in recurrent hospital admissions and substantial healthcare expenditure. The use of morphine in the management of acute pulmonary oedema remains controversial, with conflicting guidance and significant variation in practice. Synthesised evidence is needed to inform standard treatment guidelines and clinical practice.

Dietary weight-management for type 2 diabetes remissions in South Asians: the South Asian diabetes remission randomised trial for proof-of-concept and feasibility (STANDby).

Background: We aimed to assess whether a structured weight management programme incorporating a total diet replacement (TDR) (3-5 months ∼850 kcal/day formula diet) weight loss phase is acceptable to people of South Asian ethnicity and can achieve type 2 diabetes (T2D) remissions similarly to other populations.

Methods: Adults of South Asian ethnicity, aged 18-65 years, with T2D for ≤4 years, and BMI 25-45 kg/m were recruited from primary care and social media, and randomised to commence TDR either immediately (iTDR), or delayed (dTDR) for 3-5 months as a usual care control arm during this period. Intervention effects were tested in randomised comparisons powered to detect significant weight loss, and in an expanded observational analysis to determine remission effect size, including both iTDR and dTDR groups.

Physical activity, inactivity and sleep during the Diabetes Remission Clinical Trial (DiRECT).

Aims: As sustained weight loss is vital for achieving remission of type 2 diabetes, we explored whether randomisation to weight loss plus maintenance in the DiRECT trial was associated with physical activity, inactivity or sleep.

Methods: Participants were randomised to either a dietary weight management programme or best-practice care. The weight management group were encouraged to increase daily physical activity to their sustainable maximum.

Antibody-oligonucleotide conjugate achieves CNS delivery in animal models for spinal muscular atrophy.

Antisense oligonucleotides (ASOs) have emerged as one of the most innovative new genetic drug modalities. However, their high molecular weight limits their bioavailability for otherwise-treatable neurological disorders. We investigated conjugation of ASOs to an antibody against the murine transferrin receptor, 8D3130, and evaluated it via systemic administration in mouse models of the neurodegenerative disease spinal muscular atrophy (SMA).

Late Pleistocene landscape changes and habitat specialization as promoters of population genomic divergence in Amazonian floodplain birds.

Although vicariant processes are expected to leave similar genomic signatures among codistributed taxa, ecological traits such as habitat and stratum can influence genetic divergence within species. Here, we combined landscape history and habitat specialization to understand the historical and ecological factors responsible for current levels of genetic divergence in three species of birds specialized in seasonally flooded habitats in muddy rivers and which are widespread in the Amazon basin but have isolated populations in the Rio Branco. Populations of the white-bellied spinetail (Mazaria propinqua), lesser wagtail-tyrant (Stigmatura napensis) and bicolored conebill (Conirostrum bicolor) are currently isolated in the Rio Branco by the black-waters of the lower Rio Negro, offering a unique opportunity to test the effect of river colour as a barrier to gene flow.

Phylogenomic Analysis of the Parrots of the World Distinguishes Artifactual from Biological Sources of Gene Tree Discordance.

Gene tree discordance is expected in phylogenomic trees and biological processes are often invoked to explain it. However, heterogeneous levels of phylogenetic signal among individuals within data sets may cause artifactual sources of topological discordance. We examined how the information content in tips and subclades impacts topological discordance in the parrots (Order: Psittaciformes), a diverse and highly threatened clade of nearly 400 species.

Total Diet Replacement Within an Integrated Intensive Lifestyle Intervention for Remission of Type 2 Diabetes: Lessons From DiRECT.

The prognosis for people with type 2 diabetes (T2D) remains concerning, yet its seriousness is often underestimated. T2D is a manifestation, in susceptible individuals, of the disease-process of obesity, and at diagnosis, 10-year survival rates for T2D are around 50%. Here, we will examine: (a) the role of weight loss in T2D, (b) use of total diet replacements (TDRs) to induce weight loss, (c) the Diabetes Remission Clinical Trial (DiRECT) protocol and key results, (d) other dietary interventions related to T2D remission, (e) remission in real life, and (f) future directions.

River network rearrangements promote speciation in lowland Amazonian birds.

Large Amazonian rivers impede dispersal for many species, but lowland river networks frequently rearrange, thereby altering the location and effectiveness of river barriers through time. These rearrangements may promote biotic diversification by facilitating episodic allopatry and secondary contact among populations. We sequenced genome-wide markers to evaluate the histories of divergence and introgression in six Amazonian avian species complexes.

Delivering the Diabetes Remission Clinical Trial (DiRECT) in primary care: Experiences of healthcare professionals.

Objective: The Diabetes Remission Clinical Trial (DiRECT) used a formula total diet replacement programme followed by structured weight loss maintenance to induce and sustain weight loss and remission of type 2 diabetes (T2D) in 36% of participants after 2 years. Nurses and dietitians delivering DiRECT in 22 primary care practices in Tyneside and Scotland provided behavioural support to participants. Participant experiences with DiRECT highlighted the key role of support by healthcare professionals (HCPs).

Microevolutionary dynamics show tropical valleys are deeper for montane birds of the Atlantic Forest.

Tropical mountains hold more biodiversity than their temperate counterparts, and this disparity is often associated with the latitudinal climatic gradient. However, distinguishing the impact of latitude versus the background effects of species history and traits is challenging due to the evolutionary distance between tropical and temperate assemblages. Here, we test whether microevolutionary processes are linked to environmental variation across a sharp latitudinal transition in 21 montane birds of the southern Atlantic Forest in Brazil.

Participant experiences in the Diabetes REmission Clinical Trial (DiRECT).

Introduction: The Diabetes REmission Clinical Trial (DiRECT) has shown that sustained remission of type 2 diabetes in primary care is achievable through weight loss using total diet replacement (TDR) with continued behavioural support. Understanding participants' experiences can help optimise the intervention, support implementation into healthcare, and understand the process of behaviour change.

Methods: Thirty-four DiRECT participants were recruited into this embedded qualitative evaluation study.

Rugged relief and climate promote isolation and divergence between two neotropical cold-associated birds.

The role of historical factors in establishing patterns of diversity in tropical mountains is of interest to understand the buildup of megadiverse biotas. In these regions, the historical processes of range fragmentation and contraction followed by dispersal are thought to be mediated by the interplay between rugged relief (complex topography) and climate fluctuations and likely explain most of the dynamics of diversification in plants and animals. Although empirical studies addressing the interaction between climate and topography have provided invaluable insights into population divergence and speciation patterns in tropical montane organisms, a more detailed and robust test of such processes in an explicit spatio-temporal framework is still lacking.

Antihypertensive medication needs and blood pressure control with weight loss in the Diabetes Remission Clinical Trial (DiRECT).

Aims/hypothesis: Our aim was to evaluate the safety and efficacy of a planned therapeutic withdrawal of all antihypertensive and diuretic medications, on commencing a formula low-energy diet replacement, targeting remission of type 2 diabetes.

Methods: Post hoc analysis of changes in BP, antihypertensive medication prescriptions and symptoms during the initial total diet replacement phase was performed in the intervention arm of the Diabetes Remission Clinical Trial (n = 143) and in the subset (n = 69) who discontinued antihypertensive medications at the start of total diet replacement. The Counterweight-Plus total diet replacement provided about 3470 kJ/day (830 kcal) with automatic reductions in all nutrients, including sodium, to achieve marked negative energy balance and rapid weight loss over 12-20 weeks, with regular BP monitoring and an antihypertensive reintroduction protocol based on current clinical guidelines.

Brief formula low-energy-diet for relapse management during weight loss maintenance in the Diabetes Remission Clinical Trial (DiRECT).

Background: Weight loss maintenance (WLM) is critical for sustaining type 2 diabetes (T2D) remission, but poorly evidenced. We evaluated brief return to formula low-energy-diet (LED) as relapse treatments (RTs) during the WLM phase of the Diabetes Remission Clinical Trial (DiRECT).

Methods: This post-hoc evaluation included all participants commencing the WLM phase of DiRECT.

Weight loss-induced increase in fasting ghrelin concentration is a predictor of weight regain: Evidence from the Diabetes Remission Clinical Trial (DiRECT).

Aim: To investigate whether appetite-related hormones were predictors of weight regain in the Diabetes Remission Clinical Trial (DiRECT).

Materials And Methods: DiRECT is a cluster-randomized clinical trial, designed to assess the effect of weight loss on type 2 diabetes remission. For this post hoc analysis, data were available for 253 (147 interventions, 106 controls) individuals with type 2 diabetes (age 53.

'I have been all in, I have been all out and I have been everything in-between': A 2-year longitudinal qualitative study of weight loss maintenance.

Background: Qualitative studies investigating weight management experiences are usually cross-sectional or of short duration, which limits understanding of the long-term challenges.

Methods: Eleven women [mean (SD) age 44.9 (9.