Obesity: when is specialist referral needed?

Obesity is a chronic progressive condition affecting 27% of the UK adult population. Obesity underlies much of primary care workload: 44% of type 2 diabetes (T2D) cases, 23% of ischaemic heart disease, and 41% of certain cancers are attributable to excess BMI.1 Worryingly, the number of adults with severe obesity, which significantly reduces life expectancy, has doubled to approximately 2.6 million over the past decade. Obesity and related illnesses lead to significant healthcare costs, estimated at £6.1 billion per year in the UK, with additional societal costs of £27 billion from reduced productivity secondary to obesity-related ill-health.

Potential mechanisms underlying the effect of bariatric surgery on eating behaviour

PURPOSE OF REVIEW: Reduced energy intake, resulting from favourable changes in eating behaviour, is the predominant driver of weight loss following bariatric surgery. Here we review the most recent studies examining the impact of Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy, the two most common bariatric procedures, upon eating behaviour and the suggested underlying biological mechanisms. RECENT FINDINGS: Following RYGB or sleeve gastrectomy, most people report subjective changes in appetite, taste and food preference, with decreased high-fat preference most commonly reported. Objective postsurgery changes in taste and olfactory acuity occur. A new phenomenon, 'meal-size aversion', may contribute to reduced postoperative energy intake. Recent studies provide evidence for peptide YY3-36, glucagon-like peptide-1, ghrelin, neurotensin and oleoylethanolamide as mediators of postoperative eating behaviour changes. Factors modulating these changes include sex, type 2 diabetes status, genetics and bariatric procedure. New studies implicate central dopaminergic and opioid receptor signalling as key neural mediators driving altered eating behaviour. Brain neuroimaging studies show that obesity-associated changes in food-cue responses, brain connectivity and structural abnormalities are normalized following bariatric surgery. SUMMARY: Understanding the biological mechanisms mediating the eating behaviour changes engendered by bariatric surgery may lead to the development of novel therapeutic strategies for people with obesity

A study protocol for a randomised crossover study evaluating the effect of diets differing in carbohydrate quality on ileal content and appetite regulation in healthy humans

A major component of the digesta reaching the colon from the distal ileum is carbohydrate. This carbohydrate is subject to microbial fermentation and can radically change bacterial populations in the colon and the metabolites they produce, particularly short-chain fatty acids (SCFA). However, very little is currently known about the forms and levels of carbohydrate in the ileum and the composition of the ileal microbiota in humans. Most of our current understanding of carbohydrate that is not absorbed by the small intestine comes from ileostomy models, which may not reflect the physiology of an intact gastrointestinal tract. We will investigate how ileal content changes depending on diet using a randomised crossover study in healthy humans. Participants will be inpatients at the research facility for three separate 4-day visits. During each visit, participants will consume one of three diets, which differ in carbohydrate quality: 1) low-fibre refined diet; 2) high-fibre diet with intact cellular structures; 3) high-fibre diet where the cellular structures have been disrupted (e.g. milling, blending). On day 1, a nasoenteric tube will be placed into the distal ileum and its position confirmed under fluoroscopy. Ileal samples will be collected via the nasoenteric tube and metabolically profiled, which will determine the amount and type of carbohydrate present, and the composition of the ileal microbiota will be measured. Blood samples will be collected to assess circulating hormones and metabolites. Stool samples will be collected to assess faecal microbiota composition. Subjective appetite measures will be collected using visual analogue scales. Breath hydrogen will be measured in real-time as a marker of intestinal fermentation. Finally, an continuous fermentation model will be inoculated with ileal fluid in order to understand the shift in microbial composition and SCFA produced in the colon following the different diets. ISRCTN11327221. [Abstract copyright: Copyright: © 2019 Byrne CS et al.

Ttk69-dependent repression of lozenge prevents the ectopic development of R7 cells in the Drosophila larval eye disc

Background: During the development of the Drosophila eye, specific cell types differentiate from an initially equipotent group of uncommitted precursor cells. The lozenge (lz) gene, which is a member of the Runt family of transcriptional regulators, plays a pivotal role in mediating this process through regulating the expression of several fate-specifying transcription factors. However, the regulation of lz, and the control of lz expression levels in different cell types is not fully understood. Results: Here, we show a genetic interaction between Tramtrack69 (Ttk69) a key transcriptional repressor and an inhibitor of neuronal fate specification, and lz, the master patterning gene of cells posterior to the morphogenetic furrow in the Drosophila eye disc. Loss of Ttk69 expression causes the development of ectopic R7 cells in the third instar eye disc, with these cells being dependent upon Lz for their development. Using the binary UAS Gal4 system, we show that overexpression of Ttk69 causes the loss of lz-dependent differentiating cells, and a down-regulation of Lz expression in the developing eye. The loss of lz-dependent cells can be rescued by overexpressing lz via a GMR-lz transgene. We provide additional data showing that factors functioning upstream of Ttk69 in eye development regulate lz in a Ttk69-dependent manner. Conclusions: Our results lead us to conclude that Ttk69 can either directly or indirectly repress lz gene expression to prevent the premature development of R7 precursor cells in the developing eye of Drosophila. We therefore define a mechanism for the tight regulatory control of the master pre-patterning gene, lz, in early Drosophila eye development and provide insight into how differential levels of lz expression can be achieved to effect specific cell fate outcomes

Spatiotemporal slope stability analytics for failure estimation (SSSAFE): linking radar data to the fundamental dynamics of granular failure

Impending catastrophic failure of granular earth slopes manifests distinct kinematic patterns in space and time. While risk assessments of slope failure hazards have routinely relied on the monitoring of ground motion, such precursory failure patterns remain poorly understood. A key challenge is the multiplicity of spatiotemporal scales and dynamical regimes. In particular, there exist a precursory failure regime where two mesoscale mechanisms coevolve, namely, the preferred transmission paths for force and damage. Despite extensive studies, a formulation which can address their coevolution not just in laboratory tests but also in large, uncontrolled field environments has proved elusive. Here we address this problem by developing a slope stability analytics framework which uses network flow theory and mesoscience to model this coevolution and predict emergent kinematic clusters solely from surface ground motion data. We test this framework on four data sets: one at the laboratory scale using individual grain displacement data; three at the field scale using line-of-sight displacement of a slope surface, from ground-based radar in two mines and from space-borne radar for the 2017 Xinmo landslide. The dynamics of the kinematic clusters deliver an early prediction of the geometry, location and time of failure

The grounded psychometric development and initial validation of the Health Literacy Questionnaire (HLQ)

BACKGROUND: Health literacy has become an increasingly important concept in public health. We sought to develop a comprehensive measure of health literacy capable of diagnosing health literacy needs across individuals and organisations by utilizing perspectives from the general population, patients, practitioners and policymakers. METHODS: Using a validity-driven approach we undertook grounded consultations (workshops and interviews) to identify broad conceptually distinct domains. Questionnaire items were developed directly from the consultation data following a strict process aiming to capture the full range of experiences of people currently engaged in healthcare through to people in the general population. Psychometric analyses included confirmatory factor analysis (CFA) and item response theory. Cognitive interviews were used to ensure questions were understood as intended. Items were initially tested in a calibration sample from community health, home care and hospital settings (N=634) and then in a replication sample (N=405) comprising recent emergency department attendees. RESULTS: Initially 91 items were generated across 6 scales with agree/disagree response options and 5 scales with difficulty in undertaking tasks response options. Cognitive testing revealed that most items were well understood and only some minor re-wording was required. Psychometric testing of the calibration sample identified 34 poorly performing or conceptually redundant items and they were removed resulting in 10 scales. These were then tested in a replication sample and refined to yield 9 final scales comprising 44 items. A 9-factor CFA model was fitted to these items with no cross-loadings or correlated residuals allowed. Given the very restricted nature of the model, the fit was quite satisfactory: χ(2)(WLSMV)(866 d.f.) = 2927, p<0.000, CFI = 0.936, TLI = 0.930, RMSEA = 0.076, and WRMR = 1.698. Final scales included: Feeling understood and supported by healthcare providers; Having sufficient information to manage my health; Actively managing my health; Social support for health; Appraisal of health information; Ability to actively engage with healthcare providers; Navigating the healthcare system; Ability to find good health information; and Understand health information well enough to know what to do. CONCLUSIONS: The HLQ covers 9 conceptually distinct areas of health literacy to assess the needs and challenges of a wide range of people and organisations. Given the validity-driven approach, the HLQ is likely to be useful in surveys, intervention evaluation, and studies of the needs and capabilities of individuals

Effect of diet or diet plus physical activity versus usual care on inflammatory markers in patients with newly diagnosed type 2 diabetes: The Early ACTivity in Diabetes (ACTID) randomized, controlled trial

This is the final version. Available on open access from Wiley via the DOI in this recordBACKGROUND: Inflammation plays a major role in diabetes-associated cardiovascular disease (CVD). There is uncertainty whether diet and physical activity interventions can be successfully integrated into healthcare settings and reduce markers of inflammation and risk of CVD in patients with type 2 diabetes (T2D). METHODS AND RESULTS: Systemic markers of inflammation were determined in a 12-month, real-world, multicenter, randomized, controlled trial that investigated the effect of diet, diet plus physical activity, and usual care in 593 individuals with newly diagnosed T2D. During the first 6 months, serum C-reactive protein (CRP) improved by -21 (-36 to -1.4)% and -22 (-38 to -3.1)% in diet and diet plus physical activity arms versus usual care. There were also improvements in adiponectin and soluble intercellular adhesion molecule-1 (sICAM-1). Though medication-adjusted CRP was improved between 6 and 12 months for usual care, both interventions were more successful in reducing the relative risk of a high-risk CRP level of >3 mg/L (risk ratios of 0.72 [0.55 to 0.95] for diet versus usual care and 0.67 [0.50 to 0.90] for diet plus activity versus usual care). Furthermore, sICAM-1 (a marker of vascular risk), remained substantially lower than usual care in both intervention arms at 12 months. CONCLUSIONS: Motivational, unsupervised diet and/or diet plus physical activity interventions given soon after diagnosis in real-world healthcare settings improve markers of inflammation and cardiovascular risk in patients with T2D, even after accounting for the effect of adjustments to medication to try and control blood pressure, glycated hemoglobin, and lipids. CLINICAL TRIAL REGISTRATION URL: http://www.controlled-trials.com/. Unique identifier: ISRCTN92162869.British Heart FoundationDiabetes UKUK Department of Healt