Aspects of Obesity: From aetiology to weight loss and maintenance

Introduction Obesity is a significant global health and financial issue with prevalence increasing. While the cornerstone of its management remains a combined lifestyle intervention, weight loss recidivism is high. Recent novel insights relating to dietary protein and to weight homeostasis and neuro-endocrine adaptation shed light on these important aspects of obesity. Results Experiment 1 demonstrated that in lean health adults, after 4 days of ad libitum diets followed by a standardised breakfast, the lowest %protein diet was associated with highest fasting ghrelin and lowest post-prandial cholecystokinin. Experiment 2 demonstrated that both obese and lean mice varied daily food intake by >12% when consuming low protein compared to high protein chow. Experiment 3 demonstrated in obese adults that weight loss by combined lifestyle intervention was associated with reduced fasting ghrelin and glucagon-like peptide-1. Discussion The intake for dietary protein is prioritised even at the expense of increased total energy consumption and the physiological effects of changes to gut hormones on low protein diets is to favour hunger. The secular trend of reduced energy intake by protein may be a key driver towards obesity. Weight regain after lifestyle interventions are due to changes in mediators of appetite and body weight rather than just a failure of behaviour. These results challenge the conventional understanding about obesity

Utilisation of the 2019 IWGDF diabetic foot infection guidelines to benchmark practice and improve the delivery of care in persons with diabetic foot infections

Aims: To utilise the 2019 International Working Group on the Diabetic Foot (IWGDF) - diabetic foot infection (DFI) guidelines as an audit tool for clinical practice in patients with diabetes attending a High-Risk Foot Service. Methods: Data from 93 consecutive patients were collected over a 19-month period in patients attending a High-Risk Foot Service. The diagnosis and management of each patient in the sample were compared against the 2019 IWGDF DFI guidelines, grouped into four categories: Diagnosis, Microbiology, Treatment of soft tissue infection, and Surgical treatment and osteomyelitis. Deficits in performance were recorded using the recommendations as a benchmark standard. Results: There were 109 DFI events. Nineteen (63%) of the recommendations were met, 7 (24%) were partially met, and four (13%) recommendations were not met. Fourteen of the sample had no documented requests for full blood counts. Tissue was obtained for culture in 32 (29%) of the sample. No percutaneous bone biopsies were performed. Only 13 (28%) patients had intraoperative bone specimens sent for culture and sensitivities, with no bone specimens sent for histopathology. Modification of antibiotic therapy following available culture results was low, occurring in 12 out of 63 possible occasions (19%). The duration of antibiotic regimens in PEDIS 2 infections and osteomyelitis was greater than that recommended. Conclusions: Utilising the IWGDF DFI guidelines to benchmark clinical practice is a useful tool to identify gaps in clinical performance or service delivery and may help to improve patient care

Testing Protein Leverage in Lean Humans: A Randomised Controlled Experimental Study

A significant contributor to the rising rates of human obesity is an increase in energy intake. The ‘protein leverage hypothesis’ proposes that a dominant appetite for protein in conjunction with a decline in the ratio of protein to fat and carbohydrate in the diet drives excess energy intake and could therefore promote the development of obesity. Our aim was to test the ‘protein leverage hypothesis’ in lean humans by disguising the macronutrient composition of foods offered to subjects under ad libitum feeding conditions. Energy intakes and hunger ratings were measured for 22 lean subjects studied over three 4-day periods of in-house dietary manipulation. Subjects were restricted to fixed menus in random order comprising 28 foods designed to be similar in palatability, availability, variety and sensory quality and providing 10%, 15% or 25% energy as protein. Nutrient and energy intake was calculated as the product of the amount of each food eaten and its composition. Lowering the percent protein of the diet from 15% to 10% resulted in higher (+12±4.5%, p = 0.02) total energy intake, predominantly from savoury-flavoured foods available between meals. This increased energy intake was not sufficient to maintain protein intake constant, indicating that protein leverage is incomplete. Urinary urea on the 10% and 15% protein diets did not differ statistically, nor did they differ from habitual values prior to the study. In contrast, increasing protein from 15% to 25% did not alter energy intake. On the fourth day of the trial, however, there was a greater increase in the hunger score between 1–2 h after the 10% protein breakfast versus the 25% protein breakfast (1.6±0.4 vs 25%: 0.5±0.3, p = 0.005). In our study population a change in the nutritional environment that dilutes dietary protein with carbohydrate and fat promotes overconsumption, enhancing the risk for potential weight gain

Effects of Cannabidiol on exercise physiology and bioenergetics : a randomised controlled pilot trial

Background: Cannabidiol (CBD) has demonstrated anti-inflammatory, analgesic, anxiolytic and neuroprotective effects that have the potential to benefit athletes. This pilot study investigated the effects of acute, oral CBD treatment on physiological and psychological responses to aerobic exercise to determine its practical utility within the sporting context. Methods: On two occasions, nine endurance-trained males (mean±SD V̇O2max: 57.4±4.0 mL·min−1 ·kg−1 ) ran for 60 min at a fixed intensity (70% V̇O2max) (RUN 1) before completing an incremental run to exhaustion (RUN 2). Participants received CBD (300 mg; oral) or placebo 1.5 h before exercise in a randomised, double-blind design. Respiratory gases (V̇O2), respiratory exchange ratio (RER), heart rate (HR), blood glucose (BG) and lactate (BL) concentrations, and ratings of perceived exertion (RPE) and pleasure–displeasure were measured at three timepoints (T1–3) during RUN 1. V̇O2max, RERmax, HRmax and time to exhaustion (TTE) were recorded during RUN 2. Venous blood was drawn at Baseline, Pre- and Post-RUN 1, Post-RUN 2 and 1 h Post-RUN 2. Data were synthesised using Cohen’s dz effect sizes and 85% confidence intervals (CIs). Effects were considered worthy of further investigation if the 85% CI included±0.5 but not zero. Results: CBD appeared to increase V̇O2 (T2:+38±48 mL·min−1, dz: 0.25–1.35), ratings of pleasure (T1:+0.7±0.9, dz: 0.22–1.32; T2:+0.8±1.1, dz: 0.17–1.25) and BL (T2:+3.3±6.4 mmol·L−1, dz:>0.00–1.03) during RUN 1 compared to placebo. No differences in HR, RPE, BG or RER were observed between treatments. CBD appeared to increase V̇O2max (+119±206 mL·min−1, dz: 0.06–1.10) and RERmax (+0.04±0.05 dz: 0.24–1.34) during RUN 2 compared to placebo. No differences in TTE or HRmax were observed between treatments. Exercise increased serum interleukin (IL)-6, IL-1β, tumour necrosis factor-α, lipopolysaccharide and myoglobin concentrations (i.e. Baseline vs. Post-RUN 1, Post-RUN 2 and/or 1-h Post-RUN 2, p’s<0.05). However, the changes were small, making it difficult to reliably evaluate the effect of CBD, where an effect appeared to be present. Plasma concentrations of the endogenous cannabinoid, anandamide (AEA), increased Post-RUN 1 and Post-RUN 2, relative to Baseline and Pre-RUN 1 (p’s<0.05). CBD appeared to reduce AEA concentrations Post-RUN 2, compared to placebo (−0.95±0.64 pmol·mL−1, dz: −2.19, −0.79). Conclusion: CBD appears to alter some key physiological and psychological responses to aerobic exercise without impairing performance. Larger studies are required to confirm and better understand these preliminary findings

THE STYLE OF LATE CENOZOIC DEFORMATION AT THE EASTERN FRONT OF THE CALIFORNIA COAST RANGES

The 1983 Coalinga earthquake occurred at the eastern boundary of the California Coast Ranges in response to northeast directed thrusting. Such movements over the past 2 Ma have produced Coalinga anticline by folding above the blind eastern tip of the Coalinga thrust zone. The 600-km length of the Coast Ranges boundary shares a common structural setting that involves westward upturn of Cenozoic and Cretaceou strata at the eastern front of the Coast Ranges and a major, southwest facing step in the basement surface beneath the western Great Valley. Like Coalinga anticline, Pliocene and Quaternary folding and faulting along the rest of the boundary also result from northeast-southwest compression acting nearly perpendicular to the strike of the San Andreas fault. We suggest that much of this deformation is related to active thrusts beneath the eastern Coast Ranges. The step in the basement surface beneath the Great Valley seems to have controlled the distribution of this deformation and the shape of the Coast Ranges boundary

The effect of illustrations on patient comprehension of medication instruction labels

BACKGROUND: Labels with special instructions regarding how a prescription medication should be taken or its possible side effects are often applied to pill bottles. The goal of this study was to determine whether the addition of illustrations to these labels affects patient comprehension. METHODS: Study participants (N = 130) were enrolled by approaching patients at three family practice clinics in Toronto, Canada. Participants were asked to interpret two sets of medication instruction labels, the first with text only and the second with the same text accompanied by illustrations. Two investigators coded participants' responses as incorrect, partially correct, or completely correct. Health literacy levels of participants were measured using a validated instrument, the REALM test. RESULTS: All participants gave a completely correct interpretation for three out of five instruction labels, regardless of whether illustrations were present or not. For the two most complex labels, only 34–55% of interpretations of the text-only version were completely correct. The addition of illustrations was associated with improved performance in 5–7% of subjects and worsened performance in 7–9% of subjects. CONCLUSION: The commonly-used illustrations on the medication labels used in this study were of little or no use in improving patients' comprehension of the accompanying written instructions

Unified Structural Representation of the southern California crust and upper mantle

We present a new, 3D description of crust and upper mantle velocity structure in southern California implemented as a Unified Structural Representation (USR). The USR is comprised of detailed basin velocity descriptions that are based on tens of thousands of direct velocity (Vp, Vs) measurements and incorporates the locations and displacement of major fault zones that influence basin structure. These basin descriptions were used to developed tomographic models of crust and upper mantle velocity and density structure, which were subsequently iterated and improved using 3D waveform adjoint tomography. A geotechnical layer (GTL) based on Vs30 measurements and consistent with the underlying velocity descriptions was also developed as an optional model component. The resulting model provides a detailed description of the structure of the southern California crust and upper mantle that reflects the complex tectonic history of the region. The crust thickens eastward as Moho depth varies from 10 to 40 km reflecting the transition from oceanic to continental crust. Deep sedimentary basins and underlying areas of thin crust reflect Neogene extensional tectonics overprinted by transpressional deformation and rapid sediment deposition since the late Pliocene. To illustrate the impact of this complex structure on strong ground motion forecasting, we simulate rupture of a proposed M 7.9 earthquake source in the Western Transverse Ranges. The results show distinct basin amplification and focusing of energy that reflects crustal structure described by the USR that is not captured by simpler velocity descriptions. We anticipate that the USR will be useful for a broad range of simulation and modeling efforts, including strong ground motion forecasting, dynamic rupture simulations, and fault system modeling. The USR is available through the Southern California Earthquake Center (SCEC) website (http://www.scec.org)