Effects of once-weekly semaglutide on appetite, energy intake, control of eating, food preference and body weight in subjects with obesity.

AIM: To investigate the mechanism of action for body weight loss with semaglutide. MATERIALS AND METHODS: This randomised, double-blind, placebo-controlled, two-period crossover trial investigated the effects of 12 weeks treatment with once-weekly subcutaneous semaglutide, dose-escalated to 1.0 mg, in 30 subjects with obesity. Ad libitum energy intake, ratings of appetite, thirst, nausea and well-being, control of eating, food preference, resting metabolic rate, body weight and body composition were assessed. RESULTS: After a standardised breakfast, semaglutide, compared with placebo, led to a lower ad libitum energy intake during lunch (-1255 kJ; P < 0.0001), and during the subsequent evening meal (P = 0.0401) and snacks (P = 0.0034), resulting in a 24% reduction in total energy intake across all ad libitum meals throughout the day (-3036 kJ; P < 0.0001). Fasting overall appetite suppression scores were improved with semaglutide versus placebo, while nausea ratings were similar. Semaglutide was associated with less hunger and food cravings, better control of eating and a lower preference for high-fat foods. Resting metabolic rate, adjusted for lean body mass, did not differ between treatments. Semaglutide led to a reduction from baseline in mean body weight of 5.0 kg, predominantly from body fat mass. CONCLUSION: After 12 weeks' treatment, ad libitum energy intake was substantially lower with semaglutide versus placebo with a corresponding loss of body weight observed with semaglutide. In addition to reduced energy intake, likely mechanisms for semaglutide-induced weight loss included less appetite and food cravings, better control of eating and lower relative preference for fatty, energy-dense foods

With a biomechanical treatment in knee osteoarthritis, less knee pain did not correlate with synovitis reduction

© 2017 The Author(s). Background: Braces are used to treat pain in patellofemoral joint osteoarthritis (PFJOA). In a trial, we previously reported pain improvement after 6-weeks brace use. The pain reduction did not correlate with changes in Magnetic Resonance Imaging (MRI) assessed Bone Marrow Lesion volume or static synovial volume. Studies show that changes in the synovium on dynamic contrast enhanced (DCE) MRI are more closely associated with symptom change than static synovial volume changes. We hypothesised change in synovitis assessed using dynamic imaging could explain the reduction in pain. Method: One hundred twenty-six men and women aged 40-70 years with painful radiographically confirmed PFJOA were randomised to either brace wearing or no brace for 6-weeks. Pain assessment and DCE-MRI were performed at baseline and 6 weeks. DCE data was analysed using Tofts's equation. Pain measures included a VAS of pain on nominated aggravating activity (VAS NA ), and the KOOS pain subscale. Paired t-tests were used to determine within person change in outcome measures and Spearman's correlation coefficients were used to determine the correlation between change in pain and change in the DCE parameters. Results: Mean age of subjects was 55.5 years (SD = 7.5) and 57% were female. There was clear pain improvement in the brace users compared to controls (VAS NA - 16.87 mm, p = < 0.001). There was no significant change to the dynamic synovitis parameters among brace users nor was pain change correlated with change in dynamic synovitis parameters. Conclusion: The reduction in knee pain following brace wearing in patients with PFJOA is not explained by changes in synovitis. Trial registration: Trial registration number UK. ISRCTN50380458 /Registered 21.5.2010

Orientation and dynamics of transmembrane peptides: the power of simple models

In this review we discuss recent insights obtained from well-characterized model systems into the factors that determine the orientation and tilt angles of transmembrane peptides in lipid bilayers. We will compare tilt angles of synthetic peptides with those of natural peptides and proteins, and we will discuss how tilt can be modulated by hydrophobic mismatch between the thickness of the bilayer and the length of the membrane spanning part of the peptide or protein. In particular, we will focus on results obtained on tryptophan-flanked model peptides (WALP peptides) as a case study to illustrate possible consequences of hydrophobic mismatch in molecular detail and to highlight the importance of peptide dynamics for the experimental determination of tilt angles. We will conclude with discussing some future prospects and challenges concerning the use of simple peptide/lipid model systems as a tool to understand membrane structure and function

Ecological commonalities among pelagic fishes: comparison of freshwater ciscoes and marine herring and sprat

Systematic comparisons of the ecology between functionally similar fish species from freshwater and marine aquatic systems are surprisingly rare. Here, we discuss commonalities and differences in evolutionary history, population genetics, reproduction and life history, ecological interactions, behavioural ecology and physiological ecology of temperate and Arctic freshwater coregonids (vendace and ciscoes, Coregonus spp.) and marine clupeids (herring, Clupea harengus, and sprat, Sprattus sprattus). We further elucidate potential effects of climate warming on these groups of fish based on the ecological features of coregonids and clupeids documented in the previous parts of the review. These freshwater and marine fishes share a surprisingly high number of similarities. Both groups are relatively short-lived, pelagic planktivorous fishes. The genetic differentiation of local populations is weak and seems to be in part correlated to an astonishing variability of spawning times. The discrete thermal window of each species influences habitat use, diel vertical migrations and supposedly also life history variations. Complex life cycles and preference for cool or cold water make all species vulnerable to the effects of global warming. It is suggested that future research on the functional interdependence between spawning time, life history characteristics, thermal windows and genetic differentiation may profit from a systematic comparison of the patterns found in either coregonids or clupeids

Monitoring total-body inflammation and damage in joints and entheses: the first follow-up study of whole-body magnetic resonance imaging in rheumatoid arthritis

<p><b>Objective</b>: To investigate changes in whole-body magnetic resonance imaging (WBMRI) inflammatory and structural lesions in most joints and entheses in patients with rheumatoid arthritis (RA) treated with adalimumab.</p> <p><b>Methods</b>: WBMRI was obtained at weeks 0, 6, 16, and 52 in a 52 week follow-up study of 37 RA patients starting treatment with adalimumab. Readability and reliability of WBMRI were investigated for 76 peripheral joints, 23 discovertebral units, the sacroiliac joints, and 33 entheses. Changes in WBMRI joint and entheses counts were investigated.</p> <p><b>Results</b>: The readability of peripheral and axial joints was 82–100%, being less for elbows and small joints of the feet. For entheses, 72–100% were readable, except for entheses at the anterior chest wall, elbow, knee, and plantar fascia. The intrareader agreement was high for bone marrow oedema (BMO), bone erosion (80–100%), and enthesitis (77–100%), and slightly lower for synovitis and soft tissue inflammation (50–100%). All synovitis, BMO, and soft tissue inflammation counts decreased numerically during treatment. The 26-joint synovitis WBMRI count decreased significantly during the first 16 weeks for patients with a good European League Against Rheumatism (EULAR) response (from median 6 to 4, p < 0.05), but not for patients with a moderate or no EULAR response. There were no overall changes in structural lesions.</p> <p><b>Conclusions</b>: WBMRI allows simultaneous monitoring of most axial and peripheral joints and entheses in RA patients and can visualize a decrease in inflammatory counts during treatment. This first WBMRI follow-up study of patients with RA encourages further investigation of the usefulness of WBMRI in RA.</p