Objective To assess the effectiveness of a range of weight management programmes in terms of weight loss.Design Eight arm randomised controlled trial. Setting Primary care trust in Birmingham, England.Participants 740 obese or overweight men and women with a comorbid disorder identified from general practice records.

Research into the biological role of the Ca2+-releasing second messenger NAADP (nicotinic acid adenine dinucleotide phosphate) has been hampered by a lack of chemical probes. To find new chemical probes for exploring NAADP signaling, we turned to virtual screening, which can evaluate millions of molecules rapidly and inexpensively. We used NAADP as the query ligand to screen the chemical library ZINC for compounds with 3D-shape and electrostatic similarity. We tested the top-ranking hits in a sea urchin egg bioassay and found that one hit, Ned-19, blocks NAADP signaling at nanomolar concentrations. In intact cells, Ned-19 blocked NAADP signaling and fluorescently labeled NAADP receptors. Moreover, we show the utility of Ned-19 as a chemical probe by using it to demonstrate that NAADP is a key causal link between glucose sensing and Ca2+ increases in mouse pancreatic beta cells.

SummaryBackgroundObesity is a common cause of non-communicable disease. Guidelines recommend that physicians screen and offer brief advice to motivate weight loss through referral to behavioural weight loss programmes. However, physicians rarely intervene and no trials have been done on the subject. We did this trial to establish whether physician brief intervention is acceptable and effective for reducing bodyweight in patients with obesity.MethodsIn this parallel, two-arm, randomised trial, patients who consulted 137 primary care physicians in England were screened for obesity. Individuals could be enrolled if they were aged at least 18 years, had a body-mass index of at least 30 kg/m2 (or at least 25 kg/m2 if of Asian ethnicity), and had a raised body fat percentage. At the end of the consultation, the physician randomly assigned participants (1:1) to one of two 30 s interventions. Randomisation was done via preprepared randomisation cards labelled with a code representing the allocation, which were placed in opaque sealed envelopes and given to physicians to open at the time of treatment assignment. In the active intervention, the physician offered referral to a weight management group (12 sessions of 1 h each, once per week) and, if the referral was accepted, the physician ensured the patient made an appointment and offered follow-up. In the control intervention, the physician advised the patient that their health would benefit from weight loss. The primary outcome was weight change at 12 months in the intention-to-treat population, which was assessed blinded to treatment allocation. We also assessed asked patients' about their feelings on discussing their weight when they have visited their general practitioner for other reasons. Given the nature of the intervention, we did not anticipate any adverse events in the usual sense, so safety outcomes were not assessed. This trial is registered with the ISRCTN Registry, number ISRCTN26563137.FindingsBetween June 4, 2013, and Dec 23, 2014, we screened 8403 patients, of whom 2728 (32%) were obese. Of these obese patients, 2256 (83%) agreed to participate and 1882 were eligible, enrolled, and included in the intention-to-treat analysis, with 940 individuals in the support group and 942 individuals in the advice group. 722 (77%) individuals assigned to the support intervention agreed to attend the weight management group and 379 (40%) of these individuals attended, compared with 82 (9%) participants who were allocated the advice intervention. In the entire study population, mean weight change at 12 months was 2·43 kg with the support intervention and 1·04 kg with the advice intervention, giving an adjusted difference of 1·43 kg (95% CI 0·89–1·97). The reactions of the patients to the general practitioners' brief interventions did not differ significantly between the study groups in terms of appropriateness (adjusted odds ratio 0·89, 95% CI 0·75–1·07, p=0·21) or helpfulness (1·05, 0·89–1·26, p=0·54); overall, four (<1%) patients thought their intervention was inapprop...

Evidence indicates that attentive eating is likely to influence food intake, and incorporation of attentive-eating principles into interventions provides a novel approach to aid weight loss and maintenance without the need for conscious calorie counting.

After acidic organelles induce signaling to activate ER calcium ion release, local microdomains of high calcium at ER–acidic organelle junctions feed back to activate further acidic organelle calcium release.