Background and aims: Ghrelin is an orexigenic 28-amino acid peptide produced by the stomach. Circulating ghrelin levels rise shortly before and fall shortly after every meal. Peptide YY (PYY), an anorexigenic 36-amino acid peptide, is secreted primarily from the intestinal mucosa of the ileum and large intestine. Plasma PYY levels begin to rise within 15 min after starting to eat and plateau within w90 min, remaining elevated for up to 6 h. Recently, some studies have tried to evaluate the potential role of ghrelin and PYY in the hyperphagia of patients with Prader-Willi syndrome (PWS). While hyperghrelinemia is well characterized in PWS, conflicting results have been reported for PYY. The aim of the study was to investigate ghrelin and PYY responses to a standard liquid high-fat meal in children with PWS. Patients and methods: Circulating levels of total ghrelin and PYY levels were assayed by RIA after overnight fasting and 45, 60, 90, and 180 min following a standard meal (Ensure 6 ml/kg) in 16 patients with PWS (11 boys and five girls, aged 4.6-10.7 years, including ten receiving 0.02 mg/kg per day rhGH for 2-18 months; body mass index (BMI) z-score: 0.6G0.2 and 1.6G0.5 for children treated or not treated with rhGH respectively), ten obese (eight boys and two girls, aged 9.2-15.6 years; BMI z-score: 2.4G0.2, i.e. BMI O97th centile for chronological age and sex) subjects, and 16 normalweight controls (five boys and 11 girls, aged 5.8-17.3 years; BMI z-score: 0.6G0.2). Results: PWS children showed higher fasting levels of ghrelin than obese and lean controls. Postprandial ghrelin drop was more pronounced in PWS than in the other study groups. No significant difference on fasting levels of PYY was found among groups. PWS showed a higher postprandial PYY rise than obese and lean controls. PWS patients treated and not treated with GH showed similar fasting and postprandial levels of ghrelin and PYY. Fasting PYY levels correlated negatively (P!0.05; rZK0.68) with those of ghrelin only in PWS. Conclusions: The results of this study confirm fasting hyperghrelinemia in PWS. Since in PWS adults an impaired postprandial suppression of plasma ghrelin was previously reported to be associated with a blunted postprandial PYY response, the finding of a meal-induced decrease and increase in ghrelin and PYY levels respectively in PWS children would imply that the regulation of appetite/satiety of these peptides is operative during childhood, and it progressively deteriorates and vanishes in adulthood when hyperphagia and obesity worsen.

We have evaluated the plasma GH response to a single injection of 1 microgram/kg of GH-releasing hormone (GHRH)-40 in 15 obese children and 15 age-matched control children. Most of the obese children showed a subnormal plasma GH response to GHRH and the mean plasma GH integrated area (IC-GH) following stimulation was significantly smaller in obese than control children. Plasma somatomedin-C (SM-C) levels were significantly higher in obese than control children, and were negatively correlated with the peak plasma GH levels (r = -0.616, P less than 0.01) and the IC-GH (r = -0.554, P less than 0.02) after GHRH. Non-esterified fatty acids (NEFA) and fasting plasma insulin levels were also elevated in obese children, but did not correlate with the extent of plasma GH response to GHRH. These data confirm previous observations on the refractoriness of obese children to release GH after GHRH, and imply that it may be due to the feedback inhibition operated by the elevated plasma levels of SM-C.

Study objectivesThe marginalisation of undocumented migrants raises concerns about equitable access to COVID-19 vaccination. This study aims to describe migrants’ hesitancy about the COVID-19 vaccination during the early phase of the vaccination campaign.SettingThis multicentric cross-sectional survey was conducted in health facilities providing care to undocumented migrants in the USA, Switzerland, Italy and France in February–May 2021.ParticipantsEligibility criteria included age >16 years, being of foreign origin and living without valid residency permit in the country of recruitment. A convenience sample of minimum 100 patients per study site was targeted.Primary and secondary outcome measuresData were collected using an anonymous structured questionnaire. The main outcomes were perceived access to the local COVID-19 vaccination programme and demand for vaccination.ResultsAltogether, 812 undocumented migrants participated (54.3% Geneva, 17.5% Baltimore, 15.5% Milano and 12.7% Paris). Most (60.9%) were women. The median age was 39 years (interquartile range 1). Participants originated from the Americas (55.9%), Africa (12.7%), Western Pacific (11.2%) Eastern Mediterranean (7.9%), Europe (7.6%) and South-East Asia (4.7%). Overall, 14.1% and 26.2% of participants, respectively, reported prior COVID-19 infection and fear of developing severe COVID-19 infection. Risk factors for severe infection were frequently reported (29.5%). Self-perceived accessibility of COVID-19 vaccination was high (86.4%), yet demand was low (41.1%) correlating with age, comorbidity and views on vaccination which were better for vaccination in general (77.3%) than vaccination against COVID-19 (56.5%). Participants mainly searched for information about vaccination in the traditional and social media.ConclusionsWe found a mismatch between perceived accessibility and demand for the COVID-19 vaccination. Public health interventions using different communication modes should build on trust about vaccination in general to tackle undocumented migrants’ hesitancy for COVID-19 vaccination with a specific attention to men, younger migrants and those at low clinical risk of severe infection.

Background. Exercise is recognized to evoke multisystemic adaptations that, particularly in obese subjects, reduce body weight, improve gluco-metabolic control, counteract sarcopenia and lower the risk of cardiometabolic diseases. Understanding the molecular and cellular mechanisms of exercise-induced benefits is of great interest due to the therapeutic implications against obesity.Objectives and methods. The aim of the present study was to evaluate time-related changes in size distribution and cell origin of extracellular vesicles (EVs) in obese and normal-weight subjects who underwent a moderate-intensity exercise on a treadmill (at 60% of their VO2max). Blood samples were drawn before, immediately at the end of the exercise and during the post-exercise recovery period (3h and 24h). Circulating EVs were analyzed by a nanoparticle tracking analysis and flow cytometry after labeling with the following cellspecific markers: CD14 (monocyte/macrophage), CD61 (platelet), CD62E (activated endothelium), CD105 (total endothelium), SCGA (skeletal muscle) and FABP (adipose tissue).Results. In all subjects, acute exercise reduced the release of total (i.e., 30-700 nm) EVs in circulation, predominantly EVs in the microvesicle size range (i.e., 130-700 nm EVs). The post-exercise release of microvesicles was higher in normal-weight than obese subjects; after exercise, circulating levels of exosomes (i.e., 30-130 nm EVs) and microvesicles were, respectively, lower and higher in females than males. In all experimental subgroups (males vs. females and obese vs. normal-weight subjects), acute exercise reduced and increased, respectively, CD61+ and SCGA+ EVs, being the effect on CD61+ EVs prolonged up to 24h after the end of the test with subjects in resting conditions. Total EVs, exosomes and CD61+ EVs were associated with HOMA-IR.Conclusions. Though preliminary, the results of the present study show that a single bout of acute exercise modulates the release of EVs in circulation, which are tissue-, sex-and BMI specific, suggesting that the exercise-related benefits might depend upon a complex interaction of tissue, endocrine, and metabolic factors.

BackgroundHedonic hunger refers to consumption of food just for pleasure and not to maintain energy homeostasis. Recently, consumption of food for pleasure was reported to be associated with increased circulating levels of both the orexigenic peptide ghrelin and the endocannabinoid 2-arachidonoyl-glycerol (2-AG) in normal-weight subjects. To date, the effects of hedonic hunger, and in particular of chocolate craving, on these mediators in obese subjects are still unknown.MethodsTo explore the role of some gastrointestinal orexigenic and anorexigenic peptides and endocannabinoids (and some related congeners) in chocolate consumption, we measured changes in circulating levels of ghrelin, glucagon-like peptide 1 (GLP-1), peptide YY (PYY), anandamide (AEA), 2-AG, palmitoylethanolamide (PEA), and oleoylethanolamide (OEA) in 10 satiated severely obese subjects after consumption of chocolate and, on a separate day, of a non-palatable isocaloric food with the same bromatologic composition. Evaluation of hunger and satiety was also performed by visual analogic scale.ResultsThe anticipatory phase and the consumption of food for pleasure were associated with increased circulating levels of ghrelin, AEA, 2-AG, and OEA. In contrast, the levels of GLP-1, PYY, and PEA did not differ before and after the exposure/ingestion of either chocolate or non-palatable foods. Hunger and satiety were higher and lower, respectively, in the hedonic session than in the non-palatable one.ConclusionsWhen motivation to eat is generated by exposure to, and consumption of, chocolate a peripheral activation of specific endogenous rewarding chemical signals, including ghrelin, AEA, and 2-AG, is observed in obese subjects. Although preliminary, these findings predict the effectiveness of ghrelin and endocannabinoid antagonists in the treatment of obesity.

No abstract

Metabolic syndrome is a combination of cardiometabolic risk factors, frequently detected in obese children and adolescents. To date, few clinical studies have evaluated the effectiveness of multidisciplinary body weight reduction programs on body mass index, body composition, muscle performance and fatigue in pediatric obese subjects suffering from metabolic syndrome, which might represent a sub-population that is more difficult to be treated and worthy of more intensive interventions than a population less metabolically complicated. The aim of the present study was to compare the impact of a three-week in-hospital multidisciplinary integrated body weight reduction program (BWRP) on body mass index (BMI), body composition (particularly, fat mass (FM) and fat-free mass (FFM)), motor control (evaluated by one-leg standing balance (OLSB) test), muscle performance (evaluated by the stair climbing test (SCT)) and fatigue (evaluated by fatigue severity scale (FSS)) in a pediatric obese population with or without metabolic syndrome. A pediatric population of 548 obese subjects without metabolic syndrome (F/M = 312/236; age range: 8–18 years; BMI: 36.3 ± 6.7 kg/m2) and 96 obese subjects with metabolic syndrome (F/M = 53/43; age range: 9–18 years; BMI: 38.3 ± 6.9 kg/m2) was recruited. The BWRP significantly reduced BMI, FM (expressed as %), SCT time and FSS score, and increased OLSB time in all subgroups of obese subjects, independent of sex and metabolic syndrome, with preservation of FFM. No significant differences in |ΔBMI|, |ΔFM|, |ΔOLSB| or |ΔSCT| times and |ΔFSS| score were found when comparing subjects (males and females) with or without metabolic syndrome, apart from obese females without metabolic syndrome, who exhibited a lower weight loss and FM (expressed as %) reduction when compared to the corresponding male counterpart. In conclusion, the beneficial effects of a three-week BWRP on BMI, body composition, muscle performance and fatigue in a pediatric obese population were not found to be different in patients with or without metabolic syndrome, thus indicating that the more metabolically compromised patient is as responsive to a short-term BWRP as the patient without metabolic syndrome. More prolonged follow-up studies are, however, necessary in order to verify whether the adherence to the multidisciplinary recommendations at home and the long-term maintenance of the positive effects in the two subgroups of patients will remain similar or not.

No abstract