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Breakfast Skipping, Weight, Cardiometabolic Risk, and Nutrition Quality in Children and Adolescents: A Systematic Review of Randomized Controlled and Intervention Longitudinal Trials.
Ricotti, R, Caputo, M, Monzani, A, Pigni, S, Antoniotti, V, Bellone, S, Prodam, F
Nutrients. 2021;(10)
Abstract
Breakfast skipping increases with age, and an association with a high risk of being overweight (OW) and of obesity (OB), cardiometabolic risk, and unhealthy diet regimen has been demonstrated in observational studies with children and adults. Short-term intervention trials in adults reported conflicting results. The purpose of this systematic review was to summarize the association of breakfast skipping with body weight, metabolic features, and nutrition quality in the groups of young people that underwent randomized controlled (RCT) or intervention longitudinal trials lasting more than two months. We searched relevant databases (2000-2021) and identified 584 articles, of which 16 were suitable for inclusion. Overall, 50,066 children and adolescents were included. No studies analyzed cardiometabolic features. Interventions were efficacious in reducing breakfast skipping prevalence when multi-level approaches were used. Two longitudinal studies reported a high prevalence of OW/OB in breakfast skippers, whereas RCTs had negligible effects. Ten studies reported a lower-quality dietary intake in breakfast skippers. This review provides insight into the fact that breakfast skipping is a modifiable marker of the risk of OW/OB and unhealthy nutritional habits in children and adolescents. Further long-term multi-level intervention studies are needed to investigate the relationship between breakfast, nutrition quality, chronotypes, and cardiometabolic risk in youths.
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Supplementation with Bifidobacterium breve BR03 and B632 strains improved insulin sensitivity in children and adolescents with obesity in a cross-over, randomized double-blind placebo-controlled trial.
Solito, A, Bozzi Cionci, N, Calgaro, M, Caputo, M, Vannini, L, Hasballa, I, Archero, F, Giglione, E, Ricotti, R, Walker, GE, et al
Clinical nutrition (Edinburgh, Scotland). 2021;(7):4585-4594
Abstract
BACKGROUND & AIMS Variations in gut microbiota might impact metabolism leading to body weight excess. We assessed the impact of a probiotic supplementation in pediatric obesity on weight, metabolic alterations, selected gut microbial groups, and functionality. METHODS Cross-over, double-blind, randomized control trial (BIFI-OBESE trial; NCT03261466). 101 youths (6-18 years, Tanner stage ≥2) with obesity and insulin-resistance on diet were randomized to 2 × 109 CFU/AFU/day of Bifidobacterium breve BR03 (DSM 16604) and B. breve B632 (DSM 24706) (51) or placebo (50) for 8 weeks with a 4-weeks wash-out period. RESULTS All subjects (M/F 54/47) completed the first 8 weeks, and 82 (M/F 43/39) the last part without adverse events. Mixed-effects models revealed a carry-over effect on many variables in the entire study, narrowing the analysis to the first 8 weeks before the wash-out periods. All subjects improved metabolic parameters, and decreased weight and Escherichia coli counts. Probiotics improved insulin sensitivity at fasting (QUICKI, 0.013 CI95%0.0-0.03) and during OGTT (ISI, 0.654 CI95%-0.11-1.41). Cytokines, GLP1, and target microbial counts did not vary. Of 25 SCFAs, acetic acid and acetic acid pentyl-ester relative abundance remained stable in the probiotics, while increased in the placebo (p < 0.02). A signature of five butanoic esters identified three clusters, one of them had better glucose responses during probiotics. CONCLUSION An 8 weeks treatment with B. breve BR03 and B632 had beneficial effects on insulin sensitivity in youths with obesity. Microbiota functionality could influence metabolic answers to probiotics. Long-term studies to confirm and enrich our findings are justified. Tailored probiotic treatments could be an additional strategy for obesity. TRIAL REGISTRATION NCT03261466.
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Preclinical Activity of Sacituzumab Govitecan, an Antibody-Drug Conjugate Targeting Trophoblast Cell-Surface Antigen 2 (Trop-2) Linked to the Active Metabolite of Irinotecan (SN-38), in Ovarian Cancer.
Perrone, E, Lopez, S, Zeybek, B, Bellone, S, Bonazzoli, E, Pelligra, S, Zammataro, L, Manzano, A, Manara, P, Bianchi, A, et al
Frontiers in oncology. 2020;:118
Abstract
Background: Epithelial ovarian cancer (EOC) is the most lethal gynecologic malignancy. Sacituzumab govitecan (SG) is a novel antibody-drug-conjugate (ADC) targeting trophoblast-antigen-2 (Trop-2), a cell surface glycoprotein highly expressed in many epithelial tumors, to deliver SN-38, the active metabolite of irinotecan. This study aimed to evaluate Trop-2 expression in EOC tissues and the preclinical activity of SG against primary EOC cell lines and xenografts. Methods: Trop-2 expression was assessed in 90 formalin-fixed-paraffin-embedded tumors and nine primary tumor cell lines by immunohistochemistry (IHC) and flow cytometry, respectively. Trop-2 expression and cell viability after exposure to SG in primary tumor cell lines, non-targeting control ADC, and SG-parental antibody hRS7 were evaluated using flow-cytometry-based-assays. Antibody-dependent-cell-cytotoxicity (ADCC) against Trop-2+ and Trop-2- EOC cell lines was tested in vitro using 4 h Chromium-release-assays. In vivo activity of SG was evaluated against Trop-2+ EOC xenografts. Results: Moderate-to-strong staining was seen in 47% (42/90) of ovarian tumors by IHC while 89% (8/9) of the primary EOC cell lines overexpressed Trop-2 by flow cytometry. EOC Trop-2+ were significantly more sensitive to SG compared to control ADC (p < 0.05). Both SG and hRS7 mediated high ADCC activity against Trop-2+ cell lines. SG also induced significant bystander killing of Trop-2- tumor cells admixed with Trop-2+ EOC cells. In in vivo experiments SG treatment demonstrated impressive anti-tumor activity against chemotherapy-resistant EOC xenografts. Conclusion: SG demonstrates remarkable preclinical activity against biologically aggressive and chemotherapy-resistant EOC cell lines and a significant bystander effect against EOC cell lines with heterogenous Trop-2 expression. Clinical trials are warranted.
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A Systematic Review of the Association of Skipping Breakfast with Weight and Cardiometabolic Risk Factors in Children and Adolescents. What Should We Better Investigate in the Future?
Monzani, A, Ricotti, R, Caputo, M, Solito, A, Archero, F, Bellone, S, Prodam, F
Nutrients. 2019;11(2)
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Plain language summary
Childhood obesity is a major public health issue across the world. The incidence of skipping breakfast among children and adolescent is rising. Numerous studies have shown a positive relationship between skipping breakfast and overweight or obesity. The aim of the study was to analyse the association of skipping breakfast with body weight and metabolic outcomes in the paediatric population. The study is a systemic review focusing on studies published in the last ten years. 39 articles were included for analysis and data from a total of 286,804 children and adolescents were reported. The systemic review demonstrates that children and adolescents who skip breakfast are at higher risk to be or become overweight or obese. Authors conclude that skipping breakfast may be a potential marker of lifestyle behaviours in children and adolescents that promote overweight or obesity and metabolic diseases.
Abstract
The incidence of skipping breakfast in pediatric subjects is rising, and a relationship with overweight (OW) and obesity (OB) has been shown. Associations with cardiovascular outcomes and skipping breakfast in adults have been reported. The purpose of this systematic review was to summarize the association of skipping breakfast with body weight and metabolic outcomes in the pediatric population. We searched relevant databases (2008⁻2018) and identified 56 articles, of which 39 were suitable to be included, basing on inclusion criteria (observational; defined breakfast skipping; weight and/or metabolic outcomes). Overall, 286,804 children and adolescents living in 33 countries were included. The definitions of OW/OB, skipping breakfast, and the nutrient assessment were highly heterogeneous. Confounding factors were reported infrequently. The prevalence of skipping breakfast ranged 10⁻30%, with an increasing trend in adolescents, mainly in girls. Skipping breakfast was associated with OW/OB in the 94.7% of the subjects. The lack of association was shown mainly in infants. Moreover, 16,130 subjects were investigated for cardiometabolic outcomes. Skipping breakfast was associated with a worse lipid profile, blood pressure levels, insulin-resistance, and metabolic syndrome. Five studies reported a lower quality dietary intake in breakfast skippers. This review supports skipping breakfast as an easy marker of the risk of OW/OB and metabolic diseases, whether or not it is directly involved in causality. We encourage intervention studies using standardized and generalizable indicators. Data on confounders, time of fasting, chronotypes, and nutrition quality are needed to establish the best practice for using it as a tool for assessing obesity risk.
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Diagnosis, treatment and prevention of pediatric obesity: consensus position statement of the Italian Society for Pediatric Endocrinology and Diabetology and the Italian Society of Pediatrics.
Valerio, G, Maffeis, C, Saggese, G, Ambruzzi, MA, Balsamo, A, Bellone, S, Bergamini, M, Bernasconi, S, Bona, G, Calcaterra, V, et al
Italian journal of pediatrics. 2018;(1):88
Abstract
The Italian Consensus Position Statement on Diagnosis, Treatment and Prevention of Obesity in Children and Adolescents integrates and updates the previous guidelines to deliver an evidence based approach to the disease. The following areas were reviewed: (1) obesity definition and causes of secondary obesity; (2) physical and psychosocial comorbidities; (3) treatment and care settings; (4) prevention.The main novelties deriving from the Italian experience lie in the definition, screening of the cardiometabolic and hepatic risk factors and the endorsement of a staged approach to treatment. The evidence based efficacy of behavioral intervention versus pharmacological or surgical treatments is reported. Lastly, the prevention by promoting healthful diet, physical activity, sleep pattern, and environment is strongly recommended since the intrauterine phase.
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Effects of growth hormone (GH) therapy withdrawal on glucose metabolism in not confirmed GH deficient adolescents at final height.
Prodam, F, Savastio, S, Genoni, G, Babu, D, Giordano, M, Ricotti, R, Aimaretti, G, Bona, G, Bellone, S
PloS one. 2014;(1):e87157
Abstract
CONTEXT OBJECTIVE Growth hormone deficiency (GHD) is associated with insulin resistance and diabetes, in particular after treatment in children and adults with pre-existing metabolic risk factors. Our aims were. i) to evaluate the effect on glucose metabolism of rhGH treatment and withdrawal in not confirmed GHD adolescents at the achievement of adult height; ii) to investigate the impact of GH receptor gene genomic deletion of exon 3 (d3GHR). DESIGN SETTING We performed a longitudinal study (1 year) in a tertiary care center. METHODS 23 GHD adolescent were followed in the last year of rhGH treatment (T0), 6 (T6) and 12 (T12) months after rhGH withdrawal with fasting and post-OGTT evaluations. 40 healthy adolescents were used as controls. HOMA-IR, HOMA%β, insulinogenic (INS) and disposition (DI) indexes were calculated. GHR genotypes were determined by multiplex PCR. RESULTS In the group as a whole, fasting insulin (p<0.05), HOMA-IR (p<0.05), insulin and glucose levels during OGTT (p<0.01) progressively decreased from T0 to T12 becoming similar to controls. During rhGH, a compensatory insulin secretion with a stable DI was recorded, and, then, HOMAβ and INS decreased at T6 and T12 (p<0.05). By evaluating the GHR genotype, nDel GHD showed a decrease from T0 to T12 in HOMA-IR, HOMAβ, INS (p<0.05) and DI. Del GHD showed a gradual increase in DI (p<0.05) and INS with a stable HOMA-IR and higher HDL-cholesterol (p<0.01). CONCLUSIONS In not confirmed GHD adolescents the fasting deterioration in glucose homeostasis during rhGH is efficaciously coupled with a compensatory insulin secretion and activity at OGTT. The presence of at least one d3GHR allele is associated with lower glucose levels and higher HOMA-β and DI after rhGH withdrawal. Screening for the d3GHR in the pediatric age may help physicians to follow and phenotype GHD patients also by a metabolic point of view.
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Effect of Arginine Infusion on Ghrelin Secretion in Growth Hormone Sufficient and GH Deficient Children.
Prodam, F, Genoni, G, Bellone, S, Longhi, S, Agarla, V, Bona, G, Radetti, G
International journal of endocrinology and metabolism. 2012;(2):470-4
Abstract
BACKGROUND The physiological link between ghrelin and growth hormone (GH) has not yet been fully clarified. Furthermore, the existence of a negative feedback mechanism between growth hormone-insulin-like growth factor (GH-IGF)-I axis and ghrelin and the influence of amino acids on ghrelin secretion in children remain matters of debate. OBJECTIVES To understand the regulation of ghrelin secretion and clarify the relationship between ghrelin and GH secretion in GH-deficient (GHD) and GH-sufficient (GHS) children. PATIENTS AND METHODS Ten GHD (male/female [M/F], 6/4; age [mean ± SEM], 10.7 ± 0.9 years) and 10 GHS prepubertal children (M/F, 6/4; age [mean ± SEM], 10.3 ± 0.6 years), underwent an arginine (ARG) test (infusion, 0.5 g/kg, iv). Levels of GH, total ghrelin, and acylated ghrelin (AG) were assayed every 30 min from 0 to +120 min. RESULTS Peak GH values were lower in GHD subjects than in GHS subjects (P < 0.0001). The baseline levels, peak levels, or area under the curves (AUC) for total ghrelin and AG were similar between GHD and GHS children. ARG infusion was followed by a slight to significant decrease in total ghrelin levels, but not AG levels, both in GHD and GHS subjects with a nadir at +30 min. No correlation was seen between GH, total ghrelin, or AG response and ARG infusion. CONCLUSIONS Total ghrelin and AG levels seemed unaffected by GH status in prepubertal children. ARG infusion was unable to blunt ghrelin secretion irrespective of GH status in childhood. Moreover, since ARG influences GH secretion via modulation of somatostatin release, ghrelin secretion seems to be partially refractory to somatostatin action.
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A novel CD4 T-cell epitope described from one of the cervical cancer patients vaccinated with HPV 16 or 18 E7-pulsed dendritic cells.
Wang, X, Santin, AD, Bellone, S, Gupta, S, Nakagawa, M
Cancer immunology, immunotherapy : CII. 2009;(2):301-8
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Abstract
Previously, safety and immunogenicity of human papillomavirus type 16 (HPV16) or 18 E7-pulsed dendritic cells (DC) vaccinations were demonstrated in a dose-escalation Phase I clinical trial which enrolled ten patients diagnosed with stage IB or IIA cervical cancer (nine HPV 16-positive, one HPV 18-positive). The goal of the study was to define the T-cell epitopes of HPV 16 or 18 E7 protein in these patients in order to develop new strategies for treating HPV-associated malignancies. This was accomplished through establishing T-cell lines by stimulating peripheral blood mononuclear cells with autologous mature DC pulsed with the HPV 16 or 18 E7 protein, examining the T-cell responses using ELISPOT assays, and isolating E7-specific T-cell clones based on IFN-gamma secretion. Then, the epitope was characterized in terms of its core sequence and the restriction element. Twelve T-cell lines from eight subjects (seven HPV 16-positive, one HPV 18-positive) were evaluated. Positive T-cell responses were demonstrated in four subjects (all HPV 16-positive). All four were positive for the HPV 16 E7 46-70 (EPDRAHYNIVTFCCKCDSTLRLCVQ) region. T-cell clones specific for the E7 47-70 region were isolated from one of the subjects. Further analyses revealed a novel, naturally processed, CD4 T-cell epitope, E7 58-68 (CCKCDSTLRLC), restricted by the HLA-DR17 molecule.