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Metabolic disease is rising along with both global industrialization and the use of new commercial, agricultural, and industrial chemicals and food additives. Exposure to these compounds may contribute to aspects of metabolic disease such as obesity, diabetes, and fatty liver disease. Ingesting compounds in the food supply is a key route of human exposure, resulting in the interaction between toxicants or additives and the intestinal microbiota. Toxicants can influence the composition and function of the gut microbiota, and these microbes can metabolize and transform toxicants and food additives. Microbe-toxicant interactions in the intestine can alter host mucosal barrier function, immunity, and metabolism, which may contribute to the risk or severity of metabolic disease development. Targeting the connection between toxicants, food, and immunity in the gut using strategies such as fermentable fiber (i.e., inulin) may mitigate some of the effects of these compounds on host metabolism. Understanding causative factors in the microbe-host relationship that promote toxicant-induced dysmetabolism is an important goal. This review highlights the role of common toxicants (i.e. persistent organic pollutants, pesticides, and fungicides) and food additives (emulsifiers and artificial sweeteners) found in our food supply that alter the gut microbiota and promote metabolic disease development.

With the rise in fast-food culture and the continued high numbers of tobacco-related deaths, there has been a great deal of interest in understanding the relationship between high-fat diet (HFD) and nicotine use behaviors. Using adult mice and a patch-clamp electrophysiology assay, we investigated the influence of HFD on the excitability of ventral tegmental area (VTA) dopamine neurons and pyramidal neurons in the medial prefrontal cortex (mPFC) given their role in modulating the reinforcing effects of nicotine and natural rewards. We then examined whether HFD-induced changes in peripheral markers were associated with nicotine use behaviors. Here, mice were assigned standard diet (SD) or HFD for 6 weeks and then trained to self-administer nicotine using an e-vape® self-administration (EVSA) assay. After the last session, changes in glucose, insulin, and leptin were assessed with ELISA. HFD-assigned mice displayed a decrease in intrinsic excitability of VTA dopamine neurons; but an increase in intrinsic excitability of layer VI prelimbic mPFC neurons. SD-assigned female mice demonstrated enhanced nicotine EVSA during fixed-ratio 3 relative to SD males. HFD-assigned male and female mice displayed increased nicotine EVSA during FR1. However, only HFD-assigned male mice exhibited enhanced nicotine EVSA during FR3. Finally, HFD-assigned male and female mice displayed increased leptin levels. However, we only observed a direct correlation between leptin levels and EVSA responding during FR1 in HFD-fed male mice. These results suggest that high-fat diet alter nicotine intake in a sex-specific manner, and this may be due to diet-induced changes in neuronal excitability and circulating leptin levels., (Copyright © 2025. Published by Elsevier Inc.)

Objective: Conduct a systematic review and meta-analysis of randomized controlled trials (RCTs) of behavioural and psychological interventions for managing paediatric obesity., Methods: Eligible studies, published between 1985 and 2022, included 0 to 18 year olds with outcomes reported ≥3 months post-baseline, including patient-reported outcome measures (PROMs), cardiometabolic and anthropometric outcomes, and adverse events (AEs). We pooled data using a random effects model and assessed certainty of evidence (CoE) related to minimally important difference estimates for outcomes using GRADE., Results: We included 73 unique RCTs (n = 6305 participants, 53% female). Intervention types included physical activity (n = 1437), nutrition (n = 447), psychological (n = 1336), technology-based (n = 901) or multicomponent (≥2 intervention types, n = 2184). Physical activity had a small effect on health-related quality of life (HRQoL), varying effects ranging from moderate to very large on blood pressure, lipids and insulin resistance, and a small effect on BMIz. Nutrition had a small effect on lipids, insulin resistance and BMIz. Psychological interventions showed a small effect on HRQoL and triglycerides and moderate benefits on depressive symptoms, while technology interventions showed small benefits on blood pressure and BMIz. Multicomponent interventions had a large benefit on anxiety, small benefit on depressive symptoms, with large to very large benefits on lipids, and small benefits for diastolic blood pressure, insulin resistance and BMIz. AEs were reported infrequently, and when reported, were described as mild., Conclusion: Physical activity and multicomponent interventions showed improvements in PROMs, cardiometabolic and anthropometric outcomes. Future trials should consistently measure PROMs, evaluate outcomes beyond the intervention period, and study children <6 years of age., (© 2025 The Author(s). Pediatric Obesity published by John Wiley & Sons Ltd on behalf of World Obesity Federation.)

Competing Interests: Declaration of interests FR declares research grants from Ethicon (Johnson & Johnson), Novo Nordisk, and Medtronic; consulting fees from Morphic Medical; speaking honoraria from Medtronic, Ethicon, Novo Nordisk, Eli Lilly, and Amgen; has served (unpaid) as a member of the scientific advisory board for Keyron, and a member of data safety and monitoring board for GI Metabolic Solutions; is president of the Metabolic Health Institute (non-profit); and is sole director of Metabolic Health International and London Metabolic and Bariatric Surgery (private practice). JRLF declares personal consulting or speaker fees from Novo Nordisk, IFA Celtics, Eli Lilly, and Merck. PS declares research grants (paid to institution) from the National Health and Medical Research Council; coauthorship of manuscripts with medical writing assistance from Novo Nordisk and Eli Lilly; and an unpaid position in the leadership group of the Obesity Collective. WAB declares research grants from Johnson & Johnson, Medtronic, Gore, Applied Medical, Novo Nordisk, National Health and Medical Research Council, Myerton, and the Australian Commonwealth Government; and personal consulting fees for lectures and advisory boards from Johnson & Johnson, Gore, Novo Nordisk, Pfizer, Medtronic, Eli Lily, and Merck Sharp & Dohme. GM declares consulting fees from Novo Nordisk, Boehringer Ingelheim, Eli Lilly, Medtronic, Fractyl, and Recor; and is a scientific advisor for Keyron, Metadeq, GHP Scientific, and Jemyll. MB declares personal honoraria as a consultant and speaker from Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Daiichi Sankyo, Eli Lilly, Novo Nordisk, Novartis, Pfizer, and Sanofi. ML declares personal consulting fees from, and has served on scientific boards for, Novo Nordisk, Pfizer, and Eli Lilly. LMSC declares consultancy fees from Antaros Medical. MTvdM declares past consulting fees from Netcare PTY and Novo Nordisk. RVC declares research grants from Johnson & Johnson and Medtronic; honoraria for lectures and presentations from Johnson & Johnson, Medtronic, and Novo Nordisk; and serving on scientific advisory boards for Morphic Medical, Johnson & Johnson, and Medtronic. AM declares research grants from USV (India) and AstraZeneca; honoraria for lectures from USV (India), Eli Lilly, Lupin, Boehringer Ingelheim, Janssen, Cipla, AstraZeneca, Glenmark, Zydus, Novo Nordisk, Sanofi, Danone, Abbott, and the Almond Board of California; support for attending meetings or travel from USV (India), Eli Lilly, Boehringer Ingelheim, AstraZeneca, Lupin, and the Almond Board of California. KC is a primary investigator for Rhythm Pharmaceuticals, Bioprojects, and Integrative Phenomic (SME) trials; declares support for attending meetings or travel from Rhythm Pharmaceuticals and Novo Nordisk; and received research grants or support from Rhythm Pharmaceuticals to conduct research or deliver lectures via Institutions (Assistance Publique-Hôpitaux de Paris, Sorbonne Université). RFK declares consulting fees from Novo Nordisk, Weight Watchers, Eli Lilly, Boehringer Ingelheim, Altimmune, Structure, and Regeneron. JN has no personal relationships with industry; is an employee of the Obesity Action Coalition, which receives unrestricted support from a wide variety of companies and organisations interested in obesity care including, from the pharmaceutical industry (NovoNordisk, Eli Lilly, Boehringer Ingelheim, Pfizer, Amgen, Genentech, Regeneron, Wave Life Sciences, Zealand Pharma, KVKTech, Madrigal Pharmaceuticals, Structure Therapeutics, Biohaen Pharmaceuticals, and Currax), surgical industry (Intuitive, Ethicon, Medtronic, and Boston Scientific), behavioural care (WW International and WondrHealth), and not-for-profit medical societies (American Society for Metabolic and Bariatric Surgery, the Obesity Society, and the Obesity Medicine Association); and is president and chief executive officer for the Obesity Action Coalition. NS declares consulting or speaker honoraria from Abbott, Amgen, AstraZeneca, Boehringer Ingelheim, Eli Lilly, Hanmi Pharmaceuticals, Janssen, Merck Sharp & Dohme, Novartis, Novo Nordisk, Pfizer, Roche Diagnostics, and Sanofi; and grants (paid to institution) from AstraZeneca, Boehringer Ingelheim, Novartis, and Roche Diagnostics. WTG declares consulting fees as a member of advisory boards for Boehringer Ingelheim, Eli Lilly, Novo Nordisk, Pfizer, Fractyl Health, Alnylam Pharmaceuticals, Inogen, Zealand Pharma, Allurion, Carmot Therapeutics (Roche), Regeneron, and Merck; research grants as a site principal investigator for multicentre clinical trials sponsored by his university and funded by Novo Nordisk, Eli Lilly, Epitomee, Neurovalens, and Pfizer; has served as a consultant on an advisory board for the non-profit Milken Foundation; and is a member of the data monitoring committee for phase 3 clinical trials conducted by Boehringer Ingelheim and Eli Lilly. BL declares research grants from US National Institutes of Health (not related to this Commission); and personal consulting fees from UpToDate. RHE declares consulting fees from Novo Nordisk, The Healthy Aging Co, and WW International. AK declares research grants from Novo Nordisk, ELPEN Pharma, and Pharmaserve–Lilly; serving on scientific advisory boards for Novo Nordisk, Pharmaserve–Lilly, Sanofi, and Boehringher Ingelheim; and honoraria for lectures by Novo Nordisk, Pharmaserve–Lilly, AstraZeneca, MSD, Sanofi, Bausch Health, Ethicon, Galenica Pharma, Epsilon Health, and Winmedica. J-PD declares grants from the Canadian Institutes of Health Research; and personal consulting fees from INVERSAGO Pharma as a member of the advisory board. KWT declares speaker honoraria or consulting fees from Novo Nordisk, Eurodrug Laboratories, iNova Pharmaceuticals, and DKSH; travel support from Novo Nordisk; and serving on advisory boards of Novo Nordisk, DKSH (representing Eli Lilly), Abbott Nutrition, and Boehringer Ingelheim. ER declares research grants from Eli Lilly and Novo Nordisk; and consulting fees from Energesis Pharmaceuticals, Eli Lilly, Amway, Kintai Therapeutics, YSOPIA Bioscience (previously LNC Therapeutics), CINFINA Pharmaceuticals, and Boehringer Ingelheim. JBD declares personal consulting fees from Reshape Lifescience, and Nestle Health Science Australia; serving on advisory boards and speaker panels for Reshape Lifescience, Nestle Health Science Australia, Novo Nordisk, Eli Lilly, and I-nova; and speaker fees from HealthED and Eurodrug Laboratories. FP declares personal consulting fees from Medtronic, Ethicon, Novo Nordisk, and Eli Lilly. DEC declares serving on scientific advisory boards for GI Dynamics, Gila Therapeutics, and Endogenex. TK declares research grants from Nippon Boehringer Ingelheim and Sumitomo Pharma; consulting fees from Taisho Pharmaceutical, Eli Lilly Japan, and Novo Nordisk; and honoraria for lectures from Nippon Boehringer Ingelheim, Sumitomo Pharma, Teijin Pharma, MSD, Eli Lilly Japan, Mitsubishi Tanabe Pharma Corporation, Taisho Pharmaceutical, and Novo Nordisk. NBAB declares research grants from NovoNordisk and AstraZeneca; and honoraria for lectures and presentations from Novo Nordisk, Boehringer Ingelheim, AstraZeneca, Merck, MSD, Sanofi, and Servier. JV was national clinical director for diabetes and obesity at NHS England from April, 2013, to September, 2023; declares funding support from the North West London National Institute for Health and Care Research Applied Research Collaboration, CW+ (the official charity of Chelsea and Westminster Hospital NHS Foundation Trust), European Commission Horizon Europe 2022, and UK Research and Innovation Horizon Europe. CWlR declares grants from the Irish Research Council, Science Foundation Ireland, Anabio, and the Health Research Board; serving on advisory boards and speakers panels for Novo Nordisk, Herbalife, GI Dynamics, Eli Lilly, Johnson & Johnson, Glia, Irish Life Health, Boehringer Ingelheim, Currax, Zealand Pharma, Keyron, and Rhythm Pharmaceuticals; was the chief medical officer and director (unpaid) of the Medical Device Division of Keyron in 2021; was a previous investor in Keyron, which develops endoscopically implantable medical devices intended to mimic the surgical procedures of sleeve gastrectomy and gastric bypass (no patients have been included in any of Keyron's studies and they are not listed on the stock market); was gifted stock holdings in September, 2021, and divested all stock holdings in Keyron in September, 2021; continues to provide scientific advice (unpaid) to Keyron; and provides (unpaid) obesity clinical care in the Beyond BMI clinic (Dublin, Ireland), and is a shareholder in the clinic. NJF-L declares personal consulting fees from WHO and the European Commission (Best Re-MaP joint action [a project aimed to develop and implement policy proposals in nutrition for children]). NFA declares personal consulting fees from Ethicon and Eli Lilly; and serving on scientific advisory boards for Novo Nordisk and Eli Lilly. ISF declares personal consulting fees from Rhythm Pharmaceuticals, Eli Lilly, Novo Nordisk, SV Health, Nodthera Therapeutics, and Goldman Sachs. VMM declares personal consulting fees from Boehringer Ingelheim and Novo Nordisk. JPK declares research grants from the US National Institutes of Health (grants U54, U01, and U54 GM104940 that could be indirectly linked to the work of this Commission); and honoraria for serving on scientific advisory boards of Novo Nordisk and the Annual Reviews of Nutrition. KMM reports serving on scientific advisory boards for Novo Nordisk and Rhythm Pharmaceuticals; and is a member of a drug safety and monitoring board for Novartis. PRS declares research grants from Ethicon and Medtronic; personal consulting fees or honoraria from GI Dynamics, Keyron, Persona, Mediflix, Metabolic Health International, Eli Lilly, Heron, Novo Nordisk, and Klens; serving on scientific advisory boards for SE Healthcare Board of Directors, GI Dynamics, Keyron, Persona, and Mediflix; and has ownership interest in SE Healthcare, Mediflix, and Metabolic Health International. HT declares research grants from Amgen, Boehringer Ingelheim, Daiichi Sankyo, Novartis, and Novo Nordisk; serving on advisory boards for Novo Nordisk, Daiichi Sankyo, and Novartis; and speakers fees from Daiichi Sankyo, Novartis, and Novo Nordisk. MHT declares participation in a scientific advisory board meeting of ERX Pharmaceuticals (Cambridge, MA, USA) in 2019; was a member of the Research Cluster Advisory Panel of the Novo Nordisk Foundation between 2017 and 2019; funding for research projects from Novo Nordisk (2016–20) and Sanofi-Aventis (2012–19); consulted twice for Boehringer Ingelheim (2020 and 2021); delivered scientific lectures for Sanofi-Aventis (2020), Boehringer Ingelheim (2024), and AstraZeneca (2024); is cofounder of the biotech startups Ghrelco and Bluewater Biotech (2024); is chief executive officer and chief scientific officer of Helmholtz Munich, and is co-responsible for countless collaborations of the employees with a multitude of companies and institutions worldwide (in this capacity, discusses potential projects with and signs contracts for the centres institutes related to research collaborations worldwide, including, but not limited to, pharmaceutical corporations such as Boehringer Ingelheim, Novo Nordisk, Roche Diagnostics, Arbormed, Eli Lilly, and SCG Cell Therapy, and as chief scientific officer is responsible for commercial technology transfer activities); and is a former member of the scientific advisory board of ERX, which is developing the drug celastrol, but has no current competing interests. JPHW declares consultancy or advisory board work for the pharmaceutical industry contracted via the University of Liverpool (no personal payment) for Altimmune, Amgen, AstraZeneca, Boehringer Ingelheim, Eli Lilly, Napp, Novo Nordisk, Menarini, Pfizer, Regeneron, Rhythm Pharmaceuticals, Sanofi, Saniona, Tern, Shionogi, and YSOPIA Bioscience; research grants for clinical trials from AstraZeneca and Novo Nordisk; personal honoraria or lecture fees from AstraZeneca, Boehringer Ingelheim, Medscape, Napp, Novo Nordisk, and Rhythm Pharmaceuticals; is past president of the World Obesity Federation; and was national lead for the Metabolic and Endocrine Speciality Group of the National Institute of Health and Reasearch Clinical Research Network from 2010–24; and is a member of the Rank Prize Funds Nutrition Committee and a past member of the RCP committee on nutrition, weight, and health. FCS declares personal consulting fees from Eli Lilly, Novo Nordisk, Boehringer Ingelheim, Pfizer, Gelesis, Currax, and Rhythm Pharmaceuticals; and has served on scientific advisory boards for Eli Lilly and Novo Nordisk. LAB declares serving on scientific advisory board for Novo Nordisk (for the ACTION Teens study) and Eli Lilly; and speaker fees (paid to institution) from Novo Nordisk. LMK declares participation on advisory boards for Boehringer Ingelheim and Eli Lilly; and consulting fees from Altimmune, Amgen, AstraZeneca, Boehringer Ingelheim, Cytoki, Ethicon, Glyscend, Kallyope, Eli Lilly, Neurogastrx, Novo Nordisk, Optum Health, Perspectum, Pfizer, Sidekick Health, Xeno Biosciences, and Zealand Pharma. RLB declares research grants from the Sir Jules Thorn Trust, National Institutes for Health and Care Research, Rosetrees Trust, and Novo Nordisk; personal consulting fees from Eli Lilly, Novo Nordisk, Gila Therapeutics, Epitomee Medical, Medscape, ViiV, and International Medical Press; serving on scientific advisory boards for Eli Lilly, Novo Nordisk, Pfizer, ViiV, and International Medical Press; leadership or fiduciary roles (unpaid) in other board, society, committee, or advocacy groups for the Royal College of Physicians; is a committee member of the British Obesity and Metabolic Surgery Society and the National Bariatric Surgery Registry; is scientific chair of the International Federation for the Surgery of Obesity, European Chapter; is a trustee for the Association for the Study of Obesity and the Obesity Empowerment Network UK; is a member of the Obesity Guideline Update Committee for the National Institutes for Health and Care Excellence; and, since May 15, 2023, is senior vice president for Eli Lilly and holds shares in Eli Lilly, and as a result has had no active involvement in this Commission since May 1, 2023 (however, to comply with authorship requirements, RLB read and approved the final draft [see Acknowledgements for details]). RV declares research grants from Pfizer; fees for educational purposes from Novo Nordisk, AstraZeneca, and Eli Lilly; and serving on scientific advisory boards for Eli Lilly and Novo Nordisk. MO-G declares research grants from Adamed Poland; personal consulting fees from Baush Health, Novo Nordisk, and Promed Poland; and serving on scientific advisory boards for Baush Health, Novo Nordisk, and Boehringer Ingelheim. HJG declares consulting fees from Gila Pharmaceuticals and Pfizer. SL declares research grants from Merck Sharp & Dohme, Novo Nordisk, and LG Chem; and honoraria as a consultant or speaker for AstraZeneca, Boehringer Ingelheim, Abbott, LG Chem, Daewoong Pharmaceutical, Chong Kun Dang Pharmaceutical, and Novo Nordisk. All other authors have no competing interests.

Objectives: To examine individual, family, and program characteristics associated with changes in anthropometric and cardiometabolic health indicators in children with overweight or obesity after participating in multidisciplinary obesity management for 12 months., Methods: Participants included children 2-17 years old with overweight or obesity enrolled in the CANadian Pediatric Weight Management Registry (CANPWR). Multiple linear regression analyses were conducted to investigate the associations between individual, family, and program characteristics and changes in anthropometry (WHO BMI z-score) and cardiometabolic health indicators (systolic and diastolic blood pressure; fasting and 2-h glucose post-oral glucose tolerance test (OGTT); high density lipoprotein- (HDL) and non-HDL cholesterol and fasting triglycerides)., Results: BMI z-score data were available from 1065/1286 (82.8%) at 6-months post-baseline and 893/1286 (69.4%) at 12-months post-baseline. At 6-months, BMI z-score decreased relative to baseline (mean difference (MD) [95% confidence interval (CI)] = -0.08 [-0.10 to -0.06]; p < 0.001). BMI z-score (MD [95% CI] = -0.08 [-0.13 to -0.04); p = 0.001) and fasting triglycerides (MD [95% CI] = -0.07 [-0.13 to -0.02); p = 0.011) decreased at 12 months from baseline. Older age at baseline (estimated β = 0.025; 95% CI [0.006, 0.042], p = 0.007) and female sex (estimated β = 0.241; 95% CI [0.108, 0.329], p < 0.001) were associated with a worsened Δ BMI z-score at 12 months, while total hours with mental health provider (estimated β = -0.015; 95% CI [-0.030, -0.001], p = 0.049) was associated with an improved Δ BMI z-score at 12 months. Hours with an exercise counselor (estimated β = 0.023; 95% CI [0.008, 0.039], p = 0.003) were associated with improved HDL, while hours with a registered dietitian (estimated β = -0.026; 95% CI [-0.051, -0.001], p = 0.044) were associated with improved non-HDL cholesterol., Conclusions: Male sex and hours spent with a mental health provider, exercise counselor, and registered dietitian were related to significant improvements in several anthropometric and cardiometabolic health indicators at 12 months post-baseline., Competing Interests: Competing interests: PGM, AB, JPC, AL, MST, JH and LT have no competing interests. IZ is an advisory board member for Novo Nordisk, Dexcom, and Abbot Diabetes Care. JKH is a site investigator for studies sponsored by Levo Therapeutics, Canada, Rhythm Pharmaceuticals and Eli Lilly, and an advisory board member for Novo Nordisk. GDCB and LL are advisory board members for Novo Nordisk. KMM is an advisory board member for Novo Nordisk and Akcea Therapeutics, Canada. Ethics approval and consent to participate: The CANPWR study was approved by the following Research Ethics Boards: Hamilton Integrated Research Ethics Board, Conjoint Health Research Ethics Board (Calgary, Alberta), Research Ethics Board Trillium Health Partners, Health Research Ethics Board—Health Panel (Edmonton, Alberta), Children’s Hospital of Eastern Ontario Research Ethics Board, The Hospital for Sick Children Research Ethics Board, University of British Columbia Clinical Research Ethics Board, CHU Sainte-Justine Research Ethics Board, McGill University Health Centre Research Ethics Board—Pediatrics. All methods in the study were performed in accordance with the relevant guidelines and regulations of each Research Ethics Board. Written informed consent was obtained from the child’s parent or guardian, and participants provided assent., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Background and Hypothesis: While maternal schizophrenia is linked to chronic childhood medical conditions, little is known about the risk of acute asthma exacerbations among children whose mothers have schizophrenia. This population-based study used health data for all of Ontario, Canada to evaluate whether having a mother with schizophrenia was associated with increased risk of asthma exacerbations., Study Design: The study cohort included 385,989 children diagnosed with asthma from age 2 years onward, followed from the time of their asthma diagnosis up to a maximum of age 19 years. Children whose biological mother was diagnosed with schizophrenia prior to the child's asthma diagnosis (n = 1407) were compared children whose mother was not (n = 384,582). Study outcomes were asthma-related hospitalization, and separately, asthma-related emergency department (ED) visit, each up to a maximum child age of 19 years. First exacerbations were evaluated using Cox proportional hazards models, and recurrent exacerbations by Andersen-Gill regression, adjusted for covariates., Study Results: First hospitalization for an asthma exacerbation occurred in 76 (6.9 per 1000 person-years) vs. 19,679 (5.4 per 1000 person-years) children with and without maternal schizophrenia (adjusted hazard ratio [aHR] 1.21, 95 % CI 0.97-1.51). For first asthma-related ED exacerbations, the rates were 25.1 vs. 20.7 per 100 person-years (aHR 1.06, 95 % CI 0.93-1.21). The adjusted rate ratio (aRR) for recurrent hospitalizations for asthma exacerbations was 1.27 (95 % CI 0.98-1.66), and 1.11 (95 % CI 0.94-1.31) for recurrent asthma-related ED exacerbations., Conclusions: This study did not observe meaningful differences in acute care utilization for asthma exacerbations among children whose biological mothers had schizophrenia., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships outside of the submitted work, which may be considered as potential competing interests: Simone Vigod and Gillian Hanley report royalties from UptoDate Inc for authorship of materials related to depression and pregnancy. Eyal Cohen reports a relationship with the Ontario Ministry of Health as an advisory board member on public drug policy for the Committee to Evaluate Drugs. Katherine Morrison reports an advisory board member relationship with Novo Nordisk Inc and Rhythm Pharmaceuticals. Alison Holloway reports an advisory board member relationship with Taylored Biotherapeutics. Natasha Saunders reports an honorarium from the BMJ Publishing Group Ltd and Archives of Diseases in Childhood. The other authors have no relevant conflicts of interest to they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Context: During the COVID-19 pandemic, the United States relied on the public health workforce to control the spread of COVID-19 while continuing to provide foundational public health services. Facing longstanding staffing shortages, state, tribal, local, and territorial (STLT) public health agencies (PHAs) used various strategies and supports to surge the workforce in response to the pandemic., Objectives: The study explored (1) the types of strategies and supports STLT PHAs used to surge the public health workforce during the pandemic, (2) assessments of surge strategies and supports, and (3) approaches to using the range of surge strategies available., Design: We conducted 27 semi-structured interviews in 2023 and performed thematic analysis., Participants: Interviewees included STLT public health officials, leaders of organizations that directly supported the COVID-19 workforce surge, and public health workforce experts indirectly involved in the workforce surge., Results: To surge the workforce, interviewees relied on partnerships, staffing agencies, the National Guard, the Centers for Disease Control and Prevention Foundation's COVID-19 Corps, the Medical Reserve Corps, and other strategies. Interviewees valued strategies that rapidly engaged staff and volunteers at no cost to their PHA and flexible funding from the federal government to support surge efforts but noted shortcomings in the strategies and supports available. Interviewees described using multiple strategies simultaneously but noted challenges in implementing these strategies due to inadequate planning and insufficient staff and resources., Conclusion: The study underscores the need for STLT PHAs to establish mechanisms to surge the workforce as part of ongoing planning for emergency preparedness. Focus areas include building administrative and hiring capacity within STLT PHAs and sustaining partnerships and contractual agreements that helped fill staffing gaps during the pandemic. To support efforts to build workforce capacity to meet future surge management needs, STLT PHAs should consider creative solutions to attract and retain staff, as well as opportunities to engage students in public health work., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

The aryloxyamine motif is a prominent pharmacophore in drug design and development. While these biologically relevant structures could in principle be sustainably assembled from the base metal-catalyzed O-arylation of inexpensive and abundant amino alcohols with (hetero)aryl chlorides, reports of such challenging C-O bond formations with useful scope are lacking. In response, we report herein the hitherto unknown Ni-catalyzed C-O cross-coupling of N-protected amino alcohols (primary, secondary, and tertiary) with (hetero)aryl chlorides. Also presented are chemoselective sequential/telescoped C-N and C-O cross-couplings of the unprotected amino alcohol prolinol to afford an unsymmetrical diarylated product., (© 2024 The Author(s). Chemistry - A European Journal published by Wiley-VCH GmbH.)

A comparative experimental and computational study examining the interplay of the ancillary ligand structure and Ni oxidation state in the Ni-catalyzed C(sp 2 )-O cross-coupling of (hetero)aryl chlorides and primary or secondary aliphatic alcohols is presented, focusing on PAd-DalPhos ( L1 )-, CyPAd-DalPhos ( L2 )-, PAd2-DalPhos ( L3 )-, and DPPF ( L4 )-ligated [( L )NiCl] n ( n = 1 or 2) and ( L )Ni( o -tol)Cl precatalysts. Both L1 and L2 were found to outperform the other ligands examined, with the latter proving to be superior overall. While Ni(II) precatalysts generally outperformed Ni(I) species, in some instances the catalytic abilities of Ni(I) precatalysts were competitive with those of Ni(II). Density-functional theory calculations indicate the favorability of a Ni(0)/Ni(II) catalytic cycle featuring turnover-limiting C-O bond reductive elimination over a Ni(I)/Ni(III) cycle involving turnover-limiting C-Cl oxidative addition.

Background: Childhood obesity is an ongoing public health crisis, and recent clinical practice guidelines identify addressing the role of social inequities in the disparity of health among children with obesity as an area to address. This study aimed to assess the feasibility of a community navigation intervention in a pediatric weight management clinic., Methods: A single-center pilot randomized controlled trial (RCT) recruiting families from a tertiary hospital pediatric weight management program to evaluate the feasibility of a community navigation intervention. The primary feasibility outcomes were recruitment rates (goal to recruit 80% of the sample in 6 months), uptake of the intervention (goal > 80% of participants in the intervention group to have a visit with the navigator), and acceptability (goal > 90% of families in the intervention group complete all follow-up)., Results: Eighty participants completed the social needs screening, and 42 (52.5%) participants screened positive for an unmet social need. In the first 6 months of recruitment, 18 participants were recruited out of a goal of 40 participants (the recruitment rate was 45% vs. the goal of 80% in 6 months), and complete recruitment was achieved in 12 months. Of the 21 participants randomized to the intervention arm, 20 completed the intervention (uptake of intervention was 95% vs. goal 80%). Ten participants in the intervention arm completed all four planned follow-up study visits (the acceptability of follow-up was 48% vs. the goal of 90%)., Conclusion: We completed a pilot RCT of implementing a community navigator program in a pediatric weight management program. We found feasibility in the intervention's uptake but limited feasibility in recruiting participants and the acceptability of the follow-up., Trial Registration: Clinicaltrials.gov, NCT04711707, https://clinicaltrials.gov/ct2/show/NCT04711707., Competing Interests: Declarations Ethics approval and consent to participate The study received approval from Hamilton Integrated Research Ethics Board project #12697. Consent for publication Not applicable. Competing interests The authors have no conflicts of interest to disclose., (© 2024. The Author(s).)

Objective: To summarize the literature on pharmacotherapy for managing paediatric obesity., Methods: A systematic review and meta-analysis were conducted of randomized controlled trials (RCTs) with <18-year-olds of pharmacotherapeutic agents published up to November 2022. Estimates of effect for outcomes were presented relative to minimal important differences and GRADE certainty of evidence. We examined data on patient/proxy-reported outcome measures (PROMs), cardiometabolic risk factors, anthropometry and adverse events (AEs)., Results: Overall, 35 RCTs were included. Trials examined metformin (n = 26), glucagon-like peptide-1 receptor agonists (GLP1RAs) (n = 7) and a lipase inhibitor (orlistat; n = 2). Intervention duration varied (3-24 months). Metformin had little to no benefit on PROMs (e.g., health-related quality of life [HRQoL]; 6 RCTs), moderate reductions in triglycerides, a moderate decline in insulin resistance, a small to moderate decline in BMI z-score (BMIz) and a moderate increase in mild to moderate gastrointestinal AEs. Response to GLP1RAs was heterogeneous and results of subgroup analysis demonstrated variability of impact. Liraglutide (2 RCTs) resulted in a small reduction in HOMA-IR and BMIz, but little to no benefit on other outcomes. Exenatide (4 RCTs) had a moderate reduction on blood pressure and a small decrease in BMIz with little to no benefit on other outcomes. Semaglutide (1 RCT) had a small benefit on HRQoL, a small reduction on SBP, a moderate reduction on total cholesterol and LDL-cholesterol, a large reduction on triglyceride, and a very large decline in BMIz accompanied by a small increase in mild to moderate gastrointestinal AEs. Orlistat had a moderate reduction in DBP and little to no benefit in other outcomes measured, but had a very large increased risk of mild to moderate gastrointestinal AEs. Serious AEs were rare and for interventions with sufficent AE reporting, were considered not likely attributable to the interventions., Conclusion: Few studies examined the impact of pharmacotherapy on PROMs. There is evidence that metformin and GLP1RAs lead to important improvements in cardiometabolic and anthropometric outcomes while accompanied by mild to moderate AEs. Long-term effectiveness and safety of GLP1RAs remain to be evaluated., (© 2024 The Author(s). Pediatric Obesity published by John Wiley & Sons Ltd on behalf of World Obesity Federation.)

Objective: To summarize the literature on bariatric surgery for managing pediatric obesity, including intervention effects to improve patient-reported outcome measures (PROMs), cardiometabolic risk factors, anthropometry, and assess adverse events (AEs)., Methods: Eligible studies were published between January 2012 and January 2022 and included randomized controlled trials (RCTs) and observational (controlled and uncontrolled) studies before and after surgery with a mean age <18 years old. Outcomes and subgroups were selected a priori by stakeholders; estimates of effect for outcomes were presented relative to minimal important differences (MIDs) and GRADE certainty of evidence. We examined data on PROMs, cardiometabolic risk factors, anthropometry, and AEs. Subgroup analyses examined outcomes by follow-up duration and surgical technique, when possible., Results: Overall, 63 publications (43 original studies) met our inclusion criteria (n = 6128 participants; 66% female). Studies reported six different surgical techniques that were evaluated using uncontrolled single arm observational (n = 49), controlled observational (n = 13), and RCT (n = 1) designs. Most studies included short-term follow-up (<18 months) only. PROMs were measured in 12 (28%) studies. Surgery led to large improvements in health-related quality of life compared to baseline and control groups, and moderate to very large improvements in cardiometabolic risk factors compared to baseline. Large to very large improvements in BMIz were noted compared to baseline across all follow-up periods. There was limited evidence of AEs with most reporting mild or non-specific AEs; serious AEs were uncommon., Conclusion: Bariatric surgery demonstrated primarily moderate to very large improvements across diverse outcomes with limited evidence of AEs, albeit with low to moderate certainty of evidence., (© 2024 The Authors. Pediatric Obesity published by John Wiley & Sons Ltd on behalf of World Obesity Federation.)

Background: Maternal smoking has been linked to adverse health outcomes in newborns but the extent to which it impacts newborn health has not been quantified through an aggregated cord blood DNA methylation (DNAm) score. Here, we examine the feasibility of using cord blood DNAm scores leveraging large external studies as discovery samples to capture the epigenetic signature of maternal smoking and its influence on newborns in White European and South Asian populations., Methods: We first examined the association between individual CpGs and cigarette smoking during pregnancy, and smoking exposure in two White European birth cohorts (n=744). Leveraging established CpGs for maternal smoking, we constructed a cord blood epigenetic score of maternal smoking that was validated in one of the European-origin cohorts (n=347). This score was then tested for association with smoking status, secondary smoking exposure during pregnancy, and health outcomes in offspring measured after birth in an independent White European (n=397) and a South Asian birth cohort (n=504)., Results: Several previously reported genes for maternal smoking were supported, with the strongest and most consistent association signal from the GFI1 gene (6 CpGs with p<5 × 10 -5 ). The epigenetic maternal smoking score was strongly associated with smoking status during pregnancy (OR = 1.09 [1.07, 1.10], p=5.5 × 10 -33 ) and more hours of self-reported smoking exposure per week (1.93 [1.27, 2.58], p=7.8 × 10 -9 ) in White Europeans. However, it was not associated with self-reported exposure (p>0.05) among South Asians, likely due to a lack of smoking in this group. The same score was consistently associated with a smaller birth size (-0.37±0.12 cm, p=0.0023) in the South Asian cohort and a lower birth weight (-0.043±0.013 kg, p=0.0011) in the combined cohorts., Conclusions: This cord blood epigenetic score can help identify babies exposed to maternal smoking and assess its long-term impact on growth. Notably, these results indicate a consistent association between the DNAm signature of maternal smoking and a small body size and low birth weight in newborns, in both White European mothers who exhibited some amount of smoking and in South Asian mothers who themselves were not active smokers., Funding: This study was funded by the Canadian Institutes of Health Research Metabolomics Team Grant: MWG-146332., Competing Interests: WD, NC, NC, SA, Rd, AL, KM, SA, PS, ST, TM, KT, PM, MA, ES, GP, SA No competing interests declared, (© 2024, Deng et al.)

Background: Anxiety and depression are among the most common and debilitating psychiatric disorders affecting youth, with both related to increased suicide risk. While rates of youth anxiety and depression were increasing before the COVID-19 pandemic, the pandemic further negatively impacted adolescent mental health. Unfortunately, few studies have examined prevalence of these concerns among early adolescents (ages 10-13) longitudinally during the pandemic., Method: The current study examined self-reported anxiety and depression symptoms, and suicidal ideation amongst a general pediatrics population of 11- to 13-year-olds (n = 623) from March through September 2020 (early-pandemic) and approximately 7 months later (September 2020 through May 2021; mid-pandemic). Paired samples proportions were used to examine changes in prevalence of moderate to severe anxiety, depression, and suicidal ideation from early- to mid-pandemic., Results: Results highlight high initial rates and stability in anxiety and suicidal ideation, as well as a significant increase in depression (42.9% increase; p < .05) among the full sample during the COVID-19 pandemic. Prevalance of concerns were greatest for females and Hispanic youth during the early-pandemic, and generally highest for females and Medicaid insured youth at mid-pandemic., Discussion: Results extend recent research and underscore the need for continued monitoring of mental health concerns across development for youth who grew up during the COVID-19 pandemic; highlighting the need for sustainable, effective, and accessible early detection, prevention, and intervention strategies. Improving these services is critical to support youth who experienced pandemic-related stressors, and to prepare for supporting youth during future disruptive and isolating events., (© 2024 Foundation for Professionals in Services to Adolescents.)

Purpose: 1) To explore how children with spina bifida (SB) and their parents understand bodyweight, health and weight management; and 2) To identify what services and supports children with SB and their families feel are most appropriate to help them manage their health and weight., Methods: The study used interpretive description within a qualitative design. Participants were children with SB (aged 10-18) attending two Canadian SB clinics and their parents. Data were collected through individual interviews and analyzed using inductive thematic analysis., Results: Five children and five parents participated in the study. Children and parents had a weight-centric approach to health, which was related to the child's mobility. Weight was considered to be under individual control and mostly through diet. Trusting relationships between healthcare providers, children and families were important to discuss weight in a non-judgemental manner. Children should be involved in setting meaningful and achievable weight management goals., Conclusion: Greater knowledge of how children with SB and their families understand weight and health offers opportunities for non-judgemental discussions about their needs and wishes. Helping families to place more value on health over weight may reduce feelings of stigma, while allowing children to develop some autonomy over health-related decisions.

Background: Chronic stress is an important risk factor in the development of obesity. While research suggests chronic stress is linked to excess weight gain in children, the biological or behavioral mechanisms are poorly understood., Objective: The objectives of the Family Stress Study are to examine behavioral and biological pathways through which chronic stress exposure (including stress from COVID-19) may be associated with adiposity in young children, and to determine if factors such as child sex, caregiver-child relationship quality, caregiver education, and caregiver self-regulation moderate the association between chronic stress and child adiposity., Methods: The Family Stress Study is a prospective cohort study of families recruited from 2 Canadian sites: the University of Guelph in Guelph, Ontario, and McMaster University in Hamilton, Ontario. Participants will be observed for 2 years and were eligible to participate if they had at least one child (aged 2-6 years) and no plans to move from the area within the next 3 years. Study questionnaires and measures were completed remotely at baseline and will be assessed using the same methods at 1- and 2-year follow-ups. At each time point, caregivers measure and report their child's height, weight, and waist circumference, collect a hair sample for cortisol analysis, and fit their child with an activity monitor to assess the child's physical activity and sleep. Caregivers also complete a web-based health and behaviors survey with questions about family demographics, family stress, their own weight-related behaviors, and their child's mental health, as well as a 1-day dietary assessment for their child., Results: Enrollment for this study was completed in December 2021. The final second-year follow-up was completed in April 2024. This study's sample includes 359 families (359 children, 359 female caregivers, and 179 male caregivers). The children's mean (SD) age is 3.9 years (1.2 years) and 51% (n=182) are female. Approximately 74% (n=263) of children and 80% (n=431) of caregivers identify as White. Approximately 34% (n=184) of caregivers have a college diploma or less and nearly 93% (n=499) are married or cohabiting with a partner. Nearly half (n=172, 47%) of the families have an annual household income ≥CAD $100,000 (an average exchange rate of 1 CAD=0.737626 USD applies). Data cleaning and analysis are ongoing as of manuscript publication., Conclusions: Despite public health restrictions from COVID-19, the Family Stress Study was successful in recruiting and using remote data collection to successfully engage families in this study. The results from this study will help identify the direction and relative contributions of the biological and behavioral pathways linking chronic stress and adiposity. These findings will aid in the development of effective interventions designed to modify these pathways and reduce obesity risk in children., Trial Registration: ClinicalTrials.gov NCT05534711; https://clinicaltrials.gov/study/NCT05534711., International Registered Report Identifier (irrid): DERR1-10.2196/48549., (©Shannon M Pare, Elizabeth Gunn, Katherine M Morrison, Alison L Miller, Alison M Duncan, Andrea C Buchholz, David W L Ma, Paul F Tremblay, Lori Ann Vallis, Nicola J Mercer, Jess Haines. Originally published in JMIR Research Protocols (https://www.researchprotocols.org), 20.06.2024.)

Background: Epigenetic modifications, particularly DNA methylation (DNAm) in cord blood, are an important biological marker of how external exposures during gestation can influence the in-utero environment and subsequent offspring development. Despite the recognized importance of DNAm during gestation, comparative studies to determine the consistency of these epigenetic signals across different ethnic groups are largely absent. To address this gap, we first performed epigenome-wide association studies (EWAS) of gestational age (GA) using newborn cord blood DNAm comparatively in a white European (n = 342) and a South Asian (n = 490) birth cohort living in Canada. Then, we capitalized on established cord blood epigenetic GA clocks to examine the associations between maternal exposures, offspring characteristics and epigenetic GA, as well as GA acceleration, defined as the residual difference between epigenetic and chronological GA at birth., Results: Individual EWASs confirmed 1,211 and 1,543 differentially methylated CpGs previously reported to be associated with GA, in white European and South Asian cohorts, respectively, with a similar distribution of effects. We confirmed that Bohlin's cord blood GA clock was robustly correlated with GA in white Europeans (r = 0.71; p = 6.0 × 10 -54 ) and South Asians (r = 0.66; p = 6.9 × 10 -64 ). In both cohorts, Bohlin's clock was positively associated with newborn weight and length and negatively associated with parity, newborn female sex, and gestational diabetes. Exclusive to South Asians, the GA clock was positively associated with the newborn ponderal index, while pre-pregnancy weight and gestational weight gain were strongly predictive of increased epigenetic GA in white Europeans. Important predictors of GA acceleration included gestational diabetes mellitus, newborn sex, and parity in both cohorts., Conclusions: These results demonstrate the consistent DNAm signatures of GA and the utility of Bohlin's GA clock across the two populations. Although the overall pattern of DNAm is similar, its connections with the mother's environment and the baby's anthropometrics can differ between the two groups. Further research is needed to understand these unique relationships., (© 2024. The Author(s).)

Objective: Red and processed meat is considered risk factors of gestational diabetes mellitus (GDM), but the evidence is inconclusive. We aimed to examine the association between red and processed meat intake and odds of GDM among South Asian and White European women living in Canada., Methods: This is a cross-sectional analysis of pregnant women from two birth cohorts: SouTh Asian biRth cohorT (START; n = 976) and Family Atherosclerosis Monitoring In earLY life (FAMILY; n = 581). Dietary intake was assessed using a validated 169-item semi-quantitative food-frequency questionnaire (FFQ). Multivariate logistic regression models were used to examine the associations between gestational diabetes and: 1) total red and processed meat; 2) unprocessed red meat; 3) processed meat and GDM after adjustment for potential confounders., Results: There were 241 GDM cases in START and 91 in FAMILY. The median total red and processed meat intake were 1.5 g/d (START) and 52.8 g/d (FAMILY). In START, the multivariable-adjusted odds ratio (OR) showed neither lower nor higher intakes of unprocessed red meat (p-trend = 0.68), processed meat (p-trend = 0.90), or total red and processed meat (p-trend = 0.44), were associated with increased odds of GDM, when compared with medium intake. Similar results were observed in FAMILY except for processed meat intake [OR = 0.94 (95% CI 0.47-1.91), for medium versus low and OR = 1.51 (95% CI 0.77-2.29) for medium versus high; p-trend = 0.18] after adjusting for additional dietary factors such as the diet quality score, total fiber, saturated fat and glycemic load., Conclusion: Medium compared with low or high red and processed meat intake is not associated with GDM in White Europeans and South Asians living in Canada., Competing Interests: Hertzel C. Gerstein holds the McMaster-Sanofi Population Health Institute Chair in Diabetes Research and Care. He reports research grants from Eli Lilly, AstraZeneca, Novo Nordisk, and Sanofi; honoraria for speaking from AstraZeneca, Boehringer Ingelheim, Eli Lilly, Novo Nordisk, DKSH, Zuellig, Roche, Sanofi, Jiangsu Hanson, and Carbon Brand; and consulting fees from Abbott, Eli Lilly, Novo Nordisk, Sanofi, Kowa, Pfizer, Hanmi and Viatris. Russell J. de Souza has served as an external resource person to the World Health Organization’s Nutrition Guidelines Advisory Group on trans fats, saturated fats, and polyunsaturated fats. The WHO paid for his travel and accommodation to attend meetings from 2012-2017 to present and discuss this work. He has also done contract research for the Canadian Institutes of Health Research’s Institute of Nutrition, Metabolism, and Diabetes, Health Canada, and the World Health Organization for which he received remuneration. He has received speaker’s fees from the University of Toronto, and McMaster Children’s Hospital. He has held grants from the Canadian Institutes of Health Research, Canadian Foundation for Dietetic Research, Population Health Research Institute, and Hamilton Health Sciences Corporation as a principal investigator, and is a co-investigator on several funded team grants from the Canadian Institutes of Health Research. He serves as a member of the Nutrition Science Advisory Committee to Health Canada (Government of Canada), a co-opted member of the Scientific Advisory Committee on Nutrition (SACN) Subgroup on the Framework for the Evaluation of Evidence (Public Health England), and as an independent director of the Helderleigh Foundation (Canada). These affiliations do not alter our adherence to PLOS ONE policies on sharing data and materials. START has not received funding/assistance from a commercial organization., (Copyright: © 2024 Stennett et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Children with disabilities are twice as likely to have overweight/obesity than their typically developing peers. Higher weights in these individuals may compound challenges already experienced with their disability, including mobility and activities of daily living. However, children with disabilities often find it challenging accessing weight management care. It is therefore important to understand the experiences and needs of the health care professionals (HCPs) who work in specialized pediatric weight management clinics about providing weight-related care to children with disabilities. Methods: Employing an interpretive description approach, purposeful sampling was used to recruit 17 HCP participants working in pediatric weight management settings in Canada. Qualitative semistructured interviews were conducted online or via telephone. All interview recordings were transcribed and a reflexive thematic analysis approach was used to develop themes from the data. Results: Four themes were developed: (1) infrequent referrals leads to a lack of experience with children with disabilities; (2) adapting group-based clinics can be challenging; (3) perceived lack of disability-specific knowledge causes moral distress; and (4) disability-specific training and greater interdisciplinary collaboration are desired. Conclusions: This work identifies the urgent need for more evidence-based, specialized, weight-related treatment options for children with disabilities, as well as more support for HCPs working in existing programs.

Nickel-catalyzed cross-couplings of (hetero)aryl electrophiles with a diversity of nucleophiles (nitrogen, oxygen, carbon, and others) have evolved into competitive alternatives to well-established palladium- and copper-based protocols for the synthesis of (hetero)aryl products, including (hetero)anilines and (hetero)aryl ethers. A survey of the literature reveals that the use of cage phosphine (CgP) 'DalPhos' (DALhousie PHOSphine) bisphosphine-type ligands operating under thermal conditions currently offers the most broad substrate scope in nickel-catalyzed cross-couplings of this type, especially involving (hetero)aryl chlorides and phenol-derived electrophiles. The development and application of these DalPhos ligands is described in a ligand-specific manner that is intended to serve as a guide for the synthetic chemistry end-user., Competing Interests: The authors declare the following competing financial interests: Dalhousie University has filed patents on the DalPhos ancillary ligands and derived nickel pre-catalysts used in this work, from which royalty payments may be derived., (This journal is © The Royal Society of Chemistry.)

Context: Compared with the relatively benign effects of increased subcutaneous adipose tissue (SAT), increased visceral adipose tissue (VAT) volume is a causal risk factor for hypertension, hyperlipidemia, type 2 diabetes, and cardiovascular disease. In rodents, increased VAT volume and triglyceride density and ectopic lipid accumulation in kidneys and liver have been induced by alterations in the gut microbiome. However, few studies have characterized these relationships in humans., Objective: To evaluate the tissue triglyceride content of VAT and SAT, liver, kidneys, and pancreas in male and female adults and assess associations with markers of glucose tolerance, serum insulin, and lipids and characteristics of the gut microbiome., Methods: Cross-sectional observational study of healthy human adults (n = 60) at a clinical research center. Body mass index (BMI), body composition, and oral glucose tolerance were assessed. Microbiome analysis was conducted on stool samples using 16S rRNA v3 amplicon sequencing. The triglyceride content of VAT, SAT, liver, kidney and pancreas were determined by assessing proton density fat fraction (PDFF) with magnetic resonance imaging (MRI)., Results: Higher VAT PDFF and the ratio of VAT to SAT PDFF were related to higher BMI, HbA1c, HOMA-IR, non-high-density lipoprotein cholesterol, plasma triglycerides, low-density lipoprotein (LDL) cholesterol, and lower high-density lipoprotein (HDL) cholesterol. A higher VAT PDFF and VAT to SAT PDFF ratio were associated with lower alpha diversity and altered beta diversity of the gut microbiome. Differences in VAT were associated with higher relative abundance of the phylum Firmicutes, lower relative abundance of the phylum Bacteroidetes, and enrichment of the bacterial genera Dorea, Streptococcus, and Solobacterium., Conclusion: VAT PDFF measured with MRI is related to impaired glucose homeostasis, dyslipidemia, and differences in the gut microbiome, independently of the total body fat percentage., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Childhood obesity is a global health concern affecting over 150 million children worldwide, with projections of a rise to 206 million by 2025. Understanding the mechanisms underlying this epidemic is crucial for developing effective interventions. In this study, we investigated circulating levels of Growth Differentiation Factor 10 (GDF10), a novel regulator of adipogenesis. Previous studies report diminished circulating GDF10 levels contribute to obesity and hepatic steatosis in mice. To further understand the role of plasma GDF10 in childhood obesity, a prospective case-control study was conducted. Using an enzyme-linked immunosorbent assay, plasma GDF10 levels were measured in children aged 5-17 years of age with normal (n = 36) and increased (n = 56) body mass index (BMI). Subsequently, plasma GDF10 levels were compared to various cardio-metabolic parameters. Children with increased BMI exhibit significantly lower levels of plasma GDF10 compared to children with normal BMI (p < 0.05). This study not only supports previous mouse data but is the first to report that lower levels of GDF10 is associated with childhood obesity, providing an important human connection for the relevance of GDF10 in obesity. Furthermore, this study revealed a significant correlation between low plasma GDF10 levels and elevated LDL-cholesterol and total cholesterol levels dependent on BMI (95% CI, p < 0.05). This study supports the hypothesis that children with obesity display lower plasma levels of GDF10, which correlates with elevated cholesterol levels. These insights shed light on potential mechanisms contributing to childhood obesity and may lead to future therapeutic interventions targeting GDF10 to mitigate adverse effects of adipogenesis in cardiometabolic health., (© 2024. The Author(s).)

Background: The pan-Canadian Maternal-Infant Research on Environmental Chemicals (MIREC) study was established to determine whether maternal environmental chemical exposures were associated with adverse pregnancy outcomes in 2001 pregnant women., Objectives: The MIREC-Child Development (CD PLUS) study followed this cohort with the goal of assessing the potential effects of prenatal exposures on anthropometry and neurodevelopment in early childhood., Population: MIREC families with children between the ages of 15 months and 5 years who had agreed to be contacted for future research (n = 1459) were invited to participate in MIREC-CD PLUS which combines data collected from an online Maternal Self-Administered Questionnaire with biomonitoring and neurodevelopment data collected from two in-person visits., Preliminary Results: Between April 2013 and March 2015, 803 children participated in the Biomonitoring visit where we collected anthropometric measures, blood, and urine from the children. The Behavioural Assessment System for Children-2, Behaviour Rating Inventory of Executive Function, MacArthur-Bates Communicative Development Inventories and the Communication subscale of the Adaptive Behaviour Scale from the Bayley Scales of Infant and Toddler Development-III are available on close to 900 children. There were 610 singleton children who completed in-person visits for neurodevelopment assessments including the Social Responsiveness Scale, Wechsler Preschool Primary Scale of Intelligence-III and NEuroPSYchological assessments (NEPSY). Currently, we are following the cohort into early adolescence to measure the impact of early life exposures on endocrine and metabolic function (MIREC-ENDO)., Conclusions: Data collection for the MIREC-CD PLUS study is complete and analysis of the data continues. We are now extending the follow-up of the cohort into adolescence to measure the impact of early life exposures on endocrine and metabolic function (MIREC-ENDO). MIREC-CD PLUS is limited by loss to follow-up and the fact that mothers are predominately of higher socioeconomic status and 'White' ethnicity, which limits our generalizability. However, the depth of biomonitoring and clinical measures in MIREC provides a platform to examine associations of prenatal, infancy and childhood exposures with child growth and development., (© 2023 His Majesty the King in Right of Canada and The Authors. Paediatric and Perinatal Epidemiology published by John Wiley & Sons Ltd. Reproduced with the permission of the Minister of Health.)

Association between obstructive lung function impairment with higher cIMT is present in childhood after accounting for common risk factors. This suggests that a developmental link between obstructive lung diseases and CVD may have its origin in early life. https://bit.ly/4657s2b., Competing Interests: Conflict of interest: The authors declare no competing interests., (Copyright ©The authors 2023.)

The study objective is to evaluate the influence of attrition from a paediatric weight management program (PWM) on health indicators over a 2-year period. In this observational study, children and youth with obesity were recruited at entry into a family-based behaviour modification PWM and had four research study visits, independent of clinic visits, over 2 years. Participants were divided into attrition groups based on length of clinic enrolment. Body composition, cardiometabolic health and health-related quality of life (HRQoL) were assessed. Among 269 children enrolled, 19% had no clinic treatment visit, 16% had treatment visits only up to 6 months, 23% up to 1 year and 42% had at least one clinic visit after 1 year (No Attrition). Greater declines in BMI z-score and body fat were seen at 2 years in children with No Attrition, while improvements in HRQoL were similar for all attrition groups. Children who attended at least one treatment visit reported improved HRQoL up to 2 years, regardless of duration in clinic. In contrast, declines in body fat and BMI z-score were greater at 2 years for those with at least one visit after 1 year. Continued efforts to reduce attrition are likely to improve anthropometric health outcomes during PWM., (© 2023 The Authors. Clinical Obesity published by John Wiley & Sons Ltd on behalf of World Obesity Federation.)

Purpose: Mobile health (mHealth) apps may support improved health behavior practice among youth living in larger bodies. However, long-term use is low, limiting effectiveness. This study evaluated whether youths' motivation, satisfaction, engagement with social features, or parent co-participation supported long-term use of an app named Aim2Be. Methods: A secondary analysis of two versions of Aim2Be (preteen and teen versions) using covariate-adjusted multivariable regression was conducted. We evaluated associations between social support features (a virtual coach, a social poll, or a social wall), parent co-participation (time spent in the parent app), and app satisfaction on use (time spent in Aim2Be). Models were stratified by age and satisfaction was explored as a moderator. Results: Preteens ( n  = 83) engagement with the social poll ( β  = 0.26, p  < 0.001), virtual health coach ( β  = 0.24, p  = 0.01), app satisfaction ( β  = 0.31, p  = 0.01), and parent co-participation ( β  = 0.24, p  = 0.01) predicted use. In teens ( n  = 90), engagement with the virtual coach ( β  = 0.31, p  < 0.001) and full utilization of social wall features ( β  = 0.41, p  < 0.001) predicted use. Furthermore, satisfaction moderated the effects of partial utilization of the social wall among teens ( β  = 0.32 p  = 0.02). Conclusion: Social support in mHealth apps may impact users differently depending on age. Features that include health professionals or peers may be more advantageous across ages. App developers should consider age when designing interventions. Clinical Trial Registration NCT03651284.

Background: Recruitment of participants continues to be a challenge that researchers must overcome to yield successful study results. Over the past decade, there has been a dramatic increase in the use of social media platforms to recruit research participants. We conducted a secondary analysis of the Aim2Be randomized controlled trial (RCT) to examine if there was variability between participants recruited via social media versus pediatric obesity clinics., Methods: Parents and their children living with overweight or obesity were recruited through social media (i.e., Facebook advertisements) (n = 119) or pediatric obesity management clinics (n = 95) to participate in the Aim2Be RCT. We compared recruitment costs, recruitment rate, participant retention, intervention engagement, obesity-related risk factors, and behavioral habits., Results: Facebook recruitment resulted in more participant contacts, but higher attrition during 'high effort' stages of the recruitment process. Group differences emerged regarding costs (Facebook: $407 versus clinics: $699). There were no group differences in participant retention or intervention engagement. Families recruited from Facebook were younger parents (42.6 versus 46.0 years; p < 0.001) and children (12.2 versus 13.9 years; p < 0.001), a higher percentage male children, and fewer had previously participated in a pediatric weight management program. Parents recruited from Facebook self-reported greater screen time for themselves, and their children reported lower physical activity levels and higher caloric and sugar intake., Conclusions: Social media and clinical site recruitment are complementary strategies that appear to draw in families with different profiles, but regardless of how they were recruited, all families had the potential to benefit from pediatric obesity management., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objectives: The prevalence of pediatric diabetes is increasing. Dyslipidemia is an important modifiable cardiovascular disease risk factor often present in children with diabetes. In this study, we evaluated the adherence to Diabetes Canada 2018 lipid screening guidelines in a pediatric diabetes program to determine the prevalence of dyslipidemia in youth with diabetes and to identify risk factors related to dyslipidemia., Methods: This retrospective chart review included patients at McMaster Children's Hospital with diabetes (types 1 and 2), who were at least 12 years of age as of January 1, 2019. Extracted data included age, sex, family history of diabetes or dyslipidemia, date of diagnosis, body mass index, glycemia monitoring system used, lipid profile, glycated hemoglobin (A1C), and thyroid-stimulating hormone values at the time the lipid profile was measured. Statistical methods included descriptive statistics and logistic regression modelling., Results: Of the 305 patients included, 61% had a lipid profile measured according to guidelines, 29% had lipid screening completed outside of the recommended window, and 10% had no lipid profile on record. Among screened patients, 45% had dyslipidemia, most commonly hypertriglyceridemia (35%). Dyslipidemia was highest amongst those with type 2 diabetes, obesity, older age, short duration of diabetes, higher A1C, and those who used capillary blood glucose for monitoring (p<0.05)., Conclusions: A high proportion of patients were screened for dyslipidemia, but many outside the recommended window. Dyslipidemia is highly prevalent in this patient population and was associated with the presence of obesity, but 44% of patients without obesity also had dyslipidemia., (Copyright © 2023 Canadian Diabetes Association. Published by Elsevier Inc. All rights reserved.)

Background: Studies investigating neonatal outcomes following intrapartum antibiotic exposure show conflicting results., Methods: Data were collected prospectively in pregnancy to 1-year-of-age, from 212 mother-infant pairs. Adjusted multivariable regression models estimated relationships following exposure to intrapartum antibiotics among vaginally-born, full-term infants and outcomes related to growth, atopic disease, gastrointestinal symptoms, and sleep at 1-year., Results: Intrapartum antibiotic exposure (n = 40) was not associated with mass, ponderal index, BMI z-score (1- year), lean mass index (5-months) or height. Antibiotic exposure in labour ≥4-h was associated with increase in fat mass index at 5-months (β 0.42 [95% CI: 0.03, 0.80], p = 0.03). Intrapartum antibiotic was associated with atopy in the first year (OR: 2.93 [95% CI: 1.34, 6.43], p = 0.007). Antibiotic exposure during intrapartum or day 1-7 was associated with newborn fungal infection requiring antifungal therapy (OR 3.04 [95% CI: 1.14, 8.10], p = 0.026), and number of fungal infections (IRR: 2.90 [95% CI: 1.02, 8.27], p = 0.046)., Conclusion: Intrapartum and early life exposure to antibiotics were independently associated with measures of growth, atopy, and fungal infections suggesting that intrapartum and early neonatal antibiotics be used prudently following careful risk-benefit analysis., Impact: This prospective study: Shows a shift in fat mass index at 5 months associated with antibiotic administration ≥4 h in labour; an earlier age than previously reported; Shows atopy reported less frequently among those not exposed to intrapartum antibiotics; Supports earlier research of increased likelihood of fungal infection following exposure to intrapartum or early-life antibiotics; Adds to growing evidence that antibiotics used intrapartum and in early neonatal periods influence longer-term outcomes for infants. Suggests that use of intrapartum and early neonatal antibiotics should be used prudently after careful consideration of risk and benefit., (© 2023. The Author(s), under exclusive licence to the International Pediatric Research Foundation, Inc.)

To examine the (i) relationships between various body mass index (BMI)-derived metrics for measuring severe obesity (SO) over time based the Centers for Disease Control and Prevention (CDC) and World Health Organization (WHO) references and (ii) ability of these metrics to discriminate children and adolescents based on the presence of cardiometabolic risk factors. In this cohort study completed from 2013 to 2021, we examined data from 3- to 18-year-olds enrolled in the CANadian Pediatric Weight management Registry. Anthropometric data were used to create nine BMI-derived metrics based on the CDC and WHO references. Cardiometabolic risk factors were examined, including dysglycemia, dyslipidemia, and elevated blood pressure. Analyses included Pearson correlations, intraclass correlation coefficients (ICC), and receiver operator characteristic area-under-the-curve (ROC AUC). Our sample included 1,288 participants (n = 666 [52%] girls; n = 874 [68%] white). The prevalence of SO varied from 60-67%, depending on the definition. Most BMI-derived metrics were positively and significantly related to one another (r = 0.45-1.00); ICCs revealed high tracking (0.90-0.94). ROC AUC analyses showed CDC and WHO metrics had a modest ability to discriminate the presence of cardiometabolic risk factors, which improved slightly with increasing numbers of risk factors. Overall, most BMI-derived metrics rated poorly in identifying presence of cardiometabolic risk factors.    Conclusion: CDC BMI percent of the 95 th percentile and WHO BMIz performed similarly as measures of SO, although neither showed particularly impressive discrimination. They appear to be interchangeable in clinical care and research in pediatrics, but there is a need for a universal standard. WHO BMIz may be useful for clinicians and researchers from countries that recommend using the WHO growth reference. What is Known: • Severe obesity in pediatrics is a global health issue. • Few reports have evaluated body mass index (BMI)-derived metrics based on the World Health Organization growth reference. What is New: • Our analyses showed that the Centers for Disease Control and Prevention BMI percent of the 95 th percentile and World Health Organization (WHO) BMI z-score (BMIz) performed similarly as measures of severe obesity in pediatrics. • WHO BMIz should be a useful metric to measure severe obesity for clinicians and researchers from countries that recommend using the WHO growth reference., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

A systematic evaluation of competitive bisphosphine/Ni-catalyzed C-N versus C-O cross-couplings involving model compounds enabled development of hitherto unknown chemoselective O- and N-arylation of amino alcohols with (hetero)aryl chloride electrophiles, without recourse to protection group chemistry. Use of the CyPAd-DalPhos pre-catalyst C2 enabled particularly challenging O-arylation chemoselectivity in amino alcohols featuring branched primary and secondary alkylamine groups, while selective N-arylation was observed in substrates featuring less-hindered linear alkylamine and aniline reacting groups. Useful reaction scope in the (hetero)aryl chloride was achieved throughout, and the ability to conduct such transformations using benchtop handling of materials is demonstrated., (© 2023 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH.)

Worldwide, rates of metabolic diseases are rapidly increasing and environmental exposure to pesticides, pollutants and/or other chemicals may play a role. Reductions in Brown Adipose Tissue (BAT) thermogenesis, mediated in part by uncoupling protein 1 (Ucp1), are associated with metabolic diseases. In the current study, we investigated whether the pesticide deltamethrin (0.01-1 mg/kg bw/day) incorporated into a high-fat diet and fed to mice housed at either room temperature (21°C) or thermoneutrality (29°C) would suppress BAT activity and accelerate the development of metabolic disease. Importantly, thermoneutrality allows for more accurate modeling of human metabolic disease. We found that, 0.01 mg/kg bw/day of deltamethrin induced weight loss, improved insulin sensitivity and increased energy expenditure, effects that were associated with increases in physical activity. In contrast, exposure to 0.1 and 1 mg/kg bw/day deltamethrin had no effect on any of the parameters examined. Deltamethrin treatment in mice did not alter molecular markers of BAT thermogenesis, despite observing suppression of UCP1 expression in cultured brown adipocytes. These data indicate that while deltamethrin inhibits UCP1 expression in vitro, 16wks exposure does not alter BAT thermogenesis markers nor exacerbates the development of obesity and insulin resistance in mice., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Ltd.)

Evidence supports a complex interplay of gut microbiome and host metabolism as regulators of obesity. The metabolic phenotype and microbial metabolism of host diet may also contribute to greater obesity risk in children early in life. This study aimed to identify features that discriminated overweight/obese from normal weight infants by integrating gut microbiome and serum metabolome profiles. This prospective analysis included 50 South Asian children living in Canada, selected from the SouTh Asian biRth cohorT (START). Serum metabolites were measured by multisegment injection-capillary electrophoresis-mass spectrometry and the relative abundance of bacterial 16S rRNA gene amplicon sequence variant was evaluated at 1 year. Cumulative body mass index (BMI AUC ) and skinfold thickness (SSF AUC ) scores were calculated from birth to 3 years as the total area under the growth curve (AUC). BMI AUC and/or SSF AUC >85th percentile was used to define overweight/obesity. Data Integration Analysis for Biomarker discovery using Latent cOmponent (DIABLO) was used to identify discriminant features associated with childhood overweight/obesity. The associations between identified features and anthropometric measures were examined using logistic regression. Circulating metabolites including glutamic acid, acetylcarnitine, carnitine, and threonine were positively, whereas γ-aminobutyric acid (GABA), symmetric dimethylarginine (SDMA), and asymmetric dimethylarginine (ADMA) were negatively associated with childhood overweight/obesity. The abundance of the Pseudobutyrivibrio and Lactobacillus genera were positively, and Clostridium sensu stricto 1 and Akkermansia were negatively associated with childhood overweight/obesity. Integrative analysis revealed that Akkermansia was positively whereas Lactobacillus was inversely correlated with GABA and SDMA, and Pseudobutyrivibrio was inversely correlated with GABA. This study provides insights into metabolic and microbial signatures which may regulate satiety, energy metabolism, inflammatory processes, and/or gut barrier function, and therefore, obesity trajectories in childhood. Understanding the functional capacity of these molecular features and potentially modifiable risk factors such as dietary exposures early in life may offer a novel approach for preventing childhood obesity., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. RJ de Souza has served as an external resource person to the World Health Organization’s Nutrition Guidelines Advisory Group on trans fats, saturated fats, and polyunsaturated fats. The WHO paid for his travel and accommodation to attend meetings from 2012-2017 to present and discuss this work. He has presented updates of this work to the WHO in 2022. He has also done contract research for the Canadian Institutes of Health Research’s Institute of Nutrition, Metabolism, and Diabetes, Health Canada, and the World Health Organization for which he received remuneration. He has received speaker’s fees from the University of Toronto, and McMaster Children’s Hospital. He has served as an independent director of the Helderleigh Foundation (Canada). He serves as a member of the Nutrition Science Advisory Committee to Health Canada (Government of Canada), co-chair of the Method working group of the ADA/EASD Precision Medicine in Diabetes group, and is a co-opted member of the Scientific Advisory Committee on Nutrition (SACN) Subgroup on the Framework for the Evaluation of Evidence (Public Health England). He has held grants from the 10.13039/501100000024Canadian Institutes of Health Research, 10.13039/501100000203Canadian Foundation for Dietetic Research, Population Health Research Institute, and Hamilton Health Sciences Corporation as a principal investigator, and is a co-investigator on several funded team grants from the 10.13039/501100000024Canadian Institutes of Health Research., (© 2023 Published by Elsevier Ltd.)

Background: Childhood obesity is a global health concern and can lead to lifetime cardiometabolic disease. New advances in metabolomics can provide biochemical insights into the early development of obesity, so we aimed to characterize serum metabolites associated with overweight and adiposity in early childhood and to stratify associations by sex., Methods: Nontargeted metabolite profiling was conducted in the Canadian CHILD birth cohort (discovery cohort) at age 5 years (n = 900) by multisegment injection-capillary electrophoresis-mass spectrometry. Clinical outcome was defined using novel combined measures of overweight (WHO-standardized body mass index ≥ 85th percentile) and/or adiposity (waist circumference ≥ 90th percentile). Associations between circulating metabolites and child overweight/adiposity (binary and continuous outcomes) were determined by multivariable linear and logistic regression, adjusting for covariates and false discovery rate, and by subsequent sex-stratified analysis. Replication was assessed in an independent replication cohort called FAMILY at age 5 years (n = 456)., Results: In the discovery cohort, each standard deviation (SD) increment of branched-chain and aromatic amino acids, glutamic acid, threonine, and oxoproline was associated with 20-28% increased odds of overweight/adiposity, whereas each SD increment of the glutamine/glutamic acid ratio was associated with 20% decreased odds. All associations were significant in females but not in males in sex-stratified analyses, except for oxoproline that was not significant in either subgroup. Similar outcomes were confirmed in the replication cohort, where associations of aromatic amino acids, leucine, glutamic acid, and the glutamine/glutamic acid ratio with childhood overweight/adiposity were independently replicated., Conclusions: Our findings show the utility of combining measures of both overweight and adiposity in young children. Childhood overweight/adiposity at age 5 years has a specific serum metabolic phenotype, with the profile being more prominent in females compared to males., (© 2023. The Author(s).)

Objectives: A woman's food choices during pregnancy may be associated with her offspring's food choices. Several studies support an association between childhood sugary beverage (SB) consumption and poor cardiometabolic health. This study aimed to assess the association of maternal SB consumption during pregnancy and later, with her offspring's SB consumption in early infancy and childhood., Methods: A total of 1945 women and 1595 children participating in 3 Canadian studies reported SB consumption during pregnancy, at 2 years of age, and/or at school age (5 to 8 years old). Mother and offspring SB intakes were self-reported by mothers. Multivariable linear regression analyses were conducted within each cohort and cohort data were combined using fixed effect meta-analyses., Results: Maternal SB consumption during pregnancy was associated with higher offspring SB consumption at 2 years of age (standardized β = 0.19 predicted change in the number of standard deviations of offspring SB intake for an increase of 1 standard deviation in maternal serving [95% CI: 0.16 to 0.22]). Concurrent maternal SB consumption was associated with higher offspring SB intake when children were aged 5 to 8 years (standardized β= 0.25 [95% CI: 0.10 to 0.40])., Conclusion: Maternal SB consumption during pregnancy is associated with a marginally higher SB intake among their offspring at age 2, and concurrent maternal consumption is associated with a higher SB intake among school-aged offspring (5 to 8 years old). Future interventions tailored for pregnancy and early childrearing years to reduce SB intakes of mothers may reduce young children's SB intake., (© 2022. The Author(s) under exclusive license to The Canadian Public Health Association.)

A systematic competitive evaluation of the DalPhos ligand family in nickel-catalyzed N-arylation chemistry is reported, involving primary (linear and branched) and secondary alkylamines, as well as a primary five-membered heteroarylamine (aminopyrazole), in combination with a diverse set of test electrophiles and bases (NaOtBu, K 2 CO 3 , DBU/NaTFA). In addition to providing optimal ligand/catalyst identification, and bringing to light methodology limitations (e. g., unwanted C-O cross-coupling with NaOtBu), our survey enabled the development of the first efficient catalyst system for heteroatom-dense C-N cross-coupling of aminopyrazoles and related nucleophiles with (hetero)aryl chlorides by use of an amine 'dual-base' system., (© 2022 Wiley-VCH GmbH.)

Chemicals in food are widely used leading to significant human exposure. Allura Red AC (AR) is a highly common synthetic colorant; however, little is known about its impact on colitis. Here, we show chronic exposure of AR at a dose found in commonly consumed dietary products exacerbates experimental models of colitis in mice. While intermittent exposure is more akin to a typical human exposure, intermittent exposure to AR in mice for 12 weeks, does not influence susceptibility to colitis. However, exposure to AR during early life primes mice to heightened susceptibility to colitis. In addition, chronic exposure to AR induces mild colitis, which is associated with elevated colonic serotonin (5-hydroxytryptamine; 5-HT) levels and impairment of the epithelial barrier function via myosin light chain kinase (MLCK). Importantly, chronic exposure to AR does not influence colitis susceptibility in mice lacking tryptophan hydroxylase 1 (TPH1), the rate limiting enzyme for 5-HT biosynthesis. Cecal transfer of the perturbed gut microbiota by AR exposure worsens colitis severity in the recipient germ-free (GF) mice. Furthermore, chronic AR exposure elevates colonic 5-HT levels in naïve GF mice. Though it remains unknown whether AR has similar effects in humans, our study reveals that chronic long-term exposure to a common synthetic colorant promotes experimental colitis via colonic 5-HT in gut microbiota-dependent and -independent pathway in mice., (© 2022. The Author(s).)

Background: While the World Health Organization (WHO) developed postnatal growth standards for infants, corresponding body composition data remains scarce. This study explores growth and body composition trajectories in infants meeting the WHO Multicentre Growth Reference Study (MGRS) eligibility criteria., Study Design: Infants enrolled in this longitudinal cohort underwent anthropometric and body composition measurement by air displacement plethysmography (ADP) at 6 weeks, 12 weeks, and 5 months postnatally. Age and sex-specific growth and body composition percentiles were generated using GAMLSS, with extrapolated data at 5 months for those exceeding ADP weight limits. We evaluated which anthropometric measure (body mass index (BMI), weight for length or mid upper arm circumference) was most closely related to adiposity., Results: Of the 225 infants with body composition measures, 187 met the WHO MGRS criteria. Their length and weight curves were comparable with WHO growth curves. Trajectory curves for fat and fat-free mass were developed. Of the anthropometric measures, BMI z score was most closely related to fat mass index z score at all timepoints., Conclusion: This study presents body composition trajectories for infants meeting the WHO growth standard criteria. BMI z score is the best anthropometric metric to estimate adiposity in infants., Impact: While postnatal growth standards derived from the WHO Multicentre Growth Reference Study (MGRS) exist for the routine clinical assessment of infant growth, this study fills the previous gap in the availability of corresponding body composition data for term-born, healthy, breastfed infants meeting the MGRS criteria. Extrapolation was used to obtain body composition values for infants exceeding the weight limit of the ADP device, to avoid construction of biased body composition curves. Sex-specific growth curves for fat mass, fat-free mass, fat mass index, and fat-free mass index are presented for a population meeting the World Health Organization growth standard criteria., (© 2022. The Author(s), under exclusive licence to the International Pediatric Research Foundation, Inc.)

Objective: To assess stakeholder ratings of health indicators and subgroup analyses in systematic reviews used to update the Canadian Clinical Practice Guideline for Managing Paediatric Obesity., Methods: Stakeholders (caregivers of children with obesity and Clinical Practice Guideline Steering Committee members) completed an online survey between April 2020 and March 2021. Participants rated importance of health indicators and subgroup analyses for behavioural and psychological, pharmacotherapeutic, and surgical interventions for managing paediatric obesity from not important to critically important using Grading, Recommendations, Assessment, Development and Evaluation criteria., Results: No health indicators or subgroup analyses were rated not important by the 30 caregivers and 17 Steering Committee members. Across intervention types, stakeholders rated anxiety, depression, health-related quality of life, serious adverse events, plus age and weight status subgroups as critically important., Conclusion: Stakeholder ratings will inform data reporting and interpretation to update Canada's Clinical Practice Guideline for Managing Paediatric Obesity., (© 2022 World Obesity Federation.)

Diets rich in added sugars are associated with metabolic diseases, and studies have shown a link between these pathologies and changes in the microbiome. Given the reported associations in animal models between the microbiome and brown adipose tissue (BAT) function, and the alterations in the microbiome induced by high-glucose or high-fructose diets, we investigated the potential causal link between high-glucose or -fructose diets and BAT dysfunction in humans. Primary outcomes are changes in BAT cold-induced thermogenesis and the fecal microbiome (clinicaltrials.gov, NCT03188835). We show that BAT glucose uptake, but not thermogenesis, is impaired by a high-fructose but not high-glucose diet, in the absence of changes in the gastrointestinal microbiome. We conclude that decreased BAT glucose metabolism occurs earlier than other pathophysiological abnormalities during fructose overconsumption in humans. This is a potential confounding factor for studies relying on 18 F-FDG to assess BAT thermogenesis., Competing Interests: Declaration of interests A.C.C. received research funding by Eli Lilly (2019–2021) and NovoNordisk (2021–ongoing) and consultation fees by HLS Therapeutics, Janssen Inc., Novartis Pharmaceuticals Canada Inc., and Novo Nordisk Canada Inc. K.M.M. is an advisory board member for NovoNordisk., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Probiotic use in preterm infants can mitigate the impact of antibiotic exposure and reduce rates of certain illnesses; however, the benefit on the gut resistome, the collection of antibiotic resistance genes, requires further investigation. We hypothesized that probiotic supplementation of early preterm infants (born < 32-week gestation) while in hospital reduces the prevalence of antibiotic resistance genes associated with pathogenic bacteria in the gut. We used a targeted capture approach to compare the resistome from stool samples collected at the term corrected age of 40 weeks for two groups of preterm infants (those that routinely received a multi-strain probiotic during hospitalization and those that did not) with samples from full-term infants at 10 days of age to identify if preterm birth or probiotic supplementation impacted the resistome. We also compared the two groups of preterm infants up to 5 months of age to identify persistent antibiotic resistance genes., Results: At the term corrected age, or 10 days of age for the full-term infants, we found over 80 antibiotic resistance genes in the preterm infants that did not receive probiotics that were not identified in either the full-term or probiotic-supplemented preterm infants. More genes associated with antibiotic inactivation mechanisms were identified in preterm infants unexposed to probiotics at this collection time-point compared to the other infants. We further linked these genes to mobile genetic elements and Enterobacteriaceae, which were also abundant in their gut microbiomes. Various genes associated with aminoglycoside and beta-lactam resistance, commonly found in pathogenic bacteria, were retained for up to 5 months in the preterm infants that did not receive probiotics., Conclusions: This pilot survey of preterm infants shows that probiotics administered after preterm birth during hospitalization reduced the diversity and prevented persistence of antibiotic resistance genes in the gut microbiome. The benefits of probiotic use on the microbiome and the resistome should be further explored in larger groups of infants. Due to its high sensitivity and lower sequencing cost, our targeted capture approach can facilitate these surveys to further address the implications of resistance genes persisting into infancy without the need for large-scale metagenomic sequencing. Video Abstract., (© 2022. The Author(s).)

Atherosclerosis begins in youth and is directly linked with the presence and severity of cardiovascular risk factors, including dyslipidemia. Thus, the timely identification and management of dyslipidemia in childhood might slow atherosclerotic progression and decrease the risk of cardiovascular disease in adulthood. This is particularly true for children with genetic disorders resulting in marked dyslipidemia, including familial hypercholesterolemia, which remains frequently undiagnosed. Universal and cascade screening strategies can effectively identify cases of pediatric dyslipidemia. In the clinical evaluation of children with dyslipidemia, evaluating for secondary causes of dyslipidemia, including medications and systemic disorders is essential. The first line therapy generally centres around lifestyle modifications, with dietary changes specific to the dyslipidemia phenotype. Indications for medication depend on the severity of dyslipidemia and an individualized assessment of cardiovascular risk. Despite an expanding evidence base supporting the detection and timely management of pediatric dyslipidemia, numerous knowledge gaps remain, including a sufficient evidence base to support more widespread screening, thresholds for initiation of pharmacotherapy, and treatment targets. Further studies on the most appropriate age for statin initiation and long-term safety studies of statin use in youth are also required. The most pressing matter, however, is the development of knowledge translation strategies to improve the screening and detection of lipid disorders in Canadian youth., (Copyright © 2022 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

Obesogens are synthetic, environmental chemicals that can disrupt endocrine control of metabolism and contribute to the risk of obesity and metabolic disease. Bisphenol A (BPA) is one of the most studied obesogens. There is considerable evidence that BPA exposure is associated with weight gain, increased adiposity, poor blood glucose control, and nonalcoholic fatty liver disease in animal models and human populations. Increased usage of structural analogs of BPA has occurred in response to legislation banning their use in some commercial products. However, BPA analogs may also cause some of the same metabolic impairments because of common mechanisms of action. One key effector that is altered by BPA and its analogs is serotonin, however, it is unknown if BPA-induced changes in peripheral serotonin pathways underlie metabolic perturbations seen with BPA exposure. Upon ingestion, BPA and its analogs act as endocrine-disrupting chemicals in the gastrointestinal tract to influence serotonin production by the gut, where over 95% of serotonin is produced. The purpose of this review is to evaluate how BPA and its analogs alter gut serotonin regulation and then discuss how disruption of serotonergic networks influences host metabolism. We also provide evidence that BPA and its analogs enhance serotonin production in gut enterochromaffin cells. Taken together, we propose that BPA and many BPA analogs represent endocrine-disrupting chemicals that can influence host metabolism through the endogenous production of gut-derived factors, such as serotonin.

Background: Despite the growing number of mobile health (mHealth) interventions targeting childhood obesity, few studies have characterized user typologies derived from individuals' patterns of interactions with specific app features (digital phenotypes)., Objective: This study aims to identify digital phenotypes among 214 parent-child dyads who used the Aim2Be mHealth app as part of a randomized controlled trial conducted between 2019 and 2020, and explores whether participants' characteristics and health outcomes differed across phenotypes., Methods: Latent class analysis was used to identify distinct parent and child phenotypes based on their use of the app's behavioral, gamified, and social features over 3 months. Multinomial logistic regression models were used to assess whether the phenotypes differed by demographic characteristics. Covariate-adjusted mixed-effect models evaluated changes in BMI z scores (zBMI), diet, physical activity, and screen time across phenotypes., Results: Among parents, 5 digital phenotypes were identified: socially engaged (35/214, 16.3%), independently engaged (18/214, 8.4%) (socially and independently engaged parents are those who used mainly the social or the behavioral features of the app, respectively), fully engaged (26/214, 12.1%), partially engaged (32/214, 15%), and unengaged (103/214, 48.1%) users. Married parents were more likely to be fullyengaged than independently engaged (P=.02) or unengaged (P=.01) users. Socially engaged parents were older than fullyengaged (P=.02) and unengaged (P=.01) parents. The latent class analysis revealed 4 phenotypes among children: fully engaged (32/214, 15%), partially engaged (61/214, 28.5%), dabblers (42/214, 19.6%), and unengaged (79/214, 36.9%) users. Fully engaged children were younger than dabblers (P=.04) and unengaged (P=.003) children. Dabblers lived in higher-income households than fully and partiallyengaged children (P=.03 and P=.047, respectively). Fully engaged children were more likely to have fully engaged (P<.001) and partiallyengaged (P<.001) parents than unengaged children. Compared with unengaged children, fully and partiallyengaged children had decreased total sugar (P=.006 and P=.004, respectively) and energy intake (P=.03 and P=.04, respectively) after 3 months of app use. Partially engaged children also had decreased sugary beverage intake compared with unengaged children (P=.03). Similarly, children with fully engaged parents had decreased zBMI, whereas children with unengaged parents had increased zBMI over time (P=.005). Finally, children with independently engaged parents had decreased caloric intake, whereas children with unengaged parents had increased caloric intake over time (P=.02)., Conclusions: Full parent-child engagement is critical for the success of mHealth interventions. Further research is needed to understand program design elements that can affect participants' engagement in supporting behavior change., Trial Registration: ClinicalTrials.gov NCT03651284; https://clinicaltrials.gov/ct2/show/NCT03651284., International Registered Report Identifier (irrid): RR2-10.1186/s13063-020-4080-2., (©Olivia De-Jongh González, Claire N Tugault-Lafleur, E Jean Buckler, Jill Hamilton, Josephine Ho, Annick Buchholz, Katherine M Morrison, Geoff DC Ball, Louise C Mâsse. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 22.06.2022.)

Background: There is a paucity of evidence to support interventions that address the social needs of children and families with chronic medical conditions. The primary objective of this pilot randomized controlled trial (RCT) is to assess the feasibility of an intervention that screens for and addresses the social needs of children and families enrolled in a pediatric weight management clinic., Method: We will conduct a single-center, pilot RCT of 40 families with children enrolled in a pediatric weight management program at a tertiary children's hospital in Ontario, Canada. Families who are experiencing unmet social needs will be randomized to either a community navigator or self-navigation of community resources. The primary feasibility outcomes and criteria for success include the following: (1) recruitment rates, will be successful if 80% of our target sample is met in the 6 months of recruitment; (2) uptake of intervention, will be considered successful if > 80% of families complete the intervention; and (3) follow-up of participants, will be considered successful if > 90% of participants complete all the study visits. The secondary outcomes include estimating the preliminary effects on body mass index, body composition, and quality of life at 6 months. The analysis of feasibility outcomes will be based on descriptive statistics, and analysis of secondary clinical outcomes will be reported as estimates of effect. We will not perform tests of significance since these analyses are purely exploratory., Discussion: This study is important because it will aim to improve the treatment of pediatric obesity by testing the feasibility of an intervention that addresses unmet social needs., Trial Registration: ClinicalTrias.gov : NCT04711707 (Registered January 13, 2021)., (© 2022. The Author(s).)

The extent to which variation in food-related metabolites are attributable to non-dietary factors remains unclear, which may explain inconsistent food-metabolite associations observed in population studies. This study examined the association between non-dietary factors and the serum concentrations of food-related biomarkers and quantified the amount of variability in metabolite concentrations explained by non-dietary factors. Pregnant women ( n = 600) from two Canadian birth cohorts completed a validated semi-quantitative food frequency questionnaire, and serum metabolites were measured by multisegment injection-capillary electrophoresis-mass spectrometry. Hierarchical linear modelling and principal component partial R-square (PC-PR2) were used for data analysis. For proline betaine and DHA (mainly exogenous), citrus foods and fish/fish oil intake, respectively, explained the highest proportion of variability relative to non-dietary factors. The unique contribution of dietary factors was similar (15:0, 17:0, hippuric acid, TMAO) or lower (14:0, tryptophan betaine, 3-methylhistidine, carnitine) compared to non-dietary factors (i.e., ethnicity, maternal age, gestational age, pre-pregnancy BMI, physical activity, and smoking) for metabolites that can either be produced endogenously, biotransformed by gut microbiota, and/or derived from multiple food sources. The results emphasize the importance of adjusting for non-dietary factors in future analyses to improve the accuracy and precision of the measures of food intake and their associations with health and disease.

Childhood obesity is a growing worldwide problem. In adults, lower cold-induced brown adipose tissue (BAT) activity is linked to obesity and metabolic dysfunction; this relationship remains uncertain in children. In this cross-sectional study, we compared cold-induced supraclavicular (SCV) BAT activity (percent change in proton density fat fraction [PDFF]) within the SCV region after 1 h of whole-body cold exposure (18°C), using MRI in 26 boys aged 8-10 years: 13 with normal BMI and 13 with overweight/obesity. Anthropometry, body composition, hepatic fat, visceral adipose tissue (VAT), and pre- and postcold PDFF of the subcutaneous adipose tissue (SAT) in the posterior neck region and the abdomen were measured. Boys with overweight/obesity had lower cold-induced percent decline in SCV PDFF compared with those with normal BMI (1.6 ± 0.8 vs. 4.7 ± 1.2%, P = 0.044). SCV PDFF declined significantly in boys with normal BMI (2.7 ± 0.7%, P = 0.003) but not in boys with overweight/obesity (1.1 ± 0.5%, P = 0.053). No cold-induced changes in the PDFF of either neck SAT (-0.89 ± 0.7%, P = 0.250, vs. 0.37 ± 0.3%, P = 0.230) or abdominal SAT (-0.39 ± 0.5%, P = 0.409, and 0.25 ± 0.2%, P = 0.139, for normal BMI and overweight/obesity groups, respectively) were seen. The cold-induced percent decline in SCV PDFF was inversely related to BMI (r = -0.39, P = 0.047), waist circumference (r = -0.48, P = 0.014), and VAT (r = -0.47, P = 0.014). Thus, in young boys, as in adults, BAT activity is lower in those with overweight/obesity, suggesting that restoring activity may be important for improving metabolic health., (© 2022 by the American Diabetes Association.)