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Background: Prepubertal children with obesity frequently have enhanced growth, accelerated skeletal maturation, and changes in the growth hormone-insulin-like growth factor (GH-IGF) axis. However, the involvement of pappalysins (PAPP-A, PAPP-A2) and stanniocalcins (STC1, STC2) as regulators of IGF bioavailability has not been studied in obesity., Objective: We aimed to determine the effects of childhood obesity and weight reduction on serum levels of PAPP-A, PAPP-A2, STC1, and STC2 and their relationship with IGF bioavailability, growth, and other components of the GH-IGF system., Methods: Prepubertal children with severe obesity (150, 50% males/females, age: 7.72 ± 2.05 years, BMI z-score: 4.95 ± 1.70, height z-score: 1.28 ± 1.04) were studied at diagnosis and after a minimum of 0.5 BMI z-score reduction. Two hundred and six healthy age- and sex-matched children were used as controls., Results: Children with obesity had decreased serum concentrations of PAPP-A, PAPP-A2 and STC2, but increased total and free IGF-I, intact IGFBP-3, acid-labile subunit (ALS), IGF-II, and insulin levels, with no difference in the free IGF-I/total IGF-I ratio. Neither the standardized body mass index (BMI) nor height correlated with any biochemical parameter analyzed. A decrease in IGF-II, insulin, and ALS with an increase in IGFBP-2 and -5, STC2, and PAPP-A were observed after weight loss., Conclusion: Increased circulating total and free IGF-I, insulin, and IGF-II may all contribute to the increased rate of prepubertal growth and bone maturation observed in children with obesity, with STC2 possibly being involved., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Introduction: The pathophysiology of cardiovascular diseases encompasses a complex interplay of genetic and environmental risk factors. Even if traditional risk factors are treated to target, there remains a residual risk., Areas Covered: This manuscript reviews the potential role of gut microbiota in the development of cardiovascular disease, and as potential target. A systematic search was conducted until 30 October 2024 on PubMed (MEDLINE), using the MeSH terms [Gut microbiota] + [Dysbiosis] + [Cardiovascular] + [TMAO] + [bile acids] + [short-chain fatty acids]., Expert Opinion: The term dysbiosis implies changes in equilibrium, with modifications in the composition and functionality of microbiota and a series of additional factors: reduced diversity and uniformity of microorganisms; reduced short-chain fatty acid-producing bacteria; increased gut permeability; release of metabolites, such as trimethylamine N-oxide, betaine, phenylalanine, tryptophan-kynurenine, phenylacetylglutamine, and lipopolysaccharides; and reduced secondary bile acid excretion, leading to inflammation, oxidative stress, and endothelial dysfunction and facilitating the onset of pathological conditions, including obesity, hypertension, diabetes, atherosclerosis, and heart failure. Attempts to restore gut microbiota balance through different interventions, mainly changes in diet, have been shown to positively affect individual components and metabolites and reduce the risk of cardiovascular disease. In addition, probiotics and prebiotics are potentially useful. Fecal microbiota transplantation is a promising therapy.

Freshwater ecosystems are highly biodiverse 1 and important for livelihoods and economic development 2 , but are under substantial stress 3 . To date, comprehensive global assessments of extinction risk have not included any speciose groups primarily living in freshwaters. Consequently, data from predominantly terrestrial tetrapods 4,5 are used to guide environmental policy 6 and conservation prioritization 7 , whereas recent proposals for target setting in freshwaters use abiotic factors 8-13 . However, there is evidence 14-17 that such data are insufficient to represent the needs of freshwater species and achieve biodiversity goals 18,19 . Here we present the results of a multi-taxon global freshwater fauna assessment for The IUCN Red List of Threatened Species covering 23,496 decapod crustaceans, fishes and odonates, finding that one-quarter are threatened with extinction. Prevalent threats include pollution, dams and water extraction, agriculture and invasive species, with overharvesting also driving extinctions. We also examined the degree of surrogacy of both threatened tetrapods and freshwater abiotic factors (water stress and nitrogen) for threatened freshwater species. Threatened tetrapods are good surrogates when prioritizing sites to maximize rarity-weighted richness, but poorer when prioritizing based on the most range-restricted species. However, they are much better surrogates than abiotic factors, which perform worse than random. Thus, although global priority regions identified for tetrapod conservation are broadly reflective of those for freshwater faunas, given differences in key threats and habitats, meeting the needs of tetrapods cannot be assumed sufficient to conserve freshwater species at local scales., Competing Interests: Competing interests: G.R., M.L. and L.M.-T. are affiliated with commercial companies (Elimia, Fish Fondler Pty Ltd. and Mott MacDonald, respectively), but their contributions to this paper were made in a voluntary capacity. The other authors declare no competing interests., (© 2025. The Author(s).)