Search

A multidisciplinary group of experts gathered in Parma Italy for a workshop hosted by the University of Parma, May 16-18, 2014 to address concerns about the potential relationship between environmental metabolic disrupting chemicals, obesity and related metabolic disorders. The objectives of the workshop were to: 1. Review findings related to the role of environmental chemicals, referred to as "metabolic disruptors", in obesity and metabolic syndrome with special attention to recent discoveries from animal model and epidemiology studies; 2. Identify conclusions that could be drawn with confidence from existing animal and human data; 3. Develop predictions based on current data; and 4. Identify critical knowledge gaps and areas of uncertainty. The consensus statements are intended to aid in expanding understanding of the role of metabolic disruptors in the obesity and metabolic disease epidemics, to move the field forward by assessing the current state of the science and to identify research needs on the role of environmental chemical exposures in these diseases. We propose broadening the definition of obesogens to that of metabolic disruptors, to encompass chemicals that play a role in altered susceptibility to obesity, diabetes and related metabolic disorders including metabolic syndrome.

Aims: To compare two strategies for the eradication of Helicobacter pylori infection.Methods: Groups 1 and 2 each consisted of 75 consecutive patients. Patients in group 1 were treated with two antibiotics based on antibiotic susceptibility testing; those in group 2 received amoxycillin and clarithromycin for eight days, together with either ranitidine or omeprazole. Eradication rate was assessed in both groups six months after treatment.Results: In group 1, H pylori grew in culture in 63/75 cases. Susceptibility testing showed that 35/63 isolates were resistant to metronidazole, 10/63 to clarithromycin, 2/63 to ampicillin, 1/63 to tetracycline, and 5/63 to both clarithromycin and metronidazole. In group 1 the infection was eradicated in 96% of the initial 75 subjects, and in 98% of the subjects treated according to the antibiotic assay (62/63). As two patients were lost at follow up the overall eradication rate was 99%. In group 2, eradication was achieved in 61/75 subjects (81%). This was significantly lower than the percentage of eradication observed in group 1 (81% versus 99%).Conclusions: Antibiotic susceptibility tests are useful in childhood as a very high percentage of subjects are cured. This approach is costly, but selective antibiotic treatment contributes to limit further development of antibiotic resistance, and money is saved in terms of reinvestigation and further repeated treatments. [ABSTRACT FROM AUTHOR]

Background: Changes and relationships of components of the cytokine and IGF systems have been shown in placenta and cord serum of fetal growth restricted (FGR) compared with normal newborns (AGA). This study aimed to analyse a data set of clinical and biochemical data in FGR and AGA newborns to assess if a mathematical model existed and was capable of identifying these two different conditions in order to identify the variables which had a mathematically consistent biological relevance to fetal growth.Methods: Whole villous tissue was collected at birth from FGR (N = 20) and AGA neonates (N = 28). Total RNA was extracted, reverse transcribed and then real-time quantitative (TaqMan) RT-PCR was performed to quantify cDNA for IGF-I, IGF-II, IGFBP-1, IGFBP-2 and IL-6. The corresponding proteins with TNF-alpha in addition were assayed in placental lysates using specific kits. The data were analysed using Artificial Neural Networks (supervised networks), and principal component analysis and connectivity map.Results: The IGF system and IL-6 allowed to predict FGR in approximately 92% of the cases and AGA in 85% of the cases with a low number of errors. IGF-II, IGFBP-2, and IL-6 content in the placental lysates were the most important factors connected with FGR. The condition of being FGR was connected mainly with the IGF-II placental content, and the latter with IL-6 and IGFBP-2 concentrations in placental lysates.Conclusion: These results suggest that further research in humans should focus on these biochemical data. Furthermore, this study offered a critical revision of previous studies. The understanding of this system biology is relevant to the development of future therapeutical interventions possibly aiming at reducing IL-6 and IGFBP-2 concentrations preserving IGF bioactivity in both placenta and fetus. [ABSTRACT FROM AUTHOR]

Context: There has been concern about a potential increase in the incidence or severity of Coronavirus Disease 2019 (COVID-19) in individuals with adrenal insufficiency (AI). Data on the course of SARS-CoV-2 infection in AI children are lacking., Objective: Evaluate whether children with AI are more susceptible to the infection or are at risk of severe COVID-19., Patients: 1143 children with AI. Of these, 148 patients, 112 with primary (PAI) and 36 with secondary AI (SAI), and 74 control subjects with normal adrenal function, who contracted SARS-CoV-2, were evaluated for the severity and outcomes of infection., Design: Multicenter, retrospective., Results: The prevalence of COVID-19 in AI cohort was 12.9%, not increased compared to pediatric Italian population in the same period. The severity was not increased in AI subjects and was classified as follows in patients vs controls: asymptomatic in 14.9 vs 10.8 %; paucisymptomatic in 33.8 vs 37.8 %; mild in 45.3 vs 45.9 %; severe in 3.4 vs 2.7%; critical in 2.7 vs 2.7%. Among those with severe COVID, 4 patients with AI (2.7%) and 3 controls (4%) developed pneumonia while 3 patients with PAI (2%) and 2 controls (2.7%) developed MIS-C (p=ns). Only 5 patients (3.4%) experienced an adrenal crisis during a severe COVID-19. Hospitalization rate was the same in patients vs controls (9.5%). All subjects completely recovered and no COVID-related deaths were documented., Conclusions: Our findings do not indicate that AI is associated with increased susceptibility to SARS-CoV-2 infection or higher risk for severe COVID-19 in children., (© The Author(s) 2025. Published by Oxford University Press on behalf of the Endocrine Society.)

Background: The aim of the study was to explore a radiomic model that could assist physicians in the diagnosis of central precocious puberty (CPP). A predictive model based on radiomic features (RFs), extracted form magnetic resonance imaging (MRI) of the pituitary gland, was thus developed to distinguish between CPP and control subjects., Methods: 45 girls with confirmed diagnosis of CPP (CA:8.4 ± 0.9 yr) according to the current criteria and 47 age-matched pre-pubertal control subjects (CA:8.7 ± 1.2 yr) were retrospectively enrolled. Two readers (R1, R2) blindly segmented the pituitary gland on MRI studies for RFs and performed a manual estimation of the pituitary volume. Radiomics was compared against pituitary volume in terms of predictive performances (metrics: ROC-AUC, accuracy, sensitivity and specificity) and reliability (metric: intraclass correlation coefficient, ICC). Pearson correlation between RFs and auxological, biochemical, and ultrasound data was also computed., Results: Two different radiomic parameters, Shape Surface Volume Ratio and Glrlm Gray Level Non-Uniformity, predicted CPP with a high diagnostic accuracy (ROC-AUC 0.81 ± 0.08) through the application of our ML algorithm. Anthropometric variables were not confounding factors of these RFs suggesting that premature thelarche and/or pubarche would not be potentially misclassified. The selected RFs correlated with baseline and peak LH (p < 0.05) after GnRH stimulation. The diagnostic sensitivity was improved compared to pituitary volume only (0.76 versus 0.68, p<0.001) and demonstrated higher inter-reader reliability (ICC>0.57 versus ICC=0.46)., Discussion: Radiomics is a promising tool to diagnose CPP as it reflects also functional aspects. Further studies are warranted to validate these preliminary data., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2025 Maddalo, Petraroli, Ormitti, Fulgoni, Gnocchi, Masetti, Borgia, Piccolo, Turco, Patianna, Sverzellati, Esposito, Ghetti and Street.)

Breast milk (BM) is the main nutrition source for infants that plays a key role on growth and development. Human milk composition includes endogenous and exogenous substances, including endocrine disrupting chemicals (EDCs). EDCs are man-made environmental chemicals present in everyday environment and food that can disrupt the programming of endocrine signalling pathways during development, resulting in adverse effects that may not be apparent until much later in life. The presence of single and/or mixtures of EDCs in BM has been shown to be associated with impairment of reproductive, metabolic, immunologic system and neurobehavioral developmental outcomes. This systematic review discusses the current knowledge about the presence of EDCs in BM, and their potential effects on infant outcomes during the first six years of life. Following PRISMA guidelines, we made a systematic evaluation of the literature on the effects of single and mixtures EDC on (i) mental and psychomotor development; (ii) socio-communicative and behavioral development. Negative association between EDC exposure and developmental areas considered emerged highlighting: (i) BM as a potential key matrix for the monitoring of EDC exposure (ii) the short- and long-term negative effect on infant neuro-behavioral outcomes, and (iii) the importance of public health efforts to reduce maternal and infant EDC exposure. However, heterogeneous results found emphasizes the need to further longitudinal studies to consider factors that can lower EDC exposure or exert a protective role on infant neurodevelopment, and to better understand the mechanism behind the EDCs and its effects on infant development., Competing Interests: Declaration of Competing interests The authors declare no competing interest to the authorship and/or publication of this paper., (Copyright © 2025 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Purpose: Puberty is a key phase of growth and development, characterized by psychophysical transformations. It is driven by a combination of genetic, hormonal, and environmental variables. Epigenetic mechanisms, including histone post-translational modifications and chromatin remodeling, microRNAs, and DNA methylation, play important roles in orchestrating the developmental processes. We describe environmental factors that may interact with genetics, and factors influencing puberty onset, focusing in particular on epigenetic mechanisms that can help understand the timing and variations that lead to precocious or delayed puberty., Methods: We conducted a narrative review of associations between puberty and epigenetic mechanisms through a comprehensive search of PubMed, Scopus, and Web of Science databases., Results: The chromatin landscape of genes as KISS1 has revealed dynamic changes in histone modifications as puberty approaches, influencing the stimulation or inhibition of gene expression critical for reproductive maturation. MiRNAs regulate gene expression, whereas DNA methylation affects activation or repression of gene transcription of genes involved in pubertal timing. Moreover, studies in animal models have provided insights into the role of DNA methylation and miRNAs in brain sexual differentiation, highlighting the active involvement of epigenetic mechanisms in shaping sexually dimorphic brain structures., Conclusion: This review highlights the importance of understanding the complex interplay between epigenetic regulation and pubertal development, which can lead to new therapeutic options and shed light on the fundamental processes driving reproductive maturation., Competing Interests: Declarations. Conflict of interest: The authors have no conflicts of interest relevant to this article to disclose. Ethical approval: No approval needed. Research involving human participants and/or animals: No patient/animal was involved in the present research. Informed consent: For this type of study, formal consent is not required., (© 2024. The Author(s).)

Telemedicine (TM) has emerged as a valuable tool in managing pediatric type 1 diabetes (T1D), particularly during the COVID-19 pandemic when traditional in-person visits were limited. This narrative review examines the impact of TM on patient-provider relationships, glycemic control, and overall diabetes management in children and adolescents with T1D. Studies consistently demonstrate high levels of patient and provider satisfaction with TM, citing increased consultation frequency, reduced travel burdens, and lower associated costs. However, results regarding the effect of TM on glycemic control, as measured by HbA1c levels, are inconsistent. Some studies show significant reductions in HbA1c levels with TM use, while others report outcomes comparable to or less effective than traditional care. The effectiveness of TM also appears to be influenced by the concurrent use of advanced diabetes technologies, such as continuous glucose monitors and automated insulin delivery systems. Furthermore, TM's impact on quality of life and other clinical outcomes beyond glucose management remains underexplored. Methodological limitations, including inconsistent randomization strategies and lack of long-term follow-up, hinder definitive conclusions. Despite these uncertainties, TM offers several advantages, such as improved accessibility and patient engagement, which may justify its broader implementation. Future research should focus on optimizing TM approaches to enhance glycemic control and quality of life, identifying the most effective strategies for specific patient groups, and addressing technological and economic barriers. This review highlights the need for comprehensive, long-term studies to fully understand TM's potential in pediatric T1D management and its integration into standard care practices., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Esposito, Sambati, Fogliazza, Street and Principi.)

The COVID-19 pandemic has catalyzed the rapid expansion of telemedicine for managing chronic conditions such as type 1 diabetes (T1D) in children and adolescents. This narrative review aims to explore the role of telemedicine in pediatric T1D management by comparing its use before and after the pandemic. We conducted a comprehensive literature review covering studies published between 2000 and 2024, focusing on telemedicine applications in pediatric T1D care. The review includes clinical trials, systematic reviews, and observational studies examining telemedicine's impact on glycemic control, patient satisfaction, and healthcare delivery. Results reveal that telemedicine has enhanced access to care, improved glycated hemoglobin (HbA1c) levels, and reduced diabetic ketoacidosis and hypoglycemic events. Patients and caregivers expressed high satisfaction, especially when using continuous glucose monitoring and insulin pump technologies integrated with telemedicine platforms. However, challenges such as digital literacy gaps, variability in healthcare provider training, and logistical issues like reimbursement policies persist. The pandemic highlighted the potential of telemedicine to supplement traditional in-person care, showing promise in enhancing patient outcomes and reducing healthcare burdens. Further research is needed to optimize telemedicine models for T1D, addressing barriers to implementation and exploring its long-term cost-effectiveness. This review underscores telemedicine's evolving role as a complementary approach in managing pediatric T1D, advocating for the development of standardized care protocols to fully integrate digital health solutions into routine clinical practice.

Purpose: Omnitrope ® (a somatropin biosimilar), used to treat growth disturbances, is considered to have a good safety profile in children. Here, we present the analysis of final data of the Italian cohort of the PAtients TReated with Omnitrope ® (PATRO) Children study., Methods: This multicenter, open-label, longitudinal, post-marketing surveillance study enrolled eligible children during 2010-2018. The primary objective was to assess the long-term safety of Omnitrope ® by recording all adverse events (AEs), serious AEs, and adverse drug reactions (ADRs). A secondary objective was to evaluate the long-term effectiveness of Omnitrope ® using height measurements., Results: A total of 375 patients were included in the Italian cohort of the PATRO Children study. After a mean ± standard deviation (SD) follow-up duration of 40.9 ± 24.6 months, 607 AEs were reported in 58.4% of patients, mostly of mild (52.5%) or moderate (15.7%) severity. The most common AEs were headache (11.7%), elevated insulin-like growth factor (IGF)-1 (4.8%), abdominal pain (4.3%), and pyrexia (3.7%). Sixty-seven ADRs occurred in 52 patients (13.9%); the most common ADRs were elevated IGF-1 (3.5%) and insulin resistance (2.9%). Mean ± SD height standard deviation scores in treatment-naïve patients increased from -2.5 ± 0.7 at baseline (n = 318) to -1.3 ± 0.7 at 5 years (n = 56) and to -0.8 ± 0.7 at 7.5 years (n = 13)., Conclusions: This final analysis extends the interim analysis findings from the PATRO Children study and confirms the long-term safety and effectiveness of Omnitrope ® in Italian pediatric patients with growth disturbances., Competing Interests: Compliance with ethical standards. Conflict of interest: Lorenzo Iughetti has received fees for participation on advisory boards from Sandoz. Franco Antoniazzi has received research funding from Merck Serono and Sandoz, and fees for participation on advisory boards from BioMarin. Tommaso Aversa has consulted for Pfizer and Sandoz. Luca Persani has received fees for participation on advisory boards from Sandoz. Gabriella Pozzobon has received consulting fees and for participation on advisory boards from Sandoz, Merck Serono and Novo Nordisk. Emiliano Zecchi, Paolo Fedeli and Markus Zabransky are part of Sandoz Company Organization. Claudia Giavoli, Simonetta Bellone, Laura Guazzarotti, Maria Elisabeth Street, Emanuele Miraglia del Giudice, Stefano Stagi, Gianluca Tornese, Chiara Mameli, Laura Lucaccioni, Letizia Ragusa, Clara Zecchino, and Stefano Zucchini have no relevant financial or non-financial interests to disclose. Ethics approval: The study was reviewed and approved by each study site’s Independent Ethics Committee/Institutional Review Board. Research involving human participants: All procedures performed in this study involving human participants were in accordance with the ethical standards of the institutional and/or national research committees, with the 1964 Helsinki Declaration and its later amendments, and with the ethical principles outlined in the Oviedo Human Rights Convention. Consent to participate: All patients (or their parents/legal guardians) provided written informed consent before study inclusion., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Exposure to endocrine-disrupting chemicals (EDCs) is inevitable, and growing scientific evidence indicates that even very low doses can negatively impact human health, particularly during pregnancy and the neonatal period. As part of the European project LIFE18 ENV/IT/00460, this study aims to identify the presence of EDCs in 20 infant formulas (both powdered and liquid) and the release from baby bottles and teats. Particularly, sensitization of young people and future parents towards the potential harmful effects of EDCs could significantly help to reduce exposure. Seven different UPLC-MS/MS methodologies and one ICP-AES were set up to quantify already assessed and suspected EDCs among 85 different chemicals (bisphenols, parabens, PAHs, phthalates, pesticides, herbicides and their main metabolites, PFAS, and metals). Results showed that in 2 out of 14 baby bottles, only anthracene and phenanthrene of the group of PAHs were released (10.68-10.81 ng/mL). Phthalates such as mono-ethyl phthalate (MEP) were found in 9 of 14 samples (0.054-0.140 ng/mL), while mono(2-ethyl-5-oxohexyl) phthalate (MeOHP) appeared in 2 samples (0.870-0.930 ng/mL). In accordance with current EU regulations, other chemicals were not detected in baby bottles and teats. However, bisphenols, parabens, PAHs, phthalates, PFAS, and metals were detected in infant formula, emphasizing the need for continued monitoring and public health interventions.

Despite the implementation of preventive measures to counteract the obesity epidemics, the prevalence of childhood obesity is still alarming all over the world. Childhood obesity is the most common risk factor for both cardiovascular and metabolic diseases. In fact, an earlier onset of obesity can cause a greater risk of adiposity tracking across the lifespan and consequently a longer exposure to cardiometabolic risk factors. Accumulating evidence provided by prospective and intervention studies demonstrated the link between pediatric obesity and selected subclinical signs of cardiovascular damage (atherosclerosis and left ventricular hypertrophy), or fatal and not fatal cardiovascular events as early as 40 years of age.The numerous guidelines and scientific documents published in the last years demonstrate the relevance of assessing cardiometabolic risk factors in children and adolescents with OB.This Position paper, released by experts of the "Childhood Obesity study group" within the Italian Society for Pediatric Endocrinology and Diabetology, aims to review the assessment of cardiometabolic risk factors and comorbidities in children and adolescents with OW/OB on the light of the most recent scientific evidence.The main recommendations are: (a) early detection of comorbidities, including hypertension, dyslipidemia, prediabetes/type 2 diabetes, metabolic dysfunction-associated steatotic liver disease, polycystic ovary syndrome, inactivity, obstructive sleep apnea and decline in kidney function; (b) weight loss treatment, which is associated with a reduction of all cardiometabolic risk factors; (c) specific treatment of comorbidities, through lifestyle modifications or pharmacological treatment added to lifestyle for suitable individuals; d). monitoring comorbidities for mitigating future morbidity and mortality., (© 2024. The Author(s).)

The increase in female reproductive disorders, such as polycystic ovary syndrome, endometriosis, and diminished ovarian reserve that lead to subfertility and infertility, has encouraged researchers to search and discover their underlying causes and risk factors. One of the crucial factors that may influence the increasing number of reproductive issues is environmental pollution, particularly exposure to man-made endocrine-disrupting chemicals (EDCs). EDCs can interfere with the ovarian microenvironment, impacting not only granulosa cell function but also other surrounding ovarian cells and follicular fluid (FF), which all play essential roles for oocyte development, maturation, and overall reproductive function. FF surrounds developing oocytes within an ovarian follicle and represents a dynamic milieu. EDCs are usually found in biological fluids, and FF is therefore of interest in this respect. This narrative review examines the current knowledge on specific classes of EDCs, including industrial chemicals, pesticides, and plasticizers, and their known effects on hormonal signaling pathways, gene expression, mitochondrial function, oxidative stress induction, and inflammation in FF. We describe the impact of EDCs on the development of reproductive disorders, oocyte quality, menstrual cycle regulation, and their effect on assisted reproductive technique outcomes. The potential transgenerational effects of EDCs on offspring through animal and first-human studies has been considered also. While significant progress has been made, the current understanding of EDCs' effects on ovarian function, particularly in humans, remains limited, underscoring the need for further research to clarify actions and effects of EDCs in the ovary., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Shulhai, Bianco, Donini, Esposito and Street.)

The incidence of osteoporosis in children is increasing because of the increased survival rate of children with chronic diseases and the increased use of bone-damaging drugs. As childhood bone fragility has several etiologies, its management requires a thorough evaluation of all potentially contributing pathogenetic mechanisms. This review focuses on the main causes of primary and secondary osteoporosis and on the benefits and limits of the different radiological methods currently used in clinical practice for the study of bone quality. The therapeutic and preventive strategies currently available and the most novel diagnostic and treatment strategies are also presented. Optimal management of underlying systemic conditions is key for the treatment of bone fragility in childhood. DXA still represents the gold standard for the radiologic evaluation of bone health in children, although other imaging techniques such as computed tomography and ultrasound evaluations, as well as REMS, are increasingly studied and used. Bisphosphonate therapy is the gold standard for pharmacological treatment in both primary and secondary pediatric osteoporosis. Evidence and experience are building up relative to the use of monoclonal antibodies such as denosumab in cases of poor response to bisphosphonates in specific conditions such as osteogenesis imperfecta, juvenile Paget's disease and in some cases of secondary osteoporosis. Lifestyle interventions including adequate nutrition with adequate calcium and vitamin D intake, as well as physical activity, are recommended for prevention.

Thyroid function is closely linked to nutrition through the diet-gut-thyroid axis. This narrative review highlights the influence of nutritional components and micronutrients on thyroid development and function, as well as on the gut microbiota. Micronutrients such as iodine, selenium, iron, zinc, copper, magnesium, vitamin A, and vitamin B12 influence thyroid hormone synthesis and regulation throughout life. Dietary changes can alter the gut microbiota, leading not just to dysbiosis and micronutrient deficiency but also to changes in thyroid function through immunological regulation, nutrient absorption, and epigenetic changes. Nutritional imbalance can lead to thyroid dysfunction and/or disorders, such as hypothyroidism and hyperthyroidism, and possibly contribute to autoimmune thyroid diseases and thyroid cancer, yet controversial issues. Understanding these relationships is important to rationalize a balanced diet rich in essential micronutrients for maintaining thyroid health and preventing thyroid-related diseases. The synthetic comprehensive overview of current knowledge shows the importance of micronutrients and gut microbiota for thyroid function and uncovers potential gaps that require further investigation.

The thyroid gland regulates most of the physiological processes. Environmental factors, including climate change, pollution, nutritional changes, and exposure to chemicals, have been recognized to impact thyroid function and health. Thyroid disorders and cancer have increased in the last decade, the latter increasing by 1.1% annually, suggesting that environmental contaminants must play a role. This narrative review explores current knowledge on the relationships among environmental factors and thyroid gland anatomy and function, reporting recent data, mechanisms, and gaps through which environmental factors act. Global warming changes thyroid function, and living in both iodine-poor areas and volcanic regions can represent a threat to thyroid function and can favor cancers because of low iodine intake and exposure to heavy metals and radon. Areas with high nitrate and nitrite concentrations in water and soil also negatively affect thyroid function. Air pollution, particularly particulate matter in outdoor air, can worsen thyroid function and can be carcinogenic. Environmental exposure to endocrine-disrupting chemicals can alter thyroid function in many ways, as some chemicals can mimic and/or disrupt thyroid hormone synthesis, release, and action on target tissues, such as bisphenols, phthalates, perchlorate, and per- and poly-fluoroalkyl substances. When discussing diet and nutrition, there is recent evidence of microbiome-associated changes, and an elevated consumption of animal fat would be associated with an increased production of thyroid autoantibodies. There is some evidence of negative effects of microplastics. Finally, infectious diseases can significantly affect thyroid function; recently, lessons have been learned from the SARS-CoV-2 pandemic. Understanding how environmental factors and contaminants influence thyroid function is crucial for developing preventive strategies and policies to guarantee appropriate development and healthy metabolism in the new generations and for preventing thyroid disease and cancer in adults and the elderly. However, there are many gaps in understanding that warrant further research., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Street, Shulhai, Petraroli, Patianna, Donini, Giudice, Gnocchi, Masetti, Montani, Rotondo, Bernasconi, Iughetti, Esposito and Predieri.)

Prader-Willi syndrome (PWS) is a complex genetic disorder caused by three different types of molecular genetic abnormalities. The most common defect is a deletion on the paternal 15q11-q13 chromosome, which is seen in about 60% of individuals. The next most common abnormality is maternal disomy 15, found in around 35% of cases, and a defect in the imprinting center that controls the activity of certain genes on chromosome 15, seen in 1-3% of cases. Individuals with PWS typically experience issues with the hypothalamic-pituitary axis, leading to excessive hunger (hyperphagia), severe obesity, various endocrine disorders, and intellectual disability. Differences in physical and behavioral characteristics between patients with PWS due to deletion versus those with maternal disomy are discussed in literature. Patients with maternal disomy tend to have more frequent neurodevelopmental problems, such as autistic traits and behavioral issues, and generally have higher IQ levels compared to those with deletion of the critical PWS region. This has led us to review the pertinent literature to investigate the possibility of establishing connections between the genetic abnormalities and the endocrine disorders experienced by PWS patients, in order to develop more targeted diagnostic and treatment protocols. In this review, we will review the current state of clinical studies focusing on endocrine disorders in individuals with PWS patients, with a specific focus on the various genetic causes. We will look at topics such as neonatal anthropometry, thyroid issues, adrenal problems, hypogonadism, bone metabolism abnormalities, metabolic syndrome resulting from severe obesity caused by hyperphagia, deficiencies in the GH/IGF-1 axis, and the corresponding responses to treatment., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Madeo, Zagaroli, Vandelli, Calcaterra, Crinò, De Sanctis, Faienza, Fintini, Guazzarotti, Licenziati, Mozzillo, Pajno, Scarano, Street, Wasniewska, Bocchini, Bucolo, Buganza, Chiarito, Corica, Di Candia, Francavilla, Fratangeli, Improda, Morabito, Mozzato, Rossi, Schiavariello, Farello, Iughetti, Salpietro, Salvatoni, Giordano, Grugni and Delvecchio.)

Purpose: PCOS is associated with low grade inflammation which could play a role in insulin resistance and ovarian dysfunction. Preliminary findings suggested that serum levels of HMGB1, a cytokine involved in inflammation, might be altered in women with PCOS. Primary aim of this study was to assess whether HMGB1 serum concentrations are associated with PCOS and with the state of insulin resistance of these women., Methods: Sixty women with PCOS, selected to have a similar proportion of subjects with altered or normal insulin sensitivity, and 29 healthy controls were studied. Serum HMGB1 levels were compared in subgroups of PCOS women and controls. In PCOS women, insulin sensitivity was assessed by the glucose clamp technique and HMGB1 was measured at baseline and after acute hyperinsulinemia., Results: HMGB1 levels were similar in women with PCOS and controls and no elements used for diagnosing PCOS were associated with serum HMGB1. However, HMGB1 concentrations were higher in insulin-resistant vs insulin-sensitive PCOS women (p = 0.017), and inversely associated with insulin-induced total and non-oxidative glucose metabolism. In both subgroups of PCOS women, serum HMBG1 levels significantly increased after acute hyperinsulinemia., Conclusions: These data suggest that HMGB1 levels are not associated with PCOS per se, but with insulin resistance. Further research should establish the underlying nature of this relationship, and whether this protein might play a role in the metabolic complications of PCOS., (© 2023. The Author(s).)

Oxytocin (OT) is a neurohypophyseal peptide hormone containing a disulphide-bridged pseudocyclic conformation. The biomedical use of OT peptides is limited amongst others by disadvantageous pharmacokinetic parameters. To increase the stability of OT by replacing the disulphide bridge with the stable and more rigid [1,2,3]triazol-1-yl moiety, we employed the Cu 2+ -catalysed side chain-to-side chain azide-alkyne 1,3-cycloaddition. Here we report the design, synthesis, conformational analysis, and in vitro pharmacological activity of a homologous series of Cα 1 -to-Cα 6 side chain-to-side chain [1,2,3]triazol-1-yl-containing OT analogues differing in the length of the bridge, location, and orientation of the linking moiety. Exploiting this macrocyclisation approach, it was possible to generate a systematic series of compounds providing interesting insight into the structure-conformation-function relationship of OT. Most analogues were able to adopt similar conformation to endogenous OT in water, namely, a type I β-turn. This approach may in the future generate stabilised pharmacological peptide tools to advance understanding of OT physiology.

Bone health starts with maternal health and nutrition, which influences bone mass and density already in utero. The mechanisms underlying the effect of the intrauterine environment on bone health are partly unknown but certainly include the 'foetal programming' of oxidative stress and endocrine systems, which influence later skeletal growth and development. With this narrative review, we describe the current evidence for identifying patients with risk factors for developing osteopenia, today's management of these populations, and screening and prevention programs based on gestational age, weight, and morbidity. Challenges for bone health prevention include the need for new technologies that are specific and applicable to pregnant women, the foetus, and, later, the newborn. Radiofrequency ultrasound spectrometry (REMS) has proven to be a useful tool in the assessment of bone mineral density (BMD) in pregnant women. Few studies have reported that transmission ultrasound can also be used to assess BMD in newborns. The advantages of this technology in the foetus and newborn are the absence of ionising radiation, ease of use, and, above all, the possibility of performing longitudinal studies from intrauterine to extrauterine life. The use of these technologies already in the intrauterine period could help prevent associated diseases, such as osteoporosis and osteopenia, which are characterised by a reduction in bone mass and degeneration of bone structure and lead to an increased risk of fractures in adulthood with considerable social repercussions for the related direct and indirect costs.

Introduction: Recent national guidelines recommending mitral valve replacement (MVR) for severe secondary mitral regurgitation have resulted in an increased utilization of mitral bioprosthesis. There is a paucity of data on how longitudinal clinical outcomes vary by prosthesis type. We examined long-term survival and risk of reoperation between patients having bovine vs. porcine MVR. Study Design . A retrospective analysis of MVR or MVR + coronary artery bypass graft (CABG) from 2001 to 2017 among seven hospitals reporting to a prospectively maintained clinical registry was conducted. The analytic cohort included 1,284 patients undergoing MVR (801 bovine and 483 porcine). Baseline comorbidities were balanced using 1 : 1 propensity score matching with 432 patients in each group. The primary end point was all-cause mortality. Secondary end points included in-hospital morbidity, 30-day mortality, length of stay, and risk of reoperation., Results: In the overall cohort, patients receiving porcine valves were more likely to have diabetes (19% bovine vs. 29% porcine; p < 0.001), COPD (20% bovine vs. 27% porcine; p =0.008), dialysis or creatinine >2 mg/dL (4% bovine vs. 7% porcine; p =0.03), and coronary artery disease (65% bovine vs. 77% porcine; p < 0.001). There was no difference in stroke, acute kidney injury, mediastinitis, pneumonia, length of stay, in-hospital morbidity, or 30-day mortality. In the overall cohort, there was a difference in long-term survival (porcine HR 1.17 (95% CI: 1.00-1.37; p =050)). However, there was no difference in reoperation (porcine HR 0.56 (95% CI: 0.23-1.32; p =0.185)). In the propensity-matched cohort, patients were matched on all baseline characteristics. There was no difference in postoperative complications or in-hospital morbidity and 30-day mortality. After 1 : 1 propensity score matching, there was no difference in long-term survival (porcine HR 0.97 (95% CI: 0.81-1.17; p =0.756)) or risk of reoperation (porcine HR 0.54 (95% CI: 0.20-1.47; p =0.225))., Conclusions: In this multicenter analysis of patients undergoing bioprosthetic MVR, there was no difference in perioperative complications and risk of reoperation of long-term survival after matching., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2023 M. Broadwin et al.)