Decreased blood vessel density and endothelial cell subset dynamics during ageing of the endocrine system.

Age-associated alterations of the hormone-secreting endocrine system cause organ dysfunction and disease states. However, the cell biology of endocrine tissue ageing remains poorly understood. Here, we perform comparative 3D imaging to understand age-related perturbations of the endothelial cell (EC) compartment in endocrine glands. Datasets of a wide range of markers highlight a decline in capillary and artery numbers, but not of perivascular cells in pancreas, testis and thyroid gland, with age in mice and humans. Further, angiogenesis and ß-cell expansion in the pancreas are coupled by a distinct age-dependent subset of ECs. While this EC subpopulation supports pancreatic ß cells, it declines during ageing concomitant with increased expression of the gap junction protein Gja1. EC-specific ablation of Gja1 restores ß-cell expansion in the aged pancreas. These results provide a proof of concept for understanding age-related vascular changes and imply that therapeutic targeting of blood vessels may restore aged endocrine tissue function. This comprehensive data atlas offers over > 1,000 multicolour volumes for exploration and research in endocrinology, ageing, matrix and vascular biology.

Endocrine Disorders and COVID-19.

The multifaceted interaction between coronavirus disease 2019 (COVID-19) and the endocrine system has been a major area of scientific research over the past two years. While common endocrine/metabolic disorders such as obesity and diabetes have been recognized among significant risk factors for COVID-19 severity, several endocrine organs were identified to be targeted by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). New-onset endocrine disorders related to COVID-19 were reported while long-term effects, if any, are yet to be determined. Meanwhile, the "stay home" measures during the pandemic caused interruption in the care of patients with pre-existing endocrine disorders and may have impeded the diagnosis and treatment of new ones. This review aims to outline this complex interaction between COVID-19 and endocrine disorders by synthesizing the current scientific knowledge obtained from clinical and pathophysiological studies, and to emphasize considerations for future research.

Clinical and genetic spectrum of RNF216-related disorder: a new case and literature review.

BACKGROUND: Cases of RNF216-related disorder have been reported sporadically. However, the clinical and genetic spectrum of this disorder has not been fully studied. METHODS: We identified an individual with a novel causative RNF216 variant in our institution and reviewed all individuals with causative RNF216 variants in previous reports. The clinical and genetic features of all the described individuals were analysed and summarised. RESULTS: Twenty-four individuals from 17 families with causative RNF216 variants were identified. The mean age at the onset of neurological symptoms was 29.2 years (range 18-49 years). Ataxia (57%) was the most frequent initial symptoms in individuals under 30 years old, while chorea (63%) was the most frequent initial symptom in individuals over 30 years old. Over 90% of individuals presented with cognitive impairment and hypogonadotropic hypogonadism throughout the disease. White matter lesions (96%) and cerebellar atrophy (92%) were the most common imaging findings. Twenty pathogenic variants in RNF216 were detected. The variants in 12 (71%) families were inherited in a monogenic recessive pattern, whereas the variants in 5 (29%) were inherited in a digenic pattern by acting with variants in other genes. The majority of the RNF216 variants (85%) resulted in amino acid changes or the truncation of the 'RING between RING' (RBR) domain or C-terminal extension. CONCLUSION: RNF216-related disorder is an inherited neuroendocrine disease characterised by cerebellar ataxia, chorea, cognitive impairment and hypogonadotropic hypogonadism. Most causative variants in patients with RNF216-related disorder influence the RBR domain or C-terminal extension of RNF216.

Autoimmune demyelination alters hypothalamic transcriptome and endocrine function.

The hypothalamus is a brain structure that is deputed to maintain organism homeostasis by regulating autonomic function and hormonal production as part of the neuroendocrine system. Dysfunction in hypothalamic activity results in behavioral alterations, depression, metabolic syndromes, fatigue, and infertility. Remarkably, many of these symptoms are associated with multiple sclerosis (MS), a chronic autoimmune disorder of the central nervous system (CNS) characterized by focal demyelination, immune cell infiltration into the brain parenchyma, and neurodegeneration. Furthermore, altered hormonal levels have been documented in MS patients, suggesting the putative involvement of hypothalamic deficits in MS clinical manifestations. Yet, a systematic analysis of hypothalamic function in response to neuroinflammatory stress is still lacking. To fill this gap, here we performed a longitudinal profiling of the hypothalamic transcriptome upon experimental autoimmune encephalomyelitis (EAE)-a murine disease model recapitulating key MS phenotypes at both histopathological and molecular levels. We show that changes in gene expression connected with an anti-inflammatory response start already at pre-onset and persist along EAE progression. Altered levels of hypothalamic neuropeptides were also detected, which possibly underlie homeostatic responses to stress and aberrant feeding behaviors. Last, a thorough investigation of the principal endocrine glands highlighted defects in the main steroidogenic pathways upon disease. Collectively, our findings corroborate the central role of hypothalamic dysfunction in CNS autoimmunity.

Expanding the Repertoire of ceDAF-12 Ligands for Modulation of the Steroid Endocrine System in C. Elegans.

Steroid hormones are essential for the biological processes of eukaryotic organisms. The steroid endocrine system of C. elegans, which includes dafachronic acids (DA) and the nuclear receptor ceDAF-12, provides a simple model for exploring the role of steroid hormone signaling pathways in animals. In this study, we show for the first time the feasibility of designing synthetic steroids that can modulate different physiological processes, such as development, reproduction and ageing, in relation to ceDAF-12. Our results not only confirm the conclusions derived from genetic studies linking these processes but also provide new chemical tools to selectively manipulate them, as we found that different compounds produce different phenotypic results. The structures of these compounds are much more diverse than those of endogenous hormones and analogues previously described by other researchers, allowing further development of the chemical modulation of the steroid endocrine system in C. elegans and related nematodes.

A new FGF15/19-mediated gut-to-heart axis controls cardiac hypertrophy.

FGF15 and its human orthologue, FGF19, are members of the endocrine FGF family and are secreted by ileal enterocytes in response to bile acids. FGF15/19 mainly targets the liver, but recent studies indicate that it also regulates skeletal muscle mass and adipose tissue plasticity. The aim of this study was to determine the role(s) of the enterokine FGF15/19 during the development of cardiac hypertrophy. Studies in a cohort of humans suffering from heart failure showed increased circulating levels of FGF19 compared with control individuals. We found that mice lacking FGF15 did not develop cardiac hypertrophy in response to three different pathophysiological stimuli (high-fat diet, isoproterenol, or cold exposure). The heart weight/tibia length ratio and the cardiomyocyte area (as measures of cardiac hypertrophy development) under hypertrophy-inducing conditions were lower in Fgf15-null mice than in wild-type mice, whereas the levels of the cardiac damage marker atrial natriuretic factor (Nppa) were up-regulated. Echocardiographic measurements showed similar results. Moreover, the genes involved in fatty acid metabolism were down-regulated in Fgf15-null mice. Conversely, experimental increases in FGF15 induced cardiac hypertrophy in vivo, without changes in Nppa and up-regulation of metabolic genes. Finally, in vitro studies using cardiomyocytes showed that FGF19 had a direct effect on these cells promoting hypertrophy. We have identified herein an inter-organ signaling pathway that runs from the gut to the heart, acts through the enterokine FGF15/19, and is involved in cardiac hypertrophy development and regulation of fatty acid metabolism in the myocardium. © 2023 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

Effects of chronic exposure to a high fat diet, nutritive or non-nutritive sweeteners on hypothalamic-pituitary-adrenal (HPA) and -gonadal (HPG) axes of male Sprague-Dawley rats.

PURPOSE: Diet-related factors are of great significance in the regulation of hypothalamic-pituitary-adrenal (HPA) and hypothalamic-pituitary-gonad (HPG) axes. In this study, we aimed to investigate the effects of chronic exposure to a high fat diet (HFD), fructose or sucralose on the endocrine functions. METHODS: Male, Sprague-Dawley rats received a normal chow diet, HFD, 10% fructose or 0.02% sucralose for 10 weeks. Behavioral changes were assessed by open field (OFT) and elevated plus-maze (EPM) tests at week 8. H&E staining was used to observe pathological changes in adrenal cortex, testis and perirenal adipose tissue. Serum hormone concentrations were quantified via enzyme-linked immunosorbent assay (ELISA). The mRNA expression levels of genes along the HPA and HPG axes were determined using real-time PCR. RESULTS: All types of dietary interventions increased body weight and disturbed metabolic homeostasis, with anxiogenic phenotype in behavioral tests and damage to cell morphology of adrenal cortex and testis being observed. Along the HPA axis, significantly increased corticotropin releasing hormone (CRH), adrenocorticotropic hormone (ACTH) and corticosterone (CORT) concentrations were observed in the HFD or 0.02% sucralose group. For HPG axis, gonadotropin-releasing hormone (GnRH) and estradiol (E2) concentrations were significantly increased in all dietary intervention groups, while decreased concentrations of follicle-stimulating hormone (FSH) and testosterone (T) were also detected. Moreover, transcriptional profiles of genes involved in the synthesis of hormones and corresponding hormone receptors were significantly altered. CONCLUSION: Long-term consumption of HFD, fructose or sucralose manifested deleterious effects on endocrine system and resulted in the dysregulation of HPA and HPG axes.

Gene expression and trace elements in Greenlandic ringed seals (Pusa hispida).

Marine top predators such as ringed seals biomagnify environmental contaminants; and with the increasing human activities in the Arctic, ringed seals are exposed to biologically significant concentrations of trace elements resulting in reproductive impairment, immunosuppression, and neurological damages. Little is known about the molecular effects of heavy metals on these vulnerable apex predators suffering from a rapidly changing Arctic with significant loss of sea-ice. In the present study, concentrations of cadmium (Cd), mercury (Hg) and selenium (Se) were measured in liver of sixteen Greenlandic ringed seals (nine adults and seven subadults) together with molecular biomarkers involved in bio-transformation, oxidative stress, endocrine disruption and immune activity in blood and blubber. The concentrations of trace elements increased in the following order: Hg > Se > Cd with levels of mercury and selenium being highest in adults. Aryl hydrocarbon receptor nuclear translocator (ARNT), peroxisome proliferator activated receptor alpha (PPARα, estrogen receptor alpha (ESR1), thyroid hormone receptor alpha (TRα) and interleukin - 2 (IL-2) mRNA transcript levels were highest in blubber, while heat shock protein 70 (HSP70) and interleukin - 10 (IL-10) were significantly higher in blood. There were no significant correlations between the concentrations of trace elements and mRNA transcript levels suggesting that stressors other than the trace elements investigated are responsible for the changes in gene expression levels. Since Hg seems to increase in Greenlandic ringed seals, there is a need to re-enforce health monitoring of this ringed seal population.

Synergistic effects of hormones on structural and functional maturation of cardiomyocytes and implications for heart regeneration.

The limited endogenous regenerative capacity of the human heart renders cardiovascular diseases a major health threat, thus motivating intense research on in vitro heart cell generation and cell replacement therapies. However, so far, in vitro-generated cardiomyocytes share a rather fetal phenotype, limiting their utility for drug testing and cell-based heart repair. Various strategies to foster cellular maturation provide some success, but fully matured cardiomyocytes are still to be achieved. Today, several hormones are recognized for their effects on cardiomyocyte proliferation, differentiation, and function. Here, we will discuss how the endocrine system impacts cardiomyocyte maturation. After detailing which features characterize a mature phenotype, we will contemplate hormones most promising to induce such a phenotype, the routes of their action, and experimental evidence for their significance in this process. Due to their pleiotropic effects, hormones might be not only valuable to improve in vitro heart cell generation but also beneficial for in vivo heart regeneration. Accordingly, we will also contemplate how the presented hormones might be exploited for hormone-based regenerative therapies.

Pathogenic variations in MAML2 and MAMLD1 contribute to congenital hypothyroidism due to dyshormonogenesis by regulating the Notch signalling pathway.

BACKGROUND: In several countries, thyroid dyshormonogenesis is more common than thyroid dysgenesis in patients with congenital hypothyroidism (CH). However, known pathogenic genes are limited to those directly involved in hormone biosynthesis. The aetiology and pathogenesis of thyroid dyshormonogenesis remain unknown in many patients. METHODS: To identify additional candidate pathogenetic genes, we performed next-generation sequencing in 538 patients with CH and then confirmed the functions of the identified genes in vitro using HEK293T and Nthy-ori 3.1 cells, and in vivo using zebrafish and mouse model organisms. RESULTS: We identified one pathogenic MAML2 variant and two pathogenic MAMLD1 variants that downregulated canonical Notch signalling in three patients with CH. Zebrafish and mice treated with N-[N-(3,5-difluorophenacetyl)-l-alanyl]-S-phenylglycine t-butylester, a γ-secretase inhibitor exhibited clinical manifestations of hypothyroidism and thyroid dyshormonogenesis. Through organoid culture of primary mouse thyroid cells and transcriptome sequencing, we demonstrated that Notch signalling within thyroid cells directly affects thyroid hormone biosynthesis rather than follicular formation. Additionally, these three variants blocked the expression of genes associated with thyroid hormone biosynthesis, which was restored by HES1 expression. The MAML2 variant exerted a dominant-negative effect on both the canonical pathway and thyroid hormone biosynthesis. MAMLD1 also regulated hormone biosynthesis through the expression of HES3, the target gene of the non-canonical pathway. CONCLUSIONS: This study identified three mastermind-like family gene variants in CH and revealed that both canonical and non-canonical Notch signalling affected thyroid hormone biosynthesis.

Effects of exercise, metformin and their combination on glucose metabolism in individuals with abnormal glycaemic control: a systematic review and network meta-analysis.

OBJECTIVE: To compare the efficacy of exercise, metformin and their combination on glucose metabolism in individuals with abnormal glycaemic control. DESIGN: Systematic review and network meta-analysis. DATA SOURCES: Embase, Web of Science, PubMed/MEDLINE and SPORTDiscus. ELIGIBILITY CRITERIA: Randomised controlled trials involving exercise, metformin or their combined treatments in individuals with prediabetes or type 2 diabetes mellitus (T2DM) were included. Outcomes included haemoglobin A1c (HbA1c), 2-hour glucose during oral glucose tolerance test, fasting glucose, fasting insulin and homeostasis model assessment of insulin resistance (HOMA-IR). RESULTS: 407 articles with 410 randomised controlled trials (n=33 802) were included. In prediabetes, the exercise showed greater efficacy than metformin on HbA1c levels (mean difference -0.16%, 95% CI (-0.23 to -0.09) vs -0.10%, 95% CI (-0.21 to 0.02)), 2-hour glucose (-0.68 mmol/L, 95% CI (-0.97 to -0.39) vs 0.01 mmol/L, 95% CI (-0.38 to 0.41)) and HOMA-IR (-0.54, 95% CI (-0.71 to -0.36) vs -0.23, 95% CI (-0.55 to 0.10)), while the efficacy on fasting glucose was comparable (-0.26 mmol/L, 95% CI (-0.32 to -0.19) vs -0.33 mmol/L, 95% CI (-0.45 to -0.21)). In T2DM, metformin was more efficacious than exercise on HbA1c (-0.88%, 95% CI (-1.07 to -0.69) vs -0.48%, 95% CI (-0.58 to -0.38)), 2-hour glucose (-2.55 mmol/L, 95% CI (-3.24 to -1.86) vs -0.97 mmol/L, 95% CI (-1.52 to -0.42)) and fasting glucose (-1.52 mmol/L, 95% CI (-1.73 to -1.31) vs -0.85 mmol/L, 95% CI (-0.96 to -0.74)); exercise+metformin also showed greater efficacy in improving HbA1c (-1.23%, 95% CI (-2.41 to -0.05)) and fasting glucose (-2.02 mmol/L, 95% CI (-3.31 to -0.74)) than each treatment alone. However, the efficacies were modified by exercise modality and metformin dosage. CONCLUSION: Exercise, metformin and their combination are efficacious in improving glucose metabolism in both prediabetes and T2DM. The efficacy of exercise appears to be superior to metformin in prediabetes, but metformin appears to be superior to exercise in patients with T2DM. PROSPERO REGISTRATION NUMBER: CRD42023400622.

Hypothalamic-pituitary-ovarian axis suppression is common among women during US Army Basic Combat Training.

OBJECTIVE: Less than half of servicewomen report loss of menses during initial military training. However, self-reported menstrual status may not accurately reflect hypothalamic-pituitary-ovarian (HPO) axis suppression and may underestimate reproductive health consequences of military training. Our aim was to characterise HPO axis function during US Army Basic Combat Training (BCT) in non-hormonal contraceptive-using women and explore potential contributors to HPO axis suppression. METHODS: In this 10-week prospective observational study, we enrolled multi-ethnic women entering BCT. Trainees provided daily first-morning voided urine, and weekly blood samples during BCT. Urinary luteinising hormone, follicle stimulating hormone, and metabolites of estradiol and progesterone were measured by chemiluminescent assays (Siemens Centaur XP) to determine hormone patterns and luteal activity. We measured body composition, via dual-energy X-ray absorptiometry, at the beginning and end of BCT. RESULTS: Trainees (n=55) were young (mean (95% CI): 22 (22, 23) years) with average body mass index (23.9 (23.1, 24.7) kg/m2). Most trainees (78%) reported regular menstrual cycles before BCT. During BCT, 23 (42%) trainees reported regular menses. However, only seven trainees (12.5%) had menstrual cycles with evidence of luteal activity (ELA) (ie, presumed ovulation), all with shortened luteal phases. 41 trainees (75%) showed no ELA (NELA), and 7 (12.5%) were categorised as indeterminant. Overall, women gained body mass and lean mass, but lost fat mass during BCT. Changes in body mass and composition appear unrelated to luteal activity. CONCLUSIONS: Our findings reveal profound HPO axis suppression with NELA in the majority of women during BCT. This HPO axis suppression occurs among women who report normal menstrual cycles.

Can the analysis of chromatin texture and nuclear fractal dimensions serve as effective means to distinguish non-invasive follicular thyroid neoplasm with papillary-like nuclear features from other malignancies with follicular pattern in the thyroid?: a study.

OBJECTIVE: Thyroid carcinoma ranks as the 9th most prevalent global cancer, accounting for 586,202 cases and 43,636 deaths in 2020. Computerized image analysis, utilizing artificial intelligence algorithms, emerges as a potential tool for tumor evaluation. AIM: This study aims to assess and compare chromatin textural characteristics and nuclear dimensions in follicular neoplasms through gray-level co-occurrence matrix (GLCM), fractal, and morphometric analysis. METHOD: A retrospective cross-sectional study involving 115 thyroid malignancies, specifically 49 papillary thyroid carcinomas with follicular morphology, was conducted from July 2021 to July 2023. Ethical approval was obtained, and histopathological examination, along with image analysis, was performed using ImageJ software. RESULTS: A statistically significant difference was observed in contrast (2.426 (1.774-3.412) vs 2.664 (1.963-3.610), p = .002), correlation (1.202 (1.071-1.298) vs 0.892 (0.833-0.946), p = .01), and ASM (0.071 (0.090-0.131) vs 0.044 (0.019-0.102), p = .036) between NIFTP and IFVPTC. However, morphometric parameters did not yield statistically significant differences among histological variants. CONCLUSION: Computerized image analysis, though promising in subtype discrimination, requires further refinement and integration with traditional diagnostic parameters. The study suggests potential applications in scenarios where conventional histopathological assessment faces limitations due to limited tissue availability. Despite limitations such as a small sample size and a retrospective design, the findings contribute to understanding thyroid carcinoma characteristics and underscore the need for comprehensive evaluations integrating various diagnostic modalities.

Assessing the Risks of Pesticide Exposure: Implications for Endocrine Disruption and Male Fertility.

Pesticides serve as essential tools in agriculture and public health, aiding in pest control and disease management. However, their widespread use has prompted concerns regarding their adverse effects on humans and animals. This review offers a comprehensive examination of the toxicity profile of pesticides, focusing on their detrimental impacts on the nervous, hepatic, cardiac, and pulmonary systems, and their impact on reproductive functions. Additionally, it discusses how pesticides mimic hormones, thereby inducing dysfunction in the endocrine system. Pesticides disrupt the endocrine system, leading to neurological impairments, hepatocellular abnormalities, cardiac dysfunction, and respiratory issues. Furthermore, they also exert adverse effects on reproductive organs, disrupting hormone levels and causing reproductive dysfunction. Mechanistically, pesticides interfere with neurotransmitter function, enzyme activity, and hormone regulation. This review highlights the effects of pesticides on male reproduction, particularly sperm capacitation, the process wherein ejaculated sperm undergo physiological changes within the female reproductive tract, acquiring the ability to fertilize an oocyte. Pesticides have been reported to inhibit the morphological changes crucial for sperm capacitation, resulting in poor sperm capacitation and eventual male infertility. Understanding the toxic effects of pesticides is crucial for mitigating their impact on human and animal health, and in guiding future research endeavors.

Mechanisms of Abnormal Lipid Metabolism in the Pathogenesis of Disease.

Lipid metabolism is a critical component in preserving homeostasis and health, and lipids are significant chemicals involved in energy metabolism in living things. With the growing interest in lipid metabolism in recent years, an increasing number of studies have demonstrated the close relationship between abnormalities in lipid metabolism and the development of numerous human diseases, including cancer, cardiovascular, neurological, and endocrine system diseases. Thus, understanding how aberrant lipid metabolism contributes to the development of related diseases and how it works offers a theoretical foundation for treating and preventing related human diseases as well as new avenues for the targeted treatment of related diseases. Therefore, we discuss the processes of aberrant lipid metabolism in various human diseases in this review, including diseases of the cardiovascular system, neurodegenerative diseases, endocrine system diseases (such as obesity and type 2 diabetes mellitus), and other diseases including cancer.

Considering the impact of shift working on health.

Shift work is necessary for the provision of health services, especially in hospitals as it is the only way to provide continuous care to patients. Working at night is inconsistent with the body's biological clock and night shift working hugely disrupts the circadian and sleep wake cycles. In 2020, the World Health Organization classified night shift working as being a 'probable' class 2A carcinogen and a number of independent cohort studies of both night workers and shift workers have observed increased incidence of certain cancers. Altered sleep timing, food timing and light exposure typical for shift workers leads to an acute circadian disruption and misalignment of regulatory hormones. This straying from synchronisation has been shown to result in individuals being more vulnerable to a number of chronic health conditions. Night shift work disrupts the normal sleep-wake cycle, often leading to shortened sleep duration and excessive fatigue and the results of this are far reaching. This article will explore the full impact of shift working, questioning if current practices employed within the NHS should continue.

The underlying sex differences in neuroendocrine adaptations relevant to Myalgic Encephalomyelitis Chronic Fatigue Syndrome.

INTRODUCTION: Myalgic Encephalomyelitis/ Chronic Fatigue Syndrome (ME/CFS) is a complex multisystem disease characterised by severe and disabling new-onset symptoms of post-exertional malaise (PEM), fatigue, brain fog, and sleep dysfunction that lasts for at least six months. Accumulating evidence suggests that sex and endocrine events have a significant influence on symptom onset and moderation of ME/CFS, with female sex being one of the most consistent and credible predictive risk factors associated with diagnosis. Such sex differences suggest sex chromosomes and sex steroids may play a part in the development of the condition or moderation of symptoms, although this has yet to be explored in detail. METHODS/AIMS: This narrative review outlines sex differences in ME/CFS in terms of vulnerability factors and clinical phenotype and explores the known sex differences in neuroendocrine systems affected in ME/CFS and how this may relate to disease risk, onset, pathophysiology, and potential treatment avenues. CONCLUSIONS: There is clear evidence of a sex dimorphism with regards to prevalence (3:1 female preponderance), clinical phenotypes, and aetiological triggers prior to symptom onset of ME/CFS. Endocrinological events, particularly those throughout the female lifespan, are associated with ME/CFS and include reproductive menstrual cycle fluctuations, pregnancy, post-partum and perimenopause. Further, there is evidence for gonadal sex, adrenal stress and renal neuroendocrine systems as implicated in ME/CFS, including changes in estrogen, progesterone compounds, aldosterone, and cortisol levels, of which there are established sex differences. The broad effects of steroid hormones on the physiological systems may also speak to the diversity of ME/CFS symptomatology observed in patients. Further attention must be paid to sex, age, and steroid biology in ME/CFS.

Endocrine complications after hematopoietic stem cell transplantation during childhood-Results from a close follow-up in a cohort of 152 patients.

CONTEXT: Haematopoietic stem cell transplantation (HSCT) is a therapeutic option for numerous haematologic diseases and solid tumours. Increasing indications for HSCT and reduction in associated mortality have been raising the number of paediatric HSCT survivors and their long-term toxicities. OBJECTIVE: To characterize the endocrine disorders developed after HSCT. DESIGN AND PATIENTS: Retrospective analysis of 152 patients submitted to HSCT in paediatric age with at least 24 months of follow-up at our endocrine late-effects clinics. RESULTS: Patients were followed up for 9.9 (interquartile range [IQR]: 12.2) years. The median age at HSCT was 7.5 (IQR: 9) years. At least one endocrine complication was observed in 65.1% of the patients. Primary hypogonadism was detected in 34.2%. Female gender (p < .001), HSCT > 10 years old (p = .01) and chemotherapy before HSCT (p < .001) were identified as risk factors for developing gonadal dysfunction. Growth hormone deficiency (GHD) occurred in 23.0% with a mean stature Z-score at diagnosis of -1.8 ± 1.4. GHD was associated with cranial (p < .001) and HSCT < 10 years old (p ≤ 0.001). Patients who were exposed to total body irradiation (TBI) were at higher risk for primary hypothyroidism (22.3%) (p = .01), thyroid nodules (17.1%) (p < .001), thyroid carcinoma (5.3%) (p < .001), dyslipidaemia (19.1%) (p < .001) and disturbance of carbohydrate metabolism (19.1%) (p < .001). CONCLUSION: At least one endocrine complication was diagnosed in 65.1% of patients, with gonadal dysfunction being the most prevalent. The conditioning regimen with TBI was a risk factor for the development of several endocrine disorders. This study is one of the largest series evaluating the endocrine disorders among survivors of paediatric HSCT and intends to reinforce the importance of routine follow-up of these patients.

Emissions and mitigation potential of endocrine disruptors during outdoor exercise: Fate, transport, and implications for human health.

The endocrine system is responsible for secreting and controlling hormones crucial in regulating key body activities. However, endocrine disruptors or endocrine-disrupting chemicals (EDCs) can harm human health and well-being by interfering with this complex process. This report seeks to assess the present state of understanding about endocrine disruptors in China, including their origins, impacts, and obstacles, and to provide actionable recommendations for reducing exposure and mitigating negative effects. Strong negative correlations between ANOE and rural ecological compensation (REC) and a negative correlation between ANOE and forest coverage (FC) were found in this analysis of the relationships between agricultural nitrous oxide emissions (ANOE), agricultural methane emissions (AME), and land use and land cover variables (LUPC). Just as LUPC is significantly inversely related to FC, AME is positively related. The team uses a gradient-boosted model (GBM) with a Gaussian loss function and fine-tunes the model's parameters to achieve optimal performance and reliable prediction results. With a relative relevance score of 90.36 for ANOE and 67.64 for AME, the analysis shows that LUPC is the most important factor in influencing emission levels. This study aims to increase knowledge of endocrine disruptors' potential advantages and disadvantages in outdoor exercise. The study aims to aid in preventing and managing many diseases and disorders caused by hormonal imbalances or disruptions by examining the origins, effects, and potential mitigation of these substances during outdoor activity. Safe and healthful outdoor exercise is promoted by the study's efforts to discover and implement effective and sustainable solutions to decrease emissions and exposure to endocrine disruptors. This comprehensive study aims to promote a healthier and more sustainable environment for individuals engaging in outdoor exercise by synthesizing current knowledge, providing practical recommendations, and emphasizing the importance of awareness and action.

Circadian Rhythm and Endocrinological Control on the Swimming and Sand Burrowing Behaviors of Japanese Sand Lances Ammodytes spp. (Uranoscopiformes, Ammodytidae).

In diurnal and nocturnal organisms, daily activity is regulated by the perception of environmental stimuli and circadian rhythms, which enable organisms to maintain their essential behaviors. The Japanese sand lances genus Ammodytes are coastal marine fish that exhibit unique nocturnal sand burrowing behavior. To elucidate the extrinsic and intrinsic regulation of this behavior and its endocrinological basis, we conducted a series of rearing experiments under various light conditions and hormone administrations. Under a light-dark photoperiod, the fish showed three types of behavior: sand buried, head-exposed from sand, and swimming/feeding. During the transition from dark to light periods, the fish first showed head exposure, followed by swimming and foraging, and buried themselves in the sand immediately after shifting to the dark period. Under constant light conditions, fish exhibited swimming behavior during the period corresponding to the acclimated light period. In addition, swimming did not occur under constant dark conditions but head exposure was observed at the time of the dark-light transition during acclimation. These observations indicate that the essential behavior of sand lances is regulated by both light and circadian rhythms. Subsequently, a melatonin-containing diet promoted the onset of burrowing in 10 to 120 min in a dose-dependent manner at 0.3-128 µg/g-diet, suggesting the direct behavioral regulation by this hormone. These findings suggest that the behavior of sand lances is strictly regulated by an intrinsic mechanism and that melatonin is a regulatory endocrine factor that induces burrowing behavior.