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Journal of Hazardous Materials Aug 2023Homologous recombination (HR) during early oogenesis repairs programmed double-strand breaks (DSBs) to ensure female fertility and offspring health. The exposure of...
Homologous recombination (HR) during early oogenesis repairs programmed double-strand breaks (DSBs) to ensure female fertility and offspring health. The exposure of fetal ovaries to endocrine disrupting chemicals (EDCs) can cause reproductive disorders in the adulthood. The EDC dibutyl phthalate (DBP) is widely distributed in flexible plastic products, leading to ubiquitous human exposure. Here, we report that maternal exposure to DBP caused gross aberrations in meiotic prophase I of fetal oocytes, including delayed progression, impaired DNA damage response, uncoupled localization of DMC1 and RAD51, and decreased HR. However, programmed DSBs were efficiently repaired. DBP exposure negatively regulated lysine crotonylation (Kcr) of MSH6. Similar meiotic defects were observed in fetal ovaries with targeted disruption of Msh6, and mutation of K544cr of MSH6 impaired its association with Ku70, thereby promoting non-homologous end joining (NHEJ) and inhibiting HR. Unlike mature F1 females, F2 female mice exhibited premature follicular activation, precocious puberty, and anxiety-like behaviors. Therefore, DBP can influence early meiotic events, and Kcr of MSH6 may regulate preferential induction of HR or NHEJ for DNA repair during meiosis.
Topics: Humans; Female; Mice; Animals; Adult; Dibutyl Phthalate; Meiosis; Maternal Exposure; DNA-Binding Proteins; Homologous Recombination; DNA Repair; Oocytes
PubMed: 37167869
DOI: 10.1016/j.jhazmat.2023.131540 -
Scientific Reports Sep 2023This study was an attempt to examine the changes in serum levels of ghrelin and leptin after 12-weeks of aerobic training and gonadotropin releasing hormone agonist...
This study was an attempt to examine the changes in serum levels of ghrelin and leptin after 12-weeks of aerobic training and gonadotropin releasing hormone agonist (GnRH) treatment in girls with central precocious puberty. Thirty girls (6-8 years old) with precocious puberty who had received Triptorelin were randomly divided in two groups (medication and medication + training). Fifteen age-matched healthy girls (without precocious puberty) were also included as the control group. The medication + training group submitted an aerobic training program for 3 days/week with 20-75 min per day and 45-75% of maximum heart rate for 12-weeks. Serum levels of leptin, ghrelin, cholesterol, triglycerides and body mass index (BMI) were determined at baseline and 48 h after the last training session. The results indicated that leptin significantly decreased (p = 0.001) and ghrelin significantly increased (p = 0.001) in the medication + training group but no significant difference was observed in the ghrelin (p = 1) and leptin (p = 0.78) in the medication group. Leptin to ghrelin ratio indicated a decrease in medicine + training group (p = 0.028). Ghrelin were negatively correlated with leptin and BMI. The data indicated that aerobic training increased ghrelin and reduced leptin and leptin to ghrelin ratio but GnRH agonist treatment had no effect on plasma leptin and ghrelin levels.
Topics: Female; Humans; Child; Ghrelin; Puberty, Precocious; Leptin; Body Mass Index; Triptorelin Pamoate
PubMed: 37735188
DOI: 10.1038/s41598-023-42828-1 -
Annals of Pediatric Endocrinology &... Sep 2023
Central precocious puberty: is routine brain MRI screening necessary for girls?: Commentary on "Brain magnetic resonance imaging (MRI) findings in central precocious puberty patients: is routine MRI necessary for newly diagnosed patients?".
PubMed: 37798890
DOI: 10.6065/apem.2322096edi07 -
Reproductive Biology and Endocrinology... Oct 2023Cranial radiotherapy (CRT) is recommended to high-risk pediatric patients with acute lymphoblastic leukemia or aggressive non-Hodgkin's lymphoma (ALL/NHL). However,... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Cranial radiotherapy (CRT) is recommended to high-risk pediatric patients with acute lymphoblastic leukemia or aggressive non-Hodgkin's lymphoma (ALL/NHL). However, effects of CRT treatment on the development of metabolic/endocrine disorders remain unclear. This meta-analysis aimed to identify metabolic and endocrine disturbances in survivors of childhood-onset and CRT-treated ALL/NHL.
METHODS
Different online databases were searched using restricted search fields. Follow-up data and outcome measurements, including the prevalence of growth hormone (GH) deficiency, hypothyroidism, vitamin D deficiency, overweight/obesity, and hypogonadism were recorded. The height data was indicated by height-standard deviation score (height-SDS). Statistical estimates such as odds ratio (OR) and weighted standard mean difference (SMD) were compared between additional CRT treatment group and non-CRT treatment group. Study-to-study heterogeneity was calculated by calculating I-squared statistic, and fixed/random effect was applied to synthesize and analyze extracted data.
RESULTS
Fifteen studies were included (4269 patients in total). Adult height SDS was lower in CRT-treated patients (pooled SMD = -0.581, 95% CI: -0.649--0.512), and CRT-treated patients were likely to develop short stature (pooled OR = 2.289, 95% CI:1.674-3.130). Regardless of the study year, which potentially reflects the state-of-the-art CRT technique, the prevalence of short stature and GH deficiency was time-independent. Additionally, previous CRT can increase the risk of precocious puberty (pooled OR = 2.937, 95% CI: 1.281-6.736), hypothyroidism (pooled OR = 2.057, 95% CI:1.510-2.801), and hypogonadism (pooled OR = 3.098, 95% CI:2.521-3.807). However, the risk of being overweight/obese was similar between the patients with and without CRT (pooled OR = 1.278, 95% CI: 0.675-2.421).
CONCLUSION
Childhood-onset and CRT-treated ALL/NHL survivors are likely to have shorter height, precocious puberty, hypothyroidism, and hypogonadism.
Topics: Adult; Humans; Child; Puberty, Precocious; Overweight; Endocrine System Diseases; Survivors; Metabolic Diseases; Obesity; Hypothyroidism; Hypogonadism
PubMed: 37794442
DOI: 10.1186/s12958-023-01137-y -
Pediatric Research Apr 2024Obesity is an important cause for the precocious or early puberty. However, the association between obesity-related loci and the risk of precocious puberty as well as...
BACKGROUND
Obesity is an important cause for the precocious or early puberty. However, the association between obesity-related loci and the risk of precocious puberty as well as the effect of gene-environment interaction are unclear, especially in the Chinese children population.
METHODS
This was a case-control study using baseline data from two cohorts and hospital cases in China. 15 SNPs loci and several environmental factors were included in the analysis of 1201 participants. Chi-square test and logistic regression were used to analyze the association between SNPs and precocious puberty. Additionally, exploratory factor analysis was conducted on 13 environmental variables, and then to explore their interaction with genes on precocious puberty.
RESULTS
The effect allele C of rs571312, and G of rs12970134 MC4R were associated with precocious puberty in girls with obesity. Regarding the gene-environment interaction, we found that when girls were in the high socioeconomic status, the rs571312 (OR: 3.996; 95% CI: 1.694-9.423) and rs12970134 (OR: 3.529; 95% CI: 1.452-8.573) risk genotypes had a greater effect on precocious puberty.
CONCLUSIONS
The obesity risk gene polymorphisms MC4R rs571312 and rs12970134 were associated with precocious puberty in Chinese girls with obesity, and girls with risk genotypes and high socioeconomic status should be given extra attention.
IMPACT
This is the first study that identified the association between rs571312 and rs12970134 of MC4R gene and precocious puberty in Chinese children. We found that when girls were in the high socioeconomic status, the risk genotypes of rs571312 and rs12970134 had a greater effect on precocious puberty. The results of this study have great public health implications. It is recommended that girls who are in high socioeconomic status and have a high genetic risk for early sexual maturity should closely monitor their pubertal development and consider early intervention strategies.
PubMed: 38649724
DOI: 10.1038/s41390-024-03168-6 -
Journal of Pediatric Endocrinology &... Mar 2024Artificial intelligence (AI) in medicine is transforming healthcare by automating system tasks, assisting in diagnostics, predicting patient outcomes and personalising... (Review)
Review
Artificial intelligence (AI) in medicine is transforming healthcare by automating system tasks, assisting in diagnostics, predicting patient outcomes and personalising patient care, founded on the ability to analyse vast datasets. In paediatric endocrinology, AI has been developed for diabetes, for insulin dose adjustment, detection of hypoglycaemia and retinopathy screening; bone age assessment and thyroid nodule screening; the identification of growth disorders; the diagnosis of precocious puberty; and the use of facial recognition algorithms in conditions such as Cushing syndrome, acromegaly, congenital adrenal hyperplasia and Turner syndrome. AI can also predict those most at risk from childhood obesity by stratifying future interventions to modify lifestyle. AI will facilitate personalised healthcare by integrating data from 'omics' analysis, lifestyle tracking, medical history, laboratory and imaging, therapy response and treatment adherence from multiple sources. As data acquisition and processing becomes fundamental, data privacy and protecting children's health data is crucial. Minimising algorithmic bias generated by AI analysis for rare conditions seen in paediatric endocrinology is an important determinant of AI validity in clinical practice. AI cannot create the patient-doctor relationship or assess the wider holistic determinants of care. Children have individual needs and vulnerabilities and are considered in the context of family relationships and dynamics. Importantly, whilst AI provides value through augmenting efficiency and accuracy, it must not be used to replace clinical skills.
Topics: Child; Humans; Artificial Intelligence; Pediatric Obesity; Algorithms; Endocrinology; Insulin
PubMed: 38183676
DOI: 10.1515/jpem-2023-0554 -
Diabetes Research and Clinical Practice Sep 2023To study the age of pubertal onset and secular trend in boys with Type 1 diabetes mellitus (T1DM) followed in two centers in North Greece.
AIMS
To study the age of pubertal onset and secular trend in boys with Type 1 diabetes mellitus (T1DM) followed in two centers in North Greece.
METHODS
Boys with T1DM visited the Outpatient Clinics of the 1st and 2nd Department of Paediatrics of Aristotle University of Thessaloniki from March until June 2022 were enrolled. Recent anthropometric data were recorded during the follow-up visit whereas previous anthropometric data and demographic data were collected from medical files. A volume of testis > 3 ml was indicative for the onset of puberty.
RESULTS
A total of 46 boys with T1DM with documented pubertal onset after the diagnosis of T1DM were included in the study. Precocious puberty (<9 years old) was recorded in 5 boys (10.2 %), early puberty (<10 years but >9 years) in 10 (20.4 %) and 34 (69.4 %) entered puberty normally. The duration of T1DM was inversely correlated to the likelihood of earlier puberty (P < 0.001). However, no notable year predominance was observed suggesting no COVID-19 effect.
CONCLUSION
A considerable number of Greek boys with T1DM appear to develop precocious and early puberty, raising thoughts regarding diabetes management and other possible cofactors.
Topics: Male; Humans; Child; Diabetes Mellitus, Type 1; Puberty; Testis; Puberty, Precocious; Anthropometry
PubMed: 37478976
DOI: 10.1016/j.diabres.2023.110837 -
Nursing Children and Young People Aug 2023Puberty is an important marker of health and development in a child's life. Complex neuroendocrine factors contribute to the onset of puberty. While pubertal changes...
Puberty is an important marker of health and development in a child's life. Complex neuroendocrine factors contribute to the onset of puberty. While pubertal changes usually occur between the ages of 12 and 13 years, some children may attain puberty before the age of eight years for girls and nine years for boys, which is termed precocious puberty. A literature review was conducted to explore the incidence and prevalence of precocious puberty, identify contributory factors, and recognise management and preventive measures. In addition, the effects on the child and family and the role of nurses were considered. The incidence and prevalence of precocious puberty are increasing. Obesity, early childhood stressors, environmental toxins, increased access to the internet and socioeconomic status are contributory factors. Pharmacological and psychological interventions may be used to manage precocious puberty. Lifestyle modifications such as healthy eating are important preventive measures. Nurses have an important role in preparing children and families, and supporting their psychological and social well-being.
PubMed: 37547941
DOI: 10.7748/ncyp.2023.e1480 -
The Journal of Clinical Endocrinology... Jan 2024Nonprogressive premature thelarche (PT) is a self-limiting variant of early puberty, while idiopathic central precocious puberty (ICPP) is a disorder that causes...
CONTEXT
Nonprogressive premature thelarche (PT) is a self-limiting variant of early puberty, while idiopathic central precocious puberty (ICPP) is a disorder that causes progressive development of secondary sexual characteristics and often requires treatment. The diagnostic differentiation between these conditions is important but can be challenging since they often both initially present clinically with isolated breast development.
OBJECTIVE
To describe relevant clinical variables in a large cohort of girls referred for early puberty, and to evaluate clinical and biochemical parameters to distinguish between girls with ICPP and PT.
METHODS
This retrospective study included 1361 girls referred with signs of early puberty to a single, tertiary center from 2009 to 2019. We evaluated clinical presentation, medical history, growth velocity, bone age, hormonal serum concentrations, and gonadotropin-releasing hormone (GnRH) test results.
RESULTS
Central precocious puberty was diagnosed in 11% (ICPP: n = 143, organic CPP: n = 11) girls, whereas 8% (n = 91 girls) presented with PT. Receiver operating characteristic (ROC) analysis showed several biochemical and anthropometric markers as potential parameters to differentiate between ICPP and PT; however, none were individually adequate. Principal component analysis (PCA)-derived clinical and hormone profiles could predict girls with ICPP from girls with PT with a specificity of 90% and sensitivity of 84%, outperforming any single marker.
CONCLUSION
Differentiation of girls with ICPP and PT can be supported by individual clinical and biochemical parameters. However, dimension reduction of clinical and hormonal profiles by PCA improved the diagnostic value, which in the future may support the diagnostic process as a supplement to the GnRH test in evaluation of pubertal disorders.
Topics: Female; Humans; Puberty, Precocious; Retrospective Studies; Principal Component Analysis; ROC Curve; Gonadotropin-Releasing Hormone
PubMed: 37698163
DOI: 10.1210/clinem/dgad535 -
Epilepsy Research Sep 2023To determine long-term outcome for seizure control and clinical predictors for seizure freedom in patients undergoing surgical treatment for epilepsy associated with...
PURPOSE
To determine long-term outcome for seizure control and clinical predictors for seizure freedom in patients undergoing surgical treatment for epilepsy associated with hypothalamic hamartoma (HH).
METHODS
155 patients underwent surgical treatment for HHs and treatment-resistant epilepsy at one center (Barrow Neurological Institute at St. Joseph's Hospital and Medical Center, Phoenix, Arizona, USA) between February 2003 and June 2010. Data collection included medical record review and direct follow-up interviews to determine seizure outcome. Statistical analysis included descriptive summaries of patient characteristics and time-to-event analysis for seizure freedom.
RESULTS
Long-term survival with follow-up of at least five years since first surgical treatment was available for 108 patients (69.7% of the treatment cohort). The surgical approach for first HH intervention consisted of transventricular endoscopic resection (n = 57; 52.8%), transcallosal interforniceal resection (n = 35; 32.4%), pterional resection (n = 7; 6.5%), and gamma knife radiosurgery (n = 9; 8.3%). Multiple surgical procedures were required for 39 patients (36.1%). There were 10 known deaths from all causes in the treatment cohort (6.5%). Of these, one (0.6%) was related to immediate complications of HH surgery, three (1.9%) were attributed to Sudden Unexpected Death in Epileptic Persons (SUDEP), and one (0.6%) to complications of status epilepticus. For surviving patients with long-term follow-up, 55 (50.9%) were seizure-free for all seizure types. Univariable analysis showed that seizure-freedom was related to 1) absence of a pre-operative history for central precocious puberty (p = 0.01), and 2) higher percentage of HH lesion disconnection after surgery (p = 0.047). Kaplan-Meier survival analysis shows that long-term seizure outcome following HH surgery is comparable to short-term results.
SUMMARY
These uncontrolled observational results show that long-term seizure control following HH surgical treatment is comparable to other forms of epilepsy surgery. Late relapse (at least one year after surgery) and SUDEP do occur, but in a relatively small number of treated patients. These results inform clinical practice and serve as a comparable benchmark for newer technologies for HH surgery, such as magnetic resonance imaging-guided laser interstitial thermal therapy, where long-term outcome results are not yet available.
Topics: Humans; Sudden Unexpected Death in Epilepsy; Treatment Outcome; Hypothalamic Diseases; Epilepsy; Hamartoma; Magnetic Resonance Imaging
PubMed: 37454523
DOI: 10.1016/j.eplepsyres.2023.107186