Context:Bisphenol A (BPA) and its analogues disrupt endocrine functions, adversely impacting oocyte meiosis, maturation, and granulosa cell (GC) steroidogenesis. Objective:To identify clinical factors, particularly adiposity and age, influencing ovarian cell sensitivity to bisphenol (BP) exposure. Methods:This study analyzed a cohort of 368 women undergoing assisted reproductive technology (ART) from 2019 to 2023. Four BPs (BPA, BPS, BPF, and BPAF) were quantified, and ART outcomes (eg, oocyte count, embryo quality, and pregnancy rates) were assessed using regression models. GCs from 156 patients were cultured and exposed to BPS for 48 hours to evaluate progesterone and estradiol secretion based on clinical parameters. Results:BPS and BPA were the most prevalent BPs in follicular fluid. BP exposure was associated with reduced fertilization rates (P = .05). Obesity tended to lower live birth rates (P = .08) but did not affect embryo development or implantation. Age significantly impacted embryo quantity (P < .001) and quality (P = .03). GC progesterone secretion was correlated with donor age after exposure to 1 µM and 10 µM BPS (P = .03 for both). GCs from younger women appeared more sensitive to BPS. Conclusion:Although obesity did not affect embryonic development, its association with reduced live birth rates suggests a suboptimal environment for implantation and/or fetal development. Age was linked to lower antral follicle count, pregnancy rates, and live birth rates. Younger women's GCs may exhibit heightened sensitivity to BPS exposure, warranting further investigation.

Introduction: Cleft lip and/or palate (CLP) is frequently associated with persistent nasal obstruction, often due to structural deformities unaddressed by primary surgical repair. While subjective assessment tools are commonly used to evaluate nasal patency, they underestimate functional impairment, particularly nasal valve collapse. This study aims to objectively evaluate nasal obstruction and identify its anatomical causes in CLP patients after primary rhinoplasty. Methods: We conducted an observational study involving 21 children aged 8–16 with CLP who had undergone primary cheilorhinoplasty but not secondary nasal surgery. Each participant underwent clinical evaluation, nasal endoscopy, acoustic rhinometry, and active anterior rhinomanometry (AAR), both before and after nasal decongestion. The Nasal Obstruction Symptom Evaluation (NOSE) scale was used to assess subjective symptoms. Obstructive sites were diagnosed based on established criteria combining endoscopic and functional findings. Results: Objective nasal obstruction was identified in 80.9% of patients, with nasal valve collapse observed in 66.7%, most commonly among unilateral and bilateral CLP subtypes. External nasal valve collapse was the predominant form (57.1%), followed by internal valve involvement (38.1%). Notably, the NOSE score did not reliably correlate with the AAR results, underlining the limitations of subjective assessment tools. Structural anomalies such as septal deviation (52.5%) and turbinate hypertrophy (23.8%) were also prevalent. Conclusions: This study highlights nasal valve collapse as a major, underrecognized contributor to persistent nasal obstruction in CLP patients after primary repair. Objective assessment methods like AAR and targeted endoscopy should be routinely integrated into secondary rhinoplasty planning. These findings advocate for a personalized approach to secondary nasal reconstruction in CLP patients, integrating objective functional data into surgical planning. Such strategies align with personalized medicine principles by tailoring interventions to individual anatomical and physiological characteristics.

Background: The health crisis related to the COVID-19 pandemic led to an unprecedented situation in France: complete lockdown. The population had to live confined with their families, which often meant that parents telecommuted while caring for their children. However, daily risks remained more than ever at the forefront. The aim of this study was to assess the epidemiology of burns among children during three different periods of family time: school time, vacation, and lockdown. Methods: A single -center retrospective study was conducted at Tours University Hospital. All pediatric surgical emergency room visits recorded from February 10, 2020 to March 31, 2020 were included. The three aforementioned periods were assessed. Results: During lockdown there were significantly more burns compared to other injuries (p = 0.004). Preschool -age children suffered significantly more from burns during the same period (p = 0.029). There were no significant differences for nursery school (p = 0.522), primary school (p = 0.519), middle school (p = 0.613), and high school (p = N) children. Conclusion: This study underlines the need to establish a targeted prevention campaign geared toward a complicated geopolitical situation a pandemic that might occur again. (c) 2023 French Society of Pediatrics. Published by Elsevier Masson SAS. All rights reserved.

Bisphenol S (BPS) is the main substitute for bisphenol A (BPA), a well-known plasticiser and endocrine disruptor. BPS disrupts ovarian function in several species. Moreover, a few studies have reported that the effects of BPS might be modulated by the metabolic status, and none have characterised the granulosa cell (GC) proteome after chronic BPS exposure. This study aimed to decipher the mechanisms of action of chronic BPS exposure on the proteome of ewe GCs while considering the interaction between a deliberate contrasted metabolism and reproductive function. Forty ewes were split into two groups with contrasted diets: restricted (R, n = 20) and well-fed (WF, n = 20). The R and WF ewes were subdivided according to the dose of BPS administered through the diet (0–50 µg/kg/day), forming four groups: R0, R50, WF0 and WF50. After 3-month BPS daily exposure, GCs were recovered during the pre-ovulatory stage and proteins were analysed by nano-liquid chromatography coupled with tandem mass spectrometry. Chronic exposure to BPS affected the GC proteome differently according to the ewe metabolic status. Fifty-nine out of 958 quantified proteins were differentially abundant between groups and are mainly involved in carbohydrate and lipid pathways. Unsupervised hierarchical clustering of differentially abundant proteins (DAPs) identified four clusters of 34, 6, 5 and 14 proteins according to the BPS exposure and diet interaction. Pairwise comparisons between groups also revealed a strong effect of BPS exposure and diet interaction. Functional analysis of DAPs highlighted that BPS upregulated β-glucuronidase (GUSB; p = 0.002), a protein especially able to deconjugate bisphenol glucuronides (BP-g). Moreover, among unexposed ewes, GUSB was detected only in well-fed ewes. Conjugation of glucuronides inhibits the oestrogenic activity of bisphenols. Upregulation of GUSB in ewes dosed with BPS would prolong the oestrogenic effects of BPS by deconjugating BPS-g into free BPS. In addition, literature has reported an up-regulation of GUSB in people suffering from obesity. Therefore, people suffering from obesity could be subjected to prolonged and aggravated exposure to BPS. These data highlighted the deleterious effects of BPS and its interaction with metabolic status.

Total nephrectomies for the treatment of Wilms’ tumor (WT) are more and more performed by laparoscopy, although indications for this approach following the UMBRELLA guidelines are currently very restrictive. The purpose of this study was to assess the compliance to the criteria of the UMBRELLA protocol for minimally invasive approach of WT. This retrospective multicenter study included children operated on by laparoscopic total nephrectomy for suspected WT before 2020. Imaging was reviewed centrally. Fifty-six patients (50 WT and 6 nephrogenic rests) were operated on at a median age of 3.3 ± 2.6 years. Thirteen (23

Abstract Background Ovarian granulosa cells (GC) are essential for the development and maturation of a proper oocyte. GC are sensitive to endocrine disruptors, including bisphenol A (BPA) and its analogue bisphenol S (BPS), plasticisers present in everyday consumer products. BPA exhibits greater binding affinity for the membrane oestrogen receptor (GPER) than for the nuclear oestrogen receptors (ERα and ERβ). Here, we analysed the effects of BPA and BPS on the steroidogenesis of ovine GC in vitro, as well as their early mechanisms of action, the ovine being a relevant model to study human reproductive impairment. Disruption of GC steroidogenesis might alter oocyte quality and consequently fertility rate. In addition, we compared the effects of a specific GPER agonist (G-1) and antagonist (G-15) to those of BPA and BPS. Ewe GC were cultured with BPA or BPS (10 or 50 µM) or G-1 (1 µM) and/or G-15 (10 µM) for 48 h to study steroidogenesis. Results Both BPA and BPS (10 µM) altered the secretion of progesterone, however, only BPS (10 µM) affected oestradiol secretion. RNA-seq was performed on GC after 1 h of culture with BPA or BPS (50 µM) or G-1 (10 µM), followed by real-time PCR analyses of differentially expressed genes after 12, 24 and 48 h of culture. The absence of induced GPER target genes showed that BPA and BPS did not activate GPER in GC after 1 h of treatment. These molecules exhibited mainly independent early mechanisms of action. Gene ontology analysis showed that after 1 h of treatment, BPA mainly disrupted the expression of the genes involved in metabolism and transcription, while BPS had a smaller effect and impaired cellular communications. BPA had a transient effect on the expression of CHAC1 (NOTCH signalling and oxidative balance), JUN (linked to MAPK pathway), NR4A1 (oestradiol secretion inhibition), ARRDC4 (endocytose of GPCR) and KLF10 (cell growth, differentiation and apoptosis), while expression changes were maintained over time for the genes LSMEM1 (linked to MAPK pathway), TXNIP (oxidative stress) and LIF (cell cycle regulation) after 12 and 48 h, respectively. Conclusion In conclusion, although they exhibited similar effects, BPA and BPS impaired different molecular pathways in GC in vitro. New investigations will be necessary to follow the temporal changes of these genes over time, as well as the biological processes involved.

Abstract Introduction Objective structured clinical examinations (OSCEs) have been introduced with the stated objective of assessing the clinical skills acquired by students during internships. Our objective was to assess whether the scores obtained during the summative OSCEs of medical students are associated with having completed an internship in the corresponding disciplines. Methods Cross-sectional study assessing the results of the summative OSCEs during the 2021–2022 academic year in Poitiers university (France). Ten stations (5 for each student) were performed. A survey was carried out at the end of the OSCEs and collected: internships carried out, stress level, difficulty level experienced at each station, previous participation to formative and summative OSCEs, supervised clinical examinations during internships and participation in consultations. Results Out of the 220 students participating to the summative OSCEs, 182 (83%) answered the survey. The scores obtained in interrogation, communication, therapeutic education and procedure stations were higher when the student had completed an internship in the corresponding disciplines than if he had not (p < 0.01 for each). Eighty-seven (47.8%) had participated before to at least one formative OSCE and 145 (79.7%) to at least one summative OSCE. There was no significant difference in the overall OSCE score according to earlier participation to formative OSCEs (11.1 ± 1.9 vs. 11.5 ± 2.1, p = 0.16) or summative OSCEs (11.4 ± 2.1 vs. 11.1 ± 1.67, p = 0.47). Conclusion Success in OSCEs was associated with previous internships in the corresponding disciplines, suggesting the ability of OSCEs to assess the student’s clinical skills acquired during internships.

Slow-flow vascular malformations (VMs), especially those with venous components, can be complicated by localized intravascular coagulopathy (LIC), responsible for pain and impaired quality of life. Several studies have shown the effectiveness of mTOR inhibitors (especially sirolimus) on slow-flow VMs but its effect on coagulation has been poorly studied, especially in children. Our study shows that venous and combined VMs are associated with coagulation abnormalities and provides novel evidence that sirolimus improves coagulopathy in venous malformations. However we did not clearly evidence predictive biomarkers of response to sirolimus but this is the first study attempting to highlight predictive markers of response to sirolimus.

Bisphenol (BP) structural analogues of BPA are widely used. Previous studies showed similar effects of BPA and BPS on reproduction in several species including human. We hypothesised that the similar effects of several bisphenols (BPs) could accumulate in granulosa cells (GCs) and affects steroidogenesis. This study investigated the effects of seven BP analogues and their equimolar cocktail on human granulosa cells (hGC) and assessed BPA, BPS, BPF and BPAF level exposures in the follicular fluid of 277 women undergoing Assisted Reproductive Technology. The hGCs were recovered after women oocyte punctures and treated with the seven BP analogues (BPS, BPA, BPAF, BPF, BPAP, BPE and BPB) or their equimolar cocktail of 7 × 1.43 or 7 × 7.14 μM for each of the seven BPs, the sum of BPs reaching 10 ("∑BPs 10 μM"), or 50 μM ("∑BPs 50 μM"), respectively. Oestradiol and progesterone secretion, cell proliferation, viability and expression of steroidogenic enzymes were investigated. Progesterone secretion was decreased by 6 BPs 10 μM and the cocktail "∑BPs 10 μM", (-17.8 to -41.3%) and by all seven BPs 50 μM and "∑BPs 50 μM" (-21.8 to -84.2%). Oestradiol secretion was decreased only by 50 μM BPAF and BPAP (-37.8% and -44%, respectively), with corresponding decreases in CYP17A1 and CYP19A1 gene expression. Cellular proliferation was decreased after treatment with 50 μM BPAF (-32.2%), BPAP (-29%), BPB (-24%) and the equimolar cocktail "∑BPs 50 μM" (-33.1%). BPB (50 μM) and the cocktail "∑BPs 50 μM" increased HSD3B2 mRNA expression. At least one BP was detected in 64 of 277 (23.1%) women follicular fluids. Similar effects of the seven BPs or their cocktail were observed on progesterone secretion and/or on cell proliferation, suggesting cumulative effects of BPs. Our results highlight the urge to consider all BPs simultaneously and to further investigate the potential additive or synergistic effects of several BPs.

Les malformations vasculaires (MVs) sont classées en fonction du type de vaisseau atteint et de leur flux hémodynamique : on distingue les MVs à flux rapide et les MVs à flux lent. Les MVs à flux lent et particulièrement les malformations veineuses peuvent se compliquer de thromboses secondaires à une coagulation intravasculaire locale (CIL) pouvant être responsable de douleurs et altérer la qualité de vie des patients. Plusieurs études ont montré une efficacité des inhibiteurs de mTOR sur les symptômes liés aux MVs à flux lent. L'objectif de notre étude a été de mesurer et comparer les taux sanguins des facteurs de croissance de l'endothélium vasculaire A et C (VEGF-A, VEGF-C), du facteur tissulaire et des marqueurs de la coagulation (plaquettes, fibrinogène, D-dimères et facteur V) chez des enfants atteints de MVs à flux lent, avant et après traitement par sirolimus, afin d'évaluer un éventuel impact du sirolimus sur les marqueurs et de déterminer si ces biomarqueurs sont prédictifs de la réponse au traitement. Les échantillons sanguins ont été prélevés chez 59 enfants âgés de 6 à 18 ans, inclus dans l'étude multicentrique de phase II PERFORMUS qui étudiait l'efficacité et la sécurité du sirolimus chez les enfants atteints de MVs compliquées à flux lent. Les échantillons analysés ont été prélevés à au moins 2 moments : au début de l'étude (M0) et à la fin du traitement par sirolimus (M12). Au début de l'étude, le fibrinogène et le facteur V étaient significativement plus bas dans les malformations veineuses et veino-lymphatiques que dans les malformations lymphatiques kystiques (bien que les valeurs aient été normales) et les D-dimères étaient significativement augmentés (> 1000 ng/mL). Sous sirolimus, nous avons observé une augmentation du facteur V, du fibrinogène et du VEGF-A dans les malformations veineuses. Une augmentation du fibrinogène et du facteur V étaient associées de façon variable (selon les groupes de MVs) à une bonne réponse au sirolimus, même si les taux restaient dans la norme. Par ailleurs, les taux plasmatiques de VEGF-A ont augmenté significativement sous sirolimus chez les enfants atteints de malformations veineuses. Notre étude montre que chez les enfants aussi, la CIL est associée aux malformations veineuses et veino-lymphatiques et que le sirolimus améliore la CIL dans les malformations veineuses. Il y a peu de données sur les marqueurs de la coagulation chez les enfants porteurs de MVs. Deux études portant sur 24 et 62 enfants atteints de MVs veineuses ont rapporté des D-dimères élevés dans 33 % et 39 % des cas respectivement. Un seul patient avait un faible taux de fibrinogène et les taux de plaquettes étaient normaux. La proportion de patients présentant une augmentation des D-dimères dans les MVs veineuses était plus élevée dans notre étude (81,8 %). Nous n'avons pas clairement identifié de biomarqueurs prédictifs de réponse au sirolimus dans cette étude. Toutefois, celle-ci était limitée par le faible nombre de prélèvements dans l'analyse des marqueurs biologiques.

Bisphenol S (BPS) affects terminal folliculogenesis by impairing steroidogenesis in granulosa cells from different species. Nevertheless, limited data are available on its effects during basal folliculogenesis. In this study, we evaluate in vitro the effects of a long-term BPS exposure on a model of basal follicular development in a mono-ovulatory species. We cultured ovine preantral follicles (180–240 μm, n = 168) with BPS (0.1 μM (possible human exposure dose) or 10 μM (high dose)) and monitored antrum appearance and follicular survival and growth for 15 days. We measured hormonal secretions (oestradiol (at day 13 [D13]), progesterone and anti-Müllerian hormone [D15]) and expression of key follicular development and redox status genes (D15) in medium and whole follicles, respectively. BPS (0.1 µM) decreased oestradiol secretion compared with the control (−48.8%, p < 0.001), without significantly impairing antrum appearance, follicular survival and growth, anti-Müllerian hormone and progesterone secretion and target gene expression. Thus, BPS could also impair oestradiol secretion during basal folliculogenesis as it is the case during terminal folliculogenesis. It questions the use of BPS as a safe BPA substitute in the human environment. More studies are required to elucidate mechanisms of action of BPS and its effects throughout basal follicular development.

Abstract Introduction There have been numerous reports of robotic pediatric surgery in the literature, particularly regarding urological procedures for school-aged children. Thoracic procedures appear to be less common, despite the fact that encouraging results were reported more than 10 years. Our aim was to report a national experience of esophageal robotic-assisted thoracoscopic surgery (ERATS) and to discuss the most appropriate indications. Materials and Methods A retrospective multicenter study was conducted to compile the ERATS performed at five French surgical centers that have been involved in spearheading robotic pediatric surgery over the past 15 years. The data were supplemented by a review of the literature. Results Over the study period, 68 cases of robotic thoracic surgery were performed at the five pediatric centers in question. ERATS was performed for 18 patients (mean age 7.1 years [ ± 5.6]) in four of the centers. These comprised seven esophageal duplications, four esophageal atresias, five Heller's myotomies, and two cases of esophagoplasty. A conversion was needed for two neonates (11%) due to exposure difficulties. Four other procedures for patients who weighed less than 15 kg were successfully completed without causing postoperative complications. In the past 12 years, 22 other cases of ERATS were published worldwide. The indications were the same, except for esophagoplasty, which was not found. Conclusion Aside from accessibility issues with the robotic platform, the main limitation is still very much that the low body weight of children results in incompatibility between the size of the trocars and the size of the intercostal space. ERATS is clearly a feasible procedure with technical advantages for most pediatric cases with body weights more than 15 kg. A transdiaphragmatic abdominal approach should be considered for lower esophagus surgery.

Bisphenol A (BPA), an endocrine disruptor, has been replaced by structural analogues including bisphenol S (BPS). BPA and BPS exhibited similar effects regarding reproductive functions. Moreover, metabolic status and lipid metabolism are related to female fertility and could worsen BPS effects. The objective was to determine BPS in vivo effects on folliculogenesis and embryo production after chronic exposure through diet, and the influence of metabolic status in adult ewes. Sixty primiparous 2.5 year-old ewes, undergoing a restricted or well fed diet, were exposed to BPS (0, 4 or 50 mu g/kg/day) for at least three months. After hormonal oestrus synchronisation and ovarian stimulation, ewes were subjected to ovum pick-up (OPU) procedures to collect immature oocytes, that underwent in vitro maturation, fertilisation and embryo production. Body weight, body condition score and plasma glucose were higher in well-fed compared to restricted ewes, while plasma NEFA was lower during the 4-5 months after the beginning of the diets. Plasma progesterone levels increased on day 5 before OPU session in well-fed compared to restricted ewes. No effect of BPS dose was observed on follicle population, plasma AMH levels and embryo production numbers and rates. However, a significant diet x BPS dose interaction was reported for cleaved embryos, > 4-cell embryos, blastocyst and early blastocyst numbers, and plasma triiodothyronine levels. Our study showed that a contrasted diet did not affect follicle population nor embryo production in adult ewes but could affect the quality and progesterone secretion of the corpus luteum. Chronic low BPS exposure had no effect on follicular population and oocyte competence. Nevertheless, the significant diet x dose interactions observed on embryo production suggest that BPS effect is modulated by metabolic status. Further studies are required to assess the risk of BPS exposure for public reproductive health.