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Background and Objective: This study aimed to explore the impact of positive or negative feedback on the performance of trainees in pediatric urology during simulation exercises in pediatric laparoscopy., Methods: Twenty-five students enrolled in a national Pediatric Urology Laparoscopy Simulation participated in the study. They performed the Fundamentals of Laparoscopic Surgery (FLS) skills, specifically peg-transfer and intracorporeal knot-tying, in a randomized study design while receiving positive or negative feedback from an attending pediatric urologist. On the first day, all students performed FLS peg-transfer and intracorporeal knot-tying tasks on a pediatric laparoscopic simulator. On the second day, students were randomized to receive either positive or negative comments during the procedure. Task performances, measured by task time and errors, was compared between both groups. Statistical analysis was conducted using the Mann-Whitney U test., Key Findings and Limitations: The difference in execution time between exercises with and without feedback was significantly greater in the group that received negative feedback compared to the group that received positive feedback (p = 0.003). Students who received positive feedback increased their time by a median of 2 s, whereas students who received negative comments increased their time by a median of 34 s., Conclusions and Clinical Implications: Feedback should be delivered in a manner that is supportive, respectful, and improvement-focused rather than discouragement. Understanding these dynamics can guide the development of effective feedback strategies to optimize learning and enhance performance outcomes in training for minimally invasive surgery in pediatric urology., Competing Interests: Conflict of interest The authors certify that there is no conflict of interest with any financial organization regarding the material discussed in the manuscript., (Copyright © 2025 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.)

Background: Endoscopic injection (EI) is a safe treatment for vesico-ureteral reflux (VUR) in children, but recurrences are not insignificant. This study aims to show if multiple EI is still the best first line management even if in case of recurrences., Methods: All patients affected by primary VUR, treated with at least one EI and with at least 5 years follow up were included. All general data were analyzed. Recurrence rate after one, two and three EIs were calculated., Results: One hundred and sixty-one patients (total number =210) were healed after 1 injection, 28 after 2 and 4 after 3 with a global success rate of 91.90%. Recurrence rate is higher in patients older than 3 years old and with IV and V reflux grade. Even if 67.7% of recurrent VUR after one injection was symptomatic, diagnosis of recurrences after multiple EI was mainly radiological. Only 8% of the patients underwent EI need an anti-reflux surgery., Conclusions: Thanks to its low costs and the acceptable recurrence rate, Deflux EI should be proposed as the first therapeutic approach for children affected by VUR, especially in those with low and moderate grades of VUR. Multiple injections could be contraindicated only in older children thank 1 year with high-grade VUR (IV symptomatic and V grade)., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tau.amegroups.com/article/view/10.21037/tau-24-76/coif). The authors have no conflicts of interest to declare., (2024 Translational Andrology and Urology. All rights reserved.)

Purpose: Surgical management of ovarian masses in girls still challenging. The aim of the study is to report an 8-year experience in managing children with ovarian masses, and to demonstrate the advantages and the limitations of laparoscopy for such lesions., Methods: Data of girls aged less than 18 years operated because of an ovarian mass between January 2015 and February 2023 were retrospectively reviewed. Patients were divided into two groups: group A including children operated by laparoscopy, and Group B of patients who underwent open surgery., Results: Eighty-eight children were enrolled. Laparoscopy was performed in 56 patients (63.6%). Group A patients had smaller tumor size (53.6±38.5 vs. 122.2±75.4 mm, P<0.0001), shorter operative time (50.4±20.3 vs. 71.5±36.5 min, P = 0.004), reduced length of hospital stay (1.4±1.1 vs. 3±2.3 days, P<0.0001), and absence of postoperative complications. Only 3 cases (5.7%) of recurrence were seen exclusively within patients followed for benign tumors during a mean follow-up period of 4.6±3 years., Conclusion: Laparoscopy should be done in benign ovarian lesions or/and if a torsion is seen. For tumors at high risk of malignancy, laparoscopy can be performed to establish a clear macroscopic diagnosis, for staging of the disease, and resection of small tumors. Conversion to open surgery is indicated in case of doubt., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objectives: To assess the efficacy of thoracoscopy and the outcome for children with thoracic neurogenic tumors., Methods: We performed a retrospective review of 15 European centers between 2000 and 2020 with patients who underwent thoracoscopy for a neurogenic mediastinal tumor. We assessed preoperative data, complications, and outcomes. Results were expressed with the median and range values., Results: We identified 119 patients with a median age of 4 years old (3 months-17 years). The diameter was 5.7 cm (1.1-15). INRG stage was L1 n = 46, L2 n = 56, MS n = 5, M n = 12. Of 69 patients with image-defined risk factors (IDRF), 29 had only (T9-T12) locations. Twenty-three out of 34 patients with preoperative chemotherapy had an 18 mm (7-24) decrease in diameter. Seven out of 31 patients lost their IDRF after chemotherapy. Fourteen had a conversion to thoracotomy. The length of the hospital stay was 4 days (0-46). The main complications included chylothorax ( n = 7) and pneumothorax ( n = 5). Long-term complications included Horner's syndrome ( n = 5), back pain, and scoliosis ( n = 5). Pathology was 53 neuroblastomas, 36 ganglioneuromas, and 30 ganglioneuroblastomas. Fourteen had a postoperative residue. With a median follow-up of 21 months (4-195), 9 patients had a recurrence, and 5 died of disease. Relapses were associated with tumor biology, histology, and the need for chemotherapy ( p = 0.034, <0.001, and 0.015, respectively). Residues were associated with preoperative IDRF (excluding T9-T12 only) and the need for preoperative chemotherapy ( p = 0.04 and 0.020)., Conclusion: Our results show that thoracoscopy is safe, with good outcomes for thoracic neurogenic tumors in selected cases. Surgical outcomes are related to the IDRFs, whereas oncologic outcomes are related to tumor histology and biology.

Bioinspired adhesives have been increasingly developed, especially towards a biomedical application. Therefore, in this study, dopamine (DA) was oxidized into polydopamine (PDA) in a gelatin mixture via titration with NaIO 4 as a strong oxidant to easily obtain an adhesive antioxidant and self-healing PDA-gelatin hydrogel. Rheology experiments show a stiffness in the order of kPa and a thermal resistance above 50 °C, much above the gel-sol transition temperature of pristine gelatin. After heating at 55 °C, the gel is self-healing. In addition, just after formulation, it shows strong peeling-rate-dependent adhesion to steel with a tensile work per unit area ( W ) of up to 100 ± 39 J/m 2 , which is 2.5 times higher than that of the same gel without PDA at a peeling rate of 1000 µm/s. The increase in W between peeling rates of 10 and 1000 µm/s was studied and interpreted in terms of the gels' viscoelasticity. Moreover, this hydrogel offers significant antioxidant activity (measured by DPPH scavenging) that lasts with storage for at least over 15 days, this being then prolonged for 2 additional days, which seems particularly relevant considering the importance of reactive oxygen species (ROS) in wound healing. To summarize, PDA-gelatin gel is a promising strong and antioxidant adhesive.

Patient reported outcomes measures (PROMS) are important endpoints to measure patient health status in the perioperative setting. However, there are no good tools to measure PROMS in the pediatric surgical population. Patients 7 to 17 years old undergoing surgery were included and followed up for 1 day after surgery (POD1). At POD1 the patients were asked to rate their overall postoperative recovery using a 100-mm visual analog scale (VAS). The primary outcome was the pediatric QoR-15 score on postoperative day 1 (POD1). 150 patients completed the study. The mean (SD) pediatric QoR-15F scores were 132.1 (14.1) and 111.0 (27.0), preoperatively and on POD1, respectively. Convergent validity confirmed with Pearson (r) correlation between the postoperative pediatric QoR-15F and the patient-rated global recovery assessment was 0.72 (95% confidence interval [0.63-0.79]; p < 10 -16 ). Concerning reliability, internal consistency of the pediatric QoR-15 assessed by Cronbach's alpha was 0.90. The test-retest concordance correlation coefficient was 0.92; 95% CI [0.83-0.96]. Split-half alpha was 0.74. The pictorial pediatric version of the QoR-15F showed good validity, reliability, responsiveness, acceptability and feasibility. This PROMS should be considered for clinical care and research in the perioperative pediatric patient setting.Trial Registration: NCT04453410 on clinicaltrials.gov., (© 2023. Springer Nature Limited.)

In 2007, polydopamine (PDA) films were shown to be formed spontaneously on the surface of all known classes of materials by simply dipping those substrates in an aerated dopamine solution at pH = 8.5 in the presence of Tris(hydroxymethyl) amino methane buffer. This universal deposition method has raised a burst of interest in surface science, owing not only to the universality of this water based one pot deposition method but also to the ease of secondary modifications. Since then, PDA films and particles are shown to have applications in energy conversion, water remediation systems, and last but not least in bioscience. The deposition of PDA films from aerated dopamine solutions is however a slow and inefficient process at ambient temperature with most of the formed material being lost as a precipitate. This incited to explore the possibility to get PDA and related films based on other catecholamines, using other oxidants than dissolved oxygen and other deposition methods. Those alternatives to get PDA and related films are reviewed and compared in this paper. It will appear that many more investigations are required to get better insights in the relationships between the preparation method of PDA and the properties of the obtained coatings., (© 2023 Wiley-VCH GmbH.)

A hallmark of primate postimplantation embryogenesis is the specification of extraembryonic mesoderm (EXM) before gastrulation, in contrast to rodents where this tissue is formed only after gastrulation. Here, we discover that naive human pluripotent stem cells (hPSCs) are competent to differentiate into EXM cells (EXMCs). EXMCs are specified by inhibition of Nodal signaling and GSK3B, are maintained by mTOR and BMP4 signaling activity, and their transcriptome and epigenome closely resemble that of human and monkey embryo EXM. EXMCs are mesenchymal, can arise from an epiblast intermediate, and are capable of self-renewal. Thus, EXMCs arising via primate-specific specification between implantation and gastrulation can be modeled in vitro. We also find that most of the rare off-target cells within human blastoids formed by triple inhibition (Kagawa et al., 2021) correspond to EXMCs. Our study impacts our ability to model and study the molecular mechanisms of early human embryogenesis and related defects., Competing Interests: Declaration of interests The Institute for Molecular Biotechnology, Austrian Academy of Sciences has filed patent application EP21151455.9 describing the protocols for human blastoid formation. H.K. and N.R. are the inventors of this patent. All other authors declare no competing interests. J.R. is a member of the Cell Stem Cell advisory board., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

Objective: Despite recent progress in caring for patients born with esophageal atresia (EA), undernutrition and stunting remain common. Our study objective was to assess nutritional status in the first year after birth with EA and to identify factors associated with growth failure., Study Design: We conducted a population-based study of all infants born in France with EA between 2010 and 2016. Through the national EA register, we collected prenatal to 1 year follow-up data. We used body mass index and length-for-age ratio Z scores to define patients who were undernourished and stunted, respectively. Factors with P < 0.20 in univariate analyses were retained in a logistic regression model., Results: Among 1,154 patients born with EA, body mass index and length-for-age ratio Z scores at 1 year were available for about 61%. Among these, 15.2% were undernourished and 19% were stunted at the age of 1 year. There was no significant catch-up between ages 6 months and 1 year. Patients born preterm (41%), small for gestational age (17%), or with associated abnormalities (55%) were at higher risk of undernutrition and stunting at age 1 year ( P < 0.05). Neither EA type nor surgical treatment was associated with growth failure., Conclusion: Undernutrition and stunting are common during the first year after birth in patients born with EA. These outcomes are significantly influenced by early factors, regardless of EA type or surgical management. Identifying high-risk patient groups with EA (i.e., those born preterm, small for gestational age, and/or with associated abnormalities) may guide early nutritional support strategies., 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 of interest., (Copyright © 2022 Depoortere, Lapillonne, Sfeir, Bonnard, Gelas, Panait, Rabattu, Guignot, Lamireau, Irtan, Habonimana, Breton, Fouquet, Allal, Elbaz, Talon, Ranke, Abely, Michel, Lirussi Borgnon, Buisson, Schmitt, Lardy, Petit, Chaussy, Borderon, Levard, Cremillieux, Tolg, Breaud, Jaby, Grossos, De Vries, Arnould, Pelatan, Geiss, Laplace, Kyheng, Nicolas, Aumar and Gottrand.)

Although central venous catheter (CVC)-related thrombosis (CRT) is a severe complication of home parenteral nutrition (HPN), the amount and quality of data in the diagnosis and management of CRT remain low. We aimed to describe current practices regarding CVC management in French adult and pediatric HPN centers, with a focus on CVC obstruction and CRT. Current practices regarding CVC management in patients on HPN were collected by an online-based cross-sectional survey sent to expert physicians of French HPN centers. We compared these practices to published guidelines and searched for differences between pediatric and adult HPN centers' practices. Finally, we examined the heterogeneity of practices in both pediatric and adult HPN centers. The survey was completed by 34 centers, including 21 pediatric and 13 adult centers. We found a considerable heterogeneity, especially in the responses of pediatric centers. On some points, the centers' responses differed from the current guidelines. We also found significant differences between practices in adult and pediatric centers. We conclude that the management of CVC and CRT in patients on HPN is a serious and complex situation for which there is significant heterogeneity between HPN centers. These findings highlight the need for more well-designed clinical trials in this field.

Human naive pluripotent stem cells have unrestricted lineage potential. Underpinning this property, naive cells are thought to lack chromatin-based lineage barriers. However, this assumption has not been tested. Here we define the chromatin-associated proteome, histone post-translational modifications and transcriptome of human naive and primed pluripotent stem cells. Our integrated analysis reveals differences in the relative abundance and activities of distinct chromatin modules. We identify a strong enrichment of polycomb repressive complex 2 (PRC2)-associated H3K27me3 in the chromatin of naive pluripotent stem cells and H3K27me3 enrichment at promoters of lineage-determining genes, including trophoblast regulators. PRC2 activity acts as a chromatin barrier restricting the differentiation of naive cells towards the trophoblast lineage, whereas inhibition of PRC2 promotes trophoblast-fate induction and cavity formation in human blastoids. Together, our results establish that human naive pluripotent stem cells are not epigenetically unrestricted, but instead possess chromatin mechanisms that oppose the induction of alternative cell fates., (© 2022. The Author(s).)

Background: Precise gene dosage of the X chromosomes is critical for normal development and cellular function. In mice, XX female somatic cells show transcriptional X chromosome upregulation of their single active X chromosome, while the other X chromosome is inactive. Moreover, the inactive X chromosome is reactivated during development in the inner cell mass and in germ cells through X chromosome reactivation, which can be studied in vitro by reprogramming of somatic cells to pluripotency. How chromatin processes and gene regulatory networks evolved to regulate X chromosome dosage in the somatic state and during X chromosome reactivation remains unclear., Results: Using genome-wide approaches, allele-specific ATAC-seq and single-cell RNA-seq, in female embryonic fibroblasts and during reprogramming to pluripotency, we show that chromatin accessibility on the upregulated mammalian active X chromosome is increased compared to autosomes. We further show that increased accessibility on the active X chromosome is erased by reprogramming, accompanied by erasure of transcriptional X chromosome upregulation and the loss of increased transcriptional burst frequency. In addition, we characterize gene regulatory networks during reprogramming and X chromosome reactivation, revealing changes in regulatory states. Our data show that ZFP42/REX1, a pluripotency-associated gene that evolved specifically in placental mammals, targets multiple X-linked genes, suggesting an evolutionary link between ZFP42/REX1, X chromosome reactivation, and pluripotency., Conclusions: Our data reveal the existence of intrinsic compensatory mechanisms that involve modulation of chromatin accessibility to counteract X-to-Autosome gene dosage imbalances caused by evolutionary or in vitro X chromosome loss and X chromosome inactivation in mammalian cells., (© 2021. The Author(s).)

Background and Objectives: Respiratory diseases are common in children with esophageal atresia (EA), leading to increased morbidity and mortality in the first year. The primary study objective was to identify the factors associated with readmissions for respiratory causes in the first year in EA children., Methods: A population-based study. We included all children born between 2008 and 2016 with available data and analyzed factors at birth and 1 year follow-up. Factors with a P value <.10 in univariate analyses were retained in logistic regression models., Results: Among 1460 patients born with EA, 97 (7%) were deceased before the age of 1 year, and follow-up data were available for 1287 patients, who constituted our study population. EAs were Ladd classification type III or IV in 89%, preterm birth was observed in 38%, and associated malformations were observed in 52%. Collectively, 61% were readmitted after initial discharge in the first year, 31% for a respiratory cause. Among these, respiratory infections occurred in 64%, and 35% received a respiratory treatment. In logistic regression models, factors associated with readmission for a respiratory cause were recurrence of tracheoesophageal fistula, aortopexy, antireflux surgery, and tube feeding; factors associated with respiratory treatment were male sex and laryngeal cleft., Conclusions: Respiratory morbidity in the first year after EA repair is frequent, accounting for >50% of readmissions. Identifying high risk groups of EA patients (ie, those with chronic aspiration, anomalies of the respiratory tract, and need for tube feeding) may guide follow-up strategies., Competing Interests: POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose., (Copyright © 2021 by the American Academy of Pediatrics.)

Objective: To identify the risk factors for early mortality and morbidity in a population with distal esophageal atresia (EA)-tracheoesophageal fistula., Study Design: Cohort study from a national register. Main outcomes and measures included early mortality, hospital length of stay (LoS), need for nutritional support at 1 year of age as a proxy measure of morbidity, and complications during the first year of life., Results: In total, 1008 patients with a lower esophageal fistula were included from January 1, 2008, to December 31, 2014. The survival rate at 3 months was 94.9%. The cumulative hospital LoS was 31.0 (17.0-64.0) days. Multivariate analysis showed that intrahospital mortality at 3 months was associated with low birth weight (OR 0.52, 95% CI [0.38-0.72], P < .001), associated cardiac abnormalities (OR 6.09 [1.96-18.89], P = .002), and prenatal diagnosis (OR 2.96 [1.08-8.08], P = .034). LoS was associated with low birth weight (-0.225 ± 0.035, P < .001), associated malformations (0.082 ± 0.118, P < .001), surgical difficulties (0.270 ± 0.107, P < .001), and complications (0.535 ± 0.099, P < .001) during the first year of life. Predictive factors for dependency on nutrition support at 1 year of age were complications before 1 year (OR 3.28 [1.23-8.76], P < .02) and initial hospital LoS (OR 1.96 [1.15-3.33], P < .01)., Conclusions: EA has a low rate of early mortality, but morbidity is high during the first year of life. Identifying factors associated with morbidity may help to improve neonatal care of this population., (Copyright © 2021 Elsevier Inc. All rights reserved.)

To date, there is no representative in vitro model for liver sinusoidal endothelial cells (LSECs), as primary LSECs dedifferentiate very fast in culture and no combination of cytokines or growth factors can induce an LSEC fate in (pluripotent stem cell (PSC)-derived) endothelial cells (ECs). Furthermore, the transcriptional programmes driving an LSEC fate have not yet been described. Here, we first present a computational workflow (CenTFinder) that can identify transcription factors (TFs) that are crucial for modulating pathways involved in cell lineage specification. Using CenTFinder, we identified several novel LSEC-specific protein markers, such as FCN2 and FCN3, which were validated by analysis of previously published single-cell RNAseq data. We also identified PU.1 (encoded by the SPI1 gene) as a major regulator of LSEC-specific immune functions. We show that SPI1 overexpression (combined with the general EC TF ETV2) in human PSCs induces ECs with an LSEC-like phenotype. The ETV2-SPI1-ECs display increased expression of LSEC markers, such as CD32B and MRC1, as well as several of the proposed novel markers. More importantly, ETV2-SPI1-ECs acquire LSEC functions, including uptake of FSA-FITC, as well as labelled IgG. In conclusion, we present the CenTFinder computational tool to identify key regulatory TFs within specific pathways, in this work pathways of lineage specification, and we demonstrate its use by the identification and validation of PU.1 as a master regulator for LSEC fating.

Totipotency is the ability of a single cell to give rise to all of the differentiated cell types that build the conceptus, yet how to capture this property in vitro remains incompletely understood. Defining totipotency relies on a variety of assays of variable stringency. Here, we describe criteria to define totipotency. We explain how distinct criteria of increasing stringency can be used to judge totipotency by evaluating candidate totipotent cell types in mice, including early blastomeres and expanded or extended pluripotent stem cells. Our data challenge the notion that expanded or extended pluripotent states harbour increased totipotent potential relative to conventional embryonic stem cells under in vitro and in vivo conditions.

Background: The diaphragm, which forms a physical barrier between the thoracic and the abdominal cavities, is also the major part of the respiratory system. Congenital diaphragmatic hernia (CDH) is a malformation of that partition muscle. Expanded polytetrafluoroethylene (e-PTFE), a synthetic nondegradable biomaterial, is currently used for the repair of diaphragm defects. Indeed, this hydrophobic biomaterial does not promote rapid and dense cell colonization. Surface modifications are needed to favor or even guide cellular responses., Materials and Methods: In this context, we present here a practical and effective way of functionalization of the e-PTFE material. We investigated, by using electron microscopy, the coating with PRF (Platelet-Rich Fibrin) of PDA (Polydopamine) treated e-PTFE implant material., Results: We demonstrate that this straightforward chemical functionalization with PDA increases the hydrophilicity of e-PTFE and thus improves tissue integration. Then, we demonstrated that whatever the contact time between PRF and e-PTFE and the centrifugation speed, the PDA coating on the e-PTFE biomaterial promotes further biological events like cell adhesion and spreading., Conclusions: Our findings clearly show that this composite coating (chemically by using PDA + biologically by using PRF) method of e-PTFE is a simple, interesting and promising way to favor tissular integration of such biomaterials., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Objective: This multicentric study aimed to evaluate the quality of life (QOL) in children with Hirschsprung's disease (HD)., Methods: HD patients aged from 6 to 18 years and followed-up in 2 French pediatric surgery centers were included in this study. QOL was assessed using the HAQL questionnaires according to age (6-11 and 12-18), filled by patients and their parents (proxy reports) and correlated with initial disease characteristics, nutritional status, and functional score of Krickenbeck., Results: Sixty-three patients were included. The acquisition of satisfactory voluntary bowel movements was found in only 50% of the 6 to 11 years old and 68% of the teenagers. Seventy percentage of the children and 55% of teenagers had soiling issues. The overall HAQLproxy6--11 score was 528/700; best scores were found for "fecal continence" (94/100), "social functioning" (94/100), and "urinary continence" (92/100) whereas the worst scores were for "general well-being" (64/100) and "diurnal fecal continence" (58/100). The overall HAQLproxy12--16 score was 607/700; best scores were for "urinary continence" (96/100) and "social functioning" (93/100). In a multivariate analysis, soiling was the only factor significantly associated with low QOL (P = 0.03)., Conclusions: Soiling remains frequent in children operated on for HD and negatively affects their QOL. Assessment and treatment of soiling should be the priority for medical teams in the follow-up of these children.

Background: Over the past decade, laparoscopic hernia repair was the most performed operation in our department. Equally, it compromises 15% of all pediatric operations performed. We aim, in this study, to review all the cases performed and extrapolate important information like reoccurrences, the incidence of metachronous inguinal hernia, complications amongst other information., Material and Methods: All patients under the age of 18 whom underwent elective laparoscopic hernia repair between 03/01/2007 till the 18/05/2016 were included in our study. We recorded important clinical features and studied their post-operative follow up. Equally reoccurrences, the incidence of metachronous inguinal hernia, complications and other parameters were recorded and studied., Results: A total of 916 patients were operated on during the defined study period. There was a 0.17% reoccurrence rate and a 0.46% incidence of metachronous inguinal hernia. Equally a contralateral patent processus vaginalis was diagnosed and closed in 17.10%. There were no postoperative complications and we had a 0% postoperative hydrocele rate., Conclusion: Laparoscopic hernia repair is safe and carries all the benefits of minimally invasive surgery. We recommend that it is offered to patients and would like to refute previously claimed reports that it carries a higher reoccurrence rate or takes a long time to perform. Our reoccurrence rate of 0.17% is actually lower than many published reoccurrence rates after open repair., Competing Interests: There are no conflicts of interest., (Copyright: © 2019 Journal of Indian Association of Pediatric Surgeons.)

Reprogramming to induced pluripotency induces the switch of somatic cell identity to induced pluripotent stem cells (iPSCs). However, the mediators and mechanisms of reprogramming remain largely unclear. To elucidate the mediators and mechanisms of reprogramming, we used a siRNA-mediated knockdown approach for selected candidate genes during the conversion of somatic cells into iPSCs. We identified Tox4 as a novel factor that modulates cell fate through an assay that determined the efficiency of iPSC reprogramming. We found that Tox4 is needed early in reprogramming to efficiently generate early reprogramming intermediates, irrespective of the reprogramming conditions used. Tox4 enables proper exogenous reprogramming factor expression, and the closing and opening of putative somatic and pluripotency enhancers early during reprogramming, respectively. We show that the TOX4 protein assembles into a high molecular form. Moreover, Tox4 is also required for the efficient conversion of fibroblasts towards the neuronal fate, suggesting a broader role of Tox4 in modulating cell fate. Our study reveals Tox4 as a novel transcriptional modulator of cell fate that mediates reprogramming from the somatic state to the pluripotent and neuronal fate.This article has an associated First Person interview with the first author of the paper., Competing Interests: Competing interestsThe authors declare no competing or financial interests., (© 2019. Published by The Company of Biologists Ltd.)

Induction and reversal of chromatin silencing is critical for successful development, tissue homeostasis, and the derivation of induced pluripotent stem cells (iPSCs). X-Chromosome inactivation (XCI) and reactivation (XCR) in female cells represent chromosome-wide transitions between active and inactive chromatin states. Although XCI has long been studied, providing important insights into gene regulation, the dynamics and mechanisms underlying the reversal of stable chromatin silencing of X-linked genes are much less understood. Here, we use allele-specific transcriptomics to study XCR during mouse iPSC reprogramming in order to elucidate the timing and mechanisms of chromosome-wide reversal of gene silencing. We show that XCR is hierarchical, with subsets of genes reactivating early, late, and very late during reprogramming. Early genes are activated before the onset of late pluripotency genes activation. Early genes are located genomically closer to genes that escape XCI, unlike genes reactivating late. Early genes also show increased pluripotency transcription factor (TF) binding. We also reveal that histone deacetylases (HDACs) restrict XCR in reprogramming intermediates and that the severe hypoacetylation state of the inactive X Chromosome (Xi) persists until late reprogramming stages. Altogether, these results reveal the timing of transcriptional activation of monoallelically repressed genes during iPSC reprogramming, and suggest that allelic activation involves the combined action of chromatin topology, pluripotency TFs, and chromatin regulators. These findings are important for our understanding of gene silencing, maintenance of cell identity, reprogramming, and disease., (© 2019 Janiszewski et al.; Published by Cold Spring Harbor Laboratory Press.)

Dosage compensation between XX female and XY male cells is achieved by a process known as X chromosome inactivation (XCI) in mammals. XCI is initiated early during development in female cells and is subsequently stably maintained in most somatic cells. Despite its stability, the robust transcriptional silencing of XCI is reversible, in the embryo and also in a number of reprogramming settings. Although XCI has been intensively studied, the dynamics, factors, and mechanisms of X chromosome reactivation (XCR) remain largely unknown. In this review, we discuss how new sequencing technologies and reprogramming approaches have enabled recent advances that revealed the timing of transcriptional activation during XCR. We also discuss the factors and chromatin features that might be important to understand the dynamics and mechanisms of the erasure of transcriptional gene silencing on the inactive X chromosome (Xi).

Among the different materials used as protheses for the treatment of Congenital Diaphragmatic Hernia, expanded polytetrafluoroethylene (e-PTFE) plays a leading role owing to its mechanical properties as explained in the first part of this review. However, this material is poorly cell adhesive, which is expected for its contact on the abdominal face, but should display specific tissue adhesion on its thoracic exposed faced. A side specific functionalization method is hence required. The deposition of a nanosized polydopamine film on PTFE is known to be possible but immersion of the e-PTFE membrane in an aerated dopamine solution leads to a functionalization not only on both faces of the membrane but also in its porous volume. The fact that polydopamine also forms at the water/air interface has allowed to transfer a polydopamine film on only one face of the e-PTFE membrane. The deposition method and applications of such Janus like membranes are reviewed in the second part of the review.

Background/purpose: To implement resident curriculum in France based on theoretical teaching and bed side training, the national council known as the "Collège Hospitalier et Universitaire de Chirurgie Pédiatrique" examined the relevance and feasibility of systematically introducing simulation program in the pediatric surgery resident training., Material and Methods: A national simulation training program was developed and took place in a 2-day session organized in 7 simulation centers in France. The program included technical (laparoscopic/suturing technique on low-fidelity models) and nontechnical (6 scenarios for standardized consultation, and a team work scenario based on errors prevention in the operative room) skills. Evaluation of the program (Likert scale from 1 (bad) to 5 (excellent) and notation on 20 points) concerned trainees and trainers., Results: 40 residents (95% of all pediatric surgery French residents) attended with a ratio of trainees/trainer of ½. The training objectives earned a score of 4.46/5. The pedagogical value of the seminar scored 4.7/5, teaching quality 17.95/20, and the overall seminar score was 17.35/20., Conclusion: This program, unique nationally, was assessed very favorably by the participating residents and by the involved trainers. To our knowledge, it represents the first mandatory national simulation training program included within a surgical training model., Level of Evidence: Level IV., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Reprogramming female mouse somatic cells into induced pluripotent stem cells (iPSCs) leads to X-chromosome reactivation. The extent to which increased X-chromosome dosage (X-dosage) in female iPSCs compared with male iPSCs leads to differences in the properties of iPSCs is still unclear. We show that chromatin accessibility in mouse iPSCs is modulated by X-dosage. Specific sets of transcriptional regulator motifs are enriched in chromatin with increased accessibility in XX or XY iPSCs. The transcriptome, growth and pluripotency exit are also modulated by X-dosage in iPSCs. To understand how increased X-dosage modulates the properties of mouse pluripotent stem cells, we used heterozygous deletions of the X-linked gene Dusp9. We show that X-dosage regulates the transcriptome, open chromatin landscape, growth, and pluripotency exit largely independently of global DNA methylation. Our results provide insights into how gene dosage modulates the epigenetic and genetic mechanisms that regulate cell identity., (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: The authors present a multicenter retrospective series of different benign rib lesions in children operated on using thoracoscopy., Materials and Methods: Between 2005 and 2015, 17 rib resections were performed thoracoscopically, in four French departments of pediatric surgery. Of these 17 cases, 13 exostoses, 2 endochondromas, 1 synostosis, and 1 Cyriax's syndrome were noted. Inclusion criteria were benign tumors or rib anomalies such as synostosis, in children younger than the age of 18 years, and thoracoscopy. Open surgery and malignant tumors were excluded. Thoracoscopy was put forward using one optical port as well as one or two operative ports., Results: Ten patients presented with chest pain, dyspnea, or unexplained cough. Six tumors were incidentally diagnosed. One patient presented with a chest wall deformation. Single-lung ventilation was required in 2 cases. In 1 case of endochondroma, a segmental rib resection was performed, leaving a part of the periosteum and the intercostal vessels and nerve. In this case, rib resection was performed using an endoscopic shaver drill system. As for the other cases, a simple resection of the tumor or of the bridge between two ribs (synostosis) was performed. In these cases, a Codman Kerrison laminectomy rongeur was used. There was no complication during or after surgery. Nevertheless, 2 years after surgery, pain did not disappear in 1 case, probably due to a definitive intercostal nerve damage., Conclusion: Benign rib lesions in children are rare. Thoracoscopy may be offered to reduce the functional deleterious consequences of an open surgery. It may be put forward especially in case of hereditary multiple exostoses where redo procedures may be required.

Congenital diaphragmatic hernia is a severe disease requiring diaphragm replacement mostly with expanded polytetrafluoroethylene. Unfortunately, the recurrence rate is high due to prosthesis failure with significant morbidity for the child. To provide a better understanding of the integration and possible failure processes of the biomaterial implanted in humans, we conducted electron microscopical and mechanical assessments on a prosthesis explant from a child with congenital diaphragmatic hernia presenting a recurrence. Our findings show a major penetration of connective tissue into the expanded polytetrafluoroethylene on the rough side, whereas the smooth side presents few tissue colonization. This penetration is more important in the central area (area A) with large collagen bundles and layers, in comparison to the peripheral areas without prosthesis failure (area B), where few extracellular matrix is produced. The connective tissue penetrates the prosthesis in depth. In contrast, the peripheral areas with prosthesis failure (area C) show very few cells and extracellular matrix, with an oriented organization in comparison to areas A and B. Obviously, the forces applied on the implanted material modulate the cellular behavior of the newly developed tissues. Atomic force microscopic measurements of the biomaterials' surfaces may explain some cellular behaviors according to areas with or without failure.

Background: Complex procedures for managing congenital abnormalities are reported to be feasible. However, neonatal videosurgery involves very specific physiologic constraints. This study evaluated the safety and complication rate of videosurgery during the first month of life and sought to determine both the risk factors of perioperative complications and the most recent trends in practice., Methods: From 1993 to 2005, 218 neonates (mean age, 16 days; weight, 3,386 g) from seven European university hospitals were enrolled in a retrospective study. The surgical indications for laparoscopy (n = 204) and thoracoscopy (n = 14) were congenital abnormalities or exploratory procedures., Results: Of the 16 surgical incidents that occurred (7.5%), mainly before 2001, 11 were minor (parietal hematoma, eventration). Three neonates had repeat surgery for incomplete treatment of pyloric stenosis. In two cases, the incidents were more threatening (duodenal wound, diaphragmatic artery injury), but without further consequences. No mortality is reported. The 26 anesthetic incidents (12%) that occurred during insufflation included desaturation (<80% despite 100% oxygen ventilation) (n = 8), transient hypotension requiring vascular expansion (n = 7), hypercapnia (>45 mmHg) (n = 5), hypothermia (<34.9 degrees C) (n = 4), and metabolic acidosis (n = 2). The insufflation had to be stopped in 7% of the cases (transiently in 9 cases, definitively in 6 cases). The significant risk factors for an incident (p < 0.05) were young age of the patient, low body temperature, thoracic insufflation, high pressure and flow of insufflation, and length of surgery., Conclusion: Despite advances in miniaturizing of instruments and growth in surgeons' experience, the morbidity of neonatal videosurgery is not negligible. A profile of the patient at risk for an insufflation-related incident emerged from this study and may help in the selection of neonates who will benefit most from these techniques in conditions of maximal safety.

Functional inactivation of the von Hippel-Lindau (VHL) tumor suppressor gene occurs in 40-80% of human conventional renal cell carcinomas (RCCs). We showed recently that VHL-deficient RCCs expressed large amounts of parathyroid hormone-related protein (PTHrP), and that PTHrP, acting through the PTH1 receptor (PTH1R), plays an essential role in tumor growth. We also showed that PTHrP expression is negatively regulated by the VHL gene products (pVHL). Our goal was to determine whether blocking the PTHrP/PTH1R system might be of therapeutic value against RCC, independent of VHL status and PTHrP expression levels. The antitumor activity of PTHrP neutralizing antibody and of PTH1R antagonist were evaluated in vitro and in vivo in a panel of human RCC lines expressing or not pVHL. PTHrP is upregulated compared with normal tubular cells. In vitro, tumor cell growth and viability was decreased by up to 80% by the antibody in all cell lines. These effects resulted from apoptosis. Exogenously added PTHrP had no effect on cell growth and viability, but reversed the inhibitory effects of the antibody. The growth inhibition was reproduced by a specific PTH1R antagonist in all cell lines. In vivo, the treatment of nude mice bearing the Caki-1 RCC tumor with the PTHrP antibody inhibited tumor growth by 80%, by inducing apoptosis. Proliferation and neovascularization were not affected by the antiserum. Anti-PTHrP treatment induced no side effects as assessed by animal weight and blood chemistries. Current therapeutic strategies are only marginally effective against metastatic RCC, and adverse effects are common. This study provides a rationale for evaluating the blockade of PTHrP signaling as therapy for human RCC in a clinical setting.

Background and Aim: Recent reports in literature have emphasized the clinical perception of reduced pain, postoperative morbidity, and dysfunction associated with thoracoscopic approach compared with standard thoracotomy. The authors describe a thoracoscopic approach and technical details for diaphragmatic eventration repair in children., Patients and Methods: Ten patients, 4 girls and 6 boys, 1 teenager (14 years old) and 9 children (age range, 6-41 months; average, 17 months), were operated for a diaphragmatic eventration in 3 different pediatric surgery teams, according to the same technique. Symptoms were recurrent infection (7 cases), dyspnea on exertion (2 cases), and a rib deformity (1 case). An elective thoracoscopy was performed, patient in a lateral decubitus. A low carbon dioxide insufflation allowed a lung collapse. Reduction of the eventration was made progressively when folding and plicating the diaphragm. Plication of the diaphragm was done with an interrupted suture (6 cases) or a running suture (4 cases). The procedure finished either with an exsufflation (4 cases) or a drain (6 cases)., Results: A conversion was necessary in 2 cases: 1 insufflation was not tolerated and 1 diaphragm, higher than the fifth space, reduced too much the operative field. Patients recovered between 2 and 4 days. Dyspnea disappeared immediately. Mean follow-up of 16 months could assess the clinical improvement in every patient., Discussion: Thoracoscopic conditions are quite different between a diaphragmatic hernia repair previously reported and an eventration. Concerning diaphragmatic hernias, reduction is easy, giving a large operative space for suturing the diaphragm. Concerning diaphragmatic eventrations, the lack of space remains important at the beginning of the procedure despite the insufflation into the pleural cavity. The operative ports must be high enough in the chest to allow a good mobility of the instruments. Chest drainage seems to be unnecessary., Conclusion: Diaphragmatic eventration repair by thoracoscopy is feasible, safe, and efficient in children. Above all, it avoids a thoracotomy. It improves the immediate postoperative results with a good respiratory function.

Testis tumors are uncommon in childhood, and they differ from adult tumors in terms of histology and frequency. Sertoli cell tumors appear in children before 1 year of age. They are more frequently benign, but because of the absence of specific signs of malignancy, treatment consists of radical orchiectomy, sometimes followed by radiotherapy or chemotherapy based on histologic analysis. Malignancy is confirmed by the presence of metastasis or many mitosis and anaplastic cells. Children must be followed for several years to be sure of the absence of relapse or progression. In the authors' hospital, of 13 testis tumors diagnosed since 1996, only 2 were Sertoli cell tumors. It would be helpful to have an algorithm for the management of testis tumors, outlining how to make the diagnosis of malignancy and which treatment and follow-up to pursue.

Study Objective: To evaluate prophylactic antibiotic practices in urological surgery in Franche-Comté., Material and Methods: Six urological surgery teams participated in data collection. Practices were evaluated in comparison with national guidelines by means of five questions: Did the surgical operation justify prophylactic antibiotics and was this treatment administered? Was the antibiotic selected that recommended by national guidelines? Was the total duration appropriate? Was the time of the first injection appropriate? Was the dosage appropriate? The Société Française d'Anesthésie et de Réanimation (SFAR) guidelines, revised in 1999, constituted the reference., Results: Of the 213 operations included in the study, 134 corresponded to Altemeier class 1 and 2 operations for which the SFAR has issued guidelines. The overall compliance rate was 22.6%. Among the 56 patients who did not receive the recommended molecule, 45 received a molecule with a broader spectrum of activity than that of the recommended molecule. The duration of prophylactic antibiotics was longer for 10 of the 11 patients in whom the duration of prophylaxis did not comply with guidelines. Finally, for more than one third of operations, the time of injection of the first dose was not optimal., Conclusion: This study demonstrated the high frequency of non-compliance with prophylactic antibiotic prescription guidelines in urological surgery in Franche-Comté. These guidelines must be reinforced and applied to ensure the efficacy of prophylactic antibiotics and to avoid the emergence of resistant strains.