Single-cell transcriptomics identifies aberrant glomerular angiogenic signalling in the early stages of WT1 kidney disease.

WT1 encodes a podocyte transcription factor whose variants can cause an untreatable glomerular disease in early childhood. Although WT1 regulates many podocyte genes, it is poorly understood which of them are initiators in disease and how they subsequently influence other cell-types in the glomerulus. We hypothesised that this could be resolved using single-cell RNA sequencing (scRNA-seq) and ligand-receptor analysis to profile glomerular cell-cell communication during the early stages of disease in mice harbouring an orthologous human mutation in WT1 (Wt1).

A Clinical-Grade Partially Decellularized Matrix for Tracheal Replacement: Validation In Vitro and In Vivo in a Porcine Model.

The management of extensive tracheal resection followed by circumferential replacement remains a surgical challenge. Numerous techniques are proposed with mixed results. Partial decellularization of the trachea with the removal of the mucosal and submucosal cells is a promising method, reducing immunogenicity while preserving the biomechanical properties of the final matrix.

Heterozygosity for loss-of-function variants in LZTR1 is associated with isolated multiple café-au-lait macules.

Purpose: Pathogenic LZTR1 variants cause schwannomatosis and dominant/recessive Noonan syndrome (NS). We aim to establish an association between heterozygous loss-of-function LZTR1 alleles and isolated multiple café-au-lait macules (CaLMs).

Methods: A total of 849 unrelated participants with multiple CaLMs, lacking pathogenic/likely pathogenic NF1 and SPRED1 variants, underwent RASopathy gene panel sequencing.

Epstein-Barr Virus-Associated Smooth Muscle Tumor After Kidney Transplantation: A French Multicenter Retrospective Study.

Background: Epstein-Barr virus (EBV) is a herpesvirus linked to nine different human tumors and lymphoproliferative disorders. Immunosuppression promotes EBV-driven malignancies. The most frequent EBV-induced malignancies are lymphomas and nasopharyngeal carcinoma.

Cellular mechanisms of acute rhabdomyolysis in inherited metabolic diseases.

Acute rhabdomyolysis (RM) constitutes a life-threatening emergency resulting from the (acute) breakdown of skeletal myofibers, characterized by a plasma creatine kinase (CK) level exceeding 1000 IU/L in response to a precipitating factor. Genetic predisposition, particularly inherited metabolic diseases, often underlie RM, contributing to recurrent episodes. Both sporadic and congenital forms of RM share common triggers.

Word of caution: early life-threatening complication linked to pulmonary flow restrictors.

A 2-month-old female (3.4 kg, 50 cm) with Down syndrome and left-to-right shunting congenital heart defects underwent an unsuccessful transcatheter ductal closure, followed by bilateral implantation of manually modified microvascular plugs (MVP-9Q) from Medtronic (Minneapolis, MN, USA), used as pulmonary flow restrictors. Post-procedure, she developed febrile respiratory distress, leading to admission to the intensive care unit.

Duloxetine enhances PAX6 expression and suppresses innate immune responses in murine LPS-induced corneal inflammation.

Background-aim: PAX6 is a key regulator of eye development and epithelial homeostasis in the cornea. When deficient, chronic corneal inflammation, neovascularization and limbal stem cell deficiency can occur. Here we investigated the potential of duloxetine, a generic serotonin reuptake inhibitor that can upregulate PAX6 in vitro, for its in vivo activity in the context of corneal inflammation.

Climate change and children's respiratory health.

Climate change has significant consequences for children's respiratory health. Rising temperatures and extreme weather events increase children's exposure to allergens, mould, and air pollutants. Children are particularly vulnerable to these airborne particles due to their higher ventilation per unit of body weight, more frequent mouth breathing, and outdoor activities.

Supra-tentorial Ependymomas with ZFTA Fusion, YAP1 Fusion, and Astroblastomas, MN1-altered: Characteristic Imaging Features.

Purpose: Supratentorial (ST) ependymoma subgroups are defined by two different fusions with different prognoses. Astroblastomas, MN1-altered, have ependymal-like histopathologic features and represent a differential diagnosis in children. We hypothesized that ZFTA-fused ependymoma and YAP1-fused ependymoma on the one hand, and astroblastoma, MN1-altered, on the other hand, show different MRI characteristics.

Metabolomics Analysis of Rabbit Plasma after Ocular Exposure to Vapors of Sulfur Mustard.

Sulfur mustard (SM) is a highly potent alkylating vesicant agent and remains a relevant threat to both civilians and military personnel. The eyes are the most sensitive organ after airborne SM exposure, causing ocular injuries with no antidote or specific therapeutics available. In order to identify relevant biomarkers and to obtain a deeper understanding of the underlying biochemical events, we performed an untargeted metabolomics analysis using liquid chromatography coupled to high-resolution mass spectrometry of plasma samples from New Zealand white rabbits ocularly exposed to vapors of SM.

Pregnancy in Times of War: What Are the Fallouts? A Review.

Background: The beginning of the conflict in Ukraine has reminded Europeans of the many and diverse consequences of armed conflicts. Indeed, the ever more sophisticated conflicts have led to the diffusion of numerous chemicals whose consequences spread even after the end of the war. We present through this paper a review of the consequences of pregnancies from the major conflicts that took place since the end of World War II.

Precision treatment of beta-cell monogenic diabetes: a systematic review.

Background: Beta-cell monogenic forms of diabetes have strong support for precision medicine. We systematically analyzed evidence for precision treatments for GCK-related hyperglycemia, HNF1A-, HNF4A- and HNF1B-diabetes, and mitochondrial diabetes (MD) due to m.3243 A > G variant, 6q24-transient neonatal diabetes mellitus (TND) and SLC19A2-diabetes.

Interleukin (IL)-1/IL-6-Inhibitor-Associated Drug Reaction With Eosinophilia and Systemic Symptoms (DReSS) in Systemic Inflammatory Illnesses.

Background: After introducing IL-1/IL-6 inhibitors, some patients with Still and Still-like disease developed unusual, often fatal, pulmonary disease. This complication was associated with scoring as DReSS (drug reaction with eosinophilia and systemic symptoms) implicating these inhibitors, although DReSS can be difficult to recognize in the setting of systemic inflammatory disease.

Objective: To facilitate recognition of IL-1/IL-6 inhibitor-DReSS in systemic inflammatory illnesses (Still/Still-like) by looking at timing and reaction-associated features.

Full circumferential human tracheal replacement: a systematic review.

Full Circumferential Tracheal Replacement (FCTR) is a surgical challenge, indicated in rare cases of extensive tracheal resection, with no consensus on surgical technique or materials. A systematic review according to PRISMA guidelines was carried out from 2000 to 2022 to identify cases of FCTR, to compare surgical indications, the nature of the tracheal substitutes and their immunological characteristics, surgical replacement techniques and vascularization. Thirty-seven patients, including five children, underwent FCTR surgery using 4 different techniques: thyrotracheal complex allograft (n = 2), aorta (n = 12), autologous surgical reconstruction (n = 19), tissue-engineered decellularized trachea (n = 4).

Specific brain MRI features of constitutional mismatch repair deficiency syndrome in children with high-grade gliomas.

Background: Children with constitutional mismatch repair deficiency (CMMRD) syndrome have an increased risk of high-grade gliomas (HGG), and brain imaging abnormalities. This study analyzes brain imaging features in CMMRD syndrome children versus those with HGG without CMMRD.

Methods: Retrospective comparative analysis of brain imaging in 30 CMMRD children (20 boys, median age eight years, 22 with HGG), seven with Lynch syndrome (7 HGG), 39 with type 1 neurofibromatosis (NF1) (four with HGG) and 50 with HGG without MMR or NF1 pathogenic variant ("no-predisposition" patients).