Translational Preclinical PET Imaging and Metabolic Evaluation of a New Cannabinoid 2 Receptor (CBR) Radioligand, ()--(3-(2-(2-[F]Fluoroethoxy)ethyl)-4,5-dimethylthiazol-2(3)-ylidene)-2,2,3,3-tetramethylcyclopropane-1-carboxamide.

We have previously developed seven fluorinated analogues of A-836339 as new PET tracers for cannabinoid type 2 receptor (CBR) imaging, among which ()--(3-(2-(2-[F]fluoroethoxy)ethyl)-4,5-dimethylthiazol-2(3)-ylidene)-2,2,3,3-tetramethylcyclopropane-1-carboxamide ([F]FC0324) displayed high affinity and selectivity for CBR in healthy rats. In the present study, we have further evaluated the imaging and metabolic properties of [F]FC0324 in a rat model of human CBR overexpression in the brain (AAV-CB) and in non-human primates (NHPs). Autoradiography with AAV-CB rat brain sections exhibited a signal of [F]FC0324 8-fold higher in the ipsilateral region than in the contralateral region.

EULAR/PReS recommendations for the diagnosis and management of Still's disease, comprising systemic juvenile idiopathic arthritis and adult-onset Still's disease.

Unlabelled: Systemic juvenile idiopathic arthritis (sJIA) and adult-onset Still's disease (AOSD) are considered the same disease, but a common approach for diagnosis and management is still missing.

Methods: In May 2022, EULAR and PReS endorsed a proposal for a joint task force (TF) to develop recommendations for the diagnosis and management of sJIA and AOSD. The TF agreed during a first meeting to address four topics: similarity between sJIA and AOSD, diagnostic biomarkers, therapeutic targets and strategies and complications including macrophage activation syndrome (MAS).

Severe neurodevelopmental phenotype, diagnostic, and treatment challenges in patients with SECISBP2 deficiency.

Purpose: Defects in the gene encoding selenocysteine insertion sequence binding protein 2, SECISBP2, result in global impaired selenoprotein synthesis manifesting a complex syndrome with characteristic serum thyroid function tests due to impaired thyroid hormone metabolism. Knowledge about this multisystemic defect remains limited.

Methods: Genetic and laboratory investigations were performed in affected members from 6 families presenting with short stature and failure to thrive.

Standardized emergency protocols to improve the management of patients with suspected or confirmed inherited metabolic disorders (IMDs): An initiative of the French IMDs Healthcare Network for Rare Diseases.

Objectives: Patients with inherited metabolic disorders (IMDs) may require emergency hospital care to prevent life-threatening situations such as metabolic decompensation. To date, over one thousand different rare IMDs have been identified, which means that healthcare professionals (HCPs) initiating emergency treatment may not be familiar with these conditions. The objective of this initiative was to provide HCPs with practical guidance for the acute management of children and adults with IMDs who need emergency care, regardless of the underlying reason.

Description, clinical impact and early outcome of S. maltophilia respiratory tract infections after lung transplantation, A retrospective observational study.

Background And Research Question: S. maltophilia infections are associated with significant morbidity and mortality. Little is known regarding its presentation, management, and outcome in lung transplant recipients.

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.