Systems immunology integrates the complex endotypes of recessive dystrophic epidermolysis bullosa.

Endotypes are characterized by the immunological, inflammatory, metabolic, and remodelling pathways that explain the mechanisms underlying the clinical presentation (phenotype) of a disease. Recessive dystrophic epidermolysis bullosa (RDEB) is a severe blistering disease caused by COL7A1 pathogenic variants. Although underscored by animal studies, the endotypes of human RDEB are poorly understood.

Robot-assisted laparoscopic continent cutaneous urinary diversion in adults: A single-centre study.

Objectives: To show that robot-assisted laparoscopic cutaneous continent urinary diversion (RALCCUD) is feasible and safe; however, data on clinical outcomes in adults are lacking.

Materials And Methods: We conducted a retrospective study of all adults who underwent RALCCUD between 2017 and 2022 at a single tertiary reference centre.Patient characteristics, clinical information and perioperative outcomes were recorded.

Exploring winter diet, gut microbiota and parasitism in caribou using multi-marker metabarcoding of fecal DNA.

In conservation strategies, getting precise and repeatable information on the species' diet and health without relying on invasive or laborious methods is challenging. Here, we developed an efficient and non-invasive workflow for the sequencing and analysis of four taxonomic markers from fecal DNA to characterize the gut microbiota, parasites, and plants and lichens composing the winter diet of caribou (Rangifer tarandus), Canada's most iconic endangered species. Sequencing of the 18S rRNA gene of eukaryotes from seven locations in Manitoba and Saskatchewan, Canada, allowed for the detection of five genera of parasites in caribou feces (including Nematodirella and Parelaphostrongylus) with variable frequency of occurrence depending on sampling location and sex.

Direct medical costs of cardiovascular diseases: Do cost components vary according to sex and age?

Background: The aim was to estimate direct medical costs of men and women patients by age group related to cardiovascular diseases (coronary heart disease, strokes) in the province of Quebec, Canada from the economic perspective of the healthcare public system, encompassing five cost components: physician fees, hospitalization (hospital stay, intensive care stay), emergency visits and medication costs.

Methods: This matched case-control study involved secondary data from a longitudinal cohort study (1997-2018) of 4584 white-collar workers. Participants were followed for a four-year period.

The evolution of mesenchymal stem cell-derived neural progenitor therapy for Multiple Sclerosis: from concept to clinic.

This review delves into the generation and therapeutic applications of mesenchymal stem cell-derived neural progenitors (MSC-NPs) in Multiple Sclerosis (MS), a chronic autoimmune disease characterized by demyelination, neuroinflammation, and progressive neurological dysfunction. Most current treatment paradigms primarily aimed at regulating the immune response show little success against the neurodegenerative aspect of MS. This calls for new therapies that would play a role in neurodegeneration and functional recovery of the central nervous system (CNS).

Performance of the Social Responsiveness Scale-2 for the Assessment of Autistic Behaviors in a Sample of Canadian Preschool-Aged Children.

Behavioral traits of autism spectrum disorder (ASD) typically present in early childhood, underscoring the importance of screening tools for the early identification of ASD. The current study compared scores on the Social Responsiveness Scale-Second Edition (SRS-2) Preschool Form between the US standardization sample (n = 247) and a Canadian cohort of preschool-aged children (n = 595) recruited from the Maternal-Infant Research on Environmental Chemicals (MIREC) study. In the MIREC sample, we examined whether ASD-like traits are correlated with sociodemographic characteristics and child intellectual abilities, and how maternal ratings of social skills assessed by the SRS-2 are associated with maternal ratings of general problem behaviors.

Updated review on contaminant communication experiences in the circumpolar Arctic.

Arctic populations are amongst the highest exposed populations to long-range transported contaminants globally, with the main exposure pathway being through the diet. Dietary advice is an important immediate means to address potential exposure and help minimize adverse health effects. The objective of this work is to enable easier access to dietary advice and communication guidance on contaminants with a focus on the Arctic.

Biomedical Device Surface Treatment by Laser-Driven Hydroxyapatite Penetration-Synthesis Technique for Gapless PEEK-to-Bone Integration.

Polyetheretherketone (PEEK), a bioinert polymer known for its mechanical properties similar to bone, is capable of averting stress shielding. Due to these attributes, it finds applications in diverse fields like orthopedics, encompassing cervical disc replacement for the neck and spine, along with dentistry and plastic surgery. However, due to insufficient bonding with bone, various methods such as hydroxyapatite (HA) coating on the surface are attempted.

Reconstruction of remodeling units reveals positive effects after 2 and 12 months of romosozumab treatment.

Romosozumab treatment results in a transient early increase in bone formation and sustained decrease in bone resorption. Histomorphometric analyses revealed that the primary bone-forming effect of romosozumab is a transient early stimulation of modeling-based bone formation on cancellous and endocortical surfaces. Furthermore, preclinical studies have demonstrated that romosozumab may affect changes in the remodeling unit, resulting in positive bone balance.

Postfracture survival in a population-based study of adults aged ≥66 yr: a call to action at hospital discharge.

Postfracture survival rates provide prognostic information but are rarely reported along with other mortality outcomes in adults aged ≥50 yr. The timing of survival change following a fracture also needs to be further elucidated. This population-based, matched-cohort, retrospective database study examined 98 474 patients (73% women) aged ≥66 yr with an index fracture occurring at an osteoporotic site (hip, clinical vertebral, proximal non-hip non-vertebral [pNHNV], and distal non-hip non-vertebral [dNHNV]) from 2011 to 2015, who were matched (1:1) to nonfracture individuals based on sex, age, and comorbidities.

Multiple Sclerosis Research Evolves: A Closer Look at Deep Gray Matter, Sexual Function Rehabilitation, and T Regulatory Cells.

Multiple sclerosis (MS) is a chronic autoimmune condition that leads to the loss of myelin and, subsequently, neuronal damage in the central nervous system (CNS) [...

Gene therapy for Duchenne muscular dystrophy: an update on the latest clinical developments.

Introduction: Duchenne muscular dystrophy (DMD) is one of the most severe and devastating neuromuscular hereditary diseases with a male newborn incidence of 20 000 cases each year. The disease caused by mutations (exon deletions, nonsense mutations, intra-exonic insertions or deletions, exon duplications, splice site defects, and deep intronic mutations) in the DMD gene, progressively leads to muscle wasting and loss of ambulation. This situation is painful for both patients and their families, calling for an emergent need for effective treatments.

Where do we look for the next breakthrough in sleep research?

The wakefulness-sleep cycle sets the pace of our life. Sleep research examines the transition between wakefulness and sleep, its hormonal regulation, and its pathological disruption. Understanding sleep mechanisms would improve quality-of-life well beyond sleep itself.

The Synergistic Potential of Combining PD-1/PD-L1 Immune Checkpoint Inhibitors with NOD2 Agonists in Alzheimer's Disease Treatment.

Our research over the past decade has compellingly demonstrated the potential of Nucleotide-binding oligomerization domain-containing protein 2 (NOD2) receptor agonists in Alzheimer's disease (AD) treatment. These agonists facilitate the conversation of pro-inflammatory monocytes into patrolling monocytes, leading to the efficient clearance of amyloid-β (Aβ) in the AD-affected cerebrovascular system. This approach surpasses the efficacy of targeting Aβ formation, marking a significant shift in therapeutic strategies.

Aminosteroid RM-581 Decreases Cell Proliferation of All Breast Cancer Molecular Subtypes, Alone and in Combination with Breast Cancer Treatments.

Breast cancer (BC) is a heterogenous disease classified into four molecular subtypes (Luminal A, Luminal B, HER2 and triple-negative (TNBC)) depending on the expression of the estrogen receptor (ER), the progesterone receptor (PR) and the human epidermal receptor 2 (HER2). The development of effective treatments for BC, especially TNBC, remains a challenge. Aminosteroid derivative RM-581 has previously shown an antiproliferative effect in multiple cancers in vitro and in vivo.

Prime editing strategies to mediate exon skipping in gene.

Duchenne muscular dystrophy is a rare and lethal hereditary disease responsible for progressive muscle wasting due to mutations in the gene. We used the CRISPR-Cas9 Prime editing technology to develop different strategies to correct frameshift mutations in gene carrying the deletion of exon 52 or exons 45 to 52. With optimized epegRNAs, we were able to induce the specific substitution of the GT nucleotides of the splice donor site of exon 53 in up to 32% of HEK293T cells and 28% of patient myoblasts.

Evaluation of electroretinography (ERG) parameters as a biomarker for ADHD.

Background: The retina is recognized as an accessible part of the brain due to their common embryonic origin. The electroretinogram (ERG) has proven to be a valuable tool for detecting schizophrenia and bipolarity. We therefore investigated its ability to detect ADHD.

Role of Secreted Frizzled-Related Protein 1 in Early Breast Carcinogenesis and Breast Cancer Aggressiveness.

A human transcriptome array on ERα-positive breast cancer continuum of risk identified () as decreased during breast cancer progression. In addition, SFRP1 was inversely associated with breast tissue age-related lobular involution, and differentially regulated in women with regard to their parity status and the presence of microcalcifications. The causal role of in breast carcinogenesis remains, nevertheless, not well understood.

Prenatal and childhood chlordecone exposure, cognitive abilities and problem behaviors in 7-year-old children: the TIMOUN mother-child cohort in Guadeloupe.

Background: Chlordecone is a highly persistent organochlorine insecticide that was intensively used in banana fields in the French West Indies, resulting in a widespread contamination. Neurotoxicity of acute exposures in adults is well recognized, and empirical data suggests that prenatal exposure affects visual and fine motor developments during infancy and childhood, with greater susceptibility in boys.

Objective: To assess the associations between pre- and postnatal exposures to chlordecone and cognitive and behavioral functions in school-aged children from Guadeloupe.

PARP1 associates with R-loops to promote their resolution and genome stability.

PARP1 is a DNA-dependent ADP-Ribose transferase with ADP-ribosylation activity that is triggered by DNA breaks and non-B DNA structures to mediate their resolution. PARP1 was also recently identified as a component of the R-loop-associated protein-protein interaction network, suggesting a potential role for PARP1 in resolving this structure. R-loops are three-stranded nucleic acid structures that consist of a RNA-DNA hybrid and a displaced non-template DNA strand.

RNF213 Loss-of-Function Promotes Angiogenesis of Cerebral Microvascular Endothelial Cells in a Cellular State Dependent Manner.

Enhanced and aberrant angiogenesis is one of the main features of Moyamoya disease (MMD) pathogenesis. The ring finger protein 213 (RNF213) and the variant p.R4810K have been linked with higher risks of MMD and intracranial arterial occlusion development in east Asian populations.