Gut microbiota and microbial metabolites are associated with body composition in 5-year-old children: A cross-sectional study in the Gen3G cohort.

Objective: To examine gut microbiota diversity, composition and metabolites in relation to overall mass (OM), fat mass (FM) and lean soft tissue mass (LSTM) measured by dual x-ray absorptiometry (DXA) in 5-year-old children.

Methods: Mothers of the Gen3G cohort were enrolled prenatally in 2010-2013 in Quebec, Canada; 153 children from the cohort had data on gut microbiota and DXA scans at 5-6.4 years of age, and 140 also had plasma metabolite data.

Seizures associated with dural arteriovenous fistulas: A systematic review of cases.

Objective: Dural arteriovenous fistulas (DAVFs) are an unusual cause of seizures. In this systematic review, we aim to describe the clinical features, paraclinical findings, management, and prognosis of cases of DAVF-related seizures, raising awareness for a potentially treatable cause of epilepsy.

Methods: This review was registered on PROSPERO (CRD42024529316).

Pain experience of children with Christianson syndrome.

Children with Christianson syndrome (CS), an X-linked neurodevelopmental disorder caused by loss-of-function mutations in the alkali cation/proton exchanger SLC9A6/NHE6, display severe cognitive impairments, mutism, and sensory abnormalities such as hyposensitivity to pain. However, it is unclear whether these children display other sensory abnormalities and whether their pain hyposensitivity is the result of an elevated pain threshold or a complete insensitivity to pain. To better characterize the sensory abnormalities in this disorder, we used a combination of a mouse model of CS and pain questionnaires directed at nonverbal patients with CS.

Oral Sodium Loading Test Is More Sensitive Than Seated Saline Infusion Test to Confirm Overt Primary Aldosteronism.

Context: Primary aldosteronism (PA), a frequent but underdiagnosed cause of hypertension, is associated with a significant burden of cardiovascular and renal complications. Studies have reported divergent results regarding the diagnostic performance of seated saline infusion test (SSIT) and oral sodium loading test (OSLT), 2 confirmatory tests recommended by the Endocrine Society Clinical Practice Guidelines. To our knowledge, no study directly compared the results of SSIT and OSLT to diagnose overt PA.

Cardiac Conduction Delay for Sodium Channel Antagonist Antiseizure Medications: An Analysis of the Canadian Longitudinal Study on Aging.

Background And Objectives: People with epilepsy are at risk of cardiac arrhythmias. Whether this association results from epilepsy, antiseizure medications (ASMs) such as sodium channel blockers (NABs), or other factors has not been systematically assessed. The aims of this study were to quantify the odds of cardiac conduction delays (CCDs) on electrocardiogram in older people with active epilepsy using vs not using NABs, to determine the prevalence of CCDs by NABs, and to examine the association of demographic and clinical factors with CCDs.

What Is the Role of Fecal Microbiota Transplantation in Immunotherapy Trials? Current Perspectives and Future Directions.

Immune checkpoint inhibitors (ICIs) are rapidly transforming the treatment landscape of genitourinary and other immunogenic malignancies. Despite these advances, biomarkers for the prediction of ICI response remain to be established. The gut microbiome has been identified as a modulator of immune regulation and a potential regulator of response to ICIs.

Under-recognised neurocognitive deficits in adults and adolescents with tuberous sclerosis complex.

Background: Tuberous sclerosis complex (TSC) is a genetic disease characterised by the growth of benign tumours. The Tuberous sclerosis Associated Neuropsychiatric Disorders (TAND) Checklist is used to identify patient-reported neurocognitive deficits. Patients may, however, under-recognise mild cognitive impairment.

Distinct peripheral pro-inflammatory profile associated with tuberous sclerosis complex and epilepsy.

Objective: Tuberous sclerosis complex (TSC) is a monogenetic disorder associated with sustained mechanistic target of rapamycin (mTOR) activation, leading to heterogeneous clinical manifestations. Epilepsy and renal angiomyolipoma are the most important causes of morbidity in adult people with TSC (pwTSC). mTOR is a key player in inflammation, which in turn could influence TSC-related clinical manifestations.

Canadian Consensus Recommendations for Predictive Biomarker Testing in Gastric and Gastroesophageal Junction Adenocarcinoma.

Gastric cancer is common globally and has a generally poor prognosis with a low 5-year survival rate. Targeted therapies and immunotherapies have improved the treatment landscape, providing more options for efficacious treatment. The use of these therapies requires predictive biomarker testing to identify patients who can benefit from their use.

Improving Gout Care in a Canadian Academic Medical Center Through a Multidisciplinary, Nurse-Led Protocol.

Objective: Following Health Canada's knowledge translation framework, we report the results of a clinical audit from 2012 to 2015 followed by a multidisciplinary, nurse-led gout care protocol with a treat-to-target (T2T) strategy implemented in April 2018.

Methods: A clinical audit with chart reviewing was completed for adults with gout and urate-lowering therapy (ULT) indication at the Centre Hospitalier Universitaire de Sherbrooke. A nurse-led treatment algorithm using allopurinol was then developed.

Evaluating the Efficacy of Immunotherapy in Fragile Hospitalized Patients.

Background: Immunotherapy is the cornerstone of treatment for many cancers. The effectiveness of immunotherapy in hospitalized patients is unknown due to the exclusion of this fragile population from clinical trials. This study evaluates the efficacy of immunotherapy in fragile hospitalized patients.

Low physical fitness indicates future injury, mental health, menstrual cycle disruptions, and burnout in female emergency service personnel and healthcare providers.

Musculoskeletal injury (MSKi), depression, anxiety, and burnout place a considerable burden on emergency services personnel and healthcare providers (HCP). Physical fitness is related to both mental and physical health in these populations, but females in these are hugely underrepresented in this literature. As female representation in first-responder and HCP roles increases, the need for female-specific research is needed.

Alternative Strategies for Delivering Immunotherapeutics Targeting the PD-1/PD-L1 Immune Checkpoint in Cancer.

The programmed death-1/programmed death-ligand 1 (PD-1/PD-L1) immune checkpoint constitutes an inhibitory pathway best known for its regulation of cluster of differentiation 8 (CD8) T cell-mediated immune responses. Engagement of PD-L1 with PD-1 expressed on CD8 T cells activates downstream signaling pathways that culminate in T cell exhaustion and/or apoptosis. Physiologically, these immunosuppressive effects exist to prevent autoimmunity, but cancer cells exploit this pathway by overexpressing PD-L1 to facilitate immune escape.

Associations of gut microbiota features and circulating metabolites with systemic inflammation in children.

Objective: Gut microbes and microbe-dependent metabolites (eg, tryptophan-kynurenine-serotonin pathway metabolites) have been linked to systemic inflammation, but the microbiota-metabolite-inflammation axis remains uncharacterised in children. Here we investigated whether gut microbiota features and circulating metabolites (both microbe-dependent and non-microbe-dependent metabolites) associated with circulating inflammation markers in children.

Methods: We studied children from the prospective Gen3G birth cohort who had data on untargeted plasma metabolome (n=321 children; Metabolon platform), gut microbiota (n=147; 16S rRNA sequencing), and inflammation markers (plasminogen activator inhibitor-1 (PAI-1), monocyte chemoattractant protein-1, and tumour necrosis factor-α) measured at 5-7 years.

In vivo dissection of the mouse tyrosine catabolic pathway with CRISPR-Cas9 identifies modifier genes affecting hereditary tyrosinemia type 1.

Hereditary tyrosinemia type 1 is an autosomal recessive disorder caused by mutations (pathogenic variants) in fumarylacetoacetate hydrolase, an enzyme involved in tyrosine degradation. Its loss results in the accumulation of toxic metabolites that mainly affect the liver and kidneys and can lead to severe liver disease and liver cancer. Tyrosinemia type 1 has a global prevalence of approximately 1 in 100,000 births but can reach up to 1 in 1,500 births in some regions of Québec, Canada.

Newborn adiposity is associated with cord blood DNA methylation at IGF1R and KLF7.

Objective: This study aimed to identify whether cord blood DNA methylation at specific loci is associated with neonatal adiposity, a key risk factor for childhood obesity.

Methods: An epigenome-wide association study was conducted using the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) Study as a discovery sample. Linear regression models adjusted for maternal and offspring covariates and cell counts were used to analyze associations between neonatal adiposity as measured by sum of three skinfold thicknesses and cord blood DNA methylation.

Oxidative stress-induced YAP1 expression is regulated by NCE102, CDA2, and BCS1.

Maintaining cellular homeostasis in the face of stress conditions is vital for the overall well-being of an organism. Reactive oxygen species (ROS) are among the most potent cellular stressors and can disrupt the internal redox balance, giving rise to oxidative stress. Elevated levels of ROS can severely affect biomolecules and have been associated with a range of pathophysiological conditions.