Brain malformations and seizures by impaired chaperonin function of TRiC.

Malformations of the brain are common and vary in severity, from negligible to potentially fatal. Their causes have not been fully elucidated. Here, we report pathogenic variants in the core protein-folding machinery TRiC/CCT in individuals with brain malformations, intellectual disability, and seizures.

TLR2 Activation as a Marker of Severe COVID-19 and a Potential Therapeutic Target.

SARS-CoV-2-induced COVID-19 has been a serious public health problem, resulting in millions of lives lost over the previous three years. Although the direct infection caused by virus invasion is important for the pathobiology of COVID-19, the hyperinflammatory response and tissue injury are major contributors in critically ill patients. As a host sensor, toll-like receptor 2 (TLR2) recognizes multiple pathogen-associated molecular patterns (PAMPs) or damage-associated molecular patterns (DAMPs), producing various inflammatory cytokines and inflammatory cell death signals, which are central to the inflammatory pathology observed in COVID-19.

Deprescribing Antidepressants in Children and Adolescents: A Systematic Review of Discontinuation Approaches, Cross-Titration, and Withdrawal Symptoms.

Antidepressant medications, including selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs), are commonly used to treat depressive, anxiety, and obsessive-compulsive disorders in youth. Yet, data on discontinuing these medications, withdrawal symptoms, and strategies to switch between them are limited. We searched PubMed and ClinicalTrials.

How teaching surgeons communicate: An analysis of intraoperative discourse among male and female surgeons.

Background: Our objective was to compare the use of agentic ("I") and communal ("we") spoken intraoperative discourse between male and female attending and resident surgeons.

Methods: We analyzed transcripts involving attending and resident surgeons from 5 specialties at a single Midwestern academic teaching hospital. We adapted and expanded Grebelsky-Lichtman's codes, assessed rater agreement, and systematically coded transcripts for agentic and communal terms.

Proteomics Analysis on the Effects of Oxidative Stress and Antioxidants on Proteins Involved in Sterol Transport and Metabolism in Human Telomerase Transcriptase-Overexpressing-Retinal Pigment Epithelium Cells.

Age-related macular degeneration (AMD) is the most prevalent ocular disease in the elderly, resulting in blindness. Oxidative stress plays a role in retinal pigment epithelium (RPE) pathology observed in AMD. Tocopherols are potent antioxidants that prevent cellular oxidative damage and have been shown to upregulate the expression of cellular antioxidant proteins.

Survodutide for the Treatment of Obesity: Rationale and Design of the SYNCHRONIZE Cardiovascular Outcomes Trial.

Dual agonism of glucagon and glucagon-like peptide-1 (GLP-1) receptors may be more effective than GLP-1 receptor agonism alone in reducing body weight, but the cardiovascular (CV) effects are unknown. The authors describe the rationale and design of SYNCHRONIZE-CVOT, a phase 3, randomized, double-blind, parallel-group, event-driven, CV safety study of survodutide, a dual glucagon and GLP-1 receptor agonist, administered subcutaneously once weekly compared with placebo in adults with a body mass index ≥27 kg/m and established CV disease or chronic kidney disease, and/or at least 2 weight-related complications or risk factors for CV disease. The primary endpoint of SYNCHRONIZE-CVOT is time to first occurrence of the composite adjudicated endpoint of 5-point major adverse CV events.

Post-operative care for patients following surgical treatment of lymphedema.

Surgical treatments are promising for the treatment of lymphedema. It is important for patients, healthcare providers, and lymphedema community to understand that surgical treatments currently are not a cure for lymphedema but have provided promising options for patients. Post-operative care for patients following surgical treatment of lymphedema is vital to optimize and sustain patient outcomes.

Associations of Neighborhood Food Retail Environments with Weight Status in a Regional Pediatric Health System.

There have been mixed findings on the relationships between childhood obesity and macroscale retail food environments. The current study investigates associations of the neighborhood retail food environment with changes in children's weight status over 6 years in the Kansas City Metropolitan area. Anthropometrics and home addresses were collected during routine well-child visits in a large pediatric hospital ( = 4493; >75% were Black or Latinx children).

Outcomes with revascularisation versus conservative management of participants with 3-vessel coronary artery disease in the ISCHEMIA trial.

Background: Whether revascularisation (REV) improves outcomes in patients with three-vessel coronary artery disease (3V-CAD) is uncertain.

Aims: Our objective was to evaluate outcomes with REV (percutaneous coronary intervention [PCI] or coronary artery bypass graft surgery [CABG]) versus medical therapy in patients with 3V-CAD.

Methods: ISCHEMIA participants with 3V-CAD on coronary computed tomography angiography without prior CABG were included.

Management of Visually Significant Vitreous Opacities.

Visual floaters can significantly affect quality of vision. Although these opacities are visible on ophthalmoscopy, objectively measuring severity has been difficult. The standard approach has been to monitor individuals for complications rather than treating the floaters.

Cardiovascular, autonomic symptoms and quality of life in children with hypermobile Ehlers-Danlos syndrome.

Objectives: Hypermobile Ehlers-Danlos syndrome is a connective tissue disorder characterized by joint hypermobility and other systemic manifestations. Cardiovascular, autonomic symptoms and dysautonomia are frequently reported in adults with hypermobile Ehlers-Danlos syndrome and have been shown to have a negative impact on quality of life. However, there is scant literature on autonomic symptoms in pediatric patients with hypermobile Ehlers-Danlos syndrome.