Using the Key Characteristics Framework to Unlock the Mysteries of Aryl Hydrocarbon Receptor-Mediated Effects on the Immune System.

Initially discovered for its role mediating the deleterious effects of environmental contaminants, the aryl hydrocarbon receptor (AHR) is now known to be a crucial regulator of the immune system. The expanding list of AHR ligands includes synthetic and naturally derived molecules spanning pollutants, phytochemicals, pharmaceuticals, and substances derived from amino acids and microorganisms. The consequences of engaging AHR vary, depending on factors such as the AHR ligand, cell type, immune challenge, developmental state, dose, and timing of exposure relative to the immune stimulus.

Alternative splicing generates isoform diversity in .

Although the gene has a long-standing association with cancer, its mechanisms of action remain incompletely understood, acting both as a tumour suppressor in neuroendocrine tumours and as an oncogene in leukaemia. The best-characterised isoform of the encoded protein, MENIN, is the 610-amino acid MENIN isoform 2. We hypothesise that some of the complexity of biology can be attributed to a currently unappreciated contribution of different MENIN isoforms.

Weight maintenance on cost-effective antiobesity medications after 1 year of GLP-1 receptor agonist therapy: a real-world study.

Objective: The high cost of novel glucagon-like peptide-1 receptor agonist (GLP-1 RA) class agents often limits access and creates barriers to care. This real-world study evaluated the efficacy of older-generation generic antiobesity medications (AOMs) for weight maintenance after 1 year of GLP-1 RA therapy in patients who had achieved successful weight loss.

Methods: We prospectively followed patients (N = 105) who had completed 12 months of therapy and were part of a "medical weight loss bundle," which included 12 months of GLP-1 RA therapy followed by 6 months of transition care.

Compensatory mechanisms that maintain androgen production in mice lacking key androgen biosynthetic enzymes.

Testosterone and dihydrotestosterone (DHT) are essential for male development and fertility. In the canonical androgen production pathway, testosterone is produced in the testis by HSD17B3; however, adult male Hsd17b3 knockout (KO) mice continue to produce androgens and are fertile, indicating compensatory mechanisms exist. A second, alternate pathway produces DHT from precursors other than testosterone via 5α-reductase (SRD5A) activity.

Self-reported drink driving, enforcement, crashes, and crash reporting: A 6-country comparison.

Objective: The objective of this study was to compare drink driving and related road safety issues in 2 urban areas of 6 countries and develop an equation for estimating the rate of crash underreporting to the police in urban areas of countries that lack this information.

Methods: This study is a secondary analysis of 1 to 2 waves of surveys in pairs of matched medium-sized cities in Belgium, Brazil, China, Mexico, South Africa, and Ohio, United States; the surveys supported evaluation of local alcohol harm reduction efforts. Data were from 2017 to 2019 except 2023 for Mexico.

A reassessment of spinal cord pathology in severe infantile spinal muscular atrophy: Reassessment of spinal cord pathology.

Aims: Spinal muscular atrophy (SMA) is a life-limiting paediatric motor neuron disease characterised by lower motor neuron loss, skeletal muscle atrophy and respiratory failure, if untreated. Revolutionary treatments now extend patient survival. However, a limited understanding of the foundational neuropathology challenges the evaluation of therapeutic success.

Blending space and time to talk about cancer in extended reality.

We introduce a proof-of-concept extended reality (XR) environment for discussing cancer, presenting genomic information from multiple tumour sites in the context of 3D tumour models generated from CT scans. This tool enhances multidisciplinary discussions. Clinicians and cancer researchers explored its use in oncology, sharing perspectives on XR's potential for use in molecular tumour boards, clinician-patient communication, and education.

DMT1 knockout abolishes ferroptosis induced mitochondrial dysfunction in C. elegans amyloid β proteotoxicity.

Iron is critical for neuronal activity and metabolism, and iron dysregulation alters these functions in age-related neurodegenerative disorders, such as Alzheimer's disease (AD). AD is a chronic neurodegenerative disease characterized by progressive neuronal dysfunction, memory loss and decreased cognitive function. AD patients exhibit elevated iron levels in the brain compared to age-matched non-AD individuals.

Hangman's Fractures: A Review of Current Concepts in Evaluation and Management.

Study Design: Review article.

Objective: To provide a comprehensive review and update on the evaluation and management of Hangman's fractures.

Summary Of Background Data: Hangman's fractures are the second most common fracture of the C2 vertebrae, and the prevalence is increasing with our aging population.

Therapeutic CRISPR epigenome editing of inflammatory receptors in the intervertebral disc.

Low back pain (LBP) ranks among the leading causes of disability worldwide and generates a tremendous socioeconomic cost. Disc degeneration, a leading contributor to LBP, can be characterized by the breakdown of the extracellular matrix of the intervertebral disc (IVD), disc height loss, and inflammation. The inflammatory cytokine tumor necrosis factor α (TNF-α) has multiple signaling pathways, including proinflammatory signaling through tumor necrosis factor receptor 1 superfamily, member 1a (TNFR1 or TNFRSF1A), and has been implicated as a primary mediator of disc degeneration.

The effect of lumbar medial branch radiofrequency neurotomy on cobb angle progression in individuals with adult scoliosis compared to natural history: A cross-sectional study.

Background: Lumbar radiofrequency neurotomy (LRFN) effectively alleviates zygapophyseal joint-mediated pain by coagulating medial branch nerves to disrupt nociceptive signaling pathways. The concomitant denervation of multifidus fibers has led to concern that LRFN may increase segmental instability and accelerate degenerative changes in patients with certain pre-existing spinal pathologies. There is a paucity of literature evaluating whether LRFN increases the progression of spinal curvature in patients with adult scoliosis.

Supporting healthcare professionals to reduce weight stigma.

Background: Reducing weight stigma in healthcare is critical to supporting and improving the health of people living with overweight or obesity and decreasing the risk of adverse patient outcomes. We were invited as stigma researchers to participate in an online workshop alongside community members, healthcare professionals and policymakers to codesign guidance for reducing weight stigma in healthcare. This workshop prompted us to reflect on why and how weight stigma should be addressed in healthcare, and to provide recommendations for healthcare professionals and policymakers to reduce weight stigma in healthcare.

Silk-Derived Protein-4 Versus Vehicle Control in Treating Patients With Moderate to Severe Dry Eye Disease: A Randomized Clinical Trial.

Purpose: In this study the safety and efficacy of silk-derived protein 4 (SDP-4), also known as amlisimod, eye drops against a vehicle control formulation in patients with moderate to severe dry eye disease (DED) was assessed. SDP-4 is a novel, naturally derived, anti-inflammatory wetting agent that enhances coating on the ocular surface.

Design: Exploratory Phase 2, 12- and 8-week, serial cohort, multicenter, double-masked, randomized, vehicle-controlled study.

DMT1 knockout abolishes ferroptosis induced mitochondrial dysfunction in amyloid β proteotoxicity.

Iron is critical for neuronal activity and metabolism, and iron dysregulation alters these functions in age-related neurodegenerative disorders, such as Alzheimer's disease (AD). AD is a chronic neurodegenerative disease characterized by progressive neuronal dysfunction, memory loss and decreased cognitive function. AD patients exhibit elevated iron levels in the brain compared to age-matched non-AD individuals.

A Falls Prevention Program for People After Stroke in Guyana: An International Collaboration.

Objective: The objective was to describe the social, environmental, and cultural adaptations to an existing falls program and assess acceptability and preliminary effectiveness of the program in reducing fear, reducing falls, and improving function among individuals poststroke in Guyana.

Methods: A quasi-experimental pilot study with a pretest/posttest in-group design was developed through a collaboration of researchers in Guyana and the US. Participants took part in the falls prevention program for 8 weeks.

Protocol for the Development and Initial Validation of the COG-IMPACT Tool: A Purpose-Built Unmet Needs Assessment for Cancer-Related Cognitive Impairment.

(1) : A significant proportion of cancer survivors report experiencing a cognitive 'fog' that affects their ability to think coherently and quickly, and reason with clarity. This has been referred to as cancer-related cognitive impairment (CRCI). CRCI has extensive impacts on the daily lives of people living with or beyond cancer, including occupational, social, and psychological functioning.

Transthyretin amyloidosis in spinal canal stenosis: A systematic review.

We systematically review literature regarding the contribution of transthyretin amyloidosis to spinal stenosis. Amyloidosis is a protein misfolding condition that causes systemic deposition of amyloid and commonly leads to heart failure and nephropathy. A growing body of literature suggests that amyloid deposits within the ligamentum flavum are frequently associated with spinal stenosis with subsequent myelopathy.

Factors Related to Clinical Performance in Spine Surgery Fellowship: Can We Predict Success.

Introduction: The factors most important in the spine fellowship match may not ultimately correlate with quality of performance during fellowship. This study examined the spine fellow applicant metrics correlated with high application rank compared with the metrics associated with the strongest clinical performance during fellowship.

Methods: Spine fellow applications at three academic institutions were retrieved from the San Francisco Match database (first available to 2021) and deidentified for application review.

Binary and quaternary mixtures of perfluoroalkyl substances (PFAS) differentially affect the immune response to influenza A virus infection.

Per- and polyfluoroalkyl substances (PFAS) are anthropogenic organofluorine compounds that persist indefinitely in the environment and bioaccumulate throughout all trophic levels. Biomonitoring efforts have detected multiple PFAS in the serum of most people. Immune suppression has been among the most consistent effects of exposure to PFAS.

Timing influences the impact of aryl hydrocarbon receptor activation on the humoral immune response to respiratory viral infection.

Humoral responses to respiratory viruses, such as influenza viruses, develop over time and are central to protection from repeated infection with the same or similar viruses. Epidemiological and experimental studies have linked exposures to environmental contaminants that bind the aryl hydrocarbon receptor (AHR) with modulated antibody responses to pathogenic microorganisms and common vaccinations. Other studies have prompted investigation into the potential therapeutic applications of compounds that activate AHR.