CNTN4 modulates neural elongation through interplay with APP.

The neuronal cell adhesion molecule contactin-4 (CNTN4) is genetically associated with autism spectrum disorder (ASD) and other psychiatric disorders. Cntn4-deficient mouse models have previously shown that CNTN4 plays important roles in axon guidance and synaptic plasticity in the hippocampus. However, the pathogenesis and functional role of CNTN4 in the cortex has not yet been investigated. Our study found a reduction in cortical thickness in the motor cortex of Cntn4 -/- mice, but cortical cell migration and differentiation were unaffected. Significant morphological changes were observed in neurons in the M1 region of the motor cortex, indicating that CNTN4 is also involved in the morphology and spine density of neurons in the motor cortex. Furthermore, mass spectrometry analysis identified an interaction partner for CNTN4, confirming an interaction between CNTN4 and amyloid-precursor protein (APP). Knockout human cells for CNTN4 and/or APP revealed a relationship between CNTN4 and APP. This study demonstrates that CNTN4 contributes to cortical development and that binding and interplay with APP controls neural elongation. This is an important finding for understanding the physiological function of APP, a key protein for Alzheimer's disease. The binding between CNTN4 and APP, which is involved in neurodevelopment, is essential for healthy nerve outgrowth.

Type 1 diabetes mellitus disease burden in high health expenditure countries between 1990 and 2019.

OBJECTIVE: This observational study assesses trends in type 1 diabetes mellitus (T1DM) disease burden across the 19 countries of the European Union (EU) 15+ between 1990 and 2019. METHODS: The Global Burden of Disease Study database was used to gather T1DM age-standardised incidence (ASIR), prevalence (ASPR), mortality (ASMR), and disability-adjusted life-year (DALY) rates per 100,000 for each EU15+ country (1990 - 2019). Joinpoint regression analysis was used to describe the trends. RESULTS: From 1990 to 2019, T1DM ASIRs and ASPRs increased globally except for females in Finland (-2.9% and -9.4%), the largest increase in ASPR for males and females was observed in France (+144.4% and +137.5% respectively). All had reductions in ASMRs for males and females, with the largest observed in Spain (-56.7% and -79.0% respectively). Trends in DALYs were variable across countries, with increases in DALYs noted in 14/19 for males, and 9/19 for females. Denmark, Finland, Norway, Netherlands, and Sweden had a reduction in DALYs for both males and females. CONCLUSIONS: Mortality from T1DM is reducing across EU15+ countries, despite concomitant increases in incidence and prevalence rates. Trends in DALYs are variable across countries, reflecting differential trends in the disease burden across countries with similarly high health expenditure.

Colchicine for symptomatic coronary artery disease after percutaneous coronary intervention.

BACKGROUND: Percutaneous coronary intervention (PCI), the preferred coronary reperfusion strategy, induces endothelial trauma which may mount an inflammatory response. This has been shown to increase the likelihood of further major adverse cardiovascular events (MACE). Colchicine, a cheap and widely used anti-inflammatory has shown promise in improving cardiovascular outcomes. We aimed to perform a systematic review and meta-analysis to study the effects of colchicine in patients with symptomatic coronary artery disease (CAD) who have undergone PCI. METHOD: We systematically reviewed and meta-analysed 7 randomised controlled trials including a total of 6660 patients (colchicine group: 3347, control group: 3313; mean age=60.9±10). Six studies included participants who had a ≤13.5-day history of acute coronary syndrome (ACS). One study included patients with both ACS and chronic coronary syndrome. The follow-up of studies ranged from 3 days to 22.6 months. RESULTS: The use of colchicine in patients who underwent PCI significantly reduced MACE outcomes (risk ratio 0.73 (95% CI 0.61 to 0.87); p=0.0003) with minimal heterogeneity across the analysis (I2=6%; P for Cochran Q=0.38). These results were driven mainly by the reduction in repeat vessel revascularisation, stroke and stent thrombosis. The number needed to treat to prevent one occurrence of MACE was 41. CONCLUSION: Colchicine significantly reduced the risk of MACE in patients with CAD who underwent PCI, mostly in the reduction of repeat vessel revascularisation, stroke and stent thrombosis. The efficacy of colchicine should be further studied by distinguishing its use alongside different stent types and dosing regimens. PROSPERO REGISTRATION NUMBER: CRD42021245699.

Evaluation of Depilatory Agents in the Treatment of Hair-Thread Tourniquet Syndrome.

Background Hair-thread tourniquet syndrome (HTTS) is the constriction of an appendage or tissue by a hair thread, which can cause ischemia and necrosis of distal tissues. Depilatory agents have the potential to release the hair tourniquet without exposing the patient to the risks of surgery. OBJECTIVES: This review aims to evaluate the effectiveness, benefits, complications, and contraindications of depilatory agents in HTTS. METHODS: Relevant terms to HTTS and depilatory agents were used to search for articles on MEDLINE and EMBASE databases using the NHS Healthcare Databases Advanced Search engine. RESULTS: In total, 19 of the 295 articles identified in the primary search were included in the final review. Articles described the benefits of depilatory agents as painless, well tolerated, and non-invasive. Contraindications described include use on mucosal membranes, non-hair tourniquet, and allergy. Sixty-four percent (n = 55) of patients had resolution of their HTTS after one or two cycles of depilatory agent treatment. CONCLUSIONS: The use of depilatory agents has multiple potential benefits. The authors propose a treatment algorithm for the use of depilatory agents in HTTS and recommend that all acute centers should store and train staff in their use.

CD38 is Required for Dendritic Organization in Visual Cortex and Hippocampus.

Morphological screening of mouse brains with known behavioral deficits can give great insight into the relationship between brain regions and their behavior. Oxytocin- and CD38-deficient mice have previously been shown to have behavioral phenotypes, such as restrictions in social memory, social interactions, and maternal behavior. CD38 is reported as an autism spectrum disorder (ASD) candidate gene and its behavioral phenotypes may be linked to ASD. To address whether these behavioral phenotypes relate to brain pathology and neuronal morphology, here we investigate the morphological changes in the CD38-deficient mice brains, with focus on the pathology and neuronal morphology of the cortex and hippocampus, using Nissl staining, immunohistochemistry, and Golgi staining. No difference was found in terms of cortical layer thickness. However, we found abnormalities in the number of neurons and neuronal morphology in the visual cortex and dentate gyrus (DG). In particular, there were arborisation differences between CD38-/- and CD38+/+ mice in the apical dendrites of the visual cortex and hippocampal CA1 pyramidal neurons. The data suggest that CD38 is implicated in appropriate development of brain regions important for social behavior.