Epidemiology of traumatic spinal cord injury in Ireland, 2017–2022
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Pathogenesis of aquatic bird bornavirus 1 in turkeys of different age
Aquatic bird bornavirus 1 (ABBV1), an orthobornavirus in the family Bornaviridae, displays a broad host range among avian species, including poultry. The pathogenesis of orthobornaviruses, at least in mammals and psittacines, appears to be mediated by the host immune response against the infected nervous tissue, with younger animals showing a milder disease due to immune tolerance. Here, we tested the ability of ABBV1 to infect domestic turkeys (Meleagris gallopavo), with a focus on evaluating the impact of age at infection. Cohorts of 6-week-old (old) and day-old (young) male turkeys were divided into virus-inoculated and control groups, and kept for up to 12 weeks. Results showed that turkeys of both ages were susceptible to ABBV1 infection by intramuscular administration, following a centripetal and limited centrifugal spread, although infection appeared delayed in old compared to young birds. Notably, only young turkeys developed clinical signs and more frequent inflammation of the central nervous system, indicating that infection at a very early age is unlikely to induce tolerance to ABBV1 infection.
A genetic perspective on the recent demographic history of Ireland and Britain
While subtle yet discrete clusters of genetic identity across Ireland and Britain have been identified, their recent demographic history is unclear. Using genotype data from 6574 individuals with associated regional Irish or British ancestry, we identified genetic communities by applying Leiden community detection. Using haplotype segments segregated by length as proxy for time, we inferred regional Irish and British demographic histories. Using a subset of Irish participants, we provide genealogical context by estimating the enrichment/depletion of surnames within the Irish genetic communities. Through patterns of haplotype sharing, we find evidence of recent population bottlenecks in Orcadian, Manx and Welsh genetic communities. We observed temporal changes in genetic affinities within and between genetic communities in Ireland and Britain. Structure in Ireland is subtler compared to neighbouring British communities, with the Irish groups sharing relatively more short haplotype segments. In addition, we detected varying degrees of genetic isolation in peripheral Irish and British genetic communities across different time periods. Further, we observe a stable migration corridor between north-east Ireland and south-west Scotland while there is a recent migration barrier between south-east and west Ireland. Genealogical analysis of surnames in Ireland reflects history—Anglo-Norman surnames are enriched in the Wexford community while Scottish and Gallowglass surnames were enriched in the Ulster community. Using these new insights into the regional demographic history of Ireland and Britain across different time periods, we hope to understand the driving forces of rare allele frequencies and disease risk association within these populations.
Different types of cell death and their interactions in myocardial ischemia–reperfusion injury
Myocardial ischemia–reperfusion (I/R) injury is a multifaceted process observed in patients with coronary artery disease when blood flow is restored to the heart tissue following ischemia-induced damage. Cardiomyocyte cell death, particularly through apoptosis, necroptosis, autophagy, pyroptosis, and ferroptosis, is pivotal in myocardial I/R injury. Preventing cell death during the process of I/R is vital for improving ischemic cardiomyopathy. These multiple forms of cell death can occur simultaneously, interact with each other, and contribute to the complexity of myocardial I/R injury. In this review, we aim to provide a comprehensive summary of the key molecular mechanisms and regulatory patterns involved in these five types of cell death in myocardial I/R injury. We will also discuss the crosstalk and intricate interactions among these mechanisms, highlighting the interplay between different types of cell death. Furthermore, we will explore specific molecules or targets that participate in different cell death pathways and elucidate their mechanisms of action. It is important to note that manipulating the molecules or targets involved in distinct cell death processes may have a significant impact on reducing myocardial I/R injury. By enhancing researchers’ understanding of the mechanisms and interactions among different types of cell death in myocardial I/R injury, this review aims to pave the way for the development of novel interventions for cardio-protection in patients affected by myocardial I/R injury.
Brainstem serotonin amplifies nociceptive transmission in a mouse model of Parkinson’s disease
Parkinson’s disease arises from the degeneration of dopaminergic neurons in the substantia nigra pars compacta, leading to motor symptoms such as akinesia, rigidity, and tremor at rest. The non-motor component of Parkinson’s disease includes increased neuropathic pain, the prevalence of which is 4 to 5 times higher than the general rate. By studying a mouse model of Parkinson’s disease induced by 6-hydroxydopamine, we assessed the impact of dopamine depletion on pain modulation. Mice exhibited mechanical hypersensitivity associated with hyperexcitability of neurons in the dorsal horn of the spinal cord (DHSC). Serotonin (5-HT) levels increased in the spinal cord, correlating with reduced tyrosine hydroxylase (TH) immunoreactivity in the nucleus raphe magnus (NRM) and increased excitability of 5-HT neurons. Selective optogenetic inhibition of 5-HT neurons attenuated mechanical hypersensitivity and reduced DHSC hyperexcitability. In addition, the blockade of 5-HT2A and 5-HT3 receptors reduced mechanical hypersensitivity. These results reveal, for the first time, that PD-like dopamine depletion triggers spinal-mediated mechanical hypersensitivity, associated with serotonergic hyperactivity in the NRM, opening up new therapeutic avenues for Parkinson’s disease-associated pain targeting the serotonergic systems.
The clinical evolution of patients with idiopathic spinal cord herniation: a case series
Retrospective case series of 48 patients.
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