Retraction Note: Prevalence of prescribed opioid claims among persons with nontraumatic spinal cord dysfunction in Ontario, Canada: a population-based retrospective cohort study
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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.
Pluvial flood impacts and policyholder responses throughout the United States
Pluvial floods pose a significant threat to properties, yet comprehensive impact analysis is hindered by data limitations on pluvial inundation. To assess pluvial flood impacts, we leveraged U.S. flood insurance claims and policy records for a subset of properties outside 100-year floodplains, streamflow records, and nationwide precipitation data, enabling us to distinguish damage claims caused by pluvial floods over 1978–2021. Strikingly, 87.1% of the claims analyzed from this subset were due to pluvial floods. Utilizing these pluvial flood claims unveiled distinct regional patterns of pluvial impacts across the contiguous U.S. These patterns are informed by the relationship between claim frequency and precipitation within each region. Remarkably, despite the pervasiveness of impacts, many states are seeing declining uptake in pluvial flood insurance coverage. Our study highlights regions facing heightened pluvial flood risks and underscores the critical need for enhanced consideration of pluvial inundation within risk management frameworks.
Product and trial design considerations on the path towards a vaccine to combat opioid overdose
Opioid overdose deaths are an evolving public health emergency in the United States. Recent advancements in drug conjugate vaccine design and adjuvantation technologies have re-ignited interest in the potential clinical utility of opioid vaccination. Here we present the concept of fentanyl vaccination as a complementary strategy for opioid overdose prevention with a focus on vaccine safety, efficacy, and considerations for vaccine development and testing in early phase human clinical trials.
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.
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