Treatments of fatigue after spinal cord injury: a systematic review and meta-analysis
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A systematic review of digital and imaging technologies for measuring fatigue in immune mediated inflammatory diseases
Chronic fatigue greatly impacts the quality of life in individuals with immune-mediated inflammatory disease (IMID). Currently, fatigue assessment relies on patient-reported outcome (PRO) questionnaires. A systematic review following PRISMA guidelines was conducted to explore how digital and imaging technologies have been used to measure fatigue. PubMed and Cochrane Library were searched from 2003 to June 2023. Study quality was assessed using the STROBE checklist for observational studies. The database search identified 1541 studies; 16 were selected for inclusion, including three clinical trial reports. Disease cohorts included in this review were rheumatoid arthritis, primary Sjögren’s syndrome, systemic lupus erythematosus, and inflammatory bowel disease. The majority of the studies found significant associations between fatigue, as assessed by PROs, and various digital and imaging endpoints. However, the studies were limited by a small sample size and short duration. This review stresses the need for additional research on fatigue using innovative digital and imaging modalities.
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.
No evidence for decision fatigue using large-scale field data from healthcare
Decision fatigue is the idea that making decisions is mentally demanding and eventually leads to deteriorated decision quality. Many studies report results that appear consistent with decision fatigue. However, most of this evidence comes from observed sequential patterns using retrospective designs, without preregistration or external validation and with low precision in how decision fatigue is operationalized. Here we conducted an empirical test of decision fatigue using large-scale, high-resolution data on healthcare professionals’ medical judgments at a national telephone triage and medical advice service. This is a suitable setting for testing decision fatigue because the work is both hard and repetitive, yet qualified, and the variation in scheduling produced a setting where level of fatigue could be regarded as near random for some segments of the data. We hypothesized increased use of heuristics, more specifically convergence toward personal defaults in case judgments, and higher assigned urgency ratings with fatigue. We tested these hypotheses using one-sided Bayes Factors computed from underlying Bayesian generalized mixed models with random intercepts. The results consistently showed relative support for the statistical null hypothesis of no difference in decision-making depending on fatigue (BF0+ > 22 for all main tests). We thus found no evidence for decision fatigue. Whereas these results don’t preclude the existence of a weaker or more nuanced version of decision fatigue or more context-specific effects, they cast serious doubt on the empirical relevance of decision fatigue as a domain general effect for sequential decisions in healthcare and elsewhere.
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.
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