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MedRxiv : the Preprint Server For... Jun 2024Acute SARS-CoV-2 infection triggers the generation of diverse and functional autoantibodies (AABs), even after mild cases. Persistently elevated autoantibodies have been...
Acute SARS-CoV-2 infection triggers the generation of diverse and functional autoantibodies (AABs), even after mild cases. Persistently elevated autoantibodies have been found in some individuals with long COVID (LC). Using a >21,000 human protein array, we identified diverse AAB targets in LC patients that correlated with their symptoms. Elevated AABs to proteins in the nervous system were found in LC patients with neurocognitive and neurological symptoms. Purified Immunoglobulin G (IgG) samples from these individuals reacted with human pons tissue and were cross-reactive with mouse sciatic nerves, spinal cord, and meninges. Antibody reactivity to sciatic nerves and meninges correlated with patient-reported headache and disorientation. Passive transfer of IgG from patients to mice led to increased sensitivity and pain, mirroring patient-reported symptoms. Similarly, mice injected with IgG showed loss of balance and coordination, reflecting donor-reported dizziness. Our findings suggest that targeting AABs could benefit some LC patients.
PubMed: 38947091
DOI: 10.1101/2024.06.18.24309100 -
Clinical Toxicology (Philadelphia, Pa.) Jul 2024Tralopyril is a metabolite of the pesticide chlorfenapyr. Direct toxicity by tralopyril has not been described. We report two cases of tralopyril poisoning via...
INTRODUCTION
Tralopyril is a metabolite of the pesticide chlorfenapyr. Direct toxicity by tralopyril has not been described. We report two cases of tralopyril poisoning via inhalation.
CASE PRESENTATIONS
Two workers developed heat intolerance, diaphoresis, and weight loss after occupational inhalational exposure to tralopyril. The exposure was due to the absence of respiratory protection. Magnetic resonance imaging showed abnormal signals in the bilateral periventricular white matter, corpus callosum, basal ganglia, brainstem, and spinal cord. The patient's blood tralopyril concentrations on days 1, 3, 5, 8, and 11 post-admission were 1.09 mg/L, 1.04 mg/L, 1.01 mg/L, 0.71 mg/L, and 0.313 mg/L, respectively. Haemoperfusion (HA330), haemoperfusion (HA380), and haemodiafiltration were performed on days 1-3, 5-8, and 9-10, respectively. The patient's symptoms followed inappropriate use of respiratory protection. His blood tralopyril concentrations on days 1, 4, 5, and 6 were 0.592 mg/L, 0.482 mg/L, 0.370 mg/L, and 0.228 mg/L, respectively.
DISCUSSION
The patients presented with features typical of chlorfenapyr poisoning, which suggests that tralopyril is the main toxic metabolite of chlorfenapyr.
CONCLUSION
Tralopyril can be absorbed by inhalation, leading to delayed clinical symptoms and organ damage, including toxic encephalopathy and spinal cord damage.
PubMed: 38946483
DOI: 10.1080/15563650.2024.2370319 -
Molecular Ecology Jun 2024Organisms adapt to daily and seasonal environmental changes to maximise their metabolic and reproductive fitness. For seasonally breeding animals, photoperiod is... (Review)
Review
Organisms adapt to daily and seasonal environmental changes to maximise their metabolic and reproductive fitness. For seasonally breeding animals, photoperiod is considered the most robust cue to drive these changes. It, however, does not explain the interannual variations in different seasonal phenotypes. Several studies have repeatedly shown the influence of ambient temperature on the timing of different seasonal physiologies including the timing of migration, reproduction and its associated behaviours, etc. In the present review, we have discussed the effects of changes in ambient temperature on different seasonal events in endotherms with a focus on migratory birds as they have evolved to draw benefits from distinct but largely predictable seasonal patterns of natural resources. We have further discussed the physiological and molecular mechanisms by which temperature affects seasonal timings. The primary brain area involved in detecting temperature changes is the hypothalamic preoptic area. This area receives thermal inputs via sensory neurons in the peripheral ganglia that measure changes in thermoregulatory tissues such as the skin and spinal cord. For the input signals, several thermal sensory TRP (transient receptor potential ion channels) channels have been identified across different classes of vertebrates. These channels are activated at specific thermal ranges. Once perceived, this information should activate an effector function. However, the link between temperature sensation and the effector pathways is not properly understood yet. Here, we have summarised the available information that may help us understand how temperature information is translated into seasonal timing.
PubMed: 38946196
DOI: 10.1111/mec.17447 -
Retrovirology Jul 2024Since the introduction of combination antiretroviral therapy (cART) the brain has become an important human immunodeficiency virus (HIV) reservoir due to the relatively...
BACKGROUND
Since the introduction of combination antiretroviral therapy (cART) the brain has become an important human immunodeficiency virus (HIV) reservoir due to the relatively low penetration of many drugs utilized in cART into the central nervous system (CNS). Given the inherent limitations of directly assessing acute HIV infection in the brains of people living with HIV (PLWH), animal models, such as humanized mouse models, offer the most effective means of studying the effects of different viral strains and their impact on HIV infection in the CNS. To evaluate CNS pathology during HIV-1 infection in the humanized bone marrow/liver/thymus (BLT) mouse model, a histological analysis was conducted on five CNS regions, including the frontal cortex, hippocampus, striatum, cerebellum, and spinal cord, to delineate the neuronal (MAP2ab, NeuN) and neuroinflammatory (GFAP, Iba-1) changes induced by two viral strains after 2 weeks and 8 weeks post-infection.
RESULTS
Findings reveal HIV-infected human cells in the brain of HIV-infected BLT mice, demonstrating HIV neuroinvasion. Further, both viral strains, HIV-1 and HIV-1, induced neuronal injury and astrogliosis across all CNS regions following HIV infection at both time points, as demonstrated by decreases in MAP2ab and increases in GFAP fluorescence signal, respectively. Importantly, infection with HIV-1 had more prominent effects on neuronal health in specific CNS regions compared to HIV-1 infection, with decreasing number of NeuN neurons, specifically in the frontal cortex. On the other hand, infection with HIV-1 demonstrated more prominent effects on neuroinflammation, assessed by an increase in GFAP signal and/or an increase in number of Iba-1 microglia, across CNS regions.
CONCLUSION
These findings demonstrate that CNS pathology is widespread during acute HIV infection. However, neuronal loss and the magnitude of neuroinflammation in the CNS is strain dependent indicating that strains of HIV cause differential CNS pathologies.
Topics: Animals; Mice; HIV-1; HIV Infections; Humans; Neurons; Neuroinflammatory Diseases; Disease Models, Animal; Brain; Glial Fibrillary Acidic Protein; Calcium-Binding Proteins; Microfilament Proteins
PubMed: 38945996
DOI: 10.1186/s12977-024-00644-z -
Magnetic Resonance in Medical Sciences... 2024This special issue of Magnetic Resonance in Medical Sciences is dedicated to "Advanced Techniques for MR Neuroimaging," featuring nine review articles authored by...
This special issue of Magnetic Resonance in Medical Sciences is dedicated to "Advanced Techniques for MR Neuroimaging," featuring nine review articles authored by leading experts. The reviews cover advancements in reproducible research practices, diffusion tensor imaging along the perivascular space, myelin imaging using magnetic susceptibility source separation, spinal cord quantitative MRI analysis, tractometry of visual white matter pathways, deep learning-based image enhancement, arterial spin labeling, the potential of radiomics, and MRI-based quantification of brain oxygen metabolism. These articles provide a comprehensive update on cutting-edge technologies and their applications in clinical and research settings, highlighting their impact on improving diagnostic accuracy and understanding of neurological disorders.
Topics: Humans; Neuroimaging; Magnetic Resonance Imaging; Brain; Diffusion Tensor Imaging; Image Processing, Computer-Assisted; Nervous System Diseases; Deep Learning
PubMed: 38945942
DOI: 10.2463/mrms.e.2024-1000 -
Clinical Radiology Jun 2024Spinal muscular atrophy (SMA) is an autosomal recessive genetic disease caused by the degeneration of the α-motor neurons in the anterior horn of the spinal cord. SMA... (Review)
Review
Spinal muscular atrophy (SMA) is an autosomal recessive genetic disease caused by the degeneration of the α-motor neurons in the anterior horn of the spinal cord. SMA is clinically characterized by progressive and symmetrical muscle weakness and muscle atrophy and ends up with systemic multisystem abnormalities. Quantitative MRI (qMRI) has the advantages of non-invasiveness, objective sensitivity, and high reproducibility, and has important clinical value in evaluating the severity of neuromuscular diseases and monitoring the efficacy of treatment. This article summarizes the clinical use of muscular MRI and magnetic resonance neurography in assessing the progress of SMA.
PubMed: 38945793
DOI: 10.1016/j.crad.2024.06.004 -
Environmental Research Jun 2024Tail resorption during amphibian metamorphosis is one of the most dramatic processes that is obligatorily dependent on thyroid hormone (TH). Heavy metals could result in...
Tail resorption during amphibian metamorphosis is one of the most dramatic processes that is obligatorily dependent on thyroid hormone (TH). Heavy metals could result in thyroid gland damages and disturb TH homeostasis. Lead (Pb) and copper (Cu) often co-exist in natural aquatic ecosystems. However, there is still little information on how tail resorption responds to alone or combined exposure to Pb and Cu. Our study investigated the effects of Pb and Cu alone or combined exposure on the morphological parameters of the tail, histological changes of thyroid gland and tail, and gene expression programs involved in cell death of the tail in Bufo gargarizans tadpoles at the climax of metamorphosis. Results demonstrated that Pb, Cu and Pb-Cu mixture exposure resulted in a significantly longer tail compared with control. Damages to notochord, muscle, skin and spinal cord of the tail were found in Pb and Cu exposure groups. The colloid area, the height of follicular cells and number of phagocytic vesicles of thyroid gland in Pb-Cu mixture exposure groups were significantly reduced. In addition, the expression levels of TH, apoptosis, autophagy, degradation of cellular components and oxidative stress-related genes in the tail were significantly altered following Pb and Cu exposure. The present work revealed the relationship between environmental pollutants and tail resorption, providing scientific basis for amphibian protection.
PubMed: 38945509
DOI: 10.1016/j.envres.2024.119505 -
Journal of Stroke and Cerebrovascular... Jun 2024transient ischemic attack (TIA) is defined as a transient episode of neurological dysfunction caused by focal brain, spinal cord, or retinal ischemia, with clinical...
PURPOSE
transient ischemic attack (TIA) is defined as a transient episode of neurological dysfunction caused by focal brain, spinal cord, or retinal ischemia, with clinical symptoms typically lasting less than one hour, and without evidence of acute infarction. In this type of ischemic event, there are no data about a possible cardiac injury tested with troponin. After a stroke, it is well established the cardiac involvement due to a neuro-inflammatory response (recently defined as Stroke Heart Syndrome). The aim of this study is to compare the troponin elevation after a stroke with TIA.
MATERIALS AND METHODS
this is a retrospective, single center study on 565 patients (73 TIAs, 492 stroke). We collected demographic characteristics, cardiovascular risk factors, cardiac data such as troponin, NT-proBNP, left atrial dilatation, etiology of the ischemic event (TOAST classification).
RESULTS
we compare IS and TIA for each TOAST subtype. In all groups no substantial differences were found in demographic and past medical history (p>0.05). However, the maximum troponin level reached were significantly lower in TIAs than IS (p<0.05), except in lacunar etiology were troponin elevation was low also in IS group. We found a trend in favor to IS in the rise and fall troponin elevation over 30% in all the TOAST subgroups, but only in the cryptogenic etiology the difference was significant. About the others cardiac markers of injury, a significant higher rate of elevated NT-proBNP was found in the IS cohort.
CONCLUSIONS
troponin level after TIAs is significantly lower than after IS. Troponin elevation after an ischemic event may be more relevant in patients with higher NT-proBNP levels and older age. More studies are needed to better understand the patho-physiology of this phenomenon after an ischemic event.
PubMed: 38945415
DOI: 10.1016/j.jstrokecerebrovasdis.2024.107844 -
The Lancet. Neurology Jun 2024
PubMed: 38945143
DOI: 10.1016/S1474-4422(24)00260-6 -
The Lancet. Neurology Jun 2024The accuracy of prognostication in patients with cervical spinal cord injury (SCI) needs to be improved. We aimed to explore the prognostic value of preserved spinal...
BACKGROUND
The accuracy of prognostication in patients with cervical spinal cord injury (SCI) needs to be improved. We aimed to explore the prognostic value of preserved spinal tissue bridges-injury-spared neural tissue adjacent to the lesion-for prediction of sensorimotor recovery in a large, multicentre cohort of people with SCI.
METHODS
For this longitudinal study, we included patients with acute cervical SCI (vertebrae C1-C7) admitted to one of three trauma or rehabilitation centres: Murnau, Germany (March 18, 2010-March 1, 2021); Zurich, Switzerland (May 12, 2002-March 2, 2019); and Denver, CO, USA (Jan 12, 2010-Feb 16, 2017). Patients were clinically assessed at admission (baseline), at discharge (3 months), and at 12 months post SCI. Midsagittal tissue bridges were quantified from T2-weighted images assessed at 3-4 weeks post SCI. Fractional regression and unbiased recursive partitioning models, adjusted for age, sex, centre, and neurological level of injury, were used to assess associations between tissue bridge width and baseline-adjusted total motor score, pinprick score, and light touch scores at 3 months and 12 months. Patients were stratified into subgroups according to whether they showed better or worse predicted recovery.
FINDINGS
The cohort included 227 patients: 93 patients from Murnau (22 [24%] female); 43 patients from Zurich (four [9%] female); and 91 patients from Denver (14 [15%] female). 136 of these participants (from Murnau and Zurich) were followed up for up to 12 months. At 3 months, per preserved 1 mm of tissue bridge at baseline, patients recovered a mean of 9·3% (SD 0·9) of maximal total motor score (95% CI 7·5-11.2), 8·6% (0·8) of maximal pinprick score (7·0-10·1), and 10·9% (0·8) of maximal light touch score (9·4-12·5). At 12 months post SCI, per preserved 1 mm of tissue bridge at baseline, patients recovered a mean of 10·9% (1·3) of maximal total motor score (8·4-13·4), 5·7% (1·3) of maximal pinprick score (3·3-8·2), and 6·9% (1·4) of maximal light touch score (4·1-9·7). Partitioning models identified a tissue bridge cutoff width of 2·0 mm to be indicative of higher or lower 3-month total motor, pinprick, and light touch scores, and a cutoff of 4·0 mm to be indicative of higher and lower 12-month scores. Compared with models that contained clinical predictors only, models additionally including tissue bridges had significantly improved prediction accuracy across all three centres.
INTERPRETATION
Tissue bridges, measured in the first few weeks after SCI, are associated with short-term and long-term clinical improvement. Thus, tissue bridges could potentially be used to guide rehabilitation decision making and to stratify patients into more homogeneous subgroups of recovery in regenerative and neuroprotective clinical trials.
FUNDING
Wings for Life, International Foundation for Research in Paraplegia, EU project Horizon 2020 (NISCI grant), and ERA-NET NEURON.
PubMed: 38945142
DOI: 10.1016/S1474-4422(24)00173-X