Articles: function.
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To better understand the relationships among treatment, pain, and physical function (PF). ⋯ At least 75% of the treatment effect of tanezumab on physical functioning can be explained by the improvements in pain. However, tanezumab had an additional effect on physical functioning (~25%) that, was independent of improvements in pain. Such independent effects are of considerable interest and require further research to determine their mechanisms.
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Fetal growth restriction (FGR) is associated with a suboptimal intrauterine environment, which may adversely impact fetal neurodevelopment. However, analysing neurodevelopmental outcomes by observed birthweight fails to differentiate between true FGR and constitutionally small infants and cannot account for iatrogenic intervention. This study aimed to determine the relationship between antenatal FGR and mid-childhood (age 5 to 7 years) educational outcomes. ⋯ Compared to children with normal fetal growth and no markers of placental dysfunction, FGR is associated with poorer educational attainment in mid-childhood.
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Anesthesia and analgesia · Apr 2023
Ketamine Induces Delirium-Like Behavior and Interferes With Endosomal Tau Trafficking.
Ketamine is an intravenous anesthetic. However, whether ketamine can induce neurotoxicity and neurobehavioral deficits remains largely unknown. Delirium is a syndrome of acute brain dysfunction associated with anesthesia and surgery in patients, and tau protein may contribute to postoperative delirium. Finally, ketamine may affect the function of the endosome, the key organelle for tau release from neurons. Therefore, we set out to determine the effects of ketamine on delirium-like behavior in mice and on tau trafficking in cultured cells. ⋯ These data suggest that ketamine may interfere with intracellular tau trafficking and induce delirium-like behavior, promoting future research regarding the potential neurotoxicity of anesthetics.
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The anterior cingulate cortex (ACC) processes the affective component of pain, whereas the primary somatosensory cortex (S1) is involved in its sensory-discriminative component. Injection of morphine in the ACC has been reported to be analgesic, and endogenous opioids in this area are required for pain relief. Mu opioid receptors (MORs) are expressed in both ACC and S1; however, the identity of MOR-expressing cortical neurons remains unknown. ⋯ Our results suggest a differential contribution of MOR-mediated modulation to ACC and S1 outputs. We also found that females had a greater density of MOR+ neurons compared with males in both areas. In summary, we conclude that MOR-dependent opioidergic signaling in the cortex displays sexual dimorphisms and likely evolved to meet the distinct function of pain-processing circuits in limbic and sensory cortical areas.
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CD36 is a transmembrane glycoprotein receptor for oxidized low density lipoprotein (LDL) and other endogenous danger signals and promotes athero-thrombotic processes. CD36 has been shown to associate physically with other transmembrane proteins, including integrins, tetraspanins, and toll-like receptors, which modulate CD36-mediated cell signaling. The CD36 N-terminal transmembrane domain (nTMD) contains a GXXXG sequence motif that mediates protein-protein interactions in many membrane proteins. ⋯ Prior to performing these assays, cells were incubated with a synthetic 29 amino acid peptide containing the 22 amino acid of CD36 nTMD or a control peptide in which the glycine residues in GXXXG motif were replaced by valines. In functional experiments, macrophages were preincubated with peptides and then treated with oxLDL to assess LDL uptake, foam cell formation, ROS formation and cell migration. CD36 nTMD peptide treated cells compared to untreated or control peptide treated cells showed decreased CD36 surface associations with tetraspanin CD9 and ameliorated pathologically important CD36 mediated responses to oxLDL, including uptake of DiI-labeled oxLDL, foam cell formation, ROS generation, and inhibition of migration.