EBioMedicine
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Observational Study
Score Predicting Acute Chest Syndrome During Vaso-occlusive Crises in Adult Sickle-cell Disease Patients.
Vaso-occlusive crisis (VOC), hallmark of sickle-cell disease (SCD), is the first cause of patients' Emergency-Room admissions and hospitalizations. Acute chest syndrome (ACS), a life-threatening complication, can occur during VOC, be fatal and prolong hospitalization. No predictive factor identifies VOC patients who will develop secondary ACS. ⋯ The ACS-predictive score is simple, easily applied and could change VOC management and therapeutic perspectives. Assessed ACS risk could lead to earlier discharges or close monitoring and rapid medical intensification to prevent ACS.
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There is increasing evidence of central hyperexcitability in chronic whiplash-associated disorders (cWAD). However, little is known about how an apparently simple cervical spine injury can induce changes in cerebral processes. ⋯ No differences in rCBF were observed between different levels of electrical stimulation. The alterations in regions directly involved with pain perception and interoceptive processing indicate that cWAD symptoms might be the consequence of a mismatch during the integration of information in brain regions involved in pain processing.
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The innate immune protein Stimulator of interferon genes (STING) promotes the induction of interferon beta (IFN-β) production via the phosphorylation of its C-terminal tail (CTT) by TANK-binding kinase 1 (TBK1). Potent ligands of STING are, therefore, promising candidates for novel anti-cancer drugs or vaccine adjuvants. ⋯ Here, we performed molecular dynamics simulations of the STING fragment containing the CTT in ligand-bound and unbound forms and observed that the binding of a potent ligand cyclic GMP-AMP (cGAMP) induced a local structure in the CTT, reminiscent of the known structure of a TBK1 substrate. The subsequent molecular biological experiments confirmed the observed dynamics of the CTT and identified essential residues for the activation of the IFN-β promoter, leading us to propose a new mechanism of STING activation.