Aneurismal subarachnoid hemorrhage (SAH) is an extremely severe illness associated with a high mortality rate and permanent severe neurological dysfunction in two-thirds of all affected patients. One of the major complications of SAH is vasospasm-associated cerebral ischemia. Clinical and experimental data suggest that vasospasm is linked to the inflammatory response associated with SAH. The goal of this study was to investigate the expression of Pentraxin3 (PTX3), a prototypic long pentraxin protein induced by proinflammatory signals in the brain, in SAH patients to test the hypothesis that SAH is followed by an upregulation of PTX3, and establish a temporal relationship between the expression of PTX3 and the induction of vasospasm. We also attempted to establish that PTX3 is detectable in cerebrospinal fluid (CSF).

The established culture consisted of a morphologically homogeneous cell population belonging to a monocytic lineage having some features of an osteoclast-like cell type. Cells had an invasive phenotype, were angiogenic, and produced osteoclastogenic (IL-6, TGF-beta1, IL-1beta) and angiogenic (vascular endothelial growth factor-A [VEGF-A], CXCL-8) molecules when challenged with inflammatory cytokines. Immunodeficient mice injected with these cells did not show any bone lesions or vascular alteration, but had high amounts of circulating human IL-6 and VEGF-A. Cells isolated from a cutaneous lymphangiomatosis did not show any of these findings. These data suggest that cells of monocyte-macrophage lineage play an essential role in the pathogenesis of Gorham-Stout disease, whose progression is propelled by cytokine circuits that accelerate angiogenesis and osteoclastogenesis.

The prototypic long pentraxin PTX3 is a unique fluid-phase pattern recognition receptor that plays a nonredundant role in innate immunity and female fertility. The PTX3 C-terminal domain is required for C1q recognition and complement activation and contains a single N-glycosylation site on Asn 220. In the present study, we characterized the structure of the human PTX3 glycosidic moiety and investigated its relevance in C1q interaction and activation of the complement classical pathway. By specific endo and exoglycosidases digestion and direct mass spectrometric analysis, we found that both recombinant and naturally occurring PTX3 were N-linked to fucosylated and sialylated complex-type sugars. Interestingly, glycans showed heterogeneity mainly in the relative amount of bi, tri, and tetrantennary structures depending on the cell type and inflammatory stimulus. Enzymatic removal of sialic acid or the entire glycosidic moiety equally enhanced PTX3 binding to C1q compared to that in the native protein, thus indicating that glycosylation substantially contributes to modulate PTX3/C1q interaction and that sialic acid is the main determinant of this contribution. BIAcore kinetic measurements returned decreasing K(off) values as sugars were removed, pointing to a stabilization of the PTX3/C1q complex. No major rearrangement of PTX3 quaternary structure was observed after desialylation or deglycosylation as established by size exclusion chromatography. Consistent with C1q binding, PTX3 desialylation enhanced the activation of the classical complement pathway, as assessed by C4 and C3 deposition. In conclusion, our results provided evidence of an involvement of the PTX3 sugar moiety in C1q recognition and complement activation.

This study derived 2 simple models that predict the risk of a psychiatric adverse effect from levetiracetam. These algorithms can be used to guide prescription in clinical practice.

We appreciate the thoughtful feedback and points raised by authors Moulton, Norton, Powell, Mohamedali and Hopkins regarding the temporality between depression and inflammatory bowel disease (IBD) diagnosis and recommendation to perform further sensitivity analyses.1 The authors correctly highlight that the prodromal effects of IBD, including fatigue and low mood, prior to diagnosis may mimic depression and therefore put temporality into question.2 Furthermore, the median time from Crohn’s disease symptom presentation to diagnosis is 9 months and 75% of patients are diagnosed within 2 years.3 In response, we have performed two sensitivity analyses restricting to observations with at least (1) 9 months between depression and IBD diagnosis and …

This study highlights the impact of clinical and psychosocial determinants of patient-ratings of migraine severity. GAMS is a brief and valid tool that can be used to assess migraine severity in busy clinical settings.

Maugeri, N., P. Rovere-Querini, M. Slavich, G. Coppi, A. Doni, B. Bottazzi, C. Garlanda, D. Cianflone, A. Maseri, A. Mantovani, and A. A. Manfredi. 2011. Early and transient release of leukocyte pentraxin 3 during acute myocardial infarction. J. Immunol. 187: [970–979][1]. The second institution

CRD42020221662.