Dural arteriovenous fistulas involving the superior sagittal and parasagittal sinuses: clinical presentation, imaging characteristics and treatment strategies.

BACKGROUND AND PURPOSE: Dural arteriovenous fistulas (DAVFs) involving the superior sagittal (SSS) and parasagittal sinuses are often inappropriately classified. We explore the clinical presentations, imaging characteristics and endovascular treatment strategies these two DAVF subtypes. MATERIALS AND METHODS: Clinical and imaging data of 19 patients with SSS or parasagittal sinus DAVFs who underwent endovascular treatment in our institution from 2017 and 2022 were retrospectively analyzed. The angiographic findings, endovascular treatment strategies and angiographic outcomes were evaluated and recorded. RESULTS: Among these 19 patients, 14 had a parasagittal DAVF, 4 had a SSS DAVF, one patient had both a parasagittal and SSS DAVF. Only one (1/19, 5.26%) patient presented with intracranial haemorrhage (ICH); For the parasagittal DAVF group, most of the shunts were located along the middle third of the SSS (12/15, 80%), on the dura in proximity with the junctional zone between the bridging vein and SSS (15/15, 100%), with ipsilateral cortical venous reflux (CVR) (15/15, 100%). For the SSS DAVF group, all 5 patients had shunting zone along the middle third of the SSS, on the sinus or parasinus wall, with bilateral CVR. Trans-arterial embolization, via the middle meningeal artery (MMA) as the primary route of access, was the primary treatment approach in 95% of cases (19/20). Reflux of embolization material into the SSS was observed in one case (1/5, 20%) of SSS DAVF in which balloon sinus protection was not used during embolization. CONCLUSIONS: Our study found that parasagittal DAVFs have shunting point(s) centred on the junctional zone of the bridging vein and the SSS with ipsilateral CVR, while SSS DAVFs have shunting point(s) centred on the sinus or parasinus wall with bilateral CVR. Trans-arterial embolization via the MMA(s) can be used as the primary treatment strategy in most cases. Balloon sinus protection during embolization is not necessary in cases of parasagittal DAVF with occluded or stenosed connection with the SSS but its use should be considered in cases of SSS DAVF with patent sinus. ABBREVIATIONS: DAVF, Dural arteriovenous fistula; SSS, Superior sagittal sinus; CVR, Cortical venous reflux; MMA, middle meningeal artery; ICH, Intracranial haemorrhage; STA, Superficial temporal artery; OA, Occipital artery. CFD, Computational fluid dynamics.

A Hydrothermal-Sedimentary Context for the Origin of Life.

Critical to the origin of life are the ingredients of life, of course, but also the physical and chemical conditions in which prebiotic chemical reactions can take place. These factors place constraints on the types of Hadean environment in which life could have emerged. Many locations, ranging from hydrothermal vents and pumice rafts, through volcanic-hosted splash pools to continental springs and rivers, have been proposed for the emergence of life on Earth, each with respective advantages and certain disadvantages. However, there is another, hitherto unrecognized environment that, on the Hadean Earth (4.5-4.0 Ga), would have been more important than any other in terms of spatial and temporal scale: the sedimentary layer between oceanic crust and seawater. Using as an example sediments from the 3.5-3.33 Ga Barberton Greenstone Belt, South Africa, analogous at least on a local scale to those of the Hadean eon, we document constant permeation of the porous, carbonaceous, and reactive sedimentary layer by hydrothermal fluids emanating from the crust. This partially UV-protected, subaqueous sedimentary environment, characterized by physical and chemical gradients, represented a widespread system of miniature chemical reactors in which the production and complexification of prebiotic molecules could have led to the origin of life. Key Words: Origin of life-Hadean environment-Mineral surface reactions-Hydrothermal fluids-Archean volcanic sediments. Astrobiology 18, 259-293.

Binding assays of inhibitors towards selected V-ATPase domains.

The macrolide antibiotic bafilomycin and the related synthetic compound SB 242784 are potent inhibitors of the vacuolar H+ -ATPases (V-ATPase). It is currently believed that the site of action of these inhibitors is located on the membrane bound c-subunits of V-ATPases. To address the identification of the critical inhibitors binding domain, their specific binding to a synthetic peptide corresponding to the putative 4th transmembrane segment of the c-subunit was investigated using fluorescence resonance energy transfer (FRET), and for this purpose a specific formalism was derived. Another peptide of the corresponding domain of the c' isoform, was checked for binding of bafilomycin, since it is not clear if V-ATPase inhibition can also be achieved by interaction of the inhibitor with the c'-subunit. It was concluded that bafilomycin binds to the selected peptides, whereas SB 242784 was unable to interact, and in addition for bafilomycin, its interaction with the peptides either corresponding to the c- or the c'-subunit isoforms is identical. Since the observed interactions are however much weaker as compared to the very efficient binding of both bafilomycin and SB 242784 to the whole protein, it can be concluded that assembly of all V-ATPase transmembrane segments is required for an efficient interaction.

Interaction of the indole class of vacuolar H(+)-ATPase inhibitors with lipid bilayers.

The selective inhibitor of osteoclastic V-ATPase (2Z,4E)-5-(5,6-dichloro-2-indolyl)-2-methoxy-N-(1,2,2,6,6-pentamethylpiperidin-4-yl)-2,4-pentadienamide (SB 242784), member of the indole class of V-ATPase inhibitors, is expected to target the membrane-bound domain of the enzyme. A structural study of the interaction of this inhibitor with the lipidic environment is an essential step in the understanding of the mechanism of inhibition. In this work, a comprehensive study of the relevant features of this interaction was performed. Inhibitor partition coefficients to lipid vesicles as well as its transverse location, orientation (order parameters), and dynamics while bound to bilayers were determined through photophysical techniques, taking advantage of the intrinsic fluorescence of the molecule. To better evaluate the functionally relevant features of SB 242784, a second inhibitor, INH-1, from the same class and having a reduced activity was also examined. It is shown that regarding membrane interaction their properties remain very similar for both molecules, suggesting that the differences in inhibition efficiencies are solely a consequence of the molecular recognition processes within the inhibition site in the V-ATPase.