PubMed · 13660376
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C ZANDER. 1959-04-04. [Bilateral posttraumatic cavernous aneurysm].. https://pubmed.ncbi.nlm.nih.gov/13660376/
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Claudin-14 (CLDN14) is a key component of tight junctions (TJs) critical for maintaining paracellular barrier function. Variants of CLDN14 have been linked to Vein of Galen malformations (VOGMs), a rare cerebrovascular disorder; however, the molecular mechanisms underlying their pathogenicity remain unknown. Here, we investigate the mechanistic effects of two VOGM-associated mutations, A113P and V143M, using reinforcement-learning driven enhanced sampling molecular dynamics simulations combined with DiffNets-based deep learning and independent trajectory-wide structural analyses. Our analysis reveals that A113P induces broader structural disruption of CLDN14, perturbing paracellular sealing, pore symmetry, and inter-protomer communication, whereas V143M induces structural rearrangements centred around TM3 and the TM3-ECL2 region. In both cases, mutation-specific alterations are observed in structural stability and interfacial organization across oligomeric assemblies. Notably, these effects are qualitatively consistent across different modelled architectures, despite variability in local responses. In the absence of experimentally resolved structures, the structural perturbations reported here provide a mechanistic understanding of how VOGM-associated variants may influence CLDN14 structure and dynamics.
The problem of symptomatic, diffuse coronary artery disease not amenable to the established methods of medical or revascularizing therapies remains unsolved. Aortocoronary venous bypass grafting is a rare treatment modality bearing considerable risks. We report on a further complication of the method.
A case of three pancreaticoduodenal artery (PDA) aneurysms associated with coeliac artery occlusion and a concomitant splenic arterial aneurysm is described. Surgical treatment was used because it was anticipated that the hepatic blood supply would be obstructed completely if percutaneous transluminal embolization for three PDA aneurysms were performed. Splenectomy in continuity with the splenic artery aneurysm and PDA aneurysmectomies were performed, and infrarenal abdominal aorto-splenic artery bypass was accomplished using a 6mm ringed expanded polytetrafluoroethylene graft. The postoperative course was uneventful. Graft patency and successful aneurysm ablation were confirmed using MRA and intravenous DSA. Arterial histology revealed segmental arterial mediolysis. At 2-year follow-up, the patient was well and asymptomatic. A literature review of PDA aneurysms is presented.