PubMed · 13066011
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W S MCCUNE, A SAMADI, B BLADES. 1953. Experimental aneurysms.. https://doi.org/10.1097/00000658-195308000-00007
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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.
BACKGROUND: The aim of this study was to describe early and late results of proximal and distal ligation for popliteal aneurysm (PA), combined with bypass, with particular reference to the fate of the excluded aneurysm. METHODS: Of a cohort of 116 patients with PAs, 66 were treated with bypass and ligation. Graft patency was determined by duplex surveillance. In addition, 17 patients with bypassed PAs underwent a total of 33 duplex scans to determine flow within the aneurysm and change in size. RESULTS: For initially patent PAs, 3-, 5- and 8-year primary bypass graft patency was 78, 78 and 51 per cent respectively. These rates were not statistically significantly different from those following bypass for thrombosed PA, 3- and 5-year primary patency being 72 and 65 per cent respectively. No PA produced further symptoms after bypass and ligation. No flow was seen in any aneurysm at follow-up. Only one showed an increase in size. CONCLUSION: Proximal and distal ligation with bypass produced satisfactory long-term patency with good exclusion of the PA.
A 10-year-old girl developed recurrent bouts of massive hemoptysis over a 9-month period. No obvious bleeding source was detected. Her pulmonary angiogram showed a pulmonary aneurysm of the second branch of the left main pulmonary artery as well as widespread irregularities of the pulmonary arteries including areas of stenosis and pruning. Elective embolization of the aneurysm did not control hemoptysis and emergency left upper lobectomy had to be performed. Histology showed large artery wall injury with acute leucocytoclastic inflammation, fibrinoid necrosis, granulomatous inflammation, and ectasia of vessel wall. This combination of abnormalities has not been described to date and represents the first case of isolated pulmonary arteritis in children prior to puberty.