Amyloid : the international journal of experimental and clinical investigation : the official journal of the International Society of Amyloidosis
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AGel amyloidosis is a dominantly inherited systemic amyloidosis caused by mutations p. D214N or p. D214Y resulting in gelsolin amyloid (AGel) formation. ⋯ The elastin of elastic fibres in AGel patients was strongly decreased compared to controls. MMP-9 was expressed at lower and TGFβ at higher levels in AGel patients than in controls. The accumulation of amyloid fibrils with severe elastolysis characterises both dermal and vascular derangement in AGel amyloidosis.
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The Curated Protein Aggregation Database (CPAD) is a manually curated and open-access database dedicated to providing comprehensive information related to mechanistic, kinetic and structural aspects of protein and peptide aggregation. The database has been updated to CPAD 2.0 by significantly expanding datasets and improving the user-interface. ⋯ This database will help the scientific community (a) by facilitating research leading to improved understanding of protein aggregation, (b) by helping develop, validate and benchmark mechanistic and kinetic models of protein aggregation, and (c) by assisting experimentalists with design of their investigations and dissemination of data generated by their studies. CPAD 2.0 can be accessed at https://web.iitm.ac.in/bioinfo2/cpad2/index.html.
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We sought to evaluate how PROMIS patient-reported outcome (PRO) measures correlated with disease characteristics in systemic light chain (AL) amyloidosis patients at diagnosis. Newly diagnosed AL patients were recruited at two centres (N = 61). Patients completed the PROMIS Global Health v1.2, PROMIS-29 Profile v2.0 and Fatigue 8a v1.0. ⋯ Physical Function showed the strongest effects across known groups by stage, cardiac involvement and number of organs involved followed by Ability to Participate in Social Roles and Activities. A diagnostic NT-proBNP cut-off of 4200 pg/ml identified patients with moderate/severe PRO scores for these domains. Our results provide evidence for reliability and validity of select PROMIS short form measures in AL amyloidosis at diagnosis.
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Peripheral nerve involvement in immunoglobulin light chain (AL) amyloidosis is common, characterised by severe progressive mixed neuropathy with autonomic dysfunction but there is limited data on the implications and the characteristics of small nerve fibres dysfunction (SNFD). The aim of our prospective study was to evaluate SNFD and its clinical implications in newly diagnosed AL patients. Twenty-three consecutive patients (10 male, mean age 61.78 years) and 21 age- and gender-matched healthy controls (8 male, mean age 61.28 years) underwent clinical evaluation and standard nerve conduction studies (NCS), baroreflex sensitivity (BRS) test, quantitative sensory testing (QST) and skin biopsy at the lower leg for measuring the density of the nerve fibres innervating the epidermis (IENFD). ⋯ BRS index significantly correlated with the IENFD and the QST results while low IENFD was associated with significantly poorer survival. Our study provides new insights and also an initial evaluation of new tools for assessment of the involvement of autonomic and small nerve fibres in AL amyloidosis. These findings also appear to have prognostic implications.