http://repositorio.fleni.org.ar:8080 The DSpace digital repository system captures, stores, indexes, preserves, and distributes digital research material. 2026-10-08T22:20:42Z https://repositorio.fleni.org.ar/xmlui/handle/123456789/1621 Microbiome-derived metabolites from vitamin B2 and B9 pathways modulate MAIT cells from multiple sclerosis patients Correale, Jorge; Marrodán, Mariano; Piedrabuena, María Agustina; Soman, Karthik; Farez, Mauricio Franco; Baranzini, Sergio E. Background: Mucosal-associated invariant T (MAIT) cells recognize microbial vitamin B2 and B9 metabolites via MR1 and have been implicated in multiple sclerosis (MS). How patient-specific gut microbiota shape human MAIT-cell pathogenicity at the clonal level remains unknown.Material and methods: We generated 62 MAIT-cell clones from relapsing-remitting multiple sclerosis (RRMS) patients and 50 from healthy controls (HCs). Clones were stimulated with riboflavin- or folate-pathway metabolites, paraformaldehyde-fixed patient-matched gut bacterial isolates, or interleukin (IL)-12/IL-18. Activation markers, cytokine secretion, cytotoxicity, and competitive MR1-ligand inhibition were assessed. Intestinal permeability was evaluated using I-FABP, LBP, GLP-2, and fecal α-1-antitrypsin. Results: MS-derived MAIT clones showed markedly enhanced activation, increased interferon-gamma (IFN-γ), IL-17, and granulocyte-macrophage colony-stimulating factor (GM-CSF) secretion, and greater cytotoxicity compared with HCs when stimulated with riboflavin-producing taxa isolated from the same patients. Importantly, several responses diverged from predictions based on murine models and genomic inference, including mixed cytokine profiles and graded competitive inhibition by folate-derived ligands. These findings highlight species-specific differences in MR1 ligand handling and MAIT-cell activation. Activation required uptake of intact bacteria and acid-dependent MR1 loading. MS patients exhibited significant intestinal barrier dysfunction, linking dysbiosis to systemic MAIT-cell hyperactivation. Conclusion: At clonal resolution, this study demonstrates that patient-specific microbial metabolism, MR1-ligand competition, and epithelial barrier disruption cooperate to amplify MAIT-cell pathogenicity in MS, revealing human-specific mechanisms not predicted by animal models. 2026-06-01T00:00:00Z https://repositorio.fleni.org.ar/xmlui/handle/123456789/1620 Awareness, attitudes, and barriers toward Transthyretin Amyloid Cardiomyopathy in Latin America: A questionnaire-based cross-sectional study. Camacho-Hubner, Cecilia; Waddington Cruz, Marcia; Rodríguez González, María Juliana; Simões, Marcus Vinicius; López-Ponce de León, Juan David; Fernandes, Fabio; Martínez Carreño, Erika María; Costabel, Juan Pablo; Berríos Bárcenas, Enrique A.; Barroso, Fabio Adrián; Cigarroa López, José Angel; Ortega Reyes, Rosa; Alvarez, Jaime; Pérez de Arenaza, Diego; Buitrago, Diana; Otero, Constanza; Bertoli de Souza, Claudenice Leite; Molina Gómez, Juan Sebastián; Silva Julian, Guilherme Background: Cardiac Amyloidosis (CA), specifically Transthyretin Amyloid Cardiomyopathy (ATTR-CM), is an under-recognized, progressive, and fatal disease. Comprehensive primary data describing awareness, attitudes, and barriers to treatment in Latin America (LATAM) are lacking, highlighting a gap between guidelines and real-world clinical practice. Methods: A cross-sectional, questionnaire-based observational study was conducted among 470 physicians actively involved in patient management across 8 LATAM countries (June-August 2023). The study assessed their awareness, attitudes, and barriers concerning ATTR-CM. Descriptive analysis was performed. Results: Limited knowledge of ATTR-CM was observed. Awareness of its pathophysiology was reported by 50.2%. Patients consulted 4-5 physicians before receiving a confirmed diagnosis. Cardiologists managed most day-to-day cases (76.2%). Transthyretin genetic testing was available to only 26.4%. Local treatment protocols relied on international guidelines (87.4%), with Real-World Data considered important by 60.6%. Patient cost and access to tafamidis were frequently reported barriers. Follow-up commonly relied on echocardiography, NT-pro BNP, NYHA classification, and ECG/Holter ECG. Conclusions: Difficulties in ATTR-CM diagnosis and management in LATAM were influenced by varying knowledge levels, gaps in diagnostic algorithms, and significant access barriers. These factors contribute to delayed diagnosis and management. Enhanced, tailored training strategies and collaborative efforts are necessary to improve early diagnosis, effective treatment, and ultimately, patient outcomes in the region. 2026-06-26T00:00:00Z https://repositorio.fleni.org.ar/xmlui/handle/123456789/1619 Endovascular embolization of tentorial dural arteriovenous fistulas (EMBOTENT): a retrospective multicenter study Vollherbst, Dominik F.; Krug, Nadja; Zhang, Peng; Ma, Yongjie; Su, Xin; Limbucci, Nicola; Renieri, Leonardo; Mosimann, Pascal J.; Boutet, Alexandre; Cheng, How-Chung; Marnat, Gaultier; Barreau, Xavier; Szikora, Istvan; Czencz, Máté; González, Alejandro; Albóniga-Chindurza, Asier de; Scarcia, Luca; Kalsoum, Erwah; Alexandre, Andrea M.; Pujol Lereis, Virginia Andrea Background: Tentorial dural arteriovenous fistulas (TDAVFs) are rare but high risk vascular lesions. Although endovascular embolization is often the preferred treatment, large scale data on efficacy and safety are limited. Objective: To investigate the efficacy and safety of endovascular treatment for TDAVFs in a large, retrospective, multicenter cohort, and to analyze lesion characteristics and outcomes according to TDAVF location. Methods: Clinical, radiological, and interventional data from 585 patients treated in 32 international centers in 758 endovascular treatment sessions between 2012 and 2022 were analyzed. Patient demographics, fistula characteristics, endovascular treatment techniques, complications, and outcomes were assessed. Efficacy was measured by occlusion rates, safety by symptomatic complications, and modified Rankin Scale (mRS) scores. Results: In 31.3% of cases TDAVFs initially presented with hemorrhage, including 12.8% in low grade TDAVFs (absence of cortical venous reflux). Transarterial embolization was the primary approach in 84.7% of sessions. Complete occlusion was achieved in 74.2% of cases after the last treatment and 85.7% at the last imaging follow-up (mean 20.9 months). Symptomatic complications occurred in 9.4% of patients, with 2.6% permanent deficits and 1.0% mortality. At the last clinical follow-up (mean 30.6 months), 89.2% of patients had good functional outcome (mRS score 0-2). Location was significantly associated with fistula grade (eg, galenic and tentorial sinus TDAVFs being more often high grade, and torcular TDAVFs being more often low-grade). Conclusions: This large multicenter series demonstrated high occlusion rates, favorable functional outcomes, and acceptable complication rates, supporting endovascular therapy as a treatment of choice for TDAVFs. Considerable hemorrhage rates in low grade TDAVFs support the treatment even in the absence of cortical venous reflux. 2026-05-04T00:00:00Z https://repositorio.fleni.org.ar/xmlui/handle/123456789/1618 Generation of a human induced pluripotent stem cell line (FLENIi004-A) from an Autosomal-Dominant Alzheimer's disease PSEN1 p.M146L patient Vautier, Mercedes Florencia; Chrem Méndez, Patricio Alexis; Jerez Ferreyra, Guillermo; Massazza, Victoria; Apecetche, Manuela; Rodríguez Varela, María Soledad; Clas, Giulia Solange; Nievas, Micaela; Allegri, Ricardo Francisco; Sevlever, Gustavo Emilio; Scassa, María Élida; Surace, Ezequiel Ignacio; Marazita, Mariela Claudia; Romorini, Leonardo Human induced pluripotent stem cell (hiPSC) line FLENIi004-A was generated from peripheral blood mononuclear cells (PBMCs) using the lentiviral-hSTEMCCA-loxP vector. FLENIi004-A was derived from a 41-year-old Argentinean Caucasian male patient with Autosomal-Dominant Alzheimer's Disease, who carried the heterozygous PSEN1 p.M146L mutation. The hiPSC line retained the PSEN1 mutation, and its pluripotency and trilineage differentiation potential were confirmed. 2026-06-01T00:00:00Z