https://repositorio.fleni.org.ar/xmlui/handle/123456789/809 2026-10-07T14:41:11Z 2026-10-07T14:41:11Z Vishnopolska, Sebastian Liu, James Camilletti, María Andrea Martínez Mayer, Julián Iglesias García, Lucía Brinkmeier, Michelle Vaiani, Elisa Vidal, Sofia Hebe Ciaccio, Marta Di Palma, María Isabel Belgorosky, Alicia Marti, Marcelo Hufnagel, Robert B. Camper, Sally A. Pérez-Millán, María Inés https://repositorio.fleni.org.ar/xmlui/handle/123456789/1610 2026-10-01T14:47:35Z 2026-06-19T00:00:00Z

Compound Heterozygous Variants in the Phospholipase Gene PNPLA6 Cause Hypopituitarism and Vision Loss Vishnopolska, Sebastian; Liu, James; Camilletti, María Andrea; Martínez Mayer, Julián; Iglesias García, Lucía; Brinkmeier, Michelle; Vaiani, Elisa; Vidal, Sofia Hebe; Ciaccio, Marta; Di Palma, María Isabel; Belgorosky, Alicia; Marti, Marcelo; Hufnagel, Robert B.; Camper, Sally A.; Pérez-Millán, María Inés NPLA6 is a conserved lysophospholipase essential for maintaining nervous system integrity. Biallelic mutations in PNPLA6 have been identified in individuals with a broad spectrum of disorders that can include ataxia, vision loss, and pituitary hormone deficiency. Here, we report the identification of novel compound heterozygous variants in PNPLA6 (p.T1115P and p.Pro1142_Ala1143ins14) in a 10-year-old girl with combined pituitary hormone deficiency, including growth hormone, thyroid-stimulating hormone, and gonadotropins. She also has vision loss and neurodevelopmental delay. Functional validation demonstrates that both variants, a missense substitution affecting a highly conserved residue within the catalytic domain and an intronic variant generating a novel splice acceptor site, completely abolish NTE activity, establishing their pathogenicity. Little is known about the cause of hypopituitarism in individuals with PNPLA6 deficiency. Here, we report the cell-type-specific expression of PNPLA6 in mouse pituitary development and in adult animals. PNPLA6 is expressed broadly in SOX2+ stem cells within the pituitary primordium as early as e10.5, prior to lineage specification, suggesting a role in progenitor maintenance and early differentiation. In neonates and adults, expression predominates in the cells that produce growth hormone and pro-opiomelanocortin. These findings suggest that PNPLA6 could influence pituitary development at early stages, as well as contribute to the altered function of hormone-secreting cells.

2026-06-19T00:00:00Z Testa, Nelly Pochetti, Juliana Russo, María Julieta https://repositorio.fleni.org.ar/xmlui/handle/123456789/1609 2026-10-01T12:18:53Z 2026-09-30T00:00:00Z

Assessment of sports-related concussion in children and adolescents Testa, Nelly; Pochetti, Juliana; Russo, María Julieta Advances in research on sports-related concussions have led to updates in diagnostic and management protocols. This article reviews the recommendations from the Sixth International Consensus Conference on Concussion in Sport (Amsterdam, 2022), focusing on children (ages 8-12) and adolescents (ages 13-18). It highlights preventive strategies, such as identifying risk factors, using protective equipment, implementing regulatory changes, and engaging in neuromuscular training. Up-to-date clinical tools are recommended for identification and monitoring. Initial management includes relative rest for 24-48 hours, with limited screen time, followed by subthreshold physical exercise. Specific rehabilitation is indicated if symptoms persist. This comprehensive, evidence-based approach optimizes recovery and minimizes long-term effects, promoting the safety and well-being of young athletes.The proposed protocol aims to guide pediatricians and sports professionals in clinical decision-making.

2026-09-30T00:00:00Z Jiménez, Daniel A. Bagnati, Pablo M. Flores Montes, Rosa Elena Fernández, María Laura Zuno Reyes, Angélica Aguillón, David Aláez Versón, Carmen Becerra Solano, Luis Eduardo Behrens, María Isabel Branda, Kelly Chrem Méndez, Patricio Alexis Custodio, Nilton Ducaine, Whitney Dumois Petersen, Sofía Figuera, Luis Londoño Castaño, Marisol Longoria, Erika Mariana Matute, Esmeralda Surace, Ezequiel Ignacio Programa de asesoramiento genético en América Latina (PRAGA) https://repositorio.fleni.org.ar/xmlui/handle/123456789/1605 2026-10-05T16:07:19Z 2026-05-27T00:00:00Z

Recommendations for genetic counseling for individuals at risk of autosomal dominant Alzheimer's disease in Latin America Jiménez, Daniel A.; Bagnati, Pablo M.; Flores Montes, Rosa Elena; Fernández, María Laura; Zuno Reyes, Angélica; Aguillón, David; Aláez Versón, Carmen; Becerra Solano, Luis Eduardo; Behrens, María Isabel; Branda, Kelly; Chrem Méndez, Patricio Alexis; Custodio, Nilton; Ducaine, Whitney; Dumois Petersen, Sofía; Figuera, Luis; Londoño Castaño, Marisol; Longoria, Erika Mariana; Matute, Esmeralda; Surace, Ezequiel Ignacio; Programa de asesoramiento genético en América Latina (PRAGA) Autosomal dominant Alzheimer's disease (ADAD) represents a small but impactful subset of Alzheimer's cases. Asymptomatic individuals at genetic risk face substantial personal and family implications when considering predictive testing for known familial variants. Genetic counseling and testing (GCT) frameworks remain limited in Latin America (LatAm). Recommendations for GCT in LatAm were developed through an iterative, multidisciplinary consensus process. Evidence inputs included a structured literature review, site‐level recommendations from participating LatAm centers, and a qualitative synthesis of focus groups with experienced investigators. The resulting model includes pre‐test evaluation, sample collection, result disclosure, and structured follow‐up. Core elements comprise mental health assessment, psychoeducation, exploration of expectations and decision‐making needs, guided disclosure with emotional support, and a suggested 3‐month post‐disclosure reassessment using validated psychological measures. Our framework provides structured guidance for the safe and ethical delivery of GCT for ADAD through a multidisciplinary, culturally informed, and patient‐centered approach in LatAm.

2026-05-27T00:00:00Z Freiberger, Rosa Nicole López, Cynthia Alicia Marcela Palma, María Belén Cevallos, Cintia Sviercz, Franco Agustin Jarmoluk, Patricio García, Marcela Nilda Quarleri, Jorge Delpino, María Victoria https://repositorio.fleni.org.ar/xmlui/handle/123456789/1602 2026-09-30T18:11:24Z 2026-04-23T00:00:00Z

Brucella abortus Infection Promotes Mesenchymal Stem Cell Differentiation Toward Adipogenesis, Enhancing the Proinflammatory Profile Freiberger, Rosa Nicole; López, Cynthia Alicia Marcela; Palma, María Belén; Cevallos, Cintia; Sviercz, Franco Agustin; Jarmoluk, Patricio; García, Marcela Nilda; Quarleri, Jorge; Delpino, María Victoria The most common complication of active brucellosis in humans is osteoarticular injury. In the bone marrow microenvironment, mesenchymal stem cells (MSCs) can differentiate into either adipocytes or osteoblasts, and this balance is tightly regulated because an increase in adipogenesis may negatively affect bone formation and favor bone loss. The differentiation of MSCs into adipocytes or osteoblasts is tightly regulated by mechanisms that promote cell fate toward one lineage while repressing the other. Our study demonstrated that Brucella abortus infects MSCs but does not affect the deposition of organic and mineral matrix during osteoblast differentiation. However, the infection upregulates Receptor Activator of Nuclear Factor Kappa-B Ligand (RANKL) expression in osteoblasts, which may contribute to osteoclast activation and bone resorption. Conversely, B. abortus infection significantly influences adipocyte differentiation by modulating lipolysis, lipogenesis, and interactions between lipid droplets and mitochondria. This leads to increased cellular cholesterol levels and reduced intracellular triglycerides, accompanied by glycerol release. These changes result in more differentiated adipocytes and larger lipid droplets. Consequently, we observed increased IL-6 secretion and a higher leptin/adiponectin ratio. Importantly, these effects were independent of a functional type IV secretion system (T4SS), as purified Brucella DNA fully reproduced the adipogenic phenotype. Moreover, inhibition of TLR9—the primary sensor of bacterial DNA—significantly reduced the DNA-induced adipogenic response, demonstrating that adipocyte modulation is at least in part mediated through TLR9 signaling. In summary, B. abortus promotes MSC differentiation toward an inflammatory adipocyte phenotype. It involves a TLR-9-mediated DNA detection. It may contribute to osteoarticular injury and infection-associated bone resorption.

2026-04-23T00:00:00Z