https://repositorio.fleni.org.ar/xmlui/handle/123456789/807 Mon, 05 Oct 2026 15:19:20 GMT 2026-10-05T15:19:20Z https://repositorio.fleni.org.ar/xmlui/handle/123456789/1610 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. Fri, 19 Jun 2026 00:00:00 GMT https://repositorio.fleni.org.ar/xmlui/handle/123456789/1610 2026-06-19T00:00:00Z https://repositorio.fleni.org.ar/xmlui/handle/123456789/1609 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. Wed, 30 Sep 2026 00:00:00 GMT https://repositorio.fleni.org.ar/xmlui/handle/123456789/1609 2026-09-30T00:00:00Z https://repositorio.fleni.org.ar/xmlui/handle/123456789/1602 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. Thu, 23 Apr 2026 00:00:00 GMT https://repositorio.fleni.org.ar/xmlui/handle/123456789/1602 2026-04-23T00:00:00Z https://repositorio.fleni.org.ar/xmlui/handle/123456789/1600 Regression-based normative data for neuropsychological assessment in Buenos Aires, Argentina: RAVLT, trail making test, digit span, and verbal fluency Corvalán, Nicolás; Morello García, Florentina; Leiva, Samanta; Allegri, Ricardo Francisco; Crivelli, Lucía Objective: To develop regression-based normative data for a set of widely used neuropsychological tests and to provide a freely accessible normative data calculator for use in Buenos Aires, Argentina. Methods: Participants were drawn from a large clinical dataset and selected to reflect preserved global cognition, intact memory performance, and functional independence. Regression-based norms were developed for the Rey Auditory Verbal Learning Test, Verbal Fluency, Trail Making Test, and Digit Span tasks. For each model, predictors included age, sex, and years of education, as well as polynomial terms and interaction effects; final models were obtained via stepwise backward elimination procedures. Model assumptions were evaluated, and predictive performance was estimated using 10-fold cross-validation. Results: 393 participants met inclusion criteria. Age was negatively associated with verbal memory, fluency, and executive function, whereas higher educational attainment was associated with better performance. Women outperformed men in verbal memory and phonological fluency. Demographic variables explained between 2% and 23% of variance across tests. An open-access calculator was developed to facilitate individualized normative estimation in clinical settings. Conclusions: This study provides locally developed, regression-based norms for neuropsychological assessment in Buenos Aires – Argentina, addressing the lack of culturally relevant norms and limitations of traditional methods. Mon, 11 May 2026 00:00:00 GMT https://repositorio.fleni.org.ar/xmlui/handle/123456789/1600 2026-05-11T00:00:00Z