Neonatal Apex Resection Triggers Cardiomyocyte Proliferation, Neovascularization and Functional Recovery Despite Local Fibrosis

So far, opposing outcomes have been reported following neonatal apex resection in mice, questioning the validity of this injury model to investigate regenerative mechanisms. We performed a systematic evaluation, up to 180 days after surgery, of the pathophysiological events activated upon apex resection. In response to cardiac injury, we observed increased cardiomyocyte proliferation in remote and apex regions, neovascularization, and local fibrosis. In adulthood, resected hearts remain consistently shorter and display permanent fibrotic tissue deposition in the center of the resection plane, indicating limited apex regrowth. However, thickening of the left ventricle wall, explained by an upsurge in cardiomyocyte proliferation during the initial response to injury, compensated cardiomyocyte loss and supported normal systolic function. Thus, apex resection triggers both regenerative and reparative mechanisms, endorsing this injury model for studies aimed at promoting cardiomyocyte proliferation and/or downplaying fibrosis. In this article, Nascimento and colleagues demonstrate that neonatal apex resection stimulates cardiomyocyte proliferation and permanent scarring in the apex. Newly formed cardiomyocytes compensate muscle loss by resection, and resected hearts recover functional competence in adulthood. These findings endorse this model for studies aiming to block cardiac fibrosis and/or favoring CM proliferation

Onasemnogene abeparvovec in spinal muscular atrophy: an Australian experience of safety and efficacy

First published: 16 February 2022Objective: To provide a greater understanding of the tolerability, safety and clinical outcomes of onasemnogene abeparvovec in real-world practice, in a broad population of infants with spinal muscular atrophy (SMA). Methods: A prospective cohort study of children with SMA treated with onasemnogene abeparvovec at Sydney Children's Hospital Network, Australia was conducted from August 2019 to November 2021. Safety outcomes included clinical and laboratory evaluations. Efficacy assessments included World Health Organisation (WHO) motor milestones, oral and swallowing abilities, and requirements for respiratory support. The implementation of a model of care for onasemnogene abeparvovec administration in health practice is described. Results: 21 children were treated (age range, 0.65–24 months; body weight range, 2.5–12.5 kg) and 19/21 (90.4%) had previous nusinersen. Transient treatment-related side effects occurred in all children; vomiting (100%), transaminitis (57%) and thrombocytopaenia (33%). Incidence of moderate/severe transaminitis was significantly greater in infants weighing ≥8 kg compared with <8 kg (p < 0.05). Duration of prednisolone following treatment was prolonged (mean 87.5 days, range 57–274 days). 16/21 (76%) children gained at least one WHO motor milestone. Stabilisation or improvement in bulbar or respiratory function was observed in 20/21 (95.2%) patients. Implementation challenges were mitigated by developing standard operating procedures and facilitating exchange of knowledge. Interpretation: This study provides real-world evidence to inform treatment decisions and guide therapeutic expectations for onasemnogene abeparvovec and combination therapy for SMA in health practice, especially for children weighing ≥8 kg receiving higher vector loads. Proactive clinical and laboratory surveillance is essential to facilitate individualised management of risks.Arlene M. D’Silva, Sandra Holland, Didu Kariyawasam, Karen Herbert, Peter Barclay, Anita Cairns, Suzanna C. MacLennan, Monique M. Ryan, Hugo Sampaio, Nicholas Smith, Ian R. Woodcock, Eppie M. Yiu, Ian E. Alexander and Michelle A. Farra

Percepção ambiental dos produtores e qualidade do solo em propriedades orgânicas e convencionais.

O sistema orgânico de produção deve resultar na utilização mais racional dos recursos naturais, sobretudo do solo. Os produtores orgânicos devem adotar práticas conservacionistas, além de atender a outros princípios deste sistema de produção. Neste trabalho foram avaliadas as práticas de manejo e conservação do solo adotadas por produtores orgânicos e convencionais nas regiões dos municípios de Socorro (Serra da Mantiqueira e Mogiana) e Ibiúna, situados no Estado de São Paulo. O objetivo dessa pesquisa foi verificar o grau de adoção de práticas conservacionistas pelos produtores e avaliar a qualidade do solo na agricultura orgânica e convencional. Foi elaborado e aplicado um questionário, com visitas locais para verificação das práticas conservacionistas e ocorrência de erosão, em 30 propriedades. Os resultados foram expressos em índices indicadores de diversidade de uso do solo, atitude conservacionista, percepção de erosão e do impacto sobre os recursos hídricos. Foram também realizadas análises de atributos químicos, físicos e biológicos indicadores da qualidade do solo. Concluiu-se que os produtores orgânicos têm maior percepção quanto à atitude conservacionista e nas propriedades orgânicas há maior diversidade de cultivos, embora não haja maior diversidade geral de uso do solo. A produção orgânica de alface, em Ibiúna proporcionou maior atividade biológica no solo e maior colonização por fungos micorrízicos arbusculares. O sistema orgânico possui maiores teores de matéria orgânica e menores de potássio e não houve diferença entre os atributos físicos do solo dos sistemas orgânico e convencional

Black Hole Remnants at the LHC

We investigate possible signatures of black hole events at the LHC in the hypothesis that such objects will not evaporate completely, but leave a stable remnant. For the purpose of defining a reference scenario, we have employed the publicly available Monte Carlo generator CHARYBDIS2, in which the remnant's behavior is mostly determined by kinematic constraints and conservation of some quantum numbers, such as the baryon charge. Our findings show that electrically neutral remnants are highly favored and a significantly larger amount of missing transverse momentum is to be expected with respect to the case of complete decay.Comment: LaTeX, 13 pages, 2 tables, 5 figures, references added and typos corrected. To appear in EPJ