Specific nanoprobe design for MRI: Targeting laminin in the blood-brain barrier to follow alteration due to neuroinflammation

by Juan F. Zapata-Acevedo, Mónica Losada-Barragán, Johann F. Osma, Juan C. Cruz, Andreas Reiber, Klaus G. Petry, Amael Caillard, Audrey Sauldubois, Daniel Llamosa Pérez, Aníbal José Morillo Zárate, Sonia Bermúdez Muñoz, Agustín Daza Moreno, Rafaela V. Silva, Carmen Infante-Duarte, William Chamorro-Coral, Rodrigo E. González-Reyes, Karina Vargas-Sánchez

Chronic neuroinflammation is characterized by increased blood-brain barrier (BBB) permeability, leading to molecular changes in the central nervous system that can be explored with biomarkers of active neuroinflammatory processes. Magnetic resonance imaging (MRI) has contributed to detecting lesions and permeability of the BBB. Ultra-small superparamagnetic particles of iron oxide (USPIO) are used as contrast agents to improve MRI observations. Therefore, we validate the interaction of peptide-88 with laminin, vectorized on USPIO, to explore BBB molecular alterations occurring during neuroinflammation as a potential tool for use in MRI. The specific labeling of NPS-P88 was verified in endothelial cells (hCMEC/D3) and astrocytes (T98G) under inflammation induced by interleukin 1β (IL-1β) for 3 and 24 hours. IL-1β for 3 hours in hCMEC/D3 cells increased their co-localization with NPS-P88, compared with controls. At 24 hours, no significant differences were observed between groups. In T98G cells, NPS-P88 showed similar nonspecific labeling among treatments. These results indicate that NPS-P88 has a higher affinity towards brain endothelial cells than astrocytes under inflammation. This affinity decreases over time with reduced laminin expression. In vivo results suggest that following a 30-minute post-injection, there is an increased presence of NPS-P88 in the blood and brain, diminishing over time. Lastly, EAE animals displayed a significant accumulation of NPS-P88 in MRI, primarily in the cortex, attributed to inflammation and disruption of the BBB. Altogether, these results revealed NPS-P88 as a biomarker to evaluate changes in the BBB due to neuroinflammation by MRI in biological models targeting laminin.

Effects of tactical dimension and situational variables in throw-ins on the offensive performance in football

by Claudio A. Casal, Vasilis Armatas, José Luis Losada, Michalis Mitrotasios

The aim of the study was to describe the usual practices in the execution of throw-ins by La Liga teams during the 2021–2022 season, identify tactical indicators related to the outcome of plays that start with a throw-in, calculate their predictive power, and finally analyse the influence of situational variables on the effectiveness of these plays. A total of 2,658 throw-ins, during 80 matches were analysed. Two UEFA PRO coaches designed an ad hoc observation instrument “Thrinfoot” and two observers coded the data after a training process. Inter and intra-observer reliability was calculated using Cohen´s Kappa coefficient, revealing almost perfect agreement. Multinomial logistic regression was applied to predict the throw-ins outcome (p2 (OR = 4.1, p