Challenges of the Effectiveness of Traumatic Brain Injuries Biomarkers in the Sports-Related Context

Traumatic brain injury affects 69 million people every year. One of the main limitations in managing TBI patients is the lack of univocal diagnostic criteria, including the absence of standardized assessment methods and guidelines. Computerized axial tomography is the first-choice examination, despite the limited prevalence of positivity; moreover, its performance is undesirable due to the risk of radiological exposure, prolonged stay in emergency departments, inefficient use of resources, high cost, and complexity. Furthermore, immediacy and accuracy in diagnosis and management of TBIs are critically unmet medical needs. Especially in the context of sports-associated TBI, there is a strong need for prognostic indicators to help diagnose and identify at-risk subjects to avoid their returning to play while the brain is still highly vulnerable. Fluid biomarkers may emerge as new prognostic indicators to develop more accurate prediction models, improving risk stratification and clinical decision making. This review describes the current understanding of the cellular sources, temporal profile, and potential utility of leading and emerging blood-based protein biomarkers of TBI; its focus is on biomarkers that could improve the management of mild TBI cases and can be measured readily and directly in the field, as in the case of sports-related contexts

LA VALUTAZIONE RADIOLOGICA DEL CARICO LESIONALE IN FASE SUBACUTA PREDICE IL RECUPERO FUNZIONALE NEL PAZIENTE CON ESITI DI TRAUMA CRANICO.

Abbiamo correlato il quadro radiologico con il quadro funzionale di ciascun paziente (30 soggetti affetti da trauma cranico), con l’obiettivo di testare il ruolo di queste scale come indice precoce del recupero funzionale

Selective visual neglect in right brain damaged patients with splenial interhemispheric disconnection

Left unilateral neglect is frequently reported after right hemispheric lesions of the middle cerebral artery (MCA) damaging the parietal-frontal cortical-subcortical network subserving space representation and awareness. However, accumulating evidence shows that neglect can also follow lesions of the posterior cerebral artery (PCA) that do not directly affect this parietal-frontal network. Surgical studies in the monkeys have demonstrated that complete callosal resection combined with lesion of the right optic tract entirely deprives the right hemisphere of visual inputs from the left hemispace provoking severe left unilateral neglect. Here, through the detailed study of two patients we show, for the first time, that PCA lesions selectively affecting the splenium of the corpus callosum and the adjacent right primary visual cortex provoke severe neglect selectively restricted to the visual domain. No trace of personal, motor or representational-imagery neglect was found. Also at variance with previous case studies in which neglect followed lesion of the trunk or the genu of the corpus callosum, no restriction of neglect to tasks performed with the right hand, no left hemispatial limb akinesia, no tactile extinction for the left hand and no tactile anomia for stimuli explored with the left hand were observed. These findings demonstrate that brain lesions depriving intact parietal and frontal attentional areas from specific sensory inputs can yield spatial neglect limited to specific sensory modalities or sectors of space

Ruolo dell'IGF-1 sul trofismo cerebrale in soggetti con esiti di trauma cranico severo

Si descrive una correlazione inversa tra valori sierici di IGF-1 ad un mese dall'evento e il grado di atrofia cerebrale a quattro mesi dall'event

Targeting Siderophore-Mediated Iron Uptake in <i>M. abscessus</i>: A New Strategy to Limit the Virulence of Non-Tuberculous Mycobacteria

Targeting pathogenic mechanisms, rather than essential processes, represents a very attractive approach for the development of new antimycobacterial drugs. In this context, iron acquisition routes have recently emerged as potentially druggable pathways. However, the importance of siderophore biosynthesis in the virulence and pathogenicity of M. abscessus (Mab) is still poorly understood. In this study, we investigated the Salicylate Synthase (SaS) of Mab as an innovative molecular target for the development of inhibitors of siderophore production. Notably, Mab-SaS does not have any counterpart in human cells, making it an interesting candidate for drug discovery. Starting from the analysis of the binding of a series of furan-based derivatives, previously identified by our group as inhibitors of MbtI from M. tuberculosis (Mtb), we successfully selected the lead compound 1, exhibiting a strong activity against Mab-SaS (IC50 ≈ 5 µM). Computational studies characterized the key interactions between 1 and the enzyme, highlighting the important roles of Y387, G421, and K207, the latter being one of the residues involved in the first step of the catalytic reaction. These results support the hypothesis that 5-phenylfuran-2-carboxylic acids are also a promising class of Mab-SaS inhibitors, paving the way for the optimization and rational design of more potent derivatives

Targeting Siderophore-Mediated Iron Uptake in M. abscessus: A New Strategy to Limit the Virulence of Non-Tuberculous Mycobacteria

Targeting pathogenic mechanisms, rather than essential processes, represents a very attractive approach for the development of new antimycobacterial drugs. In this context, iron acquisition routes have recently emerged as potentially druggable pathways. However, the importance of siderophore biosynthesis in the virulence and pathogenicity of M. abscessus (Mab) is still poorly understood. In this study, we investigated the Salicylate Synthase (SaS) of Mab as an innovative molecular target for the development of inhibitors of siderophore production. Notably, Mab-SaS does not have any counterpart in human cells, making it an interesting candidate for drug discovery. Starting from the analysis of the binding of a series of furan-based derivatives, previously identified by our group as inhibitors of MbtI from M. tuberculosis (Mtb), we successfully selected the lead compound 1, exhibiting a strong activity against Mab-SaS (IC50 &asymp; 5 &micro;M). Computational studies characterized the key interactions between 1 and the enzyme, highlighting the important roles of Y387, G421, and K207, the latter being one of the residues involved in the first step of the catalytic reaction. These results support the hypothesis that 5-phenylfuran-2-carboxylic acids are also a promising class of Mab-SaS inhibitors, paving the way for the optimization and rational design of more potent derivatives