Trait anxiety: a hidden variable in physiological and pathological processes

Nell\u2019uomo esiste una differenza nella risposta agli stimoli stressogeni, che dipende dalla personale predisposizione all\u2019ansia, detta specificatamente \u201ctratto d\u2019ansia\u201d. La differente suscettibilit\ue0 all\u2019ansia \ue8 stata studiata nei roditori creando ceppi selezionati per tratti di elevata e bassa ansia; inoltre \ue8 stato dimostrato, sia nell\u2019uomo che nei ceppi selezionati di roditori, che differenti livelli di ansia basale influenzano la capacit\ue0 dei soggetti di attuare un determinato compito, anche cognitivo. Tuttavia la suscettibilit\ue0 individuale, all\u2019interno di uno stesso ceppo di ratti na\uefve, \ue8 ancora poco studiata. Lo scopo di questo studio quindi \ue8 stato quello di valutare le possibili differenze interindividuali nel livello d\u2019ansia, all\u2019interno di una popolazione di ratti appartenenti al ceppo Wistar, e di fornire indicazioni su come uno specifico tratto d\u2019ansia possa influenzare una successiva performance cognitiva, valutata mediante un test cognitivo ampiamente utilizzato, il Novel Object Recognition (NOR) test. Seguendo questa linea di ricerca poi, abbiamo voluto indagare se il tratto di ansia potesse influenzare la suscettibilit\ue0 del ceppo di topo C57Bl/6J all\u2019insorgenza dell\u2019 epilessia, e se l\u2019esposizione ad un fattore fortemente stressogeno per il topo, l\u2019odore di un suo predatore, potesse provocare un aggravamento della malattia durante la fase cronica. Questo lavoro di tesi mostra come esista una variabilit\ue0 interindividuale all\u2019interno di una popolazione di roditori per quanto riguarda l\u2019ansia di tratto, cio\ue8 la componente basale di ansia insita in ogni individuo. Questo fattore pu\uf2 influenzare la risposta ad alcuni compiti a cui l\u2019animale deve rispondere, come ad esempio quelli cognitivi. Il tratto d\u2019ansia basale potrebbe anche influenzare la predisposizione all\u2019insorgenza di una determinata malattia, oppure il decorso della malattia stessa. E\u2019 perci\uf2 molto importante considerare il tratto d\u2019ansia basale di ciascun soggetto sperimentale in tutti gli studi che prevedano una componente comportamentale, includendo tale dato come fattore covariato nelle analisi statistiche, cos\uec da evitare errori dovuti a questa variabile nascosta.Human subjects display a great variability in the predisposition to respond anxiogenically to stimuli, i.e. trait anxiety. This susceptibility has been studied in rodents through the creation of selected strains for anxiety-like behaviour, to obtain extreme anxiety traits. Moreover, anxiety has been shown to variously affect physiological processes, such as a cognitive task performance, both in humans and selected rodents strains. However, interindividual differences in basal anxiety level in na\uefve rats and how they may affect cognitive functioning have been poorly investigated. Therefore, the aim of this study is to provide an evidence of the huge interindividual differences in anxiety levels in a population of na\uefve Wistar rats and demonstrate how they can affect a widely used cognitive test, the Novel Object Recognition (NOR) test. Following this line of research, in this study we also investigate if trait anxiety could affect pathological processes, such as the susceptibility on the onset of a neurological disease, the temporal lobe epilepsy, in a population of C57Bl/6J mice. Finally, we evaluate if the exposure to a strong stressful factor for mice, such as a predator odor, could induce an increase of the pathological process in chronic phase of the illness, for example in the number of seizures, in the same epileptic animals. These results could show the relevance to consider trait anxiety, the propension to response in a manner more or less anxious to a specific stimulus, of each subject, in order to avoid interpretative errors during the evaluation of a specific behaviour shown by the subject. Therefore we claim the need to consider interindividual differences in emotionality (e.g. anxiety) in general, and the need to assess anxiety level while studying rats cognitive abilities. It will be possible to include it as a covariate in the statistical analysis, in studies that schedule behavioural factors, in order to avoid interpretative errors dued to this hidden variable

Prognostic Value of Thrombus Volume and Interaction With First-Line Endovascular Treatment Device Choice

BACKGROUND: A larger thrombus in patients with acute ischemic stroke might result in more complex endovascular treatment procedures, resulting in poorer patient outcomes. Current evidence on thrombus volume and length related to procedural and functional outcomes remains contradicting. This study aimed to assess the prognostic value of thrombus volume and thrombus length and whether this relationship differs between first-line stent retrievers and aspiration devices for endovascular treatment.METHODS: In this multicenter retrospective cohort study, 670 of 3279 patients from the MR CLEAN Registry (Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands) for endovascularly treated large vessel occlusions were included. Thrombus volume (0.1 mL) and length (0.1 mm) based on manual segmentations and measurements were related to reperfusion grade (expanded Treatment in Cerebral Infarction score) after endovascular treatment, the number of retrieval attempts, symptomatic intracranial hemorrhage, and a shift for functional outcome at 90 days measured with the reverted ordinal modified Rankin Scale (odds ratio &gt;1 implies a favorable outcome). Univariable and multivariable linear and logistic regression were used to report common odds ratios (cORs)/adjusted cOR and regression coefficients (B/aB) with 95% CIs. Furthermore, a multiplicative interaction term was used to analyze the relationship between first-line device choice, stent retrievers versus aspiration device, thrombus volume, and outcomes.RESULTS: Thrombus volume was associated with functional outcome (adjusted cOR, 0.83 [95% CI, 0.71-0.97]) and number of retrieval attempts (aB, 0.16 [95% CI, 0.16-0.28]) but not with the other outcome measures. Thrombus length was only associated with functional independence (adjusted cOR, 0.45 [95% CI, 0.24-0.85]). Patients with more voluminous thrombi had worse functional outcomes if endovascular treatment was based on first-line stent retrievers (interaction cOR, 0.67 [95% CI, 0.50-0.89]; P=0.005; adjusted cOR, 0.74 [95% CI, 0.55-1.0]; P=0.04). CONCLUSIONS: In this study, patients with a more voluminous thrombus required more endovascular thrombus retrieval attempts and had a worse functional outcome. Patients with a lengthier thrombus were less likely to achieve functional independence at 90 days. For more voluminous thrombi, first-line stent retrieval compared with first-line aspiration might be associated with worse functional outcome.</p

Prognostic Value of Thrombus Volume and Interaction With First-Line Endovascular Treatment Device Choice

Background: A larger thrombus in patients with acute ischemic stroke might result in more complex endovascular treatment procedures, resulting in poorer patient outcomes. Current evidence on thrombus volume and length related to procedural and functional outcomes remains contradicting. This study aimed to assess the prognostic value of thrombus volume and thrombus length and whether this relationship differs between first-line stent retrievers and aspiration devices for endovascular treatment. Methods: In this multicenter retrospective cohort study, 670 of 3279 patients from the MR CLEAN Registry (Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands) for endovascularly treated large vessel occlusions were included. Thrombus volume (0.1 mL) and length (0.1 mm) based on manual segmentations and measurements were related to reperfusion grade (expanded Treatment in Cerebral Infarction score) after endovascular treatment, the number of retrieval attempts, symptomatic intracranial hemorrhage, and a shift for functional outcome at 90 days measured with the reverted ordinal modified Rankin Scale (odds ratio >1 implies a favorable outcome). Univariable and multivariable linear and logistic regression were used to report common odds ratios (cORs)/adjusted cOR and regression coefficients (B/aB) with 95% CIs. Furthermore, a multiplicative interaction term was used to analyze the relationship between first-line device choice, stent retrievers versus aspiration device, thrombus volume, and outcomes. Results: Thrombus volume was associated with functional outcome (adjusted cOR, 0.83 [95% CI, 0.71-0.97]) and number of retrieval attempts (aB, 0.16 [95% CI, 0.16-0.28]) but not with the other outcome measures. Thrombus length was only associated with functional independence (adjusted cOR, 0.45 [95% CI, 0.24-0.85]). Patients with more voluminous thrombi had worse functional outcomes if endovascular treatment was based on first-line stent retrievers (interaction cOR, 0.67 [95% CI, 0.50-0.89]; P=0.005; adjusted cOR, 0.74 [95% CI, 0.55-1.0]; P=0.04). Conclusions: In this study, patients with a more voluminous thrombus required more endovascular thrombus retrieval attempts and had a worse functional outcome. Patients with a lengthier thrombus were less likely to achieve functional independence at 90 days. For more voluminous thrombi, first-line stent retrieval compared with first-line aspiration might be associated with worse functional outcome