Genetic redox dysregulation induces behavioural deficits in the adult mouse: an animal model for schizophrenia

Background: Glutathione (GSH), a major cellular redox regulator and antioxidant, is decreased in cerebrospinal fluid and prefrontal cortex of schizophrenia patients. The gene of the key GSH-synthesizing enzyme, glutamate-cysteine ligase, modifier (GCLM) subunit, is associated with schizophrenia, suggesting that the deficit in the GSH system is of genetic origin. Using the GCLM knock-out (KO) mouse as model system with 60% decreased brain GSH levels and, thus, strong vulnerability to oxidative stress, we have shown that GSH dysregulation results in abnormal mouse brain morphology (e.g., reduced parvalbumin, PV, immuno-reactivity in frontal areas) and function. Additional oxidative stress, induced by GBR12909 (a dopamine re-uptake inhibitor), enhances morphological changes even further. Aim: In the present study we use the GCLM KO mouse model system, asking now, whether GSH dysregulation also compromises mouse behaviour and cognition. Methods: Male and female wildtype (WT) and GCLM-KO mice are treated with GBR12909 or phosphate buffered saline (PBS) from postnatal day (P) 5 to 10, and are behaviourally tested at P 60 and older. Results: In comparison to WT, KO animals of both sexes are hyperactive in the open field, display more frequent open arm entries on the elevated plus maze, longer float latencies in the Porsolt swim test, and more frequent contacts of novel and familiar objects. Contrary to other reports of animal models with reduced PV immuno-reactivity, GCLM-KO mice display normal rule learning capacity and perform normally on a spatial recognition task. GCLM-KO mice do, however, show a strong deficit in object-recognition after a 15 minutes retention delay. GBR12909 treatment exerts no additional effect. Conclusions: The results suggest that animals with impaired regulation of brain oxidative stress are impulsive and have reduced behavioural control in novel, unpredictable contexts. Moreover, GSH dysregulation seems to induce a selective attentional or stimulus-encoding deficit: despite intensive object exploration, GCLM-KO mice cannot discriminate between novel and familiar objects. In conclusion, the present data indicate that GSH dysregulation may contribute to the manifestation of behavioural and cognitive anomalies that are associated with schizophrenia.

Improved accuracy of co-morbidity coding over time after the introduction of ICD-10 administrative data.

BACKGROUND: Co-morbidity information derived from administrative data needs to be validated to allow its regular use. We assessed evolution in the accuracy of coding for Charlson and Elixhauser co-morbidities at three time points over a 5-year period, following the introduction of the International Classification of Diseases, 10th Revision (ICD-10), coding of hospital discharges.METHODS: Cross-sectional time trend evaluation study of coding accuracy using hospital chart data of 3'499 randomly selected patients who were discharged in 1999, 2001 and 2003, from two teaching and one non-teaching hospital in Switzerland. We measured sensitivity, positive predictive and Kappa values for agreement between administrative data coded with ICD-10 and chart data as the 'reference standard' for recording 36 co-morbidities.RESULTS: For the 17 the Charlson co-morbidities, the sensitivity - median (min-max) - was 36.5% (17.4-64.1) in 1999, 42.5% (22.2-64.6) in 2001 and 42.8% (8.4-75.6) in 2003. For the 29 Elixhauser co-morbidities, the sensitivity was 34.2% (1.9-64.1) in 1999, 38.6% (10.5-66.5) in 2001 and 41.6% (5.1-76.5) in 2003. Between 1999 and 2003, sensitivity estimates increased for 30 co-morbidities and decreased for 6 co-morbidities. The increase in sensitivities was statistically significant for six conditions and the decrease significant for one. Kappa values were increased for 29 co-morbidities and decreased for seven.CONCLUSIONS: Accuracy of administrative data in recording clinical conditions improved slightly between 1999 and 2003. These findings are of relevance to all jurisdictions introducing new coding systems, because they demonstrate a phenomenon of improved administrative data accuracy that may relate to a coding 'learning curve' with the new coding system.

Oeuvres complètes de Tabarin : avec les Rencontres, fantaisies et coq-à-l'âne facétieux du baron de Gratelard , et divers opuscules publiés séparément sous le nom ou à propos de Tabarin. Tome 1 / Le tout précédé d'une introduction et d'une bibliographie tabarinique par Gustave Aventin

Collection : Bibliothèque elzévirienne ; 65, 1-2

Oeuvres complètes de Tabarin : avec les Rencontres, fantaisies et coq-à-l'âne facétieux du baron de Gratelard , et divers opuscules publiés séparément sous le nom ou à propos de Tabarin. Tome 2 / Le tout précédé d'une introduction et d'une bibliographie tabarinique par Gustave Aventin

Collection : Bibliothèque elzévirienne ; 65, 1-2

Oeuvres complètes de Tabarin : avec les Rencontres, fantaisies et coq-à-l'âne facétieux du baron de Gratelard , et divers opuscules publiés séparément sous le nom ou à propos de Tabarin. Tome 2 / Le tout précédé d'une introduction et d'une bibliographie tabarinique par Gustave Aventin

Collection : Bibliothèque elzévirienne ; 65, 1-2

Oeuvres complètes de Tabarin : avec les Rencontres, fantaisies et coq-à-l'âne facétieux du baron de Gratelard , et divers opuscules publiés séparément sous le nom ou à propos de Tabarin. Tome 1 / Le tout précédé d'une introduction et d'une bibliographie tabarinique par Gustave Aventin

Collection : Bibliothèque elzévirienne ; 65, 1-2

Le mystère de la Passion / d'Arnoul Greban ; publié d'après les manuscrits de Paris, avec une introduction et un glossaire, par Gaston Paris et Gaston Raynaud

[Mystère de la Passion (français moyen). 1878]