Ecological Assessment of Everyday Executive Functioning at Home and at School using the BRIEF Questionnaire following Childhood Traumatic Brain Injury (TBI)

IntroductionCognitive and behavioural aspects of executive functioning (EF) are frequently impaired following childhood TBI. The Behavior Rating Inventory of Executive Function (BRIEF) questionnaire provides an ecological assessment of EFs in everyday life in home and school environments. The aims of this study were to describe the dysexecutive disorders in children with TBI using the BRIEF; to compare parent- and teacher-ratings and to analyse the demographic and medical variables influencing outcome.MethodsParticipants: Children/adolescents aged 5–17 years 11 months, referred to a paediatric rehabilitation department following TBI. Outcome measures: the parent–and the teacher-report of the BRIEF were collected during neuropsychological assessment (2009–2014), as well as the teacher-report (from 2014). Age at injury and assessment, parental education and TBI severity were collected.Results194 patients (142 boys) participated in the study [mild (n=13), moderate (n=12) or severe (n=169: mean duration of coma 7.2 days; SD=6.5)]. 193 parent-reports and 28 complete teacher reports of the BRIEF were available. Mean age at injury/assessment were 6.9 (SD=4.4), and 11.8 (SD=3.5) years respectively. According to parent-ratings, children had significantly elevated scores in all BRIEF indices [Global Executive Composite (GEC), Behaviour Regulation Index (BRI), Metacognition Index (MI)], and subscales (mean T-scores 61–64; all P<.0001), with 24% to 48.0% scoring in the clinical range. Teachers’ ratings indicated similar deficits in all sub-scales (mean T-scores 63–70; all P<.001), with 39.3–57.2% scoring in the clinical range. For patients with teacher and parent-reports (n=27), no significant difference was found between parent and teacher ratings, which were significantly correlated (r: .44–.72). Regression analyses indicated that GEC was significantly predicted by older age at assessment. The regression model for BRI was not significant. For MI, younger age at injury and older age at assessment were significant predictors.Discussion and conclusionThis study highlights elevated levels of executive dysfunction in everyday life following childhood TBI, evident in home and school environments. Younger age at injury seems to influence the cognitive rather than the behavioural aspects of EFs, whereas older age at assessment is related to higher levels of complaints, probably due to the increasing levels of expectations

Keratinocyte Secretion of Cyclophilin B via the Constitutive Pathway Is Regulated through Its Cyclosporin-Binding Site

Cyclophilin B (CypB) is an endoplasmic reticulum (ER)-resident member of the cyclophilin family of proteins that bind cyclosporin A (CsA). We report that as in other cell types, CypB trafficked from the ER and was secreted by keratinocytes into the media in response to CsA. Concentrations as low as 1 p of CsA induced secretion of CypB. Using brefeldin A, we showed that CypB is secreted from keratinocytes via the constitutive secretory pathway. We defined that substitution of tryptophan residue 128 in the CsA-binding site of CypB with alanine resulted in dissociation of CypBW128A-green fluorescent protein (GFP) from the ER. Photobleaching studies revealed a significant reduction in the diffusible mobility of CypBW128A-GFP compared with CypBWT-GFP, consistent with redistribution of CypBW128A-GFP into secretory vesicles disconnected from the ER/Golgi network. Furthermore, CsA significantly decreased the mobility of CypBWT-GFP but not CypBW128A-GFP. These studies demonstrate that therapeutically relevant concentrations of CsA regulate secretion of CypB by keratinocytes, and that a key residue within the CsA-binding site of CypB controls retention of CypB within the ER and regulates entry into the secretory pathway. As keratinocytes express CypB receptors (CD147) and CypB exhibits chemotactic properties, these data have implications for the therapeutic effects of CsA in inflammatory skin disease

Primary structure and assignment to chromosome 6 of three related rat genes encoding liver serine protease inhibitors.

Three closely related SPI genes which encode highly homologous proteins of the serine protease inhibitor family secreted by rat liver (SPI-1, SPI-2 and SPI-3), were isolated from genomic libraries and sequenced, totally (SPI-2) or partially (SPI-1 and SPI-3). These genes all map on rat chromosome 6. Each of them spans about 10 kb and contains five exons separated by four introns, located at equivalent positions. S1 mapping analysis indicated that initiation of transcription occurs at the same position (tsp) in each of the three genes. In vitro transcription experiments demonstrated the presence of promoter elements upstream from the putative tsp. Detailed analysis of 5'-flanking sequences in the three SPI revealed major differences. A high degree of identity (70%) was found within a 350-bp region preceding the 'cap' site, with the exception of a 42-bp spacer, which was only found in SPI-3. Upstream from that point, SPI-1 and SPI-2 sequences remain largely homologous over at least 1 kb but completely diverge from the corresponding sequence in SPI-3. This may, at least partly, account for the differential regulation of the three SPI observed during acute inflammation and upon hypophysectomy.Journal ArticleResearch Support, Non-U.S. Gov'tSCOPUS: ar.jinfo:eu-repo/semantics/publishe