Progressive Early Breakdown of Retinal Pigment Epithelium Function in Hyperglycemic Rats.

PURPOSE: Diabetic macular edema (DME), an accumulation of fluid in the subretinal space, is a significant cause of vision loss. The impact of diabetes on the breakdown of the inner blood-retina barrier (BRB) is an established event that leads to DME. However, the role of the outer BRB in ocular diabetes has received limited attention. We present evidence that the breakdown of normal RPE function in hyperglycemia facilitates conditions conducive to DME pathogenesis. METHODS: Brown Norway rats (130-150 g) were injected intraperitoneally with streptozotocin (STZ; 60 mg/kg) to induce hyperglycemia. After 4 weeks, Evans blue (EB) dye was injected intravenously to determine whether there was leakage of albumin into the retina. Subretinal saline blebs (0.5-1 µL) were placed 4 and 9 weeks after STZ injection, and time-lapse optical coherence tomography tracked the resorption rate. In a subset of rats, intravitreal bevacizumab, a humanized monoclonal antibody targeted to VEGF, was given at 5 weeks and resorption was measured at 9 weeks. RESULTS: The ability of the RPE to transport fluid was reduced significantly after 4 and 9 weeks of hyperglycemia with a reduction of over 67% at 9 weeks. No EB dye leakage from inner retinal vessels was measured in hyperglycemic animals compared to control. The intravitreal administration of bevacizumab at week 5 significantly increased the rate of fluid transport in rats subjected to hyperglycemia for 9 weeks. CONCLUSIONS: These results demonstrate that chronic hyperglycemia altered RPE fluid transport, in part dependent on the actions of VEGF. These results support the idea that RPE dysfunction is an early event associated with hyperglycemia that contributes to fluid accumulation in DME.

Postconcussion syndrome (PCS) in the emergency department: predicting and pre-empting persistent symptoms following a mild traumatic brain injury.

Head injuries across all age groups represent an extremely common emergency department (ED) presentation. The main focus of initial assessment and management rightly concentrates on the need to exclude significant pathology, that may or may not require neurosurgical intervention. Relatively little focus, however, is given to the potential for development of post-concussion syndrome (PCS), a constellation of symptoms of varying severity, which may bear little correlation to the nature or magnitude of the precipitating insult. This review aims to clarify the aetiology and terminology surrounding PCS and to examine the mechanisms for diagnosing and treating.

Measurement Issues: Neuropsychological assessment with children and adolescents; unlocking the mysticism, methods and measures with the help of Tom Swift.

BACKGROUND AND SCOPE: In this article, we provide a brief overview of the principles that guide paediatric neuropsychological assessment, the methods used and some examples of the measures available. FINDINGS: We explore intellectual, adaptive and social functioning from a neuropsychological perspective and describe suitable measures for use in paediatric neuropsychological assessment in each domain. CONCLUSIONS: We provide an example of assessment and interpretation using a fictional character (Tom Swift) to demonstrate that neuropsychological assessment is important in understanding the everyday questions that arise in children's services around risk, needs, level of understanding and capacity to engage with services.

'Trails B or not Trails B?' Is attention-switching a useful outcome measure?

PRIMARY OBJECTIVE: Difficulties with attention contribute to behavioural and cognitive problems during childhood and may reflect subtle deficits in executive functioning (EF). Attention problems in early childhood have also been found to predict higher levels of anxiety and depression symptoms at 10 years old. It has also been reported that attention problems during childhood may be differentially related to later-emerging distinct EF difficulties. Many of these findings, however, rely on teacher-ratings of attention difficulties. METHODS AND PROCEDURES: This study administered neuropsychological tests of attention-switching and EF to 67 healthy children aged 9-15 years of age. It additionally measured socio-emotional behavioural functioning. MAIN OUTCOMES AND RESULTS: A critical phase of improvement was found at 10 years of age. Correlations were found between attention-switching skills and EF. Attention-switching skills were also correlated with socio-emotional functioning. CONCLUSIONS: Attention-switching skills have some interdependence with EF, but in paediatric assessment such skills are easier to routinely assess than many of the currently available tests of EF. It is suggested that attention-switching ability may prove to be a useful predictor of EF performance in understanding long-term outcome after a neurological event such as traumatic brain injury.

Resilience and the mediating effects of executive dysfunction after childhood brain injury: a comparison between children aged 9-15 years with brain injury and non-injured controls.

PRIMARY OBJECTIVE: Acquired brain injury (ABI) during childhood can be associated with enduring difficulties related to impairments to executive functioning (EF). EF impairments may detrimentally affect outcome by restricting an individual's ability to access 'resiliency' resources after ABI. RESEARCH DESIGN: The purpose of this study was to explore whether there is deterioration in children's resilience compared with peers after ABI and whether EF is influential in mediating relationships between resilience and behaviour. METHODS AND PROCEDURES: Measures of resilience, depression and anxiety were administered with 21 children with ABI and 70 matched healthy children aged 9-15 years. Parents completed measures of behaviour and EF. MAIN OUTCOMES AND RESULTS: Children with ABI were identified as less resilient and more depressed and anxious than controls. Resiliency measures were correlated with depression and anxiety in both groups. Relationships between resiliency and socio-emotional behaviour were mediated by EF. CONCLUSIONS: Assessment of resilience after ABI may be useful in supporting or defining the delivery of more individualized rehabilitation programmes according to the resources and vulnerabilities a young person has. However, an accurate understanding of the role of EF in the relationship between resilience and behavioural outcome after ABI is essential.

Cognitive correlates of psychosocial outcome following traumatic brain injury in early childhood: comparisons between groups of children aged under and over 10 years of age.

Children with traumatic brain injuries (TBI) commonly present with socioemotional difficulties, as well as accompanying multiple cognitive impairments. Often difficulties worsen at around 10 years old. This change is associated with frontal system changes, and tests of executive function (EF) predict outcome. However, children with TBI sometimes present with socioemotional difficulties despite apparent cognitive recovery. Our aims were to explore potential cognitive and socioemotional effects following childhood TBI, before and after the age of 10 years. We also wanted to identify cognitive correlates of psychosocial dysfunction. Measures of cognitive function and socioemotional disturbance administered to 14 children with TBI aged 8-10 years, and 14 children with TBI aged 10-16 years, were compared to control data from 22 non-injured 8- to 10 year-olds and 67 non-injured 10- to 16-year-olds. Results indicated that only the older group of children with TBI were impaired in tests of EF, but significant socioemotional difficulties were commonly evident in both groups. Processing speed (as well as EF) was found to correlate with socioemotional disturbance. We conclude that poor processing speed may also index the risk of socioemotional difficulties, but our general findings indicate that cognitive functions relevant to socioemotional functioning are not readily testable in younger children and are not strongly associated with such outcomes as they may be in adults.

Peer-relationship difficulties in children with brain injuries: comparisons with children in mental health services and healthy controls.

Positive peer relationships are essential in healthy development. The prevalence of peer-relationship problems in children after acquired brain injury (ABI) has yet to be explored, although ABI does inevitably impact upon peer interactions. We aimed to explore how peer-relationships and emotional distress after ABI may differ from the levels reported by healthy children or mental health controls. Parents of 214 children (137 "healthy" children, 27 children using mental health services and 40 children with ABI) aged 9-15 years participated. A questionnaire measure of peer-relationship functioning and emotional distress was completed. Children with ABI experienced a greater degree of peer-relationship difficulties and emotional distress than healthy controls. No difference was found in reported peer relationship difficulties or emotional distress between ABI children and the children accessing mental health services. We conclude that emotional distress and co-occurring peer-relationship difficulties are as prevalent in a population of children after ABI as may be expected in a population of children under the care of mental health services, yet, unlike the latter group, appropriate intervention services are not commonly available. Interventions that aim to enhance peer relationships after childhood ABI may provide an essential resource to the benefit of outcome.

Novel class of LIM-kinase 2 inhibitors for the treatment of ocular hypertension and associated glaucoma.

The discovery of a pyrrolopyrimidine class of LIM-kinase 2 (LIMK2) inhibitors is reported. These LIMK2 inhibitors show good potency in enzymatic and cellular assays and good selectivity against ROCK. After topical dosing to the eye in a steroid induced mouse model of ocular hypertension, the compounds reduce intraocular pressure to baseline levels. The compounds also increase outflow facility in a pig eye perfusion assay. These results suggest LIMK2 may be an effective target for treating ocular hypertension and associated glaucoma.

The development of emotion and empathy skills after childhood brain injury.

Lasting socio-emotional behaviour difficulties are common among children who have suffered brain injuries. A proportion of difficulties may be attributed to impaired cognitive and/or executive skills after injury. A recent and rapidly accruing body of literature indicates that deficits in recognizing and responding to the emotions of others are also common. Little is known about the development of these skills after brain injury. In this paper we summarize emotion-processing systems, and review the development of these systems across the span of childhood and adolescence. We describe critical phases in the development of emotion recognition skills and the potential for delayed effects after brain injury in earlier childhood. We argue that it is important to identify the specific nature of deficits in reading and responding to emotions after brain injury, so that assessments and early intervention strategies can be devised.

Visual-spatial functioning as an early indicator of socioemotional difficulties.

PRIMARY OBJECTIVE: As children with acquired brain injuries (ABI) mature to become adolescents they develop a range of previously undetected social and emotional difficulties, which are commonly associated with executive dysfunctions. The authors wanted to determine whether visual-spatial performance is subject to age-related improvement, whether such skills can differentiate between children with ABI and healthy children and whether visual-spatial performance is a correlate of socioemotional functioning. RESEARCH DESIGN: The 'Cube analysis' and 'Dot discrimination' tests from the 'Visual Object Space Perception (VOSP)' battery and the Strengths and Difficulties Questionnaire (SDQ) were administered for 18 children, 9-15 years, with ABI and compared against 67 'healthy' children. RESULTS: Cube analysis scores improved significantly at approximately 10 years old in the control group. The ABI group performed the task significantly poorer than controls. Analysis indicated that visual discrimination skill did not account for performance difficulties. Visual-spatial performance was correlated with greater impact of reported difficulties on the SDQ. CONCLUSIONS: Visual-spatial tests are sensitive in differentiating between healthy children and children with ABI. Impairment of visuo-spatial skills may provide an index of psychosocial risk during later teenage years and adulthood.

Reading emotions after childhood brain injury: case series evidence of dissociation between cognitive abilities and emotional expression processing skills.

PRIMARY OBJECTIVE: A previous study has shown that children with brain injuries are worse than their same age peers at reading emotions. It has not clearly been established that cognitive impairments and emotion processing impairments are dissociable in children and the question of whether emotion-reading skills can be selectively impaired in children after brain injury is explored here. RESEARCH DESIGN: This study addresses this issue by testing a case series of seven children with brain injuries, who were identified as experiencing emotional or behavioural difficulties, according to a social-behavioural measure. METHODS AND PROCEDURES: A battery of tests of cognitive function and measures that assess ability in reading emotions from faces, voices and eyes was administered to each child. MAIN OUTCOMES AND RESULTS: Some cases demonstrate broadly based deficits that affect both cognitive and emotion processing domains, whilst other cases demonstrate highly selective deficits in reading emotions. CONCLUSIONS: Based on the profile of results across the cases, this study reports that modality-specific, selective impairments in reading emotional expression can be found in children after brain injury. In addition, the data provide evidence of dissociation between cognitive abilities and emotional expression processing.

Traumatic brain injury and the construction of identity: a discursive approach.

Using discourse analysis, this paper explores the co-construction of identity for individuals who have sustained a severe traumatic brain injury (TBI). An analysis of discourse, obtained through interviewing six adults with a TBI, each with one or two significant others, suggested four main interpretative repertoires which informed participants' co-construction of identity: "Medical model referencing", "dependence as intrinsic to TBI", "TBI as deficit" and "progression and productivity as key life-defining features". Medical model referencing is discussed in relation to the common, passive positioning of individuals with TBI, which often occurred in relation to memory loss. The construction of abandonment was also common, due to participants" dependence on the provision of specialist, expert services in the community. Clinical implications are discussed in terms of facilitating individuals in the co-constructing and re-authorship of more empowering and inclusive narratives and providing community services that promote meaningful social identities, separate from medical discourse.

Reading emotions after child brain injury: a comparison between children with brain injury and non-injured controls.

PRIMARY OBJECTIVE: Child brain injury can have a lasting, detrimental effect upon socio-emotional behaviour, but little is known about underlying impairments that cause behavioural disturbance. This study explored the possibility that a proportion of difficulties result from compromise to systems in the brain which function in reading emotion in others from eyes, face expression or vocal tone. METHODS AND PROCEDURES: Measures of ability in reading emotion from faces, voices and eyes were used in conjunction with a battery of tests of cognitive function, in gathering data from 18 children aged between 9-17 with acquired brain injuries (ABI). Performance levels were compared against the normative data from 67 matched 'healthy' children. Questionnaires were used as a measure of socio-emotional behaviour. MAIN OUTCOMES AND RESULTS: The ABI children in the sample were worse than their same age peers at reading emotions. Regression analyses revealed that emotion recognition skills and cognitive abilities were generally unrelated. Some relationships between emotion reading difficulties and behaviour disturbance were found, however there were limitations associated with this particular finding. CONCLUSIONS: Emotion-recognition skills, which are not routinely assessed following child brain injury, can be adversely affected as a consequence of brain injury in childhood.

Assessing emotion recognition in 9-15-years olds: preliminary analysis of abilities in reading emotion from faces, voices and eyes.

PRIMARY OBJECTIVE: Little is known about how emotion recognition abilities develop during childhood and adolescence, although adolescence is a time marked by significant changes in socio-emotional behaviour. The first aim of this study was to explore the range of emotion recognition skills that 9-15-year olds would normally display and whether emotion-reading skills are reliably measurable. Secondly, one wanted to determine whether adolescence is a period during which skills in recognizing emotions improve. METHODS AND PROCEDURES: Novel and adapted measures of emotion processing were used in tasks that required 67 9-15-year olds to read emotion from voices, eyes and faces. MAIN OUTCOMES AND RESULTS: Findings indicate that emotion recognition abilities are reliably measurable skills. A stage of improvement in facial expression recognition and reading emotion from eyes was found to occur at approximately 11 years of age. CONCLUSIONS: The findings show that these skills can be measured and that it is possible to devise assessment tests which are sensitive to developmental improvements in emotion recognition skills in early adolescence, when screening for the effects of child brain injury.

Association of neuregulin 1 with schizophrenia confirmed in a Scottish population.

Recently, we identified neuregulin 1 (NRG1) as a susceptibility gene for schizophrenia in the Icelandic population, by a combined linkage and association approach. Here, we report the first study evaluating the relevance of NRG1 to schizophrenia in a population outside Iceland. Markers representing a core at-risk haplotype found in Icelanders at the 5' end of the NRG1 gene were genotyped in 609 unrelated Scottish patients and 618 unrelated Scottish control individuals. This haplotype consisted of five SNP markers and two microsatellites, which all appear to be in strong linkage disequilibrium. For the Scottish patients and control subjects, haplotype frequencies were estimated by maximum likelihood, using the expectation-maximization algorithm. The frequency of the seven-marker haplotype among the Scottish patients was significantly greater than that among the control subjects (10.2% vs. 5.9%, P=.00031). The estimated risk ratio was 1.8, which is in keeping with our report of unrelated Icelandic patients (2.1). Three of the seven markers in the haplotype gave single-point P values ranging from .000064 to .0021 for the allele contributing to the at-risk haplotype. This direct replication of haplotype association in a second population further implicates NRG1 as a factor that contributes to the etiology of schizophrenia.