Sequential extracellular matrix-focused and baited-global cluster analysis of serial transcriptomic profiles identifies candidate modulators of renal tubulointerstitial fibrosis in murine adriamycin-induced nephropathy

Transcriptome analysis using microarray technology represents a powerful unbiased approach for delineating pathogenic mechanisms in disease. Here molecular mechanisms of renal tubulointerstitial fibrosis (TIF) were probed by monitoring changes in the renal transcriptome in a glomerular disease-dependent model of TIF ( adriamycin nephropathy) using Affymetrix (mu74av2) microarray coupled with sequential primary biological function-focused and secondary

Impaired conflict resolution and alerting in children with ADHD: evidence from the Attention Network Task (ANT)

An important theory of attention suggests that there are three separate networks that execute discrete cognitive functions. The 'alerting' network acquires and maintains an alert state, the 'orienting' network selects information from sensory input and the 'conflict' network resolves conflict that arises between potential responses. This theory holds promise for dissociating discrete patterns of cognitive impairment in disorders where attentional deficits may often be subtle, such as in attention deficit hyperactivity disorder (ADHD).

Absence of the 7-repeat variant of the DRD4 VNTR is associated with drifting sustained attention in children with ADHD but not in controls

Many genetic studies have demonstrated an association between the 7-repeat (7r) allele of a 48-base pair variable number of tandem repeats (VNTR) in exon 3 of the DRD4 gene and the phenotype of attention deficit hyperactivity disorder (ADHD). Previous studies have shown inconsistent associations between the 7r allele and neurocognitive performance in children with ADHD. We investigated the performance of 128 children with and without ADHD on the Fixed and Random versions of the Sustained Attention to Response Task (SART). We employed timeseries analyses of reaction-time data to allow a fine-grained analysis of reaction time variability, a candidate endophenotype for ADHD. Children were grouped into either the 7r-present group (possessing at least one copy of the 7r allele) or the 7r-absent group. The ADHD group made significantly more commission errors and was significantly more variable in RT in terms of fast moment-to-moment variability than the control group, but no effect of genotype was found on these measures. Children with ADHD without the 7r allele made significantly more omission errors, were significantly more variable in the slow frequency domain and showed less sensitivity to the signal (d') than those children with ADHD the 7r and control children with or without the 7r. These results highlight the utility of time-series analyses of reaction time data for delineating the neuropsychological deficits associated with ADHD and the DRD4 VNTR. Absence of the 7-repeat allele in children with ADHD is associated with a neurocognitive profile of drifting sustained attention that gives rise to variable and inconsistent performance. (c) 2008 Wiley-Liss, Inc.

Psychological problems in children with hemiplegia: a European multicentre survey

Objective: To describe the prevalence and determinants of psychological problems in European children with hemiplegia. Design: Cross-sectional survey. Setting: Home visits in nine European regions by research associates who administered standard questionnaires to parents. Patients: 279 children with hemiplegia aged 8–12 years were recruited from population-based case registers. Outcome measure: Strengths and Difficulties Questionnaire comprising emotion, conduct, hyperactivity, peer problems and prosocial domains. An “impact score” (IS) measures the social and psychological impact of the child’s difficulties. Results: Children with hemiplegia had higher mean scores on the total difficulties score (TDS) compared with a normative sample (p<0.001). 48% and 57% of children, respectively, had borderline–abnormal TDS and IS. Significant, independent associations were observed between intellectual impairment and an increased risk for hyperactivity (odds ratio; OR 8.4, 95% CI 3.4 to 20.8), peer problems (OR 3.1, 95% CI 1.7 to 5.5), psychological and social impact (OR 3.0, 95% CI 1.6 to 5.6) when children with an intellectual quotient (IQ) <50 were compared with those with an IQ >70. Boys had an increased risk for conduct (OR 2.1, 95% CI 1.2 to 3.7) and hyperactivity disorders (OR 2.5, 95% CI 1.4 to 4.6). Poor self-esteem was associated with an increased risk for peer problems (OR 5.8, 95% CI 2.5 to 13.4) and poor prosocial skills (OR 7.5, 95% CI 2.4 to 23.2) compared with those with high self-esteem. Other determinants of psychological adjustment were impaired communication, severe pain and living with a single parent. Conclusions: Many of the psychological problems identified are amenable to treatment. Special attention should be given to those at highest risk of developing psychological difficulties.

Shyness and face scanning in children

Contrary to popular beliefs, a recent empirical study using eye tracking has shown that a non-clinical sample of socially anxious adults did not avoid the eyes during face scanning. Using eye-tracking measures, we sought to extend these findings by examining the relation between stable shyness and face scanning patterns in a non-clinical sample of 11-year-old children. We found that shyness was associated with longer dwell time to the eye region than the mouth, suggesting that some shy children were not avoiding the eyes. Shyness was also correlated with fewer first fixations to the nose, which is thought to reflect the typical global strategy of face processing. Present results replicate and extend recent work on social anxiety and face scanning in adults to shyness in children. These preliminary findings also provide support for the notion that some shy children may be hypersensitive to detecting social cues and intentions in others conveyed by the eyes. Theoretical and practical implications for understanding the social cognitive correlates and treatment of shyness are discussed. (C) 2009 Elsevier Ltd. All rights reserved.

Pepsin measured in induced sputum - a test for pulmonary aspiration in children?

Purpose The purpose of this study was to investigate if pepsin measured in sputum is a useful marker of pulmonary aspiration secondary to gastroesophageal reflux (GER) in children. It is possible that the induced sputum procedure could cause GER and invalidate the results. The hypothesis stated that healthy children (those without history of respiratory or gastroesophageal symptoms) would not have pepsin detected in induced sputum. Methods Children attending surgical outpatients in the Royal Belfast Hospital for Sick Children (Belfast, Northern Ireland) were recruited. After spirometry, sputum was obtained by induction with hypertonic 3% saline. Spirometry was repeated, and complications were noted. An “in-house” enzyme-linked immunosorbent assay was used to measure pepsin concentration in sputum. The lower limit of detection of pepsin was 1.19 ng/mL. Results Children (n = 21) aged 4 to 16 years were recruited. Twenty children completed the study. No adverse effects were reported. Pepsin was detected in 17 (85%) of 20 sputum samples. Conclusions The act of sputum induction appears to induce physiologic GER in a healthy childhood population. The analysis of pepsin in sputum obtained by sputum induction is therefore not useful in the investigation of reflux-related respiratory disease.

Implementation of European standards of care for cystic fibrosis - provision of care

Background: Several guidelines for cystic fibrosis (CF) caregivers exist, but information about their implementation is lacking.

Implementation of European standards of care for cystic fibrosis - Control and treatment of infection

Background: Several guidelines oil infection control and treatment of infection exist for cystic fibrosis (CF) caregivers, although the extent of implementation is variable.

Copying letters to patients with cystic fibrosis (CF): Letter content and patient perceptions of benefit

Background: Copying letters involves generating an extra copy of all correspondence between healthcare professionals about the patient, to the patient.