Visual memory profile in 22q11.2 microdeletion syndrome: are there differences in performance and neurobiological substrates between tasks linked to ventral and dorsal visual brain structures? A cross-sectional and longitudinal study

Background

Children affected by the 22q11.2 deletion syndrome (22q11.2DS) have a specific neuropsychological profile with strengths and weaknesses in several cognitive domains. Specifically, previous evidence has shown that patients with 22q11.2DS have more difficulties memorizing faces and visual-object characteristics of stimuli. In contrast, they have better performance in visuo-spatial memory tasks. The first focus of this study was to replicate these results in a larger sample of patients affected with 22q11.2DS and using a range of memory tasks. Moreover, we analyzed if the deficits were related to brain morphology in the structures typically underlying these abilities (ventral and dorsal visual streams). Finally, since the longitudinal development of visual memory is not clearly characterized in 22q11.2DS, we investigated its evolution from childhood to adolescence.

Methods

Seventy-one patients with 22q11.2DS and 49 control individuals aged between 9 and 16 years completed the Benton Visual Retention Test (BVRT) and specific subtests assessing visual memory from the Children’s Memory Scale (CMS). The BVRT was used to compute spatial and object memory errors. For the CMS, specific subtests were classified into ventral, dorsal, and mixed subtests. Longitudinal data were obtained from a subset of 26 patients and 22 control individuals.

Results

Cross-sectional results showed that patients with 22q11.2DS were impaired in all visual memory measures, with stronger deficits in visual-object memory and memory of faces, compared to visuo-spatial memory. No correlations between morphological brain impairments and visual memory were found in patients with 22q11.2DS. Longitudinal findings revealed that participants with 22q11.2DS made more object memory errors than spatial memory errors at baseline. This difference was no longer significant at follow-up.

Conclusions

Individuals with 22q11.2DS have impairments in visual memory abilities, with more pronounced difficulties in memorizing faces and visual-object characteristics. From childhood to adolescence, the visual cognitive profile of patients with 22q11.2DS seems globally stable even though some processes show an evolution with time. We hope that our results will help clinicians and caregivers to better understand the memory difficulties of young individuals with 22q11.2DS. This has a particular importance at school to facilitate recommendations concerning intervention strategies for these young patients.

     

Polyamines are traps for reactive intermediates in furan metabolism

Furan is toxic and carcinogenic in rodents. Because of the large potential for human exposure, furan is classified as a possible human carcinogen. The detailed mechanism by which furan causes toxicity and cancer is not yet known. Since furan toxicity requires cytochrome P450-catalyzed oxidation of furan, we have characterized the urinary and hepatocyte metabolites of furan to gain insight into the chemical nature of the reactive intermediate. Previous studies in hepatocytes indicated that furan is oxidized to the reactive α,β-unsaturated dialdehyde, cis-2-butene-1,4-dial (BDA), which reacts with glutathione (GSH) to form 2-(S-glutathionyl)succinaldehyde (GSH-BDA). This intermediate forms pyrrole cross-links with cellular amines such as lysine and glutamine. In this article, we demonstrate that GSH-BDA also forms cross-links with ornithine, putrescine, and spermidine when furan is incubated with rat hepatocytes. The relative levels of these metabolites are not completely explained by hepatocellular levels of the amines or by their reactivity with GSH-BDA. Mercapturic acid derivatives of the spermidine cross-links were detected in the urine of furan-treated rats, which indicates that this metabolic pathway occurs in vivo. Their detection in furan-treated hepatocytes and in urine from furan-treated rats indicates that polyamines may play an important role in the toxicity of furan.     

TGF-�� isoforms inhibit IGF-1-induced migration and regulate terminal differentiation in a cell-specific manner

Following muscle injury, the damaged tissue and influx of inflammatory cells stimulate the secretion of growth factors and cytokines to initiate repair processes. This release of chemotactic signaling factors activates resident precursor cells and stimulates their mobilization and migration to the site of injury where terminal differentiation can occur. The three transforming growth factor-β (TGF-β) isoforms, and insulin-like growth factor-1 (IGF-1) are among the known regulatory factors released following muscle damage. We investigated the effect of recombinant active TGF-β1, -β2, -β3 and IGF-1 on C2C12 skeletal muscle satellite cell and P19 embryonal carcinoma cell terminal differentiation and migration. C2C12 myoblast fusion as well as P19 embryoid body formation and myogenic differentiation was assessed following 72?h TGF-β treatment (5?ng/ml), whereas the effect of the TGF-β isoforms on migration was determined following 7?h incubation. Our results showed that TGF-β decreases C2C12 myoblast fusion in an isoform-independent manner, whereas in the P19 cell lineage, results demonstrate that TGF-β1 specifically and significantly increased P19 embryoid body formation, but not expression of Connexin-43 or Myosin Heavy Chain. IGF-1 significantly increased migration compared to TGF-β isoforms, which, on their own, had no significant effect on the mobilization of either C2C12 or P19 cells. TGF-β isoforms decreased IGF-1-induced migration of both cell lineages. By distinguishing the factors involved in, and the molecular signals required for, myoblast recruitment during repair processes, strategies can be developed towards improved cell-mediated therapies for muscle injury.     

Enteric-coated mycophenolate sodium in de novo pediatric renal transplant patients

Data on the use of enteric-coated mycophenolic acid (EC-MPS) in pediatric transplantation cases are scarce. We undertook a 12-month, multicenter, open-label pilot study in which 16 de novo renal transplant patients aged 5–16 years received EC-MPS with cyclosporine A microemulsion (CsA-ME), steroids, and anti-interleukin-2 receptor antibody induction. The mean dose of EC-MPS was 916 ± 93 mg/m² per day during weeks 1–2, 810 ± 193 mg/m² per day during months 3–6, and 827 ± 153 mg/m² per day during months 6–12. The mean CsA C₂ level exceeded target range up to month 6 post-transplant. Efficacy failure (biopsy-proven acute rejection, graft loss, death or loss to follow-up) occurred in two patients: one patient with primary non-function underwent nephrectomy, and one patient experienced biopsy-proven acute rejection (Grade 1B, day 344) following EC-MPS dose reduction. There were no deaths. Creatinine clearance (Schwartz) was 103 ± 30 mL/min per 1.73 m² at month 6 and 100 ± 16 mL/min per 1.73 m² at month 12. The majority of adverse events were mild or moderate (101/126, 80.2%). In this pilot study, EC-MPS 450 mg/m² administered twice daily with CsA, steroids, and interleukin-2 antibody induction resulted in a low rate of rejection with good renal function in a pediatric population. However, a larger, controlled trial is required to confirm these results.     

Computerized ambulatory monitoring in psychiatry: a multi‐site collaborative study of acceptability,compliance, and reactivity

Computerized ambulatory monitoring overcomes a number of methodological and conceptual challenges to studying mental disorders, however concerns persist regarding the feasibility of this approach with severe psychiatric samples and the potential of intensive monitoring to influence data quality. This multi‐site investigation evaluates these issues in four independent samples. Patients with schizophrenia (n = 56), substance dependence (n = 85), anxiety disorders (n = 45), and a non‐clinical sample (n = 280) were contacted to participate in investigations using computerized ambulatory monitoring. Micro‐computers were used to administer electronic interviews several times per day for a one‐week period. Ninety‐five percent of contacted individuals agreed to participate in the study, and minimum compliance was achieved by 96% of these participants. Seventy‐eight percent of all programmed assessments were completed overall, and only 1% of micro‐computers were not returned to investigators. There was no evidence that missing data or response time increased over the duration of the study, suggesting that fatigue effects were negligible. The majority of variables investigated did not change in frequency as a function of study duration, however some evidence was found that socially sensitive behaviors changed in a manner consistent with reactivity. Copyright © 2009 John Wiley & Sons, Ltd.     

Panel review of anaplastic oligodendroglioma from European Organization For Research and Treatment of Cancer Trial 26951: assessment of consensus in diagnosis, influence of 1p/19q loss, and correlations with outcome

The diagnosis of anaplastic oligodendroglioma (AOD) or anaplastic oligoastrocytoma (AOA) is subject to interobserver variation. The aim of this study was to estimate consensus in typing and grading of these tumors using tumor material collected in a large prospective randomized phase III study and to correlate the consensus diagnosis with the 1p/19q status of the tumors and the clinical outcome. The available pathology material of the first 150 patients, randomized into the European Organization for Research and Treatment of Cancer Trial 26951, was reviewed by an independent panel of 9 neuropathologists. The presence of deletions of 1p and 19q was assessed by fluorescence in situ hybridization with locus-specific probes. The panel reached consensus on the diagnosis of AOD in 52% of the tumors that had been diagnosed as AOD by the local pathologists, whereas only 8% of the local diagnosis of AOA was confirmed with consensus. The concordance on the panel diagnosis of AOD was high (intraclass correlation = 86%). The survival curves for AOD with 1p/19q loss, AOD without these losses, and AOA without 1p/19q loss ran separately in this order. The absence of necrosis and the presence of endothelial abnormalities were correlated with better outcomes. In multivariate analysis, patients' age, 1p/19q loss, and necrosis were identified as independent prognostic factors.     

Clinically suspected acute recurrent pulmonary embolism: a diagnostic challenge

It is unknown whether strategies validated for diagnosing pulmonary embolism (PE) are valid in patients with a history of PE. It was the objective of this study to investigate whether a diagnostic algorithm consisting of sequential application of a clinical decision rule (CDR), a quantitative D-dimer test and computed tomography (CT) safely ruled out a clinical suspicion of acute recurrent PE. Data were obtained from a diagnostic outcome study of patients suspected of PE. Acute recurrent PE was ruled out by an unlikely probability of PE (CDR score 相似文献