Early Neurodevelopmental Findings Predict School Age Cognitive Abilities in Duchenne Muscular Dystrophy: A Longitudinal Study

Objective

Neurodevelopmental and cognitive difficulties are known to occur frequently in boys with Duchenne muscular dystrophy but so far none of the published studies have reported both early neurodevelopmental assessments and cognitive tests in the same cohort. The aim of the present longitudinal study was to establish the correlation between early neurodevelopmental assessments performed in preschool boys and the cognitive scales performed at school age or later.

Methods

We performed cognitive tests at school age (mean age 5.7 year ±1.7 SD) (69 months+19 SD) in a cohort of Duchenne boys, previously assessed using the Griffiths scales before the age of 4 years (mean age when the Griffiths scales were performed 30 months ±8.9 SD).

Results

The range of total Developmental quotients on the Griffiths ranged between 56 and 116 (mean 89 ± 15.6 SD). The total Intelligence Quotients on the Wechsler scales ranged between 35 and 119 (mean 87 ± 17.2 SD). There was a significant correlation between the findings on the two scales. P = <0.0001. When we subdivided the cohort according to site of mutations, there was a difference between boys with mutations upstream exon 44 and those with mutations in exon 44–45 affecting Dp140 on both Developmental and Intelligence Quotient (p 0.01 and p 0,003 respectively).

Conclusions

Our results confirm that Duchenne boys tend to slightly underperform on both neurodevelopmental and cognitive assessments. Early neurodevelopmental findings correlated with the cognitive results obtained at school age with a clear concordance between subscales exploring similar domains on the two scales.     

Lessons for the clinic from rituximab pharmacokinetics and pharmacodynamics

The anti-CD20 antibody rituximab (RTX; Rituxan®, MabThera®) was the first anti-cancer antibody approved by the US Food and Drug Administration in 1997 and it is now the most-studied unconjugated therapeutic antibody. The knowledge gained over the past 15 y on the pharmacodynamics (PD) of this antibody has led to the development of a new generation of anti-CD20 antibodies with enhanced efficacy in vitro. Studies on the pharmacokinetics (PK) properties and the effect of factors such as tumor load and localization, antibody concentration in the circulation and gender on both PK and clinical response has allowed the design of optimized schedules and novel routes of RTX administration. Although clinical results using newer anti-CD20 antibodies, such as ofatumumab and obinutuzumab, and novel administration schedules for RTX are still being evaluated, the knowledge gained so far on RTX PK and PD should also be relevant for other unconjugated monoclonal antibody therapeutics, and will be critically reviewed here.     

First Report of Phytophthora Foliar Blight on Florida Hopbush (Dodonaea viscosa) in Italy

During 2010, a new foliar blight was detected on potted Dodonaea viscosa cv. Purpurea plants in two nurseries in Catania (Italy). On the basis of morphological and cultural features, the pathogen was identified as Phytophthora palmivora. The internal transcribed spacer (ITS)‐rDNA sequence of a representative Phytophthora isolate from hopbush showed 99% identity with other ITS sequences of different P. palmivora isolates available in GenBank, thus confirming the morpho‐cultural identification. Koch’s postulates were fulfilled by pathogenicity tests on potted D. viscosa cv. Purpurea seedlings. To our knowledge, this is the first report of P. palmivora foliar blight disease on D. viscosa.     

Cross-species toxicogenomic analyses and phenotypic anchoring in response to groundwater low-level pollution

Background

Comparison of toxicogenomic data facilitates the identification of deregulated gene patterns and maximizes health risk prediction in human.

Results

Here, we performed phenotypic anchoring on the effects of acute exposure to low-grade polluted groundwater using mouse and zebrafish. Also, we evaluated two windows of chronic exposure in mouse, starting in utero and at the end of lactation. Bioinformatic analysis of livers microarray data showed that the number of deregulated biofunctions and pathways is higher after acute exposure, compared to the chronic one. It also revealed specific profiles of altered gene expression in all treatments, pointing to stress response/mitochondrial pathways as major players of environmental toxicity. Of note, dysfunction of steroid hormones was also predicted by bioinformatic analysis and verified in both models by traditional approaches, serum estrogens measurement and vitellogenin mRNA determination in mice and zebrafish, respectively.

Conclusions

In our report, phenotypic anchoring in two vertebrate model organisms highlights the toxicity of low-grade pollution, with varying susceptibility based on exposure window. The overlay of zebrafish and mice deregulated pathways, more than single genes, is useful in risk identification from chemicals implicated in the observed effects.

Electronic supplementary material

The online version of this article (doi:10.1186/1471-2164-15-1067) contains supplementary material, which is available to authorized users.     

Response of rocket salad germplasm (Eruca and Diplotaxis spp.) to major pathogens causing damping-off,wilting and leaf spot diseases

In the present study, 26 accessions of rocket salad belonging to four species (Eruca sativa Mill., Diplotaxis tenuifolia (L.) DC., Diplotaxis muralis (L.) DC. and Erucastrum spp.) were tested for resistance to damping-off, wilting and leaf spot disease causal agents. High susceptibility to Rhizoctonia solani was detected in all accessions while variability in rocket seedling susceptibility for Sclerotinia assays was observed. Susceptibility to wilting caused by the fungus Fusarium oxysporum f. sp. raphani was tested. E. sativa varieties exhibited a lower severity degree associated to yellowing-related symptoms compared to D. tenuifolia. Resistance assay using the bacterium Xanthomonas campestris pv. campestris was also performed. Five E. sativa varieties showed a disease incidence lower than 60% while all the D. tenuifolia accessions, showed a susceptibility of 100%. The present study represents a step towards the identification of genetic resources useful in breeding for the selections of novel resistant varieties.     

Ecology of planktonic heterotrophic flagellates. A review.

In aquatic environments heterotrophic flagellates are an important component within the microbial loop and the food web, owing to their involvement in the energy transfer and flux and as an intermediate link between bacteria and primary producers, and greater organisms, such as other protists and metazoan consumers. In the microbial loop heterotrophic flagellates highly contribute to fast biomass and nutrient recycling and to the production in aquatic environments. In fact, these protists consume efficiently viruses, bacteria, cyanobacteria and picophytoplankton, and are grazed mainly by other protists, rotifers and small crustaceans. In this paper the knowledge about these unicellular organisms is reviewed, taking into particular account their ecological relationships and trophic role within the plankton community of marine and freshwater environments.