104 research outputs found

    Comparing attention to socially-relevant stimuli in autism spectrum disorder and developmental coordination disorder

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    Difficulties with social interaction have been reported in both children with an autism spectrum disorder (ASD) and children with developmental coordination disorder (DCD), although these disorders have very different diagnostic characteristics. To date, assessment of social skills in a DCD population has been limited to paper-based assessment or parent report. The present study employed eye tracking methodology to examine how children attend to socially-relevant stimuli, comparing 28 children with DCD, 28 children with ASD and 26 typically-developing (TD) age-matched controls (aged 7-10). Eye movements were recorded while children viewed 30 images, half of which were classed as ‘Individual’ (one person in the scene, direct gaze) and the other half were ‘Social’ (more naturalistic scenes showing an interaction). Children with ASD spent significantly less time looking at the face/eye regions in the images than TD children, but children with DCD performed between the ASD and TD groups in this respect. Children with DCD demonstrated a reduced tendency to follow gaze, in comparison to the ASD group. Our findings confirm that social atypicalities are present in both ASD and to a lesser extent DCD, but follow a different pattern. Future research would benefit from considering the developmental nature of the observed findings and their implications for support

    Future potential of metagenomics in clinical laboratories

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    INTRODUCTION: Rapid and sensitive diagnostic strategies are necessary for patient care and public health. Most of the current conventional microbiological assays detect only a restricted panel of pathogens at a time or require a microbe to be successfully cultured from a sample. Clinical metagenomics next-generation sequencing (mNGS) has the potential to unbiasedly detect all pathogens in a sample, increasing the sensitivity for detection and enabling the discovery of unknown infectious agents. AREAS COVERED: High expectations have been built around mNGS; however, this technique is far from widely available. This review highlights the advances and currently available options in terms of costs, turnaround time, sensitivity, specificity, validation, and reproducibility of mNGS as a diagnostic tool in clinical microbiology laboratories. EXPERT OPINION: The need for a novel diagnostic tool to increase the sensitivity of microbial diagnostics is clear. mNGS has the potential to revolutionise clinical microbiology. However, its role as a diagnostic tool has yet to be widely established, which is crucial for successfully implementing the technique. A clear definition of diagnostic algorithms that include mNGS is vital to show clinical utility. Similarly to real-time PCR, mNGS will one day become a vital tool in any testing algorithm

    Genomic characterization of coxsackievirus A22 from a regional university hospital in the Netherlands

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    Background: Enteroviruses are highly diverse with a wide spectrum of genotypes and clinical manifestations. Coxsackievirus A22 (CVA22) has been detected globally from sewage surveillance; however, currently there is limited information on its prevalence in patients, as well as available genomic data. Objective: We aimed to provide genomic and relative frequency data on CVA22 from a regional hospital perspective between 2013-2020. Study design: Sanger sequencing was performed on all samples with a positive enterovirus RT-qPCR result ( 3 weeks). Furthermore, we report the first two near-complete CVA22 sequences from Europe, which grouped with a strain previously isolated from Bangladesh in 1999. Conclusions: We show a highly diverse enterovirus genotype which causes infections annually, typically in autumn and winter, and is capable of recurrent infection in an immunocompromised patient. Furthermore, we highlight the use of NGS to complement conventional targeted Sanger sequencing

    Early and persistent motor delay in infants at-risk of developing autism spectrum disorder: A prospective study

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    The aim was to build a profile of motor development in infant siblings of children diagnosed with autism. Infants at high familial risk of developing autism spectrum disorder and those at low-risk were tested longitudinally between 6 and 24 months. Data were analysed from the gross and fine motor scales of the Mullen Scales of Early Learning and the Vineland Adaptive Behavior Scales at three age points. Low-risk and at-risk infants differed significantly on motor scales at all three visits, with significantly lower motor scores in the at-risk group evident from the age of 6 months based on parental report. Poorer gross and fine motor skills in the at-risk group were only evident on the direct standardised assessment from 12 months. Only gross motor scores were highly correlated across the two measures. A combination of standardised assessments and parental reports may therefore provide the best method for early identification of motor atypicalities in the broader autism phenotype

    Exploring a prolonged enterovirus C104 infection in a severely ill patient using nanopore sequencing

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    Chronic enterovirus infections can cause significant morbidity, particularly in immunocompromised patients. This study describes a fatal case associated with a chronic untypeable enterovirus infection in an immunocompromised patient admitted to a Dutch university hospital over nine months. We aimed to identify the enterovirus genotype responsible for the infection and to determine potential evolutionary changes. Long-read sequencing was performed using viral targeted sequence capture on four respiratory and one faecal sample. Phylogenetic analysis was performed using a maximum likelihood method, along with a root-to-tip regression and time-scaled phylogenetic analysis to estimate evolutionary changes between sample dates. Intra-host variant detection, using a Fixed Ploidy algorithm, and selection pressure, using a Fixed Effect Likelihood and a Mixed Effects Model of Evolution, were also used to explore the patient samples. Near-complete genomes of enterovirus C104 (EV-C104) were recovered in all respiratory samples but not in the faecal sample. The recovered genomes clustered with a recently reported EV-C104 from Belgium in August 2018. Phylodynamic analysis including ten available EV-C104 genomes, along with the patient sequences, estimated the most recent common ancestor to occur in the middle of 2005 with an overall estimated evolution rate of 2.97 × 10(−3) substitutions per year. Although positive selection pressure was identified in the EV-C104 reference sequences, the genomes recovered from the patient samples alone showed an overall negative selection pressure in multiple codon sites along the genome. A chronic infection resulting in respiratory failure from a relatively rare enterovirus was observed in a transplant recipient. We observed an increase in single-nucleotide variations between sample dates from a rapidly declining patient, suggesting mutations are weakly deleterious and have not been purged during selection. This is further supported by the persistence of EV-C104 in the patient, despite the clearance of other viral infections. Next-generation sequencing with viral enrichment could be used to detect and characterise challenging samples when conventional workflows are insufficient

    First detection of porcine respirovirus 1 in Germany and the Netherlands

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    Porcine respirovirus 1, also referred to as porcine parainfluenza virus 1 (PPIV-1), was first detected in deceased pigs from Hong Kong in 2013. It has since then been found in the USA, Chile and most recently in Hungary. Information on the pathogenicity and global spread is sparse. However, it has been speculated to play a role in the porcine respiratory disease complex. To investigate the porcine virome, we screened 53 pig samples from 26 farms within the Dutch-German border region using shotgun metagenomics sequencing (SMg). After detecting PPIV-1 in five farms through SMg, a real-time reverse transcriptase PCR (RT-qPCR) assay was designed, which not only confirmed the presence of the virus in 1 of the 5 farms but found an additional 6 positive farms. Phylogenetic analysis found the closest match to be the first detected PPIV-1 strain in Hong Kong. The Dutch-German region represents a significant area of pig farming within Europe and could provide important information on the characterization and circulation of porcine viruses, such as PPIV-1. With its recent detection in Hungary, these findings suggest widespread circulation of PPIV-1 in Central Europe, highlighting the need for further research on persistence, pathogenicity and transmission in Europe

    Assessment of Viral Targeted Sequence Capture Using Nanopore Sequencing Directly from Clinical Samples

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    Shotgun metagenomic sequencing (SMg) enables the simultaneous detection and characterization of viruses in human, animal and environmental samples. However, lack of sensitivity still poses a challenge and may lead to poor detection and data acquisition for detailed analysis. To improve sensitivity, we assessed a broad scope targeted sequence capture (TSC) panel (ViroCap) in both human and animal samples. Moreover, we adjusted TSC for the Oxford Nanopore MinION and compared the performance to an SMg approach. TSC on the Illumina NextSeq served as the gold standard. Overall, TSC increased the viral read count significantly in challenging human samples, with the highest genome coverage achieved using the TSC on the MinION. TSC also improved the genome coverage and sequencing depth in clinically relevant viruses in the animal samples, such as influenza A virus. However, SMg was shown to be adequate for characterizing a highly diverse animal virome. TSC on the MinION was comparable to the NextSeq and can provide a valuable alternative, offering longer reads, portability and lower initial cost. Developing new viral enrichment approaches to detect and characterize significant human and animal viruses is essential for the One Health Initiative

    The role of older siblings in infant motor development

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    Previous research has suggested that infant motor skills may be affected by older siblings, but has not considered whether this is due to specific characteristics of the older sibling, or of the quality of the sibling relationship. The current study used a longitudinal diary method to record infant motor milestones from 23 infants with older siblings, along with parent reports and standardised assessments of motor skills. Parent reports of the older siblings’ motor skills and the sibling relationship were also collected until the infants were 18 months old. The motor skills, age, and sex of the older siblings were not significantly related to any measure of infant motor development. A significant correlation was revealed between perceived agonism between siblings and infant fine motor skills at 18 months, suggesting the importance of considering reciprocal effects of motor development on sibling relationships. Overall, the suggestion that older siblings may provide a good model of motor skills for infants is not supported by the current data. In the future it will be important to assess the dynamic interactions between different factors in predicting infant motor development, allowing early identification of motor difficulties, which could impact other areas of cognitive development and health
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