scholarly journals Untargeted metabolomic study of autism in newborn screening samples: a pilot study

2020 ◽  
Author(s):  
Julie Courraud ◽  
Madeleine Ernst ◽  
Susan Svane Laursen ◽  
David M. Hougaard ◽  
Arieh S. Cohen
Keyword(s):  
Newborn Screening ◽  
Autism Spectrum ◽  
Spectral Features ◽  
Pilot Studies ◽  
Metabolic Markers ◽  
Structure Information ◽  
Mass Spectral ◽  
Principal Coordinates ◽  
Chemical Profiles ◽  
Metabolomic Study

AbstractBackgroundThe etiopathology of autism spectrum disorder (ASD) is unclear. Main risk factors include both genetic and non-genetic factors, especially prenatal and perinatal events. The Danish Neonatal Screening Biobank in connection with registry data provides unique opportunities to study early signs of disease. Therefore, we aimed to study the metabolomic profiles of dried blood spot (DBS) of newborns later diagnosed with ASD.MethodsFrom the iPsych cohort, we randomly selected 37 subjects born in 2005 and diagnosed with ASD in 2012 (cases) together with 37 matched controls and submitted their biobanked DBS to an LC-MS/MS-based untargeted metabolomics protocol. Raw data were preprocessed using MZmine 2.41.2 and metabolites were subsequently putatively annotated using mzCloud, GNPS feature-based molecular networking and other metabolome mining tools (MolNetEnhancer). Statistical analyses and data visualization included principal coordinates analyses, PERMANOVAs, t-tests, and fold-change analyses.Results4360 mass spectral features were detected, of which 150 could be putatively annotated at a high confidence level. Chemical structure information at a broad level could be retrieved for a total of 1009 metabolites, covering 31 chemical classes including bile acids, various lipids, nucleotides, amino acids, acylcarnitines and steroids. Although the untargeted analysis revealed no clear distinction between cases and controls, 18 compounds repeatedly reported in the ASD literature could be detected in our study and three mass spectral features were found differentially abundant in cases and controls before FDR correction. In addition, our results pinpointed important other factors influencing chemical profiles of newborn DBS samples such as gestational age, age at sampling and month of birth.LimitationsInherent to pilot studies, our sample size was insufficient to reveal metabolic markers of ASD. Nevertheless, we were able to establish an efficient metabolomic data acquisition and analysis pipeline and flag main confounders to be considered in future studies.ConclusionsIn this first untargeted DBS metabolomic study, newborns later diagnosed with ASD did not show a significantly different metabolic profile when compared to controls. Nevertheless, our method covered many metabolites associated with ASD in previous studies, suggesting that biochemical markers of ASD are present at birth and may be monitored during newborn screening.

scholarly journals Studying Autism Using Untargeted Metabolomics in Newborn Screening Samples

2021 ◽  
Author(s):  
Julie Courraud ◽  
Madeleine Ernst ◽  
Susan Svane Laursen ◽  
David M. Hougaard ◽  
Arieh S. Cohen
Keyword(s):  
Newborn Screening ◽  
Biochemical Markers ◽  
Chemical Structure ◽  
Autism Spectrum ◽  
Untargeted Metabolomics ◽  
Future Studies ◽  
Structure Information ◽  
Mass Spectral ◽  
Feature Based ◽  
Broad Level

AbstractMain risk factors of autism spectrum disorder (ASD) include both genetic and non-genetic factors, especially prenatal and perinatal events. Newborn screening dried blood spot (DBS) samples have great potential for the study of early biochemical markers of disease. To study DBS strengths and limitations in the context of ASD research, we analyzed the metabolomic profiles of newborns later diagnosed with ASD. We performed LC-MS/MS-based untargeted metabolomics on DBS from 37 case-control pairs randomly selected from the iPSYCH sample. After preprocessing using MZmine 2.41, metabolites were putatively annotated using mzCloud, GNPS feature-based molecular networking, and MolNetEnhancer. A total of 4360 mass spectral features were detected, of which 150 (113 unique) could be putatively annotated at a high confidence level. Chemical structure information at a broad level could be retrieved for 1009 metabolites, covering 31 chemical classes. Although no clear distinction between cases and controls was revealed, our method covered many metabolites previously associated with ASD, suggesting that biochemical markers of ASD are present at birth and may be monitored during newborn screening. Additionally, we observed that gestational age, age at sampling, and month of birth influence the metabolomic profiles of newborn DBS, which informs us on the important confounders to address in future studies.

Assessment and treatment of anxiety in children and adolescents with ASD: a systematic review

2021 ◽  
Vol ahead-of-print (ahead-of-print) ◽  
Author(s):  
Celal Perihan ◽  
Mack D. Burke ◽  
Lisa Bowman-Perrott ◽  
Joel Bocanegra
Keyword(s):  
Systematic Review ◽  
Empirical Evidence ◽  
Implementation Fidelity ◽  
Autism Spectrum ◽  
Anxiety Symptoms ◽  
Typically Developing ◽  
Typically Developing Children ◽  
Pilot Studies ◽  
Content Type ◽  
Children With Asd

Purpose The purpose of this study was to investigate the quality of current studies that assess and treat anxiety symptoms in children with autism spectrum disorder (ASD). More specifically the study aimed to answer the following questions: What are the qualities of the current studies using cognitive behavioral therapies (CBTs) to treat anxiety symptoms in children with ASD? Did studies make necessary modifications and adaptations to CBTs according to the evidence-based strategies and implement these versions of CBTs with precise fidelity? Were the selected measurements appropriate for assessing the anxiety symptoms in children with ASD? Design/methodology/approach A systematic review protocol was developed from the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (Moher et al., 2009). A rubric was adapted based on the CEC (Council for Exceptional Children; Cook, 2014) group comparison studies standards and the Evaluative Method for Determining EBP in Autism (Reichow et al., 2007). The 3-point Likert Scale (Chard et al., 2009) was adapted to score each study based on the rubric. Findings CBT is a first-line treatment with significant mixed results. Current studies use adapted versions of existing CBTs for children with ASD without reporting empirical evidence to these adaptations and changes. Reporting of the implementation fidelity is still an issue in the treatment of anxiety. Anxiety measurements that were designed for typically developing children failure to detect unusual anxiety symptoms in children with ASD. Research limitations/implications The first limitation of this study was including a variety of studies across CBT programs and types of anxiety symptoms. Types of anxiety and CBT treatments may require separate analyses with specific indicators. Due to the limited studies, reviews could not be analyzed across types of CBT programs. The second limitation was the types of studies. Most of the studies were pilot studies. Pilot studies might use various instruments and CBTs components for making selections to produce the best effects and results. The final limitation was the lack of examination of the data analysis process. Originality/value These findings are important because due to the variety of changes or adaptation to CBTs, inappropriate implementations and failure to detect unusual anxiety symptoms of children with ASD may cause significant differences in treatment responses and outcomes. The study demonstrated that the majority of the studies used adapted versions of existing CBTs without reporting empirical evidence for these adaptations and changes. The findings have shown that reporting of the implementation fidelity is still an issue. Moreover, the majority of studies had used anxiety measurements that were designed for typically developing children, not for children with ASD.

scholarly journals Neonatal Screening for MPS Disorders in Latin America: A Survey of Pilot Initiatives

2020 ◽  
Vol 6 (4) ◽  
pp. 90
Author(s):  
Francyne Kubaski ◽  
Inês Sousa ◽  
Tatiana Amorim ◽  
Danilo Pereira ◽  
Joe Trometer ◽  
...  
Keyword(s):  
Latin America ◽  
Newborn Screening ◽  
Treatment Options ◽  
Digital Microfluidics ◽  
Premature Death ◽  
Lysosomal Storage ◽  
Pilot Studies ◽  
The Usa ◽  
History Of ◽  
Mps I

Newborn screening enables the diagnosis of treatable disorders at the early stages, and because of its countless benefits, conditions have been continuously added to screening panels, allowing early intervention, aiming for the prevention of irreversible manifestations and even premature death. Mucopolysaccharidoses (MPS) are lysosomal storage disorders than can benefit from an early diagnosis, and thus are being recommended for newborn screening. They are multisystemic progressive disorders, with treatment options already available for several MPS types. MPS I was the first MPS disorder enrolled in the newborn screening (NBS) panel in the USA and a few other countries, and other MPS types are expected to be added. Very few studies about NBS for MPS in Latin America have been published so far. In this review, we report the results of pilot studies performed in Mexico and Brazil using different methodologies: tandem mass spectrometry, molecular analysis, digital microfluidics, and fluorimetry. These experiences are important to report and discuss, as we expect to have several MPS types added to NBS panels shortly. This addition will enable timely diagnosis of MPS, avoiding the long diagnostic odyssey that is part of the current natural history of this group of diseases, and leading to a better outcome for the affected patients.

scholarly journals Mass spectral characterization of primary emissions and implications in source apportionment of organic aerosol

2020 ◽  
Vol 13 (6) ◽  
pp. 3205-3219 ◽  
Author(s):  
Weiqi Xu ◽  
Yao He ◽  
Yanmei Qiu ◽  
Chun Chen ◽  
Conghui Xie ◽  
...  
Keyword(s):  
Source Apportionment ◽  
Spectral Characteristics ◽  
Organic Aerosol ◽  
Water Soluble ◽  
Spectral Characterization ◽  
Rural Site ◽  
Spectral Features ◽  
Mass Spectral ◽  
Spectral Profiles ◽  
Primary Emissions

Abstract. Source apportionment of organic aerosol (OA) from aerosol mass spectrometer (AMS) or aerosol chemical speciation monitor (ACSM) measurements relies largely upon mass spectral profiles from different source emissions. However, the changes in mass spectra of primary emissions from AMS–ACSM with the newly developed capture vaporizer (CV) are poorly understood. Here we conducted 21 cooking, crop straw, wood, and coal burning experiments to characterize the mass spectral features of OA and water-soluble OA (WSOA) using SV-AMS and CV-ACSM. Our results show overall similar spectral characteristics between SV-AMS and CV-ACSM for different primary emissions despite additional thermal decomposition in CV, and the previous spectral features for diagnostics of primary OA factors are generally well retained. However, the mass spectral differences between OA and WSOA can be substantial for both SV-AMS and CV-ACSM. The changes in f55 (fraction of m∕z 55 in OA) vs. f57, f44 vs. f60, and f44 vs. f43 in CV-ACSM are also observed, yet the evolving trends are similar to those of SV-AMS. By applying the source spectral profiles to a winter CV-ACSM study at a highly polluted rural site in the North China Plain, the source apportionment of primary OA was much improved, highlighting the two most important primary sources of biomass burning and coal combustion (32 % and 21 %). Considering the rapidly increasing deployments of CV-ACSM and WSOA studies worldwide, the mass spectral characterization has significant implications by providing essential constraints for more accurate source apportionment and making better strategies for air pollution control in regions with diverse primary emissions.

scholarly journals Application of protein set enrichment analysis to correlation of protein functional sets with mass spectral features and multivariate proteomic tests

2020 ◽  
Vol 15 ◽  
pp. 44-53 ◽  
Author(s):  
Julia Grigorieva ◽  
Senait Asmellash ◽  
Carlos Oliveira ◽  
Heinrich Roder ◽  
Lelia Net ◽  
...  
Keyword(s):  
Enrichment Analysis ◽  
Spectral Features ◽  
Mass Spectral

scholarly journals Social Interaction Improved by Oxytocin in the Subclass of Autism with Comorbid Intellectual Disabilities

Diseases ◽  
2019 ◽  
Vol 7 (1) ◽  
pp. 24 ◽  
Author(s):  
Haruhiro Higashida ◽  
Toshio Munesue ◽  
Hirotaka Kosaka ◽  
Hidenori Yamasue ◽  
Shigeru Yokoyama ◽  
...  
Keyword(s):  
Social Interaction ◽  
Adverse Effects ◽  
Intellectual Disabilities ◽  
Autism Spectrum ◽  
Pilot Studies ◽  
Therapeutic Benefits ◽  
Adolescents And Adults ◽  
History Of ◽  
History Of Epilepsy ◽  
Adults With Asd

Approximately half of all autism spectrum disorder (ASD) individuals suffer from comorbid intellectual disabilities. Furthermore, the prevalence of epilepsy has been estimated to be 46% of patients with low intelligence quotient. It is important to investigate the therapeutic benefits and adverse effects of any recently developed drugs for this proportion of individuals with the so-called Kanner type of ASD. Therefore, we investigated the therapeutic and/or adverse effects of intranasal oxytocin (OT) administration, especially in adolescents and adults with ASD and comorbid intellectual disability and epilepsy, with regard to core symptoms of social deficits. We have already reported three randomized placebo-controlled trials (RCTs). However, we revisit results in our pilot studies from the view of comorbidity. Most of the intellectually disabled participants were found to be feasible participants of the RCT. We observed significantly more events regarded as reciprocal social interaction in the OT group compared with the placebo group. In the trial, no or little differences in adverse events were found between the OT and placebo arms, as found in some other reports. However, seizures were induced in three participants with medical history of epilepsy during or after OT treatment. In conclusion, we stress that behavioral changes in ASD patients with intellectual disabilities could be recognized not by the conventional measurements of ASD symptoms but by detailed evaluation of social interactions arising in daily-life situations.

scholarly journals Early Identification of Fragile X Syndrome through Expanded Newborn Screening

2019 ◽  
Vol 9 (1) ◽  
pp. 4 ◽  
Author(s):  
Katherine C. Okoniewski ◽  
Anne C. Wheeler ◽  
Stacey Lee ◽  
Beth Boyea ◽  
Melissa Raspa ◽  
...  
Keyword(s):  
North Carolina ◽  
Newborn Screening ◽  
Fragile X Syndrome ◽  
Fragile X ◽  
Pilot Studies ◽  
The Past ◽  
Innovative Program ◽  
Expanded Newborn Screening ◽  
Age Of Diagnosis

Over the past 20 years, research on fragile X syndrome (FXS) has provided foundational understanding of the complex experiences of affected individuals and their families. Despite this intensive focus, there has been little progress on earlier identification, with the average age of diagnosis being 3 years. For intervention and treatment approaches to have the greatest impact, they need to begin shortly after birth. To access this critical timespan, differential methods of earlier identification need to be considered, with an emerging focus on newborn screening practices. Currently, barriers exist that prevent the inclusion of FXS on standard newborn screening panels. To address these barriers, an innovative program is being implemented in North Carolina to offer voluntary screening for FXS under a research protocol, called Early Check. This program addresses the difficulties observed in prior pilot studies, such as recruitment, enrollment, lab testing, and follow-up. Early Check provides an opportunity for stakeholders and the research community to continue to gain valuable information about the feasibility and greater impact of newborn screening on the FXS population.

scholarly journals Analysis of Apple Flavours: The Use of Volatile Organic Compounds to Address Cultivar Differences and the Correlation between Consumer Appreciation and Aroma Profiling

2020 ◽  
Vol 2020 ◽  
pp. 1-7
Author(s):  
Gareth Roberts ◽  
Natasha D. Spadafora
Keyword(s):  
Volatile Organic Compounds ◽  
Organic Compounds ◽  
Cultivar Differences ◽  
Gas Chromatography Mass Spectrometry ◽  
Mass Spectral ◽  
Random Forest Classification ◽  
Forest Classification ◽  
Principal Coordinates ◽  
Volatile Organic ◽  
Processing And Storage

In the selection of apple (Malus domestica Borkh) fruits, consumers predominantly use visual and organoleptic responses, such as aroma and texture, as quality/preference markers. Previous studies profiling the sensory properties and aroma profiles of apple varieties have provided a lexicon describing important attributes within the modalities of aroma, texture, and flavour. The range of volatile organic compounds (VOCs) produced by four apple cultivars was assessed by thermal desorption-gas chromatography-mass spectrometry (TD-GC-MS). To facilitate automated dynamic headspace extraction of the VOCs from bulk samples, a small multichamber thermal extraction system was used. Forty compounds were detected and putatively identified by mass spectral comparison with NIST libraries. Eight compounds were not previously identified in apples. Permutational multivariate analysis of variance (PerMANOVA) and canonical analysis of principal coordinates (CAP) done on the whole volatile organic compound profiles show separation of the four cultivars. The use of random forest classification enabled the determination of a minimum set of fifteen potential VOC markers that successfully differentiate the cultivars under study. Trends across samples, VOCs, and sensory evaluation are revealed. The association between 4-hexen-1-ol acetate with texture/consistency, and crispiness, and correlation of 2-methylbut-2-en-1-yl acetate with juiciness and acidity is shown for the first time. These sensory correlations indicate that the compounds determined by this experiment could be used as objective markers for the consumer appreciation of fresh apples, enabling the optimum conditions for processing and storage of individual cultivars to be identified without recourse to expensive sensory panels in every case. Such tests could also be used as part of routine quality control by the producer and retailer, reducing costs and eliminating waste due to batches of inferior product.

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