There is increasing interest in the potential contribution of the gut microbiome to autism spectrum disorder (ASD). However, previous studies have been underpowered and have not been designed to ...address potential confounding factors in a comprehensive way. We performed a large autism stool metagenomics study (n = 247) based on participants from the Australian Autism Biobank and the Queensland Twin Adolescent Brain project. We found negligible direct associations between ASD diagnosis and the gut microbiome. Instead, our data support a model whereby ASD-related restricted interests are associated with less-diverse diet, and in turn reduced microbial taxonomic diversity and looser stool consistency. In contrast to ASD diagnosis, our dataset was well powered to detect microbiome associations with traits such as age, dietary intake, and stool consistency. Overall, microbiome differences in ASD may reflect dietary preferences that relate to diagnostic features, and we caution against claims that the microbiome has a driving role in ASD.
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•Limited autism-microbiome associations from stool metagenomics of n = 247 children•Romboutsia timonensis was the only taxa associated with autism diagnosis•Autistic traits such as restricted interests are associated with less-diverse diet•Less-diverse diet, in turn, is associated with lower microbiome alpha-diversity
Large autism stool metagenomics study finds limited direct autism associations, in contrast to strong relationships with dietary traits, stool consistency, and age, suggestive of a model whereby genetic and phenotypic measures of the autism spectrum promote a less-diverse diet that reduces microbiome diversity.
Autism omics research has historically been reductionist and diagnosis centric, with little attention paid to common co-occurring conditions (for example, sleep and feeding disorders) and the complex ...interplay between molecular profiles and neurodevelopment, genetics, environmental factors and health. Here we explored the plasma lipidome (783 lipid species) in 765 children (485 diagnosed with autism spectrum disorder (ASD)) within the Australian Autism Biobank. We identified lipids associated with ASD diagnosis (n = 8), sleep disturbances (n = 20) and cognitive function (n = 8) and found that long-chain polyunsaturated fatty acids may causally contribute to sleep disturbances mediated by the FADS gene cluster. We explored the interplay of environmental factors with neurodevelopment and the lipidome, finding that sleep disturbances and unhealthy diet have a convergent lipidome profile (with potential mediation by the microbiome) that is also independently associated with poorer adaptive function. In contrast, ASD lipidome differences were accounted for by dietary differences and sleep disturbances. We identified a large chr19p13.2 copy number variant genetic deletion spanning the LDLR gene and two high-confidence ASD genes (ELAVL3 and SMARCA4) in one child with an ASD diagnosis and widespread low-density lipoprotein-related lipidome derangements. Lipidomics captures the complexity of neurodevelopment, as well as the biological effects of conditions that commonly affect quality of life among autistic people.
Autism spectrum disorder (ASD) is a complex neurodevelopmental condition whose biological basis is yet to be elucidated. The Australian Autism Biobank (AAB) is an initiative of the Cooperative ...Research Centre for Living with Autism (Autism CRC) to establish an Australian resource of biospecimens, phenotypes and genomic data for research on autism.
Genome-wide single-nucleotide polymorphism genotypes were available for 2,477 individuals (after quality control) from 546 families (436 complete), including 886 participants aged 2 to 17 years with diagnosed (n = 871) or suspected (n = 15) ASD, 218 siblings without ASD, 1,256 parents, and 117 unrelated children without an ASD diagnosis. The genetic data were used to confirm familial relationships and assign ancestry, which was majority European (n = 1,964 European individuals). We generated polygenic scores (PGS) for ASD, IQ, chronotype and height in the subset of Europeans, and in 3,490 unrelated ancestry-matched participants from the UK Biobank. We tested for group differences for each PGS, and performed prediction analyses for related phenotypes in the AAB. We called copy-number variants (CNVs) in all participants, and intersected these with high-confidence ASD- and intellectual disability (ID)-associated CNVs and genes from the public domain.
The ASD (p = 6.1e-13), sibling (p = 4.9e-3) and unrelated (p = 3.0e-3) groups had significantly higher ASD PGS than UK Biobank controls, whereas this was not the case for height-a control trait. The IQ PGS was a significant predictor of measured IQ in undiagnosed children (r = 0.24, p = 2.1e-3) and parents (r = 0.17, p = 8.0e-7; 4.0% of variance), but not the ASD group. Chronotype PGS predicted sleep disturbances within the ASD group (r = 0.13, p = 1.9e-3; 1.3% of variance). In the CNV analysis, we identified 13 individuals with CNVs overlapping ASD/ID-associated CNVs, and 12 with CNVs overlapping ASD/ID/developmental delay-associated genes identified on the basis of de novo variants.
This dataset is modest in size, and the publicly-available genome-wide-association-study (GWAS) summary statistics used to calculate PGS for ASD and other traits are relatively underpowered.
We report on common genetic variation and rare CNVs within the AAB. Prediction analyses using currently available GWAS summary statistics are largely consistent with expected relationships based on published studies. As the size of publicly-available GWAS summary statistics grows, the phenotypic depth of the AAB dataset will provide many opportunities for analyses of autism profiles and co-occurring conditions, including when integrated with other omics datasets generated from AAB biospecimens (blood, urine, stool, hair).
Mild traumatic brain injury (mTBI, or concussion), results from direct and indirect trauma to the head (i.e. a closed injury of transmitted forces), with or without loss of consciousness. The current ...method of diagnosis is largely based on symptom assessment and clinical history. There is an urgent need to identify an objective biomarker which can not only detect injury, but inform prognosis and recovery. Ocular motor impairment is argued to be ubiquitous across mTBI subtypes and may serve as a valuable clinical biomarker with the recent advent of more affordable and portable eye tracking technology. Many groups have positively correlated the degree of ocular motor impairment to symptom severity with a minority attempting to validate these findings with diffusion tract imaging and functional MRI. However, numerous methodological issues limit the interpretation of results, preventing any singular ocular biomarker from prevailing. This review will comprehensively describe the anatomical susceptibility, clinical measurement, and current eye tracking literature surrounding saccades, smooth pursuit, vestibulo-ocular reflex, vergence, pupillary light reflex, and accommodation in mTBI.
Mild traumatic brain injury (mTBI), commonly known as concussion, is a complex neurobehavioral phenomenon affecting six in 1000 people globally each year. Symptoms last between days and years as ...microstructural damage to axons and neurometabolic changes result in brain network disruption. There is no clinically available objective biomarker to diagnose the severity of injury or monitor recovery. However, emerging evidence suggests eye movement dysfunction (e.g., saccades and smooth pursuits) in patients with mTBI. Patients with a higher symptom burden and prolonged recovery time following injury may show higher degrees of eye movement dysfunction. Likewise, recent advances in magnetic resonance imaging (MRI) have revealed both white matter tract damage and functional network alterations in mTBI patients, which involve areas responsible for the ocular motor control. This scoping review is presented in three sections: Section 1 explores the anatomical control of eye movements to aid the reader with interpreting the discussion in subsequent sections. Section 2 examines the relationship between abnormal MRI findings and eye tracking after mTBI based on the available evidence. Finally, Section 3 communicates gaps in our knowledge about MRI and eye tracking, which should be addressed in order to substantiate this emerging field.
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This review aims to scientifically resolve the correlation between eye movement dysfunction in mTBI with advanced neuroimaging. Included are the neuroanatomical basis of eye movement control, novel MRI correlations to eye tracking measures in mTBI patients, and areas requiring future research.
Mild traumatic brain injury (mTBI), also known as concussion, is a common injury which affects patients of all demographics. There is a global effort to accurately diagnose and identify patients at ...highest risk of prolonged symptom burden to facilitate appropriate rehabilitation efforts. Underreporting is common with large numbers not engaging with services, in addition to differences in treatment outcomes according to ethnicity, age, and gender. As patients recover, symptomology evolves which challenges rehabilitative efforts with no clear definition of ‘recovered’. This review describes key areas in mTBI such as diagnostic challenges, epidemiology, prognosis, and pathophysiology which serves as an introduction to “Eye Movements in Mild Traumatic Brain Injury: Ocular Biomarkers.”
Stigma has been identified as a major barrier to help-seeking, treatment and recovery from gambling problems. However, little research has attempted to examine in any depth the causes, ...characteristics and consequences of stigma in relation to people experiencing gambling problems. The effects of stigma on people experiencing gambling problems, although not directly examined, are apparent through low rates of problem disclosure and treatment-seeking. In this paper, we aim to inform research into stigma associated with problem gambling by highlighting gaps in existing research and by providing direction for future research. The contribution of this paper is that for the first time stigma and problem gambling are drawn together and reviewed using broad constructs and literature from a range of seminal and new sources to present a synthesis of new and important information on stigma. In regard to problem gambling, the dimensions of stigma, except for origin, have yet to be investigated, as well as the processes of stigma creation, the characteristics of public and felt stigma, and coping strategies used to manage stigma. The practical implications of this review are summarized in a framework provided to inform future research into stigma related to problem gambling.
Abstract
Background
Iron deficiency has deleterious effects in patients with cardiopulmonary disease, independent of anemia. Low ferritin has been associated with increased mortality in patients ...undergoing cardiac surgery, but modern indices of iron deficiency need to be explored in this population.
Methods
We conducted a retrospective single-centre observational study of 250 adults in a UK academic tertiary hospital undergoing median sternotomy for non-emergent isolated aortic valve replacement. We characterised preoperative iron status using measurement of both plasma ferritin and soluble transferrin receptor (sTfR), and examined associations with clinical outcomes.
Results
Measurement of plasma sTfR gave a prevalence of iron deficiency of 22%. Patients with non-anemic iron deficiency had clinically significant prolongation of total hospital stay (mean increase 2.2 days; 95% CI: 0.5–3.9;
P
= 0.011) and stay within the cardiac intensive care unit (mean increase 1.3 days; 95% CI: 0.1–2.5;
P
= 0.039). There were no deaths. Defining iron deficiency as a plasma ferritin < 100 µg/L identified 60% of patients as iron deficient and did not predict length of stay. No significant associations with transfusion requirements were evident using either definition of iron deficiency.
Conclusions
These findings indicate that when defined using sTfR rather than ferritin, non-anemic iron deficiency predicts prolonged hospitalisation following surgical aortic valve replacement. Further studies are required to clarify the role of contemporary laboratory indices in the identification of preoperative iron deficiency in patients undergoing cardiac surgery. An interventional study of intravenous iron targeted at preoperative non-anemic iron deficiency is warranted.
Failure to recognise and respond to patient deterioration on hospital wards is a common cause of healthcare-related harm. If patients are not rescued and suffer a cardiac arrest as a result then only ...around 15% will survive. Track and Trigger systems have been introduced into the NHS to improve both identification and response to such patients. This study examines the association between the type of Track & Trigger System (TTS) (National Early Warning Score (NEWS) versus non-NEWS) and the mode of TTS (paper TTS versus electronic TTS) and incidence of in-hospital ward-based cardiac arrests (IHCA) attended by a resuscitation team.
TTS type and mode was retrospectively collected at hospital level from 106 NHS acute hospitals in England between 2009 to 2015 via an organisational survey. Poisson regression and logistic regression models, adjusted for case-mix, temporal trends and seasonality were used to determine the association between TTS and hospital-level ward-based IHCA and survival rates.
The NEWS was introduced in England in 2012 and by 2015, three-fifths of hospitals had adopted it. One fifth of hospitals had instituted an electronic TTS by 2015. Between 2009 and 2015 the incidence of IHCA fell. Introduction or use of NEWS in a hospital was associated with a reduction of 9.4% in the rate of ward-based IHCA compared to non-NEWS systems (incidence rate ratio 0.906, p < 0.001). The use of an electronic TTS was also associated with a reduction of 9.8% in the rate of IHCA compared with paper-based TTS (incidence rate ratio 0.902, p = 0.009). There was no change in hospital survival.
The introduction of standardised TTS and electronic TTS have the potential to reduce ward-based IHCA. This is likely to be via a range of mechanisms from early intervention to institution of treatment limits. The lack of association with survival may reflect the complexity of response to triggering of the afferent arm of the rapid response system.
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