Development of a Self-Report Measure of Prediction in Daily Life: The Prediction-Related Experiences Questionnaire.

PURPOSE: Predictions are complex, multisensory, and dynamic processes involving real-time adjustments based on environmental inputs. Disruptions to prediction abilities have been proposed to underlie characteristics associated with autism. While there is substantial empirical literature related to prediction, the field lacks a self-assessment measure of prediction skills related to daily tasks. Such a measure would be useful to better understand the nature of day-to-day prediction-related activities and characterize these abilities in individuals who struggle with prediction. METHODS: An interdisciplinary mixed-methods approach was utilized to develop and validate a self-report questionnaire of prediction skills for adults, the Prediction-Related Experiences Questionnaire (PRE-Q). Two rounds of online field testing were completed in samples of autistic and neurotypical (NT) adults. Qualitative feedback from a subset of these participants regarding question content and quality was integrated and Rasch modeling of the item responses was applied. RESULTS: The final PRE-Q includes 19 items across 3 domains (Sensory, Motor, Social), with evidence supporting the validity of the measure's 4-point response categories, internal structure, and relationship to other outcome measures associated with prediction. Consistent with models of prediction challenges in autism, autistic participants indicated more prediction-related difficulties than the NT group. CONCLUSIONS: This study provides evidence for the validity of a novel self-report questionnaire designed to measure the day-to-day prediction skills of autistic and non-autistic adults. Future research should focus on characterizing the relationship between the PRE-Q and lab-based measures of prediction, and understanding how the PRE-Q may be used to identify potential areas for clinical supports for individuals with prediction-related challenges.

Retinopathy of prematurity and neurodevelopmental outcome and quality of life at 10 years of age.

Objective: In a cohort of 10-year-old children born extremely preterm, we evaluated the hypothesis that increasing severity of retinopathy of prematurity (ROP) is associated with increasing frequency of unfavorable neurodevelopmental and quality of life outcomes. Study Design: Study participants were classified according to the severity of ROP. At 10 years of age, their neurocognitive abilities, academic achievement, and gross motor function were assessed, and they were evaluated for autism spectrum disorder, anxiety, depression, and quality of life. Results: After adjustment for sample attrition and confounders, only the association with lower quality of life persisted. Increasing severity of visual impairment was associated with worse neurodevelopmental outcomes and lower quality of life. Conclusion: Among extremely preterm children, severity of visual impairment, but not severity of ROP, was associated with adverse neurodevelopmental outcomes at 10 years of age. Both severe ROP and more severe visual impairment were associated with lower quality of life.

Reproducibility between preschool and school-age Social Responsiveness Scale forms in the Environmental influences on Child Health Outcomes program.

Evidence suggests core autism trait consistency in older children, but development of these traits is variable in early childhood. The Social Responsiveness Scale (SRS) measures autism-related traits and broader autism phenotype, with two age-dependent forms in childhood (preschool, 2.5-4.5 years; school age, 4-18 years). Score consistency has been observed within forms, though reliability across forms has not been evaluated. Using data from the Environmental Influences on Child Health Outcomes (ECHO) program (n = 853), preschool, and school-age SRS scores were collected via maternal report when children were an average of 3.0 and 5.8 years, respectively. We compared reproducibility of SRS total scores (T-scores) and agreement above a clinically meaningful cutoff (T-scores ≥ 60) and examined predictors of discordance in cutoff scores across forms. Participant scores across forms were similar (mean difference: 3.3 points; standard deviation: 7), though preschool scores were on average lower than school-age scores. Most children (88%) were classified below the cutoff on both forms, and overall concordance was high (92%). However, discordance was higher in cohorts following younger siblings of autistic children (16%). Proportions of children with an autism diagnoses were also higher among those with discordant scores (27%) than among those with concordant scores (4%). Our findings indicate SRS scores are broadly reproducible across preschool and school-age forms, particularly for capturing broader, nonclinical traits, but also suggest that greater variability of autism-related traits in preschool-age children may reduce reliability with later school-age scores for those in the clinical range.

Cerebral Palsy and Motor Impairment After Extreme Prematurity: Prediction of Diagnoses at Ages 2 and 10 Years.

OBJECTIVE: To identify perinatal factors in children born extremely preterm (EP) that were associated with motor impairment (MI) at 2 and 10 years of age and develop a predictive algorithm to estimate the risk of MI during childhood. STUDY DESIGN: Participants of the Extremely Low Gestational Age Newborns Study (ELGANS) were classified as: no MI, MI only at 2 years, MI only at 10 years, and MI at both 2 and 10 years, based on a standardized neurological examination at 2 and the Gross Motor Function Classification System (GMFCS) at 10 years of age. Least Absolute Shrinkage and Selection Operator (LASSO) regression was used to develop the final predictive model. RESULTS: Of the 849 study participants, 64 (7.5%) had a diagnosis of MI at both 2 and 10 years and 63 (7.4%) had a diagnosis of MI at 1 visit but not the other. Of 22 total risk factors queried, 4 variables most reliably and accurately predicted MI: gestational age, weight z-score growth trajectory during neonatal intensive care unit (NICU) stay, ventriculomegaly, and cerebral echolucency on head ultrasound. By selecting probability thresholds of 3.5% and 7.0% at ages 2 and 10, respectively, likelihood of developing MI can be predicted with a sensitivity and specificity of 71.2%/72.1% at age 2 and 70.7%/70.7% at age 10. CONCLUSION: In our cohort, the diagnosis of MI at 2 years did not always predict a diagnosis of MI at 10 years. Specific risk factors are predictive of MI and can estimate an individual infant's risk at NICU discharge of MI at age 10 years.

Association of Growth During Infancy with Neurodevelopment and Obesity in Children Born Very Preterm: The Environmental Influences on Child Health Outcomes Cohort.

OBJECTIVE: To evaluate associations between change in weight z score after neonatal intensive care unit (NICU) discharge and neurodevelopmental outcomes and obesity at 12-48 months of age among individuals born very preterm. STUDY DESIGN: This secondary analysis used data from infants born very preterm participating in the Environmental influences on Child Health Outcomes cohort (n = 1400). Growth during infancy was calculated as change in weight z score between NICU discharge and follow-up at a mean of 27 months of age. Very low weight gain was defined as a change in weight z score <-1.67; very high weight gain was a change in weight z score >1.67. Neurodevelopmental outcomes included the Bayley Scales of Infant and Toddler Development, Child Behavior Checklist 1.5-5 years, and Modified Checklist for Autism in Toddlers. Multivariable linear regression was used to estimate associations between increase in weight z score and neurodevelopmental outcomes. RESULTS: Very low weight gain between NICU discharge and follow-up (experienced by 6.4% of participants) was associated with lower scores on cognitive (adjusted mean difference: -4.26; 95% CI: -8.55, -0.04) and language (adjusted mean difference: -4.80; 95% CI: -9.70, -0.11) assessments. Very high weight gain (experienced by 13.6% of participants) was associated with an increased obesity risk (adjusted relative risk: 6.20; 95% CI: 3.99, 9.66) but not with neurodevelopmental outcomes. CONCLUSIONS: Very high weight gain in the first 12-48 months after NICU discharge was associated with a higher risk of obesity at follow-up; very low weight gain was associated with lower scores on cognitive and language assessments.

Developmental characteristics and accuracy of autism screening among two-year-old toddlers in the ECHO program.

BACKGROUND: The Modified Checklist for Autism in Toddlers (M-CHAT) is a common pediatric screening tool with mixed accuracy findings. Prior evidence supports M-CHAT screening for developmental concerns, especially in toddlers born preterm. This study examined M-CHAT accuracy in a large, nationwide sample. METHODS: 3393 participants from the Environmental influences on Child Health Outcomes (ECHO) program were included. Harmonized M-CHAT (M-CHAT-H) results were compared with parent-reported autism diagnosis and autism-related characteristics to assess accuracy for term and preterm children, together and separately. Generalized estimating equations, clustering for ECHO cohort and controlling for demographic covariates, were used to examine associations between developmental and behavioral characteristics with M-CHAT-H accuracy. RESULTS: Sensitivity of the M-CHAT-H ranged from 36 to 60%; specificity ranged from 88 to 99%. Positive M-CHAT-H was associated with more developmental delays and behavior problems. Children with severe motor delays and more autism-related problems were more likely to have a false-negative M-CHAT-H. Children with fewer behavior problems and fewer autism-related concerns were more likely to have a false-positive screen. CONCLUSION: The M-CHAT-H accurately detects children at low risk for autism and children at increased risk with moderate accuracy. These findings support use of the M-CHAT-H in assessing autism risk and developmental and behavioral concerns in children. IMPACT: Previous literature regarding accuracy of the Modified Checklist for Autism in Toddlers (M-CHAT) is mixed but this study provides evidence that the M-CHAT performs well in detecting children at low risk for autism and consistently detects children with developmental delays and behavioral problems. The M-CHAT moderately detects children at increased risk for autism and remains a useful screening tool. This study examines M-CHAT accuracy in a large-scale, nationwide sample, examining associations between screening accuracy and developmental outcomes. These findings impact pediatric screening for autism, supporting continued use of the M-CHAT while further elucidating the factors associated with inaccurate screens.

Sex Differences in Autistic Youth Born Extremely Preterm.

PURPOSE: To evaluate sex differences in autistic traits in youth born extremely preterm (EP; 23-27 weeks) who were later diagnosed with autism spectrum disorder (ASD) at 10-years. METHOD: A longitudinal cohort design from the Extremely Low Gestational Age Newborn Study (ELGAN) followed N = 857 EP infants from birth through 10-years. EP infants later diagnosed with ASD (N = 61, 20 females) participated in the study. Group differences were evaluated via inferential and Bayesian statistics (values > 1 suggest evidence for alternate hypothesis) on ASD screeners (M-CHAT at 2-years, SCQ and SRS-2 at 10-years), and gold-standard diagnostic measures (ADOS-2, ADI-R) at 10-years. RESULTS: Males scored significantly higher than females on measures of Social Affect from the ADOS-2, t(34.27)=-2.20, BF10 = 2.33, and measures of Repetitive and Restricted Behaviors from the ADI-R, t(40.52)=-2.85, BF10 = 5.26. Bayesian estimates suggested marginal evidence for sex differences in Nonverbal Communication, t(30.66)=-1.81, BF10 = 1.25, and Verbal Communication, t(24.64)=-1.89, BF10 = 1.39, from the ADI-R, wherein males scored higher than females. No statistically significant sex differences were identified on any of the ASD screeners at 2 (M-CHAT) or 10 years (SCQ). No significant sex differences were observed on any subscales of the SRS at 10 years. CONCLUSIONS: EP autistic males present with more autistic traits than EP autistic females on gold-standard diagnostic measures of autism at 10-years of age, despite not presenting with higher autistic traits on screeners at either age. These results align with sex differences observed in full-term, autistic youth. These results suggest ASD screeners may under identify autism in EP youth, particularly females.

Teaching Science to the Next Generation.

Teaching science to the next generation begins with foundations laid in podiatric medical school. Interest and immersion in research continues to develop through residency as trainees prepare for cases, participate in journal clubs, present posters and articles, and attend conferences. Having adequate training is essential to production of quality research. Although challenges and barriers exist, numerous resources are available at all levels of practice to guide those who are interested in contributing to the body of literature that supports the profession. Ensuring a robust pipeline of future clinician scientists is critical to the future of the profession.

Evaluating the Use of Vibrational Spectroscopy to Detect the Level of Adulteration of Cricket Powder in Plant Flours: The Effect of the Matrix.

Edible insects have been recognised as an alternative food or feed ingredient due to their protein value for both humans and domestic animals. The objective of this study was to evaluate the ability of both near- (NIR) and mid-infrared (MIR) spectroscopy to identify and quantify the level of adulteration of cricket powder added into two plant proteins: chickpea and flaxseed meal flour. Cricket flour (CKF) was added to either commercial chickpea (CPF) or flaxseed meal flour (FxMF) at different ratios of 95:5% w/w, 90:10% w/w, 85:15% w/w, 80:20% w/w, 75:25% w/w, 70:30% w/w, 65:35% w/w, 60:40% w/w, or 50:50% w/w. The mixture samples were analysed using an attenuated total reflectance (ATR) MIR instrument and a Fourier transform (FT) NIR instrument. The partial least squares (PLS) cross-validation statistics based on the MIR spectra showed that the coefficient of determination (R2CV) and the standard error in cross-validation (SECV) were 0.94 and 6.68%, 0.91 and 8.04%, and 0.92 and 4.33% for the ALL, CPF vs. CKF, and FxMF vs. CKF mixtures, respectively. The results based on NIR showed that the cross-validation statistics R2CV and SECV were 0.95 and 3.16%, 0.98 and 1.74%, and 0.94 and 3.27% using all the samples analyzed together (ALL), the CPF vs. CKF mixture, and the FxMF vs. CKF mixture, respectively. The results of this study showed the effect of the matrix (type of flour) on the PLS-DA data in both the classification results and the PLS loadings used by the models. The different combination of flours (mixtures) showed differences in the absorbance values at specific wavenumbers in the NIR range that can be used to classify the presence of CKF. Research in this field is valuable in advancing the application of vibrational spectroscopy as routine tools in food analysis and quality control.

Neurodevelopmental and behavioral outcomes of very preterm infants: latent profile analysis in the Environmental influences on Child Health Outcomes (ECHO) Program.

BACKGROUND: Very preterm infants are at high risk for neurodevelopmental impairments. We used a child-centered approach (latent profile analysis [LPA]) to describe 2-year neurobehavioral profiles for very preterm infants based on cognitive, motor, and behavioral outcomes. We hypothesized that distinct outcome profiles would differ in the severity and co-occurrence of neurodevelopmental and behavioral impairment. METHODS: We studied children born <33 weeks' gestation from the Environmental influences on Child Health Outcomes Program with at least one neurobehavioral assessment at age 2 (Bayley Scales of Infant and Toddler Development, Child Behavior Checklist, Modified Checklist for Autism in Toddlers, cerebral palsy diagnosis). We applied LPA to identify subgroups of children with different patterns of outcomes. RESULTS: In 2036 children (52% male; 48% female), we found four distinct neurobehavioral profiles. Most children (~85%) were categorized into one of two profiles characterized by no/mild neurodevelopmental delay and a low prevalence of behavioral problems. Fewer children (~15%) fell into one of two profiles characterized by severe neurodevelopmental impairments. One profile consisted of children (5%) with co-occurring neurodevelopmental impairment and behavioral problems. CONCLUSION: Child-centered approaches provide a comprehensive, parsimonious description of neurodevelopment following preterm birth and can be useful for clinical and research purposes. IMPACT: Most research on outcomes for children born very preterm have reported rates of impairment in single domains. Child-centered approaches describe profiles of children with unique combinations of cognitive, motor, and behavioral strengths and weaknesses. We capitalized on data from the nationwide Environmental influences on Child Health Outcomes Program to examine these profiles in a large sample of children born <33 weeks gestational age. We found four distinct neurobehavioral profiles consisting of different combinations of cognitive, motor, and behavioral characteristics. This information could aid in the development of clinical interventions that target different profiles of children with unique developmental needs.

Tuning the mechanical properties of pectin films with polyphenol-rich plant extracts.

The mechanical properties of pectin films enhanced with polyphenol-rich fruit extracts were investigated. The scavenging and reducing activity of plant extracts incorporated into the pectin films were determined using bench assays, and their antioxidant activity was correlated with a high presence of polyphenols, which were predominantly comprised of flavonoids and anthocyanins. The pectin films generated from the extracts exhibited a range of mechanical properties; tensile strength (4.99 MPa - 6.91 MPa), elongation at break (45.8 % - 52.3 %), and stiffness (1835 g mm-1 - 2765 g mm-1). To investigate the underlying relationships between plant extract composition and mechanical properties, Projection to Latent Structures (PLS) models were developed. The PLS models revealed that extracts containing high sugar and polyphenol content increase the tensile strength and moisture content of films. The elongation at break of the films was improved or diminished depending on the profile of sugar, acids, and polyphenols in the fruit extracts. Furthermore, the structures and concentration of anthocyanins and flavonoids were identified to strongly influenced the elongation at break differences. By modifying the concentration of sugars, organic acids, and polyphenols, the mechanical properties of pectin-based films can be tuned for tailored applications as food packaging materials.

Both stronger and weaker cerebro-cerebellar functional connectivity patterns during processing of spoken sentences in autism spectrum disorder.

Cerebellar differences have long been documented in autism spectrum disorder (ASD), yet the extent to which such differences might impact language processing in ASD remains unknown. To investigate this, we recorded brain activity with magnetoencephalography (MEG) while ASD and age-matched typically developing (TD) children passively processed spoken meaningful English and meaningless Jabberwocky sentences. Using a novel source localization approach that allows higher resolution MEG source localization of cerebellar activity, we found that, unlike TD children, ASD children showed no difference between evoked responses to meaningful versus meaningless sentences in right cerebellar lobule VI. ASD children also had atypically weak functional connectivity in the meaningful versus meaningless speech condition between right cerebellar lobule VI and several left-hemisphere sensorimotor and language regions in later time windows. In contrast, ASD children had atypically strong functional connectivity for in the meaningful versus meaningless speech condition between right cerebellar lobule VI and primary auditory cortical areas in an earlier time window. The atypical functional connectivity patterns in ASD correlated with ASD severity and the ability to inhibit involuntary attention. These findings align with a model where cerebro-cerebellar speech processing mechanisms in ASD are impacted by aberrant stimulus-driven attention, which could result from atypical temporal information and predictions of auditory sensory events by right cerebellar lobule VI.

From private incentives to public health need: rethinking research and development for pandemic preparedness.

Pandemic preparedness and response have relied primarily on market dynamics to drive development and availability of new health products. Building on calls for transformation, we propose a new value proposition that instead prioritises equity from the research and development (R&D) stage and that strengthens capacity to control outbreaks when and where they occur. Key elements include regional R&D hubs free to adapt well established technology platforms, and independent clinical trials networks working with researchers, regulators, and health authorities to better study questions of comparative benefit and real-world efficacy. Realising these changes requires a shift in emphasis: from pandemic response to outbreak control, from one-size-fits-all economies of scale to R&D and manufacture for local need, from de novo product development to last-mile innovation through adaptation of existing technologies, and from proprietary, competitive R&D to open science and financing for the common good that supports collective management and sharing of technology and know-how.

A Comparative Analysis of the Full and Short Versions of the Social Responsiveness Scale in Estimating an Established Autism Risk Factor Association in ECHO: Do we Get the Same Estimates?

PURPOSE: Prior work developed a shortened 16-item version of the Social Responsiveness Scale (SRS), a quantitative measure of social communication and autism spectrum disorder (ASD)-related traits. However, its properties for use in risk factor estimation have not been fully tested compared to the full SRS. We compared the associations between gestational age (previously established risk factor for ASD) and the 65-item "full" and 16-item "short" versions of the SRS to test the shortened version's ability to capture associations in epidemiologic analyses of ASD risk factors. METHODS: We used data from participants in the Environmental influences on Child Health Outcomes (ECHO) Program (n = 2,760). SRS scores were collected via maternal/caregiver report when children were aged 2.5-18 years. We compared estimates of associations between gestational age and preterm birth between the full and short SRS using multivariable linear regression, quantile regression, and prediction methods. RESULTS: Overall, associations based on full and short SRS scores were highly comparable. For example, we observed positive associations between preterm birth with both full ([Formula: see text]=2.8; 95% CI [1.7, 4.0]) and short ([Formula: see text]=2.9; 95% CI [1.6, 4.3]) SRS scores. Quantile regression analyses indicated similar direction and magnitude of associations across the distribution of SRS scores between gestational age with both short and full SRS scores. CONCLUSION: The comparability in estimates obtained for full and short SRS scores with an "established" ASD risk factor suggests ability of the shortened SRS in assessing associations with potential ASD-related risk factors and has implications for large-scale research studies seeking to reduce participant burden.

Reciprocal effects of alpha-synuclein aggregation and lysosomal homeostasis in synucleinopathy models.

BACKGROUND: Lysosomal dysfunction has been implicated in a number of neurodegenerative diseases such as Parkinson's disease (PD). Various molecular, clinical and genetic studies have highlighted a central role of lysosomal pathways and proteins in the pathogenesis of PD. Within PD pathology the synaptic protein alpha-synuclein (αSyn) converts from a soluble monomer to oligomeric structures and insoluble amyloid fibrils. The aim of this study was to unravel the effect of αSyn aggregates on lysosomal turnover, particularly focusing on lysosomal homeostasis and cathepsins. Since these enzymes have been shown to be directly involved in the lysosomal degradation of αSyn, impairment of their enzymatic capacity has extensive consequences. METHODS: We used patient-derived induced pluripotent stem cells and a transgenic mouse model of PD to examine the effect of intracellular αSyn conformers on cell homeostasis and lysosomal function in dopaminergic (DA) neurons by biochemical analyses. RESULTS: We found impaired lysosomal trafficking of cathepsins in patient-derived DA neurons and mouse models with αSyn aggregation, resulting in reduced proteolytic activity of cathepsins in the lysosome. Using a farnesyltransferase inhibitor, which boosts hydrolase transport via activation of the SNARE protein ykt6, we enhanced the maturation and proteolytic activity of cathepsins and thereby decreased αSyn protein levels. CONCLUSIONS: Our findings demonstrate a strong interplay between αSyn aggregation pathways and function of lysosomal cathepsins. It appears that αSyn directly interferes with the enzymatic function of cathepsins, which might lead to a vicious cycle of impaired αSyn degradation. Lysosomal trafficking of cathepsin D (CTSD), CTSL and CTSB is disrupted when alpha-synuclein (αSyn) is aggregated. This results in a decreased proteolytic activity of cathepsins, which directly mediate αSyn clearance. Boosting the transport of the cathepsins to the lysosome increases their activity and thus contributes to efficient αSyn degradation.

Perinatal Factors and Emotional, Cognitive, and Behavioral Dysregulation in Childhood and Adolescence.

OBJECTIVE: This cohort study assessed perinatal factors known to be related to maternal and neonatal inflammation and hypothesized that several would be associated with emotional, cognitive, and behavioral dysregulation in youth. METHOD: The Environmental influences on Child Health Outcomes (ECHO) is a research consortium of 69 pediatric longitudinal cohorts. A subset of 18 cohorts that had both Child Behavior Checklist (CBCL) data on children (6-18 years) and information on perinatal exposures including maternal prenatal infections was used. Children were classified as having the CBCL-Dysregulation Profile (CBCL-DP) if the sum of their T scores for 3 CBCL subscales (attention, anxious/depressed, and aggression) was ≥180. Primary exposures were perinatal factors associated with maternal and/or neonatal inflammation, and associations between these and outcome were assessed. RESULTS: Approximately 13.4% of 4,595 youth met criteria for CBCL-DP. Boys were affected more than girls (15.1% vs 11.5%). More youth with CBCL-DP (35%) were born to mothers with prenatal infections compared with 28% of youth without CBCL-DP. Adjusted odds ratios indicated the following were significantly associated with dysregulation: having a first-degree relative with a psychiatric disorder; being born to a mother with lower educational attainment, who was obese, had any prenatal infection, and/or who smoked tobacco during pregnancy. CONCLUSION: In this large study, a few modifiable maternal risk factors with established roles in inflammation (maternal lower education, obesity, prenatal infections, and smoking) were strongly associated with CBCL-DP and could be targets for interventions to improve behavioral outcomes of offspring. DIVERSITY & INCLUSION STATEMENT: We worked to ensure race, ethnic, and/or other types of diversity in the recruitment of human participants. One or more of the authors of this paper self-identifies as a member of one or more historically underrepresented sexual and/or gender groups in science. We actively worked to promote sex and gender balance in our author group. The author list of this paper includes contributors from the location and/or community where the research was conducted who participated in the data collection, design, analysis, and/or interpretation of the work.

Qualitative Analysis of Polyphenols in Glycerol Plant Extracts Using Untargeted Metabolomics.

Glycerol is a reliable solvent for extracting polyphenols from food and waste products. There has been an increase in the application of glycerol over benchmark alcoholic solvents such as ethanol and methanol for natural product generation because of its non-toxic nature and high extraction efficiency. However, plant extracts containing a high glycerol concentration are unsuitable for mass spectrometry-based investigation utilising electrospray ionization, inhibiting the ability to analyse compounds of interest. In this investigation, a solid phase extraction protocol is outlined for removing glycerol from plant extracts containing a high concentration of glycerol and their subsequent analysis of polyphenols using ultra-performance liquid chromatography coupled with quadrupole time of flight tandem mass spectrometry. Using this method, glycerol-based extracts of Queen Garnet Plum (Prunus salicina) were investigated and compared to ethanolic extracts. Anthocyanins and flavonoids in high abundance were found in both glycerol and ethanol extracts. The polyphenol metabolome of Queen Garnet Plum was 53% polyphenol glycoside derivatives and 47% polyphenols in their aglycone forms. Furthermore, 56% of the flavonoid derivates were found to be flavonoid glycosides, and 44% were flavonoid aglycones. In addition, two flavonoid glycosides not previously found in Queen Garnet Plum were putatively identified: Quercetin-3-O-xyloside and Quercetin-3-O-rhamnoside.

No Differences in Auditory Steady-State Responses in Children with Autism Spectrum Disorder and Typically Developing Children.

Auditory steady-state response (ASSR) has been studied as a potential biomarker for abnormal auditory sensory processing in autism spectrum disorder (ASD), with mixed results. Motivated by prior somatosensory findings of group differences in inter-trial coherence (ITC) between ASD and typically developing (TD) individuals at twice the steady-state stimulation frequency, we examined ASSR at 25 and 50 as well as 43 and 86 Hz in response to 25-Hz and 43-Hz auditory stimuli, respectively, using magnetoencephalography. Data were recorded from 22 ASD and 31 TD children, ages 6-17 years. ITC measures showed prominent ASSRs at the stimulation and double frequencies, without significant group differences. These results do not support ASSR as a robust ASD biomarker of abnormal auditory processing in ASD. Furthermore, the previously observed atypical double-frequency somatosensory response in ASD did not generalize to the auditory modality. Thus, the hypothesis about modality-independent abnormal local connectivity in ASD was not supported.

A multi-omic approach identifies an autism spectrum disorder (ASD) regulatory complex of functional epimutations in placentas from children born preterm.

Children born preterm are at heightened risk of neurodevelopmental impairments, including Autism Spectrum Disorder (ASD). The placenta is a key regulator of neurodevelopmental processes, though the precise underlying molecular mechanisms remain unclear. Here, we employed a multi-omic approach to identify placental transcriptomic and epigenetic modifications related to ASD diagnosis at age 10, among children born preterm. Working with the extremely low gestational age (ELGAN) cohort, we hypothesized that a pro-inflammatory placental environment would be predictive of ASD diagnosis at age 10. Placental messenger RNA (mRNA) expression, CpG methylation, and microRNA (miRNA) expression were compared among 368 ELGANs (28 children diagnosed with ASD and 340 children without ASD). A total of 111 genes displayed expression levels in the placenta that were associated with ASD. Within these ASD-associated genes is an ASD regulatory complex comprising key genes that predicted ASD case status. Genes with expression that predicted ASD case status included Ewing Sarcoma Breakpoint Region 1 (EWSR1) (OR: 6.57 (95% CI: 2.34, 23.58)) and Bromodomain Adjacent To Zinc Finger Domain 2A (BAZ2A) (OR: 0.12 (95% CI: 0.03, 0.35)). Moreover, of the 111 ASD-associated genes, nine (8.1%) displayed associations with CpG methylation levels, while 14 (12.6%) displayed associations with miRNA expression levels. Among these, LRR Binding FLII Interacting Protein 1 (LRRFIP1) was identified as being under the control of both CpG methylation and miRNAs, displaying an OR of 0.42 (95% CI: 0.17, 0.95). This gene, as well as others identified as having functional epimutations, plays a critical role in immune system regulation and inflammatory response. In summary, a multi-omic approach was used to identify functional epimutations in the placenta that are associated with the development of ASD in children born preterm, highlighting future avenues for intervention.

Atypical cortical processing of bottom-up speech binding cues in children with autism spectrum disorders.

Individuals with autism spectrum disorder (ASD) commonly display speech processing abnormalities. Binding of acoustic features of speech distributed across different frequencies into coherent speech objects is fundamental in speech perception. Here, we tested the hypothesis that the cortical processing of bottom-up acoustic cues for speech binding may be anomalous in ASD. We recorded magnetoencephalography while ASD children (ages 7-17) and typically developing peers heard sentences of sine-wave speech (SWS) and modulated SWS (MSS) where binding cues were restored through increased temporal coherence of the acoustic components and the introduction of harmonicity. The ASD group showed increased long-range feedforward functional connectivity from left auditory to parietal cortex with concurrent decreased local functional connectivity within the parietal region during MSS relative to SWS. As the parietal region has been implicated in auditory object binding, our findings support our hypothesis of atypical bottom-up speech binding in ASD. Furthermore, the long-range functional connectivity correlated with behaviorally measured auditory processing abnormalities, confirming the relevance of these atypical cortical signatures to the ASD phenotype. Lastly, the group difference in the local functional connectivity was driven by the youngest participants, suggesting that impaired speech binding in ASD might be ameliorated upon entering adolescence.