Mekibib Altaye

Noroviruses bind to human ABO, Lewis, and secretor histo-blood group antigens: Identification of 4 distinct strain-specific patterns

We characterized the binding of 8 Noroviruses (NORs) to histo-blood group antigens (HBGAs) in human saliva using recombinant NOR (rNOR) capsid proteins. Among the 8 rNORs tested, 6 formed viruslike particles (VLPs) when the capsid proteins were expressed in insect cells, all of which revealed variable binding activities with saliva; the remaining 2 rNORs did not form VLPs, and the proteins did not bind, or bound weakly, to saliva. Four distinct binding patterns were associated with different histo-blood types, defined by Lewis, secretor, and ABO types. Three patterns (VA387, NV, and MOH) recognized secretors, and 1 pattern (VA207) recognized Lewis-positive nonsecretors. The 3 secretor-recognizing patterns were defined as A/B (MOH), A/O (NV), and A/B/O (VA387) binders. Oligosaccharides containing the Lewis and ABH antigenic epitopes were involved in binding. Our findings suggest that different strains of NORs may recognize different human HBGAs on intestinal epithelial cells as receptors for infection.

Elevated cytokine levels in children with autism spectrum disorder

UNLABELLED This study compared production of IL-2, IFN-gamma, IL-4, IL-13, IL-5 and IL-10 in peripheral blood mononuclear cells from 20 children with autism spectrum disorder to those from matched controls. Levels of all Th2 cytokines were significantly higher in cases after incubation in media alone, but the IFN-gamma/IL-13 ratio was not significantly different between cases and controls. Cases had significantly higher IL-13/IL-10 and IFN-gamma/IL-10 than controls. CONCLUSION Children with ASD had increased activation of both Th2 and Th1 arms of the adaptive immune response, with a Th2 predominance, and without the compensatory increase in the regulatory cytokine IL-10.

Template-O-Matic: a toolbox for creating customized pediatric templates.

Processing pediatric neuroimaging data is a challenge due to pervasive morphological changes that occur in the human brain during normal development. This is of special relevance when reference data is used as part of the processing approach, as in spatial normalization and tissue segmentation. Current approaches construct reference data (templates) by averaging brain images from a control group of subjects, or by creating custom templates from the group under study. In this technical note, we describe a new, and generalized method of constructing such appropriate reference data by statistically analyzing a large sample (n=404) of healthy children, as acquired during the NIH MRI study of normal brain development. After eliminating non-contributing demographic variables, we modeled the effects of age (first, second, and third-order terms) and gender, for each voxel in gray matter and white matter. By appropriate weighting with the parameter estimates from these analyses, complete tissue maps can be generated automatically from this database to match a pediatric population selected for study. The algorithm is implemented in the form of a toolbox for the SPM5 image data processing suite, which we term Template-O-Matic. We compare the performance of this approach with the current method of template generation and discuss the implications of our approach.

Pediatric Sports-Related Concussion Produces Cerebral Blood Flow Alterations

Objectives: The pathophysiology of sports-related concussion (SRC) is incompletely understood. Human adult and experimental animal investigations have revealed structural axonal injuries, decreases in the neuronal metabolite N-acetyl aspartate, and reduced cerebral blood flow (CBF) after SRC and minor traumatic brain injury. The authors of this investigation explore these possibilities after pediatric SRC. Patients And Methods: Twelve children, ages 11 to 15 years, who experienced SRC were evaluated by ImPACT neurocognitive testing, T1 and susceptibility weighted MRI, diffusion tensor imaging, proton magnetic resonance spectroscopy, and phase contrast angiography at <72 hours, 14 days, and 30 days or greater after concussion. A similar number of age- and gender-matched controls were evaluated at a single time point. Results: ImPACT results confirmed statistically significant differences in initial total symptom score and reaction time between the SRC and control groups, resolving by 14 days for total symptom score and 30 days for reaction time. No evidence of structural injury was found on qualitative review of MRI. No decreases in neuronal metabolite N-acetyl aspartate or elevation of lactic acid were detected by proton magnetic resonance spectroscopy. Statistically significant alterations in CBF were documented in the SRC group, with reduction in CBF predominating (38 vs 48 mL/100 g per minute; P = .027). Improvement toward control values occurred in only 27% of the participants at 14 days and 64% at >30 days after SRC. Conclusions: Pediatric SRC is primarily a physiologic injury, affecting CBF significantly without evidence of measurable structural, metabolic neuronal or axonal injury. Further study of CBF mechanisms is needed to explain patterns of recovery.

A longitudinal functional magnetic resonance imaging study of language development in children 5 to 11 years old

Language skills continue to develop rapidly in children during the school‐age years, and the “snapshot” view of the neural substrates of language provided by current neuroimaging studies cannot capture the dynamic changes associated with brain development. The aim of this study was to conduct a 5‐year longitudinal investigation of language development using functional magnetic resonance imaging in healthy children.

Influenza Immunization in Pregnancy — Antibody Responses in Mothers and Infants

The authors present antibody data for mothers and infants from a trial of influenza vaccine in pregnant women. The observations suggest that maternal immunization results in the presence of antibody titers against influenza A vaccine subtypes in a high proportion of mothers and their newborns.

Infant Brain Probability Templates for MRI Segmentation and Normalization

Spatial normalization and segmentation of infant brain MRI data based on adult or pediatric reference data may not be appropriate due to the developmental differences between the infant input data and the reference data. In this study we have constructed infant templates and a priori brain tissue probability maps based on the MR brain image data from 76 infants ranging in age from 9 to 15 months. We employed two processing strategies to construct the infant template and a priori data: one processed with and one without using a priori data in the segmentation step. Using the templates we constructed, comparisons between the adult templates and the new infant templates are presented. Tissue distribution differences are apparent between the infant and adult template, particularly in the gray matter (GM) maps. The infant a priori information classifies brain tissue as GM with higher probability than adult data, at the cost of white matter (WM), which presents with lower probability when compared to adult data. The differences are more pronounced in the frontal regions and in the cingulate gyrus. Similar differences are also observed when the infant data is compared to a pediatric (age 5 to 18) template. The two-pass segmentation approach taken here for infant T1W brain images has provided high quality tissue probability maps for GM, WM, and CSF, in infant brain images. These templates may be used as prior probability distributions for segmentation and normalization; a key to improving the accuracy of these procedures in special populations.

Evidence for Higher Reaction Time Variability for Children With ADHD on a Range of Cognitive Tasks Including Reward and Event Rate Manipulations

OBJECTIVE The purpose of the research study was to examine the manifestation of variability in reaction times (RT) in children with attention deficit hyperactivity disorder (ADHD) and to examine whether RT variability presented differently across a variety of neuropsychological tasks, was present across the two most common ADHD subtypes, and whether it was affected by reward and event rate (ER) manipulations. METHOD Children with ADHD-combined type (n = 51), ADHD-predominantly inattentive type (n = 53), and 47 controls completed five neuropsychological tasks (Choice Discrimination Task, Child Attentional Network Task, Go/No-Go task, Stop Signal Task, and N-back task), each allowing trial-by-trial assessment of RTs. Multiple indicators of RT variability including RT standard deviation, coefficient of variation and ex-Gaussian tau were used. RESULTS Children with ADHD demonstrated greater RT variability than controls across all five tasks as measured by the ex-Gaussian indicator tau. There were minimal differences in RT variability across the ADHD subtypes. Children with ADHD also had poorer task accuracy than controls across all tasks except the Choice Discrimination task. Although ER and reward manipulations did affect childrens RT variability and task accuracy, these manipulations largely did not differentially affect children with ADHD compared to controls. RT variability and task accuracy were highly correlated across tasks. Removing variance attributable to RT variability from task accuracy did not appreciably affect between-groups differences in task accuracy. CONCLUSIONS High RT variability is a ubiquitous and robust phenomenon in children with ADHD.

Prenatal Exposure to Bisphenol A and Phthalates and Infant Neurobehavior

OBJECTIVE To examine the association of prenatal exposure to bisphenol A and select common phthalates with infant neurobehavior measured at 5 weeks. METHODS We compared the concentration of maternal urinary metabolites of bisphenol A and phthalates at two distinct time points in pregnancy (16w, 26w) with scores on the NICU Network Neurobehavioral Scale (NNNS) at 5 weeks of age in a cohort of 350 mother/infant pairs. RESULTS Prenatal exposure to BPA was not significantly associated with neurobehavioral outcomes at 5 weeks. Significant associations between prenatal exposure to measured phthalates and infant neurobehavioral outcomes differed by type of phthalate and were only seen with exposure measured at 26 weeks. Higher total di-butyl phthalate (DBP) metabolites at 26w were associated with improved behavioral organization evidenced by decreased arousal (p=.04), increased self-regulation (p=.052), and decreased handling (p=.02). In males, higher total di-2-ethylhexyl phthalate (DEHP) metabolites at 26w were associated with more nonoptimal reflexes (p=.02). CONCLUSION The association between prenatal phthalate exposure and infant neurobehavior differed by type of phthalate and was evident only with exposure measured at 26w. Prenatal exposure to DBP was associated with improved behavioral organization in 5-week-old infants. Prenatal exposure to DEHP was associated with nonoptimal reflexes in male infants. There was no evidence of an association between prenatal BPA exposure and infant neurobehavior.

Middle cerebral artery peak systolic velocity: Technique and variability

Assessment of the middle cerebral artery (MCA) peak systolic velocity (PSV) can accurately diagnose fetal anemia and has decreased the number of invasive procedures, such as amniocentesis and cordocentesis. The objective of this investigation was to evaluate the intraobserver and interobserver variability as a measure of reproducibility of MCA PSV. The technique of correctly sampling this vessel is described.