Early sleep deprivation and attention-deficit/hyperactivity disorder.

BACKGROUND: This study aims to study prospectively specific sleep patterns and risk of ADHD after adjusting for potential confounders such as obstructive sleep apnoea (OSA) and methylphenidate use. METHODS: A population-representative sample of 514 Chinese preschool children was recruited when in kindergarten (K3). Parents reported on their socioeconomic status and children's sleep duration. The cohort was reassessed 3 years later when the children were in Grade 3 (P3). Parents reported on children's sleep patterns and ADHD symptoms. Information on OSA diagnosis and methylphenidate use was retrieved from health records. RESULTS: Among the 514 parent-child dyads (mean [SD] age, 5.52 [0.33] years), 411 were reassessed (80.0% retention; 9.35 [0.33] years) at follow-up. There were no significant baseline differences between follow-up and drop-out groups. A gradient relationship was observed between probable ADHD in P3 and sleep duration in K3. The risk of probable ADHD was 15.5 per 100 for children with <8 h of sleep in K3, whereas it was 1.1 per 100 for children with 11-12 h of sleep in K3. The adjusted risk ratio was 14.19 (p = 0.02). CONCLUSIONS: Sleep deprivation in early childhood is associated with higher risk of ADHD in middle childhood.

Mitigating adverse social determinants of health in the vulnerable population: Insights from a home visitation programme.

Introduction: Low-income families are exposed to adverse childhood experiences and psychosocial risks that impact child development. At the KK Women's and Children's Hospital in Singapore, Kids Integrated Development Service (KIDS0-3) is a home visitation programme that aims to optimise the development of children from low-income families. Method: Data comprising family demographics, maternal psychosocial risks and outcomes of child development were collated through a chart review of 469 mother-child dyads enrolled from June 2014 to October 2022. Results: Based on the Family and Adult Support Tool, 312 families (67%) were identified as moderate or high-risk. Children from moderate and high-risk families had poorer Bayley cognitive (mean 95.88 [SD 8.25] versus [vs] 98.44 [SD 8.72], P=0.014) and language scores (mean 87.38 [SD 10.35] vs 90.43 [SD 9.61], P=0.016] at 24 months of age, compared to the low-risk group. Children of teenage mothers had lower Bayley cognitive scores (mean 95.16 [SD 8.42] vs 97.76 [SD 8.55], P=0.037), and children of mothers who experienced sexual abuse had lower Bayley cognitive scores (mean 93.1 [SD 5.68] vs 99.7 [SD 8.17], P=0.013) and language scores (mean 82.3 [SD 12.87] vs 91.3 [SD 10.86], P=0.021]. Antenatal enrolment yielded better child language (mean 90.1 [SD 9.37] vs 87.13 [SD 10.79], P=0.04) and motor outcomes (mean 99.62 [SD 9.45] vs 94.72 [SD 9.51], P=0 .001) than postnatal enrolment. Conclusion: Psychosocial risks impact the development of children from low-income families in Singapore. Findings underscore the importance of early, integrated intervention for vulnerable families.

A longitudinal analysis of innate and adaptive immune profile during hepatic flares in chronic hepatitis B.

BACKGROUND & AIMS: The pathogenesis of hepatic flares (HF) in patients chronically infected with hepatitis B virus (HBV) is controversial. Therefore, we studied the kinetics of innate and adaptive immune activation during HF in chronic hepatitis B. METHODS: Soluble (IFN-alpha, IL-1beta, TNF-alpha, IL-6, IL-8, IL-10, CCL-2, CCL-3, CXCL-9, CXCL-10) and cellular (HBV-specific T cells, NK, Treg) immunological parameters were measured longitudinally (10 month-4 week intervals) in patients (n=5) who developed HF after therapy withdrawal and cross-sectionally in chronic (n=29) and acute hepatitis B patients (n=5). Hepatic expression of different chemokines was studied by co-incubating cytokines (IFN-alpha, IFN-gamma, TNF-alpha) and activated T, NK and monocytes with hepatocytes and hepatocyte-like cells. RESULTS: A progressive increase of HBV replication precedes HF but occurs without detection of innate immune activation, with the exception of increased serum CXCL-8. Despite the absence of increased circulatory HBV-specific T or activated NK cells, HF were temporally associated with high serum levels of IFN-gamma inducible chemokines CXCL-9 and CXCL-10 (but not CCL-2 or CCL-3). CXCL-9 and CXCL-10 displayed different in vitro requirements for activation and are differentially produced in liver injury present in acute or chronic patients. CONCLUSIONS: CXCL-9 and CXCL-10 play a major role in the development of HF. Their differential expression in acute versus chronic patients suggests the presence of different mechanisms that govern liver injury during acute and chronic hepatitis B.

Widespread distribution of poribacteria in demospongiae.

Poribacteria were found in nine sponge species belonging to six orders of Porifera from three oceans. Phylogenetic analysis revealed four distinct poribacterial clades, which contained organisms obtained from several different geographic regions, indicating that the distribution of poribacteria is cosmopolitan. Members of divergent poribacterial clades were also found in the same sponge species in three different sponge genera.

Rasch validation of the Chinese parent-child interaction scale (CPCIS).

BACKGROUND: Proper parent-child interaction is crucial for child development, but an assessment tool in Chinese is currently lacking. This study aimed to develop and validate a parent-reported parent-child interaction scale for Chinese preschool children. METHODS: The Chinese parent-child interaction scale (CPCIS) was designed by an expert panel based on the literature and clinical observations in the Chinese context. The initial CPCIS had 14 parent-child interactive activity items. Psychometric properties of the CPCIS were examined using the Rasch model and confirmatory factor analysis (CFA). Convergent validity was investigated by the associations between CPCIS and family income, maternal education level, and children's school readiness. RESULTS: The study recruited 567 Chinese parent-child pairs from diverse socioeconomic backgrounds, who completed the CPCIS. Six out of the 14 items in the initial CPCIS were dropped due to suboptimal fit values. The refined 8-item CPCIS was shown to be valid and reliable by Rasch models and CFA. The person separation reliability and Cronbach's α of the CPCIS were 0.81 and 0.82, respectively. The CPCIS scores were positively associated with family's socioeconomic status (η2 = 0.05, P < 0.001), maternal education level (η2 = 0.08, P < 0.001), and children's school readiness (η2 = 0.01, P < 0.01). CONCLUSION: CPCIS is an easily administered, valid, and reliable tool for the assessment of parent-child interactions in Chinese families.

Mutation of gene in spinal muscular atrophy respiratory distress type I.

Spinal muscular atrophy with respiratory distress type I (SMARD1, MIM #604 320) is an uncommon variant of infantile spinal muscular atrophy type I. Distinguishing features include diaphragmatic palsy, early-onset distal limb wasting, and contracture. This report describes a Chinese male with typical features of spinal muscular atrophy with respiratory distress type I. Direct sequencing of the causative gene, the immunoglobulin mu-binding protein 2 (IGHMBP2) gene, revealed the presence of a novel frameshift mutation caused by deletion of G in exon 13 and a single base pair substitution of G to A in exon 12 resulting in substitution of isoleucine for valine.

The Utility of Developmental Checklists in Parent-held Health Records in Singapore.

OBJECTIVE: The aim of this study was to investigate parents' perceptions of developmental checklists and the child development monitoring schedule in the Singapore health booklet. METHOD: Parents of children aged 2 years 6 months to 3 years 11 months with or without developmental concerns (n = 450) completed a structured interview, and their child's health booklets were reviewed. RESULTS: Most parents reported reading and using the developmental checklists. However, only about half of them attempted the checklists with minimal help from professionals. Approximately 7 in 10 parents of children with developmental concerns found the checklists useful for identifying concerns about their child. Despite positive feedback from parents about the checklists, only about 1 in 4 parents brought their child for a 2 to 3 years developmental monitoring visit at the time of the survey, and the completion rates of the checklists were less than desirable. CONCLUSIONS: Further revisions to the checklists can include simplifying the words and sentences and providing relevant pictures to aid understanding. If the checklists are to be used for screening, standardization of how the checklists are to be completed and how children at risk of developmental delays can be identified on the checklists need to be provided. Parents' awareness of the importance of evaluating their child's development at 9 months, 18 months, and particularly at 2.5 years, needs to be raised. Developmental screening for children at these critical ages can be made mandatory. An electronic version of the health booklet is likely to facilitate implementation of developmental screening in the health care system.

T2-weighted hyperintensities (unidentified bright objects) in children with neurofibromatosis 1: their impact on cognitive function.

The impact of magnetic resonance imaging (MRI)-identified T2-weighted hyperintensities (unidentified bright objects) on the cognitive function of children with neurofibromatosis 1 is controversial. We recruited 32 right-handed children with neurofibromatosis 1 (22 boys, 10 girls) aged between 5 and 16 years (mean age 10.2 years) for magnetic resonance imaging examinations and neuropsychologic evaluation. Statistical analysis was performed to evaluate the significance of the hyperintensities. Twenty-four children had unidentified bright objects, whereas eight children did not. Using the t-test, thalamic lesions were associated with lower intellectual function (P = .031). Left globus pallidus hyperintensities were associated with a lower attention score (P = .04), and right middle cerebellar peduncle hyperintensities were associated with a lower sensorimotor score (P = .05). The size of the thalamic lesions correlated with cognitive function (P < .05). Among the group with unidentified bright objects, there was a significant association between more involved sites on the dominant hemisphere and impaired verbal function (r = -.55; P = .005). Unidentified bright objects in the thalamus, globus pallidus, and middle cerebellar peduncles and the laterality of the lesions had an impact on cognitive function.

Diffusion-weighted imaging and proton magnetic resonance spectroscopy in perinatal hypoxic-ischemic encephalopathy: association with neuromotor outcome at 18 months of age.

We evaluated early diffusion-weighted imaging findings, the quantitative apparent diffusion coefficient, and magnetic resonance spectroscopy (the presence of lactate and ratios of N-acetylaspartate to total creatine and choline to total creatine) in the prediction of the 18-month neuromotor outcome of term newborns with hypoxic-ischemic encephalopathy. Conventional T1- and T2-weighted and diffusion-weighted imaging was performed in 20 asphyxiated term newborns, with additional basal ganglia magnetic resonance spectroscopy in 15 newborns between 2 and 18 days of life (mean 7.3 days). Neuromotor outcome was dichotomized into normal and abnormal for statistical analysis. Statistically significant differences in the ratios of N-acetylaspartate to total creatine, but not apparent diffusion coefficient values and ratios of choline to total creatine, were found between infants with a normal and an abnormal outcome (Mann-Whitney U-test, P = .010). There was a significant association between the presence of a lactate peak and an abnormal outcome (chi-square test, P = .017). The presence of a lactate peak for predicting an abnormal outcome had a sensitivity of 100% and a specificity of 80%, and the odds ratio was 37.4. Ischemic lesions were more conspicuous and/or extensive on diffusion-weighted imaging in all except one neonate. The presence of normal findings on both diffusion-weighted imaging and conventional magnetic resonance imaging is predictive of a normal neuromotor outcome, whereas lactate and a reduced ratio of N-acetylaspartate to total creatine in the basal ganglia, but not an apparent diffusion coefficient, are associated with an abnormal outcome at 18 months of age.

Hepatitis B-specific T helper cell responses in uninfected infants born to HBsAg+/HBeAg- mothers.

Vertically transmitted hepatitis B virus (HBV) usually causes chronic infection. While combined active-passive immunoprophylaxis in neonates of hepatitis B surface antigen-positive (HBsAg(+)) mothers at birth prevents vertical transmission, it is not yet clear whether neonates encounter the virus or its products in the absence of hepatitis B e antigen (HBeAg). This study was undertaken to investigate HBV antigen-specific T-cell responses in vaccinated neonates of HBsAg(+)/HBeAg(-) mothers. Blood was collected from 46 HBsAg(+) mothers and their neonates (subjects) as well as 24 age-matched controls. All neonates of HBsAg(+) mothers received appropriate immunoprophylaxis, and HBsAg and hepatitis B surface antibody (anti-HBs) antibody titers were determined after completion of the vaccination course. Peripheral blood mononuclear cells (PBMCs) from infants at birth, 1 and 6 months of age were stimulated with recombinant HBsAg, hepatitis B core antigen (HBcAg) and mitogen, and interferon (IFN)-γ concentrations were determined by ELISA. HBsAg-induced production of IL-2, IL-5, IL-6 and IL-10 was assessed using a cytometric bead array kit on cells from 6-month-old neonates post-vaccination. All neonates were HBsAg(-) and responded to vaccination. Increased IFN-γ production following HBcAg stimulation was seen in 30.4% of neonates born to HBsAg(+)/HBeAg(-) mothers. Subjects demonstrated significantly higher IL-2 production post-HBsAg stimulation, whereas IL-5, IL-6 and IL-10 cytokine responses were not significantly different. Almost one-third of uninfected neonates developed viral antigen-induced IFN-γ production, suggesting that they had been exposed to virions or viral derivatives. This encounter, however, did not impair their T-cell responses to vaccination.

Pediatric epilepsy and first afebrile seizure in Singapore: epidemiology and investigation yield at presentation.

The authors studied pediatric epilepsy and first afebrile seizure at presentation in Singapore. A total of 211 participants aged 1 month to 15 years with first presentation for afebrile seizures were recruited from November 2002 to May 2004; 108 with ≥2 prior afebrile seizures (newly diagnosed epilepsy) and 103 with first afebrile seizures. A χ(2) analysis of demographics, risk factors, examination, and investigation findings showed significant differences in development (normal in 87% [newly diagnosed epilepsy] and 93% [first afebrile seizure], P = .046), neurological examination (normal in 92% [newly diagnosed epilepsy] and 98% [first afebrile seizure], P = .016), and electroencephalogram findings (abnormal in 75% [newly diagnosed epilepsy] and 36.9% [first afebrile seizure], P < .005). Pediatric epilepsy incidence at our institution is 24 per 100 000 person-years and is highest in early childhood. Focal epilepsy is more common than generalized epilepsy. Patients with first afebrile seizure and abnormal development, neurological examination, and electroencephalogram findings should be monitored for future development of epilepsy. Population-based studies are recommended.

Dissection of double-stranded RNA binding protein B2 from betanodavirus.

Betanodaviruses are small RNA viruses that infect teleost fish and pose a considerable threat to marine aquaculture production. These viruses possess a small protein, termed B2, which binds to and protects double-stranded RNA. This prevents cleavage of virus-derived double-stranded RNAs (dsRNAs) by Dicer and subsequent production of small interfering RNA (siRNA), which would otherwise induce an RNA-silencing response against the virus. In this work, we have performed charged-to-alanine scanning mutagenesis of the B2 protein in order to identify residues required for dsRNA binding and protection. While the majority of the 19 mutated B2 residues were required for maximal dsRNA binding and protection in vitro, residues R53 and R60 were essential for both activities. Subsequent experiments in fish cells confirmed these findings by showing that mutations in these residues abolished accumulation of both the RNA1 and RNA2 components of the viral genome, in addition to preventing any significant induction of the host interferon gene, Mx. Moreover, an obvious positive correlation was found between dsRNA binding and protection in vitro and RNA1, RNA2, and Mx accumulation in fish cells, further validating the importance of the selected amino acid residues. The same trend was also demonstrated using an RNA silencing system in HeLa cells, with residues R53 and R60 being essential for suppression of RNA silencing. Importantly, we found that siRNA-mediated knockdown of Dicer dramatically enhanced the accumulation of a B2 mutant. In addition, we found that B2 is able to induce apoptosis in fish cells but that this was not the result of dsRNA binding.

White matter volume and anisotropy in preterm children: a pilot study of neurocognitive correlates.

The objectives of this study were to evaluate the differences in whole brain white matter (WM) volume and anisotropy between preterm and term children and to determine the relationships with cognitive outcome. Twenty-five low birth weight (BW), preterm, neurologically normal children between 8.8 and 11.5 y of age were recruited for volumetric and diffusion-tensor magnetic resonance imaging (DTI), together with 13 age-matched term control subjects. Subsequent intelligence quotient (IQ) testing was performed for 21 preterm children within 6 mo of imaging studies. We computed the mean volume and fractional anisotropy (FA) of the whole brain WM and compared the differences between the two groups. Mean WM volume and FA were significantly lower in the preterm group (p = 0.014 and p < 0.001, respectively). Multiple regression analysis found both WM volume and FA to be independent variables significantly affecting full scale IQ (FSIQ) (r2 = 0.407, p = 0.021 and r2 = 0.496, p = 0.005, respectively) after adjusting for BW, gestational age (GA), and gender. In the evaluation of the whole brain WM of preterm children, we found that both volume and FA remain reduced at late childhood with both parameters significantly affecting long-term cognitive outcome.

Sequestration and protection of double-stranded RNA by the betanodavirus b2 protein.

Betanodavirus B2 belongs to a group of functionally related proteins from the sense-strand RNA virus family Nodaviridae that suppress cellular RNA interference. The B2 proteins of insect alphanodaviruses block RNA interference by binding to double-stranded RNA (dsRNA), thus preventing Dicer-mediated cleavage and the subsequent generation of short interfering RNAs. We show here that the fish betanodavirus B2 protein also binds dsRNA. Binding is sequence independent, and maximal binding occurs with dsRNA substrates greater than 20 bp in length. The binding of B2 to long dsRNA is sufficient to completely block Dicer cleavage of dsRNA in vitro. Protein-protein interaction studies indicated that B2 interacts with itself and with other dsRNA binding proteins, the interaction occurring through binding to shared dsRNA substrates. Induction of the dsRNA-dependent interferon response was not antagonized by B2, as the interferon-responsive Mx gene of permissive fish cells was induced by wild-type viral RNA1 but not by a B2 mutant. The induction of Mx instead relied solely on viral RNA1 accumulation, which is impaired in the B2 mutant. Hyperediting of virus dsRNA and site-specific editing of 5-HT2C mRNA were both antagonized by B2. RNA editing was not, however, observed in transfected wild-type or B2 mutant RNA1, suggesting that this pathway does not contribute to the RNA1 accumulation defect of the B2 mutant. We thus conclude that betanodavirus B2 is a dsRNA binding protein that sequesters and protects both long and short dsRNAs to protect betanodavirus from cellular RNA interference.

Video-fluoroscopic study of swallowing in children with neurodevelopmental disorders.

BACKGROUND: Children with neurodevelopmental disorders can have feeding problems. Malnutrition and recurrent aspiration pneumonia can increase the risk of morbidity and mortality. Video-fluoroscopic study of swallowing (VFSS) is essential in understanding the pathological mechanisms involved during swallowing. METHODS: The aim of the present study was to assess the role of VFSS in assessment and management of four children with various neurodevelopmental disorders in a multidisciplinary feeding team. We describe the team approach, with the participation of child neurologist, radiologist with the rehabilitation team including the speech therapist, occupational therapist and dietician, in the assessment and plan of management. RESULTS: Video-fluoroscopic study of swallowing had been useful in assessing the type of swallowing problems with treatment goals targeted to the basic underlying pathophysiological mechanism. CONCLUSION: A child neurologist should be involved in the multidisciplinary oromotor rehabilitation program for neurologically impaired children with feeding problems.

MR imaging of spinal tumors in children with neurofibromatosis 1.

OBJECTIVE: The need for radiologic surveillance of spinal tumors in children with neurofibromatosis 1 is controversial and unresolved. We aimed to determine the incidence of spinal tumors in asymptomatic patients, describe the imaging findings, and evaluate the clinical usefulness of a prospective MR imaging surveillance program of the spine in children with neurofibromatosis 1. SUBJECTS AND METHODS: Of 62 children consecutively seen in a neurofibromatosis 1 clinic, 53 (85.5%) were recruited for MR imaging of the whole spine. All children satisfied the clinical criteria for diagnosis of neurofibromatosis 1. Imaging findings, clinical signs and symptoms, and subsequent clinical management were reviewed. RESULTS: The patients were 35 boys and 18 girls (age range, 11 months-18 years; mean age, 9.6 years), all of whom were asymptomatic, with no remarkable neurologic signs. Seven children (13.2%) had spinal neurofibromas: four had solitary neurofibromas (two dumbbell, one intradural, and one paraspinal tumor) and three had plexiform neurofibromas of the sacral plexus and thoracic and lumbar nerve sheaths. The incidences of scoliosis, localized cutaneous neurofibromas, and massive soft-tissue neurofibromas were 71.4%, 71.4%, and 28.6%, respectively, in the group with spinal neurofibromas (n = 7), and 30.4%, 39.1%, and 8.7%, respectively, in the group without spinal neurofibromas (n = 46). Patient clinical outcome was affected in only one patient (1.9%) in whom a solitary neurofibroma was resected. Follow-up imaging in 10 patients (mean period, 29 months) showed no evidence of tumor occurrence, progression, or recurrence. CONCLUSION: Although benign spinal neurofibromas are not uncommon in asymptomatic children with neurofibromatosis 1, the clinical usefulness of spine surveillance with MR imaging is limited in these children, making its effectiveness questionable.

Childhood acute disseminated encephalomyelitis: the role of brain and spinal cord MRI.

BACKGROUND: It is recognised that the clinical and radiological spectrum of childhood acute disseminated encephalomyelitis (ADEM) is wide. OBJECTIVE: To determine whether initial MRI features are predictive of clinical outcome and to determine the role of MRI in the management of ADEM. MATERIALS AND METHODS: The MRI scans of ten consecutive children (eight boys, two girls), clinically and radiologically diagnosed to have ADEM, were retrospectively reviewed. Follow-up MRI was available for eight patients. RESULTS: Lesions ranged from small and punctate (<1 cm) to moderate sized and confluent (4-5 cm) to diffuse and extensive. Spinal cord lesions, seen in five of seven children, were contiguous or segmental. Seven children (70%) made good clinical recovery while three children (30%) remained severely handicapped. There was no correlation between the site, extent and pattern of involvement and clinical outcome. However, the evolution of MRI findings on follow-up correlated well with the subsequent clinical course and outcome. CONCLUSIONS: Although the extent and site of lesions on initial MRI scans are not predictive of clinical outcome, early MRI of the brain and spine is useful in aiding clinical diagnosis, and subsequent follow-up MRI is helpful in monitoring disease progression.