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BMJ Paediatrics Open May 2024The impact of schools closing for in-person instruction in the USA during the COVID-19 pandemic on the use of prescription medications is not known. In this study, we...
The impact of schools closing for in-person instruction in the USA during the COVID-19 pandemic on the use of prescription medications is not known. In this study, we examined changes in the total prescriptions filled, specifically for attention deficit hyperactivity disorder (ADHD) medications, among school-aged children and adolescents aged 10-19 years during periods before and after complete school closures between October 2019 and September 2022. Our findings indicate that complete school closures were associated with declines in the use of ADHD medications among younger populations in the USA. These findings suggest that the underuse of ADHD medications may be an overlooked contributor to declines in academic performance observed during periods of school closures during the COVID-19 pandemic.
Topics: Humans; Adolescent; COVID-19; Child; United States; Schools; Male; Female; Attention Deficit Disorder with Hyperactivity; SARS-CoV-2; Young Adult; Pandemics; Prescription Drugs; Drug Prescriptions
PubMed: 38823800
DOI: 10.1136/bmjpo-2024-002632 -
BMJ Paediatrics Open May 2024To compare the neurodevelopmental outcomes of preterm infants before and during the COVID-19 pandemic.
OBJECTIVE
To compare the neurodevelopmental outcomes of preterm infants before and during the COVID-19 pandemic.
DESIGN
Premature infants born in 2018 were assigned to the pre-pandemic group, while those born in 2019 were assigned to the during-pandemic group.
SETTING
Nationwide cohort study.
PATIENTS
Very low birthweight premature infants registered in the Taiwan Premature Infant Follow-up Network database.
INTERVENTIONS
Anti-epidemic measures, including quarantine and isolation protocols, social distancing, the closure of public spaces and restrictions on travel and gatherings during COVID-19 pandemic.
MAIN OUTCOME MEASURES
Outcomes were measured by Bayley Scales of Infant and Toddler Development Third Edition at corrected ages of 6, 12 and 24 months old. Generalised estimating equation (GEE) was applied to incorporate all measurements into a single model.
RESULTS
Among the 1939 premature infants who were enrolled, 985 developed before the pandemic, while 954 developed during the pandemic. Premature infants whose development occurred during the pandemic exhibited better cognitive composite at the corrected age of 6 months (beta=2.358; 95% CI, 1.07 to 3.65; p<0.001), and motor composite at corrected ages of 12 months (beta=1.680; 95% CI, 0.34 to 3.02; p=0.014). GEE analysis showed that infants who had grown during the pandemic achieved higher scores in cognitive composite (beta=1.416; 95% CI, 0.36 to 2.48; p=0.009).
CONCLUSION
Premature infants in Taiwan who developed during the pandemic showed better neurodevelopment compared with those born before the pandemic.
Topics: Humans; COVID-19; Taiwan; Infant, Premature; Male; Female; Infant, Newborn; Infant; Retrospective Studies; Child Development; SARS-CoV-2; Neurodevelopmental Disorders; Infant, Very Low Birth Weight; Pandemics; Cohort Studies
PubMed: 38823798
DOI: 10.1136/bmjpo-2024-002493 -
Neurology India Mar 2024There are a few comprehensive genetic studies on autism spectrum disorders (ASD) in India. Children of multiple births are valuable for genomics studies of complex...
There are a few comprehensive genetic studies on autism spectrum disorders (ASD) in India. Children of multiple births are valuable for genomics studies of complex disorders such as ASD. We report whole-exome sequencing (WES) in a triplet family in which only one among the triplet has ASD. The objective of this study was to identify potential candidate genes for ASD. Exome DNA was enriched using a twist human customized core exome kit, and paired-end sequencing was performed. Proband-specific de novo variants included 150 single nucleotide polymorphisms (SNPs) and 74 indels. Thirteen SNPs were in exonic regions, 7 of them being missense variations. Seventeen variants were previously reported in ASD. Genes harboring variants have functions in the development and maintenance of the central nervous system and are enriched in biological processes involving cell adhesion. This is the first comprehensive genetic study of a monozygotic triplet in ASD.
Topics: Humans; Autism Spectrum Disorder; Male; Polymorphism, Single Nucleotide; Triplets; Exome Sequencing; Female; Child
PubMed: 38817175
DOI: 10.4103/ni.ni_349_22 -
Turkish Journal of Medical Sciences 2023Hypoxic ischemic encephalopathy (HIE) is one of the common causes of mortality and morbidity in newborns. Despite therapeutic hypothermia, an important treatment with...
BACKGROUND/AIM
Hypoxic ischemic encephalopathy (HIE) is one of the common causes of mortality and morbidity in newborns. Despite therapeutic hypothermia, an important treatment with proven efficacy, the morbidity and mortality rates remain high. The aim of this study was to neurodevelopmentally evaluate patients who underwent therapeutic hypothermia.
MATERIAL AND METHOD
Included herein were patients who underwent hypothermia between 2018 and 2020. Their medical files were reviewed retrospectively, and their demographic and clinical information was recorded. Patients whose contact information was available were called to the developmental pediatrics outpatient clinic for a neurodevelopmental evaluation. The Bayley Scales of Infant and Toddler Development 3rd Edition (Bayley-III) was used as the evaluation tool. Laboratory values and clinical parameters of the patients were further analyzed.
RESULTS
It was found that 42 patients underwent hypothermia in 3 years, of whom 14 (33.3%) had died. Of the 28 patients who were discharged, 20 children could be reached, and a neurodevelopmental evaluation was performed. Developmental delay in the cognitive area was detected in 11 (55%) patients, delay in the language area was found in 9 (45%) patients, and delay in the motor area was found in 11 (55%) patients. The correlation and regression analysis results determined that the time to start cooling was the most effective common factor in all 3 fields of scoring.
CONCLUSION
The time to start cooling is related to the neurodevelopmental outcomes of patients with HIE. The earlier cooling is started, the better the neurodevelopmental results. Despite therapeutic hypothermia, the neurodevelopmental development of infants may be adversely affected. These patients should be followed-up neurodevelopmentally for a long time.
Topics: Humans; Hypoxia-Ischemia, Brain; Hypothermia, Induced; Male; Female; Infant, Newborn; Retrospective Studies; Neurodevelopmental Disorders; Infant; Child, Preschool; Developmental Disabilities
PubMed: 38813516
DOI: 10.55730/1300-0144.5748 -
Turkish Journal of Medical Sciences 2023Williams-Beuren syndrome (WBS) is a rare genetic disorder with delays in language and cognitive development, but, with increased awareness of clinical features and a...
BACKGROUND/AIM
Williams-Beuren syndrome (WBS) is a rare genetic disorder with delays in language and cognitive development, but, with increased awareness of clinical features and a reliable diagnostic test, WBS is becoming more widely recognized in childhood. Adaptive behavior skills and/or maladaptive behavior are important for the prognosis of individuals with WBS. The aim of this study was to investigate the clinical and developmental characteristics of patients with WBS and further increase awareness about it by evaluating the adaptive skills and maladaptive behaviors of the patients.
MATERIALS AND METHODS
The data of WBS patients followed-up at the Developmental Behavioral Pediatrics Unit were reviewed. Patient data on perinatal and postnatal history, developmental stages, physical and neurological examination findings were collected. The International Guide for Monitoring Child Development (GMCD) was administered to each child. In addition, semistructured interviews were conducted with the parents using the Vineland Adaptive Behavior Scales, Second edition (Vineland-II).
RESULTS
A total of 12 patients diagnosed with WBS via detection of the 7q11.23 deletion, of whom 6 were girls, were retrospectively reviewed. The mean age at the time of review was 54.6 ± 32.5 months. The mean age at first presentation to the Developmental Behavioral Pediatrics Outpatient Clinic was 15 ± 11.5 months. In the first developmental evaluation using the GMCD, there was a delay in fine and gross motor domains in 6 patients, in the language domains in 4 patients, and in all of the domains in 2 patients. Findings with Vineland-II showed socialization and communication domains as strengths, but the daily living skills and motor skills domains were weaknesses. In terms of maladaptive behavior, the patients tended to frequently have behavioral problems, neurodevelopmental disease, anxiety disorders, eating problems, and sleeping problems.
CONCLUSION
This retrospective review of 12 patients indicated a general delay in overall development, and confirmed impairment in both adaptive and maladaptive functioning in WBS.
Topics: Humans; Williams Syndrome; Female; Child, Preschool; Male; Infant; Retrospective Studies; Adaptation, Psychological; Child; Child Development
PubMed: 38812996
DOI: 10.55730/1300-0144.5701 -
Frontiers in Cellular Neuroscience 2024Neural stem cells (NSCs) are essential for both embryonic development and adult neurogenesis, and their dysregulation causes a number of neurodevelopmental disorders,...
INTRODUCTION
Neural stem cells (NSCs) are essential for both embryonic development and adult neurogenesis, and their dysregulation causes a number of neurodevelopmental disorders, such as epilepsy and autism spectrum disorders. NSC proliferation and differentiation in the developing brain is a complex process controlled by various intrinsic and extrinsic stimuli. The mammalian target of rapamycin (mTOR) regulates proliferation and differentiation, among other cellular functions, and disruption in the mTOR pathway can lead to severe nervous system development deficits. In this study, we investigated the effect of inhibition of the mTOR pathway by rapamycin (Rapa) on NSC proliferation and differentiation.
METHODS
The NSC cultures were treated with Rapa for 1, 2, 6, 24, and 48 h. The effect on cellular functions was assessed by immunofluorescence staining, western blotting, and proliferation/metabolic assays.
RESULTS
mTOR inhibition suppressed NSC proliferation/metabolic activity as well as S-Phase entry by as early as 1 h of Rapa treatment and this effect persisted up to 48 h of Rapa treatment. In a separate experiment, NSCs were differentiated for 2 weeks after treatment with Rapa for 24 or 48 h. Regarding the effect on neuronal and glial differentiation (2 weeks post-treatment), this was suppressed in NSCs deficient in mTOR signaling, as evidenced by downregulated expression of NeuN, MAP2, and GFAP. We assume that the prolonged effect of mTOR inhibition is realized due to the effect on cytoskeletal proteins.
DISCUSSION
Here, we demonstrate for the first time that the mTOR pathway not only regulates NSC proliferation but also plays an important role in NSC differentiation into both neuronal and glial lineages.
PubMed: 38812794
DOI: 10.3389/fncel.2024.1298182 -
Journal of Integrative Neuroscience May 2024Hypoxic-ischemic encephalopathy (HIE) is a prominent cause of neonatal mortality and neurodevelopmental disorders; however, effective therapeutic interventions remain... (Review)
Review
Hypoxic-ischemic encephalopathy (HIE) is a prominent cause of neonatal mortality and neurodevelopmental disorders; however, effective therapeutic interventions remain limited. During neonatal hypoxic-ischemic injury events, increased reactive oxygen species (ROS) production and decreased antioxidant levels lead to the induction of oxidative stress, which plays a pivotal role in the pathological process of neonatal HIE. Nuclear factor erythroid 2-related factor 2 (Nrf2) is a key endogenous antioxidant transcription factor that protects against oxidative stress by promoting the transcription of various antioxidant genes. It has been demonstrated that Nrf2 signaling pathway activation by different compounds may protect against neonatal HIE. This review outlines the role of oxidative stress in neonatal HIE and summarizes the impact of antioxidants on neonatal HIE via activation of the Nrf2 signaling pathway. In conclusion, Nrf2 signaling pathway potentially exerts antioxidant, anti-inflammatory, antiapoptotic and antiferroptotic effects, thereby emerging as a focal point for future neonatal HIE treatment strategies.
Topics: Hypoxia-Ischemia, Brain; Humans; NF-E2-Related Factor 2; Infant, Newborn; Animals; Oxidative Stress; Antioxidants; Signal Transduction
PubMed: 38812389
DOI: 10.31083/j.jin2305103 -
Journal of Integrative Neuroscience May 2024Autism Spectrum Disorder (ASD) is a complex neurodevelopment disease characterized by impaired social and cognitive abilities. Despite its prevalence, reliable...
BACKGROUND
Autism Spectrum Disorder (ASD) is a complex neurodevelopment disease characterized by impaired social and cognitive abilities. Despite its prevalence, reliable biomarkers for identifying individuals with ASD are lacking. Recent studies have suggested that alterations in the functional connectivity of the brain in ASD patients could serve as potential indicators. However, previous research focused on static functional-connectivity analysis, neglecting temporal dynamics and spatial interactions. To address this gap, our study integrated dynamic functional connectivity, local graph-theory indicators, and a feature-selection and ranking approach to identify biomarkers for ASD diagnosis.
METHODS
The demographic information, as well as resting and sleeping electroencephalography (EEG) data, were collected from 20 ASD patients and 25 controls. EEG data were pre-processed and segmented into five sub-bands (Delta, Theta, Alpha-1, Alpha-2, and Beta). Functional-connection matrices were created by calculating coherence, and static-node-strength indicators were determined for each channel. A sliding-window approach, with varying widths and moving steps, was used to scan the EEG series; dynamic local graph-theory indicators were computed, including mean, standard deviation, median, inter-quartile range, kurtosis, and skewness of the node strength. This resulted in 95 features (5 sub-bands × 19 channels) for each indicator. A support-vector-machine recurrence-feature-elimination method was used to identify the most discriminative feature subset.
RESULTS
The dynamic graph-theory indicators with a 3-s window width and 50% moving step achieved the highest classification performance, with an average accuracy of 95.2%. Notably, mean, median, and inter-quartile-range indicators in this condition reached 100% accuracy, with the least number of selected features. The distribution of selected features showed a preference for the frontal region and the Beta sub-band.
CONCLUSIONS
A window width of 3 s and a 50% moving step emerged as optimal parameters for dynamic graph-theory analysis. Anomalies in dynamic local graph-theory indicators in the frontal lobe and Beta sub-band may serve as valuable biomarkers for diagnosing autism spectrum disorders.
Topics: Humans; Autism Spectrum Disorder; Electroencephalography; Male; Female; Child; Brain; Adolescent; Young Adult; Adult; Brain Waves; Signal Processing, Computer-Assisted
PubMed: 38812386
DOI: 10.31083/j.jin2305095 -
Molecular Neurodegeneration May 2024A ~ 1 Mb inversion polymorphism exists within the 17q21.31 locus of the human genome as direct (H1) and inverted (H2) haplotype clades. This inversion region... (Review)
Review
A ~ 1 Mb inversion polymorphism exists within the 17q21.31 locus of the human genome as direct (H1) and inverted (H2) haplotype clades. This inversion region demonstrates high linkage disequilibrium, but the frequency of each haplotype differs across ancestries. While the H1 haplotype exists in all populations and shows a normal pattern of genetic variability and recombination, the H2 haplotype is enriched in European ancestry populations, is less frequent in African ancestry populations, and nearly absent in East Asian ancestry populations. H1 is a known risk factor for several neurodegenerative diseases, and has been associated with many other traits, suggesting its importance in cellular phenotypes of the brain and entire body. Conversely, H2 is protective for these diseases, but is associated with predisposition to recurrent microdeletion syndromes and neurodevelopmental disorders such as autism. Many single nucleotide variants and copy number variants define H1/H2 haplotypes and sub-haplotypes, but identifying the causal variant(s) for specific diseases and phenotypes is complex due to the extended linkage equilibrium. In this review, we assess the current knowledge of this inversion region regarding genomic structure, gene expression, cellular phenotypes, and disease association. We discuss recent discoveries and challenges, evaluate gaps in knowledge, and highlight the importance of understanding the effect of the 17q21.31 haplotypes to promote advances in precision medicine and drug discovery for several diseases.
Topics: Humans; Haplotypes; Neurodegenerative Diseases; tau Proteins; Genetic Predisposition to Disease; Linkage Disequilibrium; Polymorphism, Single Nucleotide
PubMed: 38812061
DOI: 10.1186/s13024-024-00731-x -
Variant-specific pathophysiological mechanisms of AFF3 differently influence transcriptome profiles.Genome Medicine May 2024We previously described the KINSSHIP syndrome, an autosomal dominant disorder associated with intellectual disability (ID), mesomelic dysplasia and horseshoe kidney,...
BACKGROUND
We previously described the KINSSHIP syndrome, an autosomal dominant disorder associated with intellectual disability (ID), mesomelic dysplasia and horseshoe kidney, caused by de novo variants in the degron of AFF3. Mouse knock-ins and overexpression in zebrafish provided evidence for a dominant-negative mode of action, wherein an increased level of AFF3 resulted in pathological effects.
METHODS
Evolutionary constraints suggest that other modes-of-inheritance could be at play. We challenged this hypothesis by screening ID cohorts for individuals with predicted-to-be damaging variants in AFF3. We used both animal and cellular models to assess the deleteriousness of the identified variants.
RESULTS
We identified an individual with a KINSSHIP-like phenotype carrying a de novo partial duplication of AFF3 further strengthening the hypothesis that an increased level of AFF3 is pathological. We also detected seventeen individuals displaying a milder syndrome with either heterozygous Loss-of-Function (LoF) or biallelic missense variants in AFF3. Consistent with semi-dominance, we discovered three patients with homozygous LoF and one compound heterozygote for a LoF and a missense variant, who presented more severe phenotypes than their heterozygous parents. Matching zebrafish knockdowns exhibit neurological defects that could be rescued by expressing human AFF3 mRNA, confirming their association with the ablation of aff3. Conversely, some of the human AFF3 mRNAs carrying missense variants identified in affected individuals did not rescue these phenotypes. Overexpression of mutated AFF3 mRNAs in zebrafish embryos produced a significant increase of abnormal larvae compared to wild-type overexpression further demonstrating deleteriousness. To further assess the effect of AFF3 variation, we profiled the transcriptome of fibroblasts from affected individuals and engineered isogenic cells harboring + / + , KINSSHIP/KINSSHIP, LoF/ + , LoF/LoF or KINSSHIP/LoF AFF3 genotypes. The expression of more than a third of the AFF3 bound loci is modified in either the KINSSHIP/KINSSHIP or the LoF/LoF lines. While the same pathways are affected, only about one third of the differentially expressed genes are common to the homozygote datasets, indicating that AFF3 LoF and KINSSHIP variants largely modulate transcriptomes differently, e.g. the DNA repair pathway displayed opposite modulation.
CONCLUSIONS
Our results and the high pleiotropy shown by variation at this locus suggest that minute changes in AFF3 function are deleterious.
Topics: Humans; Animals; Zebrafish; Transcriptome; Intellectual Disability; Phenotype; Female; Male; Mutation, Missense; Loss of Function Mutation
PubMed: 38811945
DOI: 10.1186/s13073-024-01339-y