Reduced inhibition control ability in children with ADHD due to coexisting learning disorders: an fNIRS study.

Introduction: Inhibition control, as the core component of executive function, might play a crucial role in the understanding of attention deficit/hyperactivity disorder (ADHD) and specific learning disorders (SLD). Inhibition control deficits have been observed in children with ADHD or SLD. This study sought to test in a multi-modal fashion (i.e., behavior and plus brain imaging) whether inhibition control abilities would be further deteriorated in the ADHD children due to the comorbidity of SLD. Method: A total number of 90 children (aged 6-12 years) were recruited, including 30 ADHD, 30 ADHD+SLD (children with the comorbidity of ADHD and SLD), and 30 typically developing (TD) children. For each participant, a 44-channel functional near infrared spectroscopy (fNIRS) equipment was first adopted to capture behavioral and cortical hemodynamic responses during a two-choice Oddball task (a relatively new inhibition control paradigm). Then, 50 metrics were extracted, including 6 behavioral metrics (i.e., OddballACC, baselineACC, totalACC, OddballRT, baselineRT, and totalRT) and 44 beta values in 44 channels based on general linear model. Finally, differences in those 50 metrics among the TD, ADHD, and ADHD+SLD children were analyzed. Results: Findings showed that: (1) OddballACC (i.e., the response accuracy in deviant stimuli) is the most sensitive metric in identifying the differences between the ADHD and ADHD+SLD children; and (2) The ADHD+SLD children exhibited decreased behavioral response accuracy and brain activation level in some channels (e.g., channel CH35) than both the ADHD and TD children. Discussion: Findings seem to support that inhibition control abilities would be further decreased in the ADHD children due to the comorbidity of SLD.

The dairy-derived peptide Miltin exerts anti-obesity effects by increasing adipocyte thermogenesis.

Growing research has highlighted that the consumption of dairy products improves the metabolic health in obese individuals by functioning as regulatory modulators. However, the molecular basis of this effect remains largely unknown. Herein, we report a dairy-derived peptide, which we named Miltin, that activates the thermogenesis of brown adipocytes and increases white adipocyte browning. Previously, Miltin was merely identified for its antioxidant capacity, although it is commonly present in different dairy products. In this study, we revealed the effect of Miltin in modulating adipose thermogenesis and further explored its potential in treating obesity through in vivo and in vitro strategies. The administration of Miltin in mice fed with a high-fat diet resulted in enhanced thermogenesis, improved glucose homeostasis, and reduced body mass and lipid accumulation, indicating the anti-obesity effect of Miltin. Genomic analysis revealed that Miltin modulates thermogenesis by inducing the activation of the MAPK signaling pathway by preferentially interacting with GADD45γ to promote its stability. Together, our findings indicate that Miltin's role in initiating the thermogenesis of adipocytes makes it a potential anti-obesity therapy for future development.

Newborn genetic screening for Fabry disease: Insights from a retrospective analysis in Nanjing, China.

Fabry disease (FD), an X-linked disorder resulting from dysfunction of α-galactosidase A, can result in significant complications. Early intervention yields better outcomes, but misdiagnosis or delayed diagnosis is common, impacting prognosis. Thus, early detection is crucial in the clinical diagnosis and treatment of FD. While newborn screening for FD has been implemented in certain regions, challenges persist in enzyme activity detection techniques, particularly for female and late-onset patients. Further exploration of improved screening strategies is warranted. This study retrospectively analyzed genetic screening results for pathogenic GLA variants in 17,171 newborns. The results indicated an estimated incidence of FD in the Nanjing region of China of approximately 1 in 1321. The most prevalent pathogenic variant among potential FD patients was c.640-801G > A (46.15 %). Furthermore, the residual enzyme activity of the pathogenic variant c.911G > C was marginally higher than that of other variants, and suggesting that genetic screening may be more effective in identifying potential female and late-onset patients compared to enzyme activity testing. This research offers initial insights into the effectiveness of GLA genetic screening and serves as a reference for early diagnosis, treatment, and genetic counseling in FD.

[Association between auditory processing and problem behaviors in preschool children: the mediating role of executive function]. / å¬å¤„ç†ä¸Žå­¦é¾„å‰å„¿ç«¥é—®é¢˜è¡Œä¸ºçš„å ³ç³»ï¼šæ‰§è¡ŒåŠŸèƒ½çš„ä¸­ä»‹ä½œç”¨.

OBJECTIVES: To investigate the association between auditory processing and problem behaviors in preschool children, as well as the mediating role of executive function. METHODS: A total of 2 342 preschool children were selected from 7 kindergartens in Nanjing, China from June to August 2021. They were evaluated using Preschool Auditory Processing Assessment Scale, Conners Parent Symptom Questionnaire, and Behavior Rating Inventory of Executive Functioning-Preschool version. Children with different demographic features were compared in the scores and the abnormality rates of auditory processing, problem behaviors, and executive function. The influencing factors of the total scores of auditory processing, problem behaviors, and executive function were evaluated using multiple linear regression analysis. Whether executive function was a mediating factor between auditory processing and executive function was examined. RESULTS: Sex and grade were the main influencing factors for the total score of auditory processing (P<0.05), and sex, grade, parental education level, and family economic status were the main influencing factors for the total scores of problem behaviors and executive function (P<0.05). The auditory processing score (rs=0.458, P<0.05) and problem behavior score (rs=0.185, P<0.05) were significantly positively correlated with the executive function score, and the auditory processing score was significantly positively correlated with the problem behavior score (rs=0.423, P<0.05). Executive function played a partial mediating role between auditory processing and problem behaviors, and the mediating effect accounted for 33.44% of the total effect. CONCLUSIONS: Auditory processing can directly affect the problem behaviors of preschool children and indirectly affect problem behaviors through executive function.

Vitamin A ameliorates valproic acid-induced autism-like symptoms in developing zebrafish larvae by attenuating oxidative stress and apoptosis.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by social deficits and repetitive/stereotyped behaviors. Prenatal exposure to valproic acid (VPA) has been reported to induce ASD-like symptoms in human and rodents. However, the etiology and pathogenesis of ASD have not been well elucidated. This study aimed to explore the mechanisms underlying VPA-induced ASD-like behaviors using zebrafish model and investigated whether vitamin A could prevent VPA-induced neurotoxicity. Here, zebrafish embryos were exposed to 0, 25 and 50 µM VPA from 4 to 96 h post fertilization (hpf) and the neurotoxicity was assessed. Our results showed that VPA affected the normal development of zebrafish larvae and induced ASD-like behaviors, including reduced locomotor activity, decreased distance near conspecifics, impaired social interaction and repetitive swimming behaviors. Exposure to VPA decreased the GFP signal in transgenic HuC:egfp zebrafish according to the negative effect of VPA on the expression of neurodevelopmental genes. In addition, VPA enhanced oxidative stress by promoting the production of reactive oxygen species (ROS) and hydrogen peroxide (H2O2) and inhibiting the activity of superoxide dismutase, then triggered apoptosis by upregulation of apoptotic genes. These adverse outcomes were mitigated by vitamin A, suggesting that vitamin A rescued VPA-induced ASD-like symptoms by inhibiting oxidative stress and apoptosis. Overall, this study identified vitamin A as a promising strategy for future therapeutic regulator of VPA-induced ASD-like behaviors.

Association of Breastfeeding and Neonatal Jaundice With Infant Neurodevelopment.

INTRODUCTION: Exclusive breastfeeding is advantageous for infant neurodevelopment. Nevertheless, insufficient human milk supply in exclusively breastfed infants may elevate the risk of neonatal jaundice, which can potentially result in neurological harm. Whether mothers should adhere to exclusive breastfeeding in infants with neonatal jaundice remains unclear. METHODS: Data comes from the Jiangsu Birth Cohort (JBC), a prospective and longitudinal birth cohort study in China. A total of 2,577 infants born from November 2017 to March 2021 were included in the analysis. Multivariate linear regression models were used to analyze the associations between breastfeeding status, neonatal jaundice, and their interaction with infant neurodevelopment. Analysis was performed in 2022. RESULTS: Compared with "exclusive breastfeeding," fine motor scores of infants were lower for "mixed feeding" (ßadj, -0.16; 95% CI, -0.29 to -0.03; p=0.016) and "no breastfeeding" (ßadj, -0.41; 95% CI, -0.79 to -0.03; p=0.034). Compared with "no neonatal jaundice," infants with "severe neonatal jaundice" had lower scores for cognition (ßadj, -0.44; 95% CI, -0.66 to -0.23; p<0.001) and fine motor (ßadj, -0.19; 95% CI, -0.35 to -0.03; p=0.024). In infants with severe neonatal jaundice, the termination of exclusive breastfeeding before 6 months was associated with worse cognition (ßadj, -0.28; 95% CI, -0.57 to 0.01), while this association was not observed in those without neonatal jaundice (ßadj, 0.09; 95% CI, -0.26 to 0.43). CONCLUSIONS: Exclusive breastfeeding for the first 6 months is beneficial to the neurodevelopment of infants, especially in those with severe neonatal jaundice.

Using machine learning to explore the characteristics of eye movement patterns and relationship with cognition ability of Chinese children aged 1-6 years.

Researchers have begun to investigate the relationship between eye movement characteristics of gaze patterns and cognitive abilities, and have attempted to use eye-tracking technology as a new method to evaluate cognitive abilities. Traditional eye movement analysis methods typically separate spatial and temporal information of eye movements, mostly analyze averaged data, and consider individual differences as noise. In addition, current eye movement studies on gaze patterns mostly involve adults, while research on infants and toddlers is limited with small sample sizes and narrow age ranges. It is still unknown whether the conclusions drawn from adult-based research can be applied to children. Consequently, eye movement research on gaze patterns in children is necessary. To address the concerns stated above, this study used the Hidden Markov machine learning method to model gaze patterns of 330 children aged 1-6 years while observing faces freely, and analyzed characteristics of eye movement gaze patterns. Additionally, we analyzed the correlation between gaze patterns of 31 toddlers aged 1-3 years and 37 preschoolers aged 4-6 years, and the different dimensions of cognitive abilities. The findings indicated that children exhibited holistic and analytic gaze patterns while observing different faces freely. More children adopted a holistic gaze pattern, and there were age-specific gaze pattern characteristics and regularities. Gaze patterns of toddlers may be correlated with their adaptive abilities and gaze patterns of preschoolers may be correlated with their visual space abilities. Specifically, toddlers aged 1-3 years showed a moderate negative correlation between the H-A scale and the adaptive dimension, while preschoolers aged 4-6 years showed a low negative correlation between the H-A scale and the visual space dimension. This study may provide new insights into the characteristics of children's eye-movement gaze patterns during face observation, and potentially offer objective evidence for future research aimed at promoting the use of eye-tracking technology in the assessment of toddlers' adaptive abilities and preschoolers' visual space abilities in the field of face perception.

Improving Accuracy of ADHD Diagnosis with the Combination of Brain Imaging and Behavioral Measures.

Neuropsychological measures may improve Attention-deficit/hyperactivity disorder (ADHD) diagnostic accuracy and enhance treatment response detection. Highquality evaluation indicators are necessary for accurate diagnosis of ADHD. Due to the high complexity of the pathogenesis of ADHD, it may not be possible to accurately diagnose ADHD only by relying on behavioral assessment or brain imaging examination. Therefore, the authors propose a comprehensive index that combines brain imaging behavioral and measures. The results showed that the classification performance of the composite index was better than that of the single behavior or brain image index.Clinical Relevance- The results of this study help to remind practicing clinicians to consider the results of multiple clinical examinations when clinically diagnosing ADHD patients.

[Relationship between home literacy environment and emotional regulation in children: the mediating effect of the parent-child relationship]. / å®¶åº­é˜ è¯»çŽ¯å¢ƒä¸Žå„¿ç«¥æƒ ç»ªè°ƒèŠ‚èƒ½åŠ›çš„å ³ç³»ï¼šäº²å­å ³ç³»çš„ä¸­ä»‹ä½œç”¨.

OBJECTIVES: To study the impact of the home literacy environment on children's emotional regulation skills and the mediating role of the parent-child relationship between them. METHODS: A stratified cluster sampling approach was employed to select 1 626 preschool children from five kindergartens in Nanjing. Questionnaires were used to collect detailed information on the home literacy environment, children's emotional regulation skills, and the parent-child relationship. A mediation model was established using the Process program in SPSS macro, and the significance of the mediation effect was tested using the Bootstrap method. RESULTS: The findings revealed a positive correlation between the home literacy environment and children's emotional regulation skills (r=0.217, P<0.001), as well as parent-child intimacy (r=0.065, P<0.01). Conversely, a negative correlation was found between the home literacy environment and parent-child conflict (r=-0.129, P<0.001). Additionally, parent-child conflict demonstrated a negative correlation with children's emotional regulation skills (r=-0.443, P<0.001), while parent-child intimacy exhibited a positive correlation (r=0.247, P<0.001). The home literacy environment exerted a significant direct effect on children's emotional regulation skills (ß=0.162, P<0.001), and the mediating effect of the parent-child relationship accounted for 25.54% of the total effect. CONCLUSIONS: The home literacy environment significantly influences children's emotional regulation skills, with the parent-child relationship partially mediating this relationship.

[Application of Preschool Auditory Processing Assessment Scale in children with attention deficit hyperactivity disorder]. / å­¦é¾„å‰å„¿ç«¥å¬å¤„ç†è¯„ä¼°é‡è¡¨åœ¨æ³¨æ„ç¼ºé™·å¤šåŠ¨éšœç¢å„¿ç«¥ä¸­çš„åº”ç”¨ç ”ç©¶.

OBJECTIVES: To investigate the characteristics of auditory processing (AP) in preschool children with attention deficit hyperactivity disorder (ADHD) using Preschool Auditory Processing Assessment Scale (hereafter referred to as "auditory processing scale"). METHODS: A total of 41 children with ADHD and 41 typically developing (TD) children were assessed using the auditory processing scale, SNAP-IV rating scale, and Conners' Kiddie Continuous Performance Test (K-CPT). The auditory processing scale score was compared between the TD and ADHD groups. The correlations of the score with SNAP-IV and K-CPT scores were assessed. RESULTS: Compared with the TD group, the ADHD group had significantly higher total score of the auditory processing scale and scores of all dimensions except visual attention (P<0.05). In the children with ADHD, the attention deficit dimension score of the SNAP-IV rating scale was positively correlated with the total score of the auditory processing scale (rs30=0.531, P<0.05; rs27=0.627, P<0.05) as well as the scores of its subdimensions, including auditory decoding (rs=0.628, P<0.05), auditory attention (rs=0.492, P<0.05), and communication (rs=0.399, P<0.05). The hyperactivity-impulsivity dimension score of the SNAP-IV rating scale was positively correlated with the hyperactivity-impulsivity dimension score of the auditory processing scale (rs=0.429, P<0.05). In the children with ADHD, the attention deficit dimension score of the K-CPT was positively correlated with the total score (rs30=0.574, P<0.05; rs27=0.485, P<0.05) and the hyperactivity-impulsivity dimension score (rs=0.602, P<0.05) of the auditory processing scale. CONCLUSIONS: Preschool children with ADHD have the risk of AP abnormalities, and the auditory processing scale should be used early for the screening and evaluation of AP abnormalities in children.

NRXN1 depletion in the medial prefrontal cortex induces anxiety-like behaviors and abnormal social phenotypes along with impaired neurite outgrowth in rat.

BACKGROUND: Neurodevelopmental disorders (NDDs) are a group of disorders induced by abnormal brain developmental processes. The prefrontal cortex (PFC) plays an essential role in executive function, and its role in NDDs has been reported. NDDs are associated with high-risk gene mutations and share partially overlapping genetic abnormalities. METHODS: Neurexins (NRXNs) are related to autism spectrum disorder (ASD) and attention-deficit hyperactivity disorder (ADHD). NRXN1, an essential susceptibility gene for NDDs, has been reported to be associated with NDDs. However, little is known about its key role in NDDs. RESULTS: NRXN1 downregulation in the medial PFC induced anxiety-like behaviors and abnormal social phenotypes with impaired neurite outgrowth in Sh-NRXN1 in prefrontal neurons. Moreover, tandem mass tag (TMT)-based proteomic analysis of rat brain samples showed that NRXN1 downregulation led to significant proteome alterations, including pathways related to the extracellular matrix, cell membrane, and morphologic change. Furthermore, full-automatic immunoblotting analysis verified the differently expressed proteins related to cell morphology and membrane structure. CONCLUSIONS: Our results confirmed the association of NRXN1 with abnormal behaviors in NDDs and provided richer insights into specific prefrontal knockdown in adolescence, potentially expanding the NRXN1 interactome and contributing to human health.

Nano-TiO2 aggravates bioaccumulation and developmental neurotoxicity of difenoconazole in zebrafish larvae via oxidative stress and apoptosis: Protective role of vitamin C.

Titanium dioxide nanoparticles (n-TiO2) could enhance the bioavailability and toxicity of coexisting organic contaminants in the aquatic environment. This study attempted to investigate the combined effects of n-TiO2 and difenoconazole (DIF) on the neurodevelopment of zebrafish and the underlying mechanisms. In this study, zebrafish embryos were exposed to n-TiO2 (100 µg/L), DIF (0, 0.1 and 0.5 mg/L) and their mixtures from 4 to 96 h post fertilization (hpf) and neurotoxicity was evaluated. Our results indicated that n-TiO2 adsorbed DIF into the brain of zebrafish and significantly enhanced the bioaccumulation of DIF and n-TiO2 in the 0.5 mg/L co-exposure group. 100 µg/L n-TiO2 was not developmentally toxic to the zebrafish larvae, but it exacerbated DIF-induced neurobehavioral alterations in the zebrafish larvae. n-TiO2 also aggravated DIF-induced suppression of central nervous system (CNS) neurogenesis in Tg (HuC:egfp) zebrafish, motor neuron axon length in Tg (hb9:egfp) zebrafish, and downregulation of neurodevelopmental genes (elavl3, ngn1, gap43, gfap and mbp). In addition, DIF elevated oxidative stress by accumulation of reactive oxygen species (ROS) and inhibition of antioxidant enzymes, and triggered apoptosis by upregulation of p53, bax, bcl-2 and caspase-3, which were markedly intensified in the presence of n-TiO2. Moreover, vitamin C (VC) ameliorated n-TiO2/DIF-induced abnormal locomotor behaviors and neurotoxicity by inhibiting oxidative stress and apoptosis, indicating that oxidative stress and apoptosis are involved in n-TiO2/DIF-induced neurotoxicity. Taken together, our data indicated that n-TiO2 enhanced the accumulation of DIF and heightened oxidative stress and apoptosis, thereby inducing neurotoxicity. This study exemplifies the importance of the toxicity assessment of chemical mixtures and novel insights to mitigate their combined toxicity.

Human milk-derived extracellular vesicles alleviate high fat diet-induced non-alcoholic fatty liver disease in mice.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD), characterized by excessive hepatic lipid accumulation, imposes serious challenges on public health worldwide. Breastfeeding has been reported to reduce the risk of NAFLD. Extracellular vesicles (EVs) are bilayer membrane vesicles released from various cells into the extracellular space, participating in multiple life processes. Whether EVs from human milk exert metabolic benefits against NAFLD is worth investigating. METHODS AND RESULTS: In this study, the EVs were isolated from human milk collected from healthy mothers and quantified. Functional analyses were performed using the NAFLD mouse model and free fatty acid (FFA)-stimulated mouse primary hepatocytes. The results showed that human milk-derived EVs could effectively alleviate high fat diet-induced hepatic steatosis and insulin resistance in mice with NAFLD via inhibiting lipogenesis and increasing lipolysis. The FFA-induced lipid accumulation was also inhibited in hepatocytes after treatment with human milk-derived EVs. Mechanistically, the human milk derived-EVs cargo (proteins and miRNAs), which linked to lipid metabolism, may be responsible for these beneficial effects. CONCLUSION: The findings of this study highlighted the therapeutic benefits of human milk-derived EVs and provided a new strategy for NAFLD treatment.

Development, Reliability, and Validity of the Preschool Learning Skills Scale: A Tool for Early Identification of Preschoolers at Risk of Learning Disorder in Mainland China.

Background: Early identification of children at risk of learning disorders (LD) may mitigate the adverse effects of delayed intervention by guiding children to receive preventive services at an earlier age. However, there is no assessment tool for the early identification of children at risk of LD in Mainland China. Therefore, this study aimed to create a Chinese version of the Preschool Learning Skills Scale and investigate its validity and reliability. Methods: Firstly, a pilot scale was designed based on literature review and expert review. Secondly, a pre-survey of the pilot scale was conducted. In phase 3, a formal survey was carried out to test the reliability and validity of the scale by involving 2,677 preschool children from 7 kindergartens. Data were collected using a checklist for demographic characteristics, the preschool learning skills scale, the Behavior Rating Inventory of Executive Function-Preschool Version (BRIEF-P), and Conners' Rating Scales. Results: The final scale included 38 items under seven factors. The reliability and validity tests confirmed that the Cronbach's alpha, split-half reliability, and test-retest reliability coefficients of the scale were 0.946, 0.888, and 0.941, respectively. The Spearman correlations of factor-total score ranged from 0.685 to 0.876. The results of criterion-related validity showed a direct and significant association between the preschool learning skills scale with the BRIEF-P (r = 0.641, P < 0.001) and the cognitive problems factor of Conners' Rating Scales (r = 0.564, P < 0.001). The model had a good fit (χ 2 /df = 3.489, RMSEA = 0.047, RMR = 0.024, CFI = 0.912, TLI = 0.900, and IFI = 0.912). Multigroup confirmatory factor analysis supported the structural and measurement invariance on the preschool learning skills scale across gender and grade. Conclusions: The developed preschool learning skills scale has good reliability and validity, indicating that the scale can be used to identify preschool children at risk of LD and can be recommended for use in clinical research and practice.

Association of Maternal Mild Hypothyroidism With Offspring Neurodevelopment in TPOAb-Negative Women: A Prospective Cohort Study.

Objectives: Adequate maternal thyroid hormone availability is crucial for fetal neurodevelopment, but the role of maternal mild hypothyroidism is not clear. We aim to investigate the association of maternal mild hypothyroidism with neurodevelopment in infants at 1 year of age among TPOAb-negative women. Methods: The present study was conducted within the Jiangsu Birth Cohort. A total of 793 mother-infant pairs were eligible for the present study. Maternal thyroid function was assessed by measuring serum thyroid-stimulating hormone, free thyroxine, and thyroid peroxidase antibodies. Neurodevelopment of infants was assessed by using the Bayley Scales of Infant and Toddler Development third edition screening test (Bayley-III screening test). Results: In the multivariate adjusted linear regression analyses, infants of women with subclinical hypothyroidism and isolated hypothyroxinemia were associated with decreased receptive communication scores (ß = -0.68, p = 0.034) and decreased gross motor scores (ß = -0.83, p = 0.008), respectively. Moreover, infants of women with high-normal TSH concentrations (3.0-4.0 mIU/L) and low FT4 concentrations were significantly associated with lower gross motor scores (ß = -1.19, p = 0.032), while no differences were observed in infants when the mothers had a high-normal TSH concentration and normal FT4 levels. Conclusions: Maternal subclinical hypothyroidism is associated with decreased receptive communication scores in infants at 1 year of age. In addition, maternal TSH concentration greater than 4.0 mIU/L and maternal isolated hypothyroxinemia are associated with impaired gross motor ability of infants, especially in infants of women with high-normal TSH concentrations (3.0-4.0 mIU/L).

Development and Evaluation of Orthographic Knowledge Awareness Scale for Children Aged 6-12 Years.

Objective: This study primarily aimed to develop an orthographic knowledge awareness scale in Mandarin for children aged 6-12 years. Related factors affecting orthographic knowledge awareness in children were analyzed, and a basis for individualized intervention was provided to improve reading and writing. Methods: A conceptual framework for orthographic knowledge awareness in children aged 6-12 years was determined through a detailed reading of the literature on Chinese character orthography, combined with qualitative interviews of the target population and consultation with experts. The orthographic knowledge awareness scale initially consisted of three versions: for grades 1-2 (210 items), grades 3-4 (207 items), and grades 5-6 (220 items), accumulating a total of 637 items. The initial scale was then used for the study involving children aged 6-12 years in Maanshan City, Jiangsu Province. Various approaches to screening items were comprehensively used to determine the formal version of the orthographic knowledge awareness scale. The official scale was ultimately used to conduct the third round of surveys among 1,354 children aged 6-12 years in ordinary primary schools located in 5 cities in Jiangsu Province, namely, Changzhou, Lianyungang, Nantong, Xuzhou, and Yangzhou. The reliability, validity, and discriminating power of the formal scale were evaluated. Results: A total of 360 items were included in the formal version of the orthographic knowledge awareness scale. The formal scale was divided into three versions for grades 1-2, 3-4, and 5-6. Each grade version consisted of 120 items. The scale was composed of the stroke awareness test, radical awareness test, and left-right reversal test. The cumulative variance contribution rates of grades 1-2, 3-4, and 5-6 were 82.47, 61.71, and 64.19%, respectively. The Cronbach's α coefficients of the three-grade version of the scale were 0.989, 0.946, and 0.938; the split-half reliability coefficients were 0.925, 0.766, and 0.847; and the test-retest reliability coefficients were 0.847, 0.895, and 0.8928, respectively. Conclusion: The proposed orthographic knowledge awareness scale for children aged 6-12 years exhibits good reliability and validity. The formal scale consisted of two dimensions: identification of left-right reversal at the stroke and radical levels and the left-right reversal at the whole character level. The two dimensions can more comprehensively reflect the ability of children to discriminate orthographic structures.

Associations between antenatal corticosteroid exposure and neurodevelopment in infants.

BACKGROUND: It has been well recognized that antenatal administration of dexamethasone to pregnant women at risk of preterm delivery may markedly accelerate fetal maturation and reduce the risk of adverse perinatal outcomes in their preterm infants, particularly for births before 34 weeks of gestation. Since 2015, antenatal corticosteroid administration has been extended beyond 34 weeks of gestation by clinical guidelines, as it might have beneficial effects on fetal maturation and perinatal outcomes. However, concerns regarding the potential influence of antenatal corticosteroid treatment on offspring neurodevelopment have been raised. OBJECTIVE: This study aimed to investigate whether maternal antenatal corticosteroid administration was associated with neurodevelopment in infants at 1 year of age. STUDY DESIGN: In this prospective and longitudinal birth cohort study, women were followed up throughout gestation, and their infants underwent a Bayley Scales of Infant and Toddler Development, Third Edition, screening test at 1 year of age between December 2018 and September 2020. Finally, 1609 pregnant women and 1759 infants were included in the current study. Using a generalized linear mixed model, we examined the association between antenatal corticosteroid exposure and infant neurodevelopment in cognitive, receptive communication, expressive communication, fine motor, and gross motor functions. RESULTS: Of the 1759 infants eligible for this study, 1453 (82.6%) were singletons. A total of 710 infants were exposed to antenatal corticosteroids, among whom 415 were dexamethasone exposed and 483 were prednisone exposed. Dexamethasone was prescribed most often in late pregnancy, whereas prednisone was often used before 8 weeks of gestation among women who conceived through assisted reproductive technology. Compared with those who had no exposure, antenatal corticosteroid exposure was associated with an increased risk of infants being noncompetent in the cognitive development domain after adjusting for conventional risk factors (adjusted risk ratio, 1.53; 95% confidence interval, 1.08-2.18; P=.017). For medication-specific exposure, those exposed vs not exposed to antenatal dexamethasone were 1.62-fold (95% confidence interval, 1.10-2.38; P=.014) more likely to be noncompetent in the cognitive development domain at 1 year. The association did not vary markedly between preterm and term infants, singletons and twins, or assisted reproductive technology-conceived and spontaneously conceived infants (all P>.05 for heterogeneity). In contrast, a null association was observed for the risk of being noncompetent in any domain of neurodevelopment with antenatal prednisone exposure at early pregnancy. CONCLUSION: Here, antenatal corticosteroid, particularly dexamethasone exposure, was markedly associated with an increased risk of infants being noncompetent in the cognitive development domain at 1 year of age. These findings may provide new information when weighing the benefits and potential risks of maternal antenatal corticosteroid administration.

The development, validity, reliability, and norm of a preschool auditory processing assessment scale in China.

BACKGROUND: Children with auditory processing deficits may face problems with language, learning, and social communication. AIMS: To develop a Chinese auditory processing assessment scale for preschool children and establish the norms of the scale. METHODS AND PROCEDURES: The predictive version of the scale was formed by a literature review, qualitative interviews, expert consultation, and a pre-test with a small sample. Nine kindergartens in Nanjing were selected by a stratified cluster sampling plan. First, 734 children from two kindergartens were selected for the large sample pre-test of the scale. Then, 1526 children from four kindergartens and 1151 children from three kindergartens were selected for the reliability and validity analysis and confirmatory factor analysis, respectively. The standardized norm data of the scale were established based on the 3411 points of scale data of the nine kindergartens. Finally, the clinical usefulness of the scale was analyzed by comparing the results of objective auditory processing tests in children with normal and abnormal auditory processing prompted by the score on the scale. OUTCOMES AND RESULTS: The preschool auditory processing assessment scale includes 5 dimensions and 30 items. The Cronbach's alpha value of the scale is greater than 0.9. The confirmatory factor analysis results verify that the scale structure is reasonable. The percentile norm of the scale was established. The results of electrophysiological tests of the normal and abnormal auditory processing groups were statistically different (P < 0.05). CONCLUSIONS AND IMPLICATIONS: The developed preschool auditory processing assessment scale has good reliability and validity. The scale is suitable for clinical application.

Development and Validation of a Novel Diagnostic Model for Childhood Autism Spectrum Disorder Based on Ferroptosis-Related Genes.

Autism spectrum disorder (ASD) is a highly genetic heterogeneous neurodevelopmental disorder, which is usually considered a heritable and heterogeneous neurodevelopmental disorder and has caused a great burden to society and families. Emerging roles of ferroptosis have been observed in neurological disorders. This study aimed to construct a diagnostic model based on ferroptosis-related genes (FRGs) to contribute to the early and precise diagnosis of childhood ASD. In the candidate FRGs, we identified 27 differentially expressed genes (DEGs) between ASD patients and typically developing (TD) controls. Four key FRGs were identified using the random forest analysis for further analysis. Utilization of the four gene expression, we constructed a diagnostic model and the AUC value in the training dataset (GSE18123) is 0.7002. We deem that a patient with a score less than 0.9904 is likely to have ASD. Three validation datasets (GSE111176, GSE113834, and GSE28521) were collected and the AUC value is 0.7442, 0.7444, and 0.6474, respectively. A multi-factor regulatory network based on four FRGs indicated that RORA, EAF1, NFYB, miR-4703-3p, and miR-6073 may play a role in the development of ASD. In addition, we found piperaquine may have the potential to be a promising drug for the treatment of ASD. Overall, we constructed a diagnostic model of childhood ASD, which could contribute to the precision diagnosis and timely treatment of childhood ASD.

Comparison of different neonatal illness severity scores in predicting mortality risk of extremely low birth weight infants.

To compare different illness severity scores in predicting mortality risk of extremely low birth weight infants (ELBWI). From January 1st, 2019 to January 1st, 2020, all ELBWI admitted in the Children's Hospital of Nanjing Medical University, Nanjing Maternity and Child Health Care Hospital and the First Affiliated Hospital of Nanjing Medical University were included in the study. ELBWI with admission age ≥1 h, gestational age ≥37 weeks and incomplete data required for scoring were excluded. The clinical data were collected, neonatal critical illness score (NCIS), score for neonatal acute physiology version Ⅱ (SNAP-Ⅱ), simplified version of the score for neonatal acute physiology perinatal extension (SNAPPE-Ⅱ), clinical risk index for babies (CRIB) and CRIB-Ⅱ were calculated. The scores of the fatal group and the survival group were compared, and the receiver operating characteristic (ROC) curve was used to evaluate the predictive value of the above illness severity scores for the mortality risk of ELBWI. Pearson correlation analysis was used to analyze the correlation between illness scores and birth weight, illness scores and gestational age. A total of 192 ELBWI were finally included, of whom 114 cases survived (survival group) and 78 cases died (fatal group). There were significant differences in birth weight, gestational age and Apgar scores between fatal group and survival group (all <0.01). There were significant differences in NCIS, SNAP-Ⅱ, SNAPPE-Ⅱ, CRIB and CRIB-Ⅱ between fatal group and survival group (all <0.01). The CRIB had a relatively higher predictive value for the mortality risk. Its area under the ROC curve (AUC) was 0.787, the sensitivity was 0.678, the specificity was 0.804, and the Youden index was 0.482. The scores of NCIS, SNAP-Ⅱ, SNAPPE-Ⅱ, CRIB and CRIB-Ⅱ were significantly correlated with birth weight and gestational age (all <0.05). The correlation coefficients of CRIB-Ⅱ and CRIB with birth weight and gestational age were relatively large, and the correlations coefficients of NCIS with birth weight and gestational age were the smallest (0.191 and 0.244, respectively). Among these five illness severity scores, CRIB has better predictive value for the mortality risk in ELBWI. NCIS, which is widely used in China, has relatively lower sensitivity and specificity, and needs to be further revised.