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Autism spectrum disorder (ASD) is a neurodevelopmental disorder with high genetic heritability but heterogeneity. Fully understanding its genetics requires whole-genome sequencing (WGS), but the ASD studies utilizing WGS data in Chinese population are limited. In this study, we present a WGS study for 334 individuals, including 112 ASD patients and their non-ASD parents. We identified 146 de novo variants in coding regions in 85 cases and 60 inherited variants in coding regions. By integrating these variants with an association model, we identified 33 potential risk genes (P<0.001) enriched in neuron and regulation related biological process. Besides the well-known ASD genes (SCN2A, NF1, SHANK3, CHD8 etc.), several high confidence genes were highlighted by a series of functional analyses, including CTNND1, DGKZ, LRP1, DDN, ZNF483, NR4A2, SMAD6, INTS1, and MRPL12, with more supported evidence from GO enrichment, expression and network analysis. We also integrated RNA-seq data to analyze the effect of the variants on the gene expression and found 12 genes in the individuals with the related variants had relatively biased expression. We further presented the clinical phenotypes of the proband carrying the risk genes in both our samples and Caucasian samples to show the effect of the risk genes on phenotype. Regarding variants in non-coding regions, a total of 74 de novo variants and 30 inherited variants were predicted as pathogenic with high confidence, which were mapped to specific genes or regulatory features. The number of de novo variants found in patient was significantly associated with the parents' ages at the birth of the child, and gender with trend. We also identified small de novo structural variants in ASD trios. The results in this study provided important evidence for understanding the genetic mechanism of ASD.
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Background: Intramuscular (IM) injection of penicillin G Benzathine (PGB) is widely recognized as the primary treatment for patients at all stages of syphilis. However, the discomfort and induration associated with PGB injections are often a challenge for patients. While lidocaine is already known to reduce injection pain and is standard practice in some countries, the added value of combining lidocaine with the z-track technique has not been thoroughly investigated. This study aims to observe the use of combining lidocaine with the Z-track technique in the treatment of syphilis, and to explore less painful methods of administering IM PGB for the treatment of syphilis in adult patients. Methods: 32 syphilis patients requiring penicillin treatment were injected with 1.2 million units of penicillin on both sides of the buttocks. The left side was injected using the traditional method with 0.9% saline as the solvent (control Group), while the right side was injected using a "z" injection method with 0.2% lidocaine as the solvent (experimental Group). The success rate of the single injection, the intensity and duration of the post-injection pain and the induration reaction were observed and recorded. Results: There was no statistically significant difference in single injection success rate and immediate post injection pain score between the two sides (P>0.05). However, the right side had a lower pain score at 30 minutes post injection and fewer induration reactions, showing a statistically significant difference between the two sides (P<0.05). Chi-squared analysis showed that age, gender and BMI had no significant effect on pain scores 30 minutes after injection in either the control or intervention groups. (P>0.05). Conclusion: The lidocaine + Z-track penicillin method can reduce delayed pain and induration reactions in patients with syphilis, and provides an additional approach to improving patient comfort beyond the standard use of lidocaine alone. This method merits clinical promotion.
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A 10-year-old boy presented with persistent genital erythematous plaques unresponsive to traditional topical treatments. Apremilast, an underexplored option in pediatric cases, was initiated and resulted in a significant reduction in pruritus and resolution of the lesions. This case provides insight into the potential efficacy of apremilast in refractory pediatric inverse psoriasis and underscores the necessity for further research in this specific population.
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Background: As vitiligo progresses, autophagy becomes more and more important. Objectives: To validate potential genes associated with autophagy in vitiligo through bioinformatics analysis and experimental testing. Materials and Methods: Dataset GSE75819 of mRNA expression profiles was obtained from GEO. After data normalisation, gene set enrichment analyse enrichment analysis and abundance analysis of infiltrating immune cells were performed. A list of autophagy-related differentially expressed genes (ARDEGs) associated with vitiligo was generated using R software. Protein-protein interaction (PPI) analysis, correlation analysis, and enrichment analysis on gene ontology (GO) and Kyoto encyclopaedia of genes and genome (KEGG) pathways were conducted on the ARDEG data. The microRNAs associated with hub genes were predicted using the TargetScan database. Finally, RNA expression of 10 hub genes and Western blotting (WB) of autophagy pathway factors were further verified. Results: From the lesions of 15 vitiligo patients, 44 ARDEGs were identified. PPI analysis demonstrated that these ARDEGs interacted with each other. GO and KEGG analyses of ARDEGs revealed that several enriched terms were associated with macroautophagy (biological process), vacuolar membranes (cellular components), cysteine-type peptidase activity (molecular function), and autophagy in animals, neurodegeneration-multiple disease pathways, and apoptosis. In vitiligo lesions, qRT-PCR and sequencing validation analyses showed expression levels of CCL2, RB1CC1, TP53, and ATG9A that were consistent with bioinformatic analysis of the microarray. WB results also showed that autophagy-related proteins were differentially expressed. Conclusions: Forty-four potential ARDEGs were identified in vitiligo by bioinformatic analysis. Vitiligo may be affected by autophagy regulation through CCL2, RB1CC1, TP53, and ATG9A.
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Objective: ALA-PDT (5-aminolevulinic acid photodynamic therapy) is a central modality in the treatment of skin diseases. Increasing the bioavailability of ALA remains a critical issue. With this in mind, our study explores a novel route of ALA delivery by loading acrylic nanoparticles (ANPs). Methods: ALA-ANPs were synthesized by emulsion polymerisation and characterised by scanning electron microscopy (SEM), transmission electron microscopy (TEM) and nanoparticle tracking analysis (NTA). The effects of ALA-ANPs on HaCaT cell line were evaluated, including characteristics, morphological changes, protoporphyrin IX (PpIX) fluorescence kinetics, reactive oxygen species (ROS) levels, mitochondrial membrane potential and ki67 expression in these cells. Results: The ANPs had uniform sizes, smooth surfaces and excellent light transmittance, with diameters of 150-200 nm. In contrast, the ALA - ANPs had uneven surfaces and poor light transmittance, with diameters of 220-250 nm. During 12 hours of co-incubation of HaCaT cells with ALA, the intracellular accumulation of PpIX increased over time. Notably, after 6 hours of incubation, PpIX levels induced by 1.81 mg/mL ALA-ANPs exceeded those induced by 1.0 mM ALA (p < 0.01). CCK-8 results showed a positive correlation between PDT-induced inhibition of HaCaT cell proliferation and ALA concentration when ALA concentration remained below 2.0 mM. Compared to the 1.0 mM ALA group, the 1.81 mg/mL ALA-ANPs group showed decreased mitochondrial membrane potential, ki67 immunofluorescence intensity and cell proliferation. In contrast, ROS levels were significantly increased in the 1.81 mg/mL ALA-ANPs group (p < 0.01). Conclusion: Loading ANPs provide improved stability and potency for ALA. The ALA-ANPs-PDT approach has superior inhibitory effects on HaCaT proliferation in vitro.
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Cumulative evidence has showed the deficits of inhibitory control in patients with attention deficit hyperactivity disorder (ADHD), which is considered as an endophenotype of ADHD. Genetic study of inhibitory control could advance gene discovery and further facilitate the understanding of ADHD genetic basis, but the studies were limited in both the general population and ADHD patients. To reveal genetic risk variants of inhibitory control and its potential genetic relationship with ADHD, we conducted genome-wide association studies (GWAS) on inhibitory control using three datasets, which included 783 and 957 ADHD patients and 1350 healthy children. Subsequently, we employed polygenic risk scores (PRS) to explore the association of inhibitory control with ADHD and related psychiatric disorders. Firstly, we identified three significant loci for inhibitory control in the healthy dataset, two loci in the case dataset, and one locus in the meta-analysis of three datasets. Besides, we found more risk genes and variants by applying transcriptome-wide association study (TWAS) and conditional FDR method. Then, we constructed a network by connecting the genes identified in our study, leading to the identification of several vital genes. Lastly, we identified a potential relationship between inhibitory control and ADHD and autism by PRS analysis and found the direct and mediated contribution of the identified genetic loci on ADHD symptoms by mediation analysis. In conclusion, we revealed some genetic risk variants associated with inhibitory control and elucidated the benefit of inhibitory control as an endophenotype, providing valuable insights into the mechanisms underlying ADHD.
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Transtorno do Deficit de Atenção com Hiperatividade , Criança , Humanos , Transtorno do Deficit de Atenção com Hiperatividade/psicologia , Estudo de Associação Genômica Ampla , Predisposição Genética para Doença/genética , Loci Gênicos , Fatores de Risco , Estratificação de Risco GenéticoRESUMO
Chemoselective protein modification plays extremely important roles in various biological, medical, and pharmaceutical investigations. Mimicking the mechanism of the chemoselective reaction between natural azaphilones and primary amines, this work successfully simplified the azaphilone scaffold into much simpler 3-acyl-4-pyranones. Examinations confirmed that these slim-size mimics perfectly kept the unique reactivity for selective conjugation with the primary amines including lysine residues of peptides and proteins. The newly developed pyranone tool presents remarkably increased aqueous solubility and compatible second-order rate constant by comparison with the original azaphilone. Additional advantages also include the ease of biorthogonal combinative use with a copper-catalyzed azide-alkyne Click reaction, which was conveniently applied to decorate lysozyme with neutral-, positive- and negative-charged functionalities in parallel. Moderate-degree modification of lysozyme with positively charged quaternary ammoniums was revealed to increase the enzymatic activities.
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Lisina , Muramidase , Lisina/química , Indicadores e Reagentes , Peptídeos/química , Aminas , Azidas/química , Química Click , Alcinos/químicaRESUMO
OBJECTIVE: Although ADHD is highly heritable, some environmental factors contribute to its development. Given the growing evidence that gut microbiota was involved in psychiatric disorders, we aimed to identify the characteristic composition of the gut microbiota in ADHD. METHODS: We recruited 47 medication-naive children and adolescents with ADHD, and 60 healthy controls (HCs). We used shotgun metagenomics to measure the structure of the gut microbiota and analyzed the difference in bacterial taxa between ADHD and HCs. RESULTS: Significant differences were found between the ADHD and HC groups in both alpha diversity indices (Simpson index, p = .025 and Shannon index, p = .049) and beta diversity indices (Euclidean distance, Bray-Curtis distance, and JSD distance, p < 2.2e-16). Nine representative species best explain the difference. CONCLUSION: Patients with ADHD showed significant differences in the composition of the gut microbiota compared with HCs. These results may help identify potential biomarkers of ADHD.
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Transtorno do Deficit de Atenção com Hiperatividade , Microbioma Gastrointestinal , Adolescente , Criança , Humanos , Microbioma Gastrointestinal/genéticaRESUMO
Objective: To identify potential diagnostic markers for vitiligo and determine the significance of immune cell infiltration in pathology. Methods: Three publicly available gene expression profiles (GSE53146, GSE75819 and GSE65127 datasets) from human vitiligo and control samples were downloaded from the GEO database. Differentially expressed genes (DEGs) were screened between 20 vitiligo and 20 control samples. Logical regression of the selection operator (LASSO) model and support vector machine recursive feature elimination (SVM-RFE) analysis were performed to identify candidate biomarkers. The area under the receiver operating characteristic curve (AUC) value was obtained and was used to evaluate the discriminatory ability. The expression level and diagnostic value of the biomarkers in vitiligo were further validated in the GSE65127 dataset (10 vitiligo patients and 10 healthy controls). Finally, the immune cell infiltration of vitiligo was evaluated by CIBERSORT, and the correlation between biomarkers and infiltrating immune cells was analyzed. The compositional patterns of the 22 types of immune cell fractions in vitiligo were estimated from the pooled cohorts using CIBERSORT. In addition, we established a mouse model of vitiligo with monobenzone and validated the screened biomarkers. Results: A total of 23 associated DEGs were identified, including 9 up-regulated and 14 down-regulated genes. Subsequently, 17 genes meeting prognostic criteria and 2 common genes (DCT and KIF1A) were obtained by SVM and Venn diagram screening. Immunodifferential analysis showed that microenvironment of vitiligo patients was altered. Finally, the different expression was verified by polymerase chain reaction (PCR). Conclusion: Biomarkers associated with vitiligo can be screened by comprehensive strategies, and immune cell infiltration plays a key role in the development of vitiligo.
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OBJECTIVE: Working memory (WM) deficits have frequently been linked to attention deficit hyperactivity disorder (ADHD). Despite previous studies suggested its high heritability, its genetic basis, especially in ADHD, remains unclear. The current study aimed to comprehensively explore the genetic basis of visual-spatial working memory (VSWM) in ADHD using wide-ranging genetic analyses. METHODS: The current study recruited a cohort consisted of 802 ADHD individuals, all met DSM-IV ADHD diagnostic criteria. VSWM was assessed by Rey-Osterrieth complex figure test (RCFT), which is a widely used psychological test include four memory indexes: detail delayed (DD), structure delayed (SD), structure immediate (SI), detail immediate (DI). Genetic analyses were conducted at the single nucleotide polymorphism (SNP), gene, pathway, polygenic and protein network levels. Polygenic Risk Scores (PRS) were based on summary statistics of various psychiatric disorders, including ADHD, autism spectrum disorder (ASD), major depressive disorder (MDD), schizophrenia (SCZ), obsessive compulsive disorders (OCD), and substance use disorder (SUD). RESULTS: Analyses at the single-marker level did not yield significant results (5E-08). However, the potential signals with P values less than E-05 and their mapped genes suggested the regulation of VSWM involved both ocular and neural system related genes, moreover, ADHD-related genes were also involved. The gene-based analysis found RAB11FIP1, whose encoded protein modulates several neurodevelopment processes and visual system, as significantly associated with DD scores (P = 1.96E-06, Padj = 0.036). Candidate pathway enrichment analyses (N = 53) found that forebrain neuron fate commitment significantly enriched in DD (P = 4.78E-04, Padj = 0.025), and dopamine transport enriched in SD (P = 5.90E-04, Padj = 0.031). We also observed a significant negative relationship between DD scores and ADHD PRS scores (P = 0.0025, Empirical P = 0.048). CONCLUSIONS: Our results emphasized the joint contribution of ocular and neural genes in regulating VSWM. The study reveals a shared genetic basis between ADHD and VSWM, with GWAS indicating the involvement of ADHD-related genes in VSWM. Additionally, the PRS analysis identifies a significant relationship between ADHD-PRS and DD scores. Overall, our findings shed light on the genetic basis of VSWM deficits in ADHD, and may have important implications for future research and clinical practice.
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Transtorno do Deficit de Atenção com Hiperatividade , Transtorno do Espectro Autista , Transtorno Depressivo Maior , Criança , Humanos , Memória de Curto Prazo , Olho , Transtornos da MemóriaRESUMO
INTRODUCTION: Preterm (PT) infants are at high likelihood for poor neurodevelopmental outcomes, including autism spectrum disorder (ASD), attention-deficit hyperactivity disorder (ADHD) and other neurodevelopmental disorders (NDDs), which could considerably impair the individuals' functions throughout their whole life. The current cohort study aims to investigate adverse outcomes, especially NDDs, in PT children, and the related early aberrant brain developmental biomarkers. METHODS AND ANALYSIS: This is a prospective cohort study in Beijing, China. We plan to recruit 400 PT infants born at <37 weeks of gestational age (GA), and 200 full-term (FT) controls during the neonatal period (40 weeks corrected GA), then follow them up until they reach 6 years of age. This cohort is designed to assess neuropsychological functions, brain development, related environmental risk factors and the incidence of NDDs by using the following measures: (1) social, emotional, cognitive and sensorimotor functions; (2) MRI, electroencephalogram and functional near-infrared spectroscopy; (3) social economic status, maternal mental health and DNA methylation; and (4) symptoms and diagnosis of NDDs. Main data analyses will include comparing the neurodevelopment outcomes and brain developmental trajectories between PT and FT children using linear or logistic regressions and mixed-effects models. Regression analyses and machine learning will be used to identify early biological predictors and environmental risk or protective factors for later NDDs outcomes. ETHICS AND DISSEMINATION: Ethical approval has been obtained from the research ethics committee of Peking University Third Hospital (M2021087). This study is under review in the Chinese Clinical Trial Register. The study results from the current cohort will be disseminated and popularised through social media to participating parents, as well as parents who are giving care to PT children.
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Transtorno do Espectro Autista , Transtornos do Neurodesenvolvimento , Criança , Humanos , Lactente , Recém-Nascido , Transtorno do Espectro Autista/complicações , Biomarcadores , Estudos de Coortes , Recém-Nascido Prematuro , Estudos Longitudinais , Transtornos do Neurodesenvolvimento/epidemiologia , Estudos Prospectivos , Pré-EscolarRESUMO
Background: Social deficits are among the most important functional impairments in attention-deficit/hyperactivity disorder (ADHD). However, the relationship between social impairment and ADHD core symptoms as well as the underlying cerebral blood flow (CBF) characteristics remain unclear. Methods: A total of 62 ADHD subjects with social deficits (ADHD + SD), 100 ADHD subjects without social deficits (ADHD-SD) and 81 age-matched typically developing controls (TDC) were enrolled. We first examined the correlation between the Social Responsiveness Scale (SRS-1) and ADHD core symptoms (inattention, hyperactivity, and impulsion) and then explored categorical and dimensional ADHD-related regional CBF by arterial spin labeling (ASL). For the categorical analysis, a voxel-based comparison of CBF maps between the ADHD + SD, ADHD-SD, and TDC groups was performed. For the dimensional analysis, the whole-brain voxel-wise correlation between CBF and ADHD symptoms (inattention, hyperactivity/impulsivity, and total scores) was evaluated in three groups. Finally, correlations between the SRS-1 and ADHD-related regional CBF were investigated. We applied Gaussian random field (GRF) for the correction of multiple comparisons in imaging results (voxel-level P < 0.01, and cluster-level P < 0.05). Results: The clinical characteristics analysis showed that social deficits positively correlated with ADHD core symptoms, especially in social communication and autistic mannerisms domains. In the categorical analysis, we found that CBF in the left middle/inferior temporal gyrus in ADHD groups was higher than TDCs and was negatively correlated with the social motivation scores. Moreover, in dimensional analysis, we found that CBF in the left middle frontal gyrus was negatively correlated with the inattention scores, SRS total scores and autistic mannerisms scores in ADHD + SD subjects. Conclusion: The present study shows that inattention, hyperactivity, and impulsivity may be responsible for the occurrence of social deficits in ADHD, with autistic traits being another significant contributing factor. Additionally, CBF in the left middle/inferior temporal gyrus and the left middle frontal gyrus might represent the corresponding physiological mechanisms underlying social deficits in ADHD.
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Controlling the optical properties of metal plasma nanomaterials through structure manipulation has attracted great attention for solar steam generation. However, realizing broadband solar absorption for high-efficiency vapor generation is still challenging. In this work, a free-standing ultralight gold film/foam with a hierarchical porous microstructure and high porosity is obtained through controllably etching a designed cold-rolled (NiCoFeCr)99Au1 high-entropy precursor alloy with a unique grain texture. During chemical dealloying, the high-entropy precursor went through anisotropic contraction, resulting in a larger surface area compared with that from the Cu99Au1 precursor although the volume shrinkage is similar (over 85%), which is beneficial for the photothermal conversion. The low Au content also results in a special hierarchical lamellar microstructure with both micropores and nanopores within each lamella, which significantly broadens the optical absorption range and makes the optical absorption of the porous film reach 71.1-94.6% between 250 and 2500 nm. In addition, the free-standing nanoporous gold film has excellent hydrophilicity, with the contact angle reaching zero within 2.2 s. Thus, the 28 h dealloyed nanoporous gold film (NPG-28) exhibits a rapid evaporation rate of seawater under 1 kW m-2 light intensity, reaching 1.53 kg m-2 h-1, and the photothermal conversion efficiency reaches 96.28%. This work demonstrates the enhanced noble metal gold using efficiency and solar thermal conversion efficiency by controlled anisotropic shrinkage and forming a hierarchical porous foam.
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Attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) show common brain area abnormalities, which may contribute to the high shared co-occurrence symptoms and comorbidity of the two disorders. However, neuroanatomic anomalies in neurodevelopmental disorders may change over the course of development, and the developmental variation of these two disorders is unclear. Our study conducted a systematic literature search of PubMed, Web of Science, and EMBASE databases to identify disorder-shared abnormalities of white matter (WM) from childhood to adulthood in ADHD and ASD. 28 ADHD and 23 ASD datasets were included in this meta-analysis and were analysed by AES-SDM to detect differences in fractional anisotropy in patients compared to typically developing individuals. Our main findings reveal the variable WM developmental trajectories in ADHD and ASD respectively, and the two disorders showed overlapping corpus callosum tract abnormalities in their development from children to adults. Furthermore, the overlapping abnormalities of the corpus callosum tract increased with age, which may be related to their gradually increasing shared symptoms and comorbidity in these two disorders.
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Transtorno do Deficit de Atenção com Hiperatividade , Transtorno do Espectro Autista , Substância Branca , Criança , Adulto , Humanos , Adolescente , Adulto Jovem , Imagem de Tensor de Difusão , Substância Branca/diagnóstico por imagem , Transtorno do Espectro Autista/diagnóstico por imagem , Transtorno do Espectro Autista/epidemiologia , Transtorno do Deficit de Atenção com Hiperatividade/diagnóstico por imagem , Transtorno do Deficit de Atenção com Hiperatividade/epidemiologia , Corpo CalosoRESUMO
An 11-step enantioselective total synthesis of (+)-sieboldine A (1) has been accomplished from (5R)-methylcyclohex-2-en-1-one (16), in which an intramolecular ketone/ester reductive coupling followed by one-pot acidic treatment to quickly construct the unique oxa-spiroacetal and a TsOH-catalyzed displacement to directly form the characteristic N-hydroxyazacyclononane ring successfully served as the key methodologies. Moreover, several full-skeleton analogues of 1 were also synthesized on the basis of the advanced intermediates, and their inhibitory effects on electric eel acetylcholinesterase were examined.
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Acetilcolinesterase , Cetonas , Estereoisomerismo , ÉsteresRESUMO
Nanoparticle strengthening provides a crucial basis for developing high-performance structural materials with potentially superb mechanical properties for structural applications. However, the general wisdom often fails to work well due to the poor thermal stability of nanoparticles, and the rapid coarsening of these particles will lead to the accelerated failures of these materials especially at elevated temperatures. Here, we demonstrate a strategy to achieve ultra-stable nanoparticles at 800~1000 °C in a Ni59.9-xCoxFe13Cr15Al6Ti6B0.1 (at.%) chemically complex alloy, resulting from the controllable sluggish lattice diffusion (SLD) effect. Our diffusion kinetic simulations reveal that the Co element leads to a significant reduction in the interdiffusion coefficients of all the main elements, especially for the Al element, with a maximum of up to 5 orders of magnitude. Utilizing first-principles calculations, we further unveil the incompressibility of Al induced by the increased concentration of Co plays a critical role in controlling the SLD effect. These findings are useful for providing advances in the design of novel structural alloys with extraordinary property-microstructure stability combinations for structural applications.
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BACKGROUND: Migration has been implicated as a risk factor for autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD), but evidence is still limited and inconsistent. We aim to investigate the relationship between migration status and risk of ASD and ADHD. METHODS: Electronic databases including PubMed, EMBASE, Web of Science, and PsychINFO were searched to identify observational studies on this topic, from inception to February 2021. Random-effects meta-analysis models were used to pool the summary odds ratio (OR) and 95% confidence interval (95% CI), and subgroup analyses were conducted to detect possible discrepancies in associations. Certainty of evidence was assessed as per the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) guidelines. RESULTS: A total of 13 studies (6,532,546 participants) for ASD, five studies (2,875,070 participants) for ADHD, and six studies (31,158 participants) for hyperactivity were included. Overall, the pooled results indicated that migration was associated with increased risk of ASD (pooled OR: 1.32; 95% CI: 1.07-1.63; P for Z test = 0.010), but no association was found between migration and ADHD (pooled OR: 0.84; 95% CI: 0.53-1.32; P for Z test = 0.452) or hyperactivity (pooled standardized mean difference: -0.073; 95% CIs: - 0.383-0.236; P for Z test = 0.642). Subgroup analyses further demonstrated that maternal migration was ASD risk factor (pooled OR: 1.49; 95% CI: 1.19-1.87), and migrant children were more likely to develop ASD with comorbid intellectual disability (ID) (pooled OR: 1.21, P for interaction = 0.006) than ASD without ID. After standardized the origin of migrants, European migrant children from Americas were at higher risk of ASD and ADHD (pooled OR were 4.13 and 1.26), and increased ASD risk was also observed in African children (pooled OR: 2.72). The GRADE of evidence was very low. CONCLUSIONS: Maternal migration is a risk factor for ASD, and migrant ASD children are more likely comorbid ID. The role of migration on ADHD remains controversial, more studies are needed to assess the association between migration status and ADHD. Health care practitioners should consider screening and providing extra resources for migrant children.
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Transtorno do Deficit de Atenção com Hiperatividade , Transtorno do Espectro Autista , Deficiência Intelectual , Transtorno do Deficit de Atenção com Hiperatividade/epidemiologia , Transtorno do Deficit de Atenção com Hiperatividade/etiologia , Transtorno do Espectro Autista/epidemiologia , Transtorno do Espectro Autista/etiologia , Criança , Comorbidade , Humanos , Deficiência Intelectual/epidemiologia , PrevalênciaRESUMO
BACKGROUND: Although methylphenidate (MPH) and atomoxetine (ATX) can improve clinical symptoms and functional impairments in attention deficit/hyperactive disorder (ADHD), the underlying psychopharmacological mechanisms have not been clearly elucidated. Therefore, we aimed to explore the shared and unique neurologic basis of these 2 medications in alleviating the clinical symptoms and functional impairments observed in ADHD. METHODS: Sixty-seven ADHD and 44 age-matched children with typical development were included and underwent resting-state functional magnetic resonance imaging scans at baseline. Then patients were assigned to MPH, ATX, or untreated subgroups, based on the patients' and their parents' choice, for a 12-week follow-up and underwent a second functional magnetic resonance imaging scan. The treatment effect on degree centrality (DC) was identified and correlated with clinical symptoms and functional impairments in the ADHD group. RESULTS: Both MPH and ATX normalized the DC value in extensive brain regions mainly involving fronto-cingulo-parieto-cerebellum circuits. However, ATX showed limited significant effects on the cerebellum compared with ADHD at baseline. The improvements in clinical symptoms were correlated with increased DC in the right inferior temporal gyrus in both MPH and ATX subgroups but showed opposite effects. The alleviation of functional impairments in the school/learning domain negatively correlated with decreased DC in the bilateral cerebellum after MPH treatment, and the family functional domain positively correlated with decreased DC in the cerebellum and negatively correlated with decreased DC in the postcentral gyrus after ATX treatment. CONCLUSIONS: Both MPH and ATX can normalize abnormal brain functions that mainly involve the fronto-cingulo-parieto-cerebellum circuit in ADHD. Furthermore, the 2 medications showed shared and unique effects on brain functions to alleviate clinical symptoms and functional impairment.
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Transtorno do Deficit de Atenção com Hiperatividade , Estimulantes do Sistema Nervoso Central , Metilfenidato , Inibidores da Captação Adrenérgica/uso terapêutico , Cloridrato de Atomoxetina/farmacologia , Cloridrato de Atomoxetina/uso terapêutico , Transtorno do Deficit de Atenção com Hiperatividade/diagnóstico por imagem , Transtorno do Deficit de Atenção com Hiperatividade/tratamento farmacológico , Encéfalo , Estimulantes do Sistema Nervoso Central/farmacologia , Criança , Humanos , Metilfenidato/farmacologiaRESUMO
Scaling up the production of cost-effective electrocatalysts for efficient water splitting at the industrial level is critically important to achieve carbon neutrality in our society. While noble-metal-based materials represent a high-performance benchmark with superb activities for hydrogen and oxygen evolution reactions, their high cost, poor scalability, and scarcity are major impediments to achieve widespread commercialization. Herein, a flexible freestanding Fe-based metallic glass (MG) with an atomic composition of Fe50Ni30P13C7 was prepared by a large-scale metallurgical technique that can be employed directly as a bifunctional electrode for water splitting. The surface hydroxylation process created unique structural and chemical heterogeneities in the presence of amorphous FeOOH and Ni2P as well as nanocrystalline Ni2P that offered various active sites to optimize each rate-determining step for water oxidation. The achieved overpotentials for the oxygen evolution reaction were 327 and 382 mV at high current densities of 100 and 500 mA cm-2 in alkaline media, respectively, and a cell voltage of 1.59 V was obtained when using the MG as both the anode and the cathode for overall water splitting at a current density of 10 mA cm-2. Theoretical calculations unveiled that amorphous FeOOH makes a significant contribution to water molecule adsorption and oxygen evolution processes, while the amorphous and nanocrystalline Ni2P stabilize the free energy of hydrogen protons (ΔGH*) in the hydrogen evolution process. This MG alloy design concept is expected to stimulate the discovery of many more high-performance catalytic materials that can be produced at an industrial scale with customized properties in the near future.
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BACKGROUND: Neurodevelopmental disorders (NDDs) usually present overlapping symptoms. Abnormal white matter (WM) microstructure has been found in these disorders. Identification of common and unique neural abnormalities across NDDs could provide further insight into the underlying pathophysiological mechanisms. METHODS: We performed a voxel-based meta-analysis of whole-brain diffusion tensor imaging (DTI) studies in autism spectrum disorder (ASD), attention-deficit/hyperactivity disorder (ADHD) and other NDDs. A systematic literature search was conducted through March 2020 to identify studies that compared measures of WM microstructure between patients with NDDs and neurotypical controls. Peak voxel coordinates were meta-analyzed via anisotropic effect size-signed differential mapping (AES-SDM) as well as activation likelihood estimation (ALE). RESULTS: Our final sample included a total of 4137 subjects from 66 studies across five NDDs. Fractional anisotropy (FA) reductions were found in the splenium of the CC in ADHD, and the genu and splenium of CC in ASD. And mean diffusivity (MD) increases were shown in posterior thalamic radiation in ASD. No consistent abnormalities were detected in specific learning disorder, motor disorder or communication disorder. Significant differences between child/adolescent and adult patients were found within the CC across NDDs, reflective of aberrant neurodevelopmental processes in NDDs. CONCLUSIONS: The current study demonstrated atypical WM patterns in ASD, ADHD and other NDDs. Microstructural abnormalities in the splenium of the CC were possibly shared among ASD and ADHD.