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BACKGROUND: The trajectory of attention-deficit hyperactivity disorder (ADHD) symptoms in children and adolescents, encompassing descending, stable, and ascending patterns, delineates their ADHD status as remission, persistence or late onset. However, the neural and genetic underpinnings governing the trajectory of ADHD remain inadequately elucidated. METHODS: In this study, we employed neuroimaging techniques, behavioral assessments, and genetic analyses on a cohort of 487 children aged 6-15 from the Children School Functions and Brain Development project at baseline and two follow-up tests for 1 year each (interval 1: 1.14 ± 0.32 years; interval 2: 1.14 ± 0.30 years). We applied a Latent class mixed model (LCMM) to identify the developmental trajectory of ADHD symptoms in children and adolescents, while investigating the neural correlates through gray matter volume (GMV) analysis and exploring the genetic underpinnings using polygenic risk scores (PRS). RESULTS: This study identified three distinct trajectories (ascending-high, stable-low, and descending-medium) of ADHD symptoms from childhood through adolescence. Utilizing the linear mixed-effects (LME) model, we discovered that attention hub regions served as the neural basis for these three developmental trajectories. These regions encompassed the left anterior cingulate cortex/medial prefrontal cortex (ACC/mPFC), responsible for inhibitory control; the right inferior parietal lobule (IPL), which facilitated conscious focus on exogenous stimuli; and the bilateral middle frontal gyrus/precentral gyrus (MFG/PCG), accountable for regulating both dorsal and ventral attention networks while playing a crucial role in flexible modulation of endogenous and extrinsic attention. Furthermore, our findings revealed that individuals in the ascending-high group exhibited the highest PRS for ADHD, followed by those in the descending-medium group, with individuals in the stable-low group displaying the lowest PRS. Notably, both ascending-high and descending-medium groups had significantly higher PRS compared to the stable-low group. CONCLUSIONS: The developmental trajectory of ADHD symptoms in the general population throughout childhood and adolescence can be reliably classified into ascending-high, stable-low, and descending-medium groups. The bilateral MFG/PCG, left ACC/mPFC, and right IPL may serve as crucial brain regions involved in attention processing, potentially determining these trajectories. Furthermore, the ascending-high pattern of ADHD symptoms exhibited the highest PRS for ADHD.
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Transtorno do Deficit de Atenção com Hiperatividade , Humanos , Transtorno do Deficit de Atenção com Hiperatividade/genética , Transtorno do Deficit de Atenção com Hiperatividade/fisiopatologia , Criança , Adolescente , Masculino , Feminino , Imageamento por Ressonância Magnética , Encéfalo/diagnóstico por imagem , Encéfalo/crescimento & desenvolvimento , Substância Cinzenta/diagnóstico por imagem , Substância Cinzenta/patologia , Neuroimagem , Estudos de CoortesRESUMO
NAD-dependent deacetylase Sirt2 is involved in mammalian metabolic activities, matching energy demand with energy production and expenditure, and is relevant to a variety of metabolic diseases. Here, we constructed Sirt2 knockout and adeno-associated virus overexpression mice and found that deletion of hepatic Sirt2 accelerated primary obesity and insulin resistance in mice with concomitant hepatic metabolic dysfunction. However, the key targets of Sirt2 are unknown. We identified the M2 isoform of pyruvate kinase (PKM2) as a key Sirt2 target involved in glycolysis in metabolic stress. Through yeast two-hybrid and mass spectrometry combined with multi-omics analysis, we identified candidate acetylation modification targets of Sirt2 on PKM2 lysine 135 (K135). The Sirt2-mediated deacetylation-ubiquitination switch of PKM2 regulated the development of glycolysis. Here, we found that Sirt2 deficiency led to impaired glucose tolerance and insulin resistance and induced primary obesity. Sirt2 severely disrupted liver function in mice under metabolic stress, exacerbated the metabolic burden on the liver, and affected glucose metabolism. Sirt2 underwent acetylation modification of lysine 135 of PKM2 through a histidine 187 enzyme active site-dependent effect and reduced ubiquitination of the K48 ubiquitin chain of PKM2. Our findings reveal that the hepatic glucose metabolism links nutrient state to whole-body energetics through the rhythmic regulation of Sirt2.
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Fígado , Piruvato Quinase , Sirtuína 2 , Estresse Fisiológico , Ubiquitinação , Animais , Humanos , Masculino , Camundongos , Acetilação , Glucose/metabolismo , Glicólise , Resistência à Insulina , Fígado/metabolismo , Camundongos Endogâmicos C57BL , Camundongos Knockout , Obesidade/metabolismo , Piruvato Quinase/metabolismo , Sirtuína 2/metabolismoRESUMO
Attention and reading are essential skills for successful schooling and in adult life. While previous studies have documented that attention development supports reading acquisition, whether and how learning to read may improve attention among school-age children and the brain structural and functional development that may be involved remain unknown. In this prospective longitudinal study, we examined bidirectional and longitudinal predictions between attention and reading development and the neural mediators of attention and reading development among school-age children using cross-lagged panel modeling. The results showed that better baseline reading performance significantly predicted better attention performance one year later after controlling for baseline attention performance. In contrast, after controlling for baseline reading performance, attention did not significantly predict reading performance one year later, while more attention problems also significantly predicted worse reading performance. Both the increasing gray matter volume of the left middle frontal gyrus and the increasing connectivity between the left middle frontal gyrus and the ventral attention network mediated the above significant longitudinal predictions. This study, directly revealed that reading skills may predict the development of important cognitive functions, such as attention, in school-age children. Therefore, learning to read is not only a challenge for school-age children but is also an important way to optimize attention and brain development.
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Encéfalo , Leitura , Criança , Adulto , Humanos , Estudos Longitudinais , Estudos Prospectivos , Lobo Frontal , Imageamento por Ressonância MagnéticaRESUMO
Human functional brain networks are dynamically organized to enable cognitive and behavioral flexibility to meet ever-changing environmental demands. Frontal-parietal network (FPN) and default mode network (DMN) are recognized to play an essential role in executive functions such as working memory. However, little is known about the developmental differences in the brain-state dynamics of these two networks involved in working memory from childhood to adulthood. Here, we implemented Bayesian switching dynamical systems approach to identify brain states of the FPN and DMN during working memory in 69 school-age children and 51 adults. We identified five brain states with rapid transitions, which are characterized by dynamic configurations among FPN and DMN nodes with active and inactive engagement in different task demands. Compared with adults, children exhibited less frequent brain states with the highest activity in FPN nodes dominant to high demand, and its occupancy rate increased with age. Children preferred to attain inactive brain states with low activity in both FPN and DMN nodes. Moreover, children exhibited lower transition probability from low-to-high demand states and such a transition was positively correlated with working memory performance. Notably, higher transition probability from low-to-high demand states was associated with a stronger structural connectivity across FPN and DMN, but with weaker structure-function coupling of these two networks. These findings extend our understanding of how FPN and DMN nodes are dynamically organized into a set of transient brain states to support moment-to-moment information updating during working memory and suggest immature organization of these functional brain networks in childhood, which is constrained by the structural connectivity.
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Mapeamento Encefálico , Memória de Curto Prazo , Adulto , Criança , Humanos , Adolescente , Adulto Jovem , Teorema de Bayes , Imageamento por Ressonância Magnética , Encéfalo/diagnóstico por imagem , Vias Neurais/diagnóstico por imagemRESUMO
The default mode network (DMN) is a workspace for convergence of internal and external information. The frontal parietal network (FPN) is indispensable to executive functioning. Yet, how they interplay to support cognitive development remains elusive. Using longitudinal developmental fMRI with an n-back paradigm, we show a heterogeneity of maturational changes in multivoxel activity and network connectivity among DMN and FPN nodes in 528 children and 103 young adults. Compared with adults, children exhibited prominent longitudinal improvement but still inferior behavioral performance, which paired with less pronounced DMN deactivation and weaker FPN activation in children, but stronger DMN coupling with FPN regions. Children's DMN reached an adult-like level earlier than FPN at both multivoxel activity pattern and intranetwork connectivity levels. Intrinsic DMN-FPN internetwork coupling in children mediated the relationship between age and working memory-related functional coupling of these networks, with posterior cingulate cortex (PCC)-dorsolateral prefrontal cortex (DLPFC) coupling emerging as most prominent pathway. Coupling of PCC-DLPFC may further work together with task-invoked activity in PCC to account for longitudinal improvement in behavioral performance in children. Our findings suggest that the DMN provides a scaffolding effect in support of an immature FPN that is critical for the development of executive functions in children.
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Cognição , Rede de Modo Padrão , Adulto Jovem , Criança , Humanos , Função Executiva/fisiologia , Memória de Curto Prazo/fisiologia , Lobo Frontal , Imageamento por Ressonância Magnética , Mapeamento Encefálico , Encéfalo/fisiologia , Rede Nervosa/fisiologiaRESUMO
BACKGROUND: Long non-coding RNAs (lncRNAs) are involved in many key bioprocesses, including the occurrence and development of rheumatoid arthritis (RA). We aimed to analyze the association of genetic variants of long non-coding RNA LOC553103 and its peripheral blood mononuclear cells (PBMC) expression with RA. METHODS: We enrolled 457 RA patients and 551 healthy controls and conducted a case-control study to analyze the relationship between LOC553103 gene rs272879 and the susceptibility of RA by TaqMan single nucleotide polymorphism genotyping. Among them, we sampled 92 cases and 92 controls, respectively, to detect the PBMC level of LOC553103 using quantitative real-time polymerase chain reaction technology. We explored the association between LOC553103 rs272879 and its PBMC expression levels in 71 RA patients. Mann-Whitney, Chi-square, and Spearman correlation analysis were used for statistical analysis and P-value <.05 was considered statistically significant. RESULTS: The genotype frequency of LOC553103 rs272879 CC was increased, and CG was decreased in RA patients compared to the control group (χ2 = 6.772, P = .034). The LOC553103 expression level in PBMC of RA patients was downregulated compared to healthy control (Z = -4.497, P < .001). Moreover, negative correlations were observed between the PBMC level of LOC553103 and erythrocyte sedimentation rate (rs = -0.262, P = .018), white blood cell count (rs = -0.382, P = .004), platelet (rs = -0.293, P = .030), and disease activity score in 28 joints (rs = -0.271, P = .016) in RA patients. CONCLUSIONS: This study provides the first evidence supporting an association between LOC553103 gene polymorphisms and susceptibility of RA and a relationship of PBMC level of LOC553103 with clinical manifestations and laboratory indicators of RA patients.
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Policy Points Employment is a key social determinant of health and well-being for the estimated 5.4 million autistic adults in the United States-just as it is for citizens without disabilities. Evaluation and monitoring of publicly funded employment services is paramount given the dramatic increases in adults with autism who need job supports. Vocational Rehabilitation agencies appeared to be absorbing short-term employment needs of autistic people, but Medicaid was severely lacking-and losing ground-in serving those who need longer-term employment services. Across both Vocational Rehabilitation and Medicaid, we estimated that only 1.1% of working-age autistic adults who potentially need employment services are actually receiving them-leaving an estimated 1.98 million autistic individuals without the employment services that are associated with achievement of well-being. CONTEXT: Employment is a key social determinant of health. As such, high rates of unemployment, underemployment, and poverty across the rapidly growing autistic population are concerning. A web of publicly funded services exists to support the employment, and associated health and well-being, of United States citizens with autism and other intellectual and developmental disabilities, namely through Vocational Rehabilitation (VR) and Medicaid home- and community-based services (HCBS) waivers. Given an absence of overarching surveillance of employment services, this study aimed to characterize the distribution of autistic service users across Medicaid versus VR, understand the types of employment services utilized within these programs and expenditures, and assess overall capacity to provide employment services as needs continue to increase. METHODS: This study examined the distribution of employment services among autistic people compared with those with intellectual disability using 2008-2016 data from the Centers for Medicare & Medicaid Services and the Rehabilitation Services Administration. Estimated need for employment services among autistic individuals was compared with capacity derived from VR service counts and a review of HCBS waivers. FINDINGS: The number of autistic people served through VR tripled during the study years, whereas those served through Medicaid only increased slightly. VR spending increased by 384% over the study years, whereas Medicaid costs decreased by 29%. Across VR and Medicaid, we estimated that only 1.1% of working-age autistic adults who needed employment services received them. CONCLUSIONS: Although VR appeared to be absorbing short-term employment needs of autistic individuals, Medicaid was severely lacking-and losing ground-in serving those who needed longer-term employment services. VR far outpaced Medicaid in both the number of autistic people served and total expenditures across the study years. However, an estimated 1.98 million autistic adults did not receive employment services that could be critical to improving their health and well-being.
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Transtorno Autístico , Pessoas com Deficiência , Adulto , Humanos , Idoso , Estados Unidos , Transtorno Autístico/reabilitação , Medicare , Emprego , Gastos em Saúde , MedicaidRESUMO
Sex differences in human emotion and related decision-making behaviors are recognized, which can be traced back early in development. However, our understanding of their underlying neurodevelopmental mechanisms remains elusive. Using developmental functional magnetic resonance imaging and computational approach, we investigated developmental sex differences in latent decision-making dynamics during negative emotion processing and related neurocognitive pathways in 243 school-aged children and 78 young adults. Behaviorally, girls exhibit higher response caution and more effective evidence accumulation, whereas boys show more impulsive response to negative facial expression stimuli. These effects parallel sex differences in emotion-related brain maturity linking to evidence accumulation, along with age-related decrease in emotional response in the basolateral amygdala and medial prefrontal cortex (MPFC) in girls and an increase in the centromedial amygdala (CMA) in boys. Moreover, girls exhibit age-related decreases in BLA-MPFC coupling linked to evidence accumulation, but boys exhibit increases in CMA-insula coupling associated with response caution. Our findings highlight the neurocomputational accounts for developmental sex differences in emotion and emotion-related behaviors and provide important implications into the neurodevelopmental mechanisms of sex differences in latent emotional decision-making dynamics. This informs the emergence of sex differences in typical and atypical neurodevelopment of children's emotion and related functions.
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Tonsila do Cerebelo , Caracteres Sexuais , Tonsila do Cerebelo/diagnóstico por imagem , Tonsila do Cerebelo/fisiologia , Criança , Emoções/fisiologia , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Vias Neurais/diagnóstico por imagem , Vias Neurais/fisiologia , Córtex Pré-Frontal/diagnóstico por imagem , Córtex Pré-Frontal/fisiologia , Adulto JovemRESUMO
Functional brain networks require dynamic reconfiguration to support flexible cognitive function. However, the developmental principles shaping brain network dynamics remain poorly understood. Here, we report the longitudinal development of large-scale brain network dynamics during childhood and adolescence, and its connection with gene expression profiles. Using a multilayer network model, we show the temporally varying modular architecture of child brain networks, with higher network switching primarily in the association cortex and lower switching in the primary regions. This topographical profile exhibits progressive maturation, which manifests as reduced modular dynamics, particularly in the transmodal (e.g., default-mode and frontoparietal) and sensorimotor regions. These developmental refinements mediate age-related enhancements of global network segregation and are linked with the expression profiles of genes associated with the enrichment of ion transport and nucleobase-containing compound transport. These results highlight a progressive stabilization of brain dynamics, which expand our understanding of the neural mechanisms that underlie cognitive development.
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Encéfalo , Imageamento por Ressonância Magnética , Adolescente , Mapeamento Encefálico , Córtex Cerebral , Criança , Cognição , Humanos , Imageamento por Ressonância Magnética/métodos , Vias NeuraisRESUMO
Recent studies have suggested that-beyond automaticity and prosody-reading fluency involves parallel processing of adjacent items presented in a sequence, termed "cascaded processing." To date, most studies examining cascaded processing have been conducted in alphabetic orthographies. Thus, the purpose of this study was to examine the cascaded processing hypothesis in Chinese. A total of 119 Grade 1 Chinese children (61 boys and 58 girls; Mage = 7.30 years, SD = 0.31) were assessed on serial and discrete naming of digits as well as on serial and discrete naming of high-frequency one- and two-character words and low-frequency one-character words presented with pinyin. Results of hierarchical regression analyses showed, first, that serial digit naming was a unique predictor of discrete naming of low-frequency one-character words and two-character words, but not of high-frequency one-character words. Second, serial digit naming was a unique predictor of reading of high-frequency one- and two-character word reading after controlling for discrete word reading. These findings suggest that Chinese first graders process high-frequency characters holistically (similar to simple digits), which then facilitates parallel processing of multiple stimuli when they are presented in a sequence.
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População do Leste Asiático , Leitura , Criança , Feminino , Humanos , Masculino , Reconhecimento Visual de ModelosRESUMO
Sensation seeking has been extensively demonstrated as a risk factor for substance use. Potential bidirectional associations between sensation seeking and substance use at the within-person level are incompletely understood. The present study examined longitudinal trajectories of sensation seeking and substance use and bidirectional longitudinal associations between sensation seeking and substance use in Chinese adolescents during a 3-year period over three time points. A total of 10,138 adolescents (59.8%) male; Mage = 16.77, SD = 0.83 at time (1) were surveyed. Sensation seeking and substance use frequency increased concomitantly over time. At the within-person level, sensation seeking and substance use were reciprocally predictable, and there were no evidence of sex difference in longitudinal associations. This study provides unique data concerning the relationship between sensation seeking and substance use in a sample of Chinese adolescents, and highlights the importance of identifying sensation seeking behaviors to prevent substance use.
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Comportamento do Adolescente , Transtornos Relacionados ao Uso de Substâncias , Humanos , Masculino , Adolescente , Feminino , Estudos Prospectivos , População do Leste Asiático , Assunção de Riscos , Transtornos Relacionados ao Uso de Substâncias/epidemiologia , SensaçãoRESUMO
BACKGROUND: Sclerostin, a regulator of bone metabolism and vascular calcification involved in regulating the Wnt/ß-catenin signaling pathway, has been shown to be involved in the pathogenesis of rheumatoid arthritis (RA). However, current results regarding the circulating sclerostin level of RA patients are debatable. This study aimed to evaluate the circulating level of sclerostin in RA patients and briefly summarize its role. METHOD: PubMed, EMBASE, and the Cochrane Library databases were systematically searched till May 27, 2021, for eligible articles. Useful data from all qualified papers were systematically extracted and analyzed using Stata 12.0 software (Stata Corp LP, College Station, TX, USA). RESULTS: Overall, 13 qualifying studies including 1030 cases and 561 normal controls were analyzed in this updated meta-analysis. Forest plot of this meta-analysis showed that RA patients had higher circulating sclerostin levels (Pâ¯< 0.001, standardized mean difference [SMD]â¯= 0.916, 95% CI: 0.235-1.597) compared to normal controls. Subgroup analyses implied that age, region, and assay method were associated with sclerostin level in RA patients. CONCLUSION: RA patients have higher circulating sclerostin levels, and these was influenced by age, region, and assay method.
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Artrite Reumatoide , Humanos , Artrite Reumatoide/diagnóstico , Artrite Reumatoide/patologia , Proteínas Adaptadoras de Transdução de SinalRESUMO
Native language background exerts constraints on the individual's brain automatic response while learning a second language. It remains unclear, however, whether second language immersion experience could help the brain overcome such constraints and meet the requirements of a second language. This study compared native Chinese speakers with English-as-a-second-language immersion experience (immersive English learners), native Chinese speakers without English-as-a-second-language immersion experience (nonimmersive English learners), and native English speakers with an ERP cross-modal MMN paradigm. The results found that English-as-a-second-language immersion could benefit speech perception for native Chinese speakers. In addition, both immersive English learners and native English speakers showed enhanced cross-modal MMN, indicating that second language immersion could help native Chinese speakers successfully integrate English letter-sound like native English speakers. The present study further revealed that English listening and speaking exposure in an immersive environment is important in English letter-sound integration for immersive English learners.
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Multilinguismo , Percepção da Fala , Humanos , Idioma , Leitura , Imersão , Percepção da Fala/fisiologia , Encéfalo/fisiologia , ChinaRESUMO
Dickkopf-1 (DKK-1) is mostly known as a mature inhibitor of classic Wnt signaling pathways, which plays a critically role in regulating bone formation and bone metastasis. In recent years, the roles of DKK-1 played in bone resorption, bone formation, immune homeostasis and inflammation have been investigated. The role of DKK-1 in the pathogenesis and treatment of autoimmune diseases (ADs), including rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), etc, has attracted widespread attention. Various studies have found that DKK-1 may be used as a biomarker for the occurrence and development of ADs, and as a potential target for the treatment of ADs. In this review, we have briefly summed up the intricate immunological functions and regulatory mechanisms of DKK-1 in ADs, aiming to further learning more about the role of DKK-1 involved in the pathogenesis of ADs and provide an outlook for the potential future researches.
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Artrite Reumatoide , Doenças Autoimunes , Reabsorção Óssea , Lúpus Eritematoso Sistêmico , Humanos , Peptídeos e Proteínas de Sinalização Intercelular , Doenças Autoimunes/tratamento farmacológico , Artrite Reumatoide/tratamento farmacológico , Lúpus Eritematoso Sistêmico/tratamento farmacológicoRESUMO
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can cause coronavirus disease 2019 (COVID-19), an acute respiratory inflammation that has emerged worldwide since December 2019, and it quickly became a global epidemic. Inflammatory bowel disease (IBD) is a group of chronic nonspecific intestinal inflammatory diseases whose etiology has not been elucidated. The two have many overlapping symptoms in clinical presentation, such as abdominal pain, diarrhea, pneumonia, etc. Imbalance of the autoimmune system in IBD patients and long-term use of immunosuppressive drugs may increase the risk of infection; and systemic symptoms caused by COVID-19 may also induce or exacerbate intestinal inflammation. It has been found that the SARS-CoV-2 receptor angiotensin converting enzyme 2, which is highly expressed in the lung and intestine, is an inflammatory protective factor, and is downregulated and upregulated in COVID-19 and IBD, respectively, suggesting that there may be a coregulatory pathway. In addition, the immune activation pattern of COVID-19 and the cytokine storm in the inflammatory response have similar roles in IBD, indicating that the two diseases may influence each other. Therefore, this review aimed to address the following research questions: whether SARS-CoV-2 infection leads to the progression of IBD; whether IBD increases the risk of COVID-19 infection and poor prognosis; possible common mechanisms and genetic cross-linking between the two diseases; new treatment and care strategies for IBD patients, and the feasibility and risk of vaccination in the context of the COVID-19 epidemic.
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COVID-19 , Doenças Inflamatórias Intestinais , Enzima de Conversão de Angiotensina 2 , COVID-19/complicações , Síndrome da Liberação de Citocina , Humanos , Doenças Inflamatórias Intestinais/complicações , Peptidil Dipeptidase A/genética , SARS-CoV-2RESUMO
In adults, music and speech share many neurocognitive functions, but how do they interact in a developing brain? We compared the effects of music and foreign language training on auditory neurocognition in Chinese children aged 8-11 years. We delivered group-based training programs in music and foreign language using a randomized controlled trial. A passive control group was also included. Before and after these year-long extracurricular programs, auditory event-related potentials were recorded (n = 123 and 85 before and after the program, respectively). Through these recordings, we probed early auditory predictive brain processes. To our surprise, the language program facilitated the children's early auditory predictive brain processes significantly more than did the music program. This facilitation was most evident in pitch encoding when the experimental paradigm was musically relevant. When these processes were probed by a paradigm more focused on basic sound features, we found early predictive pitch encoding to be facilitated by music training. Thus, a foreign language program is able to foster auditory and music neurocognition, at least in tonal language speakers, in a manner comparable to that by a music program. Our results support the tight coupling of musical and linguistic brain functions also in the developing brain.
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Música , Adulto , Criança , Humanos , Idioma , Terapia da Linguagem , Música/psicologia , Percepção da Altura Sonora , FalaRESUMO
The objective of this experiment was to examine the effect of milk replacer (MR) feeding rate (FR) and frequency (FF) on glucose metabolism before and after weaning during summer and winter in the subtropical climate of the southeastern United States. Holstein calves (n = 48/season) were enrolled at 8 d of age (DOA) in the summer (June to August, body weight = 40.6 ± 0.7 kg) and winter (November to January, body weight = 41.9 ± 0.8 kg). In each season, calves were randomly assigned to 1 of 4 treatments in a 2 × 2 factorial arrangement including 2 FR [0.65 (low) or 0.76 kg of solids/d (high) of a 26% CP and 17% fat MR] and 2 FF [2× (0700 and 1600 h) or 3× (0700, 1600, and 2200 h)]. Calves were managed similarly and housed in polyethylene hutches bedded with sand. Milk replacer (12.5%) was fed based on treatments until 42 DOA when FR was reduced by half and offered 1×/d (0700 h) for 7 d. Plasma was collected weekly at 1400 h for analyses of glucose and insulin concentrations in all calves. Pre- and postprandial glucose and insulin concentrations of a subset of calves (n = 10/treatment per season) were measured on 20 DOA. A subset of calves (n = 8/treatment per season) was subjected to an intravenous glucose tolerance test (GTT) on 27 and 57 DOA and insulin challenge on 28 and 58 DOA at 1030 h. Average ambient temperature was 26.1 ± 2.2°C in summer and 12.9 ± 5.4°C in winter. During the preweaning period in both seasons, feeding high increased plasma glucose concentrations compared with low, and increasing FF reduced basal insulin concentrations. Compared with 2×, feeding 3× did not affect postprandial glucose but lowered insulin in the summer, whereas in the winter, increased glucose from 30 to 180 min but lowered insulin from 240 to 420 min after MR feeding. Following GTT before weaning in both seasons, 3× reduced insulin increment and area under the curve compared with 2× without affecting glucose disposal. After weaning, treatment did not affect glucose disposal or insulin responses after GTT during winter, but calves fed 3× had faster glucose disposal and stronger insulin responses than 2× during summer. In both summer and winter, preweaned calves fed 3× had greater decrement and area under the curve of plasma glucose after insulin challenge, suggesting enhanced peripheral tissue insulin response compared with 2×. This effect persisted after weaning only during summer. Increasing FR had no effect on metabolic responses in both seasons. In conclusion, increasing MR FF from 2 to 3 times per day reduced insulin secretion but enhanced insulin response on peripheral tissues of preweaned calves regardless of season.
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Substitutos do Leite , Leite , Ração Animal/análise , Animais , Peso Corporal , Bovinos , Dieta/veterinária , Glucose , DesmameRESUMO
To evaluate the effects of milk replacer (MR) feeding rate (FR) and frequency (FF) on performance, abomasal emptying, and nutrient digestibility in the southeastern United States, Holstein calves (n = 48/season) were enrolled at 8 d of age (DOA) during summer [June to August, body weight (BW; mean ± SD) = 40.71 ± 4.35 kg] and winter (November to January, BW = 42.03 ± 3.83 kg). Within season, calves were randomly assigned to 1 of 4 treatments in a 2 × 2 factorial arrangement including 2 FR [0.65 (low) or 0.76 kg of solid per day (high) of a 26% crude protein and 17% fat MR], and 2 FF [2× (0700 and 1600 h) or 3× (0700, 1600, and 2200 h) daily]. Calves were housed in polyethylene hutches and managed similarly throughout the trial. Milk replacer (12.5% solids) was fed to calves based on their respective treatments until 42 DOA, when MR allowance was reduced by 50% and offered once a day (0700 h) for the following 7 d until weaning. Calves remained on trial until 63 DOA. Calf starter and water were offered ad libitum. Ambient temperature and relative humidity inside and outside hutches were measured hourly. Starter and MR intakes were recorded daily. Respiration rate and rectal temperature were recorded 3 times a week. Structural growth and BW were measured weekly. Acetaminophen (50 mg/kg of BW) mixed with MR was fed to a subset of calves (0700 h, n = 10/treatment per season) on 20 DOA. Plasma was collected at 15, 30, 60, 90, 120, 150, 180, 210, 240, 270, 300, 330, 360, 420, and 480 min after feeding, to analyze acetaminophen. The acetaminophen concentration-time curve was modeled to the first derivative of Siegel's modified power exponential equation, and the time for plasma acetaminophen to reach maximum (Tmax) was calculated to evaluate abomasal emptying rate. During the pre- (14.9-17.9 DOA) and postweaning (51.0-54.0 DOA) periods, a subset (n = 8/treatment per season) of calves was used to determine the apparent digestibility of nutrients, using chromic oxide as the external marker. Feeding 3× reduced preweaning respiration rate during summer and reduced rectal temperature during winter. Increasing FR improved BW gain and structural growth. Feeding more times per day tended to improve growth during winter but not summer. We found no effect of treatment on nutrient digestibility. Increasing FR had no effect on Tmax during winter but tended to delay Tmax of plasma acetaminophen during summer. Regardless of season, increasing FF lowered Tmax of plasma acetaminophen. In conclusion, increasing FF accelerated abomasal emptying and might reduce heat load of preweaning dairy calves but improved growth only during winter. Increased MR allowance improved growth in both seasons but delayed abomasal emptying only under heat stress conditions.
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Substitutos do Leite , Leite , Ração Animal/análise , Animais , Peso Corporal , Bovinos , Dieta/veterinária , Nutrientes , DesmameRESUMO
IMPORTANCE: Rates of occupational therapy service utilization among people with autism spectrum disorder (ASD) or intellectual disability (ID) have not been explored in population-based samples. OBJECTIVE: To describe occupational therapy services delivered to Medicaid-eligible persons younger than age 65 yr identified as having ASD, ID, or both and to evaluate demographic factors associated with occupational therapy service utilization in this population. DESIGN: Retrospective, case-control, cohort study using claims records from Medicaid Analytic eXtract files (2009-2012). SETTING: Data from all 50 states and Washington, DC. PARTICIPANTS: Beneficiaries identified as having ASD only, ASD+ID, or ID only who were younger than age 18 yr (N = 664,214) and ages 18-64 yr (N = 702,338). Outcomes and Measures: We analyzed Current Procedural Terminology® and Healthcare Common Procedure Coding System procedure codes, Medicaid Statistical Information System type of service codes, and Center for Medicare & Medicaid Services provider specialty codes. RESULTS: Only 3.7% to 6.3% of eligible adult beneficiaries received occupational therapy; in contrast, 20.5% to 24.2% of children received occupational therapy. Significant predictors of service use varied by group; however, differences by race-ethnicity, eligibility on the basis of poverty, and geographic location were observed. Among children, the most frequent billing code was for "therapeutic activities" (43%-60%); among adults, it was "community/work reintegration training" (29%-39%). CONCLUSIONS AND RELEVANCE: Billed procedure code patterns do not consistently reflect the unique occupational focus that occupational therapy providers deliver to people with developmental disabilities. Disparities in occupational therapy receipt warrant further attention to understand the social and structural factors affecting service delivery. What This Article Adds: Occupational therapy services paid for by Medicaid are used more frequently by children with ASD and ID than by adults with these diagnoses. Greater understanding of the intersectional factors that drive service delivery and disparities is needed.
Assuntos
Transtorno do Espectro Autista , Transtorno Autístico , Deficiência Intelectual , Terapia Ocupacional , Adolescente , Adulto , Idoso , Criança , Estudos de Coortes , Humanos , Medicaid , Medicare , Pessoa de Meia-Idade , Estudos Retrospectivos , Estados Unidos , Adulto JovemRESUMO
The default-mode network (DMN) is a set of functionally connected regions that play crucial roles in internal cognitive processing. Previous resting-state fMRI studies have demonstrated that the intrinsic functional organization of the DMN undergoes remarkable reconfigurations during childhood and adolescence. However, these studies have mainly focused on cross-sectional designs with small sample sizes, limiting the consistency and interpretations of the findings. Here, we used a large sample of longitudinal resting-state fMRI data comprising 305 typically developing children (6-12 years of age at baseline, 491 scans in total) and graph theoretical approaches to delineate the developmental trajectories of the functional architecture of the DMN. For each child, the DMN was constructed according to a prior parcellation with 32 brain nodes. We showed that the overall connectivity increased in strength from childhood to adolescence and became spatially similar to that in the young adult group (N = 61, 18-28 years of age). These increases were primarily located in the midline structures. Global and local network efficiency in the DMN also increased with age, indicating an enhanced capability in parallel information communication within the brain system. Based on the divergent developmental rates of nodal centrality, we identified three subclusters within the DMN, with the fastest rates in the cluster mainly comprising the anterior medial prefrontal cortex and posterior cingulate cortex. Together, our findings highlight the developmental patterns of the functional architecture in the DMN from childhood to adolescence, which has implications for the understanding of network mechanisms underlying the cognitive development of individuals.