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1.
J Adolesc Health ; 2024 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-38506779

RESUMO

PURPOSE: Youth suicide has been increasing and became a public health concern worldwide. Identifying insufficient sleep as the potential risk factor is critical to reducing suicide risk and increasing trends. This study aimed to determine whether insufficient sleep is associated with increasing trends in suicidal behaviors and disparities by sex, age, and race/ethnicity among school adolescents. METHODS: The present study used biennial data from the US nationally representative Youth Risk Behavior Survey from 2007 to 2019. Joinpoint regression models were used to estimate biennial percent changes (BPCs) and average BPCs (ABPCs) of suicidal behaviors by sleep duration. Logistic regression models were used to examine the association between insufficient sleep and suicidal behaviors. RESULTS: Of 73,356 adolescent students included (mean [standard deviation] age, 16.11 [1.23] years), 50.03% were female. Suicidal ideation and suicide plan among insufficient sleep group increased from 2007 to 2019 (BPC = 2.88% [95% confidence interval {CI}: 1.65%, 4.13%]; BPC = 3.42% [95% CI: 2.09%, 4.77%]), but were nonsignificant among sufficient sleep group. Trends in suicidal ideation (ABPC = 3.03% [95% CI: 1.35%, 4.73%]) and suicide plan (ABPC = 4.03% [95% CI: 2.47%, 5.62%]) among female adolescents with insufficient sleep increased, but nonsignificant among male adolescents with insufficient sleep. Suicidal ideation (ABPC = 1.73% [95% CI: 0.51%, 2.97%]) and suicide plan (ABPC = 2.31% [95% CI: 0.70%, 3.95%]) increased among younger adolescents only with insufficient sleep, whereas suicide trends by sleep duration were similar among older adolescents. Suicide plan among insufficient sleep group increased across the four racial groups, with BPC highest for the White (BPC = 3.48% [95% CI: 1.31%, 5.69%]), and lowest for the Hispanic/Latino (BPC = 1.18% [95% CI: 0.15%, 2.23%]), but were nonsignificant among sufficient sleep group except for the White (BPC = 2.83% [95% CI: 0.62%, 5.09%]). DISCUSSION: Insufficient sleep was disproportionately associated with increasing trends in suicidal behaviors among female, younger, and non-White adolescent students. Ensuring sufficient sleep can potentially reduce suicide among school adolescents.

2.
J Clin Sleep Med ; 2024 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-38372158

RESUMO

STUDY OBJECTIVES: The reduction in daytime sleep during early life is considered one of the indicators of the maturation of sleep patterns, which is closely associated with cognitive development. The current study aims to analyze the relationships between daytime sleep duration (DSD) during infancy and cognitive development at 6 and 10 years. METHODS: The study included 262 mothers with their newborns from the Shanghai Sleep Birth Cohort Study, spanning eleven follow-ups from 42 days to 10 years. Sleep parameters were assessed using parent-report questionnaires at each follow-up, and cognitive development was evaluated with the Wechsler Intelligence Scale for Children, 4th edition at 6 and 10 years. RESULTS: Two distinct DSD trajectories in early childhood were identified: "typical DSD" (66.7%) and "infancy excessive DSD" (33.3%). Children in the "infancy excessive DSD" trajectory exhibited lower working memory scores than those in the "typical DSD" trajectory at 6 years (Mean difference=5.90, 95% CI [1.83, 9.96], p=0.005) and 10 years (Mean difference=4.37, 95% CI [0.26, 8.48], p=0.037). Additional analysis in a relatively homogeneous sample consistently showed correlations between DSD trajectories and working memory performance. No consistent significant differences were found in other domains of cognitive development. CONCLUSIONS: Excessive daytime sleep during infancy may serve as an early indicator for poor working memory at school age. These findings raise concerns about the long-term cognitive development of infants with excessive DSD.

3.
ACS Pharmacol Transl Sci ; 7(1): 212-221, 2024 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-38230295

RESUMO

Antibody-drug conjugates (ADCs), integrating high specificity of antigen-targeting antibodies and high potency of cell-killing chemical drugs, have become one of the most rapidly expanding therapeutic biologics in oncology. Although ADCs were widely studied from multiple aspects, overall structural elucidation with comprehensive understanding of variants is scarcely reported. Here, for the first time, we present a holistic and in-depth characterization of an interchain cysteine-conjugated ADC, focusing on conjugation and charge heterogeneity, and in vitro biological activities. Conjugation mapping utilized a bottom-up approach, unraveled positional isomer composition, provided insights into the conjugation process, and elucidated how conjugation affects the physicochemical and biological properties of an ADC. Charge profiling combined bottom-up and top-down approaches to interrogate the origin of charge heterogeneity, its impact on function, and best practice for characterization. Specifically, we pioneered the utilization of capillary isoelectric focusing-mass spectrometry to decode not only critical post-translational modifications but also drug load and positional isomer distribution. The study design provides general guidance for in-depth characterization of ADCs, and the analytical findings in turn benefit the discovery and development of future ADCs.

4.
JAMA Netw Open ; 6(12): e2347623, 2023 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-38095895

RESUMO

Importance: Sleep disturbances and mental health problems are highly comorbid and bidirectionally correlated across childhood. The association between the natural history of sleep disturbances and the transition of mental health problems has not been quantified. Objective: To examine the association between the natural history of sleep disturbances and resolved and incident emotional and behavioral difficulties (EBDs). Design, Setting, and Participants: This cohort study used data from the Shanghai Children's Health, Education and Lifestyle Evaluation-Preschool (SCHEDULE-P), a prospective and population-based longitudinal cohort study of children enrolled in preschools in Shanghai, China, from November 10 to 24, 2016. A total of 20 324 children aged 3 to 4 years were recruited from the junior class of 191 kindergartens, of whom 17 233 (84.8%) participated in the 2-year follow-up. A multilevel regression model was used to evaluate the association between the development of sleep disturbances and the occurrence of resolved and incident EBDs. The data analysis spanned from August 4, 2021, to October 31, 2023. Exposures: Sleep disturbances were assessed using the Children's Sleep Habit Questionnaire; EBDs were assessed using the Strengths and Difficulties Questionnaire. Main Outcomes and Measures: Occurrence of incident and resolved EBDs at the 2-year follow-up. Results: The cohort included 17 182 participants, with a mean (SD) age of 3.73 (0.29) years at enrollment; 52.0% were boys. The prevalence of EBDs at school entry and graduation years was 27.8% and 18.7%, respectively, while the prevalence of sleep disturbances was 41.3% and 31.5%, respectively. Among those with EBDs at the entry year, 35.0% maintained stability in the graduation year, while sleep disturbances were stable in 50.0% of those with sleep disturbances. After controlling for confounding factors, the odds ratio (OR) for resolved EBDs was lower in the incident sleep disturbance (ISD) group (OR, 0.50 [95% CI, 0.41-0.62]; P < .001) and stable sleep disturbance (SSD) group (OR, 0.47 [95% CI, 0.40-0.56]; P < .001) compared with the group with no sleep disturbances. The ORs for incident EBDs among the ISD group (OR, 2.58 [95% CI, 2.22-3.01]; P < .001) and SSD group (OR, 2.29, [95% CI, 1.98-2.64]; P < .001) were higher than among the group with no sleep disturbances. Conclusions and Relevance: In this prospective cohort study, the natural history of sleep disturbances among preschool-aged children was associated with both resolved and incident EBDs. Routine screening and precise intervention for sleep disturbances may benefit the psychosocial well-being of this population.


Assuntos
Transtornos do Sono-Vigília , Criança , Masculino , Humanos , Pré-Escolar , Feminino , Estudos de Coortes , Estudos Prospectivos , Estudos Longitudinais , China/epidemiologia , Transtornos do Sono-Vigília/epidemiologia , Transtornos do Sono-Vigília/psicologia , Sono
5.
Front Endocrinol (Lausanne) ; 14: 1259172, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38075047

RESUMO

Background: There is an increasing tendency toward early pubertal development, and sleep might be related to pubertal onset. We aimed to investigate the association of sleep duration and bedtime with early pubertal development. Methods: This was a cross-sectional study of 8,007 children (53.6% boys) from Qufu city, Shandong province and Zhongshan city, Guangdong province, China. Data on sleep duration and bedtime were obtained by questionnaire. Early pubertal development was the primary outcome and it was evaluated by the pediatrician according to Tanner staging. Logistic regression models were used to separately examine the association between sleep duration or bedtime and early pubertal development, controlling body mass index (BMI), dietary pattern, soft drink, feeding pattern and mother's BMI. Results: In boys, short sleep duration was strongly related to early pubertal development [OR (95%CI): 4.26 (1.30, 13.94)], and this association was intensified after adjusted BMI, dietary pattern, soft drink, feeding pattern and mother's BMI. In girls, OR (95%CI) was 1.62 (1.04, 2.51), and increased after controlling BMI. Bedtime was associated with early pubertal development on weekdays [OR (95%CI): 6.39 (1.54, 26.45) in boys and 1.93 (1.23, 3.05) in girls], but not on weekends [OR (95%CI): 2.49 (0.61, 10.21) in boys; 1.31 (0.76, 2.25) in girls]. Conclusion: This study underscores the positive association between the risk of early pubertal development and insufficient sleep duration and late bedtime.


Assuntos
Privação do Sono , Sono , Masculino , Criança , Feminino , Humanos , Estudos Transversais , Índice de Massa Corporal , China/epidemiologia
6.
J Affect Disord ; 324: 403-409, 2023 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-36586610

RESUMO

BACKGROUND: There is a large body of evidence suggesting that maternal prenatal depression significantly predicts mental health problems in children. However, little is known about the role of maternal childhood trauma within this effect. METHODS: The current study utilized a sample of 187 mother-child dyads (51.3 % boys) from the Shanghai Sleep Birth Cohort (SSBC), a six-year prospective longitudinal study. The effects of maternal depression at late pregnancy (Center for Epidemiological Survey-Depression Scale) on the child mental health at six years old (Strengths and Difficulties Questionnaire) were analyzed, with different types of maternal childhood trauma (Childhood Trauma Questionnaire) being examined as moderators. RESULTS: The results showed that maternal prenatal depression positively predicted child mental health problems (ß = 0.13, p < .05) and there was a significant moderating effect of maternal childhood emotional abuse (ß = -0.05, p < .05); that is, in mothers with high childhood emotional abuse, child mental health problems remained high regardless of maternal prenatal depression (ß = -0.02, p = .78), while in mothers with low childhood emotional abuse, maternal prenatal depression significantly predicted child behavioral and emotional problems (ß = 0.20, p < .05). LIMITATIONS: Relatively high socio-economic status samples, retrospective reports of maternal childhood trauma and the single reporter were the limitations of this study. CONCLUSIONS: The findings provided new insights into the impact of maternal prenatal depression on child mental health, highlighting the importance of intervention efforts targeting mothers with prenatal depression and childhood trauma history.


Assuntos
Experiências Adversas da Infância , Depressão , Feminino , Masculino , Criança , Humanos , Gravidez , Depressão/epidemiologia , Estudos Longitudinais , Estudos Prospectivos , Estudos Retrospectivos , Saúde Mental , Relações Mãe-Filho/psicologia , China/epidemiologia , Mães/psicologia
7.
Sleep ; 45(5)2022 05 12.
Artigo em Inglês | MEDLINE | ID: mdl-35554573

RESUMO

STUDY OBJECTIVES: To investigate trajectories of early childhood sleep in the first 3 years and their association with maternal depressive symptoms. METHODS: Data were from 243 Chinese mother-child dyads. Children's sleep duration and night-waking were assessed using the Brief Infant Sleep Questionnaire (BISQ) at 42 days, 3, 6, 9, 12, 18, 24, and 36 months postpartum. The Center for Epidemiological Survey-Depression Scale (CES-D), Edinburgh Postnatal Depression Scale (EPDS), and Profile of Mood States (POMS) were used to assess maternal depressive symptoms at late pregnancy, 42 days, and 36 months postpartum, respectively. Early childhood sleep trajectories were estimated with group-based trajectory models. The association between early childhood sleep trajectories and maternal depressive symptoms was examined with binary and multinomial logistic regression models and linear regression models. RESULTS: Three trajectories of daytime sleep duration ("short", 14.4%; "medium", 60.4%; "long", 25.2%), nighttime sleep duration ("increasing", 17.6%; "stable", 76.3%; "decreasing", 6.1%), and total sleep duration ("short", 21.5%; "medium", 59.9%; "long",18.6%), and two trajectories of night-waking ("resolving", 22.9%; "persistent", 77.1%) were identified. Controlling for confounding factors, maternal depression at 42 days postpartum was associated with higher risks for short daytime sleep duration and persistent night-waking in children. Persistent night-waking in children was associated with increased maternal depressive symptoms at 36 months postpartum. CONCLUSION: Early childhood sleep follows distinct trajectories in the first 3 years of life. The trajectories of short daytime sleep duration and persistent night-waking are associated with maternal depression. The findings indicate tailored interventions should target both unfavorable early childhood sleep trajectories and maternal depression.


Assuntos
Depressão Pós-Parto , Distúrbios do Início e da Manutenção do Sono , Pré-Escolar , Depressão/complicações , Depressão/epidemiologia , Depressão Pós-Parto/epidemiologia , Feminino , Humanos , Lactente , Mães , Gravidez , Estudos Prospectivos , Sono
8.
Clin Epigenetics ; 14(1): 66, 2022 05 20.
Artigo em Inglês | MEDLINE | ID: mdl-35596190

RESUMO

BACKGROUND: Childhood overweight/obesity is a global public health concern. It is important to identify its early-life risk factors. Maternal poor sleep is common in late pregnancy, and previous studies indicated that poor sleep may influence the offspring's adiposity status. However, very few studies in humans investigated the effect of the different sleep parameters (sleep quantity, quality, and timing) on the offspring's adiposity indicators, and long-term studies are even more scarce. In addition, the underlying mechanism remains unclear. The present study therefore aimed to examine the association between the three maternal sleep dimensions in the late pregnancy and the offspring adiposity indicators and to explore the potential mediating effect of the cord blood DNA methylation in the above association. METHODS: Included participants in the current study were 2211 healthy pregnant women with singleton gestation from the Shanghai Birth Cohort (SBC) and Shanghai Sleep Birth Cohort (SSBC). Maternal nighttime sleep duration, quality, and midpoint (an indicator of circadian rhythm) were assessed by the same instrument in both cohorts during late pregnancy, and the offspring's body mass index (BMI) and subcutaneous fat (SF) were measured at 2 years old. Additionally, in 231 SSBC samples, the genome-wide DNA methylation levels were measured using the Illumina Infinium Methylation EPIC BeadChip. The multivariate linear regression was used to determine the associations between the maternal sleep parameters and the offspring adiposity indicators. The epigenome-wide association study was conducted to identify the maternal sleep-related CpG sites. The mediation analysis was performed to evaluate the potential intermediate role of DNA methylation in the association between maternal sleep and offspring adiposity indicators. RESULTS: The mean maternal nighttime sleep duration and the sleep midpoint for combined cohorts were 9.24 ± 1.13 h and 3.02 ± 0.82, respectively, and 24.5% of pregnant women experienced poor sleep quality in late pregnancy. After adjusting for the covariates, the maternal later sleep midpoint was associated with the increased SF in offspring (Coef. = 0.62, 95% CI 0.37-0.87, p < 0.001) at 2 years old. However, no significant associations of the nighttime sleep duration or sleep quality with the offspring adiposity indicators were found. In the SSBC sample, 45 differential methylated probes (DMPs) were associated with the maternal sleep midpoint, and then, we observed 10 and 3 DMPs that were also associated with the offspring's SF and BMI at 2 years, of which cg04351668 (MARCH9) and cg12232388 significantly mediated the relationship of sleep midpoint and SF and cg12232388 and cg12225226 mediated the sleep midpoint-BMI association, respectively. CONCLUSIONS: Maternal later sleep timing in late pregnancy was associated with higher childhood adiposity in the offspring. Cord blood DNA methylation may play a mediation role in that relationship.


Assuntos
Adiposidade , Obesidade Infantil , Adiposidade/genética , Peso ao Nascer , Índice de Massa Corporal , Criança , Pré-Escolar , China , Metilação de DNA , Feminino , Humanos , Gravidez , Estudos Prospectivos , Sono/genética
9.
Child Adolesc Psychiatry Ment Health ; 16(1): 34, 2022 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-35534893

RESUMO

BACKGROUND: While recent works suggested that overweight/obesity may impair executive function (EF), the overweight/obesity-EF relationship has not been well studied in adolescents. Furthermore, no research has investigated adolescent EF impairments across the weight spectrum (e.g., underweight or thinness, normal, overweight/obesity), especially those with underweight condition, with the moderating effect of negative emotions in the weight-EF association being limitedly investigated. We aimed to determine whether overall and abdominal weight spectrum associated with EF impairments and to identity whether negative emotions moderate the weight-EF link in adolescents. METHODS: We applied a subsample of the SCHEDULE-A project. Adolescents (11-18 years) were recruited using a multi-stage cluster random sampling approach. We measured the overall and abdominal weight spectrum by body mass index z-score and waist-to-height ratio, respectively. We used the Behavior Rating Inventory of Executive Function (BRIEF) to evaluate adolescent EF in nature setting, and utilized the Depression Anxiety and Stress Scales (DASS-21) to assess three types of negative emotional status (i.e., depression, anxiety, and stress). RESULTS: Of the 1935 adolescents, 963 (49.8%) were male. We observed that abdominal, not overall, overweight was associated with the Global Executive Composite (GEC) impairment (OR = 1.59, 95% CI 1.07-2.35), particularly for inhibit, emotion control, shift, working memory, and monitor domains. Furthermore, depression moderated the abdominal overweight-GEC association (P = 0.032 for interaction term), especially for emotional control, working memory, and initiate dimensions. Moreover, we also found abdominal thinness was associated with the Metacognition Index problem (OR = 1.33, 95% CI 1.04-1.72), particularly for plan and monitor areas. CONCLUSIONS: Both abdominal overweight and thinness were associated with adolescent EF, and depression would be a modifiable target to improve EF in adolescents with abdominal overweight. Future longitudinal studies are needed to investigate the causal relationship between abdominal weight spectrum and EF, as well as the underlying mechanisms among adolescents suffering from depression.

10.
J Sleep Res ; 31(4): e13530, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-34904310

RESUMO

Sleep is vital for children's early socio-emotional development, particularly empathy. This study aimed to explore the associations between sleep and empathy in young preschoolers. A sample of 23,259 preschoolers (4.3 ± 0.3 years) at the entry year of preschool was recruited as part of the Shanghai Children's Health, Education and Lifestyle Evaluation-Preschool (SCHEDULE-P) study. Caregivers reported on child sleep, affective empathy, and cognitive empathy through the Children's Sleep Habits Questionnaire and the Griffith Empathy Measure. Ordinary least-square regression and quantile regression were performed for the associations between sleep and empathy. Sex differences were also investigated. Night sleep duration was negatively associated with affective empathy (ß = -0.35, p < 0.001), and positively associated with cognitive empathy (ß = 0.41, p < 0.001). Longer nap duration was associated with higher affective empathy (ß = 0.28, p < 0.001). Sleep disturbances were positively associated with affective empathy (ß = 0.04, p < 0.001) and negatively associated with cognitive empathy (ß = -0.09, p < 0.001). These associations were generally stronger in children at higher empathy quantiles and also those at the 10th cognitive empathy quantile. The associations between sleep and affective empathy were mainly contributed by girls, and were more common in boys in terms of cognitive empathy, particularly at the 10th and the 30th quantiles. In conclusion, longer night sleep duration and fewer sleep disturbances are associated with a more mature empathy pattern in young preschoolers. The associations are more prominent in children at the higher end of the empathy spectrum, and vary by sex. These findings highlight the importance to promote sleep health in young children for optimal socio-emotional development.


Assuntos
Empatia , Transtornos do Sono-Vigília , Criança , Pré-Escolar , China/epidemiologia , Emoções , Feminino , Humanos , Masculino , Sono , Transtornos do Sono-Vigília/complicações
11.
Asian Pac J Allergy Immunol ; 40(1): 55-64, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33274951

RESUMO

BACKGROUND: There is growing evidence that environmental exposure in early life is associated with the development of childhood allergic rhinitis. OBJECTIVE: To investigate whether polymorphisms in previously published genome wide association studies (GWAS) allergic disease loci are associated with childhood house dust mite-induced allergic rhinitis (HDM-AR) and interaction effects of genetic and environmental factors on it. METHODS: 156 cases diagnosed by HDM-AR and 173 controls were enrolled. Potential confounders were analyzed by using Logistic regression. Twenty-one single nucleotide polymorphisms (SNPs) of GWAS-related allergic diseases including EMSY-LRRC32, IL18R1, IL18RAP, IL13, IL4, HLA region, KIF3A were genopyped and analyzed using the improved multiplex ligation detection reaction (imLDR) technique in all the subjects. RESULTS: Only IL18R1_rs2287037 was associated with HDM-AR in children. After adjusting for several likely confounders, the protective TT genotype of IL18R1_rs2287037 was found in the population analyzed with the fittest recessive model. (adjusted odds ratio [aOR]: 0.44; 95% confidence interval [CI]: 0.21-0.95). The rs2287037_ TT might interact with early-life exclusive breastfeeding in the first 4 months (aOR: 0.33; 95%CI: 014-0.97) or full-term birth (aOR: 0.45; 95%CI: 0.19-0.95) exposure to decrease the risk of HDM-AR. CONCLUSIONS: These data suggest that IL18R1 polymorphism may play a role in controlling risk to HDM-AR and underline the importance of early environmental exposure into studies of genetic risk factors.


Assuntos
Estudo de Associação Genômica Ampla , Rinite Alérgica , Animais , Criança , China/epidemiologia , Exposição Ambiental/efeitos adversos , Humanos , Proteínas de Membrana/genética , Polimorfismo de Nucleotídeo Único , Pyroglyphidae , Rinite Alérgica/etiologia , Rinite Alérgica/genética
12.
Sleep Med ; 82: 165-171, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33933721

RESUMO

OBJECTIVES: Sleep disturbances are common in preschoolers, and profoundly affected by parenting. Grandparents are increasingly involved in childcare and have attracted worldwide attention for their potential impacts on child well-being. However, no studies have explored child sleep health within the context of grandparental care. We aimed to explore the association between grandparents as primary caregivers and children's sleep disturbances. METHODS: Participants included 20,324 preschoolers from the Shanghai Children's Health, Education and Lifestyle Evaluation-Preschool (SCHEDULE-P) in Shanghai, China. They were initially assessed in November 2016 and were reassessed in April 2018 and April 2019. Children's primary caregivers were collected at each survey. Sleep disturbances were assessed by the Children's Sleep Habits Questionnaire (CSHQ). RESULTS: At baseline, 84.4% of children had global sleep disturbances (CSHQ total score >41). Compared with parents, random-effects model indicated that grandparents as primary caregivers increased the adjusted odds ratio (OR) for children's global sleep disturbances by 30% (OR [95%CI]: 1.30 [1.21, 1.40]). To the specific domains of CSHQ, two-way repeated-measures ANOVA showed significant "caregiver transition" group × wave interaction in the behavioral sleep disturbances, such as "Bedtime Resistance" (p < 0.001). At each survey, children with grandparents as primary caregivers demonstrated significant higher behavioral sleep disturbances than their counterparts with parental care. CONCLUSIONS: Grandparental care is associated with increased sleep disturbances, particularly behavioral sleep disturbances, in preschoolers. Future studies should explore the underlying mechanisms and whether sleep programs targeting grandparents can decrease children's sleep disturbances.


Assuntos
Avós , Transtornos do Sono-Vigília , Pré-Escolar , China/epidemiologia , Estudos de Coortes , Humanos , Estudos Prospectivos , Sono , Transtornos do Sono-Vigília/epidemiologia , Inquéritos e Questionários
13.
Metab Eng ; 65: 99-110, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33744461

RESUMO

Advances in synthetic biology have enabled robust control of cell behavior by using tunable genetic circuits to regulate gene expression in a ligand-dependent manner. Such circuits can be used to direct the differentiation of pluripotent stem cells (PSCs) towards desired cell types, but rational design of synthetic gene circuits in PSCs is challenging due to the variable intracellular environment. Here, we provide a framework for implementing synthetic gene switches in PSCs based on combinations of tunable transcriptional, structural, and posttranslational elements that can be engineered as required, using the vanillic acid-controlled transcriptional activator (VanA) as a model system. We further show that the VanA system can be multiplexed with the well-established reverse tetracycline-controlled transcriptional activator (rtTA) system to enable independent control of the expression of different transcription factors in human induced PSCs in order to enhance lineage specification towards early pancreatic progenitors. This work represents a first step towards standardizing the design and construction of synthetic gene switches for building robust gene-regulatory networks to guide stem cell differentiation towards a desired cell fate.


Assuntos
Células-Tronco Pluripotentes Induzidas , Células-Tronco Pluripotentes , Diferenciação Celular/genética , Redes Reguladoras de Genes/genética , Genes Sintéticos , Humanos
14.
J Affect Disord ; 287: 8-14, 2021 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-33761325

RESUMO

BACKGROUND: There are increasing concerns that the coronavirus disease (COVID-19) pandemic will disproportionately affect socioeconomically disadvantaged children. However, there lacks empirical evidence on socioeconomic inequalities in child mental health and associated factors. METHODS: We conducted a population-based online survey in 21,526 children in China, when children were confined at home for nearly two months during the pandemic. We assessed child mental health problems with the Strengths and Difficulties Questionnaire (SDQ). Parental education level and provincial gross domestic product (GDP) per capita were treated as proxies for individual- and population-level socioeconomic status (SES), respectively. Lifestyle and family environment factors included sleep disturbances, physical activity, screen time, primary caregiver, parental mental health, and harsh parenting. RESULTS: Of the children, 32.31% demonstrated mental health problems. Parental education from the highest (undergraduate and above) to the lowest (middle school and below) increased the adjusted odds ratio(aOR) for child mental health problems by 42% (aOR, 1.42; 95% CI, 1.29-1.57); provincial GDP per capita (RMB) from the highest (>¥100K) to the lowest (≤¥70K) increased aOR by 41% (aOR, 1.41; 95% CI%, 1.28-1.55). Sleep disturbances, physical activity <1 h/day, media exposure ≥2 h/day, non-parental care, poor parental mental health, and harsh parenting were independently associated with increased child mental health problems, regardless of SES. LIMITATIONS: The potential sampling bias, subjective measures, and the cross-sectional design are the main limitations. CONCLUSION: The first evidence from China suggests socioeconomic inequality in child mental health during the pandemic. As unhealthy lifestyle and unfavorable family environment are contributory factors, prioritized interventions are needed to reduce socioeconomic inequality in child mental health problems.


Assuntos
COVID-19 , Coronavirus , Criança , China/epidemiologia , Estudos Transversais , Humanos , Saúde Mental , Pandemias , SARS-CoV-2 , Fatores Socioeconômicos , Inquéritos e Questionários
15.
Appetite ; 162: 105174, 2021 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-33636216

RESUMO

Previous studies have suggested that infant rapid weight change can be associated with an increased weight later in life. However, the weight change trajectory in early life over time and which childhood lifestyle behaviors may modify the risk of rapid weight change have not been characterized. Using our ongoing birth cohort study, we have addressed these issues. Nine follow-up time points (birth, 3, 6, 9, 12, 18, 24, 36, and 48 months) were used to calculate the change between two adjacent weight-for-age z-scores (WAZ-change), and then WAZ-change trajectories were defined via group-based trajectory modeling. The solitary, independent and combined effects of WAZ-change trajectories and each lifestyle factor (eating behaviors, physical activity, media exposure time and total sleep duration) on childhood adiposity measures at age 4 years were determined using multivariate regression analysis. Overall, 84 (38%) children had a steady growth trajectory from birth to 4 years, while the other 137 (62%) children had an early infancy rapid growth trajectory, particularly in the first three months. Compared to children with steady growth, children with early infancy rapid growth had a significantly higher body mass index, waist circumference, and subcutaneous fat. Moreover, weight change trajectory and three eating behaviors (i.e. food responsiveness, satiety responsiveness and food fussiness), not only had independent effects, but also combined (synergistic) effects on the majority of adiposity measures. Our results extend the current literature and provide a potentially valuable model to aid clinicians and health professionals in designing early-life interventions targeting specific populations, specific ages and specific lifestyle behaviors to prevent childhood overweight/obesity.


Assuntos
Trajetória do Peso do Corpo , Obesidade Infantil , Adiposidade , Peso ao Nascer , Índice de Massa Corporal , Criança , Pré-Escolar , Estudos de Coortes , Comportamento Alimentar , Feminino , Humanos , Lactente , Fatores de Risco
17.
Int J Speech Lang Pathol ; 23(4): 372-381, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-33059481

RESUMO

PURPOSE: To fulfil the needs of assessment tools in the Chinese population, we adapted the LENA Developmental Snapshot, a parent survey that measures early language and communication development in English-speaking children. We reported the psychometric properties of the adapted questionnaire and evaluated the metric and functional equivalence between the adapted and the original instruments. METHOD: The Snapshot was translated into Chinese and reviewed by an expert panel. English-specific items (e.g. past tense, plural) were mapped onto functionally similar Mandarin vocabulary and structures. The questionnaire was administered to 1300 families with children ages 2-48 months. The Bayley Scales of Infant Development was administered to a subsample. RESULT: Scores on the adapted questionnaire showed age-related increases in the 7-36 month age range and correlated with scores on the Chinese Bayley. The questionnaire showed high internal consistency and split-half reliability. Comparison with the US norm revealed slightly lower performance in the current sample. Adaptations of English-specific items resulted in functionally equivalent targets. CONCLUSION: Despite differences in linguistic roots, the Chinese adaption of the LENA Snapshot captured developmental changes in children's language and communication abilities. Additional norming and validation efforts are needed in a more representative sample.


Assuntos
Desenvolvimento da Linguagem , Idioma , Criança , Pré-Escolar , China , Humanos , Lactente , Psicometria , Reprodutibilidade dos Testes , Inquéritos e Questionários
18.
Front Pediatr ; 9: 805575, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-35155316

RESUMO

Mutations in the human O-phosphoseryl-tRNA:selenocysteinyl-tRNA synthase gene (SEPSECS) are associated with progressive cerebello-cerebral atrophy (PCCA), also known as pontocerebellar hypoplasia type 2D (PCH2D). Early-onset profound developmental delay, progressive microcephaly, and hypotonia that develops toward severe spasticity have been previously reported with SEPSECS mutations. Herein we report a case with severe global developmental delay, myogenic changes in the lower limbs, and insomnia, but without progressive microcephaly and brain atrophy during infancy and toddlerhood in a child harboring the SEPSECS missense variant c.194A>G (p. Asn65Ser) and a novel splicing mutation c.701+1G>A. With these findings we communicate the first Chinese SEPSECS mutant case, and our report indicates that SEPSECS mutations can give rise to a milder phenotype.

19.
Sleep Med ; 77: 376-383, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-32839086

RESUMO

OBJECTIVES: To study the impact of maternal sleep in late pregnancy on birth weight (BW) and leptin and lipid levels in umbilical cord blood. STUDY DESIGN: A total of 277 healthy and singleton pregnancy women were recruited for participation in the Shanghai Sleep Birth Cohort Study (SSBC) during their 36-38 weeks of pregnancy, from May 2012 to July 2013. Maternal night sleep time (NST), sleep efficiency (SE), sleep onset latency (SOL) and the percentage of wake after sleep onset (WASO) in NST and midpoint of sleep (MSF) were measured by actigraphy for seven consecutive days. The leptin and lipid levels were determined in cord blood samples collected from the umbilical vein immediately after delivery. Birth information (birth weight, gender, delivery type, etc.) was extracted from medical records. A multivariable linear regression model was applied to examine the effect of maternal sleep in late pregnancy on newborn leptin and lipid levels in umbilical cord blood. RESULTS: A total of 177 women and their infants were included in the analysis. Maternal mean NST was 7.03 ± 1.10 h in late pregnancy, and 48% had a shorter sleep time (NST < 7 h). The average maternal SE was 72.54% ± 9.66%. The mean percentage WASO/NST was 21.62% ± 9.98%; the average MSF was about 3:34 (0:53); and the SOL was 46.78 ± 36.00 min. After adjustment for confounders, both maternal NST and SE were found to be significantly associated with triglyceride levels (ß = -0.219, p = 0.006; ß = -0.224, p = 0.006) in umbilical cord blood; and maternal NST was also observed to have positive association with newborn leptin levels (ß = 0.146, p = 0.047). However, we did not find significant association between other maternal sleep parameters in late pregnancy and leptin and lipid levels and birth weight. CONCLUSIONS: Short sleep duration and poor sleep quality during late pregnancy were associated with newborn leptin and lipid levels, and efforts on improving maternal sleep during late pregnancy should be advocated for children's health.


Assuntos
Sangue Fetal , Leptina , Criança , China , Estudos de Coortes , Feminino , Humanos , Lactente , Recém-Nascido , Lipídeos , Gravidez , Sono
20.
Paediatr Perinat Epidemiol ; 35(2): 257-268, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33337549

RESUMO

BACKGROUND: Sleep disturbances in women occur frequently throughout pregnancy. Previous studies have demonstrated that the increasing incidence of physiological and psychological illness is concurrent with increasing sleep deprivation and poor sleep quality in adults and children. OBJECTIVES: The Shanghai Sleep Birth Cohort Study (SSBCS) was established to examine the effect of sleep disturbances during the third trimester on emotional regulation of mothers; to assess the effect of maternal sleep during pregnancy on the growth and development of children; and to explore the influence of children's sleep characteristics on physical and social-emotional development. POPULATION: The study was conducted in the Renji Hospital in Pudong New District, Shanghai from May 2012 to July 2013. Women and their newborns who met the inclusion criteria and agreed to participate in this study were recruited to the SSBCS. METHODS: The follow-up visits for children were conducted at the age of 42 days, 3, 6, 9, 12, 18, and 24 months, and 3, 4, and 6 years. Data on demographic factors, physical examination, sleep assessment, developmental and psychiatric assessment, diet records, and biological samples were collected throughout the study. PRELIMINARY RESULTS: A total of 277 pregnant women were recruited to the study; the response rate was 64.3%. 37.9% of the pregnant women had poor sleep quality and 12.0% suffered from depression. Infant sleep patterns changed during the first year of life, but most sleep characteristics showed little variation from 6 to 12 months. CONCLUSIONS: The SSBCS is an on-going prospective cohort study with follow-up to 6 years. The detailed data on demographic factors, sleep assessment, physical examinations, neurodevelopmental and psychiatric assessment, diet records, and biological samples make this research platform an important resource for examining the potential effects of sleep characteristics on both maternal and child health.


Assuntos
Mães , Sono , Adulto , Criança , China/epidemiologia , Estudos de Coortes , Feminino , Humanos , Lactente , Recém-Nascido , Gravidez , Estudos Prospectivos
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