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DNA-based therapeutics have emerged as a revolutionary approach for addressing the treatment gap in rare inherited conditions by targeting the fundamental genetic causes of disease. Charcot-Marie-Tooth (CMT) disease, a group of inherited neuropathies, represents one of the most prevalent Mendelian disease groups in neurology and is characterized by diverse genetic etiology. Axonal forms of CMT, known as CMT2, are caused by dominant mutations in over 30 different genes which lead to degeneration of lower motor neuron axons. Recent advances in antisense oligonucleotide (ASO) therapeutics have shown promise in targeting neurodegenerative disorders. Here we elucidate pathomechanistic changes contributing to variant specific molecular phenotypes in CMT2E, caused by a single nucleotide substitution (p.N98S) in the neurofilament light chain gene (NEFL). We used a patient-derived pluripotent stem cell (iPSC)-induced motor neuron model, which recapitulates several cellular and biomarker phenotypes associated with CMT2E. Using an ASO treatment strategy targeting a heterozygous gain-of-function variant, we aimed to resolve molecular phenotypic changes observed in the CMT2E p.N98S subtype. To determine ASO therapeutic potential, we employed our treatment strategy in iPSC-derived motor neurons and used established as well as novel biomarkers of peripheral nervous system axonal degeneration. Our findings have demonstrated a significant decrease in clinically relevant biomarkers of axonal degeneration, presenting the first clinically viable genetic therapeutic for CMT2E. Similar strategies could be used to develop precision medicine approaches for otherwise untreatable gain of function inherited disorders.
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BACKGROUND: Carvedilol improves cardiac function in patients with heart failure but remains untested as cardioprotective therapy in long-term childhood cancer survivors (ie, those who have completed treatment for childhood cancer and are in remission) at risk for heart failure due to high-dose anthracycline exposure. We aimed to evaluate the activity and safety of low-dose carvedilol for heart failure risk reduction in childhood cancer survivors at highest risk for heart failure. METHODS: PREVENT-HF was a randomised, double-blind, phase 2b trial done at 30 hospitals in the USA and Canada. Patients were eligible if they had any cancer diagnosis that resulted in at least 250 mg/m2 cumulative exposure to anthracycline by age 21 years; completed their cancer treatment at least 2 years previously; an ejection fraction of at least 50% or fractional shortening of at least 25%, or both; and bodyweight of at least 40 kg. Patients were randomly assigned (1:1) with automated computer-generated permuted block randomisation (block size of 4), stratified by age at diagnosis, time since diagnosis, and history of chest-directed radiotherapy, to carvedilol (up-titrated from 3·125 g per day to 12·5 mg per day) or placebo orally for 2 years. Participants, staff, and investigators were masked to study group allocation. The primary endpoint was to establish the effect of carvedilol on standardised left ventricular wall thickness-dimension ratio Z score (LVWT/Dz). Treatment effects were analysed with a linear mixed-effects model for normally distributed data with a linear time effect and testing the significance of treatment*time interaction in the modified intention-to-treat (mITT) cohort (ie, all randomly assigned participants who had a baseline and at least one subsequent echocardiogram measurement). Safety was assessed in the ITT population (ie, all randomly assigned participants). This trial was registered with ClinicalTrials.gov, NCT027175073, and enrolment and follow-up are complete. FINDINGS: Between July 3, 2012, and June 22, 2020, 196 participants were enrolled, of whom 182 (93%) were eligible and randomly assigned to either carvedilol (n=89) or placebo (n=93; ITT population). Median age was 24·7 years (IQR 19·6-36·6), 91 (50%) participants were female, 91 (50%) were male, and 119 (65%) were non-Hispanic White. As of data cutoff (June 10, 2022), median follow-up was 725 days (IQR 378-730). 151 (n=75 in the carvedilol group and n=76 in the placebo group) of 182 participants were included in the mITT population, among whom LVWT/Dz was similar between the two groups (-0·14 [95% CI -0·43 to 0·16] in the carvedilol group vs -0·45 [-0·77 to -0·13] in the placebo group; difference 0·31 [95% CI -0·10 to 0·73]; p=0·14). Two (2%) of 89 patients in the carvedilol group two adverse events of grade 2 or higher (n=1 shortness of breath and n=1 arthralgia) and none in the placebo group. There were no adverse events of grade 3 or higher and no deaths. INTERPRETATION: Low-dose carvedilol appears to be safe in long-term childhood cancer survivors at risk for heart failure, but did not result in significant improvement of LVWT/Dz compared with placebo. These results do not support the use of carvedilol for secondary heart failure prevention in anthracycline-exposed childhood cancer survivors. FUNDING: National Cancer Institute, Leukemia & Lymphoma Society, St Baldrick's Foundation, Altschul Foundation, Rally Foundation, American Lebanese Syrian Associated Charities.
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Sobreviventes de Câncer , Insuficiência Cardíaca , Neoplasias , Adulto , Criança , Feminino , Humanos , Masculino , Adulto Jovem , Antraciclinas/efeitos adversos , Carvedilol/uso terapêutico , Método Duplo-Cego , Neoplasias/tratamento farmacológico , Resultado do TratamentoRESUMO
BACKGROUND: Patients undergoing autologous hematopoietic cell transplantation (HCT) have a >2-fold risk of developing cardiovascular disease (CVD; heart failure, myocardial infarction, and stroke), compared to the general population. Coronary artery calcium (CAC) is predictive of CVD in nononcology patients but is not as well studied in patients who underwent HCT and survivors of HCT.The objective of this study was to examine the association between CAC and CVD risk and outcomes after HCT in patients with lymphoma. METHODS: This was a retrospective cohort study of 243 consecutive patients who underwent a first autologous HCT for lymphoma between 2009 and 2014. CAC (Agatston score) was determined from chest computed tomography obtained <60 days from HCT. Multivariable Cox regression analysis was used to calculate hazard ratio (HR) estimates and 95% confidence intervals (CIs), adjusted for covariates (age, conventional risk factors [e.g., hypertension and dyslipidemia], and cancer treatment). RESULTS: The median age at HCT was 55.7 years (range, 18.5-75.1 years), 59% were male, and 60% were non-Hispanic White. The prevalence of CAC was 37%. The 5-year CVD incidence for the cohort was 12%, and there was an incremental increase in the incidence according to CAC score: 0 (6%), 1-100 (20%), and >100 (32%) (p = .001). CAC was significantly associated with CVD risk (HR, 3.0; 95% CI, 1.2-7.5) and worse 5-year survival (77% vs. 50%; p < .001; HR, 2.0; 95% CI, 1.1-3.4), compared to those without CAC. CONCLUSIONS: CAC is independently associated with CVD and survival after HCT. This highlights the importance of integrating readily available imaging information in risk stratification and decision-making in patients undergoing HCT, which sets the stage for strategies to optimize outcomes after HCT.
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Doenças Cardiovasculares , Transplante de Células-Tronco Hematopoéticas , Linfoma , Transplante Autólogo , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Adulto , Estudos Retrospectivos , Idoso , Linfoma/terapia , Adulto Jovem , Adolescente , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/epidemiologia , Vasos Coronários/diagnóstico por imagem , Vasos Coronários/patologia , Vasos Coronários/metabolismo , Fatores de Risco , Cálcio/metabolismo , Doença da Artéria Coronariana/epidemiologia , IncidênciaRESUMO
BACKGROUND: Amyotrophic lateral sclerosis (ALS) leads to paralysis and death by progressive degeneration of motor neurons. Recently, specific gain-of-function mutations in SPTLC1 were identified in patients with juvenile form of ALS. SPTLC2 encodes the second catalytic subunit of the serine-palmitoyltransferase (SPT) complex. METHODS: We used the GENESIS platform to screen 700 ALS whole-genome and whole-exome data sets for variants in SPTLC2. The de-novo status was confirmed by Sanger sequencing. Sphingolipidomics was performed using liquid chromatography and high-resolution mass spectrometry. RESULTS: Two unrelated patients presented with early-onset progressive proximal and distal muscle weakness, oral fasciculations, and pyramidal signs. Both patients carried the novel de-novo SPTLC2 mutation, c.203T>G, p.Met68Arg. This variant lies within a single short transmembrane domain of SPTLC2, suggesting that the mutation renders the SPT complex irresponsive to regulation through ORMDL3. Confirming this hypothesis, ceramide and complex sphingolipid levels were significantly increased in patient plasma. Accordingly, excessive sphingolipid production was shown in mutant-expressing human embryonic kindney (HEK) cells. CONCLUSIONS: Specific gain-of-function mutations in both core subunits affect the homoeostatic control of SPT. SPTLC2 represents a new Mendelian ALS gene, highlighting a key role of dysregulated sphingolipid synthesis in the pathogenesis of juvenile ALS. Given the direct interaction of SPTLC1 and SPTLC2, this knowledge might open new therapeutic avenues for motor neuron diseases.
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Esclerose Lateral Amiotrófica , Serina C-Palmitoiltransferase , Humanos , Esclerose Lateral Amiotrófica/genética , Ceramidas , Mutação com Ganho de Função , Mutação/genética , Serina C-Palmitoiltransferase/genética , Serina C-Palmitoiltransferase/química , EsfingolipídeosRESUMO
BACKGROUND: Lung cancer (LC), characterized by high incidence and mortality rates, presents a significant challenge in oncology. Despite advancements in treatments, early detection remains crucial for improving patient outcomes. The accuracy of screening for LC by detecting volatile organic compounds (VOCs) in exhaled breath remains to be determined. METHODS: Our systematic review, following PRISMA guidelines and analyzing data from 25 studies up to October 1, 2023, evaluates the effectiveness of different techniques in detecting VOCs. We registered the review protocol with PROSPERO and performed a systematic search in PubMed, EMBASE and Web of Science. Reviewers screened the studies' titles/abstracts and full texts, and used QUADAS-2 tool for quality assessment. Then performed meta-analysis by adopting a bivariate model for sensitivity and specificity. RESULTS: This study explores the potential of VOCs in exhaled breath as biomarkers for LC screening, offering a non-invasive alternative to traditional methods. In all studies, exhaled VOCs discriminated LC from controls. The meta-analysis indicates an integrated sensitivity and specificity of 85% and 86%, respectively, with an AUC of 0.93 for VOC detection. We also conducted a systematic analysis of the source of the substance with the highest frequency of occurrence in the tested compounds. Despite the promising results, variability in study quality and methodological challenges highlight the need for further research. CONCLUSION: This review emphasizes the potential of VOC analysis as a cost-effective, non-invasive screening tool for early LC detection, which could significantly improve patient management and survival rates.
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Testes Respiratórios , Detecção Precoce de Câncer , Neoplasias Pulmonares , Compostos Orgânicos Voláteis , Humanos , Compostos Orgânicos Voláteis/análise , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/metabolismo , Detecção Precoce de Câncer/métodos , Testes Respiratórios/métodos , Expiração , Sensibilidade e Especificidade , Biomarcadores Tumorais/análise , Biomarcadores Tumorais/metabolismoRESUMO
BACKGROUND: Given the increasing prevalence of obesity in young people in Ecuador, there is a need to understand the factors associated with this condition. The aim of this study was to assess the prevalence of obesity in Ecuadorian children and adolescents aged 5-17 years and identify its associated sociodemographic and lifestyle factors. METHODS: This cross-sectional study was conducted using data from the Encuesta Nacional de Salud y Nutrición (ENSANUT-2018). The final sample consisted of 11,980 participants who provided full information on the variables of interest. RESULTS: The prevalence of obesity was 12.7%. A lower odd of having obesity was observed for adolescents; for those with a breadwinner with an educational level in middle/high school or higher; for each additional day with 60 or more minutes of daily moderate-to-vigorous physical activity; and for those with greater daily vegetable consumption (one, two, or three or more servings). Conversely, there were greater odds of obesity in participants from families with medium, poor, and very poor wealth and those from the coast and insular region. CONCLUSIONS: The high prevalence of obesity in Ecuadorian children and adolescents is a public health concern. Sociodemographic and lifestyle behavior differences in young people with obesity should be considered when developing specific interventions. IMPACT: As the prevalence of obesity among children and adolescents increases in Latin America, with a particular focus on Ecuador, it becomes crucial to delve into the factors linked to this condition and identify the most successful strategies for its mitigation. The elevated prevalence of obesity among young individuals in Ecuador raises significant public health concerns. To develop targeted interventions, it is crucial to account for sociodemographic variables and lifestyle behaviors that contribute to obesity in this population.
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Auditory steady-state response underlying gamma oscillations (gamma-ASSR) have been explored in patients with major depressive disorder (MDD), while ignoring the spatiotemporal dynamic characteristics. This study aims to construct dynamic directed brain networks to explore the disruption of spatiotemporal dynamics underlying gamma-ASSR in MDD. This study recruited 29 MDD patients and 30 healthy controls for a 40 Hz auditory steady-state evoked experiment. The propagation of gamma-ASSR was divided into early, middle, and late time interval. Partial directed coherence was applied to construct dynamic directed brain networks based on graph theory. The results showed that MDD patients had lower global efficiency and out-strength in temporal, parietal, and occipital regions over three time intervals. Additionally, distinct disrupted connectivity patterns occurred in different time intervals with abnormalities in the early and middle gamma-ASSR in left parietal regions cascading forward to produce dysfunction of frontal brain regions necessary to support gamma oscillations. Furthermore, the early and middle local efficiency of frontal regions were negatively correlated with symptom severity. These findings highlight patterns of hypofunction in the generation and maintenance of gamma-band oscillations across parietal-to-frontal regions in MDD patients, which provides novel insights into the neuropathological mechanism underlying gamma oscillations associated with aberrant brain network dynamics of MDD.
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Transtorno Depressivo Maior , Humanos , Encéfalo , Mapeamento Encefálico , Lobo Parietal , Comunicação , Imageamento por Ressonância Magnética/métodosRESUMO
The purpose of this systematic review was to synthesise the evidence for the association of adherence to the 24-h movement guidelines with academic-related outcomes in children and adolescents. This systematic review was based on the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) statement. PubMed, PsycINFO, Scopus, WOS, SPORTDiscus, and EMBASE were searched from their inception to 12 December 2023. The Joanna Briggs Institute (JBI) Critical Appraisal Checklist was used to assess the risk of bias of included studies. In total, 4326 records were identified through database searches; 10 articles met the inclusion criteria and were included in this systematic review. There were eight cross-sectional studies and two longitudinal studies; the main academic-related outcomes were academic achievement and cognitive function. A small association between adherence to all three recommendations and academic achievement (k = 5, r = 0.17, 95% CI = 0.10-0.24, I2 = 49%) was found compared to those who did not adhere to any recommendations. Conclusion: Findings from this systematic review and meta-analysis reveal a small association between adherence to all three recommendations and greater academic achievement in children and adolescents. Nevertheless, it is imperative to underscore the need for more studies to establish robust evidence underpinning this relationship. Trial registration: PROSPERO (CRD42021295403). What is Known: ⢠Regular physical activity, reduced screen time, and optimal sleep duration are independently associated with improved academic-related outcomes in children and adolescents. ⢠The associations between adherence to the 24-h movement guidelines and academic-related outcomes in children and adolescents have not been quantitatively synthesised. What is New: ⢠There is a small but positive association between adherence to all three recommendations of the 24-h movement guidelines and greater academic achievement in children and adolescents. ⢠Further well-designed research is needed to focus on academic achievement, cognitive function and classroom behaviours in young individuals.
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Sucesso Acadêmico , Humanos , Adolescente , Criança , Exercício Físico , Fidelidade a Diretrizes/estatística & dados numéricos , CogniçãoRESUMO
BACKGROUND: Pneumonia is a common lower respiratory tract infection, and early diagnosis is crucial for timely treatment and improved prognosis. Traditional diagnostic methods for pneumonia, such as chest imaging and microbiological examinations, have certain limitations. Exhaled volatile organic compounds (VOCs) detection, as an emerging non-invasive diagnostic technique, has shown potential application value in pneumonia screening. METHOD: A systematic search was conducted on PubMed, Embase, Cochrane Library, and Web of Science, with the retrieval time up to March 2024. The inclusion criteria were diagnostic studies evaluating exhaled VOCs detection for the diagnosis of pneumonia, regardless of the trial design type. A meta-analysis was performed using a bivariate model for sensitivity and specificity. RESULTS: A total of 14 diagnostic studies were included in this meta-analysis. The pooled results demonstrated that exhaled VOCs detection had a combined sensitivity of 0.94 (95% CI: 0.92-0.95) and a combined specificity of 0.83 (95% CI: 0.81-0.84) in pneumonia screening, with an area under the summary receiver operating characteristic (SROC) curve (AUC) of 0.96. The pooled diagnostic odds ratio (DOR) was 104.37 (95% CI: 27.93-390.03), and the pooled positive and negative likelihood ratios (LR) were 8.98 (95% CI: 3.88-20.80) and 0.11 (95% CI: 0.05-0.22), indicating a high diagnostic performance. CONCLUSION: This study highlights the potential of exhaled VOCs detection as an effective, non-invasive screening method for pneumonia, which could facilitate future diagnosis in pneumonia. Further high-quality, large-scale studies are required to confirm the clinical utility of exhaled VOCs detection in pneumonia screening. STUDY REGISTRATION: PROSPERO, Review no. CRD42024520498.
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BACKGROUND: Adherence to the 24-h movement guidelines is associated with various health benefits, but given the novelty of these integrative recommendations, little is known about year-to-year trends in guideline adherence in adolescents. This study investigated trends of adherence to the 24-h movement guidelines among US adolescents. METHODS: Data from 2011 to 2019 cycles of the Youth Risk Behavior Surveillance System were used, which included 62 589 US adolescents aged 14-17 years (female: unweighted sample size = 31 876, 51%; weighted% = 50.1%). Participants self-reported their demographic information (i.e., sex, age, race/ethnicity), physical activity, screen time and sleep duration. Meeting the 24-h movement guidelines was operationalized as simultaneously engaging in 60 min or more of moderate-to-vigorous physical activity, no more than 2 h of screen time, and 8-10 h of sleep per day. Trend analysis was used to examine the secular changes in adherence to the integrated guidelines from 2011 to 2019. RESULTS: Downward trends in adherence to the 24-h movement guidelines were observed among adolescents from 2011 (3.6%) to 2019 (2.6%). After stratification by sex, age, and race/ethnicity, similar downward trends in the guideline adherence were observed in females and Black/African American adolescents. The lowest prevalence of meeting the individual guidelines was for the PA guidelines (25.6%). Movement guideline adherence was consistently lowest among females, older adolescents, and those who identified as Black/African American. CONCLUSIONS: Adherence to the 24-h movement guidelines has declined among US adolescents over the past decade. Interventions should prioritize an integrative approach that could increase concurrent adherence to each of the 24-h movement guideline, particularly among female, older and minority adolescents.
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Exercício Físico , Comportamento Sedentário , Humanos , Adolescente , Feminino , Estudos Transversais , Autorrelato , Sono , Fidelidade a DiretrizesRESUMO
There is some, albeit inconsistent, evidence supporting sex differences in preschoolers' motor competence (MC), with these observations not uniform when analyzed by age, and cultural groups. Thus, this study examined sex differences across ages in 3- to 5-year-old children's MC. A cross-country pooled sample of 6241 children aged 3-5 years (49.6% girls) was assessed for MC using the Test of Gross Motor Development-2nd/3rd edition, and children were categorized into groups of age in months. Multiple linear regression models and predictive margins were calculated to explore how sex and age in months affect scores of MC (i.e., locomotor and ball skills), with adjustments for country and BMI. The Chow's Test was used to test for the presence of a structural break in the data. Significant differences in favor of girls were seen at 57-59 and 66-68 months of age for locomotor skills; boys performed better in ball skills in all age periods, except for 42-44 and 45-47 months of age. The higher marginal effects were observed for the period between 45-47 and 48-50 months for locomotor skills (F = 30.21; and F = 25.90 for girls and boys, respectively), and ball skills (F = 19.01; and F = 42.11 for girls and boys, respectively). A significantly positive break point was seen at 45-47 months, highlighting the age interval where children's MC drastically improved. The identification of this breakpoint provides an evidence-based metric for when we might expect MC to rapidly increase, and an indicator of early delay when change does not occur at that age.
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Destreza Motora , Humanos , Destreza Motora/fisiologia , Feminino , Masculino , Pré-Escolar , Estudos Transversais , Fatores Sexuais , Fatores Etários , Desenvolvimento Infantil/fisiologia , Modelos LinearesRESUMO
Many cellular processes occur out of equilibrium. This includes site-specific unwinding in supercoiled DNA, which may play an important role in gene regulation. Here, we use the Convex Lens-induced Confinement (CLiC) single-molecule microscopy platform to study these processes with high-throughput and without artificial constraints on molecular structures or interactions. We use two model DNA plasmid systems, pFLIP-FUSE and pUC19, to study the dynamics of supercoiling-induced secondary structural transitions after perturbations away from equilibrium. We find that structural transitions can be slow, leading to long-lived structural states whose kinetics depend on the duration and direction of perturbation. Our findings highlight the importance of out-of-equilibrium studies when characterizing the complex structural dynamics of DNA and understanding the mechanisms of gene regulation.
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DNA Super-Helicoidal , DNA , DNA/genética , DNA Super-Helicoidal/genética , Cinética , Conformação de Ácido Nucleico , Plasmídeos/genética , Imagem Individual de MoléculaRESUMO
BACKGROUND: Given the growing evidence on the health benefits associated with physical literacy (PL), it is necessary to develop sound measures to assess the levels of PL in children. The Physical Literacy in Children Questionnaire (PL-C Quest) is the first self-report pictorial-based scale to assess children's perceived PL. It has good validity and reliability in Australian children aged 7 to 12 years, but little is known in younger children and in other cultural contexts. The aim of this study was to examine the validity and reliability in an expanded age range. METHODS: A total of 1,870 Chinese children (girls, n = 871; 46.6%), aged 4 to 12 years (M = 8.07 ± 2.42) participated in validity testing. Structural equation modeling with the Weighted Least Squares with Mean and Variance approach was used to assess construct validity. The hypothesized theoretical model used the 30 items and four hypothesized factors: physical, psychological, social and cognitive capabilities. Multigroup confirmatory factor analysis was used to assess sex and age group (4-6 years, 7-9 years and 10-12 years) measurement invariance. Internal consistency analyses were conducted using polychoric alpha. A random subsample (n = 262) was selected to determine test-retest reliability using Intra-Class Correlations (ICC). RESULTS: All items except one (moving with equipment-skateboarding) loaded on sub-domains with λ > 0.45. The hypothesized model had a good fit (CFI = 0.954, TLI = 0.950, RMSEA = 0.042), with measurement equivalence across sex and age groups separately. Internal consistency values were good to excellent (overall: α = 0.94; physical: α = 0.86; psychological: α = 0.83; social: α = 0.81; cognitive: α = 0.86). Test-retest reliability was adequate to excellent (overall: ICC = 0.90, physical: ICC = 0.86, psychological: ICC = 0.75, social: ICC = 0.71, cognitive: ICC = 0.72). CONCLUSION: The Chinese version of the PL-C Quest is valid and reliable for testing the self-reported PL of Chinese children aged 4 to 12. This study provides the first evidence of validity for this tool in children aged 4-6 years and also evidence that the PL-C Quest would be a meaningful instrument to assess PL in Chinese children.
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Alfabetização , Criança , Feminino , Humanos , Austrália , Psicometria , Reprodutibilidade dos Testes , Autorrelato , Inquéritos e Questionários , Masculino , Pré-EscolarRESUMO
This study aimed to examine the preliminary efficacy and feasibility of implementing a tailored version of the MASTER coach education programme in Chinese primary schools to support physical education (PE) teachers' basketball lesson design and delivery. A total of 20 primary schools in Beijing, China were recruited, with one PE teacher and their class (N = 715 students aged 10-13 yrs) from each school included in the study and randomly allocated to the MASTER intervention (n = 10) or control group (n = 10). Compared to the control group, a significant difference was observed in the MASTER group for the proportion of playing-form activities delivered during PE (27.65, 95% CI [20.27, 35.03]) and for teachers' perceptions of confidence (23.92, 95% CI [15.87, 31.92]) and competence (24.12, 95% CI [10.28, 24.71]) to teach. Significant differences between groups were observed for students' perceived athletic competence (3.56%; 95% CI [3.15, 3.96]), enjoyment (11.83%; 95% CI [10.98, 12.69]), well-being (8.51%; 95% CI [7.02, 10.00]), intrinsic motivation (+0.74%; 95% CI [0.30, 1.17]), introjected motivation (-2.24%; 95% CI [-2.77, -1.70]), and external motivation (-0.49%; 95% CI [-0.90, -0.08]). The MASTER programme was effective in improving teaching practices in Chinese primary schools, and in facilitating improvements in teacher and student outcomes.
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Basquetebol , Humanos , Educação Física e Treinamento , Projetos Piloto , Instituições Acadêmicas , Estudantes , Motivação , Professores Escolares , EnsinoRESUMO
OBJECTIVE: Emerging evidence suggests that meeting the 24-h movement guidelines is associated with optimal mental health. However, there remains some uncertainty regarding this association in children. Therefore, this study aimed to examine the association between meeting the 24-h movement guidelines and psychosocial health in children. METHODS: A cross-sectional study design was employed to investigate 2005 children aged 9-12 years from four districts of Shanghai, China. The 24-h movement behaviours were assessed using selected items from the Health Behaviour in School-aged Children (HBSC) survey questionnaire. Children's self-rated psychosocial health was evaluated using the Strengths or Difficulties Questionnaire (SDQ). Generalised Linear Models with the ordinal logistic module were employed to analyse the association between meeting the 24-h movement guidelines and psychosocial health. RESULTS: The overall prevalence of meeting all three 24-h movement recommendations was 10.2%. Among children, 7.9% of them exhibited abnormal total difficulties, with a notable difference between sex (boys: 11.2%, girls: 7.0%, p = 0.001). Meeting all three 24-h movement behaviour recommendations was associated with reduced total difficulties, emotional symptoms, conduct problems, hyperactivity and peer problems. Furthermore, a dose-response association was observed, indicating that meeting a greater number of 24-h movement behaviour recommendations was associated with enhanced psychosocial health, particularly in boys. CONCLUSION: The findings of this study highlight the positive association between meeting the 24-h movement guidelines and psychosocial health in children. Notably, meeting more of these recommendations was associated with a lower likelihood of experiencing psychosocial problems, with greater benefits observed in boys compared with girls.
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Transtornos Mentais , Masculino , Criança , Feminino , Humanos , Estudos Transversais , China , Transtornos Mentais/psicologia , Inquéritos e Questionários , Saúde Mental , Sono/fisiologiaRESUMO
BACKGROUND: Proteins and anionic octenyl succinic anhydride (OSA)-modified starch (OSA-starch) are common ingredients in food systems. The interactions between OSA-starch and protein are found to alter the structural and functional properties of the protein-OSA-starch complexes. In this regard, the close understanding of the relationship among the molecular interactions between whey protein isolate (WPI) and OSA-high amylose corn starch (HAS), structure changes and rheological, digestibility and release properties of WPI-OSA-HAS was investigated. RESULTS: The molecular interactions of WPI-OSA-HAS were significant for increasing the surface rough, solubility, storage modulus and loss modulus, but decreasing the R1047/1022 values. For the nutritional evaluation, the anti-digestibility of WPI-OSA-HAS was enhanced with increased resistant starch + slowly digestible starch contents and decreased equilibrium hydrolysis percentage and kinetic constant. During the digestion, part of the starch granule, OSA groups and WPI were lost, but the loss was lower than for OSA-HAS. Furthermore, the results of curcumin-loaded WPI-OSA-HAS in simulated gastrointestinal fluids demonstrated that curcumin could be gradually released to simulate colonic fluid. Notably, the interaction between WPI and OSA-HAS depended on the WPI concentration with the stronger molecular interactions obtained at 35% concentration. CONCLUSION: These results provided important information concerning how to adjust the rheological, anti-digestibility and release properties of WPI-OSA-HAS through altering the electrostatic interactions and hydrophobic interactions of WPI-OSA-HAS. © 2024 Society of Chemical Industry.
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Purpose: The aim of this systematic review was to (1) estimate the prevalence of adhering to the MSE guidelines (at least 2 times/days a week) among adults; and (2) synthesize evidence on the correlates of adhering to the MSE guidelines. Methods: Five electronic databases were searched (March 2022), with a total of 30 observational studies consisting of 2,629,508 participants meeting the eligibility criteria. A meta-analysis was conducted to pool the prevalence of adhering to the MSE guidelines using the results of 21 eligible studies (study aim 1); and data reporting correlates of adhering to the MSE guidelines using 12 eligible studies were synthesized and categorized based on the Socioecological Model Framework (study aim 2). Results: Overall, 22.8 % (95%CI: 18.18 % â 27.77 %) of adults adhered to the MSE guidelines, and 23 potential correlates at five levels were examined. Five variables (i.e., sex, age, education level, socioeconomic status) at the sociodemographic level and two variables (i.e., body mass index, self-rated health) at the physical related level were identified as consistent correlates, but displaying weak to moderate association strengths. Conclusions: Less than a quarter of adults meet the MSE guidelines and multidimensional correlates are associated with the adherence to the guidelines, particularly sociodemographic correlates (e.g., sex, age, and educational level). Findings highlight the need to further promote the importance of engaging in MSE among adults and investing effective interventions that not only provide opportunities for MSE for adults, but also facilitate the development of skills and confidence to engage in MSE.
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BACKGROUND: Hemophagocytic lymphohistiocytosis (HLH) is a potentially fatal systemic inflammation disease in children. The most common cause is Epstein-Barr virus (EBV) infection. MHC class I polypeptide-related sequence B (MICB) is a membrane protein inducibly expressed upon cellular stress, viral infection, or malignant transformation, thus marking these cells for clearance through natural killer group 2 member D-positive lymphocytes. MICB can be released into plasma through several mechanisms, reducing NK cell cytotoxicity. METHODS: We conducted clinical research on HLH patients and cell research in vitro. In the retrospective clinical part, 112 HLH patients (including EBV-HLH group and non-EBV-HLH group), 7 infectious mononucleosis patients, and 7 chronic active EBV infection patients were treated in Beijing Children's Hospital, affiliated with Capital Medical University, from January 2014 to December 2020, were enrolled in this study. Real-time quantitative polymerase chain reaction, standard enzyme-linked immunosorbent assay methods, and lactate dehydrogenase release tests were used to examine the expression of MICB mRNA, the soluble MICB (sMICB) levels, and the activity of NK cells in those patients. In vitro research, MICB overexpression-vector virus, MICB knockdown-vector virus, and empty-vector virus were transfected into two kinds of target cells, such as K562 and MCF7. The level of sMICB and NK cell killing activity between other groups was compared. Finally, we compared NK92 cell killing activity in different concentrations of sMICB. RESULTS: In clinical studies, compared with the non-EBV-HLH group, the EBV-HLH group had lower NK cell killing activity ( P < 0.05). The level of sMICB in the EBV-HLH group was significantly higher than in non-EBV-HLH, infectious mononucleosis, and chronic active EBV infection patients ( P ï¼0.05). A high level of sMICB was associated with poor treatment response and poor prognosis ( P ï¼0. 05). Cellular studies showed that an increased level of membrane MICB could positively correlate with the killing activity of NK92 cells ( P ï¼0. 05), and a high level of sMICB (1250 to 5000pg/ml) could reduce the killing activity of NK92 cells ( P < 0.05). A high level of sMICB (2500pg/ml) could increase the release of cytokines from NK92 cells. CONCLUSION: The expression level of sMICB in EBV-HLH patients increased, and a high level of sMICB at the initial onset indicated a poor treatment response. The killing activity of NK cells in EBV-HLH patients decreased more significantly. The high level of sMICB may inhibit the killing activity but increase the release of cytokines of NK92 cells.
Assuntos
Infecções por Vírus Epstein-Barr , Mononucleose Infecciosa , Linfo-Histiocitose Hemofagocítica , Criança , Humanos , Relevância Clínica , Citocinas/uso terapêutico , Herpesvirus Humano 4/genética , Mononucleose Infecciosa/complicações , Linfo-Histiocitose Hemofagocítica/genética , Estudos RetrospectivosRESUMO
PURPOSE: To assess the relationship between particulate matter 2.5 (PM2.5) levels and the prevalence of excess weight in a representative sample of Spanish young people aged 2â14 years. METHODS: This was an ecological cross-sectional study using data from the 2017 wave of the Encuesta Nacional de Salud Española (ENSE), a nationally representative survey of the Spanish young and adult population. The final sample included 4378 young Spanish people (51.0% boys). The weight (kg) and height (cm) of the study participants were proxy-reported by parents or guardians. Excess weight was determined according to the age- and sex-criteria of the International Obesity Task Force. The PM2.5 level was calculated as the annual monitoring data indicator for 2017 among the different regions in Spain. Logistic regression models were performed to estimate the relationships between PM2.5 and weight. RESULTS: Compared to young people located in regions with low levels of PM2.5, those reporting greater odds for excess weight were found in regions with medium PM2.5 (OR = 1.23; 95% CI, 1.02-1.49) and high PM2.5 (OR = 1.35; 95% CI, 1.11-1.64) after adjusting for several sociodemographic, lifestyle and environmental covariates. CONCLUSIONS: The prevalence of excess weight in young people was positively associated with PM2.5 levels in Spain. This finding supports the hypothesis that air pollution exposure can result in excess weight in the young population, which, in turn, might lead to the development of metabolic disorders. From a socioecological perspective, a practical need to take environmental factors into consideration is important to address unhealthy weight in Spanish young people.
Assuntos
Poluentes Atmosféricos , Poluição do Ar , Adulto , Masculino , Humanos , Adolescente , Feminino , Material Particulado/análise , Estudos Transversais , Poluentes Atmosféricos/toxicidade , Poluentes Atmosféricos/análise , Exposição Ambiental/análise , Poluição do Ar/análise , Aumento de PesoRESUMO
BACKGROUND: In recent years, adolescents have shown a trend of decreasing muscle strength, especially in the upper limbs, and it affects the development of executive functions. However, few studies have been conducted on Tibetan adolescents in high-altitude regions of China. To this end, this study investigated upper limb muscle strength and executive function in Tibetan adolescents in Tibetan regions of China and analyzed the association between them. METHODS: A three-stage stratified whole-group sampling method was used to test and investigate grip strength, executive function, and basic information in 1093 Tibetan adolescents from Tibet, a high-altitude region of China. A chi-square test and one-way ANOVA were used to compare the basic status and executive function of Tibetan adolescents with different muscle strength. Multiple linear regression analysis and logistic regression analysis were used to analyze the correlations that existed between muscle strength and each sub-function of executive function. RESULTS: The differences between the inconsistently and congruent reaction times of Tibetan adolescents with different grip strength levels (