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2.
Pediatr Pulmonol ; 2020 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-33174693

RESUMO

BACKGROUND AND OBJECTIVE: Bronchiolitis obliterans (BO) is a rare but serious condition. The natural history and outcomes remain poorly understood. In this clinical review, we aimed to describe the clinical characteristics and outcomes of children diagnosed with BO in Hong Kong (HK). METHODS: This was a retrospective study of pediatric patients with BO under the care of six respiratory units in HK from January 1996 to December 2015. Information was retrieved from medical records. RESULTS: Fifty-six patients were included with a male predominance (67.9%). The median age at diagnosis was 1.98 years (interquartile range [IQR]: 0.84-4.99 years). Postinfectious BO (PIBO) was the commonest cause (64.3%) followed by posthematopoietic stem-cell transplant (21.4%). Adenovirus (63.2%) was the commonest causative pathogen among PIBO. The median follow-up duration was 9.7 years (IQR: 2.9-14.3 years). Twenty-five patients (44.6%) could achieve symptom-free recovery at the time of follow-up. Five (8.9%) and three (5.4%) were oxygen or ventilator dependent, respectively. There were two deaths, both had posttransplant BO. Patients who developed BO after transplant had significantly worse lung function than those with PIBO. There were no risk factors significantly associated with worse clinical outcomes (oxygen/ventilator dependence or death) by logistic regression. Among patients with PIBO, coinfection at presentation was significantly associated with persistent symptoms at follow-up (p = .028). CONCLUSIONS: The most common cause of childhood BO in HK is postinfectious and coinfection at presentation was associated with persistent symptoms at follow-up. Further studies are needed to better elucidate disease progression, treatment options and long term outcomes.

3.
Sleep Med ; 76: 48-54, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-33091726

RESUMO

OBJECTIVES: To evaluate sleep duration in a representative sample of preschoolers and examine the relationships between screen time and use of different electronic media devices with sleep duration and social jetlag. METHODS: 2903 preschoolers were included. Parent-completed questionnaire provided information on socioeconomic status, electronic media use of the children and sleep patterns of both parents and children. Preschoolers were divided according to whether they met the international screen time recommendations for their age. Comparisons between the two groups in various sleep measures and effects of different devices on sleep were evaluated. RESULTS: 40% of preschoolers in our cohort did not achieve the recommended sleep duration. Subjects who adhered to the screen time recommendations were from families of higher socioeconomic status, had longer sleep duration and better sleep habits. Each hour increase on portable electronic device use was associated with 11 (95%CI: -15 to -6) and 6 (95%CI: -10 to -2) minutes less of average daily sleep duration in boys and girls, respectively. Every additional hour of non-portable electronic devices use was associated with 3 min shift in social jetlag in boys. Presence of electronic devices in bedroom and their use at bedtime increased risk of social jetlag in boys with an OR of 1.40 (95%CI: 1.01 to 1.92) and 1.39 (95%CI: 1.00 to 1.95) respectively. CONCLUSION: A significant proportion of preschoolers does not obtain the recommended amount of sleep. Screen time in preschoolers affects not only sleep duration but also leads to circadian discrepancy.

4.
Biochim Biophys Acta Mol Basis Dis ; 1866(10): 165887, 2020 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-32599141

RESUMO

Intermediary metabolism is traditionally viewed as the large, highly integrated network of reactions that provides cells with metabolic energy, reducing power and biosynthetic intermediates. The elucidation of its major pathways and molecular mechanisms of energy transduction occupied some of the brightest scientific minds for almost two centuries. When these goals were achieved, a sense that intermediary metabolism was mostly a solved problem pervaded the broader biochemical community, and the field lost its vitality. However, intermediary metabolism has recently been re-energized by several paradigm-shifting discoveries that challenged its perception as a self-contained system and re-positioned it at the crossroads of all aspects of cell function, from cell growth, proliferation and death to epigenetics and immunity. Emphasis is now increasingly placed on the involvement of metabolic dysfunction in human disease. In this review, we will navigate from the dawn of intermediary metabolism research to present day work on this ever-expanding field.

5.
Biochim Biophys Acta Mol Basis Dis ; 1866(10): 165841, 2020 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-32439610

RESUMO

Metabolic pathways leading to the synthesis, uptake, and usage of the nonessential amino acid serine are frequently amplified in cancer. Serine encounters diverse fates in cancer cells, including being charged onto tRNAs for protein synthesis, providing head groups for sphingolipid and phospholipid synthesis, and serving as a precursor for cellular glycine and one-carbon units, which are necessary for nucleotide synthesis and methionine cycle reloading. This review will focus on the participation of serine and glycine in the mitochondrial one-carbon (SGOC) pathway during cancer progression, with an emphasis on the genetic and epigenetic determinants that drive SGOC gene expression. We will discuss recently elucidated roles for SGOC metabolism in nucleotide synthesis, redox balance, mitochondrial function, and epigenetic modifications. Finally, therapeutic considerations for targeting SGOC metabolism in the clinic will be discussed.

6.
BMC Pediatr ; 20(1): 115, 2020 03 12.
Artigo em Inglês | MEDLINE | ID: mdl-32164622

RESUMO

BACKGROUND: Respiratory infections are one of three leading causes of childhood mortality, and worldwide increase and recent plateau in childhood asthma has been reported. However, data on trends of respiratory diseases over long period of time is limited. This study aimed to determine the trends of respiratory disease outpatient visits (ROVs) and diagnoses (RODs) in one of the largest children's teaching hospitals in China between 2009 and 2018. METHODS: A retrospective study based on routine administrative data was designed and implemented according to the RECORD statement. Demographic details and diagnoses of the outpatients < 18 years visiting the respiratory department of the hospital were extracted from the Hospital Information System. Age- and gender-specific trends were illustrated by calculating average annual growth rate (AAGR) for ROVs and comparing change of proportion for different RODs over time. RESULTS: There were 698,054 ROVs from 285,574 children (40.4% female). AAGR of ROVs was 15.2%. Children aged 4 to < 7 years had a faster increase than other age groups. Bronchitis (27.6%), pneumonia (18.5%), pneumonia affecting other systems (18.4%), asthma and status asthmaticus (10.7%), and vasomotor and allergic rhinitis (9.2%) accounted for 84.4% of all RODs. The proportion of bronchitis decreased across years, with the concomitant increasing trend in the proportion of pneumonia. Age-specific trend in diagnoses showed greater proportion of asthma in all visits for the children aged 7 to < 18 years than younger children. Gender-specific trend in diagnoses showed the proportion of asthma was greater for males but the AAGR was greater for females. CONCLUSION: The persistent upward trend in ROVs was observed among children at different ages and a gender difference was also seen. In contrast to what has been reported, burden of asthma and allergies diseases continues to increase locally.

7.
Cell Death Dis ; 11(2): 102, 2020 02 06.
Artigo em Inglês | MEDLINE | ID: mdl-32029721

RESUMO

Despite the fact that Otto H. Warburg discovered the Warburg effect almost one hundred years ago, why cancer cells waste most of the glucose carbon as lactate remains an enigma. Warburg proposed a connection between the Warburg effect and cell dedifferentiation. Hypoxia is a common tumor microenvironmental stress that induces the Warburg effect and blocks tumor cell differentiation. The underlying mechanism by which this occurs is poorly understood, and no effective therapeutic strategy has been developed to overcome this resistance to differentiation. Using a neuroblastoma differentiation model, we discovered that hypoxia repressed cell differentiation through reducing cellular acetyl-CoA levels, leading to reduction of global histone acetylation and chromatin accessibility. The metabolic switch triggering this global histone hypoacetylation was the induction of pyruvate dehydrogenase kinases (PDK1 and PDK3). Inhibition of PDKs using dichloroacetate (DCA) restored acetyl-CoA generation and histone acetylation under hypoxia. Knocking down PDK1 induced neuroblastoma cell differentiation, highlighting the critical role of PDK1 in cell fate control. Importantly, acetate or glycerol triacetate (GTA) supplementation restored differentiation markers expression and neuron differentiation under hypoxia. Moreover, ATAC-Seq analysis demonstrated that hypoxia treatment significantly reduced chromatin accessibility at RAR/RXR binding sites, which can be restored by acetate supplementation. In addition, hypoxia-induced histone hypermethylation by increasing 2-hydroxyglutarate (2HG) and reducing α-ketoglutarate (αKG). αKG supplementation reduced histone hypermethylation upon hypoxia, but did not restore histone acetylation or differentiation markers expression. Together, these findings suggest that diverting pyruvate flux away from acetyl-CoA generation to lactate production is the key mechanism that Warburg effect drives dedifferentiation and tumorigenesis. We propose that combining differentiation therapy with acetate/GTA supplementation might represent an effective therapy against neuroblastoma.

8.
Cancer Lett ; 476: 97-105, 2020 04 28.
Artigo em Inglês | MEDLINE | ID: mdl-32032680

RESUMO

Upregulation of serine biosynthesis pathway activity is an increasingly apparent feature of many cancers. Most notably, the first rate-limiting enzyme of the pathway, phosphoglycerate dehydrogenase (PHGDH), is genomically amplified in some melanomas and breast cancers and can be transcriptionally regulated by various tumor suppressors and oncogenes. Yet emerging evidence suggests that serine-in particular, serine biosynthetic pathway activity-may promote cancer in ways beyond providing the building blocks to support cell proliferation. Here, we summarize how mammalian cells tightly control serine synthesis before discussing alternate ways in which increased serine synthetic flux through PHGDH may benefit cancer cells, such as maintenance of TCA cycle flux through alpha-ketoglutarate (αKG) and modulation of cellular redox balance. We will also provide an overview of the current landscape of therapeutics targeting serine synthesis and offer a perspective on future strategies.

9.
Mol Cancer Res ; 18(4): 599-611, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31941752

RESUMO

Breast cancer is the most common cancer among American women and a major cause of mortality. To identify metabolic pathways as potential targets to treat metastatic breast cancer, we performed metabolomics profiling on the breast cancer cell line MDA-MB-231 and its tissue-tropic metastatic subclones. Here, we report that these subclones with increased metastatic potential display an altered metabolic profile compared with the parental population. In particular, the mitochondrial serine and one-carbon (1C) unit pathway is upregulated in metastatic subclones. Mechanistically, the mitochondrial serine and 1C unit pathway drives the faster proliferation of subclones through enhanced de novo purine biosynthesis. Inhibition of the first rate-limiting enzyme of the mitochondrial serine and 1C unit pathway, serine hydroxymethyltransferase (SHMT2), potently suppresses proliferation of metastatic subclones in culture and impairs growth of lung metastatic subclones at both primary and metastatic sites in mice. Some human breast cancers exhibit a significant association between the expression of genes in the mitochondrial serine and 1C unit pathway with disease outcome and higher expression of SHMT2 in metastatic tumor tissue compared with primary tumors. In addition to breast cancer, a few other cancer types, such as adrenocortical carcinoma and kidney chromophobe cell carcinoma, also display increased SHMT2 expression during disease progression. Together, these results suggest that mitochondrial serine and 1C unit metabolism plays an important role in promoting cancer progression, particularly in late-stage cancer. IMPLICATIONS: This study identifies mitochondrial serine and 1C unit metabolism as an important pathway during the progression of a subset of human breast cancers.

10.
Sci Rep ; 10(1): 341, 2020 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-31941940

RESUMO

We aimed to determine if prematurity and lower birth weight are associated with poorer lung function in a non-western developed setting with less marked confounding by socioeconomic position. Using multivariable linear regression in Hong Kong's "Children of 1997" birth cohort, adjusted associations of prematurity and birth weight with forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), and forced expiratory flow at 25-75% of the pulmonary volume (FEF25-75%) at ~17.5 years were assessed. Associations for birth weight were stronger in boys for FEV1 (boys: 0.31 L, 95% confidence interval (CI) 0.24 to 0.38, girls: 0.18 L, 95% CI 0.12 to 0.25), FVC (boys: 0.36 L, 95% CI 0.27 to 0.44, girls: 0.22 L, 95% CI 0.15 to 0.28) and FEF25-75% (boys: 0.35 L, 95% CI 0.21 to 0.49, girls: 0.22 L, 95% CI 0.09 to 0.34) adjusted for age, socioeconomic position and infant and maternal characteristics. Similarly adjusted, preterm birth (compared to full-term birth) was associated with lower FEV1/FVC and FEF25-75%. Thus, associations of lower birth weight, especially in boys, and prematurity with poorer lung function at 17.5 years were found. Identifying underlying mechanism might contribute to the improvement of pulmonary health and the prevention of adult respiratory illness.


Assuntos
Peso ao Nascer , Pulmão/fisiologia , Nascimento Prematuro , Feminino , Seguimentos , Volume Expiratório Forçado , Humanos , Recém-Nascido , Masculino , Testes de Função Respiratória
11.
J Clin Sleep Med ; 15(11): 1561-1570, 2019 11 15.
Artigo em Inglês | MEDLINE | ID: mdl-31739845

RESUMO

STUDY OBJECTIVES: Previous studies suggest the presence of familial aggregation of obstructive sleep apnea (OSA) in adults. However, similar data on childhood OSA are limited. This family study aimed to investigate the heritability and familial aggregation of childhood OSA and to examine whether significant differences existed between patients of normal weight and overweight. METHODS: Children aged 6 to 18 years were recruited as probands either from attendants to sleep clinic (with habitual snoring) or the community (without habitual snoring). Parents and siblings of the probands were also invited to participate. All participants underwent nocturnal sleep study. RESULTS: A total of 229 probands took part, of whom 33 had moderate to severe OSA, 70 had mild disease, and 126 had no OSA. A total of 412 relatives were also recruited. Although the overall heritability of obstructive apnea-hypopnea index (OAHI) was not significant (h² ± SE = 0.03 ± 0.09, P = .37), it was significant in overweight individuals on subgroup analysis (h² ± SE = 0.43 ± 0.24, P = .032). Significant interaction effect of overweight was demonstrated in both heritability and familial aggregation analyses. Bivariate genetic analysis found that the genetic correlation between OAHI and body mass index in overweight individuals (ρg ± SE = 0.63 ± 0.18) was significantly different from both 0 (P = .005) and 1 (P = .025). CONCLUSIONS: The differential results of heritability and familial aggregation of OSA in normal weight and overweight subgroups substantiated the recommendation of separating childhood OSA into normal weight and overweight subtypes. In the overweight subgroup, there may be obesity-independent components involved in the genetic variance of OAHI, although a significant proportion of the genetic variance is shared with obesity.

12.
Obesity (Silver Spring) ; 27(6): 1013-1022, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31067017

RESUMO

OBJECTIVE: This study used two complementary designs, an observational and a Mendelian randomization (MR) study, to assess whether sleep duration causes adiposity in children and adults. METHODS: In Hong Kong's "Children of 1997" birth cohort, the adjusted cross-sectional associations of sleep duration with BMI z score and obesity and overweight were assessed at ~11 years of age. Generalized estimating equations were also used to examine longitudinal associations of sleep duration at ~11 years with annual BMI z score and obesity and overweight at about 11 to 16 years of age. Using MR, this study assessed the association of genetically predicted sleep duration, based on 54 single-nucleotide polymorphisms, applied to genetic studies of adiposity in children (n = 35,668), men (n = 152,893), and women (n = 171,977). RESULTS: Longer sleep was cross-sectionally associated with lower BMI z score at ~11 years of age (-0.13 per category, 95% CI: -0.22 to -0.04) and at about 11 to 16 years of age longitudinally in girls (-0.39, 95% CI: -0.66 to -0.13). Using MR, sleep duration was inversely associated with BMI in children (-0.29 SD per hour, 95% CI: -0.54 to -0.04), but was not clearly associated with BMI in adults, particularly for women. CONCLUSIONS: A small beneficial effect of sleep on BMI in children cannot be ruled out.


Assuntos
Adiposidade/fisiologia , Sono/fisiologia , Adolescente , Adulto , Criança , Estudos Transversais , Feminino , Humanos , Masculino , Análise da Randomização Mendeliana
13.
Chest ; 156(1): 120-130, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-30922948

RESUMO

BACKGROUND: Understanding the natural history of childhood OSA can help to determine disease prognosis and to guide risk stratification and management strategies. METHODS: To evaluate the natural history of childhood OSA and factors associated with spontaneous remission and persistent and incident OSA from childhood to late adolescence/early adulthood, a longitudinal analysis of a prospective community-based cohort was designed. Subjects from a cohort established for an OSA prevalence study were invited to participate in this 10-year follow-up study. RESULTS: Two hundred and forty-three participants (59% male) took part, and their mean age was 9.8 (SD, ± 1.8) and 20.2 (SD, ± 1.9) years at baseline and follow-up, respectively. The mean follow-up duration was 10.4 (SD, ± 1.1) years. Associations between baseline and follow-up log-transformed obstructive apnea-hypopnea index (OAHI) differed by age; a significant positive association was observed only among participants aged 10 years or older at baseline. Overall polysomnographic remission rate (with OAHI < 1 event/h at follow-up) of childhood OSA was 30%, and 69% had an OAHI < 5 events/h at follow-up. Complete remission of OSA was associated with female sex. Incidence of adolescent/adult OSA with an OAHI ≥ 5 events/h at follow-up was 22%. Male sex and higher baseline BMI z score were associated with incident OSA. CONCLUSIONS: A proportion of children with OSA, particularly female children, had complete resolution during transition to late adolescence or early adulthood. Childhood and adolescent OSA are distinct entities, with the latter more likely to persist into adulthood. Obesity and male sex are consistent key risk factors for incident OSA.


Assuntos
Apneia Obstrutiva do Sono/epidemiologia , Apneia Obstrutiva do Sono/fisiopatologia , Adolescente , Fatores Etários , Criança , Feminino , Seguimentos , Humanos , Estudos Longitudinais , Masculino , Obesidade/complicações , Polissonografia , Prognóstico , Estudos Prospectivos , Remissão Espontânea , Medição de Risco , Fatores Sexuais , Adulto Jovem
14.
PLoS One ; 14(3): e0213674, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30861055

RESUMO

OBJECTIVE: To investigate scaling approaches for evaluating the development of peak VO2 and improving the identification of low cardiopulmonary fitness in Southern Chinese children and adolescents. METHODS: Nine hundred and twenty Chinese children and adolescents (8 to 16 years) underwent graded cardiopulmonary exercise test on a treadmill until volitional exhaustion. Peak VO2 was corrected for the effects of body mass by ratio or allometric scaling. Z score equations for predicting peak VO2 were developed. Correlations between scaled peak VO2, z scores, body size and age were tested to examine the effectiveness of the approach. RESULTS: Eight hundred and fifty-two participants (48% male) were included in the analyses. Absolute peak VO2 significantly increased with age in both sexes (both P<0.05), while ratio-scaled peak VO2 increased only in males (P<0.05). Allometrically scaled peak VO2 increased from 11 years in both sexes, plateauing by 12 years in girls and continuing to rise until 15 years in boys. Allometically scaled peak VO2 was not correlated with body mass, but remained correlated with height and age in all but the older girls. Peak VO2 z score was not correlated with body mass, height or age. CONCLUSIONS: Absolute and allometric scaled peak VO2 values are provided for Hong Kong Chinese children and adolescents by age and sex. Peak VO2 z scores improve the evaluation of cardiopulmonary fitness, allowing comparisons across ages and sex and will likely provide a better metric for tracking change over time in children and adolescents, regardless of body size and age.


Assuntos
Aptidão Cardiorrespiratória , Teste de Esforço/normas , Exercício Físico , Consumo de Oxigênio , Adolescente , Fatores Etários , Antropometria , Grupo com Ancestrais do Continente Asiático , Tamanho Corporal , Peso Corporal , Criança , China , Feminino , Hong Kong , Humanos , Masculino , Valores de Referência , Sistema Respiratório
15.
Environ Int ; 123: 444-450, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30622069

RESUMO

BACKGROUND: Early-life air pollution exposure is associated with lung function in children and adolescents. However, whether the association of prenatal and early postnatal exposure to air pollution with lung function continues into adulthood remains unclear. OBJECTIVE: To investigate the associations of early exposure to air pollution with lung function at ~17.5 years in a non-western developed setting with more concentrated air pollutants. METHODS: We examined the associations of exposure to particular matter with an aerodynamic diameter of <10 µm (PM10), nitrogen dioxides (NO2), nitric oxide (NO), sulfur dioxide (SO2) in standard deviations (SD)) at different early life stages with lung function (indicated by forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1) and forced expiratory flow at 25%-75% of the pulmonary volume (FEF25%-75%)) in SD at ~17.5 years, personal history of wheezing and asthma in the population-representative Hong Kong Chinese birth cohort "Children of 1997"(n = 2942). RESULTS: Higher in utero and infancy and toddlerhood NO2 were associated with lower FEV1 (-0.022, 95% confidence interval (CI) -0.029 to -0.015 and - 0.026, 95% CI -0.033 to -0.019), FEV1/FVC (-0.035, 95% CI -0.050 to -0.021 and -0.052, 95% CI -0.066 to -0.038) and FEF25%-75% (-0.031, 95% CI -0.040 to -0.022 and -0.043, 95% CI -0.051 to -0.035). A similar association was observed for NO. Weak associations of NO2 and NO with FVC were observed (-0.011, 95% CI -0.018 to -0.003 and -0.010, 95% CI -0.020 to -0.001). NOx was associated with higher risk of wheezing (1.08, 95% CI 1.03 to 1.14) but not asthma (1.02, 95% CI 0.94 to 1.11). SO2 and PM10 were not clearly associated with lung function, wheezing or asthma. CONCLUSION: Our findings suggest that early exposure to air pollution from NO2 may have long-term effects on lung function, which could affect respiratory health throughout life.


Assuntos
Poluentes Atmosféricos/toxicidade , Poluição do Ar/efeitos adversos , Exposição Ambiental/efeitos adversos , Pulmão/efeitos dos fármacos , Dióxido de Nitrogênio/toxicidade , Adolescente , Grupo com Ancestrais do Continente Asiático , Asma , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Seguimentos , Volume Expiratório Forçado , Hong Kong , Humanos , Lactente , Masculino , Óxido Nítrico/toxicidade , Gravidez , Efeitos Tardios da Exposição Pré-Natal , Testes de Função Respiratória , Dióxido de Enxofre/toxicidade , Capacidade Vital
16.
Pediatr Res ; 85(4): 449-455, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30679794

RESUMO

BACKGROUND: This study aims to study prospectively specific sleep patterns and risk of ADHD after adjusting for potential confounders such as obstructive sleep apnoea (OSA) and methylphenidate use. METHODS: A population-representative sample of 514 Chinese preschool children was recruited when in kindergarten (K3). Parents reported on their socioeconomic status and children's sleep duration. The cohort was reassessed 3 years later when the children were in Grade 3 (P3). Parents reported on children's sleep patterns and ADHD symptoms. Information on OSA diagnosis and methylphenidate use was retrieved from health records. RESULTS: Among the 514 parent-child dyads (mean [SD] age, 5.52 [0.33] years), 411 were reassessed (80.0% retention; 9.35 [0.33] years) at follow-up. There were no significant baseline differences between follow-up and drop-out groups. A gradient relationship was observed between probable ADHD in P3 and sleep duration in K3. The risk of probable ADHD was 15.5 per 100 for children with <8 h of sleep in K3, whereas it was 1.1 per 100 for children with 11-12 h of sleep in K3. The adjusted risk ratio was 14.19 (p = 0.02). CONCLUSIONS: Sleep deprivation in early childhood is associated with higher risk of ADHD in middle childhood.


Assuntos
Transtorno do Deficit de Atenção com Hiperatividade/complicações , Privação do Sono , Criança , Pré-Escolar , China , Feminino , Humanos , Masculino , Estudos Prospectivos , Fatores Socioeconômicos
17.
Am J Respir Crit Care Med ; 196(12): 1591-1598, 2017 12 15.
Artigo em Inglês | MEDLINE | ID: mdl-28759260

RESUMO

RATIONALE: The vast majority of children around the world undergoing adenotonsillectomy for obstructive sleep apnea-hypopnea syndrome (OSA) are not objectively diagnosed by nocturnal polysomnography because of access availability and cost issues. Automated analysis of nocturnal oximetry (nSpO2), which is readily and globally available, could potentially provide a reliable and convenient diagnostic approach for pediatric OSA. METHODS: Deidentified nSpO2 recordings from a total of 4,191 children originating from 13 pediatric sleep laboratories around the world were prospectively evaluated after developing and validating an automated neural network algorithm using an initial set of single-channel nSpO2 recordings from 589 patients referred for suspected OSA. MEASUREMENTS AND MAIN RESULTS: The automatically estimated apnea-hypopnea index (AHI) showed high agreement with AHI from conventional polysomnography (intraclass correlation coefficient, 0.785) when tested in 3,602 additional subjects. Further assessment on the widely used AHI cutoff points of 1, 5, and 10 events/h revealed an incremental diagnostic ability (75.2, 81.7, and 90.2% accuracy; 0.788, 0.854, and 0.913 area under the receiver operating characteristic curve, respectively). CONCLUSIONS: Neural network-based automated analyses of nSpO2 recordings provide accurate identification of OSA severity among habitually snoring children with a high pretest probability of OSA. Thus, nocturnal oximetry may enable a simple and effective diagnostic alternative to nocturnal polysomnography, leading to more timely interventions and potentially improved outcomes.


Assuntos
Oximetria/métodos , Apneia Obstrutiva do Sono/diagnóstico , Ronco/diagnóstico , Adolescente , Algoritmos , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Estudos Prospectivos , Reprodutibilidade dos Testes , Índice de Gravidade de Doença , Apneia Obstrutiva do Sono/complicações , Ronco/complicações , Inquéritos e Questionários
18.
Influenza Other Respir Viruses ; 11(4): 319-327, 2017 07.
Artigo em Inglês | MEDLINE | ID: mdl-28444974

RESUMO

BACKGROUND: Influenza imposes substantial healthcare burden in children, which can be prevented by vaccination. Influenza vaccination coverage varies widely among childhood populations worldwide, which has significant impact on herd immunity and usefulness of influenza vaccine. However, there are limited real-life data on influenza vaccine effectiveness (VE) in children. OBJECTIVE: This prospective study aimed to investigate clinical spectrum of childhood influenza and VE in preventing influenza in Hong Kong children. METHODS: A total of 623 children were recruited from 15 kindergartens and primary schools. Parents completed a questionnaire on subjects' health and influenza vaccination history. Flocked nasopharyngeal swabs (FNPSs) were collected in biweekly school visits during 2014-2015 influenza seasons. Influenza A and B viruses were detected and typed by molecular assays. RESULTS: A total of 2633 FNPS samples were collected, with two or more samples being obtained from 607 (97.4%) of subjects. Thirty-six (11.2%) subjects had influenza A or B in 2014, whereas all 19 (6.3%) subjects identified in 2015 had influenza A. Ninety-nine subjects reported influenza-like illness (ILI), and nine illness visits were arranged. Influenza vaccination was protective against ILI but not mild laboratory-confirmed influenza by surveillance. Moderate overall influenza VE of 42%-52% was observed for ILI, and subgroup analyses showed much higher VE for both ILI (70.9% vs 34.6%) and mild laboratory-confirmed influenza (44.0% vs -6.2%) in school-age children than preschoolers who were vaccinated within 12 months. CONCLUSIONS: Mild laboratory-confirmed influenza infection is common in children during influenza seasons. Influenza vaccination is effective against ILI but not mild infection identified by surveillance.


Assuntos
Vacinas contra Influenza/administração & dosagem , Influenza Humana/prevenção & controle , Criança , Pré-Escolar , Feminino , Hong Kong/epidemiologia , Humanos , Vírus da Influenza A/classificação , Vírus da Influenza A/genética , Vírus da Influenza A/imunologia , Vírus da Influenza A/isolamento & purificação , Vírus da Influenza B/genética , Vírus da Influenza B/isolamento & purificação , Vírus da Influenza B/fisiologia , Vacinas contra Influenza/imunologia , Influenza Humana/epidemiologia , Influenza Humana/virologia , Masculino , Vigilância da População , Estudos Prospectivos , Instituições Acadêmicas , Estações do Ano
19.
Mol Genet Genomic Med ; 5(1): 40-49, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-28116329

RESUMO

BACKGROUND: Cystic fibrosis (CF) is a rare condition in Asians. Since 1985, only about 30 Chinese patients have been reported with molecular confirmation. METHOD: Using our in-house next-generation sequencing (NGS) pipeline for childhood bronchiectasis, we identified disease-causing CFTR mutations in CF patients in Hong Kong. After identifying p.I1023R in multiple patients, haplotype analysis was performed with genome-wide microarray to ascertain the likelihood of this being a founder mutation. We also assessed the processing and gating activity of the mutant protein by Western hybridization and patch-clamp test. RESULTS: Molecular diagnoses were confirmed in four patients, three of whom shared a missense mutation: CFTR:c.3068T>G:p.I1023R. The results suggested that p.I1023R is a founder mutation in southern Han Chinese. In addition, the processing and gating activity of the mutant protein was assessed by gel electrophoresis and a patch-clamp test. The mutant protein exhibited trafficking defects, suggesting that the dysfunction is caused by reduced cell surface expression of the fully glycosylated proteins. CONCLUSION: Together with other previously reported mutations, the specific founder mutation presented herein suggests a unique CFTR mutation spectrum in the southern Chinese populations, and this finding has vital implications for improving molecular testing and mutation-specific treatments for Chinese patients with CF.

20.
J Paediatr Child Health ; 52(4): 385-90, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-27145500

RESUMO

AIM: The aim of this study is to determine the association between waist circumference (WC) and childhood-masked hypertension. METHODS: A territory-wide, school-based cohort of 1385 Hong Kong students (672 boys and 713 girls) aged 8-17 years was analysed. The ambulatory blood pressure-monitoring assessment was performed using validated oscillometric recorders (A&D TM-2430 (A&D Inc., Tokyo, Japan)) following American Heart Association's recommendations. Subjects were considered normotensive if their casual blood pressure, 24-h daytime and night-time average systolic blood pressure and diastolic blood pressure (DBP) were <95th percentile. If one or more of the ambulatory blood pressure parameters was ≥95th percentile, subjects would be considered suffering from masked hypertension (MH). Subjects who had three successive casual blood pressure measurements above the 95th percentile were excluded. RESULTS: By body mass index, 148 (10.7%) subjects were obese, 182 (13.1%) overweight and 359 (25.9%) having larger WC (≥85th percentiles). MH was diagnosed in 217 subjects (15.7%). Subjects with larger WC or obesity were significantly associated with higher 24-h daytime and night-time systolic blood pressure (≥95th percentile) (odds ratios from 1.84 to 2.09 and from 2.07 to 3.54 for larger WC and obese respectively, all P < 0.05) as well as 24-h DBP for larger WC (odds ratio = 2, P = 0.015) than normal subjects adjusted by sex, age and height. CONCLUSION: Waist circumference and body mass index are independent risk factors of childhood and adolescent MH. WC appears a significant associated factor of elevated 24-h DBP in children aged 8-17 years.


Assuntos
Índice de Massa Corporal , Hipertensão Mascarada/diagnóstico , Hipertensão Mascarada/epidemiologia , Circunferência da Cintura/fisiologia , Adolescente , Distribuição por Idade , Antropometria , Determinação da Pressão Arterial , Monitorização Ambulatorial da Pressão Arterial , Criança , Estudos de Coortes , Intervalos de Confiança , Estudos Transversais , Feminino , Seguimentos , Hong Kong/epidemiologia , Humanos , Incidência , Masculino , Razão de Chances , Valor Preditivo dos Testes , Medição de Risco , Índice de Gravidade de Doença , Distribuição por Sexo
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