In the past 40 years,advances in neonatal intensive care unit(NICU)technology have enabled premature infants with lower birth weight and younger gestational age to survive.But with it comes an increase in the incidenc...In the past 40 years,advances in neonatal intensive care unit(NICU)technology have enabled premature infants with lower birth weight and younger gestational age to survive.But with it comes an increase in the incidence of long-term respiratory dysfunction,mainly in the form of bronchopulmonary dysplasia(BPD).Preventing lung injury is crucial for preventing BPD and improving the long-term prognosis of premature infants.Therefore,how to avoid ventilator-associated lung injury has become a focus of clinical and scientific research in premature infants in recent years.This article will elaborate on the susceptibility and pathophysiology of premature infant lung injury,ventilation strategies for preventing lung injury,and new advances in neonatal respiratory support.展开更多
We aim to provide an up-to-date summary of infantile hepatic hemangioma(IHH) and its misnomers and to dialectically present the differential diagnosis of these rare entities of the liver.Eligible peer-reviewed article...We aim to provide an up-to-date summary of infantile hepatic hemangioma(IHH) and its misnomers and to dialectically present the differential diagnosis of these rare entities of the liver.Eligible peer-reviewed articles on hepatic infantile hemangiomas,published between 2000 and 2015,were reviewed for this study.IHH is the most common hepatic vascular tumor in children.Once a liver mass is identified in an infant,the differential diagnosis ranges from vascular malformations to benign and malignant tumors including mesenchymal hamartoma,hepatoblastoma,metastatic neuroblastoma,so careful physical examination,imaging studies,and,if indicated,tumor markers and biopsy,are of pivotal importance to ascertain the correct diagnosis.Despite the benign nature of IHHs,some of these lesions may demand medical and/or surgical intervention,especially for multiple and diffuse IHH.Complications can include hepatomegaly,hypothyroidism and cardiac failure.Therefore,a close follow-up is required until complete involution of the lesions.We propose an algorithm to guide the physicians towards the proper management of hepatic lesions.展开更多
This article provides a comprehensive overview of key issues related to pediatric drug development and rational dosing guidance in pediatrics with an emphasis on how pharmacometrics can improve the efficiency and prod...This article provides a comprehensive overview of key issues related to pediatric drug development and rational dosing guidance in pediatrics with an emphasis on how pharmacometrics can improve the efficiency and productivity of pediatric trials.The pharmacokinetics(PK)and pharmacodynamics(PD)of drugs are often different between adult and pediatric populations which necessitate specific studies in children.The aims of this review are to discuss a number of recent methodological developments of modeling and simulation that facilitate the evaluation of drugs in pediatrics.Specific focus has been placed on addressing the key issues of PK/PD scaling,sparse sampling,colinearity,covariate evaluation,dose optimization for trial design and label,modeling strategies and validation approaches.The features and potential advantages of Bayesian hierarchical model,physiology-based PK models,and K-PD models are also presented.展开更多
Background and purpose Rapid genotyping is useful for guiding early antiplatelet therapy in patients with high-risk nondisabling ischaemic cerebrovascular events(HR-NICE).Conventional genetic testing methods used in C...Background and purpose Rapid genotyping is useful for guiding early antiplatelet therapy in patients with high-risk nondisabling ischaemic cerebrovascular events(HR-NICE).Conventional genetic testing methods used in CYP2C19 genotype-guided antiplatelet therapy for patients with HR-NICE did not satisfy the needs of the Clopidogrel in High-Risk Patients with Acute Nondisabling Cerebrovascular Events(CHANCE)-2 trial.Therefore,we developed the rapid-genotyping GMEX(point-of care)system to meet the needs of the CHANCE-2 trial.Methods Healthy individuals and patients with history of cardiovascular diseases(n=408)were enrolled from six centres of the CHANCE-2 trial.We compared the laboratory-based genomic test results with Sanger sequencing test results for accuracy verification.Next,we demonstrated the accuracy,timeliness and clinical operability of the GMEX system compared with laboratory-based technology(YZY Kit)to verify whether the GMEX system satisfies the needs of the CHANCE-2 trial.Results Genotypes reported by the GMEX system showed 100%agreement with those determined by using the YZY Kit and Sanger sequencing for all three CYP2C19 alleles(*2,*3 and*17)tested.The average result’s turnaround times for the GMEX and YZY Kit methods were 85.0(IQR:85.0-86.0)and 1630.0(IQR:354.0-7594.0)min(p<0.001),respectively.Conclusions Our data suggest that the GMEX system is a reliable and feasible point-of care system for rapid CYP2C19 genotyping for the CHANCE-2 trial or related clinical and research applications.展开更多
Cancer remains a major cause of human mortality. The greatest barrier to cure is resistance to conventional medi- cal treatments. Therapy resistance arises through clonal evolution driven by ge- nomic instability, fos...Cancer remains a major cause of human mortality. The greatest barrier to cure is resistance to conventional medi- cal treatments. Therapy resistance arises through clonal evolution driven by ge- nomic instability, fostered by selection as therapy-sensitive ceils are eradicated. Such resistance has been attributed to al- terations in numerous cellular pathways, yet many ultimately impact the process ofmitochondrial apoptosis. The critical gatekeepers for mitochondrial apoptosis initiation are the Bcl2-homology （BH） proteins, whose interactions integrate the varied stressors a cell encounters and provide a live-or-die decision （reviewed in [1]）. As such, BH proteins are the frequent target of alterations in cancer cells during oncogenesis and tumor progression [2].展开更多
Chronic obstructive pulmonary disease(COPD)is a leading cause of disability and death of adults in the USA and worldwide.While environmental factors such as smoking and air pollution are major contributors to COPD,ped...Chronic obstructive pulmonary disease(COPD)is a leading cause of disability and death of adults in the USA and worldwide.While environmental factors such as smoking and air pollution are major contributors to COPD,pediatric respiratory disease and more specifically early childhood wheezing are frequent predisposing factors.It is therefore possible that aggressive prevention and treatment of childhood respiratory illness may modify adult COPD risk.This article reviews some of the physiological factors that may explain the pediatric origins of childhood lung disease.One such factor is the"tracking"of normal lung function which occurs with growth.The maximal expiratory flow volume(MEFV)curve is an ideally suited tool to monitor tracking of airway function over the lifespan,as its relative effort independence makes it highly reliable.Study of the MEFV curve has demonstrated that individuals with similar lung volumes can have large differences in maximal flows,reflecting a disconnection between airway and lung growth("dysanapsis").Less than average airway size due to dysanaptic airway growth or airway remodeling may be independent risk factors for the development of COPD and the asthma/COPD overlap syndrome in adult life.There are intriguing early data suggesting that perhaps at least some of this risk is modifiable by improving asthma control with inhaled corticosteroids and minimizing asthma exacerbations.展开更多
Objective:Because children with congenital hyperinsulinism(HI) caused by recessive loss of function mutations in the adenosine triphosphate (ATP)-dependent potassium channel(KATP-HI) are not leucine sensitive,we evalu...Objective:Because children with congenital hyperinsulinism(HI) caused by recessive loss of function mutations in the adenosine triphosphate (ATP)-dependent potassium channel(KATP-HI) are not leucine sensitive,we evaluated for protein induced hypoglycemia with oral protein tolerance tests. Study design:Blood glucose and insulin concentrations were measure devery 15 minutes for 3 hours after an oral protein loadin children with KATP-HI (n=11) and compared with those of children with glutamate dehydrogenase HI (n=12) and control subjects (n=12). Results:Similar to children with glutamate dehydrogenase HI,patients with KATP-HI displayed protein-induced hypoglycemia (10/11)with blood glucose concentrations declining by 17 to 69 mg/dL. In contrast,oral proteinhad little effect on blood glucose concentrations in control subjects.Conclusions:Protein induced hypoglycemia is a feature of KATP-HI,despite the absence of leucine sensitivity. The results indicate that amino acids can stimulate insulin secretionvia a glutamate dehydrogenase and KATP channel-independent pathway.展开更多
Dear Sir,I n their article, ＂A comparison between monocanalicular and pushed monocanalicular silicone intubation in the treatment of congenital nasolacrimal duct obstruction＂, Andalib et al present the results of a...Dear Sir,I n their article, ＂A comparison between monocanalicular and pushed monocanalicular silicone intubation in the treatment of congenital nasolacrimal duct obstruction＂, Andalib et al present the results of a prospective study on congenital nasolacrimal duct obstruction treated either with a Monoka stent （using a Crawford hook for nasal retrieval） or a Masterka pushed technique for insertion of the Masterka stent. The success rates were respectively 90% and 50%.展开更多
We present a case report of a boy with biliary atresia who,after hepatoportoenterostomy performed on day 21 of life, had immediate resolution of cholestasis and remained anicteric until 3.5 months of age. He then abru...We present a case report of a boy with biliary atresia who,after hepatoportoenterostomy performed on day 21 of life, had immediate resolution of cholestasis and remained anicteric until 3.5 months of age. He then abruptly developed acholic stools.Nuclear medicine imaging study showed no excretion. Broadspectrum antibiotics and corticosteroids were administered but did not lead to clinical improvement; a surgical revision of the original anastomosis was undertaken at 4 months of age. At 14 months of age, the child is anicteric and growing well. In this case, successful revision of hepatoportoenterostomy averted the need for liver transplantation.展开更多
Objective:To evaluate risk factors for recurrent thrombosis in pediatric patients. Study design:This prospective observational cohort study enrolled 120 patients with acute venous thromboembolism from January 2003 to ...Objective:To evaluate risk factors for recurrent thrombosis in pediatric patients. Study design:This prospective observational cohort study enrolled 120 patients with acute venous thromboembolism from January 2003 to April 2005. Datacollection included medical and family history,radiologic and laboratory studies,therapy,and follow-up. Results:The overall prevalence of recurrent thrombosis in our cohort was 19/120(15.8%). Patients with recurrence were older,with a median age of 14.8 years (range 2 weeks-23.6 years),compared with 10.1years (range newborn 23.4 years) in patients without recurrence(P = 0.03). Six of the 19 patients with recurrent thrombosis had cystic fibrosis (CF),compared with 0/101without recurrence (P< 0.001). Five of these 6 patients were colonized with Burkholderia cepacia in their sputum. Central venous catheters were associated with most,but not all,of the thromboses in patients with CF. Conclusions:In this study,patients with CF had a high risk of recurrent venous thrombosis,as well as a high prevalence of colonization with B cepacia. The cause of this risk has not been defined. This observation may have important implications for thromboprophylaxis,particularly in the setting of central venous catheters.展开更多
Increased resting energy expenditure (REE) is a possible explanation for the negative energy balance seen in children with Alagille syndrome (AGS).We evaluated 16 subjects with AGS and 37 healthy controls and did not ...Increased resting energy expenditure (REE) is a possible explanation for the negative energy balance seen in children with Alagille syndrome (AGS).We evaluated 16 subjects with AGS and 37 healthy controls and did not find a significant difference in REE (101%±12%,105%±13%,respectively).展开更多
Background:To describe the sleep patterns of children below 36 months in Hong Kong,and evaluate the associations between parental behaviors and childhood sleep/wake patterns.Methods:Parents of 1049 infants and toddler...Background:To describe the sleep patterns of children below 36 months in Hong Kong,and evaluate the associations between parental behaviors and childhood sleep/wake patterns.Methods:Parents of 1049 infants and toddlers completed an internet-based expanded version of the Brief Infant Sleep Questionnaire.Results:Total sleep duration (P<0.001),frequency (P<0.001) and duration (P<0.001) of nocturnal awakenings decreased with age,whereas the longest sleep duration (P<0.001) and nocturnal sleep duration (P<0.001) increased with age.Children who room-or bed-shared with parents had later bedtimes (P<0.001),but similar sleep duration compared with those who had a separate sleep location.Falling asleep independently was associated with longer nocturnal sleep duration (P<0.001) and less sleep awakenings (P<0.001).Full-time employment of parents was associated with shorter total sleep duration of children (P<0.001).Although breastfeeding was associated with more nocturnal awakenings (P<0.001),no association was detected between breastfeeding and shorter sleep duration in children.Conclusions:As infants and toddlers develop,their sleep consolidates.Falling asleep independently was associated with longer nocturnal sleep duration and fewer sleep awakenings,whereas sleep location was not.This is an important finding,especially for families with limited living space where parent/ child room-or bed-sharing cannot be avoided.展开更多
DNA sensing and timely activation of interferon(IFN)-mediated innate immunity are crucial for the defense against DNA virus infections and the clearance of abnormal cells.However,overactivation of immune responses may...DNA sensing and timely activation of interferon(IFN)-mediated innate immunity are crucial for the defense against DNA virus infections and the clearance of abnormal cells.However,overactivation of immune responses may lead to tissue damage and autoimmune diseases;therefore,these processes must be intricately regulated.STING is the key adaptor protein,which is activated by cyclic GMP-AMP,the second messenger derived from cGAS-mediated DNA sensing.Here,we report that CCDC50,a newly identified autophagy receptor,tunes STING-directed type I IFN signaling activity by delivering K63-polyubiquitinated STING to autolysosomes for degradation.Knockout of CCDC50 significantly increases herpes simplex virus 1(HSV-1)-or DNA ligand-induced production of type I IFN and proinflammatory cytokines.Ccdc50-deficient mice show increased production of IFN,decreased viral replication,reduced cell infiltration,and improved survival rates compared with their wild-type littermates when challenged with HSV-1.Remarkably,the expression of CCDC50 is downregulated in systemic lupus erythematosus(SLE),a chronic autoimmune disease.CCDC50 levels are negatively correlated with IFN signaling pathway activation and disease severity in human SLE patients.CCDC50 deficiency potentiates the cGAS-STING-mediated immune response triggered by SLE serum.Thus,our findings reveal the critical role of CCDC50 in the immune regulation of viral infections and autoimmune diseases and provide insights into the therapeutic implications of CCDC50 manipulation.展开更多
Preschool children with asthma present a challenge in lung function testing, as they cannot readily cooperate with spirometry. The forced oscillation technique (FOT) measures passive pressures and flows delivered by a...Preschool children with asthma present a challenge in lung function testing, as they cannot readily cooperate with spirometry. The forced oscillation technique (FOT) measures passive pressures and flows delivered by a loudspeaker to a facemask, at frequencies much higher than those occurring physiologically. This in turn allows for rapid collection of data from a spontaneously breathing child in a timespan of seconds. However, at very rapid oscillatory flow rates, the mechanical properties opposing flows into and out of the respiratory system (collectively termed the respiratory system impedance, and comprised of elastic, resistive and inertial components) are very different from at normal breathing frequencies, with elastic properties being less important and inertial properties being more important. An understanding of how the respiratory system behaves at high frequencies is essential to understanding the physiological basis of this technique. This article presents a way to understand these oscillatory mechanics of the respiratory system. It then describes studies of the FOT in normal preschool children and in children with asthma. The technique can also measure the separate contributions of the central and peripheral airways, as well as assess for changes after bronchodilator administration. The FOT holds promise for the objective measurement of lung function in children who are too young to reliably perform spirometry.展开更多
Introduction:Impulse oscillometry(IOS)employs high frequency sinusoidal or impulse pressure and flow waveforms to interrogate the mechanical properties of the respiratory system.It has special applications to preschoo...Introduction:Impulse oscillometry(IOS)employs high frequency sinusoidal or impulse pressure and flow waveforms to interrogate the mechanical properties of the respiratory system.It has special applications to preschool and younger children who may have difficulty performing the repetitive forced expiratory maneuvers required for spirometry.Case presentation:We present a case illustrating improvements of respiratory system mechanics measured by IOS in a 6-year-old child with cystic fibrosis(CF)who demonstrated clinical and radiological improvement after a course of therapy with hospitalization and intravenous antibiotics,and initiation of a cystic fibrosis transmembrane regulator(CFTR)protein corrector/potentiator agent.We also report a new finding:observed lower than expected reactance at low compared to high frequencies("reactance inversion").Conclusion:Reactance inversion may reflect parallel pathway inhomogeneities in resistance and elastance or intrabreath airway inertance changes in young children with CF.Further study is needed in children with airway obstruction due to asthma,cystic fibrosis,and chronic lung disease of infancy to demonstrate the prevalence of this finding and whether it is specific to a measurement device.展开更多
文摘In the past 40 years,advances in neonatal intensive care unit(NICU)technology have enabled premature infants with lower birth weight and younger gestational age to survive.But with it comes an increase in the incidence of long-term respiratory dysfunction,mainly in the form of bronchopulmonary dysplasia(BPD).Preventing lung injury is crucial for preventing BPD and improving the long-term prognosis of premature infants.Therefore,how to avoid ventilator-associated lung injury has become a focus of clinical and scientific research in premature infants in recent years.This article will elaborate on the susceptibility and pathophysiology of premature infant lung injury,ventilation strategies for preventing lung injury,and new advances in neonatal respiratory support.
文摘We aim to provide an up-to-date summary of infantile hepatic hemangioma(IHH) and its misnomers and to dialectically present the differential diagnosis of these rare entities of the liver.Eligible peer-reviewed articles on hepatic infantile hemangiomas,published between 2000 and 2015,were reviewed for this study.IHH is the most common hepatic vascular tumor in children.Once a liver mass is identified in an infant,the differential diagnosis ranges from vascular malformations to benign and malignant tumors including mesenchymal hamartoma,hepatoblastoma,metastatic neuroblastoma,so careful physical examination,imaging studies,and,if indicated,tumor markers and biopsy,are of pivotal importance to ascertain the correct diagnosis.Despite the benign nature of IHHs,some of these lesions may demand medical and/or surgical intervention,especially for multiple and diffuse IHH.Complications can include hepatomegaly,hypothyroidism and cardiac failure.Therefore,a close follow-up is required until complete involution of the lesions.We propose an algorithm to guide the physicians towards the proper management of hepatic lesions.
文摘This article provides a comprehensive overview of key issues related to pediatric drug development and rational dosing guidance in pediatrics with an emphasis on how pharmacometrics can improve the efficiency and productivity of pediatric trials.The pharmacokinetics(PK)and pharmacodynamics(PD)of drugs are often different between adult and pediatric populations which necessitate specific studies in children.The aims of this review are to discuss a number of recent methodological developments of modeling and simulation that facilitate the evaluation of drugs in pediatrics.Specific focus has been placed on addressing the key issues of PK/PD scaling,sparse sampling,colinearity,covariate evaluation,dose optimization for trial design and label,modeling strategies and validation approaches.The features and potential advantages of Bayesian hierarchical model,physiology-based PK models,and K-PD models are also presented.
基金National Science and Technology Major Project(2017ZX09304018).
文摘Background and purpose Rapid genotyping is useful for guiding early antiplatelet therapy in patients with high-risk nondisabling ischaemic cerebrovascular events(HR-NICE).Conventional genetic testing methods used in CYP2C19 genotype-guided antiplatelet therapy for patients with HR-NICE did not satisfy the needs of the Clopidogrel in High-Risk Patients with Acute Nondisabling Cerebrovascular Events(CHANCE)-2 trial.Therefore,we developed the rapid-genotyping GMEX(point-of care)system to meet the needs of the CHANCE-2 trial.Methods Healthy individuals and patients with history of cardiovascular diseases(n=408)were enrolled from six centres of the CHANCE-2 trial.We compared the laboratory-based genomic test results with Sanger sequencing test results for accuracy verification.Next,we demonstrated the accuracy,timeliness and clinical operability of the GMEX system compared with laboratory-based technology(YZY Kit)to verify whether the GMEX system satisfies the needs of the CHANCE-2 trial.Results Genotypes reported by the GMEX system showed 100%agreement with those determined by using the YZY Kit and Sanger sequencing for all three CYP2C19 alleles(*2,*3 and*17)tested.The average result’s turnaround times for the GMEX and YZY Kit methods were 85.0(IQR:85.0-86.0)and 1630.0(IQR:354.0-7594.0)min(p<0.001),respectively.Conclusions Our data suggest that the GMEX system is a reliable and feasible point-of care system for rapid CYP2C19 genotyping for the CHANCE-2 trial or related clinical and research applications.
文摘Cancer remains a major cause of human mortality. The greatest barrier to cure is resistance to conventional medi- cal treatments. Therapy resistance arises through clonal evolution driven by ge- nomic instability, fostered by selection as therapy-sensitive ceils are eradicated. Such resistance has been attributed to al- terations in numerous cellular pathways, yet many ultimately impact the process ofmitochondrial apoptosis. The critical gatekeepers for mitochondrial apoptosis initiation are the Bcl2-homology （BH） proteins, whose interactions integrate the varied stressors a cell encounters and provide a live-or-die decision （reviewed in [1]）. As such, BH proteins are the frequent target of alterations in cancer cells during oncogenesis and tumor progression [2].
文摘Chronic obstructive pulmonary disease(COPD)is a leading cause of disability and death of adults in the USA and worldwide.While environmental factors such as smoking and air pollution are major contributors to COPD,pediatric respiratory disease and more specifically early childhood wheezing are frequent predisposing factors.It is therefore possible that aggressive prevention and treatment of childhood respiratory illness may modify adult COPD risk.This article reviews some of the physiological factors that may explain the pediatric origins of childhood lung disease.One such factor is the"tracking"of normal lung function which occurs with growth.The maximal expiratory flow volume(MEFV)curve is an ideally suited tool to monitor tracking of airway function over the lifespan,as its relative effort independence makes it highly reliable.Study of the MEFV curve has demonstrated that individuals with similar lung volumes can have large differences in maximal flows,reflecting a disconnection between airway and lung growth("dysanapsis").Less than average airway size due to dysanaptic airway growth or airway remodeling may be independent risk factors for the development of COPD and the asthma/COPD overlap syndrome in adult life.There are intriguing early data suggesting that perhaps at least some of this risk is modifiable by improving asthma control with inhaled corticosteroids and minimizing asthma exacerbations.
文摘Objective:Because children with congenital hyperinsulinism(HI) caused by recessive loss of function mutations in the adenosine triphosphate (ATP)-dependent potassium channel(KATP-HI) are not leucine sensitive,we evaluated for protein induced hypoglycemia with oral protein tolerance tests. Study design:Blood glucose and insulin concentrations were measure devery 15 minutes for 3 hours after an oral protein loadin children with KATP-HI (n=11) and compared with those of children with glutamate dehydrogenase HI (n=12) and control subjects (n=12). Results:Similar to children with glutamate dehydrogenase HI,patients with KATP-HI displayed protein-induced hypoglycemia (10/11)with blood glucose concentrations declining by 17 to 69 mg/dL. In contrast,oral proteinhad little effect on blood glucose concentrations in control subjects.Conclusions:Protein induced hypoglycemia is a feature of KATP-HI,despite the absence of leucine sensitivity. The results indicate that amino acids can stimulate insulin secretionvia a glutamate dehydrogenase and KATP channel-independent pathway.
文摘Dear Sir,I n their article, ＂A comparison between monocanalicular and pushed monocanalicular silicone intubation in the treatment of congenital nasolacrimal duct obstruction＂, Andalib et al present the results of a prospective study on congenital nasolacrimal duct obstruction treated either with a Monoka stent （using a Crawford hook for nasal retrieval） or a Masterka pushed technique for insertion of the Masterka stent. The success rates were respectively 90% and 50%.
文摘We present a case report of a boy with biliary atresia who,after hepatoportoenterostomy performed on day 21 of life, had immediate resolution of cholestasis and remained anicteric until 3.5 months of age. He then abruptly developed acholic stools.Nuclear medicine imaging study showed no excretion. Broadspectrum antibiotics and corticosteroids were administered but did not lead to clinical improvement; a surgical revision of the original anastomosis was undertaken at 4 months of age. At 14 months of age, the child is anicteric and growing well. In this case, successful revision of hepatoportoenterostomy averted the need for liver transplantation.
文摘Objective:To evaluate risk factors for recurrent thrombosis in pediatric patients. Study design:This prospective observational cohort study enrolled 120 patients with acute venous thromboembolism from January 2003 to April 2005. Datacollection included medical and family history,radiologic and laboratory studies,therapy,and follow-up. Results:The overall prevalence of recurrent thrombosis in our cohort was 19/120(15.8%). Patients with recurrence were older,with a median age of 14.8 years (range 2 weeks-23.6 years),compared with 10.1years (range newborn 23.4 years) in patients without recurrence(P = 0.03). Six of the 19 patients with recurrent thrombosis had cystic fibrosis (CF),compared with 0/101without recurrence (P< 0.001). Five of these 6 patients were colonized with Burkholderia cepacia in their sputum. Central venous catheters were associated with most,but not all,of the thromboses in patients with CF. Conclusions:In this study,patients with CF had a high risk of recurrent venous thrombosis,as well as a high prevalence of colonization with B cepacia. The cause of this risk has not been defined. This observation may have important implications for thromboprophylaxis,particularly in the setting of central venous catheters.
文摘Increased resting energy expenditure (REE) is a possible explanation for the negative energy balance seen in children with Alagille syndrome (AGS).We evaluated 16 subjects with AGS and 37 healthy controls and did not find a significant difference in REE (101%±12%,105%±13%,respectively).
文摘Background:To describe the sleep patterns of children below 36 months in Hong Kong,and evaluate the associations between parental behaviors and childhood sleep/wake patterns.Methods:Parents of 1049 infants and toddlers completed an internet-based expanded version of the Brief Infant Sleep Questionnaire.Results:Total sleep duration (P<0.001),frequency (P<0.001) and duration (P<0.001) of nocturnal awakenings decreased with age,whereas the longest sleep duration (P<0.001) and nocturnal sleep duration (P<0.001) increased with age.Children who room-or bed-shared with parents had later bedtimes (P<0.001),but similar sleep duration compared with those who had a separate sleep location.Falling asleep independently was associated with longer nocturnal sleep duration (P<0.001) and less sleep awakenings (P<0.001).Full-time employment of parents was associated with shorter total sleep duration of children (P<0.001).Although breastfeeding was associated with more nocturnal awakenings (P<0.001),no association was detected between breastfeeding and shorter sleep duration in children.Conclusions:As infants and toddlers develop,their sleep consolidates.Falling asleep independently was associated with longer nocturnal sleep duration and fewer sleep awakenings,whereas sleep location was not.This is an important finding,especially for families with limited living space where parent/ child room-or bed-sharing cannot be avoided.
基金This study is supported by the National Natural Science Foundation of China(#81620108020 to DG and#81801574 to PH)Guangdong Province"Pearl River Talent Plan"Innovation and Entrepreneurship Team Project(2019ZT08Y464 to CL)+1 种基金Shenzhen Science and Technology Program(#JCYJ20200109142201695 and#KQTD20180411143323605 to DG and#JCYJ20190807161415336 to PH)DG is also supported by the Guangdong Zhujiang Talents Programme and the National Ten-thousand Talents Programme.
文摘DNA sensing and timely activation of interferon(IFN)-mediated innate immunity are crucial for the defense against DNA virus infections and the clearance of abnormal cells.However,overactivation of immune responses may lead to tissue damage and autoimmune diseases;therefore,these processes must be intricately regulated.STING is the key adaptor protein,which is activated by cyclic GMP-AMP,the second messenger derived from cGAS-mediated DNA sensing.Here,we report that CCDC50,a newly identified autophagy receptor,tunes STING-directed type I IFN signaling activity by delivering K63-polyubiquitinated STING to autolysosomes for degradation.Knockout of CCDC50 significantly increases herpes simplex virus 1(HSV-1)-or DNA ligand-induced production of type I IFN and proinflammatory cytokines.Ccdc50-deficient mice show increased production of IFN,decreased viral replication,reduced cell infiltration,and improved survival rates compared with their wild-type littermates when challenged with HSV-1.Remarkably,the expression of CCDC50 is downregulated in systemic lupus erythematosus(SLE),a chronic autoimmune disease.CCDC50 levels are negatively correlated with IFN signaling pathway activation and disease severity in human SLE patients.CCDC50 deficiency potentiates the cGAS-STING-mediated immune response triggered by SLE serum.Thus,our findings reveal the critical role of CCDC50 in the immune regulation of viral infections and autoimmune diseases and provide insights into the therapeutic implications of CCDC50 manipulation.
文摘Preschool children with asthma present a challenge in lung function testing, as they cannot readily cooperate with spirometry. The forced oscillation technique (FOT) measures passive pressures and flows delivered by a loudspeaker to a facemask, at frequencies much higher than those occurring physiologically. This in turn allows for rapid collection of data from a spontaneously breathing child in a timespan of seconds. However, at very rapid oscillatory flow rates, the mechanical properties opposing flows into and out of the respiratory system (collectively termed the respiratory system impedance, and comprised of elastic, resistive and inertial components) are very different from at normal breathing frequencies, with elastic properties being less important and inertial properties being more important. An understanding of how the respiratory system behaves at high frequencies is essential to understanding the physiological basis of this technique. This article presents a way to understand these oscillatory mechanics of the respiratory system. It then describes studies of the FOT in normal preschool children and in children with asthma. The technique can also measure the separate contributions of the central and peripheral airways, as well as assess for changes after bronchodilator administration. The FOT holds promise for the objective measurement of lung function in children who are too young to reliably perform spirometry.
文摘Introduction:Impulse oscillometry(IOS)employs high frequency sinusoidal or impulse pressure and flow waveforms to interrogate the mechanical properties of the respiratory system.It has special applications to preschool and younger children who may have difficulty performing the repetitive forced expiratory maneuvers required for spirometry.Case presentation:We present a case illustrating improvements of respiratory system mechanics measured by IOS in a 6-year-old child with cystic fibrosis(CF)who demonstrated clinical and radiological improvement after a course of therapy with hospitalization and intravenous antibiotics,and initiation of a cystic fibrosis transmembrane regulator(CFTR)protein corrector/potentiator agent.We also report a new finding:observed lower than expected reactance at low compared to high frequencies("reactance inversion").Conclusion:Reactance inversion may reflect parallel pathway inhomogeneities in resistance and elastance or intrabreath airway inertance changes in young children with CF.Further study is needed in children with airway obstruction due to asthma,cystic fibrosis,and chronic lung disease of infancy to demonstrate the prevalence of this finding and whether it is specific to a measurement device.
