The N-Myc-responsive lncRNA MILIP promotes DNA double-strand break repair through non-homologous end joining.

The protooncoprotein N-Myc, which is overexpressed in approximately 25% of neuroblastomas as the consequence of MYCN gene amplification, has long been postulated to regulate DNA double-strand break (DSB) repair in neuroblastoma cells, but experimental evidence of this function is presently scant. Here, we show that N-Myc transcriptionally activates the long noncoding RNA MILIP to promote nonhomologous end-joining (NHEJ) DNA repair through facilitating Ku70-Ku80 heterodimerization in neuroblastoma cells. High MILIP expression was associated with poor outcome and appeared as an independent prognostic factor in neuroblastoma patients. Knockdown of MILIP reduced neuroblastoma cell viability through the induction of apoptosis and inhibition of proliferation, retarded neuroblastoma xenograft growth, and sensitized neuroblastoma cells to DNA-damaging therapeutics. The effect of MILIP knockdown was associated with the accumulation of DNA DSBs in neuroblastoma cells largely due to decreased activity of the NHEJ DNA repair pathway. Mechanistical investigations revealed that binding of MILIP to Ku70 and Ku80 increased their heterodimerization, and this was required for MILIP-mediated promotion of NHEJ DNA repair. Disrupting the interaction between MILIP and Ku70 or Ku80 increased DNA DSBs and reduced cell viability with therapeutic potential revealed where targeting MILIP using Gapmers cooperated with the DNA-damaging drug cisplatin to inhibit neuroblastoma growth in vivo. Collectively, our findings identify MILIP as an N-Myc downstream effector critical for activation of the NHEJ DNA repair pathway in neuroblastoma cells, with practical implications of MILIP targeting, alone and in combination with DNA-damaging therapeutics, for neuroblastoma treatment.

Rotavirus hospitalization in early childhood: fine motor skills and cognition at six years old-Population-based cohort study.

Rotavirus is linked to severe childhood gastroenteritis and neurological complications, but its impact on neurodevelopment remains uncertain. We examined data from 1,420,941 Korean children born between 2009 and 2011, using the Korean National Health Insurance System. At age 6, we assessed neurodevelopmental outcomes using the validated Korean Developmental Test, covering six major domains. Utilizing propensity score-based Inverse Probability Weighting to ensure covariates including considering covariates including sex, birth weight, changes in body weight from birth to 4-6 months of age, head circumference at 4-6 months of age, residence at birth, economic status, infant feeding types, and birth year. The main analysis that encompassed 5,451 children with rotavirus hospitalization and 310,874 unexposed individuals reveled heightened odds of suspected delays in fine motor skills and cognition among exposed children. Our results suggest an association between rotavirus-related hospitalization in infancy and suspected delays in fine motor function and cognition in 6-year-olds.

Comprehensive analysis of somatic mutations and structural variations in domestic pig.

Understanding somatic mutations and structural variations in domestic pigs (Sus scrofa domestica) is critical due to their increasing importance as model organisms in biomedical research. In this study, we conducted a comprehensive analysis through whole-genome sequencing of skin, organs, and blood samples. By examining two pig pedigrees, we investigated the inheritance and sharedness of structural variants among fathers, mothers, and offsprings. Utilizing single-cell clonal expansion techniques, we observed significant variations in the number of somatic mutations across different tissues. An in-house developed pipeline enabled precise filtering and analysis of these mutations, resulting in the construction of individual phylogenetic trees for two pigs. These trees explored the developmental relationships between different tissues, revealing insights into clonal expansions from various anatomical locations. This study enhances the understanding of pig genomes, affirming their increasing value in clinical and genomic research, and provides a foundation for future studies in other animals, paralleling previous studies in mice and humans. This approach not only deepens our understanding of mammalian genomic variations but also strengthens the role of pigs as a crucial model in human health and disease research.

Viral respiratory infections requiring hospitalization in early childhood related to subsequent asthma onset and exacerbation risks.

Viral lower respiratory tract infections (LRTIs), including rhinovirus and respiratory syncytial virus during early childhood, have been linked to subsequent asthma. However, the impact of other respiratory viruses remains unclear. We analyzed nationwide Korean data from January 1, 2008, to December 31, 2018, utilizing the national health insurance database. Our study focused on 19 169 meticulously selected children exposed to severe respiratory infections requiring hospitalization with documented viral pathogens, matched with 191 690 unexposed children at a ratio of 1:10 using incidence density sampling. Our findings demonstrate that asthma exacerbation rates were higher among the exposed cohort than the unexposed cohort over a mean follow-up of 7.8 years. We observed elevated risks of asthma exacerbation and newly developed asthma compared to the unexposed cohort. Hospitalization due to rhinovirus, respiratory syncytial virus, influenza, metapneumovirus, and adenovirus was related to increased asthma exacerbations. Notably, we found a stronger association in cases of multiple LRTI hospitalizations. In conclusion, our study shows that early childhood respiratory viral infections are related to subsequent asthma exacerbations and new asthma diagnoses.

Cascade of atopic dermatitis comorbidities in children after birth for 15 years.

BACKGROUND: Individuals with atopic dermatitis often develop other conditions. OBJECTIVE: This study aimed to determine how atopic dermatitis comorbidities develop in children over time. METHODS: This population-based administrative cohort study used national health insurance data. We traced individuals born in Korea between 2002 and 2003 to 2018. The date of initial atopic dermatitis diagnosis was set as the index date. Fifty-three childhood comorbidities of atopic dermatitis were identified as outcomes of interest by performing a comprehensive literature search and comparing the prevalence of diagnostic codes in children with and without atopic dermatitis. Four control children per individual in the atopic dermatitis group were randomly matched based on sex and index date. The association between atopic dermatitis and the development of each specified disease was assessed using proportional hazard assumption, followed by mapping of the temporal sequences of interconnected comorbidities. RESULTS: The atopic dermatitis and control groups contained 67,632 and 270,528 individuals, respectively. The median age at the index date was 10 months, whereas the median follow-up period was 15 years. Twenty diseases that were associated with a higher risk of atopic dermatitis were identified and a chain of interconnected conditions created. The progression began in childhood with febrile seizures, constipation, and asthma, and was later associated with the emergence of food allergy, allergic rhinitis, psychiatric disorders, and autoimmune diseases. CONCLUSION: Our study highlights the temporal nature of atopic dermatitis comorbidities in children, and indicates that an understanding of the comorbidities may inform its clinical management and treatment.

Neurodevelopment in Term Infants with Normal Birthweight following Postnatal Systemic Steroid Exposure.

INTRODUCTION: Studies investigating the potential impact of systemic steroid exposure during early infancy on neurological development in full-term infants with normal birth weight are lacking. METHODS: This population-based administrative cohort study used data of national health insurance and a health-screening program for infants and children and included full-term infants who were born in Korea between 2008 and 2012 with normal birth weight and did not have any specific perinatal or neurodevelopmental diseases. The prescription of systemic steroids within the first 3 months of age was mainly considered. The neurological development of children was assessed using the Korean Development Screening Test (K-DST) at 6 years of age. To balance the baseline characteristics of the control and exposed groups, stabilized inverse probability of treatment weighting with trimming was performed in the main cohort. Ordinal logistic regression was used to assess the association between systemic steroid exposure and unfavorable results in the K-DST. RESULTS: The control and exposure groups had 246,168 and 5,083 children, respectively. The K-DST suggested unfavorable results in 8.1% and 8.6% children in the control and exposure groups, respectively (weighted odds ratio, 95% confidence interval, 1.03, 0.93-1.14). When each domain of the K-DST was considered separately, the risk of unfavorable results in the exposed group was not significantly different from that in the control group. CONCLUSIONS: No significant association was observed between exposure to systemic steroids during early infancy and neurodevelopmental impairment at 6 years of age.

Associations of personal urinary volatile organic compounds and lung function in children.

BACKGROUND: We investigated the correlation between urine VOC metabolites and airway function in children exposed to anthropogenic volatile organic compounds (VOCs), notable pollutants impacting respiratory health. METHODS: Out of 157 respondents, 141 completed skin prick tests, spirometry, IOS, and provided urine samples following the International Study of Asthma and Allergies in Childhood (ISAAC)-related questions. Allergic sensitization was assessed through skin prick tests, and airway functions were evaluated using spirometry and impulse oscillometry (IOS). Forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC) was recorded and FEV1/FVC ratio was calculated. Airway mechanics parameters including respiratory resistance at 5 Hz (Rrs5) mean respiratory resistance between 5 Hz and 20 Hz (Rrs5-20), were also recorded. Urine concentrations of metabolites of benzene, ethylbenzene, toluene, xylene, styrene, formaldehyde, carbon-disulfide were analyzed by gas chromatography/tandem mass spectroscopy. RESULTS: The median age at study participation was 7.1 (SD 0.3) years. Muconic acid (benzene metabolites) and o-methyl-hippuric acid (xylene metabolites) above medians were associated with a significant increase in Rrs5 (muconic acid: aß = 0.150, p = .002; o-methyl-hippuric acid: aß = 0.143, p = .023) and a decrease in FEV1/FVC (o-methyl-hippuric acid: aß = 0.054, p = .028) compared to those below median. No associations were observed for Rrs5-20 and FEV1 between the groups categorized as above and below the median (all parameter p values > .05). CONCLUSIONS: Elevated levels of benzene and xylene metabolites were associated with a significant increase in Rrs5 and a decrease in FEV1/FVC, related to increased resistance and restrictive lung conditions compared to individuals with concentrations below the median.

The association between phthalate exposure and pubertal development.

Antiandrogenic effect of phthalates have been reported; however, results regarding the effect of phthalate exposure in pubertal children have been inconsistent. We aimed to investigate the relationship between phthalate exposure and pubertal development, especially whether high molecular weight phthalates (HMWP) and low molecular weight phthalates (LMWP) are differently associated in boys and girls. Urinary phthalate metabolites (4 HMWPs and 3 LMWPs) in Korean children (236 boys and 202 girls, aged 10 to 12 years) were measured. The association between phthalate levels and pubertal development (pubertal stages self-reported by parents and sex steroid levels) was analyzed by generalized linear regression after adjusting for age, body mass index z score, and premature birth and/or low birth weight. Both the highest quartile of HMWP (Q4 vs Q1, adjusted odds ratio [OR], 0.238; 95% confidence interval [CI], 0.090-0.627; p = 0.004) and LMWP (Q4 vs Q1, adjusted OR, 0.373; 95% CI, 0.151-0.918; p = 0.032) were inversely associated with pubertal stages in boys, whereas the highest quartile of LMWP (Q4 vs Q1, adjusted OR, 2.431; 95% CI, 1.024-5.768; p = 0.044) was significantly related to advanced pubertal stages in girls. Testosterone levels in boys were significantly lower at the highest quartile of HMWP (adjusted ß = - 0.251; 95% CI, - 0.476 to - 0.027; p = 0.028). However, in girls, we could not find any significant relationship between HMWP or LMWP and estradiol levels. CONCLUSIONS: Our results suggest that phthalate exposure, especially exposure to the HMWP, may have inverse association with male pubertal development. Further investigation is required to verify the relationship of phthalate exposure and pubertal development in girls. WHAT IS KNOWN: • Exposure to phthalates may have antiandrogenic effects. • Studies on the association between phthalates and pubertal development have yielded inconsistent results. WHAT IS NEW: • Phthalate levels were inversely associated with self-reported pubertal stages in boys. • Exposure to phthalates might have a negative influence on male pubertal development.

Successful treatment with rituximab in anti-phospholipid syndrome nephropathy associated with systemic lupus erythematosus: A case report and literature review.

Anti-phospholipid syndrome (APS) nephropathy is an autoimmune disease that is sometimes accompanied by systemic lupus erythematosus (SLE). Here, we report the use of rituximab to treat a case of APS nephropathy in a SLE patient with recurrent vascular thrombosis. A 52-year-old woman, who had been diagnosed with SLE 11 years earlier, was referred to a nephrology clinic for evaluation of azotaemia and proteinuria. She had experienced spontaneous abortion at 35 years of age. The patient had been diagnosed with right popliteal thrombosis at 39 years of age, and with left pulmonary artery thrombosis and SLE at 41 years of age. Before admission, she was undergoing anticoagulant and immunosuppressive therapies, with follow-up in the rheumatology clinic. At her last outpatient clinic visit before admission, she exhibited mild bilateral lower-limb pitting oedema, impaired renal function and proteinuria. Renal biopsy revealed arteriolar wall thickening, with thrombi in the capillary lumina and marked inflammatory cell infiltration in the interstitium. The patient was treated with warfarin and high-dose corticosteroids. Intravenous rituximab (500 mg) was also administered twice at a 4-week interval. Her renal function did not worsen any further, and her proteinuria decreased. Here we report the successful use of rituximab to treat APS nephropathy in a patient with SLE, who had progressive renal insufficiency.

Consumption of Sugar-Sweetened Beverages before 2 Years of Age and Attention-Deficit/Hyperactivity Disorder.

INTRODUCTION: This study examined the association between sugar-sweetened beverage consumption before the first 24 months of life and attention-deficit/hyperactivity disorder (ADHD). METHODS: A population administrative cohort study was conducted in Korea (2008-2019) using linked national insurance data and a health screening survey. The cohort included 25,305 children in the exposed group with high sugar-sweetened beverage drinks (≥200 mL) and 339,931 in the reference groups (<200 mL) at 24 months of age. The primary outcome was the development of ADHD based on the International Classification of Disease (ICD) codes. Cox proportional model was used to identify the association between sugar-sweetened beverage consumption during early childhood and the later development of ADHD while controlling for multiple risk factors. RESULTS: Over a mean follow-up period of 9.2 years, the incidence rates of ADHD were 29.6 and 23.8 per 10,000 person-years in the exposed and reference groups, respectively. Compared with the reference group, children consuming high-sugar drinks were at an increased risk of ADHD (adjusted hazard ratio 1.17, 95% confidence interval [CI] 1.08-1.27). These associations remained significant even after applying alternative ADHD definitions or adjusting for confounding variables. CONCLUSION: Children who consume sweetened beverages during early childhood are at increased risk of developing ADHD later in life.

Trends in Incidence and Drug Prescriptions for Croup in Children Under 5 Years of Age: A 2002-2019 Population-Based Study.

BACKGROUND: Tracking national croup trends can provide important insights for childhood health management. This study aimed to analyze the incidence and drug prescription trends in Korean children over a two-decade period. METHODS: This population-based study encompassed 479,783 children aged < 5 years from 2002-2019, utilizing the National Health Insurance Service-National Sample Cohort. We identified participants with a primary croup diagnosis who were admitted to or visited the emergency room. Age-specific and age-adjusted incidence rates/10,000 person-years were calculated. We assessed using orthogonal polynomial contrasts and stratified by various factors (sex, age, residential area, economic status, comorbidities, and healthcare facility types). We observed changes in the use of five medications: inhaled steroids, systemic steroids, inhaled epinephrine, antibiotics, and short-acting bronchodilators. Generalized binomial logistic regression was used to analyze factors influencing prescription strategies. RESULTS: In 2002, the croup-related visits were 16.1/10,000 person-years, increasing to 98.3 in 2019 (P for trend < 0.001). This trend persisted, regardless of age, sex, region, and economic status. Children with comorbid atopic dermatitis or asthma maintained consistent croup rates, while those without comorbidities increased. Treatment trends showed decreasing antibiotic (73-47%) and oxygen use (21.3-3.4%), with increasing nebulized epinephrine (9.3-41.5%) and multiple drug prescriptions (67.8-80.3%). Primary care centers exhibited a greater increase in prescription usage and hospitalization duration than did tertiary healthcare institutions. CONCLUSION: Over the past two decades, croup incidence has risen, accompanied by increased epinephrine use and decreased antibiotic prescriptions. Longer hospitalization and higher medication use were mainly observed in primary care facilities.

Prospective Clinical Trial for Predicting Mastectomy Skin Flap Necrosis with Indocyanine Green Angiography in Implant-Based Prepectoral Breast Reconstruction.

BACKGROUND: Indocyanine green angiography (ICG-A) is a useful tool for evaluating mastectomy skin flap (MSF) perfusion during breast reconstruction. However, a standardized protocol for interpreting and applying MSF perfusion after mastectomy has not been established yet. The purpose of this study is to establish criteria for assessing MSF perfusion in immediate implant-based prepectoral breast reconstruction while correlating ICG-A findings with postoperative outcomes METHODS: This prospective observational study was conducted at a single institution and involved patients with breast cancer who underwent mastectomy and immediate implant-based prepectoral breast reconstruction between August 2021 and August 2023. The terms "hypoperfused flap" and "hypoperfused area" were defined according to ICG-A perfusion. MSF exhibited < 30% perfusion, excluding the nipple and the corresponding region, respectively. Data on the hypoperfused flap, hypoperfused area, and MSF necrosis were collected. RESULTS: Fifty-three breast cases were analyzed. Eight patients developed MSF necrosis (15.1%, 8/53). Of these, two patients underwent surgical debridement and revision within 3 months (3.8%, 2/53). There were nine cases of a hypoperfused flap, eight of which developed MSF necrosis. The hypoperfused flap was a significant predictor of the occurrence of MSF necrosis (p < 0.001). There was a tendency for increased full-thickness necrosis with a wider hypoperfused area. CONCLUSIONS: The hypoperfused flap enabled the prediction of MSF necrosis with high sensitivity, specificity, positive predictive value, and negative predictive value. Considering the presumed correlation between the extent of the hypoperfused area and the need for revision surgery, caution should be exercised when making intraoperative decisions regarding the reconstruction method. LEVEL OF EVIDENCE III: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Comparative In Vivo Study of Solid-Type Pure Hyaluronic Acid in Thread Form: Safety and Efficacy Compared to Hyaluronic Acid Filler and Polydioxanone Threads.

INTRODUCTION: Although various products are commonly used for skin rejuvenation, solid-type hyaluronic acid (HA) as an injectable form has not been researched or utilized. This study aimed to demonstrate the safety and efficacy of solid-type HA in thread form, which differs from the conventional gel-type HA commonly used. METHOD: Solid-type HA threads, conventional HA fillers, and polydioxanone (PDO) threads were inserted into the dorsal subcutaneous layer of mice. Photographs were taken on days 0, 1, 3, and 7, and on day 7, the samples were harvested for histological analysis. Inflammatory reactions and detection of collagen were confirmed through tissue staining, and real-time PCR was conducted to quantify collagen synthesis. RESULTS: In the histological analysis, the PDO threads exhibited a greater inflammatory response compared to the HA threads. Masson's trichrome staining revealed a higher degree of collagen synthesis in the HA thread group compared to the HA filler group. While collagen type 1 expression was significantly higher in the PDO thread group than in the HA thread group, the HA thread group showed higher expression levels of collagen type 3. Furthermore, the PDO thread group demonstrated a statistically significant increase in TGF-ß1 compared to the HA group. CONCLUSION: This in vivo study demonstrated the stable application of solid-type pure HA threads and their potential for inducing collagen production, while also yielding a low inflammatory response. The findings highlight the promising applications of solid-type HA in the field of cosmetic dermatology. NO LEVEL ASSIGNED: This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Efficacy of Integrated Risk Score Using Omics-Based Biomarkers for the Prediction of Acute Rejection in Kidney Transplantation: A Randomized Prospective Pilot Study.

Acute rejection (AR) is critical for long-term graft survival in kidney transplant recipients (KTRs). This study aimed to evaluate the efficacy of the integrated risk score of omics-based biomarkers in predicting AR in KTRs. This prospective, randomized, controlled, multicenter, pilot study enrolled 40 patients who recently underwent high-immunologic-risk kidney transplantation (KT). Five omics biomarkers were measured, namely, blood mRNA (three-gene signature), urinary exosomal miRNA (three-gene signature), urinary mRNA (six-gene signature), and two urinary exosomal proteins (hemopexin and tetraspanin-1) at 2 weeks and every 4 weeks after KT for 1 year. An integrated risk score was generated by summing each biomarker up. The biomarker group was informed about the integrated risk scores and used to adjust immunosuppression, but not the control group. The outcomes were graft function and frequency of graft biopsy. Sixteen patients in the biomarker group and nineteen in the control group completed the study. The mean estimated glomerular filtration rate after KT did not differ between the groups. Graft biopsy was performed in two patients (12.5%) and nine (47.4%) in the biomarker and control groups, respectively, with the proportion being significantly lower in the biomarker group (p = 0.027). One patient (6.3%) in the biomarker group and two (10.5%) in the control group were diagnosed with AR, and the AR incidence did not differ between the groups. The tacrolimus trough level was significantly lower in the biomarker group than in the control group at 1 year after KT (p = 0.006). Integrated omics biomarker monitoring may help prevent unnecessary or high-complication-risk biopsy and enables tailored immunosuppression by predicting the risk of AR in KTRs.

Total airway mechanics and fractional exhaled nitric oxide levels of children living in banjihas (semi-basements).

BACKGROUND: The ISAAC phase III study in Korea found a higher incidence of wheezing illnesses among residents in basements or semi-basements. OBJECTIVE: This study investigates the link between living in banjihas (semi-basements) and airway resistance and Th2 airway inflammation in Korean children, compared to those on higher floors. METHODS: We assessed 575 fifth- and sixth-grade students (aged 10-12) in an inner-city area of South Korea. The study utilized impulse oscillometry to measure small and total airway resistance (Rrs20-5 and Rrs0, respectively) and Fractional Exhaled Nitric Oxide (FeNO) measurements to evaluate airway inflammation. We also considered a range of biological and environmental factors, including allergen sensitization, serum 25-hydroxyvitamin D levels, and urinary metabolites like VOCs, bisphenol, and triclosan. Participants were categorized by living floors: banjihas, first-fifth floors, and sixth floors or higher. RESULTS: Twenty-five children (4.3%) lived in banjihas, 311 (54.1%) on the first to fifth floor, and 239 (41.6%) on the sixth floor or above. Despite similar levels of allergen sensitization and urinary pollutant metabolite levels across all groups, banjiha dwellers showed significantly higher total airway resistance (adjusted &1: 0.633, 95%CI: 0.156, 1.109; P = 0.009) and a greater prevalence of elevated FeNO levels (> 35 ppb) (P = 0.033). These findings persisted after adjusting for critical factors like height, gender, BMI z-score, and birth conditions. CONCLUSION: Children in banjihas exhibit elevated airway resistance and FeNO levels independently of allergen sensitization or pollution exposure, underscoring the necessity for enhanced focus on their respiratory health in such living conditions.

Unraveling the link between atopic dermatitis and autoimmune diseases in children: Insights from a large-scale cohort study with 15-year follow-up and shared gene ontology analysis.

BACKGROUND: Atopic dermatitis and autoimmune diseases are highly heritable conditions that may co-occur from an early age. METHODS: The primary study is a national administrative cohort study involving 499,428 children born in 2002, tracked until 2017. Atopic dermatitis was defined as five or more principal diagnoses of atopic dermatitis and two or more topical steroid prescriptions. We estimated the risks for the occurrence of 41 autoimmune diseases, controlling for risk factors. In addition, we sourced a gene library from the National Library of Medicine to conduct a comprehensive gene ontology. We used Gene Weaver to identify gene set similarity and clustering, and used GeneMania to generate a network for shared genes. RESULTS: Exposed and unexposed groups included 39,832 and 159,328 children, respectively. During a mean follow-up of 12 years, the exposed group had an increased risk of autoimmune disease (hazard ratio, 1.27 [95 % confidence interval, 1.23-1.32]) compared to the unexposed group. The hazard ratios of autoimmune illnesses consistently increased with two- and five years lag times and alternative atopic dermatitis definitions. Shared genes between atopic dermatitis and autoimmune diseases were associated with comorbidities such as asthma, bronchiolitis, and specific infections. Genetic interactions of these shared genes revealed clustering in Th1, Th2, Th17, and non-classifiable pathways. CONCLUSIONS: Atopic dermatitis was significantly associated with an increased risk of subsequent autoimmune disease. we identified the genetically associated disease in atopic dermatitis patients comorbid with autoimmune disease and demonstrated a genetic network between atopic dermatitis and autoimmune diseases.

Growth pattern during early infancy, body mass index during childhood and childhood asthma.

BACKGROUND: There is a lack of longitudinal studies of associations between growth from infancy to childhood and asthma development. OBJECTIVE: The objective of the study was to investigate the effects of weight change during infancy, body mass index (BMI) and the interaction of these factors on the risk of childhood asthma. METHODS: We enrolled children born in 2008 and 2009 at full-term and with normal birth weight. The weight change in infancy was grouped into slow, on-track and rapid. BMI status in childhood was stratified into low, normal and high groups and used as a time-varying variable. The outcome was asthma, defined as two or more diagnoses of asthma separated by at least 1 year after 2 years of age. The risk of asthma was assessed using Cox proportional hazard regression, with adjustment for sex, residence area at birth, economic status and feeding types in infancy. RESULTS: Of 917,707 children born in Korea in 2008 and 2009, 271,871 were eligible for analysis. The risk of asthma was greater in groups with low birth weight (aHR 1.06, 95% CI 1.04 to 1.08), rapid body weight change during early infancy (aHR 1.08, 95% CI 1.07 to 1.10) and high BMI during childhood (aHR 1.06, 95% CI 1.04-1.08). The interaction of weight change during early infancy with BMI during childhood was significant for asthma (p < .01). Rapid weight gain in infancy was associated with lower risk of asthma in those with low BMI during childhood; had no association with asthma in those with normal BMI during childhood; and was associated increased asthma risk in those with high BMI during childhood-aHR 1.26 (95% CI 1.19 to 1.33) and aHR 1.33 (95% CI 1.12 to 1.56) compared with on-track and slow infant weight gain, respectively. CONCLUSION: Low birth weight, high BMI during childhood and, in those with high childhood BMI, rapid weight gain during early infancy are associated with increased risk of childhood asthma.

Relationship Between Feeding to Sleep During Infancy and Subsequent Childhood Disease Burden.

OBJECTIVE: To investigate the association of feeding to sleep during infancy and subsequent childhood health burdens. STUDY DESIGN: Information was collected from the parents of children who participated in the national health screening survey when the child was 9-12 months old. The exposure group included participants who were fed to sleep. The primary outcome was all-cause hospital admission (inpatient care, intensive care unit [ICU] admission, or general anesthesia) after age 24 months. Secondary outcomes were subsequent childhood diseases (ie, adenoidectomy and/or tonsillectomy, nasal polyps, allergic rhinitis, acute otitis media, asthma, pneumonia, and aspiration pneumonia), and growth status, as measured by weight-to-age and height-to-age z-scores. RESULTS: The study cohort consisted of 224 075 children who participated in the health screening program, 29 392 of whom (13.1%; 51% males) were fed to sleep. Exposure was associated with an increased risk of all-cause hospitalization after age 24 months (hazard ratio [HR], 1.05; 95% CI, 1.03-1.07), but not with admission to an ICU or receipt of general anesthesia. This also was related to adenoidectomy and/or tonsillectomy (HR, 1.08; 95% CI, 1.01-1.15), dental caries (HR, 1.32; 95% CI, 1.23-1.40), asthma (HR, 1.14; 95% CI, 1.14-1.24), pneumonia (HR, 1.10; 95% CI, 1.07-1.13), overweight (HR, 1.06; 95% CI, 1.03-1.09), and obesity (HR, 1.11; 95% CI, 1.06-1.16). CONCLUSIONS: Several adverse health outcomes are related to feeding to sleep during early childhood.

Acquired susceptibility to autoimmune diseases in pediatric patients with Escherichia coli infection: A population-matched retrospective cohort study.

BACKGROUND: Escherichia coli (E.coli) infection has been proposed to play an important role as an initial trigger in the development of autoimmunity via molecular mimicry. However, there has been no preliminary cohort study to establish the association of E.coli infection with autoimmune diseases. Therefore, we conducted a large scale, population-matched cohort study to determine the risk of autoimmune disease among patients with exposure to E.coli. METHODS: Utilizing the National Health Insurance Service database, we retrospectively analyzed a total of 259,875 Korean children that consisted of 23,625 exposed and 236,250 unexposed persons from January 1, 2002 to December 31, 2017. The exposed cohort was defined as patients diagnosed with E.coli infection. Unexposed controls were matched by birth year and sex at a 1:10 ratio for each exposed patient, using incidence density sampling. The primary outcome was autoimmune disease development. We used the Cox model to estimate the risks of autoimmune diseases among patients diagnosed with E.coli infection. RESULTS: Over a mean follow-up of 10 years, there were 1455 autoimmune disease cases among exposed patients (incidence rate, 63.6 per 10,000 person-years) and 11,646 autoimmune disease cases among unexposed persons (incidence rate, 50.4 per 10,000 person-years), with an adjusted hazard ratio (HR) of 1.254 (95% CI 1.187-1.325). E.coli infection was associated with increased risks of autoimmune diseases; Reactive arthritis, HR 1.487, 95% CI 1.131-1.956; Henoch Schönlein purpura, HR 1.265, 95% CI 1.050-1.524; Systemic lupus erythematosus, HR 1.838, 95% CI 1.165-2.898; Sjögren's syndrome, HR 2.002, 95% CI 1.342-2.987; IgA nephropathy, HR 1.613, 95% CI 1.388-1.874. Kaplan-Meier cumulative incidence curves also showed a significant association between E.coli infection and incident autoimmune disease (p < 0.0001). This relationship was not only independent of demographic variables, but also remained consistent across various sensitivity analyses. On the other hand, patients with longer hospital stay for E.coli infection were at a higher risk of autoimmune disease (p = 0.0003), and the risk of autoimmune disease also tended to increase, as the frequency of E.coli infection was higher. Moreover, the relative risk of autoimmune disease seemed to be attenuated by use of antibiotics and a history of intestinal infectious disease, but elevated by coexistence of other autoimmune diseases. CONCLUSIONS: Our cohort study indicates that E.coli infection was significantly associated with increased susceptibility to autoimmune diseases, even after adjusting for different factors. Thus, among environmental factors, a previous history of E.coli infection could be a predisposing risk factor in the development of autoimmune diseases.

Association between atopic dermatitis and school readiness in preschool children.

BACKGROUND: Although atopic dermatitis (AD) in children affects diverse stages of life, no studies have reported on the association between school readiness and AD. METHODS: This study used Korean National Health Insurance data and the Health Screening Program for Infants and Children. Among all children born between 2008 and 2012 in Korea, those who were assessed for school readiness through questionnaires in a health screening program performed at 54 and 60 months old were enrolled. AD was defined based on the International Classification of Diseases codes, with two or more prescriptions of topical corticosteroids during the first 54-60 months of life. The primary outcome was the association between school readiness and AD. The questionnaire relating to school readiness comprised six items - cognitive skills, social development, activeness, concentration, emotional development, and language skills. Logistic regression analysis was used to identify the associations between school readiness and AD. RESULTS: This study included 239,673 children without AD and 38,229 children with AD. The average age at which school readiness was assessed was 4.8 years. AD was associated with vulnerability in activeness (adjusted odds ratio: 1.127; 95% confidence interval: 1.071-1.186) and concentrations (1.170; 1.093-1.254). The impact of AD on concentrations showed consistent results regardless of sex, exposure to systemic corticosteroids and antihistamines, and age at the diagnosis of AD. CONCLUSIONS: Children with AD have vulnerability in school readiness in the aspects of activeness and concentration.