Background: Achieving a definitive genetic diagnosis of unexplained multiple congenital anomalies (MCAs) in neonatal intensive care units (NICUs) infants is challenging because of the limited diagnostic capabilities of conventional genetic tests. Although the implementation of whole genome sequencing (WGS) has commenced for diagnosing MCAs, due to constraints in resources and faculty, many NICUs continue to utilize chromosomal microarray (CMA) and/or karyotyping as the initial diagnostic approach. We aimed to evaluate the diagnostic efficacy of WGS in infants with MCAs who have received negative results from karyotyping and/or CMA. Methods: In this prospective study, we enrolled 80 infants with MCAs who were admitted to a NICU at a single center and had received negative results from CMA and/or karyotyping.The phenotypic characteristics were classified according to the International Classification of Diseases and the Human Phenotype Ontology. We assessed the diagnostic yield of trioWGS in infants with normal chromosomal result and explored the process of diagnosing by analyzing both phenotype and genotype. Also, we compared the phenotype and clinical outcomes between the groups diagnosed with WGS and the undiagnosed group. Results: The diagnostic yield of WGS was 26% (21/80), of which 76% were novel variants.There was a higher diagnostic yield in cases of craniofacial abnormalities, including those of the eye and ear, and a lower diagnostic yield in cases of gastrointestinal and genitourinary abnormalities. In addition, higher rates of rehabilitation therapy and gastrostomy were observed in WGS-diagnosed infants than in undiagnosed infants. Conclusion This prospective cohort study assessed the usefulness of trio-WGS following chromosomal analysis for diagnosing MCAs in the NICU and revealed improvements in the diagnostic yield and clinical utility of WGS.

The gastrointestinal tract is the first organ directly affected by fasting. However, little is known about how fasting influences the intestinal immune system. Intestinal dendritic cells (DCs) capture antigens, migrate to secondary lymphoid organs, and provoke adaptive immune responses. We evaluated the changes of intestinal DCs in mice with short-term fasting and their effects on protective immunity against Listeria monocytogenes(LM). Fasting induced an increased number of CD103 + CD11b − DCs in both small intestinal lamina propria (SILP) and mesenteric lymph nodes (mLN). The SILP CD103 + CD11b − DCs showed proliferation and migration, coincident with increased levels of GM-CSF and C-C chemokine receptor type 7, respectively. At 24 h post-infection with LM, there was a significant reduction in the bacterial burden in the spleen, liver, and mLN of the short-term-fasted mice compared to those fed ad libitum. Also, short-term-fasted mice showed increased survival after LM infection compared with ad libitum-fed mice. It could be that significantly high TGF-β2 and Aldh1a2 expression in CD103 + CD11b - DCs in mice infected with LM might affect to increase of Foxp3 + regulatory T cells. Changes of major subset of DCs from CD103 + to CD103 - may induce the increase of IFN-γ–producing cells with forming Th1-biased environment.Therefore, the short-term fasting affects protection against LM infection by changing major subset of intestinal DCs from tolerogenic to Th1 immunogenic.

BACKGROUND: Autophagy plays important roles in odontogenic differentiation of dental pulp cells (DPCs) in the developmental stage of tooth bud. Few studies have reported the role of autophagy during reparative dentin formation process. The objective of this study was to discover gene expression pattern correlated to autophagy and their role during odontogenic differentiation process in DPCs. METHODS: After tooth cavities were prepared on the mesial surface of lower first molar crown of rats. Odontogenic differentiation and reparative dentin formation were assessed based on detection of morphology change with hematoxylin and eosin staining. RESULTS: After tooth cavities were prepared on the mesial surface of lower first molar crown of rats, odontogenic differentiation and reparative dentin formation were assessed based on detection of morphology change with hematoxylin and eosin staining and dentin sialophosphoprotein (DSPP), whereas autophagy inhibitor 3-methyladenine (3MA) reversed. Results: of quantitative polymerized chain reaction array of autophagosome formation related genes revealed that GABARAPL2 was prominently upregulated while expression of other ATG8 family members were moderately increased after tooth cavity preparation. In addition, human DPCs incubated in differentiation medium predominantly upregulated MAP1LC3C, which selectively decreased by 3MA but not by autophagy enhancer trehalose. Knock-down of MAP1LC3C using shRNA resulted in strong downregulation of dentin matrix protein 1 and DSPP as well-known odontogenic marker compared to knock-down of MAP1LC3B during odontogenic differentiation process of human DPCs. CONCLUSION Our results suggest that MAP1LC3C plays a crucial role in odontogenic differentiation of human DPCs via regulating autophagic flux.

Background: Macrosomia, as an infant with birth weight over 4 kg, can have several perinatal, and neonatal complications. This study aimed to estimate the incidence of macrosomia in Korea and to identify the growth and developmental outcomes and other neonatal complications. Methods: In total, 397,203 infants who were born in 2013 with birth weight ≥ 2.5 kg and who underwent infant health check-up between their 1 st and 7 th visit were included from the National Health Insurance Service database. The information was obtained by the International Classification of Diseases-10 codes or self-reported questionnaires in the National Health Screening Program. Results: The distribution of infants by birth weight was as follows: 384,181 (97%) infants in the 2.5–3.99 kg (reference) group, 12,016 (3%) infants in the 4.0–4.49 kg group, 772 (0.2%) infants in the 4.5–4.99 kg group, and 78 (0.02%) infants in the ≥ 5 kg group. Macrosomia showed significantly higher incidence of sepsis, male sex, and mothers with GDM and birth injury. There was a significant difference in weight, height, and head circumference according to age, birth weight group, and combination of age and birth weight, respectively (P < 0.001). The number of infants with the weight above the 90 th percentile in macrosomia at each health check-up showed higher incidence than in reference group. The mean body mass index significantly differed among the groups, as 50.6 in infants with 2.5–3.99 kg of birth weight, 63.5 with 4.0–4.49 kg, 71.0 with 4.5–4.99 kg, and 73.1 with ≥ 5 kg. There was a significant difference in the incidence of poor developmental results between infants with macrosomia and the reference group at 24, 36 and 48 month of age. Conclusion Macrosomia was significantly associated with the risk of sepsis, birth injury, obesity and developmental problem especially in a boy born from mothers with gestational diabetes mellitus. Careful monitoring and proper strategies for monitoring growth and development are needed.

BACKGROUND: Autophagy plays important roles in odontogenic differentiation of dental pulp cells (DPCs) in the developmental stage of tooth bud. Few studies have reported the role of autophagy during reparative dentin formation process. The objective of this study was to discover gene expression pattern correlated to autophagy and their role during odontogenic differentiation process in DPCs. METHODS: After tooth cavities were prepared on the mesial surface of lower first molar crown of rats. Odontogenic differentiation and reparative dentin formation were assessed based on detection of morphology change with hematoxylin and eosin staining. RESULTS: After tooth cavities were prepared on the mesial surface of lower first molar crown of rats, odontogenic differentiation and reparative dentin formation were assessed based on detection of morphology change with hematoxylin and eosin staining and dentin sialophosphoprotein (DSPP), whereas autophagy inhibitor 3-methyladenine (3MA) reversed. Results: of quantitative polymerized chain reaction array of autophagosome formation related genes revealed that GABARAPL2 was prominently upregulated while expression of other ATG8 family members were moderately increased after tooth cavity preparation. In addition, human DPCs incubated in differentiation medium predominantly upregulated MAP1LC3C, which selectively decreased by 3MA but not by autophagy enhancer trehalose. Knock-down of MAP1LC3C using shRNA resulted in strong downregulation of dentin matrix protein 1 and DSPP as well-known odontogenic marker compared to knock-down of MAP1LC3B during odontogenic differentiation process of human DPCs. CONCLUSION Our results suggest that MAP1LC3C plays a crucial role in odontogenic differentiation of human DPCs via regulating autophagic flux.

We investigated the incidence of bronchopulmonary dysplasia (BPD) in very-low-birth-weight (VLBW) infants in Korea using the Korean Neonatal Network (KNN) data. In total, 2,386 VLBW infants born from January 2013 to June 2014 were prospectively registered. BPD was defined as supplemental oxygen or positive pressure support at 36 weeks postmenstrual age (PMA). The overall incidence of BPD was 28.9%, and the overall mortality rate in the neonatal intensive care units (NICUs) was 11.9%. To investigate recent changes in the incidence of BPD among VLBW infants, we compared the BPD rate in the present study with the latest nationwide retrospective survey conducted between 2007 and 2008. For comparison, we selected infants (23-31 weeks of gestation) (n=1,990) to adjust for the same conditions with the previous survey in 2007-2008 (n=3,841). Among the limited data on VLBW infants (23-31 weeks of gestation), the incidence of BPD increased by 85% (from 17.8% to 33.0%) and the mortality rate in the NICU decreased by 31.4% (from 18.8% to 12.9%) compared to those in the study conducted in 2007-2008. The current trend of increase in the incidence of BPD among infants can be attributed to the increase in the survival rate of VLBW infants.
Apgar Score ; Bronchopulmonary Dysplasia/*epidemiology/mortality ; Databases, Factual ; Female ; Gestational Age ; Humans ; Incidence ; Infant ; Infant Mortality ; Infant, Newborn ; *Infant, Very Low Birth Weight ; Intensive Care Units, Neonatal ; Male ; Odds Ratio ; Republic of Korea/epidemiology ; Retrospective Studies ; Risk Factors ; Survival Rate

Most of the congenital diaphragmatic hernia (CDH) cases are diagnosed at prenatal period or immediately after birth with severe respiratory symptom. The classic triad, which is respiratory distress, apparent dextrocardia and a scaphoid abdomen, is usually seen in this period. Several case reports have described older infants and children with a wide spectrum of symptoms of CDH, whereas extremely few cases were reported in neonatal period except classic triad such as straungulation of the bowel. These atypical manifestations can lead physician to delayed diagnosis. We report two cases of CDH newborns. First case was diagnosed with pneumoperitoneum following tension pneumothorax, transient diaphragm eventration on 5 days after birth. The other case was diagnosed with failure to thrive and mediastinal mass on 30 days after birth. These cases suggest physicians to consider CDH in late newborn period with pneumoperitoneum following tension pneumothorax, transient diaphragm eventration, failure to thrive, and mediastinal mass.
Abdomen ; Child ; Delayed Diagnosis ; Dextrocardia ; Diaphragmatic Eventration ; Failure to Thrive ; Hernia, Diaphragmatic* ; Humans ; Infant ; Infant, Newborn* ; Parturition ; Pneumoperitoneum ; Pneumothorax

OBJECTIVE: The aim of this study was to provide normative data on the Literacy Independent Cognitive Assessment (LICA) and to explore the effects of age, education/literacy, and gender on the performance of this test. METHODS: Eight hundred and eighty-eight healthy elderly subjects, including 164 healthy illiterate subjects, participated in this study. None of the participants had serious medical, psychiatric, or neurological disorders including dementia. Bivariate linear regression analyses were performed to examine the effects of age, education/literacy, and sex on the score in each of the LICA cognitive tests. The normative scores for each age and education/literacy groups are presented. RESULTS: Bivariate linear regression analyses revealed that total score and all cognitive tests of the LICA were significantly influenced by both age and education/literacy. Younger and more-educated subjects outperformed older and illiterate or less-educated subjects, respectively, in all of the tests. The normative scores of LICA total score and subset score were presented according to age (60-64, 65-69, 70-74, 75-80, and > or =80 years) and educational levels (illiterate, and 0-3, 4-6, and > or =7 years of education). CONCLUSION: These results on demographic variables suggest that age and education should be taken into account when attempting to accurately interpret the results of the LICA cognitive subtests. These normative data will be useful for clinical interpretations of the LICA neuropsychological battery in illiterate and literate elderly Koreans. Similar normative studies and validations of the LICA involving different ethnic groups will help to enhance the dementia diagnosis of illiterate people of different ethnicities.
Aged* ; Dementia ; Diagnosis ; Education ; Ethnic Groups ; Humans ; Linear Models ; Nervous System Diseases

PURPOSE: This study aimed to compare the neonatal outcome by quantifying the effect of maternal age on low birth weight (LBW). METHODS: We reviewed the medical records of 12,742 newborn infants born at CHA Bundang Medical Center from January 2009 to December 2013. Infants were compared after being categorized by the following 4 maternal age groups - <25 years (N=343), 25-34 years (N=8,573), 35-39 years (N=3,186), > or =40 years (N=640). Statistical analysis included use of logistic regression models with likelihood ratio tests for interaction effects. RESULTS: Incidence of perinatal complications tended to increase significantly with maternal age - gestational diabetes mellitus (GDM; P<0.001), pregnancy induced hypertension (PIH; P=0.019), placenta previa (P<0.001), and cesarean section (P<0.001). Compared to the age group of 25-34 years (reference group), no significant differences were found in age group of 35-39 year [odds ratio (OR)=0.945, 95% confidence interval (CI) 0.847-1.056, P=0.319] and > or =40 years (OR=0.841, 95% CI 0.671-1.056, P=0.136) for LBW. After adjusted by gestational age, incidence of in vitro fertilization (IVF), and perinatal complications, maternal age was not found to be an independent risk factor for LBW (OR=0.847, 95% CI 0.730-0.982, P=0.028 for 35-39 years, and OR=0.652, 95% CI 0.481-0.884, P=0.006 for > or =40 years). CONCLUSION: Although incidence of perinatal complications tends to increase with age, neonatal outcome of age group of > or =35 years measured by incidence of LBW infants was not unfavorable compared to the reference group. The result suggests that the thorough prenatal care may be more important than the maternal age itself.
Cesarean Section ; Diabetes, Gestational ; Female ; Fertilization in Vitro ; Gestational Age ; Humans ; Hypertension, Pregnancy-Induced ; Incidence ; Infant ; Infant, Low Birth Weight ; Infant, Newborn* ; Logistic Models ; Maternal Age* ; Medical Records ; Parturition* ; Placenta Previa ; Pregnancy ; Prenatal Care ; Risk Factors

PURPOSE: We evaluated the clinical characteristics of term infants admitted to the neonatal intensive care unit (NICU) from nursery. METHODS: This is a study of NICU-admitted infants who were born > or =37 weeks of gestation at the Bungdang CHA Hospital between January 2012 and August 2013 (n=161). The infants were divided into 3 groups. The "nursery room (NR) group" (n=97) comprised admissions from the nursery following a late deterioration in condition. The "delivery room (DR) group" (n=64) comprised infants who required admission to the NICU immediately after delivery. In addition, healthy term infants who were selected as the "Term group" (n=95). RESULTS: The NR group had a higher incidence of respiratory distress syndrome than DR group (28.9% vs. 14.1%, P=0.029). Compared with the Term group, the NR group had increased incidence of prolonged (>18 h) premature rupture of membranes (PROM) (6.2% vs. 0.0%, P=0.029). By logistic regression analysis, comparing NR group and Term group, a 1 min Apgar score < or =7 points {odds ratio (OR) and 95% confidence intervals (CI) 3.1 (1.0-9.1)}, a requirement of O2 at birth 2.6 (1.2-5.9) and abnormalities detected on an antenatal sonogram 3.3 (1.4-7.8) were associated with an increased risk of admission to NICU. CONCLUSION: Risk factors for NICU admission from nursery in term infants included prolonged PROM, a 1 min Apgar score of < or =7 points, a requirement of O2 at birth, and abnormalities on antenatal sonograms. Term infants with these risk factors should be carefully observed in the early neonatal period.
Apgar Score ; Humans ; Incidence ; Infant* ; Infant, Newborn ; Intensive Care, Neonatal* ; Logistic Models ; Membranes ; Nurseries* ; Parturition ; Patient Admission ; Pregnancy ; Risk Factors ; Rupture ; Term Birth