Neurodevelopmental Outcomes and Brain Volumetric Analysis of Low-Grade Intraventricular Hemorrhage

Purpose Extremely preterm infants are prone to brain injury and underdevelopment. Intraventricular hemorrhage (IVH) is the most common cause of brain injury and a significant risk factor for neurodevelopmental delay in preterm infants. Severe IVH is known to have a poor outcome; however, the outcomes of low-grade IVH remain controversial. This study aimed to evaluate neurodevelopmental outcomes and brain segmental volumes of preterm infants with low-grade IVH. Methods This retrospective cohort study included 109 extremely preterm infants who underwent term equivalent age-magnetic resonance imaging and neurodevelopmental evaluation at a corrected age of 18 to 24 months. We compared infants with and without low-grade IVH. Results Among the 109 extremely preterm infants, 25 had low-grade IVH and 84 had no IVH. There were no significant differences in the neurodevelopmental outcomes between the low-grade and no IVH groups. In multivariate analysis, low-grade IVH was associated with a smaller medullary volume (adjusted odds ratio, 0.575; 95% confidence interval, 0.346 to 0.957; P=0.034). Conclusion We found no significant differences in the neurodevelopmental outcomes of extremely preterm infants at a corrected age of 18 to 24 months between those with low-grade IVH and those without IVH. Low-grade IVH was associated with a smaller medullary volume

Contribution of actin filaments and microtubules to cell elongation and alignment depends on the grating depth of microgratings

Additional file 1: Figure S1. (A) A phase contrast image of TCPS surface. Bar, 100 μm. (B) An imageshowing FN-lines (1 μm line and spacing) obtained by Atomic Force Microscopy (AFM) (Dimension 3100with a Nanoscope III controller, Digital Instruments) using silicon cantilevers (spring constant; 50 Nm-1)(RTESP, Veeco Probes) in contact mode. (C-E) SEM (Scanning electron microscopy) (6010 LV, JEOL)images showing the cross section of three different microgratings; 1 μm gratings with 0.35 um depth (C) and1 μm depth (D) and 2 μm gratings with 2 μm depth (E). Figure S2. (A) Fluorescence image of a RPE-1 cell stably expressing GFP/centrin cell on 1 μm gratings (1 μm deep). Bar, 30 μm. A yellow arrow indicates the direction of cell elongation. (B) Average cell aspect ratio (R) of cells on 1 μm gratings (0.35 or 1 μm deep) and 2 μm gratings with/without CD treatment. n: number of cells. ***P < 0.001. Data were analyzed using one-way ANOVA and a Bonferroni post hoc test. Error bar denotes the standard deviation of the mean. Figure S3. Alignment of actin and vinculin to the different substrates (Flat TCPS surface, FN-lines, and 1 μm gratings (0.35 or 1μm deep)). The alignment angle was measured as an angle difference of actin or vinculin orientation to the long axis of a cell on flat PDMS surface or the long axis of the FN-line or each micrograting. #: the number of cells. Error bar denotes the standard deviation of the mean. Figure S4. Merged image of MTs (Green fluorescence) and pattern (phase contrast) of cells on 1 μm grating (1 μm deep) in the presenceof CD at 1 μM

Efficacy and safety of mucous fistula refeeding in preterm infants: an exploratory randomized controlled trial

Background This study aimed to evaluate whether mucous fistula refeeding (MFR) is safe and beneficial for the growth and intestinal adaptation of preterm infants with enterostomies. Methods This exploratory randomized controlled trial enrolled infants born before 35weeks gestation with enterostomy. If the stomal output was ≥ 40mL/kg/day, infants were assigned to the high-output MFR group and received MFR. If the stoma output was < 40mL/kg/day, infants were randomized to the normal-output MFR group or the control group. Growth, serum citrulline levels, and bowel diameter in loopograms were compared. The safety of MFR was evaluated. Results Twenty infants were included. The growth rate increased considerably, and the colon diameter was significantly larger after MFR. However, the citrulline levels did not significantly differ between the normal-output MFR and the control group. One case of bowel perforation occurred during the manual reduction for stoma prolapse. Although the association with MFR was unclear, two cases of culture-proven sepsis during MFR were noted. Conclusions MFR benefits the growth and intestinal adaptation of preterm infants with enterostomy and can be safely implemented with a standardized protocol. However, infectious complications need to be investigated further. Trial registration clinicaltrials.gov NCT02812095, retrospectively registered on June 6, 2016.This study was supported by Research Resettlement Fund for the new faculty of Seoul National University and Research Fund of Seoul National University Hospital (3020200170)

Regulation of mouse steroidogenesis by WHISTLE and JMJD1C through histone methylation balance

The dynamic exchange of histone lysine methylation status by histone methyltransferases and demethylases has been previously implicated as an important factor in chromatin structure and transcriptional regulation. Using immunoaffinity TAP analysis, we purified the WHISTLE-interacting protein complexes, which include the heat shock protein HSP90α and the jumonji C-domain harboring the histone demethylase JMJD1C. In this study, we demonstrate that JMJD1C specifically demethylates histone H3K9 mono- and di-methylation, and mediates transcriptional activation. We also provide evidence suggesting that both WHISTLE and JMJD1C performs functions in the development of mouse testes by regulating the expression of the steroidogenesis marker, p450c17, via SF-1-mediated transcription. Furthermore, we demonstrate that WHISTLE is recruited to the p450c17 promoter via SF-1 and represses the transcription of prepubertal stages of steroidogenesis, after which JMJD1C replaces WHISTLE and activates the expression of target genes via SF-1-mediated interactions. Our results demonstrate that the histone methylation balance mediated by HMTase WHISTLE and demethylase JMJD1C perform a transcriptional regulatory function in mouse testis development

Trends in Epidemiology of Neonatal Sepsis in a Tertiary Center in Korea: A 26-Year Longitudinal Analysis, 1980-2005

There were many reports of longitudinal changes in the causative organisms of neonatal sepsis in Western countries but few in Asia. We aimed to study longitudinal trends in the epidemiology of neonatal sepsis at Seoul National University Children's Hospital (SNUCH), a tertiary center in Korea, and compared the results to previous studies of Western countries. The medical records of all of the neonates who were hospitalized at SNUCH from 1996 to 2005 with positive blood cultures were reviewed. We also compared the findings to previous 16-yr (1980-1995). One hundred and forty-nine organisms were identified in 147 episodes from 134 infants. In comparison with the previous 16-yr studies, there was a decrease in the number of Escherichia coli infections (16.2% vs 8.7%: odds ratio [OR] 0.495; 95% confidence interval [CI], 0.255-0.962; P = 0.035), but an increase in Staphylococcus aureus (16.6% vs 25.5%: OR 1.720; 95% CI, 1.043-2.839; P = 0.033) and fungal infections (3.3% vs 18.7%: OR 6.740; 95% CI, 2.981-15.239; P < 0.001), predominantly caused by Candida species. In conclusion, the incidence of sepsis caused by E. coli decreases, but S. aureus and fungal sepsis increases significantly. Compared with Western studies, the incidence of sepsis caused by S. aureus and fungus has remarkably increased

An Antinuclear Antibody-Negative Patient With Lupus Nephritis

Systemic lupus erythematosus (SLE) is a typical autoimmune disease that's characterized by various autoantibodies to nuclear and cytoplasmic antigens. The presence of antinuclear antibodies (ANA) in serum is generally considered a decisive diagnostic sign of SLE. However, a small subset of SLE patients who had the typical clinical features of SLE was reported to show persistently negative ANA tests. Our report describes a 16-yr-old female who presented with the clinical manifestations of SLE such as malar rash, photosensitivity, arthritis, lymphopenia, pericarditis and proteinuria. The serum autoantibodies were all negative and renal biopsy showed that the histopathological changes of immune complex mediated the focal segmental necrotizing glomerulonephritis with crescent formation. She was treated with monthly pulse cyclophosphamide along with corticosteroids. During the 2-yr follow-up period, the proteinuria was markedly decreased and all of the ANA and anti-double stranded DNA antibody tests were negative. This case suggests that ANA may not be required in the pathogenesis of lupus nephritis

Survival Rate Changes in Neonates with Congenital Diaphragmatic Hernia and its Contributing Factors

The purpose of this study was to demonstrate survival rate changes after the introduction of inhaled nitric oxide (iNO) therapy, and to identify the factors that influence these changes in neonates with a congenital diaphragmatic hernia (CDH) at a single center. A total of 48 neonates were divided into two groups based on the time of admission, i.e., into period I (P1; n=17; before the introduction of iNO therapy) and period II (P2; n=31; after the introduction of iNO therapy). Survival rates of the 48 neonates showed a tendency to increase from 53% during P1 to 77% during P2, but without a statistical significance, but a significant difference was found between survival rates during the two periods after adjusting for initial clinical characteristics, when the postoperative survival rate increased significantly from 69% for P1 to 100% for P2. The mean duration of preoperative respiratory management was significantly longer for P2 than for P1. Seven of 12 patients who received preoperative iNO therapy due to persistent pulmonary hypertension or refractory preductal hypoxemia in P2 survived after operation. We speculate that a management strategy based on iNO therapy and delayed operation, rather than differences between the initial clinical characteristics of the two study groups, might partially contribute to the observed improvements in postoperative and overall survival rates in neonates with CDH

Risk Factors for Periventricular-Intraventricular Hemorrhage in Premature Infants

Periventricular-intraventricular hemorrhage (PV-IVH) is a major cause of neurological disabilities in preterm newborns. This study aimed to determine the perinatal factors associated with PV-IVH. We conducted a retrospective case-control study from preterm infants born at ≤34 weeks of gestation and admitted to Neonatal Intensive Care Units of Seoul National University Children's Hospital and Seoul National University Bundang Hospital between June 2003 and December 2007. Neonates with no cranial sonographic data or infants transferred from other centers after three days of age were excluded. Of 1,044 eligible subjects, 59 infants with PV-IVH grade 2, 3, and 4 were allocated to the case group. The control group consisted of 118 infants without PV-IVH who were matched for gestational age and birth weight to each case of PV-IVH. At the multivariate logistic regression model, metabolic acidosis (odds ratio [OR]: 6.94; 95% confidence interval [CI]: 1.12-43.23) and use of inotropes (OR: 3.70; 95% CI: 1.16-11.84) were associated with an increased risk of PV-IVH. Maternal use of antenatal corticosteroids decreases the risk of PV-IVH (OR: 0.36; 95% CI: 0.14-0.92)

Clinical Presentations and Neurodevelopmental Outcomes of Perinatal Stroke in Preterm and Term Neonates: A Case Series

Perinatal stroke in neonates can lead to disability in later life. However, its etiology and prognosis are poorly understood. The aim of this study was to describe clinical presentations and neurodevelopmental outcomes of our case series of perinatal stroke in Korea. Thirteen term and preterm neonates who were diagnosed with perinatal stroke in two university hospitals from March 2003 to March 2007 were enrolled. Seven term and 6 preterm neonates were diagnosed with perinatal stroke, based on the brain MRI findings. Perinatal stroke presented with seizure (4/13), perinatal distress (3/13) in term neonates, whereas stroke in preterm neonates did not present with noticeable clinical symptoms. Only one neonate had positive thrombophilic test (homozygous C677T polymorphism for MTHFR). Ten neonates had infarctions in the territory of the middle cerebral artery (MCA), and 3 neonates had borderzone infarctions between the anterior cerebral artery and MCA. Neurodevelopmental outcome was abnormal in 4 neonates. Infarction in MCA main branch or posterior limb of internal capsule showed an abnormal neurodevelopmental outcome. Our study is the first systematic study of perinatal stroke in Korea, and shows its clinical presentations and neurodevelopmental outcomes. The population-based study on incidence and prognosis of perinatal stroke in Korea is required in the future