Short-term neonatal and long-term infant outcome of late-preterm twins: nationwide population-based study.

OBJECTIVES: To evaluate the short- and long-term outcome of late-preterm compared with term birth in twin pregnancy. METHODS: This retrospective observational cohort study included all women who had a twin delivery between 1 January 2007 and 31 December 2010 recorded in the claims database of the Korea National Health Insurance, with at least one follow-up recorded in the database of the National Health Screening Program for Infants and Children. Outcomes were analyzed at the pregnancy level, with adverse outcome being defined as an adverse outcome in one or both twins, identified by a diagnosis according to the International Classification of Diseases 10th Revision. The primary short-term outcome was composite morbidity, which included any of the following: transient tachypnea, respiratory distress syndrome, necrotizing enterocolitis, intraventricular hemorrhage and bronchopulmonary dysplasia. Long-term adverse outcome included any neurological or neurodevelopmental outcome, defined by prespecified neurological and developmental diagnoses; these were assessed by following up all neonates until the end of 2018, by which time they were 8-11 years of age. Outcomes were compared between twins delivered late preterm (34 + 0 to 36 + 6 weeks) and those delivered at term (≥ 37 weeks). RESULTS: Among 17 189 women who delivered twins at ≥ 34 weeks of gestation during the study period, 5032 (29.27%) women delivered in the late-preterm period. On multivariate analysis, compared with the twins delivered at term, the late-preterm twins had an increased risk for the primary short-term outcome of composite morbidity (adjusted odds ratio (aOR), 2.09; 95% CI, 1.90-2.30), including transient tachypnea (aOR, 1.85; 95% CI, 1.64-2.09), respiratory distress syndrome (aOR, 2.31; 95% CI, 2.04-2.62), necrotizing enterocolitis (aOR, 2.10; 95% CI, 1.20-3.69) and intraventricular hemorrhage (aOR, 2.13; 95% CI, 1.46-3.11). For the long-term outcome, the late-preterm twins also had an increased risk for any neurological or neurodevelopmental outcome (adjusted hazard ratio, 1.14; 95% CI, 1.07-1.21). CONCLUSIONS: Twins delivered in the late-preterm period have an increased risk for short- and long-term morbidity compared with twins delivered at term. These results should be considered when determining the timing of delivery in uncomplicated twin pregnancy. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.

Effects of sFlt-1 and alpha 2-macroglobulin on vascular endothelial growth factor-induced endothelin-1 upregulation in human microvascular endothelial cells.

INTRODUCTION: Soluble fms-like tyrosine kinase-1 (sFlt-1) is a vascular endothelial growth factor (VEGF) binding protein and potent antagonist of VEGF. Alpha 2 macroglobulin (α2M) is another major binding protein for circulating VEGF, which is present in human plasma at higher concentration (2-4 mg/mL) than sFlt-1. This study investigated the effects of sFlt-1 and α2M on VEGF-induced endothelin-1 (ET-1) upregulation in human microvascular endothelial cell-1 (HMEC-1). METHODS: HMEC-1 was cultured and incubated with varying concentrations of sFlt-1 and α2M in combination with VEGF. ET-1 mRNA expression in the cells was measured by real time RT-PCR and ET-1 protein by western blot analysis. RESULTS: ET-1 expression in HMEC-1 incubated with VEGF significantly increased in time- and dose-dependent manners. Next, HMEC-1 was treated with the sFlt-1 (10-1000 ng/mL) or α2M (10-10000 ng/mL) in the presence of VEGF (10 ng/mL). We found that sFlt-1 induced a significant decrease of ET-1 expression upregulated by VEGF, while α2M did not affect the VEGF-induced ET-1 expression. CONCLUSIONS: sFLT-1 suppressed the VEGF-induced the ET-1 expression of HMEC-1. However, α2M did not show a significant effect on the ET-1 expression that was induced by VEGF. The results suggest that a certain proportion of the bound form α2M-VEGF have a biological action involved in the pathophysiology of preeclampsia.

Monitoring of viruses in chum salmon (Oncorhynchus keta) migrating to Korea.

It is important to investigate the prevalence of salmonid pathogens because they can affect the amount of release of salmonid fry and the migration rate of adult salmonids. In this study, routine surveys were conducted for investigating virus distribution in migrating chum salmon spawners (Oncorhynchus keta) and their offsprings at the Namdae River, Yangyang, Korea, during 2006-2008. Anterior kidneys were removed from chum salmon spawner individuals, homogenized with minimal essential medium, and centrifuged to make supernatants for conducting RT-PCR. Five offspring were pooled to for conducting RT-PCR. Infectious pancreatic necrosis virus (IPNV), infectious hematopoietic necrosis virus (IHNV) and viral hemorrhagic septicemia virus (VHSV) were the target viruses for monitoring. In 2006, only spawners were investigated, and 27.5% of fish (22/80) were found to be IHNV-positive by nested PCR. In 2007, 65.6% of pooled fry (21/32) were IHNV-positive, and 9.4% (3/32) were IPNV-positive by one-step PCR. When nested PCR was conducted, 84.4% (27/32) were IHNV-positive, and 28.1% (9/32) were IPNV-positive. However, only 1.3% of spawners (1/80) were IHNV-positive by nested PCR. In 2008, 25% (8/32) of pooled fry were IHNV-positive by one-step PCR, but 59.4% (19/32) were IHNV-positive and 12.5% (4/32) were IPNV-positive by nested PCR. All of the samples tested were VHSV-negative. Although all viruses detected in this study were from chum salmon, phylogenetic analysis showed that they possibly originated from rainbow trout or clustered with the rainbow trout isolates. More extensive long-term studies are needed to clarify the origins of these viruses and their potential effects on chum salmon migration in Korea.

CUG2, a novel oncogene confers reoviral replication through Ras and p38 signaling pathway.

As we have recently found a novel oncogene, the cancer-upregulated gene 2 (CUG2), which was elevated in a variety of tumor tissues such as the ovary, liver, lung and pancreas, we examined whether reovirus could efficiently induce cytolysis in cancer cells expressing CUG2 and thus be used as a potential cancer therapeutic agent. In this study, we describe experiments in which we use reovirus to treat NIH3T3 cells stably expressing either CUG2 (NIH-CUG2) or vector only (NIH-Vec). NIH-CUG2 cells readily support reoviral proliferation and undergo apoptosis, whereas NIH-Vec cells are highly resistant to reoviral infection and virus-induced apoptosis. This notable result may be explained by the observation that CUG2 expression inhibits PKR activation, leading to reoviral proliferation in nonpermissive NIH3T3 cells. Furthermore, reovirus infection results in almost complete regression of tumorgenic NIH-CUG2 cells in transplanted nude mice. As we found that CUG2 enhances activation of MAPK (ERK, JNK and p38), Src kinase and Ras, we examined whether CUG2 confers reoviral replication independent of the Ras or p38 MAPK signaling pathway. From these experiments we found that either inhibition of p38 MAPK or Ras blocks reoviral proliferation even in the presence of CUG2 but inhibition of ERK, JNK and Src kinase does not, indicating that activation of p38 MAPK and Ras has critical roles in reoviral replication in CUG2-expressing tumor cells. Accordingly, we propose that reovirus can be useful in the treatment of transformed cells expressing CUG2, which is commonly detected in various tumor tissues.

Tunic morphology and viral surveillance in diseased Korean ascidians: Soft tunic syndrome in the edible ascidian, Halocynthia roretzi (Drasche), in aquaculture.

'Soft tunic syndrome' causes mass mortality in the edible ascidian Halocynthia roretzi in Korean and Japanese aquaculture. In histopathological comparison, there were no specific differences between diseased specimens from Korea and Japan, indicating that soft tunic syndrome occurring in Korea and Japan is the same disease. No bacterial or protozoan cells were microscopically detected in either healthy or diseased tunics suggesting they are not the direct causes of soft tunic syndrome. Attempts were made to isolate virus from affected ascidians taking into account temperature conditions in which soft tunic syndrome is most prevalent in the field. However, no viruses were isolated from diseased or non-diseased specimens using chinook salmon embryo (CHSE-214), flounder fin (FFN) or epithelioma papillosum cyprini (EPC) cell lines.

A map of relationships between uterine natural killer cells and progesterone receptor expressing cells during mouse pregnancy.

Uterine natural killer (uNK) cells appear in implantation sites with decidualization. Initially, they are rare, highly proliferative cells that become abundant by midgestation and then die abruptly. Steps regulating the cyclic appearance of uNK cells are incompletely defined. Although progesterone (P4) has an essential role, mature uNK cells of women and mice lack progesterone receptors (PR). Immunohistochemical studies suggest that mouse PR(-) uNK cells may co-localize with PR(+) stromal cells while human PR(-) uNK cells co-localize with immature, DC-SIGN(+) dendritic cells (DCs). DCs have the potential to produce progesterone-regulated interleukin (IL)-15, a growth factor essential for uNK cells. Since the high affinity IL-15Ralpha is presented to differentiating NK cells in trans, requiring cell contact, histologically-detected interactions may be of central importance for uNK cell differentiation. Thus, a pregnancy time course, histological study of uNK cell differentiation and localization was undertaken in PR(lacZ) transgenic mice. PR(+) cells and uNK cells were co-localized using LacZ histochemistry and Dolichos biflorus (DBA) lectin staining, respectively. uNK cells appeared mesometrially, where PR(+) cells were rare, at gestation day 5.5. uNK cells had limited, apparently random contact with PR(+) cells throughout pregnancy and never themselves expressed PR. Thus, uNK cell differentiation does not appear to require contact with PR(+) cells.

Uterine NK cells in murine pregnancy.

Murine uterine natural killer (uNK) cells are transient, short-lived, terminally differentiated lymphocytes found in decidualized endometrium. Cells expressing natural killer cell surface markers are present in uteri of infant mice. Terminal uNK cell differentiation coincides with mesometrial decidual development subsequent to blastocyst implantation and begins about gestation day 5. uNK cells proliferate rapidly and, within 3 days, senescent uNK cells appear in normal implantation sites. Mid-gestation, senescent cells become dominant and uNK cell numbers decline until term when remaining cells are shed with the placenta. Transplantable uNK cell progenitors occur outside the uterus, suggesting that blood cell homing augments any in-utero progenitors. Early in healthy pregnancies, uNK cells produce cytokines and angiogenic molecules. Their lytic capacity in normal gestation and in pregnancy failure is incompletely defined. A significant shift recently occurred in thinking about major uNK cell functions. Activated uNK cells are now considered critical for appropriate endometrial angiogenesis in early implantation site development and in non-gestational endometrium. Because analogous cells appear in the endometria of women during each menstrual cycle and become abundant in early pregnancy, studies involving experimental pregnancy termination in genetically manipulated mice continue to have great importance for understanding regulation at the human maternal-fetal interface.

Genotyping of Korean isolates of infectious hematopoietic necrosis virus (IHNV) based on the glycoprotein gene.

Glycoprotein (G) gene nucleotide sequences of four Korean isolates of infectious hematopoietic necrosis virus (IHNV) were analyzed to evaluate their genetic relatedness to worldwide isolates. All Korean isolates were closely related to Japanese isolates of genogroup JRt rather than to those of North American and European genogroups. It is believed that Korean IHNV has been most likely introduced from Japan to Korea by the movement of contaminated fish eggs. Among the Korean isolates, phylogenetically distinct virus types were obtained from sites north and south of a large mountain range, suggesting the possibility of more than one introduction of virus from Japan.

Risk factors for the progression or persistence of untreated mild dysplasia of the uterine cervix.

To identify the factors that may predict the progression or persistence of untreated mild dysplasia of the uterine cervix, we performed a retrospective review of 118 patients with histologically verified mild dysplasia who underwent colposcopic biopsies between January 1999 and December 2003. Regression to normal occurred in 70.3%, progression to moderate dysplasia or worse occurred in 11.0%, and persistence of mild dysplasia occurred in 18.7%. In regression/progression analysis, progression of untreated mild dysplasia was 34.5% (10/29) in patients with high viral loads (> or =100 relative light units/positive control [RLU/PC]) and 4.5% (3/67) in those with low viral loads (1 to <100 RLU/PC) and negative human papillomavirus (HPV) tests (P < 0.001). Women with high viral loads had a 13-fold greater chance of progression of untreated mild dysplasia than those with low viral loads and negative HPV tests (CI: 2.494-95.297; P = 0.0022). Those associated with both positive smear and positive HPV test (12/45 = 26.7%) were at a greater risk of progression of untreated mild dysplasia as compared with those with positive smear and negative HPV (0/17 = 0.0%) or those with negative smear and positive HPV test (1/18 = 5.6%). Those with high viral loads and both with positive smear and positive HPV test should be followed closely because of their increased risk of progression of untreated mild dysplasia.

Detection of epidermal growth factor receptor in the serum of patients with cervical carcinoma.

Epidermal growth factor receptor (EGFR) is overexpressed in a variety of malignancies, including breast, lung, gastric, and cervical carcinoma. Its overexpression has been associated with disease progression or poor prognosis in patients with cervical carcinoma. In the present study, the levels of EGFR were determined in serum from 38 patients with cervical carcinoma [invasive or recurrent carcinoma (n = 26) and carcinoma in situ (CIS; n = 12)] and 38 healthy female controls using ELISA. The mean serum level for EGFR in patients with invasive or recurrent carcinoma (165 +/- 60 fmol/ml) was significantly elevated (P < 0.0001) compared with that of healthy controls (66 +/- 17 fmol/ml) and also higher (P = 0.015) than that of patients with CIS (126 +/- 25 fmol/ml). In addition, there was a significant difference in the mean serum levels of EGFR between patients with CIS and healthy controls (P < 0.0001). Thirty-five patients (92%) with cervical carcinoma [invasive or recurrent (n = 24) and CIS (n = 11)] had elevated serum, EGFR levels above the cutoff value of 100 fmol/ml (defined as 2 SD above the mean of the controls). In conclusion, the serum EGFR level was elevated in a significant proportion of patients with cervical carcinoma, and it demonstrated an increasing tendency according to disease progression from normal tissue through CIS to invasive cervical carcinoma. Therefore, it may have a potential usefulness as a biological marker of cervical carcinoma.

Distribution of genotypes in the 5' untranslated region of hepatitis C virus in Korea.

Hepatitis C virus (HCV) is an important human pathogen that can cause acute and chronic hepatitis, liver cirrhosis and hepatocellular carcinoma. Recently, partial and entire sequence data from HCV isolates have been reported, suggesting various genotypes of HCV. The genotype may be correlated with the progression of hepatitis and maybe a prognostic marker of treatment. Thus, the availability of an assay for typing HCV RNA is important. This study developed a convenient method for genotyping HCV into six groups by PCR-RFLP with four restriction endonucleases (BstUI, HaeIII, NciI, RsaI) in the 5' untranslated region (UTR) of HCV. The HCV genotypes from 169 patients with HCV infections in Korea were analysed. Two genotypes, type 1b and type 2a, accounted for 47.3% and 42.6% of HCV infections, respectively.

Deletions of 9p21 and TP53 in bladder cancer.

The objective of this study was to characterize the alterations of 9p21 and TP53 in Korean transitional bladder cancer and to assess the relationship between the histopathologic parameter and the alteration of these genes. Allele loss in 29 surgically resected transitional cell carcinoma was examined by using the multiplex PCR with 7 and 1 microsatellite markers for 9p21 and TP53, respectively. Twenty-one (72%) demonstrated allele loss at 9p21 and/or TP53. Deletion at the 9p21 region was detected in 17(61%) of 28 informative cases at one or more loci, and LOH at TP53 was found in 12(55%) of 22 informative cases. Of 7 microsatellite markers for 9p21, allele loss occurred the most frequently at locus D9S162(69%) and D9S104(69%). Additionally, hemizygous deletion was slightly more common than homozygous deletion. Deletion at 9p21 and TP53 was not related with increased grade. These results suggest that the alteration of 9p21 may be an early event in the development of Korean bladder cancer, while p53 gene may be involved in early event of some bladder cancers as well as in their late events.