Differential Expression of NME4 in Trophoblast Stem-Like Cells and Peripheral Blood Mononuclear Cells of Normal Pregnancy and Preeclampsia

Background@#Preeclampsia (PE) is known to arise from insufficient trophoblast invasion as uterine spiral arteries lack remodeling. A significant reduction in placental perfusion induces an ischemic placental microenvironment due to reduced oxygen delivery to the placenta and fetus, leading to oxidative stress. Mitochondria are involved in the regulation of cellular metabolism and the production of reactive oxygen species (ROS). NME/NM23 nuceloside diphosphate kinase 4 (NME4) gene is known to have the ability to supply nucleotide triphosphate and deoxynucleotide triphosphate for replication and transcription of mitochondria. Our study aimed to investigate changes in NME4 expression in PE using trophoblast stem-like cells (TSLCs) from induced pluripotent stem cells (iPSCs) as a model of early pregnancy and peripheral blood mononuclear cells (PBMNCs) as a model of late preterm pregnancy. @*Methods@#Transcriptome analysis using TSLCs was performed to identify the candidate gene associated with the possible pathophysiology of PE. Then, the expression of NME4 associated with mitochondrial function, p53 associated with cell death, and thioredoxin (TRX) linked to ROS were investigated through qRT-PCR, western blotting and deoxynucleotidyl transferase (TdT)-mediated deoxyuridine triphosphate (dUTP) nick end labelling (TUNEL) assay. @*Results@#In patients with PE, NME4 was significantly downregulated in TSLCs but upregulated in PBMNCs. p53 was shown to be upregulated in TSLCs and PBMNCs of PE. In addition, western blot analysis confirmed that TRX expression had the tendency to increase in TSLCs of PE. Similarly, TUNEL analysis confirmed that the dead cells were higher in PE than in normal pregnancy. @*Conclusion@#Our study showed that the expression of the NME4 differed between models of early and late preterm pregnancy of PE, and suggests that this expression pattern may be a potential biomarker for early diagnosis of PE.

6-O-Galloylsalidroside, an Active Ingredient from Acer tegmentosum, Ameliorates Alcoholic Steatosis and Liver Injury in a Mouse Model of Chronic Ethanol Consumption

We have previously reported that Acer tegmentosum extract, which is traditionally used in Korea to reduce alcohol-related liver injury, suppresses liver inflammation caused by excessive alcohol consumption and might improve metabolism. The active ingredient, 6-O-galloylsalidroside (GAL), was isolated from A.tegmentosum, and we hypothesized that GAL could provide desirable pharmacological benefits by ameliorating physiological conditions caused by alcohol abuse. Therefore, this study focused on whether GAL could ameliorate alcoholic fat accumulation and repair liver injury in mice. During chronic alcohol consumption plus binge feeding in mice, GAL was administered orally once per day for 11 days. Intrahepatic lipid accumulation was measured in vivo using a noninvasive method, 1H magnetic resonance imaging, and confirmed by staining with hematoxylin and eosin and Oil Red O. The serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were measured using a Konelab system, and the triglyceride content was measured in liver homogenates using an enzymatic peroxide assay. The results suggested that GAL alleviated alcohol-induced steatosis,e as indicated by decreased hepatic and serum triglyceride levels in ethanol-fed mice. GAL treatment also correlated with a decrease in the Cd36 mRNA expression, thus potentially inhibiting the development of alcoholic steatosis via the hepatic de novo lipogenesis pathway. Furthermore, treatment with GAL inhibited the expression of cytochrome P450 2E1 and attenuated hepatocellular damage, as reflected by a reduction in ALT and AST levels. These findings suggest that GAL extracted from A.tegmentosum has the potential to serve as a bioactive agent for the treatment of alcoholic fatty liver and liver damage.

6-O-Galloylsalidroside, an Active Ingredient from Acer tegmentosum, Ameliorates Alcoholic Steatosis and Liver Injury in a Mouse Model of Chronic Ethanol Consumption

We have previously reported that Acer tegmentosum extract, which is traditionally used in Korea to reduce alcohol-related liver injury, suppresses liver inflammation caused by excessive alcohol consumption and might improve metabolism. The active ingredient, 6-O-galloylsalidroside (GAL), was isolated from A.tegmentosum, and we hypothesized that GAL could provide desirable pharmacological benefits by ameliorating physiological conditions caused by alcohol abuse. Therefore, this study focused on whether GAL could ameliorate alcoholic fat accumulation and repair liver injury in mice. During chronic alcohol consumption plus binge feeding in mice, GAL was administered orally once per day for 11 days. Intrahepatic lipid accumulation was measured in vivo using a noninvasive method, 1H magnetic resonance imaging, and confirmed by staining with hematoxylin and eosin and Oil Red O. The serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were measured using a Konelab system, and the triglyceride content was measured in liver homogenates using an enzymatic peroxide assay. The results suggested that GAL alleviated alcohol-induced steatosis,e as indicated by decreased hepatic and serum triglyceride levels in ethanol-fed mice. GAL treatment also correlated with a decrease in the Cd36 mRNA expression, thus potentially inhibiting the development of alcoholic steatosis via the hepatic de novo lipogenesis pathway. Furthermore, treatment with GAL inhibited the expression of cytochrome P450 2E1 and attenuated hepatocellular damage, as reflected by a reduction in ALT and AST levels. These findings suggest that GAL extracted from A.tegmentosum has the potential to serve as a bioactive agent for the treatment of alcoholic fatty liver and liver damage.

High-risk human papillomavirus testing as a primary screening for cervical cancer: position statement by the Korean Society of Obstetrics and Gynecology and the Korean Society of Gynecologic Oncology

Based on emerging data and current knowledge regarding high-risk human papillomavirus (hrHPV) testing as a primary screening for cervical cancer, the Korean Society of Obstetrics and Gynecology and the Korean Society of Gynecologic Oncology support the following scientific facts: • Compared to cytology, hrHPV screening has higher sensitivity and detects more cases of high-grade cervical intraepithelial neoplasia. • Qualified hrHPV testing can be considered as an alternative primary screening for cervical cancer to the current cytology method. • The starting age of primary hrHPV screening should not be before 25 years because of possible overtreatment in this age, which has a high human papillomavirus (HPV) prevalence but rarely progresses to cancer. The screening interval should be no sooner than every 3 years and no longer than every 5 years. • Before the introduction of hrHPV screening in Korea, research into comparative effectiveness of primary hrHPV screening for cervical cancer should be conducted to determine the appropriate HPV assay, starting age, and screening interval.

High-risk human papillomavirus testing as a primary screening for cervical cancer: position statement by the Korean Society of Obstetrics and Gynecology and the Korean Society of Gynecologic Oncology / 부인종양

Based on emerging data and current knowledge regarding high-risk human papillomavirus (hrHPV) testing as a primary screening for cervical cancer, the Korean Society of Obstetrics and Gynecology and the Korean Society of Gynecologic Oncology support the following scientific facts:• Compared to cytology, hrHPV screening has higher sensitivity and detects more cases of high-grade cervical intraepithelial neoplasia.• Qualified hrHPV testing can be considered as an alternative primary screening for cervical cancer to the current cytology method.• The starting age of primary hrHPV screening should not be before 25 years because of possible overtreatment in this age, which has a high human papillomavirus (HPV) prevalence but rarely progresses to cancer. The screening interval should be no sooner than every 3 years and no longer than every 5 years.• Before the introduction of hrHPV screening in Korea, research into comparative effectiveness of primary hrHPV screening for cervical cancer should be conducted to determine the appropriate HPV assay, starting age, and screening interval.

Superior Mesenteric Venous Thrombophlebitis with Terminal Ileal Diverticulitis: A Case Report

Mesenteric venous thrombophlebitis secondary to inflammatory processes such as diverticulitis and appendicitis is a rare disease; however, it can nonetheless cause bowel ischemia and infarctions. Radiologic diagnosis is vital for mesenteric venous thrombophlebitis complicated with diverticulitis due to its non-specific clinical presentation and very low incidence. We report a case of a 61-year-old woman with superior mesenteric vein thrombosis and ileocecal diverticulitis on CT, which was resolved after treatment with a combination of antibiotic therapy and right hemicolectomy.

High-risk human papillomavirus testing as a primary screening for cervical cancer: position statement by the Korean Society of Obstetrics and Gynecology and the Korean Society of Gynecologic Oncology / 부인종양

Persicaria senticosa Ameliorates Imiquimod-induced Psoriasis-like Skin Lesions in Mice via Suppression of IL-6/STAT3 Expression and Proliferation of Keratinocytes

Psoriasis is one of the most common inflammatory skin disorders, with a global prevalence of 2% – 3%. It is an autoimmune skin disorder characterized by excessive generation of plaques on the skin with typical long-lasting red, itchy, and scaly lesions. In this study, we aimed to elucidate the anti-psoriatic effect of the methanolic extract of Persicaria senticosa (PS), a bioactive edible plant extract used in traditional medicine, using a mouse model of imiquimod (IMQ)-induced psoriasis. The daily topical application of IMQ could induce human psoriasis-like lesion. The extract ameliorated IMQ-induced psoriasis. Furthermore, hematoxylin and eosin staining and the Psoriasis Area and Severity Index (PASI) scores indicated that topical application of PS led to an improvement in erythema, scaling, and thickness scores of the mouse dorsal skin and a considerable decrease in the epidermal thickness of the ear and dorsal skin in the IMQ-induced psoriatic mouse model. We also studied the effect of PS on the proliferation of keratinocytes using HaCaT cells. The extract inhibited cell proliferation and IL-6 and pSTAT3 expression induced by M5 cocktail (comprising interleukin [IL]-1α, IL-17A, IL-22, oncostatin M, and tumor necrosis factor-α) in HaCaT cells. Thus, PS might serve as a potential therapeutic agent for the treatment of psoriasis.

Cesarean section does not increase the prevalence of allergic disease within 3 years of age in the offsprings

OBJECTIVE: In this study, we evaluated the prevalence of allergic disease in offsprings delivered via the delivery modes of vaginal delivery vs. planned Cesarean section vs. Cesarean section with labor. METHODS: This study included 175 mother-neonate pairs from Severance Hospital who were enrolled in the Cohort for Childhood Origin of Asthma and allergic diseases study. Information regarding prenatal environmental factors, delivery, and diagnosis of allergic diseases was obtained from a questionnaire and medical record review. Patients with at least 3 years of follow-up data were included in this study. Results were adjusted for sex, birth weight, gestational age at birth, season of birth, neonatal intensive care unit admission, parity, breastfeeding, and maternal factors. RESULTS: A total of 175 offsprings were eligible for analysis. Among the subjects, 52.0% were delivered by vaginal delivery, 34.3% by planned Cesarean section, and 16.6% by Cesarean section with labor. Fifty-nine offsprings (33.7%) were diagnosed with allergic disease at a median age of 1 year (range 0.5–3 years). The prevalence of allergic disease was not associated with delivery mode after adjusting for confounding variables. Time period from membrane rupture to delivery, duration of the active phase, and the beginning of the pelvic division prior to Cesarean section were not associated with allergic disease development in offsprings. CONCLUSION: Cesarean section, irrespective of the occurrence of labor before surgery, did not increase the prevalence of allergic disease in infants up to 3 years of age.

Reliability of society of fetal urology and Onen grading system in fetal hydronephrosis

OBJECTIVE: To evaluate the reliability of the Society for Fetal Urology (SFU) and Onen grading systems for fetal hydronephrosis in prenatal ultrasound according to the level of experience of the examiner. METHODS: We reviewed the prenatal ultrasound images of 146 fetuses (292 kidneys) that were diagnosed as having hydronephrosis between January 2005 and December 2014. One expert and two trainees assessed the prenatal renal ultrasound images using the SFU and Onen grading systems. The three examiners independently assessed each ultrasound image with both grading systems and reassessed the same images after 7 to 14 days. Cohen's kappa statistic was used to estimate intra- and inter-observer reliability in prenatal ultrasound images according to training level. RESULTS: The intra-observer reliability of the SFU grading system (κ 0.873–0.945) showed almost perfect agreement and that of the Onen grading system (κ 0.749–0.913) showed substantial to almost perfect agreement. The overall inter-observer reliability of the SFU grading system (κ 0.620–0.825) showed substantial to almost perfect agreement and that of the Onen grading system (κ 0.618–0.724) showed substantial agreement. The weighted kappa value of inter-observer agreement was 0.223 to 0.400 for SFU grade 1 and 0.064 to 0.346 for SFU grade 3. For Onen grading, the inter-observer agreement was 0.012 to 0.214 for grade 2 and 0.193 to 0.334 for grade 3. CONCLUSION: Both the SFU and Onen grading systems showed good intra-observer agreement in prenatal ultrasonography. The inter-observer agreement was decreased in SFU grades 1 and 3 and Onen grades 2 and 3. Therefore, more focus should be given to SFU grades 1 and 3 and Onen grades 2 and 3 for trainees.

Erratum: Correction of the name of society

The name of society was published incorrectly.

Bilateral salpingectomy to reduce the risk of ovarian/fallopian/peritoneal cancer in women at average risk: a position statement of the Korean Society of Obstetrics and Gynecology (KSOG)

Based on the current understanding of a preventive effect of bilateral salpingectomy on ovarian/fallopian/peritoneal cancers, the Korean Society of Obstetrics and Gynecology, Korean Society of Gynecologic Endocrinology, Korean Society of Gynecologic Oncology, Korean Society of Maternal Fetal Medicine, and Korean Society for Reproductive Medicine support the following recommendations:• Women scheduled for hysterectomy for benign gynecologic disease should be informed that bilateral salpingectomy reduces the risk of ovarian/fallopian/peritoneal cancer, and they should be counseled regarding this procedure at the time of hysterectomy.• Although salpingectomy is generally considered as a safe procedure in terms of preserving ovarian reserve, there is a lack of evidences representing its long-term outcomes. Therefore, patients should be informed about the minimal potential of this procedure for decreasing ovarian reserve.• Prophylactic salpingectomy during vaginal hysterectomy is favorable in terms of prevention of ovarian/fallopian/peritoneal cancer, although operation-related complications minimally increase with this procedure, compared to the complications associated with vaginal hysterectomy alone. Conversion to open or laparoscopic approach from vaginal approach to perform prophylactic salpingectomy is not recommended.• Women who desire permanent sterilization at the time of cesarean delivery could be counseled for prophylactic salpingectomy before surgery on an individual basis.

Preeclampsia Increases the Incidence of Postpartum Cerebrovascular Disease in Korean Population

BACKGROUND: Multiple studies have been reported regarding preeclampsia as a possible risk factor of cerebrovascular disease (CVD). However, the correlation of preeclampsia and CVD, whether it is a cause-effect relationship or they are sharing common predisposing condition, is not well understood. Therefore, the aim of this study was to investigate the association between the preeclampsia during pregnancy and development of postpartum CVD. METHODS: A total of 1,384,550 Korean women who had a delivery between January 1, 2010 and December 31, 2012, were enrolled. Women with the risk of CVD within 1 year prior to pregnancy were excluded based on the Charlson comorbidity index. Primary endpoint was the event of CVD within a year from delivery. After exclusion, 1,075,061 women were analyzed. RESULTS: During the follow-up of 1 year postpartum, there were 25,577 preeclampsia out of 1,072,041 women without postpartum CVD (2.39%), and 121 of 3,020 women with postpartum CVD had preeclampsia before delivery (4.01%). In multivariate logistic regression analysis, women who had preeclampsia during pregnancy showed a higher risk for postpartum CVD (odds ratio, 1.64; 95% confidence interval, 1.37–1.98). CONCLUSION: The incidence of CVD after delivery was higher in women who had preeclampsia during pregnancy.

Prenatally detected thoracic neuroblastoma

Neuroblastoma is the most common pediatric extracranial solid tumor derived from primitive neural crest cells of the sympathetic nervous system. Although one-fifths of all neuroblastomas occurs within the thorax, thoracic neuroblastomas detected in fetus have been rarely reported. We report a case of fetal thoracic neuroblastoma with massive pleural effusion detected with prenatal ultrasonography. A 34-year-old Korean second-gravida was referred to our hospital at 30 weeks of gestation for evaluation, after the right lung mass found in the fetus. Approximately 3 cm, well-defined, hyperechoic mass was found in the right thorax with right pleural effusion, with the initial suspicion of teratoma. However, as mass continued to grow with deteriorating pleural effusion and fetal hydrops, the mass was considered malignant after 3 weeks. After a cesarean delivery, an approximately 4 cm mass with peripheral calcification and hemothorax was found on neonatal ultrasonography. Neuroblastoma was diagnosed on excision biopsy.

The Amelioration Effect of the Ethanolic Extract of Cnidium officinale in Mice with Imiquimod-induced Psoriasis-like Skin Lesion

Psoriasis is an auto-immune skin disease, which is characterized by the excessive generation of plaques on the skin with typically a long-lasting red, itchy and scaly symptoms. Imiquimod, which has been used for the treatment of external genital warts, actinic keratosis, and superficial basal cell carcinoma, induced of psoriasis-like skin disorders with skin erythema and thickness in mice. In the present study, we tried to find the bioactive herbal extract against imiquimod-induced psoriasis-like skin disorder in mice. During the searching of the herbal extract with anti-psoriatic effect, the ethanolic extract of Cnidium officinale ameliorated imiquimodinduced psoriasis-like skin disorder in mice. The morphological evaluation, H&E staining and Psoriasis Area and Severity Index (PASI) score showed that ear and back thickness, and erythema induced by imiquimod were significantly reversed after the treatment of the cream of the ethanolic extract of C. officinale. The overexpressed myeloperoxidase (MPO) and keratin 6A levels were decreased by the treatment of C. officinale cream. Also, IFN-γ, c-fos and IκB-α mRNA levels, which are related to the progression of psoriasis, were reduced by C. officinale cream. Thus, the ethanolic extract of C. officinale ameliorated psoriasis-like skin disorder induced by imiquimod and might be the therapeutic agent for psoriasis.

The Level of Serum and Urinary Nephrin in Normal Pregnancy and Pregnancy with Subsequent Preeclampsia

PURPOSE: The aim of this study was to evaluate serum and urinary nephrin levels of normal pregnancy to establish a standard reference value and to compare them with patients who subsequently developed preeclampsia (PE). MATERIALS AND METHODS: In this prospective study, 117 healthy singleton pregnancies were enrolled between 6 to 20 weeks of gestation at 2 participating medical centers during October 2010 to March 2012. Urine and serum samples were collected at the time of enrollment, each trimester, and at 4 to 6 weeks postpartum. Enzyme-linked immunosorbent assay for nephrin was performed and samples from patients who subsequently developed PE were compared to the normal patients. RESULTS: Of 117 patients initially enrolled, 99 patients delivered at the study centers and of those patients, 12 (12.1%) developed PE at a median gestational age of 34⁺⁴ weeks (range 29⁺⁵–36⁺⁶). In the normal patients (n=68), serum nephrin level decreased and urinary nephrin level increased during the latter of pregnancy. In 12 patients who subsequently developed PE, a significant rise in the 3rd trimester serum and urinary nephrin levels, compared to the controls, was observed (p<0.001), and this increase occurred 9 days prior to the onset of clinical disease. CONCLUSION: As the onset of PE was preceded by the rise in the serum and urinary nephrin in comparison to normal pregnancy, serum and urinary nephrin may be a useful predictive marker of PE.

Part 7. Neonatal resuscitation: 2015 Korean Guidelines for Cardiopulmonary Resuscitation

No abstract available.

A diagnosis of hypochondroplasia by next generation sequencing

Achondroplasia and hypochondroplasia are the two most common forms of short-limb dwarfism. They are autosomal dominant diseases that are characterized by a rhizomelic shortening of the limbs, large head with frontal bossing, hypoplasia of the mid-face, genu varum and trident hands. Mutations in the fibroblast growth factor receptor-3 (FGFR3) gene, which is located on chromosome 4p16.3, have been reported to cause achondroplasia and hypochondroplasia. More than 98% of achondroplasia cases are caused by the G380R mutation (c.1138G>A or c.1138G>C). In contrast, the N540K mutation (c.1620C>A) is detected in 60-65% of hypochondroplasia cases. Tests for common mutations are often unable to detect the mutation in patients with a clinical diagnosis of hypochondroplasia. In this study, we presented a case of familial hypochondroplasia with a rare mutation in FGFR3 identified by next generation sequencing.

The risk of emergency cesarean section after failure of vaginal delivery according to prepregnancy body mass index or gestational weight gain by the 2009 Institute of Medicine guidelines

OBJECTIVE: To evaluate the risk of emergency cesarean section according to the prepregnancy body mass index (BMI) and gestational weight gain per the 2009 Institute of Medicine guidelines. METHODS: A retrospective analysis of data from 2,765 women with singleton full-term births (2009 to 2012) who attempted a vaginal delivery was conducted. Pregnancies with preeclampsia, chronic hypertension, diabetes, planned cesarean section, placenta previa, or cesarean section due to fetal anomalies or intrauterine growth restriction were excluded. Odds ratios (ORs) and confidence intervals (CIs) for emergency cesarean section were calculated after adjusting for prepregnancy BMI or gestational weight gain. RESULTS: Three-hundred and fifty nine (13.0%) women underwent emergency cesarean section. The adjusted OR for overweight, obese, and extremely obese women indicated a significantly increased risk of cesarean delivery. Gestational weight gain by Institute of Medicine guidelines was not associated with an increased risk of cesarean delivery. However, inadequate and excessive weight gain in obese women was highly associated with an increased risk of emergency cesarean section, compared to these in normal BMI (OR, 5.56; 95% CI, 1.36 to 22.72; OR, 3.63; 95% CI, 1.05 to 12.54; respectively), while there was no significant difference between normal BMI and obese women with adequate weight gain. CONCLUSION: Obese women should be provided special advice before and during pregnancy for controlling weight and careful consideration should be needed at the time of vaginal delivery to avoid emergency cesarean section.

Feasibility of three-dimensional reconstruction and automated measurement of fetal long bones using 5D Long Bone

OBJECTIVE: To evaluate the feasibility of five-dimensional Long Bone (5D LB), a new technique that automatically archives, reconstructs images, and measures lengths of fetal long bones, to assess whether the direction of volume sweep influences fetal long bone measurements in three-dimensional (3D) ultrasound and 5D LB, and to compare measurements of fetal long bone lengths obtained with 5D LB and those obtained with conventional two-dimensional (2D) and manual 3D techniques. METHODS: This prospective study included 39 singleton pregnancies at 26+0 to 32+0 weeks of gestation. Multiple pregnancies, fetuses with multiple congenital anomalies, and mothers with underlying medical diseases were excluded. Fetal long bones of the lower extremities-the femur, tibia, and fibula were measured by 2D and 3D ultrasound, and 5D LB, by an expert and non-expert examiner. First, we analyzed the 3D ultrasound and 5D LB data according to 2 different sweeping angles. We analyzed intra- and inter-observer variability and agreement between ultrasound techniques. Paired t-test, interclass correlation coefficient, and Bland-Altman plot and Passing-Bablok regression were used for statistical analysis. RESULTS: There was no statistical difference between long bone measurements analyzed according to 2 different volume-sweeping angles by 3D ultrasound and 5D LB. Intra- and inter-observer variability were not significantly different among all 3 ultrasound techniques. Comparing 2D ultrasound and 5D LB, the interclass correlation coefficient for femur, tibia, and fibula was 0.91, 0.92, and 0.89, respectively. CONCLUSION: 5D LB is reproducible and comparable with conventional 2D and 3D ultrasound techniques for fetal long bone measurement.