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Background: Complete surgical removal of pancreatic ductal adenocarcinoma (PDAC) is central to all curative treatment approaches for this aggressive disease, yet this is only possible in patients technically amenable to resection. Hence, an accurate assessment of whether patients are suitable for surgery is of paramount importance. The SCANPatient trial aims to test whether implementing a structured synoptic radiological report results in increased institutional accuracy in defining surgical resectability of non-metastatic PDAC., Methods: SCANPatient is a batched, stepped wedge, comparative effectiveness, cluster randomised clinical trial. The trial will be conducted at 33 Australian hospitals all of which hold regular multi-disciplinary team meetings (MDMs) to discuss newly diagnosed patients with PDAC. Each site is required to manage a minimum of 20 patients per year (across all stages). Hospitals will be randomised to begin synoptic reporting within a batched, stepped wedge design. Initially all hospitals will continue to use their current reporting method; within each batch, after each 6-month period, a randomly selected group of hospitals will commence using the synoptic reports, until all hospitals are using synoptic reporting. Each hospital will provide data from patients who (i) are aged 18 or older; (ii) have suspected PDAC and have an abdominal CT scan, and (iii) are presented at a participating MDM. Non-metastatic patients will be documented as one of the following categories: (1) locally advanced and surgically unresectable; (2) borderline resectable; or (3) anatomically clearly resectable (Note: Metastatic disease is treated as a separate category). Data collection will last for 36 months in each batch, and a total of 2400 patients will be included., Discussion: Better classifying patients with non-metastatic PDAC as having tumours that are either clearly resectable, borderline or locally advanced and unresectable may improve patient outcomes by optimising care and treatment planning. The borderline resectable group are a small but important cohort in whom surgery with curative intent may be considered; however, inconsistencies with definitions and an understanding of resectability status means these patients are often incorrectly classified and hence overlooked for curative options., Trial Registration: The SCANPatient trial was registered on 17th May 2023 in the Australian New Zealand Clinical Trials Registry (ANZCTR) (ACTRN12623000508673)., (© 2024. The Author(s).)

Background: Although pregnancy-associated heart failure with preserved ejection fraction (HFpEF) is increasing and contributing to maternal morbidity, little is known about its impact on pregnancy. We examined the risk factors for and adverse pregnancy outcomes of HFpEF in pregnant women., Methods: We conducted a cross-sectional analysis of pregnancy-related hospitalizations from 2009 to 2020 using the perinatal database of seven multicenters. Cases of HFpEF were identified using the International Classification of Diseases and echocardiography findings. The patients were categorized into the HFpEF and control groups. Risk factors were evaluated using multivariate logistic regression analysis to generate odds ratios (OR) and 95% confidence intervals (CI). Furthermore, adjusted associations between HFpEF and adverse pregnancy outcomes were determined. Risk scores for the stratification of women at a high risk of HFpEF were calculated using a statistical scoring model., Results: Of the 34,392 women identified, 258 (0.76%) were included in the HFpEF group. In multivariate analysis, HFpEF was significantly associated with old maternal age (OR, 1.04; 95% CI 1.02-1.07), multiple pregnancy (OR, 2.22; 95% CI 1.53-3.23), rheumatic disease (OR, 2.56; 95% CI 1.54-4.26), pregnancy induce hypertension (OR 6.02; 95% CI 3.61-10.05), preeclampsia (OR 24.66; 95% CI 18.61-32.66), eclampsia or superimposed preeclampsia (OR 32.74; 95% CI 21.60-49.64) and transfusion in previous pregnancy (OR 3.89; 95% CI 1.89-8.01). A scoring model to predict HFpEF with those factors achieved an area under the curve of 0.78 at cutoff value of 3. Women with HFpEF also had increased odds ratios of intensive care unit admission during the perinatal period (odds ratio, 5.98; 95% confidence interval, 4.36-8.21) and of postpartum hemorrhage (odds ratio, 5.98; 95% confidence interval, 2.02-3.64)., Conclusions: Pregnancy-associated HFpEF is associated with adverse pregnancy outcomes. A scoring model may contribute to screening HFpEF using echocardiography and preparing adverse pregnancy outcomes., (© 2024. The Author(s).)

Background: Ubiquitin-related rare diseases are generally characterized by developmental delays and mental retardation, but the exact incidence or prevalence is not yet fully understood. The clinical application of next-generation sequencing for pediatric seizures and developmental delay of unknown causes has become common in studies aimed at identification of a causal gene in patients with ubiquitin-related rare diseases that cannot be diagnosed using conventional fluorescence in situ hybridization or chromosome microarray tests. Our study aimed to investigate the effects of ubiquitin-proteasome system on ultra-rare neurodevelopmental diseases, through functional identification of candidate genes and variants., Methods: In our present work, we carried out genome analysis of a patient with clinical phenotypes of developmental delay and intractable convulsion, to identify causal mutations. Further characterization of the candidate gene was performed using zebrafish, through gene knockdown approaches. Transcriptomic analysis using whole embryos of zebrafish knockdown morphants and additional functional studies identified downstream pathways of the candidate gene affecting neurogenesis., Results: Through trio-based whole-genome sequencing analysis, we identified a de novo missense variant of the ubiquitin system-related gene UBE2H (c.449C>T; p.Thr150Met) in the proband. Using zebrafish, we found that Ube2h is required for normal brain development. Differential gene expression analysis revealed activation of the ATM-p53 signaling pathway in the absence of Ube2h. Moreover, depletion of ube2h led to induction of apoptosis, specifically in the differentiated neural cells. Finally, we found that a missense mutation in zebrafish, ube2h (c.449C>T; p.Thr150Met), which mimics a variant identified in a patient with neurodevelopmental defects, causes aberrant Ube2h function in zebrafish embryos., Conclusion: A de novo heterozygous variant in the UBE2H c.449C>T (p.Thr150Met) has been identified in a pediatric patient with global developmental delay and UBE2H is essential for normal neurogenesis in the brain., (© 2023. The Author(s).)

Background: Chorioamnionitis is a common cause of preterm birth and leads to serious complications in newborns. The objective of this study was to investigate the role of the Hippo signaling pathway in lung branching morphogenesis under a lipopolysaccharide (LPS)-induced inflammation model., Materials and Methods: IMR-90 cells and ex vivo fetal lungs were treated with 0, 10, 30, or 50 μg/ml LPS for 24 and 72 h. Supernatant levels of lactate dehydrogenase (LDH), interleukin (IL)-6, IL-8, Chemokine (C-X-C motif) ligand 1(CXCL1), branching and the surface area ratio, Yes-associated protein (YAP), transcription coactivator with PDZ-binding motif (TAZ), fibroblast growth factor 10 (FGF10), fibroblast growth factor receptor II (FGFR2), SRY-box transcription factor 2 (SOX2), SOX9, and sirtuin 1 (SIRT1) levels were examined. Differentially expressed genes in fetal lungs after LPS treatment were identified by RNA-sequencing., Results: LPS at 50 μg/ml increased IL-6 and IL-8 in IMR-90 cells and increased IL-6, CXCL1 and LDH in fetal lungs. The branching ratio significantly increased by LPS at 30 μg/ml compared to the control but the increased level had decreased by 50 μg/ml LPS exposure. Exposure to 50 μg/ml LPS increased phosphorylated (p)-YAP, p-YAP/YAP, and p-TAZ/TAZ in IMR-90 cells, whereas 50 μg/ml LPS decreased FGF10 and SOX2. Consistently, p-YAP/YAP and p-TAZ/TAZ were increased in fibronectin + cells of fetal lungs. Moreover, results of RNA-sequencing in fetal lungs showed that SMAD, FGF, IκB phosphorylation, tissue remodeling and homeostasis was involved in branching morphogenesis following exposure to 50 μg/ml LPS. The p-SIRT1/SIRT1 ratio increased in IMR-90 cells by LPS treatment., Conclusions: This study showed that regulation of the Hippo pathway in fibroblasts of fetal lungs was involved in branching morphogenesis under an inflammatory disease such as chorioamnionitis., (© 2023. The Author(s).)

Background: The purpose of this study was to investigate the effects of polycyclic aromatic hydrocarbons (PAHs) other than bisphenol A (BPA) and BPA substitutes on placental cells., Methods: HTR-8/SVneo cells were treated with anthracene, benzo[k]fluoranthene, benzo[a]pyrene, and 4,4-(9-fluorenylidene)diphenol, which is used as a substitute for BPA-free products. After confirming the dose response for each reagent using the prepared cells, the cells were incubated for 24, 48, and 72 h. Cell viability was confirmed using the XTT assay. Each experiment was performed with the minimum number of samples (n = 3) required for statistical analysis. The results were analyzed using t-tests; p < 0.05 was considered statistically significant., Results: After treatment with anthracene, benzo[k]fluoranthene, benzo[a]pyrene, and 4,4-(9-fluorenylidene)diphenol, the absorbance measured using the XTT assay decreased significantly with increasing concentration. The absorbance decreased significantly over time following treatment with each endocrine disruptor at the concentration confirmed by the dose-response analysis., Conclusions: This study showed that anthracene, benzo[k]fluoranthene, benzo[a]pyrene, and 4,4-(9-fluorenylidene)diphenol-a BPA substitute-affect cell viability and necrosis in the placental cell line. The study indicates the serious effects of PAHs that negatively affect pregnancy but were previously unknown. Further, this study would serve as a reference for the identification of harmful PAHs during pregnancy prognosis in women who are more susceptible to PAH exposure., (© 2022. The Author(s).)

Background: We aimed to evaluate the feasibility of the upper thigh level as a landmark to measure muscle area for sarcopenia assessment on computed tomography (CT)., Methods: In the 116 healthy subjects who performed CT scans covering from mid-abdomen to feet, the skeletal muscle area in the upper thigh level at the inferior tip of ischial tuberosity (SMA UT ), the mid-thigh level (SMA MT ), and L3 inferior endplate level (SMA L3 ) were measured by two independent readers. Pearson correlation coefficients between SMA UT , SMA MT , and SMA L3 were calculated. Inter-reader agreement between the two readers were evaluated using intraclass correlation coefficient (ICC) and Bland-Altman plots with 95% limit of agreement (LOA)., Results: In readers 1 and 2, very high positive correlations were observed between SMA UT and SMA MT (r = 0.91 and 0.92, respectively) and between SMA UT and SMA L3 (r = 0.90 and 0.91, respectively), while high positive correlation were observed between SMA MT and SMA L3 (r = 0.87 and 0.87, respectively). Based on ICC values, the inter-reader agreement was the best in the SMA UT (0.999), followed by the SMA L3 (0.990) and SMA MT (0.956). The 95% LOAs in the Bland-Altman plots indicated that the inter-reader agreement of the SMA UT (- 0.462 to 1.513) was the best, followed by the SMA L3 (- 9.949 to 7.636) and SMA MT (- 12.105 to 14.605)., Conclusion: Muscle area measurement at the upper thigh level correlates well with those with the mid-thigh and L3 inferior endpoint level and shows the highest inter-reader agreement. Thus, the upper thigh level might be an excellent landmark enabling SMA UT as a reliable and robust biomarker for muscle area measurement for sarcopenia assessment., (© 2022. The Author(s).)

Background: Although the World Health Organization and health authorities in most countries recommend that pregnant women receive inactivated influenza virus vaccines, coverage remains low. This study aimed to investigate (1) the proportion of pregnant women who received an influenza vaccination and influencing factors and (2) the proportion of obstetrics and gynecology (OBGYN) doctors who routinely recommend influenza vaccination to pregnant women and influencing factors., Methods: Two separate, anonymized questionnaires were developed for physicians and pregnant and postpartum women and were distributed to multicenters and clinics in South Korea. The proportions of women who received influenza vaccination during pregnancy and OBGYN doctors who routinely recommend the influenza vaccine to pregnant women were analyzed. Independent influencing factors for both maternal influenza vaccination and OBGYN doctors' routine recommendations to pregnant women were analyzed using log-binomial regression analysis., Results: The proportion of self-reported influenza vaccination during pregnancy among 522 women was 63.2%. Pregnancy-related independent factors influencing maternal influenza vaccination were "(ever) received information about influenza vaccination during pregnancy" (OR 8.9, 95% CI 4.17-19.01), "received vaccine information about from OBGYN doctors" (OR 11.44, 95% CI 5.46-24.00), "information obtained from other sources" (OR 4.38, 95% CI 2.01-9.55), and "second/third trimester" (OR 2.41, 95% CI 1.21-4.82).. Among 372 OBGYN doctors, 76.9% routinely recommended vaccination for pregnant women. Independent factors effecting routine recommendation were "working at a private clinic or hospital" (OR 5.33, 95% CI 2.44-11.65), "awareness of KCDC guidelines" (OR 3.11, 95% CI 1.11-8.73), and "awareness of the 2019 national free influenza vaccination program for pregnant women" (OR 4.88, 95% CI 2.34-10.17). OBGYN doctors most commonly chose 'guidelines proposed by the government or public health (108, 46%) and academic committees (59, 25%), as a factor which expect to affect the future recommendation CONCLUSION: This study showed that providing information about maternal influenza vaccination, especially by OBGYN doctors, is crucial for increasing vaccination coverage in pregnant women. Closer cooperation between the government and OBGYN academic societies to educate OBGYN doctors might enhance routine recommendations., (© 2021. The Author(s).)

Alzheimer's disease (AD) is the most common cause of age-related dementia. Increasing evidence suggests that neuroinflammation mediated by microglia and astrocytes contributes to disease progression and severity in AD and other neurodegenerative disorders. During AD progression, resident microglia undergo proinflammatory activation, resulting in an increased capacity to convert resting astrocytes to reactive astrocytes. Therefore, microglia are a major therapeutic target for AD and blocking microglia-astrocyte activation could limit neurodegeneration in AD. Here we report that NLY01, an engineered exedin-4, glucagon-like peptide-1 receptor (GLP-1R) agonist, selectively blocks β-amyloid (Aβ)-induced activation of microglia through GLP-1R activation and inhibits the formation of reactive astrocytes as well as preserves neurons in AD models. In two transgenic AD mouse models (5xFAD and 3xTg-AD), repeated subcutaneous administration of NLY01 blocked microglia-mediated reactive astrocyte conversion and preserved neuronal viability, resulting in improved spatial learning and memory. Our study indicates that the GLP-1 pathway plays a critical role in microglia-reactive astrocyte associated neuroinflammation in AD and the effects of NLY01 are primarily mediated through a direct action on Aβ-induced GLP-1R + microglia, contributing to the inhibition of astrocyte reactivity. These results show that targeting upregulated GLP-1R in microglia is a viable therapy for AD and other neurodegenerative disorders.

Background: Our objective was to evaluate risks of adverse obstetric outcomes in pregnancies with myoma(s) or in pregnancies following myomectomy., Methods: We analyzed the national health insurance database, which covers almost the entire Korean population, between 2004 and 2015. The risks of adverse pregnancy outcomes in pregnancies with myoma(s) or in pregnancies following myomectomy, compared to those in women without a diagnosed myoma, were analyzed in multivariate logistic regression analysis., Results: During the study period, 38,402 women with diagnosed myoma(s), 9890 women with a history of myomectomy, and 740,675 women without a diagnosed myoma gave birth. Women with a history of diagnosed myoma(s) and women with a history of myomectomy had significantly higher risks of cesarean section (aOR 1.13, 95% CI 1.1-1.16 and aOR 7.46, 95% CI 6.97-7.98, respectively) and placenta previa (aOR 1.41, 95% CI 1.29-1.54 and aOR 1.58, 95% CI 1.35-1.83, respectively), compared to women without a diagnosed myoma. And the risk of uterine rupture was significantly higher in women with previous myomectomy (aOR 12.78, 95% CI 6.5-25.13), compared to women without a diagnosed myoma, which was much increased (aOR 41.35, 95% CI 16.18-105.69) in nulliparous women. The incidence of uterine rupture was the highest at delivery within one year after myomectomy and decreased over time after myomectomy., Conclusions: Women with a history of myomectomy had significantly higher risks of cesarean section and placenta previa compared to women without a diagnosed myoma.

Background: The objective of this study was to investigate whether a pregnancy experience program (PREP) simulating physical changes in a mother during the last trimester of pregnancy could increase empathy, understanding, and positive attitude of medical/nursing students and their professional counterparts., Methods: This was a prospective observational study on medical/nursing students and their professional counterparts. Jefferson Scale of Physician Empathy (JSPE), physical difficulty and positive attitude score, and perceived effectiveness scores prior to PREP were compared to those after PREP., Results: A total of 189 participants completed PREP and questionnaires both prior to and after PREP. Mean JSPE score, physical difficulty score, and positive attitude scores were significantly increased following PREP (p<0.001, all). Perceived effectiveness scores about awareness, empathy, and understanding after PREP were significantly high in the professional group than in the student group (p=0.004, p=0.01, and p=0.017, respectively). Multiple stepwise linear regression analysis revealed that major in medicine (p = 0.014), health care professionals (nurse or physician) (p<0.001), and marriage experience (p < 0.001) were significant predictors of increasing empathy, difficulty feelings and effectiveness scores, respectively., Conclusion: PREP is an effective simulation program that can improve empathy, positive attitude, and awareness in medical/nursing students as well as their professional counterparts.

Background: Among the non-invasive screening methods for the identification of fetal aneuploidy, NIPT (non-invasive prenatal testing) shows the highest sensitivity and specificity in high-risk pregnancies. Due to the low false positive rate of NIPT, it is assumed that the implementation of NIPT as a primary screening method may reduce the number of invasive fetal tests and result in a similar or lowered cost in the overall detection of Down syndrome. However, most previous studies are based on theoretical economic analysis. This study aims to determine the cost effectiveness of various prenatal test strategies, including NIPT, in real clinical settings in both low risk and high risk pregnancies., Methods/design: In this prospective observational study, women (< 24 weeks) with singleton or twin pregnancies will be enrolled in 12 different healthcare institutions. The participants will be grouped based on the risks of fetal chromosomal abnormalities and will be counseled on the various screening or diagnostic methods, including NIPT, according to the aneuploidy risk. The final decision on screening or diagnostic methods will be made by patients after counseling. Questionnaires regarding factors affecting the decision on prenatal test will be answered by the participants and physicians. The economic analysis on final total costs will be compared according to the various prenatal test strategies., Discussion: The results of present study are expected to have a significant impact on national policies in determining Korean prenatal screening test strategies and to help in developing novel and effective prenatal screening tests in the future.

Alpha-synuclein (α-SYN) is one of the key contributors in Parkinson's disease (PD) pathogenesis. Despite the fact that increased α-SYN levels are considered one of the key contributors in developing PD, the molecular mechanisms underlying the regulation of α-SYN still needs to be elucidated. Since the 3' untranslated regions (3'UTRs) of messenger RNAs (mRNAs) have important roles in translation, localization, and stability of mRNAs through RNA binding proteins (RBPs) and microRNAs (miRNAs), it is important to identify the exact length of 3'UTRs of transcripts in order to understand the precise regulation of gene expression. Currently annotated human α-SYN mRNA has a relatively long 3'UTR (2529 nucleotides [nt]) with several isoforms. RNA-sequencing and epigenomics data have suggested, however, the possible existence of even longer transcripts which extend beyond the annotated α-SYN 3'UTR sequence. Here, we have discovered the novel extended form of α-SYN 3'UTR (3775 nt) in the substantia nigra of human postmortem brain samples, induced pluripotent stem cell (iPSC)-derived dopaminergic neurons, and other human neuronal cell lines. Interestingly, the longer variant reduced α-SYN translation. The extended α-SYN 3'UTR was significantly lower in iPSC-derived dopaminergic neurons from sporadic PD patients than controls. On the other hand, α-SYN protein levels were much higher in PD cases, showing the strong negative correlation with the extended 3'UTR. These suggest that dysregulation of the extended α-SYN 3'UTR might contribute to the pathogenesis of PD.

Heterozygous mutations in glucocerebrosidase 1 (GBA1) are a major genetic risk factor for Parkinson's disease and Dementia with Lewy bodies. Mutations in GBA1 leads to GBA1 enzyme deficiency, and GBA1-associated parkinsonism has an earlier age of onset and more progressive parkinsonism. To investigate a potential influence of GBA1 deficiency caused by mutations in GBA1 on the disease progression of PD, GBA1 mice carrying D409H knock-in mutation were crossbred with the human A53T (hA53T) α-synuclein transgenic mice. Here, we show that GBA1 enzyme activity plays a significant role in the hA53T α-synuclein induced α-synucleinopathy. The expression of D409H GBA1 markedly shortens the lifespan of hA53T α-synuclein transgenic mice. Moreover, D409H GBA1 expression exacerbates the formation of insoluble aggregates of α-synuclein, glial activation, neuronal degeneration, and motor abnormalities in the hA53T α-synuclein transgenic mice. Interestingly, the expression of D409H GBA1 results in the loss of dopaminergic neurons in the substantia nigra pars compacta of hA53T transgenic mice. Taken together, these results indicate that GBA1 deficiency due to D409H mutation affects the disease onset and course in hA53T α-synuclein transgenic mice. Therefore, strategies aimed to maintain GBA1 enzyme activity could be employed to develop an effective novel therapy for GBA1 linked-PD and related α-synucleinopathies.

Background: Mutations in glucocerebrosidase (GBA) cause Gaucher disease (GD) and increase the risk of developing Parkinson's disease (PD) and Dementia with Lewy Bodies (DLB). Since both genetic and environmental factors contribute to the pathogenesis of sporadic PD, we investigated the susceptibility of nigrostriatal dopamine (DA) neurons in L444P GBA heterozygous knock-in (GBA +/L444P ) mice to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), a selective dopaminergic mitochondrial neurotoxin., Method: We used GBA +/L444P mice, α-synuclein knockout (SNCA -/- ) mice at 8 months of age, and adeno-associated virus (AAV)-human GBA overexpression to investigate the rescue effect of DA neuronal loss and susceptibility by MPTP. Mitochondrial morphology and functional assay were used to identify mitochondrial defects in GBA +/L444P mice. Motor behavioral test, immunohistochemistry, and HPLC were performed to measure dopaminergic degeneration by MPTP and investigate the relationship between GBA mutation and α-synuclein. Mitochondrial immunostaining, qPCR, and Western blot were also used to study the effects of α-synuclein knockout or GBA overexpression on MPTP-induced mitochondrial defects and susceptibility., Results: L444P GBA heterozygous mutation reduced GBA protein levels, enzymatic activity and a concomitant accumulation of α-synuclein in the midbrain of GBA +/L444P mice. Furthermore, the deficiency resulted in defects in mitochondria of cortical neurons cultured from GBA +/L444P mice. Notably, treatment with MPTP resulted in a significant loss of dopaminergic neurons and striatal dopaminergic fibers in GBA +/L444P mice compared to wild type (WT) mice. Levels of striatal DA and its metabolites were more depleted in the striatum of GBA +/L444P mice. Behavioral deficits, neuroinflammation, and mitochondrial defects were more exacerbated in GBA +/L444P mice after MPTP treatment. Importantly, MPTP induced PD-like symptoms were significantly improved by knockout of α-synuclein or augmentation of GBA via AAV5-hGBA injection in both WT and GBA +/L444P mice. Intriguingly, the degree of reduction in MPTP induced PD-like symptoms in GBA +/L444P α-synuclein (SNCA) -/- mice was nearly equal to that in SNCA -/- mice after MPTP treatment., Conclusion: Our results suggest that GBA deficiency due to L444P GBA heterozygous mutation and the accompanying accumulation of α-synuclein render DA neurons more susceptible to MPTP intoxication. Thus, GBA and α-synuclein play dual physiological roles in the survival of DA neurons in response to the mitochondrial dopaminergic neurotoxin, MPTP.

Background: The World Health Organization (WHO) international body mass index (BMI) cut-off points defining pre-pregnancy BMI categories in the Institute of Medicine (IOM) guidelines are not directly applicable to Asians. We aimed to define the optimal gestational weight gain (GWG) for the Korean population based on Asia-specific BMI categories., Methods: Data from 2702 live singleton deliveries in three tertiary centers between 2010 and 2011 were analyzed retrospectively. A multivariable logistic regression analysis was conducted to determine the lowest aggregated risk of composite perinatal outcomes based on Asia-specific BMI categories. The perinatal outcomes included gestational hypertensive disorder, emergency cesarean section, and fetal size for gestational age. In each BMI category, the GWG value corresponding to the lowest aggregated risk was defined as the optimal GWG., Results: Among the study population, 440 (16.3%) were underweight (BMI < 18.5), 1459 (54.0%) were normal weight (18.5 ≤ BMI < 23), 392 (14.5%) were overweight (23 ≤ BMI < 25) and 411 (15.2%) were obese (BMI ≥ 25). The optimal GWG by Asia-specific BMI category was 20.8 kg (range, 16.7 to 24.7) for underweight, 16.6 kg (11.5 to 21.5) for normal weight, 13.1 kg (8.0 to 17.7) for overweight, and 14.4 kg (7.5 to 21.9) for obese., Conclusion: Considerably higher and wider optimal GWG ranges than recommended by IOM are found in our study in order to avoid adverse perinatal outcomes. Revised IOM recommendations for GWG could be considered for Korean women according to Asian BMI categories. Further prospective studies are needed in order to determine the optimal GWG for the Korean population.

Background: Korea has experienced diverse kind of disasters these days. Among them the 2015 middle eastern respiratory syndrome (MERS) outbreak imposed great psychological stress on almost all Korean citizens. Following the MERS outbreak, government is reviewing overall infectious disease management system and prioritizing the establishment of mental health service systems for infectious disease. This study makes suggestions for implementing disaster-related mental health service systems by analyzing the example of Gyeonggi Province, which proactively intervened with residents' psychological problems caused by the large-scale outbreak of an infectious disease., Case Description: Mental health service system for MERS victims had the following two parts: a mental health service for people who had been placed in quarantine and a service provided to families of patients who had died or recovered patients. The government of Gyeonggi province, public health centers, regional and local Community Mental Health Centers and the National Center for Crisis Mental Health Management participated in this service system. Among 1221 Gyeonggi people placed in quarantine and who experienced psychological and emotional difficulties, 350 required continuing services; 124 of this group received continuing services. That is, 35 % of people who required psychological intervention received contact from service providers and received the required services., Conclusions: This study reflects a proactive monitoring system for thousands of people placed under quarantine for the first time in Korea. It is significant that the service utilization rate by a proactive manner, that is the professionals administering it actively approached and contacted people with problems rather than passively providing information was much higher than other general mental health situation in Korea. The core value of public mental health services is adequate public accessibility; it is therefore essential for governments to strengthen their professional competence and establish effective systems. These criteria should also be applied to psychological problems caused by disastrous infectious disease outbreaks.

Background: Invasive lobular carcinoma (ILC) is the second most common histologic type of breast cancer, but the prognosis of ILC is still controversial. Enhancer of Zeste homolog 2 (EZH2), the catalytic subunit of the Polycomb repressive complex 2 (PRC2), is frequently overexpressed in various cancers. This study evaluated the relationship between clinicopathologic characteristics and EZH2 expression., Methods: We retrospectively reviewed the medical records of 54 patients with ILC and selected 49 cases of ILC. Immunohistochemistry for EZH2 was undertaken., Results: We defined ILC as discohesive cells with a linear or nonlinear growth pattern. No statistically significant difference was found for most variables, including multifocality, menstrual status, body mass index, tumor stage (pT), lymph node stage (pN), estrogen receptor, and progesterone receptor. In contrast, nuclear grade was statistically significant and EZH2 expression was associated with high nuclear grade. In total, 80% of nuclear grade 3 cases had an EZH2 score of 4, and 86% of nuclear grade 1 cases had EZH2 scores of 1 and 2. Our cases had a score of 3 for tubule formation and a score of 1 for mitosis, and so the histologic grading consisted of grades 1 (7 cases) and 2 (42 cases) depending on the nuclear grade., Conclusion: Although EZH2 could not predict survival in our study, EZH2 expression was associated with a high nuclear grade. Most ILCs have histologic grade 2 with nuclear grade 2 or 3. Therefore, our opinion is that if ILC is diagnosed by separating the classic type and variants and considering both EZH2 expression and nuclear grade, EZH2 overexpression could help and the Nottingham grading system would be more accurate prognostic factor.

Background: During the first trimester of pregnancy, trophoblastic E-cadherin expression is down-regulated, thereby allowing extravillous trophoblasts (EVTs) to acquire the potential for migration and invasiveness. The aim of the present study was to investigate the role of OSM on the migration and proliferation of EVT cell line HTR8/SVneo with regard to its effects on the expression of E-cadherin and STAT3 activation., Methods: We investigated the effects of OSM on RNA and protein expression of E-cadherin by real time RT-PCR analyses, western blotting, and indirect immunofluorescence staining in HTR8/SVneo cells, as well as the effects on cell migration and proliferation. The selective signal transducer and activator of transcription (STAT)3 inhibitor, stattic, and STAT3 siRNA were used to investigate STAT3 activation by OSM., Results: OSM significantly reduced RNA and protein expression of E-cadherin. Indirect immunofluorescence staining of HTR8/SVneo cells also revealed the down-regulation of E-cadherin, compared with the controls. OSM-stimulated cell migration was attenuated by anti-gp130 antibodies. OSM-induced STAT3 phosphorylation, and the down-regulation of E-cadherin by OSM treatment was restored by stattic and STAT3 siRNA. In addition, OSM-stimulated migration and proliferation were significantly suppressed by STAT3 inhibition., Conclusions: This study suggests that OSM stimulates the migration and proliferation of EVTs during the first trimester of pregnancy through the down-regulation of E-cadherin. In addition, this study suggests that the effects of OSM on migration and proliferation are related to STAT3 activation, which is important in trophoblast invasiveness.