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Objective We present a case of choriocarcinoma in a viable pregnancy with the rare presentation of intractable lower back pain. Case report The patient is a 34-year-old multiparous woman with her second pregnancy, and a history of scoliosis with spinal fixation. Her first pregnancy was uneventful, with a term vaginal delivery. She was hospitalized four times due to intractable back pain from 25 to 31 weeks, and terminated at 31 weeks. The placenta was unremarkable on gross examination. Postpartum, the patient developed obstructive ileus, requiring a rectosigmoid resection. She was diagnosed with metastatic choriocarcinoma to the liver, para-aortic lymph nodes, and mesentery. A week later, she developed micro-thrombosis of all limbs, massive ascites, pleural effusion. Patient refused chemotherapy and died on post-operative Day 15. Conclusion Presentation of choriocarcinoma in pregnancy varies widely. Clinicians should consider the differential diagnosis of choriocarcinoma when faced with abnormal unexplained symptoms during pregnancy.

Aims/Introduction Women with excessive gestational weight gain (GWG) are at a higher risk for complications during pregnancy, such as preeclampsia. However, the association between excessive GWG and gestational diabetes mellitus (GDM) remains unclear. Materials and Methods We retrospectively reviewed 8,352 women from our obstetric database with singleton pregnancies who gave birth after 28 completed weeks of gestation between January 1, 2012, and December 31, 2016, excluding pregnancies complicated by fetal anomalies, fetal death, and overt diabetes. Diagnosis of GDM was based on the criteria recommended by the International Association of Diabetes and Pregnancy Study Groups. We used two classification methods to define excessive GWG: a weight gain above the 90th percentile of the population, or exceeding the upper range recommended by the Institute of Medicine, stratified by pre‐pregnancy body mass index. Statistical analysis was performed using multiple logistic regression to determine the association between excessive GWG and the risk of GDM. Results Overall, 1,129 women (13.5%) were diagnosed with GDM. There was no difference in GWG between women with and without GDM in the first trimester and before GDM screening. Women with GDM had significantly less GWG in the second trimester, after GDM screening, and throughout the whole gestation than women without GDM. No correlation was found between excessive GWG in the first and second trimesters, before GDM screening, and the later development of GDM. Conclusions Our results indicate that excessive GWG prior to GDM screening is not associated with an increased risk of GDM.

Aims/Introduction The association between gestational diabetes mellitus (GDM) and adverse maternal and perinatal outcomes in twin pregnancies remains unclear. This study was undertaken to highlight risk factors for GDM in women with dichorionic (DC) twins, and to determine the association between GDM DC twins and adverse maternal and perinatal outcomes in a large homogeneous Taiwanese population. Materials and Methods A retrospective cross‐sectional study was carried out on 645 women with DC twins, excluding pregnancies complicated by one or both fetuses with demise (n = 22) or congenital anomalies (n = 9), who gave birth after 28 complete gestational weeks between 1 January 2001 and 31 December 2018. Univariable and multiple logistic regression analyses were carried out. Results Maternal age >34 years (adjusted odds ratio 2.52; 95% confidence interval 1.25–5.07) and pre‐pregnancy body mass index >24.9 kg/m2 (adjusted odds ratio 2.83, 95% confidence interval 1.47–5.46) were independent risk factors for GDM in women with DC twins. Newborns from women with GDM DC twins were more likely to be admitted to the neonatal intensive care unit (adjusted odds ratio 1.70, 95% confidence interval 1.06–2.72) than newborns from women with non‐GDM DC twins. Other pregnancy and neonatal outcomes were similar between the two groups. Conclusions Advanced maternal age and pre‐pregnancy overweight or obesity are risk factors for GDM in women with DC twins. Except for a nearly twofold increased risk of neonatal intensive care unit admission of newborns, the pregnancy and neonatal outcomes for women with GDM DC twins are similar to those for women with non‐GDM DC twins., Advanced maternal age and pre‐pregnancy overweight or obesity are risk factors for gestational diabetes mellitus in women with dichorionic twins. Except for a nearly two‐fold increased risk of neonatal intensive care unit admission of newborns, the pregnancy and neonatal outcomes for women with gestational diabetes mellitus with dichorionic twins are similar to those for women with non‐gestational diabetes mellitus with dichorionic twins.

Aims/Introduction To evaluate the rate of postpartum glycemic screening tests (PGST) in women with gestational diabetes mellitus (GDM), and to investigate risk factors for abnormal PGST results. Materials and Methods We retrospectively analyzed the obstetric data of 1,648 women with GDM who gave birth after 28 completed weeks of gestation between 1 July 2011 and 31 December 2019 at Taipei Chang Gung Memorial Hospital, Taiwan. GDM was diagnosed by the International Association of Diabetes and Pregnancy Study Groups criteria. PGST was carried out at 6–12 weeks postpartum with a 75‐g, 2‐h oral glucose tolerance test, and the results were classified into normal, prediabetes and diabetes mellitus. Multiple logistic regression was used to assess the associations between various risk factors and abnormal PGST results. Results In total, 493 (29.9%) women underwent PGST and 162 (32.9%) had abnormal results, including 135 (27.4%) with prediabetes and 27 (5.5%) with diabetes mellitus. Significant risk factors for postpartum diabetes mellitus included insulin therapy during pregnancy (adjusted odds ratio [OR] 10.79, 95% confidence interval [CI] 4.07–28.58), birthweight >4,000 g (adjusted OR 10.22, 95% CI 1.74–59.89) and preterm birth 24.9 kg/m2 (adjusted OR 1.99, 95% CI 1.24–3.21) was the major risk factor for postpartum prediabetes. Conclusions Less than one‐third of women with GDM underwent PGST, and nearly one‐third of these women had abnormal results. Future efforts should focus on reducing the barriers to PGST in women with GDM.

Objective Skeletal dysplasias, caused by genetic mutations, are a heterogenous group of heritable disorders affecting bone development during fetal life. Stickler syndrome, one of the skeletal dysplasias, is an autosomal dominant connective tissue disorder caused by abnormal collagen synthesis owing to a genetic mutation in COL2A1. Case report We present the case of a 38-year-old multipara woman whose first trimester screening showed a normal karyotype. However, the bilateral femur and humerus length symmetrically shortened after 20 weeks. Next-generation sequencing for mutations in potential genes leading to skeletal dysplasia detected a novel de novo mutation (c.1438G > A, p.Gly480Arg) in COL2A1, causing Stickler syndrome type 1. This pathogenic mutation might impair or destabilize the collagen structure, leading to collagen type II, IX, and XI dysfunction. Conclusion We identified a novel de novo mutation in COL2A1 related to the STL1 syndrome and delineated the extent of the skeletal dysplasia disease spectrum.

Objective: DiGeorge syndrome (DGS) is associated with microdeletions of chromosome 22q11. It is the second most common cause of congenital heart disease and is an important consideration whenever a conotruncal cardiac anomaly is identified. The availability of noninvasive prenatal testing (NIPT) is altering the practice of prenatal genetics and maternal-fetal medicine, resulting in a decline in invasive testing. Antenatal ultrasound and other biomarkers have their own limitation. NIPT was proposed to screen DGS with cell-free DNA in Taiwan. Here, we present our experience of prenatal diagnosis of DGS in our center. Methods: This was a retrospective study between November 1, 2019, and August 31, 2020, in Taiwan. Data were collected from 7,826 pregnant women self-referred for DGS screening with massive parallel shotgun sequencing-based NIPT. High-risk cases subsequently received amniocentesis for array comparative genomic hybridization (aCGH) to confirm the diagnosis. Characteristics of pregnancies were documented when participants received the test. Report of NIPT was completed 2 weeks after the test. Follow-up on high-risk cases was completed by telephone interview on January 30, 2021. Results: Thirteen cases showed high risk by NIPT, and 7 cases were confirmed by aCGH. The sensitivity and specificity were 100% (95% confidence interval [CI] 64.57–100.00%) and 99.92% (95% CI 99.83–99.96%). The prevalence of DGS was 1 in 1,118 pregnancies. The positive predictive rate was 53.85% (95% CI 29.14–76.79%). One true positive (TP) showed US anomaly, and 5 TPs selected termination. Discussion/Conclusion: NIPT demonstrated good performance in DGS screening. Detection of 22q11.2 deletion could be combined with routine screening to facilitate proper intervention.

Background: Despite reports of the beneficial effects, such as increasing hemoglobin level and iron store in the neonatal period, of delayed cord clamping, or umbilical cord milking after delivery in healthy term-born infants, the duration of delayed clamping or rounds of milking in most previous reports were determined arbitrarily and varied widely across different studies.Methods: We prospectively recruited 80 women with normal singleton pregnancies at 38–40 weeks' gestation. Participants were classified according to the mode of delivery and randomly assigned to either collecting blood from the placenta by umbilical cord drainage (CD) or cord milking (CM), with the placenta left in the uterus. The volume of blood collected, the duration of CD, and the number of rounds of CM were recorded.Results: Collected placental residual blood volume positively correlated with birth weight, placental weight, and length of the cord. When 80% of the total placental residual blood volume collected was set as the threshold, more than 80% of women who delivered vaginally reached this level within 60 s of CD or seven repetitions of CM. This amount of blood could be obtained within 120 s of CD or after seven repetitions of CM in more than 80% of women who underwent cesarean delivery.Conclusion: In most women, regardless of birth weight and placental weight, more than 80% of placental residual blood volume could be collected by CD within 60 s after vaginal delivery, 120 s after cesarean delivery, and seven repetitions of CM in both vaginal and cesarean deliveries.

Background With advanced diagnostic techniques, early identification of fetal anomaly becomes more accurate. However, certain diseases could only be diagnosed in late gestation. Feticide was suggested to avoid delivering children with abnormalities. Recently, twin pregnancies have increased gradually, and so have their complications. Selective feticide was considered to achieve good outcome of pregnancy. This study aimed to evaluate the performance of feticide in twin pregnancy with fetal anomaly. Methods This was a retrospective study enrolled from 2009 to 2018. A total of 68 pregnancies complicated with fetal anomalies received feticide were recorded. Potassium Chloride (KCl) was injected into left ventricle to induce fetal asystole. Monochorionic twin pregnancies were excluded, maternal and fetal characteristics of 16 dichorionic twins were documented to compare the effectiveness of feticide performed before and after 24th gestational week. Results All the pregnant women received feticide smoothly without any maternal complication. The reasons for choosing feticide were divided into four groups, including morphologic defect (61.8%), genetic-chromosomal abnormality (30.9%), obstetrical complication (5.9%) and maternal request (1.5%). Mean gestational age at delivery was significantly higher in dichorionic twins underwent selective feticide before and after 24th gestational week (36.7 vs 33.4, [p

Objective: To investigate the spatial and temporal changes of soluble epoxide hydrolase (sEH) in the human placenta throughout gestation and to study the effects of hypoxia-reoxygenation (HR) on the expression of sEH in villous explants in vitro. Materials and methods: Placental samples were obtained from women of different gestation and grouped as early (8–12 weeks, n = 10), mid- (16–28 weeks, n = 6), and late gestation (38–39 weeks, n = 10) according to gestational age. Immunohistochemistry, western blot, and real-time quantitative PCR were used to assess the cellular distribution and temporal changes of sEH. Villous explant cultures were used to study the effect of HR (8 h at 2% oxygen, followed by 16 h at 8% oxygen, two cycles) on the expression of sEH. Results: Using a mouse monoclonal antibody against human sEH, immunoreactivity of sEH was observed mainly localized in the cytotrophoblasts and, to a lesser extent, the syncytiotrophoblast in the villous tissues throughout gestation. Compared to villous tissues of early gestation, the levels of sEH mRNA and protein were significantly increased in villous samples of mid- and late gestation. Furthermore, villous explants subjected to HR had significantly higher levels of sEH mRNA and protein compared to villous tissues kept at 8% oxygen throughout the experiment. Conclusion: Our results indicate that sEH is likely to play an essential role in the development of human placenta and HR is a possible factor regulating the expression of sEH in the placenta. Keywords: Soluble epoxide hydrolase, Pregnancy, Placenta, Reoxygenation

Background Intracerebral hemorrhage (ICH) induces a complex sequence of apoptotic cascades that contribute to secondary neuronal damage. Tropomyosin-related kinase receptor B (TrkB) signaling plays a crucial role in promoting neuronal survival following brain damage. Methods The present study investigated the protective effects and underlying mechanisms of TrkB activation by the specific TrkB agonist, 7,8-dihydroxyflavone (7,8-DHF), in a model of collagenase-induced ICH and in neuronal cultures. Mice subjected to collagenase-induced ICH were intraperitoneally injected with either 7,8-DHF or vehicle 10 min after ICH and, subsequently, daily for 3 days. Behavioral studies, brain edema measurement, and histological analysis were conducted. Levels of TrkB signaling-related molecules and apoptosis-related proteins were analyzed by western blots. Results Treatment with 20 mg/kg 7,8-DHF significantly improved functional recovery and reduced brain damage up to 28 days post-ICH. Reduction in neuronal death, apoptosis, and brain edema were also observed in response to 7,8-DHF treatment at 3 days post-ICH. These changes were accompanied by a significant increase in the phosphorylation of TrkB and Akt (Ser473/Thr308) at 1 and 3 days, but had no effect on Erk 44/42 phosphorylation. 7,8-DHF also enhanced the phosphorylation of Ask-1 Ser967 and FOXO-1, downstream targets of Akt at 1 and 3 days. Moreover, 7,8-DHF increased brain-derived neurotrophic factor levels at 1 day. In primary cultured neurons stimulated with hemin, 7,8-DHF promoted survival and reduced apoptosis. Furthermore, delaying the administration of 7,8-DHF to 3 h post-ICH reduced brain tissue damage and neuronal death. Conclusions Our findings demonstrate that the activation of TrkB signaling by 7,8-DHF protects against ICH via the Akt, but not the Erk, pathway. These data provide new insights into the role of TrkB signaling deficit in the pathophysiology of ICH and highlight TrkB/Akt as possible therapeutic targets in this disease.

The frequent occurrence of multidrug resistance (MDR) conferred by the overexpression of ATP-binding cassette (ABC) transporters ABCB1 and ABCG2 in cancer cells remains a therapeutic obstacle for scientists and clinicians. Consequently, developing or identifying modulators of ABCB1 and ABCG2 that are suitable for clinical practice is of great importance. Therefore, we have explored the drug repositioning approach to identify candidate modulators of ABCB1 and ABCG2 from tyrosine kinase inhibitors with known pharmacological properties and anticancer activities. In this study, we discovered that avapritinib (BLU-285), a potent, selective, and orally bioavailable tyrosine kinase inhibitor against mutant forms of KIT and platelet-derived growth factor receptor alpha (PDGFRA), attenuates the transport function of both ABCB1 and ABCG2. Moreover, avapritinib restores the chemosensitivity of ABCB1- and ABCG2-overexpressing MDR cancer cells at nontoxic concentrations. These findings were further supported by results of apoptosis induction assays, ATP hydrolysis assays, and docking of avapritinib in the drug-binding pockets of ABCB1 and ABCG2. Altogether, our study highlights an additional action of avapritinib on ABC drug transporters, and a combination of avapritinib with conventional chemotherapy should be further investigated in patients with MDR tumors.

Intrauterine growth restriction (IUGR) is a leading cause of perinatal mortality and morbidity, and IUGR survivors are at increased risk of neurodevelopmental deficits. No effective interventions are currently available to improve the structure and function of the IUGR brain before birth. This study investigated the protective effects of low‐intensity pulsed ultrasound (LIPUS) on postnatal neurodevelopmental outcomes and brain injury using a rat model of IUGR induced by maternal exposure to dexamethasone (DEX). Pregnant rats were treated with DEX (200 μg/kg, s.c.) and LIPUS daily from gestational day (GD) 14 to 19. Behavioral assessments were performed on the IUGR offspring to examine neurological function. Neuropathology, levels of neurotrophic factors, and CaMKII‐Akt‐related molecules were assessed in the IUGR brain, and expression of glucose and amino acid transporters and neurotrophic factors were examined in the placenta. Maternal LIPUS treatment increased fetal weight, fetal liver weight, and placental weight following IUGR. LIPUS treatment also increased neuronal number and myelin protein expression in the IUGR brain, and attenuated neurodevelopmental deficits at postnatal day (PND) 18. However, the number of oligodendrocytes or microglia was not affected. These changes were associated with the upregulation of brain‐derived neurotrophic factor (BDNF) and placental growth factor (PlGF) protein expression, and enhancement of neuronal CaMKII and Akt activation in the IUGR brain at PND 1. Additionally, LIPUS treatment promoted glucose transporter (GLUT) 1 production and BDNF expression in the placenta, but had no effects on GLUT3 or amino acid transporter expression. Our findings suggest that antenatal LIPUS treatment may reduce IUGR‐induced brain injury via enhancing cerebral BDNF/CaMKII/Akt signaling. These data provide new evidence that LIPUS stimulation could be considered for antenatal neuroprotective therapy in IUGR., In a rat model of IUGR, growth restriction and loss of neurons and myelin in the brain are linked to behavioral deficits.LIPUS induces cerebral BDNF/CaMKII/Akt cascade and increases placental GLUT1 and BDNF in IUGR.LIPUS could be a treatment to reverse offspring growth restriction in IUGR.

The overexpression of the human ATP-binding cassette (ABC) drug transporter ABCB1 (P-glycoprotein, P-gp) or ABCG2 (breast cancer resistance protein, BCRP) in cancer cells often contributes significantly to the development of multidrug resistance (MDR) in cancer patients. Previous reports have demonstrated that some epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) could modulate the activity of ABCB1 and/or ABCG2 in human cancer cells, whereas some EGFR TKIs are transport substrates of these transporters. Almonertinib (HS-10296) is a promising, orally available third-generation EGFR TKI for the treatment of EGFR T790M mutation-positive non-small cell lung cancer (NSCLC) in patients who have progressed on or after other EGFR TKI therapies. Additional clinical trials are currently in progress to study almonertinib as monotherapy and in combination with other agents in patients with NSCLC. In the present work, we found that neither ABCB1 nor ABCG2 confers significant resistance to almonertinib. More importantly, we discovered that almonertinib was able to reverse MDR mediated by ABCB1, but not ABCG2, in multidrug-resistant cancer cells at submicromolar concentrations by inhibiting the drug transport activity of ABCB1 without affecting its expression level. These findings are further supported by in silico docking of almonertinib in the drug-binding pocket of ABCB1. In summary, our study revealed an additional activity of almonertinib to re-sensitize ABCB1-overexpressing multidrug-resistant cancer cells to conventional chemotherapeutic drugs, which may be beneficial for cancer patients and warrant further investigation.

Background: To contribute to the WHO initiative, VISION 2020: The Right to Sight, an assessment of global vision impairment in 2020 and temporal change is needed. We aimed to extensively update estimates of global vision loss burden, presenting estimates for 2020, temporal change over three decades between 1990–2020, and forecasts for 2050. Methods: We did a systematic review and meta-analysis of population-based surveys of eye disease from January, 1980, to October, 2018. Only studies with samples representative of the population and with clearly defined visual acuity testing protocols were included. We fitted hierarchical models to estimate 2020 prevalence (with 95% uncertainty intervals [UIs]) of mild vision impairment (presenting visual acuity ≥6/18 and

A novel multitope protein-peptide vaccine against Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection and disease is described in this report. The initial development and characterization experiments are presented along with proof-of-concept studies for the vaccine candidate UB-612. UB-612 consists of eight components rationally designed for induction of potently neutralizing antibodies and broad T cell responses against SARS-CoV-2: the S1-RBD-sFc fusion protein, six synthetic peptides (one universal peptide and five SARS-CoV-2-derived peptides), a proprietary CpG TLR-9 agonist at low concentration as an excipient, and aluminum phosphate adjuvant. Through immunogenicity studies in Guinea pigs and rats, we optimized the design of protein/peptide immunogens and selected an adjuvant system, yielding a vaccine that provides excellent S1-RBD binding and high neutralizing antibody responses, robust cellular responses, and a Th1-oriented response at low doses. In challenge studies, UB- 612 vaccination reduced viral load and prevented development of disease in mouse and non-human primate challenge models. With a Phase 1 trial completed, a Phase 2 trial ongoing in Taiwan, and additional trials planned to support global authorizations, UB-612 is a highly promising and differentiated vaccine candidate for prevention of SARS-CoV-2 infection and COVID-19 disease.Author SummarySARS-CoV-2 virus, the causative agent of Coronavirus Disease 2019 (COVID-19), has spread globally since its origin in 2019, causing an unprecedented public health crisis that has resulted in greater than 4.7 million deaths worldwide. Many vaccines are under development to limit disease spread and reduce the number of cases, but additional candidates that promote a robust immune response are needed. Here, we describe a multitope protein-peptide vaccine platform that is unique among COVID-19 vaccines. The advantages of our approach are induction of both high levels of neutralizing antibodies as well as a Th/CTL response in the vaccinated host, which mimics the immune response that occurs after natural infection with SARS-CoV-2. We demonstrate that our vaccine is immunogenic and effective in preventing disease in several animal models, including AAV- hACE-2 transduced mice, and both rhesus and cynomolgus macaques. Importantly, no immunopathology was observed in the lungs of immunized animals, therefore showing that antibody-dependent enhancement (ADE) does not occur. Our study provides an additional, novel vaccine candidate for advancement in clinical trials to treat and prevent SARS-CoV-2 infection and COVID-19 disease.

Increased maternal inflammatory response has been noted in women with pregnancies complicated by preterm birth and small-for-gestational age infants. However, the association between gestational exposure to air pollutants, maternal inflammatory response, and fetal growth remains unclear. In this study, we aimed to investigate the association between exposure to air pollutants during pregnancy and the concentration of inflammatory indicators in maternal and fetal circulations, as well as fetal growth. We recruited 108 healthy pregnant women living in northern (n = 55) and southern (n = 53) areas of Taiwan and prospectively collected information of exposure to outdoor air pollutants throughout gestation. Maternal blood from each trimester and umbilical cord blood after delivery were collected and analyzed for inflammatory indicators including high sensitivity C-reactive protein (hs-CRP), interleukin-1β (IL-1β), and tumor necrosis factor (TNF)-α. Our results showed that exposure to particulate matter less than or equal to 10 μm (PM10) and ozone (O3) during the first trimester had a direct effect on reduction of birth weight, but the direct effect of PM10 mediated by hs-CRP and the direct effect of O3 mediated by TNF-α on fetal birth weight were not significant. Exposure to PM10 and PM2.5 during the second and third trimesters also directly affected birth weight. Furthermore, exposure to sulfur dioxide (SO2) caused changes in the concentrations of TNF-α in maternal blood during the second trimester, which subsequently resulted in reduced fetal weight. Together, these results indicate that exposure to air pollutants may cause both direct and indirect effects on the reduction of fetal weight.

The overexpression of ABCB1 in cancer cells is a major factor contributing to the development of multidrug resistance (MDR) and treatment failure in cancer patients. Therefore, re-sensitization of MDR cancer cells to anticancer drugs remains an important aspect in chemotherapy. The progress in developing clinically applicable synthetic inhibitors of ABCB1 has been slow, mostly due to complications associated with intrinsic toxicities and unforeseen drug-drug interactions. Here, we explored the drug-repositioning approach for cancer therapy by targeting ABCB1-mediated MDR in human cancer cells. We found that DPI-201106, a positive inotropic agent, selectively inhibits the drug efflux function of ABCB1, and in doing so, re-sensitizes ABCB1-overexpressing MDR cancer cells to conventional anticancer drugs. Furthermore, the ATPase activity of ABCB1 and docking analysis of DPI-201106 in the drug-binding pocket of ABCB1 were determined to confirm the interaction between DPI-201106 and ABCB1 protein. In summary, we revealed an additional action and a potential clinical application of DPI-201106 to reverse ABCB1-mediated MDR in human cancer cells, which may be beneficial for cancer patients who have developed multidrug resistance and no longer respond to conventional chemotherapy, and should be further investigated.

One of the major challenges in cancer chemotherapy is the development of multidrug resistance phenomenon attributed to the overexpression of ATP-binding cassette (ABC) transporter ABCB1 or ABCG2 in cancer cells. Therefore, re-sensitizing MDR cancer cells to chemotherapy by directly inhibiting the activity of ABC transporters has clinical relevance. Unfortunately, previous attempts of developing clinically applicable synthetic inhibitors have failed, mostly due to problems associated with toxicity and unforeseen drug-drug interactions. An alternative approach is by repositioning drugs with known pharmacological properties as modulators of ABCB1 and ABCG2. In this study, we discovered that the transport function of ABCB1 and ABCG2 is strongly inhibited by SIS3, a specific inhibitor of Smad3. More importantly, SIS3 enhances drug-induced apoptosis and resensitizes ABCB1- and ABCG2-overexpressing cancer cells to chemotherapeutic drugs at non-toxic concentrations. These findings are further supported by ATPase assays and by a docking analysis of SIS3 in the drug-binding pockets of ABCB1 and ABCG2. In summary, we revealed an additional action of SIS3 that re-sensitizes MDR cancer cells and a combination therapy with this drug and other chemotherapeutic agents may be beneficial for patients with MDR tumors.

Objective: To compare the risk profiles for gestational diabetes mellitus (GDM) using a one-step and two-step screening method and diagnostic criteria. Materials and methods: A retrospective cohort study was conducted among women screened using Carpenter and Coustan's (C&C) criteria (two-step method) and the International Association of the Diabetes and Pregnancy Study Groups (IADPSG) criteria (one-step method). All deliveries after 28 weeks of gestation, except for pregnancies complicated by pre-pregnancy diabetes mellitus, were analyzed. Multiple logistic regression was used to assess the associations between GDM and various potential risk factors. Results: Risk factors for C&C-defined GDM were pre-pregnancy body mass index >24.2 kg/m2 (adjusted odds ratio [OR] 2.49, 95% confidence interval [CI] 1.92–3.23), maternal age at delivery >34 years (adjusted OR 2.46, 95% CI 1.96–3.09), history of fetal death (adjusted OR 2.56, 95% CI 1.37–4.78), and chronic hypertension (adjusted OR 3.66, 95% CI 1.50–8.91). In addition to these factors, conception assisted by reproductive technology (adjusted OR 1.64, 95% CI 1.19–2.25) and genetic amniocentesis (adjusted OR 1.19, 95% CI 1.03–1.38) were IADPSG-defined GDM risk factors. Conclusion: Risk factors for GDM differ with the diagnostic criteria used. This information is important when changing GDM screening strategies from the two-step approach to the one-step approach. Keywords: Assisted reproductive technology, Body mass index, Gestational diabetes mellitus, Risk factors

The copy number variation (CNV) of 15q11.2, an emerging and common condition observed during prenatal counseling, is encompassed by four highly conserved and non-imprinted genes—TUBGCP5, CYFIP1, NIPA1, and NIPA2—which are reportedly related to developmental delays or general behavioral problems. We retrospectively analyzed 1337 samples from genetic amniocentesis for fetal CNV using microarray-based comparative genomic hybridization analysis between January 2014 and December 2019. 15q11.2 CNV showed a prevalence of 1.5% (21/1337). Separately, 0.7% was noted for 15q11.2 BP1–BP2 microdeletion and 0.8% for 15q11.2 microduplication. Compared to the normal array group, the 15q11.2 BP1–BP2 microdeletion group had more cases of neonatal intensive care unit transfer, an Apgar score of &lt, 7 at 1 min, and neonatal death. Additionally, the group was symptomatic with developmental delays and had more infantile deaths related to congenital heart disease (CHD). Our study makes a novel contribution to the literature by exploring the differences in the adverse perinatal outcomes and early life conditions between the 15q11.2 CNV and normal array groups. Parent-origin gender-based differences may help in the prognosis of the fetal phenotype, development levels should be followed up in the long term and echocardiography should be offered prenatally and postnatally for the prevention of a delayed diagnosis of CHD.

Human ATP-binding cassette (ABC) subfamily G member 2 (ABCG2) mediates the transport of a wide variety of conventional cytotoxic anticancer drugs and molecular targeted agents. Consequently, the overexpression of ABCG2 in cancer cells is linked to the development of the multidrug resistance (MDR) phenotype. TP-3654 is an experimental second-generation inhibitor of PIM kinase that is currently under investigation in clinical trials to treat advanced solid tumors and myelofibrosis. In this study, we discovered that by attenuating the drug transport function of ABCG2, TP-3654 resensitizes ABCG2-overexpressing multidrug-resistant cancer cells to cytotoxic ABCG2 substrate drugs topotecan, SN-38 and mitoxantrone. Moreover, our results indicate that ABCG2 does not mediate resistance to TP-3654 and may not play a major role in the induction of resistance to TP-3654 in cancer patients. Taken together, our findings reveal that TP-3654 is a selective, potent modulator of ABCG2 drug efflux function that may offer an additional combination therapy option for the treatment of multidrug-resistant cancers.

// Tai-Ho Hung 1 , Song-Kun Shyue 2 , Chun-Hu Wu 3 , Chien-Cheng Chen 4 , Chao-Chang Lin 4 , Che-Feng Chang 5 and Szu-Fu Chen 4, 6 1 Department of Obstetrics and Gynecology, Chang Gung Memorial Hospital at Taipei and College of Medicine, Chang Gung University, Taoyuan, Taiwan, Republic of China 2 Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan, Republic of China 3 Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, Taiwan, Republic of China 4 Department of Physical Medicine and Rehabilitation, Cheng Hsin General Hospital, Taipei, Taiwan, Republic of China 5 Department of Neurology, Yale University School of Medicine, New Haven, Connecticut, USA 6 Departments of Physiology and Biophysics, National Defense Medical Center, Taipei, Taiwan, Republic of China Correspondence to: Szu-Fu Chen, email: szufuchen@yahoo.com.tw Keywords: soluble epoxide hydrolase, traumatic brain injury, microglia, inflammation, AUDA Received: February 15, 2017 Accepted: August 17, 2017 Published: September 21, 2017 ABSTRACT Traumatic brain injury (TBI) induces a series of inflammatory processes that contribute to neuronal damage. The present study investigated the involvement of soluble epoxide hydrolase (sEH) in neuroinflammation and brain damage in mouse TBI and in microglial cultures. The effects of genetic deletion of sEH and treatment with an sEH inhibitor, 12-(3-adamantan-1-yl-ureido)-dodecanoic acid (AUDA), on brain damage and inflammatory responses were evaluated in mice subjected to controlled cortical impact. The anti-inflammatory mechanism of sEH inhibition/deletion was investigated in vitro . TBI-induced an increase in sEH protein level in the injured cortex from 1 h to 4 days and sEH was expressed in microglia. Genetic deletion of sEH significantly attenuated functional deficits and brain damage up to 28 days post-TBI. Deletion of sEH also reduced neuronal death, apoptosis, brain edema, and BBB permeability at 1 and 4 day(s). These changes were associated with markedly reduced microglial/macrophage activation, neutrophil infiltration, matrix metalloproteinase-9 activity, inflammatory mediator expression at 1 and 4 day(s), and epoxyeicosatrienoic acid (EET) degradation at 1 and 4 day(s). Administration of AUDA attenuated brain edema, apoptosis, inflammatory mediator upregulation and EET degradation at 4 days. In primary microglial cultures, AUDA attenuated both LPS- or IFN-γ-stimulated nitric oxide (NO) production and reduced LPS- or IFN-γ-induced p38 MAPK and NF-κB signaling. Deletion of sEH also reduced IFN-γ-induced NO production. Moreover, AUDA attenuated N2A neuronal death induced by BV2 microglial-conditioned media. Our results suggest that inhibition of sEH may be a potential therapy for TBI by modulating the cytotoxic functions of microglia.

Introduction A novel amyloid β (Aβ) synthetic peptide vaccine (UB-311) has been evaluated in a first-in-human trial with patients of mild-to-moderate Alzheimer's disease. We describe translational research covering vaccine design, preclinical characterization, and phase-I clinical trial with supportive outcome that advances UB-311 into an ongoing phase-II trial. Methods UB-311 is constructed with two synthetic Aβ1–14–targeting peptides (B-cell epitope), each linked to different helper T-cell peptide epitopes (UBITh®) and formulated in a Th2-biased delivery system. The hAPP751 transgenic mouse model was used to perform the proof-of-concept study. Baboons and macaques were used for preclinical safety, tolerability, and immunogenicity evaluation. Patients with mild-to-moderate Alzheimer's disease (AD) were immunized by intramuscular route with 3 doses of UB-311 at weeks 0, 4, and 12, and monitored until week 48. Safety and immunogenicity were assessed per protocol, and preliminary efficacy was analyzed by Alzheimer's Disease Assessment Scale–Cognitive Subscale (ADAS-Cog), Mini–Mental State Examination (MMSE), and Alzheimer's Disease Cooperative Study–Clinician's Global Impression of Change (ADCS-CGIC). Results UB-311 covers a diverse genetic background and facilitates strong immune response with high responder rate. UB-311 reduced the levels of Aβ1–42 oligomers, protofibrils, and plaque load in hAPP751 transgenic mice. Safe and well-tolerated UB-311 generated considerable site-specific (Aβ1–10) antibodies across all animal species examined. In AD patients, UB-311 induced a 100% responder rate; injection site swelling and agitation were the most common adverse events (4/19 each). A slower rate of increase in ADAS-Cog from baseline to week 48 was observed in the subgroup of mild AD patients (MMSE ≥ 20) compared with the moderate AD subgroup, suggesting that UB-311 may have a potential of cognition improvement in patients with early stage of Alzheimer's dementia. Discussion The UBITh® platform can generate a high-precision molecular vaccine with high responder rate, strong on-target immunogenicity, and a potential of cognition improvement, which support UB-311 for active immunotherapy in early-to-mild AD patients currently enrolled in a phase-II trial (NCT02551809).

A proposed cascade structure of triple G m -boosting cells is proposed and applied to an OTA to enhance voltage gain and gain bandwidth product (GBW) by enhancing small-signal output currents. The proposed OTA is designed in UMC 130-nm CMOS technology. The simulated results with a 15nF load and 0.7 V supply show small-signal figure-of-merit of 260,1300 MHz$\cdot$pF/mW.

Introduction Dysregulation of placental apoptosis and autophagy are observed in pregnancy complications including preeclampsia and fetal growth restriction. However, studies of their changes in the placentas of women with gestational diabetes mellitus (GDM) show inconsistent results. We aimed to compare the changes in apoptosis, autophagy, and Bcl-2 family proteins in the placentas from women with normal pregnancies and those with GDM, with or without large-for-gestational age (LGA) infants and to investigate the effect of hyperglycemia on the changes in apoptosis, autophagy, and Bcl-2 family proteins in primary cytotrophoblastic cells. Methods Villous tissues were obtained from normal pregnant women and those with GDM, with or without LGA infants. Primary cytotrophoblast cells were isolated from normal term placentas and cultured under standard, hyperglycemic, or hyperosmotic conditions. Results Compared to placentas from normal pregnant women, those from GDM women with LGA infants were heavier, had lower beclin-1 and DRAM levels, less M30 and cleaved PARP immunoreactivity, and increased Ki-67 immunoreactivity. These changes were associated with increased Bcl-xL and decreased Bak levels. Increased glucose concentration led to lower ATG5, beclin-1, LC3B-II, p62, and DRAM levels, lower annexin V and M30-positive cell percentages, and less cleaved PARP changes compared with standard culture conditions. Hyperglycemia caused higher Bcl-xL levels and lower Bak and Bad levels than did standard culture conditions. Discussion There were differential changes in apoptosis and autophagy between placentas from normal pregnant women and those from GDM women with LGA infants. Bcl-2 family proteins are likely involved in the regulation of these changes.

Chorioamnionitis (CAM) is primarily a polymicrobial bacterial infection involving chorionic and amniotic membranes that is associated with increased risk of preterm delivery. Epoxyeicosatrienoic acids (EETs) are eicosanoids generated from arachidonic acid by cytochrome P450 enzymes and further metabolized mainly by soluble epoxide hydrolase (sEH) to produce dihydroxyeicosatrienoic acids (DHETs). As a consequence of this metabolism of EETs, sEH reportedly exacerbates several disease states; however, its role in CAM remains unclear. The objectives of this study were to (1) determine the localization of sEH and compare the changes it undergoes in the gestational tissues (placentas and fetal membranes) of women with normal-term pregnancies and those with pregnancies complicated by acute CAM; (2) study the effects of lipopolysaccharide (LPS) on the expression of sEH in the human gestational tissues; and (3) investigate the effect of 12-(3-adamantan-1-yl-ureido)-dodecanoic acid (AUDA), a specific sEH inhibitor, on LPS-induced changes in 14,15-DHET and cytokines such as interleukin- (IL-) 1β and IL-6 in human gestational tissues in vitro and in pregnant mice. We found that women with pregnancies complicated by acute CAM had higher levels of sEH mRNA and protein in fetal membranes and villous tissues compared to those in women with normal-term pregnancies without CAM. Furthermore, fetal membrane and villous explants treated with LPS had higher tissue levels of sEH mRNA and protein and 14,15-DHET than those present in the vehicle controls, while the administration of AUDA in the media attenuated the LPS-induced production of 14,15-DHET in tissue homogenates and IL-1β and IL-6 in the media of explant cultures. Administration of AUDA also reduced the LPS-induced changes of 14,15-DHET, IL-1β, and IL-6 in the placentas of pregnant mice. Together, these results suggest that sEH participates in the inflammatory changes in human gestational tissues in pregnancies complicated by acute CAM.

Ferroelectric photoelectrodes, other than conventional semiconductors, are alternative photo-absorbers in the process of water splitting. However, the capture of photons and efficient transfer of photo-excited carriers remain as two critical issues in ferroelectric photoelectrodes. In this work, we overcome the aforementioned issues by decorating the ferroelectric BiFeO3 (BFO) surface with Au nanocrystals, and thus improving the photoelectrochemical (PEC) performance of BFO film. We demonstrate that the internal field induced by the spontaneous polarization of BFO can (1) tune the efficiency of the photo-excited carriers' separation and charge transfer characteristics in bare BFO photoelectrodes, and (2) modulate an extra optical absorption within the visible light region, created by the surface plasmon resonance excitation of Au nanocrystals to capture more photons in the Au/BFO heterostructure. This study provides key insights for understanding the tunable features of PEC performance, composed of the heterostructure of noble metals and ferroelectric materials.

The development of multidrug resistance (MDR) in cancer patients, which is often associated with the overexpression of ABCB1 (MDR1, P-glycoprotein) in cancer cells, remains a significant problem in cancer chemotherapy. ABCB1 is one of the major adenosine triphosphate (ATP)-binding cassette (ABC) transporters that can actively efflux a range of anticancer drugs out of cancer cells, causing MDR. Given the lack of Food and Drug Administration (FDA)-approved treatment for multidrug-resistant cancers, we explored the prospect of repurposing erdafitinib, the first fibroblast growth factor receptor (FGFR) kinase inhibitor approved by the FDA, to reverse MDR mediated by ABCB1. We discovered that by reducing the function of ABCB1, erdafitinib significantly resensitized ABCB1-overexpressing multidrug-resistant cancer cells to therapeutic drugs at sub-toxic concentrations. Results of erdafitinib-stimulated ABCB1 ATPase activity and in silico docking analysis of erdafitinib binding to the substrate-binding pocket of ABCB1 further support the interaction between erdafitinib and ABCB1. Moreover, our data suggest that ABCB1 is not a major mechanism of resistance to erdafitinib in cancer cells. In conclusion, we revealed an additional action of erdafitinib as a potential treatment option for multidrug-resistant cancers, which should be evaluated in future drug combination trials.

The development of multidrug resistance (MDR) in cancer patients driven by the overexpression of ATP-binding cassette (ABC) transporter ABCB1 or ABCG2 in cancer cells presents one of the most daunting therapeutic complications for clinical scientists to resolve. Despite many novel therapeutic strategies that have been tested over the years, there is still no approved treatment for multidrug-resistant cancers to date. We have recently adopted a drug repurposing approach to identify therapeutic agents that are clinically active and at the same time, capable of reversing multidrug resistance mediated by ABCB1 and ABCG2. In the present study, we investigated the effect of sitravatinib, a novel multitargeted receptor tyrosine kinase inhibitor, on human ABCB1 and ABCG2 in multidrug-resistant cancer cell lines. We discovered that at submicromolar concentrations, sitravatinib re-sensitizes ABCB1- and ABCG2-overexpressing multidrug-resistant cancer cells to chemotherapeutic drugs. We found that sitravatinib blocks the drug efflux function of ABCB1 and ABCG2 in a concentration-dependent manner but does not significantly alter the protein expression of ABCB1 or ABCG2 in multidrug-resistant cancer cells. In conclusion, we reveal a potential drug repositioning treatment option for multidrug-resistant cancers by targeting ABCB1 and ABCG2 with sitravatinib and should be further investigated in future clinical trials.

Objective: To compare the efficacy of carbetocin and oxytocin on hemorrhage-related changes in women with cesarean deliveries (CS) for different indications. Materials and methods: A retrospective cohort study was conducted on 1568 women with CS before labor onset (elective CS, n = 1153) or during labor (intrapartum CS, n = 415) after 24 weeks’ gestation. We compared the fall in hemoglobin (Hb) and hematocrit (Hct) levels after CS, estimated blood loss, the need for additional uterotonic agents, blood transfusion, and the rate of postpartum hemorrhage between women with carbetocin and women with oxytocin treatment, stratified by indications for CS. Results: For women with elective CS, decreased Hb and Hct falls were noted with carbetocin treatment compared to oxytocin treatment in women with indications for prior CS, fetal malpresentation, and multiple gestation. The need for additional uterotonics was less in CS for prior CS, fetal malpresentation, and cephalopelvic disproportion and fewer transfusions in CS for multiple gestation in women with carbetocin compared to women with oxytocin treatment. For women with intrapartum CS, carbetocin was associated with decreased use of additional uterotonic agents and transfusion in CS for dysfunctional labor. Conclusion: Carbetocin and oxytocin had differential effects on hemorrhage-related changes in women with CS for different indications. Keywords: Carbetocin, Cesarean delivery, Oxytocin, Postpartum hemorrhage

A modified cascode current-mirror amplifier with double gain-boosting technique is presented in this paper. Signal-and transient-current boosting (STCB) technique is incorporated to further boost the gain of the amplifier, while the characteristic of a single-pole system is retained. Designed in CMOS 130-nm technology, the simulated results show that the output swing can be extended up to 73% and 77% of the positive and negative supply rails, respectively, under supply voltages of ± 0.6V. The proposed amplifier is able to attain a DC gain over 150 dB with its unity-gain frequency (UGF) and phase margin (PM) around 0.67 MHz and 86°, respectively, when it is loaded with a 100 pF output capacitor.

Background/Purpose Acoustic analysis is often used in speech evaluation but seldom for the evaluation of oral prostheses designed for reconstruction of surgical defect. This study aimed to introduce the application of acoustic analysis for patients with velopharyngeal insufficiency (VPI) due to oral surgery and rehabilitated with oral speech-aid prostheses. Methods The pre- and postprosthetic rehabilitation acoustic features of sustained vowel sounds from two patients with VPI were analyzed and compared with the acoustic analysis software Praat. Results There were significant differences in the octave spectrum of sustained vowel speech sound between the pre- and postprosthetic rehabilitation. Acoustic measurements of sustained vowels for patients before and after prosthetic treatment showed no significant differences for all parameters of fundamental frequency, jitter, shimmer, noise-to-harmonics ratio, formant frequency, F1 bandwidth, and band energy difference. The decrease in objective nasality perceptions correlated very well with the decrease in dips of the spectra for the male patient with a higher speech bulb height. Conclusion Acoustic analysis may be a potential technique for evaluating the functions of oral speech-aid prostheses, which eliminates dysfunctions due to the surgical defect and contributes to a high percentage of intelligible speech. Octave spectrum analysis may also be a valuable tool for detecting changes in nasality characteristics of the voice during prosthetic treatment of VPI.

Objective To compare the duration of second stage labor among modern Taiwanese women who achieved vaginal delivery without adverse neonatal outcomes and women who delivered during the early 1990s. Materials and methods Data were collected from women who underwent spontaneous labor and vaginally delivered cephalic singleton fetuses with normal neonatal outcomes at the Taipei Chang Gung Memorial Hospital, Taipei, Taiwan from 1991–1995 (Cohort 1, n = 10,721) and 2010–2014 (Cohort 2, n = 3734). We calculated the median duration and 95th percentiles of second stage labor. The women were stratified according to analgesia and parity. Multiple linear regression analysis was used to determine the association between the maternal/pregnancy characteristics and second stage labor duration. Results The median second stage labor duration was significantly longer for Cohort 2 than for Cohort 1. For nulliparous women, the 95th percentile second stage labor thresholds were 255 minutes and 152 minutes (Cohort 2) and 165 minutes and 107 minutes (Cohort 1) for women with and without epidural analgesia, respectively. For multiparous women, the 95th percentile second stage labor thresholds were 136 minutes and 43 minutes (Cohort 2) and 125 minutes and 39 minutes (Cohort 1) for women with and without epidural analgesia, respectively. Birth weight, maternal age at delivery, and time period (2010–2014 vs. 1991–1995) were significant factors associated with the duration of second stage labor. Conclusion Modern Taiwanese women who achieved vaginal delivery without adverse neonatal outcomes experienced longer second stage labors than women 25 years ago. The 95th percentile thresholds differed between nulliparous and multiparous women with and without epidural analgesia.

Objective To investigate perinatal outcomes according to the 2009 Institute of Medicine (IOM) gestational weight gain (GWG) guidelines. Materials and methods A retrospective cohort study was conducted among all term, singleton, live births to women who delivered at the Taipei Chang Gung Memorial Hospital, Taipei, Taiwan between 2009 and 2014. Women were categorized into three groups based on prepregnancy body mass index and GWG relative to the IOM guidelines. Multivariable logistic regression analysis was used to assess the associations between GWG outside the IOM guidelines and adverse perinatal outcomes. Women with GWG within the guidelines served as the reference group. Results Of 9301 pregnancies, 2574 (27.7%), 4189 (45.0%), and 2538 (27.3%) women had GWG below, within, and above the IOM guidelines. Women with GWG above the IOM guidelines were at risk for preeclampsia [adjusted odds ratio (OR) 3.0, 95% confidence interval (CI) 1.9–4.7], primary cesarean delivery (adjusted OR 1.4, 95% CI 1.2–1.6) due to dysfunctional labor and cephalopelvic disproportion, large-for-gestational age (adjusted OR 1.8, 95% CI 1.5–2.1), and macrosomic neonates (adjusted OR 2.2, 95% CI 1.6–3.1). Women with GWG below the IOM guidelines were more likely to be diagnosed with gestational diabetes mellitus (adjusted OR 1.5, 95% CI 1.3–1.8) and were at higher risk for placental abruption (adjusted OR 1.7, 95% CI 1.1–2.5), small-for-gestational age (adjusted OR 1.6, 95% CI 1.4–1.9), and low birth weight neonates (adjusted OR 1.9, 95% CI 1.4–2.4). Conclusion Women with GWG outside the 2009 IOM guidelines were at risk for adverse maternal and neonatal outcomes.

Heterostructure provides a powerful route in manipulating electrical transport, optical response, electrolytic water splitting and water treatment of complex oxides. As a model for noble metal/ complex oxide heterostructures, we have successfully prepared Au/BiVO 4 (BVO) heterostructures in which the Au nanoparticles (NPs) with various sizes and densities were uniformly deposited on the {001} facets of epitaxial BVO thin films. The heterostructures exhibit significantly enhanced photoactivities in both dye degradation and electrolytic water splitting. By employing X-ray photoelectron spectroscopy, the energy band alignment of Au/BVO heterojunction suggests a charge separation at their interfaces, that can manipulate the photoexcited electron–hole pairs and photocatalytic efficiency of the heterostructures. Photogenerated carrier injection, which mainly affects the photoactivity of photocatalysis, was detected across Au/BVO interfaces by ultrafast dynamics spectroscopy. This study delivers a general approach to probe and understand the photochemistry of noble metal-complex oxide heterostructures for photoconversion applications.

Background/purpose In the fabrication of casting post and core or inlay the line angle of the cavity floor can be seen even when the internal axial walls are parallel or slightly convergent. It is conceivable that more sighted distance will be required for internal axial walls evaluation compared with external axial walls evaluation. The aim of the study is to derive a practical and convenient method and data for the evaluation of the divergent angle of internal axial walls. Materials and methods Through a scientific analysis, this study derived a practical and convenient method and data for the evaluation of the divergent angle of internal axial walls. The sighted distance between occlusal line angle and the cavity floor line angle at 30-cm distance was calculated by an established formula and expressed in 6°, 12°, and 18° of internal axial walls divergent angle respectively. Results Tables 1–3 show the value of sighted distance with cavities of 6°, 12°, and 18° tapering. Based on the data, if more divergent angle is prepared; more sighted distance will be observed. Conclusion Compared with the teeth preparation of external axial wall in a single crown, the sighted distance at 30-cm distance in the internal axial wall is 1.5 × wider. More sighted distances are required to prevent undesired undercuts.

Aim To evaluate and compare the long-term outcome of sacrospinous ligament fixation (SSF) in combination with various other compartment defect native tissue repairs with hysterectomy or hysteropexy. Methods Medical records of 159 patients who underwent surgery for pelvic organ prolapse (POP) between April 2004 and August 2008 were reviewed retrospectively. Patients were assessed at baseline and at 5-year postoperative follow-up. SSF, anterior (AC) and posterior colporrhaphy (PC), both with and without hysterectomy, were performed. Primary outcome was objective cure (POP quantification system [POP-Q] ≤1) and subjective cure (negative response to questions 2 and 3 on Pelvic Organ Prolapse Distress Inventory 6 [POPDI-6]). Subanalysis was done on patients who had uterus preserved compared with those with vaginal hysterectomy. Results Postoperative data were available for 146 patients: 120 in the hysterectomy group and 26 in the hysteropexy group. Mean age, parity, postmenopausal status and mean operating time in the hysterectomy group were significantly higher than in the hysteropexy group. At median follow-up of 86 months, objective cure at overall compartments for all patients was 67.8%, and for subjective cure, this was 64.4%. There was no difference in the adjusted odds ratio for objective and subjective cure rates in both groups, but the hysterectomy group had a significantly lower mean total POPDI-6 score. Conclusion SSF plus AC and PC have a low reoperation rate despite a moderate success rate at 7-year follow-up. There was no difference in the adjusted objective, subjective success rates and sexual function between sacrospinous hysteropexy and hysterectomy. The hysterectomy group, however, had fewer bothersome prolapse symptoms.

Objective Difficulties often encountered during intubation in extremely low birth-weight (ELBW) neonates requiring resuscitation at birth because of the smaller airway and the pressure from the limited number of attempts before hemodynamic instability occurs. Case report We evaluated two pregnant women at 26 weeks of gestation with premature rupture of membranes and evidence of chorioamnionitis and applied the concept of ex utero intrapartum treatment, which involved delaying cord clamping (DCC) after establishing a secured airway with adequate ventilation during cesarean delivery. The resuscitative procedure was smooth and all three neonates had favorable outcomes at one month of age. Conclusion When cesarean delivery is indicated in ELBW infants and intubation after birth is anticipated, DCC after establishing a secured airway may help maintain neonatal cardiovascular stability and allow physicians to resolve the technical difficulties of intubation.

Objectives To investigate the risks of delivering small-for-gestational-age (SGA) and large-for-gestational-age (LGA) infants in women with early- (delivered before 34 weeks of gestation) and late-onset (delivered at or after 34 weeks of gestation) preeclampsia. Study design We conducted a retrospective cohort study of 29,494 singleton deliveries after 24 weeks’ gestation, excluding pregnancies complicated by fetal anomalies, stillbirths, and prepregnancy diabetes mellitus. Univariate and multivariate logistic analyses adjusted for potential confounding factors, including prepregnancy body mass index (BMI), gestational weight gain (GWG), and gestational diabetes mellitus (GDM), were performed. Results Among women who delivered before 34 weeks, significantly more women with preeclampsia delivered SGA infants than women without preeclampsia (50.6% vs. 7.0%; adjusted odds ratio [OR] 16.3; 95% confidence interval [CI] 8.1–32.9). Among women who delivered at or after 34 weeks, women with preeclampsia had higher rates of delivering SGA (25.5% vs. 7.0%) and LGA (13.7% vs. 9.9%) infants than women without preeclampsia. After adjustment for confounding factors, preeclampsia remained a significant risk factor for delivering SGA infants (adjusted OR 5.7; 95% CI 4.6–7.1), but the association between preeclampsia and the delivery of LGA infants was diminished (adjusted OR 0.8; 95% CI 0.6–1.1). Conclusions Our results confirm that preeclampsia is associated with SGA and that the association is stronger with early-onset disease. Although women with late-onset preeclampsia had a higher rate of delivering LGA infants, the association between late-onset preeclampsia and LGA is due to confounding factors, such as high prepregnancy BMI, excessive GWG, and GDM, related to maternal metabolic abnormalities.

Objective: To evaluate the outcomes associated with fetal ventriculomegaly. Materials and methods: Reports of women who underwent ultrasound scanning between 18 and 36 weeks of gestation during the period from January 1, 2000, to December 31, 2010, were reviewed. According to the defined severity of ventriculomegaly of affected fetuses, the women were divided into the following groups: (1) mild ventriculomegaly (Group A); (2) moderate ventriculomegaly (Group B); and (3) severe ventriculomegaly (Group C). The women were classified into the “gray zone” group if the fetal lateral ventricle measured between 7 mm and

Different brain tumors of distinct histology can co-exist in the setting of phakomatoses or as a complication of radiotherapy. In the absence of these predisposing factors, this phenomenon is uncommon. When the lesions are in close proximity they are described as collision tumors and are extremely rare. A 58-year-old woman presented with persistent headache and cognitive decline for three months. Magnetic resonance imaging revealed a tumor arising from the atrium of the left lateral ventricle with heterogeneous contrast enhancement. This intraventricular lesion was adjacent to another extensive infiltrating tumor of the basal cisterns. Operative findings revealed a vascular ventricular tumor and gross total resection was achieved. An adjacent avascular basal cistern tumor with a pearly white sheen was encountered and partial excision was performed. The histopathological diagnosis was central neurocytoma and epidermoid tumor. There is only one documented description of a central neurocytoma co-existing with a tumor of different pathology. To our knowledge, this is the first reported collision tumor case involving central neurocytoma. Since the incidence of both lesions co-existing juxtaposed is extremely low, a chronic oncogenetic inflammatory process stimulated by the epidermoid tumor to the subventricular region is suggested. Other mechanisms for tumor collision are discussed and we suggest a classification system for this rare association to reflect their pathogenesis.

Objective To investigate the perinatal outcomes of women who suffered from thrombocytopenia at delivery but did not have other diseases during pregnancy. Materials and Methods We considered all singleton deliveries after 24 weeks of gestation at Chang Gung Memorial Hospital, Taipei, Taiwan between 2001 and 2010. Women were excluded from this study if they suffered from any of the following conditions: chronic hypertension, hepatitis, acute fatty liver, liver cirrhosis, nephropathy, overt diabetes mellitus, connective tissue disease, systemic lupus erythematosus, or immune thrombocytopenia. Pregnancies complicated by gestational hypertension, preeclampsia, or fetal anomalies during gestation were also excluded. A total of 18,384 deliveries were included for analysis. Women were divided into three groups according to platelet count at admission. Results A total of 787 pregnancies (4.3%) were complicated by thrombocytopenia. Thrombocytopenic women had a significantly higher rate of cesarean delivery compared to women who did not have this condition. No other differences were observed among these three groups regarding the rates of adverse pregnancy outcomes. Conclusions The results indicate that women who suffered from incidental thrombocytopenia at delivery but did not have other diseases during pregnancy were not at increased risk for adverse pregnancy outcomes.

Objective: To investigate the associations between maternal pregestational body mass index (BMI), gestational weight gain (GWG), and adverse pregnancy outcomes among Taiwanese women. Materials and Methods: A retrospective cohort study was conducted among all singletons without fetal anomalies delivered to women at Taipei Chang Gung Memorial Hospital between 2009 and 2015. Two study cohorts were selected for analysis: all deliveries after 24 0/7 weeks of gestation (Cohort 1, n=12,064) and all live births after 37 0/7 weeks of gestation excluding maternal overt diabetes mellitus and chronic hypertension (Cohort 2, n=10,973). The associations between pregestational BMI, GWG outside the 2009 Institute of Medicine (IOM) guidelines, and adverse pregnancy outcomes were assessed using multivariable logistic regression analysis. Results: In Cohort 1, the prevalence of pregestational underweight, normal weight, overweight, and obesity was 14.0%, 74.8%, 9.0%, and 2.2%, respectively. Compared with the women with normal weight, maternal underweight was associated with increased risk for placental abruption, small-for-gestational age, and low birth weight (4000 g). In Cohort 2, GWG below the IOM guidelines were associated with higher rates of gestational diabetes mellitus, small-for-gestational age, and low birth weight, while GWG above the IOM guidelines were with higher rates of primary cesarean delivery, large-for-gestational age, and macrosomia in women with pregestational underweight or normal weight. Normal weight women were more likely to have placental abruption with GWG below the guidelines and to have preeclampsia with GWG above the guidelines. For overweight and obese women, GWG below the guidelines was associated with a higher rate of gestational diabetes mellitus, but GWG above the guidelines was associated with a higher rate of macrosomia. Conclusions: Women with abnormal pregestational BMI are at risk for adverse maternal and neonatal outcomes. Moreover, GWG has a differential effect on the rates of adverse pregnancy outcomes between women of different pregestational BMI categories.

We propose a depth and image scene flow estimation method taking the input of a binocular video. The key component is motion-depth temporal consistency preservation, making computation in long sequences reliable. We tackle a number of fundamental technical issues, including connection establishment between motion and depth, structure consistency preservation in multiple frames, and long-range temporal constraint employment for error correction. We address all of them in a unified depth and scene flow estimation framework. Our main contributions include development of motion trajectories, which robustly link frame correspondences in a voting manner, rejection of depth/motion outliers through temporal robust regression, novel edge occurrence map estimation, and introduction of anisotropic smoothing priors for proper regularization.

Although hyperbaric oxygen therapy has not been accepted as a standard therapy for traumatic brain injuries, it has been used, along with rehabilitative exercises, for traumatic brain injuries, and the standard protocol has a low risk of complications. We report a case of chronic traumatic brain injury that progressed to tension pneumocephalus after hyperbaric oxygen therapy. The patient was a 25-yr-old man who presented with left occipital bone fracture and subarachnoid and subdural hemorrhage after being hit by a car. He underwent craniectomy to remove the hematoma and cerebrospinal fluid diversion with a ventriculoperitoneal shunt for the treatment of hydrocephalus. Fifteen months after the trauma, the patient received hyperbaric oxygen therapy to promote functional recovery. Tension pneumocephalus developed after the first session of hyperbaric oxygen therapy, and immediate burr hole drainage followed by ligation of the ventriculoperitoneal shunt was performed. The patient's consciousness recovered gradually, and he was discharged home. We suggest that patients with unrepaired skull base fracture and cerebrospinal fluid diversion should be carefully evaluated before receiving hyperbaric oxygen therapy.

To investigate the association between maternal oxidative stress at mid-gestation and subsequent development of pregnancy complications. A total of 503 healthy pregnant women provided their blood and urine samples at 24 to 26 weeks of gestation and were prospectively followed through postpartum. These samples were used to assess a variety of oxidative stress markers, including plasma total antioxidant capacity, 8-isoprostane, erythrocyte glutathione peroxidase and superoxide dismutase activity, and urinary 8-hydroxydeoxyguanosine (8-OHdG). Compared with women with uncomplicated pregnancies, significantly higher plasma 8-isoprostane levels were noted in women who developed preeclampsia (P = .008) and small-for-gestational age infants (P = .002), while higher urinary 8-OHdG concentrations were noted in women who subsequently had low-birth-weight neonates (

Myeloperoxidase (MPO) is a heme protein produced and released by activated neutrophils and monocytes, and increased MPO is considered important in the pathophysiology of cardiovascular diseases (CVD). Accumulating evidence suggests that preeclampsia (PE), idiopathic intrauterine growth restriction (IUGR), and CVD share many similar metabolic disturbances, including an enhanced systemic inflammatory response and endothelial dysfunction. We hypothesized that MPO plays an important role in the development of PE and IUGR. Plasma samples were collected mid-gestation and at delivery from women with normal pregnancies (n = 40) and those who subsequently developed PE (n = 20), IUGR (n = 11) or both (PE + IUGR, n = 8). Placental samples were obtained immediately after delivery from 22 women with normal pregnancies, 19 women with PE, 14 women with IUGR, and 14 women with PE + IUGR. The MPO concentrations were measured using ELISA. Women with PE + IUGR had significantly higher plasma MPO before delivery than normal pregnant women. There was no difference in plasma levels at mid-gestation or the placental concentrations between women with normal pregnancies and those who developed PE, IUGR, or PE + IUGR. Using explants prepared from the placentas of 8 women with normal pregnancies and 8 women with PE, we found no difference in the levels of MPO in the tissue homogenates and culture media between these two groups of women. Together, these results indicate that increased maternal circulating MPO in women with PE + IUGR is likely a result of enhanced systemic inflammation caused by the established disease rather than a primary pathophysiological factor.

Objective To report the incidence, prenatal diagnostic rate, and postnatal outcomes of fetal orofacial cleft at a tertiary referral center in Taiwan. Methods The demographic data, maternal and fetal characteristics, and postnatal outcomes for fetuses with cleft lip and/or cleft palate (CL/P) born between January 1998 and December 2008 at Chang Gung Memorial Hospital, Taipei, were reviewed retrospectively, and diagnostic rates were evaluated according to cleft type. Results Among 26 499 deliveries, 84 were affected with CL/P. The mean maternal age and gestational age at detection of CL/P were 30.37 years (range 21–41 years) and 24.7 weeks (range 18–33 weeks), respectively. Thirty-one fetuses had associated structural anomalies, 5 of which involved chromosomal aberrations. CL/P was diagnosed prenatally for 74 (88%) fetuses. After consultations, 17 pregnancies (20%) were aborted. The postnatal survival rate was 95.5% (64/67 infants). The type of cleft had a significant influence on correct prenatal diagnosis (P Conclusion For fetuses diagnosed prenatally with an orofacial cleft, access to an experienced craniofacial team, well-planned delivery, and pediatric intensive care led to favorable postnatal outcomes after lethal malformations were excluded through detailed sonographic and chromosomal evaluations.

Pregnancy is associated with increased oxidative stress, and exaggeration of oxidative damage is considered important in pregnancy complications such as preeclampsia. There is, however, only scattered information regarding the longitudinal change of oxidative stress during pregnancy. We surmised that the placenta is the cause of the increased oxidative stress during pregnancy and hypothesized that the amount of placenta-derived cell-free fetal DNA in maternal plasma is correlated with maternal oxidative stress status. Blood and urine samples were collected at different stages of gestation and 6 to 8 weeks postpartum from 105 women with uncomplicated pregnancies. Additionally, 40 healthy women of reproductive age, but not pregnant, were recruited as controls. All oxidative stress markers, including urinary 8-hydroxydeoxyguanosine (8-OHdG), plasma 8-isoprostane, total antioxidant capacity (TAC), and erythrocyte glutathione peroxidase (GPX) and superoxide dismutase (SOD) activities, were increased in the third trimester, and most of them returned to nonpregnant levels postpartum. Furthermore, the DYS14 gene of the Y chromosome was quantified from plasma samples obtained at 26 to 30 weeks' gestation in 54 women who later delivered a male infant. Significant associations were noted between plasma concentrations of the DYS14 gene and the levels of urinary 8-OHdG and plasma 8-isoprostane, suggesting an association between the breakdown of syncytiotrophoblast and maternal oxidative stress during pregnancy.

Objective To investigate (1) whether there is an increasing trend in the mean maternal age at the birth of the first child and in the group of women giving birth at age 35 or older, and (2) the association between advanced maternal age and adverse perinatal outcomes in an Asian population. Study design We conducted a retrospective cohort study involving 39,763 Taiwanese women who delivered after 24 weeks of gestation between July 1990 and December 2003. Multivariable logistic regression was used to adjust for potential confounding variables. Results During the study period, the mean maternal age at the birth of the first child increased from 28.0 to 29.7 years, and the proportion of women giving birth at age 35 or older increased from 11.4% to 19.1%. Compared to women aged 20–34 years, women giving birth at age 35 or older carried a nearly 1.5-fold increased risk for pregnancy complications and a 1.6–2.6-fold increased risk for adverse perinatal outcomes. After adjusting for the confounding effects of maternal characteristics and coexisting pregnancy complications, women aged 35–39 years were at increased risk for operative vaginal delivery (adjusted odds ratio [OR] 1.5, 95% confidence interval [CI] 1.2–1.7) and cesarean delivery (adjusted OR 1.6, 95% CI 1.5–1.7), while women aged 40 years and older were at increased risk for preterm delivery (before 37 weeks of gestation) (adjusted OR 1.7, 95% CI 1.3–2.2), operative vaginal delivery (adjusted OR 3.1, 95% CI 2.0–4.6), and cesarean delivery (adjusted OR 2.6, 95% CI 2.2–3.1). In those women who had a completely uncomplicated pregnancy and a normal vaginal delivery, advanced maternal age was still significantly associated with early preterm delivery (before 34 weeks of gestation), a birth weight Conclusion In this population of Taiwanese women, there is an increasing trend in the mean maternal age at the birth of the first child. Furthermore, advanced maternal age is independently associated with specific adverse perinatal outcomes.