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OBJECTIVE Endometriosis and pelvic inflammatory disease are considered to be risk factors for ovarian cancer, as dysbiosis probably contributes to ovarian cancer development via chronic inflammation and immune response alteration. Therefore, we hypothesized that pelvic inflammatory disease predisposes to ovarian cancer development in women with endometriosis. METHODS We selected patients who were diagnosed with endometriosis or pelvic inflammatory disease between January 1, 2000 and December 31, 2015, in a 2 million longitudinal health and welfare database in Taiwan with cancer and death registries. Patients were divided into five groups: (1) those with endometriosis, (2) those with pelvic inflammatory disease, (3) those with endometriosis diagnosed before pelvic inflammatory disease, (4) those with pelvic inflammatory disease diagnosed before endometriosis, and (5) healthy women. Propensity score matching with inverse probability of treatment weighting was used to adjust for covariates across the study groups. RESULTS The risk of ovarian cancer was significantly higher in women with endometriosis and subsequent pelvic inflammatory disease than in those with endometriosis alone (hazard ratio 8.07; 95% confidence interval 4.53-14.37; P

We aim to assess the changes in sexual function and vaginal topography using 3-D transperineal ultrasound in stress-incontinent women treated with Er:YAG vaginal laser. Two hundred and twenty women with stress urinary incontinence (SUI) treated with Er:YAG laser were recruited. Assessment before and 6 months after the treatment included vaginal topography using 3-D transperineal ultrasound and sexual function using female sexual function index questionnaire (FSFI). A total of 50 women with complete data showed that the symptomatic improvement was noted in 37 (74%) women. After Er:YAG vaginal laser treatment, significantly decreased width and cross-sectional area in proximal, middle, and distal vagina were found in women with SUI. Nearly all of the domains of FSFI improved significantly after the vaginal laser treatment, except sexual desire. In conclusion, 3-D transperineal ultrasound can be used to conduct vaginal topography. After Er:YAG vaginal laser treatment, the anatomical changes of vaginal shrinkage and the improvement of female sexual function were both noted. The favorable outcome of sexual function partly related to the tightening of vagina, as evidenced by the measurements of the 3-D transperineal ultrasound.

This paper presents a new learning control structure using fuzzy broad learning system (FBLS) for adaptive model predictive control (AMPC) of nonlinear digital time-delay dynamic systems. The proposed control method, abbreviated as FBLS-ANMPC, is novel in combining FBLS and model predictive control to develop a FBLS-ANMPC control law for high-performance setpoint tracking control and disturbance rejection. Comparative simulations are well used to demonstrate the effectiveness and merits of the proposed method in comparison with five existing methods. Experimental results on temperature control of a heating barrel in a plastic injection molding machine are conducted to show the practicability of the proposed method.

Objective To identify factors associated with voiding dysfunction after Uphold™ transvaginal mesh (TVM) repair in women with pelvic organ prolapse (POP). Study Design We performed a retrospective analysis of 110 women with symptomatic pelvic organ prolapse (POP), anterior vaginal wall prolapse and/or apical prolapse (stage II to IV) who were scheduled for Uphold™ mesh surgery from September 2015 through December 2016. All subjects underwent urinalyses, UDI-6, IIQ-7, ICI-Q, POPDI-6, and pelvic examinations using the POP quantification (POP-Q) staging system before and after surgeries, with follow-up durations ranging from 24−36 months. Results A total of 12 (10.9 %) of 110 women reported voiding dysfunction after Uphold™ mesh surgery. Using univariate analysis, there were no differences in body mass index and urodynamic parameters between normal voiding group and dysfunctional voiding group (P > 0.05). However, in patients aged above 71, POPDI-6 score≧13, preoperative concomitant urinary hesitancy, and incomplete emptying were found to be significant predictors of voiding dysfunction following Uphold™ mesh surgeries (P Conclusion In patients aged above 71, POPDI-6 score≧13, preoperative concomitant urinary hesitancy, and incomplete emptying were significant predictors of voiding dysfunction after Uphold™.

// Yu-Chih Wang 1, * , Cheng-Fang Tsai 2, * , Hsiao-Li Chuang 3 , Yi-Chih Chang 4 , Hung-Sheng Chen 2 , Jau-Nan Lee 1 , Eing-Mei Tsai 1, 2 1 Department of Obstetrics and Gynecology, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan 2 Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan 3 National Applied Research Laboratories, National Laboratory Animal Center, Nangang, Taipei 11529, Taiwan 4 Department of Medical Laboratory Science and Biotechnology, China Medical University, Taichung 40402, Taiwan * These authors contributed equally to this work Correspondence to: Eing-Mei Tsai, email: tsaieing@yahoo.com Keywords: aryl hydrocarbon receptor, sphingosine kinase 1, sphingosine 1-phosphate, sphingosine-1-phosphate receptor 3, breast cancer stem cells Received: December 06, 2015 Accepted: March 28, 2016 Published: April 26, 2016 ABSTRACT Understanding the regulatory mechanisms unique to breast cancer stem cells (BCSCs) is required to control breast cancer metastasis. We found that phthalates promote BCSCs in human breast cancer cell cultures and xenograft tumors. A toxic phthalate, benzyl butyl phthalate (BBP), activated aryl hydrocarbon receptor in breast cancer cells to stimulate sphingosine kinase 1 (SPHK1)/sphingosine 1-phosphate (S1P)/sphingosine-1-phosphate receptor 3 (S1PR3) signaling and enhance formation of metastasis-initiating BCSCs. BBP induced histone modifications in S1PR3 in side population (SP) cells, but not in non-SP cells. SPHK1 or S1PR3 knockdown in breast cancer cells effectively reduced tumor growth and lung metastasis in vivo . Our findings suggest S1PR3 is a determinant of phthalate-driven breast cancer metastasis and a possible therapeutic target for regulating BCSC populations. Furthermore, the association between breast carcinogenesis and environmental pollutants has important implications for public health.

Ovarian cancer is the one of the most lethal gynecological cancer types. MicroRNAs (miRs) are noncoding RNAs that modulate the translation of their target mRNAs via binding to a complementary sequence in the target 3' untranslated region, and the dysregulation of certain miRs has been demonstrated to contribute to cancer progression. In this regard, the current study extended our previous work and used next‑generation sequencing data to search for upstream regulators of genetic alterations that are common in ovarian cancer, as well as the miRs that are involved in controlling the expression of these regulators. An miR prediction program was used to identify miR‑381 as an upstream regulator of phosphatidylinositol 3‑kinase catalytic subunit α (PIK3CA) in the context of ovarian cancer. Levels of miR‑381 were decreased in clear cell and endometrioid carcinoma ovarian cancer. Experimentally induced upregulation of miR‑381 led to a decrease in the level of PIK3CA in ovarian cancer cells. Furthermore, experimentally induced upregulation of miR‑381 inhibited the proliferation of ovarian cancer cells in vitro and their ability to form colonies and migrate. The observed decrease in miR‑381 in ovarian cancer could be reversed upon overexpression of the gene encoding the tumor suppressor homeobox D10. The current results highlight the role of miR‑381‑mediated regulation of PIK3CA in the development and progression of ovarian cancer and suggest that restoration of miR‑381 to normal levels in ovarian cancer cells may constitute a therapeutic strategy for patients.

This work presents a novel particle filter (PF) method to track nonlinear and non-Gaussian dynamic state-space models (DSSMs) for a capacitive touch panel system to achieve an accurate touch position and smooth trajectory when the touch movement changes rapidly with a nonlinear trajectory. Touched positions in the axis-intersect method are also detected using a micro-controller unit (MCU) and a sensor integrated circuit (IC). Additionally, the proposed PF method is designed to achieve the trajectory tracking of calculated positions timely. Experimental results demonstrate that the proposed PF method offers a better root mean square error (RMSE) of linear and nonlinear tracking trajectories than that of the Kalman filter (KF) based on the capacitive touch panel (CTP).

Phthalate, an environmental toxin, has been considered as an endocrine-disrupting chemical. Growing evidence has demonstrated links between endocrine-disrupting chemicals, tissue development, and reproductive physiology, but the mechanisms of gene expression regulation by environmental factors that affect cell differentiation are unclear. Herein, we investigated the effects of butyl benzyl phthalate (BBP) on human endometrial mesenchymal stem/stromal cell (EN-MSC) differentiation and identified a novel signaling pathway. Differentiation of endometrial mesenchymal stem/stromal cells decreased after administration of BBP. We analyzed BBP regulation of gene expression in EN-MSC using cDNA microarrays and Ingenuity Pathway Analysis software to identify affected target genes and their biological functions. PITX2 emerged as a common gene hit from separate screens targeting skeletal and muscular disorders, cell morphology, and tissue development. BBP decreased transcription of PITX2 and elevated expression of the microRNA miR-137, the predicted upstream negative regulator of PITX2. These data indicated that BBP affects PITX2 expression through miR-137 targeting of the 3′ untranslated region of PITX2 mRNA. PITX2 down-regulation also decreased MyoD transcript levels in EN-MSC. Our results demonstrate that BBP decreases EN-MSC myogenic differentiation through up-regulation of miR-137, contribute to our understanding of EN-MSC differentiation, and underline the hazardous potential of environmental hormones.

It is believed that endometrial miRNAs contribute to the aetiology of endometriosis in stem cells; however, the mechanisms remain unclear. Here we collected serum samples from patients with or without endometriosis and characterized the miRNA expression profiles of these two groups. MicroRNA-199a-5p (miR-199a-5p) was dramatically down-regulated in patients with endometriosis compared with control patients. In addition, we found that the tumour suppressor gene, SMAD4, could elevate miR-199a-5p expression in ectopic endometrial mesenchymal stem cells. Up-regulation of miR-199a-5p suppressed cell proliferation, motility and angiogenesis of these ectopic stem cells by targeting the 3' untranslated region of VEGFA. Furthermore, we established an animal model of endometriosis and found that miR-199a-5p could decrease the size of endometriotic lesions in vivo. Taken together, this newly identified miR-199a-5p module provides a new avenue to the understanding of the processes of endometriosis development, especially proliferation, motility and angiogenesis, and may facilitate the development of potential therapeutics against endometriosis.

This work adopts a method to detect the force signal from z-directional with a stylus and finger for capacitive touch panels (CTPs). To obtain the accuracy of force signal, the Kalman filter (KF) is utilized to reduce the noise of force signal. Moreover, the directional weighted method is used to achieve the smooth drawing and stroke reconstruction after processing force signal by the KF algorithm. The experiment results demonstrate the effectiveness of drawing and stroke reconstruction with both stylus and finger.

Endometriosis is the hormone-dependent product of endometrial tissue found outside the uterus. Recently, micro-RNAs (miRNAs) were shown to play a role in endometriotic lesion development. However, the mechanism of steroid hormones responsible for miRNA remains obscure. In the present study, we assayed for the effects of synthetic steroid hormones (danazol, progesterone, and medroxyprogesterone acetate [MPA]) on miRNAs in endometriosis. We used a global miRNA expression profile microarray to evaluate miRNA expression in endometrial mesenchymal stem cells (EN-MSCs) of ovarian endometrioma following treatment with 1 μM danazol, progesterone, or MPA. Furthermore, we selected candidate miRNAs whose expression changed more than fivefold and compared the effects of danazol, progesterone, and MPA treatments and also compared those results with controls in EN-MSCs. Among those with a fivefold change, we found 13 ectopically upregulated miRNAs in EN-MSCs. To understand the function of these 13 miRNAs, we subjected their sequences to Ingenuity Pathway Analysis. According to both the etiology and pathogenesis of endometriosis, we found that miR-199a-5p and miR-34a-5p showed specific association with the disease, including molecular and cellular functions. Steroid hormone treatment elevated the levels of miR-199a-5p and miR-34a-5p. An inhibitor of miR-34a-5p also reduced the synthetic steroid hormones effects on cell proliferation. In vivo data revealed that miRNA levels in endometriotic lesions correlated with findings following in vitro synthetic hormone treatment. Our data show the effects of synthetic steroid hormones on miRNA regulation. These findings contribute to our understanding of the molecular impact of the synthetic steroid hormones and suggest a potential mechanism for endometriosis treatment.

Objectives Adequately addressing the scope of disability in patients with chronic neck pain is crucial in a clinical setting. The aim of this study was to determine the disease profile of patients with chronic neck pain and to analyze the factors related to the level of disability. Methods We studied 121 patients with chronic neck pain. The following data were obtained from the participants: Chinese Health Questionnaire-12, the Pittsburgh Sleep Quality Index, the visual analog scale to pain, pressure pain threshold, the Neck Disability Index, and heart rate variability analysis. Cluster analysis was performed to divide patients into separate groups according to their presentations. A Pearson correlation was computed to analyze factors correlated with disability (Neck Disability Index). The significance level was set at P Results Cluster analysis yielded 3 groups of patients with distinct features. Group I had a sex composition similar to the original population, was younger, and displayed the lowest overall deficits. Group II included middle-to-older-aged women, and presented with a higher level of pain, psychological distress, sleep disorder, and disability. Group III, comprising middle-to-older-aged men, showed moderate symptom severity. Correlation revealed that the factors significantly associated with a high degree of disability were low heart rate variability, high pain intensity, older age, poor sleep quality, and high psychological distress. Discussion We suggest that 3 distinct subgroups of patients with chronic neck pain exhibit particular features. Furthermore, reduced heart rate variability was associated with subjective disability in these patients. Further study is advised to establish the pathologic mechanism and clinical applications of our findings.

Provocative tests are useful in diagnosing biceps tendon tendinitis. This is the first study to establish the reliability of these tests by comparing the resuts with musculoskeletal ultrasound (US) findings. This study examined 125 patients (69 women and 56 men) and 143 shoulders with shoulder pain. Yergason's test, Speed's test and a bicipital groove tenderness test were performed and musculoskeletal US findings were used as standard reference. Biceps tendon tendinitis was diagnosed with US in 39.1% of the patients and, of those, 55.3% had coexisting rotator cuff injury. The sensitivity and specificity of Yergason's test were 32% and 78%, respectively. The sensitivity and specificity of Speed's test were 63% and 58%, respectively. In conclusion, all three tests are limited by poor sensitivity. US can be an image modality choice in diagnosing biceps pathology.

The authors hypothesized that serum retinol-binding protein 4 (RBP4) concentrations will be higher in gestational diabetes mellitus (GDM) subjects. This study tested both women with GDM and healthy pregnant women and correlated their serum RBP4 concentrations with body mass index (BMI) and a variety of other parameters. Also, since there is no information on the relationship between RBP4 concentrations in maternal and fetal serum, this study measured these at delivery and examined whether there were correlations between the cord serum RBP4 levels and maternal serum RBP4 concentrations, neonatal birth weights, and gestational age at delivery. A total of 40 women were evaluated: 20 women with GDM and 20 healthy pregnant women to serve as control subjects. Serum RBP4 concentrations were analyzed with the use of an enzyme-linked immunosorbent assay kit. Serum RBP4 concentrations at glucose challenge test (GCT) were significantly higher in the GDM group (42.4 +/- 13.8 ng/mL) than in the healthy control group (32.0 +/- 8.7 ng/mL; P = .007). BMI at GCT (P = .003) and GDM/no GDM (P = .014) were significantly correlated to serum RBP4 concentrations at GCT by multiple linear regression analysis. In GDM subjects, serum RBP4 concentrations immediately after delivery were significantly lower than those at GCT (30.1 +/- 11.0 ng/mL, 42.4 +/- 13.8 ng/mL; P.001), but there was no such difference in normal subjects (30.9 +/- 10.0 ng/mL, 32.0 +/- 8.7 ng/mL; P = .581). Cord serum RBP4 concentrations were significantly lower than maternal serum RBP4 concentrations at delivery (10.9 +/- 3.8 ng/mL, 30.5 +/- 10.4 ng/mL; P.001). Only fetal birth weight (P = .049) was independently related to cord serum RBP4 concentrations at delivery by multiple linear regression analysis. This study found increased serum RBP4 concentrations at GCT in GDM subjects, and GDM was significantly correlated to serum RBP4 levels after adjustment for the effect of BMI. Lower RBP4 concentrations were found at delivery in GDM subjects. Maternal serum RBP4 concentrations were significantly higher than cord serum RBP4 concentrations, and fetal birth weights were independently correlated to cord serum RBP4 concentrations. These findings may indicate that RBP4 plays a role in the pathogenesis of GDM. However, further experiments are required to clarify this role and find a possible regimen for GDM treatment.

To measure serum resistin levels in infertile women undergoing in vitro fertilisation-embryo transfer (IVF-ET), and to find any correlations between serum resistin levels and body weight, body mass index, the number of oocytes retrieved, and the outcome of IVF-ET. In addition, to assess whether there is any difference in serum resistin levels between infertility caused by polycystic ovary syndrome (PCOS) and infertility caused by other female factors.We designed a case-control study, and a total of 44 infertile women were enrolled. The blood samples for resistin measurement were collected on day 3 of the menstrual cycle prior to the administration of gonadotropin during in vitro fertilisation. These cases were then divided into 2 subgroups (PCOS group versus non-PCOS group) and a number of variables were measured and compared, including serum resistin levels.Serum resistin levels were inversely correlated with the number of oocytes retrieved (r=-0.371, p=0.013). No significant correlation was found between serum resistin levels and body mass index or body weight, either in the whole group or in the 2 subgroups. Serum resistin levels in the non-PCOS group were significantly higher than in the PCOS group (p=0.049). Serum resistin levels in the non-PCOS group were inversely correlated to the number of oocytes retrieved (r=-0.386, p=0.039), but no similar correlation was found in the PCOS group. There was no correlation between serum resistin levels and fertility rate or clinical pregnancy rate in either subgroup.We observed a negative correlation between serum resistin levels and the number of oocytes retrieved during IVF. However, this phenomenon was only present in the non-PCOS group. This result suggests that serum resistin levels might be a good predictor of ovarian response in infertile women without PCOS during IVF. The role of serum resistin in response to inflammation caused by endometriosis or chronic pelvic infection, both of which are major causes of female infertility, should be examined in a further study.

Recent molecular and pathological studies suggest that endometriosis may serve as a precursor of ovarian cancer (endometriosis-associated ovarian cancer, EAOC), especially of the endometrioid and clear cell subtypes. Accordingly, this study had two cardinal aims: first, to obtain mutation profiles of EAOC from Taiwanese patients; and second, to determine whether somatic mutations present in EAOC can be detected in preneoplastic lesions. Formalin-fixed paraffin-embedded (FFPE) tissues were obtained from ten endometriosis patients with malignant transformation. Macrodissection was performed to separate four different types of cells from FFPE sections in six patients. The four types of samples included normal endometrium, ectopic endometriotic lesion, atypical endometriosis, and carcinoma. Ultra-deep (1000×) targeted sequencing was performed on 409 cancer-related genes to identify pathogenic mutations associated with EAOC. The most frequently mutated genes were PIK3CA (6/10) and ARID1A (5/10). Other recurrently mutated genes included ETS1, MLH1, PRKDC (3/10 each), and AMER1, ARID2, BCL11A, CREBBP, ERBB2, EXT1, FANCD2, MSH6, NF1, NOTCH1, NUMA1, PDE4DIP, PPP2R1A, RNF213, and SYNE1 (2/10 each). Importantly, in five of the six patients, identical somatic mutations were detected in atypical endometriosis and tumor lesions. In two patients, genetic alterations were also detected in ectopic endometriotic lesions, indicating the presence of genetic alterations in preneoplastic lesion. Genetic analysis in preneoplastic lesions may help to identify high-risk patients at early stage of malignant transformation and also shed new light on fundamental aspects of the molecular pathogenesis of EAOC.Molecular characterization of endometriosis-associated ovarian cancer genes by targeted NGS. Candidate genes predictive of malignant transformation were identified. Chromatin remodeling, PI3K-AKT-mTOR, Notch signaling, and Wnt/β-catenin pathway may promote cell malignant transformation.

Thrombotic thrombocytopenic purpura (TTP) and hemolytic uremic syndrome (HUS) are rare and closely related disorders characterized by microangiopathic hemolytic anemia, thrombocytopenia, and renal failure. Many risk factors have been reported including infection, cancer, pregnancy, a variety of drugs (e.g. anticancer drugs), and autoimmune diseases. The incidence of TTP-HUS is higher in females than in males, especially during pregnancy and the immediate postpartum period. Review of the literature reveals that delayed postpartum hemorrhage is a rare clinical presentation of TTP-HUS. We report a case of TTP-HUS with recurrent delayed postpartum hemorrhage and dismal outcome.

Fourteen women with placenta praevia (including one who also had placenta accreta) undergoing caesarean section had massive bleeding after removal of the placenta. In order to preserve the uterus, two parallel vertical compression sutures were placed in the lower segment to compress the anterior and posterior walls of the lower uterine segment. The haemorrhage from the lower segment stopped immediately after the knots were tightened. All women later resumed normal menstrual flow with no apparent complications. Two of the 14 women had a spontaneous pregnancy one to two years after the operation. This parallel vertical compression suturing technique is simple, easy and effective for controlling bleeding in women with placenta praevia or accreta. We suggest that this technique be tried first before other more complex procedures are undertaken.

Summary Objective To evaluate the clinical value of human papillomavirus (HPV) DNA testing (Hybrid Capture II) in predicting which women with mild cervical cytologic abnormality (atypical squamous cells of undetermined significance [ASCUS] or low-grade squamous intraepithelial lesions [LSIL]) are most likely to have high-grade cervical intraepithelial neoplasia (CIN). Materials and Methods A total of 266 women with mildly abnormal Papanicolaou (Pap) smear results (160 with ASCUS and 106 with LSIL) concurrently underwent Hybrid Capture II testing, repeat Pap smear, and colposcopy-directed biopsies. Results Overall, the underlying prevalence of histologically confirmed CIN2/3 was 16.9% (27/160) in women with ASCUS and 29.2% (31/106) in those with LSIL. High-risk HPV DNA was detected in 55% and 88.7%, respectively. The sensitivity of CIN2/3 detection by HPV DNA was 96.3% (26/27) and 100% (31/31) among women with ASCUS and LSIL, respectively. Conclusion A positive baseline HPV test in women with ASCUS or LSIL is clinically equivalent, requiring colposcopic examination and denoting an approximately one-third chance of having CIN2/3. Among women with ASCUS, a negative HPV test strongly indicates that the patient is free of CIN2/3, which should minimize a patient's anxiety and unnecessary colposcopic examinations.

Implantation of a pregnancy within the scar of a previous cesarean delivery is the rarest of ectopic pregnancy locations, with only 32 cases reported in the English-language medical literature. A 28-year-old woman was admitted to our institution with a suspected ectopic pregnancy located in the scar from a previous cesarean section. Ultrasound revealed a well-encapsulated, bulging mass with a gestational sac within the anterior uterine isthmus in the site of an old cesarean delivery scar. Laparoscopy was performed to confirm the diagnosis, and the gestational products also were removed laparoscopically. The defect in the uterus was then repaired by suturing. Total operative time was 120 minutes, blood loss was limited, and no transfusion was needed. Laparoscopy may be a reasonable alternative to laparotomy for an unruptured ectopic pregnancy in a cesarean scar.

Objective. To explore the possibility of using early second trimester amniotic fluid leptin levels as a predictor of pregnancy outcome in twin pregnancy. Study design. Amniotic fluid leptin levels from 18 twin-pregnant women in early second trimester were analyzed for their correlation with gestational age at delivery and fetal birthweight. Leptin levels in 16 amniotic fluid samples collected from small for gestational age (SGA) twin pregnancies were compared with those in 20 amniotic fluid samples collected from non-SGA twin pregnancies. Results. A significant correlation was observed between amniotic fluid leptin levels and gestational age at delivery ( r = 0.71, p < 0.001) as well as fetal birthweight ( r = 0.72, p < 0.001). There was also a significant correlation between gestational age at delivery and fetal birthweight ( r = 0.92, p < 0.001). The average gestational age at delivery was 30.4 ± 1.4 weeks in the SGA group, with a mean birthweight of 1552 ± 200 g at delivery. For the non-SGA group, the ...

Objective. To measure adiponectin levels in maternal serum and umbilical cord serum at delivery, and examine whether or not there are correlations between adiponectin levels and neonatal birthweights, maternal body weights and body mass indexes. Study design. The study included 84 healthy mothers who had given birth to healthy neonates. Adiponectin levels in maternal serum and umbilical cord serum were determined by radioimmunoassay and compared. Results. The ranges of adiponectin levels for umbilical cord serum and maternal serum were 22.7-78.4 µg/ml and 4.0-43.3 µg/ml, respectively. Umbilical serum adiponectin levels (46.9 ± 1.2 µg/ml) were significantly higher than maternal serum adiponectin levels (16.1 ± 0.8 µg/ml) ( p < 0.001). No correlation was found between the adiponectin levels in maternal serum and those in umbilical cord serum ( r = 0.158, p = 0.151). Umbilical serum adiponectin levels were significantly correlated with both neonatal birthweights ( r = 0.454, p < 0.001) and gestational ages a...

Understanding the mechanisms in the generation of neural stem cells from pluripotent stem cells is a fundamental step towards successful management of neurodegenerative diseases in translational medicine. Albeit all-trans retinoic acid (RA) has been associated with axon outgrowth and nerve regeneration, the maintenance of differentiated neurons, the association with degenerative disease like Parkinson's disease, and its regulatory molecular mechanism from pluripotent stem cells to neural stem cells remain fragmented. We have previously reported that RA is capable of differentiation of human trophoblast stem cells to dopamine (DA) committed progenitor cells. Intracranial implantation of such neural progenitor cells into the 6-OHDA-lesioned substantia nigra pars compacta successfully regenerates dopaminergic neurons and integrity of the nigrostriatal pathway, ameliorating the behavioral deficits in the Parkinson’s disease rat model. Here, we demonstrated a dynamic molecular network in systematic analysis by addressing spatiotemporal molecular expression, intracellular protein-protein interaction and inhibition, imaging study, and genetic expression to explore the regulatory mechanisms of RA induction in the differentiation of human trophoblast stem cells to DA committed progenitor cells. We focused on the tyrosine receptor kinase (Trk), G proteins, canonical Wnt2B/β-catenin, genomic and non-genomic RA signaling transductions with Tyrosine hydroxylase (TH) gene expression as the differentiation endpoint. We found that at the early stage, integration of TrkA and G protein signalings aims for axonogenesis and morphogenesis, involving the novel RXRα/Gαq/11 and RARβ/Gβ signaling pathways. While at the later stage, five distinct signaling pathways together with epigenetic histone modifications emerged to regulate expression of TH, a precursor of dopamine. RA induction generated DA committed progenitor cells in one day. Our results provided substantial mechanistic evidence that human trophoblast stem cell-derived neural stem cells can potentially be used for neurobiological study, drug discovery, and as an alternative source of cell-based therapy in neurodegenerative diseases like Parkinson’s disease.

Surgical technique and instrumentation of laparoscopic lymphadenectomy continue to undergo improvements. A major concern, however, is whether or not the retroperitoneum is adequately exposed. We developed a technique using straight needles to suspend the round ligament and posterior peritoneum. It gives good exposure with little injury to surrounding tissues. The procedure is easy to perform and requires only 3 to 5 minutes, making laparoscopic lymphadenectomy easier.

Purpose: This study was to examine the serum leptin levels in the prediction of pregnancy outcomes in women receiving ovarian hyperstimulation. Effect of leptin on the steroidogenesis was evaluated for granulosa cell (GC) culture in vitro. Method: Serum levels of leptin and estradiol were measured on Day 2, the time of hCG administration and oocyte retrieval in 50 women undergoing long-course GnRH agonist ovarian hyperstimulation. The production of estrogen and progesterone in granulosa cell culture were detected after administration of leptin at the absence or presence of FSH 1 mIU. Results: Leptin levels at the time of hCG injection were significantly lower in the pregnant women than in those without pregnancy. Estradiol concentrations were not correlated with leptin levels during the time of hCG injection and oocyte retrieval. High leptin concentration suppressed both basal estradiol and progesterone productions in GC. Leptin in high doses suppressed estradiol production, but did not alter progesterone production of GC in the presence of FSH. Conclusions: Serum leptin levels may be predictive of IVF pregnancy outcome with the effect on intraovarian progesterone/estradiol ratio during the follicular phase. Significantly low serum leptin levels were noted in the pregnant women than in the nonpregnant women.

Frozen shoulder, or adhesive capsulitis, is a disease of chronic inflammation and fibrosis involving the shoulder joints. The disease is challenging in clinical practice due to painful treatment course, with disease evolution usually lasting weeks or even months, causing significant discomfort and functional loss. Botulinum toxin (BTX) has been discovered to possess abilities in pain management at various clinical diseases. The actual mechanism is still under investigation, and involves inhibition of neurotransmitter release. In addition, BTX is also found to retard process of fibrosis, which is also a key issue in pathogenesis of frozen shoulder. Therefore, we hypothesize that intra-articular injection of BTX can be an effective alternative for treatment of frozen shoulder.

Objective: The purpose of this study was to evaluate the feasibility of the use of deoxyribonucleic acid microsatellite alterations in cervical epithelia in the prediction of high-grade dysplasia and to compare it with a strategy based on human papillomavirus testing. Study Design: Our prospective study subjects were from a cohort of 498 women with minimally abnormal Papanicolaou test results including atypical squamous cells of undetermined significance and low-grade squamous intraepithelial lesion who had documented repeated Papanicolaou and human papillomavirus tests. Of these, 52 eligible patients having conizations or hysterectomies as their histologic outcomes were subjected to tests of loss of heterozygosity on a panel of 5 microsatellites (D3S1110, THRB, D3S1228, D6S291, D3S1289) within the deoxyribonucleic acid of exfoliated cervical epithelia. These genetic alterations were analyzed through fluorescence polymerase chain reaction by comparison of allele ratios of exfoliated cells with those of normal control tissue. Predictive values for high-grade cervical dysplasia and cancer between this deoxyribonucleic acid marker and human papillomavirus status were compared. Results: With the use of loss of heterozygosity in at least one locus for predicting high-grade cervical neoplastic lesion, the sensitivity, specificity, positive predictive value, and negative predictive value were 96.7%, 59.1%, 76.3%, and 92.9%, which were superior to those of the human papillomavirus test (80%, 59.1%, 72.7%, and 92.9%). As a triage for atypical squamous cells of undetermined significance, its sensitivity and negative predictive value were up to 100%. Conclusion: The promising results on determining microsatellite alteration in dysplastic lesions might imply that it is possible to detect the earliest changes by potential molecular markers with exfoliated cervical epithelial cells. (Am J Obstet Gynecol 2001;185:108-15.)

Tranexamic acid is commonly used to treat various kinds of bleeding disorders. It has been shown to cause severe convulsions in animal experiments. We report a patient who experienced a single convulsive seizure that resulted in transient hyperammonemia during treatment with tranexamic acid. A 68-year-old man was admitted and received tranexamic acid for persistent hemoptysis. After 5 days of admission, clonic convulsions that progressed to generalized seizures were noted following the intravenous administration of the tranexamic acid. Elevated ammonia level (233 μmol/l) was found. No further seizures occurred after immediate discontinuation of the drug. No other cause of seizures was found. The ammonia level on the following day normalized even without any treatment for the hyperammonemia. This case highlights that generalized convulsion is a very rare, but serious adverse effect of tranexamic acid. Generalized convulsion should be considered as a potential cause of transient hyperammonemia.

It is believed that endometrial miRNAs contribute to the aetiology of endometriosis in stem cells; however, the mechanisms remain unclear. Here we collected serum samples from patients with or without endometriosis and characterized the miRNA expression profiles of these two groups. MicroRNA-199a-5p (miR-199a-5p) was dramatically down-regulated in patients with endometriosis compared with control patients. In addition, we found that the tumour suppressor gene, SMAD4, could elevate miR-199a-5p expression in ectopic endometrial mesenchymal stem cells. Up-regulation of miR-199a-5p suppressed cell proliferation, motility and angiogenesis of these ectopic stem cells by targeting the 3' untranslated region of VEGFA. Furthermore, we established an animal model of endometriosis and found that miR-199a-5p could decrease the size of endometriotic lesions in vivo. Taken together, this newly identified miR-199a-5p module provides a new avenue to the understanding of the processes of endometriosis development, especially proliferation, motility and angiogenesis, and may facilitate the development of potential therapeutics against endometriosis.

This paper reports the results of an investigation of hot-carrier effects on analog performance in LATID (Large-Angle-Tilt-Implanted-Drain) and conventional LDD submicron CMOS technology. The investigation focuses on hot-carrier induced degradation of voltage gain, degradation of drain output resistance, and drift of offset voltage of differential pairs. Results illustrate that LATID technology significantly out-performs LDD technology in regard to hot-carrier immunity of key analog parameters in short channel length devices as well as in relatively long channel length devices. The improvement of analog hot-carrier immunity with LATID is attributed to the mechanisms of reduction and departure of high electrical field from the drain area. Results suggest that LATID technology is a promising candidate for mixed-signal ULSI applications.

Phthalates—substances used in the manufacture of plastics—are considered as possible human carcinogens and tumor-promoting agents. The worldwide annual production of plastics surpassed 300 million tons in 2010. Plastics are an indispensable material in modern society, and many products manufactured from plastics are a boon to public health; however, plastics also pose health risks. Animal studies have indicated that phthalates are carcinogenic, but human epidemiological data confirming this carcinogenicity in humans are limited. The activation of peroxisome proliferator-activated receptor α (PPARα), which has been observed in rodent carcinogenesis, has not been observed in humans. Here, we review the hypothesis that the aryl hydrocarbon receptor (AhR) and its downstream signaling cascade promote phthalate-induced tumorigenesis.

Objective To describe resectoscopic treatment with vasopressin injection as an effective surgical intervention for ectopic pregnancy in previous cesarean delivery scar (PCDS) defect. Design Case report. Setting University hospital. Patient(s) Two women with ectopic pregnancy in PCDS defect. Intervention(s) The patients underwent transvaginal ultrasound examination, followed by operative hysteroscopy with vasopressin injection for evacuating the ectopic pregnancy in PCDS defect. Main Outcome Measure(s) Conservation of the uterus. Result(s) Successful resectoscopic treatment of ectopic pregnancy in PCDS defect. Conclusion(s) Resectoscopic treatment of ectopic pregnancy in PCDS defect is a safe and efficient technique that has the advantage of a rapid return to normal levels of β-hCG. Intracervical vasopressin administration could decrease intraoperative bleeding and provide a clear view during the operation.

We investigated the signaling pathway of the arylhydrocarbon receptor (AhR) on HO23 cells (immortalized human granulosa cells (hGC)) mediated by benzyl butyl-phthalate (BBP). BBP (1 μM) significantly increased the mRNA and protein levels of AhR, aryl hydrocarbon receptor nuclear translocator (ARNT) and cytochrome-P450 (CYP)1B1 in HO23 cells. Treatment with 3',4'-dimethoxyflavone (3',4'-DMF) or AhR siRNA significantly reduced AhR and CYP1B1, but CYP1A1 was not affected by 3',4'-DMF or AhR siRNA, suggesting that increases in CYP1A1 may not regulated by AhR. BBP induced the AhR fusion protein to localize and accumulate around the nucleus, and AhR heterodimerization with ARNT was observed in the nucleus by immunoprecipitation. Chromatin immunoprecipitation and reporter assays revealed the effect of BBP on CYP1B1, but not CYP1A1. Necrosis was significantly increased in HO23 cells after BBP treatment, and 3',4'-DMF, AhR siRNA or CYP1B1 siRNA knockdown blocked this phenomenon. These data suggest that BBP-induced HO23 cell necrosis is AhR and CYP1B1 dependent.

Background Cancer cells are believed to arise primarily from stem cells. CD44+/CD24- have been identified as markers for human breast cancer stem cells. Although, HER2 is a well known breast cancer oncogene, the mechanisms of action of this gene are not completely understood. Previously, we have derived immortal (M13SV1), weakly tumorigenic (M13SV1R2) and highly tumorigenic (M13SV1R2N1) cell lines from a breast epithelial cell type with stem cell phenotypes after successive SV40 large T-antigen transfection, X-ray irradiation and ectopic expression of HER2/C-erbB2/neu. Recently, we found that M13SV1R2 cells became non-tumorigenic after growing in a growth factor/hormone-deprived medium (R2d cells). Results In this study, we developed M13SV1R2N1 under the same growth factor/hormone-deprived condition (R2N1d cells). This provides an opportunity to analyze HER2 effect on gene expression associated with tumorigenesis by comparative study of R2d and R2N1d cells with homogeneous genetic background except HER2 expression. The results reveal distinct characters of R2N1d cells that can be ascribed to HER2: 1) development of fast-growing tumors; 2) high frequency of CD44+/CD24- cells (~50% for R2N1d vs. ~10% for R2d); 3) enhanced expression of COX-2, HDAC6 mediated, respectively, by MAPK and PI3K/Akt pathways, and many genes associated with inflammation, metastasis, and angiogenesis. Furthermore, HER2 expression can be down regulated in non-adhering R2N1d cells. These cells showed longer latent period and lower rate of tumor development compared with adhering cells. Conclusions HER2 may induce breast cancer by increasing the frequency of tumor stem cells and upregulating the expression of COX-2 and HDAC6 that play pivotal roles in tumor progression.

Objective To elucidate the role of endometrial stem-progenitor cells in the etiology of endometriosis and to develop an animal model to study the invasion ability of endometrial cells. Design Gene expression and cell function studies were designed. Setting Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan. Patient(s) Human endometrial mesenchymal stem cells (MSCs) were isolated from 22 different endometrium biopsies after surgery for treatment of endometriosis. Intervention(s) Endometrial MSCs developed from eutopic and ectopic endometrial tissues. Main Outcome Measure(s) Characterization of MSC phenotypes (i.e., differentiation induction and gene expression by flow cytometric analysis); comparative study of cell functions (i.e., cell growth, migration, and invasion assays). The invasion of implants in an animal model was examined by histologic staining. Result(s) We compared the characteristics of eutopic and ectopic endometrial MSCs from the same endometrial donor. Although both showed similar mesenchymal cell phenotypes, ectopic endometrial MSCs showed distinctly greater ability of cell migration and invasion. Furthermore, in an in vivo cell invasion model using cells grown in scaffold and transplantation in immune-deficient mice, the ectopic endometrial MSCs were found to form many new blood vessels and to invade surrounding tissue. Conclusion(s) These results indicate unique invasion and angiogenesis characteristics of ectopic endometrial MSCs that may underlie the pathogenesis of ectopic endometriosis. The animal invasion model will be useful for future characterization of endometrial MSCs.

The statistical variation of the threshold voltage induced by random distributed device parameters is examined in both bulk and SOI MOSFETs. Our study reveals that the threshold voltage of thin-film SOI MOSFETs is less sensitive to inherent fluctuations in device parameters. Design considerations in minimizing the statistical threshold voltage variation in SOI MOSFETs are discussed. By proper choice of the gate material, film thickness and channel doping density, enhancement of the production yield can be expected for high-performance SOI VLSI circuits.