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This work fabricates a fishnet grating by exerting two one-dimensional (1D) holographic interference fields with mutually orthogonal grating vectors separately on the substrates of a dye-doped liquid crystal (DDLC) cell. The DDLC mixture in the cell includes a nematic LC, methyl red (MR) dye, and 4-methoxyazobenzene (4MAB) dye. The fishnet grating is formed because the periodical adsorption of the MR dye on the irradiated surfaces of the cell causes the anisotropic photoalignment of the LC. The fishnet grating can be erased (recovered) by the illumination of a UV (green) beam since the trans→cis (cis→trans) isomerization of the 4MAB dye causes the isothermal nematic → isotropic (isotropic → nematic) phase transition of the LC. Such a grating can be used to develop optically controllable photonic crystals. Simulated results depict that a photoresist-coated plastic substrate that is exposed to the fishnet pattern of a 2D grating can be used to develop terahertz fishnet metamaterials, and their resonance spectra can be passively tuned by moving the substrate and lens that forms the fishnet pattern during fabrication. Therefore, the mask-free photolithography can be used to fabricate passively tunable terahertz filters. [ABSTRACT FROM AUTHOR]

Internal hernias are an uncommon cause of small bowel obstruction and present a challenging clinical diagnostic scenario. They result from the abnormal protrusion of an abdominal organ through a peritoneal defect and can cause intermittent obstructive symptoms, diffuse abdominal discomfort, and postprandial pain. Paraduodenal hernias comprise 53% of all internal hernias 1 and occur due to failure of the fixation of either the left or transverse mesocolon to the posterior abdominal wall. Its relative rarity results in mortality between 20 and 50% 2 because of delayed diagnosis and consequent obstruction, strangulation, and bowel ischemia. Our case series describes three patients before and after operative fixation of paraduodenal hernia. Only one of the three was identified by preoperative radiologist interpretation. Subsequent diagnosis and definitive treatment were completed by surgical staff to resolve undiagnosed undulating abdominal pain and obstructive-type symptoms. We further analyze left-sided paraduodenal hernias after laparoscopic and robotic repair to define common symptomatology, typical CT findings, and preferred laparoscopic repair techniques.

When a newborn infant has been pushed from the birth canal due to ventilation failure while using a resuscitation mask, the doctor must implement infant intubation and other emergency steps to keep the baby alive. However, due to the excessively small mouth area of a newborn or premature infant, the doctors are unable to view the glottis entrance, which can lead to either a failed intubation or longer intubation time, thereby resulting in either a drop in oxygen levels or a rise in intrathoracic pressure. Although the normal video laryngoscope with a 12mm metal blade certainly improves this type of difficult intubation, nevertheless, doctors often complain that the depth of field (DOF) is insufficient and the width of the blade is too wide when performing intubation on neonatal patients. Therefore, this study aims to develop two modules of infant’s video laryngoscope, an ultra-thin 7mm metal blade and an optical imaging system, the core technology of which includes an optical design of a 2.5mm lens and verifications of imaging quality. In order to allow physicians to determine the infant’s airway position immediately and to avoid the binocular disparity from a physician while giving intubation, this study has simulated the optical properties of monolithic lenses while designing the imaging system, allowing the doctor to have a clearer and undistorted image within the field of view.

Abstract Background Zerumbone, a sesquiterpene compound isolated from subtropical ginger, Zingiber zerumbet Smith, has been documented to exert antitumoral and anti- inflammatory activities. In this study, we demonstrate that zerumbone induces apoptosis in human glioblastoma multiforme (GBM8401) cells and investigate the apoptotic mechanism. Methods We added a caspase inhibitor and transfected wild-type (WT) IKK and Akt into GBM 8401 cells, and measured cell viability and apoptosis by MTT assay and flow cytometry. By western blotting, we evaluated activation of caspase-3, dephosphorylation of IKK, Akt, FOXO1 with time, and change of IKK, Akt, and FOXO1 phosphorylation after transfection of WT IKK and Akt. Results Zerumbone (10∽50 μM) induced death of GBM8401 cells in a dose-dependent manner. Flow cytometry studies showed that zerumbone increased the percentage of apoptotic GBM cells. Zerumbone also caused caspase-3 activation and poly (ADP-ribose) polymerase (PARP) production. N-benzyloxycarbonyl -Val-Ala-Asp- fluoromethylketone (zVAD-fmk), a broad-spectrum caspase inhibitor, hindered zerumbone-induced cell death. Transfection of GBM 8401 cells with WT IKKα inhibited zerumbone-induced apoptosis, and zerumbone significantly decreased IKKα phosphorylation levels in a time-dependent manner. Similarly, transfection of GBM8401 cells with Akt suppressed zerumbone-induced apoptosis, and zerumbone also diminished Akt phosphorylation levels remarkably and time-dependently. Moreover, transfection of GBM8401 cells with WT IKKα reduced the zerumbone-induced decrease in Akt and FOXO1 phosphorylation. However, transfection with WT Akt decreased FOXO1, but not IKKα, phosphorylation. Conclusion The results suggest that inactivation of IKKα, followed by Akt and FOXO1 phosphorylation and caspase-3 activation, contributes to zerumbone-induced GBM cell apoptosis.

Abstract Background Usually patients receive healthcare services from multiple hospitals, and consequently their healthcare data are dispersed over many facilities’ paper and electronic-based record systems. Therefore, many countries have encouraged the research on data interoperability, access, and patient authorization. This study is an important part of a national project to build an information exchange environment for cross-hospital digital medical records carried out by the Department of Health (DOH) of Taiwan in May 2008. The key objective of the core project is to set up a portable data exchange environment in order to enable people to maintain and own their essential health information. This study is aimed at exploring the factors influencing behavior and adoption of USB-based Personal Health Records (PHR) in Taiwan. Methods Quota sampling was used, and structured questionnaires were distributed to the outpatient department at ten medical centers which participated in the DOH project to establish the information exchange environment across hospitals. A total of 3000 questionnaires were distributed and 1549 responses were collected, out of those 1465 were valid, accumulating the response rate to 48.83%. Results 1025 out of 1465 respondents had expressed their willingness to apply for the USB-PHR. Detailed analysis of the data reflected that there was a remarkable difference in the “usage intention” between the PHR adopters and non-adopters (χ2 =182.4, p Conclusions Higher Usage Intentions, Perceived Usefulness and Subjective Norm of patients were found to be the key factors influencing PHR adoption. Thus, we suggest that government and hospitals should promote the potential usefulness of PHR, and physicians should encourage patients' to adopt the PHR.

Abstract Background Previous studies reported divergent results on nutraceutical actions and free radical scavenging capability of ginseng extracts. Variations in ginsenoside profile of ginseng due to different soil and cultivating season may contribute to the inconsistency. To circumvent this drawback, we assessed the effect of major ginsenoside-Rg1 (Rg1) on skeletal muscle antioxidant defense system against exhaustive exercise-induced oxidative stress. Methods Forty weight-matched rats were evenly divided into control (N = 20) and Rg1 (N = 20) groups. Rg1 was orally administered at the dose of 0.1 mg/kg bodyweight per day for 10-week. After this long-term Rg1 administration, ten rats from each group performed an exhaustive swimming, and remaining rats considered as non-exercise control. Tibialis anterior (TA) muscles were surgically collected immediately after exercise along with non-exercise rats. Results Exhaustive exercise significantly (p Conclusions This study provide compelling evidences that Rg1 supplementation can strengthen antioxidant defense system in skeletal muscle and completely attenuate the membrane lipid peroxidation induced by exhaustive exercise. Our findings suggest that Rg1 can use as a nutraceutical supplement to buffer the exhaustive exercise-induced oxidative stress.

Abstract Background Apathy is frequently observed in numerous neurological disorders, including Alzheimer's and Parkinson's, as well as neuropsychiatric disorders including schizophrenia. Apathy is defined as a lack of motivation characterized by diminished goal-oriented behavior and self-initiated activity. This study evaluated a chronic restraint stress (CRS) protocol in modeling apathetic behavior, and determined whether administration of an anticholinesterase had utility in attenuating CRS-induced phenotypes. Methods We assessed behavior as well as regional neuronal activity patterns using FosB immunohistochemistry after exposure to CRS for 6 h/d for a minimum of 21 d. Based on our FosB findings and recent clinical trials, we administered an anticholinesterase to evaluate attenuation of CRS-induced phenotypes. Results CRS resulted in behaviors that reflect motivational loss and diminished emotional responsiveness. CRS-exposed mice showed differences in FosB accumulation, including changes in the cholinergic basal forebrain system. Facilitating cholinergic signaling ameliorated CRS-induced deficits in initiation and motivational drive and rescued immediate early gene activation in the medial septum and nucleus accumbens. Conclusions Some CRS protocols may be useful for studying deficits in motivation and apathetic behavior. Amelioration of CRS-induced behaviors with an anticholinesterase supports a role for the cholinergic system in remediation of deficits in motivational drive.

Abstract Purpose This work aimed to investigate the effect of costunolide, a sesquiterpene lactone isolated from Michelia compressa, on cell cycle distribution and radiosensitivity of human hepatocellular carcinoma (HCC) cells. Methods The assessment used in this study included: cell viability assay, cell cycle analysis by DNA histogram, expression of phosphorylated histone H3 (Ser 10) by flow cytometer, mitotic index by Liu's stain and morphological observation, mitotic spindle alignment by immunofluorescence of alpha-tubulin, expression of cell cycle-related proteins by Western blotting, and radiation survival by clonogenic assay. Results Our results show that costunolide reduced the viability of HA22T/VGH cells. It caused a rapid G2/M arrest at 4 hours shown by DNA histogram. The increase in phosphorylated histone H3 (Ser 10)-positive cells and mitotic index indicates costunolide-treated cells are arrested at mitosis, not G2, phase. Immunofluorescence of alpha-tubulin for spindle formation further demonstrated these cells are halted at metaphase. Costunolide up-regulated the expression of phosphorylated Chk2 (Thr 68), phosphorylated Cdc25c (Ser 216), phosphorylated Cdk1 (Tyr 15) and cyclin B1 in HA22T/VGH cells. At optimal condition causing mitotic arrest, costunolide sensitized HA22T/VGH HCC cells to ionizing radiation with sensitizer enhancement ratio up to 1.9. Conclusions Costunolide could reduce the viability and arrest cell cycling at mitosis in hepatoma cells. Logical exploration of this mitosis-arresting activity for cancer therapeutics shows costunolide enhanced the killing effect of radiotherapy against human HCC cells.

Abstract Background Investigation of metagenomes provides greater insight into uncultured microbial communities. The improvement in sequencing technology, which yields a large amount of sequence data, has led to major breakthroughs in the field. However, at present, taxonomic binning tools for metagenomes discard 30-40% of Sanger sequencing data due to the stringency of BLAST cut-offs. In an attempt to provide a comprehensive overview of metagenomic data, we re-analyzed the discarded metagenomes by using less stringent cut-offs. Additionally, we introduced a new criterion, namely, the evolutionary conservation of adjacency between neighboring genes. To evaluate the feasibility of our approach, we re-analyzed discarded contigs and singletons from several environments with different levels of complexity. We also compared the consistency between our taxonomic binning and those reported in the original studies. Results Among the discarded data, we found that 23.7 ± 3.9% of singletons and 14.1 ± 1.0% of contigs were assigned to taxa. The recovery rates for singletons were higher than those for contigs. The Pearson correlation coefficient revealed a high degree of similarity (0.94 ± 0.03 at the phylum rank and 0.80 ± 0.11 at the family rank) between the proposed taxonomic binning approach and those reported in original studies. In addition, an evaluation using simulated data demonstrated the reliability of the proposed approach. Conclusions Our findings suggest that taking account of conserved neighboring gene adjacency improves taxonomic assignment when analyzing metagenomes using Sanger sequencing. In other words, utilizing the conserved gene order as a criterion will reduce the amount of data discarded when analyzing metagenomes.

Abstract Background Intracranial pediatric germ cell tumors (GCTs) are rare and heterogeneous neoplasms and vary in histological differentiation, prognosis and clinical behavior. Germinoma and mature teratoma are GCTs that have a good prognosis, while other types of GCTs, termed nongerminomatous malignant germ cell tumors (NGMGCTs), are tumors with an intermediate or poor prognosis. The second group of tumors requires more extensive drug and irradiation treatment regimens. The mechanisms underlying the differences in incidence and prognosis of the various GCT subgroups are unclear. Results We identified a distinct mRNA profile correlating with GCT histological differentiation and prognosis, and also present in this study the first miRNA profile of pediatric primary intracranial GCTs. Most of the differentially expressed miRNAs were downregulated in germinomas, but miR-142-5p and miR-146a were upregulated. Genes responsible for self-renewal (such as POU5F1 (OCT4), NANOG and KLF4) and the immune response were abundant in germinomas, while genes associated with neuron differentiation, Wnt/β-catenin pathway, invasiveness and epithelial-mesenchymal transition (including SNAI2 (SLUG) and TWIST2) were abundant in NGMGCTs. Clear transcriptome segregation based on patient survival was observed, with malignant NGMGCTs being closest to embryonic stem cells. Chromosome copy number variations (CNVs) at cytobands 4q13.3-4q28.3 and 9p11.2-9q13 correlated with GCT malignancy and clinical risk. Six genes (BANK1, CXCL9, CXCL11, DDIT4L, ELOVL6 and HERC5) within 4q13.3-4q28.3 were more abundant in germinomas. Conclusions Our results integrate molecular profiles with clinical observations and provide insights into the underlying mechanisms causing GCT malignancy. The genes, pathways and microRNAs identified have the potential to be novel therapeutic targets.

Abstract In the present study, we explore the role of apoptosis signal-regulating kinase 1 (ASK1) in denbinobin-induced apoptosis in human lung adenocarcinoma (A549) cells. Denbinobin-induced cell apoptosis was attenuated by an ASK1 dominant-negative mutant (ASK1DN), two antioxidants (N-acetyl-L-cysteine (NAC) and glutathione (GSH)), a c-Jun N-terminal kinase (JNK) inhibitor (SP600125), and an activator protein-1 (AP-1) inhibitor (curcumin). Treatment of A549 cells with denbinobin caused increases in ASK1 activity and reactive oxygen species (ROS) production, and these effects were inhibited by NAC and GSH. Stimulation of A549 cells with denbinobin caused JNK activation; this effect was markedly inhibited by NAC, GSH, and ASK1DN. Denbinobin induced c-Jun phosphorylation, the formation of an AP-1-specific DNA-protein complex, and Bim expression. Bim knockdown using a bim short interfering RNA strategy also reduced denbinobin-induced A549 cell apoptosis. The denbinobin-mediated increases in c-Jun phosphorylation and Bim expression were inhibited by NAC, GSH, SP600125, ASK1DN, JNK1DN, and JNK2DN. These results suggest that denbinobin might activate ASK1 through ROS production to cause JNK/AP-1 activation, which in turn induces Bim expression, and ultimately results in A549 cell apoptosis.

Abstract Background Analyzing gene expression data by assessing the significance of pre-defined gene sets, rather than individual genes, has become a main approach in microarray data analysis and this has promisingly derive new biological interpretations of microarray data. However, the detection power of conventional gene list or gene set-based approaches is limited on highly heterogeneous samples, such as tumors. Results We developed a novel method, the regulatory event-based Gene Set Analysis (eGSA), which considers not only the consistently changed genes but also every gene regulation (event) of each sample to overcome the detection limit. In comparison with conventional methods, eGSA can detect functional changes in heterogeneous samples more precisely and robustly. Furthermore, by utilizing eGSA, we successfully revealed novel functional characteristics and potential mechanisms of very early hepatocellular carcinoma (HCC). Conclusion Our study creates a novel scheme to directly target the major cellular functional changes in heterogeneous samples. All potential regulatory routines of a functional change can be further analyzed by the regulatory event frequency. We also provide a case study on early HCCs and reveal a novel insight at the initial stage of hepatocarcinogenesis. eGSA therefore accelerates and refines the interpretation of heterogeneous genomic data sets in the absence of gene-phenotype correlations.

Abstract Background Alternative RNA splicing greatly increases proteome diversity and thereby contribute to species- or tissue-specific functions. The possibility to study alternative splicing (AS) events on a genomic scale using splicing-sensitive microarrays, including the Affymetrix GeneChip Exon 1.0 ST microarray (exon array), has appeared very recently. However, the application of this new technology is hindered by the lack of free and user-friendly software devoted to these novel platforms. Results In this study we present a Java-based freeware, easyExon http://microarray.ym.edu.tw/easyexon, to process, filtrate and visualize exon array data with an analysis pipeline. This tool implements the most commonly used probeset summarization methods as well as AS-orientated filtration algorithms, e.g. MIDAS and PAC, for the detection of alternative splicing events. We include a biological filtration function according to GO terms, and provide a module to visualize and interpret the selected exons and transcripts. Furthermore, easyExon can integrate with other related programs, such as Integrate Genome Browser (IGB) and Affymetrix Power Tools (APT), to make the whole analysis more comprehensive. We applied easyExon on a public accessible colon cancer dataset as an example to illustrate the analysis pipeline of this tool. Conclusion EasyExon can efficiently process and analyze the Affymetrix exon array data. The simplicity, flexibility and brevity of easyExon make it a valuable tool for AS event identification in genomic research.

Abstract Background The identification of specific gene expression signature for distinguishing sample groups is a dominant field in cancer research. Although a number of tools have been developed to identify optimal gene expression signatures, the number of signature genes obtained is often overly large to be applied clinically. Furthermore, experimental verification is sometimes limited by the availability of wet-lab materials such as antibodies and reagents. A tool to evaluate the discrimination power of candidate genes is therefore in high demand by clinical researchers. Results Signature Evaluation Tool (SET) is a Java-based tool adopting the Golub's weighted voting algorithm as well as incorporating the visual presentation of prediction strength for each array sample. SET provides a flexible and easy-to-follow platform to evaluate the discrimination power of a gene signature. Here, we demonstrated the application of SET for several purposes: (1) for signatures consisting of a large number of genes, SET offers the ability to rapidly narrow down the number of genes; (2) for a given signature (from third party analyses or user-defined), SET can re-evaluate and re-adjust its discrimination power by selecting/de-selecting genes repeatedly; (3) for multiple microarray datasets, SET can evaluate the classification capability of a signature among datasets; and (4) by providing a module to visualize the prediction strength for each sample, SET allows users to re-evaluate the discrimination power on mis-grouped or less-certain samples. Information obtained from the above applications could be useful in prognostic analyses or clinical management decisions. Conclusion Here we present SET to evaluate and visualize the sample-discrimination ability of a given gene expression signature. This tool provides a filtration function for signature identification and lies between clinical analyses and class prediction (or feature selection) tools. The simplicity, flexibility and brevity of SET could make it an invaluable tool for marker identification in clinical research.

Infertility is one of the important problems in the modern world. Male infertility is characterized by several clinical manifestations, including low sperm production (oligozoospermia), reduced sperm motility (asthenozoospermia), and abnormal sperm morphology (teratozoospermia). WDR4, known as Wuho, controls fertility in Drosophila. However, it is unclear whether WDR4 is associated with clinical manifestations of male fertility in human. Here, we attempted to determine the physiological functions of WDR4 gene. Two cohorts were applied to address this question. The first cohort was the general population from Taiwan Biobank. Genomic profiles from 68,948 individuals and 87 common physiological traits were applied for phenome-wide association studies (PheWAS). The second cohort comprised patients with male infertility from Wan Fang Hospital, Taipei Medical University. In total, 81 male participants were recruited for the genetic association study. Clinical records including gender, age, total testosterone, follicle-stimulating hormone (FSH), luteinizing hormone (LH), total sperm number, sperm motility, and sperm morphology were collected. In the first cohort, results from PheWAS exhibited no associations between WDR4 genetic variants and 87 common physiological traits. In the second cohort, a total of four tagging single-nucleotide polymorphisms (tSNPs) from WDR4 gene (rs2298666, rs465663, rs2248490, and rs3746939) were selected for genotyping. We found that SNP rs465663 solely associated with asthenozoospermia. Functional annotations through the GTEx portal revealed the correlation between TT or TC genotype and low expression of WDR4 . Furthermore, we used mouse embryonic fibroblasts cells from mwdr4 heterozygous (+/‒) mice for functional validation by western blotting. Indeed, low expression of WDR4 contributed to ROS-induced DNA fragmentation. In conclusion, our results suggest a critical role of WDR4 gene variant as well as protein expression in asthenozoospermia.

Background: The oncogenic Kirsten rat sarcoma viral oncogene homolog ( KRAS ) mutation was reported to be the signature genetic event in most cases of pancreatic ductal adenocarcinoma (PDAC). Hepassocin (HPS/FGL1) is involved in regulating lipid metabolism and the progression of several cancer types; however, the underlying mechanism of HPS/FGL1 in the KRAS mutant PDAC cells undergoing eicosapentaenoic acid (EPA) treatment remains unclear., Methods: We measured HPS/FGL1 protein expressions in a human pancreatic ductal epithelial (HPNE) normal pancreas cell line, a KRAS -wild-type PDAC cell line (BxPC-3), and KRAS -mutant PDAC cell lines (PANC-1, MIA PaCa-2, and SUIT-2) by Western blot methods. HEK293T cells were transiently transfected with corresponding KRAS -expressing plasmids to examine the level of HPS expression with KRAS activation. We knocked-down HPS/FGL1 using lentiviral vectors in SUIT-2 cells and measured the cell viability by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and clonogenicity assays. Furthermore, a lipidomic analysis was performed to profile changes in lipid metabolism after HPS/FGL1 knockdown., Results: We found that the HPS/FGL1 level was significantly upregulated in KRAS -mutated PDAC cells and was involved in KRAS /phosphorylated (p)-signal transduction and activator of transcription 3 (STAT3) signaling, and the knockdown of HPS/FGL1 in SUIT-2 cells decreased cell proliferation through increasing G 2 /M cell cycle arrest and cyclin B1 expression. In addition, the knockdown of HPS/FGL1 in SUIT-2 cells significantly increased omega-3 polyunsaturated fatty acids (PUFAs) and EPA production but not docosahexaenoic acid (DHA). Moreover, EPA treatment in SUIT-2 cells reduced the expression of de novo lipogenic protein, acetyl coenzyme A carboxylase (ACC)-1, and decreased p-STAT3 and HPS/FGL1 expressions, resulting in the suppression of cell viability., Conclusions: Results of this study indicate that HPS is highly expressed by KRAS -mutated PDAC cells, and HPS/FGL1 plays a crucial role in altering lipid metabolism and increasing cell growth in pancreatic cancer. EPA supplements could potentially inhibit or reduce ACC-1-involved lipogenesis and HPS/FGL1-mediated cell survival in KRAS -mutated pancreatic cancer cells.

A liquid crystal elastomer (LCE) film is successfully deposited with a terahertz metamaterial using thermal evaporation via a programmed electronic shutter and high-efficiency cooling system. The transmittance of the metamaterial at its resonance frequency is monotonically increased from 0.0036 to 1.0 as a pump beam bends the LCE film, so the metamaterial has a large switching contrast of 277 at the frequency. The monotonic increase in the resonance transmittance arises from the constant resonance frequency of the metamaterial at the transmittance modulation and depicts that the metamaterial-deposited LCE film can continuously tune the transmitted intensity of a terahertz beam. The metamaterial-deposited LCE film has potential in developing continuously tunable intensity modulators with large switching contrasts for the application of terahertz imaging and terahertz communication. Therefore, the thermal evaporation expands the application of metamaterials and improves their optical properties.

Bisphenol A (BPA), an endocrine-disrupting chemical, is capable of producing reproductive toxicity. BPA results in mitochondrial DNA (mtDNA) deletion and mitochondrial dysfunction; however, the effect of BPA on the mitochondria of ovarian granulosa cells is not clear. Further, 1,25-dihydroxyvitamin D 3 (1,25D 3 ) may play a role in reproduction, because its receptor, VDR, contributes to the inhibition of oxidative stress and predominantly exists in the nuclei of granulosa cells. Hence, the role of 1,25D 3 in BPA-mediated effects on mitochondrial function was examined in this study. Primary rat granulosa cells treated with BPA, 1,25D 3 , or both were subjected to molecular/biochemical assays to measure cell survival, mtDNA content, mtDNA deletion, superoxide dismutase activity, levels of proteins related to mitochondrial biogenesis, and mitochondrial function. We found that cell viability was dose-dependently reduced and reactive oxygen species (ROS) levels were increased by BPA treatment. BPA administration elevated Mn-superoxide dismutase (MnSOD) expression but negatively regulated total SOD activity. 1,25D 3 treatment alone increased 17β-estradiol secretion, ATP production, and cellular oxygen consumption. In cells treated with both agents, 1,25D 3 enhanced BPA-induced MnSOD protein upregulation and blocked the BPA-mediated decline in total SOD activity. Furthermore, 1,25D 3 attenuated BPA-mediated mtDNA deletion but showed no effect on BPA-induced increases in mtDNA content. Although BPA had no influence on the levels of peroxisome proliferator-activated receptor-γ coactivator-1 α, nuclear respiratory factor-1, mitochondrial transcription factor A, or cytochrome c oxidase subunit IV, 1,25D 3 plus BPA markedly increased mitochondrial biogenesis-related protein expression via the PI3K-Akt pathway. Moreover, BPA-mediated negative regulation of cytochrome c oxidase subunit I levels and 17β-estradiol secretion was attenuated by 1,25D 3 pre-treatment. Our results suggest that 1,25D 3 attenuates BPA-induced decreases in 17β-estradiol and that treatment with 1,25D 3 plus BPA regulates granulosa cell mitochondria by elevating mitochondrial biogenesis-related protein levels., (Copyright © 2018. Published by Elsevier Ltd.)

Objective: To evaluate the impact of the number of retrieved oocytes on pregnancy outcome., Materials and Methods: We retrospectively examined the cycles of 2491 women undergoing in vitro fertilization therapy at Taipei Medical University (Taipei, Taiwan) from August 1995 to March 2009. We divided them into three groups based on their response rate (where H = high, M = middle, and L = low). We conducted this study to evaluate and compare pregnancy outcome in these three groups., Results: The total number of retrieved oocytes had a significantly positive correlation with peak E2 levels, and the number of fertilized oocytes, good quality embryos, and available frozen embryos. The number of retrieved oocytes had a positive correlation with pregnancy rates and a negative correlation with fertilization rates. The implantation and abortion rates among the three groups were essentially the same. Compared to the middle and higher responders, the pregnancy rates for lower responders were significantly lower. The pregnancy rates for middle responders and higher responders were not significantly different., Conclusion: The benefits of more retrieved oocytes between the lower and the middle responders were obvious. However, the benefits and risks for retrieving more oocytes for the middle and the higher responders remained controversial., (Copyright © 2016. Published by Elsevier B.V.)

Aim: The aim of this study was to investigate the biomarkers of insulin resistance in non-obese women., Design: This was a retrospective study., Patients: A total 229 non-obese women (Body mass index: BMI < 25) were evaluated., Main Outcome Measure(s): Serum levels of various androgens, cardiovascular risk and metabolic components., Results: There were no significant differences in the prevalence of polycystic ovary syndrome (PCOS), hyperprolactinemia, or premature ovarian failure (POF) between the non-obese women with and without insulin resistance. Non-obese women with insulin had significantly higher serum thyroid stimulation hormone (TSH) levels and resistin and lower serum adiponectin levels than non-obese women without insulin resistance; however, the inflammatory biomarkers and serum androgen levels did not differ between the two groups. Furthermore, using step-wise multivariate regression analysis applied by the risk factors listed above, TSH was the only predictive factor for insulin resistance in non-obese reproductive-aged women., Conclusions: Thyroid function should play an important role in developing insulin resistance for non-obese women. Serum androgens and inflammation might not contribute to insulin resistance in these women.

Objective: To evaluate the roles of obesity and inflammatory biomarkers associated with medical complications in women with PCOS., Study Design: Retrospective, BMI-matched study. A total of 330 patients, including 165 women with PCOS and 165 women without PCOS, were evaluated. The insulin resistance (homeostasis model assessment insulin resistance index - HOMA) and lipid profiles were assessed. The adiponectin, leptin, ghrelin, resistin, anti-müllerian hormone (AMH), sex hormone-binding globulin (SHBG), high sensitivity C-reactive protein (hs-CRP), and interleukin-6 (IL-6) levels were also measured., Results: Women with PCOS had significantly higher AMH, fasting insulin, total cholesterol, and low-density lipoprotein levels and lower SHBG levels compared with the controls. There was no difference in the serum obesity and inflammatory biomarkers between the PCOS cases and the controls. After adjusting for BMI and age, IL-6 was positively correlated with HOMA, and SHBG was negatively correlated with HOMA, triglyceride, and LDL., Conclusions: The serum adipokines levels are not good markers for PCOS. PCOS patients were characterized by their high AMH and low SHBG levels. A low level of SHBG should play an important role in the pathogenesis of the medical complications observed in women with PCOS. Clinical trial registration number NCT01989039., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Polycystic ovary syndrome (PCOS) is one of the most common hormonal endocrine disorders in women of reproductive age. It consists of a heterogeneous collection of signs and symptoms that together form a disorder spectrum. The diagnosis of PCOS is principally based on clinical and physical findings. The extent of metabolic abnormalities in women with PCOS varies with phenotype, body weight, age, and ethnicity. For general population, the prevalence of hyperandrogenism and oligomenorrhea decreases with age, while complications such as insulin resistance and other metabolic disturbances increase with age. Obese women with PCOS have a higher risk of developing oligomenorrhea, amenorrhea, hyperandrogenemia, insulin resistance, and lower luteinizing hormone (LH) to follicle stimulation hormone (FSH) ratios than non-obese women with PCOS. The LH to FSH ratio is a valuable diagnostic tool in evaluating Taiwanese women with PCOS, especially in the diagnosis of oligomenorrhea. Overweight/obesity is the major determinant of cardiovascular and metabolic disturbances in women of reproductive age.

Objective: The aim of this study is to evaluate serum ferritin levels and polycystic ovary syndrome (PCOS)-related complications in obese and nonobese women., Materials and Methods: This retrospective study included 539 (286 with PCOS and 253 without PCOS)., Results: Serum ferritin correlated with menstrual cycle length, sex hormone-binding globulin, total testosterone, androstenedione, triglyceride, and total cholesterol in both obese and nonobese women. Obese women with high ferritin levels exhibited higher insulin resistance, impaired glucose tolerance, and liver enzymes (glutamic oxaloacetic transaminase, glutamic pyruvic transaminase) than obese women with low ferritin levels. However, among nonobese women, insulin resistance and risk of diabetes were not significantly different between the high and low ferritin groups. Independent of obesity, hypertriglyceridemia was the major metabolic disturbance observed in women with elevated serum ferritin levels., Conclusion: Elevated serum ferritin levels are associated with increased insulin resistance and risk of diabetes in obese women but not in nonobese women. However, higher serum ferritin levels were correlated with a greater risk of hyperglyceridemia in both obese and nonobese women. Therefore, hypertriglyceridemia in women with PCOS might be associated with iron metabolism., (Copyright © 2015. Published by Elsevier B.V.)

Aim: The objective of this study was to evaluate the adiponectin and leptin levels in overweight/obese and lean women with polycystic ovary syndrome (PCOS)., Design: This was a retrospective study., Patients: Of the 422 studied patients, 224 women with PCOS and 198 women without PCOS were evaluated., Main Outcome Measure(s): Insulin resistance and the metabolic components were assessed. The adiponectin and leptin levels were also evaluated., Results: Adiponectin was negatively correlated with insulin resistance, body mass index (BMI), and total testosterone, triglyceride, and low-density lipoprotein (LDL) levels; conversely, leptin reversed the aforementioned reaction and was negatively correlated with adiponectin levels. The adiponectin to leptin ratios were significantly lower in PCOS women than in those without PCOS. Compared to women with non-PCOS, overweight/obese women with PCOS had lower serum adiponectin levels than women without PCOS, which was not the case for lean women. Conversely, lean women with PCOS had higher serum leptin levels than those without PCOS, which was not the case for overweight/obese women., Conclusions: Adipose tissue might play an important role in the metabolic complications in women with PCOS. To study the impact of obesity biomarkers in women with PCOS, overweight/obese and lean women should be considered separately.

Anti-Müllerian hormone (AMH) level has been found to be a useful marker of ovarian reserve, and a predictor of poor and hyper-responses in patients undergoing controlled ovarian stimulation (COS). The study aimed to determine the association of serum AMH level with achieving pregnancy in patients undergoing COS with intrauterine insemination. The cross-sectional study investigated 204 patients who underwent COS with intrauterine insemination at the Obstetrics and Gynecology Department of Taipei Medical University Hospital, from January 2011 to March 2012. The medical records of these patients were reviewed, and serum AMH levels were evaluated for association with successful clinical pregnancy. The AMH level in the patients who achieved clinical pregnancy was significantly higher than in patients who did not (median 2.7 vs 2.0 ng/ml, p = 0.005). Controlling for factors affecting infertility, AMH level had a significant independent influence on outcome; a higher AMH level was associated with a decreased risk of a non-pregnant outcome (odds ratio, OR = 0.895, p = 0.026). In patients undergoing COS and intrauterine insemination, a low AMH level is associated with a decreased chance of a clinical pregnancy, and this association remains irrespective of the presence or absence of endometriosis.

Chemotherapy damages the reproductive system by enhancing apoptosis, and evidence suggests that targeted anti-apoptotic therapy may preserve fertility in patients receiving chemotherapy. To investigate the protective effect of sphingosine-1-phosphate (S1P) on chemotherapeutic agent-induced ovarian gonadotoxicity, busulfan-treated female mice were pre-treated with low (0.5 mM) and high (2.0 mM) doses of S1P or vehicle 1 h before busulfan injection. In the S1P groups, each mouse was injected with low-dose S1P in one ovary and high-dose S1P in the contralateral ovary. Four weeks later, the ovaries were removed for histological and biochemical examinations. Caspase 3 immunoreactivity was greater in mice treated with busulfan compared with mice pre-treated with S1P, in which more primordial follicles were observed (P < 0.05). The mRNA level of anti-Müllerian hormone was higher in mice pre-treated with S1P than those that received busulfan only, indicating a better ovarian function in mice pre-treated with S1P. No difference was observed in the levels of growth differentiation factor-9 among all groups. In conclusion, S1P protects primordial follicles from chemotherapy-induced gonadotoxicity, and may partially preserve ovarian function., (Copyright © 2014 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

Background: Aromatase converts testosterone into 17beta-estradiol in granulosa cells, and the converted 17beta-estradiol contributes to follicular maturation. Additionally, excessive testosterone inhibits aromatase activity, which can lead to concerns regarding polycystic ovary syndrome (PCOS). Generally, 1,25-dihydroxyvitamin D3 (1,25D3) supplements help to improve the symptoms of PCOS patients who exhibit low blood levels of 1,25D3. Therefore, this study investigated the interaction effects of 1,25D3 and testosterone on estrogenesis and intercellular connections in rat granulosa cells., Methods: Primary cultures of granulosa cells were treated with testosterone or testosterone plus 1,25D3, or pre-treated with a calcium channel blocker or calcium chelator. Cell lysates were subjected to western blot analysis to determine protein and phosphorylation levels, and 17beta-estradiol secretion was examined using a radioimmunoassay technique. Cell viability was evaluated by MTT reduction assay. Connexin 43 (Cx43) mRNA and protein expression levels were assessed by qRT-PCR, western blot, and immunocytochemistry., Results: Testosterone treatment (0.1 and 1 microg/mL) increased aromatase expression and 17beta-estradiol secretion, and the addition of 1,25D3 attenuated testosterone (1 microg/mL)-induced aromatase expression but improved testosterone-induced 17beta-estradiol secretion. Furthermore, testosterone-induced aromatase phosphotyrosine levels increased at 10 min, 30 min and 1 h, whereas 1,25D3 increased the longevity of the testosterone effect to 6 h and 24 h. Within 18-24 h of treatment, 1,25D3 markedly enhanced testosterone-induced 17beta-estradiol secretion. Additionally, pre-treatment with a calcium channel blocker nifedipine or an intracellular calcium chelator BAPTA-AM reduced 1,25D3 and testosterone-induced 17beta-estradiol secretion. Groups that underwent testosterone treatment exhibited significantly increased estradiol receptor beta expression levels, which were not affected by 1,25D3. Neither testosterone nor 1,25D3 altered 1,25D3 receptor expression. Finally, at high doses of testosterone, Cx43 protein expression was decreased in granulosa cells, and this effect was reversed by co-treatment with 1,25D3., Conclusions: These data suggest that 1,25D3 potentially increases testosterone-induced 17beta-estradiol secretion by regulating aromatase phosphotyrosine levels, and calcium increase is involved in both 1,25D3 and testosterone-induced 17beta-estradiol secretion. 1,25D3 reverses the inhibitory effect of testosterone on Cx43 expression in granulosa cells.

Objective: Menstrual irregularity is one of the major complaints in women of reproductive age. The aim of this study was to evaluate the complications in women with different menstrual disturbances., Materials and Methods: This is a retrospective study. A total of 576 women were screened first, and 470 women were included later [257 women with oligo/amenorrhea (149 hyperandrogenic and 108 nonhyperandrogenic women) and 213 normocyclic controls]. Endocrine and metabolic parameters and insulin resistance were compared among different menstrual patterns., Results: The average duration of menstrual cycle length was positively correlated with age, levels of androgens and prolactin, lipid profiles, and the parameters of insulin resistance. Hyperandrogenic women with amenorrhea had higher levels of androgens and more lipid profiles disorders than hyperandrogenic women with oligomenorrhea. However, nonhyperandrogenic women with amenorrhea had a degree of insulin resistance and metabolic disturbance similar to that of nonhyperandrogenic women with oligomenorrhea. Interestingly, for women with normal prolactin levels, serum prolactin levels were significantly lower in amenorrhea than oligomenorrhea in both hyperandrogenic and nonhyperandrogenic groups., Conclusion: The degree of menstrual disturbances does not correlate with the severity of insulin resistance and metabolic disturbances in women without excess levels of androgen. For women with normal prolactin levels, amenorrheic patients had significantly lower serum prolactin levels than oligomenorrheic patients., (Copyright © 2014. Published by Elsevier B.V.)

Objective: To study the association between endocrine disturbances and metabolic complications in women seeking gynecologic care., Design: Retrospective study, cluster analysis., Setting: Outpatient clinic, university medical center., Patient(s): 573 women, including 384 at low risk and 189 at high risk of cardiometabolic disease., Intervention(s): None., Main Outcome Measure(s): Cardiovascular and metabolic parameters and clinical and biochemical characteristics., Result(s): Risk factors for metabolic disease are associated with a low age of menarche, high levels of high-sensitivity C-reactive protein and liver enzymes, and low levels of sex hormone-binding globulin. Overweight/obese status, polycystic ovary syndrome, oligo/amenorrhea, and hyperandrogenism were found to increase the risk of cardiometabolic disease. However, hyperprolactinemia and premature ovarian failure were not associated with the risk of cardiometabolic disease. In terms of androgens, the serum total testosterone level and free androgen index but not androstenedione or dehydroepiandrosterone sulfate (DHEAS) were associated with cardiometabolic risk., Conclusion(s): Although polycystic ovary syndrome is associated with metabolic risk, obesity was the major determinant of cardiometabolic disturbances in reproductive-aged women. Hyperprolactinemia and premature ovarian failure were not associated with the risk of cardiovascular and metabolic diseases., Clinical Trial Registration Number: NCT01826357., (Copyright © 2014 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Background: The International Classification of Functioning, Disability, and Health (ICF) provides a framework for measuring functioning and disability based on a biopsychosocial model., Aim: The aim of this study was to develop comprehensive and brief ICF core sets for morbid obesity for disability assessment in Taiwan., Design: Observational, Setting: Other, Population: Twenty-nine multidisciplinary experts of ICF METHODS: The questionnaire contained 112 obesity-relevant and second-level ICF categories. Using a 5-point Likert scale, the participants rated the significance of the effects of each category on the heath status of people with obesity. Correlation between an individual's score and the average score of the group indicated consensus. The categories were selected for the comprehensive core set for obesity if more than 50% of the experts rated them as "important" in the third round of the Delphi exercise, and for the brief core set if more than 80% of the experts rated them "very important.", Results: Twenty-nine experts participated in the study. These included 18 physicians, 4 dieticians, 3 physical therapists, 2 nurses, and 2 ICF experts. The comprehensive core set for morbid obesity contained 61 categories. Of these, 26 categories were from the component body function, 8 were from body structure, 18 were from activities and participation, and 9 were from environmental factors. The brief core set for obesity disability contained 29 categories. Of these, 19 categories were from the component body function, 3 were from body structure, 6 were from activities and participation, and one was from environmental factors. The comprehensive and brief ICF core sets provide comprehensive information on the health effects of morbid obesity and concise information for clinical practice., Conclusion: Comprehensive and brief core sets were created after three rounds of Delphi technique. Further validation study of these core sets by applying to patients with morbid obesity is needed., Clinical Rehabilitaiton Impact: The comprehensive ICF core set for morbid obesity provides comprehensive information on the health effects of morbid obesity; the brief core set can provide concise information for clinical practice.

Significant follicle loss from frozen ovarian grafts is unavoidable. The authors evaluated the protective effects of the antiapoptotic agent sphingosine-1-phosphate (S1P) on vitrified ovarian grafts. Three-week-old sexually immature female FVB mice were divided into 4 groups, fresh, control without S1P, 0.5 mmol/L S1P, and 2 mmol/L S1P. The ovaries were pretreated with S1P for 1 hour and then cryopreserved by modified vitrification. The frozen-thawed ovaries were autotransplanted under the back muscles of mice for 10 days. Expression of apoptosis-related genes encoding caspase 3 and c-Myc was analyzed in the vitrified ovaries and 10 days after transplantation using real-time quantitative polymerase chain reaction. To quantify the ovarian reserve, anti-Müllerian hormone (AMH) levels and follicles were measured in the 10-day vitrified ovarian grafts. Caspase 3 and c-Myc messenger RNA did not differ significantly in the 4 groups after vitrification but was significantly upregulated in the control group after transplantation. The AMH levels and primordial follicle pool were significantly higher in the S1P-treated groups than in the control group but lower than that in the fresh group. The S1P protects vitrified ovarian grafts from ischemic reperfusion injury rather than from vitrification-associated process.

Objective: Inflammation is an important risk factor for the development of colorectal cancer (CRC). Pelvic inflammatory disease (PID) comprises a spectrum of upper genital tract infections and inflammatory diseases. We aimed to evaluate the association between CRC and PID., Design: Matched cohort study using the National Health Insurance Research Database., Setting: Women with PID in Taiwan., Population and Sample: From the Longitudinal Health Insurance Database 2005 (LHID2005) in Taiwan, we obtained data on women from 13 to 45 years of age who were diagnosed with PID. The women with PID were matched 1:4 to selected members of the population without PID based on age and year of first entry into the LHID2005., Methods: A Cox proportional hazards model was used to evaluate the hazard ratio for CRC during the 5-year follow-up period, after adjusting for sociodemographic characteristics and selected comorbid medical disorders., Main Outcome Measures: Colorectal cancer., Results: Of the 19,029 women with PID, 30 were diagnosed with CRC during the 78,965 person-year follow-up period. Of the 76,116 control women, 66 were diagnosed with CRC. The CRC hazard ratio during the 5-year follow-up period was 2.00 (95% CI 1.30-3.08) for women with PID relative to control women. Similarly, after adjusting for age, Charlson comorbidity index score, urbanisation level and monthly income, the adjusted CRC hazard ratio was 1.71 (95% CI 1.10-2.65) for the women with PID relative to the women in the comparison cohort., Conclusions: Here we show a weak association between PID and CRC. Additional studies are needed to further evaluate this association and examine plausible mechanisms, including the influence of specific microorganisms., (© 2013 Royal College of Obstetricians and Gynaecologists.)

Objective: Hyperhomocysteinaemia is a well-established risk factor for cardiovascular disease. This study investigated the relationship between hyperhomocysteinaemia and factors related to polycystic ovary syndrome (PCOS)., Study Design: Case-control study. Three hundred and thirty-nine women were included; of these, 84 had hyperhomocysteinaemia (homocysteine>12.4 μmol/l) and 255 had normal homocysteine levels. Homocysteine, high-sensitivity C-reactive protein, insulin resistance, metabolic disturbance and PCOS-related disturbance were evaluated. The clinical and biochemical characteristics of women with hyperhomocysteinaemia and normal homocysteine levels, including insulin resistance, metabolic disturbance and PCOS-related disturbance, were compared., Results: Correlation was found between serum homocysteine level and serum total testosterone level and diastolic blood pressure. No correlation was found between serum homocysteine level and age, body mass index, insulin resistance and lipid profile. Women with hyperhomocysteinaemia had a significantly higher risk for biochemical hyperandrogenaemia and higher serum total testosterone levels than women with normal homocysteine levels. The prevalence rates of PCOS, oligo-amenorrhoea, polycystic ovary morphology and metabolic disturbance did not differ between the two groups. The parameters of insulin resistance and lipid profiles were similar between the two groups, and signs of clinical hyperandrogenism (hirsutism and the modified Ferriman-Gallwey score) did not differ between the two groups. Logistic regression analysis found a significant association between hyperandrogenaemia and hyperhomocysteinaemia (odds ratio 2.24, 95% confidence interval 1.26-4.01)., Conclusions: For women with PCOS, an elevated serum total testosterone level is the main factor associated with hyperhomocysteinaemia. The association between biochemical hyperandrogenism and hyperhomocysteinaemia may contribute to cardiovascular risk for women with PCOS., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

Background: Hypertension induces cardiac dysfunction, calcium (Ca(2+)) dysregulation, and arrhythmogenesis. Dipeptidyl peptidase (DPP)-4 inhibitors, an antidiabetic agent with anti-inflammation and anti-hypertension potential, may regulate peroxisome proliferator-activated receptors (PPARs)-α, -γ, and -δ and Ca(2+) homeostasis., Objective: The purpose of this study was to investigate whether DPP-4 inhibitor, sitagliptin, can modulate PPARs and Ca(2+) handling proteins in hypertensive hearts., Methods: A Western blot analysis was used to evaluate protein expressions of myocardial PPAR isoforms, tumor necrosis factor (TNF)-α, interleukin (IL)-6, sarcoplasmic reticulum ATPase (SERCA2a), Na(+)-Ca(2+) exchanger (NCX), ryanodine receptor (RyR), voltage-dependent Ca(2+) (CaV1.2), slow-voltage potassium currents (Kvs), angiotensin II type 1 receptor (AT1R), and receptor of advanced glycated end-products (RAGE) from Wistar-Kyoto (WKY) rats, spontaneously hypertensive rats (SHR), and SHR treated with sitagliptin (10mg/kg for 4weeks). Conventional microelectrodes were used to record action potentials (APs) in the ventricular myocytes from each group., Results: Compared to the control group, SHR had lower cardiac PPAR-α and PPAR-δ protein expressions, but had greater cardiac PPAR-γ levels, and TNF-α, IL-6, RAGE, and AT1R protein expressions, which were ameliorated in the sitagliptin-treated SHR. SHR had prolonged QT interval and AP duration with less SERCA2a and RyR, and greater CaV1.2 expressions, which were also attenuated in sitagliptin-treated SHR., Conclusions: Sitagliptin significantly changed the cardiac electrophysiological characteristics and Ca(2+) regulation, which may have been caused by its effects on cardiac PPARs, proinflammatory cytokines, and AT1R., (© 2013.)

Polycystic ovarian syndrome (PCOS) is the most common endocrine disorder of reproductive-age women. The diagnosis of PCOS is mainly based on the following three components: (1) hyperandrogenism, (2) oligo-amenorrhea, and (3) the observation of polycystic ovaries on a sonogram. The comorbidities may include insulin resistance, type II diabetes mellitus, hypertension and cardiovascular disease. Importantly, the diagnostic criteria and complications related to PCOS are age-dependent. Androgen production in women may decrease because of ovarian aging or decreased production by the adrenal glands over time. The prevalence of hirsutism and acne decreases with age. Ovarian volume and follicle number also decrease with age, with the age-related decrease in follicle number seemingly greater than that of ovarian volume. Aging may also be associated with increased risk of insulin resistance and metabolic disturbances. Therefore, these age-related changes may affect the observed incidence and complications of PCOS. In adolescent patients, the criteria described above pose particular diagnostic problems because the characteristics of normal puberty often overlap with the signs and symptoms of PCOS. Hyperandrogenism and chronic anovulation are the primary disturbances in younger women with PCOS; whereas, obesity, insulin resistance, and metabolic disturbances are predominant in older women with PCOS. The deterioration of insulin resistance during the reproductive life of women with PCOS appears to be mainly attributable to the increase in obesity. Therefore, if body weight could be controlled properly, younger hyperandrogenic PCOS women might reduce their risk of insulin resistance and metabolic disturbances later in life., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Background: There is evidence that chronic inflammation may promote atherosclerotic disease. The purpose of this study was to test the hypothesis that pelvic inflammatory disease (PID) is a risk marker for myocardial infarction (MI)., Method: Using the Taiwan Longitudinal Health Insurance Database 2005 (LHID2005), this cohort study comprised patients with a recorded diagnosis of PID (N=68,668) between January 1, 2004 and December 31, 2005, with age-matched controls (1:2) (N=136,906). Each patient was followed-up using entry data until the end of 2006. Cox proportional hazard regressions were used to evaluate the up to 3-year MI-free survival rates, after adjusting for known confounding factors., Results: We found that patients with PID were more likely to have MI than the control population after adjusting for potential confounders [adjusted hazard ratio (HR), 1.86, 95% confidence interval (CI), 1.23-2.81]. When stratified by patient's age, the adjusted HR for MI was 2.09 (95% CI, 1.24-3.52) for patients with PID aged over 55 years. However, the adjusted HR for MI occurring was not significant for patients with PID aged ≤ 55 years., Conclusions: PID is a risk marker for MI that is independent of traditional MI risk factors. Further research in this important area of public health is warranted., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

This study is designed to evaluate the relationship between endometrial thickness and clinical/biochemical parameters in women with chronic anovulation. One hundred and twenty women with ovulatory dysfunction were prospective included, endometrial thickness and endocrine and metabolic parameters were measured. The interval between the examination day and the day of the most recent menstrual bleeding (the anovulatory interval) for the studied subject was an average of 145 ± 186 days. The endometrial thickness averaged 7.1 ± 3.2 mm. Correlation analyses revealed that the endometrial thickness was positively correlated with body mass index but was not correlated with age, serum androgens, or estradiol (E2) levels. We further classified the subjects into two groups based on endometrial thickness: Group A, endometrial thickness <7 mm and Group B, endometrial thickness ≥7 mm. The anovulatory interval, follicle-stimulating hormone, luteinizing hormone, E2 and androgen levels were not significantly different between Groups A and B. Group B had higher body weight and more risk for metabolic syndrome. We concluded that endometrial thickness in women with ovulatory dysfunction is positively correlated with body weight status but is not correlated with serum androgens or E2 levels.

Background: Androgen is a steroid hormone associated with high blood pressure (BP). The effect of androgen on BP in females is unknown., Methods: Androgen, vascular endothelial growth factor (VEGF), interleukin (IL)-6 and matrix metalloproteinase (MMP)-9 were evaluated in females with menstruation disorders (n = 135, 28 ± 5 years old) and normal BP, pre-hypertension, stage 1 hypertension, and stage 2 hypertension., Results: Normal-BP (n = 57), pre-hypertension (n = 44), stage-1-hypertension (n = 21), and stage-2-hypertension (n = 13) females had similar androgen (3.3 ± 1.5, 2.7 ± 1.2, 3.1 ± 1.4, and 3.5 ± 1.3 ng/ml, p > 0.05) and IL-6 levels (1.7 ± 2.2, 1.9 ± 2.6, 1.3 ± 1.2 and 2.4 ± 3.3 pg/ml, p > 0.05). However, normal BP females had lower MMP-9 (609 ± 307 versus 891 ± 385 ng/ml, p < 0.05) than stage-1-hypertension females. In addition, normal BP females had lower VEGF (166 ± 103 versus 255 ± 139, 272 ± 128 and 301 ± 216 pg/ml, p < 0.05) than the other three groups. In normal-androgen females, VEGF levels were similar among the four groups. However, in high-androgen females, normal BP groups had lower VEGF levels than pre-hypertension, stage-1, and stage-2 hypertension groups (166 ± 94 versus 294 ± 153, 281 ± 160 and 357 ± 253 p < 0.05)., Conclusions: Androgen can modulate growth factors and extracellular matrix proteins, which may contribute to the pathophysiology of hypertension in young females.

Polycystic ovary syndrome (PCOS) is a common and complex female endocrinopathy that is associated with multiple vascular risk factors. Our objective was to investigate the relationship between carotid intima-media thickness (CIMT) and endogenous androgens in young Taiwanese-Chinese women with PCOS. We measured CIMT with B-mode ultrasound in 42 young PCOS patients and 43 controls. Atherosclerosis-associated profiles and endocrinological parameters were also measured. The results showed that although Taiwanese-Chinese PCOS patients tend to possess more risk factors for atherosclerosis than controls, there was no evidence to support that they have a greater CIMT at this age. Furthermore, androstenedione appears to be inversely associated with CIMT.

Polycystic ovary syndrome (PCOS), the most common endocrine disorder affecting women of reproductive age, is characterized by hyperandrogenism and insulin resistance. Women with PCOS have a higher risk for cardiovascular diseases (CVDs) and endothelial dysfunction. The mechanisms underlying these risks are unclear. Human peripheral blood contains circulating endothelial progenitor cells (EPCs) derived from bone marrow that have the ability to proliferate and differentiate into mature endothelial cells, which may contribute to vessel homeostasis and repair. PCOS is associated with insulin resistance, hyperinsulinemia, and dyslipidemia, which may result in EPC dysfunction. In this review, we summarize the potential mechanisms of EPC dysfunction in PCOS, which possibly result in a higher genesis of CVDs in PCOS-affected subjects.

Objective: To evaluate the contribution to glucose intolerance and metabolic syndrome of obesity combined with the diagnostic criteria of polycystic ovary syndrome (PCOS)., Design: Prospective study., Setting: University teaching hospital from 31 August 2010 to 31 August 2011., Population: Two hundred and twenty women with PCOS and seventy normal control women., Methods: The clinical and biochemical characteristics of women with PCOS and control women were evaluated. Main outcome measures. The impact of obesity, hyperandrogenism, oligo-anovulation and polycystic ovary morphology on impaired glucose tolerance and metabolic disturbances., Results: Obese women with PCOS had significantly higher insulin resistance than obese normal control women. Logistic regression analysis showed that obesity was the only factor that predicted impaired glucose tolerance and metabolic syndrome. Use of the area under the receiver operating characteristic curve (AUROC) for the body mass index to predict impaired glucose tolerance and metabolic syndrome was more accurate than AUROCs for serum total testosterone level and the average menstrual interval., Conclusions: Body weight status was the major factor determining the risk of impaired glucose tolerance and metabolic syndrome in women with PCOS. Obesity should be treated as the major factor determining long-term health consequences associated with PCOS., (© 2012 The Authors Acta Obstetricia et Gynecologica Scandinavica© 2012 Nordic Federation of Societies of Obstetrics and Gynecology.)

Study Objective: To describe the changing trend, repeat operation rate, and distribution of laparoscopy, as compared with laparotomy, in treating ectopic pregnancy, according to patient age, preoperative conditions, surgeon age, and hospital accreditation level, in Taiwan over 11-years., Design: Retrospective cohort study (Canadian Task Force classification II-2)., Setting: Population-based nationwide insurance database., Patients: Women who underwent either laparotomy or laparoscopy because of ectopic pregnancy., Interventions: Women who had National Health Insurance (NHI) underwent various surgical procedures to treat ectopic pregnancy. Data for this study were obtained from the Inpatient Expenditures by Admissions files of the NHI Research Database, released by the NHI program in Taiwan between 1997 and 2007., Measurements and Main Results: A total of 43 170 women with 44 928 operations were identified. Only the primary surgeries, via either laparotomy or laparoscopy, performed because of ectopic pregnancy were included for analysis. The annual number of procedures to treat ectopic pregnancies decreased in the later years of the 11-year study. Laparotomy decreased significantly, from 81.2% in 1997 to 26.2% in 2007, whereas laparoscopic procedures increased significantly, from 18.8% in 1997 to 73.8% in 2007, as evidenced at log-linear regression analysis (p < .001). The rate of repeat operations because of persistent ectopic pregnancy was higher in the laparoscopy group than in the laparotomy group (0.38% vs 0.14 %; p < .001). Patients were more likely to undergo the same type of operation for the repeated surgery (i.e., laparotomy to laparotomy in 73.1% or laparoscopy to laparoscopy in 80.2%; p = 0.43). Use of laparoscopy (58.1%) and laparotomy (41.9%) differed according to patient age, preoperative comorbidities, surgeon age, and hospital accreditation level and ownership type. With older patients, those with preoperative anemia or shock, and elder surgeons, there was a greater chance that laparotomy would be performed. The probability of undergoing laparotomy was greater in patients in regional hospitals, local hospitals, and office-based clinics compared with those in medical centers., Conclusions: There has been considerable change in the type of surgical approach used to treat ectopic pregnancy in Taiwan over the past 11 years. Laparoscopy is preferred to laparotomy, and has become the standard surgical approach to treating ectopic pregnancies in Taiwan. However, laparoscopy is associated with a higher rate of repeat operations. The laparoscopic approach signifies a profound change in treating ectopic pregnancies among patients, surgeons, and hospital types., (Copyright © 2012 AAGL. Published by Elsevier Inc. All rights reserved.)

The purpose of this prospective study was to evaluate Kruger strict morphology and conventional semen analysis in predicting cryosurvival and the progressive motility recovery rate of frozen spermatozoa. Our study included 56 semen samples with >10 million spermatozoa per ejaculate. The main outcome measures were conventional semen analysis, strict morphology analysis by the Kruger method, cryosurvival rate and post-thaw sperm motility. A significant reduction in sperm motility after cryopreservation was demonstrated. The freeze-thawing process caused a 66% reduction in rapid progressive motile spermatozoa, a 45% reduction in slow progressive motile spermatozoa and a 2% reduction in nonprogressive motile spermatozoa. The cryosurvival and progressive motility recovery rates were not correlated with parameters of conventional semen analysis, such as sperm concentration, motility, WHO morphology and total motile count, but the progressive motility recovery rate was significantly correlated with the percentage of spermatozoa exhibiting Kruger normal morphology (P = 0.028). The recovery rate of rapidly progressive motility was profoundly decreased compared with slow progressive motility following the frozen-thaw procedure of semen. Kruger strict morphology assessment was a better predictor of the progressive motility recovery rate following the freezing-thaw procedure than parameters of conventional semen analysis., (© 2011 Blackwell Verlag GmbH.)

Background: The clinical features and metabolic complications of polycystic ovary syndrome (PCOS) may change with age. This study was designed to investigate the clinical and biochemical characteristics of PCOS patients between the ages of 20 and 40., Methods: The study included 781 Taiwanese women, of whom 453 were diagnosed with PCOS and 328 were non-PCOS controls. Anthropometric components, androgens, endocrine, insulin resistance, and metabolic components were measured and correlated with age. Above parameters were compared between younger and elder women with PCOS., Results: Age had significant negative correlations with androgens (total testosterone and dehydroepiandrosterone sulfate), the modified Ferriman-Gallwey score and the prevalence of acne and hirsutism. Age had significant positive correlations with fasting glucose, cholesterol, triglycerides and low-density lipoprotein. The 453 women who fulfilled diagnostic criteria for PCOS were classified by age into two groups: Group A (20-29 years old, n= 294) and Group B (30-40 years old, n= 159). Group A had significantly higher total testosterone levels than Group B. Group B had higher fasting insulin and glucose levels, triglycerides, body mass index and waist measurements and a higher incidence of obesity than Group A. The average ovarian volume was not significantly different among the two groups., Conclusions: Increased age is accompanied by a decrease in the prevalence of both clinical and biochemical hyperandrogenism in women. Hyperandrogenism is the important factor for young women with PCOS; however, abdominal obesity and certain metabolic disturbances became major concerns for older women with PCOS.

Objective: Sonographic gray-scale histogram is used to assess the endometrial changes in the different phases of the menstrual cycle. The objective was to examine the usefulness of a gray-scale histogram and computer-assisted image analysis software in assessing normal physiologic states of the endometrium with sonography., Materials and Methods: Thirty-eight patients, who visited the Taipei Medical University-Wan Fang Hospital and matched the eligibility criteria, were categorized into one of three groups: (1) menstrual phase; (2) follicular phase; and (3) luteal phase of the menstrual cycle. Ultrasonography of the uterus was performed on each patient and the endometrium was analyzed with ImageJ image analysis software., Results: A statistically significant difference in signal intensity scores of the gray-level histogram, represented as m(j), was found among the three groups., Conclusion: Sonographic images analyzed by using computer-assisted image analysis software and gray-level histogram are proven to be useful in assessing the physiological state of the endometrium., (Copyright © 2011. Published by Elsevier B.V.)