Genome-wide analysis of cervical secretions obtained during embryo transfer reveals the association between deoxyribonucleic acid methylation and pregnancy outcomes.

OBJECTIVE: To study whether the methylation status of cervical secretions can reflect the ability of the endometrium to allow embryo implantation. DESIGN: Case-control study. SETTING: In vitro fertilization centers. PATIENT(S): Women undergoing embryo transfer cycles, in which at least 1 good-quality embryo was transferred. INTERVENTION(S): Collection of cervical secretions during the procedure of embryo transfer. MAIN OUTCOME MEASURE(S): Methylation profiles of cervical secretions in relation to pregnancy outcomes. RESULT(S): Genome-wide methylation profiles differ between cervical secretions from pregnancy and nonpregnancy cycles. Clustering analysis on the basis of the top 2,000 differentially methylated probes of cervical secretions from 28 pregnancy and 29 nonpregnancy cycles correctly categorized 86.0% of the samples in terms of conceptional status, which was verified in selected genes by quantitative methylation-specific polymerase chain reaction and validated in another independent sample set. The combination of selected genes was estimated to predict pregnancy outcomes with a maximal area under the receiver operating characteristic curve of 0.83. CONCLUSION(S): The methylation profiles of cervical secretions were associated with pregnancy outcomes in embryo transfer cycles. Although not clinically useful at present, deoxyribonucleic acid methylation in cervical secretions may shed new light on the less invasive assessment of endometrial receptivity.

Exploring factors influencing the work-related morale for certified nursing assistants in hospice care: A structural equation modeling study.

BACKGROUND: Certified nursing assistants (CNAs) in palliative care units often encounter the death of patients and undergo emotional burdens because of their altruistic practices. However, the influences of altruism and perceptions of death on the work morale of CNAs remain unclear. The fact that morale can be improved by modifying related factors justifies the necessity of a theoretical model of morale for CNAs. However, such a model is currently absent. Based on relevant literature, factors including altruism, social support, perceptions of death, and job satisfaction are related to morale through the mediation of job stress. AIM: This study was aimed toward determining the influencing factors and developing a structural model of morale with regard to CNAs working in palliative care units. DESIGN: The hypothesized model was tested in a cross-sectional design with structural equation modeling using AMOS 23. SETTING/PARTICIPANTS: A total of 413 CNAs from five hospice units in Taiwan participated in the survey. RESULTS: Goodness-of-fit indexes, including χ2/DF = 2.187, PGFI = 0.461, and PNFI = 0.462, among others, confirmed the modified model fit the data well. Altruism, social support, perceptions of death, and job satisfaction were negatively related to job stress (-0.238, -0.196, -0.204, and -0.131, respectively). Altruism and social support positively affected job satisfaction (0.635 and 0.553). Factors directly affecting morale included altruism, social support, job stress, and job satisfaction (0.837, 0.711, -0.244, and 0.540, respectively). The relationship between altruism and morale was the strongest among all the direct paths toward morale. Job stress was the major mediator in these relationships. CONCLUSION: Altruism is imperative for morale. The confirmed model is called the Five Constructs to Morale (5CM) model. These findings indicate the need to assess the levels of altruism and perceptions of death during the recruitment of CNAs. From the perspective of human resource management and organizational behavior, CNAs with a high level of altruism and a positive attitude toward death assure the well-being of end of life patients because of work involvement and commitment to the challenging work of hospice care. The cultivation of a supportive environment and coping strategies are suggested for the management of CNAs facing patient death. Hospice care decision makers should carefully assess morale levels among health professionals by applying the 5CM model. Identifying modifiable factors that can improve morale among nursing staff in hospice care to ensure work fulfillment and quality care merits emphasis in clinical practice. The establishment of effective strategies to facilitate the work morale of nursing staff is suggested for palliative care units. Morale improvement related task should be a global public health priority.

Investigation of time-dependent risk of mental disorders after infertility diagnosis, through survival analysis and data mining: a nationwide cohort study.

OBJECTIVES: Infertile patients are vulnerable to mental disorders. However, a time-dependent model predicting the onset of mental disorders specific to infertile patients is lacking. This study examined the risk factors for the development of mental disorders in infertile patients and measured the duration until the occurrence of mental disorders after a diagnosis of infertility. METHODS: A total of 13,317 infertile patients in the 2002-2013 Taiwan National Health Insurance Research Database were observed. The 11 independent variables included in the hypothesised model, together with the dates of infertility and mental disorder diagnoses, were analysed using Cox proportional hazards. Data-mining methods using C5.0 and Apriori supplemented the statistical analyses. RESULTS: The total prevalence rate of mental disorders among infertile patients in Taiwan was 12.41%, including anxiety (4.66%), depression (1.81%) and other mental disorders (5.94%). The average time interval for onset of mental illness identified using survival analysis was 1.67 years. Income, occupation, treatment method, co-morbidity, region and hospital level and ownership were significant predictors of development of mental illness (all p < .05). CONCLUSIONS: The four categories of factors associated with time-dependent onset were demographics, health, health care provider and geographical characteristics. Certain patient characteristics may predict a higher likelihood of onset of a specific mental disorder. Clinical practitioners may use the findings to identify high-risk patients and make timely health interventions.

High-throughput flowing upstream sperm sorting in a retarding flow field for human semen analysis.

In this paper, we propose a microfluidic device capable of generating a retarding flow field for the sorting and separation of human motile sperm in a high-throughput manner. The proposed sorting/separation process begins with a rapid flow field in a straight-flow zone to carry sperm into a sorting zone to maintain the sperm's mobility. The sorting zone consists of a diffuser-type sperm sorter to differentiate sperm with different motilities based on the flowing upstream nature of human sperm in a retarding flow field. The dead sperm will then be separated from the live ones by passing through a dumbbell flow field to the outlet for disposal. The proposed flowing upstream sperm sorter (FUSS) is designed to imitate the selection mechanism found in the female body when sperm swim into the uterus. The experimental results demonstrate the utility of this device with regard to throughput (approximately 200 000 sperm per minute and a maximum of 200 million cells per mL), efficiency (90% of selected sperm are mobile), and the ability to select sperm with high motility (∼20% of sperm with a velocity exceeding 120 µm s-1). The proposed device is suitable for intrauterine insemination as well as in vitro fertilization thanks to the highly efficient sorting process not interfering with the natural function and energy resource of human sperm.

Antimetastatic effects of cordycepin mediated by the inhibition of mitochondrial activity and estrogen-related receptor α in human ovarian carcinoma cells.

Cordycepin (3'-deoxyadenosine) is a compound for antitumor, which has been found to exert antiangiogenic, antimetastatic, and antiproliferative effects, as well as inducing apoptosis. However, the association between cancer metastasis and mitochondrial activity in cordycepin-treated ovarian carcinoma cells remains unclear. The 50 and 100 µM of cordycepin inhibits mitochondrial fusion and induces mitochondrial fission, respectively. These suggested that cordycepin showed the down-regulation of mitochondrial function and limitation of energy production. Because of activation of mitochondria and generation of energy are needed in cancer cell migration/invasion. After 24 h treatment, cordycepin suppresses epithelial-mesenchymal transition and migration in ovarian carcinoma cells through inhibiting estrogen-related receptor (ERR)-α. The ERRα is a co-transcription factor for gene expressions associated with mitochondrial fusion. Our results indicate that cordycepin suppresses metastasis and migration of ovarian carcinoma cells via inhibiting mitochondrial activity in non-toxic concentrations, and cordycepin has potential benefits in ovarian cancer therapy.

The inhibition of cordycepin on cancer stemness in TGF-beta induced chemo-resistant ovarian cancer cell.

Chemotherapy is one of the main approach for ovarian cancer. Cancer stem cells (CSCs) escape chemotherapy and lead to chemoresistance. We previously demonstrated that cordycepin (Cd) inhibited metastasis in human ovarian carcinoma cells, the aim of this study is to investigate the effects of Cd on ovarian cancer stemness. TGF-beta was used to induce chemoresistance of chemotherapeutic agent cisplatin in SKOV-3 ovarian cancer cells. After treating with 100 µM of Cd, cell viability, the percentage of cancer stem cells, and the levels of matrix metalloproteinases (MMPs) were decreased in TGF-beta-induced SKOV-3 cells. Treatment of Cd recovered E-cadherin levels and inhibited vimentin levels while TGF-beta treatment significantly increased the expression of vimentin and PGC-1alpha, and decreased E-cadherin levels in SKOV-3 cells, indicating that the action of Cd on cancer stemness may contribute to the regulation of epithelial-mesenchymal transition (EMT). Cd efficiently attenuated chemoresistance caused by TGF-beta in SKOV-3 cancer stem cells to promote the cytotoxicity of cisplatin.

Isoliquiritigenin induces apoptosis and autophagy and inhibits endometrial cancer growth in mice.

Endometrial cancer is the most common cancer in women, typically with onset after menopause. Isoliquiritigenin (ISL), a licorice flavonoid, was previously shown to have anti-oxidant, anti-inflammatory, and tumor suppression effects. In this study, we investigated the anti-tumor effect of ISL on human endometrial cancer both in vitro and in vivo. We used telomerase-immortalized human endometrial stromal cells (T-HESCs) and human endometrial cancer cell lines (Ishikawa, HEC-1A, and RL95-2 cells) as targets. The effects of ISL on cell proliferation, cell cycle regulation, and apoptosis or autophagy-related protein expression were examined. In addition, we conducted in vivo experiments to confirm the inhibitory effects of ISL on cancer cells. ISL significantly inhibited the viability of cancer cells in a dose- and time-dependent manner but with little toxicity on normal cells. In addition, flow cytometry analysis indicated that ISL induced sub-G1 or G2/M phase arrest. ISL treatment activated the extracellular signal regulated kinase signaling pathway to enhance the protein expression of caspase-7/LC3BII associated with apoptosis/autophagy. Furthermore, ISL suppressed xenograft tumor growth in vivo. Taken together, these findings suggest that ISL may induce apoptosis, autophagy, and cell growth inhibition, indicating its potential as a therapeutic agent for human endometrial cancer.

Aqueous Extract of Paris polyphylla (AEPP) Inhibits Ovarian Cancer via Suppression of Peroxisome Proliferator-Activated Receptor-Gamma Coactivator (PGC)-1alpha.

Chemotherapy, a major approach was used in carcinoma treatment, always involves the development of drug resistance as well as side-effects that affect the quality of patients' lives. An association between epithelial-mesenchymal transition (EMT) and chemotherapy resistance was established recently. We demonstrate in this paper that the aqueous extract of Paris polyphylla (AEPP)-a traditional Chinese medicine-can be used in various cancer types for suppression of carcinogenesis. We evaluated the suppressions of EMT and mitochondrial activity by AEPP treatment in a high-glucose (HG) induced-human ovarian carcinoma cell line (OVCAR-3 cells). The mitochondrial morphology was investigated using MitoTracker Deep Red FM staining. Our results indicated that AEPP reduced the viability of OVCAR-3 cells considerably through induction of apoptosis. However, this inhibitory potential of AEPP was attenuated by HG induction in OVCAR-3 cells. The levels of estrogen-related receptor (ERR)-alpha activator and peroxisome proliferator-activated receptor-gamma coactivator (PGC)-1alpha were elevated by HG induction, but were suppressed by AEPP treatment. Down-regulations of cell survival and EMT were oberved in OVCAR-3 cells through suppression of PGC-1alpha by AEPP treatment. These results were confirmed through PGC-1alpha knockdown and overexpression in OVCAR-3 cells. Thus, AEPP can be beneficial for treating ovarian cancer and has potential for development of an integrative cancer therapy against ovarian cancer proliferation, metastasis, and migration.

Anti-Cancer Activity of Solanum nigrum (AESN) through Suppression of Mitochondrial Function and Epithelial-Mesenchymal Transition (EMT) in Breast Cancer Cells.

Chemotherapy is the main approach for treating advanced and recurrent carcinoma, but the clinical performance of chemotherapy is limited by relatively low response rates, drug resistance, and adverse effects that severely affect the quality of life of patients. An association between epithelial-mesenchymal transition (EMT) and chemotherapy resistance has been investigated in recent studies. Our recent studies have found that the aqueous extract of Solanum nigrum (AESN) is a crucial ingredient in some traditional Chinese medicine formulas for treating various types of cancer patients and exhibits antitumor effects. We evaluated the suppression of EMT in MCF-7 breast cancer cells treated with AESN. The mitochondrial morphology was investigated using Mitotracker Deep-Red FM stain. Our results indicated that AESN markedly inhibited cell viability of MCF-7 breast cancer cells through apoptosis induction and cell cycle arrest mediated by activation of caspase-3 and production of reactive oxygen species. Furthermore, mitochondrial fission was observed in MCF-7 breast cancer cells treated with AESN. In addition to elevation of E-cadherin, downregulations of ZEB1, N-cadherin, and vimentin were found in AESN-treated MCF-7 breast cancer cells. These results suggested that AESN could inhibit EMT of MCF-7 breast cancer cells mediated by attenuation of mitochondrial function. AESN could be potentially beneficial in treating breast cancer cells, and may be of interest for future studies in developing integrative cancer therapy against proliferation, metastasis, and migration of breast cancer cells.

Solanum nigrum Protects against Hepatic Fibrosis via Suppression of Hyperglycemia in High-Fat/Ethanol Diet-Induced Rats.

BACKGROUND: Advanced glycation end products (AGEs) signal through the receptor for AGE (RAGE), which can lead to hepatic fibrosis in hyperglycemia and hyperlipidemia. We investigated the inhibitory effect of aqueous extracts from Solanum nigrum (AESN) on AGEs-induced RAGE signaling and activation of hepatic stellate cells (HSCs) and hyperglycemia induced by high-fat diet with ethanol. METHODS: An animal model was used to evaluate the anti-hepatic fibrosis activity of AESN in rats fed a high-fat diet (HFD; 30%) with ethanol (10%). Male Wistar rats (4 weeks of age) were randomly divided into four groups (n = 6): (1) control (basal diet); (2) HFD (30%) + ethanol (10%) (HFD/ethanol); (3) HFD/ethanol + AESN (100 mg/kg, oral administration); and (4) HFD/ethanol + pioglitazone (10 mg/kg, oral administration) and treated with HFD for 6 months in the presence or absence of 10% ethanol in dietary water. RESULTS: We found that AESN improved insulin resistance and hyperinsulinemia, and downregulated lipogenesis via regulation of the peroxisome proliferator-activated receptor α (PPARα), PPARγ co-activator (PGC-1α), carbohydrate response element-binding protein (ChREBP), acetyl-CoA carboxylase (ACC), and fatty acid synthase (FAS) mRNA levels in the liver of HFD/ethanol-treated rats. In turn, AESN may delay and inhibit the progression of hepatic fibrosis, including α-smooth muscle actin (α-SMA) inhibition and MMP-2 production. CONCLUSIONS: These results suggest that AESN may be further explored as a novel anti-fibrotic strategy for the prevention of liver disease.

Impact of the number of retrieved oocytes on pregnancy outcome in in vitro fertilization.

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.

Investigating the Relationships among Stressors, Stress Level, and Mental Symptoms for Infertile Patients: A Structural Equation Modeling Approach.

OBJECTIVE: Patients with infertility are a high risk group in depression and anxiety. However, an existing theoretically and empirically validated model of stressors, stress, and mental symptoms specific for infertile patients is still a void. This study aimed to determine the related factors and their relational structures that affect the level of depressive and anxiety symptoms among infertile patients. METHODS: A cross-sectional sample of 400 infertility outpatients seeking reproduction treatments in three teaching hospitals across Taiwan participated in the structured questionnaire survey in 2011. The hypothesized model comprising 10 latent variables was tested by Structural Equation Modeling using AMOS 17. RESULTS: Goodness-of-fit indexes, including χ2/DF = 1.871, PGFI = 0.746, PNFI = 0.764, and others, confirmed the modified model fit the data well. Marital stressor, importance of children, guilt-and-blame, and social stressor showed a direct effect on perceived stress. Instead of being a factor of stress, social support was directly and positively related to self-esteem. Perceived stress and self-esteem were the two major mediators for the relationships between stressors and mental symptoms. Increase in social support and self-esteem led to decrease in mental symptoms among the infertile patients. CONCLUSIONS: The relational structures were identified and named as the Stressors Stress Symptoms Model, clinically applied to predict anxiety and depression from various stressors. Assessing sources and level of infertility-related stress and implementing culturally-sensitive counseling with an emphasis on positive personal value may assist in preventing the severity of depression and anxiety.

Cisplatin-, Doxorubicin-, and Docetaxel-Induced Cell Death Promoted by the Aqueous Extract of Solanum nigrum in Human Ovarian Carcinoma Cells.

Chemotherapy is a major clinical treatment for managing patients with advanced and recurrent ovarian cancer. However, the clinical performance of chemotherapy is limited, and adverse effects have been observed. Integrating chemotherapy with current chemotherapeutic drugs and novel antitumor ingredients might improve the clinical performance of current chemotherapy for ovarian cancer. The aqueous extract of Solanum nigrum leaves (AE-SN), a key ingredient in many traditional Chinese medicine formulae, has exhibited tumor suppression efficacy in numerous human cancer cells but not in ovarian cancer cells. In this study, tumor suppression efficacy was determined using the ES-2, SKOV-3, and OVCAR-3 human ovarian cancer cell lines. The half-maximal inhibitory concentrations of the AE-SN in ES-2 and SKOV-3 cells were 1.052 and 1.779 mg/mL, respectively. AE-SN treatment increased the accumulation of mammalian microtubule-associated protein 1 light chain 3 A/B, an autophagic cell marker, in all the tested cell lines; however, it activated the cleavage of caspase-3, an apoptotic marker, only in SKOV-3 cells. Furthermore, the AE-SN also promoted tumor suppression efficiency of cisplatin, doxorubicin, and docetaxel in the tested ovarian cancer cells. In addition, AE-SN-enhanced cell death was associated with AE-SN-induced caspase-3 cleavage in SKOV-3 cells. In conclusion, the AE-SN exhibited tumor suppression efficacy and improved the tumor suppression efficiency of cisplatin, doxorubicin, and docetaxel in human ovarian cancer cells. Therefore, the AE-SN is a candidate antitumor ingredient that can be used in developing future integrated chemotherapy for managing ovarian cancer.

Preclinical evaluation on the tumor suppression efficiency and combination drug effects of fermented wheat germ extract in human ovarian carcinoma cells.

Fermented wheat germ extract (FWGE) is a nutrient supplement and a potential antitumor ingredient for developing an integrated chemotherapy with standard chemotherapeutic drugs for treating ovarian cancer patients. In this study, we evaluated the tumor suppression efficiency of FWGE in human ovarian carcinoma cells, SKOV-3 and ES-2, and found the half-maximal inhibitory concentrations (IC50s) to be 643.76 µg/mL and 246.11 µg/mL after 48 h of FWGE treatment. FWGE treatment also induced programmed cell death by activating the caspase-7 cleavage in both SKOV-3 and ES-2 cells, but only caspase-3 and poly(adenosine diphosphate-ribose) polymerase cleavages were activated in SKOV-3 cells. Moreover, FWGE exhibited combination drug effects with cisplatin and docetaxel in SKOV-3 and ES-2 cells by enhancing the cytotoxicity of both drugs. In conclusion, we found that FWGE not only suppressed cell growth but also induced caspase-3-related and caspase-7-related cell death in human ovarian carcinoma cells. FWGE treatment further enhanced the cytotoxicity of cisplatin and docetaxel, suggesting that FWGE is a potential ingredient in the development of adjuvant chemotherapy with cisplatin or docetaxel for treating ovarian cancer patients.

Targeted anti-apoptosis activity for ovarian protection against chemotherapy-induced ovarian gonadotoxicity.

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.

Antitumor Effects and Biological Mechanism of Action of the Aqueous Extract of the Camptotheca acuminata Fruit in Human Endometrial Carcinoma Cells.

The aqueous extracts of the leaves and fruit of Camptotheca acuminata have long been used in traditional Chinese medicine (TCM) for treating cancer patients. The chemotherapeutic drug, camptothecin (CPT), and related analogs were first isolated from C. acuminata in the 1970s. Although the antitumor effects of CPT have been characterized in recent years, the antitumor effects of aqueous extracts of C. acuminata have not been clarified. The aims of our current study were to determine the tumor-suppression efficiency of an aqueous extract of the fruit of C. acuminata (AE-CA) in the human endometrial carcinoma cell lines, HEC-1A, HEC-1B, and KLE, and compare its antitumor effects with those of CPT. Cell viability assays indicated that a dosage of AE-CA containing 0.28 mg/mL of CPT demonstrated enhanced cytotoxicity, compared with CPT treatment. The effects of AE-CA on the induction of cell cycle arrest, the accumulation of cyclin-A2 and -B1, and the activation of caspase-3 and caspase-7 were similar to those of CPT. Furthermore, AE-CA exhibited a synergistic effect on the cytotoxicity of cisplatin in HEC-1A and HEC-1B cells. These results indicated that AE-CA is a potent antitumor agent and can be combined with cisplatin for the treatment of human endometrial cancer.

Cluster analysis of cardiovascular and metabolic risk factors in women of reproductive age.

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.

Oligohydramnios increases the risk of respiratory hospitalization in childhood: a population-based study.

BACKGROUND: Pulmonary hypoplasia is associated with reduced lung function in infancy. The aim of this study was to evaluate the hypothesis that children exposed to oligohydramnios display an increased risk of hospitalization for respiratory illness by using a population-based matched-cohort design. METHODS: We used three nationwide population-based data sets to identify 5,228 women who gave birth during 2004 to 2007 and were diagnosed with oligohydramnios during the third trimester of pregnancy. A cohort of 20,912 unaffected pregnant women was matched with these cases, according to neonatal sex and gestational age, maternal age and education, and level of prenatal care. Respiratory hospitalization and respiratory failure were defined using discharge diagnostic codes. RESULTS: Oligohydramnios-exposed children had an 8% higher incidence rate of respiratory hospitalization and an 80% higher incidence rate of respiratory failure, compared with children without oligohydramnios exposure. This risk remained after adjusting for all potential risk factors. Cox regression analyses indicated that the adjusted hazard ratios of respiratory hospitalization and respiratory failure were 1.07 (95% confidence interval (CI): 1.01-1.15; P = 0.030) and 2.20 (95% CI: 1.26-3.84; P = 0.005), respectively. CONCLUSION: Children exposed to oligohydramnios during the third trimester of pregnancy display an increased risk of hospitalization for respiratory illness.

Antiapoptotic agent sphingosine-1-phosphate protects vitrified murine ovarian grafts.

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.