miRNA-34c-5p inhibits amphiregulin-induced ovarian cancer stemness and drug resistance via downregulation of the AREG-EGFR-ERK pathway.

Epithelial ovarian cancer is the most lethal gynecological cancer mainly due to late diagnosis, easy spreading and rapid development of chemoresistance. Cancer stem cells are considered to be one of the main mechanisms for chemoresistance, as well as metastasis and recurrent disease. To explore the stemness characteristics of ovarian cancer stem cells, we successfully enriched ovarian cancer stem-like cells from an established ovarian cancer cell line (SKOV-I6) and a fresh ovarian tumor-derived cell line (OVS1). These ovarian cancer stem-like cells possess important cancer stemness characteristics including sphere-forming and self-renewing abilities, expressing important ovarian cancer stem cell and epithelial-mesenchymal transition markers, as well as increased drug resistance and potent tumorigenicity. Microarray analysis of OVS1-derived sphere cells revealed increased expression of amphiregulin (AREG) and decreased expression of its conserved regulatory microRNA, miR-34c-5p, when compared with the OVS1 parental cells. Overexpression of AREG and decreased miR-34c-5p expression in SKOV-I6 and OVS1 sphere cells were confirmed by quantitative real-time PCR analysis. Luciferase reporter assay and mutant analysis confirmed that AREG is a direct target of miR-34c-5p. Furthermore, AREG-mediated increase of sphere formation, drug resistance toward docetaxel and carboplatin, as well as tumorigenicity of SKOV-I6 and OVS1 cells could be abrogated by miR-34c-5p. We further demonstrated that miR-34c-5p inhibited ovarian cancer stemness through downregulation of the AREG-EGFR-ERK pathway. Overexpression of AREG was found to be correlated with advanced ovarian cancer stages and poor prognosis. Taken together, our data suggest that AREG promotes ovarian cancer stemness and drug resistance via the AREG-EGFR-ERK pathway and this is inhibited by miR-34c-5p. Targeting AREG, miR-34c-5p could be a potential strategy for anti-cancer-stem cell therapy in ovarian cancer.

The impact of gestational diabetes mellitus on postpartum urinary incontinence: a longitudinal cohort study on singleton pregnancies.

OBJECTIVE: To determine whether gestational diabetes mellitus (GDM) is an independent risk factor for postpartum urinary incontinence in singleton pregnancies. DESIGN: A longitudinal cohort study. SETTING: A single tertiary-care hospital in Taiwan. POPULATION: Pregnant women with term deliveries between 2002 and 2007 (n = 6653) were consecutively recruited. METHODS: Logistic regression models were fitted based on generalised estimating equation methods to derive odds ratios for occurrences of type-specific urinary incontinence in the third trimester and at four time-points over 2 years during the postpartum period. MAIN OUTCOME MEASURES: Evaluation of whether GDM is an independent risk factor for postpartum urinary incontinence. RESULTS: The full model analysis revealed that GDM was an independent risk factor for all type-specific urinary incontinence (odds ratio [95% confidence interval]: 1.97 [1.56-2.51], 3.11 [2.18-4.43] and 2.73 [1.70-4.40] for stress, urge and mixed incontinence, respectively]. Compared with women without GDM, women with GDM tended to exhibit more severe symptoms of stress incontinence for up to 2 years postpartum, whereas for urge or mixed incontinence, more severe symptoms were found only for 6 months postpartum. Evaluation of quality of life using the Incontinence Impact Questionnaire 7 suggested that women with GDM requiring insulin treatment had a higher likelihood of functional impairment than women with GDM requiring conservative treatment only or women without GDM (P < 0.05, by the chi-square test for trend). CONCLUSIONS: GDM was found to be an independent risk factor for postpartum urinary incontinence and had a significant impact on quality of life. Women with GDM should be provided with timely consultation and support once urinary incontinence occurs.

Evolution of differential renal function after acute pyelonephritis.

(99m)Tc dimercaptosuccinic acid (DMSA) renal scans can provide accurate diagnosis of acute pyelonephritis, its sequelae (renal scars) and differential renal function (DRF). The purposes of this retrospective study were (1) to assess the relationship between DRF obtained during acute pyelonephritis and at follow-up, and (2) to elucidate the value of initial DRF in predicting subsequent renal scars. A total of 47 children were enrolled. All had both unilateral acute pyelonephritis diagnosed by initial DMSA renal scans, and follow-up DMSA renal scans. We found the correlation between initial and follow-up DRF poor (adjusted R2 = 0.396). Whether or not renal scars developed determined the follow-up DRF. Vesicoureteral reflux was significantly more common in children who developed renal scars. In addition, the higher the grade of vesicoureteral reflux, the lower the follow-up DRF and the improvement in DRF. When using a DRF of 46% as the cut-off value to predict subsequent renal scars, the sensitivity and specificity were 47.8% and 83.3%, respectively. Owing to the low sensitivity, initial DRF is not suitable for predicting the occurrence of renal scars.

Were there enough physicians in an emergency department in the affected area after a major earthquake? An analysis of the Taiwan Chi-Chi earthquake in 1999.

STUDY OBJECTIVE: The purpose of this study was to evaluate physician manpower and mobilization in an urban emergency department receiving patients after a major earthquake. METHODS: Patient charts were reviewed. The workload of physicians was assessed semiquantitatively before and after a major earthquake. The physicians' mobilization in the postearthquake emergency response was assessed by using a confidential questionnaire. RESULTS: In the 3 days after the earthquake, 566 patients with earthquake-related illnesses or injuries were sent to the urban ED. Three hundred one (53.2%) patients arrived within the initial 10 hours. In the initial hours, there was no significant difference between the number of patients per physician per hour before and after the earthquake. Workloads of wound treatment and advanced life support procedures were significantly higher after the earthquake compared with before the earthquake, during the first to sixth hour and second to fifth hour, respectively. Sixty-five percent of the hospital's physicians did not assist in either the ED or in any other parts of the hospital in the initial 6 hours after the earthquake. CONCLUSION: The number of physicians in the ED was insufficient in the initial hours after the earthquake because of the sudden influx of a large number of patients. Future disaster planning must address the issue of physicians' behavior with regard to their priorities immediately after a major earthquake and include greater provision for efficient mobilization of physicians.

Giant intraluminal fibrovascular polyp of the esophagus.

Giant polyps of the esophagus are relatively rare. Without previous history, the diagnosis of the disease is difficult to be made by esophagography and esophagoscopy. A case of giant intraluminal fibrovascular polyp (13x4x3.5 cm) of the esophagus is presented. The polyp was retrieved from the esophagus by a Foley's catheter and resected via the oral route.

Comparison of therapeutic efficacy of continuous ambulatory peritoneal dialysis between diabetic and non-diabetic patients: three years of experience.

To evaluate the therapeutic efficacy of continuous ambulatory peritoneal dialysis (CAPD) in diabetic uremic patients and compare it with that of non-diabetics, this study presents the results obtained from CAPD usage in a 3-year period. From December 1984 through December 1987, 12 non-insulin dependent diabetic patients (3 men and 9 women aged 65.5 +/- 3.4 years and with a treatment duration of 12.8 +/- 2.7 months, M +/- SE) and 11 non-diabetics (6 men and 5 women aged 45.0 +/- 5.3 years and with a treatment duration of 9.8 +/- 1.9 months) received CAPD treatment. In most of the patients, diabetes was complicated by significant cardiovascular diseases. None of them exchanged the CAPD bag by themselves. After CAPD treatment, subjective improvements were noted in both groups of patients but were more marked in the non-diabetic group. The BUN and creatinine levels were kept in an acceptable range except that higher creatinine levels were noted in the non-diabetic patients. Serum cholesterol levels rose mildly while triglyceride levels rose markedly in the diabetic patients. Albumin levels returned to normal in the non-diabetic group but remained low in the diabetic group. All patients except for one used the traditional subcutaneous route of insulin administration and blood sugar control was poor. The electrolyte profile was improved in both groups. The BP could be controlled but medication was still necessary. After CAPD most of the non-diabetic patients returned to their previous work while the diabetic patients remained dependent.(ABSTRACT TRUNCATED AT 250 WORDS)

Complement activation by iodinated contrast media.

Activation of the complement system by iodinated contrast medium (ICM) infusion was studied in 25 children with congenital heart disease who received 76% Urographin during angiocardiographic studies. Total hemolytic activity (CH50), C1q, C3, C4 and C3 activator were determined before and 2, 5, 10, 15 and 20 minutes after Urographin infusion. Results showed that CH50 decreased in 16 patients (64%), C3 in 12 patients (48%), C3 activator in 12 patients (48%), C1q in 11 patients (44%) and C4 in 11 patients (44%). No side effect was encountered in all patients. It is therefore concluded that both the classic and alternative complement pathways could be activated by ICM and no causal relationship could be found between the presence of complement activation and the occurrence of adverse reactions to ICM infusion.

Fabrication of optical waveguide taper couplers utilizing SiO(2).

The fabrication of optical waveguide couplers involving tapered layers of SiO(2) is discussed. Details of the photolithographic fabrication processing sequence are presented. This process utilizes carefully controlled etchant undercutting and has been found to be quite reproducible. It has allowed fabrication of tapers having changes in Sio(2) thickness of 1.0,microm over lengths of 55-75 microm. Results are presented which demonstrate taper transverse uniformity for distances of over 600,microm. The smoothness and gradual nature of the tapers are apparent in scanning electron microscope pictures of a taper cross section.