Pelvic organ prolapse in Caucasian and East Asian women: a comparative study.

OBJECTIVE: Ethnicity has been suggested to be a significant risk factor for pelvic organ prolapse (POP); yet, pelvic organ descent in different ethnic groups, especially in Asian populations, is not well studied. The aim of this study was to compare prolapse stages, pelvic organ descent and hiatal dimensions between East Asian and Caucasian women presenting with symptoms of POP. METHODS: This was a prospective observational study of East Asian and Caucasian women presenting with symptoms of POP to a tertiary urogynecology clinic in, respectively, Hong Kong and Sydney. Demographic data, prolapse symptoms and prolapse stage were assessed. Physical examination was performed using the pelvic organ prolapse quantification (POP-Q) system. All women underwent transperineal ultrasound using Voluson systems. Offline analysis of four-dimensional ultrasound volume data was performed at a later date, by one operator blinded to all clinical data, to ascertain pelvic organ descent and hiatal dimensions on Valsalva maneuver. Levator muscle avulsion was assessed in volumes obtained on pelvic floor muscle contraction. Multiple logistic regression analysis was performed to assess factors associated with prolapse on clinical and ultrasound examinations. RESULTS: A total of 225 East Asian women were included between July 2012 and February 2014 from the Hong Kong clinic and 206 Caucasian women between January 2015 and July 2016 from the Sydney clinic. There was no significant difference in the overall staging of prolapse. However, in East Asian women, compared with Caucasians, apical compartment prolapse was more common (99.6% vs 71.8%, P < 0.001) and posterior compartment prolapse less common (16.9% vs 48.5%, P < 0.001) on POP-Q examination. On Valsalva maneuver, the position of the uterus was lower in East Asian than in Caucasian women (-11.3 vs 1.35 mm, P < 0.001), while the rectal ampulla position was lower in Caucasians than in East Asians (-10.6 vs - 4.1 mm, P < 0.001). On multiple regression analysis, Caucasian ethnicity was a significant factor for lower risk of apical compartment prolapse on clinical assessment (odds ratio (OR), 0.01; P < 0.001) and on ultrasound (OR, 0.13; P < 0.001), and for a higher risk of posterior compartment prolapse on clinical assessment (OR, 4.36; P < 0.001) and of true rectocele on ultrasound (OR, 8.14; P < 0.001). CONCLUSIONS: East Asian women present more commonly with uterine prolapse while Caucasians show more often posterior compartment prolapse. Ethnicity was a significant predictor of type of prolapse on multivariate analysis. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.

Mesh-related complications from reconstructive surgery for pelvic organ prolapse in Chinese patients in Hong Kong.

INTRODUCTION: Mesh-related complications from reconstructive surgery for pelvic organ prolapse are of international concern. The present study aimed to review the incidence, management, and surgical outcomes of mesh-related complications in a Chinese population compared with existing studies involving Western populations. METHODS: This was an analysis of a prospectively collected cohort. Laparoscopic sacrocolpopexy, laparoscopic hystercolposacropexy, or transvaginal mesh surgery were offered with or without concomitant vaginal hysterectomy or continence surgery. Patients were followed up and mesh-related complications were noted. RESULTS: Overall, 276 Chinese women who received mesh surgery were included for data analysis. There were 22 mesh-related complications found during a mean follow-up period of 40 months. Mesh exposure accounted for 20 these complications; significantly more occurred after transvaginal than after abdominal mesh surgery (16 vs 4; P=0.01). Median duration from primary operation to the time of mesh exposure detection was 12 months (interquartile range=4.8-32.8 months). Ten patients required surgical excisions of exposed mesh. The re-operation rate after mesh complications was 6.7% (9/134) for transvaginal mesh surgery and 1.4% (2/142) for laparoscopic sacrocolpopexy (P=0.03). All excisions were performed transvaginally and 95% remained well after surgery. Occurrence of mesh exposure was higher in transvaginal mesh surgery (adjusted odds ratio=6.1; P=0.008), in sexually active patients (adjusted odds ratio=5.4; P=0.002), and in obese patients (adjusted odds ratio=3.7; P=0.046). Over 90% were satisfied with the outcome, regardless of mesh complications. CONCLUSIONS: The rates of mesh exposure and re-operation were consistent with those reported in the literature, suggesting no significant differences in outcome between Chinese and Western patients for this type of surgery.

Longitudinal pelvic floor biometry: which factors affect it?

OBJECTIVES: To evaluate pelvic floor biometry of women 3-5 years after their first delivery. The effect of a subsequent delivery and the mode of delivery on pelvic floor biometry were also studied. METHODS: Three-hundred and twenty-eight women who had been examined by translabial ultrasound during their first singleton pregnancy and at 8 weeks and 1 year postpartum, were invited for a follow-up 3-5 years later. The positions of the bladder neck, cervix, anorectal junction and hiatal area (HA) were evaluated using translabial ultrasound. The effects of parity, mode of delivery and levator ani muscle avulsion were studied. RESULTS: A total of 240 women completed the study. Of these, 179 had one or more vaginal deliveries (VD) (VD-only group), 52 had one or more Cesarean sections (CS) (CS-only group) and nine had both VD and CS at follow-up. The mean interval between the first delivery and follow-up was 3.8 years. A significantly lower bladder neck and anorectal junction on Valsalva, a lower cervix at rest, on Valsalva and pelvic floor muscle contraction, and a greater HA were observed in the VD-only group at follow-up, compared with findings at 1 year of follow-up or in the first pregnancy. The findings were similar in the CS-only group, except without a lower anorectal junction on Valsalva. Compared with the primiparous VD-only group, a greater HA at rest was observed in the multiparous VD-only group (P = 0.027). The VD-only group had a greater HA than the CS-only group. CONCLUSIONS: At 3-5 years after first delivery, a lower bladder neck, cervix and anorectal junction, and a greater HA were observed compared with findings in the first trimester and at 1 year of follow-up, regardless of parity or mode of delivery. Women with two or more VDs had a greater HA compared with those who had only one VD, and women with at least one VD had a greater HA compared with those who delivered by CS only. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

A loop of cancer-stroma-cancer interaction promotes peritoneal metastasis of ovarian cancer via TNFα-TGFα-EGFR.

Peritoneum is the most common site for ovarian cancer metastasis. Here we investigate how cancer epigenetics regulates reciprocal tumor-stromal interactions in peritoneal metastasis of ovarian cancer. Firstly, we find that omental stromal fibroblasts enhance colony formation of metastatic ovarian cancer cells, and de novo expression of transforming growth factor-alpha (TGF-α) is induced in stromal fibroblasts co-cultured with ovarian cancer cells. We also observed an over-expression of tumor necrosis factor-alpha (TNF-α) in ovarian cancer cells, which is regulated by promoter DNA hypomethylation as well as chromatin remodeling. Interestingly, this ovarian cancer-derived TNF-α induces TGF-α transcription in stromal fibroblasts through nuclear factor-κB (NF-κB). We further show that TGF-α secreted by stromal fibroblasts in turn promotes peritoneal metastasis of ovarian cancer through epidermal growth factor receptor (EGFR) signaling. Finally, we identify a TNFα-TGFα-EGFR interacting loop between tumor and stromal compartments of human omental metastases. Our results therefore demonstrate cancer epigenetics induces a loop of cancer-stroma-cancer interaction in omental microenvironment that promotes peritoneal metastasis of ovarian cancer cells via TNFα-TGFα-EGFR.

Levator ani muscle avulsion is a risk factor for expulsion within 1 year of vaginal pessary placed for pelvic organ prolapse.

OBJECTIVE: The aim of this study was to investigate whether the presence of levator ani muscle (LAM) avulsion is associated with expulsion within 1 year of a vaginal pessary placed for pelvic organ prolapse (POP). METHODS: This was a prospective observational study of consecutive women with symptomatic POP, who had not received treatment for the condition before the consultation and opted for vaginal pessary placement in our center. Volume acquisition was performed before pessary insertion and offline analysis of the 3D/4D transperineal ultrasound volume data was performed. LAM was assessed on maximum pelvic floor muscle contraction (PFMC) and hiatal dimensions were assessed at rest, on PFMC and on maximum Valsalva. Results were compared between women in whom the pessary was retained for 1 year and those in whom the pessary was expelled within 1 year. RESULTS: The datasets of 255 women were analyzed including 147 (57.6%) women who had a vaginal pessary continuously in place over 1 year and 108 (42.4%) with pessary expulsion. Mean age was 63.2 (SD, 9.9) years and median parity was 3 (2-4). Eighteen (7.1%) had Stage I, 164 (64.3%) Stage II, 67 (26.3%) Stage III and six (2.4%) Stage IV POP. Women with vaginal pessary expulsion within 1 year had significantly larger hiatal dimensions at rest and on Valsalva, larger hiatal area during rest, PFMC and Valsalva and higher rate of LAM avulsion (53.7% vs 27.2%, P < 0.01) compared with women in whom the pessary was retained for 1 year. After controlling for potential confounders, LAM avulsion remained a risk factor (OR, 3.18, P < 0.01) of vaginal pessary expulsion within 1 year. CONCLUSIONS: Women in whom a vaginal pessary was expelled within 1 year of placement for POP had a larger hiatus. Presence of LAM avulsion was associated with a three-fold increase in the risk of expulsion of a vaginal pessary within 1 year. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

Longitudinal follow-up of levator ani muscle avulsion: does a second delivery affect it?

OBJECTIVES: To evaluate the morphological outcome of levator ani muscle (LAM) avulsion 3-5 years after a first delivery and to assess the effect of a second delivery on this condition. The impact of LAM avulsion on pelvic floor disorders was also studied. METHODS: Six hundred and sixty-six women who had been assessed for LAM avulsion 8 weeks after their first delivery were invited for a follow-up examination 3-5 years later. Women completed the Pelvic Floor Distress Inventory including the Urinary Distress Inventory (UDI) and Pelvic Organ Prolapse Distress Inventory (POPDI) questionnaires to explore symptoms of pelvic floor disorders, and the pelvic floor was examined using three-dimensional translabial ultrasound and assessed using the pelvic organ prolapse quantification system. RESULTS: Three hundred and ninety-nine women completed the study, of whom 151 were multiparous. Mean interval between first delivery and follow-up was 42.3 ± 7.6 months. Among 69 women who had LAM avulsion 8 weeks after their first delivery, nine (13.0%) had no LAM avulsion at follow-up. One (0.9%) woman had a new LAM avulsion after her second vaginal delivery. A greater proportion of women with LAM avulsion reported symptoms of stress urinary incontinence (SUI) (adjusted odds ratio, 2.09 (95% CI, 1.18-3.70); P = 0.01) and symptoms of prolapse than did women without avulsion; however, this difference did not reach statistical significance (P = 0.61). Women with LAM avulsion had higher UDI and POPDI scores than did women without avulsion (median UDI score, 17.7 (interquartile range (IQR), 5.0-32.4) vs 9.2 (IQR, 0.0-22.1); P = 0.045 and median POPDI score, 20.8 (IQR, 8.8-40.5) vs 10.7 (IQR, 0.0-32.8); P = 0.021). CONCLUSIONS: The risk of developing new LAM avulsion after a second vaginal delivery is low (0.9%). Healing of LAM avulsion was observed in 13% of women who had at least one vaginal delivery. At 3-5 years after delivery, women with LAM avulsion reported symptoms of SUI more often than did those without, and had higher UDI and POPDI scores, implying more bothersome symptoms. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

Antenatal pelvic floor biometry is related to levator ani muscle injury.

OBJECTIVE: To evaluate the relationship between antenatal pelvic floor biometry and levator ani muscle (LAM) injury in Chinese women. METHODS: Three-dimensional transperineal ultrasound was performed in nulliparous Chinese women with a singleton pregnancy at 9-12 weeks, 26-28 weeks and 36-38 weeks of gestation and again at 12 months after delivery. Hiatal anteroposterior (AP) diameter, transverse diameter and area were measured on the antenatal ultrasound volumes obtained at rest, on Valsalva maneuver and during pelvic floor muscle contraction (PFMC). LAM injury was evaluated using ultrasound volumes obtained during PFMC at 12 months after delivery. RESULTS: In total, 328 women completed the study. At 12 months after delivery, 38 (14.8% of those who delivered vaginally) women had LAM injury; 28 were unilateral (14 right- and 14 left-sided) and 10 were bilateral. In all three trimesters there was smaller hiatal AP diameter and hiatal area in women with LAM injury when compared with women without injury. On multivariable analysis of the three factors, hiatal AP diameter at rest, hiatal area at rest and operative vaginal delivery, only hiatal AP diameter at rest in all three trimesters was an independent factor of LAM injury. A larger hiatal AP diameter at rest in the first, second and third trimesters reduced the likelihood of LAM injury with odds ratios of 0.21, 0.15 and 0.21, respectively. CONCLUSIONS: A smaller antenatal hiatal AP diameter at rest is a risk factor for LAM injury. The hiatal AP diameter is relatively simple to measure and the error in measurement is relatively small. A prospective study to confirm this relationship and to explore whether this measurement, performed in the midsagittal plane, is repeatable should be performed. Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd.

Phase I dose-escalating trial of Escherichia coli purine nucleoside phosphorylase and fludarabine gene therapy for advanced solid tumors.

BACKGROUND: The use of Escherichia coli purine nucleoside phosphorylase (PNP) to activate fludarabine has demonstrated safety and antitumor activity during preclinical analysis and has been approved for clinical investigation. PATIENTS AND METHODS: A first-in-human phase I clinical trial (NCT 01310179; IND 14271) was initiated to evaluate safety and efficacy of an intratumoral injection of adenoviral vector expressing E. coli PNP in combination with intravenous fludarabine for the treatment of solid tumors. The study was designed with escalating doses of fludarabine in the first three cohorts (15, 45, and 75 mg/m(2)) and escalating virus in the fourth (10(11)-10(12) viral particles, VP). RESULTS: All 12 study subjects completed therapy without dose-limiting toxicity. Tumor size change from baseline to final measurement demonstrated a dose-dependent response, with 5 of 6 patients in cohorts 3 and 4 achieving significant tumor regression compared with 0 responsive subjects in cohorts 1 and 2. The overall adverse event rate was not dose-dependent. Most common adverse events included pain at the viral injection site (92%), drainage/itching/burning (50%), fatigue (50%), and fever/chills/influenza-like symptoms (42%). Analysis of serum confirmed the lack of systemic exposure to fluoroadenine. Antibody response to adenovirus was detected in two patients, suggesting that neutralizing immune response is not a barrier to efficacy. CONCLUSIONS: This first-in-human clinical trial found that localized generation of fluoroadenine within tumor tissues using E. coli PNP and fludarabine is safe and effective. The pronounced effect on tumor volume after a single treatment cycle suggests that phase II studies are warranted. CLINICALTRIALSGOV IDENTIFIER: NCT01310179.

Pelvic floor muscle biometry and pelvic organ mobility in East Asian and Caucasian nulliparae.

OBJECTIVE: To compare the differences in levator ani muscle biometry and hiatal dimensions between pregnant nulliparous Caucasian and East Asian women. METHODS: Offline analysis of three/four-dimensional ultrasound volume data obtained from two groups of pregnant nulliparous women, Caucasian and East Asian, was performed. Volume acquisition was performed in the late third trimester using the same method in both groups, in the context of two prospective observational studies with identical entry criteria. Pelvic organ descent and levator hiatal dimensions were assessed using the volumes acquired on Valsalva maneuver, and pubovisceral muscle thickness was measured from the volumes obtained on pelvic floor muscle contraction (PFMC). RESULTS: Datasets of 200 East Asian and 168 Caucasian women were analyzed. Compared with Caucasian women, East Asian women had a significantly lower body mass index. All indices of pelvic organ descent were significantly higher in the Caucasian group than in the East Asian group. The difference, expressed as a percentage, in levator hiatal area on both Valsalva maneuver and PFMC was markedly greater in Caucasian (32% vs. 19%; P < 0.001) than in East Asian (24% vs. 20%; P = 0.01) women. After controlling for potential confounders using multivariate regression analysis, racial origin remained the only significant factor associated with differences in pelvic organ descent and hiatal dimensions. The thickness and area of pubovisceral muscle were significantly higher in the East Asian group. CONCLUSIONS: Pregnant women of East Asian racial origin have a thicker pubovisceral muscle, smaller hiatus and less mobility of pelvic organs than do pregnant Caucasian women.

Prevalence of levator ani muscle injury and health-related quality of life in primiparous Chinese women after instrumental delivery.

OBJECTIVES: Levator ani muscle (LAM) injury is common after first vaginal delivery, and a higher incidence is associated with instrumental delivery. This study was conducted to compare the incidence of LAM injury after forceps or ventouse extraction in primiparous Chinese women, and to study their subsequent health-related quality of life. METHODS: This prospective observational study was conducted between 1 September 2011 and 31 May 2012 in a tertiary obstetric unit. All eligible primiparous women who had undergone instrumental delivery were recruited 1 to 3 days following delivery. The subjects completed the Pelvic Floor Distress Inventory questionnaire and Pelvic Floor Impact Questionnaire, and translabial ultrasound was performed 8 weeks' postpartum to determine whether the subjects had suffered LAM injury. RESULTS: Among the 289 women who completed the study, 247 (85.5%) had ventouse extraction and 42 (14.5%) had forceps delivery. Subsequent translabial ultrasound identified a total of 58 women with LAM injury. The prevalence of LAM injury after ventouse extraction and forceps delivery was 16.6% (95% CI, 12.0-21.2%) (41/247) and 40.5% (95% CI, 25.6-55.4%) (17/42), respectively (P = 0.001). Forceps delivery was identified as a risk factor for LAM injury, with an odds ratio of 3.54. No statistically significant differences were observed between the quality of life in women who underwent ventouse extraction and those with forceps delivery or between the quality of life in women with a unilateral or bilateral LAM injury. CONCLUSIONS: In our cohort of primiparous Chinese women, 20.1% (58/289) had LAM injury after instrumental delivery, and forceps delivery was identified as the only risk factor.

The impact of supportive counselling on women's psychological wellbeing after miscarriage--a randomised controlled trial.

OBJECTIVE: To assess the effectiveness of supportive counselling after miscarriage. DESIGN: Randomised controlled trial. SETTING: University hospital. SAMPLE: Two hundred and eighty women with miscarriage. METHOD: Women were randomised to receive supportive counselling from a nurse (at diagnosis and 2 weeks later) or routine care. Psychological wellbeing was measured with the General Health Questionnaire (GHQ-12) and Beck Depression Inventory (BDI). MAIN OUTCOME MEASURES: Primary outcome measured the proportion of women suffering psychological distress (GHQ-12 score ≥4) at 3 months after miscarriage. Secondary outcomes were GHQ-12 and BDI scores at 6 weeks, 3 and 6 months. RESULTS: There was no difference in the proportion of women suffering psychological distress at 3 months after miscarriage (17.1% in counselling group versus 24.4% in control group; 95% CI -0.034 to 0.177; P = 0.19). However, for the subgroup of women (n = 152) with high baseline GHQ-12 scores, the median GHQ-12 score in the counselling group was significantly lower than the control group at 6 weeks (median score 3 versus 4.5 in counselling and control groups; P = 0.04) and 3 months (median score 1 versus 2.5 in counselling and control groups; P = 0.03). Similarly, for women with high baseline BDI scores (BDI > 12), the proportion for women continuing to score high was significantly lower in the counselling group 6 weeks after miscarriage (33.3 versus 61.1% in counselling group and control group; P = 0.03). CONCLUSIONS: Although the results of current study do not justify routine counselling of all women following miscarriage, a supportive counselling programme for selected women with high levels of psychological distress is promising and merits further investigation.

Pelvic floor biometry in Chinese primiparous women 1 year after delivery: a prospective observational study.

OBJECTIVES: To evaluate pelvic floor biometry in Chinese women 1 year following childbirth and to explore factors that affect it. METHODS: Translabial ultrasound examination was performed at rest, on Valsalva maneuver (VM) and on pelvic floor muscle contraction (PFMC) in the first, second and third trimesters of pregnancy and at 8 weeks, 6 months and 12 months after delivery in a cohort of women delivering at term their first child. Offline analysis was undertaken to measure the position of the bladder neck, cervix, anorectal junction and hiatal dimensions at each posture and at each visit, and to detect levator ani muscle (LAM) injury on PFMC 8 weeks and 12 months after delivery. Results were analyzed according to mode of delivery. RESULTS: We recruited 442 women, of whom 328 (74.2%) completed the study; there was LAM injury in 48 women at 8 weeks and in only 38 women at 12 months. When comparing first-trimester biometry to that at 12 months after delivery, the bladder neck was more distal on VM and bladder neck displacement was increased, and the cervix was lower at rest and on VM in the vaginal delivery group. In the Cesarean section group, bladder neck and anorectal junction were more distal on VM, the cervix was lower at rest, on VM and on PFMC, and the hiatal area was increased on VM. There was a greater increase in hiatal area after vaginal delivery. Overall, 34.8% had irreversible hiatal distension (> 20% increase in hiatal area after delivery as compared to first trimester). LAM injury was significantly associated with irreversible hiatal distension (odds ratios, 5.2-9.5 at different postures). CONCLUSIONS: Pregnancy beyond 35 weeks of gestation has an effect on the pelvic floor of Chinese women, irrespective of mode of delivery. The pelvic organs remain more mobile after delivery when compared to in the first trimester, and there is no clear difference between the findings observed following vaginal delivery or Cesarean section, except in hiatal distension, which is greater after vaginal delivery. LAM injury is the factor most strongly associated with irreversible hiatal distension.

Effect of microbial phytase on phytate P degradation and apparent digestibility of total P and Ca throughout the gastrointestinal tract of the growing pig.

The effect of a dietary microbial phytase on mineral digestibility throughout the gastrointestinal tract (GIT) of the growing pig was studied. Thirty-two entire male pigs (~22 kg BW) were allocated equally to 4 corn-soybean meal diets. One diet was adequate in total P and Ca, the second diet was deficient in total P and Ca (low-P diet), and the third and fourth diets were the low-P diet with microbial phytase added at 1,107 U/kg or 2,215 U/kg, respectively. Titanium dioxide (3 g/kg) was included in the diets as an indigestible marker. The pigs were fed their respective diets for 42 d. Fecal samples were collected from d 38 to 41 and stomach chyme, terminal jejunal, and terminal ileal digesta samples were collected after euthanasia on d 42. Phytate P degradability and apparent total P and Ca digestibility were determined at the gastric, jejunal, ileal, and total tract levels. Phytate P degradation and apparent total P and Ca digestibility were not significantly different between the 2 microbial phytase inclusion levels. Across both microbial phytase-low-P diets, phytase supplementation increased (P < 0.05) phytate P degradability at the jejunal, ileal, and total tract levels by 101%, 77%, and 10%, respectively, but not at the gastric level. Total tract phytate P degradation was greater (P < 0.05) than ileal phytate P degradation for both the unsupplemented (52% units greater) and phytase-supplemented, low-P (26% units greater) diets. The latter result was not reflected by the apparent total P digestibility estimate, which was not significantly different between the ileal and total tract levels for both the unsupplemented and phytase-supplemented, low-P diets. Consequently, there appeared to be considerable phytate degradation in the hindgut, presumably due to the action of hindgut microbes, but the phytate P released in the hindgut did not appear to be absorbed. Apparent Ca digestibility was not significantly different among jejunal, ileal, and total tract levels for any of the dietary treatments, but apparent Ca digestibility was greater (P < 0.05) for the phytase-supplemented diets compared with the unsupplemented diets. Overall, dietary microbial phytase supplementation led to greater phytate degradation to the end of the jejunum. Because the phytate P released in the hindgut was not absorbed, ileal estimates, rather than total tract estimates, of phytate degradation appear to more accurately reflect P availability.

Pelvic floor biometry during a first singleton pregnancy and the relationship with symptoms of pelvic floor disorders: a prospective observational study.

OBJECTIVE: To assess pelvic floor biometry during pregnancy and the correlation with symptoms of pelvic floor disorders in women. DESIGN: A prospective observational study. SETTING: Antenatal clinic between August 2009 and May 2011. POPULATION: Nulliparous women in their first pregnancy. METHODS: Pelvic floor was assessed by translabial ultrasound and symptoms of pelvic floor disorders were explored with a standardised questionnaire at each trimester. MAIN OUTCOME MEASURES: Pelvic floor biometry during pregnancy. RESULTS: A total of 405 (91.6%) women completed the study. As the pregnancy advanced, there was significant descent of the bladder neck (BN), cervix, and anorectal junction. The hiatal area (HA) was significantly enlarged, with a mean increase of 15.1 ± 24.8% at rest, and 24.7 ± 28.5% at Valsalva, at third trimester when compared with first trimester. Risk factors for stress urinary incontinence (SUI) were: descent of BN at Valsalva (OR 3.2, 95% CI 1.2-8.5), increase in HA at pelvic floor contraction (PFMC; OR 1.3, 95% CI 1.0-1.6), and increase in maternal age (OR 1.1, 95% CI 1.0-1.2), at first trimester; increase in HA at PFMC (OR 1.3, 95% CI 1.1-1.5) at second trimester; and descent of BN at rest (OR 2.3, 95% CI 1.1-4.9) and increase in maternal age (OR 1.1, 95% CI 1.02-1.2) at third trimester. Descent of anorectal junction (OR 1.5, 95% CI 1.1-1.9) and increase in HA at rest (OR 1.2, 95% CI 1.0-1.3) were factors for prolapse symptoms at second and third trimester, respectively. CONCLUSIONS: Pelvic floor changes begin during pregnancy. There was significant descent of the BN, cervix, and anorectal junction, and enlargement of the hiatal area, as the pregnancy advanced. SUI was associated with descent of the BN, and prolapse symptoms were associated with an increase in the hiatal area.

Improvement of maternal vitamin D status with 25-hydroxycholecalciferol positively impacts porcine fetal skeletal muscle development and myoblast activity.

There is little information available regarding the influence of maternal vitamin D status on fetal skeletal muscle development. Therefore, we investigated the effect of improved vitamin D status resulting from 25-hydroxycholecalciferol (25OHD3) supplementation of dams on fetal skeletal muscle developmental characteristics and myoblast activity using Camborough 22 gilts (n = 40) randomly assigned to 1 of 2 corn-soybean meal-based diets. The control diet (CTL) contained 2,500 IU cholecalciferol (D3)/kg diet, whereas the experimental diet contained 500 IU D3/kg diet plus 50 µg 25OHD3/kg diet. Gilts were fed 2.7 kg of their assigned diet once daily beginning 43 d before breeding through d 90 of gestation. On gestational d 90 (± 1), fetal LM and semitendinosus muscle samples were collected for analysis of developmental characteristics and myoblast activity, respectively. No treatment difference was observed in fetal LM cross-sectional area (P = 0.25). Fetuses from 25OHD3-supplemented gilts had more LM fibers (P = 0.04) that tended to be smaller in cross-sectional area compared with CTL fetuses (P = 0.11). A numerical increase in the total number of Pax7+ myoblasts was also observed in fetuses from 25OHD3-supplemented gilts (P = 0.12). Myoblasts derived from the muscles of fetuses from 25OHD3-fed dams displayed an extended proliferative phase in culture compared with those from fetuses of dams fed only D3 (P < 0.0001). The combination of additional muscle fibers and Pax7+ myoblasts with prolonged proliferative capacity could enhance the postnatal skeletal muscle growth potential of fetuses from 25OHD3-supplemented gilts. These data highlight the importance of maternal vitamin D status on the development of fetal skeletal muscle.

Effect of two microbial phytases on mineral availability and retention and bone mineral density in low-phosphorus diets for broilers.

1. The efficacy of supplementation of a low-phosphorus (low-P) maize-soyabean meal diet for broiler chickens with two different microbial (fungal and bacterial) phytases was examined. 2. Broiler chickens received a low-P maize-soyabean meal diet containing either no phytase or one of the two phytases included at one and two times the manufacturer's recommended inclusion level for 21 d. 3. Titanium dioxide was included in the diets as an indigestible marker. Excreta were collected quantitatively from d 18 to 21, and at the end of the study the birds were killed and ileal digesta and leg bone samples collected. 4. No differences were observed for body weight gain and feed intake or apparent metabolisable energy (AME) among all dietary treatment groups. 5. Dietary phytase supplementation improved the apparent retention of Ca, Na and Cu and ileal phytate P absorption from 32% to 44% across inclusion levels. 6. Bone mineral density (BMD) was improved for both phytases across inclusion levels by, on average, 9% for the tibia and 13% for the femur. 7. Dietary phytase supplementation of the low-P diet improved apparent ileal digestibility of serine, glycine, valine, isoleucine, tyrosine, histidine, lysine and arginine. 8. When the results from the present study were combined with the results from other similar published studies and analysed statistically, factors such as dietary P and Ca concentration, as well as bird breed and age, rather than the type or activity of microbial phytase, had the greatest impact on the extent to which dietary supplementation improved P and Ca retention. 9. More work is required to explain the interrelationships between the multiple factors influencing the efficacy of phytase on the availability of dietary minerals.

Feeding 25-hydroxycholecalciferol improves gilt reproductive performance and fetal vitamin D status.

Little information is available regarding the effects of vitamin D and its metabolites on reproduction in swine. To investigate the effects of feeding the circulating metabolite of vitamin D, 25-hydroxycholecalciferol (25OHD3, ROVIMIX Hy • D, DSM Nutritional Products, Basel, Switzerland) on maternal and fetal circulating 25OHD3 concentration and gilt reproductive performance, a total of 40 PIC Camborough-22 gilts (BW on d -6 = 138 kg) in 4 replicates were randomly assigned to 1 of 2 corn-soybean meal-based diets. The control diet (CTL) was formulated to contain 2,500 IU D3/kg diet, and the experimental diet (25OHD3) was formulated to contain 500 IU D3/kg diet + 50 µg 25OHD3/kg diet. Gilts were fed 2.7 kg of their assigned diet once daily beginning 43 d before breeding. Gilt BW were measured on gestational d -6 and d 90. Gilts were artificially inseminated with PIC 337-G semen 12 h and 24 h after showing signs of estrus. Blood samples were collected from the jugular vein on gestational d -43, -13, 46, and 89 for analysis of circulating 25OHD3 plasma concentration and overall vitamin D status of the gilts. At gestational d 90 ± 1, gilts were harvested and reproductive tracts were removed. Fetal weight, sex, crown-to-rump length (CRL), as well as the number of mummified fetuses were recorded. As expected, circulating plasma concentrations of 25OHD3 were not different among treatment groups at d -43 (CTL = 53.8 ng/mL, 25OHD3 = 57.4 ng/mL; P = 0.66). However, gilts fed 25OHD3 had greater (P < 0.001) circulating plasma concentrations of 25OHD3 on d -13 (89.7 vs. 56.7 ng/mL), d 46 (95.8 vs. 55.7 ng/mL), and d 89 (92.8 vs. 58.2 ng/mL) of gestation compared with CTL-fed gilts. Circulating 25OHD3 was also greater in fetuses from 25OHD3-fed gilts on d 90 (P < 0.001). A 23% increase in pregnancy rate was observed in 25OHD3-fed gilts compared with CTL (78% vs. 55%, respectively; P = 0.21). Maternal BW gain (without conceptus), number of mummified fetuses, mean fetal weight, and mean fetal CRL were similar among treatments (P > 0.05). However, litter size was larger (CTL = 10.2; 25OHD3 = 12.7; P = 0.04) in 25OHD3-fed gilts compared with CTL-fed gilts. Notably, mean fetal weight was not decreased in 25OHD3-fed gilts as frequently occurs when litter size is increased. Overall, feeding 25OHD3 to first-service gilts before and during gestation improved both maternal and fetal vitamin D status and improved maternal reproductive performance.

Effect of a novel phytase on growth performance, apparent metabolizable energy, and the availability of minerals and amino acids in a low-phosphorus corn-soybean meal diet for broilers.

The addition of microbial phytase to diets for broiler chickens has been shown to improve the availability of phytate P, total P, some other minerals, and amino acids. In this study, the effect of a novel microbial phytase expressed by synthetic genes in Aspergillus oryzae on amino acid and mineral availability was assessed. Phytase was incorporated (1,000 and 2,000 U/kg) into low-P corn-soybean meal-based diets for broilers. Broilers received the experimental diets for 3 wk, and excreta were collected from d 18 to 21 for the determination of AME and mineral retention. On the 22nd day, the broilers were killed and the left leg removed and ileal digesta collected. Ileal phytate P and total P absorption, ileal amino acid digestibility, as well as the bone mineral content and bone mineral density were determined. Ileal phytate P absorption and absorbed phytate P content of the low-P corn-soybean meal diet were significantly (P < 0.05) higher after dietary inclusion of the novel phytase (49-60% and 65-77% higher, respectively). Apparent ileal total P absorption and apparent total P retention was 12 to 16% and 14 to 19% higher (P < 0.05), respectively, after dietary inclusion of phytase. The bone mineral content and bone mineral density in the tibia were 32 to 35% and 19 to 21% higher (P < 0.05), respectively, after dietary phytase inclusion. The apparent ileal digestibility of threonine, tyrosine, and histidine increased significantly (P < 0.05) by 14, 9, and 7%, respectively, after dietary inclusion of microbial phytase. Overall, the inclusion of a novel microbial phytase into a low-P corn-soybean meal diet for broiler chickens greatly increased phytate P and total P absorption, bone mineral content and density, as well as the digestibility of some amino acids.

Dysregulation of microRNA-204 mediates migration and invasion of endometrial cancer by regulating FOXC1.

MicroRNAs (miRNAs) regulate mRNA stability and protein expression, and certain miRNAs have been demonstrated to act either as oncogenes or tumor suppressors. Differential miRNA expression signatures have been documented in many human cancers but the role of miRNAs in endometrioid endometrial cancer (EEC) remains poorly understood. This study identifies significantly dysregulated miRNAs of EEC cells, and characterizes their impact on the malignant phenotype. We studied the expression of 365 human miRNAs using Taqman low density arrays in EECs and normal endometriums. Candidate differentially expressed miRNAs were validated by quantitative real-time PCR. Expression of highly dysregulated miRNAs was examined in vitro through the effect of anti-/pre-miRNA transfection on the malignant phenotype. We identified 16 significantly dysregulated miRNAs in EEC and 7 of these are novel findings with respect to EEC. Antagonizing the function of miR-7, miR-194 and miR-449b, or overexpressing miR-204, repressed migration, invasion and extracellular matrix-adhesion in HEC1A endometrial cancer cells. FOXC1 was determined as a target gene of miR-204, and two binding sites in the 3'-untranslated region were validated by dual luciferase reporter assay. FOXC1 expression was inversely related to miR-204 expression in EEC. Functional analysis revealed the involvement of FOXC1 in migration and invasion of HEC1A cells. Our results present dysfunctional miRNAs in endometrial cancer and identify a crucial role for miR-204-FOXC1 interaction in endometrial cancer progression. This miRNA signature offers a potential biomarker for predicting EEC outcomes, and targeting of these cancer progression- and metastasis-related miRNAs offers a novel potential therapeutic strategy for the disease.