Factors determining the persistence of prenatal stress urinary incontinence 12 months postpartum.

OBJECTIVE: Whilst many studies have explored the mechanisms of stress urinary incontinence (SUI) following various modes of delivery, few have examined outcomes of postpartum SUI in women who experienced new-onset SUI during their pregnancy. Our primary objective was to investigate the risk factors for persistent postpartum SUI in women with new-onset SUI during pregnancy at 1-year follow-up following vaginal delivery. MATERIALS AND METHODS: 303 women with new-onset SUI during pregnancy who underwent vaginal delivery in a university hospital between 2014 and 2015 were included. In-person interviews were conducted for all participants on the second postpartum day, followed by phone interviews at 12 months postpartum, with completion of structured questionnaires, including Urogenital Distress Inventory Short Form (UDI-6) and Incontinence Impact Questionnaire Short Form (IIQ-7). Demographic, obstetrics and questionnaire scores were analyzed and compared between the group of women who experienced persistent postpartum SUI and the group who did not. RESULTS: At 12 months postpartum, 16.5% (n = 50) of women had persistent postpartum SUI, with 83.5% (n = 253) experiencing resolution of SUI symptoms. Maternal age ≥35 years (aOR = 2.62; 95% CI, 1.40-4.87, P = 0.002), gestational age at birth ≥40 weeks (aOR = 2.21; 95% CI, 1.12-4.37, P = 0.022), and severe perineal lacerations (aOR = 2.32; 95% CI, 1.27-4.45, P = 0.013) were independent risk factors for persistent postpartum SUI for women following vaginal delivery at 1-year follow-up. CONCLUSION: The prevalence of persistent postpartum SUI at 1-year following vaginal delivery is 16.5%, with advanced maternal age, gestational age at birth ≥40 weeks and severe perineal lacerations being independent risk factors.

Impact of intrinsic sphincter deficiency on mid-urethral sling outcomes.

INTRODUCTION AND HYPOTHESIS: Our primary objective was to study outcomes of patients with intrinsic sphincter deficiency (ISD) following mid-urethral slings (MUS) at 1-year. Our secondary objective was to delineate factors affecting success in these patients. METHODS: Six hundred eighty-eight patients who had MUS between January 2004 and April 2017 were reviewed retrospectively; 48 women were preoperatively diagnosed with ISD. All completed urodynamic studies and validated quality-of-life (QOL) questionnaires at baseline and 1 year. Primary outcomes were objective and subjective cure of stress incontinence, defined as no involuntary urine leakage during filling cystometry and 1-h pad test < 2 g and negative response to Urogenital Distress Inventory-6 Question 3. Ultrasound was performed to determine tape position, urethral mobility and kinking at 1 year. RESULTS: Women with ISD had significantly lower objective and subjective cure rates of 52.1% and 47.9%, respectively, compared to an overall of 88.2% and 85.9%. QOL scores significantly improved in those with successful surgeries. The sling type did not make a difference. Multivariate logistic regression identified reduced urethral mobility [OR 2.11 (1.24-3.75)], lower maximum urethral closure pressure (MUCP) [OR 1.61 (1.05-3.41)] and tape position [OR 3.12 (1.41-8.71)] to be associated with higher odds of failed slings for women with ISD. CONCLUSIONS: Although there are good overall success in women undergoing MUS, those with ISD have significantly lower cure rates at 1 year. Factors related to failure include reduced urethral mobility, low MUCP and relative tape position further away from the bladder neck. Optimal management of patients with ISD and reduced urethral mobility remains challenging.

Ultrasonography and clinical outcomes following anti-incontinence procedures (Solyx™ tape): a 3-year post-operative review.

INTRODUCTION AND HYPOTHESIS: Our primary objective was to study objective and subjective outcomes of patients with urodynamic stress incontinence (USI) following Solyx™ at 3-year follow-up. Our secondary objective was to evaluate ultrasonographic tape and bladder neck position and mobility. METHODS: Records of 88 women who received Solyx™ surgery between September 2015 and December 2017 were reviewed. Ultrasonographic sling evaluation was performed at 6 months and 3 years postoperatively. Primary outcomes were objective and subjective cure of stress incontinence, defined as no involuntary urine leakage during filling cystometry, 1-h pad test < 2 g and negative response to Urogenital Distress Inventory-6 Question 3. RESULTS: Subjective and objective cure rates at 3 years were 85.2% and 87.5%, respectively, with no complications reported. QOL improvements were maintained. Bladder neck position and mobility had no significant change between 6-month and 3-year follow-up. Tape position demonstrated significant shifts in the y-axis at both rest and Valsalva and in the x-axis at Valsalva between 6 months and 3 years; overall mobility was unchanged. Percentile of sling location remained unchanged at 60.1%, as did percentage of urethral kinking (67.9%) achieved. Risk factors for failure were bladder neck hypomobility postoperatively and no urethral kinking postoperatively. CONCLUSIONS: There was good sustained objective and subjective cure with improved QOL in women who underwent Solyx™ for USI at 3-year follow-up. Ultrasonographic evaluation showed a tape position shift upwards and backwards with unchanged tape and bladder neck mobility. Percentile of sling location and rates of dynamic kinking were maintained.

De novo detrusor overactivity and urgency after mid-urethral slings for urodynamic stress incontinence.

INTRODUCTION AND HYPOTHESIS: The objective was to identify incidence and risk factors of de novo urgency and detrusor overactivity (DO) following mid-urethral slings (MUS) in patients with urodynamic stress incontinence (USI) without urgency. METHODS: A total of 688 women between January 2004 and July 2017 were reviewed retrospectively. De novo urgency was established with a positive response to question 2 on the Urogenital Distress Inventory-6 questionnaire (UDI-6). Objective cure of USI is no involuntary urine leakage during filling cystometry and pad test < 2 g. Subjective cure of stress urinary incontinence (SUI) is defined as a negative response to question 3 on UDI-6. Multivariate logistic regression was used to identify risk factors for failure. RESULTS: Forty-four out of 688 women (6.4%) developed de novo urgency, with 16 out of 688 (2.3%) demonstrating de novo DO. Subjective cure for women with de novo urgency was significantly lower at 35 out of 44 (79.5%) compared with 556 out of 644 (86.3%) in those with no urgency (p < 0.001). Objective cure for women with de novo DO was significantly lower at 8 out of 16 (50%) compared with 599 out of 672 (89.1%) in those with detrusor stability (p < 0.001). Quality of life improved for all. Age ≥ 66 (OR, 1.23; 1.07), increased bladder sensation (OR, 4.18; 3.80), lower bladder capacity (OR, 5.28; 4.97), lower maximum urethral closure pressure (OR, 2.32; 5.20), and pad test > 100 g (OR, 1.08; 1.15) were independent risk factors for de novo urgency and DO. Diabetes (OR, 1.32) was an independent predictor of de novo urgency. CONCLUSION: Cure is significantly reduced in women who report symptoms of de novo urgency or demonstrate DO after MUS at 1 year. Independent risk factors include age ≥ 66, increased bladder sensation, lower bladder capacity, lower maximum urethral closure pressure, greater pad loss, and diabetes.

Anterior-Apical Transvaginal Mesh (Surelift) for Advanced Urogenital Prolapse: Surgical and Functional Outcomes at 1 Year.

STUDY OBJECTIVE: To determine the objective and subjective outcomes of pelvic organ prolapse (POP) surgery using a modified Surelift system (Neomedic International, Barcelona, Spain) and to evaluate surgical complications and postoperative impact on quality of life (QOL) and lower urinary tract symptoms. DESIGN: Retrospective cohort study. SETTING: Tertiary-care university hospital. PATIENTS: Patients with symptomatic anterior or apical POP stage III and above. INTERVENTIONS: All patients underwent pelvic reconstructive surgery with a modified Surelift transvaginal mesh kit. MEASUREMENTS AND MAIN RESULTS: Eighty-three women who underwent pelvic reconstructive surgery with a modified Surelift for symptomatic anterior or apical prolapse stage III and above from April 2018 to January 2019 were reviewed retrospectively. All completed a 72-hour voiding diary, urodynamic study, and multiple validated QOL questionnaires at baseline and at between 6 and 12 months postoperatively. Descriptive statistics were used for demographics and perioperative data. Paired-samples t test and the McNemar test were applied for comparison of pre- and postoperative continuous and categoric data, respectively. The primary outcomes were the objective cure of POP, defined as anterior and apical prolapse Pelvic Organ Prolapse Quantification System ≤ stage I, and subjective cure on the basis of negative answers to Pelvic Organ Prolapse Distress Inventory 6. The objective and subjective cure rates at 1 year were 97.6% and 92.8%, respectively. There were significant improvements in QOL scores postoperatively. Although bladder outlet obstruction improved, de novo urodynamic stress incontinence and stress urinary incontinence were increased at 18.9% and 21.6%, respectively, at 1-year follow-up. The mesh extrusion rate was 4.8%. CONCLUSION: A modified Surelift has good objective and subjective cure rates at 1 year postoperatively with 4.8% mesh extrusion rate. There was significant improvement in lower urinary tract symptoms and QOL. De novo urodynamic stress incontinence at 6 months to 12 months was increased, but it was not sufficiently bothersome to warrant surgery.

Immunochemical analysis on polypropylene mesh: does mesh size make a difference?

INTRODUCTION AND HYPOTHESIS: The aim of the study is to demonstrate the impact of the size of implanted mesh in relation to its immunohistochemical reaction implanted into animal models. METHODS: An experimental study utilizing 54 female Sprague Dawley (SD) rats was divided into five groups: control, sham, and study groups (mesh-small [M-S], mesh-medium [M-M], mesh-large [M-L]). The M-S group used a mesh size of 0.2 × 0.2 cm, the M-M group a mesh size of 0.5 × 0.5 cm, and the M-L a mesh size of 0.7 × 1.0 cm. The sham group underwent vaginal dissection with no mesh implantation. The rats were sacrificed using isoflurane overdose on days 7 and 30. The mesh with the surrounding vaginal and bladder wall tissues were removed and processed for histochemical and western blot analysis. RESULTS: There is a significant increase in IL-1 and TNF-α immunoreactivity in the M-M and M-L groups on day 7 when compared with the sham group with p values of 0.001 and < 0.001 respectively. M-L showed significantly higher immunoreactivity to TNF-α persisting until day 30. All study groups presented a significantly higher immunoreactivity to MMP-2 and NGF on day 7. However, reactivity to NGF does not persist to day 30 in all groups. Immunoreactivity to CD 31 on days 7 and 30 appears significantly greater in the M-M and M-L groups, with the reaction in the M-L group continuing until day 30. CONCLUSION: Mesh size is directly proportional to the inflammatory reaction in the host tissue. The prolonged inflammatory process leads to delayed tissue remodeling and angiogenesis, which could delay mesh-tissue integration.

Mid Urethral Slings for the Treatment of Urodynamic Stress Incontinence in Overweight and Obese Women: Surgical Outcomes and Preoperative Predictors of Failure.

PURPOSE: We evaluated mid urethral sling outcomes in overweight and obese patients compared to normal weight patients and identified risk factors for failure in this population. MATERIALS AND METHODS: Records of 688 women between January 2004 and July 2017 were retrospectively reviewed. Patients received urodynamic studies, 1-hour pad test, Urogenital Distress Inventory-6 and Incontinence Impact Questionnaire-7, and were divided into normal weight, overweight and obese. Objective cure at 1 year was defined as no involuntary urine leakage during filling cystometry and pad test less than 2 gm. Subjective cure was established by negative response to question 3 on Urogenital Distress Inventory-6. McNemar's test, chi-square test, Mann-Whitney U and Fisher's exact test were used for paired categorical variables. Independent samples t-tests and paired t-test were used for continuous parametric variables. Multivariate logistic regression was used to identify risk factors for failure. RESULTS: Objective and subjective cure in normal, overweight and obese patients was 91.4% and 89.1%, 87.5% and 86%, and 76% and 70.1%, respectively. There was no difference in surgical complications. Obese patients had worse quality of life scores preoperatively and postoperatively. Risk factors in obese patients with failed mid urethral sling included 66 years old or older (OR 2.02, 1.56-3.98), menopause (OR 4.21, 1.21-14.22), previous prolapse surgery (OR 4.57, 2.36-8.52), diabetes (OR 2.79, 1.61-5.99) and intrinsic sphincter deficiency (OR 5.06, 3.08-9.64). CONCLUSIONS: Obese women with mid urethral sling had lower objective and subjective cure at 1 year and worse quality of life scores compared to normal and overweight women. Risk factors for failure include age, diabetes, menopause, previous prolapse surgery and intrinsic sphincter deficiency.

Risk factors and prevalence of urinary incontinence in mid-life Singaporean women: the Integrated Women's Health Program.

INTRODUCTION AND HYPOTHESIS: The objective was to identify the prevalence and risk factors for urinary incontinence (UI) in healthy midlife Singaporean women. METHODS: Healthy women, aged 45-69 years, were assessed for UI and sociodemographic characteristics, including ethnicity, menopausal status, parity, and body mass index (BMI). UI subtypes corresponding to stress (SUI) alone, urge (UUI) alone, mixed (MUI), and leakage (drops only) incontinence were classified using the Urinary Distress Inventory 6 (UDI-6). Risk factors were examined using Chi-squared tests, followed by sequential multivariate logistic regression to estimate adjusted odds ratios (aOR and 95% confidence intervals). RESULTS: A total of 1,119 women (mean age 56.2 ± 5.2) completed the UDI-6. 52.3% reported any UI; MUI and SUI were the most common, each affecting 20% of women. Post-menopausal women had a lower risk (aOR 0.5 [0.3-0.9]) of SUI, but a higher risk (aOR 4.4 [1.0-19.9]) of UUI compared with premenopausal women. Higher education was negatively associated (aOR 0.3 [0.2-0.7]) with UUI, but positively associated with MUI (aOR 2.3 [1.3-4.0]). Parity (1-2 children) increased the risk of SUI (aOR 1.8 [1.0-3.1]), but reduced the risk of UUI (aOR 0.4 [0.2-0.9]). Obesity was associated with increased risk for MUI (aOR 2.2 [1.4-3.4]) and leakage (aOR 2.0 [1.0-4.1]). Malays and Indians had a higher risk of MUI, having (aOR 2.1 (1.2-3.7) and 1.7 (1.1-2.7) respectively compared with Chinese, a difference mediated by higher BMI. CONCLUSION: Urinary incontinence is a major morbidity prevalent in healthy midlife Asian women. Post-menopausal status, education level, parity, BMI (and its link with ethnicity) are independent risk factors in this population, and should be incorporated into counseling and targeted interventions.

Tubo-Ovarian Abscesses: Epidemiology and Predictors for Failed Response to Medical Management in an Asian Population.

Pelvic inflammatory disease (PID) complicated by tubo-ovarian abscesses (TOA) has long-term sequelae in women of reproductive age. Consensus on the optimal treatment of TOA remains lacking. Most clinicians utilize antibiotics as a first-line conservative approach, failing which invasive intervention is adopted. Our aim is to identify risk factors predicting failed response to conservative medical management for TOA in an Asian population. A retrospective cohort study of 136 patients admitted to a tertiary hospital in Singapore for TOA between July 2013 and December 2017 was performed. Patients were classified into 2 groups: successful medical treatment with intravenous antibiotics and failed medical treatment requiring invasive intervention. 111 (81.6%) of patients were successfully treated with conservative medical approach using intravenous antibiotics; 25 (18.4%) required invasive intervention having failed medical therapy. Multivariate logistic regression model adjusted for age, ethnicity, C-reactive Protein (CRP), TOA size, and body mass index (BMI) showed the odds ratio (OR) of each centimetre increase in TOA size to be 1.28 (95% confidence interval (CI) 1.03-1.61; P=0.030) and every kg/m2 increase in BMI to be 1.10 (95% CI 1.00-1.21; P=0.040). Failed medical management was predicted by a cutoff of TOA size ≥ 7.4 cm and ≥ BMI 24.9 kg/m2. Patients who failed medical treatment received a mean of 4.0±2.1 days of antibiotics before a decision for invasive intervention was made, with a significantly longer intravenous antibiotic duration (9.4±4.3 versus 3.6±2.2 days; P <0.001) and prolonged hospitalization (10.8± 3.6 versus 4.5 ± 2.0 days; P <0.001) compared to the medical group. Patients with higher BMI and larger TOA size were associated with failed response to conservative medical management in our study population. Early identification of these patients for failed medical therapy is imperative for timely invasive intervention to avoid prolonged hospitalization, antibiotic usage, and patient morbidity.

Gestational Diabetes Alters Functions in Offspring's Umbilical Cord Cells With Implications for Cardiovascular Health.

Because noncommunicable diseases such as type 2 diabetes mellitus have their roots in prenatal development and conditions such as maternal gestational diabetes mellitus (GDM), we aimed to test this hypothesis in primary cells derived from the offspring of mothers with GDM compared with control subjects. We have assessed primary umbilical cord-derived cells such as human umbilical vein endothelial cells (HUVECs) and Wharton's jelly-derived mesenchymal stem cells from the offspring of mothers with and without GDM. We have compared the primary isolates in cell-based assays measuring proliferation, mitochondrial oxygen consumption, and the ability to support blood vessel growth. We conducted gene expression microarray studies with subsequent pathway analysis and candidate gene validation. We observed striking differences between the two groups, such as lower metabolic rates and impairment of endothelial tube formation in cells with GDM background. HUVECs from subjects with maternal GDM have lower expression of the antiapoptotic protein BCL-xL, suggesting compromised angiogenic capabilities. Comparative gene expression analysis revealed blood vessel formation as a major pathway enriched in the GDM-derived HUVECs with the surface marker CD44 as a gene underexpressed in the GDM group. Functional validation of CD44 revealed that it regulates tube formation in HUVECs, thereby providing insights into a pathway imprinted in primary umbilical cord-derived cells from GDM offspring. Our data demonstrate that primary cells isolated from the umbilical cord of offspring born to mothers with GDM maintain metabolic and molecular imprints of maternal hyperglycemia, reflecting an increased risk for cardiovascular disease later in life.

E2F1 Orchestrates Transcriptomics and Oxidative Metabolism in Wharton's Jelly-Derived Mesenchymal Stem Cells from Growth-Restricted Infants.

Wharton's jelly-derived Mesenchymal Stem Cells (MSCs) isolated from newborns with intrauterine fetal growth restriction were previously shown to exert anabolic features including insulin hypersensitivity. Here, we extend these observations and demonstrate that MSCs from small for gestational age (SGA) individuals have decreased mitochondrial oxygen consumption rates. Comparing normally grown and SGA MSCs using next generation sequencing studies, we measured global transcriptomic and epigenetic profiles and identified E2F1 as an over-expressed transcription factor regulating oxidative metabolism in the SGA group. We further show that E2F1 regulates the differential transcriptome found in SGA derived MSCs and is associated with the activating histone marks H3K27ac and H3K4me3. One of the key genes regulated by E2F1 was found to be the fatty acid elongase ELOVL2, a gene involved in the endogenous synthesis of docosahexaenoic acid (DHA). Finally, we shed light on how the E2F1-ELOVL2 pathway may alter oxidative respiration in the SGA condition by contributing to the maintenance of cellular metabolic homeostasis.

The transcription factor SOX6 contributes to the developmental origins of obesity by promoting adipogenesis.

An association between impaired fetal growth and the postnatal development of obesity has been established. Here, by comparing adipocytes differentiated from mesenchymal stem cells (MSCs) taken from the umbilical cord and derived from normal and growth-restricted neonates, we identified the transcription factor SOX6 as highly expressed only in growth-restricted individuals. We found that SOX6 regulates adipogenesis in vertebrate species by activating adipogenic regulators including PPARγ, C/EBPα and MEST. We further show that SOX6 interacts with ß-catenin in adipocytes, suggesting an inhibition of WNT/ß-catenin signaling, thereby promoting adipogenesis. The upstream regulatory region of the MEST gene in MSCs from growth-restricted subjects harbors hypomethylated CpGs next to SOX6 binding motifs, and we found that SOX6 binding is impaired by adjacent CpG methylation. In summary, we report that SOX6 is a novel regulator of adipogenesis synergizing with epigenetic mechanisms.

ACSL1 Is Associated With Fetal Programming of Insulin Sensitivity and Cellular Lipid Content.

Individuals who are born small for gestational age (SGA) have a risk to develop various metabolic diseases during their life course. The biological memory of the prenatal state of growth restricted individuals may be reflected in epigenetic alterations in stem cell populations. Mesenchymal stem cells (MSCs) from the Wharton's jelly of umbilical cord tissue are multipotent, and we generated primary umbilical cord MSC isolates from SGA and normal neonates, which were subsequently differentiated into adipocytes. We established chromatin state maps for histone marks H3K27 acetylation and H3K27 trimethylation and tested whether enrichment of these marks was associated with gene expression changes. After validating gene expression levels for 10 significant chromatin immunoprecipitation sequencing candidate genes, we selected acyl-coenzyme A synthetase 1 (ACSL1) for further investigations due to its key roles in lipid metabolism. The ACSL1 gene was found to be highly associated with histone acetylation in adipocytes differentiated from MSCs with SGA background. In SGA-derived adipocytes, the ACSL1 expression level was also found to be associated with increased lipid loading as well as higher insulin sensitivity. ACSL1 depletion led to changes in expression of candidate genes such as proinflammatory chemokines and down-regulated both, the amount of cellular lipids and glucose uptake. Increased ACSL1, as well as modulated downstream candidate gene expression, may reflect the obese state, as detected in mice fed a high-fat diet. In summary, we believe that ACSL1 is a programmable mediator of insulin sensitivity and cellular lipid content and adipocytes differentiated from Wharton's jelly MSCs recapitulate important physiological characteristics of SGA individuals.

Ureterovaginal fistula after insertion of a McDonald suture: Case report and review of published reports.

Complications associated with cerclage that are commonly described in the existing published reports include injuries to the cervix or bladder, premature rupture of membranes, chorioamnionitis and bleeding. We report an unusual complication of a ureterovaginal fistula formation after the insertion of a McDonald suture.

Factors associated with dental caries among selected urban school children in Kuala Lumpur, Malaysia

This study aimed to assess the nutritional status (BMI), oral health behaviour, sugar consumption and the associated factors with dental caries among a group of 7 to 11 years old children in Kuala Lumpur, Malaysia. Three hundred and twelve students were recruited from February to July 2013. Information gathered were their socio-demographic characteristics, body mass index, sugar consumption, oral-health behaviour, oral hygiene index and decay-missing-filled teeth (dmft) index. Anthropometry measurements and sugar intake was measured using verified tools. Meanwhile, dmft was examined using the World Health Organization (WHO) criteria. 53.7% of the children were of the normal body weight with mean sugar consumption of 31.81±4.24 g/day. Prevalence of dental caries was reported at 44.6% (95% CI: 42.2, 53.3) with a mean (SD) dmft of 1.27(1.84). No association was found between dental caries and weight status distribution. Most children tend to brush their teeth 2 times or more in a day (75%), however, they spent lesser time in tooth brushing (5.4%) and do not practice flossing (78%). Regression analysis showed that age (p<0.001), duration of teeth brushing (p=0.023) and the oral hygiene index (p=0.002) were significant predictors of dental caries among this group of children. Present findings suggest that younger children, longer time taken to brush teeth and poorer oral hygiene index were predisposing factors in dental caries, especially for young children. Hence, education on dental health is important to improve oral health behaviour and oral hygiene practices to further reduce dental caries incidences among young children.

Molecular pathways reflecting poor intrauterine growth are found in Wharton's jelly-derived mesenchymal stem cells.

STUDY QUESTION: Are molecular pathways reflecting the biology of small for gestational age (SGA) neonates preserved in umbilical cord-derived mesenchymal stem cells (MSCs)? SUMMARY ANSWER: MSCs from SGA newborns were found to express an altered EGR-1-dependent gene network involved in the regulation of cell proliferation and oxidative stress. WHAT IS KNOWN ALREADY: Individuals with suboptimal intrauterine development are at greater risk of metabolic diseases such as type II diabetes, obesity and cardiovascular disease. STUDY DESIGN, SIZE, DURATION: Umbilical cords (n = 283) from the GUSTO (growing up in Singapore towards healthy outcomes) birth cohort study, and primary MSC isolates established from SGA and matched control cases (n = 6 per group), were subjected to gene expression analysis and candidate genes were studied for functional validation. PARTICIPANTS/MATERIALS, SETTING, METHODS: Umbilical cord specimens were derived from babies born at the National University Hospital (NUH) in Singapore. Local ethical approval was obtained. MSC isolates were established in Wharton's jelly and molecular analysis was conducted by gene expression microarrays and RT-PCR. Cells from SGA and control groups were compared in the presence and absence of insulin and candidate gene function was studied via siRNA-mediated gene knockdown and over-expression experiments in MSCs. MAIN RESULTS AND THE ROLE OF CHANCE: Using repeated measure ANOVAs, proliferation rates of MSCs isolated from SGA neonates were found to be significantly increased (P < 0.01). In the absence of insulin, EGR-1 levels were found to be significantly reduced in the group of SGA-derived MSCs, whereas EGR-1 expression was found to be up-regulated in the same group in the presence of insulin (P < 0.01). EGR-1 was found to induce expression of COX-2 in the SGA group (P < 0.01) and both, EGR-1 and COX-2 stimulated glucose uptake in MSCs (P < 0.01). EGR-1 and COX-2 levels were associated in whole umbilical cords (n = 283, P < 0.01) and EGR-1 positively correlated with abdominal circumference and birthweight (n = 91, P < 0.01 and n = 91, P < 0.01). LIMITATIONS, REASONS FOR CAUTION: Cell models may not entirely reflect the physiology of the host and patient follow-up studies will be necessary for further clinical validation. WIDER IMPLICATIONS OF THE FINDINGS: Our study suggests that Wharton's jelly-derived MSCs are useful in identifying pathways specific for fetal growth restriction. STUDY FUNDING/COMPETING INTERESTS: This work is supported by the Translational Clinical Research (TCR) Flagship Program on Developmental Pathways to Metabolic Disease funded by the National Research Foundation (NRF) and administered by the National Medical Research Council (NMRC), Singapore- NMRC/TCR/004-NUS/2008'. SICS Investigators are supported through the Agency for Science Technology and Research (A*STAR) funding. No potential conflicts of interest relevant to this article were reported.

Surgical pitfalls in patients with Ehlers-Danlos type IV: a case of spontaneous sigmoid perforation in a 17-year-old male.

Ehlers-Danlos syndrome (EDS) is a group of well described connective tissue disorders in which collagen production is impaired. The surgical management of affected individuals remains challenging, with no general consensus. We report a case of spontaneous sigmoid perforation in a 17-year-old Eurasian male, in whom we subsequently established the diagnosis of EDS type IV (EDS-IV). We review the literature to discuss the clinical features and diagnosis, and the recommended therapeutic management.