noor azmi mat adenan | University of Malaya, Malaysia (original) (raw)
Papers by noor azmi mat adenan
Biomedical Imaging and Intervention Journal, 2010
Background: Transcatheter uterine artery embolisation (UAE) for the treatment of symptomatic fibr... more Background: Transcatheter uterine artery embolisation (UAE) for the treatment of symptomatic fibroids has been performed in several centres in the United States, Western Europe and Asia with promising results. This study reports the authors' experience with UAE at the University Malaya Medical Centre. Method: Fifty women with symptomatic uterine fibroids who declined surgery were treated by transcatheter UAE. The uterine arteries were selectively catheterised and embolised with polyvinyl alcohol particles. Post-procedure analgesia was administered via patientcontrolled analgesic pump. The patients were followed up at an interval of 6/12 clinically and with MRI. Results: Transcatheter UAE was performed on all 50 patients with no major complications. 49 patients had both uterine arteries embolised while 1 patient had only the right uterine artery embolised on account of hypoplasia of the left uterine artery due to previous myomectomy. The mean hospital stay was 3.5 days (range, 2 to 7). At a mean follow-up of 24/52, all patients reported improvements in their presenting symptoms. Objective improvement in terms of reduction of uterine and fibroid sizes was determined on MRI. One patient, who initially responded with a decrease in uterine and dominant fibroid size, became symptomatic (menorrhagia) after 6 months and subsequent endometrial sampling revealed cystic glandular hyperplasia for which total abdominal hysterectomy was performed. Two other patients had no change in symptoms and after hysterectomy, the pathology revealed concurrent adenomyosis. Another 2 patients with cervical fibroids were treated with hysterectomy as there was no gross reduction in the size of fibroid following UAE. Overall, 90% of the patients had dramatic improvement of anaemia and symptoms at 1 year follow-up. Conclusion: Out of the 50 patients, 17 patients had total disappearance of their fibroids and 28 patients had more than 50% reduction in the size of fibroids after 1 year. 5 patients ended up with total abdominal hysterectomy. These results suggest that UAE is an appealing alternative to hysterectomy or myomectomy for many women with symptomatic fibroids.
Journal of Health and Translational Medicine
To see the trend in managing singleton breech pregnancy after the term breech trial. Secondly to ... more To see the trend in managing singleton breech pregnancy after the term breech trial. Secondly to compare the safety of different modes of delivery for term, singleton breeches by looking at the immediate neonatal outcome, based on our own experience. Breech infants were identified by examining computer-stored maternal discharge records of hospitalization for the years 1990 and 2000 respectively. Parameters studied included planned mode of delivery, actual mode of delivery, parity, previous vaginal delivery, Apgar score at five minute, birth weight, referral to special care nursery and neonatal morbidity. Of 6,496 deliveries in 1990 and 5,081 in 2000, there were 220 (3.4%) and 148 (2.9%) term breech infants respectively, of which 115 (for 1990) and 102 (for 2000) case records were available. In 1990, 62.6% of the women had trial of vaginal breech delivery but only 24.5% of the women in 2000 were allowed to do so (p < 0.05). Caesarean section rate for singleton breeches increased from 51.3% in 1990 to 84.3% in 2000 (p < 0.05). Mean Apgar score at five minutes was significantly lower after vaginal breech delivery (9.40 ± 1.36) compared to after Caesarean section (9.72 ± 0.712) but there was no clinical significance. There was a noticeable trend towards Caesarean section and less trial of vaginal delivery. Neonatal outcomes of babies born abdominally were statistically better than those born vaginally but there was little clinical impact. Perhaps in properly selected cases, a planned vaginal breech delivery still has a role to play.
Nature Communications, Mar 2013
HNF1B is overexpressed in clear cell epithelial ovarian cancer, and we observed epigenetic silenc... more HNF1B is overexpressed in clear cell epithelial ovarian cancer, and we observed epigenetic silencing in serous epithelial ovarian cancer, leading us to hypothesize that variation in this gene differentially associates with epithelial ovarian cancer risk according to histological subtype. Here we comprehensively map variation in HNF1B with respect to epithelial ovarian cancer risk and analyse DNA methylation and expression profiles across histological subtypes. Different single-nucleotide polymorphisms associate with invasive serous (rs7405776 odds ratio (OR) = 1.13, P = 3.1 x 10(-10)) and clear cell (rs11651755 OR = 0.77, P = 1.6 x 10(-8)) epithelial ovarian cancer. Risk alleles for the serous subtype associate with higher HNF1B-promoter methylation in these tumours. Unmethylated, expressed HNF1B, primarily present in clear cell tumours, coincides with a CpG island methylator phenotype affecting numerous other promoters throughout the genome. Different variants in HNF1B associate with risk of serous and clear cell epithelial ovarian cancer; DNA methylation and expression patterns are also notably distinct between these subtypes. These findings underscore distinct mechanisms driving different epithelial ovarian cancer histological subtypes.
Sādhanā
Objective identification of pain due to uterine contraction during the first stage of labour usin... more Objective identification of pain due to uterine contraction during the first stage of labour using continuous EEG signals and SVM. Sadhana-Academy Proceedings in Engineering Sciences, 44(4), Article number: 87 1-12.
Taiwanese journal of obstetrics & gynecology, 2018
To validate the gene expression profile obtained from the previous microarray analysis and to fur... more To validate the gene expression profile obtained from the previous microarray analysis and to further study the biological functions of these genes in endometrial cancer. From our previous study, we identified 621 differentially expressed genes in laser-captured microdissected endometrioid endometrial cancer as compared to normal endometrial cells. Among these genes, 146 were significantly up-regulated in endometrial cancer. A total of 20 genes were selected from the list of up-regulated genes for the validation assay. The qPCR confirmed that 19 out of the 20 genes were up-regulated in endometrial cancer compared with normal endometrium. RNA interference (RNAi) was used to knockdown the expression of the upregulated genes in ECC-1 and HEC-1A endometrial cancer cell lines and its effect on proliferation, migration and invasion were examined. Knockdown of MIF, SOD2, HIF1A and SLC7A5 by RNAi significantly decreased the proliferation of ECC-1 cells (p < 0.05). Our results also showed...
Reproductive biology, Jan 23, 2017
A parallel group superiority prospective randomised controlled trial was devised to compare the c... more A parallel group superiority prospective randomised controlled trial was devised to compare the culture characteristics of human pre-implantation stage embryos during uninterrupted culture in a time lapse incubator (TLI) versus the conventional model of interrupted culture in a standard incubator (SI) under low oxygen tension using a single step medium. 221 patients aged 35-and-under, 124 patients aged between 36 and 39 and 86 patients aged 40-and-over years were randomised and cultured either in a SI or in a TLI. Patients in the three age groups were distributed between the TLI and SI in a 1:1 ratio. The development of embryos on days 2, 3 and 5, and the clinical pregnancy and implantation rates were recorded. The fertilisation rate, development of day 2 and clinical pregnancy rates were similar in both treatments but the 8-cell development rate in all age groups combined (p = 0.016), blastocyst development rate (p = 0.0022) and the implantation rate (p = 0.0022) was significantly ...
Journal of Obstetrics and Gynaecology Research
To evaluate the efficacy of acupressure at the Neiguan point (Pericardium [P]6) as adjuvant treat... more To evaluate the efficacy of acupressure at the Neiguan point (Pericardium [P]6) as adjuvant treatment during inpatient management of severe nausea and vomiting in pregnancy. Low risk, spontaneously conceived singleton pregnancies were randomly assigned to a treatment group, who received an acupressure band placed at the Neiguan point (P6) or a placebo group who received an otherwise identical non-stimulating wristband. Participants wore the band for 12 h daily for the first three days of admission. The primary outcome measure was the severity of symptoms of nausea, vomiting and retching, recorded according to Pregnancy-Unique Quantification of Emesis and Nausea score. There was a statistically significant improvement in Pregnancy-Unique Quantification of Emesis and Nausea scores from day 1 until day 3 of admission in the treatment group compared with the placebo. Patients who received Neiguan point acupressure also showed a significant improvement in their ketonuria scores. The treatment group required a shorter hospital stay compared with the placebo. The only reported side effect of the acupressure band was redness on the wrist. The use of the acupressure band at the Neiguan point (P6) for 12 h daily for three days for inpatients with hyperemesis gravidarum significantly reduced the symptoms of nausea, vomiting and retching and ketonuria and led to a reduction in hospital stay. We recommend the use of the acupressure band at the Neiguan point (P6) as an adjunct/supplementary therapy to co-exist with the standard care of management for hyperemesis gravidarum, particularly in low-risk pregnant women.
Reproductive biology, Jan 19, 2017
There is a paucity of studies on effect of iron in embryo culture procedures. This study aims to ... more There is a paucity of studies on effect of iron in embryo culture procedures. This study aims to ascertain the optimal, tolerance and toxic levels of iron in a protein-free embryo culture medium (PFM) to determine the effect of iron on embryonic development. The application of PFM in assisted reproductive technologies (ART) is intended to eliminate disease transmission and improve ART treatment outcome. The optimal, tolerance and toxic levels of iron on human spermatozoa and mouse embryos were determined by challenging them with different levels of iron (ferric iron; Fe(+3)). Human normozoospermic semen samples (n=24) and days 1-4 Quakenbush Special (Qs) mouse embryos (n=1160) were incubated in PFM supplemented with different concentrations of Fe(+3) over different periods of time. 2.0μg/mL (35.8μM) of Fe(+3) was the optimal level of Fe(+3) for human spermatozoa with a tolerance range of 0.5-2μg/mL; whereas a level of 0.11μg/mL (2μM) of Fe(+3) was the optimum for day 2 embryos. Leve...
Reproductive biology, Jan 13, 2017
The objectives of this study is to evaluate the efficacy of protein-free media in the preparation... more The objectives of this study is to evaluate the efficacy of protein-free media in the preparation, holding and crypreservation of spermatazoa for use in ART. Normozoospermic semen samples (N=71) were used to compare the effects of media on the survival and quality of spermatozoa when washed and cultured with different media with and without added proteins at 4°C, 15°C, 22°C and 37°C for 0, 4-7 and 24h. Survival and quality of spermatozoa were assessed after freeze-thaw with synthetic cryoprotectant with and without proteins. Ethics/IRB approval was obtained (Ref. 1073.52). Spermatozoa parameters were similar in all media after washing and culture for 24h. Post-thaw survival and quality of spermatozoa was not significantly different 24h after thawing of samples frozen in all cryoprotectant medium. In conclusion synthetic protein-free culture and cryoprotectant media are equal in efficacy to protein-containing media in culture and cryopreservation of spermatozoa . Use of these synthet...
American journal of cancer research, 2016
Cancer-associated fibroblasts (CAFs) secrete various pro-tumorigenic cytokines, yet the role of t... more Cancer-associated fibroblasts (CAFs) secrete various pro-tumorigenic cytokines, yet the role of these cytokines in the progression of endometrial cancer remains unclear. We found that CAFs isolated from human endometrial cancer (EC) tissues secreted high levels of interleukin-6 (IL-6), which promotes EC cell proliferation in vitro. Neutralizing IL-6 in CAF-conditioned media reduced (47% inhibition) while IL-6 recombinant protein increased cell proliferation (~2.4 fold) of both EC cell lines and primary cultures. IL-6 receptors (IL-6R and gp130) were expressed only in EC epithelial cells but not in CAF, indicating a one-way paracrine signaling. In the presence of CAF-conditioned media, Janus kinase/signal transducers and activators of transcription (JAK/STAT3) pathway was activated in EC cells. Treatment with JAK and STAT3 specific inhibitors, AD412 and STATTIC, respectively, significantly abrogated CAF-mediated cell proliferation, indicating the role of IL-6 activation in EC cell pr...
Cryobiology, 2017
Cryopreservation is the only existing method of storage of human adipose-derived stem cells (ASCs... more Cryopreservation is the only existing method of storage of human adipose-derived stem cells (ASCs) for clinical use. However, cryopreservation has been shown to be detrimental to ASCs, particularly in term of cell viability. To restore the viability of cryopreserved ASCs, it is proposed to culture the cells in a hypoxic condition. To this end, we aim to investigate the effect of hypoxia on the cryopreserved human ASCs in terms of not only cell viability, but also their growth and stemness properties, which have not been explored yet. In this study, human ASCs were cultured under four different conditions: fresh (non-cryopreserved) cells cultured in 1) normoxia (21% O2) and 2) hypoxia (2% O2) and cryopreserved cells cultured in 3) normoxia and 4) hypoxia. ASCs at passage 3 were subjected to assessment of viability, proliferation, differentiation, and expression of stemness markers and hypoxia-inducible factor-1 alpha (HIF-1α). We found that hypoxia enhances the viability and the proliferation rate of cryopreserved ASCs. Further, hypoxia upregulates HIF-1α in cryopreserved ASCs, which in turn activates chondrogenic genes to promote chondrogenic differentiation. In conclusion, hypoxic-preconditioned cryopreserved ASCs could be an ideal cell source for cartilage repair and regeneration.
Journal of tissue engineering and regenerative medicine, Aug 12, 2016
Cryopreservation represents an efficient way to preserve human mesenchymal stem cells (hMSCs) at ... more Cryopreservation represents an efficient way to preserve human mesenchymal stem cells (hMSCs) at early culture/passage, and allows pooling of cells to achieve sufficient cells required for off-the-shelf use in clinical applications, e.g. cell-based therapies and regenerative medicine. To fully apply cryopreserved hMSCs in a clinical setting, it is necessary to evaluate their biosafety, e.g. chromosomal abnormality and tumourigenic potential. To date, many studies have demonstrated that cryopreserved hMSCs display no chromosomal abnormalities. However, the tumourigenic potential of cryopreserved hMSCs has not yet been evaluated. In the present study, we cryopreserved human adipose-derived mesenchymal stem cells (hASCs) for 3 months, using a slow freezing method with various cryoprotective agents (CPAs), followed by assessment of the tumourigenic potential of the cryopreserved hASCs after thawing and subculture. We found that long-term cryopreserved hASCs maintained normal levels of t...
Carcinogenesis, Jan 29, 2015
Genome-wide association studies have identified 20 genomic regions associated with risk of epithe... more Genome-wide association studies have identified 20 genomic regions associated with risk of epithelial ovarian cancer (EOC), but many additional risk variants may exist. Here we evaluated associations between common genetic variants (single nucleotide polymorphisms (SNPs) and indels) in DNA repair genes and EOC risk. We genotyped 2896 common variants at 143 gene loci in DNA samples from 15,397 patients with invasive EOC and controls. We found evidence of associations with EOC risk for variants at FANCA, EXO1, E2F4, E2F2, CREB5 and CHEK2 genes (P ≤ 0.001). The strongest risk association was for CHEK2 SNP rs17507066 with serous EOC (P = 4.74 x 10(-7)). Additional genotyping and imputation of genotypes from the 1000 genomes project identified a slightly more significant association for CHEK2 SNP rs6005807 (r(2) with rs17507066=0.84, odds ratio (OR) 1.17, 95% CI 1.11-1.24, P = 1.1 x10(-7)). We identified 293 variants in the region with likelihood ratios of less than 1:100 for representin...
Nature communications, Jan 22, 2015
Genome-wide association studies have reported 11 regions conferring risk of high-grade serous epi... more Genome-wide association studies have reported 11 regions conferring risk of high-grade serous epithelial ovarian cancer (HGSOC). Expression quantitative trait locus (eQTL) analyses can identify candidate susceptibility genes at risk loci. Here we evaluate cis-eQTL associations at 47 regions associated with HGSOC risk (P≤10(-5)). For three cis-eQTL associations…
Nature Genetics, 2015
Genome-wide association studies have identified several risk associations for ovarian carcinomas ... more Genome-wide association studies have identified several risk associations for ovarian carcinomas (OC) but not for mucinous ovarian carcinomas (MOC). Genotypes from OC cases and controls were imputed into the 1000 Genomes Project reference panel. Analysis of 1,644 MOC cases and 21,693 controls identified three novel risk associations: rs752590 at 2q13 (P = 3.3 × 10 −8), rs711830 at 2q31.1 (P = 7.5 × 10 −12) and rs688187 at 19q13.2 (P = 6.8 × 10 −13). Expression Quantitative Trait Locus (eQTL) analysis in ovarian and colorectal tumors (which are histologically similar to MOC) identified significant eQTL associations for HOXD9 at 2q31.1 in ovarian (P = 4.95 × 10 −4 , FDR = 0.003) and colorectal (P = 0.01, FDR = 0.09) tumors, and for PAX8 at 2q13 in colorectal tumors (P = 0.03, FDR = 0.09). Chromosome conformation capture analysis identified interactions between the HOXD9 promoter and risk SNPs at 2q31.1. Overexpressing HOXD9 in MOC cells augmented the neoplastic phenotype. These findings provide the first evidence for MOC susceptibility variants and insights into the underlying biology of the disease. Ovarian carcinomas (OC) caused approximately 140,000 cancer deaths globally in 2008 1. Germline mutations in genes conferring high (BRCA1 and BRCA2) 2 and more moderate risk (e.g.,
Nature genetics, 2015
Genome-wide association studies (GWAS) have identified 12 epithelial ovarian cancer (EOC) suscept... more Genome-wide association studies (GWAS) have identified 12 epithelial ovarian cancer (EOC) susceptibility alleles. The pattern of association at these loci is consistent in BRCA1 and BRCA2 mutation carriers who are at high risk of EOC. After imputation to 1000 Genomes Project data, we assessed associations of 11 million genetic variants with EOC risk from 15,437 cases unselected for family history and 30,845 controls and from 15,252 BRCA1 mutation carriers and 8,211 BRCA2 mutation carriers (3,096 with ovarian cancer), and we combined the results in a meta-analysis. This new study design yielded increased statistical power, leading to the discovery of six new EOC susceptibility loci. Variants at 1p36 (nearest gene, WNT4), 4q26 (SYNPO2), 9q34.2 (ABO) and 17q11.2 (ATAD5) were associated with EOC risk, and at 1p34.3 (RSPO1) and 6p22.1 (GPX6) variants were specifically associated with the serous EOC subtype, all with P…
Biochemical and Biophysical Research Communications, 2014
Adipose-derived stem cells (ASCs) have been found adapted to a specific niche with low oxygen ten... more Adipose-derived stem cells (ASCs) have been found adapted to a specific niche with low oxygen tension (hypoxia) in the body. As an important component of this niche, oxygen tension has been known to play a critical role in the maintenance of stem cell characteristics. However, the effect of O 2 tension on their functional properties has not been well determined. In this study, we investigated the effects of O 2 tension on ASCs stemness, differentiation and proliferation ability. Human ASCs were cultured under normoxia (21% O 2) and hypoxia (2% O 2). We found that hypoxia increased ASC stemness marker expression and proliferation rate without altering their morphology and surface markers. Low oxygen tension further enhances the chondrogenic differentiation ability, but reduces both adipogenic and osteogenic differentiation potential. These results might be correlated with the increased expression of HIF-1a under hypoxia. Taken together, we suggest that growing ASCs under 2% O 2 tension may be important in expanding ASCs effectively while maintaining their functional properties for clinical therapy, particularly for the treatment of cartilage defects.
Obstetrics & Gynecology, 2006
OBJECTIVE: To determine coital incidence at term and to estimate its effect on labor onset and mo... more OBJECTIVE: To determine coital incidence at term and to estimate its effect on labor onset and mode of delivery. METHODS: Healthy women with uncomplicated pregnancies and established gestational age were recruited to keep a diary of coital activity from 36 weeks of gestation until birth and to answer a short questionnaire. Two hundred women with complete coital diaries were available for analysis. Outcome measures include coitus, postdate pregnancy (defined as pregnancy beyond the estimated date of confinement), gestational length of at least 41 weeks, labor induction at 41 weeks of gestation, and mode of delivery. RESULTS: Reported sexual intercourse at term was influenced by a woman's perception of coital safety, her ethnicity, and her partner's age. After multivariable logistic regression analysis controlling for the women's ethnicity, education, occupation, perception of coital safety, and partner's age, coitus at term remained independently associated with reductions in postdate pregnancy (adjusted odds ratio [AOR] 0.28, 95% confidence interval [CI] 0.13-0.58, P = .001), gestational length of at least 41 weeks (AOR 0.10, 95% CI 0.04-0.28, P < .001), and requirement for labor induction at 41 weeks of gestation (AOR 0.08, 95% CI 0.03-0.26, P < .001). At 39 weeks of gestation, 5 (95% CI 3.3-10.3) couples needed to have intercourse to avoid one woman having to undergo labor induction at 41 weeks of gestation. Coitus at term had no significant effect on operative delivery (adjusted P = .15). CONCLUSION: Reported sexual intercourse at term was associated with earlier onset of labor and reduced requirement for labor induction at 41 weeks.
Frontiers in Microbiology, 2014
Toxoplasma gondii, is one of the infectious agents of congenital TORCH infections, causes severe ... more Toxoplasma gondii, is one of the infectious agents of congenital TORCH infections, causes severe clinical outcomes in fetus and newborns. Nevertheless this life-threatening parasitic disease is preventable by simple preventive measures related to lifestyle during pregnancy. We aim to study on the knowledge about toxoplasmosis and practices that prevents this infection among the pregnant women. Total of 2598 pregnant women from Malaysia, Philippines, and Thailand were randomly surveyed to determine the knowledge and their practices on Toxoplasma infection. The questionnaire covered respondents' general information and knowledge on plausible risks factors, symptoms, timing of infection, prevention knowledge, and preventive behavior regarding Toxoplasma infection. Majority of these pregnant women were in their age group of 20-29 years (50.9%), completed secondary level of education (51.7%), in their second trimester of pregnancies (38.1%), non-parous (36.6%), and had no history of abortion (90.4%). Based on this survey, only 11% of these pregnant women had read, heard, or seen information regarding toxoplasmosis and 3.5% of them were aware of being tested for the infection. A small percentage of these pregnant women knew that T. gondii were shed in the feces of infected cats (19.4%) and sometimes found in the raw or undercooked meat (11.0%). There was 16.1% of responding women knew that toxoplasmosis is caused by an infection. Demographic profiles such as age group, level of education, pregnancy term, and number of children of the pregnant women showed significant association with their responses toward prevention knowledge and preventive behavior related questions (P < 0.05). Thus, it is suggested that health education on toxoplasmosis and primary behavioral practices should be consistently offered to reproductive age women in general and pregnant women in particular. This information could help to reduce vertical transmission of Toxoplasma infection during pregnancy.
Biomedical Imaging and Intervention Journal, 2010
Background: Transcatheter uterine artery embolisation (UAE) for the treatment of symptomatic fibr... more Background: Transcatheter uterine artery embolisation (UAE) for the treatment of symptomatic fibroids has been performed in several centres in the United States, Western Europe and Asia with promising results. This study reports the authors' experience with UAE at the University Malaya Medical Centre. Method: Fifty women with symptomatic uterine fibroids who declined surgery were treated by transcatheter UAE. The uterine arteries were selectively catheterised and embolised with polyvinyl alcohol particles. Post-procedure analgesia was administered via patientcontrolled analgesic pump. The patients were followed up at an interval of 6/12 clinically and with MRI. Results: Transcatheter UAE was performed on all 50 patients with no major complications. 49 patients had both uterine arteries embolised while 1 patient had only the right uterine artery embolised on account of hypoplasia of the left uterine artery due to previous myomectomy. The mean hospital stay was 3.5 days (range, 2 to 7). At a mean follow-up of 24/52, all patients reported improvements in their presenting symptoms. Objective improvement in terms of reduction of uterine and fibroid sizes was determined on MRI. One patient, who initially responded with a decrease in uterine and dominant fibroid size, became symptomatic (menorrhagia) after 6 months and subsequent endometrial sampling revealed cystic glandular hyperplasia for which total abdominal hysterectomy was performed. Two other patients had no change in symptoms and after hysterectomy, the pathology revealed concurrent adenomyosis. Another 2 patients with cervical fibroids were treated with hysterectomy as there was no gross reduction in the size of fibroid following UAE. Overall, 90% of the patients had dramatic improvement of anaemia and symptoms at 1 year follow-up. Conclusion: Out of the 50 patients, 17 patients had total disappearance of their fibroids and 28 patients had more than 50% reduction in the size of fibroids after 1 year. 5 patients ended up with total abdominal hysterectomy. These results suggest that UAE is an appealing alternative to hysterectomy or myomectomy for many women with symptomatic fibroids.
Journal of Health and Translational Medicine
To see the trend in managing singleton breech pregnancy after the term breech trial. Secondly to ... more To see the trend in managing singleton breech pregnancy after the term breech trial. Secondly to compare the safety of different modes of delivery for term, singleton breeches by looking at the immediate neonatal outcome, based on our own experience. Breech infants were identified by examining computer-stored maternal discharge records of hospitalization for the years 1990 and 2000 respectively. Parameters studied included planned mode of delivery, actual mode of delivery, parity, previous vaginal delivery, Apgar score at five minute, birth weight, referral to special care nursery and neonatal morbidity. Of 6,496 deliveries in 1990 and 5,081 in 2000, there were 220 (3.4%) and 148 (2.9%) term breech infants respectively, of which 115 (for 1990) and 102 (for 2000) case records were available. In 1990, 62.6% of the women had trial of vaginal breech delivery but only 24.5% of the women in 2000 were allowed to do so (p < 0.05). Caesarean section rate for singleton breeches increased from 51.3% in 1990 to 84.3% in 2000 (p < 0.05). Mean Apgar score at five minutes was significantly lower after vaginal breech delivery (9.40 ± 1.36) compared to after Caesarean section (9.72 ± 0.712) but there was no clinical significance. There was a noticeable trend towards Caesarean section and less trial of vaginal delivery. Neonatal outcomes of babies born abdominally were statistically better than those born vaginally but there was little clinical impact. Perhaps in properly selected cases, a planned vaginal breech delivery still has a role to play.
Nature Communications, Mar 2013
HNF1B is overexpressed in clear cell epithelial ovarian cancer, and we observed epigenetic silenc... more HNF1B is overexpressed in clear cell epithelial ovarian cancer, and we observed epigenetic silencing in serous epithelial ovarian cancer, leading us to hypothesize that variation in this gene differentially associates with epithelial ovarian cancer risk according to histological subtype. Here we comprehensively map variation in HNF1B with respect to epithelial ovarian cancer risk and analyse DNA methylation and expression profiles across histological subtypes. Different single-nucleotide polymorphisms associate with invasive serous (rs7405776 odds ratio (OR) = 1.13, P = 3.1 x 10(-10)) and clear cell (rs11651755 OR = 0.77, P = 1.6 x 10(-8)) epithelial ovarian cancer. Risk alleles for the serous subtype associate with higher HNF1B-promoter methylation in these tumours. Unmethylated, expressed HNF1B, primarily present in clear cell tumours, coincides with a CpG island methylator phenotype affecting numerous other promoters throughout the genome. Different variants in HNF1B associate with risk of serous and clear cell epithelial ovarian cancer; DNA methylation and expression patterns are also notably distinct between these subtypes. These findings underscore distinct mechanisms driving different epithelial ovarian cancer histological subtypes.
Sādhanā
Objective identification of pain due to uterine contraction during the first stage of labour usin... more Objective identification of pain due to uterine contraction during the first stage of labour using continuous EEG signals and SVM. Sadhana-Academy Proceedings in Engineering Sciences, 44(4), Article number: 87 1-12.
Taiwanese journal of obstetrics & gynecology, 2018
To validate the gene expression profile obtained from the previous microarray analysis and to fur... more To validate the gene expression profile obtained from the previous microarray analysis and to further study the biological functions of these genes in endometrial cancer. From our previous study, we identified 621 differentially expressed genes in laser-captured microdissected endometrioid endometrial cancer as compared to normal endometrial cells. Among these genes, 146 were significantly up-regulated in endometrial cancer. A total of 20 genes were selected from the list of up-regulated genes for the validation assay. The qPCR confirmed that 19 out of the 20 genes were up-regulated in endometrial cancer compared with normal endometrium. RNA interference (RNAi) was used to knockdown the expression of the upregulated genes in ECC-1 and HEC-1A endometrial cancer cell lines and its effect on proliferation, migration and invasion were examined. Knockdown of MIF, SOD2, HIF1A and SLC7A5 by RNAi significantly decreased the proliferation of ECC-1 cells (p < 0.05). Our results also showed...
Reproductive biology, Jan 23, 2017
A parallel group superiority prospective randomised controlled trial was devised to compare the c... more A parallel group superiority prospective randomised controlled trial was devised to compare the culture characteristics of human pre-implantation stage embryos during uninterrupted culture in a time lapse incubator (TLI) versus the conventional model of interrupted culture in a standard incubator (SI) under low oxygen tension using a single step medium. 221 patients aged 35-and-under, 124 patients aged between 36 and 39 and 86 patients aged 40-and-over years were randomised and cultured either in a SI or in a TLI. Patients in the three age groups were distributed between the TLI and SI in a 1:1 ratio. The development of embryos on days 2, 3 and 5, and the clinical pregnancy and implantation rates were recorded. The fertilisation rate, development of day 2 and clinical pregnancy rates were similar in both treatments but the 8-cell development rate in all age groups combined (p = 0.016), blastocyst development rate (p = 0.0022) and the implantation rate (p = 0.0022) was significantly ...
Journal of Obstetrics and Gynaecology Research
To evaluate the efficacy of acupressure at the Neiguan point (Pericardium [P]6) as adjuvant treat... more To evaluate the efficacy of acupressure at the Neiguan point (Pericardium [P]6) as adjuvant treatment during inpatient management of severe nausea and vomiting in pregnancy. Low risk, spontaneously conceived singleton pregnancies were randomly assigned to a treatment group, who received an acupressure band placed at the Neiguan point (P6) or a placebo group who received an otherwise identical non-stimulating wristband. Participants wore the band for 12 h daily for the first three days of admission. The primary outcome measure was the severity of symptoms of nausea, vomiting and retching, recorded according to Pregnancy-Unique Quantification of Emesis and Nausea score. There was a statistically significant improvement in Pregnancy-Unique Quantification of Emesis and Nausea scores from day 1 until day 3 of admission in the treatment group compared with the placebo. Patients who received Neiguan point acupressure also showed a significant improvement in their ketonuria scores. The treatment group required a shorter hospital stay compared with the placebo. The only reported side effect of the acupressure band was redness on the wrist. The use of the acupressure band at the Neiguan point (P6) for 12 h daily for three days for inpatients with hyperemesis gravidarum significantly reduced the symptoms of nausea, vomiting and retching and ketonuria and led to a reduction in hospital stay. We recommend the use of the acupressure band at the Neiguan point (P6) as an adjunct/supplementary therapy to co-exist with the standard care of management for hyperemesis gravidarum, particularly in low-risk pregnant women.
Reproductive biology, Jan 19, 2017
There is a paucity of studies on effect of iron in embryo culture procedures. This study aims to ... more There is a paucity of studies on effect of iron in embryo culture procedures. This study aims to ascertain the optimal, tolerance and toxic levels of iron in a protein-free embryo culture medium (PFM) to determine the effect of iron on embryonic development. The application of PFM in assisted reproductive technologies (ART) is intended to eliminate disease transmission and improve ART treatment outcome. The optimal, tolerance and toxic levels of iron on human spermatozoa and mouse embryos were determined by challenging them with different levels of iron (ferric iron; Fe(+3)). Human normozoospermic semen samples (n=24) and days 1-4 Quakenbush Special (Qs) mouse embryos (n=1160) were incubated in PFM supplemented with different concentrations of Fe(+3) over different periods of time. 2.0μg/mL (35.8μM) of Fe(+3) was the optimal level of Fe(+3) for human spermatozoa with a tolerance range of 0.5-2μg/mL; whereas a level of 0.11μg/mL (2μM) of Fe(+3) was the optimum for day 2 embryos. Leve...
Reproductive biology, Jan 13, 2017
The objectives of this study is to evaluate the efficacy of protein-free media in the preparation... more The objectives of this study is to evaluate the efficacy of protein-free media in the preparation, holding and crypreservation of spermatazoa for use in ART. Normozoospermic semen samples (N=71) were used to compare the effects of media on the survival and quality of spermatozoa when washed and cultured with different media with and without added proteins at 4°C, 15°C, 22°C and 37°C for 0, 4-7 and 24h. Survival and quality of spermatozoa were assessed after freeze-thaw with synthetic cryoprotectant with and without proteins. Ethics/IRB approval was obtained (Ref. 1073.52). Spermatozoa parameters were similar in all media after washing and culture for 24h. Post-thaw survival and quality of spermatozoa was not significantly different 24h after thawing of samples frozen in all cryoprotectant medium. In conclusion synthetic protein-free culture and cryoprotectant media are equal in efficacy to protein-containing media in culture and cryopreservation of spermatozoa . Use of these synthet...
American journal of cancer research, 2016
Cancer-associated fibroblasts (CAFs) secrete various pro-tumorigenic cytokines, yet the role of t... more Cancer-associated fibroblasts (CAFs) secrete various pro-tumorigenic cytokines, yet the role of these cytokines in the progression of endometrial cancer remains unclear. We found that CAFs isolated from human endometrial cancer (EC) tissues secreted high levels of interleukin-6 (IL-6), which promotes EC cell proliferation in vitro. Neutralizing IL-6 in CAF-conditioned media reduced (47% inhibition) while IL-6 recombinant protein increased cell proliferation (~2.4 fold) of both EC cell lines and primary cultures. IL-6 receptors (IL-6R and gp130) were expressed only in EC epithelial cells but not in CAF, indicating a one-way paracrine signaling. In the presence of CAF-conditioned media, Janus kinase/signal transducers and activators of transcription (JAK/STAT3) pathway was activated in EC cells. Treatment with JAK and STAT3 specific inhibitors, AD412 and STATTIC, respectively, significantly abrogated CAF-mediated cell proliferation, indicating the role of IL-6 activation in EC cell pr...
Cryobiology, 2017
Cryopreservation is the only existing method of storage of human adipose-derived stem cells (ASCs... more Cryopreservation is the only existing method of storage of human adipose-derived stem cells (ASCs) for clinical use. However, cryopreservation has been shown to be detrimental to ASCs, particularly in term of cell viability. To restore the viability of cryopreserved ASCs, it is proposed to culture the cells in a hypoxic condition. To this end, we aim to investigate the effect of hypoxia on the cryopreserved human ASCs in terms of not only cell viability, but also their growth and stemness properties, which have not been explored yet. In this study, human ASCs were cultured under four different conditions: fresh (non-cryopreserved) cells cultured in 1) normoxia (21% O2) and 2) hypoxia (2% O2) and cryopreserved cells cultured in 3) normoxia and 4) hypoxia. ASCs at passage 3 were subjected to assessment of viability, proliferation, differentiation, and expression of stemness markers and hypoxia-inducible factor-1 alpha (HIF-1α). We found that hypoxia enhances the viability and the proliferation rate of cryopreserved ASCs. Further, hypoxia upregulates HIF-1α in cryopreserved ASCs, which in turn activates chondrogenic genes to promote chondrogenic differentiation. In conclusion, hypoxic-preconditioned cryopreserved ASCs could be an ideal cell source for cartilage repair and regeneration.
Journal of tissue engineering and regenerative medicine, Aug 12, 2016
Cryopreservation represents an efficient way to preserve human mesenchymal stem cells (hMSCs) at ... more Cryopreservation represents an efficient way to preserve human mesenchymal stem cells (hMSCs) at early culture/passage, and allows pooling of cells to achieve sufficient cells required for off-the-shelf use in clinical applications, e.g. cell-based therapies and regenerative medicine. To fully apply cryopreserved hMSCs in a clinical setting, it is necessary to evaluate their biosafety, e.g. chromosomal abnormality and tumourigenic potential. To date, many studies have demonstrated that cryopreserved hMSCs display no chromosomal abnormalities. However, the tumourigenic potential of cryopreserved hMSCs has not yet been evaluated. In the present study, we cryopreserved human adipose-derived mesenchymal stem cells (hASCs) for 3 months, using a slow freezing method with various cryoprotective agents (CPAs), followed by assessment of the tumourigenic potential of the cryopreserved hASCs after thawing and subculture. We found that long-term cryopreserved hASCs maintained normal levels of t...
Carcinogenesis, Jan 29, 2015
Genome-wide association studies have identified 20 genomic regions associated with risk of epithe... more Genome-wide association studies have identified 20 genomic regions associated with risk of epithelial ovarian cancer (EOC), but many additional risk variants may exist. Here we evaluated associations between common genetic variants (single nucleotide polymorphisms (SNPs) and indels) in DNA repair genes and EOC risk. We genotyped 2896 common variants at 143 gene loci in DNA samples from 15,397 patients with invasive EOC and controls. We found evidence of associations with EOC risk for variants at FANCA, EXO1, E2F4, E2F2, CREB5 and CHEK2 genes (P ≤ 0.001). The strongest risk association was for CHEK2 SNP rs17507066 with serous EOC (P = 4.74 x 10(-7)). Additional genotyping and imputation of genotypes from the 1000 genomes project identified a slightly more significant association for CHEK2 SNP rs6005807 (r(2) with rs17507066=0.84, odds ratio (OR) 1.17, 95% CI 1.11-1.24, P = 1.1 x10(-7)). We identified 293 variants in the region with likelihood ratios of less than 1:100 for representin...
Nature communications, Jan 22, 2015
Genome-wide association studies have reported 11 regions conferring risk of high-grade serous epi... more Genome-wide association studies have reported 11 regions conferring risk of high-grade serous epithelial ovarian cancer (HGSOC). Expression quantitative trait locus (eQTL) analyses can identify candidate susceptibility genes at risk loci. Here we evaluate cis-eQTL associations at 47 regions associated with HGSOC risk (P≤10(-5)). For three cis-eQTL associations…
Nature Genetics, 2015
Genome-wide association studies have identified several risk associations for ovarian carcinomas ... more Genome-wide association studies have identified several risk associations for ovarian carcinomas (OC) but not for mucinous ovarian carcinomas (MOC). Genotypes from OC cases and controls were imputed into the 1000 Genomes Project reference panel. Analysis of 1,644 MOC cases and 21,693 controls identified three novel risk associations: rs752590 at 2q13 (P = 3.3 × 10 −8), rs711830 at 2q31.1 (P = 7.5 × 10 −12) and rs688187 at 19q13.2 (P = 6.8 × 10 −13). Expression Quantitative Trait Locus (eQTL) analysis in ovarian and colorectal tumors (which are histologically similar to MOC) identified significant eQTL associations for HOXD9 at 2q31.1 in ovarian (P = 4.95 × 10 −4 , FDR = 0.003) and colorectal (P = 0.01, FDR = 0.09) tumors, and for PAX8 at 2q13 in colorectal tumors (P = 0.03, FDR = 0.09). Chromosome conformation capture analysis identified interactions between the HOXD9 promoter and risk SNPs at 2q31.1. Overexpressing HOXD9 in MOC cells augmented the neoplastic phenotype. These findings provide the first evidence for MOC susceptibility variants and insights into the underlying biology of the disease. Ovarian carcinomas (OC) caused approximately 140,000 cancer deaths globally in 2008 1. Germline mutations in genes conferring high (BRCA1 and BRCA2) 2 and more moderate risk (e.g.,
Nature genetics, 2015
Genome-wide association studies (GWAS) have identified 12 epithelial ovarian cancer (EOC) suscept... more Genome-wide association studies (GWAS) have identified 12 epithelial ovarian cancer (EOC) susceptibility alleles. The pattern of association at these loci is consistent in BRCA1 and BRCA2 mutation carriers who are at high risk of EOC. After imputation to 1000 Genomes Project data, we assessed associations of 11 million genetic variants with EOC risk from 15,437 cases unselected for family history and 30,845 controls and from 15,252 BRCA1 mutation carriers and 8,211 BRCA2 mutation carriers (3,096 with ovarian cancer), and we combined the results in a meta-analysis. This new study design yielded increased statistical power, leading to the discovery of six new EOC susceptibility loci. Variants at 1p36 (nearest gene, WNT4), 4q26 (SYNPO2), 9q34.2 (ABO) and 17q11.2 (ATAD5) were associated with EOC risk, and at 1p34.3 (RSPO1) and 6p22.1 (GPX6) variants were specifically associated with the serous EOC subtype, all with P…
Biochemical and Biophysical Research Communications, 2014
Adipose-derived stem cells (ASCs) have been found adapted to a specific niche with low oxygen ten... more Adipose-derived stem cells (ASCs) have been found adapted to a specific niche with low oxygen tension (hypoxia) in the body. As an important component of this niche, oxygen tension has been known to play a critical role in the maintenance of stem cell characteristics. However, the effect of O 2 tension on their functional properties has not been well determined. In this study, we investigated the effects of O 2 tension on ASCs stemness, differentiation and proliferation ability. Human ASCs were cultured under normoxia (21% O 2) and hypoxia (2% O 2). We found that hypoxia increased ASC stemness marker expression and proliferation rate without altering their morphology and surface markers. Low oxygen tension further enhances the chondrogenic differentiation ability, but reduces both adipogenic and osteogenic differentiation potential. These results might be correlated with the increased expression of HIF-1a under hypoxia. Taken together, we suggest that growing ASCs under 2% O 2 tension may be important in expanding ASCs effectively while maintaining their functional properties for clinical therapy, particularly for the treatment of cartilage defects.
Obstetrics & Gynecology, 2006
OBJECTIVE: To determine coital incidence at term and to estimate its effect on labor onset and mo... more OBJECTIVE: To determine coital incidence at term and to estimate its effect on labor onset and mode of delivery. METHODS: Healthy women with uncomplicated pregnancies and established gestational age were recruited to keep a diary of coital activity from 36 weeks of gestation until birth and to answer a short questionnaire. Two hundred women with complete coital diaries were available for analysis. Outcome measures include coitus, postdate pregnancy (defined as pregnancy beyond the estimated date of confinement), gestational length of at least 41 weeks, labor induction at 41 weeks of gestation, and mode of delivery. RESULTS: Reported sexual intercourse at term was influenced by a woman's perception of coital safety, her ethnicity, and her partner's age. After multivariable logistic regression analysis controlling for the women's ethnicity, education, occupation, perception of coital safety, and partner's age, coitus at term remained independently associated with reductions in postdate pregnancy (adjusted odds ratio [AOR] 0.28, 95% confidence interval [CI] 0.13-0.58, P = .001), gestational length of at least 41 weeks (AOR 0.10, 95% CI 0.04-0.28, P < .001), and requirement for labor induction at 41 weeks of gestation (AOR 0.08, 95% CI 0.03-0.26, P < .001). At 39 weeks of gestation, 5 (95% CI 3.3-10.3) couples needed to have intercourse to avoid one woman having to undergo labor induction at 41 weeks of gestation. Coitus at term had no significant effect on operative delivery (adjusted P = .15). CONCLUSION: Reported sexual intercourse at term was associated with earlier onset of labor and reduced requirement for labor induction at 41 weeks.
Frontiers in Microbiology, 2014
Toxoplasma gondii, is one of the infectious agents of congenital TORCH infections, causes severe ... more Toxoplasma gondii, is one of the infectious agents of congenital TORCH infections, causes severe clinical outcomes in fetus and newborns. Nevertheless this life-threatening parasitic disease is preventable by simple preventive measures related to lifestyle during pregnancy. We aim to study on the knowledge about toxoplasmosis and practices that prevents this infection among the pregnant women. Total of 2598 pregnant women from Malaysia, Philippines, and Thailand were randomly surveyed to determine the knowledge and their practices on Toxoplasma infection. The questionnaire covered respondents' general information and knowledge on plausible risks factors, symptoms, timing of infection, prevention knowledge, and preventive behavior regarding Toxoplasma infection. Majority of these pregnant women were in their age group of 20-29 years (50.9%), completed secondary level of education (51.7%), in their second trimester of pregnancies (38.1%), non-parous (36.6%), and had no history of abortion (90.4%). Based on this survey, only 11% of these pregnant women had read, heard, or seen information regarding toxoplasmosis and 3.5% of them were aware of being tested for the infection. A small percentage of these pregnant women knew that T. gondii were shed in the feces of infected cats (19.4%) and sometimes found in the raw or undercooked meat (11.0%). There was 16.1% of responding women knew that toxoplasmosis is caused by an infection. Demographic profiles such as age group, level of education, pregnancy term, and number of children of the pregnant women showed significant association with their responses toward prevention knowledge and preventive behavior related questions (P < 0.05). Thus, it is suggested that health education on toxoplasmosis and primary behavioral practices should be consistently offered to reproductive age women in general and pregnant women in particular. This information could help to reduce vertical transmission of Toxoplasma infection during pregnancy.