ORCID Profile
0000-0002-7276-7839
Current Organisations
University of Queensland
,
Universidade Federal de Minas Gerais
,
Baker Heart and Diabetes Institute
,
University of Melbourne
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Publisher: Springer Science and Business Media LLC
Date: 16-10-2010
DOI: 10.1007/S00192-009-1011-X
Abstract: Few studies have examined associations of prepregnancy urinary incontinence (UI). Multicentre prospective pregnancy cohort study (n = 1,507) using standardised measures to assess frequency and severity of UI. Prevalence of UI increased from 10.8% in the 12 months before the index pregnancy to 55.9% in the third trimester. Stress incontinence (36.9%) and mixed incontinence (13.1%) were more common during pregnancy than urge incontinence alone (5.9%). UI before pregnancy was associated with childhood enuresis (adjusted odds ratio (AdjOR) = 2.4, 95% confidence interval (CI) 1.6-3.4), higher maternal body mass index (AdjOR = 2.3, 95% CI 1.4-3.8), and previous miscarriages or terminations (AdjOR = 1.6, 95% CI 1.1-2.3). The strongest predictor of incident UI in pregnancy was occasional leakage (less than once a month) before pregnancy (AdjOR = 3.6, 95% CI 2.8-4.7). Further research is needed to elucidate the complex interplay of prepregnancy and pregnancy-related factors in the aetiology of UI in nulliparous women.
Publisher: ACM
Date: 25-06-2020
Publisher: Elsevier BV
Date: 12-2012
DOI: 10.1016/J.NEUROBIOLAGING.2012.02.009
Abstract: Mutations in the gene encoding fused in sarcoma (FUS) are linked to amyotrophic lateral sclerosis (ALS), but the mechanisms by which these mutants trigger neurodegeneration remain unknown. Endoplasmic reticulum (ER) stress is increasingly recognized as an important and early pathway to motor neuron death in ALS. FUS is normally located in the nucleus but in ALS, FUS redistributes to the cytoplasm and forms inclusions. In this study, we investigated whether FUS induces ER stress in a motor neuron like cell line (NSC-34). We demonstrate that ER stress is triggered in cells expressing mutant FUS, and this is closely associated with redistribution of mutant FUS to the cytoplasm. Mutant FUS also colocalized with protein disulfide-isomerase (PDI), an important ER chaperone, in NSC-34 cells and PDI was colocalized with FUS inclusions in human ALS lumbar spinal cords, in both sporadic ALS and mutant FUS-linked familial ALS tissues. These findings implicate ER stress in the pathophysiology of FUS, and provide evidence for common pathogenic pathways in ALS linked to the ER.
Publisher: Elsevier BV
Date: 06-2018
Publisher: Wiley
Date: 21-01-2015
Abstract: To investigate the relationship between mode of delivery, perineal trauma and dyspareunia. Prospective cohort study. Six maternity hospitals in Melbourne, Australia. A total of 1507 nulliparous women recruited in the first and second trimesters of pregnancy. Data from baseline and postnatal questionnaires (3, 6, 12 and 18 months) were analysed using univariable and multivariable logistic regression. Study-designed self-report measure of dyspareunia at 18 months postpartum. In all, 1244/1507 (83%) women completed the baseline and all four postpartum questionnaires 1211/1237 (98%) had resumed vaginal intercourse by 18 months postpartum, with 289/1211 (24%) women reporting dyspareunia. Compared with women who had a spontaneous vaginal delivery with an intact perineum or unsutured tear, women who had an emergency caesarean section (adjusted odds ratio [aOR] 2.41, 95% confidence interval [95% CI] 1.4-4.0 P = 0.001), vacuum extraction (aOR 2.28, 95% CI 1.3-4.1 P = 0.005) or elective caesarean section (aOR 1.71, 95% CI 0.9-3.2 P = 0.087) had increased odds of reporting dyspareunia at 18 months postpartum, adjusting for maternal age and other potential confounders. Obstetric intervention is associated with persisting dyspareunia. Greater recognition and increased understanding of the roles of mode of delivery and perineal trauma in contributing to postpartum maternal morbidities, and ways to prevent postpartum dyspareunia where possible, are warranted.
Publisher: Informa UK Limited
Date: 13-09-2012
Publisher: American Chemical Society (ACS)
Date: 11-10-2022
Abstract: The design of novel, safe, and effective drugs to treat human diseases is a challenging venture, with toxicity being one of the main sources of attrition at later stages of development. Failure due to toxicity incurs a significant increase in costs and time to market, with multiple drugs being withdrawn from the market due to their adverse effects. Cardiotoxicity, for instance, was responsible for the failure of drugs such as fenspiride, propoxyphene, and valdecoxib. While significant effort has been dedicated to mitigate this issue by developing computational approaches that aim to identify molecules likely to be toxic, including quantitative structure-activity relationship models and machine learning methods, current approaches present limited performance and interpretability. To overcome these, we propose a new web-based computational method, cardioToxCSM , which can predict six types of cardiac toxicity outcomes, including arrhythmia, cardiac failure, heart block, hERG toxicity, hypertension, and myocardial infarction, efficiently and accurately. cardioToxCSM was developed using the concept of graph-based signatures, molecular descriptors, toxicophore matchings, and molecular fingerprints, leveraging explainable machine learning, and was validated internally via different cross validation schemes and externally via low-redundancy blind sets. The models presented robust performances with areas under ROC curves of up to 0.898 on 5-fold cross-validation, consistent with metrics on blind tests. Additionally, our models provide interpretation of the predictions by identifying whether substructures that are commonly enriched in toxic compounds were present. We believe cardioToxCSM will provide valuable insight into the potential cardiotoxicity of small molecules early on drug screening efforts. The method is made freely available as a web server at biosig.lab.uq.edu.au/cardiotoxcsm.
Publisher: Elsevier BV
Date: 08-2016
DOI: 10.1016/J.WOMBI.2016.05.008
Abstract: The World Health Organisation recommends exclusive breastfeeding to six months postpartum, but most women in developed countries do not breastfeed this long. Prior studies exploring the relationship between breastfeeding duration and maternal depression show ambiguous findings. To explore associations between maternal depressive symptoms at three months postpartum, and breastfeeding status over the first six months postpartum. Prospective pregnancy cohort study of nulliparous women. 1507 women were recruited from six public hospitals in early pregnancy, completing baseline data in early pregnancy (mean gestation 15 weeks). Follow-up questionnaires were completed at three and six months postpartum. Women reported how many months they breastfed for (breastfeeding refers to 'any' breastfeeding, including expressed breastmilk). Depressive symptoms were measured at three months postpartum with the Edinburgh Postnatal Depression Scale (scores ≥13 indicated probable major depression). Of the almost 95% of women who initiated breastfeeding, 76% were still breastfeeding at three months postpartum, and by six months postpartum this dropped to 61%. Women who reported depressive symptoms at three months had significantly lower rates of breastfeeding at six months postpartum compared to women without depressive symptoms (49% vs. 61% adjusted OR=0.55, 95% CI 0.34-0.90). Maternal social characteristics associated with not breastfeeding at six months postpartum were: young maternal age lower education and smoking in pregnancy. Women's decisions around infant-feeding are influenced by a range of psycho-social factors, and early postnatal depressive symptoms appear to be a significant part of this picture, as either a cause or consequence of decisions to cease breastfeeding.
Publisher: American Chemical Society (ACS)
Date: 02-07-2021
Publisher: ACM
Date: 06-07-2013
Publisher: IEEE
Date: 11-2010
Publisher: Elsevier BV
Date: 03-2016
DOI: 10.1016/J.MIDW.2016.01.012
Abstract: to describe the frequency, severity and persistence of dyspareunia in the first 18 months after the birth of a first child. prospective pregnancy cohort study. Melbourne, Victoria, Australia. 1507 nulliparous women. women ≤24 weeks gestation were recruited from six public hospitals. Self-administered written questionnaires were completed at recruitment and at three, six, 12 and 18 months post partum. study-designed self-report measure of dyspareunia on first vaginal sex, and on second and subsequent sex at all time-points, utilising the rating scale from the McGill Pain Intensity Scale. overall, 961/1122 (85.7%) of women experienced pain on first vaginal sex postnatally. The proportion of women experiencing dyspareunia reduced over time, from 431/964 (44.7%) at three months post partum to 261/1155 (22.6%) at 18 months post partum. Of the women who reported dyspareunia at each time-point, around 10% of women described the pain as׳distressing׳,׳horrible׳ or׳excruciating׳. Women who had a caesarean section were more likely to report more intense dyspareunia at six months post partum (aOR=2.35, 95% CI=1.2-4.6). postnatal dyspareunia decreases over time, but persists beyond 12 months for one in five women. Caesarean section appears to be associated with more intense dyspareunia.
Publisher: Cold Spring Harbor Laboratory
Date: 29-07-2021
DOI: 10.1101/2021.07.28.454182
Abstract: Developmental and epileptic encephalopathies (DEEs) are a group of epilepsies with early onset and severe symptoms that sometimes lead to death. While a number of genes have been successfully implicated, it remains challenging to identify causative mutations within these genes from the background variation present in all in iduals due to disease heterogeneity. Our ability to detect likely pathogenic variants has continued to improve as in silico predictors of deleteriousness have advanced. We investigate their use in prioritising likely pathogenic variants in epileptic encephalopathy patient whole exome sequences and show that the inclusion of structure-based predictors of intolerance improve upon previous attempts to demonstrate enrichment within epilepsy genes.
Publisher: Springer International Publishing
Date: 2014
Publisher: Wiley
Date: 18-11-2008
Publisher: Institute of Electrical and Electronics Engineers (IEEE)
Date: 03-2012
Publisher: ACM
Date: 15-07-2017
Publisher: Springer Science and Business Media LLC
Date: 11-04-2006
Abstract: In the first year after childbirth, 94% of women experience one or more major health problems (urinary incontinence, faecal incontinence, perineal pain, back pain). Difficulties in intimate partner relationships and changes affecting sexual health are also common. The aim of this study is to investigate changes in women's health from early pregnancy until four years after the birth of a first child. The Maternal Health Study is a longitudinal study designed to fill in some of the gaps in current research evidence regarding women's physical and psychological health and recovery after childbirth. A prospective pregnancy cohort of nulliparous women has been recruited in early pregnancy at six metropolitan public hospitals in Melbourne, Australia between April 2003 and December 2005. In the first phase of the study participants are being followed up at 30–32 weeks gestation in pregnancy, and at three, six, nine, 12 and 18 months postpartum using a combination of self-administered questionnaires and telephone interviews. Women consenting to extended follow-up (phase 2) will be followed up six and 12 months after any subsequent births and when their first child is four years old. Study instruments incorporate assessment of the frequency and severity of urinary and bowel symptoms, sexual health issues, perineal and abdominal pain, depression and intimate partner violence. Pregnancy and birth outcome data will be obtained by review of hospital case notes. Features of the study which distinguish it from prior research include: the capacity to identify incident cases of morbidity and clustering of health problems a large enough s le to detect clinically important differences in maternal health outcomes associated with the method of birth careful exposure measurement involving manual abstraction of data from medical records in order to explore mediating factors and possible causal pathways and use of a variety of strategies to improve ascertainment of health outcomes.
Publisher: Wiley
Date: 15-10-2015
DOI: 10.1111/BIRT.12193
Abstract: Postnatal sexual health remains underresearched. The main aims of this study were to investigate the prevalence of postnatal sexual health issues, and the extent to which primary care practitioners routinely inquire about sexual health issues. 1,507 first time mothers were recruited in early pregnancy and followed up at 3, 6, and 12 months postpartum. Sexual health issues were assessed at every follow-up using a checklist. Eighty-nine percent of women reported sexual health issues in the first 3 months postpartum. The most common sexual health issues at 3 months postpartum were: loss of interest in sex, pain during sex, vaginal tightness, and lack of lubrication. Fifty-one percent continued to report loss of interest in sex at 12 months postpartum, and around 30 percent reported persisting pain. Although most women had contact with primary care practitioners during the first 3 months postpartum, only 24 percent recalled being asked about sexual health issues by general practitioners and 14 percent by maternal and child health nurses. Women who had a cesarean delivery had equivalent or higher odds of reporting persisting sexual health issues, but had lower odds of being asked directly about sexual problems (OR 0.58 [95% CI 0.4-0.9]). Sexual health issues are extremely common after childbirth. There was no evidence that women who had a cesarean delivery experienced fewer sexual health problems. Despite frequent contact with health professionals, women rarely discussed sexual health issues unless health professionals asked them directly. Given the high prevalence of postpartum sexual health issues routine inquiry is warranted.
Publisher: Oxford University Press (OUP)
Date: 23-08-2022
DOI: 10.1093/BIB/BBAC337
Abstract: Drug discovery is a lengthy, costly and high-risk endeavour that is further convoluted by high attrition rates in later development stages. Toxicity has been one of the main causes of failure during clinical trials, increasing drug development time and costs. To facilitate early identification and optimisation of toxicity profiles, several computational tools emerged aiming at improving success rates by timely pre-screening drug candidates. Despite these efforts, there is an increasing demand for platforms capable of assessing both environmental as well as human-based toxicity properties at large scale. Here, we present toxCSM, a comprehensive computational platform for the study and optimisation of toxicity profiles of small molecules. toxCSM leverages on the well-established concepts of graph-based signatures, molecular descriptors and similarity scores to develop 36 models for predicting a range of toxicity properties, which can assist in developing safer drugs and agrochemicals. toxCSM achieved an Area Under the Receiver Operating Characteristic (ROC) Curve (AUC) of up to 0.99 and Pearson’s correlation coefficients of up to 0.94 on 10-fold cross-validation, with comparable performance on blind test sets, outperforming all alternative methods. toxCSM is freely available as a user-friendly web server and API at biosig.lab.uq.edu.au/toxcsm.
Publisher: Springer Science and Business Media LLC
Date: 26-08-2016
DOI: 10.1007/S00737-016-0659-8
Abstract: The purpose of this study was to investigate intergenerational patterns of abuse and trauma and the health consequences for women in the early childbearing years. A prospective pregnancy cohort of 1507 nulliparous women (≦24 weeks gestation) were recruited in Melbourne, Australia, 2003-2005. Follow-up was scheduled in late pregnancy, 3-, 6- and 12-month and 4-year postpartum. Childhood abuse was retrospectively reported at 4-year postpartum using the Child Maltreatment History Self Report. Intimate partner violence (IPV) was assessed at 1- and 4-year postpartum with the Composite Abuse Scale. Maternal depressive symptoms were assessed in all follow-ups using the Edinburgh Postnatal Depression Scale. Multivariable logistic regression was used to examine associations between childhood abuse, maternal mental health and IPV. Childhood abuse was reported by 41.1 % of women. In the 4 years after having their first child, 28.2 % of women reported IPV, 25.2 % depression and 31.6 % anxiety. Childhood abuse was associated with odds of depression or anxiety 1.5-2.6 times greater and 1.8-3.2 times greater for IPV. Childhood physical abuse remained significantly associated with depression and anxiety in pregnancy and postpartum after adjusting for IPV and stressful life events, while sexual abuse remained significantly associated only with anxiety. Women who begin childbearing with a history of childhood abuse are more vulnerable to IPV and poor mental health. All health care services and agencies in contact with children, young people and families should have adequate training to identify trauma associated with abuse and IPV and provide first line supportive care and referral.
Publisher: Wiley
Date: 27-02-2013
Abstract: To investigate the timing of resumption of vaginal sex and assess associations with method of birth, perineal trauma and other obstetric and social factors. Prospective pregnancy cohort study of nulliparous women. Melbourne, Australia. A total of 1507 nulliparous women recruited in early pregnancy (≤24 weeks). Women were recruited from six public hospitals. Data from hospital records and self-administered questionnaires at recruitment and 3, 6 and 12 months postpartum were analysed using univariable and multivariable logistic regression. Resumption of vaginal sex. Sexual activity was resumed earlier than vaginal sex, with 53% resuming sexual activity by 6 weeks postpartum, and 41% attempting vaginal sex. By 8 weeks a majority of women had attempted vaginal sex (65%), increasing to 78% by 12 weeks, and 94% by 6 months. Compared with women who had a spontaneous vaginal birth with an intact perineum, women who had a spontaneous vaginal birth with an episiotomy (adjusted odds ratio 3.43, 95% confidence interval 1.9-6.2) or sutured perineal tear (adjusted odds ratio 3.18, 95% confidence interval 2.1-4.9) were more likely not to have resumed vaginal sex by 6 weeks postpartum. Similarly, women who had an assisted vaginal birth or caesarean section had raised odds of delaying resumption of sex. Most women having a first birth do not resume vaginal sex until later than 6 weeks postpartum. Women who have an operative vaginal birth, caesarean section or perineal tear or episiotomy appear to delay longer.
Publisher: Elsevier BV
Date: 2022
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 05-2015
Publisher: Wiley
Date: 14-07-2015
Abstract: To investigate frequency, severity and risk factors for urinary incontinence and faecal incontinence 4 years after a first birth. Prospective pregnancy cohort study. Melbourne, Australia. A total of 1011 nulliparous women recruited in early pregnancy. Participants were followed up at 32 weeks of gestation then at 3, 6, 9 and 12 months and 4 years postpartum. Frequency and severity of urinary and faecal incontinence. At 4 years, 29.6% of women reported urinary incontinence and 7.1% reported faecal incontinence. Compared with women having only spontaneous vaginal births, women who delivered exclusively by caesarean section were less likely to have urinary incontinence at 4 years postpartum (adjusted odds ratio 0.4, 95% confidence interval 0.3-0.6). Women who reported urinary incontinence before or during the index pregnancy, and those experiencing symptoms in the first year postpartum had increased odds of incontinence at 4 years, with the highest odds (6-12 times higher) among women who had previously reported moderate or severe symptoms. The odds of reporting faecal incontinence at 4 years were two to six times higher for women experiencing symptoms in pregnancy, and around four to eight times higher for those with symptoms in the first year postpartum. Urinary and faecal incontinence are prevalent conditions 4 years after a first birth. Women reporting urinary or faecal incontinence during pregnancy had markedly higher odds of reporting symptoms at 4 years postpartum, suggesting a need for further investigation and elucidation of aetiological pathways involving nonbirth-related risk factors. Moderate/severe incontinence prevalent 4 years after first birth in population cohort. Prior symptoms are biggest predictor.
Publisher: Springer International Publishing
Date: 2018
Publisher: Springer International Publishing
Date: 2020
Publisher: Springer International Publishing
Date: 2017
Publisher: Elsevier BV
Date: 12-2021
Publisher: ACM
Date: 18-11-2014
Publisher: Springer Science and Business Media LLC
Date: 19-08-2020
No related grants have been discovered for Alex de Sá.