ORCID Profile
0000-0002-9617-0826
Current Organisation
University of Adelaide
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Publisher: SAGE Publications
Date: 22-02-2022
DOI: 10.1177/19322968221079867
Abstract: The Environmental Determinants of Islet Autoimmunity (ENDIA) study is an Australia-wide pregnancy-birth cohort study following children who have a first-degree relative with type 1 diabetes (ACTRN1261300794707). A dedicated ENDIA Facebook page was established in 2013 with the aim of enhancing recruitment and supporting participant retention through dissemination of study information. To measure the impact of Facebook, we evaluated the sources of referral to the study, cohort demographics, and withdrawal rates. We also investigated whether engagement with Facebook content was associated with specific post themes. Characteristics of Facebook versus conventional recruits were compared using linear, logistic, and multinomial logistic regression models. Logistic regression was used to determine the risk of study withdrawal. Data pertaining to 794 Facebook posts over 7.5 years were included in the analysis. Facebook was the third largest source of referral (300/1511 19.9%). Facebook recruits were more frequently Australian-born ( P .001) enrolling postnatally ( P = .01) and withdrew from the study at a significantly lower rate compared with conventional recruits (4.7% vs 12.3% P .001) after a median of follow-up of 3.3 years. Facebook content featuring stories and images of participants received the highest engagement even though % of the 2337 Facebook followers were enrolled in the study. Facebook was a valuable recruitment tool for ENDIA. Compared with conventional recruits, Facebook recruits were three times less likely to withdraw during long-term follow-up and had different sociodemographic characteristics. Facebook content featuring participants was the most engaging. These findings inform social media strategies for future cohort and type 1 diabetes studies. Australia New Zealand Clinical Trials Registry: ACTRN1261300794707.
Publisher: Elsevier BV
Date: 05-2019
Publisher: Springer Science and Business Media LLC
Date: 12-03-2018
DOI: 10.1038/S41598-018-22491-7
Abstract: To optimise fecal s ling for reproducible analysis of the gut microbiome, we compared different methods of s le collection and sequencing of 16S rRNA genes at two centers. S les collected from six in iduals on three consecutive days were placed in commercial collection tubes (OMNIgeneGut OMR-200) or in sterile screw-top tubes in a home fridge or home freezer for 6–24 h, before transfer and storage at −80 °C. Replicate s les were shipped to centers in Australia and the USA for DNA extraction and sequencing by their respective PCR protocols, and analysed with the same bioinformatic pipeline. Variation in gut microbiome was dominated by differences between in iduals. Minor differences in the abundance of taxa were found between collection-processing methods and day of collection, and between the two centers. We conclude that collection with storage and transport at 4 °C within 24 h is adequate for 16S rRNA analysis of the gut microbiome. Other factors including differences in PCR and sequencing methods account for relatively minor variation compared to differences between in iduals.
Publisher: Elsevier BV
Date: 05-2014
DOI: 10.1016/J.BBAPAP.2014.01.018
Abstract: The timely detection of gastric cancer will contribute significantly towards effective treatment and is aided by the availability and reliability of appropriate biomarkers. A combination of several biomarkers can improve the sensitivity and specificity of cancer detection and this work reports results from a panel of 4 proteins. By combining a validated preclinical mouse model with a proteomic approach we have recently discovered novel biomarkers for the detection of gastric cancer. Here, we investigate the specificity of four of those biomarkers (afamin, clusterin, VDBP and haptoglobin) for the detection of gastric cancer using two independent methods of validation: ELISA, and a non antibody based method: Multiple Reaction Monitoring with High Resolution Mass Spectrometry (MRM-HR). All four biomarkers reliably differentiated GC from benign patient serum, and also in a small cohort of 11 early stage cases. We also present a novel isoform specific biomarker alpha-1-antitrypsin (A1AT) that was identified using a mouse model for gastric cancer. This isoform is distinct in charge and mobility in a pH gradient and was validated using human s les by isoelectric focussing and Western-blot (IEF-WB). This article is part of a Special Issue entitled: Biomarkers: A Proteomic Challenge.
Publisher: Hindawi Limited
Date: 15-08-2016
DOI: 10.1111/PEDI.12425
Abstract: The incidence of type 1 diabetes globally has increased dramatically over the last 50 years. Proposed environmental reasons for this increase mirror the modern lifestyle. Type 1 diabetes can be viewed as part of the non- communicable disease epidemic in our modern society. Meanwhile rapidly evolving new technologies are advancing our understanding of how human microbial communities interface with the immune system and metabolism, and how the modern pro-inflammatory environment is changing these communities and contributing to the rapid rise of non-communicable disease. The majority of children who present with clinical type 1 diabetes are of school age however 80% of children who develop type 1 diabetes by 18 years of age will have detectable islet autoantibodies by 3 years of age. The evolving concept that type 1 diabetes in many children has developmental origins has directed research questions in search of prevention back to pregnancy and early life. To this end the world's first pregnancy to early childhood cohort study in at-risk children has commenced.
Publisher: Hindawi Limited
Date: 20-05-2019
DOI: 10.1111/PEDI.12865
Abstract: To investigate the longitudinal relationship between the gut microbiome, circulating short chain fatty acids (SCFAs) and intestinal permeability in children with islet autoimmunity or type 1 diabetes and controls. We analyzed the gut bacterial microbiome, plasma SCFAs, small intestinal permeability and dietary intake in 47 children with islet autoimmunity or recent-onset type 1 diabetes and in 41 unrelated or sibling controls over a median (range) of 13 (2-34) months follow-up. Children with multiple islet autoantibodies (≥2 IA) or type 1 diabetes had gut microbiome dysbiosis. Anti-inflammatory Prevotella and Butyricimonas genera were less abundant and these changes were not explained by differences in diet. Small intestinal permeability measured by blood lactulose:rhamnose ratio was higher in type 1 diabetes. Children with ≥2 IA who progressed to type 1 diabetes (progressors), compared to those who did not progress, had higher intestinal permeability (mean [SE] difference +5.14 [2.0], 95% confidence interval [CI] 1.21, 9.07, P = .006), lower within-s le (alpha) microbial ersity (31.3 [11.2], 95% CI 9.3, 53.3, P = .005), and lower abundance of SCFA-producing bacteria. Alpha ersity (observed richness) correlated with plasma acetate levels in all groups combined (regression coefficient [SE] 0.57 [0.21], 95% CI 0.15, 0.99 P = .008). Children with ≥2 IA who progress to diabetes, like those with recent-onset diabetes, have gut microbiome dysbiosis associated with increased intestinal permeability. Interventions that expand gut microbial ersity, in particular SCFA-producing bacteria, may have a role to decrease progression to diabetes in children at-risk.
Publisher: Humana Press
Date: 2012
DOI: 10.1007/978-1-61779-573-2_22
Abstract: Labeling of exposed cell surface proteins of live cells using CyDye DIGE fluor minimal dyes is an efficient strategy for cell surface proteome profiling and quantifying differentially expressed proteins in diseases. Here we describe a strategy to evaluate a two-step detergent-based protein fractionation method using live cell labeling followed by visualization of the fluorescently labeled cell surface proteins and fractionated proteins within a single 2D gel.
Publisher: Springer Science and Business Media LLC
Date: 27-08-2019
DOI: 10.1007/S00125-019-4942-X
Abstract: The incidence of type 1 diabetes has increased since the mid-twentieth century at a rate that is too rapid to be attributed to genetic predisposition alone. While the disease can occur at any age, mounting evidence from longitudinal cohort studies of at-risk children indicate that type 1 diabetes associated autoantibodies can be present from the first year of life, and that those who develop type 1 diabetes at a young age have a more aggressive form of the disease. This corroborates the hypothesis that environmental exposures in early life contribute to type 1 diabetes risk, whether related to maternal influences on the fetus during pregnancy, neonatal factors or later effects during infancy and early childhood. Studies to date show a range of environmental triggers acting at different time points, suggesting a multifactorial model of genetic and environmental factors in the pathogenesis of type 1 diabetes, which integrally involves a dialogue between the immune system and pancreatic beta cells. For ex le, breastfeeding may have a weak protective effect on type 1 diabetes risk, while use of an extensively hydrolysed formula does not. Additionally, exposure to being overweight pre-conception, both in utero and postnatally, is associated with increased risk of type 1 diabetes. Epidemiological, clinical and pathological studies in humans support a role for viral infections, particularly enteroviruses, in type 1 diabetes, but definitive proof is lacking. The role of the early microbiome and its perturbations in islet autoimmunity and type 1 diabetes is the subject of investigation in ongoing cohort studies. Understanding the interactions between environmental exposures and the human genome and metagenome, particularly across ethnically erse populations, will be critical for the development of future strategies for primary prevention of type 1 diabetes.
Publisher: Springer Science and Business Media LLC
Date: 06-08-2021
DOI: 10.1186/S40168-021-01104-Y
Abstract: The gut microbiome changes in response to a range of environmental conditions, life events and disease states. Pregnancy is a natural life event that involves major physiological adaptation yet studies of the microbiome in pregnancy are limited and their findings inconsistent. Pregnancy with type 1 diabetes (T1D) is associated with increased maternal and fetal risks but the gut microbiome in this context has not been characterized. By whole metagenome sequencing (WMS), we defined the taxonomic composition and function of the gut bacterial microbiome across 70 pregnancies, 36 in women with T1D. Women with and without T1D exhibited compositional and functional changes in the gut microbiome across pregnancy. Profiles in women with T1D were distinct, with an increase in bacteria that produce lipopolysaccharides and a decrease in those that produce short-chain fatty acids, especially in the third trimester. In addition, women with T1D had elevated concentrations of fecal calprotectin, a marker of intestinal inflammation, and serum intestinal fatty acid-binding protein (I-FABP), a marker of intestinal epithelial damage. Women with T1D exhibit a shift towards a more pro-inflammatory gut microbiome during pregnancy, associated with evidence of intestinal inflammation. These changes could contribute to the increased risk of pregnancy complications in women with T1D and are potentially modifiable by dietary means.
Publisher: Informa UK Limited
Date: 12-04-2023
Publisher: Wiley
Date: 20-09-2019
DOI: 10.1111/DME.14131
Abstract: A hypothesized mechanism for increased type 1 diabetes risk among caesarean births is lack of exposure to the vaginal microbiota. Children born by prelabour caesarean are not exposed to the vaginal microbiota, whereas caesarean births during labour (intrapartum) may be exposed. The aim of this study was to estimate type 1 diabetes risk among children born by caesarean compared with normal vaginal delivery. This whole-of-population study linked routinely collected, de-identified administrative data from the South Australian Early Childhood Data Project for all births from 1999 to 2013. Type 1 diabetes cases were identified using inpatient hospitalizations from 2001 to 2014 (ICD-10-AM codes E10-E109). Type 1 diabetes risk for caesarean was assessed by Cox regression using two models: (i) caesarean vs. vaginal and (ii) prelabour or intrapartum caesarean vs. vaginal. Analyses were adjusted for confounding and multiple imputation was used to address missing data. A total of 286 058 children born between 1999 and 2013 contributed to 2 200 252 person-years, of which 557 had type 1 diabetes. Of all births, 90 546 (31.7%) were caesarean, and of these 53.1% were prelabour and 46.9% intrapartum caesarean. Compared with vaginal delivery, the adjusted hazard ratio for type 1 diabetes was 1.05 [95% confidence interval (CI) 0.86-1.28) for caesarean, 1.02 (95% CI 0.79-1.32) for prelabour caesarean and 1.08 (95% CI 0.82-1.41) for intrapartum caesarean. There may be a small increased type 1 diabetes risk following caesarean, but confidence intervals included the null. The lower estimate for prelabour compared with intrapartum caesarean, and the potential for unmeasured confounding suggest that neonatal vaginal microbiota might not be involved in type 1 diabetes.
Publisher: American Chemical Society (ACS)
Date: 04-08-2004
DOI: 10.1021/ES049575C
Abstract: The flavonoid hesperetin (Hsp) contains aromatic rings substituted with hydroxyl and methoxyl groups, which activate it toward electrophilic attack and hence make it a potential surrogate for natural organic matter with respect to reactions with chlorine. This paper describes the chlorination pathway of Hsp, based on a combination of electrospray tandem mass spectrometry (MS/MS) and absorbance spectroscopy. When a solution containing Hsp is dosed with NaOCl at pH 7, chlorine substitution into Hsp occurs exclusively into the meta-dihydroxy substituted ring. The first two Cl atoms to enter the ring do so at the highly activated carbons that are each ortho to two oxygenated carbon atoms. These substitutions make the molecule more acidic, but do not change its primary structure or aromaticity. The third Cl atom that substitutes into the molecule does so at one of the previously chlorinated sites, destroying the aromaticity of the ring and altering the molecular properties more dramatically than do the first two. The absorbance spectra of Hsp and mono- and di-chlorinated Hsp are all very similar and are very distinct from that of trichlorinated Hsp. In particular, the latter is the only one of those species that absorbs visible light (in a characteristic band centered at approximately 422nm). Di- and trichloroHsp form even at low molar Cl/Hsp ratios, and can coexist with Hsp and monochloroHsp in neutral, aqueous solutions for at least 24 h in the absence of free chlorine. If free chlorine is present, the less-chlorinated species continue to acquire Cl, and trichloroHsp undergoes further reaction, until either the free chlorine or the trichloroHsp is fully depleted. The appearance of di- and trichloroHsp while substantial amounts of Hsp remain unreacted indicates that substitution of one or two Cl atoms into the ring facilitates the incorporation of yet more Cl into the ring. This autoacceleration of the chlorination process is hypothesized to be induced by the increase in acidity that accompanies Cl incorporation. Specifically, the increase in the acidity of the phenolic groups shifts the equilibrium toward the enolate anion, which is considered to be much more amenable to electrophilic attack than the enol.
Publisher: American Chemical Society (ACS)
Date: 17-03-2007
DOI: 10.1021/ES062268H
Abstract: Mechanisms of chlorination of natural organic matter (NOM) in surface water (Lake Washington) were explored via differential spectroscopy. Two types of differential spectra (overall and incremental) were generated for this water chlorinated at pH 7 using varying chlorine doses and reaction times. The differential spectra contain two kinetically and spectroscopically distinct components. One of these components is attributable to functional groups that react rapidly with chlorine, while the other reflects transformations of slowly reacting chromophores that arise following the depletion of the fast chromophores. Small concentrations of disinfection byproducts (DBPs), exemplified in this study by dichloroacetic acid and chloral hydrate, were produced during the initial phase of chlorination, when the fast-reacting chromophores were being consumed. Rather, the release of those DBPs was correlated with the breakdown of the slowly reacting chromophores.
Publisher: American Chemical Society (ACS)
Date: 23-04-2009
DOI: 10.1021/PR801111A
Abstract: A model for chronic corynetoxins poisoning has been established in rats exposed to the toxicologically bioequivalent inhibitor of N-linked glycosylation the tunicamycins. Consumption of corynetoxins in contaminated pasture can result in the often fatal neurological disease of grazing livestock annual ryegrass toxicity (ARGT). Corynetoxins may also threaten human health as potential contaminants of the food supply via grain or products derived from subclinically exposed animals. The serum proteomes of four dose groups plus a control group following 6, 9, and 12 months dietary tunicamycins exposure were compared by one-dimensional electrophoresis. Numerous differences were observed between the control and the highest dose group (40.5 mug tunicamycins/kg of body weight/day), designated as High). Accordingly, these s les were further examined using two-dimensional electrophoresis. Thirty-three protein spots were found to be differentially displayed between the Control and High dose sera based on univariate statistics (p < 0.05 for log(10) transformed normalized volumes) and significant fold-changes in spot volume (+/-2.3-fold as determined by posthoc power analysis). Identities for 28 spots were obtained by MALDI-TOF MS corresponding to 13 different proteins. An increasing population of carbohydrate deficient transferrin was identified in the High dose sera using a combination of antibody and lectin detection and confirmed by ESI-IT MS/MS. The functionalities of other identified proteins were consistent with the oxidative stress and acute phase responses. The biomarkers identified in this study may not only play a useful role in diagnosing toxin exposure but could be helpful in identifying new treatment strategies for ARGT and equivalent human diseases.
Publisher: MDPI AG
Date: 24-08-2021
DOI: 10.3390/IJMS22179129
Abstract: Background: Rural/remote blood collection can cause delays in processing, reducing PBMC number, viability, cell composition and function. To mitigate these impacts, blood was stored at 4 °C prior to processing. Viable cell number, viability, immune phenotype, and Interferon-γ (IFN-γ) release were measured. Furthermore, the lowest protective volume of cryopreservation media and cell concentration was investigated. Methods: Blood from 10 in iduals was stored for up to 10 days. Flow cytometry and IFN-γ ELISPOT were used to measure immune phenotype and function on thawed PBMC. Additionally, PBMC were cryopreserved in volumes ranging from 500 µL to 25 µL and concentration from 10 × 106 cells/mL to 1.67 × 106 cells/mL. Results: PBMC viability and viable cell number significantly reduced over time compared with s les processed immediately, except when stored for 24 h at RT. Monocytes and NK cells significantly reduced over time regardless of storage temperature. S les with h of RT storage had an increased proportion in Low-Density Neutrophils and T cells compared with s les stored at 4 °C. IFN-γ release was reduced after 24 h of storage, however not in s les stored at 4 °C for h. The lowest protective volume identified was 150 µL with the lowest density of 6.67 × 106 cells/mL. Conclusion: A s le delay of 24 h at RT does not impact the viability and total viable cell numbers. When long-term delays exist ( d) total viable cell number and cell viability losses are reduced in s les stored at 4 °C. Immune phenotype and function are slightly altered after 24 h of storage, further impacts of storage are reduced in s les stored at 4 °C.
Publisher: Elsevier BV
Date: 12-2019
Publisher: AMPCo
Date: 11-2016
DOI: 10.5694/MJA16.00685
Publisher: MDPI AG
Date: 29-03-2023
Abstract: Background: We sought research experiences of caregivers and their children were enrolled in the Environmental Determinants of Islet Autoimmunity (ENDIA) study. Methods: ENDIA is a pregnancy–birth cohort investigating early-life causes of type 1 diabetes (T1D). Surveys were sent to 1090 families between June 2021 and March 2022 with a median participation of years. Caregivers completed a 12-item survey. Children ≥ 3 years completed a four-item survey. Results: The surveys were completed by 550/1090 families (50.5%) and 324/847 children (38.3%). The research experience was rated as either “excellent” or “good” by 95% of caregivers, and 81% of children were either “ok”, “happy” or “very happy”. The caregivers were motivated by contributing to research and monitoring their children for T1D. Relationships with the research staff influenced the experience. The children most liked virtual reality headsets, toys, and “helping”. Blood tests were least liked by the children and were the foremost reason that 23.4% of the caregivers considered withdrawing. The children valued gifts more than their caregivers. Only 5.9% of responses indicated dissatisfaction with some aspects of the protocol. The self-collection of s les in regional areas, or during the COVID-19 pandemic restrictions, were accepted. Conclusions: This evaluation identified modifiable protocol elements and was conducted to further improve satisfaction. What was important to the children was distinct from their caregivers.
Publisher: Springer Science and Business Media LLC
Date: 14-08-2013
Abstract: The incidence of type 1 diabetes has increased worldwide, particularly in younger children and those with lower genetic susceptibility. These observations suggest factors in the modern environment promote pancreatic islet autoimmunity and destruction of insulin-producing beta cells. The Environmental Determinants of Islet Autoimmunity (ENDIA) Study is investigating candidate environmental exposures and gene-environment interactions that may contribute to the development of islet autoimmunity and type 1 diabetes. ENDIA is the only prospective pregnancy/birth cohort study in the Southern Hemisphere investigating the determinants of type 1 diabetes in at-risk children. The study will recruit 1,400 unborn infants or infants less than six months of age with a first-degree relative (i.e. mother, father or sibling) with type 1 diabetes, across five Australian states. Pregnant mothers/infants will be followed prospectively from early pregnancy through childhood to investigate relationships between genotype, the development of islet autoimmunity (and subsequently type 1 diabetes), and prenatal and postnatal environmental factors. ENDIA will evaluate the microbiome, nutrition, bodyweight/composition, metabolome-lipidome, insulin resistance, innate and adaptive immune function and viral infections. A systems biology approach will be used to integrate these data. Investigation will be by 3-monthly assessments of the mother during pregnancy, then 3-monthly assessments of the child until 24 months of age and 6-monthly thereafter. The primary outcome measure is persistent islet autoimmunity, defined as the presence of autoantibodies to one or more islet autoantigens on consecutive tests. Defining gene-environment interactions that initiate and/or promote destruction of the insulin-producing beta cells in early life will inform approaches to primary prevention of type 1 diabetes. The strength of ENDIA is the prospective, comprehensive and frequent systems-wide profiling from early pregnancy through to early childhood, to capture dynamic environmental exposures that may shape the development of islet autoimmunity. Australia New Zealand Clinical Trials Registry ACTRN12613000794707 .
Publisher: Elsevier BV
Date: 10-2012
DOI: 10.1016/J.RVSC.2011.08.015
Abstract: The neurological livestock disease annual ryegrass toxicity (ARGT) is caused by the ingestion of the naturally occurring glycolipid toxins - the corynetoxins. Corynetoxins also threaten human health as potential contaminants of the food supply. Presently, there are no routine diagnostic tests for corynetoxins-exposure in humans or livestock. Chronic ingestion of corynetoxins has been modeled in rats exposed to dietary tunicamycins for 12 months and carbohydrate deficient transferrin (CDT) has been previously identified as a candidate disease biomarker. Here, the technique of immuno-capture mass spectrometry (icMS) was used to evaluate serum levels of CDT, discriminating between control and tunicamycins-exposed rats with 85% accuracy. The icMS approach is based on the combination of specific transferrin enrichment with functionalized magnetic beads and automated matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). With no other clinically-relevant diagnostic tests available icMS could be readily adapted for high-throughput clinical assessment of corynetoxins-exposure in humans or livestock.
Publisher: JMIR Publications Inc.
Date: 04-10-2021
Abstract: ecruitment and retention of research participants is challenging. Social media, particularly Facebook, has emerged as a tool for connecting with participants due to its high uptake in the community. The Environmental Determinants of Islet Autoimmunity (ENDIA) study is an Australia-wide prospective pregnancy-birth cohort following children who have a first-degree relative with type 1 diabetes (ACTRN1261300794707). A dedicated Facebook page was established for the ENDIA study in 2013 with the aim to enhance recruitment and support participant retention. he purpose of this investigation was to evaluate the long-term impact of Facebook as a recruitment and retention tool. The hypotheses were that (1) Facebook was an important source of referral to the ENDIA study, (2) the sociodemographic characteristics of participants recruited by Facebook would be different from those of participants recruited by other means (i.e., ‘conventional recruits’), and (3) recruitment by Facebook would be associated with long-term retention. We also evaluated the most effective types of Facebook content based on post engagement. ecruitment of 1511 ENDIA participants was completed in December 2019. Characteristics of participants recruited through Facebook were compared to conventional recruits using linear, logistic, and multinomial logistic regression models. A logistic regression model was used to determine the risk of study withdrawal. Data pertaining to 794 Facebook posts over 7.5 years from June 2013 until December 2020 were extracted using the Facebook ‘Insights’ function for thematic analysis. acebook was the third largest source of referral to the ENDIA study (300/1511 19.9%) behind in-person clinics (500/1511, 33.1%) and healthcare professional referrals (347/1511, 23.0%). The ENDIA Facebook page had 2337 followers at the close of recruitment. Approximately 20% of these could be identified as participating parents. Facebook recruits were more frequently Australian-born (P .001) enrolling postnatally (P=.01) and withdrew from the study at a significantly lower rate compared to conventional recruits (4.7% vs 12.3% P .001) after a median of follow-up of 3.3 years. acebook was a valuable recruitment tool for the ENDIA study and participants recruited through Facebook were three times less likely to withdraw during long-term follow-up. The sociodemographic characteristics of Facebook recruits were different to conventional recruits, but perhaps in unintended ways. Facebook content featuring stories and images of participants received the highest engagement despite the fact that most Facebook followers were not enrolled in the study. These findings should inform social media strategies for future cohort studies involving pregnant women and young families, and for type 1 diabetes risk studies. ustralia New Zealand Clinical Trials Registry: ACTRN1261300794707 R2-0.1186/1471-2431-13-124
Publisher: Hindawi Limited
Date: 07-01-2020
DOI: 10.1111/PEDI.12952
Abstract: Microbial exposures in utero and early life shape the infant microbiome, which can profoundly impact on health. Compared to the bacterial microbiome, very little is known about the virome. We set out to characterize longitudinal changes in the gut virome of healthy infants born to mothers with or without type 1 diabetes using comprehensive virome capture sequencing. Healthy infants were selected from Environmental Determinants of Islet Autoimmunity (ENDIA), a prospective cohort of Australian children with a first-degree relative with type 1 diabetes, followed from pregnancy. Fecal specimens were collected three-monthly in the first year of life. Among 25 infants (44% born to mothers with type 1 diabetes) at least one virus was detected in 65% (65/100) of s les and 96% (24/25) of infants during the first year of life. In total, 26 genera of viruses were identified and >150 viruses were differentially abundant between the gut of infants with a mother with type 1 diabetes vs without. Positivity for any virus was associated with maternal type 1 diabetes and older infant age. Enterovirus was associated with older infant age and maternal smoking. We demonstrate a distinct gut virome profile in infants of mothers with type 1 diabetes, which may influence health outcomes later in life. Higher prevalence and greater number of viruses observed compared to previous studies suggests significant underrepresentation in existing virome datasets, arising most likely from less sensitive techniques used in data acquisition.
Publisher: Hindawi Limited
Date: 18-09-2020
DOI: 10.1111/PEDI.13107
Publisher: Springer Science and Business Media LLC
Date: 24-02-2020
Publisher: Humana Press
Date: 2012
DOI: 10.1007/978-1-61779-573-2_15
Abstract: Serum is unarguably the most used diagnostic fluid. As it circulates throughout the body, leakage peptides roteins from damaged and dying cells, host-response proteins including inflammatory mediators, and aberrant secretions from tumors and diseased tissues are released into serum, potentially providing a rich source of disease biomarkers. Here, a method for extending access to the serum proteome by removing highly abundant proteins prior to comparative two-dimensional difference gel electrophoresis (2D DIGE) and subsequent protein digestion for identification by mass spectrometry is described.
Publisher: American Diabetes Association
Date: 02-02-2022
DOI: 10.2337/DC21-2335
Abstract: Pregnancy and type 1 diabetes are each associated with increased anxiety and depression, but the combined impact on well-being is unresolved. We compared the mental health of women with and without type 1 diabetes during pregnancy and postpartum and examined the relationship between mental health and glycemic control. Participants were women enrolled from 2016 to 2020 in the Environmental Determinants of Islet Autoimmunity (ENDIA) study, a pregnancy to birth prospective cohort following children with a first-degree relative with type 1 diabetes. Edinburgh Postnatal Depression Scale (EPDS) and Perceived Stress Scale (PSS) were completed during the third trimester (T3) (median [interquartile range] 34 [32, 36] weeks) and postpartum (14 [13, 16] weeks) by 737 women (800 pregnancies) with (n = 518) and without (n = 282) type 1 diabetes. EPDS and PSS scores did not differ between women with and without type 1 diabetes during T3 and postpartum. EPDS scores were marginally higher in T3: predicted mean (95% CI) 5.7 (5.4, 6.1) than postpartum: 5.3 (5.0, 5.6), independent of type 1 diabetes status (P = 0.01). HbA1c levels in type 1 diabetes were 6.3% [5.8, 6.9%] in T3 and did not correlate with EPDS or PSS scores. Reported use of psychotropic medications was similar in women with (n = 44 of 518 [8%]) and without type 1 diabetes (n = 17 of 282 [6%]), as was their amount of physical activity. Overall, mental health in late pregnancy and postpartum did not differ between women with and without type 1 diabetes, and mental health scores were not correlated with glycemic control.
Publisher: Wiley
Date: 17-06-2020
DOI: 10.1111/DME.13987
Abstract: To measure pancreatic area and exocrine function in young children with recent-onset Type 1 diabetes to determine whether the exocrine pancreas is also affected in the pathophysiology of early childhood diabetes. Thirty-two children (14 boys) aged 5.5 (4.5, 7.3) median (IQR) years presenting with recent-onset Type 1 diabetes and 90 controls (44 boys) of similar age had ultrasound imaging of the pancreas. Children with Type 1 diabetes were receiving insulin and were without ketosis. Transverse and longitudinal areas of the pancreas were measured by digitalized outline. Pancreatic faecal elastase-1 was analysed using an enzyme-linked immunosorbent assay kit in recent-onset Type 1 diabetes and 38 first-degree relative control children. Pancreatic area and exocrine function were reduced in Type 1 diabetes. Mean transverse area (SD) in Type 1 diabetes was 6.82 cm Pancreatic area and accompanying subclinical exocrine function were reduced in very young children with recent-onset Type 1 diabetes. This supports changes in the exocrine pancreas in the pathophysiology of Type 1 diabetes presenting in early life.
Publisher: Wiley
Date: 28-07-2009
DOI: 10.1002/RCM.4167
Abstract: Mass spectrometry (MS) profiling of the proteome and peptidome for disease-associated patterns is a new concept in clinical diagnostics. The technique, however, is highly sensitive to external sources of variation leading to potentially unacceptable numbers of false positive and false negative results. Before MS profiling can be confidently implemented in a medical setting, standard experimental methods must be developed that minimize technical variance. Past studies of variance have focused largely on pre-analytical variation (i.e., s le collection, handling, etc.). Here, we examined how factors at the analytical stage including the matrix and solid-phase extraction influence MS profiling. Firstly, a standard peptide rotein s le was measured automatically by matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) MS across five consecutive days using two different preparation methods, dried droplet and s le/matrix, of four types of matrix: alpha-cyano-4-hydroxycinnamic acid (HCCA), sinapinic acid (SA), 2,5-dihydroxybenzoic acid (DHB) and 2,5-dihydroxyacetophenone (DHAP). The results indicated that the matrix preparation greatly influenced a number of key parameters of the spectra including repeatability (within-day variability), reproducibility (inter-day variability), resolution, signal strength, background intensity and detectability. Secondly, an investigation into the variance associated with C8 magnetic bead extraction of the standard s le prior to automated MS profiling demonstrated that the process did not adversely affect these same parameters. In fact, the spectra were generally more robust following extraction. Thirdly, the best performing matrix preparations were evaluated using C8 magnetic bead extracted human plasma. We conclude that the DHAP prepared according to the dried-droplet method is the most appropriate matrix to use when performing automated MS profiling.
Publisher: Wiley
Date: 19-07-2021
DOI: 10.1111/DME.14638
Publisher: Elsevier BV
Date: 02-2022
DOI: 10.1016/J.DIABRES.2022.109189
Abstract: Studies of the gut microbiome have focused on its bacterial composition. We aimed to characterize the gut fungal microbiome (mycobiome) across pregnancy in women with and without type 1 diabetes. Faecal s les (n = 162) were collected from 70 pregnant women (45 with and 25 without type 1 diabetes) across all trimesters. Fungi were analysed by internal transcribed spacer 1 licon sequencing. Markers of intestinal inflammation (faecal calprotectin) and intestinal epithelial integrity (serum intestinal fatty acid binding protein I-FABP), and serum antibodies to Saccharomyces cerevisiae (ASCA) were measured. Women with type 1 diabetes had decreased fungal alpha ersity by the third trimester, associated with an increased abundance of Saccharomyces cerevisiae that was inversely related to the abundance of the anti-inflammatory butyrate-producing bacterium Faecalibacterium prausnitzii. Women with type 1 diabetes had higher concentrations of calprotectin, I-FABP and ASCA. Women with type 1 diabetes exhibit a shift in the gut mycobiome across pregnancy associated with evidence of gut inflammation and impaired intestinal barrier function. The relevance of these findings to the higher rate of pregnancy complications in type 1 diabetes warrants further study.
Publisher: Elsevier BV
Date: 04-2012
DOI: 10.1016/J.IJCARD.2011.09.014
Abstract: The coronary slow flow phenomenon [CSFP] is a coronary microvascular disorder, characterized by delayed distal vessel opacification despite the absence of obstructive coronary artery disease. Patients frequently present with an acute coronary syndrome [ACS] although the pathophysiological mechanisms responsible are unknown. The aim of this study was to identify potential mechanisms for the ACS presentation associated with the CSFP using a plasma proteomic profiling approach. Plasma s les from nine CSFP subjects [56 ± 11years] were assayed for high sensitivity C-reactive protein [hsCRP], troponin T [TnT], creatine kinase [CK], and proteomic analyses (n=6), during an ACS presentation and one month later [chronic phase]. Proteomic analysis involved chromatographic depletion of abundant plasma proteins followed by two-dimensional differential gel electrophoresis [2-D DIGE]. Protein spots demonstrating ±1.5-fold change relative to the control were identified by mass spectrometry and two differentially expressed proteins were selected for validation via Western blotting. During the ACS presentation, hsCRP was elevated [ACS=14.9 ± 3.9 mg/L vs chronic=4.23 ± 1.37 mg/L, p=0.05] but TnT and CK levels were unchanged. Proteomic analysis identified six proteins that were significantly different in abundance between the acute and chronic s les. During the ACS presentation there was a 1.6 ± 0.13 fold increase in the anti-oxidant enzyme paraoxonase-1 and an increase in inflammatory proteins alpha-1-antichymotrypsin [1.65 ± 0.13 fold] and alpha-1-antitrypsin [2.5 ± 0.34 fold]. The latter was confirmed by Western blotting [1.33 ± 0.17 OD acute/chronic ratio, p=0.05]. The findings from this novel detailed approach, implicate an inflammatory/oxidative stress process in the pathogenesis of the ACS presentation associated with the CSFP. Future studies should further elucidate these mechanisms.
Publisher: Hindawi Limited
Date: 02-2021
DOI: 10.1111/PEDI.13178
Abstract: We aimed to characterize associations between diet and the gut microbiome and short chain fatty acid (SCFA) products in youth with islet autoimmunity or type 1 diabetes (IA/T1D) in comparison with controls. Eighty participants (25 diagnosed with T1D, 17 with confirmed IA, 38 sibling or unrelated controls) from the Australian T1D Gut Study cohort were studied (median [IQR] age 11.7 [8.9, 14.0] years, 43% female). A Food Frequency Questionnaire characterized daily macronutrient intake over the preceding 6 months. Plasma and fecal SCFA were measured by gas chromatography gut microbiome composition and ersity by 16S rRNA gene sequencing. A 10 g increase in daily carbohydrate intake associated with higher plasma acetate in IA/T1D (adjusted estimate +5.2 (95% CI 1.1, 9.2) μmol/L p = 0.01) and controls (adjusted estimate +4.1 [95% CI 1.7, 8.5] μmol/L p = 0.04). A 5 g increase in total fat intake associated with lower plasma acetate in IA/T1D and controls. A 5% increase in noncore (junk) food intake associated with reduced richness (adjusted estimate -4.09 [95%CI -7.83, -0.35] p = .03) and evenness (-1.25 [95% CI -2.00, -0.49] p < 0.01) of the gut microbiome in IA/T1D. Fiber intake associated with community structure of the microbiome in IA/T1D. Modest increments in carbohydrate and fat intake associated with plasma acetate in all youth. Increased junk food intake associated with reduced ersity of the gut microbiome in IA/T1D alone. These associations with the gut microbiome in IA/T1D support future efforts to promote SCFA by using dietary interventions.
Publisher: Hindawi Limited
Date: 09-06-2020
DOI: 10.1111/PEDI.13056
Publisher: Oxford University Press (OUP)
Date: 16-01-2019
DOI: 10.1093/OFID/OFZ025
Abstract: The importance of gut bacteria in human physiology, immune regulation, and disease pathogenesis is well established. In contrast, the composition and dynamics of the gut virome are largely unknown particularly lacking are studies in pregnancy. We used comprehensive virome capture sequencing to characterize the gut virome of pregnant women with and without type 1 diabetes (T1D), longitudinally followed in the Environmental Determinants of Islet Autoimmunity study. In total, 61 pregnant women (35 with T1D and 26 without) from Australia were examined. Nucleic acid was extracted from serial fecal specimens obtained at prenatal visits, and viral genomes were sequenced by virome capture enrichment. The frequency, richness, and abundance of viruses were compared between women with and without T1D. Two viruses were more prevalent in pregnant women with T1D: picobirnaviruses (odds ratio [OR], 4.2 95% confidence interval [CI], 1.0–17.1 P = .046) and tobamoviruses (OR, 3.2 95% CI, 1.1–9.3 P = .037). The abundance of 77 viruses significantly differed between the 2 maternal groups (≥2-fold difference P & .02), including 8 Enterovirus B types present at a higher abundance in women with T1D. These findings provide novel insight into the composition of the gut virome during pregnancy and demonstrate a distinct profile of viruses in women with T1D.
No related grants have been discovered for Megan Penno.