Background: Pregnancy in women with congenital heart disease (CHD) is associated with an increased risk of adverse maternal and fetal events. Despite the physiological impact of CHD on pregnancy, current risk stratification scores primarily consider anatomical lesions. We assessed the performance of the novel American Heart Association Anatomic and Physiological (AP) classification system in predicting adverse maternal cardiac, obstetric and fetal events, and compared it with established risk models.
View Article and Find Full Text PDFTranslational research is commonly performed in the C57B6/J mouse strain, chosen for its genetic homogeneity and phenotypic uniformity. Here, we evaluate the suitability of the white-footed deer mouse (Peromyscus leucopus) as a model organism for aging research, offering a comparative analysis against C57B6/J and diversity outbred (DO) Mus musculus strains. Our study includes comparisons of body composition, skeletal muscle function, and cardiovascular parameters, shedding light on potential applications and limitations of P.
View Article and Find Full Text PDFMicrogravity is associated with immunological dysfunction, though the mechanisms are poorly understood. Here, using single-cell analysis of human peripheral blood mononuclear cells (PBMCs) exposed to short term (25 hours) simulated microgravity, we characterize altered genes and pathways at basal and stimulated states with a Toll-like Receptor-7/8 agonist. We validate single-cell analysis by RNA sequencing and super-resolution microscopy, and against data from the Inspiration-4 (I4) mission, JAXA (Cell-Free Epigenome) mission, Twins study, and spleens from mice on the International Space Station.
View Article and Find Full Text PDFObjective: We report the prevalence, characteristics and clinical outcomes of women with sexually transmitted infections (STIs) in pregnancy in the Western Sydney Local Health District (WSLHD) serving a large culturally and socio-economically diverse community in New South Wales (NSW), Australia, over the last 10 years.
Methods: A retrospective cohort study of all pregnant women booked for antenatal care at three hospitals in WSLHD between September 2012 and August 2022 inclusive. Characteristics and birth outcomes associated with STIs diagnosed in pregnancy (chlamydia, gonorrhea, and syphilis) are reported using multivariable logistic regression adjusting for relevant confounders.
Background: The collection of data on 'infant feeding at hospital discharge' is used to monitor breastfeeding outcomes, health service benchmarking, and research. While some Australian states have clear definitions of this data collection point, there is no operational definition of 'infant feeding at hospital discharge' in the Australian state of New South Wales. Little is known about how midwives interpret the term 'infant feeding at hospital discharge', in particular, the timeframe used to calculate these important indicators.
View Article and Find Full Text PDFBackground: Folic acid (FA) supplementation before and in early pregnancy is known to improve outcomes such as reducing neural tube defects; however, little is known about groups in Australia at risk of low FA use.
Aim: To determine whether differences exist in FA supplementation rates between Australian-born women and migrant women, with a secondary aim of examining the sociodemographic characteristics of women who are not supplementing with FA in early pregnancy.
Methods: A retrospective cohort study from January 2018-July 2022 in a high-migrant population in Western Sydney, Australia.
Gestational diabetes (GDM) is associated with a long-term risk of diabetes. We aimed to determine whether a text-messaging-based lifestyle support program would improve diabetes risk factors following GDM. Women with GDM were randomised following delivery to receive four text messages per week supporting a healthy lifestyle and parenting for 6 months, with feedback from an activity monitor (intervention), or to receive the activity monitor only (control).
View Article and Find Full Text PDFPoor bone quality is a major factor in skeletal fragility in elderly individuals. The molecular mechanisms that establish and maintain bone quality, independent of bone mass, are unknown but are thought to be primarily determined by osteocytes. We hypothesize that the age-related decline in bone quality results from the suppression of osteocyte perilacunar/canalicular remodeling (PLR), which maintains bone material properties.
View Article and Find Full Text PDFBreastfeeding is associated with reduced lifetime cardiometabolic risk, but little is known regarding the metabolic benefit in a subsequent pregnancy. The primary aim of this study was to investigate the association between breastfeeding duration and intensity and next pregnancy oral glucose tolerance test (OGTT) results. A retrospective cohort study was conducted from March 2020 to October 2022.
View Article and Find Full Text PDFCellular senescence and the senescence-associated secretory phenotype (SASP) contribute to age-related arterial dysfunction, in part, by promoting oxidative stress and inflammation, which reduce the bioavailability of the vasodilatory molecule nitric oxide (NO). In the present study, we assessed the efficacy of fisetin, a natural compound, as a senolytic to reduce vascular cell senescence and SASP factors and improve arterial function in old mice. We found that fisetin decreased cellular senescence in human endothelial cell culture.
View Article and Find Full Text PDFBrain white matter tracts undergo structural and functional changes linked to late-life cognitive decline, but the cellular and molecular contributions to their selective vulnerability are not well defined. In naturally aged mice, we demonstrate that senescent and disease-associated microglia (DAM) phenotypes converge in hippocampus-adjacent white matter. Through gold-standard gene expression and immunolabeling combined with high-dimensional spatial mapping, we identified microglial cell fates in aged white matter characterized by aberrant morphology, microenvironment reorganization, and expression of senescence and DAM markers, including galectin 3 (GAL3/), B-cell lymphoma 2 (), and cyclin dependent kinase inhibitors, including .
View Article and Find Full Text PDFObjective: This study aims to determine the effect of infant-mother separation following a short-stay (≤72 hours) admission to a Level 5 neonatal unit versus no admission on infant-feeding outcomes at hospital discharge.
Design: Retrospective cohort study.
Setting: An Australian Level 5 neonatal unit within a tertiary referral hospital.
During cellular senescence, persistent growth arrest and changes in protein expression programs are accompanied by a senescence-associated secretory phenotype (SASP). In this study, we detected the upregulation of the SASP-related protein dipeptidyl peptidase 4 (DDP4) in human primary lung cells rendered senescent by exposure to ionizing radiation. DPP4 is an exopeptidase that plays a crucial role in the cleavage of various proteins, resulting in the loss of N-terminal dipeptides and proinflammatory effects.
View Article and Find Full Text PDFBackground: Here, we assessed the role of cellular senescence and the senescence associated secretory phenotype (SASP) in age-related aortic stiffening and endothelial dysfunction.
Methods: We studied young (6-8 mo) and old (27-29 mo) p16-3MR mice, which allows for genetic-based clearance of senescent cells with ganciclovir (GCV). We also treated old C57BL/6N mice with the senolytic ABT-263.
Multiplexed antibody-based imaging enables the detailed characterization of molecular and cellular organization in tissues. Advances in the field now allow high-parameter data collection (>60 targets); however, considerable expertise and capital are needed to construct the antibody panels employed by these methods. Organ mapping antibody panels are community-validated resources that save time and money, increase reproducibility, accelerate discovery and support the construction of a Human Reference Atlas.
View Article and Find Full Text PDFBackground: As a COVID-19 risk mitigation measure, Australia closed its international borders for two years with significant socioeconomic disruption including impacting approximately 30% of the Australian population who are migrants. Migrant populations during the peripartum often rely on overseas relatives visiting for social support. High quality social support is known to lead to improved health outcomes with disruption to support a recognised health risk.
View Article and Find Full Text PDFDeveloping accurate methods to quantify age-related muscle loss (sarcopenia) could greatly accelerate development of therapies to treat muscle loss in the elderly, as current methods are inaccurate or expensive. The current gold standard method for quantifying sarcopenia is dual-energy X-ray absorptiometry (DXA) but does not measure muscle directly-it is a composite measure quantifying "lean mass" (muscle) excluding fat and bone. In humans, DXA overestimates muscle mass, which has led to erroneous conclusions about the importance of skeletal muscle in human health and disease.
View Article and Find Full Text PDFBackground: The COVID-19 pandemic has had indirect effects on pregnancy outcomes. There is limited data on the impact on gestational diabetes (GDM) in diverse populations and the possible underlying mediators. This study aimed to assess the risk of GDM pre-COVID-19 and in two distinct pandemic exposure periods, and to determine the potential factors contributing to increased risk in a multiethnic population.
View Article and Find Full Text PDFAntiretroviral drugs have dramatically improved the prognosis of HIV-infected patients, with strikingly reduced morbidity and mortality. However, long-term use can be associated with signs of premature aging. Highly active antiretroviral therapy generally comprises two nucleoside reverse transcriptase inhibitors (NRTIs), with one of three additional antiretroviral drug classes, including protease inhibitors (PIs).
View Article and Find Full Text PDFAging is accompanied by a loss of muscle mass and function, termed sarcopenia, which causes numerous morbidities and economic burdens in human populations. Mechanisms implicated in age-related sarcopenia or frailty include inflammation, muscle stem cell depletion, mitochondrial dysfunction, and loss of motor neurons, but whether there are key drivers of sarcopenia are not yet known. To gain deeper insights into age-related muscle loss, we performed transcriptome profiling on lower limb muscle biopsies from 72 young, elderly, and frail human subjects using bulk RNA-seq ( = 72) and single-nuclei RNA-seq ( = 17).
View Article and Find Full Text PDFBackground: On 9 June 2021, the Australian Technical Advisory Group on Immunisation and Royal Australian and New Zealand College of Obstetricians and Gynaecologists recommended that pregnant women receive Comirnaty (Pfizer) messenger RNA vaccine at any stage of pregnancy.
Aim: This multi-centre study aimed to assess vaccine acceptance, reasons for hesitancy and determine if differences exist between health districts, to inform future policy strategies for COVID-19 vaccination in pregnancy.
Materials And Methods: An online survey (developed based on the World Health Organization Behavioural and Social Drivers survey and modified for the pregnant population) was administered to a sample population of pregnant women attending antenatal clinics at two metropolitan hospitals (Westmead and Royal North Shore Hospital (RNSH)) in New South Wales between 15 September 2021 and 22 October 2021.
Objective: To compare birth outcomes of women with gestational diabetes mellitus (GDM) with background obstetric population, stratified by models of care.
Design: Retrospective cohort study.
Setting: A tertiary referral centre in Sydney, Australia.
Objective: In cases of suspected neonatal airway obstruction, the ex-utero intrapartum treatment (EXIT) procedure is used to secure the airway while a fetus remains on placental circulation. We report indications and outcomes from all EXIT procedures at a tertiary obstetric unit between 1997 and 2020.
Method: Retrospective cohort study with data collected from maternal and neonatal medical records.
Background: Perinatal mental health (PMH) conditions are associated with an increased risk of adverse perinatal outcomes including preterm birth. Midwifery caseload group practice (continuity of care, MCP) improves perinatal outcomes including a 24 % reduction of preterm birth. The evidence is unclear whether MCP has the same effect for women with perinatal mental health conditions.
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