Background: Posttraumatic stress disorder (PTSD) is a debilitating condition affecting millions of people worldwide. Existing treatments often fail to address the complexity of its symptoms and functional impairments resulting from severe and prolonged trauma. Electroencephalographic Neurofeedback (NFB) has emerged as a promising treatment that aims to reduce the symptoms of PTSD by modulating brain activity.

Vaccine adjuvants are thought to work by stimulating innate immunity in the draining lymph node (LN), although this has not been proven in humans. To bridge the data obtained in animals to humans, we have developed an in situ human LN explant model to investigate how adjuvants initiate immunity. Slices of explanted LNs were exposed to vaccine adjuvants and revealed responses that were not detectable in LN cell suspensions. We used this model to compare the liposome-based AS01 with its components, monophosphoryl lipid A (MPL) and QS-21, and TLR ligands. Liposomes were predominantly taken up by subcapsular sinus–lining macrophages, monocytes, and DCs. AS01 induced DC maturation and a strong proinflammatory cytokine response in intact LN slices but not in dissociated cell cultures, in contrast to R848. This suggests that the onset of the immune response to AS01 required a coordinated activation of LN cells in time and space. Consistent with the robust immune response observed in older adults with AS01-adjuvanted vaccines, the AS01 response in human LNs was independent of age, unlike the response to R848. This human LN explant model is a valuable tool for studying the mechanism of action of adjuvants in humans and for screening new formulations to streamline vaccine development.

Background: 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. Methods: A multicentre, retrospective cohort study was performed of women with singleton pregnancy receiving antenatal care at three hospitals two years pre-COVID-19 (January 2018 – January 2020), first year of COVID-19 with limited pandemic-mitigating restrictions (February 2020 – January 2021) and second year of COVID-19 with stringent restrictions (February 2021 – January 2022). Baseline maternal characteristics and gestational weight gain (GWG) were compared between cohorts. The primary outcome was GDM, assessed using univariate and multivariate generalised estimating equations models. Results: 28,207 pregnancies met the inclusion criteria, 14,663 pregnancies two years pre-COVID-19, 6,890 in COVID-19 Year 1 and 6,654 in COVID-19 Year 2. Maternal age increased across exposure periods (30.7 ± 5.0 years pre-COVID-19 vs 31.0 ± 5.0 years COVID-19 Year 1 vs 31.3 ± 5 years COVID-19 Year 2; p < 0.001). There were increases in pre-pregnancy body mass index (BMI) (25.5 ± 5.7 kg/m² vs 25.7 ± 5.6 kg/m² vs 26.1 ± 5.7 kg/m²; p < 0.001), proportion who were obese (17.5% vs 18.1% vs 20.7%; p < 0.001) and proportion with other traditional risk factors for GDM including South Asian ethnicity and prior history of GDM. Rate of GWG and proportion exceeding recommended GWG increased with pandemic exposure (64.3% vs 66.0% vs 66.6%; p = 0.009). GDM diagnosis increased across exposure periods (21.2% vs 22.9% vs 24.8%; p < 0.001). Both pandemic exposure periods were associated with increased risk of GDM on univariate analysis, only COVID-19 Year 2 remaining significantly associated after adjusting for maternal baseline characteristics and GWG (OR 1.17 [1.06, 1.28], p = 0.01). Conclusions: Diagnosis of GDM increased with pandemic exposure. Progressive sociodemographic changes and greater GWG may have contributed to increased risk. However, exposure to the second year of COVID-19 remained independently associated with GDM after adjusting for shifts in maternal characteristics and GWG.

Introduction Novel strategies are needed to address the rising burden of osteoporosis and fragility fractures. High-intensity resistance and impact (HiRIT) exercise has shown benefit in improving bone density in postmenopausal women with osteoporosis/osteopenia. Whether HiRIT can enhance the therapeutic effects of osteoporosis pharmacotherapy has not been established. ROLEX-DUO is a randomised controlled trial designed to assess the efficacy of romosozumab on various bone and muscle outcomes in combination with different exercise interventions in women with postmenopausal osteoporosis/osteopenia. Methods and analysis ROLEX-DUO is an 8-month randomised placebo-controlled trial conducted at two tertiary referral centres for patients with osteoporosis/osteopenia in Sydney, New South Wales, Australia. The study is implementing the combination of romosozumab or placebo with different forms of exercise in postmenopausal women with osteoporosis/osteopenia without recent fragility fracture (n=102). Eligible women will be randomised 1:1:1 into one of three groups: (1) romosozumab with supervised HiRIT, (2) romosozumab with unsupervised low-intensity exercise or (3) placebo with unsupervised low-intensity exercise. Co-primary outcomes are the mean percentage change in lumbar spine bone mineral density (BMD), and mean change in five times sit-to-stand test performance (seconds) at 8 months. Secondary/exploratory outcomes include BMD changes at the femoral neck, total hip and distal radius, three-dimensional dual-energy X-ray absorptiometry (DXA) hip outcomes, DXA-derived lean and fat mass, serum markers of bone turnover (procollagen type 1 peptide, C-telopeptide of type 1 collagen) and bone biomarkers (dickkopf-1), serum extracellular vesicle analyses, 36-Item Short Form Survey (SF-36) quality-of-life scores, Menopause-Specific Quality Of Life (MENQOL) Questionnaire menopause symptom burden scores, number of falls and fractures. Mixed-effects models will be performed to compare longitudinal outcome results between groups using intention-to-treat analysis. Ethics and dissemination The trial was approved by the Northern Sydney Local Health District Human Research Ethics Committee (2022/ETH01794, protocol V.8, dated 03 July 2024). Participants will provide written informed consent prior to inclusion. Findings will be disseminated via peer-reviewed journals, scientific conferences and summary reports to funding bodies. Trial registration number ACTRN12623000867695.

Introduction: The demographic shift amongst pregnant women, including older age and increasing obesity, has resulted in an increased risk of cardiometabolic complications during pregnancy, particularly gestational diabetes. This paper presents physical activity and gestational diabetes data in a multi-ethnic urban Australian population. Methods and analysis: The PROMOTE cohort study is an ongoing prospective pregnancy cohort study recruiting pregnant participants < 16 weeks gestation at a large urban public teaching hospital with high social and cultural diversity in Sydney, Australia. Participants are surveyed about their physical activity levels, dietary quality, emotional wellbeing and socio-demographic status using validated tools. Participants are consented for use of routinely collected clinical and social data, including medical conditions, body mass index (BMI), blood pressure (BP) and glycaemia. Follow-up is from routinely collected data. Results: A total of 459 participants were recruited between February 2022 and February 2024. Physical activity levels at recruitment were sufficiently active, low active and inactive in 39%, 45% and 16% of participants. Participation in moderate or vigorous physical activity was reported in 19% and 16% of participants, respectively. Participation in vigorous physical activity occurred in 10% of those with GDM vs. 17% of those without GDM (p = 0.11). Participation in any moderate/vigorous physical activity was reported in 20% of those with GDM vs. 30% of those without GDM (p = 0.058). Compared to inactive behaviour, the unadjusted odds ratio of developing GDM amongst those participating in any moderate/vigorous physical activity was 0.58 (95% CI 0.33–0.97), p = 0.045. Participation in any moderate/vigorous physical activity showed an association with lower oral glucose tolerance test levels at 1 h (7.49 vs. 8.17 mmol/L, p = 0.002). Participation in any vigorous activity was associated with lower oral glucose tolerance test levels at 1 h (7.25 vs. 8.11, p = <0.001). Conclusions: Uptake of existing physical activity recommendations is low. Gestational diabetes risk showed a trend toward variation by intensity of physical activity, with a trend toward greater intensity being associated with a possible lower rate of gestational diabetes.