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Breastfeeding 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. All multiparous women who met inclusion criteria and gave birth during the study period were eligible for inclusion. Analysis was stratified by risk for gestational diabetes (GDM). High GDM risk criteria included previous GDM and BMI > 35 kg/m2. The association between breastfeeding duration and high-intensity breastfeeding (HIBF) and subsequent pregnancy OGTT were assessed with multivariate logistic models adjusted for statistically and clinically relevant covariables. There were 5374 multiparous participants who met the inclusion criteria for analysis. Of these, 61.7% had previously breastfed for >6 months, and 43.4% were at high risk for GDM. HIBF was associated with 47% reduced odds of an abnormal fasting glucose in a subsequent pregnancy OGTT (aOR 0.53; 95%CI 0.38–0.75; p < 0.01). There was no association between HIBF and other glucose results on the OGTT. Women who smoked were least likely to breastfeed at high intensity (aOR 0.31; 95%CI 0.21–0.47; p < 0.01). South Asian women had 65% higher odds of HIBF than women who identified as White/European (aOR 1.65; 1.36–2.00; p < 0.01). This study highlights the importance of exclusive breastfeeding to potentially reduce the prevalence of GDM and may also translate into long-term reduction of cardiometabolic risk. [ABSTRACT FROM AUTHOR]

Large (≥20 mm) nonpedunculated colorectal polyps (LNPCPs) may have synchronous LNPCPs in up to 18% of cases. The nature of this relationship has not been investigated. We aimed to examine the relationship between individual LNPCP characteristics and synchronous colonic LNPCPs. Consecutive patients referred for resection of LNPCPs over 130 months until March 2022 were enrolled. Serrated lesions and mixed granularity LNPCPs were excluded from analysis. Patients with multiple LNPCPs resected were identified, and the largest was labelled as dominant. The primary outcome was the identification of individual lesion characteristics associated with the presence of synchronous LNPCPs. There were 3149 of 3381 patients (93.1%) who had a single LNPCP. In 232 (6.9%) a synchronous lesion was detected. Solitary lesions had a median size of 35 mm with a predominant Paris 0-IIa morphology (42.9%) and right colon location (59.5%). In patients with ≥2 LNPCPs, the dominant lesion had a median size of 40 mm, Paris 0-IIa (47.6%) morphology, and right colon location (65.9%). In this group, 35.8% of dominant LNPCPs were non-granular compared with 18.7% in the solitary LNPCP cohort. Non-granular (NG)-LNPCPs were more likely to demonstrate synchronous disease, with left colon NG-LNPCPs demonstrating greater risk (odds ratio, 4.78; 95% confidence interval, 2.95–7.73) than right colon NG-LNPCPs (odds ratio, 1.99; 95% confidence interval, 1.39–2.86). We found that 6.9% of LNPCPs have synchronous disease, with NG-LNPCPs demonstrating a greater than 4-fold increased risk. With post-colonoscopy interval cancers exceeding 5%, endoscopists must be cognizant of an individual's LNPCP phenotype when examining the colon at both index procedure and surveillance. ClinicalTrials.gov , NCT01368289; NCT02000141; NCT02198729. [ABSTRACT FROM AUTHOR]

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.

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., Competing Interests: Competing interests: All authors have completed the ICMJE uniform disclosure form at http://www.icmje.org/disclosure-of-interest/ and declare: all authors had financial support from Healthy Bones Australia, Australian New Zealand Bone and Mineral Society, Avant Mutual and NORTH Foundation for grant funding for the submitted work. Belinda R Beck is owner and director of The Bone Clinic (TBC) which is the licensee of the HiRIT programme being used in this study. All other authors declare no financial relationships with any organisations that might have an interest in the submitted work in the previous three years and no other relationships or activities that could appear to have influenced the submitted work., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)