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BACKGROUND: Limited data are available on vitamin A kinetics and total body stores (TBS) in women. Such information can be obtained using compartmental modeling and retinol isotope dilution (RID). OBJECTIVES: Objectives were to apply population-based (super-subject) modeling to determine retinol kinetics in nonpregnant Ghanaian women of reproductive age and to use RID to predict TBS in the group and its individuals. METHODS: Women (n = 89) ingested a dose of [2H6]retinyl acetate and blood samples (3/woman) were collected from 6 h to 91 d, with all participants sampled at 14 d, about half at either 21 or 28 d, and each at one other time. Composite data (plasma retinol fraction of dose; FDp) were analyzed using Simulation, Analysis and Modeling software to obtain kinetic parameters, TBS, and other state variables as well as model-derived values for the RID composite coefficient FaS. The latter were used in the RID equation TBS (μmol) = FaS × 1/SAp (where SAp is plasma retinol specific activity) to predict TBS at various times. RESULTS: Model-predicted TBS was 973 μmol (n = 87). Geometric mean RID-predicted TBS was 965, 926, and 1006 μmol at 14, 21, and 28 d, respectively, with wide ranges [for example, 252-3848 μmol on day 14 (n = 86)]; TBS predictions were similar at later times. Participants had a mean 2 y of vitamin A in stores and estimated liver vitamin A concentrations in the normal range. Model-predicted vitamin A disposal rate was 1.3 μmol/d and plasma recycling number was 37. CONCLUSIONS: Super-subject modeling provides an estimate of group mean TBS as well as group-specific values for the RID coefficient FaS; the latter can be used to confidently predict TBS by RID for individual participants in the group under study or in similar individuals at 14 d or more after isotope ingestion. TRIAL REGISTRATION NUMBER: Trial is registered (NCT04632771) at https://clinicaltrials.gov.

Given the recruitment and retention crisis within the teaching profession, it is essential that the factors contributing to this are examined. Studies suggest that there has been a general decline in teacher wellbeing since the onset of the COVID-19 pandemic, and student conduct problems are known to be a key negative contributor to poor teacher wellbeing. This study examines how student conduct problems influenced teachers' wellbeing following the onset of the COVID-19 pandemic. Specifically, it explores the extent to which student behaviour was seen as changing during the pandemic, and how this may have had an impact on teachers' wellbeing. Nine participants took part in this study. All the participants were teachers in schools in England (four primary and five secondary; nine female). The data were collected via semi-structured virtual interviews. Using a qualitative approach, the study undertook an in-depth analysis of the interview data using Interpretative Phenomenological Analysis. The findings suggest that the teachers experienced an increase in student conduct problems following the onset of the pandemic and that this negatively affected wellbeing for some. The teachers also reported an increased need for student support and differential needs for different groups of students. It is important that consideration is given as to how teachers can be effectively supported to manage student conduct problems and the potential impact of these on their wellbeing, particularly since the onset of the pandemic.

In societies where authoritarian and populist perspectives are on the rise, a focus on the concept of democracy within education can provide a meaningful space to reflect critically on, and disrupt, the status quo. In post-dictatorship Portugal, democracy has become a central symbolic concept within education policy and, in particular, Early Childhood Education (ECE) policy emphasises the importance of democratic citizenship within children's personal and social development. Through a lens of critical pedagogy, we examine the diverse enactments of democracy at the classroom level within ECE settings in Portugal. By analysing interviews with twenty early years educators in three kindergartens, we identified ten concepts of democratic educational practice. Through observation of their classrooms, we explored divergent applications of these concepts in practice which embodied three distinct pedagogical approaches, which we termed instructive, responsive, and synergetic. These respectively enacted three styles of classroom democracy, which we described as procedural, interactive and critical democracy. We found that "critical democracy" was most evident where collaborative democratic spaces were created by educators who emphasised and enacted the values of listening, critical thinking, freedom, and respect.

Introduction The number of patients desiring fertility-preserving treatment for endometrial cancer rather than standard surgical management continues to increase.Objective We aimed to evaluate the efficacies of fertility-preserving treatments on the live birth rate, remission and relapse rates for women with stage 1a grade 1 endometrial carcinoma to support patient counselling.Methods We performed a meta-analysis for our primary outcomes of overall remission and relapse rate, and for secondary analysis, we divided papers into treatment type: systemic progestins, intrauterine progestins or hysteroscopic resection and adjuvant hormonal treatment.Results Thirty-five observational studies met inclusion criteria, with a total of 624 patients. Overall, conservative treatment of endometrial cancer showed a remission rate of 77% (95% CI: 70–84%), a relapse rate of 20% (95% CI: 13–27%) and a live birth rate of 20% (95% CI: 15–25%) with more favourable outcomes for the hysteroscopic resection group.Conclusions Hysteroscopic resection and adjuvant hormonal treatment had the most favourable fertility and oncological outcomes. Further high-quality prospective multi-centre trials are warranted to determine the optimal treatment regimen and dosage and risk stratification for these patients.

Background: Limited data are available on vitamin A kinetics and total body stores (TBS) in women. Such information can be obtained using compartmental modeling and retinol isotope dilution (RID). Objectives: Objectives were to apply population-based (“super-subject”) modeling to determine retinol kinetics in nonpregnant Ghanaian women of reproductive age and to use RID to predict TBS in the group and its individuals. Methods: Women (n = 89) ingested a dose of [2H6]retinyl acetate and blood samples (3/woman) were collected from 6 h to 91 d, with all participants sampled at 14 d, about half at either 21 or 28 d, and each at one other time. Composite data (plasma retinol fraction of dose; FDp) were analyzed using Simulation, Analysis and Modeling software to obtain kinetic parameters, TBS, and other state variables as well as model-derived values for the RID composite coefficient FaS. The latter were used in the RID equation TBS (μmol) = FaS × 1/SAp (where SAp is plasma retinol specific activity) to predict TBS at various times. Results: Model-predicted TBS was 973 μmol (n = 87). Geometric mean RID-predicted TBS was 965, 926, and 1006 μmol at 14, 21, and 28 d, respectively, with wide ranges [for example, 252–3848 μmol on day 14 (n = 86)]; TBS predictions were similar at later times. Participants had a mean 2 y of vitamin A in stores and estimated liver vitamin A concentrations in the normal range. Model-predicted vitamin A disposal rate was 1.3 μmol/d and plasma recycling number was 37. Conclusions: Super-subject modeling provides an estimate of group mean TBS as well as group-specific values for the RID coefficient FaS; the latter can be used to confidently predict TBS by RID for individual participants in the group under study or in similar individuals at 14 d or more after isotope ingestion. Trial registration number: Trial is registered (NCT04632771) at https://clinicaltrials.gov.

Introduction: Reactive angioendotheliomatosis (RAE) is a rare, benign, angioproliferative disorder with poorly understood aetiopathogenesis. It is characterised by vascular occlusion that occurs in patients with coexistent systemic or autoimmune disease. Case Presentation: A 60-year-old female presented with an 8-week history of a painful, non-healing, and non-traumatic ulcer on the left thigh. Her past medical history included smoking, peripheral vascular disease (PVD) and previously treated rectal squamous cell carcinoma. The diagnosis of pyoderma gangrenosum with superimposed cellulitis was considered and treatment with oral antibiotics was initiated. Following failure to improve, a biopsy was undertaken leading to the diagnosis of RAE. The patient was referred for urgent consideration of surgical correction of PVD, but was deemed unsuitable for surgical treatment due to a poor performance status. The patient was treated with conservative measures, but her condition rapidly deteriorated and she passed away a few weeks later. Conclusion: RAE is notorious for mimicking a wide spectrum of diseases. It is an important differential diagnosis to consider in patients with non-healing ulceration and underlying systemic or autoimmune disorders. Our case raises awareness of this rare condition and the mortality that it carries if left untreated. In an attempt to reverse disease progression and mortality, we urge clinicians to attempt surgical correction of PVD even when faced with multiple comorbidities and poor performance status.

It is known that social support is one of the main protective factors in the postpartum period. In addition, studies report the association between biological rhythm disruption and its consequences on health, especially mental, but little is known about the possible causes of this disruption. Thus, the objective of this study was to evaluate the association between the perception of social support and the biological rhythm in women at three months postpartum in the city of Pelotas, Brazil. This is a cross-sectional study nested within a population-based cohort study, using data from an assessment performed 90 to 120 days postpartum. The mother's perception of social support was assessed by the Medical Outcomes Study Social Support Scale (MOS-SSS), while biological rhythm was measured by the Biological Rhythms Interview of Assessment in Neuropsychiatry (BRIAN). Sample composition was based on data from 755 women. After adjusting by linear regression for the potential confounders of schooling and economic class, all domains of social support (material support, affective support, emotional support, informational support and positive social interaction) remained negatively associated with biological rhythm (p < .001). Thus, regression analysis shows for each increment of one point in the domains of social support, there was a decrease between 0,160 and 0,189 points in the maternal biological rhythm. All domains of social support were associated with disruption of the biological rhythm, which reinforces the need for adequate support, especially in a period of many demands, for good maternal health.

Summary: T cell surface CTLA4 sequesters the costimulatory ligands CD80 and CD86 on antigen-presenting cells (APCs) to prevent autoimmunity. Therapeutic immunosuppression by recombinant CTLA4-immunoglobulin (Ig) fusion proteins, including abatacept, is also attributed to CD80/CD86 blockade. Recent studies show that CTLA4-Ig binding to APC surface cis-CD80:PD-L1 complexes can release the inhibitory ligand PD-L1, but whether this contributes to T cell inhibition remains unclear. Here, we show that PD-L1 liberation by CTLA4-Ig is strictly limited, both in extent and context, relative to PD-L1-competing anti-CD80 antibodies. At APC surface CD80:PD-L1 ratios exceeding 2:1, CTLA4-Ig therapies fail to release PD-L1 regardless of their CD80 affinity. Additionally, introducing flexibility into CTLA4-Ig by modifying its rigid homodimer interface produces biologics that retain bivalent CD80 binding without dissociating cis-bound PD-L1. These findings demonstrate that CTLA4-Ig therapies liberate PD-L1 through a CD80 reorientation mechanism that imposes a strict context dependence to their PD-1 checkpoint agonism and resultant T cell inhibition.

The Safe System approach is a commonly adopted approach internationally to address road traffic injuries. Existing research has identified that the approach has multiple descriptions, and there have been noted difficulties associated with implementation. Practitioners have an important role in rolling out road safety interventions, and thus are a key point for translating Safe System into practice. However, there has been limited investigation of how practitioners view and understand Safe System. Of particular importance is practitioners' interpretation of Safe System's purpose and the facilitators and barriers to application. Four hundred and sixty-nine respondents completed an online survey which investigated perceptions regarding Safe System's purpose.The results highlight that practitioners view Safe System as being multidimensional, with a range of ideas about what the overall purpose is. Safe System was perceived as both visionary and practical, with the majority of respondents reporting that it defines a broad outcome for road safety and provides direction on how to respond to road traffic injury. Additionally, two thirds of respondents identified that they applied Safe System to the last project or program they worked on and were broadly supportive of the approach. However, multiple impediments to application were identified, with these barriers effected by the practitioners' demographics, role and organisation. For practitioners, Safe System represents a complex approach that aims to reduce injury and deaths, however, effective application can only occur when barriers are reduced.

BackgroundYoung children exposed to high-dose vitamin A supplements (VAS) and vitamin A (VA)-fortified foods may be at risk of high VA intake and high VA total body stores (TBS).ObjectivesTBS and estimated liver VA concentration were compared among children with adequate or high VA intake and different timing of exposure to VAS, and associations between estimated liver VA concentrations and biomarkers of VA toxicity were examined.MethodsChildren 12-18 mo of age (n = 123) were selected for 3 groups: 1) retinol intake >600 µg/d and VAS within the past mo, 2) retinol intake >600 µg/d and VAS in the past 3-6 mo, and 3) VA intake 200-500 µg retinol activity equivalents (RAE)/d and VAS in the past 3-6 mo. Dietary intake data were collected to measure VA intakes from complementary foods, breast milk, and low-dose, over-the-counter supplements. TBS were assessed by retinol isotope dilution, and VA toxicity biomarkers were measured. Main outcomes were compared by group.ResultsMean (95% CI) VA intakes excluding VAS were 1184 (942, 1426), 980 (772, 1187), and 627 (530, 724) µg RAE/d, in groups 1-3, respectively; mean VA intake was higher in groups 1 and 2 compared with group 3 (P 1 µmol/g liver). There was no evidence of chronic VA toxicity, suggesting that the liver VA cutoff value should be re-evaluated. This trial was registered at www.clinicaltrials.gov as NCT03030339.