Many Australian adults with type 2 diabetes mellitus (T2DM) do not follow recommended self-management behaviours that could prevent or delay complications. This exploratory study aimed to investigate the factors influencing self-management of T2DM in general practice. Semi-structured qualitative interviews were conducted with patients with T2DM (n = 10) and their GPs (n = 4) and practice nurses (n = 3) in a low socioeconomic area of Sydney, New South Wales, Australia. The interviews were analysed thematically using the socio-ecological model as a framework for coding. Additional themes were derived inductively based on the explicitly stated meaning of the text. Factors influencing self-management occurred on four levels of the socio-ecological model: individual (e-health literacy, motivation, time constraints); interpersonal (family and friends, T2DM education, patient-provider relationship); organisational (affordability, multidisciplinary care); and community levels (culture, self-management resources). Multi-level strategies are needed to address this wide range of factors that are beyond the scope of single services or organisations. These could include tailoring health education and resources to e-health literacy and culture; attention to social networks and the patient–provider relationship; and facilitating access to affordable on-site allied health services.

Pharmacological manipulations in the Drosophila embryo have been hindered by the impermeability of the eggshell. The ultimate barrier to delivery of small molecule solutes to the embryo is the waxy layer that lies beneath the external chorion layers and encases the underlying vitelline membrane of the eggshell. Conventional protocols call for heptane or octane to permeablize the dechorionated eggshell however, these solvents are toxic and can result in low viability. Furthermore, heptane and octane require transition of the embryo between aqueous and organic phase solvents making it challenging to avoid desiccation. Here we describe an embryo permeabilization solvent (EPS) composed of D-limonene and plant-derived surfactants that is water miscible and highly effective in rendering the dechorionated eggshell permeable. EPS permeabilization enables embryo uptake of several different dyes of various molecular mass up to 995 Daltons. We find that the embryo undergoes an age dependent decrease in the ability to be permeabilized in the first six to eight hours after egg laying. This apparent developmental change in the vitelline membrane contributes to the heterogeneity in permeabilization seen even among closely staged embryos. However, using fluorescent properties of Rhodamine B dye and various conditions of EPS treatment we demonstrate the ability to obtain optimally permeabilized viable embryos. We also demonstrate the ability to assess teratogenic activity of several compounds applied to embryos in vitro, using both early and late developmental endpoints. Application of the method to transgenic strains carrying GFP reporter genes results in a robust readout of pharmacological alteration of embryogenesis. The straightforward and rapid nature of the manipulations needed to prepare batches of permeabilized embryos has the potential of establishing the Drosophila embryo as an alternative model in toxicology and for small molecule screening in a high throughput format.

Methylmercury (MeHg) is a potent environmental neurotoxin that preferentially targets the developing embryonic nervous system. While a number of cytotoxic mechanisms of MeHg have been characterized in differentiated cells its mode of action in the developing nervous system in vivo is less clear. Studies in primate and rodent models demonstrate aberrant cell migration and disorganized patterning of cortical layers in the brain following MeHg exposure. However, defining the molecular and cellular pathways targeted by MeHg will require more genetically accessible animal models. In this study, we instigate a method of in vitro MeHg exposure using Drosophila embryos. We demonstrate dose-dependent inhibition of embryonic development with MeHg revealed by a failure of embryos to hatch to the larval stage. In addition, we document definitive phenotypes in neural development showing abnormalities in neuronal and glial cell patterning consistent with disrupted migration. As well, we observe pronounced defects in neurite outgrowth in both central and peripheral neurons. Ectopic expression of the Nrf2 transcription factor in embryos, a core factor in the antioxidant response element (ARE) pathway, enhances embryonic development and hatching in the presence of MeHg, illustrating the power of this model for investigation of candidate MeHg tolerance genes. Our data establish a utility for the Drosophila embryo model as a platform for elucidating MeHg sensitive pathways in neural development.

An evidence-based systematic review of kratom (Mitragyna speciosa) by the Natural Standard Research Collaboration consolidates the safety and efficacy data available in the scientific literature using a validated, reproducible grading rationale. This article includes written and statistical analysis of clinical trials, plus a compilation of expert opinion, folkloric precedent, history, pharmacology, kinetics/dynamics, interactions, adverse effects, toxicology, and dosing.

Acute myeloid leukaemia (AML) requires intensive chemotherapy for cure. Regimens from the Children's Oncology Group (COG) represent the most common treatment approach to paediatric AML in North America. These regimens utilize up to five cycles of intensive chemotherapy, with a high anthracycline burden (~492-684 mg/m 2 doxorubicin equivalents), 1 contributing to acute morbidity and long-term cardiotoxicity. 2 The United Kingdom Medical Research Council (MRC) AML 15 randomized trial tested a new double induction regimen of fludarabine, high-dose cytarabine (HDAc), G-colony stimulating factor (GCSF) and idarubicin (FLAG-IDA) in adults and a small subset of paediatric patients. 3 MRC 15 included four cycles of chemotherapy with lower intensity and less anthracycline exposure (cumulatively, ~240 mg/m 2 doxorubicin equivalents), and demonstrated excellent survival. 3 As a result, we adopted MRC-15-based therapy as routine care. Between 2014 and 2021, we treated 30 patients with de novo AML (Table 1) and describe here disease response, morbidity and survival. Each case was characterized by cytogenetics, chromosomal microarray and a proprietary molecular testing panel (OncoKids®). 4 Treatment was delivered per MRC 15, 5 adapted to reflect institutional standard of care. Briefly, patients received double induction chemotherapy (fludarabine 30 mg/m 2 and cytarabine 2 g/m 2 IV days 2-6, idarubicin 8 mg/m 2 IV days 4-6, GCSF 5 mcg/kg days 1-7 [optionally omitted for patients with leukocytosis]) followed by double consolidation (cytarabine 3 g/m 2 q12 hours days 1,3,5). Following regulatory approval in 2017, patients with CD33+ received gemtuzumab ozogamicin (GO, 3 mg/m 2 IV day 7, maximum dose 4.5 mg) as per treating physician discretion. Tyrosine kinase inhibitors (TKI) were optionally included for patients with FLT3 mutations. Disease response was assessed by flow-cytometric minimal residual disease (MRD) following Induction I (and II, if positive) using a 'difference from normal' approach. 6 MRD+ was defined using COG threshold at the time of treatment (≥0.1%). 7 Final risk category was assigned from presenting molecular analyses and post-Induction I MRD using COG classification at the time of diagnosis (per AAML1031 or AAML1831) (Table S1).