Ubiquitin-mediated recruitment of the ATG9A-ATG2 lipid transfer complex drives clearance of phosphorylated p62 aggregates.

Autophagy is an essential cellular recycling process that maintains protein and organelle homeostasis. ATG9A vesicle recruitment is a critical early step in autophagy to initiate autophagosome biogenesis. The mechanisms of ATG9A vesicle recruitment are best understood in the context of starvation-induced non-selective autophagy, whereas less is known about the signals driving ATG9A vesicle recruitment to autophagy initiation sites in the absence of nutrient stress.

Intradermal electrical stimulation of sudomotor nerves and local sweat rate.

The local sweat rate (LSR) response to intradermal electrical stimulation generates a sigmodal stimulus-response curve with a peak sweat rate generated during a 30-s period of continuous stimuli at a frequency of 16-32 Hz. However, the in vivo firing pattern of the sudomotor nerve resembles more of a bursting pattern. We tested the hypothesis that a bursting pattern during intradermal electrical stimulation would result in a greater sweating response than the regular continuous stimulus pattern.

Development of a cross-sectoral antimicrobial resistance capability assessment framework.

Antimicrobial resistance (AMR) is an urgent and growing global health concern, and a clear understanding of existing capacities to address AMR, particularly in low-income and middle-income countries (LMICs), is needed to inform national priorities, investment targets and development activities. Across LMICs, there are limited data regarding existing mechanisms to address AMR, including national AMR policies, current infection prevention and antimicrobial prescribing practices, antimicrobial use in animals, and microbiological testing capacity for AMR. Despite the development of numerous individual tools designed to inform policy formulation and implementation or surveillance interventions to address AMR, there is an unmet need for easy-to-use instruments that together provide a detailed overview of AMR policy, practice and capacity.

The formation of ubiquitin rich condensates triggers recruitment of the ATG9A lipid transfer complex to initiate basal autophagy.

Autophagy is an essential cellular recycling process that maintains protein and organelle homeostasis. ATG9A vesicle recruitment is a critical early step in autophagy to initiate autophagosome biogenesis. The mechanisms of ATG9A vesicle recruitment are best understood in the context of starvation-induced non-selective autophagy, whereas less is known about the signals driving ATG9A vesicle recruitment to autophagy initiation sites in the absence of nutrient stress.

Delabeling, safety, and impact of β-lactam allergy testing: A systematic review.

Background: To improve β-lactam delabeling outcomes, we need to understand current practice and the evidence base regarding its outcomes, safety, and impact.

Objectives: We sought to assess the existing published evidence reporting on the effectiveness of penicillin allergy testing and delabeling.

Methods: We conducted a systematic review of studies reporting β-lactam delabeling practices and outcomes after testing, including β-lactam use and patient understanding of the delabeling result.

Single center evaluation on the use of conditionally ordered low molecular weight heparins in malignant hematology patients with venous thromboembolism.

Background: Cancer and cancer-related treatments are significant independent risk factors for malignant hematology (MH) patients in developing venous thromboembolism (VTE). Treatment of VTE in MH patients at the Princess Margaret Cancer Centre is predominantly initiated with low molecular weight heparin (LMWH) in accordance with guidelines. While guidelines recommend against LMWH use in patients with thrombocytopenia, prescribers may order LMWH conditionally based on platelet values.

Predictors of severe and recurrent adult anaphylaxis, and gaps in the cascade of care: a retrospective, single-centre study 2009-2018.

Background: Anaphylaxis is a severe, potentially fatal, systemic allergic reaction. Understanding predictors of recurrent and severe anaphylaxis in adults, and identifying gaps in ongoing anaphylaxis care, is needed to minimise its impact.

Aims: To evaluate the risk factors in adults with severe and recurrent anaphylaxis presentations and to evaluate the management of patients in regard to the recommended cascade of care.

The implications of defining obesity as a disease: a report from the Association for the Study of Obesity 2021 annual conference.

Unlike various countries and organisations, including the World Health Organisation and the European Parliament, the United Kingdom does not formally recognise obesity as a disease. This report presents the discussion on the potential impact of defining obesity as a disease on the patient, the healthcare system, the economy, and the wider society. A group of speakers from a wide range of disciplines came together to debate the topic bringing their knowledge and expertise from backgrounds in medicine, psychology, economics, and politics as well as the experience of people living with obesity.

Public-making in a pandemic: The role of street art in East African countries.

Street artists around the world have been prominent in depicting issues concerning COVID-19, but the role of street art in public-making during the pandemic is unexplored. Despite burgeoning street art scenes in many African countries since the early 2000s, African street art is relatively neglected in critical street art scholarship. In response, this paper examines street art created during the pandemic in East African countries, principally Uganda, Kenya, Rwanda, and Tanzania, and explores the ways in which it is engaged in highly distinctive forms of public-making.

BioID reveals an ATG9A interaction with ATG13-ATG101 in the degradation of p62/SQSTM1-ubiquitin clusters.

ATG9A, the only multi-pass transmembrane protein among core ATG proteins, is an essential regulator of autophagy, yet its regulatory mechanisms and network of interactions are poorly understood. Through quantitative BioID proteomics, we identify a network of ATG9A interactions that includes members of the ULK1 complex and regulators of membrane fusion and vesicle trafficking, including the TRAPP, EARP, GARP, exocyst, AP-1, and AP-4 complexes. These interactions mark pathways of ATG9A trafficking through ER, Golgi, and endosomal systems.

Benefits of medicines optimisation for older people living with frailty.

Medicines optimisation involves ensuring that medicines are administered safely and effectively. In the UK, an ageing population and an increasing prevalence of polypharmacy mean that interprofessional medicines reviews and medicines optimisation are vital. This article uses a case study of an older person living with frailty to provide a critical analysis of the medicines optimisation process in optimising health outcomes.

A community-based co-designed genetic health service model for Aboriginal Australians.

Background: Aboriginal and Torres Strait Islander people experience a greater burden of disease and die younger than non-Indigenous Australians, with Aboriginal people living in remote areas of the Northern Territory of Australia having the lowest life expectancy estimates. Despite a high burden of chronic disease among Aboriginal and Torres Strait Islander people, access to specialist health services remains low and models of care that increase engagement, may improve health outcomes.

Methods: We describe client and staff perspectives of a model of clinical genetics services provided by the MJD Foundation (MJDF) in geographically and culturally complex contexts within the Northern Territory of Australia.

A cost-effectiveness analysis of genomic sequencing in a prospective versus historical cohort of complex pediatric patients.

Purpose: Cost-effectiveness evaluations of first-line genomic sequencing (GS) in the diagnosis of children with genetic conditions are limited by the lack of well-defined comparative cohorts. We sought to evaluate the cost-effectiveness of early GS in pediatric patients with complex monogenic conditions compared with a matched historical cohort.

Methods: Data, including investigation costs, were collected in a prospective cohort of 92 pediatric patients undergoing singleton GS over an 18-month period (2016-2017) with two of the following: a condition with high mortality, multisystem disease involving three or more organs, or severe limitation of daily function.

National Referral Prioritization tool for first specialist assessment: results of a pilot study in orthopaedic surgery.

Background: Most public hospitals are receiving more referrals for first specialist assessment than they have capacity to see. Traditional priority categories are too broad for effective discrimination. In New Zealand (NZ) explicit prioritization is required by legislation and supported by the Medical Council of NZ.

Australia's overseas development aid commitment to health through the sustainable development goals: a multi-stakeholder perspective.

Background: In 2018, the Australian Government, through a Senate-led Parliamentary Inquiry, sought the views of diverse stakeholders on Sustainable Development Goal (SDG) implementation both domestically and as part of Australia's Overseas Development Assistance (ODA) program. One hundred and sixty-four written submissions were received. The submissions offered perspective and guidance from a rich cross-section of those involved, and with keen interest in, Australia's ODA-SDG commitment.

Proteomic Analysis of Resistance of Gram-Negative Bacteria to Chlorhexidine and Impacts on Susceptibility to Colistin, Antimicrobial Peptides, and Ceragenins.

Use of chlorhexidine in clinical settings has led to concerns that repeated exposure of bacteria to sub-lethal doses of chlorhexidine might result in chlorhexidine resistance and cross resistance with other cationic antimicrobials including colistin, endogenous antimicrobial peptides (AMPs) and their mimics, ceragenins. We have previously shown that colistin-resistant Gram-negative bacteria remain susceptible to AMPs and ceragenins. Here, we investigated the potential for cross resistance between chlorhexidine, colistin, AMPs and ceragenins by serial exposure of standard strains of Gram-negative bacteria to chlorhexidine to generate resistant populations of organisms.

Reducing Tumour Hypoxia via Oral Administration of Oxygen Nanobubbles.

Hypoxia has been shown to be a key factor inhibiting the successful treatment of solid tumours. Existing strategies for reducing hypoxia, however, have shown limited efficacy and/or adverse side effects. The aim of this study was to investigate the potential for reducing tumour hypoxia using an orally delivered suspension of surfactant-stabilised oxygen nanobubbles.

A versatile, stimulus-responsive nanoparticle-based platform for use in both sonodynamic and photodynamic cancer therapy.

Unlabelled: A PLGA-based multifunctional biodegradable nanoparticle platform co-harboring hematoporphyrin and indocyanine green has been developed. In vitro studies demonstrate ultrasound and light stimulated generation of cytotoxic reactive oxygen species. In vivo studies show that the ICG component facilitates nIR fluorescence imaging that demonstrates accumulation of IV- administered nanoparticles in tumours.

A Christianson syndrome-linked deletion mutation (∆(287)ES(288)) in SLC9A6 disrupts recycling endosomal function and elicits neurodegeneration and cell death.

Background: Christianson Syndrome, a recently identified X-linked neurodevelopmental disorder, is caused by mutations in the human gene SLC9A6 encoding the recycling endosomal alkali cation/proton exchanger NHE6. The patients have pronounced limitations in cognitive ability, motor skills and adaptive behaviour. However, the mechanistic basis for this disorder is poorly understood as few of the more than 20 mutations identified thus far have been studied in detail.

Comparing the efficacy of photodynamic and sonodynamic therapy in non-melanoma and melanoma skin cancer.

Sonodynamic therapy (SDT) involves the activation of a non-toxic sensitiser drug using low-intensity ultrasound to produce cytotoxic reactive oxygen species (ROS). Given the low tissue attenuation of ultrasound, SDT provides a significant benefit over the more established photodynamic therapy (PDT) as it enables activation of sensitisers at a greater depth within human tissue. In this manuscript, we compare the efficacy of aminolevulinic acid (ALA) mediated PDT and SDT in a squamous cell carcinoma (A431) cell line as well as the ability of these treatments to reduce the size of A431 ectopic tumours in mice.