Occurrence and characterization of rmtB-harbouring Salmonella and Escherichia coli isolates from a pig farm in the UK.

OBJECTIVES: To characterize and elucidate the spread of amikacin-resistant Enterobacteriaceae isolates from environmental samples on a pig farm in the UK, following the previous identification of index Salmonella isolates harbouring the rmtB gene, a 16S rRNA methylase. METHODS: Environmental samples were collected during two visits to a pig farm in the UK. Isolates were recovered using selective media (amikacin 128 mg/L) followed by real-time PCR and WGS to analyse rmtB-carrying Salmonella and Escherichia coli isolates. RESULTS: Salmonella and E. coli isolates harbouring the rmtB gene were detected at both farm visits. All Salmonella isolates were found to be monophasic S. enterica serovar Typhimurium variant Copenhagen of ST34. rmtB-harbouring E. coli isolates were found to be one of three STs: ST4089, ST1684 and ST34. Long-read sequencing identified the rmtB gene to be chromosomally located in Salmonella isolates and on IncFII-type plasmids in E. coli isolates. The results showed the rmtB gene to be flanked by IS26 elements and several resistance genes. CONCLUSIONS: We report on the occurrence of rmtB-harbouring Enterobacteriaceae on a pig farm in the UK. rmtB confers resistance to multiple aminoglycosides and this work highlights the need for surveillance to assess dissemination and risk.

An overview of outputs of Aboriginal- and Torres Strait Islander-related publications from University Departments of Rural Health in Australia; 2010-2021.

INTRODUCTION: Disparities in the health of Indigenous people and in the health of rural populations are well described. University Departments of Rural Health (UDRHs) in Australia are federally funded under a program to address ongoing challenges with health workforce distribution for rural and remote areas. They have a significant role in research in regional, rural and remote areas, including research related to Indigenous health. However, a comprehensive analysis of their contributions to original Indigenous health related to Indigenous health is lacking. OBJECTIVE: This study examines the contributions of UDRHs to Indigenous issues through analysis of publications of UDRHs focused on Indigenous health during the period 2010-2021. DESIGN: This paper examines a database of UDRH Indigenous-related publications from 2010 to 2021. FINDINGS: A total of 493 publications to which UDRHs contributed were analysed, including 354 original research articles. Health services research was the most common category, followed by epidemiology and papers exploring Indigenous culture and health. While health services research substantially increased over the period, the numbers of original research papers specifically focused on Indigenous workforce issues, whether related to Indigenous people, students or existing workforce was relatively small. DISCUSSION: This broad overview shows the nature and trends in Indigenous health research by UDRHs and makes evident a substantial contribution to Indigenous health research, reflecting their commitment to improving the health and well-being of Indigenous communities. CONCLUSIONS: The analysis can help direct future efforts, and future analyses should delve deeper into the impact of this research and further engage Indigenous researchers.

Equivocal diagnostics: Making a 'good' point-of-care test for elimination in global health.

What is a diagnostic test for? We might assume the answer to this question is straightforward. A good test would help identify what disease someone suffers from, assist health providers to determine the correct course of treatment and/or enable public health authorities to know and intervene in health at the level of the population. In this article, we show that what a specific diagnostic test is for, the value it holds for different actors, and what makes it good, or not, is often far from settled. We tell the story of the development and design of a rapid antibody test for onchocerciasis, or river blindness, tracking multiple iterations of the device through three configurational moments in the framing of onchocerciasis disease and reshaping of the global health innovation ecosystem. Efforts to build that ecosystem for diagnostics are often premised on the notion that public health needs for diagnostics are pre-given and stable; the challenge is seen to be how to incentivize investment and find a customer base for diagnostics in under-resourced settings. By contrast, we show that for any disease, diagnostic needs are both multiple and constantly in flux, and are unlikely to be met by a single, stand-alone product. In the case of the onchocerciasis Ov-16 rapid test, the failure to recognize and address the multiplicity and instability of diagnostic needs in the innovation process resulted in the development of a rapid point of care test that might be manufactured, procured and used, but is unloved by public health experts and commercial manufacturers alike. The equivocal value of the onchocerciasis rapid test, we suggest, reveals the inadequacy of the current global health innovation ecosystem for developing diagnostic 'goods'.

Milk recording data indicates the importance of fertility, including age at first calving, on the progression of first lactation cows to second lactation.

Dairy farmers do not recoup the rearing costs incurred from birth to first calving until second lactation but varying proportions of first lactation cows are removed from the herd before second calving. Herein, we used milk recording data to examine the outcomes and performance of first lactation cows to gain insight into farmer decisions to keep or remove them from the herd. An InterHerd+ dataset derived from 500 milk recording dairy herds in UK was used to examine first lactation cows which calved in 2020. Of 29,128 first lactation cows that calved in 2020, 82.6% remained within the herd and re-calved, 4.9% conceived but exited the herd before re-calving, 6.0% were served but exited the herd after failing to conceive and 6.6% exited the herd without being served. The fertility data on these cows support the logical conclusion that farmers retain cows that are served and conceive sooner, possibly in order to keep within a broadly seasonal calving pattern. Cows which were served but not conceived had a median AFC 16-20 days greater than the median AFC for those that conceived. Farmers may also be retaining cows with relatively high milk yields and lower somatic cell counts, or these parameters may be an indicator of a range of attributes affecting the farmer's decision. The data also suggest that farmers are rearing more replacements than required, because over one third of the cows removed in first lactation are never served, and 70% of these are sold within 120 days post-partum. These cows had a significantly older median age at first calving of 818 days, but their early removal without serving suggests there is an oversupply of replacements forcing farmers to dispose of these cows early in lactation. In order to develop a deeper understanding of herd turnover and replacement, future work could examine cow removals in lactation 2 onwards.

"A Huge Gap": Health Care Provider Perspectives on Cancer Screening for Aboriginal and Torres Strait Islander People in the Northern Territory.

Cancer is one of the leading causes of death for Aboriginal and Torres Strait Islander people in the Northern Territory (NT). Accessible and culturally appropriate cancer screening programs are a vital component in reducing the burden of cancer. Primary health care plays a pivotal role in facilitating the uptake of cancer screening in the NT, due to the significant challenges caused by large distances, limited resources, and cultural differences. This paper analyses health care provider perspectives and approaches to the provision of cancer screening to Aboriginal people in the NT that were collected as part of a larger study. Semi-structured interviews were conducted with 50 staff from 15 health services, including 8 regional, remote, and very remote primary health care (PHC) clinics, 3 hospitals, a cancer centre, and 3 cancer support services. Transcripts were thematically analysed. Cancer screening by remote and very remote PHC clinics in the NT is variable, with some staff seeing cancer screening as a "huge gap", while others see it as lower priority compared to other conditions due to a lack of resourcing and the overwhelming burden of acute and chronic disease. Conversely, some clinics see screening as an area where they are performing well, with systematic screening, targeted programs, and high screening rates. There was a large variation in perceptions of the breast screening and cervical screening programs. However, participants universally reported that the bowel screening kit was complicated and not culturally appropriate for their Aboriginal patients, which led to low uptake. System-level improvements are required, including increased funding and resourcing for screening programs, and for PHC clinics in the NT. Being appropriately resourced would assist PHC clinics to incorporate a greater emphasis on cancer screening into adult health checks and would support PHCs to work with local communities to co-design targeted cancer screening programs and culturally relevant education activities. Addressing these issues are vital for NT PHC clinics to address the existing cancer screening gaps and achieving the Australian Government pledge to be the first nation in the world to eliminate cervical cancer as a public health problem by 2035. The implementation of the National Lung Cancer Screening Program in 2025 also presents an opportunity to deliver greater benefits to Aboriginal communities and reduce the cancer burden.

Challenges for the management of Johne's disease in the UK: Expectation management, space, 'free riding', and vet-farmer communication.

Johne's disease in cattle is a significant global animal health challenge. Johne's disease is chronic, affecting the gastrointestinal tract of cattle and other ruminants and is caused by the bacteria Mycobacterium avium ssp. Paratuberculosis. Many countries have introduced schemes and programmes to try and control the spread of Johne's disease, including the UK. Despite efforts to control it, however, Johne's disease remains consistently ranked by UK producers as the top ranked disease negatively affecting productivity, indicating that schemes are not perceived to have solved the problem fully. Building on a global systematic review of the literature on barriers and solutions for Johne's disease control on-farm, we conducted an empirical study with over 400 farmers and 150 veterinary professionals across the UK. The study used workshops and semi-structured interviews to understand better the challenges dairy farmers and veterinarians face in implementing on-farm Johne's disease management schemes with the aim of identifying solutions. The study found that four main challenges are faced in the on-farm control of Johne's - (1) Management of farmer expectations around Johne's disease, with eradication near impossible, (2) Issues regarding space for segregation and the related economics of control (3) A 'free-riding' problem which can be influenced by the voluntary nature of control plans and (4) Challenges in vet-farmer communication, including levels of knowledge. Our findings have relevance for the control of Johne's disease in the UK and other countries, including for regions with voluntary and compulsory control programmes.

Implementation of One Health surveillance systems: Opportunities and challenges - lessons learned from the OH-EpiCap application.

As the complexity of health systems has increased over time, there is an urgent need for developing multi-sectoral and multi-disciplinary collaborations within the domain of One Health (OH). Despite the efforts to promote collaboration in health surveillance and overcome professional silos, implementing OH surveillance systems in practice remains challenging for multiple reasons. In this study, we describe the lessons learned from the evaluation of OH surveillance using OH-EpiCap (an online evaluation tool for One Health epidemiological surveillance capacities and capabilities), the challenges identified with the implementation of OH surveillance, and the main barriers that contribute to its sub-optimal functioning, as well as possible solutions to address them. We conducted eleven case studies targeting the multi-sectoral surveillance systems for antimicrobial resistance in Portugal and France, Salmonella in France, Germany, and the Netherlands, Listeria in The Netherlands, Finland and Norway, Campylobacter in Norway and Sweden, and psittacosis in Denmark. These evaluations facilitated the identification of common strengths and weaknesses, focusing on the organization and functioning of existing collaborations and their impacts on the surveillance system. Lack of operational and shared leadership, adherence to FAIR data principles, sharing of techniques, and harmonized indicators led to poor organization and sub-optimal functioning of OH surveillance systems. In the majority of studied systems, the effectiveness, operational costs, behavioral changes, and population health outcomes brought by the OH surveillance over traditional surveillance (i.e. compartmentalized into sectors) have not been evaluated. To this end, the establishment of a formal governance body with representatives from each sector could assist in overcoming long-standing barriers. Moreover, demonstrating the impacts of OH-ness of surveillance may facilitate the implementation of OH surveillance systems.

Mechanistic Insights Behind the Self-Assembly of Human Insulin under the Influence of Surface-Engineered Gold Nanoparticles.

Elucidating the underlying principles of amyloid protein self-assembly at nanobio interfaces is extremely challenging due to the diversity in physicochemical properties of nanomaterials and their physical interactions with biological systems. It is, therefore, important to develop nanoscale materials with dynamic features and heterogeneities. In this work, through engineering of hierarchical polyethylene glycol (PEG) structures on gold nanoparticle (GNP) surfaces, tailored nanomaterials with different surface properties and conformations (GNPs-PEG) are created for modulating the self-assembly of a widely studied protein, insulin, under amyloidogenic conditions. Important biophysical studies including thioflavin T (ThT) binding, circular dichroism (CD), surface plasmon resonance (SPR), and atomic force microscopy (AFM) showed that higher-molecular weight GNPs-PEG triggered the formation of amyloid fibrils by promoting adsorption of proteins at nanoparticle surfaces and favoring primary nucleation rate. Moreover, the modulation of fibrillation kinetics reduces the overall toxicity of insulin oligomers and fibrils. In addition, the interaction between the PEG polymer and amyloidogenic insulin examined using MD simulations revealed major changes in the secondary structural elements of the B chain of insulin. The experimental findings provide molecular-level descriptions of how the PEGylated nanoparticle surface modulates protein adsorption and drives the self-assembly of insulin. This facile approach provides a new avenue for systematically altering the binding affinities on nanoscale surfaces by tailoring their topologies for examining adsorption-induced fibrillogenesis phenomena of amyloid proteins. Together, this study suggests the role of nanobio interfaces during surface-induced heterogeneous nucleation as a primary target for designing therapeutic interventions for amyloid-related neurodegenerative disorders.

Communicating and disseminating One Health: successes of the One Health European Joint Programme.

The application of a One Health approach recognizes that human health, animal health, plant health and ecosystem health are intrinsically connected. Tackling complex challenges associated with foodborne zoonoses, antimicrobial resistance, and emerging threats is imperative. Therefore, the One Health European Joint Programme was established within the European Union research programme Horizon 2020. The One Health European Joint Programme activities were based on the development and harmonization of a One Health science-based framework in the European Union (EU) and involved public health, animal health and food safety institutes from almost all EU Member States, the UK and Norway, thus strengthening the cooperation between public, medical and veterinary organizations in Europe. Activities including 24 joint research projects, 6 joint integrative projects and 17 PhD projects, and a multicountry simulation exercise facilitated harmonization of laboratory methods and surveillance, and improved tools for risk assessment. The provision of sustainable solutions is integral to a One Health approach. To ensure the legacy of the work of the One Health European Joint Programme, focus was on strategic communication and dissemination of the outputs and engagement of stakeholders at the national, European and international levels.

Participant experiences of guided self-help Acceptance and Commitment Therapy for improving quality of life in muscle disease: a nested qualitative study within the ACTMus randomized controlled trial.

Introduction: In adults, muscle disease (MD) is typically a chronic long-term condition that can lead to a reduced quality of life (QoL). Previous research suggests that a psychological intervention, in particular Acceptance and Commitment Therapy (ACT), may help improve QoL for individuals living with chronic conditions such as MD. Methods: This nested qualitative study was incorporated within a randomized controlled trial which evaluated a guided self-help ACT intervention for people living with MD to explore their experiences of the intervention. Semi-structured interviews (n = 20) were conducted with those who had received ACT. Data were analyzed via thematic analysis. Results: There were four overarching themes. (1) Views on whether therapy sessions would help with a medical condition: participants' expectations regarding ACT varied. Some participants were skeptical about mindfulness. (2) I was able to look at things in a different way: participants described increased meaningful activity, greater awareness of thoughts and emotions and acceptance or adaptation to mobility problems. Some described improvement in the quality of relationships and a sense of feeling free. (3) Treating the body and the mind together: following the intervention participants noted that a holistic approach to healthcare is beneficial. (4) Intervention delivery: The remote delivery was generally seen as helpful for practical reasons and allowed participants to speak openly. Participants voiced a need for follow-up sessions. Discussion: Overall, the intervention was experienced as acceptable. Suggested improvements included de-emphasizing the role of mindfulness and adding follow-up sessions.

Nitric oxide and the resolution of inflammation: implications for atherosclerosis

The ubiquitous free radical, nitric oxide (NO), plays an important role in many biological processes including the regulation of the inflammatory response. Alterations in NO synthesis by endogenous systems likely influence inflammatory processes occurring in a wide range of diseases including many in the cardiovascular system (e.g. atherosclerosis). Progression of inflammatory conditions depends not only upon the recruitment and activation of inflammatory cells but also upon their subsequent removal from the inflammatory milieu. Apoptosis, or programmed cell death, is a fundamental process regulating inflammatory cell survival and is critically involved in ensuring the successful resolution of an inflammatory response. Apoptosis results in shutdown of secretory pathways and renders effete, but potentially highly histotoxic, cells instantly recognisable for non-inflammatory clearance by phagocytes (e.g., macrophages). However, dysregulation of apoptosis and phagocytic clearance mechanisms can have drastic consequences for development and resolution of inflammatory processes. In this review we highlight the complexities of NO-mediated regulation of inflammatory cell apoptosis and clearance by phagocytes and discuss the molecular mechanisms controlling these NO mediated effects. We believe that manipulation of pathways involving NO may have previously unrecognised therapeutic potential for limiting or resolving inflammatory and cardiovascular disease.