Journal Articles

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    General practitioner and nurse experiences of type 2 diabetes management and prescribing in primary care: a qualitative review following the introduction of funded SGLT2i/GLP1RA medications in Aotearoa New Zealand.
    (Cambridge University Press, 2024-09-16) Norman K; Mustafa ST; Cassim S; Mullins H; Clark P; Keenan R; Te Karu L; Murphy R; Paul R; Kenealy T; Chepulis L
    AIM: To explore the views of general practitioners (GPs) and nurses on type 2 diabetes (T2D) management, including the use of recently funded T2D medications in New Zealand (NZ) and their perceived barriers to providing optimal care. BACKGROUND: T2D is a significant health concern in NZ, particularly among Māori and Pacific adults. Characterised by prolonged hyperglycaemia, T2D is generally a progressive condition requiring long-term care. METHODS: Semi-structured interviews were conducted between July and December 2022 with 21 primary care clinicians (10 GPs and 11 nurses/nurse prescribers) from nine different general practice clinics across the Auckland and Waikato regions of NZ. Framework analysis was conducted to identify common themes in clinicians' perceptions and experiences with T2D management. FINDINGS: Three themes were identified: health-system factors, new medications, and solution-based approaches. Lack of clinician time, healthcare funding, staff shortages, and burn-out were identified as barriers to T2D management under health-system factors. The two newly funded medications, empagliflozin and dulaglutide, were deemed to be a positive change for T2D care in that they improved patient satisfaction and clinical outcomes, but several clinicians were hesitant to prescribe these medications. Participants suggested that additional education and specialist diabetes support would be helpful to inform optimal medication prescribing and that better use of a multi-disciplinary team (clinical and support staff) could support T2D care by reducing workload, addressing cultural gaps in healthcare delivery, and reducing burnout. An improved primary care work environment, including appropriate professional development to support prescribing of new medications and the value of collaboration with a non-regulated workforce, may be required to facilitate optimal T2D management in primary care. Future research should focus on interventions to increase support for both clinical teams and patients while adopting a culturally appropriate approach to increase patient satisfaction and improve health outcomes.
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    Zoonotic transmission of asymptomatic carriage Staphylococcus aureus on dairy farms in Canterbury, New Zealand.
    (Microbiology Society, 2024-12-04) Straub C; Taylor W; French NP; Murdoch DR; Priest P; Anderson T; Scott P
    Zoonotic pathogen transmission is of growing concern globally, with agricultural intensification facilitating interactions between humans, livestock and wild animals. Staphylococcus aureus is a major human pathogen, but it also causes mastitis in dairy cattle, leading to an economic burden on the dairy industry. Here, we investigated transmission within and between cattle and humans, including potential zoonotic transmission of S. aureus isolated from cattle and humans from three dairy farms and an associated primary school in New Zealand. Nasal swabs (N=170) were taken from healthy humans. Inguinal and combined nasal/inguinal swabs were taken from healthy cattle (N=1163). Whole-genome sequencing was performed for 96 S. aureus isolates (44 human and 52 cattle). Multilocus sequence typing and assessments of antimicrobial resistance and virulence were carried out. Potential within- and across-species transmission events were determined based on single nucleotide polymorphisms (SNPs). Thirteen potential transmission clusters were detected, with 12 clusters restricted to within-species and one potential zoonotic transmission cluster (ST5). Potential transmission among cattle was mostly limited to single age groups, likely because different age groups are managed separately on farms. While the prevalence of antimicrobial resistance (AMR) was low among both bovine and human isolates, the discovery of an extended-spectrum beta-lactamase gene (bla TEM-116) in a bovine isolate was concerning. This study provides evidence around frequency and patterns of potential transmission of S. aureus on dairy farms and highlights the AMR and virulence profile of asymptomatic carriage S. aureus isolates.
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    Impact of cell wall polysaccharide modifications on the performance of Pichia pastoris: novel mutants with enhanced fitness and functionality for bioproduction applications.
    (BioMed Central Ltd, 2024-02-17) Cheng B; Yu K; Weng X; Liu Z; Huang X; Jiang Y; Zhang S; Wu S; Wang X; Hu X
    BACKGROUND: Pichia pastoris is a widely utilized host for heterologous protein expression and biotransformation. Despite the numerous strategies developed to optimize the chassis host GS115, the potential impact of changes in cell wall polysaccharides on the fitness and performance of P. pastoris remains largely unexplored. This study aims to investigate how alterations in cell wall polysaccharides affect the fitness and function of P. pastoris, contributing to a better understanding of its overall capabilities. RESULTS: Two novel mutants of GS115 chassis, H001 and H002, were established by inactivating the PAS_chr1-3_0225 and PAS_chr1-3_0661 genes involved in β-glucan biosynthesis. In comparison to GS115, both modified hosts exhibited a looser cell surface and larger cell size, accompanied by faster growth rates and higher carbon-to-biomass conversion ratios. When utilizing glucose, glycerol, and methanol as exclusive carbon sources, the carbon-to-biomass conversion rates of H001 surpassed GS115 by 10.00%, 9.23%, and 33.33%, respectively. Similarly, H002 exhibited even higher increases of 32.50%, 12.31%, and 53.33% in carbon-to-biomass conversion compared to GS115 under the same carbon sources. Both chassis displayed elevated expression levels of green fluorescent protein (GFP) and human epidermal growth factor (hegf). Compared to GS115/pGAPZ A-gfp, H002/pGAPZ A-gfp showed a 57.64% higher GFP expression, while H002/pPICZα A-hegf produced 66.76% more hegf. Additionally, both mutant hosts exhibited enhanced biosynthesis efficiencies of S-adenosyl-L-methionine and ergothioneine. H001/pGAPZ A-sam2 synthesized 21.28% more SAM at 1.14 g/L compared to GS115/pGAPZ A-sam2, and H001/pGAPZ A-egt1E obtained 45.41% more ERG at 75.85 mg/L. The improved performance of H001 and H002 was likely attributed to increased supplies of NADPH and ATP. Specifically, H001 and H002 exhibited 5.00-fold and 1.55-fold higher ATP levels under glycerol, and 6.64- and 1.47-times higher ATP levels under methanol, respectively, compared to GS115. Comparative lipidomic analysis also indicated that the mutations generated richer unsaturated lipids on cell wall, leading to resilience to oxidative damage. CONCLUSIONS: Two novel P. pastoris chassis hosts with impaired β-1,3-D-glucan biosynthesis were developed, showcasing enhanced performances in terms of growth rate, protein expression, and catalytic capabilities. These hosts exhibit the potential to serve as attractive alternatives to P. pastoris GS115 for various bioproduction applications.
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    Amplifying Women's Voices in Menopause Research: The Importance of Inclusive Perspectives
    (John Wiley and Sons Ltd, 2025-02) Cronin C; Donevant S; Hughes K-A; Kaunonen M; Marcussen J; Wilson R
    Menopause, a significant life transition for half the global population, intersects biological, cultural and social dimensions. Despite its universal occurrence, menopause research has historically been dominated by biomedical perspectives, often neglecting women's voices and diverse experiences. This article highlights the importance of including women's perspectives in menopause research to ensure relevance, accuracy and equity. It explores cultural variations in menopause experiences, the impact of socioeconomic status and the often-overlooked emotional and psychological dimensions. This article advocates for participatory approaches, emphasising that women's involvement enhances research design, implementation and policy development. Evidence-based interventions that are tailored to the individual can better address the diverse needs of menopausal women. The discussion extends to addressing health disparities, calling for inclusive research and policies to ensure equitable access to care. Ultimately, empowering women through co-designed research and inclusive policies can transform the menopause journey into an enriching life phase, promoting resilience and inclusivity across communities. This paradigm shift in menopause research and policy highlights the need for diversity, collaboration and evidence-based approaches to improve health outcomes and quality of life for all women. PATIENT OR PUBLIC CONTRIBUTION: This article has been informed by a menopause service user group who discuss their experiences of menopause. The group was formed because of initial qualitative research and now meet on a regular basis to co-design and co-produce activities that inform ongoing research for the menopause taskforce.
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    N-Methyl-D-Aspartate Receptor Hypofunction in Meg-01 Cells Reveals a Role for Intracellular Calcium Homeostasis in Balancing Megakaryocytic-Erythroid Differentiation
    (Thieme Gruppe, 2020-04-14) Hearn JI; Green TN; Chopra M; Nursalim YNS; Ladvanszky L; Knowlton N; Blenkiron C; Poulsen RC; Singleton DC; Bohlander SK; Kalev-Zylinska ML
    The release of calcium ions (Ca2+) from the endoplasmic reticulum (ER) and related store-operated calcium entry (SOCE) regulate maturation of normal megakaryocytes. The N-methyl-D-aspartate (NMDA) receptor (NMDAR) provides an additional mechanism for Ca2+ influx in megakaryocytic cells, but its role remains unclear. We created a model of NMDAR hypofunction in Meg-01 cells using CRISPR-Cas9 mediated knockout of the GRIN1 gene, which encodes an obligate, GluN1 subunit of the NMDAR. We found that compared with unmodified Meg-01 cells, Meg-01-GRIN1 -/- cells underwent atypical differentiation biased toward erythropoiesis, associated with increased basal ER stress and cell death. Resting cytoplasmic Ca2+ levels were higher in Meg-01-GRIN1 -/- cells, but ER Ca2+ release and SOCE were lower after activation. Lysosome-related organelles accumulated including immature dense granules that may have contributed an alternative source of intracellular Ca2+. Microarray analysis revealed that Meg-01-GRIN1 -/- cells had deregulated expression of transcripts involved in Ca2+ metabolism, together with a shift in the pattern of hematopoietic transcription factors toward erythropoiesis. In keeping with the observed pro-cell death phenotype induced by GRIN1 deletion, memantine (NMDAR inhibitor) increased cytotoxic effects of cytarabine in unmodified Meg-01 cells. In conclusion, NMDARs comprise an integral component of the Ca2+ regulatory network in Meg-01 cells that help balance ER stress and megakaryocytic-erythroid differentiation. We also provide the first evidence that megakaryocytic NMDARs regulate biogenesis of lysosome-related organelles, including dense granules. Our results argue that intracellular Ca2+ homeostasis may be more important for normal megakaryocytic and erythroid differentiation than currently recognized; thus, modulation may offer therapeutic opportunities.
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    Antibiotic Use In Utero and Early Life and Risk of Chronic Childhood Conditions in New Zealand: Protocol for a Data Linkage Retrospective Cohort Study
    (JMIR Publications, 2025-02-28) Ram S; Corbin M; 't Mannetje A; Eng A; Kvalsig A; Baker M; Douwes J
    Background: The incidence of many common chronic childhood conditions has increased globally in the past few decades, which has been suggested to be potentially attributed to antibiotic overuse leading to dysbiosis in the gut microbiome. Objective: This linkage study will assess the role of antibiotic use in utero and in early life in the development of type 1 diabetes (T1D), attention-deficit/hyperactive disorder (ADHD), and inflammatory bowel disease. Methods: The study design involves several retrospective cohort studies using linked administrative health and social data from Statistics New Zealand’s Integrated Data Infrastructure. It uses data from all children who were born in New Zealand between October 2005 and December 2010 (N=334,204) and their mothers. Children’s antibiotic use is identified for 4 time periods (at pregnancy, at ≤1 year, at ≤2 years, and at ≤5 years), and the development of T1D, ADHD, and inflammatory bowel disease is measured from the end of the antibiotic use periods until death, emigration, or the end of the follow-up period (2021), whichever came first. Children who emigrated or died before the end of the antibiotic use period are excluded. Cox proportional hazards regression models are used while adjusting for a range of potential confounders. Results: As of September 2024, data linkage has been completed, involving the integration of antibiotic exposure and outcome variables for 315,789 children. Preliminary analyses show that both prenatal and early life antibiotic consumption is associated with T1D. Full analyses for all 3 outcomes will be completed by the end of 2025. Conclusions: This series of linked cohort studies using detailed, complete, and systematically collected antibiotic prescription data will provide critical new knowledge regarding the role of antibiotics in the development of common chronic childhood conditions. Thus, this study has the potential to contribute to the development of primary prevention strategies through, for example, targeted changes in antibiotic use.
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    Acceptance and commitment therapy for mild traumatic brain injury (ACTion-mTBI): a quasiexperimental feasibility study
    (BMJ Publishing Group Ltd, 2025-02-16) Faulkner J; Prouty D; Devlin L; Appleton D; Roche M; Below K; Moffat J; Snell D; Williams MN; Barker-Collo S; Theadom A
    OBJECTIVES: This study aimed to determine the feasibility of recruiting, implementing and delivering an acceptance and commitment therapy (ACT) intervention for mild traumatic brain injury (mTBI) (ACTion-mTBI) within a multidisciplinary outpatient mTBI rehabilitation services. The study also aimed to conduct a preliminary investigation of group differences between ACTion-mTBI and an equivalent cognitive behavioural therapy (CBT) intervention on various outcome measures and psychological treatment targets. DESIGN: A two-arm quasiexperimental feasibility study. SETTING: Five mTBI rehabilitation clinics throughout New Zealand. INTERVENTION: Psychologists working in mTBI rehabilitation clinics throughout New Zealand were trained to deliver ACTion-mTBI or CBT. Eligible participants were assigned to either of these interventions based on the psychologist available at the clinic they were referred to. ACTion-mTBI is a five sessions intervention that incorporates all six components of the ACT model. The CBT intervention is an equivalent intervention and incorporating all four components of the CBT model. Both interventions are adapted for an mTBI context. PRIMARY OUTCOME MEASURES: The primary outcomes were related to the feasibility of ACTion-mTBI. This included recruitment, retention and treatment adherence of participants, study procedure and fidelity of treatment delivery. SECONDARY OUTCOME MEASURES: To explore group differences between ACTion-mTBI and CBT on functional disability, postconcussion symptoms, mental health, valued living and psychological flexibility. RESULTS: The intervention proved feasible to implement with community-based mTBI rehabilitation services. Attrition rates were comparable between the two psychological interventions and fidelity to the treatments was high. At post-treatment, when covarying pretreatment scores, ACTion-mTBI had a significantly greater improvement in functional disability than CBT (moderate effect). ACTion-mTBI also had a significantly greater reduction in postconcussion symptoms, anxiety and stress. Promisingly, significant improvements in psychological flexibility was also found post-treatment. There were no group differences on depressive symptoms and valued living. CONCLUSION: We conclude that a full clinical trial of ACTion-mTBI for individuals with mTBI is feasible and warranted. TRIAL REGISTRATION NUMBER: ACTRN1262100059482.
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    Dropping the baton: Cognitive biases in emergency physicians.
    (PLOS, 2025-01-02) Ng M; Wong E; Sim GG; Heng PJ; Terry G; Yann FY
    Introduction Clinical medicine is becoming more complex and increasingly requires a team-based approach to deliver healthcare needs. This dispersion of cognitive reasoning across individuals, teams and systems (termed “distributed cognition”) means that our understanding of cognitive biases and errors must expand beyond traditional “in-the-head” individual mental models and focus on a broader “out-in-the-world” context instead. To our knowledge, no qualitative studies thus far have examined cognitive biases in clinical settings from a team-based sociocultural perspective. Our study therefore seeks to explore how cognitive biases and errors among emergency physicians (EPs) arise due to sociocultural influences and lapses in team cognition. Methodology Our study team comprised four EPs of different seniorities from three different institutions and local and international academics who provided qualitative methodological guidance. We adopted a constructivist paradigm and employed a reflexive thematic analysis approach which acknowledged our researcher reflexivity. We conducted seven focus group discussions with 25 EPs who were purposively sampled for maximum variation. Our research question was: How do sociocultural factors lead to cognitive biases and medical errors among EPs? Results Our themes coalesce around sociocultural pressures related to team psychology. In theme one, the EP is compelled by sociocultural pressures to blindly trust colleagues. In the second, the EP is obliged by cultural norms to be “nice” and neatly summarise cases into illness scripts during handovers. In the last, the EP is under immense pressure to follow conventional wisdom, comply with clinical protocols and not challenge inpatient specialists. Conclusion Cognitive biases and errors in clinical decision-making can arise due to lapses in distributed team cognition. Although this study focuses on emergency medicine, these pitfalls in team-based cognition are relevant across the entire continuum of care and across all specialties of medicine. The hyperacute nature of emergency medicine merely exacerbates and condenses these into a compressed timeframe. Indeed, similar relays are run every day in every discipline of medicine, with the same unified goal of doing the best for our patients while not committing cognitive errors and dropping the baton.
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    Healthcare performance of leprosy management in peripheral health facilities of Dhanusa and Mahottari, Nepal.
    (BioMed Central Ltd, 2025-12) Mahato RK; Ghimire U; Bajracharya B; K C B; Bam D; Ghimire D; Pyakurel UR; Hayman DTS; Pandey BD; Das CL; Paudel KP
    BACKGROUND: The global elimination of leprosy transmission by 2030 is a World Health Organization (WHO) target. Nepal's leprosy elimination program depends on early case diagnosis and the performance of health workers and facilities. The knowledge and skills of paramedical staff (Leprosy Focal Person, LFP) and case documentation and management by health facilities are therefore key to the performance of health care services. METHODS: The performance of health workers and facilities was evaluated through a combined cross-sectional and retrospective study approach of 31 health facilities and their LFPs in Dhanusa and Mahottari Districts in Madhesh Province, Nepal. An average of 6 patients (paucibacillary, PB, or multibacillary, MB) per health facility registered within the 2018/2019 fiscal year were also enrolled in the study. LFP knowledge (e.g., of the three cardinal signs) and skills (e.g., nerve palpation) and facility processes (e.g., record keeping) were scored (e.g., 0, 1) and then rescaled to a proportion, where 1 is perfect. Internal benchmarking was used to guide performance management. RESULTS: Overall LFP knowledge and skill scores of health workers ranged from 0.16 to 0.63 (median 0.53, 95% confidence interval (CI), 0.46-0.6). Case documentation scores ranged from 0.15 to 0.87 (median 0.37, 95% CI 0.36-0.38), case management scores from 0.38 to 0.79 (median 0.54, 95% CI 0.53-0.55) and overall healthcare scores from 0.36-0.62 (median 0.48, 95% CI 0.47-0.49). Leprosy-related training was significantly related to the knowledge and skills of the health workers. All identified cases (n = 187) adhered to the complete treatment and release after treatment (RFT) scheme, out of which 84.5% were satisfied with the service they were provided. Leprosy disability and ear hand and feet (EHF) scores were not significantly reduced in treated patients during the study period, but counseling by LFPs significantly improved cases' positive beliefs and practices regarding self-care. CONCLUSION: Overall leprosy care median performance was low (53%) and can be improved by evidenced-based training, onsite coaching, monitoring, and supervision to facilitate leprosy transmission elimination. The results highlight many of the challenges facing leprosy elimination programs.
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    Efficient Limb Range of Motion Analysis from a Monocular Camera for Edge Devices.
    (MDPI (Basel, Switzerland), 2025-01-22) Yan X; Zhang L; Liu B; Qu G; Amerini I; Russo P; Di Ciaccio F
    Traditional limb kinematic analysis relies on manual goniometer measurements. With computer vision advancements, integrating RGB cameras can minimize manual labor. Although deep learning-based cameras aim to offer the same ease as manual goniometers, previous approaches have prioritized accuracy over efficiency and cost on PC-based devices. Nevertheless, healthcare providers require a high-performance, low-cost, camera-based tool for assessing upper and lower limb range of motion (ROM). To address this, we propose a lightweight, fast, deep learning model to estimate a human pose and utilize predicted joints for limb ROM measurement. Furthermore, the proposed model is optimized for deployment on resource-constrained edge devices, balancing accuracy and the benefits of edge computing like cost-effectiveness and localized data processing. Our model uses a compact neural network architecture with 8-bit quantized parameters for enhanced memory efficiency and reduced latency. Evaluated on various upper and lower limb tasks, it runs 4.1 times faster and is 15.5 times smaller than a state-of-the-art model, achieving satisfactory ROM measurement accuracy and agreement with a goniometer. We also conduct an experiment on a Raspberry Pi, illustrating that the method can maintain accuracy while reducing equipment and energy costs. This result indicates the potential for deployment on other edge devices and provides the flexibility to adapt to various hardware environments, depending on diverse needs and resources.