Publications by authors named "Paul Worley"

Background: General practice is pivotal in delivering mental health care within communities, yet the attitudes and professional factors influencing this provision remain underexplored. This study seeks to understand the perspective of general practice staff around the professional factors that influence the provision of primary mental health care.

Methods: A qualitative study was conducted with semi-structured interviews of 14 general practice staff involved in mental health care.

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Establishing new medical schools in medically under-served regions is suggested as part of the solution to the problem of doctor shortages and maldistributions. Establishing a new medical school is, however, a complex undertaking with high financial and political stakes. Critically, the evidence-base for this significant activity has not previously been elucidated.

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Article Synopsis
  • - The study highlights the significant issue of type 2 diabetes in Aboriginal communities, particularly focusing on Ngarrindjeri Country in South Australia, and criticizes the prevalent Western biomedical frameworks that overlook local contexts and strengths.
  • - Utilizing a combination of Aboriginal and Western research methods, the study collected qualitative data from 15 participants through yarning sessions, identifying barriers rooted in the impacts of colonization, as well as community strengths that support diabetes care.
  • - The findings suggest that despite facing numerous challenges, Aboriginal people in the area possess unique resources and capabilities to combat diabetes, emphasizing the need for health initiatives that respect local knowledge and prioritize community-led, holistic approaches over traditional medical models.
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Multiple neurodegenerative diseases are characterized by aberrant proteinaceous accumulations of tau. Here, we report a RING-in-between-RING-type E3 ligase, TRIAD3A, that functions as an autophagy adaptor for tau. TRIAD3A(RNF216) is an essential gene with mutations causing age-progressive neurodegeneration.

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Background: Limited access to specialist medical services is a major barrier to healthcare in rural areas. We compared rural-urban specialist doctor consultations outside hospital by older adults (≥ 60 years) across South Australia.

Methods: Cross-sectional data were available from the South Australia's Department of Health.

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Background: Establishing a new medical school is a significant venture involving many complex political, social, economic, educational, and organisational considerations. The published literature on the process of establishing a new medical school is, however, under-developed with minimal empirical research and no explicit reference to theory. This research sought to address these gaps and establish an empirical and theoretical evidence-base for the process of new medical school establishment in diverse contexts, particularly medically under-served areas.

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Background: The demand for mental health services in Australia is substantial and has grown beyond the capacity of the current workforce. As a result, it is currently difficult for many to access secondary healthcare providers. Within the secondary healthcare sector, however, peer workers who have lived experience of managing mental health conditions have been increasingly employed to intentionally use their journey of recovery in supporting others living with mental health conditions and their communities.

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Aim Of The Study: Neuronal pentraxin-2 (NPTX2) is a synaptic protein responsible for modulating plasticity at excitatory synapses. While the role of NPTX2 as a novel synaptic biomarker in cognitive disorders has been elucidated recently, its role in idiopathic normal pressure hydrocephalus (iNPH) is not yet understood.

Clinical Rationale For Study: To determine if NPTX2 predicts cognition in patients with iNPH, and whether it could serve as a predictive marker for shunt outcomes.

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Background: Analgesic tolerance due to long-term use of morphine remains a challenge for pain management. Morphine acts on μ-opioid receptors and downstream of the phosphatidylinositol 3-kinase signaling pathway to activate the mammalian target of rapamycin (mTOR) pathway. Rheb is an important regulator of growth and cell-cycle progression in the central nervous system owing to its critical role in the activation of mTOR.

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Sleep and circadian rhythm disruption (SCRD) is commonly observed in aging, especially in individuals who experience progressive cognitive decline to mild cognitive impairment (MCI) and Alzheimer's disease (AD). However, precise molecular mechanisms underlying the association between SCRD and aging are not fully understood. Orexin A is a well-characterized "sleep neuropeptide" that is expressed in hypothalamic neurons and evokes wake behavior.

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How neuronal signaling affects brain myelination remains poorly understood. We show dysregulated neuronal RHEB-mTORC1-DLK1 axis impairs brain myelination. Neuronal Rheb cKO impairs oligodendrocyte differentiation/myelination, with activated neuronal expression of the imprinted gene Dlk1.

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Objective: This study examined whether cerebrospinal fluid (CSF) baseline levels of the synaptic protein NPTX2 predict time to onset of symptoms of mild cognitive impairment (MCI), both alone and when accounting for traditional CSF Alzheimer's disease (AD) biomarker levels. Longitudinal NPTX2 levels were also examined.

Methods: CSF was collected longitudinally from 269 cognitively normal BIOCARD Study participants (mean baseline age = 57.

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The calcium-selective ion channel Orai1 has a complex role in bone homeostasis, with defects in both bone production and resorption detected in Orai1 germline knock-out mice. To determine whether Orai1 has a direct, cell-intrinsic role in osteoblast differentiation and function, we bred Orai1 flox/flox (Orai1fl/fl) mice with Runx2-cre mice to eliminate its expression in osteoprogenitor cells. Interestingly, Orai1 was expressed in a mosaic pattern in Orai1fl/fl-Runx2-cre bone.

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Complement overactivation mediates microglial synapse elimination in neurological diseases such as Alzheimer's disease (AD) and frontotemporal dementia (FTD), but how complement activity is regulated in the brain remains largely unknown. We identified that the secreted neuronal pentraxin Nptx2 binds complement C1q and thereby regulates its activity in the brain. Nptx2-deficient mice show increased complement activity, C1q-dependent microglial synapse engulfment, and loss of excitatory synapses.

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Cocaine-induced changes in the expression of the glutamate-related scaffolding protein Homer2 influence this drug's psychostimulant and rewarding properties. In response to neuronal activity, Homer2 is phosphorylated on S117/S216 by calcium-calmodulin kinase IIα (CaMKIIα), which induces a rapid dissociation of mGlu5-Homer2 scaffolds. Herein, we examined the requirement for Homer2 phosphorylation in cocaine-induced changes in mGlu5-Homer2 coupling, to include behavioral sensitivity to cocaine.

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Introduction: It is now 25 years since the Riverland health service began its partnership with Flinders University to create the Parallel Rural Community Curriculum (PRCC) in rural South Australia. What started as a workforce program quickly became a successful disruptive technology for broader pedagogy in medical education. Despite more graduates of the PRCC choosing rural practice compared with their urban rotation-based colleagues, local medical workforce crises have persisted.

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Background: Memory deficits are central to many neuropsychiatric diseases. During acquisition of new information, memories can become vulnerable to interference, yet mechanisms that underlie interference are unknown.

Methods: We describe a novel transduction pathway that links the NMDA receptor (NMDAR) to AKT signaling via the immediate early gene Arc and evaluate its role in memory.

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Article Synopsis
  • - Developed a new technique called soma-targeted Cal-Light (ST-Cal-Light) that tags only active neurons by converting calcium rises from action potentials into gene expression, improving the accuracy and reducing light needed for neuronal labeling.
  • - ST-Cal-Light enhances the identification of engaged neurons across various behaviors, such as fear conditioning and social interactions, and shows promise in alleviating seizure symptoms by targeting specific neurons in the hippocampus.
  • - The creation of a ST-Cal-Light knock-in mouse allows researchers to selectively tag active neurons based on their location or cell type, facilitating in-depth studies of neural circuits and their connections to behavior at a high level of detail.
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Background: Hepatocellular carcinoma (HCC) early diagnosis remains a challenge to date. Alpha-feto protein, though less sensitive remains widely used for both diagnosis and prognosis. Recently however, a number of molecular biomarkers have been suggested as alternatives to Alpha feto protein, especially for early diagnosis.

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Calcium signalling in platelets through store operated Ca entry (SOCE) or receptor-operated Ca entry (ROCE) mechanisms is crucial for platelet activation and function. Orai1 proteins have been implicated in platelet's SOCE. In this study we evaluated the contribution of Orai1 proteins to these processes using washed platelets from adult mice from both genders with platelet-specific deletion of the gene (Orai1; Pf4-Cre termed as Orai1) since mice with ubiquitous Orai1 deficiency show early lethality.

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Objective: Perinatal emotional well-being is more than the presence or absence of depressive and anxiety disorders; it encompasses a wide range of factors that contribute to emotional well-being. This study compares perinatal well-being between women living in metropolitan and rural regions.

Design: Prospective, longitudinal cohort.

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The mechanistic target of rapamycin (mTOR) signals through the mTOR complex 1 (mTORC1) and the mTOR complex 2 to maintain cellular and organismal homeostasis. Failure to finely tune mTOR activity results in metabolic dysregulation and disease. While there is substantial understanding of the molecular events leading mTORC1 activation at the lysosome, remarkably little is known about what terminates mTORC1 signaling.

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Aim: We aim to promote discussion about an Indigenous Cultural Identity of Research Authors Standard (ICIRAS) for academic journal publications.

Context: This is based on a gap in research publishing practice where Indigenous peoples' identity is not systematically and rigorously flagged in rural health research publications. There are widespread reforms, in different research areas, to counter the reputation of scientific research as a vehicle of racism and discrimination against the world's Indigenous peoples.

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The Indigenous Cultural Identity of Research Authors Standard (ICIRAS) is based on a gap in research publishing practice where Indigenous peoples' identity is not systematically and rigorously recognised in rural health research publications. There are widespread reforms, in different research areas, to counter the reputation of scientific research as a vehicle of racism and discrimination. Reflecting on these broader movements, the editorial teams of three rural health journals - Rural and Remote Health, the Australian Journal of Rural Health, and the Canadian Journal of Rural Medicine - adopted a policy of 'Nothing about Indigenous Peoples, without Indigenous Peoples'.

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Article Synopsis
  • T cell acute lymphoblastic leukemia (T-ALL) is a severe type of cancer involving immature T cells, and current treatments often fail, leading to relapses and poor outcomes.
  • Researchers identified RHEB, a key regulator of the mTOR signaling pathway, as a promising target for therapy in T-ALL.
  • The study showed that disabling RHEB in T-ALL cells caused cell death by disrupting nucleotide production, and this approach also reduced tumor growth in animal models, suggesting a potential effective treatment strategy.
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