133 research outputs found

    Cognitive-enhancing effects of angiotensin IV

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    Angiotensin IV is a derivative of the potent vasoconstrictor angiotensin II and it has been shown to enhance acquisition, consolidation and recall in animal models of learning and memory when administered centrally or peripherally. Whether changes in angiotensin IV activity underlie the cognitive effects of those cardiovascular drugs designed to disrupt the peripheral renin-angiotensin system in humans remains undetermined, but angiotensin IV appears to be a worthy candidate for consideration in drug development programmes. The mechanism of action of angiotensin IV is still debated, although its AT4 receptor has been convincingly identified as being insulin-regulated amino peptidase, which is also known as oxytocinase and placental leucine aminopeptidase. It is speculated that angiotensin IV may interact with insulin-regulated amino peptidase to enhance neuronal glucose uptake, prevent metabolism of other neuroactive peptides, induce changes in extracellular matrix molecules, or induce release of acetylcholine and/or dopamine. All of these things may be responsible for the beneficial effects on cognition, but none of them are yet proven. Importantly, strain differences in murine responses to angiotensin IV suggest that some individuals may benefit from drugs targeted to the AT4 receptor whilst others may be refractory. At present it thus appears that those individuals with the poorest baseline cognition may receive greatest benefit, but possible genetic differences in responses to angiotensin IV cannot be ruled-out

    Sexually dimorphic effects of prenatal alcohol exposure on the murine skeleton

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    Background: Prenatal alcohol exposure (PAE) can result in lifelong disabilities known as foetal alcohol spectrum disorder (FASD) and is associated with childhood growth deficiencies and increased bone fracture risk. However, the effects of PAE on the adult skeleton remain unclear and any potential sexual dimorphism is undetermined. Therefore, we utilised a murine model to examine sex differences with PAE on in vitro bone formation, and in the juvenile and adult skeleton. Methods: Pregnant C57BL/6J female mice received 5% ethanol in their drinking water during gestation. Primary calvarial osteoblasts were isolated from neonatal offspring and mineralised bone nodule formation and gene expression assessed. Skeletal phenotyping of 4- and 12-week-old male and female offspring was conducted by micro-computed tomography (µCT), 3-point bending, growth plate analyses, and histology.Results: Osteoblasts from male and female PAE mice displayed reduced bone formation, compared to control (≤30%). Vegfa, Vegfb, Bmp6, Tgfbr1, Flt1 and Ahsg were downregulated in PAE male osteoblasts only, whilst Ahsg was upregulated in PAE females. In 12-week-old mice, µCT analysis revealed a sex and exposure interaction across several trabecular bone parameters. PAE was detrimental to the trabecular compartment in male mice compared to control, yet PAE females were unaffected. Both male and female mice had significant reductions in cortical parameters with PAE. Whilst male mice were negatively affected along the tibial length, females were only distally affected. Posterior cortical porosity was increased in PAE females only. Mechanical testing revealed PAE males had significantly reduced bone stiffness compared to controls; maximum load and yield were reduced in both sexes. PAE had no effect on total body weight or tibial bone length in either sex. However, total growth plate width in male PAE mice compared to control was reduced, whilst female PAE mice were unaffected. 4-week-old mice did not display the altered skeletal phenotype with PAE observed in 12-week-old animals. Conclusions: Evidence herein suggests, for the first time, that PAE exerts divergent sex effects on the skeleton, possibly influenced by underlying sex-specific transcriptional mechanisms of osteoblasts. Establishing these sex differences will support future policies and clinical management of FASD.<br/

    Molecular Phylogeny of Edge Hill Virus Supports its Position in the Yellow Fever Virus Group and Identifies a New Genetic Variant

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    Edge Hill virus (EHV) is a mosquito-borne flavivirus isolated throughout Australia during mosquito surveillance programs. While not posing an immediate threat to the human population, EHV is a taxonomically interesting flavivirus since it remains the only member of the yellow fever virus (YFV) sub-group to be detected within Australia. Here we present both an antigenic and genetic investigation of collected isolates, and confirm taxonomic classification of the virus within the YFV-group. Isolates were not clustered based on geographical origin or time of isolation, suggesting that minimal genetic evolution of EHV has occurred over geographic distance or time within the EHV cluster. However, two isolates showed significant differences in antigenic reactivity patterns, and had a much larger divergence from the EHV prototype (19% nucleotide and 6% amino acid divergence), indicating a distinct subtype or variant within the EHV subgroup

    Family physicians\u27 responses to personal protective equipment shortages in four regions in Canada: a qualitative study.

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    BACKGROUND: Despite well-documented increased demands and shortages of personal protective equipment (PPE) during previous disease outbreaks, health systems in Canada were poorly prepared to meet the need for PPE during the COVID-19 pandemic. In the primary care sector, PPE shortages impacted the delivery of health services and contributed to increased workload, fear, and anxiety among primary care providers. This study examines family physicians\u27 (FPs) response to PPE shortages during the first year of the COVID-19 pandemic to inform future pandemic planning. METHODS: As part of a multiple case study, we conducted semi-structured qualitative interviews with FPs across four regions in Canada. During the interviews, FPs were asked to describe the pandemic-related roles they performed over different stages of the pandemic, facilitators and barriers they experienced in performing these roles, and potential roles they could have filled. Interviews were transcribed and a thematic analysis approach was employed to identify recurring themes. For the current study, we examined themes related to PPE. RESULTS: A total of 68 FPs were interviewed across the four regions. Four overarching themes were identified: 1) factors associated with good PPE access, 2) managing PPE shortages, 3) impact of PPE shortages on practice and providers, and 4) symbolism of PPE in primary care. There was a wide discrepancy in access to PPE both within and across regions, and integration with hospital or regional health authorities often resulted in better access than community-based practices. When PPE was limited, FPs described rationing and reusing these resources in an effort to conserve, which often resulted in anxiety and personal safety concerns. Many FPs expressed that PPE shortages had come to symbolize neglect and a lack of concern for the primary care sector in the pandemic response. CONCLUSIONS: During the COVID-19 pandemic response, hospital-centric plans and a lack of prioritization for primary care led to shortages of PPE for family physicians. This study highlights the need to consider primary care in PPE conservation and allocation strategies and to examine the influence of the underlying organization of primary care on PPE distribution during the pandemic

    Development of a primary care pandemic plan informed by in-depth policy analysis and interviews with family physicians across Canada during COVID-19: A qualitative case study protocol

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    Introduction Given the recurrent risk of respiratory illness-based pandemics, and the important roles family physicians play during public health emergencies, the development of pandemic plans for primary care is imperative. Existing pandemic plans in Canada, however, do not adequately incorporate family physicians\u27 roles and perspectives. This policy and planning oversight has become increasingly evident with the emergence of the novel coronavirus disease, COVID-19, pandemic. This study is designed to inform the development of pandemic plans for primary care through evidence from four provinces in Canada: British Columbia, Newfoundland and Labrador, Nova Scotia, and Ontario. Methods and analysis We will employ a multiple-case study of regions in four provinces. Each case consists of a mixed methods design which comprises: (1) a chronology of family physician roles in the COVID-19 pandemic response; (2) a provincial policy analysis; and (3) qualitative interviews with family physicians. Relevant policy and guidance documents will be identified through targeted, snowball and general search strategies. Additionally, these policy documents will be analysed to identify gaps and/or emphases in existing policies and policy responses. Interviews will explore family physicians\u27 proposed, actual and potential roles during the pandemic, the facilitators and barriers they have encountered throughout and the influence of gender on their professional roles. Data will be thematically analysed using a content analysis framework, first at the regional level and then through cross-case analyses. Ethics and dissemination Approval for this study has been granted by the Research Ethics of British Columbia, the Health Research Ethics Board of Newfoundland and Labrador, the Nova Scotia Health Authority Research Ethics Board and the Western University Research Ethics Board. Findings will be disseminated via conferences and peer-reviewed publications. Evidence and lessons learnt will be used to develop tools for government ministries, public health units and family physicians for improved pandemic response plans for primary care

    Family physician leadership during the COVID-19 pandemic: roles, functions and key supports.

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    PURPOSE: Strong leadership in primary care is necessary to coordinate an effective pandemic response; however, descriptions of leadership roles for family physicians are absent from previous pandemic plans. This study aims to describe the leadership roles and functions family physicians played during the COVID-19 pandemic in Canada and identify supports and barriers to formalizing these roles in future pandemic plans. DESIGN/METHODOLOGY/APPROACH: This study conducted semi-structured qualitative interviews with family physicians across four regions in Canada as part of a multiple case study. During the interviews, participants were asked about their roles during each pandemic stage and the facilitators and barriers they experienced. Interviews were transcribed and a thematic analysis approach was used to identify recurring themes. FINDINGS: Sixty-eight family physicians completed interviews. Three key functions of family physician leadership during the pandemic were identified: conveying knowledge, developing and adapting protocols for primary care practices and advocacy. Each function involved curating and synthesizing information, tailoring communications based on individual needs and building upon established relationships. PRACTICAL IMPLICATIONS: Findings demonstrate the need for future pandemic plans to incorporate formal family physician leadership appointments, as well as supports such as training, communication aides and compensation to allow family physicians to enact these key roles. ORIGINALITY/VALUE: The COVID-19 pandemic presents a unique opportunity to examine the leadership roles of family physicians, which have been largely overlooked in past pandemic plans. This study\u27s findings highlight the importance of these roles toward delivering an effective and coordinated pandemic response with uninterrupted and safe access to primary care

    Absolute Energy Measurements with Superconducting Transition-Edge Sensors for Muonic X-ray Spectroscopy at 44 keV

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    Superconducting transition-edge sensor (TES) microcalorimeters have great utility in x-ray applications owing to their high energy resolution, good collecting efficiency and the feasibility of being multiplexed into large arrays. In this work, we develop hard x-ray TESs to measure the absolute energies of muonic-argon (μ\mu-Ar) transition lines around 44 keV and 20 keV. TESs with sidecar absorbers of different heat capacities were fabricated and characterized for their energy resolution and calibration uncertainty. We achieved ~ 1 eV absolute energy measurement accuracy at 44 keV, and < 12 eV energy resolution at 17.5 keV
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