624 research outputs found

    What’s Love Got to Do with It?

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    The life and work of student life professionals provide the glue in the academy. Being attentive to students’ health, well-being, success, and leadership development is what we do. It is what keeps the heart of our institutions beating. While dedication to this field requires passion, it can also run us dry. Love for the profession and love for oneself are essential to be whole, resilient professionals and human beings. Professional development includes personal development. This article is both a scholarly personal narrative and a call to action. It weaves the voices of a young professional and her mentor through their own journeys of discovery with research in the importance of heart in higher education. This article offers insight about the need to integrate the essential inner work of self-love into our profession

    Exploring the role of metals and senescence in cutaneous wound repair

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    Acute wound healing involves a tightly regulated cascade of cellular signalling and functional events. Deterioration at any stage of this sophisticated system can lead to healing impairment and chronic, non-healing wounds. Chronic wounds, which are prevalent in the elderly and diabetic, are a global socioeconomic burden and remain a major area of clinical unmet need. Improved understanding of the cellular and molecular aetiology of chronic wounds is essential to develop new therapies. The aim of this work was to explore the role of cellular senescence and the metallome in governing normal and pathological wound repair. Novel data presented in this thesis show increased senescence in both aged and diabetic wounds, while biologically-important metals, such as calcium, were reduced. Transcriptional profiling of wounds strongly linked the transcriptome, metallome and senescence. A direct role for senescence in pathological healing was mechanistically demonstrated in vitro, ex vivo and in vivo. Crucially, pharmacological inhibition of the explicated senescence receptor, Cxcr2, accelerated diabetic wound healing in vivo. Collectively, these data reveal a hitherto unappreciated role for Cxcr2 in mediating cellular senescence during pathological skin repair. Global profiling of the wound metallome highlighted significant changes in wound iron levels during late-stage healing. In vitro studies uncovered a new role for iron in mediating extracellular matrix deposition during wound remodelling, while reduced iron levels in diabetic wounds correlated with impaired ECM deposition. In summary, temporospatial metallome profiling identified multiple defects in metal-linked cellular processes in the pathological wound environment. Taken together, the research platform delivered in this work will provide an unprecedented opportunity to further interrogate transcriptional and functional relationships between cellular senescence and the metallome in wound repair. Indeed, this research may underpin the development of novel, efficacious metal-targeted therapies for chronic healing wounds in the future

    The role of estrogen in cutaneous ageing and repair

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    © 2017 Elsevier B.V. Combined advances in modern medical practice and increased human longevity are driving an ever-expanding elderly population. Females are particularly at risk of age-associated pathology, spending more of their lives in a post-menopausal state. Menopause, denoted by a rapid decline in serum sex steroid levels, accelerates biological ageing across the body's tissues. Post-menopause physiological changes are particularly noticeable in the skin, which loses structural architecture and becomes prone to damage. The sex steroid most widely discussed as an intrinsic contributor to skin ageing and pathological healing is 17β-estradiol (or estrogen), although many others are involved. Estrogen deficiency is detrimental to many wound-healing processes, notably inflammation and re-granulation, while exogenous estrogen treatment widely reverses these effects. Over recent decades, many of the molecular and cellular correlates to estrogen's beneficial effect on normal skin homeostasis and wound healing have been reported. However, disparities still exist, particularly in the context of mechanistic studies investigating estrogen receptor signalling and its potential cellular effects. New molecular techniques, coupled with increased understanding of estrogen in skin biology, will provide further opportunities to develop estrogen receptor-targeted therapeutics

    Senescence in Wound Repair: Emerging Strategies to Target Chronic Healing Wounds

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    © Copyright © 2020 Wilkinson and Hardman. Cellular senescence is a fundamental stress response that restrains tumour formation. Yet, senescence cells are also present in non-cancerous states, accumulating exponentially with chronological age and contributing to age- and diabetes-related cellular dysfunction. The identification of hypersecretory and phagocytic behaviours in cells that were once believed to be non-functional has led to a recent explosion of senescence research. Here we discuss the profound, and often opposing, roles identified for short-lived vs. chronic tissue senescence. Transiently induced senescence is required for development, regeneration and acute wound repair, while chronic senescence is widely implicated in tissue pathology. We recently demonstrated that sustained senescence contributes to impaired diabetic healing via the CXCR2 receptor, which when blocked promotes repair. Further studies have highlighted the beneficial effects of targeting a range of senescence-linked processes to fight disease. Collectively, these findings hold promise for developing clinically viable strategies to tackle senescence in chronic wounds and other cutaneous pathologies

    A Nurse\u27s Journey with Cultural Humility: Acknowledging Personal and Professional Unintentional Indigenous-specific Racism

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    This is a first-person reflection of my journey through cultural humility to identify a connection between my inherent beliefs about Indigenous Peoples and Indigenous-specific systemic racism. The co-authors of this paper provided guidance, mentorship, and support in organizing the framework due to the challenging and sensitive nature of the content. As part of my relational practice, I worked with a Cree scholar to write this paper. As a descendant of white European colonial settlers, I grew up in a small community in western Canada populated by people of similar backgrounds. My exposure to Indigenous Peoples and culture was very minimal; however, conversations and attitudes about Indigenous Peoples generally centered around negative and racist stereotypes. Childhood games and jokes insidiously contributed to the construction of my worldview by dehumanizing, belittling, and humiliating Indigenous Peoples. A necessary part of my journey was to recognize how these words and attitudes have informed my worldview and at the same time hurt Indigenous Peoples. Historical facts of Indigenous treatment were brushed off or minimized as something that happened in the past. Although sharing my experience is uncomfortable, I am compelled to identify and acknowledge how the deep-rooted beliefs and attitudes that I have towards Indigenous Peoples have been shaped by my education, culture, and experiences. I hope that my own developing journey with cultural humility may serve as a guide to deconstructing the historical, personal, and professional ways in which Indigenous-specific racism exists and is perpetuated in health care. My own first steps are an open invitation for the nursing profession to similarly begin to address unintentional and intentional racism in healthcare. By understanding Canadian history, committing to allyship, advocating for social justice, actively intervening by speaking up, and integrating trauma-informed care/principles into our practice, we may begin to effectively address Indigenous-specific racism in health care. Résumé Il s’agit d’une réflexion personnelle sur mon parcours en matière d’humilité culturelle afin d’identifier le lien entre mes croyances inhérentes au sujet des peuples autochtones et du racisme systémique dont ils sont victimes. Les coauteures de cet article ont fourni des conseils, de l’encadrement et du soutien pour développer le contexte en raison de la nature délicate du contenu. Dans le cadre de ma pratique relationnelle, j’ai rédigé cet article en collaboration avec un universitaire crie. Je suis descendante de colons européens blancs, j’ai grandi dans une petite communauté de l’ouest du Canada entourée de personnes aux origines similaires. J’ai été très peu exposée aux Autochtones et à leur culture, toutefois, les conversations et les mentalités les concernant étaient habituellement négatives et racistes. Les jeux et les blagues de mon enfance ont influencé ma conception du monde en déshumanisant, rabaissant et humiliant les peuples autochtones. Une des étapes cruciales de mon cheminement a été de reconnaître la façon dont ces mots et ces mentalités ont influencé ma perception du monde et par la même occasion, ont blessé les Autochtones. Les faits historiques et les traitements qui leur étaient réservés ont été balayés du revers de la main ou atténués en raison de leur nature ancienne. Bien que je sois mal à l’aise de vous raconter mon expérience, je me vois obligée d’identifier et de reconnaître que mes croyances et mes mentalités profondément enracinées envers les Autochtones ont été façonnées par mon éducation, ma culture et mes expériences. Je souhaite que mon cheminement vers l’humilité culturelle puisse servir de guide afin de déconstruire le racisme systémique envers les Autochtones présent dans les sphères personnelles, professionnelles et historiques et que cela se reflète dans les soins de santé. Cette première étape, bien que personnelle, constitue une invitation à la profession infirmière à s’investir dans la lutte contre le racisme volontaire ou involontaire dans les soins de santé. En comprenant l’histoire canadienne, en nous engageant à nous allier, en plaidant pour la justice sociale, en prenant la parole activement et en intégrant des soins et des principes qui tiennent compte des traumatismes dans notre pratique, nous pouvons commencer à lutter efficacement contre le racisme systémique envers les Autochtones dans les soins de santé

    Addressing Indigenous-Specific Racism in Healthcare as Part of Reconciliation: A Nurses Responsibility to Mitigate Racism in Healthcare

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    Background: Reports of racism and discrimination, particularly Indigenous-specific racism within the Canadian health care system, has become common in the news. The November 2020 report entitled In Plain Sight: Addressing Indigenous-specific Racism and Discrimination in B. C. Health Care and the September 2020 death of Joyce Echaquan clearly indicate immediate action is required by all nurses to address current practice and to be accountable for delivering safe, competent, and ethical care to Indigenous peoples (First Nations, Métis, and Inuit). As a registered nurse and a white settler mother of two Indigenous sons, I cannot ignore Indigenous-specific racism. In alignment with the Truth and Reconciliation recommendations, I recognize the necessity to address the truth - the history of colonization in Canada and how it has affected and continues to affect Indigenous health and wellness. There are numerous publications that have described the legacy of both residential schools and the Indian hospitals, along with numerous anecdotal stories of the deplorable care provided to the First Peoples of Canada. This historical relationship has resulted in Indigenous peoples feeling deep mistrust towards the healthcare system. This sociopolitical history directly affects my Indigenous sons and their personal wellness as they navigate growing up in an environment of racism. Purpose: The purpose of this paper is to share with healthcare professionals the effects Indigenous-specific racism has on Canadian Indigenous people with the hope of fostering more authentic conversations to guide policy change and create an environment for safe, competent, compassionate, and ethical healthcare delivery. Implications: It is necessary for all health care providers to engage in safe, compassionate, competent, and ethical care for all patients. Practicing cultural safety an important first step when engaging with Indigenous peoples. This colonial history impacts my sons’ wellness and I have prepared a letter to share with them and my nursing colleagues. My hope is twofold: 1) that they will keep this letter and read it as they face unnecessary challenges simply because they are Indigenous; and secondly, the nursing profession will address and eliminate Indigenous-specific racism in healthcare.&nbsp

    Role of the IL-33/ST2 axis in cardiovascular disease: A systematic review and meta-analysis.

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    Funder: National Institute of Health Research Cambridge Biomedical Research CentreFunder: AstraZenecaFunder: Cambridge University Hospitals NHS Foundation TrustFunder: British Heart FoundationFunder: National Institute for Health Research (NIHR)UNLABELLED: Interleukin (IL)-33 and its unique receptor, ST2, play a pivotal role in the immune response to infection and stress. However, there have been conflicting reports of the role of IL-33 in cardiovascular disease (CVD) and the potential of this axis in differentiating CVD patients and controls and with CVD disease severity, remains unclear. AIMS: 1) To quantify differences in circulating IL-33 and/or sST2 levels between CVD patients versus controls. 2) Determine association of these biomarkers with mortality in CVD and community cohorts. METHODS AND RESULTS: Using Pubmed/MEDLINE, Web of Science, Prospero and Cochrane databases, systematic review of studies published on IL-33 and/or sST2 levels in patients with CVD (heart failure, acute coronary syndrome, atrial fibrillation, stroke, coronary artery disease and hypertension) vs controls, and in cohorts of each CVD subtype was performed. Pooled standardised mean difference (SMD) of biomarker levels between CVD-cases versus controls and hazard ratios (HRs) for risk of mortality during follow-up in CVD patients, were assessed by random effects meta-analyses. Heterogeneity was evaluated with random-effects meta-regressions. From 1071 studies screened, 77 were meta-analysed. IL-33 levels were lower in HF and CAD patients vs controls, however levels were higher in stroke patients compared controls [Meta-SMD 1.455, 95% CI 0.372-2.537; p = 0.008, I2 = 97.645]. Soluble ST2 had a stronger association with risk of all-cause mortality in ACS (Meta-multivariate HR 2.207, 95% CI 1.160-4.198; p = 0.016, I2 = 95.661) than risk of all-cause mortality in HF (Meta-multivariate HR 1.425, 95% CI 1.268-1.601; p<0.0001, I2 = 92.276). There were insufficient data to examine the association of IL-33 with clinical outcomes in CVD. CONCLUSIONS: IL-33 and sST2 levels differ between CVD patients and controls. Higher levels of sST2 are associated with increased mortality in individuals with CVD. Further study of IL-33/ST2 in cardiovascular studies is essential to progress diagnostic and therapeutic advances related to IL-33/ST2 signalling

    A novel silver bioactive glass elicits antimicrobial efficacy against Pseudomonas aeruginosa and Staphylococcus aureus in an ex vivo skin wound biofilm model

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    Biofilm infection is now understood to be a potent contributor to the recalcitrant nature of chronic wounds. Bacterial biofilms evade the host immune response and show increased resistance to antibiotics. Along with improvements in antibiotic stewardship, effective new anti-biofilm therapies are urgently needed for effective wound management. Previous studies have shown that bioactive glass (Bg) is able to promote healing with moderate bactericidal activity. Here we tested the antimicrobial efficacy of a novel BG incorporating silver (BgAg), against both planktonic and biofilm forms of the wound-relevant bacteria Pseudomonas aeruginosa and Staphylococcus aureus. BgAg was stable, long lasting, and potently effective against planktonic bacteria in time-kill assays (6-log reduction in bacterial viability within 2 h) and in agar diffusion assays. BgAg reduced bacterial load in a physiologically relevant ex vivo porcine wound biofilm model; P. aeruginosa (2-log reduction) and S. aureus (3-log reduction). BgAg also conferred strong effects against P. aeruginosa biofilm virulence, reducing both protease activity and virulence gene expression. Co-culture biofilms appeared more resistant to BgAg, where a selective reduction in S. aureus was observed. Finally, BgAg was shown to benefit the host response to biofilm infection, directly reducing host tissue cell death. Taken together, the findings provide evidence that BgAg elicits potent antimicrobial effects against planktonic and single-species biofilms, with beneficial effects on the host tissue response. Further investigations are required to elucidate the specific consequences of BG administration on polymicrobial biofilms, and further explore the effects on host–microbe interactions

    Comparing the effectiveness of polymer debriding devices using a porcine wound biofilm model

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    Objective: Debridement to remove necrotic and/or infected tissue and promote active healing remains a cornerstone of contemporary chronic wound management. While there has been a recent shift toward less invasive polymer-based debriding devices, their efficacy requires rigorous evaluation.Approach: This study was designed to directly compare monofilament debriding devices to traditional gauze using a wounded porcine skin biofilm model with standardized application parameters. Biofilm removal was determined using a surface viability assay, bacterial counts, histological assessment, and scanning electron microscopy (SEM).Results: Quantitative analysis revealed that monofilament debriding devices outperformed the standard gauze, resulting in up to 100-fold greater reduction in bacterial counts. Interestingly, histological and morphological analyses suggested that debridement not only removed bacteria, but also differentially disrupted the bacterially-derived extracellular polymeric substance. Finally, SEM of post-debridement monofilaments showed structural changes in attached bacteria, implying a negative impact on viability.Innovation: This is the first study to combine controlled and defined debridement application with a biologically relevant ex vivo biofilm model to directly compare monofilament debriding devices.Conclusion: These data support the use of monofilament debriding devices for the removal of established wound biofilms and suggest variable efficacy towards biofilms composed of different species of bacteria
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