Publications by authors named "Austen K"

Aim: To explore interventions employed to foster speaking-up behaviours of registered nurses (RNs) working in the care of older people.

Design: Scoping review.

Methods: The updated Joann Briggs Institute scoping review methodological guidelines were followed.

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Frontline workers for sexual and reproductive health and rights (SRHR) provide life-changing and life-saving services to millions of people every year. From accompanying the pregnant, delivering babies and caring for the newborn to supporting those subjected to sexual violence; from treating debilitating infections to expanding contraceptive choices; from enabling access to safe abortion services to countering homophobia: all over the world frontline SRHR carers and advocates make it possible for so many more to experience dignity in sex, sexuality and reproduction. Yet they are also subjected to hostility for what they do, for whom they provide care, for where they work and for the issues they address.

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Angiotensin-converting enzyme 2 (ACE2) is the central entry receptor for SARS-CoV-2. However, surprisingly little is known about the effects of host regulators on ACE2 localization, expression, and the associated influence on SARS-CoV-2 infection. Here we identify that ACE2 expression levels are regulated by the E3 ligase MDM2 and that MDM2 levels indirectly influence infection with SARS-CoV-2.

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Background & Aims: A single hepatitis B virus (HBV) particle is sufficient to establish chronic infection of the liver after intravenous injection, suggesting that the virus targets hepatocytes via a highly efficient transport pathway. We therefore investigated whether HBV uses a physiological liver-directed pathway that supports specific host-cell targeting in vivo.

Methods: We established the ex vivo perfusion of intact human liver tissue that recapitulates the liver physiology to investigate HBV liver targeting.

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(1) The project "Tatort Streetlight" implements an insect-friendly road light design in a four year before-after, control-impact (BACI) approach involving citizen scientists. It will broaden the stakeholder interests from solely anthropogenic perspectives to include the welfare of insects and ecosystems. Motivated by the detrimental impacts of road lighting systems on insects, the project aims to find solutions to reduce the insect attraction and habitat fragmentation resulting from roadway illumination.

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In this pilot study, microplastic beads (5-50 μm) were tagged with fluorescent dye and introduced to the soil of potted Betula pendula Roth. (silver birch) saplings during the growing season. After five months, root samples were examined using fluorescence- and confocal laser scanning microscopy.

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Aims And Objectives: To identify common themes about care failures in residential aged care as described from the perspectives of older people and their families in transcripts from hearings and submission to the Australian Royal Commission. These failures are explored through the lens of moral disengagement.

Background: Previous inquiries into care failures have highlighted widespread harm from inhumane care, caused by staff carelessness, indifference and callousness.

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Acute and chronic itch are burdensome manifestations of skin pathologies including allergic skin diseases and atopic dermatitis, but the underlying molecular mechanisms are not well understood. Cysteinyl leukotrienes (CysLTs), comprising LTC, LTD, and LTE, are produced by immune cells during type 2 inflammation. Here, we uncover a role for LTC and its signaling through the CysLT receptor 2 (CysLTR) in itch.

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Article Synopsis
  • The American Initiative in Mast Cell Diseases (AIM) held its first conference at Stanford in May 2019 to form a Pan-American organization of experts in mast cell diseases.
  • AIM aims to create a collaborative network for researchers to enhance diagnostics, understand mast cell biology, and develop new therapies.
  • The proceedings address topics like hereditary alpha-tryptasemia, mast cell activation syndromes, and the diversity of mastocytosis, while also seeking international cooperation, particularly with the European Competence Network on Mastocytosis.
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Murine mast cells (MCs) contain two lineages: inducible bone marrow-derived mucosal MCs (MMCs) and constitutive embryonic-derived connective tissue MCs (CTMCs). Here, we use RNA sequencing, flow cytometry, and genetic deletion in two allergic lung inflammation models to define these two lineages. We found that inducible MCs, marked by β7 integrin expression, are highly distinct from airway CTMCs at rest and during inflammation and unaffected by targeted CTMC deletion.

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The origin and functions of mast cells (MCs) have been debated since their description by Paul Ehrlich in 1879. MCs have long been considered 'reactive bystanders' and 'amplifiers' in inflammatory processes, allergic reactions, and host responses to infectious diseases. However, knowledge about the origin, phenotypes and functions of MCs has increased substantially over the past 50 years.

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Our current recommendations for diagnosing and treating primary mast cell (MC) activation syndrome make use of the latest studies and consensus guidelines for clinically recognizing systemic anaphylaxis in real time, regardless of whether allergen-triggered or other pathways are involved; our current understanding of the biomarkers secreted by activated MCs that best discriminate this disorder from other conditions; and the therapeutic drugs that might selectively affect those mediators or MCs themselves. Finding familial or somatic mutations of genes that cause MCs to be hyperactivatable would extend our diagnostic tools and potentially indicate new therapeutic interventions, targeting either the mutated gene product or the associated molecular pathway. In conclusion, we trust that the clinical, laboratory, and therapeutic criteria for primary MC activation syndromes described herein will provide clinicians with practical criteria of sufficient sensitivity and specificity to diagnose most cases without overdiagnosing the disorder in patients who likely have other conditions.

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The cysteinyl leukotrienes (cys-LTs), leukotriene C, (LTC), LTD, and LTE, are lipid mediators of inflammation. LTC is the only intracellularly synthesized cys-LT through the 5-lipoxygenase and LTC synthase pathway and after transport is metabolized to LTD and LTE by specific extracellular peptidases. Each cys-LT has a preferred functional receptor in vivo; LTD to the type 1 cys-LT receptor (CysLTR), LTC to CysLTR, and LTE to CysLTR (OXGR1 or GPR99).

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Mast cell (MC) mediator release after crosslinking of surface-bound IgE antibody by ingested antigen underlies food allergy. However, IgE antibodies are not uniformly associated with food allergy, and intestinal MC load is an important determinant. Atopic dermatitis (AD), characterized by pruritis and cutaneous sensitization to allergens, including foods, is strongly associated with food allergy.

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Cysteinyl leukotrienes (cys-LTs) are proinflammatory mediators that enhance vascular permeability through distinct receptors (CysLTRs). We found that CysLTR regulates angiogenesis in isolated mouse endothelial cells (ECs) and in Matrigel implants in WT mice and enhances EC contraction and permeability via the Rho-dependent myosin light chain 2 and vascular endothelial (VE)-cadherin axis. Since solid tumors utilize aberrant angiogenesis for their growth and metastasis and their vessels exhibit vascular hyperpermeability, we hypothesized that CysLTR, via its actions on the endothelium, might regulate tumor growth.

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Mastocytosis is a term used to denote a heterogeneous group of conditions defined by the expansion and accumulation of clonal (neoplastic) tissue mast cells in various organs. The classification of the World Health Organization (WHO) divides the disease into cutaneous mastocytosis, systemic mastocytosis, and localized mast cell tumors. On the basis of histomorphologic criteria, clinical parameters, and organ involvement, systemic mastocytosis is further divided into indolent systemic mastocytosis and advanced systemic mastocytosis variants, including aggressive systemic mastocytosis and mast cell leukemia.

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Group 2 innate lymphoid cells (ILC2s) and type 2 helper T cells (Th2 cells) are the primary source of interleukin 5 (IL-5) and IL-13 during type 2 (allergic) inflammation in the lung. In Th2 cells, T cell receptor (TCR) signaling activates the transcription factors nuclear factor of activated T cells (NFAT), nuclear factor κB (NF-κB), and activator protein 1 (AP-1) to induce type 2 cytokines. ILC2s lack a TCR and respond instead to locally produced cytokines such as IL-33.

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The bronchoconstrictive and proinflammatory properties of cysteinyl leukotrienes (cysLTs) in allergic asthma mediate their effects predominantly through the cysLT1 receptor (cysLT1R). However, the role of cysLTs and cysLT1R in innate immune-triggered asthma is largely unexplored. We explored the synthesis of cysLTs and cysLT1R as determinants of airway responses in an oxidative stress-induced model of irritant asthma.

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Cysteinyl leukotrienes (cysLTs), leukotriene C4 (LTC4), LTD4, and LTE4 are proinflammatory lipid mediators with pathobiologic function in asthma. LTE4, the stable cysLT, is a weak agonist for the type 1 and type 2 cysLT receptors (CysLTRs), which constrict airway smooth muscle, but elicits airflow obstruction and pulmonary inflammation in patients with asthma. We recently identified GPR99 as a high-affinity receptor for LTE4 that mediates cutaneous vascular permeability.

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Mast cells are evolutionarily ancient sentinel cells. Like basophils, mast cells express the high-affinity receptor for immunoglobulin E (IgE) and have been linked to host defense and diverse immune-system-mediated diseases. To better characterize the function of these cells, we assessed the transcriptional profiles of mast cells isolated from peripheral connective tissues and basophils isolated from spleen and blood.

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