An analysis of time conceptualisations and good care in an acute hospital setting.

This study articulates the relationship between conceptualisations of time and the accounts of good care in an acute setting. Neoliberal healthcare services, with their focus on efficiencies, predominantly calculate quality care based on time-on-the-clock workforce management planning systems. However, the ways staff conceptualise and then relate to diverse meanings of time have implications for good care and for staff morale. This phenomenological study was undertaken in acute medical-surgical wards, investigating the contextual, temporal nature of care embedded in human relations. The study interviews involved 17 participants: 11 staff, 3 previous patients and 3 family members. Data were analysed iteratively to surface the phenomenality of temporality and good care. The following constituents of the data set are explored that together illustrate the relationship between the conceptualisations of time and the accounts of good care in an acute setting: patient time as a relational journey; patient time, sovereign time and time ethics and time, teamwork and flow. The findings are clinically significant because they offer a contrasting narrative about the relationship between time and care quality. The experiences of giving and receiving good care are indivisible from how temporality is experienced and the social relations within which care is embedded. Healthcare staff experience temporality differently from patients and families, a point that healthcare participants in this study appeared to comprehend and accommodate. For all parties involved in providing care or being the recipient of care, however, the capacity to be present was valued as a humanising ethic of care. Our study reinforces the importance of not creating presumptive binaries about which temporal structures are more or less humanising-there is a place for a fast-paced tempo, which can be experienced as being in the flow of human relations with one's team and on behalf of patients.

A Heideggerian analysis of good care in an acute hospital setting: Insights from healthcare workers, patients and families.

This study articulates the relational constituents of good care beyond techno-rational competence. Neoliberal healthcare means that notions of care are readily commodified and reduced to quantifiable assessments and checklists. This novel research investigated accounts of good care provided by nursing, medical, allied and auxiliary staff. The Heideggerian phenomenological study was undertaken in acute medical-surgical wards, investigating the contextual, communicative nature of care. The study involved interviews with 17 participants: 3 previous patients, 3 family members and 11 staff. Data were analysed iteratively, dwelling with stories and writing and rewriting to surface the phenomenality of good care. The data set highlighted the following essential constituents: authentic care: caring encompassing solicitude (fürsorge); impromptu care: caring beyond role category; sustained care: caring beyond specialist parameters; attuned care: caring encompassing family and culture; and insightful care: caring beyond assessment and diagnosis. The findings are clinically significant because they indicate the importance of nurse leaders and educators harnessing the potential capacity of all healthcare workers to participate in good care. Healthcare workers reported that participating in or witnessing good care was uplifting and added meaning to their work, contributing to a sense of shared humanity.

Integration of JAK/STAT receptor-ligand trafficking, signalling and gene expression in Drosophila melanogaster cells.

The JAK/STAT pathway is an essential signalling cascade required for multiple processes during development and for adult homeostasis. A key question in understanding this pathway is how it is regulated in different cell contexts. Here, we have examined how endocytic processing contributes to signalling by the single cytokine receptor in Drosophila melanogaster cells, Domeless. We identify an evolutionarily conserved di-leucine (di-Leu) motif that is required for Domeless internalisation and show that endocytosis is required for activation of a subset of Domeless targets. Our data indicate that endocytosis both qualitatively and quantitatively regulates Domeless signalling. STAT92E, the single STAT transcription factor in Drosophila, appears to be the target of endocytic regulation, and our studies show that phosphorylation of STAT92E on Tyr704, although necessary, is not always sufficient for target transcription. Finally, we identify a conserved residue, Thr702, which is essential for Tyr704 phosphorylation. Taken together, our findings identify previously unknown aspects of JAK/STAT pathway regulation likely to play key roles in the spatial and temporal regulation of signalling in vivo.

A 3D Renal Proximal Tubule on Chip Model Phenocopies Lowe Syndrome and Dent II Disease Tubulopathy.

Lowe syndrome and Dent II disease are X-linked monogenetic diseases characterised by a renal reabsorption defect in the proximal tubules and caused by mutations in the OCRL gene, which codes for an inositol-5-phosphatase. The life expectancy of patients suffering from Lowe syndrome is largely reduced because of the development of chronic kidney disease and related complications. There is a need for physiological human in vitro models for Lowe syndrome/Dent II disease to study the underpinning disease mechanisms and to identify and characterise potential drugs and drug targets. Here, we describe a proximal tubule organ on chip model combining a 3D tubule architecture with fluid flow shear stress that phenocopies hallmarks of Lowe syndrome/Dent II disease. We demonstrate the high suitability of our in vitro model for drug target validation. Furthermore, using this model, we demonstrate that proximal tubule cells lacking OCRL expression upregulate markers typical for epithelial-mesenchymal transition (EMT), including the transcription factor SNAI2/Slug, and show increased collagen expression and deposition, which potentially contributes to interstitial fibrosis and disease progression as observed in Lowe syndrome and Dent II disease.

Reading Heidegger.

Heidegger's philosophy is a significant contribution to understanding the meaning of lived experience. Recognizing this, nurses and other health professionals have taken on the research approach of Heideggerian hermeneutic phenomenology. This requires reading the writing of Heidegger. Philosophers themselves acknowledge this writing is dense, difficult to grasp, uses language for which there is no easy translation, and leaves the reader with more questions than answers. Drawing on commentary from philosophers who seek to read Heidegger and from a research study which interviewed doctoral students who were "reading Heidegger," we seek to show the nature of the experience of pursuing such a challenging quest.

Heideggerian phenomenological hermeneutics: Working with the data.

It is one thing to read about the methodology and methods of Heideggerian hermeneutic phenomenological research, the ontic description. It is quite another thing to be faced with an interview transcript. This article draws on a study that asked doctoral students about their experience of doing such research. How did they become "phenomenological/hermeneutic" in their thinking and writing? What helped them to find their way? We offer this article as a means of letting others learn from our own experiences. We support our insights with the writings of Heidegger and Gadamer to show the methodological congruence that is essential to Heideggerian phenomenological hermeneutic research.

Interplay of Endocytosis and Growth Factor Receptor Signalling.

Growth factor receptors play a variety of roles during embryonic development and in adult homeostasis. These receptors are activated repeatedly in different cellular contexts and with different cellular outcomes. This begs the question as to how cells in a particular developmental, spatial and temporal context, or in adult tissue, interpret signalling by growth factor receptors in order to deliver qualitatively different signalling outputs. One mechanism by which this could occur is via endocytic regulation. The original paradigm for the role of endocytosis in growth factor receptor signalling was that receptor uptake has a quantitative role in signalling by reducing the number of cell surface receptors available for activation and targeting activated receptors for degradation. However, a range of studies over the last several years, in many different experimental systems, has demonstrated an additional qualitative role for endocytic trafficking in receptor signalling, with specific outcomes depending on the location of the signalling complex. Confinement of receptors within endosomes can spatially regulate signalling, facilitating specific protein interactions or post-translational modifications that alter throughout the trafficking process. Therefore, endocytosis does not simply regulate cell surface expression, but tightly controls protein interactions and function to produce distinct outcomes.

Bioinspired self-repairing slippery surfaces with pressure-stable omniphobicity.

Creating a robust synthetic surface that repels various liquids would have broad technological implications for areas ranging from biomedical devices and fuel transport to architecture but has proved extremely challenging. Inspirations from natural nonwetting structures, particularly the leaves of the lotus, have led to the development of liquid-repellent microtextured surfaces that rely on the formation of a stable air-liquid interface. Despite over a decade of intense research, these surfaces are, however, still plagued with problems that restrict their practical applications: limited oleophobicity with high contact angle hysteresis, failure under pressure and upon physical damage, inability to self-heal and high production cost. To address these challenges, here we report a strategy to create self-healing, slippery liquid-infused porous surface(s) (SLIPS) with exceptional liquid- and ice-repellency, pressure stability and enhanced optical transparency. Our approach-inspired by Nepenthes pitcher plants-is conceptually different from the lotus effect, because we use nano/microstructured substrates to lock in place the infused lubricating fluid. We define the requirements for which the lubricant forms a stable, defect-free and inert 'slippery' interface. This surface outperforms its natural counterparts and state-of-the-art synthetic liquid-repellent surfaces in its capability to repel various simple and complex liquids (water, hydrocarbons, crude oil and blood), maintain low contact angle hysteresis (<2.5°), quickly restore liquid-repellency after physical damage (within 0.1-1 s), resist ice adhesion, and function at high pressures (up to about 680 atm). We show that these properties are insensitive to the precise geometry of the underlying substrate, making our approach applicable to various inexpensive, low-surface-energy structured materials (such as porous Teflon membrane). We envision that these slippery surfaces will be useful in fluid handling and transportation, optical sensing, medicine, and as self-cleaning and anti-fouling materials operating in extreme environments.

Systems dynamics in endocytosis.

The endocytic system acts at the crossroads of different cellular activities to play a central role in the regulation of cell signaling and membrane dynamics. An European Molecular Biology Organization (EMBO) conference held in October 2013 in Villars-sur-Ollon gathered researchers from all over the world to present their latest findings on the endolysosomal system and identify major challenges for the future. The conference covered the entire spectrum of research in this rapidly evolving field ranging from the cellular mechanics of endocytosis to the role of proteins and lipids in the biogenesis and function of endolysosomal organelles and the analysis of higher order system properties in multicellular contexts. In particular, the meeting highlighted current efforts to complement the insights that can be gained by biochemical and cell biological approaches with the use of quantitative biophysics, systems biology and animal model systems to achieve an integrated view of the properties of the endomembrane system and its role in cellular information processing.

Open, trusting relationships underpin safety in rural maternity a hermeneutic phenomenology study.

BACKGROUND: There are interwoven personal, professional and organisational relationships to be navigated in maternity in all regions. In rural regions relationships are integral to safe maternity care. Yet there is a paucity of research on how relationships influence safety and nurture satisfying experiences for rural maternity care providers and mothers and families in these regions. This paper draws attention to how these relationships matter. METHODS: This research is informed by hermeneutic phenomenology drawing on Heidegger and Gadamer. Thirteen participants were recruited via purposeful sampling and asked to share their experiences of rural maternity care in recorded unstructured in-depth interviews. Participants were women and health care providers living and working in rural regions. Recordings were transcribed and data interpretively analysed until a plausible and trustworthy thematic pattern emerged. RESULTS: Throughout the data the relational nature of rural living surfaced as an interweaving tapestry of connectivity. Relationships in rural maternity are revealed in myriad ways: for some optimal relationships, for others feeling isolated, living with discord and professional disharmony. Professional misunderstandings undermine relationships. Rural maternity can become unsustainable and unsettling when relationships break down leading to unsafeness. CONCLUSIONS: This study reveals how relationships are an important and vital aspect to the lived-experience of rural maternity care. Relationships are founded on mutual understanding and attuned to trust matter. These relationships are forged over time and keep childbirth safe and enable maternity care providers to work sustainably. Yet hidden unspoken pre-understandings of individuals and groups build tension in relationships leading to discord. Trust builds healthy rural communities of practice within which everyone can flourish, feel accepted, supported and safe. This is facilitated by collaborative learning activities and open respectful communication founded on what matters most (safe positive childbirth) whilst appreciating and acknowledging professional and personal differences.

Hermeneutics and pragmatism offer a way of exploring the consequences of advanced assessment.

Linking specific nursing actions to outcomes in the healthcare setting is challenging. Patient outcomes are varied and influenced by a myriad of factors, and always involve a wider team than any one nurse. It is difficult to control for a single action or set of actions of a particular nurse. Furthermore, practice is seldom about any 'one' action, for one thing leads to another, all within a complex interplay of influencing factors. In this article, we outline a research method which combined Dewey's pragmatism with Gadamer's hermeneutics to explore the consequences of the nurse's use of advanced assessment skills in the acute care setting of medical and surgical wards. This pragmatic hermeneutic methodological approach allowed the complex interplay of influences to be revealed in the unfolding story. Reflection of the nurse brought insights that may otherwise have been passed over. The philosophical notions of Dewey drew attention to the play of 'means' and 'ends'. A hermeneutic approach that calls for 'thinking' extends understanding and raises insights that can inform education and practice.

Revealing tact within postnatal care.

In this article, we explore the nature of good postnatal care through a hermeneutic unpacking of the notion of tact, drawing on the philosophical writings of Heidegger, Gadamer, and van Manen. The tactful encounters considered were from a hermeneutic research study within a small, rural birthing center in New Zealand. Insights drawn from the analysis were as follows: the openness of listening, watching and being attuned that builds a positive mode of engagement, recognizing that the distance the woman needs from her nurse/midwife is a call of tact, that tact is underpinned by a spirit of care, within tact there are moods and tact might require firmness, and that all of these factors come together to build trust. We conclude that the attunement of tact requires that the staff member has time to spend with a woman, enough energy to engage, and a spirit of care. Women know that tactful practice builds their confidence and affects their mothering experience. Tact cannot be assumed; it needs to be nurtured and sheltered.

Occupational therapy's oversight: How science veiled our humanity.

BACKGROUND: Occupational therapy's connection to positivist science predates the profession's formal beginning, with important contributing knowledge sources coming from mathematics, physics, psychology, and systems theory. While these sources of objective knowledge provide a rational, defendable position for practice, they can only explain a portion of what it means to exist as an occupational being. AIMS/OBJECTIVES: This article aims to reveal some of the history of science within occupational therapy and reveal the subjective, ontological nature of doing everyday activities that the profession's preoccupation with positivist science has obscured. METHODS: This research used a history of ideas methodology to uncover how occupational therapy perceived people and how practice was conceptualised and conducted between 1800 and 1980s, as depicted in writing of the time. CONCLUSION: Analysis showed that, through history, people were increasingly categorised and delimited. Practice also became systematically controlled, moving occupational therapy into a theoretical, scientific, and abstract realm. SIGNIFICANCE: The emphasis placed on objectivity diminishes the attention given to human ways of practicing, where the subjective experience is central to our thinking.

TAG1 regulates the endocytic trafficking and signaling of the semaphorin3A receptor complex.

Endocytic trafficking of membrane proteins is essential for neuronal structure and function. We show that Transient Axonal Glycoprotein 1 (TAG1 or CNTN2), a contactin-related adhesion molecule, plays a central role in the differential trafficking of components of the semaphorin3A (Sema3A) receptor complex into distinct endosomal compartments in murine spinal sensory neuron growth cones. The semaphorin3A receptor is composed of Neuropilin1 (NRP1), PlexinA4, and L1, with NRP1 being the ligand-binding component. TAG1 interacts with NRP1, causing a change in its association with L1 in the Sema3A response such that L1 is lost from the complex following Sema3A binding. Initially, however, L1 and NRP1 endocytose together and only become separated intracellularly, with NRP1 becoming associated with endosomes enriched in lipid rafts and colocalizing with TAG1 and PlexinA4. When TAG1 is missing, NRP1 and L1 fail to separate and NRP1 does not become raft associated; colocalization with PlexinA4 is reduced and Plexin signaling is not initiated. These observations identify a novel role for TAG1 in modulating the intracellular sorting of signaling receptor complexes.

Negative regulation of Drosophila JAK-STAT signalling by endocytic trafficking.

Appropriate regulation of signal transduction pathways is essential for normal development and is often disrupted in disease. Therefore, many regulatory mechanisms and feedback loops have evolved to ensure appropriate signalling. One mechanism previously suggested to modulate a range of signal transduction pathways involves the internalisation and destruction of transmembrane receptors by the endocytic trafficking machinery. Strikingly, a recent report has suggested that the endocytic trafficking of the Drosophila JAK-STAT pathway receptor Domeless (Dome) does not act to downregulate pathway activity, but rather is necessary for in vivo signalling. Here, we examine this relationship to address the interaction of Drosophila JAK-STAT pathway signalling and endocytic trafficking. We show that Dome is trafficked through clathrin-mediated endocytosis and a directed RNAi screen identified several components of the endocytic machinery as negative regulators of pathway signalling. We demonstrate that Dome signals both from the plasma membrane and internalised vesicles and show, using knockdown experiments, that endocytic components negatively regulate JAK-STAT signalling in vivo. As such, disruption in endocytic trafficking represents a potent negative regulator of the disease relevant JAK-STAT signalling cascade.

Clathrin coated pits as signaling platforms for Akt signaling.

Signaling by the activated epidermal growth factor receptor (EGFR) results in diverse cell fates. In this issue, Cabral-Dias et al. (2022. J. Cell Biol.https://doi.org/10.1083/jcb.201808181) demonstrate how plasma membrane clathrin coated pits can act as a signaling platform for one branch of EGFR downstream signaling.

Doing everyday occupations both conceals and reveals the phenomenon of being aged.

BACKGROUND/AIM: The phenomenon of ageing is so commonplace that it is ordinarily taken-for-granted, with little call to question its meaning. Of importance to occupational therapists is the recent appeal to understand older adults' ordinary ways of everyday living. The aim of this interpretive phenomenological study was to understand the meaning of 'being aged' through the everyday experiences of those who are long-lived. METHODS: The writings of two philosophers, Hans-Georg Gadamer and Martin Heidegger, guided the study's design and research methods. Being aged in the context of everyday living was the phenomenon of interest. Individual interviews were conducted with 15 community-dwelling New Zealand elders: four Maori aged 71-93 years and 11 non-Maori aged 80-97 years. Stories of going about daily occupations and particular moments in the day were elicited during conversational-style interviews. Hermeneutic methods and phenomenological reflection were used to analyse the data. RESULTS: Two overarching notions were illuminated. The ordinary ways of 'being in the every day', such as having a routine and a familiar purposefulness, conceal being aged. In contrast, 'experiencing the unaccustomed', such as suddenly noticing an unaccustomed weakness or oldness, in the midst of doing deeply familiar occupations is an announcing of being aged. CONCLUSIONS and SIGNIFICANCE OF THE STUDY: As such, engaging in everyday, familiar occupations holds the potential to both conceal and reveal the phenomenon of being aged. These results point to the importance of illuminating the lived experience of occupational engagement as a fruitful way of informing occupation-focussed practice.

A phosphatidylserine species inhibits a range of TLR- but not IL-1beta-induced inflammatory responses by disruption of membrane microdomains.

TLRs detect conserved molecular patterns that are unique to microbes, enabling tailored responses to invading pathogens and modulating a multitude of immunopathological conditions. We investigated the ability of a naturally occurring stearoyl-arachidonoyl form of phosphatidylserine (SAPS) to inhibit the proinflammatory effects of TLR agonists in models of inflammation investigating the interaction of leukocytes with epithelial and endothelial cells. The responses to LPS of both epithelial and endothelial cells were highly amplified in the presence of PBMCs. Coincubation with SAPS markedly inhibited activation of cocultures by LPS, principally through inhibition of the TLR4 signaling pathway in PBMCs; however, this was not through downmodulation of TLR4 or coreceptor expression, nor was IL-1beta-induced cytokine release affected. SAPS also impaired Pam(3)CSK(4) (TLR2/1), Gardiquimod (TLR7/8), and Streptococcus pneumoniae-induced cytokine release, but had only modest effects on poly(I:C) (TLR3)-induced responses. Fluorescence resonance energy transfer analysis of molecular associations revealed that SAPS disrupted the association of both TLR4 and TLR2 with their respective membrane partners that are required for signaling. Thus, our data reinforce the existence and importance of cooperative networks of TLRs, tissue cells, and leukocytes in mediating innate immunity, and identify a novel disrupter of membrane microdomains, revealing the dependence of TLR signaling on localization within these domains.

Functions of actin in endocytosis.

Endocytosis is a fundamental eukaryotic process required for remodelling plasma-membrane lipids and protein to ensure appropriate membrane composition. Increasing evidence from a number of cell types reveals that actin plays an active, and often essential, role at key endocytic stages. Much of our current mechanistic understanding of the endocytic process has come from studies in budding yeast and has been facilitated by yeast's genetic amenability and by technological advances in live cell imaging. While endocytosis in metazoans is likely to be subject to a greater array of regulatory signals, recent reports indicate that spatiotemporal aspects of vesicle formation requiring actin are likely to be conserved across eukaryotic evolution. In this review we focus on the 'modular' model of endocytosis in yeast before highlighting comparisons with other cell types. Our discussion is limited to endocytosis involving clathrin as other types of endocytosis have not been demonstrated in yeast.