Partnership research with older people: moving towards making the rhetoric a reality

As nursing develops closer partnerships with older people in delivering care, it also needs to develop partnerships in order to create the knowledge base for practice in a way that challenges professional hegemony and empowers older people. However, the process of developing partnerships in research takes place against a background of academic research traditions and norms, which can present obstacles to collaboration. This paper is a reflection on the issues that have arisen in three projects where older people were involved in research at different levels, from sources of data to independent researchers. It points to some of the areas that need further exploration and development

Bloodstream form trypanosoma brucei depend upon multiple metacaspases associated with RAB11-positive endosomes

Trypanosoma brucei possesses five metacaspase genes. Of these, MCA2 and MCA3 are expressed only in the mammalian bloodstream form of the parasite, whereas MCA5 is expressed also in the insect procyclic form. Triple RNAi analysis showed MCA2, MCA3 and MCA5 to be essential in the bloodstream form, with parasites accumulating pre-cytokinesis. Nevertheless, triple null mutants (Δmca2/3Δmca5) could be isolated after sequential gene deletion. Thereafter, Δmca2/3Δmca5 mutants were found to grow well both in vitro in culture and in vivo in mice. We hypothesise that metacaspases are essential for bloodstream form parasites, but they have overlapping functions and their progressive loss can be compensated for by activation of alternative biochemical pathways. Analysis of Δmca2/3Δmca5 revealed no greater or lesser susceptibility to stresses reported to initiate programmed cell death, such as treatment with prostaglandin D2. The metacaspases were found to colocalise with RAB11, a marker for recycling endosomes. However, variant surface glycoprotein (VSG) recycling processes and the degradation of internalised anti-VSG antibody were found to occur similarly in wild type, Δmca2/3Δmca5 and triple RNAi induced parasites. Thus, the data provide no support for the direct involvement of T. brucei metacaspases in programmed cell death and suggest that the proteins have a function associated with RAB11 vesicles that is independent of known recycling processes of RAB11-positive endosomes

Pulmonary epithelium, cigarette smoke, and chronic obstructive pulmonary disease

Chronic obstructive pulmonary disease (COPD) is a complex chronic inflammatory disease involving a wide variety of cells and inflammatory mediators. The most important etiological factor in the development of this disease is cigarette smoking. Much of the research into the mechanisms of COPD has been concerned with the induction of inflammation and the role of neutrophils and macrophages in the pathophysiology of the disease. The possible contribution of the epithelium to the development of COPD has only recently become apparent and remains unclear. In this article we review research into the effect of cigarette smoke on the pulmonary epithelium with particular emphasis on oxidative stress, proteolytic load, pro-inflammatory cytokine and chemokine profile and epithelial secretions. In addition, we have also reviewed how cigarette smoke may affect epithelial damage and repair processes

Older people and research partnerships

Increasing consumer consultation is a priority for those involved in health and social care research and practice, with promoting greater public participation being widely accepted as 'a good thing' (Reason, 1994: 3). However, whilst such consultation may improve the quality of research and practice, there is a need to recognise the considerable investment of time and energy that is required for success (Baxter et al., 2001). Given the extra resources needed, it is important to understand how consultation and user involvement can work to benefit all parties. This paper describes our experiences of working together on a research project exploring people's involvement in decision-making processes when using care services in later life. When we started the project in March 2001 each of us could draw on a range of experiences that we hoped would make a valuable contribution. We have now worked together for over two years and this paper describes how our combined efforts have not only enhanced the overall quality of the research but also had personal benefits that we did not anticipate when we started ou

Using poems to explore the meaning of compassion to undergraduate nursing students

Background: Compassionate care provision is an integral part of nursing practice, but the ways in which pre-registration nurses are enabled to explore the concept are less well understood. Aim: The aim of this work was to consider how student nurses experience and understand compassion in the context of their education and clinical practice, using reflective poetry as a source of data. Method: This study drew on reflective poetry writing, underpinned by an interpretive phenomenological approach. Poems authored by study participants were analysed to explore how compassion is understood and experienced by pre-registration nursing students. Findings: Compassion was described and experienced by the students in many ways. It was discussed as a challenging aspect of practice, on an emotional and on a practical level. Feelings of vulnerability emerged through the data, often linked to the novice status of the students. Reflective poetry writing enabled students to write in a meaningful way about their thoughts and feelings, and offers educators a rich insight into the lifeworld of the student nurse. Conclusion: Compassion is a complex and multifaceted phenomenon that can be difficult for student nurses to engage with in real world practice settings. Creative ways of working, including the use of poetry, can offer student nurses, and those who support them, valuable help in understanding the challenges they encounter and identifying working practices that can make a positive contribution to nursing practice and associated education programmes. Implications for practice: Educators need to understand the meaning of compassion as it is lived by student nurses, in order to support their development Educators are required to develop their teaching practice to enable the exploration of thoughts and feelings about compassionate care provision Creative ways of teaching and learning can lead to a more unpredictable learning environment and ways to manage this need to be considered Poetry writing offers opportunities for educators to role model the personal behaviours expected of student nurses, as a way to help develop compassionate care provision

Detection of lipocortin 1 in human lung lavage fluid: lipocortin degradation as a possible proteolytic mechanism in the control of inflammatory mediators and inflammation.

Lipocortins are structurally related, glucocorticoid-inducible proteins that inhibit phospholipase A2 (PLA2), thereby reducing the liberation of arachidonic acid from phospholipids and so limiting the synthesis of eicosanoid inflammatory mediators. This study is the first demonstration of one lipocortin, lipocortin 1 (Lc 1; 37 kDa), in human lung lavage supernatants. In lavage fluid from healthy volunteers, a higher percentage (greater than 70%) of the detected Lc 1 was in its native form, compared to that from patients with abnormal lungs. In patients' lavage fluids, Lc 1 was more likely to be partially degraded (34 kDa). In abnormal bronchoalveolar lavage fluid (BALF), the more polymorphonuclear neutrophils (PMN)/lavage, the lower the proportion of Lc 1 in the native (37 kDa) form (n = 7 pairs, rs = -0.8214, p less than 0.05). Furthermore, when BALF cells were cultured and the harvested conditioned media incubated with pure human recombinant Lc 1, degradation of the 37 kDa form increased with the percentage of PMN (n = 10 pairs, s = -0.7200 after 1 hr; n = 6 pairs, rs = -0.9241 after 6 hr). These results suggest that factors released from the PMN are responsible for Lc 1 degradation in man. When recombinant human Lc 1 was incubated with human neutrophil elastase, the enzyme degraded Lc 1 in a dose-dependent way, suggesting that neutrophil elastase may be one such factor. Since PMNs are ubiquitous at sites of inflammation, it is possible that Lc 1 degradation is a permissive mechanism, which ensures that sufficient inflammation occurs to destroy the provocative stimulus. However, it is equally possible that, in some circumstances, the mechanism may be pathological and that the inactivation of Lc 1 leads to chronic, uncontrolled inflammation

A Global Plate Model Including Lithospheric Deformation Along Major Rifts and Orogens Since the Triassic

Global deep‐time plate motion models have traditionally followed a classical rigid plate approach, even though plate deformation is known to be significant. Here we present a global Mesozoic–Cenozoic deforming plate motion model that captures the progressive extension of all continental margins since the initiation of rifting within Pangea at ~240 Ma. The model also includes major failed continental rifts and compressional deformation along collision zones. The outlines and timing of regional deformation episodes are reconstructed from a wealth of published regional tectonic models and associated geological and geophysical data. We reconstruct absolute plate motions in a mantle reference frame with a joint global inversion using hot spot tracks for the last 80 million years and minimizing global trench migration velocities and net lithospheric rotation. In our optimized model, net rotation is consistently below 0.2°/Myr, and trench migration scatter is substantially reduced. Distributed plate deformation reaches a Mesozoic peak of 30 × 106 km2 in the Late Jurassic (~160–155 Ma), driven by a vast network of rift systems. After a mid‐Cretaceous drop in deformation, it reaches a high of 48 x 106 km2 in the Late Eocene (~35 Ma), driven by the progressive growth of plate collisions and the formation of new rift systems. About a third of the continental crustal area has been deformed since 240 Ma, partitioned roughly into 65% extension and 35% compression. This community plate model provides a framework for building detailed regional deforming plate networks and form a constraint for models of basin evolution and the plate‐mantle system

Pulmonary effects of inhalation of spark-generated silver nanoparticles in Brown-Norway and Sprague-Dawley rats

The increasing use of silver nanoparticles (AgNPs) in consumer products is concerning. We examined the potential toxic effects when inhaled in Brown-Norway (BN) rats with a pre-inflammatory state compared to Sprague-Dawley (SD) rats.We determined the effect of AgNPs generated from a spark generator (mass concentration: 600-800 μg/mm(3); mean diameter: 13-16 nm; total lung doses: 8 [Low] and 26-28 [High] μg) inhaled by the nasal route in both rat strains. Rats were sacrificed at day 1 and day 7 after exposure and measurement of lung function.In both strains, there was an increase in neutrophils in bronchoalveolar lavage (BAL) fluid at 24 h at the high dose, with concomitant eosinophilia in BN rats. While BAL inflammatory cells were mostly normalised by Day 7, lung inflammation scores remained increased although not the tissue eosinophil scores. Total protein levels were elevated at both lung doses in both strains. There was an increase in BAL IL-1β, KC, IL-17, CCL2 and CCL3 levels in both strains at Day 1, mostly at high dose. Phospholipid levels were increased at the high dose in SD rats at Day 1 and 7, while in BN rats, this was only seen at Day 1; surfactant protein D levels decreased at day 7 at the high dose in SD rats, but was increased at Day 1 at the low dose in BN rats. There was a transient increase in central airway resistance and in tissue elastance in BN rats at Day 1 but not in SD rats. Positive silver-staining was seen particularly in lung tissue macrophages in a dose and time-dependent response in both strains, maximal by day 7. Lung silver levels were relatively higher in BN rat and present at day 7 in both strains.Presence of cellular inflammation and increasing silver-positive macrophages in lungs at day 7, associated with significant levels of lung silver indicate that lung toxicity is persistent even with the absence of airway luminal inflammation at that time-point. The higher levels and persistence of lung silver in BN rats may be due to the pre-existing inflammatory state of the lungs

Patient and Public Involvement (PPI) report for proposed study: Listen and Learn

Context: Patient and Public Involvement (PPI) work was undertaken to engage relevant stakeholders (residents, family members, volunteers and staff) in order to incorporate their experiences and insights into our NIHR grant proposal, “Listen and learn”. The proposed research study aims to explore the use of resident feedback in care homes to embolden person-centred care. NIHR RDS formally funded PPI activity in the NW throughout the summer of 2016. Using similar methods, researchers from project teams across the UK also informally engaged with residents, care managers, volunteers and family members in their networks to provide perspectives from across the UK. This report focuses on the NW engagement but is reflective of the wider, informal engagements. Aims: The PPI activity was undertaken in order to learn from older people, their formal carers and families/relatives: 1. The relevance to them of the proposed research question 2. How best to attract, recruit and retain people as research participants 3. Identification of ethical issues and concerns 4. How best to support staff and volunteers during research 5. How best to communicate the difference (impact) our project makes People told us: 1.Volunteers are scarce, so need to scope availability. For volunteers, safeguarding and capacity to speak up about concerns deemed important. Settings will require bespoke engagement approaches. 2.Methods should be mixed, e.g. visual/diaries; non-verbal communication/diversity addressed, e.g. people with dementia need a skilled approach; sufficient time to develop rapport. 3.Impacts to focus on people, not only institutions; sufficient time needed to show impact. Dissemination should consider adjustments for people with disabilities to enable involvement. (Full report available via MMU e-repository

A unique Kelch domain phosphatase in Plasmodium regulates ookinete morphology, motility and invasion

Signalling through post-translational modification (PTM) of proteins is a process central to cell homeostasis, development and responses to external stimuli. The best characterised PTM is protein phosphorylation which is reversibly catalysed at specific residues through the action of protein kinases (addition) and phosphatases (removal). Here, we report characterisation of an orphan protein phosphatase that possesses a domain architecture previously only described in Plantae. Through gene disruption and the production of active site mutants, the enzymatically active Protein Phosphatase containing Kelch-Like domains (PPKL, PBANKA_132950) is shown to play an essential role in the development of an infectious ookinete. PPKL is produced in schizonts and female gametocytes, is maternally inherited where its absence leads to the development of a malformed, immotile, non-infectious ookinete with an extended apical protrusion. The distribution of PPKL includes focussed localization at the ookinete apical tip implying a link between its activity and the correct deployment of the apical complex and microtubule cytoskeleton. Unlike wild type parasites, ppkl(-) ookinetes do not have a pronounced apical distribution of their micronemes yet secretion of microneme cargo is unaffected in the mutant implying that release of microneme cargo is either highly efficient at the malformed apical prominence or secretion may also occur from other points of the parasite, possibly the pellicular pores