Synthetic metabolons for metabolic engineering.

Journal ArticleResearch Support, Non-U.S. Gov'tReviewThis is a pre-copyedited, author-produced PDF of an article accepted for publication in Journal of Experimental Botany following peer review. The definitive publisher-authenticated version J. Exp. Bot. (2014) 65 (8) pp. 1947-1954 is available online at: http://jxb.oxfordjournals.org/content/65/8/1947It has been proposed that enzymes can associate into complexes (metabolons) that increase the efficiency of metabolic pathways by channelling substrates between enzymes. Metabolons may increase flux by increasing the local concentration of intermediates, decreasing the concentration of enzymes needed to maintain a given flux, directing the products of a pathway to a specific subcellular location or minimizing the escape of reactive intermediates. Metabolons can be formed by relatively loose non-covalent protein-protein interaction, anchorage to membranes, and (in bacteria) by encapsulation of enzymes in protein-coated microcompartments. Evidence that non-coated metabolons are effective at channelling substrates is scarce and difficult to obtain. In plants there is strong evidence that small proportions of glycolytic enzymes are associated with the outside of mitochondria and are effective in substrate channelling. More recently, synthetic metabolons, in which enzymes are scaffolded to synthetic proteins or nucleic acids, have been expressed in microorganisms and these provide evidence that scaffolded enzymes are more effective than free enzymes for metabolic engineering. This provides experimental evidence that metabolons may have a general advantage and opens the way to improving the outcome of metabolic engineering in plants by including synthetic metabolons in the toolbox

Heroism and paramedic practice: A constructivist metasynthesis of qualitative research

© 2022 Rees, Williams, Hogan, Smyth and Archer. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). https://creativecommons.org/licenses/by/4.0/Objectives: We aimed to identify, appraise, and synthesise the qualitative literature to develop theory on heroism and paramedic practice. Hypothesis/research question: What does published literature tell us about heroism and paramedic practice? Setting: Paramedics and other healthcare workers (HCWs) faced an outpouring of public support for them early in the COVID-19 pandemic which brought into focus the relationship between them and society, where they are portrayed as heroes. Participants: We conducted a metasynthesis using Evolved Grounded Theory and procedural guidelines of Noblit and Hare to guide analysis. Preferred Reporting Items for Systematic Reviews and Meta-analysis Protocols (PRISMA-P) guidelines were also applied. Results: 151 papers were retrieved and eleven included in the final sample. Studies were moderate to very low quality, involving a wide range of methodologies and settings; none specifically explored heroism and paramedic practice. The following interrelated themes were constructed on heroism and paramedic practice: (a) Myth, Folk law, and storytelling in heroism and paramedic practice (b) The epic journey of heroism and paramedic practice (c) Heroes and Zeroes: The fluctuating Societal Value in heroism and paramedic practice (d) Politicisation, and objectification in Heroism and Paramedic practice. Conclusion: Paramedics have long been characterised as heroes, but this may not reflect their everyday experiences. Heroism in paramedic practice can provide scripts for prosocial action, inspiring others, and leading to more social heroic actions. Paramedics may however be ambivalent to such heroism narratives, due to politicisation, and objectification in the media and society. This metasynthesis is only one of many possible constructions of heroism and paramedic practice and is the first point in making sense of and developing theory on heroism and paramedic practice. Study registration: PROSPERO: CRD42021234851.Peer reviewe

The dynamics of control of migrant agency workers: over-recruitment, "the bitchlist" and the enterprising-self

This article explores migrant workers’ experiences of organisational control while undertaking temporary agency work. This study is based on a ‘covert’ ethnographic study set at a temporary employment agency that short-term contracts workers to the catering and hospitality industry. The findings show how control is perceived by workers to emerge from the over-recruitment, coupled with the allocation of work through an informal ranking system. Migrant workers’ specific socio-economic circumstances and their race and gender identities informed their responses to these systems, resulting in the buy-in to discourses of enterprise. The result was actors who are complicit, if not active, participants in self and peer regulation. As such, this article contributes to the literature on enterprising-selves, control of temporary agency workers and the wider manufacturing consent literature

Characterizing aging in the human brainstem using quantitative multimodal MRI analysis.

Aging is ubiquitous to the human condition. The MRI correlates of healthy aging have been extensively investigated using a range of modalities, including volumetric MRI, quantitative MRI (qMRI), and diffusion tensor imaging. Despite this, the reported brainstem related changes remain sparse. This is, in part, due to the technical and methodological limitations in quantitatively assessing and statistically analyzing this region. By utilizing a new method of brainstem segmentation, a large cohort of 100 healthy adults were assessed in this study for the effects of aging within the human brainstem in vivo. Using qMRI, tensor-based morphometry (TBM), and voxel-based quantification (VBQ), the volumetric and quantitative changes across healthy adults between 19 and 75 years were characterized. In addition to the increased R2* in substantia nigra corresponding to increasing iron deposition with age, several novel findings were reported in the current study. These include selective volumetric loss of the brachium conjunctivum, with a corresponding decrease in magnetization transfer and increase in proton density (PD), accounting for the previously described “midbrain shrinkage.” Additionally, we found increases in R1 and PD in several pontine and medullary structures. We consider these changes in the context of well-characterized, functional age-related changes, and propose potential biophysical mechanisms. This study provides detailed quantitative analysis of the internal architecture of the brainstem and provides a baseline for further studies of neurodegenerative diseases that are characterized by early, pre-clinical involvement of the brainstem, such as Parkinson’s and Alzheimer’s diseases

How is poststroke fatigue understood by stroke survivors and carers? A thematic analysis of an online discussion forum.

OBJECTIVE: To understand poststroke fatigue from the perspective of stroke survivors and caregivers expressed in an online discussion forum. DESIGN: The search terms 'tiredness', 'fatigue', 'tired', 'weary' and 'weariness' were used to identify relevant posts. Thematic analysis performed by two independent researchers who coded all forum posts and identified pertinent themes. Posts were coded in relation to two research questions: (1) how is poststroke fatigue described? and (2) what coping strategies are suggested to target poststroke fatigue? Each theme was then summarised by a lead quotation in forum users' own words. SETTING: UK-based web forum hosted by Stroke Association, TalkStroke. Archives from 2004 to 2011 were accessed. PARTICIPANTS: 65 stroke survivors and caregivers (mean age 54 years, 61% female) contributed to 89 relevant posts that included a relevant search term. This included 38 stroke survivors, 23 individuals with family or carer role and 4 others unidentified. RESULTS: Six themes were generated: (1) medicalisation of poststroke fatigue: 'a classic poststroke symptom', (2) a tiredness unique to stroke: 'a legacy of stroke', (3) normalisation and acceptance of poststroke fatigue: 'part and parcel of stroke', (4) fighting the fatigue: 'an unwelcome guest', (5) survivors' and caregivers' biological explanations: 'the brain healing' and (6) coping mechanisms: 'pace yourself'. Forum users also repeatedly commented that poststroke fatigue was 'not understood by the profession'. CONCLUSION: This is the first study to employ data from an online forum to characterise poststroke fatigue. Our data are considered naturalistic owing to the absence of a researcher guiding the discussion and thus generates useful insights for healthcare professionals. Findings suggest a requirement for consistent understanding and explanation to be provided by healthcare professionals. The beliefs outlined here highlight the gap between clinical and community knowledge. Further research to translate understanding of patient and carer perspective into improved management of poststroke fatigue is required.This study was funded by the Malati Kanbur Studentship fund kindly donated by Ravi Kanbur and Margaret Grieco to Lucy Cavendish College, constituent college of the University of Cambridge. Jonathan Mant is an NIHR Senior Investigator. Views expressed in this written publication are those of the authors and not necessarily those of the funders

The Impact of Including Costs and Outcomes of Dementia in a Health Economic Model to Evaluate Lifestyle Interventions to Prevent Diabetes and Cardiovascular Disease.

OBJECTIVES: Economic evaluations of lifestyle interventions, which aim to prevent diabetes/cardiovascular disease (CVD), have not included dementia. Lifestyle interventions decrease dementia risk and extend life expectancy, leading to competing effects on health care costs. We aim to demonstrate the feasibility of including dementia in a public health cost-effectiveness analysis and quantify the overall impacts accounting for these competing effects. METHODS: The School for Public Health Research (SPHR) diabetes prevention model describes individuals' risk of type 2 diabetes, microvascular outcomes, CVD, congestive heart failure, cancer, osteoarthritis, depression, and mortality in England. In version 3.1, we adapted the model to include dementia using published data from primary care databases, health surveys, and trials of dementia to describe dementia incidence, diagnosis, and disease progression. We estimate the impact of dementia on lifetime costs and quality-adjusted life years (QALYs) gained of the National Health Service diabetes prevention program (NHS DPP) from an NHS/personal social services perspective with 3 scenarios: 1) no dementia, 2) dementia only, and 3) reduced dementia risk. Subgroup, parameter, and probabilistic sensitivity analyses were conducted. RESULTS: The lifetime cost savings of the NHS DPP per patient were £145 in the no-dementia scenario, £121 in the dementia-only scenario, and £167 in the reduced dementia risk scenario. The QALY gains increased by 0.0006 in dementia only and 0.0134 in reduced dementia risk. Dementia did not alter the recommendation that the NHS/DPP is cost-effective. CONCLUSIONS: Including dementia into a model of lifestyle interventions was feasible but did not change policy recommendations or modify health economic outcomes. The impact on health economic outcomes was largest where a direct impact on dementia incidence was assumed, particularly in elderly populations.National Institute for Health Research (NIHR) School for Public Health Research (SPHR). Grant Reference Number PD- SPH-201

The past, present and future of health geography: An exchange with three long standing participants in the Geographies of Health and Wellbeing Research Group

© 2024 The Authors. This is an open access article distributed under the Creative Commons Attribution License, to view a copy of the license, see: https://creativecommons.org/licenses/by/4.0/This article traces the past, present and future of health geography through the career journeys of three notable academics, Sarah Curtis (SC), Julia Jones (JJ) and Graham Moon (GM). All three of these scholars have had entanglements with the Geographies of Health and Wellbeing Research Group (GHWRG) of the Royal Geographical Society (with the Institute of British Geographers) (RGS‐IBG) throughout their careers, enabling them to shape health geography into the contemporary sub‐discipline that we know today. GHWRG has, for the last 50 years, offered a lively and supportive network for all those interested in the geographies of health and health care, medical geography and all other areas of scholarship related to health and wellbeing that engage with geographical concerns.Peer reviewe