Publications by authors named "Julie Watson"

70 Publications

Barriers and enablers of implementation of alcohol guidelines with pregnant women: a cross-sectional survey among UK midwives.

BMC Pregnancy Childbirth 2021 Feb 15;21(1):134. Epub 2021 Feb 15.

Nursing Studies, School of Health in Social Science, University of Edinburgh, Teviot Place, Edinburgh, EH8 9AG, UK.

Background: In 2016, the UK Chief Medical Officers revised their guidance on alcohol and advised women to abstain from alcohol if pregnant or planning pregnancy. Midwives have a key role in advising women about alcohol during pregnancy. The aim of this study was to investigate UK midwives' practices regarding the 2016 Chief Medical Officers Alcohol Guidelines for pregnancy, and factors influencing their implementation during antenatal appointments.

Methods: Online cross-sectional survey of a convenience sample of UK midwives recruited through professional networks and social media. Data were gathered using an anonymous online questionnaire addressing knowledge of the 2016 Alcohol Guidelines for pregnancy; practice behaviours regarding alcohol assessment and advice; and questions based on the Theoretical Domains Framework (TDF) to evaluate implementation of advising abstinence at antenatal booking and subsequent antenatal appointments.

Results: Of 842 questionnaire respondents, 58% were aware of the 2016 Alcohol Guidelines of whom 91% (438) cited abstinence was recommended, although 19% (93) cited recommendations from previous guidelines. Nonetheless, 97% of 842 midwives always or usually advised women to abstain from alcohol at the booking appointment, and 38% at subsequent antenatal appointments. Mean TDF domain scores (range 1-7) for advising abstinence at subsequent appointments were highest (indicative of barriers) for social influences (3.65 sd 0.84), beliefs about consequences (3.16 sd 1.13) and beliefs about capabilities (3.03 sd 073); and lowest (indicative of facilitators) for knowledge (1.35 sd 0.73) and professional role and identity (1.46 sd 0.77). Logistic regression analysis indicated that the TDF domains: beliefs about capabilities (OR = 0.71, 95% CI: 0.57, 0.88), emotion (OR = 0.78; 95%CI: 0.67, 0.90), and professional role and identity (OR = 0.69, 95%CI 0.51, 0.95) were strong predictors of midwives advising all women to abstain from alcohol at appointments other than at booking.

Conclusions: Our results suggest that skill development and reinforcement of support from colleagues and the wider maternity system could support midwives' implementation of alcohol advice at each antenatal appointment, not just at booking could lead to improved outcomes for women and infants. Implementation of alcohol care pathways in maternity settings are beneficial from a lifecourse perspective for women, children, families, and the wider community.
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http://dx.doi.org/10.1186/s12884-021-03583-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7885406PMC
February 2021

Profiling of H3K27Ac Reveals the Influence of Asthma on the Epigenome of the Airway Epithelium.

Front Genet 2020 10;11:585746. Epub 2020 Dec 10.

Peter Gorer Department of Immunobiology, King's College London, London, United Kingdom.

Background: Asthma is a chronic airway disease driven by complex genetic-environmental interactions. The role of epigenetic modifications in bronchial epithelial cells (BECs) in asthma is poorly understood.

Methods: We piloted genome-wide profiling of the enhancer-associated histone modification H3K27ac in BECs from people with asthma ( = 4) and healthy controls ( = 3).

Results: We identified = 4,321 (FDR < 0.05) regions exhibiting differential H3K27ac enrichment between asthma and health, clustering at genes associated predominately with epithelial processes (EMT). We identified initial evidence of asthma-associated Super-Enhancers encompassing genes encoding transcription factors () and enzymes regulating lipid metabolism (). We integrated published datasets to identify epithelium-specific transcription factors associated with H3K27ac in asthma () and identify initial relationships between asthma-associated changes in H3K27ac and transcriptional profiles. Finally, we investigated the potential of CRISPR-based approaches to functionally evaluate H3K27ac-asthma landscape by identifying guide-RNAs capable of targeting acetylation to asthma DERs and inducing gene expression ().

Conclusion: Our small pilot study validates genome-wide approaches for deciphering epigenetic mechanisms underlying asthma pathogenesis in the airways.
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http://dx.doi.org/10.3389/fgene.2020.585746DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7758344PMC
December 2020

Two Secreted Proteoglycans, Activators of Urothelial Cell-Cell Adhesion, Negatively Contribute to Bladder Cancer Initiation and Progression.

Cancers (Basel) 2020 Nov 13;12(11). Epub 2020 Nov 13.

UCL Institute of Ophthalmology, University College London, 11-43 Bath Street, London EC1V 9EL, UK.

Osteomodulin (OMD) and proline/arginine-rich end leucine repeat protein (PRELP) are secreted extracellular matrix proteins belonging to the small leucine-rich proteoglycans family. We found that OMD and PRELP were specifically expressed in umbrella cells in bladder epithelia, and their expression levels were dramatically downregulated in all bladder cancers from very early stages and various epithelial cancers. Our in vitro studies including gene expression profiling using bladder cancer cell lines revealed that OMD or PRELP application suppressed the cancer progression by inhibiting TGF-β and EGF pathways, which reversed epithelial-mesenchymal transition (EMT), activated cell-cell adhesion, and inhibited various oncogenic pathways. Furthermore, the overexpression of OMD in bladder cancer cells strongly inhibited the anchorage-independent growth and tumorigenicity in mouse xenograft studies. On the other hand, we found that in the bladder epithelia, the knockout mice of OMD and/or PRELP gene caused partial EMT and a loss of tight junctions of the umbrella cells and resulted in formation of a bladder carcinoma in situ-like structure by spontaneous breakdowns of the umbrella cell layer. Furthermore, the ontological analysis of the expression profiling of an OMD knockout mouse bladder demonstrated very high similarity with those obtained from human bladder cancers. Our data indicate that OMD and PRELP are endogenous inhibitors of cancer initiation and progression by controlling EMT. OMD and/or PRELP may have potential for the treatment of bladder cancer.
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http://dx.doi.org/10.3390/cancers12113362DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7697838PMC
November 2020

A qualitative assessment of psychosocial aspects that play a role in bladder management after spinal cord injury.

Spinal Cord 2020 Sep 8. Epub 2020 Sep 8.

Department of Classical Studies, Western University, London, ON, Canada.

Study Design: Prospective qualitative study using semi-structured, open-ended interviews.

Objectives: To better understand psychosocial aspects of bladder management after spinal cord injury (SCI).

Setting: People with SCI, recruited through three tertiary care centres in North America.

Methods: Thirty-four community-dwelling individuals with SCI were selected using purposive sampling to ensure men and women with both tetraplegia and paraplegia were represented. The interviews were audio recorded and transcribed. NVivo software was used to code psychosocial domains, medical complications, and methods of bladder management. A qualitative interpretive approach was used, and four participants participated in a debrief session to review the study findings.

Results: The median age was 49 (IQR 40-62) years and 61% (21/34) were male. Most had complete injuries (AIS A, 47%, 16/34), and most had a cervical lesion (56%, 19/34). There was a large range of time living with a SCI (median 20 years, IQR 9-31), and most participants managed their bladder with intermittent catheterisation (67% 23/34). The five most common psychosocial domains were anxiety (often in the context of urinary infections, incontinence, or not being able to catheterise), loss of control (due to irregular bladder behaviour), and embarrassment (from incontinence occurring in public); the domains of confidence and independence/planning included both positive and negative examples of bladder management experiences.

Conclusions: This study demonstrated consistent psychosocial topics related to bladder management in people living with SCI. This information will help counsel people regarding bladder management and identify areas for education and optimisation of bladder function from a psychosocial perspective.
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http://dx.doi.org/10.1038/s41393-020-00538-9DOI Listing
September 2020

Distal lung epithelial progenitor cell function declines with age.

Sci Rep 2020 06 26;10(1):10490. Epub 2020 Jun 26.

Research and Early Development, Respiratory & Immunology, BioPharmaceuticals R&D, AstraZeneca, Cambridge, UK.

Tissue stem cell exhaustion is a key hallmark of aging, and in this study, we characterised its manifestation in the distal lung. We compared the lungs of 3- and 22-month old mice. We examined the gross morphological changes in these lungs, the density and function of epithelial progenitor populations and the epithelial gene expression profile. Bronchioles became smaller in their cross-sectional area and diameter. Using long-term EdU incorporation analysis and immunohistochemistry, we found that bronchiolar cell density remained stable with aging, but inferred rates of bronchiolar club progenitor cell self-renewal and differentiation were reduced, indicative of an overall slowdown in cellular turnover. Alveolar Type II progenitor cell density and self-renewal were maintained per unit tissue area with aging, but rates of inferred differentiation into Type I cells, and indeed overall density of Type I cells was reduced. Microarray analysis revealed age-related changes in multiple genes, including some with roles in proliferation and differentiation, and in IGF and TGFβ signalling pathways. By characterising how lung stem cell dynamics change with aging, this study will elucidate how they contribute to age-related loss of pulmonary function, and pathogenesis of common age-related pulmonary diseases.
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http://dx.doi.org/10.1038/s41598-020-66966-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7319976PMC
June 2020

Child handwashing in an internally displaced persons camp in Northern Iraq: A qualitative multi-method exploration of motivational drivers and other handwashing determinants.

PLoS One 2020 3;15(2):e0228482. Epub 2020 Feb 3.

Department for Disease Control, London School of Hygiene and Tropical Medicine, London, England, United Kingdom.

Background: Children in humanitarian situations are particularly vulnerable to diseases such as diarrhoea. Handwashing with soap can greatly reduce transmission but handwashing rates are often low and traditional interventions ineffective. To aid future intervention design, this study aims to understand the determinants of child handwashing and the key motivational drivers of children's behaviour within a specific humanitarian setting.

Methods: In an internally displaced persons camp in Northern Iraq we conducted a series of 36 friendship-paired interviews with children aged 7-12 years, six semi-structured caregiver interviews, and three semi-structured hygiene promoter interviews. Perceived determinants of child handwashing were explored qualitatively, and motivational drivers were explored quantitatively with children in a rating exercise. Qualitative data were analysed thematically, using an inductive approach, and logistic regression analyses of motive rating data were performed to determine the predicted probabilities of motives being rated as important.

Results: Access to soap and water was perceived to be high across all participant groups. Children, caregivers and hygiene promoters all perceive the determinants of child handwashing to be associated with familial role, environmental factors pertaining to location and quality of handwashing materials and facilities, and level of exposure to hygiene promotion, and children also attribute their handwashing to social norms. We find that children in this context are motived most by play and nurture.

Conclusions: Provision of soap and water alone is not sufficient to encourage children to practice handwashing with soap in a humanitarian context. Our findings suggest that equal consideration should be given to the quality and location of handwashing materials and facilities and social norms could be leveraged to promote and enhance child handwashing. Motive-based interventions targeting play or nurture may be a promising approach and are likely most effective when used in conjunction, along with other motivational drivers such as affiliation and love.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0228482PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6996827PMC
May 2020

Interventions to improve water supply and quality, sanitation and handwashing facilities in healthcare facilities, and their effect on healthcare-associated infections in low-income and middle-income countries: a systematic review and supplementary scoping review.

BMJ Glob Health 2019 8;4(4):e001632. Epub 2019 Jul 8.

Disease Control, London School of Hygiene and Tropical Medicine, Faculty of Infectious and Tropical Diseases, London, UK.

Introduction: Healthcare-associated infections (HCAIs) are the most frequent adverse event compromising patient safety globally. Patients in healthcare facilities (HCFs) in low-income and middle-income countries (LMICs) are most at risk. Although water, sanitation and hygiene (WASH) interventions are likely important for the prevention of HCAIs, there have been no systematic reviews to date.

Methods: As per our prepublished protocol, we systematically searched academic databases, trial registers, WHO databases, grey literature resources and conference abstracts to identify studies assessing the impact of HCF WASH services and practices on HCAIs in LMICs. In parallel, we undertook a supplementary scoping review including less rigorous study designs to develop a conceptual framework for how WASH can impact HCAIs and to identify key literature gaps.

Results: Only three studies were included in the systematic review. All assessed hygiene interventions and included: a cluster-randomised controlled trial, a cohort study, and a matched case-control study. All reported a reduction in HCAIs, but all were considered at medium-high risk of bias. The additional 27 before-after studies included in our scoping review all focused on hygiene interventions, none assessed improvements to water quantity, quality or sanitation facilities. 26 of the studies reported a reduction in at least one HCAI. Our scoping review identified multiple mechanisms by which WASH can influence HCAI and highlighted a number of important research gaps.

Conclusions: Although there is a dearth of evidence for the effect of WASH in HCFs, the studies of hygiene interventions were consistently protective against HCAIs in LMICs. Additional and higher quality research is urgently needed to fill this gap to understand how WASH services in HCFs can support broader efforts to reduce HCAIs in LMICs.

Prospero Registration Number: CRD42017080943.
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http://dx.doi.org/10.1136/bmjgh-2019-001632DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6626521PMC
July 2019

A systematic review and meta-analysis in the effectiveness of mobile phone interventions used to improve adherence to antiretroviral therapy in HIV infection.

BMC Public Health 2019 Jul 9;19(1):915. Epub 2019 Jul 9.

London School of Hygiene and Tropical Medicine (LSHTM), London, UK.

Background: Antiretroviral therapy is effective in preventing the progression of HIV to AIDS, but adherence to HIV medication is lower than ideal. A previous Cochrane review concluded that SMS interventions increased adherence to HIV medication, but more recent trials have reported mixed results. Our review aims to provide an up-to-date synthesis of the effects of interventions delivered by mobile phone on adherence.

Methods: We searched Cochrane, Medline, CINAHL, EMBASE and Global Health for randomised control trials (RCTs) of interventions delivered by mobile phones, designed to increase adherence to antiretroviral medication. Risk of bias was assessed using the Cochrane risk of bias tool. We calculated relative risk ratios (RR) or standardised mean difference (SMD) with 95% confidence interval (CI). Trials were analysed depending on delivery mechanism and intervention characteristics. We conducted meta-analysis for primary objective outcome measures.

Results: We identified 19 trials. No trials were at low risk of bias. Interventions were delivered as follows; nine via text message, five via mobile phone call, one via mobile phone imagery and four via mixed interventions. There was no effect when interventions delivered by text message were pooled in the RR1.25 (CI 0.97 to 1.61) P = 0.08. The SMD 0.42 (0.03 to 0.81) p = 0.04 showed a moderate effect to improve adherence. There was mixed evidence of the effect of text messages delivered daily, weekly, at scheduled or triggered times, however, messages with link to support, interactivity and three or more behavior change techniques (BCTs) all improved adherence. Of the five trials delivered by mobile phone call, one reported a reduction in HIV viral load. One trial using mobile phone imagery reported a reduction in HIV viral load. Three trials that delivered interventions by text message and mobile phone counselling reported improved biological outcomes.

Conclusion: Specific interventions, of proven effectiveness should be considered for implementation, rather than mobile phone-based interventions in general. Interventions targeting a wider range of barriers to adherence may be more effective than existing interventions. The effects and cost-effectiveness of such interventions should be evaluated in a randomised controlled trial alongside long term objective and clinically important outcomes.
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http://dx.doi.org/10.1186/s12889-019-6899-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6617638PMC
July 2019

What matters to people with memory problems, healthy volunteers and health and social care professionals in the context of developing treatment to prevent Alzheimer's dementia? A qualitative study.

Health Expect 2019 06 27;22(3):504-517. Epub 2019 Feb 27.

Edinburgh Centre for Research on the Experience of Dementia (ECRED), School of Health in Social Science, University of Edinburgh, Edinburgh, UK.

Background: Alzheimer's disease (AD) is recognized as one of the greatest global public health challenges. There is increasing consensus that optimal disease modification using pharmaceuticals may best be achieved earlier in the disease continuum before symptoms occur. However, more needs to be understood about what outcomes are meaningful to potential participants in clinical trials within this preventative paradigm and how people make trade-offs between risks and benefits. The Electronic Person-Specific Outcome Measure (ePSOM) programme is developing an app to capture person-specific outcomes and preferences in clinical trials.

Objective: As one phase in the ePSOM programme, this study explored what matters when developing new treatments to prevent AD and how trade-offs are made between risks and benefits, from three perspectives.

Design: Focus groups were conducted with people living with memory problems (n = 21) and healthy volunteers (n = 10), and telephone interviews with health and social care professionals (n = 10). Differences and overlap between the three groups were explored.

Results: Outcomes that matter lie in five key domains in relation to what matters in everyday life: Everyday Functioning; Relationships and Social Connections; Enjoying Life; Sense of Identity; and Alleviating  Symptoms. Insights were gained into the significance of reducing the risk of developing dementia with drugs and the processes of weighing up risks versus benefits.

Discussion And Conclusions: The key domains identified are being used to inform the next stage of the ePSOM programme which is to develop a survey to be distributed nationally in the UK to explore these issues further.
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http://dx.doi.org/10.1111/hex.12876DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6543163PMC
June 2019

Participant outcomes and preferences in Alzheimer's disease clinical trials: The electronic Person-Specific Outcome Measure (ePSOM) development program.

Alzheimers Dement (N Y) 2018 12;4:694-702. Epub 2018 Dec 12.

Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh, UK.

Introduction: Current pharmacological interventions for Alzheimer's dementia delay symptom progression for about a year. Although the outcomes in earlier disease states may include changes in biomarkers, the clinical effectiveness of any intervention can ultimately only be assessed by a patient's self-reported well-being. A better understanding of earlier manifestations of Alzheimer's disease and the drive for relevant outcome measures, allied to technological advances in artificial intelligence, have mediated the electronic Person-Specific Outcome Measure (ePSOM) development program.

Methods: There are 4 sequential stages in the ePSOM development program-(1) literature review, (2) focus group study, (3) national survey, and (4) development of an app for capturing person-specific outcomes. Here, we report the overall approach to the program incorporating our literature review on patient-reported outcome measures and patient preferences in the Alzheimer's disease population.

Results: Alzheimer's disease trials do not use any patient-reported outcome measures. Quality of life measures are often used as proxies for this, but they do not capture individual needs. Therefore, trials currently fail to reflect the participant's aspirations for effect but rather default to clinicostatistical measure of cognition and function. There is no implementation of patient preferences despite evidence that understanding preferences may influence adherence to treatment.

Discussion: It is important to consider preferences for an intervention and use PROMs for the measure of effectiveness given that both risk and benefit are judged by the recipient of the treatment. The ePSOM development program will deliver the methodology for incorporating meaningful outcomes in clinical trials to expand upon current biological and clinical measurements of effectiveness.
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http://dx.doi.org/10.1016/j.trci.2018.10.013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6296160PMC
December 2018

A new highly sensitive enzyme-linked immunosorbent assay for the detection of Plasmodium falciparum histidine-rich protein 2 in whole blood.

Malar J 2018 Nov 1;17(1):403. Epub 2018 Nov 1.

Diagnostics Program, PATH, Seattle, WA, USA.

Background: The detection of submicroscopic infections in low prevalence settings has become an increasingly important challenge for malaria elimination strategies. The current field rapid diagnostic tests (RDTs) for Plasmodium falciparum malaria are inadequate to detect low-density infections. Therefore, there is a need to develop more sensitive field diagnostic tools. In parallel, a highly sensitive laboratory reference assay will be essential to evaluate new diagnostic tools. Recently, the highly sensitive Alere™ Malaria Ag P.f ELISA (HS ELISA) was developed to detect P. falciparum histidine-rich protein 2 (HRP2) in clinical whole blood specimens. In this study, the analytical and clinical performance of the HS ELISA was determined using recombinant P. falciparum HRP2, P. falciparum native culture parasites, and archived highly pedigreed clinical whole blood specimens from Karen village, Myanmar and Nagongera, Uganda.

Results: The HS ELISA has an analytical sensitivity of less than 25 pg/mL and shows strong specificity for P. falciparum HRP2 when tested against P. falciparum native culture strains with pfhrp2 and pfhrp3 gene deletions. Additionally, the Z'-factor statistic of 0.862 indicates the HS ELISA as an excellent, reproducible assay, and the coefficients of variation for inter- and intra-plate testing, 11.76% and 2.51%, were acceptable. Against clinical whole blood specimens with concordant microscopic and PCR results, the HS ELISA showed 100% (95% CI 96.4-100) diagnostic sensitivity and 97.9% (95% CI 94.8-99.4) diagnostic specificity. For P. falciparum positive specimens with HRP2 concentrations below 400 pg/mL, the sensitivity and specificity were 100% (95% CI 88.4-100) and 88.9% (95% CI 70.8-97.6), respectively. The overall sensitivity and specificity for all 352 samples were 100% (CI 95% 96-100%) and 97.3% (CI 95% 94-99%).

Conclusions: The HS ELISA is a robust and reproducible assay. The findings suggest that the HS ELISA may be a useful tool as an affordable reference assay for new ultra-sensitive HRP2-based RDTs.
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http://dx.doi.org/10.1186/s12936-018-2545-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6211401PMC
November 2018

Child's play: Harnessing play and curiosity motives to improve child handwashing in a humanitarian setting.

Int J Hyg Environ Health 2019 03 13;222(2):177-182. Epub 2018 Sep 13.

Department for Disease Control, London School of Hygiene and Tropical Medicine, Keppel St, Bloomsbury, London, WC1E 7HT, UK.

In humanitarian emergency settings there is need for low cost and rapidly deployable interventions to protect vulnerable children, in- and out-of-school, from diarrhoeal diseases. Handwashing with soap can greatly reduce diarrhoea but interventions specifically targeting children's handwashing behaviour in humanitarian settings have not been tested. Traditional children's handwashing promotion interventions have been school-focused, resource-intensive and reliant on health-based messaging. However, recent research from non-humanitarian settings and targeting adults suggests that theory-based behaviour change interventions targeting specific motives may be more effective than traditional handwashing interventions. In this proof-of-concept study we test, for the first time, the distribution of a modified soap bar, designed to appeal to the motives of play and curiosity, in a household-level, rapidly deployable, handwashing promotion intervention for older children in a humanitarian setting - an internally displaced persons camp in Iraqi Kurdistan. Out of five total blocks within the camp, one was assigned to intervention and one to control. 40 households from each assigned block were then randomly chosen for inclusion in the study and the practice of handwashing with soap at key times was measured at baseline and four weeks after intervention delivery. Children in intervention households received transparent soaps with embedded toys, delivered within a short, fun, and interactive household session with minimal, non-health-based, messaging. The control group received plain soap delivered in a short standard, health-based, hygiene promotion session. At the 4-week follow-up, children in the intervention group were 4 times more likely to wash their hands with soap after key handwashing occasions than expected in the counterfactual (if there had been no intervention) based on the comparison to children in the control group (adjusted RR = 3.94, 95% CI 1.59-9.79). We show that distributing soaps with toys embedded inside, in a rapidly deployable intervention, can improve child handwashing behaviour in a humanitarian emergency context. Further studies are needed to determine the longer-term behavioural and health impact of such an intervention when delivered at a greater scale in a humanitarian context.
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http://dx.doi.org/10.1016/j.ijheh.2018.09.002DOI Listing
March 2019

BCL11A interacts with SOX2 to control the expression of epigenetic regulators in lung squamous carcinoma.

Nat Commun 2018 08 20;9(1):3327. Epub 2018 Aug 20.

Department of Pharmacology, University of Cambridge, Cambridge, CB2 1PD, UK.

Patients diagnosed with lung squamous cell carcinoma (LUSC) have limited targeted therapies. We report here the identification and characterisation of BCL11A, as a LUSC oncogene. Analysis of cancer genomics datasets revealed BCL11A to be upregulated in LUSC but not in lung adenocarcinoma (LUAD). Experimentally we demonstrate that non-physiological levels of BCL11A in vitro and in vivo promote squamous-like phenotypes, while its knockdown abolishes xenograft tumour formation. At the molecular level we found that BCL11A is transcriptionally regulated by SOX2 and is required for its oncogenic functions. Furthermore, we show that BCL11A and SOX2 regulate the expression of several transcription factors, including SETD8. We demonstrate that shRNA-mediated or pharmacological inhibition of SETD8 selectively inhibits LUSC growth. Collectively, our study indicates that BCL11A is integral to LUSC pathology and highlights the disruption of the BCL11A-SOX2 transcriptional programme as a novel candidate for drug development.
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http://dx.doi.org/10.1038/s41467-018-05790-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6102279PMC
August 2018

A Seat Around the Table: Participatory Data Analysis With People Living With Dementia.

Qual Health Res 2018 07 16;28(9):1421-1433. Epub 2018 May 16.

3 Mental Health Foundation, London, United Kingdom.

The involvement of "people with experience" in research has developed considerably in the last decade. However, involvement as co-analysts at the point of data analysis and synthesis has received very little attention-in particular, there is very little work that involves people living with dementia as co-analysts. In this qualitative secondary data analysis project, we (a) analyzed data through two theoretical lenses: Douglas's cultural theory of risk and Tronto's Ethic of Care, and (b) analyzed data in workshops with people living with dementia. The design involved cycles of presenting, interpreting, representing and reinterpreting the data, and findings between multiple stakeholders. We explore ways of involving people with experience as co-analysts and explore the role of reflexivity, multiple voicing, literary styling, and performance in participatory data analysis.
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http://dx.doi.org/10.1177/1049732318774768DOI Listing
July 2018

Fank1 and Jazf1 promote multiciliated cell differentiation in the mouse airway epithelium.

Biol Open 2018 Apr 16;7(4). Epub 2018 Apr 16.

Wellcome Trust/CRUK Gurdon Institute, Wellcome Trust/MRC Stem Cell Institute, Department of Pathology, University of Cambridge, Cambridge, CB2 1QN, UK

The airways are lined by secretory and multiciliated cells which function together to remove particles and debris from the respiratory tract. The transcriptome of multiciliated cells has been extensively studied, but the function of many of the genes identified is unknown. We have established an assay to test the ability of over-expressed transcripts to promote multiciliated cell differentiation in mouse embryonic tracheal explants. Overexpression data indicated that () and () promoted multiciliated cell differentiation alone, and cooperatively with the canonical multiciliated cell transcription factor Foxj1. Moreover, knock-down of or in adult mouse airway epithelial cultures demonstrated that these factors are both required for ciliated cell differentiation This analysis identifies and as novel regulators of multiciliated cell differentiation. Moreover, we show that they are likely to function downstream of IL6 signalling and upstream of Foxj1 activity in the process of ciliated cell differentiation. In addition, our explant assay provides a convenient method for preliminary investigation of over-expression phenotypes in the developing mouse airways.This article has an associated First Person interview with the first author of the paper.
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http://dx.doi.org/10.1242/bio.033944DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5936064PMC
April 2018

Visceral Leishmaniasis in Traveler to Guyana Caused by Leishmania siamensis, London, UK.

Emerg Infect Dis 2018 01;24(1):155-156

The parasite Leishmania siamensis is a zoonotic agent of leishmaniasis; infection in animals has been documented in Europe and the United States. Reported authochthonous human infections have been limited to Thailand. We report a case of human visceral Leishmania siamensis infection acquired in Guyana, suggesting colonization in South America.
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http://dx.doi.org/10.3201/eid2401.161428DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5749450PMC
January 2018

The changing aetiology of eosinophilia in migrants and returning travellers in the Hospital for Tropical Diseases, London 2002-2015: An observational study.

J Infect 2017 10 24;75(4):301-308. Epub 2017 Aug 24.

Infectious Diseases and Tropical Medicine, Hospital for Tropical Diseases, University College London Hospitals NHS Trust, UK. Electronic address:

Introduction: Determining the cause of eosinophilia in patients returning from the tropics continues to present a diagnostic challenge. The history, symptoms and degree of eosinophilia are often poor predictors of eventual diagnosis, but helminths are an important cause. The current British Infection Association recommendations use travel history to guide investigation of eosinophilia. However the global burden of helminth disease and travel patterns have changed over the last 3 decades and guidelines based on previous epidemiology need to be reviewed in the light of current data.

Methods: Consecutive patients presenting with, or referred for, investigation of eosinophilia were identified prospectively. Case notes, laboratory results and electronic records were reviewed for demographic and clinical data. Patients with an eosinophil count ≥0.50 × 10/L were included, and grouped based on lifetime history of travel to: West Africa, elsewhere in Africa, and the rest of the world. Results were compared to published data from 1997 to 2002 collected at the same centre.

Results: Of 410 patients who met the inclusion criteria, 407 had a documented travel history. Average yearly referrals for eosinophilia fell from 58 per year between 1997 and 2002, to 33 per year (2002-2015). The proportion of eosinophilia cases diagnosed with a parasitic cause fell from 64% to 50%, and yields for all parasitological investigations fell, the largest reduction in stool microscopy (20% yield to 9%) and day bloods for microfilariae (14% yield to 3%). Strongyloides stercoralis was the commonest diagnosis overall in our cohort, accounting for 50% of the total parasites diagnosed, and was present in 38% of patients from West Africa, 19% from rest of Africa, and 34% from rest of world; a relative increase compared to previous data. Schistosomiasis is slightly less common in those who had travelled to West Africa than the rest of Africa, and overall point prevalence has fallen from 33% (1997-2002) to 17% (2002-2015). Travellers were significantly less likely than patients who had immigrated to the UK to be diagnosed with any parasite (OR 0.54 95% CI 0.378-0.778 p = 0.0009).

Discussion: A parasitic cause will still be found in half of people returning from the tropics with an eosinophilia, but we observed a fall in the overall prevalence of parasitic diagnoses when compared with the earlier data. This may, in part, be explained by the impact of control programmes on the prevalence of parasites globally, especially filarial disease. S. stercoralis now represents the majority of parasites diagnosed in our cohort from all continents. We identified significantly higher rates of strongyloidiasis in immigrants than returning travellers. Despite the falling yields of stool microscopy and filarial serology the current guidelines based on travel history remain relevant with adequate yield.
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http://dx.doi.org/10.1016/j.jinf.2017.08.007DOI Listing
October 2017

Does targeting children with hygiene promotion messages work? The effect of handwashing promotion targeted at children, on diarrhoea, soil-transmitted helminth infections and behaviour change, in low- and middle-income countries.

Trop Med Int Health 2017 05 31;22(5):526-538. Epub 2017 Mar 31.

Department for Disease Control, London School of Hygiene and Tropical Medicine, London, UK.

Objectives: To synthesise evidence on the effect of handwashing promotion interventions targeting children, on diarrhoea, soil-transmitted helminth infection and handwashing behaviour, in low- and middle-income country settings.

Methods: A systematic review of the literature was performed by searching eight databases, and reference lists were hand-searched for additional articles. Studies were reviewed for inclusion according to pre-defined inclusion criteria and the quality of all studies was assessed.

Results: Eight studies were included in this review: seven cluster-randomised controlled trials and one cluster non-randomised controlled trial. All eight studies targeted children aged 5-12 attending primary school but were heterogeneous for both the type of intervention and the reported outcomes so results were synthesised qualitatively. None of the studies were of high quality and the large majority were at high risk of bias. The reported effect of child-targeted handwashing interventions on our outcomes of interest varied between studies. Of the different interventions reported, no one approach to promoting handwashing among children appeared most effective.

Conclusion: Our review found very few studies that evaluated handwashing interventions targeting children and all had various methodological limitations. It is plausible that interventions which succeed in changing children's handwashing practices will lead to significant health impacts given that much of the attributable disease burden is concentrated in that age group. The current paucity of evidence in this area, however, does not permit any recommendations to be made as to the most effective route to increasing handwashing with soap practice among children in LMIC.
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http://dx.doi.org/10.1111/tmi.12861DOI Listing
May 2017

Anti-myeloperoxidase antibodies attenuate the monocyte response to LPS and shape macrophage development.

JCI Insight 2017 01 26;2(2):e87379. Epub 2017 Jan 26.

Division of Transplant Immunology and Mucosal Biology, MRC Centre for Transplantation, King's College London, Guy's Hospital, Great Maze Pond, London, United Kingdom.

Anti-neutrophil cytoplasmic antibody (ANCA) vasculitis is characterized by the presence of autoantibodies to myeloperoxidase and proteinase-3, which bind monocytes in addition to neutrophils. While a pathological effect on neutrophils is acknowledged, the impact of ANCA on monocyte function is less well understood. Using IgG from patients we investigated the effect of these autoantibodies on monocytes and found that anti-myeloperoxidase antibodies (MPO-ANCA) reduced both IL-10 and IL-6 secretion in response to LPS. This reduction in IL-10 and IL-6 depended on Fc receptors and enzymatic myeloperoxidase and was accompanied by a significant reduction in TLR-driven signaling pathways. Aligning with changes in TLR signals, oxidized phospholipids, which function as TLR4 antagonists, were increased in monocytes in the presence of MPO-ANCA. We further observed that MPO-ANCA increased monocyte survival and differentiation to macrophages by stimulating CSF-1 production. However, this was independent of myeloperoxidase enzymatic activity and TLR signaling. Macrophages differentiated in the presence of MPO-ANCA secreted more TGF-β and further promoted the development of IL-10- and TGF-β-secreting CD4 T cells. Thus, MPO-ANCA may promote inflammation by reducing the secretion of antiinflammatory IL-10 from monocytes, and MPO-ANCA can alter the development of macrophages and T cells to potentially promote fibrosis.
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http://dx.doi.org/10.1172/jci.insight.87379DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5256146PMC
January 2017

Nursing home residents prefer fewer interventions and the nursing home instead of hospital for place of death.

Authors:
Julie Watson

Evid Based Nurs 2017 01 1;20(1):24. Epub 2016 Dec 1.

Edinburgh Centre for Research on the Experience of Dementia, University of Edinburgh, Edinburgh, UK.

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http://dx.doi.org/10.1136/eb-2016-102522DOI Listing
January 2017

Developing the Senses Framework to support relationship-centred care for people with advanced dementia until the end of life in care homes.

Authors:
Julie Watson

Dementia (London) 2019 Feb 6;18(2):545-566. Epub 2016 Dec 6.

School of Health in Social Sciences (Nursing Studies), Edinburgh Centre for Research on the Experience of Dementia, University of Edinburgh, Edinburgh, UK.

People with advanced dementia living in care homes can experience social death before their physical death. Social death occurs when a person is no longer recognised as being an active agent within their relationships. A shift is required in how we perceive people with advanced dementia so that the ways they continue to be active in their relationships are noticed. Paying attention to embodied and interembodied selfhood broadens the scope and opportunities for relationships with people with advanced dementia, acting as a counter to social death. This has the potential to improve the quality of care, including end of life care, of people with advanced dementia in care homes. This study examined the role of embodied and interembodied selfhood within care-giving/care-receiving relationships in a specialist dementia care home. Empirical findings and their implications for the development of relationship-centred care and the Senses Framework in care homes are discussed.
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http://dx.doi.org/10.1177/1471301216682880DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6376605PMC
February 2019

Guidance Regarding Sample Collection and Refinement of Fecal Flotation Exam for the Isolation of Aspiculuris tetraptera.

J Am Assoc Lab Anim Sci 2016 ;55(5):541-7

Research Animal Resources, Department of Molecular and Comparative Pathobiology, Johns Hopkins School of Medicine, Baltimore, Maryland, USA.

Aspiculuris tetraptera continues to be a problem in rodent vivaria, in part due to difficulties in parasite detection. Although PCR testing is highly sensitive, it is expensive and does not always provide immediate results. Consequently, many institutions rely on passive fecal flotation as a quick inhouse exam for diagnosing A. tetraptera infections. To increase the sensitivity of this test, we examined multiple parameters to determine the optimal test protocol. A 30-min soaking period prior to fecal flotation for 15 min allowed fecal pellets to soften and facilitated efficient egg isolation. We also evaluated the effect of time of day, sample size, age, sex, and housing status on egg isolation. No evidence of cyclical egg shedding was found, and although larger fecal sample sizes did not result in more eggs isolated, their use reduced the incidence of false-negative exams. The most eggs were isolated from 8- and 12-wk-old mice, and as mice aged, the number of eggs isolated declined. Overall, neither sex nor housing status influenced the number of eggs isolated. Finally, examination of multiple diagnostic tests (fecal flotation exam, direct examination of cecal and colonic contents, and fecal PCR) revealed that no single test was definitive, thus indicating that multiple tests might be required to successfully screen mice with low pinworm burdens. These findings provide guidance regarding sample selection, collection, and processing to efficiently detect A. tetraptera.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5029824PMC
August 2017

Fixing the broken image of care homes, could a 'care home innovation centre' be the answer?

Age Ageing 2017 03;46(2):175-178

Usher Institute of Population Health Sciences and Informatics, Primary Palliative Care Research Group, Medical School, Edinburgh EH8 9AG, UK.

The UK has many excellent care homes that provide high-quality care for their residents; however, across the care home sector, there is a significant need for improvement. Even though the majority of care homes receive a rating of 'good' from regulators, still significant numbers are identified as requiring 'improvement' or are 'inadequate'. Such findings resonate with the public perceptions of long-term care as a negative choice, to be avoided wherever possible-as well as impacting on the career choices of health and social care students. Projections of current demographics highlight that, within 10 years, the part of our population that will be growing the fastest will be those people older than 80 years old with the suggestion that spending on long-term care provision needs to rise from 0.6% of our Gross Domestic Product in 2002 to 0.96% by 2031. Teaching/research-based care homes have been developed in the USA, Canada, Norway, the Netherlands and Australia in response to scandals about care, and the shortage of trained geriatric healthcare staff. There is increasing evidence that such facilities help to reduce inappropriate hospital admissions, increase staff competency and bring increased enthusiasm about working in care homes and improve the quality of care. Is this something that the UK should think of developing? This commentary details the core goals of a Care Home Innovation Centre for training and research as a radical vision to change the culture and image of care homes, and help address this huge public health issue we face.
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http://dx.doi.org/10.1093/ageing/afw154DOI Listing
March 2017

Responsive versus scheduled feeding for preterm infants.

Cochrane Database Syst Rev 2016 Aug 31(8):CD005255. Epub 2016 Aug 31.

Sheffield Hallam University, Sheffield, UK.

Background: Feeding preterm infants in response to their hunger and satiation cues (responsive, cue-based, or infant-led feeding) rather than at scheduled intervals might enhance infants' and parents' experience and satisfaction, help in the establishment of independent oral feeding, increase nutrient intake and growth rates, and allow earlier hospital discharge.

Objectives: To assess the effect of a policy of feeding preterm infants on a responsive basis versus feeding prescribed volumes at scheduled intervals on growth rates, levels of parent satisfaction, and time to hospital discharge.

Search Methods: We used the standard search strategy of the Cochrane Neonatal Review group to search the Cochrane Central Register of Controlled Trials (CENTRAL 2016, Issue 1), MEDLINE via PubMed (1966 to 17 February 2016), Embase (1980 to 17 February 2016), and CINAHL (1982 to 17 February 2016). We also searched clinical trials' databases, conference proceedings, and the reference lists of retrieved articles for randomised controlled trials and quasi-randomised trials.

Selection Criteria: Randomised controlled trials (RCTs) or quasi-RCTs that compared a policy of feeding preterm infants on a responsive basis versus feeding at scheduled intervals.

Data Collection And Analysis: Two review authors assessed trial eligibility and risk of bias and undertook data extraction independently. We analysed the treatment effects in the individual trials and reported the risk ratio and risk difference for dichotomous data and mean difference (MD) for continuous data, with respective 95% confidence intervals (CIs). We used a fixed-effect model in meta-analyses and explored the potential causes of heterogeneity in sensitivity analyses. We assessed the quality of evidence at the outcome level using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach.

Main Results: We found nine eligible RCTs including 593 infants in total. These trials compared responsive with scheduled interval regimens in preterm infants in the transition phase from intragastric tube to oral feeding. The trials were generally small and contained various methodological weaknesses including lack of blinding and incomplete assessment of all randomised participants. Meta-analyses, although limited by data quality and availability, suggest that responsive feeding results in slightly slower rates of weight gain (MD -1.36, 95% CI -2.44 to -0.29 g/kg/day), and provide some evidence that responsive feeding reduces the time taken for infants to transition from enteral tube to oral feeding (MD -5.53, 95% CI -6.80 to -4.25 days). GRADE assessments indicated low quality of evidence. The importance of this finding is uncertain as the trials did not find a strong or consistent effect on the duration of hospitalisation. None of the included trials reported any parent, caregiver, or staff views.

Authors' Conclusions: Overall, the data do not provide strong or consistent evidence that responsive feeding affects important outcomes for preterm infants or their families. Some (low quality) evidence exists that preterm infants fed in response to feeding and satiation cues achieve full oral feeding earlier than infants fed prescribed volumes at scheduled intervals. This finding should be interpreted cautiously because of methodological weaknesses in the included trials. A large RCT would be needed to confirm this finding and to determine if responsive feeding of preterm infants affects other important outcomes.
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http://dx.doi.org/10.1002/14651858.CD005255.pub5DOI Listing
August 2016

Ectoparasite Burden, Clinical Disease, and Immune Responses throughout Fur Mite (Myocoptes musculinus) Infestation in C57BL/6 and Rag1(-/-) Mice.

Comp Med 2016 ;66(3):197-207

Research Animal Resources, Johns Hopkins School of Medicine, Baltimore, Maryland, USA; Department of Molecular and Comparative Pathobiology, Johns Hopkins School of Medicine, Baltimore, Maryland, USA.

Immunocompetent weanling mice infested with Myocoptes musculinus harbor high mite loads, yet burdens decrease with age. The development of immunity to the parasite may explain this observation. In this study, we followed M. musculinus burdens in Rag1(-/-) mice and immunocompetent C57BL/6 controls from 4 to 36 wk of age and compared the clinical signs and body weights of noninfested and infested mice of both strains over time. In addition, histopathology of skin lesions and expression of cytokines and transcription factors associated with Th1- and Th2-type immune responses were assessed. Myocoptes burdens decreased and remained low in B6 mice over time, whereas Rag1(-/-) mice showed an initial decrease in burdens after 4 wk of age followed by an increase from 24 to 36 wk. In addition, Rag1(-/-) mice had higher burdens than B6 mice over time. Both strains of infested mice exhibited clinical signs of fur mite infestation-including alopecia, poor weight gain, mite-associated debris, and pruritus-and clinical signs positively correlated with the severity of the Myocoptes burden. Histopathology of skin from both strains of infested mice showed decreased lesion severity with age, likely a result of declining mite populations. Finally, compared with noninfested controls, infested B6 mice had increased expression of markers associated with the Th2-type immune response, which increased in magnitude with increasing age and duration of infestation. These results suggest that development of adaptive immunity plays a role in control of fur mite populations and that heavier infestations may result in more severe clinical signs and skin lesions.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4907528PMC
November 2017

Responsive versus scheduled feeding for preterm infants.

Cochrane Database Syst Rev 2015 Oct 13(10):CD005255. Epub 2015 Oct 13.

Sheffield Hallam University, Sheffield, UK.

Background: Feeding preterm infants in response to their hunger and satiation cues (responsive, cue-based, or infant-led feeding) rather than at scheduled intervals might enhance infants' and parents' experience and satisfaction, help in the establishment of independent oral feeding, increase nutrient intake and growth rates, and allow earlier hospital discharge.

Objectives: To assess the effect of feeding preterm infants on a responsive basis versus feeding prescribed volumes at scheduled intervals on growth, duration of hospital stay, and parental satisfaction.

Search Methods: We used the standard search strategy of the Cochrane Neonatal Review Group. This included searches of the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 9, 2015), MEDLINE (1966 to September 2015), EMBASE (1980 to September 2015), and CINAHL (1982 to September 2015), conference proceedings, previous reviews, and trial registries.

Selection Criteria: Randomised controlled trials (RCTs) or quasi-RCTs that compared a policy of feeding preterm infants on a responsive basis versus feeding at scheduled intervals.

Data Collection And Analysis: Two review authors assessed trial eligibility and risk of bias and undertook data extraction independently. We analysed the treatment effects in the individual trials and reported the risk ratio and risk difference for dichotomous data and mean difference (MD) for continuous data, with respective 95% confidence intervals (CIs). We used a fixed-effect model in meta-analyses and explored the potential causes of heterogeneity in sensitivity analyses.

Main Results: We found nine eligible RCTs including 593 infants in total. These trials compared responsive with scheduled interval regimens in preterm infants in the transition phase from intragastric tube to oral feeding. The trials were generally small and contained various methodological weaknesses including lack of blinding and incomplete assessment of all randomised participants. Meta-analyses, although limited by data quality and availability, suggest that responsive feeding results in slightly slower rates of weight gain (MD -1.4, 95% CI -2.4 to -0.3 g/kg/day), and provide some evidence that responsive feeding reduces the time taken for infants to transition from enteral tube to oral feeding (MD -5.5, 95% CI -6.8 to -4.2 days). The importance of this finding is uncertain as the trials did not find a strong or consistent effect on the duration of hospitalisation. None of the included trials reported any parent, caregiver, or staff views.

Authors' Conclusions: Overall, the data do not provide strong or consistent evidence that responsive feeding affects important outcomes for preterm infants or their families. Some evidence exists that preterm infants fed in response to feeding and satiation cues achieve full oral feeding earlier than infants fed prescribed volumes at scheduled intervals. However, this finding should be interpreted cautiously because of methodological weaknesses in the included trials. A large RCT would be needed to confirm this finding and to determine if responsive feeding of preterm infants affects other important outcomes.
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http://dx.doi.org/10.1002/14651858.CD005255.pub4DOI Listing
October 2015

Clonal Dynamics Reveal Two Distinct Populations of Basal Cells in Slow-Turnover Airway Epithelium.

Cell Rep 2015 Jul 25;12(1):90-101. Epub 2015 Jun 25.

Wellcome Trust/CRUK Gurdon Institute, University of Cambridge, Cambridge CB2 1QN, UK; Wellcome Trust-MRC Stem Cell Institute University of Cambridge, Cambridge CB2 3EG, UK; Department of Pathology, University of Cambridge, Cambridge CB2 3EG, UK. Electronic address:

Epithelial lineages have been studied at cellular resolution in multiple organs that turn over rapidly. However, many epithelia, including those of the lung, liver, pancreas, and prostate, turn over slowly and may be regulated differently. We investigated the mouse tracheal epithelial lineage at homeostasis by using long-term clonal analysis and mathematical modeling. This pseudostratified epithelium contains basal cells and secretory and multiciliated luminal cells. Our analysis revealed that basal cells are heterogeneous, comprising approximately equal numbers of multipotent stem cells and committed precursors, which persist in the basal layer for 11 days before differentiating to luminal fate. We confirmed the molecular and functional differences within the basal population by using single-cell qRT-PCR and further lineage labeling. Additionally, we show that self-renewal of short-lived secretory cells is a feature of homeostasis. We have thus revealed early luminal commitment of cells that are morphologically indistinguishable from stem cells.
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http://dx.doi.org/10.1016/j.celrep.2015.06.011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4518462PMC
July 2015

Complement Regulates Nutrient Influx and Metabolic Reprogramming during Th1 Cell Responses.

Immunity 2015 Jun;42(6):1033-47

Division of Transplant Immunology and Mucosal Biology, MRC Centre for Transplantation, King's College London, Guy's Hospital, Great Maze Pond, London SE1 9RT, UK. Electronic address:

Expansion and acquisition of Th1 cell effector function requires metabolic reprogramming; however, the signals instructing these adaptations remain poorly defined. Here we found that in activated human T cells, autocrine stimulation of the complement receptor CD46, and specifically its intracellular domain CYT-1, was required for induction of the amino acid (AA) transporter LAT1 and enhanced expression of the glucose transporter GLUT1. Furthermore, CD46 activation simultaneously drove expression of LAMTOR5, which mediated assembly of the AA-sensing Ragulator-Rag-mTORC1 complex and increased glycolysis and oxidative phosphorylation (OXPHOS), required for cytokine production. T cells from CD46-deficient patients, characterized by defective Th1 cell induction, failed to upregulate the molecular components of this metabolic program as well as glycolysis and OXPHOS, but IFN-γ production could be reinstated by retrovirus-mediated CD46-CYT-1 expression. These data establish a critical link between the complement system and immunometabolic adaptations driving human CD4(+) T cell effector function.
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http://dx.doi.org/10.1016/j.immuni.2015.05.024DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4518498PMC
June 2015