572 research outputs found
Conjunctival cytokine expression in symptomatic moderate dry eye subjects
PURPOSE. To compare ocular surface cytokine expression in healthy controls and subjects with moderate dry eye and to study the ability of interleukin (IL)-1 to modulate cytokine expression in cultured human conjunctival epithelial cells (CECs). METHODS. Subjective (symptom questionnaire) and objective (tear osmolality, fluorescein tear break-up time [TBUT]) measures of dry eye were determined in five healthy controls and five subjects with moderate dry eye. Tear clearance rates were measured with a fluorophotometer. Enzyme immunoassay and a cytokine bead assay were used to quantify IL-1 in tear fluid. RT-PCR was performed to detect expression of IL-1, IL-6, IL-8, growth-related oncogene (GRO)-, intercellular adhesion molecule (ICAM)-1, tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), and ephrin A5 in conjunctival impression cytology (CIC) samples and in CECs (IOBA-NHC cell line, n ϭ 3; primary cultured CEC, n ϭ 3) exposed to 10 ng/mL IL-1 for 6 hours. RESULTS. Subjects with moderate dry eye had significantly higher symptom scores, higher tear osmolality, and shorter TBUT than healthy controls. Subjects with dry eye demonstrated slightly slower tear clearance (13.1% per minute) than healthy controls (15.4% per minute). Very low levels of IL-1 protein were detected in the tear fluid of both groups. TRAIL was constitutively expressed in CIC samples, whereas IL-1, IL-6, and GRO- were absent. Weak expression of IL-8 (two healthy, four dry eye), ICAM-1 (four healthy, four dry eye), and ephrin A5 (one healthy, two dry eye) was observed. IL-1 upregulated its own expression and that of IL-6, IL-8, GRO-, and ICAM-1 in cultured CECs but not that of ephrin A5 or TRAIL. CONCLUSIONS. The lack of major differences in ocular surface cytokine expression between the two groups of subjects implies other inflammatory pathways or etiologies are involved in moderate dry eye. Although IL-1 modulated the expression of various cytokines in cultured CECs, its absence in tear fluid and CIC samples suggests that IL-1 does not play a modulatory role in moderate dry eye. (Invest Ophthalmol Vis Sci
"Including us, talking to us and creating a safe environment" - Youth Patient & Public Involvement and the Walking In ScHools (WISH) Study: Lessons learned
© 2023 The authors. This is an open access article available under a Creative Commons licence. The published version can be accessed at the following link on the publisher’s website: https://doi.org/10.1111/hex.13885Background: Young people have the right to be informed and consulted about decisions affecting their lives. Patient and public involvement (PPI) ensures that research is carried out ‘with’ or ‘by’ young people rather than ‘to’, ‘about’ or ‘for’ them. The aim of this paper is to outline how youth PPI can be embedded within a physical activity intervention, reflect on the impact of PPI and provide recommendations for future PPI in a similar context. Methods: A Youth Advisory Group (YAG) was set up within the Walking In ScHools (WISH) Study to involve adolescent girls in the delivery, implementation and dissemination of a physical activity intervention targeted at adolescents. Schools invited pupils aged 12–14 years and 15–18 years to YAG meetings (n3, from 2019 to 2023). Participative methods were used to inform recruitment strategies and data collection methods for the WISH Study. Results: Across the three YAG meetings, n51 pupils from n8 schools were involved. Pupils enjoyed the YAG meetings, felt that their feedback was valued and considered the meetings a good way to get young people involved in research. The YAG advised on specific issues and although measuring impact was not the primary aim of the YAG meetings, over the course of the study there were many examples of the impact of PPI. Recruitment targets for the WISH Study were exceeded, the attrition rate was low and pupils were engaged in data collection. Conclusion: Youth PPI is a developing field and there are few physical activity studies that report the PPI work undertaken. Within the WISH Study, three YAG meetings were held successfully, and the views of adolescent girls were central to the development of the study. Considering the specific issues that the YAG advised on (study recruitment, attrition and data collection), there was evidence of a positive impact of PPI. Patient or Public Contribution: Pupils from post-primary schools interested/participating in the WISH Study were invited to attend YAG meetings. YAG meetings were set up to consult adolescent girls on the delivery, implementation and dissemination of the WISH intervention.The WISH Study was funded from INTERREG VA funding of €8.84m (including a 15% contribution from the Department of Health in NI and Republic of Ireland), which had been awarded to the HSC Research & Development Division of the Public Health Agency Northern Ireland and to the Health Research Board in Ireland for the Cross-border Healthcare Intervention Trials in Ireland Network project.Published versio
Implementation and evaluation of the Walking In ScHools (WISH) Trial in adolescent girls: mixed-methods process evaluation of a clustered randomised control trial using RE-AIM
Key findings from The Walking In ScHools (WISH) Study, a peer-led walking intervention for adolescent girls
Project Description: The effects of walking interventions on adult health are known, however the potential of walking to promote physical activity (PA) in adolescents is less known. This study evaluated the effectiveness of a novel, school-based walking intervention at increasing PA levels of adolescent girls. Female pupils aged 12-14 years, were recruited from eighteen (mixed or single-sex) schools across the Border Region of Ireland/Northern Ireland. Schools were randomised to control (usual physical activity; n9) or intervention (n9). In intervention schools, female pupils (15-18 years) were trained as walk leaders and led the younger pupils in 10-15min walks before school, at break and lunchtime. Walks were in school grounds and pupils were encouraged to join as many walks as possible. Excluding holidays, the intervention was delivered for a full school year (18-21 weeks). Accelerometers measured PA and the primary outcome was total PA (cpm). Impact: In total, 589 pupils were recruited (intervention: n286; control n303). Baseline moderate-vigorous PA (MVPA) for the intervention group was (median [IQR]) 36.1 (23.0) mins per day and 35.3 (19.8) mins per day in the control group. At baseline, only 15% (n37) of intervention and 10% (n29) of control participants met PA guidelines (60 mins MVPA per day). Post-intervention total PA (cpm) did not statistically differ between groups when adjusted for age, body mass index z-scores and baseline PA (mean difference, -33.5, 95% CI= -21.2 to 88.1; p=0.213). Learning: ‘Scaling-up’ PA interventions is challenging. Despite a promising feasibility study, the results of this fully powered trial indicate that in this context, the walking programme did not increase PA. Since the COVID-19 pandemic, school environments have changed and although pupils enjoyed the programme, attendance at walks was low. There is a need to better understand the implementation of interventions such as WISH within schools
The effectiveness of a peer-led school-based walking intervention on adolescent girls’ physical activity: the Walking In ScHools (WISH) study
S06-5 The Walking In ScHools (WISH) study: Development and evaluation of a peer-led school-based walking intervention in adolescent girls from pilot to fully-powered trial
BACKGROUND: Walking interventions, delivered within the school setting, have the potential to increase physical activity (PA) in adolescents. Previous research has shown that walking is an acceptable form of PA for adolescent girls, and that walking interventions may be effective at increasing PA in this group. Findings from the Walking In ScHools (WISH) pilot study (n199 female participants) found the intervention was effective in increasing light intensity PA in adolescent girls, but further research is needed to examine the effects of walking on overall PA and the role of peer leaders in delivering school-based interventions. The present study aims to build upon this pilot work and evaluate the effectiveness of a novel, low-cost, peer-led school-based walking intervention, delivered across the school year, at increasing accelerometer-measured PA levels of adolescent girls. METHODS: The WISH study is a school-based cluster randomised controlled trial targeting adolescent girls (aged 12-14 years) within the post-primary school setting. Data will be collected at four timepoints, baseline, mid-intervention, post-intervention, and 13 months post-baseline. Following baseline data collection, schools were randomly allocated to intervention (n = 9) or control (n = 9). In intervention schools, older pupils (aged 15-18 years) were trained as walk leaders and led the younger girls in 10-15min walks before school, at break, and during lunch, across the school year (20-22 weeks). The primary outcome measure is accelerometer-measured total PA (post-intervention) and secondary outcomes include anthropometry measures, and wellbeing. RESULTS: Some 590 participants (mean(SD) age 12.6(0.64)years) were recruited from 18 schools across Northern Ireland (n = 9) and the Border region of the Republic of Ireland (n9). Within the intervention schools, 149 walk leaders were trained. At baseline (n = 535), mean(SD) time spent in moderate to vigorous PA (MVPA) was 39.2(17.07)mins/day and 66 (12%) girls achieved PA guidelines of 60 minutes MVPA per day. Data collection and analysis is ongoing. CONCLUSIONS: This research has outlined the development of a novel, peer-led walking intervention and demonstrated its effectiveness at increasing light intensity PA in adolescent girls. The ongoing fully powered trial will build upon this pilot work and further evaluate the effects of the WISH study on increasing PA in adolescent girls
S06-5 The Walking In ScHools (WISH) study:Development and evaluation of a peer-led school-based walking intervention in adolescent girls from pilot to fully-powered trial
Emergency Admissions for Cardiovascular and Respiratory Diseases and the Chemical Composition of Fine Particle Air Pollution
Novel Peptides with Dual Properties for Treating Pseudomonas aeruginosa Keratitis::Antibacterial and Corneal Wound Healing
The corneal epithelium is a layer in the anterior part of eye that contributes to light refraction onto the retina and to the ocular immune defense. Although an intact corneal epithelium is an excellent barrier against microbial pathogens and injuries, corneal abrasions can lead to devastating eye infections. Among them, Pseudomonas aeruginosa-associated keratitis often results in severe deterioration of the corneal tissue and even blindness. Hence, the discovery of new drugs able not only to eradicate ocular infections, which are often resistant to antibiotics, but also to elicit corneal wound repair is highly demanded. Recently, we demonstrated the potent antipseudomonal activity of two peptides, Esc(1-21) and its diastereomer Esc(1-21)-1c. In this study, by means of a mouse model of P. aeruginosa keratitis and an in vivo corneal debridement wound, we discovered the efficacy of these peptides, particularly Esc(1-21)-1c, to cure keratitis and to promote corneal wound healing. This latter property was also supported by in vitro cell scratch and ELISA assays. Overall, the current study highlights Esc peptides as novel ophthalmic agents for treating corneal infection and injury, being able to display a dual function, antimicrobial and wound healing, rarely identified in a single peptide at the same micromolar concentration range
A genome-wide association study identifies protein quantitative trait loci (pQTLs)
There is considerable evidence that human genetic variation influences gene expression. Genome-wide studies have revealed that mRNA levels are associated with genetic variation in or close to the gene coding for those mRNA transcripts - cis effects, and elsewhere in the genome - trans effects. The role of genetic variation in determining protein levels has not been systematically assessed. Using a genome-wide association approach we show that common genetic variation influences levels of clinically relevant proteins in human serum and plasma. We evaluated the role of 496,032 polymorphisms on levels of 42 proteins measured in 1200 fasting individuals from the population based InCHIANTI study. Proteins included insulin, several interleukins, adipokines, chemokines, and liver function markers that are implicated in many common diseases including metabolic, inflammatory, and infectious conditions. We identified eight Cis effects, including variants in or near the IL6R (p = 1.8×10 -57), CCL4L1 (p = 3.9×10-21), IL18 (p = 6.8×10-13), LPA (p = 4.4×10-10), GGT1 (p = 1.5×10-7), SHBG (p = 3.1×10-7), CRP (p = 6.4×10-6) and IL1RN (p = 7.3×10-6) genes, all associated with their respective protein products with effect sizes ranging from 0.19 to 0.69 standard deviations per allele. Mechanisms implicated include altered rates of cleavage of bound to unbound soluble receptor (IL6R), altered secretion rates of different sized proteins (LPA), variation in gene copy number (CCL4L1) and altered transcription (GGT1). We identified one novel trans effect that was an association between ABO blood group and tumour necrosis factor alpha (TNF-alpha) levels (p = 6.8×10-40), but this finding was not present when TNF-alpha was measured using a different assay , or in a second study, suggesting an assay-specific association. Our results show that protein levels share some of the features of the genetics of gene expression. These include the presence of strong genetic effects in cis locations. The identification of protein quantitative trait loci (pQTLs) may be a powerful complementary method of improving our understanding of disease pathways. © 2008 Melzer et al
- …