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

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

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

Constraints on the χ_(c1) versus χ_(c2) polarizations in proton-proton collisions at √s = 8 TeV

The polarizations of promptly produced χ_(c1) and χ_(c2) mesons are studied using data collected by the CMS experiment at the LHC, in proton-proton collisions at √s=8  TeV. The χ_c states are reconstructed via their radiative decays χ_c → J/ψγ, with the photons being measured through conversions to e⁺e⁻, which allows the two states to be well resolved. The polarizations are measured in the helicity frame, through the analysis of the χ_(c2) to χ_(c1) yield ratio as a function of the polar or azimuthal angle of the positive muon emitted in the J/ψ → μ⁺μ⁻ decay, in three bins of J/ψ transverse momentum. While no differences are seen between the two states in terms of azimuthal decay angle distributions, they are observed to have significantly different polar anisotropies. The measurement favors a scenario where at least one of the two states is strongly polarized along the helicity quantization axis, in agreement with nonrelativistic quantum chromodynamics predictions. This is the first measurement of significantly polarized quarkonia produced at high transverse momentum