Ocular surface immune transcriptome and tear cytokines in corneal infection patients

Background: Microbial keratitis is one of the leading causes of blindness globally. An overactive immune response during an infection can exacerbate damage, causing corneal opacities and vision loss. This study aimed to identify the differentially expressed genes between corneal infection patients and healthy volunteers within the cornea and conjunctiva and elucidate the contributing pathways to these conditions’ pathogenesis. Moreover, it compared the corneal and conjunctival transcriptomes in corneal-infected patients to cytokine levels in tears. Methods: Corneal and conjunctival swabs were collected from seven corneal infection patients and three healthy controls under topical anesthesia. RNA from seven corneal infection patients and three healthy volunteers were analyzed by RNA sequencing (RNA-Seq). Tear proteins were extracted from Schirmer strips via acetone precipitation from 38 cases of corneal infection and 14 healthy controls. The cytokines and chemokines IL-1β, IL-6, CXCL8 (IL-8), CX3CL1, IL-10, IL-12 (p70), IL-17A, and IL-23 were measured using an antibody bead assay. Results: A total of 512 genes were found to be differentially expressed in infected corneas compared to healthy corneas, with 508 being upregulated and four downregulated (fold-change (FC) 2 and adjusted p <0.01). For the conjunctiva, 477 were upregulated, and 3 were downregulated (FC <−3 or ≥ 3 and adjusted p <0.01). There was a significant overlap in cornea and conjunctiva gene expression in patients with corneal infections. The genes were predominantly associated with immune response, regulation of angiogenesis, and apoptotic signaling pathways. The most highly upregulated gene was CXCL8 (which codes for IL-8 protein). In patients with corneal infections, the concentration of IL-8 protein in tears was relatively higher in patients compared to healthy controls but did not show statistical significance. Conclusions: During corneal infection, many genes were upregulated, with most of them being associated with immune response, regulation of angiogenesis, and apoptotic signaling. The findings may facilitate the development of treatments for corneal infections that can dampen specific aspects of the immune response to reduce scarring and preserve sight

Inhibitory effects of angiotensin II receptor blockade on human tenon fibroblast migration and reactive oxygen species production in cell culture

Purpose: We investigate the effect of angiotensin receptor blockade on the migration of human Tenon fibroblasts (HTF), using irbesartan, an angiotensin II receptor type 1 (AT1R) blocker (ARB) as a potential antifibrotic agent in glaucoma filtration surgery. Methods: Confluent HTF cultures were scratched with a 1 mL pipette tip and treated with either irbesartan (10, 50, and 100 μg/mL) or angiotensin II (2 μg/mL). The extent of HTF migration up to 30 hours, and cell number and morphology at 72 hours was evaluated. To assess the effect on reactive oxygen species (ROS) level, HTF were treated with either irbesartan (10 μg/mL) or angiotensin II (2 μg/mL) for 24 hours after scratching, and then stained with dihydroethidium (DHE) before evaluation by confocal microscopy. Results: Irbesartan inhibited HTF migration by 50% to 70% compared to controls (P < 0.05). Levels of ROS were almost completely attenuated by irbesartan (DHE fluorescence intensity of 5.68E-09) (P < 0.05). Irbesartan reduced cell numbers by 50% and induced morphologic changes with loss of pseudopods (P < 0.05). Conversely, angiotensin II increased cell numbers up to 4-fold while retaining cell viability. Conclusions: Irbesartan inhibited HTF migration and ROS production. It also reduced cell numbers and altered HTF morphology. Angiotensin II increased cell number without altering morphology. This initial study warrants future investigations for further potential antifibrotic effects of this drug. Translational Relevance: This in vitro study focused on investigations of irbesartan’s effects on HTF migration, ROS production, as well as HTF cell numbers and morphology. It suggests a potential therapeutic strategy worth further exploration with a view towards postoperative wound healing modulation in glaucoma filtration surgery

Can the appropriateness of eye care be measured through cross-sectional retrospective patient record review in eye care practices in Australia? the icaretrack feasibility study

© Author(s) (or their employer(s)) 2018. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ. Objectives The CareTrack study found that a wide range of appropriateness of care (ie, care in line with evidence-based or consensus-based guidelines) was delivered across many health conditions in Australia. This study therefore aimed to demonstrate the feasibility of using the CareTrack method (a retrospective onsite record review) to measure the appropriateness of eye care delivery. Design Cross-sectional feasibility study. Setting and participants Two hundred and thirteen patient records randomly selected from eight optometry and ophthalmology practices in Australia, selected through a combination of convenience and maximum variation sampling. Methods Retrospective record review designed to assess the alignment between eye care delivered and 93 clinical indicators (Delphi method involving 11 experts) extracted from evidence-based clinical practice guidelines. Primary outcome measure Number of eligible patient records, sampling rates and data collection time. This feasibility study also tested the ability of 93 clinical indicators to measure percentage appropriate eye care for preventative, glaucoma and diabetic eye care. A secondary outcome was the percentage of practitioner-patient encounters at which appropriate eye care was received. Results A median of 20 records (range 9 to 63) per practice were reviewed. Data collection time ranged from 3 to 5.5 hours (median 3.5). The most effective sampling strategy involved random letter generation followed by sequential sampling. The appropriateness of care was 69% (95% CI 67% to 70%) for preventative eye care, 60% (95% CI 56% to 58%) for glaucoma and 63% (95% CI 57% to 69%) for diabetic eye care. Conclusions Appropriateness of eye care can be measured effectively using retrospective record review of eye care practices and consensus-based care indicators

Acupressure for smoking cessation – a pilot study

BACKGROUND: Tobacco smoking is a serious risk to health: several therapies are available to assist those who wish to stop. Smokers who approach publicly funded stop-smoking clinics in the UK are currently offered nicotine replacement therapy (NRT) or bupropion, and group behaviour therapy, for which there is evidence of effectiveness. Acupuncture and acupressure are also used to help smokers, though a systematic review of the evidence of their effectiveness was inconclusive. The aim of this pilot project was to determine the feasibility of a study to test acupressure as an adjunct to one anti-smoking treatment currently offered, and to inform the design of the study. METHODS: An open randomised controlled pilot study was conducted within the six week group programme offered by the Smoking Advice Service in Plymouth, UK. All participants received the usual treatment with NRT and group behavioural therapy, and were randomised into three groups: group A with two auricular acupressure beads, group B with one bead, and group C with no additional therapy. Participants were taught to press the beads when they experienced cravings. Beads were worn in one ear for four weeks, being replaced as necessary. The main outcome measures assessed in the pilot were success at quitting (expired CO ≤ 9 ppm), the dose of NRT used, and the rating of withdrawal symptoms using the Mood and Symptoms Scale. RESULTS: From 49 smokers attending four clinics, 24 volunteered to participate, 19 attended at least once after quitting, and seven remained to the final week. Participants who dropped out reported significantly fewer previous quit attempts, but no other significant differences. Participants reported stimulating the beads as expected during the initial days after quitting, but most soon reduced the frequency of stimulation. The discomfort caused by the beads was minor, and there were no significant side effects. There were technical problems with adhesiveness of the dressing. Reporting of NRT consumption was poor, with much missing data, but reporting of ratings of withdrawal symptom scores was nearly complete. However, these showed no significant changes or differences between groups for any week. CONCLUSION: Any effects of acupressure on smoking withdrawal, as an adjunct to the use of NRT and behavioural intervention, are unlikely to be detectable by the methods used here and further preliminary studies are required before the hypothesis can be tested

Contact metamorphism associated to the Penamacor - Monsanto granitic intrusion (Central Portugal): geochemical, isotopic and mineralogical features

Contact metamorphism related to Variscan and late-Variscan granitic plutons in the Iberian Peninsula is superimposed on medium-grade regional metamorphism, making it often difficult to evaluate per se the thermal effects due to those intrusions and explaining the paucity of scientific literature on the subject. An exhaustive set of geochemical, isotopic and mineralogical data on the contact-zone metasediments hosting the Penamacor-Monsanto granite (Central Iberian Zone, Portugal) provides a significant contribution to the characterization of low- to intermediate-grade contact metamorphism in geological contexts formerly affected by regional metamorphism. The metasediments hosting the Penamacor-Monsanto pluton belong to the extensive detrital sequence of the ante-Ordovician Schist-Greywacke Complex. Bulk geochemistry, oxygen isotope data and crystal-chemistry of key minerals from those contact-zone and neighbouring metasediments have made it possible to infer metamorphic conditions on the contact zone of this granitic intrusion, and to distinguish them from late boron-metasomatism at the exocontact. Mineral paragenesis (muscovite + biotite + chlorite quartz plagioclase cordierite, in spotted-schists; biotite + chlorite quartz plagioclase ( cordierite), in hornfelses) and the composition of these coexisting mineral phases indicate that most of the contact rocks reached the biotite zone (or even the cordierite zone, in some cases), equivalent to upper greenschist – lower amphibolite metamorphic grade. The relatively narrow range of O-isotope temperatures estimated for the crystallization of the marginal granites (550-625ºC) explains the absence of significant effects of thermal flow anisotropy on the contact-zone rocks. Besides, textural, paragenetic, mineralogical, isotopic and geochemical nuances observed in hornfelses and spotted-schists seem mainly related to the local host-rock heterogeneities, rather than to thermal effects. The relatively low temperatures estimated for granitoid emplacement and their restricted isotopic and mineralogical impacts on the metasedimentary host-rocks account for the narrow metamorphic aureole associated with the Penamacor-Monsanto pluton, and suggest this massif may correspond to the outcropping tip of a larger granitic intrusion at depth.Las intrusions graníticas Varíscicas y tardivaríscicas de la Península Ibérica dieron lugar a un metamorfsmo de contacto que afecta a un encajante previamente sometido a un metamorfsmo regional de grado medio, lo que difculta separar los efectos térmicos de aquellos regionales, y explica la escasez de estudios sobre el mismo. El estudio detallado de la zona de contacto entre el Granito de Penamacor-Monsanto (Zona Centro-Ibérica; Portugal) y su encajante metasedimentario mediante técnicas geoquímicas, mineralógicas e isotópicas supone una notable contribución al conocimiento y caracterización del metamorfsmo de contacto de grados bajos a intermedios en contextos geológicos previamente afectados por metamorfsmo regional. El encajante metasedimentario del Plutón de Penamacor-Monsanto es parte de la amplia secuencia detrítica ante-Ordovícia conocida como Complejo Esquisto-Grawackico. Datos geoquímicos de roca total y cristaloquímicos de los minerales más característicos, y relaciones isotópicas de oxígeno en la zona de contacto y metasedimentos aledaños permiten inferir las condiciones metamórfcas en la zona de contacto de dicha intrusión, y diferenciarla de aquella afectada por metasomatismo tardío por B. La paragénesis mineral (muscovita + biotita + clorita ± cuarzo ± plagioclasa ± cordierita en los esquistos moteados; biotita + clorita ± cuarzo ± plagiclasa (± cordierita) en corneanas) y la composición de las fases minerales coexistentes indican que la mayoría de rocas del contacto alcanzaron la zona de la biotita (e incluso, en algunos casos, aquella de la cordierita), equivalente a la parte alta del grado metamórfco de los esquistos verdes, o a la parte baja de las anfbolitas. El rango relativamente pequeño de temperaturas de cristalización de los granitos marginales (550-625°C), calculado mediante isótopos de oxígeno, explica la carencia de anisotropías térmicas signifcativas en las rocas del contacto. Las sutiles diferencias texturales, paragenéticas, mineralógicas, isotópicas y geoquímicas en esquistos moteados y corneanas parecen relacionadas con heterogeneidades locales de los encajantes, y no con efectos térmicos diferenciados. Las temperaturas relativamente bajas estimadas durante la intrusión del granito de Penamacor-Monsanto, y el limitado efecto mineralógico e isotópico sobre el encajante metasedimentario, dan lugar a una aureola de contacto estrecha, y sugieren que este macizo puede corresponder al techo de una intrusión mayor en profundidad.Funding was provided by FCT—Fundação para a Ciên cia e Tecnologia, through project METMOB (PTDC/CTE-GIX/116204/2009

Post-orogenic shoshonitic magmas of the Yzerfontein pluton, South Africa: the 'smoking gun' of mantle melting and crustal growth during Cape granite genesis?

The post-orogenic Yzerfontein pluton, in the Saldania Belt of South Africa was constructed through numerous injections of shoshonitic magmas. Most magma compositions are adequately modelled as products of fractionation, but the monzogranites and syenogranites may have a separate origin. A separate high-Mg mafic series has a less radiogenic mantle source. Fine-grained magmatic enclaves in the intermediate shoshonitic rocks are autoliths. The pluton was emplaced between 533 ± 3 and 537 ± 3 Ma (LASF-ICP-MS U–Pb zircon), essentially synchronously with many granitic magmas of the Cape Granite Suite (CGS). Yzerfontein may represent a high-level expression of the mantle heat source that initiated partial melting of the local crust and produced the CGS granitic magmas, late in the Saldanian Orogeny. However, magma mixing is not evident at emplacement level and there are no magmatic kinships with the I-type granitic rocks of the CGS. The mantle wedge is inferred to have been enriched during subduction along the active continental margin. In the late- to post-orogenic phase, the enriched mantle partially melted to produce heterogeneous magma batches, exemplified by those that formed the Yzerfontein pluton, which was further hybridized through minor assimilation of crustal materials. Like Yzerfontein, the small volumes of mafic rocks associated with many batholiths, worldwide, are probably also lowvolume, high-level expressions of crustal growth through the emplacement of major amounts of mafic magma into the deep crust.IS