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Juvenile-onset lupus nephritis (LN) affects up to 80% of juvenile-onset systemic lupus erythematosus patients (JSLE). As the exact role of human renal glomerular endothelial cells (GEnCs) in LN has not been fully elucidated, the aim of this study was to investigate their involvement in LN. Conditionally immortalised human GEnCs (ciGEnCs) were treated with pro-inflammatory cytokines known to be involved in LN pathogenesis and also with LPS. Secretion and surface expression of pro-inflammatory proteins was quantified via ELISA and flow cytometry. NF-κΒ and STAT-1 activation was investigated via immunofluorescence. Serum samples from JSLE patients and from healthy controls were used to treat ciGEnCs to determine via qRT-PCR potential changes in the mRNA levels of pro-inflammatory genes. Our results identified TNF-α, IL-1β, IL-13, IFN-γ and LPS as robust in vitro stimuli of ciGEnCs. Each of them led to significantly increased production of different pro-inflammatory proteins, including; IL-6, IL-10, MCP-1, sVCAM-1, MIP-1α, IP-10, GM-CSF, M-CSF, TNF-α, IFN-γ, VCAM-1, ICAM-1, PD-L1 and ICOS-L. TNF-α and IL-1β were shown to activate NF-κB, whilst IFN-γ activated STAT-1. JSLE patient serum promoted IL-6 and IL-1β mRNA expression. In conclusion, our in vitro model provides evidence that human GEnCs play a pivotal role in LN-associated inflammatory process.

Purpose: To report on the composition and performance of the portfolio of Ophthalmology research studies in the United Kingdom's National Institute for Health Research (NIHR) Clinical Research Network (UK CRN)., Methods: Ophthalmology studies open to recruitment between 1 April 2010 and 31 March 2018 were classified by: sub-specialty, participant age, gender of Chief Investigator, involvement of genetic investigations, commercial/ non-commercial, interventional/observational design. Frequency distributions for each covariate and temporal variation in recruitment to time and target were analysed., Results: Over 8 years, 137,377 participants were recruited (average of 15,457 participants/year; range: 5485-32,573) with growth by year in proportion of commercial studies and hospital participation in England (76% in 2017/18). Fourteen percent of studies had a genetic component and most studies (82%) included only adults. The majority of studies (41%) enrolled patients with retinal diseases, followed by glaucoma (17%), anterior segment and cataract (13%), and ocular inflammation (6%). Overall, 68% of non-commercial studies and 55% of commercial studies recruited within the anticipated time set by the study and also recruited to or exceeded the target number of participants., Conclusions: High levels of clinical research activity, growth and improved performance have been observed in Ophthalmology in UK over the past 8 years. Some sub-specialties that carry substantial morbidity and a very high burden on NHS services are underrepresented and deserve more patient-centred research. Yet the NIHR and its CRN Ophthalmology National Specialty Group has enabled key steps in achieving the goal of embedding research into every day clinical care.

Background: Optimising home oxygen delivery in infants has important logistical and safety implications. This can be aided by having a suitable reference range of normal values for arterial oxygen saturation using pulse oximetry (SpO(2))., Objectives: To describe oxygenation profiles in healthy preterm and term infants in relation to gestational and postnatal age, to extend reference values to guide home oxygen therapy., Study Design: Prospective monitoring of SpO(2) for 4 hours at 3 monthly intervals of 34 term, and 53 preterm healthy infants, took place over a 12-month period using an Ohmeda Biox 3700e pulse oximeter and data logger., Results: Group mean and 5th percentiles were used to construct cumulative frequency curves at each time interval, representing the normal reference range of SpO(2) profiles for term and preterm infants over time., Conclusions: These data may be used to test the benefits in the home or hospital of having a reference range of normal values for cumulative SpO(2).

Surfactant proteins (SPs) play an important role in surfactant metabolism and function. Understanding their relative contribution to clinical outcome remains incomplete. Exogenous surfactants differ in their SP content and physiologic effects. The aims of this study were to measure bronchoalveolar lavage (BAL) SP concentrations from preterm infants ventilated for respiratory distress syndrome and to assess their association with clinical outcome. Fifty preterm infants randomized to receive a natural or synthetic surfactant were lavaged each day for the first week and twice weekly thereafter using a standardized nonbronchoscopic technique. BAL SP-A, SP-B, and SP-D concentrations were measured using ELISA. Median BAL SP-A, SP-B, and SP-D concentrations for the whole cohort rose significantly during the first postnatal week (p < 0.05). SP-A concentration did not differ between outcome groups. BAL SP-B concentration rose significantly in lungs that were not supplemented with SP-B. Infants dying had significantly lower BAL SP-B concentrations on d 2 and 6 compared with survivors. BAL SP-D concentrations were significantly lower on d 2 and 3 among infants in supplemental oxygen on d 28 compared with those in air. BAL SP-A and SP-D concentrations did not differ significantly between infants randomized to receive a natural or synthetic surfactant. Lower BAL SP-B and SP-D but not SP-A concentrations were associated with worse clinical prognosis.

Pro-inflammatory cytokines such as IL-8 play an important role in the inflammatory response to neonatal airway injury. Difficulty in detecting counter-regulatory cytokines such as IL-10 in lavage fluid from preterm infants led to the suggestion that its deficit may be a factor in the etiology of chronic lung disease of prematurity (CLD). The aim of the study was to determine IL-8 and IL-10 concentrations in lavage fluid from preterm infants ventilated for respiratory distress syndrome. Fifty infants <30 wk gestation were studied who had been randomized to receive a natural or synthetic surfactant. Lavage samples were collected daily for the first week and twice weekly thereafter. Samples were immediately centrifuged and stored at -70 degrees C. Cytokine concentrations were quantified in duplicate using commercially available sandwich ELISA kits. Lavage IL-10 concentration, at a minimum initially, rose significant over the first five postnatal days (p = 0.009). In the same samples, lavage IL-8 concentrations rose significantly over the first postnatal week (p < 0.001), the rise preceding that of IL-10. Infants dying or developing CLD had a significant early rise in both cytokine concentrations. Compared with infants developing CLD, lavage IL-10 concentrations were significantly higher on d 1 among those not developing CLD but significantly lower on d 4 (p < 0.05). To conclude, IL-10 is detectable in lavage fluid from ventilated preterm infants and its concentrations rise significantly over the first five postnatal days. In the same samples, IL-8 concentration also rises and this increase precedes the rise in IL-10.