Central macular morphology and optic nerve fibre layer thickness in young adults born premature and screened for retinopathy of prematurity

Publisher Copyright: © 2023 The Authors. Acta Ophthalmologica published by John Wiley & Sons Ltd on behalf of Acta Ophthalmologica Scandinavica Foundation.Purpose: To investigate central retinal morphology and optic retinal nerve fibre layer (RNFL) in prematurely born young adults and compare to term born controls. Materials and Methods: The participants were 59 prematurely born individuals, with a birthweight ≤1.500 g, and 44 term born controls, all 25–29 years of age. Visual acuity (VA) and contrast sensitivity (CS) were assessed. The retinal macular thickness, ganglion cell-inner plexiform layer (GC-IPL) thickness and RNFL thickness were assessed with Cirrus optical coherence tomography (OCT). Results: Central macular thickness was increased (mean 26.7 μm) in prematurely born individuals compared to controls. The macular GC-IPL was thinner (mean 3.84 μm), also when excluding those with previous retinopathy of prematurity (ROP) and those with neurological complications. Gestational age at birth and previous treatment of ROP were risk factors for a thicker macula, however, not for reduced GC-IPL. The average peripapillary RNFL was thinner (mean 4.61 μm) in the prematurely born individuals, also when excluding those with previous ROP and/or neurological complications. Within the prematurely born group, treated ROP was correlated with increased average RNFL. Further, both better VA and CS were associated with thinner optic nerve RNFL and thicker average GC-IPL. Conclusion: Macular and optic nerve morphology were influenced by premature birth as assessed with OCT in adult individuals. Gestational age at birth and treatment for ROP seemed to affect central macular thickness, and treated ROP affected the peripapillary RNFL. Thus, retinal sequelae remained in adulthood.Peer reviewe

A scalable adenovirus production process, from cell culture to purified bulk

Adenovirus (AdV) vectors are commonly used in cancer gene therapy trials, evaluated in gene therapy and used as vaccines for various diseases. AdV vectors are well studied and are suitable as vaccine vectors due to their ability to infect different cell types, remain episomal and produce stable high titer material. Manufacturing of safe and efficacious clinical-grade virus relies on a scalable and cost-effective production process. In this study, we have combined experimental work and process economy calculations, from AdV production in cell culture to purified bulk product up to 10L scale. An efficient and scalable process for AdV production was developed by evaluation of each process step. The most studied vector is serotype 5, making this a suitable system for process development of AdV vectors. Human AdV5 expressing the green fluorescent protein (GFP) was used for process development. First, suspension HEK 293 cells adapted to serum-free cell culture medium were optimized for AdV production and evaluated in different single use bioreactor systems. Tween 20 was used for cell lysis as a replacement for the traditionally used Triton X-100 (now on the Authorization list (Annex XIV) of REACH, the regulation on Registration, Evaluation, Authorization and restriction of Chemicals). A residual Tween 20 assay with low detection limit was set-up. Filters and conditions for clarification, concentration and buffer exchange by tangential flow filtration were optimized. Anion exchange based capture step alternatives were compared, including different chromatography resins and membrane formats. Finally, core bead technology was evaluated as an alternative to size exclusion chromatography for the polishing step before the final formulation. Analytical methods for virus titer are challenging and depend on purity and quality of the sample. For total virus titer, qPCR and HPLC methods were used. Furthermore, a method based on surface plasmon resonance (Biacore) was developed for analysis of adenovirus titer. For infectious virus titer, we have used a cell based assay with automatic image analysis. Based on analytical data different downstream process alternatives were compared regarding load capacity, recovery and purity and we propose a robust and scalable process with a favorable process economy. Please click Additional Files below to see the full abstract

Design and rationale of FLAVOUR: A phase IIa efficacy study of the 5-lipoxygenase activating protein antagonist AZD5718 in patients with recent myocardial infarction

levels is the primary efficacy outcome. FLAVOUR also aims to evaluate whether AZD5718 can improve coronary microvascular function, as measured by transthoracic colour Doppler-assisted coronary flow velocity reserve. Centrally pretrained study sonographers use standardized protocols and equipment. Additional outcomes include assessment of comprehensive echocardiographic parameters (including coronary flow, global strain, early diastolic strain rate and left ventricular ejection fraction), arterial stiffness, biomarkers, health-related quality of life, and safety. Specific anti-inflammatory therapies may represent novel promising treatments to reduce residual risk in patients with coronary artery disease. By combining primary pharmacodynamic and secondary cardiovascular surrogate efficacy outcomes, FLAVOUR aims to investigate the mechanistic basis and potential benefits of AZD5718 treatment in patients with coronary artery disease

Relations between lipoprotein(a) concentrations, LPA genetic variants, and the risk of mortality in patients with established coronary heart disease: a molecular and genetic association study

Background: Lipoprotein(a) concentrations in plasma are associated with cardiovascular risk in the general population. Whether lipoprotein(a) concentrations or LPA genetic variants predict long-term mortality in patients with established coronary heart disease remains less clear. Methods: We obtained data from 3313 patients with established coronary heart disease in the Ludwigshafen Risk and Cardiovascular Health (LURIC) study. We tested associations of tertiles of lipoprotein(a) concentration in plasma and two LPA single-nucleotide polymorphisms ([SNPs] rs10455872 and rs3798220) with all-cause mortality and cardiovascular mortality by Cox regression analysis and with severity of disease by generalised linear modelling, with and without adjustment for age, sex, diabetes diagnosis, systolic blood pressure, BMI, smoking status, estimated glomerular filtration rate, LDL-cholesterol concentration, and use of lipid-lowering therapy. Results for plasma lipoprotein(a) concentrations were validated in five independent studies involving 10 195 patients with established coronary heart disease. Results for genetic associations were replicated through large-scale collaborative analysis in the GENIUS-CHD consortium, comprising 106 353 patients with established coronary heart disease and 19 332 deaths in 22 studies or cohorts. Findings: The median follow-up was 9·9 years. Increased severity of coronary heart disease was associated with lipoprotein(a) concentrations in plasma in the highest tertile (adjusted hazard radio [HR] 1·44, 95% CI 1·14–1·83) and the presence of either LPA SNP (1·88, 1·40–2·53). No associations were found in LURIC with all-cause mortality (highest tertile of lipoprotein(a) concentration in plasma 0·95, 0·81–1·11 and either LPA SNP 1·10, 0·92–1·31) or cardiovascular mortality (0·99, 0·81–1·2 and 1·13, 0·90–1·40, respectively) or in the validation studies. Interpretation: In patients with prevalent coronary heart disease, lipoprotein(a) concentrations and genetic variants showed no associations with mortality. We conclude that these variables are not useful risk factors to measure to predict progression to death after coronary heart disease is established. Funding: Seventh Framework Programme for Research and Technical Development (AtheroRemo and RiskyCAD), INTERREG IV Oberrhein Programme, Deutsche Nierenstiftung, Else-Kroener Fresenius Foundation, Deutsche Stiftung für Herzforschung, Deutsche Forschungsgemeinschaft, Saarland University, German Federal Ministry of Education and Research, Willy Robert Pitzer Foundation, and Waldburg-Zeil Clinics Isny

Naturens betydelse för barns hälsa

Syftet med denna uppsats var att undersöka naturens betydelse för barns hälsa. På två förskolor har vi undersökt både naturförskolegrupper och traditionella förskolegrupper. Vi valde olika metoder som jämfördes med varandra och litteratur/tidigare forskning. Vi har försökt förstå och tolkat de olika uppgifter vi fått fram via litteratur, barnobservationer, barnintervjuer, pedagogenkäter samt närvarostatistik. Genom dessa har vi fått svar på våra frågor om naturens koppling till barns hälsa och deras möjlighet till rekreation genom leken. Vår data visar att barnen var kreativa och fann harmoni i naturen vilket också litteraturen säger. Likaså fann vi att naturförskolegruppens barn var friskare än den traditionella förskolegruppens barn. Barn mår bra av att vistas i naturen vilket vår studie visar

Normative data and repeatability for macular ganglion cell layer thickness in healthy Swedish children using swept source optical coherence tomography

Background:  Optical coherent tomography (OCT) technology is evolving with improved resolution and accuracy in segmentation between different cell layers in the retina. The ganglion cell layer in the macula region is a window to see what is happening in the visual pathways and a macula OCT is an examination that most children tolerate. This makes updated normative data necessary since variables may differ between different OCT devices and normative data for children is often not presented. The aim of this study was to develop normative data for macular ganglion cell layer thickness in children, measured with swept source OCT, and investigate the repeatability between measurements. Methods: Healthy Swedish children between 4 and 16 years old, with normal refraction, spherical equivalent mean:1.13 (sd:0.66) dioptre and normal visual acuity Logmar, mean: 0,015 (sd:0,05), were examined with swept source OCT. Macula OCT was performed three times in both eyes and the different retinal layers were evaluated. Results: Fifty-eight children were screened for inclusion. Fifty-five children were included in the study, 24 boys and 31 girls. Mean age was 8.9 years. Results from right eyes was analysed. The mean average thickness of macular ganglion cell layer thickness, retinal nerve fibre layer/ganglion cell layer boundary to inner plexiform layer/inner nuclear layer boundary, was 68.0 μm (sd:4.0, range:58-77). There was no correlation with sex or age. Fifty-three children manage to complete two, and 41 children three acceptable measurement and the mean coefficient of variation was low. Conclusion: The ganglion cell layer thickness differs according to which OCT device that is used, and the population examined. This makes normative data essential to accurately interpret results. Swept source OCT of the macula have excellent repeatability and the examination well tolerated in most children making it an investigation useful for diagnosing and following diseases in the optic pathways

Photoreceptor Function in School-Aged Children is Affected by Preterm Birth.

Prematurely born children have affected visual functions at school age. Optical coherent tomography (OCT) has shown morphological changes in the retina, suggesting a disturbance in normal retinal development in these children. The aim of this study was to examine retinal function with fullfield electroretinogram (ffERG) in school-aged children born prematurely and compare with children born at term. A second aim was to correlate retinal function with visual acuity (VA), gestational age (GA), birth weight, and retinopathy of prematurity (ROP)