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Achim Fieß,1,* Sandra Gißler,1,* Philipp S Wild,2– 4 Karl J Lackner,5 Thomas Münzel,6 Matthias Michal,7 Michael S Urschitz,8 Norbert Pfeiffer,1 Alexander K Schuster1 1Department of Ophthalmology, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany; 2Preventive Cardiology and Preventive Medicine - Center for Cardiology, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany; 3Center for Thrombosis and Hemostasis (CTH), University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany; 4German Center for Cardiovascular Research (DZHK), Partner Site Rhine-Main, Mainz, Germany; 5Institute of Clinical Chemistry and Laboratory Medicine, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany; 6Center for Cardiology – Cardiology I, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany; 7Department of Psychosomatic Medicine and Psychotherapy, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany; 8Division of Pediatric Epidemiology, Institute for Medical Biostatistics, Epidemiology and Informatics, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany*These authors contributed equally to this workCorrespondence: Achim Fieß, Department of Ophthalmology, University Medical Center of the Johannes Gutenberg University Mainz, Langenbeckstr. 1, Mainz, 55131, Germany, Tel +49-6131-17-5150, Fax +49-6131-17-8495, Email Achim.fiess@gmail.comAbstract: This study investigates the association between self-reported birth weight (BW) and the prevalence of hypertensive retinopathy (HR) in a large population-based cohort in Germany, as part of the Gutenberg Health Study (GHS). The study involved analyzing fundus photographs of 6855 participants, aged 35 to 74, to assess signs of HR, classified according to the Mitchell-Wong Classification. The research aimed to explore the correlation between fetal growth restriction indicated by BW and the frequency of HR. The results showed that the frequency of HR did not significantly differ among groups with different BW ranges. In the univariable analysis, HR was initially associated with high BW, but this association disappeared after adjusting for age, sex, and cardiovascular risk factors. No association was found between low BW and HR. The study reveals novel insights as there are no prior population-based studies specifically exploring this association.Keywords: birth weight, hypertensive retinopathy, epidemiology, population-based study

Achim Fieß,1 Marilena Brandt,1 Eva Mildenberger,2 Michael Siegfried Urschitz,3 Felix Mathias Wagner,1 Stephanie Desiree Grabitz,1 Esther Maria Hoffmann,1 Norbert Pfeiffer,1 Alexander Konrad Schuster1 1Department of Ophthalmology, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany; 2Division of Neonatology, Department of Pediatrics, University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany; 3Division of Pediatric Epidemiology, Institute for Medical Biostatistics, Epidemiology and Informatics, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, GermanyCorrespondence: Achim Fieß, Department of Ophthalmology, Medical Center of the Johannes Gutenberg University Mainz, Langenbeckstr. 1, Mainz, 55131, Germany, Tel +49-6131-17-5150, Fax +49-6131-17-8495, Email Achim.fiess@gmail.comPurpose: Prenatal growth restriction is associated with impaired neurodevelopment in childhood. This study investigated the effects of being born small for gestational age (SGA) on peripapillary retinal nerve fiber layer (pRNFL) thickness in adults born at term.Methods: A retrospective cohort study was conducted with a prospective ophthalmologic examination of participants born at full-term (gestational age ≥ 37 weeks) between 1969 and 2002. All participants were examined with spectral-domain optical coherence tomography and grouped according to their birth weight in correlation to gestational age as former moderate (birth weight (BW) percentile 3rd to < 10th) and severe SGA (< 3rd percentile), normal (10th-90th percentile, AGA), and moderately (> 90th to 97th percentile) and severely (> 97th percentile) large for gestational age (LGA) adults (18 to 52 years).Results: Overall, 547 eyes of 285 individuals (age 29.9± 9.4 years, 151 females) born at term were included. Multivariable regression analyses revealed a strong association between a lower global pRNFL thickness in the severe SGA (B=− 8.99 [95%-CI: − 12.68; − 5.30] μm; p< 0.001) and in the moderate SGA groups (B=− 6.40 [95%-CI: − 10.29; − 2.50] μm; p=0.001) compared to the reference AGA group.Conclusion: Our results indicate that restricted fetal growth affects neurologic tissue development of the optic nerve head, particularly in individuals born severely SGA at term. This indicates that fetal growth restriction may exert disturbances in the development of neurologic tissue, which persists in adulthood.Keywords: birth weight, small for gestational age, large for gestational age, peripapillary retinal nerve fiber layer, optic nerve head, epidemiology

We present structure and equation of state (EOS) measurements of biaxially orientated polyethylene terephthalate (PET, [Formula: see text], also called mylar) shock-compressed to ([Formula: see text]) GPa and ([Formula: see text]) K using in situ X-ray diffraction, Doppler velocimetry, and optical pyrometry. Comparing to density functional theory molecular dynamics (DFT-MD) simulations, we find a highly correlated liquid at conditions differing from predictions by some equations of state tables, which underlines the influence of complex chemical interactions in this regime. EOS calculations from ab initio DFT-MD simulations and shock Hugoniot measurements of density, pressure and temperature confirm the discrepancy to these tables and present an experimentally benchmarked correction to the description of PET as an exemplary material to represent the mixture of light elements at planetary interior conditions.

The gas and ice giants in our solar system can be seen as a natural laboratory for the physics of highly compressed matter at temperatures up to thousands of kelvins. In turn, our understanding of their structure and evolution depends critically on our ability to model such matter. One key aspect is the miscibility of the elements in their interiors. Here, we demonstrate the feasibility of X-ray Thomson scattering to quantify the degree of species separation in a 1:1 carbon-hydrogen mixture at a pressure of ~150 GPa and a temperature of ~5000 K. Our measurements provide absolute values of the structure factor that encodes the microscopic arrangement of the particles. From these data, we find a lower limit of [Formula: see text]% of the carbon atoms forming isolated carbon clusters. In principle, this procedure can be employed for investigating the miscibility behaviour of any binary mixture at the high-pressure environment of planetary interiors, in particular, for non-crystalline samples where it is difficult to obtain conclusive results from X-ray diffraction. Moreover, this method will enable unprecedented measurements of mixing/demixing kinetics in dense plasma environments, e.g., induced by chemistry or hydrodynamic instabilities.

© 2018 Author(s). Diamond formation in polystyrene (C8H8)n, which is laser-compressed and heated to conditions around 150 GPa and 5000 K, has recently been demonstrated in the laboratory [Kraus et al., Nat. Astron. 1, 606-611 (2017)]. Here, we show an extended analysis and comparison to first-principles simulations of the acquired data and their implications for planetary physics and inertial confinement fusion. Moreover, we discuss the advanced diagnostic capabilities of adding high-quality small angle X-ray scattering and spectrally resolved X-ray scattering to the platform, which shows great prospects of precisely studying the kinetics of chemical reactions in dense plasma environments at pressures exceeding 100 GPa.

© 2017 The Author(s). The effects of hydrocarbon reactions and diamond precipitation on the internal structure and evolution of icy giant planets such as Neptune and Uranus have been discussed for more than three decades1. Inside these celestial bodies, simple hydrocarbons such as methane, which are highly abundant in the atmospheres2, are believed to undergo structural transitions3,4that release hydrogen from deeper layers and may lead to compact stratified cores5-7. Indeed, from the surface towards the core, the isentropes of Uranus and Neptune intersect a temperature-pressure regime in which methane first transforms into a mixture of hydrocarbon polymers8, whereas, in deeper layers, a phase separation into diamond and hydrogen may be possible. Here we show experimental evidence for this phase separation process obtained by in situ X-ray diffraction from polystyrene (C8H8)nsamples dynamically compressed to conditions around 150 GPa and 5,000 K; these conditions resemble the environment around 10,000 km below the surfaces of Neptune and Uranus9. Our findings demonstrate the necessity of high pressures for initiating carbon-hydrogen separation3and imply that diamond precipitation may require pressures about ten times as high as previously indicated by static compression experiments4,8,10. Our results will inform mass-radius relationships of carbon-bearing exoplanets11, provide constraints for their internal layer structure and improve evolutionary models of Uranus and Neptune, in which carbon-hydrogen separation could influence the convective heat transport7.

This study systematically reviewed differences in pain perception between athletes and normally active controls. We screened MEDLINE, Sport-Discus, EMBASE, Web of Science, PsycINFO, PSYNDEX, and the citations of original studies and systematic reviews. All studies on experimentally induced pain that compared pain perception between athletes and normally active controls were eligible. The main outcome measures were pain tolerance and pain threshold. Effects are described as standardized mean differences and were pooled using random-effects models. Fifteen studies including 899 subjects met the inclusion criteria. Twelve of these studies assessed pain tolerance, and 9 studies examined pain threshold. A meta-analysis of these studies revealed that athletes possessed higher pain tolerance compared to normally active controls (effect size calculated as Hedges' g=0.87, 95% confidence interval [CI(95)] 0.53-1.21; P<0.00001), whereas available data on pain threshold were less uniform (Hedges' g=0.69, CI(95) 0.16-1.21; P=0.01). After exclusion of studies with high risk of bias, differences between groups in pain threshold were not significant any longer. Our data suggest that regular physical activity is associated with specific alterations in pain perception. Psychological and biological factors that may be responsible for these alterations are discussed. [ABSTRACT FROM AUTHOR]

The evaluation of real-world data (RWD) enables insights to be gained from a wide range of patient data collected in routine clinical practice. In addition, multicenter analyses represent a broad and representative patient population and have the potential to capture the actual treatment situation. As a basis for this, the definition of datasets and an infrastructure for data exchange is necessary. Data integration centers (DIC) have already been established at (university) hospitals throughout Germany in order to extract RWD for scientific analyses from the various source systems and integrate them into research-compatible data infrastructures. The project described here aims to demonstrate the added value of this data integration using a case of application in ophthalmology, defining a core dataset as an ophthalmology extension module and establishing a cross-site data exchange infrastructure. As a first step, the treatment success of eye diseases treated with intravitreal injection (IVI) should be improved. To achieve this goal a dashboard for clinical data is provided that clearly visualizes the merged data. Furthermore, algorithms will be developed to identify new imaging biomarkers that can be used for treatment monitoring and predict treatment outcomes., Competing Interests: Einhaltung ethischer Richtlinien Interessenkonflikt L. Holtrup, J. Varghese, A.K. Schuster, B. Poschkamp, C. Hampf, D. Waltemath, L. Wahle, M. Lipprandt, D.A. Merle, P. Berens, O. Kohlbacher, V. Kakkassery, M. Bartos, F. Ziemssen, T. Wendt, K. Hoffmann und N. Eter geben an, dass kein Interessenkonflikt besteht.Für diesen Beitrag wurden von den Autor/-innen keine Studien an Menschen oder Tieren durchgeführt. Für die aufgeführten Studien gelten die jeweils dort angegebenen ethischen Richtlinien., (© 2024. The Author(s).)

Aims: Previous work has identified several limitations in "Summaries of Product Characteristics" (SmPCs), which are associated with risks for patients. The aim of this study was to evaluate pharmacists' and physicians' interpretation of contraindications in SmPCs and reasons for their nonadherence in clinical routine., Methods: For 20 commonly missed or ignored absolute contraindications, an anonymous online survey providing 24 clinical example cases (one or two per contraindication) for physicians and pharmacists was developed. Experts in medication safety were asked whether the respective case fulfilled the definition of the contraindication in the SmPC: (a) formally, irrespective of the clinical relevance of the contraindication (17 cases), and (b) whether the contraindication was deemed clinically relevant in each respective case (24 cases)., Results: Twenty-seven pharmacists and 27 physicians completed the survey. For only one case (1/17; 5.8%) did all experts agree on the same answer option regarding the formal fulfilment of a given contraindication statement. Experts gave heterogeneous answers regarding the interpretation of a contraindication. For instance, among 10 predefined answer options for the contraindication "active liver disease" in the SmPC of simvastatin, every option was selected by at least six experts. In 17/24 (70.8%) clinical example cases a majority of experts agreed on the clinical relevance of a given contraindication. Key reasons for nonadherence to contraindications were "patient monitoring possible", "lack of alternative treatment" and "acute/severe situations"., Conclusions: Experts' disagreement on the interpretation of contraindications in SmPCs using clinical example cases indicates that further efforts are needed to improve their usability in clinical routine., (© 2024 The Author(s). British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.)

Aim: The purpose of this study was to assess the prevalence of strabismus and nystagmus and to analyse associated factors in preterm and full-term infants in adulthood., Methods: The Gutenberg Prematurity Eye Study is a retrospective cohort study with a prospective ophthalmological examination of participants born preterm and full-term (aged 18-52 years). Perinatal data were carefully assessed for risk factors and comprehensive ophthalmological examinations were conducted. The association between strabismus and nystagmus was assessed by analysing 16 different perinatal and actual risk factors in multivariable analysis. Participants were grouped into full-term controls (gestational age (GA) at birth ≥37 weeks), preterm participants without retinopathy of prematurity (ROP) and GA 33-36 weeks (group 2), GA 29-32 weeks (group 3), GA ≤28 weeks (group 4), non-treated ROP (group 5) and treated ROP (group 6)., Results: In total, 892 eyes of 450 preterm and full-term individuals (mean age: 28.6 years, SD: ± 8.6 years, 251 females) were included. Strabismus was observed in 2.1% (3/140), 6.6% (9/137), 17.4% (16/92), 11.1% (2/18), 27.1% (13/48) and 60% (9/15) of participants and nystagmus in 0.7% (1/140), 1.5% (2/137), 4.3% (4/92), 5.6% (1/18), 10.4% (5/48) and 26.7% (4/15) of participants in the respective groups. In the multivariable regression model, strabismus was associated with GA (OR=0.90; p=0.046), anisometropia ≥1.5 diopter (OR=3.87; p=0.003), hypermetropia ≥2 diopter (OR=9.89; p<0.001) and astigmatism ≥1.5 diopter (OR=2.73; p=0.017). Esotropia was more frequent than exotropia and hypermetropia/hypometropia. Most strabismus cases occurred within the first 10 years of life. The strongest predictor associated with nystagmus was perinatal adverse events (OR=15.8; p=0.002)., Conclusion: Low GA and refraction of the eye are independent risk factors for strabismus, which typically occurs in the first 10 years of life. Perinatal adverse events are the most important factors for the presence of nystagmus in adulthood., Competing Interests: Competing interests: NP receives financial support and grants from Novartis, Ivantis, Santen, Thea, Boehringer Ingelheim Deutschland GmbH & Co. KG, Alcon and Sanoculis. AKS receives research support from Allergan, Bayer, Heidelberg Engineering, PlusOptix and Novartis., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Psychological resilience is known as a protective factor against mental health disorders for which valid measures are indispensable. The present work aims to evaluate the Resilience Scale-5 (RS-5) psychometrically, and provide norm values., Methods: Data from the Gutenberg Health Study (GHS), encompassing 7,496 participants aged 25 to 86, spanning the years 2017 to 2022, was used. Selectivity, item difficulty, internal consistency, construct and factor validity, as well as factorial invariance were tested. Additionally, correlations and associations with depression, anxiety, and sociodemographic factors were determined. Furthermore, norm values were provided., Results: The RS-5 displayed robust psychometric properties. Participants reported an average resilience score of 28.94 (SD = 5.53, median = 30, IQR = 6, range = 5-35), with those aged ≥75 exhibiting the highest resilience levels (M = 30.21, SD = 5.75, median = 32, IQR = 7). The RS-5 displayed a very good model fit, affirming measurement invariance across sex and age decades. Construct validity found support through anticipated intercorrelations with related psychological constructs. Significant correlations (p < .001) linked higher resilience with female gender, advanced age, higher education, elevated household income, and diminished psychological distress., Conclusion: The RS-5 emerged as a reliable and economic instrument for assessing psychological resilience in individuals aged 25 to 86. The study unraveled distinct sociodemographic characteristics significantly tied to resilience levels within this cohort. In contributing recent norm values tailored to the German population, this research enhances the practical applicability of the RS-5 across diverse contexts and enriches our comprehension of the demographic nuances associated with psychological resilience., Competing Interests: Philipp S. Wild is funded by the Federal Ministry of Education and Research (BMBF 01EO1503). P.S.W. and T.M. are PIs and O.H. is a Young Scientist of the DZHK (German Center for Cardiovascular Research), Partner Site Rhine-Main, Mainz, Germany. There are no patents, products in development, or marketed products to declare. This does not alter the authors’ adherence to all of the journal policies on sharing data and materials. The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The other authors A.C.R., J. G.-K., E.B., K.L., D.G., D.Z., J.C., A.K.S., M.S., K.J.L., J.M.S., W.R., A.D., M.M, and M.E.B. declare no competing interests. This does not alter our adherence to PLOS ONE policies on sharing data and materials., (Copyright: © 2024 Reinwarth et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objective: To distinguish the patterns of inner ear changes between meningogenic and otogenic routes in meningitis cases. Our hypothesis is that pinpointing distinct patterns linked to each route could aid in the development of diagnostic strategies and targeted therapies., Methods: Temporal bones (TBs) from patients with a history of meningitis and histopathological evidence of labyrinthitis were divided into two groups (otogenic and meningogenic). Inner ear histopathological examination was performed to identify qualitative and semi-quantitative changes. This assessment encompassed inflammation patterns, indications of early ossification, hair cell loss, and alterations in the lateral wall, round window membrane, cochlear aqueduct and vestibular aqueduct., Results: Thirty-six TBs were included in the study (otogenic, 21; meningogenic, 15). Generalized labyrinthitis was more common in otogenic cases (100% vs. 53%, p < 0.001). Early signs of cochlear ossification were exclusively observed in otogenic cases (9 TBs). The spiral ligament of otogenic cases has shown a uniform loss of fibrocytes across all cochlear turns, while meningogenic cases showed more severe loss in the apical turn. Otogenic cases exhibited a higher prevalence of severe inflammation of the cochlear aqueduct and endolymphatic sac. Meningogenic cases showed more severe loss of vestibular hair cells in the otolithic organs., Conclusion: Otogenic cases displayed a higher prevalence of changes in the spiral ligament and signs of early ossification, whereas meningogenic cases were associated with a higher degree of vestibular damage. Our findings emphasize the importance of considering the infection route and its implications for timely diagnosis and development of pathology-oriented treatment strategies., Level of Evidence: NA Laryngoscope, 2024., (© 2024 The Author(s). The Laryngoscope published by Wiley Periodicals LLC on behalf of The American Laryngological, Rhinological and Otological Society, Inc.)

Background: Large language models (LLMs) such as ChatGPT-4 and Google Gemini show potential for patient health education, but concerns about their accuracy require careful evaluation. This study evaluates the readability and accuracy of ChatGPT-4 and Google Gemini in answering questions about retinal detachment., Methods: Comparative study analyzing responses from ChatGPT-4 and Google Gemini to 13 retinal detachment questions, categorized by difficulty levels (D1, D2, D3). Masked responses were reviewed by ten vitreoretinal specialists and rated on correctness, errors, thematic accuracy, coherence, and overall quality grading. Analysis included Flesch Readability Ease Score, word and sentence counts., Results: Both Artificial Intelligence tools required college-level understanding for all difficulty levels. Google Gemini was easier to understand (p = 0.03), while ChatGPT-4 provided more correct answers for the more difficult questions (p = 0.0005) with fewer serious errors. ChatGPT-4 scored highest on most challenging questions, showing superior thematic accuracy (p = 0.003). ChatGPT-4 outperformed Google Gemini in 8 of 13 questions, with higher overall quality grades in the easiest (p = 0.03) and hardest levels (p = 0.0002), showing a lower grade as question difficulty increased., Conclusions: ChatGPT-4 and Google Gemini effectively address queries about retinal detachment, offering mostly accurate answers with few critical errors, though patients require higher education for comprehension. The implementation of AI tools may contribute to improving medical care by providing accurate and relevant healthcare information quickly., (© 2024. The Author(s).)

Background: Peripheral hypertrophic subepithelial corneal opacification (PHSCO) is a corneal disease that may severely affect vision. The major goal of this study was to test the hypothesis that tear secretion, medication and systemic diseases are associated with PHSCO., Methods: This is a retrospective, case-control study conducted at the Department of Ophthalmology, University Medical Center of the Johannes Gutenberg University Mainz. We analysed medical records of patients diagnosed with PHSCO. Sex, age, Schirmer's test II, general medication and medical history were assessed and compared to an age- and sex-matched control group from the Gutenberg Health Study (GHS)., Results: One hundred ninety-five eyes of 112 patients with PHSCO were included. Eighty-eight patients were female with a mean age of 55.3 ± 14.7 years (23-89 years) and 24 patients were male with a mean age of 59.3 ± 12.6 years (38-84 years). In 83 patients (74.1%) both eyes were involved. The Schirmer's test II was significantly reduced in patients with PHSCO compared to the GHS control group (p < 0.001). Patients with PHSCO were more frequently administered artificial tears and steroid eye drops (p < 0.001) and were more hyperopic than healthy controls (p = 0.01). Systemic diseases or medication did not differ markedly between PHSCO and healthy controls., Conclusion: Reduced tear secretion and more frequent use of artificial tears in patients with PHSCO suggest a link between PHSCO and dry eye disease. The results of the study do not support our hypothesis that PHSCO is associated with systemic diseases. Interestingly, patients with PHSCO were less frequently on β-blockers than control subjects., (© 2024 The Authors. Acta Ophthalmologica published by John Wiley & Sons Ltd on behalf of Acta Ophthalmologica Scandinavica Foundation.)

Prcis: Bleb revision procedures for hypotony maculopathy (HM) following glaucoma filtering surgery show promising outcomes, including notable improvements in visual acuity and IOP., Purpose: This study assesses morphologic characteristics using SD-OCT in patients with HM following glaucoma filtering surgery and evaluates the results of its treatment., Materials and Methods: A retrospective analysis of all HM patients between January 2019 and March 2023. Inclusion criteria consisted of both preoperative and postrevision SD-OCT images of the macula and the presence of HM as observed on OCT images preoperatively. HM was graded according to its appearance in OCT both prerevision and postrevision surgery. Changes in visual acuity and IOP were assessed., Results: A total of 45 eyes of 45 patients were included. In all, 21 eyes had HM limited to retinal pigment epithelium (RPE), 18 eyes had involvement of RPE and photoreceptor layers, and 6 eyes had additional intraretinal or subretinal edema. After revision surgery with IOP elevation, 64% of eyes had complete HM regression with no HM signs in OCT imaging. Overall, 80% of patients achieved at least 1 grade improvement in HM. Preoperative visual acuity increased from 0.7±0.4 (logMAR) to 0.4±0.4 at 2 weeks postoperatively, over the course of an increase of IOP from 3.5±1.8 to 17.1±10.6 mm Hg at day 1. Eyes with complete HM regression had higher IOP at day 1 compared with those without improvement ( P =0.04). The median time between HM onset and revision was 10.0 days for those with complete regression and 27 days for those without improvement ( P =0.04)., Conclusions: Bleb revision procedures for HM following glaucoma filtering surgery show promising outcomes, including notable improvements in visual acuity and IOP. The timing of revision surgery appears to influence the outcome. In our study, earlier intervention was associated with better results. Even delayed surgeries can lead to an improvement, although complete morphologic restoration may not be achieved in advanced grades of HM., Competing Interests: Disclosure: The authors declare no conflict of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Although the effect of early childhood stress on central nervous pain processing is well known, studies on the association of prematurity and chronic pain are scarce. This study used data from a single-centre retrospective cohort study followed by a prospective clinical examination and pain assessment. The study was based on data from the local birth registry. Newborns born between 1969 and 2002 who had reached adulthood were eligible .. Using a selection algorithm, a study cohort stratified by gestational age (GA) was recruited. Chronic pain conditions were assessed using questionnaire and standardized pain drawings. Data on the pre-, peri- and postnatal clinical course was assessed from medical records. Multivariable logistic regression analyses were conducted to investigate associations between prematurity and chronic pain with adjustment for age, gender, socioeconomic status, and perinatal stress factors. 427 participants born preterm and full-term were included (age 28.5 ± 8.7 years). Chronic pain conditions were similarly common between groups with different levels of prematurity (GA ≥ 37 weeks: 34.5 %, GA33-36 weeks: 37.6 %, GA32-29 weeks: 25.2 %, GA < 29 weeks: 30.4 %, p = 0.20). In multivariable analyses, no association between low GA and the presence of chronic pain was found (OR = 0.99 (CI95 %: 0.94-1.04, p = 0.63); this was also true for a subanalysis of widespread pain. While neither fetal nutritional status nor perinatal stressors were associated with pain, exposure to maternal but not paternal smoking during pregnancy was associated with increased risk to develop pain (OR = 2.77 (CI95 %: 1.31-5.88, p = 0.008) in adults born preterm and full-term. This study suggests that prematurity by itself does not increase the risk of chronic pain later in life, but provides preliminary evidence for maternal smoking during pregnancy as risk factor., Competing Interests: Declaration of competing interest The Gutenberg Prematurity Study was supported by the Ernst und Berta-Grimmke Stiftung, Stufe 1 support of the UM and the Else Kröner-Fresenius-Stiftung. Tesarz J received support by the German Research Foundation (DFG) within the Collaborative Research Center (SFB) 1158 and by the German Federal Ministry of Education and Research (PerPAIN consortium, FKZ:01EC1904A). Schuster AK holds the professorship for ophthalmic healthcare research endowed by “Stiftung Auge” and financed by “Deutsche Ophthalmologische Gesellschaft” and “Berufsverband der Augenärzte Deutschlands e.V.”. Pfeiffer N receives financial support and grants from Novartis, Ivantis, Santen, Thea, Boehringer Ingelheim Deutschland GmbH & Co. KG, Alcon, and Sanoculis. Schuster AK receives research support from Allergan, Bayer, Heidelberg Engineering, PlusOptix and Norvartis. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. The submitted manuscript does not contain information about medical device(s)/drug(s). The authors report no conflict of interest. No benefits in any form have been or will be received from a commercial party directly or indirectly related to the subject of this manuscript. During the preparation of this manuscript, the authors used natural language processing software (ChatGPT, deepl.com, SciteAI). After using this tools, the author(s) reviewed and edited the content as needed and take full responsibility for the content of the publication., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose: To examine potential changes in the foveal avascular zone (FAZ) during adulthood due to prematurity and retinopathy of prematurity (ROP), as assessed by measurements of the FAZ area and circularity., Methods: The Gutenberg Prematurity Eye Study is a retrospective German cohort study with a prospective ophthalmologic examination of adults aged 18 years to 52 years, born either preterm or full-term, using spectral-domain optical coherence tomography angiography. Participants were categorized into groups based on gestational age and postnatal ROP status. The study conducted multivariable linear regression analyses to explore associations with the FAZ., Results: The study cohort comprised 380 right eyes from individuals born both preterm and full-term, with an average age of 28.4 years ± 8.6 years, including 214 women. The FAZ area decreased as gestational age decreased: FAZ was 0.28 mm 2 ± 0.12 mm 2 in the control group, 0.21 ± 0.10 mm 2 at GA 33 weeks to 36 weeks, 0.18 mm 2 ± 0.10 mm 2 at GA 29 weeks to 32 weeks, 0.11 mm 2 ± 0.10 mm 2 at GA ≤28 weeks, 0.11 mm 2 ± 0.10 mm 2 in ROP without treatment, and 0.11 mm 2 ± 0.10 mm 2 in those requiring ROP treatment. In the multivariable analyses, smaller FAZ was independently associated with gestational age ( P < 0.05), increased foveal retinal thickness ( P < 0.05), and foveal hypoplasia ( P < 0.05). Moreover, no association was seen between visual acuity and FAZ., Conclusion: The main perinatal factor associated with a smaller FAZ in this German cohort is preterm birth, while ROP, ROP treatment, or other perinatal factors do not affect FAZ observed in adulthood. A smaller FAZ shape in preterm individuals might be an indicator of foveal hypoplasia.

Prcis: Based on a large administrative database of German claims data, our study provides current estimates of the prevalence and incidence of primary open angle glaucoma (POAG) in Germany and describes selected outcomes for prevalent patients with POAG., Purpose: To estimate the prevalence and incidence of POAG in Germany, to describe the patient population in terms of comorbidity burden, routine care, and overall healthcare resource utilization (HCRU) and associated costs, and to describe treatment patterns over time in patients undergoing relevant laser procedures., Materials and Methods: Based on anonymized German claims data, we carried out a retrospective, noninterventional study covering calendar years 2016-2021., Results: For the adult German population (≥18 y), we estimated a POAG 1-year prevalence of 1.70% and a 1-year incidence of 0.17% in 2018; both increased with age, peaking in 80- to 89-year-olds. Prevalence and incidence were lower in 2020 (1.65% and 0.16%, respectively), the first year of the SARS-CoV-2 pandemic. Most patients solely received topical treatment. Most surgically treated patients underwent laser trabeculoplasty, followed by laser iridotomy, trabeculectomy, and filtration operations with implant. In patients undergoing laser trabeculoplasty, the treatment regimen was nearly unchanged in the second year after, compared with 2 years before the procedure. Multimorbidity was commonly observed; 75.5% of patients had arterial hypertension and 50.0% had disorders of lipoprotein metabolism and other lipidemias, compared with 60.1% and 39.2%, respectively, in an age- and sex-matched control sample., Conclusions: Our study provides insights into epidemiology and routine care of POAG in Germany and HCRU in prevalent patients. There was little change in treatment regimens in patients who underwent laser trabeculoplasty, 2 years after the procedure. Most patients were multimorbid highlighting the need for comprehensive care., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background & Aims: Elevated liver stiffness has been associated with atrial fibrillation (AFib) in the general population. The mechanism underlying this association is unclear., Methods: Participants were recruited from the general population and prospectively enrolled with follow-up for 5 years. The fibrosis-4 (FIB-4) index was used as a surrogate marker for liver fibrosis. Proteomics analysis was performed using the 92-target Olink inflammation panel. Validation was performed using the NAFLD fibrosis score (NFS), aspartate aminotransferase to platelet index (APRI), and repeat confirmation proteomics., Results: A sample of 11,509 participants with a mean age of 54.0 ± 11.1 years, 51.3% women, and a median FIB-4 index of 0.85 (0.65/1.12), was used. The FIB-4 index was predictive for prevalent (FIB-4 index adjusted odds ratio (aOR) per SD: 1.100 with 95% CI 1.011-1.196; p  = 0.026), but not incident AFib (log[FIB-4 index]) adjusted hazard ratio: 1.125 with 95% CI 0.943-1.342, p  = 0.19). Elastic net regularized regression identified CCL20, DNER, and CXCL10 for prevalent AFib, and AXIN1, CXCL10, and Flt3L for the log(FIB-4 index) (per SD) as most important in common regulated proteins. The relationship between the FIB-4 index, the identified proteins, and AFib was relevant and reproduced at the 5-year follow-up for CXCL10 after adjusting for confounders (log[FIB-4 index] per SD - CXCL10 [per SD] adjusted β 0.160 with 95% CI 0.127-0.194, p <0.0001; CXCL10 [per SD] - AFib aOR 1.455 with 95% CI 1.217-1.741, p <0.0001), reproduced using the NFS and APRI, and corresponding to increased serum levels., Conclusions: CXCL10 is linked to liver fibrosis, as determined by the FIB-4 index, and to prevalent AFib., Impact and Implications: How elevated liver stiffness relates to atrial fibrillation in the general population remains to be clarified. We hypothesized that systemic inflammation against a background of liver fibrosis produced from metabolic dysfunction-associated steatotic liver disease (MASLD), is involved in the pathophysiology of atrial fibrillation. Using large-scale targeted proteomics, we found that CXCL10 is related to both liver fibrosis, as defined by the fibrosis-4 index, and to atrial fibrillation. These results can aid evidence-based drug development for patients with atrial fibrillation and MASLD-related liver fibrosis., (© 2024 The Author(s).)

Purpose: To explore differences in the relationship between gestational age (GA) and birth weight (BW) percentile and ocular geometry between males and females., Methods: The Gutenberg Prematurity Eye Study involved a prospective ophthalmic examination of adults, aged 18 to 52 years, who were born preterm or at term, in Germany. The associations between GA and BW percentile on the main outcome measures were evaluated by uni- and multivariable linear regression analyses. The main outcome measures were central corneal thickness, corneal radius, anterior chamber depth, lens thickness, posterior segment length, and central foveal thickness. Potential sex-specific differences and an effect modification by sex were analyzed., Results: This study involved 438 participants (245 females, 193 males) with an average age of 28.6 ± 8.7 years. In female participants, central foveal thickness was negatively associated with a higher GA (B = -2.99; P < 0.001). Similarly, male participants also demonstrated a negative association between central foveal thickness and GA (B = -4.27; P < 0.001). The multivariable model with effect modification revealed that the central foveal thickness was thicker with lower GA. There was an association between the effect modification of GA with sex and central foveal thickness, demonstrating a more pronounced effect of GA on central foveal thickness in male participants (B = 1.29; P = 0.04)., Conclusions: This study identified a sex-specific correlation between lower GA and thicker central foveal thickness, suggesting differences in the developmental trajectory of this biometric parameter concerning GA. A thicker central foveal thickness might affect the visual acuity of individuals born preterm in adulthood, with a more pronounced impact in males and a potential predisposition to age-related diseases later in life. Sex did not influence the association of GA or BW percentile to other ocular geometric parameters.

Objective: The objective of this study was to investigate whether an obesity-related inflammatory protein signature (OIPS) is associated with adverse cardiovascular events., Methods: The Olink Target 96 Inflammation panel was performed in 6662 participants from the population-based Gutenberg Health Study (GHS). The OIPS was selected by a logistic regression model, and its association with cardiovascular outcomes was evaluated by Cox regression analysis. The GHS-derived OIPS was externally validated in the MyoVasc study., Results: The identified OIPS entailed 21 proteins involved in chemokine activity, tumor necrosis factor (TNF) receptor binding, and growth factor receptor binding. The signature revealed a novel positive association of axis inhibition protein 1 with obesity. The OIPS was associated with increased risk of all-cause and cardiac deaths, major adverse cardiovascular events, and incident coronary artery disease, independent of clinical covariates and established risk instruments. A BMI-stratified analysis confirmed the association of OIPS with increased death in those with obesity and overweight and with increased risk for coronary artery disease in those with obesity. The association of OIPS with increased risk of all-cause and cardiac deaths was validated in the MyoVasc cohort., Conclusions: The OIPS showed a significant association with adverse clinical outcomes, particularly in those with overweight and obesity, and represents a promising tool for identifying patients at higher risk for worse cardiovascular outcomes., (© 2024 The Authors. Obesity published by Wiley Periodicals LLC on behalf of The Obesity Society.)

Purpose: The aim of this study is to investigate the distribution of spherical equivalent and axial length in the general population and to analyze the influence of education on spherical equivalent with a focus on ocular biometric parameters., Methods: The Gutenberg Health Study is a population-based cohort study in Mainz, Germany. Participants underwent comprehensive ophthalmologic examinations as part of the 5-year follow-up examination in 2012-2017 including genotyping. The spherical equivalent and axial length distributions were modeled with gaussian mixture models. Regression analysis (on person-individual level) was performed to analyze associations between biometric parameters and educational factors. Mendelian randomization analysis explored the causal effect between spherical equivalent, axial length, and education. Additionally, effect mediation analysis examined the link between spherical equivalent and education., Results: A total of 8532 study participants were included (median age: 57 years, 49% female). The distribution of spherical equivalent and axial length follows a bi-Gaussian function, partially explained by the length of education (i.e., < 11 years education vs. 11-20 years). Mendelian randomization indicated an effect of education on refractive error using a genetic risk score of education as an instrument variable (- 0.35 diopters per SD increase in the instrument, 95% CI, - 0.64-0.05, p = 0.02) and an effect of education on axial length (0.63 mm per SD increase in the instrument, 95% CI, 0.22-1.04, p = 0.003). Spherical equivalent, axial length and anterior chamber depth were associated with length of education in regression analyses. Mediation analysis revealed that the association between spherical equivalent and education is mainly driven (70%) by alteration in axial length., Conclusions: The distribution of axial length and spherical equivalent is represented by subgroups of the population (bi-Gaussian). This distribution can be partially explained by length of education. The impact of education on spherical equivalent is mainly driven by alteration in axial length., (© 2024. The Author(s).)

Purpose: This study explores associations between fetal growth restriction or excessive fetal growth, along with perinatal factors on the optic nerve head morphology in adulthood., Design: Retrospective cohort study., Methods: This retrospective cohort study involved a prospective ophthalmological examination of individuals born at full term (with a gestational age of ≥37 weeks) from 1969 to 2002. Each participant underwent nonmydriatic fundus camera photography to capture images of the optic discs, followed by manual measurements. The vertical cup-to-disc ratio (VCDR) and optic disc area were examined and analyzed in relation to the baby's birth weight relative to the gestational age. These categories included those with former moderate (birth weight percentile between the 3rd and <10th), severe SGA (below the third percentile), normal (AGA, 10th-90th percentile), and moderately (birth weight >90th-97th percentile) and severely (birth weight >97th percentile) large for gestational age (LGA) adults within the age range of 18 to 52 years., Results: Overall, 535 eyes of 280 individuals (age 29.7 ± 9.2 years, 144 females) born at full term were included. Multivariable analysis showed a significant association between a larger VCDR and the severe SGA group (B = 0.05, 95% CI 0.01-0.10; P = .02). In the univariable model, placental insufficiency was associated with VCDR (B = 0.10, 95% CI 0.01-0.19; P = .03). Other perinatal factors did not demonstrate an association with VCDR. Furthermore, there was an indication of an association suggesting a smaller optic disc area in individuals born moderately SGA at full term (B = -0.17, 95% CI -0.33 to -0.001; P = .05)., Conclusions: This study provides evidence that individuals born at-term with severe SGA have an increased VCDR, suggesting that fetal growth restriction has a lasting impact on optic disc morphology independent of prematurity throughout adulthood., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background : The aim of this study was to evaluate the short-term efficacy and safety of the Paul Glaucoma Implant (PGI) in pediatric eyes diagnosed with glaucoma following congenital cataract surgery (GFCS). Methods : A retrospective, single-center, descriptive study was conducted on consecutive children diagnosed with GFCS who underwent PGI implantation between July 2022 and November 2023 at the University Medical Center Mainz. The primary outcome measure was the reduction in IOP at the last follow-up visit. Results : Ten eyes of nine children were included in the study. The mean follow-up time was 7.70 ± 4.22 months (4.68-10.72 months). At the end of the study follow-up, the mean (95% CI) reduction in IOP was -14.8 ± 8.73 mmHg (-8.56 to -21.04 mmHg, p < 0.001). At the last follow-up, 30.0% (3/10) of patients achieved an IOP (intraocular pressure) of ≥6 and ≤21 mmHg with a reduction in IOP of ≥25% without treatment, while 90.0% (9/10) achieved this target IOP regardless of glaucoma medication treatment. The mean number of antiglaucoma medications was significantly reduced from 3.50 (IQR = 1) to 2.0 (IQR = 2, p = 0.01), and the visual acuity logMAR improved from 1.26 ± 0.62 to 1.03 ± 0.48 ( p = 0.04). Only one eye experienced numerical hypotony (4 mmHg) without choroidal detachment or anterior chamber shallowing within the first 24 h. No other adverse events were observed during the follow-up period. Conclusions : PGI implantation significantly lowered IOP and the number of antiglaucoma eye drops with a favorable safety profile in children diagnosed with GFCS, thereby achieving a high rate of qualified surgical success in the short term.

Purpose: The Oldenburg Sentence Test (OLSA) is a German matrix test designed to determine speech recognition thresholds (SRT). It is widely used for hearing-aids and cochlear implant fitting, but an age-adjusted standard is still lacking. In addition, knowing that the ability to concentrate is an important factor in OLSA performance, we hypothesized that OLSA performance would depend on the time of day it was administered. The aim of this study was to propose an age standardization for the OLSA and to determine its diurnal performance., Methods: The Gutenberg Health Study is an ongoing population-based study and designed as a single-centre observational, prospective cohort study. Participants were interviewed about common otologic symptoms and tested with pure-tone audiometry and OLSA. Two groups-subjects with and without hearing loss-were established. The OLSA was performed in two runs. The SRT was evaluated for each participant. Results were characterized by age in 5-year cohorts, gender and speech recognition threshold (SRT). A time stamp with an hourly interval was also implemented., Results: The mean OLSA SRT was - 6.9 ± 1.0 dB (group 1 male) and - 7.1 ± 0.8 dB (group 1 female) showing an inverse relationship with age in the whole cohort, whereas a linear increase was observed in those without hearing loss. OLSA-SRT values increased more in males than in females with increasing age. No statistical significance was found for the diurnal performance., Conclusions: A study with 2900 evaluable Oldenburg Sentence Tests is a novelty and representative for the population of Mainz and its surroundings. We postulate an age- and gender-standardized scale for the evaluation of the OLSA. In fact, with an intergroup standard deviation (of about 1.5 dB) compared to the age dependence of 0.7 dB/10 years, this age normalization should be considered as clinically relevant., (© 2023. The Author(s).)

Background: The pathophysiology of tinnitus is not yet fully understood. Although there is a large amount of evidence associating traffic noise exposure with non-auditory health outcomes, there is no evidence regarding the impact of noise annoyance on auditory disorders such as tinnitus., Objective: Thus, we aimed to investigate the association between noise annoyance due to different sources and tinnitus presence and distress in the general population., Methods: Data of 6813 participants from a large German population-based cohort were used (Gutenberg Health Study). Participants were asked about the presence of tinnitus and how much they were bothered by it. In addition, information on annoyance from road traffic, aircraft, railways, industrial, and neighborhood noise during the day and sleep was collected through validated questionnaires., Results: The prevalence of tinnitus was 27.3%, and the predominant sources of noise annoyance in these subjects were aircraft, neighborhood, and road traffic noise. Overall, logistic regression results demonstrated consistent positive associations between annoyance due to different noise sources and prevalent risk of tinnitus with increases in odds ratios ranging from 4 to 11% after adjustment for sex, age, and socioeconomic status. Likewise, consistent increases in odds ratios were observed for tinnitus distress in subjects with prevalent tinnitus. For instance, neighborhood noise annoyance during the sleep was associated with a 26% increase in tinnitus distress (OR 1.26, 95% CI 1.13; 1.39)., Impact: This is the first study investigating the association between noise annoyance and tinnitus presence and distress in a large cohort of the general population. Our results indicate consistent and positive associations between various sources of noise annoyance and tinnitus. These unprecedented findings are highly relevant as noise annoyance and tinnitus are widespread. The precise etiology and locus of tinnitus remain unknown, but excessive noise exposure is thought to be among the major causes. This study suggests that transportation and neighborhood noise levels thought merely to contribute to annoyance and non-auditory health effects may be sufficient to cause or exacerbate tinnitus., (© 2024. The Author(s).)

Introduction: Epidemiologic data on age-related macular degeneration (AMD) are mainly based on cohort studies, including both diagnosed and undiagnosed cases. Using health claims data allows estimating epidemiological data of diagnosed subjects with AMD within the health care system using diagnosis codes from a regional claims database (AOK PLUS) to estimate the prevalence and incidence of non-exudative and exudative AMD in Germany., Methods: Patients with AMD were identified among AOK PLUS insured patients based on at least two outpatient, ophthalmologic or one inpatient H35.3 diagnoses for the years 2012 to 2021. Patients without continuous observation in a calendar year were excluded. Prevalence was assessed, and 1-year cumulative incidence was determined by the number of newly diagnosed patients divided by the number of individuals at risk. For 2020 and 2021, the AMD stage was assessed by diagnostic subcodes for non-exudative and exudative AMD, respectively. For 2012 to 2019, patient numbers were estimated based on the average proportions of non-exudative AMD and exudative AMD, respectively, in 2020 and 2021. Incidence and prevalence numbers were then extrapolated to Germany., Results: Between 2012 to 2021, the prevalence of diagnosed AMD cases remained relatively stable among approximately 3.27 million AOK PLUS insured persons, ranging from 0.96% (minimum in 2021) to 1.31% (maximum in 2014) for non-exudative AMD, about twice as high as for exudative AMD (min-max: 0.53-0.72%). The age- and sex-adjusted projections amounted to 644,153 diagnosed non-exudative and 367,086 diagnosed German patients with exudative AMDs in 2021. The 1-year cumulative incidence for non-exudative and exudative AMD, respectively, ranged from 122,427-142,932 to 46,092-86,785 newly diagnosed cases., Conclusion: The number of diagnosed cases with AMD in Germany has increased slightly over the past decade. For the first time, patient counts with non-exudative and exudative AMD were approximated for Germany based on a representative, large-scale database study., (© 2024. The Author(s).)

Background : Preterm birth is a risk factor for a variety of detrimental health outcomes. Previous studies have identified recalled (or remembered) parental rearing behaviour as a potential modifier of preterm individuals' mental health in adulthood. However, no investigations to date have contrasted the parents' and children's views, explored whether their congruence is associated with preterm individuals' mental health, or tested associations with maternal self-reported first skin-on-skin contact. Methods : This cohort study involved 199 participants of the Gutenberg Prematurity Eye Study (GPES), with prospective clinical examination and psychological assessment data available for individuals born preterm and term and their mothers' perspective on recalled parental rearing behaviour. Participants also completed the Patient Health Questionnaire-9 (PHQ-9). Results : There were substantial similarities between reported recalled maternal rearing behaviour of individuals born preterm and at term and their mothers, with individuals born preterm with lower gestational age (age of the pregnancy from the woman's last menstrual period) recalling mothers as comparatively more controlling and overprotective. Incongruence in recalled rejection/punishment was associated with more depressive symptoms. Late first skin-to-skin contact was related to more recalled maternal rejection/punishment, less emotional warmth, and more control/overprotection. Conclusions : this study expands the knowledge about the interrelations of preterm birth, maternal rearing behaviour, and mental health, underscoring the relevance of first relationship experiences, including close intimate contact., Competing Interests: N.P. receives financial support and grants from Novartis, Ivantis, Santen, Thea, Boehringer Ingelheim Deutschland GmbH & Co., Ltd., KG, Alcon, and Sanoculis. A.K.S. receives research support from Allergan, Bayer, Heidelberg Engineering, PlusOptix, and Novartis.