100 results on '"Theodoropoulou S"'
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2. Democracy with foresight: the key to a socially sustainable transition in Europe (and beyond)
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Countouris, N., Piasna, A., Theodoropoulou, S., Azmanova, Albena, Nicolaidis, Kalypso, Countouris, N., Piasna, A., Theodoropoulou, S., Azmanova, Albena, and Nicolaidis, Kalypso
- Abstract
How can the European Union steer a course towards long-term social and ecological well-being in a context of incessant emergencies? Two decades of perpetual crisis management have greatly eroded Europe’s capacity to pursue a sustainable future, as considerations of short-term expediency continue to hamper the four transitions that are necessary – green, digital, geopolitical and socio-economic. At the same time, however, few polities in the world are better suited to the design and promotion of long-term policies. This editorial draws on its authors’ respective research into progressive social transformation and sustainable European integration to identify a path for the socially sustainable transition which we now need and which the rest of this issue of Benchmarking Working Europe further explores.
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- 2023
3. Study of Xbal and Pvull polymorphisms of estrogen receptor alpha (ERα) gene in girls with precocious/early puberty
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Theodoropoulou, S. Papadopoulou, A. Karapanou, O. Priftis, K. Papaevangelou, V. Papadimitriou, A.
- Abstract
Purpose: Studies examining association of estrogen receptor alpha (ERα) polymorphisms with early puberty are scarce and results are controversial; data in Caucasian girls are lacking. Main objective was to determine association of Xbal and Pvull polymorphisms of ERα gene in Greek girls with precocious/early puberty Methods: We studied 107 girls with idiopathic precocious/early puberty and 81 young women with pubertal maturation within normal age (controls). Pubertal stage, height SDS (HSDS), and BMI z-score were determined in patients. In controls, height was measured and menarcheal age was self-reported. All participants in the study were genotyped for XbaI and PvuII polymorphisms of the ERα gene. Results: There was no significant difference in XbaI and PvuII polymorphisms between patients and controls. Homozygous, xx and pp, girls had an earlier onset of puberty, although non-significant, than heterozygous or with no polymorphisms p = 0.9; in girls with pubertal onset
- Published
- 2021
4. Structural properties of Ge doped CuGaSe 2 films studied by Raman and Photoluminescence spectroscopy
- Author
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Theodoropoulou, S., Papadimitriou, D., Doka, S., Schedel-Niedrig, Th., and Lux-Steiner, M.Ch.
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- 2007
- Full Text
- View/download PDF
5. Structural and optical characterization of pyrolytic carbon derived from novolac resin
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Theodoropoulou, S., Papadimitriou, D., Zoumpoulakis, L., and Simitzis, J.
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- 2004
- Full Text
- View/download PDF
6. Raman and photoreflectance study of CuIn 1 − x Ga xSe 2 epitaxial layers
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Theodoropoulou, S., Papadimitriou, D., Rega, N., Siebentritt, S., and Lux-Steiner, M.Ch.
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- 2006
- Full Text
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7. Serous macular detachment due to nasally located optic disc pit-coloboma
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Theodoropoulou, S. Theodossiadis, G. Sallam, A. Theodossiadis, P.
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- 2018
8. Spontaneous resolution of vitreomacular traction demonstrated by spectral-domain optical coherence tomography
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Theodossiadis, G.P. Grigoropoulos, V.G. Theodoropoulou, S. Datseris, I. Theodossiadis, P.G.
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genetic structures ,sense organs ,eye diseases - Abstract
Purpose To evaluate the natural course of idiopathic vitreomacular traction (VMT) with spectral-domain optical coherence tomography (SDOCT) from the vitreomacular adhesion (VMA) stage to the spontaneous resolution of VMT. Design Prospective observational case series. Methods We studied the natural course of idiopathic VMT in 46 eyes (46 patients), divided into those that proceeded to spontaneous VMT resolution (12 cases) and those that remained at the VMT stage (34 cases). All patients were examined with SDOCT at regular 3-month intervals. We recorded the vitreomacular angle of VMA nasally and temporally, the horizontal diameter of VMA, macular thickness, visual acuity, photoreceptor layer, and external limiting membrane. Results In the 12 eyes that proceeded to spontaneous resolution, the vitreous adhesion angle had a mean increase of 38 degrees at VMT, compared to the angle at the VMA stage. In the 34 eyes that remained at the VMT stage, the mean angle of traction increased by only 1 degree throughout follow-up. In all 46 patients, the angle at the VMT stage was significantly associated with traction resolution (nasally P =.001, temporally P 400 μm compared with that of eyes with a VMT diameter
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- 2014
9. Photoreceptor layer changes overlying drusen in eyes with age-related macular degeneration associated with vitreomacular traction
- Author
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Theodossiadis, P.G. Theodoropoulou, S. Stamatiou, P. Datseris, I. Theodossiadis, G.P.
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genetic structures ,sense organs ,eye diseases - Abstract
Purpose: To investigate by spectral-domain optical coherence tomography (SD-OCT) changes of photoreceptor layers over drusen in cases of dry type age-related macular degeneration associated with vitreomacular traction (VMT). Methods: Clinical examination, fluorescein angiography, fundus photography, and SD-OCT data were retrospectively studied for a consecutive series of 27 patients with drusen, pseudodrusen, and VMT. Control groups of 32 patients with VMT without drusen and 34 patients with drusen and pseudodrusen without VMT were also studied. Results: The examination revealed disruption of the line corresponding to the inner segment ellipsoid (ISel), previously called inner segment/outer segment junction, of photoreceptor layer, and development of cystoid edema in significantly higher incidence in VMT associated with drusen group. 22 out of 32 eyes with VMT and drusen (68.75%) had disrupted ISel, compared to 8 out of 37 (21.6%) control eyes with drusen only and to 12 out of 37 (32.4%) control eyes with VMT only. Chi-square analysis showed significant association between drusen and pseudodrusen on fovea, VMT, and localization of ISel disruption. The changes of the ISel were mainly found in the area that corresponded to VMT. The SD-OCT revealed drusen throughout the macula and discontinuation of ISel only in the fovea in 4 of 32 (12.5%) eyes with VMT, whereas none of 37 control eyes with drusen only had similar appearance. Conclusions: The drusen in association with the cystoid macular edema induced by vitreous traction contribute to the photoreceptor layer defect overlying drusen in the fovea. In addition, the number of drusen and pseudodrusen was increased in the area of the vitreous traction compared to the peripheral retina. © 2013 Wichtig Editore.
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- 2013
10. Dry eye in Graves' ophthalmopathy: Correlation with corneal hypoesthesia
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Achtsidis, V. Tentolouris, N. Theodoropoulou, S. Panagiotidis, D. Vaikoussis, E. Saldana, M. Gouws, P. Theodossiadis, P.G.
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genetic structures ,sense organs ,eye diseases - Abstract
Purpose: To evaluate dry eye disease and corneal sensitivity in patients with early and active Graves' ophthalmopathy (GO). Methods: A total of 52 eyes of 26 patients with early GO and 74 eyes of 37 age- and sex-matched controls were included in our study. Dry eye disease was assessed based on the criteria of theInternational Dry Eye Workshop. Diagnosis of early GO was based on the European Group on Graves' Orbitopathy consensus statement. Clinical Activity Score (CAS) and Werner-NOSPECS Score were determined. Corneal sensitivity was assessed using a Cochet-Bonnet aesthesiometer. Results: A total of 67.8% of patients with early GO and 13.5% of healthy controls had ocular surface dryness (p
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- 2013
11. The effect of alpha antagonists on pupil dynamics: Implications for the diagnosis of intraoperative floppy iris syndrome
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Theodossiadis, P.G. Achtsidis, V. Theodoropoulou, S. Tentolouris, N. Komninos, C. Fountas, K.N.
- Abstract
Purpose: To assess pupil dynamics quantitatively in relation to the use of α 1-adrenoceptor antagonists, which contribute to the features of intraoperative floppy iris syndrome, using a new, hand-held, digital pupillometer. Design: Prospective case-control study. Methods: We studied 15 and 25 patients administered tamsulosin and alfuzosin, respectively, as well as 25 control patients. Resting pupil diameter and subsequent contraction, latency, constriction velocity, and dilation velocity were recorded using an electronic pupillometer. All pupil measurements were performed before and after pharmacologic dilation. Results: In predilation pupillary measurements, we detected a significant decrease in maximum pupillary diameter by 0.50 ± 0.19 mm (P =.011) and in the mean percentage of diameter reduction after stimulation (5.23 ± 2.42%, P =.035) in the tamsulosin group. Alfuzosin also induced a significant decrease in maximum pupillary diameter (0.49 ± 0.17 mm, P =.005). Constriction velocity was significantly reduced by 0.70 ± 0.20 m/s (P =.001) in the tamsulosin group and by 0.54 ± 0.18 m/s (P =.004) in the alfuzosin group. In terms of postdilation measurements, maximum and minimum pupil diameters were reduced significantly only in the tamsulosin group (by 1.09 ± 0.31 mm [P =.001] and by 0.89 ± 0.36 mm [P =.016], respectively). Conclusions: We describe a reliable, accurate, and rapid method to acquire quantitative pupil measurements and identify the tendency for intraoperative floppy iris syndrome before cataract surgery after the use of alfuzosin and tamsulosin. This investigation also analyzed the similarities and differences induced by the 2 drugs in predilation and postdilation pupil dynamics, demonstrating that tamsulosin is more potent than alfuzosin in inducing intraoperative floppy iris syndrome. © 2012 Elsevier Inc.
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- 2012
12. Hemodialysis-induced alterations in macular thickness measured by optical coherence tomography in diabetic patients with end-stage renal disease
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Theodossiadis, P.G. Theodoropoulou, S. Neamonitou, G. Grigoropoulos, V. Liarakos, V. Triantou, E. Theodossiadis, G.P. Vlahakos, D.V.
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genetic structures ,sense organs ,eye diseases - Abstract
Background/Aims: To evaluate changes in macular thickness measured by optical coherence tomography (OCT) during a hemodialysis (HD) session in diabetic patients with end-stage renal disease. Methods: 72 eyes of 36 diabetic patients with and without macular edema were evaluated before and immediately after an HD session. Average and maximum macular thicknesses in the central disk (6 mm in diameter) and total macular volume were measured. Results: In the eyes with diabetic macular edema, maximum macular thickness within the central disk of 6 mm, and mainly in its peripheral parts, was significantly reduced by 31.18 ± 4.18 μm after HD (p < 0.001). Average macular thickness and total macular volume were also significantly reduced (p = 0.003 and 0.015, respectively). In diabetic eyes without edema, maximum macular thickness decreased significantly by 11.21 ± 1.98 μm after HD (p < 0.001), while average macular thickness and total macular volume decreased slightly (p = 0.034, p = 0.043). Best-corrected visual acuity failed to change. We found a significant association of macular thickness changes with osmolality reduction and the presence of macular edema. Conclusion: HD decreases macular thickness in diabetic patients with macular edema, while there exists a less-pronounced effect in diabetic eyes without edema. Copyright © 2011 S. Karger AG, Basel.
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- 2012
13. The epidemiology of cataract: A study in Greece
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Theodoropoulou, S. Theodossiadis, P. Samoli, E. Vergados, I. Lagiou, P. Tzonou, A.
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eye diseases - Abstract
Purpose: We conducted a case-control study to identify risk factors for cataract in the Mediterranean Greek population. Three hundred and fourteen cases and 314 frequency-matched controls of both genders, aged 45-85, attending the ophthalmology department of a major teaching hospital in Athens, Greece, were included in the study. Methods: Cases were medically diagnosed and classified. Controls were healthy visitors without cataract. A detailed questionnaire, covering demographic, socioeconomic, somatometric, lifestyle and medical history variables, provided data on possible risk factors for cataract. Analyses were conducted through multiple logistic regression. Main outcome measures: Cataract overall and by type: nuclear, cortical and posterior subcapsular (PSC). Results: Statistically significant increased risk for cataract overall was found for current (OR = 1.99, 95%CI: 1.23-3.23) and ex-smokers (OR = 1.64, 95%CI: 1.02-2.70), history of coronary heart disease (OR = 2.25, 95%CI: 1.43-3.55), family history of ophthalmologic diseases (OR = 1.51, 95%CI: 1.03-2.20) and higher sunlight exposure at the beach (OR = 2.26, 95%CI: 1.37-3.72) as well as at work (OR = 2.03, 95%CI: 1.32-3.12). Use of measures protecting against sunlight at the beach, i.e. hat (OR = 0.58, 95%CI: 0.39-0.85) and vision repair spectacles (OR = 0.44, 95%CI: 0.30-0.65), were associated with reduced risk. Results for cataract overall were also evident for the nuclear type and in most circumstances for PSC type, but were only suggestive for the cortical type of cataract. Conclusion: We identified certain possible risk factors for age-related cataract. In a Mediterranean Greek population, we found that smoking, use of cortisone drops, cardiovascular heart disease and sunlight exposure increase the risk for cataract, while use of hat and vision repair spectacles act protectively. © 2010 The Authors Journal compilation © 2010 Acta Ophthalmol.
- Published
- 2011
14. Interleukin 33/ST2 signaling regulates inflammatory response in choroidal stroma and ocular angiogenesis: implications for age-related macular degeneration
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Theodoropoulou, S., primary, Doyle, S., additional, Copland, D., additional, Liu, J., additional, Wu, J., additional, Campbell, M., additional, and Dick, A., additional
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- 2015
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15. Chronic coffee consumption has an unfavorable effect on aortic stiffness and wave reflections
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Vlachopoulos, C Ioakeimidis, N Dima, I Panagiotakos, D and Theodoropoulou, S Velitzelou, K Stefanadis, C
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- 2005
16. Remission rates with venlafaxine extended release in Greek outpatients with generalized anxiety disorder. A double-blind, randomized, placebo controlled study
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Zissis Np, Theodoropoulou S, I. Nimatoudis, A. Vidalis, J. Kogeorgos, and G. Kaprinis
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Adult ,Male ,Generalized anxiety disorder ,Randomization ,Time Factors ,Placebo-controlled study ,Venlafaxine ,Placebo ,Double-Blind Method ,Recurrence ,Outpatients ,medicine ,Humans ,Pharmacology (medical) ,Psychiatric Status Rating Scales ,Dose-Response Relationship, Drug ,Greece ,Remission Induction ,Venlafaxine Hydrochloride ,medicine.disease ,Cyclohexanols ,Anxiety Disorders ,Psychiatry and Mental health ,Treatment Outcome ,Tolerability ,Anti-Anxiety Agents ,Anesthesia ,Delayed-Action Preparations ,Ambulatory ,Female ,Psychology ,Anxiety disorder ,medicine.drug - Abstract
The primary endpoints in this study were the remission rates [final Hamilton Rating Scale for Anxiety (HAM-A) total score ≤ 7] and reduction from baseline in the HAM-A total score in patients with generalized anxiety disorder (GAD) and no associated depression. Patients with GAD (DSM-IV and HAM-A total score >18) were randomly assigned to treatment with venlafaxine XR or placebo for 8 weeks. A 1-week placebo run-in period preceded the double-blind phase. Patients with a >20% drop in their total HAM-A score during the run-in period, were excluded from the double-blind phase. All patients started therapy with 75 mg/day venlafaxine XR or matched placebo. Patients with less than 30% decrease in their HAM-A total score at the end of the second week, doubled their dose. Patients on the 150 mg/day dose underwent a 1 -week taper period. Of the 24 patients in the venlafaxine XR group, 62.5% achieved remission versus 9.1% in the placebo group (P=0.0006). The mean decrease from baseline in HAM-A total score was 19.2 points for the venlafaxine XR group and 10.8 points for the placebo group (P
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- 2004
17. Attentional facilitation of response is impaired for antisaccades but not for saccades in patients with schizophrenia: Implications for cortical dysfunction
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Smyrnis, N. Malogiannis, I.A. Evdokimidis, I. Stefanis, N.C. Theleritis, C. Vaidakis, A. Theodoropoulou, S. Stefanis, C.N.
- Abstract
The facilitation of response known as the "gap effect" (a decrease of response latency), observed for saccades and antisaccades when attention is modulated prior to such eye movements, was studied in patients with schizophrenia and in controls. The hypothesis tested was whether patients would show a deficient attentional facilitation in response latency. Fifteen patients with schizophrenia and 17 healthy controls performed blocks of saccades and antisaccades in a "gap" condition and an "overlap" condition. Saccade and antisaccade response latencies as well as the error rate for antisaccades were measured for each subject. A similar gap effect (decrease in latency for the gap compared to the overlap condition) was present in the saccade task for patients and controls. In contrast the gap effect in the antisaccade task was absent in 50% of patients compared to none of the controls. This finding was interpreted as indicative of deficient pre-processing in antisaccade-specific cortical areas in schizophrenia (such as the prefrontal cortex), while visually guided saccade processing remained intact. Our results, in addition to many other recent findings, could lead to specific hypotheses on cortical dysfunction in schizophrenia. © Springer-Verlag 2004.
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- 2004
18. Cytokine serum levels, autologous mixed lymphocyte reaction and surface marker analysis in never medicated and chronically medicated schizophrenic patients
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Theodoropoulou, S Spanakos, G Baxevanis, CN Economou, M and Gritzapis, AD Papamichail, MP Stefanis, CN
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A number of immunological parameters were studied in 82 DSM-III-R diagnosed schizophrenic patients (53 first drug-naive and 29 medicated chronic patients) as well as 67 healthy blood donors. The serum levels of interleukin-2 (IL-2), interleukin-1 beta (IL-1 beta) and tumour necrosis factor-alpha (TNF-alpha) were measured and correlated with cellular immunity, as assessed by the autologous mixed lymphocyte reaction (AMLR). T lymphocyte subsets were also examined. The above immune parameters were reassessed in a subgroup of ii first-episode, drug-naive patients 1 month after neuroleptic medication. IL-2 serum levels were significantly lower, and IL-1 beta and TNF-alpha were significantly higher in schizophrenic patients compared with healthy donors (P
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- 2001
19. Ultra-wide field imaging of retinopathy of prematurity (ROP) using Optomap-200TX
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Theodoropoulou, S., primary, Ainsworth, S., additional, and Blaikie, A., additional
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- 2013
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20. Success rates of endoscopic-assisted probing for congenital nasolacrimal duct obstruction in children
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Theodoropoulou, S, primary, Sutherland, M S M, additional, Haddow, K, additional, and Blaikie, A, additional
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- 2013
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21. P-260 Exposure to pesticides is a major risk factor for myelodysplastic syndromes (MDS) in Southwestern Greece
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Avgerinou, C., primary, Kouraklis, A., additional, Theodoropoulou, S., additional, Giannezi, I., additional, Lazaris, V., additional, Lampropoulou, P., additional, Labropoulou, V., additional, Tzouvara, E., additional, Zikos, P., additional, Alamanos, Y., additional, Karakantza, M., additional, and Symeonidis, A., additional
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- 2013
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22. Atypical toxoplasmic retinochoroiditis
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Theodoropoulou, S., primary, Schmoll, C., additional, Templeton, K., additional, and Dhillon, B., additional
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- 2012
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23. Influence of harvest time and after-ripening on the seed quality of eggplant
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Passam, H.C., primary, Theodoropoulou, S., additional, Karanissa, T., additional, and Karapanos, I.C., additional
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- 2010
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24. Optical properties of CuIn1−xGaxSe2quaternary alloys for solar-energy conversion
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Theodoropoulou, S, primary, Papadimitriou, D, additional, Anestou, K, additional, Cobet, Ch, additional, and Esser, N, additional
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- 2008
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25. Band-gap energies and strain effects in CuIn1−xGaxS2based solar cells
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Theodoropoulou, S, primary, Papadimitriou, D, additional, Mamalis, A G, additional, Manolakos, D E, additional, Klenk, R, additional, and Lux-Steiner, M-Ch, additional
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- 2007
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26. Structural properties of Ge doped CuGaSe2 films studied by Raman and Photoluminescence spectroscopy
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Theodoropoulou, S., primary, Papadimitriou, D., additional, Doka, S., additional, Schedel-Niedrig, Th., additional, and Lux-Steiner, M.Ch., additional
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- 2007
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27. Raman and photoreflectance study of CuIn1−xGaxSe2 epitaxial layers
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Theodoropoulou, S., primary, Papadimitriou, D., additional, Rega, N., additional, Siebentritt, S., additional, and Lux-Steiner, M.Ch., additional
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- 2006
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28. Chronic coffee consumption has an unfavorable effect on aortic stiffness and wave reflections
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VLACHOPOULOS, C, primary, IOAKEIMIDIS, N, additional, DIMA, I, additional, PANAGIOTAKOS, D, additional, THEODOROPOULOU, S, additional, VELITZELOU, K, additional, and STEFANADIS, C, additional
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- 2005
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29. Remission rates with venlafaxine extended release in Greek outpatients with generalized anxiety disorder. A double-blind, randomized, placebo controlled study
- Author
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Nimatoudis, I., primary, Zissis, N. P., additional, Kogeorgos, J., additional, Theodoropoulou, S., additional, Vidalis, A., additional, and Kaprinis, G., additional
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- 2004
- Full Text
- View/download PDF
30. Optical properties of carbon materials formed by pyrolysis of novolac-resin/biomass composites
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Theodoropoulou, S., primary, Papadimitriou, D., additional, Zoumpoulakis, L., additional, and Simitzis, J., additional
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- 2004
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31. P.6.040 Is the Brugada electrocardiogram associated with antipsychotic and antidepressant treatment?
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Kounas, S., primary, Rouvali, O., additional, Dalli, P., additional, Efremidis, M., additional, Theodoropoulou, S., additional, and Kardaras, F., additional
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- 2003
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32. Structural properties of Ge doped CuGaSe2 films studied by Raman and Photoluminescence spectroscopy
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Theodoropoulou, S., Papadimitriou, D., Doka, S., Schedel-Niedrig, Th., and Lux-Steiner, M.Ch.
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SPECTRUM analysis , *DIRECT energy conversion , *SOLAR cells , *PROPERTIES of matter - Abstract
Abstract: The structural properties of Ge doped polycrystalline CuGaSe2 films with potential applications in solar cell device technology have been studied by Raman spectroscopy at 300 K and by Photoluminescence (PL) spectroscopy at 300 K and 2 K. The films were intentionally doped with max. 200 keV Ge ions using one- and three-stage ion implantation processes. The Raman spectra of as grown films are dominated by the A1-mode (breathing mode) of the CuGaSe2 absorber at 184 cm−1. It was found, that in doped films the Raman mode intensities are reduced and the B2-modes (TO at 249 cm−1 and LO at 273 cm−1) take over. This implies an increase in structural disorder induced, probably, by bond reorientation effects that favor excitation of asymmetric lattice vibrations (B2) instead of the symmetric ones (A1). Moreover, it was found, that the Raman bands of doped films exhibit asymmetric broadening representative of a Fano line-shape. Changes were more pronounced in films doped at one-stage. The PL-emission of films subjected to one-stage process was enhanced, which supports an increase in structural disorder particularly for these films. On the contrary, for films doped in three-stages, the PL bands are less intensive and the Raman bands are less broadened. [Copyright &y& Elsevier]
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- 2007
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33. Raman and photoreflectance study of CuIn1−xGaxSe2 epitaxial layers
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Theodoropoulou, S., Papadimitriou, D., Rega, N., Siebentritt, S., and Lux-Steiner, M.Ch.
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- *
SPECTRUM analysis , *RAMAN spectroscopy , *LASER beams , *PHOTOVOLTAIC cells - Abstract
Abstract: The structural and optical properties of CuIn1−xGaxSe2 epitaxial layers were studied in dependence of composition by Photoreflectance (PR) spectroscopy at room and low temperatures and by Raman spectroscopy at room temperature. For compositions with [Ga]/([In]+[Ga]) varying between 0.08 and 0.82, the band gap, determined by fitting the PR-spectra with a third derivative functional form, shows a quadratic dependence on composition. The Raman spectra, recorded under excitation with a vertically polarized Kr+-laser beam operated at the 647.1 nm line in the region 50–700 cm−1, consist mainly of peaks assigned to the A1- and B2-phonon modes. The A1-mode dominates the spectra and shifts linearly, with the increase of the [Ga]/([In]+[Ga]) content, from 172 cm−1 (A1-mode frequency of CuInSe2) to 181 cm−1 (A1-mode frequency of CuGaSe2). Combining the Raman and PR-data, an analytical expression has been derived which correlates the band gap energy with the A1 Raman mode frequency for a given composition of the quaternary compound. [Copyright &y& Elsevier]
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- 2006
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34. Interleukin 33/ ST2 signaling regulates inflammatory response in choroidal stroma and ocular angiogenesis: implications for age-related macular degeneration.
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Theodoropoulou, S., Doyle, S., Copland, D., Liu, J., Wu, J., Campbell, M., and Dick, A.
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- *
RETINAL degeneration , *BLINDNESS , *INTERLEUKIN-33 - Abstract
Purpose Age-related macular degeneration (AMD) is a leading cause of irreversible blindness. We wished to elaborate mechanisms that regulate RPE-choroidal microenvironment in AMD. We hypothesize that retinal pigment epithelial cells (RPE) produce interleukin 33 (IL-33) and regulate choroidal stromal fibroblasts and mast cell activation and angiogenesis in an ST2-dependent manner. Through such mechanisms, change in choroidal architecture may contribute to AMD phenotypes observed clinically. Methods Upon treatment, RPE cells, human choroidal fibroblasts and bone-marrow-derived mast cells (BMMC) were assayed by RT- PCR, Western Blot and ELISA. Choroidal sprouting assay and laser-induced choroidal neovascularization (CNV) were used as models of ocular angiogenesis. Results TLR-stimulation of RPE significantly up-regulated IL-33 expression. ST2+ BMMC generated a spectrum of inflammatory cytokines when cultured with IL-33 rich RPE supernatant. Pretreatment with IL-33 antagonist markedly inhibited the ability of BMMC to produce inflammatory mediators. Importantly, activation of inflammatory cascade upon RPE supernatant treatment was abrogated in ST2-/- BMMC. In a wound-healing assay, recombinant IL-33 treatment of human choroidal fibroblasts impaired their ability to migrate and contract collagen gel. Furthermore, IL-33 treatment promoted vascular choroidal sprouting in WT and IL33-/- explants. CNV was also regulated by exogenous and endogenous IL-33 in WT and IL33-/- mice respectively. Conclusions Our data illuminate an endogenous IL-33/ ST2 pathway between RPE function and choroidal stroma, influencing tissue remodeling and regulating angiogenesis. Our findings support IL-33/ ST2 axis as a therapeutic target in AMD. [ABSTRACT FROM AUTHOR]
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- 2015
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35. The effect of alpha antagonists on pupil dynamics: implications for the diagnosis of intraoperative floppy iris syndrome.
- Author
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Theodossiadis PG, Achtsidis V, Theodoropoulou S, Tentolouris N, Komninos C, and Fountas KN
- Published
- 2012
36. Anti-VEGF Therapy to Treat Corneal Neovascularization.
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Papathanassiou, M., Theodoropoulou, S., Analitis, S., and Tzonou, A.
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VASCULAR endothelial growth factors , *NEOVASCULARIZATION - Abstract
The article discusses the role of anti-vascular endothelial growth factor (VEGF) therapy in treatment of corneal neovascularization.
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- 2013
37. Replenishing IRAK-M expression in retinal pigment epithelium attenuates outer retinal degeneration.
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Liu J, Copland DA, Clare AJ, Gorski M, Richards BT, Scott L, Theodoropoulou S, Greferath U, Cox K, Shi G, Bell OH, Ou K, Powell JLB, Wu J, Robles LM, Li Y, Nicholson LB, Coffey PJ, Fletcher EL, Guymer R, Radeke MJ, Heid IM, Hageman GS, Chan YK, and Dick AD
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- Animals, Humans, Male, Mice, Cellular Senescence, Macular Degeneration metabolism, Macular Degeneration pathology, Macular Degeneration genetics, Mice, Inbred C57BL, Mitochondria metabolism, Interleukin-1 Receptor-Associated Kinases metabolism, Interleukin-1 Receptor-Associated Kinases genetics, Mice, Knockout, Oxidative Stress, Retinal Degeneration metabolism, Retinal Degeneration pathology, Retinal Degeneration genetics, Retinal Pigment Epithelium metabolism, Retinal Pigment Epithelium pathology
- Abstract
Chronic inflammation is a constitutive component of many age-related diseases, including age-related macular degeneration (AMD). Here, we identified interleukin-1 receptor-associated kinase M (IRAK-M) as a key immunoregulator in retinal pigment epithelium (RPE) that declines during the aging process. Rare genetic variants of IRAK3 , which encodes IRAK-M, were associated with an increased likelihood of developing AMD. In human samples and mouse models, IRAK-M abundance in the RPE declined with advancing age or exposure to oxidative stress and was further reduced in AMD. Irak3 -knockout mice exhibited an increased incidence of outer retinal degeneration at earlier ages, which was further exacerbated by oxidative stressors. The absence of IRAK-M led to a disruption in RPE cell homeostasis, characterized by compromised mitochondrial function, cellular senescence, and aberrant cytokine production. IRAK-M overexpression protected RPE cells against oxidative or immune stressors. Subretinal delivery of adeno-associated virus (AAV)-expressing human IRAK3 rescued light-induced outer retinal degeneration in wild-type mice and attenuated age-related spontaneous retinal degeneration in Irak3 -knockout mice. Our data show that replenishment of IRAK-M in the RPE may redress dysregulated pro-inflammatory processes in AMD, suggesting a potential treatment for retinal degeneration.
- Published
- 2024
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38. Hybrid Nanoparticles from Random Polyelectrolytes and Carbon Dots.
- Author
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Theodoropoulou S, Vardaxi A, Kagkoura A, Tagmatarchis N, and Pispas S
- Abstract
The present study concerns the preparation of hybrid nanostructures composed of carbon dots (CDs) synthesized in our lab and a double-hydrophilic poly(2-dimethylaminoethyl methacrylate- co -oligo(ethylene glycol) methyl ether methacrylate) (P(DMAEMA- co -OEGMA)) random co polymer through electrostatic interactions between the negatively charged CDs and the positively charged DMAEMA segments of the co polymer. The synthesis of P(DMAEMA- co -OEGMA) co polymer was conducted through RAFT polymerization. Furthermore, the co polymer was converted into a strong cationic random polyelectrolyte through quaternization of the amine groups of DMAEMA segments with methyl iodide (CH
3 I), and it was subsequently utilized for the complexation with the carbon dots. The molecular, physicochemical, and photophysical characterization of the aqueous solution of the co polymers and their hybrid nanoparticles was conducted using dynamic and electrophoretic light scattering (DLS, ELS) and spectroscopic techniques, such as UV-Vis, fluorescence (FS), and FT-IR spectroscopy. In addition, studies of their aqueous solution using DLS and ELS showed their responsiveness to external stimuli (pH, temperature, ionic strength). Finally, the interaction of selected hybrid nanoparticles with iron (III) ions was confirmed through FS spectroscopy, demonstrating their potential application for heavy metal ions sensing.- Published
- 2024
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39. Disengagement and loss to follow-up in intravitreal injection clinics for neovascular age-related macular degeneration.
- Author
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Jones R, Stratton IM, Scanlon PH, and Theodoropoulou S
- Subjects
- Humans, Angiogenesis Inhibitors therapeutic use, Vascular Endothelial Growth Factor A, Follow-Up Studies, Intravitreal Injections, Visual Acuity, Retrospective Studies, Ranibizumab, Wet Macular Degeneration drug therapy
- Abstract
Background/objectives: Timely assessment and treatment of patients with neovascular AMD (nAMD) are crucial to preservation of vision. Loss to follow up (LTFU) in these patients is a problem but this has not been systematically investigated., Subjects/methods: A retrospective review of electronic medical records of patients with nAMD first treated with anti-VEGF therapy from 1st Jan 2014 to 31st Dec 2018, was conducted in January 2021. Any patient not seen for more than 12 months was classed as no longer attending., Results: Of the 1328 patients who attended between 2014 and 2018, 348 had failed to attend and were eligible for inclusion in this study. Reasons noted for discontinuation of care: discharged by clinician (33.3%), died (20.7%), moved to another unit outside of area (17.5%), stopped attending due to ill-health (13.5%), discharged due to failure to attend (5.6%) and patient choice to no longer attend (4.6%). There were 16 (4.6%) who did not receive any further appointments despite clinician request for follow-up. After 5 years, 50.5% of patients were no longer attending for treatment. Age was a factor in failure to attend, with 7 out of 12 patients aged >100 years no longer being followed up, compared to 1 out of 11 of 50-59 year-olds., Conclusions: When analysing visual outcomes in an AMD service it is important to characterise the patients who are lost to follow up. The outcomes for this group may be avoidably poor and understanding the factors influencing LTFU rate is crucial to addressing shortcomings in a hospital AMD service., (© 2023. The Author(s).)
- Published
- 2023
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40. Correction to: Disengagement and loss to follow-up in intravitreal injection clinics for neovascular age-related macular degeneration.
- Author
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Jones R, Stratton IM, Scanlon PH, and Theodoropoulou S
- Published
- 2023
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- View/download PDF
41. Replenishing Age-Related Decline of IRAK-M Expression in Retinal Pigment Epithelium Attenuates Outer Retinal Degeneration.
- Author
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Liu J, Copland DA, Clare AJ, Gorski M, Richards BT, Scott L, Theodoropoulou S, Greferath U, Cox K, Bell OH, Ou K, Powell JLB, Wu J, Robles LM, Li Y, Nicholson LB, Coffey PJ, Fletcher EL, Guymer R, Radeke MJ, Heid IM, Hageman GS, Chan YK, and Dick AD
- Abstract
Unchecked, chronic inflammation is a constitutive component of age-related diseases, including age-related macular degeneration (AMD). Here we identified interleukin-1 receptor-associated kinase (IRAK)-M as a key immunoregulator in retinal pigment epithelium (RPE) that declines with age. Rare genetic variants of IRAK-M increased the likelihood of AMD. IRAK-M expression in RPE declined with age or oxidative stress and was further reduced in AMD. IRAK-M-deficient mice exhibited increased incidence of outer retinal degeneration at earlier ages, which was further exacerbated by oxidative stressors. The absence of IRAK-M disrupted RPE cell homeostasis, including compromised mitochondrial function, cellular senescence, and aberrant cytokine production. IRAK-M overexpression protected RPE cells against oxidative or immune stressors. Subretinal delivery of AAV-expressing IRAK-M rescued light-induced outer retinal degeneration in wild-type mice and attenuated age-related spontaneous retinal degeneration in IRAK-M-deficient mice. Our data support that replenishment of IRAK-M expression may redress dysregulated pro-inflammatory processes in AMD, thereby treating degeneration., Competing Interests: Competing interests ADD, JL and YKC are named inventors on an International Patent Application No: PCT/EP2022/082518. ADD is consultant for Hubble Tx, Affibody, 4 DMT, Novartis, Roche, UCB, Amilera, Janssen, and ActivBio. RG is consultant for Roche, Genentech, Apellis, Novartis, and Bayer.
- Published
- 2023
- Full Text
- View/download PDF
42. Developing decision support tools incorporating personalised predictions of likely visual benefit versus harm for cataract surgery: research programme
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Sparrow JM, Grzeda M, Frost A, Liu C, Johnston RL, Scanlon P, Pithara C, Elliott D, Donovan J, Joseph-Williams N, Holland-Hart D, Donachie PHJ, Dixon P, Kandiyali R, Taylor H, Breheny K, Sterne J, Hollingworth W, Evans D, Fox F, Theodoropoulou S, Hughes R, Quinn M, Gray D, Benjamin L, Loose A, Edwards L, Craggs P, Paget F, Kapoor K, and Searle J
- Abstract
Background: Surgery for established cataract is highly cost-effective and uncontroversial, yet uncertainty remains for individuals about when to proceed and when to delay surgery during the earlier stages of cataract., Objective: We aimed to improve decision-making for cataract surgery through the development of evidence-based clinical tools that provide general information and personalised risk/benefit information., Design: We used a mixed methodology consisting of four work packages. Work package 1 involved the development and psychometric validation of a brief, patient self-reported measure of visual difficulty from cataract and its relief from surgery, named Cataract Patient-Reported Outcome Measure, five items (Cat-PROM5). Work package 2 involved the review and refinement of risk models for adverse surgical events (posterior capsule rupture and visual acuity loss related to cataract surgery). Work package 3 involved the development of prediction models for the Cat-PROM5-based self-reported outcomes from a cohort study of 1500 patients; assessment of the validity of preference-based health economic indices for cataract surgery and the calibration of these to Cat-PROM5; assessment of patients’ and health-care professionals’ views on risk–benefit presentation formats, the perceived usefulness of Cat-PROM5, the value of personalised risk–benefit information, high-value information items and shared decision-making; development of cataract decision aid frequently asked questions, incorporation of personalised estimates of risks and benefits; and development of a cataract decision quality measure to assess the quality of decision-making. Work package 4 involved a mixed-methods feasibility study for a fully powered randomised controlled trial of the use of the cataract decision aid and a qualitative study of discordant or mismatching perceptions of outcome between patients and health-care professionals., Setting: Four English NHS recruitment centres were involved: Bristol (lead centre), Brighton, Gloucestershire and Torbay. Multicentre NHS cataract surgery data were obtained from the National Ophthalmology Database., Participants: Work package 1 – participants ( n = 822) were from all four centres. Work package 2 – electronic medical record data were taken from the National Ophthalmology Database (final set > 1M operations). Work package 3 – cohort study participants were from Bristol ( n = 1200) and Gloucestershire ( n = 300); qualitative and development work was undertaken with patients and health-care professionals from all four centres. Work package 4 – Bristol, Brighton and Torbay participated in the recruitment of patients ( n = 42) for the feasibility trial and recruitment of health-care professionals for the qualitative elements., Interventions: For the feasibility trial, the intervention was the use of the cataract decision aid, incorporating frequently asked questions and personalised estimations of both adverse outcomes and self-reported benefit., Main Outcome Measures: There was a range of quantitative and qualitative outcome measures: questionnaire psychometric performance metrics, risk indicators of adverse surgical events and visual outcome, predictors of self-reported outcome following cataract surgery, patient and health-care practitioner views, health economic calibration measures and randomised controlled trial feasibility measures., Data Sources: The data sources were patient self-reported questionnaire responses, study clinical data collection forms, recorded interviews with patients and health-care professionals, and anonymised National Ophthalmology Database data., Results: Work package 1 – Cat-PROM5 was developed and validated with excellent to good psychometric properties (Rasch reliability 0.9, intraclass correlation repeatability 0.9, unidimensionality with residual eigenvalues ≤ 1.5) and excellent responsiveness to surgical intervention (Cohen delta –1.45). Work package 2 – earlier risk models for posterior capsule rupture and visual acuity loss were broadly affirmed ( C -statistic for posterior capsule rupture 0.64; visual acuity loss 0.71). Work package 3 – the Cat-PROM5-based self-reported outcome regression models were derived based on 1181 participants with complete data ( R
2 ≈ 30% for each). Of the four preference-based health economic indices assessed, two demonstrated reasonable performance. Cat-PROM5 was successfully calibrated to health economic indices; adjusted limited dependent variable mixture models offered good to excellent fit (root-mean-square error 0.10–0.16). The personalised quantitative risk information was generally perceived as beneficial. A cataract decision aid and cataract decision quality measure were successfully developed based on the views of patients and health-care professionals. Work package 4 – data completeness was good for the feasibility study primary and secondary variables both before and after intervention/surgery (data completeness range 100–88%). Considering ability to recruit, the sample size required, instrumentation and availability of necessary health economic data, a fully powered randomised controlled trial (patients, n = 800, effect size 0.2 standard deviations, power 80%; p = 0.05) of the cataract decision aid would be feasible following psychometric refinement of the primary outcome (the cataract decision quality measure). The cataract decision aid was generally well-received by patients and health-care professionals, with cautions raised regarding perceived time and workload barriers. Discordant outcomes mostly related to patient dissatisfaction, with no clinical problem found., Limitations: The National Ophthalmology Database data are expected to include some errors (mitigated by large multicentre data aggregations). The feasibility randomised controlled trial primary outcome (the cataract decision quality measure) displayed psychometric imperfections requiring refinement. The clinical occurrence of discordant outcomes is uncommon and the study team experienced difficulty identifying patients in this situation., Future Work: Future work could include regular review of the risk models for adverse outcomes to ensure currency, and the technical precision of complex-numbers analysis of refractive outcome to invite opportunities to improve post-operative spectacle-free vision. In addition, a fully powered randomised controlled trial of the cataract decision aid would be feasible, following psychometric refinement of the primary outcome (the cataract decision quality measure); this would clarify its potential role in routine service delivery., Conclusions: In this research programme, evidence-based clinical tools have been successfully developed to improve pre-operative decision-making in cataract surgery. These include a psychometrically robust, patient-reported outcome measure (Cat-PROM5); prediction models for patient self-reported outcomes using Cat-PROM5; prediction models for clinically adverse surgical events and adverse visual acuity outcomes; and a cataract decision aid with relevant general information and personalised risk/benefit predictions. In addition, the successful mapping of Cat-PROM5 to existing health economic indices was achieved and the performances of indices were assessed in patients undergoing cataract surgery. A future full-powered randomised controlled trial of the cataract decision aid would be feasible (patients, n = 800, effect size 0.2 standard deviations, power 80%; p = 0.05)., Trial Registration: This trial is registered as ISRCTN11309852., Funding: This project was funded by the National Institute for Health and Care Research (NIHR) Programme Grants for Applied Research programme and will be published in full in Programme Grants for Applied Research ; Vol. 10, No. 9. See the NIHR Journals Library website for further project information., (Copyright © 2022 Sparrow et al. This work was produced by Sparrow et al. under the terms of a commissioning contract issued by the Secretary of State for Health and Social Care. This is an Open Access publication distributed under the terms of the Creative Commons Attribution CC BY 4.0 licence, which permits unrestricted use, distribution, reproduction and adaption in any medium and for any purpose provided that it is properly attributed. See: https://creativecommons.org/licenses/by/4.0/. For attribution the title, original author(s), the publication source – NIHR Journals Library, and the DOI of the publication must be cited.)- Published
- 2022
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43. Unravelling the therapeutic potential of IL-33 for atrophic AMD.
- Author
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Clare AJ, Liu J, Copland DA, Theodoropoulou S, and Dick AD
- Subjects
- Aged, Angiogenesis Inhibitors, Cytokines metabolism, Humans, Interleukin-33 metabolism, Retinal Pigment Epithelium pathology, Vascular Endothelial Growth Factor A metabolism, Visual Acuity, Geographic Atrophy pathology, Wet Macular Degeneration drug therapy, Wet Macular Degeneration metabolism
- Abstract
Age-related macular degeneration (AMD), a degenerative disease affecting the retinal pigment epithelium (RPE) and photoreceptors in the macula, is the leading cause of central blindness in the elderly. AMD progresses to advanced stages of the disease, atrophic AMD (aAMD), or in 15% of cases "wet" or neovascular AMD (nAMD), associated with substantial vision loss. Whilst there has been advancement in therapies treating nAMD, to date, there are no licenced effective treatments for the 85% affected by aAMD, with disease managed by changes to diet, vitamin supplements, and regular monitoring. AMD has a complex pathogenesis, involving highly integrated and common age-related disease pathways, including dysregulated complement/inflammation, impaired autophagy, and oxidative stress. The intricacy of AMD pathogenesis makes therapeutic development challenging and identifying a target that combats the converging disease pathways is essential to provide a globally effective treatment. Interleukin-33 is a cytokine, classically known for the proinflammatory role it plays in allergic disease. Recent evidence across degenerative and inflammatory disease conditions reveals a diverse immune-modulatory role for IL-33, with promising therapeutic potential. Here, we will review IL-33 function in disease and discuss the future potential for this homeostatic cytokine in treating AMD., (© 2021. The Author(s).)
- Published
- 2022
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44. Study of Xbal and Pvull polymorphisms of estrogen receptor alpha (ERα) gene in girls with precocious/early puberty.
- Author
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Theodoropoulou S, Papadopoulou A, Karapanou O, Priftis K, Papaevangelou V, and Papadimitriou A
- Subjects
- Child, Female, Genotype, Greece, Humans, Polymorphism, Genetic, Estrogen Receptor alpha genetics, Puberty, Precocious genetics
- Abstract
Purpose: Studies examining association of estrogen receptor alpha (ERα) polymorphisms with early puberty are scarce and results are controversial; data in Caucasian girls are lacking. Main objective was to determine association of Xbal and Pvull polymorphisms of ERα gene in Greek girls with precocious/early puberty METHODS: We studied 107 girls with idiopathic precocious/early puberty and 81 young women with pubertal maturation within normal age (controls). Pubertal stage, height SDS (HSDS), and BMI z-score were determined in patients. In controls, height was measured and menarcheal age was self-reported. All participants in the study were genotyped for XbaI and PvuII polymorphisms of the ERα gene., Results: There was no significant difference in XbaI and PvuII polymorphisms between patients and controls. Homozygous, xx and pp, girls had an earlier onset of puberty, although non-significant, than heterozygous or with no polymorphisms p = 0.9; in girls with pubertal onset <7 years, the association tended to become significant, p = 0.09. Girls with xxpp genotype were significantly taller, HSDS 1.63, p = 0.014. In controls, homozygosity for Xbal (xx) and PvuII (pp) was associated with significantly earlier menarche than in women with no polymorphism, p = 0.013 and p = 0.026, respectively, and xxpp genotype was associated with taller adult height, p = 0.017., Conclusion: XbaI and PvuII polymorphisms are not related to idiopathic precocious/early puberty. Early pubertal girls homozygous for both polymorphisms presented earlier onset of puberty, although statistically non-significant, and taller height than girls heterozygous or without these polymorphisms. Homozygosity for both polymorphisms is associated with earlier menarche and taller adult height.
- Published
- 2021
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45. Interleukin-33 regulates metabolic reprogramming of the retinal pigment epithelium in response to immune stressors.
- Author
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Scott LM, Vincent EE, Hudson N, Neal C, Jones N, Lavelle EC, Campbell M, Halestrap AP, Dick AD, and Theodoropoulou S
- Subjects
- Animals, Cell Line, Cell Proliferation, Cell Survival, Energy Metabolism, Gene Knockdown Techniques, Glycolysis drug effects, Humans, Hydrogen Peroxide pharmacology, Interferon Inducers pharmacology, Interleukin-33 drug effects, Interleukin-33 genetics, Lipopolysaccharides pharmacology, Mice, Mice, Knockout, Mitochondria drug effects, Oxidants pharmacology, Oxidation-Reduction drug effects, Oxidative Stress, Poly I-C pharmacology, Primary Cell Culture, Pyruvic Acid metabolism, Cell Respiration physiology, Glycolysis physiology, Interleukin-33 metabolism, Mitochondria metabolism, Retinal Pigment Epithelium metabolism
- Abstract
It remains unresolved how retinal pigment epithelial cell metabolism is regulated following immune activation to maintain retinal homeostasis and retinal function. We exposed retinal pigment epithelium (RPE) to several stress signals, particularly Toll-like receptor stimulation, and uncovered an ability of RPE to adapt their metabolic preference on aerobic glycolysis or oxidative glucose metabolism in response to different immune stimuli. We have identified interleukin-33 (IL-33) as a key metabolic checkpoint that antagonizes the Warburg effect to ensure the functional stability of the RPE. The identification of IL-33 as a key regulator of mitochondrial metabolism suggests roles for the cytokine that go beyond its extracellular "alarmin" activities. IL-33 exerts control over mitochondrial respiration in RPE by facilitating oxidative pyruvate catabolism. We have also revealed that in the absence of IL-33, mitochondrial function declined and resultant bioenergetic switching was aligned with altered mitochondrial morphology. Our data not only shed new light on the molecular pathway of activation of mitochondrial respiration in RPE in response to immune stressors but also uncover a potentially novel role of nuclear intrinsic IL-33 as a metabolic checkpoint regulator.
- Published
- 2021
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46. Treatment with interleukin-33 is non-toxic and protects retinal pigment epithelium in an ageing model of outer retinal degeneration.
- Author
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Clare AJ, Copland DA, Nicholson LB, Liu J, Neal CR, Moss S, Dick AD, and Theodoropoulou S
- Subjects
- Animals, Disease Models, Animal, Humans, Immunohistochemistry, Macular Degeneration etiology, Macular Degeneration metabolism, Macular Degeneration pathology, Mice, Mice, Knockout, Retinal Degeneration drug therapy, Retinal Degeneration pathology, Retinal Pigment Epithelium pathology, Retinal Pigment Epithelium ultrastructure, Treatment Outcome, Aging genetics, Aging metabolism, Interleukin-33 pharmacology, Retinal Degeneration etiology, Retinal Degeneration metabolism, Retinal Pigment Epithelium drug effects, Retinal Pigment Epithelium metabolism
- Abstract
The leading cause of central vision loss, age-related macular degeneration (AMD), is a degenerative disorder characterized by atrophy of retinal pigment epithelium (RPE) and photoreceptors. For 15% of cases, neovascularization occurs, leading to acute vision loss if left untreated. For the remaining patients, there are currently no treatment options and preventing progressive RPE atrophy remains the main therapeutic goal. Previously, we have shown treatment with interleukin-33 can reduce choroidal neovascularization and attenuate tissue remodelling. Here, we investigate IL-33 delivery in aged, high-fat diet (HFD) fed mice on a wildtype and complement factor H heterozygous knockout background. We characterize the non-toxic effect following intravitreal injection of IL-33 and further demonstrate protective effects against RPE cell death with evidence of maintaining metabolic retinal homeostasis of Cfh+/-~HFD mice. Our results further support the potential utility of IL-33 to prevent AMD progression., (© 2020 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)
- Published
- 2020
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47. Treatment of diabetic retinopathy through neuropeptide Y-mediated enhancement of neurovascular microenvironment.
- Author
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Ou K, Copland DA, Theodoropoulou S, Mertsch S, Li Y, Liu J, Schrader S, Liu L, and Dick AD
- Subjects
- Animals, Apoptosis drug effects, Cellular Microenvironment drug effects, Diabetes Mellitus, Experimental drug therapy, Diabetes Mellitus, Experimental genetics, Diabetes Mellitus, Experimental pathology, Diabetic Retinopathy genetics, Diabetic Retinopathy pathology, Endothelial Cells drug effects, Humans, Mice, N-Methylaspartate pharmacology, Neuropeptide Y genetics, Rats, Retina drug effects, Retina pathology, Retinal Ganglion Cells drug effects, Retinal Ganglion Cells pathology, Retinal Neovascularization genetics, Retinal Neovascularization pathology, Vascular Endothelial Growth Factor A pharmacology, Diabetic Retinopathy drug therapy, N-Methylaspartate genetics, Neuropeptide Y pharmacology, Retinal Neovascularization drug therapy, Vascular Endothelial Growth Factor A genetics
- Abstract
Diabetic retinopathy (DR) is one of the most severe clinical manifestations of diabetes mellitus and a major cause of blindness. DR is principally a microvascular disease, although the pathogenesis also involves metabolic reactive intermediates which induce neuronal and glial activation resulting in disruption of the neurovascular unit and regulation of the microvasculature. However, the impact of neural/glial activation in DR remains controversial, notwithstanding our understanding as to when neural/glial activation occurs in the course of disease. The objective of this study was to determine a potential protective role of neuropeptide Y (NPY) using an established model of DR permissive to N-methyl-D-aspartate (NMDA)-induced excitotoxic apoptosis of retinal ganglion cells (RGC) and vascular endothelial growth factor (VEGF)-induced vascular leakage. In vitro evaluation using primary retinal endothelial cells demonstrates that NPY promotes vascular integrity, demonstrated by maintained tight junction protein expression and reduced permeability in response to VEGF treatment. Furthermore, ex vivo assessment of retinal tissue explants shows that NPY can protect RGC from excitotoxic-induced apoptosis. In vivo clinical imaging and ex vivo tissue analysis in the diabetic model permitted assessment of NPY treatment in relation to neural and endothelial changes. The neuroprotective effects of NPY were confirmed by attenuating NMDA-induced retinal neural apoptosis and able to maintain inner retinal vascular integrity. These findings could have important clinical implications and offer novel therapeutic approaches for the treatment in the early stages of DR., (© 2020 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)
- Published
- 2020
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48. Corrigendum to "Restoring retinal neurovascular health via substance P" [Exp. Cell Res. (2019)].
- Author
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Ou K, Mertsch S, Theodoropoulou S, Wu J, Liu J, Copland DA, Schrader S, Liu L, and Dick AD
- Published
- 2019
- Full Text
- View/download PDF
49. Dysregulated claudin-5 cycling in the inner retina causes retinal pigment epithelial cell atrophy.
- Author
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Hudson N, Celkova L, Hopkins A, Greene C, Storti F, Ozaki E, Fahey E, Theodoropoulou S, Kenna PF, Humphries MM, Curtis AM, Demmons E, Browne A, Liddie S, Lawrence MS, Grimm C, Cahill MT, Humphries P, Doyle SL, and Campbell M
- Subjects
- Animals, Blood-Retinal Barrier diagnostic imaging, Blood-Retinal Barrier drug effects, Capillary Permeability drug effects, Capillary Permeability physiology, Chlorocebus aethiops, Claudin-5 genetics, Diet, High-Fat adverse effects, Disease Models, Animal, Fluorescein Angiography, Fundus Oculi, Gene Knockdown Techniques, Geographic Atrophy drug therapy, Geographic Atrophy etiology, Geographic Atrophy prevention & control, Healthy Volunteers, Humans, Magnetic Resonance Imaging, Mice, Mice, Transgenic, Photoperiod, RNA, Small Interfering metabolism, Retinal Pigment Epithelium drug effects, Retinal Pigment Epithelium pathology, ARNTL Transcription Factors metabolism, Blood-Retinal Barrier pathology, Circadian Clocks physiology, Claudin-5 metabolism, Geographic Atrophy pathology
- Abstract
Age-related macular degeneration (AMD) is the leading cause of central retinal vision loss worldwide, with an estimated 1 in 10 people over the age of 55 showing early signs of the condition. There are currently no forms of therapy available for the end stage of dry AMD, geographic atrophy (GA). Here, we show that the inner blood-retina barrier (iBRB) is highly dynamic and may play a contributory role in GA development. We have discovered that the gene CLDN5, which encodes claudin-5, a tight junction protein abundantly expressed at the iBRB, is regulated by BMAL1 and the circadian clock. Persistent suppression of claudin-5 expression in mice exposed to a cholesterol-enriched diet induced striking retinal pigment epithelium (RPE) cell atrophy, and persistent targeted suppression of claudin-5 in the macular region of nonhuman primates induced RPE cell atrophy. Moreover, fundus fluorescein angiography in human and nonhuman primate subjects showed increased retinal vascular permeability in the evening compared with the morning. These findings implicate an inner retina-derived component in the early pathophysiological changes observed in AMD, and we suggest that restoring the integrity of the iBRB may represent a novel therapeutic target for the prevention and treatment of GA secondary to dry AMD.
- Published
- 2019
- Full Text
- View/download PDF
50. Restoring retinal neurovascular health via substance P.
- Author
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Ou K, Mertsch S, Theodoropoulou S, Wu J, Liu J, Copland DA, Schrader S, Liu L, and Dick AD
- Subjects
- Animals, Apoptosis drug effects, Blood-Retinal Barrier drug effects, Blood-Retinal Barrier metabolism, Cells, Cultured, Mice, Mice, Inbred C57BL, N-Methylaspartate administration & dosage, N-Methylaspartate pharmacology, Rats, Rats, Wistar, Retina drug effects, Retina metabolism, Vascular Endothelial Growth Factors metabolism, Retinal Neovascularization metabolism, Substance P metabolism
- Abstract
Regulation of vascular permeability plays a major role in the pathophysiology of visually threatening conditions such as retinal vein occlusion and diabetic retinopathy. Principally, several factors such as vascular endothelial growth factor (VEGF), are up-regulated or induced in response to hypoxia thus adversely affecting the blood-retinal barrier (BRB), resulting in retinal edema and neovascularisation. Furthermore, current evidence supports a dysregulation of the inner retinal neural-vascular integrity as a critical factor driving retinal ganglion cell (RGC) death and visual loss. The principal objective of this study was to interrogate whether Substance P (SP), a constitutive neurotransmitter of amacrine and ganglion cells, may protect against N-methyl-d-aspartate (NMDA)-induced excitotoxic apoptosis of ganglion cells and VEGF-induced vessel leakage in the retina. Tight junctional protein expression and a Vascular Permeability Image Assay were used to determine vascular integrity in vitro. The protective effect of SP on RGC was established in ex vivo retinal explants and in vivo murine models. After NMDA administration, a reduction in TUNEL+ cells and a maintained number of Brn-3a+ cells were found, indicating an inhibition of RGC apoptosis mediated by SP. Additionally, SP maintained endothelial tight junctions and decreased VEGF-induced vascular permeability. In conclusion, administration of SP protects against NMDA apoptosis of RGC and VEGF-induced endothelial barrier breakdown., (Copyright © 2019. Published by Elsevier Inc.)
- Published
- 2019
- Full Text
- View/download PDF
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