319 results on '"Goran Petrovski"'
Search Results
52. Tailoring cells for clinical needs: Meeting report from the Advanced Therapy in Healthcare symposium (October 28–29 2017, Doha, Qatar)
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Sara Deola, Bella S. Guerrouahen, Heba Sidahmed, Anjud Al-Mohannadi, Muhammad Elnaggar, Ramaz Elsadig, Essam M. Abdelalim, Goran Petrovski, Massimo Gadina, Adrian Thrasher, Winfried S. Wels, Stephen P. Hunger, Ena Wang, Francesco M. Marincola, ATH Consortium, Cristina Maccalli, and Chiara Cugno
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Personalized medicine ,Cell therapy ,Gene therapy ,Stem cells ,Autoimmunity ,Oncology ,Medicine - Abstract
Abstract New technologies and therapies designed to facilitate development of personalized treatments are rapidly emerging in the field of biomedicine. Strikingly, the goal of personalized medicine refined the concept of therapy by developing cell-based therapies, the so-called “living drugs”. Breakthrough advancements were achieved in this regard in the fields of gene therapy, cell therapy, tissue-engineered products and advanced therapeutic techniques. The Advanced Therapies in Healthcare symposium, organized by the Clinical Research Center Department of Sidra Medicine, in Doha, Qatar (October 2017), brought together world-renowned experts from the fields of oncology, hematology, immunology, inflammation, autoimmune disorders, and stem cells to offer a comprehensive picture of the status of worldwide advanced therapies in both pre-clinical and clinical development, providing insights to the research phase, clinical data and regulatory aspects of these therapies. Highlights of the meeting are provided in this meeting report.
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- 2018
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53. Hsp90 inhibition as a means to inhibit activation of the NLRP3 inflammasome
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Niina Piippo, Eveliina Korhonen, Maria Hytti, Heli Skottman, Kati Kinnunen, Natasha Josifovska, Goran Petrovski, Kai Kaarniranta, and Anu Kauppinen
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Medicine ,Science - Abstract
Abstract Once activated, the intracellular receptor NLRP3 assembles an inflammasome protein complex that facilitates the caspase-1-mediated maturation of IL-1β and IL-18. Inactive NLRP3 is guarded by a protein complex containing Hsp90. In response to stress stimuli, Hsp90 is released, and NLRP3 can be activated to promote inflammation. In this study, we blocked Hsp90 with geldanamycin and studied the fate of NLRP3 in human retinal pigment epithelial (RPE) cells. RPE cells play a central role in the development of age-related macular degeneration (AMD), a progressive eye disease causing severe vision loss in the elderly. IL-1α-primed ARPE-19 cells, human embryonal stem cell (hESC)-derived RPE cells, and primary human RPE cells were exposed to MG-132 and bafilomycin A to activate NLRP3 via the inhibition of proteasomes and autophagy, respectively. Additionally, RPE cells were treated with geldanamycin at different time points and the levels of NLRP3 and IL-1β were determined. Caspase-1 activity was measured using a commercial assay. Geldanamycin prevented the activation of the inflammasome in human RPE cells. NLRP3 released from its protective complex became degraded by autophagy or secreted from the cells. Controlled destruction of NLRP3 is a potential way to regulate the inflammation associated with chronic diseases, such as AMD.
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- 2018
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54. Comparative proteomic analysis of human embryonic stem cell-derived and primary human retinal pigment epithelium
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Heidi Hongisto, Antti Jylhä, Janika Nättinen, Jochen Rieck, Tanja Ilmarinen, Zoltán Veréb, Ulla Aapola, Roger Beuerman, Goran Petrovski, Hannu Uusitalo, and Heli Skottman
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Medicine ,Science - Abstract
Abstract Human embryonic stem cell-derived retinal pigment epithelial cells (hESC-RPE) provide an unlimited cell source for retinal cell replacement therapies. Clinical trials using hESC-RPE to treat diseases such as age-related macular degeneration (AMD) are currently underway. Human ESC-RPE cells have been thoroughly characterized at the gene level but their protein expression profile has not been studied at larger scale. In this study, proteomic analysis was used to compare hESC-RPE cells differentiated from two independent hESC lines, to primary human RPE (hRPE) using Isobaric tags for relative quantitation (iTRAQ). 1041 common proteins were present in both hESC-RPE cells and native hRPE with majority of the proteins similarly regulated. The hESC-RPE proteome reflected that of normal hRPE with a large number of metabolic, mitochondrial, cytoskeletal, and transport proteins expressed. No signs of increased stress, apoptosis, immune response, proliferation, or retinal degeneration related changes were noted in hESC-RPE, while important RPE specific proteins involved in key RPE functions such as visual cycle and phagocytosis, could be detected in the hESC-RPE. Overall, the results indicated that the proteome of the hESC-RPE cells closely resembled that of their native counterparts.
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- 2017
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55. The clinical and genetic characteristics of permanent neonatal diabetes (PNDM) in the state of Qatar
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Sara Al‐Khawaga, Idris Mohammed, Saras Saraswathi, Basma Haris, Reem Hasnah, Amira Saeed, Hakeem Almabrazi, Najeeb Syed, Puthen Jithesh, Ahmed El Awwa, Amal Khalifa, Fawziya AlKhalaf, Goran Petrovski, Essam M. Abdelalim, and Khalid Hussain
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Fanconi–Bickel Syndrome (FBS) ,GCK ,HNF1B ,INS ,pancreatic agenesis ,Permanent neonatal diabetes (PNDM) ,Genetics ,QH426-470 - Abstract
Abstract Background Neonatal diabetes mellitus (NDM) is a rare condition that occurs within the first six months of life. Permanent NDM (PNDM) is caused by mutations in specific genes that are known for their expression at early and/or late stages of pancreatic beta‐ cell development, and are either involved in beta‐cell survival, insulin processing, regulation, and release. The native population in Qatar continues to practice consanguineous marriages that lead to a high level of homozygosity. To our knowledge, there is no previous report on the genomics of NDM among the Qatari population. The aims of the current study are to identify patients with NDM diagnosed between 2001 and 2016, and examine their clinical and genetic characteristics. Methods To calculate the incidence of PNDM, all patients with PNDM diagnosed between 2001 and 2016 were compared to the total number of live births over the 16‐year‐period. Whole Genome Sequencing (WGS) was used to investigate the genetic etiology in the PNDM cohort. Results PNDM was diagnosed in nine (n = 9) patients with an estimated incidence rate of 1:22,938 live births among the indigenous Qatari. Seven different mutations in six genes (PTF1A, GCK, SLC2A2, EIF2AK3, INS, and HNF1B) were identified. In the majority of cases, the genetic etiology was part of a previously identified autosomal recessive disorder. Two novel de novo mutations were identified in INS and HNF1B. Conclusion Qatar has the second highest reported incidence of PNDM worldwide. A majority of PNDM cases present as rare familial autosomal recessive disorders. Pancreas associated transcription factor 1a (PTF1A) enhancer deletions are the most common cause of PNDM in Qatar, with only a few previous cases reported in the literature.
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- 2019
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56. Clinical and molecular markers in retinal detachment-From hyperreflective points to stem cells and inflammation.
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Natasha Josifovska, Xhevat Lumi, Mária Szatmari-Tóth, Endre Kristóf, Greg Russell, Richárd Nagymihály, Natalia Anisimova, Boris Malyugin, Miriam Kolko, Domagoj Ivastinović, and Goran Petrovski
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Medicine ,Science - Abstract
PurposeRetinal detachment (RD) is one of the most frequently diagnosed ophthalmologic conditions requiring prompt surgical intervention. Combination of proper surgical technique and new diagnostic markers, both clinical and molecular, can help improve the diagnosis and prognosis of RD treatment.Methods12 patients with rhegmatogenous RD (rRD) were included into the study after obtaining patient consent and Regional Ethical Approval (average age: 58.1 ± 17.4 years). OCT was performed before and after 23G vitrectomy for RD. Pure subretinal fluid (SRF) was collected during surgery and analyzed by protein array profiling on a panel of 105 inflammatory cytokines (Human XL Cytokine Array), while the effect of SRF upon human macrophages-driven phagocytosis of apoptotic retinal pigment epithelial (RPE) cells ex vivo was quantified by flow cytometry. Immunohistochemistry (IHC) of retinectomized tissue due to PVR caused by RD was performed to determine presence of markers for microglial cells (CD34), macrophages and activated microglia (CD68), regulator of the immune response to infection (NFkB), progenitor and stem cell marker (Sox2), pluripotency marker (Oct4) and intermediate filament markers (GFAP and Nestin).ResultsOCT of fresh RD patients contained pre-operatively hyper reflective points (HRPs) at the detached neuroretina border and proximal to the RPE layer-their size and number decreased following successful reattachment surgery. IHC of the retinectomized tissue from detached retina due to severe PVR showed presence of cell conglomerates at the detached neuroretina border which were positive for CD68, NFkB, Sox2 and GFAP, less positive for CD47 and Nestin and negative for Oct4 and CD34. The SRF contained at least 37 cytokines with higher, and 4 cytokine with lower concentration compared to that in vitreous from non-RD pathology; when used as conditional medium to human macrophages ex vivo, the SRF doubled their capacity for engulfing dying RPEs.ConclusionsFresh RD can be hallmarked by presence of HRPs at the detached neuroretina border on OCT; the HRPs decrease in size and number after successful reattachment surgery, and likely resemble the macrophage conglomerates seen by IHC. The neuroretina in RD contains progenitor/stem-like cells and signs of inflammatory reaction, while the SRF contains inflammatory cytokines and other factors which increase the ability of professional phagocytes to engulf dying RPE, or for that matter, other dying cells in the retina.
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- 2019
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57. Akkermansia, a Possible Microbial Marker for Poor Glycemic Control in Qataris Children Consuming Arabic Diet—A Pilot Study on Pediatric T1DM in Qatar
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Arun Prasath Lakshmanan, Amira Kohil, Farah El Assadi, Sara Al Zaidan, Shaikha Al Abduljabbar, Dhinoth Kumar Bangarusamy, Fawziya Al Khalaf, Goran Petrovski, and Annalisa Terranegra
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Akkermansia ,T1DM ,Arabic diet ,ethnicity ,HbA1c ,CSII therapy ,Nutrition. Foods and food supply ,TX341-641 - Abstract
In Qatar, Type 1 Diabetes mellitus (T1DM) is one of the most prevalent disorders. This study aimed to explore the gut microbiome’s relation to the continuous subcutaneous insulin infusion (CSII) therapy, dietary habits, and the HbA1c level in the pediatric T1DM subjects in Qatar. We recruited 28 T1DM subjects with an average age of 10.5 ± 3.53 years. The stool sample was used to measure microbial composition by 16s rDNA sequencing method. The results have revealed that the subjects who had undergone CSII therapy had increased microbial diversity and genus Akkermansia was significantly enriched in the subjects without CSII therapy. Moreover, genus Akkermansia was higher in the subjects with poor glycemic control (HbA1c > 7.5%). When we classified the subjects based on dietary patterns and nationality, Akkermansia was significantly enriched in Qataris subjects without the CSII therapy consuming Arabic diet than expatriates living in Qatar and eating a Western/mixed diet. Thus, this pilot study showed that abundance of Akkermansia is dependent on the Arabic diet only in poorly controlled Qataris T1DM patients, opening new routes to personalized treatment for T1DM in Qataris pediatric subjects. Further comprehensive studies on the relation between the Arabic diet, ethnicity, and Akkermansia are warranted to confirm this preliminary finding.
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- 2021
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58. Resveratrol as Inducer of Autophagy, Pro-Survival, and Anti-Inflammatory Stimuli in Cultured Human RPE Cells
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Natasha Josifovska, Réka Albert, Richárd Nagymihály, Lyubomyr Lytvynchuk, Morten C. Moe, Kai Kaarniranta, Zoltán J. Veréb, and Goran Petrovski
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resveratrol ,retinal pigment epithelium ,autophagy ,proteasomal inhibition ,survival ,inflammation ,protein array ,age-related macular degeneration ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
Purpose: To investigate the mechanism by which resveratrol acts upon retinal pigment epithelial (RPE) cells and to characterize its effect upon autophagy, survival, and inflammation, with consequent implications to treatment for age-related macular degeneration (AMD). Methods: Cultured ARPE-19 cells were exposed to 10 and 50 μM resveratrol. Cell survival/death was determined by annexin-FITC/propidium iodide using flow cytometry, while autophagy was studied by detecting autophagic vacuoles formation (acridine orange and transmission electron microscopy), as well as LC3II/I ratio and p62 expression by Western blot. In addition, time-lapse confocal microscopy of a pDENDRA-LC3 expression vector was performed to detect autophagy in transfected ARPE-19 cells under the different treatment conditions. Inhibition of proteasomal and autophagy-lysosomal fusion was carried out by MG-132 and chloroquine, respectively, while induction of autophagy was achieved by rapamycin treatment. Detection of secreted cytokines by ARPE-19 cells using Human XL Cytokine Array was performed under oxidative stress (H2O2) and resveratrol treatments, respectively. Results: Resveratrol induced autophagy in ARPE-19 cells as determined by augmented presence of autophagic vacuoles, increased LC3II/I ratio and decreased p62 expression, as well as time-lapse confocal microscopy using pDENDRA-LC3 expression vector. Resveratrol acted similarly to proteasomal inhibition and downstream of mammalian target of rapamycin (mTOR), since upstream inhibition of autophagy by 3-methyladenine could not inhibit autophagy in ARPE-19 cells. Co-treatmeant by rapamycin and/or proteasome inhibition showed no additive effect upon autophagy induction. ARPE-19 cells treated by resveratrol showed lower cell death rate compared to untreated controls. Resveratrol induced a specific anti-inflammatory response in ARPE-19 cells. Conclusions: Resveratrol can induce autophagy, pro-survival, and anti-inflammatory stimuli in ARPE-19 cells, properties which could be plausible to formulate future treatment modalities for AMD.
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- 2020
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59. Expression of Progenitor Cell Markers in the Glial-Like Cells of Epiretinal Membranes of Different Origins
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Xiaohe Yan, Pål Andresen, Xhevat Lumi, Qingshan Chen, and Goran Petrovski
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Ophthalmology ,RE1-994 - Abstract
Purpose. To investigate the expression of progenitor cell markers (Sox2, Nestin, and Pax2) in idiopathic epiretinal membranes (iERMs) and nonidiopathic epiretinal membranes (niERMs) in relation to glial cell marker expression. Methods. ERMs were obtained from patients with iERMs and niERMs of different origins: proliferative diabetic retinopathy (PDR), proliferative vitreoretinopathy (PVR), and uveitis. The membranes were studied by flat-mount or sectional immunohistochemistry for expression of progenitor cell markers as well as glial (GFAP) and proliferation (Ki-67) markers. Results. Cells in the ERMs express strong GFAP, with strong Pax2 expression in the cell nuclei. Some of the GFAP-positive glial cells in all epiretinal membrane types colocalized with Sox2, Pax2, and Nestin. NiERMs are much more cellular than iERMs. Glial cells are more densely packed in all analyzed niERMs, whereas glial cells with long branches are found in the internal limiting membrane parts and the iERMs, which appear to form a local network by their processes. Conclusion. The GFAP-positive glial cells in ERMs are not pure glial cells, and some of them express progenitor cell markers, which indicate that these cells may have potential for self-renewal and differentiation into more glial or neuroglial type of cells.
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- 2018
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60. Comparative cyto-histological study of needle tip aspirates and entry sites after intravitreal injection using different needle types.
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Lyubomyr Lytvynchuk, Andrij Sergienko, Iryna Savytska, Réka Albert, Carl Glittenberg, Susanne Binder, and Goran Petrovski
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Medicine ,Science - Abstract
A comparison of the cellular content of needle tip aspirates and entry sites after transconjunctival intravitreal injection (IVI) using different needle types was performed. White outbred rats and human cadaver eyes were used for IVI by hypodermic 27 gauge (G) and 30G needles, and spinal anesthesia Pencan 27G needles. Aspiration of vitreous for quantitative morphological and cell cultivation analysis, as well as cyto-histological analysis of aspirates and entry sites were carried out. The most common cells in the aspirates from all needle types were conjunctival epithelial-, ciliary body non-pigmented epithelial- and sclerocyte-like cells and granular proteins. Crystallized vitreous specimens were present in each aspirate. The entry sites of hypodermic needles showed marked trauma in all wall layers of rat and human eyes accompanied by cellular destruction and hemorrhages. Pencan 27G needle caused less tissue trauma with partial reposition of sclerocytes. Transconjunctival IVIs with hypodermic 27G and 30G, and Pencan 27G needles result in trauma of all layers of the eyeball. The possible consequences of cellular content being cut and injected into the eye, as well as the entry site wound shape deserve future consideration and improvements.
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- 2017
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61. Oxidative Stress, Epigenetics, Environment, and Epidemiology of Diabetic Retinopathy
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Goran Petrovski, Kai Kaarniranta, and Daniel Petrovič
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Diseases of the endocrine glands. Clinical endocrinology ,RC648-665 - Published
- 2017
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62. Vitreous hyper-reflective dots in pseudophakic cystoid macular edema assessed with optical coherence tomography.
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Wilfried Glatz, Gernot Steinwender, Lisa Tarmann, Eva Maria Malle, Marlene Schörkhuber, Werner Wackernagel, Goran Petrovski, Andreas Wedrich, and Domagoj Ivastinovic
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Medicine ,Science - Abstract
This study compares the presence of vitreous hyper-reflective dots (VHDs) detected with optical coherence tomography (OCT) between eyes with pseudophakic cystoid macular edema (CME) and those with no CME after cataract surgery. In addition, we evaluated the impact of VHDs on the responsiveness of pseudophakic CME to cortisone treatment.Department of Ophthalmology, Medical University of Graz, Austria.Retrospective, monocenter case-controlled study.Inclusion criteria for the study group and the control group were CME and no CME within 12 weeks following uneventful phacoemulsification in otherwise healthy eyes, respectively. VHDs (number and size) and the macular thickness were assessed with OCT. Furthermore, the number of peribulbar or intravitreal steroid injections was assessed.A total of 284 eyes from 267 patients were analyzed, among which 119 met the inclusion criteria for the study (n = 63) and the control group (n = 56). VHDs were observed in 54 (85.7%) study eyes and 21 (37.5%, p = 0.013) control eyes. The number of VHDs was 3.9±3.4 in the study group and 0.7±1 in the control group (p
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- 2017
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63. Effect of Isolation Technique and Location on the Phenotype of Human Corneal Stroma-Derived Cells
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Richárd Nagymihály, Zoltán Veréb, Andrea Facskó, Morten C. Moe, and Goran Petrovski
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Internal medicine ,RC31-1245 - Abstract
Purpose. To determine the effect of the isolation technique and location upon the phenotype of human corneal stroma-derived cells (CSCs). Methods. CSCs were isolated from the corneal stroma center and periphery using the explant or enzymatic digestion technique. The native tissue was stained for functional markers, while cultured cells were analysed by FACS. PCR was used to determine gene expression in the cultured versus native cells. Results. The native stroma was positive for α-actinin, ALDH1A1, CD31, CD34, Collagen I, and Vimentin. Cultured cells expressed CD73, CD90, CD105, CD51, Nestin, CD49a, CD49d, ABCG2, and CD47. PCR demonstrated a significant upregulation of ALDH1A1, AQP1, ITGB4, KLF4, CD31, CD34, and CXCR4 in the native tissue, while the expression of ABCG2, ITGAV, Nestin, CD73, CD90, CD105, and Vimentin were significantly higher in the cultured cells. GPC did not change. Conclusion. The study finds no significant difference between the phenotype of CSCs generated by the explant or enzymatic digestion technique from the center or periphery of the stroma. Isolation of the cells can be performed without regard to the location and isolation technique used for research. Cultivated CSCs undergo a complete surface marker and genotype profile change compared to the state in situ.
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- 2017
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64. Human Embryonic Stem Cell-Derived Retinal Pigment Epithelium-Role in Dead Cell Clearance and Inflammation
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Mária Szatmári-Tóth, Tanja Ilmarinen, Alexandra Mikhailova, Heli Skottman, Anu Kauppinen, Kai Kaarniranta, Endre Kristóf, Lyubomyr Lytvynchuk, Zoltán Veréb, László Fésüs, and Goran Petrovski
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age-related macular degeneration ,anoikis ,autophagy ,hESC-RPE ,inflammation ,macrophages ,phagocytosis ,triamcinolone ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
Inefficient removal of dying retinal pigment epithelial (RPE) cells by professional phagocytes can result in debris formation and development of age-related macular degeneration (AMD). Chronic oxidative stress and inflammation play an important role in AMD pathogenesis. Only a few well-established in vitro phagocytosis assay models exist. We propose human embryonic stem cell-derived-RPE cells as a new model for studying RPE cell removal by professional phagocytes. The characteristics of human embryonic stem cells-derived RPE (hESC-RPE) are similar to native RPEs based on their gene and protein expression profile, integrity, and barrier properties or regarding drug transport. However, no data exist about RPE death modalities and how efficiently dying hESC-RPEs are taken upby macrophages, and whether this process triggers an inflammatory responses. This study demonstrates hESC-RPEs can be induced to undergo anoikis or autophagy-associated cell death due to extracellular matrix detachment or serum deprivation and hydrogen-peroxide co-treatment, respectively, similar to primary human RPEs. Dying hESC-RPEs are efficiently engulfed by macrophages which results in high amounts of IL-6 and IL-8 cytokine release. These findings suggest that the clearance of anoikic and autophagy-associated dying hESC-RPEs can be used as a new model for investigating AMD pathogenesis or for testing the in vivo potential of these cells in stem cell therapy.
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- 2019
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65. Microplasma Induced Cell Morphological Changes and Apoptosis of Ex Vivo Cultured Human Anterior Lens Epithelial Cells - Relevance to Capsular Opacification.
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Nina Recek, Sofija Andjelić, Nataša Hojnik, Gregor Filipič, Saša Lazović, Alenka Vesel, Gregor Primc, Miran Mozetič, Marko Hawlina, Goran Petrovski, and Uroš Cvelbar
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Medicine ,Science - Abstract
Inducing selective or targeted cell apoptosis without affecting large number of neighbouring cells remains a challenge. A plausible method for treatment of posterior capsular opacification (PCO) due to remaining lens epithelial cells (LECs) by reactive chemistry induced by localized single electrode microplasma discharge at top of a needle-like glass electrode with spot size ~3 μm is hereby presented. The focused and highly-localized atmospheric pressure microplasma jet with electrode discharge could induce a dose-dependent apoptosis in selected and targeted individual LECs, which could be confirmed by real-time monitoring of the morphological and structural changes at cellular level. Direct cell treatment with microplasma inside the medium appeared more effective in inducing apoptosis (caspase 8 positivity and DNA fragmentation) at a highly targeted cell level compared to treatment on top of the medium (indirect treatment). Our results show that single cell specific micropipette plasma can be used to selectively induce demise in LECs which remain in the capsular bag after cataract surgery and thus prevent their migration (CXCR4 positivity) to the posterior lens capsule and PCO formation.
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- 2016
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66. Long-Term Cultures of Human Cornea Limbal Explants Form 3D Structures Ex Vivo - Implications for Tissue Engineering and Clinical Applications.
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Dóra Júlia Szabó, Agate Noer, Richárd Nagymihály, Natasha Josifovska, Sofija Andjelic, Zoltán Veréb, Andrea Facskó, Morten C Moe, and Goran Petrovski
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Medicine ,Science - Abstract
Long-term cultures of cornea limbal epithelial stem cells (LESCs) were developed and characterized for future tissue engineering and clinical applications. The limbal tissue explants were cultivated and expanded for more than 3 months in medium containing serum as the only growth supplement and without use of scaffolds. Viable 3D cell outgrowth from the explants was observed within 4 weeks of cultivation. The outgrowing cells were examined by immunofluorescent staining for putative markers of stemness (ABCG2, CK15, CK19 and Vimentin), proliferation (p63α, Ki-67), limbal basal epithelial cells (CK8/18) and differentiated cornea epithelial cells (CK3 and CK12). Morphological and immunostaining analyses revealed that long-term culturing can form stratified 3D tissue layers with a clear extracellular matrix deposition and organization (collagen I, IV and V). The LESCs showed robust expression of p63α, ABCG2, and their surface marker fingerprint (CD117/c-kit, CXCR4, CD146/MCAM, CD166/ALCAM) changed over time compared to short-term LESC cultures. Overall, we provide a model for generating stem cell-rich, long-standing 3D cultures from LESCs which can be used for further research purposes and clinical transplantation.
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- 2015
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67. Antiproliferative, Apoptotic, and Autophagic Activity of Ranibizumab, Bevacizumab, Pegaptanib, and Aflibercept on Fibroblasts: Implication for Choroidal Neovascularization
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Lyubomyr Lytvynchuk, Andrii Sergienko, Galina Lavrenchuk, and Goran Petrovski
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Ophthalmology ,RE1-994 - Abstract
Purpose. Choroidal neovascularization (CNV) is one of the most common complications of retinal diseases accompanied by elevated secretion of vascular endothelial growth factor (VEGF). Intravitreal anti-VEGFs (ranibizumab, bevacizumab, pegaptanib, and aflibercept) can suppress neovascularization, decrease vascular permeability and CNV size, and, thereby, improve visual function. The antiproliferative, apoptotic, and autophagic effect of anti-VEGF drugs on fibroblasts found in CNVs has not been yet explored. Methods. Concentration-dependent cellular effects of the four anti-VEGFs were examined in L929 fibroblasts over a 5-day period. The cell survival, mitotic and polykaryocytic indices, the level of apoptosis and autophagy, and the cellular growth kinetics were all assessed. Results. The anti-VEGFs could inhibit the survival, mitotic activity, and proliferation as well as increase the cellular heterogeneity, apoptosis, and autophagy of the fibroblasts in a dose-dependent manner. Cellular growth kinetics showed ranibizumab to be less aggressive, but three other anti-VEGFs showed higher antiproliferative and apoptotic activity and expressed negative cellular growth kinetics. Conclusions. The antiproliferative, apoptotic, and autophagic activity of anti-VEGFs upon fibroblasts may explain the cellular response and the etiology of CNV involution in vivo and serve as a good study model for CNV in vitro.
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- 2015
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68. A Simple Method for Establishing Adherent Ex Vivo Explant Cultures from Human Eye Pathologies for Use in Subsequent Calcium Imaging and Inflammatory Studies
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Sofija Andjelic, Xhevat Lumi, Zoltán Veréb, Natasha Josifovska, Andrea Facskó, Marko Hawlina, and Goran Petrovski
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Immunologic diseases. Allergy ,RC581-607 - Abstract
A novel, simple, and reproducible method for cultivating pathological tissues obtained from human eyes during surgery was developed using viscoelastic material as a tissue adherent to facilitate cell attachment and expansion and calcium imaging of cultured cells challenged by mechanical and acetylcholine (ACh) stimulation as well as inflammatory studies. Anterior lens capsule-lens epithelial cells (aLC-LECs) from cataract surgery and proliferative diabetic retinopathy (PDR) fibrovascular epiretinal membranes (fvERMs) from human eyes were used in the study. We hereby show calcium signaling in aLC-LECs by mechanical and acetylcholine (ACh) stimulation and indicate presence of ACh receptors in these cells. Furthermore, an ex vivo study model was established for measuring the inflammatory response in fvERMs and aLC-LECs upon TNFα treatment.
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- 2014
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69. Effects of Awakening and the Use of Topical Dexamethasone and Levofloxacin on the Cytokine Levels in Tears Following Corneal Transplantation
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Mariann Fodor, Goran Petrovski, Dorottya Pásztor, Péter Gogolák, Éva Rajnavölgyi, and András Berta
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Immunologic diseases. Allergy ,RC581-607 - Abstract
Objectives. To study the short-term effect of eye opening and use of topical dexamethasone phosphate 0.1% and levofloxacin 0.5% on the cytokine levels in human tears. Methods. Prospective experimental design was used for tear collection from eyes of 10 healthy controls and 20 patients four days after penetrating keratoplasty (PKP) at awakening and after instilling dexamethasone or levofloxacin. The concentrations of different cytokines were measured by cytometric bead array. Results. At eye opening, IL-6 levels were higher in the PKP group as compared to the controls. Thirty minutes later, the released levels of IL-10, IL-13, IL-17, IFNγ, and CCL5 increased in controls, while CXCL8 decreased in both control and PKP groups. The release of the cytokines remained stable after 30 mins except for IFNγ, which showed a decrease in the controls following levofloxacin instillation. No short-term effects of the topically used dexamethasone and levofloxacin could be detected on the cytokine levels in controls and after PKP. Conclusions. Evidence of changes in the levels and time course of tear cytokines after awakening or eye opening could be established and the short-term confounding effects of dexamethasone and levofloxacin on the levels of released cytokines in human tears could be excluded.
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- 2014
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70. Alterations of tear mediators in patients with keratoconus after corneal crosslinking associate with corneal changes.
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Bence Lajos Kolozsvári, András Berta, Goran Petrovski, Kata Miháltz, Péter Gogolák, Eva Rajnavölgyi, Ziad Hassan, Péter Széles, and Mariann Fodor
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Medicine ,Science - Abstract
Keratoconus (KC) is the most common primary corneal ectatic disease which has considerable importance in public health. Corneal collagen crosslinking (CXL) is a procedure to mitigate progression of KC and reduce demand for corneal transplantation. Although studies have proven the efficacy of CXL regarding corneal shape, none have investigated the effects of CXL on tear biomarkers which are useful tools to understand molecular mechanisms behind CXL. Our purpose was to determine the effect of CXL on tear mediators in patients with KC and analyze associations with corneal changes. Tear samples were collected pre-CXL from 26 eyes of 23 patients and during a 12-month follow-up. The mediators' concentration was measured by Cytometric Bead Array technology. Corneal topography parameters measured by Scheimpflug Camera included: Thinnest-corneal-thickness (ThCT), keratometry values (K1, K2), Radii-Minimum (Rmin), Keratoconus-Index (KI), Center-KI (CKI), Index-of-Height Asymmetry (IHA) and Index-of-Surface Variance (ISV). At baseline, KI was correlated negatively with chemokine (C-C motif) ligand 5 (CCL5) (p=0.015) and matrix metalloproteinase (MMP)-13 (p=0.007). At day 4, interleukin (IL)-6 and IL-8 increased, while IL-13, IL-17A, interferon (IFN)-γ, CCL5, MMP-13, epidermal growth factor (EGF), nerve growth factor (NGF) and plasminogen activator inhibitor (PAI-1) decreased significantly compared to pre-CXL concentrations (p≤0.02). At 6 months tissue plasminogen activator (t-PA) increased (p=0.02), while at 12 months Rmin increased (p≤0.004), and IL-6 and CXCL8 (p=0.005 and p=0.047) as well as K1, ISV and KI decreased. After 6 months CKI and ISV showed significant associations with IL-17A; CKI with IL-13 and ThCT with IL-13 (p≤0.02), while at 12 months there were reverse associations between ThCT and IL-6, IL-13, INFγ, CCL5 and PAI-1 (p≤0.02). Alterations of mediators in tear fluid after CXL associate with topographic changes highlight the fact that many mediators are involved in the complex mechanisms after CXL. Further studies on biomarkers to investigate the efficacy of CXL are needed.
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- 2013
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71. Autophagy activation clears ELAVL1/HuR-mediated accumulation of SQSTM1/p62 during proteasomal inhibition in human retinal pigment epithelial cells.
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Johanna Viiri, Marialaura Amadio, Nicoletta Marchesi, Juha M T Hyttinen, Niko Kivinen, Reijo Sironen, Kirsi Rilla, Saeed Akhtar, Alessandro Provenzani, Vito Giuseppe D'Agostino, Stefano Govoni, Alessia Pascale, Hansjurgen Agostini, Goran Petrovski, Antero Salminen, and Kai Kaarniranta
- Subjects
Medicine ,Science - Abstract
Age-related macular degeneration (AMD) is the most common reason of visual impairment in the elderly in the Western countries. The degeneration of retinal pigment epithelial cells (RPE) causes secondarily adverse effects on neural retina leading to visual loss. The aging characteristics of the RPE involve lysosomal accumulation of lipofuscin and extracellular protein aggregates called "drusen". Molecular mechanisms behind protein aggregations are weakly understood. There is intriguing evidence suggesting that protein SQSTM1/p62, together with autophagy, has a role in the pathology of different degenerative diseases. It appears that SQSTM1/p62 is a connecting link between autophagy and proteasome mediated proteolysis, and expressed strongly under the exposure to various oxidative stimuli and proteasomal inhibition. ELAVL1/HuR protein is a post-transcriptional factor, which acts mainly as a positive regulator of gene expression by binding to specific mRNAs whose corresponding proteins are fundamental for key cellular functions. We here show that, under proteasomal inhibitor MG-132, ELAVL1/HuR is up-regulated at both mRNA and protein levels, and that this protein binds and post-transcriptionally regulates SQSTM1/p62 mRNA in ARPE-19 cell line. Furthermore, we observed that proteasomal inhibition caused accumulation of SQSTM1/p62 bound irreversibly to perinuclear protein aggregates. The addition of the AMPK activator AICAR was pro-survival and promoted cleansing by autophagy of the former complex, but not of the ELAVL1/HuR accumulation, indeed suggesting that SQSTM1/p62 is decreased through autophagy-mediated degradation, while ELAVL1/HuR through the proteasomal pathway. Interestingly, when compared to human controls, AMD donor samples show strong SQSTM1/p62 rather than ELAVL1/HuR accumulation in the drusen rich macular area suggesting impaired autophagy in the pathology of AMD.
- Published
- 2013
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72. Nutraceutical with Resveratrol and Omega-3 Fatty Acids Induces Autophagy in ARPE-19 Cells
- Author
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Ali Koskela, Mika Reinisalo, Goran Petrovski, Debasish Sinha, Céline Olmiere, Reijo Karjalainen, and Kai Kaarniranta
- Subjects
autophagy ,p62/SQSTM1 ,LC3 ,proteasome ,resveratrol ,omega-3 ,Nutrition. Foods and food supply ,TX341-641 - Abstract
Impaired autophagic and proteasomal cleansing have been documented in aged retinal pigment epithelial (RPE) cells and age-related macular degeneration (AMD). Omega-3 fatty acids and resveratrol have many positive homeostatic effects in RPE cells. In this work, ARPE-19 cells were treated with 288 ng of Resvega, containing 30 mg of trans resveratrol and 665 mg of omega-3 fatty acids, among other nutrients, with proteasome inhibitor MG-132 or autophagy inhibitor bafilomycin A1 up to 48 h. Autophagy markers p62/SQSTM1 (p62) and LC3 (microtubule-associated protein 1A/1B-light chain 3) were analyzed by Western blotting. Fluorescence microscopy with mCherry-GFP-LC3 plasmid was applied to study the autophagy flux, and cytoprotective effects were investigated with colorimetric MTT and LDH assays. Resvega induced autophagy by showing increased autolysosome formation and autophagy flux, and the change in the p62 and LC3 protein levels further confirmed the fluorescent microscopy results. Moreover, Resvega provided a clear cytoprotection under proteasome inhibition. These findings highlight the potential of the nutraceuticals containing resveratrol, omega-3 fatty acids and other nutrients in the prevention of ARPE-19 cell damage.
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- 2016
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73. Cultivation and characterization of cornea limbal epithelial stem cells on lens capsule in animal material-free medium.
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Réka Albert, Zoltán Veréb, Krisztián Csomós, Morten C Moe, Erik O Johnsen, Ole Kristoffer Olstad, Bjørn Nicolaissen, Eva Rajnavölgyi, László Fésüs, András Berta, and Goran Petrovski
- Subjects
Medicine ,Science - Abstract
A simple, reproducible, animal-material free method for cultivating and characterizing cornea limbal epithelial stem cells (LESCs) on human lens capsule (LC) was developed for future clinical transplantation. The limbal tissue explants (2 × 2 × 0.25 mm) were harvested from 77 cadavers and expanded ex vivo on either cell culture plates or LC in medium containing human serum as the only growth supplement. Cell outgrowth at the edge of the explants was observed within 24 hours of cultivation and achieved viable outgrowth (>97% viability as measured by MTT assay and flow cytometry) within two weeks. The outgrowing cells were examined by genome-wide microarray including markers of stemness (p63α, ABCG2, CK19, Vimentin and Integrin α9), proliferation (Ki-67), limbal epithelial cells (CK 8/18 and 14) and differentiated cornea epithelial cells (CK 3 and 12). Immunostaining revealed the non-hematopoietic, -endothelial and -mesenchymal stem cell phenotype of the LESCs and the localization of specific markers in situ. Cell adhesion molecules, integrins and lectin-based surface carbohydrate profiling showed a specific pattern on these cells, while colony-formation assay confirmed their clonal potency. The LESCs expressed a specific surface marker fingerprint (CD117/c-kit, CXCR4, CD144/VE-Cadherin, CD146/MCAM, CD166/ALCAM, and surface carbohydrates: WGA, ConA, RCA, PNA and AIL) which can be used for better localization of the limbal stem cell niche. In summary, we report a novel method combining the use of a medium with human serum as the only growth supplement with LC for cultivating, characterizing and expanding cornea LESCs from cadavers or alternatively from autologous donors for possible treatment of LESC deficiency.
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- 2012
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74. ATP release from dying autophagic cells and their phagocytosis are crucial for inflammasome activation in macrophages.
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Gizem Ayna, Dmitri V Krysko, Agnieszka Kaczmarek, Goran Petrovski, Peter Vandenabeele, and László Fésüs
- Subjects
Medicine ,Science - Abstract
Pathogen-activated and damage-associated molecular patterns activate the inflammasome in macrophages. We report that mouse macrophages release IL-1β while co-incubated with pro-B (Ba/F3) cells dying, as a result of IL-3 withdrawal, by apoptosis with autophagy, but not when they are co-incubated with living, apoptotic, necrotic or necrostatin-1 treated cells. NALP3-deficient macrophages display reduced IL-1β secretion, which is also inhibited in macrophages deficient in caspase-1 or pre-treated with its inhibitor. This finding demonstrates that the inflammasome is activated during phagocytosis of dying autophagic cells. We show that activation of NALP3 depends on phagocytosis of dying cells, ATP release through pannexin-1 channels of dying autophagic cells, P(2)X(7) purinergic receptor activation, and on consequent potassium efflux. Dying autophagic Ba/F3 cells injected intraperitoneally in mice recruit neutrophils and thereby induce acute inflammation. These findings demonstrate that NALP3 performs key upstream functions in inflammasome activation in mouse macrophages engulfing dying autophagic cells, and that these functions lead to pro-inflammatory responses.
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- 2012
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75. Hand tremor-based hypoglycemia detection and prediction in adolescents with type 1 diabetes.
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Lilia Aljihmani, Oussama Kerdjidj, Goran Petrovski, Madhav Erraguntla, Farzan Sasangohar, Ranjana K. Mehta, and Khalid A. Qaraqe
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- 2022
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76. Wnt/β-Catenin Signaling Activation Induces Differentiation in Human Limbal Epithelial Stem Cells Cultured Ex Vivo
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Noer, Jovana Bisevac, Kirankumar Katta, Goran Petrovski, Morten Carstens Moe, and Agate
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limbal epithelial stem cells ,Wnt/β-catenin signaling ,stemness ,proliferation ,differentiation - Abstract
Human limbal epithelial stem cells (hLESCs) continuously replenish lost or damaged human corneal epithelial cells. The percentage of stem/progenitor cells in autologous ex vivo expanded tissue is essential for the long-term success of transplantation in patients with limbal epithelial stem cell deficiency. However, the molecular processes governing the stemness and differentiation state of hLESCs remain uncertain. Therefore, we sought to explore the impact of canonical Wnt/β-catenin signaling activation on hLESCs by treating ex vivo expanded hLESC cultures with GSK-3 inhibitor LY2090314. Real-time qRT-PCR and microarray data reveal the downregulation of stemness (TP63), progenitor (SOX9), quiescence (CEBPD), and proliferation (MKI67, PCNA) genes and the upregulation of genes for differentiation (CX43, KRT3) in treated- compared to non-treated samples. The pathway activation was shown by AXIN2 upregulation and enhanced levels of accumulated β-catenin. Immunocytochemistry and Western blot confirmed the findings for most of the above-mentioned markers. The Wnt/β-catenin signaling profile demonstrated an upregulation of WNT1, WNT3, WNT5A, WNT6, and WNT11 gene expression and a downregulation for WNT7A and DKK1 in the treated samples. No significant differences were found for WNT2, WNT16B, WIF1, and DKK2 gene expression. Overall, our results demonstrate that activation of Wnt/β-catenin signaling in ex vivo expanded hLESCs governs the cells towards differentiation and reduces proliferation and stem cell maintenance capability.
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- 2023
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77. Ex Vivo Pig Eye Model for Studying Diffusion of Acylcarnitines with Different Physicochemical Properties
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John Kim Hiller, Elise Mørk Sandås, Helge Rootwelt, Anja Østeby Vassli, Tor Paaske Utheim, Morten Carstens Moe, Katja Benedikte Prestø Elgstøen, and Goran Petrovski
- Subjects
Pharmacology ,Ophthalmology ,Pharmacology (medical) - Published
- 2023
78. Macular hole Delphi consensus statement (MHOST)
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Filippo Confalonieri, Hanna Haave, Susanne Binder, Agnieszka Monika Bober, Ragnheidur Bragadottir, Thomas Bærland, Rowan Faber, Vegard Forsaa, Julio J. Gonzalez‐Lopez, Andrea Govetto, Marta Haugstad, Domagoj Ivastinovic, Neža Čokl Jenko, Simona Delia Nicoară, Kuldar Kaljurand, Igor Kozak, Anders Kvanta, Lyubomyr Lytvynchuk, Zofia Anna Nawrocka, Sanja Petrovic Pajic, Mojca Globočnik Petrovič, Liga Radecka, Matus Rehak, Mario R. Romano, Andrii Ruban, Martynas Speckauskas, Ingar Stene‐Johansen, Zbynek Stranak, Angela Thaler, Anna Sophie Aagaard Thein, Ioannis Theocharis, Zoran Tomic, Xiaohe Yan, Muhamet Zekolli, Burim Zhuri, Ljubo Znaor, Beata Eva Petrovski, Miriam Kolko, Xhevat Lumi, and Goran Petrovski
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Ophthalmology ,General Medicine - Published
- 2023
79. Intracorneal Implantation of 3D Bioprinted Scaffolds Containing Mesenchymal Stromal Cells Using Femtosecond‐Laser‐Assisted Intrastromal Keratoplasty
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Gerard Boix‐Lemonche, Richard M. Nagymihaly, Essi M. Niemi, Natasha Josifovska, Stian Johansen, Morten C. Moe, Hanne Scholz, and Goran Petrovski
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Biomaterials ,Polymers and Plastics ,Materials Chemistry ,Bioengineering ,Biotechnology - Published
- 2023
80. Comments on: Internal Limiting Membrane Peeling and Gas Tamponade for Full-Thickness Macular Holes of Different Etiology – Is It Still Relevant? [Response to Letter]
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Andrii Ruban, Beáta Éva Petrovski, Goran Petrovski, and Lyubomyr M Lytvynchuk
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Ophthalmology ,Clinical Ophthalmology - Abstract
Andrii Ruban,1 Beáta Éva Petrovski,2 Goran Petrovski,2–4 Lyubomyr M Lytvynchuk5,6 1Center of Clinical Ophthalmology, Kyiv, Ukraine; 2Department of Ophthalmology, Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway; 3Center for Eye Research, Department of Ophthalmology, Oslo University Hospital, Oslo, Norway; 4Department of Ophthalmology, University of Split School of Medicine and University Hospital Centre, Split, Croatia; 5Department of Ophthalmology, Justus-Liebig- University Giessen, Eye Clinic, University Hospital Giessen and Marburg GmbH, Giessen, Germany; 6Karl Landsteiner Institute for Retinal Research and Imaging, Vienna, AustriaCorrespondence: Lyubomyr M Lytvynchuk, Department of Ophthalmology, Justus-Liebig-University Giessen, Eye Clinic, University Hospital Giessen and Marburg GmbH, Campus Giessen, Friedrichstrasse 18, Giessen, 35392, Germany, Tel +49 64198543820, Fax +49 64198543809, Email Lyubomyr.Lytvynchuk@augen.med.uni-giessen.de
- Published
- 2023
81. Laser Treatment of Submacular Hemorrhages
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Lyubomyr Lytvynchuk, Stanislav Saksonov, Goran Petrovski, and Andrzej Grzybowski
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- 2023
82. Laser in Treatment of Retinal Artery Occlusions
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Stanislav Saksonov, Lyubomyr Lytvynchuk, Goran Petrovski, and Andrzej Grzybowski
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- 2023
83. Epidemiology, genetic landscape and classification of childhood diabetes mellitus in the State of Qatar
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Noor Hamed, Fawziya Al-Khalaf, Sara Al-Khawaga, Khalid Hussain, Tasneem Abdel-Karim, Goran Petrovski, Sabri Boughorbel, Reem Hasnah, Amira Saeed, Houda Afyouni, Shihab Mundekkadan, Ahmed Elawwa, Basma Haris, Maryam Al-Maadheed, Amel Khalifa, Saras Saraswathi, Mahmoud Alzyoud, Shayma Mohammed, and Ahmed Shamekh
- Subjects
Male ,medicine.medical_specialty ,Pediatrics ,Adolescent ,endocrine system diseases ,Epidemiology ,Endocrinology, Diabetes and Metabolism ,Type 2 diabetes ,Maturity onset diabetes of the young ,Diseases of the endocrine glands. Clinical endocrinology ,Neonatal diabetes mellitus ,Diabetes mellitus ,Prevalence ,Internal Medicine ,medicine ,Humans ,Childhood Diabetes Mellitus ,Prospective Studies ,Child ,Qatar ,Type 1 diabetes ,business.industry ,Incidence ,Incidence (epidemiology) ,Infant, Newborn ,Infant ,Articles ,General Medicine ,medicine.disease ,RC648-665 ,Diabetes Mellitus, Type 1 ,Diabetes Mellitus, Type 2 ,Child, Preschool ,Original Article ,Female ,business ,Pediatric diabetes - Abstract
Aims/Introduction To study the epidemiology, genetic landscape and causes of childhood diabetes mellitus in the State of Qatar. Materials and methods All patients (aged 0–18 years) with diabetes mellitus underwent biochemical, immunological and genetic testing. American Diabetes Association guidelines were used to classify types of diabetes mellitus. The incidence and prevalence of all the different types of diabetes mellitus were calculated. Results Total number of children with diabetes mellitus was 1,325 (type 1 n = 1,096, ≥1 antibody; type 2 n = 104, type 1B n = 53; maturity onset diabetes of the young n = 20; monogenic autoimmune n = 4; neonatal diabetes mellitus n = 10;, syndromic diabetes mellitus n = 23; and double diabetes mellitus n = 15). The incidence and prevalence of type 1 diabetes were 38.05 and 249.73 per 100,000, respectively, and for type 2 were 2.51 and 23.7 per 100,000, respectively. The incidence of neonatal diabetes mellitus was 34.4 per 1,000,000 live births, and in indigenous Qataris the incidence was 43.6 per 1,000,000 live births. The prevalence of type 1 diabetes and type 2 diabetes in Qatari children was double compared with other nationalities. The prevalence of maturity onset diabetes of the young in Qatar was 4.56 per 100,000. Conclusions This is the first prospective and comprehensive study to document the epidemiology and genetic landscape of childhood diabetes mellitus in this region. Qatar has the fourth highest incidence of type 1 diabetes mellitus, with the incidence and prevalence being higher in Qatari compared with non‐Qatari. The prevalence of type 2 diabetes mellitus is also higher in Qatar than in Western countries. The incidence of neonatal diabetes mellitus is the second highest in the world. GCK is the most common form of maturity onset diabetes of the young, and a large number of patients have type 1B diabetes mellitus., This is the first comprehensive, prospective study from the Middle East North Africa region to systematically study the causes of diabetes in every child in the State of Qatar. The State of Qatar has the fourth highest incidence of type 1 diabetes in the world. The incidence of type 2 diabetes is much higher in Qatar than in Western countries. Both type 1 and type 2 diabetes are more common in the Qatari population than the non‐Qatari population. Mutations in GCK were the most common cause of maturity onset diabetes of the young, and mutations in the PTF1A and INS genes were the most common cause of neonatal diabetes in this population.
- Published
- 2021
84. Synchrotron‐based <scp>FTIR</scp> microspectroscopy of human primary retinal pigmented epithelial cells as a model for age‐related macular degeneration
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Natasha Josifovska, Sofija Andjelic, Xhevat Lumi, Tanja Ducic, and Goran Petrovski
- Subjects
Ophthalmology ,General Medicine - Published
- 2022
85. Morphological changes of eye tissues after the influence of high‐frequency electric current welding with suprachoroidal approach to induce chorio‐retinal adhesion
- Author
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Omar Saoud, Andrii Sergiienko, Anatoliy Korol, Mykola Umanets, Goran Petrovski, Matus Rehak, and Lyubomyr Lytvynchuk
- Subjects
Ophthalmology ,General Medicine - Published
- 2022
86. Intra‐corneal implantation of <scp>3D</scp> bio‐printed mesenchymal stem cells using femtosecond‐laser‐ assisted intrastromal keratoplasty
- Author
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Gerard Boix Lemonche, Richard M. Nagymihaly M. Nagymihaly, Essi M. Niemi, Natasha Josifovska, Stian Johansen, Morten Carstens Moe, Hanne Scholz, and Goran Petrovski
- Subjects
Ophthalmology ,General Medicine - Published
- 2022
87. Genetic variability of inflammation and oxidative stress genes in retinal detachment patients with and without proliferative vitreoretinopathy
- Author
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Xhevat Lumi, Filippo Confalonieri, Metka Ravnik‐Glavač, Katja Goričar, Tanja Blagus, Vita Dolžan, Goran Petrovski, Marko Hawlina, and Damjan Glavač
- Subjects
Ophthalmology ,General Medicine - Published
- 2022
88. Animal model for metabolomic diffusion studies in the eye
- Author
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John Kim Hiller, Elise Mørk Sandås, Helge Rootwelt, Anja Østeby Vassli, Tor Paaske Utheim, Morten Carstens Moe, Katja Benedikte Prestø Elgstøen, and Goran Petrovski
- Subjects
Ophthalmology ,General Medicine - Published
- 2022
89. A novel technique of amniotic membrane suturing for ex vivo cultivated limbal epithelial stem cell expansion increases the number of progenitor cells
- Author
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Jovana Bisevac, Morten Carstens Moe, Goran Petrovski, and Agate Noer
- Subjects
Ophthalmology ,General Medicine - Published
- 2022
90. Nanofibrous scaffolds with ex vivo cultured human <scp>iPSC</scp> ‐derived <scp>RPE</scp> cells for transplantation into porcine eyes
- Author
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Taras Ardan, Slaven Erceg, Ana Artero‐Castro, Hana Studenovská, Brigitte Mueller, Knut Stieger, Štěpan Popelka, Lyubomyr Lytvynchuk, Zbyněk Straňák, Lucie Tichotová, Zdeňka Ellederová, Jana Čížková, Jana Juhásová, Jan Motlík, and Goran Petrovski
- Subjects
Ophthalmology ,General Medicine - Published
- 2022
91. clinical grade of genetically corrected <scp>RPE</scp> cells for autologous cell therapy of hereditary retinal dystrophies
- Author
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Juan Ureña‐Peralta, Anna Brymova, Noelia Pimentel Mayordomo, Pavla Jendelova, Taras Ardan, Hana Studenovska, Jan Motlik, Goran Petrovski, and Slaven Erceg
- Subjects
Ophthalmology ,General Medicine - Published
- 2022
92. The prevalence, immune profile, and clinical characteristics of children with celiac disease and type 1 diabetes mellitus in the state of Qatar
- Author
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Ahmed Elawwa, Maryam Al-Maadheed, Tasneem Abdel-Karim, Basma Haris, Ahmed Abdellatief, Goran Petrovski, Shayma Mohammed, Mahmoud Al Zyoud, Amel Khalifa, Khalid Hussain, Fawziya Al-Khalaf, and Houda Afyouni
- Subjects
Male ,medicine.medical_specialty ,Adolescent ,Endocrinology, Diabetes and Metabolism ,Population ,Disease ,Human leukocyte antigen ,Asymptomatic ,Endocrinology ,Internal medicine ,Diabetes mellitus ,Prevalence ,medicine ,Humans ,Family history ,Child ,education ,Qatar ,Autoantibodies ,education.field_of_study ,Type 1 diabetes ,Glutamate Decarboxylase ,business.industry ,Infant, Newborn ,Infant ,medicine.disease ,Celiac Disease ,Diabetes Mellitus, Type 1 ,Child, Preschool ,Pediatrics, Perinatology and Child Health ,Female ,medicine.symptom ,Age of onset ,business - Abstract
Objectives Children with antibody positive type 1 diabetes mellitus (type 1 diabetes) are at an increased risk of developing celiac disease (CD) which suggests a common autoimmune basis with both high-risk human lymphocyte antigen (HLA) and non-HLA factors playing a role in the pathophysiology. We aim to describe the prevalence, immune profile, and clinical characteristics of children with CD who have type 1 diabetes mellitus in Qatar. Methods All children (aged 0–18 years) attending a regional diabetes clinic with antibody positive type 1 diabetes were screened for CD. Measurement of tissue transglutaminase IgA and IgG as well as anti-endomysial antibody, was done, clinical details about the birth history, family history of diabetes and CD, age of onset, and ethnicity were collected. Results Out of the 1,325 children with antibody positive type 1 diabetes, 54 were identified to have CD on screening and then confirmed on small bowel biopsy. The prevalence of CD in the type 1 diabetes childhood population in Qatar is 4.07%. CD and type 1 diabetes were more prevalent in the Qatari children (n=32) as compared to non-Qatari (n=22) and occurred mostly in the age group 6–10 years. The most common type 1 diabetes antibodies in children with CD were glutamic acid decarboxylase and insulin autoantibody. Twelve subjects were asymptomatic for CD symptoms and picked up only on screening. Conclusions The prevalence of CD in children with type 1 diabetes in Qatar is comparable to reports from around the world. Many children were asymptomatic and thus routine screening is recommended.
- Published
- 2021
93. Benzalkonium Chloride-Preserved Anti-Glaucomatous Eye Drops and Their Effect on Human Conjunctival Goblet Cells in vitro
- Author
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Xenia Begun, Barbara Cvenkel, Miriam Kolko, Jeffrey Bair, Rupali Vohra, Goran Petrovski, Zaynab Ahmad Mouhammad, Darlene A. Dartt, Olivia Müllertz, Steffen Heegaard, and Anne Hedengran
- Subjects
Intraocular pressure ,Goblet cell ,Medicine (General) ,in vitro study ,goblet cells ,benzalkonium chloride ,Andrology ,Benzalkonium chloride ,chemistry.chemical_compound ,medicine.anatomical_structure ,glaucoma ,R5-920 ,chemistry ,Brimonidine Tartrate ,Dorzolamide ,Lactate dehydrogenase ,medicine ,General Earth and Planetary Sciences ,Viability assay ,Latanoprost ,biological phenomena, cell phenomena, and immunity ,anti-glaucomatous treatment ,Research Article ,General Environmental Science ,medicine.drug - Abstract
Introduction: Most intraocular pressure (IOP)-lowering eye drops are preserved with benzalkonium chloride (BAK). This can increase side effects and decrease adherence. Particularly, damage to the mucin-producing conjunctival goblet cells may be an issue due to instability of the tear film. We aimed to investigate the effect of IOP-lowering eye drops preserved with BAK on cultured human conjunctival goblet cells. Methods: Eye drops Brimonidine Tartrate Teva (BT) with 0.005% BAK, Dorzolamide Stada (DS) with 0.0075% BAK, Optimol® (OP) with 0.01% BAK, and Latanoprost Teva (LT) with 0.02% BAK were included. Human primary cultured goblet cell survival was evaluated using a lactate dehydrogenase assay on human goblet cells after treatment for 30 min and 6 h with the different anti-glaucoma drug formulations. Results: All eye drops examined, except BT, reduced goblet cell survival. The impact of eye drops on goblet cell viability was correlated with the time of exposure as well as to the concentration of BAK. After 30 min of exposure, cell viability was 93% for BT (0.005% BAK; p = 0.93), 71% for DS (0.0075% BAK; p = 0.067), 70% for OP (0.01% BAK; p = 0.054), and 69% for LT (0.02% BAK; p = 0.022), and exposure for 6 h reduced cell survival to 74% for BT (p = 0.217), 52% for DS (p = 0.011), 34% for OP (p = 0.017), and 31% for LT (p = 0.0007). Conclusion: LT, OP, and DS reduced human goblet cell survival in a time-dependent manner. BT did not affect goblet cell survival. Cell survival was correlated with the BAK concentration in the eye drops making 0.02% BAK-preserved LT most toxic and 0.005% BAK-preserved BT least toxic. Based on the present study, decreasing BAK in eye drops for chronic use seems important to reduce damage to the goblet cells. However, future studies are needed to further explore this finding.
- Published
- 2021
94. Iris Racemose Hemangioma Assessment with Swept Source Optical Coherence Tomography Angiography: A Feasibility Study and Stand-Alone Comparison
- Author
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Filippo Confalonieri, Huy Bao Ngo, Helga Halldorsdottir Petersen, Nils Andreas Eide, and Goran Petrovski
- Subjects
iris racemose hemangioma ,iris arteriovenous malformation ,iris arteriovenous aneurysm ,Swept Source Optical Coherence Tomography (SS-OCT) ,OCT angiography (OCTA) ,General Medicine - Abstract
Purpose: To evaluate arteriovenous malformations (AVM) with swept-source (SS) optical coherence tomography (OCT) angiography (OCTA) in iris racemose hemangioma and compare it with traditional intravenous iris fluorescein angiography (IVFA). Methods: A cross-sectional observational clinical study was conducted on patients with iris racemose hemangioma with the ZEISS PLEX Elite 9000 SS OCT & OCTA. Results: Three eyes of three patients were imaged. Iris racemose hemangiomas demonstrated a tortuous, well-defined, and continuous course of the AVM. The ZEISS PLEX Elite 9000 SS OCT & OCTA allowed for a detailed visualization of the ARM and was superior to IVFA in depicting small caliber, fine vessels. Conclusions: SS-OCTA may provide a dye-free, no-injection, cost-effective method comparable to spectral domain OCTA and IVFA for diagnosing and monitoring iris racemose hemangiomas for growth and vascularity.
- Published
- 2022
95. Adverse effects and Safety in Glaucoma Patients - Agreement on Clinical Trial Outcomes for Reports on Eye Drops (ASGARD) - A Delphi Consensus Statement
- Author
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Anna-Sophie Thein, Anne Hedengran, Augusto Azuara-Blanco, Reiko Arita, Barbara Cvenkel, Gus Gazzard, Steffen Heegaard, Cintia S. de Paiva, Goran Petrovski, Verena Prokosch-Willing, Tor P. Utheim, Gianni Virgili, and Miriam Kolko
- Subjects
Ophthalmology ,Consensus ,ocular surface ,Delphi Technique ,Drug-Related Side Effects and Adverse Reactions ,consensus ,Surveys and Questionnaires ,Quality of Life ,adverse effects ,Humans ,Glaucoma ,Ophthalmic Solutions ,Delphi Study - Abstract
Purpose: The purpose of this study is to establish consensus among experts on outcomes and methods to be used in clinical trials to assess adverse effects of anti-glaucomatous eye drops. Design: Modified Delphi method. Methods: Clinical experts from Europe, North America, South America, the Middle East, and Asia were invited to participate in two sequential web-based surveys administered from June 27 to August 29, 2021. A total of 91 clinical experts were invited to participate. Of these, 71 (78%) experts from 23 different countries accepted the invitation and answered the first questionnaire. The importance of items was ranked using a 10-point scale (1 as not important, 10 as very important). Results: A total of 84 items were rated in round one by 71 participants. Of these, 68 (81%) reached consensus. In round two, 19 items, including three additional items, were rated by 53 (75%) participants. Consensus was reached in 98% of investigated items. Eight outcomes were agreed as important to assess when conducting future trials: ocular surface, dryness, epithelial damage, local adverse effects related to eye drops as reported by patients, periocular surroundings and eyelids, quality of life questionnaires, hyperemia, visual acuity, tear film, and anterior chamber inflammation. Conclusion: We propose a consensus-based series of outcomes and assessment methods to be used in clinical trials assessing adverse effects of anti-glaucomatous eye drops. This will hopefully improve the comparability of results from future trials and thus facilitate meta-analyses and progress in this field.
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- 2022
96. Simplified Meal Announcement Versus Precise Carbohydrate Counting in Adolescents With Type 1 Diabetes Using the MiniMed 780G Advanced Hybrid Closed Loop System: A Randomized Controlled Trial Comparing Glucose Control
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Goran Petrovski, Judith Campbell, Maheen Pasha, Emma Day, Khalid Hussain, Amel Khalifa, and Tim van den Heuvel
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Advanced and Specialized Nursing ,Endocrinology, Diabetes and Metabolism ,Internal Medicine - Abstract
OBJECTIVEWe aimed to compare glucose control in adolescents with type 1 diabetes (T1D) using the MiniMed 780G system who used simplified meal announcement with those who used precise carbohydrate counting.RESEARCH DESIGN AND METHODSThis randomized controlled trial included 34 participants (age 12–18 years) with T1D who were on multiple daily injections or insulin pump and were scheduled to start using the MiniMed 780G system at Sidra Medicine in Qatar. After a 7-day run-in period, participants were randomly assigned to the fix group (simplified meal announcement by preset of three personalized fixed carbohydrate amounts) or the flex group (precise carbohydrate counting) and followed for 12 weeks. Between-group difference in time in range (TIR) was the primary end point. Secondary end points included HbA1c and other glycometrics.RESULTSDuring the 12-week study phase, TIR was 73.5 ± 6.7% in the fix and 80.3 ± 7.4% in the flex group, with a between-group difference of 6.8% in favor of flex (P = 0.043). Time >250 mg/dL was better in the flex group (P = 0.012), whereas HbA1c (P = 0.168), time below range (P = 0.283), and time between 180 and 250 mg/dL (P = 0.114) did not differ.CONCLUSIONSAdolescents using the MiniMed 780G system with a preset of three personalized fixed carbohydrate amounts can reach international targets of glycemic control. Therefore, it may be a valuable alternative to precise carbohydrate counting in users who are challenged by precise carbohydrate counting. Because carbohydrate counting further improves outcomes, these skills remain important for MiniMed 780G users.
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- 2022
97. The acute phase response protein SERPINA3 is increased in tear fluid from the unaffected eyes of patients with unilateral acute anterior uveitis
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Øystein Kalsnes Jørstad, Goran Petrovski, Ole Kristoffer Olstad, Maja Akopian, Jon Roger Eidet, Milaim Pepaj, and Morten C. Moe
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Proteomics ,medicine.medical_specialty ,medicine.drug_class ,Uveitis ,03 medical and health sciences ,0302 clinical medicine ,Ophthalmology ,medicine ,In patient ,Original Research ,business.industry ,Acute-phase protein ,Biomarker ,RE1-994 ,medicine.disease ,Androgen ,Tear fluid ,eye diseases ,ACUTE ANTERIOR UVEITIS ,Infectious Diseases ,Potential biomarkers ,030221 ophthalmology & optometry ,Biomarker (medicine) ,Population study ,sense organs ,business ,030215 immunology - Abstract
Background To identify candidate tear fluid biomarkers in patients with unilateral acute anterior uveitis (AAU) that can aid in the differentiation between these patients and patients with bacterial keratitis or healthy controls. Methods Thirteen patients (40.1 ± 16.2 years of age) with unilateral AAU, seven patients with unilateral bacterial keratitis (40.2 ± 15.3 years of age), and 14 healthy subjects (41.1 ± 11.6 years of age) were included. The tear proteome of affected eyes was compared with that of the unaffected eye or healthy controls. Proteins were identified by liquid chromatography tandem mass spectrometry and enzyme-linked immunosorbent assay. Results Relative protein ratios were detected and calculated for 272 unique proteins. Compared with healthy controls and the unaffected eye, the top upregulated proteins in AAU eyes were submaxillary gland androgen regulated protein 3B (SMR3B) and SMR3A. Similarly, the top upregulated proteins in bacterial keratitis were S100 calcium-binding protein A9 and orosomucoid 2. The acute phase response protein Serpin Family A Member 3 (SERPINA3) was increased in the healthy eye of AAU patients (P = 0.019) compared with healthy controls. Laser flare measurements in affected eyes of AAU patients showed positive logarithmic correlation with SERPINA3 in tear samples of the unaffected eye (P = 0.022). The use of SERPINA3 as a tear biomarker yielded a sensitivity of 85% and a specificity of 71% in detecting patients with AAU in the study population. Conclusions The acute phase response protein SERPINA3 was increased in tear samples of unaffected eyes of patients with unilateral AAU compared with healthy controls. This study highlights SERPINA3 as a potential biomarker for AAU. Future research should explore the dynamic properties of SERPINA3 in the tear fluid of active and quiescent uveitis eyes.
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- 2021
98. Corectopia grading: A novel classification system
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Goran Petrovski, S. I. Anisimov, Argyrios Tzamalis, Lisa B. Arbisser, Boris Malyugin, Natalya F. Shilova, Natalia S. Anisimova, and Beáta Éva Petrovski
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Observer Variation ,medicine.medical_specialty ,genetic structures ,Corectopia ,business.industry ,Intraclass correlation ,Reproducibility of Results ,Pupil ,General Medicine ,eye diseases ,Confidence interval ,03 medical and health sciences ,Ophthalmology ,0302 clinical medicine ,Pupil Disorders ,030221 ophthalmology & optometry ,medicine ,Mydriasis ,Humans ,medicine.symptom ,Grading (education) ,business ,030217 neurology & neurosurgery - Abstract
Objectives: To present and validate the novel grading system for objective classification of corectopia.Subjects and Methods: We evaluated 28 eyes of 28 patients with or without corectopia and validated the grading and classification system for corectopia according to three major criteria: (i) direction, (ii) extent, and (iii) alteration of mydriasis. Intraclass correlation coefficient (ICC) and inter-rater agreement between 7 inexperienced and 1 experienced ophthalmologist against a golden standard (GS) were calculated.Results: The ICC for the 7 inexperienced ophthalmologists regarding the grading of direction and centration of the pupil was 0.83 (95% confidence interval (CI), 0.74 to 0.90; p
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- 2021
99. 785-P: Comparison of Six Months Experience on Hybrid Closed Loop MiniMed 670G System and Advanced Hybrid Closed Loop MiniMed 780G System Using a Structured Initiation Protocol in Children and Adolescents with Type 1 Diabetes
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GORAN PETROVSKI, JUDITH CAMPBELL, FAWZIYA ALKHALAF, and KHALID HUSSAIN
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Endocrinology, Diabetes and Metabolism ,Internal Medicine - Abstract
Background: The objective of this study was to evaluate glycemic outcomes using a structured initiation protocol for Hybrid Closed Loop (HCL) MiniMed 670G and Advanced Hybrid Closed Loop (AHCL) Minimed 780G system in children and adolescents with Type 1 Diabetes (T1D) previously treated with Multiple Daily Injections. Methods: The data from two separate (HCL and AHCL system) investigations were analyzed in individuals (aged 7-18 years) with T1D on MDI therapy, both followed a structured initiation protocol. Time in Ranges, HbA1c and system characteristics were analyzed between two systems at 3 and 6 months of Automated Insulin Delivery (AID) . Results: 30 children (age 10.24 ± 2.6 years, HbA1c 8.2±1.4% (66±15.3 mmol/mol)) with HCL system and 34 children (12.5 ± 3.7 years, 8.6±1.7% (70±18.6 mmol/mol)) with AHCL system completed the planned 12 weeks of AID. TIR (70-180mg/dl) of 73.4±8.9% with HCL and 78.2±4.3% with AHCL (p=0.01) was achieved at 6 months of AID. No episodes of severe hypoglycemia or DKA were reported using both systems. Conclusion: Individuals using AHCL MiniMed 780G system had more stringent system settings, spent more time in AID with less exits, which possibly lead to further improvements of glycemic control compared to HCL MiniMed 670G system using the same structured protocol. Disclosure G.Petrovski: None. J.Campbell: Advisory Panel; Medtronic. F.Alkhalaf: None. K.Hussain: None.
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- 2022
100. Internal Limiting Membrane Peeling and Gas Tamponade For Full-Thickness Macular Holes of Different Etiology - Is It Still Relevant?
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Andrii Ruban, Beáta Éva Petrovski, Goran Petrovski, and Lyubomyr M Lytvynchuk
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Ophthalmology ,full-thickness macular hole, pars plana vitrectomy, internal limiting membrane peeling, gas tamponade, restoration of ELM/EZ, macular hole closure ,Clinical Ophthalmology - Abstract
Andrii Ruban,1 Beáta Éva Petrovski,2 Goran Petrovski,2– 4 Lyubomyr M Lytvynchuk5,6 1Center of Clinical Ophthalmology, Kyiv, Ukraine; 2Department of Ophthalmology, Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway; 3Center for Eye Research, Department of Ophthalmology, Oslo University Hospital, Oslo, Norway; 4Department of Ophthalmology, University of Split School of Medicine and University Hospital Centre, Split, Croatia; 5Department of Ophthalmology, Justus-Liebig-University Giessen, Eye Clinic, University Hospital Giessen and Marburg GmbH, Giessen, Germany; 6Karl Landsteiner Institute for Retinal Research and Imaging, Vienna, AustriaCorrespondence: Lyubomyr M Lytvynchuk, Department of Ophthalmology, Justus-Liebig-University Giessen, Eye Clinic, University Hospital Giessen and Marburg GmbH, Campus Giessen, Friedrichstrasse 18, Giessen, 35392, Germany, Tel +49 64198543820, Fax +49 64198543809, Email Lyubomyr.Lytvynchuk@augen.med.uni-giessen.deBackground: Despite the abundance of novel surgical approaches proposed for full thickness macular hole (FTMH) treatment, the choice of the optimal technique remains debatable Vitrectomy with «classic» internal limiting membrane peeling and gas tamponade remains the standard of FTMH surgery in many cases, but there are still very limited recent publications on the outcomes of such surgery.Purpose: To investigate the anatomical and functional result and to analyze the significance of outcome-related risk factors of the classic 25-gauge pars plana vitrectomy (PPV) with ILM peeling and gas tamponade (GT) for treatment of FTMH of different etiology.Patients and methods: Thirty-eight eyes of thirty-seven patients with FTMH who underwent 25-gauge PPV, ILM peeling and GT were recruited for this retrospective, consecutive, interventional study. Four eyes with persistent holes underwent a re-operation. Outcome-related factors were discussed.Results: The primary closure rate was 89.5% (34/38). All eyes that underwent the repeated surgery (4 cases) obtained final closure. A hole size of > 500 μm has a statistically significant effect on the primary macular hole closure (F = 0.048; &phis; = 0.38; p Ë 0.05). In the general group (N = 38), the duration of symptoms directly correlated with age (ρ = 0.34; p = 0.04), size of the hole (ρ = 0.66; p Ë 0.001) and BCVA before surgery (ρ = 0.59; p Ë 0.001), after 1 month (ρ = 0.36; p = 0.03), and after 3 months (ρ = 0.35; p = 0.03). Preoperative BCVA was better in initially closed cases (Group 1) (U= 26.0; p = 0.05). In the Group 2 with primary unclosed holes, 75% of the eyes (3/4) had an axial length (AL) > 26 mm, while in Group 1 such eyes were 12.5 times less (2/34) 5.9% (F = 0.004; &phis; = 0.63; Ñ Ë 0.01). The ELM recovery rate at 3 months was 92% (35/38 eyes) and the restoration of EZ at 3 months was 47% (18/38 eyes). Best-corrected visual acuity of all individuals improved significantly from 0.72 ± 0.35 (logMAR) (Me = 0.7; IQR: 0.5– 0.8) to 0.25± 0.14 (logMAR) (Me= 0.2; IQR: 0.2 – 0.3) at 1 month and 0.17 ± 0.13 (logMAR) (Me= 0.2; IQR: 0.1 – 0.2) at 3 months after surgery (P = 0.0001).Conclusion: 25G PPV with ILM and GT for FTMH of different etiology provide satisfactory morphologic and functional outcomes. Elongated AL, large diameter of MH and long duration of symptoms are the risk factors for initial closure. Proper second surgery can obtain satisfactory outcomes for persistent holes.Keywords: full-thickness macular hole, pars plana vitrectomy, internal limiting membrane peeling, gas tamponade, restoration of ELM/EZ, macular hole closure
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- 2022
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