scholarly journals Retinal Vascular Response to Hyperoxia in Patients with Diabetes Mellitus without Diabetic Retinopathy

2021 ◽  
Vol 2021 ◽  
pp. 1-6
Author(s):  
Hamid Safi ◽  
Ramin Nourinia ◽  
Sare Safi ◽  
Ehsan Hadian ◽  
Bahareh Kheiri ◽  
...  
Keyword(s):  
Diabetic Retinopathy ◽  
Healthy Subjects ◽  
Statistical Significance ◽  
Normal Subjects ◽  
Study Groups ◽  
Flow Index ◽  
Vascular Response ◽  
Outer Retina ◽  
Patients With Diabetes ◽  
Capillary Plexus

Purpose. To evaluate the retinal vascular response to hyperoxia in patients with diabetes at the preclinical stage of diabetic retinopathy (DR) and to quantify the changes in comparison with normal subjects using optical coherence tomography angiography (OCTA). Methods. In this prospective study, 40 eyes of 20 participants comprising 10 diabetic patients with no diabetic retinopathy (NDR) and 10 normal subjects were recruited. OCTA images were acquired in the resting position and were repeated after a hyperoxic challenge using a nasal mask connected to a reservoir bag supplying 100% oxygen at the rate of 15 L per minute for 5 minutes. The changes of mean parafoveal vessel density (VD) in the superficial capillary plexus (SCP) and deep capillary plexus (DCP), the foveal avascular zone (FAZ) size, and the outer retina flow index were compared between two conditions in each group and between the two study groups. The statistical significance of differences in the means was evaluated using Student’s t-test for unpaired samples with consideration of the generalized estimating equations (GEE) for intereye correlation. Results. At baseline, the mean parafoveal VD of SCP and DCP were significantly lower in the NDR participants compared to the healthy subjects (P < 0.001 and P = 0.006, respectively). After induction of the hyperoxic challenge in healthy participants, mean parafoveal VD reduced at both the SCP and DCP, but reached a statistical significance only in DCP (P = 0.006). However, following induction of hyperoxic challenge in patients with NDR, no significant decline was noticed in mean parafoveal VD of SCP and DCP. The degree of change in mean parafoveal VD of DCP was statistically significantly more pronounced in healthy subjects compared to the NDR group (P = 0.034). The change in FAZ size and the outer retina flow index were comparable between the two study groups. Conclusion. Retinal capillary layers responded differently to hyperoxia-induced challenge, and in normal subjects, the autoregulatory mechanism was mostly effective in the parafoveal DCP. Retinal vascular reactivity was impaired in SCP and DCP at the preclinical stage of DR. OCTA as a noninvasive modality was able to quantify the retinal vascular response to the hyperoxic challenge.

scholarly journals Volume rendered 3D OCTA assessment of macular ischemia in patients with type 1 diabetes and without diabetic retinopathy

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Enrico Borrelli ◽  
Domenico Grosso ◽  
Mariacristina Parravano ◽  
Eliana Costanzo ◽  
Maria Brambati ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Diabetic Retinopathy ◽  
Healthy Subjects ◽  
Diabetic Group ◽  
Control Group ◽  
Diabetic Patients ◽  
Vascular Volume ◽  
Patients With Diabetes ◽  
Perfusion Density

AbstractThe aim of this study was to measure macular perfusion in patients with type 1 diabetes and no signs of diabetic retinopathy (DR) using volume rendered three-dimensional (3D) optical coherence tomography angiography (OCTA). We collected data from 35 patients with diabetes and no DR who had OCTA obtained. An additional control group of 35 eyes from 35 healthy subjects was included for comparison. OCTA volume data were processed with a previously presented algorithm in order to obtain the 3D vascular volume and 3D perfusion density. In order to weigh the contribution of different plexuses’ impairment to volume rendered vascular perfusion, OCTA en face images were binarized in order to obtain two-dimensional (2D) perfusion density metrics. Mean ± SD age was 27.2 ± 10.2 years [range 19–64 years] in the diabetic group and 31.0 ± 11.4 years [range 19–61 years] in the control group (p = 0.145). The 3D vascular volume was 0.27 ± 0.05 mm3 in the diabetic group and 0.29 ± 0.04 mm3 in the control group (p = 0.020). The 3D perfusion density was 9.3 ± 1.6% and 10.3 ± 1.6% in diabetic patients and controls, respectively (p = 0.005). Using a 2D visualization, the perfusion density was lower in diabetic patients, but only at the deep vascular complex (DVC) level (38.9 ± 3.7% in diabetes and 41.0 ± 3.1% in controls, p = 0.001), while no differences were detected at the superficial capillary plexus (SCP) level (34.4 ± 3.1% and 34.3 ± 3.8% in the diabetic and healthy subjects, respectively, p = 0.899). In conclusion, eyes without signs of DR of patients with diabetes have a reduced volume rendered macular perfusion compared to control healthy eyes.

scholarly journals Quantitative Evaluation of Vascular Density in Diabetic Retinopathy Subtypes using Optical Coherence Tomography Angiography

2020 ◽  
Author(s):  
Fariba Ghassemi ◽  
Kaveh Fadakar ◽  
Sahar Berijani ◽  
Ameneh Babeli ◽  
Alireza Gholizadeh ◽  
...  
Keyword(s):  
Optical Coherence Tomography ◽  
Diabetic Retinopathy ◽  
Optical Coherence Tomography Angiography ◽  
Normal Subjects ◽  
Vascular Density ◽  
Diabetic Patients ◽  
Multivariate Linear Regression Analysis ◽  
Optical Coherence ◽  
Potential Biomarker ◽  
Capillary Plexus

Abstract Background: To determine the discrepancy between quantitative measurement of retinal and choriocapillaris (CC) vascular density (VD) in diabetic retinopathy (DR) stages using spectral domain optical coherence tomography angiography (SD OCTA) and compare it with normal subjects.Methods: 188 eyes of 97 participants were recruited in this cross-sectional study. Macular OCTA (3x3mm) scan was performed and VD at the level of superficial capillary plexus (SCP), deep capillary plexus (DCP) and CC were measured with the device software.Results: In normal subjects, VD in SCP, DCP, and CC were higher in all subsegments. In retinal VD, all calculated parameters were reduced in the more extreme stages of DR, except for foveal VD of SCP. There was a constant pattern of decrease in VD of CC from normal cases to cases of NDR and NPDR and then a slight increase happened in the PDR stage but never touching the normal quantities. Age, fasting blood sugar, and years of diabetes mellitus were correlated with reduced VD in different segments. Multivariate linear regression analysis showed that best-corrected visual acuity (BCVA) was positively correlated with parafoveal VD at SCP and VD of foveal area at CC. VD of all subfields of macular area except foveal DCP VD showed reduced levels in diabetic macular edema (DME) patients compared to those without DME.Conclusions: The findings of the study endorse retina VD changes as a potential biomarker for DR development before retinopathy becomes clinically evident. It seems that parafoveal VD of SCP and foveal VD of CC are good biomarkers to predict VA in the diabetic patients.

scholarly journals Thermography-based analysis of lower limb vascular response to thermal challenge in patients with diabetes mellitus

2016 ◽  
Vol 15 (1) ◽  
pp. 42-49 ◽  
Author(s):  
D. A. Usanov ◽  
A. V. Skripal ◽  
S. N. Potakhin ◽  
A. A. Sagaidachnyi ◽  
A. V. Fomin ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Peripheral Arterial Disease ◽  
Lower Limb ◽  
Healthy Subjects ◽  
Arterial Disease ◽  
Thermal Impact ◽  
Vascular Response ◽  
Compensation Mechanisms ◽  
Patients With Diabetes ◽  
Peripheral Arterial

The aim of the study - thermography-based analysis of lower limb vascular response to thermal impact in patients with trophic disorders, diabetes mellitus and peripheral atherosclerosis. Materials and methods. Thermal impact was carried out using the heating pad acting for 20 minutes. Control of temperature of back of the feet was performed by thermal imaging camera with a thermal sensitivity of 0.02°C. The study involved a group of 8 subjects without vascular disorders of the lower limbs (controls), and patient group of 8 subjects with trophic disorders due to the progression of diabetes and atherosclerosis (age of 67±8 years). All patients had type 2 diabetes and peripheral arterial disease with different levels and the degree of the main arterial occlusion. Intensity of trophic disorders changed from apical necrosis and trophic ulcers to gangrene of the foot. We calculated spectral amplitude parameters and temperature dynamics. Fourier transform was used to perform spectral analysis of temperature data. Results. Temperature response of limbs in patients with diabetes compared with healthy subjects was characterized by monotonous temperature variation without distinct oscillations; reduction in amplitude of oscillations within endothelial temperature range; relatively high average temperature difference between the left and right foot. In the group of healthy subjects reaction on thermal impact is not strictly two-stage, usually interpretable by theory as primary and secondary vasodilation. Conclusions. Decrease of temperature amplitude of endothelial range registered during thermal impact can be the sign of endothelial dysfunction in patients with diabetes and peripheral arterial disease. Spectral and temperature characteristics of reaction of limbs on thermal impact can be used to assess trophic disorders and compensation mechanisms of regulation of metabolic processes in the group of patients with diabetes mellitus.

scholarly journals Reversed Neurovascular Coupling on Optical Coherence Tomography Angiography Is the Earliest Detectable Abnormality before Clinical Diabetic Retinopathy

2020 ◽  
Vol 9 (11) ◽  
pp. 3523
Author(s):  
Yi Stephanie Zhang ◽  
Ilda Mucollari ◽  
Changyow C. Kwan ◽  
Gianna Dingillo ◽  
Jaspreet Amar ◽  
...  
Keyword(s):  
Optical Coherence Tomography ◽  
Diabetic Retinopathy ◽  
Dark Adaptation ◽  
Optical Coherence Tomography Angiography ◽  
Neurovascular Coupling ◽  
Flow Index ◽  
Optical Coherence ◽  
Significant Difference ◽  
Capillary Plexus ◽  
Healthy Eyes

Diabetic retinopathy (DR) has traditionally been viewed as either a microvasculopathy or a neuropathy, though neurovascular coupling deficits have also been reported and could potentially be the earliest derangement in DR. To better understand neurovascular coupling in the diabetic retina, we investigated retinal hemodynamics by optical coherence tomography angiography (OCTA) in individuals with diabetes mellitus (DM) but without DR (DM no DR) and mild non-proliferative DR (mild NPDR) compared to healthy eyes. Using an experimental design to monitor the capillary responses during transition from dark adaptation to light, we examined 19 healthy, 14 DM no DR and 11 mild NPDR individuals. We found that the only structural vascular abnormality in the DM no DR group was increased superficial capillary plexus (SCP) vessel density (VD) compared to healthy eyes, while mild NPDR eyes showed significant vessel loss in the SCP at baseline. There was no significant difference in inner retinal thickness between the groups. During dark adaptation, the deep capillary plexus (DCP) VD was lower in mild NPDR individuals compared to the other two groups, which may leave the photoreceptors more susceptible to ischemia in the dark. When transitioning from dark to ambient light, both diabetic groups showed a qualitative reversal of VD trends in the SCP and middle capillary plexus (MCP), with significantly decreased SCP at 5 min and increased MCP VD at 50 s compared to healthy eyes, which may impede metabolic supply to the inner retina during light adaptation. Mild NPDR eyes also demonstrated DCP dilation at 50 s and 5 min and decreased adjusted flow index at 5 min in light. Our results show altered neurovascular responses in all three macular vascular plexuses in diabetic subjects in the absence of structural neuronal changes on high resolution imaging, suggesting that neurovascular uncoupling may be a key mechanism in the early pathogenesis of DR, well before the clinical appearance of vascular or neuronal loss.

Deep Capillary Macular Perfusion Indices Obtained with OCT Angiography Correlate with Degree of Nonproliferative Diabetic Retinopathy

2017 ◽  
Vol 27 (6) ◽  
pp. 716-729 ◽  
Author(s):  
Kumar Sambhav ◽  
Khaled K. Abu-Amero ◽  
Kakarla V. Chalam
Keyword(s):  
Optical Coherence Tomography ◽  
Diabetic Retinopathy ◽  
Optical Coherence Tomography Angiography ◽  
Inverse Correlation ◽  
Normal Subjects ◽  
Vessel Density ◽  
Perfusion Index ◽  
Flow Index ◽  
Optical Coherence ◽  
Nonproliferative Diabetic Retinopathy

Purpose To evaluate the integrity of macular and temporomacular vasculature in nonproliferative diabetic retinopathy (NPDR) with noninvasive optical coherence tomography angiography (OCTA) and correlate perfusion indices with degree of NPDR. Methods In this prospective observational cross-sectional study, 102 eyes with newly diagnosed NPDR (mild NPDR, 36; moderate NPDR, 21; severe NPDR, 13; NPDR with diabetic macular edema [DME], 32) underwent OCTA. Sixty eyes of normal subjects served as control. Degree of NPDR (based on Early Treatment Diabetic Retinopathy Study criteria) was confirmed with fluorescein angiography. Automated OCTA/split-spectrum amplitude decorrelation angiography software generated perfusion indices (vessel density and flow index) from images of the retina. The perfusion index of superficial and deep retinal plexuses was obtained in both perifoveal (central 1-3 mm) and parafoveal (3-6 mm) areas. Results Deep plexus parafoveal vessel density was 25.23% (±6.1) in mild NPDR, 20.16% (±6.16) in moderate NPDR, 11.16% (±4.16) in severe NPDR, and 17.91% (±4.42) in NPDR + DME compared to normal subjects (36.93% [±8.1]; (p<0.01). Spearman correlation coefficient (rs) between vessel density and level of NPDR severity in the parafoveal region showed inverse correlation for both superficial (rs -0.87; p = 0.083) and deep (rs -0.96; p = 0.017) plexus. Similarly, when vessel density of the perifoveal region was compared with level of NPDR severity, inverse correlation was noted in both superficial (rs -0.85; p = 0.08) and deep (rs -0.98; p = 0.011) plexus. Conclusions Optical coherence tomography angiography clearly delineated the retinal microcirculation and allowed quantification of vascular perfusion of each layer. As diabetic retinopathy progressed, a decrease in perfusion index is more pronounced in the deep retinal plexus and precedes changes in superficial plexus.

scholarly journals Superoxide Dismutase Levels and Polymorphism (Ala16val) In Tuberculosis Patients with Diabetes Mellitus in Medan City

2019 ◽  
Vol 7 (5) ◽  
pp. 730-735 ◽  
Author(s):  
Mutiara Indah Sari ◽  
Milahayati Daulay ◽  
Dian Dwi Wahyuni
Keyword(s):  
Oxidative Stress ◽  
Diabetes Mellitus ◽  
Superoxide Dismutase ◽  
Gene Polymorphism ◽  
Healthy Subjects ◽  
Statistical Significance ◽  
Enzyme Linked Immunosorbent Assay ◽  
Exact Test ◽  
Tuberculosis Patients ◽  
Patients With Diabetes

BACKGROUND: Infectious diseases and metabolic disorders would result in oxidative stress in cells. Superoxide dismutase (SOD) is an antioxidant present inside cells that acts against oxidative stress. SOD gene polymorphism can affect the activity and levels of SOD. AIM: This study aimed to analyse SOD levels and polymorphism of gene (ala16val) that regulated SOD in tuberculosis patients with diabetes mellitus in Medan city. METHODS: A total of 40 tuberculosis patients with diabetes mellitus and 40 healthy subjects participated in the study. The levels of SOD were measured using enzyme-linked immunosorbent assay (ELISA). Analysis of SOD gene polymorphism (ala16val) was done using polymerase chain reaction-restriction fragment lengths polymorphisms (PCR-RFLP) with BsaW1 as the restriction enzyme. The statistical significance was determined using the Mann Whitney test, Fisher's exact test, and Kruskal Wallis test (p < 0.05). RESULTS: The SOD levels of tuberculosis patients with diabetes mellitus were lower than those of the healthy subjects (102.474 ± 36.07 U/L vs 294.543 ± 58.75 U/L, p < 0.05). Patients of tuberculosis with diabetes mellitus tend to have more value/Val genotypes than the healthy group (57.5% vs 50%, p > 0.05). There was no association between SOD levels and SOD gene polymorphism (ala16val) in tuberculosis patients with diabetes mellitus. CONCLUSION: In this study, there was an association between the levels of SOD and tuberculosis patients with diabetes mellitus, but not for the SOD gene polymorphism (ala16val). The SOD gene polymorphism (ala16val) was not the key role to influence the SOD levels in tuberculosis patients with diabetes mellitus in Medan city.

scholarly journals Analysis of Foveal Microvascular Abnormalities in Diabetic Retinopathy Using Optical Coherence Tomography Angiography with Projection Artifact Removal

2018 ◽  
Vol 2018 ◽  
pp. 1-9 ◽  
Author(s):  
Lun Liu ◽  
Jian Gao ◽  
Weili Bao ◽  
Chengyang Hu ◽  
Yajing Xu ◽  
...  
Keyword(s):  
Optical Coherence Tomography ◽  
Diabetic Retinopathy ◽  
Optical Coherence Tomography Angiography ◽  
Vessel Density ◽  
Foveal Avascular Zone ◽  
Optical Coherence ◽  
Artifact Removal ◽  
Significant Difference ◽  
Patients With Diabetes ◽  
Capillary Plexus

Purpose. To analyze foveal microvascular abnormalities in different stages of diabetic retinopathy (DR) using optical coherence tomography angiography (OCTA) with projection artifact removal (PAR). Methods. We analyzed 93 eyes of 59 patients with diabetes—31 with no DR (no DR), 34 with mild to moderate nonproliferative DR (mild DR), and 28 with severe nonproliferative DR to proliferative DR (severe DR)—and 31 age-matched healthy controls. Sections measuring 3 × 3 mm2 centered on the fovea were obtained using OCTA. The area, perimeter, and acircularity index (AI) of the foveal avascular zone (FAZ), vessel density within a 300 μm wide region of the FAZ (FD-300), and parafoveal vessel density in the superficial capillary plexus (SCP) and deep capillary plexus (DCP) were calculated using novel built-in software with PAR. Results. There was no statistically significant difference in the FAZ area (p=0.162). There was a statistically significant difference in the FAZ perimeter (p=0.010) and the AI (p<0.001) between the four groups. There was a correlation between the AI and the increasing severity of DR (p=0.010). Statistically significant decreases of vessel density in the FD-300, SCP, and DCP were observed (all p<0.001). There was a difference in parafoveal vessel density in the DCP between the healthy control eyes and the eyes with diabetes without DR (p=0.027). There was a significant correlation between vessel density and increasing severity of DR (p<0.001). Conclusion. Compared with the FAZ area, AI allows a more helpful quantitative assessment of the changes in the FAZ. Vessel density determined using OCTA with PAR might be a useful parameter indicating the progression of DR. Parafoveal vessel density in the DCP after PAR might be a potential early biomarker of DR before appearance of clinically evident retinopathy and needs further investigation.

Desmopressin Stimulates Parallel Norepinephrine and Tissue Plasminogen Activator Release in Normal Subjects and Patients with Diabetes Mellitus

1988 ◽  
Vol 59 (02) ◽  
pp. 269-272 ◽  
Author(s):  
M B Grant ◽  
C Guay ◽  
R Lottenberg
Keyword(s):  
Diabetes Mellitus ◽  
Plasminogen Activator ◽  
Tissue Plasminogen Activator ◽  
Time Course ◽  
Vascular Endothelial Cells ◽  
Normal Subjects ◽  
Plasma Norepinephrine ◽  
Endogenous Catecholamine ◽  
Tissue Plasminogen ◽  
Patients With Diabetes

SummaryDesmopressin acetate administration markedly stimulates release of tissue plasminogen activator (t-PA) from vascular endothelial cells. The mechanism for this effect is unknown. Because infusion of epinephrine has been shown to increase t-PA levels, we examined the role of endogenous catecholamine mediation of t-PA release by desmopressin. Intravenous desmopressin acetate (0.3 μg/kg) was infused over 30 min in 9 controls and 11 subjects with diabetes mellitus, a condition associated with abnormalities of the fibrinolytic system. Plasma was collected in the supine, overnight fasted state at 15 min intervals (0-60 min) for measurement of t-PA activity, t-PA antigen and fractionated catecholamines. t-PA activity peaked at 30-45 min and subsequently decreased. The norepinephrine levels paralleled the t-PA activity. t-PA activity increased 10-fold from 0.14 ± .12 to 1.49 ± 0.79 IU/ml (Mean ± SD) and plasma norepinephrine increased 2- fold from 426 ± 90 to 780 ± 292 pg/ml. However, epinephrine and dopamine levels did not change significantly. The response to desmopressin of control and diabetic subjects was not shown to differ and their data were combined. We conclude that desmopressin increases plasma norepinephrine in addition to t-PA and that the parallel time course of change suggests a possible role for norepinephrine in mediating endothelial cell t-PA release.

Responses of Platelets to Strains of Streptococcus sanguis: Findings in Healthy Subjects, Bernard-Soulier, Glanzmann’s, and Collagen-Unresponsive Patients

1987 ◽  
Vol 57 (02) ◽  
pp. 222-225 ◽  
Author(s):  
A H Soberay ◽  
M C Herzberg ◽  
J D Rudney ◽  
H K Nieuwenhuis ◽  
J J Sixma ◽  
...  
Keyword(s):  
Platelet Aggregation ◽  
Healthy Subjects ◽  
Normal Subjects ◽  
Membrane Glycoprotein ◽  
Response Mechanism ◽  
Platelet Response ◽  
Induce Platelet Aggregation ◽  
Streptococcus Sanguis ◽  
Lag Times ◽  
Bernard Soulier Syndrome

SummaryThe ability of endocarditis and dental strains of Streptococcus sanguis to induce platelet aggregation in plasma (PRP) from normal subjects were examined and compared to responses of PRP with known platelet membrane glycoprotein (GP) and response defects. S. sanguis strains differed in their ability to induce normal PRPs to aggregate. Strains that induced PRP aggregation in more than 60% of donors were significantly faster agonists (mean lag times to onset of aggregation less than 6 min) than those strains inducing response in PRPs of fewer than 60% of donors.Platelets from patients with Bernard-Soulier syndrome aggregated in response to strains of S. sanguis. In contrast, platelets from patients with Glanzmann’s thrombasthenia and from a patient with a specific defect in response to collagen were unresponsive to S. sanguis. These observations show that GPIb and V are not essential, but GPIIb-IIIa and GPIa are important in the platelet response mechanism to S. sanguis. Indeed, the data suggests that the platelet interaction mechanisms of S. sanguis and collagen may be similar.

Effect of human galanin on the response of circulating catecholamines to hypoglycemia in man

1995 ◽  
Vol 133 (6) ◽  
pp. 723-728 ◽  
Author(s):  
Ettore C degli Uberti ◽  
Maria R Ambrosio ◽  
Marta Bondanelli ◽  
Giorgio Transforini ◽  
Alberto Valentini ◽  
...  
Keyword(s):  
Heart Rate ◽  
Healthy Subjects ◽  
Sympathetic Nerve Activity ◽  
Heart Rate Response ◽  
Statistical Significance ◽  
Inhibitory Effect ◽  
Amino Acid Residues ◽  
Nerve Activity ◽  
Receptor Stimulation

degli Uberti EC, Ambrosio MR, Bondanelli M, Trasforini G, Valentini A, Rossi R, Margutti A, Campo M. Effect of human galanin on the response of circulating catecholamines to hypoglycemia in man. Eur J Endocrinol 1995;133:723–8. ISSN 0804–4643 Human galanin (hGAL) is a neuropeptide with 30 amino acid residues that has been found in the peripheral and central nervous system, where it often co-exists with catecholamines. In order to clarify the possible role of hGAL in the regulation of sympathoadrenomedullary function, the effect of a 60 min infusion of hGAL (80 pmol·kg−1 · min−1) on plasma epinephrine and norepinephrine responses to insulin-induced hypoglycemia in nine healthy subjects was investigated. Human GAL administration significantly reduced both the release of basal norepinephrine and the response to insulin-induced hypoglycemia, whereas it attenuated the epinephrine response by 26%, with the hGAL-induced decrease in epinephrine release failing to achieve statistical significance. Human GAL significantly increased the heart rate in resting conditions and clearly exaggerated the heart rate response to insulin-induced hypoglycemia, whereas it had no effect on the blood pressure. We conclude that GAL receptor stimulation exerts an inhibitory effect on basal and insulin-induced hypoglycemia-stimulated release of norepinephrine. These findings provide further evidence that GAL may modulate sympathetic nerve activity in man but that it does not play an important role in the regulation of adrenal medullary function. Ettore C degli Uberti, Chair of Endocrinology, University of Ferrara, Via Savonarola 9, I-44100 Ferrara, Italy

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