Transforming growth factor β1 (TGFβ1) is a proinflammatory cytokine that has been implicated in the pathogenesis of diabetic retinopathy (DR), particularly in the late phase of disease. The aim of ...the present study was to validate serum TGFβ1 as a diagnostic and prognostic biomarker of DR stages. Thirty-eight subjects were enrolled and, after diagnosis and evaluation of inclusion and exclusion criteria, were assigned to six groups: (1) healthy age-matched control, (2) diabetic without DR, (3) non-proliferative diabetic retinopathy (NPDR) naïve to treatment, (4) NPDR treated with intravitreal (IVT) aflibercept, (5) proliferative diabetic retinopathy (PDR) naïve to treatment and (6) PDR treated with IVT aflibercept. Serum levels of vascular endothelial growth factor A (VEGF-A), placental growth factor (PlGF) and TGFβ1 were measured by means of enzyme-linked immunosorbent assay (ELISA). Foveal macular thickness (FMT) in enrolled subjects was evaluated by means of structural-optical coherence tomography (S-OCT). VEGF-A serum levels decreased in NPDR and PDR patients treated with aflibercept, compared to naïve DR patients. PlGF serum levels were modulated only in aflibercept-treated NPDR patients. Particularly, TGFβ1 serum levels were predictive of disease progression from NPDR to PDR. A Multivariate ANOVA analysis (M-ANOVA) was also carried out to assess the effects of fixed factors on glycated hemoglobin (HbA1c) levels, TGFβ1, and diabetes duration. In conclusion, our data have strengthened the hypothesis that TGFβ1 would be a biomarker and pharmacological target of diabetic retinopathy.
Macular peeling combined or followed by intravitreal dexamethasone implant (DEX-i) was recommended as an efficacy approach for tractional diabetic macular edema (tDME). Knowing the synergistic effect ...of cataract surgery and DEX-i one month earlier in eyes with DME, we compared Epiretinal Membrane/Inner Limiting Membrane (ERM/ILM) peeling preceded by DEX-i one month before versus ERM/ILM peeling alone for the treatment of tDME. A retrospective study on patients affected by tDME who underwent ERM/ILM peeling one month after DEX-i (n = 11; Group A) or ERM/ILM peeling alone (n = 10; Group B) was performed. Longitudinal comparison of best-correct visual acuity (BCVA), central retinal thickness (CRT), and intraocular pressure (IOP) between the time of surgery (T
) and each time point (months 1,3,5,6) within and among the groups were assessed. To evaluate the repeated measurements of BCVA, CRT, and IOP, a linear mixed-effects model was used. In Group A, DEX-i significantly improved mean BCVA and CRT (P < 0.001) just after 1 month (T
). After ERM/ILM peeling, mean BCVA and CRT significantly improved from month 1 in Group A and month 3 in Group B. Mixed model revealed a significant difference in BCVA (P ≤ 0.0001) and CRT (P ≤ 0.02) at different time-points among the groups with better results in Group A. Neither complications nor uncontrolled IOP increase was detected. ERM/ILM peeling confirmed its effectiveness in treating tDME. DEX-i performed one month before surgery seemed to be a safe approach and ensured a greater and faster recovery considering functional and tomographic parameters.
The aviation sector is facing a massive change in terms of replacing the currently used fossil jet fuels (Jet A, JP5, etc.) with non-fossil jet fuels from sustainable feedstocks. This involves ...several challenges and, among them, we have the fundamental issue of current jet engines being developed for the existing fossil jet fuels. To facilitate such a transformation, we need to investigate the sensitivity of jet engines to other fuels, having a wider range of thermophysical specifications. The combustion process is particularly important and difficult to characterize with respect to fuel characteristics. In this study, we examine premixed and pre-vaporized combustion of dodecane, Jet A, and a synthetic test fuel, C1, based on the alcohol-to-jet (ATJ) certified pathway behind an equilateral bluff-body flameholder, spray combustion of Jet A and C1 in a laboratory combustor, and spray combustion of Jet A and C1 in a single-sector model of a helicopter engine by means of numerical simulations. A finite rate chemistry (FRC) large eddy simulation (LES) approach is adopted and used together with small comprehensive reaction mechanisms of around 300 reversible reactions. Comparison with experimental data is performed for the bluff-body flameholder and laboratory combustor configurations. Good agreement is generally observed, and small to marginal differences in combustion behavior are observed between the different fuels.
Background.—The vasoactive peptide, calcitonin gene‐related peptide (CGRP), is released from primary afferent neurons in the trigemino‐vascular circulation during migraine headache. CGRP at ...physiological concentrations and possibly via stimulation of its selective receptors on T‐cells, triggers the secretion of cytokines. Cytokines play an important role in several physiological and pathological settings such as immunology, inflammation, and pain.
Objective.—To investigate plasma levels of pro‐ and anti‐inflammatory cytokines in migraineurs and healthy controls.
Methods.—We studied 25 migraine patients, during and outside attacks, and 18 healthy control subjects measuring plasma levels of IL‐6, IL‐10, tumor necrosis factor alpha (TNFα), IL‐4, IL‐1β, and IL‐2 using ELISA.
Results.—Circulating levels of IL‐10, TNFα, and IL‐1β during attacks were significantly higher in comparison to their levels outside attacks (P= .0003, P= .03, and P= .05, respectively). IL‐10 and TNF serum levels were higher in patients studied soon after headache onset and lower over time (P= .004 and P= .05).
Conclusion.—Our results suggest that TNFα, IL‐1β, and IL‐10 may be involved in the pathogenesis of migraine attacks.
Background: An intravitreal dexamethasone implant (DEX-I) was found to be effective and safe for the treatment of cystoid macular edema (CME) after vitrectomy for rhegmatogenous retinal detachment ...(RRD) and in silicone oil (SO)-filled eyes. We aimed to investigate the efficacy and safety of DEX-I at the time of SO removal for the treatment of recalcitrant CME after successful RRD repair. Methods: A retrospective review of the medical records was performed on 24 consecutive patients (24 eyes) with recalcitrant CME after RRD repair who were treated with a single 0.7-mg DEX-I at the time of SO removal. The main outcome measures were changes in best-corrected visual acuity (BCVA) and central macular thickness (CMT). A regression model was performed to assess the relationship between BCVA and CMT at 6 months and independent variables. Results: In all 24 patients, CME occurred after RRD repair and remained despite topical therapy. The mean time of CME onset was 27.4 ± 7.7 days after vitrectomy. The mean time between vitrectomy and DEX-I was 106.8 ± 10.1 days. The mean CMT was significantly decreased from 429.6 ± 59.1 µm at baseline to 294 ± 46.4 µm at month 6 (p < 0.0001). The mean BCVA significantly improved from 0.99 ± 0.3 at baseline to 0.60 ± 0.3 at month 6 (p < 0.0001). An elevation of intraocular pressure was observed in one (4.1%) eye, which was medically managed. A univariate regression model revealed a relationship between month-6 BCVA after DEX-I and gender (β = −0.27; p = 0.03) and macular status (β = −0.45; p = 0.001) when RRD occurred. No relationship between month-6 CMT and independent variables was found. Conclusions: DEX-I at the time of SO removal had an acceptable safety profile and achieved favorable outcomes in eyes affected by recalcitrant CME that occurred after RRD repair. RRD-related macular status is significantly associated with visual acuity after DEX-I.
Introduction
The aims of this work were to evaluate the real-world efficacy and safety of a loading dose of intravitreal faricimab in eyes with active neovascular age-related macular degeneration ...(n-AMD) or diabetic macular edema (DME) and to analyze the treatment outcome in relation to specific biomarkers.
Methods
Patients with active n-AMD or DME, treated with four monthly intravitreal injections of faricimab, were enrolled in this retrospective, uncontrolled study. Best-corrected visual acuity (BCVA), central subfield thickness (CST), presence of retinal fluid (RF) on optical coherence tomography (OCT), and adverse events were assessed at baseline and at weeks 4, 8, 12, and 16. Predefined biomarkers were evaluated at baseline (BL) and at last visit.
Results
Sixteen eyes of 15 patients with n-AMD (n-AMD group) and 15 eyes of 12 patients with DME (DME group) were included. Mean (± standard deviation) logarithm of minimum angle of resolution (logMAR) BL BCVA changed from 0.68 (± 0.43) to 0.53 (± 0.36;
P
= 0.13) and from 0.51 (± 0.34) to 0.32 (± 0.24;
P
: 0.048) at week 16 in n-AMD and DME group, respectively. A statistically significant mean CST reduction was reported in both groups at last visit (n-AMD: − 166.5 μm;
P
= 0.0009/DME: − 110.8 μm;
P
= 0.0086). Seventy-five and 33% of eyes with n-AMD and DME respectively achieved complete RF resolution at last visit. Subfoveal inner and outer retinal damage correlated with a lower final BCVA in n-AMD group. The presence of large (> 100 μm) juxtafoveal microaneurysms (MAs) was significantly correlated with a higher chance of residual fluid in eyes with DME.
Conclusions
Both n-AMD and DME groups achieved satisfactory anatomical results after a loading-dose of intravitreal faricimab. BCVA improvement might be hampered by pre-existing retinal damage in eyes with n-AMD. Large, juxtafoveal MAs might represent a hallmark of a slower anatomical response to the treatment in eyes with DME.
To assess functional and anatomical outcomes of intravitreal anti-Vascular Endothelial Growth Factor (anti-VEGF) monotherapy
combined with verteporfin Photodynamic Therapy (PDT) for Retinal ...Angiomatous Proliferation (RAP).
Studies reporting outcomes of intravitreal anti-VEGF monotherapy and/or in combination with verteporfin PDT in RAP eyes with a follow-up ≥ 12 months were searched. The primary outcome was the mean change in best corrected visual acuity (BCVA) at 12 months. Mean change in central macular thickness (CMT) and mean number of injections were considered as secondary outcomes. The mean difference (MD) between pre- and post-treatment values was calculated along with 95% Confidence Interval (95% CI). Meta-regressions were performed to assess the influence of anti-VEGF number of injections on BCVA and CMT outcomes.
Thirty-four studies were included. A mean gain of 5.16 letters (95% CI = 3.30-7.01) and 10.38 letters (95% CI = 8.02-12.75) was shown in the anti-VEGF group and combined group, respectively (anti-VEGF group vs. combined group,
< 0.01). A mean CMT reduction of 132.45 µm (95% CI = from -154.99 to -109.90) and 213.93 µm (95% CI = from -280.04 to -147.83) was shown in the anti-VEGF group and combined group, respectively (anti-VEGF group vs. combined group,
< 0.02). A mean of 4.9 injections (95% CI = 4.2-5.6) and 2.8 injections (95% CI = 1.3-4.4) were administered over a 12-month period in the anti-VEGF group and combined group, respectively. Meta-regression analyses showed no influence of injection number on visual and CMT outcomes. High heterogeneity was found across studies for both functional and anatomical outcomes.
A combined approach with anti-VEGF and PDT could provide better functional and anatomical outcomes in RAP eyes compared with anti-VEGF monotherapy.
To evaluate the efficacy of vitrectomy combined with intravitreal dexamethasone implant vs. vitrectomy without the implant in patients with epiretinal membrane (ERM) by conducting a systematic review ...and meta-analysis.
Studies that compared ERM vitrectomy with and without intraoperative dexamethasone implant with a follow-up ≥3 months were included. The primary outcome was mean best corrected visual acuity (BCVA) change between eyes undergoing ERM vitrectomy combined with dexamethasone implant (DEX group) and eyes undergoing ERM vitrectomy alone (control group) at 3 months. Secondary outcomes included mean BCVA change at 6 months and mean optical coherence tomography central macular thickness (CMT) change at both 3-months and 6-months follow-up. Mean differences (MDs) with their 95% confidence interval (95%CI) were calculated. Meta-analyses were based either on random effect model or fixed effect model according to heterogeneity.
Four studies were included. At 3 months, ERM vitrectomy combined with dexamethasone implant yielded a greater visual gain compared to vitrectomy alone (MD = 9.7; 95%CI = 2.6-16.8;
= 0.01). However, significant heterogeneity was found. A sensitivity analysis excluding the only retrospective non-randomized study confirmed a greater visual gain in the DEX group (MD = 7.1; 95%CI = 2.7-11.6;
< 0.01), with no heterogeneity. At 6 months, a non-significant but borderline difference in visual gain was shown between in the two groups (MD = 5.1; 95%CI = -0.3-10.5;
= 0.06), with no heterogeneity. Three-month analysis of CMT revealed a greater reduction in the DEX group (MD = -80.2; 95%CI =-149.1-11.2;
= 0.02), but with significant heterogeneity. A sensitivity analysis excluding the only retrospective non-randomized study allowed to reduce heterogeneity, but no difference in 3-months CMT change was found between the two groups (MD = -50.0; 95%CI = -106.2-6.2;
= 0.08). At 6 months, no difference in CMT change was shown between the two groups (MD = -48.5; 95%CI = -120.5-23.5;
= 0.19), with significant heterogeneity.
Intraoperative dexamethasone implant in eyes undergoing vitrectomy for ERM provided a better visual outcome at 3 months compared to ERM vitrectomy without the implant, with limited evidence of better anatomic outcome as well. Further studies are needed to ascertain whether dexamethasone implant would ensure a significant long-term visual benefit as a result of a faster reduction of macular thickening.
Since this advent, additive manufacturing (AM) has grown steadily and found applications across all types of sectors. While the great development of such technologies has improved the quality of ...prints and expanded the availability of materials, AM still has some limitations regarding its physical scaling. This paper will briefly present the state-of-the-art of large-scale additive manufacturing and subsequently greater attention will be given to extrusion-based 3D printing. Specifically, we will discuss about large format additive manufacturing (LFAM) or big area additive manufacturing (BAAM), a technology based on material extrusion born a few years ago. These systems are characterized by higher deposition rate and lower costs of the material compared to fused filament fabrication (FFF) printers; moreover, they allow to obtain parts with better properties (e.g., adding carbon or glass fibers). The world of research has shown great interest in large-scale material extrusion technologies, which appear to be quite competitive with conventional manufacturing processes and which will find increasing application in the industrial field. With the aim of developing a tool for orienting researchers and technicians in this complex field, the present paper presents a systematic review of the actual market of machines, the research in extrudable materials and related applications concerning large-scale 3D printing, and in particular the LFAM.
A bottom-up electricity characterisation methodology of the building stock at the local level is presented. It is based on the statistical learning analysis of aggregated energy consumption data, ...weather data, cadastre, and socioeconomic information. To demonstrate the validity of this methodology, the characterisation of the electricity consumption of the whole province of Lleida, located in northeast Spain, is implemented and tested. The geographical aggregation level considered is the postal code since it is the highest data resolution available through the open data sources used in the research work. The development and the experimental tests are supported by a web application environment formed by interactive user interfaces specifically developed for this purpose. The paper’s novelty relies on the application of statistical data methods able to infer the main energy performance characteristics of a large number of urban districts without prior knowledge of their building characteristics and with the use of solely measured data coming from smart meters, cadastre databases and weather forecasting services. A data-driven technique disaggregates electricity consumption in multiple uses (space heating, cooling, holidays and baseload). In addition, multiple Key Performance Indicators (KPIs) are derived from this disaggregated energy uses to obtain the energy characterisation of the buildings within a specific area. The potential reuse of this methodology allows for a better understanding of the drivers of electricity use, with multiple applications for the public and private sector.
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