A Nonrandomized, Open-Label, Multicenter, Phase 4 Pilot Study on the Effect and Safety of ILUVIEN® in Chronic Diabetic Macular Edema Patients Considered Insufficiently Responsive to Available Therapies (RESPOND)

PURPOSE: The aim of this study was to assess the effectiveness and safety of ILUVIEN® in patients with chronic diabetic macular edema (DME) who were insufficiently responsive to prior therapies. METHODS: This is a prospective, nonrandomized, multicenter, open-label, phase 4 pilot study assessing the effectiveness and safety of ILUVIEN® involving 12 patients insufficiently responsive to available therapies. Assessments were performed at screening, baseline, week 1, and months 1, 3, 6, 9, and 12. Demographics, medical/ophthalmic history, prior laser, anti-VEGF, and steroid treatments, and lab tests were recorded at screening. A complete ophthalmic examination and SD-OCT were performed at screening and at all follow-up visits. RESULTS: The patients showed improvements in best-corrected visual acuity (+3.7 letters), with greater improvement among pseudophakic patients (+6.8 letters) compared with phakic patients (-2.5 letters) 12 months after ILUVIEN®. The mean central subfield thickness decrease from baseline to month 12 was statistically significant, with a rapid reduction in the first week. Regarding safety, only 2 patients showed an intraocular pressure (IOP) increase over 25 mm Hg during the study, and the rise in IOP was well managed with eye drops only. CONCLUSIONS: This prospective and pilot study suggests that ILUVIEN® is safe and may be considered effective for chronic DME patients insufficiently responsive to other available therapies as it showed a rapid and sustained improvement of macular edema obtained after treatment with ILUVIEN®.info:eu-repo/semantics/publishedVersio

Effect of cyclosporin-A on the blood--retinal barrier permeability in streptozotocin-induced diabetes.

BACKGROUND: Our previous results showed that in retinas from streptozotocin (STZ)-induced diabetic rats there is an increased level of interleukin-1beta (IL-1beta). This cytokine may be involved in the expression of the inducible isoform of the nitric oxide synthase (iNOS), with consequent synthesis of large amounts of NO and blood-retinal barrier (BRB) breakdown. AIMS: The aim of this work was to examine whether the administration of cyclosporin-A (Cs-A) to STZ-induced diabetic rats inhibits the synthesis of IL-1beta and the expression of the inducible proteins, iNOS and cyclo-oxygenase-2 (COX-2) in retinal cells, and whether the activity of these proteins contribute to BRB breakdown. METHODS: The level of IL-1beta was evaluated by ELISA and the NO production by L-[3H]-citrulline formation. Expression of iNOS and COX-2 proteins was determined by two methods, western blot and immunohistochemistry. The permeability of the BRB was assessed by quantification of the vitreous protein. RESULTS AND DISCUSSION: Our results indicated that the levels of IL-1beta and NO in retinas from Cs-A-treated diabetic rats are significantly reduced, as compared to that in non-treated diabetic rats. The treatment of diabetic rats with Cs-A also significantly inhibited the expression of the inducible proteins, iNOS and COX-2. The evaluation of the vitreous protein content revealed that Cs-A also reduces the BRB permeability. Taken together, these results suggest that the increased production of the inflammatory mediators, IL-1beta and NO, in diabetes may affect the BRB permeability and therefore contribute to the development of diabetic retinopathy

Clinical manifestations of pandemic (H1N1) 2009 in the ambulatory setting

INTRODUCTION: In June 2009, the World Health Organization declared an influenza pandemic associated with the pandemic (H1N1) 2009 strain. It was summer in the northern hemisphere, and therefore travelling and vacation time, which also provided an increased opportunity for the dissemination of respiratory diseases. METHODOLOGY: We reviewed the paper case report forms from all the patients with influenza-like illnesses with nasopharyngeal samples submitted for laboratory diagnosis of pandemic (H1N1) 2009 infection during the first wave of pandemic influenza that occurred between June and August 2009, in the central region of Portugal. RESULTS: From all the patients with influenza-like illnesses, one third was found positive for pandemic (H1N1) 2009. Individuals under the age of 29 (75%) were the most affected. Most of the patients (91%) presented with fever. A group of symptoms were positively correlated with the probability of pandemic (H1N1) 2009 infection: cough, epistaxis, lack of dyspnea or vomiting, fever, headache and myalgia. CONCLUSIONS: During the first wave of the pandemic influenza, young individuals were the most affected, and in the ambulatory setting, presentation was of a mild febrile illness without complications

Tribological characterisation of magnetron sputtered Ti(C, O, N) thin films

Ti(C, O, N) thin films were prepared by magnetron sputtering and analysed in terms of their tribological properties. Surface and tribological parameters were analysed and discussed as a function of the films composition and structural features, as well as their thickness. The evolution of friction coefficient values was in concordance with the wear behaviour of the films. According to the atomic composition of the films, an increasing of the carbon percentage and a compound chemical formula closed to the stoichiometric TiC lead to a very good wear behaviour. This aspect is also directly correlated with the friction behaviour.Fundação para a Ciência e Tecnologia (FCT) SFRH/BPD/27114/2006 e PTDC/CTM/69362/200

Dynamic mechanical properties of hydroxyapatite-reinforced and porous starch-based degradable biomaterials

It has been shown that blends of starch with a poly(ethylene-vinyl-alcohol) copolymer, EVOH, designated as SEVA-C, present an interesting combination of mechanical, degradation and biocompatible properties, specially when filled with hydroxyapatite (HA). Consequently, they may find a range of applications in the biomaterials field. This work evaluated the influence of HA fillers and of blowing agents (used to produce porous architectures) over the viscoelastic properties of SEVA-C polymers, as seen by dynamic mechanical analysis (DMA), in order to speculate on their performances when withstanding cyclic loading in the body. The composite materials presented a promising performance under dynamic mechanical solicitation conditions. Two relaxations were found being attributed to the starch and EVOH phases. The EVOH relaxation process may be very useful in vivo improving the implants performance under cyclic loading. DMA results also showed that it is possible to produce SEVA-C compact surface/porous core architectures with a mechanical performance similar to that of SEVA-C dense materials. This may allow for the use of these materials as bone replacements or scaffolds that must withstand loads when implanted

Ti–Si–C thin films produced by magnetron sputtering : correlation between physical properties, mechanical properties and tribological behavior

Ti–Si–C thin films were deposited onto silicon, stainless steel and high-speed steel substrates by magnetron sputtering, using different chamber configurations. The composition of the produced films was obtained by Electron Probe Micro-Analysis (EPMA) and the structure by X-ray diffraction (XRD). The hardness and residual stresses were obtained by depth-sensing indentation and substrate deflection measurements (using Stoney’s equation), respectively. The tribological behavior of the produced films was studied by pin-on-disc. The increase of the concentration of non-metallic elements (carbon and silicon) caused significant changes in their properties. Structural analysis revealed the possibility of the coexistence of different phases in the prepared films, namely Ti metallic phase ( alpha-Ti or beta-Ti) in the films with higher Ti content. The coatings with highest carbon contents, exhibited mainly a sub-stoichiometric fcc NaCl TiC-type structure. These structural changes were also confirmed by resistivity measurements, whose values ranged from 10E3 Ohm/sq for low non-metal concentration, up to 10E6 Ohm /sq for the highest metalloid concentration. Astrong increase of hardness and residual stresses was observed with the increase of the non-metal concentration in the films. The hardness (H) values ranged between 11 and 27 GPa, with a clear dependence on both crystalline structure and composition features. Following the mechanical behavior, the tribological results showed similar trends, with both friction coefficients and wear revealing also a straight correlation with the composition and crystalline structure of the coatings

Development of new decorative coatings based on gold nanoparticles dispersed in an amorphous TiO2 dielectric matrix

The present work is devoted to the optical properties of Au:TiO2 thin films in order to clarify the role of the Au clusters inclusions in the TiO2 dielectric matrix. Three series of films containing about 30 at.% (29.2), 20 at. % (19.8) and 10 at.% (9.3) Au were deposited by dc reactive magnetron sputtering. On thermal annealing in the range from 300 to 800 °C in protective atmosphere, significant changes on the crystalline phases and clusters dimensions were detected. The most promising optical behavior was found for the film 20% Au:TiO2, where the films revealed some colour changes, evolving from several shades of grey to different tones of red. This change in the optical behaviour of the films was found to be correlated with a cluster size increase from 2 to 17 nm. For higher size values (>20 nm) the films, independently of the Au content, showed a golden appearance colour. The optical changes were confirmed by reflectivity and CIELab colour measurements. Regarding the films with 10 and 30 at.% Au, the results confirmed that there is an evident range of compositions and clusters size where the SPR is more evident. Sample A (10 at.% Au) it seems to be in the lower limit of the SPR showing a typical interferometric behavior on the reflectivity measurements, similar to the TiO2 optical behavior. Regarding the 30 at.% Au one, the results seems to indicate that the amount of gold particles and their grain size is in the upper limit to show a SPR activity.Fundação para a Ciência e Tecnologia (FCT) - PTDC/CTM/70037/200

Lymphocyte Subpopulations in Sjögren’s Syndrome Are Distinct in Anti-SSA-Positive Patients and Related to Disease Activity

Objectives: Sjögren's syndrome (SjS) patients exhibit great phenotypical heterogeneity, reinforced by the positiveness of anti-SSA antibody. We aimed to evaluate lymphocyte subpopulations in SSA-positive (SSA+SjS) and SSA-negative (SSA-SjS) SjS patients, Sicca patients, and healthy controls (HC), and to investigate associations between lymphocyte subpopulations and disease activity in SjS. Methods: According to the fulfilment of the ACR/EULAR 2016 classification criteria, patients were included as SjS or as Sicca. HC were selected from the Ophthalmology outpatient clinic. Lymphocyte subpopulations were characterized by flow cytometry. Statistical analysis was performed with GraphPad PrismTM, with statistical significance concluded if p < 0.05. Results: We included 53 SjS patients (38 SSA+ and 15 SSA-), 72 Sicca, and 24 HC. SSA+SjS patients presented increased IL-21+CD4+ and CD8+ T cells compared to Sicca and HC, whereas compared to SSA-SjS patients, only IL-21+CD4+ T cell percentages were increased and Tfh17 percentages and numbers were decreased. Compared to Sicca and HC, SSA+SjS patients had higher levels of CD24HiCD38Hi B cells, naïve B cells, and IgM-/+CD38++ plasmablasts, and lower levels of memory B cells, including CD24HiCD27+ B cells. SSA+SjS patients with clinically active disease had positive correlations between ESSDAI and IL-21+CD4+ (p = 0.038, r = 0.456) and IL-21+CD8+ T cells (p = 0.046, r = 0.451). Conclusions: In SjS, a distinct lymphocyte subset distribution profile seems to be associated with positive anti-SSA. Moreover, the association between ESSDAI and IL-21+CD4+ and IL-21+CD8+ (follicular) T cells in SSA+SjS patients suggests the involvement of these cells in disease pathogenesis and activity, and possibly their utility for the prognosis and assessment of response to therapy. Key Points • SSA+SjS patients have a pronounced naïve/memory B cell imbalance. • SSA+SjS patients have more active disease associated with IL-21+CD4+ and IL-21+CD8+ follicular T cell expansion. • IL-21+CD4+ and IL-21+CD8+ T cell quantification may be useful for the prognosis and assessment of response to therapy.info:eu-repo/semantics/publishedVersio

Structural evolution in ZrNxOy thin films as a function of temperature

Single-layered zirconium oxynitride (ZrNxOy) thin films have been deposited on steel substrates, at a constant temperature of 300 °C, by radiofrequency (rf) reactive magnetron sputtering of a pure Zr target in an argon-oxygen-nitrogen atmosphere. The variation of the flow rate of the reactive gases enabled changes in the composition and structure of the films. X-ray diffraction (XRD) and glancing incidence X-ray diffraction (GIXRD) were used to study the as-deposited films and their structural changes during or after heat treatment, from 400 to 900 °C, in controlled atmosphere and in vacuum.http://www.sciencedirect.com/science/article/B6TVV-4DPYN97-6/1/3785b40b130ad12af7221c230d2968c