Recent developments in biologic therapies for the treatment of patients with systemic lupus erythematosus.

SLE has a complex pathogenesis, and multiple therapeutic targets have been discovered in recent years. In spite of belimumab being approved by the US Food and Drug Administration and the widespread use of rituximab, there have been many failed attempts to treat SLE successfully using biologic agents. In this review, we consider newer biologic approaches that might offer the hope of improving the outcome of SLE patients. These include the fully humanized anti-CD20 mAbs, PEGylated anti-CD40L, IFNα inhibitors, rigerimod and immune complexes blockade.

Strabismus and Health Related Quality of Life in a pediatric Portuguese population.

Introduction: Strabismus is a common condition among children, and its psychosocial impact has been demonstrated in recent years. The interest in a more comprehensive approach was enhanced by the recognition of health as a four-dimensional concept, arising the term Health-related Quality of Life. Therefore, we aim to evaluate the influence of strabismus in Health-Related Quality of Life of a Portuguese pediatric population. Material and Methods: Case-control prospective transversal study enrolling children between 5 and 12 years old. All had a complete orthoptic and ophthalmological evaluation, followed by an interview with a legal representative to answer the Pediatric Quality-of-Life Inventory 4.0, proxy-version. Results: Seventy-one children were included, 35 in the control group (CG) and 36 in the strabismus group (SG). In the SG, 30 (83.3%) patients had esotropia, 20 (55.6%) had more than 10 prismatic diopters and 26 (72.2%) were already surgically treated. Overall, SG was not statistically different from the CG, showing only mild inferior performance (p > .05). Furthermore, children with exotropia, higher deviations, none or gross stereoacuity and treatment-naïve, scored worse, especially in emotional, social, educational and psychosocial scores although not statistically significant (p > .05). Conclusion: This is the first prospective study addressing HRQoL and strabismus in a pediatric Portuguese population. It would be relevant to further address this issue in order to delineate more effective and global treatment strategies, not only considering ophthalmological goals but also the well-being of both children and guardians.

The Effect of Upper Eyelid Blepharoplasty on Corneal Tomography and Epithelial Profile.

Introduction: Upper tarsal mechanical forces influence corneal epithelial thickness profile, which could modulate corneal astigmatism. Upper eyelid blepharoplasty reduces upper tarsal strength and may have an impact on ocular surface. The aim of this study is to evaluate the effect of upper eyelid blepharoplasty on corneal epithelial thickness profile, astigmatism and aberrations. Methods: Patients with dermatochalasis underwent bilateral upper eyelid blepharoplasty. Anterior segment optical coherence tomography (AS-OCT) (Zeiss Cirrus 5000 HD-OCT) and Pentacam (Oculus, Wetzlar Germany) were performed before surgery and in the 8th postoperative week. Corneal epithelial thickness, keratometry, aberrations and asphericity were considered for statistical purposes. Only right eyes were considered. A p-value lower than 0.05 was considered significant. Results: Thirty eyes of 30 patients were included. The degree of astigmatism did not change after surgery (0.95D vs 0.83D, p=0.23). The difference between preoperative and postoperative steepest axis was 3.1° (p=0.04) with a tendency to change toward the vertical meridian. Mean epithelial thickness was higher in the inferior region both pre- and postoperatively and did not change. ET in the superior octant was lower (42 µm vs 45 µm, p<0.01) and the difference between inferior and superior octants (I-S) was higher (7 µm vs 3 µm, p<0.001) before surgery. There were no statistically significant changes in corneal aberrations (p=0.52) and asphericity (p=0.41) after surgery. Conclusion: Our results support that upper tarsus pressure influences epithelial thickness profile and, consequently, the corneal steepest keratometry. These results lead us to postulate that upper eyelid blepharoplasty may influence biometric and keratometric measurements.

Corneal Epithelial Thickness Changes After Topical Treatment of Dry Eye Disease in Primary Sjögren Syndrome.

Purpose: To evaluate the changes on epithelial thickness before and after topical treatment in primary Sjögren syndrome-associated dry eye disease (SS-DED). Methods: This was a prospective study that included referred women with SS-DED and healthy age-matched controls. Corneal epithelial thickness was evaluated using high-definition anterior segment optical coherence tomography (Cirrus 5000 HD-OCT) in the baseline first consultation, and four weeks after treatment with preservative free 1mg/1mL sodium hyaluronate. Schirmer test 1 (ST1), tear break-up time (TBUT), tear meniscus height (TMH), SICCA Ocular Surface Score (SICCA OSS) and Ocular Surface Disease Index (OSDI) were evaluated. Statistical significance was defined as p-value <0.05. Results: The study included 40 eyes, 20 with SS-DED and 20 controls. At baseline, SS-DED patients had lower ST1 (11.1 ± 2.2mm vs 14.1 ± 3.1mm, p<0.01), faster TBUT (9.1 ± 1.8s vs 13.2 ± 1.1s, p<0.01) and lower TMH (211.2 ± 68.4 µm vs 217.2 ± 60.1µm; p<0.01) than the control group, whereas SICCA OSS and OSDI were higher (p<0.01). The superior epithelium was thinner in SS-DED group (41.1 ± 3.2 µm vs 43.1± 2.3 µm, p<0.01). After treatment, ST1, TBUT, TMH, SICCA OSS, and OSDI improved (p<0.01), and superior epithelium thickened (p<0.01) in the SS-DED group. Conclusion: Treatment with sodium hyaluronate improved ST1, TBUT, TMH, SICCA-OSS, and OSDI score. Superior epithelium tends to be thinner in SS-DED but becomes thicker with treatment. Our results seem to illustrate the morphological changes in the corneal epithelium in DED, which could be further recognized as a clinical biomarker of SS-DED.

The Study of New NiTi Actuators to Reinforce the Wing Movement of Aircraft Systems.

Actuators using Shape Memory Alloy (SMA) springs could operate in different mechanical systems requiring geometric flexibility and high performance. The aim of the present study is to highlight the potential of these actuators, using their dimensional variations resulting from the phase transformations of NiTi springs (SMA) to make the movements of the system's mobile components reversible. This reversibility is due to thermal-induced martensitic transformation of NiTi springs. The transformation promotes the extended and retracted of the springs as the phase changing (martensite-austenite) creates movement in part of the system. Therefore, the phase transition temperatures of NiTi, evaluated by differential scanning calorimetry (DSC), are required to control the dimensional variation of the spring. The influence of the number of springs in the system, as well as how impacts on the reaction time were evaluated. The different numbers of springs (two, four, and six) and the interspaces between them made it possible to control the time and the final angle attained in the mobile part of the system. Mechanical resistance, maximum angle, and the system's reaction time using different NiTi springs highlight the role of the actuators. Fused Deposition Modelling (FDM)/Material Extrusion (MEX) or Selective Laser Sintering (SLS) was selected for shaping the composite matrix system. A new prototype was designed and developed to conduct tests that established the relationship between the recoverable deformation of the matrix suitable for the application as well as the number and distribution of the actuators.

Searching New Solutions for NiTi Sensors through Indirect Additive Manufacturing.

Shape Memory Alloys (SMAs) can play an essential role in developing novel active sensors for self-healing, including aeronautical systems. However, the NiTi SMAs available in the market are almost limited to wires, small sheets, and coatings. This restriction is mainly due to the difficulty in processing NiTi through conventional processes. Thus, the objective of this study is to evaluate the potential of one of the most promising routes for NiTi additive manufacturing-material extrusion (MEX). Optimizing the different steps during processing is mandatory to avoid brittle secondary phases formation, such as Ni3Ti. The prime NiTi powder is prealloyed, but it also contains NiTi2 and Ni as secondary phases. The present study highlights the role of Ni and NiTi2, with the later having a melting temperature (Tm = 984 °C) lower than the NiTi sintering temperature, thus allowing a welcome liquid phase sintering (LPS). Nevertheless, the reaction of the liquid phase with the Ni phase could contribute to the formation of brittle intermetallic compounds, particularly around NiTi and NiTi2 phases, affecting the final structural properties of the 3D object. The addition of TiH2 to the virgin prealloyed NiTi powder was also studied and revealed the non-formation of Ni3Ti for a specific composition. The balancing addition of extra Ni revealed priority in the Ni3Ti appearance, emphasizing the role of Ni. Feedstocks extruded (filaments) and green strands (layers), before and after debinding & sintering, were used as homothetic of 3D objects for evaluation of defects (microtomography), microstructures, and mechanical properties. The composition of prealloyed powder with 5 wt.% TiH2 addition after sintering showed a homogeneous matrix with the NiTi2 second phase uniformly dispersed.

Safety of intravitreal triamcinolone and its impact on optic nerve morphology in patients treated for diabetic macular edema.

PURPOSE: To assess the impact of one intravitreal injection (IVT) of Triamcinolone Acetonide (TA) on intraocular pressure (IOP) and optic nerve structural parameters in patients treated for Diabetic Macular Edema (DME). METHODS: This retrospective study included patients with DME that were naïve to intraocular steroids and underwent one IVT of TA of 4 mg/0.1 mL and age-matched controls with DME without criteria for IVT. Patients records were reviewed for IOP (at baseline and a month after IVT) and optic nerve parameters measured by optical coherence tomography (up to 6 months before and 6 months after IVT). Exclusion criteria included glaucoma and treatment with hypotensive agents. RESULTS: Twenty-six eyes were included in the Control Group and 29 in the IVT Group, with a mean age of 65.10 ± 10.08 and 67.30 ± 4.71 years, respectively (p = 0.06). At baseline, IOP and optic nerve measurements were equivalent between groups (p > 0.05). One month after IVT, mean IOP measurements in IVT Group were higher than those of controls (17.84 ± 4.50 vs 11.59 ± 3.09 mmHg, p < 0.001). Ocular hypertension (OHT) developed in 17.24% of cases and reversed with topical medication. After one IVT, vertical cup/disc ratio was higher (0.57 ± 0.25 vs 0.60 ± 0.14, p = 0.04) and retinal nerve fiber layer thickness was globally lower (mean: 91.03 ± 4.25 vs 81.33 ± 19.10 µm, p = 0.001) in the IVT Group. CONCLUSION: Our results confirmed that intravitreal TA results in IOP increase. This seems to negatively affect optic nerve morphology, even in patients without OHT or adequately treated with hypotensive agents.

Corneal Epithelium Asymmetry in Children With Atopy: The Effect of Hand Dominance.

Purpose: To evaluate the effect of eye rubbing on the epithelial thickness profile in tomographically normal corneas by AS-OCT and to compare right and left eyes in right-handed children. Methods: Thirty right-handed boys (mean age 11.2 years) with ocular allergy and history of eye rubbing were evaluated using Scheimpflug (Pentacam HR, Oculus Wetzlar, Germany) and anterior segment optical coherence tomography. Epithelial thickness (ET) and full corneal thickness (CT) parameters were compared between right and left eyes with a non-parametric Mann-Whitney test. A p-value lower than 0.05 was considered for statistical significance. Results: No eyes had topometric nor tomographic criteria for keratoconus. The min-max ET was lower in right eyes (-2.8 µm vs -3.5; p = 0.02). The difference between inferior and superior (I-S) octants was lower in right eyes (1.1 µm vs 1.9 µm; p = 0.03) as a result of inferotemporal thinning. The highest ET difference was registered between nasal and temporal octants and was more pronounced in the right eyes (2 µm vs 3.1 µm; p < 0.001). Conclusion: AS-OCT analyses reveal different epithelial thickness patterns between the eyes in young atopic patients, likely eye rubbers. Inferior and temporal epithelial thickness seem to be more affected by thinning in the eye on the side of the dominant hand.

Evaluating the Injection Moulding of Plastic Parts Using In Situ Time-Resolved Small-Angle X-ray Scattering Techniques.

In this study, we describe the design and fabrication of an industrial injection moulding system that can be mounted and used on the NCD-SWEET small-angle X-ray scattering beamline at ALBA. We show how highly useful time-resolved data can be obtained using this system. We are able to evaluate the fraction of the material in the mould cavity and identify the first material to solidify and how this varies with the injection temperature. The design follows current industrial practice and provides opportunities to collect time-resolved data at several points within the mould cavity so that we can build up a 4D perspective of the morphology and its temporal development. The quantitative data obtained will prove invaluable for the optimisation of the next generation of injection moulding techniques. This preliminary work used results from the injection moulding of a general-purpose isotactic polypropylene.

Preliminary Clinical Outcomes of a New Enhanced Depth of Focus Intraocular Lens.

PURPOSE: To assess the preliminary clinical outcomes and patient satisfaction of the new enhanced depth of focus (EDOF) LuxSmart™ intraocular lens IOL and to compare with a conventional monofocal IOL (Akreos™) in patients who had undergone bilateral cataract surgery. METHODS: Twelve patients underwent bilateral LuxSmart IOL implantation, and twelve underwent bilateral Akreos IOL implantation. Best-corrected distance (CDVA) and uncorrected distance visual acuity (UDVA), uncorrected intermediate visual acuity (UIVA) at 66cm, uncorrected near visual acuity (UNVA) at 40cm and defocus curve were assessed. Patients-reported visual function was inquired by Catquest-9SF. The presence of photic phenomena was evaluated. A p-value lower than 0.05 was considered for statistical significance. RESULTS: The mean IOL power was +21.90D in LuxSmart group and +22.30D in Akreos. Monocular UDVA (p = 0.32) and CDVA (p = 0.52) did not differ between groups. The average binocular UIVA (0.18 ± 0.12 logMAR vs. 0.30 ± 0.13 logMAR, p < 0.001) and UNVA (0.38 ± 0.14 logMAR vs. 0.44 ± 0.17 logMAR, p = 0.02) were higher in LuxSmart IOL group. No patients reported disabling photic phenomena in either group. CONCLUSION: This study shows that new LuxSmart EDOF IOL achieved higher performance for intermediate and near vision compared with a conventional monofocal IOL, without increasing the risk of dysphotopsias. LuxSmart may be an attractive and safe option for patients who desire spectacle independence for distance and intermediate vision after cataract surgery.

In Search of the Optimal Conditions to Process Shape Memory Alloys (NiTi) Using Fused Filament Fabrication (FFF).

This research was performed so as to investigate the additive manufacturing of NiTi shape memory alloys, which is associated with direct processes, such as selective laser melting. In addition to its expensive production costs, NiTi readily undergoes chemical and phase modifications, mainly as a result of Ni loss during processing as a result of high temperatures. This research explores the potential usefulness of NiTi as well as its limitations using indirect additive processes, such as fused filament fabrication (FFF). The first step was to evaluate the NiTi critical powder volume content (CPVC) needed to process high-quality filaments (via extrusion). A typical 3D printer can build a selected part/system/device layer-by-layer from the filaments, followed by debinding and sintering (SDS), in order to generate a near-net-shape object. The mixing, extruding (filament), printing (shaping), debinding, and sintering steps were extensively studied in order to optimize their parameters. Moreover, for the sintering step, two main targets should be met, namely: the reduction of contamination during the process in order to avoid the formation of secondary phases, and the decrease in sintering temperature, which also contributes to reducing the production costs. This study aims to demonstrate the possibility of using FFF as an additive manufacturing technology for processing NiTi.

Very delayed lupus nephritis: a report of three cases and literature review.

Lupus nephritis (LN) affects up to 50% of patients with Systemic Lupus Erythematosus (SLE) and is associated with a worse prognosis. LN usually develops within the first 5 years of the onset of the disease. We report three patients with very delayed LN (DLN) diagnosed after 15 or more years after SLE diagnosis. The three patients were non-Caucasian women with adolescent or adult-onset SLE. Each had antinuclear, anti-dsDNA and anti-Ro antibodies. Hydroxychloroquine was prescribed for each. Their disease courses were characterised by sporadic non-renal flares controlled by steroids and, in two cases, by one cycle of rituximab. Unexpectedly, they developed proteinuria, haematuria and lowering of estimated glomerular filtration rate with clinical signs of renal disease. LN was confirmed by renal biopsy. Reviewing them, each showed serological signs of increasing disease activity (rising levels of anti-dsDNA antibodies and fall in C3) that predated clinical or laboratory signs of LN by 1-3 years. Reviewing the literature, we found a lack of knowledge about DLN starting more than 15 years after SLE diagnosis. With the increasing life expectancy of patients with SLE it is likely that more cases of very DLN will emerge.

Clinical Presentation and Long-Term Outcomes of Systemic Sclerosis Portuguese Patients from a Single Centre Cohort: A EUSTAR Registration Initiative.

INTRODUCTION: Systemic sclerosis is a complex disorder that requires systematic screening. Our objective is to report the European Scleroderma Trials and Research group centre affiliation and its impact in our clinical practice. MATERIAL AND METHODS: The European Scleroderma Trials and Research group affiliation process, database update and current patient evaluation, with respect to demographic and clinical features. Cumulative mortality was analysed. RESULTS: We identified 19 female patients (which met all the American College of Rheumatology/ European League Against Rheumatism 2013 criteria for systemic sclerosis) under current follow-up, divided according to the LeRoy classification into diffuse cutaneous (n = 5), limited cutaneous (n = 11) and limited (n = 3) types, followed for a median period of 5, 12 and 6 years, respectively. Raynaud´s phenomenon and abnormal nailfold capillaries were universally present. Interstitial lung disease was absent in the limited cutaneous form but present in 100% of the diffuse subtype. Pitting scars were more common in the diffuse form. Active disease was also more frequent in the diffuse form, and most patients with active disease were treated with anti-endothelin receptor antagonists. Over 21 years (from 1994 to 2015) the mortality rate was 55% (n = 23/42). Age at time of death was significantly lower in the diffuse subtype. DISCUSSION: Our single centre cohort shares many features with larger and international reports and more specifically is in accordance with patient characteristics described in the European Scleroderma Trials and Research group registries. CONCLUSION: The European Scleroderma Trials and Research group registration motivated our systematic patient characterization and may be used as a tool for homogenous disease registries.

Introdução: A esclerose sistémica é uma doença complexa que requer uma vigilância regular e sistemática. Este estudo teve como objetivo divulgar a afiliação da nossa Unidade no registo Europeu Scleroderma Trials and Research group e o seu impacto na prática clínica. Material e Métodos: Processo de afiliação Scleroderma Trials and Research group, atualização da base de dados, avaliação sistemática das características demográficas e clínicas dos doentes em seguimento e análise da mortalidade cumulativa. Resultados: Foram identificados 19 doentes do sexo feminino (com preenchimento completo dos critérios de classificação de esclerose sistémica do American College of Rheumatology/ European League Against Rheumatism 2013), seguidas no momento atual e divididas pela classificação de LeRoy em três formas: cutânea difusa (n = 5), cutânea limitada (n = 11) e limitada (n = 3), com um período de seguimento com uma duração mediana de 5, 12 e 6 anos, respetivamente. O fenómeno de Raynaud e as anomalias nos capilares peri-ungueais estavam presentes em todas as doentes. Todas as doentes com a forma difusa apresentavam doença intersticial pulmonar, ausente na forma cutânea limitada. As pitting scars foram mais frequentes na forma difusa. A doença ativa foi mais frequente na forma difusa, na sua maioria tratada com antagonistas dos recetores da endotelina. Num período de 21 anos (de 1994 a 2015), a mortalidade foi de 55% (n = 23/42). A expectativa de vida nos doentes com a forma difusa estava significativamente reduzida quando comparada com a forma localizada. Discussão: O nosso grupo de doentes é semelhante a outros de maiores dimensões e cariz internacional e, mais especificamente, enquadra-se nas características dos doentes registados nos registos Scleroderma Trials and Research group. Conclusão: O registo Scleroderma Trials and Research group incentivou uma caracterização sistemática e pode revelar-se um veículo para a criação de registos mais homogéneos.

Utilization of residues from agro-forest industries in the production of high value bacterial cellulose.

Bacterial cellulose (BC), a very peculiar form of cellulose, is gaining considerable importance due to its unique properties. In this study, several residues, from agro-forestry industries, namely grape skins aqueous extract, cheese whey, crude glycerol and sulfite pulping liquor were evaluated as economic carbon and nutrient sources for the production of BC. The most relevant BC amounts attained with the residues from the wine and pulp industries were 0.6 and 0.3 g/L, respectively, followed by biodiesel crude residue and cheese whey with productions of about, 0.1 g/L after 96 h of incubation. Preliminary results on the addition of other nutrient sources (yeast extract, nitrogen and phosphate) to the residues-based culture media indicated that, in general, these BC productions could be increased by ~200% and ~100% for the crude glycerol and grape skins, respectively, after the addition organic or inorganic nitrogen.