Intravitreal anti-VEGF therapy for choroidal neovascularisation secondary to pathological myopia: 4-year outcome

OBJECTIVE: To report the visual outcome after 4-year follow-up in a series of highly myopic eyes with choroidal neovascularisation (CNV) treated with antivascular endothelial growth factor (anti-VEGF) drugs. METHODS: A retrospective, non-randomised, multicentre, consecutive, interventional case series study was performed. 92 highly myopic eyes with subfoveal CNV were treated with intravitreal injection (IVI) of anti-VEGF. The initial protocol (1 vs 3 injections) was dictated by surgeons' preferences and followed by an as-needed monthly regime. Best-corrected visual acuity (BCVA) was evaluated at baseline and then monthly. The primary aim was to analyse BCVA changes. The effect of age, spherical equivalent (SE) and treating drug were evaluated as secondary objectives. RESULTS: The mean age of the patients was 57 years (SD 14, range 30-93). The mean number of letters read was 46.1 (SD 16.8, range 5-70) at baseline, 55.5 (SD 18.6, range 10-85) at 12 months, 50.1 (SD 20.1, range 5-82) at 24 months, 54.2 (SD 21.9, range 2-85) at 36 months and 53.1 (SD 22.5, range 1-83) at 48 months (p=0.000, initial vs 12, 24 and 36 months; p=0.01 initial vs 48 months; Student t test for paired data). The mean total number of IVI was 4.9 (SD 5.4, range 1-29). SE and treating drug had no influence on the final visual outcome and number of injections required. CONCLUSIONS: Intravitreal bevacizumab and ranibizumab are effective therapies and show similar clinical effects in highly myopic CNV. Visual acuity gain is maintained at 4-year follow-up

A framework for group decision-making: Including cognitive and affective aspects in a MCDA method for alternatives rejection

© Springer International Publishing AG, part of Springer Nature 2019. With the evolution of the organizations and technology, Group Decision Support Systems have changed to support decision-makers that cannot be together at the same place and time to make a decision. However, these systems must now be able to support the interaction between decision-makers and provide all the relevant information at the most adequate times. Failing to do so may compromise the success and the acceptance of the system. In this work it is proposed a framework for group decision using a Multiple Criteria Decision Analysis method capable of identify inconsistent assessments done by the decision-maker and identify alternatives that should be rejected by the group of decision-makers. The proposed framework allows to present more relevant information throughout the decision-making process and this way guide decision-makers in the achievement of more consensual and satisfactory decisions.INCT-EN - Instituto Nacional de Ciência e Tecnologia para Excitotoxicidade e Neuroproteção(ANI|P2020 21958

Intramural Vesical Leiomyoma in a Patient with a Pelvic Fibrous Tumour - Case Report

Introdução: O leiomioma vesical é um tumor benigno raro que representa,aproximadamente, 0,5% do total de neoplasias da bexiga. É frequentemente um achado imagiológico, sendo a sua localização e dimensões determinantes no desenvolvimento de sintomatologia e no tipo de procedimento a efectuar. Caso Clínico: Reporta-se o caso de um doente com queixas urinárias de disúria, polaquiúria e esforço miccional, inicialmente interpretadas como HBP. A investigação diagnóstica culminou com a enucleação de uma volumosa massa intramural da bexiga, com diagnóstico histológico de leiomioma, num doente com antecedentes de doença de Madelung e excisão prévia de um tumor fibroso paravesical. Discussão: O leiomioma vesical, embora apresentando características imagiológicas típicas, deve ser sempre biopsado para confirmação histológica da sua etiologia. O tumor fibroso pélvico apresenta sempre indicação cirúrgica pois, numa minoria de casos, pode apresentar comportamento agressivo com infiltração dos órgãos adjacentes

The adaptive immune landscape of the colorectal adenoma–carcinoma sequence

Background. The tumor immune microenvironment exerts a pivotal influence in tumor initiation and progression. The aim of this study was to analyze the immune context of sporadic and familial adenomatous polyposis (FAP) lesions along the colorectal adenoma–carcinoma sequence (ACS). Methods. We analyzed immune cell counts (CD3+, CD4+, CD8+, Foxp3+, and CD57+), tumor mutation burden (TMB), MHC-I expression and PD-L1 expression of 59 FAP and 74 sporadic colorectal lesions, encompassing adenomas with low-grade dysplasia (LGD) (30 FAP; 30 sporadic), adenomas with high-grade dysplasia (22 FAP; 30 sporadic), and invasive adenocarcinomas (7 FAP; 14 sporadic). Results. The sporadic colorectal ACS was characterized by (1) a stepwise decrease in immune cell counts, (2) an increase in TMB and MHC-I expression, and (3) a lower PD-L1 expression. In FAP lesions, we observed the same patterns, except for an increase in TMB along the ACS. FAP LGD lesions harbored lower Foxp3+ T cell counts than sporadic LGD lesions. A decrease in PD-L1 expression occurred earlier in FAP lesions compared to sporadic ones. Conclusions. The colorectal ACS is characterized by a progressive loss of adaptive immune infiltrate and by the establishment of a progressively immune cold microenvironment. These changes do not appear to be related with the loss of immunogenicity of tumor cells, or to the onset of an immunosuppressive tumor microenvironment.This research was funded by FEDER—Fundo Europeu de Desenvolvimento Regional funds through the COMPETE 2020-Operational Programme for Competitiveness and Internationalisation (POCI), Portugal 2020, and by FCT-Fundação para a Ciência e a Tecnologia/Ministério da Ciência, Tecnologia e Inovação in the framework of the projects “Institute for Research and Innovation in Health Sciences” (POCI-01-0145-FEDER-007274), and “O papel dos Tregs na resposta imune ao cancro” (PTDC/MED-PAT/32462/2017)

Plasma glucose regulation and insulin secretion in hypertriglyceridemic mice

In this study, we examined glucose homeostasis and insulin secretion in transgenic mice overexpressing the human apolipoprotein CIII gene (apo CIII tg). These mice have elevated plasma levels of triglycerides, FFA and cholesterol compared to control mice. The body weight, plasma glucose, and insulin levels, glucose disappearance rates, areas under the ipGTT curve for adult (4-8 mo. old) and aged (20-24 mo. old) apo CIII tg mice and the determination of insulin during the ipGTT were riot different from those of control mice. However, an additional elevation of plasma FFA by treatment with heparin for 2-4h impaired the ipGTT responses in apo CIII tg mice compared to saline-treated mice. The glucose disappearance rate in heparin-treated transgenic mice was slightly lower than in heparin-treated controls. Glucose (22.2 mmol/l) stimulated insulin secretion in isolated islets to the same extent in saline-treated control and apo CIII tg mice. in islets from heparin-treated apo CIII tg mice, the insulin secretion at 2.8 and 22.2 mmol glucose/l was lower than in heparin-treated control mice. In conclusion, hypertriglyceridemia per se or a mild elevation in FFA did not affect insulin secretion or insulin resistance in adult or aged apo CIII tg mice. Nonetheless, an additional elevation of FFA induced by heparin in hypertriglyceridemic mice impaired the ipGTT by reducing insulin secretion.341212

Predictability of evolutionary trajectories in fitness landscapes

Experimental studies on enzyme evolution show that only a small fraction of all possible mutation trajectories are accessible to evolution. However, these experiments deal with individual enzymes and explore a tiny part of the fitness landscape. We report an exhaustive analysis of fitness landscapes constructed with an off-lattice model of protein folding where fitness is equated with robustness to misfolding. This model mimics the essential features of the interactions between amino acids, is consistent with the key paradigms of protein folding and reproduces the universal distribution of evolutionary rates among orthologous proteins. We introduce mean path divergence as a quantitative measure of the degree to which the starting and ending points determine the path of evolution in fitness landscapes. Global measures of landscape roughness are good predictors of path divergence in all studied landscapes: the mean path divergence is greater in smooth landscapes than in rough ones. The model-derived and experimental landscapes are significantly smoother than random landscapes and resemble additive landscapes perturbed with moderate amounts of noise; thus, these landscapes are substantially robust to mutation. The model landscapes show a deficit of suboptimal peaks even compared with noisy additive landscapes with similar overall roughness. We suggest that smoothness and the substantial deficit of peaks in the fitness landscapes of protein evolution are fundamental consequences of the physics of protein folding.Comment: 14 pages, 7 figure

Synthesis of iron-doped TiO2 nanoparticles by ball-milling process : the influence of process parameters on the structural, optical, magnetic, and photocatalytic properties

Titanium dioxide (TiO2) absorbs only a small fraction of incoming sunlight in the visible region thus limiting its photocatalytic efficiency and concomitant photocatalytic ability. The large-scale application of TiO2 nanoparticles has been limited due to the need of using an ultraviolet excitation source to achieve high photocatalytic activity. The inclusion of foreign chemical elements in the TiO2 lattice can tune its band gap resulting in an absorption edge red-shifted to lower energies enhancing the photocatalytic performance in the visible region of the electromagnetic spectrum. In this research work, TiO2 nanoparticles were doped with iron powder in a planetary ball-milling system using stainless steel balls. The correlation between milling rotation speeds with structural and morphologic characteristics, optical and magnetic properties, and photocatalytic abilities of bare and Fedoped TiO2 powders was studied and discussed.This work was partially financed by FCT-Fundacao para a Ciencia e Tecnologia-under the project PTDC/FIS/120412/2010: "Nanobased concepts for Innovative & Eco-sustainable constructive material's surfaces.

Psoriatic Arthritis and Burden of Disease: Patient Perspectives from the Population-Based Multinational Assessment of Psoriasis and Psoriatic Arthritis (MAPP) Survey

Introduction: Psoriatic arthritis (PsA) is underdiagnosed and has a substantial impact on quality of life, disability, and work productivity. The population-based Multinational Assessment of Psoriasis and Psoriatic Arthritis (MAPP) survey examined the impact of PsA on patients’ activities of daily living and unmet treatment needs. Methods: This large-scale, random digit dialing, telephone survey of patients self-reporting a diagnosis of psoriasis and/or PsA was conducted in North America and Europe. Results: In all, 3426 patients participated in the survey, including 712 (21%) who identified themselves as having PsA. Over half of the patients reported severe PsA involving more than four joints. Eighty-three percent of patients with PsA visited a health-care provider within the past 12 months. Approximately one-quarter saw their primary care provider or dermatologist most often for their disease; 37% responded that their rheumatologist was the health-care provider seen most often for PsA. Patients with PsA reported a substantial impact of disease on physical function. One-third of patients with PsA reported missing work because of their disease and PsA impacted their ability to work full time. Over half of the patients with PsA (58%) reported receiving no treatment or topical therapy only, leaving their joint disease untreated. Factors associated with lack of adherence were perceived lack of efficacy and concerns about long-term safety. Conclusions: The MAPP survey confirms that PsA has a significant impact on physical function and activities of daily living. Undertreatment of PsA suggests a need for improved screening and diagnosis as well as education about treatment options and adherence