Diet as a modulator of intestinal microbiota in rheumatoid arthritis

© 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/)Rheumatoid arthritis (RA) is a chronic immune-driven inflammatory disease characterised by synovial inflammation, leading to progressive cartilage and bone destruction, impacting patients’ functional capacity and quality of life. Patients with RA have significant differences in gut microbiota composition when compared to controls. Intestinal dysbiosis influences the intestinal barrier strength, integrity and function, and diet is considered the main environmental factor impacting gut microbiota. Over the last few years, researchers have focused on the influence of single components of the diet in the modulation of intestinal microbiota in RA rather than whole dietary patterns. In this review, we focus on how the Mediterranean diet (MD), a whole dietary pattern, could possibly act as an adjuvant therapeutic approach, modulating intestinal microbiota and intestinal barrier function in order to improve RA-related outcomes. We also review the potential effects of particular components of the MD, such as n-3 polyunsaturated fatty acids (PUFAs), polyphenols and fibre.info:eu-repo/semantics/publishedVersio

Computer simulations of adsorption and molecular recognition phenomena in molecularly imprinted polymers

Molecularly imprinted polymers (MIPs) are a novel, promising family of porous materials with potential applications ranging from separations, chemical sensing and catalysis to drug delivery and artificial immunoassays. The unique feature of these materials is their biomimetic molecular recognition functionality. Molecular recognition is the biological phenomenon of specific, selective and strong association between a substrate and a ligand. In man made MIPs this functionality is implemented via templated synthesis protocol. MIPs are synthesized in the presence of additional template molecules which form complexes with functional monomers in the pre‐polymerization mixture. After polymerization, the template is removed, leaving cavities in the structure which are complementary in shape and interaction patterns to the template molecules. These cavities act as mimics of biological receptors and are able to recognize and rebind template molecules. Although the imprinting concept is simple in principle, synthesis of MIPs with precisely controlled characteristics and performance remains a challenging task. Composition, polymerization conditions, template removal process and application conditions all affect the properties of MIPs. The material is affected at different scales, but crucially at the microscopic level, the number, fidelity and accessibility of binding sites are dependent on all the factors mentioned. The full potential of these materials can only be achieved if researchers can control and optimize the properties of MIPs through detailed understanding of adsorption and molecular recognition processes in these materials. The objective of this work is to, using computer simulations and statistical mechanics; develop a fundamental description of MIP formation and function, and to link morphological features of the model materials to their molecular recognition capabilities. In general, molecular simulations employed in this study should allow easier and more efficient exploration of a vast number of factors influencing the behaviour of MIPs. At the heart of the approach developed in this thesis is a computational strategy that imitates all the stages of MIP formation and function. First, the model simulates the pre‐polymerization mixture, allowing the formation of template‐functional monomer complexes. (This stage is implemented via canonical Monte Carlo simulation). Complexes can have different structures, depending on the chemical nature of template and functional monomer; therefore complexes can have a range of association constants. The distribution of template‐functional monomer complexes also translates into a distribution of binding sites of different specificity after template removal. In the second stage of the process, adsorption simulations (grand canonical Monte Carlo) are performed for a variety of model MIPs prepared to assess the role of various processing conditions such as composition, density and binding sites degeneration. This strategy was first applied to a simplified description of MIP species in order to identify the minimal model capable of molecular recognition and thus shed the light on the very nature of this phenomenon. In the developed model, the molecular species are constructed from hard spheres, featuring small interaction sites on their surfaces. The bond between two interaction sites has the strength and topological features of a typical hydrogen bond. The model exhibits molecular recognition, being able to preferentially adsorb template molecules. The associations between template and functional monomers were analyzed and classified to describe the distribution of binding sites and their heterogeneity. Using this model, several experimental trends typically observed in MIP studies could be explained, such as maximum in the selectivity as a function of monomer concentration. Using this model, we were also able to explore hypothetical, alternative protocols for MIP synthesis in order to improve their performance. These include the use of alternative templates and the post‐synthetic surface modifications of MIPs. The general strategy to modelling MIP, employed in this thesis, was then applied to a more detailed description of MIPs with realistic force field potentials for all the species involved. This more elaborate model is simulated with a combination of molecular dynamics (MD) and Monte Carlo techniques. This detailed model provided a wealth of information on various types of complexes observed in the pre‐polymerization mixture. Specifically, it revealed the relative weight of different interactions in the complex and their role in the binding energy of adsorbates. These simulations also provided the comparison of the relative contribution of different types of interactions (van der Waals, Coulombic) involved in a molecular recognition process. We believe the insights gained in this work will contribute to the development of rational MIP design strategies. In the discussion of the results of the thesis we speculate on how these models can be further developed in order to generate quantitative predictions and what type of systems it would be interesting and important to investigate in the future

Probiotic supplementation for Rheumatoid Arthritis: a promising adjuvant therapy in the gut microbiome era

Copyright © 2021 Ferro, Charneca, Dourado, Guerreiro and Fonseca. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.Rheumatoid arthritis (RA) is a chronic immune-mediated inflammatory disease that ultimately leads to joint destruction and functional disability. Although the exact etiology of RA is not fully understood, it is well established that gut microbiota (GM) plays a vital role in the pathogenesis of RA, with accumulating evidence suggesting that gut dysbiosis induces a chronic inflammatory response that may be linked to disease development. Of interest, patients with RA have significant changes in the intestinal microbiota compared to healthy controls, and several studies have suggested the use of probiotics as a possible adjuvant therapy for RA. Benefits of probiotic supplementation were reported in animal models of arthritis and human studies, but the current evidence regarding the effect of probiotic supplementation in the management of RA remains insufficient to make definite recommendations. Several different strains of Lactobacillus and Bifidobacteria, as single species or in mixed culture, have been investigated, and some have demonstrated beneficial effects on disease activity in RA human subjects. As of now, L.casei probiotic bacteria seems to be the strongest candidate for application as adjuvant therapy for RA patients. In this review, we highlight the role of GM in the development and progression of RA and summarize the current knowledge on the use of probiotics as a potential adjuvant therapy for RA. We also review the proposed mechanisms whereby probiotics regulate inflammation. Finally, the role of fermented foods is discussed as a possible alternative to probiotic supplements since they have also been reported to have health benefits.info:eu-repo/semantics/publishedVersio

The safety and persistence of intravenous iloprost in systemic sclerosis

© Sociedade Portuguesa de ReumatologiaIntroduction: Vasculopathy is a crucial feature of systemic sclerosis (SSc). It occurs in almost every patient with SSc, with Raynaud's phenomenon (RP) and digital ulcers (DU) having a great impact on the quality of patients' lives. Intravenous (IV) iloprost, a synthetic analogue of prostacyclin, is broadly used to treat RP and DU secondary to SSc. Currently, there is no standard protocol defined for the iloprost treatment of SSc-associated RP and DU, and, consequently, the management of this treatment is largely based on each centre's experience. Objective: The objective of this study is to evaluate the safety profile of a particular scheme of IV iloprost used in our centre as the standard treatment of SSc-related vascular complications. Methods: We retrospectively evaluated the clinical records of SSc patients, classified according to the 2013 European Alliance of Associations for Rheumatology (EULAR) criteria (31) with SSc-related DU and/or severe RP not responsive to CCB, receiving or who have received IV iloprost infusions from January 1st 2011 to March 31st 2021 Results: Within this time frame, 60 patients (n=44 for DU; n=16 for severe RP) were treated with a monthly 10-hour IV iloprost perfusion with a dosing regimen adapted to individual tolerance. Forty-nine of these 60 patients (81.7%) were on iloprost for more than one year. Within 12 months of therapy, 40 patients have healed the DUs (90.9%), with only 4 patients maintaining active DUs. A significant clinical improvement in RP at 12 months was observed in 87.5% (n=14/16) of SSc patients with severe RP. Eleven AE implying treatment dose/frequency adjustments or suspension were recorded (18.3% of patients): severe headache (n=5), hypotension (n=3), tachycardia (n=1), flushing (n=1) and generalised erythroderma (n=1). In all patients, the perfusion rate was reduced in the following treatment sessions with good tolerance, with the exception of the patient with the generalised erythroderma reaction, who suspended the perfusion and was later switched to bosentan. After a mean follow-up time of 6.9 (+/-) 4.0 years of treatment (range 0.06-22), 24 patients (40%) stopped the therapy, 14 (58.3%) of whom due to clinical improvement. The overall 5-, and 10-year survival rates of IV iloprost were 68.2% and 55.6%, respectively. Conclusion: SSc patients who received this flexible IV iloprost regimen achieved clinical improvement, reflected in the high persistence rate of the drug, with a good tolerability profile. In addition, most side effects were mild and easily managed.info:eu-repo/semantics/publishedVersio

SÍNDROME DE STEVENS-JOHNSON: UMA REVISÃO BIBLIOGRÁFICA

Stevens-Johnson syndrome is a disease with a wide presentation of clinical manifestations, due not only to acute mucocutaneous reactions, but also to systemic manifestations that can evolve to a potential fatality. In this sense, this chapter reviews not only the main aspects of this pathology, such as definition, etiology, epidemiology and specific pathophysiology, but also in the same way, diagnosis, treatment principles and possible prognoses.El síndrome de Stevens-Johnson es una enfermedad con una amplia presentación de manifestaciones clínicas, debido no solo a reacciones mucocutáneas agudas, sino también a manifestaciones sistémicas que pueden evolucionar a una muerte potencial. En este sentido, este capítulo revisa no sólo los aspectos principales de esta patología, como la definición, la etiología, la epidemiología y la fisiopatología específica, sino también, de la misma manera, el diagnóstico, los principios de tratamiento y los posibles pronósticos.A Síndrome de Stevens-Johnson é uma doença com ampla apresentação de manifestações clínicas, devido não somente ao quadro de reações mucocutâneas agudas, mas também a manifestações sistêmicas que podem evoluir para uma potencial fatalidade. Nesse sentido, esse capítulo revisa não somente os principais aspectos desta patologia, como definição, etiologia, epidemiologia e a fisiopatologia específica, mas também de igual forma, diagnóstico, princípios de tratamento e possíveis prognósticos.A Síndrome de Stevens-Johnson é uma doença com ampla apresentação de manifestações clínicas, devido não somente ao quadro de reações mucocutâneas agudas, mas também a manifestações sistêmicas que podem evoluir para uma potencial fatalidade. Nesse sentido, esse capítulo revisa não somente os principais aspectos desta patologia, como definição, etiologia, epidemiologia e a fisiopatologia específica, mas também de igual forma, diagnóstico, princípios de tratamento e possíveis prognósticos

Ten years of a systemic sclerosis clinic in a tertiary referral centre - insights and future directions

© Sociedade Portuguesa de ReumatologiaSystemic sclerosis (SSc) is an uncommon condition, with a wide range of manifestations, characterized by specific antibody production, vasculopathy and fibrosis of the skin and other internal organs. It is a complex disease, which is estimated to be rare in Portugal, although specific incidence data are missing. The aetiology of SSc remains unknown, but is likely to be multifactorial, involving genetic and environmental aspects. Its management is challenging and often requires a multidisciplinary approach. In 2011, we established a dedicated outpatient clinic for patients with SSc. Clinical data of every patient with a confirmed diagnosis of SSc is prospectively registered in Reuma.pt/SSc. In this manuscript, we aim to describe the general functioning of our SSc outpatient clinic, and to characterise the population of patients with SSc who are followed herein.info:eu-repo/semantics/publishedVersio

Simulações e Modelagem Hidrológica de Microbacia Urbana para Previsão de Inundações: o caso do rio das Antas na cidade de Anápolis-GO

The study area is located along the Rio das Antas basin in the city of Anápolis, Goiás. This study exemplifies an urban area exposed to flooding by rainwater. Decline in the permeability of the river basin area is result of significant real state development in recent years. This study proposes to simulate water flows and respective flooding areas along different sections of the River in response to different rainfall intensities. The simulated flow rates are the result of interpretation of land use scenarios and hydrologic modeling of the river basin area. The rational method and the Bernoulli equation were used in the hydraulic simulation model of the computer program HEC-RAS (Hydrologic Engineering Center's River Analysis System)...Este estudo se propõe a simular as diferentes vazões do rio das Antas em trechos distintos e de suas respectivas áreas de inundação, em resposta às diferentes intensidades de chuva. A porção estudada da bacia do Rio das Antas está localizada na cidade de Anápolis, no Centro-Oeste goiano. O caso estudado exemplifica uma área urbana com riscos de inundação e alagamento pelas águas pluviais. A cidade encontra-se em franca expansão urbana, o que tem provocado, como consequência, o incremento da impermeabilização da bacia estudada. Essas vazões simuladas foram construídas a partir da interpretação do uso e da ocupação do solo na bacia em foco utilizando modelagem hidrológica por meio do método Racional e da equação de Bernoulli, no modelo de simulação hidráulica do programa computacional HEC-RAS (Hydrologic Enginnering Center’s River Analisys System)..

Galerkin projected residual method applied to diffusion–reaction problems

A stabilized finite element method is presented for scalar and linear second-order boundary value problems. The method is obtained by adding to the Galerkin formulation multiple projections of the residual of the differential equation at element level. These multiple projections allow the generation of appropriate number of free stabilization parameters in the element matrix depending on the local space of approximation and on the differential operator. The free parameters can be determined imposing some convergence and/or stability criteria or by postulating the element matrix with the desired stability properties. The element matrix of most stabilized methods (such as, GLS and GGLS methods) can be obtained using this new method with appropriate choices of the stabilization parameters. We applied this formulation to diffusion–reaction problems. Optimal rates of convergency are numerically observed for regular solutions.Indisponível

A nearly optimal Galerkin projected residual finite element method for Helmholtz problem

A Finite Element Formulation for scalar and linear second-order boundary value problems is introduced. The new method relies on a variational formulation obtained following the usual path of appending to the Galerkin variational formulation, a balanced residual form of the governing partial differential equation computed within each element. The novelty consists of projecting the residual in a subspace defined for each element, which gives rise to the name of the method: Galerkin Projected Residual (GPR). This subspace is built by systematically exploring some a priori criteria (either based on the physics or on the underlying mathematics). The method can be used to stabilize a variety of problems. Here it is applied to Helmholtz equation, where standard Galerkin formulations are known to present poor approximations for high wave numbers. The method is formally introduced along with some numerical examples that are used to assess the improvements achieved.Indisponível