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Online ahead of print; International audience; Introduction: It is important to confirm the effectiveness and tolerability of disease-modifying treatments for relapsing-remitting multiple sclerosis (RRMS) in real-world treatment settings. This prospective observational cohort study (VIRGILE) was performed at the request of the French health authorities. The primary objective was to evaluate the effectiveness of fingolimod 0.5 mg in reducing the annualised relapse rate (ARR) in patients with RRMS.Methods: Participating neurologists enrolled all adult patients with RRMS starting fingolimod treatment between 2014 and 2016, who were followed for 3 years. Follow-up consultations took place at the investigator's discretion. The primary outcome measure was the change in ARR at month 24 after fingolimod initiation. Relapses and adverse events were documented at each consultation; disability assessment (EDSS) and magnetic resonance imagery were performed at the investigator's discretion.Results: Of 1055 eligible patients, 633 patients were assessable at month 36; 405 (64.0%) were treated continuously with fingolimod for 3 years. The ARR decreased from 0.92 ± 0.92 at inclusion to 0.31 ± 0.51 at month 24, a significant reduction of 0.58 [95% CI - 0.51 to - 0.65] relapses/year (p < 0.001). Since starting fingolimod, 461 patients (60.9%) remained relapse-free at month 24 and 366 patients (55.5%) at month 36. In multivariate analysis, no previous disease-modifying treatment, number of relapses in the previous year and lower EDSS score at inclusion were associated with a greater on-treatment reduction in ARR. The mean EDSS score remained stable over the course of the study. Sixty-one out of 289 (21.1%) patients presented new radiological signs of disease activity. Treatment-related serious adverse events were lymphopenia (N = 21), bradycardia (N = 19), elevated transaminases (N = 9) and macular oedema (N = 9).Conclusions: The effectiveness and tolerability of fingolimod in everyday clinical practice are consistent with findings of previous phase III studies. Our study highlights the utility of fingolimod for the long-term management of patients with multiple sclerosis.

Physical activity and exercise are different constructs. However, professionals usually employ heterogeneous definitions for these distinct constructs, resulting in nonspecific and inaccurate assessments, which compromise clinical decision making.The aim of this study was to verify if the levels of physical activity behave similarly between individuals with stroke and healthy-control individuals with the same levels of exercise.Seventy-five stroke survivors and 75 healthy-control individuals matched by levels of exercise, age, and sex were evaluated. The level of exercise was classified as inactive, insufficient, and moderate/vigorous according to the Centers for Disease Control and Prevention criteria. The level of physical activity was assessed with the Human Activity Profile (HAP) and classified as "inactive," "moderately active," and "active." The physical activity level was compared between groups of subjects (stroke versus healthy-control) and subgroups of the level of exercise ("inactive," "insufficient," and "moderate/vigorous" level of exercise) (α = 5%).Stroke survivors had a significantly lower level of physical activity (HAP: 51 ± 22 and 71 ± 19 points, respectively). Only for individuals with stroke, a statistically significant difference was found in the levels of physical activity between subgroups of level of exercise, specifically between "inactive" and "moderate/vigorous" subgroups (HAP:47 ± 22 and 70 ± 8 points, respectively).Physical activity behaved differently between individuals with stroke and healthy-control individuals with the same levels of exercise. Individuals with stroke had worse physical activity levels than matched controls. Furthermore, different from individuals with stroke, in healthy-control individuals with different levels of exercise, the level of physical activity was similar.

The dynamical system described herein uses a hybrid cellular automata (CA) mechanism to attain reversibility, and this approach is adapted to create a novel block cipher algorithm called HCA. CA are widely used for modeling complex systems and employ an inherently parallel model. Therefore, applications derived from CA have a tendency to fit very well in the current computational paradigm where scalability and multi-threading potential are quite desirable characteristics. HCA model has recently received a patent by the Brazilian agency INPI. Several evaluations and analyses performed on the model are presented here, such as theoretical discussions related to its reversibility and an analysis based on graph theory, which reduces HCA security to the well-known Hamiltonian cycle problem that belongs to the NP-complete class. Finally, the cryptographic robustness of HCA is empirically evaluated through several tests, including avalanche property compliance and the NIST randomness suite., 34 pages, 12 figures

Natural Killer cells are innate lymphocytes with central roles in immunosurveillance and are implicated in autoimmune pathogenesis. The degree to which regulatory variants affect Natural Killer cell gene expression is poorly understood. Here we perform expression quantitative trait locus mapping of negatively selected Natural Killer cells from a population of healthy Europeans (n = 245). We find a significant subset of genes demonstrate expression quantitative trait loci specific to Natural Killer cells and these are highly informative of human disease, in particular autoimmunity. A Natural Killer cell transcriptome-wide association study across five common autoimmune diseases identifies further novel associations at 27 genes. In addition to these cis observations, we find novel master-regulatory regions impacting expression of trans gene networks at regions including 19q13.4, the Killer cell Immunoglobulin-like Receptor region, GNLY, MC1R and UVSSA. Our findings provide new insights into the unique biology of Natural Killer cells, demonstrating markedly different expression quantitative trait loci from other immune cells, with implications for disease mechanisms.

This work explored the use of ozonation and photoperoxidation before the microfiltration process to reduce fouling. Produced water was synthesized with salt, viscosifier, and surfactant. The additives influence on membrane fouling was evaluated. Photoperoxidation process led to an overall better performance than ozonation in terms of oil removal and fouling reduction. The maximum oil removal efficiency was 86%, obtained for emulsions with salt after 2 h of treatment (COD: H2O2 ratio 1:1, UV dose of 965 J/m2). The inclusion of chemical additives impaired the oxidative power of hydroxyl radicals leading to a moderate oil removal; however, they were still able to reduce membrane fouling, mainly in oil/water emulsions with viscosifier. Higher salt concentration promoted fouling resistance and also benefited the permeate quality. Cross-flow microfiltration process integrated with photoperoxidation was able to improve the permeate flux from 84 to 182 L/m2.h after 3 h of exposure to UV radiation, resulting in a permeate with less than 10 mg/L of oil content.

The aim of this study was to evaluate the structure of soil bacterial and fungal communities in restinga areas of the Atlantic Forest (southern Brazil) after the introduction of Pinus L. Soil samples were collected in the 0–10 cm depth from two arboreal (FR-restinga subject to flooding and DR-dry restinga) and one herbaceous (MR-restinga under marine influence) areas. In addition to these areas, soil samples were collected from FR and DR under the influence of Pinus sp. (FRPinus and DRPinus, respectively), as reference areas. The structure of bacterial and fungal communities was evaluated by PCR-DGGE. Notably, a reduction in the number of amplicons was observed in areas with presence of Pinus sp. In conclusion, the present manuscript highlighted that the allochthonous tree species (Pinus sp.) has a deleterious impact on soil microbes and affects the growth of natural vegetation in a conservation unit in the Atlantic Forest of the Southern Brazilian coast.

Vulcanized residues of ethylene–propylene–diene monomer rubber (EPDM) from expanded profiles trims, called EPDM-r, were treated to remove the paraffinic oil and then devulcanized by microwaves at different exposure times (0, 2, 3 and 4 min). Elastomeric formulations of EPDM-r compound/raw EPDM compound containing 67 wt% of recycled phase were produced, and the characteristics of the vulcanization process, mechanical and dynamic-mechanical properties, morphology and accelerated aging of the blends were analyzed. The promising results showed that it is possible to obtain new rubber compositions containing 67 wt% of EPDM-r with similar—or even higher—mechanical properties than the Reference sample (without EPDM-r), pointing out to the potential use of devulcanized EPDM-r in several applications, as a possible solution to the destination of these materials, aiming at the sustainable development.

1,3-Dimethylamylamine (DMAA) is known to be added to dietary supplements from synthetic sources and, presumably, from natural geranium oil. However, the natural occurrence of DMAA in geranium oil (Pelargonium graveolens) has been controversial as published studies report contradicting findings. It is unclear if the difference in detection of DMMA in Pelargonium species is a result of the loss during extraction methods, different detection capabilities of analytical methods or if the content of DMAA is dependent of the species and geographical origins. Consequently, the purpose of this study is threefold: (1) to compare the analytical performance of mass spectrometry methods for the detection of DMMA, including GC/MS, DART–MS/MS and LC–MS/MS; (2) to evaluate if DMMA is lost during the extraction of essential oils from Pelargonium leaves of species from Brazil testing headspace extraction, and (3) to evaluate if DMMA is naturally present in a variety of essential oils originating from six countries. This study shows that for detection of more volatile compounds, headspace GC–MS proved to be more favorable than hydrodistilled essential oil analyzed by direct injection in GC–MS. DART–MS/MS showed to be a good alternative for identification of essential oils compounds and DMAA without sample preparation; LC–MS/MS proved to be sensitive for DMMA identification. Nevertheless, even after the analysis using mentioned methods, all essential oils and for the first time, the volatile components extracted from leaves, showed to be absent of DMAA, proving that its presence is not natural in these species.

Around the world women end up being less interested in areas related to the sciences, technology, engineering and mathematics, or shortly STEM. Therefore, it is important that governments around the world maintain an active interest in getting women to continue in STEM careers. In this context, this work was divided into three main phases, the first was to conduct a search through a related works that were published involving the development of projects aimed at the engagement of girls students or female teachers/professionals within the context of STEM or Robotics, between the years 2018 and 2020. In this case, seven works were found within these criteria, including one Brazilian project. Subsequently, analyzes were carried out of the 85 projects that are being financed by the federal government of Brazil within STEM. The last analysis was a case study to evaluate the engagement of female teachers and students in a medium-sized city in the interior of the southeastern region of Brazil. In this case, we carried out the analysis with the teachers and students, as well as with an external audience. We carry out our analyzes through statistics and analysis of feelings and opinions, in addition to data visualizations. In the end, we conducted through data mining of unsupervised machine learning, analyzes of the groups of people we are interested in engaging, which are groups of young people, especially girls who are interested in STEM, but with little knowledge in Robotics. This strategy was put on the schedule, because we will aim to increase the knowledge of these girls in STEM, especially in robotics, which is the focus of our study and research group. Finally, results have shown that this project has improved a major social and encouraging role for these girls in the field of exact sciences, computing and engineering.

The generation of information, energy and biomass in living cells involves integrated processes that optimally evolve into complex and robust cellular networks. Protein homo-oligomerization, which is correlated with cooperativity in biology, is one means of scaling the complexity of protein networks. It can play critical roles in determining the sensitivity of genetic regulatory circuits and metabolic pathways. Therefore, understanding the roles of oligomerization may lead to new approaches of probing biological functions. Here, we analyzed the frequency of protein oligomerization degree in the cell proteome of nine different organisms, and then, we asked whether there are design trade-offs between protein oligomerization, information precision and energy costs of protein synthesis. Our results indicate that there is an upper limit for the degree of protein oligomerization, possibly because of the trade-off between cellular resource limitations and the information precision involved in biochemical reaction networks. These findings can explain the principles of cellular architecture design and provide a quantitative tool to scale synthetic biological systems.

The generation of information, energy and biomass in living cells involves integrated processes that optimally evolve into complex and robust cellular networks. Protein homo-oligomerization, which is correlated with cooperativity in biology, is one means of scaling the complexity of protein networks. It can play critical roles in determining the sensitivity of genetic regulatory circuits and metabolic pathways. Therefore, understanding the roles of oligomerization may lead to new approaches of probing biological functions. Here, we analyzed the frequency of protein oligomerization degree in the cell proteome of nine different organisms, and then, we asked whether there are design trade-offs between protein oligomerization, information precision and energy costs of protein synthesis. Our results indicate that there is an upper limit for the degree of protein oligomerization, possibly because of the trade-off between cellular resource limitations and the information precision involved in biochemical reaction networks. These findings can explain the principles of cellular architecture design and provide a quantitative tool to scale synthetic biological systems.

The Registries of Bone Marrow Donors around the world include more than 30 million volunteer donors from 57 different countries, and were responsible for over 17,000 hematopoietic stem cell transplants in 2016. The Brazilian Bone Marrow Volunteer Donor Registry (REDOME) was established in 1993 and is the third largest registry in the world with more than 4.3 million donors. We characterized HLA allele and haplotypes frequencies from REDOME comparing them with the donor self-reported race group classification. Five-locus haplotype frequencies (A~C~B~DRB1~DQB1) were estimated for each of the six race groups, resolving phase and allelic ambiguity using the expectation-maximization (EM) algorithm. The top 100 haplotypes in the race groups were separated into eight clusters of haplotypes, based on haplotype similarity, using CLUTO. We present HLA allele and haplotype frequency data from six race groups from 2,938,259 individuals from REDOME. The most frequent haplotype was the same for all groups: A*01:01g~C*07:01g~B*08:01g~DRB1*03:01g~DQB1*02:01g. Some frequent haplotypes such as A*02:01g~C*16:01g~B*44:03~DRB1*07:01g~DQB1*02:01g was not found in people with Preta (Sub-Saharan African descent). A cluster including Branca (European) and Parda or non-informed (admixed) could be distinguished from both Preta (SubSaharan) and Indígena (Amerindian) groups, and from the Amarela (Asian) ones, which clustered with their original population. These results have implications on cross-population matching and can help in donor searches and population-based recruitment strategies.