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Background & Aim: With larger accessibility and increased number of patients being treated with CART cell therapy, real-world toxicity continues to remain a significant challenge to its widespread adoption. We have previously shown that allogeneic umbilical cord blood derived (UCB) regulatory T cells (Tregs) can resolve uncontrolled inflammation and can treat acute and immune mediated lung injury in a xenogenic model as well as in patients suffering from COVID-19 acute respiratory distress syndrome. The unique properties of UCB Tregs including: i) lack of plasticity when exposed to inflammatory micro-environments;ii) no requirement for HLA matching;iii) long shelf life of cryopreserved Tregs;and iv) immediate product availability for on demand treatment, makes them an attractive source for treating acute inflammatory syndromes. Therefore, we hypothesized that add-on therapy with UCB derived Tregs may resolve uncontrolled inflammation responsible for CART cell therapy associated toxicity. Methods, Results & Conclusion(s): UCB Tregs were added in 1:1 ratio to CART cells, where no interference in their ability to kill CD19+ Raji cells, was detected at different ratios : 8:1 (80.4% vs. 81.5%);4:1 (62.0% vs. 66.2%);2:1 (50.1% vs. 54.7%);1:1 (35.4% vs. 44.1%) (Fig 1A). In a xenogenic B cell lymphoma model, multiple injections of Tregs were administered after CART injection (Fig 1B), which did not impact distribution of CD8+ T effector cells (Fig 1C) or CART cells cells (Fig 1D) in different organs. No decline in the CAR T levels was observed in the Tregs recipients (Fig 1E). Specifically, no difference in tumor burden was detected between the two arms (Fig 2A). No tumor was detected in CART+Tregs in liver (Fig 2B) or bone marrow (Fig 2C). A corresponding decrease in multiple inflammatory cytokines in peripheral blood was observed in CART+Tregs when compared to CART alone (Fig 2D). Here we show "proof of concept" for add-on therapy with Tregs to mitigate hyper-inflammatory state induced by CART cells without interference in their on-target anti-tumor activity. The timing of Tregs administration after CART cells have had sufficient time for forming synapse with tumor cells allows for preservation of their anti-tumor cytotoxicity, such that the infused Tregs home to the areas of tissue damage to bind to the resident antigen presenting cells which in turn collaborate with Tregs to resolve inflammation. Such differential distribution of cells allow for a Treg "cooling blanket" and lays ground for clinical study. [Figure presented]Copyright © 2023 International Society for Cell & Gene Therapy
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Objectives: To evaluate the safety and immunogenicity of CoronaVac and ChAdOx1 vaccines against SARS-CoV-2 in patients with Rheumatoid Arthritis (RA). Method(s): These data are from the 'SAFER (Safety and Efficacy on COVID-19 Vaccine in Rheumatic Diseases)' study, a Brazilian multicentric longitudinal phase IV study to evaluate COVID-19 vaccine in immunomediated rheumatic diseases (IMRDs). Adverse events (AEs) in patients with RA were assessed after two doses of ChAdOx1 or CoronaVac. Stratification of postvaccination AEs was performed using a diary, filled out daily. The titers of neutralizing antibodies against the receptor-biding domain of SARS-CoV-2 (anti-RBD) were measured by chemilumine scence test after each dose of immunizers. Proportions between groups were compared using the Chi-square and Fisher's exact tests for categorical variables. Clinical Disease Activity Index (CDAI) before and after vaccination was assessed using the McNemar test. Result(s): A total of 188 patients with RA were included in the study, most of them were female. CoronaVac was used in 109 patients and ChAdOx1 in 79. Only mild AEs were observed. The more common AEs after the first dose were pain at injection site (46,7%), headache (39,4%), arthralgia (39,4%) and myalgia (30,5%), and ChAdOx1 had a higher frequency of pain at the injection site (66% vs 32 %, p alpha 0.001) arthralgia (62% vs 22%, p alpha 0.001) and myalgia (45% vs 20%, p alpha 0.001) compared to CoronaVac. The more common AEs after the second dose were pain at the injection site (37%), arthralgia (31%), myalgia (23%) and headache (21%). Arthralgia (41,42 % vs 25 %, p = 0.02) and pain at injection site (51,43% vs 27%, p = 0.001) were more common with ChAdOx1. No patients had a flare after vaccination. The titers of anti-RBDafter two doses of ChAdOx1 were higher compared to two doses of CoronaVac (6,03 BAU/mL vs 4,67 BAU/mL, p alpha 0,001). Conclusion(s): The frequency of local adverse effects, particularly pain at injection site, was high. AEs were more frequent with ChAdOx1, especially after the first dose. The use of the immunizers dis not change the degree of inflammatory activity of the disease. In patients with RA, ChAdOx1 was more immunogenic than CoronaVac. .
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For the past few years, tourism has been interpreted by official narratives of public policies in Brazil, as a possible route for socioeconomic development and for social inclusion. Thus, many experiments took place in the world for this purpose and, among them, the community based tourism or CBT, which in theory, seeks the development of tourist locations, based on central premises for the conservation of natural resources, valuing culture and local protagonism. Under this inspiration, this article aims to analyze the way in which the conceptual premises related to CBT has been expressed in the narratives of public tourism policies, in the Brazilian case, seeking to contribute to the construction of a baseline to guide a qualified debate on the topic, in a post-pandemic scenario of Covid-19.Therefore, the methodology adopted was based on bibliographic and documentary research, considering public tourism policies in the period between 2003 and 2018 as the universe of analysis. The analysis suggests that, despite some of the theoretical premises that guide CBT being expressed in the most recent documents, in general, this has been interpreted, predominantly, by the logic of the market in the narratives of public policies, in contradiction with the theoretical basis, which has guided the debate on the theme. Thus, considering this trend in a scenario of post-pandemic uncertainties in Covid-19, the risk of instrumentalising this practice in official narratives seems to be evident, in order to meet the interests of the market, through the false discourse of fighting social inequalities.
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A new Dual-Dagum-G (DDa-G) family is defined as a good competitor to the Beta-G and Kumaraswamy-G generators, which are widely applied in several areas. Some of its mathematical properties are addressed. We obtain the maximum likelihood estimates, and some simulations prove the consistency of the estimates. The flexibility of this family is shown through a COVID-19 data set. We propose a new regression based on a special distribution of the DDa-G family, and provide a sensitivity analysis by using data from 1,951 COVID-19 patients collected in Curitiba, Brazil. © 2022 - IOS Press. All rights reserved.
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Background: Patients with autoimmune infammatory diseases (AID) have been prioritized for urgent vaccination to mitigate COVID-19 risk. However, few studies in the literature assessed the immunogenicity and safety of the COVID-19 vaccine in patients with AID. Objectives: In this context, the present study aims to evaluate the immunogenic-ity and safety of the vaccine against COVID-19 in patients with AID. Methods: These data are from 'Safety and efficacy on COVID-19 Vaccine in Rheumatic Disease'-SAFER study, a Brazilian multicentric prospective phase IV study to evaluate COVID-19 Vaccine in AID, in the real-life, in Brazil. Immunogenicity and adverse events (AE) from a single center were assessed, after 2 doses of ChAdOx1 (Oxford/AstraZeneca), 8 weeks of interval, in patients with AID and healthy controls (HC). Inclusion criteria were age ≥ 18 years and fulflling criteria according to international classifcation for AID. Exclusion criteria: pregnancy, previous severe AE to any vaccine, other immunosuppression causes. Stratifcation of post-vaccination AE was performed using a diary, flled out daily and returned at the end of 28 days for each dose. Participants were followed up through blood collection for measurement of IgG antibodies against SARS-CoV-2 spike receptor-binding domain by chemiluminescence (SARS-CoV-2 IgG II Quant assay, Abbott Laboratories, Abbott Park, IL, USA) at baseline and 28 days after the second dose. The seropositivity was defned for titers ≥50 AU/mL. Quantitative analyses were presented as observed frequency, percentage, central tendency, and variability measurements. The sample's normal distribution was verifed through the Shapiro-Wilk test. The Kruskal-Wallis test and the post-hoc Dwass-Steel-Critchlow-Fligner pairwise comparisons test were used to compare the IgG-S titers between the groups through the evaluation period. Categorical data were addressed using the Fisheŕs exact or Chi-squared (χ2) test. An alpha level of 5% signifcance was used in all analyses. Results: A total of 377 volunteers with AID and 50 HC were included in the study. Patients with spondyloarthritis (N=64), systemic lupus erythematosus (N=63), rheumatoid arthritis (N=61), primary Sjögren's syndrome (N=61), vasculitis (N=31), systemic sclerosis (N=14), inflammatory myopathy (N=9), Crohńs disease (N=49), ulcerative colitis (N=11) and other systemics AID (N=12) were evaluated. Both groups had female predominance (73.5% vs. 74.0%, p=0.937) and were homogeneous for age (43.5 vs. 41.7,p=0.308). The seroconversion among those not reactive (IgG-S negative at baseline) (46 HC and 191 AID), 28 days after second dose was 97.1% for spondyloar-thritis (p=0.425), systemic lupus erythematosus 88.2% (0.006), rheumatoid arthritis 93.5% (0.158), primary Sjögren's syndrome 92.6% (0.133), systemic sclerosis or inflammatory myopathy 47.1% (0.001), inflammatory bowel disease 100% (0.999) and vasculitis 80% (0.006), while in healthy control was 100%. In comparison with HC, there was a statistically significant difference in IgG-S titles only in systemic sclerosis or inflammatory myopathy (1.694 AU/ml vs. 3.719 AU/ml;p=0.006). Both groups only presented mild AE. Pain at the injection (85.7% vs. 78.4%, p=0.239), headache (67.3% vs. 53.8, p=0.074) and fatigue (59.2% Vs. 46.2%, p=0.089) were more common in HC than AID. Overall, reactions like arthralgia (52.6 vs. 22.4%, p<0.001), hematoma (14.1 vs. 4.1%, p=0.05), cutaneous rash (9.5 vs. 0%, p=0.024) were more frequent in AID. Most participants related that they felt safer after receiving a COVID-19 vaccination, and 52.4% did not reported a worse patient global assessment (PGA) index. Conclusion: In conclusion, our data indicated that ChAdOx1 vaccine is safe and induced high titers and seroconversion rate in AID. More severe AID, such as vasculitis, systemic lupus erythematosous, and systemic sclerosis and myositis showed a lower seroconversion rate. Further analysis will explore the association between immunossupressant and reactivity, and booster dose.
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Tourism represents a complex contemporary phenomenon that involves economic, social, environmental, ethical, political and symbolical dimensions and, for its interpretation, a multidimensional and interdisciplinary approach is essential, mediated by a critical political perspective. Nevertheless, tourism public policies are predominantly developed through a market or an economic bias, dissociated from other sectorial policies which tend to mask some essential issues in tourism planning. Based on these assumptions, this article aims to investigate, preliminarily, the global trends in terms of public policies aimed at the conservation of biodiversity, in its articulation with tourism, with emphasis on protected areas. The qualitative research was carried on based on bibliographic and documental analysis, considering the timeframe between 1992 - agreement by the Convention on Biological Diversity (CBD) - and 2019, year before the official Covid 19 Pandemic announcement. Evident efforts, at the global level, are recognized from the CBD, agreement, to articulate conservation of biodiversity and tourism public policies. However, this movement is still incipient in view of the growing risks to biodiversity and the urgency for tourism development on a sustainable basis, in the Post Covid 19 Pandemics context.
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There is a noticeable lag between Brazilian Teams and Robocup Division A teams in Small Size Soccer League (SSL). One of the main reasons is the difference in the mechanical project and how effective the dribbler and kicker systems conduct and kick the ball to other robots or the goal. This paper describes the process to develop both dribbler and kicker systems to an SSL robot, beginning with a review of Robocup Division A teams and the main Brazilian teams' projects. A 3D modeling of the dribbler and kicker systems is presented considering innovation effectiveness and space. The systems and models were evaluated via finite element simulation tests. The manufacturing process and its challenges are not in the scope of this paper due to Covid-19 limitations to lab access and will be part of future works. All parts designed are available for public use, allowing other teams to use them, modified or not, on their projects. © 2020 IEEE.
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Objective: To analyze risk factors for death in individuals with Severe Acute Respiratory Syndrome by COVID-19. Methods: Retrospective cohort, with adult individuals with COVID-19, between March and September 2020, notified by Epidemiological Surveillance System in state of Acre, Brazil. Cox Regression was used. Results: Of the 57,700 individuals, the incidence was 2,765.4/100,000 inhabitants and mortality 61.8/100,000 inhabitants. The risk factors for death were: male gender (HR=1.48 - 95%CI 1.25;1.76), age >= 60 years old (HR=10.64 - 95%CI 8.84;12.81), dyspnea (HR=4.20 - 95%CI 3.44;5.12), multimorbidity (HR=2.23 - 95%CI 1.77;2.81), with emphasis heart problems and diabetes. The symptoms sore throat (HR=0.44 - 95%CI 0.27;0.71) and headache (HR=0.44 - 95%CI 0.22;0.89) were present in mild cases of the disease. Conclusion: Men, older adults, those with heart disease, diabetes and dyspnea were at risk of death in the occurrence by COVID-19.