Immunomodulatory therapies for the treatment of SARS-CoV-2 infection: an update of the systematic literature review to inform EULAR points to consider

OBJECTIVE: To update the EULAR 2020 systematic literature review (SLR) on efficacy and safety of immunomodulatory agents in SARS-CoV-2 infection. METHODS: As part of a EULAR taskforce, a systematic literature search update was conducted from 11 December 2020 to 14 July 2021. Two reviewers independently identified eligible studies and extracted data on efficacy and safety of immunomodulatory agents used therapeutically in SARS-CoV-2 infection at any stage of disease. The risk of bias (RoB) was assessed with validated tools. RESULTS: Of the 26 959 records, 520 articles were eligible for inclusion. Studies were mainly at high or unclear RoB. New randomised controlled trials (RCTs) on tocilizumab clarified its benefit in patients with severe and critical COVID-19, mainly if associated with glucocorticoids. There are emergent data on the usefulness of baricitinib and tofacitinib in severe COVID-19. Other therapeutic strategies such as the use of convalescent plasma and anti-SARS-CoV-2 monoclonal antibodies showed efficacy in subjects not mounting normal anti-SARS-CoV-2 antibody responses. CONCLUSION: This new SLR confirms that some immunomodulators (tocilizumab and JAK inhibitors) have a role for treating severe and critical COVID-19. Although better evidence is available compared with the previous SLR, the need of RCT with combination therapy (glucocorticoids+anti-cytokines) versus monotherapy with glucocorticoids still remains alongside the need for standardisation of inclusion criteria and outcomes to ultimately improve the care and prognosis of affected people. This SLR informed the 2021 update of the EULAR points to consider on the use of immunomodulatory therapies in COVID-19

Efflux Activity Differentially Modulates the Levels of Isoniazid and Rifampicin Resistance among Multidrug Resistant and Monoresistant Mycobacterium tuberculosis Strains

With the growing body of knowledge on the contribution of efflux activity to Mycobacterium tuberculosis drug resistance, increased attention has been given to the use of efflux inhibitors as adjuvants of tuberculosis therapy. Here, we investigated how efflux activity modulates the levels of efflux between monoresistant and multi- and extensively drug resistant (M/XDR) M. tuberculosis clinical isolates. The strains were characterized by antibiotic susceptibility testing in the presence/absence of efflux inhibitors, molecular typing, and genetic analysis of drug-resistance-associated genes. Efflux activity was quantified by real-time fluorometry. The results demonstrated that all the M. tuberculosis clinical strains, susceptible or resistant, presented a faster, rapid, and non-specific efflux-mediated short-term response to drugs. The synergism assays demonstrated that the efflux inhibitors were more effective in reducing the resistance levels in the M/XDR strains than in the monoresistant strains. This indicated that M/XDR strains presented a more prolonged response to drugs mediated by efflux compared to the monoresistant strains, but both maintain it as a long-term stress response. This work shows that efflux activity modulates the levels of drug resistance between monoresistant and M/XDR M. tuberculosis clinical strains, allowing the bacteria to survive in the presence of noxious compounds.publishersversionpublishe

Bats and hawkmoths form mixed modules with flowering plants in a nocturnal interaction network

Based on the conceptual framework of pollination syndromes, pollination networks should be composed of well-delimited subgroups formed by plants that diverge in floral phenotypes and are visited by taxonomically different pollinators. Nevertheless, floral traits are not always accurate in predicting floral visitors. For instance, flowers adapted to bat-pollination are larger and wider, enabling the exploitation by other nocturnal animals, such as hawkmoths. Thus, should an interaction network comprising bats and hawkmoths, the most important nocturnal pollinators in the tropics, be formed of mixed-taxon modules due to cross-syndrome interactions? Here, we analyzed such a network to test whether resource plants are shared between the two taxa, and how modules differ in terms of species morphologies. We sampled interactions through pollen grains collected from floral visitors in a Caatinga dry forest in northeastern Brazil. The network was modular yet interwoven by cross-syndrome interactions. Hawkmoths showed no restriction to visit the wider chiropterophilous flowers. Furthermore, bats represented a subset of a hawkmoth-dominated network, as they were restricted to chiropterophilous flowers due to constraints in accessing narrower sphingophilous flowers. As such, the bat-dominated module encompassed relatively wider flowers, but hawkmoths, especially long-tongued ones, were unrestricted by floral width or length. Thus, pollination of flowers with open architectures must be investigated with caution, as they are accessible to a wide array of floral visitors, which may result in mixed-pollination systems. Future research should continue to integrate different syndromes and pollinator groups in order to reach a better understanding of how pollination-related functions emerge from community-level interactions. Abstract in Portuguese is available with online material.Fil: Queiroz, Joel A.. Universidade Estadual da Paraiba; BrasilFil: Diniz, Ugo M.. Universidade do Brasília; BrasilFil: Vazquez, Diego P.. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto Argentino de Investigaciones de las Zonas Áridas. Provincia de Mendoza. Instituto Argentino de Investigaciones de las Zonas Áridas. Universidad Nacional de Cuyo. Instituto Argentino de Investigaciones de las Zonas Áridas; Argentina. Universidad Nacional de Cuyo. Facultad de Ciencias Exactas y Naturales; ArgentinaFil: Quirino, Zelma M.. Universidade Estadual da Paraiba; BrasilFil: Santos, Francisco A. R.. Universidade Estadual de Feira de Santana; BrasilFil: Mello, Marco A. R.. Universidade de Sao Paulo; BrasilFil: Machado, Isabel. Universidade Federal de Pernambuco; Brasi

Germinación De Semillas De Asclepias Subulata En Condiciones De Casa Sombra Utilizando Ácido Giberélico

The objective of this work was to evaluate the use of gibberellic acid (GA3) in the seed germination of Asclepias subulata Decne., plant of the wild flora of the Sonoran Desert of interest for reforestation, industry and medicinal use. Since there is no information about their domestication, it is of fundamental importance to carry out germination tests to ensure their propagation, given the low germination percentage that this species presents. Seeds of A. subulata were collected in the Sonoran Desert, within the area known as Cerro del Bachoco. Six concentrations of gibberellic acid (GA3) (0, 125, 250, 500, 1000 and 2000 ppm) were tested at two soak times (24 and 48 hours) and one control without any treatment. Germination power, germination time at 25, 50 and 75%, and the germination rate index were evaluated. Germination was considered when the seed emits the hypocotyl outside the substrate used. Chemical scarification with GA3 has a positive influence on seed germination of A. subulata. The highest percentage of germination was obtained with GA3 in concentrations of 250 to 2000 ppm, at 24 and 48 hours of soaking. Germination time was affected by the concentration of GA3, being favored at a concentration of 1000 and 2000 ppm at 24 and 48 hours of soaking; while in other treatments 75% of germination was not reached. Chemical scarification with GA3 favored the germination rate index

Stress and coping in sport

O estresse é entendido como um desequilíbrio substancial entre uma demanda e a capacidade de resposta, sob condições em que a falha em satisfazer a exigência tem consequências significativas. No esporte, esse assunto tem sido alvo de estudos a mais de quarenta anos, con- tudo, ainda há muito o que se entender sobre esse complexo tema. Assim, o objetivo dessa pesquisa foi realizar uma revisão sistemática de literatura sobre o estresse e coping no esporte, identificando as principais teorias, suas evoluções ao longo dos anos e as formas efi- cientes de investigação. Para a análise, consultamos as bases de da- dos: Google® acadêmico, Science Direct e Scielo, buscando por livros, teses, dissertações e artigos relacionados ao tema. Como resultados, destacamos o estudo de Balbinotti et al. (2013) que propôs uma nova classificação de coping, e o Modelo Transacional Cognitivo, Motivacio- nal e Relacional (Lazarus, 1991; Lazarus & Folkman, 1984), que verifica o processo de adaptação dos atletas ao contexto esportivo. Fletcher e Fletcher (2005) e Gomes (2014) também contribuíram para o desen- volvimento do Modelo de Lazarus, considerando as emoções presen- tes ao fim do processo cognitivo.Stress is seen as a substantal imbalance between demand and responsiveness, under conditons where failure to meet the requirement has signifcant consequences. In sports, this issue has been investgated over forty years, however, there is stll much to understand about this complex topic. This research aimed to conduct a systematc review of literature on stress and coping in sport, identfying the main theories, their evoluton over the years and the efcient forms of research. For the analysis, we consulted the databases: Academic Google®, Science Direct and Scielo, searching for books, theses, dissertatons and papers related to the topic. As result, we highlight the study Balbinot et al. (2013) who proposed a new classifcaton of coping, and the Transactonal Stress Model (Lazarus, 1991, Lazarus & Folkman, 1984), which verifes the process of adaptaton of athletes to the sportng context. Fletcher and Fletcher (2005) and Gomes (2014) also contributed to the development of Lazarus Model in an emoton perspectve.info:eu-repo/semantics/publishedVersio

Physical activity interventions in schools for improving lifestyle in European countries

Background : In the last decades, children’s and adolescents’ obesity and overweight have increased in European Countries. Unhealthy eating habits and sedentary lifestyle have been recognized to determine such an epidemic. Schools represent an ideal setting to modify harmful behaviors, and physical activity could be regarded as a potential way to avoid the metabolic risks related to obesity. Methods : A systematic review of the literature was carried out to summarize the evidence of school-based interventions aimed to promote, enhance and implement physical activity in European schools. Only randomized controlled trials were included, carried out in Europe from January 2000 to April 2014, universally delivered and targeting pupils aged between 3 and 18 years old. Results : Forty-seven studies were retrieved based either on multicomponent interventions or solely physical activity programs. Most aimed to prevent obesity and cardiovascular risks among youths. While few studies showed a decrease in BMI, positive results were achieved on other outcomes, such as metabolic parameters and physical fitness. Conclusion : Physical activity in schools should be regarded as a simple, non-expensive and enjoyable way to reach all the children and adolescents with adequate doses of moderate to vigorous physical activity

Optimization of Au:CuO thin films by plasma surface modification for high-resolution LSPR gas sensing at room temperature

In this study, thin films composed of gold nanoparticles embedded in a copper oxide matrix (Au:CuO), manifesting Localized Surface Plasmon Resonance (LSPR) behavior, were produced by reactive DC magnetron sputtering and post-deposition in-air annealing. The effect of low-power Ar plasma etching on the surface properties of the plasmonic thin films was studied, envisaging its optimization as gas sensors. Thus, this work pretends to attain the maximum sensing response of the thin film system and to demonstrate its potential as a gas sensor. The results show that as Ar plasma treatment time increases, the host CuO matrix is etched while Au nanoparticles are uncovered, which leads to an enhancement of the sensitivity until a certain limit. Above such a time limit for plasma treatment, the CuO bonds are broken, and oxygen is removed from the film’s surface, resulting in a decrease in the gas sensing capabilities. Hence, the importance of the host matrix for the design of the LSPR sensor is also demonstrated. CuO not only provides stability and protection to the Au NPs but also promotes interactions between the thin film’s surface and the tested gases, thereby improving the nanocomposite film’s sensitivity. The optimized sensor sensitivity was estimated at 849 nm/RIU, which demonstrates that the Au-CuO thin films have the potential to be used as an LSPR platform for gas sensors.This research was sponsored by the Portuguese Foundation for Science and Technology (FCT) in the framework of the Strategic Funding UIDB/04650/2020 and by the project CO2Plasmon with reference EXPL/CTM-REF/0750/2021. M.P. acknowledges her Ph.D. Scholarship from FCT, with reference SFRH/BD/137076/2018. Diana I. Meira acknowledges her Ph.D. Scholarship from FCT, with reference SFRH/BD/143262/2019

Immunomodulatory therapies for the treatment of SARS-CoV-2 infection: an update of the systematic literature review to inform EULAR points to consider

Objective To update the EULAR 2020 systematic literature review (SLR) on efficacy and safety of immunomodulatory agents in SARS-CoV-2 infection. Methods As part of a EULAR taskforce, a systematic literature search update was conducted from 11 December 2020 to 14 July 2021. Two reviewers independently identified eligible studies and extracted data on efficacy and safety of immunomodulatory agents used therapeutically in SARS-CoV-2 infection at any stage of disease. The risk of bias (RoB) was assessed with validated tools. Results Of the 26 959 records, 520 articles were eligible for inclusion. Studies were mainly at high or unclear RoB. New randomised controlled trials (RCTs) on tocilizumab clarified its benefit in patients with severe and critical COVID-19, mainly if associated with glucocorticoids. There are emergent data on the usefulness of baricitinib and tofacitinib in severe COVID-19. Other therapeutic strategies such as the use of convalescent plasma and anti-SARS-CoV-2 monoclonal antibodies showed efficacy in subjects not mounting normal anti-SARS-CoV-2 antibody responses. Conclusion This new SLR confirms that some immunomodulators (tocilizumab and JAK inhibitors) have a role for treating severe and critical COVID-19. Although better evidence is available compared with the previous SLR, the need of RCT with combination therapy (glucocorticoids+anti-cytokines) versus monotherapy with glucocorticoids still remains alongside the need for standardisation of inclusion criteria and outcomes to ultimately improve the care and prognosis of affected people. This SLR informed the 2021 update of the EULAR points to consider on the use of immunomodulatory therapies in COVID-19

Pathophysiology of acute respiratory syndrome coronavirus 2 infection: a systematic literature review to inform EULAR points to consider

Background The SARS-CoV-2 pandemic is a global health problem. Beside the specific pathogenic effect of SARS-CoV-2, incompletely understood deleterious and aberrant host immune responses play critical roles in severe disease. Our objective was to summarise the available information on the pathophysiology of COVID-19. Methods Two reviewers independently identified eligible studies according to the following PICO framework: P (population): patients with SARS-CoV-2 infection; I (intervention): any intervention/no intervention; C (comparator): any comparator; O (outcome) any clinical or serological outcome including but not limited to immune cell phenotype and function and serum cytokine concentration. Results Of the 55 496 records yielded, 84 articles were eligible for inclusion according to question-specific research criteria. Proinflammatory cytokine expression, including interleukin-6 (IL-6), was increased, especially in severe COVID-19, although not as high as other states with severe systemic inflammation. The myeloid and lymphoid compartments were differentially affected by SARS-CoV-2 infection depending on disease phenotype. Failure to maintain high interferon (IFN) levels was characteristic of severe forms of COVID-19 and could be related to loss-of-function mutations in the IFN pathway and/or the presence of anti-IFN antibodies. Antibody response to SARS-CoV-2 infection showed a high variability across individuals and disease spectrum. Multiparametric algorithms showed variable diagnostic performances in predicting survival, hospitalisation, disease progression or severity, and mortality. Conclusions SARS-CoV-2 infection affects both humoral and cellular immunity depending on both disease severity and individual parameters. This systematic literature review informed the EULAR ‘points to consider’ on COVID-19 pathophysiology and immunomodulatory therapies