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The global banana industry is threatened by one of the most devastating diseases: Fusarium wilt of banana. Fusarium wilt of banana is caused by the soilborne fungus Fusarium oxysporum f. sp. cubense ( Foc), which almost annihilated the banana production in the late 1950s. A new strain of Foc, known as tropical race 4 (TR4), attacks a wide range of banana varieties, including Cavendish clones, which are the source of 99% of banana exports. In 2019, Foc TR4 was reported in Colombia, and more recently (2021) in Peru. In this study, we sequenced three fungal isolates identified as Foc TR4 from La Guajira (Colombia) and compared them against 19 whole-genome sequences of Foc TR4 publicly available, including four genome sequences recently released from Peru. To understand the genetic relatedness of the Colombian Foc TR4 isolates and those from Peru, we conducted a phylogenetic analysis based on a genome-wide set of single nucleotide polymorphisms (SNPs). Additionally, we compared the genomes of the 22 available Foc TR4 isolates, looking for the presence-absence of gene polymorphisms and genomic regions. Our results reveal that (i) the Colombian and Peruvian isolates are genetically distant, which could be better explained by independent incursions of the pathogen to the continent, and (ii) there is a high correspondence between the genetic relatedness and geographic origin of Foc TR4. The profile of present/absent genes and the distribution of missing genomic regions showed a high correspondence to the clades recovered in the phylogenetic analysis, supporting the results obtained by SNP-based phylogeny.

The main Theorem of this article provides a characterization of reductive homogeneous spaces equipped with some geometric structure (not necessarily pseudo-Riemannian) in terms of the existence of certain connection. This result generalizes the well-known Theorem of Ambrose and Singer for Riemannian homogeneous spaces (Ambrose and Singer in Duke Math J 25(4):647–669, 1958). We relax the conditions in this theorem and prove a characterization of reductive locally homogeneous manifolds. Finally, we apply these results to classify, with explicit expressions, reductive locally homogeneous almost symplectic, symplectic and Fedosov manifolds.

Background Currently we do not have an ideal biomarker in lupus nephritis (LN) that should help us to identify those patients with SLE at risk of developing LN or to determine those patients at risk of renal progression. We aimed to evaluate the development of a prognostic index for LN, through the evaluation of clinical, analytical and histological factors used in a cohort of lupus. We have proposed to determine which factors, 6 months after the diagnosis of LN, could help us to define which patients will have a worse evolution of the disease and may be, more aggressive treatment and closer follow-up. Methods A retrospective study to identify prognostic factors was carried out. We have included patients over 18 years of age with a clinical diagnosis of systemic lupus erythematosus (SLE) and kidney involvement confirmed by biopsy, who are followed up in our centre during the last 20 years. A multi-step statistical approach will be used in order to obtain a limited set of parameters, optimally selected and weighted, that show a satisfactory ability to discriminate between patients with different levels of prognosis. Results We analysed 92 patients with LN, although only 73 have been able to be classified according to whether or not they have presented poor renal evolution. The age of onset (44 vs. 32; p = 0.024), the value of serum creatinine (1.41 vs. 1.04; p = 0.041), greater frequency of thrombocytopenia (30 vs. 7%; p = 0.038), higher score in the renal chronicity index (2.47 vs. 1.04; p = 0.015), proliferative histological type (100%) and higher frequency of interstitial fibrosis (67 vs. 32%; p = 0.017) and tubular atrophy (67 vs. 32%; p = 0.018) was observed between two groups. The multivariate analysis allowed us to select the best predictive model for poor outcome at 6 months based on different adjustment and discrimination parameters. Conclusion We have developed a prognostic index of poor renal evolution in patients with LN that combines demographic, clinical, analytical and histopathological factors, easy to use in routine clinical practice and that could be an effective tool in the early detection and management.

El cultivo de tomate (Solanum lycopersicum), una de las hortalizas más cultivadas en el mundo, se enfrenta a diferentes patógenos del suelo que afectan su morfología, fisiología, bioquímica y regulación genética de las plantas. El hongo fitopatógeno Fusarium oxysporum f. sp. lycopersici (Fol) agente causal de la marchitez vascular del tomate causa pérdidas superiores al 60% en este cultivo. En esta revisión se presentan los mecanismos fisiológicos, bioquímicos y moleculares desarrollados en la interacción tomate – Fol. La co-evolución entre plantas y patógenos ha facilitado el desarrollo de mecanismos de defensa en las plantas que les permite protegerse frente a los efectos nocivos de la invasión por parte del patógeno, mientras que los patógenos implementan estrategias para imponerse frente a la resistencia de las plantas. Las consecuencias fisiológicas del ataque por Fol incluyen respuestas al déficit hídrico, regulaciones en la conductancia estomática, cambios en la fotosíntesis, así como alteraciones en los contenidos de clorofila y su fluorescencia. Estos cambios pueden ser explicados, en parte, con base en respuestas oxidativas, producción de metabolitos secundarios y activación de vías de señalización hormonales que hacen parte de una compleja red bioquímica activada tras la infección por el patógeno.

Tomato (Solanum lycopersicum L.) is a worldwide commercially important grown vegetable. Tomato plants are infected by different soil-borne pathogens that affect morphology, physiology, biochemistry and genetic regulation of plants. Fusarium oxysporum f. sp. lycopersici (Fol) is the causal agent of Fusarium wilt of tomato and causes significant yield losses-up to 60%- in tomato crops. This review presents the physiological, biochemical and molecular mechanisms undertaken in the tomato-Fol interaction. The co-evolution between plants and pathogens has allowed the development of an immune system to protect plants against the pathogen invasion, while pathogens implement strategies to overcome plant defense responses. Physiological consequences of F. oxysporum infection include responses to water deficit, regulation of stomatal conductance, influence on photosynthesis, chlorophyll fluorescence and chlorophyll content. These physiological and molecular changes can be, at least, partially explained by the activation of different processes, such as oxidative responses, secondary metabolites production and induction of hormone signal pathways, as part of a complex biochemical network activated during the infection.

A sensitive method was developed and validated for the determination of UV filters (oxybenzone, octocrylene, 4-methyl-benzylidene camphor, 2-ethylhexyl-4-methoxycinnamate and avobenzone) in tilapia muscle using matrix solid-phase dispersion followed by on-line solid-phase extraction–liquid chromatography/UV. The validation showed good linearity from 100 to 3600 ng g−1 with r2 values > 0.98. Precision values with relative standard deviations were

Despite its high toxicity, cyanide is used in several industrial processes, and as a result, large volumes of cyanide wastewater need to be treated prior to discharge. Enzymatic degradation of industrial cyanide wastewater by cyanide dihydratase, which is capable of converting cyanide to ammonia and formate, is an attractive alternative to conventional chemical methods of cyanide decontamination. However, the main impediment to the use of this enzyme for the biodegradation of cyanide is the intolerance to the alkaline pH at which cyanide waste is kept and its low thermoresistance. In the present study, the catalytic properties of whole E. coli cells overexpressing a cyanide dihydratase gene from B. pumilus were compared to those of the purified enzyme under conditions similar to those found in industrial cyanide wastewater. In addition, the capacity of whole cells to degrade free cyanide in contaminated wastewater resulting from the gold mining process was also determined. The characteristics of intracellular enzyme, relative to purified enzyme, included increased thermostability, as well as greater tolerance to heavy metals and to a lesser extent pH. On the other hand, significant enzymatic degradation (70%) of free cyanide in the industrial sample was achieved only after dilution. Nevertheless, the increased thermostability observed for intracellular CynD suggest that whole cells of E. coli overexpressing CynD are suited for process that operate at elevated temperatures, a limitation observed for the purified enzyme.

We report a draft genome assembly of the causal agent of tomato vascular wilt, Fusarium oxysporum f. sp. lycopersici isolate 59, obtained from the Andean region in Colombia.

The global banana industry is threatened by one of the most devastating diseases: Fusarium wilt (FWB). FWB is caused by the soil-borne fungus Fusarium oxysporum f. sp. cubense (Foc), which almost annihilated the banana production in the late 1950s. A new strain of Foc, known as tropical race 4 (TR4), attacks a wide range of banana varieties including Cavendish clones which are the source of 99% of banana exports. In 2019, Foc TR4 was reported in Colombia, and more recently (2021) in Peru. In this study, we sequenced three fungal isolates identified as Foc TR4 from La Guajira (Colombia) and compared them against 19 whole-genome sequences of Foc TR4 publicly available, including four genome sequences recently released from Peru. To understand the genetic relatedness of the Colombian Foc TR4 isolates and those from Peru, we conducted a phylogenetic analysis based on a genome-wide set of single nucleotide polymorphisms (SNPs). Additionally, we compared the genomes of the 22 available Foc TR4 isolates looking for the presence-absence of gene polymorphisms and genomic regions. Our results reveal that (i) the Colombian and Peruvian isolates are genetically distant, which could be better explained by independent incursions of the pathogen to the continent, and (ii) there is a high correspondence between the genetic relatedness and geographic origin of Foc TR4. The profile of present/absent genes and the distribution of missing genomic regions showed a high correspondence to the clades recovered in the phylogenetic analysis, supporting the results obtained by SNP-based phylogeny.

Background Cardiovascular disease and mental disorders frequently coexist. Selective serotonin reuptake inhibitors (SSRIs) are often used to treat depressive and anxiety disorders but have been associated with an increased risk of bleeding due to platelet dysfunction. Up to 10% of patients with coronary artery disease are concomitantly treated with dual antiplatelet therapy (DAPT) and SSRI. Previous studies have assessed the risk of bleeding in patients treated with SSRI and clopidogrel-based DAPT, with contradictory results. However, there is no data regarding the use of SSRI and potent P2Y12 inhibitors (ticagrelor, prasugrel) or triple antithrombotic therapy (TAT). Purpose To evaluate the bleeding outcomes in a real-world population of patients undergoing percutaneous coronary intervention (PCI) treated with SSRI and DAPT or TAT after a year follow-up. Methods We conducted a retrospective study including all patients undergoing PCI at a high-volume center during 2018. Patients taking SSRI were propensity-score-matched (PSM) 1:1 using nearest neighbor matching with patients not taking SSRI. The primary endpoint was major bleeding as defined by the International Society on Thrombosis and Haemostasis (ISTH) at 1 year. Kaplan-Meier and Cox regression were used to compare outcomes between treatment groups. Results Of 1063 patients that underwent PCI during the study period, 1002 met the inclusion criteria and 139 (13.9%) were receiving SSRI. Propensity score distributions, baseline characteristics and standardized mean differences (SMD) of the covariates used for PSM before and after adjustment are shown in Figure 1. In matched survival analysis, there was no significant difference in the primary endpoint at 1 year follow-up: mayor bleeding occurred in 2.9% of patients who received SSRI and in 2.9% of those with no SSRI (HR 1.01; CI 0.25 to 4.03; p=0.991) (Figure 2). Conclusion In routine clinical care, patients treated with SSRI and DAPT or TAT after PCI did not have a higher risk of bleeding after a year follow-up. Funding Acknowledgement Type of funding sources: None. Figure 1. Baseline characteristicsFigure 2. Survival curves by SSRI treatment

Background The impact of distance from residence to Tertiary Referral Hospital and cardiovascular (CV) outcomes in patients with coronary artery disease (CAD) is unknow. Despite longer travel distances hinder access to healthcare and may worsen CV outcomes, we hypothesize that Mediterranean lifestyle and behaviors in distant rural areas may be associated with a reduced risk of CV death and events. Purpose To investigate the association between travel distance to Tertiary Hospital and mid-term cardiovascular outcomes in a population of CAD patients in Southern Spain. Methods Retrospective study including all patients discharged after percutaneous coronary intervention (PCI) at a high-volume center in Southern Spain during 2018. Those belonging to another healthcare area were excluded. One-way driving distances from residence to hospital were computed using Google Maps Distance Matrix API with R package “gmapsdistance”. Patients were stratified into tertiles according to travel distance (short, STD; intermediate, ITD; and long, LTD). Kaplan-Meier (KM) and Multivariable Cox regression (adjusted for age, sex, atrial fibrillation, cancer history, prior revascularization and clinical presentation) were used to assess the impact of travel distance on CV death and a composite outcome of MACE (Myocardial Infarction, unplanned PCI and CV death). Results Of 1005 patients discharged after PCI during the study period, 966 met the selection criteria. Flowchart and baseline characteristics by distance groups are presented in Figure 1. Median travel distance tertiles were 6.1 (STD), 41.7 (ITD) and 78.4 (LTD). During a median follow-up of 31 (IQR 28–35) months, 50 cardiovascular deaths [STD 27 (8.4%), ITD 13 (4%), LTD 10 (3.1%), p=0.006)] and 63 MACE occurred [STD 45 (13.9%), ITD 37 (11.5%), LTD 26 (8.1%), p=0.060)]. KM curves for the three distance groups are shown in Figure 2. In univariable and multivariable Cox models, longer travel distances were associated with better outcomes, as for every 10 Km increase, there was a 11% and 7% decrease in the hazards of CV death (HR adj: 0.89, CI 0.82–0.98, p=0.029) and of MACE (HR adj: 0.93, CI 0.87–0.99, p=0.025), respectively. Conclusion Travel distance was inversely associated with CV events in a population of CAD patients in Southern Spain. Patients in the first tertile of distance had a higher rate of CV death. Multicenter studies involving other Mediterranean regions are needed to confirm these findings and to look for explanations. Funding Acknowledgement Type of funding sources: None. Flowchart and baseline characteristicsSurvival curves by distance groups

BackgroundSome factors associated with severe COVID-19 outcomes have been identified in patients with psoriasis (PsO) and inflammatory/autoimmune rheumatic diseases, namely older age, male sex, comorbidity burden, higher disease activity, and certain medications such as rituximab. However, information about specificities of patients with PsO, psoriatic arthritis (PsA) and axial spondyloarthritis (axSpA), including disease modifying anti-rheumatic drugs (DMARDs) specifically licensed for these conditions, such as IL-17 inhibitors (IL-17i), IL-23/IL-12 + 23 inhibitors (IL-23/IL-12 + 23i), and apremilast, is lacking.ObjectivesTo determine characteristics associated with severe COVID-19 outcomes in people with PsO, PsA and axSpA.MethodsThis study was a pooled analysis of data from two physician-reported registries: the Psoriasis Patient Registry for Outcomes, Therapy and Epidemiology of COVID-19 Infection (PsoProtect), comprising patients with PsO/PsA, and the COVID-19 Global Rheumatology Alliance (GRA) registry, comprising patients with PsA/axSpA. Data from the beginning of the pandemic up to 25 October, 2021 were included. An ordinal severity outcome was defined as: 1) not hospitalised, 2) hospitalised without death, and 3) death. A multivariable ordinal logistic regression model was constructed to assess the relationship between COVID-19 severity and demographic characteristics (age, sex, time period of infection), comorbidities (hypertension, other cardiovascular disease [CVD], chronic obstructive lung disease [COPD], asthma, other chronic lung disease, chronic kidney disease, cancer, smoking, obesity, diabetes mellitus [DM]), rheumatic/skin disease (PsO, PsA, axSpA), physician-reported disease activity, and medication exposure (methotrexate, leflunomide, sulfasalazine, TNFi, IL17i, IL-23/IL-12 + 23i, Janus kinase inhibitors (JAKi), apremilast, glucocorticoids [GC] and NSAIDs). Age-adjustment was performed employing four-knot restricted cubic splines. Country-adjustment was performed using random effects.ResultsA total of 5008 individuals with PsO (n=921), PsA (n=2263) and axSpA (n=1824) were included. Mean age was 50 years (SD 13.5) and 51.8% were male. Hospitalisation (without death) was observed in 14.6% of cases and 1.8% died. In the multivariable model, the following variables were associated with severe COVID-19 outcomes: older age (Figure 1), male sex (OR 1.53, 95%CI 1.29-1.82), CVD (hypertension alone: 1.26, 1.02-1.56; other CVD alone: 1.89, 1.22-2.94; vs no hypertension and no other CVD), COPD or asthma (1.75, 1.32-2.32), other lung disease (2.56, 1.66-3.97), chronic kidney disease (2.32, 1.50-3.59), obesity and DM (obesity alone: 1.36, 1.07-1.71; DM alone: 1.85, 1.39-2.47; obesity and DM: 1.89, 1.34-2.67; vs no obesity and no DM), higher disease activity and GC intake (remission/low disease activity and GC intake: 1.96, 1.36-2.82; moderate/severe disease activity and no GC intake: 1.35, 1.05-1.72; moderate/severe disease activity and GC intake 2.30, 1.41-3.74; vs remission/low disease activity and no GC intake). Conversely, the following variables were associated with less severe COVID-19 outcomes: time period after 15 June 2020 (16 June 2020-31 December 2020: 0.42, 0.34-0.51; 1 January 2021 onwards: 0.52, 0.41-0.67; vs time period until 15 June 2020), a diagnosis of PsO (without arthritis) (0.49, 0.37-0.65; vs PsA), and exposure to TNFi (0.58, 0.45-0.75; vs no DMARDs), IL17i (0.63, 0.45-0.88; vs no DMARDs), IL-23/IL-12 + 23i (0.68, 0.46-0.997; vs no DMARDs) and NSAIDs (0.77, 0.60-0.98; vs no NSAIDs).ConclusionMore severe COVID-19 outcomes in PsO, PsA and axSpA are largely driven by demographic factors (age, sex), comorbidities, and active disease. None of the DMARDs typically used in PsO, PsA and axSpA, were associated with severe COVID-19 outcomes, including IL-17i, IL-23/IL-12 + 23i, JAKi and apremilast.AcknowledgementsWe thank all the contributors to the COVID-19 PsoProtect, GRA and EULAR Registries.Disclosure of InterestsNone declared

BackgroundThere is a paucity of data in the literature about the outcome of patients with idiopathic inflammatory myopathy (IIM) who have been infected with SARS-CoV-2.ObjectivesTo investigate factors associated with severe COVID-19 outcomes in patients with IIM.MethodsData on demographics, number of comorbidities, region, COVID-19 time period, physician-reported disease activity, anti-rheumatic medication exposure at the clinical onset of COVID-19, and COVID-19 outcomes of IIM patients were obtained from the voluntary COVID-19 Global Rheumatology Alliance physician-reported registry of adults with rheumatic disease (from 17 March 2020 to 27 August 2021). An ordinal COVID-19 severity scale was used as primary outcome of interest, with each outcome category being mutually exclusive from the other:a) no hospitalization, b) hospitalization (and no death), or c) death. Odds ratios (OR) were estimated using multivariable ordinal logistic regression. In ordinal logistic regression, the effect size of a categorical predictor can be interpreted as the odds of being one level higher on the ordinal COVID-19 severity scale than the reference category.ResultsComplete hospitalization and death outcome data was available in 348 IIM cases. Mean age was 53 years, and 223 (64.1%) were female. Overall, 167/348 (48.0%) people were not hospitalized, 136/348 (39.1%) were hospitalized (and did not die), and 45/348 (12.9%) died. Older age (OR=1.59 per decade of life, 95%CI 1.32-1.93), male sex (OR=1.63, 95%CI 1.004-2.64; versus female), high disease activity (OR=4.05, 95%CI 1.29-12.76; versus remission), presence of two or more comorbidities (OR=2.39, 95%CI 1.22-4.68; versus none), prednisolone-equivalent dose >7.5 mg/day (OR=2.37, 95%CI 1.27-4.44; versus no glucocorticoid intake), and exposure to rituximab (OR=2.60, 95%CI 1.23-5.47; versus csDMARDs only) were associated with worse COVID-19 outcomes (Table 1).Table 1.Multivariable logistic regression analysis of factors associated with the ordinal COVID-19 severity outcomes. AZA, azathioprine; CI, confidence interval; combo, combination; CSA, ciclosporin; CYC, cyclophosphamide; DMARD, disease-modifying anti-rheumatic drug; b/tsDMARD, biologic/targeted synthetic DMARD, csDMARD, conventional synthetic DMARD; HCQ, hydroxychloroquine; IVIg, intravenous immunoglobulin; LEF, leflunomide; MMF, mycophenolate mofetil; mono, monotherapy; MTX, methotrexate; OR, odds ratio; Ref, reference; RTX, rituximab; SSZ, sulfasalazine; TAC, tacrolimus.VariableOR (95%CI)P-valueVariableOR (95%CI)P-valueAge (per decade)1.59 (1.32-1.93)ComorbiditiesMale sex1.63 (1.004-2.64)0.048NoneRefNAPrednisolone-equivalent doseOne1.46 (0.79-2.72)0.228NoneRefNATwo or more2.39 (1.22-4.68)0.011>0 to 7.5mg/day1.10 (0.57-2.11)0.779Physician-reported disease activity>7.5mg/day2.37 (1.27-4.44)0.007RemissionRefNAIVIg0.41 (0.15-1.16)0.093Low/moderate1.23 (0.67-2.28)0.504DMARDsHigh4.05 (1.29-12.76)0.018csDMARD only (mono or combi - HCQ, MTX, LEF, SSZ)RefNARegionNo DMARD1.84 (0.90-3.75)0.094EuropeRefNAb/tsDMARD mono or combi (except RTX)1.60 (0.49-5.26)0.435North America0.89 (0.49-1.61)0.694CSA/CYC/TAC mono or combi (except RTX or b/tsDMARDs)1.55 (0.52-4.58)0.429Other4.25 (2.21-8.16)AZA mono1.70 (0.69-4.19)0.249Time periodMMF mono1.22 (0.53-2.82)0.634Before 15 June 2020RefNAAZA/MMF combi (except RTX or b/tsDMARDs)0.71 (0.25-2.00)0.51716 June - 30 September 20200.58 (0.26-1.27)0.171RTX mono or combi2.60 (1.23-5.47)0.012After 1 October 20200.58 (0.35-0.95)0.032ConclusionThese are the first global registry data on the impact of COVID-19 on IIM patients. Older age, male gender, higher comorbidity burden, higher disease activity, higher glucocorticoid intake and rituximab exposure were associated with worse outcomes. These findings will inform risk stratification and management decisions for IIM patients.ReferencesNoneDisclosure of InterestsSu-Ann Yeoh: None declared, Milena Gianfrancesco: None declared, Saskia Lawson-Tovey: None declared, Kimme Hyrich Speakers bureau: AbbVie unrelated to this work, Grant/research support from: Pfizer, BMS, both unrelated to this work, Anja Strangfeld Speakers bureau: AbbVie, Celltrion, MSD, Janssen, Lilly, Roche, BMS, Pfizer, all unrelated to this work, Laure Gossec Consultant of: AbbVie, Amgen, BMS, Galapagos, Gilead, GSK, Janssen, Lilly, Novartis, Pfizer, Samsung Bioepis, Sanofi-Aventis, UCB, all unrelated to this work, Grant/research support from: Amgen, Galapagos, Lilly, Pfizer, Sandoz, all unrelated to this work, Loreto Carmona: None declared, Elsa Mateus Consultant of: Boehringer Ingelheim Portugal, not related to this work, Martin Schaefer: None declared, Christophe Richez Speakers bureau: Abbvie, Amgen, Astra Zeneca, Biogen, BMS, Celltrion, Eli Lilly, Galapagos, GSK, MSD, Novartis, and Pfizer, all unrelated to this abstract, Consultant of: Abbvie, Amgen, Astra Zeneca, Biogen, BMS, Celltrion, Eli Lilly, Galapagos, GSK, MSD, Novartis, and Pfizer, all unrelated to this abstract, Eric Hachulla Speakers bureau: Johnson & Johnson, GlaxoSmithKline, Roche-Chugai, all unrelated to this work, Consultant of: Bayer, Boehringer Ingelheim, GlaxoSmithKline, Johnson & Johnson, Roche-Chugai, Sanofi-Genzyme, all unrelated to this work, Grant/research support from: CSL Behring, GlaxoSmithKline, Johnson & Johnson, Roche-Chugai, Sanofi-Genzyme, all unrelated to this work, Marie Holmqvist: None declared, Carlo Alberto Scirè Grant/research support from: AbbVie, Lilly, both unrelated to this work, Rebecca Hasseli: None declared, Arundathi Jayatilleke: None declared, Tiffany Hsu: None declared, Kristin D’Silva: None declared, Victor Pimentel-Quiroz: None declared, Monica Vasquez del Mercado: None declared, Samuel Katsuyuki Shinjo: None declared, Edgard Reis Neto: None declared, Laurindo Rocha Jr: None declared, Ana Carolina de Oliveira e Silva Montandon Speakers bureau: GSK, not related to this work, Paula Jordan: None declared, Emily Sirotich: None declared, Jonathan Hausmann Speakers bureau: Novartis, Biogen, Pfizer, not related to this work, Consultant of: Novartis, Biogen, Pfizer, not related to this work, Jean Liew Grant/research support from: Pfizer research grant, completed in 2021, not related to this work, Lindsay Jacobsohn: None declared, Monique Gore-Massy Speakers bureau: Aurinia Pharmaceuticals, Boehringer Ingelheim, Bristol-Myers Squibb, not related to this work, Consultant of: Aurinia Pharmaceuticals, Boehringer Ingelheim, Bristol-Myers Squibb, not related to this work, Paul Sufka: None declared, Rebecca Grainger Speakers bureau: AbbVie, Janssen, Novartis, Pfizer and Cornerstones, all unrelated to this work, Consultant of: AbbVie, Novartis, both unrelated to this work, Suleman Bhana Shareholder of: Pfizer, Inc, Speakers bureau: AbbVie, Horizon, Novartis, and Pfizer, all unrelated to this work, Consultant of: AbbVie, Horizon, Novartis, and Pfizer, all unrelated to this work, Employee of: Pfizer, Inc, Zachary Wallace: None declared, Philip Robinson Speakers bureau: Abbvie, Janssen, Roche, GSK, Novartis, Lilly, UCB, all unrelated to this work, Paid instructor for: Lilly, unrelated to this work, Consultant of: GSK, Kukdong, Atom Biosciences, UCB, all unrelated to this work, Grant/research support from: Janssen, Pfizer, UCB and Novartis, all unrelated to this work, Jinoos Yazdany Consultant of: Aurinia, Astra Zeneca, Pfizer, all unrelated to this work, Grant/research support from: Astra Zeneca, Gilead, BMS Foundation, all unrelated to this work, Pedro Machado Speakers bureau: Abbvie, BMS, Celgene, Eli Lilly, Galapagos, Janssen, MSD, Novartis, Orphazyme, Pfizer, Roche and UCB, all unrelated to this work., Consultant of: Abbvie, BMS, Celgene, Eli Lilly, Galapagos, Janssen, MSD, Novartis, Orphazyme, Pfizer, Roche and UCB, all unrelated to this work.

Physiological processes of plants infected by vascular pathogens are mainly affected by vascular bundle obstruction, decreasing the absorption of water and nutrients and gas exchange by stomatal closure, and inducing oxidative cascades and PSII alterations. Chitosan, a derivative of chitin present in the cell wall of some organisms including fungi, induces plant defense responses, activating systemic resistance. In this study, three chitosan molecules (low, medium and high molecular weight) at different concentrations (0.5, 1, 1.5, 2, 2.5 and 3 mg mL-1) were assessed by in vitro tests against Fusarium oxysporum f. sp. lycopersici (Fol). Concentrations higher than 1 mg mL-1 were found to inhibit significantly the mycelial growth of Fol, with 95.8% of inhibition using chitosan with high molecular weight (3 mg mL-1). For in planta assays, chitosan treatment (low molecular weight 2.5 mg mL-1) showed significantly lower incidence and severity of wilting disease symptoms, 70 and 91%, respectively, compared to healthy plants used as a negative control. The effect of chitosan on the physiological and molecular responses of tomato plants infected with Fol was studied, evaluating the maximum potential quantum efficiency of PSII photochemistry (Fv/Fm), photochemical efficiency of PSII (Y(II)), stomatal conductance (gs), relative water content (RWC), proline content, photosynthetic pigments, dry mass, and differential gene expression (PAL, LOXA, ERF1, and PR1) of defense markers. A reduction of 70% in the incidence and 91% in the severity of the disease was achieved in plants treated with chitosan, mitigating the damage caused by Fol on Fv/Fm, Y(II), and chlorophyll contents by 23, 36, and 47%, respectively. Less impact was observed on gs, RWC, and dry mass (55, 11, and 26%, respectively). Chitosan-treated and Fol-infected plants over-expressed PR1a gene suggesting a priming-associated response. These results demonstrate the high potential of chitosan to protect tomato plants against Fol by regulating physiological and molecular responses in tomato plants.

[EN] Anthocyanins are a subclass of flavonoid pigments with important therapeutic properties beneficial to human health. Blood oranges are rich in these pigments, which present synergistic effects (i.e., anti-inflammatory and anti-obesity) with other orange juice phytonutrients. Anthocyanin biosynthesis is cold induced in blood citrus cultivars, requiring a broad day/night thermal range to get purple pigmentation in fruit. This cold-dependency limits geographically a reliable quality for commercial production to only a few regions worldwide. For example, cultivation of blood oranges under tropical/subtropical climates, as those of Brazil, yields fruit with very low level or lack of anthocyanins. A feasible alternative in tropical countries to enhance anthocyanin content is cold postharvest storage, as it has been shown that anthocyanin synthesis is induced when fruits are kept below 10°C for a few weeks after harvesting. Blood oranges kept at 9°C showed higher expression levels of anthocyanin biosynthetic genes, increased anthocyanin content and reached a darker purple coloration than those stored at 4°C. In order to gain insight on the effect of storage temperature on activation of anthocyanin biosynthesis and accumulation as well as on purple orange coloration, we have investigated the proteome of 'Moro' sweet orange [Citrus sinensis (L.) Osbeck] fruit stored either at 4°C (low temperature) or at 9°C (moderate temperature). Results on increased or reduced accumulation of specific proteins in the 'Moro' orange pulp upon storage at different temperatures reinforces that postharvest storage at 9°C could be better to enhance anthocyanin biosynthesis and accumulation on blood orange juices., This work was support by the Sao Paulo Research Foundation (FAPESP, Brazil) project (FAPESP 2014/12616-9) and Fundecitrus. LC was funded by grants from FAPESP (2014/23447-3).

Banana, the main export fruit for Colombia, is threatened by Fusarium wilt (FWB), caused by Fusarium oxysporum f. sp. cubense (Foc), tropical race 4 (TR4). Pathogen containment through disinfecting tools, machinery, shoes, and any means that may carry contaminated soil particles with proper disinfectants is at the forefront of disease management. In this study, the biocide efficacy of 10 commercial quaternary ammonium compounds (QACs) products and one based on glutaraldehyde (GA) were evaluated on both reproductive structures (microconidia and macroconidia) and survival spores (chlamydospores) of Foc TR4 (strain 140038) isolated from La Guajira, Colombia. QACs were evaluated at 1200 ppm and two exposure times: &lt, 1 and 15 min in the absence or presence of soil. For GA disinfectant, four different concentrations (500, 800, 1200, and 2000 ppm) were evaluated at both contact times in the presence of soil. In the absence of soil, all QACs showed 100% biocidal efficiency against microconidia, macroconidia, and chlamydospores at both &lt, 1 and 15 min. The presence of soil decreased the efficacy of disinfectants, but some of them, such as QAC3_1st, QAC7_4th, and QAC5_4th, showed 98%, 98%, and 100% efficacy against Foc TR4 chlamydospores, respectively, after &lt, 1 min of contact time. For instance, the GA-based disinfectant was able to eliminate all Foc TR4 propagules after 15 min for all concentrations tested.

BackgroundQualitative research is crucial to understand key stakeholders experiences and perspectives of care and health services. However, there is a lack of explicit frameworks and guidelines about how best to use qualitative evidence to formulate clinical recommendations. Part of the problem includes uncertainties about the contributions of qualitative research to the evidence, and the empirical and theoretical basis for appraising and synthesizing qualitative evidence in a standardized manner. In addition, most existing grading systems of qualitative research originates from quantitative research, and there is no clear guidance about how to incorporate qualitative research into the evidence hierarchy.ObjectivesTo conduct a systematic literature review (SLR) to answer two research questions (RQ):RQ1) What guidance (e.g., tools, checklists, frameworks) exists to assess the methodological quality of qualitative research employed to inform clinical recommendations?;RQ2) What methods exist specifically to grade levels of evidence for qualitative research?MethodsThe protocol for this review was registered on www.researchregistry.com (reviewregistry1240). Electronic databases (PubMed/Medline, EMBASE, Web of Science, COCHRANE, Emcare, PsycINFO, ERIC, Academic Search Premier, Sociological Abstracts, ProQuest Dissertations and Thesis Global) were searched for published and unpublished studies. Searches were completed from inception to 23rd October 2020. No restrictions were applied to clinical population. Eligible studies for both questions included primary articles and guideline documents available in English, describing the: i) development; ii) application of validated tools (e.g., checklists); iii) guidance on how to assess methodological quality of qualitive research and iv) guidance on how to grade levels of qualitative evidence. Opinion pieces and conference abstracts were excluded. Manual searches of the reference lists of full text articles were conducted. Two reviewers independently screened the titles, abstracts, and full text. A narrative synthesis was conducted to identify key aspects between the included studies.Results9071 records were retrieved (Figure 1). After de-duplication and title/abstract screening, 51 full-articles articles were assessed for eligibility yielding 15 included articles. For RQ1, six articles were included that described six tools (1) The society for Critical Care Medicine Family – Cantered Care Guidelines; 2) Nursing Management of the Second Stage of Labour evidence based clinical practice guidelines; 3) Jonna Briggs Institute Critical Appraisal of Qualitative Studies; 4) Critical Skill’s Appraisal Programme (CASP) and 6) the Modified CASP checklist). All tools ranged from 10 to 30 items, and evaluated research design, recruitment, ethical rigour, data collection and data analysis. Seven articles described one approach (GRADE CER-Qual) to assess methodological quality of qualitative research. This approach advised on the importance for assessing methodological limitations. For RQ2, two articles were included, one described a qualitative hierarchy of evidence, and another described a research pyramid that included a section on qualitative research.Figure 1.PRISMA diagram of included papersConclusionThis review highlights lack of consensus and limited availability of tools, checklists, and approaches to 1) appraise the methodological quality of qualitative research used to inform clinical recommendations and 2) grade levels of evidence for qualitative research. Current research agendas will need to determine the most relevant and appropriate method for the quality appraisal of qualitative research. This way, qualitative research could be more consistently and appropriately applied to the development of clinical recommendations.ReferencesN/ADisclosure of InterestsMandeep Sekhon: None declared, Annette de Thurah: None declared, George E. Fragoulis: None declared, Tanja Stamm: None declared, T.P.M. Vliet Vlieland: None declared, Bente Appel Esbensen: None declared, Heidi Lempp: None declared, Lindsay Bearne: None declared, Marios Kouloumas: None declared, Polina Pchelnikova: None declared, Thijs W. Swinnen: None declared, Chris Blunt: None declared, Ricardo J. O. Ferreira: None declared, Loreto Carmona: None declared, Elena Nikiphorou Speakers bureau: Celltrion, Pfizer, Sanofi, Gilead, Galapgos, AbbVie, Eli Lilly, Grant/research support from: Pfizer, Eli Lilly

BackgroundPatient research partners (PRPs) are increasingly included in research as well as guideline development task forces in rheumatology. In observational and registry studies the role and involvement of PRPs is not clear.ObjectivesWe aimed to evaluate current PRP involvement in registry research as well as benefits and barriers of implementation in practice.MethodsBased on a round table discussion during the EULAR Registries and observational drug studies meeting (RODS) in 2019 we used mixed methods methodology (survey and focus groups) to study the role of PRPs and involvement in research. The survey was sent to investigators of registries across Europe, participants of RODS meetings and members of the EULAR PARE (People with Arthritis / Rheumatism across Europe) network. Interested survey participants were further invited to one of three focus groups. The conduction of the focus groups (FG) was guided by a semi-structured guide based on the survey results. An inductive thematic analysis approach was applied to qualitative data.ResultsWe received 45 survey responses with around half of them from patients. The mean importance of PRP involvement was scored VAS±SD: 75±24mm (on a 100mm VAS), but the actual involvement was rather low (VAS: 32±20mm) and 12 participants had no experience with PRPs. The most common current practice was patient involvement in design of studies (32%), cooperation with patient organisation for recruitment (32%) and involvement of PRPs in the management board (32%). The most important need of PRP integration was attributed in the stages of design and preparation before recruitment. 11 survey participants even indicated that PRPs should be involved in all stages/tasks of research. During the focus groups 5 main themes (Table 1) could be identified. Complementary perspectives lead to greater synergy between researchers and patients and further the aim of deriving more valid outcomes. For successful involvement of PRPs, ideally PRPs should be heterogeneous in regard to their lived experience, education ought to be provided and researchers are responsible to offer an environment where PRPs feel comfortable. All FGs elaborated on different roles that PRPs can take on, although the researcher FGs outlined more different tasks of involvement than the PRP group. One theme summarised different barriers for PRP involvement, which have not been a topic of discussion in the FG composed of PRPs only.Table 1.Overview of themes, sub-themes, and presence of theme according to which focus group discussion.ThemeSub themeFocus GroupsResearcherResearcher and ProfessionalsPRPs1.Current experiences of PRPs involvement in researchResearcher experiences of involving PRPsXXPatient experiences of being involved as PRPsXX2.The role of PRP in registries and researchComplementary perspectives between researchers and PRPsXXXThe aim of patient involvement in researchX3.Points to consider for involving PRPs in researchConsider professional and social backgroundsXProvide PRPs education and trainingXXA welcoming environment for PRPs to contributeXX4.PRP involvement in different phases of the research processGive PRPs a voice in research committeesXXIdentify questions that are most relevant to patientsXXSelect the most relevant outcomes to patientsXXImprove recruitment strategiesXanalysis, interpretation and dissemination of resultsXX5.Barriers to involving PRPs in researchRecruiting PRPs from ethnic minoritiesXResearchers’ preconceptions of patients’ ability to be involved in researchXChallenging to ask patients to help analyse quantitative dataXLimited financial resourcesXFigure 1.the empirical research cycle - basis for discussion of the role, opportunities & challenges for patient research partners in registry and observational drug study research. X/Y indicates the number of votes for including PRPs at the respective stage.ConclusionThere is room and much appreciation of PRP involvement in registry research. Researchers and PRPs could use the strategies proposed in this study to define PRP roles and plans of ongoing and future studies.Disclosure of InterestsPaul Studenic: None declared, Mandeep Sekhon: None declared, Loreto Carmona: None declared, Maarten de Wit: None declared, Elena Nikiphorou Speakers bureau: Celltrion, Pfizer, Sanofi, Gilead, Galpagos, Abbvie, Eli Lilly, Grant/research support from: Pfizer, Eli Lilly

BackgroundThe number of new treatments available in rheumatology continues to increase. Kinase inhibitors, or jakinibs, pose an added challenge due to their variety and because they are oral. The most important role of the rheumatology nurse is patient education, especially on how to take the medication. The better the nurse understands the drugs, the better their practical recommendations and decisions will be and the better they will be able to respond to the patient. Guidelines or recommendations for inflammatory diseases do not usually include key practical details for nurses. It is our understanding that these points that will subsequently determine adherence and safety should be specially addressed in a specific document for nurses.ObjectivesTo establish practical, evidence-based nursing recommendations for the management of people with RA undergoing treatment with jakinibs.MethodsTo reach an evidence-based consensus we used systematic review and Delphi survey. A multidisciplinary panel of experts was formed with 6 rheumatology nurses, 2 rheumatologists, 1 psychologist, 1 dietician-nutritionist and 1 patient on treatment with jakinibs. This panel met on 2 occasions and was kept informed at all times of the progress of the project through the Miro platform. At the preparatory meeting the scope and users, structure and PICOt questions were established (these included efficacy and adverse effects, infections, cardiovascular risk, surgery, vaccination, pregnancy and breastfeeding, interactions and switches between jakinibs).The steering group made recommendations based on the issues raised at the first meeting. Only those that achieved 65% in favour were included as items in a Delphi survey. The Delphi survey was sent to all members of the society nurses and rheumatologists (n=60). Voting ranged from 0 to 10 (strongly disagree to strongly agree). Items with more than 75% agreement in the first round did not proceed to a second round.ResultsThe Table 1 shows the recommendations with their level of evidence and level of agreement after the Delphi (n=40; 67%). One item with only 50% agreement was rejected and did not proceed to a second round.Table 1.RecommendationLevel of evidenceDegree of agreementBefore starting treatment with a jakinib, it should be confirmed that the patient has no contraindications.5100%The patient’s efficacy and outcome expectations for the drug should be explored and those that need to be adjusted.585%It should be indicated that a double dose should not be taken if one is missed.4100%As with other DMARDs, the patient should be instructed that close management will follow.599%The use of contraception and discontinuation of the drug is recommended in case of gestational desire or unplanned pregnancy.396%It is recommended to explain the warning signs of infection: fever, blisters, burning pain in the ribs, itching when urinating, productive cough, diarrhoea, pus-filled wounds, phlegmon.1a100%It is recommended to instruct the patient on preventive measures for infectious diseases (dental and hand hygiene, HPV, social distance, etc.).1a89%Vaccination against common germs in immunocompromised persons and shingles with the current vaccine is recommended.1a93%CV risk factors should be monitored, and the patient trained for signs of thrombosis, HF or ischaemic heart disease.1a89%Close monitoring of elderly patients (CV risk, infections) is recommended.2100%Emphasis on adherence is recommended for jakinibs to be effective.3100%Before surgery, discontinuation of jakinib should be scheduled depending on the type of surgery and comorbidities.389%ConclusionThese recommendations will allow a practical approach to the management of jakinibs by nurses and enjoy an adequate consensus among potential users.Disclosure of InterestsJosé Maria Martín Martín Speakers bureau: Lilly, Consultant of: Lilly, Grant/research support from: Galapagos, Silvia García-Díaz Grant/research support from: Galapagos, Amparo Molina Grant/research support from: Galapagos, Carmen Dominguez Grant/research support from: Galapagos, Loreto Carmona: None declared, Laura Cano Garcia Grant/research support from: Galapagos

BackgroundThere is a lack of data on Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) vaccination safety in children and young people (CYP) with rheumatic and musculoskeletal diseases (RMDs). Current vaccination guidance is based on data from adults with RMDs or CYP without RMDs.ObjectivesTo describe the characteristics and outcomes of adolescents with inflammatory RMDs and adults with juvenile idiopathic arthritis (JIA) vaccinated against SARS-CoV-2.MethodsWe described patient characteristics, flares, and adverse events in adolescent cases under 18 with inflammatory RMDs and adult cases aged 18 or above with JIA submitted to the European Alliance of Associations for Rheumatology (EULAR) COVAX registry.ResultsThirty-six adolescent cases were reported from 4 countries, the most frequent diagnosis was JIA (42%). Over half (56%) reported early reactogenic-like adverse events (AEs) experienced within 7 days of vaccination. One mild polyarthralgia flare and one serious AE (malaise) were reported. No CYP reported SARS-CoV-2 infection post-vaccination.In addition to the adolescent cases, eleven countries reported 74 adult JIA cases. Among these, 62% reported early reactogenic-like AEs and two flares were reported (mild polyarthralgia and moderate uveitis). No serious AEs of special interest were reported among adults with JIA. Three 20-30 year old females were diagnosed with SARS-CoV-2 post-vaccination; all fully recovered.ConclusionIn this observational registry dataset, SARS-CoV-2 vaccines appeared safe in adolescents with RMDs and adults with JIA, with a low frequency of disease flares, serious AEs, and SARS-CoV-2 re-infection seen in both populations.Table 1.Characteristics of adolescents with RMDs and adults with JIA reported to the EULAR COVAX registryAdolescents with RMDs (N=36)Adults with JIA (N=74)SexFemale21 (58)54 (73)Male15 (42)20 (27)Age (median [IQR])15 [14.5, 17]26 [23, 31]Primary RMD diagnosisNon-systemic JIA10 (28)63 (85)Systemic JIA5 (14)11 (15)Systemic lupus erythematosus5 (14)Spondyloarthritis/psoriatic arthritis5 (14)Vasculitis/other RMD #11 (30)RMD disease activityRemission23 (64)33 (45)Minimal8 (22)21 (28)Moderate2 (6)12 (16)Severe1 (3)1 (1)Not applicable/missing2 (6)7 (10)RMD medicationNone9 (25)3 (4)b-DMARD9 (25)50 (68)cs-DMARD21 (58)25 (34)ts-DMARD5 (14)2 (3)Systemic glucocorticoids5 (14)1 (1)Colchicine7 (10)Other immunosuppressant *COVAX typePfizer/BioNTech33 (92)50 (68)Moderna2 (6)10 (14)AstraZeneca/Oxford1 (3)10 (14)Janssen1 (1)CoronaVac2 (3)UNK1 (1)COVAX doses111 (31)8 (11)22 (24)61 (82)31 (3)5 (7)RMD flareYes1 (3)2 (3)AEYes20 (56)46 (62)Early AEInjection site pain8 (22)16 (22)Redness6 (17)2 (3)Muscle pain1 (3)9 (12)Joint pain4 (11)3 (4)Headache9 (25)10 (14)Fever1 (3)26 (35)Chills2 (6)5 (7)Fatigue1 (3)13 (18)VomitingAE of special interestNon-serious1 (3)1 (1)Serious – important medical event1 (3)All data are N(%) of the column unless stated otherwise.# Other RMD includes Sjogren’s syndrome, systemic sclerosis, undifferentiated connective tissue disease, non-monogenic auto-inflammatory syndrome, chronic recurrent multifocal osteomyelitis, and other inflammatory arthritis* Other immunosuppressant includes ciclosporin, mycophenolate mofetil/mycophenolic acid.RMD, rheumatic and musculoskeletal disease; JIA, juvenile idiopathic arthritis; EULAR, European Alliance of Associations for Rheumatology; ANCA-associated vasculitis, anti-neutrophil cytoplasmic antibody-associated vasculitis; cs-, conventional synthetic; b-, biological; ts-, targeted synthetic; DMARD, disease-modifying anti-rheumatic drug; COVAX, Coronavirus vaccine; AE, adverse event.AcknowledgementsWe wish to thank all healthcare providers who entered data into the registry.Disclosure of InterestsSaskia Lawson-Tovey: None declared, Anja Strangfeld Speakers bureau: AbbVie, MSD, Roche, BMS, Pfizer, Elsa Mateus: None declared, Laure Gossec Consultant of: AbbVie, Amgen, BMS, Galapagos, Gilead, GSK, Janssen, Lilly, Novartis, Pfizer, Samsung Bioepis, Sanofi-Aventis, UCB, Grant/research support from: Amgen, Galapagos, Lilly, Pfizer, Sandoz, Loreto Carmona: None declared, Pedro Machado Speakers bureau: AbbVie, BMS, Celgene, Eli Lilly, Galapagos, Janssen, MSD, Novartis, Orphazyme, Pfizer, Roche, UCB, Consultant of: AbbVie, BMS, Celgene, Eli Lilly, Galapagos, Janssen, MSD, Novartis, Orphazyme, Pfizer, Roche, UCB, BERND RAFFEINER: None declared, Inita Bulina Speakers bureau: AbbVie, Pfizer, Janssen, Boehringer Ingelheim, Daniel Clemente Speakers bureau: Novartis, GSK, Julija Zepa Speakers bureau: AbbVie, Novartis, Janssen/Johnson & Johnson, Ana Maria Rodrigues Speakers bureau: Amgen, AbbVie, Grant/research support from: Amgen, Pfizer, AstraZeneca, Xavier Mariette Consultant of: BMS, Galapagos, Gilead, Janssen, Novartis, Pfizer, Sanofi-Aventis, UCB, Grant/research support from: Ose, Kimme Hyrich Speakers bureau: AbbVie, Grant/research support from: Pfizer, BMS, UCB

Physiological processes of plants infected by vascular pathogens are mainly affected by vascular bundle obstruction, decreasing the absorption of water and nutrients and gas exchange by stomatal closure, and inducing oxidative cascades and PSII alterations. Chitosan, a derivative of chitin present in the cell wall of some organisms including fungi, induces plant defense responses, activating systemic resistance. In this study, the effect of chitosan on the physiological and molecular responses of tomato plants infected with Fusarium oxysporum f. sp. lycopersici (Fol) was studied, evaluating the maximum potential quantum efficiency of PSII photochemistry (Fv/Fm), photochemical efficiency of PSII (Y(II)), photochemical quenching (qP), stomatal conductance (gs), relative water content (RWC), proline content, photosynthetic pigments, dry mass, and differential gene expression (PAL, LOXA, ERF1, and PR1) of defense markers. A reduction of 70% in the incidence and 91% in the severity of the disease was achieved in plants treated with chitosan, mitigating the damage caused by Fol on Fv/Fm, Y(II), and chlorophyll contents by 23%, 36%, and 47%, respectively. Less impact was observed on qP, gs, RWC, and dry mass (16%, 11%, and 26%, respectively). Chitosan-treated and Fol-infected plants over-expressed PR1a gene suggesting a priming-associated response. These results demonstrate the high potential of chitosan to protect tomato plants against Fol by regulating physiological and molecular responses in tomato plants.

In Colombia, tomato production under protected conditions represents an important economic contribution to the agricultural sector. Fusarium wilt diseases, caused by pathogenic formae speciales of the soil-borne fungus Fusarium oxysporum Schltdl., cause significant yield losses in tomatoes throughout the world. Investigation of the F. oxysporum&ndash, tomato pathosystem in Colombia is required to develop appropriate alternative disease management. In this study, 120 fungal isolates were obtained from four different departments in the Central Andean Region in Colombia from tomato crops with symptoms of wilt disease. A molecular characterization of the fungal isolates was performed using the SIX1, SIX3, and SIX4 effector genes of Fusarium oxysporum f. sp. lycopersici W.C. Snyder &amp, H.N. Hansen (Fol). Additionally, we developed a new specific marker to distinguish between Fusarium oxysporum f. sp. radicis-lycopersici Jarvis &amp, Shoemaker (Forl) and Fol isolates. Furthermore, a phylogenetic analysis using the Translation Elongation Factor 1-alpha (EF1a) gene was performed with the collected isolates. Two isolates (named Fol59 and Fol-UDC10) were identified as Fol race 2, four isolates were identified as Forl, six isolates were identified as F. solani, and most of the isolates were grouped within the F. oxysporum species complex. The phylogenetic tree of EF1a showed that most of the isolates could potentially correspond to nonpathogenic strains of F. oxysporum. Additional pathogenicity assays carried out with Fol59 and Fol-UDC10 confirmed that both isolates were highly virulent strains. This study represents a contribution to the understanding of the local interaction between tomatoes and F. oxysporum in Colombia.

In Colombia, tomato production under protected conditions represents an important economic contribution to the agricultural sector. Fusarium wilt diseases, caused by pathogenic formae speciales of the soil-borne fungus Fusarium oxysporum Schltdl., cause significant yield losses in tomatoes throughout the world. Investigation of the F. oxysporum–tomato pathosystem in Colombia is required to develop appropriate alternative disease management. In this study, 120 fungal isolates were obtained from four different departments in the Central Andean Region in Colombia from tomato crops with symptoms of wilt disease. A molecular characterization of the fungal isolates was performed using the SIX1, SIX3, and SIX4 effector genes of Fusarium oxysporum f. sp. lycopersici W.C. Snyder & H.N. Hansen (Fol). Additionally, we developed a new specific marker to distinguish between Fusarium oxysporum f. sp. radicis-lycopersici Jarvis & Shoemaker (Forl) and Fol isolates. Furthermore, a phylogenetic analysis using the Translation Elongation Factor 1-alpha (EF1a) gene was performed with the collected isolates. Two isolates (named Fol59 and Fol-UDC10) were identified as Fol race 2, four isolates were identified as Forl, six isolates were identified as F. solani, and most of the isolates were grouped within the F. oxysporum species complex. The phylogenetic tree of EF1a showed that most of the isolates could potentially correspond to nonpathogenic strains of F. oxysporum. Additional pathogenicity assays carried out with Fol59 and Fol-UDC10 confirmed that both isolates were highly virulent strains. This study represents a contribution to the understanding of the local interaction between tomatoes and F. oxysporum in Colombia.

Background:The consequences of the COVID-19 outbreak are unprecedented and have been felt by everyone around the world, including people with rheumatic and musculoskeletal diseases (RMDs). With the development of vaccines, the future is becoming brighter. Vaccines are a key pillar of public health and have been proven to prevent many serious diseases. However, vaccination also raises questions, especially for patients with inflammatory RMDs and/or treated with drugs that influence their immune system.Objectives:Our aim was to collect safety data among RMD patients receiving COVID-19 vaccines.Methods:The EULAR COVID-19 Vaccination (COVAX) Registry is an observational registry launched on 5 February 2021. Data are entered voluntarily by clinicians or associated healthcare staff; patients are eligible for inclusion if they have an RMD and have been vaccinated against SARS-CoV-2. Descriptive statistics are presented.Results:As of 27 April 2021, 1519 patients were reported to the registry. The majority were female (68%) and above the age of 60 (57%). Mean age was 63 years (SD 16), ranging from 15 to 97 years. A total of 28 countries contributed to the registry, with France (60%) and Italy (13%) as the highest contributors. The majority (91%) had inflammatory RMDs. Inflammatory joint diseases accounted for 51% of cases, connective tissue diseases 19%, vasculitis 16%, other immune mediated inflammatory diseases 4%, and non-inflammatory/mechanical RMDs 9%. The most frequent individual diagnoses were rheumatoid arthritis (30%), axial spondyloarthritis (8%), psoriatic arthritis (8%), systemic lupus erythematosus (SLE, 7%) and polymyalgia rheumatica (6%). At the time of vaccination, 45% were taking conventional synthetic DMARDs, 36% biological DMARDs, 31% systemic glucocorticoids, 6% other immunosuppressants (azathioprine; mycophenolate; cyclosporine; cyclophosphamide; tacrolimus), and 3% targeted synthetic DMARDs. The most frequent individual DMARDs were methotrexate (29%), TNF-inhibitors (18%), antimalarials (10%) and rituximab (6%). The vaccines administered were: 78% Pfizer, 16% AstraZeneca, 5% Moderna and 1% other/unknown; 66% of cases received two doses and 34% one dose. Mean time from 1st and 2nd dose to case report was 41 days (SD 26) and 26 days (SD 23), respectively. COVID-19 diagnosis after vaccination was reported in 1% (18/1519) of cases. Mean time from first vaccination until COVID-19 diagnosis was 24 days (SD 17). Disease flares were reported by 5% (73/1375) of patients with inflammatory RMDs, with 1.2% (17/1375) classified as severe flares. Mean time from closest vaccination date to inflammatory RMD flare was 5 days (SD 5). The most common flare types were arthritis (35/1375=2.5%), arthralgia (29/1375=2.1%), cutaneous flare (11/1375=0.8%) and increase in fatigue (11/1375=0.8%). Potential vaccine side effects were reported by 31% of patients (467/1519). The majority were typical early adverse events within 7 days of vaccination, namely pain at the site of injection (281/1519=19%), fatigue (171/1519=11%) and headache (103/1519=7%). Organ/system adverse events were reported by 2% (33/1519) but only 0.1% (2/1519) reported severe adverse events, namely a case of hemiparesis in a patient with systemic sclerosis/SLE overlap syndrome (ongoing at the time of reporting), and a case of giant cell arteritis in a patient with osteoarthritis (recovered/resolved without sequelae).Conclusion:The safety profiles for COVID-19 vaccines in RMD patients was reassuring. Most adverse events were the same as in the general population, they were non-serious and involved short term local and systemic symptoms. The overwhelming majority of patients tolerated their vaccination well with rare reports of inflammatory RMD flare (5%; 1.2% severe) and very rare reports of severe adverse events (0.1%). These initial findings should provide reassurance to rheumatologists and vaccine recipients, and promote confidence in COVID-19 vaccine safety in RMD patients, namely those with inflammatory RMDs and/or taking treatments that influence their immune system.Acknowledgements:EULAR COVID-19 Task Force; European Reference Network on rare and Complex Connective Tissue and Musculoskeletal Diseases; European Reference Network on Rare Immunodeficiency, Autoinflammatory and Autoimmune Diseases Network; all rheumatologists contributing to the EULAR COVAX Registry.Disclosure of Interests:Pedro M Machado Consultant of: Abbvie, BMS, Celgene, Eli Lilly, Janssen, MSD, Novartis, Orphazyme, Pfizer, Roche and UCB, all unrelated to this manuscript., Grant/research support from: Orphazyme, unrelated to this manuscript., Speakers bureau: Abbvie, BMS, Celgene, Eli Lilly, Janssen, MSD, Novartis, Orphazyme, Pfizer, Roche and UCB, all unrelated to this manuscript., Saskia Lawson-Tovey: None declared, Kimme Hyrich Grant/research support from: BMS, UCB, and Pfizer, all unrelated to this manuscript., Speakers bureau: Abbvie, Loreto Carmona Consultant of: her institute works by contract for laboratories among other institutions, such as Abbvie Spain, Eisai, Gebro Pharma, Merck Sharp & Dohme España, S.A., Novartis Farmaceutica, Pfizer, Roche Farma, Sanofi Aventis, Astellas Pharma, Actelion Pharmaceuticals España, Grünenthal GmbH, and UCB Pharma, all unrelated to this manuscript., Laure Gossec Grant/research support from: AbbVie, Amgen, BMS, Biogen, Celgene, Gilead, Janssen, Lilly, Novartis, Pfizer, Samsung Bioepis, Sanofi-Aventis, UCB, all unrelated to this manuscript., Speakers bureau: Amgen, Lilly, Janssen, Pfizer, Sandoz, Sanofi, Galapagos, all unrelated to this manuscript., Elsa Mateus Grant/research support from: LPCDR received support for specific activities: grants from Abbvie, Novartis, Janssen-Cilag, Lilly Portugal, Sanofi, Grünenthal S.A., MSD, Celgene, Medac, Pharmakern, GAfPA; grants and non-financial support from Pfizer; non-financial support from Grünenthal GmbH, outside the submitted work., Anja Strangfeld Speakers bureau: AbbVie, MSD, Roche, BMS, and Pfizer, all unrelated with this manuscript., BERND RAFFEINER: None declared, Tiphaine Goulenok: None declared, Olilvier Brocq: None declared, Martina Cornalba: None declared, José A Gómez-Puerta Speakers bureau: AbbVie, BMS, GSK, Janssen, Lilly, MSD, Roche and Sanofi., Eric Veillard: None declared, Ludovic Trefond: None declared, Jacques-Eric Gottenberg: None declared, Julien Henry: None declared, Patrick Durez: None declared, Gerd Rüdiger Burmester: None declared, Marta Mosca: None declared, Eric Hachulla: None declared, Hans Bijlsma: None declared, Iain McInnes: None declared, Xavier Mariette Consultant of: BMS, Galapagos, Gilead, Janssen, Novartis, Pfizer, Sanofi-Aventis, UCB, and grant from Ose, all unrelated to this manuscript.

Background:Cytopenia is a known side-effect of conventional synthetic disease modifying anti-rheumatic drugs (csDMARDs) in rheumatoid arthritis (RA). There is a lack of data on the comparative risk of cytopenia with different csDMARDs.Objectives:To assess the comparative risk of leukopenia and pancytopenia for the most frequently used first-line csDMARDs: methotrexate (MTX), hydroxychloroquine (HCQ), sulphasalazine (SSZ), and leflunomide (LEF).Methods:The study used data from 7 databases from 4 countries: CCAE, MDCR, Optum, IQVIA Ambulatory EMR (US); IQVIA THIN IMRD EMR (UK); IQVIA Disease Analyzer EMR (Germany); and SIDIAP (Spain). Cohorts included adult patients with a diagnosis of RA from 2005 to 2019 with at least one-year prior follow-up, no prior inflammatory arthritis, initiaton of first-line csDMARD, and no cytopenia in the preceding 30 days. Participants were followed from one day after treatment initiation to the earliest of event occurrence, treatment discontinuation/switching plus 14 days in the on-treatment analysis, five years in the intent-to-treat (ITT) analysis, or loss to follow-up. MTX was used as reference group. Cox models were fitted with propensity score stratification for observed confounding and negative control outcomes calibration for residual error. Estimates across database were pooled where I2Results:Overall 166,347 patients were included. Pooled rates of leukopenia and pancytopenia for MTX were 10.9 and 3.2 per 1,000 person years, respectively. Figure 1 and 2 show the results for the different databases and pooled estimates where applicable. Database estimates are not reported where adequate covariate balance not attained, and meta-analysis not shown where I2>0.4. MTX showed slightly higher hazards of leukopenia and of pancytopenia compared to LEF but no consistently differential risks compared to HCQ or SSZ.Figure 1.Calibrated hazard ratios (95% CI) vs MTX, on-treatment analysisConclusion:Cytopaenia is rare, and apparently more frequent with MTX and less with LEF. Since prior full blood counts were inconsistently obtained in fewer than 50% of csDMARD new users (e.g. more frequent in MTX [42%] than HCQ [32%] in CCAE and Optum; roughly equal in MDCR), these results should inform future monitoring recommendations.Figure 2.Calibrated hazard ratios (95% CI) vs MTX, ITT analysisDisclosure of Interests:Loreto Carmona Grant/research support from: Novartis Farmaceutica, SA, Pfizer, S.L.U., Merck Sharp & Dohme España, S.A., Roche Farma, S.A, Sanofi Aventis, AbbVie Spain, S.L.U., and Laboratorios Gebro Pharma, SA (All trhough institution), James Weaver Shareholder of: J&J Shares, Grant/research support from: Full-time employment salary from Janssen, Consultant of: Janssen employee, Employee of: Janssen, Paid instructor for: Janssen employee, have instructed at conferences, Speakers bureau: Janssen employee, have spoken at conferences, Edward Burn: None declared, Ben Illingens: None declared, David Vizcaya Employee of: Bayer, Ruta Sawant Shareholder of: AbbVie, Employee of: AbbVie, Talita Duarte-Salles: None declared, Patrick Ryan: None declared, Daniel Prieto-Alhambra Grant/research support from: Professor Prieto-Alhambra has received research Grants from AMGEN, UCB Biopharma and Les Laboratoires Servier, Consultant of: DPA’s department has received fees for consultancy services from UCB Biopharma, Speakers bureau: DPA’s department has received fees for speaker and advisory board membership services from Amgen

Cyanide is toxic to most living organisms. The toxicity of cyanide derives from its ability to inhibit the enzyme cytochrome C oxidase of the electronic transport chain. Despite its high toxicity, several industrial processes rely on the use of cyanide, and considerable amounts of industrial waste must be adequately treated before discharge. Biological treatments for the decontamination of cyanide waste include the use of microorganisms and enzymes. Regarding the use of enzymes, cyanide dihydratase (CynD), which catalyzes the conversion of cyanide into ammonia and formate, is an attractive candidate. Nevertheless, the main impediment to the effective use of this enzyme for the biodegradation of cyanide is the marked intolerance to the alkaline pH at which cyanide waste is kept. In this work, we explore the operational capabilities of whole E. coli cells overexpressing Bacillus pumilus CynD immobilized in three organic polymer matrices: chitosan, polyacrylamide, and agar. Remarkably, the immobilized cells on agar and polyacrylamide retained more than 80% activity even at pH 10 and displayed high reusability. Conversely, the cells immobilized on chitosan were not active. Finally, the suitability of the active complexes for the degradation of free cyanide from a solution derived from the gold processing industry was demonstrated.