Defining criteria for disease activity states in systemic juvenile idiopathic arthritis based on the systemic Juvenile Arthritis Disease Activity Score

Objective To develop and validate cutoff values in the systemic Juvenile Arthritis Disease Activity Score 10 (sJADAS10) that distinguish the states of inactive disease (ID), minimal disease activity (MiDA), moderate disease activity (MoDA), and high disease activity (HDA) in children with systemic juvenile idiopathic arthritis (sJIA), based on subjective disease state assessment by the treating pediatric rheumatologist. Methods The cutoffs definition cohort was composed of 400 patients enrolled at 30 pediatric rheumatology centers in 11 countries. Using the subjective physician rating as an external criterion, 6 methods were applied to identify the cutoffs: mapping, calculation of percentiles of cumulative score distribution, Youden index, 90% specificity, maximum agreement, and ROC curve analysis. Sixty percent of the patients were assigned to the definition cohort and 40% to the validation cohort. Cutoff validation was conducted by assessing discriminative ability. Results The sJADAS10 cutoffs that separated ID from MiDA, MiDA from MoDA, and MoDA from HDA were ≤ 2.9, ≤ 10, and > 20.6. The cutoffs discriminated strongly among different levels of pain, between patients with or without morning stiffness, and between patients whose parents judged their disease status as remission or persistent activity/flare or were satisfied or not satisfied with current illness outcome. Conclusion The sJADAS cutoffs revealed good metrologic properties in both definition and validation cohorts, and are therefore suitable for use in clinical trials and routine practice

Potential Symbiotic Effects of β-1,3 Glucan, and Fructooligosaccharides on the Growth Performance, Immune Response, Redox Status, and Resistance of Pacific White Shrimp, <i>Litopenaeus vannamei</i> to <i>Fusarium solani</i> Infection

The potential effects of dietary supplementation with β-1,3 glucan and fructooligosaccharides (β-1,3 GF) on antioxidant activities, immunological response, and growth performance of Pacific white shrimp (Litopenaeus vannamei) was investigated. Four diets (iso-energetic and iso-nitrogenous) with different levels of β-1,3 GF (0, 0.5, 1.0, and 1.5 g kg−1) were fed to healthy shrimp juveniles weighing 3 ± 0.5 g for 75 days. Shrimps were randomly distributed into 12 net enclosures at a density of 30 shrimp/net, and the experiment was performed in triplicate. The results revealed that long-term supplementation with 1.5 g kg−1 β-1,3 GF significantly improved shrimp weight gain, feed conversion ratio, and digestive enzyme profiles compared to the control diet group. However, there were no substantial variations in the contents of moisture, crude protein, total lipids, and ash in the muscles of shrimp fed on different diets. Surprisingly, all antioxidants (superoxide dismutase, catalase, glutathione peroxidase) and immune biomarkers (lysozyme, total hemocyte count, phenol oxidase, and respiratory burst) activities were significantly elevated with increasing levels of β-1,3 GF in the shrimp diet, and the highest values were recorded in the 1.5 g kg−1 diet groups. Challenge test results revealed that F. solani could cause a high mortality rate (86.7%) in a group fed a normal basal diet within 14 days at a dose of 5 × 104 conidia mL−1. Surprisingly, all dietary treated groups with different doses of β-1,3 GF showed high resistance against F. solani, represented by lower cumulative mortality rates (20–43.3%) compared to the control group. Moreover, most of the infected shrimp showed a typical black to brown gill lesion similar to that observed in the natural infection, where an identical fungus was successfully re-isolated from infected gills and muscles. Overall, this study recommends an appropriate incorporation level of β-1,3 GF that could enhance growth performance and improve the antioxidant activities, non-specific immunity, and disease resistance of L. vannamei, with an optimal level of 1.5 g kg−1

Developing transgenic wheat to encounter rusts and powdery mildew by overexpressing barley chi26 gene for fungal resistance

Abstract Background The main aim of this study was to improve fungal resistance in bread wheat via transgenesis. Transgenic wheat plants harboring barley chitinase (chi26) gene, driven by maize ubi promoter, were obtained using biolistic bombardment, whereas the herbicide resistance gene, bar, driven by the CaMV 35S promoter was used as a selectable marker. Results Molecular analysis confirmed the integration, copy number, and the level of expression of the chi26 gene in four independent transgenic events. Chitinase enzyme activity was detected using a standard enzymatic assay. The expression levels of chi26 gene in the different transgenic lines, compared to their respective controls, were determined using qRT-PCR. The transgene was silenced in some transgenic families across generations. Gene silencing in the present study seemed to be random and irreversible. The homozygous transgenic plants of T4, T5, T6, T8, and T9 generations were tested in the field for five growing seasons to evaluate their resistance against rusts and powdery mildew. The results indicated high chitinase activity at T0 and high transgene expression levels in few transgenic families. This resulted in high resistance against wheat rusts and powdery mildew under field conditions. It was indicated by proximate and chemical analyses that one of the transgenic families and the non-transgenic line were substantially equivalent. Conclusion Transgenic wheat with barley chi26 was found to be resistant even after five generations under artificial fungal infection conditions. One transgenic line was proved to be substantially equivalent as compared to the non-transgenic control

Listening to patients, for the patients: The COVAD Study-Vision, organizational structure, and challenges

Background: The pandemic presented unique challenges for individuals with autoimmune and rheumatic diseases (AIRDs) due to their underlying condition, the effects of immunosuppressive treatments, and increased vaccine hesitancy. Objectives: The COVID-19 vaccination in autoimmune diseases (COVAD) study, a series of ongoing, patient self-reported surveys were conceived with the vision of being a unique tool to gather patient perspectives on AIRDs. It involved a multinational, multicenter collaborative effort amidst a global lockdown. Methods: Leveraging social media as a research tool, COVAD collected data using validated patient-reported outcomes (PROs). The study, comprising a core team, steering committee, and global collaborators, facilitated data collection and analysis. A pilot-tested, validated survey, featuring questions regarding COVID-19 infection, vaccination and outcomes, patient demographics, and PROs was circulated to patients with AIRDs and healthy controls (HCs). Discussion: We present the challenges encountered during this international collaborative project, including coordination, data management, funding constraints, language barriers, and authorship concerns, while highlighting the measures taken to address them. Conclusion: Collaborative virtual models offer a dynamic new frontier in medical research and are vital to studying rare diseases. The COVAD study demonstrates the potential of online platforms for conducting large-scale, patient-focused research and underscores the importance of integrating patient perspective into clinical care. Care of patients is our central motivation, and it is essential to recognize their voices as equal stakeholders and valued partners in the study of the conditions that affect them