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ID PMID Title PublicationDate abstract
34218237 Seroprevalence of babesiosis in immunocompetent and immunocompromised individuals. 2021 Jun 16 Interest in Babesia species is gaining an increasing attention as an emerging tick-borne pathogen. Infection is primarily transmitted through Ixodes ticks, and alternatively by blood transfusions from asymptomatic donors. AIM: The aim of the study was detection of Babesia seroprevalence in different groups of population with the usage of experimental B. divergens whole-cell slide antigen and commercial B. microti immunofluorescence assay substrate slide. MATERIALS AND METHODS: Indirect immunofluorescence assay trial was performed by testing of 145 blood samples of different origins: healthy individuals (60 - blood donors), risk groups (30 - HIV-infected individuals, 30 - Lyme disease patients) and false-positive IFA controls (10 - seropositive rheumatoid arthritis patients, 15 - patients with toxoplasmosis). RESULTS: The study revealed Babesia antibodies to B. divergens (6.9%) and B. microti (3.4%) that were detected with higher (p <0.05) frequency in HIV-infected individuals (26.7%) and in Lyme disease patients (16.7%) than at blood donors (1.7%). Diagnostically significant IgG titres were detected at 23.3% HIV-infected individuals, 13.3% Lyme disease patients and by 1.7% of blood donors and patients with seropositive latent toxoplasmosis. Specific IgM were detected at 20.0% HIV-infected individuals and 13.3% Lyme disease patients. 57.1% of diagnostically significant titres in HIV-infected and Lyme disease patients were represented by IgG and IgM. CONCLUSIONS: Immunofluorescence assay has a limited use in babesiosis: in acute form with negative microscopy or PCR; in chronic, asymptomatic and subclinical form with low level of parasitemia; and in retrospective and epidemiological studies of the population immune structure. Clinicians need to have increased awareness of babesiosis, and further studies are needed to clarify the optimal management of this infection in risk groups (including HIV-infected patients and blood donors).
34125296 Epidemiology of glucocorticoid-induced osteoporosis and management of associated fracture 2021 Nov INTRODUCTION: Glucocorticoid-induced osteoporosis (GIOP) is associated with a high fracture risk. Practice guidelines by the Japanese Society for Bone and Mineral Research in 2014 recommend bone densitometry and appropriate treatment to reduce this risk. The study objectives were to describe characteristics of GIOP patients in Japan and to evaluate their management in a subgroup of patients without comorbid cancer. MATERIALS AND METHODS: This retrospective cohort study was performed using the Medical Data Vision (MDV) database from Japan. Adult patients initiating oral glucocorticoid treatment with a total GIOP risk score ≥ 3, based on the 2014 practice guideline, identified between 2009 and 2019 were eligible. A subgroup of patients without any cancer diagnosis was also identified. Data were extracted on demographics, concurrent medical conditions, use of bone densitometry, and osteoporosis treatment. RESULTS: 25,569 patients were eligible, of whom 12,227 had a confirmed cancer diagnosis. Mean age was 68.5 years and 12,356 patients (48.3%) were women. Concurrent medical conditions of interest were documented in 14,887 patients, most frequently rheumatoid arthritis (n = 4185) and asthma (n = 3085). Yearly bone densitometry was performed in 6.5% (n = 865) of the cancer-free subgroup; 51.8% (n = 6905) were prescribed an osteoporosis treatment, most frequently bisphosphonates (n = 5132; 74.3%). Between 2011 and 2018, rates of densitometry were stable, whereas prescription rates increased from 40.0 to 51.8%. CONCLUSION: In spite of publication of guidelines for GIOP management, there is an important treatment gap in their application in everyday practice. For this reason, public health measures to increase physician awareness of GIOP are needed.
34046493 The Living with Pulmonary Fibrosis questionnaire in progressive fibrosing interstitial lun 2021 Apr The Living with Idiopathic Pulmonary Fibrosis (L-IPF) questionnaire was developed with substantial input from patients with idiopathic pulmonary fibrosis (IPF) to assess symptoms and health-related quality of life (HRQoL). Because IPF is the prototypical chronic fibrosing interstitial lung disease (ILD) with a progressive phenotype, we expanded applicability of the L-IPF by deleting the word "idiopathic", creating the L-PF (Living with Pulmonary Fibrosis) questionnaire, and then assessed its relevance among patients with progressive fibrosing ILDs in one-to-one interviews. Patients in the USA and Germany with any progressive fibrosing ILD other than IPF were asked about their disease and symptoms, completed the 44-item L-PF questionnaire (comprising two modules that assess symptoms and impacts of disease) and then answered a series of debriefing questions. Interviews were recorded, transcribed and coded for qualitative content analysis. 20 patients were interviewed, but time constraints meant not all were asked about all items. The most frequent diagnoses were rheumatoid arthritis-associated ILD (25%) and mixed connective tissue disease-associated ILD (20%). Almost all patients endorsed the symptoms assessed by the L-PF: shortness of breath (19 out of 20 patients), cough (19 out of 20) and fatigue (18 out of 20). Most patients endorsed impacts of progressive fibrosing ILD on activities of daily living, physical well-being, sleep, emotional well-being, and social aspects of their lives. Most patients had an overall positive impression of the Symptoms module and understood items as intended. All seven patients asked understood the items of the Impacts module. The L-PF contains concepts relevant and important to patients with progressive fibrosing ILD, and items are understood as intended.
33987340 Prevalence and clinical characteristics of antibiotics associated drug induced liver injur 2021 Apr BACKGROUND: The use of antibiotics increases recently. Accordingly, the incidence of antibiotics associated with drug induced liver injury (DILI) also increases. The purpose of this study is to evaluate the proportion and the clinical characteristics of antibiotic associated with DILI. METHODS: This study is a retrospective study of analyzed adult patients who were referred to the department of hepatology for the elevation of liver function tests and the frequency of elevated liver enzyme of patients with prescribed antibiotics during the same period at outpatient setting as a validation set. RESULTS: Antibiotics associated with DILI (64.0%) are the most common reason agent among consulting to hepatology department. Rheumatoid arthritis related drugs (11.0%), health supplements (5.0%), herbal medicines (4.0%), anti-viral drugs, anti-inflammatory analgesics/acetaminophen and lipid-lowering agents (3.0%) were next common causative drug for DILI in inpatients setting (training set). The frequency of antibiotics associated with DILI was high in order of flomoxef, cetrazole, ceftriaxone, vancomycin, piperacillin/tazobactam and amoxicillin/clavulanate. In the same period, 32% of the patients who prescribed flomoxef showed elevated liver enzyme levels above the upper normal limit. The prevalence of flomoxef induced DILI (>3 folds of ALT) was 13% and liver enzyme levels were five times higher than upper normal limits in 5% of flomoxef groups. Hypertension or diabetes was the risk factor of flomoxef associated with DILI. CONCLUSIONS: The Prevalence of antibiotics associated with DILI was 2-14%. Co-morbidity with diabetes and hypertension was the risk factor of flomoxef associated with DILI.
33971967 DHODH and cancer: promising prospects to be explored. 2021 May 10 Human dihydroorotate dehydrogenase (DHODH) is a flavin-dependent mitochondrial enzyme catalyzing the fourth step in the de novo pyrimidine synthesis pathway. It is originally a target for the treatment of the non-neoplastic diseases involving in rheumatoid arthritis and multiple sclerosis, and is re-emerging as a validated therapeutic target for cancer therapy. In this review, we mainly unravel the biological function of DHODH in tumor progression, including its crucial role in de novo pyrimidine synthesis and mitochondrial respiratory chain in cancer cells. Moreover, various DHODH inhibitors developing in the past decades are also been displayed, and the specific mechanism between DHODH and its additional effects are illustrated. Collectively, we detailly discuss the association between DHODH and tumors in recent years here, and believe it will provide significant evidences and potential strategies for utilizing DHODH as a potential target in preclinical and clinical cancer therapies.
33832827 Safety of treatment with chloroquine and hydroxychloroquine: A ten-year systematic review 2021 Jun OBJECTIVE: To estimate the incidence rate ratio (IRR) of adverse events (AE) in chloroquine or hydroxychloroquine users. METHODS: We systematically reviewed randomized controlled trials (RCTs), using MEDLINE (2010-2020) and EMBASE (2010-2020) databases, reporting AE in chloroquine or hydroxychloroquine users during treatment for lupus, rheumatoid arthritis, malaria and COVID-19. The protocol for this systematic review is registered at the PROSPERO database (CRD42020197938). The quality of the included studies was assessed using the Cochrane risk-of-Bias tool and relevant data were extracted though a customized data collection form, independently, by two authors. The IRR of AE was estimated using a random-effect model meta-analysis and heterogeneity was evaluated by T(2) and I(2). Subgroup analysis was performed, and publication bias was assessed by funnel-plot. RESULTS: Forty-six RCTs met our eligibility criteria and were included in our analysis (23132 patients). There was not a single death attributed to chloroquine or hydroxychloroquine use in the included RCTs. The IRR of general AE during antimalarial use was 1.15 [CI 95% 1.01-1.31]. COVID-19 patients treated with either antimalarial presented an 83% and 165% higher risk of developing general and gastrointestinal AE, respectively, in comparison with controls. The use of antimalarial increased the risk of developing dermatological AE by 92% in malarial studies and reduced by 65% in lupus studies. We did not find a significatively higher risk of cardiovascular nor ophthalmological AE in antimalarial users. CONCLUSIONS: Our data reinforces that chloroquine and hydroxychloroquine have a good safety profile though caution is advised when using higher than usual doses in hospitalized COVID-19 patients.
33752694 Entomotherapy: a study of medicinal insects of seven ethnic groups in Nagaland, North-East 2021 Mar 22 BACKGROUND: The ethnic communities in Nagaland have kept a close relationship with nature since time immemorial and have traditionally used different kinds of insects and their products as folk medicine to treat a variety of human ills and diseases. The present study was conducted to record the entomotherapeutic practices of seven different ethnic groups of Nagaland. METHOD: Documentation is based on semi-structured questionnaires and group discussions with a total of 370 informants. The data collected were analysed using fidelity level (FL) and informant consensus factor (ICF). RESULTS: Fifty species of medicinal insects belonging to 28 families and 11 orders were identified in connection with treatments of at least 50 human ailments, of which the most frequently cited were coughs, gastritis, rheumatoid arthritis, stomach ache and wound healing. Mylabris sp. showed the highest fidelity level (FL) of 100% for its therapeutic property as a dermatologic agent, while the informant consensus factor (ICF) ranged from 0.66 to 1.00. The use of medicinal insects varies amongst the seven ethnic groups, suggesting that differences in cultures and geographic location can lead to the selection of specific insect species for specific medicinal purposes. The largest number of insect species appear to be used for treating gastrointestinal, dermatological and respiratory diseases. CONCLUSION: The list of medicinal insect species, many of which are reported for the first time in the present study, suggests the presence of a considerable diversity of therapeutically important insect species in the region and elaborate folk medicinal knowledge of the local ethnic groups. This knowledge of insects not just as a food, but also as therapy is passed down verbally from generation to generation, but is in danger of being lost if not documented in a systematic way. Having stood the test of time, traditional folk medicinal knowledge and its contribution through entomotherapy should not be regarded as useless as it has the potential to lead to the development of novel drugs and treatment methods.
33693483 MixTwice: large-scale hypothesis testing for peptide arrays by variance mixing. 2021 Mar 8 Peptide microarrays have emerged as a powerful technology in immunoproteomics as they provide a tool to measure the abundance of different antibodies in patient serum samples. The high dimensionality and small sample size of many experiments challenge conventional statistical approaches, including those aiming to control the false discovery rate (FDR). Motivated by limitations in reproducibility and power of current methods, we advance an empirical Bayesian tool that computes local false discovery rate statistics and local false sign rate statistics when provided with data on estimated effects and estimated standard errors from all the measured peptides. As the name suggests, the MixTwice tool involves the estimation of two mixing distributions, one on underlying effects and one on underlying variance parameters. Constrained optimization techniques provide for model fitting of mixing distributions under weak shape constraints (unimodality of the effect distribution). Numerical experiments show that MixTwice can accurately estimate generative parameters and powerfully identify non-null peptides. In a peptide array study of rheumatoid arthritis (RA), MixTwice recovers meaningful peptide markers in one case where the signal is weak, and has strong reproducibility properties in one case where the signal is strong. Availability MixTwice is available as an R software package https://cran.rproject. org/web/packages/MixTwice/ Supplementary information Supplementary data are available at Bioinformatics online.
33542692 Koumine Suppresses IL-1β Secretion and Attenuates Inflammation Associated With Blocking R 2020 Koumine (KM), one of the primary constituents of Gelsemium elegans, has been used for the treatment of inflammatory diseases such as rheumatoid arthritis, but whether KM impacts the activation of the NOD-like receptor protein 3 (NLRP3) inflammasome remains unknown. This study aimed to explore the inhibitory effect of KM on NLRP3 inflammasome activation and the underlying mechanisms both in vitro using macrophages stimulated with LPS plus ATP, nigericin or monosodium urate (MSU) crystals and in vivo using an MSU-induced peritonitis model. We found that KM dose-dependently inhibited IL-1β secretion in macrophages after NLRP3 inflammasome activators stimulation. Furthermore, KM treatment efficiently attenuated the infiltration of neutrophils and suppressed IL-1β production in mice with MSU-induced peritonitis. These results indicated that KM inhibited NLRP3 inflammasome activation, and consistent with this finding, KM effectively inhibited caspase-1 activation, mature IL-1β secretion, NLRP3 formation and pro-IL-1β expression in LPS-primed macrophages treated with ATP, nigericin or MSU. The mechanistic study showed that, KM exerted a potent inhibitory effect on the NLRP3 priming step, which decreased the phosphorylation of IκBα and p65, the nuclear localization of p65, and the secretion of TNF-α and IL-6. Moreover, the assembly of NLRP3 was also interrupted by KM. KM blocked apoptosis-associated speck-like protein containing a CARD (ASC) speck formation and its oligomerization and hampered the NLRP3-ASC interaction. This suppression was attributed to the ability of KM to inhibit the production of reactive oxygen species (ROS). In support of this finding, the inhibitory effect of KM on ROS production was completely counteracted by H(2)O(2), an ROS promoter. Our results provide the first indication that KM exerts an inhibitory effect on NLRP3 inflammasome activation associated with blocking the ROS/NF-κB/NLRP3 signal axis. KM might have potential clinical application in the treatment of NLRP3 inflammasome-related diseases.
33542649 The Clinical Value of the RA-Adjusted Fracture Risk Assessment Tool in the Fracture Risk P 2021 OBJECTIVE: This study aimed to explore the clinical value of the fracture risk assessment tool (FRAX) in the fracture risk prediction of Chinese patients after replacing rheumatoid arthritis (RA) with type 2 diabetes mellitus (T2DM) in the FRAX algorithm. METHODS: A total of 1,047 patients with T2DM from the Endocrinology Department of the Third Affiliated Hospital of Nanchang University were enrolled in this study. Dual-energy X-ray absorptiometry (DXA) was then used to detect their bone density. RA in the FRAX algorithm was replaced with T2DM, and the new RA-adjusted FRAX was used to assess the fracture risk of the patients. RESULTS: The sensitivity, specificity, and Youden's index of the RA-adjusted FRAX to the treatment opinions on T2DM-associated hip fractures were 0.4761, 0.9642, and 0.4403, respectively, while the sensitivity, specificity, and Youden's index of RA-adjusted FRAX to the treatment opinions on T2DM-associated major bone osteoporotic fractures were 0.0080, 1.0000, 0.0080, respectively. The DXA and RA-adjusted FRAX both showed acceptable consistency in the treatment recommendations for hip fractures in patients with T2DM (κ = 0.49) but had poor consistency in treatment recommendations for major bone osteoporotic fractures (κ = 0.010). The body mass index (BMI) scores, femoral neck-bone mineral densities, and number of males in the same treatment opinion group were significantly higher than in the different treatment opinions group (P < 0.001). CONCLUSION: RA-adjusted FRAX is a useful clinical tool for evaluation of hip fracture risk for Chinese patients with T2DM, and the accuracy of fracture risk prediction for male patients with T2DM and patients with T2DM with high BMI scores or high femoral neck-bone mineral density is higher.
33505478 Efficacy and safety of rituximab in the treatment of connective tissue disease-related int 2021 Interstitial lung disease (ILD) represents a severe pulmonary complication of connective tissue diseases, rheumatoid arthritis (RA), and antineutrophil cytoplasmic antibody-associated vasculitis. Treatment of ILD, mainly based on immunosuppression, remains challenging. Rituximab (RTX), a monoclonal antibody binding to CD20, is considered a valuable therapeutic choice in cases of refractory ILD. Here, we review the available efficacy and safety data on the use of RTX in the treatment of rheumatic disease-related ILD. Despite controversial efficacy data, RTX seems to be able to stabilize or improve ILD related to RA and antisynthetase syndrome and in established and severe ILD complicating systemic sclerosis. Fewer data are available regarding ILD related to Sjögren syndrome, systemic lupus erythematosus, and antineutrophil cytoplasmic antibody-associated vasculitis. To date, few prospective studies are available and randomized trials are still ongoing with the purpose of exploring the role of RTX in this condition, including the supposed relationship between efficacy and ILD radiologic patterns and safety data, up to now derived mainly from RA studies. Despite an overall acceptable safety profile, concerns remain regarding an increased infectious disease risk in patients with ILD as well as possible lung toxicity and the increased rate of immune-mediated reactions in patients with connective tissue diseases. In conclusion, RTX is a relevant therapeutic option for rheumatic disease-related ILD despite the existing uncertainties; ongoing trials are expected to clarify its use.
33370631 Thymoquinone in autoimmune diseases: Therapeutic potential and molecular mechanisms. 2021 Feb Autoimmune diseases (AUDs) are a multifactorial disease, among which rheumatoid arthritis, systemic lupus erythematosus and multiple sclerosis are more prevalent. Several anti-inflammatory, biologics, and AUD-modifying drugs are found effective against them, but their repeated use are associated with various adverse effects. In this review article, we have focused on the regulation of inflammatory molecules, molecular signaling pathways, immune cells, and epigenetics by natural product thymoquinone on AUDs. Studies indicate that thymoquinone can regulate inflammatory molecules including interferons, interleukins, tumor necrosis factor-α (TNF-α), oxidative stress, regulatory T cells, and various signaling pathways such as nuclear factor kappa beta (NF-κβ), janus kinase/signal transduction and activator of transcription (JAK-STAT), mitogen-activated protein kinase (MAPK) at the molecular level and epigenetic alteration. As these molecules and signaling pathways with defective immune function play an important role in AUD development, controlling these molecules and deregulated molecular mechanism is a significant feature of AUD therapeutics. Interestingly thymoquinone is reported to possess all these potential. This article reviewed the deregulated mechanism of AUDs, and the action of thymoquinone on inflammatory molecules, immune cells, signaling pathways, and epigenetic machinery. Thymoquinone can be regarded as a potential drug candidate for AUD treatment.
33360174 Comorbidity in multiple sclerosis patients from Nordland County, Norway - validated data f 2021 Feb BACKGROUND: Knowledge of comorbid disorders is important to optimize therapy for multiple sclerosis (MS), but data are limited. The aim of this study was to assess comorbidity in persons with MS living in Nordland County on January 1, 2017. METHODS: Data were retrieved from the Norwegian Patient Registry (2008-2017) and validated through review of electronic hospital charts (1970-2017). Comorbidity was defined as any distinct disorder, classified in the International Classification of Diseases (ICD-10), that had existed or occurred after the diagnosis of MS was established. RESULTS: Data from 637 subjects were reviewed, and 97.5% were registered with at least one comorbid condition. Malignant melanoma was found in 0.5%, and non-melanoma skin cancers in 1.9%. In female subjects, breast cancer was found in 3.3%. Hypothyroidism was confirmed in 3.1%, type-1 diabetes in 0.3%, type-2 diabetes in 3.9%, psychosis in 0.6%, epilepsy in 2.8%, myocardial infarction in 1.7%, subarachnoid hemorrhage in 0.2%, cerebral infarction in 0.6%, pulmonary embolism in 0.9%, inflammatory bowel disease in 1.3%, and rheumatoid arthritis in 0.6%. CONCLUSION: Compared to reports from other Norwegian epidemiological studies, a higher proportion of inflammatory bowel disease and epilepsy was found. This is in accordance with findings from other studies. The prevalence of non-melanoma skin cancers was significantly higher than in the general Norwegian population as they were reported by The Cancer Registry of Norway.
33249046 Autoantigen-specific immune tolerance in pathological and physiological cell death: Nanote 2021 Jan Apoptotic cells are tolerogenic and can present self-antigens in the absence of inflammation, to antigen-presenting cells by the process of efferocytosis, resulting in anergy and depletion of immune effector cells. This tolerance is essential to maintain immune homeostasis and prevent systemic autoimmune diseases, such as rheumatoid arthritis and systemic lupus erythematosus. Consequently, effective efferocytosis can result in the induction of immune tolerance mediated via triggering modulatory lymphocytes and anti-inflammatory responses. Furthermore, several distinct soluble factors, receptors and pathways have been found to be involved in the efferocytosis, which are able to regulate immune tolerance by lessening antigen presentation, inhibition of T-cell proliferation and induction of regulatory T-cells. Some newly developed nanotechnology-based approaches can induce antigen-specific immunological tolerance without any systemic immunosuppression. These strategies have been explored to reverse autoimmune responses induced against various protein antigens in different diseases. In this review, we describe some nanotechnology-based approaches for the maintenance of self-tolerance using the apoptotic cell clearance process (efferocytosis) that may be able to induce immune tolerance and treat autoimmune diseases.
34394873 Ankylosing Spondylitis. 2021 Jul The seronegative spondyloarthropathies are a group of autoimmune inflammatory diseases lacking rheumatoid factor or antinuclear antibody in their serum. They include ankylosing spondylitis (AS), reactive arthritis, psoriatic arthritis, spondylitis associated with Crohn's disease and ulcerative colitis, and undifferentiated spondyloarthropathies. Inflammation mostly affects the axial joints, entheses, and extra-articular structures such as uveal tract, gastrointestinal tract, mucocutaneous tissue, and heart. Uveitis is the most common extra-articular manifestation. Spondyloarthropathies, especially AS, have a strong association with the presence of Human Leukocyte Antigen (HLA)-B27 gene. AS happens earlier in HLA-B27 patients and men are more prone to the disease. Uveitis, typically unilateral non-granulomatous acute anterior uveitis, occurs in up to 50% of the patients with AS. HLA-B27 positivity correlates with more frequent flare-ups. Conjunctivitis and scleritis are rare ocular manifestations of AS. To establish the diagnosis of AS, at least one clinical and one radiologic parameter are required for definitive diagnosis. Magnetic resonance imaging (MRI) or bone scan can help early detection of the axial skeleton inflammation. The course of eye and joint involvement are not correlated. Short-term treatment with topical corticosteroids and cycloplegic agents control the uveitis attack. In resistant cases, local or systemic therapy with corticosteroids are recommended. NSAIDs, disease-modifying anti-rheumatic drugs (DMARDs), methotrexate, azathioprine, anti-IL-17A monoclonal antibodies, and TNF-α antagonists are effective treatments for ocular and systemic manifestations of AS. If not treated adequately, uveitis may become recalcitrant and extend posteriorly. Functional impairment due to joint destruction can also occur as a result of under-treatment.
33487481 Membranous Nephropathy: Core Curriculum 2021. 2021 Mar The understanding and management of membranous nephropathy, a common cause of nephrotic syndrome that is more frequently encountered in adults than in children, has rapidly evolved over the past decade. Identification of target antigens has allowed for more precise molecular diagnoses, and the ability to monitor circulating autoantibodies has added a new vantage point in terms of disease monitoring and decisions about immunosuppression. Although immunosuppression with alkylating agents combined with corticosteroids, or with calcineurin inhibitor-based regimens, has been the historical mainstay of treatment, observational and now randomized controlled trials with the B-cell-depleting agent rituximab have moved this agent to the forefront of therapy for primary membranous nephropathy. In this Core Curriculum, we discuss the typical features of primary and secondary disease; highlight the target antigens such as the phospholipase A(2) receptor, thrombospondin type 1 domain-containing 7A, neural epidermal growth factor-like 1, and semaphorin-3B; describe the relationship between the immunologic and clinical courses of disease; and review modern management with supportive care or immunosuppressive treatment based on these composite parameters.
33832966 EULAR Points to Consider (PtC) for designing, analysing and reporting of studies with work 2021 Sep BACKGROUND: Clinical studies with work participation (WP) as an outcome domain pose particular methodological challenges that hamper interpretation, comparison between studies and meta-analyses. OBJECTIVES: To develop Points to Consider (PtC) for design, analysis and reporting of studies of patients with inflammatory arthritis that include WP as a primary or secondary outcome domain. METHODS: The EULAR Standardised Operating Procedures were followed. A multidisciplinary taskforce with 22 experts including patients with rheumatic diseases, from 10 EULAR countries and Canada, identified methodologic areas of concern. Two systematic literature reviews (SLR) appraised the methodology across these areas. In parallel, two surveys among professional societies and experts outside the taskforce sought for additional methodological areas or existing conducting/reporting recommendations. The taskforce formulated the PtC after presentation of the SLRs and survey results, and discussion. Consensus was obtained through informal voting, with levels of agreement obtained anonymously. RESULTS: Two overarching principles and nine PtC were formulated. The taskforce recommends to align the work-related study objective to the design, duration, and outcome domains/measurement instruments of the study (PtC: 1-3); to identify contextual factors upfront and account for them in analyses (PtC: 4); to account for interdependence of different work outcome domains and for changes in work status over time (PtC: 5-7); to present results as means as well as proportions of patients reaching predefined meaningful categories (PtC: 8) and to explicitly report volumes of productivity loss when costs are an outcome (PtC:9). CONCLUSION: Adherence to these EULAR PtC will improve the methodological quality of studies evaluating WP.
34964800 Analysis of dental amalgam fillings on primary Sjögren's syndrome: A population-based cas 2021 Nov 24 Primary Sjören's syndrome (pSS) is an autoimmune disease characterized by the inflammatory infiltrate and progressive dysfunction of salivary glands. Dental amalgam with mercury has been raised the public concerns regarding its purported mercury toxicity from dental amalgam to possible systemic inflammatory and immune reactions.In this study, a nationwide population-based database was employed to investigate the association of amalgam filling (AMF) and the risk of pSS. A retrospective case-control study was sourced from the Taiwanese National Health Insurance Research Database (NHIRD) from 2000 to 2013. Case and control groups were matched by sex, age, urbanization level, monthly income, and comorbidities using the propensity score method with a 1:1 ratio. In this study, 5848 cases and 5848 controls were included.The results demonstrated no statistically significant differences between AMF and pSS (odds ratio [OR]: 0.974, 95% confidence interval [CI] = 0.904-1.049). In addition, pSS was also not associated with AMF for women (OR: 0.743, 95% CI = 0.552-1.000) and men (OR: 1.006, 95% CI = 0.670-1.509), respectively.Taken together, evidence demonstrated that the association of AMF and pSS was inconsistent from this robust register databank.
33979588 Six distinct NFκB signaling codons convey discrete information to distinguish stimuli and 2021 May 11 Macrophages initiate inflammatory responses via the transcription factor NFκB. The temporal pattern of NFκB activity determines which genes are expressed and thus, the type of response that ensues. Here, we examined how information about the stimulus is encoded in the dynamics of NFκB activity. We generated an mVenus-RelA reporter mouse line to enable high-throughput live-cell analysis of primary macrophages responding to host- and pathogen-derived stimuli. An information-theoretic workflow identified six dynamical features-termed signaling codons-that convey stimulus information to the nucleus. In particular, oscillatory trajectories were a hallmark of responses to cytokine but not pathogen-derived stimuli. Single-cell imaging and RNA sequencing of macrophages from a mouse model of Sjögren's syndrome revealed inappropriate responses to stimuli, suggestive of confusion of two NFκB signaling codons. Thus, the dynamics of NFκB signaling classify immune threats through six signaling codons, and signal confusion based on defective codon deployment may underlie the etiology of some inflammatory diseases.
33968069 Autoimmune B Cell Repertoire in a Mouse Model of Sjögren's Syndrome. 2021 In genetically prone individuals, chronic immune activation may lead to expansion of autoreactive lymphocyte clones that can induce organ damage developing autoimmune disorders. Sjögren's Syndrome (SjS) is a systemic chronic autoimmune disease that primarily affects exocrine glands. Despite the accumulated evidences of profound B-cell alterations of humoral immunity, the repertoire and development of B-cell autoreactivity in SjS remains to be determined. We hypothesize that SjS mice will have an increased frequency of self-reactive B cells with a progressive evolution to antigen-driven oligoclonality. Here, we study the B cell repertoire of NOD.H-2(h4) mice, a mouse model of spontaneous autoimmunity mimicking SjS without developing diabetes. A library of 168 hybridomas from NOD.H-2(h4) mice and 186 C57BL/6J splenocytes at different ages was created. The presence of mono or polyreactive autoantibodies to several antigens was evaluated by ELISA, and their staining patterns and cellular reactivity were tested by IFA and FACS. We observed a higher frequency of autoreactivity among B-cell clones from NOD.H-2(h4) mice as compared to wild-type mice. The presence of polyreactive and autoreactive IgG clones increased with mice age. Strikingly, all anti-Ro52 autoantibodies were polyreactive. No loss of polyreactivity was observed upon antibody class switching to IgG. There was a progression to oligoclonality in IgG B cells with mice aging. Our results indicate that in the NOD.H-2(h4) mouse model of SjS, IgG+ B cells are mainly polyreactive and might expand following an unknown antigen-driven positive selection process.