Clinical correlations with Porphyromonas gingivalis antibody responses in patients with early rheumatoid arthritis

Introduction: Prior studies have demonstrated an increased frequency of antibodies to Porphyromonas gingivalis (Pg), a leading agent of periodontal disease, in rheumatoid arthritis (RA) patients. However, these patients generally had long-standing disease, and clinical associations with these antibodies were inconsistent. Our goal was to examine Pg antibody responses and their clinical associations in patients with early RA prior to and after disease-modifying antirheumatic drug (DMARD) therapy. Methods: Serum samples from 50 DMARD-naïve RA patients were tested using an enzyme-linked immunosorbent assay with whole-Pg sonicate. For comparison, serum samples were tested from patients with late RA, patients with other connective tissue diseases (CTDs), age-similar healthy hospital personnel and blood bank donors. Pg antibody responses in early RA patients were correlated with standard RA biomarkers, measures of disease activity and function. Results: At the time of enrollment, 17 (34%) of the 50 patients with early RA had positive immunoglobulin G (IgG) antibody responses to Pg, as did 13 (30%) of the 43 patients with late RA. RA patients had significantly higher Pg antibody responses than healthy hospital personnel and blood bank donors (P < 0.0001). Additionally, RA patients tended to have higher Pg antibody reactivity than patients with other CTDs (P = 0.1), and CTD patients tended to have higher Pg responses than healthy participants (P = 0.07). Compared with Pg antibody-negative patients, early RA patients with positive Pg responses more often had anti-cyclic citrullinated peptide (anti-CCP) antibody reactivity, their anti-CCP levels were significantly higher (P = 0.03) and the levels of anti-Pg antibodies correlated directly with anti-CCP levels (P < 0.01). Furthermore, at the time of study entry, the Pg-positive antibody group had greater rheumatoid factor values (P = 0.04) and higher inflammatory markers (erythrocyte sedimentation rate, or ESR) (P = 0.05), and they tended to have higher disease activity scores (Disease Activity Score based on 28-joint count (DAS28)-ESR and Clinical Disease Activity Index) and more functional impairment (Health Assessment Questionnaire). In Pg-positive patients, greater disease activity was still apparent after 12 months of DMARD therapy. Conclusions: A subset of early RA patients had positive Pg antibody responses. The responses correlated with anti-CCP antibody reactivity and to a lesser degree with ESR values. There was a trend toward greater disease activity in Pg-positive patients, and this trend remained after 12 months of DMARD therapy. These findings are consistent with a role for Pg in disease pathogenesis in a subset of RA patients

Poxvirus Protein N1L Targets the I-κB Kinase Complex, Inhibits Signaling to NF-κB by the Tumor Necrosis Factor Superfamily of Receptors, and Inhibits NF-κB and IRF3 Signaling by Toll-like Receptors

Poxviruses encode proteins that suppress host immune responses, including secreted decoy receptors for pro-inflammatory cytokines such as interleukin-1 (IL-1) and the vaccinia virus proteins A46R and A52R that inhibit intracellular signaling by members of the IL-1 receptor (IL-1R) and Toll-like receptor (TLR) family. In vivo, the TLRs mediate the innate immune response by serving as pathogen recognition receptors, whose oligomerized intracellular Toll/IL-1 receptor (TIR) domains can initiate innate immune signaling. A family of TIR domain-containing adapter molecules transduces signals from engaged receptors that ultimately activate NF-kappaB and/or interferon regulatory factor 3 (IRF3) to induce pro-inflammatory cytokines. Data base searches detected a significant similarity between the N1L protein of vaccinia virus and A52R, a poxvirus inhibitor of TIR signaling. Compared with other poxvirus virulence factors, the poxvirus N1L protein strongly affects virulence in vivo; however, the precise target of N1L was previously unknown. Here we show that N1L suppresses NF-kappaB activation following engagement of Toll/IL-1 receptors, tumor necrosis factor receptors, and lymphotoxin receptors. N1L inhibited receptor-, adapter-, TRAF-, and IKK-alpha and IKK-beta-dependent signaling to NF-kappaB. N1L associated with several components of the multisubunit I-kappaB kinase complex, most strongly associating with the kinase, TANK-binding kinase 1 (TBK1). Together these findings are consistent with the hypothesis that N1L disrupts signaling to NF-kappaB by Toll/IL-1Rs and TNF superfamily receptors by targeting the IKK complex for inhibition. Furthermore, N1L inhibited IRF3 signaling, which is also regulated by TBK1. These studies define a role for N1L as an immunomodulator of innate immunity by targeting components of NF-kappaB and IRF3 signaling pathways

Corporate plagiarism during remote work – a concern?

Plagiarism is a type of academic misconduct that has plagued the education sector for years. It may be one of the most common forms of academic misconducts that is identified in schools (K-12) and higher education sector. Plagiarism is when someone uses someone else’ intellectual property and passes it off as own work without any acknowledgement or attribution.While the topic is well documented and discussed in the academic world, very little is known about how it plays out in the corporate world (Reyman, 2008), except that some studies have shown that students who have a tendency to engage in academic misconduct in academia also demonstrate propensity for unethical practices in the workplace (Khan, al-Qaimari &amp; Samuel, 2007; Daniel et al., 2009).Preliminary discussions during a virtual summit in a Middle Eastern country involving participants from corporate sectors across the region revealed concerns over employees copying and pasting text, code, images and other property when working on company reports or developing digital products. Particular concern arose over “outsourcing” of certain business functions such as “marketing” and “digital content creation”. Some participants shared how they were pressured to create content for clients within unrealistic timeframes and expected to either copy from the web or simply reuse content previous created for other clients. Concerns were focused on corporate sector, but also included administrative staff at educational institutions such as faculty coordinators, marketing and digital content staff, library and registrars’ staff, student services staff, and so on.Majority of concerns discussed revolved around lack of prior knowledge of concepts such as plagiarism among employees during their education career, or copyright and intellectual property infringements; while for educational institutions, the concern was over lack of focus on need to raise awareness among non-faculty staff, beyond courses and subject content.This presentation proposes to look at plagiarism that takes place in the corporate world and how that has become a new concern in the era of remote work due to the COVID19 pandemic, irrespective of the sector the company is in and how academic world can support corporate sector and better prepare future professionals. &nbsp

Autoimmune Arthritides, Rheumatoid Arthritis, Psoriatic Arthritis, or Peripheral Spondyloarthritis Following Lyme Disease

Edificio de uso mixto en la High Line. Manhattan. New York. Convocatoria Abril. Plan 1996. Proyecto fin de carrera. Universidad Politécnica de Madrid. Escuela Técnica Superior de Arquitectur