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"Disease modification" in axial spondyloarthritis (axSpA) seeks to not only alleviate clinical symptoms but also alter the disease's natural course by impeding new bone formation. Recent years have witnessed the effectiveness of treatments, including biologics and nonsteroidal anti-inflammatory drugs, in managing axSpA symptoms. Emerging evidence points toward their potential impact on slowing structural disease progression. This comprehensive review centers on the pivotal role of inhibiting new bone formation in axSpA disease modification. It delves into the significance of imaging techniques for assessing disease progression and explores the disease-modifying properties of available axSpA treatments, encompassing NSAIDs, TNF inhibitors, IL-17 inhibitors, and JAK inhibitors. This article offers valuable insights into the evolving landscape of disease modification strategies in axial spondyloarthritis, highlighting the multifaceted approaches used to attain these objectives., Competing Interests: Declaration of competing interest None., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Toxoplasma gondii (TOXO) is a neuroinvasive protozoan parasite that induces the formation of persistent cysts in mammalian brains. It infects approximately 1.1million people in the United States annually. Latent TOXO infection is implicated in the etiology of psychiatric disorders, especially schizophrenia (SCZ), and has been correlated with modestly impaired cognition. The acoustic startle response (ASR) is a reflex seen in all mammals. It is mediated by a simple subcortical circuit, and provides an indicator of neural function. We previously reported the association of TOXO with slowed acoustic startle latency, an index of neural processing speed, in a sample of schizophrenia and healthy control subjects. The alterations in neurobiology with TOXO latent infection may not be specific to schizophrenia. Therefore we examined TOXO in relation to acoustic startle in an urban, predominately African American, population with mixed psychiatric diagnoses, and healthy controls. Physiological and diagnostic data along with blood samples were collected from 364 outpatients treated at an inner-city hospital. TOXO status was determined with an ELISA assay for TOXO-specific IgG. A discrete titer was calculated based on standard cut-points as an indicator of seropositivity, and the TOXO-specific IgG concentration served as serointensity. A series of linear regression models were used to assess the association of TOXO seropositivity and serointensity with ASR magnitude and latency in models adjusting for demographics and psychiatric diagnoses (PTSD, major depression, schizophrenia, psychosis, substance abuse). ASR magnitude was 11.5% higher in TOXO seropositive subjects compared to seronegative individuals (p=0.01). This effect was more pronounced in models with TOXO serointensity that adjusted for sociodemographic covariates (F=7.41, p=0.0068; F=10.05, p=0.0017), and remained significant when psychiatric diagnoses were stepped into the models. TOXO showed no association with startle latency (t=0.49, p=0.63) in an unadjusted model, nor was TOXO associated with latency in models that included demographic factors. After stepping in individual psychiatric disorders, we found a significant association of latency with a diagnosis of PTSD (F=5.15, p=0.024), but no other psychiatric diagnoses, such that subjects with PTSD had longer startle latency. The mechanism by which TOXO infection is associated with high startle magnitude is not known, but possible mechanisms include TOXO cyst burden in the brain, parasite recrudescence, or molecular mimicry of a host epitope by TOXO. Future studies will focus on the neurobiology underlying the effects of latent TOXO infection as a potential inroad to the development of novel treatment targets for psychiatric disease., (Copyright © 2016 Elsevier Inc. All rights reserved.)

The nonstructural protein 1 (A/NS1) of influenza A viruses (IAV) harbors several src homology (SH)-binding motifs (bm) that mediate interactions with cellular proteins. In contrast to the sequence variability of the second SH3bm, tyrosine 89, within the SH2bm is a highly conserved residue among IAV strains. This prompted us to evaluate the necessity of this SH2bm for IAV virulence. In an in vivo mouse model, we observed drastic reductions in weight loss, mortality, and virus titers in lung and bronchoalveolar lavage fluid after infection with the mutant virus PR8 A/NS1-Y89F (PR8 Y89F) when compared with wild-type virus (PR8 wt). Concomitantly, we observed decreased inflammation and less severe pathologic changes, reflecting reduced levels of virus titers. At histologic analysis, lungs infected with PR8 wt virus showed widespread destruction of the bronchiolar epithelium, with extensive distribution of virus antigen within tracheal, bronchial, bronchiolar, and alveolar epithelium. In marked contrast, the bronchiolar epithelium after infection with the mutant PR8 Y89F virus was entirely intact, and the severity and extent of viral infection was reduced and strongly restricted to alveoli. These findings demonstrate that change of a single residue of the highly conserved SH2bm within the A/NS1 results in restricted virus spread in mouse lung and strongly reduced virulence, which illustrates the necessity of the SH2bm for IAV-induced pathogenicity., (Copyright © 2012 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)

Since the first biologic agent was tested in the treatment of ankylosing spondylitis (AS), the ability of these therapies to dramatically improve the clinical symptoms and signs of the disease was very evident. Over the past decade, 4 tumor necrosis factor-alpha inhibitors have been approved by the Food and Drug Administration for the treatment of AS. Published data include randomized controlled trials, registries and observational studies. Guidelines have also been developed for the use of biologics in AS. Although a lot is known about the use of biologics in the AS, several "unknowns" remain. Whether these agents can alter the natural history of AS if started very early in the course or whether they can prevent extra-articular manifestations are among the important unanswered questions. Most of the data summarized in this review relate to tumor necrosis factor-alpha inhibitors, and other biologic agents that have been studied are included, as well. This review also summarizes what questions remain about the use of biologics in AS and what type of studies will be required to answer them.