Background: Aggregatibacter actinomycetemcomitans (Aa) is a Gram-negative coccobacillus recognized as a pathogen in periodontitis and infective endocarditis. By producing a toxin (leukotoxin A, LtxA) that triggers global hypercitrullination in neutrophils, Aa has been recently linked to rheumatoid arthritis (RA) pathogenesis. Although mechanistic and clinical association studies implicate Aa infection in the initiation of autoimmunity in RA, direct evidence in humans is lacking.Case:We describe a 59-year-old man with anti-citrullinated protein antibody (ACPA)-positive RA who presented for evaluation of refractory disease. He was found to have Aa endocarditis. Following antibiotic treatment, joint symptoms resolved and ACPAs normalized. Given the implications for RA immunopathogenesis, we further investigated the bacterial, genetic and immune factors that may have contributed to the patient's clinical and autoimmune phenotypes.Methods:DNA was extracted from serum and used to amplify the Aa leukotoxin (ltx) promoter region by PCR, which was further analyzed by Sanger sequencing. High-resolution identification of HLA alleles was performed by sequenced based typing (SBT). TNF-α, IFN-γ, GM-CSF, IL-1β, IL-6, IL-8, IL-17A, IL-18, IL-21, and IL-22 were quantified in serum by a multiplex immunoassay. IgG and IgA antibodies to Aa LtxA were assayed by ELISA.Results:Aa genotyping confirmed infection with a highly leukotoxic strain carrying a 530-bp ltx promoter deletion, shown to result in 10- to 20-fold higher bacterial expression of LtxA. Immuno-phenotyping showed high anti-LtxA antibodies, elevated cytokines implicated in RA pathogenesis (Th1/Th17), and specific host susceptibility conferred by three HLA alleles strongly linked to ACPAs and RA (DRB1*04:04, DRB1*15:01, and DPB1*04:01). One year after eradication of Aa, the patient remained free of arthritis and anti-CCP antibodies.Conclusion: In the context of genetic risk for RA, systemic subacute infection with a leukotoxic strain of Aa can drive ACPA production and a clinical phenotype similar to RA.

Although the current study lends some support to the view that PTA and cognitive factors affect preferred DIR and NR setting, it also indicates that these effects can vary across noise management technologies. To facilitate more personalized HA fittings, future research should investigate the source of this variability.

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HA noise suppression may affect the recognition and recall of speech at positive SNRs, irrespective of individual reading span. Future work should improve the reliability of the auditory working memory measurements.

Olfactory and gustatory disorders are prominent symptoms of acute COVID-19. Although both senses recover in many patients within weeks to months, persistency has been described in up to 60%. However up to now most reports on the course of chemosensitive disorders after COVID-19 are not based on psychophysical testing but only on subjective patients’ ratings. In this study we assessed both olfaction and gustation using psychophysical tests eight months after COVID-19. Validated psychophysical testing revealed hyposmia in 18% and hypogeusia in even 32% of 303 included patients. This shows that olfactory and especially gustatory disorders have to be seen as important chronic symptoms post-COVID-19. The high prevalence of gustatory dysfunction indicates that gustatory function does not recover or might even deteriorate in the months following the acute infection.