Variants in the autoimmune disease risk locus influence the regulatory network in immune cells and salivary gland.

Fine mapping and bioinformatic analysis of the genetic risk association in Sjögren's Disease (SjD) and Systemic Lupus Erythematosus (SLE) identified five common SNPs with functional evidence in immune cell types: rs4938573, rs57494551, rs4938572, rs4936443, rs7117261. Functional interrogation of nuclear protein binding affinity, enhancer/promoter regulatory activity, and chromatin-chromatin interactions in immune, salivary gland epithelial, and kidney epithelial cells revealed cell type-specific allelic effects for all five SNPs that expanded regulation beyond effects on and expression. Mapping the local chromatin regulatory network revealed several additional genes of interest, including .

[Sweden can again take the lead in clincal research - if we want to!].

The support systems for Swedish clinical research have been evaluated by the Swedish Research Council and here we summarize some key issues. The shift towards precision medicine and rising requirements for post-registration »real world data« is expected to affect the system for clinical studies. The emerging requirements regarding demonstration of patient value for medical devices need to be better defined.

Aberrant signaling of immune cells in Sjögren's syndrome patient subgroups upon interferon stimulation.

Background: Primary Sjögren's syndrome (pSS) is a systemic autoimmune disease, characterized by mononuclear cell infiltrates in the salivary and lacrimal glands, leading to glandular atrophy and dryness. Patient heterogeneity and lack of knowledge regarding its pathogenesis makes pSS a difficult disease to manage.

Methods: An exploratory analysis using mass cytometry was conducted of MAPK/ERK and JAK/STAT signaling pathways in peripheral blood mononuclear cells (PBMC) from 16 female medication free pSS patients (8 anti-Sjögren's syndrome-related antigen A negative/SSA- and 8 SSA+) and 8 female age-matched healthy donors after stimulation with interferons (IFNs).

Impaired activation of STAT5 upon IL-2 stimulation in Tregs and elevated sIL-2R in Sjögren's syndrome.

Background: Interleukin-2 (IL-2) and the high-affinity IL-2 receptor (IL-2R) are essential for the survival of regulatory T cells (Tregs) which are the main players in immune tolerance and prevention of autoimmune diseases. Sjögren's syndrome (SS) is a chronic autoimmune disease predominantly affecting women and is characterised by sicca symptoms including oral and ocular dryness. The aim of this study was to investigate an association between IL-2R and Treg function in patients with SS of different severity defined by the salivary flow rate.

Genetic variants at the locus are associated with fatigue in Scandinavian patients with primary Sjögren's syndrome.

Objectives: Fatigue is common and severe in primary Sjögren's syndrome (pSS). The aim of this study was to identify genetic determinants of fatigue in pSS through a genome-wide association study.

Methods: Patients with pSS from Norway, Sweden, UK and USA with fatigue and genotype data available were included.

Inflammatory Stratification in Primary Sjögren's Syndrome Reveals Novel Immune Cell Alterations in Patients' Minor Salivary Glands.

There is a critical need to deconvolute the heterogeneity displayed by the minor salivary glands of primary Sjögren's syndrome (pSS) patients. This is challenging primarily because the disease etiology remains unknown. The hypothesis includes that initial events in the disease pathogenesis target the salivary glands, thereby triggering the development of focal infiltrates (≥50 mononuclear cells) and finally germinal center-like structures.

Lipid, fatty acid, carnitine- and choline derivative profiles in rheumatoid arthritis outpatients with different degrees of periodontal inflammation.

Rheumatoid arthritis (RA) and periodontitis are chronic inflammatory diseases with several pathogenic pathways in common. Evidence supports an association between the diseases, but the exact underlying mechanisms behind the connection are still under investigation. Lipid, fatty acid (FA) and metabolic profile alterations have been associated with several chronic inflammatory diseases, including RA and periodontitis.

Corrigendum: Linking the Declarations of Helsinki and of Taipei: Critical Challenges of Future-Oriented Research Ethics.

[This corrects the article DOI: 10.3389/fphar.2020.

Acinar adipose tissue infiltration in salivary gland biopsy is associated with kynurenines-Interferon-γ pathway inflammation biomarkers.

Objectives: Assess if kynurenines metabolites are biomarkers of damage at labial salivary gland biopsy (LSGB).

Methods: This is a cross-sectional study including 99 patients with primary Sjögren's syndrome (AECG 2002 or ACR/EULAR 2017). Kynurenines were measured in plasma using liquid chromatography-tandem mass spectrometry.

Temporomandibular joint pain and associated magnetic resonance findings: a retrospective study with a control group.

Background: To better understand and evaluate clinical usefulness of magnetic resonance imaging (MRI) in diagnosis and treatment of temporomandibular disorders (TMD), parameters for the evaluation are useful.

Purpose: To assess a clinically suitable staging system for evaluation of MRI of the temporomandibular joint (TMJ) and correlate the findings with age and some clinical symptoms of the TMJ.

Material And Methods: Retrospective analysis of 79 consecutive patients with clinical temporomandibular disorder or diagnosed inflammatory arthritis.

Validation of the driver ecological glare test.

Introduction: The present study proposes to validate the Driver Ecological Glare Test (DEGT), a test developed to measure the benefit of a headlight glare Advanced Driver Assistance System (ADAS), by comparing it to a laboratory glare test.

Method: Twenty-four participants, aged from 55 to 70 years, were recruited to complete a visual examination, including monocular halo size measurement for both eyes using Vision Monitor device (MonCv3; Metrovision). An on-field evaluation took place at night at the UTAC CERAM test track to obtain disability glare measures using the DEGT.

Implications of monocular vision for racing drivers.

We performed two experiments to investigate how monocular vision and a monocular generalized reduction in vision (MRV) impact driving performance during racing. A total of 75 visually normal students or professional racing drivers, were recruited for the two experiments. Driving performance was evaluated under three visual conditions: normal vision, simulated monocularity and simulated monocular reduction in vision.

Assessment of major salivary gland ultrasonography in Sjögren's syndrome. A comparison between bedside and post-examination evaluations.

Objectives: Major salivary gland ultrasonography (SGUS) is a suitable diagnostic tool in Sjögren's syndrome (SS). We aimed to determine the more representative gland, projection and format most applicable for reproducible image analysis.

Methods: One investigator performed SGUS in patients with SS.

Single Cell Based Phosphorylation Profiling Identifies Alterations in Toll-Like Receptor 7 and 9 Signaling in Patients With Primary Sjögren's Syndrome.

Primary Sjögren's syndrome (pSS) is associated with polymorphisms and mRNA expression profiles that are indicative of an exaggerated innate and type I IFN immune response. Excessive activation potential of signaling pathways may play a role in this profile, but the intracellular signaling profile of the disease is not well characterized. To gain insights into potentially dysfunctional intracellular signaling profiles of pSS patients we conducted an exploratory analysis of MAPK/ERK and JAK/STAT signaling networks in peripheral blood mononuclear cells (PBMC) from 25 female pSS patients and 25 female age-matched healthy donors using phospho-specific flow cytometry.

Juvenile Sjögren's Syndrome: Clinical Characteristics With Focus on Salivary Gland Ultrasonography.

Objective: Juvenile Sjögren's syndrome (SS) is a rare, poorly defined, and possibly underdiagnosed condition affecting children and adolescents. The aim of this study was to characterize symptoms and clinical findings of juvenile SS and to explore the clinical application of major salivary gland ultrasonography (SGUS) in patients with juvenile SS.

Methods: A cross-sectional multicenter study recruited patients with disease onset until age 18 years (n = 67).

The Shared Ethical Responsibility of Medically and Non-medically Qualified Experts in Human Drug Development Teams.

The complexity of developing and applying increasingly sophisticated new medicinal products has led to the participation of many non-medically qualified scientists in multi-disciplinary non-clinical and clinical drug development teams world-wide. In this introductory paper to the "IFAPP International Ethics Framework for Pharmaceutical Physicians and Medicines Development Scientists" it is argued that all members of such multidisciplinary teams must share the scientific and ethical responsibilities since they all influence directly or indirectly both the outcome of the various phases of the medicines development projects and the safety of the research subjects involved. The participating medical practitioner retains the overriding responsibility and the final decision to stop a trial if the well-being of the research subjects is seriously endangered.

Subgingival microbiome of rheumatoid arthritis patients in relation to their disease status and periodontal health.

Objective: Rheumatoid arthritis (RA) and periodontitis are chronic inflammatory diseases that share common risk factors. However, the bidirectional relationship between RA and periodontal disease is not fully understood. This study was undertaken to describe the bacterial component of the subgingival microbiome in RA patients and to relate this to RA disease activity and periodontal status.

Marine ω-3, vitamin D levels, disease outcome and periodontal status in rheumatoid arthritis outpatients.

Objectives: Marine ω-3 fatty acids (FAs) and Vitamin D (VitD) are reportedly capable of down-regulating inflammation in rheumatoid arthritis (RA) and periodontal disease. This study was undertaken to relate marine FA and VitD status to RA disease status and periodontal conditions.

Methods: RA outpatients (age ≥35 y) were consecutively recruited.

Aberrant cell signalling in PBMCs upon IFN-α stimulation in primary Sjögren's syndrome patients associates with type I interferon signature.

Primary Sjögren's syndrome (pSS) is a complex systemic autoimmune disease with heterogeneous disease manifestations. Genetic predisposition, hormonal and environmental factors are all thought to contribute to disease etiology and pathogenesis. A better understanding of the disease pathogenesis is required in order to establish new targeted therapies.

Long-term follow-up in primary Sjögren's syndrome reveals differences in clinical presentation between female and male patients.

Background: Despite men being less prone to develop autoimmune diseases, male sex has been associated with a more severe disease course in several systemic autoimmune diseases. In the present study, we aimed to investigate differences in the clinical presentation of primary Sjögren's syndrome (pSS) between the sexes and establish whether male sex is associated with a more severe form of long-term pSS.

Methods: Our study population included 967 patients with pSS (899 females and 68 males) from Scandinavian clinical centers.

Identification of a Sjögren's syndrome susceptibility locus at OAS1 that influences isoform switching, protein expression, and responsiveness to type I interferons.

Sjögren's syndrome (SS) is a common, autoimmune exocrinopathy distinguished by keratoconjunctivitis sicca and xerostomia. Patients frequently develop serious complications including lymphoma, pulmonary dysfunction, neuropathy, vasculitis, and debilitating fatigue. Dysregulation of type I interferon (IFN) pathway is a prominent feature of SS and is correlated with increased autoantibody titers and disease severity.