Primary Sjögren’s Syndrome: Oral and Ocular Aspects

Temaene for avhandlingen var å vurdere orale og okulære forandringer og oral helserelatert livskvalitet (ved OHIP-14) hos pasienter med primært Sjögrens syndrom. Videre ble forstyrrelser i smak- og luktfunksjon undersøkt, og salivær mikrobiota ble kartlagt ved hjelp av PCR og 16S rRNA gensekvensering. Resultatene fra pasienter med primært Sjögrens syndrom (pSS) ble sammenlignet med pasienter med non-Sjögrens sicca (non-SS), det vil si pasienter som er plaget med tørr munn og tørre øyne men som ikke oppfyller kriteriene for Sjögrens syndrom, og med friske kontrollpersoner. Pasientene hadde betydelig lavere salivasekresjon og mer munntørrhet i følgende rekkefølge: pSS, non-SS, kontroller. Videre fant vi at både pSS og non-SS pasienter hadde større grad av alvorlig tørre øyne enn friske kontroller. Pasienter med pSS hadde også betydelig lavere smak- og luktfunksjon enn kontroller. Oral helserelatert livskvalitet var signifikant dårligere hos pasientene enn hos kontrollene. I mikrobiologistudien observerte vi at de bakterieslekter det var av mest i alle spyttprøvene var Prevotella, Veillonella, Streptococcus, og Haemophilus. Saliva fra pSS pasienter viste tegn til mikrobiell ubalanse (dysbiose). Resultatene viser at tverrfaglig subjektiv og objektiv evaluering av pasienter med tørr munn og tørre øyne er viktig og kan bidra til bedre livskvalitet og pasientomsorg. På sikt kan informasjon om taksonomisk profil av salivær bakterieflora hos pasienter med pSS bidra til utformingen av salivære biomarkører til bruk i tidlig diagnostikk

Autolysis, DNA uptake and recombination: role in Streptococcus mutans competence and biofilm formation

Bacteria in natural environments are most often found attached to surfaces, embedded in an extracellular matrix. The composition of the extracellular matrix includes polysaccharides, proteins and DNA. This mode of growth is associated with differential expression of several genes, including often regulatory genes such as those involved in bacterial cell-to-cell communication. In the biofilm mode, bacteria exhibit increased resistance to antimicrobials and to host defense systems

Dysbiotic salivary microbiota in dry mouth and primary Sjögren’s syndrome patients

Objectives Primary Sjögren’s syndrome (pSS) is an autoimmune disease characterized by reduced lacrimal and salivary secretion. Sicca symptoms together with fatigue and musculoskeletal pain can significantly reduce the patients’ quality of life. Furthermore, low salivary secretion may disrupt the oral microbial homeostasis. The aim of this study was to compare the salivary microbiota from pSS patients with patients with sicca symptoms not fulfilling the classification criteria for pSS (non-SS), and with healthy controls without sicca complaints. Methods Pellets from centrifuged chewing-stimulated whole saliva from pSS patients (n = 15), non-SS sicca patients (n = 15) and healthy controls (n = 15) were prepared. DNA was extracted and analyzed by 16S rRNA gene sequencing. The acquired sequencing data were performed using the human oral microbiome database (HOMD). Results We detected 42, 45, and 34 bacterial genera in saliva samples from pSS patients, non-SS sicca patients, and healthy controls, respectively. The most abundant genera in all samples were Prevotella, Veillonella, Streptococcus, and Haemophilus. At species level Streptococcus intermedius, Prevotella intermedia, Fusobacterium nucleatum subsp. vincentii, Porphyromonas endodontalis, Prevotella nancensis, Tannerella spp., and Treponema spp. were detected in the samples from pSS and non-SS only, while Porphyromonas pasteri was mostly found among the healthy controls. Conclusion Our study indicated dysbiosis in the salivary microbiota from pSS and non-SS patients compared to healthy controls. Additionally, the results showed that the salivary microbiome in the pSS group differed significantly from the non-SS group

Identification of potential saliva and tear biomarkers in primary Sj\uf6gren\u2019s syndrome, utilising the extraction of extracellular vesicles and proteomics analysis

Abstract Background There is a long-lasting need for non-invasive, more accurate diagnostic techniques when evaluating primary Sj\uf6gren\u2019s syndrome (pSS) patients. Incorporation of additional diagnostics involving screening for disease-specific biomarkers in biological fluid is a promising concept that requires further investigation. In the current study we aimed to explore novel disease biomarkers in saliva and tears from pSS patients. Methods Liquid chromatography-mass spectrometry (LC-MS) was performed on stimulated whole saliva and tears from 27 pSS patients and 32 healthy controls, and salivary and tear proteomic biomarker profiles were generated. LC-MS was also combined with size exclusion chromatography to isolate extracellular vesicles (EVs) from both fluids. Nanoparticle tracking analysis was conducted on joint fractions from the saliva and tears to determine size distribution and concentration of EVs. Further EV characterisation was performed by immunoaffinity capture of CD9-positive EVs using magnetic beads, detected by flow cytometry. The LC-MS data were analysed for quantitative differences between patient and control groups using Scaffold, and the proteins were further analysed using the Database for Annotation, Visualization and Integrated Discovery (DAVID), for gene ontology overrepresentation, and the Search Tool for the Retrieval of Interacting Genes/Proteins for protein-protein interaction network analysis. Results Upregulation of proteins involved in innate immunity (LCN2), cell signalling (CALM) and wound repair (GRN and CALML5) were detected in saliva in pSS. Saliva EVs also displayed biomarkers critical for activation of the innate immune system (SIRPA and LSP1) and adipocyte differentiation (APMAP). Tear analysis indicated overexpression of proteins involved in TNF-\u3b1 signalling (CPNE1) and B cell survival (PRDX3). Moreover, neutrophil gelatinase-associated lipocalin was upregulated in saliva and tears in pSS. Consistently, DAVID analysis demonstrated pathways of the adaptive immune response in saliva, of cellular component assembly for saliva EVs, and of metabolism and protein folding in tears in pSS patients. ..

Identification of potential saliva and tear biomarkers in primary Sjögren’s syndrome, utilising the extraction of extracellular vesicles and proteomics analysis

Background There is a long-lasting need for non-invasive, more accurate diagnostic techniques when evaluating primary Sjögren’s syndrome (pSS) patients. Incorporation of additional diagnostics involving screening for disease-specific biomarkers in biological fluid is a promising concept that requires further investigation. In the current study we aimed to explore novel disease biomarkers in saliva and tears from pSS patients. Methods Liquid chromatography-mass spectrometry (LC-MS) was performed on stimulated whole saliva and tears from 27 pSS patients and 32 healthy controls, and salivary and tear proteomic biomarker profiles were generated. LC-MS was also combined with size exclusion chromatography to isolate extracellular vesicles (EVs) from both fluids. Nanoparticle tracking analysis was conducted on joint fractions from the saliva and tears to determine size distribution and concentration of EVs. Further EV characterisation was performed by immunoaffinity capture of CD9-positive EVs using magnetic beads, detected by flow cytometry. The LC-MS data were analysed for quantitative differences between patient and control groups using Scaffold, and the proteins were further analysed using the Database for Annotation, Visualization and Integrated Discovery (DAVID), for gene ontology overrepresentation, and the Search Tool for the Retrieval of Interacting Genes/Proteins for protein-protein interaction network analysis. Results Upregulation of proteins involved in innate immunity (LCN2), cell signalling (CALM) and wound repair (GRN and CALML5) were detected in saliva in pSS. Saliva EVs also displayed biomarkers critical for activation of the innate immune system (SIRPA and LSP1) and adipocyte differentiation (APMAP). Tear analysis indicated overexpression of proteins involved in TNF-α signalling (CPNE1) and B cell survival (PRDX3). Moreover, neutrophil gelatinase-associated lipocalin was upregulated in saliva and tears in pSS. Consistently, DAVID analysis demonstrated pathways of the adaptive immune response in saliva, of cellular component assembly for saliva EVs, and of metabolism and protein folding in tears in pSS patients. Conclusions LC-MS of saliva and tears from pSS patients, solely and in combination with size-exclusion chromatography allowed screening for possible novel biomarkers encompassing both salivary and lacrimal disease target organs. This approach could provide additional diagnostic accuracy in pSS, and could possibly also be applied for staging and monitoring the disease

Interdisciplinary, Comprehensive Oral and Ocular Evaluation of Patients with Primary Sjögren’s Syndrome

Abstract A comprehensive evaluation of oral and ocular symptoms and findings in primary Sjögren’s syndrome (pSS) patients may provide valuable information for management. Medical history was obtained from female pSS patients, and sex- and age-matched non-SS patients with sicca symptoms (non-SS sicca controls) as well as healthy subjects without sicca complaints (healthy controls). Oral (Summated Xerostomia Inventory, SXI) and ocular (McMonnies Dry Eye questionnaire, MDEIS, and Ocular Surface Disease Index, OSDI) subjective complaints were recorded. Objective findings including clinical oral dryness scores (CODS), unstimulated and stimulated saliva secretion rates (UWS/SWS), Schirmer I test, tear osmolarity, tear film break-up time (TFBUT), and ocular surface staining (OSS) were determined. The pSS and non-SS sicca controls were extensively troubled by subjective dryness, while the pSS group had higher CODS, significantly lower saliva and tear secretion, shorter TFBUT and higher OSS than both control groups. Furthermore, candida counts were significantly higher in the pSS patients. In the pSS group, subjective oral dryness significantly correlated with ocular dryness (MDEIS: r = 0.5, OSDI: r = 0.413) and SWS was significantly correlated with Schirmer I (r = 0.419). The findings imply that interdisciplinary subjective and objective evaluation of patients with xerostomia and xerophthalmia not only have implications for patient care, but also may guide clinicians in differentiating between pSS and non-SS sicca patients

“EL MENSAJERO”, CATOLICISMO E INTOLERANCIA RELIGIOSA EN COSTA RICA (1926-1929)

The people who wrote in the newspaper El Mensajero between 1926 to 1929 posed a revision of Catholic dogma, especially in the one the believer must have a personal relationship with God. It was in the criticism of intellectual and political manipulation that the Church promoted - to maintain social control - where they found a strong rejection of the doctrine. Despite the interest of the State about the Costa Rican change or mutate to traditional values to a modern democratic values such as religious tolerance, this did not happen instantly, because it faced the attachment of the Church not to lose its influence in the society.Las personas quienes escribían en el periódico El Mensajero entre 1926 a 1929 planteaban una revisión del dogma católico; principalmente en la cual el creyente debía tener una relación más personal con Dios. Fue en la crítica a la manipulación intelectual y política que la Iglesia promovía – para mantener su control social – en la cual encontraron un fuerte rechazo a su doctrina. Pese al interés del Estado acerca de que el costarricense cambiara o mutara sus valores tradicionales hacia valores democráticos y modernos como la tolerancia religiosa, esto no ocurrió de manera instantánea, debido a que se enfrentó al apego de la Iglesia de no perder su influencia en la socieda