Janicke Cecilie Liaaen Jensen

• Santervas, Leonor Roa; Skovlund, Eva; Ringstad, Ingrid Beate; Kristoffersen, Espen Saxhaug; Fjeld, Katrine Gahre & Hove, Lene Hystad [Show all 9 contributors for this article] (2026). Frailty in relation to general and oral health-related quality of life among older adults in municipal acute care. Journal of Frailty & Aging (JFA). ISSN 2260-1341. 15(5). doi: 10.1016/j.tjfa.2026.100207. Full text in Research Archive Show summary

  Frailty is associated with poorer health-related quality of life (HRQoL) in older adults, but studies rarely assess general and oral HRQoL concurrently in acute care populations. Objectives: To examine the associations between frailty and general as well as oral HRQoL among older adults admitted to a municipal in-patient acute care (MipAC) unit. Design: Cross-sectional study. Setting: Oslo MipAC unit, Norway. Participants: A total of 382 patients aged 70 years or older admitted to the MipAC unit between January and September 2023. Measurements: Frailty was assessed using the Clinical Frailty Scale (CFS). General HRQoL was measured with the 15D instrument and a single-item global life satisfaction question. Oral HRQoL was assessed using the Oral Health Impact Profile-14 (OHIP 14). Associations between frailty and HRQoL were analyzed using linear, ordinal logistic, and binary logistic regression. Exploratory analyses of 15D and OHIP-14 dimensions were performed using non-parametric trend tests. Results: Increasing frailty was significantly associated with lower 15D scores (adjusted B -0.053, 95% CI -0.061 to -0.045), higher odds of lower life satisfaction (adjusted OR 1.19, 95% CI 1.02 to 1.39), and higher odds of reporting oral health impacts on the OHIP-14 (adjusted OR 1.25, 95% CI 1.05 to 1.48). Most 15D dimensions declined with increasing frailty, except distress. For OHIP-14, significant associations were observed for functional limitation, physical pain, and psychological disability. Conclusions: Frailty assessed with the CFS was consistently associated with reduced general and oral HRQoL in older adults admitted to a MipAC unit. These findings support the clinical relevance of simple frailty assessment during acute admission and suggest that it may help identify patients at risk of poorer quality of life.

• Badian, Reza; Sundling, Vibeke; Jensen, Janicke Liaaen; Hynne, Håvard; Tashbayev, Behzod & Hove, Lene Hystad [Show all 8 contributors for this article] (2026). Meibomian Gland Dysfunction and Sex as Risk Factors of Dry Eye Disease in a Cohort of Norwegian 65-year-Olds: A Cross-Sectional Study. Clinical Ophthalmology. ISSN 1177-5467. 20, p. 1–15. doi: 10.2147/opth.s556305. Full text in Research Archive Show summary

  Purpose: Dry eye disease (DED) is a multifactorial condition characterized by the loss of ocular surface homeostasis, causing discomfort and ocular symptoms. Higher age, female sex, and meibomian gland dysfunction (MGD) are some of the reported risk factors for DED. However, age-specific studies of DED are rare. This study aimed to determine the prevalence of DED and MGD in a cohort of Norwegians in their mid-60s. Additionally, to investigate potential sex-related differences in the prevalence of DED and MGD. Methods: For this cross-sectional study, a random sample of 137 demographically homogeneous Norwegian residents of Oslo in their mid-60s was recruited. Participants completed the Ocular Surface Disease Index (OSDI) dry eye symptom questionnaire and underwent clinical dry eye examinations. DED was defined as OSDI ≥ 13, accompanied by fluorescein break-up time (FBUT) < 10s and/or ocular surface staining (OSS) ≥ 1. The presence of MGD was defined as a score of 1 for both meibum quality (MQ) and meibum expressibility (ME) or a score > 1 for either MQ or ME. Results: The overall prevalence for DED was 20.4% [95% CI: 14.0 to 28.2], and for MGD was 90.5% [95% CI: 84.3– 94.9]. No significant sex differences were observed for either condition. MGD was highly prevalent among both DED and non-DED participants: all individuals with DED (n = 28) had MGD, while among those without DED (n = 109), prevalence was 88.1% (males: 85.7%; females: 90.0%). No significant correlation was found between MGD and sex (rs ([137] = [0.075], p = 0.413). In the whole cohort, OPI and FBUT correlated positively with ME (rs ([132] = [0.437] and rs ([132] = [0.296], both p < 0.001) and negatively with OSS (rs ([132] = [− 0.315] and rs ([132] = [0.423], both p< 0.001) and lid margin abnormality (rs ([130] = [− 0.222], p = 0.011; rs ([132] = [0.234], p = 0.007). FBUT correlated also positively with tear production (rs ([128] = [0.308], p< 0.001). A more frequent use of topical ocular lubricant was found among females (p = 0.043). In the symptomatic group, females had significantly lower OPI and FBUT values (p = 0.046 and 0.027, respectively). Among symptomatic participants, categorized as mild (OSDI 13– 22), moderate (OSDI 23– 32), and severe (OSDI 33– 100), only in the severe group did females show higher OSDI scores (p= 0.042) but lower OSS (p= 0.031) compared to males. Conclusion: In this cohort of Norwegians in their mid-60s, DED and MGD were highly and equally prevalent among both sexes. The high prevalence of these conditions underscores the need to raise awareness of DED and MGD within the young elderly population.

• Ringstad, Ingrid Beate; Skovlund, Eva; Santervas, Leonor Roa; Kersten, Hege; Fjeld, Katrine Gahre & Hove, Lene Hystad [Show all 9 contributors for this article] (2026). Association Between Anticholinergic Burden and Dry Mouth Severity in Acutely Ill Older Adults. Drugs & Aging. ISSN 1170-229X. 43(4), p. 361–371. doi: 10.1007/s40266-026-01286-w. Full text in Research Archive Show summary

  Background: Dry mouth is a common and burdensome condition in older adults and its severity may increase with use of anticholinergic medications. The aims were to describe anticholinergic medication use among acutely ill older adults, examine the association between anticholinergic burden and dry mouth severity using the composite Dry Mouth Severity Points (DMSP) measure and investigate whether the association differs by sex. Methods: Patients ≥70 years admitted to Oslo municipal inpatient acute care unit were eligible. Anticholinergic burden (ACB) was assessed using the ACB calculator and classified as 0, lower (ACB = 1-2) or high (ACB = ≥ 3). Dry mouth severity was quantified with DMSP, range 0-4, assigning one point for each indicator above cut-off: General Xerostomia Question ≥ 3, Summated Xerostomia Inventory ≥ 11, Clinical Oral Dryness Score ≥ 6 and unstimulated whole saliva secretion rate ≤ 0.1 mL/min. Associations were examined with ordinal logistic regression. Results: Of 382 examined patients, 256 (mean age 84 ± 7 years, 70% women) had complete data. Mean [standard deviation (SD)] ACB score was 2.0 (1.7); 18% had ACB = 0, 50% had ACB = 1-2 and 32% had ACB = ≥ 3. DMSP scores of 0, 1, 2 and ≥ 3 were present in 29%, 36%, 23% and 12%, respectively. Compared with patients with ACB = 0, those with ACB = 1-2 [odds ratio (OR) = 2.06, 95% confidence interval (CI) 1.07-3.97) and ACB = ≥ 3 (OR = 2.25, 95% CI 1.09-4.63) had higher odds of more severe dry mouth. Women had significantly higher ACB and DMSP scores than men. Conclusions: Even lower anticholinergic burden was associated with greater dry mouth severity, highlighting the need for early recognition and proactive management in acutely ill older adults.

• Santervas, Leonor Roa; Skovlund, Eva; Kristoffersen, Espen Saxhaug; Ringstad, Ingrid Beate; Fjeld, Katrine Gahre & Hove, Lene Hystad [Show all 9 contributors for this article] (2026). Collaborative medication reviews during acute primary care admissions for older adults with polypharmacy: a randomised controlled trial. Age and Ageing. ISSN 0002-0729. 55(2). doi: 10.1093/ageing/afag029. Full text in Research Archive
• Singh, Preet Bano; Singh, Simon Vivan; Iversen, Per Ole & Jensen, Janicke Liaaen (2025). Evaluation and management of chemosensory, trigeminal and salivary dysfunctions in patients with post coronavirus disease. Clinical Nutrition ESPEN. ISSN 2405-4577. 70(December 2025), p. 452–462. doi: 10.1016/j.clnesp.2025.10.018. Full text in Research Archive Show summary

  Background & aims While the management of olfactory disorders among patients with post Coronavirus Disease (COVID-19) is well elucidated, treatment of taste dysfunction, oral burning, and oral dryness is less extensively studied among post-COVID-19 patients. This prospective study aimed (i) to assess the prevalence of chemosensory, trigeminal, and salivary dysfunctions in patients at two different time points following COVID-19 infection, and (ii) to evaluate the recovery process over time. Methods In this cross-sectional study, 54 Early-post-COVID-19 (3–11 months since COVID-19), 46 Late-post-COVID-19 (≥12 months since COVID-19) and 76 Non-COVID-19 controls were recruited. Participants’ olfactory, gustatory, trigeminal, and salivary status were investigated. Depending on the test outcomes, tailored treatments were administered, and patients were monitored every 3–6 months. Results The findings indicated that none of these dysfunctions improved on their own over time. Patients in both post-COVID-19 groups demonstrated significantly reduced smell, trigeminal and salivary functions compared to the control group. Taste impairment was significantly more severe in Late-post-COVID-19 patients compared to Early-post-COVID-19 patients. Follow-up evaluations revealed significant improvement in both smell and taste functions at each follow-up visit across both patient groups. Conclusion Chemosensory, trigeminal, and salivary disorders in post-COVID-19 patients may not resolve with time alone, underscoring the need for tailored treatments to achieve significant improvements.

• Ringstad, Ingrid Beate; Romskaug, Rita; Santervas, Leonor Roa; Fjeld, Katrine Gahre; Hove, Lene Hystad & Skovlund, Eva [Show all 8 contributors for this article] (2025). Oral Health, Xerogenic Medications, and Frailty in Acutely Ill Older Adults. Journal of The American Geriatrics Society. ISSN 0002-8614. 73(8), p. 2466–2474. doi: 10.1111/jgs.19564. Full text in Research Archive Show summary

  Background Oral health is an essential part of overall health and well-being in older adults and may be influenced by medications and frailty. This study aimed to describe the prevalence of xerostomia and hyposalivation and examine their associations with xerogenic medications and frailty in acutely ill older adults. Methods This cross-sectional study included patients aged ≥ 70 years admitted to the Municipal In-Patient Acute Care unit in Oslo, Norway. General xerostomia was defined as a score ≥ 3 on the General Xerostomia Question (GXQ). Specific xerostomia was measured with the Summated Xerostomia Inventory (SXI). Objective dry mouth measures included unstimulated whole saliva (UWS) secretion rate and the Clinical Oral Dryness Score (CODS), with hyposalivation defined as UWS ≤ 0.1 mL/min. Examination of dentition included numbers of missing teeth and posterior occluding pairs of teeth. Medication data included total drug burden and number of xerogenic medications. Frailty was assessed using the Clinical Frailty Scale (CFS). Associations were analyzed using logistic regression models. Results Among 382 patients (mean age 84 years, 72% women), general xerostomia was present in 30% and hyposalivation in 56%. Mean number (SD) of xerogenic medications was 3.7 (±2.2). The number of xerogenic medications used was significantly associated with general xerostomia in both unadjusted (OR: 1.17, 95% CI: 1.05–1.29) and adjusted models (OR: 1.13, 95% CI: 1.01–1.26). Median UWS declined numerically with increasing number of xerogenic medications. Higher CFS scores were associated with increased subjective xerostomia scores (GXQ and SXI), elevated CODS, more missing teeth, and reduced occlusion, but not with general xerostomia or hyposalivation when predefined cut-off values were applied. Conclusion Xerostomia and hyposalivation were common among acutely ill older adults. General xerostomia was associated with xerogenic medication use and frailty. Our findings highlight the need to incorporate oral health assessments into routine geriatric care and emphasize the importance of interdisciplinary collaborations.

• Wiley, Mandi M.; Radziszewski, Marcin; Khatri, Bhuwan; Joachims, Michelle L.; Tessneer, Kandice L. & Stolarczyk, Anna M. [Show all 80 contributors for this article] (2025). Variants in the DDX6-CXCR5 autoimmune disease risk locus influence the regulatory network in immune cells and salivary gland. Annals of the Rheumatic Diseases. ISSN 0003-4967. 84(9), p. 1512–1527. doi: 10.1016/j.ard.2025.04.023. Full text in Research Archive Show summary

  Objectives: Sjögren’s disease (SjD) and systemic lupus erythematosus (SLE) share genetic risk at the DDX6-CXCR5 locus (11q23.3). Identifying and functionally characterising shared SNPs spanning this locus can provide new insights into common genetic mechanisms of autoimmunity. Methods: Transdisease meta-analyses, fine-mapping, and bioinformatic analyses prioritised shared likely functional single nucleotide polymorphisms (SNPs) for allele-specific and cell type–specific functional interrogation using electromobility shift, luciferase reporter, and quantitative chromatin conformation capture assays and clustered regularly interspaced short palindromic repeat (CRISPR) gene regulation. Results: Five shared SNPs were identified as likely functional in primary human immune cells, salivary gland and kidney tissues: rs57494551, rs4936443, rs4938572, rs7117261, and rs4938573. All 5 SNPs exhibited cell type-specific and allele-specific effects on nuclear protein binding affinity and enhancer/promoter regulatory activity in immune, salivary gland epithelial, and kidney epithelial cell models. Mapping of chromatin–chromatin interactions revealed a chromatin regulatory network that expanded beyond DDX6 and CXCR5 to include PHLDB1, lnc-PHLDB1-1, BCL9L, TRAPPC4, among others. Coalescence of functional assays and multiomic data analyses indicated that these SNPs likely modulate the activity of 3 regulatory regions: intronic rs57494551 regulatory region, intergenic SNP haplotype (rs4938572, rs4936443, and rs7117261) regulatory region, and rs4938573 regulatory region upstream of the CXCR5 promoter. Conclusions: Shared genetic susceptibly at the DDX6-CXCR5 locus in SjD and SLE likely alters common mechanisms of autoimmunity, including interferon signalling (DDX6), autophagy (TRAPPC4), and lymphocytic infiltration of disease-target tissues (CXCR5). Further, using multiomic data from patients with SjD, combined with bioinformatic and in vitro functional studies, can provide mechanistic insights into how genetic risk influences the biological pathways that drive complex autoimmunity.

• Tashbayev, Behzod; Badian, Reza; Chen, Xiangjun; Vitelli, Valeria; Lagali, Neil & Dartt, Darlene [Show all 9 contributors for this article] (2025). Comparison of non-invasive and fluorescein tear film break-up time in a 65-year-old Norwegian population: a cross-sectional study. BMJ Open. 15. doi: 10.1136/bmjopen-2024-090305. Full text in Research Archive Show summary

  Objectives Measurement of tear film stability is central in dry eye disease (DED) diagnosis. In this study, we aimed to compare the performance of two methods of tear film stability measurement: non-invasive tear break-up time (NIBUT) and fluorescein tear film break-up time (FTBUT). Design Cross-sectional study. Setting and participants The study involved 132 subjects of 65-year-old inhabitants of the Oslo region who were not seeking ophthalmic care. Interventions The participants underwent a battery of DED tests, including NIBUT measured on Oculus Keratograph 5M and a traditional method using fluorescein drops (FTBUT). Oculus Keratograph 5M measures two types of NIBUT:; appearance time of the first dry spot (NIBUTFirst) and average NIBUTAvg. Results 74 participants (56%) were female and 58 were male (44%). Subjects presented with varying degrees of DED signs and symptoms. Mean values of NIBUTFirst and FTBUT from all the participants were significantly different (6.2±4.9 s vs 8.6±6.2 s, p<0.0001). There was also a significant difference between NIBUTFirst and NIBUTAvg values (6.2±4.9 s vs 8.3±5.5 s, p<0.0001). In contrast, no difference was observed between FTBUT and NIBUTAvg values (8.6±6.2 s vs 8.3±5.5 s, p=0.655). The receiver operating characteristic curve analysis was performed to compare NIBUT and FTBUT in regards to other clinical tests (Ocular Surface Disease Index, ocular surface staining, blink interval, eye redness, corneal sensitivity, lid debris, Schirmer I test, tear osmolarity, meibum quality, meibum expressibility, lid hyperemia, tear meniscus height,. irregular lid margin, conjunctival hyperaemia, margin telangiectasia, lipid layer and meibomian gland drop-out). While FTBUT demonstrated results with area under the curve>0.6, neither NIBUTFirst nor NIBUTAvg showed significant results. Conclusion NIBUTFirst was shorter than FTBUT. Low correlation between NIBUT and FTBUT indicates that these diagnostic tests are not interchangeable. Other DED tests had correlation, though low, while NIBUT did not demonstrate correlation.

• Pedersen, Anne Marie Lynge; Skarstein, Kathrine; Çevik-Aras, Hülya; Kullaa, Arja M.; Laine, Hanna & Jensen, Janicke Liaaen (2024). Sygdomme og tilstande der påvirker spytkirtlerne og deres funktion. Den norske tannlegeforenings Tidende. ISSN 0029-2303. 134(1), p. 28–37. doi: 10.56373/2024-1-6. Full text in Research Archive
• Borge, Hanne; Ringstad, Ingrid Beate; Aqrawi, Lara A.; Fromreide, Siren; Dongre, Harsh Nitin & Galtung, Hilde [Show all 8 contributors for this article] (2024). Increased expression of CXCL10 and CCL3 salivary gland chemokines in primary Sjögren’s syndrome detected and systematically quantified using RNAscope® in situ hybridization. Clinical and Experimental Immunology. ISSN 0009-9104. 219(1). doi: 10.1093/cei/uxae087. Full text in Research Archive Show summary

  Primary Sjögren’s syndrome is a chronic inflammatory disease characterized by the destruction of exocrine glands. We have previously shown significantly upregulated levels of CXCL10 and CCL3 chemokines in saliva from Sjögren’s syndrome patients. In this study, we examined the expression pattern and localization of these chemokines at the site of inflammation in patients’ minor salivary glands using novel RNAscope® in situ hybridization. Minor salivary glands from 33 primary Sjögren’s syndrome patients and 22 non-Sjögren’s syndrome (non-SS) sicca controls were included. The biopsies were formalin-fixed, paraffin-embedded, and histopathologically evaluated. The CXCL10 and CCL3 mRNA expression in the glandular tissue was investigated using reverse transcription quantitative real-time polymerase chain reaction followed by an RNAscope® in situ hybridization. The mRNA expression of CXCL10 was higher than CCL3 in all patients. Significantly elevated expression of CXCL10 and CCL3 was detected in patients that also expressed autoantibody positivity and a positive biopsy for mononuclear cell infiltrates when compared with non-SS sicca controls. CXCL10 was localized as clusters within focal infiltrates as well as adjacent to acinar and ductal epithelium, while CCL3 was expressed as scattered single mRNA molecules in focal infiltrates and in acinar cells. Our findings suggest CXCL10 as a possible disease biomarker in primary Sjögren’s syndrome due to its upregulated expression in both saliva and minor salivary glands of patients and the localization in the tissue. This should be re-assessed in a larger primary Sjögren’s syndrome patient cohort, followed by additional functional studies to further validate its potential as a disease biomarker.

• Uddin, Shahad; Holm, Håkon Forbord; Rahel, Arian; Skarstein, Kathrine; Jensen, Janicke Liaaen & Hynne, Håvard (2024). Sjögren’s Syndrome: The Role of Serological Profiles Versus Minor Salivary Gland Histopathology. Applied Sciences. 14(24). doi: 10.3390/app142411482. Full text in Research Archive Show summary

  Between the years 2008 and 2023, 306 patients were referred to the Department of Oral Surgery and Oral Medicine, Faculty of Dentistry, University of Oslo, for salivary gland biopsy after clinical suspicion of Sjögren’s syndrome. This study aimed to investigate possible associations between serology and minor salivary gland histopathology by stratifying patients according to serology features (negative, single, or double seropositivity according to anti-SSA and anti-SSB), focus score (FS, negative, or actual score), and germinal centers (GCs). Information was collected from referrals and visits. Collected information included oral and ocular dryness symptoms, sialometry, Schirmer I test, histopathological analysis, and serological findings. Patients were classified using the 2002 American European Consensus Group classification criteria and were stratified into seven subgroups according to their serological profiles and FS, which were compared. The majority of patients were females, and the most frequently referred age group was 50–59 years of age. Most patients had both oral and ocular symptoms. Seropositive patients had higher median FS compared to seronegative patients. Double-seropositive patients had significantly higher median FS compared to single-seropositive patients. The results indicated that anti-SSB together with anti-SSA plays a role in disease severity in the salivary glands. In addition to anti-SSA, anti-SSB should be routinely evaluated as a possible predictor of the severity of inflammatory destruction in the salivary gland tissue.

• Fugmann, Cecilia; Reid, Sarah; Pucholt, Pascal; Kvarnström, Marika; Björk, Albin & Mofors, Johannes [Show all 25 contributors for this article] (2024). A high polygenic risk score is associated with SSA/SSB antibody positivity and early onset in primary Sjögren’s disease. Rheumatology. ISSN 1462-0324. doi: 10.1093/rheumatology/keae693. Full text in Research Archive Show summary

  Objectives To calculate a polygenic risk score (PRS) based on single nucleotide variants (SNVs) previously associated with primary Sjögren’s disease (SjD) with genome-wide significance and determine the genetic risk for SjD stratified by antibodies, sex and age at diagnosis. Methods Patients with SjD (n = 1065) were genotyped using Illumina OmniExpressExome chip. Control genotype data were available (n = 7742). Two PRSs were constructed, one including HLA gene variants (n = 21 SNVs), and one without HLA (n = 18 SNVs). High PRS quartile (Q4) individuals were compared with low PRS (Q1–3). Results A high PRS was associated with SSA antibody-positive SjD (OR 9.16, 95% CI 7.75–10.85, P = 3.7 × 10−146), and strengthened in SjD positive for both SSA/SSB antibodies (OR 13.67, 95% CI 10.88–17.32, P = 4.6 × 10−108). High PRS classified SSA/SSB antibody-positive SjD with very good accuracy (AUC 0.86). PRS without HLA showed a weaker association with SSA/SSB positive SjD (OR 2.09, 95% CI 1.71–2.55, P = 6.4 × 10−13). Antibody negative SjD displayed a PRS similar to controls. Patients in the high PRS quartile were significantly younger at diagnosis, 48.9 ± 14.9 vs 53.4 ± 13.4 years in the low PRS quartiles (Q1–3), P = 2.2 × 10−6, and presented higher frequencies of ANA, SSA and SSA/SSB antibodies, P < 1 × 10−5. Conclusion A high PRS is associated with SSA/SSB antibody positivity and early disease onset, both largely attributed to the weight of the HLA alleles. Integration of PRS with other biomarkers applied to clinical phenotypes could be a useful tool for disease risk stratification and treatment decisions.

• Sødal, Anne Thea Tveit; Diep, My Tien; Skudutyte-Rysstad, Rasa; Singh, Preet Bano; Young, Alix & Jensen, Janicke Liaaen [Show all 9 contributors for this article] (2024). Oral helse blant 65-åringer i Oslo. Den norske tannlegeforenings Tidende. ISSN 0029-2303. 12(134). doi: 10.56373/2024-12-5. Full text in Research Archive
• Rogn, Åsmund; Jensen, Janicke Liaaen; Iversen, Per Ole & Singh, Preet Bano (2024). Post-COVID-19 patients suffer from chemosensory, trigeminal, and salivary dysfunctions. Scientific Reports. 14. doi: 10.1038/s41598-024-53919-y. Full text in Research Archive Show summary

  Recent literature indicates that post-COVID-19 patients suffer from a plethora of complications, including chemosensory dysfunction. However, little attention has been given to understand the interactions between chemosensory, trigeminal, and salivary dysfunctions in these patients. The aims of this study were (1) to investigate the prevalence and combinations of chemosensory, trigeminal, and salivary dysfunctions, (2) to identify the odorants/tastants that are compromised, and (3) to explore possible associations between the four dysfunctions in post-COVID-19 patients. One hundred post-COVID-19 patients and 76 healthy controls (pre-COVID-19) were included in this cross-sectional, case-controlled study. Participants' smell, taste, trigeminal, and salivary functions were assessed. The patients had a significantly higher prevalence of parosmia (80.0%), hyposmia (42.0%), anosmia (53.0%), dysgeusia (34.0%), complete ageusia (3.0%), specific ageusia (27.0%), dysesthesia (11.0%) and dry mouth (18.0%) compared to controls (0.0% for all parameters, except 27.6% for hyposmia). Complete loss of bitter taste was the most prevalent specific ageusia (66.7%) and coffee was the most common distorted smell (56.4%). Seven different combinations of dysfunction were observed in the patients, the most common being a combination of olfactory and gustatory dysfunction (48.0%). These findings indicate that post-COVID-19 patients experience a range of chemosensory, trigeminal, and salivary disturbances, occurring in various combinations.

• Frigaard, Julie Mari; Hynne, Håvard; Randsborg, Karoline; Mellin-Olsen, Tonje; Hofgaard, Anne Kristine & Young, Alix [Show all 10 contributors for this article] (2023). Exploring oral health indicators, oral health-related quality of life and nutritional aspects in 23 medicated patients from a short-term psychiatric ward. Frontiers in Public Health. 11. doi: 10.3389/fpubh.2023.1083256. Full text in Research Archive Show summary

  Background Patients suffering from psychiatric disorders face many difficulties due to their condition, medications and lifestyle. Oral health and nutrition may be affected, further complicating their lives. Our aim was to provide in-depth information on oral health and nutritional factors in a small group of patients in short-term psychiatric ward. Methods Twenty-three patients (mean age 36, average medications five) were recruited during short-term hospitalization in a psychiatric ward. Inclusion criteria: anxiety, psychosis and/or depression, and use of at least one antidepressant or anxiolytic/antipsychotic drug with xerostomia as a known side effect. Subjective oral dryness was evaluated using the Shortened Xerostomia Inventory (SXI). Oral examination included Clinical Oral Dryness Score (CODS), secretion of unstimulated (UWS) and stimulated whole saliva (SWS), and evaluation of dental, gingival, and periodontal status. Self-reported complaints of oral disorders were recorded. The Oral Health Impact Profile-14 (OHIP-14) was used to explore oral health-related quality of life. Nutritional status was assessed using the Patient-Generated Subjective Global Assessment Short Form (PG-SGA-SF), and diet quality was assessed using the Mediterranean diet score (KIDMED). Results Compared to healthy controls, the patients had significantly higher SXI scores and CODS, and SWS secretion was lower. Complaints of dysgeusia and halitosis were significantly more frequent among patients. Gingivitis was more common in patients. OHIP-14 scores were much higher in the patients, and they reported significantly poorer oral and general health. Most patients lacked a regular meal pattern. Very low diet quality was observed in five patients, while improvements were needed in twelve. “ Dry mouth ” and “ No appetite, just did not feel like eating ” were the most common symptoms preventing patients from eating enough. The PG-SGA-SF symptoms component score showed a strong negative correlation with self-reported oral health, and a strong positive correlation with OHIP-14. Conclusion This relatively small group of patients in short-term psychiatric ward had both reduced oral health and poor oral health-related quality of life. Furthermore, their nutritional intake was affected by their oral health problems. Although larger groups need to be studied, these findings indicate that oral health and nutrition should be evaluated and adjusted in these patients to improve their overall care.

• Cross, Tanya; Haug, Kari Bente Foss; Brusletto, Berit; Ommundsen, Stine Kamilla; Siebke, Anne-Marie & Aspelin, Trude [Show all 12 contributors for this article] (2023). Non-Coding RNA in Salivary Extracellular Vesicles: A New Frontier in Sjögren’s Syndrome Diagnostics? International Journal of Molecular Sciences. ISSN 1661-6596. 24(17). doi: 10.3390/ijms241713409. Full text in Research Archive Show summary

  Sjögren’s syndrome is an autoimmune rheumatic disease characterized by inflammation of the salivary and lacrimal glands, often manifesting as dry mouth and dry eyes. To simplify diagnostics of primary Sjögren’s syndrome (pSS), a non-invasive marker is needed. The aim of the study was to compare the RNA content of salivary extracellular vesicles (EVs) between patients with pSS and healthy controls using microarray technology. Stimulated whole saliva was collected from 11 pSS patients and 11 age-matched controls. EV-RNA was isolated from the saliva samples using a Qiagen exoRNeasy Midi Kit and analyzed using Affymetrix Clariom D™ microarrays. A one-way ANOVA test was used to compare the mean signal values of each transcript between the two groups. A total of 9307 transcripts, coding and non-coding RNA, were detected in all samples. Of these transcripts, 1475 showed statistically significant differential abundance between the pSS and the control groups, generating two distinct EV-RNA patterns. In particular, tRNAs were downregulated in pSS patients, with the transcript tRNA-Ile-AAT-2-1 showing a 2-fold difference, and a promise as a potential biomarker candidate. This study therein demonstrates the potential for using salivary EV-RNA in pSS diagnostics.

• Frigaard, Julie Mari; Jensen, Janicke Liaaen; Galtung, Hilde & Hiorth, Marianne (2023). Stability and cytotoxicity of biopolymer-coated liposomes for use in the oral cavity. International Journal of Pharmaceutics. ISSN 0378-5173. 645. doi: 10.1016/j.ijpharm.2023.123407. Full text in Research Archive Show summary

  This study investigates the stability and cytotoxicity of biopolymer-coated liposomes for use in the oral cavity. Liposomes (3 mM and 6 mM) were prepared by the thin film method and hydrated with phosphate buffer (PB) or glycerol phosphate buffer (G-PB). For coating, liposomes were added to a biopolymer solution of opposite charge. Particle stability was evaluated by measuring the size, polydispersity index, and zeta potential for up to 60 weeks. In vitro interaction of fluorescent-labelled biopolymer-coated liposomes and dysplastic oral keratinocytes was analyzed by confocal microscopy. Potential cytotoxicity was assessed in dysplastic oral keratinocytes by cell proliferation and cell viability. All three biopolymers showed good coating abilities for both concentrations and hydration media. The alginate coated liposomes in PB, 3 mM chitosan-coated liposomes in PB, and chitosan-coated liposomes in G-PB were stable for up to 60 weeks. In vitro studies demonstrated low cytotoxicity for all coated liposomes and non-specific cellular uptake of biopolymer-coated liposomes, independent of biopolymer, surface charge, lipid concentration and hydration media. All three formulations demonstrated low cytotoxicity and were considered safe. Alginate- and chitosan-coated liposomes demonstrated good stability over time and may be promising agents for use in the oral cavity and should be investigated further.

• Storås, Andrea; Fineide, Fredrik; Magnø, Morten Schjerven; Thiede, Bernd; Chen, Xiangjun & Strumke, Inga [Show all 11 contributors for this article] (2023). Using machine learning model explanations to identify proteins related to severity of meibomian gland dysfunction. Scientific Reports. 13(1). doi: 10.1038/s41598-023-50342-7. Full text in Research Archive Show summary

  Meibomian gland dysfunction is the most common cause of dry eye disease and leads to significantly reduced quality of life and social burdens. Because meibomian gland dysfunction results in impaired function of the tear film lipid layer, studying the expression of tear proteins might increase the understanding of the etiology of the condition. Machine learning is able to detect patterns in complex data. This study applied machine learning to classify levels of meibomian gland dysfunction from tear proteins. The aim was to investigate proteomic changes between groups with different severity levels of meibomian gland dysfunction, as opposed to only separating patients with and without this condition. An established feature importance method was used to identify the most important proteins for the resulting models. Moreover, a new method that can take the uncertainty of the models into account when creating explanations was proposed. By examining the identified proteins, potential biomarkers for meibomian gland dysfunction were discovered. The overall findings are largely confirmatory, indicating that the presented machine learning approaches are promising for detecting clinically relevant proteins. While this study provides valuable insights into proteomic changes associated with varying severity levels of meibomian gland dysfunction, it should be noted that it was conducted without a healthy control group. Future research could benefit from including such a comparison to further validate and extend the findings presented here.

• Frigaard, Julie Mari; Hynne, Håvard & Jensen, Janicke Liaaen (2023). Development and Proposal of a Novel Scoring System to Classify Dry Mouth Severity. Applied Sciences. 13(21). doi: 10.3390/app132111758. Full text in Research Archive Show summary

  Dry mouth is a common complaint with unmet treatment needs, reflected by the fact that more than 500 trials are registered on ClinicalTrials.gov. Comparisons across studies, however, are difficult as inclusion criteria vary widely. Additionally, the terms xerostomia and hyposalivation are often not separated. Thus, the aim of the present work was to develop a dry mouth severity score (DMSS) that incorporates published questionnaires and measures both xerostomia and hyposalivation and proposes a grading system that can be used as a common basis for inclusion into clinical trials. The DMSS was developed through the use of data from patients in the Dry Mouth Clinic, University of Oslo, Norway. Five groups of patients (n = 131) and controls (n = 59) were included: primary Sjögren’s syndrome, non-Sjögren’s syndrome, radiated head and neck cancer, psychiatry, and controls. The proposed DMSS includes five parameters with corresponding cut-off values given 1 point (p) each: the General Xerostomia Question ≥ 2, Summated Xerostomia Inventory ≥ 11, Clinical Oral Dryness Score ≥ 6, and secretion of unstimulated and chewing-stimulated whole saliva with cut-off values at ≤0.1 mL/min and ≤0.7 mL/min, respectively. The proposed score range for DMSS is 0–3, where score 0 corresponds to 0p, score 1 to 1–2p, score 2 to 3p, and score 3 to 4–5p. In the patient group, 65% had a high DMSS of 2 or 3, while 78% of the controls scored 0. The sensitivity and specificity were high (0.93 and 0.78, respectively), and the internal reliability was satisfactory (Cronbach’s alpha 0.80). The proposed DMSS represents a novel method to uniformly classify dry mouth patients for applicable comparison between clinical trials.

• Fineide, Fredrik; Tashbayev, Behzod; Elgstøen, Katja B. Prestø; Sandås, Elise Mørk; Rootwelt, Helge & Hynne, Håvard [Show all 12 contributors for this article] (2023). Tear and Saliva Metabolomics in Evaporative Dry Eye Disease in Females. Metabolites. 13(11). doi: 10.3390/metabo13111125. Full text in Research Archive Show summary

  Accurate diagnosis of dry eye disease (DED) is challenging, and even today there is no gold standard biomarker of DED. Hypothesis-free global metabolomic studies of tears from DED patients have great potential to discover metabolites and pathways affected in the pathophysiology of DED, and to identify possible future biomarkers. These metabolites and biomarkers could be important for diagnosing and monitoring disease as well as for new therapeutic targets and strategies. As DED is associated with dry mouth, this study aimed to perform metabolomic analyses of tears and saliva from patients with decreased tear film break-up time but normal Schirmer test, and age-matched controls with both tear production and stability within physiological range. We applied strict inclusion criteria to reduce sampling bias in the metabolomic analyses and selected only age-matched females with Schirmer test values between 10–15 mm/5 min. The tear film analysis arm included 19 patients (with tear film break-up time 0–5 s) and 12 controls (with tear film break-up time 10–30 s), while the salivary analysis arm consisted of a subset which included 18 patients and six controls. Metabolomic analyses were performed using liquid chromatography and high-resolution mass spectrometry. Analyses using a global database search detected a total of 56 metabolites in tear samples that were significantly different between the groups. Of these, several have known associations with DED. These metabolites are present in meibum and have anti-oxidative characteristics or associations with the ocular microbiome, and altered concentrations suggest that they may play a significant role in DED associated with decreased tear film stability. In saliva, hypotaurine levels were lower among patients with tear film instability. In this pilot study, we found different levels of several metabolites in patients with decreased tear film break-up time that may have associations with DED. Future studies are required to replicate our findings and clarify the exact roles of these metabolites.

• Hynne, Håvard; Tashbayev, Behzod; Diep, My Tien; Sødal, Anne Thea Tveit; Badian, Reza & Chen, Xiangjun [Show all 10 contributors for this article] (2022). The relationship between ocular and oral dryness in a cohort from the 65-year-old population in Norway. Scientific Reports. 12(1). doi: 10.1038/s41598-022-13985-6. Full text in Research Archive Show summary

  In the present study, the relationship between dry eyes and dry mouth was explored in 150 65-year-old subjects randomly selected from the general population in Oslo, Norway. The number of drugs, including xerogenic drugs, and current and previous systemic diseases were recorded. Ocular parameters recorded were the McMonnies Dry Eye Questionnaire, the Ocular Surface Disease Index, the Schirmer I Test, tear film break-up time and ocular surface staining. The oral parameters were xerostomia frequency, Summated Xerostomia Inventory, Clinical Oral Dryness Score, and unstimulated and stimulated whole saliva. The participants with current or previous systemic diseases had significantly more ocular and oral symptoms and significantly more oral clinical findings than the participants without a history of disease. Moreover, correlation and factor analyses demonstrated an association between subjective ocular and oral parameters. A significant correlation between the total number of drugs and the presence of ocular and oral symptoms was also noted. When the participants were categorized based on their ocular symptoms, poorer values were found for the oral parameters among the participants more troubled with dry eyes. The results in the present study call for increased awareness and an interdisciplinary approach in matters related to dry eyes and dry mouth.

• Lundtoft, Christian; Pucholt, Pascal; Martin, Myriam; Bianchi, Matteo; Lundström, Emeli & Eloranta, Maija-Leena [Show all 49 contributors for this article] (2022). Complement C4 Copy Number Variation is Linked to SSA/Ro and SSB/La Autoantibodies in Systemic Inflammatory Autoimmune Diseases. Arthritis & Rheumatology. ISSN 2326-5191. 74(8), p. 1440–1450. doi: 10.1002/art.42122. Full text in Research Archive Show summary

  Objective Copy number variation of the C4 complement components, C4A and C4B, has been associated with systemic inflammatory autoimmune diseases. This study was undertaken to investigate whether C4 copy number variation is connected to the autoimmune repertoire in systemic lupus erythematosus (SLE), primary Sjögren's syndrome (SS), or myositis. Methods Using targeted DNA sequencing, we determined the copy number and genetic variants of C4 in 2,290 well-characterized Scandinavian patients with SLE, primary SS, or myositis and 1,251 healthy controls. Results A prominent relationship was observed between C4A copy number and the presence of SSA/SSB autoantibodies, which was shared between the 3 diseases. The strongest association was detected in patients with autoantibodies against both SSA and SSB and 0 C4A copies when compared to healthy controls (odds ratio [OR] 18.0 [95% confidence interval (95% CI) 10.2–33.3]), whereas a weaker association was seen in patients without SSA/SSB autoantibodies (OR 3.1 [95% CI 1.7–5.5]). The copy number of C4 correlated positively with C4 plasma levels. Further, a common loss-of-function variant in C4A leading to reduced plasma C4 was more prevalent in SLE patients with a low copy number of C4A. Functionally, we showed that absence of C4A reduced the individuals’ capacity to deposit C4b on immune complexes. Conclusion We show that a low C4A copy number is more strongly associated with the autoantibody repertoire than with the clinically defined disease entities. These findings may have implications for understanding the etiopathogenetic mechanisms of systemic inflammatory autoimmune diseases and for patient stratification when taking the genetic profile into account.

• Frigaard, Julie Mari; Jensen, Janicke Liaaen; Galtung, Hilde & Hiorth, Marianne (2022). The Potential of Chitosan in Nanomedicine: An Overview of the Cytotoxicity of Chitosan Based Nanoparticles. Frontiers in Pharmacology. 13. doi: 10.3389/fphar.2022.880377. Full text in Research Archive Show summary

  The unique properties and applications of nanotechnology in targeting drug delivery, cosmetics, fabrics, water treatment and food packaging have received increased focus the last two decades. The application of nanoparticles in medicine is rapidly evolving, requiring careful investigation of toxicity before clinical use. Chitosan, a derivative of the natural polysaccharide chitin, has become increasingly relevant in modern medicine because of its unique properties as a nanoparticle. Chitosan is already widely used as a food additive and in food packaging, bandages and wound dressings. Thus, with an increasing application worldwide, cytotoxicity assessment of nanoparticles prepared from chitosan is of great interest. The purpose of this review is to provide an updated status of cytotoxicity studies scrutinizing the safety of chitosan nanoparticles used in biomedical research. A search in Ovid Medline from 23 March 1998 to 4 January 2022, with the combination of the search words Chitosan or chitosan , nanoparticle or nano particle or nanosphere or nanocapsule or nano capsule , toxicology or toxic or cytotoxic and mucosa or mucous membrane resulted in a total of 88 articles. After reviewing all the articles, those involving non-organic nanoparticles and cytotoxicity assays conducted exclusively on nanoparticles with anti-tumor effect (i.e., having cytotoxic effect) were excluded, resulting in 70 articles. Overall, the chitosan nanoparticles included in this review seem to express low cytotoxicity regardless of particle composition or cytotoxicity assay and cell line used for testing. Nonetheless, all new chitosan derivatives and compositions are recommended to undergo careful characterization and cytotoxicity assessment before being implemented on the market.

• Khatri, Bhuwan; Tessneer, Kandice L.; Rasmussen, Astrid; Aghakhanian, Farhang; Reksten, Tove Ragna & Adler, Adam [Show all 66 contributors for this article] (2022). Genome-wide association study identifies Sjögren’s risk loci with functional implications in immune and glandular cells. Nature Communications. 13(1), p. 1–17. doi: 10.1038/s41467-022-30773-y. Full text in Research Archive Show summary

  Sjögren’s disease is a complex autoimmune disease with twelve established susceptibility loci. This genome-wide association study (GWAS) identifies ten novel genome-wide significant (GWS) regions in Sjögren’s cases of European ancestry: CD247, NAB1, PTTG1-MIR146A, PRDM1-ATG5, TNFAIP3, XKR6, MAPT-CRHR1, RPTOR-CHMP6-BAIAP6, TYK2, SYNGR1. Polygenic risk scores yield predictability (AUROC = 0.71) and relative risk of 12.08. Interrogation of bioinformatics databases refine the associations, define local regulatory networks of GWS SNPs from the 95% credible set, and expand the implicated gene list to >40. Many GWS SNPs are eQTLs for genes within topologically associated domains in immune cells and/or eQTLs in the main target tissue, salivary glands.

• Hynne, Håvard; Sandås, Elise Mørk; Elgstøen, Katja B. Prestø; Rootwelt, Helge; Utheim, Tor Paaske & Galtung, Hilde [Show all 7 contributors for this article] (2022). Saliva Metabolomics in Dry Mouth Patients with Head and Neck Cancer or Sjögren’s Syndrome. Cells. 11(3). doi: 10.3390/cells11030323. Full text in Research Archive Show summary

  The etiology of dry mouth conditions is multi-faceted. Patients radiated after head and neck cancer (HNC) and those with primary Sjögren’s syndrome (pSS) share many of the same symptoms despite different causes. With the aim of better understanding the pathophysiology and biochemical processes behind dry mouth with different etiologies, we investigated the metabolic profile of 10 HNC patients, 9 pSS patients and 10 healthy controls using high-performance liquid chromatography-high resolution mass spectrometry (HPLC-MS) metabolomics. Principal component analysis (PCA) revealed different metabolic profiles when comparing all subjects included in the study. Both patient groups showed higher ratios of several pyrimidine nucleotides and nucleosides when compared to controls. This finding may indicate that purinergic signaling plays a role in dry mouth conditions. Moreover, significantly increased levels of DL-3-aminoisobutyric acid were found in HNC patients when compared to controls, and a similar tendency was observed in the pSS patients. Furthermore, a dysregulation in amino acid metabolism was observed in both patient groups. In conclusion, metabolomics analysis showed separate metabolic profiles for HNC and pSS patients as compared to controls that could be useful in diagnostics and for elucidating the different pathophysiologies. The demonstrated dysregulation of pyrimidine nucleotides and levels of metabolites derived from amino acids in the patient groups should be studied further.

• Chen, Xiangjun; Badian, Reza; Hynne, Håvard; Tashbayev, Behzod; Hove, Lene Hystad & Jensen, Janicke Liaaen [Show all 7 contributors for this article] (2022). Morphology of Meibomian Glands in A 65‐Year‐Old Norwegian Population without Dry Eye Disease. Journal of Clinical Medicine. 11(3). doi: 10.3390/jcm11030527. Full text in Research Archive Show summary

  Analyses of meibography may help in the diagnosis, prevention, and management of meibomian gland dysfunction (MGD). However, there is currently a paucity of data regarding meibography analyses in the young elderly populations in the Nordic countries. In the current study, meibography of the upper and lower eyelids of 117 65-year-old residents in Oslo, Norway, who did not fulfil the diagnosis of dry eye disease (DED) were analysed. Meibomian gland (MG) dropout and tarsal areas were measured semi-automatically using ImageJ software. The relationship between morphological features of the MGs and clinical dry eye tests was examined. The median percent MG dropout was 26.1% and 40.7% in the upper and lower eyelids, respectively. There was no significant difference between males and females. None of the MG morphological parameters demonstrated significant values in discriminating abnormal dry eye symptom loads or MGD diagnosis from the normal loads. We therefore concluded that moderate MG atrophy was common among the Norwegian population of 65-year-olds without DED and showed no sexual differences. Meibography alone cannot discriminate MGD from non-MGD; thus, both morphological and functional MG tests are necessary when screening for MGD.

• Hynne, Håvard; Aqrawi, Lara A.; Jensen, Janicke Liaaen; Thiede, Bernd; Palm, Øyvind & Amdal, Cecilie Delphin [Show all 10 contributors for this article] (2022). Proteomic Profiling of Saliva and Tears in Radiated Head and Neck Cancer Patients as Compared to Primary Sjögren’s Syndrome Patients. International Journal of Molecular Sciences. ISSN 1661-6596. 23(7). doi: 10.3390/ijms23073714. Full text in Research Archive Show summary

  Patients with head and neck cancer (HNC) and patients with primary Sjögren’s syndrome (pSS) may exhibit similar symptoms of dry mouth and dry eyes, as a result of radiotherapy (RT) or a consequence of disease progression. To identify the proteins that may serve as promising disease biomarkers, we analysed saliva and tears from 29 radiated HNC patients and 21 healthy controls, and saliva from 14 pSS patients by mass spectrometry-based proteomics. The study revealed several upregulated, and in some instances overlapping, proteins in the two patient groups. Histone H1.4 and neutrophil collagenase were upregulated in whole saliva of both patient groups, while caspase-14, histone H4, and protein S100-A9 were upregulated in HNC saliva only. In HCN tear fluid, the most highly upregulated protein was mucin-like protein 1. These overexpressed proteins in saliva and tears play central roles in inflammation, host cell injury, activation of reactive oxygen species, and tissue repair. In conclusion, the similarities and differences in overexpressed proteins detected in saliva from HNC and pSS patients may contribute to the overall understanding of the different pathophysiological mechanisms inducing dry mouth. Thus, the recurring proteins identified could possibly serve as future promising biomarkers

• Diep, My Tien; Jensen, Janicke Liaaen; Skudutyte-Rysstad, Rasa; Young, Alix; Sødal, Anne Thea Tveit & Petrovski, Beata [Show all 7 contributors for this article] (2021). Xerostomia and hyposalivation among a 65-yr-old population living in Oslo, Norway. European Journal of Oral Sciences. ISSN 0909-8836. 129(1), p. 1–11. doi: 10.1111/eos.12757. Full text in Research Archive Show summary

  This study aimed to describe the prevalence and associated factors for xerostomia and hyposalivation in a young-elderly population. A random sample of 460 65-yr-old people living in Oslo, Norway, answered a questionnaire and underwent a clinical examination (237 men and 223 women; response rate 58%). Ten percent of respondents reported xerostomia. The median Summated Xerostomia Index was 6 (interquartile range [IQR]: 5–7) and the median Clinical Oral Dryness Score was 2 (IQR: 1–3). The median unstimulated whole saliva (UWS) secretion rate was 0.34 (IQR: 0.20–0.53) mL min–1 and the median stimulated whole saliva (SWS) secretion rate was 1.74 (IQR: 1.24–2.38) mL min–1. In 8% of the study participants the UWS secretion rate was ≤0.1 mL min–1 and in 4% the SWS secretion rate was ≤0.7 mL min–1. Three percent of the study participants had both xerostomia and hyposalivation with respect to UWS. Xerostomia was significantly associated with medication use, having rheumatic disease, and having received radiation therapy to the head/neck region. Hyposalivation with respect to UWS and SWS was significantly associated with medication use and type II diabetes. Even though xerostomia and hyposalivation were not prevalent conditions in this population, clinicians should be especially aware of the salivary conditions in patients taking four or more medications, patients diagnosed with type II diabetes, and those who have undergone radiation therapy to the head/neck region.

• Fineide, Fredrik; Chen, Xiangjun; Bjellaas, Thomas; Vitelli, Valeria; Utheim, Tor Paaske & Jensen, Janicke Liaaen [Show all 7 contributors for this article] (2021). Characterization of lipids in saliva, tears and minor salivary glands of sjögren’s syndrome patients using an hplc/ms‐based approach. International Journal of Molecular Sciences. ISSN 1661-6596. 22(16). doi: 10.3390/ijms22168997. Full text in Research Archive Show summary

  The diagnostic work-up of primary Sjögren’s syndrome (pSS) includes quantifying saliva and tear production, evaluation of autoantibodies in serum and histopathological analysis of minor salivary glands. Thus, the potential for further utilizing these fluids and tissues in the quest to find better diagnostic and therapeutic tools should be fully explored. Ten samples of saliva and tears from female patients diagnosed with pSS and ten samples of saliva and tears from healthy females were included for lipidomic analysis of tears and whole saliva using high-performance liquid chromatography coupled to time-of-flight mass spectrometry. In addition, lipidomic analysis was performed on minor salivary gland biopsies from three pSS and three non-SS females. We found significant differences in the lipidomic profiles of saliva and tears in pSS patients compared to healthy controls. Moreover, there were differences in individual lipid species in stimulated saliva that were comparable to those of glandular biopsies, representing an intriguing avenue for further research. We believe a comprehensive elucidation of the changes in lipid composition in saliva, tears and minor salivary glands in pSS patients may be the key to detecting pSS-related dry mouth and dry eyes at an early stage. The identified differences may illuminate the path towards future innovative diagnostic methodologies and treatment modalities for alleviating pSS-related sicca symptoms.

• Samuelsen, Tea Marie B; Aqrawi, Lara A.; Skarstein, Kathrine & Jensen, Janicke Liaaen (2021). Evaluering av spyttkjertelbiopsier ved utredning av Sjögrens syndrom. Den norske tannlegeforenings Tidende. ISSN 0029-2303. 131, p. 988–994. Full text in Research Archive
• Matri, Kristine Lindstad & Jensen, Janicke Liaaen (2021). Kirurgisk behandling av retinert andre molar i underkjeven. En retrospektiv studie. Den norske tannlegeforenings Tidende. ISSN 0029-2303. 131, p. 358–366. Full text in Research Archive
• Westgaard, Kristine Løken; Hynne, Håvard; Amdal, Cecilie Delphin; Young, Alix; Singh, Preet Bano & Chen, Xiangjun [Show all 12 contributors for this article] (2021). Oral and ocular late effects in head and neck cancer patients treated with radiotherapy. Scientific Reports. 11:4026, p. 1–11. doi: 10.1038/s41598-021-83635-w. Full text in Research Archive Show summary

  A broader understanding of oral and ocular late effects in head and neck cancer (HNC) patients who underwent intensity-modulated radiotherapy (IMRT) may provide valuable information in follow-up and improve quality of life. Twenty-nine HNC patients treated at least 6 months earlier and 30 age-matched controls were recruited. After completing several questionnaires: Oral Health Impact Profile-14 (OHIP-14), Shortened Xerostomia Inventory (SXI), Ocular Surface Disease Index (OSDI) and McMonnies Dry Eye questionnaire (MDEQ), participants underwent oral and ocular examinations. Oral examination included clinical oral dryness score (CODS) and secretion rates of unstimulated and stimulated saliva (UWS, SWS). Ocular examination included tear film break-up time, Schirmer test and ocular surface staining. The patients had more problems related to dry mouth than controls based on CODS and SXI, and more complaints of dry eye disease based on OSDI and MDEQ. UWS and SWS rates and oral health related quality of life were significantly lower in the patient group. Subjective oral dryness (SXI) correlated significantly with subjective ocular dryness (OSDI and MDEQ). Our study demonstrates that HNC patients treated with IMRT experience late effects in terms of xerostomia and ocular dryness underlining the importance of interdisciplinary approach in the evaluation and follow-up of HNC patients.

• Chen, Xiangjun; Badian, Reza; Hynne, Håvard; Amdal, Cecilie Delphin; Herlofson, Bente Brokstad & Utheim, Øygunn Aass [Show all 10 contributors for this article] (2021). Alterations in meibomian glands in patients treated with intensity-modulated radiotherapy for head and neck cancer. Scientific Reports. 11:22419, p. 1–7. doi: 10.1038/s41598-021-01844-9. Full text in Research Archive Show summary

  Patients undergoing intensity-modulated radiotherapy (IMRT) for head and neck cancer may have increased incidence of dry eye disease and the exact mechanism is unclear. The present study aims to assess tear film and meibomian gland (MG) features in patients who received IMRT for head and neck cancer not involving the orbital area. Twenty-seven patients (64.7 ± 9.8 years) and 30 age-matched controls (61.4 ± 11.0 years) underwent a comprehensive dry eye work-up. Compared to the control group, the patients had more lid margin abnormalities, and worse meibum quality. The MG loss, calculated as (tarsal area-MG area)/tarsal area, was higher in the patient group in both the upper (53.0 ± 12.0% vs. 35.1 ± 10.3%, p < 0.001) and lower lids (69.5 ± 12.6% vs. 48.5 ± 12.5%, p < 0.001). In the patient group, more MG loss in the lower lids correlated with worse meibum quality (r = 0.445, p = 0.029). In contrast, there was no significant difference in aqueous tear production level, measured with Schirmer test. Patients treated with IMRT for head and neck cancer seemed to have comparable lacrimal gland function to the controls despite more dry eye symptoms. However, the patients had MG functional and morphological changes, which may present a higher risk for developing dry eye disease.

• Cruz, Ariana Dela; Kartha, Vinay; Tilston-Lunel, Andrew; Mi, Rongjuan; Reynolds, Taylor L. & Mingueneau, Michael [Show all 11 contributors for this article] (2021). Gene expression alterations in salivary gland epithelia of Sjögren’s syndrome patients are associated with clinical and histopathological manifestations. Scientific Reports. 11, p. 1–12. doi: 10.1038/s41598-021-90569-w. Full text in Research Archive Show summary

  Sjögren’s syndrome (SS) is a complex autoimmune disease associated with lymphocytic infiltration and secretory dysfunction of salivary and lacrimal glands. Although the etiology of SS remains unclear, evidence suggests that epithelial damage of the glands elicits immune and fibrotic responses in SS. To define molecular changes underlying epithelial tissue damage in SS, we laser capture microdissected (LCM) labial salivary gland epithelia from 8 SS and 8 non-SS controls for analysis by RNA sequencing (RNAseq). Computational interrogation of gene expression signatures revealed that, in addition to a division of SS and non-SS samples, there was a potential intermediate state overlapping clustering of SS and non-SS samples. Differential expression analysis uncovered signaling events likely associated with distinct SS pathogenesis. Notable signals included the enrichment of IFN-γ and JAK/STAT-regulated genes, and the induction of genes encoding secreted factors, such as LTF, BMP3, and MMP7, implicated in immune responses, matrix remodeling and tissue destruction. Identification of gene expression signatures of salivary epithelia associated with mixed clinical and histopathological characteristics suggests that SS pathology may be defined by distinct molecular subtypes. We conclude that gene expression changes arising in the damaged salivary epithelia may offer novel insights into the signals contributing to SS development and progression.

• Aqrawi, Lara A.; Chen, Xiangjun; Hynne, Håvard; Amdal, Cecilie Delphin; Reppe, Sjur & Aass, Hans Christian Dalsbotten [Show all 14 contributors for this article] (2020). Cytokines Explored in Saliva and Tears from Radiated Cancer Patients Correlate with Clinical Manifestations, Influencing Important Immunoregulatory Cellular Pathways. Cells. 9(9). doi: 10.3390/cells9092050. Full text in Research Archive Show summary

  Although radiotherapy is a common form of treatment for head and neck cancer, it may lead to tissue damage in the salivary and lacrimal glands, possibly affecting cytokine expression in the gland fluid of treated individuals. Cytokine profiles in saliva and tear fluid of 29 radiated head and neck cancer patients and 20 controls were screened using a multiplex assay. Correlations between cytokine expression and clinical oral and ocular manifestations were examined, and cellular pathways influenced by these cytokines were assessed using the Functional Enrichment Analysis Tool. Significantly elevated cytokines identified in patient saliva were CCL21, IL-4, CX3CL1, CCL2, CXCL1 and CCL15. Many of these cytokines correlated positively with objective signs of oral dryness, and reduced saliva production in the patients. Although CCL21 and IL-4 levels were significantly lower in patient tear fluid, they correlated with subjective ocular symptoms. These increased salivary cytokines affected pro-inflammatory and apoptotic cellular pathways, including T cell signalling, several interleukin signalling pathways, TNF and TGF-β receptor signalling, and the apoptotic p53 pathway. In conclusion, the upregulated salivary cytokines identified suggest an interplay between innate and adaptive immunity, affecting immunoregulatory cellular pathways. Whether this is due to late effects of radiotherapy or tissue repair remains to be investigated.

• Øyri, Hauk Furnes; Jensen, Janicke Liaaen; Barkvoll, Pål; Jonsdottir, Olga Hrønn; Reseland, Janne Elin & Bjørnland, Tore (2020). Incidence of alveolar osteitis after mandibular third molar surgery. Can inflammatory cytokines be identified locally? Acta Odontologica Scandinavica. ISSN 0001-6357. 79(3), p. 205–211. doi: 10.1080/00016357.2020.1817546. Full text in Research Archive Show summary

  Objectives The aims of the present study were to evaluate the relative incidence of alveolar osteitis (AO) after mandibular third molar surgery, post-operative findings and local expression of bone markers and cytokines. Study design In 445 patients, unilateral surgical third molars extractions were undertaken (584 teeth). Bone markers and cytokines were explored at the AO side and on the un-operated contralateral side and compared with the levels in samples from a control group of 18 persons without AO. Results The relative incidence of AO was 4.6%. Patients (n = 27) with AO were invited to participate in the study and 21 (77.8%) did so. Patients with AO had 1–4 extra visits for treatment of AO, the mean follow-up time was 2.6 days for all patients. There were significantly higher levels of bone markers and cytokines in the AO site compared with the un-operated contralateral site, except for Epidermal growth factor (EGF). No significant difference in expression of bone markers and cytokines between the AO and control groups was found. Lower maximum inter-incisor opening (MIO) was correlated with increased Macrophage inflammatory protein 1 alpha. A negative correlation between patients’ complaint of trismus and MIO was seen. Conclusions The relative incidence of AO was low in our patient group treated with surgical removal of third molars. AO was more frequently seen in female patients. Treatment of AO required up to four extra visits. The study provides some information on the role of cytokines in AO; but further studies are required.

• Tashbayev, Behzod; Garen, Torhild Oddveig; Palm, Øyvind; Chen, Xiangjun; Herlofson, Bente Brokstad & Vik, Alix Rosslyn Young [Show all 13 contributors for this article] (2020). Patients with non-Sjögren's sicca report poorer general and oral health-related quality of life than patients with Sjögren's syndrome: a cross-sectional study. Scientific Reports. 10(2063). doi: 10.1038/s41598-020-59078-0. Full text in Research Archive Show summary

  Understanding the impact of the disease on quality of life is crucial in patient management. In this cross-sectional study, general and oral health-related quality of life questionnaires, and thorough examinations of oral and ocular dryness were performed in age- and sex-matched patients with primary Sjögren’s syndrome (pSS group), non-Sjögren’s syndrome sicca (non-SS group) and healthy controls. General and oral health-related quality of life were investigated with the 36-Item Short Form Health Survey and the 14-Item Oral Health Impact Profle questionnaires, respectively. Subjective symptoms of xerostomia and ocular dryness were recorded using the Summated Xerostomia Inventory and Ocular Surface Disease Index, respectively. Clinical examinations included evaluation of clinical oral dryness scores, candida counts, unstimulated and stimulated saliva secretory rates, tear osmolarity, tear flm break-up time, Schirmer I test and ocular surface staining. Both patient groups had pronounced signs and symptoms of xerostomia and ocular dryness. Even though the non-SS patients had less severe clinical signs than the pSS patients, they demonstrated much poorer general and oral health-related quality of life. In conclusion, non-SS patients require more attention in order to improve their quality of life.

• Tashbayev, Behzod; Utheim, Tor Paaske; Utheim, Øygunn Aass; Ræder, Sten; Jensen, Janicke Cecilie Liaaen & Yazdani, Mazyar [Show all 10 contributors for this article] (2020). Utility of Tear Osmolarity Measurement in Diagnosis of Dry Eye Disease. Scientific Reports. 10, p. 1–7. doi: 10.1038/s41598-020-62583-x. Full text in Research Archive Show summary

  The prevalence of dry eye disease is high worldwide and poses a great burden on patients’ daily lives. Accurate diagnosis of the disease is important, and it requires application of various methods. Hyperosmolarity is believed to be the disease marker and thus measuring it provides useful information. In this study we investigated utility of tear osmolarity measured with TearLab osmometer, along with other diagnostic tests (Ocular Surface Disease Index questionnaire, Tear flm break-up time, Ocular Protection Index, Ocular Surface Staining, Schirmer I test, Meibomian gland functionality in 757 patients (1514 eyes) with dry eye disease and 29 healthy controls (58 eyes). Statistical diferences between the patient group and the control group were observed for all the tests apart from tear osmolarity, regardless of cut-of value (>308mOsm/L, >316mOsm/L, and inter-eye diference >8mOsm/L). Moreover, in the receiver operating characteristics curve analyses tear osmolarity measurement could not discriminate dry eye disease pathological scores. Therefore, our study suggests that tear osmolarity measured with TearLab osmometer cannot be used as a key indicator of DED.

• Aqrawi, Lara Adnan; Jensen, Janicke Cecilie Liaaen; Fromreide, Siren; Galtung, Hilde Kanli & Skarstein, Kathrine (2020). Expression of NGAL-specific cells and mRNA levels correlate with inflammation in the salivary gland, and its overexpression in the saliva, of patients with primary Sjögren’s syndrome. Autoimmunity. ISSN 0891-6934. 53(6), p. 1–11. doi: 10.1080/08916934.2020.1795140. Full text in Research Archive Show summary

  Salivary gland involvement is a characteristic feature of primary Sjögren’s syndrome (pSS), where tissue destruction is mediated by infiltrating immune cells, and may be accompanied by the presence of adipose tissue. Optimally diagnosing this multifactorial disease requires the incorporation of additional routines. Screening for disease-specific biomarkers in biological fluid could be a promising approach to increase diagnostic accuracy. We have previously investigated disease biomarkers in saliva and tear fluid of pSS patients, identifying Neutrophil gelatinase-associated lipocalin (NGAL) as the most upregulated protein in pSS. In the current study, we aimed to explore for the first time NGAL expression at the site of inflammation in the pSS disease target organ. Immunohistochemical staining was conducted on minor salivary gland biopsies from 11 pSS patients and 11 non-SS sicca subjects, targeting NGAL-specific cells. Additional NGAL/PNAd double staining was performed to study NGAL expression in high endothelial venules, known as specialised vascular structures. Moreover, NGAL mRNA expression was measured utilising quantitative real-time polymerase chain reaction (qRT-PCR) on minor salivary gland biopsies from 15 pSS patients and 7 non-SS sicca individuals that served as tissue controls. Our results demonstrated NGAL expression in acinar and ductal epithelium within the salivary gland of pSS patients, where significantly greater levels of acinar NGAL were observed in pSS patients (p < .0018) when compared to non-SS subjects. Also, acinar expression positively correlated with focus score values (r 2 = 0.54, p < .02), while ductal epithelial expression showed a negative such correlation (r 2 = 0.74, p < .003). Some PNAD+ endothelial venules also expressed NGAL. An increase in NGAL staining with increased fatty replacement was also observed in pSS patients. Concurringly, a 27% increase in NGAL mRNA levels were also detected in the minor salivary glands of pSS patients when compared to non-SS tissue control subjects. In conclusion, there is a positive association between increase in NGAL expression and inflammation in the pSS disease target organ, which also coincides with its previously demonstrated upregulation in the saliva of pSS patients. Additional functional analyses are needed to better understand the immunological implications of this potential biomarker.

• Thorlacius, Gudny Ella; Hultin-Rosenberg, Lina; Sandling, Johanna K.; Bianchi, Matteo; Imgenberg-Kreuz, Juliana & Pucholt, Pascal [Show all 32 contributors for this article] (2020). Genetic and clinical basis for two distinct subtypes of primary Sjögren's syndrome. Rheumatology. ISSN 1462-0324. 60(2), p. 837–848. doi: 10.1093/rheumatology/keaa367. Full text in Research Archive Show summary

  Objectives Clinical presentation of primary Sjögren’s syndrome (pSS) varies considerably. A shortage of evidence-based objective markers hinders efficient drug development and most clinical trials have failed to reach primary endpoints. Methods We performed a multicentre study to identify patient subgroups based on clinical, immunological and genetic features. Targeted DNA sequencing of 1853 autoimmune-related loci was performed. After quality control, 918 patients with pSS, 1264 controls and 107 045 single nucleotide variants remained for analysis. Replication was performed in 177 patients with pSS and 7672 controls. Results We found strong signals of association with pSS in the HLA region. Principal component analysis of clinical data distinguished two patient subgroups defined by the presence of SSA/SSB antibodies. We observed an unprecedented high risk of pSS for an association in the HLA-DQA1 locus of odds ratio 6.10 (95% CI: 4.93, 7.54, P=2.2×10−62) in the SSA/SSB-positive subgroup, while absent in the antibody negative group. Three independent signals within the MHC were observed. The two most significant variants in MHC class I and II respectively, identified patients with a higher risk of hypergammaglobulinaemia, leukopenia, anaemia, purpura, major salivary gland swelling and lymphadenopathy. Replication confirmed the association with both MHC class I and II signals confined to SSA/SSB antibody positive pSS. Conclusion Two subgroups of patients with pSS with distinct clinical manifestations can be defined by the presence or absence of SSA/SSB antibodies and genetic markers in the HLA locus. These subgroups should be considered in clinical follow-up, drug development and trial outcomes, for the benefit of both subgroups.

• Khalafalla, Mahmoud G.; Woods, Lucas T.; Jasmer, Kimberly J.; Forti, Kevin Munoz; Camden, Jean M. & Jensen, Janicke Liaaen [Show all 9 contributors for this article] (2020). P2 receptors as therapeutic targets in the salivary gland: From physiology to dysfunction. Frontiers in Pharmacology. 11:222, p. 1–223. doi: 10.3389/fphar.2020.00222. Full text in Research Archive Show summary

  Although often overlooked in our daily lives, saliva performs a host of necessary physiological functions, including lubricating and protecting the oral cavity, facilitating taste sensation and digestion and maintaining tooth enamel. Therefore, salivary gland dysfunction and hyposalivation, often resulting from pathogenesis of the autoimmune disease Sjögren’s syndrome or from radiotherapy of the head and neck region during cancer treatment, severely reduce the quality of life of afflicted patients and can lead to dental caries, periodontitis, digestive disorders, loss of taste and difficulty speaking. Since their initial discovery in the 1970s, P2 purinergic receptors for extracellular nucleotides, including ATP-gated ion channel P2X and G protein-coupled P2Y receptors, have been shown to mediate physiological processes in numerous tissues, including the salivary glands where P2 receptors represent a link between canonical and non-canonical saliva secretion. Additionally, extracellular nucleotides released during periods of cellular stress and inflammation act as a tissue alarmin to coordinate immunological and tissue repair responses through P2 receptor activation. Accordingly, P2 receptors have gained widespread clinical interest with agonists and antagonists either currently undergoing clinical trials or already approved for human use. Here, we review the contributions of P2 receptors to salivary gland function and describe their role in salivary gland dysfunction. We further consider their potential as therapeutic targets to promote physiological saliva flow, prevent salivary gland inflammation and enhance tissue regeneration.

• Aqrawi, Lara Adnan; Galtung, Hilde; Guerreiro, Eduarda; Øvstebø, Reidun; Thiede, Bernd & Utheim, Tor Paaske [Show all 11 contributors for this article] (2019). Proteomic and histopathological characterisation of sicca subjects and primary Sjögren’s syndrome patients reveals promising tear, saliva and extracellular vesicle disease biomarkers. Arthritis Research & Therapy. ISSN 1478-6354. 21, p. 1–14. doi: 10.1186/s13075-019-1961-4. Full text in Research Archive Show summary

  Background Mononuclear cell infiltration of exocrine glands, production of Ro/SSA and La/SSB autoantibodies, along with oral and ocular dryness, are characteristic features of primary Sjögren’s syndrome (pSS). Non-SS sicca subjects, an underexplored group in relation to pSS, display similar sicca symptoms, with possible mild signs of inflammation in their salivary glands, yet with no serological detection of autoantibody production. In this study, we investigated inflammatory manifestations in the salivary gland tissue, tear fluid and saliva of non-SS subjects, as compared to pSS patients and healthy individuals. Methods Fifteen non-SS, 10 pSS and 10 healthy subjects were included in the analyses. Histological evaluation of salivary gland biopsies was performed. Liquid chromatography-mass spectrometry (LC-MS) was conducted on tear fluid and stimulated whole saliva, and proteomic biomarker profiles were generated. Extracellular vesicle (EVs) isolation and characterisation from both fluids were also combined with LC-MS. The LC-MS data were analysed for quantitative differences between patient and control groups using Scaffold. Database for Annotation, Visualization and Integrated Discovery (DAVID) and Functional Enrichment Analysis Tool (FunRich) were applied for functional analyses. Results Histopathological evaluation of salivary gland biopsies showed implications of milder inflammation in non-SS subjects through mononuclear cell infiltration, fibrosis and fatty replacement, as compared to pSS patients. Although unaffected in the non-SS group, upregulation of proinflammatory pathways and proteins involved in ubiquitination (LMO7 and HUWE1) and B cell differentiation (TPD52) were detected in tear fluid of pSS patients. Moreover, overexpression of proteins STOM, ANXA4 and ANXA1, regulating cellular innate and adaptive immunological pathways, were further identified in EVs from tear fluid of pSS patients. Finally, whole saliva and EVs isolated from whole saliva of pSS patients expressed proteins vital for innate MHC class I cellular regulation (NGAL) and T cell activation (CD44). Conclusions Non-SS sicca subjects may show implications of mild inflammation in their glandular tissue, while their protein profile was strikingly more similar to healthy controls than to pSS patients. Hence, the tear and salivary biomarkers identified could be implemented as potential non-invasive diagnostic tools that may aid in increasing diagnostic accuracy when evaluating non-SS subjects and pSS patients and monitoring disease progression.

• Saltnes, Solfrid Sørgjerd; Geirdal, Amy Østertun; Sæves, Rønnaug Ingun; Jensen, Janicke Liaaen & Nordgarden, Hilde (2019). Experiences of daily life and oral rehabilitation in oligodontia - a qualitative study. Acta Odontologica Scandinavica. ISSN 0001-6357. doi: 10.1080/00016357.2018.1535137. Full text in Research Archive Show summary

  Objective: Quantitative research indicate increased anxiety and poorer mental health related quality of life (QoL) in individuals with oligodontia (congenitally absence of six or more teeth). The aim of this qualitative study was to complement and explore the individuals’ experiences of life and oral rehabilitation, hopefully improving the care for these patients. Material and methods: Twelve participants (6 females, 6 males, aged 21-48) with oligodontia and experiences of comprehensive dental treatments, consented to participate in a semi-structured interview. The questions in the interview guide were based on previous research and clinical experience and included both open (i.e. how is your life?) and specific questions (i.e. do health care personnel know enough about your condition?). The interview transcripts were coded and analysed using a phenomenological method of analysis. The Regional Ethics Committee approved the study. Results: The following themes grew out of the data; “feeling of being different”, “the burden of treatment”, “shared decision-making”, “treatment increases self-esteem” and “use of coping strategies”. Psychological distress and reduced QoL seemed to be related to negative aspects of the themes, which covered unacceptable aesthetics, reduced orofacial function, the long-term process of oral rehabilitation, and negative experiences with healthcare services. The informants used problem focused and emotionally focused strategies to meet these challenges. Finalizing oral rehabilitation and shared decision making were positive aspects of the themes. Conclusion: All themes expressed by the participants were of importance for experienced QoL and psychological distress, and should be acknowledged by health care personnel when planning and performing treatment.

• Skarstein, Kathrine; Jensen, Janicke Liaaen; Galtung, Hilde; Jonsson, Roland; Brokstad, Karl Albert & Aqrawi, Lara A. (2019). Autoantigen-specific B cells and plasma cells are prominent in areas of fatty infiltration in salivary glands of patients with primary Sjogren?s syndrome. Autoimmunity. ISSN 0891-6934. 52, p. 242–250. doi: 10.1080/08916934.2019.1684475. Full text in Research Archive
• Rusthen, Shermin; Kristoffersen, Anne Karin; Young, Alix; Galtung, Hilde; Petrovski, Beata & Palm, Øyvind [Show all 8 contributors for this article] (2019). Dysbiotic salivary microbiota in dry mouth and primary Sjögren’s syndrome patients. PLOS ONE. 14(6), p. 1–15. doi: 10.1371/journal.pone.0218319. Full text in Research Archive Show summary

  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.

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• Hynne, Håvard; Frigaard, Julie Mari & Jensen, Janicke Liaaen (2024). Dry mouth severity score. Full text in Research Archive
• Frigaard, Julie Mari; Galtung, Hilde & Jensen, Janicke Liaaen (2024). Use and simplification of the Dry Mouth Severity Score. Full text in Research Archive
• Ringstad, Ingrid Beate; Romskaug, Rita; Fjeld, Katrine Gahre; Hove, Lene Hystad; Santervas, Leonor Roa & Wyller, Torgeir Bruun [Show all 7 contributors for this article] (2024). Exploring Associations Between Medication Use, Frailty and Oral Health in Acutely Ill Older Adults. Full text in Research Archive
• Ringstad, Ingrid Beate; Romskaug, Rita; Fjeld, Katrine Gahre; Hove, Lene Hystad; Santervas, Leonor Roa & Wyller, Torgeir Bruun [Show all 7 contributors for this article] (2024). Dry Mouth, Frailty and Polypharmacy in Acutely Ill Older Adults. Full text in Research Archive
• Jensen, Janicke Liaaen (2024). Min forskning på Sjøgrens syndrom med mer. Full text in Research Archive
• Ringstad, Ingrid Beate; Romskaug, Rita; Fjeld, Katrine Gahre; Hove, Lene Hystad; Santervas, Leonor Roa & Wyller, Torgeir Bruun [Show all 7 contributors for this article] (2024). Preliminary data from the COOP II study - exploring oral and general health among older people in need of acute care. Full text in Research Archive
• Ringstad, Ingrid Beate; Romskaug, Rita; Fjeld, Katrine Gahre; Hove, Lene Hystad; Santervas, Leonor Roa & Wyller, Torgeir Bruun [Show all 7 contributors for this article] (2024). Preliminary data from the COOP II study – exploring oral and general health among older people in need of short-time acute care. Full text in Research Archive
• Santervas, Leonor Roa; Wyller, Torgeir Bruun; Skovlund, Eva; Kristoffersen, Espen Saxhaug; Ringstad, Ingrid Beate & Jensen, Janicke Cecilie Liaaen [Show all 9 contributors for this article] (2024). Frailty and Health-Related Quality of Life in Older Adults Admitted to Oslo Municipal In-Patient Acute Care Unit. Full text in Research Archive
• Rogn, Åsmund; Jensen, Janicke Liaaen; Iversen, Per Ole & Singh, Preet Bano (2024). Correction to: Post-COVID-19 patients suffer from chemosensory, trigeminal, and salivary dysfunctions (Scientific Reports, (2024), 14, 1, (3455), 10.1038/s41598-024-53919-y). Scientific Reports. 14(1). doi: 10.1038/s41598-024-59915-6. Full text in Research Archive
• Santervas, Leonor Roa; Wyller, Torgeir Bruun; Skovlund, Eva; Jensen, Janicke Liaaen; Fjeld, Katrine Gahre & Hove, Lene Hystad [Show all 11 contributors for this article] (2024). Cooperation across healthcare service levels for medication reviews in older people with polypharmacy admitted to a municipal in-patient acute care unit (The COOP II Study): study protocol for a randomized controlled trial. Trials. 25(1). doi: 10.1186/s13063-024-08442-w. Full text in Research Archive Show summary

  Background: Polypharmacy and inappropriate drug use are associated with adverse health outcomes in older people. Collaborative interventions between geriatricians and general practitioners have demonstrated effectiveness in improving clinical outcomes for complex medication regimens in home-dwelling patients. Since 2012, Norwegian municipalities have established municipal in-patient acute care (MipAC) units, designed to contribute towards reducing the number of hospital admissions. These units predominantly serve older people who typically benefit from multidisciplinary approaches. The primary objective of this study is to evaluate the effect of cooperative medication reviews conducted by MipAC physicians, supervised by geriatricians, and in collaboration with general practitioners, on health-related quality of life and clinical outcomes in MipAC patients ≥ 70 years with polypharmacy. Additionally, the study aims to assess the carbon footprint of the intervention. Methods: This is a randomized, single-blind, controlled superiority trial with 16 weeks follow-up. Participants will be randomly assigned to either the control group, receiving usual care at the MipAC unit, or to the intervention group which in addition receive clinical medication reviews that go beyond what is considered usual care. The medication reviews will evaluate medication appropriateness using a structured but individualized framework, and the physicians will receive supervision from geriatricians. Following the clinical medication reviews, the MipAC physicians will arrange telephone meetings with the participants’ general practitioners to combine their assessments in a joint medication review. The primary outcome is health-related quality of life as measured by the 15D instrument. Secondary outcomes include physical and cognitive functioning, oral health, falls, admissions to healthcare facilities, and mortality. Discussion: This study aims to identify potential clinical benefits of collaborative, clinical medication reviews within community-level MipAC units for older patients with polypharmacy. The results may offer valuable insights into optimizing patient care in comparable municipal healthcare settings. Trial registration: The study was registered prospectively on ClinicalTrials.gov 30.08.2023 with identifier NCT06020391.

• Ringstad, Ingrid Beate; Borge, Hanne; Fromreide, Siren; Galtung, Hilde; Jensen, Janicke Cecilie Liaaen & Skarstein, Kathrine (2024). Investigating MMP7, MMP9 and TIMP1 mRNA expression patterns in minor salivary glands from patients with primary Sjögren’s syndrome (pSS) using RNAscope®. Full text in Research Archive
• Ringstad, Ingrid Beate; Borge, Hanne; Fromreide, Siren; Galtung, Hilde; Jensen, Janicke Cecilie Liaaen & Skarstein, Kathrine (2024). Undersøkelse av mRNA-uttrykksmønstre for MMP7, MMP9 og TIMP1 i små spyttkjertler hos pasienter med primær Sjögrens syndrom (pSS) ved bruk av RNAscope®. Full text in Research Archive
• Frigaard, Julie Mari; Jensen, Janicke Liaaen & Hynne, Håvard (2023). Development of a novel scoring system to classify dry mouth severity. Full text in Research Archive
• Jensen, Janicke Liaaen & Wyller, Torgeir Bruun (2023). Den multimedisinerte pasienten. Full text in Research Archive
• Ringstad, Ingrid Beate; Romskaug, Rita; Fjeld, Katrine Gahre; Hove, Lene Hystad; Santervas, Leonor Roa & Wyller, Torgeir Bruun [Show all 7 contributors for this article] (2023). What happens to oral health when multimorbidity, polypharmacy and frailty comes along? Full text in Research Archive
• Ringstad, Ingrid Beate; Borge, Hanne; Fromreide, Siren; Galtung, Hilde; Skarstein, Kathrine & Jensen, Janicke Cecilie Liaaen (2023). Increased Expression of Salivary Gland Chemokines in Primary Sjögren’s Syndrome. Full text in Research Archive
• Ringstad, Ingrid Beate; Romskaug, Rita; Fjeld, Katrine Gahre; Hove, Lene Hystad; Santervas, Leonor Roa & Wyller, Torgeir Bruun [Show all 7 contributors for this article] (2023). Oral Health in Times of Frailty and Polypharmacy. Full text in Research Archive
• Rogn, Åsmund; Jensen, Janicke Cecilie Liaaen & Singh, Preet Bano (2023). Compromised chemosensory, trigeminal and salivary function in Long-COVID patients. Full text in Research Archive
• Khatri, Bhuwan; Tessneer, Kandice L.; Rasmussen, Astrid; Aghakhanian, Farhang; Reksten, Tove Ragna & Adler, Adam [Show all 66 contributors for this article] (2023). Author Correction: Genome-wide association study identifies Sjögren’s risk loci with functional implications in immune and glandular cells (Nature Communications, (2022), 13, 1, (4287), 10.1038/s41467-022-30773-y). Nature Communications. 14(1). doi: 10.1038/s41467-023-36369-4. Full text in Research Archive
• Lofthus, Elisabeth & Jensen, Janicke Liaaen (2023). Ny Sjøgrens-medisin: - Lovende! [Journal]. Dagbladet +. Full text in Research Archive
• Steien, Tore Rasmussen & Jensen, Janicke Liaaen (2023). Munntørrhet skyldes nesten alltid legemidler. [Journal]. Farmatid.no. Full text in Research Archive
• Jensen, Janicke Liaaen (2023). The aging mouth. Full text in Research Archive
• Singh, Preet Bano; Rogn, Åsmund & Jensen, Janicke Cecilie Liaaen (2023). Management of chemosensory, trigeminal and salivary dysfunction in Long-COVID patients. Full text in Research Archive
• Frigaard, Julie Mari; Hynne, Håvard; Randsborg, Karoline; Mellin-Olsen, Tonje; Young, Alix & Rykke, Morten [Show all 10 contributors for this article] (2022). Oral health indicators, oral health-related quality of life and nutritional aspects in medicated patients suffering from anxiety, psychosis, and/or depression. Frontiers in Public Health. Full text in Research Archive
• Jensen, Janicke Liaaen (2022). Dry mouth and oral health-related quality of life in various conditions including EDs. Full text in Research Archive
• Jensen, Janicke Liaaen (2022). Interprofessional collaboration on integrating oral and general health for the elderly in various care settings. Full text in Research Archive
• Jensen, Janicke Liaaen (2022). Tann- og munnhelsens betydning for eldres ernæring. Full text in Research Archive
• Frigaard, Julie Mari; Hynne, Håvard; Young, Alix; Hove, Lene Hystad; Rykke, Morten & Singh, Preet Bano [Show all 7 contributors for this article] (2022). Do medicated psychiatric patients differ from other dry mouth patients? Full text in Research Archive
• Jensen, Janicke Liaaen (2022). MN102 Munn- og tannsykdommer. Full text in Research Archive
• Jensen, Janicke Liaaen (2022). The aging mouth. Full text in Research Archive
• Jensen, Janicke Liaaen (2022). Kommentar til: Munnhelse i sykehjem – en undersøkelse gjort i Akershus. NTFs Tidende. 132(4), p. 666–667. Full text in Research Archive
• Khatri, Bhuwan; Tessneer, Kandice L.; Rasmussen, Astrid; Aghakhanian, Farhang; Reksten, Tove Ragna & Adler, Adam [Show all 66 contributors for this article] (2022). Erratum: Author Correction: Genome-wide association study identifies Sjögren's risk loci with functional implications in immune and glandular cells (Nature communications (2022) 13 1 (4287)). Nature Communications. 13(1), p. 6519–6519. doi: 10.1038/s41467-022-34311-8. Full text in Research Archive
• Jensen, Janicke Liaaen (2021). Min Forskning: Fra lab til pasient til samfunnet. Full text in Research Archive
• Jensen, Janicke Liaaen (2021). The Dry Mouth Clinic – what is it all about? Full text in Research Archive
• Frigaard, Julie Mari; Jensen, Janicke Liaaen; Galtung, Hilde & Hiorth, Marianne (2021). Development of a Liposomal Dry Mouth Product for Long-term Relief. Full text in Research Archive
• Hynne, Håvard; Aqrawi, Lara A.; Chen, Xiangjun; Amdal, Cecilie Delphin; Reppe, Sjur & Aass, Hans Christian Dalsbotten [Show all 14 contributors for this article] (2021). Cytokine profiling, clinical oral and ocular manifestations post radiotherapy. Full text in Research Archive
• Jensen, Janicke Liaaen (2021). Har pasienten Sjögrens syndrom? Full text in Research Archive
• Jensen, Janicke Liaaen (2021). Mye kunnskap om sjeldenhet. [Journal]. Nor Tannlegeforen Tid. Full text in Research Archive
• Jensen, Janicke Liaaen; Barkvoll, Pål & Cetrelli, Patrik (2021). Én innbygger – to journaler. Dagens medisin. ISSN 1501-4290. Full text in Research Archive
• Young, Alix; Jensen, Janicke Liaaen; Hove, Lene Hystad; Fjeld, Katrine Gahre & Blich, Carl Christian (2021). Et smil uten smerter? Full text in Research Archive
• Jensen, Janicke Liaaen (2021). Ut med tannhelse – inn med munnhelse som begrep! Full text in Research Archive
• Hynne, Håvard; Sandås, Elise Mørk; Elgstøen, Katja B. Prestø; Rootwelt, Helge; Galtung, Hilde Kanli & Utheim, Tor Paaske [Show all 7 contributors for this article] (2021). Metabolomics Identify Patterns Indicating Potential Biomarkers in Primary Sjögren’s Syndrome. Full text in Research Archive
• Jensen, Janicke Liaaen (2021). God tannhelse = god helse i fremtiden. [Journal]. Tara. Full text in Research Archive
• Jensen, Janicke Liaaen (2021). Sammenhengen mellom oral og generell helse. Full text in Research Archive
• Jensen, Janicke Liaaen; Barkvoll, Pål & Bjørnland, Tore (2021). Extra- and intraoral examination. In Bjørnland, Tore (Eds.), Nordic Textbook of Oral and Maxillofacial Surgery. Munksgaard Forlag. ISSN 9788762820128. p. 19–30. Full text in Research Archive
• Jensen, Janicke Liaaen (2020). Eldres munnehelse går under radaren. Forskning.no. ISSN 1891-635X. Full text in Research Archive
• Jensen, Janicke Liaaen (2020). Integrated oral and general health. Full text in Research Archive
• Diep, My Tien; Jensen, Janicke Liaaen; Sødal, Anne Thea Tveit; Young, Alix; Skudutyte-Rysstad, Rasa & Hove, Lene Hystad (2020). Are Xerostomia and Hyposalivation Common Problems Among 65-Year-Olds? Caries Research. ISSN 0008-6568. 54(4), p. 449–450. doi: 10.1159/000511860. Full text in Research Archive
• Jensen, Janicke Liaaen (2020). Hvordan påvirker revmatiske sykdommer generelt, og Sjögrens syndrom spesielt, oral helse? Full text in Research Archive
• Sapkota, Dipak; Thapa, Suraj Bahadur; Hasseus, Bengt & Jensen, Janicke Liaaen (2020). Saliva testing for COVID-19? British Dental Journal. ISSN 0007-0610. doi: 10.1038/s41415-020-1594-7. Full text in Research Archive
• Jensen, Janicke Liaaen (2020). Innledningsforedrag: Økt fokus på eldres munnhelse. Full text in Research Archive
• Jensen, Janicke Liaaen (2020). Bærekraftig alderdom - en sunn sjel med en sunn munnhule i et sunt lege. Full text in Research Archive
• Jensen, Janicke Liaaen (2019). Munn- og øyetørrhet, implikasjoner for generell helse og livskvalitet. Full text in Research Archive
• Jensen, Janicke Liaaen & Hove, Lene Hystad (2019). Eldres munnhelse: La oss fortelle historien om Berit. Full text in Research Archive
• Jensen, Janicke Liaaen (2019). Utvikling av nytt produkt mot tørr munn, innledninggsforedrag. Full text in Research Archive

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