RESUMO
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.
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Doenças Autoimunes , Vesículas Extracelulares , Ceratoconjuntivite Seca , Síndrome de Sjogren , Humanos , Síndrome de Sjogren/diagnóstico , Síndrome de Sjogren/genética , Vesículas Extracelulares/genética , RNA , RNA não TraduzidoRESUMO
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.
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Neoplasias de Cabeça e Pescoço , Síndrome de Sjogren , Xerostomia , Biomarcadores/metabolismo , Neoplasias de Cabeça e Pescoço/metabolismo , Neoplasias de Cabeça e Pescoço/radioterapia , Histonas/metabolismo , Humanos , Recidiva Local de Neoplasia/metabolismo , Proteômica , Saliva/metabolismo , Síndrome de Sjogren/metabolismo , Lágrimas/metabolismo , Xerostomia/metabolismoRESUMO
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.
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Autoanticorpos/sangue , Cadeias alfa de HLA-DQ/genética , Síndrome de Sjogren , Idade de Início , Autoimunidade/genética , Correlação de Dados , Feminino , Marcadores Genéticos/genética , Predisposição Genética para Doença , Variação Genética , Humanos , Masculino , Pessoa de Meia-Idade , Noruega/epidemiologia , Polimorfismo de Nucleotídeo Único , Análise de Sequência de DNA/métodos , Síndrome de Sjogren/classificação , Síndrome de Sjogren/genética , Síndrome de Sjogren/imunologia , Síndrome de Sjogren/fisiopatologia , Suécia/epidemiologiaRESUMO
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.
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Diabetes Mellitus Tipo 2 , Xerostomia , Idoso , Feminino , Humanos , Masculino , Noruega/epidemiologia , Saliva , Taxa Secretória , Xerostomia/epidemiologiaRESUMO
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.
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Lipídeos/análise , Síndrome de Sjogren/fisiopatologia , Adulto , Cromatografia Líquida de Alta Pressão/métodos , Feminino , Humanos , Lipídeos/classificação , Masculino , Espectrometria de Massas/métodos , Pessoa de Meia-Idade , Proteômica/métodos , Saliva/química , Saliva/metabolismo , Glândulas Salivares Menores/química , Glândulas Salivares Menores/patologia , Síndrome de Sjogren/imunologia , Síndrome de Sjogren/metabolismo , Lágrimas/química , Lágrimas/metabolismoRESUMO
OBJECTIVE: Quantitative research indicate increased anxiety and poorer mental health related quality of life (QoL) in individuals with oligodontia (congenital 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.
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Anodontia/psicologia , Anodontia/terapia , Saúde Bucal/estatística & dados numéricos , Qualidade de Vida/psicologia , Adaptação Psicológica , Adulto , Ansiedade/psicologia , Estética Dentária , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pesquisa Qualitativa , Adulto JovemRESUMO
OBJECTIVE: The aim of this study was to assess demographics, self-reported signs of ectodermal dysplasia (problems with hair, nails, skin and sweat glands), present teeth, previous dental treatment, psychological distress and QoL in individuals with oligodontia, and to explore the associations between these factors. We also aimed to compare the level of psychological distress and QoL between the study group and normative samples. METHODS: Forty-seven individuals with oligodontia registered at a resource centre in Norway were included in the study. The participants completed self-administered questionnaires on demographics, ED signs, dental treatments, psychological distress and QoL (overall, health-related- and oral health-related QoL). Relevant statistics (independent t-test, correlation analysis and hierarchical multiple regressions) were used. RESULTS: Thirty-five participants reported ED signs. Forty-one participants had tooth replacements (nine had removable dentures). Sixteen had ≤10 present teeth, 13 perceived dry mouth and seven were unemployed. Persons with ≤10 present teeth had higher anxiety- and depression-scores than those having >10 present teeth. Unemployment, dry mouth and removable dentures indicated poor health-related- and oral health related QoL. Compared to a normative sample; the study group had significantly poorer mental health (MH)-related QoL, mean (SD); (51.1(8.2) versus 46.8(9.3), p < .001) and more anxiety, mean (SD); (4.5(3.1) versus 6.7(3.6), p < .001). ED signs and treatments were most important for psychological distress and MH related QoL (MCS), whereas demographic parameters were most important for the other QoL measures. CONCLUSIONS: The psychological burden of oligodontia is significant, emphasizing the importance of a holistic approach by caregivers.
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Anodontia/psicologia , Displasia Ectodérmica/psicologia , Qualidade de Vida/psicologia , Xerostomia/psicologia , Adulto , Ansiedade/psicologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Noruega , Saúde Bucal/estatística & dados numéricos , Estresse Psicológico , Inquéritos e Questionários , Xerostomia/complicaçõesRESUMO
OBJECTIVE: To evaluate morbidity 1 week after mandibular third molar (3M) surgery in the authors' department. MATERIALS AND METHODS: A prospective 1-year clinical study of patients followed up for 1 week after 3M surgery was performed. Consecutive patients of 18 years or older having 3M surgery under local anaesthesia were included. Patients not able to attend a follow-up appointment after 1 week were excluded. Demographic data, indication for surgery and clinical findings were recorded. Outcome variables were days requiring analgesic, days absent from work/school and complications. All data recording was performed utilizing an e-infrastructure for clinical research (InReach, University Health Network, www.uhnsl.com). RESULTS: Three hundred and ninety-six patients were examined 1 week after surgery. Mean number of days requiring analgesics was 3.8 and mean number of days absent from work/school after surgery was 0.6. Minor complications were reported by 7% of patients. Female patients reported more days requiring analgesics compared to male patients. Smokers had a higher odds ratio for being absent ≥ 3 days. Prophylactic removal of 3Ms was associated with fewer days requiring analgesics and days absent from work/school as compared to teeth with local disease. CONCLUSION: Overall morbidity after 3M surgery was low. Compared to patients subjected to therapeutic removal of 3Ms, patients undergoing prophylactic removal seem to have less pain and a faster return to normal activities.
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Dente Serotino/cirurgia , Extração Dentária/efeitos adversos , Absenteísmo , Adolescente , Adulto , Analgésicos/uso terapêutico , Bases de Dados como Assunto , Cárie Dentária/cirurgia , Feminino , Seguimentos , Humanos , Cistos Maxilomandibulares/cirurgia , Masculino , Mandíbula/cirurgia , Pessoa de Meia-Idade , Noruega , Dor Pós-Operatória/etiologia , Pericoronite/cirurgia , Complicações Pós-Operatórias , Estudos Prospectivos , Fatores Sexuais , Fumar , Reabsorção de Dente/cirurgia , Resultado do Tratamento , Adulto JovemRESUMO
PURPOSE: The relationship between quality of life, psychological distress, and orofacial syndromes in children and adolescents has been reported in several studies. However, little is known about differences in psychological distress and quality of life among adults with different orofacial conditions. Therefore, the aims of this study were to examine and compare these factors among three groups of adults affected by Treacher Collins syndrome (TCS), cherubism, and oligodontia/ectodermal dysplasia (ED). METHODS: We included 11 individuals with TCS (mean age 46.9, SD 12.9 years), 15 with cherubism (mean age 50.3, SD 16.8 years), and 49 with oligodontia/ED (mean age 30.7, SD 15.6 years). The respondents completed questionnaires related to psychological distress and quality of life. RESULTS: The oligodontia/ED group had a significantly higher level of anxiety and worse mental health-related quality of life than both the TCS and cherubism groups. Adults with TCS reported the highest level of depression, and the lowest levels of overall quality of life, well-being, and physical health-related quality of life. The cherubism group displayed the best overall quality of life, well-being, and mental health. CONCLUSIONS: Psychological distress and quality of life differed in various orofacial conditions. This study provided insight into these aspects that may contribute to improved care.
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Querubismo/complicações , Displasia Ectodérmica/complicações , Disostose Mandibulofacial/complicações , Qualidade de Vida/psicologia , Estresse Psicológico/etiologia , Adulto , Ansiedade/etiologia , Querubismo/psicologia , Depressão/etiologia , Displasia Ectodérmica/psicologia , Feminino , Humanos , Masculino , Disostose Mandibulofacial/psicologia , Saúde Mental , Pessoa de Meia-Idade , Satisfação Pessoal , Estresse Psicológico/psicologia , Inquéritos e Questionários , Adulto JovemRESUMO
OBJECTIVE: Sjögren's Syndrome (SS) is a chronic autoimmune disease, leading to deficient secretion from salivary and lacrimal glands. Saliva production is normally increased by cholinergic innervation, giving rise to intracellular calcium signaling and water transport through water channels (aquaporins, AQPs). The aim of this study was to investigate possible pathophysiological changes in cell volume regulation, AQP expression and localization, and intracellular calcium signaling in glandular cells from SS patients compared to controls. MATERIALS AND METHODS: A total of 35 SS patients and 41 non-SS controls were included. Real time qPCR was combined with immunohistochemistry to analyze the mRNA expression and cellular distribution of AQP1, 3 and 5. Cell volume regulation and intracellular calcium signaling were examined in fresh acinar cells. RESULTS: We show for the first time a reduced mRNA expression of AQP1 and 5 in SS compared to controls, accompanied by a decrease in staining intensity of AQP1, 3 and 5 in areas adjacent to local lymphocytic infiltration. Furthermore, we observed that the SS cells' capacity for volume regulation was abnormal. Similarly, the calcium response after parasympathetic agonist (carbachol) stimulation was markedly decreased in SS cells. CONCLUSIONS: It is concluded that mRNA expression of AQP1 and 5, protein distribution of AQP1, 3 and 5, glandular cell volume regulation and intracellular calcium signaling are all altered in SS, pointing to possible pathophysiological mechanisms in SS.
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Sinalização do Cálcio/fisiologia , Glândulas Salivares/patologia , Síndrome de Sjogren/fisiopatologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Aquaporina 1/análise , Aquaporina 3/análise , Aquaporina 5/análise , Aquaporinas/análise , Sinalização do Cálcio/efeitos dos fármacos , Carbacol/farmacologia , Tamanho Celular , Agonistas Colinérgicos/farmacologia , Estudos de Coortes , Feminino , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Saliva/química , Saliva/metabolismo , Glândulas Salivares/efeitos dos fármacos , Glândulas Salivares/metabolismo , Método Simples-Cego , Síndrome de Sjogren/patologiaRESUMO
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.
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Ageusia , COVID-19 , Transtornos do Olfato , Humanos , COVID-19/complicações , COVID-19/epidemiologia , Ageusia/etiologia , Anosmia , Estudos Transversais , SARS-CoV-2 , Disgeusia/epidemiologia , Disgeusia/etiologia , Transtornos do Olfato/etiologia , Transtornos do Olfato/complicações , OlfatoRESUMO
OBJECTIVE: The aim of the present study was to describe the prevalence of clinical pulmonary manifestations in primary SS (pSS), and based on registry data, to assess quality of life (QoL) and mortality in these patients. METHODS: Patients with pSS consecutively included in the Norwegian systemic CTD and vasculitis registry (NOSVAR) were investigated for pulmonary manifestations when presenting with clinical pulmonary symptoms. Pulmonary involvement was defined as typical abnormalities identified with high-resolution CT (HRCT) and/or pulmonary function tests (PFTs). RESULTS: Among patients referred from our primary area, Oslo (n = 117), lung involvement was found in 26 patients (22%). In our total cohort (n = 216), 59 patients (27%) were affected. A higher rate of pulmonary complications and trends towards longer disease duration and higher age indicated a selection of more complicated cases referred from outside our primary area. Abnormal HRCTs were found in 50 patients (23%) and PFTs in 34 patients (16%). The Medical Outcomes Study 36-Item Short-Form Health Survey Physical Functioning subscore, was significantly reduced in patients with lung involvement (P = 0.03). Furthermore, a 4-fold increased risk of dying after 10 years of disease among patients with lung involvement (n = 10, 17%) compared with those without lung involvement (n = 7, 4.5%) (P = 0.002) was found. CONCLUSION: We found a high population-based prevalence of clinical pulmonary involvement (22%) among patients with pSS. Moreover, patients with lung involvement had reduced QoL represented by the subscale Physical Functioning, and mortality was increased.
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Pneumopatias/epidemiologia , Qualidade de Vida , Síndrome de Sjogren/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Comorbidade , Feminino , Humanos , Pneumopatias/mortalidade , Pneumopatias/psicologia , Masculino , Pessoa de Meia-Idade , Noruega/epidemiologia , Prevalência , Sistema de Registros , Testes de Função Respiratória , Estudos Retrospectivos , Síndrome de Sjogren/mortalidade , Síndrome de Sjogren/psicologia , Análise de SobrevidaRESUMO
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.
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Unidade Hospitalar de Psiquiatria , Xerostomia , Humanos , Adulto , Saúde Bucal , Qualidade de Vida , Xerostomia/complicações , Xerostomia/diagnóstico , SalivaRESUMO
Fine mapping and bioinformatic analysis of the DDX6-CXCR5 genetic risk association in Sjögren's Disease (SjD) and Systemic Lupus Erythematosus (SLE) identified five common SNPs with functional evidence in immune cell types: rs4938573, rs57494551, rs4938572, rs4936443, rs7117261. Functional interrogation of nuclear protein binding affinity, enhancer/promoter regulatory activity, and chromatin-chromatin interactions in immune, salivary gland epithelial, and kidney epithelial cells revealed cell type-specific allelic effects for all five SNPs that expanded regulation beyond effects on DDX6 and CXCR5 expression. Mapping the local chromatin regulatory network revealed several additional genes of interest, including lnc-PHLDB1-1. Collectively, functional characterization implicated the risk alleles of these SNPs as modulators of promoter and/or enhancer activities that regulate cell type-specific expression of DDX6, CXCR5, and lnc-PHLDB1-1, among others. Further, these findings emphasize the importance of exploring the functional significance of SNPs in the context of complex chromatin architecture in disease-relevant cell types and tissues.
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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.
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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.
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Neoplasias de Cabeça e Pescoço , Síndrome de Sjogren , Xerostomia , Neoplasias de Cabeça e Pescoço/metabolismo , Humanos , Metabolômica , Nucleotídeos de Pirimidina/análise , Nucleotídeos de Pirimidina/metabolismo , Saliva/metabolismo , Síndrome de Sjogren/metabolismo , Xerostomia/metabolismoRESUMO
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.
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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.
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Síndromes do Olho Seco , Xerostomia , Idoso , Estudos de Coortes , Síndromes do Olho Seco/diagnóstico , Síndromes do Olho Seco/epidemiologia , Humanos , Noruega , Saliva , Inquéritos e Questionários , Lágrimas , Xerostomia/diagnóstico , Xerostomia/epidemiologiaRESUMO
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.
Assuntos
Estudo de Associação Genômica Ampla , Síndrome de Sjogren , Predisposição Genética para Doença , Humanos , Polimorfismo de Nucleotídeo Único , Síndrome de Sjogren/genéticaRESUMO
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.