Effect of Behcet's disease-associated oral ulcers on oral health related quality of life.

AIM: The current study assessed the clinical characteristics of patients suffering from Behcet's disease (BD)-associated oral ulcers and investigated the effect of these oral ulcers on the oral health-related quality of life (OHRQoL). METHODS: This study included BD patients suffering from active oral ulcers, defined by the revised International Criteria for BD (ICBD) criteria. We collected BD and oral ulcers characteristics. The oral ulcer activity index and OHRQoL were measured by composite index (CI) and Oral Health Impact Profile-14 (OHIP-14), respectively. RESULTS: Genital and ocular manifestations were the most frequent. Ocular manifestations were the main diagnostic manifestation. The mean age of BD diagnosis and first oral ulcer appearance were 32.15 ± 8.96 and 29.62 ± 9.04, respectively. Minor oral ulcers were more frequent; solitary or multiple. CI revealed that pain was more severe than functional disability. OHIP-14 showed that patients suffered more often from pain and difficulties in eating. Patients reported feeling tense, being irritable, doing usual job with difficulty, and having less satisfying life. CONCLUSION: BD-associated oral ulcers lead to poor quality of life. Female gender, multiple ulcers, and buccal mucosa were associated with more severe pain and functional disability as well as poorer quality of life.

Salivary expression of lncRNA DQ786243 and IL-17 in oral lichen planus: case-control study.

BACKGROUND: A growing number of studies has investigated IL-17 in OLP. However, its exact role and interactions are not fully determined. In addition, the literature investigating its salivary expression is limited. The scarcity in the literature studying lncRNAs was noticed, particularly with regards to correlating them with cytokines in OLP. In the current study, the salivary expression of lncRNA DQ786243 and IL-17 was assessed among different forms of OLP. METHODS: The study included 52 participants in four equal groups: reticular OLP, erythematous OLP, ulcerative OLP, and control group. All eligible OLP patients underwent conventional oral examination, along with basic charting of their demographic data, pain intensity using a visual analogue scale, and clinical evaluation using the Thongprasom et al. scale. The salivary expression of lncRNA DQ786243 and IL-17 was evaluated for all participants using qRT-PCR. Unstimulated whole saliva samples were used. Data were analyzed for statistical significance. RESULTS: No statistically significant difference was observed when comparing the mean age and gender distribution of the studied groups. A statistically significant difference was detected when comparing pain and clinical scores in the three OLP forms. The highest expression of both salivary biomarkers was noticed in ulcerative OLP, followed by erythematous OLP and reticular OLP, then the controls, with a significant difference between the studied groups. Upon comparing the salivary expression of DQ786243 in ulcerative and erythematous OLP, no significant difference was detected. No significant difference was detected when comparing salivary expression of IL-17 in erythematous OLP to the other OLP forms. CONCLUSIONS: The salivary expression of lncRNA DQ786243 and IL-17 was upregulated in OLP compared to healthy individuals. Besides, their expression increased when the severity of OLP was at its highest level in ulcerative OLP. There was a positive correlation between DQ786243 and IL-17. Trial registration The protocol was registered at ClinicalTrials.gov (NCT04503824). The date of registration is 07/08/2020.

Prevalence, Caries, Dental Anxiety and Quality of Life in Children with MIH in Brussels, Belgium.

Molar incisor hypomineralisation (MIH) is a dental enamel pathology responsible for unfavorable functional and aesthetic implications. The objective of this study is to assess the prevalence, dental anxiety, and quality of life related to oral health in children with MIH. In 14 schools in Brussels, Belgium, 290 children aged 8 to 9.5 answered Children's Fear Survey Schedule-Dental Subscale (CFSS-DS) and Child-Oral Impact on Daily Performance (C-OIDP) questionnaires to assess dental anxiety and quality of life related to oral health (OHRQoL). Oral examinations allowed us to detect MIH according to standardized criteria. The MIH prevalence was 18.6%. The Decayed, Missing and Filled Teeth index (DMFT index) of MIH patients was significantly higher than non-MIH patients (p < 0.001), mainly due to more restored teeth. There was no significant association between MIH and dental anxiety or OHRQoL. Caries in the deciduous dentition was significantly associated with impaired quality of life. The MIH prevalence in Brussels is comparable to other European countries. MIH had no significant impact on dental anxiety and OHRQoL in this sample. The dynamic nature of MIH lesions requires early diagnosis and management to limit the evolution of the severity of the lesions and their implications. It is possible that older age groups may present more symptoms, however, this would require a longitudinal study.

YAP1 Expression in Lichen Planus and Squamous Cell Carcinoma: Role in Disease Pathogenesis and Potential Therapeutic Target.

BACKGROUND: Lichen planus (LP), especially oral type, reported a potential risk of malignant transformation to squamous cell carcinoma (SCC). Yes-Associated Protein (YAP1), a key component of the Hippo pathway, acts as a transcription cofactor regulating expression of genes involved in cell proliferation, apoptosis, and migration. Therefore, it has been implicated in carcinogenesis of a wide variety of human cancers. OBJECTIVES: To study YAP1 expression in LP and SCC in comparison to normal control (NC) specimens. PATIENTS AND METHODS: This study was conducted on 50 NC specimens, 50 LP specimens, and 50 SCC specimens. They were categorized into 2 main groups; cutaneous (25 NC, 25 LP, 25 SCC), and oral (25 NC, 25 LP, 25 SCC). All specimens were examined for YAP1 antibody expression by immunohistochemistry and YAP1 mRNA expression by reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: In both cutaneous and oral groups; significant upregulation of YAP1 expressions was observed in SCC specimens followed by LP and then NC specimens in the same sequence. Its expression in SCC was found to be significantly higher in poorly and moderately differentiated types than well differentiated types. CONCLUSION: YAP1 may have a potential role in the pathogenesis of LP and oncogenesis and progression of SCC. Moreover, it could be considered as a novel therapeutic target for such cases.

Evaluation of diode laser versus topical corticosteroid in management of Behcet's disease-associated oral ulcers: a randomized clinical trial.

OBJECTIVES: The current trial was conducted to assess the effect of diode laser therapy compared to topical corticosteroid in management of oral ulcers of BD. MATERIALS AND METHODS: Fifty patients were divided randomly into two parallel groups. The first group received 980 nm diode laser; the second group received topical corticosteroid (0.1% triamcinolone acetonide). The outcome measures included oral ulcer activity index (composite index), pain (VAS), number of oral ulcers, healing time, and oral health-related quality of life (OHIP-14). The collected data were analyzed for any statistical significance. RESULTS: A statistically significant difference was detected between laser and corticosteroid groups favoring laser on comparing composite index and VAS scores on the first and third days and on comparing number of ulcers on the third and fifth days. A statistically significant difference was detected between laser and corticosteroid groups on comparing scores of the questions assessing discomfort with eating food, irritability with other people, taste worsening, unsatisfactory diet, and painful aching on the first and/or third days. No adverse effects were reported by participants of both groups. CONCLUSIONS: Diode laser is efficient safe treatment modality for management of BD-associated oral ulcers. Diode laser was more efficient than triamcinolone acetonide in controlling pain and reducing oral ulcer activity. CLINICAL RELEVANCE: Laser therapy is efficient safe modality that could spare BD patient from adding a new medication to their long list, being just one visit compared to other regular daily regimen medications. TRIAL REGISTRATION: ClinicalTrials.gov registration number: NCT03771768.

Gustatory Dysfunction among a Sample of Depressed Egyptian Adults under Antidepressants Therapy: A Retrospective Cohort Study.

It is quite clear that the ability to perceive taste sensations significantly affects food choice, which consequently affects health status in the long term. Gustatory dysfunction is a neglected symptom among the depressed patients and those under antidepressants therapy, although these patients are suspectable to oral problems, due to general self-negligence related to mental disease, fear of dental treatment, and side effects of varied medications utilized in psychiatry. This study is aimed at assessing gustatory thresholds (detection and recognition thresholds) among a sample of 30 depressed Egyptian adults under antidepressants therapy for at least 3 months or psychotherapy with age ranging from 20 to 50 years old, seeking the Psychiatric Clinic at the Faculty of Medicine, Cairo University, Egypt. These patients were distributed into three equal groups (tricyclic antidepressants (TCA), selective serotonin reuptake inhibitors (SSRIs), and psychotherapy) and were assessed for gustatory detection and recognition thresholds using the filter paper disc method through a scoring system. The participants were also divided into normal taste group in which both the detection and recognition scores were 1, while the scores from 2 till 5 were considered as hypogeusia group and the score of 6 was considered as dysgeusia group. The TCA group was statistically significant from the other 2 groups in sweet detection thresholds (p = 0.043) and sweet recognition thresholds (p = 0.007). Hypogeusia for sweet was statistically significant (p = 0.041), where it was more common among TCA (70%) than both SSRIs and the psychotherapy group (20%). Gustatory dysfunction was found to be mostly associated with TCA followed by SSRIs particularly for sweet taste thresholds. More attention has to be given to taste changes among these patients as oral health affects general health by causing considerable pain and by changing what people eat, their speech, and their quality of life and wellbeing. Proper awareness and evaluation of this problem will improve the quality of life for the depressed patients and avoid unnecessary treatment. This trial is registered with ClinicalTrials.gov ID: NCT03599011.

Stratification of methotrexate-induced oral ulcers in rheumatoid arthritis patients.

AIM: There is a deficiency in the data concerning the clinical forms of methotrexate-induced oral ulcers. This study was conducted to stratify clinical forms of methotrexate-induced oral ulcers in rheumatoid arthritis patients. METHODS: This study included rheumatoid arthritis patients receiving methotrexate as monotherapy. All eligible patients were subjected to thorough clinical examination and full history to identify oral events. Drug history, dose, and duration of MTX were recorded. RESULTS: Among 794 rheumatoid arthritis patients, mean methotrexate dose and duration were 14.3 mg/week and 5.2 years, respectively. Oral ulcers were detected in 6.2% of the patients and 30% of the patients reported previous oral ulcers. Among the detected oral ulcers, 44.9% manifested as deep irregular ulcers, 30.6% presented as aphthous-like ulcers, 14.3% were diffuse mucositis, and 10.2% appeared as lichenoid reaction. CONCLUSION: Methotrexate-induced oral ulceration could be localized or generalized. Localized forms were more noticed than generalized forms. Higher doses and longer durations of methotrexate were detected among patients with generalized oral ulcers.

Evaluation of topical human platelet lysate versus topical clobetasol in management of methotrexate-induced oral ulceration in rheumatoid arthritis patients: Randomized-controlled clinical trial.

BACKGROUND: There is no mainstay protocol for management of Methotrexate-induced oral ulcers; commonly used protocols are cessation of Methotrexate, folic acid treatment, corticosteroids or combination. A new era of oral ulcers management is represented by platelet concentrates. The current study assessed the effect of topical human platelet lysate compared to topical Clobetasol Propionate in management of methotrexate-induced oral ulceration in rheumatoid arthritis patients. METHODS: This randomized controlled clinical trial include 30 patients in two parallel groups (intervention - human platelet lysate, control - Clobetasol Propionate), with allocation ratio 1:1. Outcome measures were pain intensity using numerical rating scale, WHO scale for oral mucositis, measuring size of the largest ulcer and total number of oral ulcers. RESULTS: A statistically significant difference was detected between HPL and Clobetasol groups on comparing numerical rating scale, WHO mucositis scale, size and total number of oral ulcers throughout all visits. A considerable quick pain reduction and clinical improvement were noticed in HPL group compared to Clobetasol. CONCLUSION: Human platelet lysate has superior effect when compared to one of the most potent topical corticosteroids, Clobetasol Propionate, in reducing pain and clinical signs of Methotrexate-induced oral ulcers in patients with rheumatoid arthritis.

Symptom-based stratification of patients with primary Sjögren's syndrome: multi-dimensional characterisation of international observational cohorts and reanalyses of randomised clinical trials.

BACKGROUND: Heterogeneity is a major obstacle to developing effective treatments for patients with primary Sjögren's syndrome. We aimed to develop a robust method for stratification, exploiting heterogeneity in patient-reported symptoms, and to relate these differences to pathobiology and therapeutic response. METHODS: We did hierarchical cluster analysis using five common symptoms associated with primary Sjögren's syndrome (pain, fatigue, dryness, anxiety, and depression), followed by multinomial logistic regression to identify subgroups in the UK Primary Sjögren's Syndrome Registry (UKPSSR). We assessed clinical and biological differences between these subgroups, including transcriptional differences in peripheral blood. Patients from two independent validation cohorts in Norway and France were used to confirm patient stratification. Data from two phase 3 clinical trials were similarly stratified to assess the differences between subgroups in treatment response to hydroxychloroquine and rituximab. FINDINGS: In the UKPSSR cohort (n=608), we identified four subgroups: Low symptom burden (LSB), high symptom burden (HSB), dryness dominant with fatigue (DDF), and pain dominant with fatigue (PDF). Significant differences in peripheral blood lymphocyte counts, anti-SSA and anti-SSB antibody positivity, as well as serum IgG, κ-free light chain, ß2-microglobulin, and CXCL13 concentrations were observed between these subgroups, along with differentially expressed transcriptomic modules in peripheral blood. Similar findings were observed in the independent validation cohorts (n=396). Reanalysis of trial data stratifying patients into these subgroups suggested a treatment effect with hydroxychloroquine in the HSB subgroup and with rituximab in the DDF subgroup compared with placebo. INTERPRETATION: Stratification on the basis of patient-reported symptoms of patients with primary Sjögren's syndrome revealed distinct pathobiological endotypes with distinct responses to immunomodulatory treatments. Our data have important implications for clinical management, trial design, and therapeutic development. Similar stratification approaches might be useful for patients with other chronic immune-mediated diseases. FUNDING: UK Medical Research Council, British Sjogren's Syndrome Association, French Ministry of Health, Arthritis Research UK, Foundation for Research in Rheumatology. VIDEO ABSTRACT.

Systemic interferon type I and type II signatures in primary Sjögren's syndrome reveal differences in biological disease activity.

Objective: To assess the relationships between systemic IFN type I (IFN-I) and II (IFN-II) activity and disease manifestations in primary SS (pSS). Methods: RT-PCR of multiple IFN-induced genes followed by principal component analysis of whole blood RNA of 50 pSS patients was used to identify indicator genes of systemic IFN-I and IFN-II activities. Systemic IFN activation levels were analysed in two independent European cohorts (n = 86 and 55, respectively) and their relationships with clinical features were analysed. Results: Three groups could be stratified according to systemic IFN activity: IFN inactive (19-47%), IFN-I (53-81%) and IFN-I + II (35-55%). No patient had isolated IFN-II activation. IgG levels were highest in patients with IFN-I + II, followed by IFN-I and IFN inactive patients. The prevalence of anti-SSA and anti-SSB was higher among those with IFN activation. There was no difference in total-EULAR SS Disease Activity Index (ESSDAI) or ClinESSDAI between the three subject groups. For individual ESSDAI domains, only the biological domain scores differed between the three groups (higher among the IFN active groups). For patient reported outcomes, there were no differences in EULAR Sjögren's syndrome patient reported index (ESSPRI), fatigue or dryness between groups, but pain scores were lower in the IFN active groups. Systemic IFN-I but not IFN-I + II activity appeared to be relatively stable over time. Conclusions: Systemic IFN activation is associated with higher activity only in the ESSDAI biological domain but not in other domains or the total score. Our data raise the possibility that the ESSDAI biological domain score may be a more sensitive endpoint for trials targeting either IFN pathway.

Expression of CD163 in hereditary gingival fibromatosis: A possible association with TGF-ß1.

BACKGROUND: Although several studies have discussed some of the molecular and cellular changes associated with hereditary gingival fibromatosis (HGF), its pathogenesis is still largely unclear. This study was directed to detect and outline the degree of relationship between the immunophenotyped macrophages (M2) expressing CD163 and TGF-ß1 in patients with gingival overgrowth due to HGF. METHODS: Biopsies from 20 patients suffering from HGF and 20 normal control subjects were harvested, histologically and immunohistochemically stained then, analyzed and statistically compared and correlated for CD163 immunoexpression and TGF-ß1. RESULTS: All HGF specimens expressed TGF-ß1 by most of the connective tissue fibroblasts, with statistically high significant mean of area % (2.61 ± 0.41) compared to normal controls (0.11 ± 0.06; P = .001). All control specimens revealed negligible CD163 immunostaining of the few inflammatory cells found with a mean area of % (0.69 ± 0.12), while the specimens of HGF cases showed statistically significant higher CD163 expression (3.39 ± 0.75) at (P = .007). A statistically significant higher mean % of M2 cells expressing CD163 in relation to the total number of the inflammatory cells was revealed in HGF (34.46 ± 2.04) compared to the control group (16.36 ± 2.39; P-value ≤ .05). Moderate correlation between CD163 and TGF-ß1 was detected in HGF (r = .451; P-value < .05). CONCLUSIONS: CD163 and TGF-ß1 were clearly expressed in HGF cases compared to healthy control patients, with significant correlation. In HGF, the increase in CD 163-positive cells was specific and not dependent on the chronic gingival inflammation.

Studying the association between methylenetetrahydrofolate reductase (MTHFR) 677 gene polymorphism, cardiovascular risk and lichen planus.

BACKGROUND: There is a reported relation between hyperhomocysteinemia and lichen planus (LP). An increase in homocysteine (Hcy) and the risk of cardiovascular disease (CVD) in patients with methylenetetrahydrofolate reductase (MTHFR) mutation has been described. OBJECTIVE: To detect MTHFR (C677T) gene polymorphism, and to find its association with CVD risk, Hcy and folic acid levels in patients with LP. METHODS: This hospital-based case-control study included 110 patients with LP: 70 with cutaneous LP (CLP) and 40 with oral LP (OLP). A total of 120 age- and sex-matched healthy subjects were used as controls. Three millilitre venous blood sample was taken for detection of MTHFR gene polymorphism by PCR-RFLP technique and for measurement of the lipid profile. Hcy and folic acid were measured by ELISA. Hypertension was evaluated. RESULTS: There were significantly higher prevalence of hypertension with higher Hcy, triglycerides and cholesterol levels and lower folic acid and HDL levels among patients' groups. Hypertension with higher Hcy and cholesterol levels together with lower folic acid and HDL levels have been found in OLP when compared to CLP. Patients showed a significant higher percentage of the MTHFR 677 TT genotype (P=.003) and of the MTHFR 677 T allele (P=.042) compared to controls. Moreover, there was a higher prevalence of MTHFR 677 T allele in patients with CLP. CONCLUSION: MTHFR 677 gene polymorphism may be a risk factor for the development of the LP, and to predispose these patients to higher risk of CVD.

Clinically proven mtDNA mutations are not common in those with chronic fatigue syndrome.

BACKGROUND: Chronic Fatigue Syndrome (CFS) is a prevalent debilitating condition that affects approximately 250,000 people in the UK. There is growing interest in the role of mitochondrial function and mitochondrial DNA (mtDNA) variation in CFS. It is now known that fatigue is common and often severe in patients with mitochondrial disease irrespective of their age, gender or mtDNA genotype. More recently, it has been suggested that some CFS patients harbour clinically proven mtDNA mutations. METHODS: MtDNA sequencing of 93 CFS patients from the United Kingdom (UK) and South Africa (RSA) was performed using an Ion Torrent Personal Genome Machine. The sequence data was examined for any evidence of clinically proven mutations, currently; more than 200 clinically proven mtDNA mutations point mutations have been identified. RESULTS: We report the complete mtDNA sequence of 93 CFS patients from the UK and RSA, without finding evidence of clinically proven mtDNA mutations. This finding demonstrates that clinically proven mtDNA mutations are not a common element in the aetiology of disease in CFS patients. That is patients having a clinically proven mtDNA mutation and subsequently being misdiagnosed with CFS are likely to be rare. CONCLUSION: The work supports the assertion that CFS should not be considered to fall within the spectrum of mtDNA disease. However, the current study cannot exclude a role for nuclear genes with a mitochondrial function, nor a role of mtDNA population variants in susceptibility to disease. This study highlights the need for more to be done to understand the pathophysiology of CFS.

A Transcriptional Signature of Fatigue Derived from Patients with Primary Sjögren's Syndrome.

BACKGROUND: Fatigue is a debilitating condition with a significant impact on patients' quality of life. Fatigue is frequently reported by patients suffering from primary Sjögren's Syndrome (pSS), a chronic autoimmune condition characterised by dryness of the eyes and the mouth. However, although fatigue is common in pSS, it does not manifest in all sufferers, providing an excellent model with which to explore the potential underpinning biological mechanisms. METHODS: Whole blood samples from 133 fully-phenotyped pSS patients stratified for the presence of fatigue, collected by the UK primary Sjögren's Syndrome Registry, were used for whole genome microarray. The resulting data were analysed both on a gene by gene basis and using pre-defined groups of genes. Finally, gene set enrichment analysis (GSEA) was used as a feature selection technique for input into a support vector machine (SVM) classifier. Classification was assessed using area under curve (AUC) of receiver operator characteristic and standard error of Wilcoxon statistic, SE(W). RESULTS: Although no genes were individually found to be associated with fatigue, 19 metabolic pathways were enriched in the high fatigue patient group using GSEA. Analysis revealed that these enrichments arose from the presence of a subset of 55 genes. A radial kernel SVM classifier with this subset of genes as input displayed significantly improved performance over classifiers using all pathway genes as input. The classifiers had AUCs of 0.866 (SE(W) 0.002) and 0.525 (SE(W) 0.006), respectively. CONCLUSIONS: Systematic analysis of gene expression data from pSS patients discordant for fatigue identified 55 genes which are predictive of fatigue level using SVM classification. This list represents the first step in understanding the underlying pathophysiological mechanisms of fatigue in patients with pSS.

Effect of local application of tea tree (Melaleuca alternifolia) oil gel on long pentraxin level used as an adjunctive treatment of chronic periodontitis: A randomized controlled clinical study.

BACKGROUND: Conventional non-surgical periodontal therapy has been proven to be an effective treatment for patients with chronic periodontitis. Tea tree oil (TTO) can be used as adjunct to conventional periodontal therapy in patient with chronic periodontitis. The aim of this study was to evaluate the effectiveness of adjunctive treatment of TTO on the clinical parameters and the level of pentraxin-3 (PTX3) in chronic periodontitis. MATERIALS AND METHODS: A total of 40 patients with moderate to severe chronic periodontitis were divided into two groups, Group I received scaling and root planing (SRP) only, Group II received SRP and TTO gel. Clinical parameters were recorded and gingival crevicular fluid (GCF) samples were collected from each subject for measuring PTX3 levels at baseline, 1, 3 and 6 months after treatment. RESULTS: In all evaluation periods, there was statistically significant reduction in each of the studied clinical parameters and PTX3 level in Group II as compared with Group I. CONCLUSIONS: The local delivery of TTO gel in case of chronic periodontitis may have some beneficial effects to augment the results of the conventional periodontal therapy. Moreover, it places a focus on the value of monitoring GCF levels of PTX3 as a marker of periodontal tissue healing.

In-vitro evaluation of selected Egyptian traditional herbal medicines for treatment of Alzheimer disease.

BACKGROUND: Egyptians recognized the healing power of herbs and used them in their medicinal formulations. Nowadays, "Attarin" drug shops and the public use mainly the Unani medicinal system for treatment of their health problems including improvement of memory and old age related diseases. Numerous medicinal plants have been described in old literature of Arabic traditional medicine for treatment of Alzheimer's disease (AD) (or to strengthen memory). METHODS: In this study, some of these plants were evaluated against three different preliminary bioassays related to AD to explore the possible way of their bio-interaction. Twenty three selected plants were extracted with methanol and screened in vitro against acetylcholinesterase (AChE) and cycloxygenase-1 (COX-1) enzymes. In addition, anti-oxidant activity using DPPH was determined. RESULTS: Of the tested plant extracts; Adhatoda vasica and Peganum harmala showed inhibitory effect on AChE at IC50 294 µg/ml and 68 µg/ml respectively. Moreover, A. vasica interacted reversibly with the enzyme while P. harmala showed irreversible inhibition. Ferula assafoetida (IC50 3.2 µg/ml), Syzygium aromaticum (34.9 µg/ml) and Zingiber officinalis (33.6 µg/ml) showed activity against COX-1 enzyme. Potent radical scavenging activity was demonstrated by three plant extracts Terminalia chebula (EC50 2.2 µg/ml), T. arjuna (3.1 µg/ml) and Emblica officinalis (6.3 µg/ml). CONCLUSION: Interestingly, differential results have been obtained which indicate the variability of the mode of actions for the selected plants. Additionally, the reversible interaction of A. vasica against AChE and the potent activity of F. assafoetida against COX-1 make them effective, new and promising agents for treatment of AD in the future, either as total extracts or their single bioactive constituents.