Incidence of alveolar osteitis after mandibular third molar surgery. Can inflammatory cytokines be identified locally?

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.

Oral disorders, saliva secretion, and oral health-related quality of life in patients with primary Sjögren's syndrome.

Chemosensory function, burning sensations in the tongue (BST), halitosis, saliva secretion, and oral health-related quality of life (OHRQoL) were investigated in patients with primary Sjögren's syndrome (pSS). In 31 patients with pSS and 33 controls, olfactory and gustatory functions were evaluated. Self-reported complaints of dysgeusia, BST, and halitosis were recorded. Saliva secretion rates were measured and OHRQoL was assessed using the short-form Oral Health Impact Profile (OHIP-14). Patients had significantly lower olfactory (8.8 ± 3.5 vs. 10.7 ± 1.2) and gustatory (18.9 ± 7.1 vs. 25.4 ± 4.3) scores than controls, and significantly more patients complained of dysgeusia (58.1% vs. 0%), BST (54.8% vs. 6.1%), and halitosis (41.9% vs. 0%). A significantly greater proportion of patients with pSS had ageusia (19% vs. 0%), hypogeusia (32% vs. 12%), anosmia (13% vs. 0%), or hyposmia (29% vs. 9%). Significantly lower saliva secretion rates (ml min-1 ) were observed in patients with pSS for stimulated (0.62 ± 0.40 vs. 1.57 ± 0.71) and unstimulated (0.08 ± 0.07 vs. 0.29 ± 0.17) saliva. The mean OHIP-14 score was significantly higher in patients with pSS (16.2 ± 10.8 vs. 2.7 ± 3.1) and was positively correlated with dysgeusia, BST, and halitosis. In conclusion, patients with pSS reported higher occurrence of dysgeusia, BST, and halitosis, and demonstrated relatively impaired chemosensory and salivary functions. The patients' poorer OHRQoL was associated with dysgeusia, BST, and halitosis.

The Hippo signaling pathway is required for salivary gland development and its dysregulation is associated with Sjogren's syndrome.

Sjogren's syndrome (SS) is a complex autoimmune disease that primarily affects salivary and lacrimal glands and is associated with high morbidity. Although the prevailing dogma is that immune system pathology drives SS, increasing evidence points to structural defects, including defective E-cadherin adhesion, to be involved in its etiology. We have shown that E-cadherin has pivotal roles in the development of the mouse salivary submandibular gland (SMG) by organizing apical-basal polarity in acinar and ductal progenitors and by signaling survival for differentiating duct cells. Recently, E-cadherin junctions have been shown to interact with effectors of the Hippo signaling pathway, a core pathway regulating the organ size, cell proliferation, and differentiation. We now show that Hippo signaling is required for SMG-branching morphogenesis and is involved in the pathophysiology of SS. During SMG development, a Hippo pathway effector, TAZ, becomes increasingly phosphorylated and associated with E-cadherin and α-catenin, consistent with the activation of Hippo signaling. Inhibition of Lats2, an upstream kinase that promotes TAZ phosphorylation, results in dysmorphogenesis of the SMG and impaired duct formation. SMGs from non-obese diabetic mice, a mouse model for SS, phenocopy the Lats2-inhibited SMGs and exhibit a reduction in E-cadherin junctional components, including TAZ. Importantly, labial specimens from human SS patients display mislocalization of TAZ from junctional regions to the nucleus, coincident with accumulation of extracellular matrix components, fibronectin and connective tissue growth factor, known downstream targets of TAZ. Our studies show that Hippo signaling has a crucial role in SMG-branching morphogenesis and provide evidence that defects in this pathway are associated with SS in humans.

Tear and Saliva Metabolomics in Evaporative Dry Eye Disease in Females.

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.

Using machine learning model explanations to identify proteins related to severity of meibomian gland dysfunction.

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.

Oral distress in primary Sjögren's syndrome: implications for health-related quality of life.

The aims of the study were to evaluate oral distress in patients with primary Sjögren's syndrome (pSS) compared with age- and sex-matched Norwegian normative data, to estimate the occurrence of oral symptoms in pSS, and to evaluate the impact of oral distress on health-related quality of life (HRQoL). The Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36) was used to assess HRQoL, and the Oral Health Impact Profile 14 (OHIP-14) was used to measure oral distress. Of the 246 pSS patients invited to participate in the study, 177 (72%) responded. Data were analysed for the female participants (n = 163). Significant deviations from normative estimates were found in all OHIP-14 item results, and the findings indicated a high level of oral distress among the pSS patients. Health-related quality of life was decreased among pSS patients, with the largest deviations from normative estimates related to general health and role physical. The patients with high levels of oral distress scored significantly lower than patients with low levels of oral distress in five of the SF-36 subscales, indicating that oral conditions have a marked impact on general quality of life. In conclusion, oral distress in pSS is pronounced and severe, and should receive increased attention with a view to improving the quality of life for these patients.

Gene expression alterations in salivary gland epithelia of Sjögren's syndrome patients are associated with clinical and histopathological manifestations.

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.

P2 Receptors as Therapeutic Targets in the Salivary Gland: From Physiology to Dysfunction.

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.

Dietary Intake, Body Composition, and Oral Health Parameters among Female Patients with Primary Sjögren's Syndrome.

There is limited knowledge about dietary intake and body composition among patients with primary Sjögren's syndrome. We assessed dietary intakes with 24-h recalls and body composition with anthropometry and bioelectrical impedance in 20 female patients. Various scoring tools were used to assess oral health. The patients had a lower energy percentage (E%) from carbohydrates (p = 0.02) and a higher E% from fat (p = 0.01) compared to a reference group. The lower intake of carbohydrates was due to a lower bread intake (p = 0.04), while the higher intake of fat was due to a higher intake of butter, margarine, and oil (p = 0.01). The patients ate more than twice (p = 0.02) as much fish as the reference group. The compliance to recommended intakes of macro- and micronutrients was good. Forty-percent of the patients were overweight/obese. Increased intake of beverages was observed in patients with severe xerostomia and/or low oral health-related quality of life, whereas reduced fat intake was found in hyposmic patients. In conclusion, the dietary intake among the patients was not much different from the reference group and complied with recommendations. Most oral health parameters were not associated with nutrient intakes. Specific dietary guidelines are probably not needed to ensure adequate nutrition among such patients.

Treatment outcome of dental implants in the esthetic zone: a 12- to 15-year retrospective study.

In the mid-nineties, 27 patients received 31 implant-supported crowns in the anterior maxillary region, and 12 to 15 years later, 18 patients (67%) with 22 implants (67%) participated in a retrospective study evaluating implant survival, bone loss, prosthetic complications, patient satisfaction, and patient and professional evaluation of esthetics. One implant was lost because of implant fracture after 10 years. Mean marginal bone loss was 1.53 mm (standard error ± 0.17 mm). In 6 patients, 6 crowns were replaced and 1 repaired. In 3 patients, 3 crowns had minor unrepaired porcelain fractures. Implant survival was 95.5%, and, despite the high frequency of prosthetic complications, patients were generally very satisfied with the long-term treatment outcome.