Search Results (263)

Pleomorphic adenomas (PAs) are benign mixed tumors of the salivary glands that usually present with morphological characteristics consisting of epithelial and myoepithelial cells and a chondromyxoid stromal component. Atypical cells; squamous, osseous, lipomatous, endocrine-like or apocrine metaplasia; aspects of invasion (vascular, perineural, in adjacent tissues or the capsule); necrosis; and unusual dimensions were reported as uncommon aspects that can be encountered in PAs. This study consisted of a retrospective analysis of the morphological characteristics of PAs, aiming to identify their unusual features and prevent misdiagnosis. We discuss the diverse morphological aspects of PAs, with particular emphasis on the challenges associated with their diagnosis. Full article

Xerostomia is a common and debilitating condition caused by salivary gland dysfunction, frequently associated with primary Sjögren’s syndrome and head and neck radiotherapy. Current management is largely symptomatic and does not address underlying glandular injury. Extracellular vesicles (EVs), including exosomes, have emerged as candidate mediators of intercellular communication that have been proposed for diagnostic and therapeutic applications; however, their translational relevance to xerostomia remains uncertain and is currently supported only by exploratory evidence. This scoping review aimed to map and interpret current evidence on EV-based approaches in xerostomia and salivary gland dysfunction. A scoping review was conducted in accordance with “Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR)” checklist. Twenty-five articles were included, comprising 14 primary studies and 11 review articles. Studies were analysed based on application focus, methodological characteristics, reported outcomes, and translational readiness. Most primary studies focused on EVs as diagnostic biomarkers or their roles in immune–epithelial signalling. Therapeutic research was limited and largely confined to human-relevant translational models, namely human peripheral blood mononuclear cell (PBMC) assays and freshly resected human salivary gland tissue-maintained ex vivo. Outcomes were predominantly molecular and cellular, with minimal assessment of salivary flow or patient-reported symptoms. The current evidence base, although biologically plausible, remains exploratory: most included studies are mechanistic, and no clinical efficacy studies in xerostomia were identified. A substantial gap therefore persists between molecular findings and clinically meaningful outcomes, and further translational research is required before any conclusions can be drawn regarding the clinical utility of EV-based approaches. Full article

Introduction: Labor pain is among the most intense forms of acute pain, mediated in part by excitatory glutamatergic neurotransmission within central nociceptive pathways. Glutamate plays a key role in spinal dorsal horn signaling and central sensitization, yet its peripheral dynamics during labor and in response to different analgesic modalities remain unclear. This exploratory study aimed to evaluate whether maternal salivary glutamate levels differ between epidural labor analgesia and systemic morphine analgesia during normal vaginal delivery. Method: In this observational comparative study, 36 women were selected to either epidural analgesia (n = 16) or systemic morphine analgesia (n = 20). Salivary samples were collected during active labor and analyzed for glutamate concentration using a validated enzymatic colorimetric assay. Clinical and demographic data were recorded. Non-parametric tests were applied due to non-normal distribution of glutamate levels. Results: Baseline maternal and perinatal characteristics were comparable between groups. Median salivary glutamate levels were higher in the epidural group than in the morphine group (5.32 nmol/µL [IQR 2.83–8.00] vs. 3.99 nmol/µL [IQR 2.26–8.03]), but the difference was not statistically significant (p = 0.599). Glutamate concentrations showed marked inter-individual variability (0.14–29.89 nmol/µL) and a right-skewed distribution. No significant associations were observed between glutamate levels and maternal age, Body Mass Index, gestational age, birth weight, or obstetric comorbidities. Conclusion: In this exploratory cohort, maternal salivary glutamate concentrations did not differ significantly between epidural labor analgesia and systemic morphine analgesia during labor. The variability observed suggests complex and heterogeneous regulation of peripheral glutamatergic activity in parturition. Further larger-scale studies integrating central and peripheral measurements are warranted. Full article

Salivary gland tumors, although relatively rare, exhibit a wide histological variety. The most modern classifications list over 30 histotypes, both benign and malignant, with widely varying morphological, epidemiological, and clinical characteristics, sometimes even within the same tumor type based on grading. The consequence of these characteristics is that regarding the diagnosis and treatment of salivary gland tumors, there have been, and still are, some certainties, many uncertainties, and some myths not supported by irrefutable studies, but which are cited, repeated, and taken for granted from one article to the next. The purpose of this narrative review is to analyze the most important and controversial opinions regarding the diagnosis and treatment of salivary gland tumors of the head and neck, and, in particular, those of the most frequent and/or problematic histological types, both malignant and benign. To this end, approximately one hundred historical and recent studies on these topics were analyzed. Full article

Background and Clinical Significance: Childhood-onset Sjögren’s disease (cSjD) is a rare autoimmune disorder that remains challenging to diagnose because of its heterogeneous clinical presentation and the frequent absence of classic sicca symptoms at disease onset. Recurrent parotitis and systemic manifestations often predominate in pediatric patients, contributing to diagnostic delay and potential irreversible glandular damage. Early recognition is essential to prevent complications and improve long-term outcomes. Case Presentation: We report the case of a 17-year-old female diagnosed with primary Sjögren’s disease following a prolonged history of recurrent parotid involvement and progressive glandular dysfunction. Comprehensive evaluation revealed positive anti-SSA antibodies, hypergammaglobulinemia, characteristic salivary gland ultrasonography abnormalities, and a positive minor salivary gland biopsy, resulting in fulfillment of all domains of the 2016 ACR/EULAR classification criteria. The patient also exhibited unusual vascular findings, including carotid atheromatous calcifications in the absence of traditional cardiovascular risk factors. Conclusion: This case highlights the diagnostic complexity of cSjD and underscores the value of a multimodal diagnostic approach integrating clinical assessment, serology, imaging, and histopathology. The presence of early vascular abnormalities broadens the spectrum of potential extraglandular manifestations and emphasizes the need for comprehensive evaluation and long-term monitoring in affected patients. Full article

Background/Objectives: Hyalinizing clear cell carcinoma (HCCC) and clear cell odontogenic carcinoma (CCOC) are rare clear cell neoplasms with overlapping histopathological features. This study aimed to compare their clinicopathological characteristics, particularly in anatomically challenging sites such as the palate and maxilla. Methods: Three analyses were performed. First, an unpublished series of five HCCC and three CCOC cases was evaluated for diagnostic histopathological features. Second, a PRISMA-ScR-guided literature review of 58 HCCCs and 45 CCOCs restricted to tumours arising in intraoral minor salivary glands, major salivary glands and gnathic bones published between 2000 and 2025 was conducted using PubMed. Third, a sub-analysis compared palatal HCCC and maxillary CCOC (25 vs. 14 cases), integrating literature and unpublished cases. Results: The case series and overall literature review showed that HCCC and CCOC predominantly occurred in adults (mean age, case series: 50.8 years; literature: 56.33 years for HCCC and 61 vs. 54.11 years for CCOC) with a female predilection (case series: 60%; literature: 68%) and generally exhibited clinically indolent behaviour. The site of occurrence, soft tissue (HCCC) versus intraosseous location (CCOC), was the principal distinguishing feature. No marked differences were observed between the two tumours in either the overall literature analysis or the site-specific sub-analysis. However, CCOC at maxillary/palatal sites presented with a higher number of larger lesions and higher number of cases with nodal metastasis compared with HCCC, most probably indicating delayed clinical detection rather than intrinsic aggressiveness of CCOC. Histopathological overlap was considerable; however, diffuse dense hyalinization (4/5), focal glandular differentiation (2/5), mucous-secreting cells (4/5) and salivary gland association (5/5) favoured HCCC, whereas patchy hyalinization (3/3), larger tumour lobules (3/3) and peripheral palisading (2/3) favoured CCOC. Conclusions: HCCC and CCOC demonstrate clinicopathological similarities and shared EWSR1 rearrangement, supporting a close biological relationship. The considerable overlap between these tumours support the hypothesis that CCOC may represent the intraosseous counterpart of HCCC and highlight the importance of integrated clinicopathological assessment and further clarification in future WHO classifications. Full article

Background: Korean registered nurses face substantial cumulative occupational stress. Telomere length, a biomarker of cellular aging, is increasingly used in occupational stress research, but evidence on early-career Korean nurses is scarce. This study examined the association between occupational characteristics and telomere length in female nurses aged 20–39 years. Methods: Sixty-eight female nurses from a tertiary hospital in South Korea completed the questionnaires. We assessed demographics, occupational factors, burnout (Maslach Burnout Inventory), and sleep quality (Pittsburgh Sleep Quality Index—Korean [PSQI-K]). Salivary telomere length was measured using quantitative polymerase chain reaction (qPCR). Data were analyzed using t-tests, ANOVA with a Bonferroni post hoc test, Pearson correlations, and multivariable linear regression. Results: Participants showed moderate to high burnout levels (Emotional Exhaustion [EE] = 24.78 ± 10.96), with 41.2% exceeding the high EE threshold. Sleep quality was poor (PSQI-K = 7.90 ± 3.07), with 82.4% exceeding the cut-off. Univariable analyses revealed that younger age, unmarried status, shorter work experience, and higher personal accomplishment were associated with longer telomeres (all p < 0.05); multivariable analysis identified only age group as a significant predictor (B = −2.055 kb for nurses aged ≥30 years compared to those <30 years, p < 0.001). The model explained 83% of the variance in telomere length. Shift work, burnout, and sleep quality were not significantly associated with telomere length after controlling for age. Conclusions: Age was the main factor associated with telomere length in young female nurses, suggesting that biological manifestation of occupational effects may require longer exposure. The high prevalence of burnout and sleep disturbances warrants immediate organizational intervention. Saliva-based qPCR demonstrated reliable precision as a non-invasive method for biological monitoring in occupational health research. These findings provide a basis for future longitudinal studies examining the cumulative effects of occupational stress and inform targeted wellness interventions for early-career nurses. Full article

Indole, a volatile metabolite produced by bacterial tryptophanase (encoded by tnaA) during tryptophan metabolism, contributes to oral malodor and may influence the progression of periodontitis. However, the genetic features underlying strain-specific indole production and its association with bacterial virulence remain unclear. Analysis of a previously published periodontitis cohort revealed that periodontitis severity was associated with salivary indole-related metabolic signatures, which were positively correlated with the abundance of Porphyromonas gingivalis (P. gingivalis). Further analysis showed that W83, a reference strain previously reported to exhibit relatively high virulence-associated characteristics, produced significantly higher levels of indole than ATCC 33277 under the experimental conditions. Comparative genomic analysis of 36 complete P. gingivalis genomes showed that the amino acid sequences of TnaA were highly conserved. However, the transposase region adjacent to tnaA differed among strains: previously reported high-virulence strains, including W83, W50, and A7436, harbored the IS5-family transposase ISPg1, whereas several low-virulence reference strains carried the IS982-family transposase IS195. In saliva samples from periodontitis patients, ISPg1 expression was positively correlated with tnaA expression, and both were associated with periodontal clinical parameters. Together, these findings indicate that transposase-associated genomic variation near tnaA is associated with strain-specific tryptophan-indole metabolism, virulence-associated gene expression, and periodontal clinical parameters, while direct causality remains to be established in future functional studies. Full article

Background: Existing therapies for xerostomia are primarily symptomatic, providing temporary mucosal hydration without addressing underlying pathological changes in the oral cavity. In this context, medicated chewing gums containing ascorbic acid and lysozyme hydrochloride offer a promising approach, combining antimicrobial, antioxidant, and trophic effects with physiological salivary stimulation and prolonged local delivery. Methods: For the development of compressed chewing gum formulation, the physicochemical (particle size distribution, moisture absorption capacity, and microscopic characteristics) and technological (flowability, angle of repose, bulk and tapped density, Carr’s index (CI), and Hausner ratio (HR)) properties of the active substances and their formulations with excipients were evaluated. Pharmacological activity was assessed in an atropine-induced xerostomia rat model. Results: The physical mixture of all components showed inferior flow properties compared with the formulation containing pre-granulated lysozyme hydrochloride, as evidenced by higher Carr’s index and Hausner ratio values (CI = 17, HR = 1.20 vs. CI = 13, HR = 1.14), indicating improved processability after pre-granulation. The effect of relative humidity during formulation was also assessed, with an optimal level of 40% required to ensure process stability due to the hygroscopic nature of the components. Based on these data, technological approaches ensuring processability were established, including wet pre-granulation of lysozyme hydrochloride and premixing of ascorbic acid to reduce oxidation risk. These approaches resulted in an optimized compression mass with excellent flowability (CI = 8, HR = 1.09), suitable for the preparation of medicated chewing gum. An optimal compression force (7 kN) ensured suitable rheological and textural properties, resulting in rapid and nearly complete release of the active ingredients from the medicated chewing gum, consistent with kinetic analysis. In vivo studies using an atropine-induced xerostomia rat model demonstrated that the combination of ascorbic acid and lysozyme hydrochloride significantly increased salivary secretion (2.17-fold vs. control pathology group) and reduced salivary gland mass coefficients (by 13–18% compared with the control pathology group and groups receiving individual active ingredients), alongside improvement of oxidative stress markers, including a reduction in TBA-reactants (by 51.6%) and an increase in catalase activity (by 51.0%). Conclusions: The developed medicated chewing gum showed favorable technological properties, efficient release of active ingredients, and anti-xerostomic activity in vivo, indicating its potential for xerostomia relief and oral health support. Full article

Oral squamous cell carcinoma (OSCC) is characterized by consistently high mortality rates (≤60%) despite therapeutic advances. This is attributable to diagnostic delays arising from the asymptomatic early stages and time-consuming protocols. Hence, the establishment of reliable biomarkers for the routine assessment of the oral mucosa is imperative. MicroRNAs (miRNAs), key epigenetic regulators of gene expression, represent ideal candidates given their characteristic dysregulation across different pathologies. Here, we aimed to identify novel OSCC-specific miRNAs for the saliva-based detection of OSCC from the presymptomatic stage of early invasion. Through a multistep bioinformatic workflow, four miRNAs (miR-20b-5p, miR-484, miR-185-5p and miR-181d-5p) were identified as disease-specific since they simultaneously regulated >65% of a panel encompassing the 15 primarily overexpressed oncogenes in OSCC and a stage-specific panel including the six upregulated genes that genetically define the malignant stages of sequential oral carcinogenesis. The salivary expression of the identified miRNAs was studied in 31 OSCC patients and 31 healthy controls, using quantitative real-time PCR, followed by statistical analysis and an evaluation of the diagnostic accuracy. All studied miRNAs were significantly downregulated in the saliva of OSCC patients compared to controls (miR-484, p < 0.001; miR-181d-5p, p < 0.001; miR-185, p = 0.008; miR-20b, p = 0.026) and exhibited combinatory diagnostic performance of 95.4% (p < 0.001) for OSCC detection. Their expression remained uninfluenced by lifestyle and clinicopathological parameters, including smoking/alcohol, tumor site, grade and disease stage. The proposed 4-miRNA panel exhibits high diagnostic performance for the early, saliva-based detection of OSCC, irrespective of histopathological and lifestyle confounders, highlighting its potential as a robust non-invasive screening tool. Full article

Metabolic changes in saliva are known to be closely associated with the presence of non-oral cancers, particularly breast cancer. The diagnostic and prognostic potential of salivary biomarkers in breast cancer has been demonstrated, but their applicability for assessing therapy response has not yet been established. The aim of this study was to comprehensively analyze clinical, pathological, molecular, and salivary characteristics when assessing the response to neoadjuvant chemotherapy for breast cancer. The study included 361 breast cancer patients undergoing their first course of chemotherapy and 127 healthy volunteers without breast pathologies. Saliva samples were collected from all volunteers before treatment. Saliva analysis results for amino acids, lipids, and tumor markers were compared with tumor pathomorphism assessment after breast cancer surgery. The proportion of patients with a complete response to therapy was statistically significantly lower after menopause, and in those with HER2-negative breast cancer, moderate tumor differentiation, and high estrogen and progesterone receptor expression. For the first time, a body mass index (BMI) greater than 25 and low HER2 expression (HER2-low) were shown to have an unfavorable prognosis. The criterion for selecting informative salivary metabolites was a multidirectional change in minimal and complete pathological responses to therapy compared to healthy controls. Thus, prognostically favorable signs were a decrease in the concentration of urea below 7.5 mmol/L (OR = 1.921; 95% CI 1.061–4.270; p = 0.0342), a decrease in the area of the absorption band at 2957 cm⁻¹ below 24 (OR = 3.875; 95% CI 1.160–12.70; p = 0.0003), and an increase in the concentration of cancer antigen CA27.29 above 3 U/L (OR = 2.138; 95% CI 1.021–7.273; p = 0.0343) and CA-15-3 above 39 U/L (OR = 3.896; 95% CI 1.062–14.07; p = 0.0072). With a simultaneous increase in both CA27.29 and CA15-3, the probability of a complete response to therapy increased (OR = 4.288; 95% CI 1.056–17.09; p = 0.0013). Multivariate analysis showed that an independent prognostic indicator, along with the expression status of HER2, estrogen receptors, differentiation degree, BMI, and menopause status, was the concentration of CA15-3 in saliva (AUC = 0.789, 95% CI: 0.737–0.842, p = 0.0001). Identifying new markers will help physicians formulate treatment plans tailored to a patient’s individual risk factors, leading to increased survival and improved quality of life. Full article

Pupil area reflects not only the light reflex but also cognitive activity and arousal, and has been proposed as a non-invasive indicator of stress. However, the temporal characteristics of pupillary responses during cognitive stress tasks and their associations with other physiological and psychological measures remain unclear. This study examined cognitive stress responses during an N-back task using pupil area and changes in salivary alpha-amylase (sAA). Twenty-nine university and graduate students (mean age = 21.07 ± 0.91 years; 4 males, 25 females) participated. Pupil area was continuously recorded during a 2-back task. Salivary alpha-amylase was measured before (pre) and immediately after the task (post), and the change in sAA (post–pre) was calculated. Subjective stress responses and mood states were assessed using the SRS-18 and TDMS. A notable gender imbalance (predominantly female) limits the generalizability of findings, and future studies should aim for more balanced samples. Pupil area significantly decreased in the latter half of the task, consistent with a time-on-task effect. Although sAA showed no significant group-level change (BF₁₀ = 0.25, indicating evidence for the null hypothesis), individual differences in the change in sAA (post–pre) were evident. Task accuracy and the change in sAA were associated with subjective measures of mood and stress. These findings suggest that cognitive stress is reflected differently across pupil area, changes in sAA, and subjective measures, highlighting the value of integrating multiple physiological and psychological indicators. Full article

Background/Objectives: Primary Sjögren’s disease is a systemic autoimmune disease characterized by chronic inflammation of exocrine glands and heterogeneous clinical manifestations. There remains a need for objective, non-invasive biomarkers that reflect local glandular involvement and disease-related immune activity. Methods: This observational cross-sectional case–control study included 34 patients fulfilling the 2016 ACR/EULAR classification criteria for primary Sjögren’s disease and 34 healthy controls between December 2024 and February 2025. Unstimulated whole-saliva samples were collected in the morning using the passive drool method, and salivary galectin-9 concentrations were measured via the enzyme-linked immunosorbent assay. Disease activity and symptom burden were assessed using validated indices, and receiver operating characteristic analysis was performed to evaluate discriminatory performance. Results: Salivary galectin-9 levels were significantly higher in patients with primary Sjögren’s disease compared with healthy controls. However, no significant associations were observed between salivary galectin-9 levels and disease activity scores after correction for multiple comparisons, nor with patient-reported symptoms, autoantibody profiles, Schirmer test results, or minor salivary gland biopsy findings. Salivary galectin-9 demonstrated limited discriminative ability between patients and controls. Conclusions: Salivary galectin-9 levels were elevated in primary Sjögren’s disease and may be associated with local glandular immune processes. Further prospective studies are needed to determine their clinical relevance. Full article

Background: Oral dysbiosis during pregnancy has been associated with adverse outcomes, including preterm birth, premature rupture of membranes (PROM), and low birth weight, yet oral health remains an underappreciated component of routine prenatal care. Dental caries and gingival bleeding are frequently reported during pregnancy and may remain clinically relevant in the immediate postpartum period, but their relationship with specific oral pathogens in postpartum women has been insufficiently characterised, particularly in Eastern European populations. Methods: This exploratory cross-sectional, single-centre study included 60 postpartum women recruited consecutively at “Cuza-Vodă” Clinical Hospital of Obstetrics and Gynecology, Iași, Romania, between December 2025 and February 2026. All participants completed a structured questionnaire covering obstetric history, demographic characteristics, and oral hygiene behaviours and underwent a standardised clinical oral examination by two calibrated examiners. Before study initiation, the two examiners underwent a joint calibration session based on the predefined visual oral assessment criteria used in this study and agreed on uniform recording procedures for visible dental caries, self-reported gingival bleeding during brushing, tooth mobility, and overall oral status. Saliva samples were collected after delivery. Genomic DNA was extracted using a magnetic-bead protocol and analysed by Real-Time PCR using TaqMan-based assays to detect four oral pathogens: Porphyromonas gingivalis, Streptococcus mutans, Mycoplasma salivarium, and Fusobacterium nucleatum. Results: Most participants were primiparous (55.0%) and delivered at term (≥37 weeks of gestation; 78.3%). The prevalence of pathogen detection was: P. gingivalis 38.3% (23/60), S. mutans 70.0% (42/60), M. salivarium 71.7% (43/60), and F. nucleatum 100% (60/60). Poly-microbial carriage was common: 15.0% of participants carried all three variable pathogens simultaneously (S. mutans, M. salivarium, and P. gingivalis), and the most frequent two-pathogen combination was S. mutans + M. salivarium (30.0%). No statistically significant associations were identified between pathogen detection and clinical or obstetric variables, consistent with limited statistical power in this small convenience sample. Conclusions: This exploratory study provides the first salivary prevalence estimates for these four oral pathogens in postpartum women in Northeast Romania. The high prevalence of poly-microbial carriage, including the novel quantitative estimate for M. salivarium, provides an empirical foundation for power calculations and future confirmatory research integrating standardised periodontal assessment with pregnancy outcome data. Full article

Background: Cesarean delivery is commonly performed under either spinal or general anesthesia. While both techniques are widely used, their differential effects on maternal neurochemical profiles, particularly excitatory neurotransmitters such as glutamate, remain incompletely understood. Glutamate plays a central role in stress response, nociception, and neuroendocrine regulation. This study aimed to compare maternal salivary glutamate concentrations between spinal and general anesthesia during cesarean delivery. Method: In this prospective study, 66 women undergoing cesarean delivery were included: 32 received spinal anesthesia and 34 received general anesthesia. Unstimulated saliva samples were collected perioperatively and analyzed using a colorimetric enzymatic assay. Clinical and demographic variables were extracted from electronic medical records. Results: Baseline maternal and neonatal characteristics were comparable between groups (all p > 0.05). Glutamate concentrations were not normally distributed. Median salivary glutamate levels were significantly higher in the general anesthesia group compared with the spinal anesthesia group (8.05 nmol/µL [IQR 4.81–11.69] vs. 5.19 nmol/µL [IQR 3.05–8.39]; p = 0.041) After adjustment for maternal and perinatal covariates, anesthesia type was not independently associated with glutamate levels (p = 0.21). Conclusion: General anesthesia was associated with higher unadjusted maternal salivary glutamate levels compared with spinal anesthesia during cesarean delivery; however, this association did not persist after multivariable adjustment. These findings suggest that anesthesia technique alone may not independently influence perioperative glutamatergic responses. Further research is warranted to clarify the clinical significance of these neurochemical changes for maternal and neonatal outcomes. Full article