Xerostomia in a Group of Turkish Patients Using an Online Survey During the COVID-19 Pandemic.

Background Xerostomia is defined as the subjective feeling of dry mouth and affects millions of patients worldwide. Most studies are based on samples of the elderly in nursing homes. This study aimed to investigate the presence of xerostomia and the severity of self-reported xerostomia by sociodemographic variables and to evaluate xerostomia symptoms (self-reported halitosis, burning mouth, and mouth sores) in young adults. Methodology A questionnaire regarding sociodemographic data and the 11-item Xerostomia Inventory was delivered to patients aged 20-65 years who applied to the Ankara University Faculty of Dentistry for dental treatment before the COVID-19 pandemic. Statistical analyses were performed to determine the relationships between the presence of xerostomia and other variables such as age, gender, the presence of a systemic disease, medication use, smoking, alcohol consumption, and the use of removable prostheses. Results A total of 300 patients were included in the study. Xerostomia presence of 54.6% (164 patients) was identified. A significant relationship was found between age and xerostomia (p = 0.023; p = 0.001). The presence of xerostomia decreased as age increased. Xerostomia was more common in female patients (p = 0.028; p = 0.004). The presence of xerostomia was found to be high, not only in the elderly but also in younger adults. Conclusions This study sheds light on the current status, symptoms, and etiology of xerostomia presence in the young population in Turkey. Factors associated with xerostomia were age, female gender, and the number of cigarettes smoked per day. In this study, the high presence of xerostomia was due to smoking.

Wharton's jelly mesenchymal stem cells: Future regenerative medicine for clinical applications in mitigation of radiation injury.

Wharton's jelly mesenchymal stem cells (WJ-MSCs) are gaining significant attention in regenerative medicine for their potential to treat degenerative diseases and mitigate radiation injuries. WJ-MSCs are more naïve and have a better safety profile, making them suitable for both autologous and allogeneic transplantations. This review highlights the regenerative potential of WJ-MSCs and their clinical applications in mitigating various types of radiation injuries. In this review, we will also describe why WJ-MSCs will become one of the most probable stem cells for future regenerative medicine along with a balanced view on their strengths and weaknesses. Finally, the most updated literature related to both preclinical and clinical usage of WJ-MSCs for their potential application in the regeneration of tissues and organs will also be compiled.

Effect of dose to parotid ducts on Sticky Saliva and Xerostomia in radiotherapy of head and neck squamous cell carcinoma.

BACKGROUND: Radiotherapy (RT) in head and neck squamous cell cancer (HNSCC) often leads to sticky saliva and xerostomia (SSX). Dose sparing of salivary glands (SG) reduces occurrence of SSX but few studies investigated the relationship between RT dose to SG substructures and SSX. We therefore investigated this hypothesis, focusing on the parotid duct (PD). METHODS: Retrospective data was collected from 99 HNSCC patients treated at our center with (chemo-)radiotherapy (CRT). PD and other organs-at-risk (OAR) were (re-)contoured and DVHs were generated without re-planning. SSX was graded according to CTCAE v.4.03 and evaluated at acute, subacute, and two late timepoints. RESULTS: Most patients presented with loco-regionally advanced disease. In 47% of patients, up-front neck dissection preceded CRT. Weighted mean dose was 28.6 Gy for bilateral parotid glands (PG), and 32.0 Gy for PD. Acute SSX presented as grades 0 (35.3%), I (41.4%), II (21.2%) and III (2.0%). There was no association of OARs and SSX ≥ grade 2 in univariable logistic regression (LR). Multivariable LR showed statistically significant relationship of acute SSX with: PG weighted mean dose (OR 0.84, p = 0.004), contralateral PG mean dose (OR 1.14, p = 0.02) and contralateral PD planning OAR (PD PRV) mean dose (OR 1.84, p = 0.03). CONCLUSIONS: There was an association of acute SSX with dose exposure of PD PRV in multivariable regression, only. Due to statistical uncertainties and the retrospective nature of this analysis, further studies are required to confirm or reject the hypothesis.

Application of enhanced recovery after surgery for oral dryness prevention after endoscopic sinus surgery.

OBJECTIVE: To investigate the efficacy of cluster nursing intervention based on Enhanced Recovery After Surgery (ERAS) for xerostomia in chronic rhinosinusitis after nasal endoscopic surgery. METHODS: A total of 80 patients with chronic rhinosinusitis who underwent functional nasal endoscopic surgery between January 2020 and December 2021 were selected and randomly divided into a control group (n = 40) and an experimental group (n = 40). Patients in the control group were treated with general nursing, while ERAS-based cluster nursing intervention was adopted for the experimental group, in addition to general nursing. Xerostomia stage and comfort level were observed at 2 h, 6 h, 24 h and 48 h after surgery; negative emotions before and after nursing were also observed. RESULTS: After the intervention, the xerostomia stage and comfort level at 6, 24 and 48 after surgery were higher in the experimental group (p < 0.05). Negative emotions in the experimental group were lower after nursing (p < 0.001). The self-rating depression scale and self-rating anxiety scale scores increased after nursing in both two groups (p < 0.05). CONCLUSION: Enhanced recovery after surgery-based cluster nursing intervention can alleviate xerostomia, improve patients' comfort levels, reduce their negative emotions and accelerate postoperative recovery.

Decellularization of Rat Submandibular Gland for Salivary Gland Tissue-Engineering Applications.

OBJECTIVES: This study describes a robust and versatile method for decellularization of rat submandibular glands (SMGs). METHODS: Briefly, rat SMGs were harvested and subjected to perfusion cycles using an anionic detergent. Native and decellularized SMG tissues were subjected to histological analysis using hematoxylin and eosin (H&E) stain and immunohistochemical staining using Hoescht reagent. Further, complementary DNA was synthesized using the native and decellularized SMG tissues and subjected to quantitative reverse transcription polymerase chain reaction (RT-PCR) using rat-specific genes (i.e., α-amylase [Amyl], aquaporin 5 [Aqp5], mucin 19 [Muc19] and glyceraldehyde-3-phosphate dehydrogenase [GAPDH]). The total DNA within native and decellularized SMG tissues were also quantified. RESULTS: H&E staining of SMG tissues revealed preserved ECM content. Decellularized SMG scaffolds lacked cellular material but retained collagen bundles similar to native SMGs. Hoechst reagent immunostaining showed cell nuclei and DNA present in native SMG but not in decellularized SMG scaffolds. Quantitative RT-PCR analysis showed specific amplification products of salivary gland-specific genes (Amyl, Muc19 and Aqp5) and GAPDH in the native SMG tissues. However, no amplification product was observed in the cDNAs from the decellularized SMG scaffolds, confirming the absence of DNA. Quantification of the DNA content showed that the decellularized SMG scaffolds had significantly lower DNA content than native SMG tissue. CONCLUSIONS: Results from this study demonstrated that the decellularization protocol was effective in removing cellular material while preserving the extracellular matrix components and structural integrity of the native SMG tissue.

The Mechanism of 540 nm Green Light in Promoting Salivary Secretion.

Background: Although low-level laser therapy (LLLT) is a widely used noninvasive treatment because of photobiomodulation effects, its application for xerostomia remained uncertain. Tight junctions (TJs), mainly composed of claudins, occludin, and ZO family members, are crucial structures that determine material transport through paracellular pathway in salivary gland epithelial cells. This work aimed to investigate whether LLLT affected salivary secretion through epithelial TJs. Methods: Transepithelial electrical resistance (TER) measurement and paracellular permeability assay were applied to evaluate paracellular permeability in submandibular gland (SMG)-C6 cells after irradiation with 540 nm green light. Immunofluorescence and western blot were used to detect the expression of TJ proteins. Quantitative phosphoproteomics were performed to explore possible intracellular signals. Results: We found that irradiation with 540 nm green light significantly decreased TER values while increased paracellular transport in SMG-C6 cells. 540 nm green light-induced redistribution of claudin-1, -3, and -4, but not occludin or ZO-1. Moreover, above phenomena were abolished by preincubation with capsazepine, an antagonist of transient receptor potential vanilloid subtype 1. Notably, irradiation with 540 nm green light on the skin covering the whole submandibular gland regions promoted salivary secretion and attenuated lymphocytic infiltration in 21-week-old non-obese diabetic mice (n = 5 per group), a xerostomia animal model for Sjögren's syndrome. Through in-depth bioinformatics analysis and expression verification, ERK1/2 and EphA2 served as potential canonical and noncanonical signals underlying 540 nm green light. Conclusions: Our findings uncovered the novel therapeutic effects of 540 nm green light on xerostomia through regulation on the expression and distribution of TJs.

Scent of relief: Mastic resin scent recovers salivation in chronic dry mouth patients.

BACKGROUND: Olfactory stimulation with mastic resin, derived from the Pistacia lentiscus tree, demonstrated a bona fide sialagogic effect in healthy volunteers [1]. Its main volatile compound, α-pinene, also showed this effect. The current study aimed to validate the effect of mastic resin volatiles in chronic dry mouth patients with confirmed decreased saliva secretion. METHODS: 41 chronic dry mouth patients with decreased unstimulated saliva secretion (<0.25 mL/min) were exposed to mastic resin volatiles as part of the diagnostic routine at the Saliva Clinic of Academic Centre for Dentistry Amsterdam. During their visit, dry-mouth questionnaires were conducted and samples of unstimulated whole saliva, chew-stimulated saliva, acid-stimulated saliva and mastic resin stimulated saliva were collected. Saliva flow rate, spinnbarkeit, pH, ion composition, MUC5B and MUC7 levels in all samples were analyzed. RESULTS: Salivary flow rates increased by all stimuli when compared to the baseline unstimulated saliva (P<0.001). During olfactory mastic resin stimulation, the salivary spinnbarkeit (P<0.001) and sodium concentration (P<0.01) were increased compared to unstimulated saliva. MUC5B and MUC7 levels were increased during olfactory mastic resin stimulation compared to chew-stimulated saliva (P=0.016 and P<0.001, respectively). Spinnbarkeit correlated positively with MUC5B (R=0.399, P=0.002) and MUC7 levels (R=0.375, P=0.004). Results of dry-mouth questionnaires indicated reduced posterior palate dryness shortly after olfactory mastic resin stimulation (P=0.04). CONCLUSIONS: Olfactory mastic resin stimulation increased mucous saliva secretion and reduced posterior palate dryness in a group of chronic dry mouth patients. These findings, validated in patients, underscore mastic resin scent as a beneficial and non-invasive sialagogic treatment for clinical applications.

The impact of alternate-day fasting on the salivary gland stem cell compartments in non-obese diabetic mice with newly established Sjögren's syndrome.

Intermittent fasting exerts a profound beneficial influence on a spectrum of diseases through various mechanisms including regulation of immune responses, elimination of senescent- and pathogenic cells and improvement of stem cell-based tissue regeneration in a disease- and tissue-dependent manner. Our previous study demonstrated that alternate-day fasting (ADF) led to alleviation of xerostomia and sialadenitis in non-obese diabetic (NOD) mice, a well-defined model of Sjögren's syndrome (SS). This present study delved into the previously unexplored impacts of ADF in this disease setting and revealed that ADF increases the proportion of salivary gland stem cells (SGSCs), defined as the EpCAMhi cell population among the lineage marker negative submandibular gland (SMG) cells. Furthermore, ADF downregulated the expression of p16INK4a, a cellular senescence marker, which was concomitant with increased apoptosis and decreased expression and activity of NLRP3 inflammasomes in the SMGs, particularly in the SGSC-residing ductal compartments. RNA-sequencing analysis of purified SGSCs from NOD mice revealed that the significantly downregulated genes by ADF were mainly associated with sugar metabolism, amino acid biosynthetic process and MAPK signaling pathway, whereas the significantly upregulated genes related to fatty acid metabolic processes, among others. Collectively, these findings indicate that ADF increases the SGSC proportion, accompanied by a modulation of the SGSC property and a switch from sugar- to fatty acid-based metabolism. These findings lay the foundation for further investigation into the functionality of SGSCs influenced by ADF and shed light on the cellular and molecular mechanisms by which ADF exerts beneficial actions on salivary gland restoration in SS.

Thirst in adult patients in the intensive care unit: A scoping review.

PURPOSE: To review the literature on thirst in intensive care unit (ICU) patients and report potential causes, risk factors, diagnosis and measurement tools, as well as potential co-occurrence with other distressing symptoms, and the management of thirst in the ICU. DESIGN: A scoping review employing the Joanna Briggs Institute methodology. METHODS: PubMed, MEDLINE, EMBASE and CINAHL were searched from inception to April 2024. Any type of empirical study reporting thirst or associated xerostomia in adult patients (≥18 years) admitted to an ICU or high dependency unit for more than 24 h were included. RESULTS: The search yielded 907 unique records, and after evaluating 65 full-text publications, 21 studies were included. Thirst intensity was addressed most often (eleven studies), whereas the experience (or quality) of thirst and the validation of a measurement instrument, were addressed in only one study. Although co-occurrence of symptoms was addressed in four studies, only one pilot study looked into the interaction of thirst with other symptoms. Intervention studies have been focussing primarily on mouth-care interventions. CONCLUSION: Thirst is a distressing symptom in the ICU, with reported high prevalence and intensity. Knowledge about its causes, interventions that incorporate minimising its risk, occurrence and intensity are limited. IMPLICATIONS FOR CLINICAL PRACTICE: Health care providers should acknowledge thirst as a prominent symptom for ICU patients. They should possess knowledge on the factors that potentially evoke or aggravate thirst. Regular and timely relief of thirst by oral care with cold swabs and the application of menthol can be regarded as a first choice of intervention.

Salivary gland organoid transplantation as a therapeutic option for radiation-induced xerostomia.

BACKGROUND: Xerostomia is a pathological condition characterized by decreased salivation due to salivary gland dysfunction and is frequently attributed to irreversible damage as a side effect of radiation therapy. Stem cell-derived organoid therapy has garnered attention as a promising avenue for resolving this issue. However, Matrigel, a hydrogel commonly used in organoid culture, is considered inappropriate for clinical use due to its undefined composition and immunogenicity. In this study, we aimed to develop a method for culturing collagen-based human salivary gland organoids (hSGOs) suitable for clinical applications and evaluated their therapeutic effectiveness. METHODS: Human salivary gland stem cells were isolated from the salivary gland tissues and cultured in both Matrigel and collagen. We compared the gene and protein expression patterns of salivary gland-specific markers and measured amylase activity in the two types of hSGOs. To evaluate the therapeutic effects, we performed xenogeneic and allogeneic transplantation using human and mouse salivary gland organoids (hSGOs and mSGOs), respectively, in a mouse model of radiation-induced xerostomia. RESULTS: hSGOs cultured in Matrigel exhibited self-renewal capacity and differentiated into acinar and ductal cell lineages. In collagen, they maintained a comparable self-renewal ability and more closely replicated the characteristics of salivary gland tissue following differentiation. Upon xenotransplantation of collagen-based hSGOs, we observed engraftment, which was verified by detecting human-specific nucleoli and E-cadherin expression. The expression of mucins, especially MUC5B, within the transplanted hSGOs suggested a potential improvement in the salivary composition. Moreover, the allograft procedure using mSGOs led to increased salivation, validating the efficacy of our approach. CONCLUSIONS: This study showed that collagen-based hSGOs can be used appropriately in clinical settings and demonstrated the effectiveness of an allograft procedure. Our research has laid the groundwork for the future application of collagen-based hSGOs in allogeneic clinical trials.

Correlations between Obstructive Sleep Apnea Syndrome and Periodontitis: A Systematic Review and Meta-Analysis.

The focus of this article was to evaluate the link between obstructive sleep apnea syndrome (OSAS) and periodontitis, considering various hypotheses supporting the relationship between respiratory disorders and periodontitis. The literature review for this study was performed using the PubMed, Google Scholar, Cochrane library, and Proquest databases. The review process was guided by the PRISMA guidelines. The PECOS protocol (Population, Exposure, Control, Outcome, Study) was followed in developing the search strategy to ensure consistent and accurate selection of articles. To evaluate quality, cross-sectional studies were reviewed using the Joanna Briggs Institute (JBI) critical appraisal tool. Case-control studies were assessed with the Newcastle-Ottawa Scale (NOS). The research included a total of 10 studies, encompassing 88,040 participants. The meta-analysis observed a statistically significant association between OSAS and periodontitis, with an odds ratio OR = 2.4620 (95%-CI: 1.7345-3.4946 p ≤ 0.0001). The results suggest a potential association between OSA and periodontitis. Further investigations are warranted to confirm this association and elucidate its underlying mechanism.

Oral discomfort and health behavior of patients with typical vs. atypical antipsychotic drugs.

Introduction: Psychiatric patients suffer from oral diseases and side effects of antipsychotic medication. In particular, the typical antipsychotic drugs may cause severe hyposalivation with subsequent oral symptoms. We therefore aimed to compare oral health behavior and oral side effects of in-hospital patients taking typical vs. atypical antipsychotic drugs with the hypothesis that the former drugs cause more oral pain than the newer drugs. Methods: This cross-sectional questionnaire and interview study investigated subjective oral symptoms and their health behavior in 170 hospitalized psychiatric patients, comparing those taking typical vs. atypical antipsychotic drugs. Cross-tabulations and chi-square tests were used for analyses. Results: Persistent oral pain lasting throughout the day was reported by 46% in the typical, and 5% in the atypical antipsychotic group patients, respectively. In both groups, the pain was mainly in the tongue and buccal mucosa and was described as a burning sensation. A significantly higher prevalence of xerostomia was reported in the typical antipsychotic medication group (66%) compared with the atypical antipsychotic medication group (53%, p<0.01). Self-assessed dental health was assessed as poor by two-thirds of the patients of whom 69% reported toothbrushing once daily. Approximately half of them reported having had a visit to a dentist within the previous year. Of the women 28%, and of the men 17%, respectively, had received professional consultations for oral symptoms. Conclusion: The current results on psychiatrically hospitalized patients emphasize the need for awareness of oral discomfort and its subsequent effects on the quality of life in this challenging patient group. Focus should also be placed on a wide range of support encouraging the patients to maintain good daily oral hygiene and seek professional dental help when needed.

Diagnosis and Dental Management of a Patient With Forbes Albright Syndrome: A Report of a Rare Case.

Forbes Albright syndrome is a hyperprolactinemia syndrome linked to a pituitary tumor associated with galactorrhea and amenorrhea. Cabergoline, an ergot derivative, is its drug of choice. Here, we report the oral manifestations and management of a case of a 32-year-old female, diagnosed and treated with the same. The patient had an alarming increase in the incidence and progression of dental caries. Her diagnosis and management have been highlighted. This can have overbearing effects on the psychology and function of the individual, thus making early diagnosis and precise management important.

Endogenous IL-22 contributes to the pathogenesis of salivary gland dysfunction in the non-obese diabetic model of Sjögren's syndrome.

SjÓ§gren's syndrome is a systemic autoimmune disease primarily targeting the salivary and lacrimal glands. Our previous investigations have shown that administration of interleukin-22 (IL-22), an IL-10 family cytokine known for its complex and context-dependent effects on tissues, either protective- or detrimental, to salivary glands leads to hypofunction and pathological changes of salivary glands in C57BL/6 mice and in non-obese diabetic (NOD) mice, the latter being a commonly used model of SjÓ§gren's syndrome. This study aims to delineate the pathophysiological roles of endogenously produced IL-22 in the development of salivary gland pathologies and dysfunction associated with SjÓ§gren's disease in the NOD mouse model. Our results reveal that neutralizing IL-22 offered a protective effect on salivary gland function without significantly affecting the immune cell infiltration of salivary glands or the autoantibody production. Blockade of IL-22 reduced the levels of phosphorylated STAT3 in salivary gland tissues of NOD mice, while its administration to salivary glands had the opposite effect. Correspondingly, the detrimental impact of exogenously applied IL-22 on salivary glands was almost completely abrogated by a specific STAT3 inhibitor. Moreover, IL-22 blockade led to a downregulation of protein amounts of Ten-Eleven-Translocation 2, a methylcytosine dioxygenase critical for mediating interferon-induced responses, in salivary gland epithelial cells. IL-22 neutralization also exerted a protective effect on the salivary gland epithelial cells that express high levels of surface EpCAM and bear the stem cell potential, and IL-22 treatment in vitro hampered the survival/expansion of these salivary gland stem cells, indicating a direct negative impact of IL-22 on these cells. In summary, this study has uncovered a critical pathogenic role of the endogenous IL-22 in the pathogenesis of Sjögren's disease-characteristic salivary gland dysfunction and provided initial evidence that this effect is dependent on STAT3 activation and potentially achieved through fostering Tet2-mediated interferon responses in salivary gland epithelial cells and negatively affecting the EpCAMhigh salivary gland stem cells.

MASCC/ISOO Clinical Practice Statement: Clinical assessment of salivary gland hypofunction and xerostomia in cancer patients.

PURPOSE: A MASCC/ISOO Clinical Practice Statement (CPS) is aimed at generating a concise tool for clinicians that concentrates practical information needed for the management of oral complications of cancer patients. This CPS is focused on the clinical assessment of salivary gland hypofunction and xerostomia in cancer patients. METHODS: This CPS was developed based on a critical evaluation of the literature followed by a structured discussion of a group of leading experts, members of the Oral Care Study Group of MASCC/ISOO. The information is presented in the form of succinct bullets and tables to generate a short manual about the best standard of care. RESULTS: The objective assessment of saliva secretion involves an extra- and intra-oral clinical examination while the subjective assessment involves eliciting information on the patient's complaint of xerostomia and its impact on daily functioning. This CPS summarizes the common investigator- and patient-reported instruments used in clinical practice for assessing salivary gland hypofunction and xerostomia in cancer patients. CONCLUSION: There is a range of tools to assess salivary gland function in patients undergoing cancer therapy, patients recovering from cancer therapy, or cancer survivors. Clinicians should ideally conduct both objective and subjective measurements to ensure a clear understanding about the status of the patients in order to provide the most appropriate treatment.

MASCC/ISOO Clinical Practice Statement: Management of salivary gland hypofunction and xerostomia in cancer patients.

PURPOSE: A MASCC/ISOO Clinical Practice Statement (CPS) is aimed at generating a concise tool for clinicians that concentrates practical information needed for the management of oral complications of cancer patients. This CPS is focused on the management of salivary gland hypofunction and xerostomia in cancer patients. METHODS: This CPS was developed based on critical evaluation of the literature followed by a structured discussion of a group of leading experts, members of the Oral Care Study Group of MASCC/ISOO. The information is presented in the form of succinct bullets and tables to generate a short manual about the best standard of care. RESULTS: Salivary gland hypofunction and xerostomia in cancer patients are managed by (i) stimulating saliva production of salivary glands with residual secretory capacity or (ii) artificial wetting of the oral and lip surfaces which can be achieved by pharmacological or non-pharmacological interventions. Pharmacological interventions encompass the use of sialagogues and sialolytics, while non-pharmacological interventions involve the use of moistening agents, mechanical, gustatory, or electrostimulation of the salivary glands. Additional treatment modalities may be incorporated in practice based on local availability and the clinician's experience. CONCLUSION: The information presented in this CPS offers clinicians convenient access to the dosages and regimens of different interventions for managing salivary gland hypofunction or xerostomia to facilitate clinical efficiency and conserve valuable time for clinicians.

Efficacy of Lemon Mouthwash in Improving Dry Mouth Symptoms and Salivary Flow in Hemodialysis Patients.

OBJECTIVES: Gargling mouthwash is a safe and convenient oral care intervention; it rinses the mouth and increases salivary flow rate. The effectiveness of lemon mouthwash in relieving xerostomia and increasing the salivary flow rate among hemodialysis patients has not been studied. Our study sought to analyze the effectiveness of varying concentrations of lemon in mouthwash solutions on xerostomia and salivary flow rate. METHODS: A multi-concentration test was used to assess lemon mouthwash at 20%, 15%, 10%, 5%, and 2.5% concentrations to determine the optimal concentration for relieving dry mouth and increasing salivary flow rate. Generalized estimating equations were used to analyze the differences between various concentrations of lemon mouthwash and baseline values. RESULTS: In total, 44 patients were recruited. The 10% lemon concentration mouthwash was the most effective for increasing salivary flow rate, but the 5% and 2.5% were better accepted by the participants. Our findings can help establish intervention guidelines to relieve xerostomia among hemodialysis patients. CONCLUSION: Our findings can help establish intervention guidelines to relieve xerostomia among hemodialysis patients.

PIEZO1 activation may serve as an early tissue biomarker for the prediction of irradiation-induced salivary gland dysfunction.

Irradiation (IR)-induced xerostomia is the most common side effect of radiation therapy in patients with head and neck cancer (HNC). Xerostomia diagnosis is mainly based on the patient's medical history and symptoms. Currently, no direct biomarkers are available for the early prediction of IR-induced xerostomia. Here, we identified PIEZO1 as a novel predictive tissue biomarker for xerostomia. Our data demonstrate that PIEZO1 is significantly upregulated at the gene and protein levels during IR-induced salivary gland (SG) hypofunction. Notably, PIEZO1 upregulation coincided with that of inflammatory (F4/80) and fibrotic markers (fibronectin and collagen fibers accumulation). These findings suggest that PIEZO1 upregulation in SG tissue may serve as a novel predictive marker for IR-induced xerostomia.

Validation of quantitative magnetic resonance imaging techniques in head and neck healthy structures involved in the salivary and swallowing function: Accuracy and repeatability.

Background and Purpose: Radiation-induced damage to the organs at risk (OARs) in head-and-neck cancer (HNC) patient can result in long-term complications. Quantitative magnetic resonance imaging (qMRI) techniques such as diffusion-weighted imaging (DWI), DIXON for fat fraction (FF) estimation and T2 mapping could potentially provide a spatial assessment of such damage. The goal of this study is to validate these qMRI techniques in terms of accuracy in phantoms and repeatability in-vivo across a broad selection of healthy OARs in the HN region. Materials and Methods: Scanning was performed at a 3 T diagnostic MRI scanner, including the calculation of apparent diffusion coefficient (ADC) from DWI, FF and T2 maps. Phantoms were scanned to estimate the qMRI techniques bias using Bland-Altman statistics. Twenty-six healthy subjects were scanned twice in a test-retest study to determine repeatability. Repeatability coefficients (RC) were calculated for the parotid, submandibular, sublingual and tubarial salivary glands, oral cavity, pharyngeal constrictor muscle and brainstem. Additionally, a linear mixed-effect model analysis was used to evaluate the effect of subject-specific characteristics on the qMRI values. Results: Bias was 0.009x10-3 mm2/s for ADC, -0.7 % for FF and -7.9 ms for T2. RCs ranged 0.11-0.25x10-3 mm2/s for ADC, 1.2-6.3 % for FF and 2.5-6.3 ms for T2. A significant positive linear relationship between age and the FF and T2 for some of the OARs was found. Conclusion: These qMRI techniques are feasible, accurate and repeatable, which is promising for treatment response monitoring and/or differentiating between healthy and unhealthy tissues due to radiation-induced damage in HNC patients.