Search

Background: Hyposalivation is treated using oral cholinergic drugs; however, systemic side effects occasionally lead to discontinuation of treatment. We aimed to investigate the effects of transdermal pilocarpine on the salivary gland skin on saliva secretion and safety in rats. Methods: Pilocarpine was administered to rats orally (0.5 mg/kg) or topically on the salivary gland skin (5 mg/body). Saliva volume, the number of sweat dots, and fecal weight were measured along with pilocarpine concentration in plasma and submandibular gland tissues. Results: Saliva volume significantly increased 0.5 h after oral administration and 0.5, 3, and 12 h after topical administration. Fecal weight and sweat dots increased significantly 1 h after oral administration; however, no changes were observed after topical application. The pilocarpine concentration in the submandibular gland tissues of the topical group was higher than that in the oral group at 0.5, 3, and 12 h of administration. Conclusions: Pilocarpine application to salivary gland skin persistently increased salivary volume in rats without inducing sweating or diarrhea. Transdermal pilocarpine applied to the skin over the salivary glands may be an effective and safe treatment option for hyposalivation. [ABSTRACT FROM AUTHOR]

Background and Objectives: Tonsillitis is common in children and is predominantly caused by viruses and, less frequently, by bacteria such as group A beta-hemolytic streptococcus. The treatment primarily involves supportive care; however, the overuse of antibiotics remains a concern due to rising antibiotic resistance. Probiotics, particularly Lactobacillus strains, have been shown to modulate immune responses, offering a potential alternative treatment. Materials and Methods: Our prospective single-arm, open-label study included 98 pediatric patients aged 5–15 years with recurrent throat and tonsil infections, from October 2022 to January 2023. Patients received lozenges containing heat-killed Lactobacillus helveticus MIMLh5. Monthly follow-ups involved a comprehensive ear, nose, and throat examination, throat cultures, and recording the frequency of infections and antibiotic use. Data were analyzed using SPSS 29.0, with statistical significance set at p < 0.05. Results: After three months, significant reductions were observed in the occurrences of nose and throat infections (p < 0.001), enlarged submandibular glands (p < 0.001), and positive throat cultures (p < 0.001). Antibiotic and corticosteroid prescriptions also significantly decreased (p < 0.001). Among children aged 5–10 years, significant improvements were noted in throat and tonsil infections (p < 0.001) and positive throat cultures (p = 0.012). Overall, there was a substantial reduction in school days missed (p < 0.001). Conclusions: The use of paraprobiotic Lactobacillus helveticus MIMLh5 lozenges significantly reduced the incidence of recurrent throat and tonsil infections in children, decreased the need for antibiotics and corticosteroids, and improved overall clinical outcomes without adverse effects. These findings support the use of paraprobiotic supplements as a safe and effective preventive measure for pediatric throat and tonsil infections. [ABSTRACT FROM AUTHOR]

This article explores the use of 18F-choline-PET/CT imaging for non-FDG-avid salivary gland cancer. Salivary gland tumors are rare and have diverse characteristics. While cross-sectional imaging with contrast-enhanced CT or MRI is the standard for initial staging, FDG-PET has also been used. However, some tumors do not show high FDG uptake, so the study aimed to assess the potential of the non-FDG tracer 18F-choline. The study included five patients with malignant salivary gland tumors and found promising results. Choline-PET was found to be somewhat superior to FDG-PET for salivary gland cancer, especially for low-grade tumors and adenoid cystic carcinoma. However, the high background uptake of choline affected the evaluation of the primary tumor. The authors concluded that more specific radiopharmaceuticals are needed for certain types of primary salivary gland carcinoma. [Extracted from the article]

Background: Internal dosimetry in individual patients is essential for safe and effective radioligand therapy. Multiple time point imaging for accurate dosimetry is time consuming and hence can be demanding for nuclear medicine departments as well as patients. The objectives of this study were (1) to assess absorbed doses to organs at risk and tumor lesions for [177Lu]Lu-PSMA-I&T using whole body SPECT imaging and (2) to investigate possible simplified dosimetry protocols. Methods: This study included 16 patients each treated with 4 cycles of [177Lu]Lu-PSMA-I&T. They underwent quantitative whole body SPECT/CT imaging (3 bed positions) at four time points (TP) comprising 2 h, 24 h, 48 h and 72–168 h post-injection (p.i.). Full 3D dosimetry (reference method) was performed for all patients and dose cycles for organs at risk (kidneys, parotid glands and submandibular glands) and up to ten tumor lesions per patient (resulting in 90 lesions overall). The simplified dosimetry methods (SM) included (1) generating time activity curves for subsequent cycles using a single TP of imaging applying the kinetics of dose cycle 1, and for organs at risk also (2) simple extrapolation from dose cycle 1 and (3) from both, dose cycle 1 and 2. Results: Normalized absorbed doses were 0.71 ± 0.32 mGy/MBq, 0.28 ± 0.12 mGy/MBq and 0.22 ± 0.08 mGy/MBq for kidneys, parotid glands and submandibular glands, respectively. Tumor doses decreased from 3.86 ± 3.38 mGy/MBq in dose cycle 1 to 2.01 ± 2.65 mGy/MBq in dose cycle 4. Compared to the full dosimetry approach the SM 1 using single TP imaging at 48 h p.i. resulted in the most accurate and precise results for the organs at risk in terms of absorbed doses per cycle and total cumulated dose. For tumor lesions better results were achieved using the fourth TP (≥ 72 h p.i.). Conclusion: Simplification of safety dosimetry protocols is possible for [177Lu]Lu-PSMA-I&T therapy. If tumor dosimetry is of interest a later imaging TP (≥ 72 h p.i.) should be used/added to account for the slower kinetics of tumors compared to organs at risk. [ABSTRACT FROM AUTHOR]

Venom production has evolved independently many times in the animal kingdom, although it is rare among mammals. Venomous shrews produce venom in their submandibular salivary glands and use it for food acquisition. Only a few toxins have been identified in shrew venoms thus far, and their modes of action require investigation. The biological and molecular processes relating to venom production and gland functioning also remain unknown. To address this gap, we investigated protein content in extracts from venom glands of two shrew species, Neomys fodiens and Sorex araneus, and interpreted their biological functions. Applying a proteomic approach coupled with Gene Ontology enrichment analysis, we identified 313 and 187 putative proteins in venom glands of N. fodiens and S. araneus, respectively. A search of the UniProt database revealed that most of the proteins found in both shrew species were involved in metabolic processes and stress response, while GO enrichment analysis revealed more stress-related proteins in the glands of S. araneus. Molecules that regulate molecule synthesis, cell cycles, and cell divisions are necessary to enable venom regeneration and ensure its effectiveness in predation and food hoarding. The presence of proteins involved in stress response may be the result of shrews' high metabolic rate and the costs of venom replenishment. Some proteins are likely to promote toxin spreading during envenomation and, due to their proteolytic action, reinforce venom toxicity. Finally, finding numerous proteins involved in immune response suggests a potential role of shrew venom gland secretions in protection against pathogens. These findings open up new perspectives for studying biological functions of molecules from shrew venom glands and extend our knowledge on the functioning of eulipotyphlan venom systems. Because the majority of existing and putative venomous mammals use oral venom systems to inject venom into target species, the methods presented here provide a promising avenue for confirming or discovering new taxa of venomous mammals. [ABSTRACT FROM AUTHOR]

Copyright of Shipin Kexue/ Food Science is the property of Food Science Editorial Department and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Head and neck cancer (HNC) is the sixth most diagnosed cancer, and treatment typically consists of surgical removal of the tumor followed by ionizing radiation (IR). While excellent at controlling tumor growth, IR often damages salivary glands due to their proximity to common tumor sites. Radiation damage to salivary glands results in loss of secretory function, causing severe and chronic reductions in salivary flow. This leads to the patient-reported sensation of dry mouth, termed xerostomia, which significantly reduces quality of life for HNC patients and survivors. The mechanisms underlying salivary gland damage remain elusive, and therefore, treatment options are scarce. Available therapies provide temporary symptom relief, but there is no standard of care for permanent restoration of function. There is a significant gap in understanding the chronic mechanistic responses to radiation as well as treatments that can be given in the months to years following cessation of treatment. HNC cases are steadily rising; particularly, the number of young patients diagnosed with nonfatal human papillomavirus + HNC continues to increase. The growing number of HNC diagnoses and improved prognoses results in more people living with xerostomia, which highlights the mounting need for restorative treatments. Mechanisms underlying chronic damage include decreases in acinar differentiation markers, increases in acinar cell proliferation, immune and inflammatory dysregulation, and metabolic changes including increases in amino acids and reductions in glycolysis and oxidative phosphorylation, fibrosis, and dysregulated neuronal responses. Currently, promising treatment options include adenoviral gene transfers and stem cell therapy. Thus, this review describes in depth known mechanisms contributing to chronic damage and discusses therapeutic advances in treating chronically damaged glands. Understanding the chronic response to radiation offers potential in development of new therapeutics to reverse salivary gland damage and improve the quality of life of HNC survivors. [ABSTRACT FROM AUTHOR]

Warthin-like mucoepidermoid carcinoma (WL-MEC) is a newly reported variant of mucoepidermoid carcinoma. Its histological feature is easy to confused with metaplastic Warthin Tumor, and its relationship with Warthin tumor in histogenesis is controversial. In this study, we presented two cases of WLMEC, discussing their clinicopathological and molecular features. Notably, one case was initially misdiagnosed during the first onset of the tumor. Case 1 was a 60-year-old female with a mass in the right parotid gland. Case 2 featured a 29- year-old male who developed a lump at the original surgical site 6 months after a “Warthin tumor” resection from the submandibular gland. Histologically, both tumor exhibited a prominent lymphoid stroma and cystic pattern, accompanied by various amounts of epithelial nests composed of squamoid cells, intermediate cells and mucinous cells. The characteristic eosinophilic bilayer epithelium of Warthin tumor was not typically presented in either case. Both cases tested positive for MAML2 gene rearrangement. To contextualize our findings, we conducted a comprehensive review of forty-eight WL-MEC cases documented in the English literature, aiming to synthesizing a reliable differential diagnostic approach. WL-MEC is a rare yet clinically relevant variant, posing a diagnostic pitfall for pathologists. Our study underscores the importance of a meticulous evaluation of both clinical and histological features, coupled with the detection of MAML2 rearrangement, as a credible method for distinguishing WL-MEC from other benign and malignant lesions, particularly metaplastic Warthin tumor. [ABSTRACT FROM AUTHOR]

Introduction: Space is a unique environment characterized by isolation from community life and exposure to circadian misalignment, microgravity, and space radiation. These multiple differences from those experienced on the earth may cause systemic and local tissue stress. Autonomic nerves, including sympathetic and parasympathetic nerves, regulate functions in multiple organs. Saliva is secreted from the salivary gland, which is regulated by autonomic nerves, and plays several important roles in the oral cavity and digestive processes. The balance of the autonomic nervous system in the seromucous glands, such as the submandibular glands, precisely controls serous and mucous saliva. Psychological stress, radiation damage, and other triggers can cause an imbalance in salivary secretion systems. A previous study reported that amylase is a stress marker in behavioral medicine and space flight crews; however, the detailed mechanisms underlying amylase regulation in the space environment are still unknown. Methods: In this study, we aimed to elucidate how lunar gravity (1/6 g) changes mRNA expression patterns in the salivary gland. Using a multiple artificial gravity research system during space flight in the International Space Station, we studied the effects of two different gravitational levels, lunar and Earth gravity, on the submandibular glands of mice. All mice survived, returned to Earth from space, and their submandibular glands were collected 2 days after landing. Results: We found that lunar gravity induced the expression of the salivary amylase gene Amy1; however, no increase in Aqp5 and Ano1, which regulate water secretion, was observed. In addition, genes involved in the exocrine system, such as vesicle-associated membrane protein 8 (Vamp8) and small G proteins, including Rap1 and Rab families, were upregulated under lunar gravity. Conclusion: These results imply that lunar gravity upregulates salivary amylase secretion via Rap/Rab signaling and exocytosis via Vamp8. Our study highlights Amy1 as a potential candidate marker for stress regulation in salivary glands in the lunar gravity environment. [ABSTRACT FROM AUTHOR]

Mucocele or sialocele is characterized by the accumulation of saliva due to blockage of salivary flow, generally caused by trauma or inflammation. The present report aims to describe the surgical approach to mucocele in the submandibular salivary gland of a Lhasa Apso dog. This presented an increase in the mandibular region that was soft and painless. After confirmation of mucocele through imaging tests, it was decided to remove the affected salivary gland. After surgery, the patient recovered well, without complications, demonstrating that the surgical technique was effective. [ABSTRACT FROM AUTHOR]

Kimura disease (KD) is a rare benign chronic inflammatory disorder of unknown aetiology prevalence in young adult Asian males. Head and neck region especially salivary gland and cervical lymph node are the most commonly affected. In contrast to parotid gland, submandibular gland involvement is rarely reported. Diagnosis is always challenging due to variable presentations that may mimic other inflammatory or neoplastic conditions, and non-specific imaging, cytology, and histopathology findings. Generally, there was several treatments modality reported but showed variable response with high recurrence rate. The treatment for submandibular gland KD specifically is not well describe due to its rarity. We present a case of KD with submandibular gland and cervical lymph node involvement in elderly man that mimic malignancy and highlight the challenging in management. [ABSTRACT FROM AUTHOR]

This article presents a case report of a young woman with Sjögren's syndrome, an autoimmune disease affecting the salivary and lacrimal glands. The patient experienced swelling and pain in her parotid glands, which improved with short-term glucocorticoid treatment. The study suggests that salivary gland ultrasonography can be a valuable tool for monitoring treatment response and assessing disease activity in Sjögren's syndrome. However, more research is needed to understand the long-term clinical outcomes and establish the usefulness of this technique in guiding patient management. The article also includes tables summarizing previous studies on salivary gland ultrasonography findings in patients with Sjögren's syndrome. [Extracted from the article]

Introduction Submandibular gland fistula (SGF) is a rare subset of salivary gland fistulas. It is seldom tough to diagnose them prior to surgical exploration, and it is often clinically confused with close differentials. An early diagnosis based on pertinent clinical features and focused radiological findings can be pivotal in optimal management and help prevent recurrence and avoid unnecessary investigations/interventions. Objective To review articles that discuss SGF and provide vital etiological, clinical, and imaging features of this rare entity that can aid in early clinical diagnosis. Data Synthesis An extensive review involving PubMed and Google Scholar and reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) standards. Conclusion Submandibular gland fistula is a rare entity. It can be confused with close differentials, including branchial fistulas, if not thoroughly examined. Discharge from fistulae along with submandibular pain/tenderness and/or swelling are important diagnostic clues. A history of trauma, nodule at the site of discharge, prior submandibular disease/calculi, or discharge aggravated with food further increases a clinical suspicion. Optimal radiological investigation looking for calculi/foreign body and delineating the fistula tract is vital to affirm a diagnosis. Gland with fistula excision is a commonly advocated treatment of choice with no reports of recurrence, although conservative management and gland preserving surgery have also reported a favorable prognosis. [ABSTRACT FROM AUTHOR]

Objectives: Confirm that stem cells from human exfoliated deciduous teeth‐derived exosomes (SHED‐exos) can limit inflammation‐triggered epithelial cell apoptosis and explore the molecular mechanism. Methods: SHED‐exos were injected into the submandibular glands (SMGs) of non‐obese diabetic (NOD) mice, an animal model of Sjögren's syndrome (SS). Cell death was evaluated by western blotting and terminal deoxynucleotidyl transferase‐mediated dUTP nick‐end labelling staining. Results: SHED‐exos treatment promoted the saliva flow rates of NOD mice, accompanied by decreased cleaved caspase‐3 levels and apoptotic cell numbers in SMGs. SHED‐exos inhibited autophagy, pyroptosis, NETosis, ferroptosis, necroptosis and oxeiptosis marker expression in SS‐damaged glands. Mechanistically, Kyoto Encyclopedia of Genes and Genomes analysis of exosomal miRNAs suggested that the rat sarcoma virus (RAS)/mitogen‐activated protein kinase kinase (MEK)/extracellular signal‐regulated kinase (ERK) pathway might play an important role. In vivo, the expression of Kirsten RAS, Harvey RAS, MEK1/2 and p‐ERK1/2 was upregulated in SMGs, and this change was blocked by SHED‐exos treatment. In vitro, SHED‐exos suppressed p‐ERK1/2 activation and increased cleaved caspase‐3 and apoptotic cell numbers, which were induced by IFN‐γ. Conclusion: SHED‐exos suppress epithelial cell death, which is responsible for promoting salivary secretion. SHED‐exos inhibited inflammation‐triggered epithelial cell apoptosis by suppressing p‐ERK1/2 activation, which is involved in these effects. [ABSTRACT FROM AUTHOR]

Introduction: We investigated complications and recurrence rates after surgical techniques for sialolith removal with intact and resected Wharton's duct of the submandibular gland. Methods: The retrospective case–control analysis of a series analysed 271 surgical operations (2003–2022) for sialolithiasis performed at a hospital department of Otolaryngology—Head and Neck Surgery. The study compared two approaches: (1) pure endoscopic technique or pinpoint stone removal with Wharton's duct left intact and (2) transoral duct dissection or pinpoint stone removal technique, after which the duct was shortened. While choosing the surgical option, the size of the stone, the location of the stone, and the presence of multiple stones were taken into account. The rates of complications (lingual nerve paraesthesia, duct stenosis, drooling, and sialoadenitis), the incidence of foreign bodies, and the rate of recurrence during follow‐up of ≥18 months were compared. Results: 323 sialoliths were removed from 271 patients. Of these 323 calculi, 150 were removed by the first approach and 173 by the second approach. The calculi varied in diameter from 2 to 38 mm with an average diameter of 8.2 mm. For all 271 patients, the rate of recurrence was 4.8%, but 11 recurrent cases (8.7%) appeared after the first approach surgeries and 2 cases (1.4%) after the second approach surgeries (p =.03). Other variables did not show statistically significant differences. Conclusions: Surgical removal of the submandibular calculi, ending with shortening of Wharton's duct, reduces the recurrence rate for sialolithiasis but does not affect the rate of postsurgical complications. [ABSTRACT FROM AUTHOR]

Background: Microvascular complications of diabetes mellitus (DM) include oral manifestations and complications, including xerostomia, reduced salivary flow, susceptibility to infection, periodontal disease and salivary gland enlargement. Objective: The present study aims to evaluate B‐mode ultrasonography (USG) parameters such as size, volume and echogenicity of the submandibular and parotid salivary glands on both sides, shear‐wave elastography (SWE) value and colour Doppler properties in patients with DM and healthy control groups. Methods: In total, 160 right and left submandibular glands and 160 right and left parotid glands of 80 patients, 40 patients (20 type 1 DM, 20 type 2 DM) and 40 healthy control group, between the ages of 18–70 were examined by USG. Echogenicity, parenchyma internal structure, margin and dimensional measurements (antero‐posterior length, supero‐inferior length, medio‐lateral length and volume) and colour Doppler with 'ML 6‐15‐D Matrix Array (4‐15 MHz)' probe, shear‐wave elastography '9L‐D (2–8 MHz)' probe was investigated. Result: Statistically significant difference was observed in echogenicity in the right submandibular gland, echogenicity in the right parotid gland, margin characteristics, parenchymal homogeneity and colour Doppler characteristics between the type 1 DM, type 2 DM and control groups (p <.05). It was observed that the size, volume and SWE values of both submandibular and parotid glands were higher in the DM patient group than in the control group. Higher values were observed in type 2 DM compared to type 1 DM in the patient group. Conclusion: USG is an effective imaging technique in investigating the effects of diabetes on the submandibular and parotid salivary glands. [ABSTRACT FROM AUTHOR]

The diagnosis and treatment of Sjogren's syndrome (SS) are commonly conducted by rheumatologists and stomatologists. The purpose of this study was to compare the scientometric characteristics of SS publications by rheumatologists and stomatologists. All the papers on cheilitis were comprehensively retrieved from the Scopus database, and divided into rheumatologists and stomatologists groups. There were 3245 and 1209 papers on SS were published by rheumatologists and stomatologists, respectively. For the most-cited top-200 papers, the total citation count was 29,764 and the h index was 108 for SS publications by rheumatologists; whereas the count is 19,891 and h index is 81 for publications by stomatologists. Interestingly, we observed that accumulated citations of the publications by stomatologists cooperated with rheumatologists were larger than those by stomatologists alone during 2012–2022. The more common keywords such as saliva, salivation, minor salivary glands, parotid gland, submandibular gland, sialography, lip, dental caries, and hyposalivation were reported by stomatologists. The more frequent keywords such as rheumatoid factor, fatigue, lymphoma, interstitial lung disease, arthralgia, Raynaud phenomenon, lymphadenopathy, and vasculitis were reported by rheumatologists. This study firstly reports the scientometric characteristics of SS publications by rheumatologists and stomatologists. The scale and citations of rheumatologists' publications greatly outweigh those of stomatologists, suggesting stomatologists can cooperate more with rheumatologists regarding SS research. [ABSTRACT FROM AUTHOR]

Objectives: To investigate the utility of deep learning (DL)-based image reconstruction using a model-based approach in head and neck diffusion-weighted imaging (DWI). Materials and methods: We retrospectively analyzed the cases of 41 patients who underwent head/neck DWI. The DWI in 25 patients demonstrated an untreated lesion. We performed qualitative and quantitative assessments in the DWI analyses with both deep learning (DL)- and conventional parallel imaging (PI)-based reconstructions. For the qualitative assessment, we visually evaluated the overall image quality, soft tissue conspicuity, degree of artifact(s), and lesion conspicuity based on a five-point system. In the quantitative assessment, we measured the signal-to-noise ratio (SNR) of the bilateral parotid glands, submandibular gland, the posterior muscle, and the lesion. We then calculated the contrast-to-noise ratio (CNR) between the lesion and the adjacent muscle. Results: Significant differences were observed in the qualitative analysis between the DWI with PI-based and DL-based reconstructions for all of the evaluation items (p < 0.001). In the quantitative analysis, significant differences in the SNR and CNR between the DWI with PI-based and DL-based reconstructions were observed for all of the evaluation items (p = 0.002 ~ p < 0.001). Discussion: DL-based image reconstruction with the model-based technique effectively provided sufficient image quality in head/neck DWI. [ABSTRACT FROM AUTHOR]

Although mesenchyme is essential for inducing the epithelium of ectodermal organs, its precise role in organ-specific epithelial fate determination remains poorly understood. To elucidate the roles of tissue interactions in cellular differentiation, we performed single-cell RNA sequencing and imaging analyses on recombined tissues, where mesenchyme and epithelium were switched ex vivo between two types of embryonic mouse salivary glands: the parotid gland (a serous gland) and the submandibular gland (a predominantly mucous gland). We found partial induction of molecules that define gland-specific acinar and myoepithelial cells in recombined salivary epithelium. The parotid epithelium recombined with submandibular mesenchyme began to express mucous acinar genes not intrinsic to the parotid gland. While myoepithelial cells do not normally line parotid acini, newly induced myoepithelial cells densely populated recombined parotid acini. However, mucous acinar and myoepithelial markers continued to be expressed in submandibular epithelial cells recombined with parotid mesenchyme. Consequently, some epithelial cells appeared to be plastic, such that their fate could still be modified in response to mesenchymal signaling, whereas other epithelial cells appeared to be already committed to a specific fate. We also discovered evidence for bidirectional induction: transcriptional changes were observed not only in the epithelium but also in the mesenchyme after heterotypic tissue recombination. For example, parotid epithelium induced the expression of muscle-related genes in submandibular fibroblasts that began to mimic parotid fibroblast gene expression. These studies provide the first comprehensive unbiased molecular characterization of tissue recombination approaches exploring the regulation of cell fate. [ABSTRACT FROM AUTHOR]

Background: Angiosarcoma is a sarcoma that occurs in a range of tissue types, and only rarely in the salivary glands, showing a predilection for the parotid glands of older patients. Preoperative diagnosis may be challenging, especially on cytology, with significant morphological overlap with high-grade primary salivary gland carcinomas. The molecular alterations of this rare salivary gland neoplasm are also not well-characterized. Methods and Results: We present a case of right submandibular gland swelling in a 73-year-old male. On fine needle aspiration, including immunohistochemical stains on cell block, the tumor was initially diagnosed as poorly differentiated carcinoma. Resection of the submandibular gland revealed epithelioid angiosarcoma. We performed molecular work-up of the tumor, utilizing targeted next-generation sequencing, DNA methylation profiling and fluorescence in-situ hybridization. Histopathologic assessment revealed an infiltrative tumor comprising solid sheets of epithelioid cells. The tumor cells formed haphazardly anastomosing vascular channels with intracytoplasmic lumina containing red blood cells. On immunohistochemistry, the tumor cells were positive for CD31, CD34 and ERG. Approximately 40% of the tumor cells showed nuclear expression of GATA3. A pathogenic TP53 R267W mutation was detected on next-generation sequencing. DNA methylation analysis did not cluster the tumor with any known sarcoma type. Copy number analysis showed possible MYC amplification and CDKN2A losses, although only the latter was confirmed on fluorescence in-situ hybridization. Conclusion: Epithelioid angiosarcoma is an important differential diagnosis to high-grade salivary gland carcinoma. In particular, GATA3 expression may be encountered in both angiosarcoma and high-grade salivary gland carcinomas and cause diagnostic confusion. Identification of TP53 mutations and CDKN2A losses suggest shared oncogenic pathways with soft tissue angiosarcomas, and should be further investigated. [ABSTRACT FROM AUTHOR]

Introduction: Mobile phones are very useful but have negative impacts that emit radiation to their users and affect our health. Mobile phone electromagnetic waves can increase levels of Reactive Oxygen Species (ROS) leading to oxidative stress and causing damage to cells and tissues thereby reducing their function. Therefore this research investigates the effect of mobile phone radiation exposure on the malondialdehyde levels and alteration in salivary gland in rats. Materials and methods: Twelve Male Wistar Rats were randomly divided into 2 groups: the healthy group (HG), and the Radiation group (RG). The healthy group was healthy rats without cellphone radiation while the radiation group was given phone radiation exposure one hour per day for 21 days. Evaluation of oxidant level in the blood and submandibular gland by measuring malondialdehyde, and the salivary gland alteration by measuring degeneration of acinar cells in parotid glands. Data were analyzed using an Independent T-Test. Results: There were significant differences between groups for malondialdehyde (MDA) levels in the blood and submandibular glands shown by the Independent T-test. There was acinar cell degeneration in the parotid glands compared to the healthy group. Conclusion: One-hour phone radiation exposure increased MDA levels in blood and salivary glands, as well as induces cell damage. [ABSTRACT FROM AUTHOR]

Salivary gland tumors are relatively rare and can exhibit various clinical behaviors. The study aims to understand the natural history, pathology, diagnostic workup, and treatment strategies for these tumors to improve patient outcomes. The audit included patients with salivary gland tumors detected through radiology or cytology. Patients underwent surgery, with some receiving adjuvant treatment. Demographic information, treatment interventions, and survival outcomes were analyzed using SPSS software. A total 89 as malignant salivart gland tumours were audited Malignant tumors were predominantly found in the parotid gland, with fewer cases in the minor salivary gland and submandibular gland.The median age of presentation was 47 years, and the majority of patients were male. The study examined various pathological and clinical factors, including tumor stage, nodal status, and the presence of facial palsy. Surgical procedures and histological types of tumors were documented. Adverse histological features like positive margins, lymph node positivity, lympho-vascular invasion, extracapsular spread, and perineural invasion were noted. POSTOP RT was administered to high-risk patients. Most malignant salivary gland tumors were found in the parotid gland, while minor salivary gland tumors were underrepresented in the audit. Surgical practices were diverse. Radiotherapy protocols were relatively standardized. The study found that certain histological features, such as lymph node positivity, margin positivity, lympho-vascular invasion, perineural invasion, and extracapsular spread, were associated with adverse effects on DFS and OS. The findings suggest that specific histological features, including LVI and ECE have emerged as independent prognostic factors for DFS and OS. [ABSTRACT FROM AUTHOR]

Alpha-synuclein seed amplification assays (αSyn-SAAs) have emerged as promising diagnostic tools for Parkinson's disease (PD) by detecting misfolded αSyn and amplifying the signal through cyclic shaking and resting in vitro. Recently, our group and others have shown that multiple biospecimens, including CSF, skin, and submandibular glands (SMGs), can be used to seed the aggregation reaction and robustly distinguish between patients with PD and non-disease controls. The ultrasensitivity of the assay affords the ability to detect minute quantities of αSyn in peripheral tissues, but it also produces various technical challenges of variability. To address the problem of variability, we present a high-yield αSyn protein purification protocol for the efficient production of monomers with a low propensity for self-aggregation. We expressed wild-type αSyn in BL21 Escherichia coli, lysed the cells using osmotic shock, and isolated αSyn using acid precipitation and fast protein liquid chromatography (FPLC). Following purification, we optimized the ionic strength of the reaction buffer to distinguish the fluorescence maximum (Fmax) separation between disease and healthy control tissues for enhanced assay performance. Our protein purification protocol yielded high quantities of αSyn (average: 68.7 mg/mL per 1 L of culture) and showed highly precise and robust αSyn-SAA results using brain, skin, and SMGs with inter-lab validation. [ABSTRACT FROM AUTHOR]

Sublingual gland herniation into the submandibular space through a mylohyoid muscle defect is a common anatomical variation; however, salivary gland cancers that arise from a herniated sublingual gland have not been described yet. Here, we report three patients with salivary gland cancers originating from a herniated sublingual gland. All tumors were detected as palpable submandibular masses, located anterior to the submandibular gland, medial to the mandible, and lateral to the mylohyoid muscle, with contact with the sublingual gland through a mylohyoid muscle defect. Intraoperative findings confirmed that the masses were derived from herniated sublingual glands. Pathological examination showed one case of mucoepidermoid carcinoma and two cases of adenoid cystic carcinoma. Imaging findings of the tumor location, in addition to the continuity with the sublingual gland through the mylohyoid muscle defect, are crucial for accurately diagnosing the tumor origin, which is essential for determining the appropriate clinical management. [ABSTRACT FROM AUTHOR]

Background: Radiotherapy affects salivary glands more intensely than it does other organs, and salivary gland dysfunction can continue during or after treatment. The aim of this study was to examine structural alterations in submandibular glands through ultrasonography following head-neck radiotherapy in patients and to evaluate the impact of radiation dose on these modifications. Methods: Forty-six submandibular glands were assessed ultrasonographically for the changes in echogenicity, echotexture, and margin and the influence of the radiation dose on these changes before radiotherapy at 3 time points: the second and sixth months following starting treatment. Statistical analysis of the data was performed using a chi-square test. Results: Significant relationship in 3 ultrasonographic structural chara cteri stics --echo genic ity, echotexture, and margin-- of submandibular glands (P < .001, P < .001, and P < .001, respectively) were observed before and at the second and sixth months after radiotherapy. There was found a significant correlation between the radiation dose groups in the change of echotexture at 2 different time periods after radiotherapy (P < .001, P < .05, respectively) and in the change of margin at the second month after radiotherapy onset (P < .05). Conclusion: Preceding radiotherapy, submandibular glands typically exhibited hyperechoic echogenicity, homogeneous ecotextures, and regular margins. However, after radiotherapy, there was an observable transformation characterized by isoechoic/hypoechoic features, heterogeneous textures, and irregular margins. With the passage of time following radiotherapy, there was a tendency for the parenchyma structure to gradually revert to a normal state. Also, the radiation dose generally has an effect on the structural changes of the submandibular glands. [ABSTRACT FROM AUTHOR]

Background: Salivary gland tumors consist of a group of heterogeneous lesion with complex clinicopathological characteristics. Fine needle aspiration (FNA) cytology has been used as a quick, non-invasive diagnostic tool for the diagnosis of neoplastic and non-neoplastic lesion of salivary gland. Aims and Objectives: The aims and objectives of the study are to perform the cytopathological evaluation of minor and major salivary gland lesions (neoplastic and non-neoplastic) in terms of its various types, frequency, site, demographic distribution and to correlate with histopathology findings whenever available. Materials and Methods: This is a hospital-based 3-year study in which 155 cases of patient underwent FNA cytology for salivary gland swelling (non-neoplastic and neoplastic) of which seven cases were excluded due to scant and inadequate aspirate, and thus, only 148 cases were included in this study and histopathological correlation was available in 42 cases. Any metastatic lesion, repeat samples from same patient were excluded from the study. Results: Out of 148 cases, male patients were 72 (49%) and female patients were 76 (51%) with M: F ratio of 0.9:1. Benign lesion was commonly seen in 31-40 years, non-neoplastic lesion at 41-60 years (n=18, 37.6%), and malignant lesions at 61-90 years (n=9, 37.5%). Parotid was the most common salivary gland involved by neoplastic and non-neoplastic lesion accounting 65.5% (n=97) followed by submandibular gland 29.7% (n=34). Pleomorphic adenoma was most frequently diagnosed among all salivary gland lesions (60%). Mucoepidermoid carcinoma outnumbered the category (14%) of malignant salivary gland lesion. On histopathology correlation, 33 cases were correctly diagnosed in cytopathology whereas 9 cases showed discordant result. FNA cytology sensitivity was 66.6%, specificity was 93.3%, positive predictive value was 80.0%, and negative predictive value was 87.5%, respectively. Diagnostic accuracy was found to be 85.7%. Conclusion: Cytopathology examination of salivary gland can be used as safe and reliable method in primary diagnosis of lesions of salivary gland. [ABSTRACT FROM AUTHOR]

Background Injecting botulinum toxin (BTX) into the submandibular glands (SMGs) can treat drooling symptoms in neurological diseases and improve the aesthetics of SMG hypertrophy and ptotic SMGs. Objectives This study aimed to define the size and position of the SMGs by high-frequency ultrasound, and to perform statistical analysis to improve the safety and accuracy of BTX injection therapy. Methods Neck ultrasonography with high-frequency ultrasound was performed on 214 volunteers. The length, height, and thickness of the SMGs, and the distance between the SMGs and the midline, the anterior border of the sternocleidomastoid, the mandible, and the surface were measured. Results The SMGs were almond-shaped with a mean [standard deviation] length of 33.7 [4.7] mm, a thickness of 13.3 [2.9] mm, and a height of 27.6 [6.0] mm. The length and height were significantly different between underage and youth groups. The size of the SMGs did not show any notable differences with increasing BMI; however, their depth, and the distance from the mandible, midline, and anterior border of the sternocleidomastoid increased. No significant differences were observed between the affected and healthy sides in patients with microtia, hemifacial microsomia, or cleft lip and palate. Conclusions Ultrasound provides more comprehensive information regarding the size and position of the SMGs, which can serve as a reference in BTX therapy and in the diagnosis of SMG diseases involving size alterations. Level of Evidence: 4 [ABSTRACT FROM AUTHOR]

The major salivary glands are the paired parotid, submandibular, and sublingual glands. Salivary gland disorders can affect the glandular tissue or its excretory system. The parotid glands are the largest and produce aqueous serous secretions that are less immunogenic. They are more susceptible to infections and neoplasms. The submandibular glands produce mucinous secretions that are high in calcium and phosphate salts through a long submandibular duct that flows against gravity. The submandibular glands are responsible for more than 80% of salivary stones. Sialadenitis can be acute or chronic and caused by bacterial, viral, and obstructive etiologies; the most common bacteria is Staphylococcus aureus. The most common viral etiologies in children are mumps (globally) and juvenile recurrent parotitis (in vaccinated populations). Sialadenosis is a chronic asymptomatic enlargement of the salivary glands due to systemic disease. Sialolithiasis causes up to 50% of salivary gland disorders. It is associated with salivary stasis and inflammation caused by dehydration, malnutrition, medications, or chronic illness. Obstruction is also caused by trauma, stenosis, and mucoceles. Neoplasms are rare and typically benign, but they warrant referral and imaging with ultrasonography, computed tomography, or magnetic resonance sialography. Most disorders are managed with conservative measures by treating the underlying etiology, optimizing predisposing factors, controlling pain, and increasing salivary flow with sialagogues, hydration, massage, warm compresses, oral hygiene, and medication adjustment. Sialendoscopy is a gland-sparing technique that can treat obstructive and nonobstructive disorders. (Am Fam Physician. 2024; 109(6): 550–559. Copyright © 2024 American Academy of Family Physicians.) The major salivary glands are the paired parotid, submandibular, and sublingual glands. Salivary gland disorders can affect the glandular tissue or its excretory system. The parotid glands are the largest and produce aqueous serous secretions that are less immunogenic. They are more susceptible to infections and neoplasms. The submandibular glands produce mucinous secretions that are high in calcium and phosphate salts through a long submandibular duct that flows against gravity. The submandibular glands are responsible for more than 80% of salivary stones. Sialadenitis can be acute or chronic and caused by bacterial, viral, and obstructive etiologies; the most common bacteria is Staphylococcus aureus. The most common viral etiologies in children are mumps (globally) and juvenile recurrent parotitis (in vaccinated populations). Sialadenosis is a chronic asymptomatic enlargement of the salivary glands due to systemic disease. Sialolithiasis causes up to 50% of salivary gland disorders. It is associated with salivary stasis and inflammation caused by dehydration, malnutrition, medications, or chronic illness. Obstruction is also caused by trauma, stenosis, and mucoceles. Neoplasms are rare and typically benign, but they warrant referral and imaging with ultrasonography, computed tomography, or magnetic resonance sialography. Most disorders are managed with conservative measures by treating the underlying etiology, optimizing predisposing factors, controlling pain, and increasing salivary flow with sialagogues, hydration, massage, warm compresses, oral hygiene, and medication adjustment. Sialendoscopy is a gland-sparing technique that can treat obstructive and nonobstructive disorders. (Am Fam Physician. 2024;109(6):550-559. Copyright © 2024 American Academy of Family Physicians.) [ABSTRACT FROM AUTHOR]

Hyperphosphorylation of the microtubule-associated protein tau is hypothesized to lead to the development of neurofibrillary tangles in select brain regions during normal aging and in Alzheimer disease (AD). The distribution of neurofibrillary tangles is staged by its involvement starting in the transentorhinal regions of the brain and in final stages progress to neocortices. However, it has also been determined neurofibrillary tangles can extend into the spinal cord and select tau species are found in peripheral tissues and this may be depended on AD disease stage. To further understand the relationships of peripheral tissues to AD, we utilized biochemical methods to evaluate protein levels of total tau and phosphorylated tau (p-tau) as well as other neuronal proteins (i.e., tyrosine hydroxylase (TH), neurofilament heavy chain (NF-H), and microtubule-associated protein 2 (MAP2)) in the submandibular gland and frontal cortex of human cases across different clinicopathological stages of AD (n = 3 criteria not met or low, n = 6 intermediate, and n = 9 high likelihood that dementia is due to AD based on National Institute on Aging-Reagan criteria). We report differential protein levels based on the stage of AD, anatomic specific tau species, as well as differences in TH and NF-H. In addition, exploratory findings were made of the high molecular weight tau species big tau that is unique to peripheral tissues. Although sample sizes were small, these findings are, to our knowledge, the first comparison of these specific protein changes in these tissues.

Background: Primary Sjogren's syndrome (pSS) is a common chronic autoimmune disease that presents limited treatment options and poses significant challenges for patients. Maidong Dishao Decoction (MDDST), a traditional Chinese medicine compound, has demonstrated potential in alleviating dryness symptoms associated with pSS. Therefore, it is important to study the specific mechanism of its therapeutic effect. Objective: This study aims to investigate the effects of MDDST on gut microbiota, short-chain fatty acids (SCFAs), and the Th17/Treg immune balance in non-obese diabetes (NOD) mice. Methods: The study employed ultrahigh-performance liquid chromatography coupled with quadrupole-exactive mass spectrometry (UHPLC-QE-MS) to identify the primary components of MDDST. Subsequently, hematoxylin and eosin (HE) staining, enzyme-linked immunosorbent assays (ELISA), and flow cytometry analyses were conducted to evaluate the therapeutic effects of MDDST in NOD mice. Additionally, 16S rDNA sequencing and gas chromatography-mass spectrometry (GC-MS) were utilized to assess the influence of MDDST on gut microbiota and SCFAs. Finally, fecal microbiota transplantation (FMT) and SCFA-based interventions were performed to elucidate the mechanisms through which MDDST exerts its effects. Results: The research findings demonstrate that MDDST exerts therapeutic effects on NOD mice, primarily manifested as reduced inflammation, decreased water intake, ameliorated pathological changes and lowered levels of Sjogren's syndrome antigen A (SSA) and immunoglobulin G (IgG). Additionally, MDDST significantly decreased serum levels of interleukin-6 (IL-6) and interleukin-17 (IL-17), while enhancing levels of interleukin-10 (IL-10) and transforming growth factor beta (TGF-β), thereby regulating the Th17/Treg immune balance. Further investigations revealed that MDDST treatment induces alterations in gut microbiota composition and elevates SCFA levels in the gut. Subsequent FMT and SCFA intervention experiments demonstrated a downregulation of pSS-related phenotypes. Conclusion: In summary, MDDST demonstrates protective effects against pSS by restoring the balance between Th17 and Treg cells. The therapeutic effects can be partially attributed to its regulation of gut microbiota and SCFAs. Our finding provides a new option for treating pSS.

BackgroundSecretion of saliva is controlled by autonomic nerve signals via regulation of Ca2+-dependent ion transport across acinar cell membranes. Oxidative stress may affect this process, leading to a decrease in saliva production. This study investigates elements of the Ca2+ regulatory pathway and their vulnerability to hydrogen peroxide-induced oxidative stress.MethodsRat parotid and submandibular salivary gland acinar cell lines were exposed to different hydrogen peroxide concentrations to simulate oxidative stress. Cell viability and intracellular reactive oxygen species were measured, mRNA levels were assessed via RT-qPCR, and protein expression was studied using western blot and immunofluorescence microscopy.ResultsElevated concentrations of hydrogen peroxide reduced cell viability and increased intracellular levels of reactive oxygen species and led to a decrease in cholinergic receptor muscarinic 3 and adrenoreceptor alpha 1A mRNA and protein levels in both cell lines. In parotid gland cells, both mRNA and protein levels of stromal interaction molecule 1 and Orai1 decreased with increasing concentrations of hydrogen peroxide. In contrast, in submandibular gland cells stromal interaction molecule 1 and Orai1 displayed differential mRNA and protein expression levels.ConclusionOur study revealed that hydrogen peroxide exposure alters rat parotid and submandibular acinar cells, increasing reactive oxygen species and reducing autonomic receptor expression. Differential mRNA and protein expression of stromal interaction molecule 1 and Orai1 highlight complex oxidative stress effects on Ca2⁺ signaling. Most likely these effects will be deleterious to salivary secretion, but some effects may be protective.

Adenoid Cystic Carcinoma (ACC) is an uncommon form of malignant neoplasm of the salivary gland. ACC is a rare epithelial, slowgrowing yet aggressive neoplasm with a remarkable capacity for recurrence. It most commonly develops in the salivary glands or other regions of the head and neck. Hereby, authors present a case of a 72-year-old female who presented with a rapidly enlarging swelling in the right submandibular region, which had recurred three times. Histopathological examination reported it as ACC grade II. ACC is known for its ability to invade perineurally, its high frequency of local and distant recurrence and its poor long-term prognosis. In the present case, the treatment provided was complete surgical resection. The patient underwent wide surgical excision of the lesion with appropriate margins, as well as a completion neck dissection of level IA. The histopathological diagnosis is based on tissue examination findings that exhibit typical histologic features. The presence and percentage of solid architecture reflect clinical outcomes and should be reported in the pathology report. Current diagnostics mainly rely on histomorphology, along with immunohistochemistry and cytogenetics. Poor prognostic factors include large tumour size, solid growth pattern, positive surgical margins, nodal status, nuclear atypia, high mitotic activity, high-grade transformation, lymphovascular invasion and tumour necrosis. The patient was kept on regular follow-up and there was no recurrence or metastasis noted over two years. ACC remains extremely difficult to treat due to its high recurrence and metastasis rates. The authors are presenting a case of right submandibular gland ACC for its rarity, multiple recurrences, aggressive clinical behaviour and associated radiological and histopathological findings. [ABSTRACT FROM AUTHOR]

The article describes the case of a 23-year-old male without previous history of submandibular trauma and surgery, infection, and viral illness with left submandibular painless swelling. Topics discussed include finding on magnetic resonance imaging (MRI), his diagnosis of sublingual gland (SLG) mucocele, and treatments of SMG mucocele.

Background The association of chronic sclerosing sialadenitis and IgG4-related disease (IgG4-RD) has resulted in the more frequent identification of IgG4-positivity in submandibular gland inflammations, also uncovering IgG4 overexpression in nonspecific inflammations. These findings lead us to hypothesise that IgG4-positive sialadenitis represents a continuous inflammatory process overlapping histologically with IgG4-RD, possibly differing in aetiology. However, the antigen underlying IgG4 overexpression in IgG4-positive sialadenitis and IgG4-RD remains unknown.Materials and methods Here, we investigated toll-like receptor (TLR) – mediated bacterial inflammation in submandibular gland tissues of patients with IgG4-positive and IgG4-negative chronic inflammatory lesions of the submandibular gland (n = 61), with noninflamed submandibular glands serving as controls (n = 4). Utilising immunohistochemistry, we assessed the expression of TLR2 and TLR4, lipopolysaccharide (LPS) and the P. gingivalis-specific antigen gingipain R1.Results We observed TLR2- and TLR4-immunopositivity in 64 (98%) samples. However, TLR2 and TLR4 staining intensity was significantly stronger in the IgG4-positive group. LPS- and gingipain R1 immunopositivity were observed in 56 (86%) and 58 (89%) samples, respectively. LPS-positivity localised exclusively in mast cell-like cells, while gingipain R1-positivity remained scarce.Conclusions A stronger TLR2 or TLR4 expression in IgG4-positive sialadenitis may indicate a tissue-related factor underlying this form of chronic sialadenitis. LPS- and P. gingivalis immunopositivity remained weak throughout this series. Thus, gram-negative bacteria may not represent pathogens underlying these forms of chronic sialadenitis.

Background: This study aimed to assess the long-term effect of level IIb clinical target volume (CTV) optimisation on survival, xerostomia, and dysphagia in patients with nasopharyngeal carcinoma (NPC). Methods: Clinical data of 415 patients with NPC treated with intensity-modulated radiotherapy between December 2014 and October 2018 were retrospectively analysed. The patients were categorised into modified and comparison groups. Late xerostomia and dysphagia were evaluated using Radiation Therapy Oncology Group/European Organisation for Research and Treatment of Cancer scoring. Survival analysis was performed using the Kaplan–Meier method. Differences in late toxicity and dose parameters between both groups were compared. Prognostic factors for survival and late toxicity were assessed using regression analyses. Results: Patients in the modified group developed late xerostomia and dysphagia less frequently than those in the comparison group did (P < 0.001). The mean dose (Dmean) and V26 of parotid glands; Dmean and V39 of submandibular glands; and Dmean of sublingual glands, oral cavity, larynx, and superior, middle, and lower pharyngeal constrictor muscles were lower in the modified group than those in the comparison group (all P < 0.001). Both groups had no significant differences in overall, local recurrence-free, distant metastasis-free, or progression-free survival. The Dmean of the parotid and sublingual glands was a risk factor for xerostomia. The Dmean of the parotid and sublingual glands and middle pharyngeal constrictor muscle was a risk factor for dysphagia. Conclusions: Level IIb optimisation in NPC patients who meet certain criteria specially the exclusion of positive retropharyngeal nodes treated with intensity-modulated radiotherapy has the potential to better protect the salivary and swallowing structures, decreasing the development of late radiation-induced xerostomia and dysphagia while maintaining long-term survival. [ABSTRACT FROM AUTHOR]

Branching morphogenesis is a complex process shared by many organs including the lungs, kidney, prostate, as well as several exocrine organs including the salivary, mammary and lacrimal glands. This critical developmental program ensures the expansion of an organ's surface area thereby maximizing processes of cellular secretion or absorption. It is guided by reciprocal signaling from the epithelial and mesenchymal cells. While signaling pathways driving salivary gland branching morphogenesis have been relatively well-studied, our understanding of the underlying transcriptional regulatory mechanisms directing this program, is limited. Here, we performed in vivo and ex vivo studies of the embryonic mouse submandibular gland to determine the function of the transcription factor ΔNp63, in directing branching morphogenesis. Our studies show that loss of ΔNp63 results in alterations in the differentiation program of the ductal cells which is accompanied by a dramatic reduction in branching morphogenesis that is mediated by dysregulation of WNT signaling. We show that ΔNp63 modulates WNT signaling to promote branching morphogenesis by directly regulating Sfrp1 expression. Collectively, our findings have revealed a novel role for ΔNp63 in the regulation of this critical process and offers a better understanding of the transcriptional networks involved in branching morphogenesis. [ABSTRACT FROM AUTHOR]

Objectives: To identify the specific microRNAs (miRNAs) in IgG4-related dacryoadenitis and sialadenitis (IgG4-DS) and predict the targeted genes. Methods: miRNAs in the serum of nine patients with IgG4-DS, three patients with primary Sjögren's syndrome, and three healthy controls were analysed using the human miRNA chip, and miRNAs that exhibited significant fluctuation in expression in IgG4-DS patients were extracted. The respective target genes were predicted using an existing database, and expression of the target genes was evaluated in actual submandibular gland tissues affected by IgG4-DS. Results: Serum miR-125a-3p and miR-125b-1-3p levels were elevated in IgG4-DS. Six candidate target genes (glypican 4, forkhead box C1, protein tyrosine phosphatase non-receptor type 3, hydroxycarboxylic acid receptor 1, major facilitator superfamily domain containing 11, and tumour-associated calcium signal transducer 2) were downregulated in the affected submandibular gland tissue. Conclusion: Overexpression of miR-125a-3p and miR-125b-1-3p is a hallmark of IgG4-DS. These miRNAs appear to be involved in the pathogenesis of IgG4-DS. [ABSTRACT FROM AUTHOR]

Immunoglobulin G4 (IgG4)-related disease is an immune-mediated disorder that commonly manifests in the salivary glands. As a recently described disorder, the description and classification of IgG4-related disease is an ongoing process. Diagnosis of IgG4-related disease requires integration of clinical history, histopathology, and radiographic findings, including ultrasonography and sialography. In this case report, we correlate parotid ultrasonographic and sialographic findings in a patient with proven IgG4-related disorder confirmed from analysis of previous submandibular gland resections. We aim to highlight the utility of multimodality imaging in the diagnosis of IgG4-related disease. [ABSTRACT FROM AUTHOR]

Sjogren's syndrome (SS) is a complex systemic autoimmune disease. This study aims to elucidate a humanized NOD-PrkdcscidIl2rgem1/Smoc (NSG) murine model to better clarify the pathogenesis of SS. NSG female mice were adoptively transferred with 10 million peripheral blood mononuclear cells (PBMCs) through the tail vein from healthy controls (HCs), primary Sjogren's syndrome (pSS), and systemic lupus erythematosus (SLE) patients on D0. The mice were subcutaneously injected with C57/B6j submandibular gland (SG) protein or phosphate-buffered saline on D3, D17 and D31, respectively. NSG mice were successfully transplanted with human PBMCs. Compared with NSG-HC group, NSG-pSS and NSG-SLE mice exhibited a large number of lymphocytes infiltration in the SG, decreased salivary flow rate, lung involvement, decreased expression of genes related to salivary secretion, and the production of autoantibodies. Type I interferon-related genes were increased in the SG of NSG-pSS and NSG-SLE mice. The ratio of BAX/BCL2, BAX, cleaved caspase3, and TUNEL staining were increased in the SG of NSG-pSS and NSG-SLE mice. The expressions of p-MLKL and p-RIPK3 were increased in the SG of NSG-pSS and NSG-SLE mice. Increased expression of type I interferon-related genes, PANoptosis (apoptosis and necroptosis) were identified in the SG of this typical humanized NSG murine model of SS. [ABSTRACT FROM AUTHOR]

Objective: To perform a systematic review and meta‐analysis on the efficacy and safety of sialendoscopy in the treatment of obstructive diseases of the major salivary glands. Materials and Methods: We searched four databases for literature. The primary outcome assessed was the success rate. Secondary outcomes included the use of supportive devices, number of sialadenectomies and complications. Risk of bias was assessed. Meta‐analyses with subgroup analysis were performed. Results: In total, 91 studies were included, comprising 8218 patients undergoing 9043 sialendoscopic procedures. The majority of studies had a medium or high risk of bias. The incidence of sialadenectomy varied from 0% to 14%. No major complications were reported. Meta‐analysis revealed a weighted pooled success rate of 80.9%. Subgroup analyses showed the weighted pooled success rate in patients with sialoliths (89.6%), stenoses (56.3%), submandibular glands (88.3%), parotid glands (81.2%), patients treated by an endoscopic‐assisted transoral removal of a sialolith (86.3%), patients treated by a combined approach of the parotid gland (78.2%), patients with JRP (67.0%) and with RAIS (45.8%). Conclusion: The success rate of sialendoscopy did not considerably change in the last 9 years. Sialendoscopy is an efficient and safe procedure for the treatment of major salivary gland obstructive disease. [ABSTRACT FROM AUTHOR]

Aplasia of lacrimal and salivary glands (ALSG) is a syndromic disorder characterized by aplasia of lacrimal and salivary systems. Reported ophthalmic manifestations of ALSG include aplasia of lacrimal glands, punctal agenesis, lacrimal sac mucocele, and membranous congenital nasolacrimal duct obstruction (CNLDO). Bony CNLDO, a rare clinical entity, has not been associated with any syndromic disorder. This study investigated the relationship between genetic mutations and bony CNLDO in 3 Chinese families with ALSG. Single-center observational case study. Three Chinese families with bony CNLDO, including 7 affected and 9 healthy family members. Slit-lamp ophthalmic examination, comprehensive physical examination, orbital computed tomography (CT) imaging, cervicofacial magnetic resonance imaging, audiometry, and whole exome sequencing on periphery blood were performed. Variants were cross-referenced with 1000 control genomes and various population databases. Pathologic variants were identified using bioinformatic tools. Clinical examination, diagnostic imaging, whole exome sequencing, and bioinformatic analysis findings. Affected patients showed decreased tear production on the Schimer I test and reduced tear breakup time. Bony CNLDO was observed on CT, showing unilateral or bilateral bony termination at the middle or terminal segment of the nasolacrimal canal. Magnetic resonance imaging showed aplasia or absence of lacrimal, parotid, and submandibular glands. Physical examination revealed normal ears, digits, and facial morphology. Audiometry and dental assessment were conducted on the pediatric patients and yielded normal results. The clinical characteristics of patients aligned with a diagnosis of ALSG. Genomic analysis revealed 3 novel heterozygous missense mutations of the Fgf10 gene: c.316T→C, c.327C→G, and c.332T→G. The inheritance pattern was autosomal dominant with variable penetrance. These variants were not observed in 1000 control genomes and population databases. These variant positions also were shown to be highly conserved across various animal species. Mutated genes and proteins were predicted as deleterious with most computational models, with a few suggesting they may be benign. Bony CNLDO was identified as a novel phenotype of ALSG implicated by missense mutations of highly conserved residues in the Fgf10 gene. These cases broadened our knowledge of Fgf10 -related phenotypes and prompted clinicians to consider syndromic associations in patients with bony CNLDO. The author(s) have no proprietary or commercial interest in any materials discussed in this article. [ABSTRACT FROM AUTHOR]

BACKGROUND: The study aimed to investigate anatomical changes in the neck region and evaluate their impact on dose distribution in patients with nasopharyngeal carcinoma (NPC) undergoing intensity modulated radiation therapy (IMRT). Additionally, the study sought to determine the optimal time for replanning during the course of treatment. METHODS: Twenty patients diagnosed with NPC underwent IMRT, with weekly pretreatment kV fan beam computed tomography (FBCT) scans in the treatment room. Metastasized lymph nodes in the neck region and organs at risk (OARs) were redelineation using the images from the FBCT scans. Subsequently, the original treatment plan (PLAN0) was replicated to each FBCT scan to generate new plans labeled as PLAN 1–6. The dose-volume histograms (DVH) of the new plans and the original plan were compared. One-way repeated measure ANOVA was utilized to establish threshold(s) at various time points. The presence of such threshold(s) would signify significant change(s), suggesting the need for replanning. RESULTS: Progressive volume reductions were observed over time in the neck region, the gross target volume for metastatic lymph nodes (GTVnd), as well as the submandibular glands and parotids. Compared to PLAN0, the mean dose (Dmean) of GTVnd-L significantly increased in PLAN5, while the minimum dose covering 95% of the volume (D95%) of PGTVnd-L showed a significant decrease from PLAN3 to PLAN6. Similarly, the Dmean of GTVnd-R significantly increased from PLAN4 to PLAN6, whereas the D95% of PGTVnd-R exhibited a significant decrease during the same period. Furthermore, the dose of bilateral parotid glands, bilateral submandibular glands, brainstem and spinal cord was gradually increased in the middle and late period of treatment. CONCLUSION: Significant anatomical and dosimetric changes were noted in both the target volumes and OARs. Considering the thresholds identified, it is imperative to undertake replanning at approximately 20 fractions. This measure ensures the delivery of adequate doses to target volumes while mitigating the risk of overdosing on OARs. [ABSTRACT FROM AUTHOR]

Toxicities from head and neck (H&N) radiotherapy (RT) may affect patient quality of life and can be dose-limiting. Proteins from the transforming growth factor beta (TGF-β) family are key players in the fibrotic response. While TGF-β1 is known to be pro-fibrotic, TGF-β3 has mainly been considered anti-fibrotic. Moreover, TGF-β3 has been shown to act protective against acute toxicities after radio- and chemotherapy. In the present study, we investigated the effect of TGF-β3 treatment during fractionated H&N RT in a mouse model. 30 C57BL/6J mice were assigned to three treatment groups. The RT + TGF-β3 group received local fractionated H&N RT with 66 Gy over five days, combined with TGF-β3-injections at 24-hour intervals. Animals in the RT reference group received identical RT without TGF-β3 treatment. The non-irradiated control group was sham-irradiated according to the same RT schedule. In the follow-up period, body weight and symptoms of oral mucositis and lip dermatitis were monitored. Saliva was sampled at five time points. The experiment was terminated 105 d after the first RT fraction. Submandibular and sublingual glands were preserved, sectioned, and stained with Masson's trichrome to visualize collagen. A subset of mice in the RT + TGF-β3 group displayed increased severity of oral mucositis and increased weight loss, resulting in a significant increase in mortality. Collagen content was significantly increased in the submandibular and sublingual glands for the surviving RT + TGF-β3 mice, compared with non-irradiated controls. In the RT reference group, collagen content was significantly increased in the submandibular gland only. Both RT groups displayed lower saliva production after treatment compared to controls. TGF-β3 treatment did not impact saliva production. When repeatedly administered during fractionated RT at the current dose, TGF-β3 treatment increased acute H&N radiation toxicities and increased mortality. Furthermore, TGF-β3 treatment may increase the severity of radiation-induced salivary gland fibrosis. [ABSTRACT FROM AUTHOR]

The article explores a modified technique called submandibular degloving for submandibular sialoadenectomy, a surgical procedure to remove the submandibular gland. The technique aims to minimize complications by preserving the fascia, facial vessels, and nerves. The study presents the outcomes of 35 cases using this technique, demonstrating no recurrences of neoplastic lesions and a low rate of nerve injuries. While the technique shows promise, the study acknowledges limitations such as being a single-center case series and lacking a control group, highlighting the need for further research to validate the findings. [Extracted from the article]

Key Clinical Message: FBS is associated with surgical interventions or malignancies and could occur idiopathically. Also, this case highlights the successful management of FBS symptoms with pharmacological intervention with gabapentin and carbamazepine. [ABSTRACT FROM AUTHOR]