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ABSTRACT Background Methods Results Conclusions This meta‐analysis summarizes the current evidence on the intra‐ and inter‐observer agreement between WHO and the binary grading systems used to assess epithelial dysplasia (ED).A systematic search for observational studies that compared the level of agreement among pathologists between WHO and binary grading systems for ED was conducted using three databases: Medline, Scopus, and EBSCOhost. For the meta‐analysis, summary estimations of kappa value (κ) and standard error (SE) were utilized.The pooled analysis of observations by 46 pathologists from a total of eight studies showed better interobserver agreement in the interpretation of ED for the binary system (κ = 0.31; 95% confidence interval [CI], 0.23–0.40) in comparison with the WHO (κ = 0.14; 95% CI, 0.10–0.19). The intra‐observer agreement was reported only by five studies and was also found to be higher for the binary system (κ = 0.44; 95% CI, 0.31–0.57) compared to the WHO (κ = 0.25; 95% CI, 0.11–0.39).Our results validate that the binary system has better overall intra‐observer and interobserver agreement than the WHO system. Further studies with larger cohorts are mandatory before clinically relevant conclusions are drawn, as evidence remains inadequate. [ABSTRACT FROM AUTHOR]

The oral squamous cell carcinoma (OSCC) 5 year survival rate of 41% has marginally improved in the last few years, with less than a 1% improvement per year from 2005 to 2017, with higher survival rates when detected at early stages. Based on histopathological grading of oral dysplasia, it is estimated that severe dysplasia has a malignant transformation rate of 7%–50%. Despite these numbers, oral dysplasia grading does not reliably predict its clinical behavior. Thus, more accurate markers predicting oral dysplasia progression to cancer would enable better targeting of these lesions for closer follow‐up, especially in the early stages of the disease. In this context, molecular biomarkers derived from genetics, proteins, and metabolites play key roles in clinical oncology. These molecular signatures can help predict the likelihood of OSCC development and/or progression and have the potential to detect the disease at an early stage and, support treatment decision‐making and predict treatment responsiveness. Also, identifying reliable biomarkers for OSCC detection that can be obtained non‐invasively would enhance management of OSCC. This review will discuss biomarkers for OSCC that have emerged from different biological areas, including genomics, transcriptomics, proteomics, metabolomics, immunomics, and microbiomics. [ABSTRACT FROM AUTHOR]

Abstract Background Exercise is widely considered to have beneficial impact on skeletal muscle aging. In addition, there are also several studies demonstrating a positive effect of exercise on muscular dystrophies. Oculopharyngeal muscular dystrophy (OPMD) is a late‐onset autosomal dominant inherited neuromuscular disorder caused by mutations in the PAPBN1 gene. These mutations consist in short (1‐8) and meiotically stable GCN trinucleotide repeat expansions in its coding region responsible for the formation of PAPBN1 intranuclear aggregates. This study aims to characterize the effects of two types of chronic exercise, resistance and endurance, on the OPMD skeletal muscle phenotype using a relevant murine model of OPMD. Methods In this study, we tested two protocols of exercise. In the first, based on endurance exercise, FvB (wild‐type) and A17 (OPMD) mice underwent a 6‐week‐long motorized treadmill protocol consisting in three sessions per week of running 20 cm/s for 20 min. In the second protocol, based on resistance exercise generated by chronic mechanical overload (OVL), surgical removal of gastrocnemius and soleus muscles was performed, inducing hypertrophy of the plantaris muscle. In both types of exercise, muscles of A17 and FvB mice were compared with those of respective sedentary mice. For all the groups, force measurement, muscle histology, and molecular analyses were conducted. Results Following the endurance exercise protocol, we did not observe any major changes in the muscle physiological parameters, but an increase in the number of PABPN1 intranuclear aggregates in both tibialis anterior (+24%, **P = 0.0026) and gastrocnemius (+18%, ****P

Abstract Background Betel quid and its major ingredient, areca nut, are recognized by IARC as major risk factors in oral cancer development. Areca nut extract (ANE) exposure has been linked to OPMD progression and malignant transformation to OSCC. However, the detailed mechanism through which ANE acts on other cell types in the oral microenvironment to promote oral carcinogenesis remains elusive. Methods Immunoprofiling of macrophages associated with OPMD and OSCC was carried out by immunohistochemical and immunofluorescence staining. Phosphokinase and cytokine arrays and western blotting were performed to determine the underlying mechanisms. Transwell assays were used to evaluate the migration-promoting effect of ANE. Hamster model was finally applied to confirm the in vivo effect of ANE. Results We reported that M2 macrophages positively correlated with oral cancer progression. ANE induced M2 macrophage differentiation, CREB phosphorylation and VCAM-1 secretion and increased mitochondrial metabolism. Conditioned medium and VCAM-1 from ANE-treated macrophages promoted migration and mesenchymal phenotypes in oral precancer cells. In vivo studies showed that ANE enhanced M2 polarization and related signaling pathways in the oral buccal tissues of hamsters. Conclusion Our study provides novel mechanisms for areca nut-induced oral carcinogenesis, demonstrating that areca nut promotes M2 macrophage differentiation and secretion of oncogenic cytokines that critically activate malignant transformation of oral premalignant cells.

This manuscript critically examines the current classification of oral potentially malignant disorders, questioning the practicality and implications of labeling such a large population as precancerous, given that the actual progression to oral cancer is significantly low for most disorders. The paper advocates for a revised classification system that accurately reflects the varying malignancy risks associated with different disorders. It suggests a reassessment of the diagnostic and management approaches to mitigate overdiagnosis and alleviate patient burdens. We propose categorizing diseases with oral malignant potential as follows: Oral Precancerous Diseases, encompassing high‐risk lesions and conditions like erythroplakia, non‐homogeneous leukoplakia, proliferative leukoplakia, and actinic keratosis; Oral Potentially Premalignant Diseases, covering lesions, conditions, and systemic diseases with distinct oral manifestations harboring a limited or undefined risk of transformation, such as homogeneous leukoplakia, oral submucous fibrosis, oral lichenoid diseases, chronic hyperplastic candidosis, keratosis of known aetiology (smokeless tobacco, khat), palatal lesions in reverse smokers, and dyskeratosis congenita; and Systemic Conditions with Oral Malignant Potential including Fanconi's anemia, xeroderma pigmentosum, and chronic immunosuppression (including patients post‐bone marrow transplantation), which are associated with an increased risk of oral cancer without preceding precursor lesions. We provide illustrative examples to demonstrate how this framework offers practical guidance for research, policy‐making, and clinical practice. [ABSTRACT FROM AUTHOR]

Background: Betel quid and its major ingredient, areca nut, are recognized by IARC as major risk factors in oral cancer development. Areca nut extract (ANE) exposure has been linked to OPMD progression and malignant transformation to OSCC. However, the detailed mechanism through which ANE acts on other cell types in the oral microenvironment to promote oral carcinogenesis remains elusive. Methods: Immunoprofiling of macrophages associated with OPMD and OSCC was carried out by immunohistochemical and immunofluorescence staining. Phosphokinase and cytokine arrays and western blotting were performed to determine the underlying mechanisms. Transwell assays were used to evaluate the migration-promoting effect of ANE. Hamster model was finally applied to confirm the in vivo effect of ANE. Results: We reported that M2 macrophages positively correlated with oral cancer progression. ANE induced M2 macrophage differentiation, CREB phosphorylation and VCAM-1 secretion and increased mitochondrial metabolism. Conditioned medium and VCAM-1 from ANE-treated macrophages promoted migration and mesenchymal phenotypes in oral precancer cells. In vivo studies showed that ANE enhanced M2 polarization and related signaling pathways in the oral buccal tissues of hamsters. Conclusion: Our study provides novel mechanisms for areca nut-induced oral carcinogenesis, demonstrating that areca nut promotes M2 macrophage differentiation and secretion of oncogenic cytokines that critically activate malignant transformation of oral premalignant cells. [ABSTRACT FROM AUTHOR]

High levels of vascular endothelial growth factor (VEGF), fibroblast growth factor (FGF)-2 and angiopoietin (ANG)-2 are found in tissues from oral squamous cell carcinoma (OSCC) and oral potentially malignant disorders (OPMDs). As might be expected, VEGF, FGF-2, and ANG-2 overexpression parallels the development of new blood and lymphatic vessels that nourish the growing OPMDs or OSCCs and provide the latter with metastatic routes. Notably, VEGF, FGF-2, and ANG-2 are also linked to the epithelial-to-mesenchymal transition (EMT), a trans-differentiation process that respectively promotes or exasperates the invasiveness of normal and neoplastic oral epithelial cells. Here, we have summarized published work regarding the impact that the interplay among VEGF, FGF-2, ANG-2, vessel generation, and EMT has on oral carcinogenesis. Results from the reviewed studies indicate that VEGF, FGF-2, and ANG-2 spark either protein kinase B (AKT) or mitogen-activated protein kinases (MAPK), two signaling pathways that can promote both EMT and new vessels' formation in OPMDs and OSCCs. Since EMT and vessel generation are key to the onset and progression of OSCC, as well as to its radio- and chemo-resistance, these data encourage including AKT or MAPK inhibitors and/or antiangiogenic drugs in the treatment of this malignancy. [ABSTRACT FROM AUTHOR]

Oral potentially malignant disorders (OPMDs) are a group of conditions that carry a risk of oral squamous cell carcinoma (OSCC) development. Recent studies indicate that periodontal disease-associated pathogenic bacteria may play a role in the transition from healthy mucosa to dysplasia and to OSCC. Yet, the microbial signatures associated with the transition from healthy mucosa to dysplasia have not been established. To characterize oral microbial signatures at these different sites, we performed a 16S sequencing analysis of both oral swab and formalin-fixed, paraffin-embedded tissue (FFPE) samples. We collected oral swabs from healthy mucosa (from healthy patients), histologically normal mucosa adjacent to dysplasia, and low-grade oral dysplasia. Additionally, FFPE samples from histologically normal mucosa adjacent to OSCC, plus low grade and high-grade oral dysplasia samples were also collected. The collected data demonstrate significant differences in the alpha and beta microbial diversities of different sites in oral mucosa, dysplasia, and OSCC, as well as increased dissimilarities within these sites. We found that the Proteobacteria phyla abundance increased, concurrent with a progressive decrease in the Firmicutes phyla abundance, as well as altered levels of Enterococcus cecorum, Fusobacterium periodonticum, Prevotella melaninogenica, and Fusobacterium canifelinum when moving from healthy to diseased sites. Moreover, the swab sample analysis indicates that the oral microbiome may be altered in areas that are histologically normal, including in mucosa adjacent to dysplasia. Furthermore, trends in specific microbiome changes in oral swab samples preceded those in the tissues, signifying early detection opportunities for clinical diagnosis. In addition, we evaluated the gene expression profile of OSCC cells (HSC-3) infected with either P. gingivalis, T. denticola, F. nucelatum, or S. sanguinis and found that the three periodontopathogens enrich genetic processes related to cancer progression, including skin keratinization/cornification, while the commensal enriched processes related to RNA processing and adhesion. Finally, we reviewed the dysplasia microbiome literature and found a significant decrease in commensal bacteria, such as the Streptococci genus, and a simultaneous increase in pathogenic bacteria, mainly Bacteroidetes phyla and Fusobacterium genus. These findings suggest that features of the oral microbiome can serve as novel biomarkers for dysplasia and OSCC disease progression.

Background: pl6 (CDKN2a) play a role in tumorigenesis in some head and neck squamous cell carcinomas. Frequent homozygous deletions of the pl6 gene have been reported in many tumor cell lines including the brain, breast, osteosarcomas, melanomas, kidney, bladder, and ovary. Materials and methods: 5 patients without any tobacco using habit were included in group I as controls. 10 clinically and histopathologically confirmed cases of oral potentially malignant disorders (OPMDs) [oral submucous fibrosis (OSMF) −7 & leukoplakia (moderate dysplasia) −3] were included in group II. 10 clinically and histopathologically confirmed cases of OSCC were categorized as group III. Buccal scrapings were taken and analyzed for exon 1, 2, 3 of p16 and homozygous deletion in exon 2 of p16 was also detected by PCR and gel electrophoresis. Results: PCR amplification products of exon 1, 2, 3 of p16 were found in all 25 samples which include 10 cases of OSCC, 10 cases of OPMDs and 5 controls. Homozygous deletion in exon 2 was found only in 30 % of OSCC and 20 % of OPMD. Conclusion: Our study showed that cytological samples yield sufficient amount of DNA, which showed 100 % positivity with exon 1, 2, 3 of p16 gene, but the percentage of genetic alteration of p16 gene seems to be less when compared with other related studies.

Abstract Detection of subjects with oral potentially malignant disorders in a population is key to early detection of oral cancer (OC) with consequent reduction of cancer-related morbidity and mortality. Our aim was to investigate the prevalence and associated risk factors for OPMD in representative provinces of Indonesia. This cross-sectional study was undertaken in five Indonesian provinces: West Java (WJ), Jakarta (JKT), West Papua (WP), West Kalimantan (WK) and Banda Aceh (BA). Respondents answered a previously validated questionnaire including information on ethnicity, occupation, socioeconomic status (SES), oral health practices, and behaviours associated with oral cancer. An oral examination was undertaken using WHO standardized methodology. Data were analysed using ANOVA, Chi-Square, and logistic regression to assess association between risk factors and mucosal disease. A total of 973 respondents between the ages of 17 and 82 years was enrolled (WJ 35.5%,JKT 13.3% WP 18.3%, WK 9%, BA 23.9%). Tobacco smoking (14.8%), Betel quid (BQ) chewing (12.6%) and alcohol drinking (4%) varied geographically. A well-established OPMD was detected in 137 (14.1%) respondents and 2 (0.2%) presented with chronic ulceration later diagnosed as OC. Leukoplakia was the most common OPMD found (9.7%), while the prevalence of oral submucous fibrosis (OSMF), not previously described in the nation, was 2.3%. Poor knowledge of OC risk factors, poor oral hygiene behaviours, low-income SES and ethnicity were significantly associated with the presence of an OPMD. There is a previously under-reported high prevalence of OPMD in Indonesia. Overall, we found a strong correlation between the presence of an OPMD and individual habituation to known risk factors.

Oral Potentially Malignant Disorder (OPMD) is a significant concern for clinicians due to the risk of malignant transformation. Oral Squamous Cell Carcinoma (OSCC) is a common type of cancer with a low survival rate, causing over 200,000 new cases globally each year. Despite advancements in diagnosis and treatment, the five-year survival rate for OSCC patients remains under 50%. Early diagnosis can greatly improve the chances of survival. Therefore, understanding the development and transformation of OSCC and developing new diagnostic methods is crucial. The field of oral medicine has been advanced by technological and molecular innovations, leading to the integration of new medical technologies into dental practice. This study aims to outline the potential role of non-invasive imaging techniques and molecular signatures for the early detection of Oral Malignant and Potentially Malignant Disorders. [ABSTRACT FROM AUTHOR]

Introduction: The most effective means for reducing oral cancer (OC) mortality is by preventing late‐stage disease. Early diagnosis can be improved by increasing awareness among healthcare providers, specifically general dental practitioners (GDP). Therefore, our study aimed to assess GDPs' knowledge of OC risk factors and perceived competence in performing conventional oral examination (COE) in routine dental practice. Material and Methods: This was a cross‐sectional study conducted in five provinces of Indonesia, namely: Aceh, Banda Aceh (BA); Bandung, West Java (WJ); special district Jakarta (JKT), JKT; Pontianak, West Kalimantan (WK); and Sorong, West Papua (WP). The local Dental Association or Faculty of Dentistry invited the GDPs to attend an education program and complete the survey. Results: One hundred seventy‐seven GDPs completed the survey (WJ, n = 63; BA, n = 44, JKT, n = 27; WP, n = 23; and WP, n = 20). A large proportion (164 out of 177, 92.66%) of GDPs felt they had received insufficient training to equip them to diagnose OC and as many as 22.6% (n = 40) did not refer to specialists when they found suspicious mucosal lesions. Notwithstanding the significant regional variations, the majority of Indonesian GDPs self‐reported inadequate knowledge and awareness of OC and scarce confidence in performing COE. Conclusion: GDP knowledge of OC risk factors and COE is key to improving early diagnosis of OC at a community level. Therefore, it is suggested that the lack of knowledge and confidence of GDPs reported here should be addressed through the national dental curriculum in Indonesia. [ABSTRACT FROM AUTHOR]

Objectives: The aim of this systematic review and meta-analysis is to assess the diagnostic potential of salivary metabolomics in the detection of oral potentially malignant disorders (OPMDs) and oral cancer (OC). Materials and methods: A systematic review was performed in accordance with the 3rd edition of the Centre for Reviews and Dissemination (CRD) and Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) statement. Electronic searches for articles were carried out in the PubMed, Web of Science, and Scopus databases. The quality assessment of the included studies was evaluated using the Newcastle-Ottawa Quality Assessment Scale (NOS) and the new version of the QUADOMICS tool. Meta-analysis was conducted whenever possible. The effect size was presented using the Forest plot, whereas the presence of publication bias was examined through Begg’s funnel plot. Results: A total of nine studies were included in the systematic review. The metabolite profiling was heterogeneous across all the studies. The expression of several salivary metabolites was found to be significantly altered in OPMDs and OCs as compared to healthy controls. Meta-analysis was able to be conducted only for N-acetylglucosamine. There was no significant difference (SMD = 0.15; 95% CI − 0.25–0.56) in the level of N-acetylglucosamine between OPMDs, OC, and the control group. Conclusion: Evidence for N-acetylglucosamine as a salivary biomarker for oral cancer is lacking. Although several salivary metabolites show changes between healthy, OPMDs, and OC, their diagnostic potential cannot be assessed in this review due to a lack of data. Therefore, further high-quality studies with detailed analysis and reporting are required to establish the diagnostic potential of the salivary metabolites in OPMDs and OC. Clinical relevance: While some salivary metabolites exhibit significant changes in oral potentially malignant disorders (OPMDs) and oral cancer (OC) compared to healthy controls, the current evidence, especially for N-acetylglucosamine, is inadequate to confirm their reliability as diagnostic biomarkers. Additional high-quality studies are needed for a more conclusive assessment of salivary metabolites in oral disease diagnosis. [ABSTRACT FROM AUTHOR]

Objectives: Oral potentially malignant disorders (OPMDs) are the most clinically relevant precursor lesions of the oral squamous cell carcinoma (OSCC). OSCC is one of the 15 most common cancers worldwide. OSCC is with its high rate of mortality an important cause of death worldwide. The diagnosis and therapy of clinically relevant precursor lesions of the OSCC is one of the main parts of prevention of this malignant disease. Targeted therapy is one of the main challenges concerning an oncologically safe tissue removal without overwhelming functional and aesthetic impairment. Materials and methods: In this randomized controlled trial, a newly introduced intraoral 445-nm semiconductor laser (2W; cw-mode; SIROLaser Blue, Dentsply Sirona, Bensheim, Germany) was used in the therapy of OPMDs. Duration and course of wound healing, pain, and scar tissue formation were compared to classical cold blade removal with primary suture by measuring remaining wound area, tissue colorimetry, and visual analogue scale. The study includes 40 patients randomized using a random spreadsheet sequence in two groups (n1 = 20; n2 = 20). Results: This comparative analysis revealed a significantly reduced remaining wound area after 1, 2, and 4 weeks in the laser group compared to the cold blade group (p < 0.05). In the laser group, a significantly reduced postoperative pain after 1 week was measured (p < 0.05). Conclusion: Laser coagulation of OPMDs with the investigated 445-nm semiconductor laser is a safe, gentle, and predictable surgical procedure with beneficial wound healing and reduced postoperative discomfort. Clinical relevance: Compared to the more invasive and bloody cold blade removal with scalpel, the 445-nm semiconductor laser could be a new functional less traumatic tool in the therapy of OPMDs. The method should be further investigated with regard to the identification of further possible indications. Trail registration: German Clinical Trials Register No: DRKS00032626. [ABSTRACT FROM AUTHOR]

Objective: Changes in the autofluorescence of cancerous tissue in comparison to normal tissue due to alteration in the endogenous fluorophores and protein like NAD and FAD has been utilized in various oral cancer screening devices. But potential of fluorescence imaging and spectrometry with exogenous flourorophore has yet to be explored for real time oral cancer detection. Material and methods: In this study, 80 clinically suspicious cases of oral squamous cell carcinoma (OSCC) and oral potentially malignant disorders (OPMDs) were screened with fluorescence imaging and spectrometry device before biopsy. On fluorescence imaging under blue light (480 nm) after application of fluorescein dye application, high fluorescence intensity from the site of lesion in comparison to contralateral normal mucosa was seen. Results: Fluorescence spectra of cancerous tissues and normal tissues show that there was a 4.36 nm of red shift in cancerous tissue. While OPMD tissues showed red shift of 3.42 nm. However, no difference in terms of red shift was found between the OPMD with dysplasia and OPMD without dysplasia. Conclusion: Fluorescence intensity was not helpful in differentiating OPMDs and OSCC cases. Further research is required to explore this optical technique for early detection of precancerous and cancerous lesions.

Abstract Introduction The most effective means for reducing oral cancer (OC) mortality is by preventing late‐stage disease. Early diagnosis can be improved by increasing awareness among healthcare providers, specifically general dental practitioners (GDP). Therefore, our study aimed to assess GDPs' knowledge of OC risk factors and perceived competence in performing conventional oral examination (COE) in routine dental practice. Material and Methods This was a cross‐sectional study conducted in five provinces of Indonesia, namely: Aceh, Banda Aceh (BA); Bandung, West Java (WJ); special district Jakarta (JKT), JKT; Pontianak, West Kalimantan (WK); and Sorong, West Papua (WP). The local Dental Association or Faculty of Dentistry invited the GDPs to attend an education program and complete the survey. Results One hundred seventy‐seven GDPs completed the survey (WJ, n = 63; BA, n = 44, JKT, n = 27; WP, n = 23; and WP, n = 20). A large proportion (164 out of 177, 92.66%) of GDPs felt they had received insufficient training to equip them to diagnose OC and as many as 22.6% (n = 40) did not refer to specialists when they found suspicious mucosal lesions. Notwithstanding the significant regional variations, the majority of Indonesian GDPs self‐reported inadequate knowledge and awareness of OC and scarce confidence in performing COE. Conclusion GDP knowledge of OC risk factors and COE is key to improving early diagnosis of OC at a community level. Therefore, it is suggested that the lack of knowledge and confidence of GDPs reported here should be addressed through the national dental curriculum in Indonesia.

Objectives: We aimed to examine the presence of EBV, EBV strains, and variants among 3 oral conditions including normal oral mucosa (NOM), oral potentially malignant disorders/oral cancer (OPMDs/OC) and non-OPMDs/OC in a group of Thais. Material and methods: Oral exfoliated cells were obtained from 315 participants living in the northeastern and central regions of Thailand. The participants were divided into 3 groups encompassing the NOM, the OPMDs/OC and the non-OPMDs/OC groups. The presence of EBV was first determined by PCR using primers for LMP1 gene. Subsequently, EBV strains of EBNA3c and variants based on LMP1 sequences were determined by real-time PCR. Results: The prevalence of EBV in OPMDs/OC, non-OPMDs/OC and NOM were 72.0 %, 56.2 %, and 27.2 % respectively. EBV type A, B and AB were found in 52.1 %, 32.1 % and 15.8 % of all positive samples, respectively. The percentage of participants with EBV type A was more prominent in the NOM group (72.0 %) compared to the non-OPMDs/OC (54.8 %) and the OPMDs/OC group (41.8 %) whereas EBV type B was higher in the OPMDs/OC group (35.8 %) compared to the non-OPMDs/OC (31.5 %) and the NOM (24.0 %) groups. Regarding EBV variants, 30-bp deletion LMP1 variant (del-LMP1) which is more associated with malignant transformation was predominately found in the OPMDs/OC (32.8 %) and the non-OPMDs/OC (38.4 %) groups compared to the NOM group (20.0 %). Conclusions: High frequency of EBV was demonstrated in the OPMDs/OC group. EBV type A was more predominant in the NOM group whereas EBV type B was more prevalent in the OPMDs/OC group. The del-LMP1 variant was more common in the OPMDs/OC and the non-OPMDs/OC groups.

Oculopharyngeal muscular dystrophy (OPMD) is a rare late-onset muscle disease associated with progressive dysphagia. As there was no patient-reported outcome measure specific for the assessment of dysphagia in OPMD, the Dysphagiameter was developed. The Food and Drug Administration guidance was followed. In Phase 1, a systematic literature review and an expert consultation were conducted to identify the concepts of interest. It was decided that the instrument should assess difficulty swallowing using pictures of foods of various textures (part A) and impact of dysphagia on activities and participation (part B), as defined by the International Classification of Functioning, Disability and Health. In Phase 2, focus groups (n = 3) and online surveys (n = 55) were conducted to generate the items. Then, the food items for part A were selected and grouped into 17 textures by a panel of registered dietitians. Cognitive interviews were conducted (n = 23) to refine the instrument and assess its clarity and comprehensiveness. The final draft included 82 food items assessing the capacity to swallow foods and drinks (part A) and 10 items assessing the impact of dysphagia on activities and participation (part B). Item reduction and assessment of psychometrics properties, using Rasch analysis, are ongoing as part of Phase 3. [ABSTRACT FROM AUTHOR]

Simple Summary: Early diagnosis of potentially malignant oral disorders (OPMD) is crucial in reducing oral cancer mortality. It is necessary to investigate and identify predictive biomarkers capable of estimating the risk of malignant transformation in potentially malignant oral lesions. In this study, we analyzed a panel of salivary markers, including adenosine deaminase (ADA), ferritin (FRR) and total protein (TP). We found no significant differences in salivary ADA between the OPMD group and controls. However, we did observe statistically significant differences in ferritin and total proteins when compared to the control group. Therefore, ferritin and total proteins may serve as potential salivary biomarkers for diagnosis. Furthermore, saliva tests are a reliable and non-invasive diagnostic tool, offering an intriguing alternative for screening large populations. Nevertheless, validation through extensive clinical studies is required. Introduction: Oral potentially malignant disorders (OPMD) are lesions associated with an increased risk of transformation (MT) into cancer. Objective: A study was made of the salivary levels of adenosine deaminase (ADA), ferritin (FRR) and total proteins (TP) in healthy individuals and in patients with oral potentially malignant disorders (OPMD), assessing the potential role of saliva as a diagnostic tool. Methods: A total of 91 subjects participated in the study, divided into two groups—59 patients with OPMD (oral leukoplakia or oral lichen planus) and 32 healthy controls—with measurements being made of salivary ADA, ferritin (FRR) and total proteins (TP). Results: There were no significant differences in salivary mean ADA between the OPMD group 0.85 ± 2.18 UI/I and the controls 0.71 ± 1.72 UI/I (p = 0.934), though the levels of both FRR mean OPMD, 12.66 ± 10.50 (µg/L), versus control, 7.19 ± 4.44 (p = 0.001), and TP, 23.41 ± 17, versus control, 14.15 ± 15.19, were significantly higher in the OPMD group (p = 0.001). Patients with oral lichen planus showed significant differences in terms of FRR (p = 0.009) and TP (p = 0.003). The ferritin in LPO with a cut-off point of 8.5C showed a sensitivity and specificity of 54.3% and 82.3, respectively. The area under the curve (AUC) was 0.69 (95% confidence interval (95% CI): 0.58–0.82; p = 0.003). Conclusions: Ferritin and total proteins may constitute potential salivary biomarkers for oral lichen planus, though further studies are still needed in this field. In addition, saliva testing is a reliable and noninvasive diagnostic tool and appears to be a reliable strategy offering an interesting alternative for the screening of large populations. [ABSTRACT FROM AUTHOR]

Background: Oculo-pharyngeal muscular dystrophy (OPMD) is a rare disease, caused by trinucleotide repeat expansion in the PABPN1 gene, inherited in an autosomal dominant (AD) manner. Its main features are eyelid ptosis and dysphagia, which manifest at the end of the fifth decade of life. Other symptoms include proximal muscle weakness and bulbar muscle weakness. Although OPMD is prevalent worldwide, a higher prevalence has been reported in the Jewish population from Bukhara. Currently, no specific drugs are available for OPMD. Objective: Our National Israeli Registry for Oculo-Pharyngeal Muscular Dystrophy (IsrO-PMD) study aims to provide a framework for the assessment and documentation of the natural history of the diseases as we as a multi-disciplinary management of patients with OPMD. The IsrO-PMD may be the cornerstone of future clinical trials for novel therapies for OPMD. Methods: The IsrO-PMD is a national prospective registry that involves non-interventional data collection based on the Global Rare Diseases Patient Registry (GRDPR) and data repository standard. Inclusion criteria are clinical diagnosis of OPMD and positive genetic testing. Patients who meet inclusion criteria will be examined using a series of multi-disciplinary investigations and questionnaires including periodic follow-up examinations. Specific attention is given to comprehensive neurological, swallowing, and ophthalmological evaluations. Discussion: The establishment of this national registry will enhance our understanding of the natural history of OPMD, establish quality care benchmarks, and develop treatment strategies in addressing the multi-system pathophysiology of the disease and associated comorbidities. Our registry provides a foundation for the use of new cutting-edge treatments as they become available. [ABSTRACT FROM AUTHOR]

OPMDs (oral potentially malignant disorders) are a group of disorders affecting the oral mucosa that are characterized by aberrant cell proliferation and a higher risk of malignant transformation. Vitamin D (VitD) and its receptor (VDR) have been extensively studied for their potential contributions to the prevention and therapeutic management of various diseases and neoplastic conditions, including oral cancer. Observational studies suggest correlations between VitD deficiency and higher cancer risk, worse prognosis, and increased mortality rates. Interestingly, emerging data also suggest a link between VitD insufficiency and the onset or progression of OPMDs. Understanding the role of the VitD–VDR axis not only in established oral tumors but also in OPMDs might thus enable early detection and prevention of malignant transformation. With this article, we want to provide an overview of current knowledge about OPMDs and VitD and investigate their potential association and ramifications for clinical management of OPMDs. [ABSTRACT FROM AUTHOR]

Background: Oral leukoplakia (OLK) is the most studied oral potentially malignant disorders in the scientific literature. Its malignant transformation (MT) rate varies between 1.1% and 40.8%, depending on the type of study and population group studied. There is no universal agreement to treat or manage these lesions, so it is up to each clinician’s experience and expertise in how he/she manages these patients. Objectives: The aim of this retrospective study was to assess the clinical aspects and pattern of evolution of OLK in 30 patients five years or more after the initial diagnosis. Materials and methods: We selected 30 OLK patients from our database. Demographic, clinical and evolutive data was retrieved from the medical files. The following variables were analysed: age and sex, smoking habits, clinical features (form, dimension, site of the lesion), result of mycological examination, treatment and outcomes of the lesions over a follow-up of more than five years. Results: For a follow-up of 119.63 months, we detected a value of 0.2% MT rate per year. Outcomes varied from the complete disappearance of the lesion to recurrence and malignant transformation with a variety of treatment methods applied. Conclusion: Despite the low MT rate for a long follow-up, it is hard to say which treatment method is the best, due to the heterogeneity of the clinical aspects of the lesions and because there is no standardised test method, either genetic testing or immunohistochemical testing. We recommend a varied approach, suitable for each patient's needs and medical context, always when possible histopathological confirmation for grading epithelial dysplasia, which remains the most reliable method of checking the process of malignant transformation. [ABSTRACT FROM AUTHOR]

Alzheimer's disease and related disorders feature neurofibrillary tangles and other neuropathological lesions composed of detergent-insoluble tau protein. In recent structural biology studies of tau proteinopathy, aggregated tau forms a distinct set of conformational variants specific to the different types of tauopathy disorders. However, the constituents driving the formation of distinct pathological tau conformations on pathway to tau-mediated neurodegeneration remain unknown. Previous work demonstrated RNA can serve as a driver of tau aggregation, and RNA associates with tau containing lesions, but tools for evaluating tau/RNA interactions remain limited. Here, we employed molecular interaction studies to measure the impact of tau/RNA binding on tau microtubule binding and aggregation. To investigate the importance of tau/RNA complexes (TRCs) in neurodegenerative disease, we raised a monoclonal antibody (TRC35) against aggregated tau/RNA complexes. We showed that native tau binds RNA with high affinity but low specificity, and tau binding to RNA competes with tau-mediated microtubule assembly functions. Tau/RNA interaction in vitro promotes the formation of higher molecular weight tau/RNA complexes, which represent an oligomeric tau species. Coexpression of tau and poly(A)45 RNA transgenes in Caenorhabditis elegans exacerbates tau-related phenotypes including neuronal dysfunction and pathological tau accumulation. TRC35 exhibits specificity for Alzheimer's disease-derived detergent-insoluble tau relative to soluble recombinant tau. Immunostaining with TRC35 labels a wide variety of pathological tau lesions in animal models of tauopathy, which are reduced in mice lacking the RNA binding protein MSUT2. TRC-positive lesions are evident in many human tauopathies including Alzheimer's disease, progressive supranuclear palsy, corticobasal degeneration and Pick's disease. We also identified ocular pharyngeal muscular dystrophy as a novel tauopathy disorder, where loss of function in the poly(A) RNA binding protein (PABPN1) causes accumulation of pathological tau in tissue from post-mortem human brain. Tau/RNA binding drives tau conformational change and aggregation inhibiting tau-mediated microtubule assembly. Our findings implicate cellular tau/RNA interactions as modulators of both normal tau function and pathological tau toxicity in tauopathy disorders and suggest feasibility for novel therapeutic approaches targeting TRCs. [ABSTRACT FROM AUTHOR]

Malignant and potentially malignant epithelial lesions are often associated with various abnormalities such as epithelial dysplasia, abnormal DNA content, loss of heterozygosity, and chromosomal number aberrations. Screening and early detection of such abnormalities facilitates proper care and also helps to prevent further progression of potentially malignant lesions to malignancy. In such way, the presence of DNA aneuploidy in oral potentially malignant disorders (OPMDs) may serve as an indicator for the malignant transforming potential. Various assessment methods have been proposed to find the DNA ploidy status of cells. This current systematic review is mainly designed to assess the importance of ploidy status in OPMD while measuring the feasibility of using this biomarker for evaluating the hazard of malignant transformation. As an upshot of this systematic review, we can conclude that use of DNA ploidy status can serve as an independent bio-marker for predicting the malignant transformation of lesions. Furthermore, as a future scope the use of DNA ploidy analysis in normal mucosa of smokers will help to assess the malignancy risk and this technique might also help to predict the genetic predisposition of patients with malignancy. [ABSTRACT FROM AUTHOR]

Abstract Background Betel nut chewing plays a role in the pathogenesis of oral submucous fibrosis (OSF) and oral squamous cell carcinoma (OSCC). As the major active ingredient of the betel nut, the effect of arecoline and its underlying mechanism to OSF and OSCC pathogenesis remain unclear. Methods Next-generation sequencing-based transcriptome and dRRBS analysis were performed on OSF and OSCC cells under low-dose arecoline exposure. Functional analyses were performed to compare the different roles of arecoline during OSF and OSCC pathogenesis, and key genes were identified. Results In this study, we identified that low-dose arecoline promoted cell proliferation of both NFs and OSCC cells via the acceleration of cell cycle progression, while high-dose arecoline was cytotoxic to both NFs and OSCC cells. We performed for the first time the transcriptome and methylome landscapes of NFs and OSCC cells under low-dose arecoline exposure. We found distinct transcriptome and methylome profiles mediated by low-dose arecoline in OSF and OSCC cells, as well as specific genes and signaling pathways associated with metabolic disorders induced by low-dose arecoline exposure. Additionally, low-dose arecoline displayed different functions at different stages, participating in the modulation of the extracellular matrix via Wnt signaling in NFs and epigenetic regulation in OSCC cells. After exposure to low-dose arecoline, the node roles of FMOD in NFs and histone gene clusters in OSCC cells were found. Meanwhile, some key methylated genes induced by arecoline were also identified, like PTPRM and FOXD3 in NFs, SALL3 and IRF8 in OSCC cells, indicating early molecular events mediated by arecoline during OSF and OSCC pathogenesis. Conclusions This study elucidated the contribution of low-dose arecoline to OSF and OSCC pathogenesis and identified key molecular events that could be targeted for further functional studies and their potential as biomarkers.

Malignant and potentially malignant epithelial lesions are often associated with various abnormalities such as epithelial dysplasia, abnormal DNA content, loss of heterozygosity, and chromosomal number aberrations. Screening and early detection of such abnormalities facilitates proper care and also helps to prevent further progression of potentially malignant lesions to malignancy. In such way, the presence of DNA aneuploidy in oral potentially malignant disorders (OPMDs) may serve as an indicator for the malignant transforming potential. Various assessment methods have been proposed to find the DNA ploidy status of cells. This current systematic review is mainly designed to assess the importance of ploidy status in OPMD while measuring the feasibility of using this biomarker for evaluating the hazard of malignant transformation. As an upshot of this systematic review, we can conclude that use of DNA ploidy status can serve as an independent bio-marker for predicting the malignant transformation of lesions. Furthermore, as a future scope the use of DNA ploidy analysis in normal mucosa of smokers will help to assess the malignancy risk and this technique might also help to predict the genetic predisposition of patients with malignancy.

Background: Oral potentially malignant disorders (OPMD) are associated with the risk of malignant transformation (MT) into oral cavity carcinoma (OCC). Oral lichen planus (OLP) is one of the most common OPMDs in western countries. Although there is a substantial amount of research on progression to cancer, a specific analysis of the clinical characteristics and prognosis of cancer developed in patients with a history of OLP versus patients without a history of OLP has not been investigated so far. Methods: Retrospective evaluation of 82 patients treated for OCC with a known history of OLP compared to a representative sample of 82 patients treated for OCC without a known history of LP. Comparative analyses were performed on age at presentation, sex, TNM staging, clinical characteristics, pathology characteristics, 2‐ and 5‐year overall survival (OS), and disease‐free survival (DFS). Results: It was shown that patients with a history of LP were significantly younger at first presentation than patients without a history of LP (mean age difference 6.7 years, 95% CI 3.1–10.3, p < 0.05). Also, patients with a history of OLP were in higher proportion females. The main pathological stage at presentation was significantly lower in the OLP group (p < 0.05). The 2‐year survival analysis showed that DFS and OS were significantly lower in patients without a known history of OLP, with a hazard ratio (HR) of 3.1 (95% CI 1.4–6.8) and HR of 2.6 (95% CI 1.3–5.3), respectively. The 5‐year survival analysis showed that DFS and OS were significantly lower in patients without a known history of OLP, with a hazard ratio of 3.1 (95% CI 1.6–6.2) and of 2.9 (95% CI 1.5–5.6), respectively. Conclusions: Cancer arising from OLP has peculiar characteristics compared to cancer in naïve patients. It most commonly affects younger patients, women, and nonsmokers. It is usually diagnosed at earlier stages and appears to have less aggressive behavior at presentation. Moreover, when 2‐ and 5‐year survival is analyzed, it appears that patients in OLP group have an overall and a disease‐free survival advantage. These results suggest that cancer from OLP is less aggressive and thus has a potential biological difference with cancer arising in non‐OLP patients. Further clinical and basic investigations are needed to confirm the results of this study. [ABSTRACT FROM AUTHOR]

Introduction Some oral cancers are preceded by oral potentially malignant disorders (OPMD), clinically and histologically characterized by epithelial dysplasia. Leukoplakia is one of the OPMDs which clinically categorized into homogenous and nonhomogenous. Nonhomogeneous leukoplakia has a higher potential for malignant change. Therefore, dentists are required to recognize leukoplakia early during an oral (visual) examination, and this competency must be one of the requirements before graduation. Objective This study aimed to understand the level of knowledge of the dental undergraduate students about leukoplakia as an OPMD. Methods This research was an observational analytic study using a cross-sectional design. Data were collected via a questionnaire survey conducted using Google Forms. The total score was divided into high (9–12), medium (5–8), and low (0–4). Data were analyzed using SPSS version 25 using comparative analysis Mann–Whitney techniques test. Results A total of 180 dental profession students completed the questionnaire. Of these, 74 (41.40%) respondents were 22 years old, and 146 (81.10%) respondents were female. A high level of knowledge was achieved by 130 (72.20%) respondents, with each revealing 68 respondents from the 2019 batch and 62 from the 2018 batch, 49 (27.20%) respondents with a medium level of knowledge with 26 from the 2018 batch and 23 from the 2019 batch, and 1 respondent (0.60%) from the 2019 batch with a low level of knowledge. The results showed a p -value of 0.211. Conclusion There is no significant difference between the levels of knowledge of dental profession students in Universitas Airlangga batches 2018 and 2019 with regard to leukoplakia as an OPMD. [ABSTRACT FROM AUTHOR]

Oral Potentially Malignant Disorder (OPMD) is a significant concern for clinicians due to the risk of malignant transformation. Oral Squamous Cell Carcinoma (OSCC) is a common type of cancer with a low survival rate, causing over 200,000 new cases globally each year. Despite advancements in diagnosis and treatment, the five-year survival rate for OSCC patients remains under 50%. Early diagnosis can greatly improve the chances of survival. Therefore, understanding the development and transformation of OSCC and developing new diagnostic methods is crucial. The field of oral medicine has been advanced by technological and molecular innovations, leading to the integration of new medical technologies into dental practice. This study aims to outline the potential role of non-invasive imaging techniques and molecular signatures for the early detection of Oral Malignant and Potentially Malignant Disorders.

Oculopharyngeal muscular dystrophy (OPMD) is an autosomal dominant disease characterized by the progressive degeneration of specific muscles. OPMD is due to a mutation in the gene encoding poly(A) binding protein nuclear 1 (PABPN1) leading to a stretch of 11 to 18 alanines at N-terminus of the protein, instead of 10 alanines in the normal protein. This alanine tract extension induces the misfolding and aggregation of PABPN1 in muscle nuclei. Here, using Drosophila OPMD models, we show that the unfolded protein response (UPR) is activated in OPMD upon endoplasmic reticulum stress. Mutations in components of the PERK branch of the UPR reduce muscle degeneration and PABPN1 aggregation characteristic of the disease. We show that oral treatment of OPMD flies with Icerguastat (previously IFB-088), a Guanabenz acetate derivative that shows lower side effects, also decreases muscle degeneration and PABPN1 aggregation. Furthermore, the positive effect of Icerguastat depends on GADD34, a key component of the phosphatase complex in the PERK branch of the UPR. This study reveals a major contribution of the ER stress in OPMD pathogenesis and provides a proof-of-concept for Icerguastat interest in future pharmacological treatments of OPMD.

Background: Betel nut chewing plays a role in the pathogenesis of oral submucous fibrosis (OSF) and oral squamous cell carcinoma (OSCC). As the major active ingredient of the betel nut, the effect of arecoline and its underlying mechanism to OSF and OSCC pathogenesis remain unclear. Methods: Next-generation sequencing-based transcriptome and dRRBS analysis were performed on OSF and OSCC cells under low-dose arecoline exposure. Functional analyses were performed to compare the different roles of arecoline during OSF and OSCC pathogenesis, and key genes were identified. Results: In this study, we identified that low-dose arecoline promoted cell proliferation of both NFs and OSCC cells via the acceleration of cell cycle progression, while high-dose arecoline was cytotoxic to both NFs and OSCC cells. We performed for the first time the transcriptome and methylome landscapes of NFs and OSCC cells under low-dose arecoline exposure. We found distinct transcriptome and methylome profiles mediated by low-dose arecoline in OSF and OSCC cells, as well as specific genes and signaling pathways associated with metabolic disorders induced by low-dose arecoline exposure. Additionally, low-dose arecoline displayed different functions at different stages, participating in the modulation of the extracellular matrix via Wnt signaling in NFs and epigenetic regulation in OSCC cells. After exposure to low-dose arecoline, the node roles of FMOD in NFs and histone gene clusters in OSCC cells were found. Meanwhile, some key methylated genes induced by arecoline were also identified, like PTPRM and FOXD3 in NFs, SALL3 and IRF8 in OSCC cells, indicating early molecular events mediated by arecoline during OSF and OSCC pathogenesis. Conclusions: This study elucidated the contribution of low-dose arecoline to OSF and OSCC pathogenesis and identified key molecular events that could be targeted for further functional studies and their potential as biomarkers. [ABSTRACT FROM AUTHOR]

Simple Summary: TNF-α is of interest in oral squamous cell carcinoma (OSCC), with its demonstrated presence affecting both tumour and stromal inflammatory cells to enhance proliferation and facilitate invasion. TNF-α gene polymorphisms have also been associated with an increased risk for both oral pre-cancer and cancer development. Here we present a review of the current knowledge of the role of TNF-α in the aetiology, pathogenesis, and potential therapy of OSCC. Uncovering the inflammatory mechanisms underpinning initiation, progression, and promotion of oral squamous cell carcinoma (OSCC) development is fundamental to the rational pursuit of targeted therapeutics. Here we present a review of the current knowledge of the role of TNF-α in the aetiology, pathogenesis, and potential therapies with regards to OSCC. TNF-α is worthy of particular attention in OSCC, with its presence demonstrated to enhance cell proliferation and its downregulation demonstrated to inhibit proliferation and migration in other carcinomas in both in vitro and in vivo models and oral cancer patients. Increased TNF-α in the OSCC tumour microenvironment has been demonstrated to favour invasion through promotion of firstly the pro-inflammatory, pro-invasive phenotypes of OSCC cells and secondly its paracrine mechanism mediating recruitment and activation of inflammatory cells. Polymorphisms affecting the gene expression of TNF-α have been strongly associated with an increased risk for oral squamous cell carcinoma. A number of studies have considered TNF-α within biofluids, including saliva and serum, as a potential biomarker for the early detection of OSCC, as well as its staging, differentiation, and prognosis. The broad and multifaceted role that TNF-α plays in many inflammatory states presents an obvious confounder, particularly with demonstrated increased TNF-α levels in common oral disease states. Lastly, biologic agents targeting TNF-α are currently in clinical use for immune-mediated inflammatory rheumatological and gastrointestinal diseases. There is the potential that these biological agents might have an adjunctive role in OSCC prevention and treatment. [ABSTRACT FROM AUTHOR]

Surgical correction of myogenic ptosis is a sophisticated endeavor, as the disease is progressive and the post-operative course is prone to significant complications. We sought to review the literature for repair techniques in different types of myogenic ptosis. A PubMed/MEDLINE literature search of publications pertaining to surgical outcomes of progressive myogenic ptosis repair was performed. Studies included were original retrospective studies with a minimum of four patients. A total of 27 articles were identified and divided by etiology of myogenic ptosis; either chronic progressive external ophthalmoplegia (CPEO), oculopharyngeal muscular dystrophy (OPMD), myasthenia gravis (MG), or mixed. Surgical techniques predominantly involved levator advancement, levator resection, frontalis sling, blepharoplasty, and Fasanella-Servat. Success rates ranged from 60.5% to 100%. Significant postoperative complications included ptosis recurrence, under-correction, over-correction, keratopathy, lagophthalmos, sling exposure, and sling infection. Like surgical repair for other forms of ptosis, correction of progressive myogenic ptosis is guided by levator excursion. However, myogenic ptosis is especially challenging as it is characterized by worsening ptosis and the loss of protective corneal mechanisms. The goals of care with myogenic ptosis involves repairing ptosis just sufficiently to alleviate visual obstruction while avoiding adverse post-operative complications. This intentional under-correction subsequently increases susceptibility for ptosis recurrence. Myogenic ptosis repair therefore requires delicate balancing between function, sustained repair, and corneal protection. [ABSTRACT FROM AUTHOR]

Background/purpose: Oral potentially malignant disorder (OPMD) is an important premalignancy worldwide. MicroRNAs (miRNAs) are endogenously expressed non-coding RNAs that regulate the post-transcriptional levels of targeted mRNAs. MiRNA-375 (miR-375) is markedly downregulated in oral carcinoma tissues and plays an oncogenic role in oral carcinogenesis. We explored the potential of the deregulated salivary miR-375 levels in OPMD patients. Materials and methods: . We analyzed the levels of miR-375 in the saliva of patients with OPMD (n = 45) and healthy controls (n = 24) by quantitative RT-PCR. The cell lysates and supernatants were treated with the miR-375 mimic and inhibitor. Results: Salivary miR-375 levels were decreased markedly in the patients with OPMD, compared with the controls. OPMD patients with non-dysplasia showed a higher abundance of miR-375 in the saliva than dysplasia patients, suggesting that salivary miR-375 is a more sensitive marker for OPMD. Patients with malignant transformation during the follow-up period showed lower expression of saliva miR-375 than the others. MiR-375 expression was markedly decreased by treatment with the miR-375 inhibitor, and the supernatants of both NHOK and SAS cells showed a corresponding decline in miR-375 expression. Conclusion: Our results indicate the potential application of salivary miR-375 as a biomarker for the detection and long-term follow-up of OPMD.

The prevalence of oral human papillomavirus (HPV) in the healthy population and patients with oral diseases such as oral squamous cell carcinoma (OSCC), oral potentially malignant disorders (OPMDs), and oral benign lesions (BL), is not consistently described in the literature, with scarce and often heterogeneous data. In addition, the efficacy of HPV prophylactic vaccines in preventing HPV-related oral disorders has been scarcely investigated. The prevalence of HPV and the potential impact of vaccines were analyzed in 1,415 oral rinse specimens, collected over 10 years and grouped into four categories based on histological/clinical diagnosis. HPV prevalence in OSCC, OPMD, and BL patients and in healthy individuals potentially exposed to HPV (HPE) was comparable (12.7 vs. 27.2% vs. 13.5 vs. 9%). Statistical analysis of the vaccine impact involved calculating high and low estimates and showed a significant difference only for the low effect. The nonavalent vaccine had higher low estimates than the bivalent vaccine in OSCC and HPE patients (29.6 vs. 51.9%, p <0.05; 18.2 vs. 42.4%, p <0.05), while for OPMD and BL, the frequency of bivalent low estimates was lower than that of quadrivalent and nonavalent (48.6 vs. 68.6%, p <0.05 and 48.6 vs. 77.1%, p <0.05; 23.9 vs. 50.7%, p <0.05, and 23.9 vs. 63.4%, p <0.05). This study provided new insights into the prevalence of oral HPV and showed that the nonavalent vaccine may provide better protection than the other vaccines in the presence of an OSCC diagnosis. Conversely, the quadrivalent vaccine may be sufficient to prevent OPMD and BL. [ABSTRACT FROM AUTHOR]

Aims: The present study evaluated the frequency of micronuclei in oral potentially malignant disorders (OPMDs) and their association with the presence of dysplasia on cytology and biopsy as well as their association with p53 mutation and p16 expression. Cytological findings of dysplastic changes in OPMDs were compared to histological diagnoses. Material and Methods: This was a cross-sectional, observational, descriptive study. Scrape smears (n = 74) were collected from lesions in patients with OPMDs. Punch biopsy was collected in patients showing dysplastic changes. Tissue microarray for p53 mutation and p16 expression was performed using paraffin embedded blocks. Cases were classified into grades of dysplasia using both scrape smears and biopsy. Micronuclei frequency was calculated per 100 cells using scrape smears. Mann–Whitney U test was used for correlation of cytology and histology for grade of dysplasia as well as micronuclear frequency with p53 mutation and p16 expression. Results: Micronuclear frequency was found to be increased in patients with dysplasia. A significant association of micronuclear frequency with dysplastic changes was seen on cytology. Sensitivity of cytological evaluation was found to be 64.7%. The association of the micronuclear frequency of samples with p53 mutation and p16 expression was nearly significant (n = 28, P = 0.069 and 0.095, respectively). Conclusion: Micronuclear frequency can be a reliable marker of mutagenic change in OPMDs. Cytological assessment of micronuclei can serve as useful, non-invasive, and relatively inexpensive tool to predict cancerous changes in OPMDs.

Oculopharyngeal muscular dystrophy (OPMD) is a rare muscle disease characterized by an onset of weakness in the pharyngeal and eyelid muscles. The disease is caused by the extension of a polyalanine tract in the Poly(A) Binding Protein Nuclear 1 (PABPN1) protein leading to the formation of intranuclear inclusions or aggregates in the muscle of OPMD patients. Despite numerous studies stressing the deleterious role of nuclear inclusions in cellular and animal OPMD models, their exact contribution to human disease is still unclear. In this study, we used a large and unique collection of human muscle biopsy samples to perform an in-depth analysis of PABPN1 aggregates in relation to age, genotype and muscle status with the final aim to improve our understanding of OPMD physiopathology. Here we demonstrate that age and genotype influence PABPN1 aggregates: the percentage of myonuclei containing PABPN1 aggregates increases with age and the chaperone HSP70 co-localize more frequently with PABPN1 aggregates with a larger polyalanine tract. In addition to the previously described PRMT1 and HSP70 co-factors, we identified new components of PABPN1 aggregates including GRP78/BiP, RPL24 and p62. We also observed that myonuclei containing aggregates are larger than myonuclei without. When comparing two muscles from the same patient, a similar amount of aggregates is observed in different muscles, except for the pharyngeal muscle where fewer aggregates are observed. This could be due to the peculiar nature of this muscle which has a low level of PAPBN1 and contains regenerating fibers. To confirm the fate of PABPN1 aggregates in a regenerating muscle, we generated a xenograft model by transplanting human OPMD muscle biopsy samples into the hindlimb of an immunodeficient mouse. Xenografts from subjects with OPMD displayed regeneration of human myofibers and PABPN1 aggregates were rapidly present—although to a lower extent-after muscle fiber regeneration. Our data obtained on human OPMD samples add support to the dual non-exclusive models in OPMD combining toxic PABPN1 intranuclear inclusions together with PABPN1 loss of function which altogether result in this late-onset and muscle selective disease. [ABSTRACT FROM AUTHOR]

Background: Oral squamous cell carcinoma (OSCC) is the most common malignancy in India. Majority of OSCC occurs in relation to various oral potentially malignant disorders (OPMD). Most patients report in advanced stages due to lack of awareness and delay in biopsy. Immunohistochemistry (IHC) could be used to identify the genetic alterations influencing proliferation and apoptosis that accumulate in OPMD and may transform it into OSCC. Bcl2 is one such molecule that enhances cell survival and reduces apoptosis. Aims & Objectives: Our study aimed to determine and compare the expression of Bcl-2 in OPMD and OSCC. Materials and methods: 70 samples were retrieved from the department archives including 10 normal mucosa, 30 cases of OPMD and 30 cases of OSCC. The number of Bcl-2 positive cells was counted in 50 cells of each field by two independent observers. Cases were assigned to one of the following categories: 0% positive cells (-), 10% positive cells (+), 10-25% positive cells (++), 26-50% positive cells (+++) or more than 50% positive cells (++++). They were scored as: 0% positive cells (-), 10% positive cells (+), 10-25% positive cells (++), 26-50% positive cells (+++) or more than 50% positive cells (++++). The data were tabulated and analyzed using CROSSTABS procedures, Mean ± SD, Mann-Whitney's U-test and Chi Square test using SPSS 15.0 (SPSS INC, Chicago, IL). Results: Mean Bcl-2 expression in 10 Normal Mucosa (N) samples with the Mean values of 0.0824 with the Standard Deviation values of 0.127. In 30 OPMD samples the Mean value was 0.0397 with the Standard Deviation value of 0.083 and in the 30 OSCC samples the Mean value was 0.0301 with the Standard Deviation value of 0.060. Summary: We found increased Bcl2 expression in basal and parabasal cells of normal epithelium but progressive decrease in its expression in OPMD and in OSCC. Though our study did not achieve statistical significance, multi-centre studies on this expression will be helpful to understand the role of this anti-apoptotic molecule. [ABSTRACT FROM AUTHOR]

Background: Exercise is widely considered to have beneficial impact on skeletal muscle aging. In addition, there are also several studies demonstrating a positive effect of exercise on muscular dystrophies. Oculopharyngeal muscular dystrophy (OPMD) is a late-onset autosomal dominant inherited neuromuscular disorder caused by mutations in the PAPBN1 gene. These mutations consist in short (1-8) and meiotically stable GCN trinucleotide repeat expansions in its coding region responsible for the formation of PAPBN1 intranuclear aggregates. This study aims to characterize the effects of two types of chronic exercise, resistance and endurance, on the OPMD skeletal muscle phenotype using a relevant murine model of OPMD., Methods: In this study, we tested two protocols of exercise. In the first, based on endurance exercise, FvB (wild-type) and A17 (OPMD) mice underwent a 6-week-long motorized treadmill protocol consisting in three sessions per week of running 20 cm/s for 20 min. In the second protocol, based on resistance exercise generated by chronic mechanical overload (OVL), surgical removal of gastrocnemius and soleus muscles was performed, inducing hypertrophy of the plantaris muscle. In both types of exercise, muscles of A17 and FvB mice were compared with those of respective sedentary mice. For all the groups, force measurement, muscle histology, and molecular analyses were conducted., Results: Following the endurance exercise protocol, we did not observe any major changes in the muscle physiological parameters, but an increase in the number of PABPN1 intranuclear aggregates in both tibialis anterior (+24%, **P = 0.0026) and gastrocnemius (+18%, ****P < 0.0001) as well as enhanced collagen deposition (+20%, **P = 0.0064 in the tibialis anterior; +35%, **P = 0.0042 in the gastrocnemius) in the exercised A17 OPMD mice. In the supraphysiological resistance overload protocol, we also observed an increased collagen deposition (×2, ****P < 0.0001) in the plantaris muscle of A17 OPMD mice which was associated with larger muscle mass (×2, ****P < 0.0001) and fibre cross sectional area (×2, ***P = 0.0007) and increased absolute maximal force (×2, ****P < 0.0001) as well as a reduction in PABPN1 aggregate number (-16%, ****P < 0.0001)., Conclusions: Running exercise and mechanical overload led to very different outcome in skeletal muscles of A17 mice. Both types of exercise enhanced collagen deposition but while the running protocol increased aggregates, the OVL reduced them. More importantly OVL reversed muscle atrophy and maximal force in the A17 mice. Our study performed in a relevant model gives an indication of the effect of different types of exercise on OPMD muscle which should be further evaluated in humans for future recommendations as a part of the lifestyle of individuals with OPMD., (© 2024 The Author(s). Journal of Cachexia, Sarcopenia and Muscle published by Wiley Periodicals LLC.)

Oral cancer is the most common cancer among males in the Sri Lankan population. The aim of this study was to assess the health seeking behaviors and associated factors for OPMD.A hospital based descriptive cross-sectional study was conducted among Out Patients Department attendees of the Institute of Oral Health, Maharagama, from July 1, 2018 to December 31, 2019 by administering a questionnaire followed by an intra oral examination.The total number of 110 OPMD/oral cancer patients were identified. Awareness on OPMD was that 40 ​%. Majority were unaware of the danger of areca nut and alcohol use. Out of the identified cases during oral examination, 47.3 ​% were incidental findings while only 7.3 ​% were referred by the General Medical Practitioners (GMP). None were referred by the Primary Health Care (PHC) staff.The level of awareness on OPMD and its risk factors were very low. Incidental findings during the dental screening being the main mode of detection of OPMD, highlights the importance of conducting opportunistic screening at dental settings. Implementation of the Risk Factor Model (RFM) approach for the early detection of oral cancer through PHC staff and GMP is validated to encourage more early referrals.

Oral potentially malignant disorders (OPMDs) are a group of conditions that carry a risk of oral squamous cell carcinoma (OSCC) development. Recent studies indicate that periodontal disease-associated pathogenic bacteria may play a role in the transition from healthy mucosa to dysplasia and to OSCC. Yet, the microbial signatures associated with the transition from healthy mucosa to dysplasia have not been established. To characterize oral microbial signatures at these different sites, we performed a 16S sequencing analysis of both oral swab and formalin-fixed, paraffin-embedded tissue (FFPE) samples. We collected oral swabs from healthy mucosa (from healthy patients), histologically normal mucosa adjacent to dysplasia, and low-grade oral dysplasia. Additionally, FFPE samples from histologically normal mucosa adjacent to OSCC, plus low grade and high-grade oral dysplasia samples were also collected. The collected data demonstrate significant differences in the alpha and beta microbial diversities of different sites in oral mucosa, dysplasia, and OSCC, as well as increased dissimilarities within these sites. We found that the Proteobacteria phyla abundance increased, concurrent with a progressive decrease in the Firmicutes phyla abundance, as well as altered levels of Enterococcus cecorum, Fusobacterium periodonticum, Prevotella melaninogenica, and Fusobacterium canifelinum when moving from healthy to diseased sites. Moreover, the swab sample analysis indicates that the oral microbiome may be altered in areas that are histologically normal, including in mucosa adjacent to dysplasia. Furthermore, trends in specific microbiome changes in oral swab samples preceded those in the tissues, signifying early detection opportunities for clinical diagnosis. In addition, we evaluated the gene expression profile of OSCC cells (HSC-3) infected with either P. gingivalis, T. denticola, F. nucelatum, or S. sanguinis and found that the three periodontopathogens enrich genetic processes related to cancer progression, including skin keratinization/cornification, while the commensal enriched processes related to RNA processing and adhesion. Finally, we reviewed the dysplasia microbiome literature and found a significant decrease in commensal bacteria, such as the Streptococci genus, and a simultaneous increase in pathogenic bacteria, mainly Bacteroidetes phyla and Fusobacterium genus. These findings suggest that features of the oral microbiome can serve as novel biomarkers for dysplasia and OSCC disease progression.

Dentists, especially those who are not oral lesion specialists and live in rural areas, need an artificial intelligence (AI) system for accurately assisting them in screening for oral cancer that may appear in smartphone images. Not many literatures present a viable model that addresses the needs, especially in the context of oral lesion segmentation in smartphone images. This study demonstrates the use of a deep learning-based AI for simultaneously identifying types of oral cancer lesions as well as precisely outlining the boundary of the lesions in the images for the first time. The lesions of interest were oral potentially malignant disorders (OPMDs) and oral squamous cell carcinoma (OSCC) lesions. The model could successfully (1) detect if the images contained the oral lesions, (2) determine types of the lesions, and (3) precisely outline the boundary of the lesions. With future success of our project, patients will be diagnosed and treated early before the precancer lesions can progress into deadly cancerous ones. [ABSTRACT FROM AUTHOR]

Objective: Dysphagia can be troublesome in sporadic inclusion body myositis (sIBM) and oculopharyngeal muscular dystrophy (OPMD), but no established treatment exists. Cricopharyngeal muscle botulinum toxin injection has at case level been reported to be effective. We evaluated safety and efficacy of botulinum toxin injections in the cricopharyngeal muscle in patients with dysphagia due to sIBM or OPMD. Methods: Participants were included from our outpatient clinic. Cricopharyngeal constriction was confirmed by laryngoscopy. After EMG confirmation of needle placement in the cricopharyngeal muscle, botulinum toxin A was injected in awake patients. An individualized dose of 5–10 units of botulinum toxin A was applied initially and titrated up a maximum of 3 times. Outcome measures were change in dysphagia questionnaire, timed cold-water swallow test and subjective dysphagia status (worse, unchanged, improved). Due to the need for individualized dosing and a limited number of available patients, an uncontrolled, un-blinded design was used. Results: Thirteen patients, 3 with OPMD, received at least 1 injection. In the dysphagia questionnaire, all but 2 subjects, none with subjective worsening, improved (p < 0.001). Subjectively, seven felt an improvement, 4 no change and 2 a worsening. No overall change was seen the timed cold-water swallow test. No serious adverse events were observed. Conclusion: Botulinum toxin injection of the cricopharyngeal muscle in patients with OPMD and sIBM had a beneficial effect on dysphagia in most of the treated patients. Two of 13 patients experienced a temporary worsening not reflected in dysphagia score. Limitations are the un-blinded and un-randomized design and subjective assessments methods. Prospective trial registration: EudraCT-number: 2014-002210-23. [ABSTRACT FROM AUTHOR]

In this paper, a unified M-estimation method in Yang (2018) is extended to the matrix exponential spatial dynamic panel specification (MESDPS) with fixed effects in short panels. Similar to the STLE model which includes the spatial lag effect, the space-time effect and the spatial error effect in Yang (2018), the quasi-maximum likelihood (QML) estimation for MESDPS also has the initial condition specification problem. The initial-condition free M-estimator in this paper solves this problem and is proved to be consistent and asymptotically normal. An outer product of martingale difference (OPMD) estimator for the variance-covariance (VC) matrix of the M-estimator is also derived and proved to be consistent. The finite sample property of the M-estimator is studied through an extensive Monte Carlo study. The method is applied to US outward FDI data to show its validity. [ABSTRACT FROM AUTHOR]

Oculopharyngeal muscular dystrophy (OPMD) is a rare autosomal dominant disease that results from an alanine expansion in the N-terminal domain of Poly-A Binding Protein Nuclear-1 (PABPN1). We have recently demonstrated that a two-vector gene therapy strategy significantly ameliorated the pathology in a mouse model of OPMD. This approach entailed intramuscular injection of two recombinant adeno-associated viruses (AAVs), one expressing three short hairpin RNAs (shRNAs) to silence both mutant and wild-type PABPN1 and one expressing a codon-optimized version of PABPN1 that is insensitive to RNA interference. Here we report the continued development of this therapeutic strategy by delivering “silence and replace” sequences in a single AAV vector named BB-301. This construct is composed of a modified AAV serotype 9 (AAV9) capsid that expresses a unique single bifunctional construct under the control of the muscle-specific Spc5-12 promoter for the co-expression of both the codon-optimized PABPN1 protein and two small inhibitory RNAs (siRNAs) against PABPN1 modeled into microRNA (miRNA) backbones. A single intramuscular injection of BB-301 results in robust inhibition of mutant PABPN1 and concomitant replacement of the codon-optimized PABPN1 protein. The treatment restores muscle strength and muscle weight to wild-type levels as well as improving other physiological hallmarks of the disease in a mouse model of OPMD.

Introduction: The diagnosis of and risks associated with oral potentially malignant disorders (OPMD) have been widely reported, but little has been published on the management of OPMDs in a primary dental care setting. Hospital services face ongoing pressures due to long-term follow-up, with a need for surveillance to be jointly undertaken with primary dental care clinicians. In a primary care setting, identification and surveillance of OPMDs can be challenging as no universal guidance exists on recommended recall intervals. Corpus: In this article, an update on OPMDs is provided and, based on the practices of six Oral Medicine units in Europe (London (United Kingdom), Milan (Italy), Bordeaux (France), Porto (Portugal), Zagreb (Croatia) and Santiago de Compostela (Spain)), aiming to provide guidance on monitoring in a primary care setting in Europe. Conclusion: Oral medicine clinicians can provide guidance to general dental practitioners (GDPs) on recommended recall intervals. It is important that they feel confident in monitoring these conditions and, when concerned, to arrange referral to a hospital or appropriate specialist. GDPs should document descriptions of lesions and, if possible, take clinical photographs. Patients should be counselled on modifiable lifestyle factors and directed to oral medicine society websites to access patient information leaflets. [ABSTRACT FROM AUTHOR]